IP Library Granted Patent US 10,004,782
Granted Patent B2
US 10,004,782 · App. 14/071,976 · Granted Jun 26, 2018

Glucokinase activator compositions for the treatment of diabetes

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Quick Facts
Patent No.
US 10,004,782
App. No.
14/071,976
Granted
Jun 26, 2018
Kind
B2
Abstract

The present invention relates to pharmaceutical compositions comprising {2-[3-cyclohexyl-3-(trans-4-propoxy-cyclohexyl)-ureido]-thiazol-5-ylsulfanyl}-acetic acid (FRI-1) in combination with an anti-diabetic drug selected from the group consisting of metformin, sitagliptin or exenatide. The present invention also relates to the use of the pharmaceutical compositions in restoring insulin sensitivity and treating type II diabetes, including reducing body weight in subjects undergoing type II diabetes treatment.

Claims (19)

1. A pharmaceutical composition comprising: i) {2-[3-cyclohexyl-3-(trans-4-propoxy-cyclohexyl)-ureido]-thiazol-5-ylsulfanyl}-acetic acid or a pharmaceutically acceptable salt thereof, ii) a GLP-1 analog or a pharmaceutically acceptable salt thereof; and iii) at least one pharmaceutically acceptable carrier, excipient, diluent or mixture thereof.

2. The composition of claim 1 , wherein the GLP-1 analog is exenatide, or a pharmaceutically acceptable salt thereof.

3. A method of treating type II diabetes comprising administering to a subject a glucokinase activator that is {2-[3-cyclohexyl-3-(trans-4-propoxy-cyclohexyl)-ureido]-thiazol-5-ylsulfanyl}-acetic acid or a pharmaceutically acceptable salt thereof and administering to the subject a GLP-1 analog or a pharmaceutically acceptable salt thereof, wherein insulin sensitivity in the subject is increased.

4. The method of claim 3 , wherein the subject is a human.

5. The method of claim 3 , wherein the glucokinase activator and the GLP-1 analog are administered in discrete dosage forms.

6. The method of claim 3 , wherein the glucokinase activator and the GLP-1 analog are administered in a single dosage form.

7. The method of claim 3 , wherein the GLP-1 analog is administered by injection and the glucokinase activator is administered orally.

8. The method of claim 3 , wherein the GLP-1 analog is exenatide or a pharmaceutically acceptable salt thereof.

9. A method of improving glycemic control by increasing a subject's insulin sensitivity comprising administering to a subject a glucokinase activator that is {2-[3-cyclohexyl-3-(trans-4-propoxy-cyclohexyl)-ureido]-thiazol-5-ylsulfanyl}-acetic acid or a pharmaceutically acceptable salt thereof and administering to the subject a GLP-1 analog or a pharmaceutically acceptable salt thereof.

10. The method of claim 9 , wherein the subject is a human.

11. The method of claim 9 , wherein the glucokinase activator and the GLP-1 analog are administered in discrete dosage forms.

12. The method of claim 9 , wherein the glucokinase activator and the GLP-1 analog are administered in a single dosage form.

13. The method of claim 9 , wherein the GLP-1 analog is administered by injection and the glucokinase activator is administered orally.

14. The method of claim 9 , wherein the GLP-1 analog is exenatide or a pharmaceutically acceptable salt thereof.

15. A method of treating a condition in a subject by increasing the subject's insulin sensitivity comprising administering to a subject {2-[3-cyclohexyl-3-(trans-4-propoxy-cyclohexyl)-ureido]-thiazol-5-ylsulfanyl}-acetic acid or a pharmaceutically acceptable salt thereof and administering a GLP-1 analog or a pharmaceutically acceptable salt thereof, wherein the condition is selected from the group consisting of a metabolic disorder, glucose intolerance, prediabetic state, insulin resistance, hyperglycemia, impaired glucose tolerance (IGT), Syndrome X, impaired fasting glucose (IFG), dyslipidemia, hyperlipidemia, hyperlipoproteinemia, hypertension, osteoporosis, non-alcoholic fatty liver disease (NAFLD), complications resulting from or associated with diabetes, cardiovascular disease, and obesity.

16. The method of claim 15 , wherein i) the complication resulting from or associated with diabetes is selected from the group consisting of nephropathy, retinopathy, neuropathy and impaired wound healing or ii) the cardiovascular disease is selected from the group consisting of arteriosclerosis and atherosclerosis.

17. A method of improving insulin sensitivity in a subject comprising administering to the subject {2-[3-cyclohexyl-3-(trans-4-propoxy-cyclohexyl)-ureido]-thiazol-5-ylsulfanyl}-acetic acid or a pharmaceutically acceptable salt thereof and administering to the subject a GLP-1 analog or a pharmaceutically acceptable salt thereof.

18. The method of claim 15 , wherein the subject is a human.

19. The method of claim 17 , wherein the subject is a human.

Assignments (12)
RELEASE OF SECURITY INTEREST Recorded Jan 27, 2021
From: HORIZON TECHNOLOGY FINANCE CORPORATION, AS COLLATERAL AGENT
To: VTV THERAPEUTICS LLC
Reel/Frame 055133/0214 →
SECURITY INTEREST Recorded Apr 18, 2018
From: VTV THERAPEUTICS LLC
To: HORIZON TECHNOLOGY FINANCE CORPORATION, AS COLLATERAL AGENT
Reel/Frame 045969/0774 →
CORRECTIVE ASSIGNMENT TO CORRECT THE RECEIVING PARTY DATA PREVIOUSLY RECORDED AT REEL: 036254 FRAME: 0780. ASSIGNOR(S) HEREBY CONFIRMS THE ASSIGNMENT. Recorded Sep 24, 2015
From: M&F TTP HOLDINGS LLC, AS COLLATERAL AGENT
To: VTVX HOLDINGS I LLC
Reel/Frame 036675/0407 →
RELEASE OF SECURITY INTEREST Recorded Aug 3, 2015
From: M&F TTP HOLDINGS LLC, AS COLLATERAL AGENT
To: VTVX HOLDINGS II LLC
Reel/Frame 036254/0780 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 31, 2015
From: VTVX HOLDINGS I LLC
To: VTV THERAPEUTICS LLC
Reel/Frame 036242/0354 →
CHANGE OF NAME Recorded Jul 30, 2015
From: VTV THERAPEUTICS LLC
To: VTVX HOLDINGS I LLC
Reel/Frame 036236/0165 →
CHANGE OF NAME Recorded Jun 25, 2015
From: TRANSTECH PHARMA, LLC
To: VTV THERAPEUTICS LLC
Reel/Frame 036026/0219 →
SECURITY INTEREST Recorded Feb 26, 2015
From: TRANSTECH PHARMA, LLC
To: M&F TTP HOLDINGS LLC, AS COLLATERAL AGENT
Reel/Frame 035103/0356 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 27, 2013
From: VALCARCE LOPEZ, MARIA CARMEN
To: TRANSTECH PHARMA, LLC
Reel/Frame 031686/0408 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 27, 2013
From: FONG, TUNG
To: FOREST LABORATORIES HOLDINGS LIMITED
Reel/Frame 031686/0390 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 27, 2013
From: FOREST LABORATORIES HOLDINGS LIMITED
To: TRANSTECH PHARMA, LLC
Reel/Frame 031686/0393 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 26, 2013
From: TRANSTECH PHARMA, INC.
To: TRANSTECH PHARMA, LLC
Reel/Frame 031678/0682 →
Cited By (4)
US 12,318,366 US 12,391,658 US 12,479,808 US 12,709,603