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

Patent metadata

Field	Value
Publication number	US-11332525-B2
Application number	US-202117502332-A
Country	US
Kind code	B2
Filing date	Oct 15, 2021
Priority date	Dec 6, 2019
Publication date	May 17, 2022
Grant date	May 17, 2022

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 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 polypeptide 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 polypeptide 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 polypeptide 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 polypeptide 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 polypeptide comprising the amino acid sequence of SEQ ID NO: 1.

7. A polypeptide consisting of the amino acid sequence of SEQ ID NO: 1.

8. A composition comprising the polypeptide according to claim 1 .

9. A composition comprising the polypeptide according to claim 2 .

10. A composition comprising the polypeptide according to claim 3 .

11. A composition comprising the polypeptide according to claim 4 .

12. A composition comprising the polypeptide according to claim 5 .

13. A composition comprising the polypeptide according to claim 6 .

14. A composition comprising the polypeptide according to claim 7 .

Assignees

• Ablynx Nv
• Sanofi Sa

Inventors

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

Classifications

• 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

• C07K16/244 Primary

  Interleukins [IL] · CPC title

• C07K16/241 Primary

  Tumor Necrosis Factors · CPC title

• C07K16/18

  against material from animals or humans · CPC title