# US 10,370,454 B2 · Thrombin-binding antibody molecules and uses thereof

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 10,370,454 B2
- Document ID: US10370454B2
- Status: Granted
- Kind: B2
- Application number: 15/976,595
- Filed: 2018-05-10
- Published: 2018-11-22
- Granted: 2019-08-06
- Earliest claimed: 2011-12-14
- Assignees: Janssen Pharmaceuticals, Inc.
- Applicants: Janssen Pharmaceuticals, Inc.
- Inventors: James Andrew Huntington; Trevor Baglin; Jonathan Langdown
- Web page: https://patentgrep.com/patent/US10370454B2

## CPC

- C07K 16/40: against enzymes
- C07K 16/36: against blood coagulation factors
- A61K 2039/505: {comprising antibodies}
- C07K 2317/14: Specific host cells or culture conditions, e.g. components, pH or temperature
- C07K 2317/21: from primates, e.g. man
- C07K 2317/34: Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
- C07K 2317/41: Glycosylation, sialylation, or fucosylation
- C07K 2317/52: Constant or Fc region; Isotype
- C07K 2317/55: Fab or Fab'
- C07K 2317/56: variable (Fv) region, i.e. VH and/or VL
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/626: Diabody or triabody
- 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)

## Abstract

This invention relates to isolated antibodies which recognize the exosite 1 epitope of thrombin and selectively inhibit thrombin without promoting bleeding. These antibody molecules may be useful in the treatment and prevention of thrombosis, embolism and other conditions mediated by thrombin.

## Claims

### Claim 1

An isolated or recombinant antibody molecule that specifically binds to the exosite 1 region of thrombin, wherein the antibody molecule inhibits thrombosis or embolism but does not promote bleeding, and wherein the antibody molecule binds amino acids Q38, R73, T74, and Y76 relative to the amino acid sequence of SEQ ID NO: 1, the antibody molecule comprising a variable heavy domain, a variable light domain, and an IgG constant region, wherein the variable heavy domain comprises a heavy chain complementarity determining region 3 (HCDR3) having the amino acid sequence of SEQ ID NO:5, a HCDR2 having the amino acid sequence of SEQ ID NO: 4, and a HCDR1 having the amino acid sequence of SEQ ID NO: 3, a variable light domain comprising a light chain complementarity determining region 1 (LCDR1) having the amino acid sequence of SEQ ID NO: 15, a LCDR2 having the amino acid sequence of SEQ ID NO: 8, and a LCDR3 having the amino acid sequence of SEQ ID NO: 9.

### Claim 2 (depends on 1)

The antibody molecule of claim 1, wherein the antibody molecule further binds one or more amino acids selected from the group consisting of: M32, F34, S36a, P37, E39, L40, L65, R67, R75, R77a, I82 and Q151 relative to the amino acid sequence of SEQ ID NO: 1.

### Claim 3 (depends on 1)

The antibody molecule of claim 1, wherein the antibody molecule further binds R77a relative to the amino acid sequence of SEQ ID NO: 1.

### Claim 4 (depends on 1)

A pharmaceutical composition comprising the antibody molecule according to claim 1 and a pharmaceutically acceptable carrier or excipient.

### Claim 5 (depends on 1)

The antibody molecule of claim 1 wherein the IgG constant region is an IgG1 constant region or an IgG4 constant region.