Anti-Prokineticin Receptor (PROKR) Antibodies and Uses Thereof

Abstract

The present invention provides antibodies that bind to prokineticin receptors (PROKRs) and methods of using same. According to certain embodiments of the invention, the antibodies are fully human antibodies that bind to human PROKR1 and/or PROKR2. The present invention includes antibodies that bind cell surface-expressed PROKR1 and/or PROKR2. In certain embodiments, the antibodies of the present invention are capable of blocking prokineticin (PK)-mediated activation of one or more PROKR. The antibodies of the invention are useful for the treatment of various diseases and disorders mediated by prokineticin signaling.

What is claimed is: 
     
         1 . A method for treating or attenuating pain, the method comprising administering to a subject in need thereof a composition comprising an isolated antibody or antigen-binding fragment thereof that specifically binds cell surface-expressed prokineticin receptor 1 (PROKR1) and/or cell surface-expressed prokineticin receptor 2 (PROKR2), wherein the antibody or antigen-binding fragment comprises HCDR1-HCDR2-HCDR3-LCDR1-LCDR2-LCDR3 domains defined by SEQ ID NOs: 20-22-24-28-30-32. 
     
     
         2 . The method of  claim 1 , wherein the antibody or antigen-binding fragment comprises: (a) a heavy chain variable region (HCVR) comprising the amino acid sequence set forth in SEQ ID NO: 18; and (b) a light chain variable region (LCVR) comprising the amino acid sequence set forth in SEQ ID NO: 26. 
     
     
         3 . The method of  claim 1 , wherein the pain is nociceptive pain, visceral pain, or inflammatory pain. 
     
     
         4 . The method of  claim 1 , wherein the pain is associated with a condition selected from the group consisting of inflammation, post-operative incision, neuropathy, bone fracture, burn, osteoporotic fracture, bone cancer, gout, migraine headache, and fibromyalgia. 
     
     
         5 . The method of  claim 1 , wherein the pain is cancer-associated pain. 
     
     
         6 . The method of  claim 1 , wherein the composition comprises a pharmaceutically acceptable carrier or diluent. 
     
     
         7 . The method of  claim 1 , wherein the subject is administered one or more additional therapeutic agents. 
     
     
         8 . The method of  claim 7 , wherein the additional therapeutic agent is selected from the group consisting of an antiviral, an antibiotic, an analgesic, a corticosteroid, an opioid, and an NSAID (non-steroidal anti-inflammatory drug). 
     
     
         9 . The method of  claim 7 , wherein the additional therapeutic agent is selected from the group consisting of: an anti-NGF antibody, an anti-PAR2 antibody, an anti-ASIC1 antibody, an anti-ASIC2 antibody, an anti-ASIC3 antibody, an anti-ASIC4 antibody, an anti-GFR alpha antibody, an anti-EGFR antibody, an anti-ErbB2 antibody, anti-ErbB3 antibody, an anti-ErbB4 antibody, an anti-EGFRvIII antibody, an anti-cMET antibody, an anti-IGF1R antibody, an anti-PDGFR-alpha antibody, an anti-PDGFR-beta antibody, a VEGF-Trap, an anti-VEGF antibody, an anti-DLL4 antibody, an anti-Ang2 antibody, an anti-FOLH1 antibody, an anti-PRLR antibody, an anti-STEAP1 antibody, an anti-STEAP2 antibody, an anti-TMPRSS2 antibody, an anti-MSLN antibody, an anti-CA9 antibody, an anti-uroplakin antibody, an anti-CD20 antibody, an anti-IL-1 antibody, an anti-IL-2 antibody, an anti-IL-3 antibody, an anti-IL-4 antibody, an anti-IL-5 antibody, an anti-IL-6 antibody, an anti-IL-8 antibody, an anti-IL-9 antibody, an anti-IL-11 antibody, an anti-IL-12 antibody, an anti-IL-13 antibody, an anti-IL-17 antibody, an anti-IL-18 antibody, an anti-IgE antibody, and an anti-TNF antibody. 
     
     
         10 . The method of  claim 1  wherein the antibody or antigen-binding fragment is an antibody. 
     
     
         11 . The method of  claim 10  wherein the antibody is an IgG1 antibody. 
     
     
         12 . The method of  claim 10  wherein the antibody is an IgG4 antibody. 
     
     
         13 . The method of  claim 10  wherein the antibody is administered to the subject by infusion or bolus injection.