United States Patent 4,839,342: Scope, Claims, Expiration, and Cyclosporine Dry-Eye Patent Landscape

U.S. Patent No. 4,839,342 covers topical ophthalmic administration of cyclosporin to enhance or restore tear production, including treatment of tear-deficient eyes, autoimmune lacrimal-gland dysfunction, keratoconjunctivitis sicca, and disorders worsened by inadequate tears. The patent issued June 13, 1989, and its enforceable term expired in 2006. It does not create a current barrier to generic cyclosporine ophthalmic products.

The patent is important historically because it established the core therapeutic concept later commercialized in cyclosporine ophthalmic products such as Restasis. Its claims are method-of-treatment claims, not composition, manufacturing, device, or formulation claims. Current commercial risk therefore depends on later patents covering specific emulsions, concentrations, excipients, dosing regimens, and products rather than on U.S. Patent 4,839,342.

What does U.S. Patent 4,839,342 protect?

The patent protects a treatment method in which cyclosporin is administered topically to the eye to increase, enhance, or restore lacrimal gland tear production. The central claim elements are:

Claim element	Scope
Active ingredient	“Cyclosporin,” with dependent claims specifically reciting Cyclosporin A
Route	Topical administration to the eye
Therapeutic objective	Enhancing or restoring tearing or increasing tear production
Patient condition	Tear-deficient eye, autoimmune lacrimal-gland dysfunction, keratoconjunctivitis sicca, or disorders caused or exacerbated by deficient tear production
Formulation	Solution, suspension, ointment, or other ophthalmic vehicle
Concentration	0.01% to 50% by weight in certain dependent claims; 0.1% to 20% in narrower claims
Vehicle	Listed oils, mineral oil, petroleum jelly, dimethyl sulfoxide, alcohol, liposomes, silicone fluid, or mixtures

The broadest independent claim is claim 1. It requires:

A method;
Topical administration;
Cyclosporin;
Administration to the eye; and
Enhancement or restoration of lacrimal gland tearing.

Claims 2 through 18 are dependent claims that add therapeutic, formulation, concentration, vehicle, or disease limitations.

How are the claims structured?

Claim 1: Broad therapeutic method

Claim 1 is the broadest claim. It does not specify:

Cyclosporin A;
A particular concentration;
A particular vehicle;
A particular dry-eye diagnosis;
A particular dosing frequency; or
A particular formulation technology.

A product or treatment falling within claim 1 would need to involve topical cyclosporin administration for the purpose of enhancing or restoring lacrimal gland tearing.

The claim is narrower than a claim to any topical cyclosporin use because it requires the stated tear-production objective. It also does not cover systemic administration, oral administration, intravenous administration, or non-ocular topical use.

Claim 2: Tear-deficient eyes

Claim 2 adds the limitation of increasing tear production in a tear-deficient eye and requires a therapeutically effective amount. It remains broad as to:

Cyclosporin species;
Dosage form;
Excipient;
Concentration; and
Cause of tear deficiency.

Claims 3 through 5: Formulation and concentration limitations

Claims 3 through 5 create a narrower formulation group:

Claim 3 covers a solution, suspension, or ointment containing 0.01% to 50% cyclosporin by weight.
Claim 4 narrows that range to 0.1% to 20%.
Claim 5 identifies specific excipients and vehicle classes.

These claims are composition-dependent method claims. They do not independently claim the formulation as a product. Infringement would require both the formulation characteristics and the claimed therapeutic administration.

Claim 6: Cyclosporin A

Claim 6 narrows claim 2 to Cyclosporin A. This is commercially significant because cyclosporine ophthalmic products generally use cyclosporine, also known as cyclosporin A, as the active ingredient.

Claims 7 through 13: Autoimmune lacrimal-gland disease and keratoconjunctivitis sicca

Claims 7 through 13 address:

Autoimmune dysfunction of the lacrimal glands;
Keratoconjunctivitis sicca;
Disorders caused by immune activity in the lacrimal gland;
Cyclosporin A; and
The formulation and vehicle limitations from earlier claims.

These claims provide disease-specific alternatives to the general tear-production claims. They also make the patent relevant to modern dry-eye terminology, including aqueous-deficient dry eye associated with immune-mediated lacrimal-gland dysfunction.

Claims 14 through 18: Disorders worsened by deficient tearing

Claims 14 through 18 cover treatment of a disorder exacerbated by deficient tear production. These claims may reach conditions other than dry eye if deficient tearing worsens the condition and the treatment is directed to enhancing or restoring tearing.

The phrase “exacerbated by deficient tear production” expands the disease context, but the claims still require topical cyclosporin administration and a tear-restoration purpose.

What is the strongest claim in U.S. Patent 4,839,342?

Claim 1 is the strongest claim in terms of breadth because it has no express concentration, vehicle, disease, or Cyclosporin A limitation. Its principal vulnerability is functional and interpretive: the accused treatment must be directed to enhancing or restoring lacrimal gland tearing.

Claims 2, 7, 8, 9, and 14 are narrower therapeutic alternatives. Claims 3 through 5, 10 through 12, and 15 through 17 are narrower formulation claims. Claims 6, 13, and 18 are limited to Cyclosporin A.

Claim group	Principal limitation	Relative breadth
Claim 1	Topical cyclosporin for enhancing or restoring tearing	Broadest
Claim 2	Tear-deficient eye and increased tear production	Broad
Claims 3-5	Concentration, dosage form, and excipients	Narrow
Claim 6	Cyclosporin A	Narrower
Claims 7-9	Autoimmune dysfunction, keratoconjunctivitis sicca, or immune activity	Disease-specific
Claims 10-13	Disease-specific claims plus formulation limits or Cyclosporin A	Narrow
Claims 14-18	Disorders exacerbated by deficient tearing	Disease-context specific

When did U.S. Patent 4,839,342 expire?

U.S. Patent 4,839,342 expired in 2006 under the pre-URAA patent-term regime, which generally provided 17 years from issuance for patents of this vintage. The patent issued on June 13, 1989, placing the ordinary expiration date in June 2006. The patent is therefore expired and cannot support an infringement action against current U.S. products.

Event	Date or status
Patent issued	June 13, 1989
Governing term framework	Pre-1995, generally 17 years from issuance
Approximate expiration	June 2006
Current enforceability	Expired
Current U.S. blocking effect	None

Patent expiration removes the exclusionary right, but it does not erase the patent’s technical disclosure. The patent remains relevant as prior art against later applications claiming the same basic use of topical cyclosporine for tear production. The disclosure can also affect novelty and obviousness analyses for later method and formulation patents. [1][2]

Was U.S. Patent 4,839,342 an Orange Book patent?

U.S. Patent 4,839,342 is not a current Orange Book barrier. The Orange Book identifies patents submitted by sponsors for approved drug products, but listing practices depend on the patent’s relationship to the approved product and on the patent’s expiration and regulatory status. The patent’s 2006 expiration makes it commercially inactive for present-day generic approval disputes.

Orange Book-listed patents for cyclosporine ophthalmic products were associated primarily with later formulation and product patents, including patents relating to ophthalmic emulsions and specific commercial products. The relevant listing and litigation record must be evaluated product by product because Restasis, generic cyclosporine ophthalmic emulsion, and other cyclosporine products may have different listed patents. [3]

What later patents protected cyclosporine ophthalmic products?

The post-4,839,342 patent landscape shifted from the basic therapeutic concept to formulation engineering and product-specific delivery systems. Later patent categories included:

Patent category	Typical protected subject matter
Ophthalmic composition patents	Emulsions, suspensions, solubilized cyclosporine, and excipient systems
Particle-size patents	Droplet or particle size distributions affecting stability and ocular delivery
Preservative-free formulations	Single-use containers and sterile unit-dose systems
Dosing patents	Administration frequency and treatment schedules
Product-specific methods	Treatment of dry-eye disease with an approved formulation
Manufacturing patents	Emulsification, homogenization, sterilization, and filling processes
Device and packaging patents	Containers, unit-dose delivery, and multidose dispensers

The original patent disclosed broad excipient classes, including oils, liposomes, silicone fluids, and polyoxyethylated castor oil. Later patents could still obtain protection if they claimed a technically distinct composition, a defined microstructure, a specific excipient ratio, a narrow particle-size profile, or a manufacturing process not disclosed or rendered obvious by the earlier patent.

The existence of a later patent does not mean that every cyclosporine ophthalmic product remains blocked. A product must be compared against the later patent’s issued claims, including all concentration, excipient, particle-size, packaging, and process limitations.

How did the patent relate to Restasis?

Restasis, an ophthalmic cyclosporine emulsion approved by the FDA in 2003, commercialized the therapeutic approach described in U.S. Patent 4,839,342. The product’s FDA-approved indication is to increase tear production in patients whose tear production is suppressed due to ocular inflammation associated with keratoconjunctivitis sicca. [4]

The commercial distinction is important:

U.S. Patent 4,839,342 claimed the broad therapeutic use.
Later patents focused on the commercial formulation and product implementation.
Restasis regulatory exclusivity and later patent protection were separate from the expired 4,839,342 patent.
Generic competition primarily implicated the later product and formulation patents, not the expired foundational method patent.

The Restasis label identifies cyclosporine ophthalmic emulsion as a topical ophthalmic product. It also states that the product is administered as one drop in each eye twice daily, approximately 12 hours apart. [4]

Were there Paragraph IV challenges involving cyclosporine ophthalmic products?

Yes. Generic applicants challenged patents associated with Restasis through ANDA Paragraph IV certifications. The principal disputes concerned later patents covering the Restasis formulation and methods of use, rather than U.S. Patent 4,839,342.

A Paragraph IV certification asserts that a listed patent is invalid, unenforceable, or would not be infringed by the proposed generic product. A sponsor’s patent litigation can trigger the Hatch-Waxman 30-month stay, subject to statutory conditions and court rulings. [5]

The relevant commercial consequences included:

Delayed generic approval or launch;
Litigation over formulation and method claims;
Settlements that could establish an agreed generic-entry date;
Risk that some claims would survive while others were invalidated or narrowed; and
Different outcomes for different ANDA applicants.

Because U.S. Patent 4,839,342 expired decades ago, it could not provide the basis for a current Paragraph IV delay. Any present dispute must arise from unexpired patents listed against the relevant reference product.

Which companies challenged cyclosporine ophthalmic patents?

The commercial challengers were generic pharmaceutical companies pursuing ANDAs for cyclosporine ophthalmic emulsion. Notable market participants have included Mylan, Teva, Apotex, and other generic developers, depending on the specific product, dosage form, and approval period.

The principal branded sponsor associated with Restasis was Allergan, later acquired by AbbVie. The patent disputes involved the sponsor’s later Orange Book-listed patents and the generic applicants’ noninfringement, invalidity, and unenforceability positions.

A complete company-by-company litigation analysis requires separating:

Restasis litigation;
Generic cyclosporine ophthalmic emulsion approvals;
Patents listed against the reference listed drug;
Individual ANDA applicants;
Court outcomes; and
Settlement or launch dates.

The expired 4,839,342 patent does not materially change that analysis.

What generic entry risks remain for cyclosporine ophthalmic products?

The main current risks are formulation and regulatory risks, not the original therapeutic-use patent.

Formulation risk

A generic applicant may need to demonstrate pharmaceutical equivalence or otherwise satisfy FDA requirements for a complex ophthalmic emulsion. Differences in droplet size, inactive ingredients, viscosity, osmolality, pH, container closure, and preservative status can affect approval strategy and patent exposure.

Method-of-use risk

A generic label that includes the same dry-eye indication may implicate unexpired method-of-use patents if those patents remain listed and valid. A section viii “skinny label” strategy may avoid a patented indication in some circumstances, but it depends on the scope of the listed claims and the proposed labeling.

Manufacturing risk

Cyclosporine is poorly water-soluble. Achieving a stable ophthalmic product requires control of dispersion, emulsion stability, sterility, droplet size, and container compatibility. A manufacturing patent may create a separate risk even if the finished-product claims are avoided.

Regulatory risk

FDA approval of a generic ophthalmic product does not automatically resolve patent infringement risk. Approval and patent clearance are separate legal questions. The Orange Book, FDA labeling, ANDA certification, and applicable court orders must be reviewed together. [3][5]

Does cyclosporine create biosimilar risk?

No. Cyclosporine is a small-molecule immunosuppressant, not a biologic. Products containing cyclosporine are reviewed through small-molecule drug pathways, generally under an ANDA where the statutory requirements are met. Biosimilar litigation and the Biologics Price Competition and Innovation Act do not apply.

The relevant competitive framework is generic substitution, formulation differentiation, and patent litigation under the Hatch-Waxman Act.

How strong is the patent estate associated with U.S. Patent 4,839,342?

The standalone estate is legally weak today because the patent expired in 2006. Its historical strength was substantial at the conceptual level because it claimed the core use of topical cyclosporin to restore tear production before the commercial dry-eye cyclosporine market developed.

Factor	Assessment
Original therapeutic breadth	High
Formulation specificity	Moderate to low in the broad claims
Disease coverage	Broad, with specific dependent alternatives
Current enforceability	None
Prior-art value	High for later topical cyclosporine tear-treatment claims
Current generic blocking power	None
Biosimilar relevance	None
Commercial importance	Foundational and historical

The patent’s principal continuing value is evidentiary. Later applicants cannot treat the underlying therapeutic concept as new merely by selecting Cyclosporin A, a conventional ophthalmic vehicle, or a routine dry-eye indication unless the later claim includes a patentably distinct limitation.

How does U.S. Patent 4,839,342 compare with later formulation patents?

Issue	U.S. Patent 4,839,342	Later cyclosporine formulation patents
Claim type	Method of treatment	Composition, method, manufacturing, or device
Core subject	Topical cyclosporin for tear restoration	Specific formulation or product implementation
Concentration	Broad ranges in dependent claims	Often narrower and product-specific
Vehicle	Broad list of excipients	Defined excipient ratios and emulsion structures
Product identity	Not limited to Restasis	Often tied to a commercial formulation
Expiration	2006	Varied by patent and patent-term adjustments
Generic relevance	Historical only	Potentially current, depending on expiration
Regulatory connection	Foundational disclosure	Often linked to Orange Book-listed products

Key Takeaways

U.S. Patent 4,839,342 covers topical cyclosporin treatment to enhance or restore lacrimal gland tearing.
Claim 1 is the broadest claim and does not require Cyclosporin A, a particular concentration, or a specific vehicle.
Dependent claims cover tear-deficient eyes, autoimmune lacrimal-gland dysfunction, keratoconjunctivitis sicca, specified concentration ranges, excipients, and Cyclosporin A.
The patent expired in approximately June 2006 under the pre-URAA 17-year-from-issuance term.
It is not a current barrier to generic cyclosporine ophthalmic products.
Later commercial disputes focused on Restasis formulation, product, method-of-use, manufacturing, and related patents.
Cyclosporine is a small molecule, so biosimilar rules do not apply.
Current generic-entry risk depends on unexpired Orange Book-listed patents, formulation equivalence, method-of-use labeling, and manufacturing claims.

FAQs About U.S. Patent 4,839,342 and Cyclosporine Ophthalmic Patents

Is U.S. Patent 4,839,342 still enforceable?

No. The patent expired in 2006 and cannot support a current infringement claim.

Does the patent cover all uses of cyclosporine in the eye?

No. It covers topical ocular administration directed to enhancing or restoring lacrimal gland tearing. It does not cover every ophthalmic, intraocular, or non-ocular use of cyclosporine.

Does the patent claim Restasis as a composition?

No. Its claims are method claims. They do not claim the Restasis emulsion as a standalone composition.

Can a generic manufacturer rely on the expiration of this patent?

Yes, as to this patent. The manufacturer must still assess later unexpired patents listed for the relevant reference product and the claims of any asserted formulation, method, manufacturing, or device patents.

Is keratoconjunctivitis sicca the only disease covered?

No. The claims also address tear-deficient eyes, autoimmune lacrimal-gland dysfunction, immune-mediated lacrimal-gland disorders, and disorders exacerbated by deficient tear production.

References

United States Patent and Trademark Office. (1989). U.S. Patent No. 4,839,342, Method for treating lacrimal gland dysfunction.
United States Patent and Trademark Office. (2024). Manual of Patent Examining Procedure, Chapter 2700: Patent term.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book.
U.S. Food and Drug Administration. (2023). Restasis (cyclosporine ophthalmic emulsion) prescribing information. AbbVie Inc.
U.S. Food and Drug Administration. (2024). Hatch-Waxman amendments and abbreviated new drug applications.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	109970	⤷ Start Trial
Australia	2421388	⤷ Start Trial
Australia	620048	⤷ Start Trial
Canada	1335566	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 4,839,342

Summary for Patent: 4,839,342