# US 10,246,519 B2 · NSP4 inhibitors and methods of use

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- Number: US 10,246,519 B2
- Document ID: US10246519B2
- Status: Granted
- Kind: B2
- Application number: 15/958,977
- Filed: 2018-04-20
- Published: 2018-12-27
- Granted: 2019-04-02
- Earliest claimed: 2013-10-11
- Assignees: Genentech, Inc.
- Applicants: Genentech, Inc.
- Inventors: Shuo-Yen Jack Lin; Daniel K. Kirchhofer; Menno Van Lookeren Campagne
- Web page: https://patentgrep.com/patent/US10246519B2

## CPC

- C07K 16/40: against enzymes
- A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 11/06: Antiasthmatics
- A61P 13/12: of the kidneys
- A61P 17/00: Drugs for dermatological disorders
- A61P 17/06: Antipsoriatics
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 27/02: Ophthalmic agents
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 31/04: Antibacterial agents
- A61P 35/00: Antineoplastic agents
- A61P 37/02: Immunomodulators
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- A61P 37/08: Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14)
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07K 16/24: against cytokines, lymphokines or interferons
- A61K 2039/505: {comprising antibodies}
- C07K 2317/14: Specific host cells or culture conditions, e.g. components, pH or temperature
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/33: Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
- C07K 2317/54: F(ab')2
- C07K 2317/55: Fab or Fab'
- C07K 2317/622: Single chain antibody (scFv)
- 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: 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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)

## Abstract

The invention provides NSP4 inhibitors (such as anti-NSP4 antibodies) and methods of using the same.

## Claims

### Claim 1

An isolated nucleic acid encoding an anti-NSP4 antibody comprising a heavy chain and a light chain, wherein the light chain comprises an HVR-L1 comprising the sequence of SEQ ID NO:19, an HVR-L2 comprising the sequence of SEQ ID NO:11, and an HVR-L3 comprising the sequence of SEQ ID NO:12; and wherein the heavy chain comprises
an HVR-H1 comprising the sequence of SEQ ID NO:56, an HVR-H2 comprising the sequence of SEQ ID NO:57, and an HVR-H3 comprising the sequence of SEQ ID NO:58.

### Claim 2 (depends on 1)

A host cell comprising the nucleic acid of claim 1.

### Claim 3 (depends on 2)

A method for producing an antibody comprising culturing the host cell of claim 2 under conditions suitable for production of the antibody.

### Claim 4 (depends on 3)

The method of claim 3, further comprising recovering the antibody produced by the host cell.

### Claim 5 (depends on 1)

A vector comprising the nucleic acid of claim 1.

### Claim 6 (depends on 1)

The isolated nucleic acid of claim 1, wherein the light chain comprises a light chain variable region comprising the sequence of SEQ ID NO:16.

### Claim 7 (depends on 1)

The isolated nucleic acid of claim 1, wherein the heavy chain comprises a heavy chain variable region comprising the sequence of SEQ ID NO: 80.

### Claim 8 (depends on 1)

The isolated nucleic acid of claim 1, wherein the antibody is an antibody fragment selected from the group consisting of a Fab, Fab′-SH, Fv, scFv, and (Fab′)2 fragment.

### Claim 9 (depends on 1)

The isolated nucleic acid of claim 1, wherein the antibody comprises a constant region of human IgG1, IgG2, IgG3, or IgG4.

### Claim 10

An isolated nucleic acid encoding an anti-NSP4 antibody comprising a heavy chain and a light chain, wherein the light chain comprises an HVR-L1 comprising the sequence of SEQ ID NO:19, an HVR-L2 comprising the sequence of SEQ ID NO:11, and an HVR-L3 comprising the sequence of SEQ ID NO:12; and wherein the heavy chain comprises an HVR-H1 comprising the sequence of SEQ ID NO:32, an HVR-H2 comprising the sequence of SEQ ID NO:33, and an HVR-H3 comprising the sequence of SEQ ID NO:34.

### Claim 11 (depends on 10)

A vector comprising the nucleic acid of claim 10.

### Claim 12 (depends on 10)

A host cell comprising the nucleic acid of claim 10.

### Claim 13 (depends on 12)

A method for producing an antibody comprising culturing the host cell of claim 12 under conditions suitable for production of the antibody.

### Claim 14 (depends on 13)

The method of claim 13, further comprising recovering the antibody produced by the host cell.

### Claim 15

An isolated nucleic acid encoding an anti-NSP4 antibody comprising a heavy chain and a light chain, wherein the light chain comprises an HVR-L1 comprising the sequence of SEQ ID NO:19, an HVR-L2 comprising the sequence of SEQ ID NO:11, and an HVR-L3 comprising the sequence of SEQ ID NO:12; and wherein the heavy chain comprises an HVR-H1 comprising the sequence of SEQ ID NO:38, an HVR-H2 comprising the sequence of SEQ ID NO:39, and an HVR-H3 comprising the sequence of SEQ ID NO:40.

### Claim 16 (depends on 15)

A vector comprising the nucleic acid of claim 15.

### Claim 17 (depends on 15)

A host cell comprising the nucleic acid of claim 15.

### Claim 18 (depends on 17)

A method for producing an antibody comprising culturing the host cell of claim 17 under conditions suitable for production of the antibody.

### Claim 19 (depends on 18)

The method of claim 18, further comprising recovering the antibody produced by the host cell.

### Claim 20

An isolated nucleic acid encoding an anti-NSP4 antibody comprising a heavy chain and a light chain, wherein the light chain comprises an HVR-L1 comprising the sequence of SEQ ID NO:19, an HVR-L2 comprising the sequence of SEQ ID NO:11, and an HVR-L3 comprising the sequence of SEQ ID NO:12; and wherein the heavy chain comprises an HVR-H1 comprising the sequence of SEQ ID NO:41, an HVR-H2 comprising the sequence of SEQ ID NO:42, and an HVR-H3 comprising the sequence of SEQ ID NO:43.

### Claim 21 (depends on 20)

A vector comprising the nucleic acid of claim 20.

### Claim 22 (depends on 20)

A host cell comprising the nucleic acid of claim 20.

### Claim 23 (depends on 22)

A method for producing an antibody comprising culturing the host cell of claim 22 under conditions suitable for production of the antibody.

### Claim 24 (depends on 23)

The method of claim 23, further comprising recovering the antibody produced by the host cell.

### Claim 25

An isolated nucleic acid encoding an anti-NSP4 antibody comprising a heavy chain and a light chain, wherein the light chain comprises an HVR-L1 comprising the sequence of SEQ ID NO:19, an HVR-L2 comprising the sequence of SEQ ID NO:11, and an HVR-L3 comprising the sequence of SEQ ID NO:12; and wherein the heavy chain comprises an HVR-H1 comprising the sequence of SEQ ID NO:53, an HVR-H2 comprising the sequence of SEQ ID NO:54, and an HVR-H3 comprising the sequence of SEQ ID NO:55.

### Claim 26 (depends on 25)

A vector comprising the nucleic acid of claim 25.

### Claim 27 (depends on 25)

A host cell comprising the nucleic acid of claim 25.

### Claim 28 (depends on 27)

A method for producing an antibody comprising culturing the host cell of claim 27 under conditions suitable for production of the antibody.

### Claim 29 (depends on 28)

The method of claim 28, further comprising recovering the antibody produced by the host cell.

### Claim 30

An isolated nucleic acid encoding an anti-NSP4 antibody comprising a heavy chain and a light chain, wherein the light chain comprises an HVR-L1 comprising the sequence of SEQ ID NO:19, an HVR-L2 comprising the sequence of SEQ ID NO:11, and an HVR-L3 comprising the sequence of SEQ ID NO:12; and wherein the heavy chain comprises an HVR-H1 comprising the sequence of SEQ ID NO:59, an HVR-H2 comprising the sequence of SEQ ID NO:60, and an HVR-H3 comprising the sequence of SEQ ID NO:61.

### Claim 31 (depends on 30)

A vector comprising the nucleic acid of claim 30.

### Claim 32 (depends on 30)

A host cell comprising the nucleic acid of claim 30.

### Claim 33 (depends on 32)

A method for producing an antibody comprising culturing the host cell of claim 32 under conditions suitable for production of the antibody.

### Claim 34 (depends on 33)

The method of claim 33, further comprising recovering the antibody produced by the host cell.
