MODIFIED VARIABLE DOMAIN MOLECULES AND METHODS FOR PRODUCING THEM B

摘要

The present disclosure provides an isolated, engineered or non-naturally occurring protein comprising an antibody light chain variable domain (VL) which may comprise at least one negatively charged amino acid positioned between residues 49 to 56 according to the numbering system of Kabat, the protein capable of binding specifically to an antigen.

主权项

1. An isolated, engineered or non-naturally occurring protein comprising:
a) an antibody light chain variable domain (VL) comprising a negatively charged amino acid at two or more positions between residues 49 and 56 according to the numbering system of Kabat, the protein capable of specifically binding to an antigen; or b) (i) an antibody light chain variable domain (VL) comprising a negatively charged amino acid at one or more positions between residues 49 and 56 according to the numbering system of Kabat; and
(ii) an antibody heavy chain variable domain (VH) comprising a negatively charged amino acid at one or more positions selected from the group consisting of residues 28, 30, 31, 32, 33 and 35 according to the numbering system of Kabat, wherein the protein is capable of specifically binding to an antigen; or c) a modified antibody light chain variable domain (VL) capable of specifically binding to an antigen, wherein the VL comprises a negatively charged amino acid at one or more positions selected from the group consisting of residues 49, 51, 52, 53 and 56 according to the numbering system of Kabat, and wherein the unmodified form of the VL does not comprise the negatively charged amino acid(s); or d) a modified antibody light chain variable domain (VL) capable of specifically binding to an antigen, wherein the VL comprises a negatively charged amino acid at two or more positions between residues 49 and 56 according to the numbering system of Kabat, and wherein the unmodified form of the VL does not comprise two or more negatively charged amino acid(s) at the positions; or e) (i) a modified antibody light chain variable domain (VL) comprising a negatively charged amino acid at a position between residues 49 and 56 according to the numbering system of Kabat, wherein the unmodified form of the VL does not comprise a negatively charged amino acid at the position; and
(ii) a modified antibody heavy chain variable domain (VH) comprising a negatively charged amino acid at one or more positions selected from the group consisting of residues 28, 30, 31, 32, 33 and 35 according to the numbering system of Kabat, wherein the unmodified form of the VH does not comprise a negatively charged amino acid at the position, wherein the modified protein is capable of specifically binding to an antigen.