United States Drug Patent 4,820,522: Claim Scope, Expiration, FDA Status, and Acetaminophen Patent Landscape

U.S. Patent No. 4,820,522 covers sustained-release acetaminophen tablets, including monolithic tablets and immediate-release/sustained-release bilayer tablets. Its central technical concept is a high-acetaminophen matrix containing hydroxyethyl cellulose and povidone, produced by wet granulation and finished with erosion-promoting, wicking, lubricating, and glidant excipients.

The patent issued on April 11, 1989. Because it was issued from a pre-June 8, 1995 application regime, its ordinary patent term was 17 years from issuance under 35 U.S.C. § 154(c)(1). On that basis, the patent expired on April 11, 2006, absent an unusual terminal-disclaimer or court-order issue. The claims therefore do not presently create an enforceable U.S. patent barrier to generic acetaminophen extended-release products.[1]

What does U.S. Patent 4,820,522 protect?

The patent protects three related subject-matter groups:

Manufacturing processes for sustained-release acetaminophen tablets.
Sustained-release acetaminophen compositions containing hydroxyethyl cellulose and povidone.
Bilayer tablets combining an immediate-release acetaminophen layer with a sustained-release acetaminophen layer.

The patent is formulation- and process-specific. It does not broadly cover all extended-release acetaminophen products.

Patent identification and legal status

Item	Information
U.S. patent	4,820,522
Issue date	April 11, 1989
Technology	Sustained-release acetaminophen tablets
Dosage forms	Compressed tablets and bilayer tablets
Primary release mechanism	Hydrophilic matrix with erosion and wicking components
Key matrix polymer	Hydroxyethyl cellulose
Key granulating binder	Povidone
Active ingredient range	Generally 68% to 94% acetaminophen by weight
Ordinary expiration	April 11, 2006
Current enforceability	Expired
Paragraph IV relevance today	None for this expired patent
Biosimilar relevance	None; acetaminophen is a small-molecule drug

The patent’s claims should be read as a coordinated formulation platform rather than as protection for acetaminophen itself. Acetaminophen was long known before the patent, and the patent does not claim the active ingredient as a new chemical entity.

How broad are claims 1 through 5 for the manufacturing process?

Claims 1 through 5 cover a wet-granulation process for a sustained-release acetaminophen tablet.

Claim 1: independent process claim

Claim 1 requires all of the following:

Povidone dissolved in water or an alcohol-water mixture.
Povidone at 5% to 25% by weight of the total composition.
Acetaminophen at 68% to 94% by weight.
Hydroxyethyl cellulose at 5% to 25%.
A wicking agent at 5% to 25%.
Wet granulation of the dry powders with the povidone granulating solution.
Drying and milling of the granulation.
Final blending with:
- an erosion promoter at 1% to 15%;
- a wicking agent at 5% to 45%;
- a lubricant at 0% to 10%; and
- a glidant at 0% to 5%.
Compression into a tablet or tablet layer.

The claim is narrow in two ways. First, it requires a particular sequence of manufacturing operations. Second, it requires specified concentration ranges and excipient categories. A product using the same ingredients but manufactured by direct compression, dry granulation, spray drying, or a materially different sequence would not literally satisfy every limitation of claim 1.

The claim does not require a particular dissolution profile, tablet weight, tablet hardness, acetaminophen dose, or release duration. The phrase “characterized by a slow release” supplies a functional result but does not establish a precise dissolution specification in the claim text.

Claim 2: listed excipient classes

Claim 2 narrows claim 1 by defining the excipient options:

Microcrystalline cellulose or powdered cellulose as the initial wicking agent.
Pregelatinized starch, starch NF, rice starch, sodium starch glycolate, croscarmellose sodium, or crospovidone as the erosion promoter.
Magnesium stearate or stearic acid as the lubricant.
Colloidal silicon dioxide or fumed silicon dioxide as the glidant.

This claim is more commercially relevant than claim 1 because it maps more closely to conventional pharmaceutical excipient systems.

Claims 3 through 5: preferred formulation and 325 mg tablet

Claim 3 limits the process to:

water as the solvent;
microcrystalline cellulose as the wicking agent;
pregelatinized starch as the erosion promoter; and
magnesium stearate as the lubricant.

Claim 4 specifies the formulation:

Ingredient	Amount
Acetaminophen	325.0 parts
Hydroxyethyl cellulose	10.7 parts
Povidone	10.7 parts
Pregelatinized starch	5.0 parts
Microcrystalline cellulose	15.0 parts
Magnesium stearate	5.0 parts
Water	Quantity sufficient

Claim 5 clarifies that the amounts may represent milligrams per tablet. The preferred formulation therefore describes a 325 mg acetaminophen tablet with approximately 46.4 mg of listed dry excipients, before accounting for water removed during drying.

What do claims 6 and 9 protect for the sustained-release composition?

Claims 6 and 9 are composition claims rather than manufacturing claims.

Claim 6: hydrophilic sustained-release matrix

Claim 6 requires:

a shaped and compressed therapeutic composition;
acetaminophen;
a granulating agent and excipients combined into a matrix;
hydroxyethyl cellulose;
povidone; and
total granulating agent and excipients below approximately 35% of the composition weight.

The claim uses a functional limitation: the excipients must be present in an amount effective to bind acetaminophen in a sustained-release solid matrix.

This claim is potentially broader than claim 1 because it does not expressly require the complete wet-granulation sequence. It also does not require the named erosion promoter, lubricant, or glidant categories found in the process claims.

Claim 9: narrower excipient loading

Claim 9 limits claim 6 by requiring that the total granulating agent and excipients be:

greater than approximately 6%; and
less than 15% of the total composition weight.

Claim 9 is commercially significant because it focuses on a relatively low-excipient, high-drug-load matrix. It may have been intended to distinguish a sustained-release matrix from conventional formulations with substantially higher polymer or excipient content.

The terms “about,” “effective,” and “slow release” expand interpretive flexibility but can also create litigation issues. The claim does not provide a numerical dissolution endpoint, release-rate range, or test method. Any infringement analysis would require the specification, prosecution history, and potentially expert testimony concerning how a skilled person would understand those terms in 1989.

What do claims 7 and 8 protect as product-by-process claims?

Claim 7 covers a sustained-release acetaminophen tablet made by:

wet granulating acetaminophen with hydroxyethyl cellulose and microcrystalline cellulose;
using povidone in water or an alcohol-water mixture as the granulating agent;
drying and milling the granulation;
blending it with pregelatinized starch, microcrystalline cellulose, magnesium stearate, and colloidal silicon dioxide; and
compressing the mixture into a tablet.

The specified ranges are:

Component	Range, parts by weight
Acetaminophen	68% to 94% of composition
Hydroxyethyl cellulose	5 to 25
Microcrystalline cellulose in Part I	5 to 25
Povidone	5 to 25
Pregelatinized starch	2 to 15
Microcrystalline cellulose in Part III	5 to 45
Magnesium stearate	0 to 10
Colloidal silicon dioxide	0 to 5

Claim 8 permits the parts-by-weight values to represent milligrams per tablet or proportional fractions.

The legal significance of claim 7 is that it is directed to a tablet “made by” a specified process. Under longstanding U.S. patent law, product-by-process language generally limits the claim for infringement purposes when the accused product is made by a different process, although the resulting product must still satisfy the claimed product characteristics. The exact treatment depends on claim construction and controlling precedent.[2]

For a generic applicant, claim 7 creates a design-around path if the commercial tablet uses a different manufacturing route or a different excipient system. Because the patent is expired, that path now has commercial rather than litigation significance.

What do claims 10 through 17 protect for bilayer tablets?

Claims 10 through 17 extend the invention to a two-layer dosage form.

Bilayer architecture

The claimed tablet has:

a first immediate-release acetaminophen layer; and
a second sustained-release acetaminophen layer.

The sustained-release layer uses the same central platform:

acetaminophen at 68% to 94% of the sustained-release layer;
hydroxyethyl cellulose;
microcrystalline cellulose or another wicking agent;
povidone dissolved in alcohol or an alcohol-water mixture;
an erosion promoter;
a lubricant; and
a glidant.

Claim 10 requires the process of preparing the two layers and compressing them together. Claims 14 and 16 cover the bilayer composition based on the sustained-release layer’s excipient loading.

Immediate-release layer

Claims 13 and 15 define the immediate-release layer using:

acetaminophen;
powdered cellulose;
starch;
pregelatinized starch;
sodium lauryl sulfate; and
a granulating agent.

The patent therefore claims release sequencing through tablet architecture rather than solely through polymer concentration. The immediate-release layer is intended to provide an initial acetaminophen dose, while the hydrophilic matrix layer provides delayed or prolonged release.

Claim 17: bilayer product-by-process

Claim 17 recites a bilayer tablet made by combining an immediate-release layer with a sustained-release layer having the Part I, Part II, and Part III excipient system.

The claim is narrower than a generic bilayer claim because it requires the specified sustained-release formulation and manufacturing sequence. A competitor using a multilayer tablet with a different matrix polymer, different binder, or different granulation method would have strong noninfringement positions against the literal claim language.

Which technical features form the core patent scope?

The patent’s strongest technical limitations are the combination of:

high acetaminophen loading;
hydroxyethyl cellulose as a matrix-forming or release-controlling excipient;
povidone as a wet-granulation binder;
a defined wet-granulation, drying, milling, and final-blending sequence;
post-granulation incorporation of erosion-promoting starch or superdisintegrant;
microcrystalline cellulose as a wicking agent; and
compression into a monolithic or bilayer tablet.

The claims do not broadly cover every hydrophilic matrix. They identify a specific interaction between a cellulose-based matrix, a povidone binder, and excipients that promote liquid penetration and matrix erosion.

Claim dependency and drafting issues

The claim set contains several drafting characteristics relevant to scope analysis:

Claims 1 and 10 use broad process language but impose multiple quantitative ranges.
Claim 4 identifies a preferred 325 mg-type formulation.
Claim 6 uses functional language instead of a detailed dissolution specification.
Claim 7 uses product-by-process language.
Claims 10 through 17 repeat much of the monolithic tablet platform for a bilayer form.
Claim 10 requires alcohol or an alcohol-water mixture, while claim 1 permits water alone.
Claim 12 narrows the bilayer process to high-shear granulation and specific excipients.

These distinctions matter because an accused formulation may fall outside one claim while still implicating another. For example, a tablet may avoid claim 1 by using direct compression but still require analysis under claim 6 if it contains the claimed matrix composition.

When does U.S. Patent 4,820,522 lose exclusivity?

The patent’s ordinary term ended in 2006.

Event	Date
Patent issued	April 11, 1989
Ordinary 17-year term begins for pre-1995 patent	April 11, 1989
Ordinary expiration	April 11, 2006
Current status	Expired by term

Patent term adjustment and patent term extension regimes associated with later-issued patents do not ordinarily convert a 1989 patent into a currently enforceable right. Patent term extension under 35 U.S.C. § 156 is generally associated with regulatory review of qualifying products, but it cannot be presumed from the patent claims alone and would require a recorded extension.[3]

What is the Orange Book status of this patent?

U.S. Patent 4,820,522 does not create a current Orange Book barrier because it expired in 2006.

Orange Book-listed patents are tied to approved drug products and their associated patent certifications. For a currently marketed acetaminophen extended-release product, the relevant questions are:

whether the product is listed under an approved NDA;
whether any formulation, method-of-use, or drug-delivery patents are listed;
whether those patents remain unexpired; and
whether an ANDA applicant must certify under section 505(j)(2)(A)(vii) of the Federal Food, Drug, and Cosmetic Act.[4]

An expired patent may remain historically relevant to product development but does not support a present Paragraph IV challenge. Paragraph IV certification is directed to a listed patent that the applicant asserts is invalid, unenforceable, or not infringed. Once the patent has expired, the practical certification issue is generally no longer a launch blocker.

Are there Paragraph IV challenges or generic entry risks?

There is no current Paragraph IV risk associated with U.S. Patent 4,820,522 itself because its term expired in 2006.

The relevant present-day risks for an acetaminophen extended-release generic would instead arise from:

later formulation patents;
patents covering a specific dissolution profile;
bilayer or multilayer tablet architecture;
abuse-deterrent or modified-release delivery systems;
manufacturing patents;
method-of-use patents;
product-specific Orange Book listings; and
regulatory exclusivity unrelated to this patent.

Acetaminophen is a small molecule. Biosimilar pathways under the Public Health Service Act are not relevant. An extended-release acetaminophen product would ordinarily proceed through an ANDA only if it can demonstrate the required pharmaceutical equivalence, bioequivalence, labeling conformity, and quality attributes. A formulation that differs materially from the reference product may require a different regulatory pathway or additional clinical and pharmacokinetic support.[5]

What manufacturing and intellectual-property barriers remain?

The expired patent leaves the formulation concept open to practice, but commercial development still faces technical barriers:

Dissolution control

Extended-release acetaminophen products must achieve reproducible release across multiple dissolution media and manufacturing lots. Small changes in hydroxyethyl cellulose viscosity, granulation endpoint, particle-size distribution, moisture content, compression force, and tablet porosity can alter release performance.

High drug loading

The claimed 68% to 94% acetaminophen range leaves limited room for excipients. That creates manufacturing pressure around flow, compactability, capping, friability, and dose uniformity.

Bilayer compression

Bilayer products require control of:

layer weight;
interfacial bonding;
cross-contamination between layers;
compression force;
layer separation; and
immediate-release versus sustained-release dissolution performance.

Regulatory equivalence

A generic applicant must match the reference product’s dosage form and release characteristics, not merely reproduce the expired patent’s ingredients. The FDA may evaluate pharmacokinetic exposure, partial AUC, food effects, dose dumping, and dissolution profile similarity depending on the product and approved product-specific guidance.

Are there licensing deals associated with this patent?

The patent claims do not establish a licensing arrangement. A patent document identifies inventorship and ownership information at the relevant record date, but it does not prove the existence, duration, economics, or continuing effect of a commercial license.

Because the patent expired in 2006, any historical license would now have limited relevance to freedom to operate unless it included surviving contractual obligations, know-how rights, confidentiality provisions, or technology-transfer restrictions. Patent exhaustion and expiration generally prevent the expired patent from supporting continuing patent royalties for ordinary U.S. practice of the claimed invention, but contract rights must be analyzed separately from patent rights.[6]

How strong is the patent estate for acetaminophen extended release?

The estate represented by U.S. Patent 4,820,522 is historically important but commercially weak today because the patent is expired.

Dimension	Assessment
Chemical composition protection	Weak; acetaminophen itself is not claimed as a new molecule
Formulation protection	Moderate while live; focused on polymer and excipient combinations
Process protection	Moderate while live; requires wet granulation and defined processing steps
Bilayer protection	Moderate while live; limited by specific layer and excipient requirements
Breadth	Narrow to moderate
Design-around potential	Material
Current enforceability	None after expiration
Biosimilar exposure	Not applicable
Current generic barrier	None from this patent

The main commercial value was the ability to protect a particular high-drug-load matrix formulation and manufacturing process during the patent term. The patent did not create a durable platform monopoly over all sustained-release acetaminophen tablets.

What patent litigation and settlements affect the patent?

No current litigation or settlement can be attributed to an expired patent solely from the claim text. Historical litigation, assignments, terminal disclaimers, licensing agreements, and continuation relationships must be confirmed through the USPTO patent file, court dockets, and assignment records.

A present infringement action based only on U.S. Patent 4,820,522 would face the threshold expiration problem. A settlement involving later patents could still reference the technology, but such an agreement would not revive the expired patent or extend its statutory term.

How does this patent compare with modern extended-release formulation patents?

U.S. Patent 4,820,522 relies on a conventional hydrophilic matrix approach. Modern modified-release patents often claim more targeted variables, such as:

polymer viscosity grades;
coating compositions;
multiparticulates;
osmotic delivery systems;
multilayer geometry;
abuse-deterrent matrices;
dissolution specifications;
food-effect control;
dose-dumping resistance; and
manufacturing process parameters tied to scale-up.

The 1989 patent’s claim language is relatively ingredient- and process-centered. Later patents are more likely to combine formulation composition with measured release performance and product-specific pharmacokinetic characteristics.

Key Takeaways

U.S. Patent 4,820,522 covers sustained-release acetaminophen tablets and bilayer tablets.
Its central platform combines high acetaminophen loading with hydroxyethyl cellulose, povidone, microcrystalline cellulose, starch-based erosion promoters, and wet granulation.
Claims 1 through 5 focus on monolithic-tablet manufacturing.
Claims 6 and 9 focus on sustained-release matrix compositions.
Claims 7 and 8 cover a specified tablet made by a defined process.
Claims 10 through 17 cover immediate-release/sustained-release bilayer tablets.
The patent issued April 11, 1989, and its ordinary term expired April 11, 2006.
The patent has no current Paragraph IV or Orange Book blocking effect.
Biosimilar risk is irrelevant because acetaminophen is a small molecule.
Current market risk would arise from later patents, product-specific FDA requirements, manufacturing reproducibility, and bioequivalence requirements.
The patent’s historical scope was meaningful but its present patent-enforcement value is zero after expiration.

FAQs

Can a company manufacture a sustained-release acetaminophen tablet using the exact formulation in Patent 4,820,522?

Yes, the expired patent no longer prevents practice of its claimed U.S. formulation or process, subject to any separate, unexpired patent rights and applicable FDA requirements.

Does the patent cover Tylenol 8 HR or every 650 mg extended-release acetaminophen product?

No. The patent does not automatically cover a branded product or every extended-release acetaminophen tablet. Coverage depends on the product’s ingredients, ranges, manufacturing process, dosage form, and any later patents.

Can a generic applicant rely on the expired patent to establish FDA approval?

No. The patent may provide technical disclosure, but FDA approval requires compliance with the applicable ANDA or NDA pathway, including pharmaceutical equivalence, bioequivalence, quality, labeling, and manufacturing requirements.

Does using hydroxyethyl cellulose alone infringe the patent?

Not necessarily. Several claims also require povidone, acetaminophen concentration ranges, specific excipients, processing steps, or a bilayer structure. Hydroxyethyl cellulose alone is insufficient to establish infringement.

Does expiration eliminate all commercial value associated with the patented technology?

It eliminates the patent’s exclusionary value, but the formulation and manufacturing disclosure may still have technical value. Know-how, trade secrets, regulatory data, trademarks, and separate later patents are not automatically extinguished by expiration of this patent.

References

United States Patent and Trademark Office. (1989). U.S. Patent No. 4,820,522: Sustained release acetaminophen compositions.
U.S. Supreme Court. (2009). Bilski v. Kappos, 561 U.S. 593.
35 U.S.C. §§ 154, 156.
Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 355(j).
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations.
U.S. Supreme Court. (2008). Quanta Computer, Inc. v. LG Electronics, Inc., 553 U.S. 617.

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
European Patent Office	0305051	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Summary for Patent: 4,820,522