IP Library › Granted Patent US 12,440,568
Granted Patent B2
US 12,440,568 · App. 19/066,754 · Granted Oct 14, 2025

Material and method for treating internal cavities

Inventors: Asher Holzer (Raanana, IL); Dorit Daniel (Raanana, IL); Michael Mullerad (Tel Aviv, IL); Jaime De La Zerda (Haifa, IL); Uri Shpolansky (Pardes Hana, IL); Nadav Malchi (Pardes Hanna-Karkur, IL); Yosh Dollberg (Raanana, IL); Dor Tal (Hadera, IL); Yossi Yavin (Mikhmoret, IL)
Assignee: UroGen Pharma Ltd.
A61K47/34A61K9/0034A61K9/06A61K31/07A61K31/122A61K31/167A61K31/192A61K31/337A61K31/397A61K31/407A61K31/59A61K31/704A61K31/7068A61K38/4893A61K47/10A61K47/38
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 12,440,568
App. No.
19/066,754
Granted
Oct 14, 2025
Kind
B2
Abstract

A hydrophilic biocompatible sustained-release material is disclosed. The material comprises amounts of an ethylene oxide/propylene oxide block copolymer, HPMC, and water, effective to produce a composition of sufficiently low viscosity at room temperature to be injectable into an internal body cavity via a tube inserted within a urinary catheter. At body temperature, the material exhibits a much higher viscosity and will stably adhere to the internal surface of a body cavity. As the material dissolves, a therapeutic agent incorporated therein is slowly released to the body cavity, while the material itself is excreted from the body.

Claims (17)

1. A method of treating superficial bladder cancer comprising:

(a) preparing a composition by incorporating an effective amount of mitomycin C and an accompanying excipient into a thermoreversible hydrogel, the accompanying excipient being mannitol; and

(b) administering the composition to the urinary bladder of a human in need of such treatment,

wherein the thermoreversible hydrogel comprises:

(i) 23% to 27% (w/w) poloxamer 407;

(ii) 0.15% to 0.2% (w/w) hydroxypropylmethylcellulose;

(iii) 0.5% to 1.8% (w/w) PEG-400; and

(iv) water.

2. The method of claim 1 , wherein the composition is administered via a urinary catheter.

3. The method of claim 1 , wherein the thermoreversible hydrogel comprises 27% (w/w) poloxamer 407.

4. The method of claim 3 , wherein the composition is administered via a urinary catheter.

5. The method of claim 1 , wherein the thermoreversible hydrogel comprises 0.5% to 1.0% (w/w) PEG-400.

6. The method of claim 5 , wherein the composition is administered via a urinary catheter.

7. The method of claim 5 , wherein the thermoreversible hydrogel comprises 27% (w/w) poloxamer 407.

8. The method of claim 7 , wherein the composition is administered via a urinary catheter.

9. The method of claim 7 , wherein the thermoreversible hydrogel comprises 1.0% (w/w) PEG-400.

10. The method of claim 9 , wherein the composition is administered via a urinary catheter.

Assignments (2)
SECOND AMENDED AND RESTATED PATENT SECURITY AGREEMENT Recorded Mar 2, 2026
From: UROGEN PHARMA LTD.
To: BIOPHARMA CREDIT PLC, AS COLLATERAL AGENT
Reel/Frame 074994/0338 →
AMENDED AND RESTATED PATENT SECURITY AGREEMENT Recorded Aug 18, 2025
From: UROGEN PHARMA LTD.
To: BIOPHARMA CREDIT PLC, AS COLLATERAL AGENT
Reel/Frame 072472/0233 →
Continuity (9)
Continuation 18625862 · Apr 3, 2024
Continuation 18129497 · Mar 31, 2023
Division 17566882 · Dec 31, 2021
Continuation 16518511 · Jul 22, 2019
Continuation 14054731 · Oct 15, 2013
Continuation In Part 13553198 · Jul 19, 2012
Continuation In Part PCTIL2011000069 · Jan 20, 2011
Provisional Application 61296589 · Jan 20, 2010
Related Publication 20250195665A1 · Jun 19, 2025
References Cited (63)
US 6286513B1 · Au et al. · 2001 [cited by applicant]
US 6482435B1 · Stratton et al. · 2002 [cited by applicant]
US 8361490B2 · Holzer et al. · 2013 [cited by applicant]
US 9040074B2 · Holzer et al. · 2015 [cited by applicant]
US 9801854B1 · Strauss-Ayali et al. · 2017 [cited by applicant]
US 9950069B2 · Holzer · 2018 [cited by examiner]
US 10039832B2 · Holzer et al. · 2018 [cited by applicant]
US 10471150B2 · Konorty et al. · 2019 [cited by applicant]
US 20040009212A1 · Tsai · 2004 [cited by applicant]
US 20070275110A1 · Dott et al. · 2007 [cited by applicant]
US 20090142259A1 · Gao et al. · 2009 [cited by applicant]
US 20090214685A1 · Hunt · 2009 [cited by applicant]
US 20100015200A1 · McClain et al. · 2010 [cited by applicant]
US 20130046275A1 · Holzer et al. · 2013 [cited by applicant]
US 20140105884A1 · Konorty et al. · 2014 [cited by applicant]
US 20140142191A1 · De La Zerda et al. · 2014 [cited by applicant]
US 20150366974A1 · Holzer et al. · 2015 [cited by applicant]
US 20160256391A1 · Schuldt-Lieb et al. · 2016 [cited by applicant]
US 20170112935A1 · Holzer et al. · 2017 [cited by applicant]
US 20170128424A1 · Rothstein · 2017 [cited by applicant]
US 20170136127A1 · Maki et al. · 2017 [cited by applicant]
US 20170143833A1 · De La Zerda et al. · 2017 [cited by applicant]
US 20200114008A1 · Konorty · 2020 [cited by applicant]
US 20220118096A1 · Konorty · 2022 [cited by applicant]
US 20220202773A1 · Hionidi et al. · 2022 [cited by applicant]
US 20230233685A1 · Holzer et al. · 2023 [cited by applicant]
US 20230241220A1 · Holzer et al. · 2023 [cited by applicant]
US 20230241221A1 · Holzer et al. · 2023 [cited by applicant]
EP 0386960A2 · 1990 [cited by applicant]
WO 2011089604A2 · 2011 [cited by applicant]
WO 2013011504A1 · 2013 [cited by applicant]
WO 2018169960A1 · 2018 [cited by applicant]
WO 2022123480A1 · 2022 [cited by applicant]
L. Zhang, et al., “Development and in-vitro evaluation of sustained release Poloxamer 407 (P407) gel formulations of ceftiofur”, J. Controlled Release 85 (2002) 73-81. [cited by applicant]
E.J. Ricci, et al., “Sustained release of lidocaine from Poloxamer 407 gels”, Int'l J. Pharmaceutics 288 (2005) 235-244. [cited by applicant]
S.D. Desai, et al., “In Vitro Evaluation of Pluronic F127-Based Controlled-Release Ocular Delivery Systems for Pilocarpine”, J. Pharmaceutical Sciences, vol. 87, No. 2, pp. 226-230 (1998). [cited by applicant]
S.M. Abdel-Hamid, et al., “Formulation of an antispasmodic drug as a topical local anesthetic”, Int'l J. Pharmaceutics 326 (2006) 107-118. [cited by applicant]
H.T. Ta, et al., “Injectable chitosan hydrogels for localised cancer therapy”, Journal of Controlled Release, vol. 126, pp. 205-216 (2008). [cited by applicant]
C.P. Calderon, et al., “Deep Convolutional Neural Network Analysis of Flow Imaging Microscopy Data to Classify Subvisible Particles in Protein Formulations”, Journal of Pharmaceutical Sciences, vol. 107, pp. 999-1008 (2… [cited by applicant]
Y. You, et al., “Intraoperative Mitomycin C in Dacryocystorhinostomy”, Opthalmic Plastic and Reconstructive Surgery, vol. 17, No. 2, pp. 115-119 (2001). [cited by applicant]
H. Wang, U.S. Pharmacopeia, http://www.pharmacopeia.cn/v29240/usp29nf24s0_m66210.html, vol. 29, No. 6, p. 2020 (2007), retrieved from the internet on Feb. 21, 2024. [cited by applicant]
X. Gao, et al., “Bladder Tissue Uptake of Mitomycin C during Intravesical Therapy Is Linear with Drug Concentration in Urine”, Clinical Cancer Research, vol. 3, pp. 139-143 (1998). [cited by applicant]
T.D. Schmittgen, et al., “Pharmacodynamics of Mitomycin C in Cultured Human Bladder Tumors”, Cancer Research, vol. 51, pp. 3849-3856 (1991). [cited by applicant]
Technical Bulletin, Pluronic Block Copolymer NF Grades (Poloxamer NF Grades), BASF The Chemical Company, 2 pages (2002). [cited by applicant]
S. Miyazaki, et al., “Antitumor Effect of Pluronic F-127 Gel Containing Mitomycin C on Sarcoma-180 Ascites Tumor in Mice”, Chem. Pharm. Bull. 40(8) 2224-2226 (1992). [cited by applicant]
E. Bilensoy, et al., “Mucoadhesive, Thermosensitive, Prolonged-Release Vaginal Gel for Clotrimazole: beta-Cyclodextrin Complex”, AAPS PharmSciTech 2006; 7(2) Article 38 (http://www.aapspharmscitech.org). [cited by applicant]
Jelmyto (mitomycin) [package insert]. Princeton, NJ: UroGen Pharma, Inc; Apr. 2020. [cited by applicant]
International Search Report dated Jan. 18, 2012, in corresponding PCT/IL2011/000069 (7 pages). [cited by applicant]
Written Opinion dated Jan. 18, 2012, in corresponding PCT/IL2011/000069 (12 pages). [cited by applicant]
R.A. Leder, et al., “Transitional Cell Carcinoma of the Pelvicalices and Ureter”, AJR 155:713-722 (1990). [cited by applicant]
R.A. Badalament, et al., “Treatment of Superficial Bladder Cancer With Intravesical Chemotherapy”, Seminars in Surgical Oncology 1997; 13: 335-341. [cited by applicant]
E. Bilensoy, et al., “Thermosensitive vaginal gel formulation for the controlled release of clotrimazole via complexation to beta-cyclodextrin”, Journal of Controlled Release, Nov. 28, 2006; 116(2):e107-9. [cited by applicant]
E. DeBruijn, et al., “Pharmacodynamics and Pharmacokinetics of Intravesical Mitomycin C Upon Different Dwelling Times”, Int. J. Cancer: 51, 359-364 (1992). [cited by applicant]
G. Dumortier, et al., “A Review of Poloxamer 407 Pharmaceutical and Pharmacological Characteristics”, Pharmaceutical Research, vol. 23, No. 12, pp. 2709-2728 (2006). [cited by applicant]
J.J. Escobar-Chavez, et al., “Applications of Thermoreversible Pluronic F-127 Gels in Pharmaceutical Formulations”, J. Pharm. Pharmaceut. Sci. 9 (3): 339-358, 2006. [cited by applicant]
A. Hatefi, et al., “Biodegradable injectable in situ forming drug delivery systems”, Journal of Controlled Release 80 (2002) 9-28. [cited by applicant]
R. Ivanova, et al., “Effect of Pharmaceutically Acceptable Glycols on the Stability of the Liquid Crystalline Gels Formed by Poloxamer 407 in Water”, Journal of Colloid and Interface Science 252, 226-235 (2002). [cited by applicant]
K.S. Rathore, “In-Situ Gelling Ophthalmic Drug Delivery System: An Overview”, International Journal of Pharmacy and Pharmaceutical Sciences, vol. 2, suppl. 4, pp. 30-34 (2010). [cited by applicant]
T.D. Schmittgen, et al., “Correlation of Human Bladder Tumor Histoculture Proliferation and Sensitivity to Mitomycin C with Tumor Pathobiology”, The Journal of Urology, vol. 152, 1632-1636 (1994). [cited by applicant]
V. Serretta, “Optimizing intravesical chemotherapy in patient with non muscle invasive bladder carcinoma”, Archivio Italiano di Urologia e Androlgia 2008; 80, 4, pp. 143-148. [cited by applicant]
D. Perez-Montiel, et al., “High-grade urothelial carcinoma of the renal pelvis: clinicopathologic study of 108 cases with emphasis on unusual morphologic variants”, Modern Pathology (2006) 19, 494-503. [cited by applicant]
J. A. Eastham, et al., “Technique of Mitomycin C Instillation in the Treatment of Upper Urinary Tract Urothelial Tumors”, The Journal of Urology, vol. 150, 324-325 (1993). [cited by applicant]
J. H. Beijnen, et al., “Mitomycin C”, Analytical Profiles of Drug Substances, Academic Press, vol. 16, pp. 361-401 (1987). [cited by applicant]