Fc mutants
AssigneeThe Rockefeller University
InventorsJeffrey V. Ravetch, Rene G. Ott
Life of this patent
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Abstract
The present invention provides reagents, methods and systems for predicting the inhibitory activity of an antibody or variant thereof comprising: determining a binding affinity of the antibody or variant thereof to a Fc activating receptor; determining a binding affinity of the antibody or variant thereof to a Fc inhibitory receptor, and calculating the ratio of said activating binding affinity to said inhibitory binding affinity (A/I ratio), wherein the magnitude of said ratio is less than one (1).
Claims11
An amino acid sequence comprising
- a first fragment consisting of amino acids 215-396 of SEQ ID NO:
- 1, wherein in said fragment, amino acids corresponding to amino acids at positions 215, 326, 359, and 396 of SEQ ID NO:
- 1 are different from said amino acids present in SEQ ID NO:
- 1, or
- a second fragment consisting of amino acids 247-354 of SEQ ID NO:
- 1, wherein in said fragment, amino acids corresponding to amino acids at positions 247, 252, 266, 278, 302, and 354 of SEQ ID NO:
- 1 are different from said amino acids present in SEQ ID NO:
- 1, or
- a third fragment consisting of amino acids 211-399 of SEQ ID NO:
- 1, wherein in said fragment, amino acids corresponding to amino acids at positions 211, 243, 326, and 399 of SEQ ID NO:
- 1 are different from said amino acids present in SEQ ID NO:
- 1, or
- a fourth fragment consisting of amino acids 210-378 of SEQ ID NO:
- 1, wherein in said fragment, amino acids corresponding to amino acids at positions 210, 285, 326, 369, and 378 of SEQ ID NO:
- 1 are different from said amino acids present in SEQ ID NO:
- 1.
An amino acid sequence comprising
- a first fragment consisting of amino acids 215-396 of a heavy chain of an IgG, wherein in said first fragment, amino acids corresponding to amino acids at positions 215, 326, 359, and 396 of said heavy chain of the IgG are different from said amino acids present in said heavy chain of the IgG, and wherein the numbering is according to the EU index as in Kabat, or
- a second fragment consisting of amino acids 247-354 of a heavy chain of an IgG, wherein in said second fragment, amino acids corresponding to amino acids at positions 247, 252, 266, 278, 302, and 354 of said heavy chain of the IgG are different from said amino acids present in said heavy chain of the IgG, and wherein the numbering is according to the EU index as in Kabat, or
- a third fragment consisting of amino acids 211-399 of a heavy chain of an IgG, wherein in said third fragment, amino acids corresponding to amino acids at positions 211, 243, 326, and 399 of said heavy chain of the IgG are different from said amino acids present in said heavy chain of the IgG, and wherein the numbering is according to the EU index as in Kabat, or
- a fourth fragment consisting of amino acids 210-378 of a heavy chain of an IgG, wherein in said fourth fragment, amino acids corresponding to amino acids at positions 210, 285, 326, 369, and 378 of said heavy chain of the IgG are different from said amino acids present in said heavy chain of the IgG, and wherein the numbering is according to the EU index as in Kabat.
An antibody variant or immunoadhesin variant comprising a variant of human IgG Fc region, which comprises amino acid substitutions at:
- a) positions 215, 326, 359, and 396;
- b) positions 247, 252, 266, 278, 302, and 354;
- c) positions 211, 243, 326, and 399;
- or
- d) positions 210, 285, 326, 369, and 378,
- wherein the numbering of the residues in the IgG Fc region is that of the EU index as in Kabat and
- wherein the antibody variant is able to bind an antigen, and the immunoadhesin variant is able to bind a ligand or receptor.
Dependencies are inferred from the claim text.