IP Library › Granted Patent US 12,364,680
Granted Patent B2
US 12,364,680 · App. 18/189,010 · Granted Jul 22, 2025

Compounds for treating ophthalmic diseases and disorders

Inventors: Stefan Sperl (Vienna, AT); Franz Obermayr (Vienna, AT)
Assignee: KIORA PHARMACEUTICALS GmbH
A61K31/381A61K9/0048A61K31/196A61K31/277A61K31/341A61K31/42A61K31/44A61K31/4418A61K31/47A61K31/4704A61K47/10A61K47/32A61K47/38
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 12,364,680
App. No.
18/189,010
Granted
Jul 22, 2025
Kind
B2
Abstract

The present invention relates generally to the field of ocular therapeutics and the development thereof for use in humans or animals. More particularly, it relates to DHODH inhibitor compounds and their use for the treatment of ophthalmic diseases and disorders. The invention also relates to the local administration of such ophthalmic compositions, and in particular to their intravitreal administration. The invention relates also to controlled release formulations of therapeutically active agents, in particular of DHODH inhibitor compounds administered intraocularly, in particular in the posterior segment of the eye.

Claims (17)

1. A method for treating an ocular disease with a hydroorotate dehydrogenase (DHODH) inhibitor compound, wherein the compound is 3-(2,3,5,6-tetrafluoro-3′-trifluoromethoxy-biphenyl-1-ylcarbamoyl)-thiophene-2-carboxylic acid and is represented by the following formula:

comprising administering by intravitreal injection a therapeutically effective amount of the compound to a subject in need thereof.

2. The method according to claim 1 , wherein the ocular disease is uveitis, dry eye, age-related macular degeneration (AMD), optic neuritis, retrobulbar neuritis, ocular inflammation or discomfort or trauma caused by or associated with the use of contact lenses, ocular inflammation, discomfort or trauma caused by or associated with the use of contact lenses, ocular inflammation, discomfort or trauma caused by or associated with refractive surgery, blepharitis, an optic nerve disease or disorder, or a conjunctivitis condition.

3. The method according to claim 2 , wherein the conjunctivitis condition is keratitis, keratoconjunctivitis, vernal keratoconjunctivitis (VKC), or atopic keratoconjunctivitis (AKC).

4. The method according to claim 1 , wherein the subject is suffering from uveitis, dry eye, age-related macular degeneration (AMD), or conjunctivitis.

5. The method according to claim 4 , wherein the subject is suffering from age-related macular degeneration (AMD).

6. The method according to claim 1 , wherein the ocular disease is caused by an adenovirus.

7. The method according to claim 1 , wherein said compound is administered to the subject at least once per day.

8. The method according to claim 1 , wherein said compound is administered at least once per month.

9. The method according to claim 1 , wherein the compound is formulated with a pharmaceutically acceptable excipient.

10. The method according to claim 9 , wherein the excipients are selected from the group consisting of hydrophilic polymer excipients, tonicity agents, buffers, sugars, preservatives, solvent and antioxidants.

11. The method according to claim 1 , wherein the compound is administered in a form selected from a sterile eye drop formulation, a suspension, an emulsion, a microsphere formulation, and a sterile solution.

12. The method of claim 1 , wherein the compound is formulated with an ophthalmically acceptable excipient.

13. The method according to claim 7 , wherein the compound is administered in the range of from about one to about eight times a day.

14. The method according to claim 1 , wherein the compound is administered to the posterior segment of the eye.

15. The method according to claim 1 , wherein the compound is administered at least every six months.

16. The method according to claim 10 , wherein the sugars are selected from the group consisting of trehalose, mannose, D-galactose, and lactose.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 24, 2023
From: SPERL, STEFAN; OBERMAYR, FRANZ
To: PANOPTES PHARMA GES.M.B.H.
Reel/Frame 063094/0347 →
CHANGE OF NAME Recorded Mar 24, 2023
From: PANOPTES PHARMA GES.M.B.H.
To: KIORA PHARMACEUTICALS GMBH
Reel/Frame 063620/0063 →
Priority Claims (2)
EP 14167490 · May 8, 2014 · regional
EP 14170616 · May 30, 2014 · regional
Continuity (2)
Continuation 15309176
Related Publication 20230285355A1 · Sep 14, 2023
References Cited (66)
US 6743826B1 · Hegedus et al. · 2004 [cited by applicant]
US 7365094B2 · Leban et al. · 2008 [cited by applicant]
US 7714132B2 · Fecher et al. · 2010 [cited by applicant]
US 8354433B2 · Vitt et al. · 2013 [cited by applicant]
US 9795590B2 · Strobl · 2017 [cited by applicant]
US 11730716B2 · Sperl · 2023 [cited by examiner]
US 12209073B2 · Sperl et al. · 2025 [cited by applicant]
US 20040176458A1 · Leban et al. · 2004 [cited by applicant]
US 20040192758A1 · Leban et al. · 2004 [cited by applicant]
US 20040254154A1 · Ashton · 2004 [cited by applicant]
US 20100280081A1 · Vitt et al. · 2010 [cited by applicant]
US 20110021465A1 · Minatelli et al. · 2011 [cited by applicant]
US 20110275603A1 · Muthuppalaniappan et al. · 2011 [cited by applicant]
US 20190025313A1 · Si et al. · 2019 [cited by applicant]
US 20210052737A1 · Sperl et al. · 2021 [cited by applicant]
US 20230278979A1 · Sperl et al. · 2023 [cited by applicant]
EP 0179477 · 1986 [cited by applicant]
EP 0413329 · 1991 [cited by applicant]
EP 0834320 · 1998 [cited by applicant]
JP 2006089485 · 2006 [cited by applicant]
JP 2009270356 · 2009 [cited by applicant]
WO WO99013914 · 1999 [cited by applicant]
WO WO2003006425 · 2003 [cited by applicant]
WO WO2004056746 · 2004 [cited by applicant]
WO WO2004056747 · 2004 [cited by applicant]
WO WO2004056797 · 2004 [cited by applicant]
WO WO2006022442 · 2006 [cited by applicant]
WO WO2007038687 · 2007 [cited by applicant]
WO WO2008077639 · 2008 [cited by applicant]
WO WO2009021696 · 2009 [cited by applicant]
WO WO2010128050 · 2010 [cited by applicant]
WO WO2011138665 · 2011 [cited by applicant]
WO WO2015154820 · 2015 [cited by applicant]
WO WO2022214691 · 2022 [cited by applicant]
Appeal Brief; filed Jan. 27, 2022; U.S. Appl. No. 15/309,176. [cited by applicant]
Examiner's Answer to Appeal Brief; Mailed Apr. 6, 2022; U.S. Appl. No. 15/309,176. [cited by applicant]
Reply Brief; filed Jun. 3, 2022; U.S. Appl. No. 15/309,176. [cited by applicant]
Affidavit/Declaration/ Exhibit After Notice of Appeal; filed Dec. 2, 2022; U.S. Appl. No. 15/309,176. [cited by applicant]
Patent Board Decision—Examiner Reversed; Mailed Dec. 21, 2022; U.S. Appl. No. 15/309,176. [cited by applicant]
Notice of Allowance and Fees Due (PTOL-85); Mailed Mar. 8, 2023; U.S. Appl. No. 15/309,176. [cited by applicant]
Castiblanco et al., 2014, Review of systemic immunosuppression for autoimmune uveitis, Ophthalmol Ther, 3:17-36. [cited by applicant]
Diedrichs-Mohring et al., 2018, Intraocular DHODH-inhibitor PP-001 suppresses relapsing experimental uveitis and cytokine production of human lymphocytes, but not of RPE cells J. of Neuroinflammation, 15(54):1-11. [cited by applicant]
Fang et al., Apr. 2013, Amelioration of Experimental Autoimmune Uveitis by Leflunomide in Lewis Rats, PLoS ONE 8(4):e62071. [cited by applicant]
Kompella at el., 2011, Drug Product Development for the Back of the Eye, Springer, New York (TOC). [cited by applicant]
Marschall et al.,, 2013, Assessment of drug candidates for broad-spectrum antiviral therapy targeting cellular pyrimidine biosynthesis, Antiviral Research, 100(3):640-648 with supporting information. [cited by applicant]
Peyman et al., 2009, Intravitreal injection of therapeutic agents, retrieved from internet: https://insights.ovid.com/pubmed?pmid=19584648, 1 p. [cited by applicant]
Suhler et al., Jul. 2018, Safety and Efficacy of Adalimumab in Patients with Noninfectious Uveitis in an Ongoing Open-Label Study: Visual III, Ophthalmology, 125(7):1075-1087. [cited by applicant]
Sung et al., 1999, Intravitreal controlled release implant for leflunomide: Potential treatment for uveitis, Proceedings of he International Symposium on Controlled Release of Bioactive Materials, 26:38-39. [cited by applicant]
Yeh et al., 2019, Suprachoroidal injection of triamcinolone acetonide, CLS-TA, for macular edema due to noninfectious uveitis, Retina 39(10):1880-1888. [cited by applicant]
Written Opinion for PCT/EP2015/060166 of Panoptes Pharma GES, M.B.H., (Dec. 11, 2015). [cited by applicant]
Berge et al., Jan. 1977, Pharmaceutical Salts, J. Pharm. Sci., 66(1):1-19. [cited by applicant]
Brittain, Dec. 1, 2009, Developing an appropriate salt form for an active pharmaceutical ingredient, American Pharmaceutical Review, 12(7):62-65. [cited by applicant]
CAS Registry No. 717142-73-9. Accessed Dec. 4, 2023, 2 pp. [cited by applicant]
Chong et al., 2006, Concurrent Antiviral and Immunosuppresive Activites of Leflunomide In Vivo, Am. J. Transplant, 5(1):69-75. [cited by applicant]
Kindsmuller et al., Sep. 2009, A 49-Kilodalton Isoform of the Adenovirus Type 5 Early Revion 1B 55-Kilodalton Protein Is Sufficient to Support Virus Replication, J. Viral. 83(18):9045-9056. [cited by applicant]
Klein, 2010, The use of biorelevant dissolution media to forecast the in vivo performance of a drug, The AAPS Journal, 12(3):397-406. [cited by applicant]
Marschall et al., 2012, In Vitro Evaluation of the Activies of the Novel Anticytomegalovirus Compound AIC246 letermovir) against Herpesviruses and other Human Pathogenic Viruses, Antimicrob. Agents Chemother. 56:1135-11… [cited by applicant]
Meister, 2005, Antiviral Mechanism(s) of the Experimental Immunosuppressive Agent Leflunomide Against Human Cytomegalovirus and Polyomavirus, doctoral dissertation, Ohio State University, 141 pp. [cited by applicant]
Schuerer et al., May 7-11, 2017, Ocular toxicity and ocular tissue distribution of topically applied PP-001 in vivo, Abstract from the Annual Meeting of the Association for Research in Vision and Ophthalmology, Baltimor… [cited by applicant]
Shimmura et al., 2003, Albumin as a tear supplement in the treatment of sever dry eye, Br. J Ophthalmology, 87:1279-1283. [cited by applicant]
Supporting information for Marschall, Manfred, et al. “Assessment of Drug Candidates for Broad-Spectrum Antiviral Therapy Targeting Cellular Pyrimidine Biosynthesis.” Antiviral Research, vol. 100, No. 3, Dec. 2013, pp. … [cited by applicant]
Yamasaki et al., 2013, Albumin-drug interaction and its clinical implication. Biochim Biophys Acta, 1830(12):543505443. [cited by applicant]
Baumgartner et al., 2006, Dual Binding Mode of a Novel Series of DHODH Inhibitors Journal of Medicinal Chemistry, 49(4):1239-1247. [cited by applicant]
Davis et al., 1996, The Immunosuppressive Metabolite of Leflunomide is a Potent Inhibitor of Human Dihydroorotate Dehydrogenase, Biochemistry, 35(4):1270-1273. [cited by applicant]
Leban et al., 2006, Biphenyl-4-ylcarbamoyl thiophene carboxylic acids as potent DHODH inhibitors, Bioorg Med Chem cell., 16(2):267-270. [cited by applicant]
Rechter et al., 2006, Antiviral activity of Arthrospira-derived spirulan-like substances, Antiviral Res. 72:197-206. [cited by applicant]