Amino acid sequences directed against GPCRS and polypeptides comprising the same for the treatment of GPCR-related diseases and disorders
The present invention relates to amino acid sequences that are directed against G-protein coupled receptors (GPCRs), as well as to compounds or constructs, and in particular proteins and polypeptides, that comprise or essentially consist of one or more such amino acid sequences. The invention also relates to nucleic acids encoding such amino acid sequences and; to methods for preparing such amino acid sequences and polypeptides; to host cells expressing or capable of expressing such amino acid sequences or polypeptides; to compositions, and in particular to pharmaceutical compositions, that comprise such amino acid sequences, polypeptides, nucleic acids and/or host cells; and to uses of such amino acid sequences or polypeptides, nucleic acids, host cells and/or compositions, in particular for prophylactic, therapeutic or diagnostic purposes.
1. A polypeptide comprising two or more VHH sequences which specifically bind to a C—X—C chemokine receptor 7 (CXCR7), wherein
a) at least one first VHH sequence specifically binds a first epitope of CXCR7; and
b) at least one second VHH sequence specifically binds a second epitope of CXCR7,
wherein the first epitope is different from the second epitope of CXCR7, and
wherein the VHH sequences each comprise an amino acid sequence with the general structure FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4 in which FR1-FR4 refer to framework regions 1 to 4, respectively, and in which CDR1 to CDR3 refer to the complementary determining regions 1 to 3 respectively,
and wherein
c) the first VHH sequence comprises a CDR1 comprising the amino acid sequence of SEQ ID NO: 550, a CDR2 comprising the amino acid sequence of SEQ ID NO: 562, and a CDR3 comprising the amino acid sequence of SEQ ID NO: 574;
and
d) the second VHH sequence comprises a CDR1 comprising the amino acid sequence of SEQ ID NO: 551, a CDR2 comprising the amino acid sequence of SEQ ID NO: 563, and a CDR3 comprising the amino acid sequence of SEQ ID NO: 575.
2. The polypeptide according to claim 1 , wherein said polypeptide further comprises an amino acid sequence which binds serum albumin.
3. A pharmaceutical composition comprising a polypeptide according to claim 1 .
4. A compound or construct comprising a polypeptide according to claim 1 .