United States Patent 4,559,343: Suprofen Ophthalmic Composition Claims, Expiration, and Patent Landscape

U.S. Patent No. 4,559,343 covers ophthalmic compositions that combine suprofen or other topical nonsteroidal anti-inflammatory agents with a low concentration of a xanthine derivative, particularly caffeine, to reduce ocular stinging and discomfort. The patent issued on December 17, 1985, and, under the pre-Uruguay Round patent term applicable to the patent, expired no later than December 17, 2002. Its claims are no longer enforceable against generic, branded, or reformulated products.

The patent remains relevant as a prior-art reference for ophthalmic NSAID formulations, but it does not create a current barrier to manufacture, approval, licensing, or launch.

What does U.S. Patent 4,559,343 protect?

The patent protects two related subject matter groups:

An aqueous ophthalmic composition containing suprofen, a xanthine derivative, a preservative, and a buffer.
A method of reducing stinging from topical ophthalmic NSAIDs by adding a xanthine derivative to the aqueous formulation.

The disclosed formulation concept is the use of the xanthine derivative as a comfort-enhancing excipient rather than as the anti-inflammatory active ingredient.

Core composition claim

Claim 1 requires all of the following:

Limitation	Requirement
Dosage form	Aqueous ophthalmic composition
Therapeutic active	Su profen in a therapeutically effective amount
Indication	Topical treatment of ocular inflammation
Comfort agent	Theophylline, caffeine, theobromine, or a mixture
Xanthine concentration	An amount sufficient to reduce discomfort, subject to the stated solubility and 0.05% w/v limitation
Preservative	Ophthalmic preservative
Buffer	Buffer sufficient to provide the claimed formulation characteristics
Physical properties	Isotonic, nonirritating, nonsteroidal composition

Claim 2 narrows claim 1 by requiring caffeine as the xanthine derivative.

Claim 3 further narrows the composition by requiring suprofen at approximately 0.5% to 3.0% weight/volume.

A product would therefore fall within the literal scope of claim 3 only if it contained suprofen within that concentration range, caffeine within the claimed functional and quantitative range, and the other required formulation elements.

Method claims

Claim 4 is broader in its anti-inflammatory-agent coverage. It covers adding a specified xanthine derivative to an aqueous solution containing one of a long list of NSAIDs, including:

Mefenamic acid
Flufenamic acid
Clonixin
Flufenisal
4-(tert-butyl)benzeneacetic acid
Ibufenac
Ibuprofen
Alclofenac
Feneprofen
Naproxen
Indomethacin
Tolmetin
Flurbiprofen
Ketoprofen
Namoxyrate
Suprofen
Pharmaceutically acceptable salts of the listed acids

Claim 5 narrows claim 4 to theophylline, caffeine, theobromine, or mixtures. Claim 6 narrows the method to suprofen and caffeine. Claim 7 adds the 0.5% to 3.0% suprofen concentration range.

The method claims do not expressly repeat every composition limitation appearing in claim 1. In particular, claims 4 through 7 do not expressly require a preservative, buffer, or isotonicity in the same manner as claim 1. They do require an aqueous solution that forms a nonirritating ophthalmic composition.

How broad is the xanthine derivative coverage?

The patent has two different xanthine definitions.

Claims 1 through 3 identify the xanthine derivative by name:

Theophylline
Caffeine
Theobromine
Mixtures of those compounds

Claim 4 uses a structural definition covering substituted xanthines in which each of R1, R2, and R3 is hydrogen, methyl, or ethyl, with at least two substituents selected from methyl or ethyl. Claims 5 through 7 then narrow that structural genus back to the three named compounds.

The practical claim scope is therefore:

Claim group	Xanthine scope	Practical breadth
Claims 1-3	Theophylline, caffeine, theobromine, mixtures	Narrow named-compound scope
Claim 4	Defined methyl- or ethyl-substituted xanthine genus	Broadest xanthine scope
Claims 5-7	Theophylline, caffeine, theobromine, mixtures	Narrower method scope

The concentration limitation is material. The claims do not cover every amount of caffeine or every xanthine derivative concentration. The xanthine must be present in an amount that reduces discomfort and within the claimed relationship to aqueous solubility, with an upper limit of 0.05% w/v.

What suprofen concentrations are protected?

Claims 3 and 7 identify a suprofen range of approximately 0.5% to 3.0% w/v. The range is narrower than the independent claims because claims 1 and 6 do not impose that numeric concentration limitation.

A formulation containing suprofen below 0.5% or above 3.0% could still raise issues under claims 1 or 6 if it otherwise met those claims. It would not, however, satisfy the express concentration limitation of claims 3 or 7.

The patent does not claim suprofen alone. The claimed invention depends on the combination of:

An aqueous ophthalmic vehicle;
Su profen or another listed ophthalmic NSAID;
A low-level xanthine derivative;
A functional reduction in stinging or discomfort; and
For claim 1, a preservative and buffer in an isotonic composition.

What is the legal status and expiration date of U.S. Patent 4,559,343?

U.S. Patent 4,559,343 is expired. The patent issued on December 17, 1985. Because it was governed by the pre-June 8, 1995 patent-term regime, its ordinary term was 17 years from grant rather than 20 years from the earliest effective filing date. The resulting expiration date was December 17, 2002, absent an unusual terminal disclaimer or other term adjustment reflected in the official record. No enforceable patent rights remain under the patent today. (United States Patent and Trademark Office, 1985)

Event	Date
Patent issued	December 17, 1985
Ordinary pre-URAA term	17 years from issue
Expiration	December 17, 2002
Current enforceability	Expired

The expired status eliminates infringement exposure based on the patent itself. It does not eliminate potential issues under later patents covering a different active ingredient, formulation, delivery system, manufacturing process, or method of treatment.

What formulation patents are relevant to this patent?

The patent is a formulation-improvement patent. Its principal technical contribution is not the discovery of suprofen as an NSAID, but the use of a xanthine derivative to reduce ocular discomfort associated with topical NSAID administration.

The main formulation limitations are:

Aqueous vehicle

The composition must be aqueous. An anhydrous ophthalmic ointment, suspension, emulsion, gel, or solid implant would not meet the aqueous limitation without satisfying the claim through a properly construed aqueous phase.

Nonirritating and isotonic properties

Claim 1 expressly requires an isotonic, nonirritating ophthalmic composition. These terms create potential claim-construction and proof issues because they depend on formulation testing and the patent specification’s technical disclosure.

Preservative

Claim 1 requires an ophthalmic preservative. A preservative-free single-dose product would not literally satisfy this limitation unless the preservative requirement were otherwise met or a court applied an expansive doctrine-of-equivalents analysis. Because the patent is expired, this issue has historical and prior-art significance rather than current enforcement significance.

Buffer

Claim 1 requires a buffer. A formulation using pH adjustment without a conventional buffer system could present a claim-scope distinction, depending on the formulation chemistry and claim construction.

Xanthine comfort agent

The xanthine derivative is the central differentiating formulation element. A product using another anesthetic, surfactant, polymer, cyclodextrin, or pH-modifying agent to reduce stinging would not literally satisfy the xanthine limitation.

What method-of-use patents does the patent cover?

Claims 4 through 7 cover the method of adding the xanthine derivative to an aqueous ophthalmic NSAID solution to reduce stinging and discomfort.

The method claims are functional. The xanthine derivative must be present in an amount effective to reduce discomfort. A mere formulation containing caffeine would not necessarily satisfy the full method claim unless it was used in the claimed manner and produced the required comfort-reduction result.

The method claims cover a broad NSAID list, but they do not cover every ocular anti-inflammatory drug. Agents developed after the patent, including later-generation ophthalmic NSAIDs, would require separate analysis unless they fall within an express listed compound, a salt, or a relevant claim-construction theory.

What is the FDA and Orange Book status?

The patent is not a current Orange Book barrier.

FDA Orange Book listings generally matter when a patent is listed against an approved drug product and can support a Paragraph IV certification or a 30-month stay in abbreviated new drug application litigation. An expired patent cannot create a current statutory stay or prevent approval based on its former listing. (U.S. Food and Drug Administration, 2024)

Suprofen ophthalmic products are not a significant current U.S. generic market category. The historical commercial product associated with suprofen ophthalmic therapy was Profenal. The product’s commercial discontinuation and the absence of an enforceable patent estate materially reduce the relevance of Patent 4,559,343 to present-day ANDA strategy.

Regulatory issue	Status
Current enforceable patent	None under U.S. Patent 4,559,343
Current Paragraph IV risk from this patent	None
Current 30-month stay risk from this patent	None
Current Orange Book exclusivity created by this patent	None
Historical relevance	Prior art for ophthalmic NSAID comfort formulations

FDA approval status, commercial availability, and Orange Book listing status are separate from patent expiration. A company would still need an appropriate FDA regulatory pathway for a suprofen ophthalmic product, including consideration of reference-product availability, discontinued-drug status, bioequivalence, chemistry and manufacturing controls, and any required clinical or bridging data.

When did suprofen lose exclusivity?

Patent-based exclusivity under U.S. Patent 4,559,343 ended in December 2002. Any regulatory exclusivity associated with the original approval would have expired much earlier or independently of the patent.

The patent did not provide a 20-year term from filing because it was issued under the older patent-term regime. Later patents cannot be assumed to extend the term of Patent 4,559,343. A later patent would need to claim a separate invention, such as a different formulation, delivery system, manufacturing process, or therapeutic use.

Which companies are challenging the patent?

No current Paragraph IV challenge is material because the patent expired in 2002. A Paragraph IV certification against an expired patent would have no practical ability to delay approval through the Hatch-Waxman 30-month-stay mechanism.

The publicly relevant competitive set is not made up of companies challenging this patent. It consists of manufacturers and sponsors of alternative ophthalmic NSAIDs, including products based on:

Ketorolac
Diclofenac
Flurbiprofen
Nepafenac
Bromfenac

These products rely on their own active-ingredient, formulation, manufacturing, and use patents. Their patent estates are separate from the expired suprofen-caffeine claims.

How does Patent 4,559,343 compare with competing ophthalmic NSAID patent estates?

Product or active ingredient	Typical patent focus	Relationship to Patent 4,559,343
Suprofen ophthalmic	Su profen composition and xanthine-based comfort system	Direct subject matter
Ketorolac ophthalmic	Active ingredient, salts, formulations, dosing	Separate active-ingredient estate
Diclofenac ophthalmic	Salt, solution, concentration, stability, use	Separate formulation and use estate
Flurbiprofen ophthalmic	Active ingredient and ophthalmic use	Overlaps only at broad NSAID-method concept level
Nepafenac ophthalmic	Prodrug, ocular conversion, suspension and dosing	Technically distinct
Bromfenac ophthalmic	Brominated NSAID, concentration, dosing, formulation	Technically distinct

The patent’s strongest historical feature was its specific combination of an ophthalmic NSAID and a xanthine derivative. Its commercial weakness today is that the entire patent term has ended and the covered suprofen product is not a major active U.S. market.

What manufacturing and intellectual-property barriers remain?

Patent 4,559,343 creates no current manufacturing barrier. A manufacturer could develop a suprofen ophthalmic solution without licensing the expired patent.

Remaining barriers may include:

API sourcing and quality control for suprofen.
Sterile ophthalmic manufacturing capability.
Preservative compatibility and container-closure integrity.
Ocular tolerability and stinging studies.
Stability of suprofen in the selected pH range.
FDA regulatory pathway for a discontinued or noncurrently marketed reference product.
Freedom-to-operate review of later patents covering delivery systems, packaging, preservative-free dosing, or new ophthalmic uses.
Commercial demand for a product competing against established ophthalmic NSAIDs.

The expired patent may still be cited during prosecution of later applications. Its disclosure could support novelty or obviousness challenges against claims directed to combining suprofen or another ophthalmic NSAID with caffeine or a related xanthine derivative.

What litigation and settlement issues affect the patent?

There is no current infringement litigation risk under Patent 4,559,343 because the patent expired more than two decades ago. The patent therefore cannot support:

A new Paragraph IV lawsuit;
A current 30-month approval stay;
A new preliminary injunction based on enforceable patent rights;
A royalty-bearing license required solely to practice its claims; or
A settlement restricting generic entry based solely on this patent.

Any historical litigation or settlement involving suprofen ophthalmic products would have no continuing exclusionary effect after expiration unless it included independent contractual restrictions or involved separate patents.

How strong is the patent estate for suprofen ophthalmic products?

The current U.S. patent estate is weak because Patent 4,559,343 is expired and no continuing exclusivity follows from it.

Historically, the patent had moderate claim breadth:

Claims 1 through 3 were narrower composition claims focused on suprofen.
Claim 4 was broader because it covered multiple listed NSAIDs and a structural xanthine genus.
Claims 6 and 7 returned to the commercially specific suprofen-caffeine combination.
The functional discomfort-reduction limitation could have created proof and claim-construction issues.
The preservative and buffer requirements narrowed claim 1.

From a modern freedom-to-operate perspective, the patent is low risk. From a patentability perspective, its disclosure remains relevant against new applications claiming ophthalmic NSAID formulations that use caffeine, theophylline, or theobromine to reduce ocular discomfort.

Key Takeaways

U.S. Patent 4,559,343 covers aqueous ophthalmic NSAID compositions and methods using low-level xanthine derivatives to reduce stinging.
The principal commercial embodiment is suprofen combined with caffeine.
Claims 1 through 3 focus on compositions; claims 4 through 7 focus on methods.
Claim 4 has the broadest technical scope because it covers multiple NSAIDs and a structural xanthine genus.
Claims 3 and 7 specify approximately 0.5% to 3.0% suprofen.
The patent issued December 17, 1985, and expired December 17, 2002.
It creates no current Paragraph IV, Orange Book, licensing, injunction, or generic-launch barrier.
Its principal continuing value is as prior art for ophthalmic NSAID comfort formulations.
A current product would require separate review of later patents, FDA pathway issues, sterile manufacturing, and commercial demand.

FAQs

Does Patent 4,559,343 cover caffeine-free suprofen eye drops?

No. The claims require a xanthine derivative. A caffeine-free formulation would not literally satisfy the xanthine limitation, although it could implicate other patents or prior-art issues.

Does the patent cover bromfenac or nepafenac?

Not expressly. The listed NSAID group in claim 4 does not identify bromfenac or nepafenac. Those products are governed by separate patent and regulatory histories.

Can a company license Patent 4,559,343 to launch suprofen ophthalmic drops?

A license is not required to practice an expired patent. Commercial agreements may still be negotiated for other assets, but this patent alone cannot impose a current royalty obligation.

Does the 0.05% xanthine limit apply to every claim?

No. The 0.05% limitation appears in the xanthine-related claim language, but claim scope must be assessed by claim dependency and construction. Claims 3 and 7 also contain the suprofen concentration range.

Could a new patent be obtained for a suprofen-caffeine ophthalmic formulation?

A new patent would need patentable subject matter distinct from the disclosure and claims of Patent 4,559,343. A routine reformulation of the same suprofen-caffeine concept would face substantial novelty and obviousness risk.

References

United States Patent and Trademark Office. (1985). Ophthalmic compositions containing a xanthine derivative and a nonsteroidal anti-inflammatory agent, U.S. Patent No. 4,559,343.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations, 44th ed. Center for Drug Evaluation and Research.
U.S. Food and Drug Administration. (n.d.). Orange Book: Approved drug products with therapeutic equivalence evaluations. Center for Drug Evaluation and Research.
United States Code. 35 U.S.C. § 154. Patent term and adjustment provisions.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	51522	⤷ Start Trial
Canada	1217144	⤷ Start Trial
Germany	3381396	⤷ Start Trial
European Patent Office	0105635	⤷ Start Trial
Japan	H0551568	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 4,559,343

Summary for Patent: 4,559,343