Granted Patent E1

US 50,682 · App. 18/062,103 · Granted Dec 2, 2025

Inventors: Marie-Ange Buyse (Merelbeke, BE); Carlo Boutton (Wielsbeke, BE)

Assignees: Ablynx NV; Sanofi

C07K16/18C07K16/00C07K16/24C07K16/241C07K16/28C07K16/2863C07K16/2866C07K16/2875C07K16/30C07K16/32C07K16/42C07K16/4291

Abstract

Claims (41)

1 . A heavy chain immunoglobulin single variable domain (ISVD) in which the amino acid residue at Kabat position 11 is V and the amino acid residue at Kabat position 89 is L, wherein the heavy chain ISVD specifically binds to:

(A) IL-23 and comprises:

(i) a CDR1 sequence that is the sequence of SEQ ID NO: 173; a CDR2 sequence that is the sequence of SEQ ID NO: 174; and a CDR3 sequence that is the sequence of SEQ ID NO: 175; or

(ii) a CDR1 sequence that is the sequence of SEQ ID NO: 191; a CDR2 sequence that is the sequence of SEQ ID NO: 192; and a CDR3 sequence that is the sequence of SEQ ID NO: 193;

or

(B) TNF and comprises:

a CDR1 sequence that is the sequence of SEQ ID NO: 335; a CDR2 sequence that is the sequence of SEQ ID NO: 336; and a CDR3 sequence that is the sequence of SEQ ID NO: 337.

2 . The heavy chain ISVD of claim 1 , wherein:

the amino acid residue at Kabat position 14 is selected from the group consisting of A and P;

the amino acid residue at Kabat position 41 is selected from the group consisting of A and P;

the amino acid residue at Kabat position 108 is selected from the group consisting of Q and L; and

the amino acid residue at Kabat position 110 is selected from the group consisting of T and Q.

3 . The heavy chain ISVD of claim 1 , further comprising a C-terminal extension (X) n , in which n is 1 to 10, wherein each X is an independently chosen amino acid.

4 . The heavy chain ISVD of claim 3 , wherein each X is an amino acid independently chosen from the group consisting of A, G, V, L, and I.

5 . The heavy chain ISVD of claim 1 , wherein the C-terminal end of the heavy-chain ISVD comprises an amino acid sequence selected from the group consisting of: VTVSS (SEQ ID NO:76), VTVSS(X) n , (SEQ ID NO:77), VKVSS (SEQ ID NO: 95), VKVSS(X) n (SEQ ID NO:97), VQVSS (SEQ ID NO: 96), VQVSS(X) n (SEQ ID NO: 98), in which n is 1 to 10, wherein each X is an independently chosen amino acid.

6 . The heavy chain ISVD of claim 5 , wherein each X is an amino acid independently chosen from the group consisting of A, G, V, L, and I.

7 . The heavy chain ISVD of claim 1 , which is a VHH domain, a humanized VHH domain, or a camelized VH domain.

8 . A fusion polypeptide comprising a heavy chain ISVD according to claim 1 fused to an additional heavy chain ISVD.

9 . The fusion polypeptide of claim 8 , wherein the heavy chain ISVDs are linked directly or via a suitable linker.

10 . The fusion polypeptide of claim 8 , wherein the additional heavy chain ISVD specifically binds to serum albumin.

11 . The fusion polypeptide of claim 10 , wherein the additional heavy chain ISVD has at least 90% sequence identity with Alb-8 (SEQ ID NO:46) or Alb-23 (SEQ ID NO:61).

12 . The fusion polypeptide of claim 10 , wherein the additional heavy chain ISVD comprises a CDR1, CDR2, and CDR3 in which: CDR1 comprises the amino acid sequence SFGMS (SEQ ID NO:41); CDR2 comprises the amino acid sequence SISGSGSDTLYADSVKG (SEQ ID NO:42); and CDR3 comprises the amino acid sequence GGSLSR (SEQ ID NO:43).

13 . A composition comprising a fusion polypeptide according to claim 10 , further comprising at least one pharmaceutically acceptable carrier, diluent or excipient.

14. The heavy chain ISVD of claim 1 , wherein the heavy chain ISVD specifically binds to IL-23 and comprises: a CDR1 sequence that is the sequence of SEQ ID NO: 173; a CDR2 sequence that is the sequence of SEQ ID NO: 174; and a CDR3 sequence that is the sequence of SEQ ID NO: 175.

15. The heavy chain ISVD of claim 14 , wherein:

the amino acid residue at Kabat position 14 is selected from the group consisting of A and P;

the amino acid residue at Kabat position 41 is selected from the group consisting of A and P;

the amino acid residue at Kabat position 108 is selected from the group consisting of Q and L; and

the amino acid residue at Kabat position 110 is selected from the group consisting of T and Q.

16. The heavy chain ISVD of claim 1 , wherein the heavy chain ISVD specifically binds to IL-23 and comprises: a CDR1 sequence that is the sequence of SEQ ID NO: 191; a CDR2 sequence that is the sequence of SEQ ID NO: 192; and a CDR3 sequence that is the sequence of SEQ ID NO: 193.

17. The heavy chain ISVD of claim 16 , wherein:

the amino acid residue at Kabat position 14 is selected from the group consisting of A and P;

the amino acid residue at Kabat position 41 is selected from the group consisting of A and P;

the amino acid residue at Kabat position 108 is selected from the group consisting of Q and L; and

the amino acid residue at Kabat position 110 is selected from the group consisting of T and Q.

18. The heavy chain ISVD of claim 1 , wherein the heavy chain ISVD specifically binds to TNF and comprises: a CDR1 sequence that is the sequence of SEQ ID NO: 335; a CDR2 sequence that is the sequence of SEQ ID NO: 336; and a CDR3 sequence that is the sequence of SEQ ID NO: 337.

19. The heavy chain ISVD of claim 18 , wherein:

the amino acid residue at Kabat position 14 is selected from the group consisting of A and P;

the amino acid residue at Kabat position 41 is selected from the group consisting of A and P;

the amino acid residue at Kabat position 108 is selected from the group consisting of Q and L; and

the amino acid residue at Kabat position 110 is selected from the group consisting of T and Q.

Continuity (8)

References Cited (179)