Recombinant il-9 antibodies and uses thereof

Abstract

The present invention provides novel antibodies that immunospecifically bind to an IL-9 polypeptide and compositions comprising said antibodies. The present invention also provides methods and compositions preventing, treating, managing, and/or ameliorating diseases and disorders associated with aberrant expression and/or activity of IL 9 or IL-9 receptor or subunits thereof, autoimmune diseases, inflammatory diseases, proliferative diseases, and infections comprising administration of one or more antibodies thereof that immunospecifically bind to an IL-9 polypeptide. The invention also encompasses methods and compositions for diagnosing, monitoring, and prognosing these disorders. The present invention further relates to articles of manufacture and kits comprising antibodies that immunospecifically bind to an IL-9 polypeptide.

1 . An IL-9 antibody comprising a variable heavy (VH) domain having an amino acid sequence of the VH domain of 4D4, 4D4H2-1 D11, 4D4com-XF9, 4D4com-2F9, 7F3, 71A10, 22D3, 7F3com-2H2, 7F3com-3H5, or 7F3com-3D4, wherein the said antibody immunospecifically binds to a human IL-9 polypeptide. 
     
     
         2 . An IL-9 antibody comprising a variable light (VL) domain having an amino acid sequence of the VL domain of 4D4, 4D4H2-1 D11, 4D4com-XF9, 4D4com-2F9, 7F3, 71A10, 22D3, 7F3com-2H2, 7F3com-3H5, or 7F3com-3D4, wherein the said antibody immunospecifically binds to a human IL-9 polypeptide. 
     
     
         3 . The IL-9 antibody of  claim 1  further comprising a VL domain having an amino acid sequence of the VL domain of 4D4, 4D4H2-1 D11, 4D4com-XF9, 4D4com-2F9, 7F3, 71A10, 22D3, 7F3com-2H2, 7F3com-3H5, or 7F3com-3D4. 
     
     
         4 - 13 . (canceled) 
     
     
         14 . An IL-9 antibody comprising a VH CDR1, VH CDR2 and a VH CDR3 having the amino acid sequence of a VH CDR1, VH CDR2 and VH CDR3 of any one of:
 4D4, 4D4H2-1 D11, 4D4com-XF9, 4D4com-2F9, 7F3, 71A10, 22D3, 7F3com-2H2, 7F3com-3H5, or 7F3com-3D4.   
     
     
         15 - 27 . (canceled) 
     
     
         28 . An IL-9 antibody comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of a VL CDR1, VL CDR2, and VL CDR3 of any one of:
 4D4, 4D4H2-1 D11, 4D4com-XF9, 4D4com-2F9, 7F3, 71A10, 22D3, 7F3com-2H2, 7F3com-3H5, or 7F3com-3D4.   
     
     
         29 . The IL-9 antibody of  claim 14 , wherein the antibody further comprises a VL CDR1 having the amino acid sequence of a VL CDR1 of 4D4, 4D4H2-1 D11, 4D4com-XF9, 4D4com-2F9, 7F3, 71A10, 22D3, 7F3com-2H2, 7F3com-3H5, or 7F3com-3D4. 
     
     
         30 . The IL-9 antibody of  claim 14 , wherein the antibody further comprises a VL CDR2 having the amino acid sequence of a VL CDR2 of 4D4, 4D4H2-1 D11, 4D4com-XF9, 4D4com-2F9, 7F3, 71A10, 22D3, 7F3com-2H2, 7F3com-3H5, or 7F3com-3D4. 
     
     
         31 . The IL-9 antibody of  claim 14 , wherein the antibody further comprises a VL CDR3 having the amino acid sequence of a VL CDR3 of 4D4, 4D4H2-1 D11, 4D4com-XF9, 4D4com-2F9, 7F3, 71A10, 22D3, 7F3com-2H2, 7F3com-3H5, or 7F3com-3D4. 
     
     
         32 . The IL-9 antibody of  claim 29 , wherein the antibody further comprises a VL CDR2 having the amino acid sequence of a VL CDR2 of 4D4, 4D4H2-1 D11, 4D4com-XF9, 4D4com-2F9, 7F3, 71A10, 22D3, 7F3com-2H2, 7F3com-3H5, or 7F3com-3D4. 
     
     
         33 . The IL-9 antibody of  claim 29 , wherein the antibody further comprises a VL CDR3 having the amino acid sequence of a VL CDR3 of 4D4, 4D4H2-1 D11, 4D4com-XF9, 4D4com-2F9, 7F3, 71A10, 22D3, 7F3com-2H2, 7F3com-3H5, or 7F3com-3D4. 
     
     
         34 . The IL-9 antibody of  claim 30 , wherein the antibody further comprises a VL CDR3 having the amino acid sequence of a VL CDR3 of 4D4, 4D4H2-1 D11, 4D4com-XF9, 4D4com-2F9, 7F3, 71A10, 22D3, 7F3com-2H2, 7F3com-3H5, or 7F3com-3D4. 
     
     
         35 - 42 . (canceled) 
     
     
         43 . The IL-9 antibody of  claim 28 , wherein the antibody further comprises a VH CDR1 having the amino acid sequence of a VH CDR1 of 4D4, 4D4H2-1 D11, 4D4com-XF9, 4D4com-2F9, 7F3, 71A10, 22D3, 7F3com-2H2, 7F3com-3H5, or 7F3com-3D4. 
     
     
         44 . The IL-9 antibody of  claim 28 , wherein the antibody further comprises a VH CDR2 having the amino acid sequence of a VH CDR2 of 4D4, 4D4H2-1 D11, 4D4com-XF9, 4D4com-2F9, 7F3, 71A10, 22D3, 7F3com-2H2, 7F3com-3H5, or 7F3com-3D4. 
     
     
         45 . The IL-9 antibody of  claim 28 , wherein the antibody further comprises a VH CDR3 having the amino acid sequence of a VH CDR3 of 4D4, 4D4H2-1 D11, 4D4com-XF9, 4D4com-2F9, 7F3, 71A10, 22D3, 7F3com-2H2, 7F3com-3H5, or 7F3com-3D4. 
     
     
         46 . The IL-9 antibody of  claim 43 , wherein the antibody further comprises a VH CDR2 having an amino acid sequence of a VH CDR2 of 4D4, 4D4H2-1 D11, 4D4com-XF9, 4D4com-2F9, 7F3, 71A10, 22D3, 7F3com-2H2, 7F3com-3H5, or 7F3com-3D4. 
     
     
         47 . The IL-9 antibody of  claim 43 , wherein the antibody further comprises a VH CDR3 having an amino acid sequence of a VH CDR3 of 4D4, 4D4H2-1 D11, 4D4com-XF9, 4D4com-2F9, 7F3, 71A10, 22D3, 7F3com-2H2, 7F3com-3H5, or 7F3com-3D4. 
     
     
         48 . The IL-9 antibody of  claim 44 , wherein the antibody further comprises a VH CDR3 having an amino acid sequence of a VH CDR3 of 4D4, 4D4H2-1 D11, 4D4com-XF9, 4D4com-2F9, 7F3, 71A10, 22D3, 7F3com-2H2, 7F3com-3H5, or 7F3com-3D4. 
     
     
         49 - 84 . (canceled) 
     
     
         85 . The IL-9 antibody of  claim 1 ,  2  or  3 , wherein the antibody is a human or humanized antibody. 
     
     
         86 . The IL-9 antibody of  claim 1 ,  2  or  3 , wherein the antibody is conjugated to a detectable substance or a therapeutic agent. 
     
     
         87 . A pharmaceutical composition comprising the IL-9 antibody of  claim 1 ,  2  or  3 , and a pharmaceutically acceptable carrier. 
     
     
         88 . A method for preventing, treating, managing and/or ameliorating a disease or disorder characterized by aberrant expression and/or activity of an IL-9 polypeptide or aberrant expression and/or activity of an IL-9R, said method comprising administering to a subject in need thereof an prophylactically or therapeutically effective amount of the IL-9 antibody of  claim 1 ,  2  or  3 . 
     
     
         89 . A method for preventing, treating, managing and/or ameliorating an inflammatory disorder, autoimmune disorder, a proliferative disorder or respiratory infection or one or more symptoms thereof, said comprising administering to a subject in need thereof a dosage of a prophylactically or therapeutically effective amount of the IL-9 antibody of  claim 1 ,  2  or  3 . 
     
     
         90 . The method of  claim 89 , wherein the respiratory infection is caused by a virus or bacteria. 
     
     
         91 . The method of  claim 89 , wherein the virus is respiratory syncytial virus, parainfluenza virus or human metapneumovirus. 
     
     
         92 . The method of  claim 89 , wherein the inflammatory disorder is asthma, an allergy, arthritis or a disorder characterized by type 2-mediated inflammation. 
     
     
         93 . The method of  claim 89 , wherein the autoimmune disorder is rheumatoid arthritis or multiple sclerosis. 
     
     
         94 . The method of  claim 89  further comprising a dosage of a prophylactically or therapeutically effective amount of one or more prophylactic or therapeutic agents other than an IL-9 antibody. 
     
     
         95 . The method of  claim 94 , wherein at least one of the prophylactic or therapeutic agents is an anti-angiogenic agent, a TNF-α antagonist, an immunomodulatory agent, or an anti-inflammatory agent. 
     
     
         96 . The method of  claim 95 , wherein the anti-angiogenic agent is VITAXIN™. 
     
     
         97 . The method of  claim 95 , wherein the immunomodulatory agent is MEDI-507 or an anti-Epha2 antibody. 
     
     
         98 . The method of  claim 89 , wherein the IL-9 antibody is administered parenterally, intranasally or orally. 
     
     
         99 . The method of  claim 89 , wherein the subject is refractory to conventional therapies for the disease or disorder. 
     
     
         100 . A method of diagnosing, prognosing, or monitoring a disorder or disease characterized by aberrant expression and/or activity of an IL-9 polypeptide or aberrant expression and/or activity of an IL-9R comprising: (a) assaying the level of IL-9 in cells or a tissue sample of a subject using the IL-9 antibody claim of 1, 2 or 3; and (b) comparing the assayed level of IL-9 with a control level, whereby an increase or decrease in the assayed level of IL-9 compared to the control level of IL-9 is indicative of said disorder or disease. 
     
     
         101 . A kit comprising the antibody of  claim 1 ,  2  or  3  and instructions for use, in one or more containers. 
     
     
         102 . An article of manufacture comprising a packaging material and a pharmaceutical agent contained within said packaging material, wherein said pharmaceutical agent comprises the IL-9 antibody of  claim 1 ,  2  or  3  and a pharmaceutically acceptable carrier. 
     
     
         103 - 110 . (canceled) 
     
     
         111 . An isolated antibody comprising a VH domain, wherein the antibody immunospecifically binds to a human IL-9 polypeptide and the VH domain comprises:
 (a) a VH CDR1 having the amino acid sequence of the VH CDR1 of the antibody encoded by the vector deposited as ATCC deposit No. PTA-5913 with less than 2 amino acid substitutions;   (b) a VH CDR2 having the amino acid sequence of the VH CDR2 of the antibody encoded by the vector deposited as ATCC deposit No. PTA-5913 with less than 2 amino acid substitutions; and   (c) a VH CDR3 having the amino acid sequence of the VH CDR3 of the antibody encoded by the vector deposited as ATCC deposit No. PTA-5913 with less than 2 amino acid substitutions.   
     
     
         112 . An isolated antibody comprising a VL domain, wherein the antibody immunospecifically binds to a human IL-9 polypeptide and the VL domain comprises:
 (a) a VL CDR1 having the amino acid sequence of the VL CDR1 of the antibody encoded by the vector deposited as ATCC deposit No. PTA-5913 with less than 2 amino acid substitutions;   (b) a VL CDR1 having the amino acid sequence of the VL CDR2 of the antibody encoded by the vector deposited as ATCC deposit No. PTA-5913 with less than 2 amino acid substitutions; and   (c) a VL CDR3 having the amino acid sequence of the VL CDR3 of the antibody encoded by the vector deposited as ATCC deposit No. PTA-5913 with less than 2 amino acid substitutions.   
     
     
         113 . The isolated antibody of  claim 111  further comprising a VL domain. 
     
     
         114 . The isolated antibody of  claim 112  further comprising a VH domain. 
     
     
         115 . The isolated antibody of  claim 113 , wherein the VL domain comprises:
 (a) a VL CDR1 having the amino acid sequence of the VL CDR1 of the antibody encoded by the vector deposited as ATCC deposit No. PTA-5913 with less than 2 amino acid substitutions;   (b) a VL CDR2 having the amino acid sequence of the VL CDR2 of the antibody encoded by the vector deposited as ATCC deposit No. PTA-5913 with less than 2 amino acid substitutions; and   (c) a VL CDR3 having the amino acid sequence of the VL CDR3 of the antibody encoded by the vector deposited as ATCC deposit No. PTA-5913 with less than 2 amino acid substitutions.   
     
     
         116 . A pharmaceutical composition comprising the antibody of any one of  claims 111 ,  112 ,  113 ,  114 , or  115 .