Biological materials related to cxcr7

Abstract

The present invention relates to particular 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. In particular, the present invention provides immunoglobulin single variable domains inhibiting CXCR7 mediated tumour growth.

What is claimed is: 
     
         1 .- 2 . (canceled) 
     
     
         3 . An immunoglobulin single variable domain that can specifically displace SDF-1 and/or I-TAC on human CXCR7 (SEQ ID NO: 1) with an average Ki of less than 100 nM and/or an average SDF-1 and/or I-TAC displacement of 50% or more. 
     
     
         4 .- 9 . (canceled) 
     
     
         10 . The immunoglobulin single variable domain of  claim 3  that binds to amino acid residue M33, and optionally amino acid residue V32 and/or amino acid residue M37 in CXCR7 (SEQ ID NO: 1). 
     
     
         11 . The immunoglobulin single variable domain of  claim 3  that binds to amino acid residue W19, and optionally S23 and/or D25 of CXCR7 (SEQ ID NO: 1). 
     
     
         12 . A method comprising administering to a subject in need thereof a therapeutically effective amount of the immunoglobulin single variable domain according to  claim 3 , wherein the administration result in the reduction of tumour growth and/or treatment of cancer, preferably head and neck cancer or GBM. 
     
     
         13 . The immunoglobulin single variable domain of  claim 3 , 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, CDR2 and CDR3 are chosen from the group consisting of:
 (1) CDR1 chosen from the group consisting of:
 a) the immunoglobulin single variable domain of SEQ ID NO: 9, 
 b) immunoglobulin single variable domains that have at least 80% amino acid identity with the immunoglobulin single variable domain of SEQ ID NO: 9, and 
 c) immunoglobulin single variable domains that have 3, 2, or 1 amino acid difference with the immunoglobulin single variable domain of SEQ ID NO: 9, 
 and CDR2 chosen from the group consisting of: 
 d) the immunoglobulin single variable domain of SEQ ID NO: 19, 
 e) immunoglobulin single variable domains that have at least 80% amino acid identity with the immunoglobulin single variable domain of SEQ ID NO: 19, and 
 f) immunoglobulin single variable domains that have 3, 2, or 1 amino acid difference with the immunoglobulin single variable domain of SEQ ID NO: 19, 
 and CDR3 chosen from the group consisting of: 
 g) the immunoglobulin single variable domain of SEQ ID NO: 29, 
 h) immunoglobulin single variable domains that have at least 80% amino acid identity with the immunoglobulin single variable domain of SEQ ID NO: 29, and 
 i) immunoglobulin single variable domains that have 3, 2, or 1 amino acid difference with the immunoglobulin single variable domain of SEQ ID NO: 29; 
 
 (2) CDR1 chosen from the group consisting of:
 a) the immunoglobulin single variable domain of SEQ ID NO: 10, 
 b) immunoglobulin single variable domains that have at least 80% amino acid identity with the immunoglobulin single variable domain of SEQ ID NO: 10, and 
 c) immunoglobulin single variable domains that have 3, 2, or 1 amino acid difference with the immunoglobulin single variable domain of SEQ ID NO: 10, 
 
 and CDR2 chosen from the group consisting of:
 d) the immunoglobulin single variable domain of SEQ ID NO: 20, 
 e) immunoglobulin single variable domains that have at least 80% amino acid identity with the immunoglobulin single variable domain of SEQ ID NO: 20, and 
 f) immunoglobulin single variable domains that have 3, 2, or 1 amino acid difference with the immunoglobulin single variable domain of SEQ ID NO: 20, 
 
 and CDR3 chosen from the group consisting of:
 g) the immunoglobulin single variable domain of SEQ ID NO: 30, 
 h) immunoglobulin single variable domains that have at least 80% amino acid identity with the immunoglobulin single variable domain of SEQ ID NO: 30, and 
 i) immunoglobulin single variable domains that have 3, 2, or 1 amino acid difference with the immunoglobulin single variable domain of SEQ ID NO: 30; 
 
 (3) CDR1 chosen from the group consisting of:
 a) the immunoglobulin single variable domain of SEQ ID NO: 11, 
 b) immunoglobulin single variable domains that have at least 80% amino acid identity with the immunoglobulin single variable domain of SEQ ID NO: 11, and 
 c) immunoglobulin single variable domains that have 3, 2, or 1 amino acid difference with the immunoglobulin single variable domain of SEQ ID NO: 11, 
 
 and CDR2 chosen from the group consisting of:
 d) the immunoglobulin single variable domain of SEQ ID NO: 21, 
 e) immunoglobulin single variable domains that have at least 80% amino acid identity with the immunoglobulin single variable domain of SEQ ID NO: 21, and 
 f) immunoglobulin single variable domains that have 3, 2, or 1 amino acid difference with the immunoglobulin single variable domain of SEQ ID NO: 21, 
 
 and CDR3 chosen from the group consisting of:
 g) the immunoglobulin single variable domain of SEQ ID NO: 31, 
 h) immunoglobulin single variable domains that have at least 80% amino acid identity with the immunoglobulin single variable domain of SEQ ID NO: 31, and 
 i) immunoglobulin single variable domains that have 3, 2, or 1 amino acid difference with the immunoglobulin single variable domain of SEQ ID NO: 31, 
 
 (4) CDR1 chosen from the group consisting of:
 a) the immunoglobulin single variable domain of SEQ ID NO: 12, 
 b) immunoglobulin single variable domains that have at least 80% amino acid identity with the immunoglobulin single variable domain of SEQ ID NO: 12, and 
 c) immunoglobulin single variable domains that have 3, 2, or 1 amino acid difference with the immunoglobulin single variable domain of SEQ ID NO: 12, 
 
 and CDR2 chosen from the group consisting of:
 d) the immunoglobulin single variable domain of SEQ ID NO: 22, 
 e) immunoglobulin single variable domains that have at least 80% amino acid identity with the immunoglobulin single variable domain of SEQ ID NO: 22, and 
 f) immunoglobulin single variable domains that have 3, 2, or 1 amino acid difference with the immunoglobulin single variable domain of SEQ ID NO: 22, 
 
 and CDR3 chosen from the group consisting of:
 g) the immunoglobulin single variable domain of SEQ ID NO: 32, 
 h) immunoglobulin single variable domains that have at least 80% amino acid identity with the immunoglobulin single variable domain of SEQ ID NO: 32, and 
 i) immunoglobulin single variable domains that have 3, 2, or 1 amino acid difference with the immunoglobulin single variable domain of SEQ ID NO: 32, 
 
 (5) CDR1 chosen from the group consisting of:
 a) the immunoglobulin single variable domain of SEQ ID NO: 13, 
 b) immunoglobulin single variable domains that have at least 80% amino acid identity with the immunoglobulin single variable domain of SEQ ID NO: 13, and 
 c) immunoglobulin single variable domains that have 3, 2, or 1 amino acid difference with the immunoglobulin single variable domain of SEQ ID NO: 13, 
 
 and CDR2 chosen from the group consisting of:
 d) the immunoglobulin single variable domain of SEQ ID NO: 23, 
 e) immunoglobulin single variable domains that have at least 80% amino acid identity with the immunoglobulin single variable domain of SEQ ID NO: 23, and 
 f) immunoglobulin single variable domains that have 3, 2, or 1 amino acid difference with the immunoglobulin single variable domain of SEQ ID NO: 23, 
 
 and CDR3 chosen from the group consisting of:
 g) the immunoglobulin single variable domain of SEQ ID NO: 33, 
 h) immunoglobulin single variable domains that have at least 80% amino acid identity with the immunoglobulin single variable domain of SEQ ID NO: 33, and 
 i) immunoglobulin single variable domains that have 3, 2, or 1 amino acid difference with the immunoglobulin single variable domain of SEQ ID NO: 33; 
 
 (6) CDR1 chosen from the group consisting of:
 a) the immunoglobulin single variable domain of SEQ ID NO: 93, 
 b) immunoglobulin single variable domains that have at least 80% amino acid identity with the immunoglobulin single variable domain of SEQ ID NO: 93, and 
 c) immunoglobulin single variable domains that have 3, 2, or 1 amino acid difference with the immunoglobulin single variable domain of SEQ ID NO: 93, 
 
 and CDR2 chosen from the group consisting of:
 d) the immunoglobulin single variable domain of SEQ ID NO: 95, 
 e) immunoglobulin single variable domains that have at least 80% amino acid identity with the immunoglobulin single variable domain of SEQ ID NO: 95, and 
 f) immunoglobulin single variable domains that have 3, 2, or 1 amino acid difference with the immunoglobulin single variable domain of SEQ ID NO: 95, 
 
 and CDR3 chosen from the group consisting of:
 g) the immunoglobulin single variable domain of SEQ ID NO: 97, 
 h) immunoglobulin single variable domains that have at least 80% amino acid identity with the immunoglobulin single variable domain of SEQ ID NO: 97, and 
 i) immunoglobulin single variable domains that have 3, 2, or 1 amino acid difference with the immunoglobulin single variable domain of SEQ ID NO: 97; 
 
 (7) CDR1 chosen from the group consisting of:
 a) the immunoglobulin single variable domain of SEQ ID NO: 107, 
 b) immunoglobulin single variable domains that have at least 80% amino acid identity with the immunoglobulin single variable domain of SEQ ID NO: 107, and 
 c) immunoglobulin single variable domains that have 3, 2, or 1 amino acid difference with the immunoglobulin single variable domain of SEQ ID NO: 107, 
 
 and CDR2 chosen from the group consisting of:
 d) the immunoglobulin single variable domain of SEQ ID NO: 115, 
 e) immunoglobulin single variable domains that have at least 80% amino acid identity with the immunoglobulin single variable domain of SEQ ID NO: 115, and 
 f) immunoglobulin single variable domains that have 3, 2, or 1 amino acid difference with the immunoglobulin single variable domain of SEQ ID NO: 115, 
 
 and CDR3 chosen from the group consisting of:
 g) the immunoglobulin single variable domain of SEQ ID NO: 123, 
 h) immunoglobulin single variable domains that have at least 80% amino acid identity with the immunoglobulin single variable domain of SEQ ID NO: 123, and 
 i) immunoglobulin single variable domains that have 3, 2, or 1 amino acid difference with the immunoglobulin single variable domain of SEQ ID NO: 123; 
 
 (8) CDR1 chosen from the group consisting of:
 a) the immunoglobulin single variable domain of SEQ ID NO: 108, 
 b) immunoglobulin single variable domains that have at least 80% amino acid identity with the immunoglobulin single variable domain of SEQ ID NO: 108, and 
 c) immunoglobulin single variable domains that have 3, 2, or 1 amino acid difference with the immunoglobulin single variable domain of SEQ ID NO: 108, 
 
 and CDR2 chosen from the group consisting of:
 d) the immunoglobulin single variable domain of SEQ ID NO: 116, 
 e) immunoglobulin single variable domains that have at least 80% amino acid identity with the immunoglobulin single variable domain of SEQ ID NO: 116, and 
 f) immunoglobulin single variable domains that have 3, 2, or 1 amino acid difference with the immunoglobulin single variable domain of SEQ ID NO: 116, 
 
 and CDR3 chosen from the group consisting of:
 g) the immunoglobulin single variable domain of SEQ ID NO: 124, 
 h) immunoglobulin single variable domains that have at least 80% amino acid identity with the immunoglobulin single variable domain of SEQ ID NO: 124, and 
 i) immunoglobulin single variable domains that have 3, 2, or 1 amino acid difference with the immunoglobulin single variable domain of SEQ ID NO: 124; and 
 
 (9) CDR1 chosen from the group consisting of:
 a) the immunoglobulin single variable domain of SEQ ID NO: 110, 
 b) immunoglobulin single variable domains that have at least 80% amino acid identity with the immunoglobulin single variable domain of SEQ ID NO: 110, and 
 c) immunoglobulin single variable domains that have 3, 2, or 1 amino acid difference with the immunoglobulin single variable domain of SEQ ID NO: 110, 
 
 and CDR2 chosen from the group consisting of:
 d) the immunoglobulin single variable domain of SEQ ID NO: 118, 
 e) immunoglobulin single variable domains that have at least 80% amino acid identity with the immunoglobulin single variable domain of SEQ ID NO: 118, and 
 f) immunoglobulin single variable domains that have 3, 2, or 1 amino acid difference with the immunoglobulin single variable domain of SEQ ID NO: 118, 
 
 and CDR3 chosen from the group consisting of:
 g) the immunoglobulin single variable domain of SEQ ID NO: 126, 
 h) immunoglobulin single variable domains that have at least 80% amino acid identity with the immunoglobulin single variable domain of SEQ ID NO: 126, and 
 i) immunoglobulin single variable domains that have 3, 2, or 1 amino acid difference with the immunoglobulin single variable domain of SEQ ID NO: 126. 
 
 
     
     
         14 .- 21 . (canceled) 
     
     
         22 . The immunoglobulin single variable domain according to  claim 3 , wherein the framework regions (FRs) have a sequence identity of more than 80% with the FRs of SEQ ID NOs: 4 to 8, 92, 103, 104 or 106 (FR1), 14 to 18, 94, 111, 112 or 114 (FR2), 24 to 28, 96, 119, 120 or 122 (FR3), and/or 34 to 38, 98, 127, 128 or 130 (FR4). 
     
     
         23 . A polypeptide comprising an immunoglobulin single variable domain of  claim 3 . 
     
     
         24 . The polypeptide according to  claim 23 , wherein the immunoglobulin single variable domain is selected from the group consisting of immunoglobulin single variable domains that have an amino acid sequence with a sequence identity of more than 80% with the immunoglobulin single variable domains of SEQ ID NOs: 39 to 43, 91 or 99-102. 
     
     
         25 . The polypeptide according to  claim 23  and additionally comprising at least one human serum albumin binding immunoglobulin single variable domain and optionally comprising a linker selected from the group of linkers with SEQ ID NOs: 49 to 58. 
     
     
         26 . The polypeptide according to  claim 23  and additionally comprising ALB8 (SEQ ID NO: 2), and optionally comprising a linker selected from the group of linkers with SEQ ID NOs: 49 to 58. 
     
     
         27 . The polypeptide according to  claim 23 , wherein the polypeptide is selected from the group consisting of polypeptides that have an amino acid sequence with a sequence identity of more than 80% with the polypeptides of SEQ ID NOs: 44 to 48, 78 to 89 and 131 to 140. 
     
     
         28 . A construct chosen from the group consisting of:
 constructs comprising at least two ISVDs that bind to amino acid residue W19, and optionally S23 and/or D25 of CXCR7 (SEQ ID NO: 1), wherein said at least two ISVDs can be the same or different; and   constructs comprising at least two ISVDs that bind to and/or recognize amino acid residue M33, and optionally amino acid residue V32 and/or amino acid residue M37 in CXCR7 (SEQ ID NO: 1), wherein said at least two ISVDs can be the same or different.   
     
     
         29 . A method comprising administering to a subject in need thereof a therapeutically effective amount of the construct according to  claim 28 , wherein the administration results in reduction tumour growth and/or treatment of cancer, preferably head and neck cancer or GBM. 
     
     
         30 . (canceled) 
     
     
         31 . A pharmaceutical composition comprising
 an immunoglobulin single variable domain according to  claim 3 ;   and optionally a pharmaceutically acceptable excipient.   
     
     
         32 . A method comprising administering to a subject in need thereof a therapeutically effective amount of the immunoglobulin single variable domain according to  claim 3 , wherein the administration results in treatment of cancer, preferably head or neck cancer, GBM and/or inflammatory diseases. 
     
     
         33 . A method comprising administering to a subject in need thereof a therapeutically effective amount of the immunoglobulin single variable domain according to  claim 3 , wherein the administration results in treatment of rheumatoid arthritis. 
     
     
         34 . A method comprising administering to a subject in need thereof a therapeutically effective amount of the immunoglobulin single variable domain according to  claim 3 , wherein the administration results in treatment of multiple sclerosis. 
     
     
         35 . (canceled)