Anti-integrin antibodies, compositions, methods and uses
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.
1. An isolated human anti-αV subunit antibody or antigen-binding fragment thereof, comprising a human heavy chain having CDR1, CDR2 and CDR3 regions comprising the amino acid sequences of SEQ ID NO:1, SEQ ID NO:2 and SEQ ID NO:3 respectively, and a human light chain having CDR1, CDR2 and CDR3 regions comprising the amino acid sequences of SEQ ID NO:4, SEQ ID NO:5 and SEQ ID NO:6 respectively.
2. The isolated antibody or antigen-binding fragment thereof of claim 1 , which binds to human αV integrin subunit with a Kd of 10 −8 M or less.
3. An isolated human monoclonal antibody or antigen-binding fragment thereof that competes for binding to human αV integrin subunit with the antibody of claim 1 .
4. The antibody or antigen-binding fragment thereof of claim 1 which completely inhibits M21 cell adhesion to vitronectin.
5. The antibody or antigen-binding fragment thereof of claim 1 , comprising a human IgG heavy chain and a human kappa light chain.
6. The antibody or antigen-binding fragment thereof of claim 1 , comprising an IgG1 or IgG3 heavy chain.
7. A pharmaceutical composition comprising the antibody or antigen-binding fragment thereof of claim 1 and a pharmaceutically acceptable carrier.
8. A composition according to claim 7 , further 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 anesthetic, a neuromuscular blocker, an antimicrobial, an antipsoriatic, a corticosteroid, an anabolic steroid, an erythropoietin, 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.
9. A composition according to claim 7 , wherein the antibody or antigen-binding fragment thereof 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.
10. A composition according to claim 9 , wherein the anti-neoplastic agent is dacarbazine.
11. An immunoconjugate comprising the antibody or antigen-binding fragment thereof of claim 1 linked to a therapeutic agent.
12. The immunoconjugate of claim 11 wherein the therapeutic agent is a cytotoxin.
13. The immunoconjugate of claim 11 wherein the therapeutic agent is a radioisotope.
14. A pharmaceutical composition comprising the immunoconjugate of any one of claims 11 - 13 and a pharmaceutically acceptable carrier.
15. An article of manufacture for human pharmaceutical or diagnostic use, comprising packaging material and a container comprising a solution or a lyophilized form of at least one isolated human anti-αV subunit antibody according to claim 1 .
16. The article of manufacture of claim 15 , 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.
17. The antibody or antigen-binding fragment of claim 1 , which is of immunoglobulin class IgG1, IgG2, IgG3, IgG4 IgA, IgD IgE or IgM.
18. The antigen-binding fragment of claim 1 selected from the group consisting of Fab, Fab′, F(ab′) 2 and Fv.
19. The human anti-αV subunit antibody or antigen-binding fragment thereof of claim 1 , which is produced recombinantly.
20. The human anti-αV subunit antibody or antigen-binding fragment thereof of claim 1 , which is produced by chemical synthesis.
21. The human anti-αV subunit antibody or antigen-binding fragment thereof of claim 1 , which is produced by using a hybridoma.