Glucagon-like peptide-2 analogs

• US 8,933,039 B2
• Filed: 06/15/2010
• Issued: 01/13/2015
• Est. Priority Date: 04/14/1995
• Status: Expired due to Fees

• Current Assignee: 1149336 Ontario Inc., NPS Pharmaceuticals Incorporated (Shire plc)
• Original Assignee: 1149336 Ontario Inc., NPS Pharmaceuticals Incorporated (Shire plc)
• Inventors: Drucker, Daniel J, Crivici, Anna E., Sumner-Smith, Martin
• Primary Examiner(s): GUDIBANDE, SATYANARAYAN R
• Application Number:
  US12/816,312
• Publication Number:
  US 20110009320A1
• Time in Patent Office: 1,673 Days
• Field of Search: None
• US Class Current: 514/21.3
• 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. An intestinotrophic GLP-2 analog, comprising SEQ ID NO:

2, wherein

position 2 of SEQ ID NO;

2 consists of an amino acid other than Ala,

positions 5-9, 11-18, and 21-23 of SEQ ID NO;

2 are unmodified,

position 1 of SEQ ID NO;

2 optionally consists of an amino acid other than His;

position 3 of SEQ ID NO;

2 optionally consists of an amino acid other than Asp;

position 4 of SEQ ID NO;

2 optionally consists of an amino acid other than Gly;

position 10 of SEQ ID NO;

2 optionally consists of an amino acid other than Met;

position 19 of SEQ ID NO;

2 optionally consists of an amino acid other than Ala;

position 20 of SEQ ID NO;

2 optionally consists of an amino acid other than Arg; and

position 24 of SEQ ID NO;

2 optionally consists of an amino acid other than Asn.

2. A pharmaceutical composition comprising the GLP-2 analog of claim 1, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

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

4. The GLP-2 analog of claim 1, wherein the amino acid at position 2 is one of the following:

D-Ala, Gly, Val, t-Butyl-Gly, Asp, Glu, Phe, His, Ile, Lys, Met, Asn, Pro, Gln, Ser, Thr, Tyr, Pen, β

-Ala, α

-Abu, Nval, PhGly, or Aib.

5. The GLP-2 analog of claim 1, wherein the amino acid at position 3 is Glu or Ala.

6. The GLP-2 analog of claim 1, wherein the amino acid at position 4 is Ala.

7. The GLP-2 analog of claim 1, wherein the amino acid at position 10 is one of the following:

Val, Ile, Asn, Glu, Gln, Tyr, Phe, Leu, Nle, Ala, Ser, or Gly.

8. The GLP-2 analog of claim 1, wherein the amino acid at position 19 is Thr.

9. The GLP-2 analog of claim 1, wherein the amino acid at position 20 is Lys or Ala.

10. The GLP-2 analog of claim 1, wherein the amino acid at position 24 is Ala.

11. The GLP-2 analog of claim 1 wherein the amino acid at position 2 is Gly.