THERAPEUTIC PEPTIDES

• US 20160108098A1
• Filed: 04/30/2014
• Published: 04/21/2016
• Est. Priority Date: 05/02/2013
• Status: Abandoned Application

• Current Assignee: GlaxoSmithKline Intellectual Property Development Limited (Glaxosmithkline Holdings Ltd.)
• Original Assignee: GlaxoSmithKline Intellectual Property Development Limited (Glaxosmithkline Holdings Ltd.)
• Inventors: DOCK, Steven Thomas, WU, Yulin, Srivastava, Ved P, HUNTER, Robert Neil III, CARPENTER, Andrew James
• Application Number:
  US14/888,085
• Publication Number:
  US 20160108098A1
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 38/1709 from mammals
• CPC Class Codes: A61K 38/22 Hormones derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin A61K38/33, e.g. corticotropin A61K38/35
• CPC Class Codes: A61K 38/26 Glucagons
• CPC Class Codes: A61K 38/55 Protease inhibitors
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 14/47 from mammals
• CPC Class Codes: C07K 14/57545 Neuropeptide Y

Abstract

The present invention relates to novel analogs of PYY that have an improved therapeutic profile when compared to native human PYY. These novel PYY analogs are useful in the treatment of obesity, diabetes, and other disorders.

Claims

1-16. -16. (canceled)

17. A polypeptide comprising the amino acid sequence:

20. The polypeptide of claim 17 which comprises the amino acid sequence:

21. The polypeptide of claim 17 which consists of the amino acid sequence:

25. A pharmaceutical combination comprising a polypeptide according to claim 17 and an exendin-4 or GLP-1.

26. A pharmaceutical composition comprising a polypeptide according to claim 17 and a pharmaceutically acceptable carrier.

27. A method of treating a metabolic disorder such as obesity or Type 2 diabetes mellitus in a human subject, said method comprising administering a polypeptide or pharmaceutical combination of claim 17 to a subject in need thereof.

28. Use of a polypeptide or pharmaceutical composition or combination of claim 17 in the preparation of a medicament for use in the treatment of a metabolic disorder such as obesity or Type 2 diabetes mellitus.

29. A polypeptide or pharmaceutical composition or combination according to claim 17 for use in the treatment of a metabolic disorder such as obesity or Type 2 diabetes mellitus.

30. A nucleic acid molecule encoding a polypeptide sequence according to claim 17.

31. An expression vector comprising a nucleic acid molecule according to claim 30.

32. A host cell containing an expression vector according to claim 31.

18. A polypeptide consisting of the amino acid sequence:

ProLysProGluXaa₁ProGlyXaa₂AspAlaSerXaa₃GluGlu Xaa₄Xaa₅ Xaa₆TyrTyrAlaXaa₇LeuArg Xaa₈Tyr Xaa₉ AsnTrp Xaa₁₀ThrArgGlnArgTyr-NH₂ (SEQ ID NO;

2) or a salt thereof, wherein;

Xaa₁ is Ala, His, or Ser;

Xaa₂ is Glu or Lys;

Xaa₃ is Pro or Ala;

Xaa₄ is Leu or Trp;

Xaa₅ is Asn, Ala, or Thr;

Xaa₆ is Arg or Lys;

Xaa₇ is Ser, Asp, or Ala;

Xaa₈ is His or Lys;

Xaa₉ is Leu or Ile; and

Xaa₁₀ is Val or Leu.

19. The polypeptide of claim 18 which is selected from the group consisting of:

22. The polypeptide of claim 18 which consists of the amino acid sequence:

23. A salt form of the polypeptide of claim 22.

24. A salt form of the polypeptide according to claim 23, wherein said salt is the acetate salt.