PANCREATIC POLYPEPTIDE FAMILY MOTIFS, POLYPEPTIDES AND METHODS COMPRISING THE SAME

1 . A method for treating diabetes, obesity, a gastrointestinal disorder, an eating disorder, insulin-resistance syndrome, a cardiovascular disease, nonalcoholic steatohepatitis, or lipodystrophy in a mammal in need thereof comprising administering to the mammal a therapeutically effective amount of a PPF polypeptide to treat the obesity, diabetes, gastrointestinal disorder, eating disorder, insulin-resistance syndrome, cardiovascular disease, nonalcoholic steatohepatitis, or lipodystrophy.

2 . The method of claim 1 for treating diabetes in the mammal in need thereof.

3 . The method of claim 2 , wherein the diabetes is Type 1 diabetes.

4 . The method of claim 2 , wherein the diabetes is Type 2 diabetes.

5 . The method of claim 1 for treating obesity in the mammal in need thereof.

6 . The method of claim 1 , wherein the PPF polypeptide comprises an amino acid sequence of Formula (VII) (SEQ ID NO: 482):

Xaa 1 Xaa 2 Pro Xaa 4 Pro Xaa 6 His Pro Xaa 9 Xaa 10

Xaa 11 Xaa 12 Xaa 13 Xaa 14 Xaa 15 Xaa 16 Xaa 17 Ala

Xaa 19 Tyr Xaa 21 Xaa 22 Xaa 23 Leu Xaa 25 Xaa 26 Xaa 27

Xaa 28 Xaa 29 Xaa 30 Xaa 31 Thr Arg Gln Arg Tyr

wherein:

Xaa 1 is Tyr or absent;

Xaa 2 is Ile, Pro, or absent;

Xaa 4 is Lys, BH-modified Lys, Ala, Ser, or Arg;

Xaa 6 is Glu, Gln, Ala, Asn, Asp, or Val;

Xaa 9 is Gly or Ala;

Xaa 10 is Glu, Ala, Asp, Asn, Gln, Gly, Pro, or Aib;

Xaa 11 is Glu, Ala, Asp, Asn, Gln, Gly, Pro, or Aib;

Xaa 12 is Ala or Pro;

Xaa 13 is Ser or Pro;

Xaa 14 is Pro, Ala, or Ser;

Xaa 15 is Glu, Ala, Asp, Asn, Gln, Gly, Pro, or Aib;

Xaa 16 is Glu or Asp;

Xaa 17 is Leu or Ile;

Xaa 19 is Arg, Lys, BH-modified Lys, Gln, or N(Me)Ala;

Xaa 21 is Tyr, Ala, Phe, Lys, or BH-modified Lys;

Xaa 22 is Ala or Ser;

Xaa 23 is Ser, Ala, or Asp;

Xaa 25 is Arg, Lys or BH-modified Lys;

Xaa 26 is His, Ala, or Arg;

Xaa 27 is Tyr, or Phe;

Xaa 28 is Leu or Ile;

Xaa 29 is Asn, or Gln;

Xaa 30 is Leu or Met; and

Xaa 31 is Val, Ile, or Leu.

7 . The method of claim 1 , wherein the PPF polypeptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 266, 437, 438, 439, 442, 462, 469, 470, 471, and 472.

8 . The method of claim 1 , wherein the PPF polypeptide further comprises an N-terminal cap.

9 . The method of claim 1 , wherein the PPF polypeptide is linked to one or more water-soluble polymers.

10 . The method of claim 9 , wherein the one or more water-soluble polymers are selected from at least one of the group consisting of polyethylene glycol and a fatty acid molecule, wherein the polymer is linked to the N- or C-terminus of the polypeptide, or the side chain of a lysine or serine amino acid residue within the sequence of the polypeptide.

11 . A method for reducing food intake, reducing nutrient availability, causing weight loss, affecting body composition, altering body energy content or energy expenditure, or improving lipid profile in a mammal in need thereof comprising administering to the mammal a therapeutically effective amount of a PPF polypeptide to reduce food intake, reduce nutrient availability, cause weight loss, affect body composition, alter body energy content or energy expenditure, or improve lipid profile.

12 . The method of claim 11 , wherein the method for affecting body composition is a method for reducing body weight.

13 . The method of claim 11 , wherein the PPF polypeptide comprises an amino acid sequence of Formula (VII) (SEQ ID NO: 482):

Xaa 1 Xaa 2 Pro Xaa 4 Pro Xaa 6 His Pro Xaa 9 Xaa 10

Xaa 11 Xaa 12 Xaa 13 Xaa 14 Xaa 15 Xaa 16 Xaa 17 Ala

Xaa 19 Tyr Xaa 21 Xaa 22 Xaa 23 Leu Xaa 25 Xaa 26 Xaa 27

Xaa 28 Xaa 29 Xaa 30 Xaa 31 Thr Arg Gln Arg Tyr

wherein:

Xaa 1 is Tyr or absent;

Xaa 2 is Ile, Pro, or absent;

Xaa 4 is Lys, BH-modified Lys, Ala, Ser, or Arg;

Xaa 6 is Glu, Gln, Ala, Asn, Asp, or Val;

Xaa 9 is Gly or Ala;

Xaa 10 is Glu, Ala, Asp, Asn, Gln, Gly, Pro, or Aib;

Xaa 11 is Glu, Ala, Asp, Asn, Gln, Gly, Pro, or Aib;

Xaa 12 is Ala or Pro;

Xaa 13 is Ser or Pro;

Xaa 14 is Pro, Ala, or Ser;

Xaa 15 is Glu, Ala, Asp, Asn, Gln, Gly, Pro, or Aib;

Xaa 16 is Glu or Asp;

Xaa 17 is Leu or Ile;

Xaa 19 is Arg, Lys, BH-modified Lys, Gln, or N(Me)Ala;

Xaa 21 is Tyr, Ala, Phe, Lys, or BH-modified Lys;

Xaa 22 is Ala or Ser;

Xaa 23 is Ser, Ala, or Asp;

Xaa 25 is Arg, Lys or BH-modified Lys;

Xaa 26 is His, Ala, or Arg;

Xaa 27 is Tyr, or Phe;

Xaa 28 is Leu or Ile;

Xaa 29 is Asn, or Gln;

Xaa 30 is Leu or Met; and

Xaa 31 is Val, Ile, or Leu.

14 . The method of claim 11 , wherein the PPF polypeptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 266, 437, 438, 439, 442, 462, 469, 470, 471, and 472.

15 . The method of claim 11 , wherein the PPF polypeptide further comprises an N-terminal cap.

16 . The method of claim 1 , wherein the PPF polypeptide is linked to one or more water-soluble polymers.

17 . The method of claim 16 , wherein the one or more water-soluble polymers are selected from at least one of the group consisting of polyethylene glycol and a fatty acid molecule, wherein the polymer is linked to the N- or C-terminus of the polypeptide, or the side chain of a lysine or serine amino acid residue within the sequence of the polypeptide.