US Patent 7,250,176: Claim Scope, Expiration, Orange Book Status, and Generic Entry Risk

US Patent 7,250,176 protected an extended-release amoxicillin/potassium clavulanate composition associated with Augmentin XR. Its core technology was a two-phase solid dosage form that released amoxicillin in an initial phase and a delayed or retarded phase. The claims covered formulation architecture, sodium amoxicillin-organic acid interactions, bilayer tablets, dissolution performance, pharmacokinetic parameters, and treatment of respiratory bacterial infections.

The patent’s enforceable term has ended. It no longer creates a current US patent barrier to generic development, although its claim structure remains relevant for freedom-to-operate analysis, validity review, and historical Orange Book litigation.

What technology did US Patent 7,250,176 protect?

The patent protected a method of treating bacterial infection by administering a solid composition containing:

Amoxicillin;
Potassium clavulanate;
A first release phase containing clavulanate and a first amoxicillin portion; and
A second release phase containing a soluble amoxicillin salt, an organic acid, and, in many claims, a release-retarding excipient.

The claimed formulation was designed to provide rapid initial antibiotic exposure followed by sustained amoxicillin exposure. The patent focused on maintaining amoxicillin concentrations above a microbiological threshold while administering the product approximately every 12 hours.

The principal formulation concept was a 2,000 mg amoxicillin dose containing approximately 125 mg of potassium clavulanate, corresponding to an amoxicillin-to-clavulanate ratio near 16:1 by weight. The product architecture was consistent with the extended-release Augmentin XR dosage form described in FDA labeling.

Core claim elements

Claim element	Scope
Active ingredients	Amoxicillin and potassium clavulanate
Dosage form	Solid dosage form, including compressed and bilayer tablets
Release architecture	First release phase plus second release phase
First phase	Potassium clavulanate and first amoxicillin portion
Second phase	Soluble amoxicillin salt, organic acid, and optionally release-retarding polymer
Preferred salt	Sodium amoxicillin or crystallized sodium amoxicillin
Preferred acid	Citric acid, particularly anhydrous citric acid
Preferred polymer	Xanthan gum
Amoxicillin dose	Approximately 700 mg to 2,600 mg, with specific claims to 1,000 mg and 2,000 mg
Dose interval	Approximately 12 hours
Preferred ratio	First-phase to second-phase amoxicillin ratio of about 9:7
Release testing	USP Apparatus 2, 75 rpm, 900 mL deionized water
Clinical performance	Cmax of at least 12 or 16 micrograms/mL and time above 4 micrograms/mL for at least 4.4 hours

How broad is claim 1 of US Patent 7,250,176?

Claim 1 is a method-of-treatment claim with a substantial formulation limitation. It is broader than the later claims because it does not require a specific acid, tablet configuration, dosage amount, release polymer, dissolution profile, or pharmacokinetic result.

To fall within claim 1, an accused product and use would generally need to satisfy all of the following limitations:

Treatment of a bacterial infection in a patient.
Administration of a therapeutically effective amount.
A solid composition containing amoxicillin and potassium clavulanate.
A first release phase containing potassium clavulanate and a first amoxicillin portion.
A second release phase containing a soluble amoxicillin salt and an organic acid.
Intimate admixture of the soluble amoxicillin salt and organic acid.
A soluble-amoxicillin-to-organic-acid ratio from 20:1 to 1:2.

The claim does not expressly require:

A bilayer tablet;
A 2,000 mg dose;
A 12-hour administration interval;
Xanthan gum;
A specified dissolution profile;
A stated Cmax or T>MIC value;
Citric acid; or
Sodium amoxicillin.

Those limitations appear in dependent claims and claim 138.

Claim construction issues

Several terms would have been central in an infringement dispute:

"First release phase" and "second release phase": The claims require two functionally distinct release phases, but do not necessarily require two physically separate layers in the broadest claims.
"Intimate contact": This limitation focuses on direct or close admixture of the soluble amoxicillin salt and organic acid. A formulation using spatial separation, coating, encapsulation, or a different pH-control mechanism could avoid literal infringement.
"Soluble salt of amoxicillin": Sodium amoxicillin is the clearest example, but the broad claim language may encompass other pharmaceutically acceptable soluble salts.
"Release rate ... reduced": Claim 104 and related claims add a comparative functional limitation requiring slower release from the second phase than from the first phase.
"Composition in solid form": Liquid suspensions and conventional immediate-release tablets would generally fall outside the claimed dosage-form architecture.

What do claims 138 through 146 add?

Claim 138 is the most commercially focused independent claim. It combines the principal formulation and clinical-performance limitations into one claim.

A product-use combination within claim 138 would require:

Approximately 2,000 mg of amoxicillin;
Potassium clavulanate;
Two release phases;
A listed organic acid;
A 2:1 to 20:1 amoxicillin-to-clavulanate ratio;
Administration approximately every 12 hours;
A release-retarding excipient;
Specific five-point dissolution ranges;
Cmax of at least 12 micrograms/mL; and
Plasma amoxicillin concentration above 4 micrograms/mL for at least 4.4 hours.

Claims 139 through 146 narrow the indication to respiratory tract infections, including:

Community-acquired pneumonia;
Acute exacerbation of chronic bronchitis; and
Acute bacterial sinusitis.

The claims also identify Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis, including drug-resistant and penicillin-resistant S. pneumoniae.

From an enforcement perspective, claim 138 is narrower but more closely aligned with the commercial product. It would have presented greater proof burdens because infringement could require pharmacokinetic and dissolution testing, not merely product composition analysis.

What formulations are protected by US Patent 7,250,176?

The strongest formulation-specific protection is concentrated in the following combination:

Feature	Preferred claimed embodiment
Tablet	Compressed bilayer or monolith tablet
First phase	Amoxicillin trihydrate or soluble amoxicillin plus all potassium clavulanate
Second phase	Crystallized sodium amoxicillin plus anhydrous citric acid
Phase ratio	First-phase to second-phase amoxicillin near 9:7
Acid ratio	Sodium amoxicillin to citric acid approximately 1:1
Total amoxicillin	About 1,000 mg or 2,000 mg
Amoxicillin-to-clavulanate ratio	Approximately 14:1 to 16:1
Retarding excipient	Xanthan gum, including pharmaceutical-grade 200 mesh
Release profile	45% to 65% at 30 minutes and 70% to 100% at 240 minutes

Claims 75 through 89 cover compressed and multilayer tablets. Claims 90 through 103 cover release-retarding polymers, particularly xanthan gum. Claims 107 through 112 cover dissolution windows. Claims 113 through 127 cover pharmacokinetic and pharmacodynamic results.

These claim groups create a layered estate. A generic could avoid one layer while potentially implicating another. For example, a formulation might avoid xanthan gum but still satisfy the broad two-phase and organic-acid limitations.

How does the patent distinguish the first and second release phases?

The first phase is principally the rapid-release component. It contains potassium clavulanate and part of the amoxicillin. The second phase contains the remaining amoxicillin as a soluble salt in intimate contact with an organic acid.

The patent describes the organic acid as modifying the release behavior of soluble amoxicillin. The second phase may also contain a swelling or gelling polymer, such as xanthan gum, to further retard release.

The claim set covers both:

Physically separated phases, such as separate layers or dosage units; and
Functionally distinct phases where the release behavior differs, even if the product architecture is not expressly limited to a particular tablet geometry.

What patent landscape surrounded Augmentin XR?

The relevant landscape consisted primarily of GSK or SmithKline Beecham patents covering extended-release amoxicillin/clavulanate formulations and associated manufacturing or use concepts.

Patent or regulatory asset	General subject matter	Commercial relevance
US 7,250,176	Two-phase amoxicillin/potassium clavulanate solid dosage forms and treatment methods	Core extended-release formulation patent
Related earlier GSK family patents	Amoxicillin/clavulanate compositions and extended-release technology	Potentially overlapping formulation protection
Augmentin XR NDA 050725	Extended-release amoxicillin/clavulanate tablets	Regulatory basis for the commercial product
Conventional Augmentin products	Immediate-release amoxicillin/clavulanate tablets and suspensions	Different formulation and dosing technology

The principal competitive distinction was between conventional immediate-release Augmentin and Augmentin XR. Immediate-release products generally used more frequent dosing and did not require the two-phase dissolution and pharmacokinetic profile claimed by the patent.

Augmentin versus Augmentin XR

Attribute	Conventional Augmentin	Augmentin XR
Release profile	Immediate release	Extended or biphasic release
Typical dosing concept	More frequent administration	Approximately every 12 hours
Core patent issue	Conventional composition and uses	Two-phase release architecture
2,000 mg dose	Not generally the same XR configuration	Central commercial embodiment
Organic-acid controlled release	Not required	Central claimed mechanism
Bilayer formulation	Not required	Covered by dependent claims
Generic pathway	Conventional ANDA competition	Formulation-specific ANDA or alternative design

When did US Patent 7,250,176 lose exclusivity?

US Patent 7,250,176 is no longer enforceable because its patent term ended in the early 2020s. The patent was issued on August 7, 2007, but the relevant expiration date is determined by the effective US filing and priority history, adjusted for any applicable patent-term adjustment, not by the issue date alone.[1]

The patent’s commercial exclusivity also depended on FDA regulatory exclusivity and the continued marketing status of Augmentin XR. FDA approval of a product does not extend a patent after the patent term ends. A patent-term extension under 35 U.S.C. § 156 would have been separately identified in USPTO and FDA records; US Patent 7,250,176 is generally treated as an expired patent in current US competitive analyses.

Exclusivity timeline

Event	Timing
Priority and international development	Before US issuance
US patent grant	August 7, 2007
Augmentin XR regulatory approval	FDA-approved extended-release product
Patent term end	Early 2020s
Current patent barrier	None from US 7,250,176
Current biosimilar relevance	None

What was the Orange Book status of US Patent 7,250,176?

The patent was associated with the extended-release amoxicillin/clavulanate product Augmentin XR rather than with every conventional Augmentin presentation. Orange Book listing status is product- and NDA-specific. A patent listed for Augmentin XR would not automatically cover an immediate-release amoxicillin/clavulanate tablet or suspension.

The Orange Book framework distinguishes among:

Drug substance patents;
Drug product patents;
Method-of-use patents.

US 7,250,176 was principally a drug-product and method-of-use patent. Its claims were tied to the composition and administration of a particular extended-release dosage form.

Once the patent expired, an ANDA applicant no longer needed to make a Paragraph IV certification against that patent. A Paragraph III certification would have been relevant before expiry if the applicant accepted delayed approval until the patent’s expiration date. After expiration, the patent no longer supports a 30-month stay or a statutory basis for blocking ANDA approval.

Which companies challenged the patent?

The supplied claim text does not identify a specific Paragraph IV challenger, litigation docket, settlement, or license. A definitive company-by-company litigation history cannot be established from the claims alone.

The likely regulatory challengers would have been manufacturers pursuing an ANDA for an extended-release amoxicillin/clavulanate product. Such an applicant would have had to address:

Pharmaceutical equivalence;
Bioequivalence;
The two-phase release profile;
Amoxicillin and clavulanate exposure;
Dissolution similarity;
The listed patent through a Paragraph IV certification or other Orange Book certification.

No biosimilar pathway applies because amoxicillin and clavulanate are small-molecule active ingredients. Competition would proceed through the ANDA pathway, not through a biosimilar application under the Biologics Price Competition and Innovation Act.

What generic entry risks did the patent create?

Before expiration, generic entry risk depended on whether the proposed product used the same release mechanism. The main infringement exposure points were:

A bilayer tablet with a clavulanate-containing first layer.
A second layer containing sodium amoxicillin and citric acid.
An amoxicillin-to-clavulanate ratio near 14:1 to 16:1.
A 9:7 distribution of amoxicillin between release phases.
Xanthan gum in the second phase.
The specified dissolution ranges.
A 2,000 mg dose administered every 12 hours.
Pharmacokinetic performance meeting the claimed Cmax and T>MIC thresholds.

Design-around options

A manufacturer could have reduced literal infringement risk by using:

An immediate-release rather than extended-release product;
A single-phase formulation;
A delayed-release coating rather than intimate organic-acid admixture;
A different amoxicillin salt;
A different pH-modifying agent;
A different phase ratio;
A non-bilayer multiparticulate system;
A release-retarding polymer other than xanthan gum;
A different amoxicillin-to-clavulanate ratio; or
A dosing regimen not based on the claimed 12-hour extended-release profile.

These alternatives would require separate analysis under the doctrine of equivalents. A design that changes only the excipient while preserving the same phase structure and release mechanism could remain exposed to an equivalents theory.

How strong was the patent estate?

The patent was technically specific but commercially meaningful. Its strength varied by claim category.

Claim category	Relative strength before expiry	Principal vulnerability
Broad two-phase method claim	Moderate	Construction of release phases and intimate contact
Sodium amoxicillin plus organic acid	Moderate to strong	Prior-art formulation disclosures
Bilayer tablet claims	Moderate	Alternative multiparticulate or coated systems
Xanthan gum claims	Narrow but concrete	Easy excipient substitution
Dissolution claims	Moderate	Reproducibility and testing variability
Pharmacokinetic claims	Narrow	Experimental proof and inherent-result disputes
Claim 138	Strong commercial fit, narrow scope	Multiple cumulative limitations

The patent’s principal enforcement advantage was the number of dependent claims. Even if a challenger defeated broad claims, narrower claims could preserve protection for the commercial formulation. Its principal weakness was that many claims depended on measurable functional results, creating potential validity and infringement disputes over test conditions, patient population, and formulation variability.

Did licensing or settlement agreements affect the patent?

The supplied material does not identify a license, settlement, authorized generic arrangement, or covenant not to sue. No such transaction should be attributed to US Patent 7,250,176 without a specific agreement, court docket, SEC filing, or FDA record.

Because the patent has expired, any historical settlement would have limited current commercial significance except for launch timing, damages exposure, or antitrust analysis.

What is the current commercial impact?

The direct patent impact is zero because the patent term has ended. Current competition is controlled by:

FDA approval requirements;
Product discontinuation or availability;
Bioequivalence to the relevant extended-release reference product;
Manufacturing complexity;
Stability of amoxicillin and clavulanate;
Commercial demand for twice-daily high-dose therapy; and
Any remaining patents in related formulation or manufacturing families.

There is no biosimilar barrier. A current entrant would pursue an ANDA or another applicable small-molecule pathway, not a biosimilar application.

Key Takeaways

US Patent 7,250,176 covered extended-release amoxicillin/potassium clavulanate treatment methods.
The central invention was a two-phase solid dosage form with rapid and retarded amoxicillin release.
The preferred embodiment used a 2,000 mg amoxicillin dose, potassium clavulanate, sodium amoxicillin, anhydrous citric acid, and a release-retarding polymer such as xanthan gum.
Claims covered bilayer tablets, phase ratios, dissolution profiles, pharmacokinetics, and respiratory infections.
The patent was commercially associated with Augmentin XR.
The patent term ended in the early 2020s, eliminating a current US patent block.
No biosimilar pathway applies because the active ingredients are small molecules.
Historical Paragraph IV risk would have focused on two-phase release architecture, organic-acid admixture, dissolution behavior, and pharmacokinetic performance.
A current generic entrant faces formulation, bioequivalence, manufacturing, and regulatory issues rather than an enforceable barrier from US 7,250,176.

FAQs

What drug was protected by US Patent 7,250,176?

The patent protected an extended-release amoxicillin and potassium clavulanate formulation associated with Augmentin XR.

Does US Patent 7,250,176 cover regular Augmentin tablets?

Not necessarily. The claims require a two-phase release composition with specified formulation features. Conventional immediate-release Augmentin products generally do not meet those limitations.

Is Augmentin XR a biologic requiring a biosimilar application?

No. Amoxicillin and clavulanate are small-molecule active ingredients. A competing product would generally use the ANDA pathway.

Could a generic use citric acid and avoid the patent?

Not if the product otherwise satisfies an applicable citric-acid claim and the required two-phase, salt, ratio, and release limitations. Using citric acid alone does not determine infringement.

Does patent expiration eliminate FDA bioequivalence requirements?

No. Patent expiration removes the patent barrier but does not eliminate FDA requirements for pharmaceutical equivalence, bioequivalence, quality, stability, labeling, and manufacturing controls.

References

United States Patent and Trademark Office. (2007). U.S. Patent No. 7,250,176, Pharmaceutical compositions comprising amoxicillin and clavulanic acid.
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.). Augmentin XR prescribing information.
35 U.S.C. §§ 154, 156, 271, 355.
U.S. Pharmacopeial Convention. (1995). United States Pharmacopeia 23, General Chapter <711>, Dissolution.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
African Regional IP Organization (ARIPO)	1806	⤷ Start Trial
Argentina	031068	⤷ Start Trial
Austria	242629	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 7,250,176

Summary for Patent: 7,250,176