Oncostatin m receptor antigen binding proteins

Abstract

The invention provides anti-oncostatin M receptor-β (OSMR) antigen binding proteins, e.g., antibodies and functional fragments, derivatives, muteins, and variants thereof. OSMR antigen binding proteins interfere with binding of OSM and/or IL-31 to OSMR. In some embodiments, anti-OSMR antigen binding proteins are useful tools in studying diseases and disorders associated with OSMR and are particularly useful in methods of treating diseases and disorders associated with OSMR and binding of OSM and/or IL-31 to OSMR.

1 . An oncostatin M receptor (OSMR) antigen binding protein comprising:
 a) a light chain variable domain having at least 90% identity to the amino acid sequence set forth in SEQ ID NO:27, SEQ ID NO:28, or SEQ ID NO:29;   b) a heavy chain variable domain having at least 90% identity to the amino acid sequence set forth in SEQ ID NO:9, SEQ ID NO:10, or SEQ ID NO:11; or   c) a light chain variable domain of a) and a heavy chain variable domain of b).   
     
     
         2 - 3 . (canceled) 
     
     
         4 . An oncostatin M receptor (OSMR) antigen binding protein, comprising:
 a) a light chain variable domain having no more than ten amino acid additions, deletions or substitutions from the amino acid sequence set forth in SEQ ID NO:27, SEQ ID NO:28, or SEQ ID NO:29;   b) a heavy chain variable domain having no more than ten amino acid additions, deletions or substitutions from the amino acid sequence set forth in SEQ ID NO:9, SEQ ID NO:10, or SEQ ID NO:11; or   c) the light chain variable domain of a) and the heavy chain variable domain of b).   
     
     
         5 - 8 . (canceled) 
     
     
         9 . An oncostatin M receptor (OSMR) antigen binding protein comprising:
 a light chain variable domain comprising:
 a) an LCDR1 having no more than three amino acid additions, deletions, or substitutions from the LCDR1 sequence set forth in SEQ ID NO:30; an LCDR2 having no more than three amino acid additions, deletions, or substitutions from the LCDR2 sequence set forth in SEQ ID NO:33; and an LCDR3 having no more than three amino acid additions, deletions, or substitutions from the LCDR3 sequence set forth in SEQ ID NO:36; 
 b) an LCDR1 having no more than three amino acid additions, deletions, or substitutions from the LCDR1 sequence set forth in SEQ ID NO:31; an LCDR2 having no more than three amino acid additions, deletions, or substitutions from the LCDR2 sequence set forth in SEQ ID NO:34; and an LCDR3 having no more than three amino acid additions, deletions, or substitutions from the LCDR3 sequence set forth in SEQ ID NO:37; or 
 c) an LCDR1 having no more than three amino acid additions, deletions, or substitutions from the LCDR1 sequence set forth in SEQ ID NO:32; an LCDR2 having no more than three amino acid additions, deletions, or substitutions from the LCDR2 sequence set forth in SEQ ID NO:35; and an LCDR3 having no more than three amino acid additions, deletions, or substitutions from the LCDR3 sequence set forth in SEQ ID NO:38; and 
   a heavy chain variable domain comprising:
 d) an HCDR1 having no more than three amino acid additions, deletions, or substitutions from the HCDR1 sequence set forth in SEQ ID NO:12; an HCDR2 having no more than three amino acid additions, deletions, or substitutions from the HCDR2 sequence set forth in SEQ ID NO:15; and an HCDR3 having no more than three amino acid additions, deletions, or substitutions from the HCDR3 sequence set forth in SEQ ID NO:18; 
 e) an HCDR1 having no more than three amino acid additions, deletions, or substitutions from the HCDR1 sequence set forth in SEQ ID NO:13; an HCDR2 having no more than three amino acid additions, deletions, or substitutions from the HCDR2 sequence set forth in SEQ ID NO:16; and an HCDR3 having no more than three amino acid additions, deletions, or substitutions from the HCDR3 sequence set forth in SEQ ID NO:19; or 
 f) an HCDR1 having no more than three amino acid additions, deletions, or substitutions from the HCDR1 sequence set forth in SEQ ID NO:14; an HCDR2 having no more than three amino acid additions, deletions, or substitutions from the HCDR2 sequence set forth in SEQ ID NO:17; and an HCDR3 having no more than three amino acid additions, deletions, or substitutions from the HCDR3 sequence set forth in SEQ ID NO:20. 
   
     
     
         10 - 32 . (canceled) 
     
     
         33 . An isolated nucleic acid encoding a polypeptide, said polypeptide comprising:
 a) a light chain variable domain having at least 95% identity to the amino acid sequence set forth in SEQ ID NO:27, SEQ ID NO:28, or SEQ ID NO:29;   b) a heavy chain variable domain having at least 95% identity to the amino acid sequence set forth in SEQ ID NO:9, SEQ ID NO:10, or SEQ ID NO:11;   c) a light chain variable domain having no more than five amino acid additions, deletions or substitutions from the amino acid sequence set forth in SEQ ID NO:27, SEQ ID NO:28, or SEQ ID NO:29;   d) a heavy chain variable domain having no more than five amino acid additions, deletions or substitutions from the amino acid sequence set forth in SEQ ID NO:9, SEQ ID NO:10, or SEQ ID NO:11;   e) a light chain variable domain comprising:
 i) an LCDR1 having no more than three amino acid additions, deletions, or substitutions from the LCDR1 sequence set forth in SEQ ID NO:30; an LCDR2 having no more than three amino acid additions, deletions, or substitutions from the LCDR2 sequence set forth in SEQ ID NO:33; and an LCDR3 having no more than three amino acid additions, deletions, or substitutions from the LCDR3 sequence set forth in SEQ ID NO:36; 
 ii) an LCDR1 having no more than three amino acid additions, deletions, or substitutions from the LCDR1 sequence set forth in SEQ ID NO:31; an LCDR2 having no more than three amino acid additions, deletions, or substitutions from the LCDR2 sequence set forth in SEQ ID NO:34; and an LCDR3 having no more than three amino acid additions, deletions, or substitutions from the LCDR3 sequence set forth in SEQ ID NO:37; or 
 iii) an LCDR1 having no more than three amino acid additions, deletions, or substitutions from the LCDR1 sequence set forth in SEQ ID NO:32; an LCDR2 having no more than three amino acid additions, deletions, or substitutions from the LCDR2 sequence set forth in SEQ ID NO:35; and an LCDR3 having no more than three amino acid additions, deletions, or substitutions from the LCDR3 sequence set forth in SEQ ID NO:38; or 
   f) a heavy chain variable domain comprising:
 i) an HCDR1 having no more than three amino acid additions, deletions, or substitutions from the HCDR1 sequence set forth in SEQ ID NO:12; an HCDR2 having no more than three amino acid additions, deletions, or substitutions from the HCDR2 sequence set forth in SEQ ID NO:15; and an HCDR3 having no more than three amino acid additions, deletions, or substitutions from the HCDR3 sequence set forth in SEQ ID NO:18; 
 ii) an HCDR1 having no more than three amino acid additions, deletions, or substitutions from the HCDR1 sequence set forth in SEQ ID NO:13; an HCDR2 having no more than three amino acid additions, deletions, or substitutions from the HCDR2 sequence set forth in SEQ ID NO:16; and an HCDR3 having no more than three amino acid additions, deletions, or substitutions from the HCDR3 sequence set forth in SEQ ID NO:19; or 
 iii) an HCDR1 having no more than three amino acid additions, deletions, or substitutions from the HCDR1 sequence set forth in SEQ ID NO:14; an HCDR2 having no more than three amino acid additions, deletions, or substitutions from the HCDR2 sequence set forth in SEQ ID NO:17; and an HCDR3 having no more than three amino acid additions, deletions, or substitutions from the HCDR3 sequence set forth in SEQ ID NO:20. 
   
     
     
         34 - 46 . (canceled) 
     
     
         47 . An expression vector comprising the isolated nucleic acid of  claim 33 . 
     
     
         48 - 50 . (canceled) 
     
     
         51 . A recombinant host cell comprising an isolated nucleic acid of  claim 33  operably linked to a promoter. 
     
     
         52 - 56 . (canceled) 
     
     
         57 . A method of treating a disease or disorder, said method comprising administering a therapeutically effective amount of an OSMR antigen binding protein of  claim 1  to a patient in need thereof. 
     
     
         58 . The method of  claim 57 , wherein the OSMR antigen binding protein is an antibody. 
     
     
         59 - 69 . (canceled) 
     
     
         70 . The method of  claim 57 , wherein the antigen binding protein inhibits binding of OSM and/or IL-31 to OSMR. 
     
     
         71 . The method of  claim 70 , wherein the disease or disorder is an autoimmune disorder, an inflammatory disorder, or a disorder associated with extracellular matrix deposition or remodeling. 
     
     
         72 . The method of  claim 71 , wherein the autoimmune disorder, the inflammatory disorder, or the disorder associated with extracellular matrix deposition or remodeling is fibrosis, cartilage degradation, arthritis, rheumatoid arthritis, scleroderma, scleroderma-associated interstitial lung disease, idiopathic pulmonary fibrosis, cirrhosis, psoriasis, atopic dermatitis, systemic cutaneous amyloidosis, primary cutaneous amyloidosis, inflammation, pruritic inflammation, prurigo nodularis, and pain. 
     
     
         73 . A method of making an oncostatin M receptor (OSMR) antigen binding protein, the method comprising:
 a) culturing a recombinant host cell of  claim 51 ; and   b) isolating the OSMR antigen binding protein from said culture.   
     
     
         74 . An oncostatin M receptor (OSMR) antigen binding protein of  claim 1 , wherein the OSMR antigen binding protein cross-competes with an antibody selected from the group consisting of:
 a) an antibody comprising a light chain comprising the amino acid sequence set forth in SEQ ID:24 and a heavy chain comprising the amino acid sequence set forth in SEQ ID NO:6;   b) an antibody comprising a light chain comprising the amino acid sequence set forth in SEQ ID:25 and a heavy chain comprising the amino acid sequence set forth in SEQ ID NO:7; and   c) an antibody comprising a light chain comprising the amino acid sequence set forth in SEQ ID:26 and a heavy chain comprising the amino acid sequence set forth in SEQ ID NO:8.   
     
     
         75 . An anti-oncostatin M receptor (OSMR) monoclonal antibody, wherein the anti-OSMR antibody competes with an anti-OSMR antibody defined by a light chain variable domain of SEQ ID NO:28 and a heavy chain variable domain of SEQ ID NO:54. 
     
     
         76 . A method of treating purigo nodularis, said method comprising systemically injecting a therapeutically effective amount of an anti-oncostatin M receptor (OSMR) monoclonal antibody to a human patient in need thereof,
 wherein systemically injecting the anti-OSMR antibody results in a decrease in severity of purigo nodularis, and
 wherein the anti-OSMR antibody competes with an anti-OSMR antibody defined by a light chain variable domain of SEQ ID NO:28 and a heavy chain variable domain of SEQ ID NO:54. 
   
     
     
         77 . The method of  claim 76 , wherein the anti-OSMR antibody is injected intravenously. 
     
     
         78 . The method of  claim 76 , wherein the anti-OSMR antibody is injected subcutaneously. 
     
     
         79 . The method of  claim 76 , wherein the anti-OSMR antibody comprises
 a light chain variable domain comprising a light chain complementary-determining region 1 (LCDR1) defined by SEQ ID NO:31, a light chain complementary-determining region 2 (LCDR2) defined by SEQ ID NO:34, and a light chain complementary-determining region 3 (LCDR3) defined by SEQ ID NO:37; and   a heavy chain variable domain comprising a heavy chain complementary-determining region 1 (HCDR1) defined by SEQ ID NO:13, a heavy chain complementary-determining region 2 (HCDR2) defined by SEQ ID NO:16, and a heavy chain complementary-determining region 3 (HCDR3) defined by SEQ ID NO:19.   
     
     
         80 . The method of  claim 76 , wherein the therapeutically effective amount ranges from 1 μg/kg to 20 mg/kg. 
     
     
         81 . The method of  claim 76 , wherein the therapeutically effective amount ranges from 10 μg/kg to 10 mg/kg. 
     
     
         82 . The method of  claim 76 , wherein the anti-OSMR antibody is a humanized antibody. 
     
     
         83 . The method of  claim 76 , wherein the anti-OSMR antibody is a human antibody. 
     
     
         84 . The method of  claim 76 , wherein the anti-OSMR antibody is a chimeric antibody. 
     
     
         85 . The method of  claim 76 , wherein the anti-OSMR antibody inhibits both OSM and IL-31 signaling. 
     
     
         86 . The method of  claim 76 , wherein the anti-OSMR antibody is an IgG1, IgG2, IgG4, or a hybrid antibody thereof. 
     
     
         87 . The method of  claim 76 , wherein the anti-OSMR antibody is aglycosylated.