US Patent 4,892,741: Scope, Claims, Expiration, and Dihydropyridine Patent Landscape

US Patent 4,892,741 protects a press-coated, long-acting tablet containing a sparingly soluble dihydropyridine. The patent is directed to a two-stage release architecture: an immediate-release core and a surrounding slow-release coat containing additional active ingredient. The patent issued January 9, 1990, and, under the pre-Uruguay Round patent term applicable to the patent, its ordinary U.S. term expired January 9, 2007, absent an unusual extension or terminal-disclaimer issue. No current U.S. exclusionary right arises from the patent itself.[1][2]

The principal commercial relevance is historical. The claims could have covered sustained-release nifedipine, nitrendipine, nimodipine, nisoldipine, and structurally related dihydropyridines formulated as press-coated tablets. The claims do not broadly cover every extended-release dihydropyridine dosage form.

What does US Patent 4,892,741 protect?

The patent protects a specific dosage-form design rather than the dihydropyridine molecules themselves.

The core elements of independent claim 1 are:

A solid medicament preparation.
Long-lasting action.
A press-coated tablet.
A sparingly soluble dihydropyridine.
A core containing the dihydropyridine in rapid-release form.
A surrounding coat containing the dihydropyridine in slow-release form.

The claim therefore requires active ingredient in both the core and the coat. A conventional matrix tablet containing drug only in a slow-release matrix would not satisfy the literal structure of claim 1. A tablet with an immediate-release outer layer and an extended-release core would also differ from the claimed arrangement unless the claim limitations were met under an equivalents analysis.

The term "comprising" makes the claims open-ended. Additional excipients, coatings, layers, binders, lubricants, or active ingredients would not automatically avoid infringement. The accused product would still need to contain the claimed core-and-coat arrangement.

What technical problem does the patent address?

The claimed architecture is designed to combine:

An early release of drug from the core.
Continued release from the surrounding coat.
A long-lasting pharmacological effect.
Delivery of poorly water-soluble calcium-channel blockers.

The patent's technical distinction is the distribution of active ingredient between two physically different regions of a press-coated tablet. The core provides rapid release, while the coat functions as the slow-release reservoir.

How broad is independent claim 1?

Claim 1 is moderately broad at the dosage-form level but materially limited by its structure.

Limitation	Scope
Active pharmaceutical ingredient	Sparingly soluble dihydropyridine
Dosage form	Press-coated tablet
Core	Contains dihydropyridine in rapid-release form
Coat	Surrounds core and contains dihydropyridine in slow-release form
Release profile	Initial rapid release followed by sustained release
Excipients	Not restricted in claim 1
Active distribution	Required in both core and coat

The claim does not specify:

A particular drug-to-excipient ratio.
A particular tablet weight.
A particular dissolution profile.
A particular polymer.
A particular manufacturing equipment configuration.
A particular tablet shape.
A particular dose strength.

Those limitations appear in dependent claims or in the process claim.

The phrase "rapid-release form" and "slow-release form" would likely be interpreted in view of the specification, examples, dissolution testing, and the ordinary meaning of release behavior in pharmaceutical formulation practice. A product could present claim-construction risk if its core and coat have overlapping release rates or if the alleged slow-release coat does not materially delay release.

What compounds fall within claim 2?

Claim 2 adds a chemical Markush definition for the dihydropyridine. It covers substituted dihydropyridine structures with permissible groups at the R1 through R6 positions, including:

Nitro substituents.
Halogen substituents.
Trifluoromethyl substituents.
Alkyl ester groups.
Alkoxy-substituted alkyl groups.
Fluorinated alkyl groups.
Lactone-containing structures.

The chemical language is broader than the named compounds in claim 9. Claim 9 specifically identifies:

Nifedipine.
Nitrendipine.
Nimodipine.
Nisoldipine.

A product containing one of those named compounds may fall within claim 9 if it also satisfies the press-coated, dual-release structure of claim 1. Claim 9 does not independently cover the active ingredient as a compound, nor does it cover every dosage form containing those drugs.

Does claim 2 cover amlodipine?

The claim language supplied does not establish that amlodipine falls within the claimed Markush formula. Amlodipine has a distinct substituted dihydropyridine structure and should not be treated as covered solely because it is a dihydropyridine calcium-channel blocker. Chemical claim coverage must be determined by mapping the exact structure to every recited substituent and ring requirement.

How do claims 3 through 11 narrow the patent?

The dependent claims add formulation, composition, and manufacturing constraints.

Claim	Added limitation	Practical effect
3	5% to 50% of total dihydropyridine in core; 95% to 50% in coat	Broad active distribution range
4	10% to 40% in core; 90% to 60% in coat	Narrower distribution range
5	Core active is amorphous or crystalline with maximum mean particle size of 25 micrometers	Controls dissolution and dispersion
6	10% to 99% of coat weight is hydrophilic gel-forming polymer	Broad polymer-content limitation
7	Polymer is methylcellulose, HPMC, HPC, and/or sodium CMC	Closed list of specified polymers
8	Hydroxypropylcellulose is the gel-forming polymer	Narrow HPC embodiment
9	Active is nifedipine, nitrendipine, nimodipine, or nisoldipine	Named-drug limitation
10	Core includes soluble auxiliary, disintegrant, or wetting agent	Immediate-release enhancement
11	Coat has an additional rapid-release active layer	Multilayer release design

Claims 3 and 4 are alternative nested ranges. A product with 20% of its drug in the core and 80% in the coat would fall within both claims, assuming the remaining limitations are satisfied.

Claim 6 is unusually broad in polymer percentage. It recites 10% to 99% of total coat weight as hydrophilic gel-forming polymer. Claims 7 and 8 narrow the polymer identity. A formulation using polyethylene oxide, xanthan gum, carbomer, or another non-listed polymer would not literally satisfy claims 7 or 8, although claim 6 could remain relevant if the polymer qualifies as a hydrophilic gel-forming polymer.

What formulations are protected by US 4,892,741?

The strongest formulation coverage is directed to a press-coated tablet with the following profile:

A rapidly disintegrating or rapidly dissolving drug-containing core.
A surrounding coat containing most of the total active ingredient.
A hydrophilic polymer in the coat.
Drug dispersed in the coat in a slow-release matrix.
Optional outer film coating.
Optional rapid-release drug layer on the outside.

Hydroxypropylcellulose is the most specifically protected polymer under claim 8. The patent also identifies methylcellulose, hydroxypropylmethylcellulose, and sodium carboxymethylcellulose in claim 7.

The formulation claims do not expressly require a particular dissolution test result. In litigation, the release characterization would likely depend on the patent specification, prosecution history, product testing, and expert evidence. Labeling a product "extended release" would not alone prove infringement.

What manufacturing process does claim 12 protect?

Claim 12 is a process claim covering a sequence for manufacturing the press-coated tablet.

For the core, the claim recites one of several permitted routes:

Mixing active ingredient and filler.
Wet granulation with an aqueous binder solution.
Drying and sieving.
Lubricant addition.
Compression into a core.
Direct compression.
Roller compaction followed by compression.

For the coat, the claim requires:

Spraying an aqueous suspension containing active ingredient and binder onto solid ingredients.
Drying and sieving the resulting granule.
Mixing with lubricant.
Press-coating the granules around the core.

The process can include optional film coating with lacquer containing up to 20% of the total active ingredient in the final composition.

Because claim 12 is written with alternative core-production routes, a manufacturer may infringe even if it does not use wet granulation, provided it uses direct compression or roller compaction and performs the remaining claimed steps. Process infringement generally turns on the steps actually practiced, not only on the final product's composition.[3]

When did US Patent 4,892,741 expire?

Event	Date or status
U.S. patent issued	January 9, 1990
Applicable baseline term	17 years from issue for qualifying pre-June 8, 1995 patents
Ordinary expiration	January 9, 2007
Current enforceability	Expired
Current Paragraph IV relevance	None for this patent
Current Orange Book exclusivity	None arising from this patent

The patent predates the Hatch-Waxman patent-term transition that generally changed U.S. patent terms to 20 years from the earliest effective nonprovisional filing date. Under the transitional rules, patents issued before June 8, 1995 generally received the longer of the old or new term, subject to statutory exceptions. The old 17-year-from-grant term would ordinarily control where it is longer.[2]

No patent-term extension under 35 U.S.C. § 156 should be presumed from the patent number or claim set. Patent-term extension is product-specific and depends on an approved drug, regulatory review period, and statutory eligibility. The patent's ordinary expiration is sufficient to remove current infringement risk even if the historical product had regulatory delays.

What is the Orange Book status of the patent?

US Patent 4,892,741 is not a current Orange Book barrier. The Orange Book lists patents submitted by approved drug sponsors for approved products, including drug-substance, drug-product, and method-of-use patents. An expired patent does not create a current statutory delay to generic approval.[4]

The patent also appears directed to an older formulation concept rather than a current, active listed patent for a specific approved product. Orange Book status must be assessed at the product level, not from the existence of a historical patent alone.

Does the patent create a Paragraph IV risk?

No current Paragraph IV risk arises from an expired patent. A generic applicant may historically have challenged an unexpired listed patent by certifying that the patent was invalid, unenforceable, or would not be infringed. Once the patent expires, the patent no longer supports a Hatch-Waxman approval stay or delayed generic approval.

A Paragraph IV analysis for a product such as nifedipine extended release would instead focus on any later, unexpired patents covering:

A particular release profile.
A tablet geometry.
A specific polymer system.
A controlled-release manufacturing process.
A method of treating a listed indication.
A later-developed salt, particle-size distribution, or formulation.

Which companies challenged or licensed the patent?

The patent record identifies the original patent owner or assignee as Bayer-related, but the claim set itself does not establish a licensing agreement, settlement, or litigation outcome. Patent ownership, product marketing, and licensing rights may have changed after issuance.

No licensing terms can be inferred from the patent. A patent assignment does not establish a commercial license, and a marketed product does not establish that the manufacturer practiced the patent under license. Any historical litigation or settlement must be confirmed from court dockets, assignment records, and transaction disclosures.

How strong was the patent estate?

The patent was technically meaningful but narrow in claim architecture.

Strengths

Claim 1 captured the key core-and-coat product concept.
Claim 2 provided a broad chemical genus.
Claim 9 identified commercially relevant dihydropyridines.
Claims 6 through 8 covered common hydrophilic matrix polymers.
Claim 12 covered several manufacturing routes.
The open "comprising" language limited easy design-around arguments based solely on added excipients or coatings.

Weaknesses

The patent did not claim the named dihydropyridine molecules as compounds.
It did not cover every sustained-release tablet.
A product with drug only in the core or only in the surrounding matrix could avoid the central dual-location limitation.
A different dosage form, such as a capsule, osmotic system, multiparticulate system, or transdermal system, would generally fall outside the claims.
The release terms could create factual disputes.
Prior art involving immediate-release and sustained-release layers could create obviousness issues under 35 U.S.C. § 103.[5]
The patent's age makes current commercial enforcement unavailable.

The patent's strongest historical position was against a directly copied press-coated tablet using the same active distribution and hydrophilic polymer approach. Its weakest position was against modern controlled-release platforms that used different geometry, different manufacturing methods, or different drug-release mechanisms.

How does this patent compare with competing dihydropyridine patent estates?

Patent category	Typical protected subject matter	Relationship to US 4,892,741
Compound patents	Nifedipine, nimodipine, nitrendipine, nisoldipine molecules	Separate and generally earlier rights
Salt or crystal patents	Solid forms, polymorphs, salts	Potentially later and chemically distinct
Formulation patents	Matrix, multilayer, osmotic, coated, or multiparticulate systems	Potentially overlapping only if the press-coated structure is present
Method-of-use patents	Hypertension, angina, cerebral vasospasm, or other indications	Separate statutory category
Manufacturing patents	Granulation, coating, compression, or particle engineering	Claim 12 is a specific example
Device or delivery patents	Pumps, patches, implants, or specialized delivery systems	Generally outside this patent

The key freedom-to-operate question is not whether the product contains a dihydropyridine. It is whether the product uses a press-coated tablet with active ingredient in both a rapid-release core and a slow-release surrounding coat.

What generic launch scenarios existed?

For a generic product during the patent term, the principal scenarios were:

A Paragraph IV challenge asserting invalidity, unenforceability, or noninfringement.
A Paragraph III certification accepting delayed approval until expiration.
A noninfringing formulation using a different release architecture.
A licensed launch or settlement-based entry.
A product launch after patent expiration.

Today, the fifth scenario applies to this patent. A manufacturer can still face other barriers from later patents, regulatory exclusivity, trademarks, product-specific Orange Book listings, or manufacturing know-how.

Does biosimilar risk apply?

No. Nifedipine, nitrendipine, nimodipine, and nisoldipine are small-molecule drugs, not biologics. The biosimilar pathway under section 351(k) of the Public Health Service Act does not apply. Competitive entry would generally proceed through an abbreviated new drug application or another small-molecule pathway, subject to product-specific FDA requirements.[6]

What geographic coverage did the patent have?

The patent provided rights only in the United States. Foreign counterparts, if any, required separate national rights and could have had different expiration dates, claim scopes, prosecution histories, and legal status.

A U.S. product launch could therefore be free of this expired U.S. patent while foreign markets remained subject to separate formulation or manufacturing patents. Patent-family analysis requires review of the priority applications, international publication, national-phase filings, grants, lapse events, and terminal disclaimers in each jurisdiction.

Key Takeaways

US Patent 4,892,741 covers a press-coated tablet with a rapid-release dihydropyridine core and a slow-release dihydropyridine coat.
The patent potentially covered nifedipine, nitrendipine, nimodipine, and nisoldipine formulations when the claimed tablet architecture was present.
Claims 3 through 8 add active-distribution, particle-size, polymer, and composition limitations.
Claim 12 covers specified granulation, compression, coating, and press-coating manufacturing steps.
The patent issued January 9, 1990, and its ordinary U.S. term expired January 9, 2007.
The patent does not currently block generic entry, does not create a current Paragraph IV risk, and is not a current Orange Book exclusivity barrier.
The patent is not relevant to biosimilar substitution because the claimed products are small-molecule drugs.
Current freedom-to-operate analysis must focus on later patents covering specific formulations, release systems, methods of use, solid forms, or manufacturing processes.

FAQs

Can a modern nifedipine extended-release tablet infringe US 4,892,741?

Not as a matter of current U.S. patent liability because the patent has expired. Historically, infringement would have depended on whether the tablet had both a rapid-release drug-containing core and a surrounding slow-release drug-containing coat.

Does a tablet with a hydrophilic polymer automatically fall within the patent?

No. The polymer limitation is only one part of the claimed invention. The product must also satisfy the press-coated structure, dual-location active ingredient requirement, and release-function limitations.

Is a multilayer nifedipine tablet covered by claim 11?

Potentially, if it has the claim 1 core-and-coat structure and the coat is itself covered with a rapid-release active layer. A multilayer tablet that lacks the required press-coated arrangement would not necessarily fall within claim 11.

Could a capsule formulation infringe the product claims?

A capsule would generally not satisfy the express requirement for a press-coated tablet. The process claim could present a separate question only if the manufacturing steps were practiced in the claimed sequence and produced the claimed preparation.

Does expiration of US 4,892,741 eliminate all patent risk for sustained-release dihydropyridines?

No. It eliminates the enforceability of this patent, not later patents. Current risk may arise from later patents on particle size, polymorphs, matrix systems, tablet geometry, dissolution profiles, methods of use, or manufacturing processes.

References

U.S. Patent No. 4,892,741. (1990). Long-acting dihydropyridine preparation. United States Patent and Trademark Office.
United States Patent and Trademark Office. (n.d.). Patent term calculator. https://www.uspto.gov/patents/laws/patent-term-calculator
35 U.S.C. § 271. (2024). Infringement of patent.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book. https://www.fda.gov/drugsatfda
35 U.S.C. § 103. (2024). Conditions for patentability; non-obvious subject matter.
U.S. Food and Drug Administration. (2024). Abbreviated new drug application process and generic drugs. https://www.fda.gov/drugs/abbreviated-new-drug-application-anda/generic-drug-facts-labeling-and-approval-process-regulatory-information

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Germany	3720751	Jun 24, 1987

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	75142	⤷ Start Trial
Canada	1309951	⤷ Start Trial
Germany	3720757	⤷ Start Trial
Germany	3870338	⤷ Start Trial
European Patent Office	0299211	⤷ Start Trial
Spain	2051800	⤷ Start Trial
Greece	3004448	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 4,892,741

Summary for Patent: 4,892,741