Insulin receptor partial agonists

• US 10,183,981 B2
• Filed: 06/13/2018
• Issued: 01/22/2019
• Est. Priority Date: 11/21/2014
• Status: Active Grant

• Current Assignee: Merck Sharp & Dohme LLC (Merck & Co., Inc.)
• Original Assignee: Merck Sharp & Dohme Corporation (Merck & Co., Inc.)
• Inventors: Lin, Songnian, Yan, Lin, Huo, Pei, Pissarnitski, Dmitri, Feng, Danqing, Nargund, Ravi, Zhu, Yuping, Kekec, Ahmet, Madsen-Duggan, Christina B., Shi, Zhi-Cai, Wu, Zhicai, Mu, Yingjun
• Primary Examiner(s): Audet, Maury A
• Application Number:
  US16/007,046
• Publication Number:
  US 20180291078A1
• Time in Patent Office: 223 Days
• Field of Search: None
• 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 38/28 Insulins
• CPC Class Codes: A61K 47/55 the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug, i.e. a dimer, oligomer or polymer of pharmacologically or therapeutically active compounds
• 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 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 14/62 Insulins
• CPC Class Codes: C07K 2319/00 Fusion polypeptide

Abstract

Insulin dimers and insulin analog dimers that act as partial agonists at the insulin receptor are disclosed.

Claims

1. A compound selected from the group consisting of

2. A composition comprising one or more compounds of claim 1 and a pharmaceutically acceptable carrier.

3. A method for treating diabetes comprising administering to an individual with diabetes a therapeutically effective amount of a composition comprising the insulin receptor partial agonist of claim 2.

4. The method of claim 3, wherein the diabetes is Type 1 diabetes, Type 2 diabetes, or gestational diabetes.

5. An insulin dimer comprising:

a first B29 or B28 Lys of a first insulin heterodimer molecule having a first A-chain polypeptide and first B-chain polypeptide and a second B29 or B28 Lys of a second insulin heterodimer having a second A-chain polypeptide and second B-chain polypeptide conjugated together by a bifunctional linker selected from the group consisting of;

6. A compound having the following formula