US 11,813,307 B2
Polypeptides binding ADAMTS5, MMP13 and aggrecan
Soren Steffensen, Etterbeek (BE); Gerald Beste, Ghent (BE); Hans Guehring, Geissenheim (DE); Lars Toleikis, Kleinniedesheim (DE); Christoph Ladel, Darmstadt (DE); Sven Lindemann, Darmstadt (DE); Roland Kellner, Heppenheim (DE); and Ralf Guenther, Griesheim (DE)
Assigned to MERCK PATENT GMBH, Darmstadt (DE); and ABLYNX NV, Zwijnaarde (BE)
Appl. No. 16/617,846
Filed by Merck Patent GmbH, Darmstadt (DE); and ABLYNX NV, Zwijnaarde (BE)
PCT Filed Jun. 4, 2018, PCT No. PCT/EP2018/064668
§ 371(c)(1), (2) Date Nov. 27, 2019,
PCT Pub. No. WO2018/220236, PCT Pub. Date Dec. 6, 2018.
Claims priority of application No. 17174404 (EP), filed on Jun. 2, 2017.
Prior Publication US 2021/0008160 A1, Jan. 14, 2021
Int. Cl. C07K 16/40 (2006.01); A61K 38/17 (2006.01); C07K 1/14 (2006.01)
CPC A61K 38/177 (2013.01) [C07K 1/14 (2013.01); C07K 2317/31 (2013.01); C07K 2317/565 (2013.01); C07K 2317/569 (2013.01)] 13 Claims
 
1. A polypeptide comprising at least 3 ISVDs, in which a first ISVD specifically binds matrix metalloproteinase 13 (MMP13), a second ISVD specifically binds ADAMTS5 and a third ISVD specifically binds Aggrecan;
wherein said ISVD specifically binding MMP13 comprises 3 complementarity determining regions, wherein the complementarity determining regions are CDR1 to CDR3, in which
(i) CDR1 comprises SEQ ID NO: 8;
(ii) CDR2 comprises SEQ ID NO: 10; and
(iii) CDR3 comprises SEQ ID NO: 12;
wherein said ISVD specifically binding ADAMTS5 comprises 3 complementarity determining regions, wherein the complementarity determining regions are CDR1 to CDR3, in which
(i) CDR1 comprises SEQ ID NO: 14;
(ii) CDR2 comprises SEQ ID NO: 16; and
(iii) CDR3 comprises SEQ ID NO: 18; and
wherein said ISVD specifically binding Aggrecan comprises 3 complementarity determining regions, wherein the complementarity determining regions are CDR1 to CDR3, in which
(i) CDR1 comprises (a) SEQ ID NO: 19, or (b) an amino acid sequence according to SEQ ID NO: 19 that has amino acid substitutions at positions 7 and/or 9, wherein the amino acid substitutions are:
N at position 7 in SEQ ID NO: 19 changed to S; and/or
V at position 9 changed to M;
(ii) CDR2 comprises (a) SEQ ID NO: 21, or (b) an amino acid sequence according to SEQ ID NO: 21 that has amino acid substitutions at positions 1, 3, 4, 8, 9, and/or combinations thereof, wherein the amino acid substitutions are:
T at position 1 in SEQ ID NO: 21 changed to A;
S at position 3 in SEQ ID NO: 21 changed to R;
S at position 4 in SEQ ID NO: 21 changed to T;
A at position 8 in SEQ ID NO: 21 changed to T; and/or
N at position 9 in SEQ ID NO: 21 changed to D; and
(iii) CDR3 comprises (a) SEQ ID NO: 23, or (b) an amino acid sequence according to SEQ ID NO: 23 that has amino acid substitutions at positions 4 and/or 8, wherein the amino acid substitutions are:
H at position 4 in SEQ ID NO: 23 changed to R; and/or
V at position 8 in SEQ ID NO: 23 changed to D.