Anti-trkb monoclonal antibodies and uses thereof

Abstract

The present invention provides monoclonal antibodies for human TrkB. In certain embodiments the inventive antibodies bind and activate human TrkB. In certain embodiments the inventive antibodies are selective for human TrkB in that they do not bind (or activate) human TrkA or human TrkC. In some embodiments the inventive monoclonal antibodies cross-react with murine TrkB. Humanized or veneered versions of the inventive antibodies are also encompassed. Pharmaceutical compositions that comprise inventive antibodies are provided as are methods for preparing the inventive antibodies and methods of using these for treatment, detection or purification purposes.

1 . A monoclonal antibody that binds human TrkB. 
     
     
         2 . The monoclonal antibody of  claim 1 , wherein the binding with human TrkB has an ED 50  in the range of about 10 μM to about 500 nM. 
     
     
         3 - 5 . (canceled) 
     
     
         6 . The monoclonal antibody of  claim 1 , wherein the monoclonal antibody activates human TrkB with an EC 50  in the range of about 10 μM to about 500 nM. 
     
     
         7 - 9 . (canceled) 
     
     
         10 . The monoclonal antibody of  claim 1 , wherein the monoclonal antibody does not bind and/or does not activate human TrkA. 
     
     
         11 . The monoclonal antibody of  claim 10 , wherein the monoclonal antibody exhibits no detectable binding with human TrkA and/or does not cause any detectable activation of human TrkA at antibody concentrations above about 1 nM. 
     
     
         12 - 14 . (canceled) 
     
     
         15 . The monoclonal antibody of  claim 1 , wherein the monoclonal antibody does not bind and/or does not activate human TrkC. 
     
     
         16 . The monoclonal antibody of  claim 15 , wherein the monoclonal antibody exhibits no detectable binding with human TrkC and/or does not cause any detectable activation of human TrkC at antibody concentrations above about 1 nM. 
     
     
         17 - 19 . (canceled) 
     
     
         20 . The monoclonal antibody of  claim 10 , wherein the monoclonal antibody does not bind and/or does not activate human TrkC. 
     
     
         21 . The monoclonal antibody of  claim 1 , wherein the monoclonal antibody blocks the binding between BDNF and human TrkB. 
     
     
         22 . The monoclonal antibody of  claim 21 , wherein the monoclonal antibody blocks the binding between BDNF and human TrkB with an IC 50  in the range of about 100 μM to about 500 nM. 
     
     
         23 . (canceled) 
     
     
         24 . (canceled) 
     
     
         25 . The monoclonal antibody of  claim 1 , wherein the monoclonal antibody does not block the binding between BDNF and human TrkB. 
     
     
         26 - 37 . (canceled) 
     
     
         38 . The monoclonal antibody of  claim 1 , wherein the monoclonal antibody binds one or both of the epitopes of human TrkB with sequences KNEYGKD (SEQ ID NO:7) and KGNPKP (SEQ ID NO:8). 
     
     
         39 . (canceled) 
     
     
         40 . The monoclonal antibody of  claim 1 , wherein the monoclonal antibody binds an epitope of human TrkB with the sequence ENLVGED (SEQ ID NO: 10) and optionally an epitope of human TrkB with the sequence AGDPVP (SEQ ID NO:11). 
     
     
         41 . (canceled) 
     
     
         42 . A monoclonal antibody that is produced from the hybridoma deposited with the ATCC on Aug. 18, 2005 and having ATCC patent deposit designation PTA-6948 or from a progenitor cell thereof. 
     
     
         43 . A monoclonal antibody that binds to the same epitope as a monoclonal antibody produced from the hybridoma deposited with the ATCC on Aug. 18, 2005 and having ATCC patent deposit designation PTA-6949. 
     
     
         44 . The monoclonal antibody of  claim 1 , wherein the monoclonal antibody binds to the same epitope as the monoclonal antibody of  claim 42 . 
     
     
         45 . (canceled) 
     
     
         46 . A hybridoma that produces a monoclonal antibody according to  claim 1 . 
     
     
         47 - 60 . (canceled) 
     
     
         61 . A method of activating human TrkB in an individual, comprising: administering to an individual, a therapeutically effective amount of a monoclonal antibody of  claim 1 . 
     
     
         62 . The method of  claim 61 , wherein said individual is suffering from a neurological condition which requires activation of TrkB. 
     
     
         63 . The method of  claim 61 , wherein the nervous system of said individual has been injured by a wound, surgery, ischemia, infection, a metabolic disease, malnutrition, a malignant tumor or a toxic drug. 
     
     
         64 . The method of  claim 61 , wherein said individual has suffered a stroke, a spinal cord injury, or an axotomy. 
     
     
         65 . The method of  claim 61 , wherein said individual is suffering from a congenital or neurodegenerative condition. 
     
     
         66 . The method of  claim 65 , wherein said condition is selected from the group consisting of Alzheimer's disease, Parkinson's disease, Huntington's chorea, and amyotrophic lateral sclerosis (ALS). 
     
     
         67 - 68 . (canceled) 
     
     
         69 . A method comprising:
 combining a monoclonal antibody of  claim 1  with a sample that includes an amount of human TrkB under conditions that allow specific binding between the monoclonal antibody and human TrkB; and   detecting the specific binding, thereby indicating the presence of human TrkB in the sample.   
     
     
         70 . A method comprising:
 combining a monoclonal antibody of  claim 1  with a sample that includes an amount of human TrkB under conditions that allow specific binding between the monoclonal antibody and human TrkB, thereby producing an antibody-TrkB complex;   separating the antibody-human TrkB complex from the remainder of the sample; and   separating the antibody from human TrkB, thereby obtaining purified human TrkB.