GROWTH DIFFERENTIATION FACTOR 15 AGONIST COMPOUNDS AND METHODS OF USING THE SAME

• US 20190309033A1
• Filed: 03/29/2019
• Published: 10/10/2019
• Est. Priority Date: 04/06/2018
• Status: Active Grant

• Current Assignee: Eli Lilly and Company
• Original Assignee: Eli Lilly and Company
• Inventors: Gonciarz, Malgorzata Donata, Obungu, Victor H., Pickard, Richard Todd
• Granted Patent: US 11,104,711 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 47/65 Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers
• 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: C07K 14/475 Growth factors; Growth regulators
• CPC Class Codes: C07K 14/495 Transforming growth factor [TGF]
• CPC Class Codes: C07K 16/1036 Retroviridae, e.g. leukemia viruses
• CPC Class Codes: C07K 16/18 against material from animals or humans

Abstract

Compounds are provided herein for inducing weight loss and for treating diabetes, dyslipidemia, NASH and/or obesity. Also provided are pharmaceutical compositions containing such compounds and therapeutic uses of such compounds and compositions, where such compounds act as GDF15 agonists with extended time of action and other advantageous properties.

Claims

1. A compound comprising SEQ ID NO:

2.

3. A homodimer comprising two compounds of claim 1, wherein the compounds are linked via at least one interchain disulfide bond between a cysteine residue of the first compound and a cysteine residue of the second compound.

4. A pharmaceutical composition comprising the compound of claim 1 and one or more pharmaceutically acceptable excipients.

5. A method of inducing weight loss in an individual, the method comprising the step of:

administering to the individual an effective amount of the compound of claim 1 or the composition of claim 4.

6. A method of treating type 2 diabetes in an individual, the method comprising the step of:

administering to the individual an effective amount of the compound of claim 1 or the composition of claim 4.

7. A method of treating obesity in an individual, the method comprising the step of:

administering to the individual an effective amount of the compound of claim 1 or the composition of claim 4.

8. A method of treating nonalcoholic steatohepatitis (NASH) in an individual, the methods comprising the step of:

administering to the individual an effective amount of the compound of claim 1 or the composition of claim 4.

9. A method of treating dyslipidemia in an individual, the method comprising the step of:

administering to the individual an effective amount of the compound of claim 1 or the composition of claim 4.

2. A compound consisting of SEQ ID NO:

2.

10. A compound produced by cultivating a mammalian cell comprising a cDNA molecule encoding a polypeptide comprising an amino acid sequence of SEQ ID NO:

2 under such conditions that the polypeptide is expressed, and recovering the compound.