United States Patent 5,914,131: Claim Scope, Hydromorphone Patent Estate, and Generic Entry Risk

U.S. Patent No. 5,914,131 protected an osmotic, extended-release hydromorphone dosage form associated with the OROS delivery platform. Its claims covered multilayer tablets with a hydromorphone drug layer, expandable osmotic layer, semipermeable cellulose acetate membrane, and delivery orifice. The patent also covered specified hydromorphone release profiles and oral treatment methods.

The patent issued June 22, 1999, from an application filed March 13, 1997. Its 20-year patent term expired in March 2017, subject to any applicable patent-term adjustment or extension. It therefore does not present a current U.S. patent barrier to generic hydromorphone extended-release products. The commercial relevance of the patent was greatest during development and launch of Exalgo, an extended-release hydromorphone hydrochloride tablet.

What does U.S. Patent 5,914,131 protect?

The patent protects a controlled-release osmotic dosage form rather than hydromorphone as a molecule. The core architecture is:

A drug layer containing hydromorphone or a pharmaceutically acceptable salt.
An expandable or delivery layer containing high-molecular-weight poly(ethylene oxide), sodium chloride or another osmagent, and hydroxypropylmethylcellulose.
A semipermeable cellulose acetate membrane containing polyethylene glycol.
One or more passages or exits through the membrane.
Osmotically controlled delivery over an extended period.

The claims identify hydromorphone hydrochloride, poly(ethylene oxide) with molecular weights of approximately 200,000 and 2,000,000, polyvinylpyrrolidone, sodium chloride, hydroxypropylmethylcellulose, cellulose acetate, polyethylene glycol, lubricants, antioxidants and colorants.

The patent has two principal claim groups:

Claim group	Subject matter	Principal limitations
Claims 1-4	Specific dosage-form embodiments	Exact ingredient quantities, membrane composition, release rate and release duration
Claims 5-43	Formulation and dosage-form species	Ingredient percentages, layer weights, dose strengths, excipients and membrane parameters
Claims 44-46	Delivery-pattern and treatment claims	Dose range, 24-hour release pattern, plasma concentration and oral administration

The claims are formulation and device claims. They do not broadly claim all extended-release hydromorphone products.

How do claims 1 through 4 define the protected formulations?

Claims 1 through 4 are highly specific composition-performance claims. Each requires the claimed hydromorphone amount, excipient quantities, multilayer construction, membrane composition, passageway and release behavior.

Claim	Hydromorphone amount	Stated release rate	Stated release duration
1	8 mg	0.427 mg/hour	17.3 hours
2	32 mg	1.811 mg/hour	16.1 hours
3	64 mg	3.77 mg/hour	15.3 hours
4	16 mg	0.957 mg/hour	15.0 hours

These claims have several cumulative limitations:

A defined drug-layer composition.
A separate delivery or expandable layer.
A specified semipermeable wall.
A passageway in the wall.
A controlled release rate over a stated period.

A competing product would generally need to satisfy every limitation of an asserted claim for literal infringement. A product with the same hydromorphone strength but a different release mechanism, membrane, excipient system or release profile would not automatically infringe.

The claims are particularly vulnerable to noninfringement based on formulation differences because they identify ingredient weights and molecular weights with substantial precision. Claims 1-4 are narrower than the percentage-based claims that follow.

What formulations are protected by claims 5 through 43?

Claims 5 through 43 cover formulation families corresponding to 8 mg, 16 mg, 32 mg, 64 mg and higher hydromorphone strengths. The claims use percentage ranges and dependent limitations to define drug-layer and expandable-layer compositions.

8 mg and 16 mg dosage forms

Claim 5 covers a drug layer containing:

8 mg hydromorphone or a pharmaceutically acceptable salt;
84.70 wt% poly(ethylene oxide);
5 wt% polyvinylpyrrolidone;
0.05 wt% butylated hydroxytoluene; and
0.25 wt% magnesium stearate.

The expandable layer contains:

63.675 wt% poly(ethylene oxide);
30 wt% sodium chloride;
5 wt% hydroxypropylmethylcellulose;
0.075 wt% butylated hydroxytoluene;
1 wt% colorant; and
0.25 wt% magnesium stearate.

Claims 6-12 narrow this formulation to a 16 mg dose, specified layer weights and a 10 wt% hydromorphone concentration in the drug layer.

The drug layer and expandable layer are enclosed in a membrane containing 99 wt% cellulose acetate and 1 wt% polyethylene glycol. The exit in the membrane permits delivery of hydromorphone.

32 mg dosage form

Claim 13 covers a 32 mg hydromorphone dosage form with a drug layer containing 74.75 wt% poly(ethylene oxide), 5 wt% polyvinylpyrrolidone and 0.25 wt% magnesium stearate. Claim 16 specifies that hydromorphone represents 20 wt% of the drug layer.

Claims 14 and 15 add layer-weight limitations:

Drug layer: 160 mg.
Expandable layer: 120 mg.

64 mg dosage form

Claim 17 covers a 64 mg oral hydromorphone formulation. The drug layer contains 64.75 mg of a poly(alkylene oxide), 5 wt% polyvinylpyrrolidone and 0.25 wt% lubricant. The expandable layer contains poly(alkylene oxide), an osmotically effective solute, hydroxypropylalkylcellulose, antioxidant, colorant and lubricant.

Claims 18-20 narrow the formulation through:

Drug-layer weight of 214 mg.
Expandable-layer weight of 164 mg.
Hydromorphone concentration of 30 wt% of the drug layer.

Commercial-strength formulation families

Claims 21-43 provide detailed formulations for drug-layer weights of approximately 80 mg, 152.4 mg, 160 mg and 213.3 mg. These correspond to different hydromorphone dose levels and include hydromorphone hydrochloride at approximately 10.5%, 20% or 30%.

Key limitations include:

Parameter	Claimed range or value
Drug-layer poly(ethylene oxide)	Approximately 200,000 molecular weight
Expandable-layer poly(ethylene oxide)	Approximately 2,000,000 molecular weight
Polyvinylpyrrolidone	Approximately 38,000-42,000 molecular weight
Hydroxypropylmethylcellulose	Approximately 9,200-11,300 molecular weight
Cellulose acetate acetyl content	Approximately 39.8%
Polyethylene glycol	Approximately 3,350-4,000 molecular weight
Membrane composition	99 wt% cellulose acetate and 1 wt% polyethylene glycol
Colorant	Black iron oxide and lactose, including a 95:5 mixture
Drug-layer antioxidant	Butylated hydroxytoluene
Expandable-layer osmagent	Usually sodium chloride

Claims 21-43 are more commercially relevant than claims 1-4 because they describe formulation families rather than only one exact tablet composition. They remain constrained, however, by the required two-layer osmotic structure and membrane system.

What do claims 44 through 46 cover?

Claims 44 through 46 shift from physical formulation limitations to pharmacokinetic and therapeutic delivery limitations.

Claim 44: extended-release delivery pattern

Claim 44 covers a formulation containing 1 mg to 500 mg of hydromorphone or a pharmaceutically acceptable salt in a pharmaceutically acceptable carrier that delivers:

0% to 20% of the dose within 0 to 4 hours;
20% to 50% within 0 to 8 hours;
55% to 85% within 0 to 14 hours; and
80% to 100% within 0 to 24 hours.

The claim is broader in ingredient detail than claims 21-43 because it does not recite the full cellulose acetate, poly(ethylene oxide) and osmagent composition. Its scope depends on proving that the accused formulation meets the delivery pattern.

Claim 45: method of hydromorphone therapy

Claim 45 requires oral administration of the extended-release formulation to produce:

A first plasma hydromorphone concentration;
A second elevated plasma concentration; and
A third continuous plasma concentration.

The method is directed to hydromorphone therapy lasting up to 24 hours.

Claim 46: plasma concentration method

Claim 46 requires oral administration into the gastrointestinal tract and production of a plasma hydromorphone concentration greater than zero and up to 25 ng/mL for up to 24 hours.

These claims create evidentiary issues in litigation. Infringement would ordinarily require pharmacokinetic testing, validated release testing, product composition evidence or an applicable regulatory submission. A generic label alone may not establish that the product meets the claimed plasma profile.

When did U.S. Patent 5,914,131 expire?

The patent issued from a March 13, 1997 application. Under the post-URAA patent-term framework, the ordinary term was 20 years from the earliest effective nonprovisional filing date. The ordinary expiration date was therefore March 13, 2017, assuming no patent-term adjustment or extension altered the calculation (U.S. Patent and Trademark Office, n.d.-a).

Event	Date
Earliest relevant nonprovisional filing	March 13, 1997
Patent issued	June 22, 1999
Ordinary 20-year expiration	March 13, 2017
Current status	Expired

Patent expiration ends the right to exclude others from practicing the claimed invention in the United States. It does not eliminate other patents that may have covered a particular commercial product, manufacturing process, abuse-deterrent feature or later formulation.

What was the FDA and Orange Book status of the hydromorphone product?

FDA approved Exalgo extended-release tablets on April 1, 2010, for management of pain in opioid-tolerant patients severe enough to require daily, around-the-clock, long-term opioid treatment (FDA, 2010a). The product contained hydromorphone hydrochloride and used an extended-release osmotic delivery system.

The Exalgo label identified strengths including 8 mg, 12 mg, 16 mg, 32 mg and 64 mg. The product was subject to controlled-substance requirements and had a boxed warning concerning respiratory depression, misuse, abuse, addiction and overdose (FDA, 2010b).

The Orange Book is the relevant FDA source for listed patents and regulatory exclusivity. Patent 5,914,131 was associated with the Exalgo hydromorphone extended-release product during the period when the patent remained in force. The patent did not protect immediate-release hydromorphone tablets, injectable hydromorphone or all hydromorphone formulations.

Hydromorphone is an established active ingredient. The commercial regulatory protection for Exalgo therefore depended primarily on formulation-related FDA exclusivity and patents rather than new chemical entity exclusivity. The likely three-year exclusivity period associated with approval of a new dosage form would have been materially shorter than the patent term and would not have extended beyond the patent’s 2017 expiration.

Which companies challenged the Exalgo patent estate?

The relevant generic pathway was an ANDA supported by Paragraph IV certifications against listed patents. Paragraph IV litigation allows an ANDA applicant to assert that a listed patent is invalid, unenforceable or not infringed. The filing of the certification can trigger litigation under 21 U.S.C. § 355(j)(5)(B)(iii).

Publicly reported generic activity involved major ANDA applicants seeking approval for hydromorphone hydrochloride extended-release tablets, including Actavis-related entities. The commercial effect of any challenge depended on:

The specific Orange Book-listed patent;
The ANDA applicant’s proposed formulation;
Whether the applicant certified Paragraph IV or waited for patent expiry;
Whether the NDA holder filed suit within the statutory period;
Whether a 30-month stay applied; and
Whether the parties entered a settlement or authorized early entry.

Because Patent 5,914,131 expired in 2017, a current Paragraph IV challenge to that patent would have no meaningful ability to block launch. A historical challenge could still have affected launch timing before expiration, particularly if other listed patents remained in force.

What patent litigation and settlement issues affected generic launch?

For a product such as Exalgo, the principal litigation issues would have been:

Literal infringement

A generic product would be assessed against the exact limitations of the asserted claims. Relevant differences could include:

Alternative osmotic agents;
Different poly(ethylene oxide) grades;
Different membrane thickness or composition;
Different molecular-weight ranges;
A non-OROS release mechanism;
A different orifice configuration; or
A release profile outside the claimed pattern.

Validity

Potential validity issues include:

Anticipation by earlier osmotic delivery patents;
Obviousness based on OROS platform patents combined with hydromorphone formulation knowledge;
Written-description and enablement challenges to broad claims 44-46;
Indefiniteness of release-pattern or plasma-concentration limitations; and
Lack of objective boundaries for terms such as “continuous plasma hydromorphone concentration.”

Settlement

A settlement could have permitted an agreed generic entry date before patent expiration or after expiration. Settlement analysis would require the actual agreement, court docket and FDA approval status. The expiration of Patent 5,914,131 means that any historical settlement no longer preserves an enforceable exclusion right under this patent.

How strong is the patent estate for hydromorphone osmotic delivery?

Patent 5,914,131 was strongest against a product that copied the complete OROS design and one of the disclosed hydromorphone strengths. Its strongest claim features were:

The two-layer tablet architecture;
The semipermeable cellulose acetate membrane;
The defined poly(ethylene oxide) molecular weights;
The hydromorphone hydrochloride drug-layer percentages;
The membrane polymer ratio; and
The combination of composition and release behavior.

Its weaker features were:

The broad 1 mg to 500 mg delivery range in claim 44;
The functional plasma-concentration language in claim 46;
The lack of a single universal release mechanism in claims 44-46; and
Dependence on proving in vivo or in vitro performance.

The estate’s present strength is zero as an exclusion right because the patent has expired. Its residual value is technical and historical. The patent can still identify formulation design choices, prior-art disclosures and possible prosecution-history arguments in later patent disputes.

How does this patent compare with generic hydromorphone entry risks?

Product type	Risk from Patent 5,914,131
Immediate-release hydromorphone tablet	None from this patent
Hydromorphone injection	None from this patent
Non-osmotic extended-release tablet	Low, subject to claim 44-46 analysis
OROS-style two-layer tablet	Historically high; currently none because the patent expired
Product with different membrane polymer	Historically reduced literal-infringement risk
Product with similar PK profile but different formulation	Possible historical risk under claims 44-46
Current generic extended-release hydromorphone product	No current blocking risk from this patent

No biosimilar pathway applies. Hydromorphone is a small-molecule active ingredient, so competitors use the ANDA pathway rather than a biosimilar application under the Public Health Service Act.

What manufacturing and geographic barriers did the patent create?

The patent applied in the United States only. It did not itself create rights in Europe, Canada, Japan or other jurisdictions. Foreign counterparts would need separate examination and maintenance, and their claim scope and expiration dates could differ.

Manufacturing barriers included:

Bilayer compression;
Consistent drug-layer and expandable-layer weights;
Application of a uniform semipermeable membrane;
Formation of a calibrated exit orifice;
Control of poly(ethylene oxide) hydration and swelling;
Reproducible osmotic release; and
Validation of release performance over the claimed period.

These manufacturing constraints could raise development cost even after patent expiration. They do not, however, create patent exclusivity independently of an unexpired patent or regulatory exclusivity.

Key Takeaways

U.S. Patent 5,914,131 protected an osmotic, multilayer extended-release hydromorphone dosage form.
Claims 1-4 are narrow claims directed to exact compositions and release rates.
Claims 5-43 cover specified hydromorphone dosage-form families, layer weights and excipient percentages.
Claims 44-46 cover broader release-pattern, plasma-concentration and treatment methods.
The patent issued June 22, 1999, and ordinarily expired March 13, 2017.
It was commercially relevant to Exalgo, FDA-approved in 2010.
No current generic or biosimilar launch is blocked by this expired patent.
Historical Paragraph IV litigation risk was greatest for generic products copying the OROS multilayer architecture.
The patent did not cover immediate-release hydromorphone, injectable hydromorphone or hydromorphone as a chemical compound.
Current competitive risk must be assessed against later Exalgo-related patents, product-specific Orange Book listings and regulatory status, not Patent 5,914,131 alone.

FAQs About U.S. Patent 5,914,131

Does Patent 5,914,131 cover all extended-release hydromorphone tablets?

No. It covers specific osmotic dosage forms, defined compositions and certain delivery profiles. A different extended-release technology may fall outside the claims.

Is Patent 5,914,131 still enforceable against a hydromorphone generic?

No. The patent’s ordinary U.S. term expired in March 2017.

Does the patent cover hydromorphone hydrochloride as an active ingredient?

It covers dosage forms containing hydromorphone or a pharmaceutically acceptable salt, including hydromorphone hydrochloride. It does not claim hydromorphone hydrochloride as a new chemical entity.

Does a generic product need to reproduce the claimed OROS tablet to infringe?

For the formulation claims, a product generally must contain each required claimed element for literal infringement. A non-OROS product with a materially different structure may avoid those claims, although historical method or performance claims required separate analysis.

Are biosimilars relevant to Exalgo or Patent 5,914,131?

No. Exalgo contains the small-molecule opioid hydromorphone hydrochloride. Generic competition proceeds through the ANDA pathway, not the biosimilar pathway.

References

Food and Drug Administration. (2010a). FDA approves new treatment for opioid-tolerant patients with chronic pain. U.S. Department of Health and Human Services.
Food and Drug Administration. (2010b). Exalgo (hydromorphone hydrochloride) extended-release tablets prescribing information. U.S. Department of Health and Human Services.
Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations: Orange Book. U.S. Department of Health and Human Services.
U.S. Patent and Trademark Office. (1999). Osmotic dosage form comprising hydromorphone, U.S. Patent No. 5,914,131.
U.S. Patent and Trademark Office. (n.d.-a). Patent term calculator. U.S. Department of Commerce.
United States Code. (2023). 21 U.S.C. § 355: New drugs. Cornell Legal Information Institute.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	227575	⤷ Start Trial
Austria	230992	⤷ Start Trial
Australia	2908395	⤷ Start Trial
Australia	693910	⤷ Start Trial
Canada	2188451	⤷ Start Trial
Germany	69528852	⤷ Start Trial
Germany	69529412	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 5,914,131

Summary for Patent: 5,914,131