Combination therapy comprising ox40 binding agonists and tigit inhibitors
AssigneeGenentech, Inc.
InventorsJeong M. Kim, Jane L. Grogan
Life of this patent
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Abstract
The present invention describes combination therapy comprising an OX40 binding agonist and an agent that decreases or inhibits TIGIT expression and/or TIGIT activity and methods for use thereof, including methods of treating conditions where enhanced immunogenicity is desired, such as increasing tumor immunogenicity for the treatment of cancer or chronic infection.
Claims188
A method for treating or delaying progression of cancer in an individual comprising administering to the individual an effective amount of an OX40 binding agonist and an agent that decreases or inhibits TIGIT expression and/or activity.
A method for reducing or inhibiting cancer relapse or cancer progression in an individual comprising administering to the individual an effective amount of an OX40 binding agonist and an agent that decreases or inhibits TIGIT expression and/or activity.
A method for treating or delaying progression of an immune related disease in an individual comprising administering to the individual an effective amount of an OX40 binding agonist and an agent that decreases or inhibits TIGIT expression and/or activity.
A method for reducing or inhibiting progression of an immune related disease in an individual comprising administering to the individual an effective amount of an OX40 binding agonist and an agent that decreases or inhibits TIGIT expression and/or activity.
A method of increasing, enhancing, or stimulating an immune response or function in an individual comprising administering to the individual an effective amount of an OX40 binding agonist and an agent that decreases or inhibits TIGIT expression and/or activity.
A method of treating or delaying progression of cancer in an individual comprising administering to the individual an effective amount of an OX40 binding agonist and an agent that modulates CD226 expression and/or activity.
A method for reducing or inhibiting cancer relapse or cancer progression in an individual comprising administering to the individual an effective amount of an OX40 binding agonist and an agent that modulates CD226 expression and/or activity.
A method for treating or delaying progression of an immune related disease in an individual comprising administering to the individual an effective amount of an OX40 binding agonist and an agent that modulates CD226 expression and/or activity.
A method for reducing or inhibiting progression of an immune related disease in an individual comprising administering to the individual an effective amount of an OX40 binding agonist and an agent that modulates CD226 expression and/or activity.
A method of increasing, enhancing, or stimulating an immune response or function in an individual comprising administering to the individual an effective amount of an OX40 binding agonist and an agent that modulates CD226 expression and/or activity.
A method of increasing, enhancing, or stimulating an immune response or function in an individual comprising administering to the individual an effective amount of an OX40 binding agonist, an effective amount of an agent that decreases or inhibits TIGIT expression and/or activity, and an agent that decreases or inhibits one or more additional immune co-inhibitory receptors.
A method of increasing, enhancing, or stimulating an immune response or function in an individual comprising administering to the individual an effective amount of an OX40 binding agonist, an effective amount of an agent that decreases or inhibits TIGIT expression and/or activity, and an agent that increases or activates one or more additional immune co-stimulatory receptors or their ligands.
The method of any one of the preceding claims, further comprising administering at least one chemotherapeutic agent.
The method of any one of the preceding claims, wherein the individual has cancer.
The method of any one of the preceding claims, wherein CD4 and/or CD8 T cells in the individual have increased or enhanced priming, activation, proliferation, cytokine release, and/or cytolytic activity relative to prior to the administration of the combination.
The method of any one of the preceding claims, wherein the number of CD4 and/or CD8 T cells is elevated relative to prior to administration of the combination.
The method of any one of the preceding claims, wherein the number of activated CD4 and/or CD8 T cells is elevated relative to prior to administration of the combination.
The method of any one of the preceding claims, wherein activated CD4 and/or CD8 T cells are characterized by IFN-γ+ producing CD4 and/or CD8 T cells and/or enhanced cytolytic activity relative to prior to the administration of the combination.
The method of any one of the preceding claims, wherein the OX40 binding agonist is selected from the group consisting of an OX40 agonist antibody, an OX40L agonist fragment, an OX40 oligomeric receptor, and an OX40 immunoadhesin.
The method of any one of the preceding claims, wherein the depleting is by ADCC and/or phagocytosis.
The method of any one of the preceding claims, wherein the OX40 agonist antibody binds human OX40 with an affinity of less than or equal to about 0.45 nM.
The method of any one of the preceding claims, wherein the OX40 agonist antibody binds human OX40 and cynomolgus OX40.
The method of any one of the preceding claims, wherein the OX40 agonist antibody increases CD4+ effector T cell proliferation and/or increases cytokine production by the CD4+ effector T cell as compared to proliferation and/or cytokine production prior to treatment with the OX40 agonist antibody.
The method of any one of the preceding claims, wherein the OX40 agonist antibody increases memory T cell proliferation and/or increasing cytokine production by the memory cell.
The method of any one of the preceding claims, wherein the OX40 agonist antibody inhibits Treg function.
The method of any one of the preceding claims, wherein the OX40 agonist antibody increases OX40 signal transduction in a target cell that expresses OX40.
The method of any one of the preceding claims, wherein the OX40 agonist antibody is stable after treatment at 40° C. for two weeks.
The method of any one of the preceding claims, wherein the OX40 agonist antibody comprising a variant IgG1 Fe polypeptide comprising a mutation that eliminates binding to human effector cells has diminished activity relative to the OX40 agonist antibody comprising a native sequence IgG1 Fe portion.
The method of any one of the preceding claims, wherein antibody cross-linking is required for anti-human OX40 agonist antibody function.
The method of any one of the preceding claims, wherein the OX40 agonist antibody comprises (a) a VH domain comprising (i) HVR-H1 comprising the amino acid sequence of SEQ ID NO:
- 22, 28, or 29, (ii) HVR-H2 comprising the amino acid sequence of SEQ ID NO:
- 23, 30, 31, 32, 33 or 34, and (iii) HVR-H3 comprising an amino acid sequence selected from SEQ ID NO:
- 24, 35, or 39;
- and (iv) HVR-L1 comprising the amino acid sequence of SEQ ID NO:
- 25, (v) HVR-L2 comprising the amino acid sequence of SEQ ID NO:
- 26, and (vi) HVR-L3 comprising the amino acid sequence of SEQ ID NO:
- 27, 42, 43, 44, 45, 46, 47, or 48.
The method of any one of the preceding claims, wherein the OX40 agonist antibody comprises a VH sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO:
- 76, 78, 80, 82, 84, 86, 88, 90, 92, 94, 96, 98, 100, 102, 104, 106, 108, 110, 112, 114, 116, 118, 120, 128, 134, or 136.
The method of any one of the preceding claims, wherein the OX40 agonist antibody comprises a VL having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO:
- 77, 79, 81, 83, 85, 87, 89, 91, 93, 95, 97, 99, 101, 103, 105, 107, 109, 111, 113, 115, 117, 119, 121, 129, 135, or 137.
The method of any one of the preceding claims, wherein the OX40 agonist antibody comprises a VH sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO:
- 76.
The method of any one of the preceding claims, wherein the OX40 agonist antibody comprises a VL having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO:
- 77.
The method of any one of the preceding claims, wherein the OX40 agonist antibody comprises a VH sequence of SEQ ID NO:
- 76.
The method of any one of the preceding claims, wherein the OX40 agonist antibody comprises a VL sequence of SEQ ID NO:
- 77.
The method of any one of the preceding claims, wherein the OX40 agonist antibody comprises a VH sequence of SEQ ID NO:
- 76 and a VL sequence of SEQ ID NO:
- 77.
A kit comprising an OX40 binding agonist and a package insert comprising instructions for using the OX40 binding agonist in combination with an agent that decreases or inhibits TIGIT expression and/or activity to treat or delay progression of cancer in an individual.
A kit comprising an OX40 binding agonist and an agent that decreases or inhibits TIGIT expression and/or activity, and a package insert comprising instructions for using the OX40 binding agonist and the agent that decreases or inhibits TIGIT expression and/or activity to treat or delay progression of cancer in an individual.
A kit comprising an agent that decreases or inhibits TIGIT expression and/or activity and a package insert comprising instructions for using the agent that decreases or inhibits TIGIT expression and/or activity in combination with an OX40 binding agonist to treat or delay progression of cancer in an individual.
A kit comprising an OX40 binding agonist and a package insert comprising instructions for using the OX40 binding agonist in combination with an agent that decreases or inhibits TIGIT expression and/or activity to enhance immune function of an individual having cancer.
A kit comprising an OX40 binding agonist and an agent that decreases or inhibits TIGIT expression and/or activity, and a package insert comprising instructions for using the OX40 binding agonist and the agent that decreases or inhibits TIGIT expression and/or activity to enhance immune function of an individual having cancer.
A kit comprising an agent that decreases or inhibits TIGIT expression and/or activity and a package insert comprising instructions for using the agent that decreases or inhibits TIGIT expression and/or activity in combination with an OX40 binding agonist to enhance immune function of an individual having cancer.
A kit comprising an OX40 binding agonist and a package insert comprising instructions for using the OX40 binding agonist in combination with an agent that modulates CD226 expression and/or activity to treat or delay progression of cancer in an individual.
A kit comprising an OX40 binding agonist and an agent that modulates CD226 expression and/or activity, and a package insert comprising instructions for using the OX40 binding agonist and the agent that modulates CD226 expression and/or activity to treat or delay progression of cancer in an individual.
A kit comprising an agent that modulates CD226 expression and/or activity and a package insert comprising instructions for using the agent modulates 0D226 expression and/or activity in combination with an OX40 binding agonist to treat or delay progression of cancer in an individual.
A kit comprising an OX40 binding agonist and a package insert comprising instructions for using the OX40 binding agonist in combination with an agent that modulates CD226 expression and/or activity to enhance immune function of an individual having cancer.
A kit comprising an OX40 binding agonist and an agent that modulates CD226 expression and/or activity, and a package insert comprising instructions for using the OX40 binding agonist and the agent that modulates CD226 expression and/or activity to enhance immune function of an individual having cancer.
A kit comprising an agent modulates CD226 expression and/or activity and a package insert comprising instructions for using the agent that modulates CD226 expression and/or activity in combination with an OX40 binding agonist to enhance immune function of an individual having cancer.
Dependencies are inferred from the claim text.