Rationally-designed anti-αβν6 integrin antibody MFEVP1 and variants thereof, method of making such antibody and the use thereof in treating and diagnosis of disease

摘要

The present invention relates to antibodies that are obtained by inserting an amino acid sequence capable of binding to a target into the complementarity determining region (CDR) of a parent antibody. The antibody thus obtained has a new binding specificity. For example, the antibodies of the present invention are able to bind to the target, such as αvβ6 integrin, while retaining one or more of the useful properties of the parent antibody.

主权项

1. An anti-αvβ6 integrin antibody obtained by inserting the amino acid sequence consisting of AVPNLRGDLQVLAQKVA (SEQ ID NO: 19) between adjacent amino acid residues Thr98 and Gly99 (in Kabat numbering) of CDR H3 of a parent antibody, wherein the parent antibody comprises the following complementarity determining regions (CDRs):
(a) Heavy Chain CDR 1: Asp Ser Tyr Met His (SEQ ID NO: 53); and (b) Heavy Chain CDR 2: Trp Ile Asp Pro Glu Asn Gly Asp Thr Glu Tyr Ala Pro Lys Phe Gln Gly (SEQ ID NO; 54); and (c) Heavy Chain CDR 3: (i) Gly Thr Pro Thr Gly Pro Tyr Tyr Phe Asp Tyr (SEQ ID NO: 55), or (ii) Gly Thr Pro Thr Gly Pro Tyr Pro Phe Asp Tyr (SEQ ID NO: 56); and (d) Light Chain CDR 1: (i) Ser Ala Ser Ser Ser Val Pro Tyr Met His (SEQ ID NO: 57), or (ii) Ser Ala Ser Ser Ser Val Ser Tyr Met His (SEQ ID NO: 58); and (e) Light Chain CDR 2: (i) Ser Thr Ser Asn Leu Ala Ser (SEQ ID NO: 59), or (ii) Leu Thr Ser Asn Leu Ala Ser (SEQ ID NO: 60); and (f) Light Chain CDR 3: Gln Gln Arg Ser Ser Tyr Pro Leu Thr (SEQ ID NO: 61).