NOVEL CARBOHYDRATE ANTIBODIES, PHARMACEUTICAL COMPOSITIONS AND USES THEREOF

摘要

The present invention provides antibodies or the antigen-binding portion thereof to a tumor-associate carbohydrate antigen. Also disclosed herein are pharmaceutical compositions and methods for the inhibition of cancer cells in a subject in need thereof. The pharmaceutical compositions comprise an antibody or an antigen-binding portion thereof and at least one pharmaceutically acceptable carrier.

主权项

1. An antibody, or an antigen-binding portion thereof, that binds to a carbohydrate antigen and comprises a heavy chain variable region, wherein the heavy chain variable region comprises three complementarity determining regions (CDRs), CDR1, CDR2 and CDR3, having amino acid sequences about 90% to about 100% homologous to the amino acid sequence set forth in SEQ ID Nos: 1, 2 and 3, respectively;
wherein the antibody or the antigen-binding portion thereof comprises at least one of the following amino acid substitution: (a) amino acid residue 28 in CDR1 is substituted with a basic amino acid, a neutral amino acid that is not Serine or a hydrophobic amino acid, (b) amino acid residue 31 in CDR1 is substituted with a basic amino acid, (c) amino acid residue 57 in CDR2 is substituted with a neutral, a basic or a hydrophobic amino acid, (d) amino acid residue 63 in CDR2 is substituted with a neutral amino acid, a basic amino acid or a hydrophobic amino acid that is not Proline, and/or (e) amino acid residue 105 in CDR3 is substituted with a basic amino acid, a hydrophobic amino acid or a neutral amino acid.