United States Drug Patent 5,004,613: Claims, Scope, Expiration, and Patent Landscape

U.S. Patent No. 5,004,613 protected sustained-release pharmaceutical tablets made with hydroxyethyl cellulose, povidone, a wicking agent, and an erosion promoter. Its claims covered manufacturing processes, single-layer matrix tablets, immediate-release/sustained-release bilayer tablets, and products made by the claimed processes. The patent issued on April 2, 1991, and its 17-year statutory term expired on April 2, 2008, absent a patent-term extension. It therefore presents no current U.S. patent barrier to generic or competing sustained-release products.[1][2]

The patent’s commercial value was concentrated in low-excipient, high-active-load matrix tablets, particularly acetaminophen bilayer tablets. The core formulation requires active pharmaceutical ingredient at approximately 68% to 94% by weight and total excipients generally above 6% but below 32% of the finished composition.

What does U.S. Patent 5,004,613 protect?

The patent protects two related technical concepts:

A wet-granulation process for making a sustained-release tablet.
A compressed sustained-release matrix containing a defined combination of excipients.

The formulation uses hydroxyethyl cellulose as the primary release-controlling polymer. Povidone acts as the granulating binder. Microcrystalline cellulose or another wicking agent promotes liquid penetration into the matrix. Starch or a superdisintegrant acts as an erosion promoter.

The claimed architecture is different from a conventional high-polymer sustained-release tablet. The active ingredient forms most of the tablet by weight, while the excipient system controls water penetration, matrix erosion, and drug release.

Core formulation elements

Component	Claimed range or function
Pharmaceutical active	About 68% to 94% by weight in process claims
Hydroxyethyl cellulose	5 to 25 parts by weight
Povidone	5 to 25 parts by weight
Wicking agent	5 to 25 parts in initial blend; 5 to 45 parts in final blend
Total wicking agent in composition claims	10 to 70 parts
Erosion promoter	1 to 15 parts
Pregelatinized starch	2 to 15 parts in narrower claims
Sodium starch glycolate, croscarmellose sodium, or crospovidone	1 to 10 parts
Lubricant	0 to 10 parts
Glidant	0 to 5 parts
Total excipients and granulating agent	More than 6% and less than 32%; narrower claims require less than 15%

The claims are expressed largely as parts by weight of the total composition or sustained-release layer. That drafting approach makes the relative concentration of each excipient central to claim scope.

How many independent claims does Patent 5,004,613 have?

The patent has five principal independent claim groups: claims 1, 6, 13, 14, and 18. Claims 19 and 20 are product-by-process claims dependent on the process claims.

Claim	Claim type	Principal subject matter
1	Independent process	Single-layer sustained-release tablet made by wet granulation
6	Independent composition	Sustained-release matrix tablet with hydroxyethyl cellulose, povidone, wicking agent, and erosion promoter
13	Independent process	Immediate-release/sustained-release bilayer tablet
14	Independent composition	Bilayer tablet, expressly referring to acetaminophen in the sustained-release layer
18	Independent product/process combination	Bilayer tablet using specified excipient ranges and processing steps
19	Product-by-process	Product made by the process of claim 1
20	Product-by-process	Product made by the process of claim 14

Claims 2 through 5 narrow claim 1. Claims 7 through 12 narrow claim 6. Claims 15 through 17 narrow claim 14.

What process is required by claim 1?

Claim 1 requires every material process step below:

Dissolve 5% to 25% povidone in water or an alcohol-water mixture.
Dry blend the active ingredient, 5% to 25% hydroxyethyl cellulose, and 5% to 25% wicking agent.
Add the povidone granulating solution to the dry powder blend.
Dry the wet granulation.
Mill the dried granulation.
Add erosion promoter, additional wicking agent, lubricant, and glidant.
Compress the resulting material into a tablet or tablet layer.

A process that omits wet granulation, uses a different binder, or adds the excipients in a materially different sequence would present a stronger non-infringement position under the literal language of claim 1. The composition claims create a separate risk because they do not necessarily require every manufacturing step.

What does claim 2 add?

Claim 2 specifies:

Microcrystalline cellulose or powdered cellulose as the initial wicking agent.
Pregelatinized starch, starch NF, or rice starch at 2 to 15 parts as the erosion promoter.
Sodium starch glycolate, croscarmellose sodium, or crospovidone at 1 to 10 parts as an alternative erosion promoter.
Magnesium stearate or stearic acid as lubricant.
Colloidal or fumed silicon dioxide as glidant.

Claim 4 is the narrowest practical embodiment of this group. It requires water as the granulating liquid, microcrystalline cellulose as the wicking agent, pregelatinized starch as the erosion promoter, and magnesium stearate as lubricant.

What composition is protected by claims 6 through 12?

Claim 6 is the principal composition claim. It requires a shaped and compressed sustained-release therapeutic composition containing:

A pharmaceutical active;
Hydroxyethyl cellulose;
Povidone;
A wicking agent;
An erosion promoter; and
More than 6% but less than approximately 32% total granulating agent and excipients.

Claim 10 narrows the excipient content to more than approximately 6% but less than 15%. Claim 11 applies the same narrower excipient range to the specific formulation in claim 9.

Which active ingredients are covered?

Claim 12 lists:

Codeine;
Codeine phosphate;
Loperamide;
Aspirin;
Naproxen;
Propoxyphene hydrochloride;
Meperidine hydrochloride;
Diphenhydramine;
Pseudoephedrine; and
Pharmaceutically acceptable salts.

The list is closed if interpreted as a Markush limitation. A product containing an active outside the listed group would not fall within claim 12, although it could still implicate claim 6 if the broader claim is otherwise satisfied.

The independent composition claim does not limit the active to acetaminophen. Acetaminophen becomes central in claim 14 and the related bilayer claims.

What formulations are protected by the bilayer claims?

Claims 13 through 18 cover a tablet with:

An immediate-release layer; and
A sustained-release layer containing the claimed matrix system.

The sustained-release layer is prepared by the same general sequence used in claim 1: wet granulation with povidone, drying, milling, addition of erosion promoter and other excipients, and compression with the immediate-release layer.

Claim 14 and acetaminophen

Claim 14 requires a bilayer therapeutic composition with acetaminophen in the sustained-release matrix. It also requires the sustained-release layer to contain:

Hydroxyethyl cellulose;
Povidone;
A wicking agent;
An erosion promoter; and
Less than approximately 32% total granulating agent and excipients.

Claim 16 narrows the excipient content to more than approximately 6% and less than 15%. Claim 17 requires microcrystalline cellulose as wicking agent and pregelatinized starch as erosion promoter.

The language of claim 15 is internally problematic. It states that the immediate-release layer comprises a medicament "which is the same as the medicament in the immediate release layer." Read literally, the limitation is circular and appears to contain a drafting error. It may have intended to require the same medicament in the immediate-release and sustained-release layers. Any enforcement analysis would require prosecution-history review and claim construction.

What does claim 18 add?

Claim 18 provides the most concrete formulation profile:

Part	Ingredient	Range
Part I	Hydroxyethyl cellulose	5 to 25 parts
Part I	Microcrystalline cellulose	5 to 25 parts
Part II	Povidone	5 to 25 parts
Part II	Alcohol or alcohol-water mixture	Quantity sufficient
Part III	Pregelatinized starch	2 to 15 parts
Part III	Microcrystalline cellulose	5 to 45 parts
Part III	Magnesium stearate	0 to 10 parts
Part III	Colloidal silicon dioxide	0 to 5 parts

Claim 18 is narrower than claim 14 because it fixes the wicking agent, erosion promoter, lubricant, and glidant to specific materials and sets explicit ranges.

How strong was the patent estate?

The patent was technically focused but commercially meaningful during its term. Its strongest protection was the combination of:

High active loading;
Hydroxyethyl cellulose;
Povidone wet granulation;
Microcrystalline cellulose;
Pregelatinized starch;
Low total excipient content; and
A bilayer immediate-release/sustained-release architecture.

The estate appears narrower than a broad formulation platform patent because it depends on specific excipient identities, concentration ranges, and processing steps. Design-around opportunities would have included:

Using hydroxypropyl methylcellulose, ethylcellulose, or another release-control polymer instead of hydroxyethyl cellulose;
Replacing povidone with another binder;
Using direct compression rather than wet granulation;
Omitting the bilayer format;
Changing the excipient sequence;
Moving outside the claimed active or excipient ranges; or
Using a different erosion-promoter system.

The composition claims created greater risk than the process claims for a finished-product competitor. A manufacturer could avoid a process claim yet still produce a composition having the claimed ingredient combination and concentration range.

When did Patent 5,004,613 lose exclusivity?

The patent issued on April 2, 1991. Because it predates the Uruguay Round Agreements Act transition rules, its ordinary term was 17 years from issuance under the pre-1995 patent-term regime.[2] The resulting expiration date was April 2, 2008.

Event	Date
Patent issued	April 2, 1991
Ordinary statutory term	17 years from issuance
Expiration	April 2, 2008
Current enforceability	Expired
Current generic-blocking effect	None

Patent-term extension under 35 U.S.C. § 156 applies only in specified regulatory circumstances and would have required a qualifying approved product and an issued extension certificate.[3] No extension is reflected in the claim set provided, and the patent’s term has long ended in any event.

What is the Orange Book status of Patent 5,004,613?

Patent 5,004,613 should not be treated as a current Orange Book barrier. The Orange Book lists patents submitted by an NDA holder for an approved drug product, including relevant drug-substance, drug-product, and method-of-use patents. A patent’s existence does not by itself establish Orange Book listing.[4]

The patent claims formulation processes and dosage-form compositions rather than a current, enforceable exclusivity right. Any historical Orange Book listing would have ceased to create a present patent-exclusivity obstacle after the patent expired. FDA regulatory exclusivity, if separately granted for a particular product, would be distinct from this patent and would not revive the patent’s expired rights.

Are there Paragraph IV challenges to Patent 5,004,613?

A current Paragraph IV challenge to this patent would have no commercial purpose because the patent expired in 2008. Paragraph IV certifications address patents listed for an approved drug in the Orange Book. An ANDA applicant may certify that a listed patent is invalid, unenforceable, or will not be infringed, but an expired patent cannot delay approval as a current patent obstacle.[5]

Historical ANDA disputes may have involved related acetaminophen or sustained-release products, but the supplied record does not establish a particular Paragraph IV notice, ANDA number, settlement, or federal court docket attributable to Patent 5,004,613. The patent’s present risk assessment is unchanged: no current Paragraph IV-related launch block remains.

What patent litigation affects this patent?

The patent cannot support a new infringement action for post-expiration conduct. Under 35 U.S.C. § 286, infringement claims are subject to a six-year damages limitation, and expired patent rights cannot be used to enjoin ongoing commercial activity after expiration.[6]

Potentially relevant historical disputes would have involved:

Whether a sustained-release acetaminophen product contained hydroxyethyl cellulose;
Whether a competitor’s formulation fell within the 6% to 32% excipient limitation;
Whether a bilayer tablet used the claimed immediate-release and sustained-release arrangement;
Whether the accused process performed wet granulation, drying, milling, and final blending in the claimed sequence; and
Whether prosecution-history amendments narrowed the meaning of "wicking agent," "erosion promoter," or "sustained release."

No current litigation exposure can arise solely from practicing the expired claims.

Does the patent create biosimilar risk?

No. Patent 5,004,613 concerns small-molecule pharmaceutical tablets, not a biologic or biosimilar reference product. The Biologics Price Competition and Innovation Act pathway does not apply.[7]

The relevant competitive pathways were historically:

ANDA approval for a therapeutically equivalent generic;
505(b)(2) approval for a modified formulation or dosage form; and
NDA approval for a new branded sustained-release product.

The patent did not create biologic manufacturing or biosimilar barriers.

What manufacturing and intellectual-property barriers remain?

No patent barrier from Patent 5,004,613 remains. Practical barriers may still include:

Developing a reproducible wet-granulation process;
Controlling tablet hardness and dissolution;
Maintaining immediate-release and sustained-release layer integrity;
Demonstrating bioequivalence;
Controlling high active loading;
Managing alcohol-water granulation parameters;
Establishing scale-up conditions; and
Meeting FDA cGMP and dissolution specifications.

Those are technical, regulatory, and manufacturing issues rather than continuing rights under the expired patent.

Geographic coverage

The patent’s rights were limited to the United States. Foreign counterparts, if any, would have required separate national grants and separate term analysis. Expiration of the U.S. patent does not establish the status of corresponding patents in Europe, Canada, Japan, or other jurisdictions.

How does this patent compare with competing sustained-release estates?

Patent 5,004,613 is narrower than patents claiming a broad class of controlled-release polymers or generic multilayer tablet technology. It is stronger against products that reproduce the specified low-excipient matrix and weaker against products using:

A different hydrophilic polymer;
Osmotic delivery;
Coated multiparticulates;
Ion-exchange resins;
Lipid matrices;
Direct-compression systems; or
A non-bilayer dosage form.

Its commercial relevance was highest where the product needed a high active payload and a controlled-release layer without a large polymer load. Its legal relevance today is historical because the claims expired more than 15 years ago.

Key Takeaways

U.S. Patent 5,004,613 covers sustained-release matrix tablets and immediate-release/sustained-release bilayer tablets.
The core formulation uses hydroxyethyl cellulose, povidone, a wicking agent, and an erosion promoter.
Claims 1, 6, 13, 14, and 18 are the principal independent claim groups.
The claims target high active loading, generally 68% to 94% in the process claims.
Acetaminophen is central to the bilayer composition claims, particularly claim 14.
The patent issued April 2, 1991, and expired April 2, 2008 under the pre-1995 17-year patent term.
It creates no current U.S. generic-launch, Paragraph IV, Orange Book, licensing, or infringement barrier.
The patent does not involve biologics or biosimilar risk.
Historical importance lies in the formulation architecture, not in any surviving exclusivity.

FAQs About U.S. Patent 5,004,613

What drug product was associated with U.S. Patent 5,004,613?

The claim set is directed to sustained-release pharmaceutical tablets, including acetaminophen bilayer tablets and products containing codeine, loperamide, aspirin, naproxen, propoxyphene, meperidine, diphenhydramine, and pseudoephedrine.

Can a company use the claimed hydroxyethyl cellulose formulation today?

Yes, in the United States, the patent expired on April 2, 2008. Separate patents, regulatory exclusivities, trademarks, or foreign rights would require independent review.

Is claim 18 broader than claim 14?

No. Claim 18 is narrower because it specifies microcrystalline cellulose, pregelatinized starch, magnesium stearate, colloidal silicon dioxide, and defined ingredient ranges.

Could a direct-compression tablet infringe claim 1?

A direct-compression product would have a strong argument against literal infringement of claim 1 because that claim requires wet granulation, drying, milling, and subsequent blending. The expired composition claims would still have been relevant during the patent term.

Does expiration eliminate FDA bioequivalence requirements?

No. Patent expiration removes the patent obstacle but does not eliminate FDA requirements for ANDA approval, including pharmaceutical equivalence, bioequivalence, manufacturing controls, and product quality requirements.

References

United States Patent No. 5,004,613, claims 1-20 (issued Apr. 2, 1991).
35 U.S.C. § 154(a)(2) (pre-Uruguay Round patent-term rules for qualifying patents).
35 U.S.C. § 156 (patent-term extension for regulatory review).
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations (Orange Book).
21 U.S.C. § 355(j)(2)(A)(vii), (j)(2)(A)(vii)(IV) (ANDA patent certifications).
35 U.S.C. § 286 (limitation on damages for patent infringement).
Public Law 111-148, § 7002, 124 Stat. 119, 804-821 (2010) (Biologics Price Competition and Innovation Act).

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2001288	⤷ Start Trial
Australia	611704	⤷ Start Trial
Canada	1315202	⤷ Start Trial
Germany	3880762	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 5,004,613

Summary for Patent: 5,004,613