Anti-integrin antibodies, compositions, methods and uses

• US 7,550,142 B2
• Filed: 11/13/2006
• Issued: 06/23/2009
• 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:
  US11/598,411
• Publication Number:
  US 20070128203A1
• Time in Patent Office: 953 Days
• Field of Search: None
• US Class Current: 424/133.1
• 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. A method of inhibiting growth of a cell expressing alpha v integrin subunit, comprising contacting the cell with an effective amount of 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, such that the growth of the cell is inhibited.

2. A method according to claim 1, wherein said effective amount is 0.001-50 mg/kilogram of said antibody.

9. The method of claim 1, wherein the human antibody is conjugated to or formulated with a therapeutic agent.

10. The method of claim 9 wherein the therapeutic agent is a cytotoxin.

11. A method according to claim 1 or 3, wherein said administrating is by at least one mode selected from 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.

12. A method according to claim 1 or 3, further comprising administering, prior, concurrently or after said antibody, at least one composition comprising an effective amount of at least one compound or protein selected from at least one of a detectable label or reporter, an anti-neoplastic agent, a TNF antagonist, an antirheumatic, a muscle relaxant, a narcotic, a non-steroid anti-inflammatory drug (NSAID), an analgesic, an anesthetic, a sedative, a local ansethetic, a neuromuscular blocker, an antimicrobial, an antipsoriatic, a corticosteriod, an anabolic steroid, an erythropoietin, an immunization, an immunoglobulin, an immunosuppressive, a growth hormone, a hormone antagonist, a reproductive hormone antagonist, a hormone release modulator, a hormone replacement drug, an antidepressant, an antipsychotic, a stimulant, an asthma medication, a beta agonist, an inhaled steroid, an epinephrine or analog, a cytokine, or a cytokine antagonist.

13. A method according to claim 12 wherein the antibody is combined with an anti-neoplastic agent selected from 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.

14. A method according to claim 13 wherein the anti-neoplastic agent is dacarbazine.

3. A method of treating a disease characterized by growth or metastasis of tumor cells, in a subject comprising administering to a subject an effective amount of 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, in an amount effective to treat the disease.

4. The method of claim 3, wherein the disease is cancer.

5. The method of claim 4, wherein the cancer is selected from the group consisting of—

melanoma, colon cancer, prostate cancer, breast cancer and renal carcinoma.

7. The method of claim 4, 5, or 6 wherein the antibody is administered in combination concurrently or sequentially with a cytotoxic agent.

8. The method of claim 7 wherein the cytotoxic agent Is dacarbazine.

6. The method of 4, wherein the cancer is metastatic melanoma.