WO2021148884A1 - Anticorps anti-coronavirus du wuhan - Google Patents

Anticorps anti-coronavirus du wuhan Download PDF

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Publication number
WO2021148884A1
WO2021148884A1 PCT/IB2021/000031 IB2021000031W WO2021148884A1 WO 2021148884 A1 WO2021148884 A1 WO 2021148884A1 IB 2021000031 W IB2021000031 W IB 2021000031W WO 2021148884 A1 WO2021148884 A1 WO 2021148884A1
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Prior art keywords
antibody
antigen
binding fragment
antibodies
cov
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PCT/IB2021/000031
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English (en)
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Yadunanda Kumar BUDIGI
Debbie Ching Ping LEE
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Tychan Pte. Ltd.
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Publication of WO2021148884A1 publication Critical patent/WO2021148884A1/fr

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    • 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]
    • 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

Definitions

  • the Wuhan coronavirus is a novel coronavirus that belongs to the member of the coronavirus family, which also includes the SARS-CoV, MERS-CoV and others. Viruses belonging to this family are known to primarily infect the upper respiratory and gastrointestinal tract of mammals and birds. First reported in the Wuhan seafood market in later part of 2019, Wu-CoV has now caused 517 cases of human infection and 17 deaths in China alone, with recent evidence confirming human-to-human transmission. Other countries such as Singapore, US, Japan, Taiwan, South Korea, and Thailand have also confirmed cases of Wu-CoV infection. There are no approved vaccines or therapies against the virus.
  • coronaviruses As disclosed herein, the overall structure of coronaviruses is governed by four key proteins: spike (S), envelope (E), membrane (M) and nucleocapsid (N).
  • S spike
  • E envelope
  • M membrane
  • N nucleocapsid
  • the spike protein attaches to the host receptor and mediates viral entry through fusion. Binding to spike protein to prevent viral entry is an effective mechanism for antibody-based neutralization of Co Vs.
  • provided herein are antibodies and antigen binding fragments thereof against the RBD of Wu-CoV. In some aspects, provided herein are methods of treating or preventing Wu-CoV infection using the antibodies provided herien. In certain aspects, provided herein are nucleic acid molecules encoding the antibodies provided herein, as well as host cells comprising such nucleic acids, and methods of making the antibodies provided herein using such host cells. In some aspects, also provided herein are pharmaceutical compositions comprising the antibodies provided herein. DETAILED DESCRIPTION
  • isolated antibodies particularly monoclonal antibodies, which specifically bind to the RBD of Wu-CoV. Accordingly, provided herein are isolated antibodies, methods of making such antibodies, method of diagnosing for Wu-CoV infection, preventing Wu-CoV infection, treating Wu-CoV infection, and pharmaceutical compositions formulated to contain the antibodies.
  • the antibodies provided herein comprise a heavy chain variable region sequence listed in Table 1 (SEQ ID NOS: 1-77).
  • the antibodies provided herein have an amino acid sequence that is at least 90% identical ⁇ e-g ⁇ , at least 91% identical, at least 92% identical, at least 93% identical, at least 94% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, at least 99% identical, and/or 100% identical) to an amino acid sequence listed in Table 1.
  • the antibodies provided herein comprise a light chain variable region sequence listed in Table 2 (SEQ ID NOS: 78-122).
  • the antibodies provided herein have an amino acid sequence that is at least 90% identical (e.g., at least 91% identical, at least 92% identical, at least 93% identical, at least 94% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, at least 99% identical, and/or 100% identical) to an amino acid sequence listed in Table 2.
  • the antibodies provided herein comprise a IgGl heavy chain constant region sequence listed in Table 3 (SEQ ID NO: 123).
  • the antibodies provided herein have an amino acid sequence that is at least 90% identical (e.g, at least 91% identical, at least 92% identical, at least 93% identical, at least 94% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, at least 99% identical, and/or 100% identical) to an amino acid sequence listed in Table 3.
  • the antibodies provided herein comprise a IgGl heavy chain constant region sequence with Met-252-Tyr, Ser-254-Thr and Thr-256-Glu substitutions (substitutions at residues corresponding to methionine 252, serine 254 and threonine 256, each in EU numbering) listed in Table 4 (SEQ ID NO: 124).
  • the antibodies provided herein have an amino acid sequence that is at least 90% identical (e.g, at least 91% identical, at least 92% identical, at least 93% identical, at least 94% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, at least 99% identical, and/or 100% identical) to an amino acid sequence listed in Table 4.
  • the antibodies provided herein exhibit an enhanced half-life
  • antibody as used to herein includes whole antibodies and any antigen binding fragments (i.e., “antigen-binding portions”) or single chains thereof.
  • An “antibody” refers, in one embodiment, to a glycoprotein comprising at least two heavy (H) chains and two light (L) chains inter-connected by disulfide bonds, or an antigen binding portion thereof.
  • Each heavy chain is comprised of a heavy chain variable region (abbreviated herein as VH) and a heavy chain constant region.
  • VH heavy chain variable region
  • L light chain constant region
  • each light chain is comprised of a light chain variable region (abbreviated herein as VL) and a light chain constant region.
  • the light chain constant region is comprised of one domain, CL.
  • the VH and VL regions can be further subdivided into regions of hypervariability, termed complementarity determining regions (CDR), interspersed with regions that are more conserved, termed framework regions (FR).
  • CDR complementarity determining regions
  • FR framework regions
  • Each VH and VL is composed of three CDRs and four FRs, arranged from amino-terminus to carboxy-terminus in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4.
  • the variable regions of the heavy and light chains contain a binding domain that interacts with an antigen.
  • the constant regions of the antibodies may mediate the binding of the immunoglobulin to host tissues or factors, including various cells of the immune system (e.g ., effector cells) and the first component (Clq) of the classical complement system.
  • Antibodies typically bind specifically to their cognate antigen with high affinity, reflected by a dissociation constant (KD) of 10 5 to 10 11 M or less. Any KD greater than about 10 4 M is generally considered to indicate nonspecific binding.
  • KD dissociation constant
  • an antibody that "binds specifically" to an antigen refers to an antibody that binds to the antigen and substantially identical antigens with high affinity, which means having a KD of 10 7 M or less, preferably 10 8 M or less, even more preferably 5 x 10 9 M or less, and most preferably between 10 8 M and 10 10 M or less, but does not bind with high affinity to unrelated antigens.
  • An antigen is "substantially identical" to a given antigen if it exhibits a high degree of sequence identity to the given antigen, for example, if it exhibits at least 80%, at least 90%, preferably at least 95%, more preferably at least 97%, or even more preferably at least 99% sequence identity to the sequence of the given antigen.
  • the antibodies provided herein may be from any of the commonly known isotypes, including but not limited to IgA, secretory IgA, IgG and IgM.
  • the IgG isotype is divided in subclasses in certain species: IgGl, IgG2, IgG3 and IgG4 in humans, and IgGl, IgG2a, IgG2b and IgG3 in mice.
  • Immunoglobulins, e.g. , IgGl exist in several allotypes, which differ from each other in at most a few amino acids.
  • Antibody includes, by way of example, both naturally occurring and non-naturally occurring antibodies; monoclonal and polyclonal antibodies; chimeric and humanized antibodies; human and nonhuman antibodies; wholly synthetic antibodies; and single chain antibodies.
  • antigen-binding portions of antibodies disclosed herein are antigen-binding portions of antibodies disclosed herein.
  • the term “antigen-binding portion” of an antibody refers to one or more fragments of an antibody that retain the ability to specifically bind to an antigen (e.g., the RBD of Wu-CoV).
  • fragments are, for example between about 8 and about 1500 amino acids in length, suitably between about 8 and about 745 amino acids in length, suitably about 8 to about 300, for example about 8 to about 200 amino acids, or about 10 to about 50 or 100 amino acids in length. It has been shown that the antigen binding function of an antibody can be performed by fragments of a full-length antibody.
  • binding fragments encompassed within the term “antigen-binding portion” of an antibody, described herein, include (i) a Fab fragment, a monovalent fragment consisting of the VL, VH, CL and CHI domains; (ii) a F(ab')2 fragment, a bivalent fragment comprising two Fab fragments linked by a disulfide bridge at the hinge region; (iii) a Fd fragment consisting of the VH and CHI domains; (iv) a Fv fragment consisting of the VL and VH domains of a single arm of an antibody, (v) a dAb fragment (Ward et al.
  • Antigen-binding portions can be produced by recombinant DNA techniques, or by enzymatic or chemical cleavage of intact immunoglobulins.
  • the antibodies provided herein comprise one or more CDRs of antibodies provided herein (e.g, antibodies with heavy and light chain variable regions provided in Tables 1 and 2, respectively)
  • CDRs are amino acid residues within the hypervariable region that are identified in accordance with the definitions of the Rabat, Chothia, AbM, contact, and/or conformational definitions or any method of CDR determination well known in the art.
  • Antibody CDRs may be identified as the hypervariable regions originally defined by Rabat et al. See, e.g. , Rabat et al., 1992, Sequences of Proteins of Immunological Interest, 5th ed., Public Health Service, NIH, Washington D.C.
  • the positions of the CDRs may also be identified as the structural loop structures originally described by Chothia and others. See, e.g, Chothia et al., 1989, Nature 342:877-883.
  • Other approaches to CDR identification include the “AbM definition,” which is a compromise between Rabat and Chothia and is derived using Oxford Molecular's AbM antibody modeling software (now Accelrys®), or the “contact definition” of CDRs based on observed antigen contacts, set forth in MacCallum et al., 1996, J. Mol. Biol., 262:732-745.
  • CDRs In another approach, referred to herein as the “conformational definition” of CDRs, the positions of the CDRs may be identified as the residues that make enthalpic contributions to antigen binding. See, e.g ., Makabe et al., 2008, Journal of Biological Chemistry, 283:1156- 1166. Still other CDR boundary definitions may not strictly follow one of the above approaches, but will nonetheless overlap with at least a portion of the Rabat CDRs, although they may be shortened or lengthened in light of prediction or experimental findings that particular residues or groups of residues or even entire CDRs do not significantly impact antigen binding. As used herein, a CDR may refer to CDRs defined by any approach known in the art, including combinations of approaches.
  • CDRs defined according to any of these approaches.
  • the CDRs may be defined in accordance with any of Rabat, Chothia, extended, AbM, contact, and/or conformational definitions.
  • the antibodies provided herein are monoclonal antibodies.
  • the term “monoclonal antibody,” as used herein, refers to an antibody that displays a single binding specificity and affinity for a particular epitope or a composition of antibodies in which all antibodies display a single binding specificity and affinity for a particular epitope.
  • the term “human monoclonal antibody” refers to an antibody or antibody composition that display(s) a single binding specificity and which has variable and optional constant regions derived from human germline immunoglobulin sequences.
  • human monoclonal antibodies are produced by a hybridoma which includes a B cell obtained from a transgenic non-human animal, e.g. , a transgenic mouse, having a genome comprising a human heavy chain transgene and a light chain transgene fused to an immortalized cell.
  • the antibodies provided herein are humanized antibodies.
  • a “humanized” antibody refers to an antibody in which some, most or all of the amino acids outside the CDR domains of a non-human antibody are replaced with corresponding amino acids derived from human immunoglobulins. In one embodiment of a humanized form of an antibody, some, most or all of the amino acids outside the CDR domains have been replaced with amino acids from human immunoglobulins, whereas some, most or all amino acids within one or more CDR regions are unchanged. Small additions, deletions, insertions, substitutions or modifications of amino acids are permissible as long as they do not abrogate the ability of the antibody to bind to a particular antigen.
  • a “humanized” antibody retains an antigenic specificity similar to that of the original antibody.
  • the antibodies provided herein are chimeric antibodies.
  • a “chimeric antibody” refers to an antibody in which the variable regions are derived from one species and the constant regions are derived from another species, such as an antibody in which the variable regions are derived from a mouse antibody and the constant regions are derived from a human antibody.
  • the antibodies provided herein can be of any isotype.
  • isotype refers to the antibody class (e.g ., IgGl, IgG2, IgG3, IgG4, IgM,
  • the antibodies provided herein are IgGl, IgG2, IgG3, IgG4, IgM, IgAl, IgA2, IgD, or IgE isotype antibodies.
  • an “Fc region” fragment crystallizable region or “Fc domain” or “Fc” refers to the C -terminal region of the heavy chain of an antibody that mediates the binding of the immunoglobulin to host tissues or factors, including binding to Fc receptors located on various cells of the immune system (e.g., effector cells) or to the first component (Clq) of the classical complement system.
  • an Fc region comprises the constant region of an antibody excluding the first constant region immunoglobulin domain (e.g, CHI or CL).
  • the Fc region comprises two identical protein fragments, derived from the second (Cm) and third (Cm) constant domains of the antibody’s two heavy chains; IgM and IgE Fc regions comprise three heavy chain constant domains (CH domains 2-4) in each polypeptide chain.
  • the Fc region comprises immunoglobulin domains Cy2 and Cy3 and the hinge between Cyl and Cy2.
  • the human IgG heavy chain Fc region is usually defined to stretch from an amino acid residue at position C226 or P230 (or amino acid between these two amino acids) to the carboxy -terminus of the heavy chain, wherein the numbering is according to the EU index as in Kabat.
  • the Cm domain of a human IgG Fc region extends from about amino acid 231 to about amino acid 340, whereas the Cm domain is positioned on C-terminal side of a Cm domain in an Fc region, i.e., it extends from about amino acid 341 to about amino acid 447 of an IgG.
  • the Fc region may be a native sequence Fc, including any allotypic variant, or a variant Fc (e.g, a non-naturally occurring Fc).
  • Fc may also refer to this region in isolation or in the context of an Fc-comprising protein polypeptide such as a “binding protein comprising an Fc region,” also referred to as an “Fc fusion protein” (e.g., an antibody or immunoadhesin).
  • a “native sequence Fc region” or “native sequence Fc” comprises an amino acid sequence that is identical to the amino acid sequence of an Fc region found in nature.
  • Native sequence human Fc regions include a native sequence human IgGl Fc region; native sequence human IgG2 Fc region; native sequence human IgG3 Fc region; and native sequence human IgG4 Fc region as well as naturally occurring variants thereof.
  • Native sequence Fc include the various allotypes of Fes (see, e.g. , Jefferis et al. (2009) mAbs 1:1).
  • a “hinge”, “hinge domain” or V’hinge region” or “antibody hinge region” refers to the domain of a heavy chain constant region that joins the CHI domain to the CH2 domain and includes the upper, middle, and lower portions of the hinge (Roux et al. J. Immunol. 1998 161 :4083).
  • the hinge provides varying levels of flexibility between the binding and effector regions of an antibody and also provides sites for intermolecular disulfide bonding between the two heavy chain constant regions.
  • a hinge starts at Glu216 and ends at Gly237 for all IgG isotypes (Roux et al., 1998 J Immunol 161:4083).
  • hinge includes wildtype hinges as well as variants thereof (e.g, non- naturally-occurring hinges or modified hinges).
  • IgG2 hinge includes wildtype IgG2 hinge and variants having 1, 2, 3, 4, 5, 1-3, 1-5, 3-5 and/or at most 5, 4, 3, 2, or 1 mutations, e.g, substitutions, deletions or additions.
  • Exemplary IgG2 hinge variants include IgG2 hinges in which 1, 2, 3 or all 4 cysteines (C219, C220, C226 and C229) are changed to another amino acid.
  • an IgG2 comprises a C219S substitution.
  • a hinge is a hybrid hinge that comprises sequences from at least two isotypes.
  • a hinge may comprise the upper, middle or lower hinge from one isotype and the remainder of the hinge from one or more other isotypes.
  • a hinge can be an IgG2/IgGl hinge, and may comprise, e.g, the upper and middle hinges of IgG2 and the lower hinge of IgGl.
  • a hinge may have effector function or be deprived of effector function.
  • the lower hinge of wildtype IgGl provides effector function.
  • CHI domain refers to the heavy chain constant region linking the variable domain to the hinge in a heavy chain constant domain.
  • a CHI domain starts at Al 18 and ends at V215.
  • the term “CHI domain” includes wildtype CHI domains as well as variants thereof (e.g, non-naturally-occurring CHI domains or modified CHI domains).
  • the term “CHI domain” includes wildtype CHI domains and variants having 1, 2, 3, 4, 5, 1-3, 1-5, 3-5 and/or at most 5, 4, 3, 2, or 1 mutations, e.g, substitutions, deletions or additions.
  • Exemplary CHI domains include CHI domains with mutations that modify a biological activity of an antibody, such as ADCC, CDC or half-life. Modifications to the CHI domain that affect a biological activity of an antibody are provided herein.
  • CH2 domain refers to the heavy chain constant region linking the hinge to the CH3 domain in a heavy chain constant domain. As used herein, a CH2 domain starts at P238 and ends at K340.
  • CH2 domain includes wildtype CH2 domains, as well as variants thereof (e.g, non-naturally-occurring CH2 domains or modified CH2 domains).
  • CH2 domain includes wildtype CH2 domains and variants having 1, 2, 3, 4, 5, 1-3, 1-5, 3-5 and/or at most 5, 4, 3, 2, or 1 mutations, e.g, substitutions, deletions or additions.
  • CH2 domains include CH2 domains with mutations that modify a biological activity of an antibody, such as ADCC, CDC or half-life.
  • a CH2 domain comprises the substitutions A330S/P331S that reduce effector function.
  • Other modifications to the CH2 domain that affect a biological activity of an antibody are provided herein.
  • CH3 domain refers to the heavy chain constant region that is C-terminal to the CH2 domain in a heavy chain constant domain. As used herein, a CH3 domain starts at G341 and ends at K447.
  • the term “CH3 domain” includes wildtype CH3 domains, as well as variants thereof (e.g, non-naturally-occurring CH3 domains or modified CH3 domains).
  • the term “CH3 domain” includes wildtype CH3 domains and variants having 1, 2, 3, 4, 5, 1-3, 1-5, 3-5 and/or at most 5, 4, 3, 2, or 1 mutations, e.g, substitutions, deletions or additions.
  • Exemplary CH3 domains include CH3 domains with mutations that modify a biological activity of an antibody, such as ADCC, CDC or half-life. Modifications to the CH3 domain that affect a biological activity of an antibody are provided herein.
  • the terms “specific binding,” “selective binding,” “selectively binds,” and “specifically binds,” refer to antibody binding to an epitope on a predetermined antigen.
  • the antibody binds with an equilibrium dissociation constant (K D ) of approximately less than 10 7 M, such as approximately less than 10 8 M, 10 9 M or 10 10 M or even lower when determined by, e.g, surface plasmon resonance (SPR) technology in a BIACORE 2000 instrument using the predetermined antigen, as the analyte and the antibody as the ligand, or Scatchard analysis of binding of the antibody to antigen positive cells, and (ii) binds to the predetermined antigen with an affinity that is at least two-fold greater than its affinity for binding to a non-specific antigen (e.g ., BSA, casein) other than the predetermined antigen or a closely-related antigen.
  • K D equilibrium dissociation constant
  • nucleic acid molecules encoding an antibody provided herein.
  • the term “nucleic acid molecule,” as used herein, is intended to include DNA molecules and RNA molecules.
  • a nucleic acid molecule may be single-stranded or double-stranded, and may be cDNA.
  • conservative sequence modifications of the sequences set forth herein, e.g., in Table 1-2, i.e., amino acid sequence modifications which do not abrogate the binding of the antibody encoded by the nucleotide sequence or containing the amino acid sequence, to the antigen.
  • conservative sequence modifications include conservative nucleotide and amino acid substitutions, as well as, nucleotide and amino acid additions and deletions.
  • modifications can be introduced into a sequence by standard techniques known in the art, such as site-directed mutagenesis and PCR-mediated mutagenesis.
  • Conservative amino acid substitutions include ones in which the amino acid residue is replaced with an amino acid residue having a similar side chain.
  • Families of amino acid residues having similar side chains have been defined in the art. These families include amino acids with basic side chains (e.g, lysine, arginine, histidine), acidic side chains (e.g, aspartic acid, glutamic acid), uncharged polar side chains (e.g, glycine, asparagine, glutamine, serine, threonine, tyrosine, cysteine, tryptophan), nonpolar side chains (e.g, alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine), beta- branched side chains (e.g, threonine, valine, isoleucine) and aromatic side chains (e.g, tyrosine, phenylalanine, tryptophan, histidine).
  • basic side chains e.g, lysine, arginine, histidine
  • acidic side chains e.g, aspartic acid, glut
  • a predicted nonessential amino acid residue in an anti-idiotype antibody is preferably replaced with another amino acid residue from the same side chain family.
  • Methods of identifying nucleotide and amino acid conservative substitutions which do not eliminate antigen binding are well-known in the art (see, e.g, Brummell et al., Biochem. 32: 1180-1187 (1993); Kobayashi et al. Protein Eng. 12(10):879-884 (1999); and Burks etal. Proc. Natl. Acad. Sci. USA 94:412-417 (1997)).
  • nucleic acid molecules encoding the heavy and/or light chain variable regions of the antibodies provided herein (e.g, as set forth in Tables 1 and 2).
  • nucleic acid molecules having substantial homology to a sequence provided herein are provided herein.
  • substantially homology indicates that two nucleic acids, or designated sequences thereof, when optimally aligned and compared, are identical, with appropriate nucleotide insertions or deletions, in at least about 80% of the nucleotides, usually at least about 90% to 95%, and more preferably at least about 98% to 99.5% of the nucleotides.
  • substantial homology exists when the segments will hybridize under selective hybridization conditions, to the complement of the strand.
  • antibodies having heavy and/or light chains with substantial homology to a sequence provided herein.
  • substantial homology indicates that two polypeptides, or designated sequences thereof, when optimally aligned and compared, are identical, with appropriate amino acid insertions or deletions, in at least about 80% of the amino acids, usually at least about 90% to 95%, and more preferably at least about 98% to 99.5% of the amino acids.
  • the comparison of sequences and determination of percent identity between two sequences can be accomplished using a mathematical algorithm, as described in the non-limiting examples below.
  • the percent identity between two nucleotide sequences can be determined using the GAP program in the GCG software package (available on the World Wide Web at gcg.com), using a NWSgapdna.CMP matrix and a gap weight of 40, 50, 60, 70, or 80 and a length weight of 1, 2, 3, 4, 5, or 6.
  • the percent identity between two nucleotide or amino acid sequences can also be determined using the algorithm of E. Meyers and W. Miller (CABIOS, 4:11-17 (1989)) which has been incorporated into the ALIGN program (version 2.0), using a PAM120 weight residue table, a gap length penalty of 12 and a gap penalty of 4.
  • the percent identity between two amino acid sequences can be determined using the Needleman and Wunsch (J.
  • vectors encoding the heavy and/or light chain of an antibody provided herein.
  • the term “vector,” as used herein, is intended to refer to a nucleic acid molecule capable of transporting another nucleic acid to which it has been linked.
  • plasmid refers to a circular double stranded DNA loop into which additional DNA segments may be ligated.
  • viral vector Another type of vector is a viral vector, wherein additional DNA segments may be ligated into the viral genome.
  • Certain vectors are capable of autonomous replication in a host cell into which they are introduced (e.g ., bacterial vectors having a bacterial origin of replication and episomal mammalian vectors).
  • vectors e.g., non-episomal mammalian vectors
  • vectors can be integrated into the genome of a host cell upon introduction into the host cell, and thereby are replicated along with the host genome.
  • certain vectors are capable of directing the expression of genes to which they are operatively linked.
  • Such vectors are referred to herein as “recombinant expression vectors” (or simply, “expression vectors”).
  • expression vectors of utility in recombinant DNA techniques are often in the form of plasmids.
  • plasmid and vector may be used interchangeably as the plasmid is the most commonly used form of vector.
  • viral vectors e.g, replication defective retroviruses, adenoviruses and adeno-associated viruses
  • a host cell comprising a nucleic acid molecule disclosed herein.
  • the term “recombinant host cell” (or simply “host cell”), as used herein, is intended to refer to a cell that comprises a nucleic acid that is not naturally present in the cell, and maybe a cell into which a recombinant expression vector has been introduced. It should be understood that such terms are intended to refer not only to the particular subject cell but to the progeny of such a cell. Because certain modifications may occur in succeeding generations due to either mutation or environmental influences, such progeny may not, in fact, be identical to the parent cell, but are still included within the scope of the term “host cell” as used herein.
  • kits for treating or preventing Wu-CoV infection are provided herein.
  • administering refers to the physical introduction of a composition comprising a therapeutic agent to a subject, using any of the various methods and delivery systems known to those skilled in the art.
  • Preferred routes of administration for antibodies described herein include intravenous, intraperitoneal, intramuscular, subcutaneous, spinal or other parenteral routes of administration, for example by injection or infusion.
  • parenteral administration means modes of administration other than enteral and topical administration, usually by injection, and includes, without limitation, intravenous, intraperitoneal, intramuscular, intraarterial, intrathecal, intralymphatic, intralesional, intracap sular, intraorbital, intracardiac, intradermal, transtracheal, subcutaneous, subcuticular, intraarticular, subcapsular, subarachnoid, intraspinal, epidural and intrasternal injection and infusion, as well as in vivo electroporation.
  • an antibody described herein can be administered via a non- parenteral route, such as a topical, epidermal or mucosal route of administration, for example, intranasally, orally, vaginally, rectally, sublingually or topically.
  • Administering can also be performed, for example, once, a plurality of times, and/or over one or more extended periods.
  • the methods provided herein treat Wu-CoV infection in a subject.
  • the terms “treat,” “treating,” and “treatment,” as used herein, refer to any type of intervention or process performed on, or administering an active agent to, the subject with the objective of reversing, alleviating, ameliorating, inhibiting, or slowing down or preventing the progression, development, severity or recurrence of a symptom, complication, condition or biochemical indicia associated with a disease and/or infection.
  • Treatment can be of a subject having a disease or a subject who does not have a disease and/or infection (e.g ., for prophylaxis).
  • the subject being treated is administered an effective dose of an antibody provided herein.
  • effective dose or “effective dosage” is defined as an amount sufficient to achieve or at least partially achieve a desired effect.
  • a “therapeutically effective amount” or “therapeutically effective dosage” of a drug or therapeutic agent is any amount of the drug that, when used alone or in combination with another therapeutic agent, promotes disease regression evidenced by a decrease in severity of disease symptoms, an increase in frequency and duration of disease symptom-free periods, or a prevention of impairment or disability due to the disease affliction.
  • a therapeutically effective amount or dosage of a drug includes a “prophylactically effective amount” or a “prophylactically effective dosage,” which is any amount of the drug that, when administered alone or in combination with another therapeutic agent to a subject at risk of developing a disease and/or infection or of suffering a recurrence of disease and/or infection, inhibits the development or recurrence of the disease and/or infection.
  • a therapeutic agent to promote disease and/or infection regression or inhibit the development or recurrence of the disease and/or infection can be evaluated using a variety of methods known to the skilled practitioner, such as in human subjects during clinical trials, in animal model systems predictive of efficacy in humans, or by assaying the activity of the agent in in vitro assays.
  • the term “subject” includes any human or non-human animal. In certain embodiments provided herein the subject is a human.
  • non-human animal includes all vertebrates, e.g ., mammals and non-mammals, such as non-human primates, sheep, dog, cow, chickens, amphibians, reptiles, etc.
  • Antibody binding affinity to SARS-CoV-2 RBD was determined by ELISA assay. Representative KD values are shown in Table 5, including antibodies that show no binding to SARS-CoV-2 RBD. Results show KD values of between 0.027 and 75.31 pg/ml as determined by ELISA.

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  • Oncology (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Immunology (AREA)
  • Pulmonology (AREA)
  • Communicable Diseases (AREA)
  • Genetics & Genomics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Peptides Or Proteins (AREA)

Abstract

Dans certains aspects, la présente invention concerne des anticorps et des fragments de liaison à l'antigène de ceux-ci spécifiques pour Wu-CoV. Dans certains aspects, la présente invention concerne des méthodes de traitement d'une infection par le Wu-CoV à l'aide des anticorps selon l'invention. Dans certains aspects, l'invention concerne des molécules d'acide nucléique codant pour les anticorps de l'invention, des cellules hôtes comprenant de tels acides nucléiques, et des procédés de fabrication des anticorps selon l'invention utilisant de telles cellules hôtes. Dans certains aspects, l'invention concerne également des compositions pharmaceutiques comprenant lesdits anticorps.
PCT/IB2021/000031 2020-01-24 2021-01-22 Anticorps anti-coronavirus du wuhan WO2021148884A1 (fr)

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* Cited by examiner, † Cited by third party
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US11732030B2 (en) 2020-04-02 2023-08-22 Regeneron Pharmaceuticals, Inc. Anti-SARS-CoV-2-spike glycoprotein antibodies and antigen-binding fragments
US11192940B2 (en) 2020-04-10 2021-12-07 Adagio Therapeutics, Inc. Compounds specific to coronavirus S protein and uses thereof
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US11414479B2 (en) 2020-04-10 2022-08-16 Adagio Therapeutics, Inc. Compounds specific to coronavirus S protein and uses thereof
US11999777B2 (en) 2020-06-03 2024-06-04 Regeneron Pharmaceuticals, Inc. Methods for treating or preventing SARS-CoV-2 infections and COVID-19 with anti-SARS-CoV-2 spike glycoprotein antibodies
WO2024067810A1 (fr) * 2022-09-29 2024-04-04 Nanjing Immunophage Biotech Co., Ltd Anticorps anti-gpr183 et leurs utilisations
WO2024102700A3 (fr) * 2022-11-09 2024-06-20 IgGenix, Inc. Compositions et procédés pour le traitement et la suppression de réactions allergiques

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