# US 9,518,128 B2 · Thrombin-binding antibody molecules > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 9,518,128 B2 - Document ID: US9518128B2 - Status: Granted - Kind: B2 - Application number: 14/309,403 - Filed: 2014-06-19 - Published: 2014-10-09 - Granted: 2016-12-13 - 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/US9518128B2 ## 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, comprising an LCDR1 having the amino acid sequence of SEQ ID NO: 15, an LCDR2 having the amino acid sequence of SEQ ID NO: 8, and an LCDR3 having the amino acid sequence of SEQ ID NO: 9, and comprising an HCDR1 having the amino acid sequence of SEQ ID NO: 3, an HCDR2 having the amino acid sequence of SEQ ID NO: 4, and an HCDR3 having the amino acid sequence of SEQ ID NO: 5. ### Claim 2 (depends on 1) The antibody molecule according to claim 1, wherein the antibody molecule comprises a variable heavy chain region (VH) having the amino acid sequence of SEQ ID NO: 2. ### Claim 3 (depends on 1) The antibody molecule according to claim 1, wherein the antibody molecule comprises a variable light chain region (VL) having the amino acid sequence of SEQ ID NO: 14. ### Claim 4 (depends on 1) A pharmaceutical composition, comprising the antibody molecule according to claim 1 and a pharmaceutically acceptable excipient or carrier. ### Claim 5 (depends on 1) The antibody molecule according to claim 1, wherein the antibody molecule is a Fab, diabody, triabody, tetrabody, or minibody. ### Claim 6 (depends on 1) The antibody molecule according to claim 1, wherein the antibody molecule is a monoclonal antibody. ### Claim 7 (depends on 6) The antibody molecule according to claim 6, wherein the monoclonal antibody comprises an IgG constant region. ### Claim 8 (depends on 7) The antibody molecule according to claim 7, wherein the IgG constant region is an IgG1 or IgG4 constant region. ### Claim 9 (depends on 1) The antibody molecule according to claim 1, wherein the antibody molecule is a human antibody. ### Claim 10 An isolated or recombinant antibody molecule that specifically binds to the exosite 1 region of thrombin, comprising a variable light chain region (VL) comprising the amino acid sequence of SEQ ID NO: 14 and a variable heavy chain region (VH) comprising an HCDR1 having the amino acid sequence of SEQ ID NO: 3, an HCDR2 having the amino acid sequence of SEQ ID NO: 4, and an HCDR3 having the amino acid sequence of SEQ ID NO: 5. ### Claim 11 (depends on 10) The antibody molecule according to claim 10, wherein the antibody molecule is a monoclonal antibody. ### Claim 12 (depends on 11) The antibody molecule according to claim 11, wherein the monoclonal antibody comprises an IgG constant region. ### Claim 13 (depends on 12) The antibody molecule according to claim 12, wherein the IgG constant region is an IgG1 or IgG4 constant region. ### Claim 14 (depends on 10) The antibody molecule according to claim 10, wherein the antibody molecule is a human antibody. ### Claim 15 (depends on 10) A pharmaceutical composition, comprising the antibody molecule according to claim 10 and a pharmaceutically acceptable excipient or carrier. ### Claim 16 An isolated or recombinant antibody molecule, comprising a variable light chain region (VL) comprising the amino acid sequence of SEQ ID NO: 14 and a variable heavy chain region (VH) comprising the amino acid sequence of SEQ ID NO: 2. ### Claim 17 (depends on 16) The antibody molecule according to claim 16, wherein the antibody molecule is a monoclonal antibody. ### Claim 18 (depends on 17) The antibody molecule according to claim 17, wherein the monoclonal antibody comprises an IgG constant region. ### Claim 19 (depends on 18) The antibody molecule according to claim 18, wherein the IgG constant region is an IgG1 or IgG4 constant region. ### Claim 20 (depends on 16) The antibody molecule according to claim 16, wherein the antibody molecule is a human antibody. ### Claim 21 (depends on 16) A pharmaceutical composition, comprising the antibody molecule according to claim 16 and a pharmaceutically acceptable excipient or carrier. ### Claim 22 An isolated or recombinant monoclonal antibody molecule, comprising a variable light chain region (VL) comprising the amino acid sequence of SEQ ID NO: 14, a variable heavy chain region (VH) comprising the amino acid sequence of SEQ ID NO: 2, and a human IgG constant region. ### Claim 23 (depends on 22) The antibody molecule according to claim 22, wherein the human IgG constant region is a human IgG1 constant region. ### Claim 24 (depends on 22) The antibody molecule according to claim 22, wherein the human IgG constant region is a human IgG4 constant region. ### Claim 25 (depends on 22) A pharmaceutical composition, comprising the antibody molecule according to claim 22 and a pharmaceutically acceptable excipient or carrier. ### Claim 26 (depends on 23) A pharmaceutical composition, comprising the antibody molecule according to claim 23 and a pharmaceutically acceptable excipient or carrier. ### Claim 27 (depends on 24) A pharmaceutical composition, comprising the antibody molecule according to claim 24 and a pharmaceutically acceptable excipient or carrier.