Peptide conjugates of GLP-1 receptor agonists and gastrin and their use

• US 10,406,207 B2
• Filed: 12/16/2016
• Issued: 09/10/2019
• Est. Priority Date: 04/27/2010
• Status: Active Grant

• Current Assignee: Zealand Pharma A/S
• Original Assignee: Zealand Pharma A/S
• Inventors: Neerup, Trine Skovlund Ryge, Osterlund, Torben, Tolborg, Jakob Lind, Fosgerau, Keld, Martensson, Ulrika, Brorson, Marianne, Rolsted, Kamilla
• Primary Examiner(s): Heard, Thomas S
• Application Number:
  US15/381,993
• Publication Number:
  US 20170281709A1
• Time in Patent Office: 998 Days
• 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 38/22 Hormones derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin A61K38/33, e.g. corticotropin A61K38/35
• CPC Class Codes: A61K 38/2207 Gastrins; Cholecystokinins [CCK]
• CPC Class Codes: A61K 38/26 Glucagons
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/60 the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/18 for pancreatic disorders, e.g. pancreatic enzymes
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/50 for increasing or potentiating the activity of insulin
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/12 Antihypertensives
• CPC Class Codes: A61P 9/14 Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
• CPC Class Codes: C07K 14/463 : from amphibians
• CPC Class Codes: C07K 14/575 : Hormones derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin C07K14/665, e.g. corticotropin C07K14/695
• CPC Class Codes: C07K 14/57563 : Vasoactive intestinal peptide [VIP]; Related peptides
• CPC Class Codes: C07K 14/595 : Gastrins; Cholecystokinins [CCK]
• CPC Class Codes: C07K 14/605 : Glucagons

Abstract

The present invention relates, inter alia, to certain peptide conjugates, and to the use of the conjugates in the treatment of a variety of diseases or disorders, including diabetes (type 1 and/or type 2) and diabetes related diseases or disorders.

Claims

1. A peptide conjugate or pharmaceutically acceptable salt thereof, wherein the peptide conjugate has the sequence:

Exendin-4(1-39)-Peg3-Peg3-[Gln1,Leu15]Gastrin17, (SEQ ID NO;

     1)

Exendin-4(1-39)-[Gln1,Leu15]Gastrin17, (SEQ ID NO;

     2)

Exendin-4(1-39)-K-[Gln1,Leu15]Gastrin17, (SEQ ID NO;

     3)

Exendin-4(1-39)-AAA-[Gln1,Leu15]Gastrin17, (SEQ ID NO;

     4)

Exendin-4(1-39)-SKK-[Gln1,Leu15]Gastrin17, (SEQ ID NO;

     5)

Exendin-4(1-39)-Peg3-SKK-[Gln1,Leu15]Gastrin17, (SEQ ID NO;

     6)

Exendin-4(1-39)-8Aoc-SKK-[Gln1,Leu15]Gastrin17, (SEQ ID NO;

     7)

Exendin-4(1-39)-DBF-SKK-[Gln1,Leu15]Gastrin17, (SEQ ID NO;

     8)

Exendin-4(1-39)-8Aoc-8Aoc-[Gln1,Leu15]Gastrin17, (SEQ ID NO;

     9)

Exendin-4(1-28-[Gln1,Leu15]Gastrin17, (SEQ ID NO;

     19)

Exendin-4(1-28)-K-[Gln1,Leu15]Gastrin17, (SEQ ID NO;

     20)

Exendin-4(1-28)-AAA-[Gln1,Leu15]Gastrin17, (SEQ ID NO;

     21)

Exendin-4(1-28)-SKK-[Gln1,Leu15]Gastrin17, (SEQ ID NO;

     22)

Exendin-4(1-28)-Peg3-SKK-[Gln1,Leu15]Gastrin17, (SEQ ID NO;

     23)

Exendin-4(1-28)-Peg3-Peg3-[Gln1,Leu15]Gastrin17, (SEQ ID NO;

     24)

Exendin-4(1-28)-8Aoc-SKK-[Gln1,Leu15]Gastrin17, (SEQ ID NO;

     25)

Exendin-4(1-28)-DBF-SKK-[Gln1,Leu15]Gastrin17, (SEQ ID NO;

     26)

Exendin-4(1-28)-8Aoc-8Aoc-[Gln1,Leu15]Gastrin17, (SEQ ID NO;

     27).

2. A pharmaceutical composition comprising a peptide conjugate, or pharmaceutically acceptable salt thereof, according to claim 1, in combination with one or more peptide conjugates or pharmaceutically acceptable salt thereof together with a pharmaceutically acceptable carrier, excipient or vehicle.

3. A device comprising at least one peptide conjugate, or pharmaceutically acceptable salt thereof, according to claim 1, for delivery of the peptide conjugate to a subject.

4. A kit comprising at least one peptide conjugate, or pharmaceutically acceptable salt thereof, according to claim 1, further comprising packaging or instructions for use.