Multi-specific polypeptide complex targeting gprc5d
AssigneeChimagen Biosciences, Ltd.
InventorsZhenhao ZHOU, Jie ZHANG, Gong WANG, Xiaoqing WANG, Xiaoqin ZHANG, Qi WANG, Sainan SHI
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Abstract
The present invention discloses a multi-specific polypeptide complex, an isolated polynucleotide encoding the same, a pharmaceutical composition comprising the same, and use thereof.
Claims80
A multi-specific polypeptide complex, comprising a first antigen binding domain and a second antigen binding domain, wherein at least one of the first antigen binding domain and the second antigen binding domain binds to GPRC5D and comprises a GPRC5D binding domain;
- the GPRC5D binding domain comprises three heavy chain complementarity determining regions HCDR1, HCDR2, and HCDR3, and three light chain complementarity determining regions LCDR1, LCDR2, and LCDR3;
- and the heavy chain complementarity determining regions are identical to three heavy chain complementarity determining regions comprised in a heavy chain variable region (VH) as shown in SEQ ID NO:
- 13, and the light chain complementarity determining regions are identical to three light chain complementarity determining regions comprised in a light chain variable region (VL) as shown in SEQ ID NO:
- 12.
The polypeptide complex according to any one of preceding claims, wherein in the GPRC5D binding domain,
- a) the HCDR1 comprises the amino acid sequence as shown in SEQ ID NO:
- 4 or a variant thereof having no more than 3, 2 or 1 amino acid substitution, the HCDR2 comprises the amino acid sequence as shown in SEQ ID NO:
- 5 or a variant thereof having no more than 3, 2 or 1 amino acid substitution, the HCDR3 comprises the amino acid sequence as shown in SEQ ID NO:
- 6 or a variant thereof having no more than 3, 2 or 1 amino acid substitution, the LCDR1 comprises the amino acid sequence as shown in SEQ ID NO:
- 1 or a variant thereof having no more than 3, 2 or 1 amino acid substitution, the LCDR2 comprises the amino acid sequence as shown in SEQ ID NO:
- 2 or a variant thereof having no more than 3, 2 or 1 amino acid substitution, and the LCDR3 comprises the amino acid sequence as shown in SEQ ID NO:
- 3 or a variant thereof having no more than 3, 2 or 1 amino acid substitution;
- or
- b) the HCDR1 comprises the amino acid sequence as shown in SEQ ID NO:
- 9 or a variant thereof having no more than 3, 2 or 1 amino acid substitution, the HCDR2 comprises the amino acid sequence as shown in SEQ ID NO:
- 10 or a variant thereof having no more than 3, 2 or 1 amino acid substitution, the HCDR3 comprises the amino acid sequence as shown in SEQ ID NO:
- 11 or a variant thereof having no more than 3, 2 or 1 amino acid substitution, the LCDR1 comprises the amino acid sequence as shown in SEQ ID NO:
- 7 or a variant thereof having no more than 3, 2 or 1 amino acid substitution, the LCDR2 comprises the amino acid sequence as shown in SEQ ID NO:
- 8 or a variant thereof having no more than 3, 2 or 1 amino acid substitution, and the LCDR3 comprises the amino acid sequence as shown in SEQ ID NO:
- 3 or a variant thereof having no more than 3, 2 or 1 amino acid substitution.
The polypeptide complex according to any one of preceding claims, wherein in the GPRC5D binding domain, the heavy chain variable region comprises the amino acid sequence as shown in SEQ ID NO:
- 13 or a variant thereof having no more than 3, 2 or 1 amino acid substitution, and the light chain variable region comprises the amino acid sequence as shown in SEQ ID NO:
- 12 or a variant thereof having no more than 3, 2 or 1 amino acid substitution.
The polypeptide complex according to any one of preceding claims, wherein the GPRC5D binding domain is humanized.
The polypeptide complex according to any one of preceding claims, wherein the GPRC5D binding domain comprises a heavy chain variable region (VH) and/or a light chain variable region (VL);
- and
- a) the heavy chain variable region comprises an amino acid sequence selected from the group consisting of SEQ ID NO:
- 15, SEQ ID NO:
- 17, SEQ ID NO:
- 19, and SEQ ID NO:
- 21, or a variant thereof having no more than 3, 2 or 1 amino acid substitution;
- and
- b) the light chain variable region comprises an amino acid sequence selected from the group consisting of SEQ ID NO:
- 14, SEQ ID NO:
- 16, SEQ ID NO:
- 18, and SEQ ID NO:
- 20, or a variant thereof having no more than 3, 2 or 1 amino acid substitution.
The polypeptide complex according to any one of preceding claims, wherein the GPRC5D binding domain comprises a heavy chain variable region (VH) and/or a light chain variable region (VL);
- and
- a) the heavy chain variable region comprises the amino acid sequence as shown in SEQ ID NO:
- 15 or a variant thereof having no more than 3, 2 or 1 amino acid substitution, and the light chain variable region comprises the amino acid sequence as shown in SEQ ID NO:
- 14 or a variant thereof having no more than 3, 2 or 1 amino acid substitution;
- b) the heavy chain variable region comprises the amino acid sequence as shown in SEQ ID NO:
- 17 or a variant thereof having no more than 3, 2 or 1 amino acid substitution, and the light chain variable region comprises the amino acid sequence as shown in SEQ ID NO:
- 16 or a variant thereof having no more than 3, 2 or 1 amino acid substitution;
- c) the heavy chain variable region comprises the amino acid sequence as shown in SEQ ID NO:
- 19 or a variant thereof having no more than 3, 2 or 1 amino acid substitution, and the light chain variable region comprises the amino acid sequence as shown in SEQ ID NO:
- 18 or a variant thereof having no more than 3, 2 or 1 amino acid substitution;
- or
- d) the heavy chain variable region comprises the amino acid sequence as shown in SEQ ID NO:
- 21 or a variant thereof having no more than 3, 2 or 1 amino acid substitution, and the light chain variable region comprises the amino acid sequence as shown in SEQ ID NO:
- 20 or a variant thereof having no more than 3, 2 or 1 amino acid substitution,
- wherein the amino acid substitution does not occur in the CDR region.
The polypeptide complex according to any one of preceding claims, further comprising an immunoglobulin constant region, optionally a human immunoglobulin constant region, or optionally a human IgG constant region.
The polypeptide complex according to any one of preceding claims, wherein the other one of the first antigen binding domain and the second antigen binding domain binds to an antigen other than GPRC5D.
The polypeptide complex according to any one of claims 35 to 37, wherein the first antigen binding domain comprises the Her2 binding domain as defined in any one of claims 39 to 40, the second antigen binding domain comprises the CD3 binding domain as defined in any one of claims 15 to 16, and the third antigen binding domain comprises the antigen binding fragment of an antibody binding to GPRC5D according to any one of claims 1 to 10.
Dependencies are inferred from the claim text.