Granted Patent
B2
US 12,551,368 · App. 17/671,060 · Granted Feb 17, 2026
Bioerodible ocular drug delivery insert and therapeutic method
Inventors:
Said Saim (Watertown, MA); Michelle Howard-Sparks (Watertown, MA); Dario Paggiarino (Watertown, MA); Basel Karzoun (Watertown, MA); Jianbing Chen (Watertown, MA)
Assignee:
EyePoint Pharmaceuticals, Inc.
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Abstract
This invention relates to implantable bioerodible inserts for delivering an active pharmaceutical ingredient to the eye. The invention also relates to methods of treatment using such inserts as well as methods of manufacturing such inserts.
Claims (14)
1 . An ocular drug delivery insert consisting of a solid matrix core comprising a matrix polymer and vorolanib or a pharmaceutically acceptable salt thereof, wherein the amount of the vorolanib or pharmaceutically acceptable salt thereof in the insert is about 75% w/w to about 98% w/w, wherein the matrix polymer is polyvinyl alcohol, wherein the drug release rate for the insert is about 0.1 μg/day to about 20 μg/day and is substantially constant for at least about 14 days, and wherein the duration of drug release is at least about 12 weeks.
2 . The ocular drug delivery insert of claim 1 , wherein the amount of the vorolanib or pharmaceutically acceptable salt thereof in the insert is about 800 μg to about 2000 μg.
3 . The ocular drug delivery insert of claim 1 , wherein the insert is sized and shaped to fit through a cannula or needle of 20 gauge or smaller.
4 . The ocular drug delivery insert of claim 3 , wherein the insert is rod shaped and has a length of about 6 mm to 10 mm.
5 . The ocular drug delivery insert of claim 1 , wherein the amount of matrix polymer in the core is about 4% w/w to about 25% w/w.
6 . The ocular drug delivery insert of claim 1 , wherein the amount of matrix polymer in the core is about 1% w/w to about 10% w/w.
7 . The ocular drug delivery insert of claim 1 , wherein the duration of drug release is at least about 18 weeks.
8 . An ocular drug delivery insert consisting of (a) a solid matrix core comprising polyvinyl alcohol and vorolanib or a pharmaceutically acceptable salt thereof, and (b) a coating comprising polyvinyl alcohol substantially surrounding the core, wherein the amount of the vorolanib or pharmaceutically acceptable salt thereof in the insert is about 75% w/w to about 98% w/w, wherein the drug release rate for the insert is about 0.1 μg/day to about 20 μg/day, and wherein the duration of drug release is at least about 12 weeks.
9 . The ocular drug delivery insert of claim 8 , wherein the amount of the vorolanib or pharmaceutically acceptable salt thereof in the insert is about 800 μg to about 2000 μg.
10 . The ocular drug delivery insert of claim 8 , wherein the insert is sized and shaped to fit through a cannula or needle of 20 gauge or smaller.
11 . The ocular drug delivery insert of claim 8 , wherein the insert is rod shaped and has a length of about 6 mm to 10 mm.
12 . The ocular drug delivery insert of claim 8 , wherein the amount of matrix polymer in the core is about 4% w/w to about 25% w/w.
13 . The ocular drug delivery insert of claim 8 , wherein the amount of matrix polymer in the core is about 1% w/w to about 10% w/w.
14 . The ocular drug delivery insert of claim 8 , wherein the duration of drug release is at least about 18 weeks.
Assignments (7)
CHANGE OF NAME
Recorded Jul 1, 2026
From: EYEPOINT PHARMACEUTICALS, INC.
To: EYEPOINT, INC.
Reel/Frame 075945/0459 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Aug 28, 2025
From: CHEN, JIANBING
To: CONTROL DELIVERY SYSTEMS, INC.
Reel/Frame 072675/0223 →
MERGER AND CHANGE OF NAME
Recorded Aug 28, 2025
From: PSIVIDA INC.; CONTROL DELIVERY SYSTEMS, INC.
To: PSIVIDA INC.
Reel/Frame 072675/0235 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Aug 28, 2025
From: EYEPOINT PHARMACEUTICALS US, INC.
To: EYEPOINT PHARMACEUTICAL, INC.
Reel/Frame 072675/0256 →
CHANGE OF NAME
Recorded Aug 28, 2025
From: PSIVIDA US, INC.
To: EYEPOINT PHARMACEUTICALS US, INC.
Reel/Frame 073067/0650 →
CHANGE OF NAME
Recorded Aug 28, 2025
From: PSIVIDA INC.
To: PSIVIDA US, INC.
Reel/Frame 072675/0250 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Sep 21, 2022
From: SAIM, SAID; HOWARD-SPARKS, MICHELLE; PAGGIARINO, DARIO; KARZOUN, BASEL
To: EYEPOINT PHARMACEUTICALS, INC.
Reel/Frame 061165/0912 →
Continuity (5)
Continuation In Part
PCTUS2021050085
· Sep 13, 2021
Provisional Application
63190052
· May 18, 2021
Provisional Application
63176430
· Apr 19, 2021
Provisional Application
63078265
· Sep 14, 2020
References Cited (79)
US 6713081B2
· Robinson
· 2004
[cited by examiner]
US 6891044B2
· Kania et al.
· 2005
[cited by applicant]
US 7622593B2
· Gray et al.
· 2009
[cited by applicant]
US 7683057B2
· Liang et al.
· 2010
[cited by applicant]
US 8039470B2
· Liang et al.
· 2011
[cited by applicant]
US 8524709B2
· Liang et al.
· 2013
[cited by applicant]
US 8791140B2
· Campeta et al.
· 2014
[cited by applicant]
US 8871241B2
· Chou et al.
· 2014
[cited by applicant]
US 20080063687A1
· Chou et al.
· 2008
[cited by applicant]
US 20160317438A1
· Ashton
· 2016
[cited by applicant]
US 20180296525A1
· Roizman et al.
· 2018
[cited by applicant]
CN 110730655A
· 2020
[cited by applicant]
WO 2004066980A2
· 2004
[cited by applicant]
WO 2011079232A1
· 2011
[cited by applicant]
WO 2018059556A1
· 2018
[cited by applicant]
WO 2019202603A1
· 2019
[cited by applicant]
WO WO2020177678A1
· 2020
[cited by examiner]
Khanani et al., “Sustained-release Tyrosine Kinase Inhibitors for the Treatment of nAMD,” Retinal Physician 19:23-25, 30-32 (2022).
[cited by applicant]
Bendell et al., “Phase I, First-in-Human, Dose-Escalation Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Vorolanib in Patients with Advanced Solid Tumors,” Oncologist, 24(4):455-e121 (2019).
[cited by applicant]
Byron et al., “Effects of heat treatment on the permeability of polyvinyl alcohol films to a hydrophilic solute,” Journal of Pharmaceutical Sciences, 76(1):65-67 (1987).
[cited by applicant]
Clinical Trials Identifier: NCT01674569, “Pilot Study of X-82 in Patients With Wet AMD,” Actual Study Completion Date: Feb. 2015; Tyrogenex.
[cited by applicant]
Clinical Trials Identifier: NCT02348359, “X-82 to Treat Age-related Macular Degeneration,” Actual Study Completion Date: Jan. 12, 2018; Tyrogenex.
[cited by applicant]
Clinical Trials Identifier: NCT02452385, “Phase 1 Study of CM082 in Patients With wAMD,” Estimated Study Completion Date: Jun. 2020; AnewPharma.
[cited by applicant]
Clinical Trials Identifier: NCT03710863, “Safety and Tolerability of Oral CM082 in Patients With wAMD,” Estimated Study Completion Date: Jan. 1, 2022; AnewPharma.
[cited by applicant]
Cohen et al., “APEX: a phase II randomised clinical trial evaluating the safety and preliminary efficacy of oral X-82 to treat exudative age-related macular degeneration,” British Journal of Ophthalmology, 105(5):716-72…
[cited by applicant]
Duker J., “8-month Results of a Tyrosine Kinase Inhibitor (Vorolanib) in a Bio-erodible Durasert Implant for Previously Treated Wet AMD: The DAVIO Trial,” U.S. Securities and Exchange Commission, Feb. 2022 <https://www.…
[cited by applicant]
“EyePoint, Equinox enter licensing agreement for vorolanib,” Ocular Surgery News, Feb. 4, 2020 <https://www.healio.com/news/ophthalmology/20200204/eyepoint-equinox-enter-licensing-agreement-for-vorolanib>.
[cited by applicant]
EyePoint Pharmaceuticals, Inc. “Investor Presentation,” U.S. Securities and Exchange Commission, Feb. 2020, Exhibit 99.1 <https://www.sec.gov/Archives/edgar/data/0001314102/000156459020005550/eypt-ex991_6.htm>.
[cited by applicant]
EyePoint Pharmaceuticals, Inc. “Cantor Virtual Healthcare Conference,” U.S. Securities and Exchange Commission, Sep. 15, 2020, Exhibit 99.1 <https://www.sec.gov/Archives/edgar/data/0001314102/000156459020043596/eypt-ex9…
[cited by applicant]
EyePoint Pharmaceuticals, Inc. “Investor Presentation: Delivering Innovation to the Eye,” U.S. Securities and Exchange Commission, Jun. 2021, Exhibit 99.1 <https://www.sec.gov/Archives/edgar/data/0001314102/000156459021…
[cited by applicant]
EyePoint Pharmaceuticals, Inc. “Investor Presentation: Delivering Innovation to the Eye,” U.S. Securities and Exchange Commission, Aug. 2021, Exhibit 99.1 <https://www.sec.gov/Archives/edgar/data/0001314102/000156459021…
[cited by applicant]
EyePoint Pharmaceuticals, Inc. “EYP-1901 Davio Study Interim Results: Delivering Innovation to the Eye,” U.S. Securities and Exchange Commission, Nov. 13, 2021, Exhibit 99.2 <https://www.sec.gov/Archives/edgar/data/0001…
[cited by applicant]
EyePoint Pharmaceuticals, Inc. “Investor Presentation: Delivering Innovation to the Eye,” U.S. Securities and Exchange Commission, Jan. 2022, Exhibit 99.1 <https://www.sec.gov/Archives/edgar/data/0001314102/000156459022…
[cited by applicant]
EyePoint Pharmaceuticals, Inc. “Investor Presentation: Delivering Innovation to the Eye,” U.S. Securities and Exchange Commission, Jan. 2022, Exhibit 99.2 <https://www.sec.gov/Archives/edgar/data/0001314102/000156459022…
[cited by applicant]
EyePoint Pharmaceuticals, Inc. “Investor Presentation: Delivering Innovation to the Eye,” U.S. Securities and Exchange Commission, May 2022, Exhibit 99.1 <https://www.sec.gov/Archives/edgar/data/1314102/0001564590220200…
[cited by applicant]
EyePoint Pharmaceuticals, Inc. “Investor Day 2022,” U.S. Securities and Exchange Commission, Jul. 18, 2022, Exhibit 99.2 <https://www.sec.gov/Archives/edgar/data/1314102/000095017022012766/eypt-ex99_2.htm>.
[cited by applicant]
EyePoint Pharmaceuticals, Inc. “EyePoint Pharmaceuticals Reports Positive Interim Safety and Efficacy Data from Phase 1 DAVIO Clinical Trial Evaluating EYP-1901 for the Treatment of Wet AMD,” Form 8-K, Nov. 13, 2021.
[cited by applicant]
Gohil et al., “Studies On The Crosslinking of Poly (Vinyl Alcohol),” Journal of Polymer Research, 13:161-169 (2006).
[cited by applicant]
Hainsworth et al., “Intravitreal delivery of ciprofloxacin,” Journal of Ocular Pharmacology and Therapeutics, 12(2):183-191 (1996).
[cited by applicant]
Jackson et al., “Oral Tyrosine Kinase Inhibitor for Neovascular Age-Related Macular Degeneration: A Phase 1 Dose-Escalation Study,” JAMA Ophthalmology, 135(7):761-767 (2017).
[cited by applicant]
Jain et al., “Biodegradable hybrid polymeric membranes for ocular drug delivery,” Acta Biomaterialia, 6(4):1370-1379 (2010).
[cited by applicant]
Kurek E., “Oral Drug X-82 Shows Promise for Wet Age-Related Macular Degeneration,” HCP Live, Jul. 10, 2017 <https://www.hcplive.com/view/oral-drug-x82-shows-promise-for-wet-agerelated-macular-degeneration>.
[cited by applicant]
Lee et al., “Influence of drug release rate on systemic timolol absorption from polymeric ocular inserts in the pigmented rabbit,” Journal of Ocular Pharmacology and Therapeutics, 10(2):421-429 (1994).
[cited by applicant]
Makuuchi K. “Progress in radiation vulcanization of natural rubber latex,” International Nuclear Information System, 32(5):32-37 (2000).
[cited by applicant]
Peppas et al., “Ultrapure poly(vinyl alcohol) hydrogels with mucoadhesive drug delivery characteristics,” European Journal of Pharmaceutics and Biopharmaceutics, 43(1):51-58 (1997).
[cited by applicant]
Wan et al., “Drug release from heat-treated polyvinyl alcohol films,” Drug Development and Industrial Pharmacy, 18(17):1895-1906 (1992).
[cited by applicant]
Yang et al., “Reservoir-based polymer drug delivery systems,” Journal of Laboratory Automation, 17(1):50-58 (2012).
[cited by applicant]
Liang et al., “Vorolanib, a novel tyrosine receptor kinase receptor inhibitor with potent preclinical anti-angiogenic and anti-tumor activity,” Molecular Therapy Oncolytics, 24:577-584 (2022).
[cited by applicant]
Mallapragada et al., “Dissolution mechanism of semicrystalline poly(vinyl alcohol) in water,” Polymer Physics, 34(7):1339-1346 (1996).
[cited by applicant]
Peppas et al., “Semicrystalline poly(vinyl alcohol) films and their blends with poly(acrylic acid) and poly(ethylene glycol) for drug delivery applications,” Journal of Drug Delivery Science and Technology, 14(4):291-29…
[cited by applicant]
Abolian A., “Assessing Current Clinical Developments in Ophthalmic AAV Vector Gene Therapies Delivered by Subretinal & Suprachoroidal Injection,” Next Generation Drug Delivery Summit, Jan. 2023.
[cited by applicant]
Ali F., “Real World Use of Faricimab : An Iris Registry Analysis,” Hawaiian Eye 2023, 2023.
[cited by applicant]
Boyer et al., “The DAVIO Trial, Durasert and Vorolanib in Ophthalmology, Phase 1 Study Interim Results with EYP-1901,” American Academy of Ophthalmology (AAO) 2021 Annual Meeting, Nov. 2021.
[cited by applicant]
Creel J., “Investigating Subretinal Delivery via Suprachoroidal Cannulation,” Gyroscope Therapeutics, Jan. 26, 2023.
[cited by applicant]
Duker J., “8 month Results of a Tyrosine Kinase Inhibitor (Vorolanib) in a Bio erodible Durasert® Implant for Previously Treated Wet AMD: The DAVIO Trial,” Angiogenesis, 2022.
[cited by applicant]
Grisham R., “Development of Intravitreal Vector Delivery Modality for Gene Therapy as a New Standard of Care for Ocular Diseases,” Adverum, Jan. 2023.
[cited by applicant]
Gune S., “Port Delivery System With Ranibizumab,” Next Generation Ophthalmic Drug Delivery Summit, Jan. 2023.
[cited by applicant]
Hershberger et al., “Initial Safety Results of the DAVIO Trial: An Open Label, Dose Escalation Phase 1 Study of EYP-1901, a Tyrosine Kinase Inhibitor (TKI) in Subjects with Wet AMD,” ASRS, 2021.
[cited by applicant]
Jayagopal A., “Optimizing Subretinal Delivery of Gene Therapies,” OPUS Genetics, Jan. 2023.
[cited by applicant]
Kaiser P., “New Treatments for AMD Panel,” AMD Treatment Update, 2023.
[cited by applicant]
Patel et al., “EYP-1901: Open-label, Dose-Escalation Study Demonstrating Reduced Wet AMD Treatment Burden With Sustained TKI Inhibition—The DAVIO Trial,” Retina Society, 2022.
[cited by applicant]
Regillo C., “Port Delivery System Long term Portal Extension Data: Three Year Follow up From the Phase 3 Archway Study,” Hawaiian Eye, Jan. 2023.
[cited by applicant]
Saim S., “Exploring Zero-Order Release intraocular Formulations to Achieve Robust Sustained Efficacy,” Next Generation Ophthalmic Delivery Summit in San Francisco, Jan. 2023.
[cited by applicant]
Savinainen A., “Ocular Distribution and Exposure of Belzupacap Sarotalocan Following Intravitreal or Suprachoroidal Administration,” Next Generation Ophthalmic Drug Delivery Summit, Jan. 2023.
[cited by applicant]
Singh R., “12-Month Results of a Tyrosine Kinase Inhibitor (Vorolanib) in a Bioerodible Durasert® Insert for Previously Treated Neovascular AMD: The DAVIO Trial,” ASRS Annual Meeting—nAMD 2 Symposium, Jul. 2022.
[cited by applicant]
Singh R., “Targeting the Complement Cascade to Mitigate the Progression of Geographic Atrophy Secondary to AMD,” Retina 2023 CME Seminar, Jan. 2023.
[cited by applicant]
Stewart M., “Optimizing Clinical Trial Design to Deliver Desired Ocular Therapeutic Efficacy Duration,” Mayo Clinic Florida.
[cited by applicant]
Zilliox P., “Non-viral Gene Therapy Platform for the Treatment of Ocular Diseases,” EyeVensys, Jan. 2023.
[cited by applicant]
Blizzard et al., “Polymers for Retinal Drug Delivery,” Retinal Physician 20:28-31 (2023).
[cited by applicant]
EyePoint Pharmaceuticals, Inc. “Investor Presentation,” Sep. 28, 2022.
[cited by applicant]
Ren et al., “The Effect of CM082, an Oral Tyrosine Kinase Inhibitor, on Experimental Choroidal Neovascularization in Rats,” J Ophthalmol. 2017:6145651 (2017).
[cited by applicant]
Mashkovky M. D., “Drugs,” Physicians' Guide 14
[cited by applicant]