IP Library › Granted Patent US 12,195,510
Granted Patent B2
US 12,195,510 · App. 17/329,558 · Granted Jan 14, 2025

Insulin conjugates

Inventors: Stefan Guessregen (Frankfurt am Main, DE); Martin Will (Frankfurt am Main, DE); Thomas Boehme (Frankfurt am Main, DE); Marcus Hermann Korn (Frankfurt am Main, DE)
C07K14/62A61K31/18A61K47/64
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Quick Facts
Patent No.
US 12,195,510
App. No.
17/329,558
Granted
Jan 14, 2025
Kind
B2
Abstract

The present invention relates to a conjugate comprising a sulfonamide of formula (I) and an active pharmaceutical ingredient such as an insulin analog comprising at least one mutation relative to the parent insulin, wherein the insulin analog comprises a mutation at position B16 which is substituted with a hydrophobic amino acid and/or a mutation at position B25 which is substituted with a hydrophobic amino acid. The present invention further relates to a sulfonamide of formula (A). Moreover, the present invention relates to an insulin analog comprising at least one mutation relative to the parent insulin.

Claims (105)

1. An insulin comprising a chain A and a chain B, wherein the insulin comprises:

(a) a mutation in chain A at position A14, or at positions A14 and A21, wherein position A14 is substituted with Glutamic Acid (Glu), Aspartic acid (Asp), or Histidine (His); and

(b) at least one a mutation in the chain B at position B25, or at position B25 in combination with positions B3, B16 and/or B30 wherein position B16 and/or B25 is substituted with a branched-chain amino acid,

wherein the insulin has two to six mutations relative to human insulin.

2. The insulin of claim 1 , wherein the branched-chain amino acid of each mutation is independently selected from the group consisting of valine (Val), isoleucine (Ile), and leucine (Leu).

3. The insulin of claim 1 , wherein the mutation at position A14 of the A chain is a substitution of A14 with glutamic acid (Glu).

4. The insulin of claim 1 , wherein the mutation at position B30 of the B chain is a deletion of the amino acid at position B30 (Des (B30)-mutation).

5. The insulin of claim 1 , wherein the mutation at position B3 of the B chain is a substitution at position B3 with glutamic acid (Glu).

6. The insulin of claim 1 , wherein the mutation at position A21 of the A chain is a substitution at position A21 with glycine (Gly).

7. The insulin of claim 1 , wherein the B chain comprises an amino acid sequence selected from the group consisting of:

(SEQ ID NO: 22)

FVNQHLCGSHLVEALYLVCGERGELYTPK,

(SEQ ID NO: 44)

FVNQHLCGSHLVEALYLVCGERGFIYTPK,

(SEQ ID NO: 48)

FVNQHLCGSHLVEALYLVCGERGFVYTPK,

(SEQ ID NO: 50)

FVEQHLCGSHLVEALYLVCGERGFVYTPK,

(SEQ ID NO: 58)

FVNQHLCGSHLVEALILVCGERGFIYTPK,

(SEQ ID NO: 60)

FVEQHLCGSHLVEALILVCGERGFIYTPK,

(SEQ ID NO: 64)

FVNQHLCGSHLVEALILVCGERGFVYTPK,

(SEQ ID NO: 66)

FVEQHLCGSHLVEALILVCGERGFVYTPK,

(SEQ ID NO: 70)

FVNQHLCGSHLVEALVLVCGERGFIYTPK,

(SEQ ID NO: 76)

FVNQHLCGSHLVEALVLVCGERGFVYTPK,

(SEQ ID NO: 78)

FVEQHLCGSHLVEALVLVCGERGFVYTPK,

(SEQ ID NO: 80)

FVEQHLCGSHLVEALVLVCGERGFVYTPK,

(SEQ ID NO: 85)

FVNQHLCGSHLVEALYLVCGERGELYTPKT,

(SEQ ID NO: 86)

FVNQHLCGSHLVEALYLVCGERGFVYTPKT,

(SEQ ID NO: 87)

FVNQHLCGSHLVEALYLVCGERGFIYTPKT,

(SEQ ID NO: 88)

FVNQHLCGSHLVEALYLVCGERGFVYTPKT,

(SEQ ID NO: 89)

FVEQHLCGSHLVEALYLVCGERGFVYTPKT,

(SEQ ID NO: 90)

FVNQHLCGSHLVEALILVCGERGFIYTPKT,

(SEQ ID NO: 91)

FVEQHLCGSHLVEALILVCGERGFIYTPKT,

(SEQ ID NO: 92)

FVNQHLCGSHLVEALILVCGERGFVYTPKT,

(SEQ ID NO: 93)

FVEQHLCGSHLVEALILVCGERGFVYTPKT,

(SEQ ID NO: 94)

FVNQHLCGSHLVEALVLVCGERGFIYTPKT,

(SEQ ID NO: 95)

FVNQHLCGSHLVEALVLVCGERGFVYTPKT,

(SEQ ID NO: 96)

FVEQHLCGSHLVEALVLVCGERGFVYTPKT,

and

(SEQ ID NO: 97)

FVEQHLCGSHLVEALVLVCGERGFVYTPKT.

8. The insulin of claim 1 , wherein the A chain has an amino acid sequence as shown in SEQ ID NO: 43 and the B chain has an amino acid sequence as shown in SEQ ID NO: 44.

9. The insulin of claim 1 , wherein the A chain has an amino acid sequence as shown in SEQ ID NO: 47 and the B chain has an amino acid sequence as shown in SEQ ID NO: 48.

10. The insulin of claim 1 , wherein the A chain has an amino acid sequence as shown in SEQ ID NO: 77 and the B chain has an amino acid sequence as shown in SEQ ID NO: 78.

11. The insulin of claim 1 , wherein the mutation at position A21 of the A chain is a substitution at position A21 with Aspartic acid (Asp).

12. The insulin of claim 1 , wherein the mutation at position A21 of the A chain is a substitution at position A21 with Histidine (His).

13. The insulin of claim 1 , wherein the branched-chain amino acid of each mutation is valine (Val).

14. The insulin of claim 1 , wherein the branched-chain amino acid of each mutation is isoleucine (Ile).

15. The insulin of claim 1 , wherein the branched-chain amino acid of each mutation is leucine (Leu).

16. An insulin selected from the group consisting of:

Glu(A14)Leu(B16)Des(B30)-human insulin,

Glu(A14)Ile(B16)Des(B30)-human insulin,

Glu(A14)Val(B16)Des(B30)-human insulin,

Glu(A14)Leu(B16)-human insulin,

Glu(A14)Ile(B16)-human insulin,

Glu(A14)Val(B16)-human insulin,

Glu(A14)Leu(B25)Des(B30)-human insulin,

Glu(A14)Ile(B25)Des(B30)-human insulin,

Glu(A14)Val(B25)Des(B30)-human insulin,

Glu(A14)Leu(B25)-human insulin,

Glu(A14)Ile(B25)-human insulin,

Glu(A14)Val(B25)-human insulin,

Glu(A14)Gly(A21)Glu(B3)Val(B25)Des(B30)-human insulin,

Glu(A14)Ile(B16)Ile(B25)Des(B30)-human insulin,

Glu(A14)Glu(B3)Ile(B16)Ile(B25)Des(B30)-human insulin,

Glu(A14)Ile(B16)Val(B25)Des(B30)-human insulin,

Glu(A14)Gly(A21)Glu(B3)Ile(B16)Val(B25)Des(B30)-human insulin,

Glu(A14)Val(B16)Ile(B25)Des(B30)-human insulin,

Glu(A14)Val(B16)Val(B25)Des(B30)-human insulin,

Glu(A14)Glu(B3)Val(B16)Val(B25)Des(B30)-human insulin,

Glu(A14)Gly(A21)Glu(B3)Val(B16)Val(B25)Des(B30)-human insulin,

Glu(A14)Gly(A21)Glu (B3)Val(B25)-human insulin,

Glu(A14)Ile(B16)Ile(B25)-human insulin,

Glu(A14)Glu(B3)Ile(B16)Ile(B25)-human insulin,

Glu(A14)Ile(B16)Val(B25)-human insulin,

Glu(A14)Gly(A21)Glu(B3)Ile(B16)Val(B25)-human insulin,

Glu(A14)Val(B16)Ile(B25)-human insulin,

Glu(A14)Val(B16)Val(B25)-human insulin,

Glu(A14)Glu(B3)Val(B16)Val(B25)-human insulin, and

Glu(A14)Gly(A21)Glu(B3)Val(B16)Val(B25)-human insulin.

17. An insulin comprising Glu(A14)Val(B25)Des(B30)-human insulin.

18. An insulin comprising Glu(A14)Ile(B25)Des(B30)-human insulin.

19. An insulin comprising Glu(A14)Val(B16) Val(B25)Des(B30)-human insulin.

20. The insulin of claim 1 , wherein the insulin comprises two to five mutations in amino acid sequence.

21. The insulin of claim 1 , wherein the insulin comprises two to four mutations in amino acid sequence.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 25, 2024
From: GUESSREGEN, STEFAN; WILL, MARTIN; BOEHME, THOMAS; KORN, MARCUS HERMANN
To: SANOFI
Reel/Frame 069398/0964 →
Priority Claims (3)
EP 18306657 · Dec 11, 2018 · regional
EP 18306658 · Dec 11, 2018 · regional
EP 18306659 · Dec 11, 2018 · regional
Continuity (2)
Division 16709208 · Dec 10, 2019
Related Publication 20220048968A1 · Feb 17, 2022
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