WO2024120517A1 - 特异性结合rsv的抗体 - Google Patents

特异性结合rsv的抗体 Download PDF

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WO2024120517A1
WO2024120517A1 PCT/CN2023/137389 CN2023137389W WO2024120517A1 WO 2024120517 A1 WO2024120517 A1 WO 2024120517A1 CN 2023137389 W CN2023137389 W CN 2023137389W WO 2024120517 A1 WO2024120517 A1 WO 2024120517A1
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seq
cdr
amino acid
acid sequence
antibody
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French (fr)
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徐晓昱
曹林
王祥喜
徐灵杰
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南京诺唯赞生物科技股份有限公司
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A61K39/42—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum viral
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/08—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from viruses
    • C07K16/10—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from viruses from RNA viruses
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/74—Vectors or expression systems specially adapted for prokaryotic hosts other than E. coli, e.g. Lactobacillus, Micromonospora
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/80—Vectors or expression systems specially adapted for eukaryotic hosts for fungi
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/80—Vectors or expression systems specially adapted for eukaryotic hosts for fungi
    • C12N15/81—Vectors or expression systems specially adapted for eukaryotic hosts for fungi for yeasts
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/10—Cells modified by introduction of foreign genetic material

Definitions

  • the present invention provides a group of antibodies or antigen-binding fragments thereof that specifically bind to RSV.
  • the present invention also provides polynucleotides encoding the antibodies or antigen-binding fragments thereof, vectors comprising the polynucleotides, host cells comprising the vectors, methods for generating the antibodies, and compositions comprising the antibodies.
  • Respiratory syncytial virus causes approximately 33 million cases of acute lower respiratory tract infections and more than 100,000 deaths each year in children under the age of 5, and approximately 7.2 deaths per 100,000 people per year in adults over the age of 65.
  • RSV infection does not produce permanent immunity and cannot protect children from reinfection.
  • RSV has become one of the most important pathogens causing acute lower respiratory tract infections in children under the age of 5 and in people with memory and immunodeficiency in the elderly over the age of 65 worldwide, and has become a recognized global health issue.
  • RSV is a non-segmented single-stranded negative-sense RNA virus belonging to the Paramyxoviridae family and the Pneumovirus genus.
  • RSV virus particles contain an envelope.
  • the virus particle is composed of an envelope, a nucleocapsid, and a core.
  • the RSV genome is 15.2 kb in length, transcribes 10 genes (NS1, NS2, N, P, M, SH, G, F, M2, and L from the 3' end to the 5' end), and encodes 11 proteins.
  • M2 contains two open reading frames, encoding two proteins, M2-1 and M2-2; each of the remaining genes encodes one protein.
  • NS1 and NS2 are non-structural proteins
  • N nucleocapsid protein
  • P phosphoprotein
  • L polymerase subunit protein
  • M, M2-1, and M2-2 matrix proteins
  • F fusion protein
  • G adhesion protein
  • SH small hydrophobic protein
  • the G protein and F protein on the surface of RSV virus particles mediate the adsorption and fusion between the virus and host cells, and between virus-infected cells and uninfected cells. They are also the main protective antigens of RSV and can induce the body to produce protective neutralizing antibodies.
  • the F protein has high variability between the two subtypes, and it induces the body to produce type-specific neutralizing antibodies, which do not have a broad protective effect.
  • the F protein is a highly conserved protein.
  • the protective antibodies it induces are broad-spectrum neutralizing antibodies that can simultaneously inhibit RSV infection by RSVA and B. It is an effective target protein for potential RSV preventive and therapeutic drugs and vaccine research.
  • the F protein is active only after being cut into two fragments, F1 (48kDa) and F2 (26kDa), by host proteases.
  • the F protein generally forms a trimer structure of the F1-F2 heterodimer to perform its fusion function.
  • On the F protein it is currently believed that there are 6 epitopes that can produce neutralizing antibodies, namely the epitopes I, II, III, IV and V.
  • the present invention provides an antibody or antigen-binding fragment thereof that specifically binds to RSV, comprising:
  • CDR-H1 as set forth in SEQ ID NO: 1, CDR-H2 as set forth in SEQ ID NO: 2, CDR-H3 as set forth in SEQ ID NO: 3, CDR-L1 as set forth in SEQ ID NO: 4, CDR-L2 as set forth in SEQ ID NO: 5, and CDR-L3 as set forth in SEQ ID NO: 6;
  • CDR-H1 as set forth in SEQ ID NO: 113
  • CDR-H2 as set forth in SEQ ID NO: 114
  • CDR-H3 as set forth in SEQ ID NO: 115
  • CDR-L1 as set forth in SEQ ID NO: 116
  • CDR-L2 as set forth in SEQ ID NO: 117
  • CDR-L3 as set forth in SEQ ID NO: 118;
  • CDR-H1 as set forth in SEQ ID NO: 121
  • CDR-H2 as set forth in SEQ ID NO: 122
  • CDR-H3 as set forth in SEQ ID NO: 123
  • CDR-L1 as set forth in SEQ ID NO: 124
  • CDR-L2 as set forth in SEQ ID NO: 125
  • CDR-L3 as set forth in SEQ ID NO: 126;
  • the antibody or antigen-binding fragment thereof of the invention comprises:
  • VH as shown in SEQ ID NO: 7 and VL as shown in SEQ ID NO: 8;
  • VH as shown in SEQ ID NO: 63 and VL as shown in SEQ ID NO: 64;
  • VH as shown in SEQ ID NO: 119 and VL as shown in SEQ ID NO: 120;
  • VH as shown in SEQ ID NO: 127 and VL as shown in SEQ ID NO: 128;
  • the antibody or antigen-binding fragment thereof of the invention comprises:
  • the antibody or antigen-binding fragment thereof of the present invention comprises an alpha heavy chain, a delta heavy chain, an epsilon heavy chain, a gamma heavy chain or a mu heavy chain.
  • the antibody or antigen-binding fragment thereof of the present invention belongs to the IgG1, IgG2, IgG3 or IgG4 subclass.
  • the antibody or antigen-binding fragment thereof of the present invention comprises a lambda light chain or a kappa light chain.
  • the antibody or antigen-binding fragment thereof of the present invention is a full-length antibody.
  • the antibody or antigen-binding fragment thereof of the present invention is an antibody fragment selected from Fv, scFv, Fab, Fab', F(ab') 2 and xFab. In one embodiment, the antibody or antigen-binding fragment thereof of the present invention is a chimeric antibody or a human antibody or antigen-binding fragment thereof.
  • the antibody or antigen-binding fragment thereof of the invention has one or more of the following properties:
  • (2) is capable of specifically binding to RSV A2 pre-F protein with an EC50 value of less than 62, 61, 60, 59, 50, 40, 36, 35, 32, 31, 30, 29, 25, 24, 23, 22, 21, 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7.5, or 7.2 ng/mL, or with an EC50 value that is less than (e.g., 1% to 99%, such as at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100%) than the EC50 value of MEDI8897;
  • (3) is capable of specifically binding to RSV A2 pre-F protein with a KD value of less than 3.3, 2.2, 1.3, 1.0, 0.9, 0.4, 0.3, 0.2, 0.15, 0.07, 0.06, or 0.001 nM, or with a KD value that is less than the KD value of MEDI8897 (e.g., 1% to 99%, such as at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100%);
  • RSV e.g., type A and/or type B
  • a RSV type A strain capable of inhibiting infection of a host cell by a RSV type A strain (e.g., A2) with an IC50 value of less than 100, 90, 80, 70, 60, 50, 45, 40, 35, 30, 25, 20, 15, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1.5 ng/mL, or with an IC50 value that is less than the IC50 value of MEDI8897 (e.g., 1% to 99%, such as at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100%);
  • (6) capable of inhibiting infection of a host cell by a RSV type B strain (e.g., B9320) with an IC50 value of less than 160, 150, 140, 130, 120, 110, 100, 90, 80, 70, 60, 50, 40, 30, 20, 15, 10, 9, 8, 7, 6, 5, 4, or 3 ng/mL, or with an IC50 value that is less than the IC50 value of MEDI8897 (e.g., 1% to 99%, such as at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100%);
  • a RSV type B strain e.g., B9320
  • a RSV type B strain capable of inhibiting infection of host cells by a RSV type B strain (e.g., B18537) with an IC50 value of less than 80, 70, 60, 50, 45, 40, 35, 30, 20, 15, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 ng/mL, or with an IC50 value that is less than the IC50 value of MEDI8897 (e.g., 1% to 99%, such as at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100%);
  • (9) is capable of inhibiting the binding of MEDI8897 to RSV A2 pre-F protein by 1% to 100%, for example, by at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%;
  • (10) can compete with or inhibit the binding of MK-1654 to RSV A2 pre-F protein
  • (11) is capable of inhibiting the binding of MK-1654 to RSV A2 pre-F protein by 1% to 100%, for example, by at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%;
  • (13) capable of inhibiting the binding of Motavizumab to RSV A2 pre-F protein by 1% to 100%, for example, by at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%;
  • the present invention provides a polynucleotide encoding an antibody or antigen-binding fragment thereof of the present invention.
  • the polynucleotide of the invention comprises:
  • the present invention provides a vector comprising a polynucleotide of the present invention.
  • the present invention provides a host cell comprising a polynucleotide or vector of the present invention.
  • the host cell is a eukaryotic cell.
  • the host cell is a CHO cell.
  • the present invention provides a method for producing an antibody or an antigen-binding fragment thereof, comprising:
  • the invention provides a composition comprising an antibody or antigen-binding fragment thereof of the invention.
  • the invention provides an antibody or antigen-binding fragment thereof or a composition of the invention for use as a medicament.
  • the present invention provides an antibody or antigen-binding fragment thereof or a composition of the present invention for use in treating a disease.
  • the disease is a lower respiratory tract infection.
  • the disease is a disease caused by RSV infection.
  • the present invention provides the use of the antibody or antigen-binding fragment thereof or the composition of the present invention for the manufacture of a medicament for treating a disease.
  • the disease is a lower respiratory tract infection.
  • the invention provides a method of treating a disease in an individual, comprising administering to the individual a therapeutically effective amount of an antibody or antigen-binding fragment thereof or composition of the invention.
  • the disease is a lower respiratory tract infection.
  • Figure 1-1 and Figure 1-2 show the antigen binding curves (ELISA) of the antibodies of the present invention.
  • Figure 2-1 and Figure 2-2 show the antigen binding curves (BA) of the antibodies of the present invention.
  • Figure 3-1 and Figure 3-2 show the virus neutralization curves of the antibodies of the present invention.
  • FIG4 shows a schematic diagram of a competitive binding epitope assay for the antibodies of the present invention.
  • acceptor human framework refers to a framework comprising a light chain variable domain (VL) framework or a heavy chain variable domain (VH) framework amino acid sequence derived from a human immunoglobulin framework or a human consensus framework as defined below.
  • the acceptor human framework "derived” from a human immunoglobulin framework or a human consensus framework can include the same amino acid sequence, or it can contain amino acid sequence changes. In some embodiments, the number of amino acid changes is 10 or less, 9 or less, 8 or less, 7 or less, 6 or less, 5 or less, 4 or less, 3 or less, or 2 or less.
  • the VL acceptor human framework is identical in sequence to the VL human immunoglobulin framework sequence or the human consensus framework sequence.
  • Binding affinity refers to the strength of the sum of all non-covalent interactions between a single binding site of a molecule (e.g., an antibody) and its binding partner (e.g., an antigen).
  • binding affinity refers to the intrinsic binding affinity that reflects a 1:1 interaction between members of a binding pair (e.g., an antibody and an antigen).
  • the affinity of a molecule X for its partner Y can generally be expressed in terms of a dissociation constant (Kd). Affinity can be measured by common methods known in the art, including those described herein. Specific illustrative and exemplary embodiments for measuring binding affinity are described below.
  • An “affinity matured” antibody is one with one or more alterations in one or more hypervariable regions (HVRs) which result in an improvement in the affinity of the antibody for antigen, compared to a parent antibody which does not possess such alteration(s).
  • HVRs hypervariable regions
  • anti-RSV antibody and "antibody that binds to RSV” refer to antibodies that can bind to RSV with sufficient affinity so that the antibody can be used as a diagnostic, prophylactic and/or therapeutic agent for targeting RSV.
  • the extent to which an anti-RSV antibody binds to an unrelated, non-RSV protein is less than about 10% of the binding of the antibody to RSV, as measured, for example, by radioimmunoassay (RIA).
  • an antibody that binds to RSV has a dissociation constant (Kd) of ⁇ 1 ⁇ M, ⁇ 100 nM, ⁇ 10 nM, ⁇ 1 nM, ⁇ 0.1 nM, ⁇ 0.01 nM, or ⁇ 0.001 nM (e.g., 10 -8 M or less, e.g., 10 -8 M to 10 -13 M, e.g., 10 -9 M to 10 -13 M).
  • Kd dissociation constant
  • nM e.g. 10 -8 M or less, e.g., 10 -8 M to 10 -13 M, e.g., 10 -9 M to 10 -13 M.
  • “anti-RSV antibody” and "antibody that binds to RSV” refer to antibodies that can bind to RSV with sufficient affinity so that the antibody can be used as a diagnostic, prophylactic and/or therapeutic agent for targeting RSV.
  • an anti-RSV antibody binds to an unrelated, non-RSV protein is less than about 10% of the binding of the antibody to RSV, as measured, for example, by radioimmunoassay (RIA).
  • an antibody that binds to RSV has a dissociation constant (Kd) of ⁇ 1 ⁇ M, ⁇ 100 nM, ⁇ 10 nM, ⁇ 1 nM, ⁇ 0.1 nM, ⁇ 0.01 nM, or ⁇ 0.001 nM (e.g., 10 -8 M or less, e.g., 10 -8 M to 10 -13 M, e.g., 10 -9 M to 10 -13 M).
  • Antibodies that bind to RSV are “anti-RSV pre-F antibodies” and “antibodies that bind to RSV pre-F”, particularly “anti-RSV A2 pre-F antibodies” and “antibodies that bind to RSV A2 pre-F”.
  • the anti-RSV antibody binds to a pre-F epitope that is conserved among different RSV strains.
  • anti-RSV antibodies refer to antibodies that specifically bind to RSV or its antigens or epitopes thereof with a binding affinity of 1.0 x 10-8 mol/l or less, in one embodiment, a KD value of 1.0 x 10-9 mol/l or less, and in one embodiment, a KD value of 1.0 x 10-9 mol/l to 1.0 x 10-13 mol/l.
  • binding affinity is measured using standard binding assays, such as surface plasmon resonance technology ( GE-Healthcare Uppsala, Sweden; SARTORIUS, R8), for example using RSV A2 pre-F protein.
  • antibody herein is used in the broadest sense and encompasses various antibody structures, including but not limited to monoclonal antibodies, polyclonal antibodies, multispecific antibodies (eg, bispecific antibodies), and antibody fragments, so long as they exhibit the desired antigen-binding activity.
  • Antibody fragment refers to a molecule different from an intact antibody, which comprises a portion of an intact antibody that binds to the antigen to which the intact antibody binds.
  • Examples of antibody fragments include, but are not limited to, Fv, Fab, Fab', Fab'SH, F(ab') 2 , xFab; diabodies; linear antibodies; single-chain antibody molecules (e.g., scFv); and multispecific antibodies formed from antibody fragments.
  • epitope means a site on an antigen (either proteinaceous or non-proteinaceous) that is bound by anti-RSV antibodies.
  • An epitope can be formed from a continuous amino acid string (linear epitope) or comprise non-continuous amino acids (conformational epitope), for example, due to the folding of the antigen (i.e., by the tertiary folding of proteinaceous antigens) and become spatially close.
  • Linear epitopes are typically still bound by anti-RSV antibodies after proteinaceous antigens are exposed to denaturants, and conformational epitopes are typically destroyed after being treated with denaturants.
  • the epitope comprises at least 3, at least 4, at least 5, at least 6, at least 7, or 8-10 amino acids in a unique spatial conformation.
  • Screening for antibodies that bind to a specific epitope can be performed using routine methods in the art, such as, for example, but not limited to, alanine scanning, peptide blotting (see Meth. Mol. Biol. 248 (2004) 443-463), peptide cleavage analysis, epitope excision, epitope extraction, chemical modification of antigens (see Prot. Sci. 9 (2000) 487-496), and cross-blocking (see “Antibodies,” Harlow and Lane (Cold Spring Harbor Press, Cold Spring Harb., NY)).
  • Antigen structure-based antibody profiling also known as modification-assisted profiling (MAP)
  • MAP modification-assisted profiling
  • the antibodies in each bin bind to the same epitope, which can be a unique epitope that is distinct from or partially overlaps with the epitope represented by another bin.
  • ком ⁇ онент that bind to the same epitope refers to antibodies that block the binding of the reference anti-RSV antibody to its antigen by 50% or more in a competitive assay, and conversely, the reference antibody blocks the binding of the antibody to its antigen by 50% or more in a competitive assay.
  • the reference antibody is allowed to bind to RSV under saturation conditions.
  • the ability of the anti-RSV antibody in question to bind to RSV is assessed. If the anti-RSV antibody is able to bind to RSV after the saturation binding of the reference anti-RSV antibody, it can be concluded that the anti-RSV antibody in question binds to different epitopes with the reference anti-RSV antibody. However, if the anti-RSV antibody in question is unable to bind to RSV after the saturation binding of the reference anti-RSV antibody, the anti-RSV antibody in question can bind to the same epitope as the epitope bound by the reference anti-RSV antibody.
  • two antibodies are considered to bind to the same or overlapping expression if a 1, 5, 10, 20 or 100-fold excess of one antibody inhibits the binding of the other by at least 50%, at least 75%, at least 90% or even 99% or more as measured in a competitive binding assay (see, e.g., Junghans et al., Cancer Res. 50 (1990) 1495-1502). Bit.
  • two antibodies are considered to bind to the same epitope if substantially all amino acid mutations in the antigen that reduce or eliminate binding of one antibody also reduce or eliminate binding of the other.
  • Two antibodies are considered to have "overlapping epitopes" if only a subset of amino acid mutations that reduce or eliminate binding of one antibody reduce or eliminate binding of the other.
  • chimeric antibody refers to an antibody in which a portion of the heavy and/or light chain is derived from a particular source or species, while the remainder of the heavy and/or light chain is derived from a different source or species.
  • the "class" of an antibody refers to the type of constant domain or constant region possessed by its heavy chain.
  • the antibody is of the IgG4 isotype, with an S228P mutation in the hinge region to improve the stability of the IgG4 antibody.
  • the heavy chain constant domains corresponding to the different classes of immunoglobulins are called ⁇ , ⁇ , ⁇ , ⁇ , and ⁇ , respectively.
  • cytotoxic agent refers to a substance that inhibits or prevents cell function and/or causes cell death or destruction.
  • Cytotoxic agents include, but are not limited to, radioactive isotopes (e.g., At 211 , I 131 , I 125 , Y 90 , Re 186 , Re 188 , Sm 153 , Bi 212 , p 32 , Pb 212 and radioactive isotopes of Lu); chemotherapeutic agents or drugs (e.g., methotrexate, adriamicin, vinca alkaloids); alkaloids) (vincristine, vinblastine, etoposide, doxorubicin, melphalan, mitomycin C, chlorambucil, daunorubicin or other intercalating agents); growth inhibitors; enzymes and fragments thereof, such as nucleolytic enzymes; antibiotics; toxins, such as small molecule toxins or enzymatically active toxins of
  • Antibody effector functions refer to those biological activities attributable to the Fc region of an antibody and vary with the antibody isotype. Examples of antibody effector functions include: Clq binding and complement dependent cytotoxicity (CDC); Fc receptor binding; antibody-dependent cell-mediated cytotoxicity (ADCC); phagocytosis; downregulation of cell surface receptors (e.g., B cell receptors); and B cell activation.
  • an “effective amount” of an agent refers to an amount effective, at dosages and for periods of time necessary, to achieve the desired therapeutic or prophylactic result.
  • Fc region herein is used to define the C-terminal region of an immunoglobulin heavy chain that contains at least a portion of the constant region.
  • the term includes native sequence Fc regions and variant Fc regions.
  • the human IgG heavy chain Fc region extends from Cys226, or from Pro230 to the carboxyl terminus of the heavy chain.
  • the C-terminal lysine (Lys447) of the Fc region may or may not be present.
  • the anti-RSV antibody as described herein is of the IgG1 isotype and comprises a constant heavy chain domain of SEQ ID NO: 201. In one embodiment, it further comprises a C-terminal lysine (Lys447).
  • the anti-RSV antibody as described herein is of the IgG4 isotype. In one embodiment, it further comprises a C-terminal lysine (Lys447).
  • the numbering of amino acid residues in the Fc region or constant region is according to the EU numbering system, also known as the EU index, as described in Kabat et al., Sequences of Proteins of Immunological Interest, 5th ed. Public Health Service, National Institutes of Health, Bethesda, MD, 1991.
  • FR Framework or "FR” refers to variable domain residues excluding hypervariable region (HVR) residues.
  • HVR hypervariable region
  • the FR of a variable domain consists of four FR domains: FR1, FR2, FR3, and FR4.
  • HVR and FR sequences generally appear in the following order in VH (or VL): FR1-H1 (L1)-FR2-H2 (L2)-FR3-H3 (L3)-FR4.
  • full length antibody “intact antibody,” and “whole antibody” are used interchangeably herein to refer to an antibody that has a structure substantially similar to a native antibody structure or has heavy chains that contain an Fc region as defined herein.
  • host cell refers to cells into which exogenous nucleic acid has been introduced, including the progeny of such cells.
  • Host cells include “transformants” and “transformed cells”, which include the primary transformed cells and the progeny derived therefrom without considering the number of passages.
  • the progeny may not be completely identical to the parent cell in nucleic acid content, but may contain mutations. Mutant progeny having the same function or biological activity as screened or selected in the initial transformed cell are included herein.
  • Human antibody refers to an antibody having an amino acid sequence corresponding to the amino acid sequence of an antibody produced by a human or human cell or derived from a non-human source using a human antibody repertoire or other human antibody coding sequence. This definition of human antibody specifically excludes humanized antibodies comprising non-human antigen binding residues.
  • human antibodies are derived from non-human transgenic mammals, such as mice, rats, or rabbits.
  • human antibodies are derived from hybridoma cell lines.
  • Human consensus framework refers to a framework that represents the most commonly occurring amino acid residues in a selection of human immunoglobulin VL or VH framework sequences.
  • the selection of human immunoglobulin VL or VH sequences is from a subgroup of variable domain sequences.
  • the sequence subgroup is a subgroup such as Kabat et al., Sequences of Proteins of Immunological Interest, 5th Edition, NIH Publication 91-3242, Bethesda MD (1991), Volumes 1-3.
  • the subgroup is subgroup ⁇ I such as Kabat et al., see above.
  • the subgroup III such as Kabat et al., see above.
  • Humanized antibodies refer to chimeric antibodies comprising amino acid residues from non-human HVRs and amino acid residues from human FRs.
  • a humanized antibody will comprise at least one, typically two substantially entire variable domains, wherein all or substantially all HVRs (e.g., CDRs) correspond to those of non-human antibodies, and all or substantially all FRs correspond to those of human antibodies.
  • a humanized antibody may comprise at least a portion of an antibody constant region derived from a human antibody.
  • a "humanized form" of an antibody (e.g., a non-human antibody) refers to an antibody that has undergone humanization.
  • hypervariable region refers to each region of an antibody variable domain that is hypervariable in sequence ("complementarity determining region” or “CDR") and/or forms structurally defined loops ("hypervariable loops") and/or contains antigen contact residues ("antigen contacts”).
  • CDR complementarity determining region
  • hypervariable loops forms structurally defined loops
  • antigen contacts antigen contacts
  • antibodies comprise six HVRs: three in VH (H1, H2, H3) and three in VL (L1, L2, L3).
  • Exemplary HVRs herein include:
  • (d) a combination of (a), (b), and/or (c), comprising HVR amino acid residues 46-56 (L2), 47-56 (L2), 48-56 (L2), 49-56 (L2), 26-35 (H1), 26-35b (H1), 49-65 (H2), 93-102 (H3), and 94-102 (H3).
  • the HVR residues comprise those identified in the description of the amino acid sequences below.
  • HVR residues and other residues in the variable domain are numbered herein according to Kabat et al., supra.
  • immunoconjugate refers to an antibody conjugated to one or more heterologous molecules, including but not limited to a cytotoxic agent.
  • “Individual” or “subject” refers to a mammal. Mammals include, but are not limited to, domesticated animals (e.g., cattle, sheep, cats, dogs, and horses), primates (e.g., humans and non-human primates such as monkeys), rabbits, and rodents (e.g., mice and rats). In certain embodiments, the individual or subject is a human.
  • an “isolated” antibody is one that has been separated from components of its natural environment.
  • the antibody is purified to greater than 95% or 99% purity as determined by, for example, electrophoresis (e.g., SDS-PAGE, isoelectric focusing (IEF), capillary electrophoresis) or chromatography (e.g., ion exchange or reverse phase HPLC methods).
  • electrophoresis e.g., SDS-PAGE, isoelectric focusing (IEF), capillary electrophoresis
  • chromatography e.g., ion exchange or reverse phase HPLC methods.
  • nucleic acid refers to a nucleic acid molecule that has been separated from a component of its natural environment.
  • An isolated nucleic acid includes a nucleic acid molecule contained in cells that ordinarily contain the nucleic acid molecule, but the nucleic acid molecule is present extrachromosomally or at a chromosomal location that is different from its natural chromosomal location.
  • isolated nucleic acid encoding an anti-RSV antibody refers to one or more nucleic acid molecules encoding antibody heavy and light chains (or fragments thereof), including such nucleic acid molecules in a single vector or different vectors, and such nucleic acid molecules present in one or more locations in a host cell.
  • the term "monoclonal antibody” refers to an antibody obtained from a group of substantially homogeneous antibodies, i.e., the individual antibodies constituting the group are identical and/or bind to the same epitope, except for possible variant antibodies that contain naturally occurring mutations or occur during the generation of monoclonal antibody preparations, such variants are generally present in very small amounts. Unlike polyclonal antibody preparations that usually contain different antibodies for different determinants (epitopes), each monoclonal antibody of a monoclonal antibody preparation is directed to a single determinant on an antigen.
  • monoclonal indicates that the antibody is obtained from a group of substantially homogeneous antibodies, and should not be interpreted as requiring antibodies to be generated by any particular method.
  • monoclonal antibodies to be used in accordance with the present invention can be generated by a variety of techniques, including but not limited to hybridoma methods, recombinant DNA methods, phage display methods, and methods utilizing transgenic animals containing all or part of human immunoglobulin loci, such methods and other exemplary methods for generating monoclonal antibodies are described herein.
  • naked antibody refers to an antibody that is not conjugated to a heterologous moiety (eg, a cytotoxic moiety) or a radiolabel. Naked antibodies can be present in a pharmaceutical formulation.
  • Natural antibodies refer to naturally occurring immunoglobulin molecules with different structures.
  • natural IgG antibodies are heterotetrameric glycoproteins of about 150,000 daltons, consisting of two identical light chains and two identical heavy chains bonded by disulfide bonds.
  • VH variable heavy domain
  • CH2 heavy chain variable domain
  • CH3 constant domains
  • VL variable region
  • antibody light chains can be classified into one of two types, called kappa ( ⁇ ) and lambda ( ⁇ ).
  • package insert is used to refer to instructions customarily included in commercial packages of therapeutic products, that contain information about the indications, usage, dosage, administration, combination therapy, contraindications and/or warnings concerning the use of such therapeutic products.
  • Percent (%) amino acid sequence identity with respect to a reference polypeptide sequence is defined as the percentage of amino acid residues in a candidate sequence that are identical to the amino acid residues in the reference polypeptide sequence, after aligning the sequences and introducing gaps, if necessary, to achieve maximum percent sequence identity. Alignment for the purpose of determining percent amino acid sequence identity can be performed in a variety of ways within the skill in the art, for example, using publicly available computer software such as BLAST, BLAST-2, Clustal W, Megalign (DNASTAR) software or the FASTA package. One skilled in the art can determine appropriate parameters for aligning sequences, including any algorithm necessary to achieve maximum alignment over the full length of the sequences being compared.
  • % amino acid sequence identity values are generated using the ggsearch program of the FASTA package, version 36.3.8c or later, and the BLOSUM50 comparison matrix.
  • the FASTA package was written by W.R. Pearson and D.J. Lipman (1988) “Improved Tools for Biological Sequence Analysis,” PNAS 85: 2444-2448; W.R. Pearson (1996) “Effective protein sequence comparison” Meth. Enzymol. 266: 227-258; and Pearson et al. (1997) Genomics 46: 24-36 and is publicly available at http://fasta.bioch.virginia.edu/fasta_www2/fasta_down.shtml.
  • the percent amino acid identity is given in the output alignment title.
  • pharmaceutical formulation refers to a preparation that is in such form as to permit the biological activity of the active ingredient contained therein to be effective, and that contains no additional components that are unacceptably toxic to a subject to which the formulation would be administered.
  • “Pharmaceutically acceptable carrier” refers to a component of a pharmaceutical formulation that is different from the active ingredient and is non-toxic to the subject.
  • Pharmaceutically acceptable carriers include, but are not limited to, buffers, excipients, stabilizers, or preservatives.
  • treatment refers to clinical intervention that attempts to alter the natural course of the individual being treated, and can be performed for prevention or during the course of clinical pathology. Desired effects of treatment include, but are not limited to, preventing the occurrence or recurrence of disease, alleviating symptoms, alleviating/reducing any direct or indirect pathological consequences of the disease, preventing metastasis, reducing the rate of disease progression, ameliorating or alleviating the disease state, and regression or improved prognosis.
  • the antibodies of the invention are used to delay the development of a disease or slow the progression of a disease.
  • prevention includes slowing down the onset of a disease, reducing the risk of developing a disease, inhibiting or delaying manifestation or development of disease-related symptoms, reducing the severity of subsequent contractions or progression of the disease, ameliorating associated symptoms, and inducing immunity to prevent disease,
  • variable region refers to the domain of an antibody heavy or light chain that is involved in the antibody binding to an antigen.
  • the heavy and light chain variable domains (VH and VL, respectively) of natural antibodies generally have similar structures, wherein each domain comprises four conserved framework regions (FRs) and three hypervariable regions (HVRs) (see, e.g., Kindt et al., Kuby Immunology, 6th edition, W.H. Freeman and Co., p. 91 (2007)).
  • FRs conserved framework regions
  • HVRs hypervariable regions
  • VH or VL domains from antibodies that bind to an antigen can be used to screen libraries of complementary VL or VH domains, respectively, to isolate antibodies that bind to a specific antigen. See, e.g., Portolano et al., J. Immunol. 150: 880-887 (1993); Clarkson et al., Nature 352: 624-628 (1991).
  • vector refers to a nucleic acid molecule capable of propagating another nucleic acid to which it is linked.
  • the term includes vectors that are self-replicating nucleic acid structures and vectors that are incorporated into the genome of a host cell into which they are introduced. Certain vectors are capable of directing the expression of nucleic acids to which they are operably linked. Such vectors are referred to herein as "expression vectors.”
  • the invention provides isolated antibodies that bind RSV.
  • antibodies that bind RSV are provided.
  • the antibodies of the invention are useful, for example, for diagnosing or treating RSV infection, such as a lower respiratory tract infection.
  • an anti-RSV antibody is provided, wherein the antibody:
  • RSV pre-F protein more particularly RSV A2 pre-F protein
  • RSV particularly RSV A1, RSV B9320 and/or RSV B18537
  • infecting host cells such as Hep2 cells.
  • the present invention provides an anti-RSV antibody comprising at least one, two, three, four, five, or six CDRs selected from the following: (a) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 1; (b) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 2; (c) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 3; (d) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 4; (e) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 5; and (f) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 6.
  • the present invention provides an antibody comprising at least one, at least two, or all three VH CDR sequences selected from the following: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 1; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 2; and (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 3.
  • the antibody comprises a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 3.
  • the antibody comprises a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 3 and a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 6.
  • the antibody comprises a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 3, a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 6, and a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 2.
  • the antibody comprises (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 1; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 2; and (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 3.
  • the present invention provides an antibody comprising at least one, at least two, or all three VL CDR sequences selected from the following: (a) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 4; (b) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 5; and (c) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 6.
  • the antibody comprises (a) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 4; (b) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 5; and (c) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 6.
  • an antibody of the invention comprises (a) a VH domain comprising at least one, at least two, or all three VH CDR sequences selected from the group consisting of: (i) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 1, (ii) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 2, and (iii) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 3; and (b) a VL domain comprising at least one, at least two, or all three VL CDR sequences selected from the group consisting of: (i) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 1, (ii) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 2, and (iii) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 3. NO:4, (ii) CDR-L2 comprising the amino acid sequence of SEQ ID NO:5, and (ii)
  • the present invention provides an antibody comprising (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 1; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 2; (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 3; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 4; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 5; and (f) a CDR-L3 comprising an amino acid sequence selected from SEQ ID NO: 6.
  • the anti-RSV antibody is human or humanized.
  • the anti-RSV antibody comprises the CDRs as in any of the above embodiments, and further comprises an acceptor human framework, such as a human immunoglobulin framework or a human consensus framework.
  • an anti-RSV antibody comprises a heavy chain variable domain (VH) sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 7.
  • VH sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity contains substitutions (e.g., conservative substitutions), insertions, or deletions relative to the reference sequence, but the anti-RSV antibody comprising the sequence retains the ability to bind RSV.
  • a total of 1 to 10 amino acids are substituted, inserted, and/or deleted in SEQ ID NO: 7.
  • the substitutions, insertions, or deletions occur in regions outside of the CDRs (i.e., in the FRs).
  • the anti-RSV antibody comprises the VH sequence in SEQ ID NO: 7, including post-translational modifications of the sequence.
  • the VH comprises one, two or three CDRs selected from: (a) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 1, (b) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 2, and (c) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 3.
  • an anti-RSV antibody comprising a light chain variable domain (VL) having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 8.
  • VL sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity contains substitutions (e.g., conservative substitutions), insertions, or deletions relative to the reference sequence, but the anti-RSV antibody comprising the sequence retains the ability to bind RSV.
  • the anti-RSV antibody comprises the VL sequence in SEQ ID NO: 8, including post-translational modifications of the sequence.
  • the VL comprises one, two or three CDRs selected from: (a) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 4; (b) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 5; and (c) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 6.
  • an anti-RSV antibody comprising a VH as in any of the embodiments provided above, and a VL as in any of the embodiments provided above.
  • the antibody comprises the VH and VL sequences in SEQ ID NO: 7 and SEQ ID NO: 8, respectively, including post-translational modifications of those sequences.
  • the present invention provides antibodies that bind to the same epitope as the anti-RSV antibodies provided herein.
  • antibodies that bind to the same epitope as the anti-RSV antibodies comprising the VH sequence of SEQ ID NO: 7 and the VL sequence of SEQ ID NO: 8 are provided.
  • the present invention provides an anti-RSV antibody comprising at least one, two, three, four, five, or six CDRs selected from the following: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 9; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 10; (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 11; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 12; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 13; and (f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 14.
  • the present invention provides an antibody comprising at least one, at least two, or all three VH CDR sequences selected from the group consisting of: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 9; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 10; and (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 11.
  • the antibody comprises a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 11.
  • the antibody comprises a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 11 and a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 14.
  • the antibody comprises a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 11, a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 14, and a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 10.
  • the antibody comprises (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 9; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 10; and (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 11.
  • the present invention provides an antibody comprising at least one, at least two, or all three VL CDR sequences selected from the following: (a) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 12; (b) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 13; and (c) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 14.
  • the antibody comprises (a) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 12; (b) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 13; and (c) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 14.
  • the antibody of the present invention comprises (a) a VH domain comprising at least one, at least two, or all three VH CDR sequences selected from the following: (i) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 9, (ii) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 10, and (iii) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 11; and (b) a VL domain comprising at least one, at least two, or all three VL CDR sequences selected from the following: (i) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 12, (ii) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 13, and (c) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 14.
  • the present invention provides an antibody comprising (a) a CDR-H1 comprising an amino acid sequence of SEQ ID NO: 9; (b) a CDR-H2 comprising an amino acid sequence of SEQ ID NO: 10; (c) a CDR-H3 comprising an amino acid sequence of SEQ ID NO: 11; (d) a CDR-L1 comprising an amino acid sequence of SEQ ID NO: 12; (e) a CDR-L2 comprising an amino acid sequence of SEQ ID NO: 13; and (f) a CDR-L3 comprising an amino acid sequence selected from SEQ ID NO: 14.
  • the anti-RSV antibody is human or humanized.
  • the anti-RSV antibody comprises the CDRs as in any of the above embodiments, and further comprises an acceptor human framework, such as a human immunoglobulin framework or a human consensus framework.
  • an anti-RSV antibody comprises a heavy chain variable domain (VH) sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 15.
  • VH sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity contains substitutions (e.g., conservative substitutions), insertions, or deletions relative to the reference sequence, but the anti-RSV antibody comprising the sequence retains the ability to bind RSV.
  • a total of 1 to 10 amino acids are substituted, inserted, and/or deleted in SEQ ID NO: 15.
  • the substitutions, insertions, or deletions occur in regions outside of the CDRs (i.e., in the FRs).
  • the anti-RSV antibody comprises the VH sequence in SEQ ID NO: 15, including post-translational modifications of the sequence.
  • the VH comprises one, two or three CDRs selected from: (a) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 9, (b) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 10, and (c) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 11.
  • an anti-RSV antibody comprising a light chain variable domain (VL) having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 16.
  • VL sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity contains substitutions (e.g., conservative substitutions), insertions, or deletions relative to the reference sequence, but the anti-RSV antibody comprising the sequence retains the ability to bind RSV.
  • the anti-RSV antibody comprises the VL sequence in SEQ ID NO: 16, including post-translational modifications of the sequence.
  • the VL comprises one, two or three CDRs selected from: (a) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 12; (b) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 13; and (c) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 14.
  • an anti-RSV antibody comprising a VH as in any of the embodiments provided above, and a VL as in any of the embodiments provided above.
  • the antibody comprises The VH and VL sequences in SEQ ID NO: 15 and SEQ ID NO: 16, including post-translational modifications of those sequences.
  • the present invention provides antibodies that bind to the same epitope as the anti-RSV antibodies provided herein.
  • antibodies that bind to the same epitope as an anti-RSV antibody comprising a VH sequence of SEQ ID NO: 15 and a VL sequence of SEQ ID NO: 16 are provided.
  • the present invention provides an anti-RSV antibody comprising at least one, two, three, four, five, or six CDRs selected from the following: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 17; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 18; (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 19; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 20; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 21; and (f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 22.
  • the present invention provides an antibody comprising at least one, at least two, or all three VH CDR sequences selected from the following: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 17; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 18; and (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 19.
  • the antibody comprises a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 19.
  • the antibody comprises a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 19 and a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 22.
  • the antibody comprises a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 19, a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 22, and a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 18.
  • the antibody comprises (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 17; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 18; and (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 19.
  • the present invention provides an antibody comprising at least one, at least two, or all three VL CDR sequences selected from the following: (a) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 20; (b) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 21; and (c) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 22.
  • the antibody comprises (a) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 20; (b) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 21; and (c) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 22.
  • the antibody of the present invention comprises (a) a VH domain comprising at least one, at least two, or all three VH CDR sequences selected from the following: (i) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 17, (ii) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 18, and (iii) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 19; and (b) a VL domain comprising at least one, at least two, or all three VL CDR sequences selected from the following: (i) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 20, (ii) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 21, and (c) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 22.
  • the present invention provides an antibody comprising (a) a CDR-H1 comprising an amino acid sequence of SEQ ID NO: 17; (b) a CDR-H2 comprising an amino acid sequence of SEQ ID NO: 18; (c) a CDR-H3 comprising an amino acid sequence of SEQ ID NO: 19; (d) a CDR-L1 comprising an amino acid sequence of SEQ ID NO: 20; (e) a CDR-L2 comprising an amino acid sequence of SEQ ID NO: 21; and (f) a CDR-L3 comprising an amino acid sequence selected from SEQ ID NO: 22.
  • the anti-RSV antibody is human or humanized.
  • the anti-RSV antibody comprises the CDRs as in any of the above embodiments, and further comprises an acceptor human framework, such as a human immunoglobulin framework or a human consensus framework.
  • the anti-RSV antibody comprises a heavy chain variable domain (VH) sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 23.
  • VH sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity contains substitutions (e.g., conservative substitutions), insertions, or deletions relative to the reference sequence, but the anti-RSV antibody comprising the sequence retains the ability to bind RSV.
  • a total of 1 to 10 amino acids are substituted, inserted and/or deleted in SEQ ID NO: 23.
  • the substitutions, insertions, or deletions occur in regions outside of the CDRs (i.e., in the FRs).
  • the anti-RSV antibody comprises the VH sequence in SEQ ID NO: 23, including post-translational modifications of the sequence.
  • the VH comprises one, two or three selected from the following CDR: (a) CDR-H1 comprising the amino acid sequence of SEQ ID NO:17, (b) CDR-H2 comprising the amino acid sequence of SEQ ID NO:18, and (c) CDR-H3 comprising the amino acid sequence of SEQ ID NO:19.
  • an anti-RSV antibody comprising a light chain variable domain (VL) having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 24.
  • VL sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity contains substitutions (e.g., conservative substitutions), insertions, or deletions relative to the reference sequence, but the anti-RSV antibody comprising the sequence retains the ability to bind to RSV.
  • the anti-RSV antibody comprises the VL sequence in SEQ ID NO: 24, including post-translational modifications of the sequence.
  • the VL comprises one, two or three CDRs selected from: (a) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 20; (b) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 21; and (c) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 22.
  • an anti-RSV antibody comprising a VH as in any of the embodiments provided above, and a VL as in any of the embodiments provided above.
  • the antibody comprises the VH and VL sequences in SEQ ID NO: 23 and SEQ ID NO: 24, respectively, including post-translational modifications of those sequences.
  • the present invention provides antibodies that bind to the same epitope as the anti-RSV antibodies provided herein.
  • antibodies that bind to the same epitope as an anti-RSV antibody comprising a VH sequence of SEQ ID NO: 23 and a VL sequence of SEQ ID NO: 24 are provided.
  • the present invention provides an anti-RSV antibody comprising at least one, two, three, four, five, or six CDRs selected from the following: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 25; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 26; (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 27; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 28; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 29; and (f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 30.
  • the present invention provides an antibody comprising at least one, at least two, or all three VH CDR sequences selected from the following: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 25; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 26; and (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 27.
  • the antibody comprises a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 27.
  • the antibody comprises a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 27 and a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 30.
  • the antibody comprises a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 27, a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 30, and a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 26.
  • the antibody comprises (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 25; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 26; and (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 27.
  • the present invention provides an antibody comprising at least one, at least two, or all three VL CDR sequences selected from the following: (a) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 28; (b) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 29; and (c) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 30.
  • the antibody comprises (a) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 28; (b) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 29; and (c) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 30.
  • the antibody of the present invention comprises (a) a VH domain comprising at least one, at least two, or all three VH CDR sequences selected from the following: (i) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 25, (ii) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 26, and (iii) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 27; and (b) a VL domain comprising at least one, at least two, or all three VL CDR sequences selected from the following: (i) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 28, (ii) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 29, and (c) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 30.
  • the present invention provides an antibody comprising (a) an amino acid sequence comprising SEQ ID NO: 25; CDR-H1; (b) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 26; (c) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 27; (d) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 28; (e) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 29; and (f) CDR-L3 comprising an amino acid sequence selected from SEQ ID NO: 30.
  • the anti-RSV antibody is human or humanized.
  • the anti-RSV antibody comprises the CDRs as in any of the above embodiments, and further comprises an acceptor human framework, such as a human immunoglobulin framework or a human consensus framework.
  • an anti-RSV antibody comprises a heavy chain variable domain (VH) sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 31.
  • VH sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity contains substitutions (e.g., conservative substitutions), insertions, or deletions relative to the reference sequence, but the anti-RSV antibody comprising the sequence retains the ability to bind RSV.
  • the anti-RSV antibody comprises the VH sequence in SEQ ID NO: 31, including post-translational modifications of the sequence.
  • the VH comprises one, two or three CDRs selected from: (a) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 25, (b) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 26, and (c) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 27.
  • an anti-RSV antibody comprising a light chain variable domain (VL) having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 32.
  • VL sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity contains substitutions (e.g., conservative substitutions), insertions, or deletions relative to the reference sequence, but the anti-RSV antibody comprising the sequence retains the ability to bind RSV.
  • the anti-RSV antibody comprises the VL sequence in SEQ ID NO: 32, including post-translational modifications of the sequence.
  • the VL comprises one, two or three CDRs selected from: (a) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 28; (b) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 29; and (c) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 30.
  • an anti-RSV antibody comprising a VH as in any of the embodiments provided above, and a VL as in any of the embodiments provided above.
  • the antibody comprises the VH and VL sequences in SEQ ID NO: 31 and SEQ ID NO: 32, respectively, including post-translational modifications of those sequences.
  • the present invention provides antibodies that bind to the same epitope as the anti-RSV antibodies provided herein.
  • antibodies that bind to the same epitope as an anti-RSV antibody comprising a VH sequence of SEQ ID NO: 31 and a VL sequence of SEQ ID NO: 32 are provided.
  • the present invention provides an anti-RSV antibody comprising at least one, two, three, four, five, or six CDRs selected from the following: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 33; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 34; (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 35; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 36; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 37; and (f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 38.
  • the present invention provides an antibody comprising at least one, at least two, or all three VH CDR sequences selected from the group consisting of: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 33; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 34; and (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 35.
  • the antibody comprises a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 35.
  • the antibody comprises a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 35 and a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 38.
  • the antibody comprises a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 35, a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 38, and a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 34.
  • the antibody comprises (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 33; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 34; and (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 35.
  • the present invention provides an antibody comprising at least one, at least two, or all three VL CDR sequences selected from the following: (a) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 36; (b) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 37; and (c) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 38.
  • the antibody comprises (a) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 36; (b) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 37; and (c) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 38.
  • the antibody of the present invention comprises (a) a VH domain comprising at least one, at least two, or all three VH CDR sequences selected from the following: (i) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 33, (ii) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 34, and (iii) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 35; and (b) a VL domain comprising at least one, at least two, or all three VL CDR sequences selected from the following: (i) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 36, (ii) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 37, and (c) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 38.
  • the present invention provides an antibody comprising (a) a CDR-H1 comprising an amino acid sequence of SEQ ID NO: 33; (b) a CDR-H2 comprising an amino acid sequence of SEQ ID NO: 34; (c) a CDR-H3 comprising an amino acid sequence of SEQ ID NO: 35; (d) a CDR-L1 comprising an amino acid sequence of SEQ ID NO: 36; (e) a CDR-L2 comprising an amino acid sequence of SEQ ID NO: 37; and (f) a CDR-L3 comprising an amino acid sequence selected from SEQ ID NO: 38.
  • the anti-RSV antibody is human or humanized.
  • the anti-RSV antibody comprises the CDRs as in any of the above embodiments, and further comprises an acceptor human framework, such as a human immunoglobulin framework or a human consensus framework.
  • an anti-RSV antibody comprises a heavy chain variable domain (VH) sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 39.
  • VH sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity contains substitutions (e.g., conservative substitutions), insertions, or deletions relative to the reference sequence, but the anti-RSV antibody comprising the sequence retains the ability to bind RSV.
  • the anti-RSV antibody comprises the VH sequence in SEQ ID NO: 39, including post-translational modifications of the sequence.
  • the VH comprises one, two or three CDRs selected from: (a) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 33, (b) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 34, and (c) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 35.
  • an anti-RSV antibody comprising a light chain variable domain (VL) having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 40.
  • VL sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity contains substitutions (e.g., conservative substitutions), insertions, or deletions relative to the reference sequence, but the anti-RSV antibody comprising the sequence retains the ability to bind RSV.
  • the anti-RSV antibody comprises the VL sequence in SEQ ID NO: 40, including post-translational modifications of the sequence.
  • the VL comprises one, two or three CDRs selected from: (a) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 36; (b) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 37; and (c) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 38.
  • an anti-RSV antibody comprising a VH as in any of the embodiments provided above, and a VL as in any of the embodiments provided above.
  • the antibody comprises the VH and VL sequences in SEQ ID NO: 39 and SEQ ID NO: 40, respectively, including post-translational modifications of those sequences.
  • the invention provides antibodies that bind to the same epitope as the anti-RSV antibodies provided herein.
  • an antibody that binds to the same epitope as the anti-RSV antibodies provided herein is provided.
  • Anti-RSV antibodies that bind to the same epitope is provided.
  • the present invention provides an anti-RSV antibody comprising at least one, two, three, four, five, or six CDRs selected from the following: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 41; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 42; (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 43; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 44; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 45; and (f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 46.
  • the present invention provides an antibody comprising at least one, at least two, or all three VH CDR sequences selected from the following: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 41; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 42; and (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 43.
  • the antibody comprises a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 43.
  • the antibody comprises a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 43 and a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 46.
  • the antibody comprises a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 43, a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 46, and a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 42.
  • the antibody comprises (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 41; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 42; and (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 43.
  • the present invention provides an antibody comprising at least one, at least two, or all three VL CDR sequences selected from the following: (a) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 44; (b) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 45; and (c) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 46.
  • the antibody comprises (a) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 44; (b) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 45; and (c) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 46.
  • the antibody of the present invention comprises (a) a VH domain comprising at least one, at least two, or all three VH CDR sequences selected from the following: (i) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 41, (ii) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 42, and (iii) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 43; and (b) a VL domain comprising at least one, at least two, or all three VL CDR sequences selected from the following: (i) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 44, (ii) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 45, and (c) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 46.
  • the present invention provides an antibody comprising (a) a CDR-H1 comprising an amino acid sequence of SEQ ID NO: 41; (b) a CDR-H2 comprising an amino acid sequence of SEQ ID NO: 42; (c) a CDR-H3 comprising an amino acid sequence of SEQ ID NO: 43; (d) a CDR-L1 comprising an amino acid sequence of SEQ ID NO: 44; (e) a CDR-L2 comprising an amino acid sequence of SEQ ID NO: 45; and (f) a CDR-L3 comprising an amino acid sequence selected from SEQ ID NO: 46.
  • the anti-RSV antibody is human or humanized.
  • the anti-RSV antibody comprises the CDRs as in any of the above embodiments, and further comprises an acceptor human framework, such as a human immunoglobulin framework or a human consensus framework.
  • an anti-RSV antibody comprises a heavy chain variable domain (VH) sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 47.
  • VH sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity contains substitutions (e.g., conservative substitutions), insertions, or deletions relative to the reference sequence, but the anti-RSV antibody comprising the sequence retains the ability to bind RSV.
  • the anti-RSV antibody comprises the VH sequence in SEQ ID NO: 47, including post-translational modifications of the sequence.
  • the VH comprises one, two or three CDRs selected from: (a) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 41, (b) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 42, and (c) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 43.
  • an anti-RSV antibody comprising the amino acid sequence of SEQ ID NO: 48.
  • the sequence has a light chain variable domain (VL) with at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity.
  • VL light chain variable domain
  • the VL sequence with at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity contains substitutions (e.g., conservative substitutions), insertions, or deletions relative to the reference sequence, but the anti-RSV antibody comprising the sequence retains the ability to bind RSV.
  • a total of 1 to 10 amino acids are substituted, inserted, and/or deleted in SEQ ID NO: 48.
  • the substitution, insertion, or deletion occurs in a region other than a CDR (i.e., in a FR).
  • the anti-RSV antibody comprises the VL sequence in SEQ ID NO: 48, including post-translational modifications of the sequence.
  • the VL comprises one, two or three CDRs selected from: (a) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 44; (b) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 45; and (c) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 46.
  • an anti-RSV antibody comprising a VH as in any of the embodiments provided above, and a VL as in any of the embodiments provided above.
  • the antibody comprises the VH and VL sequences in SEQ ID NO: 47 and SEQ ID NO: 48, respectively, including post-translational modifications of those sequences.
  • the present invention provides antibodies that bind to the same epitope as the anti-RSV antibodies provided herein.
  • antibodies that bind to the same epitope as an anti-RSV antibody comprising a VH sequence of SEQ ID NO: 47 and a VL sequence of SEQ ID NO: 48 are provided.
  • the present invention provides an anti-RSV antibody comprising at least one, two, three, four, five, or six CDRs selected from the following: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 49; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 50; (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 51; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 52; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 53; and (f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 54.
  • the present invention provides an antibody comprising at least one, at least two, or all three VH CDR sequences selected from the following: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 49; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 50; and (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 51.
  • the antibody comprises a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 51.
  • the antibody comprises a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 51 and a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 54.
  • the antibody comprises a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 51, a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 54, and a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 50.
  • the antibody comprises (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 49; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 50; and (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 51.
  • the present invention provides an antibody comprising at least one, at least two, or all three VL CDR sequences selected from the following: (a) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 52; (b) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 53; and (c) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 54.
  • the antibody comprises (a) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 52; (b) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 53; and (c) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 54.
  • the antibody of the present invention comprises (a) a VH domain comprising at least one, at least two, or all three VH CDR sequences selected from the following: (i) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 49, (ii) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 50, and (iii) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 51; and (b) a VL domain comprising at least one, at least two, or all three VL CDR sequences selected from the following: (i) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 52, (ii) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 53, and (c) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 54.
  • the present invention provides an antibody comprising (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 49; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 50; (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 51; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 52; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 53; and (f) a CDR-L3 comprising an amino acid sequence selected from SEQ ID NO: 54.
  • the anti-RSV antibody is human or humanized.
  • the anti-RSV antibody comprises the CDRs as in any of the above embodiments, and further comprises an acceptor human framework, such as a human immunoglobulin framework or a human consensus framework.
  • an anti-RSV antibody comprises a heavy chain variable domain (VH) sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 55.
  • VH sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity contains substitutions (e.g., conservative substitutions), insertions, or deletions relative to the reference sequence, but the anti-RSV antibody comprising the sequence retains the ability to bind RSV.
  • the anti-RSV antibody comprises the VH sequence in SEQ ID NO: 55, including post-translational modifications of the sequence.
  • the VH comprises one, two or three CDRs selected from: (a) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 49, (b) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 50, and (c) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 51.
  • an anti-RSV antibody comprising a light chain variable domain (VL) having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 56.
  • VL sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity contains substitutions (e.g., conservative substitutions), insertions, or deletions relative to the reference sequence, but the anti-RSV antibody comprising the sequence retains the ability to bind to RSV.
  • the anti-RSV antibody comprises the VL sequence in SEQ ID NO: 56, including post-translational modifications of the sequence.
  • the VL comprises one, two or three CDRs selected from: (a) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 52; (b) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 53; and (c) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 54.
  • an anti-RSV antibody comprising a VH as in any of the embodiments provided above, and a VL as in any of the embodiments provided above.
  • the antibody comprises the VH and VL sequences in SEQ ID NO: 55 and SEQ ID NO: 56, respectively, including post-translational modifications of those sequences.
  • the present invention provides antibodies that bind to the same epitope as the anti-RSV antibodies provided herein.
  • antibodies that bind to the same epitope as an anti-RSV antibody comprising a VH sequence of SEQ ID NO: 55 and a VL sequence of SEQ ID NO: 56 are provided.
  • the present invention provides an anti-RSV antibody comprising at least one, two, three, four, five, or six CDRs selected from the following: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 57; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 58; (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 59; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 60; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 61; and (f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 62.
  • the present invention provides an antibody comprising at least one, at least two, or all three VH CDR sequences selected from the following: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 57; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 58; and (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 59.
  • the antibody comprises a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 59.
  • the antibody comprises a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 59 and a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 62.
  • the antibody comprises a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 59, a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 62, and a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 58.
  • the antibody comprises (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 57; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 58; and (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 59.
  • the present invention provides an antibody comprising at least one, at least two, or all three selected from The following VL CDR sequences: (a) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 60; (b) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 61; and (c) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 62.
  • the antibody comprises (a) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 60; (b) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 61; and (c) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 62.
  • the antibody of the present invention comprises (a) a VH domain comprising at least one, at least two, or all three VH CDR sequences selected from the following: (i) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 57, (ii) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 58, and (iii) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 59; and (b) a VL domain comprising at least one, at least two, or all three VL CDR sequences selected from the following: (i) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 60, (ii) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 61, and (c) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 62.
  • the present invention provides an antibody comprising (a) a CDR-H1 comprising an amino acid sequence of SEQ ID NO: 57; (b) a CDR-H2 comprising an amino acid sequence of SEQ ID NO: 58; (c) a CDR-H3 comprising an amino acid sequence of SEQ ID NO: 59; (d) a CDR-L1 comprising an amino acid sequence of SEQ ID NO: 60; (e) a CDR-L2 comprising an amino acid sequence of SEQ ID NO: 61; and (f) a CDR-L3 comprising an amino acid sequence selected from SEQ ID NO: 62.
  • the anti-RSV antibody is human or humanized.
  • the anti-RSV antibody comprises the CDRs as in any of the above embodiments, and further comprises an acceptor human framework, such as a human immunoglobulin framework or a human consensus framework.
  • an anti-RSV antibody comprises a heavy chain variable domain (VH) sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 63.
  • VH sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity contains substitutions (e.g., conservative substitutions), insertions, or deletions relative to the reference sequence, but the anti-RSV antibody comprising the sequence retains the ability to bind RSV.
  • the anti-RSV antibody comprises the VH sequence in SEQ ID NO: 63, including post-translational modifications of the sequence.
  • the VH comprises one, two or three CDRs selected from: (a) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 57, (b) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 58, and (c) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 59.
  • an anti-RSV antibody comprising a light chain variable domain (VL) having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 64.
  • VL sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity contains substitutions (e.g., conservative substitutions), insertions, or deletions relative to the reference sequence, but the anti-RSV antibody comprising the sequence retains the ability to bind RSV.
  • the anti-RSV antibody comprises the VL sequence in SEQ ID NO: 64, including post-translational modifications of the sequence.
  • the VL comprises one, two or three CDRs selected from: (a) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 60; (b) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 61; and (c) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 62.
  • an anti-RSV antibody comprising a VH as in any of the embodiments provided above, and a VL as in any of the embodiments provided above.
  • the antibody comprises the VH and VL sequences in SEQ ID NO: 63 and SEQ ID NO: 64, respectively, including post-translational modifications of those sequences.
  • the present invention provides antibodies that bind to the same epitope as the anti-RSV antibodies provided herein.
  • antibodies that bind to the same epitope as an anti-RSV antibody comprising a VH sequence of SEQ ID NO: 63 and a VL sequence of SEQ ID NO: 64 are provided.
  • the present invention provides an anti-RSV antibody comprising at least one, two, three, four, five, or six CDRs selected from the following: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 65; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 66; (c) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 66; (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 67; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 68; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 69; and (f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 70.
  • the present invention provides an antibody comprising at least one, at least two, or all three VH CDR sequences selected from the following: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 65; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 66; and (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 67.
  • the antibody comprises a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 67.
  • the antibody comprises a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 67 and a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 70.
  • the antibody comprises a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 67, a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 70, and a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 66.
  • the antibody comprises (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 65; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 66; and (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 67.
  • the present invention provides an antibody comprising at least one, at least two, or all three VL CDR sequences selected from the following: (a) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 68; (b) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 69; and (c) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 70.
  • the antibody comprises (a) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 68; (b) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 69; and (c) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 70.
  • the antibody of the present invention comprises (a) a VH domain comprising at least one, at least two, or all three VH CDR sequences selected from the following: (i) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 65, (ii) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 66, and (iii) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 67; and (b) a VL domain comprising at least one, at least two, or all three VL CDR sequences selected from the following: (i) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 68, (ii) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 69, and (c) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 70.
  • VH domain comprising at least one, at least two, or all three VH CDR sequences selected from the following: (i) CDR-H1 comprising the
  • the present invention provides an antibody comprising (a) a CDR-H1 comprising an amino acid sequence of SEQ ID NO: 65; (b) a CDR-H2 comprising an amino acid sequence of SEQ ID NO: 66; (c) a CDR-H3 comprising an amino acid sequence of SEQ ID NO: 67; (d) a CDR-L1 comprising an amino acid sequence of SEQ ID NO: 68; (e) a CDR-L2 comprising an amino acid sequence of SEQ ID NO: 69; and (f) a CDR-L3 comprising an amino acid sequence selected from SEQ ID NO: 70.
  • the anti-RSV antibody is human or humanized.
  • the anti-RSV antibody comprises the CDRs as in any of the above embodiments, and further comprises an acceptor human framework, such as a human immunoglobulin framework or a human consensus framework.
  • an anti-RSV antibody comprises a heavy chain variable domain (VH) sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 71.
  • VH sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity contains substitutions (e.g., conservative substitutions), insertions, or deletions relative to the reference sequence, but the anti-RSV antibody comprising the sequence retains the ability to bind RSV.
  • the anti-RSV antibody comprises the VH sequence in SEQ ID NO: 71, including post-translational modifications of the sequence.
  • the VH comprises one, two or three CDRs selected from: (a) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 65, (b) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 66, and (c) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 67.
  • an anti-RSV antibody comprising a light chain variable domain (VL) having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 72.
  • VL sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity contains substitutions (e.g., conservative substitutions), insertions, or deletions relative to the reference sequence.
  • the anti-RSV antibody comprising the sequence retains the ability to bind RSV.
  • the anti-RSV antibody comprises the VL sequence in SEQ ID NO: 72, including post-translational modifications of the sequence.
  • the VL comprises one, two or three CDRs selected from the following: (a) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 68; (b) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 69; and (c) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 70.
  • an anti-RSV antibody comprising a VH as in any of the embodiments provided above, and a VL as in any of the embodiments provided above.
  • the antibody comprises the VH and VL sequences in SEQ ID NO: 71 and SEQ ID NO: 72, respectively, including post-translational modifications of those sequences.
  • the present invention provides antibodies that bind to the same epitope as the anti-RSV antibodies provided herein.
  • antibodies that bind to the same epitope as an anti-RSV antibody comprising a VH sequence of SEQ ID NO: 71 and a VL sequence of SEQ ID NO: 72 are provided.
  • the present invention provides an anti-RSV antibody comprising at least one, two, three, four, five, or six CDRs selected from the following: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 73; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 74; (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 75; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 76; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 77; and (f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 78.
  • the present invention provides an antibody comprising at least one, at least two, or all three VH CDR sequences selected from the following: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 73; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 74; and (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 75.
  • the antibody comprises a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 75.
  • the antibody comprises a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 75 and a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 78.
  • the antibody comprises a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 75, a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 78, and a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 74.
  • the antibody comprises (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 73; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 74; and (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 75.
  • the present invention provides an antibody comprising at least one, at least two, or all three VL CDR sequences selected from the following: (a) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 76; (b) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 77; and (c) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 78.
  • the antibody comprises (a) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 76; (b) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 77; and (c) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 78.
  • the antibody of the present invention comprises (a) a VH domain comprising at least one, at least two, or all three VH CDR sequences selected from the following: (i) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 73, (ii) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 74, and (iii) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 75; and (b) a VL domain comprising at least one, at least two, or all three VL CDR sequences selected from the following: (i) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 76, (ii) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 77, and (c) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 78.
  • the present invention provides an antibody comprising (a) a CDR-H1 comprising an amino acid sequence of SEQ ID NO: 73; (b) a CDR-H2 comprising an amino acid sequence of SEQ ID NO: 74; (c) a CDR-H3 comprising an amino acid sequence of SEQ ID NO: 75; (d) a CDR-L1 comprising an amino acid sequence of SEQ ID NO: 76; (e) a CDR-L2 comprising an amino acid sequence of SEQ ID NO: 77; and (f) a CDR-L3 comprising an amino acid sequence selected from SEQ ID NO: 78.
  • the anti-RSV antibody is human or humanized.
  • the anti-RSV antibody comprises the CDRs as in any of the above embodiments, and further comprises an acceptor human framework, such as a human immunoglobulin framework or a human consensus framework.
  • an anti-RSV antibody comprises a heavy chain variable domain (VH) sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 79.
  • VH sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity contains substitutions (e.g., conservative substitutions), insertions, or deletions relative to the reference sequence, but the anti-RSV antibody comprising the sequence retains the ability to bind RSV.
  • the anti-RSV antibody comprises the VH sequence in SEQ ID NO: 79, including post-translational modifications of the sequence.
  • the VH comprises one, two or three CDRs selected from: (a) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 73, (b) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 74, and (c) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 75.
  • an anti-RSV antibody comprising a light chain variable domain (VL) having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 80.
  • VL sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity contains substitutions (e.g., conservative substitutions), insertions, or deletions relative to the reference sequence, but the anti-RSV antibody comprising the sequence retains the ability to bind RSV.
  • a total of 1 to 10 amino acids are substituted, inserted, and/or deleted in SEQ ID NO: 80.
  • the substitution, insertion, or deletion occurs in a region outside of a CDR (i.e., in a FR).
  • the anti-RSV antibody comprises the VL sequence in SEQ ID NO: 80, including post-translational modifications of the sequence.
  • the VL comprises one, two or three CDRs selected from: (a) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 76; (b) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 77; and (c) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 78.
  • an anti-RSV antibody comprising a VH as in any of the embodiments provided above, and a VL as in any of the embodiments provided above.
  • the antibody comprises the VH and VL sequences in SEQ ID NO: 79 and SEQ ID NO: 80, respectively, including post-translational modifications of those sequences.
  • the present invention provides antibodies that bind to the same epitope as the anti-RSV antibodies provided herein.
  • antibodies that bind to the same epitope as an anti-RSV antibody comprising a VH sequence of SEQ ID NO: 79 and a VL sequence of SEQ ID NO: 80 are provided.
  • the present invention provides an anti-RSV antibody comprising at least one, two, three, four, five, or six CDRs selected from the following: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 81; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 82; (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 83; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 84; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 85; and (f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 86.
  • the present invention provides an antibody comprising at least one, at least two, or all three VH CDR sequences selected from the following: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 81; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 82; and (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 83.
  • the antibody comprises a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 83.
  • the antibody comprises a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 83 and a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 86.
  • the antibody comprises a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 83, a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 86, and a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 82.
  • the antibody comprises (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 81; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 82; and (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 83.
  • the present invention provides an antibody comprising at least one, at least two, or all three VL CDR sequences selected from the group consisting of: (a) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 84; (b) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 85; and (c) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 86.
  • the antibody comprises (a) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 84; (b) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 85; and (c) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 86. and (c) a CDR-L2 comprising the amino acid sequence of SEQ ID NO:85; and (c) a CDR-L3 comprising the amino acid sequence of SEQ ID NO:86.
  • the antibody of the present invention comprises (a) a VH domain comprising at least one, at least two, or all three VH CDR sequences selected from the following: (i) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 81, (ii) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 82, and (iii) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 83; and (b) a VL domain comprising at least one, at least two, or all three VL CDR sequences selected from the following: (i) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 84, (ii) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 85, and (c) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 86.
  • the present invention provides an antibody comprising (a) a CDR-H1 comprising an amino acid sequence of SEQ ID NO: 81; (b) a CDR-H2 comprising an amino acid sequence of SEQ ID NO: 82; (c) a CDR-H3 comprising an amino acid sequence of SEQ ID NO: 83; (d) a CDR-L1 comprising an amino acid sequence of SEQ ID NO: 84; (e) a CDR-L2 comprising an amino acid sequence of SEQ ID NO: 85; and (f) a CDR-L3 comprising an amino acid sequence selected from SEQ ID NO: 86.
  • the anti-RSV antibody is human or humanized.
  • the anti-RSV antibody comprises the CDRs as in any of the above embodiments, and further comprises an acceptor human framework, such as a human immunoglobulin framework or a human consensus framework.
  • an anti-RSV antibody comprises a heavy chain variable domain (VH) sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 87.
  • VH sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity contains substitutions (e.g., conservative substitutions), insertions, or deletions relative to the reference sequence, but the anti-RSV antibody comprising the sequence retains the ability to bind RSV.
  • the anti-RSV antibody comprises the VH sequence in SEQ ID NO: 87, including post-translational modifications of the sequence.
  • the VH comprises one, two or three CDRs selected from: (a) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 81, (b) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 82, and (c) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 83.
  • an anti-RSV antibody comprising a light chain variable domain (VL) having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 88.
  • VL sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity contains substitutions (e.g., conservative substitutions), insertions, or deletions relative to the reference sequence, but the anti-RSV antibody comprising the sequence retains the ability to bind to RSV.
  • a total of 1 to 10 amino acids are substituted, inserted, and/or deleted in SEQ ID NO: 88.
  • the substitution, insertion, or deletion occurs in a region outside of a CDR (i.e., in a FR).
  • the anti-RSV antibody comprises the VL sequence in SEQ ID NO: 88, including post-translational modifications of the sequence.
  • the VL comprises one, two or three CDRs selected from: (a) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 84; (b) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 85; and (c) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 86.
  • an anti-RSV antibody comprising a VH as in any of the embodiments provided above, and a VL as in any of the embodiments provided above.
  • the antibody comprises the VH and VL sequences in SEQ ID NO: 87 and SEQ ID NO: 88, respectively, including post-translational modifications of those sequences.
  • the present invention provides antibodies that bind to the same epitope as the anti-RSV antibodies provided herein.
  • antibodies that bind to the same epitope as an anti-RSV antibody comprising a VH sequence of SEQ ID NO: 87 and a VL sequence of SEQ ID NO: 88 are provided.
  • the present invention provides an anti-RSV antibody comprising at least one, two, three, four, five, or six CDRs selected from the following: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 89; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 90; (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 91; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 92; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 93; and (f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 94.
  • the present invention provides an antibody comprising at least one, at least two, or all three VH CDR sequences selected from the following: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 89; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 90; and (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 91.
  • the antibody comprises a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 91.
  • the antibody comprises a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 91 and a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 94.
  • the antibody comprises a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 91, a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 94, and a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 90.
  • the antibody comprises (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 89; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 90; and (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 91.
  • the present invention provides an antibody comprising at least one, at least two, or all three VL CDR sequences selected from the following: (a) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 92; (b) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 93; and (c) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 94.
  • the antibody comprises (a) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 92; (b) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 93; and (c) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 94.
  • the antibody of the present invention comprises (a) a VH domain comprising at least one, at least two, or all three VH CDR sequences selected from the following: (i) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 89, (ii) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 90, and (iii) CDR-H3 comprising the amino acid sequence selected from SEQ ID NO: 91; and (b) a VL domain comprising at least one, at least two, or all three VL CDR sequences selected from the following: (i) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 92, (ii) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 93, and (c) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 94.
  • the present invention provides an antibody comprising (a) a CDR-H1 comprising an amino acid sequence of SEQ ID NO: 89; (b) a CDR-H2 comprising an amino acid sequence of SEQ ID NO: 90; (c) a CDR-H3 comprising an amino acid sequence of SEQ ID NO: 91; (d) a CDR-L1 comprising an amino acid sequence of SEQ ID NO: 92; (e) a CDR-L2 comprising an amino acid sequence of SEQ ID NO: 93; and (f) a CDR-L3 comprising an amino acid sequence selected from SEQ ID NO: 94.
  • the anti-RSV antibody is human or humanized.
  • the anti-RSV antibody comprises the CDRs as in any of the above embodiments, and further comprises an acceptor human framework, such as a human immunoglobulin framework or a human consensus framework.
  • an anti-RSV antibody comprises a heavy chain variable domain (VH) sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 95.
  • VH sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity contains substitutions (e.g., conservative substitutions), insertions, or deletions relative to the reference sequence, but the anti-RSV antibody comprising the sequence retains the ability to bind RSV.
  • the anti-RSV antibody comprises the VH sequence in SEQ ID NO: 95, including post-translational modifications of the sequence.
  • the VH comprises one, two or three CDRs selected from: (a) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 89, (b) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 90, and (c) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 91.
  • an anti-RSV antibody comprising a light chain variable domain (VL) having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 96.
  • VL sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity contains substitutions (e.g., conservative substitutions), insertions, or deletions relative to the reference sequence, but the anti-RSV antibody comprising the sequence retains the ability to bind to RSV.
  • the anti-RSV antibody comprises the amino acid sequence of SEQ ID NO: 96.
  • the VL comprises one, two or three CDRs selected from the group consisting of: (a) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 92; (b) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 93; and (c) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 94.
  • an anti-RSV antibody comprising a VH as in any of the embodiments provided above, and a VL as in any of the embodiments provided above.
  • the antibody comprises the VH and VL sequences in SEQ ID NO: 95 and SEQ ID NO: 96, respectively, including post-translational modifications of those sequences.
  • the present invention provides antibodies that bind to the same epitope as the anti-RSV antibodies provided herein.
  • antibodies that bind to the same epitope as an anti-RSV antibody comprising a VH sequence of SEQ ID NO: 95 and a VL sequence of SEQ ID NO: 96 are provided.
  • the present invention provides an anti-RSV antibody comprising at least one, two, three, four, five, or six CDRs selected from the following: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 97; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 98; (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 99; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 100; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 101; and (f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 102.
  • the present invention provides an antibody comprising at least one, at least two, or all three VH CDR sequences selected from the following: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 97; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 98; and (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 99.
  • the antibody comprises a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 99.
  • the antibody comprises a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 99 and a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 102.
  • the antibody comprises a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 99, a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 102, and a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 98.
  • the antibody comprises (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 97; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 98; and (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 99.
  • the present invention provides an antibody comprising at least one, at least two, or all three VL CDR sequences selected from the following: (a) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 100; (b) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 101; and (c) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 102.
  • the antibody comprises (a) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 100; (b) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 101; and (c) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 102.
  • the antibody of the present invention comprises (a) a VH domain comprising at least one, at least two, or all three VH CDR sequences selected from the following: (i) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 97, (ii) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 98, and (iii) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 99; and (b) a VL domain comprising at least one, at least two, or all three VL CDR sequences selected from the following: (i) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 100, (ii) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 101, and (c) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 102.
  • the present invention provides an antibody comprising (a) a CDR-H1 comprising an amino acid sequence of SEQ ID NO: 97; (b) a CDR-H2 comprising an amino acid sequence of SEQ ID NO: 98; (c) a CDR-H3 comprising an amino acid sequence of SEQ ID NO: 99; (d) a CDR-L1 comprising an amino acid sequence of SEQ ID NO: 100; (e) a CDR-L2 comprising an amino acid sequence of SEQ ID NO: 101; and (f) a CDR-L3 comprising an amino acid sequence selected from SEQ ID NO: 102.
  • the anti-RSV antibody is human or humanized.
  • the anti-RSV antibody comprises the CDRs as in any of the above embodiments, and further comprises an acceptor human framework, such as a human immunoglobulin framework or a human consensus framework.
  • the anti-RSV antibody comprises a heavy chain variable domain (VH) sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO:103.
  • VH heavy chain variable domain
  • a VH sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity contains substitutions (e.g., conservative substitutions), insertions, or deletions relative to a reference sequence, but an anti-RSV antibody comprising the sequence retains the ability to bind to RSV.
  • the anti-RSV antibody comprises the VH sequence in SEQ ID NO: 103, including post-translational modifications of the sequence.
  • the VH comprises one, two, or three CDRs selected from the following: (a) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 97, (b) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 98, and (c) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 99.
  • an anti-RSV antibody comprising a light chain variable domain (VL) having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 104.
  • VL sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity contains substitutions (e.g., conservative substitutions), insertions, or deletions relative to the reference sequence, but the anti-RSV antibody comprising the sequence retains the ability to bind to RSV.
  • the anti-RSV antibody comprises the VL sequence in SEQ ID NO: 104, including post-translational modifications of the sequence.
  • the VL comprises one, two or three CDRs selected from: (a) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 100; (b) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 101; and (c) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 102.
  • an anti-RSV antibody comprising a VH as in any of the embodiments provided above, and a VL as in any of the embodiments provided above.
  • the antibody comprises the VH and VL sequences in SEQ ID NO: 103 and SEQ ID NO: 104, respectively, including post-translational modifications of those sequences.
  • the present invention provides antibodies that bind to the same epitope as the anti-RSV antibodies provided herein.
  • antibodies that bind to the same epitope as an anti-RSV antibody comprising a VH sequence of SEQ ID NO: 103 and a VL sequence of SEQ ID NO: 104 are provided.
  • the present invention provides an anti-RSV antibody comprising at least one, two, three, four, five, or six CDRs selected from the following: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 105; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 106; (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 107; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 108; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 109; and (f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 110.
  • the present invention provides an antibody comprising at least one, at least two, or all three VH CDR sequences selected from the following: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 105; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 106; and (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 107.
  • the antibody comprises a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 107.
  • the antibody comprises a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 107 and a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 110.
  • the antibody comprises a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 107, a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 110, and a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 106.
  • the antibody comprises (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 105; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 106; and (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 107.
  • the present invention provides an antibody comprising at least one, at least two, or all three VL CDR sequences selected from the group consisting of: (a) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 108; (b) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 109; and (c) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 110.
  • the antibody comprises (a) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 108; (b) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 109; and (c) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 110.
  • the antibody of the present invention comprises (a) a VH domain comprising at least one, at least two, or all three VH CDR sequences selected from the following: (i) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 105, (ii) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 106, and (iii) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 107; and (b) a VL domain comprising at least one, at least two, or all three VL CDR sequences selected from the following: (i) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 108, (ii) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 109, and (c) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 110.
  • the present invention provides an antibody comprising (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 105; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 106; (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 107; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 108; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 109; and (f) a CDR-L3 comprising an amino acid sequence selected from SEQ ID NO: 110.
  • the anti-RSV antibody is human or humanized.
  • the anti-RSV antibody comprises the CDRs as in any of the above embodiments, and further comprises an acceptor human framework, such as a human immunoglobulin framework or a human consensus framework.
  • an anti-RSV antibody comprises a heavy chain variable domain (VH) sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 111.
  • VH sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity contains substitutions (e.g., conservative substitutions), insertions, or deletions relative to the reference sequence, but the anti-RSV antibody comprising the sequence retains the ability to bind RSV.
  • the anti-RSV antibody comprises the VH sequence in SEQ ID NO: 111, including post-translational modifications of the sequence.
  • the VH comprises one, two or three CDRs selected from: (a) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 105, (b) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 106, and (c) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 107.
  • an anti-RSV antibody comprising a light chain variable domain (VL) having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 112.
  • VL sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity contains substitutions (e.g., conservative substitutions), insertions, or deletions relative to the reference sequence, but the anti-RSV antibody comprising the sequence retains the ability to bind to RSV.
  • the anti-RSV antibody comprises the VL sequence in SEQ ID NO: 112, including post-translational modifications of the sequence.
  • the VL comprises one, two or three CDRs selected from: (a) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 108; (b) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 109; and (c) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 110.
  • an anti-RSV antibody comprising a VH as in any of the embodiments provided above, and a VL as in any of the embodiments provided above.
  • the antibody comprises the VH and VL sequences in SEQ ID NO: 111 and SEQ ID NO: 112, respectively, including post-translational modifications of those sequences.
  • the present invention provides antibodies that bind to the same epitope as the anti-RSV antibodies provided herein.
  • antibodies that bind to the same epitope as an anti-RSV antibody comprising a VH sequence of SEQ ID NO: 111 and a VL sequence of SEQ ID NO: 112 are provided.
  • the present invention provides an anti-RSV antibody comprising at least one, two, three, four, five, or six CDRs selected from the following: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 113; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 114; (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 115; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 116; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 117; and (f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 118.
  • the present invention provides an antibody comprising at least one, at least two, or all three VH CDR sequences selected from the following: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 113; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 114; and (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 115.
  • the antibody comprises a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 115.
  • the antibody comprises a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 115 and a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 118.
  • the antibody comprises a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 115, a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 118, and a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 114.
  • the antibody comprises (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 113; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 114; and (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 115.
  • the present invention provides an antibody comprising at least one, at least two, or all three VL CDR sequences selected from the following: (a) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 116; (b) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 117; and (c) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 118.
  • the antibody comprises (a) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 116; (b) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 117; and (c) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 118.
  • the antibody of the present invention comprises (a) a VH domain comprising at least one, at least two, or all three VH CDR sequences selected from the following: (i) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 113, (ii) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 114, and (iii) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 115; and (b) a VL domain comprising at least one, at least two, or all three VL CDR sequences selected from the following: (i) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 116, (ii) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 117, and (c) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 118.
  • the present invention provides an antibody comprising (a) a CDR-H1 comprising an amino acid sequence of SEQ ID NO: 113; (b) a CDR-H2 comprising an amino acid sequence of SEQ ID NO: 114; (c) a CDR-H3 comprising an amino acid sequence of SEQ ID NO: 115; (d) a CDR-L1 comprising an amino acid sequence of SEQ ID NO: 116; (e) a CDR-L2 comprising an amino acid sequence of SEQ ID NO: 117; and (f) a CDR-L3 comprising an amino acid sequence selected from SEQ ID NO: 118.
  • the anti-RSV antibody is human or humanized.
  • the anti-RSV antibody comprises the CDRs as in any of the above embodiments, and further comprises an acceptor human framework, such as a human immunoglobulin framework or a human consensus framework.
  • an anti-RSV antibody comprises a heavy chain variable domain (VH) sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 119.
  • VH sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity contains substitutions (e.g., conservative substitutions), insertions, or deletions relative to the reference sequence, but the anti-RSV antibody comprising the sequence retains the ability to bind RSV.
  • a total of 1 to 10 amino acids are substituted, inserted, and/or deleted in SEQ ID NO: 119.
  • the substitutions, insertions, or deletions occur in regions outside of the CDRs (i.e., in the FRs).
  • the anti-RSV antibody comprises the VH sequence in SEQ ID NO: 119, including post-translational modifications of the sequence.
  • the VH comprises one, two or three CDRs selected from: (a) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 113, (b) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 114, and (c) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 115.
  • an anti-RSV antibody comprising a light chain variable domain (VL) having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 120.
  • VL sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity contains substitutions (e.g., conservative substitutions), insertions, or deletions relative to the reference sequence, but the anti-RSV antibody comprising the sequence retains the ability to bind to RSV.
  • the VL sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the reference sequence contains substitutions (e.g., conservative substitutions), insertions, or deletions .... NO: 120, a total of 1 to 10 amino acids are substituted, inserted and/or deleted.
  • the substitution, insertion, or deletion occurs in a region outside the CDR (i.e., in the FR).
  • the anti-RSV antibody comprises the VL sequence in SEQ ID NO: 120, including post-translational modifications of the sequence.
  • the VL comprises one, two or three CDRs selected from the following: (a) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 116; (b) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 117; and (c) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 118.
  • an anti-RSV antibody comprising a VH as in any of the embodiments provided above, and a VL as in any of the embodiments provided above.
  • the antibody comprises the VH and VL sequences in SEQ ID NO: 119 and SEQ ID NO: 120, respectively, including post-translational modifications of those sequences.
  • the present invention provides antibodies that bind to the same epitope as the anti-RSV antibodies provided herein.
  • antibodies that bind to the same epitope as an anti-RSV antibody comprising a VH sequence of SEQ ID NO: 119 and a VL sequence of SEQ ID NO: 120 are provided.
  • the present invention provides an anti-RSV antibody comprising at least one, two, three, four, five, or six CDRs selected from the following: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 121; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 122; (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 123; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 124; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 125; and (f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 126.
  • the present invention provides an antibody comprising at least one, at least two, or all three VH CDR sequences selected from the following: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 121; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 122; and (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 123.
  • the antibody comprises a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 123.
  • the antibody comprises a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 123 and a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 126.
  • the antibody comprises a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 123, a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 126, and a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 122.
  • the antibody comprises (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 121; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 122; and (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 123.
  • the present invention provides an antibody comprising at least one, at least two, or all three VL CDR sequences selected from the following: (a) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 124; (b) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 125; and (c) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 126.
  • the antibody comprises (a) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 124; (b) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 125; and (c) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 126.
  • the antibody of the present invention comprises (a) a VH domain comprising at least one, at least two, or all three VH CDR sequences selected from the following: (i) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 121, (ii) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 122, and (iii) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 123; and (b) a VL domain comprising at least one, at least two, or all three VL CDR sequences selected from the following: (i) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 124, (ii) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 125, and (c) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 126.
  • the present invention provides an antibody comprising (a) a CDR-H1 comprising an amino acid sequence of SEQ ID NO: 121; (b) a CDR-H2 comprising an amino acid sequence of SEQ ID NO: 122; (c) a CDR-H3 comprising an amino acid sequence of SEQ ID NO: 123; (d) a CDR-L1 comprising an amino acid sequence of SEQ ID NO: 124; (e) a CDR-L2 comprising an amino acid sequence of SEQ ID NO: 125; and (f) a CDR-L3 comprising an amino acid sequence selected from SEQ ID NO: 126.
  • the anti-RSV antibody is human or humanized.
  • the anti-RSV antibody comprises the CDRs as in any of the above embodiments, and further comprises an acceptor human framework, such as a human immunoglobulin framework. A frame or a person shares a framework.
  • an anti-RSV antibody comprises a heavy chain variable domain (VH) sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 127.
  • VH sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity contains substitutions (e.g., conservative substitutions), insertions, or deletions relative to the reference sequence, but the anti-RSV antibody comprising the sequence retains the ability to bind RSV.
  • a total of 1 to 10 amino acids are substituted, inserted, and/or deleted in SEQ ID NO: 127.
  • the substitutions, insertions, or deletions occur in regions outside of the CDRs (i.e., in the FRs).
  • the anti-RSV antibody comprises the VH sequence in SEQ ID NO: 127, including post-translational modifications of the sequence.
  • the VH comprises one, two or three CDRs selected from: (a) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 121, (b) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 122, and (c) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 123.
  • an anti-RSV antibody comprising a light chain variable domain (VL) having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 128.
  • VL sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity contains substitutions (e.g., conservative substitutions), insertions, or deletions relative to the reference sequence, but the anti-RSV antibody comprising the sequence retains the ability to bind to RSV.
  • a total of 1 to 10 amino acids are substituted, inserted, and/or deleted in SEQ ID NO: 128.
  • the substitution, insertion, or deletion occurs in a region outside of a CDR (i.e., in a FR).
  • the anti-RSV antibody comprises the VL sequence in SEQ ID NO: 128, including post-translational modifications of the sequence.
  • the VL comprises one, two or three CDRs selected from: (a) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 124; (b) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 125; and (c) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 126.
  • an anti-RSV antibody comprising a VH as in any of the embodiments provided above, and a VL as in any of the embodiments provided above.
  • the antibody comprises the VH and VL sequences in SEQ ID NO: 127 and SEQ ID NO: 128, respectively, including post-translational modifications of those sequences.
  • the present invention provides antibodies that bind to the same epitope as the anti-RSV antibodies provided herein.
  • antibodies that bind to the same epitope as an anti-RSV antibody comprising a VH sequence of SEQ ID NO: 127 and a VL sequence of SEQ ID NO: 128 are provided.
  • the present invention provides an anti-RSV antibody comprising at least one, two, three, four, five, or six CDRs selected from the following: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 129; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 130; (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 131; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 132; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 133; and (f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 134.
  • the present invention provides an antibody comprising at least one, at least two, or all three VH CDR sequences selected from the following: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 129; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 130; and (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 131.
  • the antibody comprises a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 131.
  • the antibody comprises a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 131 and a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 134.
  • the antibody comprises a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 131, a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 134, and a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 130.
  • the antibody comprises (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 129; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 130; and (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 131.
  • the present invention provides an antibody comprising at least one, at least two, or all three VL CDR sequences selected from the following: (a) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 132; (b) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 133; and (c) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 134.
  • the antibody comprises (a) a CDR-L1 comprising the amino acid sequence of SEQ ID NO:132; (b) a CDR-L2 comprising the amino acid sequence of SEQ ID NO:133; and (c) a CDR-L3 comprising the amino acid sequence of SEQ ID NO:134.
  • the antibody of the present invention comprises (a) a VH domain comprising at least one, at least two, or all three VH CDR sequences selected from the following: (i) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 129, (ii) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 130, and (iii) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 131; and (b) a VL domain comprising at least one, at least two, or all three VL CDR sequences selected from the following: (i) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 132, (ii) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 133, and (c) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 134.
  • the present invention provides an antibody comprising (a) a CDR-H1 comprising an amino acid sequence of SEQ ID NO: 129; (b) a CDR-H2 comprising an amino acid sequence of SEQ ID NO: 130; (c) a CDR-H3 comprising an amino acid sequence of SEQ ID NO: 131; (d) a CDR-L1 comprising an amino acid sequence of SEQ ID NO: 132; (e) a CDR-L2 comprising an amino acid sequence of SEQ ID NO: 133; and (f) a CDR-L3 comprising an amino acid sequence selected from SEQ ID NO: 134.
  • the anti-RSV antibody is human or humanized.
  • the anti-RSV antibody comprises the CDRs as in any of the above embodiments, and further comprises an acceptor human framework, such as a human immunoglobulin framework or a human consensus framework.
  • an anti-RSV antibody comprises a heavy chain variable domain (VH) sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 135.
  • VH sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity contains substitutions (e.g., conservative substitutions), insertions, or deletions relative to the reference sequence, but the anti-RSV antibody comprising the sequence retains the ability to bind RSV.
  • the anti-RSV antibody comprises the VH sequence in SEQ ID NO: 135, including post-translational modifications of the sequence.
  • the VH comprises one, two or three CDRs selected from: (a) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 129, (b) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 130, and (c) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 131.
  • an anti-RSV antibody comprising a light chain variable domain (VL) having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 136.
  • VL sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity contains substitutions (e.g., conservative substitutions), insertions, or deletions relative to the reference sequence, but the anti-RSV antibody comprising the sequence retains the ability to bind to RSV.
  • a total of 1 to 10 amino acids are substituted, inserted, and/or deleted in SEQ ID NO: 136.
  • the substitution, insertion, or deletion occurs in a region outside of a CDR (i.e., in a FR).
  • the anti-RSV antibody comprises the VL sequence in SEQ ID NO: 136, including post-translational modifications of the sequence.
  • the VL comprises one, two or three CDRs selected from: (a) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 132; (b) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 133; and (c) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 134.
  • an anti-RSV antibody comprising a VH as in any of the embodiments provided above, and a VL as in any of the embodiments provided above.
  • the antibody comprises the VH and VL sequences in SEQ ID NO: 135 and SEQ ID NO: 136, respectively, including post-translational modifications of those sequences.
  • the present invention provides antibodies that bind to the same epitope as the anti-RSV antibodies provided herein.
  • antibodies that bind to the same epitope as an anti-RSV antibody comprising a VH sequence of SEQ ID NO: 135 and a VL sequence of SEQ ID NO: 136 are provided.
  • the present invention provides an anti-RSV antibody comprising at least one, two, three, four, five, or six CDRs selected from the following: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 137; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 138; (c) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 138; (c) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 139; (d) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 140; (e) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 141; and (f) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 142.
  • the present invention provides an antibody comprising at least one, at least two, or all three VH CDR sequences selected from the following: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 137; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 138; and (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 139.
  • the antibody comprises a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 139.
  • the antibody comprises a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 139 and a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 142.
  • the antibody comprises a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 139, a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 142, and a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 138.
  • the antibody comprises (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 137; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 138; and (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 139.
  • the present invention provides an antibody comprising at least one, at least two, or all three VL CDR sequences selected from the following: (a) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 140; (b) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 141; and (c) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 142.
  • the antibody comprises (a) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 140; (b) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 141; and (c) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 142.
  • the antibody of the present invention comprises (a) a VH domain comprising at least one, at least two, or all three VH CDR sequences selected from the following: (i) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 137, (ii) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 138, and (iii) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 139; and (b) a VL domain comprising at least one, at least two, or all three VL CDR sequences selected from the following: (i) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 140, (ii) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 141, and (c) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 142.
  • the present invention provides an antibody comprising (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 137; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 138; (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 139; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 140; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 141; and (f) a CDR-L3 comprising an amino acid sequence selected from SEQ ID NO: 142.
  • the anti-RSV antibody is human or humanized.
  • the anti-RSV antibody comprises the CDRs as in any of the above embodiments, and further comprises an acceptor human framework, such as a human immunoglobulin framework or a human consensus framework.
  • an anti-RSV antibody comprises a heavy chain variable domain (VH) sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 143.
  • VH sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity contains substitutions (e.g., conservative substitutions), insertions, or deletions relative to the reference sequence, but the anti-RSV antibody comprising the sequence retains the ability to bind RSV.
  • the anti-RSV antibody comprises the VH sequence in SEQ ID NO: 143, including post-translational modifications of the sequence.
  • the VH comprises one, two or three CDRs selected from: (a) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 137, (b) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 138, and (c) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 139.
  • an anti-RSV antibody comprising an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 144.
  • the VL sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity contains substitutions (e.g., conservative substitutions), insertions, or deletions relative to the reference sequence, but the anti-RSV antibody comprising the sequence retains the ability to bind RSV.
  • a total of 1 to 10 amino acids are substituted, inserted and/or deleted in SEQ ID NO: 144.
  • the substitution, insertion, or deletion occurs in a region other than a CDR (i.e., in a FR).
  • the anti-RSV antibody comprises the VL sequence in SEQ ID NO: 144, including post-translational modifications of the sequence.
  • the VL comprises one, two or three CDRs selected from the following: (a) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 140; (b) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 141; and (c) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 142.
  • an anti-RSV antibody comprising a VH as in any of the embodiments provided above, and a VL as in any of the embodiments provided above.
  • the antibody comprises the VH and VL sequences in SEQ ID NO: 143 and SEQ ID NO: 144, respectively, including post-translational modifications of those sequences.
  • the present invention provides antibodies that bind to the same epitope as the anti-RSV antibodies provided herein.
  • antibodies that bind to the same epitope as an anti-RSV antibody comprising a VH sequence of SEQ ID NO: 143 and a VL sequence of SEQ ID NO: 144 are provided.
  • the present invention provides an anti-RSV antibody comprising at least one, two, three, four, five, or six CDRs selected from the following: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 145; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 146; (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 147; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 148; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 149; and (f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 150.
  • the present invention provides an antibody comprising at least one, at least two, or all three VH CDR sequences selected from the following: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 145; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 146; and (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 147.
  • the antibody comprises a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 147.
  • the antibody comprises a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 147 and a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 150.
  • the antibody comprises a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 147, a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 150, and a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 146.
  • the antibody comprises (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 145; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 146; and (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 147.
  • the present invention provides an antibody comprising at least one, at least two, or all three VL CDR sequences selected from the following: (a) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 148; (b) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 149; and (c) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 150.
  • the antibody comprises (a) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 148; (b) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 149; and (c) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 150.
  • the antibody of the present invention comprises (a) a VH domain comprising at least one, at least two, or all three VH CDR sequences selected from the following: (i) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 145, (ii) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 146, and (iii) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 147; and (b) a VL domain comprising at least one, at least two, or all three VL CDR sequences selected from the following: (i) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 148, (ii) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 149, and (c) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 150.
  • VH domain comprising at least one, at least two, or all three VH CDR sequences selected from the following: (i) CDR-H1 comprising
  • the present invention provides an antibody comprising (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 145; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 146; (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 147; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 148; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 149; and (f) a CDR-L3 comprising the amino acid sequence selected from SEQ ID NO: 150.
  • the anti-RSV antibody is human or humanized.
  • the anti-RSV antibody comprises the CDRs as in any of the above embodiments, and further comprises an acceptor human framework, such as a human immunoglobulin framework or a human consensus framework.
  • an anti-RSV antibody comprises a heavy chain variable domain (VH) sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 151.
  • VH sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity contains substitutions (e.g., conservative substitutions), insertions, or deletions relative to the reference sequence, but the anti-RSV antibody comprising the sequence retains the ability to bind RSV.
  • the anti-RSV antibody comprises the VH sequence in SEQ ID NO: 151, including post-translational modifications of the sequence.
  • the VH comprises one, two or three CDRs selected from: (a) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 145, (b) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 146, and (c) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 147.
  • an anti-RSV antibody comprising a light chain variable domain (VL) having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 152.
  • VL sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity contains substitutions (e.g., conservative substitutions), insertions, or deletions relative to the reference sequence, but the anti-RSV antibody comprising the sequence retains the ability to bind to RSV.
  • a total of 1 to 10 amino acids are substituted, inserted and/or deleted in SEQ ID NO: 152.
  • the substitution, insertion, or deletion occurs in a region outside of a CDR (i.e., in a FR).
  • the anti-RSV antibody comprises the VL sequence in SEQ ID NO: 152, including post-translational modifications of the sequence.
  • the VL comprises one, two or three CDRs selected from: (a) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 148; (b) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 149; and (c) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 150.
  • an anti-RSV antibody comprising a VH as in any of the embodiments provided above, and a VL as in any of the embodiments provided above.
  • the antibody comprises the VH and VL sequences in SEQ ID NO: 151 and SEQ ID NO: 152, respectively, including post-translational modifications of those sequences.
  • the present invention provides antibodies that bind to the same epitope as the anti-RSV antibodies provided herein.
  • antibodies that bind to the same epitope as an anti-RSV antibody comprising a VH sequence of SEQ ID NO: 151 and a VL sequence of SEQ ID NO: 152 are provided.
  • the present invention provides an anti-RSV antibody comprising at least one, two, three, four, five, or six CDRs selected from the following: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 153; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 154; (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 155; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 156; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 157; and (f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 158.
  • the present invention provides an antibody comprising at least one, at least two, or all three VH CDR sequences selected from the group consisting of: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 153; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 154; and (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 155.
  • the antibody comprises a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 155.
  • the antibody comprises a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 155 and a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 158. In yet another embodiment, the antibody comprises a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 155, a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 158, and a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 154.
  • the antibody comprises (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO:153; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO:154; and (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO:155.
  • the present invention provides an antibody comprising at least one, at least two, or all three VL CDR sequences selected from the following: (a) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 156; (b) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 157; and (c) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 158.
  • the antibody comprises (a) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 156; (b) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 157; and (c) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 158.
  • the antibody of the present invention comprises (a) a VH domain comprising at least one, at least two, or all three VH CDR sequences selected from the following: (i) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 153, (ii) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 154, and (iii) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 155; and (b) a VL domain comprising at least one, at least two, or all three VL CDR sequences selected from the following: (i) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 156, (ii) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 157, and (c) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 158.
  • VH domain comprising at least one, at least two, or all three VH CDR sequences selected from the following: (i) CDR-H1 compris
  • the present invention provides an antibody comprising (a) a CDR-H1 comprising an amino acid sequence of SEQ ID NO: 153; (b) a CDR-H2 comprising an amino acid sequence of SEQ ID NO: 154; (c) a CDR-H3 comprising an amino acid sequence of SEQ ID NO: 155; (d) a CDR-L1 comprising an amino acid sequence of SEQ ID NO: 156; (e) a CDR-L2 comprising an amino acid sequence of SEQ ID NO: 157; and (f) a CDR-L3 comprising an amino acid sequence selected from SEQ ID NO: 158.
  • the anti-RSV antibody is human or humanized.
  • the anti-RSV antibody comprises the CDRs as in any of the above embodiments, and further comprises an acceptor human framework, such as a human immunoglobulin framework or a human consensus framework.
  • an anti-RSV antibody comprises a heavy chain variable domain (VH) sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 159.
  • VH sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity contains substitutions (e.g., conservative substitutions), insertions, or deletions relative to the reference sequence, but the anti-RSV antibody comprising the sequence retains the ability to bind RSV.
  • a total of 1 to 10 amino acids are substituted, inserted, and/or deleted in SEQ ID NO: 159.
  • the substitutions, insertions, or deletions occur in regions outside of the CDRs (i.e., in the FRs).
  • the anti-RSV antibody comprises the VH sequence in SEQ ID NO: 159, including post-translational modifications of the sequence.
  • the VH comprises one, two or three CDRs selected from: (a) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 153, (b) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 154, and (c) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 155.
  • an anti-RSV antibody comprising a light chain variable domain (VL) having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 160.
  • VL sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity contains substitutions (e.g., conservative substitutions), insertions, or deletions relative to the reference sequence, but the anti-RSV antibody comprising the sequence retains the ability to bind to RSV.
  • the anti-RSV antibody comprises the VL sequence in SEQ ID NO: 160, including post-translational modifications of the sequence.
  • the VL comprises one, two or three CDRs selected from: (a) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 156; (b) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 157; and (c) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 158.
  • an anti-RSV antibody comprising a VH as in any of the embodiments provided above, and a VL as in any of the embodiments provided above.
  • the antibody comprises the VH and VL sequences in SEQ ID NO: 159 and SEQ ID NO: 160, respectively, including post-translational modifications of those sequences.
  • the invention provides antibodies that bind to the same epitope as the anti-RSV antibodies provided herein.
  • antibodies that bind to the same epitope as the anti-RSV antibodies provided herein are provided.
  • the anti-RSV antibodies in the column bind to the same epitope.
  • the present invention provides an anti-RSV antibody comprising at least one, two, three, four, five, or six CDRs selected from the following: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 161; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 162; (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 163; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 164; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 165; and (f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 166.
  • the present invention provides an antibody comprising at least one, at least two, or all three VH CDR sequences selected from the following: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 161; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 162; and (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 163.
  • the antibody comprises a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 163.
  • the antibody comprises a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 163 and a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 166.
  • the antibody comprises a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 163, a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 166, and a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 162.
  • the antibody comprises (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 161; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 162; and (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 163.
  • the present invention provides an antibody comprising at least one, at least two, or all three VL CDR sequences selected from the following: (a) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 164; (b) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 165; and (c) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 166.
  • the antibody comprises (a) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 164; (b) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 165; and (c) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 166.
  • the antibody of the present invention comprises (a) a VH domain comprising at least one, at least two, or all three VH CDR sequences selected from the following: (i) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 161, (ii) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 162, and (iii) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 163; and (b) a VL domain comprising at least one, at least two, or all three VL CDR sequences selected from the following: (i) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 164, (ii) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 165, and (c) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 166.
  • the present invention provides an antibody comprising (a) a CDR-H1 comprising an amino acid sequence of SEQ ID NO: 161; (b) a CDR-H2 comprising an amino acid sequence of SEQ ID NO: 162; (c) a CDR-H3 comprising an amino acid sequence of SEQ ID NO: 163; (d) a CDR-L1 comprising an amino acid sequence of SEQ ID NO: 164; (e) a CDR-L2 comprising an amino acid sequence of SEQ ID NO: 165; and (f) a CDR-L3 comprising an amino acid sequence selected from SEQ ID NO: 166.
  • the anti-RSV antibody is human or humanized.
  • the anti-RSV antibody comprises the CDRs as in any of the above embodiments, and further comprises an acceptor human framework, such as a human immunoglobulin framework or a human consensus framework.
  • the anti-RSV antibody comprises a heavy chain variable domain (VH) sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 167.
  • VH sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity contains substitutions (e.g., conservative substitutions), insertions, or deletions relative to the reference sequence, but the anti-RSV antibody comprising the sequence retains the ability to bind to RSV.
  • the anti-RSV antibody comprises the VH sequence in SEQ ID NO: 167, including post-translational modifications of the sequence.
  • the VH comprises one, two or three CDRs selected from the group consisting of: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 161, (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 162. sequence, and (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO:163.
  • an anti-RSV antibody comprising a light chain variable domain (VL) having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 168.
  • VL sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity contains substitutions (e.g., conservative substitutions), insertions, or deletions relative to the reference sequence, but the anti-RSV antibody comprising the sequence retains the ability to bind to RSV.
  • a total of 1 to 10 amino acids are substituted, inserted and/or deleted in SEQ ID NO: 168.
  • the substitution, insertion, or deletion occurs in a region outside of a CDR (i.e., in a FR).
  • the anti-RSV antibody comprises the VL sequence in SEQ ID NO: 168, including post-translational modifications of the sequence.
  • the VL comprises one, two or three CDRs selected from: (a) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 164; (b) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 165; and (c) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 166.
  • an anti-RSV antibody comprising a VH as in any of the embodiments provided above, and a VL as in any of the embodiments provided above.
  • the antibody comprises the VH and VL sequences in SEQ ID NO: 167 and SEQ ID NO: 168, respectively, including post-translational modifications of those sequences.
  • the present invention provides antibodies that bind to the same epitope as the anti-RSV antibodies provided herein.
  • antibodies that bind to the same epitope as an anti-RSV antibody comprising a VH sequence of SEQ ID NO: 167 and a VL sequence of SEQ ID NO: 168 are provided.
  • the present invention provides an anti-RSV antibody comprising at least one, two, three, four, five, or six CDRs selected from the following: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 169; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 170; (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 171; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 172; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 173; and (f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 174.
  • the present invention provides an antibody comprising at least one, at least two, or all three VH CDR sequences selected from the following: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 169; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 170; and (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 171.
  • the antibody comprises a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 171.
  • the antibody comprises a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 171 and a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 174.
  • the antibody comprises a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 171, a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 174, and a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 170.
  • the antibody comprises (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 169; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 170; and (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 171.
  • the present invention provides an antibody comprising at least one, at least two, or all three VL CDR sequences selected from the following: (a) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 172; (b) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 173; and (c) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 174.
  • the antibody comprises (a) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 172; (b) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 173; and (c) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 174.
  • the antibody of the present invention comprises (a) a VH domain comprising at least one, at least two, or all three VH CDR sequences selected from the following: (i) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 169, (ii) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 170, and (iii) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 171; and (b) a VL domain comprising at least one, at least two, or all three VL CDR sequences selected from the following: (i) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 172, (ii) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 173, and (c) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 174.
  • the present invention provides an antibody comprising (a) an amino acid sequence comprising SEQ ID NO: 169 (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 170; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 170; (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 171; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 172; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 173; and (f) a CDR-L3 comprising an amino acid sequence selected from SEQ ID NO: 174.
  • the anti-RSV antibody is human or humanized.
  • the anti-RSV antibody comprises the CDRs as in any of the above embodiments, and further comprises an acceptor human framework, such as a human immunoglobulin framework or a human consensus framework.
  • an anti-RSV antibody comprises a heavy chain variable domain (VH) sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 175.
  • VH sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity contains substitutions (e.g., conservative substitutions), insertions, or deletions relative to the reference sequence, but the anti-RSV antibody comprising the sequence retains the ability to bind RSV.
  • the anti-RSV antibody comprises the VH sequence in SEQ ID NO: 175, including post-translational modifications of the sequence.
  • the VH comprises one, two or three CDRs selected from: (a) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 169, (b) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 170, and (c) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 171.
  • an anti-RSV antibody comprising a light chain variable domain (VL) having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 176.
  • VL sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity contains substitutions (e.g., conservative substitutions), insertions, or deletions relative to the reference sequence, but the anti-RSV antibody comprising the sequence retains the ability to bind to RSV.
  • a total of 1 to 10 amino acids are substituted, inserted and/or deleted in SEQ ID NO: 176.
  • the substitution, insertion, or deletion occurs in a region outside of a CDR (i.e., in a FR).
  • the anti-RSV antibody comprises the VL sequence in SEQ ID NO: 176, including post-translational modifications of the sequence.
  • the VL comprises one, two or three CDRs selected from: (a) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 72; (b) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 173; and (c) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 174.
  • an anti-RSV antibody comprising a VH as in any of the embodiments provided above, and a VL as in any of the embodiments provided above.
  • the antibody comprises the VH and VL sequences in SEQ ID NO: 175 and SEQ ID NO: 176, respectively, including post-translational modifications of those sequences.
  • the present invention provides antibodies that bind to the same epitope as the anti-RSV antibodies provided herein.
  • antibodies that bind to the same epitope as an anti-RSV antibody comprising a VH sequence of SEQ ID NO: 175 and a VL sequence of SEQ ID NO: 176 are provided.
  • the present invention provides an anti-RSV antibody comprising at least one, two, three, four, five, or six CDRs selected from the following: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 177; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 178; (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 179; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 180; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 181; and (f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 182.
  • the present invention provides an antibody comprising at least one, at least two, or all three VH CDR sequences selected from the group consisting of: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 177; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 178; and (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 179.
  • the antibody comprises a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 179.
  • the antibody comprises a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 179 and a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 182.
  • the antibody comprises a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 179, a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 182, and a CDR-H4 comprising the amino acid sequence of SEQ ID NO: 183.
  • the antibody comprises (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 177; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 178; and (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 179.
  • the present invention provides an antibody comprising at least one, at least two, or all three VL CDR sequences selected from the following: (a) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 180; (b) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 181; and (c) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 182.
  • the antibody comprises (a) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 180; (b) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 181; and (c) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 182.
  • the antibody of the present invention comprises (a) a VH domain comprising at least one, at least two, or all three VH CDR sequences selected from the following: (i) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 177, (ii) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 178, and (iii) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 179; and (b) a VL domain comprising at least one, at least two, or all three VL CDR sequences selected from the following: (i) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 180, (ii) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 181, and (c) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 182.
  • the present invention provides an antibody comprising (a) a CDR-H1 comprising an amino acid sequence of SEQ ID NO: 177; (b) a CDR-H2 comprising an amino acid sequence of SEQ ID NO: 178; (c) a CDR-H3 comprising an amino acid sequence of SEQ ID NO: 179; (d) a CDR-L1 comprising an amino acid sequence of SEQ ID NO: 180; (e) a CDR-L2 comprising an amino acid sequence of SEQ ID NO: 181; and (f) a CDR-L3 comprising an amino acid sequence selected from SEQ ID NO: 182.
  • the anti-RSV antibody is human or humanized.
  • the anti-RSV antibody comprises the CDRs as in any of the above embodiments, and further comprises an acceptor human framework, such as a human immunoglobulin framework or a human consensus framework.
  • an anti-RSV antibody comprises a heavy chain variable domain (VH) sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 183.
  • VH sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity contains substitutions (e.g., conservative substitutions), insertions, or deletions relative to the reference sequence, but the anti-RSV antibody comprising the sequence retains the ability to bind RSV.
  • the anti-RSV antibody comprises the VH sequence in SEQ ID NO: 183, including post-translational modifications of the sequence.
  • the VH comprises one, two or three CDRs selected from: (a) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 177, (b) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 178, and (c) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 179.
  • an anti-RSV antibody comprising a light chain variable domain (VL) having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 184.
  • VL sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity contains substitutions (e.g., conservative substitutions), insertions, or deletions relative to the reference sequence, but the anti-RSV antibody comprising the sequence retains the ability to bind to RSV.
  • the anti-RSV antibody comprises the VL sequence in SEQ ID NO: 184, including post-translational modifications of the sequence.
  • the VL comprises one, two or three CDRs selected from: (a) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 180; (b) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 181; and (c) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 182.
  • an anti-RSV antibody comprising a VH as in any of the embodiments provided above, and a VL as in any of the embodiments provided above.
  • the antibody comprises The VH and VL sequences in SEQ ID NO: 183 and SEQ ID NO: 184, including post-translational modifications of those sequences.
  • the present invention provides antibodies that bind to the same epitope as the anti-RSV antibodies provided herein.
  • antibodies that bind to the same epitope as an anti-RSV antibody comprising a VH sequence of SEQ ID NO: 183 and a VL sequence of SEQ ID NO: 184 are provided.
  • the present invention provides an anti-RSV antibody comprising at least one, two, three, four, five, or six CDRs selected from the following: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 185; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 186; (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 187; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 188; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 189; and (f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 190.
  • the present invention provides an antibody comprising at least one, at least two, or all three VH CDR sequences selected from the following: (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 185; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 186; and (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 187.
  • the antibody comprises a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 187.
  • the antibody comprises a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 187 and a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 190.
  • the antibody comprises a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 187, a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 190, and a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 186.
  • the antibody comprises (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 185; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 186; and (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 187.
  • the present invention provides an antibody comprising at least one, at least two, or all three VL CDR sequences selected from the following: (a) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 188; (b) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 189; and (c) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 190.
  • the antibody comprises (a) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 188; (b) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 189; and (c) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 190.
  • the antibody of the present invention comprises (a) a VH domain comprising at least one, at least two, or all three VH CDR sequences selected from the following: (i) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 185, (ii) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 186, and (iii) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 187; and (b) a VL domain comprising at least one, at least two, or all three VL CDR sequences selected from the following: (i) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 188, (ii) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 189, and (c) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 190.
  • the present invention provides an antibody comprising (a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 185; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 186; (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 187; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 188; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 189; and (f) a CDR-L3 comprising an amino acid sequence selected from SEQ ID NO: 190.
  • the anti-RSV antibody is human or humanized.
  • the anti-RSV antibody comprises the CDRs as in any of the above embodiments, and further comprises an acceptor human framework, such as a human immunoglobulin framework or a human consensus framework.
  • the anti-RSV antibody comprises a heavy chain variable domain (VH) sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 191.
  • VH sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity contains substitutions (e.g., conservative substitutions), insertions, or deletions relative to the reference sequence, but the anti-RSV antibody comprising the sequence retains the ability to bind to RSV.
  • the anti-RSV antibody comprises the VH sequence in SEQ ID NO: 191, including post-translational modifications of the sequence.
  • the VH comprises one, two or three CDRs selected from the following: (a) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 185, (b) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 186, and (c) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 187.
  • an anti-RSV antibody comprising a light chain variable domain (VL) having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 192.
  • VL sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity contains substitutions (e.g., conservative substitutions), insertions, or deletions relative to the reference sequence, but the anti-RSV antibody comprising the sequence retains the ability to bind to RSV.
  • a total of 1 to 10 amino acids are substituted, inserted, and/or deleted in SEQ ID NO: 192.
  • the substitution, insertion, or deletion occurs in a region outside of a CDR (i.e., in a FR).
  • the anti-RSV antibody comprises the VL sequence in SEQ ID NO: 192, including post-translational modifications of the sequence.
  • the VL comprises one, two or three CDRs selected from: (a) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 188; (b) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 189; and (c) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 190.
  • an anti-RSV antibody comprising a VH as in any of the embodiments provided above, and a VL as in any of the embodiments provided above.
  • the antibody comprises the VH and VL sequences in SEQ ID NO: 191 and SEQ ID NO: 192, respectively, including post-translational modifications of those sequences.
  • the present invention provides antibodies that bind to the same epitope as the anti-RSV antibodies provided herein.
  • antibodies that bind to the same epitope as the anti-RSV antibodies comprising the VH sequence of SEQ ID NO: 191 and the VL sequence of SEQ ID NO: 192 are provided.
  • the anti-RSV antibody is a monoclonal antibody, including chimeric, humanized or human antibodies.
  • the anti-RSV antibody is an antibody fragment, such as Fv, Fab, Fab', xFab, scFv, diabody, or F(ab') 2 fragment.
  • the antibody is a full-length antibody, such as having replacement L234A, L235A and P329G (LALA-PG) in the Fc region derived from the human IgG1 Fc region (see, e.g., WO2012/130831 A1).
  • an anti-RSV antibody may incorporate any of the features described in Sections 1-7 below, singly or in combination:
  • an antibody provided herein has a dissociation constant (Kd) of ⁇ 1 ⁇ M, ⁇ 100 nM, ⁇ 10 nM, ⁇ 1 nM, ⁇ 0.1 nM, ⁇ 0.01 nM, or ⁇ 0.001 nM (e.g., 10 ⁇ 8 M or less, e.g., 10 ⁇ 8 M to 10 ⁇ 13 M, e.g., 10 ⁇ 9 M to 10 ⁇ 13 M).
  • Kd dissociation constant
  • Kd is measured by a radiolabeled antigen binding assay (RIA).
  • RIA radiolabeled antigen binding assay
  • an RIA is performed with the antibody of interest in Fab form and its antigen.
  • the solution binding affinity of the Fab for the antigen is measured by equilibrating the Fab with a minimal concentration of ( 125I )-labeled antigen in the presence of a titration series of unlabeled antigen and then capturing bound antigen with an anti-Fab antibody-coated plate (see, e.g., Chen et al., J. Mol. Biol. 293:865-881 (1999)).
  • Multiwell plates (Thermo Scientific) are coated overnight with 5 ⁇ g/ml capture anti-Fab antibody (Cappel Labs) in 50 mM sodium carbonate (pH 9.6) and subsequently blocked with 2% (w/v) bovine serum albumin in PBS for 2-5 hours at room temperature (about 23°C).
  • 100 pM or 26 pM [ 125I ]-antigen is mixed with serial dilutions of the Fab of interest (e.g., consistent with the evaluation of the anti-VEGF antibody, Fab-12 in Presta et al., Cancer Res. 57:4593-4599 (1997)).
  • the Fab of interest is then incubated overnight; however, the incubation can be continued for longer (e.g., about 65 hours) to ensure that equilibrium is reached. Thereafter, the mixture is transferred to the capture plate and incubated at room temperature (e.g., 1 hour). The solution is then removed and the plate is incubated with 0.1% polysorbate 20 in PBS. The plates were washed 8 times. After the plates were dried, 150 ⁇ l/well of scintillation fluid (MICROSCINT-20 TM ; Packard) was added and the plates were counted for 10 minutes on a TOPCOUNT TM gamma counter (Packard). The concentration of each Fab that gave less than or equal to 20% of maximal binding was selected for competitive binding assays.
  • MICROSCINT-20 TM scintillation fluid
  • Kd is calculated using For example, at 25°C using an immobilized antigen CM5 chip at approximately 10 response units (RU) or (BIAcore, Inc., Piscataway, NJ) performed the assay.
  • CM5 chip at approximately 10 response units (RU) or (BIAcore, Inc., Piscataway, NJ) performed the assay.
  • a carboxymethylated dextran biosensor chip (CM5, BIACORE, Inc.) was activated with N-ethyl-N'-(3-dimethylaminopropyl)-carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS) according to the supplier's instructions.
  • EDC N-ethyl-N'-(3-dimethylaminopropyl)-carbodiimide hydrochloride
  • NHS N-hydroxysuccinimide
  • Antigen was diluted to 5 ⁇ g/ml (about 0.2 ⁇ M) with 10 mM sodium acetate pH 4.8 and then injected at a flow rate of 5 ⁇ l/min to obtain about 10 response units (RU) of coupled protein. After the injection of antigen, 1 M ethanolamine was injected to block unreacted groups. For kinetic measurements, two-fold serial dilutions of Fab (0.78 nM to 500 nM) in PBS (PBST) containing 0.05% polysorbate 20 (TWEEN-20 TM ) surfactant were injected at a flow rate of about 25 ⁇ l/min at 25°C.
  • PBST PBS
  • TWEEN-20 TM polysorbate 20
  • association rate (k on ) and dissociation rate (k off ) are calculated by simultaneously fitting the association and dissociation sensorgrams using the ELISA software version 3.2.
  • the equilibrium dissociation constant (Kd) is calculated as the ratio k off / kon . See, e.g., Chen et al., J. Mol. Biol. 293: 865-881 (1999).
  • a spectrometer such as a spectrophotometer equipped with a cut-off device (Aviv Instruments) or a 8000 series SLM-AMINCO TM spectrophotometer (ThermoSpectronic) with a stirred cuvette at 25°C.
  • the antibodies provided herein are antibody fragments.
  • antibody fragment refers to a molecule other than an intact antibody that contains a portion of an intact antibody that retains the ability to specifically bind to an antigen.
  • Antibody fragments include, but are not limited to, Fab, Fab', Fab'SH, F(ab') 2 , xFab, Fv, single-chain Fab (scFab), single-chain variable fragment (scFv) and single-domain antibodies (dAb).
  • the antibody fragment is a Fab, Fab', Fab'SH, xFab, or F(ab') 2 fragment, in particular a Fab fragment.
  • Papain digestion of an intact antibody produces two identical antigen-binding fragments, called "Fab” fragments, each containing a heavy and light chain variable domain and a constant domain of the light chain and the first constant domain (CH1) of the heavy chain. Therefore, the term "Fab fragment” refers to an antibody fragment comprising a light chain fragment including the VL domain and the constant domain (CL) of the light chain, and the VH domain and the first constant domain (CH1) of the heavy chain.
  • xFab fragment refers to a Fab fragment in which the VH domain is exchanged with the VL domain or the CH1 domain is exchanged with the CL domain.
  • the Fab' fragment differs from the Fab fragment by the addition of residues at the carboxyl terminus of the heavy chain CH1 domain, including one or more cysteines from the hinge region of the antibody.
  • Fab'-SH is a Fab' fragment in which the cysteine residues of the constant domain have free sulfhydryl groups.
  • Pepsin treatment produces a F(ab') 2 fragment having two antigen-binding sites (two Fab fragments) and a portion of the Fc region.
  • the antibody fragment is a diabody, a triabody or a tetrabody.
  • Diabodies are antibody fragments with two antigen binding sites that can be bivalent or bispecific. See, for example, EP 404,097; WO 1993/01161; Hudson et al., Nat. Med. 9: 129-134 (2003); and Hollinger et al., Proc. Natl. Acad. Sci. USA 90: 6444-6448 (1993). Triabodies and tetrabodies are also described in Hudson et al., Nat. Med. 9: 129-134 (2003).
  • the antibody fragment is a single-chain Fab fragment.
  • Single-chain Fab fragment or “scFab” is a polypeptide consisting of an antibody heavy chain variable domain (VH), an antibody constant domain 1 (CH1), an antibody light chain variable domain (VL), an antibody light chain constant domain (CL) and a linker, wherein the antibody domain and the linker have one of the following orders in the N-terminal to C-terminal direction: a) VH-CH1-linker-VL-CL, b) VL-CL-linker-VH-CH1, c) VH-CL-linker-VL-CH1 or d) VL-CH1-linker-VH-CL.
  • the linker is a polypeptide having at least 30 amino acids, preferably between 32 and 50 amino acids.
  • the single-chain Fab fragment is stabilized via a natural disulfide bond between the CL domain and the CH1 domain.
  • interchain bonds are generated by inserting cysteine residues (e.g., position 44 in the variable heavy chain and position 100 in the variable light chain according to Kabat numbering). These single-chain Fab molecules can be further stabilized by disulfide bonds.
  • the antibody fragment is a single chain variable fragment (scFv).
  • scFv single chain variable fragment
  • a "single chain variable fragment (scFv)" is a fusion protein of the heavy chain variable region ( VH ) and the light chain variable region ( VL ) of an antibody connected by a linker.
  • the linker is a short polypeptide of 10 to 25 amino acids and is generally rich in glycine for flexibility, and serine or threonine for solubility, and can connect the N-terminus of VH to the C-terminus of VL , or vice versa. Despite the removal of the constant region and the introduction of the linker, this protein retains the specificity of the original antibody.
  • the antibody fragment is a single domain antibody.
  • a single domain antibody is an antibody fragment that contains all or part of the heavy chain variable domain or all or part of the light chain variable domain of an antibody.
  • the single domain antibody is a human single domain antibody (Domantis, Inc., Waltham, MA; see, e.g., U.S. Patent No. 6,248,516 B1).
  • Antibody fragments can be produced by a variety of techniques, including but not limited to proteolytic digestion of intact antibodies and production in recombinant host cells (eg, E. coli or phage), as described herein.
  • recombinant host cells eg, E. coli or phage
  • the antibodies provided herein are chimeric antibodies.
  • Certain chimeric antibodies are described, for example, in U.S. Pat. No. 4,816,567; and Morrison et al., Proc. Natl. Acad. Sci. USA, 81: 6851-6855 (1984).
  • a chimeric antibody comprises a non-human variable region (e.g., a variable region derived from a mouse, rat, hamster, rabbit, or non-human primate, such as a monkey) and a human constant region.
  • a chimeric antibody is a "class-switched" antibody in which the class or subclass has been changed from the class or subclass of the parent antibody. Chimeric antibodies include antigen-binding fragments thereof.
  • chimeric antibodies are humanized antibodies.
  • non-human antibodies are humanized to reduce immunogenicity to people while retaining the specificity and affinity of the parent non-human antibodies.
  • humanized antibodies include one or more variable domains, wherein HVR, such as CDR (or a portion thereof) are derived from non-human antibodies, and FR (or a portion thereof) are derived from human antibody sequences.
  • HVR such as CDR (or a portion thereof) are derived from non-human antibodies
  • FR or a portion thereof
  • humanized antibodies also include at least a portion of human constant regions.
  • some FR residues in humanized antibodies are replaced with corresponding residues from non-human antibodies (e.g., antibodies derived from HVR residues), for example, to restore or improve antibody specificity or affinity.
  • Human framework regions that can be used for humanization include, but are not limited to, framework regions selected using the "best-fit" method (see, e.g., Sims et al., J. Immunol. 151: 2296 (1993)); framework regions derived from the consensus sequence of human antibodies of a specific subgroup of light or heavy chain variable regions (see, e.g., Carter et al. Proc. Natl. Acad. Sci. USA, 89: 4285 (1992); and Presta et al., J. Immunol., 151: 262). 3 (1993)); human mature (somatically mutated) framework regions or human germline framework regions (see, e.g., Almagro and Fransson, Front. Biosci.
  • the antibodies provided herein are human antibodies.
  • Human antibodies can be generated using a variety of techniques known in the art. Generally, human antibodies are described in van Dijk and van de Winkel, Curr. Opin. Pharmacol. 5: 368-74 (2001) and Lonberg, Curr. Opin. Immunol. 20: 450-459 (2008).
  • Human antibodies can be prepared by administering an immunogen to a transgenic animal that has been modified to produce intact human antibodies or intact antibodies with human variable regions in response to an antigenic challenge.
  • Such animals typically contain all or part of the human immunoglobulin loci, which replace the endogenous immunoglobulin loci, or which are present extrachromosomally or randomly integrated into the chromosomes of the animal. In such transgenic mice, the endogenous immunoglobulin loci have generally been inactivated.
  • Human antibodies can also be generated by hybridoma-based methods.
  • Human myeloma and mouse-human heteromyeloma cell lines for generating human monoclonal antibodies have been described (see, e.g., Kozbor, J. Immunol., 133: 3001 (1984); Brodeur et al., Monoclonal Antibody Production Techniques and Applications, pp. 51-63 (Marcel Dekker, Inc., New York, 1987); and Boerner et al., J. Immunol., 147: 86 (1991)).
  • Human antibodies generated via human B cell hybridoma technology are also described in Li et al., Proc. Natl. Acad. Sci. USA, 103: 3557-3562 (2006).
  • variable domain sequences selected from the phage display library derived from humans can be combined with desired human constant domains.
  • the technology of selecting human antibodies from antibody libraries is described below.
  • the antibodies of the invention can be isolated by screening combinatorial libraries for antibodies having one or more desired activities. Methods for screening combinatorial libraries are reviewed in, for example, Lerner et al., Nature Reviews 16: 498-508 (2016). For example, a variety of methods for generating phage display libraries and screening such libraries for antibodies having desired binding characteristics are known in the art.
  • phage display methods repertoires of VH and VL genes are cloned separately by polymerase chain reaction (PCR) and randomly recombined in phage libraries, which can then be screened for antigen-binding phage, as described in Winter et al., Annual Review of Immunology 12: 433-455 (1994). Phage typically display antibody fragments as single-chain Fv (scFv) fragments or as Fab fragments. Libraries from immunized sources provide high-affinity antibodies to the immunogen without the need to construct hybridomas.
  • PCR polymerase chain reaction
  • non-immune repertoires can be cloned (e.g., from humans) to provide a single source of antibodies to a large number of non-self and also self-antigens without any immunization, as described by Griffiths et al., EMBO Journal 12: 725-734 (1993).
  • naive libraries can also be generated synthetically by cloning unrearranged V gene segments from stem cells and using PCR primers containing random sequences encoding the highly variable CDR3 regions and achieving rearrangement in vitro, as described by Hoogenboom and Winter, Journal of Molecular Biology 227:381-388 (1992).
  • Patent publications describing human antibody phage libraries include, for example: U.S. Patent Nos. 5,750,373; 7,985,840; 7,785,903 and 8,679,490 and U.S. Patent Publication Nos. 2005/0079574, 2007/0117126, 2007/0237764 and 2007/0292936.
  • the invention relates to methods for displaying antibodies on surfaces of yeast, including ribosomes and mRNA, and methods for displaying and selecting antibodies on bacteria, mammalian cells, insect cells or yeast cells.
  • Methods for displaying antibodies on surfaces of yeast are reviewed in, for example, Scholler et al., Methods in Molecular Biology 503: 135-56 (2012) and Cherf et al., Methods in Molecular biology 1319: 155-175 (2015) and Zhao et al., Methods in Molecular Biology 889: 73-84 (2012).
  • Methods for displaying antibodies on surfaces of yeast are described in, for example, He et al., Nucleic Acids Research 25: 5132-5134 (1997) and Hanes et al., PNAS 94: 4937-4942 (1997).
  • Antibodies or antibody fragments isolated from human antibody libraries are considered human antibodies or human antibody fragments herein.
  • the antibody provided herein is a multispecific antibody, such as a bispecific antibody.
  • a multispecific antibody is a monoclonal antibody that has binding specificity to at least two different sites (i.e., different epitopes on different antigens or different epitopes on the same antigen).
  • a multispecific antibody has three or more binding specificities.
  • one of the binding specificities is for RSV, and the other (two or more) specificities are for any other antigen.
  • a bispecific antibody can be combined with two (or more) different antigens or epitopes of RSV. It is also possible to use multispecific (e.g., bispecific) antibodies to localize cytotoxic agents or cells to cells infected with RSV. Multispecific antibodies can be prepared with full-length antibodies or antibody fragments.
  • Techniques for generating multispecific antibodies include, but are not limited to, recombinant co-expression of two pairs of immunoglobulin heavy chain-light chains with different specificities (see Milstein and Cuello, Nature, 305:537 (1983)), and “knob-into-hole” engineering (see, for example, U.S. Pat. No. 5,731,168 and Atwell et al., J. Mol. Biol. 270:26 (1997)). It is also possible to generate antibody Fc-heterodimer molecules through engineered electrostatic manipulation effects (see, e.g., WO 2009/089004); cross-link two or more antibodies or fragments (see, e.g., U.S. Patent No.
  • engineered antibodies with three or more antigen binding sites including, for example, "octopus antibodies” or DVD-Igs (see, for example, WO 2001/77342 and WO 2008/024715).
  • multispecific antibodies with three or more antigen binding sites can be found in WO 2010/115589, WO 2010/112193, WO 2010/136172, WO 2010/145792, and WO 2013/026831.
  • Bispecific antibodies or antigen-binding fragments thereof also include "dual-acting FAbs" or "DAFs” that contain antigen binding sites that bind to RSV and another different antigen, or two different epitopes of RSV (see, for example, US 2008/0069820 and WO 2015/095539).
  • the multispecific antibodies may also be provided in an asymmetric form with domain exchange in one or more binding arms with the same antigen specificity, i.e. by exchanging VH/VL domains (see, e.g., WO 2009/080252 and WO 2015/150447), CH1/CL domains (see, e.g., WO 2009/080253) or entire Fab arms (see, e.g., WO 2009/080251, WO 2016/016299, see also Schaefer et al., PNAS, 108 (2011) 1187-1191, and Klein et al., MAbs 8 (2016) 1010-20).
  • the multispecific antibodies comprise crossover Fab fragments.
  • crossover Fab fragment or "xFab fragment” or “exchange Fab fragment” refers to a Fab fragment in which the variable regions or constant regions of the heavy and light chains are exchanged.
  • the crossover Fab fragments comprise a polypeptide chain consisting of a light chain variable region (VL) and a heavy chain constant region (CH1), and a polypeptide chain consisting of a heavy chain variable region (VH) and a light chain constant region (CL).
  • Asymmetric Fab arms can also be engineered by introducing charged or uncharged amino acid mutations into the domain interface to direct correct Fab pairing. See, e.g., WO 2016/172485.
  • amino acid sequence variants of the antibodies provided herein are contemplated. For example, it may be desirable to improve The binding affinity and/or other biological properties of the antibody.
  • Amino acid sequence variants of the antibody can be prepared by introducing suitable modifications into the nucleotide sequence encoding the antibody, or by peptide synthesis. Such modifications include, for example, deletions of residues in the amino acid sequence of the antibody, and/or insertions and/or substitutions. Any combination of deletions, insertions, and substitutions can be performed to obtain the final construct, as long as the final construct has the desired characteristics, such as antigen binding.
  • antibody variants with one or more amino acid substitutions are provided.
  • Sites of interest for substitution mutagenesis include HVR and FR.
  • Conservative substitutions are shown in Table A under the heading "Preferred Substitutions”. More substantial changes are provided in Table A under the heading "Exemplary Substitutions” and are further described below with reference to amino acid side chain classes.
  • Amino acid substitutions can be introduced into the antibody of interest, and the product can be screened for desired activity, such as retained/improved antigen binding, reduced immunogenicity, or improved ADCC or CDC.
  • Amino acids can be grouped according to common side chain properties as follows:
  • Non-conservative substitutions will entail exchanging a member of one of these classes for a member of another class.
  • substitutional variants involves replacing one or more hypervariable region residues of a parent antibody (e.g., a humanized or human antibody).
  • a parent antibody e.g., a humanized or human antibody.
  • the resulting variants selected for further study will have changes (e.g., improvements) in certain biological properties relative to the parent antibody (e.g., increased affinity, reduced immunogenicity) and/or will substantially retain certain biological properties of the parent antibody.
  • An exemplary substitutional variant is an affinity-matured antibody, which can be conveniently generated, for example, using phage display-based affinity maturation techniques such as those described herein.
  • one or more HVRs are replaced. The residues are mutated and the variant antibodies are displayed on phage and screened for a particular biological activity (eg, binding affinity).
  • Changes may be made to HVRs, for example, to improve antibody affinity.
  • Such changes may be made to HVR "hot spots,” residues encoded by codons that undergo mutations at high frequency during the somatic maturation process (see, e.g., Chowdhury, Methods Mol. Biol. 207: 179-196 (2008)), and/or residues that contact antigen, wherein the resulting variant VH or VL is tested for binding affinity.
  • affinity maturation by construction and reselection of secondary libraries has been described, for example, in Hoogenboom et al., in Methods in Molecular Biology 178: 1-37 (O'Brien et al., eds., Human Press, Totowa, NJ, (2001)).
  • affinity maturation diversity is introduced into variable genes selected for maturation by any of a variety of methods (e.g., error-prone PCR, chain shuffling, or oligonucleotide-directed mutagenesis). Then, a secondary library is created. The library is then screened to identify any antibody variants with the desired affinity.
  • HVR-guided approach involves an HVR-guided approach in which several HVR residues (e.g., 4-6 residues at a time) are randomized.
  • HVR residues involved in antigen binding can be specifically identified, for example, using alanine scanning mutagenesis or modeling.
  • CDR-H3 and CDR-L3 are often targeted.
  • substitutions, insertions, or deletions may occur within one or more HVRs, as long as such changes do not substantially reduce the ability of the antibody to bind to antigen.
  • conservative changes e.g., conservative substitutions, as provided herein
  • HVRs that do not substantially reduce binding affinity.
  • Such changes may be, for example, outside the antigen contact residues in HVRs.
  • each HVR is unchanged or contains no more than 1, 2 or 3 amino acid substitutions.
  • alanine scanning mutagenesis One method that can be used to identify residues or regions in an antibody that can be targeted for mutagenesis is called “alanine scanning mutagenesis," as described by Cunningham and Wells (1989) Science, 244: 1081-1085.
  • a residue or a group of target residues e.g., charged residues such as Arg, Asp, His, Lys, and Glu
  • neutral or negatively charged amino acids e.g., alanine or polyalanine
  • Further substitutions can be introduced at amino acid positions that show functional sensitivity to the initial substitutions.
  • the crystal structure of the antigen-antibody complex is used to identify contact points between the antibody and the antigen. Such contact residues and neighboring residues can be targeted or eliminated as candidates for substitution.
  • Variants can be screened to determine whether they contain the desired properties.
  • Amino acid sequence insertions include amino and/or carboxyl terminal fusions ranging in length from 1 residue to polypeptides containing 100 or more residues, and intrasequence insertions of single or multiple amino acid residues.
  • terminal insertions include antibodies with an N-terminal methionyl residue.
  • Other insertion variants of antibody molecules include fusions of the N or C-terminal of an antibody with an enzyme (e.g., for ADEPT) or a polypeptide that prolongs the serum half-life of the antibody.
  • the antibodies provided herein are altered to increase or decrease the degree of antibody glycosylation.
  • the addition or deletion of glycosylation sites of an antibody can be conveniently achieved by altering the amino acid sequence so as to create or eliminate one or more glycosylation sites.
  • the oligosaccharides attached to it can be altered.
  • Natural antibodies produced by mammalian cells typically contain branched, biantennary oligosaccharides that are generally attached to Asn297 of the CH2 domain of the Fc region via an N-link. See, e.g., Wright et al., TIBTECH 15:26-32 (1997).
  • Oligosaccharides can include various carbohydrates, such as mannose, N-acetylglucosamine (GlcNAc), galactose, and sialic acid, as well as fucose attached to the GlcNAc in the "trunk" of the biantennary oligosaccharide structure.
  • the oligosaccharides in the antibodies of the invention can be modified to create antibody variants with certain improved properties.
  • antibody variants are provided that have non-fucosylated oligosaccharides, i.e., oligosaccharide structures lacking fucose, attached (directly or indirectly) to the Fc region.
  • non-fucosylated oligosaccharides also referred to as "afucosylated” oligosaccharides
  • antibody variants are provided that have an increased proportion of non-fucosylated oligosaccharides in the Fc region compared to a native or parent antibody.
  • the proportion of non-fucosylated oligosaccharides can be at least about 20%, at least about 40%, at least about 60%, at least about 80%, or even about 100% (i.e., no fucosylated oligosaccharides are present).
  • the proportion of non-fucosylated oligosaccharides is preferably at least about 20%, at least about 40%, at least about 60%, at least about 80%, or even about 100% (i.e., no fucosylated oligosaccharides are present).
  • the percentage is the (average) amount of oligosaccharides lacking fucose residues relative to the sum of all oligosaccharides (e.g.
  • Asn297 refers to the asparagine residue located at about position 297 (EU numbering of Fc region residues) in the Fc region; however, Asn297 may also be located about ⁇ 3 amino acids upstream or downstream of position 297, i.e. between positions 294 and 300, due to minor sequence variations in antibodies.
  • Such antibodies with an increased proportion of non-fucosylated oligosaccharides in the Fc region may have improved FcR ⁇ IIIa receptor binding and/or improved effector function, in particular improved ADCC function. See, e.g., US 2003/0157108; US 2004/0093621.
  • Examples of cell lines capable of producing antibodies with reduced fucosylation include Lec13 CHO cells deficient in protein fucosylation (Ripka et al., Arch. Biochem. Biophys. 249: 533-545 (1986); US 2003/0157108; and WO 2004/056312, particularly in Example 11), and knockout cell lines, such as ⁇ -1,6-fucosyltransferase gene FUT8 knockout CHO cells (see, e.g., Yamane-Ohnuk ...)). i et al., Biotech. Bioeng. 87: 614-622 (2004); Kanda, Y. et al., Biotechnol.
  • antibody variants having bisected oligosaccharides are provided, for example, biantennary oligosaccharides attached to the Fc region of the antibody are bisected by GlcNAc.
  • Such antibody variants may have reduced fucosylation and/or improved ADCC function as described above. Examples of such antibody variants are described in, for example, Umana et al., Nat Biotechnol 17, 176-180 (1999); Ferrara et al., Biotechn Bioeng 93, 851-861 (2006); WO 99/54342; WO 2004/065540, WO 2003/011878.
  • Antibody variants having at least one galactose residue in the oligosaccharide attached to the Fc region are also provided. Such antibody variants may have improved CDC function. Such antibody variants are described, for example, in WO 1997/30087; WO 1998/58964; and WO 1999/22764.
  • one or more amino acid modifications can be introduced into the Fc region of an antibody provided herein, thereby generating an Fc region variant.
  • the Fc region variant can be included in a human Fc region sequence (e.g., human IgG1, IgG2, IgG3 or IgG4 Fc region) comprising an amino acid modification (e.g., substitution) at one or more amino acid positions.
  • the present invention encompasses antibody variants that possess some but not all effector functions, making them desirable candidates for applications where the in vivo half-life of the antibody is important, while certain effector functions (such as complement and ADCC) are unnecessary or deleterious.
  • In vitro and/or in vivo cytotoxicity assays can be performed to confirm reduction/ablation of CDC and/or ADCC activity.
  • Fc receptor (FcR) binding assays can be performed to ensure that the antibody lacks Fc ⁇ R binding (and therefore likely lacks ADCC activity), but retains FcRn binding ability.
  • NK cells the main cells that mediate ADCC, express only Fc ⁇ RIII, while monocytes express Fc ⁇ RI, Fc ⁇ RII, and Fc ⁇ RIII.
  • FcR expression on hematopoietic cells is summarized in Table 3 on page 464 of Ravetch and Kinet, Annu. Rev. Immunol. 9: 457-492 (1991).
  • Non-limiting examples of in vitro assays for evaluating ADCC activity of a molecule of interest are described in U.S. Pat. Nos. 5,500,362 (see, e.g., Hellstrom, I. et al., Proc. Nat'l Acad. Sci. USA 83:7059-7063 (1986)) and Hellstrom, I.
  • non-radioactive assays can be used (see, e.g., ACTI TM non-radioactive cytotoxicity assay for flow cytometry (Cell Technology, Inc. Mountain View, CA; and CytoTox Non-radioactive cytotoxicity assays (Promega, Madison, WI).
  • Useful effector cells for such assays include peripheral blood mononuclear cells (PBMCs) and natural killer (NK) cells.
  • ADCC activity of the molecule of interest can be assessed in vivo, for example, in an animal model such as that disclosed in Clynes et al., Proc. Nat'l Acad. Sci. USA 95:652-656 (1998).
  • C1q binding assays can also be performed to confirm that the antibody cannot bind to C1q and therefore lacks CDC activity. See, e.g., C1q and C3c binding ELISAs in WO 2006/029879 and WO 2005/100402.
  • a CDC assay can be performed (see, e.g., Gazzano-Santoro et al., J. Immunol.
  • Antibodies with reduced effector function include those with substitutions of one or more of Fc region residues 238, 265, 269, 270, 297, 327, and 329 (U.S. Pat. No. 6,737,056).
  • Fc mutants include Fc mutants with substitutions at two or more of amino acid positions 265, 269, 270, 297, and 327, including the so-called "DANA" Fc mutant in which residues 265 and 297 are substituted with alanine (U.S. Pat. No. 7,332,581).
  • the antibody variant comprises an Fc region with one or more amino acid substitutions that improve ADCC, such as substitutions at positions 298, 333, and/or 334 of the Fc region (EU numbering of residues).
  • the antibody variant comprises an Fc region with one or more amino acid substitutions that improve FcRn binding, such as substitutions at positions 252, and/or 254, and/or 256 (EU residue numbering) of the Fc region.
  • the antibody variant comprises an Fc region with amino acid substitutions at positions 252, 254, and 256.
  • the substitutions are M252Y, S254T, and T256E in an Fc region derived from a human IgG1 Fc region.
  • the antibody variant comprises an Fc region with amino acid substitutions that reduce Fc ⁇ R binding, such as substitutions at positions 234 and 235 (EU residue numbering) of the Fc region.
  • the substitutions are L234A and L235A (LALA).
  • the antibody variant further comprises D265A and/or P329G in an Fc region derived from a human IgG1 Fc region.
  • the substitutions are L234A, L235A and P329G (LALA-PG) in an Fc region derived from a human IgG1 Fc region (see, e.g., WO 2012/130831A1).
  • the substitutions are L234A, L235A and D265A (LALA-DA) in an Fc region derived from a human IgG1 Fc region.
  • changes are made to the Fc region that result in altered (i.e., improved or reduced) C1q binding and/or complement-dependent cytotoxicity (CDC), as described, for example, in U.S. Pat. No. 6,194,551, WO 99/51642, and Idusogie et al., J. Immunol. 164: 4178-4184 (2000).
  • CDC complement-dependent cytotoxicity
  • Such Fc variants include those having substitutions at one or more of Fc region residues 238, 252, 254, 256, 265, 272, 286, 303, 305, 307, 311, 312, 317, 340, 356, 360, 362, 376, 378, 380, 382, 413, 424 or 434, such as substitution of Fc region residue 434 (see, e.g., U.S. Patent No. 7,371,826; Dall'Acqua, W.F., et al. J. Biol. Chem. 281 (2006) 23514-23524).
  • Fc region residues critical for mouse Fc-mouse FcRn interaction have been identified by site-directed mutagenesis (see, e.g., Dall'Acqua, W.F., et al. J. Immunol 169 (2002) 5171-5180).
  • Residues I253, H310, H433, N434, and H435 (EU numbering according to Kabat) are involved in the interaction (Medesan, C. et al., Eur. J. Immunol. 26 (1996) 2533; Firan, M. et al., Int. Immunol. 13 (2001) 993; Kim, J.K. et al., Eur. J. Immunol. 24 (1994) 542).
  • Residues I253, H310, and H435 were found to be critical for the interaction of human Fc with mouse FcRn (Kim, J.K. et al., Eur. J. Immunol. 29 (1999) 2819).
  • Studies on the human Fc-human FcRn complex showed that residues I253, S254, H435, and Y436 are critical for the interaction (Firan, M. et al., Int. Immunol. 13 (2001) 993; Shields, R.L. et al., J. Biol. Chem. 276 (2001) 6591-6604).
  • the antibody variant comprises an Fc region with one or more amino acid substitutions that reduce FcRn binding, such as substitutions at positions 253, and/or 310, and/or 435 (EU residue numbering) of the Fc region.
  • the antibody variant comprises an Fc region with amino acid substitutions at positions 253, 310, and 435.
  • the substitutions are I253A, H310A, and H435A in an Fc region derived from a human IgG1 Fc region. See, e.g., Grevys, A. et al., J. Immunol. 194 (2015) 5497-5508.
  • the antibody variant comprises an Fc region having one or more amino acid substitutions that reduce FcRn binding, such as substitutions at positions 310, and/or 433, and/or 436 (EU residue numbering) of the Fc region.
  • the antibody variant comprises an Fc region having amino acid substitutions at positions 310, 433, and 436.
  • the substitutions are H310A, H433A, and Y436A in an Fc region derived from a human IgG1 Fc region (see, e.g., WO 2014/177460A1).
  • Antibodies can be produced using recombinant methods and compositions, such as those described in US 4,816,567. For these methods, one or more isolated nucleic acids encoding the antibodies are provided.
  • nucleic acids In the case of natural antibodies or natural antibody fragments, two nucleic acids are required, one for the light chain or its fragment and one for the heavy chain or its fragment.
  • nucleic acid encoding comprises the amino acid sequence of antibody VL and/or comprises the amino acid sequence of VH (e.g., the light and/or heavy chain of the antibody).
  • VL amino acid sequence of antibody
  • VH amino acid sequence of VH
  • nucleic acids can be on the same expression vector or on different expression vectors.
  • nucleic acids are required, one for the first light chain, one for the second light chain comprising a first heteromonomeric Fc region polypeptide, one for the second light chain, and one for the second heavy chain comprising a second heteromonomeric Fc region polypeptide.
  • the four nucleic acids may be contained in one or more nucleic acid molecules or expression vectors.
  • nucleic acids encode an amino acid sequence comprising a first VL of the antibody and/or an amino acid sequence comprising a first VH comprising a first heteromonomeric Fc region and/or an amino acid sequence comprising a second VL and/or an amino acid sequence comprising a second VH comprising a second heteromonomeric Fc region (e.g., the first and/or second light and/or the first and/or second heavy chain of the antibody).
  • These nucleic acids may be on the same expression vector or on different expression vectors, normally, these nucleic acids are located on two or three expression vectors, i.e., one vector may contain more than one of these nucleic acids.
  • bispecific antibodies are CrossMab and T cell bispecific agents (see, e.g., Schaefer, W. et al, PNAS, 108 (2011) 11187-1191).
  • one of the heteromonomer heavy chains contains a so-called “knob mutation” (T366W and optionally one of S354C or Y349C) and the other contains a so-called “hole mutation” (T366S, L368A and Y407V and optionally Y349C or S354C) (see, e.g., Carter, P. et al., Immunotechnol. 2 (1996) 73).
  • an isolated nucleic acid encoding the antibody used in the methods reported herein is provided.
  • one or more vectors comprising such nucleic acids are provided.
  • a host cell comprising such nucleic acid is provided.
  • the host cell comprises (e.g., has been transformed with):
  • a vector comprising a nucleic acid encoding an amino acid sequence comprising an antibody VL and an amino acid sequence comprising an antibody VH, or
  • a first vector and a second vector wherein the first vector comprises a nucleic acid encoding an amino acid sequence comprising antibody VL, and the second vector comprises a nucleic acid encoding an amino acid sequence comprising antibody VH.
  • a first vector comprising a first pair of nucleic acids encoding the following amino acid sequences, one of which comprises a first VL and the other comprises a first VH of an antibody
  • a second vector comprising a second pair of nucleic acids encoding the following amino acid sequences, one of which comprises a second VL and the other comprises a second VH of an antibody
  • first vector comprising a first nucleic acid encoding an amino acid sequence comprising one of the variable domains (preferably a light chain variable domain), a second vector comprising a pair of nucleic acids encoding amino acid sequences, one of which comprises a light chain variable domain and the other comprises a first heavy chain variable domain, and a third vector comprising a pair of nucleic acids encoding amino acid sequences, one of which comprises the other light chain variable domain corresponding to the second vector and the other comprises a second heavy chain variable domain, or
  • a first vector comprising a nucleic acid encoding an amino acid sequence comprising a first VL of an antibody, a second vector comprising a nucleic acid encoding an amino acid sequence comprising a first VH of an antibody, a third vector comprising a nucleic acid encoding an amino acid sequence comprising a second VL of an antibody, and a fourth vector comprising a nucleic acid encoding an amino acid sequence comprising a second VH of an antibody.
  • the host cell is eukaryotic, such as a Chinese hamster ovary (CHO) cell or a lymphoid cell (e.g., a Y0, NS0, Sp20 cell).
  • a method for generating an anti-RSV antibody is provided, wherein the method includes culturing a host cell comprising a nucleic acid encoding an antibody under conditions suitable for expressing the antibody, as provided above, and optionally, recovering the antibody from the host cell (or host cell culture fluid).
  • the nucleic acid (such as described above) encoding the antibody is separated, and inserted into one or more vectors, to further clone and/or express in a host cell.
  • Such nucleic acids can be easily separated and sequenced using conventional procedures (such as by using oligonucleotide probes that can specifically bind to the gene encoding antibody heavy chain and light chain), or generated by a recombinant method or obtained by chemical synthesis.
  • Host cells suitable for cloning or expressing antibody encoding vectors include prokaryotic or eukaryotic cells described herein.
  • antibodies can be produced in bacteria, particularly when glycosylation and Fc effector functions are not required.
  • For expression of antibody fragments and polypeptides in bacteria see, for example, US 5,648,237, US 5,789,199 and US 5,840,523 (also see Charlton, K.A., in Methods in Molecular Biology, Vol. 248, Lo, B.K.C., Humana Press, Totowa, NJ (2003), pp. 245-254, which describes the expression of antibody fragments in Escherichia coli (E. coli.)).
  • the antibody can be separated from the bacterial cell mass in a soluble fraction and can be further purified.
  • eukaryotic microorganisms such as filamentous fungi or yeast are suitable cloning or expression hosts for antibody encoding vectors, including fungi and yeast strains whose glycosylation pathways have been "humanized” to produce antibodies with partially or fully human glycosylation patterns. See Gerngross, T.U., Nat. Biotech. 22 (2004) 1409-1414; Li et al., Nat. Biotech. 24 (2006) 210-215.
  • Suitable host cells for the expression of glycosylated antibodies are also derived from multicellular organisms (invertebrates and vertebrates). Examples of invertebrate cells include plant and insect cells. A number of baculovirus strains have been identified that can be used with insect cells, particularly for transfecting Spodoptera frugiperda cells.
  • Plant cell cultures can also be used as hosts. See, for example, US 5,959,177, US 6,040,498, US 6,420,548, US 7,125,978 and US 6,417,429 (which describe PLANTIBODIES TM technology for producing antibodies in transgenic plants).
  • Vertebrate cells may also be used as hosts.
  • mammalian cell lines adapted to grow in suspension may be useful.
  • Other examples of useful mammalian host cell lines are monkey kidney CV1 line (COS-7) transformed with SV40; human embryonic kidney line (293 or 293 cells, as described, for example, in Graham, F.L. et al., J. Gen Virol. 36 (1977) 59-74); baby hamster kidney cells (BHK); mouse Sertoli cells (TM4 cells, as described, for example, in Mather, J.P., Biol. Reprod.
  • monkey kidney cells CV1; African green monkey kidney cells (VERO-76); human cervical carcinoma cells (HELA); canine kidney cells (MDCK); buffalo rat liver cells (BRL 3A); human lung cells (W138); human hepatocytes (Hep G2); mouse mammary tumor (MMT 060562); TRI cells, as described, for example, in Mather, J.P. et al., Annals N.Y. Acad. Sci. 383 (1982) 44-68; MRC 5 cells; and FS4 cells.
  • Other useful mammalian host cell lines include Chinese hamster ovary (CHO) cells, including DHFR-CHO cells (Urlaub, G. et al., Proc. Natl.
  • myeloma cell lines such as Y0, NS0 and Sp2/0.
  • myeloma cell lines suitable for antibody production see, for example, Yazaki, P. and Wu, A.M., Methods in Molecular Biology, Vol. 248, Lo, B.K.C., ed., Humana Press, Totowa, NJ (2004), pp. 255-268.
  • anti-RSV antibodies provided herein can be identified, screened, or characterized for their physical/chemical properties and/or biological activities by a variety of assays known in the art.
  • the antibodies of the invention are tested for their antigen binding activity, for example, by known methods such as ELISA, Western blot, and the like.
  • competition assays can be used to identify antibodies that compete with a reference anti-RSV antibody for binding to RSV or its antigens.
  • such competing antibodies bind to the same epitope (e.g., a linear or conformational epitope) as the epitope bound by the reference anti-RSV antibody.
  • epitope e.g., a linear or conformational epitope
  • Detailed illustrative methods for locating epitopes bound by antibodies are found in Morris (1996) "Epitope Mapping Protocols", Methods in Molecular Biology vol. 66 (Humana Press, Totowa, NJ).
  • immobilized RSV or its antigen is incubated in a solution comprising a first labeled antibody (which binds RSV or its antigen) (e.g., a reference anti-RSV antibody) and a second unlabeled antibody (which is to be tested for the ability to compete with the first antibody for binding to RSV or its antigen).
  • the second antibody may be present in the hybridoma supernatant.
  • immobilized RSV or its antigen is incubated in a solution comprising the first labeled antibody but not the second unlabeled antibody.
  • an assay for identifying an anti-RSV antibody with biological activity is provided.
  • Biological activity may include, for example, that the anti-RSV antibody inhibits RSV infection of host cells.
  • Antibodies with such biological activity in vivo and/or in vitro are also provided.
  • any anti-RSV antibody provided herein can be used to detect the presence of RSV in a biological sample.
  • the term “detection” encompasses quantitative or qualitative detection.
  • the biological sample comprises a cell or tissue, such as a tumor tissue.
  • the anti-RSV antibody used in the diagnosis or detection method is provided.
  • a method for detecting the presence of RSV in a biological sample is provided.
  • the method includes contacting the biological sample with the anti-RSV antibody under the conditions of allowing the anti-RSV antibody to bind RSV or its antigen, as described herein, and detecting whether a complex is formed between the anti-RSV antibody and RSV or its antigen.Such methods can be in vitro or in vivo methods.
  • anti-RSV antibodies are used to select a subject suitable for treatment with anti-RSV antibodies, for example, wherein the patient is infected with RSV, or suspected of being infected with RSV, or there is a risk of contacting RSV.
  • labeled anti-RSV antibodies include but are not limited to directly detected labels or modules (such as fluorescence, chromogenic, electron-dense, chemiluminescent, and radioactive labels), and modules such as enzymes or ligands indirectly detected via enzyme reactions or molecular interactions.
  • Exemplary labels include, but are not limited to, radioisotopes 32 P, 14 C, 125 I, 3 H, and 131 I, fluorophores such as rare earth chelates or fluorescein and its derivatives, rhodamine and its derivatives, dansyl, umbelliferone, luciferases, such as firefly luciferase and bacterial luciferase (U.S. Pat. No.
  • luciferin 2,3-dihydrophthalazinedione, horseradish peroxidase (HRP), alkaline phosphatase, ⁇ -galactosidase, glucoamylase, lysozyme, carbohydrate oxidases, such as glucose oxidase, galactose oxidase, and glucose-6-phosphate dehydrogenase, heterocyclic oxidases such as uricase and xanthine oxidase (which are coupled to an enzyme such as HRP that oxidizes a dye precursor using hydrogen peroxide), lactoperoxidase, or microperoxidase, biotin/avidin, spin labels, bacteriophage labels, stable free radicals, and the like.
  • HRP horseradish peroxidase
  • compositions of anti-RSV antibodies as described herein are prepared by mixing such antibodies having the desired purity with one or more optional pharmaceutically acceptable carriers (Remington's Pharmaceutical Sciences 16th edition, Osol, A. ed. (1980)) in the form of lyophilized formulations or aqueous solutions.
  • pharmaceutically acceptable carriers are nontoxic to recipients at the doses and concentrations employed, and include, but are not limited to, buffers such as phosphates, citrates, and other organic acids; antioxidants, including ascorbic acid and methionine; preservatives (such as octadecyldimethylbenzyl ammonium chloride; hexamethonium chloride; benzalkonium chloride, benzethonium chloride; phenol, butyl or benzyl alcohol; alkyl parabens, such as methyl or propyl paraben; catechol; resorcinol; cyclohexanol; 3-pentanol; and m-cresol); low molecular weight (less than about 10 residues) polypeptides; proteins, such as serum albumin, gelatin or immunoglobulins; hydrophilic polymers, such as polyvinylpyrrolidone; amino acids, such as glycine, glutamine, asparagine,
  • Exemplary pharmaceutically acceptable carriers herein further comprise an interstitial drug dispersant such as a soluble neutral active hyaluronidase glycoprotein (sHASEGP), for example, human soluble PH-20 hyaluronidase glycoprotein, such as rHuPH20 ( Baxter International, Inc.).
  • sHASEGP soluble neutral active hyaluronidase glycoprotein
  • rHuPH20 Baxter International, Inc.
  • Certain exemplary sHASEGPs and methods of use, including rHuPH20 are described in U.S. Patent Publication Nos. 2005/0260186 and 2006/0104968.
  • sHASEGP is combined with one or more additional glycosaminoglycanases such as chondroitinase.
  • Exemplary lyophilized antibody formulations are described in US Patent No. 6,267,958.
  • Aqueous antibody formulations include those described in US Patent No. 6,171,586 and WO 2006/044908, the latter formulations comprising a histidine-acetate buffer.
  • the formulations herein may also contain more than one active ingredient necessary for the specific indication being treated, preferably those whose activities complement each other and do not adversely affect each other.
  • active ingredients are suitably present in combination in amounts effective for the desired purpose.
  • the active ingredient may be entrapped in microcapsules prepared, for example, by coacervation techniques or by interfacial polymerization (e.g., hydroxymethylcellulose or gelatin microcapsules and poly(methyl methacrylate) microcapsules, respectively), in colloidal drug delivery systems (e.g., liposomes, albumin microspheres, microemulsions, nanoparticles and nanocapsules), or in macroemulsions.
  • colloidal drug delivery systems e.g., liposomes, albumin microspheres, microemulsions, nanoparticles and nanocapsules
  • sustained release preparations can be prepared. Suitable examples of sustained release preparations include semipermeable matrices of solid hydrophobic polymers containing the antibody, which matrices are in the form of shaped articles, e.g. films, or microcapsules.
  • Formulations for in vivo administration are generally sterile. Sterility can be readily accomplished, for example, by filtration through sterile filtration membranes.
  • anti-RSV antibodies Any of the anti-RSV antibodies provided herein can be used in prophylactic or therapeutic methods.
  • an anti-RSV antibody used as a medicine is provided.
  • an anti-RSV antibody used in the prevention or treatment of RSV infection is provided.
  • an anti-RSV antibody used in a prevention or treatment method is provided.
  • the invention provides an anti-RSV antibody used in a method for preventing an individual with a risk of RSV infection, the prevention comprising administering an effective amount of an anti-RSV antibody to an individual.
  • the invention provides an anti-RSV antibody used in a method for treating an individual with RSV infection, the treatment comprising administering an effective amount of an anti-RSV antibody to an individual.
  • the antibody is used to treat RSV infection or delay its progression.
  • the "individual” is preferably a human.
  • the present invention provides the use of an anti-RSV antibody in the manufacture or preparation of a medicament.
  • the medicament is used to treat RSV infection.
  • the medicament is used in a method for treating RSV infection, comprising administering an effective amount of the medicament to an individual with RSV infection.
  • the "individual” can be a human.
  • RSV infection may be, for example, a lower respiratory tract infection.
  • the invention provides a method of treating RSV infection.
  • the method comprises administering an effective amount of an anti-RSV to an individual having cancer.
  • An "individual" according to any of the above embodiments may be a human.
  • the invention provides a pharmaceutical formulation comprising any of the anti-RSV antibodies provided herein, for example for use in any of the above therapeutic methods.
  • the pharmaceutical formulation comprises any of the anti-RSV antibodies provided herein. RSV antibody and a pharmaceutically acceptable carrier.
  • the present invention provides a pharmaceutical formulation comprising any anti-RSV antibody provided herein, for example, used in any of the above therapeutic methods.
  • the pharmaceutical formulation comprises any anti-RSV antibody provided herein and a pharmaceutically acceptable carrier.
  • the pharmaceutical formulation comprises any anti-RSV antibody provided herein and at least one other therapeutic agent.
  • the at least one other therapeutic agent is, for example, another anti-RSV antibody that binds to different epitopes of RSV with the anti-RSV antibody herein.
  • the antibodies of the invention can be used alone or in combination with other agents in therapy.
  • the antibodies of the invention can be co-administered with at least one other therapeutic agent.
  • Such combination therapies noted above encompass co-administration (wherein two or more therapeutic agents are contained in the same or different formulations), and separate administration, in which case administration of the antibodies of the invention may occur before, simultaneously with, and/or after administration of one or more other therapeutic agents.
  • administration of an anti-RSV antibody and administration of another therapeutic agent occur within about one month, or within about one, two or three weeks, or within about one, two, three, four, five, or six days of each other.
  • the antibodies of the invention can be administered by any suitable means, including parenteral, intrapulmonary, and intranasal, and if desired for local treatment, intralesional administration.
  • Parenteral infusions include intramuscular, intravenous, intraarterial, intraperitoneal, or subcutaneous administration.
  • dosing can be by any suitable route, for example by injection, such as intravenous or subcutaneous injection.
  • Various dosing schedules are contemplated herein, including but not limited to single administration or multiple administrations at multiple time points, bolus administration, and pulse infusions.
  • the antibodies of the present invention should be formulated, dosed and administered in a manner consistent with good medical practice. Factors considered in this regard include the specific condition being treated, the specific mammal being treated, the clinical status of the individual patient, the cause of disease, the site of drug delivery, the method of administration, the medication schedule, and other factors known to practicing physicians.
  • the antibody need not but may optionally be formulated with one or more medicaments currently used to prevent or treat the condition.
  • the effective amount of the above-mentioned other medicaments depends on the amount of the antibody present in the formulation, the type of condition or treatment, and other factors discussed above. These medicaments are generally used in the same dosage and route of administration as described herein, or in about 1-99% of the dosage described herein, or in any dosage and by any route, and the dosage and route are determined to be appropriate empirically/clinically.
  • the appropriate dosage of the antibody of the present invention (when used alone or in combination with one or more other therapeutic agents) will depend on the type of disease to be treated, the type of antibody, the severity and course of the disease, the preventive or therapeutic purpose of the antibody administered, previous treatment, the patient's clinical history and response to the antibody, and the discretion of the attending physician.
  • the antibody is suitable for administration to the patient in one or a series of treatments. Depending on the type and severity of the disease, about 1 ⁇ g/kg-15 mg/kg (e.g., 0.1 mg/kg-10 mg/kg) of the antibody can be administered to the patient as a first candidate dose, whether, for example, by one or more separate administrations or by continuous infusion.
  • a typical daily dose may be in the range of about 1 ⁇ g/kg-100 mg/kg or more.
  • An exemplary dosage of the antibody will be in the range of about 0.05 mg/kg to about 10 mg/kg.
  • one or more doses of about 0.5 mg/kg, 2.0 mg/kg, 4.0 mg/kg or 10 mg/kg (or any combination thereof) can be administered to the patient.
  • the above doses can be administered intermittently, such as once a week or every three weeks (such as so that the patient receives about 2 doses to about 20 doses, or, for example, about 6 doses of the antibody).
  • An initial higher loading dose can be administered, followed by one or more lower doses.
  • An exemplary dosing regimen includes administration. However, other dosing regimens may be useful. The progress of the treatment is easily monitored by conventional techniques and assays.
  • an article of manufacture that contains materials useful for treating, preventing and/or diagnosing the conditions described above.
  • the article of manufacture comprises a container and a label or package insert on or associated with the container.
  • Suitable containers include, for example, bottles, vials, syringes, IV solution bags, and the like.
  • the container can be made of a variety of materials such as glass or plastic. Formed.
  • the container holds a composition that is effective for treating, preventing and/or diagnosing a condition, either alone or in combination with another composition, and may have a sterile access port (e.g., the container may be a vial or intravenous solution bag with a stopper pierceable by a hypodermic needle).
  • At least one active agent in the composition is an antibody of the invention.
  • the label or package insert indicates the use of the composition to treat the selected condition.
  • the article of manufacture may comprise: (a) a first container in which the composition is contained, wherein the composition comprises an antibody of the invention; and (b) a second container in which the composition is contained, wherein the composition comprises another therapeutic agent.
  • the article of manufacture in this embodiment of the invention may further comprise a package insert indicating that the composition can be used to treat a specific condition.
  • the article of manufacture may further comprise a second (or third) container comprising a pharmaceutically acceptable buffer, such as bacteriostatic water for injection (BWFI), phosphate-buffered saline, Ringer's solution, and dextrose solution. It may further comprise other materials desirable from a commercial and user standpoint, including other buffers, diluents, filters, needles, and syringes.
  • BWFI bacteriostatic water for injection
  • the present invention provides a group of antibodies, the affinity for RSV A2 pre-F protein is between 0.001nM and 3.25nM, the neutralization activity IC50 for RSV A2 strain is between 0.73ng/mL and 80.04ng/mL, the neutralization activity IC50 for RSV B9320 strain is between 1.11ng/mL and 153.90ng/mL, and the neutralization activity IC50 for RSV B18537 strain is between 0.25 ng/mL to 67.03ng/mL.
  • Peripheral blood was collected from healthy adult volunteers, and the upper plasma and the middle PBMC were obtained by density gradient centrifugation.
  • Memory B cells that specifically bind to the pre-F protein were separated from the PBMC by flow sorting using fluorescently labeled pre-F protein, and transfectable PCR fragments with expression activity were obtained by nested PCR.
  • CHO cells were transfected for expression to obtain cell supernatants containing secreted antibodies. Binding activity screening was performed by ELISA, and hundreds of pre-F binding positive clones were obtained. Multiple recombinant antibodies were tested to have neutralizing activity against RSV A2 strains.
  • amino acid sequences of the antibody CDRs are shown in Table 1.
  • the coding sequences of the light and heavy chain variable regions of the antibodies were cloned into a eukaryotic expression vector carrying the coding sequence of the human IgG1 constant region, transiently transfected into CHO cells for secretory expression, and antibody proteins with a purity of >90% were obtained by protein A affinity purification, namely F6-27, F6-37, F6-38, F6-47, F6-49, F6-56, F6-61, F6-63, F6-65, F6-70, F6-88, F6-115, F6-124, F6-132, F6-133, F6-141, F6-153, F6-172, F6-207, F6-208, F6-210, F6-213, F6-215 and F6-227.
  • Example 2 Characterization of anti-RSV antibodies - Characterization of antigen binding activity by ELISA
  • RSV A2 pre-F protein (Vazyme homemade) diluted to 2 ⁇ g/mL with carbonate buffer at pH 9.6 was added to a 96-well ELISA plate (NEST, 504201) at 100 ⁇ L/well and coated overnight at 4°C. The solution was removed, washed twice with PBST, and blocked with blocking solution (PBS+5% BSA) at 37°C for 2 hours. The solution was removed, and the antibody (starting concentration 5 ⁇ g/mL, 10 gradients in total) diluted 3 times with diluent (PBS+5% BSA) was added to the microplate at 100 ⁇ L/well and incubated at 37°C for 1 hour.
  • the solution was removed, washed 3 times with PBST, and 100 ⁇ L of 1:10000 diluted mouse anti-human IgG Fc-HRP (Vazyme homemade) was added to each well and incubated at 37°C for 1 hour.
  • the solution was removed, washed 3 times with PBST, and 100 ⁇ L of chromogenic substrate TMB was added to each well and incubated at 37°C in the dark for 10 minutes.
  • Table 3.1 and Table 3.2 are the results of different experiments, and the operation of the experiment in Table 3.2 is different only in "using the diluent (PBS + 5% BSA) to dilute the antibody 2 times (starting concentration 1 ⁇ g/mL, a total of 14 gradients)").
  • GraphPad Prism 8.0 was used to plot the antibody concentration and OD value, and the results are shown in Figures 1-1 and 1-2.
  • the affinity fitting curve of the antibody was obtained by Bio-Layer Interferometry (BLI) using the Octet protein analysis system (SARTORIUS, Octet R8).
  • the sensor used HIS1K SARTORIUS, 18-5120
  • the capture agent was 47.6nM RSV A2 pre-F protein
  • the fixation time was 120 seconds
  • the antibody concentrations were 500nM, 167nM, 56nM, 19nM, 6nM, 2nM and 0.69nM
  • the binding time was 60 seconds
  • the dissociation time was 120 seconds
  • the regeneration solution was 10mM glycine-HCl pH 1.5
  • the KD value (M) of the antigen binding affinity of the antibody was calculated using the software Octet Analysis Studio 12.2, and the results are shown in Tables 4.1 and 4.2.
  • the software Octet BLI Discovery 12.2 was used for recording, and the results are shown in Figures 2-1 and 2-2.
  • Example 4 Characterization of anti-RSV antibodies - Characterization of neutralization activity by in vitro microneutralization assay
  • Antibodies serially diluted 3-fold with PBS + 5% HIFBS (starting concentration 0.5 ⁇ g/mL, 7 gradients in total) were added at 60 ⁇ L/well to the virus-containing medium (RSV A2, ATCC VR-1540; RSV B9320, ATCC VR-955; RSV B18537, ATCC VR-1580) (60 ⁇ L/well, 500 pfu) in a 96-well plate (NEST, 701001), and incubate in a cell culture incubator (37°C, 5% CO 2 ) for 1 hour.
  • virus-containing medium RSV A2, ATCC VR-1540; RSV B9320, ATCC VR-955; RSV B18537, ATCC VR-1580
  • CTL fluorescent (enzyme-linked) immunospot analyzer
  • GraphPad Prism 8.0 was used to plot the antibody concentration and neutralization rate, and the results are shown in Figures 3-1 and 3-2. Four-parameter fitting was performed to calculate the IC50 value (ng/mL) of the virus neutralization activity of the antibody, and the results are shown in Tables 5.1 and 5.2.
  • Table 5.2 IC50 values of virus neutralization activity of anti-RSV antibodies (ng/mL)
  • Example 5 Characterization of anti-RSV antibodies - Characterization of epitopes by competition binding
  • RSV A2 pre-F protein was diluted to 10 ⁇ g/mL with buffer (PBS+0.02% Tween 20+0.1% BSA), and the antibody was diluted to 200 nM with the above buffer, and both were added at 200 ⁇ L/well.
  • the above buffer was run on the Octet protein analysis system (SARTORIUS, Octet R8) for 120 seconds to reach the baseline level, the antigen was run until the signal reached 0.3 nm, the above buffer was run for 60 seconds to reach the baseline level, the first antibody was run for 180 seconds, and the second antibody was run for 180 seconds (the same concentration of the first antibody was added to the second antibody to prevent false positive results caused by the dissociation of the first antibody when the second antibody binds when the first antibody is a fast dissociating antibody), and the regeneration solution (10 mM glycine-hydrochloric acid, pH 1.5) and buffer were run alternately for a total of 20 seconds three times. The above cycle was repeated.
  • the regeneration solution (10 mM glycine-hydrochloric acid, pH 1.5
  • the second signal when the first antibody is Ab1 and the second antibody is Ab2+Ab1 is set to H1’2;
  • the second signal when the first antibody is Ab1 and the second antibody is Ab1 is set to H1’1;
  • the second signal when the first antibody is 0 and the second antibody is Ab2 is set to H2;
  • the inhibition rate of the first antibody on the second antibody is: 1-(H1/H2) ⁇ 100%
  • the self-reaction signal is less than 20%; otherwise, the data is invalid.
  • test antibody When a test antibody completely competes with a reference antibody of known epitope, the test antibody is considered to bind to the same epitope as the reference antibody.
  • F6-124, F6-125 and F6-153 compete with MK-1654, ie, these antibodies also recognize the IV epitope of the pre-F protein; F6-133 competes with Motavizumab and MPE8 at the same time, ie, this antibody also recognizes the II and III epitopes of the F protein.

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Abstract

本发明提供一组特异性结合RSV的抗体或其抗原结合片段。本发明还提供编码所述抗体或其抗原结合片段的多核苷酸、包含所述多核苷酸的载体、包含所述载体的宿主细胞、生成所述抗体的方法以及包含所述抗体的组合物。

Description

特异性结合RSV的抗体
相关申请的援引加入
本申请要求2022年12月08日提交的中国发明专利申请CN202211571449.4和2023年01月04日提交的中国发明专利申请CN202310007283.1的优先权，通过援引将其全部内容加入本文中。
技术领域
本发明提供一组特异性结合RSV的抗体或其抗原结合片段。本发明还提供编码所述抗体或其抗原结合片段的多核苷酸、包含所述多核苷酸的载体、包含所述载体的宿主细胞、生成所述抗体的方法以及包含所述抗体的组合物。
背景技术
呼吸道合胞病毒(Respiratory Syncytial Virus，RSV)在5岁以下儿童中造成每年约3300万例急性下呼吸道感染，超过10万例死亡；在65岁以上成年人中造成每年每10万人中约7.2例死亡。另外，RSV感染不能产生永久性免疫，不能保护儿童免于再次感染。RSV已经成为世界范围内引起5岁以下儿童、65岁以上老年人记忆免疫缺陷人群中急性下呼吸道感染的最重要的病原之一，已经成为一种公认的全球卫生问题。
一般病毒性疾病的预防是通过疫苗来进行的，但是RSV自1957年被分离出来，在过去的几十年中没有批准上市的可用于预防的疫苗。之前的疫苗研发出现疫苗不仅没有起到保护作用，反而使得RSV感染引起的肺炎更加严重，导致儿童死亡的情况。可见疫苗研发的成药风险还是非常巨大的。所以，越来越多的关注点都聚焦在RSV抗体药物开发上。目前针对该疾病的唯一预防用药物是1998年首次获得美国FDA批准的Palivizumab单克隆抗体。因此，迫切需要开发新的抗RSV药物，尤其是可治疗RSV感染的药物。
RSV是属于副黏病毒科，肺病毒属的非节段性单股负链RNA病毒。RSV的病毒颗粒含有包膜。病毒颗粒由包膜、核衣壳和核心组成。RSV基因组全长15.2kb，转录10个基因(从3’端到5’端依次为NS1、NS2、N、P、M、SH、G、F、M2和L)，编码11个蛋白。其中，M2含有两个可读框，编码两种蛋白，M2-1和M2-2；其余每种基因编码一种蛋白。NS1和NS2为非结构蛋白；N(核衣壳蛋白)、P(磷酸蛋白)和L(聚合酶亚基蛋白)为核衣壳蛋白；M、M2-1和M2-2为基质蛋白；F(融合蛋白)、G(黏附蛋白)和SH(小疏水蛋白)为跨膜糖蛋白。RSV病毒颗粒表面的G蛋白和F蛋白介导病毒与宿主细胞、病毒感染细胞与未感染细胞之间的吸附和融合，而且是RSV的主要保护性抗原，能诱导机体产生保护性中和抗体。研究结果表明G蛋白在两个亚型间可变性高，诱导机体产生的是型特异性中和抗体，不具有广泛的保护作用。F蛋白是一种高度保守的蛋白，其诱导的保护性抗体为广谱中和抗体，能同时抑制RSVA和B的感染，是潜在的RSV预防及治疗性药物及疫苗研究的有效靶蛋白。F蛋白在被宿主蛋白酶切割成F1(48kDa)和F2(26kDa)两个片段后才具有活性。F蛋白一般会形成F1-F2异二聚体的三聚体结构来行使其融合的功能。在F蛋白上，目前认为能产生中和抗体的表位有6个，即表位I、II、III、IV和V。
发明内容
一方面，本发明提供一种特异性结合RSV的抗体或其抗原结合片段，其包含：
(1)如SEQ ID NO：1所示的CDR-H1，如SEQ ID NO：2所示的CDR-H2，如SEQ ID NO：3所示的CDR-H3，如SEQ ID NO：4所示的CDR-L1，如SEQ ID NO：5所示的CDR-L2，和如SEQ ID NO：6所示的CDR-L3；
(2)如SEQ ID NO：9所示的CDR-H1，如SEQ ID NO：10所示的CDR-H2，如SEQ ID NO：11所示的CDR-H3，如SEQ ID NO：12所示的CDR-L1，如SEQ ID NO：13所示的CDR-L2，和如SEQ ID NO：14所示的CDR-L3；
(3)如SEQ ID NO：17所示的CDR-H1，如SEQ ID NO：18所示的CDR-H2，如SEQ ID NO：19所示的CDR-H3，如SEQ ID NO：20所示的CDR-L1，如SEQ ID NO：21所示的CDR-L2，和如SEQ ID NO：22所示的CDR-L3；
(4)如SEQ ID NO：25所示的CDR-H1，如SEQ ID NO：26所示的CDR-H2，如SEQ ID NO：27所示的CDR-H3，如SEQ ID NO：28所示的CDR-L1，如SEQ ID NO：29所示的CDR-L2，和如SEQ ID NO：30所示的CDR-L3；
(5)如SEQ ID NO：33所示的CDR-H1，如SEQ ID NO：34所示的CDR-H2，如SEQ ID NO：35所示的CDR-H3，如SEQ ID NO：36所示的CDR-L1，如SEQ ID NO：37所示的CDR-L2，和如SEQ ID NO：38所示的CDR-L3；
(6)如SEQ ID NO：41所示的CDR-H1，如SEQ ID NO：42所示的CDR-H2，如SEQ ID NO：43所示的CDR-H3，如SEQ ID NO：44所示的CDR-L1，如SEQ ID NO：45所示的CDR-L2，和如SEQ ID NO：46所示的CDR-L3；
(7)如SEQ ID NO：49所示的CDR-H1，如SEQ ID NO：50所示的CDR-H2，如SEQ ID NO：51所示的CDR-H3，如SEQ ID NO：52所示的CDR-L1，如SEQ ID NO：53所示的CDR-L2，和如SEQ ID NO：54所示的CDR-L3；
(8)如SEQ ID NO：57所示的CDR-H1，如SEQ ID NO：58所示的CDR-H2，如SEQ ID NO：59所示的CDR-H3，如SEQ ID NO：60所示的CDR-L1，如SEQ ID NO：61所示的CDR-L2，和如SEQ ID NO：62所示的CDR-L3；
(9)如SEQ ID NO：65所示的CDR-H1，如SEQ ID NO：66所示的CDR-H2，如SEQ ID NO：67所示的CDR-H3，如SEQ ID NO：68所示的CDR-L1，如SEQ ID NO：69所示的CDR-L2，和如SEQ ID NO：70所示的CDR-L3；
(10)如SEQ ID NO：73所示的CDR-H1，如SEQ ID NO：74所示的CDR-H2，如SEQ ID NO：75所示的CDR-H3，如SEQ ID NO：76所示的CDR-L1，如SEQ ID NO：77所示的CDR-L2，和如SEQ ID NO：78所示的CDR-L3；
(11)如SEQ ID NO：81所示的CDR-H1，如SEQ ID NO：82所示的CDR-H2，如SEQ ID NO：83所示的CDR-H3，如SEQ ID NO：84所示的CDR-L1，如SEQ ID NO：85示的CDR-L2，和如SEQ ID NO：86所示的CDR-L3；
(12)如SEQ ID NO：89所示的CDR-H1，如SEQ ID NO：90所示的CDR-H2，如SEQ ID NO：91所示的CDR-H3，如SEQ ID NO：92所示的CDR-L1，如SEQ ID NO：93所示的CDR-L2，和如SEQ ID NO：94所示的CDR-L3；
(13)如SEQ ID NO：97所示的CDR-H1，如SEQ ID NO：98所示的CDR-H2，如SEQ ID NO：99所示的CDR-H3，如SEQ ID NO：100所示的CDR-L1，如SEQ ID NO：101所示的CDR-L2，和如SEQ ID NO：102所示的CDR-L3；
(14)如SEQ ID NO：105所示的CDR-H1，如SEQ ID NO：106所示的CDR-H2，如SEQ ID NO：107所示的CDR-H3，如SEQ ID NO：108所示的CDR-L1，如SEQ ID NO：109所示的CDR-L2，和如SEQ ID NO：110所示的CDR-L3；
(15)如SEQ ID NO：113所示的CDR-H1，如SEQ ID NO：114所示的CDR-H2，如SEQ ID NO：115所示的CDR-H3，如SEQ ID NO：116所示的CDR-L1，如SEQ ID NO：117所示的CDR-L2，和如SEQ ID NO：118所示的CDR-L3；
(16)如SEQ ID NO：121所示的CDR-H1，如SEQ ID NO：122所示的CDR-H2，如SEQ ID NO：123所示的CDR-H3，如SEQ ID NO：124所示的CDR-L1，如SEQ ID NO：125所示的CDR-L2，和如SEQ ID NO：126所示的CDR-L3；
(17)如SEQ ID NO：129所示的CDR-H1，如SEQ ID NO：130所示的CDR-H2，如SEQ ID NO：131所示的CDR-H3，如SEQ ID NO：132所示的CDR-L1，如SEQ ID NO：133所示的CDR-L2，和如SEQ ID NO：134所示的CDR-L3；
(18)如SEQ ID NO：137所示的CDR-H1，如SEQ ID NO：138所示的CDR-H2，如SEQ ID NO：139所示的CDR-H3，如SEQ ID NO：140所示的CDR-L1，如SEQ ID NO：141所示的CDR-L2，和如SEQ ID NO：142所示的CDR-L3；
(19)如SEQ ID NO：145所示的CDR-H1，如SEQ ID NO：146所示的CDR-H2，如SEQ ID NO：147所示的CDR-H3，如SEQ ID NO：148所示的CDR-L1，如SEQ ID NO：149所示的CDR-L2，和如SEQ ID NO：150所示的CDR-L3；
(20)如SEQ ID NO：153所示的CDR-H1，如SEQ ID NO：154所示的CDR-H2，如SEQ ID NO：155所示的CDR-H3，如SEQ ID NO：156所示的CDR-L1，如SEQ ID NO：157所示的CDR-L2，和如SEQ ID NO：158所示的CDR-L3；
(21)如SEQ ID NO：161所示的CDR-H1，如SEQ ID NO：162所示的CDR-H2，如SEQ ID NO：163所示的CDR-H3，如SEQ ID NO：164所示的CDR-L1，如SEQ ID NO：165所示的CDR-L2，和如SEQ ID NO：166所示的CDR-L3；
(22)如SEQ ID NO：169所示的CDR-H1，如SEQ ID NO：170所示的CDR-H2，如SEQ ID NO：171所示的CDR-H3，如SEQ ID NO：172所示的CDR-L1，如SEQ ID NO：173所示的CDR-L2，和如SEQ ID NO：174所示的CDR-L3；
(23)如SEQ ID NO：177所示的CDR-H1，如SEQ ID NO：178所示的CDR-H2，如SEQ ID NO：179所示的CDR-H3，如SEQ ID NO：180所示的CDR-L1，如SEQ ID NO：181所示的CDR-L2，和如SEQ ID NO：182所示的CDR-L3；或
(24)如SEQ ID NO：185所示的CDR-H1，如SEQ ID NO：186所示的CDR-H2，如SEQ ID NO：187所示的CDR-H3，如SEQ ID NO：188所示的CDR-L1，如SEQ ID NO：189所示的CDR-L2，和如SEQ ID NO：190所示的CDR-L3。
在一个实施方案中，本发明抗体或其抗原结合片段包含：
(1)如SEQ ID NO：7所示的VH和如SEQ ID NO：8所示的VL；
(2)如SEQ ID NO：15所示的VH和如SEQ ID NO：16所示的VL；
(3)如SEQ ID NO：23所示的VH和如SEQ ID NO：24所示的VL；
(4)如SEQ ID NO：31所示的VH和如SEQ ID NO：32所示的VL；
(5)如SEQ ID NO：39所示的VH和如SEQ ID NO：40所示的VL；
(6)如SEQ ID NO：47所示的VH和如SEQ ID NO：48所示的VL；
(7)如SEQ ID NO：55所示的VH和如SEQ ID NO：56所示的VL；
(8)如SEQ ID NO：63所示的VH和如SEQ ID NO：64所示的VL；
(9)如SEQ ID NO：71所示的VH和如SEQ ID NO：72所示的VL；
(10)如SEQ ID NO：79所示的VH和如SEQ ID NO：80所示的VL；
(11)如SEQ ID NO：87所示的VH和如SEQ ID NO：88所示的VL；
(12)如SEQ ID NO：95所示的VH和如SEQ ID NO：96所示的VL；
(13)如SEQ ID NO：103所示的VH和如SEQ ID NO：104所示的VL；
(14)如SEQ ID NO：111所示的VH和如SEQ ID NO：112所示的VL；
(15)如SEQ ID NO：119所示的VH和如SEQ ID NO：120所示的VL；
(16)如SEQ ID NO：127所示的VH和如SEQ ID NO：128所示的VL；
(17)如SEQ ID NO：135所示的VH和如SEQ ID NO：136所示的VL；
(18)如SEQ ID NO：143所示的VH和如SEQ ID NO：144所示的VL；
(19)如SEQ ID NO：151所示的VH和如SEQ ID NO：152所示的VL；
(20)如SEQ ID NO：159所示的VH和如SEQ ID NO：160所示的VL；
(21)如SEQ ID NO：167所示的VH和如SEQ ID NO：168所示的VL；
(22)如SEQ ID NO：175所示的VH和如SEQ ID NO：176所示的VL；
(23)如SEQ ID NO：183所示的VH和如SEQ ID NO：184所示的VL；或
(24)如SEQ ID NO：191所示的VH和如SEQ ID NO：192所示的VL。
在一个实施方案中，本发明抗体或其抗原结合片段包含：
(1)如SEQ ID NO：201所示的重链恒定区，和
(2)如SEQ ID NO：193-200任一所示的轻链恒定区。
在一个实施方案中，本发明抗体或其抗原结合片段包含α重链、δ重链、ε重链、γ重链或μ重链。在一个实施方案中，本发明抗体或其抗原结合片段属于IgG1、IgG2、IgG3或IgG4亚类。在一个实施方案中，本发明抗体或其抗原结合片段包含λ轻链或κ轻链。在一个实施方案中，本发明抗体或其抗原结合片段为全长抗体。在一个实施方案中，本发明抗体或其抗原结合片段为选自Fv、scFv、Fab、Fab′、F(ab′)2和xFab的抗体片段。在一个实施方案中，本发明抗体或其抗原结合片段为嵌合抗体或人抗体或其抗原结合片段。
在一个实施方案中，本发明抗体或其抗原结合片段具有下述一项或多项特性：
(1)能够特异性结合RSV A2 pre-F蛋白；
(2)能够以小于62、61、60、59、50、40、36、35、32、31、30、29、25、24、23、22、21、20、19、18、17、16、15、14、13、12、11、10、9、8、7.5或7.2ng/mL的EC50值，或以比MEDI8897的EC50值小(例如1％至99％，例如至少5％、10％、15％、20％、25％、30％、35％、40％、45％、50％、55％、60％、65％、70％、75％、80％、85％、90％、95％或100％)的EC50值特异性结合RSV A2 pre-F蛋白；
(3)能够以小于3.3、2.2、1.3、1.0、0.9、0.4、0.3、0.2、0.15、0.07、0.06或0.001nM的KD值，或以比MEDI8897的KD值小(例如1％至99％，例如至少5％、10％、15％、20％、25％、30％、35％、40％、45％、50％、55％、60％、65％、70％、75％、80％、85％、90％、95％或100％)的KD值特异性结合RSV A2 pre-F蛋白；
(4)能够抑制RSV(例如A型和/或B型)感染宿主细胞；
(5)能够以小于100、90、80、70、60、50、45、40、35、30、25、20、15、10、9、8、7、6、5、4、3、2或1.5ng/mL的IC50值，或以比MEDI8897的IC50值小(例如1％至99％，例如至少5％、10％、15％、20％、25％、30％、35％、40％、45％、50％、55％、60％、65％、70％、75％、80％、85％、90％、95％或100％)的IC50值抑制RSV A型株(例如A2)感染宿主细胞；
(6)能够以小于160、150、140、130、120、110、100、90、80、70、60、50、40、30、20、15、10、9、8、7、6、5、4或3ng/mL的IC50值，或以比MEDI8897的IC50值小(例如1％至99％，例如至少5％、10％、15％、20％、25％、30％、35％、40％、45％、50％、55％、60％、65％、70％、75％、80％、85％、90％、95％或100％)的IC50值抑制RSV B型株(例如B9320)感染宿主细胞；
(7)能够以小于80、70、60、50、45、40、35、30、20、15、10、9、8、7、6、5、4、3、2或1ng/mL的IC50值，或以比MEDI8897的IC50值小(例如1％至99％，例如至少5％、10％、15％、20％、25％、30％、35％、40％、45％、50％、55％、60％、65％、70％、75％、80％、85％、90％、95％或100％)的IC50值抑制RSV B型株(例如B18537)感染宿主细胞；
(8)能够竞争或抑制MEDI8897对RSV A2 pre-F蛋白的结合；
(9)能够将MEDI8897对RSV A2 pre-F蛋白的结合抑制1％至100％，例如至少5％、10％、15％、20％、25％、30％、35％、40％、45％、50％、55％、60％、65％、70％、75％、80％、81％、82％、83％、84％、85％、86％、87％、88％、89％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％；
(10)能够竞争或抑制MK-1654对RSV A2 pre-F蛋白的结合；
(11)能够将MK-1654对RSV A2 pre-F蛋白的结合抑制1％至100％，例如至少5％、10％、15％、20％、25％、30％、35％、40％、45％、50％、55％、60％、65％、70％、75％、80％、81％、82％、83％、84％、85％、86％、87％、88％、89％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％；
(12)能够竞争或抑制Motavizumab对RSV A2 pre-F蛋白的结合；
(13)能够将Motavizumab对RSV A2 pre-F蛋白的结合抑制1％至100％，例如至少5％、10％、15％、20％、25％、30％、35％、40％、45％、50％、55％、60％、65％、70％、75％、80％、81％、82％、83％、84％、85％、86％、87％、88％、89％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％；
(14)能够竞争或抑制MPE8对RSV A2 pre-F蛋白的结合；
(15)能够将MPE8对RSV A2 pre-F蛋白的结合抑制1％至100％，例如至少5％、10％、15％、20％、25％、30％、35％、40％、45％、50％、55％、60％、65％、70％、75％、80％、81％、82％、83％、84％、85％、86％、87％、88％、89％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％；
(16)能够结合RSV A2 pre-F蛋白的表位；
(17)能够结合RSV A2 pre-F蛋白的IV表位；
(18)能够结合RSV A2 pre-F蛋白的表位和IV表位；
(19)能够结合RSV A2 pre-F蛋白的II表位；
(20)能够结合RSV A2 pre-F蛋白的III表位；和/或
(21)能够结合RSV A2 pre-F蛋白的II表位和III表位。
一方面，本发明提供一种多核苷酸，其编码本发明的抗体或其抗原结合片段。
在一个实施方案中，本发明多核苷酸包含：
(1)SEQ ID NO：202和203；
(2)SEQ ID NO：204和205；
(3)SEQ ID NO：206和207；
(4)SEQ ID NO：208和209；
(5)SEQ ID NO：210和211；
(6)SEQ ID NO：212和213；
(7)SEQ ID NO：214和215；
(8)SEQ ID NO：216和217；
(9)SEQ ID NO：218和219；
(10)SEQ ID NO：220和221；
(11)SEQ ID NO：222和223；
(12)SEQ ID NO：224和225；
(13)SEQ ID NO：226和227；
(14)SEQ ID NO：228和229；
(15)SEQ ID NO：230和231；
(16)SEQ ID NO：232和233；
(17)SEQ ID NO：234和235；
(18)SEQ ID NO：236和237；
(19)SEQ ID NO：238和239；
(20)SEQ ID NO：240和241；
(21)SEQ ID NO：242和243；
(22)SEQ ID NO：244和245；
(23)SEQ ID NO：246和247；或
(24)SEQ ID NO：248和249。
一方面，本发明提供一种载体，其包含本发明的多核苷酸。
一方面，本发明提供一种宿主细胞，其包含本发明的多核苷酸或载体。在一个实施方案中，所述宿主细胞为真核细胞。在一个实施方案中，所述宿主细胞为CHO细胞。
一方面，本发明提供一种生成抗体或其抗原结合片段的方法，其包括：
(a)在适合于表达该抗体或其抗原结合片段的条件下培养本发明的宿主细胞，并
(b)任选地，回收该抗体或其抗原结合片段。
一方面，本发明提供一种组合物，其包含本发明的抗体或其抗原结合片段。
一方面，本发明提供本发明的抗体或其抗原结合片段或组合物，其用作药物。
一方面，本发明提供本发明的抗体或其抗原结合片段或组合物，其用于治疗疾病。在一个实施方案中，该疾病是下呼吸道感染。在一个实施方案中，该疾病是RSV感染导致的疾病。
一方面，本发明提供本发明的抗体或其抗原结合片段或的组合物制造用于治疗疾病的药物的用途。在一个实施方案中，该疾病是下呼吸道感染。
一方面，本发明提供一种治疗个体中的疾病的方法，其包括对该个体施用治疗有效量的本发明的抗体或其抗原结合片段或组合物。在一个实施方案中，该疾病是下呼吸道感染。
附图说明
图1-1、图1-2显示本发明抗体的抗原结合曲线(ELISA)。
图2-1、图2-2显示本发明抗体的抗原结合曲线(BA)。
图3-1、图3-2显示本发明抗体的病毒中和曲线。
图4显示本发明抗体的竞争结合表位测定法示意图。
具体实施方式
出于本文中的目的，“受体人框架”指包含自人免疫球蛋白框架或如下文定义的人共有框架衍生的轻链可变域(VL)框架或重链可变域(VH)框架的氨基酸序列的框架。自人免疫球蛋白框架或人共有框架“衍生”的受体人框架可以包含其相同的氨基酸序列，或者它可以含有氨基酸序列变化。在一些实施方案中，氨基酸变化的数目是10或更少，9或更少，8或更少，7或更少，6或更少，5或更少，4或更少，3或更少，或2或更少。在一些实施方案中，VL受体人框架与VL人免疫球蛋白框架序列或人共有框架序列在序列上相同。
“亲和力”指分子(例如抗体)的单一结合位点与其结合配偶体(例如抗原)之间全部非共价相互作用总和的强度。除非另有指示，如本文中使用的，“结合亲和力”指反映结合对的成员(例如抗体和抗原)之间1∶1相互作用的内在结合亲和力。分子X对其配偶体Y的亲和力通常可以用解离常数(Kd)来表述。亲和力可以通过本领域知道的常用方法来测量，包括本文中所描述的方法。下文描述了用于测量结合亲和力的具体的说明性和例示性的实施方案。
“亲和力成熟的”抗体指在一个或多个高变区(HVR)中具有一处或多处改变的抗体，与不拥有此类改变的亲本抗体相比，此类改变导致该抗体对抗原的亲和力改善。
术语“抗RSV抗体”和“结合RSV的抗体”指能够以足够亲和力结合RSV，使得该抗体可作为诊断剂、预防剂和/或治疗剂用于靶向RSV的抗体。在一个实施方案中，根据例如通过放射免疫测定法(RIA)的测量，抗RSV抗体结合无关的，非RSV的蛋白质的程度小于该抗体对RSV的结合的约10％。在某些实施方案中，结合RSV的抗体具有≤1μM，≤100nM，≤10nM，≤1nM，≤0.1nM，≤0.01nM，或≤0.001nM(例如10-8M或更少，例如10-8M到10-13M，例如10-9M到10-13M)的解离常数(Kd)。在某些实施方案中，“抗RSV抗体”和“结 合RSV的抗体”是“抗RSV pre-F抗体”和“结合RSV pre-F的抗体”，特别是“抗RSV A2 pre-F抗体”和“结合RSV A2 pre-F的抗体”。在某些实施方案中，抗RSV抗体结合在不同RSV毒株中保守的pre-F表位。在一个优选实施方案中，“抗RSV抗体”，“特异性结合RSV的抗体”，和“结合RSV的抗体”指以KD值为1.0 x 10-8mol/l或更低的，在一个实施方案中，KD值为1.0 x 10-9mol/l或更低，在一个实施方案中，KD值为1.0 x 10-9mol/l至1.0 x 10-13mol/l的结合亲和力特异性结合RSV或其抗原或其表位的抗体。在此语境中，结合亲和力是用标准结合测定法，诸如表面等离振子共振技术(GE-Healthcare Uppsala，Sweden；SARTORIUS，R8)测定的，例如使用RSV A2 pre-F蛋白。
本文中的术语“抗体”以最广义使用，并且涵盖各种抗体结构，包括但不限于单克隆抗体，多克隆抗体，多特异性抗体(例如双特异性抗体)，和抗体片段，只要它们展现出期望的抗原结合活性。
“抗体片段”指与完整抗体不同的分子，其包含完整抗体中结合完整抗体结合的抗原的部分。抗体片段的例子包括但不限于Fv，Fab，Fab’，Fab’SH，F(ab’)2，xFab；双抗体；线性抗体；单链抗体分子(例如scFv)；和由抗体片段形成的多特异性抗体。
术语“表位”表示抗原(或是蛋白质性质的或是非蛋白质性质的)上受到抗RSV抗体结合的位点。表位可以自连续氨基酸串(线性表位)形成或包含非连续氨基酸(构象表位)，例如因抗原的折叠(即通过蛋白质性质的抗原的三级折叠)而变成空间接近。线性表位典型地在蛋白质性质的抗原暴露于变性剂之后仍然受到抗RSV抗体结合，而构象表位典型地在用变性剂处理之后遭到破坏。表位包含处于独特空间构象的至少3，至少4，至少5，至少6，至少7，或8-10个氨基酸。
筛选结合特定表位的抗体(即那些结合相同表位的)可以使用本领域例行方法来进行，诸如例如但不限于丙氨酸扫描，肽印迹(见Meth.Mol.Biol.248(2004)443-463)，肽切割分析，表位切除，表位提取，抗原的化学修饰(见Prot.Sci.9(2000)487-496)，和交叉阻断(见“Antibodies，”Harlow and Lane(Cold Spring Harbor Press，Cold Spring Harb.，NY))。
基于抗原结构的抗体概况分析(ASAP)(也称作修饰辅助概况分析(MAP))容许将一群特异性结合RSV的单克隆抗体分仓，其基于来自该群的每一种抗体对化学或酶促修饰的抗原表面的结合概况(见例如US 2004/0101920)。每个仓中的抗体结合相同表位，其可以是与另一个仓所代表的表位截然不同或部分交叠的独特表位。
还可以使用竞争性结合来容易地鉴定抗体是否与参照抗RSV抗体结合相同RSV表位或竞争结合。例如，与参照抗RSV抗体“结合相同表位的抗体”指在竞争测定法中将参照抗RSV抗体对其抗原的结合阻断50％或更多的抗体，且相反，参照抗体在竞争测定法中将该抗体对其抗原的结合阻断50％或更多。还例如，为了测定抗体是否与参照抗RSV抗体结合相同表位，在饱和条件下容许参照抗体结合RSV。在去除过量的参照抗RSV抗体后，评估所讨论的抗RSV抗体结合RSV的能力。如果抗RSV抗体能够在参照抗RSV抗体的饱和结合之后结合RSV，那么可以得出结论，所讨论的抗RSV抗体与参照抗RSV抗体结合不同表位。但是，如果所讨论的抗RSV抗体在参照抗RSV抗体的饱和结合之后不能够结合RSV，那么所讨论的抗RSV抗体可结合与参照抗RSV抗体所结合的表位相同的表位。为了确认所讨论的抗体是否结合相同表位或仅仅受到空间原因阻碍结合，可以使用例行实验(例如肽突变和使用ELISA的，RIA，表面等离振子共振，流式细胞术或本领域可得的任何其它定量或定性抗体结合测定法的结合分析)。这种测定法应当以两种设置进行，即两种抗体均作为饱和抗体。如果在两种设置中，均只有第一(饱和)抗体能够结合RSV，那么可以得出结论，所讨论的抗RSV抗体和参照抗RSV抗体竞争结合RSV。
在一些实施方案中，如果过量1，5，10，20或100倍的一种抗体将另一种的结合抑制至少50％，至少75％，至少90％或甚至99％或更多，如在竞争性结合测定法(见例如Junghans et al.，Cancer Res.50(1990)1495-1502)中测量的，那么认为两种抗体结合相同或交叠表 位。
在一些实施方案中，如果抗原中降低或消除一种抗体的结合的氨基酸突变本质上均也降低或消除另一种的结合，那么认为两种抗体结合相同表位。如果降低或消除一种抗体的结合的氨基酸突变只有一个子集降低或消除另一种的结合，那么认为两种抗体具有“交叠表位”。
术语“嵌合”抗体指其中的重和/或轻链的一部分自特定的来源或物种衍生，而重和/或轻链的剩余部分自不同来源或物种衍生的抗体。
抗体的“类”指其重链拥有的恒定域或恒定区的类型。抗体有5大类：IgA，IgD，IgE，IgG，和IgM，并且这些中的几种可以进一步分成亚类(同种型)，例如IgG1，IgG2，IgG3，IgG4，IgA1，和IgA2。在某些实施方案中，抗体是IgG4同种型的，具有铰链区中的S228P突变以改善IgG4抗体的稳定性。与不同类免疫球蛋白对应的重链恒定域分别称作α，δ，ε，γ，和μ。
在用于本文时，术语“细胞毒剂”指抑制或阻止细胞功能和/或引起细胞死亡或破坏的物质。细胞毒剂包括但不限于：放射性同位素(例如At211，I131，I125，Y90，Re186，Re188，Sm153，Bi212，p32，Pb212和Lu的放射性同位素)；化学治疗剂或药物(例如甲氨蝶呤(methotrexate)，阿霉素(adriamicin)，长春花生物碱类(vinca alkaloids)(长春新碱(vincristine)，长春碱(vinblastine)，依托泊苷(etoposide))，多柔比星(doxorubicin)，美法仑(melphalan)，丝裂霉素(mitomycin)C，苯丁酸氮芥(chlorambucil)，柔红霉素(daunorubicin)或其它嵌入剂)；生长抑制剂；酶及其片段，诸如溶核酶；抗生素；毒素，诸如小分子毒素或者细菌，真菌，植物或动物起源的酶活性毒素，包括其片段和/或变体；和下文公开的各种抗肿瘤或抗癌剂。
“效应器功能”指那些可归于抗体Fc区且随抗体同种型而变化的生物学活性。抗体效应器功能的例子包括：C1q结合和补体依赖性细胞毒性(CDC)；Fc受体结合；抗体依赖性细胞介导的细胞毒性(ADCC)；吞噬作用；细胞表面受体(例如B细胞受体)下调；和B细胞活化。
药剂(例如药学配制剂)的“有效量”指在必需的剂量和时段上有效实现期望的治疗或预防结果的量。
本文中的术语“Fc区”用于定义免疫球蛋白重链中至少含有恒定区一部分的C端区。该术语包括天然序列Fc区和变体Fc区。在一个实施方案中，人IgG重链Fc区自Cys226，或自Pro230延伸至重链的羧基端。然而，Fc区的C端赖氨酸(Lys447)可以存在或不存在。在一个实施方案中，如本文中描述的抗RSV抗体是IgG1同种型的且包含SEQ ID NO：201的恒定重链域。在一个实施方案中，它另外包含C端赖氨酸(Lys447)。在一个实施方案中，如本文中描述的抗RSV抗体是IgG4同种型的。在一个实施方案中，它另外包含C端赖氨酸(Lys447)。除非本文中另有规定，Fc区或恒定区中的氨基酸残基的编号方式依照EU编号***，又称作EU索引，如记载于Kabat et al.，Sequences of Proteins of Immunological Interest，第5版Public Health Service，National Institutes of Health，Bethesda，MD，1991。
“框架”或“FR”指除高变区(HVR)残基外的可变域残基。一般地，可变域的FR由4个FR域组成：FR1，FR2，FR3，和FR4。因而，HVR和FR序列在VH(或VL)中一般以如下的顺序出现：FR1-H1(L1)-FR2-H2(L2)-FR3-H3(L3)-FR4。
术语“全长抗体”，“完整抗体”，和“全抗体”在本文中可互换使用，指与天然抗体结构具有基本上类似的结构或者具有含有如本文中所限定的Fc区的重链的抗体。
术语“宿主细胞”，“宿主细胞系”，和“宿主细胞培养物”可互换使用，并且指已经导入外源核酸的细胞，包括此类细胞的后代。宿主细胞包括“转化体”和“经转化的细胞”，其包括原代的经转化的细胞及自其衍生的后代而不考虑传代的次数。后代在核酸内容物上可以与亲本细胞不完全相同，而是可以含有突变。本文中包括具有与在初始转化细胞中筛选或选择的相同功能或生物学活性的突变体后代。
“人抗体”指拥有与由人或人细胞生成的或利用人抗体全集或其它人抗体编码序列自非人来源衍生的抗体的氨基酸序列对应的氨基酸序列的抗体。人抗体的此定义明确排除包含非人抗原结合残基的人源化抗体。在某些实施方案中，人抗体衍生自非人转基因哺乳动物，例如小鼠，大鼠，或家兔。在某些实施方案中，人抗体衍生自杂交瘤细胞系。
“人共有框架”指代表人免疫球蛋白VL或VH框架序列选集中最常存在的氨基酸残基的框架。通常，人免疫球蛋白VL或VH序列选集来自可变域序列亚组。通常，序列亚组是如Kabat et al.，Sequences of Proteins of Immunological Interest，第5版，NIH Publication91-3242，Bethesda MD(1991)，第1-3卷中的亚组。在一个实施方案中，对于VL，亚组是如Kabat等，见上文中的亚组κI。在一个实施方案中，对于VH，亚组是如Kabat等，见上文中的亚组III。
“人源化”抗体指包含来自非人HVR的氨基酸残基和来自人FR的氨基酸残基的嵌合抗体。在某些实施方案中，人源化抗体会包含至少一个，通常两个基本上整个可变域，其中所有或基本上所有HVR(例如CDR)对应于非人抗体的那些，且所有或基本上所有FR对应于人抗体的那些。任选地，人源化抗体可以至少包含自人抗体衍生的抗体恒定区的一部分。抗体(例如非人抗体)的“人源化形式”指已经经历人源化的抗体。
如本文中使用的，术语“高变区”或“HVR”指抗体可变域中在序列上高变的(“互补决定区”或“CDR”)和/或形成结构上限定的环(“高变环”)和/或含有抗原接触残基(“抗原接触”)的每个区。一般地，抗体包含6个HVR：三个在VH中(H1，H2，H3)，且三个在VL中(L1，L2，L3)。本文中的例示性HVR包括：
(a)高变环，存在于氨基酸残基26-32(L1)，50-52(L2)，91-96(L3)，26-32(H1)，53-55(H2)，和96-101(H3)(Chothia and Lesk，J.Mol.Biol.196：901-917(1987))；
(b)CDR，存在于氨基酸残基24-34(L1)，50-56(L2)，89-97(L3)，31-35b(H1)，50-65(H2)，和95-102(H3)(Kabat et al.，Sequences of Proteins of Immunological Interest，5th Ed.Public Health Service，National Institutes of Health，Bethesda，MD(1991))；
(c)抗原接触，存在于氨基酸残基27c-36(L1)，46-55(L2)，89-96(L3)，30-35b(H1)，47-58(H2)，和93-101(H3)(MacCallum et al.J.Mol.Biol.262：732-745(1996))；和
(d)(a)，(b)，和/或(c)的组合，包括HVR氨基酸残基46-56(L2)，47-56(L2)，48-56(L2)，49-56(L2)，26-35(H1)，26-35b(H1)，49-65(H2)，93-102(H3)，和94-102(H3)。
在一个实施方案中，HVR残基包含下文氨基酸序列的描述中鉴定的那些。
除非另有指示，可变域中的HVR残基和其它残基(例如FR残基)在本文中依照Kabat等，见上文编号。
“免疫缀合物”指与一种或多种异源分子(包括但不限于细胞毒剂)缀合的抗体。
“个体”或“受试者”指哺乳动物。哺乳动物包括但不限于驯养的动物(例如牛，绵羊，猫，犬，和马)，灵长类(例如人和非人灵长类诸如猴)，家兔，和啮齿类(例如小鼠和大鼠)。在某些实施方案中，个体或受试者是人。
“分离的”抗体指已经与其天然环境的组分分开的抗体。在一些实施方案中，抗体纯化至大于95％或99％的纯度，如通过例如电泳(例如SDS-PAGE，等电聚焦(IEF)，毛细管电泳)或层析(例如离子交换或反相HPLC方法)测定的。关于用于评估抗体纯度的方法的综述，见例如Flatman et al.，J.Chromatogr.B 848：79-87(2007)。
“分离的”核酸指已经与其天然环境的组分分开的核酸分子。分离的核酸包括通常含有核酸分子的细胞中含有的核酸分子，但是核酸分子在染色体外或在与其天然染色***置不同的染色***置处存在。
“编码抗RSV抗体的分离的核酸”指编码抗体重和轻链(或其片段)的一种或多种核酸分子，包括单一载体或不同载体中的此类核酸分子，和存在于宿主细胞中的一个或多个位置的此类核酸分子。
在用于本文时，术语“单克隆抗体”指从一群基本上同质的抗体获得的抗体，即构成群体的各个抗体是相同的和/或结合相同表位，除了例如含有天然存在的突变或在单克隆抗体制备物的生成期间发生的可能的变体抗体外，此类变体一般以极小量存在。与通常包含针对不同决定簇(表位)的不同抗体的多克隆抗体制备物不同，单克隆抗体制备物的每个单克隆抗体针对抗原上的单一决定簇。如此，修饰语“单克隆”指示抗体自一群基本上同质的抗体获得的特征，而不应解释为要求通过任何特定方法来生成抗体。例如，可以通过多种技术来生成要依照本发明使用的单克隆抗体，包括但不限于杂交瘤方法，重组DNA方法，噬菌体展示方法，和利用含有所有或部分人免疫球蛋白基因座的转基因动物的方法，本文中描述了用于生成单克隆抗体的此类方法和其它例示性方法。
“裸抗体”指未与异源模块(例如细胞毒性模块)或放射性标记物缀合的抗体。裸抗体可以存在于药学配制剂中。
“天然抗体”指具有不同结构的天然存在的免疫球蛋白分子。例如，天然IgG抗体是约150，000道尔顿的异四聚糖蛋白，由二硫化物键合的两条相同轻链和两条相同重链构成。从N至C端，每条重链具有一个可变区(VH)，又称作可变重域或重链可变域，接着是三个恒定域(CH1，CH2，和CH3)。类似地，从N至C端，每条轻链具有一个可变区(VL)，又称作可变轻域或轻链可变域，接着是一个恒定轻(CL)域。根据其恒定域氨基酸序列，抗体轻链可归入两种类型中的一种，称作卡帕(κ)和拉姆达(λ)。
术语“包装插页”用于指治疗产品的商业包装中通常包含的用法说明书，其含有关于涉及此类治疗产品应用的适应症，用法，剂量，施用，联合疗法，禁忌症和/或警告的信息。
关于参照多肽序列的“百分比(％)氨基酸序列同一性”定义为比对序列并在必要时引入缺口以获取最大百分比序列同一性后，候选序列中与参照多肽序列中的氨基酸残基相同的氨基酸残基的百分率。为测定百分比氨基酸序列同一性目的的对比可以以本领域技术范围内的多种方式进行，例如使用公众可得到的计算机软件，诸如BLAST，BLAST-2，Clustal W，Megalign(DNASTAR)软件或FASTA程序包。本领域技术人员可以决定用于比对序列的合适参数，包括对所比较序列全长获得最大对比所需的任何算法。然而，为了本文中的目的，％氨基酸序列同一性值是使用36.3.8c或更晚的版本FASTA包的ggsearch程序及BLOSUM50比较矩阵生成的。FASTA程序包由W.R.Pearson and D.J.Lipman(1988)“Improved Tools for Biological Sequence Analysis”，PNAS 85：2444-2448；W.R.Pearson(1996)“Effective protein sequence comparison”Meth.Enzymol.266：227-258；和Pearson et al.(1997)Genomics 46：24-36撰写且自http：//fasta.bioch.virginia.edu/fasta_www2/fasta_down.shtml公众可得。或者，可使用在http：//fasta.bioch.virginia.edu/fasta_www2/index.cgi处可及的公共服务器来比较序列，使用ggsearch(全局蛋白质：蛋白质)程序和默认选项(BLOSUM50；打开：-10；延伸：-2；Ktup＝2)以确保实施全局而非局部比对。百分比氨基酸同一性在输出比对标题中给出。
术语“药学配制剂”指处于如下形式的制剂，该形式容许其中含有的活性成分的生物学活性是有效的，且不含对会接受配制剂施用的受试者具有不可接受的毒性的别的组分。
“药学可接受载剂”指药学配制剂中与活性成分不同的，且对受试者无毒的成分。药学可接受载剂包括但不限于缓冲剂，赋形剂，稳定剂，或防腐剂。
在用于本文时，“治疗/处理”(及其语法变型)指试图改变所治疗个体的天然过程的临床干预，并且可以为了预防或者在临床病理学的过程期间实施。治疗的期望效果包括但不限于预防疾病的发生或再发生，减轻症状，减轻/减少疾病的任何直接或间接病理后果，预防转移，降低疾病进展速率，改善或减轻疾病状态，和消退或改善的预后。在一些实施方案中，使用本发明的抗体来延迟疾病的形成或减缓疾病的进展。
本文所用的术语“预防”包括减缓疾病的发作、降低发展疾病的风险、抑制或延缓与 疾病相关的症状的表现或发展、降低随后的收缩的严重性或疾病的发展，改善相关症状，并诱导免疫以预防疾病，
术语“可变区”或“可变域”指抗体重或轻链中牵涉抗体结合抗原的域。天然抗体的重链和轻链可变域(分别为VH和VL)一般具有类似的结构，其中每个域包含4个保守的框架区(FR)和3个高变区(HVR)(见例如Kindt et al.，Kuby Immunology，第6版，W.H.Freeman and Co.，第91页(2007))。单个VH或VL域可以足以赋予抗原结合特异性。此外，可以分别使用来自结合抗原的抗体的VH或VL域筛选互补VL或VH域的文库来分离结合特定抗原的抗体。见例如Portolano et al.，J.Immunol.150：880-887(1993)；Clarkson et al.，Nature352：624-628(1991)。
在用于本文时，术语“载体”指能够增殖与其连接的另一种核酸的核酸分子。该术语包括作为自身复制型核酸结构的载体及并入接受其导入的宿主细胞的基因组中的载体。某些载体能够指导与其可操作连接的核酸的表达。此类载体在本文中称为“表达载体”。
I.组合物和方法
在一个方面，本发明提供分离的结合RSV的抗体。
在某些实施方案中，提供了结合RSV的抗体。本发明的抗体是有用，例如对于诊断或治疗RSV感染，例如下呼吸道感染。
A.例示性抗RSV抗体
在某些实施方案中，提供了一种抗RSV抗体，其中该抗体：
i)结合RSV，特别是RSV pre-F蛋白，更加特别是RSV A2 pre-F蛋白；和/或
ii)抑制RSV，特别是RSV A1、RSV B9320和/或RSV B18537感染宿主细胞，例如Hep2细胞。
在一个方面，本发明提供一种抗RSV抗体，其包含至少一种，两种，三种，四种，五种，或六种选自下述的CDR：(a)包含SEQ ID NO：1的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：2的氨基酸序列的CDR-H2；(c)包含SEQ ID NO：3的氨基酸序列的CDR-H3；(d)包含SEQ ID NO：4的氨基酸序列的CDR-L1；(e)包含SEQ ID NO：5的氨基酸序列的CDR-L2；和(f)包含SEQ ID NO：6的氨基酸序列的CDR-L3。
在一个方面，本发明提供一种抗体，其包含至少一种，至少两种，或所有三种选自下述的VH CDR序列：(a)包含SEQ ID NO：1的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：2的氨基酸序列的CDR-H2；和(c)包含SEQ ID NO：3的氨基酸序列的CDR-H3。在一个实施方案中，该抗体包含包含SEQ ID NO：3的氨基酸序列的CDR-H3。在另一个实施方案中，该抗体包含包含SEQ ID NO：3的氨基酸序列的CDR-H3和包含SEQ ID NO：6的氨基酸序列的CDR-L3。在又一个实施方案中，该抗体包含包含SEQ ID NO：3的氨基酸序列的CDR-H3，包含SEQ ID NO：6的氨基酸序列的CDR-L3，和包含SEQ ID NO：2的氨基酸序列的CDR-H2。在又一个实施方案中，该抗体包含(a)包含SEQ ID NO：1的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：2的氨基酸序列的CDR-H2；和(c)包含SEQ ID NO：3的氨基酸序列的CDR-H3。
在另一个方面，本发明提供一种抗体，其包含至少一种，至少两种，或所有三种选自下述的VL CDR序列：(a)包含SEQ ID NO：4的氨基酸序列的CDR-L1；(b)包含SEQ ID NO：5的氨基酸序列的CDR-L2；和(c)包含SEQ ID NO：6的氨基酸序列的CDR-L3。在一个实施方案中，该抗体包含(a)包含SEQ ID NO：4的氨基酸序列的CDR-L1；(b)包含SEQ ID NO：5的氨基酸序列的CDR-L2；和(c)包含SEQ ID NO：6的氨基酸序列的CDR-L3。
在另一个方面，本发明的抗体包含(a)包含至少一种，至少两种，或所有三种选自下述的VH CDR序列的VH域：(i)包含SEQ ID NO：1的氨基酸序列的CDR-H1，(ii)包含SEQ ID NO：2的氨基酸序列的CDR-H2，和(iii)包含SEQ ID NO：3的氨基酸序列的CDR-H3；和(b)包含至少一种，至少两种，或所有三种选自下述的VL CDR序列的VL域：(i)包含SEQ ID  NO：4的氨基酸序列的CDR-L1，(ii)包含SEQ ID NO：5的氨基酸序列的CDR-L2，和(c)包含SEQ ID NO：6的氨基酸序列的CDR-L3。
在另一个方面，本发明提供一种抗体，其包含(a)包含SEQ ID NO：1的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：2的氨基酸序列的CDR-H2；(c)包含SEQ ID NO：3的氨基酸序列的CDR-H3；(d)包含SEQ ID NO：4的氨基酸序列的CDR-L1；(e)包含SEQ ID NO：5的氨基酸序列的CDR-L2；和(f)包含选自SEQ ID NO：6的氨基酸序列的CDR-L3。
在任何上述实施方案中，抗RSV抗体是人或人源化的。在一个实施方案中，抗RSV抗体包含如任何上述实施方案中的CDR，且进一步包含受体人框架，例如人免疫球蛋白框架或人共有框架。
在另一个方面，抗RSV抗体包含与SEQ ID NO：7的氨基酸序列具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，99％，或100％序列同一性的重链可变域(VH)序列。在某些实施方案中，具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，或99％同一性的VH序列相对于参照序列含有替代(例如保守替代)，***，或删除，但是包含该序列的抗RSV抗体保留结合RSV的能力。在某些实施方案中，在SEQ ID NO：7中替代，***和/或删除总共1至10个氨基酸。在某些实施方案中，替代，***，或删除在CDR以外的区域中(即在FR中)发生。任选地，该抗RSV抗体包含SEQ ID NO：7中的VH序列，包括该序列的翻译后修饰。在一个特定实施方案中，该VH包含一种，两种或三种选自下述的CDR：(a)包含SEQ ID NO：1的氨基酸序列的CDR-H1，(b)包含SEQ ID NO：2的氨基酸序列的CDR-H2，和(c)包含SEQ ID NO：3的氨基酸序列的CDR-H3。
在另一个方面，提供了一种抗RSV抗体，其中该抗体包含与SEQ ID NO：8的氨基酸序列具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，99％，或100％序列同一性的轻链可变域(VL)。在某些实施方案中，具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，或99％同一性的VL序列相对于参照序列含有替代(例如保守替代)，***，或删除，但是包含该序列的抗RSV抗体保留结合RSV的能力。在某些实施方案中，在SEQ ID NO：8中替代，***和/或删除总共1至10个氨基酸。在某些实施方案中，该替代，***，或删除在CDR以外的区域中(即在FR中)发生。任选地，该抗RSV抗体包含SEQ ID NO：8中的VL序列，包括该序列的翻译后修饰。在一个特定实施方案中，该VL包含一种，两种或三种选自下述的CDR：(a)包含SEQ ID NO：4的氨基酸序列的CDR-L1；(b)包含SEQ ID NO：5的氨基酸序列的CDR-L2；和(c)包含SEQ ID NO：6的氨基酸序列的CDR-L3。
在另一个方面，提供了一种抗RSV抗体，其中该抗体包含如任何上文提供的实施方案中的VH，和如任何上文提供的实施方案中的VL。在一个实施方案中，该抗体包含分别在SEQ ID NO：7和SEQ ID NO：8中的VH和VL序列，包括那些序列的翻译后修饰。
在又一个方面，本发明提供与本文中提供的抗RSV抗体结合相同表位的抗体。例如，在某些实施方案中，提供了与包含SEQ ID NO：7的VH序列和SEQ ID NO：8的VL序列的抗RSV抗体结合相同表位的抗体。
在一个方面，本发明提供一种抗RSV抗体，其包含至少一种，两种，三种，四种，五种，或六种选自下述的CDR：(a)包含SEQ ID NO：9的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：10的氨基酸序列的CDR-H2；(c)包含SEQ ID NO：11的氨基酸序列的CDR-H3；(d)包含SEQ ID NO：12的氨基酸序列的CDR-L1；(e)包含SEQ ID NO：13的氨基酸序列的CDR-L2；和(f)包含SEQ ID NO：14的氨基酸序列的CDR-L3。
在一个方面，本发明提供一种抗体，其包含至少一种，至少两种，或所有三种选自下述的VH CDR序列：(a)包含SEQ ID NO：9的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：10的氨基酸序列的CDR-H2；和(c)包含SEQ ID NO：11的氨基酸序列的CDR-H3。在一个实施方案中，该抗体包含包含SEQ ID NO：11的氨基酸序列的CDR-H3。在另一个实施方案中，该抗体包含包含SEQ ID NO：11的氨基酸序列的CDR-H3和包含SEQ ID NO：14的氨基酸 序列的CDR-L3。在又一个实施方案中，该抗体包含包含包含SEQ ID NO：11的氨基酸序列的CDR-H3，包含SEQ ID NO：14的氨基酸序列的CDR-L3，和包含SEQ ID NO：10的氨基酸序列的CDR-H2。在又一个实施方案中，该抗体包含(a)包含SEQ ID NO：9的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：10的氨基酸序列的CDR-H2；和(c)包含SEQ ID NO：11的氨基酸序列的CDR-H3。
在另一个方面，本发明提供一种抗体，其包含至少一种，至少两种，或所有三种选自下述的VL CDR序列：(a)包含SEQ ID NO：12的氨基酸序列的CDR-L1；(b)包含SEQ ID NO：13的氨基酸序列的CDR-L2；和(c)包含SEQ ID NO：14的氨基酸序列的CDR-L3。在一个实施方案中，该抗体包含(a)包含SEQ ID NO：12的氨基酸序列的CDR-L1；(b)包含SEQ ID NO：13的氨基酸序列的CDR-L2；和(c)包含SEQ ID NO：14的氨基酸序列的CDR-L3。
在另一个方面，本发明的抗体包含(a)包含至少一种，至少两种，或所有三种选自下述的VH CDR序列的VH域：(i)包含SEQ ID NO：9的氨基酸序列的CDR-H1，(ii)包含SEQ ID NO：10的氨基酸序列的CDR-H2，和(iii)包含SEQ ID NO：11的氨基酸序列的CDR-H3；和(b)包含至少一种，至少两种，或所有三种选自下述的VL CDR序列的VL域：(i)包含SEQ ID NO：12的氨基酸序列的CDR-L1，(ii)包含SEQ ID NO：13的氨基酸序列的CDR-L2，和(c)包含SEQ ID NO：14的氨基酸序列的CDR-L3。
在另一个方面，本发明提供一种抗体，其包含(a)包含SEQ ID NO：9的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：10的氨基酸序列的CDR-H2；(c)包含SEQ ID NO：11的氨基酸序列的CDR-H3；(d)包含SEQ ID NO：12的氨基酸序列的CDR-L1；(e)包含SEQ ID NO：13的氨基酸序列的CDR-L2；和(f)包含选自SEQ ID NO：14的氨基酸序列的CDR-L3。
在任何上述实施方案中，抗RSV抗体是人或人源化的。在一个实施方案中，抗RSV抗体包含如任何上述实施方案中的CDR，且进一步包含受体人框架，例如人免疫球蛋白框架或人共有框架。
在另一个方面，抗RSV抗体包含与SEQ ID NO：15的氨基酸序列具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，99％，或100％序列同一性的重链可变域(VH)序列。在某些实施方案中，具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，或99％同一性的VH序列相对于参照序列含有替代(例如保守替代)，***，或删除，但是包含该序列的抗RSV抗体保留结合RSV的能力。在某些实施方案中，在SEQ ID NO：15中替代，***和/或删除总共1至10个氨基酸。在某些实施方案中，替代，***，或删除在CDR以外的区域中(即在FR中)发生。任选地，该抗RSV抗体包含SEQ ID NO：15中的VH序列，包括该序列的翻译后修饰。在一个特定实施方案中，该VH包含一种，两种或三种选自下述的CDR：(a)包含SEQ ID NO：9的氨基酸序列的CDR-H1，(b)包含SEQ ID NO：10的氨基酸序列的CDR-H2，和(c)包含SEQ ID NO：11的氨基酸序列的CDR-H3。
在另一个方面，提供了一种抗RSV抗体，其中该抗体包含与SEQ ID NO：16的氨基酸序列具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，99％，或100％序列同一性的轻链可变域(VL)。在某些实施方案中，具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，或99％同一性的VL序列相对于参照序列含有替代(例如保守替代)，***，或删除，但是包含该序列的抗RSV抗体保留结合RSV的能力。在某些实施方案中，在SEQ ID NO：16中替代，***和/或删除总共1至10个氨基酸。在某些实施方案中，该替代，***，或删除在CDR以外的区域中(即在FR中)发生。任选地，该抗RSV抗体包含SEQ ID NO：16中的VL序列，包括该序列的翻译后修饰。在一个特定实施方案中，该VL包含一种，两种或三种选自下述的CDR：(a)包含SEQ ID NO：12的氨基酸序列的CDR-L1；(b)包含SEQ ID NO：13的氨基酸序列的CDR-L2；和(c)包含SEQ ID NO：14的氨基酸序列的CDR-L3。
在另一个方面，提供了一种抗RSV抗体，其中该抗体包含如任何上文提供的实施方案中的VH，和如任何上文提供的实施方案中的VL。在一个实施方案中，该抗体包含分别 在SEQ ID NO：15和SEQ ID NO：16中的VH和VL序列，包括那些序列的翻译后修饰。
在又一个方面，本发明提供与本文中提供的抗RSV抗体结合相同表位的抗体。例如，在某些实施方案中，提供了与包含SEQ ID NO：15的VH序列和SEQ ID NO：16的VL序列的抗RSV抗体结合相同表位的抗体。
在一个方面，本发明提供一种抗RSV抗体，其包含至少一种，两种，三种，四种，五种，或六种选自下述的CDR：(a)包含SEQ ID NO：17的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：18的氨基酸序列的CDR-H2；(c)包含SEQ ID NO：19的氨基酸序列的CDR-H3；(d)包含SEQ ID NO：20的氨基酸序列的CDR-L1；(e)包含SEQ ID NO：21的氨基酸序列的CDR-L2；和(f)包含SEQ ID NO：22的氨基酸序列的CDR-L3。
在一个方面，本发明提供一种抗体，其包含至少一种，至少两种，或所有三种选自下述的VH CDR序列：(a)包含SEQ ID NO：17的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：18的氨基酸序列的CDR-H2；和(c)包含SEQ ID NO：19的氨基酸序列的CDR-H3。在一个实施方案中，该抗体包含包含SEQ ID NO：19的氨基酸序列的CDR-H3。在另一个实施方案中，该抗体包含包含SEQ ID NO：19的氨基酸序列的CDR-H3和包含SEQ ID NO：22的氨基酸序列的CDR-L3。在又一个实施方案中，该抗体包含包含SEQ ID NO：19的氨基酸序列的CDR-H3，包含SEQ ID NO：22的氨基酸序列的CDR-L3，和包含SEQ ID NO：18的氨基酸序列的CDR-H2。在又一个实施方案中，该抗体包含(a)包含SEQ ID NO：17的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：18的氨基酸序列的CDR-H2；和(c)包含SEQ ID NO：19的氨基酸序列的CDR-H3。
在另一个方面，本发明提供一种抗体，其包含至少一种，至少两种，或所有三种选自下述的VL CDR序列：(a)包含SEQ ID NO：20的氨基酸序列的CDR-L1；(b)包含SEQ ID NO：21的氨基酸序列的CDR-L2；和(c)包含SEQ ID NO：22的氨基酸序列的CDR-L3。在一个实施方案中，该抗体包含(a)包含SEQ ID NO：20的氨基酸序列的CDR-L1；(b)包含SEQ ID NO：21的氨基酸序列的CDR-L2；和(c)包含SEQ ID NO：22的氨基酸序列的CDR-L3。
在另一个方面，本发明的抗体包含(a)包含至少一种，至少两种，或所有三种选自下述的VH CDR序列的VH域：(i)包含SEQ ID NO：17的氨基酸序列的CDR-H1，(ii)包含SEQ ID NO：18的氨基酸序列的CDR-H2，和(iii)包含SEQ ID NO：19的氨基酸序列的CDR-H3；和(b)包含至少一种，至少两种，或所有三种选自下述的VL CDR序列的VL域：(i)包含SEQ ID NO：20的氨基酸序列的CDR-L1，(ii)包含SEQ ID NO：21的氨基酸序列的CDR-L2，和(c)包含SEQ ID NO：22的氨基酸序列的CDR-L3。
在另一个方面，本发明提供一种抗体，其包含(a)包含SEQ ID NO：17的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：18的氨基酸序列的CDR-H2；(c)包含SEQ ID NO：19的氨基酸序列的CDR-H3；(d)包含SEQ ID NO：20的氨基酸序列的CDR-L1；(e)包含SEQ ID NO：21的氨基酸序列的CDR-L2；和(f)包含选自SEQ ID NO：22的氨基酸序列的CDR-L3。
在任何上述实施方案中，抗RSV抗体是人或人源化的。在一个实施方案中，抗RSV抗体包含如任何上述实施方案中的CDR，且进一步包含受体人框架，例如人免疫球蛋白框架或人共有框架。
在另一个方面，抗RSV抗体包含与SEQ ID NO：23的氨基酸序列具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，99％，或100％序列同一性的重链可变域(VH)序列。在某些实施方案中，具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，或99％同一性的VH序列相对于参照序列含有替代(例如保守替代)，***，或删除，但是包含该序列的抗RSV抗体保留结合RSV的能力。在某些实施方案中，在SEQ ID NO：23中替代，***和/或删除总共1至10个氨基酸。在某些实施方案中，替代，***，或删除在CDR以外的区域中(即在FR中)发生。任选地，该抗RSV抗体包含SEQ ID NO：23中的VH序列，包括该序列的翻译后修饰。在一个特定实施方案中，该VH包含一种，两种或三种选自下述的 CDR：(a)包含SEQ ID NO：17的氨基酸序列的CDR-H1，(b)包含SEQ ID NO：18的氨基酸序列的CDR-H2，和(c)包含SEQ ID NO：19的氨基酸序列的CDR-H3。
在另一个方面，提供了一种抗RSV抗体，其中该抗体包含与SEQ ID NO：24的氨基酸序列具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，99％，或100％序列同一性的轻链可变域(VL)。在某些实施方案中，具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，或99％同一性的VL序列相对于参照序列含有替代(例如保守替代)，***，或删除，但是包含该序列的抗RSV抗体保留结合RSV的能力。在某些实施方案中，在SEQ ID NO：24中替代，***和/或删除总共1至10个氨基酸。在某些实施方案中，该替代，***，或删除在CDR以外的区域中(即在FR中)发生。任选地，该抗RSV抗体包含SEQ ID NO：24中的VL序列，包括该序列的翻译后修饰。在一个特定实施方案中，该VL包含一种，两种或三种选自下述的CDR：(a)包含SEQ ID NO：20的氨基酸序列的CDR-L1；(b)包含SEQ ID NO：21的氨基酸序列的CDR-L2；和(c)包含SEQ ID NO：22的氨基酸序列的CDR-L3。
在另一个方面，提供了一种抗RSV抗体，其中该抗体包含如任何上文提供的实施方案中的VH，和如任何上文提供的实施方案中的VL。在一个实施方案中，该抗体包含分别在SEQ ID NO：23和SEQ ID NO：24中的VH和VL序列，包括那些序列的翻译后修饰。
在又一个方面，本发明提供与本文中提供的抗RSV抗体结合相同表位的抗体。例如，在某些实施方案中，提供了与包含SEQ ID NO：23的VH序列和SEQ ID NO：24的VL序列的抗RSV抗体结合相同表位的抗体。
在一个方面，本发明提供一种抗RSV抗体，其包含至少一种，两种，三种，四种，五种，或六种选自下述的CDR：(a)包含SEQ ID NO：25的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：26的氨基酸序列的CDR-H2；(c)包含SEQ ID NQ：27的氨基酸序列的CDR-H3；(d)包含SEQ ID NO：28的氨基酸序列的CDR-L1；(e)包含SEQ ID NO：29的氨基酸序列的CDR-L2；和(f)包含SEQ ID NO：30的氨基酸序列的CDR-L3。
在一个方面，本发明提供一种抗体，其包含至少一种，至少两种，或所有三种选自下述的VH CDR序列：(a)包含SEQ ID NO：25的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：26的氨基酸序列的CDR-H2；和(c)包含SEQ ID NO：27的氨基酸序列的CDR-H3。在一个实施方案中，该抗体包含包含SEQ ID NO：27的氨基酸序列的CDR-H3。在另一个实施方案中，该抗体包含包含SEQ ID NO：27的氨基酸序列的CDR-H3和包含SEQ ID NO：30的氨基酸序列的CDR-L3。在又一个实施方案中，该抗体包含包含SEQ ID NO：27的氨基酸序列的CDR-H3，包含SEQ ID NO：30的氨基酸序列的CDR-L3，和包含SEQ ID NO：26的氨基酸序列的CDR-H2。在又一个实施方案中，该抗体包含(a)包含SEQ ID NO：25的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：26的氨基酸序列的CDR-H2；和(c)包含SEQ ID NO：27的氨基酸序列的CDR-H3。
在另一个方面，本发明提供一种抗体，其包含至少一种，至少两种，或所有三种选自下述的VL CDR序列：(a)包含SEQ ID NO：28的氨基酸序列的CDR-L1；(b)包含SEQ ID NO：29的氨基酸序列的CDR-L2；和(c)包含SEQ ID NO：30的氨基酸序列的CDR-L3。在一个实施方案中，该抗体包含(a)包含SEQ ID NO：28的氨基酸序列的CDR-L1；(b)包含SEQ ID NO：29的氨基酸序列的CDR-L2；和(c)包含SEQ ID NO：30的氨基酸序列的CDR-L3。
在另一个方面，本发明的抗体包含(a)包含至少一种，至少两种，或所有三种选自下述的VH CDR序列的VH域：(i)包含SEQ ID NO：25的氨基酸序列的CDR-H1，(ii)包含SEQ ID NO：26的氨基酸序列的CDR-H2，和(iii)包含SEQ ID NO：27的氨基酸序列的CDR-H3；和(b)包含至少一种，至少两种，或所有三种选自下述的VL CDR序列的VL域：(i)包含SEQ ID NO：28的氨基酸序列的CDR-L1，(ii)包含SEQ ID NO：29的氨基酸序列的CDR-L2，和(c)包含SEQ ID NO：30的氨基酸序列的CDR-L3。
在另一个方面，本发明提供一种抗体，其包含(a)包含SEQ ID NO：25的氨基酸序列的 CDR-H1；(b)包含SEQ ID NO：26的氨基酸序列的CDR-H2；(c)包含SEQ ID NO：27的氨基酸序列的CDR-H3；(d)包含SEQ ID NO：28的氨基酸序列的CDR-L1；(e)包含SEQ ID NO：29的氨基酸序列的CDR-L2；和(f)包含选自SEQ ID NO：30的氨基酸序列的CDR-L3。
在任何上述实施方案中，抗RSV抗体是人或人源化的。在一个实施方案中，抗RSV抗体包含如任何上述实施方案中的CDR，且进一步包含受体人框架，例如人免疫球蛋白框架或人共有框架。
在另一个方面，抗RSV抗体包含与SEQ ID NO：31的氨基酸序列具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，99％，或100％序列同一性的重链可变域(VH)序列。在某些实施方案中，具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，或99％同一性的VH序列相对于参照序列含有替代(例如保守替代)，***，或删除，但是包含该序列的抗RSV抗体保留结合RSV的能力。在某些实施方案中，在SEQ ID NO：31中替代，***和/或删除总共1至10个氨基酸。在某些实施方案中，替代，***，或删除在CDR以外的区域中(即在FR中)发生。任选地，该抗RSV抗体包含SEQ ID NO：31中的VH序列，包括该序列的翻译后修饰。在一个特定实施方案中，该VH包含一种，两种或三种选自下述的CDR：(a)包含SEQ ID NO：25的氨基酸序列的CDR-H1，(b)包含SEQ ID NO：26的氨基酸序列的CDR-H2，和(c)包含SEQ ID NO：27的氨基酸序列的CDR-H3。
在另一个方面，提供了一种抗RSV抗体，其中该抗体包含与SEQ ID NO：32的氨基酸序列具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，99％，或100％序列同一性的轻链可变域(VL)。在某些实施方案中，具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，或99％同一性的VL序列相对于参照序列含有替代(例如保守替代)，***，或删除，但是包含该序列的抗RSV抗体保留结合RSV的能力。在某些实施方案中，在SEQ ID NO：32中替代，***和/或删除总共1至10个氨基酸。在某些实施方案中，该替代，***，或删除在CDR以外的区域中(即在FR中)发生。任选地，该抗RSV抗体包含SEQ ID NO：32中的VL序列，包括该序列的翻译后修饰。在一个特定实施方案中，该VL包含一种，两种或三种选自下述的CDR：(a)包含SEQ ID NO：28的氨基酸序列的CDR-L1；(b)包含SEQ ID NO：29的氨基酸序列的CDR-L2；和(c)包含SEQ ID NO：30的氨基酸序列的CDR-L3。
在另一个方面，提供了一种抗RSV抗体，其中该抗体包含如任何上文提供的实施方案中的VH，和如任何上文提供的实施方案中的VL。在一个实施方案中，该抗体包含分别在SEQ ID NO：31和SEQ ID NO：32中的VH和VL序列，包括那些序列的翻译后修饰。
在又一个方面，本发明提供与本文中提供的抗RSV抗体结合相同表位的抗体。例如，在某些实施方案中，提供了与包含SEQ ID NO：31的VH序列和SEQ ID NO：32的VL序列的抗RSV抗体结合相同表位的抗体。
在一个方面，本发明提供一种抗RSV抗体，其包含至少一种，两种，三种，四种，五种，或六种选自下述的CDR：(a)包含SEQ ID NO：33的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：34的氨基酸序列的CDR-H2；(c)包含SEQ ID NO：35的氨基酸序列的CDR-H3；(d)包含SEQ ID NO：36的氨基酸序列的CDR-L1；(e)包含SEQ ID NO：37的氨基酸序列的CDR-L2；和(f)包含SEQ ID NO：38的氨基酸序列的CDR-L3。
在一个方面，本发明提供一种抗体，其包含至少一种，至少两种，或所有三种选自下述的VH CDR序列：(a)包含SEQ ID NO：33的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：34的氨基酸序列的CDR-H2；和(c)包含SEQ ID NO：35的氨基酸序列的CDR-H3。在一个实施方案中，该抗体包含包含SEQ ID NO：35的氨基酸序列的CDR-H3。在另一个实施方案中，该抗体包含包含SEQ ID NO：35的氨基酸序列的CDR-H3和包含SEQ ID NO：38的氨基酸序列的CDR-L3。在又一个实施方案中，该抗体包含包含SEQ ID NO：35的氨基酸序列的CDR-H3，包含SEQ ID NO：38的氨基酸序列的CDR-L3，和包含SEQ ID NO：34的氨基酸序列的CDR-H2。在又一个实施方案中，该抗体包含(a)包含SEQ ID NO：33的氨基酸序列 的CDR-H1；(b)包含SEQ ID NO：34的氨基酸序列的CDR-H2；和(c)包含SEQ ID NO：35的氨基酸序列的CDR-H3。
在另一个方面，本发明提供一种抗体，其包含至少一种，至少两种，或所有三种选自下述的VL CDR序列：(a)包含SEQ ID NO：36的氨基酸序列的CDR-L1；(b)包含SEQ ID NO：37的氨基酸序列的CDR-L2；和(c)包含SEQ ID NO：38的氨基酸序列的CDR-L3。在一个实施方案中，该抗体包含(a)包含SEQ ID NO：36的氨基酸序列的CDR-L1；(b)包含SEQ ID NO：37的氨基酸序列的CDR-L2；和(c)包含SEQ ID NO：38的氨基酸序列的CDR-L3。
在另一个方面，本发明的抗体包含(a)包含至少一种，至少两种，或所有三种选自下述的VH CDR序列的VH域：(i)包含SEQ ID NO：33的氨基酸序列的CDR-H1，(ii)包含SEQ ID NO：34的氨基酸序列的CDR-H2，和(iii)包含选自SEQ ID NO：35的氨基酸序列的CDR-H3；和(b)包含至少一种，至少两种，或所有三种选自下述的VL CDR序列的VL域：(i)包含SEQ ID NO：36的氨基酸序列的CDR-L1，(ii)包含SEQ ID NO：37的氨基酸序列的CDR-L2，和(c)包含SEQ ID NO：38的氨基酸序列的CDR-L3。
在另一个方面，本发明提供一种抗体，其包含(a)包含SEQ ID NO：33的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：34的氨基酸序列的CDR-H2；(c)包含SEQ ID NO：35的氨基酸序列的CDR-H3；(d)包含SEQ ID NO：36的氨基酸序列的CDR-L1；(e)包含SEQ ID NO：37的氨基酸序列的CDR-L2；和(f)包含选自SEQ ID NO：38的氨基酸序列的CDR-L3。
在任何上述实施方案中，抗RSV抗体是人或人源化的。在一个实施方案中，抗RSV抗体包含如任何上述实施方案中的CDR，且进一步包含受体人框架，例如人免疫球蛋白框架或人共有框架。
在另一个方面，抗RSV抗体包含与SEQ ID NO：39的氨基酸序列具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，99％，或100％序列同一性的重链可变域(VH)序列。在某些实施方案中，具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，或99％同一性的VH序列相对于参照序列含有替代(例如保守替代)，***，或删除，但是包含该序列的抗RSV抗体保留结合RSV的能力。在某些实施方案中，在SEQ ID NO：39中替代，***和/或删除总共1至10个氨基酸。在某些实施方案中，替代，***，或删除在CDR以外的区域中(即在FR中)发生。任选地，该抗RSV抗体包含SEQ ID NO：39中的VH序列，包括该序列的翻译后修饰。在一个特定实施方案中，该VH包含一种，两种或三种选自下述的CDR：(a)包含SEQ ID NO：33的氨基酸序列的CDR-H1，(b)包含SEQ ID NO：34的氨基酸序列的CDR-H2，和(c)包含SEQ ID NO：35的氨基酸序列的CDR-H3。
在另一个方面，提供了一种抗RSV抗体，其中该抗体包含与SEQ ID NO：40的氨基酸序列具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，99％，或100％序列同一性的轻链可变域(VL)。在某些实施方案中，具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，或99％同一性的VL序列相对于参照序列含有替代(例如保守替代)，***，或删除，但是包含该序列的抗RSV抗体保留结合RSV的能力。在某些实施方案中，在SEQ ID NO：40中替代，***和/或删除总共1至10个氨基酸。在某些实施方案中，该替代，***，或删除在CDR以外的区域中(即在FR中)发生。任选地，该抗RSV抗体包含SEQ ID NO：40中的VL序列，包括该序列的翻译后修饰。在一个特定实施方案中，该VL包含一种，两种或三种选自下述的CDR：(a)包含SEQ ID NO：36的氨基酸序列的CDR-L1；(b)包含SEQ ID NO：37的氨基酸序列的CDR-L2；和(c)包含SEQ ID NO：38的氨基酸序列的CDR-L3。
在另一个方面，提供了一种抗RSV抗体，其中该抗体包含如任何上文提供的实施方案中的VH，和如任何上文提供的实施方案中的VL。在一个实施方案中，该抗体包含分别在SEQ ID NO：39和SEQ ID NO：40中的VH和VL序列，包括那些序列的翻译后修饰。
在又一个方面，本发明提供与本文中提供的抗RSV抗体结合相同表位的抗体。例如，在某些实施方案中，提供了与包含SEQ ID NO：39的VH序列和SEQ ID NO：40的VL序列 的抗RSV抗体结合相同表位的抗体。
在一个方面，本发明提供一种抗RSV抗体，其包含至少一种，两种，三种，四种，五种，或六种选自下述的CDR：(a)包含SEQ ID NO：41的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：42的氨基酸序列的CDR-H2；(c)包含SEQ ID NO：43的氨基酸序列的CDR-H3；(d)包含SEQ ID NO：44的氨基酸序列的CDR-L1；(e)包含SEQ ID NO：45的氨基酸序列的CDR-L2；和(f)包含SEQ ID NO：46的氨基酸序列的CDR-L3。
在一个方面，本发明提供一种抗体，其包含至少一种，至少两种，或所有三种选自下述的VH CDR序列：(a)包含SEQ ID NO：41的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：42的氨基酸序列的CDR-H2；和(c)包含SEQ ID NO：43的氨基酸序列的CDR-H3。在一个实施方案中，该抗体包含包含SEQ ID NO：43的氨基酸序列的CDR-H3。在另一个实施方案中，该抗体包含包含SEQ ID NO：43的氨基酸序列的CDR-H3和包含SEQ ID NO：46的氨基酸序列的CDR-L3。在又一个实施方案中，该抗体包含包含SEQ ID NO：43的氨基酸序列的CDR-H3，包含SEQ ID NO：46的氨基酸序列的CDR-L3，和包含SEQ ID NO：42的氨基酸序列的CDR-H2。在又一个实施方案中，该抗体包含(a)包含SEQ ID NO：41的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：42的氨基酸序列的CDR-H2；和(c)包含SEQ ID NO：43的氨基酸序列的CDR-H3。
在另一个方面，本发明提供一种抗体，其包含至少一种，至少两种，或所有三种选自下述的VL CDR序列：(a)包含SEQ ID NO：44的氨基酸序列的CDR-L1；(b)包含SEQ ID NO：45的氨基酸序列的CDR-L2；和(c)包含SEQ ID NO：46的氨基酸序列的CDR-L3。在一个实施方案中，该抗体包含(a)包含SEQ ID NO：44的氨基酸序列d CDR-L1；(b)包含SEQ ID NO：45的氨基酸序列的CDR-L2；和(c)包含SEQ ID NO：46的氨基酸序列的CDR-L3。
在另一个方面，本发明的抗体包含(a)包含至少一种，至少两种，或所有三种选自下述的VH CDR序列的VH域：(i)包含SEQ ID NO：41的氨基酸序列的CDR-H1，(ii)包含SEQ ID NO：42的氨基酸序列的CDR-H2，和(iii)包含SEQ ID NO：43的氨基酸序列的CDR-H3；和(b)包含至少一种，至少两种，或所有三种选自下述的VL CDR序列的VL域：(i)包含SEQ ID NO：44的氨基酸序列的CDR-L1，(ii)包含SEQ ID NO：45的氨基酸序列的CDR-L2，和(c)包含SEQ ID NO：46的氨基酸序列的CDR-L3。
在另一个方面，本发明提供一种抗体，其包含(a)包含SEQ ID NO：41的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：42的氨基酸序列的CDR-H2；(c)包含SEQ ID NO：43的氨基酸序列的CDR-H3；(d)包含SEQ ID NO：44的氨基酸序列的CDR-L1；(e)包含SEQ ID NO：45的氨基酸序列的CDR-L2；和(f)包含选自SEQ ID NO：46的氨基酸序列的CDR-L3。
在任何上述实施方案中，抗RSV抗体是人或人源化的。在一个实施方案中，抗RSV抗体包含如任何上述实施方案中的CDR，且进一步包含受体人框架，例如人免疫球蛋白框架或人共有框架。
在另一个方面，抗RSV抗体包含与SEQ ID NO：47的氨基酸序列具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，99％，或100％序列同一性的重链可变域(VH)序列。在某些实施方案中，具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，或99％同一性的VH序列相对于参照序列含有替代(例如保守替代)，***，或删除，但是包含该序列的抗RSV抗体保留结合RSV的能力。在某些实施方案中，在SEQ ID NO：47中替代，***和/或删除总共1至10个氨基酸。在某些实施方案中，替代，***，或删除在CDR以外的区域中(即在FR中)发生。任选地，该抗RSV抗体包含SEQ ID NO：47中的VH序列，包括该序列的翻译后修饰。在一个特定实施方案中，该VH包含一种，两种或三种选自下述的CDR：(a)包含SEQ ID NO：41的氨基酸序列的CDR-H1，(b)包含SEQ ID NO：42的氨基酸序列的CDR-H2，和(c)包含SEQ ID NO：43的氨基酸序列的CDR-H3。
在另一个方面，提供了一种抗RSV抗体，其中该抗体包含与SEQ ID NO：48的氨基酸 序列具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，99％，或100％序列同一性的轻链可变域(VL)。在某些实施方案中，具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，或99％同一性的VL序列相对于参照序列含有替代(例如保守替代)，***，或删除，但是包含该序列的抗RSV抗体保留结合RSV的能力。在某些实施方案中，在SEQ ID NO：48中替代，***和/或删除总共1至10个氨基酸。在某些实施方案中，该替代，***，或删除在CDR以外的区域中(即在FR中)发生。任选地，该抗RSV抗体包含SEQ ID NO：48中的VL序列，包括该序列的翻译后修饰。在一个特定实施方案中，该VL包含一种，两种或三种选自下述的CDR：(a)包含SEQ ID NO：44的氨基酸序列的CDR-L1；(b)包含SEQ ID NO：45的氨基酸序列的CDR-L2；和(c)包含SEQ ID NO：46的氨基酸序列的CDR-L3。
在另一个方面，提供了一种抗RSV抗体，其中该抗体包含如任何上文提供的实施方案中的VH，和如任何上文提供的实施方案中的VL。在一个实施方案中，该抗体包含分别在SEQ ID NO：47和SEQ ID NO：48中的VH和VL序列，包括那些序列的翻译后修饰。
在又一个方面，本发明提供与本文中提供的抗RSV抗体结合相同表位的抗体。例如，在某些实施方案中，提供了与包含SEQ ID NO：47的VH序列和SEQ ID NO：48的VL序列的抗RSV抗体结合相同表位的抗体。
在一个方面，本发明提供一种抗RSV抗体，其包含至少一种，两种，三种，四种，五种，或六种选自下述的CDR：(a)包含SEQ ID NO：49的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：50的氨基酸序列的CDR-H2；(c)包含SEQ ID NO：51的氨基酸序列的CDR-H3；(d)包含SEQ ID NO：52的氨基酸序列的CDR-L1；(e)包含SEQ ID NO：53的氨基酸序列的CDR-L2；和(f)包含SEQ ID NO：54的氨基酸序列的CDR-L3。
在一个方面，本发明提供一种抗体，其包含至少一种，至少两种，或所有三种选自下述的VH CDR序列：(a)包含SEQ ID NO：49的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：50的氨基酸序列的CDR-H2；和(c)包含SEQ ID NO：51的氨基酸序列的CDR-H3。在一个实施方案中，该抗体包含包含SEQ ID NO：51的氨基酸序列的CDR-H3。在另一个实施方案中，该抗体包含包含SEQ ID NO：51的氨基酸序列的CDR-H3和包含SEQ ID NO：54的氨基酸序列的CDR-L3。在又一个实施方案中，该抗体包含包含SEQ ID NO：51的氨基酸序列的CDR-H3，包含SEQ ID NO：54的氨基酸序列的CDR-L3，和包含SEQ ID NO：50的氨基酸序列的CDR-H2。在又一个实施方案中，该抗体包含(a)包含SEQ ID NO：49的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：50的氨基酸序列的CDR-H2；和(c)包含SEQ ID NO：51的氨基酸序列的CDR-H3。
在另一个方面，本发明提供一种抗体，其包含至少一种，至少两种，或所有三种选自下述的VL CDR序列：(a)包含SEQ ID NO：52的氨基酸序列的CDR-L1；(b)包含SEQ ID NO：53的氨基酸序列的CDR-L2；和(c)包含SEQ ID NO：54的氨基酸序列的CDR-L3。在一个实施方案中，该抗体包含(a)包含SEQ ID NO：52的氨基酸序列的CDR-L1；(b)包含SEQ ID NO：53的氨基酸序列的CDR-L2；和(c)包含SEQ ID NO：54的氨基酸序列的CDR-L3。
在另一个方面，本发明的抗体包含(a)包含至少一种，至少两种，或所有三种选自下述的VH CDR序列的VH域：(i)包含SEQ ID NO：49的氨基酸序列的CDR-H1，(ii)包含SEQ ID NO：50的氨基酸序列的CDR-H2，和(iii)包含SEQ ID NO：51的氨基酸序列的CDR-H3；和(b)包含至少一种，至少两种，或所有三种选自下述的VL CDR序列的VL域：(i)包含SEQ ID NO：52的氨基酸序列的CDR-L1，(ii)包含SEQ ID NO：53的氨基酸序列的CDR-L2，和(c)包含SEQ ID NO：54的氨基酸序列的CDR-L3。
在另一个方面，本发明提供一种抗体，其包含(a)包含SEQ ID NO：49的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：50的氨基酸序列的CDR-H2；(c)包含SEQ ID NO：51的氨基酸序列的CDR-H3；(d)包含SEQ ID NO：52的氨基酸序列的CDR-L1；(e)包含SEQ ID NO：53的氨基酸序列的CDR-L2；和(f)包含选自SEQ ID NO：54的氨基酸序列的CDR-L3。
在任何上述实施方案中，抗RSV抗体是人或人源化的。在一个实施方案中，抗RSV抗体包含如任何上述实施方案中的CDR，且进一步包含受体人框架，例如人免疫球蛋白框架或人共有框架。
在另一个方面，抗RSV抗体包含与SEQ ID NO：55的氨基酸序列具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，99％，或100％序列同一性的重链可变域(VH)序列。在某些实施方案中，具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，或99％同一性的VH序列相对于参照序列含有替代(例如保守替代)，***，或删除，但是包含该序列的抗RSV抗体保留结合RSV的能力。在某些实施方案中，在SEQ ID NO：55中替代，***和/或删除总共1至10个氨基酸。在某些实施方案中，替代，***，或删除在CDR以外的区域中(即在FR中)发生。任选地，该抗RSV抗体包含SEQ ID NO：55中的VH序列，包括该序列的翻译后修饰。在一个特定实施方案中，该VH包含一种，两种或三种选自下述的CDR：(a)包含SEQ ID NO：49的氨基酸序列的CDR-H1，(b)包含SEQ ID NO：50的氨基酸序列的CDR-H2，和(c)包含SEQ ID NO：51的氨基酸序列的CDR-H3。
在另一个方面，提供了一种抗RSV抗体，其中该抗体包含与SEQ ID NO：56的氨基酸序列具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，99％，或100％序列同一性的轻链可变域(VL)。在某些实施方案中，具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，或99％同一性的VL序列相对于参照序列含有替代(例如保守替代)，***，或删除，但是包含该序列的抗RSV抗体保留结合RSV的能力。在某些实施方案中，在SEQ ID NO：56中替代，***和/或删除总共1至10个氨基酸。在某些实施方案中，该替代，***，或删除在CDR以外的区域中(即在FR中)发生。任选地，该抗RSV抗体包含SEQ ID NO：56中的VL序列，包括该序列的翻译后修饰。在一个特定实施方案中，该VL包含一种，两种或三种选自下述的CDR：(a)包含SEQ ID NO：52的氨基酸序列的CDR-L1；(b)包含SEQ ID NO：53的氨基酸序列的CDR-L2；和(c)包含SEQ ID NO：54的氨基酸序列的CDR-L3。
在另一个方面，提供了一种抗RSV抗体，其中该抗体包含如任何上文提供的实施方案中的VH，和如任何上文提供的实施方案中的VL。在一个实施方案中，该抗体包含分别在SEQ ID NO：55和SEQ ID NO：56中的VH和VL序列，包括那些序列的翻译后修饰。
在又一个方面，本发明提供与本文中提供的抗RSV抗体结合相同表位的抗体。例如，在某些实施方案中，提供了与包含SEQ ID NO：55的VH序列和SEQ ID NO：56的VL序列的抗RSV抗体结合相同表位的抗体。
在一个方面，本发明提供一种抗RSV抗体，其包含至少一种，两种，三种，四种，五种，或六种选自下述的CDR：(a)包含SEQ ID NO：57的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：58的氨基酸序列的CDR-H2；(c)包含SEQ ID NO：59的氨基酸序列的CDR-H3；(d)包含SEQ ID NO：60的氨基酸序列的CDR-L1；(e)包含SEQ ID NO：61的氨基酸序列的CDR-L2；和(f)包含SEQ ID NO：62的氨基酸序列的CDR-L3。
在一个方面，本发明提供一种抗体，其包含至少一种，至少两种，或所有三种选自下述的VH CDR序列：(a)包含SEQ ID NO：57的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：58的氨基酸序列的CDR-H2；和(c)包含SEQ ID NO：59的氨基酸序列的CDR-H3。在一个实施方案中，该抗体包含包含SEQ ID NO：59的氨基酸序列的CDR-H3。在另一个实施方案中，该抗体包含包含SEQ ID NO：59的氨基酸序列的CDR-H3和包含SEQ ID NO：62的氨基酸序列的CDR-L3。在又一个实施方案中，该抗体包含包含SEQ ID NO：59的氨基酸序列的CDR-H3，包含SEQ ID NO：62的氨基酸序列的CDR-L3，和包含SEQ ID NO：58的氨基酸序列的CDR-H2。在又一个实施方案中，该抗体包含(a)包含SEQ ID NO：57的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：58的氨基酸序列的CDR-H2；和(c)包含SEQ ID NO：59的氨基酸序列的CDR-H3。
在另一个方面，本发明提供一种抗体，其包含至少一种，至少两种，或所有三种选自 下述的VL CDR序列：(a)包含SEQ ID NO：60的氨基酸序列的CDR-L1；(b)包含SEQ ID NO：61的氨基酸序列的CDR-L2；和(c)包含SEQ ID NO：62的氨基酸序列的CDR-L3。在一个实施方案中，该抗体包含(a)包含SEQ ID NO：60的氨基酸序列的CDR-L1；(b)包含SEQ ID NO：61的氨基酸序列的CDR-L2；和(c)包含SEQ ID NO：62的氨基酸序列的CDR-L3。
在另一个方面，本发明的抗体包含(a)包含至少一种，至少两种，或所有三种选自下述的VH CDR序列的VH域：(i)包含SEQ ID NO：57的氨基酸序列的CDR-H1，(ii)包含SEQ ID NO：58的氨基酸序列的CDR-H2，和(iii)包含SEQ ID NO：59的氨基酸序列的CDR-H3；和(b)包含至少一种，至少两种，或所有三种选自下述的VL CDR序列的VL域：(i)包含SEQ ID NO：60的氨基酸序列的CDR-L1，(ii)包含SEQ ID NO：61的氨基酸序列的CDR-L2，和(c)包含SEQ ID NO：62的氨基酸序列的CDR-L3。
在另一个方面，本发明提供一种抗体，其包含(a)包含SEQ ID NO：57的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：58的氨基酸序列的CDR-H2；(c)包含SEQ ID NO：59的氨基酸序列的CDR-H3；(d)包含SEQ ID NO：60的氨基酸序列的CDR-L1；(e)包含SEQ ID NO：61的氨基酸序列的CDR-L2；和(f)包含选自SEQ ID NO：62的氨基酸序列的CDR-L3。
在任何上述实施方案中，抗RSV抗体是人或人源化的。在一个实施方案中，抗RSV抗体包含如任何上述实施方案中的CDR，且进一步包含受体人框架，例如人免疫球蛋白框架或人共有框架。
在另一个方面，抗RSV抗体包含与SEQ ID NO：63的氨基酸序列具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，99％，或100％序列同一性的重链可变域(VH)序列。在某些实施方案中，具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，或99％同一性的VH序列相对于参照序列含有替代(例如保守替代)，***，或删除，但是包含该序列的抗RSV抗体保留结合RSV的能力。在某些实施方案中，在SEQ ID NO：63中替代，***和/或删除总共1至10个氨基酸。在某些实施方案中，替代，***，或删除在CDR以外的区域中(即在FR中)发生。任选地，该抗RSV抗体包含SEQ ID NO：63中的VH序列，包括该序列的翻译后修饰。在一个特定实施方案中，该VH包含一种，两种或三种选自下述的CDR：(a)包含SEQ ID NO：57的氨基酸序列的CDR-H1，(b)包含SEQ ID NO：58的氨基酸序列的CDR-H2，和(c)包含SEQ ID NO：59的氨基酸序列的CDR-H3。
在另一个方面，提供了一种抗RSV抗体，其中该抗体包含与SEQ ID NO：64的氨基酸序列具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，99％，或100％序列同一性的轻链可变域(VL)。在某些实施方案中，具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，或99％同一性的VL序列相对于参照序列含有替代(例如保守替代)，***，或删除，但是包含该序列的抗RSV抗体保留结合RSV的能力。在某些实施方案中，在SEQ ID NO：64中替代，***和/或删除总共1至10个氨基酸。在某些实施方案中，该替代，***，或删除在CDR以外的区域中(即在FR中)发生。任选地，该抗RSV抗体包含SEQ ID NO：64中的VL序列，包括该序列的翻译后修饰。在一个特定实施方案中，该VL包含一种，两种或三种选自下述的CDR：(a)包含SEQ ID NO：60的氨基酸序列的CDR-L1；(b)包含SEQ ID NO：61的氨基酸序列的CDR-L2；和(c)包含SEQ ID NO：62的氨基酸序列的CDR-L3。
在另一个方面，提供了一种抗RSV抗体，其中该抗体包含如任何上文提供的实施方案中的VH，和如任何上文提供的实施方案中的VL。在一个实施方案中，该抗体包含分别在SEQ ID NO：63和SEQ ID NO：64中的VH和VL序列，包括那些序列的翻译后修饰。
在又一个方面，本发明提供与本文中提供的抗RSV抗体结合相同表位的抗体。例如，在某些实施方案中，提供了与包含SEQ ID NO：63的VH序列和SEQ ID NO：64的VL序列的抗RSV抗体结合相同表位的抗体。
在一个方面，本发明提供一种抗RSV抗体，其包含至少一种，两种，三种，四种，五种，或六种选自下述的CDR：(a)包含SEQ ID NO：65的氨基酸序列的CDR-H1；(b)包含SEQ  ID NO：66的氨基酸序列的CDR-H2；(c)包含SEQ ID NO：67的氨基酸序列的CDR-H3；(d)包含SEQ ID NO：68的氨基酸序列的CDR-L1；(e)包含SEQ ID NO：69的氨基酸序列的CDR-L2；和(f)包含SEQ ID NO：70的氨基酸序列的CDR-L3。
在一个方面，本发明提供一种抗体，其包含至少一种，至少两种，或所有三种选自下述的VH CDR序列：(a)包含SEQ ID NO：65的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：66的氨基酸序列的CDR-H2；和(c)包含SEQ ID NO：67的氨基酸序列的CDR-H3。在一个实施方案中，该抗体包含包含SEQ ID NO：67的氨基酸序列的CDR-H3。在另一个实施方案中，该抗体包含包含SEQ ID NO：67的氨基酸序列的CDR-H3和包含SEQ ID NO：70的氨基酸序列的CDR-L3。在又一个实施方案中，该抗体包含包含SEQ ID NO：67的氨基酸序列的CDR-H3，包含SEQ ID NO：70的氨基酸序列的CDR-L3，和包含SEQ ID NO：66的氨基酸序列的CDR-H2。在又一个实施方案中，该抗体包含(a)包含SEQ ID NO：65的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：66的氨基酸序列的CDR-H2；和(c)包含SEQ ID NO：67的氨基酸序列的CDR-H3。
在另一个方面，本发明提供一种抗体，其包含至少一种，至少两种，或所有三种选自下述的VL CDR序列：(a)包含SEQ ID NO：68的氨基酸序列的CDR-L1；(b)包含SEQ ID NO：69的氨基酸序列的CDR-L2；和(c)包含SEQ ID NO：70的氨基酸序列的CDR-L3。在一个实施方案中，该抗体包含(a)包含SEQ ID NO：68的氨基酸序列的CDR-L1；(b)包含SEQ ID NO：69的氨基酸序列的CDR-L2；和(c)包含SEQ ID NO：70的氨基酸序列的CDR-L3。
在另一个方面，本发明的抗体包含(a)包含至少一种，至少两种，或所有三种选自下述的VH CDR序列的VH域：(i)包含SEQ ID NO：65的氨基酸序列的CDR-H1，(ii)包含SEQ ID NO：66的氨基酸序列的CDR-H2，和(iii)包含SEQ ID NO：67的氨基酸序列的CDR-H3；和(b)包含至少一种，至少两种，或所有三种选自下述的VL CDR序列的VL域：(i)包含SEQ ID NO：68的氨基酸序列的CDR-L1，(ii)包含SEQ ID NO：69的氨基酸序列的CDR-L2，和(c)包含SEQ ID NO：70的氨基酸序列的CDR-L3。
在另一个方面，本发明提供一种抗体，其包含(a)包含SEQ ID NO：65的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：66的氨基酸序列的CDR-H2；(c)包含SEQ ID NO：67的氨基酸序列的CDR-H3；(d)包含SEQ ID NO：68的氨基酸序列的CDR-L1；(e)包含SEQ ID NO：69的氨基酸序列的CDR-L2；和(f)包含选自SEQ ID NO：70的氨基酸序列的CDR-L3。
在任何上述实施方案中，抗RSV抗体是人或人源化的。在一个实施方案中，抗RSV抗体包含如任何上述实施方案中的CDR，且进一步包含受体人框架，例如人免疫球蛋白框架或人共有框架。
在另一个方面，抗RSV抗体包含与SEQ ID NO：71的氨基酸序列具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，99％，或100％序列同一性的重链可变域(VH)序列。在某些实施方案中，具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，或99％同一性的VH序列相对于参照序列含有替代(例如保守替代)，***，或删除，但是包含该序列的抗RSV抗体保留结合RSV的能力。在某些实施方案中，在SEQ ID NO：71中替代，***和/或删除总共1至10个氨基酸。在某些实施方案中，替代，***，或删除在CDR以外的区域中(即在FR中)发生。任选地，该抗RSV抗体包含SEQ ID NO：71中的VH序列，包括该序列的翻译后修饰。在一个特定实施方案中，该VH包含一种，两种或三种选自下述的CDR：(a)包含SEQ ID NO：65的氨基酸序列的CDR-H1，(b)包含SEQ ID NO：66的氨基酸序列的CDR-H2，和(c)包含SEQ ID NO：67的氨基酸序列的CDR-H3。
在另一个方面，提供了一种抗RSV抗体，其中该抗体包含与SEQ ID NO：72的氨基酸序列具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，99％，或100％序列同一性的轻链可变域(VL)。在某些实施方案中，具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，或99％同一性的VL序列相对于参照序列含有替代(例如保守替代)，***，或删 除，但是包含该序列的抗RSV抗体保留结合RSV的能力。在某些实施方案中，在SEQ ID NO：72中替代，***和/或删除总共1至10个氨基酸。在某些实施方案中，该替代，***，或删除在CDR以外的区域中(即在FR中)发生。任选地，该抗RSV抗体包含SEQ ID NO：72中的VL序列，包括该序列的翻译后修饰。在一个特定实施方案中，该VL包含一种，两种或三种选自下述的CDR：(a)包含SEQ ID NO：68的氨基酸序列的CDR-L1；(b)包含SEQ ID NO：69的氨基酸序列的CDR-L2；和(c)包含SEQ ID NO：70的氨基酸序列的CDR-L3。
在另一个方面，提供了一种抗RSV抗体，其中该抗体包含如任何上文提供的实施方案中的VH，和如任何上文提供的实施方案中的VL。在一个实施方案中，该抗体包含分别在SEQ ID NO：71和SEQ ID NO：72中的VH和VL序列，包括那些序列的翻译后修饰。
在又一个方面，本发明提供与本文中提供的抗RSV抗体结合相同表位的抗体。例如，在某些实施方案中，提供了与包含SEQ ID NO：71的VH序列和SEQ ID NO：72的VL序列的抗RSV抗体结合相同表位的抗体。
在一个方面，本发明提供一种抗RSV抗体，其包含至少一种，两种，三种，四种，五种，或六种选自下述的CDR：(a)包含SEQ ID NO：73的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：74的氨基酸序列的CDR-H2；(c)包含SEQ ID NO：75的氨基酸序列的CDR-H3；(d)包含SEQ ID NO：76的氨基酸序列的CDR-L1；(e)包含SEQ ID NO：77的氨基酸序列的CDR-L2；和(f)包含SEQ ID NO：78的氨基酸序列的CDR-L3。
在一个方面，本发明提供一种抗体，其包含至少一种，至少两种，或所有三种选自下述的VH CDR序列：(a)包含SEQ ID NO：73的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：74的氨基酸序列的CDR-H2；和(c)包含SEQ ID NO：75的氨基酸序列的CDR-H3。在一个实施方案中，该抗体包含包含SEQ ID NO：75的氨基酸序列的CDR-H3。在另一个实施方案中，该抗体包含包含SEQ ID NO：75的氨基酸序列的CDR-H3和包含SEQ ID NO：78的氨基酸序列的CDR-L3。在又一个实施方案中，该抗体包含包含SEQ ID NO：75的氨基酸序列的CDR-H3，包含SEQ ID NO：78的氨基酸序列的CDR-L3，和包含SEQ ID NO：74的氨基酸序列的CDR-H2。在又一个实施方案中，该抗体包含(a)包含SEQ ID NO：73的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：74的氨基酸序列的CDR-H2；和(c)包含SEQ ID NO：75的氨基酸序列的CDR-H3。
在另一个方面，本发明提供一种抗体，其包含至少一种，至少两种，或所有三种选自下述的VL CDR序列：(a)包含SEQ ID NO：76的氨基酸序列的CDR-L1；(b)包含SEQ ID NO：77的氨基酸序列的CDR-L2；和(c)包含SEQ ID NO：78的氨基酸序列的CDR-L3。在一个实施方案中，该抗体包含(a)包含SEQ ID NO：76的氨基酸序列的CDR-L1；(b)包含SEQ ID NO：77的氨基酸序列的CDR-L2；和(c)包含SEQ ID NO：78的氨基酸序列的CDR-L3。
在另一个方面，本发明的抗体包含(a)包含至少一种，至少两种，或所有三种选自下述的VH CDR序列的VH域：(i)包含SEQ ID NO：73的氨基酸序列的CDR-H1，(ii)包含SEQ ID NO：74的氨基酸序列的CDR-H2，和(iii)包含选自SEQ ID NO：75的氨基酸序列的CDR-H3；和(b)包含至少一种，至少两种，或所有三种选自下述的VL CDR序列的VL域：(i)包含SEQ ID NO：76的氨基酸序列的CDR-L1，(ii)包含SEQ ID NO：77的氨基酸序列的CDR-L2，和(c)包含SEQ ID NO：78的氨基酸序列的CDR-L3。
在另一个方面，本发明提供一种抗体，其包含(a)包含SEQ ID NO：73的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：74的氨基酸序列的CDR-H2；(c)包含SEQ ID NO：75的氨基酸序列的CDR-H3；(d)包含SEQ ID NO：76的氨基酸序列的CDR-L1；(e)包含SEQ ID NO：77的氨基酸序列的CDR-L2；和(f)包含选自SEQ ID NO：78的氨基酸序列的CDR-L3。
在任何上述实施方案中，抗RSV抗体是人或人源化的。在一个实施方案中，抗RSV抗体包含如任何上述实施方案中的CDR，且进一步包含受体人框架，例如人免疫球蛋白框架或人共有框架。
在另一个方面，抗RSV抗体包含与SEQ ID NO：79的氨基酸序列具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，99％，或100％序列同一性的重链可变域(VH)序列。在某些实施方案中，具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，或99％同一性的VH序列相对于参照序列含有替代(例如保守替代)，***，或删除，但是包含该序列的抗RSV抗体保留结合RSV的能力。在某些实施方案中，在SEQ ID NO：79中替代，***和/或删除总共1至10个氨基酸。在某些实施方案中，替代，***，或删除在CDR以外的区域中(即在FR中)发生。任选地，该抗RSV抗体包含SEQ ID NO：79中的VH序列，包括该序列的翻译后修饰。在一个特定实施方案中，该VH包含一种，两种或三种选自下述的CDR：(a)包含SEQ ID NO：73的氨基酸序列的CDR-H1，(b)包含SEQ ID NO：74的氨基酸序列的CDR-H2，和(c)包含SEQ ID NO：75的氨基酸序列的CDR-H3。
在另一个方面，提供了一种抗RSV抗体，其中该抗体包含与SEQ ID NO：80的氨基酸序列具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，99％，或100％序列同一性的轻链可变域(VL)。在某些实施方案中，具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，或99％同一性的VL序列相对于参照序列含有替代(例如保守替代)，***，或删除，但是包含该序列的抗RSV抗体保留结合RSV的能力。在某些实施方案中，在SEQ ID NO：80中替代，***和/或删除总共1至10个氨基酸。在某些实施方案中，该替代，***，或删除在CDR以外的区域中(即在FR中)发生。任选地，该抗RSV抗体包含SEQ ID NO：80中的VL序列，包括该序列的翻译后修饰。在一个特定实施方案中，该VL包含一种，两种或三种选自下述的CDR：(a)包含SEQ ID NO：76的氨基酸序列的CDR-L1；(b)包含SEQ ID NO：77的氨基酸序列的CDR-L2；和(c)包含SEQ ID NO：78的氨基酸序列的CDR-L3。
在另一个方面，提供了一种抗RSV抗体，其中该抗体包含如任何上文提供的实施方案中的VH，和如任何上文提供的实施方案中的VL。在一个实施方案中，该抗体包含分别在SEQ ID NO：79和SEQ ID NO：80中的VH和VL序列，包括那些序列的翻译后修饰。
在又一个方面，本发明提供与本文中提供的抗RSV抗体结合相同表位的抗体。例如，在某些实施方案中，提供了与包含SEQ ID NO：79的VH序列和SEQ ID NO：80的VL序列的抗RSV抗体结合相同表位的抗体。
在一个方面，本发明提供一种抗RSV抗体，其包含至少一种，两种，三种，四种，五种，或六种选自下述的CDR：(a)包含SEQ ID NO：81的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：82的氨基酸序列的CDR-H2；(c)包含SEQ ID NO：83的氨基酸序列的CDR-H3；(d)包含SEQ ID NO：84的氨基酸序列的CDR-L1；(e)包含SEQ ID NO：85的氨基酸序列的CDR-L2；和(f)包含SEQ ID NO：86的氨基酸序列的CDR-L3。
在一个方面，本发明提供一种抗体，其包含至少一种，至少两种，或所有三种选自下述的VH CDR序列：(a)包含SEQ ID NO：81的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：82的氨基酸序列的CDR-H2；和(c)包含SEQ ID NO：83的氨基酸序列的CDR-H3。在一个实施方案中，该抗体包含包含SEQ ID NO：83的氨基酸序列的CDR-H3。在另一个实施方案中，该抗体包含包含SEQ ID NO：83的氨基酸序列的CDR-H3和包含SEQ ID NO：86的氨基酸序列的CDR-L3。在又一个实施方案中，该抗体包含包含SEQ ID NO：83的氨基酸序列的CDR-H3，包含SEQ ID NO：86的氨基酸序列的CDR-L3，和包含SEQ ID NO：82的氨基酸序列的CDR-H2。在又一个实施方案中，该抗体包含(a)包含SEQ ID NO：81的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：82的氨基酸序列的CDR-H2；和(c)包含SEQ ID NO：83的氨基酸序列的CDR-H3。
在另一个方面，本发明提供一种抗体，其包含至少一种，至少两种，或所有三种选自下述的VL CDR序列：(a)包含SEQ ID NO：84的氨基酸序列的CDR-L1；(b)包含SEQ ID NO：85的氨基酸序列的CDR-L2；和(c)包含SEQ ID NO：86的氨基酸序列的CDR-L3。在一个实施方案中，该抗体包含(a)包含SEQ ID NO：84的氨基酸序列的CDR-L1；(b)包含SEQ ID  NO：85的氨基酸序列的CDR-L2；和(c)包含SEQ ID NO：86的氨基酸序列的CDR-L3。
在另一个方面，本发明的抗体包含(a)包含至少一种，至少两种，或所有三种选自下述的VH CDR序列的VH域：(i)包含SEQ ID NO：81的氨基酸序列的CDR-H1，(ii)包含SEQ ID NO：82的氨基酸序列的CDR-H2，和(iii)包含选自SEQ ID NO：83的氨基酸序列的CDR-H3；和(b)包含至少一种，至少两种，或所有三种选自下述的VL CDR序列的VL域：(i)包含SEQ ID NO：84的氨基酸序列的CDR-L1，(ii)包含SEQ ID NO：85的氨基酸序列的CDR-L2，和(c)包含SEQ ID NO：86的氨基酸序列的CDR-L3。
在另一个方面，本发明提供一种抗体，其包含(a)包含SEQ ID NO：81的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：82的氨基酸序列的CDR-H2；(c)包含SEQ ID NO：83的氨基酸序列的CDR-H3；(d)包含SEQ ID NO：84的氨基酸序列的CDR-L1；(e)包含SEQ ID NO：85的氨基酸序列的CDR-L2；和(f)包含选自SEQ ID NO：86的氨基酸序列的CDR-L3。
在任何上述实施方案中，抗RSV抗体是人或人源化的。在一个实施方案中，抗RSV抗体包含如任何上述实施方案中的CDR，且进一步包含受体人框架，例如人免疫球蛋白框架或人共有框架。
在另一个方面，抗RSV抗体包含与SEQ ID NO：87的氨基酸序列具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，99％，或100％序列同一性的重链可变域(VH)序列。在某些实施方案中，具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，或99％同一性的VH序列相对于参照序列含有替代(例如保守替代)，***，或删除，但是包含该序列的抗RSV抗体保留结合RSV的能力。在某些实施方案中，在SEQ ID NO：87中替代，***和/或删除总共1至10个氨基酸。在某些实施方案中，替代，***，或删除在CDR以外的区域中(即在FR中)发生。任选地，该抗RSV抗体包含SEQ ID NO：87中的VH序列，包括该序列的翻译后修饰。在一个特定实施方案中，该VH包含一种，两种或三种选自下述的CDR：(a)包含SEQ ID NO：81的氨基酸序列的CDR-H1，(b)包含SEQ ID NO：82的氨基酸序列的CDR-H2，和(c)包含SEQ ID NO：83的氨基酸序列的CDR-H3。
在另一个方面，提供了一种抗RSV抗体，其中该抗体包含与SEQ ID NO：88的氨基酸序列具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，99％，或100％序列同一性的轻链可变域(VL)。在某些实施方案中，具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，或99％同一性的VL序列相对于参照序列含有替代(例如保守替代)，***，或删除，但是包含该序列的抗RSV抗体保留结合RSV的能力。在某些实施方案中，在SEQ ID NO：88中替代，***和/或删除总共1至10个氨基酸。在某些实施方案中，该替代，***，或删除在CDR以外的区域中(即在FR中)发生。任选地，该抗RSV抗体包含SEQ ID NO：88中的VL序列，包括该序列的翻译后修饰。在一个特定实施方案中，该VL包含一种，两种或三种选自下述的CDR：(a)包含SEQ ID NO：84的氨基酸序列的CDR-L1；(b)包含SEQ ID NO：85的氨基酸序列的CDR-L2；和(c)包含SEQ ID NO：86的氨基酸序列的CDR-L3。
在另一个方面，提供了一种抗RSV抗体，其中该抗体包含如任何上文提供的实施方案中的VH，和如任何上文提供的实施方案中的VL。在一个实施方案中，该抗体包含分别在SEQ ID NO：87和SEQ ID NO：88中的VH和VL序列，包括那些序列的翻译后修饰。
在又一个方面，本发明提供与本文中提供的抗RSV抗体结合相同表位的抗体。例如，在某些实施方案中，提供了与包含SEQ ID NO：87的VH序列和SEQ ID NO：88的VL序列的抗RSV抗体结合相同表位的抗体。
在一个方面，本发明提供一种抗RSV抗体，其包含至少一种，两种，三种，四种，五种，或六种选自下述的CDR：(a)包含SEQ ID NO：89的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：90的氨基酸序列的CDR-H2；(c)包含SEQ ID NO：91的氨基酸序列的CDR-H3；(d)包含SEQ ID NO：92的氨基酸序列的CDR-L1；(e)包含SEQ ID NO：93的氨基酸序列的CDR-L2；和(f)包含SEQ ID NO：94的氨基酸序列的CDR-L3。
在一个方面，本发明提供一种抗体，其包含至少一种，至少两种，或所有三种选自下述的VH CDR序列：(a)包含SEQ ID NO：89的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：90的氨基酸序列的CDR-H2；和(c)包含SEQ ID NO：91的氨基酸序列的CDR-H3。在一个实施方案中，该抗体包含包含SEQ ID NO：91的氨基酸序列的CDR-H3。在另一个实施方案中，该抗体包含包含SEQ ID NO：91的氨基酸序列的CDR-H3和包含SEQ ID NO：94的氨基酸序列的CDR-L3。在又一个实施方案中，该抗体包含包含SEQ ID NO：91的氨基酸序列的CDR-H3，包含SEQ ID NO：94的氨基酸序列的CDR-L3，和包含SEQ ID NO：90的氨基酸序列的CDR-H2。在又一个实施方案中，该抗体包含(a)包含SEQ ID NO：89的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：90的氨基酸序列的CDR-H2；和(c)包含SEQ ID NO：91的氨基酸序列的CDR-H3。
在另一个方面，本发明提供一种抗体，其包含至少一种，至少两种，或所有三种选自下述的VL CDR序列：(a)包含SEQ ID NO：92的氨基酸序列的CDR-L1；(b)包含SEQ ID NO：93的氨基酸序列的CDR-L2；和(c)包含SEQ ID NO：94的氨基酸序列的CDR-L3。在一个实施方案中，该抗体包含(a)包含SEQ ID NO：92的氨基酸序列的CDR-L1；(b)包含SEQ ID NO：93的氨基酸序列的CDR-L2；和(c)包含SEQ ID NO：94的氨基酸序列的CDR-L3。
在另一个方面，本发明的抗体包含(a)包含至少一种，至少两种，或所有三种选自下述的VH CDR序列的VH域：(i)包含SEQ ID NO：89的氨基酸序列的CDR-H1，(ii)包含SEQ ID NO：90的氨基酸序列的CDR-H2，和(iii)包含选自SEQ ID NO：91的氨基酸序列的CDR-H3；和(b)包含至少一种，至少两种，或所有三种选自下述的VL CDR序列的VL域：(i)包含SEQ ID NO：92的氨基酸序列的CDR-L1，(ii)包含SEQ ID NO：93的氨基酸序列的CDR-L2，和(c)包含SEQ ID NO：94的氨基酸序列的CDR-L3。
在另一个方面，本发明提供一种抗体，其包含(a)包含SEQ ID NO：89的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：90的氨基酸序列的CDR-H2；(c)包含SEQ ID NO：91的氨基酸序列的CDR-H3；(d)包含SEQ ID NO：92的氨基酸序列的CDR-L1；(e)包含SEQ ID NO：93的氨基酸序列的CDR-L2；和(f)包含选自SEQ ID NO：94的氨基酸序列的CDR-L3。
在任何上述实施方案中，抗RSV抗体是人或人源化的。在一个实施方案中，抗RSV抗体包含如任何上述实施方案中的CDR，且进一步包含受体人框架，例如人免疫球蛋白框架或人共有框架。
在另一个方面，抗RSV抗体包含与SEQ ID NO：95的氨基酸序列具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，99％，或100％序列同一性的重链可变域(VH)序列。在某些实施方案中，具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，或99％同一性的VH序列相对于参照序列含有替代(例如保守替代)，***，或删除，但是包含该序列的抗RSV抗体保留结合RSV的能力。在某些实施方案中，在SEQ ID NO：95中替代，***和/或删除总共1至10个氨基酸。在某些实施方案中，替代，***，或删除在CDR以外的区域中(即在FR中)发生。任选地，该抗RSV抗体包含SEQ ID NO：95中的VH序列，包括该序列的翻译后修饰。在一个特定实施方案中，该VH包含一种，两种或三种选自下述的CDR：(a)包含SEQ ID NO：89的氨基酸序列的CDR-H1，(b)包含SEQ ID NO：90的氨基酸序列的CDR-H2，和(c)包含SEQ ID NO：91的氨基酸序列的CDR-H3。
在另一个方面，提供了一种抗RSV抗体，其中该抗体包含与SEQ ID NO：96的氨基酸序列具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，99％，或100％序列同一性的轻链可变域(VL)。在某些实施方案中，具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，或99％同一性的VL序列相对于参照序列含有替代(例如保守替代)，***，或删除，但是包含该序列的抗RSV抗体保留结合RSV的能力。在某些实施方案中，在SEQ ID NO：96中替代，***和/或删除总共1至10个氨基酸。在某些实施方案中，该替代，***，或删除在CDR以外的区域中(即在FR中)发生。任选地，该抗RSV抗体包含SEQ ID NO：96中 的VL序列，包括该序列的翻译后修饰。在一个特定实施方案中，该VL包含一种，两种或三种选自下述的CDR：(a)包含SEQ ID NO：92的氨基酸序列的CDR-L1；(b)包含SEQ ID NO：93的氨基酸序列的CDR-L2；和(c)包含SEQ ID NO：94的氨基酸序列的CDR-L3。
在另一个方面，提供了一种抗RSV抗体，其中该抗体包含如任何上文提供的实施方案中的VH，和如任何上文提供的实施方案中的VL。在一个实施方案中，该抗体包含分别在SEQ ID NO：95和SEQ ID NO：96中的VH和VL序列，包括那些序列的翻译后修饰。
在又一个方面，本发明提供与本文中提供的抗RSV抗体结合相同表位的抗体。例如，在某些实施方案中，提供了与包含SEQ ID NO：95的VH序列和SEQ ID NO：96的VL序列的抗RSV抗体结合相同表位的抗体。
在一个方面，本发明提供一种抗RSV抗体，其包含至少一种，两种，三种，四种，五种，或六种选自下述的CDR：(a)包含SEQ ID NO：97的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：98的氨基酸序列的CDR-H2；(c)包含SEQ ID NO：99的氨基酸序列的CDR-H3；(d)包含SEQ ID NO：100的氨基酸序列的CDR-L1；(e)包含SEQ ID NO：101的氨基酸序列的CDR-L2；和(f)包含SEQ ID NO：102的氨基酸序列的CDR-L3。
在一个方面，本发明提供一种抗体，其包含至少一种，至少两种，或所有三种选自下述的VH CDR序列：(a)包含SEQ ID NO：97的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：98的氨基酸序列的CDR-H2；和(c)包含SEQ ID NO：99的氨基酸序列的CDR-H3。在一个实施方案中，该抗体包含包含SEQ ID NO：99的氨基酸序列的CDR-H3。在另一个实施方案中，该抗体包含包含SEQ ID NO：99的氨基酸序列的CDR-H3和包含SEQ ID NO：102的氨基酸序列的CDR-L3。在又一个实施方案中，该抗体包含包含SEQ ID NO：99的氨基酸序列的CDR-H3，包含SEQ ID NO：102的氨基酸序列的CDR-L3，和包含SEQ ID NO：98的氨基酸序列的CDR-H2。在又一个实施方案中，该抗体包含(a)包含SEQ ID NO：97的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：98的氨基酸序列的CDR-H2；和(c)包含SEQ ID NO：99的氨基酸序列的CDR-H3。
在另一个方面，本发明提供一种抗体，其包含至少一种，至少两种，或所有三种选自下述的VL CDR序列：(a)包含SEQ ID NO：100的氨基酸序列的CDR-L1；(b)包含SEQ ID NO：101的氨基酸序列的CDR-L2；和(c)包含SEQ ID NO：102的氨基酸序列的CDR-L3。在一个实施方案中，该抗体包含(a)包含SEQ ID NO：100的氨基酸序列的CDR-L1；(b)包含SEQ ID NO：101的氨基酸序列的CDR-L2；和(c)包含SEQ ID NO：102的氨基酸序列的CDR-L3。
在另一个方面，本发明的抗体包含(a)包含至少一种，至少两种，或所有三种选自下述的VH CDR序列的VH域：(i)包含SEQ ID NO：97的氨基酸序列的CDR-H1，(ii)包含SEQ ID NO：98的氨基酸序列的CDR-H2，和(iii)包含选自SEQ ID NO：99的氨基酸序列的CDR-H3；和(b)包含至少一种，至少两种，或所有三种选自下述的VL CDR序列的VL域：(i)包含SEQ ID NO：100的氨基酸序列的CDR-L1，(ii)包含SEQ ID NO：101的氨基酸序列的CDR-L2，和(c)包含SEQ ID NO：102的氨基酸序列的CDR-L3。
在另一个方面，本发明提供一种抗体，其包含(a)包含SEQ ID NO：97的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：98的氨基酸序列的CDR-H2；(c)包含SEQ ID NO：99的氨基酸序列的CDR-H3；(d)包含SEQ ID NO：100的氨基酸序列的CDR-L1；(e)包含SEQ ID NO：101的氨基酸序列的CDR-L2；和(f)包含选自SEQ ID NO：102的氨基酸序列的CDR-L3。
在任何上述实施方案中，抗RSV抗体是人或人源化的。在一个实施方案中，抗RSV抗体包含如任何上述实施方案中的CDR，且进一步包含受体人框架，例如人免疫球蛋白框架或人共有框架。
在另一个方面，抗RSV抗体包含与SEQ ID NO：103的氨基酸序列具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，99％，或100％序列同一性的重链可变域(VH)序列。 在某些实施方案中，具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，或99％同一性的VH序列相对于参照序列含有替代(例如保守替代)，***，或删除，但是包含该序列的抗RSV抗体保留结合RSV的能力。在某些实施方案中，在SEQ ID NO：103中替代，***和/或删除总共1至10个氨基酸。在某些实施方案中，替代，***，或删除在CDR以外的区域中(即在FR中)发生。任选地，该抗RSV抗体包含SEQ ID NO：103中的VH序列，包括该序列的翻译后修饰。在一个特定实施方案中，该VH包含一种，两种或三种选自下述的CDR：(a)包含SEQ ID NO：97的氨基酸序列的CDR-H1，(b)包含SEQ ID NO：98的氨基酸序列的CDR-H2，和(c)包含SEQ ID NO：99的氨基酸序列的CDR-H3。
在另一个方面，提供了一种抗RSV抗体，其中该抗体包含与SEQ ID NO：104的氨基酸序列具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，99％，或100％序列同一性的轻链可变域(VL)。在某些实施方案中，具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，或99％同一性的VL序列相对于参照序列含有替代(例如保守替代)，***，或删除，但是包含该序列的抗RSV抗体保留结合RSV的能力。在某些实施方案中，在SEQ ID NO：104中替代，***和/或删除总共1至10个氨基酸。在某些实施方案中，该替代，***，或删除在CDR以外的区域中(即在FR中)发生。任选地，该抗RSV抗体包含SEQ ID NO：104中的VL序列，包括该序列的翻译后修饰。在一个特定实施方案中，该VL包含一种，两种或三种选自下述的CDR：(a)包含SEQ ID NO：100的氨基酸序列的CDR-L1；(b)包含SEQ ID NO：101的氨基酸序列的CDR-L2；和(c)包含SEQ ID NO：102的氨基酸序列的CDR-L3。
在另一个方面，提供了一种抗RSV抗体，其中该抗体包含如任何上文提供的实施方案中的VH，和如任何上文提供的实施方案中的VL。在一个实施方案中，该抗体包含分别在SEQ ID NO：103和SEQ ID NO：104中的VH和VL序列，包括那些序列的翻译后修饰。
在又一个方面，本发明提供与本文中提供的抗RSV抗体结合相同表位的抗体。例如，在某些实施方案中，提供了与包含SEQ ID NO：103的VH序列和SEQ ID NO：104的VL序列的抗RSV抗体结合相同表位的抗体。
在一个方面，本发明提供一种抗RSV抗体，其包含至少一种，两种，三种，四种，五种，或六种选自下述的CDR：(a)包含SEQ ID NO：105的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：106的氨基酸序列的CDR-H2；(c)包含SEQ ID NO：107的氨基酸序列的CDR-H3；(d)包含SEQ ID NO：108的氨基酸序列的CDR-L1；(e)包含SEQ ID NO：109的氨基酸序列的CDR-L2；和(f)包含SEQ ID NO：110的氨基酸序列的CDR-L3。
在一个方面，本发明提供一种抗体，其包含至少一种，至少两种，或所有三种选自下述的VH CDR序列：(a)包含SEQ ID NO：105的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：106的氨基酸序列的CDR-H2；和(c)包含SEQ ID NO：107的氨基酸序列的CDR-H3。在一个实施方案中，该抗体包含包含SEQ ID NO：107的氨基酸序列的CDR-H3。在另一个实施方案中，该抗体包含包含SEQ ID NO：107的氨基酸序列的CDR-H3和包含SEQ ID NO：110的氨基酸序列的CDR-L3。在又一个实施方案中，该抗体包含包含SEQ ID NO：107的氨基酸序列的CDR-H3，包含SEQ ID NO：110的氨基酸序列的CDR-L3，和包含SEQ ID NO：106的氨基酸序列的CDR-H2。在又一个实施方案中，该抗体包含(a)包含SEQ ID NO：105的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：106的氨基酸序列的CDR-H2；和(c)包含SEQ ID NO：107的氨基酸序列的CDR-H3。
在另一个方面，本发明提供一种抗体，其包含至少一种，至少两种，或所有三种选自下述的VL CDR序列：(a)包含SEQ ID NO：108的氨基酸序列的CDR-L1；(b)包含SEQ ID NO：109的氨基酸序列的CDR-L2；和(c)包含SEQ ID NO：110的氨基酸序列的CDR-L3。在一个实施方案中，该抗体包含(a)包含SEQ ID NO：108的氨基酸序列的CDR-L1；(b)包含SEQ ID NO：109的氨基酸序列的CDR-L2；和(c)包含SEQ ID NO：110的氨基酸序列的CDR-L3。
在另一个方面，本发明的抗体包含(a)包含至少一种，至少两种，或所有三种选自下述的VH CDR序列的VH域：(i)包含SEQ ID NO：105的氨基酸序列的CDR-H1，(ii)包含SEQ ID NO：106的氨基酸序列的CDR-H2，和(iii)包含选自SEQ ID NO：107的氨基酸序列的CDR-H3；和(b)包含至少一种，至少两种，或所有三种选自下述的VL CDR序列的VL域：(i)包含SEQ ID NO：108的氨基酸序列的CDR-L1，(ii)包含SEQ ID NO：109的氨基酸序列的CDR-L2，和(c)包含SEQ ID NO：110的氨基酸序列的CDR-L3。
在另一个方面，本发明提供一种抗体，其包含(a)包含SEQ ID NO：105的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：106的氨基酸序列的CDR-H2；(c)包含SEQ ID NO：107的氨基酸序列的CDR-H3；(d)包含SEQ ID NO：108的氨基酸序列的CDR-L1；(e)包含SEQ ID NO：109的氨基酸序列的CDR-L2；和(f)包含选自SEQ ID NO：110的氨基酸序列的CDR-L3。
在任何上述实施方案中，抗RSV抗体是人或人源化的。在一个实施方案中，抗RSV抗体包含如任何上述实施方案中的CDR，且进一步包含受体人框架，例如人免疫球蛋白框架或人共有框架。
在另一个方面，抗RSV抗体包含与SEQ ID NO：111的氨基酸序列具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，99％，或100％序列同一性的重链可变域(VH)序列。在某些实施方案中，具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，或99％同一性的VH序列相对于参照序列含有替代(例如保守替代)，***，或删除，但是包含该序列的抗RSV抗体保留结合RSV的能力。在某些实施方案中，在SEQ ID NO：111中替代，***和/或删除总共1至10个氨基酸。在某些实施方案中，替代，***，或删除在CDR以外的区域中(即在FR中)发生。任选地，该抗RSV抗体包含SEQ ID NO：111中的VH序列，包括该序列的翻译后修饰。在一个特定实施方案中，该VH包含一种，两种或三种选自下述的CDR：(a)包含SEQ ID NO：105的氨基酸序列的CDR-H1，(b)包含SEQ ID NO：106的氨基酸序列的CDR-H2，和(c)包含SEQ ID NO：107的氨基酸序列的CDR-H3。
在另一个方面，提供了一种抗RSV抗体，其中该抗体包含与SEQ ID NO：112的氨基酸序列具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，99％，或100％序列同一性的轻链可变域(VL)。在某些实施方案中，具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，或99％同一性的VL序列相对于参照序列含有替代(例如保守替代)，***，或删除，但是包含该序列的抗RSV抗体保留结合RSV的能力。在某些实施方案中，在SEQ ID NO：112中替代，***和/或删除总共1至10个氨基酸。在某些实施方案中，该替代，***，或删除在CDR以外的区域中(即在FR中)发生。任选地，该抗RSV抗体包含SEQ ID NO：112中的VL序列，包括该序列的翻译后修饰。在一个特定实施方案中，该VL包含一种，两种或三种选自下述的CDR：(a)包含SEQ ID NO：108的氨基酸序列的CDR-L1；(b)包含SEQ ID NO：109的氨基酸序列的CDR-L2；和(c)包含SEQ ID NO：110的氨基酸序列的CDR-L3。
在另一个方面，提供了一种抗RSV抗体，其中该抗体包含如任何上文提供的实施方案中的VH，和如任何上文提供的实施方案中的VL。在一个实施方案中，该抗体包含分别在SEQ ID NO：111和SEQ ID NO：112中的VH和VL序列，包括那些序列的翻译后修饰。
在又一个方面，本发明提供与本文中提供的抗RSV抗体结合相同表位的抗体。例如，在某些实施方案中，提供了与包含SEQ ID NO：111的VH序列和SEQ ID NO：112的VL序列的抗RSV抗体结合相同表位的抗体。
在一个方面，本发明提供一种抗RSV抗体，其包含至少一种，两种，三种，四种，五种，或六种选自下述的CDR：(a)包含SEQ ID NO：113的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：114的氨基酸序列的CDR-H2；(c)包含SEQ ID NO：115的氨基酸序列的CDR-H3；(d)包含SEQ ID NO：116的氨基酸序列的CDR-L1；(e)包含SEQ ID NO：117的氨基酸序列的CDR-L2；和(f)包含SEQ ID NO：118的氨基酸序列的CDR-L3。
在一个方面，本发明提供一种抗体，其包含至少一种，至少两种，或所有三种选自下述的VH CDR序列：(a)包含SEQ ID NO：113的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：114的氨基酸序列的CDR-H2；和(c)包含SEQ ID NO：115的氨基酸序列的CDR-H3。在一个实施方案中，该抗体包含包含SEQ ID NO：115的氨基酸序列的CDR-H3。在另一个实施方案中，该抗体包含包含SEQ ID NO：115的氨基酸序列的CDR-H3和包含SEQ ID NO：118的氨基酸序列的CDR-L3。在又一个实施方案中，该抗体包含包含SEQ ID NO：115的氨基酸序列的CDR-H3，包含SEQ ID NO：118的氨基酸序列的CDR-L3，和包含SEQ ID NO：114的氨基酸序列的CDR-H2。在又一个实施方案中，该抗体包含(a)包含SEQ ID NO：113的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：114的氨基酸序列的CDR-H2；和(c)包含SEQ ID NO：115的氨基酸序列的CDR-H3。
在另一个方面，本发明提供一种抗体，其包含至少一种，至少两种，或所有三种选自下述的VL CDR序列：(a)包含SEQ ID NO：116的氨基酸序列的CDR-L1；(b)包含SEQ ID NO：117的氨基酸序列的CDR-L2；和(c)包含SEQ ID NO：118的氨基酸序列的CDR-L3。在一个实施方案中，该抗体包含(a)包含SEQ ID NO：116的氨基酸序列的CDR-L1；(b)包含SEQ ID NO：117的氨基酸序列的CDR-L2；和(c)包含SEQ ID NO：118的氨基酸序列的CDR-L3。
在另一个方面，本发明的抗体包含(a)包含至少一种，至少两种，或所有三种选自下述的VH CDR序列的VH域：(i)包含SEQ ID NO：113的氨基酸序列的CDR-H1，(ii)包含SEQ ID NO：114的氨基酸序列的CDR-H2，和(iii)包含选自SEQ ID NO：115的氨基酸序列的CDR-H3；和(b)包含至少一种，至少两种，或所有三种选自下述的VL CDR序列的VL域：(i)包含SEQ ID NO：116的氨基酸序列的CDR-L1，(ii)包含SEQ ID NO：117的氨基酸序列的CDR-L2，和(c)包含SEQ ID NO：118的氨基酸序列的CDR-L3。
在另一个方面，本发明提供一种抗体，其包含(a)包含SEQ ID NO：113的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：114的氨基酸序列的CDR-H2；(c)包含SEQ ID NO：115的氨基酸序列的CDR-H3；(d)包含SEQ ID NO：116的氨基酸序列的CDR-L1；(e)包含SEQ ID NO：117的氨基酸序列的CDR-L2；和(f)包含选自SEQ ID NO：118的氨基酸序列的CDR-L3。
在任何上述实施方案中，抗RSV抗体是人或人源化的。在一个实施方案中，抗RSV抗体包含如任何上述实施方案中的CDR，且进一步包含受体人框架，例如人免疫球蛋白框架或人共有框架。
在另一个方面，抗RSV抗体包含与SEQ ID NO：119的氨基酸序列具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，99％，或100％序列同一性的重链可变域(VH)序列。在某些实施方案中，具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，或99％同一性的VH序列相对于参照序列含有替代(例如保守替代)，***，或删除，但是包含该序列的抗RSV抗体保留结合RSV的能力。在某些实施方案中，在SEQ ID NO：119中替代，***和/或删除总共1至10个氨基酸。在某些实施方案中，替代，***，或删除在CDR以外的区域中(即在FR中)发生。任选地，该抗RSV抗体包含SEQ ID NO：119中的VH序列，包括该序列的翻译后修饰。在一个特定实施方案中，该VH包含一种，两种或三种选自下述的CDR：(a)包含SEQ ID NO：113的氨基酸序列的CDR-H1，(b)包含SEQ ID NO：114的氨基酸序列的CDR-H2，和(c)包含SEQ ID NO：115的氨基酸序列的CDR-H3。
在另一个方面，提供了一种抗RSV抗体，其中该抗体包含与SEQ ID NO：120的氨基酸序列具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，99％，或100％序列同一性的轻链可变域(VL)。在某些实施方案中，具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，或99％同一性的VL序列相对于参照序列含有替代(例如保守替代)，***，或删除，但是包含该序列的抗RSV抗体保留结合RSV的能力。在某些实施方案中，在SEQ ID  NO：120中替代，***和/或删除总共1至10个氨基酸。在某些实施方案中，该替代，***，或删除在CDR以外的区域中(即在FR中)发生。任选地，该抗RSV抗体包含SEQ ID NO：120中的VL序列，包括该序列的翻译后修饰。在一个特定实施方案中，该VL包含一种，两种或三种选自下述的CDR：(a)包含SEQ ID NO：116的氨基酸序列的CDR-L1；(b)包含SEQ ID NO：117的氨基酸序列的CDR-L2；和(c)包含SEQ ID NO：118的氨基酸序列的CDR-L3。
在另一个方面，提供了一种抗RSV抗体，其中该抗体包含如任何上文提供的实施方案中的VH，和如任何上文提供的实施方案中的VL。在一个实施方案中，该抗体包含分别在SEQ ID NO：119和SEQ ID NO：120中的VH和VL序列，包括那些序列的翻译后修饰。
在又一个方面，本发明提供与本文中提供的抗RSV抗体结合相同表位的抗体。例如，在某些实施方案中，提供了与包含SEQ ID NO：119的VH序列和SEQ ID NO：120的VL序列的抗RSV抗体结合相同表位的抗体。
在一个方面，本发明提供一种抗RSV抗体，其包含至少一种，两种，三种，四种，五种，或六种选自下述的CDR：(a)包含SEQ ID NO：121的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：122的氨基酸序列的CDR-H2；(c)包含SEQ ID NO：123的氨基酸序列的CDR-H3；(d)包含SEQ ID NO：124的氨基酸序列的CDR-L1；(e)包含SEQ ID NO：125的氨基酸序列的CDR-L2；和(f)包含SEQ ID NO：126的氨基酸序列的CDR-L3。
在一个方面，本发明提供一种抗体，其包含至少一种，至少两种，或所有三种选自下述的VH CDR序列：(a)包含SEQ ID NO：121的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：122的氨基酸序列的CDR-H2；和(c)包含SEQ ID NO：123的氨基酸序列的CDR-H3。在一个实施方案中，该抗体包含包含SEQ ID NO：123的氨基酸序列的CDR-H3。在另一个实施方案中，该抗体包含包含SEQ ID NO：123的氨基酸序列的CDR-H3和包含SEQ ID NO：126的氨基酸序列的CDR-L3。在又一个实施方案中，该抗体包含包含SEQ ID NO：123的氨基酸序列的CDR-H3，包含SEQ ID NO：126的氨基酸序列的CDR-L3，和包含SEQ ID NO：122的氨基酸序列的CDR-H2。在又一个实施方案中，该抗体包含(a)包含SEQ ID NO：121的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：122的氨基酸序列的CDR-H2；和(c)包含SEQ ID NO：123的氨基酸序列的CDR-H3。
在另一个方面，本发明提供一种抗体，其包含至少一种，至少两种，或所有三种选自下述的VL CDR序列：(a)包含SEQ ID NO：124的氨基酸序列的CDR-L1；(b)包含SEQ ID NO：125的氨基酸序列的CDR-L2；和(c)包含SEQ ID NO：126的氨基酸序列的CDR-L3。在一个实施方案中，该抗体包含(a)包含SEQ ID NO：124的氨基酸序列的CDR-L1；(b)包含SEQ ID NO：125的氨基酸序列的CDR-L2；和(c)包含SEQ ID NO：126的氨基酸序列的CDR-L3。
在另一个方面，本发明的抗体包含(a)包含至少一种，至少两种，或所有三种选自下述的VH CDR序列的VH域：(i)包含SEQ ID NO：121的氨基酸序列的CDR-H1，(ii)包含SEQ ID NO：122的氨基酸序列的CDR-H2，和(iii)包含选自SEQ ID NO：123的氨基酸序列的CDR-H3；和(b)包含至少一种，至少两种，或所有三种选自下述的VL CDR序列的VL域：(i)包含SEQ ID NO：124的氨基酸序列的CDR-L1，(ii)包含SEQ ID NO：125的氨基酸序列的CDR-L2，和(c)包含SEQ ID NO：126的氨基酸序列的CDR-L3。
在另一个方面，本发明提供一种抗体，其包含(a)包含SEQ ID NO：121的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：122的氨基酸序列的CDR-H2；(c)包含SEQ ID NO：123的氨基酸序列的CDR-H3；(d)包含SEQ ID NO：124的氨基酸序列的CDR-L1；(e)包含SEQ ID NO：125的氨基酸序列的CDR-L2；和(f)包含选自SEQ ID NO：126的氨基酸序列的CDR-L3。
在任何上述实施方案中，抗RSV抗体是人或人源化的。在一个实施方案中，抗RSV抗体包含如任何上述实施方案中的CDR，且进一步包含受体人框架，例如人免疫球蛋白框 架或人共有框架。
在另一个方面，抗RSV抗体包含与SEQ ID NO：127的氨基酸序列具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，99％，或100％序列同一性的重链可变域(VH)序列。在某些实施方案中，具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，或99％同一性的VH序列相对于参照序列含有替代(例如保守替代)，***，或删除，但是包含该序列的抗RSV抗体保留结合RSV的能力。在某些实施方案中，在SEQ ID NO：127中替代，***和/或删除总共1至10个氨基酸。在某些实施方案中，替代，***，或删除在CDR以外的区域中(即在FR中)发生。任选地，该抗RSV抗体包含SEQ ID NO：127中的VH序列，包括该序列的翻译后修饰。在一个特定实施方案中，该VH包含一种，两种或三种选自下述的CDR：(a)包含SEQ ID NO：121的氨基酸序列的CDR-H1，(b)包含SEQ ID NO：122的氨基酸序列的CDR-H2，和(c)包含SEQ ID NO：123的氨基酸序列的CDR-H3。
在另一个方面，提供了一种抗RSV抗体，其中该抗体包含与SEQ ID NO：128的氨基酸序列具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，99％，或100％序列同一性的轻链可变域(VL)。在某些实施方案中，具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，或99％同一性的VL序列相对于参照序列含有替代(例如保守替代)，***，或删除，但是包含该序列的抗RSV抗体保留结合RSV的能力。在某些实施方案中，在SEQ ID NO：128中替代，***和/或删除总共1至10个氨基酸。在某些实施方案中，该替代，***，或删除在CDR以外的区域中(即在FR中)发生。任选地，该抗RSV抗体包含SEQ ID NO：128中的VL序列，包括该序列的翻译后修饰。在一个特定实施方案中，该VL包含一种，两种或三种选自下述的CDR：(a)包含SEQ ID NO：124的氨基酸序列的CDR-L1；(b)包含SEQ ID NO：125的氨基酸序列的CDR-L2；和(c)包含SEQ ID NO：126的氨基酸序列的CDR-L3。
在另一个方面，提供了一种抗RSV抗体，其中该抗体包含如任何上文提供的实施方案中的VH，和如任何上文提供的实施方案中的VL。在一个实施方案中，该抗体包含分别在SEQ ID NO：127和SEQ ID NO：128中的VH和VL序列，包括那些序列的翻译后修饰。
在又一个方面，本发明提供与本文中提供的抗RSV抗体结合相同表位的抗体。例如，在某些实施方案中，提供了与包含SEQ ID NO：127的VH序列和SEQ ID NO：128的VL序列的抗RSV抗体结合相同表位的抗体。
在一个方面，本发明提供一种抗RSV抗体，其包含至少一种，两种，三种，四种，五种，或六种选自下述的CDR：(a)包含SEQ ID NO：129的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：130的氨基酸序列的CDR-H2；(c)包含SEQ ID NO：131的氨基酸序列的CDR-H3；(d)包含SEQ ID NO：132的氨基酸序列的CDR-L1；(e)包含SEQ ID NO：133的氨基酸序列的CDR-L2；和(f)包含SEQ ID NO：134的氨基酸序列的CDR-L3。
在一个方面，本发明提供一种抗体，其包含至少一种，至少两种，或所有三种选自下述的VH CDR序列：(a)包含SEQ ID NO：129的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：130的氨基酸序列的CDR-H2；和(c)包含SEQ ID NO：131的氨基酸序列的CDR-H3。在一个实施方案中，该抗体包含包含SEQ ID NO：131的氨基酸序列的CDR-H3。在另一个实施方案中，该抗体包含包含SEQ ID NO：131的氨基酸序列的CDR-H3和包含SEQ ID NO：134的氨基酸序列的CDR-L3。在又一个实施方案中，该抗体包含包含SEQ ID NO：131的氨基酸序列的CDR-H3，包含SEQ ID NO：134的氨基酸序列的CDR-L3，和包含SEQ ID NO：130的氨基酸序列的CDR-H2。在又一个实施方案中，该抗体包含(a)包含SEQ ID NO：129的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：130的氨基酸序列的CDR-H2；和(c)包含SEQ ID NO：131的氨基酸序列的CDR-H3。
在另一个方面，本发明提供一种抗体，其包含至少一种，至少两种，或所有三种选自下述的VL CDR序列：(a)包含SEQ ID NO：132的氨基酸序列的CDR-L1；(b)包含SEQ ID NO：133的氨基酸序列的CDR-L2；和(c)包含SEQ ID NO：134的氨基酸序列的CDR-L3。在 一个实施方案中，该抗体包含(a)包含SEQ ID NO：132的氨基酸序列的CDR-L1；(b)包含SEQ ID NO：133的氨基酸序列的CDR-L2；和(c)包含SEQ ID NO：134的氨基酸序列的CDR-L3。
在另一个方面，本发明的抗体包含(a)包含至少一种，至少两种，或所有三种选自下述的VH CDR序列的VH域：(i)包含SEQ ID NO：129的氨基酸序列的CDR-H1，(ii)包含SEQ ID NO：130的氨基酸序列的CDR-H2，和(iii)包含选自SEQ ID NO：131的氨基酸序列的CDR-H3；和(b)包含至少一种，至少两种，或所有三种选自下述的VL CDR序列的VL域：(i)包含SEQ ID NO：132的氨基酸序列的CDR-L1，(ii)包含SEQ ID NO：133的氨基酸序列的CDR-L2，和(c)包含SEQ ID NO：134的氨基酸序列的CDR-L3。
在另一个方面，本发明提供一种抗体，其包含(a)包含SEQ ID NO：129的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：130的氨基酸序列的CDR-H2；(c)包含SEQ ID NO：131的氨基酸序列的CDR-H3；(d)包含SEQ ID NO：132的氨基酸序列的CDR-L1；(e)包含SEQ ID NO：133的氨基酸序列的CDR-L2；和(f)包含选自SEQ ID NO：134的氨基酸序列的CDR-L3。
在任何上述实施方案中，抗RSV抗体是人或人源化的。在一个实施方案中，抗RSV抗体包含如任何上述实施方案中的CDR，且进一步包含受体人框架，例如人免疫球蛋白框架或人共有框架。
在另一个方面，抗RSV抗体包含与SEQ ID NO：135的氨基酸序列具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，99％，或100％序列同一性的重链可变域(VH)序列。在某些实施方案中，具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，或99％同一性的VH序列相对于参照序列含有替代(例如保守替代)，***，或删除，但是包含该序列的抗RSV抗体保留结合RSV的能力。在某些实施方案中，在SEQ ID NO：135中替代，***和/或删除总共1至10个氨基酸。在某些实施方案中，替代，***，或删除在CDR以外的区域中(即在FR中)发生。任选地，该抗RSV抗体包含SEQ ID NO：135中的VH序列，包括该序列的翻译后修饰。在一个特定实施方案中，该VH包含一种，两种或三种选自下述的CDR：(a)包含SEQ ID NO：129的氨基酸序列的CDR-H1，(b)包含SEQ ID NO：130的氨基酸序列的CDR-H2，和(c)包含SEQ ID NO：131的氨基酸序列的CDR-H3。
在另一个方面，提供了一种抗RSV抗体，其中该抗体包含与SEQ ID NO：136的氨基酸序列具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，99％，或100％序列同一性的轻链可变域(VL)。在某些实施方案中，具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，或99％同一性的VL序列相对于参照序列含有替代(例如保守替代)，***，或删除，但是包含该序列的抗RSV抗体保留结合RSV的能力。在某些实施方案中，在SEQ ID NO：136中替代，***和/或删除总共1至10个氨基酸。在某些实施方案中，该替代，***，或删除在CDR以外的区域中(即在FR中)发生。任选地，该抗RSV抗体包含SEQ ID NO：136中的VL序列，包括该序列的翻译后修饰。在一个特定实施方案中，该VL包含一种，两种或三种选自下述的CDR：(a)包含SEQ ID NO：132的氨基酸序列的CDR-L1；(b)包含SEQ ID NO：133的氨基酸序列的CDR-L2；和(c)包含SEQ ID NO：134的氨基酸序列的CDR-L3。
在另一个方面，提供了一种抗RSV抗体，其中该抗体包含如任何上文提供的实施方案中的VH，和如任何上文提供的实施方案中的VL。在一个实施方案中，该抗体包含分别在SEQ ID NO：135和SEQ ID NO：136中的VH和VL序列，包括那些序列的翻译后修饰。
在又一个方面，本发明提供与本文中提供的抗RSV抗体结合相同表位的抗体。例如，在某些实施方案中，提供了与包含SEQ ID NO：135的VH序列和SEQ ID NO：136的VL序列的抗RSV抗体结合相同表位的抗体。
在一个方面，本发明提供一种抗RSV抗体，其包含至少一种，两种，三种，四种，五种，或六种选自下述的CDR：(a)包含SEQ ID NO：137的氨基酸序列的CDR-H1；(b)包含 SEQ ID NO：138的氨基酸序列的CDR-H2；(c)包含SEQ ID NO：139的氨基酸序列的CDR-H3；(d)包含SEQ ID NO：140的氨基酸序列的CDR-L1；(e)包含SEQ ID NO：141的氨基酸序列的CDR-L2；和(f)包含SEQ ID NO：142的氨基酸序列的CDR-L3。
在一个方面，本发明提供一种抗体，其包含至少一种，至少两种，或所有三种选自下述的VH CDR序列：(a)包含SEQ ID NO：137的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：138的氨基酸序列的CDR-H2；和(c)包含SEQ ID NO：139的氨基酸序列的CDR-H3。在一个实施方案中，该抗体包含包含SEQ ID NO：139的氨基酸序列的CDR-H3。在另一个实施方案中，该抗体包含包含SEQ ID NO：139的氨基酸序列的CDR-H3和包含SEQ ID NO：142的氨基酸序列的CDR-L3。在又一个实施方案中，该抗体包含包含SEQ ID NO：139的氨基酸序列的CDR-H3，包含SEQ ID NO：142的氨基酸序列的CDR-L3，和包含SEQ ID NO：138的氨基酸序列的CDR-H2。在又一个实施方案中，该抗体包含(a)包含SEQ ID NO：137的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：138的氨基酸序列的CDR-H2；和(c)包含SEQ ID NO：139的氨基酸序列的CDR-H3。
在另一个方面，本发明提供一种抗体，其包含至少一种，至少两种，或所有三种选自下述的VL CDR序列：(a)包含SEQ ID NO：140的氨基酸序列的CDR-L1；(b)包含SEQ ID NO：141的氨基酸序列的CDR-L2；和(c)包含SEQ ID NO：142的氨基酸序列的CDR-L3。在一个实施方案中，该抗体包含(a)包含SEQ ID NO：140的氨基酸序列的CDR-L1；(b)包含SEQ ID NO：141的氨基酸序列的CDR-L2；和(c)包含SEQ ID NO：142的氨基酸序列的CDR-L3。
在另一个方面，本发明的抗体包含(a)包含至少一种，至少两种，或所有三种选自下述的VH CDR序列的VH域：(i)包含SEQ ID NO：137的氨基酸序列的CDR-H1，(ii)包含SEQ ID NO：138的氨基酸序列的CDR-H2，和(iii)包含选自SEQ ID NO：139的氨基酸序列的CDR-H3；和(b)包含至少一种，至少两种，或所有三种选自下述的VL CDR序列的VL域：(i)包含SEQ ID NO：140的氨基酸序列的CDR-L1，(ii)包含SEQ ID NO：141的氨基酸序列的CDR-L2，和(c)包含SEQ ID NO：142的氨基酸序列的CDR-L3。
在另一个方面，本发明提供一种抗体，其包含(a)包含SEQ ID NO：137的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：138的氨基酸序列的CDR-H2；(c)包含SEQ ID NO：139的氨基酸序列的CDR-H3；(d)包含SEQ ID NO：140的氨基酸序列的CDR-L1；(e)包含SEQ ID NO：141的氨基酸序列的CDR-L2；和(f)包含选自SEQ ID NO：142的氨基酸序列的CDR-L3。
在任何上述实施方案中，抗RSV抗体是人或人源化的。在一个实施方案中，抗RSV抗体包含如任何上述实施方案中的CDR，且进一步包含受体人框架，例如人免疫球蛋白框架或人共有框架。
在另一个方面，抗RSV抗体包含与SEQ ID NO：143的氨基酸序列具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，99％，或100％序列同一性的重链可变域(VH)序列。在某些实施方案中，具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，或99％同一性的VH序列相对于参照序列含有替代(例如保守替代)，***，或删除，但是包含该序列的抗RSV抗体保留结合RSV的能力。在某些实施方案中，在SEQ ID NO：143中替代，***和/或删除总共1至10个氨基酸。在某些实施方案中，替代，***，或删除在CDR以外的区域中(即在FR中)发生。任选地，该抗RSV抗体包含SEQ ID NO：143中的VH序列，包括该序列的翻译后修饰。在一个特定实施方案中，该VH包含一种，两种或三种选自下述的CDR：(a)包含SEQ ID NO：137的氨基酸序列的CDR-H1，(b)包含SEQ ID NO：138的氨基酸序列的CDR-H2，和(c)包含SEQ ID NO：139的氨基酸序列的CDR-H3。
在另一个方面，提供了一种抗RSV抗体，其中该抗体包含与SEQ ID NO：144的氨基酸序列具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，99％，或100％序列同一 性的轻链可变域·(VL)。在某些实施方案中，具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，或99％同一性的VL序列相对于参照序列含有替代(例如保守替代)，***，或删除，但是包含该序列的抗RSV抗体保留结合RSV的能力。在某些实施方案中，在SEQ ID NO：144中替代，***和/或删除总共1至10个氨基酸。在某些实施方案中，该替代，***，或删除在CDR以外的区域中(即在FR中)发生。任选地，该抗RSV抗体包含SEQ ID NO：144中的VL序列，包括该序列的翻译后修饰。在一个特定实施方案中，该VL包含一种，两种或三种选自下述的CDR：(a)包含SEQ ID NO：140的氨基酸序列的CDR-L1；(b)包含SEQ ID NO：141的氨基酸序列的CDR-L2；和(c)包含SEQ ID NO：142的氨基酸序列的CDR-L3。
在另一个方面，提供了一种抗RSV抗体，其中该抗体包含如任何上文提供的实施方案中的VH，和如任何上文提供的实施方案中的VL。在一个实施方案中，该抗体包含分别在SEQ ID NO：143和SEQ ID NO：144中的VH和VL序列，包括那些序列的翻译后修饰。
在又一个方面，本发明提供与本文中提供的抗RSV抗体结合相同表位的抗体。例如，在某些实施方案中，提供了与包含SEQ ID NO：143的VH序列和SEQ ID NO：144的VL序列的抗RSV抗体结合相同表位的抗体。
在一个方面，本发明提供一种抗RSV抗体，其包含至少一种，两种，三种，四种，五种，或六种选自下述的CDR：(a)包含SEQ ID NO：145的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：146的氨基酸序列的CDR-H2；(c)包含SEQ ID NO：147的氨基酸序列的CDR-H3；(d)包含SEQ ID NO：148的氨基酸序列的CDR-L1；(e)包含SEQ ID NO：149的氨基酸序列的CDR-L2；和(f)包含SEQ ID NO：150的氨基酸序列的CDR-L3。
在一个方面，本发明提供一种抗体，其包含至少一种，至少两种，或所有三种选自下述的VH CDR序列：(a)包含SEQ ID NO：145的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：146的氨基酸序列的CDR-H2；和(c)包含SEQ ID NO：147的氨基酸序列的CDR-H3。在一个实施方案中，该抗体包含包含SEQ ID NO：147的氨基酸序列的CDR-H3。在另一个实施方案中，该抗体包含包含SEQ ID NO：147的氨基酸序列的CDR-H3和包含SEQ ID NO：150的氨基酸序列的CDR-L3。在又一个实施方案中，该抗体包含包含SEQ ID NO：147的氨基酸序列的CDR-H3，包含SEQ ID NO：150的氨基酸序列的CDR-L3，和包含SEQ ID NO：146的氨基酸序列的CDR-H2。在又一个实施方案中，该抗体包含(a)包含SEQ ID NO：145的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：146的氨基酸序列的CDR-H2；和(c)包含SEQ ID NO：147的氨基酸序列的CDR-H3。
在另一个方面，本发明提供一种抗体，其包含至少一种，至少两种，或所有三种选自下述的VL CDR序列：(a)包含SEQ ID NO：148的氨基酸序列的CDR-L1；(b)包含SEQ ID NO：149的氨基酸序列的CDR-L2；和(c)包含SEQ ID NO：150的氨基酸序列的CDR-L3。在一个实施方案中，该抗体包含(a)包含SEQ ID NO：148的氨基酸序列的CDR-L1；(b)包含SEQ ID NO：149的氨基酸序列的CDR-L2；和(c)包含SEQ ID NO：150的氨基酸序列的CDR-L3。
在另一个方面，本发明的抗体包含(a)包含至少一种，至少两种，或所有三种选自下述的VH CDR序列的VH域：(i)包含SEQ ID NO：145的氨基酸序列的CDR-H1，(ii)包含SEQ ID NO：146的氨基酸序列的CDR-H2，和(iii)包含选自SEQ ID NO：147的氨基酸序列的CDR-H3；和(b)包含至少一种，至少两种，或所有三种选自下述的VL CDR序列的VL域：(i)包含SEQ ID NO：148的氨基酸序列的CDR-L1，(ii)包含SEQ ID NO：149的氨基酸序列的CDR-L2，和(c)包含SEQ ID NO：150的氨基酸序列的CDR-L3。
在另一个方面，本发明提供一种抗体，其包含(a)包含SEQ ID NO：145的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：146的氨基酸序列的CDR-H2；(c)包含SEQ ID NO：147的氨基酸序列的CDR-H3；(d)包含SEQ ID NO：148的氨基酸序列的CDR-L1；(e)包含SEQ ID NO：149的氨基酸序列的CDR-L2；和(f)包含选自SEQ ID NO：150的氨基酸序列的 CDR-L3。
在任何上述实施方案中，抗RSV抗体是人或人源化的。在一个实施方案中，抗RSV抗体包含如任何上述实施方案中的CDR，且进一步包含受体人框架，例如人免疫球蛋白框架或人共有框架。
在另一个方面，抗RSV抗体包含与SEQ ID NO：151的氨基酸序列具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，99％，或100％序列同一性的重链可变域(VH)序列。在某些实施方案中，具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，或99％同一性的VH序列相对于参照序列含有替代(例如保守替代)，***，或删除，但是包含该序列的抗RSV抗体保留结合RSV的能力。在某些实施方案中，在SEQ ID NO：151中替代，***和/或删除总共1至10个氨基酸。在某些实施方案中，替代，***，或删除在CDR以外的区域中(即在FR中)发生。任选地，该抗RSV抗体包含SEQ ID NO：151中的VH序列，包括该序列的翻译后修饰。在一个特定实施方案中，该VH包含一种，两种或三种选自下述的CDR：(a)包含SEQ ID NO：145的氨基酸序列的CDR-H1，(b)包含SEQ ID NO：146的氨基酸序列的CDR-H2，和(c)包含SEQ ID NO：147的氨基酸序列的CDR-H3。
在另一个方面，提供了一种抗RSV抗体，其中该抗体包含与SEQ ID NO：152的氨基酸序列具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，99％，或100％序列同一性的轻链可变域·(VL)。在某些实施方案中，具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，或99％同一性的VL序列相对于参照序列含有替代(例如保守替代)，***，或删除，但是包含该序列的抗RSV抗体保留结合RSV的能力。在某些实施方案中，在SEQ ID NO：152中替代，***和/或删除总共1至10个氨基酸。在某些实施方案中，该替代，***，或删除在CDR以外的区域中(即在FR中)发生。任选地，该抗RSV抗体包含SEQ ID NO：152中的VL序列，包括该序列的翻译后修饰。在一个特定实施方案中，该VL包含一种，两种或三种选自下述的CDR：(a)包含SEQ ID NO：148的氨基酸序列的CDR-L1；(b)包含SEQ ID NO：149的氨基酸序列的CDR-L2；和(c)包含SEQ ID NO：150的氨基酸序列的CDR-L3。
在另一个方面，提供了一种抗RSV抗体，其中该抗体包含如任何上文提供的实施方案中的VH，和如任何上文提供的实施方案中的VL。在一个实施方案中，该抗体包含分别在SEQ ID NO：151和SEQ ID NO：152中的VH和VL序列，包括那些序列的翻译后修饰。
在又一个方面，本发明提供与本文中提供的抗RSV抗体结合相同表位的抗体。例如，在某些实施方案中，提供了与包含SEQ ID NO：151的VH序列和SEQ ID NO：152的VL序列的抗RSV抗体结合相同表位的抗体。
在一个方面，本发明提供一种抗RSV抗体，其包含至少一种，两种，三种，四种，五种，或六种选自下述的CDR：(a)包含SEQ ID NO：153的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：154的氨基酸序列的CDR-H2；(c)包含SEQ ID NO：155的氨基酸序列的CDR-H3；(d)包含SEQ ID NO：156的氨基酸序列的CDR-L1；(e)包含SEQ ID NO：157的氨基酸序列的CDR-L2；和(f)包含SEQ ID NO：158的氨基酸序列的CDR-L3。
在一个方面，本发明提供一种抗体，其包含至少一种，至少两种，或所有三种选自下述的VH CDR序列：(a)包含SEQ ID NO：153的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：154的氨基酸序列的CDR-H2；和(c)包含SEQ ID NO：155的氨基酸序列的CDR-H3。在一个实施方案中，该抗体包含包含SEQ ID NO：155的氨基酸序列的CDR-H3。在另一个实施方案中，该抗体包含包含SEQ ID NO：155的氨基酸序列的CDR-H3和包含SEQ ID NO：158的氨基酸序列的CDR-L3。在又一个实施方案中，该抗体包含包含SEQ ID NO：155的氨基酸序列的CDR-H3，包含SEQ ID NO：158的氨基酸序列的CDR-L3，和包含SEQ ID NO：154的氨基酸序列的CDR-H2。在又一个实施方案中，该抗体包含(a)包含SEQ ID NO：153的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：154的氨基酸序列的CDR-H2；和(c)包含SEQ ID NO：155的氨基酸序列的CDR-H3。
在另一个方面，本发明提供一种抗体，其包含至少一种，至少两种，或所有三种选自下述的VL CDR序列：(a)包含SEQ ID NO：156的氨基酸序列的CDR-L1；(b)包含SEQ ID NO：157的氨基酸序列的CDR-L2；和(c)包含SEQ ID NO：158的氨基酸序列的CDR-L3。在一个实施方案中，该抗体包含(a)包含SEQ ID NO：156的氨基酸序列的CDR-L1；(b)包含SEQ ID NO：157的氨基酸序列的CDR-L2；和(c)包含SEQ ID NO：158的氨基酸序列的CDR-L3。
在另一个方面，本发明的抗体包含(a)包含至少一种，至少两种，或所有三种选自下述的VH CDR序列的VH域：(i)包含SEQ ID NO：153的氨基酸序列的CDR-H1，(ii)包含SEQ ID NO：154的氨基酸序列的CDR-H2，和(iii)包含选自SEQ ID NO：155的氨基酸序列的CDR-H3；和(b)包含至少一种，至少两种，或所有三种选自下述的VL CDR序列的VL域：(i)包含SEQ ID NO：156的氨基酸序列的CDR-L1，(ii)包含SEQ ID NO：157的氨基酸序列的CDR-L2，和(c)包含SEQ ID NO：158的氨基酸序列的CDR-L3。
在另一个方面，本发明提供一种抗体，其包含(a)包含SEQ ID NO：153的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：154的氨基酸序列的CDR-H2；(c)包含SEQ ID NO：155的氨基酸序列的CDR-H3；(d)包含SEQ ID NO：156的氨基酸序列的CDR-L1；(e)包含SEQ ID NO：157的氨基酸序列的CDR-L2；和(f)包含选自SEQ ID NO：158的氨基酸序列的CDR-L3。
在任何上述实施方案中，抗RSV抗体是人或人源化的。在一个实施方案中，抗RSV抗体包含如任何上述实施方案中的CDR，且进一步包含受体人框架，例如人免疫球蛋白框架或人共有框架。
在另一个方面，抗RSV抗体包含与SEQ ID NO：159的氨基酸序列具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，99％，或100％序列同一性的重链可变域(VH)序列。在某些实施方案中，具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，或99％同一性的VH序列相对于参照序列含有替代(例如保守替代)，***，或删除，但是包含该序列的抗RSV抗体保留结合RSV的能力。在某些实施方案中，在SEQ ID NO：159中替代，***和/或删除总共1至10个氨基酸。在某些实施方案中，替代，***，或删除在CDR以外的区域中(即在FR中)发生。任选地，该抗RSV抗体包含SEQ ID NO：159中的VH序列，包括该序列的翻译后修饰。在一个特定实施方案中，该VH包含一种，两种或三种选自下述的CDR：(a)包含SEQ ID NO：153的氨基酸序列的CDR-H1，(b)包含SEQ ID NO：154的氨基酸序列的CDR-H2，和(c)包含SEQ ID NO：155的氨基酸序列的CDR-H3。
在另一个方面，提供了一种抗RSV抗体，其中该抗体包含与SEQ ID NO：160的氨基酸序列具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，99％，或100％序列同一性的轻链可变域·(VL)。在某些实施方案中，具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，或99％同一性的VL序列相对于参照序列含有替代(例如保守替代)，***，或删除，但是包含该序列的抗RSV抗体保留结合RSV的能力。在某些实施方案中，在SEQ ID NO：160中替代，***和/或删除总共1至10个氨基酸。在某些实施方案中，该替代，***，或删除在CDR以外的区域中(即在FR中)发生。任选地，该抗RSV抗体包含SEQ ID NO：160中的VL序列，包括该序列的翻译后修饰。在一个特定实施方案中，该VL包含一种，两种或三种选自下述的CDR：(a)包含SEQ ID NO：156的氨基酸序列的CDR-L1；(b)包含SEQ ID NO：157的氨基酸序列的CDR-L2；和(c)包含SEQ ID NO：158的氨基酸序列的CDR-L3。
在另一个方面，提供了一种抗RSV抗体，其中该抗体包含如任何上文提供的实施方案中的VH，和如任何上文提供的实施方案中的VL。在一个实施方案中，该抗体包含分别在SEQ ID NO：159和SEQ ID NO：160中的VH和VL序列，包括那些序列的翻译后修饰。
在又一个方面，本发明提供与本文中提供的抗RSV抗体结合相同表位的抗体。例如，在某些实施方案中，提供了与包含SEQ ID NO：159的VH序列和SEQ ID NO：160的VL序 列的抗RSV抗体结合相同表位的抗体。
在一个方面，本发明提供一种抗RSV抗体，其包含至少一种，两种，三种，四种，五种，或六种选自下述的CDR：(a)包含SEQ ID NO：161的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：162的氨基酸序列的CDR-H2；(c)包含SEQ ID NO：163的氨基酸序列的CDR-H3；(d)包含SEQ ID NO：164的氨基酸序列的CDR-L1；(e)包含SEQ ID NO：165的氨基酸序列的CDR-L2；和(f)包含SEQ ID NO：166的氨基酸序列的CDR-L3。
在一个方面，本发明提供一种抗体，其包含至少一种，至少两种，或所有三种选自下述的VH CDR序列：(a)包含SEQ ID NO：161的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：162的氨基酸序列的CDR-H2；和(c)包含SEQ ID NO：163的氨基酸序列的CDR-H3。在一个实施方案中，该抗体包含包含SEQ ID NO：163的氨基酸序列的CDR-H3。在另一个实施方案中，该抗体包含包含SEQ ID NO：163的氨基酸序列的CDR-H3和包含SEQ ID NO：166的氨基酸序列的CDR-L3。在又一个实施方案中，该抗体包含包含SEQ ID NO：163的氨基酸序列的CDR-H3，包含SEQ ID NO：166的氨基酸序列的CDR-L3，和包含SEQ ID NO：162的氨基酸序列的CDR-H2。在又一个实施方案中，该抗体包含(a)包含SEQ ID NO：161的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：162的氨基酸序列的CDR-H2；和(c)包含SEQ ID NO：163的氨基酸序列的CDR-H3。
在另一个方面，本发明提供一种抗体，其包含至少一种，至少两种，或所有三种选自下述的VL CDR序列：(a)包含SEQ ID NO：164的氨基酸序列的CDR-L1；(b)包含SEQ ID NO：165的氨基酸序列的CDR-L2；和(c)包含SEQ ID NO：166的氨基酸序列的CDR-L3。在一个实施方案中，该抗体包含(a)包含SEQ ID NO：164的氨基酸序列的CDR-L1；(b)包含SEQ ID NO：165的氨基酸序列的CDR-L2；和(c)包含SEQ ID NO：166的氨基酸序列的CDR-L3。
在另一个方面，本发明的抗体包含(a)包含至少一种，至少两种，或所有三种选自下述的VH CDR序列的VH域：(i)包含SEQ ID NO：161的氨基酸序列的CDR-H1，(ii)包含SEQ ID NO：162的氨基酸序列的CDR-H2，和(iii)包含选自SEQ ID NO：163的氨基酸序列的CDR-H3；和(b)包含至少一种，至少两种，或所有三种选自下述的VL CDR序列的VL域：(i)包含SEQ ID NO：164的氨基酸序列的CDR-L1，(ii)包含SEQ ID NO：165的氨基酸序列的CDR-L2，和(c)包含SEQ ID NO：166的氨基酸序列的CDR-L3。
在另一个方面，本发明提供一种抗体，其包含(a)包含SEQ ID NO：161的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：162的氨基酸序列的CDR-H2；(c)包含SEQ ID NO：163的氨基酸序列的CDR-H3；(d)包含SEQ ID NO：164的氨基酸序列的CDR-L1；(e)包含SEQ ID NO：165的氨基酸序列的CDR-L2；和(f)包含选自SEQ ID NO：166的氨基酸序列的CDR-L3。
在任何上述实施方案中，抗RSV抗体是人或人源化的。在一个实施方案中，抗RSV抗体包含如任何上述实施方案中的CDR，且进一步包含受体人框架，例如人免疫球蛋白框架或人共有框架。
在另一个方面，抗RSV抗体包含与SEQ ID NO：167的氨基酸序列具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，99％，或100％序列同一性的重链可变域(VH)序列。在某些实施方案中，具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，或99％同一性的VH序列相对于参照序列含有替代(例如保守替代)，***，或删除，但是包含该序列的抗RSV抗体保留结合RSV的能力。在某些实施方案中，在SEQ ID NO：167中替代，***和/或删除总共1至10个氨基酸。在某些实施方案中，替代，***，或删除在CDR以外的区域中(即在FR中)发生。任选地，该抗RSV抗体包含SEQ ID NO：167中的VH序列，包括该序列的翻译后修饰。在一个特定实施方案中，该VH包含一种，两种或三种选自下述的CDR：(a)包含SEQ ID NO：161的氨基酸序列的CDR-H1，(b)包含SEQ ID NO：162的氨基酸 序列的CDR-H2，和(c)包含SEQ ID NO：163的氨基酸序列的CDR-H3。
在另一个方面，提供了一种抗RSV抗体，其中该抗体包含与SEQ ID NO：168的氨基酸序列具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，99％，或100％序列同一性的轻链可变域·(VL)。在某些实施方案中，具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，或99％同一性的VL序列相对于参照序列含有替代(例如保守替代)，***，或删除，但是包含该序列的抗RSV抗体保留结合RSV的能力。在某些实施方案中，在SEQ ID NO：168中替代，***和/或删除总共1至10个氨基酸。在某些实施方案中，该替代，***，或删除在CDR以外的区域中(即在FR中)发生。任选地，该抗RSV抗体包含SEQ ID NO：168中的VL序列，包括该序列的翻译后修饰。在一个特定实施方案中，该VL包含一种，两种或三种选自下述的CDR：(a)包含SEQ ID NO：164的氨基酸序列的CDR-L1；(b)包含SEQ ID NO：165的氨基酸序列的CDR-L2；和(c)包含SEQ ID NO：166的氨基酸序列的CDR-L3。
在另一个方面，提供了一种抗RSV抗体，其中该抗体包含如任何上文提供的实施方案中的VH，和如任何上文提供的实施方案中的VL。在一个实施方案中，该抗体包含分别在SEQ ID NO：167和SEQ ID NO：168中的VH和VL序列，包括那些序列的翻译后修饰。
在又一个方面，本发明提供与本文中提供的抗RSV抗体结合相同表位的抗体。例如，在某些实施方案中，提供了与包含SEQ ID NO：167的VH序列和SEQ ID NO：168的VL序列的抗RSV抗体结合相同表位的抗体。
在一个方面，本发明提供一种抗RSV抗体，其包含至少一种，两种，三种，四种，五种，或六种选自下述的CDR：(a)包含SEQ ID NO：169的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：170的氨基酸序列的CDR-H2；(c)包含SEQ ID NO：171的氨基酸序列的CDR-H3；(d)包含SEQ ID NO：172的氨基酸序列的CDR-L1；(e)包含SEQ ID NO：173的氨基酸序列的CDR-L2；和(f)包含SEQ ID NO：174的氨基酸序列的CDR-L3。
在一个方面，本发明提供一种抗体，其包含至少一种，至少两种，或所有三种选自下述的VH CDR序列：(a)包含SEQ ID NO：169的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：170的氨基酸序列的CDR-H2；和(c)包含SEQ ID NO：171的氨基酸序列的CDR-H3。在一个实施方案中，该抗体包含包含SEQ ID NO：171的氨基酸序列的CDR-H3。在另一个实施方案中，该抗体包含包含SEQ ID NO：171的氨基酸序列的CDR-H3和包含SEQ ID NO：174的氨基酸序列的CDR-L3。在又一个实施方案中，该抗体包含包含SEQ ID NO：171的氨基酸序列的CDR-H3，包含SEQ ID NO：174的氨基酸序列的CDR-L3，和包含SEQ ID NO：170的氨基酸序列的CDR-H2。在又一个实施方案中，该抗体包含(a)包含SEQ ID NO：169的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：170的氨基酸序列的CDR-H2；和(c)包含SEQ ID NO：171的氨基酸序列的CDR-H3。
在另一个方面，本发明提供一种抗体，其包含至少一种，至少两种，或所有三种选自下述的VL CDR序列：(a)包含SEQ ID NO：172的氨基酸序列的CDR-L1；(b)包含SEQ ID NO：173的氨基酸序列的CDR-L2；和(c)包含SEQ ID NO：174的氨基酸序列的CDR-L3。在一个实施方案中，该抗体包含(a)包含SEQ ID NO：172的氨基酸序列的CDR-L1；(b)包含SEQ ID NO：173的氨基酸序列的CDR-L2；和(c)包含SEQ ID NO：174的氨基酸序列的CDR-L3。
在另一个方面，本发明的抗体包含(a)包含至少一种，至少两种，或所有三种选自下述的VH CDR序列的VH域：(i)包含SEQ ID NO：169的氨基酸序列的CDR-H1，(ii)包含SEQ ID NO：170的氨基酸序列的CDR-H2，和(iii)包含选自SEQ ID NO：171的氨基酸序列的CDR-H3；和(b)包含至少一种，至少两种，或所有三种选自下述的VL CDR序列的VL域：(i)包含SEQ ID NO：172的氨基酸序列的CDR-L1，(ii)包含SEQ ID NO：173的氨基酸序列的CDR-L2，和(c)包含SEQ ID NO：174的氨基酸序列的CDR-L3。
在另一个方面，本发明提供一种抗体，其包含(a)包含SEQ ID NO：169的氨基酸序列 的CDR-H1；(b)包含SEQ ID NO：170的氨基酸序列的CDR-H2；(c)包含SEQ ID NO：171的氨基酸序列的CDR-H3；(d)包含SEQ ID NO：172的氨基酸序列的CDR-L1；(e)包含SEQ ID NO：173的氨基酸序列的CDR-L2；和(f)包含选自SEQ ID NO：174的氨基酸序列的CDR-L3。
在任何上述实施方案中，抗RSV抗体是人或人源化的。在一个实施方案中，抗RSV抗体包含如任何上述实施方案中的CDR，且进一步包含受体人框架，例如人免疫球蛋白框架或人共有框架。
在另一个方面，抗RSV抗体包含与SEQ ID NO：175的氨基酸序列具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，99％，或100％序列同一性的重链可变域(VH)序列。在某些实施方案中，具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，或99％同一性的VH序列相对于参照序列含有替代(例如保守替代)，***，或删除，但是包含该序列的抗RSV抗体保留结合RSV的能力。在某些实施方案中，在SEQ ID NO：175中替代，***和/或删除总共1至10个氨基酸。在某些实施方案中，替代，***，或删除在CDR以外的区域中(即在FR中)发生。任选地，该抗RSV抗体包含SEQ ID NO：175中的VH序列，包括该序列的翻译后修饰。在一个特定实施方案中，该VH包含一种，两种或三种选自下述的CDR：(a)包含SEQ ID NO：169的氨基酸序列的CDR-H1，(b)包含SEQ ID NO：170的氨基酸序列的CDR-H2，和(c)包含SEQ ID NO：171的氨基酸序列的CDR-H3。
在另一个方面，提供了一种抗RSV抗体，其中该抗体包含与SEQ ID NO：176的氨基酸序列具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，99％，或100％序列同一性的轻链可变域·(VL)。在某些实施方案中，具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，或99％同一性的VL序列相对于参照序列含有替代(例如保守替代)，***，或删除，但是包含该序列的抗RSV抗体保留结合RSV的能力。在某些实施方案中，在SEQ ID NO：176中替代，***和/或删除总共1至10个氨基酸。在某些实施方案中，该替代，***，或删除在CDR以外的区域中(即在FR中)发生。任选地，该抗RSV抗体包含SEQ ID NO：176中的VL序列，包括该序列的翻译后修饰。在一个特定实施方案中，该VL包含一种，两种或三种选自下述的CDR：(a)包含SEQ ID NO：72的氨基酸序列的CDR-L1；(b)包含SEQ ID NO：173的氨基酸序列的CDR-L2；和(c)包含SEQ ID NO：174的氨基酸序列的CDR-L3。
在另一个方面，提供了一种抗RSV抗体，其中该抗体包含如任何上文提供的实施方案中的VH，和如任何上文提供的实施方案中的VL。在一个实施方案中，该抗体包含分别在SEQ ID NO：175和SEQ ID NO：176中的VH和VL序列，包括那些序列的翻译后修饰。
在又一个方面，本发明提供与本文中提供的抗RSV抗体结合相同表位的抗体。例如，在某些实施方案中，提供了与包含SEQ ID NO：175的VH序列和SEQ ID NO：176的VL序列的抗RSV抗体结合相同表位的抗体。
在一个方面，本发明提供一种抗RSV抗体，其包含至少一种，两种，三种，四种，五种，或六种选自下述的CDR：(a)包含SEQ ID NO：177的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：178的氨基酸序列的CDR-H2；(c)包含SEQ ID NO：179的氨基酸序列的CDR-H3；(d)包含SEQ ID NO：180的氨基酸序列的CDR-L1；(e)包含SEQ ID NO：181的氨基酸序列的CDR-L2；和(f)包含SEQ ID NO：182的氨基酸序列的CDR-L3。
在一个方面，本发明提供一种抗体，其包含至少一种，至少两种，或所有三种选自下述的VH CDR序列：(a)包含SEQ ID NO：177的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：178的氨基酸序列的CDR-H2；和(c)包含SEQ ID NO：179的氨基酸序列的CDR-H3。在一个实施方案中，该抗体包含包含SEQ ID NO：179的氨基酸序列的CDR-H3。在另一个实施方案中，该抗体包含包含SEQ ID NO：179的氨基酸序列的CDR-H3和包含SEQ ID NO：182的氨基酸序列的CDR-L3。在又一个实施方案中，该抗体包含包含SEQ ID NO：179的氨基酸序列的CDR-H3，包含SEQ ID NO：182的氨基酸序列的CDR-L3，和包含SEQ ID NO：178 的氨基酸序列的CDR-H2。在又一个实施方案中，该抗体包含(a)包含SEQ ID NO：177的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：178的氨基酸序列的CDR-H2；和(c)包含SEQ ID NO：179的氨基酸序列的CDR-H3。
在另一个方面，本发明提供一种抗体，其包含至少一种，至少两种，或所有三种选自下述的VL CDR序列：(a)包含SEQ ID NO：180的氨基酸序列的CDR-L1；(b)包含SEQ ID NO：181的氨基酸序列的CDR-L2；和(c)包含SEQ ID NO：182的氨基酸序列的CDR-L3。在一个实施方案中，该抗体包含(a)包含SEQ ID NO：180的氨基酸序列的CDR-L1；(b)包含SEQ ID NO：181的氨基酸序列的CDR-L2；和(c)包含SEQ ID NO：182的氨基酸序列的CDR-L3。
在另一个方面，本发明的抗体包含(a)包含至少一种，至少两种，或所有三种选自下述的VH CDR序列的VH域：(i)包含SEQ ID NO：177的氨基酸序列的CDR-H1，(ii)包含SEQ ID NO：178的氨基酸序列的CDR-H2，和(iii)包含选自SEQ ID NO：179的氨基酸序列的CDR-H3；和(b)包含至少一种，至少两种，或所有三种选自下述的VL CDR序列的VL域：(i)包含SEQ ID NO：180的氨基酸序列的CDR-L1，(ii)包含SEQ ID NO：181的氨基酸序列的CDR-L2，和(c)包含SEQ ID NO：182的氨基酸序列的CDR-L3。
在另一个方面，本发明提供一种抗体，其包含(a)包含SEQ ID NO：177的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：178的氨基酸序列的CDR-H2；(c)包含SEQ ID NO：179的氨基酸序列的CDR-H3；(d)包含SEQ ID NO：180的氨基酸序列的CDR-L1；(e)包含SEQ ID NO：181的氨基酸序列的CDR-L2；和(f)包含选自SEQ ID NO：182的氨基酸序列的CDR-L3。
在任何上述实施方案中，抗RSV抗体是人或人源化的。在一个实施方案中，抗RSV抗体包含如任何上述实施方案中的CDR，且进一步包含受体人框架，例如人免疫球蛋白框架或人共有框架。
在另一个方面，抗RSV抗体包含与SEQ ID NO：183的氨基酸序列具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，99％，或100％序列同一性的重链可变域(VH)序列。在某些实施方案中，具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，或99％同一性的VH序列相对于参照序列含有替代(例如保守替代)，***，或删除，但是包含该序列的抗RSV抗体保留结合RSV的能力。在某些实施方案中，在SEQ ID NO：183中替代，***和/或删除总共1至10个氨基酸。在某些实施方案中，替代，***，或删除在CDR以外的区域中(即在FR中)发生。任选地，该抗RSV抗体包含SEQ ID NO：183中的VH序列，包括该序列的翻译后修饰。在一个特定实施方案中，该VH包含一种，两种或三种选自下述的CDR：(a)包含SEQ ID NO：177的氨基酸序列的CDR-H1，(b)包含SEQ ID NO：178的氨基酸序列的CDR-H2，和(c)包含SEQ ID NO：179的氨基酸序列的CDR-H3。
在另一个方面，提供了一种抗RSV抗体，其中该抗体包含与SEQ ID NO：184的氨基酸序列具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，99％，或100％序列同一性的轻链可变域·(VL)。在某些实施方案中，具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，或99％同一性的VL序列相对于参照序列含有替代(例如保守替代)，***，或删除，但是包含该序列的抗RSV抗体保留结合RSV的能力。在某些实施方案中，在SEQ ID NO：184中替代，***和/或删除总共1至10个氨基酸。在某些实施方案中，该替代，***，或删除在CDR以外的区域中(即在FR中)发生。任选地，该抗RSV抗体包含SEQ ID NO：184中的VL序列，包括该序列的翻译后修饰。在一个特定实施方案中，该VL包含一种，两种或三种选自下述的CDR：(a)包含SEQ ID NO：180的氨基酸序列的CDR-L1；(b)包含SEQ ID NO：181的氨基酸序列的CDR-L2；和(c)包含SEQ ID NO：182的氨基酸序列的CDR-L3。
在另一个方面，提供了一种抗RSV抗体，其中该抗体包含如任何上文提供的实施方案中的VH，和如任何上文提供的实施方案中的VL。在一个实施方案中，该抗体包含分别 在SEQ ID NO：183和SEQ ID NO：184中的VH和VL序列，包括那些序列的翻译后修饰。
在又一个方面，本发明提供与本文中提供的抗RSV抗体结合相同表位的抗体。例如，在某些实施方案中，提供了与包含SEQ ID NO：183的VH序列和SEQ ID NO：184的VL序列的抗RSV抗体结合相同表位的抗体。
在一个方面，本发明提供一种抗RSV抗体，其包含至少一种，两种，三种，四种，五种，或六种选自下述的CDR：(a)包含SEQ ID NO：185的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：186的氨基酸序列的CDR-H2；(c)包含SEQ ID NO：187的氨基酸序列的CDR-H3；(d)包含SEQ ID NO：188的氨基酸序列的CDR-L1；(e)包含SEQ ID NO：189的氨基酸序列的CDR-L2；和(f)包含SEQ ID NO：190的氨基酸序列的CDR-L3。
在一个方面，本发明提供一种抗体，其包含至少一种，至少两种，或所有三种选自下述的VH CDR序列：(a)包含SEQ ID NO：185的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：186的氨基酸序列的CDR-H2；和(c)包含SEQ ID NO：187的氨基酸序列的CDR-H3。在一个实施方案中，该抗体包含包含SEQ ID NO：187的氨基酸序列的CDR-H3。在另一个实施方案中，该抗体包含包含SEQ ID NO：187的氨基酸序列的CDR-H3和包含SEQ ID NO：190的氨基酸序列的CDR-L3。在又一个实施方案中，该抗体包含包含SEQ ID NO：187的氨基酸序列的CDR-H3，包含SEQ ID NO：190的氨基酸序列的CDR-L3，和包含SEQ ID NO：186的氨基酸序列的CDR-H2。在又一个实施方案中，该抗体包含(a)包含SEQ ID NO：185的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：186的氨基酸序列的CDR-H2；和(c)包含SEQ ID NO：187的氨基酸序列的CDR-H3。
在另一个方面，本发明提供一种抗体，其包含至少一种，至少两种，或所有三种选自下述的VL CDR序列：(a)包含SEQ ID NO：188的氨基酸序列的CDR-L1；(b)包含SEQ ID NO：189的氨基酸序列的CDR-L2；和(c)包含SEQ ID NO：190的氨基酸序列的CDR-L3。在一个实施方案中，该抗体包含(a)包含SEQ ID NO：188的氨基酸序列的CDR-L1；(b)包含SEQ ID NO：189的氨基酸序列的CDR-L2；和(c)包含SEQ ID NO：190的氨基酸序列的CDR-L3。
在另一个方面，本发明的抗体包含(a)包含至少一种，至少两种，或所有三种选自下述的VH CDR序列的VH域：(i)包含SEQ ID NO：185的氨基酸序列的CDR-H1，(ii)包含SEQ ID NO：186的氨基酸序列的CDR-H2，和(iii)包含选自SEQ ID NO：187的氨基酸序列的CDR-H3；和(b)包含至少一种，至少两种，或所有三种选自下述的VL CDR序列的VL域：(i)包含SEQ ID NO：188的氨基酸序列的CDR-L1，(ii)包含SEQ ID NO：189的氨基酸序列的CDR-L2，和(c)包含SEQ ID NO：190的氨基酸序列的CDR-L3。
在另一个方面，本发明提供一种抗体，其包含(a)包含SEQ ID NO：185的氨基酸序列的CDR-H1；(b)包含SEQ ID NO：186的氨基酸序列的CDR-H2；(c)包含SEQ ID NO：187的氨基酸序列的CDR-H3；(d)包含SEQ ID NO：188的氨基酸序列的CDR-L1；(e)包含SEQ ID NO：189的氨基酸序列的CDR-L2；和(f)包含选自SEQ ID NO：190的氨基酸序列的CDR-L3。
在任何上述实施方案中，抗RSV抗体是人或人源化的。在一个实施方案中，抗RSV抗体包含如任何上述实施方案中的CDR，且进一步包含受体人框架，例如人免疫球蛋白框架或人共有框架。
在另一个方面，抗RSV抗体包含与SEQ ID NO：191的氨基酸序列具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，99％，或100％序列同一性的重链可变域(VH)序列。在某些实施方案中，具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，或99％同一性的VH序列相对于参照序列含有替代(例如保守替代)，***，或删除，但是包含该序列的抗RSV抗体保留结合RSV的能力。在某些实施方案中，在SEQ ID NO：191中替代，***和/或删除总共1至10个氨基酸。在某些实施方案中，替代，***，或删除在CDR以外的 区域中(即在FR中)发生。任选地，该抗RSV抗体包含SEQ ID NO：191中的VH序列，包括该序列的翻译后修饰。在一个特定实施方案中，该VH包含一种，两种或三种选自下述的CDR：(a)包含SEQ ID NO：185的氨基酸序列的CDR-H1，(b)包含SEQ ID NO：186的氨基酸序列的CDR-H2，和(c)包含SEQ ID NO：187的氨基酸序列的CDR-H3。
在另一个方面，提供了一种抗RSV抗体，其中该抗体包含与SEQ ID NO：192的氨基酸序列具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，99％，或100％序列同一性的轻链可变域·(VL)。在某些实施方案中，具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％，或99％同一性的VL序列相对于参照序列含有替代(例如保守替代)，***，或删除，但是包含该序列的抗RSV抗体保留结合RSV的能力。在某些实施方案中，在SEQ ID NO：192中替代，***和/或删除总共1至10个氨基酸。在某些实施方案中，该替代，***，或删除在CDR以外的区域中(即在FR中)发生。任选地，该抗RSV抗体包含SEQ ID NO：192中的VL序列，包括该序列的翻译后修饰。在一个特定实施方案中，该VL包含一种，两种或三种选自下述的CDR：(a)包含SEQ ID NO：188的氨基酸序列的CDR-L1；(b)包含SEQ ID NO：189的氨基酸序列的CDR-L2；和(c)包含SEQ ID NO：190的氨基酸序列的CDR-L3。
在另一个方面，提供了一种抗RSV抗体，其中该抗体包含如任何上文提供的实施方案中的VH，和如任何上文提供的实施方案中的VL。在一个实施方案中，该抗体包含分别在SEQ ID NO：191和SEQ ID NO：192中的VH和VL序列，包括那些序列的翻译后修饰。
在又一个方面，本发明提供与本文中提供的抗RSV抗体结合相同表位的抗体。例如，在某些实施方案中，提供了与包含SEQ ID NO：191的VH序列和SEQ ID NO：192的VL序列的抗RSV抗体结合相同表位的抗体。
在本发明的又一个方面，依照任何上述实施方案的抗RSV抗体是单克隆抗体，包括嵌合，人源化或人抗体。在一个实施方案中，抗RSV抗体是抗体片段，例如Fv，Fab，Fab’，xFab，scFv，双抗体，或F(ab’)2片段。在另一个实施方案中，该抗体是全长抗体，例如具有自人IgG1Fc区衍生的Fc区中的替代L234A，L235A和P329G(LALA-PG)(参见例如WO2012/130831 A1)。
在又一个方面，依照任何上述实施方案的抗RSV抗体可单一地或组合地并入下文1-7节中描述的任何特征：
1.抗体亲和力
在某些实施方案中，本文中提供的抗体具有≤1μM，≤100nM，≤10nM，≤1nM，≤0.1nM，≤0.01nM，或≤0.001nM的解离常数(Kd)(例如10-8M或更少，例如10-8M至10-13M，例如10-9M至10-13M)。
在一个实施方案中，Kd是通过放射性标记抗原结合测定法(RIA)来测量的。在一个实施方案中，用Fab型式的感兴趣抗体及其抗原实施RIA。例如，通过在存在未标记抗原的滴定系列的情况中用最小浓度的(125I)标记抗原平衡Fab，然后用抗Fab抗体包被板捕捉结合的抗原来测量Fab对抗原的溶液结合亲和力(见例如Chen等，J.Mol.Biol.293：865-881(1999))。为了建立测定法的条件，将多孔板(Thermo Scientific)用50mM碳酸钠(pH 9.6)中的5μg/ml捕捉用抗Fab抗体(Cappel Labs)包被过夜，随后用PBS中的2％(w/v)牛血清白蛋白于室温(约23℃)封闭2-5小时。在非吸附板(Nunc#269620)中，将100pM或26pM[125I]-抗原与连续稀释的感兴趣Fab(例如与Presta等，Cancer Res.57：4593-4599(1997)中抗VEGF抗体，Fab-12的评估一致)混合。然后将感兴趣的Fab温育过夜；然而，温育可持续更长时间(例如约65小时)以确保达到平衡。此后，将混合物转移至捕捉板，于室温温育(例如1小时)。然后除去溶液，并用PBS中的0.1％聚山梨酯20洗板8次。平板干燥后，加入150μl/孔闪烁液(MICROSCINT-20TM；Packard)，然后在TOPCOUNTTM伽马计数器(Packard).上对平板计数10分钟。选择各Fab给出小于或等于最大结合之20％的浓度用于竞争性结合测定法。
依照另一个实施方案，Kd是使用表面等离振子共振测定法测量的。例如，于25℃使用固定化抗原CM5芯片在约10个响应单位(RU)使用或(BIAcore，Inc.，Piscataway，NJ)实施测定法。在一个实施方案中，依照供应商的用法说明书用盐酸N-乙基-N’-(3-二甲氨基丙基)-碳二亚胺(EDC)和N-羟基琥珀酰亚胺(NHS)活化羧甲基化右旋糖苷生物传感器芯片(CM5，BIACORE，Inc.)。将抗原用10mM乙酸钠pH 4.8稀释至5μg/ml(约0.2μM)，然后以5μl/分钟的流速注射以获得约10个响应单位(RU)的偶联蛋白质。注入抗原后，注入1M乙醇胺以封闭未反应基团。为了进行动力学测量，于25℃以约25μl/分钟的流速注入在含0.05％聚山梨酯20(TWEEN-20TM)表面活性剂的PBS(PBST)中两倍连续稀释的Fab(0.78nM至500nM)。使用简单一对一朗格缪尔(Langmuir)结合模型(Evaluation Software version 3.2)通过同时拟合结合和解离传感图计算结合速率(kon)和解离速率(koff)。平衡解离常数(Kd)以比率koff/kon计算。见例如Chen等，J.Mol.Biol.293：865-881(1999)。如果根据上文表面等离振子共振测定法，结合速率超过106M-1S-1，那么结合速率可使用荧光淬灭技术来测定，即根据分光计诸如配备了断流装置的分光光度计(Aviv Instruments)或8000系列SLM-AMINCOTM分光光度计(ThermoSpectronic)中用搅拌比色杯的测量，在存在浓度渐增的抗原的情况中，测量PBS pH 7.2中20nM抗抗原抗体(Fab形式)于25℃的荧光发射强度(激发＝295nm；发射＝340nm，16nm带通)的升高或降低。
2.抗体片段
在某些实施方案中，本文中提供的抗体是抗体片段。术语“抗体片段”指除了完整抗体以外的分子，其包含完整抗体中保留特异性结合抗原的能力的一部分。抗体片段包括但不限于Fab，Fab’，Fab’SH，F(ab’)2，xFab，Fv，单链Fab(scFab)，单链可变片段(scFv)和单域抗体(dAb)。关于某些抗体片段的综述，见Holliger and Hudson，Nature Biotechnology 23：1126-1136(2005)。
在一个实施方案中，抗体片段是Fab，Fab’，Fab’SH，xFab，或F(ab’)2片段，特别是Fab片段。完整抗体的木瓜蛋白酶消化产生两个完全相同的抗原结合片段，称为“Fab”片段，其各自含有重和轻链可变域以及轻链的恒定域和重链的第一恒定域(CH1)。因此，术语“Fab片段”是指包含包括轻链的VL域和恒定域(CL)的轻链片段，和重链的VH域和第一恒定域(CH1)的抗体片段。术语“xFab片段”是指其中VH域与VL交换或者CH1域与CL域交换的Fab片段。Fab′片段因在重链CHl域的羧基末端增加了残基而与Fab片段有所不同，包括来自抗体铰链区的一个或多个半胱氨酸。Fab′-SH是其中恒定域的半胱氨酸残基具有游离巯基的Fab′片段。胃蛋白酶处理产生具有两个抗原结合位点(两个Fab片段)和Fc区的一部分的F(ab′)2片段。关于包含补救受体结合表位残基，并且具有延长的体内半衰期的Fab和F(ab’)2片段的讨论，见美国专利No.5,869,046。
在另一个实施方案中，抗体片段是双抗体，三抗体或四抗体。双抗体是具有两个抗原结合位点的抗体片段，其可以是二价的或双特异性的。见例如EP 404，097；WO1993/01161；Hudson等，Nat.Med.9：129-134(2003)；和Hollinger等，Proc.Natl.Acad.Sci.USA 90：6444-6448(1993)。三抗体和四抗体也记载于Hudson等，Nat.Med.9：129-134(2003)。
在又一个实施方案中，抗体片段是单链Fab片段。“单链Fab片段”或“scFab”是由抗体重链可变域(VH)，抗体恒定域1(CH1)，抗体轻链可变域(VL)，抗体轻链恒定域(CL)和接头组成的多肽，其中所述抗体域和所述接头在N端至C端方向具有以下顺序之一：a)VH-CH1-接头-VL-CL，b)VL-CL-接头-VH-CH1，c)VH-CL-接头-VL-CH1或d)VL-CH1-接头-VH-CL。特别地，所述接头是具有至少30个氨基酸，优选32至50个氨基酸之间的多肽。所述单链Fab片段经由CL域和CH1域之间的天然二硫键而被稳定化。另外，通过***半胱氨酸残基(例如根据Kabat编号在可变重链中的位置44和可变轻链中的位置100)产生链间 二硫键，这些单链Fab分子可以进一步被稳定化。
在另一个实施方案中，抗体片段是单链可变片段(scFv)。“单链可变片段(scFv)”是通过接头连接的抗体的重链可变区(VH)和轻链可变区(VL)的融合蛋白。特别地，接头是10至25个氨基酸的短多肽且通常富含有关柔性的甘氨酸，以及有关溶解性的丝氨酸或苏氨酸，并且可将VH的N端与VL的C端连接，或反之亦然。尽管去除了恒定区并引入了接头，但这种蛋白质保留了原始抗体的特异性。关于scFv片段的综述，见例如Pluckthün，于The Pharmacology of Monoclonal Antibodies，第113卷，Rosenburg和Moore编，(Springer-Verlag，New York)，第269-315页(1994)；还可见WO 93/16185；和美国专利No.5,571,894和5,587,458。
在另一个实施方案中，抗体片段是单域抗体。单域抗体是包含抗体的整个或部分重链可变域或整个或部分轻链可变域的抗体片段。在某些实施方案中，单域抗体是人单域抗体(Domantis，Inc.，Waltham，MA；见例如美国专利No.6,248,516 B1)。
可以通过多种技术，包括但不限于对完整抗体的蛋白水解消化及重组宿主细胞(例如大肠杆菌或噬菌体)的生成来生成抗体片段，如本文中所描述的。
3.嵌合的和人源化的抗体
在某些实施方案中，本文中提供的抗体是嵌合抗体。某些嵌合抗体记载于例如美国专利No.4,816,567；和Morrison et al.，Proc.Natl.Acad.Sci.USA，81：6851-6855(1984))。在一个例子中，嵌合抗体包含非人可变区(例如自小鼠，大鼠，仓鼠，家兔，或非人灵长类，诸如猴衍生的可变区)和人恒定区。在又一个例子中，嵌合抗体是“类转换的”抗体，其中类或亚类已经自亲本抗体的类或亚类改变。嵌合抗体包括其抗原结合片段。
在某些实施方案中，嵌合抗体是人源化抗体。通常，将非人抗体人源化以降低对人的免疫原性，同时保留亲本非人抗体的特异性和亲和力。一般地，人源化抗体包含一个或多个可变域，其中HVR，例如CDR(或其部分)自非人抗体衍生，而FR(或其部分)自人抗体序列衍生。任选地，人源化抗体还会至少包含人恒定区的一部分。在一些实施方案中，将人源化抗体中的一些FR残基用来自非人抗体(例如衍生HVR残基的抗体)的相应残基替代，例如以恢复或改善抗体特异性或亲和力。
人源化抗体及其生成方法综述于例如Almagro and Fransson，Front.Biosci.13：1619-1633(2008)，并且进一步记载于例如Riechmann et al.，Nature 332：323-329(1988)；Queen et al.，Proc.Nat’l Acad.Sci.USA 86：10029-10033(1989)；美国专利No.5，821，337，7，527，791，6，982，321和7，087，409；Kashmiri et al.，Methods 36：25-34(2005)(描述了特异性决定区(SDR)嫁接)；Padlan，Mol.Immunol.28：489-498(1991)(描述了“重修表面”)；Dall’Acqua et al.，Methods 36：43-60(2005)(描述了“FR改组”)；和Osbourn et al.，Methods36：61-68(2005)和Klimka et al.，Br.J.Cancer 83：252-260(2000)(描述了FR改组的“引导选择”方法)。
可以用于人源化的人框架区包括但不限于：使用“最佳拟合(best-fit)”方法选择的框架区(见例如Sims et al.，J.Immunol.151：2296(1993))；自轻或重链可变区的特定亚组的人抗体的共有序列衍生的框架区(见例如Carter et al.Proc.Natl.Acad.Sci.USA，89：4285(1992)；和Presta et al.，J.Immunol.，151：2623(1993))；人成熟的(体细胞突变的)框架区或人种系框架区(见例如Almagro and Fransson，Front.Biosci.13：1619-1633(2008))；和通过筛选FR文库衍生的框架区(见例如Baca et al.，J.Biol.Chem.272：10678-10684(1997)和Rosok et al.，J.Biol.Chem.271：22611-22618(1996))。
4.人抗体
在某些实施方案中，本文中提供的抗体是人抗体。可以使用本领域中已知的多种技术来生成人抗体。一般地，人抗体记载于van Dijk and van de Winkel，Curr.Opin.Pharmacol.5：368-74(2001)和Lonberg，Curr.Opin.Immunol.20：450-459(2008)。
可以通过对转基因动物施用免疫原来制备人抗体，所述转基因动物已经修饰为响应抗原性攻击而生成完整人抗体或具有人可变区的完整抗体。此类动物通常含有所有或部分人免疫球蛋白基因座，其替换内源免疫球蛋白基因座，或者其在染色体外存在或随机整合入动物的染色体中。在此类转基因小鼠中，一般已经将内源免疫球蛋白基因座灭活。关于自转基因动物获得人抗体的方法的综述，见Lonberg，Nat.Biotech.23：1117-1125(2005)。还可见例如美国专利No.6,075,181和6,150,584，其描述了XENOMOUSETM技术；美国专利No.5,770,429，其描述了技术；美国专利No.7,041,870，其描述了K-M技术，和美国专利申请公开文本No.US 2007/0061900，其描述了技术)。可以例如通过与不同人恒定区组合进一步修饰来自由此类动物生成的完整抗体的人可变区。
也可以通过基于杂交瘤的方法生成人抗体。已经描述了用于生成人单克隆抗体的人骨髓瘤和小鼠-人异源骨髓瘤细胞系(见例如Kozbor，J.Immunol.，133：3001(1984)；Brodeur et al.，Monoclonal Antibody Production Techniques and Applications，第51-63页(Marcel Dekker，Inc.，New York，1987)；和Boerner et al.，J.Immunol.，147：86(1991))。经由人B细胞杂交瘤技术生成的人抗体也记载于Li et al.，Proc.Natl.Acad.Sci.USA，103：3557-3562(2006)。其它方法包括那些例如记载于美国专利No.7，189，826(其描述了自杂交瘤细胞系生成单克隆人IgM抗体)和Ni，Xiandai Mianyixue，26(4)：265-268(2006)(其描述了人-人杂交瘤)的。人杂交瘤技术(Trioma技术)也记载于Vollmers and Brandlein，Histology and Histopathology，20(3)：927-937(2005)和Vollmers and Brandlein，Methods and Findings in Experimental and Clinical Pharmacology，27(3)：185-91(2005)。
也可以通过分离自人衍生的噬菌体展示文库选择的Fv克隆可变域序列生成人抗体。然后，可以将此类可变域序列与期望的人恒定域组合。下文描述了自抗体文库选择人抗体的技术。
5.文库衍生的抗体
可以通过对组合文库筛选具有期望的一种或多种活性的抗体来分离本发明的抗体。用于筛选组合文库的方法综述于例如Lerner et al.，Nature Reviews 16：498-508(2016)。例如，用于生成噬菌体展示文库并对此类文库筛选拥有期望结合特征的抗体的多种方法是本领域中已知的。此类方法综述于例如Frenzel et al.，mAbs 8：1177-1194(2016)；Bazan et al.，Human Vaccines and Immunotherapeutics 8：1817-1828(2012)和Zhao et al.，Critical Reviews in Biotechnology 36：276-289(2016)和Hoogenboom et al.，于Methods in Molecular Biology 178：1-37(O’Brien等编，Human Press，Totowa，NJ，2001)和Marks and Bradbury，于Methods in Molecular Biology 248：161-175(Lo编，Human Press，Totowa，NJ，2003)。
在某些噬菌体展示方法中，将VH和VL基因的全集分别通过聚合酶链式反应(PCR)克隆，并在噬菌体文库中随机重组，然后可以对所述噬菌体文库筛选抗原结合噬菌体，如记载于Winter et al.，AnnualReview of Immunology 12：433-455(1994)的。噬菌体通常以单链Fv(scFv)片段或以Fab片段展示抗体片段。来自经免疫的来源的文库提供针对免疫原的高亲和力抗体，而不需要构建杂交瘤。或者，可以(例如自人)克隆未免疫全集以在没有任何免疫接种的情况中提供针对一大批非自身和还有自身抗原的抗体的单一来源，如由Griffiths et al.，EMBO Journal 12：725-734(1993)描述的。最后，也可以通过自干细胞克隆未重排的V基因区段，并使用含有随机序列的PCR引物编码高度可变的CDR3区并在体外实现重排来合成生成未免疫文库，如由Hoogenboom and Winter，Journal of Molecular Biology 227：381-388(1992)所描述的。描述人抗体噬菌体文库的专利公开文本包括例如：美国专利No.5,750,373；7,985,840；7,785,903和8,679,490和美国专利公开文本No.2005/0079574，2007/0117126，2007/0237764和2007/0292936。
本领域知道的用于对组合文库筛选具有一种或多种期望活性的抗体的方法的别的例 子包括核糖体和mRNA展示，以及用于在细菌，哺乳动物细胞，昆虫细胞或酵母细胞上展示和选择抗体的方法。用于酵母表面展示的方法的综述见例如Scholler et al.，Methods in Molecular Biology 503：135-56(2012)和Cherf et al.，Methods in Molecular biology 1319：155-175(2015)以及Zhao et al.，Methods in Molecular Biology 889：73-84(2012)。用于核糖体展示的方法的记载见例如He et al.，Nucleic Acids Research 25：5132-5134(1997)和Hanes et al.，PNAS 94：4937-4942(1997)。
认为自人抗体文库分离的抗体或抗体片段是本文中的人抗体或人抗体片段。
6.多特异性抗体
在某些实施方案中，本文中提供的抗体是多特异性抗体，例如双特异性抗体。多特异性抗体是对至少两种不同位点(即不同抗原上的不同表位或相同抗原上的不同表位)具有结合特异性的单克隆抗体。在某些实施方案中，多特异性抗体具有三种或更多种结合特异性。在某些实施方案中，结合特异性之一针对RSV，而其它(两种或更多种)特异性针对任何其它抗原。在某些实施方案中，双特异性抗体可以结合RSV的两种(或更多种)不同抗原或表位。也可以使用多特异性(例如双特异性)抗体来将细胞毒性药剂或细胞定位于感染了RSV的细胞。多特异性抗体可以以全长抗体或抗体片段制备。
用于生成多特异性抗体的技术包括但不限于具有不同特异性的两对免疫球蛋白重链-轻链的重组共表达(见Milstein and Cuello，Nature 305：537(1983))，和“节-入-穴”工程化(见例如美国专利No.5,731,168和Atwell et al.，J.Mol.Biol.270：26(1997))。也可以通过用于生成抗体Fc-异二聚体分子的工程化静电操纵效应(见例如WO 2009/089004)；交联两种或更多种抗体或片段(见例如美国专利No.4,676,980，和Brennan et al.，Science，229：81(1985))；使用亮氨酸拉链来生成双特异性抗体(见例如Kostelny et al.，J.Immunol.，148(5)：1547-1553(1992)和WO 2011/034605)；使用共同轻链技术来规避轻链错配问题(见例如WO 98/50431)；使用用于生成双特异性抗体片段的“双抗体”技术(见例如Hollinger et al.，Proc.Natl.Acad.Sci.USA，90：6444-6448(1993))；和使用单链Fv(sFv)二聚体(见例如Gruber et al.，J.Immunol.，152：5368(1994))；和如例如Tutt et al.J.Immunol.147：60(1991)中所描述的，制备三特异性抗体来生成多特异性抗体。
本文中还包括具有三个或更多个抗原结合位点的工程化改造抗体，包括例如“章鱼抗体”或DVD-Ig(见例如WO 2001/77342和WO 2008/024715)。具有三个或更多个抗原结合位点的多特异性抗体的其它例子可以在WO 2010/115589，WO 2010/112193，WO 2010/136172，WO2010/145792，和WO 2013/026831中找到。双特异性抗体或其抗原结合片段还包括包含结合RSV和另一种不同抗原，或RSV的两种不同表位的抗原结合位点的“双重作用FAb”或“DAF”(见例如US 2008/0069820和WO 2015/095539)。
多特异性抗体还可以以不对称形式提供，其具有一个或多个具有相同抗原特异性的结合臂中的域交换，即通过交换VH/VL域(见例如WO 2009/080252和WO 2015/150447)，CH1/CL域(见例如WO 2009/080253)或整个Fab臂(见例如WO 2009/080251，WO 2016/016299，还见Schaefer et al.，PNAS，108(2011)1187-1191，和Klein et al.，MAbs 8(2016)1010-20)。在一个实施方案中，多特异性抗体包含交叉Fab片段。术语“交叉Fab片段”或“xFab片段”或“交换Fab片段”指如下的Fab片段，其中重和轻链的可变区或恒定区是交换的。交叉Fab片段包含由轻链可变区(VL)和重链恒定区(CH1)构成的多肽链，和由重链可变区(VH)和轻链恒定区(CL)构成的多肽链。还可以通过将带电荷的或不带电荷的氨基酸突变引入域界面以指导正确的Fab配对来改造不对称Fab臂。见例如WO 2016/172485。
多特异性抗体的各种别的分子型式是本领域知道的且包括在本文中(见例如Spiess et al.，Mol Immunol 67(2015)95-106)。
7.抗体变体
在某些实施方案中，涵盖本文中提供的抗体的氨基酸序列变体。例如，可以期望改善 抗体的结合亲和力和/或其它生物学特性。可以通过将合适的修饰引入编码抗体的核苷酸序列中，或者通过肽合成来制备抗体的氨基酸序列变体。此类修饰包括例如对抗体的氨基酸序列内的残基的删除，和/或***和/或替代。可以进行删除，***，和替代的任何组合以得到最终的构建体，只要最终的构建体拥有期望的特征，例如抗原结合。
a)替代，***，和删除变体
在某些实施方案中，提供了具有一处或多处氨基酸替代的抗体变体。替代诱变感兴趣的位点包括HVR和FR。保守替代在表A中在“优选的替代”的标题下显示。更实质的变化在表A中在“例示性替代”的标题下提供，并且如下文参照氨基酸侧链类别进一步描述的。可以将氨基酸替代引入感兴趣的抗体中，并且对产物筛选期望的活性，例如保留/改善的抗原结合，降低的免疫原性，或改善的ADCC或CDC。
表A
依照共同的侧链特性，氨基酸可以如下分组：
(1)疏水性的：正亮氨酸，Met，Ala，Val，Leu，Ile；
(2)中性，亲水性的：Cys，Ser，Thr，Asn，Gln；
(3)酸性的：Asp，Glu；
(4)碱性的：His，Lys，Arg；
(5)影响链取向的残基：Gly，Pro；
(6)芳香族的：Trp，Tyr，Phe。
非保守替代会需要用这些类别之一的成员替换另一个类别的。
一类替代变体牵涉替代亲本抗体(例如人源化或人抗体)的一个或多个高变区残基。一般地，为进一步研究选择的所得变体相对于亲本抗体会具有某些生物学特性的改变(例如改善)(例如升高的亲和力，降低的免疫原性)和/或会基本上保留亲本抗体的某些生物学特性。一种例示性的替代变体是亲和力成熟的抗体，其可以例如使用基于噬菌体展示的亲和力成熟技术诸如本文中所描述的那些技术来方便地生成。简言之，将一个或多个HVR 残基突变，并将变体抗体在噬菌体上展示，并对其筛选特定的生物学活性(例如结合亲和力)。
可以对HVR做出变化(例如替代)，例如以改善抗体亲和力。可以对HVR“热点”，即由在体细胞成熟过程期间以高频率经历突变的密码子编码的残基(见例如Chowdhury，Methods Mol.Biol.207：179-196(2008))，和/或接触抗原的残基做出此类变化，其中对所得的变体VH或VL测试结合亲和力。通过次级文库的构建和再选择进行的亲和力成熟已经记载于例如Hoogenboom et al.，于Methods in Molecular Biology 178：1-37(O’Brien等编，Human Press，Totowa，NJ，(2001))。在亲和力成熟的一些实施方案中，通过多种方法(例如易错PCR，链改组，或寡核苷酸指导的诱变)任一将多样性引入为成熟选择的可变基因。然后，创建次级文库。然后，筛选文库以鉴定具有期望的亲和力的任何抗体变体。另一种引入多样性的方法牵涉HVR指导的方法，其中将几个HVR残基(例如一次4-6个残基)随机化。可以例如使用丙氨酸扫描诱变或建模来特异性鉴定牵涉抗原结合的HVR残基。特别地，经常靶向CDR-H3和CDR-L3。
在某些实施方案中，可以在一个或多个HVR内发生替代，***，或删除，只要此类变化不实质性降低抗体结合抗原的能力。例如，可以对HVR做出保守变化(例如保守替代，如本文中提供的)，其不实质性降低结合亲和力。此类变化可以例如在HVR中的抗原接触残基外部。在上文提供的变体VH和VL序列的某些实施方案中，每个HVR是未改变的，或者含有不超过1，2或3处氨基酸替代。
一种可用于鉴定抗体中可以作为诱变靶位的残基或区域的方法称作“丙氨酸扫描诱变”，如由Cunningham and Wells(1989)Science，244：1081-1085所描述的。在此方法中，将一个残基或一组靶残基(例如带电荷的残基，诸如Arg，Asp，His，Lys，和Glu)鉴定，并用中性或带负电荷的氨基酸(例如丙氨酸或多丙氨酸)替换以测定抗体与抗原的相互作用是否受到影响。可以在对初始替代表明功能敏感性的氨基酸位置引入进一步的替代。或者/另外，抗原-抗体复合物的晶体结构来鉴定抗体与抗原间的接触点。作为替代的候选，可以靶向或消除此类接触残基和邻近残基。可以筛选变体以确定它们是否含有期望的特性。
氨基酸序列***包括长度范围为1个残基至含有100或更多个残基的多肽的氨基和/或羧基端融合，和单个或多个氨基酸残基的序列内***。末端***的例子包括具有N端甲硫氨酰基残基的抗体。抗体分子的其它***变体包括抗体的N或C端与酶(例如对于ADEPT)或延长抗体的血清半衰期的多肽的融合物。
b)糖基化变体
在某些实施方案中，改变本文中提供的抗体以提高或降低抗体糖基化的程度。可以通过改变氨基酸序列，使得创建或消除一个或多个糖基化位点来方便地实现抗体的糖基化位点的添加或删除。
在抗体包含Fc区的情况中，可以改变附着于它的寡糖。由哺乳动物细胞生成的天然抗体通常包含分支的，双触角的寡糖，其一般通过N连接附着于Fc区的CH2域的Asn297。见例如Wright et al.，TIBTECH 15：26-32(1997)。寡糖可以包括各种碳水化合物，例如甘露糖，N-乙酰葡糖胺(GlcNAc)，半乳糖，和唾液酸，以及附着于双触角寡糖结构“主干”中的GlcNAc的岩藻糖。在一些实施方案中，可以对本发明抗体中的寡糖进行修饰以创建具有某些改善的特性的抗体变体。
在一个实施方案中，提供了抗体变体，其具有附着(直接或间接)于Fc区的非岩藻糖基化寡糖，即缺乏岩藻糖的寡糖结构。此类非岩藻糖基化寡糖(也称作“无岩藻糖基化”寡糖)特别是缺乏附着于双触角寡糖结构的主干中的第一个GlcNAc的岩藻糖残基的N连接的寡糖。在一个实施方案中，提供了具有Fc区中与天然或亲本抗体相比升高比例的非岩藻糖基化寡糖的抗体变体。例如，非岩藻糖基化寡糖的比例可以是至少约20％，至少约40％，至少约60％，至少约80％，或甚至约100％(即不存在岩藻糖基化寡糖)。非岩藻糖基化寡糖的 百分比是相对于附着于Asn297的所有寡糖(例如复合的，杂合的和高甘露糖的结构)的总和，缺乏岩藻糖残基的寡糖的(平均)量，如通过MALDI-TOF质谱术测量的，例如记载于WO 2006/082515的。Asn297指位于Fc区中的约第297位(Fc区残基的EU编号方式)的天冬酰胺残基；然而，Asn297也可以由于抗体中的微小序列变异而位于第297位上游或下游约±3个氨基酸，即在第294位和第300位之间。此类具有Fc区中升高比例的非岩藻糖基化寡糖的抗体可以具有改善的FcRγIIIa受体结合和/或改善的效应器功能，特别是改善的ADCC功能。见例如US 2003/0157108；US 2004/0093621。
能够生成具有降低的岩藻糖基化的抗体的细胞系的例子包括蛋白质岩藻糖基化缺陷的Lec13CHO细胞(Ripka et al.，Arch.Biochem.Biophys.249：533-545(1986)；US 2003/0157108；和WO 2004/056312，尤其在实施例11)，和敲除细胞系，诸如α-1，6-岩藻糖基转移酶基因FUT8敲除CHO细胞(见例如Yamane-Ohnuki et al.，Biotech.Bioeng.87：614-622(2004)；Kanda，Y.et al.，Biotechnol.Bioeng.，94(4)：680-688(2006)；和WO 2003/085107)，或GDP-岩藻糖合成或转运蛋白活性降低或消除的细胞(见例如US2004259150，US2005031613，US2004132140，US2004110282)。
在又一个实施方案中，提供了具有两分型寡糖的抗体变体，例如其中附着于抗体Fc区的双触角寡糖是通过GlcNAc两分的。此类抗体变体可以具有如上所述降低的岩藻糖基化和/或改善的ADCC功能。此类抗体变体的例子记载于例如Umana et al.，Nat Biotechnol17，176-180(1999)；Ferrara et al.，Biotechn Bioeng 93，851-861(2006)；WO 99/54342；WO 2004/065540，WO 2003/011878。
还提供了在附着于Fc区的寡糖中具有至少一个半乳糖残基的抗体变体。此类抗体变体可以具有改善的CDC功能。此类抗体变体记载于例如WO 1997/30087；WO 1998/58964；和WO 1999/22764。
c)Fc区变体
在某些实施方案中，可以将一处或多处氨基酸修饰引入本文中提供的抗体的Fc区中，由此生成Fc区变体。Fc区变体可以包含在一个或多个氨基酸位置包含氨基酸修饰(例如替代)的人Fc区序列(例如人IgG1，IgG2，IgG3或IgG4Fc区)。
在某些实施方案中，本发明涵盖拥有一些但不是所有效应器功能的抗体变体，这使其成为如下应用的期望候选物，其中抗体的体内半衰期是重要的，而某些效应器功能(诸如补体和ADCC)是不必要的或有害的。可以进行体外和/或体内细胞毒性测定法以确认CDC和/或ADCC活性的降低/消减。例如，可以进行Fc受体(FcR)结合测定法以确保抗体缺乏FcγR结合(因此有可能缺乏ADCC活性)，但是保留FcRn结合能力。介导ADCC的主要细胞NK细胞仅表达FcγRIII，而单核细胞表达FcγRI，FcγRII和FcγRIII。在Ravetch and Kinet，Annu.Rev.Immunol.9：457-492(1991)的第464页上的表3中汇总了造血细胞上的FcR表达。评估感兴趣分子的ADCC活性的体外测定法的非限制性例子记载于美国专利No.5，500，362(见例如Hellstrom，I.et al.，Proc.Nat’l Acad.Sci.USA 83：7059-7063(1986))和Hellstrom，I.et al.，Proc.Nat’l Acad.Sci.USA 82：1499-1502(1985)；5，821，337(见Bruggemann，M.et al.，J.Exp.Med.166：1351-1361(1987))。或者，可以采用非放射性测定方法(见例如用于流式细胞术的ACTITM非放射性细胞毒性测定法(CellTechnology，Inc.Mountain View，CA；和CytoTox非放射性细胞毒性测定法(Promega，Madison，WI))。对于此类测定法有用的效应细胞包括外周血单个核细胞(PBMC)和天然杀伤(NK)细胞。或者/另外，可以在体内评估感兴趣分子的ADCC活性，例如在动物模型中，诸如披露于Clynes et al.，Proc.Nat’l Acad.Sci.USA 95：652-656(1998)的。也可以实施C1q结合测定法以确认抗体不能结合C1q，并且因此缺乏CDC活性。见例如WO 2006/029879和WO 2005/100402中的C1q和C3c结合ELISA。为了评估补体激活，可以实施CDC测定法(见例如Gazzano-Santoro et al.，J.Immunol.Methods 202：163(1996)；Cragg，M.S.et al.，Blood 101： 1045-1052(2003)；和Cragg，M.S.and M.J.Glennie，Blood 103：2738-2743(2004))。也可以使用本领域中已知的方法来实施FcRn结合和体内清除/半衰期测定(见例如Petkova，S.B.et al.，Int’l.Immunol.18(12)：1759-1769(2006)；WO 2013/120929A1)。
具有降低的效应器功能的抗体包括那些具有Fc区残基238，265，269，270，297，327和329中的一个或多个的替代的(美国专利No.6,737,056)。此类Fc突变体包括在氨基酸位置265，269，270，297和327中的两处或更多处具有替代的Fc突变体，包括残基265和297替代成丙氨酸的所谓的“DANA”Fc突变体(美国专利No.7,332,581)。
描述了具有改善的或降低的对FcR的结合的某些抗体变体(见例如美国专利No.6,737,056；WO 2004/056312，和Shields et al.，J.Biol.Chem.9(2)：6591-6604(2001))。
在某些实施方案中，抗体变体包含具有改善ADCC的一处或多处氨基酸替代，例如Fc区的位置298，333，和/或334(残基的EU编号方式)的替代的Fc区。
在某些实施方案中，抗体变体包含具有一处或多处提高FcRn结合的氨基酸替代的Fc区，例如Fc区的位置252，和/或254，和/或256(EU残基编号方式)处的替代。在某些实施方案中，抗体变体包含具有位置252，254，和256处的氨基酸替代的Fc区。在一个实施方案中，替代是自人IgG1Fc区衍生的Fc区中的M252Y，S254T和T256E。
在某些实施方案中，抗体变体包含具有降低FcγR结合的氨基酸替代的Fc区，例如Fc区的位置234和235(EU残基编号方式)处的替代。在一个实施方案中，替代是L234A和L235A(LALA)。在某些实施方案中，抗体变体进一步包含自人IgG1Fc区衍生的Fc区中的D265A和/或P329G。在一个实施方案中，替代是自人IgG1Fc区衍生的Fc区中的L234A，L235A和P329G(LALA-PG)(见例如WO 2012/130831A1)。在另一个实施方案中，替代是自人IgG1Fc区衍生的Fc区中的L234A，L235A和D265A(LALA-DA)。
在一些实施方案中，对Fc区做出改变，其导致改变的(即改善的或降低的)C1q结合和/或补体依赖性细胞毒性(CDC)，例如记载于美国专利No.6，194，551，WO 99/51642，和Idusogie et al.，J.Immunol.164：4178-4184(2000)的。
具有延长的半衰期和改善的对新生儿Fc受体(FcRn)的结合的抗体记载于US2005/0014934A1(Hinton等)，新生儿Fc受体(FcRn)负责将母体IgG转移至胎儿(Guyer et al.，J.Immunol.117：587(1976)和Kim et al.，J.Immunol.24：249(1994))。那些抗体包含其中具有改善Fc区对FcRn结合的一处或多处替代的Fc区。此类Fc变体包括那些在Fc区残基238，252，254，256，265，272，286，303，305，307，311，312，317，340，356，360，362，376，378，380，382，413，424或434中的一处或多处具有替代，例如Fc区残基434的替代的(见例如美国专利No.7,371,826；Dall′Acqua，W.F.，et al.J.Biol.Chem.281(2006)23514-23524)。
已经通过定点诱变鉴定了对小鼠Fc-小鼠FcRn相互作用至关紧要的Fc区残基(见例如Dall’Acqua，W.F.，et al.J.Immunol 169(2002)5171-5180)。残基I253，H310，H433，N434，和H435(依照Kabat的EU编号方式)牵涉相互作用(Medesan，C.et al.，Eur.J.Immunol.26(1996)2533；Firan，M.et al.，Int.Immunol.13(2001)993；Kim，J.K.et al.，Eur.J.Immunol.24(1994)542)。发现残基I253，H310，和H435对于人Fc与鼠FcRn的相互作用是至关紧要的(Kim，J.K.et al.，Eur.J.Immunol.29(1999)2819)。对人Fc-人FcRn复合物的研究显示残基I253，S254，H435，和Y436对于相互作用是至关紧要的(Firan，M.et al.，Int.Immunol.13(2001)993；Shields，R.L.et al.，J.Biol.Chem.276(2001)6591-6604)。已经报告和检查残基248至259和301至317和376至382和424至437的多种突变体(Yeung，Y.A.et al.，J.Immunol.182(2009)7667-7671)。
在某些实施方案中，抗体变体包含具有一处或多处降低FcRn结合的氨基酸替代的Fc区，例如Fc区的位置253，和/或310，和/或435(EU残基编号方式)处的替代。在某些实施方案中，抗体变体包含具有位置253，310和435处的氨基酸替代的Fc区。在一个实施方案中，替代是自人IgG1Fc区衍生的Fc区中的I253A，H310A和H435A。见例如Grevys，A.et al.，J. Immunol.194(2015)5497-5508。
在某些实施方案中，抗体变体包含具有一处或多处降低FcRn结合的氨基酸替代的Fc区，例如Fc区的位置310，和/或433，和/或436(EU残基编号方式)处的替代。在某些实施方案中，抗体变体包含具有位置310，433和436处的氨基酸替代的Fc区。在一个实施方案中，替代是自人IgG1Fc区衍生的Fc区中的H310A，H433A和Y436A(见例如WO 2014/177460A1)。
还可见Duncan and Winter，Nature 322：738-40(1988)；美国专利No.5,648,260；美国专利No.5,624,821；和WO 94/29351，它们关注Fc区变体的其它例子。
B.重组方法和组合物
可以使用重组方法和组合物来生成抗体，例如记载于US 4,816,567的。为了这些方法，提供了一种或多种编码抗体的分离的核酸。
在天然抗体或天然抗体片段的情况中需要两种核酸，一种用于轻链或其片段且一种用于重链或其片段。此类核酸编码包含抗体VL的氨基酸序列和/或包含VH的氨基酸序列(例如抗体的轻和/或重链)。这些核酸可以在相同的表达载体上或在不同的表达载体上。
在具有异二聚体重链的双特异性抗体的情况中，需要四种核酸，一种用于第一轻链，一种用于包含第一异单体Fc区多肽的第二轻链，一种用于第二轻链，而一种用于包含第二异单体Fc区多肽的第二重链。四种核酸可以包含在一种或多种核酸分子或表达载体中。此类核酸编码包含抗体的第一VL的氨基酸序列和/或包含包括第一异单体Fc区的第一VH的氨基酸序列和/或包含第二VL的氨基酸序列和/或包含包括第二异单体Fc区的第二VH的氨基酸序列(例如抗体的第一和/或第二轻和/或第一和/或第二重链)。这些核酸可以在相同的表达载体上或在不同的表达载体上，正常情况下，这些核酸位于两种或三种表达载体上，即一种载体可包含超过一种这些核酸。这些双特异性抗体的例子是CrossMab和T细胞双特异性药剂(见例如Schaefer，W.et al，PNAS，108(2011)11187-1191)。例如，异单体重链之一包含所谓的“节突变”(T366W和任选地S354C或Y349C之一)且另一包含所谓的“穴突变”(T366S，L368A和Y407V和任选地Y349C或S354C)(见例如Carter，P.et al.，Immunotechnol.2(1996)73)。
在一个实施方案中，提供了编码本文中报告的方法中使用的抗体的分离的核酸。
在又一个实施方案中，提供了包含此类核酸的一种或多种载体(例如表达载体)。
在又一个实施方案中，提供了包含此类核酸的宿主细胞。
在一个此类实施方案中，宿主细胞包含(例如已经用下述各项转化)：
-在由形成二硫键的两条相同的轻链和两条相同的重链其包含VH和VL的片段构成的
抗体的情况中：
(1)包含核酸的载体，所述核酸编码包含抗体VL的氨基酸序列和包含抗体VH的氨基酸序列，或
(2)第一载体和第二载体，所述第一载体包含编码包含抗体VL的氨基酸序列的核酸，所述第二载体包含编码包含抗体VH的氨基酸序列的核酸。
-在具有异二聚体重链的双特异性抗体的情况中：
(1)包含编码如下氨基酸序列的第一对核酸的第一载体，所述氨基酸序列之一包含抗体的第一VL且另一包含第一VH，和包含编码如下氨基酸序列的第二对核酸的第二载体，所述氨基酸序列之一包含抗体的第二VL且另一包含第二VH，或
(2)包含编码如下氨基酸序列的第一核酸的第一载体，所述氨基酸序列包含可变域之一(优选轻链可变域)，包含编码如下氨基酸序列的一对核酸的第二载体，所述氨基酸序列之一包含轻链可变域且另一包含第一重链可变域，和包含编码如下氨基酸序列的一对核酸的第三载体，所述氨基酸序列之一包含与第二载体对应的另一轻链可变域且另一包含第二重链可变域，或
(3)包含编码如下氨基酸序列的核酸的第一载体，所述氨基酸序列包含抗体的第一VL，包含编码如下氨基酸序列的核酸的第二载体，所述氨基酸序列包含抗体的第一VH，包含编码如下氨基酸序列的核酸的第三载体，所述氨基酸序列包含抗体的第二VL，和包含编码如下氨基酸序列的核酸的第四载体，所述氨基酸序列包含抗体的第二VH。
在一个实施方案中，宿主细胞是真核的，例如中国仓鼠卵巢(CHO)细胞或淋巴样细胞(例如Y0，NS0，Sp20细胞)。在一个实施方案中，提供了生成抗RSV抗体的方法，其中该方法包括在适合于表达抗体的条件下培养包含编码抗体的核酸的宿主细胞，如上文提供的，并且任选地，自宿主细胞(或宿主细胞培养液)回收抗体。
对于抗RSV抗体的重组生成，将编码抗体的核酸(例如上文所描述的)分离，并***一种或多种载体中，以在宿主细胞中进一步克隆和/或表达。此类核酸可以使用常规规程(例如通过使用能够特异性结合编码抗体重链和轻链的基因的寡核苷酸探针)容易地分离和测序，或者通过重组方法生成或通过化学合成来获得。
适合于克隆或表达抗体编码载体的宿主细胞包括本文中所描述的原核或真核细胞。例如，可以在细菌中生成抗体，特别是在不需要糖基化和Fc效应器功能时。对于抗体片段和多肽在细菌中的表达，见例如US 5,648,237，US 5,789,199和US 5,840,523(还可见Charlton，K.A.，于Methods in Molecular Biology，第248卷，Lo，B.K.C.编，Humana Press，Totowa，NJ(2003)，第245-254页，其描述了抗体片段在大肠杆菌(E.coli.)中的表达)。表达后，可以将抗体在可溶性级分中自细菌细胞团糊分离，并可以进一步纯化。
在原核生物外，真核微生物诸如丝状真菌或酵母是适合于抗体编码载体的克隆或表达宿主，包括其糖基化途径已经“人源化”，导致生成具有部分或完全人的糖基化样式的抗体的真菌和酵母菌株。见Gerngross，T.U.，Nat.Biotech.22(2004)1409-1414；Li et al.，Nat.Biotech.24(2006)210-215。
适合于表达糖基化抗体的宿主细胞也自多细胞生物体(无脊椎动物和脊椎动物)衍生。无脊椎动物细胞的例子包括植物和昆虫细胞。已经鉴定出许多杆状病毒株，其可以与昆虫细胞一起使用，特别是用于转染草地夜蛾(Spodoptera frugiperda)细胞。
也可以利用植物细胞培养物作为宿主。见例如US 5,959,177，US 6,040,498，US 6,420,548，US 7,125,978和US 6,417,429(其描述了用于在转基因植物中生成抗体的PLANTIBODIESTM技术)。
也可以使用脊椎动物细胞作为宿主。例如，适应于在悬浮液中生长的哺乳动物细胞系可以是有用的。有用的哺乳动物宿主细胞系的其它例子是经SV40转化的猴肾CV1系(COS-7)；人胚肾系(293或293细胞，如记载于例如Graham，F.L.et al.，J.Gen Virol.36(1977)59-74的)；幼年仓鼠肾细胞(BHK)；小鼠塞托利(sertoli)细胞(TM4细胞，如记载于例如如Mather，J.P.，Biol.Reprod.23(1980)243-252的)；猴肾细胞(CV1)；非洲绿猴肾细胞(VERO-76)；人***细胞(HELA)；犬肾细胞(MDCK)；牛鼠(buffalo rat)肝细胞(BRL 3A)；人肺细胞(W138)；人肝细胞(Hep G2)；小鼠***肿瘤(MMT 060562)；TRI细胞，如记载于例如Mather，J.P.et al.，Annals N.Y.Acad.Sci.383(1982)44-68的；MRC 5细胞；和FS4细胞。其它有用的哺乳动物宿主细胞系包括中国仓鼠卵巢(CHO)细胞，包括DHFR-CHO细胞(Urlaub，G.et al.，Proc.Natl.Acad.Sci.USA 77(1980)4216-4220)；和骨髓瘤细胞系诸如Y0，NS0和Sp2/0。关于适合于抗体生成的某些哺乳动物宿主细胞系的综述，见例如Yazaki，P.and Wu，A.M.，Methods in Molecular Biology，第248卷，Lo，B.K.C.编，Humana Press，Totowa，NJ(2004)，第255-268页。
C.测定法
可以通过本领域中已知的多种测定法对本文中提供的抗RSV抗体鉴定，筛选，或表征其物理/化学特性和/或生物学活性。
1.结合测定法和其它测定法
一方面，对本发明的抗体测试其抗原结合活性，例如通过已知的方法诸如ELISA，Western印迹等来进行。
另一方面，可使用竞争测定法来鉴定与参照抗RSV抗体竞争对RSV或其抗原的结合的抗体。在某些实施方案中，此类竞争性抗体结合与参照抗RSV抗体所结合表位相同的表位(例如线性或构象表位)。用于定位抗体所结合表位的详细例示性方法见Morris(1996)“Epitope Mapping Protocols”，Methods in Molecular Biology vol.66(Humana Press，Totowa，NJ)。
在一种例示性竞争测定法中，在包含第一经标记抗体(其结合RSV或其抗原)(例如参照抗RSV抗体)和第二未标记抗体(其要测试与第一抗体竞争对RSV或其抗原的结合的能力)的溶液中温育固定化RSV或其抗原。第二抗体可存在于杂交瘤上清液中。作为对照，在包含第一经标记抗体但不包含第二未标记抗体的溶液中温育固定化RSV或其抗原。在允许第一抗体结合RSV或其抗原的条件下温育后，除去过量的未结合抗体，并测量与固定化RSV或其抗原联合的标记物的量。如果测试样品中与固定化RSV或其抗原联合的标记物的量与对照样品相比实质性降低，那么这指示第二抗体与第一抗体竞争对RSV或其抗原的结合。参见Harlow and Lane(1988)Antibodies：A Laboratory Manual ch.14(Cold Spring Harbor Laboratory，Cold Spring Harbor，NY)。
2.活性测定法
一方面，提供了用于鉴定具有生物学活性的抗RSV抗体的测定法。生物学活性可以包括例如抗RSV抗体抑制RSV感染宿主细胞。还提供了在体内和/或在体外具有此类生物学活性的抗体。
D.用于诊断和检测的方法和组合物
在某些实施方案中，本文中提供的任何抗RSV抗体可用于检测生物学样品中RSV的存在。在用于本文时，术语“检测”涵盖定量或定性检测。在某些实施方案中，生物学样品包含细胞或组织，诸如肿瘤组织。
在一个实施方案中，提供了在诊断或检测方法中使用的抗RSV抗体。在又一方面，提供了检测生物学样品中RSV的存在的方法。在某些实施方案中，该方法包括在容许抗RSV抗体结合RSV或其抗原的条件下使生物学样品与抗RSV抗体接触，如本文中所描述的，并检测是否在抗RSV抗体与RSV或其抗原之间形成复合物。此类方法可以是体外或体内方法。在一个实施方案中，使用抗RSV抗体来选择适合用抗RSV抗体治疗的受试者，例如其中患者感染了RSV，或怀疑感染RSV，或有接触RSV的风险。
在某些实施方案中，提供了经标记的抗RSV抗体。标记物包括但不限于直接检测的标记物或模块(诸如荧光，发色，电子致密，化学发光，和放射性标记物)，和例如经由酶反应或分子相互作用间接检测的模块，诸如酶或配体。例示性的标记物包括但不限于放射性同位素32P，14C，125I，3H，和131I，荧光团诸如稀土螯合物或荧光素及其衍生物，罗丹明(rhodamine)及其衍生物，丹酰，伞形酮，萤光素酶，例如萤火虫萤光素酶和细菌萤光素酶(美国专利No.4,737,456)，萤光素，2，3-二氢酞嗪二酮，辣根过氧化物酶(HRP)，碱性磷酸酶，β-半乳糖苷酶，葡糖淀粉酶，溶菌酶，糖类氧化酶，例如葡萄糖氧化酶，半乳糖氧化酶，和葡萄糖-6-磷酸脱氢酶，杂环氧化酶诸如尿酸酶和黄嘌呤氧化酶(其与采用过氧化氢氧化染料前体的酶诸如HRP偶联)，乳过氧化物酶，或微过氧化物酶，生物素/亲合素，自旋标记物，噬菌体标记物，稳定的自由基，等等。
E.药学配制剂
通过混合具有期望纯度的此类抗体与一种或多种任选的药学可接受载剂(Remington’s Pharmaceutical Sciences第16版，Osol，A.编(1980))以冻干配制剂或水性溶液形式制备如本文中所描述的抗RSV抗体的药学配制剂。一般地，药学可接受载剂在所采用的剂量和浓度对接受者是无毒的，而且包括但不限于缓冲剂，诸如磷酸盐，柠檬酸盐，和 其它有机酸；抗氧化剂，包括抗坏血酸和甲硫氨酸；防腐剂(诸如氯化十八烷基二甲基苄基铵；氯化己烷双胺；苯扎氯铵，苯索氯铵；酚，丁醇或苯甲醇；对羟基苯甲酸烃基酯，诸如对羟基苯甲酸甲酯或丙酯；邻苯二酚；间苯二酚；环己醇；3-戊醇；和间甲酚)；低分子量(少于约10个残基)多肽；蛋白质，诸如血清白蛋白，明胶或免疫球蛋白；亲水性聚合物，诸如聚乙烯吡咯烷酮；氨基酸，诸如甘氨酸，谷氨酰胺，天冬酰胺，组氨酸，精氨酸或赖氨酸；单糖，二糖和其它碳水化合物，包括葡萄糖，甘露糖或糊精；螯合剂，诸如EDTA；糖类，诸如蔗糖，甘露醇，海藻糖或山梨醇；成盐相反离子，诸如钠；金属复合物(例如Zn-蛋白质复合物)；和/或非离子表面活性剂，诸如聚乙二醇(PEG)。本文中的例示性的药学可接受载剂进一步包含间质药物分散剂诸如可溶性中性活性透明质酸酶糖蛋白(sHASEGP)，例如人可溶性PH-20透明质酸酶糖蛋白，诸如rHuPH20(Baxter International，Inc.)。某些例示性的sHASEGP和使用方法，包括rHuPH20记载于美国专利公开文本No.2005/0260186和2006/0104968。在一方面，将sHASEGP与一种或多种别的糖胺聚糖酶诸如软骨素酶组合。
例示性的冻干抗体配制剂记载于美国专利No.6,267,958。水性抗体配制剂包括那些记载于美国专利No.6,171,586和WO2006/044908的，后一种配制剂包含组氨酸-乙酸盐缓冲剂。
本文中的配制剂还可含有超过一种所治疗具体适应症所必需的活性组分，优选那些活性互补且彼此没有不利影响的组分。此类活性组分适于以有效用于所需目的的量而组合存在。
活性组分可包载于例如通过凝聚技术或通过界面聚合制备的微胶囊中(例如分别是羟甲基纤维素或明胶微胶囊和聚(甲基丙烯酸甲酯)微胶囊)，在胶状药物投递***中(例如脂质体，清蛋白微球体，微乳剂，纳米颗粒和纳米胶囊)，或在粗滴乳状液中。此类技术披露于Remington′s Pharmaceutical Sciences，第16版，Osol，A.编(1980)。
可以制备持续释放制剂。持续释放制剂的合适的例子包括含有抗体的固体疏水性聚合物的半透性基质，该基质为成形商品形式，例如膜，或微胶囊。
用于体内施用的配制剂一般是无菌的。无菌性可容易地实现，例如通过穿过无菌滤膜过滤。
F.预防、治疗性方法和组合物
可以在预防或治疗性方法中使用本文中提供的任何抗RSV抗体。
在一个方面，提供了作为药物使用的抗RSV抗体。在又一些方面，提供了在预防或治疗RSV感染中使用的抗RSV抗体。在某些实施方案中，提供了在预防或治疗方法中使用的抗RSV抗体。在某些实施方案中，本发明提供了在预防具有RSV感染风险的个体的方法中使用的抗RSV抗体，所述预防包括对个体施用有效量的抗RSV抗体。在某些实施方案中，本发明提供了在治疗具有RSV感染的个体的方法中使用的抗RSV抗体，所述治疗包括对个体施用有效量的抗RSV抗体。在一个实施方案中，该抗体用于治疗RSV感染或延迟其进展。
依照任何上述实施方案的“个体”优选是人。在又一方面，本发明提供了抗RSV抗体在制造或制备药物中的用途。在一个实施方案中，所述药物用于治疗RSV感染。在又一个实施方案中，所述药物用于治疗RSV感染的方法，包括对具有RSV感染的个体施用有效量的所述药物。依照任何上述实施方案的“个体”可以是人。
如本文中使用的，术语“RSV感染”可以是例如下呼吸道感染。
在又一方面，本发明提供了治疗RSV感染的方法。在一个实施方案中，所述方法包括对具有癌症的个体施用有效量的抗RSV。依照任何上述实施方案的“个体”可以是人。
在又一方面，本发明提供了药学配制剂，其包含本文中提供的任何抗RSV抗体，例如在任何上述治疗性方法中使用。在一个实施方案中，药学配制剂包含本文中提供的任何抗 RSV抗体和药学可接受载剂。
在又一方面，本发明提供了药学配制剂，其包含本文中提供的任何抗RSV抗体，例如在任何上述治疗性方法中使用。在一个实施方案中，药学配制剂包含本文中提供的任何抗RSV抗体和药学可接受载剂。在另一个实施方案中，药学配制剂包含本文中提供的任何抗RSV抗体和至少一种别的治疗剂。在一个实施方案中，该至少一种别的治疗剂例如是另一种抗RSV抗体，其与本文中的抗RSV抗体结合RSV的不同表位。
可以单独或与疗法中的其它药剂组合使用本发明的抗体。例如，可以与至少一种别的治疗剂共施用本发明的抗体。
上文记录的此类联合疗法涵盖联合施用(其中两种或更多种治疗剂包含在相同或不同配制剂中)，和分开施用，在该情况中，可以在施用一种或多种别的治疗剂之前，同时，和/或之后发生本发明的抗体的施用。在一个实施方案中，抗RSV抗体的施用和别的治疗剂的施用彼此在约一个月内，或在约一，二或三周内，或在约一，二，三，四，五，或六天内发生。
可以通过任何合适的手段，包括胃肠外，肺内，和鼻内，及若期望用于局部治疗的话，损伤内施用来施用本发明的抗体(和任何别的治疗剂)。胃肠外输注包括肌肉内，静脉内，动脉内，腹膜内，或皮下施用。部分根据施用是短暂的还是长期的，剂量给药可以通过任何合适的路径，例如通过注射，诸如静脉内或皮下注射进行。本文中涵盖各种剂量给药日程表，包括但不限于单次施用或在多个时间点里的多次施用，推注施用，和脉冲输注。
本发明的抗体应当以符合良好的医学实践的方式配制，确定剂量和给药。关于这一点考虑的因素包括在治疗的特定病症，在治疗的特定哺乳动物，患者个体的临床状态，病因，药物递送部位，给药方法，服药日程以及其它为开业医生所知的因素。抗体无需但可任选地与一种或多种目前用于预防或治疗所述病症的药剂一起配制。上述其它药剂的有效量取决于配方中所存在的抗体的量，病症或治疗的类型，以及其它上述讨论的因素。这些药剂通常以与本文所述相同的剂量和给药途径使用，或以约1-99％的本文所描述的剂量使用，或以任何剂量并通过任何途径使用，所述剂量和途径是凭经验/临床确定合适的。
为了预防或治疗疾病，本发明的抗体(当单独或与一种或多种其它别的治疗剂联合使用时)的合适剂量会取决于所要治疗的疾病的类型，抗体的种类，疾病的严重性和病程，所给予抗体的预防或治疗目的，之前的治疗，患者的临床史和对抗体的应答，以及主治医师的斟酌决定。抗体适合于在一次或一系列的治疗中给予患者。取决于疾病的类型和严重性，约1μg/kg-15mg/kg(例如0.1mg/kg-10mg/kg)的抗体可作为首次候选剂量给予患者，无论是例如通过一次或多次分开的给药或通过连续输注。取决于上述提及的因素，一个典型的日剂量可在约1μg/kg-100mg/kg或更多的范围内。对于几天或更长时间的重复给药，取决于病情，治疗会通常持续直至出现疾病症状得到期望的抑制为止。抗体的一种例示性剂量会在约0.05mg/kg至约10mg/kg的范围中。如此，可以对患者施用约0.5mg/kg，2.0mg/kg，4.0mg/kg或10mg/kg(或它们的任意组合)的一剂或多剂。上述剂量可间歇给予，如每周或每三周给予一次(如使得患者得到约2剂-约20剂，或例如约6剂的抗体)。可给予初始较高的加载剂量，接着给予一个或多个较低的剂量。一种例示性剂量给药摄生法包括施用。然而，其它剂量摄生法可能是有用的。通过常规技术和测定方法易于监测该治疗的进展。
应当理解，可以替换抗RSV抗体或在抗RSV抗体外使用本发明的免疫缀合物实施任何上述配制剂或治疗性方法。
G.制品
在本发明的另一方面，提供了一种制品，其含有可用于治疗，预防和/或诊断上文所描述的病症的材料。制品包含容器和容器上或与容器联合的标签或包装插页。合适的容器包括例如瓶，管形瓶，注射器，IV溶液袋，等等。容器可以由多种材料诸如玻璃或塑料 形成。容器容纳单独或与另一种组合物组合有效治疗，预防和/或诊断状况的组合物，并且可以具有无菌存取口(例如，容器可以是具有由皮下注射针可穿过的塞子的管形瓶或静脉内溶液袋)。组合物中的至少一种活性剂是本发明的抗体。标签或包装插页指示使用组合物来治疗选择的状况。此外，制品可以包含：(a)其中装有组合物的第一容器，其中组合物包含本发明的抗体；和(b)其中装有组合物的第二容器，其中组合物包含别的治疗剂。在本发明的此实施方案中的制品可以进一步包含包装插页，其指示可以使用组合物来治疗特定的状况。或者/另外，制品可以进一步包含第二(或第三)容器，其包含药学可接受缓冲液，诸如抑菌性注射用水(BWFI)，磷酸盐缓冲盐水，Ringer氏溶液和右旋糖溶液。它可以进一步包含从商业和用户观点看期望的其它材料，包括其它缓冲液，稀释剂，滤器，针，和注射器。
氨基酸序列和核酸序列的描述






本发明提供一组抗体，对RSV A2 pre-F蛋白的亲和力在0.001nM到3.25nM之间，对RSV A2毒株的中和活性IC50在0.73ng/mL到80.04ng/mL之间，对RSV B9320毒株的中和活性IC50在1.11ng/mL到153.90ng/mL之间，对RSV B18537毒株的中和活性IC50在0.25 ng/mL到67.03ng/mL之间。
实施例1：抗RSV抗体的制备
从健康成人志愿者采集外周血，通过密度梯度离心法获得上层的血浆和中间的PBMC。用荧光标记的pre-F蛋白通过流式分选从PBMC中分离出与pre-F蛋白特异性结合的记忆B细胞，并利用巢式PCR获得可转染的具有表达活性的PCR片段，转染CHO细胞进行表达，得到含有分泌抗体的细胞上清液，通过ELISA进行结合活性筛选，获得了数百株pre-F结合阳性克隆。多株重组抗体经检测具有针对RSV A2毒株的中和活性。综合各重组抗体与RSV A2、RSV 9320及RSV 18537的中和活性，以及与RSV A2 pre-F蛋白的亲和力结果，最终选择了24株抗体，即F6-27、F6-37、F6-38、F6-47、F6-49、F6-56、F6-61、F6-63、F6-65、F6-70、F6-88、F6-115、F6-124、F6-132、F6-133、F6-141、F6-153、F6-172、F6-207、F6-208、F6-210、F6-213、F6-215和F6-227。
抗体的CDR的氨基酸序列显示于表1。
表1：抗RSV抗体的CDR的氨基酸序列

抗体的VH、VL和CL的氨基酸序列显示于表2。
表2：抗RSV抗体的VH、VL和CL的氨基酸序列



将抗体的轻、重链可变区的编码序列克隆到携带人IgG1恒定区编码序列的真核表达载体中，瞬时转染CHO细胞，进行分泌性表达，通过蛋白A亲和纯化获得了纯度＞90％的抗体蛋白，即F6-27、F6-37、F6-38、F6-47、F6-49、F6-56、F6-61、F6-63、F6-65、F6-70、F6-88、F6-115、F6-124、F6-132、F6-133、F6-141、F6-153、F6-172、F6-207、F6-208、F6-210、F6-213、F6-215和F6-227。
人IgG1恒定区的氨基酸序列：
RSV A2 pre-F氨基酸序列：
实施例2：抗RSV抗体的表征-通过ELISA表征抗原结合活性
将用pH 9.6的碳酸盐缓冲液释至2μg/mL的RSV A2 pre-F蛋白(Vazyme自制)以100μL/孔加入96孔酶标板(NEST，504201)，4℃包被过夜。去除溶液，用PBST清洗2次，并用封闭液(PBS+5％BSA)37℃封闭2小时。去除溶液，将用稀释液(PBS+5％BSA)3倍连续稀释的抗体(起始浓度5μg/mL，共10个梯度)以100μL/孔加入微孔板，37℃温育1小时。去除溶液，用PBST清洗3次，每孔加入100μL 1∶10000稀释的小鼠抗人IgG Fc-HRP(Vazyme自制)，37℃温育1小时。去除溶液，用PBST清洗3次，每孔加入100μL 显色底物TMB，37℃避光温育10分钟。去除溶液，用PBST清洗3次，每孔加入50μL 2M硫酸。在多功能酶标仪(Tecan，Spark)上测量450nm的OD值。进行四参数拟合，计算抗体的抗原结合活性的EC50值(ng/mL)，结果如表3.1、表3.2(表3.2与表3.1为不同次的实验结果，且表3.2实验的操作只有“将用稀释液(PBS+5％BSA)2倍连续稀释的抗体(起始浓度1μg/mL，共14个梯度)”处不同)所示。用GraphPad Prism 8.0对抗体浓度和OD值进行作图，结果如图1-1、图1-2所示。
表3.1：抗RSV抗体的RSV A2 pre-F结合活性的EC50值(ng/mL)

表3.2：抗RSV抗体的RSV A2 pre-F结合活性的EC50值(ng/mL)
实施例3：抗RSV抗体的表征-通过BLI表征亲和力
使用Octet蛋白质分析***(SARTORIUS，Octet R8)通过生物层干涉计量(Bio-Layer Interferometry，BLI)获得抗体的亲和力拟合曲线。传感器使用HIS1K(SARTORIUS，18-5120)，捕获剂为47.6nM RSV A2 pre-F蛋白，固定时间为120秒，抗体浓度为500nM、167nM、56nM、19nM、6nM、2nM和0.69nM，结合时间为60秒，解离时间为120秒，再生溶液为10mM甘氨酸-盐酸pH 1.5，再生时间为180秒。使用软件Octet Analysis Studio12.2计算抗体的抗原结合亲和力的KD值(M)，结果如表4.1、表4.2所示。使用软件Octet BLI Discovery 12.2进行记录，结果如图2-1、图2-2所示。
表4.1：抗RSV抗体的RSV A2 pre-F结合亲和力的KD值(M)
表4.2：抗RSV抗体的RSV A2 pre-F结合亲和力的KD值(M)
实施例4：抗RSV抗体的表征-通过体外微量中和测定法表征中和活性
将用PBS+5％HIFBS 3倍连续稀释的抗体(起始浓度0.5μg/mL，共7个梯度)以60μL/孔加入装有病毒(RSV A2，ATCC VR-1540；RSV B9320，ATCC VR-955；RSV B18537， ATCC VR-1580)(60μL/孔，500pfu)的96孔板(NEST，701001)，于细胞培养箱(37℃，5％CO2)中温育1小时。将50μL/孔上述混合液涂布到Hep2细胞汇合率达到90％的96孔板(NEST，701001)上(前一天以3×105个细胞/mL涂布)，于细胞培养箱(37℃，5％CO2)中温育2小时。去除上清液，每孔加入100μL补充有2％FBS和1％青霉素-链霉素(Solaibio，P1400)的DMEM培养基，继续温育21-22小时。去除上清液，每孔加入100μL 4％多聚甲醛，固定细胞10分钟。去除多聚甲醛，每孔加入250μL PBS清洗细胞1次，每孔加入100μL PBS+4％BSA，于细胞培养箱(37℃，5％CO2)中封闭30分钟。去除封闭液，每孔加入50μL稀释至5μg/mL的3D3荧光抗体(Vazyme自制)，于细胞培养箱(37℃，5％CO2)中温育1小时。去除抗体，用PBST清洗3次，甩干。使用荧光(酶联)免疫斑点分析仪(CTL，S6 Ultra M2)读取每个孔的斑点数。以单加细胞孔(细胞孔)作为阴性孔，以单加病毒孔(病毒孔)作为阳性孔。
用GraphPad Prism 8.0对抗体浓度和中和率进行作图，结果如图3-1、图3-2所示。进行四参数拟合，计算抗体的病毒中和活性的IC50值(ng/mL)，结果如表5.1、表5.2所示。
表5.1：抗RSV抗体的病毒中和活性的IC50值(ng/mL)
表5.2：抗RSV抗体的病毒中和活性的IC50值(ng/mL)

实施例5：抗RSV抗体的表征-通过竞争结合表征表位
将RSV A2 pre-F蛋白用缓冲液(PBS+0.02％Tween 20+0.1％BSA)稀释至10μg/mL，将抗体用上述缓冲液稀释至200nM，均以200μL/孔添加。如图4所示，在Octet蛋白质分析***(SARTORIUS，Octet R8)上运行上述缓冲液120秒以达到基线水平，运行抗原至信号达到0.3nm，运行上述缓冲液60秒以达到基线水平，运行第一抗体180秒，运行第二抗体180秒(第二抗体中加入同浓度的第一抗体以防止在第一抗体是快解离抗体的情况中在第二抗体结合时因第一抗体解离产生的假阳性结果)，重复3次交替运行再生液(10mM甘氨酸-盐酸，pH 1.5)和缓冲液共20秒。重复上述循环。
数据分析：
将第一抗体为Ab1、第二抗体为Ab2+Ab1时的第二信号设为H1’2；
将第一抗体为Ab1、第二抗体为Ab1时的第二信号设为H1’1；
则
第一抗体为Ab1、第二抗体为Ab2的第二信号为H1，＝H1’2-H1’1；
将第一抗体为0、第二抗体为Ab2时的第二信号设为H2；
则
第一抗体对第二抗体的抑制率为：1-(H1/H2)×100％
(调换两个抗体来计算第二抗体对第一抗体的抑制率)。
实验有效性判断：
自反应信号＜20％；否则，数据无效。
判定标准：
＞70％：完全竞争，一个方向达到这个标准即可；
30％-70％：部分竞争；
＜30％：完全不竞争，一个方向达到这个标准即可。
当待测抗体与已知表位的参照抗体完全竞争时，认为待测抗体与参照抗体结合相同表位。
如上所述计算抑制率，结果如表6.1、表6.2所示。已知参照抗体MEDI8897结合RSV 2A pre-F蛋白的表位，Motavizumab结合RSV 2A F蛋白的II表位，MPE8结合RSV 2A F蛋白的III表位，MK-1654结合RSV 2A F蛋白的IV表位。结果显示，F6-27、F6-37、F6-38、F6-47、F6-49、F6-56、F6-61、F6-63、F6-65、F6-70、F6-88、F6-115、F6-132、F6-141、F6-172、F6-207、F6-208、F6-210、F6-213、F6-215和F6-227与MEDI8897竞争，即这些抗体也识别F蛋白的表位；F6-124、F6-125和F6-153与MK-1654竞争，即这些抗体也识别pre-F蛋白的IV表位；F6-133同时与Motavizumab和MPE8竞争，即该抗体也识别F蛋白的II和III表位。
表6.1：抗RSV抗体的结合竞争


表6.2：抗RSV抗体的结合竞争
抗体可变区编码序列






Claims (25)

  1. 一种特异性结合RSV的抗体或其抗原结合片段，其包含：
    (1)如SEQ ID NO：1所示的CDR-H1，如SEQ ID NO：2所示的CDR-H2，如SEQ ID NO：3所示的CDR-H3，如SEQ ID NO：4所示的CDR-L1，如SEQ ID NO：5所示的CDR-L2，和如SEQ ID NO：6所示的CDR-L3；
    (2)如SEQ ID NO：9所示的CDR-H1，如SEQ ID NO：10所示的CDR-H2，如SEQ ID NO：11所示的CDR-H3，如SEQ ID NO：12所示的CDR-L1，如SEQ ID NO：13所示的CDR-L2，和如SEQ ID NO：14所示的CDR-L3；
    (3)如SEQ ID NO：17所示的CDR-H1，如SEQ ID NO：18所示的CDR-H2，如SEQ ID NO：19所示的CDR-H3，如SEQ ID NO：20所示的CDR-L1，如SEQ ID NO：21所示的CDR-L2，和如SEQ ID NO：22所示的CDR-L3；
    (4)如SEQ ID NO：25所示的CDR-H1，如SEQ ID NO：26所示的CDR-H2，如SEQ ID NO：27所示的CDR-H3，如SEQ ID NO：28所示的CDR-L1，如SEQ ID NO：29所示的CDR-L2，和如SEQ ID NO：30所示的CDR-L3；
    (5)如SEQ ID NO：33所示的CDR-H1，如SEQ ID NO：34所示的CDR-H2，如SEQ ID NO：35所示的CDR-H3，如SEQ ID NO：36所示的CDR-L1，如SEQ ID NO：37所示的CDR-L2，和如SEQ ID NO：38所示的CDR-L3；
    (6)如SEQ ID NO：41所示的CDR-H1，如SEQ ID NO：42所示的CDR-H2，如SEQ ID NO：43所示的CDR-H3，如SEQ ID NO：44所示的CDR-L1，如SEQ ID NO：45所示的CDR-L2，和如SEQ ID NO：46所示的CDR-L3；
    (7)如SEQ ID NO：49所示的CDR-H1，如SEQ ID NO：50所示的CDR-H2，如SEQ ID NO：51所示的CDR-H3，如SEQ ID NO：52所示的CDR-L1，如SEQ ID NO：53所示的CDR-L2，和如SEQ ID NO：54所示的CDR-L3；
    (8)如SEQ ID NO：57所示的CDR-H1，如SEQ ID NO：58所示的CDR-H2，如SEQ ID NO：59所示的CDR-H3，如SEQ ID NO：60所示的CDR-L1，如SEQ ID NO：61所示的CDR-L2，和如SEQ ID NO：62所示的CDR-L3；
    (9)如SEQ ID NO：65所示的CDR-H1，如SEQ ID NO：66所示的CDR-H2，如SEQ ID NO：67所示的CDR-H3，如SEQ ID NO：68所示的CDR-L1，如SEQ ID NO：69所示的CDR-L2，和如SEQ ID NO：70所示的CDR-L3；
    (10)如SEQ ID NO：73所示的CDR-H1，如SEQ ID NO：74所示的CDR-H2，如SEQ ID NO：75所示的CDR-H3，如SEQ ID NO：76所示的CDR-L1，如SEQ ID NO：77所示的CDR-L2，和如SEQ ID NO：78所示的CDR-L3；
    (11)如SEQ ID NO：81所示的CDR-H1，如SEQ ID NO：82所示的CDR-H2，如SEQ ID NO：83所示的CDR-H3，如SEQ ID NO：84所示的CDR-L1，如SEQ ID NO：85所示的CDR-L2，和如SEQ ID NO：86所示的CDR-L3；
    (12)如SEQ ID NO：89所示的CDR-H1，如SEQ ID NO：90所示的CDR-H2，如SEQ ID NO：91所示的CDR-H3，如SEQ ID NO：92所示的CDR-L1，如SEQ ID NO：93所示的CDR-L2，和如SEQ ID NO：94所示的CDR-L3；
    (13)如SEQ ID NO：97所示的CDR-H1，如SEQ ID NO：98所示的CDR-H2，如SEQ ID NO：99所示的CDR-H3，如SEQ ID NO：100所示的CDR-L1，如SEQ ID NO：101所示的CDR-L2，和如SEQ ID NO：102所示的CDR-L3；
    (14)如SEQ ID NO：105所示的CDR-H1，如SEQ ID NO：106所示的CDR-H2，如SEQ ID NO：107所示的CDR-H3，如SEQ ID NO：108所示的CDR-L1，如SEQ ID NO：109所示的CDR-L2，和如SEQ ID NO：110所示的CDR-L3；
    (15)如SEQ ID NO：113所示的CDR-H1，如SEQ ID NO：114所示的CDR-H2，如SEQ ID  NO：115所示的CDR-H3，如SEQ ID NO：116所示的CDR-L1，如SEQ ID NO：117所示的CDR-L2，和如SEQ ID NO：118所示的CDR-L3；
    (16)如SEQ ID NO：121所示的CDR-H1，如SEQ ID NO：122所示的CDR-H2，如SEQ ID NO：123所示的CDR-H3，如SEQ ID NO：124所示的CDR-L1，如SEQ ID NO：125所示的CDR-L2，和如SEQ ID NO：126所示的CDR-L3；
    (17)如SEQ ID NO：129所示的CDR-H1，如SEQ ID NO：130所示的CDR-H2，如SEQ ID NO：131所示的CDR-H3，如SEQ ID NO：132所示的CDR-L1，如SEQ ID NO：133所示的CDR-L2，和如SEQ ID NO：134所示的CDR-L3；
    (18)如SEQ ID NO：137所示的CDR-H1，如SEQ ID NO：138所示的CDR-H2，如SEQ ID NO：139所示的CDR-H3，如SEQ ID NO：140所示的CDR-L1，如SEQ ID NO：141所示的CDR-L2，和如SEQ ID NO：142所示的CDR-L3；
    (19)如SEQ ID NO：145所示的CDR-H1，如SEQ ID NO：146所示的CDR-H2，如SEQ ID NO：147所示的CDR-H3，如SEQ ID NO：148所示的CDR-L1，如SEQ ID NO：149所示的CDR-L2，和如SEQ ID NO：150所示的CDR-L3；
    (20)如SEQ ID NO：153所示的CDR-H1，如SEQ ID NO：154所示的CDR-H2，如SEQ ID NO：155所示的CDR-H3，如SEQ ID NO：156所示的CDR-L1，如SEQ ID NO：157所示的CDR-L2，和如SEQ ID NO：158所示的CDR-L3；
    (21)如SEQ ID NO：161所示的CDR-H1，如SEQ ID NO：162所示的CDR-H2，如SEQ ID NO：163所示的CDR-H3，如SEQ ID NO：164所示的CDR-L1，如SEQ ID NO：165所示的CDR-L2，和如SEQ ID NO：166所示的CDR-L3；
    (22)如SEQ ID NO：169所示的CDR-H1，如SEQ ID NO：170所示的CDR-H2，如SEQ ID NO：171所示的CDR-H3，如SEQ ID NO：172所示的CDR-L1，如SEQ ID NO：173所示的CDR-L2，和如SEQ ID NO：174所示的CDR-L3；
    (23)如SEQ ID NO：177所示的CDR-H1，如SEQ ID NO：178所示的CDR-H2，如SEQ ID NO：179所示的CDR-H3，如SEQ ID NO：180所示的CDR-L1，如SEQ ID NO：181所示的CDR-L2，和如SEQ ID NO：182所示的CDR-L3；或
    (24)如SEQ ID NO：185所示的CDR-H1，如SEQ ID NO：186所示的CDR-H2，如SEQ ID NO：187所示的CDR-H3，如SEQ ID NO：188所示的CDR-L1，如SEQ ID NO：189所示的CDR-L2，和如SEQ ID NO：190所示的CDR-L3。
  2. 根据权利要求1所述的抗体或其抗原结合片段，其包含：
    (1)如SEQ ID NO：7所示的VH和如SEQ ID NO：8所示的VL；
    (2)如SEQ ID NO：15所示的VH和如SEQ ID NO：16所示的VL；
    (3)如SEQ ID NO：23所示的VH和如SEQ ID NO：24所示的VL；
    (4)如SEQ ID NO：31所示的VH和如SEQ ID NO：32所示的VL；
    (5)如SEQ ID NO：39所示的VH和如SEQ ID NO：40所示的VL；
    (6)如SEQ ID NO：47所示的VH和如SEQ ID NO：48所示的VL；
    (7)如SEQ ID NO：55所示的VH和如SEQ ID NO：56所示的VL；
    (8)如SEQ ID NO：63所示的VH和如SEQ ID NO：64所示的VL；
    (9)如SEQ ID NO：71所示的VH和如SEQ ID NO：72所示的VL；
    (10)如SEQ ID NO：79所示的VH和如SEQ ID NO：80所示的VL；
    (11)如SEQ ID NO：87所示的VH和如SEQ ID NO：88所示的VL；
    (12)如SEQ ID NO：95所示的VH和如SEQ ID NO：96所示的VL；
    (13)如SEQ ID NO：103所示的VH和如SEQ ID NO：104所示的VL；
    (14)如SEQ ID NO：111所示的VH和如SEQ ID NO：112所示的VL；
    (15)如SEQ ID NO：119所示的VH和如SEQ ID NO：120所示的VL；
    (16)如SEQ ID NO：127所示的VH和如SEQ ID NO：128所示的VL；
    (17)如SEQ ID NO：135所示的VH和如SEQ ID NO：136所示的VL；
    (18)如SEQ ID NO：143所示的VH和如SEQ ID NO：144所示的VL；
    (19)如SEQ ID NO：151所示的VH和如SEQ ID NO：152所示的VL；
    (20)如SEQ ID NO：159所示的VH和如SEQ ID NO：160所示的VL；
    (21)如SEQ ID NO：167所示的VH和如SEQ ID NO：168所示的VL；
    (22)如SEQ ID NO：175所示的VH和如SEQ ID NO：176所示的VL；
    (23)如SEQ ID NO：183所示的VH和如SEQ ID NO：184所示的VL；或
    (24)如SEQ ID NO：191所示的VH和如SEQ ID NO：192所示的VL。
  3. 根据权利要求1所述的抗体或其抗原结合片段，其包含：
    (1)如SEQ ID NO：201所示的重链恒定区，和
    (2)如SEQ ID NO：193-200任一所示的轻链恒定区。
  4. 根据权利要求1所述的抗体或其抗原结合片段，其包含α重链、δ重链、ε重链、γ重链或μ重链。
  5. 根据权利要求1所述的抗体或其抗原结合片段，其属于IgG1、IgG2、IgG3或IgG4亚类。
  6. 根据权利要求1所述的抗体或其抗原结合片段，其包含λ轻链或κ轻链。
  7. 根据权利要求1所述的抗体或其抗原结合片段，其为全长抗体。
  8. 根据权利要求1所述的抗体或其抗原结合片段，其为选自Fv、scFv、Fab、Fab′、F(ab′)2和xFab的抗体片段。
  9. 根据权利要求1-8任一项所述的抗体或其抗原结合片段，其具有下述一项或多项特性：
    (1)能够特异性结合RSV A2 pre-F蛋白；
    (2)能够以小于62、61、60、59、50、40、36、35、32、31、30、29、25、24、23、22、21、20、19、18、17、16、15、14、13、12、11、10、9、8、7.5或7.2ng/mL的EC50值，或以比MEDI8897的EC50值小(例如1％至99％，例如至少5％、10％、15％、20％、25％、30％、35％、40％、45％、50％、55％、60％、65％、70％、75％、80％、85％、90％、95％或100％)的EC50值特异性结合RSV A2 pre-F蛋白；
    (3)能够以小于3.3、2.2、1.3、1.0、0.9、0.4、0.3、0.2、0.15、0.07、0.06或0.001nM的KD值，或以比MEDI8897的KD值小(例如1％至99％，例如至少5％、10％、15％、20％、25％、30％、35％、40％、45％、50％、55％、60％、65％、70％、75％、80％、85％、90％、95％或100％)的KD值特异性结合RSV A2 pre-F蛋白；
    (4)能够抑制RSV(例如A型和/或B型)感染宿主细胞；
    (5)能够以小于100、90、80、70、60、50、45、40、35、30、25、20、15、10、9、8、7、6、5、4、3、2或1.5ng/mL的IC50值，或以比MEDI8897的IC50值小(例如1％至99％，例如至少5％、10％、15％、20％、25％、30％、35％、40％、45％、50％、55％、60％、65％、70％、75％、80％、85％、90％、95％或100％)的IC50值抑制RSV A型株(例如A2)感染宿主细胞；
    (6)能够以小于160、150、140、130、120、110、100、90、80、70、60、50、40、30、20、15、10、9、8、7、6、5、4或3ng/mL的IC50值，或以比MEDI8897的IC50值小(例如1％至99％，例如至少5％、10％、15％、20％、25％、30％、35％、40％、45％、50％、55％、60％、65％、70％、75％、80％、85％、90％、95％或100％)的IC50值抑制RSV B型株(例如B9320)感染宿主细胞；
    (7)能够以小于80、70、60、50、45、40、35、30、20、15、10、9、8、7、6、5、4、3、2或1ng/mL的IC50值，或以比MEDI8897的IC50值小(例如1％至99％，例如至少5％、10％、15％、20％、25％、30％、35％、40％、45％、50％、55％、60％、65％、70％、75％、80％、85％、90％、95％或100％)的IC50值抑制RSV B型株(例如B18537) 感染宿主细胞；
    (8)能够竞争或抑制MEDI8897对RSV A2 pre-F蛋白的结合；
    (9)能够将MEDI8897对RSV A2 pre-F蛋白的结合抑制1％至100％，例如至少5％、10％、15％、20％、25％、30％、35％、40％、45％、50％、55％、60％、65％、70％、75％、80％、81％、82％、83％、84％、85％、86％、87％、88％、89％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％；
    (10)能够竞争或抑制MK-1654对RSV A2 pre-F蛋白的结合；
    (11)能够将MK-1654对RSV A2 pre-F蛋白的结合抑制1％至100％，例如至少5％、10％、15％、20％、25％、30％、35％、40％、45％、50％、55％、60％、65％、70％、75％、80％、81％、82％、83％、84％、85％、86％、87％、88％、89％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％；
    (12)能够竞争或抑制Motavizumab对RSV A2 pre-F蛋白的结合；
    (13)能够将Motavizumab对RSV A2 pre-F蛋白的结合抑制1％至100％，例如至少5％、10％、15％、20％、25％、30％、35％、40％、45％、50％、55％、60％、65％、70％、75％、80％、81％、82％、83％、84％、85％、86％、87％、88％、89％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％；
    (14)能够竞争或抑制MPE8对RSV A2 pre-F蛋白的结合；
    (15)能够将MPE8对RSV A2 pre-F蛋白的结合抑制1％至100％，例如至少5％、10％、15％、20％、25％、30％、35％、40％、45％、50％、55％、60％、65％、70％、75％、80％、81％、82％、83％、84％、85％、86％、87％、88％、89％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％；
    (16)能够结合RSV A2 pre-F蛋白的表位；
    (17)能够结合RSV A2 pre-F蛋白的IV表位；
    (18)能够结合RSV A2 pre-F蛋白的表位和IV表位；
    (19)能够结合RSV A2 pre-F蛋白的II表位；
    (20)能够结合RSV A2 pre-F蛋白的III表位；和/或
    (21)能够结合RSV A2 pre-F蛋白的II表位和III表位。
  10. 一种多核苷酸，其编码根据权利要求1-9任一项所述的抗体或其抗原结合片段。
  11. 根据权利要求10所述的多核苷酸，其包含：
    (1)SEQ ID NO：202和203；
    (2)SEQ ID NO：204和205；
    (3)SEQ ID NO：206和207；
    (4)SEQ ID NO：208和209；
    (5)SEQ ID NO：210和211；
    (6)SEQ ID NO：212和213；
    (7)SEQ ID NO：214和215；
    (8)SEQ ID NO：216和217；
    (9)SEQ ID NO：218和219；
    (10)SEQ ID NO：220和221；
    (11)SEQ ID NO：222和223；
    (12)SEQ ID NO：224和225；
    (13)SEQ ID NO：226和227；
    (14)SEQ ID NO：228和229；
    (15)SEQ ID NO：230和231；
    (16)SEQ ID NO：232和233；
    (17)SEQ ID NO：234和235；
    (18)SEQ ID NO：236和237；
    (19)SEQ ID NO：238和239；
    (20)SEQ ID NO：240和241；
    (21)SEQ ID NO：242和243；
    (22)SEQ ID NO：244和245；
    (23)SEQ ID NO：246和247；或
    (24)SEQ ID NO：248和249。
  12. 一种载体，其包含根据权利要求10或11所述的多核苷酸。
  13. 一种宿主细胞，其包含根据权利要求10或11所述的多核苷酸或根据权利要求12所述的载体。
  14. 根据权利要求13所述的宿主细胞，其为真核细胞。
  15. 根据权利要求14所述的宿主细胞，其为CHO细胞。
  16. 一种生成抗体或其抗原结合片段的方法，其包括：
    (a)在适合于表达该抗体或其抗原结合片段的条件下培养根据权利要求13-15任一项所述的宿主细胞，并
    (b)任选地，回收该抗体或其抗原结合片段。
  17. 一种组合物，其包含根据权利要求1-9任一项所述的抗体或其抗原结合片段。
  18. 根据权利要求1-9任一项所述的抗体或其抗原结合片段或根据权利要求17所述的组合物，其用作药物。
  19. 根据权利要求1-9任一项所述的抗体或其抗原结合片段或根据权利要求17所述的组合物，其用于治疗疾病。
  20. 根据权利要求19所述的抗体或其抗原结合片段或组合物，其中该疾病是下呼吸道感染。
  21. 根据权利要求1-9任一项所述的抗体或其抗原结合片段或根据权利要求17所述的组合物制造用于治疗疾病的药物的用途。
  22. 根据权利要求21所述的用途，其中该疾病是下呼吸道感染。
  23. 一种治疗个体中的疾病的方法，其包括对该个体施用治疗有效量的根据权利要求1-9任一项所述的抗体或其抗原结合片段或根据权利要求17所述的组合物。
  24. 根据权利要求23所述的方法，其中该疾病是下呼吸道感染。
  25. 如说明书所述的发明。
PCT/CN2023/137389 2022-12-08 2023-12-08 特异性结合rsv的抗体 WO2024120517A1 (zh)

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Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106496324A (zh) * 2015-11-30 2017-03-15 天津昊免生物技术有限公司 一种抗呼吸道合胞病毒的全人源抗体
US20170121394A1 (en) * 2015-10-29 2017-05-04 Merck Sharp & Dohme Corp. Antibody neutralizing human respiratory syncytial virus
CN110016079A (zh) * 2018-12-18 2019-07-16 珠海泰诺麦博生物技术有限公司 抗呼吸道合胞病毒的中和抗体及其应用
US20200239550A1 (en) * 2017-10-13 2020-07-30 Adimab, Llc Anti-respiratory syncytial virus antibodies, methods of their generation and use
CN111606993A (zh) * 2019-02-26 2020-09-01 中国科学院上海生命科学研究院 抗呼吸道合胞病毒的全人广谱中和抗体4f1及其应用
WO2021261762A1 (ko) * 2020-06-25 2021-12-30 재단법인 목암생명과학연구소 항-rsv 항체 및 이를 포함하는 약학적 조성물

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20020141990A1 (en) * 1996-11-01 2002-10-03 Smithkline Beecham Corporation Anti-RSV human monoclonal antibodies
US20050175986A1 (en) * 2000-05-09 2005-08-11 Smit Kline Beecham Corporation Human monoclonal antibody
JP2008513540A (ja) * 2004-09-21 2008-05-01 メディミューン，インコーポレーテッド 呼吸器合胞体ウイルスに対する抗体及び該ウイルス用のワクチンを製造する方法
CL2011003002A1 (es) * 2011-11-25 2012-05-25 Univ Pontificia Catolica Chile Anticuerpo monoclonal o un fragmento del mismo que se une a la proteina m2-1 del virus respiratorio sincicial (vrs) humano; secuencias nucleotidicas; composicion farmaceutica; metodo de diagnostico de infeccion producida por vrs; kit; y uso de dicho anticuerpo para preparar un medicamento.
TW202228779A (zh) * 2017-03-01 2022-08-01 英商梅迪繆思有限公司 抗rsv單株抗體配製物
CN113249333B (zh) * 2021-03-16 2023-06-02 贵州省人民医院 一种分泌抗呼吸道合胞病毒单克隆抗体的杂交瘤细胞株rsvn4c3

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20170121394A1 (en) * 2015-10-29 2017-05-04 Merck Sharp & Dohme Corp. Antibody neutralizing human respiratory syncytial virus
CN106496324A (zh) * 2015-11-30 2017-03-15 天津昊免生物技术有限公司 一种抗呼吸道合胞病毒的全人源抗体
US20200239550A1 (en) * 2017-10-13 2020-07-30 Adimab, Llc Anti-respiratory syncytial virus antibodies, methods of their generation and use
CN110016079A (zh) * 2018-12-18 2019-07-16 珠海泰诺麦博生物技术有限公司 抗呼吸道合胞病毒的中和抗体及其应用
CN111606993A (zh) * 2019-02-26 2020-09-01 中国科学院上海生命科学研究院 抗呼吸道合胞病毒的全人广谱中和抗体4f1及其应用
WO2021261762A1 (ko) * 2020-06-25 2021-12-30 재단법인 목암생명과학연구소 항-rsv 항체 및 이를 포함하는 약학적 조성물

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