Granted Patent B2

US 12,257,229 · App. 18/068,788 · Granted Mar 25, 2025

Inventor: John J Nestor (Sugar Land, TX)

Assignee: Spitfire Pharma LLC

A61K31/351A61K38/26A61P1/16A61P13/12A61K9/0019A61K45/06A61K47/543A61K47/549

Abstract

Claims (56)

1. A method of treating a fatty liver disease, comprising administering a pharmaceutical composition or a pharmaceutically acceptable salt thereof, to a subject in need thereof, wherein the comprising comprises:

a) SEQ. ID. NO. 1110; and,

b) a pharmaceutically acceptable diluent or buffer;

and wherein the fatty liver disease is non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH) and SEQ ID NO: 1110 is according to Formula III-A aa 1 -aa 2 -aa 3 -aa 4 -aa 5 -aa 6 -aa 7 -aa 8 -aa 9 -aa 10 -aa 11 -aa 12 -aa 13 -aa 14 -aa 15 -aa 16 -aa 17 -aa 18 -aa 19 -aa 20 -aa 21 -aa 22 -aa 23 -aa 24 -aa 25 -aa 26 -aa 27 -aa 28 -aa 29 -Z

wherein:

Z is —OH or —NHR 3 , wherein R 3 is H, unsubstituted or substituted C 1 -C 12 alkyl, or a PEG-containing group of less than 10 kDa;

aa 1 is His;

aa 2 is Aib;

aa 3 is Gln;

aa 4 is Gly;

aa 5 is Thr;

aa 6 is Phe;

aa 7 is Thr;

aa 8 is Ser;

aa 9 is Asp;

aa 10 is Tyr, Glu, Lys or U(X);

aa 11 is Ser;

aa 12 is Lys or Glu;

aa 13 is Tyr;

aa 14 is Leu, Glu or Lys;

aa 15 is Asp;

aa 16 is Glu or Lys;

aa 17 is Gln, Glu or U(X);

aa 18 is Ala;

aa 19 is Ala;

aa 20 is Glu, Lys or U(X);

aa 21 is Glu;

aa 22 is Phe;

aa 23 is Ile;

aa 24 is Gln, Glu or U(X);

aa 25 is Trp;

aa 26 is Leu;

aa 27 is Leu;

aa 28 is Gln;

aa 29 is Thr;

aa 10 and aa 14 , or aa 12 and aa 16 , or aa 16 and aa 20 are cyclized through their side chains to form a lactam linkage; and

provided that one, or at least one of aa 10 , aa 17 , aa 20 and aa 24 is a natural or unnatural amino acid U covalently attached to an alkyl glycoside (X).

2. The method of claim 1 , wherein the treating comprises administering the pharmaceutical composition by subcutaneous, intravenous or intramuscular injection.

3. The method of claim 1 , wherein the treating comprises administering the pharmaceutical composition about once a week.

4. The method of claim 1 , wherein the alkyl glycoside is a 1-alkyl glycoside.

5. The method of claim 1 , wherein the alkyl glycoside comprises a 1-alkyl group comprising an unsubstituted or substituted C 1 -C 30 , C 6 -C 30 , C 6 -C 20 or C 8 -C 20 alkyl.

6. The method of claim 1 , wherein the alkyl glycoside is substituted with one or more groups independently selected from the group consisting of aryl, —OH, —OR 1 , —SH, —SR 1 , —NH 2 , —NHR 1 , —N(R 1 ) 2 , oxo (═O), —C(═O)R 2 , carboxyl (—CO 2 H), carboxylate (—CO 2 − ), —C(═O)OR 1 , —OC(═O)R 3 , —C(═O)N(R 1 ) 2 , —NR 4 C(═O)R 3 , —OC(═O)OR 5 , —OC(═O)N(R 1 ) 2 , —NR 4 C(═O)OR 5 , and —NR 4 C(═O)N(R 1 ) 2 , wherein:

R 1 at each occurrence independently is hydrogen, alkyl or aryl, or both occurrences of R 1 and the nitrogen atom to which they are connected form a heterocyclyl or heteroaryl ring;

R 2 at each occurrence independently is alkyl, heterocyclyl, aryl or heteroaryl;

R 3 at each occurrence independently is hydrogen, alkyl, heterocyclyl, aryl or heteroaryl;

R 4 at each occurrence independently is hydrogen or alkyl; and

R 5 at each occurrence independently is alkyl or aryl.

7. The method of claim 1 , wherein the alkyl glycoside is substituted with a carboxyl or carboxylate group at a distal end of the alkyl group.

8. The method of claim 1 , wherein the treating comprises administration of the pharmaceutical composition by oral inhalation or nasal inhalation or insufflation.

9. The method of claim 1 , wherein the administration of the pharmaceutical composition is in a dose from 0.1 mg to 10 mg, over a period of about one week.

10. The method of claim 1 , wherein the administration of the pharmaceutical composition is in a dose of about 0.1 to 1 mg, over a period of about one week.

11. The method of claim 1 , wherein the fatty liver disease is non-alcoholic fatty liver disease (NAFLD).

12. The method of claim 1 , wherein the fatty liver disease is non-alcoholic steatohepatitis (NASH).

13. The method of claim 1 , further comprising administration of one or more additional therapeutic agents.

14. The method of claim 13 , wherein the one or more additional therapeutic agents are selected from the group consisting of antidiabetic agents, anti-obesity agents, anti-inflammatory agents, antifibrotic agents, antioxidants, anti-hypertensive agents, and combinations thereof.

15. The method of claim 13 , wherein the fatty liver disease is NAFLD or NASH and the one or more additional therapeutic agents are selected from a peroxisome proliferator-activated receptor (PPAR) agonist, a HMG-COA reductase inhibitor, a farnesoid X receptor (FXR) agonist or an antioxidant, or any combination thereof.

Assignments (4)

Continuity (3)

References Cited (400)

Cited By (1)

US 12,551,535