Claims for Patent: 10,385,131

Summary for Patent: 10,385,131

Title:	Combination therapies of HDAC inhibitors and PD-L1 inhibitors
Abstract:	Provided herein are combinations that include an HDACi and a PD-L1 inhibitor that are useful for treating cancer, including cancer resistant to PD-1 inhibitors.
Inventor(s):	Bissonnette; Reid P. (Carlsbad, CA), Rolland; Alain (San Diego, CA), Gillings; Mireille (Winchester CDP, NV)
Assignee:	HUYA Bioscience International, LLC (San Diego, CA)
Application Number:	15/592,929
Patent Claims:	1. A method for treating cancer comprising administering a therapeutically effective amount of a histone deacetylase inhibitor (HDAC inhibitor) in combination with a PD-L1 inhibitor to a subject in need of treatment and whose cancer has been previously treated with a PD-1 inhibitor, wherein the PD-L1 inhibitor is an antibody PD-L1 inhibitor, and the HDAC inhibitor is a compound of formula I: ##STR00005## or a pharmaceutically acceptable salt thereof, wherein, A is phenyl or a heterocyclic group, optionally substituted with 1 to 4 substituents selected from the group consisting of halogen, --OH, --NH.sub.2, --NO.sub.2, --CN, --COOH, C.sub.1-C.sub.4 alkyl, C.sub.1-C.sub.4 alkoxy, C.sub.1-C.sub.4 aminoalkyl, C.sub.1-C.sub.4 alkylamino, C.sub.2-C.sub.4 acyl, C.sub.2-C.sub.4 acylamino, C.sub.1-C.sub.4 alkythio, C.sub.1-C.sub.4 perfluoroalkyl, C.sub.1-C.sub.4 perfluoroalkyloxy, C.sub.1-C.sub.4 alkoxycarbonyl, phenyl, and a heterocyclic group; B is phenyl optionally substituted with 1 to 3 substituents selected from the group consisting of halogen, --OH, --NH.sub.2, --NO.sub.2, --CN, --COOH, C.sub.1-C.sub.4 alkyl, C.sub.1-C.sub.4 alkoxy, C.sub.1-C.sub.4 aminoalkyl, C.sub.1-C.sub.4 alkylamino, C.sub.2-C.sub.4 acyl, C.sub.2-C.sub.4 acylamino, C.sub.1-C.sub.4 alkylthio, C.sub.1-C.sub.4 perfluoroalkyl, C.sub.1-C.sub.4 perfluoroalkyloxy, C.sub.1-C.sub.4 alkoxycarbonyl, and phenyl; Y is --C(O)NH--CH.sub.2--; Z is a bond or C.sub.1-C.sub.4 alkylene, --O--, --S--, --NH--, --CO--, --CS--, --SO--, or --SO.sub.2--; R.sup.1 and R.sup.2 are independently hydrogen or C.sub.1-C.sub.4 alkyl; R.sup.3 is hydrogen or C.sub.1-C.sub.4 alkyl; R.sup.4 is hydrogen or --NH.sub.2; one of X.sup.1, X.sup.2, X.sup.3, or X.sup.4 is halogen, --OH, --NH.sub.2, --NO.sub.2, --CN, --COOH, C.sub.1-C.sub.4 alkyl, C.sub.1-C.sub.4 alkoxy, C.sub.1-C.sub.4 aminoalkyl, C.sub.1-C.sub.4 alkylamino, C.sub.2-C.sub.4 acyl, C.sub.2-C.sub.4 acylamino, C.sub.1-C.sub.4 alkylthio, C.sub.1-C.sub.4 perfluoroalkyl, C.sub.1-C.sub.4 perfluoroalkyloxy, or C.sub.1-C.sub.4 alkoxycarbonyl optionally substituted with halogen or C.sub.1-C.sub.4 alkyl, while the others of X.sup.1, X.sup.2, X.sup.3, or X.sup.4 are independently hydrogen, provided, however, that when R.sup.4 is hydrogen, one of X.sup.1, X.sup.2, X.sup.3, or X.sup.4 is --NH.sub.2, an aminoalkyl group or an alkylamino group. 2. The method according to claim 1, wherein the cancer after treatment with PD-1 inhibitor resulted in partial response, but later develops resistance to PD-1 with progression of disease. 3. The method according to claim 1, wherein the cancer after treatment with PD-1 inhibitor resulted in stable disease, but later develops resistance to PD-1 with progression of disease. 4. The method according to claim 1, wherein the cancer after treatment with PD-1 inhibitor resulted in a complete response, but later develops resistance to PD-1 with progression of disease. 5. The method according to claim 1, wherein the cancer after treatment with PD-1 inhibitor resulted in no response to treatment. 6. The method according to claim 1, wherein the antibody PD-L1 inhibitor is durvalumab, avelumab, atezolizumab, BMS-936559, STI-A1010, STI-A1011, STI-A1012, STI-A1013, STI-A1014, or STI-A1015. 7. The method of claim 1, wherein the HDAC inhibitor is a compound of the following formula ##STR00006## 8. The method of claim 1, wherein the cancer treated is one or more of skin cancer, ovarian cancer; cancers of heart, placenta, and skeletal muscle; breast cancer; cancers of the head and neck, lymphomas, mantle cell lymphoma, non-Hodgkins B cell lymphoma, PTCL, adenoma, squamous cell carcinoma, laryngeal carcinoma, salivary carcinoma, thymomas and thymic carcinoma; leukemia; cancers of the retina; cancers of the esophagus; multiple myeloma; melanoma; colorectal cancer; lung cancer; cervical cancer; endometrium carcinoma; gallbladder cancer; liver cancer; thyroid follicular cancer; gastric cancer; non-small cell lung carcinoma; glioma; urothelial cancer; bladder cancer; prostate cancer; renal cell cancer; infiltrating ductal carcinoma; and glioblastoma multiform.

Details for Patent 10,385,131

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	TECENTRIQ	atezolizumab	Injection	761034	05/18/2016		2036-05-11
Genentech, Inc.	TECENTRIQ	atezolizumab	Injection	761034	03/08/2019		2036-05-11
Emd Serono, Inc.	BAVENCIO	avelumab	Injection	761049	03/23/2017		2036-05-11
Astrazeneca Uk Ltd	IMFINZI	durvalumab	Injection	761069	05/01/2017		2036-05-11