Readily isolated bispecific antibodies with native immunoglobulin format
AssigneeRegeneron Pharmaceuticals, Inc.
InventorsSamuel Davis, Eric Smith, Douglas Macdonald, Kara Louise Olson
Life of this patent
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Abstract
A bispecific antibody format providing ease of isolation is provided, comprising immunoglobulin heavy chain variable domains that are differentially modified in the CH3 domain, wherein the differential modifications are non-immunogenic or substantially non-immunogenic with respect to the CH3 modifications, and at least one of the modifications results in a differential affinity for the bispecific antibody for an affinity reagent such as Protein A, and the bispecific antibody is isolable from a disrupted cell, from medium, or from a mixture of antibodies based on its affinity for Protein A.
Claims19
A method for making an antigen-binding protein, comprising:
- (a) culturing a cell containing
- (i) a first nucleic acid encoding a first immunoglobulin heavy chain comprising a first variable domain that recognizes a first epitope, wherein the first immunoglobulin heavy chain comprises a first CH3 region of a human IgG selected from IgG1, IgG2, and IgG4, wherein the first CH3 region binds to Protein A;
- (ii) a second nucleic acid encoding a second immunoglobulin heavy chain comprising a second variable domain that recognizes a second epitope, wherein the second immunoglobulin heavy chain comprises a second CH3 region of a human IgG selected from IgG1, IgG2, and IgG4, wherein the second CH3 region comprises a modification that reduces or eliminates binding of the second CH3 region to Protein A;
- (iii) a third nucleic acid encoding an immunoglobulin light chain that pairs with the first and the second immunoglobulin heavy chain;
- under conditions that allow the cell to express the first and the second immunoglobulin heavy chain and the immunoglobulin light chain to generate the antigen-binding protein, wherein the antigen-binding protein is heterodimeric with respect to Protein A binding;
- and,
- (b) isolating the antigen-binding protein from the cell using Protein A.
Dependencies are inferred from the claim text.