United States Patent 6,429,226: Claim Scope, Latanoprost Coverage, Expiration and Patent Landscape

U.S. Patent No. 6,429,226 covers topical ophthalmic compositions containing phenyl-substituted prostaglandins for lowering intraocular pressure, including latanoprost and closely related PGF2α analogs. The broadest practical commercial claim is claim 29, which recites a PGF2α prostaglandin with a 13,14 double bond, a 15-hydroxyl group, and an unsubstituted 17-phenyl group. That structural description reads on latanoprost.

The patent is no longer an active barrier to U.S. generic entry. Latanoprost generic products received FDA approval and entered the market after expiration or loss of enforceability of the relevant pioneering patent estate. Current commercial risk has shifted from this patent to formulation, device, preservative-free delivery, manufacturing, and combination-product patents.

What does U.S. Patent 6,429,226 cover?

U.S. Patent 6,429,226 covers ophthalmic compositions and methods using phenyl-substituted prostaglandin analogs to treat glaucoma or ocular hypertension. The claims require:

Topical ophthalmic administration;
Treatment of humans;
Reduction of intraocular pressure;
An ophthalmologically compatible vehicle;
A prostaglandin of the PGA, PGB, PGE, or PGF series;
A specified omega-chain structure ending in a phenyl group; and
Sufficient drug concentration to reduce intraocular pressure without substantial ocular irritation.

The patent has two principal independent composition claims and two corresponding method claims:

Claim	Type	Principal scope
1	Composition	PGA, PGB, PGE or PGF analog with a 3-carbon D subchain, hydroxyl substituent, and substituted or unsubstituted 17-phenyl group
2	Method	Topical human treatment using a composition of claim 1
15	Composition	Broader 2-to-5-carbon D subchain with hydroxyl or oxo substitution at C15 and terminal phenyl group
16	Method	Topical human treatment using a composition of claim 15
29	Composition	PGF2α, 13,14 double bond, 15-hydroxyl, and unsubstituted 17-phenyl group

The claims are composition claims, not claims limited to a particular branded product, bottle, preservative, dosage strength, or dosing schedule.

Which commercial drug does U.S. Patent 6,429,226 cover?

Claim 29 reads on latanoprost, the active ingredient in Xalatan.

Latanoprost is commonly identified as:

13,14-dihydro-17-phenyl-18,19,20-trinor-PGF2α isopropyl ester;
A PGF2α analog;
A prodrug hydrolyzed in the eye to latanoprost acid; and
A topical ocular hypotensive agent.

The supplied claim set expressly identifies several relevant analogs:

Claim	Named compound or structural class	Commercial relevance
11	17-phenyl-18,19,20-trinor-PGF2α isopropyl ester	Latanoprost-related structure
12	15-(R)-17-phenyl-18,19,20-trinor-PGF2α isopropyl ester	Stereochemical analog
13	13,14-dihydro-17-phenyl-18,19,20-trinor-PGF2α isopropyl ester	Latanoprost
26	15-(R)-13,14-dihydro-17-phenyl-18,19,20-trinor-PGF2α isopropyl ester	Latanoprost-related analog
29	PGF2α with 13,14 double bond, C15 hydroxyl, and unsubstituted 17-phenyl	Broad structural coverage of latanoprost

The patent does not require the composition to contain only the claimed prostaglandin. The word "containing" generally permits additional ingredients, including buffers, tonicity agents, preservatives, surfactants, viscosity modifiers, and other compatible components.

How broad are the independent claims?

Claim 1: broad genus with a three-carbon omega-chain subchain

Claim 1 requires a prostaglandin whose omega chain has:

A C13-B-C14 linkage;
B as either a single or double bond;
A three-carbon D subchain;
A hydroxyl group on the D subchain; and
An unsubstituted or substituted 17-phenyl group.

The claim reaches both saturated and unsaturated C13-C14 variants. It also reaches a wide range of phenyl substitutions, including:

C1-C5 alkyl;
C1-C4 alkoxy;
Trifluoromethyl;
C1-C3 aliphatic acylamino;
Nitro; and
Phenyl.

The claim is therefore not limited to latanoprost. It covers a genus of phenyl-substituted prostaglandin analogs having a defined side-chain architecture.

Claim 15: broader chain-length and oxidation-state coverage

Claim 15 broadens the D subchain from three carbons to two through five carbons. It also permits either:

A hydroxyl group at C15; or
An oxo group at C15.

This creates broader chemical coverage than claim 1 in two directions: chain length and oxidation state. Claim 15 also uses "terminal phenyl group," which is structurally broader in wording than the "17-phenyl" language in claim 1, although the practical scope depends on how the patent specification and prosecution history define the terminal group.

Claim 29: narrower but commercially important

Claim 29 narrows the genus to a particular PGF2α architecture:

PGF2α prostaglandin;
C13-C14 double bond;
Three-carbon D subchain;
Hydroxyl substituent at C15; and
Unsubstituted 17-phenyl group.

This claim is easier to map to a commercial molecule than claims 1 and 15. It also provides a more direct infringement theory for a product containing latanoprost than the broader genus claims.

What formulations are protected by U.S. Patent 6,429,226?

The patent protects the active pharmaceutical composition at a functional and structural level. It does not appear, from the supplied claims, to require a particular formulation architecture.

Potentially covered formulations include topical ophthalmic solutions containing the claimed prostaglandin and an ophthalmically compatible vehicle, such as:

Preserved aqueous solutions;
Buffered solutions;
Isotonic or near-isotonic solutions;
Solutions containing benzalkonium chloride;
Solutions containing surfactants or solubilizers; and
Formulations with excipients used to maintain chemical stability or ocular tolerability.

The claims do not expressly require:

Benzalkonium chloride;
A specific pH;
A specific concentration;
A specific bottle or dropper;
A particular dosing frequency;
A suspension or emulsion;
A preservative-free formulation; or
A particular salt, ester, or prodrug beyond the structural limitations.

The limitation requiring an amount "sufficient to reduce intraocular pressure without causing substantial ocular irritation" is important. It is a functional limitation that links the composition to therapeutic efficacy and tolerability. A product containing the claimed molecule in a concentration that does not lower intraocular pressure, or that causes substantial ocular irritation, would present a different infringement analysis.

How do the dependent claims narrow the patent?

The dependent claims add stereochemical, structural, and pharmacological restrictions.

Claim group	Limitation
Claims 3, 17	C13-C14 single bond
Claims 4, 18, 28, 29	C13-C14 double bond
Claims 5, 9, 19, 29	Unsubstituted phenyl group
Claims 6, 24	Substituted phenyl group
Claims 7, 25	PGF prostaglandin
Claim 8	Hydroxyl group at C15
Claims 10, 12, 26	15-(R) stereochemistry or related named analog
Claim 27	15-(S) stereochemistry
Claims 20, 22	C15 hydroxyl
Claims 21, 23	C15 oxo
Claim 28	PGF analog with a double bond
Claim 29	Specific PGF2α phenyl analog genus

Claim 29 is particularly significant because it combines the characteristics associated with latanoprost: a PGF2α backbone, a 13,14 double bond, a C15 hydroxyl, and an unsubstituted 17-phenyl group.

Claim 28 contains the phrase "PGF60," which appears to be a typographical error or transcription issue. The surrounding claims and structural context indicate that PGF2α was likely intended. A court would evaluate the issued patent, prosecution history, certificate of correction, and surrounding claim language rather than a secondary transcription.

When did U.S. Patent 6,429,226 lose exclusivity?

The patent is expired and does not currently block generic commercialization of latanoprost in the United States.

For a pre-1995 U.S. application, the patent term generally followed the former 17-years-from-issuance framework, subject to terminal disclaimers, patent-term adjustments, patent-term extensions, and other statutory modifications. For a post-1995 application, the ordinary term is generally 20 years from the earliest effective nonprovisional filing date under 35 U.S.C. § 154.

The relevant practical timeline is:

Event	Timing
Patent issued	August 6, 2002
Branded product	Xalatan, latanoprost ophthalmic solution
FDA generic pathway	ANDA litigation and Paragraph IV challenges
Generic market entry	Early 2010s
Current patent status	Expired; no current blocking exclusivity from U.S. 6,429,226

The exact statutory expiration date should be taken from the USPTO patent term record for the issued patent and any related continuation or terminal-disclaimer records. The patent’s commercial importance ended when the applicable patent and regulatory exclusivity barriers no longer prevented approved generic latanoprost products from entering the market.

What was the Orange Book status of latanoprost?

Latanoprost was listed in the FDA Orange Book in connection with Xalatan and related approved products. Orange Book-listed patents can create ANDA certification obligations under the Hatch-Waxman Act.

For an ANDA applicant, the principal certification options are:

Paragraph I: no patent information was submitted;
Paragraph II: the patent has expired;
Paragraph III: the applicant will wait until expiration; or
Paragraph IV: the patent is invalid, unenforceable, or will not be infringed.

Latanoprost generic applicants used the ANDA pathway. The relevant commercial dispute centered on patents covering latanoprost and its use in reducing intraocular pressure, rather than on biosimilar regulation. Latanoprost is a chemically synthesized small molecule, so biosimilar provisions under the Public Health Service Act do not apply.

Which companies challenged latanoprost patents?

The principal challengers to the U.S. latanoprost estate included generic ophthalmic manufacturers and distributors seeking ANDA approval. Publicly reported participants included:

Apotex;
Mylan, now part of Viatris;
Teva-related generic operations;
Watson Pharmaceuticals, later part of Actavis and Allergan; and
Other ANDA applicants approved by FDA over time.

The precise challenger for a particular patent depends on the patent, ANDA number, notice letter, district-court action, and settlement record. U.S. Patent 6,429,226 should not be treated as interchangeable with the better-known pioneering latanoprost patents. The relevant litigation record may involve related patents in the same product family rather than this patent alone.

What patent litigation affected Xalatan and latanoprost?

The core U.S. disputes involved:

Validity challenges to latanoprost compound claims;
Non-infringement arguments based on the specific structure of the proposed generic;
Orange Book certification disputes;
Patent-term and expiration-date issues;
Regulatory approval timing; and
Settlements governing the timing of generic launch.

The commercial outcome was generic entry in the early 2010s. That outcome indicates that the relevant patent estate no longer supported a durable U.S. monopoly over latanoprost.

A Paragraph IV certification is not itself proof that a patent is invalid or uninfringed. It creates a statutory basis for patent litigation and, if the NDA holder files suit within the statutory period, can trigger a regulatory stay. The ultimate commercial effect depends on the court decision, settlement, patent expiration, and FDA approval timing.

Are there settlement agreements for latanoprost patents?

Latanoprost patent challenges generated the type of generic-brand settlement activity common in ophthalmic products with significant pre-expiration revenue. Settlement terms can include:

An agreed generic entry date;
Authorized-generic arrangements;
Restrictions on launch timing;
Allocation of patent claims between products; and
Resolution of pending infringement actions without a final validity ruling.

A settlement does not establish that U.S. Patent 6,429,226 was valid. It also does not extend the patent term. Its commercial effect depends on the agreed entry date and the patents expressly covered by the agreement.

How strong is the patent estate for latanoprost?

The estate was strong during the protected commercial period because it combined several forms of protection:

Protection type	Strategic value
Compound claims	Covered the active latanoprost structure and related analogs
Composition claims	Covered topical ophthalmic products containing the prostaglandin
Method-of-use claims	Covered treatment of glaucoma and ocular hypertension
Formulation claims	Could address concentration, preservatives, stability, or tolerability
Regulatory exclusivity	Delayed ANDA competition independently of patent validity
Manufacturing patents	Could complicate production of the active ingredient or intermediates

The supplied claims are strongest against a generic that uses latanoprost in a conventional topical ophthalmic solution. They are weaker against:

A non-phenyl prostaglandin analog;
A structurally distinct prostamide;
A different therapeutic class;
A product using a different active ingredient;
A non-ocular formulation; or
A formulation introduced after expiration where only later-added formulation patents remain relevant.

Because the patent is expired, current strength is historical rather than exclusionary.

How does this patent compare with competing glaucoma-drug patent estates?

Drug	Active ingredient	Class	Relevance to U.S. 6,429,226
Xalatan	Latanoprost	Prostaglandin F analog	Directly implicated
Travatan	Travoprost	Prostaglandin F analog	Similar therapeutic class, different structure and patent estate
Lumigan	Bimatoprost	Prostamide	Separate compound and formulation patents
Zioptan	Tafluprost	Prostaglandin F analog	Separate compound and preservative-free formulation estate
Rhopressa	Netarsudil	Rho kinase inhibitor	Separate small-molecule and formulation estate
Vyzulta	Latanoprostene bunod	Nitric oxide-donating prostaglandin analog	Separate compound and method claims
Cosopt	Dorzolamide/timolol	Carbonic anhydrase inhibitor/beta blocker	Combination-product estate

The key distinction is that structural similarity does not automatically create infringement. Travoprost, tafluprost, bimatoprost, and latanoprost have different chemical structures and were protected by separate patent families.

What manufacturing and intellectual-property barriers remain?

The expiration of U.S. 6,429,226 removed one barrier but did not eliminate all entry risks for ophthalmic products. Remaining barriers can include:

Active pharmaceutical ingredient manufacturing

Latanoprost production requires control of:

Stereochemistry;
Double-bond configuration;
Esterification;
Impurity profiles;
Residual solvents;
Degradation products; and
Batch-to-batch potency.

Manufacturing patents covering intermediates or processes can create freedom-to-operate issues even after composition claims expire. These rights are separate from the claims supplied.

Formulation and packaging

Later patents may cover:

Preservative-free latanoprost;
Low-volume dosing;
Multidose preservative-free containers;
Improved chemical stability;
Reduced ocular surface toxicity;
Nanoparticle or emulsion delivery;
Contact-lens delivery; and
Combination formulations.

A generic product may avoid an expired composition patent while still requiring a separate analysis of current formulation and packaging patents.

FDA requirements

FDA approval requires pharmaceutical equivalence, bioequivalence or applicable product-specific testing, manufacturing compliance, stability data, labeling, and container-closure qualification. For ophthalmic solutions, sterility and particulate-control requirements create practical barriers even where patent barriers have expired.

What generic launch scenarios existed for latanoprost?

The market supported several launch paths:

A conventional generic latanoprost ophthalmic solution using the same active ingredient and a comparable vehicle.
A formulation designed around a different preservative or preservative concentration.
A preservative-free product using a specialized multidose container.
An authorized generic or settlement-based launch before complete patent expiry.
A product launched after Orange Book patents expired or became subject to Paragraph II certification.

The first scenario created the most direct exposure under the claims supplied. Once the patent expired, a conventional latanoprost generic no longer faced infringement risk from U.S. 6,429,226, although other patent and regulatory issues could remain.

What is the geographic coverage of U.S. Patent 6,429,226?

The patent has U.S. territorial scope. It can be asserted against:

Manufacture in the United States;
Use in the United States;
Sale or offer for sale in the United States;
Importation into the United States; and
ANDA activity that falls within the statutory infringement framework.

The patent does not directly control sales in Europe, Japan, Canada, or other jurisdictions. Foreign counterparts require separate review of national filing dates, grant status, validity, supplementary protection certificates, pediatric extensions, and local litigation.

Key Takeaways

U.S. Patent 6,429,226 covers topical phenyl-substituted prostaglandin compositions for glaucoma and ocular hypertension.
Claim 29 is the most commercially relevant claim because it reads on the structural class containing latanoprost.
Claims 1 and 15 are broader genus claims covering multiple phenyl prostaglandin analogs, chain lengths, bond configurations, and C15 oxidation states.
The patent covers compositions and treatment methods, not merely a named brand.
The claims do not require a particular preservative, concentration, pH, bottle, or dosing schedule.
Latanoprost is a small molecule, so biosimilar law is irrelevant. Generic competition proceeds through the ANDA pathway.
The patent is expired and no longer provides current U.S. exclusivity.
Current latanoprost entry risk is more likely to arise from later formulation, delivery, manufacturing, or combination-product patents.
Travoprost, bimatoprost, tafluprost, netarsudil, and latanoprostene bunod have separate patent estates.
The patent’s historical commercial value was substantial because it supported protection for a leading prostaglandin glaucoma product, but its present exclusionary value is zero after expiration.

FAQs About U.S. Patent 6,429,226 and Latanoprost Exclusivity

Does U.S. Patent 6,429,226 cover Xalatan?

Yes. The structural limitations in claim 29 correspond to latanoprost, the active ingredient in Xalatan.

Can a generic company still infringe U.S. Patent 6,429,226?

A product that would have infringed during the patent term generally cannot be enjoined today solely on the basis of this expired patent. Expired claims cannot support prospective patent exclusion.

Is latanoprost protected by a biologic patent or biosimilar pathway?

No. Latanoprost is a chemically synthesized small molecule regulated through the NDA and ANDA framework, not the biologic-license and biosimilar framework.

Do preservative-free latanoprost products fall within the claims?

They may fall within the expired composition claims if they contain the claimed latanoprost structure in an ophthalmically compatible vehicle. Preservative-free status does not by itself avoid the structural limitations.

Are patents on latanoprost manufacturing still commercially relevant?

Yes. Process, intermediate, impurity-control, formulation, container, and delivery patents can create separate freedom-to-operate issues even after the main compound and composition patent has expired.

References

U.S. Patent No. 6,429,226. (2002). Ophthalmic prostaglandin compositions. United States Patent and Trademark Office.
U.S. Food and Drug Administration. (2024). Orange Book: Approved drug products with therapeutic equivalence evaluations. https://www.accessdata.fda.gov/scripts/cder/ob/
U.S. Food and Drug Administration. (2023). Xalatan (latanoprost ophthalmic solution) prescribing information. Pfizer Laboratories.
U.S. Patent and Trademark Office. (2024). Patent term adjustment and patent term extension information. https://www.uspto.gov/
U.S. Food and Drug Administration. (2024). Drugs@FDA: FDA-approved drugs database. https://www.accessdata.fda.gov/scripts/cder/daf/

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Sweden	8803110	Sep 06, 1988
Sweden	8803855	Oct 28, 1988

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	0364417	⤷ Start Trial	SPC/GB97/014	United Kingdom	⤷ Start Trial
European Patent Office	0364417	⤷ Start Trial	97C0128	France	⤷ Start Trial
European Patent Office	0364417	⤷ Start Trial	9690031-1	Sweden	⤷ Start Trial
European Patent Office	0364417	⤷ Start Trial	97C0111	Belgium	⤷ Start Trial
European Patent Office	0364417	⤷ Start Trial	C970039	Netherlands	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 6,429,226

Summary for Patent: 6,429,226