AR126900A1 - GENETICALLY MODIFIED CORONAVIRUS POLYPEPTIDES, POLYNUCLEOTIDES, VECTORS AND HOST CELLS, AND RELATED COMPOSITIONS - Google Patents

GENETICALLY MODIFIED CORONAVIRUS POLYPEPTIDES, POLYNUCLEOTIDES, VECTORS AND HOST CELLS, AND RELATED COMPOSITIONS

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Publication number
AR126900A1
AR126900A1 ARP220102318A ARP220102318A AR126900A1 AR 126900 A1 AR126900 A1 AR 126900A1 AR P220102318 A ARP220102318 A AR P220102318A AR P220102318 A ARP220102318 A AR P220102318A AR 126900 A1 AR126900 A1 AR 126900A1
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AR
Argentina
Prior art keywords
seq
polypeptide
rbd
amino acid
acid sequence
Prior art date
Application number
ARP220102318A
Other languages
Spanish (es)
Inventor
Ann M Arvin
Normand Blais
Davide Corti
Colin Havenar-Daughton
Matteo Samuele Pizzuto
Lionel Sacconnay
Gyorgy Snell
Original Assignee
Humabs Biomed Sa
Vir Biotechnology Inc
Glaxosmithkline Biologicals Sa
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Publication date
Application filed by Humabs Biomed Sa, Vir Biotechnology Inc, Glaxosmithkline Biologicals Sa filed Critical Humabs Biomed Sa
Publication of AR126900A1 publication Critical patent/AR126900A1/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
    • 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
    • A61K39/12—Viral antigens
    • 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
    • A61K39/46—Cellular immunotherapy
    • A61K39/461—Cellular immunotherapy characterised by the cell type used
    • A61K39/4611—T-cells, e.g. tumor infiltrating lymphocytes [TIL], lymphokine-activated killer cells [LAK] or regulatory T cells [Treg]
    • 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
    • A61K39/46—Cellular immunotherapy
    • A61K39/463—Cellular immunotherapy characterised by recombinant expression
    • A61K39/4634—Antigenic peptides; polypeptides
    • 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
    • A61K39/46—Cellular immunotherapy
    • A61K39/464—Cellular immunotherapy characterised by the antigen targeted or presented
    • A61K39/464838—Viral antigens
    • 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
    • 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
    • C07K16/1002—Coronaviridae
    • C07K16/1003—Severe acute respiratory syndrome coronavirus 2 [SARS‐CoV‐2 or Covid-19]
    • 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
    • A61K2039/62—Medicinal preparations containing antigens or antibodies characterised by the link between antigen and carrier
    • A61K2039/627—Medicinal preparations containing antigens or antibodies characterised by the link between antigen and carrier characterised by the linker
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/34—Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
    • C07K2319/02—Fusion polypeptide containing a localisation/targetting motif containing a signal sequence
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/40—Fusion polypeptide containing a tag for immunodetection, or an epitope for immunisation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/70—Fusion polypeptide containing domain for protein-protein interaction
    • 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
    • C12N2770/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses positive-sense
    • C12N2770/00011—Details
    • C12N2770/20011—Coronaviridae
    • C12N2770/20022—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
    • 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
    • C12N2770/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses positive-sense
    • C12N2770/00011—Details
    • C12N2770/20011—Coronaviridae
    • C12N2770/20034—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
    • 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
    • C12N2770/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses positive-sense
    • C12N2770/00011—Details
    • C12N2770/36011—Togaviridae
    • C12N2770/36111—Alphavirus, e.g. Sindbis virus, VEE, EEE, WEE, Semliki
    • C12N2770/36141—Use of virus, viral particle or viral elements as a vector
    • C12N2770/36143—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector

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  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Virology (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Organic Chemistry (AREA)
  • Immunology (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Molecular Biology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Biophysics (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Epidemiology (AREA)
  • Genetics & Genomics (AREA)
  • Biochemistry (AREA)
  • Cell Biology (AREA)
  • Pulmonology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Communicable Diseases (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Oncology (AREA)
  • Peptides Or Proteins (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)

Abstract

Se proporcionan aquí polipéptidos de coronavirus de ingeniería, polinucleótidos que codifican los polipéptidos, vectores y células huésped que comprenden los polinucleótidos y/o expresan los polipéptidos, y composiciones relacionadas. Las formas de realización divulgadas incluyen, por ejemplo, ectodominios de espiga diseñados, dominios de unión a receptores monoméricos (RBD), RBD diseñados y proteínas de fusión que comprenden uno o más de los anteriores. Reivindicación 1: Una proteína de fusión que comprende un primer polipéptido de dominio de unión al receptor (RBD) de coronavirus unido a un segundo polipéptido RBD de coronavirus, en el que, opcionalmente, el primer y/o el segundo polipéptido RBD son de un betacoronavirus, y en el que, además, opcionalmente, el primer y el segundo polipéptido RBD son de diferentes betacoronavirus. Reivindicación 40: Un polipéptido aislado que comprende: (i) SEQ ID Nº 218; (ii) SEQ ID Nº 218 sin la SEQ ID Nº 706; (iii) SEQ ID Nº 712; (iv) SEQ ID Nº 712 sin SEQ ID Nº 706; (v) SEQ ID Nº 713; (vi) SEQ ID Nº 713 sin la SEQ ID Nº 706; (vii) SEQ ID Nº 714; (viii) SEQ ID Nº 714 sin la SEQ ID Nº 706; (ix) SEQ ID Nº 715; (x) SEQ ID Nº 715 sin la SEQ ID Nº 706; (xi) SEQ ID Nº 716; (xii) SEQ ID Nº 716 sin la SEQ ID Nº 706; (xiii) SEQ ID Nº 717; (xiv) SEQ ID Nº 717 sin la SEQ ID Nº 706; (xv) SEQ ID Nº 738; (xvi) SEQ ID Nº 739; (xvii) SEQ ID Nº 740; (xviii) SEQ ID Nº 741; (xix) SEQ ID Nº 742; o (xx) SEQ ID Nº 743. Reivindicación 42: Una proteína de fusión que comprende un polipéptido del dominio de unión al receptor (RBD) del coronavirus y uno o ambos de (i) y (ii), (i) una o más etiquetas peptídicas; (ii) uno o más polipéptidos de tallo-hélice, en los que, opcionalmente, el uno o más polipéptidos de tallo-hélice comprenden o consisten en la secuencia de aminoácidos PGSFKEELDKYFKNHTSDAASKAGP (SEQ ID Nº 701). Reivindicación 57: Un polipéptido aislado que comprende una estructura RBD1 - L1 - RBD2 - L2 - RBD3 - L3 - RBD4 - L4 - RBD5 en donde RBD1, RBD2, RBD3, RBD4 y RBD5 son cada uno un polipéptido RBD diferente seleccionado del grupo que consiste en: variante Beta del SARS-CoV-2; variante Omicron del SARS-CoV-2; variante Delta del SARS-CoV-2; PANG/GX; MP789; RaTG13; y RsSHC014, en donde RBD1 es el polipéptido RBD N-terminal de la proteína de fusión y/o RBD5 es el polipéptido RBD C-terminal de la proteína de fusión, y en donde L1, L2, L3 y L4 son cada uno un enlazador. Reivindicación 63: Un polipéptido aislado que comprende o consiste en la secuencia de aminoácidos de cualquiera de las SEQ ID Nº 701, 4 - 19, 46 y 57 - 59. Reivindicación 64: Un polipéptido aislado que comprende o consiste en la secuencia de aminoácidos de SEQ ID Nº 701, la secuencia de aminoácidos de SEQ ID Nº 14, la secuencia de aminoácidos de SEQ ID Nº 15, la secuencia de aminoácidos de SEQ ID Nº 16, o la secuencia de aminoácidos de SEQ ID Nº 17. Reivindicación 65: Un polinucleótido aislado que codifica la proteína de fusión de acuerdo con cualquiera de las reivindicaciones 1 - 39 y 42 - 56, o el polipéptido de acuerdo con cualquiera de las reivindicaciones 40, 41 y 57 - 64. Reivindicación 72: Un método para tratar, o para inducir una respuesta inmunitaria contra una infección por coronavirus en un sujeto, el método comprende administrar al sujeto una cantidad eficaz de: la proteína de fusión de acuerdo con cualquiera de las reivindicaciones 1 - 39 y 42 - 56; el polipéptido de acuerdo con cualquiera de las reivindicaciones 40, 41 y 57 - 64; el polinucleótido de acuerdo con cualquiera de las reivindicaciones 65 - 67; el vector de acuerdo con la reivindicación 68; la célula huésped de acuerdo con la reivindicación 69; o la composición de acuerdo con la reivindicación 70 o 71, en donde, opcionalmente, la infección por coronavirus comprende una infección por sarbecovirus.Provided herein are engineered coronavirus polypeptides, polynucleotides encoding the polypeptides, vectors and host cells comprising the polynucleotides and/or expressing the polypeptides, and related compositions. Disclosed embodiments include, for example, engineered spike ectodomains, monomeric receptor binding domains (RBDs), engineered RBDs, and fusion proteins comprising one or more of the above. Claim 1: A fusion protein comprising a first coronavirus receptor binding domain (RBD) polypeptide linked to a second coronavirus RBD polypeptide, wherein, optionally, the first and/or the second RBD polypeptide are from a betacoronavirus, and wherein further, optionally, the first and second RBD polypeptides are from different betacoronaviruses. Claim 40: An isolated polypeptide comprising: (i) SEQ ID NO: 218; (ii) SEQ ID No. 218 without SEQ ID No. 706; (iii) SEQ ID NO: 712; (iv) SEQ ID NO: 712 without SEQ ID NO: 706; (v) SEQ ID NO: 713; (vi) SEQ ID No. 713 without SEQ ID No. 706; (vii) SEQ ID NO: 714; (viii) SEQ ID No. 714 without SEQ ID No. 706; (ix) SEQ ID NO: 715; (x) SEQ ID NO: 715 without SEQ ID NO: 706; (xi) SEQ ID NO: 716; (xii) SEQ ID NO: 716 without SEQ ID NO: 706; (xiii) SEQ ID NO: 717; (xiv) SEQ ID No. 717 without SEQ ID No. 706; (xv) SEQ ID NO: 738; (xvi) SEQ ID NO: 739; (xvii) SEQ ID NO: 740; (xviii) SEQ ID NO: 741; (xix) SEQ ID NO: 742; or (xx) SEQ ID NO: 743. Claim 42: A fusion protein comprising a coronavirus receptor binding domain (RBD) polypeptide and one or both of (i) and (ii), (i) one or more peptide tags; (ii) one or more stem-helix polypeptides, wherein, optionally, the one or more stem-helix polypeptides comprise or consist of the amino acid sequence PGSFKEELDKYFKNHTSDAASKAGP (SEQ ID NO: 701). Claim 57: An isolated polypeptide comprising a structure RBD1 - L1 - RBD2 - L2 - RBD3 - L3 - RBD4 - L4 - RBD5 wherein RBD1, RBD2, RBD3, RBD4 and RBD5 are each a different RBD polypeptide selected from the group consisting in: Beta variant of SARS-CoV-2; Omicron variant of SARS-CoV-2; Delta variant of SARS-CoV-2; PANG/GX; MP789; RaTG13; and RsSHC014, wherein RBD1 is the N-terminal RBD polypeptide of the fusion protein and/or RBD5 is the C-terminal RBD polypeptide of the fusion protein, and wherein L1, L2, L3 and L4 are each a linker . Claim 63: An isolated polypeptide comprising or consisting of the amino acid sequence of any of SEQ ID NO: 701, 4-19, 46 and 57-59. Claim 64: An isolated polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 701, the amino acid sequence of SEQ ID NO: 14, the amino acid sequence of SEQ ID NO: 15, the amino acid sequence of SEQ ID NO: 16, or the amino acid sequence of SEQ ID NO: 17. Claim 65: A Isolated polynucleotide encoding the fusion protein according to any of claims 1-39 and 42-56, or the polypeptide according to any of claims 40, 41 and 57-64. Claim 72: A method of treating, or to induce an immune response against a coronavirus infection in a subject, the method comprises administering to the subject an effective amount of: the fusion protein according to any of claims 1-39 and 42-56; the polypeptide according to any of claims 40, 41 and 57-64; the polynucleotide according to any of claims 65-67; the vector according to claim 68; the host cell according to claim 69; or the composition according to claim 70 or 71, wherein, optionally, the coronavirus infection comprises a sarbecovirus infection.

ARP220102318A 2021-08-27 2022-08-26 GENETICALLY MODIFIED CORONAVIRUS POLYPEPTIDES, POLYNUCLEOTIDES, VECTORS AND HOST CELLS, AND RELATED COMPOSITIONS AR126900A1 (en)

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Publication number Priority date Publication date Assignee Title
AU2021306709A1 (en) 2020-07-06 2023-02-09 Flagship Pioneering Innovations Vi, Llc Antigen binding molecules targeting SARS-CoV-2
IL300720A (en) 2020-08-26 2023-04-01 Flagship Pioneering Innovations Vi Llc Antigen binding molecules targeting sars-cov-2

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