Claims for Patent: 10,308,658

Summary for Patent: 10,308,658

Title:	Salt of EGFR inhibitor, crystalline form and uses thereof
Abstract:	The invention relates to a salt, a hydrate or a crystalline form of an EGFR inhibitor, and use thereof. Specifically it relates to 4-[(3-chloro-4-fluorophenyl)amino]-7-methoxy-6-[3-[(1R,6S)-2,5-dioxa-8-az- abicyclo [4.3.0] nonan-8-yl] propoxy] quinazoline dimethanesulfonate, hydrate and a crystalline form thereof; the invention also relates to a preparation method of the crystalline form disclosed herein, a pharmaceutical composition containing the crystalline form, and uses thereof for treating proliferative disorders.
Inventor(s):	Liu; Bing (Dongguan, CN), Zhang; Weihong (Dongguan, CN), Zhang; Yingjun (Dongguan, CN)
Assignee:	SUNSHINE LAKE PHARMA CO., LTD. (Dongguan, Guangdong, CN)
Application Number:	15/769,065
Patent Claims:	1. A compound having Formula (I): ##STR00005## 2. A hydrate of a compound having formula (I). ##STR00006## 3. The hydrate of claim 2, wherein the hydrate is a monohydrate of the compound having formula (I). 4. A crystalline form of a monohydrate of a compound having formula (I): ##STR00007## wherein the crystalline form is form I having one or more of following characteristics: i) an X-ray powder diffraction (XRPD) pattern comprising peaks expressed in degrees 2.theta. at 14.88.degree..+-.0.2.degree., 18.05.degree..+-.0.2.degree., 20.84.degree..+-.0.2.degree., 21.34.degree..+-.0.2.degree., 24.39.degree..+-.0.2.degree. and 25.18.degree..+-.0.2.degree.; or/and ii) the following structure parameters analyzed from monocrystalline: TABLE-US-00008 Crystallographic System: monoclinic system Space Groups: C2/c; Cell Parameters: a = 27.3004(5) .ANG., .alpha. = 90.degree., b = 16.2882(3) .ANG., .beta. = 103.3439(17).degree., c = 14.3529(2) .ANG., .gamma. = 90.degree.; Volume: 6210.01(18) .ANG..sup.3; Molecules number of 8. each unit cell (Z): 5. The crystalline form of claim 4 having an X-ray powder diffraction (XRPD) pattern comprising peaks expressed in degrees 2.theta. at 9.47.degree..+-.0.2.degree., 14.88.degree..+-.0.2.degree., 16.58.degree..+-.0.2.degree., 17.15.degree..+-.0.2.degree., 17.46.degree..+-.0.2.degree., 18.05.degree..+-.0.2.degree., 20.46.degree..+-.0.2.degree., 20.84.degree..+-.0.2.degree., 21.34.degree..+-.0.2.degree., 22.71.degree..+-.0.2.degree., 23.16.degree..+-.0.2.degree., 24.39.degree..+-.0.2.degree., 25.18.degree..+-.0.2.degree., 25.46.degree..+-.0.2.degree., 26.29.degree..+-.0.2.degree. and 28.01.degree..+-.0.2.degree.. 6. The crystalline form of claim 4 having an X-ray powder diffraction (XRPD) pattern comprising peaks expressed in degrees 2.theta. at 6.36.degree..+-.0.2.degree., 6.66.degree..+-.0.2.degree., 9.47.degree..+-.0.2.degree., 10.82.degree..+-.0.2.degree., 11.70.degree..+-.0.2.degree., 13.31.degree..+-.0.2.degree., 14.88.degree..+-.0.2.degree., 15.86.degree..+-.0.2.degree., 16.58.degree..+-.0.2.degree., 17.15.degree..+-.0.2.degree., 17.46.degree..+-.0.2.degree., 18.05.degree..+-.0.2.degree., 19.30.degree..+-.0.2.degree., 20.46.degree..+-.0.2.degree., 20.84.degree..+-.0.2.degree., 21.34.degree..+-.0.2.degree., 21.76.degree..+-.0.2.degree., 22.28.degree..+-.0.2.degree., 22.71.degree..+-.0.2.degree., 23.16.degree..+-.0.2.degree., 24.07.degree..+-.0.2.degree., 24.39.degree..+-.0.2.degree., 25.18.degree..+-.0.2.degree., 25.46.degree..+-.0.2.degree., 26.29.degree..+-.0.2.degree., 26.78.degree..+-.0.2.degree., 27.15.degree..+-.0.2.degree., 28.01.degree..+-.0.2.degree., 28.80.degree..+-.0.2.degree., 29.77.degree..+-.0.2.degree., 30.44.degree..+-.0.2.degree., 31.06.degree..+-.0.2.degree., 32.05.degree..+-.0.2.degree., 33.01.degree..+-.0.2.degree., 33.51.degree..+-.0.2.degree., 33.84.degree..+-.0.2.degree., 34.90.degree..+-.0.2.degree., 38.03.degree..+-.0.2.degree., 38.58.degree..+-.0.2.degree. and 39.48.degree..+-.0.2.degree.. 7. The crystalline form of claim 4 having an X-ray powder diffraction (XRPD) pattern as shown in FIG. 1. 8. The crystalline form of claim 4 having a monocrystalline structure as shown in FIG. 3. 9. A pharmaceutical composition comprising the compound of claim 1, and a pharmaceutically acceptable carrier, excipient, diluent, adjuvant, vehicle or a combination thereof. 10. The pharmaceutical composition of claim 9 further comprising a therapeutic agent, wherein the therapeutic agent is a chemotherapeutic agent used for treating proliferative disease or cancer, an antiproliferative agent, a cytotoxic agent, a signal transduction inhibitor, an agent used for treating non-small cell lung cancer or skin cancer or a combination thereof; and wherein the therapeutic agent is adriamycin, rapamycin, temsirolimus, everolimus, ixabepilone, gemcitabine, cyclophosphamide, dexamethasone, etoposide, fluorouracil, imatinib mesylate, dasatinib, nilotinib, erlotinib, lapatinib, gefitinib, sorafenib, sunitinib, interferon, carboplatin, topotecan, paclitaxel, vinblastine, vincristine, temozolomide, tositumomab, trabedectin, bevacizumab, trastuzumab, cetuximab, panitumumab, icotinib, icotinib hydrochloride, matuzmab, neratinib, canertinib, vandetanib, cediranib, vatalanib, axitinib, motesanib, nimotuzumab, theliatinib, epitinib, simotinib, poziotinib, varlitinib, rociletinib, pelitinib, osimertinib, PKI-166, PD 158780, MDX447, Mab425, HM-61713, TAS-121, seribantumab, naquotinib, or a combination thereof. 11. A method of inhibiting EGFR in a subject, comprising administering to the subject a therapeutically effective amount of the compound of claim 1. 12. A method of treating a proliferative disorder in a patient, comprising administering to the patient a therapeutically effective amount of the compound of claim 1; wherein the proliferative disorder is colon cancer lung cancer or malignant glioma. 13. A pharmaceutical composition comprising the hydrate of claim 2; and a pharmaceutically acceptable carrier, excipient, diluent, adjuvant, vehicle or a combination thereof. 14. A pharmaceutical composition comprising the crystalline form of claim 4; and a pharmaceutically acceptable carrier, excipient, diluent, adjuvant, vehicle or a combination thereof. 15. The pharmaceutical composition of claim 13 further comprising a therapeutic agent, wherein the therapeutic agent is a chemotherapeutic agent used for treating proliferative disease or cancer, an antiproliferative agent, a cytotoxic agent, a signal transduction inhibitor, an agent used for treating non-small cell lung cancer or skin cancer or a combination thereof; and wherein the therapeutic agent is adriamycin, rapamycin, temsirolimus, everolimus, ixabepilone, gemcitabine, cyclophosphamide, dexamethasone, etoposide, fluorouracil, imatinib mesylate, dasatinib, nilotinib, erlotinib, lapatinib, gefitinib, sorafenib, sunitinib, interferon, carboplatin, topotecan, paclitaxel, vinblastine, vincristine, temozolomide, tositumomab, trabedectin, bevacizumab, trastuzumab, cetuximab, panitumumab, icotinib, icotinib hydrochloride, matuzmab, neratinib, canertinib, vandetanib, cediranib, vatalanib, axitinib, motesanib, nimotuzumab, theliatinib, epitinib, simotinib, poziotinib, varlitinib, rociletinib, pelitinib, osimertinib, PKI-166, PD 158780, MDX447, Mab425, HM-61713, TAS-121, seribantumab, naquotinib, or a combination thereof. 16. The pharmaceutical composition of claim 14 further comprising a therapeutic agent, wherein the therapeutic agent is a chemotherapeutic agent used for treating proliferative disease or cancer, an antiproliferative agent, a cytotoxic agent, a signal transduction inhibitor, an agent used for treating non-small cell lung cancer or skin cancer or a combination thereof; and wherein the therapeutic agent is adriamycin, rapamycin, temsirolimus, everolimus, ixabepilone, gemcitabine, cyclophosphamide, dexamethasone, etoposide, fluorouracil, imatinib mesylate, dasatinib, nilotinib, erlotinib, lapatinib, gefitinib, sorafenib, sunitinib, interferon, carboplatin, topotecan, paclitaxel, vinblastine, vincristine, temozolomide, tositumomab, trabedectin, bevacizumab, trastuzumab, cetuximab, panitumumab, icotinib, icotinib hydrochloride, matuzmab, neratinib, canertinib, vandetanib, cediranib, vatalanib, axitinib, motesanib, nimotuzumab, theliatinib, epitinib, simotinib, poziotinib, varlitinib, rociletinib, pelitinib, osimertinib, PKI-166, PD 158780, MDX447, Mab425, HM-61713, TAS-121, seribantumab, naquotinib, or a combination thereof. 17. A method of inhibiting EGFR in a subject, comprising administering to the subject a therapeutically effective amount of the crystalline form of claim 4. 18. A method of inhibiting EGFR in a subject, comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition of claim 14. 19. A method of treating the severity of a proliferative disorder in a patient, comprising administering to the patient a therapeutically effective amount of the crystalline form of claim 4, wherein the proliferative disorder is colon cancer lung cancer, or malignant glioma. 20. A method of treating a proliferative disorder in a patient, comprising administering to the patient a therapeutically effective amount of the pharmaceutical composition of claim 14; wherein the proliferative disorder is colon cancer, lung cancer, or malignant glioma.

Details for Patent 10,308,658

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	09/25/1998		2035-10-19
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	02/10/2017		2035-10-19
Eli Lilly And Company	ERBITUX	cetuximab	Injection	125084	02/12/2004		2035-10-19
Eli Lilly And Company	ERBITUX	cetuximab	Injection	125084	03/28/2007		2035-10-19
Genentech, Inc.	AVASTIN	bevacizumab	Injection	125085	02/26/2004		2035-10-19