US Patent 11,413,323: Cyclosporine 0.1% Dry-Eye Treatment Scope, Validity and Patent Landscape

US Patent No. 11,413,323 protects selected methods of treating dry eye disease with a nonaqueous ophthalmic formulation containing 0.1% cyclosporine dissolved in 1-(perfluorobutyl)pentane, also known as perfluorobutylpentane, with up to about 1% ethanol. The claims are directed to specific patient populations, dosing, drop volume, clinical-response thresholds and symptom outcomes.

The patent is closely associated with Novaliq GmbH's cyclosporine ophthalmic product VEVYE, approved by the FDA in 2023 for the treatment of signs and symptoms of dry eye disease. The core commercial risk is not ordinary cyclosporine substitution. A competing product would need to avoid the claimed vehicle, dosing parameters, patient-selection limitations, or claimed treatment outcomes, or challenge the patent's validity.

What does US Patent 11,413,323 protect?

The patent protects treatment methods rather than a broad composition claim. Its central technical combination is:

Claim element	Claimed limitation
Active ingredient	0.1% w/v cyclosporine
Vehicle	1-(perfluorobutyl)pentane
Ethanol	Up to about 1.0% w/w
Administration	Topical administration to the eye
Frequency	Twice daily per eye
Drop volume	About 8 to 11 μL in claim 1; about 8 to 10 μL in claims 4, 9 and 16
Disease	Dry eye disease
Patient selection	OSDI score of at least 45 or, in narrower claims, at least 55
Clinical outcomes	Reduced corneal fluorescein staining, improved dryness, improved visual symptoms or reduced ocular-surface damage
Treatment period	Four or eight weeks in specified dependent claims

The patent therefore combines formulation, dosing regimen, patient stratification and efficacy limitations. Each limitation narrows literal infringement, but the combination can make design-around more difficult where a product is intended to match the VEVYE clinical and commercial profile.

What is the scope of independent claims 1, 9 and 16?

The three independent claims cover different commercial and clinical endpoints.

Independent claim	Primary protection	Required clinical limitation
Claim 1	Treatment of visual impairment or visual disturbance in severe dry-eye patients	At least 3-unit reduction in total corneal fluorescein staining
Claim 9	Treatment or amelioration of dryness symptoms	Reduction in frequency or severity of dryness within four weeks
Claim 16	Treatment of dry eye disease in a defined severe-disease population	Specific OSDI, staining and Schirmer's test criteria

Claim 1 is directed to visual symptoms, including blurred vision, photophobia, sore or painful eyes, reading difficulty, night-driving difficulty, computer use and television viewing. It requires an OSDI score of at least 45 and a reduction of at least three NEI-scale corneal fluorescein-staining units.

Claim 9 focuses on dryness symptoms and requires a patient with an OSDI score of at least 55 plus specified ocular-surface or tear-production characteristics. Claim 11 adds a 25% reduction threshold measured by visual analog scale testing.

Claim 16 is a broader treatment-method claim in subject matter but remains narrow in patient selection. It requires an OSDI score of at least 55 and at least one specified clinical criterion, including total corneal staining, central staining, lissamine green staining or unanesthetized Schirmer's test results.

Which patient populations are covered?

The patent targets patients with objectively and subjectively severe disease.

Patient-selection thresholds

The principal thresholds are:

OSDI score of at least 45 under claim 1.
OSDI score of at least 55 under claims 5, 9 and 16.
Total corneal fluorescein staining of 11 or higher in several claims.
Total staining in the range of 10 to 15 under claim 9.
Central corneal staining of 1 to 3, or more narrowly 2 to 3.
Lissamine green conjunctival staining of 2 to 6, or more narrowly 3 to 5.
Unanesthetized Schirmer's test of 2 to 8 mm.
Inferior corneal staining of at least 2 under claim 22.
Disease duration of at least six months under claim 21.
Aqueous-deficient or evaporative dry eye under claims 13, 14, 18 and 19.
Prior inadequate response to aqueous ophthalmic drops under claims 15 and 20.

These limitations create a potential enforcement issue. In ordinary commercial practice, a manufacturer controls the formulation, concentration, vehicle and dosing instructions. It may not control the patient's OSDI score, staining scores or response after treatment. Claims requiring post-treatment efficacy can still be asserted, but proof generally requires clinical, medical-record or product-use evidence.

What formulations are protected by the patent?

The protected formulation is a nonaqueous cyclosporine solution. The required composition contains:

Cyclosporine at 0.1% w/v.
1-(Perfluorobutyl)pentane as the solvent.
Up to approximately 1% w/w ethanol.

This distinguishes the claimed formulation from older aqueous or emulsion-based cyclosporine products.

Product or formulation type	Relationship to the patent
0.1% cyclosporine in perfluorobutylpentane	Within the central formulation limitation
0.05% cyclosporine ophthalmic emulsion	Different concentration and vehicle
0.09% cyclosporine ophthalmic solution	Different concentration and potentially different formulation
Aqueous cyclosporine formulation	Does not meet the claimed nonaqueous vehicle limitation
Cyclosporine in another fluorinated solvent	Potentially outside the literal vehicle limitation
Perfluorohexyloctane without cyclosporine	Different active ingredient and formulation

The patent does not, based on the supplied claims, broadly cover every cyclosporine ophthalmic product. The solvent identity is a critical limitation. A product containing cyclosporine in castor oil, an aqueous vehicle, an emulsion or a different semifluorinated alkane would require a separate infringement analysis.

When does US Patent 11,413,323 expire?

US Patent 11,413,323 issued on August 9, 2022. Its earliest identified priority date is March 24, 2016. On a standard 20-year patent-term calculation, the expected expiration date is approximately March 24, 2036, subject to patent-term adjustment, terminal disclaimers and any applicable patent-term extension.

Event	Date
Earliest priority date	March 24, 2016
Patent issue date	August 9, 2022
Expected base expiration	Approximately March 24, 2036
FDA product associated with the formulation	VEVYE
FDA approval date for VEVYE	May 18, 2023

The patent's exact enforceable expiration should be confirmed against the USPTO Patent Center term record and any issued certificate affecting patent-term adjustment. FDA regulatory exclusivity is separate from patent term.

What is the FDA and Orange Book status of the patent?

VEVYE, cyclosporine ophthalmic solution 0.1%, was approved under NDA 217670 for the treatment of signs and symptoms of dry eye disease.[1] FDA approval does not establish patent validity, but the approved product provides the regulatory reference for potential generic competition.

A patent covering an FDA-approved drug can be listed in the FDA's Approved Drug Products with Therapeutic Equivalence Evaluations, commonly called the Orange Book, if it claims the drug, a formulation, or an approved method of use and satisfies FDA listing requirements.[2] Method-of-use patents can be listed with a use code that identifies the protected indication or patient population.

For an ANDA applicant, a listed patent can trigger:

Paragraph III certification, accepting delayed entry until patent expiration.
Paragraph IV certification, asserting that the patent is invalid, unenforceable or will not be infringed.
A section viii statement seeking to omit the patented method from the proposed labeling, where the remaining labeling supports approval.

The commercial significance of a method-of-use listing depends on the breadth of the use code. A narrowly described indication can be carved out more readily than a use code that overlaps the principal labeled use of the reference product.

How could a generic applicant design around the patent?

A generic or competing cyclosporine product could target several limitations.

Formulation design-arounds

Potential design-around positions include:

Using an aqueous vehicle.
Using an emulsion.
Using a different fluorinated solvent.
Changing cyclosporine concentration from exactly 0.1% w/v.
Excluding ethanol or using a materially different ethanol amount.

The 0.1% concentration limitation may be particularly important. A formulation at 0.05%, 0.09% or another concentration would not literally satisfy that limitation, although the doctrine of equivalents could become relevant depending on the technical differences and prosecution history.

Dosing design-arounds

The claims specify twice-daily administration and an approximately 8 to 10 μL drop, or 8 to 11 μL in claim 1. A competing product using a materially different dosing frequency or drop volume could reduce literal infringement risk. That strategy must be balanced against clinical efficacy, device constraints and the need to obtain an FDA-approved label.

Patient-population design-arounds

A label that does not select patients by OSDI, corneal staining, lissamine green staining or Schirmer's test may reduce method-of-use exposure. The risk is higher where physicians routinely use the product in patients who meet the claimed criteria and the product's promotional materials identify those criteria.

Outcome-based limitations

Claims 1, 8, 9, 11 and 12 include clinical-response limitations. A challenger may argue that a product cannot infringe until the specified result occurs. The patent owner may respond that the claimed result is an inherent property of the claimed treatment when administered to the recited patient population.

How strong is the patent estate?

The patent has meaningful commercial strength because it connects four elements that competitors may need to reproduce: the cyclosporine concentration, the semifluorinated solvent, the twice-daily regimen and the severe-disease patient population.

Its principal vulnerabilities are claim-specific.

Strength factor	Assessment
Formulation specificity	Stronger than a broad cyclosporine claim because the vehicle is narrowly defined
Clinical differentiation	Strong where trial data support the claimed staining and symptom outcomes
Patient-selection limitations	Narrower enforceable scope but useful for targeted litigation
Written description	Potential issue for numerous outcome and subgroup combinations
Enablement	Potential issue if the full breadth of patient subgroups and claimed outcomes is not supported
Obviousness	Relevant prior art includes cyclosporine ophthalmic products, dry-eye clinical endpoints and nonaqueous ophthalmic vehicles
Infringement proof	More difficult for claims requiring patient scores and post-treatment outcomes
Regulatory leverage	Strongest if the patent is listed with a broad use code tied to the approved indication

The claims appear to rely heavily on clinical subgroup definition. That can support patentability when the subgroup and response were not predictable, but it also creates litigation exposure if the specification does not provide adequate data across the full claim scope.

Which competing drugs and patent estates matter?

Restasis

Restasis is cyclosporine ophthalmic emulsion 0.05%, associated with AbbVie and formerly Allergan. Its formulation differs materially from the claimed 0.1% cyclosporine solution in perfluorobutylpentane. Restasis patent litigation and regulatory exclusivity were central to earlier generic competition, but those issues do not eliminate the distinct formulation and method claims in US 11,413,323.

Cequa

Cequa is cyclosporine ophthalmic solution 0.09%, marketed by Sun Pharma. Its concentration and formulation differ from the patent's express 0.1% cyclosporine and perfluorobutylpentane limitations. Cequa is therefore a relevant competitive product but not necessarily a direct formulation substitute for VEVYE.

Xiidra

Xiidra, lifitegrast ophthalmic solution 5%, is an anti-inflammatory dry-eye product marketed by Bausch + Lomb. It does not contain cyclosporine and does not practice the claimed formulation. Its patent estate is commercially relevant to the dry-eye market but does not create direct formulation overlap.

Miebo

Miebo, perfluorohexyloctane ophthalmic solution, was approved for the signs and symptoms of dry eye disease associated with meibomian gland dysfunction. It is a nonaqueous fluorinated ophthalmic product but does not contain cyclosporine. Miebo illustrates the competitive value of fluorinated vehicles without, on the supplied claims, practicing the claimed cyclosporine combination.

What generic entry risks exist?

The most plausible entry scenarios are:

Scenario	Risk to VEVYE patent
Generic 0.05% cyclosporine emulsion	Low direct risk from this patent
Generic 0.09% cyclosporine solution	Lower formulation overlap, subject to vehicle analysis
0.1% cyclosporine in aqueous vehicle	Lower literal risk
0.1% cyclosporine in perfluorobutylpentane with the same dosing	High risk
Same formulation with a carved-out label	Depends on Orange Book use code and physician use
Same formulation with different drop volume	Reduced but not necessarily eliminated risk
Same formulation sold for a different indication	Risk remains if actual use meets a claimed method

The central litigation question would be whether an ANDA applicant's proposed label, product composition and expected use meet the formulation and regimen limitations. A Paragraph IV filing would likely challenge validity or noninfringement of the formulation-method combination, while a section viii strategy would attempt to omit the claimed dry-eye use.

What litigation and licensing issues affect the patent?

VEVYE was developed by Novaliq GmbH and commercialized in the United States through Harrow, Inc. The commercial relationship gives Harrow access to Novaliq's ophthalmic technology and VEVYE rights in the U.S. Novaliq has also entered licensing and collaboration arrangements concerning its EyeSol technology platform and ophthalmic products.[3]

The principal litigation risks are:

Paragraph IV litigation by an ANDA applicant.
A validity challenge based on obviousness over cyclosporine dry-eye therapy combined with nonaqueous ophthalmic vehicles.
Written-description or enablement attacks focused on the clinical subgroups and outcome limitations.
Noninfringement arguments based on vehicle, concentration, drop volume or dosing frequency.
Disputes over whether a patient-specific outcome limitation is satisfied by the accused product.
Patent-term or Orange Book listing challenges.

No conclusion about a specific pending Paragraph IV case or settlement should be inferred solely from the patent claims. The relevant sources are the current Orange Book, FDA litigation listings, PACER and USPTO records.

Key Takeaways

US Patent 11,413,323 is a method-of-treatment patent centered on 0.1% cyclosporine in perfluorobutylpentane.
It does not broadly cover all cyclosporine ophthalmic products.
The strongest commercial overlap is a product matching the 0.1% concentration, vehicle, twice-daily dosing and approximately 8 to 10 μL drop volume.
Claims 1, 9 and 16 target severe dry-eye populations using OSDI, corneal staining, lissamine green and Schirmer's test criteria.
Claims 9 through 12 add symptom and clinical-response thresholds that may strengthen differentiation but complicate infringement proof.
The expected base patent expiration is approximately March 24, 2036, subject to USPTO term adjustments.
Restasis and Cequa are important cyclosporine competitors but use different concentrations or formulation architectures.
Miebo is a relevant fluorinated-vehicle competitor but does not contain cyclosporine.
Generic risk is highest for a product that copies the VEVYE formulation and regimen, even if the applicant attempts to narrow the labeled patient population.
FDA regulatory exclusivity and patent exclusivity are separate and must be analyzed independently.

FAQs

Does US Patent 11,413,323 cover Restasis?

No. The supplied claims require 0.1% cyclosporine dissolved in 1-(perfluorobutyl)pentane. Restasis is a 0.05% cyclosporine ophthalmic emulsion with a different formulation.

Does the patent cover Cequa?

Not directly on the supplied claim language. Cequa contains 0.09% cyclosporine and uses a different formulation platform. The exact infringement analysis would depend on the accused product's vehicle, dosing and use.

Can a generic avoid the patent by using a 5 μL drop?

A materially smaller drop may avoid the express 8 to 10 μL or 8 to 11 μL limitations, but infringement would depend on the complete formulation, dosing instructions, patient population and potential equivalents analysis.

Are the claims limited to aqueous-deficient dry eye?

No. The claims expressly include aqueous-deficient and evaporative dry eye in dependent claims. The independent claims are not limited exclusively to one of those subtypes.

Does FDA approval prove that the patent is valid?

No. FDA approval and Orange Book listing are regulatory matters. Patent validity is determined under the Patent Act through USPTO examination, post-grant proceedings or federal-court litigation.

References

U.S. Food and Drug Administration. (2023). VEVYE (cyclosporine ophthalmic solution) 0.1% prescribing information.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations.
Harrow, Inc. (2023). Harrow announces FDA approval of VEVYE for the treatment of signs and symptoms of dry eye disease.
U.S. Patent and Trademark Office. (2022). U.S. Patent No. 11,413,323, methods of treating dry eye disease.
Novaliq GmbH. (2023). VEVYE and EyeSol ophthalmic technology materials.

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Harrow Eye	VEVYE	cyclosporine	SOLUTION;OPHTHALMIC	217469-001	May 30, 2023		RX	Yes	Yes	⤷ Start Trial	⤷ Start Trial				TREATMENT OF DRY EYE DISEASE (DED)	⤷ Start Trial
>Applicant	>Tradename	>Generic Name	>Dosage	>NDA	>Approval Date	>TE	>Type	>RLD	>RS	>Patent No.	>Patent Expiration	>Product	>Substance	>Delist Req.	>Patented / Exclusive Use	>Submissiondate

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2019358249	⤷ Start Trial
Canada	3112031	⤷ Start Trial
China	112823020	⤷ Start Trial
European Patent Office	3863658	⤷ Start Trial
European Patent Office	4406533	⤷ Start Trial
Spain	2974839	⤷ Start Trial
Israel	281773	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 11,413,323

Which drugs does patent 11,413,323 protect, and when does it expire?

Summary for Patent: 11,413,323