IP Library › Granted Patent US 12,691,110
Granted Patent B2
US 12,691,110 · App. 18/193,270 · Granted Jul 28, 2026

Topotecan for proliferative vitreoretinopathy

Inventors: Leo A. Kim (Brookline, MA); Joseph F. Arboleda-Velasquez (Newton, MA); Dean Eliott (Boston, MA); Elizabeth Jeffries Rossin (Charlestown, MA)
Assignee: Massachusetts Eye and Ear Infirmary
A61K31/475A61K9/0019A61K9/0048A61K45/06A61P27/02
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 12,691,110
App. No.
18/193,270
Granted
Jul 28, 2026
Kind
B2
Abstract

The use of topotecan, e.g., repeated dosing or sustained-release formulations of topotecan, for treating or reducing risk of proliferative vitreoretinopathy (PVR) or epiretinal membranes (ERM), e.g., after surgical vitrectomy to treat retinal detachment, is described herein.

Claims (23)

1 . A method of treating proliferative vitreoretinopathy (PVR) in a subject, the method comprising administering to the subject multiple intravitreal injections of topotecan over a period of at least one, two, three, four, or more months, given no more frequently than weekly.

2 . The method of claim 1 , comprising administering five or more intravitreal injections of topotecan.

3 . The method of claim 2 , comprising administering seven intravitreal injections of topotecan.

4 . The method of claim 1 , wherein each injection provides a dose of about 5 mcg, about 6 mcg, about 7 mcg, about 8 mcg, about 9 mcg, or about 10 mcg topotecan, preferably administered in a volume of 0.1 ml.

5 . The method of claim 4 , wherein each injection provides a dose of about 8 mcg topotecan, preferably administered in a volume of 0.1 ml.

6 . The method of claim 1 , wherein the subject is undergoing an ocular surgical procedure that increases the subject's risk of developing PVR.

7 . The method of claim 6 , wherein the ocular surgical procedure is a pars plana vitrectomy (PPV), Retinal Detachment (RD) surgery; ERM surgery; scleral buckle surgery; or a procedure in the other eye.

8 . The method of claim 6 , wherein the subject requires a PPV to treat a rhegmatagenous retinal detachment (RRD) secondary to trauma; preexisting proliferative vitreoretinopathy; or for other indications associated with high risk condition for PVR development.

9 . The method of claim 8 , wherein the indication associated with high risk condition for PVR development is a giant retinal tear, a retinal break larger than 3 disc areas, a long-standing retinal detachment, or a detachment associated with hemorrhage.

10 . The method of claim 6 , wherein the topotecan is administered preoperatively, intraoperatively during surgery, and/or postoperatively.

11 . The method of claim 10 , wherein:

a first injection is given preoperatively within one week from surgery;

a second injection is given intraoperatively during surgery; and

five or more injections are given postoperatively, preferably at 2 weeks, 4 weeks, 8 weeks, 12 weeks and 16 weeks postoperatively.

12 . The method of claim 11 , comprising administering additional injections after the seventh injection.

13 . The method of claim 1 , wherein the topotecan is administered in combination with one or more additional therapeutic agents.

14 . The method of claim 13 , wherein the one or more additional therapeutic agents is selected from the group consisting of melphalan, daunorubicin, lenalidomide, daclatsvir, stavudine, resveratrol, marbofloxacin, bendamustine HCl, semagacestat, methotrexate, and a Runx1 inhibitor, or an analogue thereof.

15 . The method of claim 14 , wherein the one or more additional therapeutic agents is administered simultaneously with the topotecan.

16 . The method of claim 1 , wherein the topotecan is administered posterior to the limbus.

17 . A method of treating proliferative vitreoretinopathy (PVR) in a subject, the method comprising intravitreally administering to the subject a sustained release formulation of topotecan over at least a four-month period.

18 . The method of claim 17 , wherein the sustained release formulation is or comprises a lipid-encapsulated formulation; multivesicular liposome (MVL) formulations of topotecan; nano- or microparticles; polyion complex (PIC) micelles; or bioadhesive polymers.

19 . The method of claim 18 , wherein the bioadhesive polymers comprise one or more of hydroxypropyl methylcellulose (HPMC), carboxymethylcellulose (CMC), polyacrylic acid (PAA), or hyaluronic acid (HA).

20 . A method of treating proliferative vitreoretinopathy (PVR) in a subject, the method comprising implanting into the eye of the subject a device that provides sustained release of topotecan, and optionally one or more additional therapeutic agents, over at least a four-month period, preferably wherein the device is implanted within a week before the subject undergoes an ocular surgical procedure that increases the subject's risk of developing PVR.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 23, 2026
From: THE SCHEPENS EYE RESEARCH INSTITUTE, INC.
To: MASSACHUSETTS EYE AND EAR INFIRMARY
Reel/Frame 075058/0587 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 12, 2024
From: KIM, LEO A.; ARBOLEDA-VELASQUEZ, JOSEPH F.; ELIOTT, DEAN; ROSSIN, ELIZABETH JEFFRIES
To: THE SCHEPENS EYE RESEARCH INSTITUTE, INC.
Reel/Frame 066738/0430 →
Continuity (2)
Provisional Application 63325459 · Mar 30, 2022
Related Publication 20230355611A1 · Nov 9, 2023
References Cited (38)
US 3405122A · Berger et al. · 1968 [cited by applicant]
US 5036101A · Hsu et al. · 1991 [cited by applicant]
US 5041438A · Hsu · 1991 [cited by applicant]
US 5141735A · Bellemin et al. · 1992 [cited by applicant]
US 5164376A · Hsu et al. · 1992 [cited by applicant]
US 5641773A · Pardee et al. · 1997 [cited by applicant]
US 9173775B2 · Haffner et al. · 2015 [cited by applicant]
US 9668915B2 · Haffner et al. · 2017 [cited by applicant]
US 10285853B2 · Rangel-Friedman et al. · 2019 [cited by applicant]
US 20060035955A1 · Zeldis · 2006 [cited by applicant]
US 20140004082A1 · Liu et al. · 2014 [cited by applicant]
US 20170128424A1 · Rothstein · 2017 [cited by examiner]
US 20180369017A1 · Schieber et al. · 2018 [cited by applicant]
US 20200377888A1 · Kim et al. · 2020 [cited by applicant]
US 20210030590A1 · Blanda et al. · 2021 [cited by applicant]
WO WO2022229932A1 · 2022 [cited by examiner]
Miwa et al. (Pharmacological HIF inhibition prevents retinal neovascularization with improved visual function in a murine oxygen-induced retinopathy mode), Neurochemistry International 128 (2019) 21-31. [cited by examiner]
Amarnani et al., “Abstract: Identification of Drug Candidates using a Patient-Derived Model of Proliferative Vitreoretinopathy,” Abstract, Presented at Proceedings of the 2021 ARVO Annual Meeting, Virtual, Jun. 2021; 62… [cited by applicant]
Amarnani et al., “Poster: Identification of Drug Candidates using a Patient-Derived Model of Proliferative Vitreoretinopathy,” Poster, Presented at Proceedings of the 2021 ARVO Annual Meeting, Virtual, Jun. 2021, 1 page. [cited by applicant]
Asato et al., “Comparison of gene expression profile of epiretinal membranes obtained from eyes with proliferative vitreoretinopathy to that of secondary epiretinal membranes,” PLoS One, 2013, 8(1):e54191, 8 pages. [cited by applicant]
Cunningham et al., “Identification of benzodiazepine Ro5-3335 as an inhibitor of CBF leukemia through quantitative high throughput screen against RUNX1-CBFβ interaction,” Proc Natl Acad Sci USA, Sep. 2012, 109(36):14592… [cited by applicant]
Haghjou et al., “Sustained release intraocular drug delivery devices for treatment of uveitis,” J Ophthalmic Vis Res., Oct. 2011, 6(4):317-329. [cited by applicant]
Haubrich et al., “A randomized trial of the activity and safety of Ro 24-7429 (Tat antagonist) versus nucleoside for human immunodeficiency virus infection. The AIDS Clinical Trials Group 213 Team,” J Infect Dis, Nov. 1… [cited by applicant]
Hiscott et al., “Pathobiology of epiretinal and subretinal membranes: possible roles for the matricellular proteins thrombospondin 1 and osteonectin (SPARC),” Eye, Jul. 2002, 16(4):393-403. [cited by applicant]
Hiscott et al., “Retinal pigment epithelial cells in epiretinal membranes: an immunohistochemical study,” Br J Ophthalmol., Oct. 1984, 68(10):708-15. [cited by applicant]
Kim et al., “Controlled drug release from an ocular implant: an evaluation using dynamic three-dimensional magnetic resonance imaging,” Invest. Ophthalmol. Vis. Sci., Aug. 2004, 45(8):2722-2731. [cited by applicant]
Lean et al., “Classification of proliferative vitreoretinopathy used in the silicone study. The Silicone study group,” Ophthalmology, Jun. 1989, 96(6):765-771. [cited by applicant]
Lee et al., “Biodegradable implants for sustained drug release in the eye,” Pharm Res., Oct. 2010, 27(10):2043-53. [cited by applicant]
Machemer et al., “An updated classification of retinal detachment with proliferative vitreoretinopathy,” Am J Ophthalmol, Aug. 1991, 112(2):159-65. [cited by applicant]
Palakurthi et al., “Investigation of kinetics of methotrexate for therapeutic treatment of intraocular lymphoma,” Current Eye Research, Oct. 2010, 35(12):1105-1115. [cited by applicant]
Patankar et al., “Topophore C: a liposomal nanoparticle formulation of topotecan for treatment of ovarian cancer,” Invest New Drugs, Feb. 2013, 31(1):46-58. [cited by applicant]
Souza et al., “Development of topotecan loaded lipid nanoparticles for chemical stabilization and prolonged release,” Eur J Pharm Biopharm, Sep. 2011, 79(1):189-96. [cited by applicant]
Taich et al., “Sustained-release hydrogels of topotecan for retinoblastoma,” Colloids Surf B Biointerfaces, Oct. 2016, 146:624-31. [cited by applicant]
The Retina Society Terminology Committee, “The classification of retinal detachment with proliferative vitreoretinopathy,” Ophthalmology, Feb. 1983, 90(2):121-5. [cited by applicant]
Velez and Whitcup, “New developments in sustained release drug delivery for the treatment of intraocular disease,” Br J Ophthalmol, 1999, 83:1225-1229. [cited by applicant]
Falavarjani et al., “Intrasilicone oil injection of bevacizumab at the end of retinal reattachment surgery for severe proliferative vitreoretinopathy,” Eye, Feb. 2014, 28(5):576-580. [cited by applicant]
Grierson et al., “Non-vascular vitreoretinopathy: the cells and the cellular basis of contraction,” Eye, Nov. 1996, 10(6):671-684. [cited by applicant]
Jusufbegovic et al., “Risk factors and prevention of proliferative vitreoretinopathy,” Expert Review of Ophthalmology, Sep. 2015, 10(5):431-440. [cited by applicant]