United States Patent 5,422,368: Scope, Claim Analysis, Expiration and Prostaglandin Glaucoma Patent Landscape

U.S. Patent No. 5,422,368 covers topical ophthalmic prostaglandin compositions for reducing intraocular pressure while limiting ocular irritation. Its broadest practical commercial scope reaches prostaglandin analogs with a substituted aromatic, heteroaromatic, or cycloalkyl omega chain, including latanoprost and closely related phenyl-substituted PGF analogs. The patent issued in 1995 and its U.S. term expired in 2012. It no longer blocks generic manufacture, sale, or use in the United States.

The patent remains important as a historical foundational patent for prostaglandin analog glaucoma therapy, but it has no current exclusionary value. Current U.S. competition is governed by later formulation, manufacturing, dosage-form, and product-specific patents, most of which have also expired for first-generation latanoprost products.

What does U.S. Patent 5,422,368 cover?

The patent claims ophthalmic compositions and treatment methods using selected prostaglandin structures to treat glaucoma or ocular hypertension. The claims require four core elements:

A prostaglandin active ingredient.
A dose sufficient to lower intraocular pressure.
An ophthalmologically compatible vehicle.
A structural profile intended to preserve pressure-lowering activity without substantial ocular irritation.

The patent is not limited to a single named compound in its independent claims. It begins with broad structural genera covering prostaglandins in the PGA, PGB, PGE, PGF, and, in a separate claim set, PGD classes.

The principal structural limitations are:

Structural element	Claimed scope
Alpha chain	Six to 10 carbon atoms
Alpha-chain saturation	Saturated, unsaturated, allene, or triple-bond-containing variants, depending on claim set
Alpha-chain substitution	Alkyl, alicyclic, aromatic, or heteroaromatic substituents
C13-C14 bond	Single, double, or triple bond
D sub-chain	One to 10 carbon atoms; certain claims permit one or two heteroatoms
D-chain substituents	Hydrogen, alkyl, oxo, or hydroxyl
R2 terminal group	Aromatic, heteroaromatic, cycloalkane, or cycloalkene group
Aromatic substitution	Alkyl, alkoxy, trifluoromethyl, acylamino, nitro, halogen, or phenyl groups
Dosage form	Topical ophthalmic composition
Method	Topical treatment of glaucoma or ocular hypertension

The commercial center of gravity is the phenyl-substituted PGF analog covered by claims 20 through 23 and 48 through 51.

Which commercial glaucoma drugs fall within the patent’s claim scope?

The most significant compound identified in the claims is 13,14-dihydro-17-phenyl-18,19,20-trinor-PGF2α isopropyl ester, commonly known as latanoprost.

Claim 22 expressly recites that compound. Claims 20 and 21 cover its ester and alkyl-ester classes, while claim 23 covers the corresponding free-acid prostaglandin. Claims 7, 8, 15 through 18, and 82 through 84 narrow the structure by specifying a PGF2α framework, a three-carbon D chain, a phenyl R2 group, and selected oxidation states at C15.

Latanoprost

Latanoprost is the clearest commercial embodiment:

Active ingredient: latanoprost
Prostaglandin class: PGF2α analog
Terminal group: phenyl
C13-C14 relationship: dihydro, or single-bond configuration
C15: hydroxyl-containing PGF configuration
Ester: isopropyl ester
Indication: reduction of elevated intraocular pressure in open-angle glaucoma or ocular hypertension
Original product: Xalatan
Original sponsor: Pharmacia, later associated with Pfizer commercialization
FDA product type: small-molecule ophthalmic drug
Original NDA: 020597

Latanoprost is within the literal subject matter of several claims, most directly claim 22 and its dependent composition and method claims.

Related prostaglandin analogs

The claim language may also reach structurally related compounds, depending on the exact stereochemistry, esterification, chain configuration, and formulation:

Drug or class	Relationship to Patent 5,422,368
Latanoprost	Directly identified by claim 22
Latanoprost free acid	Addressed by claim 23 and related genus claims
Other alkyl esters of phenyl PGF analogs	Potentially covered by claims 20, 21, 48, and 49
15-dehydro phenyl PGF analogs	Addressed by claims 82 through 87
Travoprost	Structurally related PGF analog; infringement requires comparison against each structural limitation
Bimatoprost	Prostamide rather than a conventional PGF ester; claim coverage is less direct
Tafluprost	Later fluorinated PGF analog; claim-by-claim structural analysis is required
Latanoprostene bunod	Nitric-oxide-donating latanoprost derivative; later product and mechanism

The patent does not automatically cover every prostaglandin eye-drop product. Structural identity or legally sufficient equivalence must be assessed against the alpha chain, C13-C14 bond, D chain, C15 substituent, R2 group, ester group, and formulation limitations.

How are the claims organized?

The 87 claims divide into three principal claim families.

Claims 1 through 28: PGA, PGB, PGE and PGF compositions

Claim 1 is the principal broad composition claim. It covers a topical ophthalmic composition containing PGA, PGB, PGE, or PGF prostaglandin structures with defined alpha and omega chains.

Claims 2 through 23 progressively narrow:

R2 to aromatic rings
R2 to phenyl
D chain length
PGF2α identity
C15 oxo or hydroxyl substitution
isopropyl ester status
13,14-dihydro-17-phenyl-18,19,20-trinor-PGF2α
the specific isopropyl ester associated with latanoprost

Claims 24 through 28 cover topical treatment methods and dose parameters. Claim 28 is particularly narrow, requiring:

Twice-daily application
Approximately 1 to 10 micrograms of prostaglandin
Approximately 10 to 50 microliters of composition

Claims 29 through 56: Expanded D-chain genus

Claim 29 broadens the D sub-chain by permitting one or two heteroatoms selected from oxygen, sulfur, and nitrogen. This creates a separate composition genus that can reach oxygen-, sulfur-, or nitrogen-containing analogs not covered by the carbon-only version of claim 1.

Claims 30 through 51 repeat many of the earlier narrowing limitations, including:

Aromatic or phenyl R2 groups
Three-carbon D chains
PGF2 structures
Isopropyl esters
Alkyl esters of the phenyl-trinor PGF analog

Claims 52 through 56 repeat the method and dosage limitations.

Claims 57 through 75: PGD compositions

Claim 57 is directed specifically to PGD prostaglandins. Its R2 scope is narrower than claim 1 because it recites aromatic and aromatic heterocyclic groups rather than the full cycloalkane or cycloalkene alternative.

Claim 60 identifies heterocyclic terminal groups including thiazole, imidazole, pyrrolidine, thiophene, and oxazole. Claims 61 through 75 narrow the D chain, C15 functionality, phenyl substitution, ester status, dosing, and topical treatment method.

Claims 76 through 87: Position-17 and 15-dehydro analogs

Claims 76 through 81 add a position-17 limitation and convert composition limitations into treatment claims. Claims 82 through 87 specifically address 13,14-dihydro-15-dehydro-17-phenyl-18,19,20-trinor-PGF2α alkyl esters with one to 10 carbon atoms in the alkyl group.

These claims are directed to analogs that differ from latanoprost in the C15 oxidation state or unsaturation pattern. They are more relevant to chemical development programs involving 15-dehydro PGF analogs than to ordinary latanoprost generic products.

What are the strongest and weakest claim features?

Strongest claim features

The most commercially meaningful limitations are the specific compound and ester claims:

Claim 22: the latanoprost compound
Claims 20 and 21: ester and alkyl-ester genus
Claims 48 through 51: corresponding narrowed genus in the expanded D-chain claim set
Claims 82 through 84: 15-dehydro phenyl PGF alkyl esters

These claims identify recognizable chemical structures and are easier to compare with an accused product than the broad functional language in claim 1.

Weaker claim features

Several limitations create potential validity or enforcement vulnerabilities:

"Without causing substantial ocular irritation" is functional and potentially subjective.
The alpha-chain genus is broad relative to the claimed therapeutic result.
The R2 group encompasses multiple unrelated chemical classes.
Claims 24 through 28 and 52 through 56 contain apparent dependency and numbering inconsistencies in the text supplied.
The claims combine broad genus language with limited structural examples, creating potential written-description and enablement issues for the broadest embodiments.
The composition claims may face prior-art issues from earlier prostaglandin pharmacology, ocular hypotensive use, and known ester analogs.
The patent’s term has expired, eliminating the need to resolve most infringement questions for current U.S. commercial activity.

The exact legal effect of the claim inconsistencies must be determined from the certified issued patent and its prosecution history, not from a reformatted claim transcription.

When did Patent 5,422,368 expire?

U.S. Patent 5,422,368 issued on June 6, 1995. Because it belongs to the pre-June 8, 1995 patent-term framework, its ordinary term was generally measured as 17 years from issuance rather than 20 years from the earliest effective nonprovisional filing date. On that basis, the patent expired on June 6, 2012, absent a term adjustment or other unusual term event. The patent is therefore expired and cannot currently support a U.S. patent infringement action.

Event	Date or status
Patent issued	June 6, 1995
Original term framework	Generally 17 years from issue
Expected U.S. expiration	June 6, 2012
Current status	Expired
Current blocking effect	None in the United States

Any historical patent-term-extension or pediatric-exclusivity issue would have required a specific regulatory record. Such extensions generally did not transform the patent into a currently enforceable right.

What was the Orange Book status of Patent 5,422,368?

Patent 5,422,368 was associated with the historical U.S. patent estate for latanoprost ophthalmic products and the Xalatan regulatory franchise. Orange Book relevance depended on whether the patent was submitted and listed against the applicable NDA and whether the listing covered the approved product, formulation, or method of use.

For an ANDA applicant, a listed patent could have required:

Paragraph III certification, accepting delayed approval until expiration;
Paragraph IV certification, asserting noninfringement, invalidity, or unenforceability; or
A certification based on the patent’s lack of relevance to the proposed generic.

Because Patent 5,422,368 expired in 2012, it no longer creates an approval block for a current ANDA. Historical listing status remains relevant to reconstructing earlier generic litigation and launch timing, but it has no present exclusivity effect.

FDA approval exclusivity and patent exclusivity were separate. Latanoprost’s generic entry depended on both the expiration of listed patents and the end of any applicable FDA exclusivity period. FDA small-molecule exclusivity does not create biosimilar-style interchangeability protection.

Which companies challenged latanoprost exclusivity?

The principal challengers to first-generation latanoprost exclusivity were generic-drug companies filing ANDAs after the relevant Orange Book patents and regulatory exclusivities approached expiration. Public generic competition included products from companies such as Mylan, Apotex, Teva, Sandoz, and related generic ophthalmic manufacturers, depending on the specific product and approval period.

The key legal pathway was the Hatch-Waxman ANDA process. A Paragraph IV challenge would have required notice to the NDA holder and could have triggered a 30-month stay if the patent owner filed an infringement action within the statutory period. That stay would have delayed ANDA approval, not necessarily prevented commercial launch after patent expiry.

There is no biosimilar pathway for latanoprost. Latanoprost is a chemically synthesized small molecule, so the relevant competition is generic substitution, not biosimilar approval under the Public Health Service Act.

What patent litigation and settlement issues affected the product?

The principal litigation risk surrounding Patent 5,422,368 was the standard Hatch-Waxman dispute over whether an ANDA product would infringe claims covering latanoprost or a related ophthalmic composition.

A complete litigation assessment requires distinguishing among:

Compound claims;
Composition claims;
Method-of-use claims;
Formulation claims;
Manufacturing claims;
Later patents covering preservative systems, container closure systems, or packaging.

A generic could avoid some claims by using a different formulation, dose, dosing schedule, or manufacturing process. It could not avoid a valid compound claim merely by changing the vehicle if the active ingredient itself fell within the claim.

Publicly reported settlements in the latanoprost field commonly involved licensed early entry, authorized generic arrangements, or agreed launch dates. The expiration of Patent 5,422,368 ultimately removed the patent as a continuing litigation barrier. Settlement terms should not be inferred solely from approval timing because FDA approval, patent expiry, court orders, and commercial launch dates can differ.

How does Patent 5,422,368 compare with competing prostaglandin patent estates?

Product	Active ingredient	Main patent risk profile	Current U.S. position
Xalatan	Latanoprost	Compound, composition, use, and formulation patents	Original patents expired; generic competition established
Travatan Z	Travoprost	Later compound and formulation estate; benzalkonium-chloride-free formulation issues	Generic competition established or developing by product period
Lumigan	Bimatoprost	Prostamide compound, formulation, and use patents	Generic bimatoprost competition established
Zioptan	Tafluprost	Later fluorinated prostaglandin analog and preservative-free formulation estate	Product-specific patent analysis required
Vyzulta	Latanoprostene bunod	Combination prodrug and nitric-oxide mechanism; later formulation and method patents	Later exclusivity profile than latanoprost
Rocklatan	Netarsudil/latanoprost	Combination-product and component-specific patents	Combination-product patent estate

Patent 5,422,368 had greater breadth than a single-product patent because it claimed structural classes across several prostaglandin families. Its practical commercial value was concentrated in latanoprost and related phenyl-substituted PGF analogs.

What formulation and manufacturing barriers remain after patent expiry?

Patent expiry does not eliminate all commercial barriers. A generic ophthalmic manufacturer still must address:

Sterility assurance;
Preservative concentration and compatibility;
pH and osmolality;
Container adsorption and extractables;
Low-dose uniformity;
Active-ingredient degradation;
Particle control;
Drop-size consistency;
Stability after opening;
Manufacturing of the prostaglandin ester;
Control of stereochemistry and impurities.

For latanoprost, the active ingredient is used at a very low concentration. Analytical control and manufacturing reproducibility can be more difficult than the chemical structure alone suggests. These issues are regulatory and technical barriers, not continuing barriers created by Patent 5,422,368.

Later patents may have covered specific formulations, preservative-free systems, packaging, suspension vehicles, or manufacturing intermediates. Such patents must be analyzed separately from the expired 1995 patent.

What is the geographic coverage of Patent 5,422,368?

Patent 5,422,368 provided protection only in the United States. Corresponding foreign rights, if any, depended on separate national patents and their individual filing dates, term calculations, maintenance payments, oppositions, and expiration dates.

A U.S. expiration did not automatically terminate foreign family members. For freedom-to-operate work, the relevant jurisdictions include:

European Patent Office member states;
Japan;
Canada;
Australia;
China;
South Korea;
India;
Brazil.

Foreign patent rights covering latanoprost or related PGF analogs may have expired at different times. U.S. generic launch rights cannot be extrapolated to foreign markets without a country-by-country family review.

What is the current patent strength of Patent 5,422,368?

Its historical claim strength was moderate to high for products containing latanoprost or closely related phenyl PGF analogs. The most useful claims were the compound and ester claims, particularly claim 22. The broad genus claims were more vulnerable to claim-construction, written-description, enablement, and prior-art challenges.

Its current enforceability is zero because the patent has expired. The relevant business question is no longer whether a proposed U.S. product infringes this patent. The relevant question is whether later, unexpired patents cover:

The proposed active ingredient;
A specific formulation;
A preservative-free delivery system;
A manufacturing process;
A combination product;
A method of use;
A device or container system.

Key Takeaways

Patent 5,422,368 claims topical prostaglandin compositions and glaucoma-treatment methods.
Claim 22 directly identifies latanoprost, the isopropyl ester of 13,14-dihydro-17-phenyl-18,19,20-trinor-PGF2α.
Claims 1, 29, and 57 establish broad structural genera covering PGF and other prostaglandin classes.
Claims 24 through 28 and 52 through 56 address topical dosing and administration.
Claims 82 through 87 cover 15-dehydro phenyl PGF alkyl esters.
The patent issued June 6, 1995 and expired in 2012.
It is no longer an enforceable U.S. barrier to latanoprost or related generic products.
Latanoprost competition proceeds through Hatch-Waxman ANDA filings, not biosimilar applications.
Current freedom-to-operate analysis must focus on later formulation, manufacturing, packaging, combination-product, and method-of-use patents.
Foreign family members require separate jurisdiction-specific expiration and validity analysis.

FAQs About U.S. Patent 5,422,368 and Latanoprost Exclusivity

Does Patent 5,422,368 cover Xalatan?

Yes. Claim 22 expressly covers the compound corresponding to latanoprost, and related composition claims cover topical ophthalmic formulations containing the compound.

Can a company launch a latanoprost generic despite Patent 5,422,368?

Yes. The patent expired in 2012, so it no longer prevents U.S. generic manufacture, FDA approval, or commercial sale.

Did Patent 5,422,368 cover travoprost?

Travoprost is structurally related to latanoprost but is not automatically covered. A definitive answer requires mapping travoprost against every limitation of the asserted claim, including the alpha chain, C13-C14 bond, D chain, C15 substituent, R2 group, and ester structure.

Is latanoprost subject to biosimilar competition?

No. Latanoprost is a chemically synthesized small molecule. Its competitors use the ANDA generic-drug pathway under the Hatch-Waxman Act.

Are later latanoprost formulation patents still relevant?

They can be. Expiration of Patent 5,422,368 does not eliminate later patents covering preservative-free formulations, container systems, manufacturing methods, combination products, or other product-specific features.

References

U.S. Patent and Trademark Office. (1995). U.S. Patent No. 5,422,368, Prostaglandin derivatives for the treatment of glaucoma or ocular hypertension. U.S. Department of Commerce.
U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations. Center for Drug Evaluation and Research.
U.S. Food and Drug Administration. (n.d.). Drugs@FDA: FDA-approved drugs, NDA 020597, Xalatan. Center for Drug Evaluation and Research.
U.S. Food and Drug Administration. (n.d.). Orange Book: Approved drug products with therapeutic equivalence evaluations. Center for Drug Evaluation and Research.
U.S. Congress. (1984). Drug Price Competition and Patent Term Restoration Act of 1984, Pub. L. No. 98-417, 98 Stat. 1585.
U.S. Code, 35 U.S.C. §§ 154, 271, and 355.

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Sweden	8803110	Sep 06, 1988
Sweden	8803855	Oct 28, 1988
	PCT/SE89/00475	Sep 06, 1989

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
European Patent Office	0364417	⤷ Start Trial	61/1997	Austria	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 5,422,368

Summary for Patent: 5,422,368