Claims for Patent: 9,181,162

Summary for Patent: 9,181,162

Title:	Compositions and methods for glucose transport inhibition
Abstract:	Glucose deprivation is an attractive strategy in cancer research and treatment. Cancer cells upregulate glucose uptake and metabolism for maintaining accelerated growth and proliferation rates. Specifically blocking these processes is likely to provide new insights to the role of glucose transport and metabolism in tumorigenesis, as well as in apoptosis. As solid tumors outgrow the surrounding vasculature, they encounter microenvironments with a limited supply of nutrients leading to a glucose deprived environment in some regions of the tumor. Cancer cells living in the glucose deprived environment undergo changes to prevent glucose deprivation-induced apoptosis. Knowing how cancer cells evade apoptosis induction is also likely to yield valuable information and knowledge of how to overcome the resistance to apoptosis induction in cancer cells. Disclosed herein are novel anticancer compounds that inhibit basal glucose transport, resulting in tumor suppression and new methods for the study of glucose deprivation in animal cancer research.
Inventor(s):	Chen; Xiaozhuo (Athens, OH), Bergmeier; Stephen (Athens, OH)
Assignee:	Ohio University (Athens, OH)
Application Number:	13/071,386
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 9,181,162
Patent Claims:	1. A basal glucose transport inhibitor compound of formula (III) or a salt thereof: ##STR00031## wherein R.sub.1 is selected from the group consisting of halo, alkyl, benzyl, amino, nitro, cyano, and alkoxy; wherein R.sub.2 is selected from the group consisting of hydrogen, halo, alkyl, benzyl, amino, nitro, cyano, and alkoxy; wherein R.sub.3 is selected from the group consisting of hydrogen, halo, alkyl, benzyl, amino, nitro, cyano, and alkoxy; wherein X is selected from the group consisting of --CH.sub.2--, --NH--, --NCH.sub.3--, and --O--; wherein Y is selected from the group consisting of --CH.sub.2--, --NH--, --NCH.sub.3--, and --O--; and wherein said basal glucose transport inhibitor compound of formula (III) or a salt thereof inhibits basal glucose transport when administered to a subject. 2. The basal glucose transport inhibitor compound according to claim 1, wherein the basal glucose transport inhibitor compound is selected from any one of: ##STR00032## or a salt thereof. 3. The basal glucose transport inhibitor compound of formula (III) or a salt thereof according to claim 1, wherein R.sub.1 is halo; wherein R.sub.2 is selected from hydrogen and alkyl; wherein R.sub.3 is selected from hydrogen and alkyl; wherein X is --NH--; and wherein Y is --NH--. 4. A method of treating cancer comprising: administering to a subject in need of such treatment a therapeutically effective amount of a basal glucose transport inhibitor compound of formula (III) or a pharmaceutically acceptable salt thereof: ##STR00033## wherein R.sub.1 is selected from the group consisting of halo, alkyl, benzyl, amino, nitro, cyano, and alkoxy; wherein R.sub.2 is selected from the group consisting of hydrogen, halo, alkyl, benzyl, amino, nitro, cyano, and alkoxy; wherein R.sub.3 is selected from the group consisting of hydrogen, halo, alkyl, benzyl, amino, nitro, cyano, and alkoxy; wherein X is selected from the group consisting of --CH.sub.2--, --NH--, --NCH.sub.3--, and --O--; wherein Y is selected from the group consisting of --CH.sub.2--, --NH--, --NCH.sub.3--, and --O--; and whereby administration of said basal glucose transport inhibitor compound of formula (III) or a pharmaceutically acceptable salt thereof to the subject treats said cancer by inhibiting basal glucose transport in said subject, and wherein the cancer is selected from lung cancer, colon cancer, melanoma, leukemia, ovarian cancer, renal cancer, prostate cancer, breast cancer, or a glioma. 5. The method of claim 4, wherein the cancer upregulates basal glucose transport. 6. The method of claim 4, wherein the basal glucose transport inhibitor compound of formula (III) or pharmaceutically acceptable salt thereof is administered via at least one of the following methods: oral, topical, intraarterial, intrapleural, intrathecal, intraventricular, subcutaneous, intraperitoneal, intraveneous, intravesicular, and gliadel wafers. 7. The method of claim 4, wherein the subject is a human. 8. The method of claim 4, further comprising administering to the subject in need of such treatment a second cancer drug. 9. The method of claim 8, wherein the second cancer drug is selected from the group consisting of methotrexate, doxorubicin hydrochloride, fluorouracil, everolimus, imiquimod, aldesleukin, alemtuzumab, pemetrexed disodium, palonosetron hydrochloride, chlorambucil, aminolevulinic acid, anastrozole, aprepitant, exemestane, nelarabine, arsenic trioxide, ofatumumab, bevacizumab, azacitidine, bendamustine hydrochloride, bexarotene, bleomycin, bortezomib, cabazitaxel, irinotecan hydrochloride, capecitabine, carboplatin, daunorubicin hydrochloride, cetuximab, cisplatin, cyclophosphamide, clofarabine, ifosfamide, cytarabine, dacarbazine, decitabine, dasatinib, degarelix, denileukin difitox, denosumab, dexrazoxane hydrochloride, docetaxel, rasburicase, epirubicin hydrochloride, oxaliplatin, eltrombopaq olamine, eribulin mesylate, erlotinib hydrochloride, etoposide phosphate, raloxifene hydrochloride, toremifane, fulvestrant, letrozole, filgrastim, fludarabim phosphate, pralatrexate, gefitinib, gemcitabine hydrochloride, gemcitibinecisplatin, gemtuzumab ozogamicin, imatinib mesylate, trastuzamab, topotecan hydrochloride, ibritumomab tiuxetan, romadepsin, ixabepilone, palifermin, lapatinib ditosylate, lenalidomide, leucovorin calcium, leuprolide acetate, liposomal procarbazine hydrochloride, temozolomide, plerixafor, acetidine, sorafenib tosylate, nilotinib, tamoxifen citrate, romiplostim, paclitaxel, pazopanib hydrochloride, pegaspargase, prednisone, procarbazine hydrochloride, proleukin, rituximab, romidepsin, Talc, sorafenic tosylate, sunitinib malate, thalidomide, temsirolimus, toremifene, trastuzumub, pantiumumab, vinblastine sulfate, vincristine, vorinostat, zoledronic acid, and any combination thereof. 10. The method of claim 4, wherein the basal glucose transport inhibitor compound is selected from any one of: ##STR00034## or a pharmaceutically acceptable salt thereof. 11. The method of claim 4, wherein R.sub.1 is halo; wherein R.sub.2 is selected from hydrogen and alkyl; wherein R.sub.3 is selected from hydrogen and alkyl; wherein X is --NH--; and wherein Y is --NH--.

Details for Patent 9,181,162

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Clinigen, Inc.	PROLEUKIN	aldesleukin	For Injection	103293	05/05/1992		2030-03-24
Amgen, Inc.	NEUPOGEN	filgrastim	Injection	103353	02/20/1991		2030-03-24
Amgen, Inc.	NEUPOGEN	filgrastim	Injection	103353	06/28/2000		2030-03-24
Servier Pharmaceuticals Llc	ONCASPAR	pegaspargase	Injection	103411	02/01/1994		2030-03-24
Genentech, Inc.	RITUXAN	rituximab	Injection	103705	11/26/1997		2030-03-24