GLUCAGON-LIKE PEPTIDE-2 ANALOGS

• US 20110009320A1
• Filed: 06/15/2010
• Published: 01/13/2011
• Est. Priority Date: 04/14/1995
• Status: Active Grant

• Current Assignee: NPS Pharmaceuticals Incorporated (Shire plc)
• Original Assignee: NPS Pharmaceuticals Incorporated (Shire plc)
• Inventors: Sumner-Smith, Martin, Crivici, Anna E., Drucker, Daniel J.
• Granted Patent: US 8,933,039 B2
• Time in Patent Office: Days
• US Class Current: 514/11.7
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 38/26 Glucagons
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: C07K 14/605 Glucagons
• CPC Class Codes: G01N 33/4833 of solid biological material, e.g. tissue samples, cell cultures tissue in vivo A61B5/00; cell suspensions G01N33/48735

Abstract

Analogs of glucagon-like peptide 2, a product of glucagon gene expression, have been identified as intestinal tissue growth factors. Their formulation as pharmaceutical, and therapeutic use in treating disorders of the small bowel, are described.

Claims

1-29. -29. (canceled)

30. A GLP-2 analog of SEQ ID NO:

2 having intestinotrophic activity, wherein said analog comprises at least one of the following;

an amino acid other than His in place of His¹;

an amino acid other than Ala in place of Ala²;

an amino acid other than Asp in place of Asp³;

an amino acid other than Gly in place of Gly⁴;

an amino acid other than Met in place of Met¹⁰;

an amino acid other than Ala in place of Ala¹⁹;

an amino acid other than Arg in place of Arg²⁰;

or

an amino acid other than Asn in place of Asn²⁴.

31. A pharmaceutical composition comprising the GLP-2 analog of claim 30, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

32. The GLP-2 analog of claim 30, wherein the amino acid at position 1 is Tyr or Ala.

33. The GLP-2 analog of claim 30, wherein the amino acid at position 2 is one of the following:

D-Ala, Gly, Val, tBuGly, Asp, Glu, Phe, His, Ile, Lys, Met, Asn, Pro, Gln, Ser, Thr, Val, Tyr, Pen, bAla, aAbu, Nval, PhGly, or Aib.

34. The GLP-2 analog of claim 30, wherein the amino acid at position 3 is Glu or Ala.

35. The GLP-2 analog of claim 30, wherein the amino acid at position 4 is Ala.

36. The GLP-2 analog of claim 30, wherein the amino acid at position 10 is an oxidatively stable Met replacement amino acid.

37. The GLP-2 analog of claim 36, wherein the amino acid at position 10 is Val, Ile, Asn, Glx, Tyr, Phe, Leu, Nle, Ala, Ser, or Gly.

38. The GLP-2 analog of claim 30, wherein the amino acid at position 19 is Thr.

39. The GLP-2 analog of claim 30, wherein the amino acid at position 20 is Lys or Ala.

40. The GLP-2 analog of claim 30, wherein the amino acid at position 24 is Ala.

41. A GLP-2 analog of SEQ ID NO:

2 having intestinotrophic activity, wherein said analog comprises at least one of the following;

an amino acid other than Ser in place of Ser⁵;

an amino acid other than Ser in place of Ser⁷;

an amino acid other than Asn in place of Asn¹⁶;

an amino acid other than Leu in place of Leu¹⁷;

an amino acid other than Ala in place of Ala¹⁸;

an amino acid other than Trp in place of Trp²⁵;

an amino acid other than Lys in place of Lys³⁰;

or

an amino acid other than Asp in place of Asp³³.

42. A pharmaceutical composition comprising the GLP-2 analog of claim 41, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

43. The GLP-2 analog of claim 41, wherein the amino acid at position 5 is Ala.

44. The GLP-2 analog of claim 41, wherein the amino acid at position 7 is Ala.

45. The GLP-2 analog of claim 41, wherein the amino acid at position 16 is Ser.

46. The GLP-2 analog of claim 41, wherein the amino acid at position 17 is Arg.

47. The GLP-2 analog of claim 41, wherein the amino acid at position 18 is Arg.

48. The GLP-2 analog of claim 41, wherein the amino acid at position 25 is Phe.

49. The GLP-2 analog of claim 41, wherein the amino acid at position 30 is Arg.

50. The GLP-2 analog of claim 41, wherein the amino acid at position 33 is Glu.