Biological materials related to c-Met
The present invention relates to biological materials related to c-Met possibly in combination with VEGF and/or EGFR, and more in particular to polypeptides, nucleic acids encoding such polypeptides; to methods for preparing such polypeptides; to host cells expressing or capable of expressing such polypeptides; to compositions and in particular to pharmaceutical compositions that comprise such polypeptides, for prophylactic, therapeutic or diagnostic purposes. Methods and kits for assessing the responsiveness of a patient to c-Met therapy are also described and provided.
1. A polypeptide consisting of an immunoglobulin single variable domain that can displace HGF from human c-Met (SEQ ID NO: 1), wherein the immunoglobulin single variable domain comprises an amino acid sequence with the formula 1
FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4 (1);
wherein FR1 to FR4 refer to framework regions 1 to 4 and are framework regions of an immunoglobulin single variable domain; and
wherein CDR1 is SEQ ID NO: 51; CDR2 is SEQ ID NO: 67; and CDR3 is SEQ ID NO: 83.
2. The polypeptide according to claim 1 , wherein the framework regions (FRs) have a sequence identity of more than 90% with the FRs of SEQ ID NO: 102.
3. A pharmaceutical composition comprising a polypeptide according to claim 1 ; and optionally a pharmaceutically acceptable excipient.
4. A kit for assessing the responsiveness of a patient suffering from a c-Met associated disease or disorder to a therapy, said kit comprising a polypeptide that can displace HGF from human c-Met (SEQ ID NO: 1) according to claim 1 and instructions for use.
5. A polypeptide comprising an immunoglobulin single variable domain that can displace HGF from human c-Met (SEQ ID NO: 1), wherein the immunoglobulin single variable domain comprises an amino acid sequence with the formula 1
FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4 (1);
wherein FR1 to FR4 refer to framework regions 1 to 4 and are framework regions of an immunoglobulin single variable domain; and
wherein CDR1 is SEQ ID NO: 51; CDR2 is SEQ ID NO: 67; and CDR3 is SEQ ID NO: 83.
6. The polypeptide according to claim 5 , wherein the polypeptide is selected from the group consisting of polypeptides that have an amino acid sequence with a sequence identity of more than 90% with SEQ ID NO: 102.
7. A fusion polypeptide comprising the immunoglobulin single variable domain of claim 5 fused to an immunoglobulin single variable domain that binds human serum albumin selected from the group consisting of, Alb11 (SEQ ID NO: 5) and Alb23 (SEQ ID NO: 101).
8. The fusion polypeptide according to claim 7 , wherein the polypeptide is selected from the group consisting of polypeptides that have an amino acid sequence with a sequence identity of more than 90% with SEQ ID NOs: 105, 106, 109, 110, 111, 113, or 188.
9. A pharmaceutical composition comprising a fusion polypeptide according to claim 7 ; and optionally a pharmaceutically acceptable excipient.
10. A kit for assessing the responsiveness of a patient suffering from a c-Met associated disease or disorder to a therapy, said kit comprising a fusion polypeptide that can displace HGF from human c-Met (SEQ ID NO: 1) according to claim 7 and instructions for use.
11. A pharmaceutical composition comprising a polypeptide according to claim 5 ; and optionally a pharmaceutically acceptable excipient.
12. A kit for assessing the responsiveness of a patient suffering from a c-Met associated disease or disorder to a therapy, said kit comprising a polypeptide that can displace HGF from human c-Met (SEQ ID NO: 1) according to claim 5 and instructions for use.