United States Patent 5,160,744: Claim Scope, Expiration, Orange Book Status, and Patent Landscape

US Patent 5,160,744 protects an osmotic, delayed-release dosage form designed to administer verapamil after a drug-free interval of up to 4.5 hours. Its core combination is a drug-containing composition, a swelling push composition, a slowly hydrating semipermeable wall, and an exit passageway. The patent is associated with the ALZA osmotic delivery platform used for delayed and chronotherapeutic drug release.

The patent has expired under the ordinary pre-URAA patent-term rules. Its principal commercial value was historically linked to delayed-release verapamil products, particularly Covera-HS. It does not create current blocking exclusivity for verapamil products in the United States.

What does US Patent 5,160,744 protect?

The patent claims a multilayer osmotic dosage form that delays drug delivery and then expels the drug through an opening. Claim 1 is the principal composition claim.

Claim element	Required limitation
Drug composition	Verapamil, in an amount of 0.05 nanograms to 1.5 grams
Drug composition polymer	20 wt% to 50 wt% poly(ethylene oxide), or PEO
PEO function	Changes from a nondispensable viscosity to a dispensable viscosity when hydrated
Push composition	A fluid-imbibing, expanding polymeric composition
Wall	Permeable to environmental fluid and contains 35 wt% to 55 wt% of a slowly hydrating polymeric composition
Delivery opening	At least one exit means or passageway
Performance result	Delayed verapamil delivery for up to 4.5 hours

The claim is directed to a functional delivery system, not merely to verapamil or to a conventional sustained-release tablet. A competing product must satisfy the structural limitations and the claimed delayed-delivery behavior to present a strong literal-infringement case.

How broad is claim 1 of US Patent 5,160,744?

Claim 1 is broad in drug amount, wall architecture, and polymer identity, but narrow in its required combination of features.

Drug amount and active ingredient

The claim covers verapamil across an unusually wide concentration range, from 0.05 nanograms to 1.5 grams. The range is unlikely to be the primary commercial limitation because marketed oral verapamil doses generally fall within a much narrower therapeutic range.

The claim also requires the PEO to constitute 20 wt% to 50 wt% of the first composition. This limitation can exclude formulations that use lower PEO concentrations, substitute a different viscosity-modifying polymer, or place the PEO in a separate layer.

Push composition

The second composition must imbibe fluid, expand, and push the drug composition from the dosage form. This is characteristic of an elementary osmotic pump or push-pull osmotic system.

The claim does not require a particular grade or molecular weight of PEO in the push layer. It also does not specify every excipient, osmagent, lubricant, colorant, or coating component. The breadth therefore extends across multiple formulation recipes, provided that the push layer performs the claimed displacement function.

Wall composition

The wall must be permeable to fluid and contain 35 wt% to 55 wt% of a polymeric composition that hydrates slowly. Claim 7 narrows the wall composition by identifying hydroxypropylcellulose and cellulose acetate, cellulose diacetate, or cellulose triacetate.

A product with a rapidly hydrating wall, a fully water-soluble coating, or a wall outside the claimed composition range could avoid literal infringement of claim 1. The analysis would still depend on the complete formulation and the applicability of equivalents.

Delayed-delivery limitation

The claimed delay is not an aspirational product description. It is a claim limitation. The dosage form must provide a delayed-drug interval of up to 4.5 hours through the combined operation of the drug layer, push layer, and wall.

This creates an important proof issue. An accused product may have the same general OROS architecture but avoid the claim if its delay is materially shorter, longer, or achieved through a different mechanism. Testing under relevant gastrointestinal or dissolution conditions would likely be central to an infringement dispute.

What do claims 2 through 6 add?

Claims 2 through 6 extend or refine the coverage.

Claim	Scope
2	Calcium channel blockers and pharmaceutically acceptable derivatives
3	Named calcium channel blockers, including nifedipine, diltiazem, nimodipine, felodipine, and amlodipine
4	Verapamil and pharmaceutically acceptable salts
5	Named ACE inhibitors, including ramipril, enalapril, lisinopril, captopril, and quinapril
6	A pore-orifice as the exit means

Claims 2, 3, and 5 use “replaced by” language. Read literally, they expand the active ingredient beyond verapamil while retaining the other limitations of claim 1. Claim 5 is particularly broad because it moves outside calcium channel blockers into ACE inhibitors.

Claim 6 narrows the delivery opening to a pore-orifice. A drilled or laser-formed passageway may be treated differently from a pore formed by coating composition, osmotic erosion, or another manufacturing process, depending on the specification and prosecution history.

What does claim 7 protect?

Claim 7 is an independent method claim directed specifically to administering verapamil to the gastrointestinal tract.

It requires:

A dosage form admitted into the gastrointestinal tract.
A wall containing 35 wt% to 55 wt% hydroxypropylcellulose and a cellulose acetate family member.
A drug composition containing verapamil and 20 wt% to 50 wt% PEO.
A separate push composition containing a different PEO from the drug composition.
A passageway for drug delivery.
A transition from a drug-free state lasting 30 minutes to 4.5 hours into a dispensable drug-delivery state.
Administration of verapamil by displacement from the push composition.

Claim 7 is technically narrower than claim 1 because it expressly identifies hydroxypropylcellulose, cellulose acetate derivatives, and different PEO materials in the drug and push compositions. It is also a method claim, meaning infringement generally requires performance of the claimed administration method rather than merely making or selling a dosage form.

What do claims 8 through 11 cover?

Claims 8 through 11 add commercial-use characteristics:

Claim 8 covers an external coat that provides an instant dose.
Claim 9 requires delivery after a two-hour drug-free interval.
Claim 10 covers bedtime administration.
Claim 11 covers verapamil administration during night hours.

These claims are directed to chronotherapeutic use. The bedtime and nighttime limitations may create evidentiary issues because product labeling, physician instructions, and actual patient behavior do not always establish the same facts. Claim 8 is more commercially significant because an immediate-release overcoat is a common feature in delayed-release osmotic systems.

When did US Patent 5,160,744 expire?

US Patent 5,160,744 issued on November 3, 1992. It was subject to the pre-URAA patent-term framework, under which the ordinary term was 17 years from issuance. On that basis, the patent expired on November 3, 2009, absent a term adjustment or valid patent-term extension.

Event	Date or status
Patent issuance	November 3, 1992
Ordinary 17-year term	November 3, 2009
Current enforceability	Expired
Current blocking patent right	None from this patent

Patent-term restoration under 35 U.S.C. § 156 is generally associated with regulatory review of a specific drug product. The public commercial history of Covera-HS does not make the patent enforceable today. An expired patent cannot support a current Paragraph IV litigation strategy or an injunction against a new generic launch.

What was the Orange Book status of the patent?

US 5,160,744 was historically associated with the delayed-release verapamil product Covera-HS. Covera-HS was approved by the FDA as an extended-release verapamil hydrochloride product using a delayed and controlled osmotic delivery design.

The Orange Book significance was historical:

The patent identified the delivery technology associated with the reference product.
A generic applicant seeking approval before expiration could have faced a Paragraph IV certification issue.
After expiration, the patent ceased to provide a current Orange Book barrier to approval or launch.
The patent did not provide exclusivity for all verapamil products, including conventional immediate-release, sustained-release, or other extended-release formulations.

Orange Book listing does not establish that every verapamil product infringes the patent. It identifies patents submitted by the NDA holder as relevant to the approved product under the FDA listing framework. The scope of the issued claims remains controlling in an infringement analysis. [2][3]

What generic entry risks existed for Covera-HS?

Before expiration, generic entry risk depended on whether an applicant could:

Submit a Paragraph IV certification.
Avoid the structural limitations of the osmotic dosage form.
Demonstrate a different release mechanism.
Challenge validity, enforceability, or claim construction.
Wait for patent expiration and rely on an ordinary ANDA pathway.

The most practical design-around routes included:

Using a non-osmotic matrix system.
Eliminating the expanding push layer.
Using a different semipermeable membrane.
Moving PEO outside the claimed concentration range.
Using a non-verapamil active ingredient where relevant.
Providing delayed release through enteric coating rather than a swelling push composition.
Selecting a different delay mechanism or release profile.

Because claim 1 requires the elements to operate “in combination as a unit,” a product that achieves delayed delivery through an unrelated mechanism would have had a credible noninfringement position.

How strong was the patent estate for delayed-release verapamil?

The patent was technically strong against products closely copying the ALZA push-pull architecture. Its strongest features were the combination of:

A drug layer containing high PEO content.
A separate expanding push layer.
A slowly hydrating permeable wall.
A defined delayed-drug interval.
Optional immediate-release overcoat dosing.
Bedtime or nighttime administration.

Its weaknesses were the age of the patent, the breadth of certain functional language, the need to prove the delay interval, and the availability of non-osmotic formulation alternatives.

The patent also appears to be a platform patent rather than a complete modern patent estate. A commercial product may historically have been covered by additional formulation, manufacturing, labeling, or product-specific patents. Those rights must be analyzed separately from US 5,160,744. An expired platform patent does not establish freedom to operate where later patents remain active.

What formulation patents and manufacturing barriers were relevant?

The principal technical barriers were manufacturing and process control rather than the active ingredient itself.

Formulation barriers

Relevant formulation variables included:

PEO molecular weight and concentration.
Push-layer osmotic pressure.
Membrane permeability.
Hydroxypropylcellulose hydration rate.
Orifice size and formation method.
Drug-layer viscosity after hydration.
Coating thickness.
Immediate-release overcoat composition.
In vitro and in vivo delay reproducibility.

Manufacturing barriers

A manufacturer seeking to reproduce the platform would need to control:

Bilayer or multilayer tablet compression.
Membrane coating uniformity.
Passageway formation.
Drug-layer and push-layer adhesion.
Moisture exposure during processing.
Mechanical integrity during gastrointestinal transit.
Dissolution performance over the delayed interval.

These factors can create regulatory and commercial barriers even after patent expiration. They do not, however, extend the patent term.

Does the patent raise biosimilar risk?

No. Biosimilar law does not apply to verapamil, which is a small-molecule drug. The relevant FDA pathway is an abbreviated new drug application, or ANDA, rather than a 351(k) biosimilar application.

The competitive risk is therefore generic substitution risk, not biosimilar competition. A generic applicant would need to demonstrate pharmaceutical equivalence and bioequivalence to the applicable reference product and address any listed patents and exclusivity under the Hatch-Waxman framework. [4][5]

Which companies challenged or licensed the patent?

The patent record identifies the ALZA technology platform and its corporate successors as the principal rights holders or assignees associated with the invention. ALZA later became part of Johnson & Johnson.

A patent assignment is not the same as a commercial license. Public patent data alone does not establish the terms of any license involving ALZA, Johnson & Johnson, G.D. Searle, Pharmacia, or another Covera-HS commercial participant.

The patent’s expiration means that historical Paragraph IV activity is no longer commercially determinative. Current competition is governed primarily by FDA approval status, product-specific formulation patents, manufacturing capability, and market demand.

What is the current commercial exposure?

The patent itself creates no current royalty or infringement exposure because it is expired. Historical exposure was concentrated in products that copied the Covera-HS delayed-release architecture before November 2009.

Current commercial exposure may remain in three areas:

Later-issued patents covering specific formulations or manufacturing processes.
Regulatory requirements for generic extended-release verapamil.
Product liability and quality risks associated with delayed-release dose dumping or variable release.

The expired patent should therefore be treated as prior art and historical technology, not as a current exclusionary asset.

Key Takeaways

US Patent 5,160,744 covers an osmotic delayed-release dosage form for verapamil and related drug classes.
Claim 1 requires a verapamil drug layer, 20 wt% to 50% PEO, an expanding push layer, a slowly hydrating permeable wall, an exit means, and a delay of up to 4.5 hours.
Claim 7 is narrower and requires specific cellulose-based wall materials and different PEO materials in the drug and push compositions.
Claims 8 through 11 cover an immediate-release overcoat, two-hour delay, bedtime dosing, and nighttime administration.
The patent issued November 3, 1992, and expired under the ordinary term on November 3, 2009.
The patent was historically relevant to Covera-HS and the FDA Orange Book.
It does not create current generic, licensing, or biosimilar barriers.
Current freedom-to-operate analysis must examine later formulation, manufacturing, and product-specific patents.

FAQs

Is US Patent 5,160,744 still enforceable?

No. The patent expired on November 3, 2009 under its ordinary pre-URAA term.

Does US 5,160,744 cover all extended-release verapamil tablets?

No. It is limited to dosage forms containing the claimed osmotic architecture and delayed-delivery characteristics. Conventional matrix or non-osmotic extended-release products may fall outside its scope.

Can a generic verapamil manufacturer use the ALZA push-pull design today?

The expired patent cannot prevent use of the claimed design. The manufacturer must still assess later patents, FDA requirements, manufacturing controls, and other intellectual-property rights.

Is Covera-HS a biologic subject to biosimilar competition?

No. Covera-HS contains verapamil hydrochloride, a small-molecule active ingredient. Competition proceeds through the generic-drug framework, generally using an ANDA.

What is the most important design-around for this patent?

The clearest design-around strategy is to use a non-osmotic delayed-release mechanism or eliminate the separate expanding push composition, subject to analysis of the full claim set and any later patents.

References

United States Patent and Trademark Office. (1992). US Patent No. 5,160,744, delayed-delivery osmotic dosage form.
U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations: Orange Book.
U.S. Food and Drug Administration. (n.d.). Drugs@FDA: FDA-approved drugs, Covera-HS prescribing and approval information.
21 U.S.C. § 355. Abbreviated applications and patent certifications.
35 U.S.C. §§ 154, 156. Patent term and patent term extension.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	165000	⤷ Start Trial
Australia	2255092	⤷ Start Trial
Australia	654871	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 5,160,744

Summary for Patent: 5,160,744