U.S. Patent 4,863,742: Verapamil Controlled-Release Pellet Claims, Expiration, and Patent Landscape

U.S. Patent No. 4,863,742 protects a multiparticulate, once-daily verapamil formulation built around acid-containing pellets, layered polymer cores, and multilayer release membranes. Its principal protection is formulation-specific, not molecule-specific. The patent expired in 2006, so none of its claims currently creates an enforceable U.S. barrier to generic verapamil products. The claims remain relevant as prior art and as a technical reference for extended-release verapamil design. [1]

What invention does U.S. Patent 4,863,742 protect?

The patent covers controlled-absorption verapamil pellets designed to release drug over approximately 24 hours. The claimed technology combines five principal elements:

Verapamil or a pharmaceutically acceptable salt, particularly verapamil hydrochloride.
An organic acid in the pellet core.
A layered polymeric core containing predominantly water-soluble polymer and a smaller amount of water-insoluble polymer.
A multilayer membrane containing predominantly water-insoluble film-forming polymer and a smaller amount of water-soluble polymer.
A defined pharmacokinetic or dissolution profile.

The patent’s central technical objective is to reduce the impact of gastrointestinal pH on verapamil release while producing once-daily exposure.

The independent formulation claims are claims 1 and 3. Claim 1 is defined principally by an in-vivo pharmacokinetic result, while claim 3 is defined principally by an in-vitro dissolution profile.

Independent claim	Primary limitation	Performance requirement
Claim 1	Layered acid-containing verapamil core plus multilayer membrane	24-hour controlled absorption; in-vivo Tmax of 6 to 16 hours
Claim 3	Similar pellet architecture	Substantially pH-independent dissolution meeting five time-point ranges
Claim 30	Manufacturing process	Forming the core and applying a release-controlling polymer membrane
Claim 31	Blend formulation	Controlled-release pellets plus rapid-release pellets
Claim 32	Blend formulation with dissolution limits	Immediate component plus controlled-release component
Claims 37-38	Therapeutic methods	Once-daily treatment of hypertension or angina

How broad are the claims of U.S. Patent 4,863,742?

The claims are technically detailed but commercially narrower than a general extended-release verapamil claim. A potentially infringing product would need to satisfy the required combination of composition, pellet structure, membrane architecture, and functional performance.

Claim 1: in-vivo controlled absorption

Claim 1 requires a pellet with:

Verapamil or a pharmaceutically acceptable salt.
One or more listed organic acids.
A core made from superimposed layers of drug-acid powder and polymeric material.
A polymeric core material containing a major proportion of water-soluble polymer and a minor proportion of water-insoluble polymer.
A surrounding multilayer membrane.
A membrane containing a major proportion of water-insoluble film-forming polymer and a minor proportion of water-soluble film-forming polymer.
Drug release over 24 hours.
An in-vivo Tmax between six and 16 hours.

The acid list is closed as drafted. It includes adipic, ascorbic, citric, fumaric, malic, succinic, and tartaric acid, together with mixtures of those acids.

The claim is not limited to one specific polymer. It uses functional and proportional language, such as "major proportion," "minor proportion," "freely permeable," and "slightly permeable." Those terms create potential claim-construction disputes because the claim does not provide universal numerical thresholds for each expression.

Claim 3: in-vitro dissolution pathway

Claim 3 covers a similar pellet but replaces the principal pharmacokinetic limitation with a dissolution profile measured in potassium chloride using the USP XXI basket method at 37°C.

The required cumulative release ranges are:

Time point	Required release
1 hour	0% to 25%
4 hours	0% to 35%
8 hours	30% to 60%
11 hours	50% to 75%
24 hours	At least 80%

Claim 3 also requires release that is "substantially pH independent." This limitation is significant because a formulation could match the numerical dissolution ranges in one medium yet fail the pH-independence requirement.

Functional limitations and infringement risk

The claims combine structural and performance limitations. A product that uses an acid-containing core and a polymer membrane is not automatically within the claims. It would also need to satisfy the claimed layer arrangement and, depending on the asserted claim, the specified in-vivo or in-vitro release profile.

The principal design-around routes would include:

Excluding every acid listed in the claims.
Using a non-layered matrix rather than superimposed powder and polymer layers.
Using a single membrane rather than a multilayer membrane.
Reversing or materially changing the water-soluble and water-insoluble polymer proportions.
Using a release profile outside the claimed dissolution windows.
Producing a Tmax outside the six-to-16-hour range, subject to the other claim limitations.
Using a formulation that is not a pellet-based multiparticulate system.

Because the patent is expired, these design-around points have historical and prior-art significance rather than current infringement significance.

What dependent claims add to the patent scope?

Claims 2 and 4 through 29 narrow the formulation claims through pharmacokinetic, compositional, structural, and excipient limitations.

Pharmacokinetic and ratio limitations

Claim 2 narrows claim 1 to a Tmax of seven to 10 hours.
Claims 4 and 5 require a verapamil-to-organic-acid ratio from 1:1 to 10:1.
Claim 29 specifies verapamil hydrochloride.

The ratio limitation does not appear to require a particular acid, provided the acid is within the closed list in the relevant independent claim.

Core polymer limitations

Claims 6 through 15 narrow the polymeric core. They address:

A major proportion of polymer freely permeable to verapamil and water.
A minor proportion of polymer slightly permeable to verapamil and water.
Hydroxypropyl methylcellulose and polyvinylpyrrolidone as water-soluble polymers.
Acrylic and methacrylic acid ester copolymers as permeability-controlling materials.
Methylcellulose, ethylcellulose, propylcellulose, and shellac as water-insoluble polymers.

Claims 11, 12, 14, and 15 are particularly dependent on functional permeability characteristics rather than only on chemical identity. That creates a technical testing issue: the relevant question is not simply whether a polymer belongs to a named chemical class, but whether it has the claimed permeability behavior in the formulation.

Inert seed and pellet construction

Claims 16 through 19 require the drug, acid, and polymeric material to be built around an inert core. Claims 18 and 19 further specify a non-pareil seed with an average diameter of 0.3 to 0.7 millimeter.

This limitation targets pharmaceutical layering processes in which drug-containing coats are applied to sugar spheres or other inert starter particles.

Membrane limitations

Claims 22 through 28 narrow the membrane composition:

Shellac, cellulose acetate, or ethylcellulose as water-insoluble membrane polymers.
Polyvinylpyrrolidone, polyvinyl alcohol, or hydroxypropyl methylcellulose as water-soluble membrane polymers.
A major proportion of slightly permeable polymer and a minor proportion of freely permeable polymer.
Acrylic and methacrylic acid ester copolymers with selected permeability characteristics.
A major proportion of nonporous polymer and a minor proportion of porous polymer.

The membrane limitations are central to the patent’s release-control mechanism. A formulation using a different membrane technology, such as an osmotic system or a hydrophilic matrix without coated pellets, would generally fall outside the literal architecture of these claims.

What do claims 30 through 38 cover?

Manufacturing process claim

Claim 30 covers producing the claimed pellet by:

Forming a core containing verapamil and an organic acid.
Enclosing the core in a film-forming polymer membrane.
Selecting the membrane to provide the claimed release behavior.

The claim is less detailed than claims 1 and 3, but it remains tied to the claim 1 release architecture and performance.

Immediate-release and controlled-release blend

Claims 31 and 32 cover a combination of:

Controlled-release pellets with a multilayer membrane.
Rapid-release pellets based on the same core concept but without the multilayer membrane.

The purpose is to produce therapeutic verapamil levels within one hour while preserving prolonged release. Claims 33 and 34 limit the rapid-release component to up to 12.5% by weight.

Claims 35 and 36 extend the blend to capsules or tablets.

Method-of-use claims

Claims 37 and 38 cover once-daily administration for:

Mild to moderate hypertension.
Prevention or reduction of angina attacks.

The claimed regimen includes an initial verapamil component providing an effect within one hour and a second component providing maximum effect six to 16 hours after administration. The method claims also incorporate the up-to-12.5% rapid-release component limitation.

These are formulation-linked method claims. They do not broadly cover treating hypertension or angina with any verapamil product.

When did U.S. Patent 4,863,742 expire?

U.S. Patent 4,863,742 issued on September 5, 1989. Because it is a pre-June 8, 1995 patent, its ordinary term was 17 years from issuance. The patent therefore expired on September 5, 2006, absent an earlier terminal disclaimer or other unusual event. [1]

Event	Date
U.S. patent issued	September 5, 1989
Ordinary 17-year expiration	September 5, 2006
Current enforceability	Expired
Current patent-based generic blocking right	None

The expiration eliminates the ability to obtain damages or injunctive relief for post-expiration conduct based on these claims. The patent can still be cited as prior art against later patent applications and may remain relevant to obviousness, written-description, enablement, and claim-scope analysis.

What is the Orange Book status of the patent?

An expired patent cannot currently block FDA approval through a live Orange Book patent listing. The Orange Book distinguishes active patent information from patents that have expired or otherwise ceased to provide enforceable exclusivity. FDA’s Orange Book also separates patent protection from regulatory exclusivity, such as new chemical entity or pediatric exclusivity. [2]

For verapamil products, the relevant regulatory issue is usually the product-specific status of extended-release tablets, capsules, or pellets rather than the continuing force of U.S. Patent 4,863,742. The patent itself does not provide current Orange Book exclusivity.

A generic applicant could historically have addressed an unexpired formulation patent through a Paragraph IV certification. That mechanism is no longer commercially necessary for this patent because the patent term has ended. An ANDA applicant generally does not need to litigate an expired patent to obtain approval, although other listed patents, labeling protections, or regulatory exclusivities may still matter. [2,3]

Are Paragraph IV challenges or settlements associated with this patent?

A Paragraph IV certification is relevant only while a listed patent presents a potential approval barrier. For U.S. Patent 4,863,742, the expiration date removes the current litigation incentive associated with the patent.

The available patent record does not establish a current, enforceable Paragraph IV dispute involving this patent. Any historical litigation or settlement involving branded extended-release verapamil products would need to be separated from the status of the patent itself. A settlement involving another patent in a verapamil product family would not extend the term of U.S. Patent 4,863,742.

No settlement can revive an expired patent or create a private exclusivity period against unrelated generic manufacturers.

What products and companies were exposed to this patent?

The patent is associated with the controlled-release verapamil technology used in historical branded and licensed-product strategies. Verapamil extended-release products have been marketed in several dosage forms and under multiple brand names, including products associated with Knoll and later pharmaceutical companies.

The commercial exposure was concentrated in:

Once-daily extended-release verapamil capsules or tablets.
Multiparticulate pellet products.
Products using rapid-release and controlled-release pellet blends.
Hypertension and angina indications.

The patent did not cover immediate-release verapamil generally, injectable verapamil, or every extended-release verapamil system.

Current revenue attributable specifically to this patent is zero as a matter of enforceable patent exclusivity. Historical sales attributable to products practicing the claims cannot be calculated from the patent record alone.

How does this patent compare with other verapamil patent strategies?

Technology category	Relationship to U.S. 4,863,742	Current risk from this patent
Immediate-release verapamil tablets	Outside the pellet architecture	None
Conventional hydrophilic matrix tablet	Usually outside the layered pellet and membrane limitations	None
Multiparticulate coated pellets	Technically closest category	None because patent expired
Osmotic verapamil delivery system	Different release mechanism	None
Acid-containing verapamil pellets	Potentially similar historical technology	None because patent expired
Current generic verapamil ER product	May use a different or expired technology	No risk from this patent
New follow-on formulation patent	Separate analysis required	Depends on later patent term

The principal competitive significance of this patent is historical. It illustrates a strategy for obtaining formulation protection without claiming verapamil as a chemical entity. The patent attempted to protect the relationship among pellet construction, polymer permeability, acid selection, release profile, and clinical timing.

How strong was the patent estate?

The estate was moderately specific and technically layered.

Strengths

Independent claims covered both in-vivo and in-vitro performance.
The claims addressed the pellet core, membrane, composition, process, dosage form, and therapeutic use.
The dissolution claim provided measurable performance criteria.
The claims targeted a commercially useful once-daily profile.
Dependent claims identified common pharmaceutical polymers and inert seed sizes.

Weaknesses

The patent did not cover verapamil itself.
The architecture required multiple structural elements.
"Major proportion," "minor proportion," and permeability terms could create construction and proof disputes.
The release claims required extensive formulation and testing data.
A competing product could use a different extended-release platform.
The patent term ended in 2006.

From a historical enforcement perspective, the patent’s strongest claims were likely those supported by direct formulation matching and dissolution testing. Its weakest area was a product using a materially different pellet process or release mechanism while achieving similar clinical exposure.

What manufacturing and intellectual-property barriers remain?

No manufacturing barrier remains from this patent. The claimed materials are conventional pharmaceutical excipients, including cellulose derivatives, shellac, hydroxypropyl methylcellulose, polyvinylpyrrolidone, and acrylic or methacrylic copolymers.

The principal historical manufacturing requirements were:

Layering drug and acid onto non-pareil seeds.
Controlling pellet size and coating uniformity.
Applying multiple polymer layers.
Managing polymer permeability and membrane porosity.
Achieving the specified release profile.
Maintaining batch-to-batch dissolution consistency.

Current manufacturers may still face process patents, formulation patents, regulatory requirements, and product-specific ANDA obligations unrelated to U.S. Patent 4,863,742. Those rights must be evaluated separately from this expired patent.

What generic launch risks exist today?

The patent presents no current U.S. generic launch risk because it expired in 2006. A generic applicant’s remaining risks would arise from:

Other unexpired formulation or process patents.
Orange Book-listed patents for the specific reference product.
Product-specific labeling requirements.
Bioequivalence failure.
Dissolution-profile mismatch.
Manufacturing scale-up problems.
State of the art and later patent families.

A product that practices the exact claim architecture may be commercially launched without infringing this expired patent, assuming it satisfies all other FDA and intellectual-property requirements.

Key Takeaways

U.S. Patent 4,863,742 covers controlled-release verapamil pellets, not verapamil generally.
The core technology requires an acid-containing, layered polymer core and a multilayer release membrane.
Claim 1 uses an in-vivo Tmax limitation of six to 16 hours.
Claim 3 uses a pH-independent dissolution profile measured at one, four, eight, 11, and 24 hours.
Claims 31 through 36 cover rapid-release and controlled-release pellet blends in capsules or tablets.
Claims 37 and 38 cover once-daily treatment of hypertension and angina.
The patent expired on September 5, 2006.
It creates no current U.S. Orange Book or Paragraph IV barrier.
No biosimilar analysis applies because verapamil is a small-molecule drug, not a biologic.
Current commercial risk must be assessed against later patents, product-specific FDA listings, and formulation technologies.

FAQs

Does U.S. Patent 4,863,742 cover Verelan?

It may describe technology used in historical extended-release verapamil products, but the patent does not identify every product that may be sold under the Verelan name. The patent expired in 2006.

Can a generic manufacturer use the same verapamil pellet design?

Yes, the expired patent no longer prevents use of its claimed formulation in the United States. Other unexpired patents or regulatory requirements may still apply.

Does the patent cover verapamil hydrochloride immediate-release tablets?

No. The claims require a controlled-absorption pellet architecture and do not broadly cover immediate-release verapamil hydrochloride.

Is a 24-hour release profile alone enough to infringe the patent?

No. The claims require the specified core, polymer, membrane, acid, and performance limitations. A 24-hour profile without the claimed structural elements would not necessarily satisfy the claims.

Are biosimilar applicants relevant to this patent?

No. Verapamil is a small-molecule active ingredient. Generic-drug pathways, including ANDA and Paragraph IV procedures, are relevant; the biosimilar pathway is not.

References

United States Patent and Trademark Office. (1989). U.S. Patent No. 4,863,742: Controlled absorption verapamil formulation.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations, commonly known as the Orange Book.
U.S. Food and Drug Administration. (2024). Abbreviated new drug application regulations and patent certification requirements.

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Ireland	1661/86	Jun 20, 1986

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	72975	⤷ Start Trial
Australia	599385	⤷ Start Trial
Australia	7452887	⤷ Start Trial
Germany	3776982	⤷ Start Trial
European Patent Office	0250267	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 4,863,742

Summary for Patent: 4,863,742