HRP20231066T1 - Bcma (cd269/tnfrsf17) - vezujući proteini - Google Patents
Bcma (cd269/tnfrsf17) - vezujući proteini Download PDFInfo
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- HRP20231066T1 HRP20231066T1 HRP20231066TT HRP20231066T HRP20231066T1 HR P20231066 T1 HRP20231066 T1 HR P20231066T1 HR P20231066T T HRP20231066T T HR P20231066TT HR P20231066 T HRP20231066 T HR P20231066T HR P20231066 T1 HRP20231066 T1 HR P20231066T1
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- antibody
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- 102000014914 Carrier Proteins Human genes 0.000 title 1
- 101100425747 Mus musculus Tnfrsf17 gene Proteins 0.000 title 1
- 108091008324 binding proteins Proteins 0.000 title 1
- 229940127121 immunoconjugate Drugs 0.000 claims 10
- MFRNYXJJRJQHNW-DEMKXPNLSA-N (2s)-2-[[(2r,3r)-3-methoxy-3-[(2s)-1-[(3r,4s,5s)-3-methoxy-5-methyl-4-[methyl-[(2s)-3-methyl-2-[[(2s)-3-methyl-2-(methylamino)butanoyl]amino]butanoyl]amino]heptanoyl]pyrrolidin-2-yl]-2-methylpropanoyl]amino]-3-phenylpropanoic acid Chemical compound CN[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N(C)[C@@H]([C@@H](C)CC)[C@H](OC)CC(=O)N1CCC[C@H]1[C@H](OC)[C@@H](C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 MFRNYXJJRJQHNW-DEMKXPNLSA-N 0.000 claims 7
- 102000006942 B-Cell Maturation Antigen Human genes 0.000 claims 7
- 108010008014 B-Cell Maturation Antigen Proteins 0.000 claims 7
- 108010059074 monomethylauristatin F Proteins 0.000 claims 7
- 229940127089 cytotoxic agent Drugs 0.000 claims 6
- 239000002254 cytotoxic agent Substances 0.000 claims 6
- 231100000599 cytotoxic agent Toxicity 0.000 claims 6
- 150000007523 nucleic acids Chemical group 0.000 claims 6
- 206010035226 Plasma cell myeloma Diseases 0.000 claims 4
- -1 6-maleimidocaproyl Chemical group 0.000 claims 3
- 208000037914 B-cell disorder Diseases 0.000 claims 3
- 210000004027 cell Anatomy 0.000 claims 3
- 238000000034 method Methods 0.000 claims 3
- BQWBEDSJTMWJAE-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 4-[(2-iodoacetyl)amino]benzoate Chemical compound C1=CC(NC(=O)CI)=CC=C1C(=O)ON1C(=O)CCC1=O BQWBEDSJTMWJAE-UHFFFAOYSA-N 0.000 claims 2
- 208000017604 Hodgkin disease Diseases 0.000 claims 2
- 208000021519 Hodgkin lymphoma Diseases 0.000 claims 2
- 208000010747 Hodgkins lymphoma Diseases 0.000 claims 2
- 206010021245 Idiopathic thrombocytopenic purpura Diseases 0.000 claims 2
- 102100029193 Low affinity immunoglobulin gamma Fc region receptor III-A Human genes 0.000 claims 2
- 101710099301 Low affinity immunoglobulin gamma Fc region receptor III-A Proteins 0.000 claims 2
- 208000034578 Multiple myelomas Diseases 0.000 claims 2
- 206010053869 POEMS syndrome Diseases 0.000 claims 2
- 208000031981 Thrombocytopenic Idiopathic Purpura Diseases 0.000 claims 2
- IEDXPSOJFSVCKU-HOKPPMCLSA-N [4-[[(2S)-5-(carbamoylamino)-2-[[(2S)-2-[6-(2,5-dioxopyrrolidin-1-yl)hexanoylamino]-3-methylbutanoyl]amino]pentanoyl]amino]phenyl]methyl N-[(2S)-1-[[(2S)-1-[[(3R,4S,5S)-1-[(2S)-2-[(1R,2R)-3-[[(1S,2R)-1-hydroxy-1-phenylpropan-2-yl]amino]-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl]-3-methoxy-5-methyl-1-oxoheptan-4-yl]-methylamino]-3-methyl-1-oxobutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]-N-methylcarbamate Chemical group CC[C@H](C)[C@@H]([C@@H](CC(=O)N1CCC[C@H]1[C@H](OC)[C@@H](C)C(=O)N[C@H](C)[C@@H](O)c1ccccc1)OC)N(C)C(=O)[C@@H](NC(=O)[C@H](C(C)C)N(C)C(=O)OCc1ccc(NC(=O)[C@H](CCCNC(N)=O)NC(=O)[C@@H](NC(=O)CCCCCN2C(=O)CCC2=O)C(C)C)cc1)C(C)C IEDXPSOJFSVCKU-HOKPPMCLSA-N 0.000 claims 2
- 125000003275 alpha amino acid group Chemical group 0.000 claims 2
- 201000003710 autoimmune thrombocytopenic purpura Diseases 0.000 claims 2
- 239000012636 effector Substances 0.000 claims 2
- 239000013604 expression vector Substances 0.000 claims 2
- 201000007919 lymphoplasmacytic lymphoma Diseases 0.000 claims 2
- 230000001404 mediated effect Effects 0.000 claims 2
- 108010093470 monomethyl auristatin E Proteins 0.000 claims 2
- 201000000050 myeloid neoplasm Diseases 0.000 claims 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 2
- JJAHTWIKCUJRDK-UHFFFAOYSA-N succinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate Chemical compound C1CC(CN2C(C=CC2=O)=O)CCC1C(=O)ON1C(=O)CCC1=O JJAHTWIKCUJRDK-UHFFFAOYSA-N 0.000 claims 2
- 201000000596 systemic lupus erythematosus Diseases 0.000 claims 2
- AGGWFDNPHKLBBV-YUMQZZPRSA-N (2s)-2-[[(2s)-2-amino-3-methylbutanoyl]amino]-5-(carbamoylamino)pentanoic acid Chemical compound CC(C)[C@H](N)C(=O)N[C@H](C(O)=O)CCCNC(N)=O AGGWFDNPHKLBBV-YUMQZZPRSA-N 0.000 claims 1
- AFZIRBOYYNKYFJ-UHFFFAOYSA-N 4-pyridin-2-ylsulfanylpentanoic acid Chemical compound OC(=O)CCC(C)SC1=CC=CC=N1 AFZIRBOYYNKYFJ-UHFFFAOYSA-N 0.000 claims 1
- 208000023761 AL amyloidosis Diseases 0.000 claims 1
- OMNVYXHOSHNURL-WPRPVWTQSA-N Ala-Phe Chemical compound C[C@H](N)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 OMNVYXHOSHNURL-WPRPVWTQSA-N 0.000 claims 1
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 claims 1
- 208000028564 B-cell non-Hodgkin lymphoma Diseases 0.000 claims 1
- 206010053177 Epidermolysis Diseases 0.000 claims 1
- 206010018366 Glomerulonephritis acute Diseases 0.000 claims 1
- 208000024869 Goodpasture syndrome Diseases 0.000 claims 1
- 208000005531 Immunoglobulin Light-chain Amyloidosis Diseases 0.000 claims 1
- 208000022435 Light chain deposition disease Diseases 0.000 claims 1
- 206010034277 Pemphigoid Diseases 0.000 claims 1
- 241000721454 Pemphigus Species 0.000 claims 1
- 208000007452 Plasmacytoma Diseases 0.000 claims 1
- 206010036673 Primary amyloidosis Diseases 0.000 claims 1
- 208000004346 Smoldering Multiple Myeloma Diseases 0.000 claims 1
- 208000033559 Waldenström macroglobulinemia Diseases 0.000 claims 1
- 231100000851 acute glomerulonephritis Toxicity 0.000 claims 1
- 108010011559 alanylphenylalanine Proteins 0.000 claims 1
- 210000000988 bone and bone Anatomy 0.000 claims 1
- 229960002173 citrulline Drugs 0.000 claims 1
- 201000003278 cryoglobulinemia Diseases 0.000 claims 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 1
- 208000035475 disorder Diseases 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 208000025750 heavy chain disease Diseases 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 201000005328 monoclonal gammopathy of uncertain significance Diseases 0.000 claims 1
- 208000015270 non-secretory plasma cell myeloma Diseases 0.000 claims 1
- 201000009234 osteosclerotic myeloma Diseases 0.000 claims 1
- 239000000825 pharmaceutical preparation Substances 0.000 claims 1
- 208000031223 plasma cell leukemia Diseases 0.000 claims 1
- 208000010721 smoldering plasma cell myeloma Diseases 0.000 claims 1
- 239000013598 vector Substances 0.000 claims 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2878—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
- A61K47/6803—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
- A61K47/6811—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being a protein or peptide, e.g. transferrin or bleomycin
- A61K47/6817—Toxins
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6835—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
- A61K47/6849—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a receptor, a cell surface antigen or a cell surface determinant
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
-
- 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
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
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- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
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- C07—ORGANIC CHEMISTRY
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- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/33—Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
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- C07K2317/00—Immunoglobulins specific features
- C07K2317/40—Immunoglobulins specific features characterized by post-translational modification
- C07K2317/41—Glycosylation, sialylation, or fucosylation
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- C07—ORGANIC CHEMISTRY
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- C07K2317/00—Immunoglobulins specific features
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- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/565—Complementarity determining region [CDR]
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- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/567—Framework region [FR]
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- C07—ORGANIC CHEMISTRY
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- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/72—Increased effector function due to an Fc-modification
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- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
- C07K2317/732—Antibody-dependent cellular cytotoxicity [ADCC]
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- C07—ORGANIC CHEMISTRY
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- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
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- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/77—Internalization into the cell
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- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
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- Proteomics, Peptides & Aminoacids (AREA)
- Genetics & Genomics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Toxicology (AREA)
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- Pain & Pain Management (AREA)
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- Rheumatology (AREA)
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- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Claims (21)
1. Protutijelo protiv antigena sazrijevanja B-stanica (CD269) koje sadrži varijabilnu regiju teškog lanca SEQ ID NO:23 i varijabilnu regiju lakog lanca SEQ ID NO:31.
2. Protutijelo protiv antigena sazrijevanja B-stanica (CD269) prema zahtjevu 1, naznačeno time što sadrži teški lanac iz SEQ ID NO:55 i laki lanac iz SEQ ID NO:63.
3. Protutijelo protiv antigena sazrijevanja B-stanica (CD269) prema bilo kojem prethodnom zahtjevu, naznačeno time što je protutijelo monoklonsko protutijelo.
4. Protutijelo protiv antigena sazrijevanja B-stanica (CD269) prema bilo kojem prethodnom zahtjevu, naznačeno time da protutijelo ima pojačano vezanje na FcyRIIIA ili ima pojačanu efektorsku funkciju posredovanu sa FcyRIIIA.
5. Protutijelo protiv antigena sazrijevanja B-stanica (CD269) prema zahtjevu 4, naznačeno time što je protutijelo defukozilirano.
6. Sekvence nukleinske kiseline koje kodiraju varijabilne sekvence teškog lanca i varijabilne sekvence lakog lanca protutijela prema bilo kojem prethodnom zahtjevu.
7. Sekvence nukleinske kiseline koje sadrže SEQ ID NO:56 koja kodira teški lanac; i SEQ ID NO:64 koji kodira laki lanac protutijela prema bilo kojem prethodnom zahtjevu.
8. Ekspresijski vektor koji sadrži sekvence nukleinske kiseline prema zahtjevu 6 ili zahtjevu 7.
9. Rekombinantno transformirana ili transfektirana stanica domaćina, naznačena time što sadrži sekvence nukleinske kiseline prema zahtjevu 6 ili zahtjevu 7, ili ekspresijski vektor prema zahtjevu 8, naznačena time što stanica domaćina sadrži sekvence nukleinske kiseline koje kodiraju i teške i lake lance.
10. Postupak za proizvodnju protutijela, naznačen time što postupak obuhvaća uzgoj stanice domaćina prema zahtjevu 9 pod uvjetima prikladnim za ekspresiju navedenih sekvenci nukleinskih kiselina ili vektora, pri čemu se proizvodi protutijelo.
11. Protutijelo kako je proizvedeno postupkom prema zahtjevu 10.
12. Imunokonjugat, naznačen time što sadrži protutijelo prema bilo kojem zahtjevu 1 do 5 ili zahtjevu 11 i citotoksično sredstvo.
13. Imunokonjugat prema zahtjevu 12, naznačen time što je citotoksično sredstvo monometil auristatin E (MMAE) ili monometil auristatin F (MMAF).
14. Imunokonjugat prema zahtjevu 13, naznačen time što je citotoksično sredstvo monometil auristatin F (MMAF).
15. Imunokonjugat prema bilo kojem od zahtjeva 12-14, naznačen time što je protutijelo povezano na citotoksično sredstvo preko poveznice.
16. Imunokonjugat prema zahtjevu 15, naznačen time što je poveznica odabrana između 6-maleimidokaproila (MC), maleimidopropanoila (MP), valin-citrulina (val-cit), alanin-fenilalanina (ala-phe), paminobenziloksikarbonila (PAB), N-sukcinimidil 4-(2-piridiltio)pentanoata (SPP), N-sukcinimidil 4-(N-maleimidometil)cikloheksan-1-karboksilata (SMCC), i N-sukcinimidil (4-jodo-acetil) aminobenzoata (SIAB).
17. Imunokonjugat prema zahtjevu 16, naznačen time što je poveznica 6-maleimidokaproil (MC).
18. Imunokonjugat koji sadrži protutijelo protiv antigena sazrijevanja B-stanica (CD269) i citotoksično sredstvo pri čemu protutijelo protiv antigena sazrijevanja B-stanica (CD269) ima pojačano vezanje na FcyRIIIA ili ima pojačanu efektorsku funkciju posredovanu FcyRIIIA i sadrži aminokiselinsku sekvencu teškog lanca prema SEQ ID NO:55 i aminokiselinsku sekvencu lakog lanca prema SEQ ID NO:63, te pri čemu je antitijelo defukozilirano i pri čemu je citotoksično sredstvo monometil auristatin F (MMAF) i pri čemu je navedeni MMAF vezan za navedeno protutijelo preko poveznice 6-maleimidokaproil (MC).
19. Farmaceutski pripravak, naznačen time što sadrži protutijelo prema bilo kojem od zahtjeva 1-5 ili prema zahtjevu 11 ili imunokonjugat prema bilo kojem od zahtjeva 12-18 i farmaceutski prihvatljiv nosač.
20. Protutijelo prema bilo kojem od zahtjeva 1-5 i 11, imunokonjugat prema bilo kojem od zahtjeva 12-18, ili farmaceutski pripravak prema zahtjevu 19 za upotrebu u liječenju ljudskog pacijenta koji boluje od bolesti B-stanica ili poremećaja odabranog od multiplog mijeloma (MM), kronične limfocitne leukemije (CLL), nesekretornog multiplog mijeloma, tinjajućeg multiplog mijeloma, monoklonske gamapatije neodređenog značaja (MGUS), solitarnog plazmocitoma (koštani, ekstramedularni), limfoplazmocitnog limfoma (LPL), Waldenstromove makroglobulinemije, leukemije plazma stanica, primarne amiloidoze (AL), bolesti teških lanaca, sistemskog eritematoznog lupusa (SLE), POEMS sindroma I osteosklerotičnog mijeloma, krioglobulinemije tipa I i II, bolesti taloženja lakih lanaca, Goodpastureovog sindroma, idiopatske trombocitopenične purpure (ITP), akutnog glomerulonefritisa, pemfigusa i pemfigoidnih poremećaja, i stečene bulozne epidermolize; ili bilo kojeg ne-Hodgkinovog limfoma leukemije B-stanica ili Hodgkinovog limfoma (HL).
21. Protutijelo, imunokonjugat ili farmaceutski pripravak za upotrebu prema zahtjevu 20, naznačen time što je bolest B-stanica multipli mijelom (MM).
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