# US 11,999,777 B2 · Methods for treating or preventing SARS-CoV-2 infections and COVID-19 with anti-SARS-CoV-2 spike glycoprotein antibodies

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- Number: US 11,999,777 B2
- Document ID: US11999777B2
- Status: Granted
- Kind: B2
- Application number: 17/337,396
- Filed: 2021-06-02
- Published: 2021-12-23
- Granted: 2024-06-04
- Earliest claimed: 2020-06-03
- Assignees: Regeneron Pharmaceuticals, Inc.
- Applicants: Regeneron Pharmaceuticals, Inc.
- Inventors: Samit Ganguly; Jennifer Hamilton; Gary Herman; Andrea Hooper; Flonza Isa; Meagan O'Brien; Sumathi Sivapalasingam; Kenneth Turner; Eduardo Forleo Neto
- Web page: https://patentgrep.com/patent/US11999777B2

## CPC

- A61K 39/215: Coronaviridae, e.g. avian infectious bronchitis virus
- A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)}
- A61K 31/706: containing six-membered rings with nitrogen as a ring hetero atom
- A61K 39/42: viral
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 31/14: for RNA viruses
- C07K 16/104: Severe acute respiratory syndrome coronavirus 2 [SARS‐CoV‐2]
- C07K 16/2866: {against receptors for cytokines, lymphokines, interferons}
- A61K 2039/507: {Comprising a combination of two or more separate antibodies}
- A61K 2039/54: {characterised by the route of administration}
- C07K 2317/30: characterized by aspects of specificity or valency
- C07K 2317/31: multispecific
- C07K 2317/33: Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
- C07K 2317/56: variable (Fv) region, i.e. VH and/or VL
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)

## Abstract

The present invention provides methods for preventing and treating SARS-CoV-2 infections, COVID-19, or symptoms thereof. The methods of the invention feature the administration of one or more antigen-binding molecules (e.g., antibodies) that bind a surface protein of SARS-CoV-2 (e.g., spike protein).

## Claims

### Claim 1

A method for improving one or more clinical parameters of COVID-19, the method comprising administering a therapeutic composition to a subject in need thereof, wherein the therapeutic composition comprises at least one antigen-binding molecule that binds a surface protein of SARS-CoV-2, wherein the at least one antigen-binding molecule is an anti-SARS-CoV-2 spike glycoprotein antibody or antigen-binding fragment thereof comprising three heavy chain complementarity determining regions (HCDRs) and three light chain complementarity determining regions (LCDRs), HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 contained within a heavy chain variable region (HCVR) and light chain variable region (LCVR) amino acid sequence pair comprising the amino acid sequences selected from the group consisting of SEQ ID NOs: 2 and 10, SEQ ID NOs: 22 and 30, and SEQ ID NOs: 42 and 50.

### Claim 2 (depends on 1)

The method of claim 1, wherein the subject is a human patient with laboratory-confirmed SARS-CoV-2 and one or more COVID-19 symptoms.

### Claim 3 (depends on 2)

The method of claim 2, wherein the one or more COVID-19 symptoms comprise fever, cough, or shortness of breath.

### Claim 4 (depends on 2, 3)

The method of claim 2 or claim 3, wherein the subject is selected from the group consisting of: (a) a human COVID-19 patient requiring low-flow oxygen supplementation; (b) a human COVID-19 patient requiring high-intensity oxygen therapy but not on mechanical ventilation; and (c) a human COVID-19 patient requiring mechanical ventilation.

### Claim 5 (depends on 1)

The method of claim 1, wherein the subject is hospitalized due to one or more COVID-19 symptoms.

### Claim 6 (depends on 1)

The method of claim 1, wherein the subject is an outpatient.

### Claim 7

A method for preventing a SARS-CoV-2 infection or COVID-19 in a subject, the method comprising administering a prophylactic composition to the subject, wherein the prophylactic composition comprises at least one antigen-binding molecule that binds a surface protein of SARS-CoV-2, wherein the at least one antigen-binding molecule is an anti-SARS-CoV-2 spike glycoprotein antibody or antigen-binding fragment thereof comprising three heavy chain complementarity determining regions (HCDRs) and three light chain complementarity determining regions (LCDRs), HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, contained within a heavy chain variable region (HCVR) and light chain variable region (LCVR) amino acid sequence pair comprising the amino acid sequences selected from the group consisting of SEQ ID NOs: 2 and 10, SEQ ID NOs: 22 and 30, and SEQ ID NOs: 42 and 50.

### Claim 8 (depends on 7)

The method of claim 7, wherein the subject is an uninfected individual at high risk of SARS-CoV-2 infection.

### Claim 9 (depends on 8)

The method of claim 8, wherein the subject at high risk of SARS-CoV-2 infection is a healthcare worker, a first responder, or a household member of an individual with a positive test for a SARS-CoV-2 infection.

### Claim 10 (depends on 1, 7)

The method of claim 1 or claim 7, wherein the therapeutic or prophylactic composition comprises a first antigen-binding molecule that binds a first epitope on a surface protein of SARS-CoV-2, and a second antigen-binding molecule that binds a second epitope on a surface protein of SARS-CoV-2, wherein the first epitope and the second epitope are structurally non-overlapping.

### Claim 11 (depends on 10)

The method of claim 10, wherein the therapeutic or prophylactic composition further comprises a third antigen-binding molecule that binds a third epitope on a surface protein of SARS-CoV-2, wherein the third epitope is structurally non-overlapping with the first epitope and the second epitope.

### Claim 12 (depends on 1, 7)

The method of claim 1 or claim 7, wherein the therapeutic or prophylactic composition comprises a first antigen-binding molecule that binds a first epitope on a surface protein of SARS-CoV-2, and a second antigen-binding molecule that binds a second epitope on a surface protein of SARS-CoV-2, wherein the first antigen-binding molecule and the second antigen-binding molecule are capable of simultaneously binding the surface protein of SARS-CoV-2.

### Claim 13 (depends on 12)

The method of claim 12, wherein the first antigen-binding molecule is a first anti-SARS-CoV-2 spike glycoprotein antibody or antigen-binding fragment thereof comprising six complementarity determining regions, HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, contained within a heavy chain variable region (HCVR) and light chain variable region (LCVR) amino acid sequence pair comprising the amino acid sequences of SEQ ID NOs: 2 and 10, and the second antigen-binding molecule is a second anti-SARS-CoV-2 spike glycoprotein antibody or antigen-binding fragment thereof comprising six complementarity determining regions, HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, contained within a heavy chain variable region (HCVR) and light chain variable region (LCVR) amino acid sequence pair comprising the amino acid sequences of SEQ ID NOs: 22 and 30.

### Claim 14 (depends on 12)

The method of claim 12, wherein the therapeutic or prophylactic composition further comprises a third antigen-binding molecule that binds a third epitope on a surface protein of SARS-CoV-2, wherein the first antigen-binding molecule, the second antigen-binding molecule, and the third antigen-binding molecule are capable of simultaneously binding the surface protein of SARS-CoV-2.

### Claim 15 (depends on 10)

The method of claim 10, wherein:
a) the first antigen-binding molecule comprises three heavy chain complementarity determining regions (CDRs) (HCDR1, HCDR2 and HCDR3) contained within a heavy chain variable region (HCVR) comprising the amino acid sequence set forth in SEQ ID NO: 2, and three light chain complementarity determining regions (CDRs) (LCDR1, LCDR2 and LCDR3) contained within a light chain variable region (LCVR) comprising the amino acid sequence set forth in SEQ ID NO: 10; and
b) the second antigen-binding molecule comprises three heavy chain complementarity determining regions (CDRs) (HCDR1, HCDR2 and HCDR3) contained within a heavy chain variable region (HCVR) comprising the amino acid sequence set forth in SEQ ID NO: 22, and three light chain complementarity determining regions (CDRs) (LCDR1, LCDR2 and LCDR3) contained within a light chain variable region (LCVR) comprising the amino acid sequence set forth in SEQ ID NO: 30.

### Claim 16 (depends on 10)

The method of claim 10, wherein the surface protein of SARS-CoV-2 is a spike (S) protein comprising a receptor binding domain comprising an amino acid sequence at least 80% identical to SEQ ID NO: 59.

### Claim 17 (depends on 1, 7)

The method of claim 1 or claim 7, wherein the heavy chain CDRs and the light chain CDRs, HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, comprise the amino acid sequences, respectively, selected from the group consisting of SEQ ID NOs: 4, 6, 8, 12, 14, and 16; 24, 26, 28, 32, 34, and 26; and 44, 46, 48, 52, 34, and 54.

### Claim 18 (depends on 17)

The method of claim 17, wherein the anti-SARS-CoV-2 spike glycoprotein antibody or antigen-binding fragment comprises a HCVR/LCVR amino acid sequence pair comprising the amino acid sequences selected from the group consisting of SEQ ID NOs: 2 and 10, SEQ ID NOs: 22 and 30, and SEQ ID NOs: 42 and 50.

### Claim 19 (depends on 1, 7)

The method of claim 1 or claim 7, wherein the anti-SARS-CoV-2 spike glycoprotein antibody comprises a human IgG heavy chain constant region.

### Claim 20 (depends on 19)

The method of claim 19, wherein the anti-SARS-CoV-2 spike glycoprotein antibody comprises a heavy chain constant region of IgG1 or IgG4 isotype.

### Claim 21 (depends on 19)

The method of claim 19, wherein the anti-SARS-CoV-2 spike glycoprotein antibody comprises a heavy chain and light chain amino acid sequence pair selected from the group consisting of SEQ ID NOs: 18 and 20, SEQ ID NOs: 38 and 40, and SEQ ID NOs: 56 and 58.

### Claim 22 (depends on 10)

The method of claim 10, wherein the first antigen-binding molecule is a first anti-SARS-CoV-2 spike glycoprotein antibody or antigen-binding fragment thereof comprising six complementarity determining regions, HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, contained within a heavy chain variable region (HCVR) and light chain variable region (LCVR) amino acid sequence pair comprising the amino acid sequences of SEQ ID NOs: 2 and 10, and the second antigen-binding molecule is a second anti-SARS-CoV-2 spike glycoprotein antibody or antigen-binding fragment thereof comprising six complementarity determining regions, HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, contained within a heavy chain variable region (HCVR) and light chain variable region (LCVR) amino acid sequence pair comprising the amino acid sequences of SEQ ID NOs: 22 and 30.

### Claim 23 (depends on 22)

The method of claim 22, wherein the first anti-SARS-CoV-2 spike glycoprotein antibody or antigen-binding fragment comprises six complementarity determining regions, HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, comprising the amino acid sequences, respectively, of SEQ ID NOs: 4, 6, 8, 12, 14, and 16, and the second anti-SARS-CoV-2 spike glycoprotein antibody or antigen-binding fragment comprises six complementarity determining regions, HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, comprising the amino acid sequences, respectively, of SEQ ID NOs: 24, 26, 28, 32, 34, and 36.

### Claim 24 (depends on 23)

The method of claim 23, wherein the first anti-SARS-CoV-2 spike glycoprotein antibody or antigen-binding fragment comprises a HCVR and LCVR amino acid sequence pair comprising the amino acid sequences of SEQ ID NOs: 2 and 10N/10n, and the second anti-SARS-CoV-2 spike glycoprotein antibody or antigen-binding fragment comprises a HCVR and LCVR amino acid sequence pair comprising the amino acid sequences of SEQ ID NOs: 22 and 30.

### Claim 25 (depends on 22)

The method of claim 22, wherein the first and the second anti-SARS-CoV-2 spike glycoprotein antibodies comprises human IgG heavy chain constant regions.

### Claim 26 (depends on 25)

The method of claim 25, wherein the first and the second anti-SARS-CoV-2 spike glycoprotein antibodies comprises heavy chain constant regions of IgG1 or IgG4 isotype.

### Claim 27 (depends on 25)

The method of claim 25, wherein the first anti-SARS-CoV-2 spike glycoprotein antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 18 and a light chain comprising the amino acid sequence of SEQ ID NO: 20, and the second anti-SARS-CoV-2 spike glycoprotein antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 38 and a light chain comprising the amino acid sequence of SEQ ID NO: 40.

### Claim 28 (depends on 1, 7)

The method of claim 1 or claim 7, wherein the antigen-binding molecule is an anti-SARS-CoV-2 spike glycoprotein antibody or antigen-binding fragment thereof comprising six complementarity determining regions, HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, contained within a heavy chain variable region (HCVR) comprising the amino acid sequence of SEQ ID NO: 42 and light chain variable region (LCVR) comprising the amino acid sequence of SEQ ID NO: 50.

### Claim 29 (depends on 28)

The method of claim 28, wherein the anti-SARS-CoV-2 spike glycoprotein antibody or antigen-binding fragment comprises six complementarity determining regions, HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, comprising the amino acid sequences, respectively, of SEQ ID NOs: 44, 46, 48, 52, 34, and 54.

### Claim 30 (depends on 29)

The method of claim 29, wherein the anti-SARS-CoV-2 spike glycoprotein antibody or antigen-binding fragment comprises a HCVR comprising the amino acid sequence of SEQ ID NO: 42, and a LCVR comprising the amino acid sequence of SEQ ID NOs: 50.

### Claim 31 (depends on 28)

The method of claim 28, wherein the anti-SARS-CoV-2 spike glycoprotein antibody comprises a human IgG heavy chain constant region.

### Claim 32 (depends on 31)

The method of claim 31, wherein the anti-SARS-CoV-2 spike glycoprotein antibody comprises a heavy chain constant region of IgG1 or IgG4 isotype.

### Claim 33 (depends on 31)

The method of claim 31, wherein the anti-SARS-CoV-2 spike glycoprotein antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 56, and a light chain comprising the amino acid sequence of SEQ ID NO: 58.

### Claim 34 (depends on 1, 7)

The method of claim 1 or claim 7, wherein the therapeutic composition comprises 1 mg to 10 g of the antigen-binding molecule(s).

### Claim 35 (depends on 1, 7)

The method of claim 1 or claim 7, wherein the therapeutic composition comprises about 1.2 g of mAb10933 and about 1.2 g of mAb10987.

### Claim 36 (depends on 1, 7)

The method of claim 1 or claim 7, wherein the therapeutic composition comprises about 150 mg of mAb10933 and about 150 mg of mAb10987.

### Claim 37 (depends on 1, 7)

The method of claim 1 or claim 7, wherein the therapeutic composition comprises about 300 mg of mAb10933 and about 300 mg of mAb10987.

### Claim 38 (depends on 1, 7)

The method of claim 1 or claim 7, wherein the therapeutic composition comprises about 600 mg of mAb10933 and about 600 mg of mAb10987.

### Claim 39 (depends on 1, 7)

The method of claim 1 or claim 7, wherein the therapeutic composition comprises from 150 mg to 1200 mg of mAb10933 and from 150 mg to 1200 mg of mAb10987.

### Claim 40 (depends on 1, 7)

The method of claim 1 or claim 7, wherein the therapeutic or prophylactic composition is administered to the subject by intravenous infusion or subcutaneous injection.

### Claim 41 (depends on 1)

The method of claim 1, wherein, following administration of the therapeutic composition, the subject exhibits one or more efficacy parameters selected from the group consisting of:
(a) reduction from baseline in SARS-CoV-2 viral shedding;
(b) at least 1 point improvement in clinical status using a 7-point ordinal scale;
(c) reduction or elimination of need for oxygen supplementation;
(d) reduction or elimination of need for mechanical ventilation;
(e) prevention of COVID-19-related mortality;
(f) prevention of all-cause mortality; and
(g) change in serum concentration of one or more disease-related biomarkers.

### Claim 42 (depends on 41)

The method of claim 41, wherein the 7-point ordinal scale is:
[1] Death;
[2] Hospitalized, requiring invasive mechanical ventilation or extracorporeal membrane oxygenation;
[3] Hospitalized, requiring non-invasive ventilation or high flow oxygen devices;
[4] Hospitalized, requiring supplemental oxygen;
[5] Hospitalized, not requiring supplemental oxygen—requiring ongoing medical care (COVID-19-related or otherwise);
[6] Hospitalized, not requiring supplemental oxygen—no longer requires ongoing medical care; and
[7] Not hospitalized.

### Claim 43 (depends on 41, 42)

The method of claim 41 or 42, wherein the one or more efficacy parameters are measured 21 days after administration of a first dose of the therapeutic composition.

### Claim 44 (depends on 41)

The method of claim 41, wherein the reduction from baseline in SARS-CoV-2 viral shedding is determined by real-time quantitative PCR (RT-qPCR) in nasopharyngeal swab samples, nasal samples, or saliva samples.

### Claim 45 (depends on 41)

The method of claim 41, wherein the change in serum concentration of one or more disease-related biomarkers is a change in c-reactive protein, lactate dehydrogenase, D-dimer, or ferritin.

### Claim 46 (depends on 1)

The method of claim 1, further comprising administering an additional therapeutic agent to the subject.

### Claim 47 (depends on 46)

The method of claim 46, wherein the additional therapeutic agent is an antiviral compound.

### Claim 48 (depends on 47)

The method of claim 47, wherein the antiviral compound is remdesivir.

### Claim 49 (depends on 46)

The method of claim 46, wherein the additional therapeutic agent is an IL-6 or IL-6R blocker.

### Claim 50 (depends on 49)

The method of claim 49, wherein the additional therapeutic agent is tocilizumab or sarilumab.

### Claim 51 (depends on 46)

The method of claim 46, wherein the additional therapeutic agent is a steroid.

### Claim 52 (depends on 1, 7)

The method of claim 1 or claim 7, wherein the subject is seronegative for SARS-CoV-2 infection.

### Claim 53

A method for improving one or more clinical parameters of a SARS-CoV-2 infection, the method comprising administering a therapeutic composition to a subject with a SARS-CoV-2 infection, wherein the therapeutic composition comprises a first anti-SARS-CoV-2 spike glycoprotein antibody or antigen-binding fragment thereof comprising three heavy chain complementarity determining regions (HCDRs) and three light chain complementarity determining regions (LCDRs) contained within a heavy chain variable region (HCVR) and light chain variable region (LCVR) amino acid sequence pair comprising the amino acid sequences of SEQ ID NOs: 2 and 10N/10n, and a second anti-SARS-CoV-2 spike glycoprotein antibody or antigen-binding fragment thereof comprising three HCDRs and three LCDRs contained within an HCVR and an LCVR amino acid sequence pair comprising the amino acid sequences of SEQ ID NOs: 22 and 30, wherein a time to alleviate at least one clinical parameter of a SARS-CoV-2 infection in a population of seronegative subjects administered said therapeutic composition is shorter than that of a comparable population of seronegative subjects administered a placebo.

### Claim 54

A method for improving one or more clinical parameters of a SARS-CoV-2 infection, the method comprising administering a therapeutic composition to a subject with a SARS-CoV-2 infection, wherein the therapeutic composition comprises a first anti-SARS-CoV-2 spike glycoprotein antibody or antigen-binding fragment thereof comprising three heavy chain complementarity determining regions (HCDRs) and three light chain complementarity determining regions (LCDRs) contained within a heavy chain variable region (HCVR) and light chain variable region (LCVR) amino acid sequence pair comprising the amino acid sequences of SEQ ID NOs: 2 and 10, and a second anti-SARS-CoV-2 spike glycoprotein antibody or antigen-binding fragment thereof comprising three HCDRs and three LCDRs contained within an HCVR and an LCVR amino acid sequence pair comprising the amino acid sequences of SEQ ID NOs: 22 and 30, wherein a time to alleviate at least one clinical parameter of a SARS-CoV-2 infection in a population of seronegative subjects administered said therapeutic composition is shorter than that of a comparable population of seropositive subjects.

### Claim 55

A method for improving one or more clinical parameters of a SARS-CoV-2 infection, the method comprising administering a therapeutic composition to a subject with a SARS-CoV-2 infection, wherein the therapeutic composition comprises a first anti-SARS-CoV-2 spike glycoprotein antibody or antigen-binding fragment thereof comprising three heavy chain complementarity determining regions (HCDRs) and three light chain complementarity determining regions (LCDRs) contained within a heavy chain variable region (HCVR) and light chain variable region (LCVR) amino acid sequence pair comprising the amino acid sequences of SEQ ID NOs: 2 and 10, and a second anti-SARS-CoV-2 spike glycoprotein antibody or antigen-binding fragment thereof comprising three HCDRs and three LCDRs contained within an HCVR and an LCVR amino acid sequence pair comprising the amino acid sequences of SEQ ID NOs: 22 and 30, wherein said therapeutic composition reduces viral load through 7 days post-administration (Day 7) in a population of subjects as compared to the day of administration (Day 0).

### Claim 56 (depends on 55)

The method of claim 55, wherein the time-weighted-average reduction from baseline nasopharyngeal (NP) viral load through Day 7 in a seronegative population of subjects is at least 0.86 log 10 copies/mL more in patients treated with 0.6 g of the first anti-SARS-CoV-2 spike glycoprotein antibody and 0.6 g of the second anti-SARS-CoV-2 spike glycoprotein antibody, as compared to a comparable population of subjects treated with a placebo, wherein the p value is <0.0001.

### Claim 57 (depends on 55)

The method of claim 55, wherein the reduction from baseline nasopharyngeal (NP) viral load through Day 7 in a seronegative population of subjects is at least 1.04 log 10 copies/mL more in patients treated with 1.2 g of the first anti-SARS-CoV-2 spike glycoprotein antibody and 1.2 g of the second anti-SARS-CoV-2 spike glycoprotein antibody, as compared to a comparable population of subjects treated with a placebo, wherein the p value is <0.0001.

### Claim 58 (depends on 55)

The method of claim 55, wherein the average reduction from baseline nasopharyngeal (NP) viral load through Day 7 in the population of subjects is at least 0.71 log 10 copies/mL more in patients treated with 0.6 g of the first anti-SARS-CoV-2 spike glycoprotein antibody and 0.6 g of the second anti-SARS-CoV-2 spike glycoprotein antibody, as compared to a comparable population of subjects treated with a placebo, wherein the p value is <0.0001.

### Claim 59 (depends on 55)

The method of claim 55, wherein the average reduction from baseline nasopharyngeal (NP) viral load through Day 7 in the population of subjects is a 0.86 log 10 copies/mL more in patients treated with 1.2 g of the first anti-SARS-CoV-2 spike glycoprotein antibody and 1.2 g of the second anti-SARS-CoV-2 spike glycoprotein antibody, as compared to a comparable population of subjects treated with a placebo, wherein the p value is <0.0001.

### Claim 60

A method for improving one or more clinical parameters of a SARS-CoV-2 infection, the method comprising administering a therapeutic composition to a subject with a SARS-CoV-2 infection, wherein the therapeutic composition comprises a first anti-SARS-CoV-2 spike glycoprotein antibody or antigen-binding fragment thereof comprising three heavy chain complementarity determining regions (HCDRs) and three light chain complementarity determining regions (LCDRs) contained within a heavy chain variable region (HCVR) and light chain variable region (LCVR) amino acid sequence pair comprising the amino acid sequences of SEQ ID NOs: 2 and 10, and a second anti-SARS-CoV-2 spike glycoprotein antibody or antigen-binding fragment thereof comprising three HCDRs and three LCDRs contained within an HCVR and an LCVR amino acid sequence pair comprising the amino acid sequences of SEQ ID NOs: 22 and 30, wherein said therapeutic composition reduces viral load in a population of subjects.

### Claim 61 (depends on 60)

The method of claim 60, wherein administration of said therapeutic composition comprises administering 0.6 g of the first anti-SARS-CoV-2 spike glycoprotein antibody and 0.6 g of the second anti-SARS-CoV-2 spike glycoprotein antibody, and wherein said administering produces a mean reduction in viral load at day 7 post-administration compared to baseline viral load measured at day 0 pre-administration of at least 3.00 log 10 copies/mL.

### Claim 62 (depends on 61)

The method of claim 61, wherein said reduction is at least 3.50 log 10 copies/mL.

### Claim 63 (depends on 61)

The method of claim 61, wherein said reduction is at least 3.90 log 10 copies/mL.

### Claim 64 (depends on 60)

The method of claim 60, wherein administration of said therapeutic composition comprises administering 1.2 g of the first anti-SARS-CoV-2 spike glycoprotein antibody and 1.2 g of the second anti-SARS-CoV-2 spike glycoprotein antibody, and wherein said administering produces a mean reduction in viral load at day 7 post-administration compared to baseline viral load measured at day 0 pre-administration of at least 3.50 log 10 copies/mL.

### Claim 65 (depends on 61)

The method of claim 61, wherein said reduction is at least 3.75 log 10 copies/mL.

### Claim 66 (depends on 61)

The method of claim 61, wherein said reduction is at least 4.09 log 10 copies/mL.

### Claim 67

A method for improving one or more clinical parameters of a SARS-CoV-2 infection, the method comprising administering a therapeutic composition to a subject with a SARS-CoV-2 infection, wherein the therapeutic composition comprises a first anti-SARS-CoV-2 spike glycoprotein antibody or antigen-binding fragment thereof comprising three heavy chain complementarity determining regions (HCDRs) and three light chain complementarity determining regions (LCDRs) contained within a heavy chain variable region (HCVR) and light chain variable region (LCVR) amino acid sequence pair comprising the amino acid sequences of SEQ ID NOs: 2 and 10, and a second anti-SARS-CoV-2 spike glycoprotein antibody or antigen-binding fragment thereof comprising three HCDRs and three LCDRs contained within an HCVR and an LCVR amino acid sequence pair comprising the amino acid sequences of SEQ ID NOs: 22 and 30, wherein said therapeutic composition reduces time to symptom alleviation by a median of 4 days in a population of subjects treated with 0.6 g of the first anti-SARS-CoV-2 spike glycoprotein antibody and 0.6 g of the second anti-SARS-CoV-2 spike glycoprotein antibody or 1.2 g of the first anti-SARS-CoV-2 spike glycoprotein antibody and 1.2 g of the second anti-SARS-CoV-2 spike glycoprotein antibody, as compared to a comparable population of subjects treated with a placebo.

### Claim 68 (depends on 60, 67)

The method of claim 60 or claim 67, wherein said subjects and/or population of subjects comprises subjects not hospitalized for COVID-19.