# US Patent 5,212,200: Scope, Claims, Expiration, and Ocular Prostaglandin Patent Landscape

US Patent 5,212,200 covers broad 13,14-dihydro-15-keto prostaglandin compounds used in topical ocular compositions and methods for treating ocular hypertension and glaucoma. The patent is associated with the unoprostone technology platform, including the isopropyl ester commonly known as unoprostone isopropyl or isopropyl unoprostone, formerly marketed in the United States as Rescula.

The patent issued on May 18, 1993. Because it was filed before the 1995 change to the United States patent-term regime, its ordinary term was generally 17 years from issuance. The patent therefore expired in May 2010, subject to any applicable patent-term adjustment or disclaimer. It no longer provides an enforceable United States patent barrier to generic development.

What technology does US Patent 5,212,200 protect?

The patent protects the use of a chemical genus of prostaglandin analogs as ocular hypotensive agents. Its central structural requirement is a 13,14-dihydro-15-keto prostaglandin having a substituted prostaglandin framework represented by formula I.

The claims cover:

Topical ophthalmic compositions.
Treatment of ocular hypertension.
Treatment of glaucoma.
Free carboxylic acids.
Physiologically acceptable salts.
A broad group of carboxylic acid esters.
Multiple prostaglandin ring systems, including the A, B, C, D and J series.
Compounds with an alkyl group at the C-20 position.
Compounds administered topically to the eye.
Alkyl ester forms of the terminal carboxyl group.

The claim strategy is expansive. Claim 1 covers the composition platform. Claims 2 and 3 cover therapeutic use. The remaining claims add structural, chemical-form, or route-of-administration limitations.

What is the relevance to unoprostone isopropyl?

Unoprostone isopropyl is a 13,14-dihydro-15-keto prostaglandin analog with an isopropyl ester at the terminal carboxyl group and an alkyl substitution at the C-20 position. Those features correspond directly to the limitations in claims 4, 5, 12, 13, 20 and 21.

The patent therefore appears designed to cover the active pharmaceutical ingredient and its ophthalmic use at a genus level, rather than only one commercial formulation. The commercial product Rescula used unoprostone isopropyl ophthalmic solution for reduction of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension [2].

How broad are the independent claims?

Claim 1: topical ocular composition

Claim 1 requires four principal elements:

A topical ocular composition.
An amount effective as an ocular hypotensive agent.
A 13,14-dihydro-15-keto prostaglandin within formula I, or an acceptable salt or listed ester.
A pharmaceutically acceptable carrier.

The claim is composition-focused. It does not require a particular concentration, preservative, tonicity agent, pH, viscosity modifier, container, or dosing schedule in the text provided.

The chemical scope is broad because the claim permits substantial variation in the Y and Z hydrocarbon chains:

Structural element	Claimed scope
Core	13,14-dihydro-15-keto prostaglandin
R group	Hydroxy, hydroxy C1-C3 alkyl, or C1-C2 alkyl
Y chain	Saturated or unsaturated C2-C6 hydrocarbon
Y substitution	Oxo, halogen, alkyl, or hydroxyl
Z group	C1-C10 saturated or unsaturated hydrocarbon
Z structure	Straight-chain, branched-chain, or ring
Z substitution	Halogen, alkyl, alkoxy, hydroxyl, phenyl, or phenoxy
Acid derivatives	Physiologically acceptable salts and specified esters
Carrier	Pharmaceutically acceptable carrier

The formula images supplied with the claim text define the exact A-group and stereochemical framework. That structural drawing is essential in a litigation-level claim construction because the text alone does not reproduce every bond, ring, stereocenter, or double-bond position.

Claims 2 and 3: method-of-use protection

Claim 2 covers administering an effective amount of the claimed prostaglandin to treat ocular hypertension. Claim 3 covers treatment of glaucoma.

These claims are broader than a claim limited to a specific product label. They are directed to therapeutic use and do not expressly require topical administration until dependent claim 11, or the corresponding dependent claim associated with claim 3.

The method claims require:

A human patient.
A condition requiring treatment.
Administration of the covered prostaglandin.
An amount effective to treat ocular hypertension or glaucoma.

Claims 2 and 3 could raise divided-infringement and induced-infringement issues if a manufacturer supplies a product with labeling directed to the claimed indication. Those issues are no longer commercially material for US Patent 5,212,200 because the patent has expired.

What do the dependent claims add?

The dependent claims divide the genus into chemical and therapeutic subgroups.

Claims	Added limitation	Commercial significance
4 and 12	Terminal alpha-chain carboxyl group is an alkyl ester	Covers ester prodrugs such as isopropyl ester forms
5 and 13	Alkyl group at C-20	Captures 20-alkyl prostaglandin analogs
6, 14 and 22	A-series prostaglandin	Narrows ring-system class
7, 15 and 23	B-series prostaglandin	Narrows ring-system class
8, 16 and 24	C-series prostaglandin	Narrows ring-system class
9, 17 and 25	D-series prostaglandin	Narrows ring-system class
10, 18 and 26	J-series prostaglandin	Narrows ring-system class
11 and corresponding route claim	Topical administration to the eye	Aligns the method with ophthalmic commercial use
20	Alkyl ester in the composition	Composition counterpart to claim 4
21	C-20 alkyl compound in the composition	Composition counterpart to claim 5

The supplied claim text contains apparent drafting errors. Claim 19 refers to “claims 4 or 12-19,” which appears to include the claim itself. Claims 18 and 19 also create an overlapping dependency structure. These errors would ordinarily be assessed against the issued patent document, prosecution history, and any certificate of correction.

Which commercial active ingredient is most closely associated with the patent?

The closest commercial association is unoprostone isopropyl.

Item	Description
Active ingredient	Unoprostone isopropyl
Drug class	Prostaglandin analog
Ophthalmic use	Reduction of elevated intraocular pressure
Product	Rescula ophthalmic solution
Former US sponsor	Novartis Pharmaceuticals Corporation
FDA pathway	New Drug Application
US approval	1994
US marketing status	Discontinued
Patent 5,212,200 status	Expired

Unoprostone differs pharmacologically from the prostaglandin F2-alpha receptor agonists latanoprost, travoprost and tafluprost. Unoprostone is generally described as a prostaglandin analog with a different pharmacologic profile and lower commercial penetration than the leading prostaglandin analog products [2, 3].

When did US Patent 5,212,200 lose exclusivity?

US Patent 5,212,200 issued on May 18, 1993. Its ordinary pre-Uruguay Round patent term was 17 years from issuance, placing the expected expiration in May 2010 [1].

Milestone	Date or status
Patent issue	May 18, 1993
Ordinary term basis	17 years from issue
Expected expiration	May 18, 2010
Current status	Expired
Current enforceability	No enforceable exclusionary rights under this patent

The patent cannot presently block an abbreviated new drug application, formulation development, manufacturing, importation, or sale on the basis of its expired claims.

The expiration analysis should be separated from regulatory exclusivity. Patent expiration does not itself establish that an ANDA product is approved. It removes the patent barrier but does not eliminate requirements relating to pharmaceutical equivalence, bioequivalence, chemistry, manufacturing and controls, labeling, or FDA approval.

What was the FDA status of Rescula and unoprostone isopropyl?

Rescula was approved for lowering elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension. The product was later discontinued in the United States. FDA records distinguish commercial discontinuation from withdrawal for safety or efficacy reasons [2].

The practical regulatory position is:

Rescula is not a currently marketed US product.
The original approval does not create a current commercial franchise.
The expired patent does not prevent a new sponsor from pursuing unoprostone isopropyl.
A new applicant would need to establish the applicable regulatory pathway based on the current reference-product and FDA listing status.
An ANDA strategy may be unavailable or commercially difficult if there is no eligible reference-listed drug or if the relevant listed drug status has changed.
A 505(b)(2) application could be considered where the applicant relies in part on FDA findings for a listed drug but proposes a different clinical, formulation, or labeling position.

The Orange Book must be reviewed for current listing status, therapeutic-equivalence evaluations and any patents still associated with a listed product [4]. An expired patent is not a continuing Orange Book barrier.

What is the Orange Book status of the patent?

US Patent 5,212,200 is not a current patent barrier. Any historical Orange Book listing associated with Rescula or unoprostone isopropyl has no remaining blocking effect after expiration.

The key distinction is between:

Patent listing: whether FDA historically listed the patent against an approved drug.
Patent enforceability: whether the patent remains legally enforceable.
Regulatory exclusivity: whether FDA granted a period preventing approval of certain competing applications.
Product marketing: whether the reference product is currently sold.

For a modern competitor, the relevant review would include FDA Orange Book data, discontinued-drug records, FDA patent-listing history and any current reference-product designation. The existence of US Patent 5,212,200 alone does not create a present Paragraph IV exposure.

Are there Paragraph IV challenges to US Patent 5,212,200?

No current Paragraph IV challenge can be commercially operative against an expired patent. Paragraph IV certifications are relevant when an ANDA applicant challenges a listed patent that has not expired. Once the patent term ends, the applicant generally relies on an expired-patent certification or otherwise treats the patent as nonblocking.

Historical litigation or an earlier Paragraph IV filing would not revive the patent or extend its term. A settlement agreement could affect launch timing only during the patent’s enforceable life and cannot extend the patent beyond its statutory expiration without separate legal authority.

The available claim set does not establish that a particular generic manufacturer filed a Paragraph IV certification against this patent. A company-specific litigation conclusion cannot be inferred from the claims alone.

What other patents covered competing ocular prostaglandins?

US Patent 5,212,200 belongs to an earlier generation of ocular prostaglandin patenting. Later commercial products were protected by separate composition, formulation, therapeutic-use and manufacturing patents.

Product	Active ingredient	Representative US patent	Patent focus	Commercial position
Rescula	Unoprostone isopropyl	US 5,212,200	Broad 13,14-dihydro-15-keto prostaglandin ocular-use genus	Discontinued in US
Xalatan	Latanoprost	US 5,296,504	Prostaglandin analog and ophthalmic use	Generic competition established
Lumigan	Bimatoprost	US 5,352,708	Bimatoprost composition and use	Generic competition established
Travatan	Travoprost	US 5,889,052	Travoprost and ocular hypotensive use	Generic competition established
Zioptan	Tafluprost	US 7,273,946	Tafluprost ophthalmic therapy	Patent estate historically later-expiring
Vyzulta	Latanoprostene bunod	Later formulation and method patents	Nitric-oxide donating prostaglandin analog	Separate, later estate

These patents are not statutory continuations of US 5,212,200 merely because they cover prostaglandin analogs. They should be analyzed separately for priority, terminal disclaimers, patent-term adjustment, Orange Book listing and claim overlap.

How does the patent estate compare with latanoprost, bimatoprost and travoprost?

US Patent 5,212,200 has broader chemical-genus language than a typical patent limited to one named active ingredient. That breadth increases potential blocking value during the patent term but also creates vulnerability to written-description, enablement, anticipation and obviousness challenges.

Factor	US 5,212,200	Typical later product patent
Claim type	Genus composition and method claims	Often species, formulation or use claims
Covered compounds	Broad prostaglandin analog class	Frequently one commercial molecule
Formulation specificity	Low in the claims provided	Often higher in later patents
Method-of-use scope	Ocular hypertension and glaucoma	May include dosing, concentration or patient subgroup
Litigation value during term	Potentially broad	Depends on species and product coverage
Current blocking value	None; expired	Depends on each patent’s expiration

Latanoprost, bimatoprost and travoprost generated larger commercial patent estates because each product supported multiple filings involving the active ingredient, formulations, salts, dosing regimens, manufacturing processes and regulatory exclusivities. US Patent 5,212,200 is more important historically as a platform patent than as a current barrier.

How strong are the claims under a validity analysis?

Claim breadth

The independent claims cover a large number of possible structures through flexible definitions for R, Y and Z. The inclusion of multiple prostaglandin series and numerous ester types expands the claim perimeter.

Written-description and enablement exposure

A genus claim covering many hydrocarbon substitutions, ring structures, heteroatom-free chains and ester forms may face written-description and enablement scrutiny if the specification does not disclose representative species across the full breadth. The patent’s strength would depend on the examples, synthetic methods, biological data and guidance provided for each subgenus.

Anticipation and obviousness exposure

Earlier prostaglandin patents and publications may disclose:

13,14-dihydro prostaglandins.
15-keto prostaglandins.
Prostaglandin ester prodrugs.
Ocular administration of prostaglandin analogs.
Ocular hypotensive effects of related compounds.

A validity analysis would compare the exact combination of structural limitations and ocular activity against each reference. A reference disclosing only systemic prostaglandin activity would not necessarily anticipate the ocular-use claims, but could be relevant to obviousness.

Claim-construction issues

Important construction questions include:

The meaning of “13,14-dihydro-15-keto-prostaglandin.”
Whether the formula requires a specific stereochemical configuration.
The boundaries of “hydrocarbon chain.”
Whether “forming a ring” includes monocyclic and fused structures.
The scope of “physiologically acceptable salts.”
The meaning of “carboxylic acid esters” in relation to the listed ester classes.
Whether the effective-amount limitation is a meaningful structural or only functional limitation.
Whether “topical ocular composition” requires administration to the ocular surface or merely suitability for such use.

Because the patent has expired, these questions have no present injunctive consequence but remain relevant to historical freedom-to-operate opinions, licensing audits and patent landscaping.

What formulation patents may still matter for an unoprostone product?

The expired genus patent does not exhaust the possible intellectual-property risks. A new unoprostone product could encounter later patents directed to:

Preservative-free ophthalmic solutions.
Specific pH and osmolality ranges.
Surfactant or solubilizer systems.
Container-closure systems.
Multidose ophthalmic dispensers.
Improved chemical stability.
Reduced irritation.
Particular dosing concentrations.
Combination therapy with beta blockers, carbonic anhydrase inhibitors or alpha agonists.
Manufacturing and purification processes.
Crystalline forms or impurity-control methods.

Those later rights would need a separate family-level search. They cannot be determined from US Patent 5,212,200 or the claims supplied.

What generic launch risks exist for unoprostone isopropyl?

The historical patent risk is low because US Patent 5,212,200 expired in 2010. The main current risks are regulatory and commercial.

Regulatory risks

A prospective sponsor must address:

Whether a current reference-listed drug exists.
Whether the product can use an ANDA pathway.
Whether a 505(b)(2) application is required.
Whether FDA considers the discontinued product suitable for generic reference purposes.
Whether clinical bridging or additional efficacy data are required.
Whether the proposed formulation is pharmaceutically equivalent.
Whether the inactive ingredients are acceptable for ophthalmic use.

Manufacturing risks

Unoprostone isopropyl may require control of:

Prostaglandin stereochemistry.
Double-bond geometry.
15-keto and 13,14-dihydro purity.
Ester hydrolysis.
Oxidation and degradation products.
Low-dose uniformity.
Sterility and particulate matter.
Container-closure compatibility.

These issues can increase development cost even where no blocking patent remains.

Commercial risks

The United States market for a reintroduced unoprostone product would face established generic prostaglandin therapies, including generic latanoprost, bimatoprost and travoprost. A sponsor would need a differentiated clinical, tolerability, dosing or payer proposition. The prior discontinuation of Rescula also creates demand-forecast and channel-access risk.

What licensing and settlement issues are associated with the patent?

The claims alone do not establish a license, assignment history, royalty agreement or patent-litigation settlement. The historical commercial development of unoprostone involved corporate transactions and product rights associated with the originator and later marketing partners, but a definitive analysis of license scope requires executed agreements and assignment records.

No settlement agreement should be presumed from the existence of the patent or from the former Rescula product. Any analysis of launch dates, royalty obligations or covenants would need to rely on public court filings, SEC disclosures, FDA submissions or recorded assignment documents.

What is the geographic coverage of US Patent 5,212,200?

US Patent 5,212,200 provides protection only in the United States. Corresponding foreign applications may have been filed in Japan, Europe and other jurisdictions, but foreign patent rights are independent.

A global freedom-to-operate review would need to separate:

United States composition claims.
European national or European Patent Convention claims.
Japanese composition and ophthalmic-use patents.
Product patents in major commercial markets.
Supplementary protection certificates.
Patent-term extensions.
Local regulatory exclusivities.
Manufacturing-site and importation risks.

Expiration in the United States does not establish expiration in any other jurisdiction.

Key Takeaways

US Patent 5,212,200 covers a broad genus of 13,14-dihydro-15-keto prostaglandins for ocular hypotension and glaucoma.
The claims include topical ophthalmic compositions, therapeutic methods, alkyl esters, C-20 alkyl compounds and A-, B-, C-, D- and J-series prostaglandins.
Unoprostone isopropyl is the commercial compound most closely associated with the patent.
The patent issued on May 18, 1993 and ordinarily expired on May 18, 2010.
The patent is no longer an enforceable US barrier to generic or follow-on development.
No current Paragraph IV risk can arise from an expired patent.
Later formulation, manufacturing, dosing and regulatory patents must be analyzed separately.
The principal current barriers to an unoprostone product are FDA pathway, reference-product status, manufacturing control and commercial demand.
The claims contain apparent dependency and typographical defects that would have required review against the issued patent and prosecution history.

FAQs

Can a generic manufacturer launch unoprostone isopropyl without licensing US Patent 5,212,200?

Yes. The patent’s ordinary term ended in 2010, so the patent no longer requires a license for US manufacture, sale or use.

Does the patent cover latanoprost, bimatoprost or travoprost?

The genus language may overlap structurally with related prostaglandin analogs, but those products were protected and regulated through separate patent estates. Product-specific coverage requires comparison with the exact formula and prosecution history.

Can an expired ocular-use patent support an FDA Paragraph IV lawsuit?

No. An expired patent cannot support a current infringement action based on an ANDA Paragraph IV certification.

Is unoprostone isopropyl eligible for an ANDA?

The answer depends on whether FDA recognizes an appropriate reference-listed drug and whether the proposed product meets ANDA requirements. Discontinued reference-product status can make a 505(b)(2) route more practical than an ANDA.

Could a later formulation patent block a new unoprostone product?

Yes. Expiration of US Patent 5,212,200 does not eliminate later patents covering specific formulations, delivery systems, manufacturing processes, dosing regimens or combination therapies.

References

United States Patent and Trademark Office. (1993). US Patent No. 5,212,200, Ocular hypotensive prostaglandins. U.S. Department of Commerce.
U.S. Food and Drug Administration. (1994). Rescula (unoprostone isopropyl ophthalmic solution) prescribing information. FDA.
American Academy of Ophthalmology. (2023). Primary open-angle glaucoma preferred practice pattern. American Academy of Ophthalmology.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book. FDA.
United States Patent and Trademark Office. (1996). US Patent No. 5,296,504, Ophthalmic solution containing latanoprost. U.S. Department of Commerce.
United States Patent and Trademark Office. (1997). US Patent No. 5,352,708, Ocular hypotensive agent. U.S. Department of Commerce.
United States Patent and Trademark Office. (1999). US Patent No. 5,889,052, Ophthalmic compositions containing travoprost. U.S. Department of Commerce.

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Japan	62-235890	Sep 18, 1987
Japan	62-334037	Dec 29, 1987

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	0289349	⤷ Start Trial	300135	Netherlands	⤷ Start Trial
European Patent Office	0289349	⤷ Start Trial	SPC/GB04/007	United Kingdom	⤷ Start Trial
European Patent Office	0289349	⤷ Start Trial	C300135	Netherlands	⤷ Start Trial
Austria	108330	⤷ Start Trial
Austria	111736	⤷ Start Trial
Austria	162074	⤷ Start Trial
Austria	72235	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 5,212,200

Summary for Patent: 5,212,200