Methods and compositions relating to anti-chi3l1 antibody reagents

Abstract

Described herein are methods and compositions relating to anti-Chi3L1 antibodies, antibody reagents, and antigen-binding fragments thereof which display superior properties, e.g., high sensitivity, high specificity, high binding affinity, neutralization activity ex vivo and in vivo (e.g., blocks Chi3L1-induced MAPK and AKT signaling). Methods of treatment, e.g., of treating cancer, obesity, and/or asthma by administering the compounds described herein are also provided.

1 - 30 . (canceled) 
     
     
         31 . A method of treating obesity or preventing weight gain in a subject in need thereof, the method comprising administering, to the subject, an immunoglobulin antibody that specifically binds an CHI3L1 polypeptide, said immunoglobulin antibody comprising complementarity determining regions (CDRs) of:
 a. a light chain CDR1 having the amino acid sequence of SEQ ID NO: 4;   b. a light chain CDR2 having the amino acid sequence of SEQ ID NO: 5;   c. a light chain CDR3 having the amino acid sequence of SEQ ID NO: 6;   d. a heavy chain CDR1 having the amino acid sequence of SEQ ID NO: 1;   e. a heavy chain CDR2 having the amino acid sequence of SEQ ID NO: 2; and   f. a heavy chain CDR3 having the amino acid sequence of SEQ ID NO: 3.   
     
     
         32 . The method of  claim 31 , wherein the immunoglobulin antibody comprises a heavy chain sequence having the amino acid sequence of SEQ ID NO: 36 or a light chain sequence having the amino acid sequence of SEQ ID NO: 38. 
     
     
         33 . The method of  claim 31 , wherein the immunoglobulin antibody comprises a heavy chain sequence having the amino acid sequence of SEQ ID NO: 36 and a light chain sequence having the amino acid sequence of SEQ ID NO: 38. 
     
     
         34 . The method of  claim 31 , wherein immunoglobulin antibody comprises a conservative substitution relative to the heavy chain sequence having the amino acid sequence of SEQ ID NO: 36 or the light chain sequence having the amino acid sequence of SEQ ID NO: 38, wherein the conservative substitution is in a sequence not comprised by a CDR. 
     
     
         35 . The method of  claim 31 , wherein the immunoglobulin antibody is selected from the group consisting of: a bivalent IgG which is fully humanized except for the CDR sequences; a monoclonal antibody, a CDR-grafted antibody, and a humanized antibody. 
     
     
         36 . The method of  claim 31 , wherein the immunoglobulin antibody is administered in a pharmaceutical composition comprising the antibody and a pharmaceutically acceptable carrier. 
     
     
         37 . The method of  claim 31 , wherein the subject is a subject determined to have a level of CHI3L1 that is increased compared to a reference level from healthy subjects. 
     
     
         38 . The method of  claim 37 , wherein the CHI3L1 is circulating CHI3L1. 
     
     
         39 . The method of  claim 31 , wherein the subject is a subject determined to have a level of CHI3L1 that is increased compared to the level of CHI3L1 in a prior sample obtained from the subject. 
     
     
         40 . The method of  claim 39 , wherein the CHI3L1 is circulating CHI3L1. 
     
     
         41 . A method of promoting weight or fat loss in a subject in need thereof, the method comprising administering, to the subject, an immunoglobulin antibody that specifically binds an CHI3L1 polypeptide, said immunoglobulin antibody comprising complementarity determining regions (CDRs) of:
 a. a light chain CDR1 having the amino acid sequence of SEQ ID NO: 4;   b. a light chain CDR2 having the amino acid sequence of SEQ ID NO: 5;   c. a light chain CDR3 having the amino acid sequence of SEQ ID NO: 6;   d. a heavy chain CDR1 having the amino acid sequence of SEQ ID NO: 1;   e. a heavy chain CDR2 having the amino acid sequence of SEQ ID NO: 2; and   f. a heavy chain CDR3 having the amino acid sequence of SEQ ID NO: 3.   
     
     
         42 . The method of  claim 41 , wherein the immunoglobulin antibody comprises a heavy chain sequence having the amino acid sequence of SEQ ID NO: 36 or a light chain sequence having the amino acid sequence of SEQ ID NO: 38. 
     
     
         43 . The method of  claim 41 , wherein the immunoglobulin antibody comprises a heavy chain sequence having the amino acid sequence of SEQ ID NO: 36 and a light chain sequence having the amino acid sequence of SEQ ID NO: 38. 
     
     
         44 . The method of  claim 41 , wherein the immunoglobulin antibody comprises a conservative substitution relative to the heavy chain sequence having the amino acid sequence of SEQ ID NO: 36 or the light chain sequence having the amino acid sequence of SEQ ID NO: 38, wherein the conservative substitution is in a sequence not comprised by a CDR. 
     
     
         45 . The method of  claim 41 , wherein the immunoglobulin antibody is selected from the group consisting of: a bivalent IgG which is fully humanized except for the CDR sequences; a monoclonal antibody, a CDR-grafted antibody, and a humanized antibody. 
     
     
         46 . The method of  claim 41 , wherein the bivalent IgG antibody is administered in a pharmaceutical composition comprising the antibody and a pharmaceutically acceptable carrier. 
     
     
         47 . The method of  claim 41 , wherein the subject is a subject determined to have a level of CHI3L1 that is increased compared to a reference level from healthy subjects. 
     
     
         48 . The method of  claim 47 , wherein the CHI3L1 is circulating CHI3L1. 
     
     
         49 . The method of  claim 41 , wherein the subject is a subject determined to have a level of CHI3L1 that is increased compared to the level of CHI3L1 in a prior sample obtained from the subject. 
     
     
         50 . The method of  claim 49 , wherein the CHI3L1 is circulating CHI3L1.