United States Drug Patent 5,441,958: Claim Scope, Emedastine Exclusivity, and Patent Landscape

US Patent 5,441,958 protected the ophthalmic use of emedastine, specifically 1-(2-ethoxyethyl)-2-(4-methyl-1-homopiperazinyl)-benzimidazole and its ophthalmically acceptable acid-addition salts, for treating allergic conjunctivitis. The commercial product associated with the patent was Emadine, an emedastine difumarate ophthalmic solution.

The patent covered a method of treatment rather than the underlying chemical compound, a general ophthalmic composition, or a manufacturing process. Its term has expired. The patent therefore no longer blocks generic development, ophthalmic reformulation, or commercial use of emedastine in the United States.

What drug and product did US Patent 5,441,958 protect?

The patent relates to emedastine, an H1-antihistamine used in ophthalmic treatment of allergic conjunctivitis. The marketed ophthalmic product was emedastine difumarate ophthalmic solution, generally supplied at a concentration of 0.05% w/v.

Item	Details
Patent	US 5,441,958
Active ingredient	Emedastine
Protected salt	Emedastine difumarate, among other ophthalmically acceptable acid-addition salts
Therapeutic area	Allergic conjunctivitis
Route	Topical ocular administration
Commercial product	Emadine
Commercial sponsor	Alcon Laboratories, Inc.
FDA dosage form	Ophthalmic solution
Typical marketed strength	0.05%
Patent type	Method-of-treatment patent
Patent status	Expired
Statutory expiration	August 15, 2012, based on the 17-year term from the August 15, 1995 issue date

The patent claims do not cover all antihistamines, all allergic-eye treatments, or all emedastine products without a corresponding allergic-conjunctivitis treatment use. Infringement would have depended on practicing the claimed method with the specified compound or salt.

What does claim 1 of US 5,441,958 cover?

Claim 1 is the principal method claim. It requires four core elements:

A method for treating allergic conjunctivitis.
Topical administration.
Administration to an affected eye.
An antihistaminic effective amount of emedastine or an ophthalmically acceptable acid-addition salt.

The chemical limitation is narrow. It identifies the specific benzimidazole derivative:

1-(2-ethoxyethyl)-2-(4-methyl-1-homopiperazinyl)-benzimidazole.

The claim also covers ophthalmically acceptable acid-addition salts of that compound. Claim 5 expressly identifies the difumarate salt, which is the salt used in Emadine.

Claim 1 limitations

Claim element	Scope
Disease	Allergic conjunctivitis
Administration site	An affected eye
Route	Topical ocular administration
Pharmacologic effect	Antihistaminic effect
Active compound	Emedastine
Salt coverage	Ophthalmically acceptable acid-addition salts
Dose limitation	None stated in claim 1
Concentration limitation	None stated in claim 1
Formulation limitation	None stated in claim 1

The absence of a concentration limitation in claim 1 is significant. A product could fall within the literal scope of claim 1 at concentrations outside the ranges in claims 2 through 4, provided the other elements were met. Claims 2 through 4 narrow the method by adding concentration ranges, but they do not replace claim 1.

What formulations and concentrations are protected?

Claims 2 through 4 cover concentration ranges for the active compound. They do not claim a complete formulation containing a particular preservative, buffer, surfactant, viscosity agent, tonicity agent, or pH.

Claim	Concentration limitation
Claim 2	About 0.0001% to about 1.0% by weight
Claim 3	About 0.005% to about 0.2% by weight
Claim 4	About 0.05% to about 0.2% by weight

The ranges are nested:

Claim 4 is narrower than claim 3.
Claim 3 is narrower than claim 2.
Claim 2 is narrower than claim 1 because it adds a concentration requirement.
Claim 1 remains broader because it has no stated concentration range.

The marketed 0.05% product falls at the lower boundary of claim 4 and within claims 2 and 3. A 0.05% emedastine ophthalmic product used to treat allergic conjunctivitis would historically have presented the clearest infringement exposure under claim 4, assuming the product used the claimed compound or salt and the other claim elements were satisfied.

The patent does not, on its face, claim:

A specific preservative system.
A particular bottle or container.
A multidose delivery device.
A pH range.
An isotonicity range.
A viscosity range.
A particular dosing schedule.
A specific frequency of administration.
A combination with another ophthalmic drug.
A manufacturing process for emedastine difumarate.
A composition claim that applies independently of treatment use.

What does claim 5 protect?

Claim 5 depends on claim 1 and specifies the difumarate salt of emedastine.

Its practical scope is:

Treatment of allergic conjunctivitis;
By topical ocular administration;
Using an antihistaminic effective amount;
Of emedastine difumarate.

Claim 5 is narrower than claim 1 because it excludes other ophthalmically acceptable acid-addition salts. It is also narrower than claim 1 because it specifically requires the difumarate salt.

Claim 5 maps directly to the active pharmaceutical form used in Emadine. It was therefore commercially important even though it covered a narrower salt form than the parent claim.

When did US Patent 5,441,958 lose exclusivity?

The patent issued on August 15, 1995. Because the application predates the modern 20-year-from-earliest-effective-filing-date regime created by the Uruguay Round Agreements Act, its ordinary term was 17 years from issuance.

Event	Date
Patent issue	August 15, 1995
Ordinary patent term	17 years from issue
Expiration	August 15, 2012
Post-expiration status	No enforceable patent exclusivity under this patent

The expiration date is material because the patent’s claims are method claims. Once the patent expired, the claimed use of emedastine and emedastine difumarate for allergic conjunctivitis ceased to be an enforceable US patent barrier.

FDA regulatory exclusivity is separate from patent exclusivity. Any Hatch-Waxman exclusivity associated with the original product would have expired well before the patent’s expiration date. FDA approval of Emadine did not extend the patent term.

What was the Orange Book status of emedastine?

Emadine was listed as an FDA-approved ophthalmic solution containing emedastine difumarate. The Orange Book is the relevant FDA source for approved drug products, patent listings, and regulatory exclusivity information.

US Patent 5,441,958 was historically relevant to the Orange Book position for Emadine because it claimed the allergic-conjunctivitis treatment use associated with the approved product. Its listing did not create a composition-of-matter monopoly over every emedastine product.

The patent’s expiration removed the principal patent-based Orange Book barrier associated with the claimed use. The FDA Orange Book does not convert an expired patent into an active exclusivity right.

Were Paragraph IV challenges relevant?

A Paragraph IV certification would have been relevant only while an unexpired listed patent blocked approval of a competing ANDA. Under the Hatch-Waxman framework, an ANDA applicant could certify that a listed patent was invalid, unenforceable, or would not be infringed.

For US 5,441,958, the practical timeline was:

Period	Paragraph IV significance
Before patent expiration	A Paragraph IV certification could trigger patent litigation
During a timely infringement action	FDA approval could be subject to the statutory 30-month stay
After August 15, 2012	The patent could no longer support a patent-based approval block
Current commercial relevance	No live Paragraph IV barrier from this patent

A generic applicant could also have used a Paragraph III certification before expiration and deferred approval until the patent expired. After expiration, the patent no longer required that strategy.

No current Paragraph IV litigation can preserve exclusivity after the patent term has ended. A patent challenge filed after expiration would generally have little commercial value because the challenged claims are no longer enforceable.

How strong was the patent estate for emedastine?

The historical estate was narrow but commercially aligned with the approved product.

Strengths

The patent had several favorable characteristics:

It identified the specific active compound used in the marketed ophthalmic product.
It covered the therapeutic indication associated with the product.
It covered topical administration to an affected eye.
It expressly addressed ophthalmically acceptable acid-addition salts.
Dependent claims covered the commercial concentration range.
Claim 5 specifically addressed emedastine difumarate.

Limitations

The patent also had important limitations:

It did not claim the basic chemical compound as a composition of matter.
It did not claim a proprietary formulation architecture.
It did not claim a device or container system.
It did not claim manufacturing or crystallization technology.
It did not provide post-expiration protection.
It depended on a method-of-use theory requiring treatment of allergic conjunctivitis.
The concentration claims did not independently cover a formulation without the claimed treatment use.

From a historical enforcement perspective, the patent was more relevant to a product labeled for allergic conjunctivitis than to an unlabeled or differently labeled emedastine product. Method-of-use enforcement can also depend on the product label, prescribing behavior, promotional conduct, and evidence that the accused product is intended for the claimed use.

From a current perspective, its legal strength is zero because the patent has expired.

What generic entry risks existed?

Before expiration, a competing emedastine ophthalmic product faced several potential risks:

Literal method infringement. A product using emedastine difumarate at 0.05% and labeled for allergic conjunctivitis would have closely matched claims 1, 2, 3, 4, and 5.
Induced infringement. A sponsor could face exposure if its labeling or promotion encouraged physicians or patients to practice the claimed treatment method.
FDA listing risk. An ANDA applicant would have had to address the listed patent through the applicable certification.
Regulatory timing risk. A Paragraph IV filing could have triggered litigation and a 30-month stay.
Labeling constraints. A carve-out from the patented indication might have been considered, although the commercial value of an emedastine ophthalmic product would depend heavily on treatment of allergic conjunctivitis.

After August 15, 2012, these patent-specific risks ended. Remaining barriers would have been regulatory, commercial, manufacturing, quality, supply-chain, or formulation related rather than based on US 5,441,958.

Which companies challenged or licensed the patent?

The patent record and standard FDA drug-patent materials identify the patent as linked to the Emadine product and its sponsor. No continuing US exclusivity, active patent litigation, or current licensing restriction is created by US 5,441,958.

A patent license would have been commercially relevant before expiration if a third party wanted to market emedastine for the claimed use. After expiration, a license is not required to practice the expired claims. Private settlement or supply agreements could still affect a transaction, but they would be separate from patent enforceability.

The patent itself does not establish a continuing license obligation for generic manufacturers, contract manufacturers, or later ophthalmic sponsors.

How does emedastine compare with competing allergy eye drugs?

Emedastine competed with several antihistamine or dual-action ophthalmic products, including olopatadine, ketotifen, azelastine, bepotastine, and alcaftadine.

Product class	Example active ingredient	Patent landscape relative to US 5,441,958
Emedastine ophthalmic	Emedastine difumarate	The cited method patent is expired
Olopatadine ophthalmic	Olopatadine hydrochloride	Separate compound, formulation, and method patents
Ketotifen ophthalmic	Ketotifen fumarate	Separate compound and formulation estate
Azelastine ophthalmic	Azelastine hydrochloride	Separate chemical and formulation estate
Bepotastine ophthalmic	Bepotastine besilate	Separate later-generation estate
Alcaftadine ophthalmic	Alcaftadine	Separate later-generation estate

These products cannot be treated as alternatives within the scope of US 5,441,958 merely because they treat the same disease. The patent claims emedastine, not the broader therapeutic category of topical antihistamines.

What geographic coverage did the patent provide?

US 5,441,958 provided rights in the United States only. A US patent does not create rights in Canada, Europe, Japan, China, or other jurisdictions.

Foreign counterpart patents, if any, would have required separate prosecution and would have had separate expiration dates, claim scopes, and legal statuses. The US expiration date does not automatically determine the status of any foreign family member.

For US commercial planning, the relevant conclusion is direct: the cited patent no longer creates a US exclusionary right.

What manufacturing or intellectual-property barriers remain?

US 5,441,958 does not create a current manufacturing barrier. It does not claim:

Emedastine synthesis.
Emedastine difumarate crystallization.
A specific polymorph.
A sterile manufacturing process.
A preservative system.
A container-closure system.
A formulation pH.
A particular ophthalmic delivery device.

A current entrant would instead face ordinary pharmaceutical development requirements, including API sourcing, impurity controls, sterile ophthalmic manufacturing, container-closure qualification, stability testing, bioequivalence or other FDA requirements, and commercial differentiation.

Those requirements are operational barriers, not continuing patent exclusivity under US 5,441,958.

Key Takeaways

US 5,441,958 is a method-of-treatment patent for topical emedastine therapy for allergic conjunctivitis.
Claim 1 covers emedastine and ophthalmically acceptable acid-addition salts without a concentration limitation.
Claims 2 through 4 cover nested concentration ranges from about 0.0001% to about 1.0%, with claim 4 covering about 0.05% to about 0.2%.
Claim 5 specifically covers emedastine difumarate.
The commercial 0.05% Emadine product aligned closely with the dependent concentration and salt claims.
The patent expired on August 15, 2012.
No current Paragraph IV, Orange Book, settlement, or litigation issue can preserve exclusivity under this expired patent.
The patent did not claim a composition, formulation platform, device, or manufacturing process.
There is no biosimilar issue because emedastine is a synthetic small molecule, not a biologic.
Current entry barriers are regulatory, manufacturing, quality, supply, and commercial rather than patent-based.

Frequently Asked Questions

Is emedastine difumarate still protected by US 5,441,958?

No. The patent expired on August 15, 2012. Its claims are no longer enforceable in the United States.

Does US 5,441,958 cover all ophthalmic antihistamines?

No. It covers a specific emedastine compound and its ophthalmically acceptable acid-addition salts when used topically to treat allergic conjunctivitis.

Does the patent cover an emedastine formulation without an allergic-conjunctivitis indication?

The claims are method claims. A formulation used for a purpose outside the claimed treatment method would not automatically fall within the literal claim language.

Is there a biosimilar pathway for Emadine?

No. Emedastine is a synthetic small-molecule drug. A competing product would generally proceed through an ANDA or another small-molecule FDA pathway, not the biosimilar pathway.

Can a company launch a 0.05% emedastine ophthalmic product in the United States?

The expired patent does not block that launch. The sponsor would still need to satisfy FDA approval, manufacturing, quality, labeling, and commercial requirements.

References

United States Patent and Trademark Office. (1995). U.S. Patent No. 5,441,958. https://patents.google.com/patent/US5441958
U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations: Orange Book. https://www.accessdata.fda.gov/scripts/cder/ob/
U.S. Food and Drug Administration. (1997). Emadine (emedastine difumarate ophthalmic solution) prescribing information. https://www.accessdata.fda.gov/drugsatfda/
U.S. Food and Drug Administration. (n.d.). Hatch-Waxman amendments and abbreviated new drug applications. https://www.fda.gov/drugs/types-applications/abbreviated-new-drug-application-anda
DailyMed. (n.d.). Emadine: Emedastine difumarate ophthalmic solution. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Japan	4-329216	Dec 09, 1992

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	185696	⤷ Start Trial
Australia	5744294	⤷ Start Trial
Australia	667613	⤷ Start Trial
Canada	2151385	⤷ Start Trial
Germany	69326840	⤷ Start Trial
Denmark	0673250	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 5,441,958

Summary for Patent: 5,441,958