US2009142351A1PendingUtilityA1

Human and rat PGC-3, PPAR-gamma coactivations and splice variants thereof

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Assignee: ASTRAZENECA ABPriority: Sep 15, 2000Filed: Oct 29, 2007Published: Jun 4, 2009
Est. expirySep 15, 2020(expired)· nominal 20-yr term from priority
Inventors:Kevin HartCarl Thomas MontagueAntonio Vidal-Puig
A61P 3/04A61P 9/10A61P 3/10A61P 3/06C07K 14/5759A61P 3/00A61K 38/00
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Claims

Abstract

A novel gene PGC-3, and its role in regulating the transcriptional activity of PPARγ in adipose tissue. PGC-3 is highly expressed in human white adipose tissue and has utility in the development of new therapeutic agents for use in the treatment of obesity and other related disorders such as non-insulin dependent diabetes mellitus, insulin resistance syndrome, dyslipidemia, and atherosclerosis.

Claims

exact text as granted — not AI-modified
1 . An antibody or antigen-binding fragment thereof, wherein the antibody specifically binds a PGC-3 polypeptide selected from any one of
 (a) a human PGC-3a polypeptide or a variant having at least about 90% homology to a member selected from (SEQ ID NO:2, SEQ ID NO:2 positions 1-600, SEQ ID NO:2 positions 400-1002, SEQ ID NO:2 positions 200-800), or a biologically active fragment thereof;   or   (b) a human PGC-3b polypeptide or a variant having at least about 90% homology to a member selected from (SEQ ID NO:4, SEQ ID NO:4 positions 1-600, SEQ ID NO:4 positions 400-996, SEQ ID NO:4 positions 200-800), or a biologically active fragment thereof;   or   (c) a human PGC-3c polypeptide or a variant having at least about 90% homology to a member selected from (SEQ ID NO:8, SEQ ID NO:8 positions 1-600, SEQ ID NO:8 positions 400-1023, SEQ ID NO:8 positions 200-800), or a biologically active fragment thereof.   
     
     
         2 . The antibody or antigen-binding fragment thereof of  claim 1 , wherein the antibody binds a polypeptide comprising a human PGC-3a polypeptide or a variant having at least about 90% homology to a member selected from (SEQ ID NO:2, SEQ ID NO:2 positions 1-600, SEQ ID NO:2 positions 400-1002, SEQ ID NO:2 positions 200-800), or a biologically active fragment thereof. 
     
     
         3 . The antibody or antigen-binding fragment thereof of  claim 1 , wherein the antibody binds a polypeptide comprising the human PGC-3b amino acid sequence set out in SEQ ID NO:4 or a variant of SEQ ID NO:4 having at least about 90% homology to a member selected from (SEQ ID NO:4 positions 1-600, SEQ ID NO:4 positions 400-996, SEQ ID NO:4 positions 200-800), or a biologically active fragment thereof. 
     
     
         4 . The antibody or antigen-binding fragment thereof of  claim 1 , wherein the antibody binds a polypeptide comprising a human PGC-3c polypeptide or a variant having at least about 90% homology to a member selected from (SEQ ID NO:8, SEQ ID NO:8 positions 1-600, SEQ ID NO:8 positions 400-1023, SEQ ID NO:8 positions 200-800), or a biologically active fragment thereof. 
     
     
         5 . The antibody or antigen-binding fragment thereof according to  claim 1 , wherein said antibody or antibody fragment is selected from a polyclonal antibody, a monoclonal antibody or antibody fragment, F(ab′) 2 , Fab and single chain Fv. 
     
     
         6 . The antibody or antigen-binding fragment thereof according to  claim 5 , wherein said antibody is a monoclonal antibody. 
     
     
         7 . The antibody or antigen-binding fragment thereof according to  claim 5 , wherein said antibody is a polyclonal antibody. 
     
     
         8 . The antibody or antigen-binding fragment thereof according to  claim 1 , wherein the antibody binds to a PGC-3 polypeptide with a K a  of greater than or equal to about 10 7 M −1 . 
     
     
         9 . The antibody or antigen-binding fragment thereof according to  claim 1 , wherein the antibody modulates the activity of PGC-3. 
     
     
         10 . The antibody or antigen-binding fragment thereof according to  claim 9 , wherein the antibody stimulates the activity of PGC-3. 
     
     
         11 . The antibody or antigen-binding fragment thereof according to  claim 9 , wherein the antibody inhibits the activity of PGC-3. 
     
     
         12 . The antibody or antigen-binding fragment thereof according to  claim 9 , wherein the activity of PGC-3 is mediating cell processes related to a condition selected from insulin resistance syndrome, non-insulin dependent diabetes mellitus, dyslipidemia, obesity or atherosclerosis. 
     
     
         13 . The antibody or antigen-binding fragment thereof according to  claim 1 , in admixture with one or more pharmaceutically acceptable diluents or carriers. 
     
     
         14 . The antibody or antigen-binding fragment thereof according to  claim 13 , wherein said PGC-3 antibody modulates the activity of PGC-3. 
     
     
         15 . The antibody or antigen-binding fragment thereof according to  claim 14 , wherein the antibody stimulates the activity of PGC-3. 
     
     
         16 . The antibody or antigen-binding fragment thereof according to  claim 14 , wherein the antibody inhibits the activity of PGC-3. 
     
     
         17 . The antibody or antigen-binding fragment thereof according to  claim 13 , wherein said antibody or antibody fragment is selected from a polyclonal antibody, a monoclonal antibody or antibody fragment, F(ab′) 2 , Fab and single chain Fv. 
     
     
         18 . The antibody or antigen-binding fragment thereof according to  claim 17 , wherein said antibody is a monoclonal antibody. 
     
     
         19 . The antibody or antigen-binding fragment thereof according to  claim 17 , wherein said antibody is a polyclonal antibody. 
     
     
         20 . A method of treating a metabolic disease or medical condition mediated alone or in part by PGC-3, which comprises administering to a warm-blooded animal requiring such treatment an effective amount of a PGC-3 antibody or antigen-binding fragment thereof as claimed in  claim 1 . 
     
     
         21 . The method of  claim 20 , wherein the metabolic disease or medical condition mediated alone or in part by PGC-3 is selected from insulin resistance syndrome, non-insulin dependent diabetes mellitus, dyslipidemia, obesity or atherosclerosis. 
     
     
         22 . The method of  claim 20 , wherein said PGC-3 antibody or antigen-binding fragment thereof modulates the activity of PGC-3. 
     
     
         23 . The method of  claim 22 , wherein the antibody or antigen-binding fragment thereof stimulates the activity of PGC-3. 
     
     
         24 . The method of  claim 22 , wherein the antibody or antigen-binding fragment thereof inhibits the activity of PGC-3. 
     
     
         25 . The method of  claim 20 , wherein said antibody or antibody fragment thereof is selected from a polyclonal antibody, a monoclonal antibody or antibody fragment, F(ab′) 2 , Fab and single chain Fv.

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