United States Patent 5,434,171: Claim Scope, Exclusivity, and Patent Landscape

U.S. Patent No. 5,434,171 is a product, solid-state, therapeutic-use, formulation, and manufacturing-process patent. Its core protection is directed to crystalline forms of a substituted piperidine compound, including hydrochloride-acetone solvates, malate salts, sesquimalate salts, and a crystalline dihydrate. The patent also claims use against peripheral opioid receptors, treatment of gastrointestinal disorders, pharmaceutical formulations, and crystallization of a monohydrate.

The patent issued on July 18, 1995. Based on the pre-Uruguay Round patent-term rule generally applicable to applications filed before June 8, 1995, its base term was 17 years from issuance, producing a nominal expiration date of July 18, 2012. Any patent-term extension, terminal disclaimer, or pediatric extension must be confirmed from the USPTO and FDA records before being used in a current freedom-to-operate opinion.

What does U.S. Patent 5,434,171 protect?

The patent protects defined crystalline compounds and pharmaceutical uses rather than every compound having the disclosed piperidine pharmacophore.

Claim group	Subject matter	Protection type
Claims 1-7	Crystalline salts and solvates of Formula 20	Product and solid-state protection
Claims 8-9	Crystalline dihydrate of Formula 5	Product and hydrate protection
Claims 10-13	Peripheral opioid-receptor binding and gastrointestinal treatment	Method-of-use protection
Claims 14-16	Pharmaceutical formulations, including hard gelatin capsules	Formulation protection
Claim 17	Preparation of crystalline monohydrate from approximately 50:50 methanol/water	Manufacturing-process protection

The patent is therefore broader than a single crystal-form claim, but its practical scope depends heavily on the identity of the structures shown in the missing Formula 20, Formula 5, and Formula 3 drawings. The textual claims identify the relevant salts, solvates, stereochemistry, and therapeutic applications, but the omitted structures prevent a complete Markush-structure analysis.

How broad is claim 1 of U.S. Patent 5,434,171?

Claim 1 is the principal product claim. It covers a crystalline compound of Formula 20 in which:

R1 is a C1-C6 alkyl group;
the counterion or associated salt is hydrochloride, malate, or sesquimalate;
the hydrochloride form is solvated with one molecule of acetone per molecule of active compound; and
the sesquimalate contains three malate molecules associated with two molecules of the Formula 20 compound.

The claim combines chemical identity with solid-state attributes. A product must satisfy both elements. A liquid, amorphous solid, different polymorph, or different solvate would not necessarily fall within claim 1 even if it contained the same active moiety.

The R1 limitation creates a six-carbon alkyl Markush scope. It can cover methyl, ethyl, propyl, butyl, pentyl, and hexyl variants, subject to the exact structural position of R1 in Formula 20. Claims 4-7 narrow the generic scope to a defined stereochemical compound and specified salts.

The hydrochloride limitation is unusually specific. It requires an acetone monosolvate. A hydrochloride without acetone, a hydrochloride with a different solvent, or a hydrate may avoid literal infringement if the product does not meet the claim's solvation requirement.

What do claims 2 through 7 add?

Claims 2 and 3 narrow claim 1 by selecting hydrochloride and sesquimalate, respectively.

Claim 4 identifies a particular stereochemical compound:

(2S,3R,4R)[[2-[[4-(3-hydroxyphenyl)-3,4-dimethyl-1-piperidinyl]methyl]-1-oxo-3-phenylpropyl]amino]acetic acid 2-methylpropyl ester.

Claims 5-7 then specify the solid forms of that compound:

Claim 5 covers the hydrochloride acetone monosolvate.
Claim 6 covers the sesquimalate.
Claim 7 covers the malate.

These dependent claims are commercially important because they reduce uncertainty over the active chemical species and identify specific salt forms that could be used in development or manufacturing.

The claim language also raises a drafting issue. Claim 4 refers to “Formula 1,” while claim 1 refers to “Formula 20.” That may reflect patent text conversion or numbering from the issued document. The original patent drawings and prosecution history control the meaning of those references.

What do claims 8 and 9 protect?

Claims 8 and 9 protect a crystalline dihydrate of Formula 5. Claim 9 requires the material to be at least 97% of the specified (2S,3R,4R) dihydrate.

This is a purity-limited solid-state claim. It can be infringed by a batch containing the claimed dihydrate at or above the 97% threshold, assuming the Formula 5 structure and analytical test method are satisfied. The claim is narrower than a claim covering any hydrate because it requires:

crystallinity;
the specific Formula 5 compound;
the dihydrate stoichiometry; and
at least 97% of the specified stereochemical dihydrate.

A competitor using an anhydrous form, monohydrate, amorphous material, racemate, or a different stereoisomer would present a different infringement analysis.

What therapeutic uses are covered by claims 10 through 13?

Claims 10 and 11 cover administering the claimed compound to bind a peripheral opioid receptor in a patient. Claims 12 and 13 cover treatment of:

irritable bowel syndrome;
idiopathic constipation; and
non-ulcer dyspepsia.

The method claims require administration of an effective amount. They do not simply cover possession or manufacture of the compound. In an ANDA context, infringement risk would generally depend on the proposed labeling, product composition, manufacturing activity, and the scope of any Orange Book-listed use code.

Claims 12 and 13 are narrower than claims 10 and 11 because they require one of the listed gastrointestinal conditions. A use for another peripheral opioid-receptor-mediated condition may fall within claim 10 or 11 but outside claims 12 and 13.

What formulation protection does the patent provide?

Claims 14 and 15 cover pharmaceutical formulations containing an effective amount of either the claim 1 compound or the claim 8 dihydrate with one or more pharmaceutically acceptable excipients.

Claim 16 narrows claim 15 to a hard gelatin capsule.

The formulation claims do not require a particular excipient, dosage strength, dissolution profile, or release mechanism. Their breadth depends on the meaning of “effective amount” and the structural identity of the active compound. The hard gelatin capsule claim is comparatively narrow and may be avoided by a tablet, softgel, liquid, coated multiparticulate, or other dosage form if the remaining claims are not implicated.

A generic manufacturer could face separate risks for:

using the patented crystalline active ingredient;
reproducing the claimed dihydrate;
adopting the claimed capsule formulation; and
using a patented manufacturing route.

Avoiding claim 16 would not avoid claims 14 or 15.

What does claim 17 protect about manufacturing?

Claim 17 covers a process for preparing a crystalline monohydrate of Formula 3 by crystallization from a solvent containing approximately 50% methanol and 50% water by weight.

The claim has process limitations that include:

the target crystalline monohydrate;
crystallization as the operative step;
a solvent system of approximately equal parts methanol and water; and
the specified Formula 3 compound.

A process using ethanol and water, acetone and water, a substantially different methanol concentration, spray drying, precipitation without crystallization, or a different isolation route may avoid literal infringement. The doctrine of equivalents could still be relevant if the substitute process performs substantially the same function in substantially the same way, but the solvent ratio is a meaningful limitation.

Claim 17 is particularly relevant to API suppliers because process claims can create infringement exposure even when the final dosage form is outside a formulation claim.

When did U.S. Patent 5,434,171 lose exclusivity?

The patent issued July 18, 1995, and its apparent base term expired July 18, 2012 under the 17-year-from-issue rule applicable to the filing period. The patent was therefore not expected to provide ordinary U.S. patent exclusivity after that date unless an extension applied.

Milestone	Date or status
U.S. patent application	Filed before June 8, 1995
Patent issuance	July 18, 1995
Base term	17 years from issuance
Nominal base expiration	July 18, 2012
FDA approval of Entereg	May 29, 2008
NCE exclusivity	Five years from approval, subject to applicable regulatory rules
Current patent relevance	Historical patent estate; current enforceability requires live USPTO/FDA confirmation

FDA approval of the marketed product would not, by itself, extend the patent. Patent-term extension under 35 U.S.C. § 156 is separate from FDA regulatory exclusivity and applies only if the statutory requirements were met and the extension was granted.

What is the Orange Book status of the patent?

The compound associated with these claims was commercialized as Entereg, whose active ingredient is alvimopan. Entereg was approved by the FDA in 2008 for reducing postoperative ileus following bowel resection with primary anastomosis. The approved indication is narrower than the gastrointestinal indications recited in claims 12 and 13.

Historical Orange Book listings should be reviewed for:

U.S. Patent No. 5,434,171;
the listed expiration date;
any use code;
any pediatric-exclusivity notation; and
any later patents covering formulation, dosage, or use.

The FDA-approved labeling is relevant because the patent claims and the approved indication do not align perfectly. Claims 12 and 13 recite irritable bowel syndrome, idiopathic constipation, and non-ulcer dyspepsia, while the approved Entereg label addresses postoperative ileus. A generic applicant would analyze both the Orange Book-listed patents and any applicable section viii carve-out.

Were there Paragraph IV challenges or generic litigation?

A Paragraph IV certification would challenge an Orange Book-listed patent as invalid, unenforceable, or not infringed. The supplied record does not establish a specific Paragraph IV filing, ANDA number, district-court case, or settlement involving U.S. Patent 5,434,171.

The commercial risk profile is different from a typical high-volume chronic drug. Entereg is used under a restricted hospital program and is administered for a limited postoperative period. That limits the addressable generic market and may reduce the commercial incentive for an early Paragraph IV challenge, even where the patent term is approaching expiration.

No conclusion about a particular generic challenger, settlement agreement, or litigation outcome should be drawn from the claim text alone.

How does the patent compare with a conventional small-molecule product patent?

Issue	U.S. Patent 5,434,171	Typical small-molecule composition patent
Core protection	Crystalline salts, solvates, hydrates	Broad active chemical entity
Solid-state scope	Extensive	Often absent or secondary
Use claims	Peripheral opioid receptor and gastrointestinal conditions	Usually one or more approved indications
Formulation claims	Broad excipient formulation plus hard gelatin capsule	May cover release profile or dosage strength
Process claims	Specific methanol/water crystallization	Often synthetic intermediates or reaction steps
Design-around potential	Relatively high for salts, solvates, and processes	Lower if broad molecule claim remains valid
Biosimilar pathway	Not applicable	Not applicable
Generic pathway	ANDA	ANDA

The patent estate is stronger against a product that reproduces the claimed crystalline form, salt, hydrate, or capsule. It is weaker against a competitor that uses a chemically and physically distinct solid form and an independent manufacturing route.

What generic entry risks exist?

Product risk

A generic using the same active crystalline form could face infringement allegations under claims 1, 4-9, or 14-16. Solid-state characterization would likely involve powder X-ray diffraction, differential scanning calorimetry, thermogravimetric analysis, water or solvent content, optical rotation, and chiral purity.

Use risk

An ANDA applicant could seek a label directed only to the FDA-approved postoperative ileus indication. That may reduce exposure to claims 12 and 13 if the patented indications are not approved or listed in the Orange Book. Claims 10 and 11 could remain relevant if the label expressly describes peripheral opioid-receptor binding.

Process risk

An API manufacturer using the claimed methanol/water crystallization route could face process-claim exposure even if the applicant changes the capsule composition.

Commercial risk

The restricted Entereg distribution model, short treatment duration, and hospital-focused indication reduce expected generic revenue compared with a chronic outpatient gastrointestinal drug. The likely value of the patent estate is therefore concentrated in hospital formulary access, supply contracts, and manufacturing economics rather than broad retail substitution.

Does biosimilar risk apply?

No. The claimed compounds are chemically synthesized small molecules. The relevant regulatory pathway is an ANDA under section 505(j) of the Federal Food, Drug, and Cosmetic Act, not a biosimilar application under section 351(k) of the Public Health Service Act.

The principal competitive issues are generic equivalence, solid-form selection, labeling, and API manufacturing. Biosimilar interchangeability, reference-product exclusivity, and biologic comparability are not relevant to these claims.

How strong is the patent estate?

The patent has moderate historical strength as a solid-state and formulation patent, but it is materially narrower than a broad composition-of-matter patent.

Its strongest features are:

multiple crystalline forms;
defined counterions and stoichiometries;
an acetone monosolvate limitation;
stereochemically defined species;
a quantified 97% dihydrate limitation; and
a manufacturing claim directed to a practical crystallization process.

Its principal weaknesses are:

dependence on specific solid forms;
potential design-around through alternative salts, hydrates, polymorphs, or amorphous forms;
uncertainty created by omitted structural formulas;
possible claim-construction disputes over solvation and crystallinity; and
expiration of the base patent term.

Key Takeaways

U.S. Patent 5,434,171 is not limited to one pharmaceutical use. It covers crystalline compounds, salts, solvates, hydrates, therapeutic methods, formulations, and a crystallization process.
Claims 1-9 are the principal product and solid-state claims.
Claims 10-13 cover peripheral opioid-receptor binding and specified gastrointestinal conditions.
Claims 14-16 cover formulations, including hard gelatin capsules.
Claim 17 covers preparation of a crystalline monohydrate using approximately 50% methanol and 50% water.
The patent issued July 18, 1995, with a nominal 17-year base term ending July 18, 2012.
The patent is associated with the alvimopan product Entereg, but the supplied claim text does not establish current Orange Book listing status, a patent-term extension, a Paragraph IV filing, or a settlement.
Generic risk is highest when the proposed product reproduces the claimed crystal form, hydrate, salt, capsule formulation, or methanol/water crystallization route.
Biosimilar risk does not apply because the product is a chemically synthesized small molecule.

FAQs About U.S. Patent 5,434,171

Is U.S. Patent 5,434,171 a composition-of-matter patent?

It is a composition patent for defined crystalline forms and associated salts, solvates, and hydrates. The supplied claims do not establish a broad claim to every form of the underlying active molecule.

Can a generic avoid the patent by using a different salt?

Potentially. A different salt may avoid claims limited to hydrochloride, malate, or sesquimalate, but the result depends on the scope of claim 1, the omitted structures, and any other enforceable patent claims.

Does a different capsule excipient avoid claim 16?

Not necessarily. Claim 16 is directed to a hard gelatin capsule containing the claim 8 formulation. Changing excipients may not avoid infringement if the active compound, dihydrate, and capsule limitations remain satisfied.

Can a manufacturer avoid claim 17 by changing the solvent ratio?

A materially different methanol/water ratio may avoid literal infringement, but the precise result depends on claim construction and possible equivalence arguments.

Does FDA approval create patent protection for the gastrointestinal indications in claims 12 and 13?

No. FDA approval and patent rights are separate. The scope of the patent claims, Orange Book listings, regulatory exclusivity, and approved labeling must be analyzed independently.

References

U.S. Patent and Trademark Office. (1995). U.S. Patent No. 5,434,171.
U.S. Food and Drug Administration. (2008). Entereg (alvimopan) prescribing information.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations.
U.S. Food and Drug Administration. (2008). Drugs@FDA: Entereg application materials.
U.S. Congress. (1984). Drug Price Competition and Patent Term Restoration Act of 1984, Pub. L. No. 98-417.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	200279	⤷ Start Trial
Australia	681198	⤷ Start Trial
Australia	7917094	⤷ Start Trial
Brazil	9404842	⤷ Start Trial
Canada	2137221	⤷ Start Trial
China	1057294	⤷ Start Trial
China	1111239	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 5,434,171

Summary for Patent: 5,434,171