United States Patent 5,631,287: Claim Scope, Expiration, and Prostaglandin Ophthalmic Patent Landscape

United States Patent No. 5,631,287 covers methods for improving the chemical stability of aqueous prostaglandin compositions by adding polyethoxylated castor oil. The claims are directed primarily to formulation use, not to the underlying prostaglandin molecules or to a particular finished product. The patent issued May 20, 1997, and its pre-1995 filing date placed it under the former 17-year patent term. It therefore expired May 20, 2014, absent an unusual terminal-disclaimer or term adjustment issue. The patent creates no current U.S. exclusivity barrier.

The commercial relevance of the patent was greatest for aqueous ophthalmic prostaglandin formulations, particularly compositions containing travoprost, latanoprost-related compounds, or other prostaglandin analogs at low concentrations. Because the claims are expired, a current formulation developer does not require a license from this patent.

What does U.S. Patent 5,631,287 protect?

The patent protects a formulation-stabilization method with four principal technical elements:

An aqueous composition.
A therapeutically effective amount of a prostaglandin.
Addition of a chemically stabilizing amount of polyethoxylated castor oil.
Improved chemical stability of the composition.

Independent claim 1 is the controlling claim. The remaining claims narrow the scope by specifying the castor-oil concentration, the castor-oil type, the prostaglandin identity, the prostaglandin concentration, and the ophthalmic route.

The patent does not broadly claim every stable prostaglandin formulation. It requires the use of polyethoxylated castor oil as the stabilizing agent. A formulation stabilized solely by polysorbate, a cyclodextrin, a buffer, an antioxidant, a chelating agent, or a different nonionic surfactant would not fall within the literal language of claim 1 unless the formulation also used the claimed castor-oil material.

Claim construction summary

Claim	Principal limitation	Practical effect
1	Aqueous prostaglandin composition stabilized with polyethoxylated castor oil	Broadest method claim
2	Castor oil concentration of about 0.02 wt% to about 20.0 wt%	Concentration range
3	About 0.1 wt% to about 5.0 wt%	Narrower concentration range
4	About 0.5 wt% to about 2.0 wt%	Narrowest concentration range
5	PEG-2 to PEG-200 castor oils or PEG-5 to PEG-200 hydrogenated castor oils	Defines material genus
6	PEG-15 to PEG-50 castor oils	Intermediate material genus
7	PEG-30 to PEG-35 castor oils	Narrow material genus
8	Enumerated prostaglandins, including latanoprost, cloprostenol isopropyl ester, PGF2alpha isopropyl ester and fluprostenol isopropyl ester	Defines covered active ingredients
9	Seven compounds selected from claim 8	Narrower chemical group
10	Two specified chlorinated cyclohexyl prostaglandin esters	Narrowest listed active-ingredient group
11	Prostaglandin concentration of about 0.0001 wt% to about 0.1 wt%	Covers low-dose formulations
12	Topically administrable ophthalmic composition	Limits claim 1 to topical ophthalmic use

The claims use "about," which normally gives a reasonable measurement tolerance rather than an unlimited range. The prosecution history would be relevant to determine how the Patent Office treated those ranges, but the issued claim language establishes the principal boundaries.

How broad is claim 1?

Claim 1 is technically broad but legally dependent on a specific mechanism and excipient.

The claim does not limit the prostaglandin to the compounds listed in claim 8. Any therapeutically effective prostaglandin could potentially satisfy claim 1 if the other elements are met. Claims 8 through 10 narrow the active ingredient to specified chemical structures.

The claim also does not specify:

A particular pH.
A particular buffer.
A particular container.
A particular preservative.
A particular dosage strength.
A particular shelf-life period.
A particular manufacturing process.
A particular brand or indication.

The phrase "chemically-stabilizing amount" is a functional limitation. A claimant would generally need to establish that the amount of polyethoxylated castor oil actually improves chemical stability, such as by reducing degradation products or preserving prostaglandin assay during storage. The mere presence of the excipient may not be sufficient if the formulation does not achieve the claimed stabilizing function.

The claim is therefore broader than a claim limited to a specific commercial formulation, but narrower than a claim covering all stable aqueous prostaglandin products.

What formulations are protected by the patent?

The strongest historical coverage is for low-dose ophthalmic formulations containing a prostaglandin analog and a polyethoxylated castor-oil surfactant.

Claim 12 is important because ophthalmic prostaglandin products generally contain active ingredient at very low concentrations. Claim 11 expressly covers prostaglandin levels from approximately 0.0001 wt% to 0.1 wt%. That range encompasses many ophthalmic dosage strengths, although a product-by-product analysis would require the exact formulation composition.

The most commercially relevant castor-oil materials are likely to include:

Polyoxyl 35 castor oil.
Polyoxyl 30 castor oil.
Related PEG-30 to PEG-35 castor oils.
Selected hydrogenated castor oils, depending on the claim and formulation.

A product containing PEG-35 castor oil at a concentration between approximately 0.5 wt% and 2.0 wt% would fall within the literal scope of claims 4 and 7 if it also satisfied the aqueous, prostaglandin, ophthalmic and stability requirements.

The claims do not require the polyethoxylated castor oil to be the only stabilizer. A formulation could contain buffers, preservatives, tonicity agents, chelators, polymers or other surfactants and still potentially meet the claims.

Which prostaglandins are listed in claims 8 through 10?

Claim 8 includes a broad group of prostaglandin analogs and derivatives. The list includes:

Latanoprost, identified in the claim as PhXA41.
Cloprostenol isopropyl ester.
Fluprostenol isopropyl ester.
PGF2alpha isopropyl ester.
Multiple 9-chloro prostaglandin esters, amides and related derivatives.
Several cyclohexyl, cyclopentyl, adamantyl and aryl ester variants.
Compounds containing 3-oxa or 3-thia substitutions.
Compounds containing chlorophenoxy substituents.

Claim 9 narrows the list to seven specified compounds. Claim 10 narrows it further to two chlorinated cyclohexyl prostaglandin esters:

The isopropyl ester.
The tert-butyl ester.

The chemical nomenclature supplied in the issued claims contains apparent typographical errors, including "dLhydroxy," "cydohexyl," "ll-hydroxy," and inconsistent stereochemical formatting. For enforcement purposes, the relevant inquiry would be whether a court could identify the claimed compound with reasonable certainty from the patent specification, prosecution history and accepted chemical nomenclature.

Was Patent 5,631,287 an Orange Book patent?

Patent 5,631,287 is not best characterized as a currently operative Orange Book barrier.

The patent claims a method of stabilizing a composition with an excipient. It does not claim a specific approved drug substance in the manner typical of an active-ingredient patent, nor does it claim a finished dosage form with the full product composition. FDA Orange Book listing rules require patents to be submitted by the NDA holder when they claim the drug substance, drug product or an approved method of use, subject to FDA regulations and FDA's listing practices.[2]

A formulation patent can be Orange Book-listed if it claims an approved drug product. However, the presence of a patent in the historical patent landscape does not establish that it was listed for a particular NDA. The controlling records are the historical FDA Orange Book entries and the NDA holder's patent certifications.

The supplied claim set alone does not establish an Orange Book listing for any specific product. The patent's current status is unaffected by any former listing because the patent expired in 2014.

When did Patent 5,631,287 lose exclusivity?

Event	Date or status
Patent issued	May 20, 1997
Governing term	Generally 17 years from grant for the pre-June 8, 1995 application
Nominal expiration	May 20, 2014
Current status	Expired
Current blocking right	None in the United States
Paragraph IV relevance	Historical only
Current license requirement	None based solely on this patent

The patent was filed before the change to the 20-year-from-filing term. Under the transitional patent-term rules, patents issuing from qualifying pre-June 8, 1995 applications generally received a 17-year term from grant. The patent is therefore long expired under U.S. law.[1]

Expiration eliminates the right to exclude, but it does not erase the historical importance of the patent. It may remain relevant as prior art against later applications claiming the same stabilization concept, excipient class or prostaglandin formulation.

How does the patent compare with prostaglandin product patents?

Patent 5,631,287 is a formulation-stability patent. It should be separated from patents covering the prostaglandin active ingredient, analog synthesis, therapeutic use or specific commercial dosage form.

Patent category	Typical subject matter	Relationship to 5,631,287
Active-ingredient patent	Chemical structure of latanoprost, travoprost or another analog	Separate and potentially earlier barrier
Synthesis patent	Manufacturing route or intermediates	Separate manufacturing/IP barrier
Method-of-use patent	Treatment of glaucoma, ocular hypertension or another indication	Separate regulatory and litigation issue
Formulation patent	Specific excipients, pH, concentration, container or stability profile	Closest category
Device patent	Dropper, bottle, insert or delivery system	Separate patent family
Stability-method patent	Use of polyethoxylated castor oil to improve stability	Direct category of 5,631,287

For latanoprost, travoprost, bimatoprost and tafluprost, the principal historical barriers generally involved active-ingredient patents, product formulation patents, method-of-use patents, pediatric exclusivity and regulatory exclusivity. Patent 5,631,287 could have added formulation risk where the accused product used the specified castor-oil excipient, but it was not the sole determinant of generic entry.

What generic entry risks existed?

Before expiration, a generic or follow-on ophthalmic developer would have evaluated four infringement questions:

Does the product contain an aqueous composition?
Does it contain a therapeutically effective prostaglandin?
Does it contain PEG castor oil or PEG hydrogenated castor oil within a claimed category?
Is the excipient present in an amount that chemically stabilizes the prostaglandin?

A product using a different surfactant could have reduced literal infringement risk. A developer also could have challenged the claims based on anticipation, obviousness, written description, enablement, indefiniteness or lack of demonstrated stability effect. A Paragraph IV certification would have been relevant only if the patent had been listed for the relevant NDA and remained unexpired.

After May 20, 2014, these questions ceased to create a U.S. launch block. They remain relevant only to historical litigation, damages periods, patent-license audits or the interpretation of later patents.

Were there Paragraph IV challenges or settlements?

The supplied information does not establish a particular Paragraph IV certification, litigation case, settlement agreement or license involving Patent 5,631,287. Patent litigation cannot be inferred solely from the claim language or the patent number.

A complete historical assessment would distinguish among:

Patent 5,631,287 itself.
Related continuation and divisional applications.
Patents listed for latanoprost, travoprost or other prostaglandin products.
Paragraph IV cases filed against those listed patents.
Settlement agreements governing generic launch dates.
State-law or licensing disputes involving formulation technology.

Because the patent expired in 2014, any historical Paragraph IV dispute would now have no prospective exclusionary effect.

How strong was the patent estate?

The patent's historical strength was moderate for a narrow formulation design and limited for the broader prostaglandin market.

Strengths

Claim 1 covered a functional stability method rather than a single named compound.
Claims 2 through 7 provided multiple concentration and excipient fallbacks.
Claims 8 through 10 targeted specific prostaglandin analogs.
Claim 12 focused on commercially relevant topical ophthalmic use.
Low prostaglandin concentrations in claim 11 aligned with ophthalmic dosage forms.

Weaknesses

The claims depended on the presence of polyethoxylated castor oil.
The "chemically-stabilizing amount" limitation could require analytical proof.
The patent did not cover formulations using only other surfactants.
The listed active ingredients did not necessarily correspond to every commercial prostaglandin product.
The patent expired in 2014.
Later products could avoid the claims through different excipients or formulation strategies.

The patent was therefore more relevant as a formulation-specific layer of protection than as a platform patent covering all prostaglandin ophthalmics.

What manufacturing and geographic barriers remain?

There is no current U.S. manufacturing barrier created by Patent 5,631,287. The expired patent does not prevent manufacture, importation, sale or formulation development in the United States.

The patent's geographic scope was limited to the United States. Foreign counterparts, if any, would have required separate validity and expiration analysis. Expiration in the United States does not establish the status of corresponding patents in Europe, Japan, Canada, China or other jurisdictions.

Current barriers may instead arise from:

Active-ingredient patents in specific countries.
Manufacturing-process patents.
Drug-device patents.
Trade secrets concerning impurity control or formulation scale-up.
Regulatory requirements for ophthalmic sterility and container-closure integrity.
Product-specific patents listed in foreign or U.S. regulatory databases.

No such barrier can be attributed to U.S. Patent 5,631,287 after its expiration.

Key Takeaways

U.S. Patent 5,631,287 covers aqueous prostaglandin stabilization using polyethoxylated castor oil.
The broadest claim requires an aqueous composition, a therapeutically effective prostaglandin amount and a chemically stabilizing amount of the castor-oil excipient.
Claims 2 through 7 define concentration and PEG castor-oil subranges.
Claims 8 through 10 identify specific prostaglandin analogs, including latanoprost-related compounds, cloprostenol isopropyl ester and fluprostenol isopropyl ester.
Claim 12 narrows the invention to topical ophthalmic compositions.
The patent issued May 20, 1997, and nominally expired May 20, 2014.
It creates no current U.S. generic-launch or formulation-development barrier.
Any historical Orange Book, Paragraph IV, litigation or settlement relevance must be assessed against specific NDA and court records, not the patent claims alone.
Current competitive risk is more likely to arise from active-ingredient, method-of-use, device, manufacturing or later formulation patents.

Frequently Asked Questions

Does Patent 5,631,287 cover latanoprost?

Yes, claim 8 expressly lists latanoprost, identified as PhXA41. Coverage would also require the aqueous composition and polyethoxylated castor-oil stabilization limitations. The patent is expired.

Does using PEG-35 castor oil create infringement risk today?

No, not under Patent 5,631,287 in the United States. The patent expired in 2014. A separate later patent could still matter if it claims the same formulation or use.

Is Patent 5,631,287 a patent on travoprost?

No. The claims do not broadly claim travoprost as a chemical compound. They claim a stabilization method in which specified prostaglandins, including fluprostenol isopropyl ester, are used with polyethoxylated castor oil.

Can an expired patent remain relevant to a new patent application?

Yes. The expired patent can operate as prior art against later claims directed to the same or an obvious variation of the stabilization method, excipient combination or prostaglandin formulation.

Does the patent block biosimilar or generic ophthalmic development?

No. Prostaglandin ophthalmic products are generally small-molecule drug products, so the principal regulatory pathway is abbreviated new drug application review rather than biosimilar approval. This expired patent does not block either pathway.

References

United States Patent and Trademark Office. (2024). Patent term adjustment and patent term provisions. U.S. Department of Commerce.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations. Center for Drug Evaluation and Research.
U.S. Patent No. 5,631,287. (1997). Stable prostaglandin compositions. United States Patent and Trademark Office.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	208621	⤷ Start Trial
Australia	4649596	⤷ Start Trial
Australia	700574	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 5,631,287

Summary for Patent: 5,631,287