Peptide agonists of GLP-1 activity

• US 6,528,486 B1
• Filed: 07/12/2000
• Issued: 03/04/2003
• Est. Priority Date: 07/12/1999
• Status: Expired

• Current Assignee: ZP Holding SPV K/S (Zealand Pharma A/S)
• Original Assignee: Zealand Pharma A/S
• Inventors: Mikkelsen, Jens Damsgaard, Neve, Søren, Larsen, Bjarne Due
• Primary Examiner(s): Spector, Lorraine
• Assistant Examiner(s): Jiang, Dong
• Application Number:
  US09/614,847
• Time in Patent Office: 965 Days
• Field of Search: 514/12, 514/2, 530/300, 530/303
• US Class Current: 514/6.8
• 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: A61K 47/62 the modifying agent being a protein, peptide or polyamino acid
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: C07K 14/57563 Vasoactive intestinal peptide [VIP]; Related peptides
• CPC Class Codes: C07K 14/605 Glucagons

Abstract

The present invention relates to novel peptide conjugates which have increased stability and are useful in the treatment of excess levels of blood glucose.

Claims

1. A peptide consisting of any one of the following sequences:

a) H-His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-Ala-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Ser-(Lys)₆-NH₂ (des-Pro³⁶-exendin-4(1-39)-Lys₆-NH₂) (SEQ ID NO;

93),

b) H-Lys₆-His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-Ala-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Ser-(Lys)₆-NH₂ (H-Lys₆-des Pro³⁶exendin-4(1-39)-Lys₆-NH₂) (SEQ ID NO;

     149),

c) H-His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-Ala-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Ser-NH₂ (H-des Pro³⁶,Pro³⁷,Pro³⁸exendin-4(1-39)-NH₂) (SEQ ID NO;

     132),

d) H-Lys-Lys-Lys-Lys-Lys-Lys-His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-Ala-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Ser-NH₂ (H-(Lys)₆-des Pro³⁶,Pro³⁷,Pro³⁸exendin-4(1-39)-NH₂), (SEQ ID NO;

     134),

e) H-Asn-Glu-Glu-Glu-Glu-Glu-His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-Ala-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Ser-NH₂ (H-Asn-(Glu)₅-des Pro³⁶,Pro³⁷, Pro³⁸exendin-4(1-39)-NH²) (SEQ ID NO;

     137),

f) H-His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-Ala-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Ser-(Lys)₆-NH₂ (des Pro³⁶, Pro³⁷,Pro³⁸exendin-4(1-39)-(Lys)₆-NH₂) (SEQ ID NO;

     133),

g) H-(Lys)₆-His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-Ala-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Ser-(Lys)₆-NH₂ (H-(Lys)₆-des Pro³⁶,Pro³⁷,Pro³⁸exendin-4(1-39)-(Lys)₆-NH₂) (SEQ ID NO;

     135),

h) H-Asp-Glu-Glu-Glu-Glu-Glu-His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-Ala-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Ser-(Lys)₆-NH₂ (H-Asn-(Glu)₅-des Pro³⁶,Pro³⁷,Pro³⁸exendin-4(1-39)-(Lys)₆-NH₂) (SEQ ID NO;

     136);

or a pharmaceutically acceptable salt thereof.

2. A composition comprising the peptide of claim 1 and a physiologically acceptable carrier.