US Patent 4,837,111: Doxazosin Osmotic Delivery Claims, Scope, Expiration, and Patent Landscape

US Patent 4,837,111 covers a highly specific osmotic drug-delivery device for administering doxazosin. The patent is directed to a cellulose acetate semipermeable wall, a compartment containing two polymer compositions, and a delivery passageway. Its principal commercial relevance was the extended-release doxazosin product Cardura XL.

The patent’s original 17-year term from issuance expired in 2006, absent an unusual term adjustment or extension. It therefore does not presently create an enforceable US patent barrier. The principal analytical issue is claim construction: several dependent claims supplied in the record specify ingredient quantities that fall outside the ranges recited in claim 1.

What does US Patent 4,837,111 cover?

US Patent 4,837,111 covers an elementary osmotic pump containing doxazosin and a separate osmotic driving composition. The patent was assigned to Alza Corporation, a major developer of osmotic oral delivery systems. The disclosed technology corresponds to the OROS-type platform used for controlled drug release.

The core claim requires all of the following elements:

Claim element	Required limitation
Drug	A therapeutically effective amount of doxazosin
Outer wall	At least partly cellulose acetate
Wall function	Permeable to exterior fluid
Internal structure	A compartment formed by the wall
First composition	Doxazosin, polyethylene oxide and hydroxypropylmethylcellulose
Second composition	Polyethylene oxide, sodium chloride and hydroxypropylmethylcellulose
Outlet	At least one passageway through the wall
Function	Delivery of doxazosin to the external environment

Claim 1 is a combination claim. A product must practice each required limitation to fall literally within its scope. A device using doxazosin in a conventional matrix tablet, capsule, multiparticulate system, or non-osmotic reservoir would not satisfy the claim unless it also included the claimed osmotic architecture.

What is the scope of independent claim 1?

Claim 1 has both structural and quantitative limitations.

Structural limitations

The claimed device must have:

A cellulose acetate wall, at least in part.
A compartment inside that wall.
Two compositions in the compartment.
At least one passageway connecting the compartment to the exterior.
A configuration capable of administering doxazosin.

The claim does not merely cover doxazosin in a controlled-release dosage form. It requires an osmotic device with a semipermeable wall and an outlet. The two-composition arrangement is also material. A single homogeneous drug layer may avoid literal infringement if the claim is construed to require distinct first and second compositions.

Quantitative limitations

As reproduced, claim 1 requires:

Component	Claimed amount
Doxazosin in first composition	1 to 25 mg
Polyethylene oxide in first composition	250 to 325 mg
Hydroxypropylmethylcellulose in first composition	10 to 30 mg
Polyethylene oxide in second composition	110 to 140 mg
Sodium chloride in second composition	40 to 70 mg
Hydroxypropylmethylcellulose in second composition	5 to 25 mg

These ranges materially narrow the claim. A competing device using the same OROS design but different polymer quantities could present a noninfringement position, subject to doctrine-of-equivalents risk.

The claim also raises a drafting issue. Several dependent claims list quantities that do not fall within the numerical ranges stated in claim 1. A dependent claim ordinarily incorporates every limitation of the claim from which it depends. The supplied text may therefore contain a transcription error, an amended claim history issue, or a claim-set inconsistency.

Are the dependent claims internally consistent?

Not on the face of the supplied claim text.

First-composition inconsistency

Claim 1 requires 250 to 325 mg of polyethylene oxide in the first composition. Claims 2 and 3 each specify:

83 mg of polyethylene oxide with a 100,000 molecular weight; and
56 mg of polyethylene oxide with a 200,000 molecular weight.

The combined polyethylene oxide amount is 139 mg, below claim 1’s stated minimum of 250 mg.

Claim 4 specifies 166 mg plus 111 mg of polyethylene oxide, for a total of 277 mg. That amount falls within claim 1’s range.

Second-composition inconsistency

Claim 1 requires 110 to 140 mg of polyethylene oxide in the second composition. Claim 5 specifies 64.5 mg, and claim 10 specifies the same 64.5 mg amount. Claim 6 specifies 129 mg, which falls within claim 1’s range.

The resulting comparison is:

Dependent claim	First-composition PEO	Second-composition PEO	Apparent relationship to claim 1
Claim 2	139 mg	Not stated	Outside first-composition range
Claim 3	139 mg	Not stated	Outside first-composition range
Claim 4	277 mg	Not stated	Within first-composition range
Claim 5	Not stated	64.5 mg	Outside second-composition range
Claim 6	Not stated	129 mg	Within second-composition range
Claim 7	Drug amount only	Not stated	Depends on claim 1
Claim 8	Drug amount only	Not stated	Depends on claim 1
Claim 9	Drug amount only	Not stated	Depends on claim 1
Claim 10	Not stated	64.5 mg	Outside second-composition range

If these quantities were present in the issued claims exactly as supplied, the dependent claims could create issues involving claim dependency, indefiniteness, written description, and prosecution-history interpretation. A definitive legal assessment requires the certified issued patent, prosecution history, certificates of correction, and any reexamination record.

What formulations are protected by US Patent 4,837,111?

The claims protect a particular osmotic formulation rather than every extended-release doxazosin formulation.

First composition

The first composition is the drug-containing layer. It includes doxazosin, polyethylene oxide and hydroxypropylmethylcellulose. The dependent claims identify specific doxazosin mesylate strengths:

Claim	Doxazosin mesylate amount
Claim 2	2.4 mg
Claim 3	4.8 mg
Claim 4	9.6 mg
Claim 7	Approximately 2.6 mg
Claim 8	Approximately 5.3 mg
Claim 9	Approximately 10.6 mg

The claims distinguish between doxazosin and doxazosin mesylate. A salt form may practice the claim where the claim and specification treat the salt as the administered form of doxazosin. The amount basis, whether measured as active moiety or salt, can affect infringement analysis.

Claims 2 through 4 also specify molecular-weight grades of polyethylene oxide and hydroxypropylmethylcellulose. Those limitations can narrow literal scope substantially. A formulation using polyethylene oxide of a different molecular weight, or a different suspending or swellable polymer, may avoid the dependent claims while still requiring analysis under the doctrine of equivalents.

Second composition

The second composition is the osmotic push layer. It contains:

High-molecular-weight polyethylene oxide;
Sodium chloride as an osmogen; and
Hydroxypropylmethylcellulose.

Claims 5 and 6 specify polyethylene oxide with molecular weights of 7,500,000. Claim 10 specifies polyethylene oxide with a molecular weight of 5,000,000. The molecular-weight limitation is important because high-molecular-weight polyethylene oxide controls swelling and displacement of the drug-containing layer.

A competing product could attempt to design around the patent with a different osmogen, different polymer, a single-layer system, a non-cellulose-acetate membrane, or a different delivery mechanism.

When did US Patent 4,837,111 lose exclusivity?

The patent appears to be a pre-1995 US patent governed by the former 17-year term from issuance under 35 U.S.C. § 154. The patent issued in 1989, placing ordinary expiration in 2006. Under that framework, expiration was determined from the issue date rather than the application filing date.

Event	Approximate date
US application filed	1987
Patent issued	1989
Ordinary 17-year patent expiration	2006
Current enforceable patent term	Expired, absent an unusual extension record

A patent-term extension under 35 U.S.C. § 156 is generally tied to regulatory review of an approved product and cannot be assumed from the existence of an FDA approval. The public patent-term record and FDA Orange Book must be checked for any specific extension or listed patent relationship. On the ordinary term calculation, US Patent 4,837,111 is no longer an enforceable patent.

What was the FDA and Orange Book relationship?

Doxazosin is an FDA-approved alpha-1 adrenergic antagonist used for hypertension and benign prostatic hyperplasia. Immediate-release doxazosin products were marketed under the Cardura brand. Extended-release doxazosin was marketed as Cardura XL.

The FDA approved Cardura XL as an extended-release tablet for hypertension and benign prostatic hyperplasia. The Orange Book distinguishes the reference listed drug, dosage form, strength, patents, and regulatory exclusivity. A patent covering an osmotic delivery system may be listed only if it meets the statutory listing requirements and claims the drug, formulation, or approved method of use.

The relevant regulatory distinction is:

Product category	Primary regulatory issue
Immediate-release doxazosin tablet	Active ingredient and conventional dosage-form competition
Extended-release doxazosin tablet	Formulation, delivery mechanism, and product-specific patent issues
Generic doxazosin mesylate	ANDA pathway for the relevant reference product
Biosimilar	Not applicable because doxazosin is a synthetic small molecule

FDA regulatory exclusivity and patent exclusivity are separate. The expiration of a patent does not itself establish that an ANDA is approvable, and an FDA exclusivity period does not extend patent duration.

Were Paragraph IV challenges relevant to this patent?

A Paragraph IV certification would have been relevant only if a generic applicant sought approval for a product referencing an FDA-listed drug with an unexpired patent listed in the Orange Book. Under the Hatch-Waxman framework, a generic applicant may certify that the listed patent is invalid, unenforceable, or will not be infringed. The first Paragraph IV filer can receive 180-day exclusivity in qualifying circumstances under 21 U.S.C. § 355(j)(5)(B)(iv).

Because the ordinary patent term of US Patent 4,837,111 ended in 2006, a current Paragraph IV challenge to this patent would have no practical role. Historical Paragraph IV activity would require review of FDA paragraph IV notices, ANDA litigation complaints, and Orange Book patent-listing records.

A Paragraph IV case involving another doxazosin formulation patent would not necessarily establish that US Patent 4,837,111 was litigated. Patent numbers and claim categories must be matched precisely.

What patent landscape surrounds doxazosin?

The doxazosin landscape has three distinct layers.

Active-ingredient patents

Doxazosin’s core compound and early pharmaceutical patents are old and no longer provide meaningful US exclusivity. Generic immediate-release doxazosin products entered after expiration of relevant compound and formulation rights.

Osmotic delivery patents

US Patent 4,837,111 belongs to the osmotic delivery category. Its technical scope is narrower than the broad OROS platform. It requires a doxazosin-specific formulation and defined material classes.

Other Alza patents may cover:

Semipermeable membrane systems;
Push-pull osmotic tablets;
Bilayer tablets;
Controlled-release dosage forms;
Passageway geometry;
Drug-layer and push-layer compositions; and
Manufacturing methods for osmotic devices.

A freedom-to-operate review must assess the entire Alza and successor patent family, not only US Patent 4,837,111.

Method-of-use and formulation patents

Method-of-use claims may address treatment of hypertension, benign prostatic hyperplasia, dosing intervals, or use of extended-release doxazosin. Formulation claims may cover specific release profiles, excipient ratios, coating structures, or tablet dimensions.

A product can avoid a device patent yet encounter a separate formulation or method-of-use patent. Conversely, a product may practice a broad release concept without practicing the specific polymer quantities in this patent.

How strong is the patent estate for this technology?

The patent estate is commercially weak today because US Patent 4,837,111 has expired. During its term, the patent had meaningful blocking potential because the claims combined:

A recognized osmotic platform;
A specific doxazosin drug layer;
A separate osmotic push layer;
Cellulose acetate;
Polyethylene oxide;
Sodium chloride; and
Defined composition ranges.

Its strength depended on claim construction and proof of formulation composition. A patent owner would have needed analytical evidence showing the accused product’s internal layers, polymer grades, quantities, wall material, and passageway structure.

The patent would have been less effective against:

Immediate-release doxazosin;
Non-osmotic extended-release products;
Multiparticulate or coated-pellet systems;
Matrix tablets;
Products using different polymer systems; and
Products with materially different layer ratios.

What generic entry risks exist?

For the expired patent itself, there is no current US patent-based entry risk. The commercial risks instead concern product substitution and regulatory qualification.

Generic scenario	Patent risk from US 4,837,111
Immediate-release doxazosin tablet	None from this patent
Non-osmotic extended-release formulation	Low literal-infringement risk
Bilayer osmotic doxazosin tablet	Historically meaningful; currently no enforceable risk from this patent
Product using claimed polymer amounts	No current risk from an expired patent
New product using a different active ingredient	No relevance
Biosimilar product	Not applicable

Manufacturing know-how may remain commercially important even after patent expiration. Critical process controls can include membrane coating, laser drilling or mechanical passageway formation, layer compression, moisture control, and release-profile testing. Those are operational barriers, not surviving patent exclusivity.

What litigation and settlement issues affect the patent?

No current enforceable litigation position can be inferred from the claim text alone. Historical litigation analysis would require docket review for:

Infringement complaints concerning Cardura XL;
ANDA applicants challenging listed patents;
Paragraph IV notices;
Declaratory-judgment actions;
Consent judgments;
License agreements;
Launch-at-risk disputes; and
Settlement agreements with generic manufacturers.

The existence of an FDA Orange Book listing would not establish infringement. Likewise, a settlement involving another Cardura XL patent would not necessarily cover US Patent 4,837,111.

How does this patent compare with other doxazosin rights?

Right type	Scope	Present commercial effect
Compound patent	Doxazosin molecule or salt	Expired
Immediate-release formulation patent	Tablet composition or dosage form	Generally expired or low residual significance
US 4,837,111	Doxazosin osmotic device with two compositions	Expired
Method-of-use patent	Treatment regimen or indication	Requires patent-specific status review
Manufacturing patent	Coating, drilling, compression, or process	Requires family-by-family review
FDA exclusivity	Regulatory approval protection	Product- and date-specific
Trade secret	Process parameters and manufacturing know-how	Can survive indefinitely if protected

Key Takeaways

US Patent 4,837,111 claims a two-composition osmotic doxazosin device, not doxazosin generally.
Claim 1 requires a cellulose acetate wall, internal compartment, drug layer, osmotic push layer, and passageway.
The claims include narrow quantities for polyethylene oxide, sodium chloride, hydroxypropylmethylcellulose, and doxazosin.
Claims 2, 3, 5, and 10 appear inconsistent with the numerical ranges in claim 1 as reproduced.
The patent’s ordinary pre-1995 term expired in 2006.
The patent creates no current US patent barrier to generic entry.
Doxazosin is a small molecule, so biosimilar analysis does not apply.
Current risk depends on other formulation, method-of-use, manufacturing, or regulatory rights, not this expired patent.

FAQs About US Patent 4,837,111

Does US Patent 4,837,111 cover Cardura?

It covers an osmotic extended-release doxazosin device associated with the technology used for Cardura XL. It does not cover all Cardura products or all doxazosin formulations.

Can a generic company sell doxazosin after this patent expired?

Expiration removes the patent-based barrier created by US Patent 4,837,111. A generic company must still satisfy FDA approval requirements and avoid any other unexpired patent or regulatory exclusivity.

Does changing polyethylene oxide molecular weight design around the patent?

It may avoid literal infringement of dependent claims that specify particular molecular-weight grades. The effect depends on the language of the issued claims, prosecution history, and potential doctrine-of-equivalents arguments.

Is doxazosin eligible for a biosimilar pathway?

No. Doxazosin is a synthetic small-molecule drug regulated through the conventional drug approval framework, including the ANDA pathway for qualifying generic products.

Are the quantities in the dependent claims legally significant?

Yes. Ingredient amounts and molecular-weight limitations can materially restrict claim scope. The apparent inconsistencies in the supplied claims require review of the official issued patent and prosecution record before relying on those claims for litigation or freedom-to-operate conclusions.

References

Alza Corporation. (1989). Osmotic device for delivering doxazosin (U.S. Patent No. 4,837,111). U.S. Patent and Trademark Office.
U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations. FDA.
U.S. Food and Drug Administration. (n.d.). Cardura XL prescribing information. FDA.
U.S. Code, 21 U.S.C. § 355. New drug applications and abbreviated applications.
U.S. Code, 35 U.S.C. § 154. Contents and term of patent; provisional rights.
U.S. Code, 35 U.S.C. § 156. Extension of patent term.
U.S. Code, 35 U.S.C. § 271(e). Infringement of patent.
U.S. Patent and Trademark Office. (n.d.). Patent term adjustment and patent term extension information. USPTO.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	96308	⤷ Start Trial
Canada	1315687	⤷ Start Trial
Germany	68910159	⤷ Start Trial
Denmark	135389	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 4,837,111

Summary for Patent: 4,837,111