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 mammalian anti-IL-12 antibody or antibody fragment, comprising at least two complementarity determining regions (CDRs), wherein said antibody binds to a portion of the IL-12 protein corresponding to at least one amino acid residue selected from residues 1-88 of the amino acid sequence of SEQ ID NO:9. 
     
     
         2 . An isolated mammalian anti-IL-12 antibody or antibody fragment, comprising at least two complementarity determining regions (CDRs), wherein said antibody 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 SEQ ID NO:9. 
     
     
         3 . The anti-IL-12 antibody or antibody fragment according to  claim 2 , wherein said antibody or antibody fragment binds to a portion of the IL-12 protein corresponding to at least one amino acid residue selected from the group consisting of residues 23, 40, 43, 45, 59, and 62 of the amino acid sequence of SEQ ID NO:9. 
     
     
         4 . The anti-IL-12 antibody or antibody fragment according to  claim 3 , wherein said antibody or antibody fragment binds to a portion of the IL-12 protein corresponding to at least one amino acid residue selected from the group consisting of residues 45, 59, and 62 of the amino acid sequence of SEQ ID NO:9. 
     
     
         5 . The anti-IL-12 antibody or antibody fragment according to  claim 2 , wherein said antibody 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. 
     
     
         6 . The anti-IL-12 antibody according to  claim 2 , wherein said antibody or antibody fragment substantially neutralizes at least one activity of at least one IL-12 protein. 
     
     
         7 . An isolated nucleic acid molecule encoding the isolated mammalian anti-IL-12 antibody or antibody fragment of  claim 2 . 
     
     
         8 . An isolated nucleic acid vector comprising the isolated nucleic acid molecule according to  claim 7 . 
     
     
         9 . An isolated prokaryotic or eukaryotic host cell comprising the isolated nucleic acid molecule according to  claim 8 . 
     
     
         10 . The host cell according to  claim 9 , wherein said host cell is at least one selected from COS-1, COS-7, HEK293, BHK21, CHO, BSC-1, Hep G2, 653, SP2/0, 293, HeLa, myeloma, or lymphoma cells, or any derivative, immortalized or transformed cell thereof. 
     
     
         11 . A method for producing an anti-IL-12 antibody or antibody fragment, comprising translating the nucleic acid molecule according to  claim 7  under conditions in vitro, such that the IL-12 antibody or antibody fragment is expressed in detectable or recoverable amounts. 
     
     
         12 . A composition comprising the isolated mammalian anti-IL-12 antibody or antibody fragment according to  claim 2 , and at least one pharmaceutically acceptable carrier or diluent. 
     
     
         13 . The composition according to  claim 12 , 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 immunization, 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. 
     
     
         14 . An anti-idiotype antibody or fragment that specifically binds the isolated mammalian anti-IL-12 antibody or antibody fragment according to  claim 2 . 
     
     
         15 . A method for diagnosing or treating an IL-12 related condition in a cell, tissue, organ or animal, comprising
 contacting or administering a composition comprising an effective amount of the isolated mammalian anti-IL-12 antibody or antibody fragment according to  claim 2 , with, or to, said cell, tissue, organ or animal.   
     
     
         16 . The method according to  claim 15 , wherein said effective amount is 0.001-50 mg/kilogram of said cells, tissue, organ or animal. 
     
     
         17 . The method according to  claim 15 , wherein said contacting or 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, and transdermal. 
     
     
         18 . The method according to  claim 15 , further comprising administering, prior, concurrently or after said contacting or administering, 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 immunization, 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. 
     
     
         19 . The method according to  claim 15 , wherein said IL-12 related condition is psoriasis. 
     
     
         20 . The method according to  claim 15 , wherein said IL-12 related condition is psoriatic arthritis. 
     
     
         21 . The method according to  claim 15 , wherein said IL-12 related condition is Crohn's disease. 
     
     
         22 . The method according to  claim 15 , wherein said IL-12 related condition is lupus. 
     
     
         23 . A medical device, comprising an isolated mammalian anti-IL-12 antibody or antibody fragment according to  claim 2 , wherein said device is suitable to contacting or administering said anti-IL-12 antibody 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, and transdermal.