Chimeric fibroblast growth factors with altered receptor specificity

Abstract

The present invention is directed to novel chimeric fibroblast growth factor (FGF) polypeptides, novel DNA encoding chimeric FGF polypeptides, and to the recombinant production of chimeric FGF polypeptides, and to methods, compositions and assays utilizing chimeric FGF polypeptides for the therapeutic treatment of metabolic-related disorders and other conditions, and for producing pharmaceutically active compositions including chimeric FGF polypeptides, the compositions having therapeutic and pharmacologic properties including those associated with the treatment of metabolic-related disorders and other conditions.

1 - 50 . (canceled) 
     
     
         51 . A chimeric FGF19 polypeptide comprising an amino acid sequence that has at least 90% identity to the amino acid sequence of SEQ ID NO:5. 
     
     
         52 . The chimeric FGF19 polypeptide of  claim 51 , wherein the chimeric hFGF19 polypeptide is fused to a second polypeptide, the second polypeptide is selected from the group consisting of: the Fc portion of an immunoglobulin, an analog of the Fc portion of an immunoglobulin and one or more fragments of the Fc portion of an immunoglobulin. 
     
     
         53 . The chimeric FGF19 polypeptide of  claim 52 , wherein the immunoglobulin is selected from the group consisting of: IgG-1, IgG-2, IgG-3, IgG-4, IgA-1, IgA-2, IgE, IgD and IgM. 
     
     
         54 . The chimeric FGF19 polypeptide of  claim 52 , wherein the Fc portion is human or humanized. 
     
     
         55 . The chimeric FGF19 polypeptide of  claim 52 , wherein the C-terminus of the chimeric hFGF19 polypeptide is fused to the N-terminus of the second polypeptide. 
     
     
         56 . The chimeric FGF19 polypeptide of  claim 52 , wherein the C-terminus of the chimeric hFGF19 polypeptide is fused to the N-terminus of the second polypeptide via a linker, the linker is selected from the group consisting of: a [Gly]n linker, a [Gly3Ser]m linker and a [Gly4Ser]m linker, wherein n is an integer from 1-30 and m is an integer from 1-6. 
     
     
         57 . A pharmaceutical composition comprising:
 (a) a therapeutically effective amount of the chimeric FGF19 polypeptide of claim  1 ; and   (b) an acceptable pharmaceutical carrier.   
     
     
         58 . An isolated nucleic acid molecule comprising (a) a DNA molecule encoding a polypeptide comprising an amino acid sequence that has at least 90% identity to the amino acid sequence of SEQ ID NO:5. 
     
     
         59 . The isolated nucleic acid of  claim 58 , wherein the encoded polypeptide further comprises the amino acid residues corresponding to the Fc portion of an immunoglobulin. 
     
     
         60 . An expression system comprising the nucleic acid molecule of  claim 58 . 
     
     
         61 . A host cell comprising the expression system of  claim 60 . 
     
     
         62 . A host cell comprising the nucleic acid molecule of  claim 58 . 
     
     
         63 . A process for producing an isolated polypeptide comprising: culturing the host cell of  claim 61  under conditions suitable for expression of the encoded polypeptide; and recovering the encoded polypeptide from the cell culture. 
     
     
         64 . A process for producing an isolated polypeptide comprising: culturing the host cell of  claim 62  under conditions suitable for expression of the encoded polypeptide; and recovering the encoded polypeptide from the cell culture. 
     
     
         65 . An isolated polypeptide produced by the process of  claim 63 . 
     
     
         66 . An isolated polypeptide produced by the process of  claim 64 .