Anti-ngf antibodies and their use

Abstract

The present disclosure encompasses NGF binding proteins, specifically to antibodies that are chimeric, CDR grafted and caninized antibodies, and methods of making and uses thereof. The antibodies, or antibody portions, of the disclosure are useful for detecting NGF and for inhibiting NGF activity, e.g., in a mammal subject suffering from a disorder in which NGF activity is detrimental.

1 - 20 : (canceled) 
     
     
         21 . An isolated anti-NGF antibody that specifically binds to Nerve Growth Factor (NGF) and inhibits the binding of NGF to the TrkA receptor comprising:
 a) a variable heavy chain (VH) region comprising:
 i) a Complimentary Determining Region 1 (CDR1) comprising an amino acid sequence having at least about 90% sequence identity to the amino acid sequence comprising SEQ ID NO. 61, 
 ii) a Complimentary Determining Region 2 (CDR2) comprising an amino acid sequence having at least about 90% sequence identity to the amino acid sequence comprising SEQ ID NO. 62; and 
 iii) a Complimentary Determining Region 3 (CDR3) comprising an amino acid sequence having at least about 90% sequence identity to the amino acid sequence comprising SEQ ID NO. 63; and 
   b) a variable light chain (VL) region comprising:
 i) a Complimentary Determining Region 1 (CDR1) comprising an amino acid sequence having at least about 90% sequence identity to the amino acid sequence comprising SEQ ID NO. 64, 
 ii) a Complimentary Determining Region 2 (CDR2) comprising an amino acid sequence having at least about 90% sequence identity to the amino acid sequence comprising SEQ ID NO. 65; and 
 iii) a Complimentary Determining Region 3 (CDR3) comprising an amino acid sequence having at least about 90% sequence identity to the amino acid sequence comprising SEQ ID NO. 66; and 
   any variants thereof having one or more conservative amino acid substitutions in at least one of CDR1, CDR2 or CDR3 within any of the variable light or variable heavy chain regions of said antigen binding protein.   
     
     
         22 . The antibody of  claim 21  wherein said antibody is selected from the group consisting of: a monoclonal antibody; a chimeric antibody, a single chain antibody, a tetrameric antibody, a tetravalent antibody, a multispecific antibody, a domain-specific antibody, a domain-deleted antibody, a fusion protein, an ScFc fusion protein, an Fab fragment, an Fab′ fragment, an F(ab′) 2  fragment, an Fv fragment, an ScFv fragment, an Fd fragment, a single domain antibody, a dAb fragment, a small modular immunopharmaceutical (SMIP) a nanobody, and IgNAR molecule. 
     
     
         23 . The antibody of  claim 22  wherein said antibody comprises a monoclonal antibody. 
     
     
         24 . The antibody of  claim 23  wherein said antibody comprises a felinized antibody. 
     
     
         25 . The antibody of  claim 23  wherein said antibody comprises a chimeric antibody. 
     
     
         26 . A pharmaceutical composition comprising a therapeutically effective amount of the antibody of  claim 21  and a pharmaceutically acceptable carrier, diluent or excipient. 
     
     
         27 . A method of inhibiting NGF in a subject comprising administering a therapeutically effective amount of the composition of  claim 26 . 
     
     
         28 . The method of  claim 27  wherein the subject comprises a feline. 
     
     
         29 . A method of treating an NGF-related disorder comprising administering to a subject a therapeutically effective amount of the pharmaceutical composition of  claim 26 . 
     
     
         30 . The method of  claim 29  wherein the NGF-related disorder is selected from the group consisting of: cardiovascular diseases, atherosclerosis, obesity, type 2 diabetes, metabolic syndrome, pain and inflammation. 
     
     
         31 . The method of  claim 30  wherein the NGF-related disorder is a pain disorder. 
     
     
         32 . The method of  claim 31  wherein said NGF-related disorder is a pain disorder and is selected from the group consisting of: osteoarthritis pain, rheumatoid arthritis pain, surgical and postsurgical pain, incisional pain, general inflammatory pain, cancer pain, pain from trauma, neuropathic pain, neuralgia, diabetic neuropathy pain, pain associated with rheumatic diseases, pain associated with musculoskeletal diseases, visceral pain, and gastrointestinal pain. 
     
     
         33 . The method of  claim 32  wherein the pain disorder comprises osteoarthritis pain. 
     
     
         34 . The method of  claim 32  wherein the pain disorder comprises surgical and postsurgical pain. 
     
     
         35 . The method of  claim 32  wherein the pain disorder comprises cancer pain. 
     
     
         36 . The method of  claim 29  wherein the subject comprises a feline.