Aggrecan binding immunoglobulins
AssigneesAblynx N.V., Merck Patent GmbH
InventorsSoren Steffensen, Gerald Beste, Guy Hermans, Hans Gühring, Christoph Ladel, Lars Toleikis
Life of this patent
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Abstract
The present invention relates to immunoglobulins that specifically bind Aggrecan 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 the activity of Aggrecan.
Claims18
A polypeptide comprising an immunoglobulin single variable domain (ISV) that specifically binds to Aggrecan, wherein the ISV that specifically binds Aggrecan essentially consists of 4 framework regions (FR1 to FR4, respectively) and 3 complementarity determining regions (CDR1 to CDR3, respectively), in which:
- i) CDR1 is chosen from the group consisting of:
- a) SEQ ID NO:
- 32;
- and
- b) amino acid sequences that have 3, 2, or 1 amino acid(s) difference with the amino acid sequence of SEQ ID NO:
- 32, wherein
- at position 2 the R has been changed into L;
- at position 6 the S has been changed into T;
- and/or
- at position 8 the T has been changed into A;
- and
- ii) CDR2 is chosen from the group consisting of:
- c) SEQ ID NO:
- 50;
- and
- d) amino acid sequences that have 2 or 1 amino acid(s) difference with the amino acid sequence of SEQ ID NO:
- 50, wherein
- at position 7 the G has been changed into S or R;
- and/or
- at position 8 the R has been changed into T;
- and
- iii) CDR3 is chosen from the group consisting of:
- e) SEQ ID NO:
- 68;
- and
- f) amino acid sequences that have 5, 4, 3, 2, or 1 amino acid(s) difference with the amino acid sequence of SEQ ID NO:
- 68, wherein
- at position 4 the R has been changed into V, or P;
- at position 6 the A has been changed into Y;
- at position 7 the S has been changed into T;
- at position 8 the S is absent;
- at position 9 the N has been changed into P;
- at position 10 the R has been changed into T or L;
- at position 11 the G has been changed into E;
- and/or
- at position 12 the L has been changed into T or V;
- wherein:
- CDR1 is SEQ ID NO:
- 32, CDR2 is SEQ ID NO:
- 50, and CDR3 is SEQ ID NO:
- 68;
- CDR1 is SEQ ID NO:
- 32, CDR2 is SEQ ID NO:
- 51, and CDR3 is SEQ ID NO:
- 69;
- CDR1 is SEQ ID NO:
- 30, CDR2 is SEQ ID NO:
- 48, and CDR3 is SEQ ID NO:
- 66;
- or
- CDR1 is SEQ ID NO:
- 23, CDR2 is SEQ ID NO:
- 41, and CDR3 is SEQ ID NO:
- 59;
- and
- wherein the polypeptide does not comprise an ISV that binds to matrix metalloproteinase 13 (MMP13).
A polypeptide comprising an immunoglobulin single variable domain (ISV) that specifically binds to Aggrecan, wherein the ISV that specifically binds Aggrecan essentially consists of 4 framework regions (FR1 to FR4, respectively) and 3 complementarity determining regions (CDR1 to CDR3, respectively), wherein:
- CDR1 has the amino acid sequence of the CDR1 of an ISVD comprising the amino acid sequence of SEQ ID NO:
- 118, CDR2 has the amino acid sequence of the CDR2 of an ISVD comprising the amino acid sequence of SEQ ID NO:
- 118, and CDR3 has the amino acid sequence of the CDR3 of an ISVD comprising the amino acid sequence of SEQ ID NO:
- 118;
- CDR1 has the amino acid sequence of the CDR1 of an ISVD comprising the amino acid sequence of SEQ ID NO:
- 13, CDR2 has the amino acid sequence of the CDR2 of an ISVD comprising the amino acid sequence of SEQ ID NO:
- 13, and CDR3 has the amino acid sequence of the CDR3 of an ISVD comprising the amino acid sequence of SEQ ID NO:
- 13;
- CDR1 has the amino acid sequence of the CDR1 of an ISVD comprising the amino acid sequence of SEQ ID NO:
- 4, CDR2 has the amino acid sequence of the CDR2 of an ISVD comprising the amino acid sequence of SEQ ID NO:
- 4, and CDR3 has the amino acid sequence of the CDR3 of an ISVD comprising the amino acid sequence of SEQ ID NO:
- 4;
- CDR1 has the amino acid sequence of the CDR1 of an ISVD comprising the amino acid sequence of SEQ ID NO:
- 11, CDR2 has the amino acid sequence of the CDR2 of an ISVD comprising the amino acid sequence of SEQ ID NO:
- 11, and CDR3 has the amino acid sequence of the CDR3 of an ISVD comprising the amino acid sequence of SEQ ID NO:
- 11;
- or
- CDR1 has the amino acid sequence of the CDR1 of an ISVD comprising the amino acid sequence of SEQ ID NO:
- 14, CDR2 has the amino acid sequence of the CDR2 of an ISVD comprising the amino acid sequence of SEQ ID NO:
- 14, and CDR3 has the amino acid sequence of the CDR3 of an ISVD comprising the amino acid sequence of SEQ ID NO:
- 14;
- wherein the CDRs are numbered according to the same antibody numbering system;
- and
- wherein the polypeptide does not comprise an ISV that binds to matrix metalloproteinase 13 (MMP13).
Dependencies are inferred from the claim text.