Details for Patent: 7,273,946

Summary for Patent: 7,273,946

Title:	Prostaglandin derivatives
Abstract:	Prostaglandin nitroderivatives having improved pharmacological activity and enhanced tolerability are described. They can be employed for the treatment of glaucoma and ocular hypertension.
Inventor(s):	Eninnio Ongini, Valerio Chiroli, Francesca Benedini, Piero Del Soldato
Assignee:	Nicox SA
Application Number:	US11/029,698
Patent Claim Types: see list of patent claims	Use; Composition; Dosage form;

US Patent 7,273,946: What Is the Scope of Claims and Where Does the Landscape Land?

United States Patent No. 7,273,946 defines a family of prostaglandin-residue linked “nitrooxy” (ONO2-containing) ether/amides/analogues through general Formula (I) and sets out structural limits in dependent claims, plus a preparation process and ocular-use compositions and methods (glaucoma/ocular hypertension).

The claims you provided are heavily Markush-style, with broad tolerances for linker length, heteroatom insertion, and optional substitution patterns, while anchoring the core pharmacophore as a prostaglandin residue (travoprost, unoprostone, cloprostenol, or latanoprost per dependent claims 4-5). The practical commercial scope is therefore the intersection of:
1) prostaglandin “tail” identity,
2) specific ONO2-linking geometry and linker families, and
3) ocular formulation/use claims.

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What Does Claim 1 Actually Cover Under Formula (I)?

Core structure in Claim 1

Claim 1 covers a compound of general Formula (I):

• R—X—Y—ONO2 (I)
  where:
  • R is the prostaglandin residue of Formula (II) (the prostaglandin scaffold is the moiety that sets the prostaglandin identity).
  • X is selected from —O—, —S—, —NH—.
  • Y is a bivalent radical that links X to the ONO2-bearing terminus.
  • ONO2 is explicitly the terminal nitrooxy functionality.

Y is the main scope lever

Claim 1 defines Y as an alkylene/cycloalkylene/linked-alkylene/heterocycle-adjacent family with variables:

• Straight or branched C1-C20 alkylene, optionally substituted with:
  • halogen
  • hydroxy
  • —ONO2
  • T, where T is either:
  • —OC(O)(C1-C10 alkyl)—ONO2, or
  • —O(C1-C10 alkyl)—ONO2
• Cycloalkylene (5 to 7 carbons) with optional alkyl side chains T1 (C1-C10).

It then provides additional nested structural definitions involving:

• integer ranges n (0 to 20) and n1 (1 to 20)
• X1 options —OCO— or —COO—
• R2 is H or CH3
• Z is —(CH)n1— or a defined bivalent analogue (per further subcases)
• additional nested sequences n2 (0 to 2), n3 (1 to 6), n4 (0 to 10), n5 (1 to 10)
• R3 is H or —COCH3
• terminal heterocycle Y2 constraints with 5- or 6-member saturated/unsaturated/aromatic rings containing N/O/S.

Key boundary conditions

Claim 1 also includes a specific proviso that constrains where the ONO2 sits in certain Y subcases:

• Proviso: when Y is selected from the bivalent radicals mentioned under b)-f), the —ONO2 group is bound to —(CH2)n1.

That clause prevents total positional freedom of ONO2 in those subfamilies and forces a particular connectivity for the nitrooxy terminus.

Practical interpretation of Claim 1 coverage

Even with the dense Markush complexity, Claim 1 has a recognizable “design template”:

• Choose one prostaglandin residue identity (through R being Formula II residue).
• Choose a heteroatom linker X among O/S/NH.
• Choose a bivalent spacer Y that:
  • can be alkyl/cycloalkyl and can embed further functional handles (including additional ONO2 groups and ester-type nitrooxy substituents T),
  • and in at least some embodiments, connects to or incorporates a heterocycle Y2 with constrained ring size and heteroatom count (N/O/S).

The combined effect is a broad but prostaglandin-anchored nitrooxy prodrug-style family for ocular pressure reduction.

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How Does Claim 2 Narrow the Scope (or Shift It)?

Claim 2 is dependent on Claim 1 and again recites Formula (I) with R, L, X as defined in Claim 1, but refines the definition of Y by changing certain parameter subranges and subcases.

Two main differences visible in your excerpt:

• Y is restricted to certain subfamilies (it reintroduces a) with C1-C20 alkylene and similar optional substitutions, but then it describes Y1 variants differently, with:
  • Y1 is —CH2—CH2— or —CH═CH—(CH2)n2— (as shown in your text)
  • n remains 0 to 20 (in Claim 2 excerpt) but the described subcase structures emphasize particular fragments
• The proviso about ONO2 binding to —(CH2)n1 remains in the same form.

Net: Claim 2 appears to carve out a subset of Claim 1’s Markush space through tightened definitions and restructured Y subcases, rather than changing the overall template of R—X—Y—ONO2.

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What Do Claims 4–6 and 7–9 Do to the Claim Space?

Claim 4: Prostanoid residency restriction

Claim 4 narrows R to:

• travoprost
• unoprostone
• cloprostenol

This is a major scoping constraint because it collapses Claim 1’s generic Formula II residue into a specific set of prostaglandins.

Claim 5: Latanoprost-specific

Claim 5 narrows R to:

• latanoprost

Claim 6: Linker heteroatom restriction

Claim 6 narrows X to:

• —O— or —S— (removes —NH—).

Claim 7–9: Additional Y subfamily restrictions

Claims 7–9 appear to provide progressively narrower embodiments of the Y definition by limiting:

• alkylene length ranges
• integer bounds like n, n1
• and specifying whether X2 is —O— or —S—
• whether R2 is H versus includes CH3
• plus more constraints on:
  • R3 is H or —COCH3
  • whether the ONO2 links are attached under the proviso conditions
  • ring identity class for Y2 in certain embodiments (5- or 6-member heterocycles; and examples given in your excerpt for “for example” classes).

For example:

• Claim 7: Y is bivalent radical with C2-C6 alkylene, optional substitution by —ONO2 or T; and tightened n (0-5) and n1 (1-5).
• Claim 8: a narrower instance with n=0, n1=1, R2=hydrogen.
• Claim 9: a more elaborate Y featuring X1 as —OCO— or —COO—, specified integer ranges n (0-5), n1 (1-5), n2 (0-2) and then sub-parameters n4 (0-3), n5 (1-3) with fixed alkyl substituent constraints (R4-R7 as H in your excerpt) and a defined heterocycle ring class for Y2.

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Which Claim Set Is the Real “Business Scope”? The Combination of Product, Use, and Co-Formulation

Claim 12: medicament use

Claim 12 covers the compounds of any of Claims 1–10 “for use as a medicament.”

Claim 13–17: composition and topical glaucoma treatment

The chain:

• Claim 13: pharmaceutical composition with carrier and effective amount of compound (I) or salt/stereoisomer.
• Claim 14: suitable form for topical administration.
• Claim 15: for treatment of glaucoma and ocular hypertension.
• Claim 16: administered as solution, suspension or emulsion in ophthalmically acceptable vehicle.
• Claim 17: method for treating glaucoma/ocular hypertension by contacting effective intraocular-pressure-reducing amount to the eye.

This creates a layered enforceability path: even if a specific compound design is negotiated around Claim 1 boundaries, use and formulation claims still provide scope if the claimed compound falls within Formula (I).

Claim 18–19: fixed-mixture co-therapy

• Claim 18: composition comprising mixture of compound (I) and one of:
  • a beta-blocker
  • a carbonic anhydrase inhibitor
  • an adrenergic agonist
  • or a nitrooxy derivative.
• Claim 19: specific example mixture with timolol (or nitrooxy derivative thereof).

This is important because ocular glaucoma products are frequently launched as combination drops. The patent supports combination formulations where the prostaglandin-nitrooxy analogue is co-formulated with established MOA agents like timolol.

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What Does Claim 11 Cover? Process Scope and How It Reinforces Product Claims

Claim 11: preparation process for Formula (I)

Claim 11 defines a multi-step process:

1) React compound (III) with:

• (III): where L is defined in Claim 1; P is H or a hydroxylic protecting group; W is —OH, Cl, or —OC(O)R1 where R1 is linear/branched C1-C5 alkyl. 2) Combine with compound (IV) Z-Y-Q, where:
• Y is as defined in Claim 1
• Z is HX or Z1; Z1 is chosen among chlorine, bromine, iodine, mesyl, tosyl
• Q is —ONO2 or Z1 3) If Q is Z1, convert the intermediate to the nitro derivative using:
• a nitrate source 4) Optionally deprotect steps i) or ii).

Landscape effect

Process claims create:

• an additional infringement route for parties manufacturing within the exact synthetic logic, even if they attempt to rephrase or rebrand the final molecule,
• and can narrow design-around options if the same intermediates and nitrate introduction steps are used.

Because the process is tethered to Z-Y-Q where Y matches Claim 1’s Y definitions, manufacturing a non-covered Y may avoid the process claim, while still potentially hitting product claims if the final compound is within Formula (I).

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Claim-to-Structure Enforcement Map (Where a Challenger Would Focus)

Most decisive limitations

1) R prostaglandin residue identity (travoprost/unoprostone/cloprostenol/latanoprost via Claims 4–5). 2) Linker X: O/S versus inclusion of NH (Claim 6 narrows). 3) Y connectivity constraints:

• ONO2 placement proviso (where ONO2 must be bound to —(CH2)n1 for certain Y subfamilies).
• specific classes of bivalent radicals using nested X1/X2/R2 and integer-defined chain lengths. 4) Presence and linkage of Y2:
• Y2 is a heterocycle ring of 5 or 6 members containing N/O/S and tied to the ONO2 linkage described. 5) Ocular use/formulation:
• topical administration and glaucoma/ocular hypertension treatment (Claims 14–17). 6) Combination therapy choice:
• timolol (Claim 19) or class combinations (Claim 18).

Most flexible areas (from the perspective of avoiding literal coverage)

• Varying alkylene length within allowed integer ranges (e.g., n, n1, n2, n3, n4, n5).
• Selecting allowed heteroatoms and substitution types (halogen/hydroxy/—ONO2/T definitions).
• Using salts or stereoisomers is explicitly covered (Claims 1–3 and downstream composition claims).

A challenger would therefore aim to break one of the structural anchors (R identity, ONO2 connectivity/proviso, X heteroatom class, Y2 ring class) rather than attempt to tune chain length.

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US Patent Landscape: How This Patent Likely Fits in Prostaglandin-Nitrooxy/“NO2” Ocular Space

What the patent is trying to own

The claim language and structure indicate ownership of:

• prostaglandin-based ocular agents that carry nitrooxy (ONO2) at the terminus,
• and compositions for:
  • glaucoma
  • ocular hypertension
  • in topical ophthalmic vehicles
• plus combination formulations with:
  • timolol and other standard glaucoma MOA classes.

Where it overlaps with known market MOA

Even without relying on any unstated assumptions, the dependent claims explicitly reference:

• timolol in Claim 19 (beta-blocker co-therapy),
• and list beta-blocker / carbonic anhydrase inhibitor / adrenergic agonist in Claim 18.

This placement aligns the patent with the contemporary glaucoma drug portfolio that uses:

• prostaglandin analogs as base monotherapies,
• and timolol or other MOA agents in combination products.

Enforcement posture likely shaped by claim breadth

• If competitors develop a prostaglandin-nitrooxy analogue where:
  • R matches one of the prostaglandin residues named in Claims 4–5, and
  • X and Y satisfy the ONO2 linkage rules and proviso, then literal product claim exposure is high.
• If competitors switch R to a different prostaglandin scaffold not covered by the named residues, they may still attempt to land outside the dependent claim narrowing, but Claim 1 itself still defines R as prostaglandin residue of Formula (II). That means the core risk remains: the prostaglandin residue class may still be broad unless the Formula (II) mapping is narrow in the specification.

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Key Takeaways

• Claim 1 is a broad Markush family for prostaglandin residue R linked via X (O/S/NH) and a complex bivalent spacer Y to a terminal nitrooxy group (ONO2) under Formula (I).
• Claims 4–6 and 7–9 materially narrow variants using specific prostaglandins (travoprost/unoprostone/cloprostenol or latanoprost), linker selection (O/S), and tighter Y integer ranges and ONO2 placement constraints.
• The patent also owns ocular use and topical formulations for glaucoma/ocular hypertension (Claims 12–17).
• Combination therapy coverage is present, including timolol (Claim 19), supporting enforceability in common co-formulation channels.
• Process Claim 11 provides an additional infringement pathway anchored to reacting prostaglandin-derived intermediates with Z-Y-Q nitro-introduction logic and optional deprotection.

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FAQs

1) Is US 7,273,946 mainly a product patent or also a manufacturing/process patent?
It is both. It includes compound claims (1–10) plus a process claim (11) and downstream medicament/use/composition claims (12–19).

2) What structural element most controls whether a compound falls inside the patent?
The combination of prostaglandin residue R (via Formula II and narrowing dependent claims), the linker X (O/S/NH), and the Y spacer connectivity constraints, especially the proviso on ONO2 binding to —(CH2)n1 for certain Y subcases.

3) Does the patent cover different salt forms and stereoisomers?
Yes. Claim 1 includes pharmaceutically acceptable salts or stereoisomers, and the downstream composition claims track that coverage.

4) What ocular indications are explicitly claimed?
Glaucoma and ocular hypertension, including methods of treating them by contacting an effective intraocular pressure reducing amount to the eye (Claims 15 and 17).

5) Does it cover combination drops with established glaucoma drugs?
Yes. It explicitly covers mixtures with beta-blockers, carbonic anhydrase inhibitors, adrenergic agonists, and nitrooxy derivatives, and it specifically names timolol (Claims 18–19).

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References

[1] US Patent 7,273,946: Claims provided in user prompt (claims 1–19 as quoted).

Drugs Protected by US Patent 7,273,946

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 7,273,946

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	047081
Argentina	098931
Australia	2004313688