Anti-HER2 antibodies and their uses

摘要

The present disclosure relates to antibodies directed to HER2 and uses of such antibodies, for example to treat diseases associated with the activity and/or overproduction of HER2.

主权项

1. An anti-HER2 antibody or an anti-HER2 binding fragment of an antibody which comprises a VH having positions 1 to 117 of SEQ ID NO:1 and a VL having positions 1 to 103 of SEQ ID NO:2 that have one or more amino acid substitutions or combinations of amino acid substitutions as compared to an antibody having a VH comprising an amino acid sequence corresponding to positions 1 to 117 of SEQ ID NO:1 and a VL comprising an amino acid sequence corresponding to positions 1 to 103 of SEQ ID NO:2, wherein said one or more amino acid substitutions or combinations of amino acid substitutions are selected from:
(i) the third framework of the VH chain (FR-H3) substitution R83K as compared to a VH of SEQ ID NO: 1; (ii) the first CDR of the VL chain (CDR-L1) substitution D28L as compared to a VL of SEQ ID NO:2; (iii) the first CDR of the VL chain (CDR-L1) substitution A34D as compared to a VL of SEQ ID NO:2; (iv) the first CDR of the VL chain (CDR-L 1) substitution A34V as compared to a VL of SEQ ID NO:2; (v) the first CDR of the VH chain (CDR-H 1) substitution D31T as compared to a VH of SEQ ID NO: 1; (vi) the first CDR of the VH chain (CDR-H 1) substitution D31H as compared to a VH of SEQ ID NO: 1; (vii) the second CDR of the VH chain (CDR-H2) substitution Y52K as compared to a VH of SEQ ID NO: 1; and (viii) the third CDR of the VH chain (CDR-H3) substitution W95F as compared to a VH of SEQ ID NO: 1.