Granted Patent B2

US 12,337,029 · App. 18/444,485 · Granted Jun 24, 2025

Inventors: Tyler Brown (Cambridge, MA); Kelly Ibsen (Boston, MA)

Assignee: I2O THERAPEUTICS, INC.

A61K38/26A61K9/08A61K31/14A61K38/22A61K47/12A61K47/18A61K47/183A61K47/186A61K47/542A61K47/6845C07K14/575C07K14/605C07K16/241A61K38/00C07K2317/24

Abstract

Claims (60)

1. A compound having the structure of Formula I:

wherein:

R 1 , R 2 , and R 3 are independently C 1 -C 5 alkyl, wherein at least one of R 1 , R 2 , and R 3 is C 2 -C 5 alkyl;

R 4 is C 2 -C 5 alkyl, wherein the C 2 -C 5 alkyl is unsubstituted or substituted with 1 or more hydroxyl; and

 is a therapeutic agent having the following configuration:

[diacid]-[linker]-[an amylin analog];

wherein the amylin analog has the amino acid sequence of

(SEQ ID NO: 20)

KCNTATCATQRLANFLVHSSNNFGPILPPTNVGSNTY-amide,

 with a proviso that the amino acid sequence comprises one or more of the following amino acid substitutions: N14E, V17R, Y37P, F15E, L16E, V17E, or any combination thereof; and

wherein the compound has a

molar ratio of from about 1:1 to about 1:3.

2. The compound of claim 1 , wherein Cys at position 2 and Cys at position 7 of the amino acid sequence of the amylin analog forms a disulfide bond.

3. The compound of claim 2 , wherein the sequence of SEQ ID NO: 20 with the configuration of [diacid]-[linker]-[an amylin analog] has the following structure:

4. The compound of claim 3 , wherein the amino acid sequence has the amino acid substitutions of N14E, V17R, and Y37P.

5. The compound of claim 2 , wherein:

(i) R 1 , R 2 , and R 3 are ethyl;

(ii) R 1 , R 2 , and R 3 are propyl;

(iii) R 1 and R 2 are methyl, and R 3 is ethyl;

(iv) R 1 and R 2 are ethyl, and R 3 is methyl; or

(v) R 1 and R 2 are propyl, and R 3 is methyl.

6. The compound of claim 2 , wherein R 4 is C 2 -C 5 alkyl substituted with a hydroxyl, or R 4 is

7. The compound of claim 2 , wherein the compound has the structure of Formula Ib or Formula Ic:

8. The compound of claim 3 , wherein the compound consists of)

molar ratio of about 1:1.

9. The compound of claim 2 , wherein the linker of the therapeutic agent comprises one or more gamma glutamate (γGlu) residues, one or more 8-amino-3,6-dioxaoctanoic acid (OEG) residues, or a combination thereof.

10. The compound of claim 2 , wherein the diacid of the therapeutic agent comprises a C 10 , C 12 , C 14 , C 16 , C 18 , or C 20 fatty diacid.

11. The compound of claim 3 , wherein the compound consists of

having a molar

ratio of about 1:2.

12. The compound of claim 3 , wherein the compound consists of

having a

molar ratio of about 1:3.

13. The compound of claim 4 , wherein the compound consists of

having a

molar ratio of about 1:1.

14. The compound of claim 4 , wherein the compound consists of

having a

molar ratio of about 1:2.

15. A method of treating a disease or disorder in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the compound of claim 2 ,

wherein the administering is effective to treat the disease or disorder in the subject, and

wherein the disease or disorder is a metabolic disease or disorder.

16. The method of claim 15 , wherein the metabolic disease or disorder is selected from the group consisting of type 1 diabetes, type 2 diabetes, obesity, overweight, and nonalcoholic steatohepatitis (NASH).

17. The method of claim 15 , wherein the metabolic disease or disorder is type 2 diabetes.

18. The method of claim 15 , wherein the metabolic disease or disorder is obesity.

19. The method of claim 15 , wherein the compound is administered via subcutaneous administration, intravenous administration, or oral administration.

20. A method of reducing weight in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the compound of claim 2 ,

wherein the administering is effective to reduce weight in the subject.

21. A method of treating a disease or disorder in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the compound of claim 4 ,

wherein the administering is effective to treat the disease or disorder in the subject, and

wherein the disease or disorder is a metabolic disease or disorder.

22. The method of claim 21 , wherein the metabolic disease or disorder is selected from the group consisting of type 1 diabetes, type 2 diabetes, obesity, overweight, and nonalcoholic steatohepatitis (NASH).

23. The method of claim 21 , wherein the metabolic disease or disorder is type 2 diabetes.

24. The method of claim 21 , wherein the metabolic disease or disorder is obesity.

25. The method of claim 21 , wherein the compound is administered via subcutaneous administration, intravenous administration, or oral administration.

26. A method of reducing weight in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the compound of claim 4 ,

wherein the administering is effective to reduce weight in the subject.

27. The compound of claim 4 , wherein the compound consists of

having a

molar ratio of about 1:3.

Assignments (1)

Continuity (6)

References Cited (370)