BIESPECIFIC BINDING MOLECULES ANG2 / VEGF

Claims

This description relates to bispecific binding molecules against human vascular endothelial growth factor (VEGF / VEGF-A) and against angiopoietin 2 (ANG2), including protein sequences, methods for their production, pharmaceutical compositions containing the bispecific binding molecules, and their uses. This description also relates to an anti-ANG2 heavy chain single-domain antibody and its application.

1. A multispecific molecule comprising a fusion protein characterized in that it comprises: (a) an angiopoietin 2 (ANG2) binding domain, (b) a vascular endothelial growth factor (VEGF) binding domain, and (c) a multimerization component; wherein the ANG2-binding domain comprises a VHH domain comprising three heavy chain complementarity-determining regions (HCDR1, HCDR2, and HCDR3) contained within a VH region comprising the amino acid sequence as set forth in SEQ ID No. 10, SEQ ID No. 11, SEQ ID No. 12, SEQ ID No. 13, SEQ ID No. 14, or SEQ ID No. 34, the VEGF-binding domain comprises one or more extracellular immunoglobulin (Ig)-like domains of one or more VEGF receptors (VEGFR), and the multimerization component comprises a polypeptide having a length of between 1 and 200 amino acids and having at least one cysteine ​​residue.

38. A pharmaceutical composition characterized in that it comprises the multi-specific molecule according to any one of the preceding claims, and one or more pharmaceutically acceptable vehicles.

39. An isolated polynucleotide encoding the multispecific molecule according to any one of claims 1-37.

40. A vector characterized in that it comprises the isolated polynucleotide according to claim 39.

41. A host expression system characterized in that it comprises the vector according to claim 40.

55. An anti-angiopoietin 2 (ANG2) antibody or its antigen-binding fragment characterized in that it comprises a VHH domain having three heavy chain complementarity-determining regions (HCDR1, HCDR2 and HCDR3) contained in a heavy chain variable region comprising the amino acid sequence set out in any one of SEQ ID No. 10-14, or any one of SEQ ID No. 19-42.

63. A pharmaceutical composition characterized in that it comprises the anti-ANG2 antibody or its antigen-binding fragment, according to any one of claims 55-62, and one or more pharmaceutically acceptable vehicles.

64. An isolated polynucleotide characterized in that it encodes the anti-ANG2 antibody or its antigen-binding fragment, according to any one of claims 55-62.

65. A vector characterized in that it comprises the isolated polynucleotide according to claim 64.

66. A host cell characterized in that it comprises the vector according to claim 65.

67. A method for expressing the anti-ANG2 antibody or its antigen-binding fragment, according to any one of claims 55-62, characterized in that it comprises culturing the host cell according to claim 66 under the conditions in which the vector is expressed according to claim 65.