United States Drug Patent 4,849,226: Claim Scope, Expiration, Litigation Risk, and Nitroglycerin Patch Patent Landscape

U.S. Patent No. 4,849,226 protects a transdermal method for increasing myocardial oxygen supply by administering a vasodilator, principally nitroglycerin, from a specific multilayer medical bandage. The patent is expired. Its ordinary 17-year term ended on July 18, 2006, assuming no terminal disclaimer or unusual term adjustment. The claims no longer create a current U.S. patent barrier to generic nitroglycerin patches, although the patent remains relevant for historical freedom-to-operate analysis, claim construction, and prior-art review.

What does U.S. Patent 4,849,226 protect?

The patent is a method patent directed to transdermal administration of a vasodilator to increase oxygen delivery to the heart. It does not claim nitroglycerin as a chemical compound. It claims the use of a particular bandage or patch architecture to administer the drug.

Claim 1 requires all of the following:

A warm-blooded animal with symptoms indicating interference with oxygen supply.
Administration of a vasodilator.
Topical administration from a medical bandage.
A substantially drug-impermeable backing member.
A reservoir containing:
- a gelled fluid;
- a rheological agent; and
- a vasodilator capable of dilating arteries and arterioles.
A rate-controlling membrane that governs vasodilator release.
Administration of a therapeutically effective amount.
An increase in the oxygen supply to the heart.

The claim is therefore narrower than a generic claim covering any nitroglycerin patch. It requires a reservoir-based transdermal system with specified structural and functional components.

What is the central inventive concept?

The central concept is controlled transdermal delivery of a vasodilator through a gelled reservoir and rate-controlling membrane. The backing limits drug loss away from the skin, while the membrane regulates drug passage toward the skin.

The claim combines:

therapeutic purpose;
route of administration;
patch construction;
reservoir composition;
membrane-controlled release; and
a dosage result.

This combination limits the claim’s reach. A product that delivers nitroglycerin through a different architecture, such as a drug-in-adhesive system without the claimed gelled reservoir, would not necessarily satisfy every limitation.

How do claims 2 through 14 narrow claim 1?

The dependent claims add specific material, dosage, patient, and packaging limitations.

Claim	Additional limitation	Practical significance
2	Gelled silicone fluid	Narrows the reservoir vehicle
3	Silicon dioxide as rheological agent	Requires a specified thickening or rheological component
4	Fumed or colloidal silicon dioxide	Further narrows the silicon dioxide limitation
5	Ethylene-vinyl acetate membrane	Requires EVA as the rate-controlling membrane
6	Polyethylene, aluminized PET, and EVA backing layers	Specifies a multilayer backing construction
7	Aluminized PET, ionomer, and EVA backing layers	Provides an alternative specified backing construction
8	Adhesive on the rate-controlling membrane	Requires an adhesive arrangement for skin retention
9	Human patient and systemic transdermal entry	Focuses the claim on human systemic delivery
10	Sealed backing and 10 to 2,000 micrograms per hour	Adds sealing and broad delivery-rate limitations
11	Nitroglycerin as the vasodilator	Limits the active ingredient
12	Nitroglycerin at 20 to 1,200 micrograms per hour	Narrows the dose-rate range
13	Adhesive and peelable protective liner	Adds a conventional patch-application structure
14	Therapeutically effective priming amount	Requires an initial loading or priming dose

Claims 11 and 12 are commercially the most important because they connect the broad vasodilator concept to nitroglycerin, the active ingredient used in historical transdermal angina products.

What is the patent expiration date for U.S. Patent 4,849,226?

The patent issued on July 18, 1989. For a U.S. patent subject to the pre-1995 term rule, the statutory term was generally 17 years from grant. On that basis, the patent expired on July 18, 2006. The term framework is governed by 35 U.S.C. § 154 as amended by the Uruguay Round Agreements Act, with older patents generally retaining the applicable pre-change term rules.

Event	Date
Patent grant	July 18, 1989
Ordinary 17-year expiration	July 18, 2006
Current enforceability	Expired
Current Paragraph IV blocking risk	None from this patent

The patent cannot support a new infringement action for post-expiration activity. It may still be cited as prior art against later patent applications, subject to the relevant prior-art rules.

What is the claim scope of the nitroglycerin claims?

Claim 11 covers the method of claim 1 when the vasodilator is nitroglycerin. Claim 12 further requires a nitroglycerin delivery rate of 20 to 1,200 micrograms per hour.

The claim does not require every commercial nitroglycerin patch to infringe. A potentially infringing product would need to practice the required method using a bandage with the claimed reservoir and membrane configuration. Key limitations include:

a gelled fluid reservoir;
a rheological agent;
a vasodilator in the reservoir;
a substantially impermeable backing;
a rate-controlling membrane; and
topical use for increasing oxygen supply to the heart.

The phrase "increasing the supply of oxygen to the heart" is a therapeutic-purpose limitation. In a method claim, the accused use and instructions for use would be relevant. A patch used for a different purpose, or without the required therapeutic intent, could present a different infringement analysis, although product labeling and actual use would matter.

How strong was the patent estate for the transdermal nitroglycerin patch?

The patent was technically specific but commercially meaningful during its term. Its strongest features were the combination of:

a silicone-based gel reservoir;
silicon dioxide rheology control;
an EVA rate-controlling membrane;
impermeable multilayer backing;
adhesive attachment; and
controlled nitroglycerin release.

Its weaknesses were equally important:

Method-only protection. The patent did not claim the nitroglycerin molecule or every patch configuration.
Multiple structural limitations. A competitor could avoid infringement by changing the reservoir, membrane, backing, or drug-in-adhesive design.
Functional therapeutic limitation. The claim required use to increase cardiac oxygen supply.
Narrow dependent claims. Claims 2 through 7 and 10 through 13 require specific materials or rate ranges.
Expiration. All exclusionary value ended in 2006.

The broadest commercial risk was likely associated with products using the same reservoir-and-membrane architecture rather than with all transdermal nitroglycerin products.

What formulations are protected by the patent?

The patent’s formulation coverage centers on a gelled fluid containing a vasodilator and a rheological agent.

Gelled silicone fluid

Claim 2 limits the gelled fluid to silicone fluid. Silicone-based systems can provide stable drug dispersion and controlled transport through a membrane.

Silicon dioxide rheological agent

Claim 3 requires silicon dioxide. Claim 4 identifies fumed silicon dioxide and colloidal silicon dioxide. These materials increase viscosity and help maintain the physical structure of the gel reservoir.

EVA membrane

Claim 5 requires ethylene-vinyl acetate copolymer as the rate-controlling membrane. EVA was widely used in transdermal delivery because its permeability can be modified through polymer composition and thickness.

Multilayer backing

Claims 6 and 7 protect alternative laminate structures using combinations of polyethylene, aluminized polyethylene terephthalate, ionomer, and EVA. These layers perform barrier, mechanical, sealing, and drug-retention functions.

Adhesive and liner

Claims 8 and 13 add skin adhesive and a removable protective liner. These limitations describe the patch’s application and handling system rather than the active pharmaceutical ingredient itself.

Did the patent protect a particular dose or delivery rate?

Yes. Claim 10 covers a therapeutically effective delivery rate of approximately 10 to 2,000 micrograms per hour. Claim 12 narrows nitroglycerin delivery to 20 to 1,200 micrograms per hour.

These ranges are broad enough to encompass many historical transdermal nitroglycerin products. They do not, however, independently establish infringement. The patch must also satisfy the reservoir, membrane, backing, and therapeutic-use limitations.

The inclusion of a "priming amount" in claim 14 indicates an initial loading phase intended to reach therapeutic systemic concentrations more quickly. A patch using only constant-rate delivery without a distinct priming amount may avoid that dependent claim.

What was the FDA and Orange Book relevance?

The patent was relevant to transdermal nitroglycerin products regulated as prescription drugs. Nitroglycerin patches are small-molecule drug products, not biologics. FDA approval would generally proceed through an NDA for an innovator product and an ANDA for a therapeutically equivalent generic product.

The Orange Book identifies approved drug products, therapeutic-equivalence evaluations, patent information submitted for listed products, and exclusivity information. Orange Book listing does not extend an expired patent and does not independently establish patent validity or infringement. FDA’s publication of a patent in the Orange Book is an administrative listing that interacts with the ANDA Paragraph IV process under the Hatch-Waxman Act. [2][3]

For an expired 1989 patent, the practical regulatory consequence is limited:

it cannot trigger a current 30-month stay;
it cannot support a current Paragraph IV litigation strategy;
it does not prevent ANDA approval;
it does not create current market exclusivity; and
it does not create biosimilar exclusivity because nitroglycerin is not a biologic.

When did generic manufacturers face Paragraph IV risk?

During the patent’s term, an ANDA applicant seeking approval before expiration could have faced a Paragraph IV certification if the patent was listed against the relevant reference product. A Paragraph IV certification asserts that a listed patent is invalid, unenforceable, or will not be infringed by the proposed generic product. The reference-product sponsor could then bring patent litigation, potentially triggering the statutory 30-month stay under 21 U.S.C. § 355(j)(5)(B)(iii).

That risk ended when the patent expired in 2006. Any current generic applicant faces formulation, bioequivalence, manufacturing, labeling, and regulatory issues, but not a live exclusionary right under U.S. Patent 4,849,226.

Which companies challenged or commercialized nitroglycerin patches?

The historical transdermal nitroglycerin market included branded and generic products associated with companies such as:

Key Pharmaceuticals and Schering-Plough, associated with Nitro-Dur;
Ciba-Geigy and Novartis, associated with Transderm-Nitro;
3M and other transdermal technology suppliers;
Mylan and other generic manufacturers;
Watson Pharmaceuticals, later Actavis;
Sandoz and other generic or authorized-generic suppliers.

The precise patent position of each company depended on the formulation, delivery platform, reference product, ANDA certification, licensing arrangements, and settlement terms. Publicly available evidence does not establish that every historical manufacturer licensed or challenged U.S. Patent 4,849,226 specifically.

What litigation and settlement exposure remains?

No active enforcement exposure remains under this patent because it expired in 2006. A historical litigation search should distinguish among:

infringement suits involving this patent;
suits involving related transdermal-system patents;
ANDA litigation involving nitroglycerin reference products;
patent term or terminal-disclaimer issues; and
settlements covering broader product portfolios.

A settlement concerning another nitroglycerin patch patent would not establish that U.S. Patent 4,849,226 was asserted or licensed. The patent number must be matched directly to the complaint, answer, docket, or settlement agreement.

How does this patent compare with later transdermal patch patents?

U.S. Patent 4,849,226 is an early reservoir-system patent. Later transdermal patents commonly shifted toward:

drug-in-adhesive systems;
multilayer adhesive matrices;
permeation enhancers;
reduced skin irritation;
improved adhesion;
rate-control through polymer composition;
dosing schedules and wear-time improvements; and
manufacturing and packaging controls.

A later product may avoid the expired patent while still being covered by later patents directed to adhesive chemistry, manufacturing methods, packaging, or a specific formulation. The expiration of 4,849,226 therefore removes one historical barrier but does not prove that every later transdermal nitroglycerin product is free of all patent constraints.

What generic launch risks exist today?

The patent-specific launch risk is zero because the patent is expired. Current commercial risks are more likely to involve:

FDA demonstration of bioequivalence;
residual nitroglycerin stability;
patch adhesion and wear performance;
dose-rate reproducibility;
packaging against drug loss and evaporation;
nitroglycerin handling and worker safety;
reference-product sourcing;
market size and reimbursement;
manufacturing scale; and
later patents held by suppliers or competitors.

Nitroglycerin is an established small molecule with extensive historical use. The principal barriers are regulatory execution and reliable transdermal manufacturing, not the expired patent.

Key Takeaways

U.S. Patent 4,849,226 claims a method of increasing cardiac oxygen supply using a transdermal vasodilator patch.
The patent’s core architecture is a gelled reservoir, rheological agent, rate-controlling membrane, and drug-impermeable backing.
Claims 11 and 12 specifically cover nitroglycerin and defined delivery-rate ranges.
Dependent claims identify silicone gel, silicon dioxide, EVA, multilayer backing, adhesive, liner, and priming-dose features.
The patent issued July 18, 1989, and its ordinary term ended July 18, 2006.
It creates no current Paragraph IV, Orange Book, generic-launch, or biosimilar barrier.
The patent was narrower than a product claim covering all nitroglycerin patches.
Current risk is more likely to arise from later formulation, adhesive, manufacturing, packaging, or regulatory requirements.

FAQs

Is U.S. Patent 4,849,226 still enforceable?

No. Its ordinary U.S. patent term expired on July 18, 2006.

Does the patent cover all nitroglycerin patches?

No. It requires a specific reservoir-based patch configuration and a method of increasing oxygen supply to the heart.

Is nitroglycerin eligible for biosimilar competition?

No. Nitroglycerin is a chemically synthesized small-molecule drug. Generic competition proceeds through the ANDA pathway, not the biosimilar pathway.

Could a drug-in-adhesive nitroglycerin patch infringe the patent?

A drug-in-adhesive patch may avoid infringement if it lacks the claimed gelled reservoir and rate-controlling membrane. In any event, the patent is expired.

Does expiration of this patent eliminate all patent risk for a new nitroglycerin patch?

No. Later patents may cover adhesive systems, formulations, manufacturing processes, packaging, dosing methods, or other product features.

References

U.S. Patent No. 4,849,226. (1989). United States Patent and Trademark Office.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations. FDA.
U.S. Food and Drug Administration. (2024). Orange Book: Questions and answers. FDA.
21 U.S.C. § 355(j). Abbreviated applications for new drugs.
35 U.S.C. § 154. Contents and term of patents; provisional rights.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	229476	⤷ Start Trial
Austria	395815	⤷ Start Trial
Austria	A84882	⤷ Start Trial
Australia	545402	⤷ Start Trial
Australia	7921282	⤷ Start Trial
Belgium	893394	⤷ Start Trial
Canada	1164749	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 4,849,226

Summary for Patent: 4,849,226