Assays for detecting antibodies specific to therapeutic anti-IgE antibodies and their use in anaphylaxis
AssigneeGenentech, Inc.
InventorsSaloumeh Fischer, Dana L. Baker, Henry B. Lowman, Gerald R. Nakamura
Life of this patent
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Abstract
The invention provides methods and reagents useful for detecting anti-drug antibodies of IgE isotype to therapeutic anti-IgE antibodies, and methods for assessing risk of anaphylaxis to administration of a therapeutic anti-IgE antibody.
Claims40
A method for detecting an anti-drug antibody of IgE isotype that may be present in a sample from a human patient, wherein variable regions of the anti-drug antibody specifically bind to a therapeutic anti-IgE antibody, comprising the steps of:
- (a) contacting the sample with a mutant of the therapeutic antibody comprising one, two, three, four, five, or six amino acid mutations in complementarity determining region (CDR) sequences of a heavy or light chain of the therapeutic anti-IgE antibody, wherein relative binding affinity of the mutant therapeutic antibody to an Fc region of human IgE is about 10% or less of relative binding affinity of the therapeutic anti-IgE antibody to said Fc region of human IgE;
- and
- (b) detecting specific binding of the anti-drug antibody of IgE isotype in the sample to the mutant therapeutic antibody, wherein the detection of the specific binding indicates presence or level of the anti-drug antibody of IgE isotype in the patient.
A method for detecting an anti-drug antibody of IgE isotype that may be present in a sample from a human patient, wherein variable regions of the anti-drug antibody specifically bind to a therapeutic anti-IgE antibody, comprising the steps of:
- (a) contacting the sample with a mutant of the therapeutic antibody comprising one, two, three, four, five, or six amino acid mutations in complementarity determining region (CDR) sequences of a heavy or light chain of the therapeutic anti-IgE antibody, wherein potency of the mutant therapeutic antibody to human IgE is about 10% or less of potency of the therapeutic anti-IgE antibody to said human IgE;
- and
- (b) detecting specific binding of the anti-drug antibody of IgE isotype in the sample to the mutant therapeutic antibody, wherein the detection of the specific binding indicates presence or level of the anti-drug antibody of IgE isotype in the patient.
A method for detecting an anti-drug antibody of IgE isotype that may be present in a sample from a human patient, wherein variable regions of the anti-drug antibody specifically bind to a therapeutic anti-IgE antibody, comprising the steps of:
- (a) contacting the sample that may contain the anti-drug antibody with (i) a mutant of the therapeutic antibody and (ii) an FcεRIα polypeptide that binds to an Fc region of a human IgE, wherein the mutant therapeutic antibody comprises one, two, three, four, five, or six amino acid mutations in complementarity determining region (CDR) sequences of a heavy or light chain of the therapeutic anti-IgE antibody, and wherein relative binding affinity of the mutant therapeutic antibody to an Fc region of human IgE is about 10% or less of relative binding affinity of the therapeutic anti-IgE antibody to said Fc region of human IgE;
- wherein the sample contains whole blood, serum or plasma from the human patient;
- (b) capturing the contacted mutant therapeutic antibody to a surface;
- and
- (c) detecting specific binding of the anti-drug antibody of IgE isotype in the sample to the mutant therapeutic antibody, wherein the detection of the specific binding indicates presence or level of the anti-drug antibody of IgE isotype in the patient.
Dependencies are inferred from the claim text.