Polypeptides comprising immunoglobulin single variable domains targeting TNFα and IL-23

Patent metadata

Field	Value
Publication number	US-12528860-B2
Application number	US-202217727876-A
Country	US
Kind code	B2
Filing date	Apr 25, 2022
Priority date	Dec 6, 2019
Publication date	Jan 20, 2026
Grant date	Jan 20, 2026

Abstract

The present technology aims at providing a novel type of drug. Specifically, the present technology provides polypeptides comprising at least three immunoglobulin single variable domains (ISVDs), characterized in that at least one ISVD binds to TNFα and at least two ISVDs bind to IL-23. The present technology also provides nucleic acids, vectors and compositions.

First claim

The invention claimed is:

1 . A nucleic acid comprising a nucleotide sequence that encodes a polypeptide that specifically binds TNFα and the p19 subunit of IL-23, wherein the polypeptide comprises at least three immunoglobulin single variable domains (ISVDs), wherein each of said ISVDs comprises three complementarity determining regions (CDR1 to CDR3, respectively), optionally linked via one or more peptidic linkers; and wherein:
a) a first ISVD comprises
i. a CDR1 that is the amino acid sequence of SEQ ID NO: 6;
ii. a CDR2 that is the amino acid sequence of SEQ ID NO: 10; and
iii. a CDR3 that is the amino acid sequence of SEQ ID NO: 14;

b) a second ISVD comprises
iv. a CDR1 that is the amino acid sequence of SEQ ID NO: 7;
v. a CDR2 that is the amino acid sequence of SEQ ID NO: 11; and
vi. a CDR3 that is the amino acid sequence of SEQ ID NO: 15; and

c) a third ISVD comprises
vii. a CDR1 that is the amino acid sequence of SEQ ID NO: 9;
viii. a CDR2 that is the amino acid sequence of SEQ ID NO: 13; and
ix. a CDR3 that is the amino acid sequence of SEQ ID NO: 17.

2 . The nucleic acid according to claim 1 , wherein:
a) said first ISVD consists of the amino acid sequence of SEQ ID NO: 2; b) said second ISVD consists of the amino acid sequence of SEQ ID NO: 3; and c) said third ISVD consists of the amino acid sequence of SEQ ID NO: 5.

3 . The nucleic acid according to claim 1 , wherein said polypeptide further comprises an ISVD binding to human serum albumin which comprises:
i. a CDR1 that is the amino acid sequence of SEQ ID NO: 8; ii. a CDR2 that is the amino acid sequence of SEQ ID NO: 12; and iii. a CDR3 that is the amino acid sequence of SEQ ID NO: 16.

4 . The nucleic acid according to claim 1 , wherein the polypeptide consists of four immunoglobulin single variable domains (ISVDs), wherein each of said ISVDs comprises three complementarity determining regions (CDR1 to CDR3, respectively), optionally linked via one or more peptidic linkers; and wherein:
a) a first ISVD comprises
i. a CDR1 that is the amino acid sequence of SEQ ID NO: 6;
ii. a CDR2 that is the amino acid sequence of SEQ ID NO: 10; and
iii. a CDR3 that is the amino acid sequence of SEQ ID NO: 14;
b) a second ISVD comprises
iv. a CDR1 that is the amino acid sequence of SEQ ID NO: 7;
v. a CDR2 that is the amino acid sequence of SEQ ID NO: 11; and
vi. a CDR3 that is the amino acid sequence of SEQ ID NO: 15;
c) a third ISVD comprises
vii. a CDR1 that is the amino acid sequence of SEQ ID NO: 9;
viii. a CDR2 that is the amino acid sequence of SEQ ID NO: 13; and
ix. a CDR3 that is the amino acid sequence of SEQ ID NO: 17; and
d) a fourth ISVD comprises
x. a CDR1 that is the amino acid sequence of SEQ ID NO: 8;
xi. a CDR2 that is the amino acid sequence of SEQ ID NO: 12; and
xii. a CDR3 that is the amino acid sequence of SEQ ID NO: 16.

5 . The nucleic acid according to claim 4 , wherein:
a) said first ISVD consists of the amino acid sequence of SEQ ID NO: 2; b) said second ISVD consists of the amino acid sequence of SEQ ID NO: 3; c) said third ISVD consists of the amino acid sequence of SEQ ID NO: 5; and d) said fourth ISVD consists of the amino acid sequence of SEQ ID NO: 4.

6 . A nucleic acid comprising a nucleotide sequence that encodes a polypeptide comprising the amino acid sequence of SEQ ID NO: 1.

7 . A nucleic acid comprising a nucleotide sequence that encodes a polypeptide consisting of the amino acid sequence of SEQ ID NO: 1.

8 . A host cell comprising the nucleic acid according to claim 1 .

9 . A host cell comprising the nucleic acid according to claim 2 .

10 . A host cell comprising the nucleic acid according to claim 3 .

11 . A host cell comprising the nucleic acid according to claim 4 .

12 . A host cell comprising the nucleic acid according to claim 5 .

13 . A host cell comprising the nucleic acid according to claim 6 .

14 . A host cell comprising the nucleic acid according to claim 7 .

15 . A method for producing a polypeptide, said method comprising the steps of:
a) expressing, in a suitable host cell, the nucleic acid according to claim 1 ; and b) optionally isolating and/or purifying the polypeptide.

Assignees

• Ablynx Nv
• Sanofi Sa
• Ablynx Nv

Inventors

• Rommelaere Heidi
• Asbrand Christian
• Brigé Ann
• Cornelis Sigrid
• Lorent Eric

Classifications

• A61K39/395

  Antibodies (agglutinins A61K38/36 {; as drug carriers A61K47/50}); Immunoglobulins; Immune serum, e.g. antilymphocytic serum · CPC title

• C07K2317/92

  Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value · CPC title

• C07K2317/76

  Antagonist effect on antigen, e.g. neutralization or inhibition of binding · CPC title

• C07K2317/569

  Single domain, e.g. dAb, sdAb, VHH, VNAR or nanobody® · CPC title

• C07K2317/565

  Complementarity determining region [CDR] · CPC title