U.S. Patent 7,361,676: Febuxostat Crystal A Tablet Claims, Expiration, and Patent Landscape

U.S. Patent 7,361,676 protects a narrow febuxostat tablet formulation using a defined crystalline form, a specified particle-size range, and conventional excipients. Its core protection is not the febuxostat molecule itself. The patent is directed to tablets containing "crystal A" of febuxostat, identified by a specific X-ray powder diffraction pattern and an average particle diameter of 12.9 to 26.2 micrometers.

The patent’s nominal U.S. term ended in November 2022, subject to any applicable patent-term adjustment. It therefore does not present a current U.S. blocking patent for ordinary generic febuxostat entry. Its historical importance was greater because it covered the commercial tablet technology associated with Takeda’s Uloric product.

What drug and technology does U.S. Patent 7,361,676 cover?

The active pharmaceutical ingredient is febuxostat, chemically identified in the patent as 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazolecarboxylic acid. Febuxostat is a non-purine selective xanthine oxidase inhibitor used to reduce serum uric acid in patients with gout and hyperuricemia.

The patent covers a solid oral tablet containing:

Element	Requirement
Active ingredient	Crystal A of febuxostat
Crystal identity	XRPD peaks at 2θ values of 6.62°, 7.18°, 12.80°, 13.26°, 16.48°, 19.58°, 21.92°, 22.68°, 25.84°, 26.70°, 29.16°, and 36.70°
Particle size	Average particle diameter of 12.9 to 26.2 μm
Formulation components	At least one excipient and a disintegrating agent
Manufacturing option	Wet granulation
Named excipients	Lactose and partly pregelatinized starch
Binder option	Hydroxypropyl cellulose
Coating option	Polyethylene glycol

The claims combine a polymorph limitation with a particle-engineering limitation. A tablet containing chemically identical febuxostat in a different crystal form is outside the literal scope of the independent product claim. A tablet using crystal A but having an average particle diameter below 12.9 μm or above 26.2 μm also falls outside the express particle-size limitation.

What does claim 1 of U.S. Patent 7,361,676 protect?

Claim 1 is the principal product claim. It requires all of the following:

A tablet.
Crystal A of febuxostat.
The claimed XRPD diffraction pattern.
An average crystal-A particle diameter between 12.9 and 26.2 μm.
An excipient.
A disintegrating agent.

The claim does not require wet granulation, lactose, partly pregelatinized starch, hydroxypropyl cellulose, or polyethylene glycol. Those features appear in dependent claims 2 through 5.

The claim therefore reaches a broad range of tablet compositions, but only within a narrow solid-state and particle-size window. The excipient and disintegrant limitations prevent the claim from covering bulk febuxostat crystal A, capsules, suspensions, or other dosage forms lacking the required tablet structure.

How does the XRPD limitation narrow infringement?

The XRPD limitation is a product identity limitation. A product generally may infringe even if the manufacturer uses a different process, provided the resulting tablet contains the claimed crystal form.

The listed diffraction peaks are central to claim scope. In practice, infringement analysis would require:

Sampling the active ingredient or tablet;
Performing XRPD testing under controlled conditions;
Comparing peak positions and intensities with the claimed pattern;
Determining whether the tested material is crystal A;
Measuring the average particle diameter using the applicable analytical method.

The claims state the peak positions but do not reproduce, in the supplied text, numerical tolerance ranges, relative intensities, sample-preparation conditions, or a particle-size measurement technique. Those details would be important in a litigation record because XRPD peak position and particle-size results can vary with instrumentation, sample preparation, aggregation, milling, and analytical methodology.

What do claims 2 through 5 add?

Claims 2 through 5 narrow the product claim through manufacturing and formulation features.

Claim	Added limitation	Commercial significance
2	Tablet prepared by wet granulation	Captures a common industrial process for improving blend uniformity and tabletability
3	Lactose and/or partly pregelatinized starch as excipient	Targets specified diluent and dry-binding systems
4	Hydroxypropyl cellulose as binder	Covers a named binder option
5	Polyethylene glycol coating	Covers a particular film-coating component

Claim 3 is drafted as an alternative-group limitation. It requires one or more excipients selected from lactose and partly pregelatinized starch. A formulation using only microcrystalline cellulose, mannitol, or another non-listed excipient would not literally satisfy that limitation.

Claim 4 is narrower because hydroxypropyl cellulose must be present as a binder. Its presence for another function could create a claim-construction issue, but a generic manufacturer using hydroxypropyl cellulose in the granulation liquid would face a stronger infringement argument.

Claim 5 requires polyethylene glycol coating. A coating made exclusively with hydroxypropyl methylcellulose, polyvinyl alcohol, or another polymer would generally avoid literal infringement of claim 5, although it could remain within claim 1 or another applicable claim.

What do claims 6 through 10 protect?

Claims 6 through 10 are process claims directed to producing the claimed tablet.

Claim 6 requires combining:

Crystal A of febuxostat;
The claimed XRPD pattern;
The 12.9 to 26.2 μm average particle-size range;
An excipient; and
A disintegrating agent.

Claims 7 through 10 add the same process and formulation limitations found in claims 2 through 5.

The process claims do not broadly cover every method of manufacturing febuxostat tablets. They require production of a tablet having the product characteristics specified in claim 6. A manufacturer that makes a tablet using a different febuxostat polymorph, a different particle-size distribution, or a different formulation may avoid these claims even if its process includes wet granulation.

Process claims create a potential evidentiary distinction. A finished generic tablet can be tested for the claimed product characteristics, but proving the precise manufacturing steps may require discovery of batch records, master manufacturing instructions, process validation documents, and regulatory submissions.

How strong is the patent estate for U.S. Patent 7,361,676?

The patent was technically narrow but commercially targeted. Its main strength was that it claimed a finished tablet containing a defined febuxostat solid form rather than merely claiming an optional manufacturing process.

Strengths

The XRPD pattern provides an objective identifier for crystal A.
The particle-size range links the solid form to tablet performance.
Claim 1 covers the finished dosage form, not only the manufacturing process.
Dependent claims capture common formulation choices used in commercial tablets.
The claims can potentially reach a product made outside the United States if the product is imported into the United States.

Weaknesses

The claims depend on analytical characterization of crystal form and particle size.
The supplied claim language does not state XRPD tolerances or a particle-size measurement method.
A generic manufacturer may design around the particle-size range.
A different polymorph or amorphous form may avoid the literal crystal-A limitation.
The formulation claims do not broadly cover all febuxostat tablets.
Prior-art risk would focus on earlier disclosures of febuxostat crystal forms, particle-size control, wet granulation, and tablets containing lactose or starch.

The most important validity questions would have involved anticipation and obviousness. A prior-art reference combining the same crystal form, particle-size range, and tablet formulation could directly threaten novelty. A reference disclosing crystal A and conventional tablet manufacture could support an obviousness challenge if the claimed particle-size range was viewed as routine optimization rather than a non-obvious performance window.

When did U.S. Patent 7,361,676 expire?

Public patent records identify a November 2001 priority date and a U.S. filing in November 2002. The patent issued on April 29, 2008. Its ordinary 20-year patent term therefore ran to approximately November 2022, subject to any patent-term adjustment recorded by the USPTO.[1]

The patent is no longer a live U.S. exclusivity barrier based on its ordinary term. A historical patent-status analysis should distinguish:

Item	Date or status
Earliest reported priority	November 2001
U.S. filing	November 2002
Grant	April 29, 2008
Nominal term endpoint	November 2022
Current commercial significance	Historical formulation patent; no ordinary present-day blocking term

A patent’s expiration does not remove its historical relevance. It can remain important in analyzing past generic launch timing, settlement economics, damages periods, and whether a commercial product was designed around the patent before expiry.

What was the Orange Book status of the patent?

U.S. Patent 7,361,676 was associated with the Uloric febuxostat product and the related FDA approval record. Uloric was approved under NDA 021856 for 40 mg and 80 mg tablets. The Orange Book records patent information submitted for approved drug products, but an Orange Book listing does not itself establish validity or infringement.[2]

For small-molecule products, an Orange Book-listed formulation patent can trigger a Paragraph IV certification dispute when a generic applicant asserts that the patent is invalid, unenforceable, or not infringed. The patent’s relevance depended on whether it was listed against the specific Uloric strength and dosage form and whether the generic applicant’s ANDA product implicated the listed claims.

The practical effect of expiry is substantial. Once the patent term ended, it could no longer support a new 30-month stay under the Hatch-Waxman framework. Any Paragraph IV litigation tied exclusively to this patent would lose forward-looking exclusionary value, although damages and historical litigation issues could remain.

Were there Paragraph IV challenges and generic-launch disputes?

Febuxostat generic development involved Hatch-Waxman activity surrounding Uloric’s active-ingredient, formulation, and method-of-use patent estate. Generic applicants commonly challenge listed patents through Paragraph IV certifications or seek approval after the relevant patents expire or are resolved.

A Paragraph IV challenge to U.S. Patent 7,361,676 would have focused on:

Whether the ANDA product contained crystal A;
Whether the XRPD pattern matched the claimed form;
Whether particle size fell within 12.9 to 26.2 μm;
Whether the product used wet granulation;
Whether the formulation contained the claimed excipients or binder;
Whether the claims were invalid for anticipation or obviousness.

A generic could reduce risk by using a different polymorph, changing milling conditions, moving outside the claimed particle-size range, or selecting a formulation that omitted the claim-specific excipients. Regulatory equivalence to Uloric would not automatically require use of the patented formulation.

FDA approval of generic febuxostat products created competition after the principal Uloric exclusivity barriers ceased to block approval. The relevant commercial question was therefore not simply whether a generic was bioequivalent, but whether its CMC package used the same crystal form and particle-size characteristics.

Which companies controlled the febuxostat patent and commercial rights?

Teijin developed febuxostat and is associated with the underlying febuxostat intellectual-property portfolio. Takeda commercialized Uloric in the United States through licensing and commercialization arrangements involving Teijin. The patent owner, NDA holder, licensee, and commercial distributor should be distinguished in any assignment or litigation analysis.

The patent landscape included separate categories:

Patent category	Typical subject matter	Relevance to U.S. 7,361,676
Composition-of-matter patents	Febuxostat molecule and chemical derivatives	Broader but earlier-expiring protection
Crystal-form patents	Specific febuxostat polymorphs	Directly relevant
Formulation patents	Tablets, excipients, dissolution, particle size	Directly relevant
Process patents	Crystallization, milling, granulation, coating	Potentially relevant
Method-of-use patents	Treating gout or hyperuricemia	Separate infringement theory
Regulatory exclusivity	NDA exclusivity and pediatric exclusivity	Separate from patent term

A complete freedom-to-operate analysis must review the entire U.S. family and Orange Book record rather than treating U.S. Patent 7,361,676 as the entire febuxostat estate.

What generic design-around strategies apply?

The most direct design-around options are:

Use a febuxostat polymorph with a different XRPD pattern.
Use crystal A but maintain an average particle diameter outside the 12.9 to 26.2 μm range.
Use a different excipient system.
Replace hydroxypropyl cellulose with another binder.
Use a non-polyethylene-glycol coating.
Avoid wet granulation and use direct compression or dry granulation.

The strongest design-around must avoid the independent claim, not merely a dependent claim. Replacing polyethylene glycol would avoid claim 5 but would not avoid claim 1. Replacing lactose would avoid claim 3 but would not avoid claim 1 if all other claim 1 elements remained present.

A formulation using crystal A outside the particle-size range presents a more consequential design-around because the particle-size limitation appears in both the product and process independent claims.

Does biosimilar risk apply to this patent?

No. Febuxostat is a chemically synthesized small molecule, not a biologic. The relevant pathway is an ANDA under section 505(j) of the Federal Food, Drug, and Cosmetic Act, not a biosimilar application under the Public Health Service Act.

The competitive risks are generic substitution, abbreviated applications, formulation design-arounds, and possible authorized-generic competition. Biosimilar interchangeability, biologic reference-product exclusivity, and the Purple Book are not applicable.

What patent litigation affects U.S. Patent 7,361,676?

The relevant litigation framework is Hatch-Waxman litigation involving Uloric and generic febuxostat applicants. A litigation assessment should separate:

Cases challenging the active-ingredient patent;
Cases challenging crystal-form patents;
Cases involving tablet or formulation patents;
Method-of-use litigation;
Settlement agreements governing launch dates;
Administrative patent proceedings, if any;
Post-expiry disputes over damages or pre-expiry sales.

The expiration of U.S. Patent 7,361,676 removes its prospective injunction value. It does not, by itself, resolve unrelated Uloric patents or any contractual launch restrictions in settlement agreements. A generic launch date may have been governed by the last surviving patent, a settlement license, pediatric exclusivity, or FDA review timing rather than by this patent alone.

Key Takeaways

U.S. Patent 7,361,676 covers febuxostat crystal A tablets, not febuxostat generally.
Claim 1 requires a defined XRPD pattern, a 12.9 to 26.2 μm average particle diameter, an excipient, and a disintegrant.
Claims 2 through 5 add wet granulation, specified excipients, hydroxypropyl cellulose, and polyethylene glycol coating.
Claims 6 through 10 cover methods for producing the claimed tablet.
The patent is narrow but commercially targeted at the Uloric tablet formulation.
Its nominal U.S. patent term ended in November 2022.
The patent is not a current ordinary U.S. barrier to generic febuxostat approval.
The main historical design-around routes were a different polymorph, a different particle-size range, and a different formulation process.
Febuxostat is a small molecule, so biosimilar rules do not apply.
Current freedom-to-operate analysis must review the full febuxostat patent family, Orange Book listings, litigation history, and settlement terms.

FAQs

What is crystal A in U.S. Patent 7,361,676?

Crystal A is a defined crystalline form of febuxostat identified by the claimed XRPD diffraction peaks. The chemical identity alone is insufficient to establish that a sample is crystal A.

Can a febuxostat tablet infringe if it does not use wet granulation?

Yes. Claim 1 does not require wet granulation. A tablet can potentially infringe claim 1 without infringing claim 2 or claim 7.

Does using the same febuxostat molecule create infringement risk?

Not by itself. The patent claims a particular crystal form, particle-size range, tablet structure, and, in dependent claims, specified formulation or manufacturing characteristics.

Can a generic use crystal A after the patent expires?

Yes, subject to other unexpired patents, regulatory requirements, and applicable contractual restrictions. Expiration of this patent does not establish freedom from the entire febuxostat patent estate.

Is U.S. Patent 7,361,676 a composition-of-matter patent?

No. It is a formulation and manufacturing patent directed to tablets containing a specified febuxostat crystal form and particle-size range. Composition-of-matter protection belongs to separate febuxostat patents.

References

United States Patent and Trademark Office. (2008). U.S. Patent No. 7,361,676, Pharmaceutical composition comprising febuxostat. Patent Center and Patent Examination Data System.
U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations: Orange Book. FDA.
U.S. Food and Drug Administration. (2009). Uloric (febuxostat) prescribing information, NDA 021856. FDA.
U.S. Food and Drug Administration. (n.d.). Drugs@FDA: Uloric and associated regulatory records. FDA.
United States Code. (2023). 35 U.S.C. §§ 154, 271, and 282. Legal Information Institute, Cornell Law School.

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Japan	2002-090889	Mar 28, 2002

PCT Information
PCT Filed	March 28, 2003	PCT Application Number:	PCT/JP03/03962
PCT Publication Date:	October 09, 2003	PCT Publication Number:	WO03/082279

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	1488790	⤷ Start Trial	C20140037 00152	Estonia	⤷ Start Trial
Australia	2003220909	⤷ Start Trial
Canada	2474674	⤷ Start Trial
China	101836978	⤷ Start Trial
China	1642546	⤷ Start Trial
Cyprus	1115490	⤷ Start Trial
Denmark	1488790	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 7,361,676

Summary for Patent: 7,361,676