Antibodies that specifically bind to GMAD

Abstract

The present invention relates to antibodies and related molecules that immunospecifically bind to GMAD. Such antibodies have uses, for example, in the prevention and treatment of both insulin- and non insulin-dependent diabetes mellitus (i.e. Type I and Type II diabetes) and other related disorders. The invention also relates to nucleic acid molecules encoding anti-GMAD antibodies, vectors and host cells containing these nucleic acids, and methods for producing the same. The present invention relates to methods and compositions for preventing, detecting, diagnosing, treating or ameliorating a disease or disorder, especially diabetes and other related disorders, comprising administering to an animal, preferably a human, an effective amount of one or more antibodies or fragments or variants thereof, or related molecules, that immunospecifically bind to GMAD.

1 .- 43 . (canceled) 
     
     
         44 . An isolated antibody or fragment thereof comprising:
 (a) an amino acid sequence comprising the VH domain of SEQ ID NO: 43; and   (b) an amino acid sequence comprising the VL domain of SEQ ID NO: 43;   
       wherein said antibody or fragment thereof specifically binds a GMAD polypeptide. 
     
     
         45 . The antibody or fragment thereof of  claim 44 , wherein the antibody or fragment thereof is selected from the group consisting of:
 (a) a whole immunoglobulin molecule;   (b) an scFv;   (c) a Fab fragment;   (d) an Fab′ fragment;   (e) an F(ab′) 2 ;   (f) an Fv; and   (g) a disulfide linked Fv.   
     
     
         46 . The antibody or fragment thereof of  claim 44  wherein the antibody or fragment thereof is monoclonal, human, chimeric, or humanized. 
     
     
         47 . The antibody or fragment thereof of  claim 44  which comprises a heavy chain immunoglobulin constant domain selected from the group consisting of:
 (a) a human IgM constant domain;   (b) a human IgG1 constant domain;   (c) a human IgG2 constant domain;   (d) a human IgG3 constant domain;   (e) a human IgG4 constant domain; and   (f) a human IgA constant domain.   
     
     
         48 . The antibody or fragment thereof of  claim 44  which comprises a light chain immunoglobulin constant domain selected from the group consisting of:
 (a) a human Ig kappa constant domain; and   (b) a human Ig lambda constant domain.   
     
     
         49 . The antibody or fragment thereof of  claim 44  wherein the antibody or fragment thereof is conjugated to a detectable label. 
     
     
         50 . The antibody or fragment thereof of  claim 49 , wherein the detectable label is a radiolabel. 
     
     
         51 . The antibody or fragment thereof of  claim 50 , wherein the radiolabel is  125 I,  131 I,  111 In,  90 Y,  99 Tc,  177 Lu,  166 Ho, or  153 Sm. 
     
     
         52 . The antibody or fragment thereof of  claim 49 , wherein the detectable label is an enzyme, a fluorescent label, a luminescent label, or a bioluminescent label. 
     
     
         53 . The antibody or fragment thereof of  claim 44  wherein the antibody or fragment thereof is biotinylated. 
     
     
         54 . The antibody or fragment thereof of  claim 44  wherein the antibody or fragment thereof is conjugated to a therapeutic or cytotoxic agent. 
     
     
         55 . The antibody or fragment thereof of  claim 54 , wherein the therapeutic or cytotoxic agent is an anti-metabolite, an alkylating agent, an antibiotic, a growth factor, a cytokine, an anti-angiogenic agent, an anti-mitotic agent, an anthracycline, a toxin, or an apoptotic agent. 
     
     
         56 . The antibody or fragment thereof of  claim 44  wherein the antibody or fragment thereof is attached to a solid support. 
     
     
         57 . The antibody or fragment thereof of  claim 44  wherein the antibody or fragment thereof specifically binds a GMAD polypeptide in a Western blot. 
     
     
         58 . The antibody or fragment thereof of  claim 44  wherein the antibody or fragment thereof specifically binds a GMAD polypeptide in an ELISA. 
     
     
         59 . An isolated cell that produces the antibody or fragment thereof of  claim 44 . 
     
     
         60 . The antibody or fragment thereof of  claim 44  wherein the antibody or fragment thereof inhibits the activity of a GMAD polypeptide or a fragment thereof. 
     
     
         61 . The antibody or fragment thereof of  claim 60  wherein the antibody or fragment thereof diminishes or abolishes the ability of a GMAD polypeptide or a fragment thereof to bind to its receptor. 
     
     
         62 . The antibody or fragment thereof of  claim 60  wherein the antibody or fragment thereof diminishes or abolishes the ability of a GMAD polypeptide or a fragment thereof to inhibit insulin action. 
     
     
         63 . A kit comprising the antibody or fragment thereof of  claim 44 . 
     
     
         64 . The kit of  claim 63 , comprising a control antibody. 
     
     
         65 . The kit of  claim 63 , wherein the antibody or fragment thereof is coupled or conjugated to a detectable label. 
     
     
         66 . An isolated antibody comprising SEQ ID NO: 43, wherein the antibody specifically binds a GMAD polypeptide.