Anti-integrin antibodies, compositions, methods and uses

• US 7,163,681 B2
• Filed: 11/24/2003
• Issued: 01/16/2007
• Est. Priority Date: 08/07/2000
• Status: Expired due to Term

• Current Assignee: Janssen Biotech, Inc. (Johnson & Johnson)
• Original Assignee: Centocor Incorporated (Johnson & Johnson)
• Inventors: Snyder, Linda, Giles-Komar, Jill, Trikha, Mohit, Nakada, Marian T.
• Primary Examiner(s): Haddad; Maher M.
• Application Number:
  US10/720,323
• Publication Number:
  US 20040185507A1
• Time in Patent Office: 1,149 Days
• Field of Search: 530/388.15, 530/388.22, 424/144.1
• US Class Current: 424/144.1
• CPC Class Codes: A01K 2217/05 Animals comprising random inserted nucleic acids (transgenic)
• CPC Class Codes: A01K 2267/01 Animal expressing industrially exogenous proteins
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 21/02 Muscle relaxants, e.g. for tetanus or cramps
• CPC Class Codes: A61P 23/00 Anaesthetics
• CPC Class Codes: A61P 23/02 Local anaesthetics
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/20 Hypnotics; Sedatives
• CPC Class Codes: A61P 25/24 Antidepressants
• 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 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/00 : Drugs for disorders of the endocrine system
• CPC Class Codes: A61P 5/04 : for decreasing, blocking or antagonising the activity of the hypothalamic hormones
• CPC Class Codes: A61P 5/44 : Glucocorticosteroids; Drugs increasing or potentiating the activity of glucocorticosteroids
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07K 16/2839 : against the integrin superfamily
• CPC Class Codes: C07K 16/2848 : against integrin beta3-subunit-containing molecules, e.g. CD41, CD51, CD61
• CPC Class Codes: C07K 16/4258 : against anti-receptor Ig
• CPC Class Codes: C07K 2317/21 : from primates, e.g. man
• CPC Class Codes: C07K 2317/565 : Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/76 : Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C07K 2317/92 : Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
• CPC Class Codes: G01N 2333/70546 : Integrin superfamily, e.g. VLAs, leuCAM, GPIIb/GPIIIa, LPAM
• CPC Class Codes: G01N 33/5008 : for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
• CPC Class Codes: G01N 33/5029 : on cell motility
• CPC Class Codes: G01N 33/68 : involving proteins, peptides or amino acids involving lipoproteins G01N33/92
• CPC Class Codes: Y02A 50/30 : Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The present invention relates to at least one novel anti-alpha-V subunit antibodies, including isolated nucleic acids that encode at least one anti-alpha-V subunit antibody, alpha-V subunit, vectors, host cells, transgenic animals or plants, and methods of making and using thereof, including therapeutic compositions, methods and devices.

Claims

1. An isolated human monoclonal antibody comprising human heavy chain and human light chain variable regions comprising the amino acid sequences shown in SEQ ID NO:

7 and SEQ ID NO;

8, respectively.

2. The antibody of claim 1 which completely inhibits M21 cell adhesion to vitronectin.

3. The antibody of claim 1, comprising a human IgG heavy chain and a human kappa light chain.

4. The antibody of claim 1, comprising an IgG1 or IgG3 heavy chain.

5. A pharmaceutical composition comprising the antibody of claim 1 and a pharmaceutically acceptable carrier.

6. A composition according to claim 5 wherein the antibody is combined with an anti-neoplastic agent selected from the group consisting of a radiopharmaceutical, an estrogen receptor modulator, a retinoid, a topoisomererase inhibitor, a cytotoxin, an alkylating agent, a nitrogen mustard, a nitrosourea , an antimetabolite, a mitotic inhibitor, and a radiosensitizer.

7. A composition according to claim 6 wherein the alkylating agent is dacarbazine.

8. An immunoconjugate comprising the antibody according to claim 1 linked to a therapeutic agent.

9. The immunoconjugate of claim 8 wherein the therapeutic agent is a cytotoxin.

10. The immunoconjugate of claim 9 wherein the therapeutic agent is a radioisotope.

11. A pharmaceutical composition comprising the immunoconjugate of claim 8 and a pharmaceutically acceptable carrier.

12. An article of manufacture for human pharmaceutical or diagnostic use, comprising packaging material and a container comprising a solution or a lyophilized form of isolated human anti-alpha-V subunit antibody according to claim 1.

13. The article of manufacture of claim 12, wherein said container is a component of a parenteral, subcutaneous, intramuscular, intravenous, intrarticular, intrabronchial, intraabdominal, intracapsular, intracartilaginous, intracavitary, intracelial, intracelebellar, intracerebroventricular, intracolic, intracervical, intragastric, intrahepatic, intramyocardial, intraosteal, intrapelvic, intrapericardiac, intraperitoneal, intrapleural, intraprostatic, intrapulmonary, intrarectal, intrarenal, intraretinal, intraspinal, intrasynovial, intrathoracic, intrauterine, intravesical, bolus, vaginal, rectal, buccal, sublingual, intranasal, or transdermal delivery device or system.

14. An isolated human monoclonal antibody according to claim 1 produced by a method comprising transfecting a host cell or transgenic animal or transgenic plant or plant cell capable of expressing in recoverable amounts said antibody with a nucleic acid molecule encoding said antibody and recovering the antibody from cell, animal or plant.

15. An isolated human monoclonal antibody according to claim 1, wherein said antibody binds purified human α

_vβ

₃ and α

_vβ

₅ integrins with an affinity of at least one selected from at least 10<sup>−

9</sup> M, at least 10<sup>−

10</sup> M, at least 10<sup>−

11</sup> M, or at least 10<sup>−

12</sup> M.

16. An isolated human monoclonal antibody according to claim 15, wherein said antibody binds purified human α

_vβ

₃ and α

_vβ

₅ integrins with an affinity of at least 10<sup>−

9</sup> M.

17. An isolated human monoclonal antibody according to claim 15, wherein said antibody binds purified human α

_vβ

₃ and α

_vβ

₅ integrins with an affinity of at least 10<sup>−

10</sup> M.

18. An isolated human monoclonal antibody according to claim 15, wherein said antibody binds purified human α

_vβ

₃ or α

_vβ

₅ integrins with an affinity of at least 10<sup>−

11</sup> M.

19. An isolated human monoclonal antibody according to claim 15, wherein said antibody binds human α

_vβ

₆ integrin in HEK-293 cells transfected with a cDNA construct to overexpress α

_vβ

₆ integrin.

20. The human monoclonal antibody of claim 1 which is an IgG1kappa antibody.