US Patent 6,958,161: Claim Scope, Expiration, Doxycycline Formulation Coverage, and Patent Landscape

US Patent 6,958,161 protects a multiparticulate oral dosage form in which drug-containing cores are separated from a modified-release, particularly enteric or delayed-release, coating by an intermediate stabilizing coat. The central legal limitation is not merely the use of doxycycline or an enteric coating. The claimed product must preserve its dissolution behavior after storage within specified numerical limits compared with its pre-storage profile.

The patent is directed primarily to solid oral doxycycline products such as delayed-release tablets, capsules, and pellets. Its practical value was strongest against products using coated doxycycline particles or pellets with an intermediate stabilizing layer. The patent’s term has expired, eliminating current US infringement exposure under this patent alone.

What does US Patent 6,958,161 cover?

US 6,958,161, titled "Modified release preparations," claims pharmaceutical preparations containing coated drug cores. The patent issued on October 25, 2005. The claims focus on five technical elements:

A core containing an acid salt of a tetracycline-class antibiotic.
A modified-release coating around the core.
A stabilizing coat between the core and the modified-release coating.
A measurable post-storage dissolution profile.
A defined degree of similarity between pre-storage and post-storage dissolution.

The listed active ingredients are acid salts of:

Doxycycline
Tetracycline
Oxytetracycline
Minocycline
Chlortetracycline
Demeclocycline

The claims use "comprising," which generally leaves the formulation open to additional excipients, coatings, binders, fillers, lubricants, and other components unless those additions alter another express claim limitation.

What is the independent claim structure?

Claims 1, 14, 21, and 23 are the principal independent claims.

Claim	Claimed subject matter	Principal scope
1	Modified-release preparation	Broad product claim covering coated cores with a stabilizing coat and dissolution stability
14	Method of administration	Administration of the preparation to reduce nausea or gastric irritation associated with immediate-release dosing
21	Oral tablet	Doxycycline acid salt in coated cores with an intermediate stabilizing coat
23	Pellet	Doxycycline acid salt in a pellet intended for an oral dosage form

Claim 1 is the broadest composition claim because it covers multiple tetracycline active ingredients and multiple dosage forms. Claims 21 and 23 are narrower because they require an acid salt of doxycycline and specify a tablet or pellet context.

How does the dissolution-stability limitation affect infringement?

The principal functional limitation requires that, after storage, the amount of active ingredient released at any time remain within 40 percentage points of the amount released at the corresponding time before storage.

Claims 2 through 4 narrow this requirement:

Claim	Post-storage versus pre-storage dissolution requirement
1	Within 40 percentage points at any time
2	Within 30 percentage points at the majority of time points
3	Within 20 percentage points at the majority of time points
4	Within 10 percentage points at the majority of time points

This creates a claim hierarchy. Claim 1 is the broadest dissolution-stability claim. Claims 2 through 4 impose progressively tighter stability performance. A formulation that satisfies claim 4 will ordinarily satisfy the broader numerical requirement in claim 1, assuming all other elements are present.

The language creates several technical and litigation issues:

"At any time" applies broadly to the tested dissolution profile.
"Majority of time points" is not numerically defined in the claims.
The comparison must be made at corresponding time points.
The patent does not define a single universal storage condition in the claim text.
The result depends on the specified in vitro dissolution method, pH sequence, sampling schedule, and analytical method.

A generic or follow-on product could challenge infringement by showing that its post-storage profile falls outside the numerical range. It could also challenge validity by arguing that the functional result is inherent in prior-art coated pellets or that the claim lacks adequate written description or enablement for the full range of active ingredients and coating systems.

What formulations are protected by US 6,958,161?

The patent covers a wide range of modified-release coating systems, subject to the stabilizing-coat and dissolution-performance requirements.

Delayed-release and enteric coatings

Claims 5 through 10 cover:

Delayed-release coatings
Enteric coatings
Semi-enteric coatings
Pulsed-release coatings
Mixtures of enteric polymers
Enteric polymers combined with water-permeable, water-swellable, or water-soluble materials

Claim 6 requires a coating suitable to release:

20% or less of the active ingredient at pH about 1.2 by 20 minutes; and
At least 80% of the active ingredient at pH at least 5 by 60 minutes.

Claim 7 tightens those requirements to:

10% or less release at pH about 1.2 by 20 minutes; and
At least 90% release at pH at least 5 by 60 minutes.

Claim 10 identifies representative enteric materials:

Hydroxypropylmethyl cellulose phthalate
A pH-dependent anionic methacrylate polymer
Hydroxypropylmethyl cellulose acetate succinate

These limitations are consistent with multiparticulate doxycycline products designed to resist release in the stomach and release in the higher-pH intestinal environment.

Stabilizing coat

Claims 11 through 13 define the intermediate coat. It must be at least semipermeable in aqueous media and may contain water-soluble, water-swellable, or water-permeable polymeric or monomeric materials.

The listed materials include:

Hydroxypropylmethyl cellulose
Hydroxypropyl cellulose
Polyvinylpyrrolidone
Polyethylene glycol
pH-dependent anionic methacrylate polymers

The stabilizing coat distinguishes the claimed structure from a conventional formulation in which an enteric polymer is applied directly to a drug-containing core. Its stated function is to reduce interaction between the core and the outer modified-release layer during manufacture or storage.

Which dosage forms fall within the patent?

Capsules

Claim 15 covers a plurality of coated core elements placed in a capsule. This includes hard capsules containing pellets, beads, granules, or other multiparticulate units.

Tablets

Claim 16 covers coated core elements compressed into a tablet. Claims 17 through 19 specify that the coated core elements constitute:

20% to 40% by weight of the total tablet dosage weight;
25% to 35% by weight; or
About 30% by weight.

These limitations address a multiparticulate tablet rather than a conventional monolithic matrix tablet. The compression process must preserve the release properties of the coated cores.

Doxycycline delayed-release tablets

Claim 20 combines the principal commercial features:

A delayed-release coating;
An acid salt of doxycycline; and
Coated core elements compressed into a tablet.

Claim 21 separately claims an oral tablet containing doxycycline acid salt in coated cores with the stabilizing coat and dissolution-stability relationship. Claim 22 narrows claim 21 to a delayed-release coating.

Pellets

Claim 23 covers a doxycycline-containing pellet for use in an oral dosage form. The claim does not require that the pellet itself be sold as a capsule or tablet, allowing coverage at the intermediate dosage-form component level.

How broad is the method-of-use protection?

Claim 14 covers administering the claimed modified-release preparation to a patient when the active ingredient, in immediate-release form, normally causes nausea and gastric irritation. Claim 24 narrows that method to delayed-release doxycycline.

The method claims are narrower than they may first appear because infringement requires:

A qualifying active ingredient;
A modified-release preparation meeting the product limitations;
The claimed administration;
A drug that normally causes nausea and gastric irritation in immediate-release form.

The product claims are more commercially important because they can be asserted against manufacture, sale, or importation of the dosage form without proving a particular patient’s treatment or a specific clinical outcome.

When did US Patent 6,958,161 expire?

The patent’s US term expired based on the 20-year term measured from its relevant nonprovisional filing or priority framework. Public patent records place the operative term in the 2021 period. The patent is therefore expired and cannot support a new US infringement action for activities occurring after expiration.

Event	Date
US patent issued	October 25, 2005
Patent term basis	20-year term from applicable US filing framework
Effective expiration period	2021
Current enforceability	Expired

Any patent-term adjustment or terminal-disclaimer information should be taken from the USPTO patent record for a transaction-grade opinion. Expiration does not remove the patent from historical patent landscapes, litigation analyses, or freedom-to-operate records, but it eliminates ordinary prospective enforcement based on the patent.

What is the Orange Book status of US 6,958,161?

US 6,958,161 was associated with the patent landscape for delayed-release doxycycline products, including Doryx-related products and other oral doxycycline formulations. Orange Book relevance depends on whether the patent was submitted for a particular approved drug product and listed by FDA for that product’s NDA and dosage form.

An Orange Book-listed formulation patent can create an ANDA certification issue even when it does not claim the active ingredient itself. A generic applicant may need to address the patent through:

Paragraph I certification, if the patent information has expired or is not applicable;
Paragraph III certification, if the applicant accepts delayed approval until expiration;
Paragraph IV certification, if the applicant asserts invalidity, unenforceability, or noninfringement; or
A section viii statement, if the patent claims an indication or method of use that the ANDA applicant will omit.

Because 6,958,161 has expired, it is no longer a prospective Orange Book blocking patent. Historical Paragraph IV filings and litigation remain relevant for understanding generic-entry strategy, but they do not create a current regulatory stay under this patent.

Which companies challenged doxycycline formulation patents?

The delayed-release doxycycline market produced Paragraph IV disputes involving branded doxycycline manufacturers and generic applicants. The relevant disputes generally concerned:

Multiparticulate doxycycline formulations;
Enteric or delayed-release coatings;
Stabilizing layers;
Tablet compression of coated pellets;
Dissolution characteristics; and
Later-generation Doryx and Oracea formulations.

The commercially important branded companies included Warner Chilcott and related entities, while generic challenges involved companies such as Mylan, Actavis, and other ANDA sponsors depending on the specific doxycycline product and patent family.

A Paragraph IV challenge to a related patent did not necessarily establish invalidity or noninfringement of US 6,958,161. Each patent required separate analysis of claim construction, formulation testing, prosecution history, and prior-art disclosures.

What patent litigation affected this patent family?

The patent belongs to the broader litigation environment surrounding delayed-release doxycycline products. Litigation issues in this field typically included:

Whether an ANDA product contained an intermediate stabilizing coat;
Whether the product satisfied the patent’s dissolution-profile limitations;
Whether coated particles remained identifiable after tablet compression;
Whether the claimed stability result was inherent in prior art;
Whether the claims were enabled across the full range of tetracycline salts and coating materials; and
Whether later patents were patentably distinct from the earlier coated-core technology.

The central litigation risk was product-specific. A generic applicant could avoid literal infringement by using a different coating architecture, a different stabilization mechanism, or dissolution behavior outside the claimed profile. The patentee could respond with doctrine-of-equivalents arguments, although the numerical dissolution limitations would make prosecution-history and claim-scope constraints important.

How strong was the patent estate?

Strengths

The patent had several commercially useful features:

It claimed a product architecture rather than only a manufacturing process.
It covered doxycycline and several related tetracycline salts.
It captured tablets, capsules, and pellets.
It included both broad and narrower dissolution-stability thresholds.
It covered common enteric and polymeric excipients.
It linked the intermediate coat to long-term dissolution performance.

Weaknesses

The main vulnerabilities were:

Functional dissolution limitations can be difficult to prove consistently.
"Majority of time points" lacks a precise claim definition.
The claims span numerous active ingredients and polymer combinations.
Prior art on enteric-coated pellets and stabilizing subcoats could support obviousness arguments.
A generic product could design around the intermediate layer or use a different release-control mechanism.
The patent’s remaining commercial value declined sharply as expiration approached.

The patent was stronger as a targeted formulation patent than as a broad doxycycline monopoly. It did not cover all doxycycline products, all delayed-release dosage forms, or doxycycline as an active pharmaceutical ingredient.

How does US 6,958,161 compare with other doxycycline patents?

Patent category	Typical protected subject matter	Relationship to US 6,958,161
Active-ingredient or salt patents	Doxycycline compound, salt, or chemical form	6,958,161 is narrower and formulation-focused
Immediate-release formulations	Conventional doxycycline tablets or capsules	Usually outside the core claim architecture
Delayed-release formulations	Enteric or controlled-release doxycycline dosage forms	Closest competing patent category
Multiparticulate patents	Pellets, beads, coated cores, capsule or tablet delivery	Directly overlaps the technical field
Method-of-use patents	Acne, rosacea, periodontal disease, inflammation	6,958,161 has limited method-of-use coverage
Manufacturing patents	Coating, layering, drying, compression, or pellet processes	Potentially complementary or design-around territory
Biologic patents	Monoclonal antibodies and biosimilar products	Not relevant to this small-molecule patent

The most important comparison is with later doxycycline formulation patents. A later patent may remain relevant even though 6,958,161 has expired if it claims a distinct coating composition, particle-size distribution, dose regimen, manufacturing process, or specific commercial product.

Are biosimilar risks relevant?

No. Doxycycline is a small-molecule drug regulated through the abbreviated new drug application pathway, not the biosimilar pathway under section 351(k) of the Public Health Service Act.

Competitive entry occurs through generic doxycycline products, including ANDAs for:

Immediate-release tablets and capsules;
Delayed-release tablets;
Delayed-release capsules;
Pellets or multiparticulate products; and
Product-specific formulations referencing approved doxycycline products.

What generic launch scenarios existed?

Before expiration, a generic sponsor facing this patent had four principal strategies:

File a Paragraph IV certification and challenge validity, enforceability, or infringement.
Develop a formulation that did not use an intermediate stabilizing coat.
Use a modified-release system that failed the claimed dissolution-stability relationship.
Wait for patent expiration and launch under a non-Paragraph-IV pathway.

After expiration, the patent no longer prevents launch. Remaining barriers may arise from other unexpired patents, FDA product-specific requirements, manufacturing complexity, or commercial scale-up.

The patent’s technical barriers were most significant for a generic seeking to replicate a branded multiparticulate doxycycline tablet. A simple immediate-release doxycycline product would generally not practice the core coated-core limitations.

What manufacturing and IP barriers remain?

The expired patent does not eliminate technical barriers. A commercial delayed-release doxycycline product may still require:

Uniform drug loading in pellets or cores;
Consistent application of the stabilizing coat;
Controlled enteric-polymer weight gain;
Resistance to gastric pH;
Rapid release at intestinal pH;
Stability through tablet compression;
Protection from moisture and heat;
Dose uniformity across multiparticulate units; and
Reproducible dissolution after storage.

Potentially live patent rights may still cover coating equipment, polymer combinations, particle-size distributions, manufacturing sequences, release profiles, or specific branded products. A current freedom-to-operate review must therefore examine the complete patent family and later continuation, divisional, and improvement patents, not 6,958,161 in isolation.

What was the commercial significance of the patent?

The patent supported differentiated doxycycline products intended to improve gastrointestinal tolerability and control release. Its commercial relevance was tied to delayed-release products sold for acne, rosacea, periodontal disease, and related inflammatory or infectious indications.

The patent did not protect doxycycline revenue generally. Exposure was limited to products using the claimed formulation architecture. Revenue risk increased where a branded product depended on coated pellets or delayed-release tablets and where generic applicants could replicate the dosage form through an ANDA.

Key Takeaways

US 6,958,161 claims coated drug cores with an intermediate stabilizing coat and a modified-release outer coating.
The central limitation is preservation of the dissolution profile after storage.
Claims 1 through 4 create progressively tighter dissolution-stability thresholds.
Claims 20 through 24 focus on delayed-release doxycycline tablets, pellets, and administration methods.
The patent covers formulation architecture, not doxycycline generally.
It is relevant to historical Doryx and delayed-release doxycycline patent disputes.
The patent expired in the 2021 period and is no longer a current US blocking right.
No biosimilar pathway applies because doxycycline is a small-molecule drug.
Current generic risk depends on other unexpired formulation, manufacturing, method-of-use, and product-specific patents.

FAQs About US Patent 6,958,161

Does US 6,958,161 cover ordinary doxycycline tablets?

No. The principal claims require coated core elements, a modified-release coating, and an intermediate stabilizing coat. A conventional immediate-release doxycycline tablet would generally fall outside the core product claims.

Does the patent cover doxycycline hyclate?

The claims cover acid salts of doxycycline. Doxycycline hyclate is an acid-addition salt and was within the technical category targeted by the doxycycline claims, subject to satisfaction of the coating and dissolution limitations.

Can a formulation infringe without using the exact polymers listed in the patent?

Yes. The claims are not limited in every instance to the named polymers. Several claims use broader functional or categorical language covering water-permeable, water-soluble, or water-swellable materials and modified-release coating systems.

Did expiration of US 6,958,161 invalidate related doxycycline patents?

No. Patent expiration is specific to the individual patent. Related patents covering different formulations, manufacturing methods, products, or indications must be analyzed separately.

Is US 6,958,161 relevant to an ANDA filed today?

It may remain relevant as prior art and as a historical patent-family reference, but its expired term does not independently block a current ANDA launch. Current regulatory risk depends on other listed and unexpired patents associated with the referenced doxycycline product.

References

United States Patent and Trademark Office. (2005). U.S. Patent No. 6,958,161, Modified release preparations.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book.
U.S. Food and Drug Administration. (n.d.). Abbreviated new drug application (ANDA) process.
United States Code, 35 U.S.C. § 154. Patent term.
United States Code, 21 U.S.C. § 355. New drug applications and abbreviated applications.

Details for Patent: 6,958,161

Summary for Patent: 6,958,161