Anti-IL-12 Antibodies, Epitopes, Compositions, Methods and Uses

Abstract

An anti-IL-12 antibody or fragment thereof that binds to a portion of the IL-12 protein corresponding to at least one amino acid residue selected from the group consisting of residues 15, 17-21, 23, 40-43, 45-47, 54-56 and 58-62 of the amino acid sequence of the p40 subunit of IL-12, including isolated nucleic acids that encode at least one anti-IL-12 antibody or fragment thereof, vectors, host cells, transgenic animals or plants, and methods of making and using thereof have applications in diagnostic and/or therapeutic compositions, methods and devices.

What is claimed is: 
     
         1 . An isolated human anti-IL-12 antibody fragment, wherein said antibody fragment binds to a conformational epitope of the IL-12 protein comprising residues 15, 17-21, 23, 40-43, 45-47, 54-56 and 58-62 of the amino acid sequence of SEQ ID NO:9. 
     
     
         2 . The anti-IL-12 antibody fragment according to  claim 1 , wherein said antibody fragment binds to a conformational epitope of the IL-12 protein comprising residues 23, 40, 43, 45, 59, and 62 of the amino acid sequence of SEQ ID NO:9. 
     
     
         3 . The anti-IL-12 antibody fragment according to  claim 1 , wherein said antibody fragment binds IL-12 with an affinity of at least one selected from at least 10 −9 M, at least 10 −10  M, at least 10 −11  M, or at least 10 −12  M. 
     
     
         4 . The anti-IL-12 antibody fragment according to  claim 1 , wherein said antibody fragment substantially neutralizes at least one activity of at least one IL-12 protein comprising production of interferon gamma and IL-2 from CD4+ T cells. 
     
     
         5 . A composition comprising the isolated mammalian anti-IL-12 antibody fragment according to  claim 1 , and at least one pharmaceutically acceptable carrier or diluent. 
     
     
         6 . The composition according to  claim 5 , further comprising 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, 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 corticosteriod, an anabolic steroid, an erythropoietin, an immunoglobulin, an immunosuppressive, a growth hormone, a hormone replacement drug, a radiopharmaceutical, an antidepressant, an antipsychotic, a stimulant, an asthma medication, a beta agonist, an inhaled steroid, an epinephrine or analog, a cytokine, and a cytokine antagonist. 
     
     
         7 . An anti-idiotype antibody fragment that specifically binds the isolated anti-IL-12 antibody fragment according to  claim 1 . 
     
     
         8 . An isolated anti-IL-12 antibody fragment, wherein said antibody fragment binds to a conformational epitope of the p40 protein monomer or a p40 subunit in an IL-12 protein comprising residues 15, 17-21, 23, 40-43, 45-47, 54-56 and 58-62 of the amino acid sequence of SEQ ID NO:9. 
     
     
         9 . An isolated antibody fragment, wherein said antibody fragment competes for binding with the isolated antibody fragment of  claim 1 . 
     
     
         10 . An isolated antibody fragment, wherein said antibody fragment competes for binding with the isolated antibody fragment of  claim 2 . 
     
     
         11 . The isolated antibody fragment of  claim 1 , wherein said antibody fragment is selected from the group consisting of a Fab, Fab′, F(ab′) 2 , facb, pFc′, Fd, Fv and scFv.