MMP13 binding immunoglobulins

Patent metadata

Field	Value
Publication number	US-12129308-B2
Application number	US-201816617869-A
Country	US
Kind code	B2
Filing date	Jun 4, 2018
Priority date	Jun 2, 2017
Publication date	Oct 29, 2024
Grant date	Oct 29, 2024

Abstract

The present invention relates to immunoglobulins that specifically bind MMP13 and more in particular to polypeptides, nucleic acids encoding such polypeptides; to methods for preparing such polypeptides; to compositions and in particular to pharmaceutical compositions that comprise such polypeptides, for prophylactic, therapeutic or diagnostic purposes. In particular, the immunoglobulins of the present invention inhibit an activity of MMP13 and preferably are also stable.

First claim

The invention claimed is:

1. A polypeptide comprising at least 1 immunoglobulin single variable domain (ISVD) binding matrix metalloproteinase 13 (MMP13); wherein the polypeptide comprises a first ISVD binding MMP13 comprising
3 complementarity determining regions, wherein the complementarity determining regions are CDR1, CDR2, and CDR3, in which
(i) CDR1 is SEQ ID NO: 27;
(ii) CDR2 is SEQ ID NO: 42;

and
(iii) CDR3 is SEQ ID NOs: 56, wherein said polypeptide comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 11 and 111, or comprises a polypeptide which has at least 95% sequence identity to SEQ ID NO: 11.

2. The polypeptide according to claim 1 , wherein said first ISVD binding MMP13 does not inhibit activated human MMP1.

3. The polypeptide according to claim 1 , wherein said polypeptide antagonizes a protease activity of MMP13.

4. The polypeptide according to claim 3 , wherein said polypeptide inhibits bovine collagen I degradation by human MMP13 by at least 20%.

5. The polypeptide according to claim 1 , further comprising a second ISVD.

6. The polypeptide according to claim 5 , wherein the second ISVD specifically binds MMP13.

7. The polypeptide according to claim 6 , wherein the second ISVD specifically binding MMP13 comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7 and 8.

8. The polypeptide according to claim 6 , wherein the polypeptide is SEQ ID NO: 162 or SEQ ID NO: 165.

9. The polypeptide according to claim 1 , further comprising one or two ISVDs that specifically bind Aggrecan.

10. A method of reducing cartilage degeneration in an individual, the method comprising administering the polypeptide according to claim 9 to said individual in an effective amount.

11. The method of claim 10 , wherein said individual has osteoarthritis or rheumatoid arthritis.

12. The polypeptide according to claim 9 , wherein the polypeptide is selected from the group consisting of SEQ ID NO: 176, SEQ ID NO: 177, SEQ ID NO: 178, and SEQ ID NO: 192.

13. The polypeptide according to claim 1 , further comprising an ISVD binding serum albumin.

14. The polypeptide according to claim 1 , further comprising a C-terminal extension, wherein said C-terminal extension is a C-terminal extension (X)n, in which n is 1 to 10; and each X is an amino acid residue that is independently selected the group consisting of alanine (A), glycine (G), valine (V), leucine (L) and isoleucine (I).

15. The polypeptide according to claim 14 , wherein the polypeptide is SEQ ID NO: 192.

16. The polypeptide according to claim 1 , wherein the polypeptide is SEQ ID NO: 194.

Assignees

• Merck Patent Gmbh
• Ablynx Nv

Inventors

• Descamps Francis
• Beste Gerald
• Hermans Guy
• Guehring Hans
• Toleikis Lars
• Ladel Christoph

Classifications

• C07K2317/92

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

• C07K2317/565

  Complementarity determining region [CDR] · CPC title

• A61P19/02

  for joint disorders, e.g. arthritis, arthrosis · CPC title

• A61K39/3955

  against proteinaceous materials, e.g. enzymes, hormones, lymphokines · CPC title

• A61K2039/507

  Comprising a combination of two or more separate antibodies · CPC title