United States Patent 5,364,620: Scope, Claim Construction, Expiration, and Diltiazem Patent Landscape

U.S. Patent No. 5,364,620 covers once-daily therapeutic use of a delayed-absorption diltiazem formulation for hypertension and angina. The formulation must use diltiazem-containing pellets, an organic acid, a specific acid-to-drug ratio, and a multilayer polymer membrane containing predominantly water-insoluble polymer and a lesser amount of water-soluble polymer. The patent issued on November 15, 1994, and its original 17-year patent term therefore expired in November 2011, absent an unusual term adjustment or other extension. The claims are no longer enforceable against current generic products.

What does U.S. Patent 5,364,620 protect?

The patent protects method-of-treatment claims rather than a broad composition claim. A potentially infringing product would need to be administered in the claimed clinical manner and use a formulation with the specified pellet and coating architecture.

The independent claims are claims 1 and 4:

Claim	Disease or use	Required dosing	Pharmacokinetic or pharmacodynamic limitation	Required formulation
1	Mild to moderate hypertension	Once daily	Blood-pressure-lowering peak 6 to 18 hours after administration; effect throughout 24 hours	Diltiazem pellets, organic acid, 20:1 to 1:1 drug-to-acid ratio, multilayer polymer membrane
4	Angina pectoris	Once daily	Myocardial oxygenating peak 6 to 18 hours after administration; effect throughout 24 hours	Same pellet, acid-ratio, and membrane requirements

Claims 2 and 5 add an immediate-release diltiazem component that produces an effective response within one hour. Claims 3 and 6 limit that rapid-release component to no more than approximately 25% by weight.

The patent therefore combines four claim categories:

A delayed or controlled absorption profile.
A once-daily therapeutic regimen.
A multiparticulate pellet formulation.
A defined polymer membrane and organic-acid composition.

A product that satisfies only the formulation limitations, but is not used according to the claimed hypertension or angina regimen, would not literally satisfy the method claims.

How should claim 1 be construed?

Claim 1 is a narrow combination claim. Each limitation must be present for literal infringement.

Disease and patient population

The claim is directed to a subject suffering from mild to moderate hypertension. A formulation marketed for severe hypertension, heart failure, arrhythmia, or another indication would not automatically satisfy this limitation. The relevant issue would be the actual approved labeling, promotional conduct, prescribing instructions, or other evidence of the accused use.

Once-daily administration

The claim requires administration on a once-per-day basis. A twice-daily diltiazem product would not literally meet this limitation, even if its total daily dose and blood concentration profile were similar.

The limitation also creates potential enforcement complexity. A manufacturer generally does not administer the drug itself. In a method-of-treatment case, the patentee would need to establish infringement by prescribers, patients, or another legally relevant actor, together with the manufacturer’s inducement or contributory-infringement conduct.

Twenty-four-hour control

The dose must be effective to lower blood pressure throughout the 24-hour period. This is a therapeutic-performance limitation, not merely a formulation limitation. Evidence could include pharmacokinetic data, ambulatory blood-pressure monitoring, clinical studies, labeling, or instructions for use.

The phrase does not necessarily require a perfectly flat plasma concentration curve. It requires an effect lasting through the claimed daily interval.

Peak effect 6 to 18 hours after administration

The formulation must provide peak blood-pressure-lowering levels in blood 6 to 18 hours after dosing. This limitation distinguishes the claimed product from conventional immediate-release or early-release sustained-release systems.

The language raises several construction issues:

Whether “peak” refers to plasma diltiazem concentration or the pharmacodynamic blood-pressure effect.
Whether the peak must occur within the entire 6-to-18-hour range for every patient.
Whether a product with multiple peaks satisfies the limitation.
Whether the relevant measurement is the active drug, a metabolite, or a clinical response.

A generic applicant could attempt to avoid the claim by demonstrating that its principal therapeutic peak occurs before six hours or after 18 hours. That strategy would require reliable comparative data because courts generally analyze the full claim language and the accused product’s actual characteristics.

What formulation structure is required?

The patent requires pellets with a specific core and membrane structure.

Diltiazem and organic acid

The pellet core must contain diltiazem or a pharmaceutically acceptable salt in association with an organic acid. The diltiazem component and organic acid must be present at a ratio of approximately 20:1 to 1:1.

The ratio is a substantial limitation. A formulation with a drug-to-acid ratio above approximately 20:1 or below approximately 1:1 would present a literal-infringement defense, subject to the interpretation of “about” and the evidentiary tolerance permitted by the specification.

The claim does not identify a single mandatory organic acid. The specification and prosecution history would be important in determining whether the term covers acids such as fumaric, citric, tartaric, succinic, or other pharmaceutically acceptable organic acids.

Multilayer membrane

The pellets must be surrounded by a multilayer membrane. The membrane must contain:

A major proportion of a pharmaceutically acceptable film-forming, water-insoluble synthetic polymer; and
A minor proportion of a pharmaceutically acceptable film-forming, water-soluble synthetic polymer.

This limitation is more specific than a general “controlled-release coating.” A single-layer coating, a membrane consisting only of an insoluble polymer, or a membrane using only a water-soluble polymer may fall outside the literal language.

The claim also requires relative proportions, not merely the presence of both polymer types. The patent does not set a precise numerical boundary for “major” and “minor” in the claim text supplied. The specification, examples, prosecution history, and expert testimony would likely determine those boundaries.

What do claims 2 and 3 add?

Claim 2 requires a rapid-release diltiazem portion capable of producing an effective blood-pressure-lowering amount within one hour. Claim 3 limits that rapid-release portion to up to approximately 25% by weight.

These dependent claims create a biphasic delivery profile:

An early diltiazem release for initial therapeutic effect.
A delayed or controlled release from coated pellets for later-day coverage.

Claim 3 does not require exactly 25%. It establishes an upper limit, subject to the interpretation of “about” and the method used to calculate weight percentage. Important questions include whether the percentage is calculated against total capsule weight, total diltiazem content, or active and inactive ingredients together.

How do claims 4 through 6 differ from the hypertension claims?

Claims 4 through 6 apply the same formulation architecture to angina pectoris.

Hypertension claims	Angina claims
Blood-pressure lowering	Improved myocardial blood supply and oxygen supply
Peak blood-pressure-lowering levels 6 to 18 hours after administration	Peak myocardium-oxygenating levels 6 to 18 hours after administration
Mild to moderate hypertension	Angina pectoris
Claims 2 and 3 address rapid blood-pressure response	Claims 5 and 6 address rapid myocardial oxygenation

The angina language may present greater proof issues than the hypertension language. “Myocardium oxygenating levels” is a functional therapeutic limitation that may require clinical or physiological evidence. The claim does not merely require reduced angina symptoms; it requires the formulation to improve blood supply and oxygen supply to the myocardium throughout 24 hours.

When did U.S. Patent 5,364,620 expire?

The patent issued on November 15, 1994. For a U.S. utility patent subject to the pre-Uruguay Round patent-term rule, the basic term was 17 years from issuance. On that basis, the patent expired in November 2011. The current U.S. patent term framework generally uses 20 years from the earliest effective nonprovisional filing date, but older patents such as this one are governed by the transitional rules in 35 U.S.C. § 154(c) (U.S. Patent and Trademark Office [USPTO], n.d.-b).

Milestone	Date or status
Patent issued	November 15, 1994
Basic pre-1995 term	17 years from issuance
Expected expiration	November 2011
Current status	Expired
Current enforceability	No prospective infringement enforcement based solely on this patent

The patent’s expiration removes the practical value of a current Paragraph IV challenge directed solely to this patent. A Paragraph IV certification is relevant to an unexpired Orange Book-listed patent. An expired patent cannot ordinarily support a future generic-entry block.

What was the Orange Book status of the patent?

U.S. Patent No. 5,364,620 is not a current exclusivity barrier for diltiazem products. Orange Book relevance depends on whether a patent is listed for a specific approved drug product and whether it remains unexpired. The FDA Orange Book identifies patents and regulatory exclusivity associated with approved small-molecule products, but listing is product-specific and does not itself establish infringement (FDA, n.d.-a).

The patent’s method-of-treatment format also limits its Orange Book significance. FDA patent listings for approved products can include method-of-use patents, but the listed use must correspond to the approved labeling. A patent directed to a particular delayed-absorption architecture may be difficult to list or enforce against a product whose labeling does not practice the claimed indication or dosing method.

No current FDA exclusivity period should be attributed to this patent. Diltiazem is an old small-molecule active ingredient, and the relevant regulatory competition is generic competition involving immediate-release and extended-release dosage forms.

Which diltiazem products are relevant to the patent landscape?

Diltiazem has been marketed in multiple dosage forms and release technologies. The principal competitive categories are:

Product category	Typical release concept	Relevance to Patent 5,364,620
Immediate-release tablets or capsules	Rapid systemic exposure, repeated daily dosing	Generally outside the once-daily delayed-peak combination
Extended-release capsules	Sustained or controlled release, often multiparticulate	Potentially relevant depending on pellet and membrane design
Once-daily controlled-release capsules	Delayed or prolonged exposure	Most commercially relevant category
Extended-release tablets	Matrix or osmotic delivery systems	Potentially outside the required pellet architecture
Hospital or acute-care formulations	Short-term or parenteral use	Generally outside the claimed outpatient regimen

Diltiazem hydrochloride extended-release capsules have been approved through abbreviated new drug applications and were marketed by multiple generic manufacturers. FDA product labeling identifies the dosage form, strength, release characteristics, indications, and administration frequency, but the label generally does not disclose all polymer-layer compositions or organic-acid ratios (FDA, n.d.-b).

How strong was the patent estate?

Patent 5,364,620 had meaningful technical specificity but limited breadth.

Strengths

It claims a complete therapeutic and formulation combination.
The once-daily regimen and 6-to-18-hour peak requirement distinguish it from conventional immediate-release diltiazem.
The organic-acid ratio provides a measurable compositional limitation.
The multilayer membrane requirement can be tested through formulation analysis.
Claims 2, 3, 5, and 6 add a rapid-release component that could support a biphasic product strategy.

Weaknesses

The patent claims methods, not the broad commercial composition.
The claims require particular clinical indications.
“Major proportion,” “minor proportion,” “effective,” and “about” introduce construction and proof issues.
Competitors could design around the pellet structure, polymer system, acid ratio, release timing, or dosing schedule.
The patent’s term ended in 2011.
The claims do not necessarily cover all extended-release diltiazem products.

The estate was therefore strongest against a product that copied the patented pellet architecture and was marketed for once-daily hypertension or angina treatment with the specified delayed peak. It was weaker against tablets, non-pellet capsules, alternate polymer systems, different acid ratios, or products with materially different pharmacodynamic timing.

What generic entry risks existed?

Before expiration, generic applicants could have pursued several design-around strategies:

Use a matrix tablet rather than coated pellets.
Use pellets without an organic acid.
Use an acid-to-diltiazem ratio outside the claimed range.
Use a single-layer membrane.
Use different proportions of water-soluble and water-insoluble polymers.
Produce a principal therapeutic peak outside the 6-to-18-hour window.
Avoid an immediate-release fraction.
Market dosing instructions that do not practice the claimed once-daily indication.

An ANDA applicant seeking approval for a product that referenced a listed drug with this patent listed in the Orange Book could have submitted a Paragraph IV certification alleging invalidity, unenforceability, or non-infringement. The Hatch-Waxman framework can trigger patent litigation and a 30-month approval stay when the statutory conditions are met (21 U.S.C. § 355; FDA, n.d.-a). That framework is now historical for this patent because the patent term has ended.

What litigation or settlement issues affect the patent?

The patent does not create a current litigation obstacle because it is expired. Historical litigation analysis would require review of:

Orange Book patent listings for the relevant diltiazem reference product.
ANDA Paragraph IV notices.
District court complaints under 35 U.S.C. § 271(e)(2).
Claim-construction decisions.
Any consent judgment, license, or launch-at-risk agreement.
Federal Circuit decisions addressing validity, infringement, or enforceability.

An expired patent can remain relevant to historical damages, past launch timing, and settlement analysis, but it cannot ordinarily support a new injunction against a current generic launch. A settlement agreement could still contain contractual provisions, but those provisions would not extend the statutory patent term.

How does Patent 5,364,620 compare with broader diltiazem patents?

The diltiazem landscape includes several patent families directed to different subject matter:

Patent category	Typical claim focus	Relationship to Patent 5,364,620
Active-ingredient patents	Diltiazem molecule or salt	Generally expired substantially earlier
Immediate-release formulations	Tablets, capsules, or dosage forms	Usually different release profile
Sustained-release compositions	Matrix or coated delivery systems	May overlap functionally but not structurally
Multiparticulate formulations	Pellets, beads, layered particles	Closest technical overlap
Method-of-use patents	Hypertension, angina, or cardiovascular treatment	Closest legal overlap when paired with once-daily use
Manufacturing patents	Coating, pellet formation, or process controls	May create separate manufacturing barriers
Product-specific patents	Particular branded extended-release products	Scope depends on the listed formulation and claims

A freedom-to-operate review should not rely on Patent 5,364,620 alone. It should separately assess formulation, process, crystalline-form, device, labeling, and product-specific patents for the relevant diltiazem reference product and jurisdiction.

What is the current commercial exposure?

Patent 5,364,620 has no current forward-looking revenue exclusion value because it expired in 2011. Its commercial significance is historical. During its enforceable term, the patent could have affected once-daily extended-release diltiazem products, particularly those using coated pellets and delayed pharmacodynamic release.

Current commercial exposure instead depends on:

Generic pricing and reimbursement.
Reference-product market share.
FDA approval of extended-release dosage forms.
Substitution rules.
Manufacturing capacity.
Product-specific patents that may have existed separately.
Regulatory exclusivity, if any, associated with a later product or formulation.

Diltiazem is not a biologic, so biosimilar approval pathways do not apply. The relevant FDA route is the ANDA pathway for pharmaceutically equivalent generic products, or, for certain products without a suitable reference product, an NDA pathway.

Key Takeaways

U.S. Patent 5,364,620 claims a method of treating hypertension or angina with once-daily controlled-absorption diltiazem.
The required formulation uses pellets, diltiazem plus an organic acid at approximately a 20:1 to 1:1 ratio, and a multilayer membrane containing mostly water-insoluble polymer and a lesser amount of water-soluble polymer.
The claimed therapeutic peak must occur 6 to 18 hours after administration, with activity throughout 24 hours.
Dependent claims add an immediate-release diltiazem fraction, capped at approximately 25% by weight.
The patent issued on November 15, 1994, and expired in November 2011 under the pre-1995 17-year patent-term rule.
It is not a current barrier to generic diltiazem entry.
The claims were technically specific and potentially narrow enough to design around through alternate pellet, polymer, acid-ratio, or release-profile technologies.
Biosimilar risk is irrelevant because diltiazem is a small-molecule drug.
Current competition is governed primarily by FDA approval, formulation manufacturing capability, pricing, and any separate unexpired patents, not by Patent 5,364,620.

FAQs

Does Patent 5,364,620 cover all once-daily diltiazem products?

No. It requires a specific pellet architecture, organic-acid ratio, multilayer polymer membrane, delayed peak, and therapeutic use. Matrix tablets and other extended-release systems may fall outside the claims.

Can a generic diltiazem manufacturer still be sued under Patent 5,364,620?

The patent expired in 2011. It cannot ordinarily support a new patent-infringement injunction or block current generic entry.

Does the patent cover Cardizem CD or Tiazac by name?

No. The claims do not name a brand. Coverage depends on whether a particular product and its labeled use satisfy every claim limitation.

Is the 25% rapid-release limitation required by claim 1?

No. Claim 1 does not require a rapid-release fraction. That limitation appears in dependent claims 2 and 3 for hypertension and claims 5 and 6 for angina.

Does the patent protect the diltiazem molecule itself?

No. It protects a therapeutic method using a defined controlled-absorption formulation. It does not claim diltiazem as a chemical compound.

References

Food and Drug Administration. (n.d.-a). Approved drug products with therapeutic equivalence evaluations: Orange Book. U.S. Department of Health and Human Services.
Food and Drug Administration. (n.d.-b). Diltiazem hydrochloride extended-release capsules: Prescribing information. U.S. Department of Health and Human Services.
U.S. Patent and Trademark Office. (n.d.-a). U.S. Patent No. 5,364,620. U.S. Department of Commerce.
U.S. Patent and Trademark Office. (n.d.-b). Patent term adjustment and patent term provisions under 35 U.S.C. § 154. U.S. Department of Commerce.
21 U.S.C. § 355. (2024). New drugs.
35 U.S.C. § 154. (2024). Contents and term of patent; provisional rights.
35 U.S.C. § 271(e)(2). (2024). Infringement of patents relating to regulated products.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	241987	⤷ Start Trial
Austria	66813	⤷ Start Trial
Australia	2377588	⤷ Start Trial
Australia	615221	⤷ Start Trial
Australia	634660	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 5,364,620

Summary for Patent: 5,364,620