PANCREATIC POLYPEPTIDE FAMILY MOTIFS, POLYPEPTIDES AND METHODS COMPRISING THE SAME
First Claim
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1. A PPF polypeptide comprising an amino acid sequence of Formula (VI):
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Abstract
The present invention provides novel Pancreatic Polypeptide Family (“PPF”) polypeptides and methods for their use.
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53 Claims
- 1. A PPF polypeptide comprising an amino acid sequence of Formula (VI):
- 2. A PPF polypeptide comprising an amino acid sequence of Formula (VII):
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3. A PPF polypeptide comprising:
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an N-terminal fragment consisting essentially of the first 17 amino acid residues of native human PYY (SEQ ID NO;
2); anda C-terminal fragment consisting essentially of amino acid residues 18-36 of native human NPY (SEQ ID NO;
4), wherein the N-terminal and C-terminal fragments are covalently linked, wherein no more than two amino acid residues at the N-terminus of the PYY fragment may be deleted or absent, and wherein no more than nine amino acid substitutions may be made in each of the N-terminal and C-terminal fragments;with the proviso that said PPF polypeptide does not include a modified natural amino acid and with the further proviso that said PPF polypeptide is not a native PPF polypeptide, PP, NPY(1-36), NPY(3-36), PYY(1-36), PYY(3-36), NPY(2-36), NPY(4-36), PYY(2-36), PYY(4-36), PP(2-36), PP(3-36), PP(4-36), Tyr1hPP, Lys4hPP, Asn7hPP, Arg19hPP, Tyr21hPP, Glu21hPP, Ala23hPP, Gln23hPP, Gln34hPP, Phe6Arg19hPP, Phe6Tyr21hPP, Phe6Glu21hPP, Phe6Ala23hPP, Phe6Gln23hPP, Pro13Ala14hPP, Ile31Gln34PP, Arg19Tyr20Tyr21Ser22Ala23hPP, Lys4Arg19Tyr20Tyr21Ser22Ala23hPP, Lys4Arg19Tyr20Tyr21Ser22Ala23hPP(2-36), Ala1NPY, Tyr1NPY, Ala2NPY, Leu2NPY, Phe2NPY, His2NPY, Ala3NPY, Ala4NPY, Ala6NPY, Tyr7pNPY, Ala7NPY, Ala9NPY, Ala1NPY, Ala11NPY, Gly12NPY, Ala13NPY, Gly14NPY, Ala15NPY, Ala16NPY, Ala17NPY, Gly18NPY, Ala19NPY, Lys19NPY, Ala20NPY, Ala21NPY, Ala22NPY, Gly23NPY, Ala24NPY, Trp24pNPY, Ala25NPY, Lys25NPY, Ala26NPY, Ala27NPY, Phe27NPY, Ala28NPY, Ala29NPY, Gln29NPY, Ala30NPY, Phe30NPY, Ala31NPY, Trp31pNPY, Ala32NPY, Trp32NPY, Ala33NPY, Lys33NPY, Ala34NPY, Pro34NPY, Leu34NPY, Ala35NPY, Lys35NPY, Ala36NPY, Phe36NPY, His36NPY, Glu4Pro34pNPY, Arg6Pro34pNPY, Phe6Pro34pNPY, Cys6Pro34pNPY, Asn6Pro34pNPY, Phe7Pro34pNPY, Arg7Pro34pNPY, Cys7Pro34pNPY, Asp7Pro34pNPY, Phe8Pro34pNPY, Arg8Pro34pNPY, Cys8Pro34pNPY, Asp8Pro34pNPY, Asn8Pro34pNPY, Pro11Pro34pNPY, Ser13Pro14pNPY, Trp24,31pNPY, Ala31Pro32pNPY, Cys31Pro34pNPY, Leu31Pro34NPY, Phe32Pro34pNPY, Ala21,25Pro34pNPY, Pro11Tyr13Pro14Pro34pNPY, Ahx(9-22)pNPY, Ahx(9-17)pNPY, des-AA(10-20)-Cys7,21Pro34-pNPY, des-AA(10-17)-pNPY, des-AA(10-17)-Cys2,27-pNPY, des-AA(10-17)-Ala7,21-pNPY, des-AA(10-17)-Cys7,21-pNPY, des-AA(10-17)-Glu7Lys21-pNPY, des-AA(10-17)Cys7,21Pro34pNPY, des-AA(10-17)Glu7Lys21Pro34pNPY, des-AA(10-17)Cys7,21Leu31Pro34pNPY, des-AA(11-17)Cys7,21Pro34pNPY, Pro34PYY, His34PYY, Lys25hPYY(5-36), Arg4hPYY(4-36), Gln4hPYY(4-36), Asn4hPYY(4-36), Lys25hPYY(4-36), Leu3hPYY(3-36), Val3hPYY(3-36), Lys25hPYY(3-36), Tyr1,36pPYY, Pro13Ala14hPYY, Leu31Pro34PYY, hPP(1-7)-pNPY, hPP(1-17)-pNPY, hPP(19-23)-pNPY, hPP(19-23)-Pro34pNPY, hPP(19-23)-His34pNPY, rPP(19-23)-pNPY, rPP(19-23)-Pro34pNPY, rPP(19-23)-His34pNPY, hPP(1-7)-pNPY, hPP(1-17)-pNPY, hPP(1-17)-His34pNPY, pNPY(1-7)-hPP, pNPY(1-7,19-23)-hPP, cPP(1-7)-pNPY(19-23)-hPP, cPP(1-7)-NPY(19-23)-His34hPP, hPP(1-17)-His34pNPY, hPP(19-23)-pNPY, hPP(19-23)-Pro34pNPY, hPP(19-23)-His34pNPY, rPP(19-23)-pNPY, rPP(19-23)-Pro34pNPY, rPP(19-23)-His34pNPY, pNPY(1-7)-hPP, pNPY(19-23)-hPP, pNPY(19-23)-Gln34hPP, pNPY(19-23)-His34hPP, pNPY(19-23)-Phe6Gln34hPP, pNPY(19-23)-Phe6His34hPP, pNPY, cPP(22-23)-Pro34-pNPY, cPP(1-7)-Pro34-pNPY, cPP(20-23)-Pro34-pNPY, cPP(1-7,20-23)-Pro34-pNPY, cPP(1-7)-pNPY(19-23)-hPP, cPP(1-7)-pNPY(19-23)-His34hPP, or cPP(1-7)-gPP(19-23)-hPP, Thr27hPYY(3-36), Ile30hPYY(3-36), Ser32hPYY(3-36), Lys33hPYY(3-36), Asn34hPYY(3-36), Lys35hPYY(3-36), Thr36hPYY(3-36), Lys25Thr27hPYY(3-36), Lys25Ile30hPYY(3-36), Lys25Ser32hPYY(3-36), Lys25Lys33hPYY(3-36), Lys25Asn24hPYY(3-36), Lys25Lys35hPYY(3-36), Lys25Thr36hPYY(3-36), Thr27Ile28hPYY(3-36), Thr27Val28hPYY(3-36), Thr27Gln29hPYY(3-36), Thr27Ile30hPYY(3-36), Thr27Val30hPYY(3-36), Thr27Ile31hPYY(3-36), Thr27Leu31hPYY(3-36), Thr27Ser32hPYY(3-36), Thr27Lys33hPYY(3-36), Thr27Asn34hPYY(3-36), Thr27Lys35hPYY(3-36), Thr27Thr36hPYY(3-36), Thr27Phe36hPYY(3-36), Phe27Ile30hPYY(3-36), Phe27Ser32hPYY(3-36), Phe27Lys33hPYY(3-36), Phe27Asn34hPYY(3-36), Phe27Lys35hPYY(3-36), Phe27Thr36hPYY(3-36), Gln29Ile30hPYY(3-36), Gln29Ser32hPYY(3-36), Gln29Leu33hPYY(3-36), Gln29Asn34hPYY(3-36), Gln29Leu35hPYY(3-36), Gln29Thr36hPYY(3-36), Ile30Ile31hPYY(3-36), Ile30Leu31hPYY(3-36), Ile30Ser32hPYY(3-36), Ile30Lys33hPYY(3-36), Ile30Asn34hPYY(3-36), Ile30Lys35hPYY(3-36), Ile30Thr36hPYY(3-36), Ile30Phe36hPYY(3-36), Val30Ser32hPYY(3-36), Val30Lys33hPYY(3-36), Val30Asn34hPYY(3-36), Val30Lys35hPYY(3-36), Val30Thr36hPYY(3-36), Ile31Ser32hPYY(3-36), Ile31Lys33hPYY(3-36), Ile31Asn34hPYY(3-36), Ile31Lys35hPYY(3-36), Ile31Thr36hPYY(3-36), Ile31Phe36hPYY(3-36), Leu31Ser32hPYY(3-36), Leu31Lys33hPYY(3-36), Leu31Asn34hPYY(3-36), Leu31Lys35hPYY(3-36), Leu31Thr36hPYY(3-36), Ser32Lys33hPYY(3-36), Ser32Asn34hPYY(3-36), Ser32Lys35hPYY(3-36), Ser32Thr36hPYY(3-36), Ser32Phe36hPYY(3-36), Lys33Asn34hPYY(3-36), Lys33Lys35hPYY(3-36), Lys33Thr36hPYY(3-36), Lys33Phe36hPYY(3-36), Asn34Lys35hPYY(3-36), Asn34Phe36hPYY(3-36), Lys35Thr36hPYY(3-36), Lys35Phe36hPYY(3-36), Thr27hPYY(4-36), Phe27hPYY(4-36), Ile28hPYY(4-36), Val28hPYY(4-36), Gln29hPYY(4-36), Ile30hPYY(4-36), Val30hPYY(4-36), Ile31hPYY(4-36), Leu31hPYY(4-36), Ser32hPYY(4-36), Lys33hPYY(4-36), Asn34hPYY(4-36), Lys35hPYY(4-36), Thr36hPYY(4-36), Phe36hPYY(4-36), Lys25Thr27hPYY(4-36), Lys25Phe27hPYY(4-36), Lys25Ile28hPYY(4-36), Lys25Val28hPYY(4-36), Lys25Gln29hPYY(4-36), Lys25Ile30hPYY(4-36), Lys25Val30hPYY(4-36), Lys25Ile31hPYY(4-36), Lys25Leu31hPYY(4-36), Lys25Ser32hPYY(4-36), Lys25Lys33hPYY(4-36), Lys25Asn24hPYY(4-36), Lys25Lys35hPYY(4-36), Lys25Thr36hPYY(4-36), Lys25Phe36hPYY(4-36), Thr27Ile28hPYY(4-36), Thr27Val28hPYY(4-36), Thr27Gln29hPYY(4-36), Thr27Ile30hPYY(4-36), Thr27Val30hPYY(4-36), Thr27Ile31hPYY(4-36), Thr27Leu31hPYY(4-36), Thr27Ser32hPYY(4-36), Thr27Lys33hPYY(4-36), Thr27Asn34hPYY(4-36), Thr27Lys35hPYY(4-36), Thr27Thr36hPYY(4-36), Thr27Phe36hPYY(4-36), Phe27Ile28hPYY(4-36), Phe27Val28hPYY(4-36), Phe27Gln29hPYY(4-36), Phe27Ile30hPYY(4-36), Phe27Val30hPYY(4-36), Phe27Ile31hPYY(4-36), Phe27Leu31hPYY(4-36), Phe27Ser32hPYY(4-36), Phe27Lys33hPYY(4-36), Phe27Asn34hPYY(4-36), Phe27Lys35hPYY(4-36), Phe27Thr36hPYY(4-36), Phe27Phe36hPYY(4-36), Gln29Ile30hPYY(4-36), Gln29Val30hPYY(4-36), Gln29Ile31hPYY(4-36), Gln29Leu31hPYY(4-36), Gln29Ser32, hPYY(4-36) Gln29Leu33hPYY(4-36), Gln29Asn34hPYY(4-36), Gln29Leu35hPYY(4-36), Gln29Thr36hPYY(4-36), Gln29Phe36hPYY(4-36), Ile30Ile31hPYY(4-36), Ile30Leu31hPYY(4-36), Ile30Ser32hPYY(4-36), Ile30Lys33hPYY(4-36), Ile30Asn34hPYY(4-36), Ile30Lys35hPYY(4-36), Ile30Thr36hPYY(4-36), Ile30Phe36hPYY(4-36), Val30Ile31hPYY(4-36), Val30Leu31hPYY(4-36), Val30Ser32hPYY(4-36), Val30Lys33hPYY(4-36), Val30Asn34hPYY(4-36), Val30Lys35hPYY(4-36), Val30Thr36hPYY(4-36), Val30Phe36hPYY(4-36), Ile31Ser32hPYY(4-36), Ile31Lys33hPYY(4-36), Ile31Asn34hPYY(4-36), Ile31Lys35hPYY(4-36), Ile31Thr36hPYY(4-36), Leu31Phe36hPYY(4-36), Leu31Phe36hPYY(4-36), Leu31Ser32hPYY(4-36), Val31Lys33hPYY(4-36), Leu31Asn34hPYY(4-36), Leu31Lys35hPYY(4-36), Leu31Thr36hPYY(4-36), Leu31Phe36hPYY(4-36), Ser32Lys33hPYY(4-36), Ser32Asn34hPYY(4-36), Ser32Lys35hPYY(4-36), Ser32Thr36hPYY(4-36), Ser32Phe36hPYY(4-36), Lys33Asn34hPYY(4-36), Lys33Lys35hPYY(4-36), Lys33Thr36hPYY(4-36), Lys33Phe36hPYY(4-36), Asn34Lys35hPYY(4-36), Asn34Phe36hPYY(4-36), Lys35Thr36hPYY(4-36), Lys35Phe36hPYY(4-36), Thr27hPYY(5-36), Phe27hPYY(5-36), Ile28hPYY(5-36), Val28hPYY(5-36), Gln29hPYY(5-36), Ile30hPYY(5-36), Val30hPYY(5-36), Ile31hPYY(5-36), Leu31hPYY(5-36), Ser32hPYY(5-36), Lys33hPYY(5-36), Asn34hPYY(5-36), Lys35hPYY(5-36), Thr36hPYY(5-36), Phe36hPYY(5-36), Lys25Thr27hPYY(5-36), Lys25Phe27hPYY(5-36), Lys25Ile28hPYY(5-36), Lys25Val28hPYY(5-36), Lys25Gln29hPYY(5-36), Lys25Ile30hPYY(5-36), Lys25Val30hPYY(5-36), Lys25Ile31hPYY(5-36), Lys25Leu31hPYY(5-36), Lys25Ser32hPYY(5-36), Lys25Lys33hPYY(5-36), Lys25Asn24hPYY(5-36), Lys25Lys35hPYY(5-36), Lys25Thr36hPYY(5-36), Lys25Phe36hPYY(5-36), Thr27Ile28hPYY(5-36), Thr27Val28hPYY(5-36), Thr27Gln29hPYY(5-36), Thr27Ile30hPYY(5-36), Thr27Val30hPYY(5-36), Thr27Ile31hPYY(5-36), Thr27Leu31hPYY(5-36), Thr27Ser32hPYY(5-36), Thr27Lys33hPYY(5-36), Thr27Asn34hPYY(5-36), Thr27Lys35hPYY(5-36), Thr27Thr36hPYY(5-36), Thr27Phe36hPYY(5-36), Phe27Ile28hPYY(5-36), Phe27Val28hPYY(5-36), Phe27Gln29hPYY(5-36), Phe27Ile30hPYY(5-36), Phe27Val30hPYY(5-36), Phe27Ile31hPYY(5-36), Phe27Leu31hPYY(5-36), Phe27Ser32hPYY(5-36), Phe27Lys33hPYY(5-36), Phe27Asn34hPYY(5-36), Phe27Lys35hPYY(5-36), Phe27Thr36hPYY(5-36), Phe27Phe36hPYY(5-36), Gln29Ile30hPYY(5-36), Gln29Val30hPYY(5-36), Gln29Ile31hPYY(5-36), Gln29Leu31hPYY(5-36), Gln29Ser32, hPYY(5-36) Gln29Leu33hPYY(5-36), Gln29Asn34hPYY(5-36), Gln29Leu35hPYY(5-36), Gln29Thr36hPYY(5-36), Gln29Phe36hPYY(5-36), Ile30Ile31hPYY(5-36), Ile30Leu31hPYY(5-36), Ile30Ser32hPYY(5-36), Ile30Lys33hPYY(5-36), Ile30Asn34hPYY(5-36), Ile30Lys35hPYY(5-36), Ile30Thr36hPYY(5-36), Ile30Phe36hPYY(5-36), Val30Ile31hPYY(5-36), Val30Leu31hPYY(5-36), Val30Ser32hPYY(5-36), Val30Lys33hPYY(5-36), Val30Asn34hPYY(5-36), Val30Lys35hPYY(5-36), Val30Thr36hPYY(5-36), Val30Phe36hPYY(5-36), Ile31Ser32hPYY(5-36), Ile31Lys33hPYY(5-36), Ile31Asn34hPYY(5-36), Ile31Lys35hPYY(5-36), Ile31Thr36hPYY(5-36), Leu31Phe36hPYY(5-36), Leu31Phe36hPYY(5-36), Leu31Ser32hPYY(5-36), Val31Lys33hPYY(5-36), Leu31Asn34hPYY(5-36), Leu31Lys35hPYY(5-36), Leu31Thr36hPYY(5-36), Leu31Phe36hPYY(5-36), Ser32Lys33hPYY(5-36), Ser32Asn34hPYY(5-36), Ser32Lys35hPYY(5-36), Ser32Thr36hPYY(5-36), Ser32Phe36hPYY(5-36), Lys33Asn34hPYY(5-36), Lys33Lys35hPYY(5-36), Lys33Thr36hPYY(5-36), Lys33Phe36hPYY(5-36), Asn34Lys35hPYY(5-36), Asn34Phe36hPYY(5-36), Lys35Thr36hPYY(5-36), or Lys35Phe36hPYY(5-36).
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4. A PPF polypeptide from about 34 to about 36 amino acids in length, comprising:
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an N-terminal fragment consisting essentially of 17 amino acids exhibiting at least 50% sequence identity to the first 17 amino acids of a native PYY; and a C-terminal fragment consisting essentially of 19 amino acids exhibiting at least 50% sequence identity to amino acids 18-36 of a native NPY, wherein the N-terminal and C-terminal fragments are covalently linked, and wherein one or two amino acid residues at the N-terminus of the PYY fragment may be deleted or absent; with the proviso that said PPF polypeptide does not include a modified natural amino acid and with the further proviso that said PPF polypeptide is not a native PPF polypeptide, PP, NPY(1-36), NPY(3-36), PYY(1-36), PYY(3-36), NPY(2-36), NPY(4-36), PYY(2-36), PYY(4-36), PP(2-36), PP(3-36), PP(4-36), Tyr1hPP, Lys4hPP, Asn7hPP, Arg19hPP, Tyr21hPP, Glu21hPP, Ala23hPP, Gln23hPP, Gln34hPP, Phe6Arg19hPP, Phe6Tyr21hPP, Phe6Glu21hPP, Phe6Ala23hPP, Phe6Gln23hPP, Pro13Ala14hPP, Ile31Gln34PP, Arg19Tyr20Tyr21Ser22Ala23hPP, Lys4Arg19Tyr20Tyr21Ser22Ala23hPP, Lys4Arg19Tyr20Tyr21Ser22Ala23hPP(2-36), Ala1NPY, Tyr1NPY, Ala2NPY, Leu2NPY, Phe2NPY, His2NPY, Ala3NPY, Ala4NPY, Ala6NPY, Tyr7pNPY, Ala7NPY, Ala9NPY, Ala1NPY, Ala11NPY, Gly12NPY, Ala13NPY, Gly14NPY, Ala15NPY, Ala16NPY, Ala17NPY, Gly18NPY, Ala19NPY, Lys19NPY, Ala20NPY, Ala21NPY, Ala22NPY, Gly23NPY, Ala24NPY, Trp24pNPY, Ala25NPY, Lys25NPY, Ala26NPY, Ala27NPY, Phe27NPY, Ala28NPY, Ala29NPY, Gln29NPY, Ala30NPY, Phe30NPY, Ala31NPY, Trp31pNPY, Ala32NPY. Trp32NPY, Ala33NPY, Lys33NPY, Ala34NPY, Pro34NPY, Leu34NPY, Ala35NPY, Lys35NPY, Ala36NPY, Phe36NPY, His36NPY, Glu4Pro34pNPY, Arg6Pro34pNPY, Phe6Pro34pNPY, Cys6Pro34pNPY, Asn6Pro34pNPY, Phe7Pro34pNPY, Arg7Pro34pNPY, Cys7Pro34pNPY, Asp7Pro34pNPY, Phe8Pro34pNPY, Arg8Pro34pNPY, Cys8Pro34pNPY, Asp8Pro34pNPY, Asn8Pro34pNPY, Pro11Pro34pNPY, Ser13Pro14pNPY, Trp24,31pNPY, Ala31Pro32pNPY, Cys31Pro34pNPY, Leu31Pro34NPY, Phe32Pro34pNPY, Ala21,25Pro34pNPY, Pro11Tyr13Pro14Pro34pNPY, Ahx(9-22)pNPY, Ahx(9-17)pNPY, des-AA(10-20)-Cys7,21Pro34-pNPY, des-AA(10-17)-pNPY, des-AA(10-17)-Cys2,27-pNPY, des-AA(10-17)-Ala7,21-pNPY, des-AA(10-17)-Cys7,21-pNPY, des-AA(10-17)-Glu7Lys21-pNPY, des-AA(10-17)Cys7,21Pro34pNPY, des-AA(10-17)Glu7Lys21Pro34pNPY, des-AA(10-17)Cys7,21Leu31Pro34pNPY, des-AA(11-17)Cys7,21Pro34pNPY, Pro34PYY, His34PYY, Lys25hPYY(5-36), Arg4hPYY(4-36), Gln4hPYY(4-36), Asn4hPYY(4-36), Lys25hPYY(4-36), Leu3hPYY(3-36), Val3hPYY(3-36), Lys25hPYY(3-36), Tyr1,36pPYY, Pro13Ala14hPYY, Leu31Pro34PYY, hPP(1-7)-pNPY, hPP(1-17)-pNPY, hPP(19-23)-pNPY, hPP(19-23)-Pro34pNPY, hPP(19-23)-His34pNPY, rPP(19-23)-pNPY, rPP(19-23)-Pro34pNPY, rPP(19-23)-His34pNPY, hPP(1-7)-pNPY, hPP(1-17)-pNPY, hPP(1-17)-His34pNPY, pNPY(1-7)-hPP, pNPY(1-7,19-23)-hPP, cPP(1-7)-pNPY(19-23)-hPP, cPP(1-7)-NPY(19-23)-His34hPP, hPP(1-17)-His34pNPY, hPP(19-23)-pNPY, hPP(19-23)-Pro34pNPY, hPP(19-23)-His34pNPY, rPP(19-23)-pNPY, rPP(19-23)-Pro34pNPY, rPP(19-23)-His34pNPY, pNPY(1-7)-hPP, pNPY(19-23)-hPP, pNPY(19-23)-Gln34hPP, pNPY(19-23)-His34hPP, pNPY(19-23)-Phe6Gln34hPP, pNPY(19-23)-Phe6His34hPP, pNPY(1-7,19-23)-hPP, pNPY(1-7,19-23)-Gln34hPP, cPP(20-23)-Pro34-pNPY, cPP(21-23)-Pro34-pNPY, cPP(22-23)-Pro34-pNPY, cPP(1-7)-Pro34-pNPY, cPP(20-23)-Pro34-pNPY, cPP(1-7,20-23)-Pro34-pNPY, cPP(1-7)-pNPY(19-23)-hPP, cPP(1-7)-pNPY(19-23)-His34hPP, or cPP(1-7)-gPP(19-23)-hPP, Thr27hPYY(3-36), Ile30hPYY(3-36), Ser32hPYY(3-36), Lys33hPYY(3-36), Asn34hPYY(3-36), Lys35hPYY(3-36), Thr36hPYY(3-36), Lys25Thr27hPYY(3-36), Lys25Ile30hPYY(3-36), Lys25Ser32hPYY(3-36), Lys25Lys33hPYY(3-36), Lys25Asn24hPYY(3-36), Lys25Lys35hPYY(3-36), Lys25Thr36hPYY(3-36), Thr27Ile28hPYY(3-36), Thr27Val28hPYY(3-36), Thr27Gln29hPYY(3-36), Thr27Ile30hPYY(3-36), Thr27Val30hPYY(3-36), Thr27Ile31hPYY(3-36), Thr27Leu31hPYY(3-36), Thr27Ser32hPYY(3-36), Thr27Lys33hPYY(3-36), Thr27Asn34hPYY(3-36), Thr27Lys35hPYY(3-36), Thr27Thr36hPYY(3-36), Thr27Phe36hPYY(3-36), Phe27Ile30hPYY(3-36), Phe27Ser32hPYY(3-36), Phe27Lys33hPYY(3-36), Phe27Asn34hPYY(3-36), Phe27Lys35hPYY(3-36), Phe27Thr36hPYY(3-36), Gln29Ile30hPYY(3-36), Gln29Ser32hPYY(3-36), Gln29Leu33hPYY(3-36), Gln29Asn34hPYY(3-36), Gln29Leu35hPYY(3-36), Gln29Thr36hPYY(3-36), Ile30Ile31hPYY(3-36), Ile30Leu31hPYY(3-36), Ile30Ser32hPYY(3-36), Ile30Lys33hPYY(3-36), Ile30Asn34hPYY(3-36), Ile30Lys35hPYY(3-36), Ile30Thr36hPYY(3-36), Ile30Phe36hPYY(3-36), Val30Ser32hPYY(3-36), Val30Lys33hPYY(3-36), Val30Asn34hPYY(3-36), Val30Lys35hPYY(3-36), Val30Thr36hPYY(3-36), Ile31Ser32hPYY(3-36), Ile31Lys33hPYY(3-36), Ile31Asn34hPYY(3-36), Ile31Lys35hPYY(3-36), Ile31Thr36hPYY(3-36), Ile31Phe36hPYY(3-36), Leu31Ser32hPYY(3-36), Leu31Lys33hPYY(3-36), Leu31Asn34hPYY(3-36), Leu31Lys35hPYY(3-36), Leu31Thr36hPYY(3-36), Ser32Lys33hPYY(3-36), Ser32Asn34hPYY(3-36), Ser32Lys35hPYY(3-36), Ser32Thr36hPYY(3-36), Ser32Phe36hPYY(3-36), Lys33Asn34hPYY(3-36), Lys33Lys35hPYY(3-36), Lys33Thr36hPYY(3-36), Lys33Phe36hPYY(3-36), Asn34Lys35hPYY(3-36), Asn34Phe36hPYY(3-36), Lys35Thr36hPYY(3-36), Lys35Phe36hPYY(3-36), Thr27hPYY(4-36), Phe27hPYY(4-36), Ile28hPYY(4-36), Val28hPYY(4-36), Gln29hPYY(4-36), Ile30hPYY(4-36), Val30hPYY(4-36), Ile31hPYY(4-36), Leu31hPYY(4-36), Ser32hPYY(4-36), Lys33hPYY(4-36), Asn34hPYY(4-36), Lys35hPYY(4-36), Thr36hPYY(4-36), Phe36hPYY(4-36), Lys25Thr27hPYY(4-36), Lys25Phe27hPYY(4-36), Lys25Ile28hPYY(4-36), Lys25Val28hPYY(4-36), Lys25Gln29hPYY(4-36), Lys25Ile30hPYY(4-36), Lys25Val30hPYY(4-36), Lys25Ile31hPYY(4-36), Lys25Leu31hPYY(4-36), Lys25Ser32hPYY(4-36), Lys25Lys33hPYY(4-36), Lys25Asn24hPYY(4-36), Lys25Lys35hPYY(4-36), Lys25Thr36hPYY(4-36), Lys25Phe36hPYY(4-36), Thr27Ile28hPYY(4-36), Thr27Val28hPYY(4-36), Thr27Gln29hPYY(4-36), Thr27Ile30hPYY(4-36), Thr27Val30hPYY(4-36), Thr27Ile31hPYY(4-36), Thr27Leu31hPYY(4-36), Thr27Ser32hPYY(4-36), Thr27Lys33hPYY(4-36), Thr27Asn34hPYY(4-36), Thr27Lys35hPYY(4-36), Thr27Thr36hPYY(4-36), Thr27Phe36hPYY(4-36), Phe27Ile28hPYY(4-36), Phe27Val28hPYY(4-36), Phe27Gln29hPYY(4-36), Phe27Ile30hPYY(4-36), Phe27Val30hPYY(4-36), Phe27Ile31hPYY(4-36), Phe27Leu31hPYY(4-36), Phe27Ser32hPYY(4-36), Phe27Lys33hPYY(4-36), Phe27Asn34hPYY(4-36), Phe27Lys35hPYY(4-36), Phe27Thr36hPYY(4-36), Phe27Phe36hPYY(4-36), Gln29Ile30hPYY(4-36), Gln29Val30hPYY(4-36), Gln29Ile31hPYY(4-36), Gln29Leu31hPYY(4-36), Gln29Ser32, hPYY(4-36) Gln29Leu33hPYY(4-36), Gln29Asn34hPYY(4-36), Gln29Leu35hPYY(4-36), Gln29Thr36hPYY(4-36), Gln29Phe36hPYY(4-36), Ile30Ile31hPYY(4-36), Ile30Leu31hPYY(4-36), Ile30Ser32hPYY(4-36), Ile30Lys33hPYY(4-36), Ile30Asn34hPYY(4-36), Ile30Lys35hPYY(4-36), Ile30Thr36hPYY(4-36), Ile30Phe36hPYY(4-36), Val30Ile31hPYY(4-36), Val30Leu31hPYY(4-36), Val30Ser32hPYY(4-36), Val30Lys33hPYY(4-36), Val30Asn34hPYY(4-36), Val30Lys35hPYY(4-36), Val30Thr36hPYY(4-36), Val30Phe36hPYY(4-36), Ile31Ser32hPYY(4-36), Ile31Lys33hPYY(4-36), Ile31Asn34hPYY(4-36), Ile31Lys35hPYY(4-36), Ile31Thr36hPYY(4-36), Leu31Phe36hPYY(4-36), Leu31Phe36hPYY(4-36), Leu31Ser32hPYY(4-36), Val31Lys33hPYY(4-36), Leu31Asn34hPYY(4-36), Leu31Lys35hPYY(4-36), Leu31Thr36hPYY(4-36), Leu31Phe36hPYY(4-36), Ser32Lys33hPYY(4-36), Ser32Asn34hPYY(4-36), Ser32Lys35hPYY(4-36), Ser32Thr36hPYY(4-36), Ser32Phe36hPYY(4-36), Lys33Asn34hPYY(4-36), Lys33Lys35hPYY(4-36), Lys33Thr36hPYY(4-36), Lys33Phe36hPYY(4-36), Asn34Lys35hPYY(4-36), Asn34Phe36hPYY(4-36), Lys35Thr36hPYY(4-36), Lys35Phe36hPYY(4-36), Thr27hPYY(5-36), Phe27hPYY(5-36), Ile28hPYY(5-36), Val28hPYY(5-36), Gln29hPYY(5-36), Ile30hPYY(5-36), Val30hPYY(5-36), Ile31hPYY(5-36), Leu31hPYY(5-36), Ser32hPYY(5-36), Lys33hPYY(5-36), Asn34hPYY(5-36), Lys35hPYY(5-36), Thr36hPYY(5-36), Phe36hPYY(5-36), Lys25Thr27hPYY(5-36), Lys25Phe27hPYY(5-36), Lys25Ile28hPYY(5-36), Lys25Val28hPYY(5-36), Lys25Gln29hPYY(5-36), Lys25Ile30hPYY(5-36), Lys25Val30hPYY(5-36), Lys25Ile31hPYY(5-36), Lys25Leu31hPYY(5-36), Lys25Ser32hPYY(5-36), Lys25Lys33hPYY(5-36), Lys25Asn24hPYY(5-36), Lys25Lys35hPYY(5-36), Lys25Thr36hPYY(5-36), Lys25Phe36hPYY(5-36), Thr27Ile28hPYY(5-36), Thr27Val28hPYY(5-36), Thr27Gln29hPYY(5-36), Thr27Ile30hPYY(5-36), Thr27Val30hPYY(5-36), Thr27Ile31hPYY(5-36), Thr27Leu31hPYY(5-36), Thr27Ser32hPYY(5-36), Thr27Lys33hPYY(5-36), Thr27Asn34hPYY(5-36), Thr27Lys35hPYY(5-36), Thr27Thr36hPYY(5-36), Thr27Phe36hPYY(5-36), Phe27Ile28hPYY(5-36), Phe27Val28hPYY(5-36), Phe27Gln29hPYY(5-36), Phe27Ile30hPYY(5-36), Phe27Val30hPYY(5-36), Phe27Ile31hPYY(5-36), Phe27Leu31hPYY(5-36), Phe27Ser32hPYY(5-36), Phe27Lys33hPYY(5-36), Phe27Asn34hPYY(5-36), Phe27Lys35hPYY(5-36), Phe27Thr36hPYY(5-36), Phe27Phe36hPYY(5-36), Gln29Ile30hPYY(5-36), Gln29Val30hPYY(5-36), Gln29Ile31hPYY(5-36), Gln29Leu31hPYY(5-36), Gln29Ser32, hPYY(5-36) Gln29Leu33hPYY(5-36), Gln29Asn34hPYY(5-36), Gln29Leu35hPYY(5-36), Gln29Thr36hPYY(5-36), Gln29Phe36hPYY(5-36), Ile30Ile31hPYY(5-36), Ile30Leu31hPYY(5-36), Ile30Ser32hPYY(5-36), Ile30Lys33hPYY(5-36), Ile30Asn34hPYY(5-36), Ile30Lys35hPYY(5-36), Ile30Thr36hPYY(5-36), Ile30Phe36hPYY(5-36), Val30Ile31hPYY(5-36), Val30Leu31hPYY(5-36), Val30Ser32hPYY(5-36), Val30Lys33hPYY(5-36), Val30Asn34hPYY(5-36), Val30Lys35hPYY(5-36), Val30Thr36hPYY(5-36), Val30Phe36hPYY(5-36), Ile31Ser32hPYY(5-36), Ile31Lys33hPYY(5-36), Ile31Asn34hPYY(5-36), Ile31Lys35hPYY(5-36), Ile31Thr36hPYY(5-36), Leu31Phe36hPYY(5-36), Leu31Phe36hPYY(5-36), Leu31Ser32hPYY(5-36), Val31Lys33hPYY(5-36), Leu31Asn34hPYY(5-36), Leu31Lys35hPYY(5-36), Leu31Thr36hPYY(5-36), Leu31Phe36hPYY(5-36), Ser32Lys33hPYY(5-36), Ser32Asn34hPYY(5-36), Ser32Lys35hPYY(5-36), Ser32Thr36hPYY(5-36), Ser32Phe36hPYY(5-36), Lys33Asn34hPYY(5-36), Lys33Lys35hPYY(5-36), Lys33Thr36hPYY(5-36), Lys33Phe36hPYY(5-36), Asn34Lys35hPYY(5-36), Asn34Phe36hPYY(5-36), Lys35Thr36hPYY(5-36), or Lys35Phe36hPYY(5-36).
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5. (canceled)
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17-29. -29. (canceled)
- 30. A method for altering body composition of a subject, comprising administering to the subject a PPF polypeptide, wherein the PPF polypeptide alters the fat to lean ratio, thereby altering body composition.
- 45. A method for preferentially lowering plasma triglyceride levels in a subject, comprising administering to the subject an amount of a PPF polypeptide effective to lower plasma triglyceride levels, wherein cholesterol levels are lowered to a lesser extent.
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50. A method for reducing body fat or body fat gain in a subject while maintaining or increasing lean body mass, comprising administering to the subject an amount of a PPF polypeptide effective to reduce body fat or body fat gain while maintaining or increasing lean body mass.
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51. A method of reducing central body fat in a subject, comprising administering to the subject an amount of a PPF polypeptide effective to reduce central body fat and preserve or increase lean body mass.
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52. A method of increasing fatty acid β
- -oxidation while preserving or increasing lean body mass in a subject comprising administering to the subject an amount of a PPF polypeptide effective to increase fatty acid β
-oxidation while preserving or increasing lean body mass.
- -oxidation while preserving or increasing lean body mass in a subject comprising administering to the subject an amount of a PPF polypeptide effective to increase fatty acid β
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53. A method of treating nonalcoholic steatohepatitis or lipodystrophy in a subject comprising administering to the subject an amount of a PPF polypeptide effective to treat nonalcoholic steatohepatitis or lipodystrophy.
Specification