United States Patent 4,389,393: Scope, Claims, Expiration, and Sustained-Release HPMC Patent Landscape

U.S. Patent No. 4,389,393 covers compressed solid dosage forms that use hydroxypropylmethylcellulose, or HPMC, as a low-level matrix-forming carrier to provide regular, prolonged drug release. The claims reach formulations containing less than approximately one-third HPMC-based carrier by weight, provided that at least one HPMC has specified methoxy, hydroxypropoxy, and molecular-weight characteristics.

The patent issued on June 21, 1983, and, as a pre-Uruguay Round patent, its original 17-year term from issuance would have ended on June 21, 2000, absent an unusual term adjustment or later extension. It is therefore not an enforceable barrier to current generic or branded products.

What does U.S. Patent 4,389,393 cover?

The patent covers a compressed pharmaceutical matrix in which HPMC controls the release of an active medicament. The principal technical concept is the use of a relatively small quantity of a high-molecular-weight cellulose ether to produce sustained release.

The core formulation must contain:

Claim limitation	Requirement
Dosage form	Solid unit dosage form
Manufacturing form	Mixture is shaped and compressed
Release profile	Regular and prolonged release upon administration
Primary carrier	One or more HPMCs
Optional carrier components	Up to 30% of the carrier mixture may be methylcellulose, sodium carboxymethylcellulose, or another cellulose ether
Required HPMC chemistry	Methoxy content of 16-24 wt.%
Required HPMC chemistry	Hydroxypropoxy content of 4-32 wt.%
Required polymer size	Number-average molecular weight of at least 50,000
Carrier loading	Less than approximately one-third of the total dosage-form weight

The patent is directed to matrix tablets rather than coated reservoir systems, osmotic systems, multiparticulate capsules, transdermal systems, or injectable dosage forms.

What is the inventive concept?

The claims combine four elements:

A compressed tablet or comparable solid unit dosage form.
An HPMC matrix capable of controlling drug diffusion and matrix erosion.
A specific range of HPMC substitution levels and molecular weight.
A carrier concentration below approximately 33.3% of the final dosage-form weight.

The low carrier loading is significant. Many sustained-release matrix claims rely on a relatively high polymer concentration. This patent instead claims prolonged release while limiting the HPMC-based carrier to less than one-third of the dosage form.

How should independent claim 1 be construed?

Claim 1 is the principal composition claim. It requires both structural and functional limitations.

“Carrier base material”

The carrier base material must be:

One or more HPMCs; or
HPMC combined with up to 30% of the carrier mixture consisting of methylcellulose, sodium carboxymethylcellulose, and/or another cellulose ether.

The 30% limitation applies to the carrier mixture, not necessarily to the complete tablet. For example, a carrier mixture could contain 70% HPMC and 30% sodium carboxymethylcellulose. The total carrier mixture must still account for less than approximately one-third of the dosage form.

HPMC substitution ranges

At least one HPMC must have:

Methoxy content of 16-24 wt.%; and
Hydroxypropoxy content of 4-32 wt.%.

These parameters identify substituted cellulose ethers with both methoxyl and hydroxypropoxyl groups. The claim does not require every HPMC in a multi-HPMC formulation to fall within the stated ranges. It requires that at least one HPMC satisfy them.

The ranges are broad enough to encompass multiple commercial HPMC grades, subject to the molecular-weight and release-performance limitations.

Molecular-weight limitation

The qualifying HPMC must have a number-average molecular weight of at least 50,000. This excludes lower-molecular-weight cellulose ethers that may function primarily as binders, viscosity modifiers, or disintegrant-support materials.

The claim refers to number-average molecular weight, not viscosity grade. A product label identifying only a compendial viscosity grade may not, by itself, establish whether the molecular-weight limitation is met. Analytical characterization or manufacturer specifications would ordinarily be relevant.

“Less than about one third”

This is a quantitative limitation with some drafting flexibility. “Less than one third” is relatively definite. The word “about” introduces tolerance around the one-third threshold, but it does not eliminate the requirement that the carrier be materially below or near 33.3% of the dosage form.

A formulation containing 40% HPMC-based carrier would present a substantial noninfringement argument under the literal claim language. A formulation near 33% would require closer analysis of measurement methods, batch variability, and the meaning of “about.”

“Regular and prolonged release pattern”

This is a functional limitation. The claim does not specify a universal dissolution window, release percentage, or testing protocol in the text supplied. As a result, infringement analysis would depend on:

The active ingredient;
Dose and solubility;
Tablet dimensions and hardness;
Polymer grade;
Dissolution medium;
Agitation rate;
Sampling intervals; and
The patent specification and prosecution history.

A tablet does not fall within the claim merely because it contains HPMC. It must also produce the claimed regular and prolonged release pattern.

What do dependent claims 2 through 9 add?

Claim	Added limitation	Commercial significance
2	HPMC plus 0-30% sodium carboxymethylcellulose	Covers mixed HPMC/NaCMC carrier systems
3	HPMC plus 0-30% methylcellulose or another cellulose ether	Broadens the secondary cellulose-ether combination
4	Active medicament is moisture sensitive	Targets drugs susceptible to degradation or instability from moisture
5	Enumerated moisture-sensitive drugs and drug classes	Provides a long species list but remains dependent on claim 4
6	Active is lithium carbonate	Relevant to sustained-release lithium products
7	Active is phenylpropanolamine	Relevant to extended-release sympathomimetic products
8	Active is potassium chloride	Relevant to controlled-release electrolyte tablets
9	Active is an anti-inflammatory drug	Includes ibuprofen, flurbiprofen, diclofenac, indomethacin, and naproxen

Claim 5: moisture-sensitive drugs

Claim 5 identifies a broad list of drug substances, including aspirin, theophylline, nitroglycerin, isosorbide dinitrate, lithium-related compounds, analgesics, antihistamines, steroids, antibiotics, and other pharmaceutical classes.

The phrase “selected from but not limited to” attempts to preserve scope beyond the listed compounds. Its effectiveness depends on the surrounding claim language and applicable claim-construction principles. The claim still requires the active medicament to be moisture sensitive and the formulation to satisfy all limitations inherited from claim 4 and claim 1.

Claims 6 through 9: species claims

These claims narrow the invention to particular active ingredients or drug classes. They may have been useful during prosecution or enforcement because they identify commercial product categories with established sustained-release demand.

A species claim is not infringed merely because a product contains the specified active ingredient. The product must also contain the claimed HPMC carrier, satisfy the substitution and molecular-weight parameters, remain below the carrier-loading threshold, and exhibit the required release pattern.

What does claim 10 cover?

Claim 10 is the independent method claim. It covers preparing the dosage form by compressing and shaping a mixture of:

A therapeutically active medicament; and
The specified HPMC-based carrier system.

The method repeats the principal limitations of claim 1, including:

HPMC as the primary carrier;
Optional cellulose ethers at up to 30% of the carrier mixture;
Methoxy content of 16-24 wt.%;
Hydroxypropoxy content of 4-32 wt.%;
Number-average molecular weight of at least 50,000;
Carrier content below approximately one-third of the solid dosage form.

Does claim 10 cover direct compression only?

The supplied language requires compressing and shaping the mixture, but it does not expressly require that the process be direct compression. A process using granulation, blending, drying, and final compression could potentially fall within the claim if the claimed mixture and final composition are present and the process satisfies the claim language.

The claim does not expressly require:

A particular compression force;
A specified tablet hardness;
Wet granulation;
Dry granulation;
A coating;
A specific dissolution apparatus; or
A particular active-drug loading.

How strong is the patent estate for U.S. Patent 4,389,393?

The patent was technically important as a foundational HPMC sustained-release matrix patent, but its current legal strength is zero because the patent term expired decades ago.

Historical strengths

The patent had several potentially valuable features during its term:

It claimed a broad class of HPMC matrix tablets.
It covered low polymer loading.
It included both composition and manufacturing claims.
It covered multiple drug classes and specific active ingredients.
It defined HPMC through chemical substitution and molecular-weight parameters rather than by trade name alone.
It addressed moisture-sensitive drugs, a commercially important formulation problem.

Historical weaknesses

The claims also had vulnerabilities:

“Regular and prolonged release pattern” is functional and potentially fact intensive.
The term “about” creates flexibility but can introduce boundary disputes.
The claim depends on molecular-weight characterization that may vary by analytical method.
HPMC was a known pharmaceutical excipient, creating potential obviousness and anticipation issues depending on the prior art.
The claims require a particular combination of polymer chemistry, loading, and release behavior rather than merely the presence of HPMC.

When did U.S. Patent 4,389,393 lose exclusivity?

The patent’s ordinary term ended on June 21, 2000, based on its June 21, 1983 issue date and the 17-year term applicable to many pre-June 8, 1995 U.S. patents. The patent is now expired and cannot block manufacture, sale, or approval of an otherwise lawful product.

Event	Date
Patent issued	June 21, 1983
Ordinary 17-year expiration	June 21, 2000
Current status	Expired
Current enforceability	None

A patent expiration date is distinct from FDA regulatory exclusivity. Expiration of this patent does not establish approval status for any drug product, and FDA approval does not revive an expired formulation patent.

What is the Orange Book status of U.S. Patent 4,389,393?

U.S. Patent 4,389,393 is not itself an Orange Book drug listing. The FDA Orange Book lists patents submitted by sponsors for approved drug products, not every pharmaceutical technology patent issued by the USPTO.

The patent could historically have been relevant to an approved extended-release product if a sponsor submitted it as a formulation or drug-product patent. The patent number, however, cannot be treated as an Orange Book-listed patent without a product-specific Orange Book record.

The patent’s expiration also means that it presents no current Paragraph IV barrier.

Are there Paragraph IV challenges or generic litigation risks?

No current Paragraph IV challenge is necessary to defeat this patent because it has expired. A Paragraph IV certification is directed to a patent listed for an approved reference product. The legal risk from an expired patent is materially different from the risk created by an unexpired Orange Book-listed patent.

For current generic products, the principal risks would instead arise from:

Later HPMC formulation patents;
Drug-specific extended-release patents;
Dissolution-profile patents;
Coating or multiparticulate patents;
Manufacturing-process patents;
Dosage-regimen patents;
Pediatric or abuse-deterrent formulations; and
Patent rights covering a specific commercial product.

Does the patent create biosimilar risk?

No. Biosimilar regulation concerns biological products. U.S. Patent 4,389,393 covers compressed solid dosage forms and small-molecule pharmaceutical compositions. It has no direct relevance to biosimilar approval under the Biologics Price Competition and Innovation Act.

What formulations are protected by the patent?

The patent can cover a conventional HPMC matrix tablet if all claimed elements are present. Representative formulation categories include:

Lithium carbonate sustained-release tablets;
Potassium chloride extended-release tablets;
Phenylpropanolamine sustained-release tablets;
Nonsteroidal anti-inflammatory drug matrix tablets;
Moisture-sensitive active ingredients formulated with HPMC;
HPMC/NaCMC matrices;
HPMC/methylcellulose matrices; and
HPMC matrices containing other cellulose ethers within the specified proportion.

The claims do not expressly require an external film coat. A coated tablet could still fall within the claims if the underlying solid unit dosage form satisfies the limitations.

What formulations fall outside the literal claim scope?

Potential noninfringing designs include formulations that:

Use no HPMC;
Use HPMC that does not meet the claimed substitution ranges;
Use only HPMC with a number-average molecular weight below 50,000;
Contain a carrier amount materially above the one-third limitation;
Use a noncompressed dosage form;
Use a liquid, capsule, implant, patch, or injectable system;
Do not provide a regular and prolonged release pattern; or
Use a different release-control mechanism, such as an osmotic pump or reservoir membrane.

A formulation can avoid literal infringement while still requiring analysis under the doctrine of equivalents. Because the patent expired in 2000, that analysis has no present enforcement consequence.

How does this patent compare with later HPMC patent strategies?

Patent strategy	Typical claim focus	Relationship to U.S. 4,389,393
Foundational HPMC matrix	HPMC chemistry, molecular weight, low carrier loading, prolonged release	Directly represented by U.S. 4,389,393
Drug-specific matrix	One active ingredient and defined dissolution profile	Narrower and often commercially targeted
Polymer-blend formulation	HPMC combined with carbomer, alginate, or other polymers	Potentially distinct from the claimed cellulose-ether combinations
Coated matrix tablet	HPMC core plus film coating	Adds coating limitations not required by this patent
Multiparticulate system	Pellets, beads, granules, or coated particles	Generally outside the compressed-unit focus
Osmotic dosage form	Semipermeable membrane and osmotic engine	Mechanistically distinct
Manufacturing process	Granulation, drying, compression, or coating parameters	May create later process-specific barriers
Dissolution method	Defined in vitro release profile	Can provide a separate product-specific claim strategy

The patent’s main legacy is its broad matrix-platform approach. Later patent portfolios generally narrowed the technology to a particular active ingredient, formulation architecture, release curve, or manufacturing process.

What manufacturing and intellectual-property barriers remain?

Although U.S. 4,389,393 is expired, a current manufacturer must still assess:

HPMC supplier specifications;
Polymer substitution and viscosity grades;
Molecular-weight characterization;
Tablet compression behavior;
Drug-polymer compatibility;
Moisture control;
Dissolution reproducibility;
Scale-up effects;
Process validation;
Drug-specific patents;
Orange Book-listed patents for the reference product;
Foreign patent rights; and
Regulatory requirements for extended-release products.

The expired patent does not eliminate technical barriers. HPMC matrix products can show sensitivity to particle size, tablet hardness, polymer hydration, agitation conditions, and active-ingredient solubility.

What is the geographic coverage?

U.S. Patent 4,389,393 provides rights only in the United States. Related patent applications may have existed in other jurisdictions, but foreign rights must be assessed independently by country.

A U.S. expiration does not establish that corresponding European, Canadian, Japanese, or other national rights expired on the same date. For a current launch, the relevant analysis should distinguish:

U.S. patent status;
European national validations;
Patent Cooperation Treaty applications;
Continuations and divisionals;
Foreign formulation patents; and
Country-specific supplementary protection or term-extension mechanisms.

What licensing deals are associated with the patent?

The technology was associated with commercial HPMC sustained-release formulation technology and cellulose-ether products, but the claim set alone does not establish a license, assignment, or royalty arrangement for any commercial drug.

A patent assignment is distinct from a technology license. The patent’s commercial relevance may have reflected access to HPMC excipients, formulation know-how, or commercial development agreements rather than a license limited to the patent claims.

Key Takeaways

U.S. Patent 4,389,393 covers compressed sustained-release dosage forms using HPMC-based matrices.
The qualifying HPMC must have 16-24% methoxy, 4-32% hydroxypropoxy, and a number-average molecular weight of at least 50,000.
The carrier must constitute less than approximately one-third of the dosage form.
Claims 2 and 3 cover limited HPMC blends with sodium carboxymethylcellulose, methylcellulose, or other cellulose ethers.
Claims 4 through 9 target moisture-sensitive drugs, lithium carbonate, phenylpropanolamine, potassium chloride, and anti-inflammatory drugs.
Claim 10 covers the compression and shaping method.
The patent’s ordinary term expired on June 21, 2000.
It presents no current U.S. patent-enforcement, Paragraph IV, Orange Book, or biosimilar barrier.
Current commercial risk would come from later drug-specific, formulation, manufacturing, dissolution, or foreign patents.

FAQs About U.S. Patent 4,389,393

Is U.S. Patent 4,389,393 still enforceable?

No. Its ordinary patent term ended on June 21, 2000.

Does every HPMC extended-release tablet infringe this patent?

No. The product must satisfy all relevant limitations, including HPMC chemistry, molecular weight, carrier loading, compression, and prolonged-release behavior.

Does the patent cover HPMC capsules?

The supplied claims focus on a shaped and compressed solid unit dosage form. A conventional liquid-filled or powder-filled capsule would not ordinarily satisfy that limitation without additional facts about the claimed dosage form.

Does the patent cover a tablet containing more than 33% HPMC?

Generally, such a formulation would present a strong argument that it falls outside the express “less than about one third” carrier limitation, although the exact composition calculation and interpretation of “about” would matter.

Is U.S. Patent 4,389,393 relevant to current generic potassium chloride products?

It may be historically relevant to the formulation technology, but it does not block current products because the patent expired. Current risk must be assessed against later patents and any drug-product patents listed for the applicable reference product.

References

United States Patent and Trademark Office. (1983). U.S. Patent No. 4,389,393. Sustained-release pharmaceutical composition. https://patents.google.com/patent/US4389393
United States Code, 35 U.S.C. § 154. Patent term.
United States Code, 21 U.S.C. § 355(j). Abbreviated new drug applications and patent certifications.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations. Orange Book. https://www.fda.gov/drugs/drug-approvals-and-databases/orange-book-data-files
U.S. Food and Drug Administration. (2024). Guidance for industry: Extended release oral dosage forms: Development, evaluation, and application of in vitro/in vivo correlations. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/extended-release-oral-dosage-forms-development-evaluation-and-application-vitroin-vivo-correlations

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	230569	⤷ Start Trial
Australia	5676186	⤷ Start Trial
Australia	583616	⤷ Start Trial
Belgium	896136	⤷ Start Trial
Brazil	8300260	⤷ Start Trial
Canada	1188614	⤷ Start Trial
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Details for Patent: 4,389,393

Summary for Patent: 4,389,393