US Drug Patent 5,001,153: Claim Scope, Unoprostone Protection, Expiration, and Patent Landscape

US Patent No. 5,001,153 protected topical ocular hypotensive compositions containing unoprostone isopropyl ester, also known as 13,14-dihydro-15-keto-20-ethyl-PGF2α isopropyl ester or UF-021. The patent covered the composition, its glaucoma-treatment concentration, and its formulation as topical eye drops. It did not claim the compound itself, a manufacturing process, a dosing regimen, or a method-of-treatment claim in independent form.

The patent issued in 1991 and reached the end of its pre-URAA 17-year term in 2008. It therefore does not create a current US patent barrier to generic or follow-on development. The commercial product associated with the compound was Rescula, an ophthalmic solution approved by the FDA for lowering elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension [1, 2].

What drug and product did US Patent 5,001,153 protect?

US 5,001,153 covered unoprostone isopropyl ester, a prostaglandin-related ocular hypotensive agent. The compound is structurally distinct from latanoprost, travoprost, bimatoprost, and tafluprost, although all belong to the broader prostaglandin or prostamide glaucoma-drug field.

Item	Data
US patent	5,001,153
Patent title	Ocular hypotensive compositions
Active compound	13,14-dihydro-15-keto-20-ethyl-PGF2α isopropyl ester
Common name	Unoprostone isopropyl ester
Development code	UF-021
Product	Rescula ophthalmic solution
Therapeutic class	Ocular hypotensive agent
Dosage form	Topical ophthalmic solution or eye drop
Original developer	Fujisawa Pharmaceutical Co., Ltd.
US approval	1997
FDA pathway	NDA approval
Patent term status	Expired
Approximate patent expiration	2008

Unoprostone was developed as a topical treatment for elevated intraocular pressure. The approved Rescula product contained unoprostone isopropyl ester in an ophthalmic solution administered as eye drops [1].

What are the claims of US Patent 5,001,153?

The three claims form a nested composition claim structure.

Claim 1: Broad composition claim

Claim 1 covers:

A topical ocular hypotensive composition comprising an amount of 13,14-dihydro-15-keto-20-ethyl-PGF2α isopropyl ester effective as an ocular hypotensive agent and a pharmaceutically acceptable carrier.

The claim has four principal limitations:

The product must be a composition.
The composition must be topical and intended for ocular use.
It must contain unoprostone isopropyl ester.
It must contain a pharmaceutically acceptable carrier.

The active ingredient must be present in an amount effective as an ocular hypotensive agent. This is a functional limitation. The claim does not specify a single concentration, pH, preservative, buffer, tonicity agent, viscosity modifier, or dosing frequency.

The carrier limitation is broad. It can encompass aqueous ophthalmic vehicles and conventional excipients used in sterile eye drops, provided the carrier is pharmaceutically acceptable and the composition remains suitable for topical ocular administration.

Claim 2: Glaucoma-treatment limitation

Claim 2 narrows claim 1 by requiring the amount of active ingredient to be effective for treating glaucoma.

The supplied claim text refers to "13,14-dihydro-15-keto-20-ethyl-PGE2α isopropyl ester." Claim 1 refers to the PGF2α compound. That inconsistency appears to be a transcription or typographical error because the patented active ingredient and the commercial product are associated with the PGF2α derivative, unoprostone isopropyl ester. Read as a dependent claim, claim 2 incorporates the compound identified in claim 1 and adds the glaucoma-treatment limitation.

Claim 2 is narrower than claim 1 in intended therapeutic use, but it remains a composition claim. It does not independently claim administering the composition to a patient.

Claim 3: Eye-drop formulation

Claim 3 narrows claim 1 to a topical eye-drop form.

This limitation is commercially important because it maps directly onto the dosage form used for Rescula. It does not, however, require a particular container, drop volume, preservative system, concentration, or administration schedule.

How broad is the patent scope?

The patent scope was commercially meaningful but technically narrow compared with a compound patent.

Claim feature	Claim 1	Claim 2	Claim 3
Unoprostone isopropyl ester required	Yes	Yes	Yes
Topical ocular composition required	Yes	Yes	Yes
Pharmaceutically acceptable carrier required	Yes	Yes	Yes
Effective ocular hypotensive amount required	Yes	Yes	Yes
Glaucoma treatment limitation	No	Yes	No
Eye-drop limitation	No	No	Yes
Specific concentration required	No	No	No
Specific excipients required	No	No	No
Manufacturing process claimed	No	No	No
Composition of matter claim	No	No	No
Stand-alone method-of-treatment claim	No	No	No

A product could fall within claim 1 even if it used a different carrier, preservative, buffer, or packaging configuration. A formulation design that substituted a different inactive ingredient would not automatically avoid infringement if the resulting product still contained the claimed active compound in a topical ocular composition with a pharmaceutically acceptable carrier.

The claim would not reach:

A product containing a different prostaglandin analog;
An oral, injectable, or non-ocular formulation;
A topical product containing unoprostone but lacking a pharmaceutically acceptable carrier;
A formulation in which the active ingredient was not present at an effective ocular hypotensive amount;
A manufacturing process that did not itself make or use the claimed composition.

What formulations are protected by US 5,001,153?

The patent protects the active ingredient in a topical ophthalmic composition rather than a particular formulation recipe.

Potentially covered formulations include:

Sterile aqueous eye drops;
Buffered ophthalmic solutions;
Preserved multi-dose eye-drop products;
Single-dose preservative-free products;
Formulations with conventional ophthalmic tonicity agents;
Formulations with viscosity-enhancing excipients;
Other topical ocular vehicles containing the claimed active compound.

The patent does not expressly require the formulation to reproduce the Rescula label composition. A generic formulation could therefore implicate the patent based on the active ingredient and route even if its inactive ingredients differed.

Because the patent has expired, formulation differences now have greater relevance to regulatory equivalence, product performance, stability, preservative tolerability, and freedom to operate under later patents than to US 5,001,153 itself.

Did US 5,001,153 claim a method of treating glaucoma?

No independent method-of-treatment claim is identified in the supplied claims. Claim 2 refers to an amount effective for treating glaucoma, but that language describes the composition's functional purpose. It does not expressly claim the act of administering the composition to a patient.

This distinction matters in patent analysis:

A composition claim generally focuses on the product.
A method claim focuses on the steps of treatment.
A formulation claim focuses on the physical and chemical arrangement of the dosage form.
A use limitation can narrow a composition claim without converting it into a method claim.

The patent's protection therefore centered on the unoprostone ophthalmic composition and its eye-drop embodiment.

When did US 5,001,153 lose exclusivity?

The patent expired in approximately 2008 under the pre-URAA patent-term rule applicable to the patent. The patent issued before the modern 20-year-from-earliest-effective-filing-date regime took effect. Its term was therefore generally calculated as 17 years from issuance, subject to any patent-term adjustment or disclaimer shown in the official patent record [3].

The relevant exclusivity timeline is:

Event	Date or period
Patent issuance	1991
Rescula US approval	1997
Five-year NCE exclusivity, if applicable	Expired by approximately 2002
Patent expiration	Approximately 2008
Current patent enforceability	None

The patent's expiration removed the principal patent-based barrier created by US 5,001,153. Any current product strategy must be assessed against later patents, regulatory requirements, trade secrets, trademarks, and product-specific formulation or manufacturing rights rather than this patent.

What was the Orange Book status of US 5,001,153?

US 5,001,153 was associated with the Rescula NDA and was historically relevant to the FDA Orange Book patent listing for the product [2]. The Orange Book listing would have provided notice of the patent identified by the NDA holder in connection with the approved drug.

For an ANDA applicant, a listed patent could have required one of the following certifications:

Paragraph I, if no patent information had been submitted;
Paragraph II, if the patent had expired;
Paragraph III, if the applicant accepted approval after patent expiration;
Paragraph IV, if the applicant alleged that the patent was invalid or would not be infringed.

Once the patent expired, a Paragraph II or Paragraph III pathway would generally be more relevant than a Paragraph IV challenge to this patent. A Paragraph IV certification against an expired patent would have little practical value unless tied to an earlier filing date or another legal issue.

Were there Paragraph IV challenges or generic launch disputes?

The supplied patent information does not establish a specific Paragraph IV litigation event against US 5,001,153. The patent's early expiration date also reduces the commercial significance of a later Paragraph IV case.

For an unoprostone generic, the main historical questions would have been:

Whether US 5,001,153 was still listed and unexpired when the ANDA was filed;
Whether the applicant certified to the patent under Paragraph II, III, or IV;
Whether other patents were listed for the Rescula NDA;
Whether FDA approval was blocked by regulatory exclusivity;
Whether the applicant could demonstrate pharmaceutical equivalence and bioequivalence for the ophthalmic solution.

Unoprostone is a small molecule, not a biologic. A follow-on product would therefore proceed through the abbreviated new drug application system rather than the biosimilar pathway under section 351(k) of the Public Health Service Act.

What is the current biosimilar and generic risk?

Biosimilar risk is not applicable. Unoprostone isopropyl ester is a synthetic small molecule, and a follow-on product would be a generic ophthalmic drug rather than a biosimilar.

Generic entry risk under US 5,001,153 is high because:

The patent has expired;
The claims do not cover a continuing manufacturing monopoly;
The claims do not cover a broad class of prostaglandin analogs;
The claims do not create current exclusivity for unoprostone;
The active ingredient and dosage form are defined in a way that can be evaluated under the ANDA framework.

The practical barriers are regulatory and commercial. These include sourcing the active pharmaceutical ingredient, establishing sterile manufacturing controls, demonstrating product quality, addressing ophthalmic equivalence, and determining whether a market remains after the branded product's commercial withdrawal or limited availability.

How does the patent compare with competing glaucoma-drug patents?

US 5,001,153 was narrower than patents that claimed a compound of matter or a broad chemical genus. It protected a specific active ingredient in a specific therapeutic composition.

Product	Active ingredient	Typical patent strategy	Relation to US 5,001,153
Rescula	Unoprostone isopropyl ester	Topical ocular composition	Directly associated
Xalatan	Latanoprost	Compound, composition, formulation, and use patents	Different active ingredient
Travatan	Travoprost	Compound and ophthalmic formulation patents	Different active ingredient
Lumigan	Bimatoprost	Compound and formulation patents	Different active ingredient
Zioptan	Tafluprost	Compound and formulation patents	Different active ingredient

The competing products do not fall within claim 1 merely because they are prostaglandin-related ocular hypotensives. Claim 1 requires the specific unoprostone isopropyl ester molecule. A competitor using latanoprost, travoprost, bimatoprost, or tafluprost would not infringe based solely on the supplied claims.

How strong was the patent estate for unoprostone?

The patent estate reflected in US 5,001,153 was moderate for the commercial formulation and weak for long-term lifecycle protection.

Strengths

It identified the active ingredient with chemical specificity.
It covered the commercially relevant topical ocular route.
It covered the eye-drop dosage form.
Its broad carrier language reduced opportunities to avoid the claim through routine excipient changes.
Claim 2 linked the composition to glaucoma treatment.

Limitations

It did not claim the active compound as a composition of matter.
It did not claim a manufacturing process.
It did not claim a specific concentration or release profile.
It did not claim a device or container.
It did not provide a current enforceable right after 2008.
It did not cover competing prostaglandin analogs.

The patent was therefore effective as an early product-composition patent but offered limited lifecycle control after expiration.

What manufacturing and geographic barriers remain?

US 5,001,153 provides no current US manufacturing exclusion. The patent's geographic scope was limited to the United States. Foreign protection would have depended on separately filed national or regional patent rights, not automatically on the US patent.

Potential non-patent barriers include:

Stereochemically controlled synthesis of unoprostone;
Control of prostaglandin-related impurities;
Sterile ophthalmic manufacturing;
Stability of the active ingredient in solution;
Container-closure compatibility;
Preservative performance;
FDA facility and quality-system requirements;
Access to qualified API suppliers;
Commercial scale and expected market demand.

These barriers can delay generic entry without restoring patent exclusivity. They are operational and regulatory constraints, not rights arising from US 5,001,153.

What patent litigation and settlement issues affect the asset?

No active US litigation can be inferred from the patent's expired status. Any historical litigation or settlement involving Rescula would need to be evaluated separately from the patent's claim scope.

The patent's expiration also eliminates the principal basis for a current exclusionary settlement. A settlement signed after expiration would generally require a different legal or commercial basis, such as supply, distribution, regulatory, or trademark arrangements. The supplied patent data do not identify a settlement agreement, reverse-payment arrangement, or continuing license connected to US 5,001,153.

Key Takeaways

US 5,001,153 covered topical ocular compositions containing unoprostone isopropyl ester.
The claims focused on a specific active compound, a pharmaceutically acceptable carrier, ocular hypotensive activity, glaucoma treatment, and eye-drop presentation.
The patent did not claim the compound itself, a manufacturing process, or a stand-alone treatment method.
Claim 2 contains a PGF2α/PGE2α inconsistency in the supplied text; the patented commercial compound is the PGF2α derivative unoprostone isopropyl ester.
The patent issued in 1991 and expired in approximately 2008.
It is not a current US barrier to generic unoprostone development.
Biosimilar analysis is inapplicable because unoprostone is a synthetic small molecule.
Competing glaucoma drugs using latanoprost, travoprost, bimatoprost, or tafluprost are outside the supplied claims because they use different active ingredients.
Current commercial risk depends on regulatory feasibility, API sourcing, sterile manufacturing, later patent rights, and market demand rather than US 5,001,153.

FAQs

Is US Patent 5,001,153 still enforceable?

No. The patent expired under the pre-URAA patent-term framework, with expiration occurring approximately 17 years after its 1991 issuance.

Does US 5,001,153 cover latanoprost?

No. The claims require unoprostone isopropyl ester. Latanoprost is a different prostaglandin analog.

Could a generic unoprostone eye drop avoid claim 3 by changing the bottle?

Changing the bottle would not, by itself, avoid claim 3 if the product remained an eye drop containing unoprostone isopropyl ester in a topical ophthalmic composition.

Is unoprostone eligible for an ANDA or a biosimilar application?

Unoprostone is a synthetic small molecule. A follow-on product would generally use the ANDA pathway, not the biosimilar pathway.

Did the patent protect a specific Rescula concentration?

The supplied claims do not require a specific concentration. They require an amount effective as an ocular hypotensive agent, while the approved product's concentration and formulation are established through the FDA product labeling.

References

U.S. Food and Drug Administration. (1997). Rescula (unoprostone isopropyl ophthalmic solution) prescribing information. FDA.
U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations: Orange Book. FDA. https://www.accessdata.fda.gov/scripts/cder/ob/
United States Patent and Trademark Office. (1991). Ocular hypotensive compositions, U.S. Patent No. 5,001,153. https://patents.google.com/patent/US5001153A/en
U.S. Food and Drug Administration. (n.d.). Drugs@FDA: FDA-approved drugs. FDA. https://www.accessdata.fda.gov/scripts/cder/daf/

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
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 5,001,153

Summary for Patent: 5,001,153