Methods and biomarkers for predicting efficacy and evaluation of an OX40 agonist treatment
AssigneeGenentech, Inc.
InventorMahrukh Huseni
Life of this patent
Estimating the term…
Abstract
The present disclosure provides methods for predicting responsiveness of a subject having cancer to an OX40 agonist treatment by measuring the expression level of one or more biomarkers. Also provided are methods for monitoring pharmacodynamic activity of or responsiveness to an OX40 agonist treatment by measuring the expression level of one or more biomarkers. Further provided are methods related thereto for treating or delaying progression of cancer in a subject by administering an effective amount of an OX40 agonist to a subject. Specific biomarkers for all such methods are described herein.
Claims13
A method for treating or delaying progression of cancer in a subject, comprising:
- (a) measuring the expression level of one or more marker genes in a sample comprising leukocytes obtained from the subject, wherein said one or more marker genes are selected from the group consisting of CD8a, CD8b, H2-d, CTLA4, CD64, CXCL9, IFNg, IDO1, GZMA, GZMB, PRF1, PDCA1, KLRK1, PTPRC, CXCL1, ITGAM, and IL7R;
- and
- (b) if the expression level of said one or more marker genes in the sample obtained from the subject is higher than a reference, administering to the subject an effective amount of an OX40 agonist;
- wherein the OX40 agonist is a monoclonal antibody that comprises:
- (1) HVR-H1 comprising the amino acid sequence of SEQ ID NO:2;
- (2) HVR-H2 comprising the amino acid sequence of SEQ ID NO:3;
- (3) HVR-H3 comprising the amino acid sequence of SEQ ID NO:4;
- (4) HVR-L1 comprising the amino acid sequence of SEQ ID NO:5;
- (5) HVR-L2 comprising the amino acid sequence of SEQ ID NO:6;
- and (6) HVR-L3 comprising the amino acid sequence of SEQ ID NO:7;
- or
- (1) HVR-H1 comprising the amino acid sequence of SEQ ID NO:29;
- (2) HVR-H2 comprising the amino acid sequence of SEQ ID NO:30;
- (3) HVR-H3 comprising the amino acid sequence of SEQ ID NO:33;
- (4) HVR-L1 comprising the amino acid sequence of SEQ ID NO:37;
- (5) HVR-L2 comprising the amino acid sequence of SEQ ID NO:39;
- and (6) HVR-L3 comprising the amino acid sequence of SEQ ID NO:42.
A method for treating or delaying progression of cancer in a subject, comprising administering to the subject an effective amount of an OX40 agonist, wherein a sample comprising leukocytes obtained from the subject has increased expression of one or more marker genes selected from the group consisting of CD8a, CD8b, H2-d, CTLA4, CD64, CXCL9, IFNg, IDOL GZMA, GZMB, PRF1, PDCA1, KLRK1, PTPRC, CXCL1, ITGAM, and IL7R, as compared with a reference;
- and wherein the OX40 agonist is a monoclonal antibody that comprises:
- (1) HVR-H1 comprising the amino acid sequence of SEQ ID NO:2;
- (2) HVR-H2 comprising the amino acid sequence of SEQ ID NO:3;
- (3) HVR-H3 comprising the amino acid sequence of SEQ ID NO:4;
- (4) HVR-L1 comprising the amino acid sequence of SEQ ID NO:5;
- (5) HVR-L2 comprising the amino acid sequence of SEQ ID NO:6;
- and (6) HVR-L3 comprising the amino acid sequence of SEQ ID NO:7;
- or
- (1) HVR-H1 comprising the amino acid sequence of SEQ ID NO:29;
- (2) HVR-H2 comprising the amino acid sequence of SEQ ID NO:30;
- (3) HVR-H3 comprising the amino acid sequence of SEQ ID NO:33;
- (4) HVR-L1 comprising the amino acid sequence of SEQ ID NO:37;
- (5) HVR-L2 comprising the amino acid sequence of SEQ ID NO:39;
- and (6) HVR-L3 comprising the amino acid sequence of SEQ ID NO:42.
Dependencies are inferred from the claim text.