# US 11,999,799 B2 · Anti-TMPRSS2 antibodies and antigen-binding fragments

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- Number: US 11,999,799 B2
- Document ID: US11999799B2
- Status: Granted
- Kind: B2
- Application number: 17/171,941
- Filed: 2021-02-09
- Published: 2021-08-12
- Granted: 2024-06-04
- Earliest claimed: 2020-02-10
- Assignees: Regeneron Pharmaceuticals, Inc.
- Applicants: Regeneron Pharmaceuticals, Inc.
- Inventors: Alina Baum; Christos Kyratsous; Lisa Purcell
- Web page: https://patentgrep.com/patent/US11999799B2

## CPC

- C07K 16/40: against enzymes
- A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines}
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 31/14: for RNA viruses
- A61P 31/16: for influenza or rhinoviruses
- C07K 16/108: Orthomyxoviridae (F), e.g. influenza virus
- C12N 9/50: Proteinases {, e.g. Endopeptidases (3.4.21-3.4.25)}
- A61K 2039/505: {comprising antibodies}
- A61K 2039/507: {Comprising a combination of two or more separate antibodies}
- C07K 2317/21: from primates, e.g. man
- C07K 2317/31: multispecific
- C07K 2317/33: Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- C07K 2317/94: Stability, e.g. half-life, pH, temperature or enzyme-resistance
- 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)
- 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
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

The present disclosure provides antibodies and antigen-binding fragments thereof that bind specifically to TMPRSS2 and methods of using such antibodies and fragments for treating or preventing viral infections (e.g., coronavirus infections or influenza virus infections).

## Claims

### Claim 1

An isolated recombinant antibody or antigen-binding fragment thereof that specifically binds to human transmembrane protease, serine 2 (TMPRSS2), wherein the antibody comprises:
(i) three heavy chain complementarity determining regions (CDRs) (CDR-H1, CDR-H2, and CDR-H3) contained within a heavy chain variable region (HCVR) comprising SEQ ID NO: 2; and three light chain CDRs (CDR-L1, CDR-L2, and CDR-L3) contained within a light chain variable region (LCVR) comprising SEQ ID NO: 10; or
(ii) three heavy chain CDRs (CDR-H1, CDR-H2, and CDR-H3) contained within an HCVR comprising SEQ ID NO: 22; and three light chain CDRs (CDR-L1, CDR-L2, and CDR-L3) contained within an LCVR comprising SEQ ID NO: 30; or
(iii) three heavy chain CDRs (CDR-H1, CDR-H2, and CDR-H3) contained within an HCVR comprising SEQ ID NO: 42; and three light chain CDRs (CDR-L1, CDR-L2, and CDR-L3) contained within an LCVR comprising SEQ ID NO: 50.

### Claim 2 (depends on 1)

The antibody or antigen-binding fragment thereof of claim 1, wherein said antibody or antigen-binding fragment thereof comprises an HCVR comprising SEQ ID NO: 2; and an LCVR comprising SEQ ID NO: 10.

### Claim 3 (depends on 1)

The antibody or antigen-binding fragment thereof of claim 1, comprising:
(a) an HCVR comprising the CDR-H1, CDR-H2, and CDR-H3 of an immunoglobulin heavy chain that comprises SEQ ID NO: 2; and
(b) an LCVR comprising the CDR-L1, CDR-L2, and CDR-L3 of an immunoglobulin light chain that comprises SEQ ID NO: 10.

### Claim 4 (depends on 1)

The antibody or antigen-binding fragment thereof of claim 1, comprising:
an HCVR that comprises:
(a) a CDR-H1 comprising SEQ ID NO: 4,
(b) a CDR-H2 comprising SEQ ID NO: 6, and
(c) a CDR-H3 comprising SEQ ID NO: 8; and
an LCVR that comprises:
(a) a CDR-L1 comprising SEQ ID NO: 12,
(b) a CDR-L2 comprising SEQ ID NO: 14, and
(c) a CDR-L3 comprising SEQ ID NO: 16.

### Claim 5 (depends on 4)

The antibody or antigen-binding fragment thereof of claim 4, comprising:
(a) an HCVR comprising at least 90% amino acid sequence identity to SEQ ID NO: 2; and
(b) an LCVR comprising at least 90% amino acid sequence identity to SEQ ID NO: 10.

### Claim 6 (depends on 1)

The antibody or antigen-binding fragment thereof of claim 1, comprising:
(a) a heavy chain immunoglobulin that comprises SEQ ID NO: 18;
and
(b) a light chain immunoglobulin that comprises SEQ ID NO: 20.

### Claim 7 (depends on 1)

The antibody or antigen-binding fragment thereof of claim 1, wherein said antibody or antigen-binding fragment comprises an HCVR comprising SEQ ID NO: 22; and an LCVR comprising ID NO: 30.

### Claim 8 (depends on 1)

The antibody or antigen-binding fragment thereof of claim 1, comprising:
(a) an HCVR comprising the CDR-H1, CDR-H2, and CDR-H3 of an immunoglobulin heavy chain that comprises SEQ ID NO: 22; and
(b) an LCVR comprising the CDR-L1, CDR-L2, and CDR-L3 of an immunoglobulin light chain that comprises SEQ ID NO: 30.

### Claim 9 (depends on 1)

The antibody or antigen-binding fragment thereof of claim 1, comprising:
an HCVR that comprises:
(a) a CDR-H1 comprising SEQ ID NO: 24,
(b) a CDR-H2 comprising SEQ ID NO: 26, and
(c) a CDR-H3 comprising SEQ ID NO: 28; and
an LCVR that comprises:
(a) a CDR-L1 comprising SEQ ID NO: 32,
(b) a CDR-L2 comprising SEQ ID NO: 34, and
(c) a CDR-L3 comprising SEQ ID NO: 36.

### Claim 10 (depends on 9)

The antibody or antigen-binding fragment thereof of claim 9, comprising:
(a) an HCVR comprising at least 90% amino acid sequence identity to SEQ ID NO: 22; and
(b) an LCVR comprising at least 90% amino acid sequence identity to SEQ ID NO: 30.

### Claim 11 (depends on 1)

The antibody or antigen-binding fragment thereof of claim 1, comprising:
(a) a heavy chain immunoglobulin that comprises SEQ ID NO: 38;
and
(b) a light chain immunoglobulin that comprises SEQ ID NO: 40.

### Claim 12 (depends on 1)

The antibody or antigen-binding fragment thereof of claim 1, wherein said antibody or antigen-binding fragment comprises SEQ ID NO: 42; and an LCVR comprising SEQ ID NO: 50.

### Claim 13 (depends on 1)

The antibody or antigen-binding fragment thereof of claim 1, comprising:
(a) an HCVR comprising the CDR-H1, CDR-H2, and CDR-H3 of an immunoglobulin heavy chain that comprises SEQ ID NO: 42; and
(b) an LCVR comprising the CDR-L1, CDR-L2, and CDR-L3 of an immunoglobulin light chain that comprises SEQ ID NO: 50.

### Claim 14 (depends on 1)

The antibody or antigen-binding fragment thereof of claim 1, comprising:
an HCVR that comprises:
(a) a CDR-H1 comprising SEQ ID NO: 44,
(b) a CDR-H2 comprising SEQ ID NO: 46, and
(c) a CDR-H3 comprising SEQ ID NO: 48; and
an LCVR that comprises:
(a) a CDR-L1 comprising SEQ ID NO: 52,
(b) a CDR-L2 comprising SEQ ID NO: 54, and
(c) a CDR-L3 comprising SEQ ID NO: 56.

### Claim 15 (depends on 14)

The antibody or antigen-binding fragment thereof of claim 14, comprising:
(a) an HCVR comprising at least 90% amino acid sequence identity to SEQ ID NO: 42; and
(b) an LCVR comprising at least 90% amino acid sequence identity to SEQ ID NO: 50.

### Claim 16 (depends on 1)

The antibody or antigen-binding fragment of claim 1, comprising:
(a) a heavy chain immunoglobulin that comprises SEQ ID NO: 58;
and
(b) a light chain immunoglobulin that comprises SEQ ID NO: 60, or an LCVR that comprises SEQ ID NO: 50.

### Claim 17 (depends on 1)

The antibody or antigen-binding fragment thereof of claim 1 which is multispecific.

### Claim 18 (depends on 1)

The antibody or antigen-binding fragment thereofof claim 1 which comprises one or more of the following properties:
a) inhibits growth of coronavirus in TMPRSS2-expressing cells;
b) inhibits growth of influenza virus in TMPRSS2-expressing cells;
c) binds to the surface of TMPRSS-expressing cells;
d) does not significantly bind to MDCK/Tet-on cells which do not express TMPRSS2;
e) limits spread of coronavirus infection of cells in vitro;
f) limits spread of influenza virus infection of cells in vitro;
g) protects mice engineered to express the human TMPRSS2 protein from death and/or weight loss caused by coronavirus infection; and
h) protects mice engineered to express the human TMPRSS2 protein from death caused by influenza virus infection.

### Claim 19 (depends on 1)

A complex comprising the antibody or antigen-binding fragment thereof of claim 1 bound to a TMPRSS2 polypeptide.

### Claim 20 (depends on 1)

A method for making the antibody or antigen-binding fragment thereof of claim 1, comprising:
(a) introducing into a host cell one or more polynucleotides encoding said antibody or antigen-binding fragment; and
(b) culturing the host cell under conditions favorable to expression of the one or more polynucleotides.

### Claim 21 (depends on 20)

The method of claim 20, further comprising:
(c) isolating the antibody or antigen-binding fragment thereof from the host cell and/or a medium in which the host cell is grown.

### Claim 22 (depends on 20)

The method of claim 20, wherein the host cell is a Chinese hamster ovary cell.

### Claim 23 (depends on 20)

An antibody or antigen-binding fragment thereof which is a product of the method of claim 20.

### Claim 24

A polypeptide pair comprising:
(a) a CDR-H1, a CDR-H2, and a CDR-H3 of a V H domain of an antibody or antigen-binding fragment thereof that comprises SEQ ID NO: 2 and a CDR-L1, a CDR-L2, and a CDR-L3 of a V L domain of an immunoglobulin chain that comprises SEQ ID NO: 10;
(b) a CDR-H1, a CDR-H2, and a CDR-H3 of a V H domain of an antibody or antigen-binding fragment thereof that comprises SEQ ID NO: 22 and a CDR-L1, a CDR-L2, and a CDR-L3 of a V L domain of an immunoglobulin chain that comprises SEQ ID NO: 30; or
(c) a CDR-H1, a CDR-H2, and a CDR-H3 of a V H domain of an antibody or antigen-binding fragment thereof that comprises SEQ ID NO: 42 and a CDR-L1, a CDR-L2, and a CDR-L3 of a V L domain of an immunoglobulin chain that comprises SEQ ID NO: 50.

### Claim 25

A composition comprising:
(i) a first polynucleotide encoding a polypeptide comprising (a) a CDR-H1 comprising SEQ ID NO: 4, (b) a CDR-H2 comprising SEQ ID NO: 6, and (c) a CDR-H3 comprising SEQ ID NO: 8; and a second polynucleotide encoding a polypeptide comprising (a) a CDR-L1 comprising SEQ ID NO: 12, (b) a CDR-L2 comprising SEQ ID NO: 14, and (c) a CDR-L3 comprising SEQ ID NO: 16;
(ii) a first polynucleotide encoding a polypeptide comprising (a) a CDR-H1 comprising SEQ ID NO: 24, (b) a CDR-H2 comprising SEQ ID NO: 26, and (c) a CDR-H3 comprising SEQ ID NO: 28; and a second polynucleotide encoding a polypeptide comprising (a) a CDR-L1 comprising SEQ ID NO: 32, (b) a CDR-L2 comprising SEQ ID NO: 34, and (c) a CDR-L3 comprising SEQ ID NO: 36; or
(iii) a first polynucleotide encoding a polypeptide comprising (a) a CDR-H1 comprising SEQ ID NO: 44, (b) a CDR-H2 comprising SEQ ID NO: 46, and (c) a CDR-H3 comprising SEQ ID NO: 48; and a second polynucleotide encoding a polypeptide comprising (a) a CDR-L1 comprising SEQ ID NO: 52, (b) a CDR-L2 comprising SEQ ID NO: 54, and (c) a CDR-L3 comprising SEQ ID NO: 56.

### Claim 26

A vector comprising:
(i) a first polynucleotide encoding a polypeptide comprising (a) a CDR-H1 comprising SEQ ID NO: 4, (b) a CDR-H2 comprising SEQ ID NO: 6, and (c) a CDR-H3 comprising SEQ ID NO: 8; and a second polynucleotide encoding a polypeptide comprising (a) a CDR-L1 comprising SEQ ID NO: 12, (b) a CDR-L2 comprising SEQ ID NO: 14, and (c) a CDR-L3 comprising SEQ ID NO: 16;
(ii) a first polynucleotide encoding a polypeptide comprising (a) a CDR-H1 comprising SEQ ID NO: 4, (b) a CDR-H2 comprising SEQ ID NO: 6, and (c) a CDR-H3 comprising SEQ ID NO: 8; and a second polynucleotide encoding a polypeptide comprising (a) a CDR-L1 comprising SEQ ID NO: 12, (b) a CDR-L2 comprising SEQ ID NO: 14, and (c) a CDR-L3 comprising SEQ ID NO: 16; or
(iii) a first polynucleotide encoding a polypeptide comprising (a) a CDR-H1 comprising SEQ ID NO: 44, (b) a CDR-H2 comprising SEQ ID NO: 46, and (c) a CDR-H3 comprising SEQ ID NO: 48; and a second polynucleotide encoding a polypeptide comprising (a) a CDR-L1 comprising SEQ ID NO: 52, (b) a CDR-L2 comprising SEQ ID NO: 54, and (c) a CDR-L3 comprising SEQ ID NO: 56.

### Claim 27 (depends on 26)

A host cell comprising the vector of claim 26.

### Claim 28 (depends on 1)

A composition or kit comprising the antibody or antigen-binding fragment thereof of claim 1.

### Claim 29 (depends on 1)

A pharmaceutical composition comprising the antibody or antigen-binding fragment thereof of claim 1 and a pharmaceutically acceptable carrier.

### Claim 30 (depends on 29)

The pharmaceutical composition of claim 29, further comprising a therapeutic agent selected from the group consisting of an anti-viral drug, a vaccine, an antibody or antigen-binding fragment thereof that binds to influenza Group I HA protein, and an antibody or antigen-binding fragment thereof that binds to influenza Group II HA protein.

### Claim 31 (depends on 28)

The composition or kit of claim 28, comprising a further therapeutic agent selected from the group consisting of an anti-viral drug, a vaccine, an antibody or antigen-binding fragment thereof that binds to influenza Group I HA protein, and an antibody or antigen-binding fragment thereof that binds to influenza Group II HA protein.

### Claim 32 (depends on 31)

The composition or kit of claim 31 wherein the further therapeutic agent is a member selected from the group consisting of: remdesivir, chloroquine, lopinavir, ritonavir, ribavirin, ledipasvir, sofosbuvir, a combination of ledipasvir and sofosbuvir, oseltamivir, zanamivir, ribavirin and interferon-alpha2b, interferon-alpha2a, an anti-cancer agent, and an antibody or antigen-binding fragment thereof that specifically binds to influenza HA or coronavirus spike protein; and/or
an antibody or antigen binding fragment thereof selected from the group consisting of H1H11723P; H1H11729P; H1H11820N; H1H11829N; H1H11829N2; H2aM11829N; H2M11830N; H1H11830N2; H1H11903N; H1H14571N; H2a14571N; H1H11704P; H1H11711P; H1H11714P; H1H11717P; H1H11724P; H1H11727P; H1H11730P2; H1H11731P2; H1H11734P2; H1H11736P2; H1H11742P2; H1H11744P2; H1H11745P2; H1H11747P2; H1H11748P2; H1H17952B; H1H17953B; H1H17954B; H1H17955B; H1H17956B; H1H17957B; H1H17958B; H1H17959B; H1H17960B; H1H17961B; H1H17962B; H1H17963B; H1H17964B; H1H17965B; H1H17966B; H1H17967B; H1H17968B; H1H17969B; H1H17970B; H1H17971B; H1H17972B; H1H17973B; H1H17974B; H1H17975B; H1H17976B; H1H17977B; H1H17978B; H1H17979B; H1H17980B; H1H17981B; H1H17982B; H1H17983B; H1H17984B; H1H17985B; H1H17986B; H1H17987B; H1H17988B; H1H17989B; H1H17990B; H1H17991B; H1H17992B; H1H17993B; H1H17994B; H1H17995B; H1H17996B; H1H17997B; H1H17998B; H1H17999B; H1H18000B; H1H18001B; H1H18002B; H1H18003B; H1H18004B; H1H18005B; H1H18006B; H1H18007B; H1H18008B; H1H18009B; H1H18010B; H1H18011B; H1H18012B; H1H18013B; H1H18014B; H1H18015B; H1H18016B; H1H18017B; H1H18018B; H1H18019B; H1H18020B; H1H18021B; H1H18022B; H1H18023B; H1H18024B; H1H18025B; H1H18026B; H1H18027B; H1H18028B; H1H18029B; H1H18030B; H1H18031B; H1H18032B; H1H18033B; H1H18034B; H1H18035B; H1H18037B; H1H18038B; H1H18039B; H1H18040B; H1H18041B; H1H18042B; H1H18043B; H1H18044B; H1H18045B; H1H18046B; H1H18047B; H1H18048B; H1H18049B; H1H18051B; H1H18052B; H1H18053B; H1H18054B; H1H18055B; H1H18056B; H1H18057B; H1H18058B; H1H18059B; H1H18060B; H1H18061B; H1H18062B; H1H18063B; H1H18064B; H1H18065B; H1H18066B; H1H18067B; H1H18068B; H1H18069B; H1H18070B; H1H18071B; H1H18072B; H1H18073B; H1H18074B; H1H18075B; H1H18076B; H1H18077B; H1H18078B; H1H18079B; H1H18080B; H1H18081B; H1H18082B; H1H18083B; H1H18084B; H1H18085B; H1H18086B; H1H18087B; H1H18088B; H1H18089B; H1H18090B; H1H18091B; H1H18092B; H1H18093B; H1H18094B; H1H18095B; H1H18096B; H1H18097B; H1H18098B; H1H18099B; H1H18100B; H1H18101B; H1H18102B; H1H18103B; H1H18104B; H1H18105B; H1H18107B; H1H18108B; H1H18109B; H1H18110B; H1H18111B; H1H18112B; H1H18113B; H1H18114B; H1H18115B; H1H18116B; H1H18117B; H1H18118B; H1H18119B; H1H18120B; H1H18121B; H1H18122B; H1H18123B; H1H18124B; H1H18125B; H1H18126B; H1H18127B; H1H18128B; H1H18129B; H1H18130B; H1H18131B; H1H18132B; H1H18133B; H1H18134B; H1H18135B; H1H18136B; H1H18137B; H1H18138B; H1H18139B; H1H18140B; H1H18141B; H1H18142B; H1H18143B; H1H18144B; H1H18145B; H1H18146B; H1H18147B; H1H18148B; H1H18149B; H1H18150B; H1H18151B; H1H18152B; H1H18153B; H1H18154B; H1H18155B; H1H18156B; H1H18157B; H1H18158B; H1H18159B; H1H18160B; H1H18161B; H1H18162B; H1H18163B; H1H18164B; H1H18165B; H1H18166B; H1H18167B; H1H18168B; H1H18169B; H1H18170B; H1H18171B; H1H18172B; H1H18173B; H1H18174B; H1H18175B; H1H18176B; H1H18177B; H1H18178B; H1H18179B; H1H18180B; H1H18181B; H1H18182B; H1H18183B; H1H18184B; H1H18185B; H1H18186B; H1H18187B; H1H18188B; H1H18189B; H1H18190B; H1H18191B; H1H18192B; H1H18193B; H1H18194B; H1H18195B; H1H18196B; H1H18197B; H1H18198B; H1H18199B; H1H18200B; H1H18201B; H1H18202B; H1H18203B; H1H18204B; H1H18205B; H1H18206B; H1H18207B; H1H18208B; H1H18209B; H1H18210B; H1H18211B; H1H18212B; H1H18213B; H1H18214B; H1H18216B; H1H18217B; H1H18218B; H1H18219B; H1H18220B; H1H18221B; H1H18222B; H1H18223B; H1H18224B; H1H18225B; H1H18226B; H1H18227B; H1H18228B; H1H18229B; H1H18230B; H1H18231B; H1H18232B; H1H18233B; H1H18234B; H1H18235B; H1H18236B; H1H18237B; H1H18238B; H1H18239B; H1H18240B; H1H18241B; H1H18242B; H1H18243B; H1H18244B; H1H18245B; H1H18246B; H1H18247B; H1H18248B; H1H18249B; H1H18250B; H1H18251B; H1H18252B; H1H18253B; H1H18254B; H1H18255B; H1H18256B; H1H18257B; H1H18258B; H1H18259B; H1H18261B; H1H18262B; H1H18263B; H1H18264B; H1H18265B; H1H18266B; H1H18267B; H1H18268B; H1H18269B; H1H18270B; H1H18271B; H1H18272B; H1H18274B; H1H18275B; H1H18276B; H1H18277B; H1H18278B; H1H18279B; H1H18280B; H1H18281B; H1H18282B; H1H18283B; H1H18284B; H1H18285B; H1H18286B; H1H18287B; H1H18288B; H1H18289B; H1H18290B; H1H18291B; H1H18292B; H1H18293B; H1H18294B; H1H18295B; H1H18297B; H1H18298B; H1H18299B; H1H18300B; H1H18301B; H1H18302B; H1H18303B; H1H18304B; H1H18305B; H1H18306B; H1H18307B; H1H18308B; H1H18309B; H1H18310B; H1H18311B; H1H18312B; H1H18313B; H1H18314B; H1H18315B; H1H18316B; H1H18317B; H1H18318B; H1H18319B; H1H18320B; H1H18321B; H1H18322B; H1H18323B; H1H18324B; H1H18325B; H1H18326B; H1H18327B; H1H18328B; H1H18329B; H1H18330B; H1H18331B; H1H18332B; H1H18333B; H1H18334B; H1H18335B; H4sH15188P; H1H15188P; H1H15211P; H1H15177P; H4sH15211P; H1H15260P2; H1H15259P2; H1H15203P; H4sH15260P2; H4sH15231P2; H1H15237P2; H1H15208P; H1H15228P2; H1H15233P2; H1H15264P2; H1H15231P2; H1H15253P2; H1H15215P; and H1H15249P2.

### Claim 33 (depends on 1)

A vessel or injection device comprising the antibody or antigen-binding fragment thereof of claim 1.

### Claim 34 (depends on 1)

A method for treating prostate, renal, or pancreatic cancer or infection with an influenza virus, coronavirus, SARS-CoV, MERS-CoV, SARS-CoV-2, or parainfluenza virus in a subject in need thereof, comprising administering a therapeutically effective amount of the antibody or antigen-binding fragment thereof of claim 1.

### Claim 35 (depends on 34)

The method of claim 34, wherein the subject is administered one or more further therapeutic agents selected from the group consisting of an anti-viral drug, a vaccine, an antibody or antigen-binding fragment thereof that binds to influenza Group I HA protein, and an antibody or antigen-binding fragment thereof that binds to influenza Group II HA protein.

### Claim 36 (depends on 35)

The method of claim 35, wherein the subject is administered one or more further therapeutic agents which is an anti-viral drug or a vaccine.

### Claim 37 (depends on 35)

The method of claim 35, wherein the subject is administered one or more further therapeutic agents which is a member selected from the group consisting of: remdesivir, chloroquine, lopinavir, ritonavir, ribavirin, ledipasvir, sofosbuvir, a combination of ledipasvir and sofosbuvir, oseltamivir, zanamivir, ribavirin and interferon-alpha2b, interferon-alpha2a, and an antibody or antigen-binding fragment thereof that specifically binds to influenza HA or coronavirus spike protein; and/or an antibody or antigen binding fragment thereof selected from the group consisting of H1H11723P; H1H11729P; H1H11820N; H1H11829N; H1H11829N2; H2aM11829N; H2M11830N; H1H11830N2; H1H11903N; H1H14571N; H2a14571N; H1H11704P; H1H11711P; H1H11714P; H1H11717P; H1H11724P; H1H11727P; H1H11730P2; H1H11731P2; H1H11734P2; H1H11736P2; H1H11742P2; H1H11744P2; H1H11745P2; H1H11747P2; H1H11748P2; H1H17952B; H1H17953B; H1H17954B; H1H17955B; H1H17956B; H1H17957B; H1H17958B; H1H17959B; H1H17960B; H1H17961B; H1H17962B; H1H17963B; H1H17964B; H1H17965B; H1H17966B; H1H17967B; H1H17968B; H1H17969B; H1H17970B; H1H17971B; H1H17972B; H1H17973B; H1H17974B; H1H17975B; H1H17976B; H1H17977B; H1H17978B; H1H17979B; H1H17980B; H1H17981B; H1H17982B; H1H17983B; H1H17984B; H1H17985B; H1H17986B; H1H17987B; H1H17988B; H1H17989B; H1H17990B; H1H17991B; H1H17992B; H1H17993B; H1H17994B; H1H17995B; H1H17996B; H1H17997B; H1H17998B; H1H17999B; H1H18000B; H1H18001B; H1H18002B; H1H18003B; H1H18004B; H1H18005B; H1H18006B; H1H18007B; H1H18008B; H1H18009B; H1H18010B; H1H18011B; H1H18012B; H1H18013B; H1H18014B; H1H18015B; H1H18016B; H1H18017B; H1H18018B; H1H18019B; H1H18020B; H1H18021B; H1H18022B; H1H18023B; H1H18024B; H1H18025B; H1H18026B; H1H18027B; H1H18028B; H1H18029B; H1H18030B; H1H18031B; H1H18032B; H1H18033B; H1H18034B; H1H18035B; H1H18037B; H1H18038B; H1H18039B; H1H18040B; H1H18041B; H1H18042B; H1H18043B; H1H18044B; H1H18045B; H1H18046B; H1H18047B; H1H18048B; H1H18049B; H1H18051B; H1H18052B; H1H18053B; H1H18054B; H1H18055B; H1H18056B; H1H18057B; H1H18058B; H1H18059B; H1H18060B; H1H18061B; H1H18062B; H1H18063B; H1H18064B; H1H18065B; H1H18066B; H1H18067B; H1H18068B; H1H18069B; H1H18070B; H1H18071B; H1H18072B; H1H18073B; H1H18074B; H1H18075B; H1H18076B; H1H18077B; H1H18078B; H1H18079B; H1H18080B; H1H18081B; H1H18082B; H1H18083B; H1H18084B; H1H18085B; H1H18086B; H1H18087B; H1H18088B; H1H18089B; H1H18090B; H1H18091B; H1H18092B; H1H18093B; H1H18094B; H1H18095B; H1H18096B; H1H18097B; H1H18098B; H1H18099B; H1H18100B; H1H18101B; H1H18102B; H1H18103B; H1H18104B; H1H18105B; H1H18107B; H1H18108B; H1H18109B; H1H18110B; H1H18111B; H1H18112B; H1H18113B; H1H18114B; H1H18115B; H1H18116B; H1H18117B; H1H18118B; H1H18119B; H1H18120B; H1H18121B; H1H18122B; H1H18123B; H1H18124B; H1H18125B; H1H18126B; H1H18127B; H1H18128B; H1H18129B; H1H18130B; H1H18131B; H1H18132B; H1H18133B; H1H18134B; H1H18135B; H1H18136B; H1H18137B; H1H18138B; H1H18139B; H1H18140B; H1H18141B; H1H18142B; H1H18143B; H1H18144B; H1H18145B; H1H18146B; H1H18147B; H1H18148B; H1H18149B; H1H18150B; H1H18151B; H1H18152B; H1H18153B; H1H18154B; H1H18155B; H1H18156B; H1H18157B; H1H18158B; H1H18159B; H1H18160B; H1H18161B; H1H18162B; H1H18163B; H1H18164B; H1H18165B; H1H18166B; H1H18167B; H1H18168B; H1H18169B; H1H18170B; H1H18171B; H1H18172B; H1H18173B; H1H18174B; H1H18175B; H1H18176B; H1H18177B; H1H18178B; H1H18179B; H1H18180B; H1H18181B; H1H18182B; H1H18183B; H1H18184B; H1H18185B; H1H18186B; H1H18187B; H1H18188B; H1H18189B; H1H18190B; H1H18191B; H1H18192B; H1H18193B; H1H18194B; H1H18195B; H1H18196B; H1H18197B; H1H18198B; H1H18199B; H1H18200B; H1H18201B; H1H18202B; H1H18203B; H1H18204B; H1H18205B; H1H18206B; H1H18207B; H1H18208B; H1H18209B; H1H18210B; H1H18211B; H1H18212B; H1H18213B; H1H18214B; H1H18216B; H1H18217B; H1H18218B; H1H18219B; H1H18220B; H1H18221B; H1H18222B; H1H18223B; H1H18224B; H1H18225B; H1H18226B; H1H18227B; H1H18228B; H1H18229B; H1H18230B; H1H18231B; H1H18232B; H1H18233B; H1H18234B; H1H18235B; H1H18236B; H1H18237B; H1H18238B; H1H18239B; H1H18240B; H1H18241B; H1H18242B; H1H18243B; H1H18244B; H1H18245B; H1H18246B; H1H18247B; H1H18248B; H1H18249B; H1H18250B; H1H18251B; H1H18252B; H1H18253B; H1H18254B; H1H18255B; H1H18256B; H1H18257B; H1H18258B; H1H18259B; H1H18261B; H1H18262B; H1H18263B; H1H18264B; H1H18265B; H1H18266B; H1H18267B; H1H18268B; H1H18269B; H1H18270B; H1H18271B; H1H18272B; H1H18274B; H1H18275B; H1H18276B; H1H18277B; H1H18278B; H1H18279B; H1H18280B; H1H18281B; H1H18282B; H1H18283B; H1H18284B; H1H18285B; H1H18286B; H1H18287B; H1H18288B; H1H18289B; H1H18290B; H1H18291B; H1H18292B; H1H18293B; H1H18294B; H1H18295B; H1H18297B; H1H18298B; H1H18299B; H1H18300B; H1H18301B; H1H18302B; H1H18303B; H1H18304B; H1H18305B; H1H18306B; H1H18307B; H1H18308B; H1H18309B; H1H18310B; H1H18311B; H1H18312B; H1H18313B; H1H18314B; H1H18315B; H1H18316B; H1H18317B; H1H18318B; H1H18319B; H1H18320B; H1H18321B; H1H18322B; H1H18323B; H1H18324B; H1H18325B; H1H18326B; H1H18327B; H1H18328B; H1H18329B; H1H18330B; H1H18331B; H1H18332B; H1H18333B; H1H18334B; H1H18335B; H4sH15188P; H1H15188P; H1H15211P; H1H15177P; H4sH15211P; H1H15260P2; H1H15259P2; H1H15203P; H4sH15260P2; H4sH15231P2; H1H15237P2; H1H15208P; H1H15228P2; H1H15233P2; H1H15264P2; H1H15231P2; H1H15253P2; H1H15215P; and H1H15249P2.

### Claim 38 (depends on 1)

A method for administering the antibody or antigen-binding fragment thereof of claim 1 into the body of a subject comprising injecting the antibody or antigen-binding fragment thereof into the body of the subject.

### Claim 39 (depends on 38)

The method of claim 38, wherein the antibody or antigen-binding fragment thereof is injected into the body of the subject subcutaneously, intravenously or intramuscularly.

### Claim 40 (depends on 1)

The antibody or antigen-binding fragment thereof of claim 1, which binds to TMPRSS2 with an EC50 of less than about 10−9 M.

### Claim 41 (depends on 1)

The antibody or antigen-binding fragment thereof of claim 1, which demonstrates an increase in survival in a coronavirus-infected animal after administration to said coronavirus-infected animal, as compared to a comparable coronavirus-infected animal without said administration.

### Claim 42 (depends on 4)

The antibody or antigen-binding fragment thereof of claim 4 which is an antibody comprising:
(i) a heavy chain comprising at least about 90% sequence identity to the heavy chain comprising SEQ ID NO: 18; and a light chain comprising least about 90% sequence identity to the light chain comprising SEQ ID NO: 20.

### Claim 43 (depends on 9)

The antibody or antigen-binding fragment thereof of claim 9 which is an antibody comprising:
(ii) a heavy chain comprising at least about 90% sequence identity to the heavy chain comprising SEQ ID NO: 38; and a light chain comprising least about 90% sequence identity to the light chain comprising SEQ ID NO: 40.

### Claim 44 (depends on 14)

The antibody or antigen-binding fragment thereof of claim 14 which is an antibody comprising:
(iii) a heavy chain comprising at least about 90% sequence identity to the heavy chain comprising SEQ ID NO: 58; and a light chain comprising at least about 90% sequence identity to the light chain comprising SEQ ID NO: 60.