US Patent 5,849,792: Claim Scope, Expiration, Orange Book Status and Prostaglandin Patent Landscape

US Patent 5,849,792 protected aqueous ophthalmic prostaglandin compositions stabilized with polyethoxylated castor oil and an antimicrobial preservative. Its principal commercial relevance was to preserved prostaglandin eye-drop formulations, particularly formulations containing travoprost-related prostaglandins and other ocular hypotensive agents.

The patent is expired. Its composition and glaucoma-treatment claims no longer create a current US patent barrier to generic development. The patent remains relevant as prior art and as a historical reference for formulation strategy, Orange Book listing analysis, and the development of later travoprost and prostaglandin formulation patents.

What does US Patent 5,849,792 cover?

The patent claims an aqueous pharmaceutical composition containing four required elements:

A prostaglandin.
A polyethoxylated castor oil.
An antimicrobial preservative.
A pharmaceutically acceptable vehicle.

The polyethoxylated castor oil must be present in an amount "effective to enhance the chemical stability" of the prostaglandin. Claim 13 extends the composition concept to topical treatment of glaucoma or ocular hypertension.

The central inventive concept is formulation stabilization. Polyethoxylated castor oil is used as a solubilizing or surfactant component that also improves prostaglandin stability in an aqueous, preserved ophthalmic vehicle.

What formulation elements are required by independent claim 1?

Claim 1 is a combination claim. A product would need to satisfy every limitation to fall within its literal scope.

Claim element	Scope
Aqueous composition	The formulation must contain water or an aqueous vehicle
Prostaglandin	Broadly defined, subject to the patent specification and dependent-claim Markush groups
Polyethoxylated castor oil	Must be present in a stability-enhancing amount
Antimicrobial preservative	A preservative is mandatory
Pharmaceutically acceptable vehicle	The vehicle must be suitable for pharmaceutical use

The claim does not require an ophthalmic route, glaucoma indication, specific pH, a particular preservative, or a fixed prostaglandin concentration. Those limitations appear in dependent claims or are supplied by the specification.

The phrase "effective to enhance the chemical stability" is a functional limitation. It requires a technical showing that the selected castor-oil surfactant improves chemical stability relative to an appropriate comparator or otherwise performs the claimed stabilizing function. The claim does not define a single test method or numerical stability threshold.

How narrow are claims 2 through 7?

Claims 2 through 7 progressively limit the concentration and identity of the polyethoxylated castor oil.

Claim	Limitation
2	About 0.02 wt% to about 20.0 wt%
3	About 0.1 wt% to about 5.0 wt%
4	About 0.5 wt% to about 2.0 wt%
5	PEG-2 to PEG-200 castor oils and PEG-5 to PEG-200 hydrogenated castor oils
6	PEG-15 to PEG-50 castor oils
7	PEG-30 to PEG-35 castor oils

The claim hierarchy is commercially important. Claim 1 is broad but potentially more vulnerable to anticipation or obviousness arguments. Claims 4 and 7 are narrower and more closely aligned with practical ophthalmic formulations using mid-range PEG castor oils.

The concentration ranges overlap substantially. A formulation containing 1.0 wt% of PEG-35 castor oil would fall within claims 2, 3, 4, 5, 6 and 7 if the remaining claim elements were satisfied.

What is the likely commercial surfactant target?

The claim language points to PEG-30 to PEG-35 castor oils and hydrogenated castor oils used as ophthalmic solubilizers. Commercial excipients in this category include polyoxyl castor oil and polyoxyl hydrogenated castor oil materials, including products commonly identified by trade names such as Cremophor EL or Cremophor RH grades.

The patent does not require a particular trade-name excipient. A composition can fall within the claims based on the chemical identity and function of the excipient, even if the supplier or trade name differs.

Which prostaglandins are covered by claim 8?

Claim 8 contains a broad Markush group covering numerous prostaglandin analogues and esters. It expressly includes:

Latanoprost.
Cloprostenol isopropyl ester.
Fluprostenol isopropyl ester.
PGF2alpha isopropyl ester.
Multiple chlorinated, cyclohexyl-substituted and oxa-prostaglandin analogues.
Amide, dimethylamide, tert-butyl ester, isopropyl ester, cyclopentyl ester, adamantyl ester and aryl ester forms.
Several stereochemical variants.

The claim is not limited to approved products. It covers research compounds and potential drug candidates that satisfy the structural definitions in the Markush group.

Does claim 8 cover travoprost?

The inclusion of fluprostenol isopropyl ester is significant because travoprost is a fluprostenol derivative used in ophthalmic treatment. The patent's exact structural coverage must be assessed against the chemical identity and stereochemistry of the active ingredient, but the claim was drafted to reach a broad group of prostaglandin analogues relevant to ocular hypotension.

The commercial product connection is strongest where the active ingredient, surfactant, preservative and aqueous vehicle correspond to the claimed formulation combination. Merely using a prostaglandin listed in claim 8 does not establish infringement. The other elements of claim 1, including the stabilizing function of the polyethoxylated castor oil, are also required.

What additional limitations appear in claims 9 through 12?

Claims 9 and 10 narrow the prostaglandin group to a subset of chlorinated, cyclohexyl-substituted oxa-prostaglandin esters.

Claim 10 is the narrowest compound-selection claim. It covers the isopropyl ester and tert-butyl ester forms of the specified chlorinated prostaglandin analogue.

Claim 11 limits the prostaglandin concentration to about 0.0001 wt% to about 0.1 wt%. This range is consistent with low-dose ophthalmic prostaglandin formulations.

Claim 12 limits the composition to a topically administrable ophthalmic composition.

The claim structure creates several potential infringement paths:

A broad composition theory under claim 1.
A concentration-based theory under claims 2 through 4 and 11.
An excipient-identity theory under claims 5 through 7.
An active-ingredient theory under claims 8 through 10.
An ophthalmic-use theory under claim 12.

What does claim 13 cover?

Claim 13 is a method-of-treatment claim for glaucoma and ocular hypertension. It requires:

Topical administration to an affected eye.
An aqueous composition.
A prostaglandin.
A polyethoxylated castor oil.
An antimicrobial preservative.
An ophthalmically acceptable vehicle.
A stabilizing amount of the polyethoxylated castor oil.

Claim 13 is narrower than a general composition claim because it requires a therapeutic use and topical administration. It could historically have been relevant to product labeling, physician-directed use and induced-infringement theories. It does not cover every use of a claimed formulation because the glaucoma or ocular-hypertension treatment limitation must be satisfied.

When did US Patent 5,849,792 expire?

US Patent 5,849,792 was issued on December 15, 1998. Its effective nonprovisional filing date was in 1997, following an earlier priority filing. On the standard US patent-term calculation, the patent expired in 2017, approximately 20 years from the applicable nonprovisional filing date, subject to any patent-term adjustment or disclaimer reflected in the USPTO record.[1][2]

Event	Date or period
Earliest priority period	1996
US nonprovisional filing	1997
Patent issued	December 15, 1998
Standard 20-year term	2017
Current status	Expired

The expiration removes the patent's enforceable exclusionary right. It does not eliminate the patent's value as prior art or its relevance to prosecution history and freedom-to-operate analysis.

What is the Orange Book status of US Patent 5,849,792?

The patent is not a live Orange Book barrier today because it has expired. Any historical listing associated with a prostaglandin ophthalmic product would no longer block an ANDA based on an unexpired patent claim.

For current generic entry, the relevant Orange Book questions are:

Whether later, unexpired formulation patents remain listed.
Whether method-of-use patents remain listed for the proposed labeling.
Whether the reference product has remaining regulatory exclusivity.
Whether the applicant must certify under Paragraph IV to any unexpired listed patent.

FDA Orange Book listings identify patents submitted by sponsors for approved drug products. They do not independently determine claim validity, enforceability or infringement.[3]

What Paragraph IV challenges were relevant?

A Paragraph IV certification is relevant only to an unexpired patent listed for the reference product. Because US Patent 5,849,792 expired in 2017, a new ANDA applicant would not need to make a Paragraph IV certification to this patent.

Historically, an ANDA applicant could have challenged the patent by asserting that:

The proposed formulation did not contain polyethoxylated castor oil.
The selected excipient was not within the claimed PEG castor-oil categories.
The excipient was not present in an amount that enhanced chemical stability.
The active ingredient was outside the Markush group.
The product lacked an antimicrobial preservative.
The composition was not aqueous or ophthalmically acceptable.
The claims were invalid for anticipation, obviousness, lack of written description or lack of enablement.

The functional stability limitation would likely have been a central dispute. A challenger would need to analyze the specification, examples, comparator formulations and relevant prior art rather than rely solely on the ingredient list.

Which later patents created the more important travoprost barriers?

The commercial patent landscape for prostaglandin ophthalmic products extended beyond US Patent 5,849,792. Later patents could cover:

The specific active ingredient.
Salt, ester or stereochemical forms.
Preservative systems.
Surfactant combinations.
Buffer systems.
Low-dose formulations.
Container or delivery systems.
Preservative-free or reduced-preservative formulations.
Manufacturing and purification methods.

For travoprost products, later Alcon and Novartis patent families were more commercially significant after the expiration of the earlier broad stabilization patent. The exact barrier depended on the reference product, product version and Orange Book listing at the time of ANDA filing.

How does the patent compare with latanoprost formulation patents?

Issue	US 5,849,792	Latanoprost formulation estate
Active ingredient	Broad prostaglandin Markush group, including latanoprost	Primarily latanoprost-specific composition and use claims
Surfactant	Polyethoxylated castor oil	Product-specific excipient systems, often involving different surfactants
Preservative	Required	Varies by product and formulation
Indication	Glaucoma and ocular hypertension in claim 13	Glaucoma and ocular hypertension
Current status	Expired	Depends on the individual patent family
Generic pathway	No current barrier from this patent	ANDA certification depends on unexpired listed patents

The patent should not be treated as a complete patent estate for either latanoprost or travoprost. It is one formulation patent with broad historical coverage.

What patent claims remain relevant to formulation design?

Although the patent is expired, its claim architecture identifies the principal design-around variables:

Excipient design

A developer can avoid the literal castor-oil limitations by using a different solubilizer, such as a polysorbate, poloxamer, cyclodextrin, or another compatible nonionic surfactant. The alternative must still satisfy stability, solubility, tolerability and preservative requirements.

Preservative design

The claims require an antimicrobial preservative. A preservative-free product would avoid that express limitation, although separate patents may cover preservative-free packaging or formulation systems.

Concentration design

A formulation outside the claimed concentration ranges may avoid claims 2 through 4 and 11. It would not necessarily avoid claim 1, which has no numerical concentration limitation, if the castor oil still performs the claimed stability-enhancing function.

Active-ingredient design

Claims 8 through 10 can be avoided by selecting an active ingredient outside the listed Markush groups. This approach is less relevant for a generic seeking to reproduce the reference product but can be important for new-product development.

Vehicle and dosage form

The patent is directed to aqueous compositions. Non-aqueous, emulsion, suspension, gel or depot systems may raise different claim issues. A different dosage form does not automatically avoid infringement if the final product contains an aqueous phase and satisfies the claim language.

How strong was the patent estate?

The estate was historically broad at the formulation level but is now commercially weak because the patent has expired.

Strength factor	Assessment
Breadth of claim 1	Broad combination claim
Active-ingredient coverage	Broad Markush group
Excipient specificity	Moderate to strong for PEG castor oils
Stability limitation	Potentially fact-intensive
Ophthalmic relevance	Strong through claims 12 and 13
Current enforceability	None after expiration
Prior-art value	Material
Generic-entry significance today	None for this patent alone

The most valuable historical claims were likely claims 4, 7, 11 and 12, which align the excipient, concentration and dosage form with practical ophthalmic formulations. Claim 13 added treatment-use coverage but required proof that the marketed formulation and use satisfied every listed limitation.

What litigation or settlement agreements affected the patent?

US Patent 5,849,792 is expired and does not create an active litigation risk. No current Paragraph IV settlement can preserve its exclusivity after expiration. Historical litigation involving prostaglandin ophthalmic products may have concerned related patents, later formulation patents, or active-ingredient patents rather than this patent alone.

A settlement involving a related patent family should not be interpreted as extending the term of US 5,849,792. Settlement rights are contract-specific and generally do not revive an expired patent.

What is the current generic-launch risk?

The patent itself presents no current generic-launch risk. A generic manufacturer can no longer be enjoined for infringing an expired claim.

The remaining risk for a prostaglandin ophthalmic product is product-specific:

Unexpired Orange Book patents.
Later formulation patents.
Device and container patents.
Method-of-use patents tied to labeling.
Regulatory exclusivity.
Manufacturing patents.
Trade-secret controls over formulation and process parameters.

For an ANDA applicant, the principal pathway is a Paragraph III certification to any unexpired patent with a later launch date, a Paragraph IV challenge to contested patents, or a Section viii statement carving out patented uses where permitted by the labeling and patent scope.[4]

What manufacturing and geographic barriers remain?

US Patent 5,849,792 provides no current geographic exclusivity. Its expiration ended US patent protection for the claimed subject matter. Foreign counterparts must be reviewed separately because foreign patent terms, prosecution outcomes and national-phase claims can differ.

Manufacturing barriers may still arise from:

Control of prostaglandin impurity profiles.
Stereochemical purity.
Hydrolysis and oxidation control.
Surfactant-grade variability.
Sterile filtration and aseptic filling.
Preservative compatibility.
Container-closure adsorption.
Stability over the labeled shelf life.

These are regulatory and technical barriers, not continuing rights under the expired patent.

What are the key business implications?

For licensing, acquisition or litigation screening, US Patent 5,849,792 should be assigned a low current exclusion value and a moderate historical and prior-art value.

For R&D, the patent provides a map of formulation variables that were considered technically effective for prostaglandin stabilization. It does not prevent use of the disclosed composition today.

For generic competition, the relevant diligence should focus on later patents covering the particular reference product, especially travoprost, latanoprost, bimatoprost or preservative-free formulations.

Key Takeaways

US Patent 5,849,792 claims aqueous prostaglandin compositions containing polyethoxylated castor oil, an antimicrobial preservative and a pharmaceutical vehicle.
Claims 2 through 7 narrow the castor-oil concentration and PEG range.
Claim 8 includes latanoprost, fluprostenol isopropyl ester, cloprostenol isopropyl ester and multiple synthetic prostaglandin analogues.
Claim 13 covers topical treatment of glaucoma and ocular hypertension.
The patent expired in 2017 and is not a current US exclusivity barrier.
It does not provide biosimilar protection because prostaglandin ophthalmic products are small-molecule drugs, not biologics.
Current generic risk depends on later active-ingredient, formulation, device, method-of-use and manufacturing patents.
The patent remains relevant as prior art and as a historical formulation reference.

FAQs

Does US Patent 5,849,792 still block generic travoprost?

No. The patent expired in 2017. Generic travoprost risk depends on later unexpired patents and applicable FDA listing and certification requirements.

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

Not under US Patent 5,849,792 because the patent is expired. A separate later patent could cover a specific PEG-35 castor-oil formulation.

Is claim 13 an Orange Book method-of-use claim?

It could have been submitted for listing if it met FDA listing requirements and was associated with an approved product. Its current status cannot create an exclusionary barrier after patent expiration.

Does the patent cover preservative-free ophthalmic prostaglandin products?

No. Each asserted claim requires an antimicrobial preservative, either expressly in the composition claims or through the corresponding limitation in claim 13.

Can a formulation outside the 0.5 wt% to 2.0 wt% range avoid the patent?

It can avoid dependent claim 4, but not necessarily claim 1. Claim 1 has no numerical concentration range and turns on whether the castor oil is present in an amount effective to enhance chemical stability.

References

United States Patent and Trademark Office. (1998). U.S. Patent No. 5,849,792, Aqueous prostaglandin compositions.
United States Code. (2023). 35 U.S.C. § 154: Contents and term of patent; provisional rights.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book.
U.S. Food and Drug Administration. (2009). Guidance for industry: 180-day exclusivity when multiple ANDAs are submitted on the same day.

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: 5,849,792

Summary for Patent: 5,849,792