Details for Patent: 5,889,052

Summary for Patent: 5,889,052

Title:	Use of cloprostenol and fluprostenol analogues to treat glaucoma and ocular hypertension
Abstract:	Disclosed is the use of cloprostenol and fluprostenol analogues for the treatment of glaucoma and ocular hypertension. Also disclosed are ophthalmic compositions comprising said compounds.
Inventor(s):	Peter G. Klimko, John E. Bishop, Verney L. Sallee, Paul W. Zinke
Assignee:	Alcon Research LLC
Application Number:	US08/917,795
Patent Claim Types: see list of patent claims	Use; Composition;

United States Patent 5,889,052 (Glaucoma/Ocular Hypertension; Topical Prostaglandin-Related Stereochemical Formula IV): Scope, Claims, and Landscape

What does US 5,889,052 claim in practical terms?

US 5,889,052 claims methods and topical ophthalmic compositions for treating glaucoma and ocular hypertension using a specific absolute stereochemical “structure (IV)” compound class that is substantially free of the enantiomer. The patent is drafted to cover:

• Therapeutic use: topical dosing to the affected eye to reduce glaucoma/ocular hypertension.
• Active ingredient constraint: compound must have the absolute stereochemical structure (IV).
• Enantiomer restriction: “substantially free of the enantiomer” of the compound having that absolute stereochemical structure.
• Large functional-group space: R1, R2/R3, X, R9, R11, Y, Z define a broad prostaglandin-like scaffold with multiple substituent options.
• Explicit exclusions: one specific compound is excluded from the claim coverage.
• Dose and concentration ranges: method dose in μg/eye; composition concentration in wt %.
• Preferred embodiments: certain named compounds and specific parameter combinations.

What is the core independent claim structure?

The claims separate into two independent claim “families”:

Claim family A: Method (claims 1–11)

• Claim 1 is the method of treating glaucoma and ocular hypertension by topically administering a therapeutically effective amount of the Formula (IV) stereochemical compound that is substantially free of the enantiomer.
• Dependent claims narrow the Formula (IV) variables, specify exemplars, and define dose ranges.

Claim family B: Composition (claims 12–22)

• Claim 12 is a topical ophthalmic composition comprising an ophthalmically acceptable carrier and the Formula (IV) stereochemical compound, again with the substantially free of enantiomer requirement, plus the same scaffold parameter set and exclusions.
• Dependent claims narrow scaffold parameters and define concentration ranges.

What exactly is inside “Formula (IV)”?

The patent defines a parameterized prostaglandin-like chemical scaffold. Coverage depends on the selection of substituents and stereochemical relationships tied to the alpha/omega chain and Y/OR15 configuration.

Key structural parameters (as recited)

For both the method and composition claims, the compound must have the absolute stereochemical structure of Formula (IV) with the following definitions:

• R1:

  • H
  • or C1–C12 straight-chain or branched alkyl
  • or C1–C12 straight-chain or branched acyl
  • or C3–C8 cycloalkyl (composition claim set specifies C3–C8; method claim set specifies C3–C3 cycloalkyl)
  • or a cationic salt moiety

• R2, R3:

  • each is H, or C1–C5 straight-chain or branched alkyl
  • or R2 and R3 taken together represent O

• X: O, S, or CH2

• Unsaturation pattern:
  Formula states X “represents any combination of a single bond, or a cis or trans double bond for the alpha (upper) chain; and a single bond or trans double bond for the omega (lower) chain.”

• R9, R11: each is H, or C1–C10 alkyl, or C1–C10 acyl

• Y: either O or H and OR15 (in either configuration)

• R15: H or C1–C10 alkyl or C1–C10 acyl (when Y is H and OR15)

• Z: Cl or CF3

Claim-specific provisos that narrow the allowed combinations

Two structural “provisos” control exclusion of certain embodiments:

1. If R2 and R3 together = O, then R1 ≠ C1–C12 straight-chain or branched acyl
2. If R2 = R3 = H, then R1 ≠ a cationic salt moiety

These provisos block overlap with particular esterification states when the 2,3-positions form an oxygen bridge, and block cationic salts when both R2 and R3 are H.

What compound is explicitly excluded?

Both claim sets exclude this specific compound:

• “cyclopentane heptenol-5-cis-2-(3-αhydroxy-4-m-chlorophenoxy-1-transbutenyl)-3,5 dihydroxy, 1.α, 2.β, 3.α, 5.α”
  (Exact typography differs slightly between the method and composition text, but the exclusion is the same.)

This exclusion is a meaningful landscape signal: it carves out at least one otherwise plausible match within the prostaglandin-like scaffold space.

What are the dependent-claim exemplars?

The claims name a small set of specific stereochemical embodiments:

Method

• Claim 6: compound (IV) selected from:
  • 3-oxacloprostenol
  • 13,14-dihydrofluprostenol
  • and their pharmaceutically acceptable esters and salts
• Claim 8: 13,14-dihydrocloprostenol pivaloate

Composition

• Claim 17: compound (IV) selected from:
  • 3-oxacloprostenol
  • 13,14-dihydrofluprostenol
  • and their pharmaceutically acceptable esters and salts
• Claim 19: dihydrocloprostenol pivaloate

What dose range does the patent claim for the method?

The method claims define increasing specificity:

• Claim 9: about 0.01 to 1000 μg/eye
• Claim 10: about 0.1 to 100 μg/eye
• Claim 11: about 0.1 to 10 μg/eye

These ranges cover a wide dosing window, and the narrower ranges become additional patent hooks for formulation and regimen planning.

What concentration ranges does the patent claim for the composition?

The composition claims define wt % bands:

• Claim 20: about 0.0003 to 0.3 wt %
• Claim 21: about 0.0003 to 0.3 wt % (same band repeated in the text)
• Claim 22: about 0.003 to 0.03 wt %

How broad is the patent’s stereochemical scope?

The patent’s scope is primarily defined by two interacting constraints:

1. Absolute stereochemical structure (IV): you must be in the defined stereochemical series, not just “a prostaglandin analog.”
2. Enantiomer exclusion: the claimed compound must be “substantially free of the enantiomer.”

That pairing creates a common patent design: capture the single-enantiomer drug substance (or enantiomer-enriched preparation) and its topical use.

What is the practical claim “ladder” for narrowing?

Method claim ladder (1 → 11)

1. Claim 1: method + generic Formula (IV) parameter set + enantiomer constraint + glaucoma/ocular hypertension.
2. Claim 2: tightens stereochemical configuration for alpha/omega unsaturation (X=CH2; cis alpha and trans omega) and Y alpha/beta OH/H pattern.
3. Claim 3: narrows Z=CF3.
4. Claim 4–5: selects R2/R3/O states and narrows X (O or CH2), R9/R11=H, Y=H and OR15 with R15=H.
5. Claim 6: specifies named exemplars (3-oxacloprostenol; 13,14-dihydrofluprostenol; esters/salts).
6. Claim 7–8: refines R1 and gives a named pivaloate example.
7. Claim 9–11: dosing ranges.

Composition claim ladder (12 → 22)

1. Claim 12: topical ophthalmic composition + generic Formula (IV) parameter set + enantiomer constraint.
2. Claim 13: fixes specific stereochemical and unsaturation features (X=CH2; cis alpha/trans omega; R9/R11=H; Y alpha OH and beta H).
3. Claim 14: narrows Z=CF3.
4. Claim 15–16: locks in R2/R3 = H,H or O; chooses X=O or CH2; R9/R11=H; defines Y=H and OR15 with R15=H; sets R1 limits.
5. Claim 17–19: exemplars (3-oxacloprostenol; 13,14-dihydrofluprostenol; esters/salts; and dihydrocloprostenol pivaloate).
6. Claim 20–22: concentration ranges.

Where does the patent likely sit in the broader glaucoma prostaglandin landscape?

Within glaucoma therapy, prostaglandin analogs dominate topical intraocular pressure reduction. This patent is aimed at the single-enantiomer and specific stereochemical compound set inside a prostaglandin-like family, with additional levers for:

• ester/salt forms (explicitly included in the named exemplars’ scope)
• specific halogen pattern (Z=Cl or CF3, with a dependent claim narrowing to CF3)
• alpha/omega double bond stereochemical arrangement (cis alpha and trans omega specified in dependent claims)
• dose/concentration windows that enable practice even if exact drug substance varies within the scaffold space

In business terms, the claim strategy is designed to stop competitors who attempt to launch a “near-proxy” stereochemical analog with a different delivery profile. The enantiomer constraint and explicit exclusions reduce risk of reading broadly over all prostaglandin analogs, but the broad variable coverage for R groups means the patent can still reach multiple stereochemical variants that stay within the stereochemistry framework.

Scope risk map: what competitor design-outs are likely to avoid infringement?

Using only the claim text, the most direct design-out routes are:

• Avoid the Formula (IV) absolute stereochemistry series: the claims require “absolute stereochemical structure of the following formula (IV).”
• Avoid enantiomer-enriched preparations: the claims require “substantially free of the enantiomer.” A formulation that is not “substantially free” can fall outside this specific claim language.
• Hit the proviso exclusions:
  • If R2 and R3 together represent O, ensure R1 is not acyl in the claimed form.
  • If R2=R3=H, ensure R1 is not a cationic salt moiety.
• Avoid the explicitly excluded compound (the cyclopentane heptenol derivative named in the claims).
• Dose/concentration escape only protects against method/composition claims if outside bands, but cannot fully avoid claim 1/12 unless the infringement is shifted to a different claim set that still covers the alternative dosing.

Patent landscape implications for freedom-to-operate (FTO)

Given the structure of claims 1 and 12:

• Any topical glaucoma/ocular hypertension product using a substantially enantiomer-free Formula (IV) stereochemical compound with the stated parameter set can fall within coverage.
• A competitor can still practice the active in the clinic while avoiding literal infringement only by moving out of the specific stereochemical/enantiomer constraints or out of the defined parameter space.
• Ester and salt scope is explicitly captured where exemplars are listed (e.g., “and their pharmaceutically acceptable esters and salts”), so prodrugs or salt-form switches likely do not provide an easy escape if the resulting molecule still maps to the claimed scaffold and stereochemical series.

Key Takeaways

• US 5,889,052 claims topical glaucoma/ocular hypertension treatment with a single absolute stereochemical “Formula (IV)” compound class that is substantially free of the enantiomer.
• The scaffold is defined by multiple substituent variables (R1, R2/R3, X, R9, R11, Y/OR15, Z) and controlled by two proviso exclusions and one explicit compound exclusion.
• Claim coverage extends to method dosing (0.01 to 1000 μg/eye; with narrower 0.1 to 10 μg/eye) and composition concentration (0.0003 to 0.3 wt %; plus 0.003 to 0.03 wt %).
• The patent includes named exemplars that act as clear claim anchors: 3-oxacloprostenol, 13,14-dihydrofluprostenol, 13,14-dihydrocloprostenol pivaloate, and dihydrocloprostenol pivaloate.
• For landscape and FTO, the highest-risk factor is the combination of stereochemical series + enantiomer-enriched drug substance used in topical ophthalmic dosing.

FAQs

1) Does the patent cover all glaucoma treatments?

No. It covers topically administering a therapeutically effective amount of a Formula (IV) stereochemical compound that is substantially free of the enantiomer for treating glaucoma and ocular hypertension.

2) Is the claim limited to a single drug molecule?

No. The claims use a parameterized Formula (IV) that can vary across multiple substituent classes (alkyl/acyl/cycloalkyl/cationic salt moiety, X=O/S/CH2, Z=Cl/CF3, and multiple stereochemical and configuration-defined features), subject to provisos and exclusions.

3) What is the main legal lever: stereochemistry or enantiomer purity?

Both. The claims require the compound to have the absolute stereochemical structure of Formula (IV) and to be substantially free of the enantiomer.

4) Does the patent cover both method-of-use and product?

Yes. It covers:

• A method (claims 1–11) and
• A topical ophthalmic composition (claims 12–22), with overlapping scope defined by the same Formula (IV) and enantiomer constraint.

5) Are dose and concentration limits part of infringement?

For the respective claim types, yes:

• Method claims include μg/eye ranges in dependent claims.
• Composition claims include wt % concentration ranges in dependent claims. Literal coverage of independent claims does not hinge on those dependent ranges, but they matter for narrowing embodiments.

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References

[1] United States Patent US 5,889,052. “Method of treating glaucoma and ocular hypertension and ophthalmic compositions.” (Claims excerpt provided in prompt).

Drugs Protected by US Patent 5,889,052

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate

International Family Members for US Patent 5,889,052

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	1514548		C300671	Netherlands
European Patent Office	1514548		PA2014029	Lithuania
European Patent Office	1514548		CA 2014 00038	Denmark
European Patent Office	1920764		CA 2012 00030	Denmark
European Patent Office	1920764		92058	Luxembourg