FcγRIIB-specific antibodies and methods of use thereof

• US 7,425,620 B2
• Filed: 08/14/2003
• Issued: 09/16/2008
• Est. Priority Date: 08/14/2002
• Status: Active Grant

• Current Assignee: MacroGenics, Inc.
• Original Assignee: MacroGenics, Inc.
• Inventors: Koenig, Scott, Veri, Maria Concetta
• Primary Examiner(s): Haddad; Maher M.
• Assistant Examiner(s): DAHLE, CHUN WU
• Application Number:
  US10/643,857
• Publication Number:
  US 20040185045A1
• Time in Patent Office: 1,860 Days
• Field of Search: None
• US Class Current: 530/387.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/16 Otologicals
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: C07K 16/283 against Fc-receptors, e.g. CD16, CD32, CD64 CD23 C07K16/2851
• CPC Class Codes: C07K 16/2896 against molecules with a "CD"-designation, not provided for elsewhere
• CPC Class Codes: C07K 16/32 against translation products of oncogenes
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/34 Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
• CPC Class Codes: C07K 2317/732 Antibody-dependent cellular cytotoxicity [ADCC]

Abstract

The present invention relates to antibodies or fragments thereof that specifically bind FcγRIIB, particularly human FcγRIIB, with greater affinity than said antibodies or fragments thereof bind FcγRIIA, particularly human FcγRIIA. The invention provides methods of enhancing the therapeutic effect of therapeutic antibodies by administering the antibodies of the invention to enhance the effector function of the therapeutic antibodies. The invention also provides methods of enhancing efficacy of a vaccine composition by administering the antibodies of the invention.

Claims

1. A mouse monoclonal antibody produced by a clone selected from the group consisting of clone 1D5 having ATCC accession no. PTA-5958, clone 2E1 having ATCC accession no. PTA-5961, clone 2H9 having ATCC accession no. PTA-5962, clone 2D11 having ATCC accession no. PTA-5960, and clone 1F2 having ATCC accession no. PTA-5959.

2. An antibody which is a chimeric or humanized version of the mouse monoclonal antibody produced by a clone selected from the group consisting of clone 1D5 having ATCC accession no. PTA-5958, clone 2E1 having ATCC accession no. PTA-5961, clone 2H9 having ATCC accession no. PTA-5962, clone 2D11 having ATCC accession no. PTA-5960, and clone 1F2 having ATCC accession no. PTA-5959, or antigen-binding fragment thereof.

3. The antibody of claim 2 which is a F(ab′

)₂ fragment.

4. The antibody of claim 2 which is a F(ab′

) fragment.

5. The antibody of claim 2 which is conjugated to a therapeutic agent.

6. The antibody of claim 5, wherein the therapeutic agent is a cytotoxin.

7. The antibody of claim 6 wherein said cytotoxin is paclitaxel, cytochalasin B, gramicidin D, ethidium bromide, emetine, mitomycin, etoposide, tenoposide, vincristine, vinblastine, colchicin, doxorubicin, daunorubicin, dihydroxy anthracin dione, mitoxantrone, mithramycin, actinomycin D, 1-dehydrotestosterone, a glucocorticoids, procaine, tetracaine, lidocaine, propranolol, puromycin, epirubicin, or cyclophosphamide.

8. The antibody of claim 2 comprising at least one modification in the Fc region.

14. The antibody of claim 2, wherein said antibody is a chimeric version, or antigen-binding fragment thereof.

15. The antibody of claim 2, wherein said antibody is a humanized version, or antigen-binding fragment thereof.

9. A pharmaceutical composition comprising (i) a therapeutically effective amount of an antibody which is a chimeric or humanized version of the mouse monoclonal antibody produced by a clone selected from the group consisting of clone 1D5 having ATCC accession no. PTA-5958, clone 2E1 having ATCC accession no. PTA-5961, clone 2H9 having ATCC accession no. PTA-5962, clone 2D11 having ATCC accession no. PTA-5960, and clone 1F2 having ATCC accession no. PTA-5959, or an antigen-binding fragment thereof, and (ii) a pharmaceutically acceptable carrier.

10. The pharmaceutical composition of claim 9, wherein said antibody is a chimeric version, or antigen-binding fragment thereof.

11. The pharmaceutical composition of claim 9, wherein said antibody is a humanized version, or antigen-binding fragment thereof.

12. The pharmaceutical composition of claim 9, wherein said antibody is a F(ab′

)₂ fragment.

13. The pharmaceutical composition of claim 9, wherein said antibody is a F(ab′

) fragment.