U.S. Patent 4,871,865: Olopatadine Scope, Claims, Expiration and Patent Landscape

U.S. Patent 4,871,865 is the foundational U.S. compound patent for olopatadine, an antihistamine and mast-cell stabilizer used in ophthalmic products including Patanol, Pataday and Pazeo. Its claims cover the olopatadine chemical entity and pharmaceutically acceptable salts, including olopatadine hydrochloride. The patent issued in 1989 under the pre-URAA patent term rules and is expired. It no longer blocks generic olopatadine development, although later formulation and method-of-use patents may have affected specific products.

What compound does U.S. Patent 4,871,865 protect?

The patent protects a dibenzoxepin derivative identified in dependent claim 3 as:

(Z)-11-(3-(dimethylamino)propylidene)-6,11-dihydrodibenz[b,e]oxepin-2-acrylic acid.

This structure is commonly identified as olopatadine, although commercial products generally contain olopatadine hydrochloride rather than the free-acid form.

The patent’s claim architecture is:

Claim	Scope	Practical subject matter
1	Genus claim	A defined dibenzoxepin derivative or a pharmacologically and pharmaceutically acceptable salt
2	Subgenus claim	The compound in which R2 and R3 are methyl
3	Species claim	The Z-isomer corresponding to olopatadine

The central commercial significance is that claim 1 reaches the active pharmaceutical ingredient and its acceptable salts, while claims 2 and 3 narrow the scope to the dimethylamino side chain and the named Z-isomer.

How broad is claim 1 of U.S. Patent 4,871,865?

Claim 1 is a structurally limited Markush claim rather than an unrestricted claim to all dibenzoxepin derivatives.

Its principal limitations are:

R1 is fixed as -CH2-O-;
R2 and R3 may independently be hydrogen or C1-C4 alkyl;
R4 is a C1-C2 bivalent hydrocarbon group;
R4 is attached to the aromatic ring system at the 2-position;
n is fixed at 2;
the compound may be present as a pharmaceutically acceptable salt.

The claim therefore covers a family of substituted dibenzoxepin compounds with a basic aminoalkylidene substituent and a short carbon linker attached at the 2-position.

The following substitutions are within the literal language of claim 1, subject to the complete chemical formula appearing in the issued patent:

Variable	Permitted groups
R1	-CH2-O-
R2	Hydrogen or C1-C4 alkyl
R3	Hydrogen or C1-C4 alkyl
R4	C1-C2 bivalent hydrocarbon group
n	2

The claim does not broadly cover every antihistamine, every dibenzoxepin, or every olopatadine analog. A compound lacking the specified -CH2-O- relationship, using a longer linker, placing the side chain at another ring position, or having a different ring system would generally fall outside the literal scope of claim 1.

What does claim 2 add?

Claim 2 limits claim 1 by requiring both R2 and R3 to be methyl groups.

This limitation corresponds to the dimethylamino side chain in olopatadine. Claim 2 eliminates claim 1 embodiments in which either amino substituent is hydrogen or another C1-C4 alkyl group.

Claim 2 is narrower than claim 1 but remains broader than claim 3 because it does not, on its face, identify every stereochemical and positional feature of the specific olopatadine molecule unless those features are inherited from the claim 1 formula.

What does claim 3 cover?

Claim 3 identifies the commercial active ingredient by name and stereochemical configuration. It covers the Z-isomer of the named dibenzoxepin acrylic-acid compound.

The Z configuration is commercially important. Olopatadine is not merely a generic dibenzoxepin derivative; the claimed geometry of the exocyclic double bond forms part of the compound’s identity.

The claim text supplied uses the expression “acrylic acid.” Commercial chemical references commonly describe olopatadine as a dibenzoxepin-2-acetic-acid derivative. For infringement and validity analysis, the issued patent, certified patent file and chemical structure control over secondary nomenclature or OCR-transcribed text.

What salts are protected by U.S. Patent 4,871,865?

Claim 1 expressly covers a “pharmacologically and pharmaceutically acceptable salt” of the claimed compound.

That language is significant because commercial ophthalmic products use olopatadine hydrochloride. The salt limitation supports coverage of the hydrochloride salt even though claim 3 names the acid form.

The salt language does not automatically cover:

Any salt of an unrelated olopatadine analog;
A formulation in which olopatadine is chemically transformed;
A covalent prodrug;
A different active ingredient with similar pharmacology;
A polymorph unless the polymorph is otherwise covered by the claimed compound or a later patent.

The patent is principally a composition-of-matter patent. It is not a detailed patent on ophthalmic vehicles, preservatives, viscosity modifiers, packaging or dosing regimens.

When did U.S. Patent 4,871,865 expire?

U.S. Patent 4,871,865 issued on October 3, 1989. Because it was governed by the pre-URAA patent term rules, its ordinary term was 17 years from issuance.

Event	Date
Patent issue	October 3, 1989
Ordinary 17-year expiration	October 3, 2006
Potential six-month pediatric exclusivity period	Up to April 3, 2007

The patent is expired. Any pediatric exclusivity associated with an FDA product would have been a regulatory exclusivity period and would not revive the patent.

There is no current composition-of-matter patent barrier based on U.S. Patent 4,871,865.

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

Olopatadine ophthalmic products received FDA approval through drug applications for allergic conjunctivitis and related ocular indications. Key U.S. products included:

Product	Active ingredient	Typical strength	FDA status
Patanol	Olopatadine hydrochloride	0.1%	Approved prescription ophthalmic solution
Pataday	Olopatadine hydrochloride	0.2%, later 0.7%	Approved ophthalmic products; some strengths moved to OTC status
Pazeo	Olopatadine hydrochloride	0.7%	Approved prescription ophthalmic solution

The Orange Book historically associated olopatadine products with patent and exclusivity information. The original compound patent has expired and should be distinguished from later patents listed for particular formulations, strengths, dosing schedules or products.

Orange Book listing does not itself establish that every claim in a listed patent is valid or infringed. It identifies patents submitted by the NDA holder for the approved product under the Hatch-Waxman framework.

What later patents protected olopatadine formulations?

After expiration of the compound patent, commercial protection shifted toward product-specific formulations and delivery characteristics.

Potential later patent categories included:

Higher-concentration ophthalmic solutions;
Reduced dosing-frequency formulations;
Preservative systems;
Improved ocular residence time;
Stabilized aqueous compositions;
Formulations using specific pH or tonicity ranges;
Methods for treating allergic conjunctivitis with particular concentrations;
Product-specific dosing regimens.

These patents generally have narrower scope than claim 1 of U.S. Patent 4,871,865. They may cover a particular formulation even though they do not prevent manufacture of olopatadine as an active pharmaceutical ingredient.

A generic developer can therefore face separate questions:

Is olopatadine itself unpatented?
Is the proposed salt or solid form covered?
Is the proposed ophthalmic composition covered?
Is the proposed concentration covered?
Is the proposed dosing schedule covered?
Does the proposed label induce infringement of a method-of-use claim?

Were Paragraph IV challenges relevant to olopatadine?

Yes. After the compound patent expired, generic applicants could pursue approval for olopatadine ophthalmic solutions through the ANDA pathway without confronting the original composition patent as an active barrier.

For patents listed against a particular NDA, a generic applicant could use:

Paragraph I certification if no patent information was listed;
Paragraph II certification if the patent had expired;
Paragraph III certification if approval was deferred until expiration;
Paragraph IV certification if the listed patent was invalid, unenforceable or not infringed.

The commercial importance of a Paragraph IV challenge depended on whether a later formulation or method patent remained listed and whether the generic proposed product fell within its claims. The 30-month stay under 21 U.S.C. § 355(j)(5)(B)(iii) applied only where the statutory conditions were met, including timely patent litigation by the NDA holder.

The original compound patent does not create a current Paragraph IV obstacle because it is expired.

Which companies commercialized or challenged olopatadine products?

The commercial chain involved several companies over time:

Kyowa Hakko entities were associated with development and patenting of olopatadine.
Alcon commercialized major ophthalmic products in the United States.
Novartis became involved through its ownership of Alcon.
Generic manufacturers entered with olopatadine hydrochloride ophthalmic solutions after the relevant exclusivity barriers ended.
Multiple manufacturers have marketed prescription and, for eligible products, OTC olopatadine products.

The competitive field includes branded Patanol, Pataday and Pazeo products, authorized generics, prescription generic solutions and OTC allergy products.

What generic entry risks remain?

The core active ingredient risk is low because the composition patent has expired.

Residual risks are product-specific:

Risk area	Assessment
Olopatadine molecule	Low patent risk from U.S. 4,871,865
Olopatadine hydrochloride	Covered by the expired salt-inclusive composition claim
0.1% ophthalmic solution	Generic competition established; later formulation patents require review
0.2% and 0.7% products	Greater need to review concentration and formulation patents
Dosing regimen	Potential method-of-use risk if a later patent remains enforceable
Preservative system	Possible formulation claim risk
OTC labeling	Regulatory and labeling constraints remain separate from composition patents
Manufacturing process	Process patents may create independent risk if a specific process is used

A generic product does not necessarily infringe a formulation patent merely because it contains olopatadine. Infringement depends on all claim limitations, including excipients, concentration, pH, preservative content, packaging and use instructions.

How strong is the patent estate for olopatadine?

The estate has two distinct phases.

Foundational estate

The foundational estate was strong when U.S. Patent 4,871,865 was enforceable because it covered the active compound and pharmaceutically acceptable salts. A competing product containing olopatadine hydrochloride could not avoid the patent by selecting the salt form.

That protection is now historical. The patent’s claim breadth no longer provides blocking exclusivity.

Follow-on estate

The later estate is narrower and product dependent. Its strength turns on:

Whether a patent is still unexpired;
Whether the patent is listed for the relevant NDA;
Whether the generic formulation practices every claim limitation;
Whether the claim is directed to a composition or merely a method;
Whether the patent has survived validity challenges;
Whether an authorized generic or settlement agreement limits commercial entry.

The strongest remaining barriers, where applicable, are generally formulation and dosage claims rather than claims to olopatadine itself.

What geographic coverage did the patent have?

U.S. Patent 4,871,865 provided protection only in the United States. Corresponding foreign applications may have protected olopatadine in other jurisdictions, but expiration dates and enforceability depended on each country’s filing, grant, supplementary protection and pediatric-extension rules.

For global launch planning, the U.S. patent should be analyzed separately from:

European Patent Office family members;
Japanese patents;
Canadian patents;
Australian patents;
National patents in major ophthalmic markets.

The U.S. expiration date does not establish freedom to operate in Europe, Japan or other jurisdictions.

What licensing and settlement issues affected olopatadine?

Publicly visible commercial rights were connected to the relationship among Kyowa Hakko, Alcon and later Novartis. The original patent’s value was primarily tied to product commercialization and supply of the active ingredient.

Any settlement involving a generic applicant would need to be reviewed at the individual litigation and product level. A settlement could address:

An agreed generic launch date;
Authorized-generic supply;
Restrictions on formulation or labeling;
Patent dismissals;
Covenant-not-to-sue terms;
Allocation of later-listed formulation patents.

The expiration of U.S. Patent 4,871,865 does not resolve separate settlement obligations involving later patents.

Key Takeaways

U.S. Patent 4,871,865 is the foundational olopatadine compound patent.
Claim 1 covers a defined dibenzoxepin genus and pharmaceutically acceptable salts.
Claim 2 narrows the invention to the dimethylamino substituent.
Claim 3 specifically identifies the Z-isomer corresponding to olopatadine.
The patent covered olopatadine hydrochloride through its salt language.
The patent issued in 1989 and its ordinary U.S. term expired in 2006.
Any pediatric exclusivity could have extended market protection only into 2007.
The patent is no longer a current U.S. barrier to generic olopatadine.
Remaining patent risk lies mainly in later formulations, dosing regimens, concentrations and product-specific methods of use.
A complete freedom-to-operate analysis must separate the expired compound patent from later Orange Book-listed formulation patents.

FAQs

Does U.S. Patent 4,871,865 cover olopatadine hydrochloride?

Yes. Claim 1 covers pharmaceutically acceptable salts of the claimed compound, which includes the hydrochloride salt used in commercial olopatadine ophthalmic products.

Can a company manufacture generic olopatadine after expiration of the patent?

Yes, subject to FDA approval and any unexpired patents covering the proposed formulation, dosage regimen, manufacturing process or labeling.

Does the patent cover Patanol and Pataday formulations?

It covers the olopatadine active ingredient in those products, but it does not necessarily cover every excipient combination, concentration or delivery system used in the commercial formulations.

Is olopatadine a biologic subject to biosimilar competition?

No. Olopatadine is a chemically synthesized small-molecule drug. Competition proceeds through generic-drug pathways, principally ANDAs, rather than the biosimilar pathway under the Public Health Service Act.

What is the main litigation risk for a new olopatadine ophthalmic product?

The main risk is not U.S. Patent 4,871,865. It is potential infringement of later patents directed to a specific concentration, formulation, preservative system, dosing schedule, manufacturing process or method of treating ocular allergy.

References

United States Patent and Trademark Office. (1989). U.S. Patent No. 4,871,865: Dibenzoxepin derivatives, processes for preparation thereof and pharmaceutical compositions containing same. U.S. Department of Commerce.
U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations. FDA.
U.S. Food and Drug Administration. (1996). Patanol (olopatadine hydrochloride ophthalmic solution) prescribing information. FDA.
U.S. Food and Drug Administration. (2008). Pataday (olopatadine hydrochloride ophthalmic solution) prescribing information. FDA.
U.S. Food and Drug Administration. (2015). Pazeo (olopatadine hydrochloride ophthalmic solution) prescribing information. FDA.
Hatch, H. R. (1984). Drug Price Competition and Patent Term Restoration Act, Pub. L. No. 98-417, 98 Stat. 1585.

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
United Kingdom	8520662	Aug 17, 1985

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	125535	⤷ Start Trial
Austria	51867	⤷ Start Trial
Austria	97401	⤷ Start Trial
Germany	3650357	⤷ Start Trial
Germany	3670290	⤷ Start Trial
Germany	3689311	⤷ Start Trial
European Patent Office	0214779	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 4,871,865

Summary for Patent: 4,871,865