IP Library › Granted Patent US 12,364,697
Granted Patent B2
US 12,364,697 · App. 17/839,215 · Granted Jul 22, 2025

G1T38 superior dosage regimes

Inventors: Andrew Beelen (Research Triangle Park, NC); Jay Copeland Strum (Hillsborough, NC)
Assignee: Pharmacosmos Holding A/S
A61K31/519A61K31/506
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,364,697
App. No.
17/839,215
Granted
Jul 22, 2025
Kind
B2
Abstract

A G1T38 human oral dosage regime that provides a (mean AUC(0-24),ss (h*ng/mL))/(dose (mg)) ratio of less than 5 and/or a (mean AUC(0-24),ss (h*ng/mL))/(Absolute Neutrophil Count (cells/mm3)) ratio on day 22 of dosing of not greater than 1.25.

Claims (20)

1. A dosing regime for treating a human with cancer, the dosing regime comprising oral administration of a solid dosage form comprising a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor compound of structure:

wherein the dosing regime provides a (mean AUC (0-24)ss (h*ng/mL))/(Absolute Neutrophil Count (cells/mm 3 )) ratio in humans of less than 1.25 on day 22 of dosing,

and wherein the solid dosage form is administered twice daily at a concentration of about 150 mg spaced about 12 hours apart.

2. The dosing regime of claim 1 , wherein the dosing regime provides a mean AUC (0-24)ss (h*ng/mL))/(Absolute Neutrophil Count (cells/mm 3 )) ratio in humans of less than 1.0.

3. The dosing regime of claim 1 , further comprising the administration of one or more additional therapeutic agents.

4. The dosing regime of claim 3 , wherein the cancer is HR+/HER2− breast cancer and the additional therapeutic agent is an anti-estrogen compound.

5. The dosing regime of claim 4 , wherein the anti-estrogen compound is selected from the group consisting of tamoxifen, raloxifene, fulvestrant, letrozole, anastrozole, and exemestane.

6. The dosing regime of claim 1 , wherein the dosing regime is administered for at least 24 weeks.

7. The dosing regime of claim 1 , wherein the cancer is a CDK4/6 replication dependent cancer.

8. The dosing regime of claim 1 , wherein the cancer is selected from the group consisting of breast cancer, non-small cell lung carcinoma, liver cancer, prostate cancer, hematological cancer, melanoma, colon cancer, pancreatic cancer, liposarcoma, and gastrointestinal stromal tumor (GIST).

9. The dosing regime of claim 1 , wherein the cancer is selected from the group consisting of HR+/HER2− breast cancer, HR−/HER2+ breast cancer, EGFR mutant non-small cell carcinoma, KRAS mutant non-small cell lung carcinoma, hepatocellular carcinoma, uterine cancer, castrate resistant prostate cancer, mantle cell lymphoma, marginal zone lymphoma, chronic lymphocytic leukemia, follicular lymphoma, diffuse large B-cell lymphoma, BRAF mutant melanoma, RAS mutant colorectal cancer, RAS mutant pancreatic cancer, and RAS mutant cholangiocarcinoma.

10. The dosing regime of claim 4 , wherein Compound II and the anti-estrogen compound are administered after endocrine therapy failure.

11. The dosing regime of claim 5 , wherein the anti-estrogen compound is fulvestrant.

12. The dosing regime of claim 5 , wherein the anti-estrogen compound is letrozole.

13. The dosing regime of claim 8 , wherein the cancer is liver cancer.

14. The dosing regime of claim 9 , wherein the cancer is hepatocellular carcinoma.

15. The dosing regime of claim 8 , wherein the cancer is a hematological cancer.

16. The dosing regime of claim 9 , wherein the cancer is diffuse large B-cell lymphoma.

17. The dosing regime of claim 8 , wherein the cancer is non-small cell lung carcinoma.

18. The dosing regime of claim 1 , wherein the solid dosage form is administered twice daily at a concentration of 150 mg spaced 12 hours apart.

Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 5, 2024
From: G1 THERAPEUTICS, INC.
To: PHARMACOSMOS A/S
Reel/Frame 069502/0150 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 5, 2024
From: PHARMACOSMOS A/S
To: PHARMACOSMOS HOLDING A/S
Reel/Frame 069502/0168 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 18, 2024
From: BEELEN, ANDREW; STRUM, JAY COPELAND
To: G1 THERAPEUTICS, INC.
Reel/Frame 069310/0208 →
Continuity (6)
Continuation 16924033 · Jul 8, 2020
Continuation PCTUS2019012720 · Jan 8, 2019
Provisional Application 62614952 · Jan 8, 2018
Provisional Application 62679575 · Jun 1, 2018
Provisional Application 62788017 · Jan 3, 2019
Related Publication 20230149406A1 · May 18, 2023
References Cited (258)
US 7855211B2 · Coates et al. · 2010 [cited by applicant]
US 8415355B2 · Brain et al. · 2013 [cited by applicant]
US 8598186B2 · Tavares et al. · 2013 [cited by applicant]
US 8598197B2 · Tavares et al. · 2013 [cited by applicant]
US 8691830B2 · Tavares et al. · 2014 [cited by applicant]
US 8822683B2 · Tavares et al. · 2014 [cited by applicant]
US 8829012B2 · Tavares et al. · 2014 [cited by applicant]
US 9102682B2 · Tavares et al. · 2015 [cited by applicant]
US 9260442B2 · Tavares et al. · 2016 [cited by applicant]
US 9259399B2 · Chen-Kiang et al. · 2016 [cited by applicant]
US 9464092B2 · Strum et al. · 2016 [cited by applicant]
US 9481691B2 · Tavares et al. · 2016 [cited by applicant]
US 9487530B2 · Strum et al. · 2016 [cited by applicant]
US 9499564B2 · Tavares et al. · 2016 [cited by applicant]
US 9527857B2 · Strum et al. · 2016 [cited by applicant]
US 9700557B2 · Caponigro et al. · 2017 [cited by applicant]
US 9717735B2 · Strum et al. · 2017 [cited by applicant]
US 9745316B2 · Tavares · 2017 [cited by applicant]
US 9856268B2 · Tavares et al. · 2018 [cited by applicant]
US 9931345B2 · Strum et al. · 2018 [cited by applicant]
US 9957276B2 · Tavares et al. · 2018 [cited by applicant]
US 10076523B2 · Strum et al. · 2018 [cited by applicant]
US 10085992B2 · Strum et al. · 2018 [cited by applicant]
US 10189849B2 · Tavares et al. · 2019 [cited by applicant]
US 10189850B2 · Tavares et al. · 2019 [cited by applicant]
US 10189851B2 · Tavares et al. · 2019 [cited by applicant]
US 10231969B2 · Strum et al. · 2019 [cited by applicant]
US 11357779B2 · Beelen · 2022 [cited by examiner]
US 20100105653A1 · Besong et al. · 2010 [cited by applicant]
US 20110224221A1 · Sharpless et al. · 2011 [cited by applicant]
US 20110224227A1 · Sharpless et al. · 2011 [cited by applicant]
US 20120100100A1 · Sharpless et al. · 2012 [cited by applicant]
US 20140037622A1 · Boshoff et al. · 2014 [cited by applicant]
US 20140107114A1 · Kim et al. · 2014 [cited by applicant]
US 20140274896A1 · Strum et al. · 2014 [cited by applicant]
US 20160220569A1 · Strum et al. · 2016 [cited by applicant]
US 20160310499A1 · Strum et al. · 2016 [cited by applicant]
US 20160332989A1 · Wu et al. · 2016 [cited by applicant]
US 20170209574A1 · Cao et al. · 2017 [cited by applicant]
US 20170224819A1 · Hamdy et al. · 2017 [cited by applicant]
US 20170296659A1 · Lebwohl et al. · 2017 [cited by applicant]
US 20170368036A1 · Hattersley et al. · 2017 [cited by applicant]
US 20180221378A1 · Strum et al. · 2018 [cited by applicant]
US 20180243304A1 · Caponigro et al. · 2018 [cited by applicant]
US 20180318305A1 · Harris et al. · 2018 [cited by applicant]
US 20180360840A1 · Strum et al. · 2018 [cited by applicant]
US 20180360841A1 · Strum et al. · 2018 [cited by applicant]
US 20190030034A1 · Strum et al. · 2019 [cited by applicant]
US 20190119292A1 · Tavares et al. · 2019 [cited by applicant]
US 20190151311A1 · Strum et al. · 2019 [cited by applicant]
US 20190175598A1 · Selvaraj et al. · 2019 [cited by applicant]
US 20190275049A1 · Goldberg et al. · 2019 [cited by applicant]
CN 106065016A1 · 2016 [cited by applicant]
JP 2013519698 · 2011 [cited by applicant]
TW 200633693A · 2006 [cited by applicant]
TW 201618774A · 2016 [cited by applicant]
WO WO2005094830A1 · 2005 [cited by applicant]
WO WO2006061712A2 · 2006 [cited by applicant]
WO WO2008079933A2 · 2008 [cited by applicant]
WO WO2009085185A1 · 2009 [cited by applicant]
WO WO2010012777A1 · 2010 [cited by applicant]
WO WO2010020675A1 · 2010 [cited by applicant]
WO WO2011101277A1 · 2011 [cited by applicant]
WO WO2011101409A1 · 2011 [cited by applicant]
WO WO2011101417A1 · 2011 [cited by applicant]
WO WO2012068381A2 · 2012 [cited by applicant]
WO WO2012129344A1 · 2012 [cited by applicant]
WO WO2013014448A1 · 2013 [cited by applicant]
WO WO2013148748A1 · 2013 [cited by applicant]
WO WO2014128588A1 · 2014 [cited by applicant]
WO WO2015061407A1 · 2015 [cited by applicant]
WO WO2015084892A1 · 2015 [cited by applicant]
WO WO2015095840A1 · 2015 [cited by applicant]
WO WO2015161285A1 · 2015 [cited by applicant]
WO WO2015161287A1 · 2015 [cited by applicant]
WO WO2015161288A1 · 2015 [cited by applicant]
WO WO2016024227A1 · 2016 [cited by applicant]
WO WO2016025650A1 · 2016 [cited by applicant]
WO WO2017160568A1 · 2017 [cited by applicant]
WO WO2017193141A1 · 2017 [cited by applicant]
WO WO2018089518A1 · 2018 [cited by applicant]
WO WO2018106729A1 · 2018 [cited by applicant]
WO WO2018156812A1 · 2018 [cited by applicant]
WO WO2018170447A1 · 2018 [cited by applicant]
WO WO2018183479A1 · 2018 [cited by applicant]
WO WO2018218633A1 · 2018 [cited by applicant]
WO WO2018223022A1 · 2018 [cited by applicant]
WO WO2018228990A1 · 2018 [cited by applicant]
WO WO2018231859A1 · 2018 [cited by applicant]
WO WO2018233620A1 · 2018 [cited by applicant]
WO WO2018237158A1 · 2018 [cited by applicant]
WO WO2019006393A1 · 2019 [cited by applicant]
WO WO2019026006A1 · 2019 [cited by applicant]
WO WO2019108589A1 · 2019 [cited by applicant]
Byrn, S. et al. Pharmaceutical Solids: A Strategic Approach to Regulatory Considerations. Pharmaceutical Research. 12(7):945-954(Jul. 1, 1995). [cited by applicant]
Kawaguchi et al. Drug and crystal polymorphism. Journal of Human Environmental Engineering, 4(2):310-317(2002). (Translation). [cited by applicant]
Oshima, H. Crystallization of Polymorphs and Pseudo-polymorphs and Its Control. Transition to Stability. Pharm Stage. 6(10):48-53(2007). (Translation). [cited by applicant]
Establishment of Specifications and Test Methods for New Drugs. Pharmaceutical Affairs Bureau. 568(May 1, 2001). (Translation). [cited by applicant]
Takada, N. API form screening and selection in drug discovery stage. Pharm Stage. 6(10):20-25(2007). (Translation). [cited by applicant]
Yamano, M. Approach to Crystal Polymorph in Process Research of New Drug. Journal of Synthetic Organic Chemistry. 65:907-913(2007). (Translation). [cited by applicant]
Wang, Zhijie et al. Phase II clinical study of platinum-containing regimen combined with Celebrex for first-line treatment of advanced non-small cell lung cancer; Chinese Journal of Lung Cancer, Issue 03, Jun. 20, 2008. [cited by applicant]
Aldrich. Kras Mutant Cell lines. (Jul. 10, 2018). https://www.cancer.gov/research/key-initiatives/ras/outreach/reference-reagents/cell-lines. [cited by applicant]
Barginear, M.F. & Budman, D.R. Trastuzumab-DM1: A review of the novel immuno-conjugate for HER2-overexpressing breast cancer. The Open Breast Cancer Journal, 2009; 1: 25-30. [cited by applicant]
Baughn, L.B. et al. A novel orally active small molecule potently induces G1 arrest in primary myeloma cells and prevents tumor growth by specific inhibition of cyclin-dependent kinase 4/6. Cancer Res, Aug. 1, 2006; 66(… [cited by applicant]
Bisi, J.E. et al. Preclinical Characterization of G1T28: A Novel CDK4/6 Inhibitor for Reduction of Chemotherapy-Induced Myelosuppression. Mol. Cancer Therap. (15)5: 783-793, Jan. 29, 2016. [cited by applicant]
Bisi, J.E. et al. Preclinical development of G1T38: A novel, potent and selective inhibitor of cyclin dependent kinases 4/6 for use as an oral antineoplastic in patients with CDK4/6 sensitive tumor, Oncotarget. 8(26), 4… [cited by applicant]
Blachly et al. Emerging Drug Profile: Cyclin-Dependent Kinase Inhibitors. Leuk Lymphoma. Oct. 2013; 54(10): 2133-2143. doi:10.3109/10428194.2013.783911. [cited by applicant]
Bonelli, M.A. et al. Combined inhibition of CDK 4/6 and PI3K/AKT/mTOR pathways induces a synergistic anti-tumor effect in malignant pleural mesothelioma cells. Neoplasia, 2017, 19(8), 637-648. [cited by applicant]
Bose et al. Cyclin-dependent kinase inhibitor therapy for hematologic malignancies. Expert Opin Investigating Drugs. Jun. 2013; 22(6): 723-738. doi:10.1517/13543784.2013.7. [cited by applicant]
Boss, D.S. et al. Safety, tolerability, pharmacokinetics and pharmacodynamics of the oral cyclin-dependent kinase inhibitor AZD5438 when administered at intermittent and continuous dosing schedules in patients with adva… [cited by applicant]
Bucher, N. & Britten, C.D. G2 checkpoint abrogation and checkpoint kinase-1 targeting in the treatment of cancer. Br J Cancer, Feb. 12, 2008; 98(3): 523-528. [cited by applicant]
Bulat, I. et al. G1T38, an oral CDK4/6 inhibitor, dosed continuously in combination with Fulvestrant for HR+breast cancer: Preliminary Phase 1b Results. Journals of Clinical Oncology 36, No. 15 suppl, 1061-1061, 4 pages… [cited by applicant]
Bulat, I. et al. G1T38, An Oral Cdk4/6 Inhibitor, Dosed Continuously in Combination with Fulvestrant for Hr+ breast cancer: Preliminary Phase 1b Results. Abstract #1061 (G1 Therapeutics Presentation). [cited by applicant]
Chou, A. et al. Tailored first-line and second-line CDK4-targeting treatment combinations in mouse models of pancreatic cancer. Gut, 2017; 0:1-14. Published online Oct. 28, 2017 doi:10.1136.gutjnl-2017-315144. [cited by applicant]
Menu, E. et al. A novel therapeutic combination using PD 0332991 and bortezomib: study in the 5T33MM myeloma model. Cancer Res, Jul. 15, 2008; 68(14): 5519-5523. [cited by applicant]
Mino, R.C. Crystalline Polymorphism of Organic Compounds. opics in Current Chemistry, Springer, berlin, DE, 1998, 198, 163-208; ISSN: 0340-1022; DOI: 10.1007/3-540-69178-2. [cited by applicant]
Mita, M.M. et al. Randomized Phase II trial of the cyclin-dependent kinase inhibitor dinaciclib (MK-7965) versus capecitabine in patients with advanced breast cancer. Clin. Breast Cancer, 2014; 14:169-176. [cited by applicant]
NCT01958021—Study of Efficacy and Safety of LEE011 in Postmenopausal Women With Advanced Breast Cancer. (Monaleesa-2), First posted Oct. 8, 2013. [cited by applicant]
NCT02079636—A Study of Abemaciclib (LY2835219) in Combination with Another Anticancer Drug in Participants with Lung Cancer (NSCLC); Mar. 6, 2014. [cited by applicant]
NCT02779751—A Study of Abemaciclib (LY2835219) in Participants with Non-Small Cell Lung Cancer or Breast Cancer; May 20, 2016. [cited by applicant]
NCT03041311—Carboplatin, Etoposide, and Atezolizumab with or without Trilaciclib; Jul. 26, 2019. [cited by applicant]
NCT03294694—Ribociclib + PDR001 in Breast Cancer and Ovarian Cancer; Sep. 27, 2017. [cited by applicant]
NCT02983071—G1T38, a CDK 4/6 Inhibitor, in Combination With Fulvestrant in Hormone Receptor-Positive, HER2-Negative Locally Advanced or Metastatic Breast Cancer. [cited by applicant]
NCT03455829—G1T38, a CDK 4/6 Inhibitor, in Combination With Osimertinib in EGFR-Mutant Non-Small Cell Lung Cancer. [cited by applicant]
O'Dwyer, et al. phase I dose escalation trial of a daily oral CDK 4/6 inhibitor PD-0332991. J Clin Oncol, 2007; 25(18S): 3550. [Abstract]. [cited by applicant]
Ottensmeier, et al. A Novel Phase II Trial of Ipilimumab, Carboplatin and Etoposide (ICE) for the First Line Treatment of Extensive Stage Small Cell Lung Cancer (SCLC). Annals of Oncology 25 (Supplement 4): iv511-iv516,… [cited by applicant]
Rader et al. Dual CDK4/CDK6 Inhibition Induces Cell Cycle Arrest and Senescence in Neuroblastoma. Clin Cancer Res., 2013, 19(22): 6173-82. [cited by applicant]
Roberts et al. Multiple Roles of Cyclin-Dependent Kinase 4/6 Inhibitors in Cancer Therapy. JNCI, 2012; 104(6):476-487. [cited by applicant]
Rocha Lima, C.M.S. et al. G1T28, a cyclin dependent kinase 4/6 inhibitor, in combination with etoposide and carboplatin for extensive stage small cell lung cancer (ES-SCLC): preliminary results. Cancer Research, 2016, 7… [cited by applicant]
Schwartz, G.K. et al. Phase I study of PD 0332991, a cyclin-dependent kinase inhibitor, administered in 3-week cycles (Schedule 2/1). Br J Cancer, Jun. 7, 2011; 104(12): 1862-1868. [cited by applicant]
Smith, B. et al. Single oral dose acute and subacute toxicity of a c-MET tyrosine kinase inhibitor and CDK 4/6 inhibitor combination drug therapy. Am J. Cancer Res., 2018, 8(1), 183-191. [cited by applicant]
Sorrentino, J.A. et al. G1T28, a novel CDK 4/6 inhibitor, protects murine hematopoietic stem and progenitor cells from cytotoxic chemotherapy. Cancer Research, 2015, 75(15), 941, XP002799586; & 106th Annual Meeting of t… [cited by applicant]
Sorrentino, J.A. et al. Trilaciclib (G1T28), a CDK 4/6 inhibitor, enhances the efficacy of combination therapy and immune checkpoint inhibitor treatment in preclinical models. Cancer Research, 2017, 77(13), Supplement 1… [cited by applicant]
Sorrentino, J.A. et al. Abstract 2824: G1T38, a novel, oral, potent and selective CDK 4/6 inhibitor for the treatment of Rb competent tumors. Cancer Research. 2016, 1-2; Apr. 16, 2016 (14_Supplement). Poster Presentatio… [cited by applicant]
Stice, J.P. et al. CDK4/6 Therapeutic Intervention and viable alternative to taxane in CRPC. Molecular Cancer Research, 2017, 15(6), 660-669, XP55457140. [cited by applicant]
Tan et al. Trilaciclib plus chemotherapy versus chemotherapy alone in patients with metastatic triple-negative breast cancer; a multicenter, randomized, open-label, phase 2 trial. Lancet Oncol., 2019; 209(11), 1587-1601. [cited by applicant]
Weiss et al. Myelopreservation with the CDK4/6 inhibitor Trilaciclib in patients with small-cell lung cancer receiving first-line chemotherapy: a phase Ib/randomized phase II trial. Annals of Oncology, 2019, 30: 1613-16… [cited by applicant]
Wood, A.C. et al. Dual ALK and CDK 4/6 inhibition demonstrates synergy against neuroblastoma. Clin. Cancer Res., 2017, 23(11), 2856-2868. [cited by applicant]
Zhou, J. et al. Palbociclib, a selective CDK 4/6 inhibitor, enhances the effect of selumetinib in RAS-driven non-small cell lung cancer. Cancer Letters, 2017, 408, 130-137. [cited by applicant]
US, 2023/0043305, A1, U.S. Appl. No. 17/683,146, Smith et al., Feb. 9, 2023. [cited by applicant]
U.S. Appl. No. 18/117,983, Strum, filed Mar. 6, 2023. [cited by applicant]
Singhal, D. et al. Drug polymorphism and dosage form design: a practical perspective, Advanced Drug Delivery Reviews. 56:33(2004). [cited by applicant]
U.S. Pat. No. 8,598,186, B2, U.S. Appl. No. 13/869,520, Tavares et al., Dec. 3, 2013. [cited by applicant]
U.S. Pat. No. 8,598,197, B2, U.S. Appl. No. 13/869,576, Tavares et al., Dec. 3, 2013. [cited by applicant]
U.S. Pat. No. 8,691,830, B2, U.S. Appl. No. 13/869,594, Tavares et al., Apr. 8, 2014. [cited by applicant]
U.S. Pat. No. 8,822,683, B2, U.S. Appl. No. 14/162,637, Tavares et al., Sep. 2, 2014. [cited by applicant]
U.S. Pat. No. 8,829,012, B2, U.S. Appl. No. 14/162,649, Tavares et al., Sep. 9, 2014. [cited by applicant]
U.S. Pat. No. 9,102,682, B2, U.S. Appl. No. 14/452,296, Tavares et al., Aug. 11, 2015. [cited by applicant]
U.S. Pat. No. 9,260,442, B2, U.S. Appl. No. 14/498,796, Tavares, Jan. 27, 2016. [cited by applicant]
U.S. Pat. No. 9,464,092, B2, U.S. Appl. No. 14/212,911, Strum et al., Oct. 11, 2016. [cited by applicant]
U.S. Pat. No. 9,481,691, B2, U.S. Appl. No. 14/712,630, Tavares et al., Nov. 1, 2016. [cited by applicant]
U.S. Pat. No. 9,487,530, B2, U.S. Appl. No. 14/212,430, Strum et al., Nov. 8, 2016. [cited by applicant]
U.S. Pat. No. 9,499,564, B2, U.S. Appl. No. 14/712,582, Tavares et al., Nov. 22, 2016. [cited by applicant]
U.S. Pat. No. 9,527,857, B2, U.S. Appl. No. 14/214,048, Strum et al., Dec. 27, 2016. [cited by applicant]
U.S. Pat. No. 9,717,735, B2, U.S. Appl. No. 14/690,180, Strum et al., Aug. 1, 2017. [cited by applicant]
U.S. Pat. No. 9,745,316, B2, U.S. Appl. No. 14/982,443, Tavares, Aug. 29, 2017. [cited by applicant]
U.S. Pat. No. 9,856,268, B2, U.S. Appl. No. 15/348,862, Tavares, Jan. 2, 2018. [cited by applicant]
U.S. Pat. No. 9,931,345, B2, U.S. Appl. No. 15/288,878, Strum et al., Apr. 3, 2018. [cited by applicant]
U.S. Pat. No. 9,957,276, B2, U.S. Appl. No. 15/348,770, Tavares et al., May 1, 2018. [cited by applicant]
U.S. Pat. No. 10,076,523, B2, U.S. Appl. No. 15/387,083, Strum et al., Sep. 18, 2018. [cited by applicant]
U.S. Pat. No. 10,085,992, B2, U.S. Appl. No. 15/342,990, Strum et al., Oct. 2, 2018. [cited by applicant]
U.S. Pat. No. 10,189,849, B2, U.S. Appl. No. 15/918,834, Tavares et al., Jan. 29, 2019. [cited by applicant]
U.S. Pat. No. 10,189,850, B2, U.S. Appl. No. 15/918,852, Tavares et al., Jan. 29, 2019. [cited by applicant]
U.S. Pat. No. 10,189,851, B2, U.S. Appl. No. 15/918,877, Tavares et al., Jan. 29, 2019. [cited by applicant]
U.S. Pat. No. 10,231,969, B2, U.S. Appl. No. 15/457,699, Strum, et al., Mar. 29, 2019. [cited by applicant]
U.S. Pat. No. 10,376,519, B2, U.S. Appl. No. 15/665,071, Strum, et al., Aug. 13, 2019 [cited by applicant]
U.S. Pat. No. 10,413,547, B2, U.S. Appl. No. 16/142,574, Strum, et al., Sep. 17, 2019. [cited by applicant]
U.S. Pat. No. 10,434,104, B2, U.S. Appl. No. 16/112,362, Strum, et al., Oct. 8, 2019. [cited by applicant]
U.S. Pat. No. 10,464,940, B2, U.S. Appl. No. 15/860,483, Tavares et al., Nov. 5, 2019. [cited by applicant]
U.S. Pat. No. 10,618,905, B2, U.S. Appl. No. 16/230,412, Strum, et al., Apr. 14, 2020. [cited by applicant]
U.S. Pat. No. 10,633,362, B2, U.S. Appl. No. 16/221,201, Strum, et al., Apr. 28, 2020. [cited by applicant]
U.S. Pat. No. 10,660,896, B2, U.S. Appl. No. 15/943,278, Strum, et al., May 26, 2020. [cited by applicant]
U.S. Pat. No. 10,654,831, B2, U.S. Appl. No. 16/230,388, Strum, et al., May 19, 2020. [cited by applicant]
U.S. Pat. No. 10,696,682, B2, U.S. Appl. No. 16/226,430, Tavares et al., Jun. 30, 2020. [cited by applicant]
U.S. Pat. No. 10,709,711, B2, U.S. Appl. No. 16/228,308, Strum et al., Jul. 14, 2020. [cited by applicant]
U.S. Pat. No. 10,829,490, B2, U.S. Appl. No. 16/230,396, Strum et al., Nov. 10, 2020. [cited by applicant]
U.S. Pat. No. 10,865,210, B2 , U.S. Appl. No. 16/230,381, Smith et al., Dec. 15, 2020. [cited by applicant]
U.S. Pat. No. 10,925,878, B2, U.S. Appl. No. 16/178,419, Strum et al., Feb. 23, 2021. [cited by applicant]
U.S. Pat. No. 10,927,120, B2, U.S. Appl. No. 16/721,631, Smith et al., Feb. 23, 2021. [cited by applicant]
U.S. Pat. No. 10,966,984, B2, U.S. Appl. No. 16/112,360, Strum et al., Apr. 6, 2021. [cited by applicant]
U.S. Pat. No. 10,981,887, B2, U.S. Appl. No. 16/824,290, Strum et al., Apr. 20, 2021. [cited by applicant]
U.S. Pat. No. 10,988,479, B2, U.S. Appl. No. 17/097,854, Schneider, Apr. 27, 2021. [cited by applicant]
U.S. Pat. No. 11,040,042, B2, U.S. Appl. No. 16/886,309, Strum et al., Jun. 22, 2021. [cited by applicant]
U.S. Pat. No. 11,090,306, A1, U.S. Appl. No. 16/572,418, Strum, et al., Aug. 17, 2021. [cited by applicant]
U.S. Pat. No. 11,261,193, A1, U.S. Appl. No. 16/721,631, Smith et al., Mar. 1, 2022. [cited by applicant]
U.S. Pat. No. 11,357,779, A1, U.S. Appl. No. 16/924,033, Beelen et al., Jun. 14, 2022. [cited by applicant]
U.S. Pat. No. 11,364,222, A1, U.S. Appl. No. 16/460,502, Strum et al., Jun. 21, 2022. [cited by applicant]
U.S. Pat. No. 11,395,821, A1, U.S. Appl. No. 16/547,342, Sorrentino, et al., Jul. 26, 2022. [cited by applicant]
U.S. Pat. No. 11,446,295, A1, U.S. Appl. No. 16/254,364, Strum, et al., Sep. 20, 2022. [cited by applicant]
U.S. Pat. No. 11,529,352, A1, U.S. Appl. No. 16/432,244, Sorrentino, et al., Dec. 20, 2022. [cited by applicant]
US, 2019/0167691, A1, U.S. Appl. No. 16/268,317, Strum, et al., Jun. 6, 2019. [cited by applicant]
US, 2020/0239486, A1, U.S. Appl. No. 16/847,426, Strum, et al., Jul. 30, 2020. [cited by applicant]
US, 2020/0283406, A1, U.S. Appl. No. 16/877,249, Strum, et al., Sep. 10, 2020. [cited by applicant]
US, 2020/0331925, A1, U.S. Appl. No. 16/918,985, Strum, et al., Oct. 22, 2020. [cited by applicant]
US, 2020/0345743, A1, U.S. Appl. No. 16/926,035, Strum, et al., Nov. 5, 2020. [cited by applicant]
US, 2021/0030758, A1, U.S. Appl. No. 17/067,549, Strum, et al., Feb. 4, 2021. [cited by applicant]
US, 2021/0047328, A1, U.S. Appl. No. 17/088,298, Strum, et al., Feb. 18, 2021. [cited by applicant]
US, 2021/0077498, A1, U.S. Appl. No. 17/102,311, Strum, et al., Mar. 18, 2021. [cited by applicant]
US, 2021/0122755, A1, U.S. Appl. No. 17/121,392, Smith et al., Apr. 29, 2021. [cited by applicant]
US, 2021/0213022, A1, U.S. Appl. No. 17/181,638, Strum, et al., Jul. 15, 2021. [cited by applicant]
US, 2021/0171554, A1, U.S. Appl. No. 17/176,962, Strum, et al., Jun. 10, 2021. [cited by applicant]
US, 2021/0179567, A1, U.S. Appl. No. 17/184,354, Schneider et al., Jun. 17, 2021. [cited by applicant]
US, 2021/0267986, A1, U.S. Appl. No. 17/315,011, Sorrentino et al., Sep. 2, 2021. [cited by applicant]
US, 2021/0387993, A1, U.S. Appl. No. 17/236,687, Schneider et al., Dec. 16, 2021. [cited by applicant]
US, 2021/0299130, A1, U.S. Appl. No. 17/222,873, Strum, et al., Sep. 30, 2021. [cited by applicant]
U.S. Appl. No. 17/683,146, Smith et al., filed Feb. 28, 2022. [cited by applicant]
U.S. Appl. No. 17/890,130, Strum et al., filed Aug. 17, 2022. [cited by applicant]
U.S. Appl. No. 17/854,755, Sorrentino et al., filed Jun. 30, 2022. [cited by applicant]
U.S. Appl. No. 17/898,196, Strum et al., filed Aug. 29, 2022. [cited by applicant]
U.S. Appl. No. 18/072,963, Sorrentino et al., filed Dec. 1, 2022. [cited by applicant]
US, 2023/0146638, A1, U.S. Appl. No. 17/854,755, Sorrentino et al., May 11, 2023. [cited by applicant]
U.S. Appl. No. 18/120,806, Tavares et al., filed Mar. 13, 2023. [cited by applicant]
Morissette, S.L. et al. High-through put crystallization: polymorphs, salts, cocrystals and solvates of pharmaceutical solids. Advanced Drug Delivery Reviews. 56:275-300(2004). [cited by applicant]
Shaw, A.T. et al. Alectinib in ALK-positive, crizotinib-resistant, non-small-cell lung cancer: a single-group, multicentre, phase 2 trial. Lancet Oncol. 17(2):234-242(Feb. 2016). Epub Dec. 19, 2015 (abstract). [cited by applicant]
Bisi, J.E. et al. Preclinical Characterization of G1T28: A Novel CDK4/6 Inhibitor for Reduction of Chemotherapy-Induced Myelosuppression. Mol. Cancer Therap. (2016) (15)5: 783-793. [cited by applicant]
Bisi, J.E. et al. Preclinical development of G1T38: A novel, potent and selective inhibitor of cyclin dependent kinases 4/6 for use as an oral antineoplastic in patients with CDK4/6 sensitive tumors. Oncotarget. 2017, 8… [cited by applicant]
Cross et al. AZD9291, an irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer. Cancer Discov. Sep. 2014; 4 (9): 1046-1061. doi:10.1158/2159-8290.CD-14-0337. [cited by applicant]
Deep, G. et al. New Combination Therapies with Cell Cycle Agents. Current Opinion in Investigational Drugs, 2008; 9(6), 591-605. [cited by applicant]
Deng et al. CDK4/6 Inhibition Augments Antitumor Immunity by Enhancing T-cell Activation. Cancer Discovery Feb. 2018. Published online Nov. 3, 2017; doi: 10.1158/2159-8290.CD-17-0915. [cited by applicant]
Dickson, M. et al. Phase II Trial of the CDK4 Inhibitor PD0332991 in Patients with Advanced CDK4-Amplified Well-Differentiated or Dedifferentiated Liposarcoma. J Clin Oncol. Jun. 1, 2013; 31(16): 2024-2028. [cited by applicant]
Finn et al. PD 0332991, a selective cyclin D kinase 4/6 inhibitor, preferentially inhibits proliferation of luminal estrogen receptor-positive human breast cancer cell lines in vitro. Breast Cancer Research, Oct. 29, 20… [cited by applicant]
Finn et al. Results of a randomized phase 2 study of PD 0332991, a cyclin-dependent kinase (CDK) 4/6 inhibitor, in combination with letrozole vs letrozole alone for first-line treatment of ER+/HER2-advanced breast cance… [cited by applicant]
Fry, D.W. et al. Specific inhibition of cyclin-dependent kinase 4/6 by PD 0332991 and associated antitumor activity in human tumor xenografts. Mol Cancer Ther., Nov. 2004; 3(11): 1427-1438. [cited by applicant]
Goel S. et al. Overcoming therapeutic resistance in HER2-positive breast cancers with CDK 4/6 inhibitors. Cancer Cell, 2016, 29, 255-269. [cited by applicant]
Goel, S. et al. CDK4/6 Inhibition Triggers Anti-Tumour Immunity. Nature, 2017, 548 (7668), 471-475. doi: 10.1038/nature23465. Epub Aug. 16, 2017. [cited by applicant]
Gojo, I. et al. Phase II study of the cyclin-dependent kinase (CDK) inhibitor dinaciclib (SCH 727965) in patients with advanced acute leukemias. ASH Annual Meeting Abstracts. 2010; 116: 3287. [cited by applicant]
Hamilton et al. Synergism of Cyclin-Dependent Kinase Inhibitors with Camptothecin Derivatives in Small Cell Lung Cancer Cell Lines. Molecules (2014), 19(2): 2077-2088. [cited by applicant]
Hamilton et al. Synergistic Anticancer Activity of Topotecan—Cyclin-Dependent Kinase Inhibitor Combinations against Drug-Resistant Small Cell Lung Cancer (SCLC) Cell Lines. Journal of Cancer Therapy (2013) 4: 47-53. [cited by applicant]
He et al. Transient CDK4/6 inhibition protects hematopoietic stem cells from chemotherapy-induced exhaustion. Science Translational Medicine, 2017, 9, eaal3986. [cited by applicant]
Janne et al. AZD9291 in EGFR Inhibitor-Resistant Non-Small-Cell Lung Cancer. N Engl J Med 2015; 372: 1689-99. DOI: 10.1056/NEJMoa1411817. [cited by applicant]
Johnson et al. Cyclin-dependent kinases (cdks) and the DNA damage response: rationale for cdk inhibitor-chemotherapy combinations as an anticancer strategy for solid tumors. Expert Opin Ther Targets, 2010, 14(11): 1199-… [cited by applicant]
Johnson, N. & Shapiro, G. Cyclin-dependent kinase 4/6 inhibition in cancer therapy. Cell Cycle, Nov. 1, 2012; 11(21): 3913-3918. [cited by applicant]
Kim, S. et al. The potent and selective cyclin-dependent kinases 4 and 6 inhibitor ribociclib (LEE011) is a versatile combination partner in preclinical cancer models. Oncotarget, 2018, 9(81), 35226-35240. [cited by applicant]
Liu et al. PD 0332991, a selective cyclin D kinase 4/6 inhibitor, sensitizes lung cancer cells to treatment with epidermal growth factor receptor tyrosine kinase inhibitors. Oncotarget, 2016, 7(51), pp. 84951-84964. [cited by applicant]
Caira, M.R. Crystalline Polymorphism of Organic Compounds. Topics in Current Chemistry. Design of Organic Solids. [cited by applicant]
U.S. Pat. No. 11,395,821, U.S. Appl. No. 16/547,342, Sorrentino et al., Jul. 26, 2022. [cited by applicant]
U.S. Pat. No. 11,629,150, B2, U.S. Appl. No. 17/121,392, Smith et al., Apr. 18, 2023. [cited by applicant]
U.S. Pat. No. 11,654,148, B2, U.S. Appl. No. 17/181,638, Strum et al., May 23, 2023. [cited by applicant]
U.S. Pat. No. 11,708,337, B2, U.S. Appl. No. 17/184,354, Schneider et al., Jul. 25, 2023. [cited by applicant]
U.S. Pat. No. 11,717,523, B2, U.S. Appl. No. 17/222,873, Strum et al., Aug. 8, 2023. [cited by applicant]
US, 2023/0241059, A1, U.S. Appl. No. 17/898,196, Strum et al., Aug. 3, 2023. [cited by applicant]
US, 2023/0248733, A1, U.S. Appl. No. 17/890,130, Strum et al., Aug. 10, 2023. [cited by applicant]
US, 2023/0302001, A1, U.S. Appl. No. 18/072,963, Sorrentino et al., Sep. 28, 2023. [cited by applicant]
US, 2023/0364098, A1, U.S. Appl. No. 18/117,983, Strum et al., Nov. 16, 2023. [cited by applicant]
US, 2023/0381189, A1, U.S. Appl. No. 18/231,091, Strum et al., Nov. 30, 2023. [cited by applicant]
US, 2024/0109906, A1, U.S. Appl. No. 18/120,806, Tavares et al., Apr. 4, 2024. [cited by applicant]
U.S. Appl. No. 18/225,537, Schneider et al., filed Jul. 24, 2023. [cited by applicant]
U.S. Pat. No. 12,139,494, B2, U.S. Appl. No. 17/683,146, Smith et al., Nov. 12, 2024. [cited by applicant]
U.S. Pat. No. 12,168,666, B2, U.S. Appl. No. 17/236,687, Schneider et al., Dec. 17, 2024. [cited by applicant]
US, 2022/0175780, A1, U.S. Appl. No. 17/403,577, Strum et al., Jun. 9, 2022. [cited by applicant]
US, 2022/0175787, A1, U.S. Appl. No. 17/554,940, Roberts et al., Jun. 9, 2022. [cited by applicant]
US, 2022/0241275, A1, U.S. Appl. No. 17/718,052, Strum et al., Aug. 4, 2022. [cited by applicant]
US, 2024/0139196, A1, U.S. Appl. No. 18/394,512, Beelen et al., May 2, 2024. [cited by applicant]
US, 2024/0199556, A1, U.S. Appl. No. 18/225,537, Schneider et al., Jul. 24, 2023. [cited by applicant]
U.S. Appl. No. 18/943,701, Smith et al., filed Nov. 11, 2024. [cited by applicant]
U.S. Appl. No. 18/957,373, Tavares et al., filed Nov. 22, 2024. [cited by applicant]
U.S. Appl. No. 18/973,646, Schneider et al., filed Dec. 9, 2024. [cited by applicant]
Xu, Binghe et al. “Lerociclib plus fulvestrant in patients with HR+/HER2-locally advanced or metastatic breast cancer who have progressed on prior endocrine therapy: Leonarda-1 a phase III randomized trial.” Nature Comm… [cited by applicant]
Cited By (3)
US 12,479,855 US 12,497,404 US 12,534,472