Mouse FcγammaRII-specific Fc antibody
AssigneeChugai Seiyaku Kabushiki Kaisha
InventorsTomoyuki Igawa, Eriko Murata, Futa Mimoto
Life of this patent
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Abstract
The present inventors have successfully found a large number of Fc variants with remarkably increased binding activity against and/or binding selectivity for mouse FcγRII by introducing amino acid alteration(s) to the Fc region.
Claims18
A polypeptide comprising a full-length Fc region that is a variant of a full-length, naturally occurring mouse Fc region, wherein the amino acid sequence of the variant Fc region differs from the amino acid sequence of the naturally occurring mouse Fc region at two to six positions, wherein the binding selectivity of the variant Fc region for mouse FcγRII relative to mouse FcγRIII is at least 5 times greater than that of the naturally occurring Fc region, wherein the amino acid at position 239 of the variant Fc region is Asp, and wherein at least one of the two to six positions of the variant Fc region is selected from the following group and is substituted with the indicated amino acid:
- position 230, substituted with Glu;
- position 231, substituted with Asp;
- position 232, substituted with Glu;
- and
- position 238, substituted with Glu (all positions by EU numbering).
A method of producing a polypeptide comprising a variant Fc region, the method comprising:
- selecting a first nucleotide sequence encoding a first polypeptide comprising a first Fc region, wherein the amino acid sequence of the first Fc region is identical to the amino acid sequence of a full-length, naturally occurring mouse Fc region;
- providing a nucleic acid molecule comprising a second nucleotide sequence encoding a second polypeptide comprising the variant Fc region, wherein the variant Fc region is a full-length Fc region that differs from the first Fc region at two to six positions;
- expressing the nucleic acid molecule in vitro, thereby producing the second polypeptide;
- and
- collecting the produced second polypeptide comprising the variant Fc region, wherein the binding selectivity of the second polypeptide for mouse FcγRII relative to mouse FcγRIII is at least 5 times greater than that of the first polypeptide, wherein the amino acid at position 239 is Asp, and wherein at least one of the two to six positions of the variant Fc region is selected from the following group and is substituted with the indicated amino acid:
- position 230, substituted with Glu;
- position 231, substituted with Asp;
- position 232, substituted with Glu;
- and
- position 238, substituted with Glu (all positions by EU numbering).
Dependencies are inferred from the claim text.