Granted Patent
B2
US 12,582,599 · App. 17/811,296 · Granted Mar 24, 2026
Methods for treatment of bladder cancer with gemcitabine
Assignee:
TARIS Biomedical LLC
View Patent ↗
Loading inventors, assignments & file history…
Abstract
Drug delivery devices and methods are provided for administering gemcitabine to a patient in need of treatment of bladder cancer by intravesically administering gemcitabine into the bladder of the patient to achieve a sustained concentration of the gemcitabine in urine in the bladder sufficient to produce a therapeutically effective concentration of the gemcitabine in the tissues of the bladder. In embodiments, the local administration into the patient's bladder is at a mean average amount of from 1 mg/day to about 300 mg/day of the gemcitabine (FBE).
Claims (13)
1 . A method for treating non-muscle invasive bladder cancer (NMIBC) in a human patient, comprising:
administering from 10 mg/day to 50 mg/day of gemcitabine free base equipment (FBE) continuously to the bladder of the human patient over a treatment period of 21 days by deploying into the human patient's bladder an intravesical drug delivery device which comprises the gemcitabine and urea;
wherein the intravesical drug delivery device comprises a housing that is elastically deformable between a retention shape configured to retain the intravesical drug delivery device in the bladder and a deployment shape for passage of the intravesical drug delivery device through a urethra,
wherein the housing comprises a predefined release aperture and a drug reservoir, the drug reservoir having a first region and a second region that is a distinct space from the first region,
wherein the gemcitabine is located in the first region in the form of one or more gemcitabine minitablets, and wherein the urea is located in the second region in the form of one or more urea minitablets;
wherein the treatment does not comprise a therapeutic agent other than gemcitabine;
releasing the gemcitabine from the predefined release aperture by osmotic pressure generated by the urea minitablets and into urine in the human patient's bladder,
and
wherein the human patient has not responded to Bacile Calmette-Guerin (BCG) treatment or wherein the human patient experienced adverse effects leading to discontinuation of BCG treatment.
2 . The method of claim 1 , wherein the housing contains and controls the release of the gemcitabine.
3 . The method of claim 2 , wherein the predefined release aperture is in communication with the drug reservoir.
4 . The method of claim 1 , wherein the intravesical drug delivery device is deployed into the human patient's bladder after a transurethral resection of bladder tumors (TURBT).
5 . The method of claim 1 , wherein the intravesical drug delivery device is deployed into the human patient's bladder before a transurethral resection of bladder tumors (TURBT).
Assignments (1)
MERGER
Recorded May 12, 2026
From: TARIS BIOMEDICAL LLC
To: JANSSEN BIOTECH, INC.
Reel/Frame 074630/0343 →
Continuity (4)
Provisional Application
61949215
· Mar 6, 2014
References Cited (217)
US 4008719A
· Theeuwes et al.
· 1977
[cited by applicant]
US 4111203A
· Theeuwes
· 1978
[cited by examiner]
US 6171298B1
· Masuura et al.
· 2001
[cited by applicant]
US 8343516B2
· Daniel et al.
· 2013
[cited by applicant]
US 8679094B2
· Cima et al.
· 2014
[cited by applicant]
US 8690840B2
· Lee et al.
· 2014
[cited by applicant]
US 8721621B2
· Boyko et al.
· 2014
[cited by applicant]
US 8801694B2
· Lee et al.
· 2014
[cited by applicant]
US 9017312B2
· Lee et al.
· 2015
[cited by applicant]
US 9107816B2
· Lee et al.
· 2015
[cited by applicant]
US 9457176B2
· Lee et al.
· 2016
[cited by applicant]
US 9539303B2
· McCulloch et al.
· 2017
[cited by applicant]
US 9586035B2
· Cima et al.
· 2017
[cited by applicant]
US 9636488B2
· Giesing
· 2017
[cited by applicant]
US 20040260272A1
· Friedman et al.
· 2004
[cited by applicant]
US 20100003297A1
· Tobias et al.
· 2010
[cited by applicant]
US 20110218488A1
· Boyko et al.
· 2011
[cited by applicant]
US 20140056986A1
· Desai
· 2014
[cited by applicant]
US 20150005595A1
· Tepper et al.
· 2015
[cited by applicant]
US 20150216937A1
· Wen
· 2015
[cited by applicant]
US 20150250717A1
· Giesing
· 2015
[cited by applicant]
US 20190388338A1
· Giesing
· 2019
[cited by applicant]
US 20220117886A1
· Giesing et al.
· 2022
[cited by applicant]
EP 1913962A1
· 2008
[cited by applicant]
RU 2591946C2
· 2016
[cited by applicant]
WO 2006030431A2
· 2006
[cited by applicant]
WO 2009139984A2
· 2009
[cited by applicant]
WO 2010151893A1
· 2010
[cited by applicant]
WO 2011031855A2
· 2011
[cited by applicant]
WO 2011089604A2
· 2011
[cited by applicant]
WO 2012048114A1
· 2012
[cited by applicant]
WO 2012096985A1
· 2012
[cited by applicant]
WO 2012106714A1
· 2012
[cited by applicant]
WO 2013148337A1
· 2013
[cited by applicant]
WO 2013170069A1
· 2013
[cited by applicant]
WO 2014036555A1
· 2014
[cited by applicant]
WO 2014036556A2
· 2014
[cited by applicant]
WO 2014144066A1
· 2014
[cited by applicant]
WO 2014145638A1
· 2014
[cited by applicant]
WO 2015026813A1
· 2015
[cited by applicant]
WO 2015069723A1
· 2015
[cited by applicant]
WO 2015134911A1
· 2015
[cited by applicant]
WO 2015200752A1
· 2015
[cited by applicant]
WO 2017193098A1
· 2017
[cited by applicant]
WO 2019023388A1
· 2019
[cited by applicant]
WO 2019094517A1
· 2019
[cited by applicant]
WO 2020028554A1
· 2020
[cited by applicant]
Laquente; “Antiangiogenic effect of gemcitabine follownig metronomic administration in a pancrease cancer model,” 2008; American Assn. Cancer, Molecular Cancer Therapeutics, vol. 7, No. 3, pp. 638-647. (Year: 2008).
[cited by examiner]
Shelly; “Intravesical gemcitabine therapy for non-mucle invasive bladder cancer (NMIBC): a systemic review,” 2012; BJU International; Cochrane Review, vol. 109, pp. 496-505. (Year: 2012).
[cited by examiner]
Merck Index entry for gemcitabine (M5690); p. 1. (Year: 2013).
[cited by examiner]
Hertel et al.; “Synthesis and Biological Activity of 2′,2′-Difluorodeoxycytidine (Gemcitabine),”—Ojima et al.; Biomedical Frontiers of Fluorine Chemistry, Chapter 19, pp. 265-278 (ACS Symposium Series, vol. 639, 1996). …
[cited by examiner]
Gontero et al.; “The Impact of Intravesical Gemcitabine and 1/3 Dose Bacillus Calmette-Guerin Instillation Therapy on the Quality of Life in Patients with Nonmuscle Invasive Bladder Cancer: Results of a Prospective, Ran…
[cited by examiner]
Giannantoni et al.; “New Frontiers in Intravesical Therapies and Drug Delivery,” 2006; European Assn. of Urology; European Urology, vol. 50, pp. 1183-1193. (Year: 2006).
[cited by examiner]
Merck Index entry for lidocaine (M6805), pp. 1-2. (Year: 2013).
[cited by examiner]
Khaled; “Primary chemotherapy with low-dose prolonged infusion gemcitabine and cisplatin in patients with bladder cancer: A Phase II trial,” 2008; Elsevier, Urologic Oncology: Seminars and Investigations, vol. 26, pp. 1…
[cited by examiner]
Mendelsohn et al.; “Bladder cancers arise from distinct urothelial sub-populations,” 2014, NPG; Nature Cell Biology, vol. 16, No. 10, pp. 982-991 and S1-S5 (16-pages). (Year: 2014).
[cited by examiner]
Banerjee; “Intravesical drug delivery: Challenges, current status, opportunities and novel strategies,” 2010, Elsevier; Journal of Controlled Release, vol. 148, pp. 147-159. (Year: 2010).
[cited by examiner]
Frea; “Intravesical gemcitabine for superficial bladder cancer: rationale for a new treatment option,” 2005, BJU international, vol. 96, No. 7, pp. 970-976. (Year: 2005).
[cited by examiner]
Khaled; “Primary chemotherapy with low-dose prolonged infusion gemcitabine and cisplatin in patients with bladder cancer: A Phase II trial,” 2008; Elsevier, Urologic Oncology: Seminars and Investigations, vol. 26, pp. 1…
[cited by examiner]
Laquente; “Antiangiogenic effect of gemcitabine following metronomic administration in a pancreas cancer model,” 2008; American Assn. Cancer, Molecular Cancer Therapeutics, vol. 7, No. 3, pp. 638-647. (Year: 2008).
[cited by examiner]
Shelly; “Intravesical gemcitabine therapy for non-muscle invasive bladder cancer (NMIBC): a systemic review,” 2012; BJU International; Cochrane Review, vol. 109, pp. 496-505. (Year: 2012).
[cited by examiner]
Mattioli et al.; “Intravesical Gemcitabine in Superficial Bladder Cancer: a Phase II Safety, Efficacy and Pharmacokinetic Study,” 2005; International Institute of Anticancer Research; Anticancer Research, vol. 25, pp. 2…
[cited by examiner]
Daneshmand et al.; “The safety, tolerability, and efficacy of a neoadjuvant gemcitabine intravesical drug delivery system (TAR-200) n muscle-invasive bladder cancer patients: a phase I trial,” 2022, Elsevier, Urologic O…
[cited by examiner]
Daneshmand et al.; “Development of TAR-200: A novel targeted releasing system designed to provide sustained delivery of gemcitabine for patients with bladder cancer,” 2025, Elseivier, Urologic Oncology: Seminars and Ori…
[cited by examiner]
Daneshmand et al.; “TAR-200 for Bacillus Calmette-Guerin-Unresponsive High-Risk Non-Muscle-Invasive Bladder Cancer: Results From the Phase Ilb SunRISe-1 Study,” 2025, ASCO; Journal of Clinical Oncology, vol. 43, No. 33,…
[cited by examiner]
AUA Treatment Guidelines https://www.auanet.org/guidelines/bladder-cancer-non-metastatic-muscle-invasive-(2017), pp. 1-62.
[cited by applicant]
Bellmunt et al. (Aug. 2003). “New Drugs and New Approaches in Metastatic Bladder Cancer,” Crit. Rev. Oncol. Hematol. 47(2):195-206.
[cited by applicant]
Cattel et al., “Pharmacokinetic Evaluation of Gemcitabine and 2′,2′-Difluorodeoxycytidine-5′-Triphosphate after Prolonged Infusion in Patients Affected by Different Solid Tumors,” Annals of Oncology, 2006, 17(5): pp. 14…
[cited by applicant]
Cho et al., “The Effects of Intravesical Chemoimmunotherapy with Gemcitabine and Bacillus Calmette-Guerin in Superficial Bladder Cancer: A Preliminary Study,” Journal of Int'l Medicine Research, 2009, 37, pp. 1823-1830.
[cited by applicant]
Cronauer et al., “Inhibitory Effects of the Nucleotide Analogue Gemcitabine on Prostatic Carcinoma Cells,” Prostate, 1996, 28, pp. 172-181.
[cited by applicant]
FDA Grants Fast Track Designation for TAR-200 in Muscle-Invasive Bladder Cancer, The Asco Post, posted Apr. 6, 2018, 1-page.
[cited by applicant]
FDA: Number of fast track designation requests granted, https://www.accessdata.fda.gov/scripts/fdatrack/view/track.cfm?program=cder&status=public&id=CDER-RRDS-Number-of-Fast-Track-Designations . . . , accessed May 1, 20…
[cited by applicant]
Fast Track, Breakthrough Therapy, Accelerated Approval, and Priority Review>Fast Track, https://web.archive.org/web/20190423030711/https://www.fda.gov/ForPatients/Approvals/Fast/ucm405399.htm, accessed May 1, 2019, pp. …
[cited by applicant]
Gontero et al. (2005). “Intravesical Gemcitabine For Superficial Bladder Cancer: Rationale For a New Treatment Option,” BJU International 96: 970-976.
[cited by applicant]
Guhasarkar S. et al. “Intravesical Drug Delivery: Challenges, Current Status, Opportunities, and Novel Strategies,” J. Control Release, 2010, 148(2): pp. 147-159.
[cited by applicant]
Hendricksen et al., “Intravesical Gemcitabine: An Updated of Clinical Results,” Lippincott Williams & Wilkins, Curr. Opin. Urol., 2006, 16: pp. 361-366.
[cited by applicant]
Horinaga et al., “Enhanced Antitumor Effect of Coincident Intravesical Gemcitabine Plus BCG Therapy in an Orthotopic Bladder Cancer Model,” Urology, 2010, 76(5):1267.e1-1267.e6.
[cited by applicant]
Jantscheff et al., “Liposomal Gemcitabine (GemLip)-Efficient Drug Against Hormone-Refractory Dul45 and PC-3 Prostate Cancer Xenografts,” The Prostate, 2009 69: pp. 1151-1163.
[cited by applicant]
Jeon et al., “Induction of Caspase Mediate Apoptosis and Down-Regulation of Nuclear Factory-[kappa]B and Akt Signaling are Involved in the Synergistic Antitumor Effect of Gerncitabine and the Histone Deacetylase Inhibit…
[cited by applicant]
Kamat et al. “Definitions, End Points, and Clinical Trial Designs for Non-Muscle-Invasive Bladder Cancer: Recommendations From the International Bladder Cancer Group,” Journal of Clinical Oncology, 2016, 34(16): pp. 193…
[cited by applicant]
Khaled et al., “Primary chemotherapy with low-dose prolonged infusion gemcitabine and cisplatin in patients with baldder cancer: A Phase II trial,” Urologic Oncology: Seminars and Investigations, 2008, 26:2, pp. 133-136.
[cited by applicant]
Kharkevich, D.A. (2010). Pharmacologia, 10th Edition M., Geotar-Media, p. 73-74, English Translation, 4 pages.
[cited by applicant]
Laquente et al., “Antiangiogenic effect of gemcitabine following metronomic administration in a pancreas cancer model,” Molecular Cancer Therapeutics, 2008, 7(3): pp. 638-647.
[cited by applicant]
Laufer et al., “Intravesical Gemcitabine Therapy for Superficial Transitional Cell Carcinoma of the Bladder: A Phase I and Pharmacokinetic Study,” J. Clin. Oncol., 2003, 21(4): pp. 697.703.
[cited by applicant]
Lein et al., “Low-dose metronomic chemotherapy: A systemic literature analysis,” European Journal of Cancer, 2013, 49: pp. 3387-3395.
[cited by applicant]
Merriam-Webster “Merriam-Webster's Collegiate Dictionary, 11th edition,” 2003; Merriam-Websters Inc; entry for “derivative,” pp. 67, 85, and 768-769. (Year: 2004).
[cited by applicant]
Messing et al., “Effect of Intravesical Instillation of Gemcitabine vs Saline Immediately Following Resection of Suspected Low-Grade Non-Muscle-Invasive Bladder Cancer on Tumor Recurrence,” JAMA, 2018, 319(18): pp. 1880…
[cited by applicant]
Mini et al. “Cellular Pharmacology of Gemcitabine,” Annals of Oncology, 2006, 17(5): v7-v12.
[cited by applicant]
Morant et al., “Response and Palliation in a Phase II Trial of Gemcitabine in Hormone-Refractory Metastatic Prostatic Carcinoma,” Annals of Oncology, 2000, 11: pp. 183-188.
[cited by applicant]
Muenchen et al., “The Study of Gemcitabine in Combination with Other Chemotherapeutic Agents as an Effective Treatment for Prostate Cancer,” Anticancer Research, 2000, 20(2): pp. 735-740.
[cited by applicant]
Nativ et al., “Antineoplastic Effect of Gemcitabine in an Animal Model of Superficial Bladder Cancer,” Urology, 2004, 64(4): pp. 845-848.
[cited by applicant]
PCT International Search Report and Written Opinion for PCT Application No. PCT/US2013/057841 mailed Feb. 14, 2014 (18 pages).
[cited by applicant]
PCT International Search Report and Written Opinion for PCT Application No. PCT/US2015/019262 mailed May 22, 2015 (15 pages).
[cited by applicant]
Reagan-Shaw et al. “A Dose Translation From Animal To Human Studies Revisited,” The FASEB Journal, 2008, 22: pp. 659-661.
[cited by applicant]
Sasaki et al. “Non-Muscle Invasive Bladder Cancer With Multiple Bone Metastasis Without Local Invasion,” Hinyokika Kiyo, 2013, 59(10): pp. 669-672.
[cited by applicant]
Schlack et al. “The Safety and Efficacy of Gemcitabine for The Treatment of Bladder Cancer,” Expert Rev. Anticancer Ther., 2016, 16(3): pp. 255-271.
[cited by applicant]
Shelley et al., “Intravesical Gemcitabine Therapy for Non-Muscle Invasive Bladder Cancer (NMIBC): A Systematic Review,” BJU Int'l, 2012, 109(4): pp. 496-505.
[cited by applicant]
Singapore Search Report of Application No. 11201591482X dated Oct. 28, 2015, pp. 1-3.
[cited by applicant]
Skinner et al. “SWOG S0353: Phase II trial of intravesical gemcitabine in patients with nonmuscle invasive bladder cancer and recurrence after 2 prior courses of intravesical bacillus Calmette-Guerin,” The Journal of Ur…
[cited by applicant]
Sugiyama et al., “Pharmacokinetics of Gemcitabine in Japanese Cancer Patients: The Impact of a Cytidine Deaminase Polymorphism,” Journal of Clinical Oncology, 2007, 25(1): pp. 32-42.
[cited by applicant]
Veltkamp et al., “Oral Administration of Gemcitabine in Patients with Refractory Tumors: A Clinical and Pharmacologic Study,” Clinical Cancer Res., 2008, 14(11): pp. 3447-3486.
[cited by applicant]
Xinwu et al., “Effect of Intravesical Instillatoin Capecitabine Combined with Oxaliplatin on the Recurrence of Bladder Cancer,” Anti-Tumor Pharmacy, 2011, 1(3): pp. 203-205.
[cited by applicant]
Zhulenko, V.N. et al. (2008). Pharmacologia M., KolosS, 34-35, English Translation, 4 pages.
[cited by applicant]
Zlotta, “The management of MCG failure in non-muscle-invasive bladder cancer: an update,” Can Urol Assoc J., 2009, 3(Suppl 4): pp. S199-S205.
[cited by applicant]
Campodonico, et al. “Intravesical Gemcitabine in Recurrent Superficial Bladder Carcinoma: Preliminary Results on Ablative Efficacy and Tolerability,” Anticancer Research, May 2005, vol. 25 pp. 2381-2384 (2005).
[cited by applicant]
Anandadas, C. et al. (Dec. 31, 2013). “Bladder Preservation by Neoadjuvant Chemotherapy Followed by Concurrent Chemoradiotherapy With Gemicitabine in Muscle Invasive Bladder Cancer MIBC,” Clinical Oncology 25: e67-e74, …
[cited by applicant]
Anonymous (2019). Fast Track, Breakthrough Therapy, Accelerated Approval, and Priority Review Fast Track, retrieved from the Internet: https:/web_archive_org/web/20190423030711/https:/www.fda.gov/ForPatients/Approvals/F…
[cited by applicant]
Anonymous (2023). FDA: Number of Fast Track Designation Requests Granted, retrieved from the Internet: https://www.fda.gov/about-fda/center-biologics-evaluation-and-research-cber/fast-track-designation-request-performan…
[cited by applicant]
Anonymous (Apr. 6, 2018). “FDA Grants Fast Track Designation for TAR-200 in Muscle-Invasive Bladder Cancer,” ASCO Post, 3 pages.
[cited by applicant]
Anonymous (Jan. 6, 2017). “TARIS Biomedical Announces Positive Results from Ph1b Trial of TAR-200 (GemRIS™) in Patients with Muscle Invasive Bladder Cancer,” retrieved from the Internet: www.businesswire.com/news/home/2…
[cited by applicant]
Atasoy, B.M. et al. (2014, e-pub. Apr. 25, 2013). “Concurrent Chemoradiotherapy With Low Dose Weekly Gemcitabine In Medically Inoperable Muscle-Invasive Bladder Cancer Patients,” Clin. Transl. Oneal. 16:91-95.
[cited by applicant]
Bellmunt, J. et al. (Aug. 2003). “New Drugs and New Approaches in Metastatic Bladder Cancer,” Crit. Rev. Oncol. Hematol. 47(2):195-206.
[cited by applicant]
Bidnur, S. et al. (Jan. 7, 2016). “Inhibiting Immune Checkpoints for the Treatment of Bladder Cancer,” Bladder Cancer 2(1):15-25.
[cited by applicant]
Borut, K. et al. (2012, e-pub. Sep. 2, 2011). “Phase I Study of Radiochemotherapy With Gemcitabine in Invasive Bladder Cancer,” Radiotherapy and Oncology 102:412-415.
[cited by applicant]
Breyer, B.N. et al. (2010). “Sequential Intravesical Gemcitabine and Mitomycin C Chemotherapy Regimen in Patients With Non-Muscle Invasive Bladder Cancer,” Urol. Oncol. 28(5):510-514, 9 pages.
[cited by applicant]
Caffo, O. et al. (Oct. 22, 2012). “Trimodality Treatment in the Conservative Management of Infiltrating Bladder Cancer: A Critical Review of the Literature,” Critical Reviews in Oncology/Hematology 86(2):176-190.
[cited by applicant]
Cattel, L. et al. (2006). “Pharmacokinetic Evaluation of Gemcitabine and 2′,2′-Difluorodeoxycytidine-5′-Triphosphate after Prolonged Infusion in Patients Affected by Different Solid Tumors,” Annals of Oncology 17(Suppl.…
[cited by applicant]
Chang, S.S. et al. (2017). “Treatment of Non-Metastatic Muscle-Invasive Bladder Cancer: AUA/ASCO/ASTRO/SUO Guidelines,” American Urological Association, 62 pages.
[cited by applicant]
Chauvet, B. et al. (Oct. 31, 1996). “Concurrent Cisplatin and Radiotherapy For Patients With Muscle Invasive Bladder Cancer Who Are Not Candidates For Radical Cystectomy,” The Journal of Urology 156(4):1258-1262. Abstra…
[cited by applicant]
Cho, D.Y. et al. (2009). “The Effects of Intravesical Chemoimmunotherapy with Gemcitabine and Bacillus Calmette-Guerin in Superficial Bladder Cancer: A Preliminary Study,” The Journal of International Medical Research 3…
[cited by applicant]
clinicaltrial.gov NCT03518320 (May 8, 2018). “Safety and Tolerability of TAR-200 and Nivolumab in Subjects with Muscle-Invasive Bladder Cancer,” retrieved from the Internet https://clinicaltrials.gov/ct2/show/NCT0351832…
[cited by applicant]
clinicaltrials.gov. NCT02720367. (Mar. 21, 2016; updated Apr. 19, 2018). “Safety and Tolerability of TAR-200 mg in Subjects With Non-Muscle-Invasive Bladder Cancer,” located at https://clinicaltrials.gov/ct2/history/NCT…
[cited by applicant]
clinicaltrials.gov. NCT02722538. (Apr. 19, 2016). “Safety and Tolerability of GemRIS 225 mg in Subjects With Muscle-Invasive Bladder Cancer,” located at https://clinicaltrials.gov/ct2/history/NCT02722538?V_2=View#StudyP…
[cited by applicant]
clinicaltrials.gov. NCT02722538. (Mar. 30, 2016; last updated Mar. 6, 2018). “Safety and Tolerability of GemRIS 225 mg in Subjects With Muscle-Invasive Bladder Cancer,” located at https://clinicaltrials.gov/ct2/history/…
[cited by applicant]
clinicaltrials.gov. NCT03404791. (Jan. 19, 2018). “Safety and Tolerability of TAR-200 in Subjects With Muscle-Invasive Bladder Cancer Who Are Unfit for Radical Cystectomy,” located at https://www.clinicaltrials.gov/ct2/…
[cited by applicant]
Cockerill, P.A. et al. (Mar. 2016; e-pub May 2, 2015.). “Intravesical Gemcitabine in Combination with Mitomycin C as Salvage Treatment in Recurrent Non-Muscle-Invasive Bladder Cancer,” BJU Int. 117(3):456-462.
[cited by applicant]
Cronauer, M.V. et al. (1996). “Inhibitory Effects of the Nucleotide Analogue Gemcitabine on Prostatic Carcinoma Cells,” The Prostate 18:172-181.
[cited by applicant]
Dalbagni, G. et al. (Jun. 20, 2006). “Phase II Trial of Intravesical Gemcitabine in Bacille Calmette-Guérin-Refractory Transitional Cell Carcinoma of the Bladder,” Journal of Clinical Oncology 24(18):2729-2734.
[cited by applicant]
Dall'Era, M.A. et al. (Jul. 2012). “Contemporary Management of Muscle-Invasive Bladder Cancer,” Expert Rev. Anticancer Ther. 12(7):941-950, 18 pages.
[cited by applicant]
Daneshmand, S. et al. (2017; e-pub. May 30, 2017). “Effect of GemRIS (Gemcitabine-Releasing Intravesical System, TAR-200) on Antitumor Activity in Muscle-Invasive Bladder Cancer (MIBC),” Journal of Clinical Oncology 35(…
[cited by applicant]
Delto, J.C. (2013). “Preclinical Analyses of Intravesical Chemotherapy For Prevention of Bladder Cancer Progression,” Oncotarget 4(2):269-276.
[cited by applicant]
Herr, H.W. et al. (Feb. 2007). “Defining Optimal Therapy for Muscle Invasive Bladder Cancer,” The Journal of Urology 177:437-443.
[cited by applicant]
International Preliminary Report on Patentability, issued Sep. 6, 2016, for PCT Application No. PCT/US2015/019262, filed Mar. 6, 2015, 11 pages.
[cited by applicant]
Kamel, M.H. et al. (Dec. 2011). “Definition of BCG Failure in Non-Muscle Invasive Bladder Cancer in Major Urological Guidelines,” Urotoday Int. J. 4(6):art 82, 4 pages.
[cited by applicant]
Krasnyuk, I.I. et al. (2006). “Pharmaceutical Technology: Technology of Dosage Forms,” Publishing Center Academy, p. 6, 4 pages. English Abstract Translation.
[cited by applicant]
Kroemer, G. et al. (2013, e-pub. Nov. 12, 2012). “Immunogenic Cell Death in Cancer Therapy,” Annu. Rev. Immunol. 31:51-72.
[cited by applicant]
Kumaran, D. et al. (2016, e-pub. Jul. 2, 2016). “Carcinoma of Gall Bladder With Distant Metastasis to Breast Parenchyma. Report of a Case and Review of Literature,” J. Egypt Natl. Canc. Inst. 28(4):263-266.
[cited by applicant]
Leach, D.R. et al. (Mar. 22, 1996). “Enhancement of Antitumor Immunity by CTLA-4 Blockade,” Science 271(5256):1734-1736.
[cited by applicant]
Li, J. et al. (Oct. 2014). Effect of Internal Iliac Artery Chemotherapy after Transurethral Resection of Bladder Tumor For Muscle Invasive Bladder Cancer, Chin J Cancer Res. 26(5):558-563.
[cited by applicant]
Lorenzo, G.D. et al. (Apr. 15, 2010, e-pub. Feb. 16, 2010). “Genncitabine Versus Bacille Calmette-Guerin After Initial Bacille Calmette-Gue'rin Failure in Non-Muscle-Invasive Bladder Cancer,”. Cancer 116:1893-1900.
[cited by applicant]
Ma, J. et al. (Jul. 2016). “Overview of Gemcitabine to Prevent Bladder Cancer Recurrence,” J. Mod. Urol. 21(7):562-566, with English Translation.
[cited by applicant]
Matulewicz, R.S. et la. (2020). “Non-Muscle-Invasive Bladder Cancer: Overview and Contemporary Treatment Landscape of Neoadjuvant Chemoablative Therapies,” Reviews in Urology 22(2):43-51.
[cited by applicant]
Mertens, L.S. et al. (Oct. 2012). “Carboplatin Based Induction Chemotherapy for Nonorgan Confined Bladder Cancer—A Reasonable Alternative for Cisplatin Unfit Patients?” Journal of Urology 188:1108-1114.
[cited by applicant]
Oh, K.S. et al. (Nov. 2, 2009). “Combined-Modality Therapy With Gemcitabine and Radiation Therapy as a Bladder Preservation Strategy: Long-Term Results of a Phase I Trial,” International Journal of Radiation: Oncology B…
[cited by applicant]
Oliveira, M.B. et al. (Apr. 12, 2017). “A Review of Recent Developments on Micro/Nanostructured Pharmaceutical Systems for Intravesical Therapy of the Bladder Cancer,” Pharmaceutical Development and Technology 23(1):1-1…
[cited by applicant]
O'Donnell, P.H. et al. (Mar. 1, 2015). “Prembrolizumab (Pemfro; MK-3475) for Advanced Urothelial Cancer: Results of a Phase IB Study,” Journal of Clinical Oncology 33(7):296, 4 pages.
[cited by applicant]
Pardoll, D.M. (Apr. 2012, e-pub. Mar. 22, 2012). “The Blockade Of Immune Checkpoints In Cancer Immunotherapy,” Nat. Rev. Cancer 12(4): 252-264.
[cited by applicant]
Prasanna, T. et al. (Nov. 2, 2017). “Intravesical Gemcitabine Versus Intravesical Bacillus Calmette-Guerin for the Treatment of Non-Muscle Invasive Bladder Cancer: An Evaluation of Efficacy and Toxicity,” Frontiers in O…
[cited by applicant]
Seront, E. et al. (Jan. 1, 2015). “Molecular Biology and Targeted Therapies for Urothelial Carcinoma,” Cancer Treatment Reviews 41:341-353.
[cited by applicant]
Shariat, S.F. et al. (May 2010). “Update on Intravesical Agents For Non-Muscle-Invasive Bladder Cancer,” Immunotherapy 2(3):381-392, 19 pages.
[cited by applicant]
Stadler, W.M. et al. (Nov. 1997). “Phase II Study of Single-Agent Gemcitabine in Previously Untreated Patients With Metastatic Urothelial Cancer,” J. of Clinical Oncology 15(11):3394-3398.
[cited by applicant]
Sternberg, I.A. et al. (Nov. 2013). “Intravesical Gemcitabine for High Risk, Nonmuscle Invasive Balder Cancer After Bacillus Calmette-Guerin Treatment Failure,” Journal of Urology 190(5):1686-1691.
[cited by applicant]
Sultan, G. et al. (2016). “Neoadjuvant Chemotherapy for Transitional Cell Carcinoma of the Bladder: A Single Centre Experience,” Journal of Life Sciences 10:85-90.
[cited by applicant]
Tsai, Y.-H. et al. (Nov. 2010). “Microemulsions For Intravesical Delivery of Gemcitabine,” Chem. Pharm. Bull. 58(11):1461-1465.
[cited by applicant]
Voena, C. et al. (Feb. 2016). “Advances in Cancer Immunology and Cancer Immunotherapy,” Discovery Medicine 21(114):125-133.
[cited by applicant]
Vogelzang, N.J. et al. (1999). “Gemcitabine and Other New Chemotherapeutic Agents For The Treatment of Metastatic Bladder Cancer,” Urology 53:243-250.
[cited by applicant]
Waddell, J.A. et al. (Dec. 2004). “Intravesical Gemcitabine for Superficial Bladder Carcinoma,” Hospital Pharmacy 39(12):1153-1154.
[cited by applicant]
Wolchok, J.D. et al. (2008). “The Mechanism of Anti-CTLA-4 Activity and the Negative Regulation of T-Cell Activation,” The Oncologist 13(Suppl 4):2-9.
[cited by applicant]
Yuh, B.E. et al. (May 2013). “Pooled Analysis of Clinical Outcomes with Neoadjuvant Cisplatin and Gemcitabine Chemotherapy for Muscle Invasive Bladder Cancer,” Journal of Urology 189:1682-1686.
[cited by applicant]
Food and Drug Administration: Center For Drug Evaluation And Research (CDER). (Jul. 2005). “Guidance for Industry: Estimating the Maximum Safe Starting Dose in Initial Clinical Trials for Therapeutics in Adult Healthy V…
[cited by applicant]
U.S. Appl. No. 18/181,467, filed Mar. 9, 2023 by Giesing et al. (Copy not submitted herewith pursuant to the waiver of 37 C.F.R. § 1.98(a)(2)(iii) issued by the Office on Sep. 21, 2004.).
[cited by applicant]
Addeo, R. et al. (Feb. 1, 2010). “Randomized Phase III Trial on Gemcitabine Versus Mitomycin in Recurrent Superficial Bladder Cancer: Evaluation of Efficacy and Tolerance,” J Clin Oncol. 28(4):543-548.
[cited by applicant]
Balar, A. V. et al. (Feb. 26, 2019). “Keynote 057: Phase II Trial of Pembrolizumab (Pembro) for Patients (pts) with High-risk (HR) Nonmuscle Invasive Bladder Cancer (NMIBC) Unresponsive to Bacillus Calmette-Guerin (BCG)…
[cited by applicant]
Balar, A. V. et al. (Jul. 2021, e-pub. May 26, 2021). “Pembrolizumab Monotherapy for the Treatment of High-risk Non-muscle-invasive Bladder Cancer Unresponsive to BCG (KEYNOTE-057): An Open-label, Single-arm, Multicentr…
[cited by applicant]
Bamias, A. et al. (Jun. 2016). “Outcome of Patients with Nonmetastatic Muscle-Invasive Bladder Cancer Not Undergoing Cystectomy after Treatment with Noncisplatin-Based Chemotherapy and/or Radiotherapy: A Retrospective A…
[cited by applicant]
Dinney, C. P. N. et al. (2013). “Intravesical Valrubicin in Patients with Bladder Carcinoma in Situ and Contraindication to or Failure after Bacillus Calmette-Guérin,” Urol Oncol. 31(8):1635-1642.
[cited by applicant]
Eriksson, E. (2016, e-pub. Sep. 29, 2016). “Gemcitabine Reduces MDSCs, Tregs and TGFBeta-1 While Restoring the Teff/Treg Ratio in Patients with Pancreatic Cancer,” Journal of Translational Medicine 14(282):12 pages.
[cited by applicant]
Fujii, Y. (Mar. 2018, e-pub. Dec. 16, 2017). “Prediction Models for Progression of Non-muscle-invasive Bladder Cancer: A Review,” Int J Urol. 25(3):212-218.
[cited by applicant]
Lee, H. et al. (Jan. 20, 2011). “An Intravesical Device for The Sustained Delivery of Lidocaine to the Bladder,” J Control Release 149(2):133-139.
[cited by applicant]
Mirza, A. et al. (2016, e-pub. Apr. 27, 2016). “Bladder Preservation for Muscle Invasive Bladder Cancer,” BI Cancer 2(2):151-163.
[cited by applicant]
Necchi, A. et al. (May 3, 2024). “P2-01 TAR-200 in Patients with Bacillus Calmette-Guérin-Unresponsive High-risk Non-muscle-invasive Bladder Cancer: Results from Sunrise-1 Study,” Journal of Urology 211(5S2):E1.
[cited by applicant]
Sylvester, R. J. et al. (2016). “Systematic Review and Individual Patient Data Meta-Analysis of Randomized Trials Comparing a Single Immediate Instillation of Chemotherapy After Transurethral Resection with Transurethra…
[cited by applicant]
Tan, W. S. et al. (2018, e-pub. Sep. 25, 2018). “Intravesical Device-assisted Therapies for Non-muscle-invasive Bladder Cancer,” Nat Rev Urol 15(11):667-685, 18 pages.
[cited by applicant]
Woldu, S. et al. (Mar. 2017). “Guideline of Guidelines—Non-Muscle Invasive Bladder Cancer,” BJU Int. 119(3):371-380.
[cited by applicant]
Zhao, P. et al. (Jan. 2017, e-pub. Nov. 17, 2016). “Gemcitabine Treatment Enhanced the Anti-Tumor Effect of Cytokine Induced Killer Cells by Depletion of CD4+CD25bri Regulatory T Cells,” Immunology Letters 181:36-44.
[cited by applicant]