Modified Fc-regions to enhance functional affinity of antibodies and antigen binding fragments thereof
AssigneeScancell Limited
InventorsLinda Gillian Durrant, Mireille Vankemmelbeke
Life of this patent
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Abstract
The present invention relates to the identification of key residues within mouse IgG3 antibodies (mAbs) that are responsible for intermolecular cooperativity and their transfer into IgG1 antibodies in order to enhance their functional affinity and direct a cell killing.
Claims15
A modified IgG1 antibody or antigen-binding fragment thereof comprising residues of an Fc-region of an immunoglobulin and a binding region, wherein residues of the Fc-region comprise N286, K288, K290, Q342, P343, E345, L351, T359, N361, Q362, G371, P374, S375, D376, and A378, numbered according to the IMGT system for the numbering of antibody sequences, are modified to the corresponding residue from a mouse IgG3 antibody, and wherein the modified IgG1 antibody or antigen-binding fragment thereof has enhanced when compared to a corresponding IgG1 antibody or antigen-binding fragment thereof comprising wildtype Fc-region residues.
A method of increasing the direct cell killing ability independent of the presence of complement or immune effector cells of an IgG1 antibody or antigen-binding fragment thereof comprising one or more residues of an Fc-region of an immunoglobulin and a binding region, wherein the method comprises replacing one or more residues of the CH2 and/or the CH3 domains of said Fc-region with one or more corresponding residues from mouse IgG3 CH2 and/or CH3 domains, and wherein the residues replaced with the corresponding residue from a mouse IgG3 antibody comprise N286, K288, K290, Q342, P343, E345, L351, T359, N361, Q362, G371, P374, S375, D376, and A378, numbered according to the IMGT system for the numbering of antibody sequences.
Dependencies are inferred from the claim text.