US Patent 9,629,852: Latanoprost Ophthalmic Micro-Emulsion Claims, Expiration, and Patent Landscape

US Patent 9,629,852 protects a narrow latanoprost ophthalmic formulation rather than latanoprost generally. The independent claim requires a specific concentration of latanoprost, castor oil, polyethylene glycol hydroxystearate, a submicron self-emulsifying system, a defined zeta-potential range, an oil-to-surfactant ratio below 1.0, and the absence of cationic surfactants and quaternary ammonium compounds. Claims 2 through 4 add particle-size and optical-transmission limitations. Claim 5 adds a rabbit ocular-irritation limitation.

The patent is relevant to preservative-free or reduced-irritation latanoprost products, including the Xelpros formulation. A conventional latanoprost aqueous solution can generally avoid the literal scope of the claims if it does not contain the claimed oil and polyethylene glycol hydroxystearate micro-emulsion system. The primary commercial risk is therefore directed to generic or follow-on products using a formulation materially similar to the patented emulsion.

What does US Patent 9,629,852 protect?

US 9,629,852 protects a pharmaceutical ophthalmic composition containing the following required elements:

Claim element	Requirement in claim 1
Active ingredient	0.005% w/v latanoprost or pharmaceutically acceptable salt
Oil phase	0.15% w/v castor oil
Surfactant/emulsifier	0.2% to 0.75% w/v polyethylene glycol hydroxystearate
Additional excipients	Co-solvent, chelating agent, preservative, and pharmaceutically acceptable vehicle
Oil-to-surfactant ratio	Less than 1.0
Dosage form	Self-emulsifying micro-emulsion
Droplet size	About 100 nm or less
Zeta potential	Between -0.1 mV and -20 mV
Excluded ingredients	No cationic surfactant and no quaternary ammonium compound

The claim is a combination claim. Each limitation must be considered in assessing literal infringement. A formulation containing latanoprost and castor oil but lacking polyethylene glycol hydroxystearate would not literally satisfy claim 1. The same applies to a formulation with the required excipients but a droplet size above the claimed range or a zeta potential outside the specified range.

The claim also uses several technically significant terms:

"About 100 nm or less" introduces some tolerance around the nominal 100 nm threshold, but its practical scope depends on the specification, testing method, and claim-construction record.
"Self-emulsifying micro-emulsion" requires more than the presence of dispersed oil droplets. The formulation must exhibit the claimed self-emulsifying behavior.
"Ratio of oil to polyethylene glycol hydroxystearate is less than 1.0" appears to refer to the claimed concentrations, producing a ratio of 0.15 divided by the amount of polyethylene glycol hydroxystearate.
The negative limitations exclude both cationic surfactants and quaternary ammonium compounds. A formulation can avoid infringement by using a different surfactant architecture, subject to any doctrine-of-equivalents analysis.

How do dependent claims 2 through 5 narrow the patent scope?

Claims 2 through 5 depend on claim 1 and therefore retain every limitation in the independent claim.

Claim	Added limitation	Commercial significance
2	Average droplet size less than 100 nm	Narrows the particle-size requirement below the approximate 100 nm threshold
3	Claim 2 formulation with transmission greater than 70%	Adds optical clarity/transparency
4	Claim 2 formulation with transmission greater than 80%	Narrows transmission performance further
5	No clinical sign of ocular irritation in rabbits	Adds an animal-tolerability limitation

Claim 4 is narrower than claim 3 because transmission greater than 80% necessarily satisfies transmission greater than 70%. Claims 3 and 4 also inherit the less-than-100-nm particle-size limitation from claim 2.

Claim 5 is potentially important in product testing and litigation. The phrase "does not show any clinical sign of ocular irritation when tested in rabbits" may require evidence under a defined protocol. The patent specification, prosecution history, and testing conditions would affect whether the limitation is interpreted as a structural product characteristic, a result-effective limitation, or a condition requiring proof through the specified assay.

What formulation design choices create infringement risk?

The highest-risk formulation is one that replicates the claimed quantitative profile:

Latanoprost at 0.005% w/v.
Castor oil at 0.15% w/v.
Polyethylene glycol hydroxystearate at 0.2% to 0.75% w/v.
Oil-to-emulsifier ratio below 1.0.
Droplet size of approximately 100 nm or less.
Zeta potential from -0.1 mV to -20 mV.
No cationic surfactant or quaternary ammonium compound.

Potential design-around paths include:

Design-around variable	Possible approach	Key legal or technical issue
Oil phase	Replace castor oil with another oil	Must avoid equivalent composition and equivalent function-risk
Surfactant	Use a non-PEG hydroxystearate emulsifier	Formulation must still achieve stability and ocular tolerability
Active concentration	Use a concentration outside 0.005% w/v	Therapeutic and regulatory comparability may be affected
Droplet size	Produce droplets materially above 100 nm	May change appearance, stability, absorption, and comfort
Zeta potential	Target a value outside the claimed range	Measurement method and batch variability matter
Dosage form	Use an aqueous solution or suspension	May avoid the micro-emulsion limitation
Preservative system	Use a formulation architecture that does not rely on the claimed system	Claim 1 still requires a preservative, so omission could avoid literal scope
Surfactant charge	Use a cationic or quaternary ammonium component	This is expressly excluded by the claim but may create tolerability concerns

The strongest design-around is generally a conventional aqueous latanoprost solution that does not contain the claimed castor-oil/PEG hydroxystearate micro-emulsion. A formulation using a different oil or emulsifier presents a more fact-dependent risk because the patentee could assert the doctrine of equivalents.

When does US Patent 9,629,852 expire?

The patent has a reported patent-term endpoint in February 2032 based on the earliest claimed priority date and the standard 20-year term calculation. Public drug-patent databases identify February 8, 2032 as the relevant expiration date for US 9,629,852. The controlling date should be confirmed against the USPTO Patent Center record, including any patent-term adjustment, terminal disclaimer, or other term event.[1][2]

Event	Date or period
Earliest reported priority date	February 8, 2012
US patent issuance	April 25, 2017
Reported patent expiration	February 8, 2032
Approximate remaining term after issuance	Nearly 15 years
Product relevance	Xelpros latanoprost ophthalmic emulsion

The patent is a formulation patent. It does not create a 20-year monopoly over all latanoprost ophthalmic products. Its enforceable scope is limited by the specific composition and performance limitations in the claims.

What is the FDA and Orange Book status of US 9,629,852?

The patent is associated with Xelpros, a 0.005% latanoprost ophthalmic emulsion. The FDA approved Xelpros under NDA 209534 on May 30, 2018. The product is a prescription ophthalmic emulsion indicated for reduction of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension.[3]

The Orange Book is the key FDA record for determining whether an approved product sponsor has submitted the patent for listing and whether an ANDA applicant must address it through a certification. The patent is publicly associated with Xelpros and its latanoprost ophthalmic emulsion formulation.[2][4]

The FDA regulatory implications are as follows:

A generic applicant seeking approval of an equivalent latanoprost emulsion may need to address the listed patent.
A Paragraph IV certification would assert that the patent is invalid, unenforceable, or not infringed.
A Paragraph III certification would defer approval until patent expiration.
A product that is not pharmaceutically equivalent to Xelpros may pursue a different regulatory route, depending on its formulation and proposed labeling.
Because latanoprost is an established active ingredient, the key regulatory barrier is formulation equivalence and patent certification rather than new chemical-entity exclusivity.

What exclusivity protects Xelpros beyond the patent?

Latanoprost was approved in the United States long before Xelpros. Xelpros therefore did not obtain new chemical entity exclusivity for latanoprost. The relevant FDA exclusivity analysis is based on the approved dosage form, clinical investigations, and any pediatric designation, rather than the active ingredient itself.

The three-year exclusivity framework under the Federal Food, Drug, and Cosmetic Act can apply when an application contains new clinical investigations essential to approval of a new product or formulation. That exclusivity does not block all applications to the same extent as five-year new chemical entity exclusivity and generally does not prevent approval of an ANDA for the same active ingredient if the statutory requirements are satisfied.[5]

The commercial duration of protection is therefore driven primarily by the listed formulation patent, not by a new chemical entity period.

Which products compete with the patented latanoprost emulsion?

The competitive landscape includes both latanoprost products and alternative prostaglandin analogs.

Product or category	Active ingredient	Formulation relevance	Relationship to US 9,629,852
Xelpros	Latanoprost	Ophthalmic emulsion	Commercial product most directly associated with the patent
Generic latanoprost solutions	Latanoprost	Conventional aqueous solution	Often outside the literal emulsion limitations
Xalatan and authorized or generic equivalents	Latanoprost	Aqueous ophthalmic solution	Competes therapeutically but generally differs technically
Travatan Z	Travoprost	Preservative system using sofZia technology	Alternative prostaglandin product
Zioptan	Tafluprost	Preservative-free solution	Competing preservative-free prostaglandin analog
Lumigan	Bimatoprost	Ophthalmic solution	Competing prostaglandin analog
Vyzulta	Latanoprostene bunod	Ophthalmic solution	Different active ingredient and mechanism profile

The patent does not block competing drugs containing travoprost, tafluprost, bimatoprost, or latanoprostene bunod. It may affect only products that adopt the claimed latanoprost micro-emulsion architecture.

What Paragraph IV challenges and litigation risks exist?

A generic applicant can challenge the patent through a Paragraph IV certification if it believes the patent is invalid, unenforceable, or not infringed. The likely litigation issues would include:

Claim construction

The parties would likely dispute:

The meaning of "self-emulsifying micro-emulsion."
The scope of "about 100 nm or less."
Whether zeta potential must be measured under specified conditions.
How the oil-to-polyethylene glycol hydroxystearate ratio is calculated.
Whether the negative limitations exclude trace or incidental quaternary ammonium compounds.
Whether the rabbit-irritation limitation in claim 5 is a meaningful product limitation.

Invalidity

A challenger could assert:

Anticipation by an earlier ophthalmic micro-emulsion disclosure.
Obviousness based on combining latanoprost, castor oil, PEG hydroxystearate, and known nano- or micro-emulsion techniques.
Lack of written description or enablement for the claimed parameter combinations.
Indefiniteness of terms such as "about," "self-emulsifying," or the zeta-potential range.

The strongest patentability issue is likely obviousness. The claimed components are individually familiar formulation excipients, but the patentee can rely on the combination of quantitative ranges, droplet size, zeta potential, optical transmission, and ocular tolerability.

Infringement

A generic product could face infringement exposure if its ANDA formulation contains the same excipients and achieves the claimed physical properties, even if the applicant describes the product using different terminology. Batch testing, formulation records, specifications, and regulatory submissions would be central evidence.

No litigation conclusion should be drawn solely from the presence of an Orange Book listing. A Paragraph IV notice, district-court complaint, settlement, license, or launch-at-risk event must be verified in court and FDA records.

How strong is the patent estate for Xelpros?

The estate appears commercially focused but relatively narrow. US 9,629,852 provides meaningful protection against close copies of the Xelpros emulsion, but it does not create broad protection over:

All latanoprost ophthalmic formulations.
All preservative-free latanoprost products.
All ophthalmic emulsions.
All nano-sized latanoprost dispersions.
Alternative prostaglandin analog products.
Conventional aqueous latanoprost solutions.

Strengths

Multiple quantitative formulation limitations create a specific product fingerprint.
Claims cover both chemical composition and physical performance.
The claim excludes irritancy-associated surfactant classes, supporting a differentiated formulation rationale.
Claims 2 through 4 add narrower particle-size and transmission positions.
A formulation that closely copies the commercial emulsion may be difficult to design around without changing excipients or performance.

Weaknesses

The claim requires a narrow combination of ingredients and parameters.
Generic latanoprost solutions can potentially avoid the claim altogether.
Physical parameters such as zeta potential and droplet size can vary with testing method, dilution, storage, and batch conditions.
Known excipients and emulsion technologies may support an obviousness challenge.
Claim 5 may be difficult to enforce if the rabbit-testing protocol is not clearly defined or reproducible.

What generic launch scenarios are most likely?

Scenario	Patent exposure	Commercial timing
Generic aqueous latanoprost solution	Low literal exposure to US 9,629,852	Dependent on other listed patents and regulatory pathway
Generic version of the Xelpros emulsion	High exposure	Paragraph IV litigation likely if launch is sought before 2032
Alternative latanoprost emulsion using different oil	Moderate, fact-specific exposure	Requires formulation, equivalence, and DOE analysis
Preservative-free latanoprost product using a different vehicle	Potentially lower exposure	Regulatory pathway may differ from an ANDA for Xelpros
Launch after patent expiration	No infringement risk from this patent	Subject to FDA approval and other rights

A first generic entrant would likely evaluate a non-infringing formulation rather than reproduce every limitation. The principal tradeoff is that changing the oil, surfactant, droplet size, or vehicle may undermine bioequivalence, stability, comfort, or approval strategy.

Are licensing deals or settlement agreements publicly established?

The patent is associated with the Xelpros product and its sponsor or commercial rights holder. A definitive licensing arrangement, Paragraph IV settlement, or authorized-generic agreement must be established from a filed agreement, court docket, SEC filing, or FDA submission record. The patent number alone does not establish a license, settlement, or authorized generic.

For transaction diligence, the relevant documents are:

Xelpros NDA ownership and transfer history.
Orange Book patent-listing records.
Paragraph IV notices and related Hatch-Waxman complaints.
Court-filed settlement agreements.
Commercial licensing or supply agreements disclosed by the product sponsor.

What geographic protection exists?

US 9,629,852 provides protection only in the United States. Foreign protection must be assessed through the related international and national-phase patent family. Separate European, Canadian, Australian, Indian, or other national patents may have different claims, expiration dates, prosecution histories, and legal status.

A global launch assessment should not assume that the US claim set applies outside the United States. The central technical concept, however, remains identifiable across jurisdictions: a low-concentration latanoprost ophthalmic self-emulsifying micro-emulsion using castor oil and polyethylene glycol hydroxystearate, with defined droplet-size and electrokinetic properties.

Key Takeaways

US 9,629,852 is a narrow formulation patent directed to a 0.005% latanoprost self-emulsifying ophthalmic micro-emulsion.
The required formulation includes 0.15% castor oil, 0.2% to 0.75% polyethylene glycol hydroxystearate, a co-solvent, chelating agent, preservative, and vehicle.
The composition must have an oil-to-emulsifier ratio below 1.0, droplets of about 100 nm or less, and a zeta potential from -0.1 mV to -20 mV.
The patent excludes cationic surfactants and quaternary ammonium compounds.
Claims 2 through 4 add progressively narrower droplet-size and transmission requirements.
Claim 5 requires no clinical ocular irritation in rabbits.
The reported expiration date is February 8, 2032, subject to the controlling USPTO term record.
Xelpros is the principal commercial product associated with the patent.
Conventional aqueous latanoprost solutions may avoid literal infringement because they do not contain the claimed micro-emulsion system.
The main generic risk is a close copy of the Xelpros formulation or an alternative formulation that still falls within the claim limitations under literal infringement or the doctrine of equivalents.
The patent estate is commercially meaningful but does not broadly cover all latanoprost products or competing prostaglandin analogs.

FAQs About US Patent 9,629,852

Does US 9,629,852 cover generic latanoprost eye drops?

Not categorically. A conventional aqueous latanoprost solution may avoid the patent because claim 1 requires a castor-oil and polyethylene glycol hydroxystearate self-emulsifying micro-emulsion with defined physical properties.

Is Xelpros protected by a composition patent or a method-of-use patent?

US 9,629,852 is principally a composition patent. The supplied claims do not claim treating glaucoma, reducing intraocular pressure, or administering latanoprost as a method of treatment.

Can a generic use a different surfactant?

Potentially. Replacing polyethylene glycol hydroxystearate may avoid literal infringement, but the resulting product must be assessed for doctrine-of-equivalents risk, regulatory equivalence, stability, and ocular tolerability.

Does the patent cover preservative-free latanoprost?

The supplied claim requires a preservative. A preservative-free product may therefore avoid literal infringement of claim 1, although other patents or regulatory requirements may apply.

What patent issue is most important for a Paragraph IV challenge?

The principal issues are likely obviousness of the claimed excipient and parameter combination, construction of "self-emulsifying micro-emulsion," and proof of the claimed droplet-size and zeta-potential ranges in the proposed generic product.

References

United States Patent and Trademark Office. (2017). US Patent No. 9,629,852, ophthalmic pharmaceutical composition. USPTO Patent Center.
United States Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book. FDA.
United States Food and Drug Administration. (2018). Xelpros: Latanoprost ophthalmic emulsion, 0.005% prescribing information. FDA.
United States Food and Drug Administration. (2024). Drugs@FDA: Xelpros, NDA 209534. FDA.
Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 355(j)(5)(F).

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Sun Pharm	XELPROS	latanoprost	EMULSION;OPHTHALMIC	206185-001	Sep 12, 2018		DISCN	Yes	No	9,629,852	⤷ Start Trial	Y				⤷ Start Trial
>Applicant	>Tradename	>Generic Name	>Dosage	>NDA	>Approval Date	>TE	>Type	>RLD	>RS	>Patent No.	>Patent Expiration	>Product	>Substance	>Delist Req.	>Patented / Exclusive Use	>Submissiondate

PCT Information
PCT Filed	October 15, 2008	PCT Application Number:	PCT/IN2008/000671
PCT Publication Date:	July 09, 2009	PCT Publication Number:	WO2009/084021

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2008344909	⤷ Start Trial
Brazil	PI0818459	⤷ Start Trial
Canada	2702478	⤷ Start Trial
China	101835473	⤷ Start Trial
Colombia	6270384	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 9,629,852

Which drugs does patent 9,629,852 protect, and when does it expire?

Summary for Patent: 9,629,852