Details for Patent: 8,114,890

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Summary for Patent: 8,114,890

Title:	Anti-constipation composition
Abstract:	An object of the present invention is to provide an anti-constipation composition containing a halogenated-bi-cyclic compound as an active ingredient in ratio of bi-cyclic/mono-cyclic structure of at least 1:1. The halogenated-bi-cyclic compound is represented by Formula (I): where X1 and X2 are preferably both fluorine atoms. The composition can be used to treat constipation with out substantive side-effects, such as stomachache.
Inventor(s):	Ryuji Ueno
Assignee:	Sucampo GmbH
Application Number:	US13/274,612
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,114,890
Patent Claim Types: see list of patent claims	Formulation; Compound; Dosage form;

United States Patent 8,114,890: What is claimed for oral liquid formulations stabilizing a bi-cyclic prostaglandin E1 tautomer mix (20:1) and what the patent landscape looks like

Executive summary

• US 8,114,890 claims a liquid oral dosage formulation of 13,14-dihydro-15-keto-16,16-difluoro-prostaglandin E1, where the product contains a bi-cyclic compound (formula I) and a mono-cyclic tautomer (mono-cyclic form of formula I) in a stabilized ratio of at least 20:1.
• The independent claim scope is defined by three pillars: (1) the specific prostaglandin structure and tautomer equilibrium (bi-cyclic vs mono-cyclic), (2) a liquid oral dosage form, and (3) a non-aqueous solvent/suspending agent that stabilizes the tautomer ratio to ≥20:1.
• Dependent claims narrow the solvent system to common pharmaceutics excipients (propylene glycol, PEG, alcohol, polysorbate; plus oils/triglycerides) and narrow dosage form to capsules, including soft capsules.
• Without the full patent text, prosecution history, and family data, the landscape below is necessarily confined to claim-driven scope mapping to identify likely blocking positions for competitors, likely design-around levers, and likely overlapping formulation patent families.

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What is the core claim scope of US 8,114,890 for oral liquid prostaglandin E1 tautomer stabilization?

Featured snippet answer: US 8,114,890 claims an oral liquid dosage form containing a specific bi-cyclic prostaglandin E1 derivative and its mono-cyclic tautomer, where a non-aqueous solvent/suspension agent stabilizes the bi-cyclic:mono-cyclic ratio to at least 20:1.

Independent claim 1: elements and how courts typically read them

Claim 1 requires all of the following:

1. Dosage form type

   • “A liquid dosage form for oral administration.”

2. Actives and chemistry

   • A bi-cyclic compound represented by formula (I).
   • A mono-cyclic tautomer of formula (I).

3. Specific identity

   • The compound is 13,14-dihydro-15-keto-16,16-difluoro-prostaglandin E1.
   • The bi-cyclic and mono-cyclic are the tautomeric forms of the same structural system.

4. Solvent/suspension agent limitation

   • The dosage form uses a non-aqueous solution or suspension agent.

5. Functional stabilization limitation (key scope driver)

   • The non-aqueous solvent/suspending agent “stabilizes” the dosage form such that the ratio of bi-cyclic compound to mono-cyclic tautomer is at least 20:1.

Scope consequence: Even if a competitor uses a different non-aqueous solvent, they can still fall within claim 1 if their formulation meets the ≥20:1 stabilized ratio as required by the functional stabilization element. This makes claim 1 at least partly product-by-condition based on equilibrium outcomes.

What does “stabilizes” mean in claim construction terms?

In formulation patents, “stabilizes” typically means:

• the formulation conditions (solvent/suspending agent) maintain or prevent conversion from bi-cyclic to mono-cyclic over relevant time/conditions; and/or
• the formulation yields a measurable equilibrium ratio at defined test conditions.

Because the claim is framed as a ratio in the dosage form, the infringement question usually becomes measurable: does the accused liquid product exhibit bi-cyclic:mono-cyclic ≥20:1 under the relevant assay conditions described in the patent or typical QC practice.

Why the tautomer ratio is the practical “infringement fulcrum”

• If a competitor’s formulation shifts equilibrium to produce <20:1, it can reduce exposure under claim 1 even if it uses the same prostaglandin derivative.
• If a competitor achieves ≥20:1 using different excipients, it may still infringe even if the excipients are not identical, because claim 1 is anchored to the outcome ratio plus the non-aqueous requirement.

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How do dependent claims 2–5 narrow the solvent system and ratio threshold?

Claim 2: specific non-aqueous solution/suspension agents

Claim 2 limits the non-aqueous agent to one or more of:

• propylene glycol
• polyethylene glycol
• alcohol
• polysorbate

Scope effect: This claim is narrower than claim 1 but stronger evidentiary footing for infringement when those solvents are used.

Claim 3: expanded list including oils/triglycerides

Claim 3 expands to include:

• propylene glycol
• polyethylene glycol
• fatty acid triglyceride
• vegetable oil
• alcohol

Scope effect: This is a broader dependent claim than claim 2 because it explicitly covers common lipid excipients. If a competitor uses triglyceride or vegetable oil as the non-aqueous medium and still stabilizes ≥20:1, it can land within claim 3 (and also claim 1).

Claim 4: additive package

Claim 4 adds that the formulation can further comprise one or more of:

• preservative
• wetting agent
• emulsifier
• dispersant
• anti-oxidant

Scope effect: This claim signals that the patent is not limited to a minimal excipient system. It anticipates typical oral liquid formulation toolkits as long as the system still stabilizes the tautomer ratio.

Claim 5: ratio tightening to ~96:4

Claim 5 requires:

• ratio of bi-cyclic compound to mono-cyclic tautomer is at least about 96:4.

Scope effect: This dependent claim gives patentees an additional infringement “ladder.” A product that meets claim 5 automatically meets claim 1 (since 96:4 is ≥20:1), assuming the “about” construction allows typical assay variability.

Design-around lever: Competitors may attempt to target a ratio between 20:1 and 96:4 to avoid claim 5 while still potentially triggering claim 1. Or they may attempt to drop below 20:1 entirely.

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Does US 8,114,890 cover capsule formats and soft capsules?

Claim 6: liquid dosage form formulated in a capsule

Claim 6 states the liquid dosage form of claim 1 is “formulated in a capsule.”

Scope effect: This ties claim 1’s liquid formulation to a capsule delivery. The claim is not limited to gelatin vs HPMC in the excerpt provided, so capsule material could be broader than a specific polymer type.

Claim 7: soft capsule limitation

Claim 7 narrows to:

• “soft capsule.”

Scope effect: Competitor risk is higher if they offer a soft-gel version of the stabilized tautomer formulation.

Practical reading: A soft capsule containing the stabilized bi-cyclic/mono-cyclic composition in a non-aqueous vehicle can plausibly infringe claims 1–7, provided the ≥20:1 stabilization criterion is met in the product.

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What is the likely patent “infringement map” for competitors?

Below is a claim-driven map of what actions are most likely to create infringement risk, and what levers can reduce it.

Highest infringement risk

1. Using the same active (13,14-dihydro-15-keto-16,16-difluoro-prostaglandin E1) with both tautomeric forms present.
2. Using non-aqueous vehicles that stabilize a ≥20:1 bi-cyclic:mono-cyclic ratio.
3. Using vehicles explicitly enumerated in claims 2 and 3 (propylene glycol, PEG, alcohol, polysorbate, fatty acid triglycerides, vegetable oil).
4. Delivering as a capsule, especially soft capsule, because claims 6–7 add additional structural constraints.

Potential design-around levers

1. Lower the stabilized ratio below 20:1

   • This avoids the functional requirement of claim 1.
   • It is the clearest avoidance strategy if technically feasible, but it may affect stability, solubility, or therapeutic performance.

2. Avoid matching both the “non-aqueous” and “stabilizes to ≥20:1” combination

   • Moving to aqueous systems, mixed solvents, or conditions that permit tautomer conversion can defeat claim 1.

3. Try to remain liquid but change dosage packaging

   • Avoid soft capsules to reduce claim 7 exposure (still potentially covered by claim 6 if it remains in a capsule).
   • Avoid capsule forms to target claims 6–7. However, claim 1 itself is not limited to capsules, so packaging alone may not avoid infringement.

4. Avoid listed solvents

   • Avoiding enumerated excipients reduces exposure to claims 2–3, but claim 1 may still be triggered if the product still achieves ≥20:1 under a different non-aqueous system.

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What likely prior art themes and prosecution arguments matter for claim scope?

Without the full patent record, the following are claim-text driven themes that typically appear in prostaglandin formulation prosecution for tautomer control:

• Stability of tautomer equilibrium
  The patent’s inventive focus is likely the ability of particular non-aqueous media to maintain a predominance of the bi-cyclic tautomer.
• Measuring and defining the ratio
  The “at least 20:1” and “at least about 96:4” ratio constraints suggest the application included assay methods, chromatographic conditions, or stability timepoints defining the ratio.
• Functional language narrowing
  “Stabilizes … in a ratio … at least 20:1” often limits infringement to products that actually exhibit that stabilization outcome, not merely those that contain a solvent that could stabilize under some conditions.

These themes matter in litigation because they shape:

• what “stabilizes” means (measurement conditions and time);
• what counts as the bi-cyclic vs mono-cyclic species; and
• whether an accused product is “equivalent” to the claimed stabilization result.

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How strong is the patent estate around formulation, tautomer ratio, and capsule dosage?

From the claim excerpt alone, the strength profile is:

Potential strengths

• The claims are specific to a particular prostaglandin derivative identity plus tautomer definition.
• Claim 1 includes a measurable functional parameter (≥20:1) that can be tested, which helps with infringement proof and can limit speculative validity arguments.
• Dependent claims add multiple “entry points” (propylene glycol/PEG/polysorbate, oils/triglycerides, soft capsule).

Potential vulnerabilities

• The breadth of claim 1 depends on what constitutes the tautomer ratio in practice:
  • If the patent’s ratio depends on specific assay conditions, claim construction can become narrower.
  • If tautomer equilibrium depends heavily on manufacturing batch conditions, competitors may argue their system does not “stabilize” to the same extent.

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What is the likely competitive landscape by product type (liquid oral vs capsule soft gel)?

Products that are most exposed

• Oral liquids that use non-aqueous vehicles and exhibit a predominance of bi-cyclic species at ≥20:1.
• Soft-gel or gel-caps containing that liquid composition.

Products that can be less exposed

• Oral liquids that do not stabilize bi-cyclic tautomer predominance below 20:1.
• Aqueous or mixed aqueous systems where tautomer distribution changes.
• Non-capsule presentations: tablets or non-liquid forms would not satisfy “liquid dosage form,” absent other claim language.

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Key takeaways

• US 8,114,890 protects a formulation outcome: an oral liquid containing a bi-cyclic prostaglandin PGE1 derivative and its mono-cyclic tautomer, where a non-aqueous solvent/suspending agent stabilizes the bi-cyclic:mono-cyclic ratio to at least 20:1.
• Dependent claims strengthen enforcement leverage through:
  • enumerated non-aqueous vehicles (propylene glycol, PEG, alcohol, polysorbate; triglycerides/vegetable oils),
  • optional standard excipients (preservatives, wetting agents, emulsifiers, dispersants, antioxidants),
  • tighter ratio (about 96:4),
  • capsule delivery, especially soft capsules.
• The primary competitive and design-around pathway is straightforward in claim logic: achieve <20:1 bi-cyclic predominance in the finished product, or avoid the required non-aqueous stabilization outcome.

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FAQs

1. What test method would determine whether a product meets the “bi-cyclic to mono-cyclic” ratio requirement?
2. If a competitor uses a different non-aqueous solvent than those named in claims 2–3, can they still infringe claim 1?
3. Does avoiding soft capsules eliminate infringement risk under US 8,114,890 if the product is still a capsule containing the same stabilized ratio?
4. How would formulation changes during manufacturing (mixing order, temperature, drying) affect the tautomer ratio and claim exposure?
5. Can a product that meets ≥20:1 but not “about 96:4” avoid claim 5 while still infringing claim 1?

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References

1. US Patent 8,114,890. “Liquid dosage form for oral administration comprising 13,14-dihydro-15-keto-16,16-difluoro-prostaglandin E1 bi-cyclic compound and mono-cyclic tautomer stabilized in non-aqueous medium.” (claims excerpt provided by user).

Drugs Protected by US Patent 8,114,890

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 8,114,890

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	1315485		C01315485/01	Switzerland
European Patent Office	1315485		C300757	Netherlands
European Patent Office	1315485		49/2015	Austria
European Patent Office	1315485		2015/028	Ireland
European Patent Office	1315485		122015000080	Germany