Antigen-binding molecules that target SARS-CoV-2

Abstract

The present invention, in various embodiments, provides polypeptides (e.g., camelid antibodies and antigen-binding fragments thereof) that specifically bind to the spike glycoprotein of a severe acute respiratory syndrome coronavirus (e.g., SARS-CoV-2-spike). The present invention, in various embodiments, also provides fusion proteins comprising one or more of the polypeptides, polynucleotides encoding the polypeptides, vectors and host cells suitable for expressing the polypeptides, and methods for treating viral infections (e.g., COVID-19).

Claims

[Claim 1] Immunoglobulin heavy chain variable domain (V Ｈ An antibody against severe acute respiratory syndrome coronavirus 2 spike glycoprotein (SARS-CoV-2-spike) or an antigen-binding fragment thereof, comprising the V Ｈ An anti-SARS-CoV-2-spike antibody or its antigen-binding fragment, comprising heavy chain complementarity-determining region 1 (HCDR1), heavy chain complementarity-determining region 2 (HCDR2), and heavy chain complementarity-determining region 3 (HCDR3), the heavy chain complementarity-determining region 1 (HCDR1), heavy chain complementarity-determining region 2 (HCDR2), and heavy chain complementarity-determining region 3 (HCDR3), which are identical to the amino acid sequences of SEQ ID NO: 4, respectively. [Claim 2] a) The above V Ｈ is at least 85% identical to the amino acid sequence of Sequence ID No. 4, b) The above V Ｈ This includes 1 to 10 amino acid substitutions relative to the amino acid sequence of SEQ ID NO: 4, or a) and b) both are true. The anti-SARS-CoV-2-spike antibody or its antigen-binding fragment according to claim 1. [Claim 3] a) The above V Ｈ Does this include the human framework domain? b) The anti-SARS-CoV-2-spike antibody is a single-domain antibody, c) The anti-SARS-CoV-2-spike antibody or its antigen-binding fragment further comprises an antibody heavy chain constant domain sequence, or Any of the above combinations The anti-SARS-CoV-2-spike antibody or antigen-binding fragment thereof according to claim 1 or 2. [Claim 4] The aforementioned V Ｈ The anti-SARS-CoV-2-spike antibody or antigen-binding fragment thereof according to any one of claims 1 to 3, comprising the amino acid sequence of SEQ ID NO:

4. [Claim 5] The anti-SARS-CoV-2-spike antibody or antigen-binding fragment thereof according to claim 3c) or 4, wherein the antibody heavy chain constant domain is an IgG1 heavy chain constant domain. [Claim 6] An anti-SARS-CoV-2-spike antibody or antigen-binding fragment thereof according to any one of claims 1 to 5, comprising the amino acid sequence of SEQ ID NO:

15. [Claim 7] The anti-SARS-CoV-2 spike antibody or its antigen-binding fragment binds to a variant of SARS-CoV-2 having a SARS-CoV-2 spike containing D614G. An anti-SARS-CoV-2-spike antibody or its antigen-binding fragment according to any one of claims 1 to 6. [Claim 8] A fusion protein comprising an anti-SARS-CoV-2-spike antibody or an antigen-binding fragment thereof, as described in any one of claims 1 to 7. [Claim 9] A polynucleotide comprising a sequence encoding an anti-SARS-CoV-2-spike antibody or an antigen-binding fragment thereof, as described in any one of claims 1 to 7. [Claim 10] A host cell containing the polynucleotide described in claim 9. [Claim 11] A composition comprising an anti-SARS-CoV-2-spike antibody or an antigen-binding fragment thereof according to any one of claims 1 to 7, and one or more pharmaceutical excipients, diluents, or carriers. [Claim 12] The composition according to claim 11 for use in a method of treating a disease caused by SARS-CoV-2 in a person in need thereof. [Claim 13] A composition according to claim 11 for use in a method for inhibiting fusion between SARS-CoV-2-spike and cells in a subject, wherein the method comprises contacting the cells with an effective amount of the composition according to claim 11. [Claim 14] The aforementioned subject is, a) Having COVID-19, b) Is there a risk of developing COVID-19? c) Are they human? d) Do you have heart disease? e) Do you have diabetes? f) Do you have a lung disease? g) Are you a smoker? h) Is your immune system weakened? i) Are you receiving immunosuppressive therapy? j) Whether you are 40 years of age or older, Any of the above combinations A composition for use according to claim 12 or 13. [Claim 15] a) The aforementioned heart disease is congestive heart disease, coronary artery disease, hypertensive heart disease, inflammatory heart disease, pulmonary heart disease, rheumatic heart disease, heart valve disease, cardiomyopathy, heart failure, or any combination of the above. b) The lung disease is acute respiratory distress syndrome, asthma, bronchitis, COPD, emphysema, lung tumor, pleural cavity disease, pulmonary vascular disease, respiratory tract infection, or any combination of the above. or both a) and b), The composition for use according to claim 14. [Claim 16] a) Is the heart failure congestive heart failure? b) The inflammatory heart disease is endocarditis, cardiac hypertrophy, myocarditis, or any combination of the above. c) The respiratory tract infection is an upper respiratory tract infection, a lower respiratory tract infection, or pneumonia, d) The pleural cavity disease is either pleural mesothelioma or tension pneumothorax, e) The pulmonary vascular disease is embolism, edema, arterial hypertension, or hemorrhage, or Any of the above combinations The composition for use according to claim 15. [Claim 17] A composition for use according to any one of claims 12 to 16, characterized in that it is administered to the subject in combination with a further therapeutic agent. [Claim 18] The composition for use according to claim 17, wherein the further therapeutic agent comprises an antiviral agent, an ACE2 inhibitor, a further SARS-CoV-2 spike-binding antibody, an antibiotic, an antimalarial agent, a vaccine, or any combination thereof. [Claim 19] a) The further SARS-CoV-2 spike-binding antibody includes bamranivimab, etesevimab, casilibimab, imdevimab, or any combination thereof. b) The antiviral agent includes oseltamivir (tamiflu), favipiravir, amantadine, remdesivir, rimantadine, preconalil, antisense RNA against SARS-CoV-2, siRNA against SARS-CoV-2, or any combination thereof. c) The ACE2 inhibitor comprises RNAi against ACE2, siRNA against ACE2, a CRISPR-based inhibitor of ACE2, soluble ACE2, soluble ACE2 variants, an anti-ACE2 antibody, or any combination thereof. d) The antibiotic contains azithromycin, e) The antimalarial agent contains chloroquine or f) The vaccine is either a nucleic acid vaccine or an inactivated virus vaccine, or Any of the above combinations The composition for use according to claim 18. [Claim 20] The composition for use according to claim 19, wherein the vaccine comprises mRNA-1273, BNT162, INO-4800, AZD1222, Ad5-nCoV, PiCoVacc, NVX-CoV2373, or any combination thereof.

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