JPWO2021247779A5

JPWO2021247779A5 -

Info

Publication number: JPWO2021247779A5
Application number: JP2022574373A
Authority: JP
Publication date: 2024-06-10

Claims

A therapeutic pharmaceutical composition comprising at least one antigen-binding molecule that binds to a surface protein of SARS-CoV-2 for improving one or more clinical parameters of COVID-19 in a subject in need of such improvement.

2. The pharmaceutical composition of claim 1, wherein: (a) the subject is a human patient with laboratory-confirmed SARS-CoV-2 and one or more symptoms of COVID-19, optionally wherein the one or more symptoms of COVID-19 include fever, cough, or shortness of breath, and/or the subject is selected from the group consisting of: a human COVID-19 patient requiring low-flow supplemental oxygen; a human COVID-19 patient requiring high-load oxygen therapy but not receiving mechanical ventilation; and a human COVID-19 patient requiring mechanical ventilation; and/or (b) the subject is hospitalized due to one or more symptoms of COVID-19 or the subject is an outpatient.

A prophylactic pharmaceutical composition comprising at least one antigen binding molecule that binds to a surface protein of SARS-CoV-2 for preventing SARS-CoV-2 infection or COVID-19 in a subject, optionally wherein the subject is an uninfected individual at high risk for SARS-CoV-2 infection, and further optionally wherein the subject at high risk for SARS-CoV-2 infection is a healthcare worker, first responder, or a family member of an individual who has tested positive for SARS-CoV-2 infection.

(a) the therapeutic or prophylactic pharmaceutical composition comprises a first antigen binding molecule that binds to a first epitope on a surface protein of SARS-CoV-2 and a second antigen binding molecule that binds to a second epitope on a surface protein of SARS-CoV-2, wherein the first epitope and the second epitope do not structurally overlap, and optionally the therapeutic or prophylactic composition further comprises a third antigen binding molecule that binds to a third epitope on a surface protein of SARS-CoV-2, wherein the third epitope does not structurally overlap with the first epitope and the second epitope; or
(b) the therapeutic or prophylactic composition comprises a first antigen binding molecule that binds to a first epitope on a surface protein of SARS-CoV-2 and a second antigen binding molecule that binds to 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 to the surface protein of SARS-CoV-2, and optionally the therapeutic or prophylactic composition further comprises a third antigen binding molecule that binds to 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 to the surface protein of SARS-CoV-2;
In some cases,
i) 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;
ii) 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;
iii) The therapeutic or prophylactic pharmaceutical composition according to any one of claims 1 to 3, wherein the third 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: 73, 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: 81.

The therapeutic or prophylactic pharmaceutical composition according to any one of claims 1 to 4, wherein the surface protein of SARS-CoV-2 is a spike (S) protein that includes a receptor-binding domain that includes an amino acid sequence that is at least 80% identical to SEQ ID NO:59.

(a) the 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-LCDR3, contained within a heavy chain variable region (HCVR) and light chain variable region (LCVR) amino acid sequence pair comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 2/10, 22/30, 42/50, and 73/81, and optionally (i) the anti-SARS-CoV-2 spike glycoprotein antibody comprises a human IgG heavy chain constant region;
(ii) the anti-SARS-CoV-2 spike glycoprotein antibody comprises a human IgG heavy chain constant region of the IgG1 or IgG4 isotype; or (iii) the anti-SARS-CoV-2 spike glycoprotein antibody comprises a heavy and light chain amino acid sequence pair selected from the group consisting of SEQ ID NOs: 18/20, 38/40, 56/58, and 89/91; or
(b) the antigen-binding molecule is an anti-SARS-CoV-2 spike glycoprotein antibody or antigen-binding fragment thereof comprising HCDR1-HCDR2-HCDR3-LCDR1-LCDR2-LCDR3, each of which comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 4-6-8-12-14-16, 24-26-28-32-34-36, 44-46-48-52-34-54, and 75-77-79-83-85-87, and optionally (i) the anti-SARS-CoV-2 spike glycoprotein antibody comprises a human IgG heavy chain constant region;
(ii) the anti-SARS-CoV-2 spike glycoprotein antibody is IgG1 or
(iii) the anti-SARS-CoV-2 spike glycoprotein antibody comprises a heavy and light chain amino acid sequence pair selected from the group consisting of SEQ ID NOs: 18/20, 38/40, 56/58, and 89/91; or
(c) the antigen-binding molecule is an anti-SARS-CoV-2 spike glycoprotein antibody or antigen-binding fragment thereof, comprising an HCVR/LCVR amino acid sequence pair comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 2/10, 22/30, 42/50, and 73/81, and optionally (i) the anti-SARS-CoV-2 spike glycoprotein antibody comprises a human IgG heavy chain constant region;
(ii) the anti-SARS-CoV-2 spike glycoprotein antibody comprises a human IgG heavy chain constant region of the IgG1 or IgG4 isotype; or (iii) the anti-SARS-CoV-2 spike glycoprotein antibody comprises a heavy and light chain amino acid sequence pair selected from the group consisting of SEQ ID NOs: 18/20, 38/40, 56/58, and 89/91; or (d) the antigen binding molecule is an anti-SARS-CoV-2 spike glycoprotein antibody with the same binding and/or blocking properties as a reference antibody comprising a HCVR/LCVR amino acid sequence pair comprising amino acid sequences selected from the group consisting of SEQ ID NOs: 2/10, 22/30, 42/50, and 73/81; or (e) The therapeutic or prophylactic pharmaceutical composition of any one of claims 1 to 5, wherein the antigen-binding molecule is an anti-SARS-CoV-2 spike glycoprotein antibody having the same binding and/or blocking properties as a reference antibody comprising a heavy and light chain amino acid sequence pair selected from the group consisting of SEQ ID NOs: 18/20, 38/40, 56/58, and 89/91.

(a) the first antigen-binding molecule is a first anti-SARS-CoV-2 spike glycoprotein antibody or an antigen-binding fragment thereof, comprising six complementarity determining regions, HCDR1-HCDR2-HCDR3-LCDR1-LCDR2-LCDR3, contained within a heavy chain variable region (HCVR) and light chain variable region (LCVR) amino acid sequence pair comprising the amino acid sequence of SEQ ID NO:2/10; and the second antigen-binding molecule is a second anti-SARS-CoV-2 spike glycoprotein antibody or an antigen-binding fragment thereof, comprising six complementarity determining regions, HCDR1-HCDR2-HCDR3-LCDR1-LCDR2-LCDR3, contained within a heavy chain variable region (HCVR) and light chain variable region (LCVR) amino acid sequence pair comprising the amino acid sequence of SEQ ID NO:22/30;
Optionally, said first and said second anti-SARS-CoV-2 spike glycoprotein antibodies comprise a human IgG heavy chain constant region; said first and said second anti-SARS-CoV-2 spike glycoprotein antibodies comprise a human IgG heavy chain constant region of an IgG1 or IgG4 isotype; or said 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 said 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;
(b) the first antigen-binding molecule is a first anti-SARS-CoV-2 spike glycoprotein antibody or antigen-binding fragment thereof, the first anti-SARS-CoV-2 spike glycoprotein antibody or antigen-binding fragment thereof comprising six complementarity determining regions, HCDR1-HCDR2-HCDR3-LCDR1-LCDR2-LCDR3, each comprising the amino acid sequences of SEQ ID NOs: 4-6-8-12-14-16; and the second antigen-binding molecule is a second anti-SARS-CoV-2 spike glycoprotein antibody or antigen-binding fragment thereof, the second anti-SARS-CoV-2 spike glycoprotein antibody or antigen-binding fragment thereof comprising six complementarity determining regions, HCDR1-HCDR2-HCDR3-LCDR1-LCDR2-LCDR3, each comprising the amino acid sequences of SEQ ID NOs: 24-26-28-32-34-36;
Optionally, said first and said second anti-SARS-CoV-2 spike glycoprotein antibodies comprise a human IgG heavy chain constant region; said first and said second anti-SARS-CoV-2 spike glycoprotein antibodies comprise a human IgG heavy chain constant region of an IgG1 or IgG4 isotype; or said 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 said 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;
(c) the first antigen-binding molecule is a first anti-SARS-CoV-2 spike glycoprotein antibody or antigen-binding fragment thereof, the first anti-SARS-CoV-2 spike glycoprotein antibody or antigen-binding fragment comprising an HCVR/LCVR amino acid sequence pair comprising the amino acid sequence of SEQ ID NO:2/10; and the second antigen-binding molecule is a second anti-SARS-CoV-2 spike glycoprotein antibody or antigen-binding fragment thereof, the second anti-SARS-CoV-2 spike glycoprotein antibody or antigen-binding fragment comprising an HCVR/LCVR amino acid sequence pair comprising the amino acid sequence of SEQ ID NO:22/30;
Optionally, said first and said second anti-SARS-CoV-2 spike glycoprotein antibodies comprise a human IgG heavy chain constant region; said first and said second anti-SARS-CoV-2 spike glycoprotein antibodies comprise a human IgG heavy chain constant region of the IgG1 or IgG4 isotype; or said 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 said 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; or (d) the first antigen-binding molecule is a first anti-SARS-CoV-2 spike glycoprotein antibody or antigen-binding fragment thereof that has the same binding and/or blocking properties as a reference antibody, the first antigen-binding molecule comprising an HCVR/LCVR amino acid sequence pair comprising the amino acid sequences of SEQ ID NOs: 2/10, and the second antigen-binding molecule is a second anti-SARS-CoV-2 spike glycoprotein antibody or antigen-binding fragment thereof that has the same binding and/or blocking properties as a reference antibody, the second antigen-binding molecule comprising an HCVR/LCVR amino acid sequence pair comprising the amino acid sequences of SEQ ID NOs: 22/30; or
(e) the first antigen-binding molecule is a first anti-SARS-CoV-2 spike glycoprotein antibody or antigen-binding fragment thereof having the same binding and/or blocking properties as a reference antibody, the first antigen-binding molecule comprising a heavy and light chain pair comprising the amino acid sequences of SEQ ID NO: 18/20, and the second antigen-binding molecule is a first anti-SARS-CoV-2 spike glycoprotein antibody or antigen-binding fragment thereof having the same binding and/or blocking properties as a reference antibody, the second antigen-binding molecule comprising a heavy and light chain pair comprising the amino acid sequences of SEQ ID NO: 38/4 ...

(a) 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-LCDR3, contained within a heavy chain variable region (HCVR) comprising the amino acid sequence of SEQ ID NO:42 and a light chain variable region (LCVR) comprising the amino acid sequence of SEQ ID NO:50, and optionally (i) the anti-SARS-CoV-2 spike glycoprotein antibody comprises a human IgG heavy chain constant region;
(ii) the anti-SARS-CoV-2 spike glycoprotein antibody comprises a human heavy chain constant region of the IgG1 or IgG4 isotype; or
(iii) 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; or (b) the antigen binding molecule is an anti-SARS-CoV-2 spike glycoprotein antibody or antigen-binding fragment thereof, wherein the anti-SARS-CoV-2 spike glycoprotein antibody or antigen-binding fragment comprises six complementarity determining regions, HCDR1-HCDR2-HCDR3-LCDR1-LCDR2-LCDR3, comprising the amino acid sequences of SEQ ID NOs:44-46-48-52-34-54, respectively, and optionally (i) the anti-SARS-CoV-2 spike glycoprotein antibody comprises a human IgG heavy chain constant region;
(ii) the anti-SARS-CoV-2 spike glycoprotein antibody comprises a human heavy chain constant region of the IgG1 or IgG4 isotype; or (iii) 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; or (c) the antigen-binding molecule is an anti-SARS-CoV-2 spike glycoprotein antibody or antigen-binding fragment thereof, wherein the anti-SARS-CoV-2 spike glycoprotein antibody or antigen-binding fragment comprises an HCVR comprising the amino acid sequence of SEQ ID NO:42 and an LCVR comprising the amino acid sequence of SEQ ID NO:50, and optionally (i) the anti-SARS-CoV-2 spike glycoprotein antibody comprises a human IgG heavy chain constant region;
(ii) the anti-SARS-CoV-2 spike glycoprotein antibody comprises a human heavy chain constant region of the IgG1 or IgG4 isotype; or
(iii) 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; or (d) the antigen binding molecule is an anti-SARS-CoV-2 spike glycoprotein antibody having the same binding and/or blocking properties as a reference antibody comprising an HCVR/LCVR amino acid sequence pair comprising the amino acid sequences of SEQ ID NO:42/50; or (e) the antigen binding molecule is an anti-SARS-CoV-2 spike glycoprotein antibody having the same binding and/or blocking properties as a reference antibody comprising a heavy and light chain pair comprising the amino acid sequences of SEQ ID NO:56/58.

The therapeutic or prophylactic pharmaceutical composition according to any one of claims 1 to 8, wherein the composition contains 1 mg to 10 g of the antigen-binding molecule.

(a) the composition comprises about 1.2 g of mAb10933 and about 1.2 g of mAb10987, optionally further comprising about 1.2 g of mAb10985; or (b) the composition comprises about 150 mg of mAb10933 and about 150 mg of mAb10987, optionally further comprising about 150 mg of mAb10985; or (c) the composition comprises about 300 mg of mAb10933 and about 300 mg of mAb10987, optionally further comprising about 300 mg of mAb10985; or 8. The therapeutic or prophylactic pharmaceutical composition of any one of claims 1 to 7, wherein: (d) the composition comprises about 600 mg of mAb10933 and about 600 mg of mAb10987, optionally, the composition further comprises about 600 mg of mAb10985; or (e) the composition comprises 150 mg to 1200 mg of mAb10933 and 150 mg to 1200 mg of mAb10987, optionally, the composition further comprises 150 mg to 1200 mg of mAb10985.

The therapeutic or prophylactic pharmaceutical composition according to any one of claims 1 to 10, wherein the therapeutic or prophylactic pharmaceutical composition is administered to the subject by intravenous infusion or subcutaneous injection.

After 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; at least one point improvement in clinical status using a 7-point ordinal scale; a reduction or elimination of the need for supplemental oxygen; a reduction or elimination of the need for mechanical ventilation; prevention of COVID-19 related mortality: prevention of all-cause mortality; and a change in serum concentration of one or more disease-related biomarkers, and optionally, (a) the 7-point ordinal scale is:
[1] Death,
[2] Hospitalization requiring invasive mechanical ventilation or extracorporeal membrane oxygenation,
[3] Hospitalization requiring non-invasive ventilation or high-flow oxygen devices;
[4] Hospitalization requiring supplemental oxygen;
[5] Hospitalization requiring ongoing medical care (COVID-19 related or otherwise) but not requiring supplemental oxygen;
[6] hospitalization that no longer requires ongoing medical care, not requiring supplemental oxygen, and [7] not being hospitalized; and/or (b) the one or more efficacy parameters are measured 21 days after administration of a first dose of the therapeutic composition; and/or (c) the reduction from baseline in SARS-CoV-2 viral shedding is determined by real-time quantitative PCR (RT-qPCR) of a nasopharyngeal swab sample, a nasal sample, or a saliva sample, or the change in serum concentration of the one or more disease-related biomarkers is a change in C-reactive protein, lactate dehydrogenase, D-dimer, or ferritin.

3. The therapeutic pharmaceutical composition of claim 2, wherein the subject is an outpatient, and following administration of the therapeutic composition, the subject exhibits fewer than 5 COVID-19 related clinic visits, telemedicine visits, hospitalizations, and/or Intensive Care Unit (ICU) admissions, and optionally: (a) the fewer than 5 COVID-19 related clinic visits, telemedicine visits, hospitalizations, and/or Intensive Care Unit (ICU) admissions are exhibited by the subject within 29 days after administration of a first dose of the therapeutic composition; and/or (b) the subject exhibits fewer than 4, fewer than 3, fewer than 2, or fewer than 1 COVID-19 related clinic visit, telemedicine visit, hospitalization, and/or Intensive Care Unit (ICU) admissions.

The therapeutic pharmaceutical composition of claim 12 or 13, wherein the subject tests negative for SARS-CoV-2 within 2 days to 3 weeks after the first administration of the therapeutic composition, and optionally the negative SARS-CoV-2 test is determined by RT-qPCR of a nasopharyngeal swab sample, a nasal sample, or a saliva sample.

15. The therapeutic pharmaceutical composition of any one of claims 1, 2 and 4-14, wherein the therapeutic pharmaceutical composition is for use in combination with an additional therapeutic agent, optionally wherein (a) the additional therapeutic agent is an antiviral compound such as remdesivir, an IL-6 or IL-6R blocker such as tocilizumab or sarilumab, or a steroid; and/or (b) the additional therapeutic agent is administered prior to, after, or simultaneously with the therapeutic pharmaceutical composition.

The therapeutic or prophylactic pharmaceutical composition according to any one of claims 1 to 15, wherein the subject is seronegative for SARS-CoV-2 infection.

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 sequence of SEQ ID NO:2/10, and three HCDRS and three LCDRS contained within a HCVR and LCVR amino acid sequence pair comprising the amino acid sequence of SEQ ID NO:22/30, for improving one or more clinical parameters of SARS-CoV-2 infection in a subject having SARS-CoV-2 infection.
and a second anti-SARS-CoV-2 spike glycoprotein antibody or antigen-binding fragment thereof comprising a first CDR and three LCDRs,
(a) the therapeutic pharmaceutical composition, when administered to a seronegative subject population, more rapidly alleviates at least one symptom of SARS-CoV-2 infection compared to a comparable seronegative subject population administered a placebo; or
(b) the therapeutic pharmaceutical composition, when administered to a seronegative subject population, more rapidly alleviates at least one symptom of SARS-CoV-2 infection compared to a comparable seropositive subject population; or (c) the therapeutic pharmaceutical composition reduces viral load in a subject population by 7 days after administration (day 7) compared to the day of administration (day 0), and optionally (i) the time weighted mean change from baseline nasopharyngeal (NP) viral load by day 7 in a seronegative subject population is at least 0.86 log10 copies/mL greater reduction (p<0.0001) 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 compared to a comparable subject population treated with placebo; or (ii) the change from baseline nasopharyngeal (NP) viral load by day 7 in a seronegative subject population is at least a 1.04 log10 copies/mL greater reduction (p<0.0001) in patients treated with 1.2 g of said first anti-SARS-CoV-2 spike glycoprotein antibody and 1.2 g of said second anti-SARS-CoV-2 spike glycoprotein antibody compared to a comparable subject population treated with placebo; or (iii) the mean change from baseline nasopharyngeal (NP) viral load by day 7 in said subject population is at least a 0.71 log10 copies/mL greater reduction (p<0.0001) in patients treated with 0.6 g of said first anti-SARS-CoV-2 spike glycoprotein antibody and 0.6 g of said second anti-SARS-CoV-2 spike glycoprotein antibody compared to a comparable subject population treated with placebo; or (iv) the mean change from baseline nasopharyngeal (NP) viral load by day 7 in said subject population is a 0.86 log10 copy/mL greater reduction (p<0.0001) in patients treated with 1.2 g of said first anti-SARS-CoV-2 spike glycoprotein antibody and 1.2 g of said second anti-SARS-CoV-2 spike glycoprotein antibody compared to a comparable subject population treated with a placebo; or (d) the therapeutic pharmaceutical composition reduces viral load in a subject population, and optionally (i) administering the therapeutic pharmaceutical 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, wherein the administering results in a mean reduction in viral load on day 7 after administration compared to a baseline viral load measured on day 0 prior to administration of at least 3.00 log10 copies/mL, and further optionally, the reduction is at least 3.50 log10 copies/mL; the reduction is at least 3.90 log10 copies/mL; the reduction is at least 3.75 log10 copies/mL; or the reduction is at least 4.09 log10 copies/mL; or (ii) administering the 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, wherein the administering results in a mean reduction in viral load on day 7 after administration compared to a baseline viral load measured on day 0 prior to administration of at least 3.50 log copies/mL;
Further optionally, the subject and/or subject population includes subjects who are not hospitalized with COVID-19; or
(e) the therapeutic pharmaceutical composition reduces the production of 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, compared to a comparable subject population treated with a placebo;
A therapeutic pharmaceutical composition that reduces the time to symptom alleviation (defined as mild or absent symptoms) by a median of 4 days in a subject population treated with a CoV-2 spike glycoprotein antibody, optionally wherein said subjects and/or subject population include subjects who are not hospitalized with COVID-19.