Antibody variant combinations and uses thereof
AssigneeGenmab B.V.
InventorsRob De Jong, Frank Beurskens, Gijs Zom, Janine Schuurman, Xiaoguang Xue
Life of this patent
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Abstract
The invention relates to combination therapy involving two or more antibodies, wherein the Fc regions of the two antibodies have been modified such that hetero-oligomerization between the antibodies is strongly favored over self-oligomerization when antibodies are bound to their corresponding target antigens and such that hetero-oligomerization-independent effector functions of one or both antibodies are eliminated or strongly reduced. The invention also relates to antibodies, compositions, and kits suitable for use in the combination therapy of the invention.
Claims17
A method of treating cancer, the method comprising administering an effective amount of a first antibody comprising a first Fc region of a human IgG and a first antigen-binding region capable of binding to a first antigen and a second antibody comprising a second Fc region of a human IgG and a second antigen-binding region capable of binding to a second antigen,
- wherein said first Fc region comprises:
- a. a substitution at position E430, a substitution at position E345, or a combination of the substitutions K248E and T437R, and
- b. a K439E or S440K substitution,
- and said second Fc region comprises
- c. a substitution at position E430, a substitution at position E345, or a combination of the substitutions K248E and T437R, and
- d. a K439E or S440K substitution,
- wherein the first Fc region has a K439E substitution and the second Fc region has an S440K substitution, or the first Fc region has an S440K substitution and the second Fc region has a K439E substitution,
- wherein the first antibody and/or the second antibody does not comprise N-linked glycosylation at position N297, and
- wherein the amino acid positions correspond to human IgG1 according to the Eu numbering system.
Dependencies are inferred from the claim text.