Details for Patent: 8,318,201

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Which drugs does patent 8,318,201 protect, and when does it expire?

Patent 8,318,201 protects NOURIANZ and is included in one NDA.

This patent has thirteen patent family members in ten countries.

Summary for Patent: 8,318,201

Title:	Method of stabilizing diarylvinylene compound
Abstract:	(wherein Y1 and Y2 may be the same or different and each represents a hydrogen atom, halogen or lower alkyl; and Z and A may be the same or different and each represents substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl) The present invention provides, for example, a method for stabilization of a diarylvinylene compound such as a compound represented by the above formula (I) or the like, or a pharmaceutically acceptable salt thereof in a solid formulation containing the diarylvinylene compound or the pharmaceutically acceptable salt thereof, which comprises allowing an inorganic substance and/or a colorant to exist in the solid formulation, and the like.
Inventor(s):	Akihiro Uchida, Yasuhiro Ishikawa, Yasuhiko Ueno, Kiichiro Kaji, Masaharu Aimoto, Naoki Kaneko
Assignee:	Kyowa Kirin Co Ltd
Application Number:	US10/528,451
Patent Claim Types: see list of patent claims	Use; Composition; Formulation;

US Patent 8,318,201: Istradefylline Iron-Oxide Formulation Patent Scope and Patent Landscape

US Patent 8,318,201 protects solid formulations of istradefylline that contain iron oxide to suppress dimerization-related impurities. The patent does not broadly claim istradefylline as a molecule, Parkinson's disease treatment, or every formulation. Its commercial value is concentrated in coated tablets and other solid dosage forms using iron oxide within specified concentration ranges.

The patent was assigned to Kyowa Hakko Kirin-related entities and supports the formulation protection for NOURIANZ, the FDA-approved istradefylline product. Its principal risk period extends through the patent's reported 2027 term, subject to the applicable Orange Book expiration and any patent-term adjustment.

What drug and impurity problem does US Patent 8,318,201 cover?

The claimed active ingredient is istradefylline, also known as KW-6002. Its chemical description is:

(E)-8-(3,4-dimethoxystyryl)-1,3-diethyl-7-methyl-3,7-dihydro-1H-purine-2,6-dione

Istradefylline is an adenosine A2A receptor antagonist used with levodopa/carbidopa for reduction of "off" episodes in adults with Parkinson's disease. The FDA approved NOURIANZ on Aug. 27, 2019, under NDA 212489. The product is marketed by Kyowa Kirin, Inc. (FDA, 2019).

The patent addresses chemical instability in solid formulations. Istradefylline can undergo dimerization, producing impurities during storage or processing. US 8,318,201 claims the use of iron oxide as an impurity-suppressing component.

The patent is therefore an excipient and formulation-stability patent, not a basic compound patent.

What does claim 1 of US 8,318,201 require?

Claim 1 requires all of the following:

1. A pharmaceutical composition.
2. A solid formulation.
3. Istradefylline or a pharmaceutically acceptable salt.
4. Iron oxide in the solid formulation.
5. Suppression of impurities caused by dimerization of istradefylline.

The claim is written as a method claim. It covers a method of suppressing dimerization impurities by providing iron oxide in the solid formulation.

The operative limitation is the presence of iron oxide. A generic solid tablet containing istradefylline would not necessarily fall within claim 1 unless the formulation also contains iron oxide and meets the claim's functional requirement.

Claim 1 scope

Element	Scope
Active ingredient	Istradefylline or pharmaceutically acceptable salt
Dosage form	Solid formulation
Required excipient	Iron oxide
Protected technical effect	Suppression of dimerization impurities
Claim type	Method of stabilizing a pharmaceutical composition
Excluded subject matter	Liquid formulations, formulations without iron oxide, unrelated xanthine compounds

The claim does not require a particular tablet strength, release profile, coating process, tablet shape, or treatment indication. Those limitations may be relevant to infringement analysis only if they are imposed by dependent claims or the patent specification.

What formulations are protected by claims 2 through 6?

Claims 2 through 6 narrow the scope by defining a core-and-coating structure, inorganic excipients, and iron-oxide loading levels.

Claim 2: coated solid formulation

Claim 2 requires:

• a core containing istradefylline or its salt;
• optional conventional excipients; and
• a coated layer containing iron oxide.

The core may contain a diluent, binder, disintegrant, lubricant, surfactant, plasticizer, or inorganic substance.

This claim is directed to a dosage form in which the iron oxide is in the coating rather than merely being dispersed throughout the tablet core. A tablet with an istradefylline core and iron-oxide-containing film coating is the clearest commercial embodiment.

Claim 3: additional inorganic substances

Claim 3 limits the coating to iron oxide plus at least one listed inorganic substance. The listed materials include:

• titanium oxide;
• zinc oxide;
• magnesium oxide;
• talc;
• magnesium silicate;
• synthetic aluminum silicate;
• magnesium carbonate;
• calcium sulfate;
• aluminum sulfate; and
• barium sulfate.

This claim can cover conventional film-coating systems in which iron oxide is combined with pigments, opacifiers, fillers, or mineral processing aids.

Claim 4: iron-oxide concentration

Claim 4 requires the coating to contain 0.01 to 70 parts by weight of iron oxide per 100 parts by weight of the coated layer.

This is a broad range. It captures trace levels at the lower end and heavily pigmented coatings at the upper end.

Claim 5: combined inorganic-material limitation

Claim 5 adds two limitations:

• iron oxide at 0.01 to 70 parts by weight per 100 parts of coating; and
• total inorganic substance plus iron oxide at 0.01 to 90 parts by weight per 100 parts of coating.

A formulation must satisfy both the iron-oxide range and the combined inorganic-material ceiling.

Claim 6: iron oxide relative to active ingredient

Claim 6 covers formulations containing 0.001 to 10,000 parts by weight of iron oxide per 100 parts by weight of istradefylline or its salt.

This is an exceptionally broad active-to-excipient ratio. It can capture very low iron-oxide loading relative to active ingredient and formulations containing iron oxide in substantial excess of the active ingredient.

How broad is the enforceable scope of US 8,318,201?

The broadest practical claim is claim 1. It does not require the iron oxide to be in a coating, does not specify a particular iron-oxide polymorph or color, and does not impose a numerical concentration.

Claims 2 through 6 provide fallback positions with greater structural and quantitative specificity.

Claim	Principal limitation	Relative scope
1	Solid istradefylline formulation containing iron oxide and suppressing dimerization impurities	Broadest
2	Istradefylline core with iron-oxide-containing coating	Narrower
3	Coating also contains specified inorganic substance	Narrower
4	Iron oxide is 0.01-70 wt. parts per 100 parts coating	Narrower
5	Iron oxide and total inorganic substances within stated ranges	Narrower
6	Iron oxide is 0.001-10,000 parts per 100 parts active	Quantitative fallback

The principal claim-construction issue is whether the "suppressing" limitation is treated as a required result that must be demonstrated in the accused product or as a functional description of the claimed formulation. The patent specification, prosecution history, and laboratory evidence would be important in a litigation context.

A second issue is whether the method claim requires an affirmative manufacturing or formulation step. A company that makes, sells, or imports a product containing the claimed formulation could face induced or contributory infringement theories even where direct performance of the stabilization method is performed during manufacture.

What is the patent expiration date for US 8,318,201?

US 8,318,201 issued on Nov. 27, 2012. The relevant patent family has a reported term extending into December 2027. Public patent records identify Dec. 17, 2027, as the expected expiration date for the US patent family record, before any applicable patent-term adjustment.

The patent term runs from the relevant US nonprovisional or international filing date, not from the grant date. The Orange Book patent record is the controlling commercial reference for FDA-listed expiration data.

Event	Date
US patent grant	Nov. 27, 2012
FDA approval of NOURIANZ	Aug. 27, 2019
Reported patent expiration	Dec. 17, 2027
NCE exclusivity period	Through Aug. 27, 2024
Product type	Small-molecule drug

The patent's remaining life is materially longer than the product's FDA new chemical entity exclusivity. After regulatory exclusivity ended, generic applicants could pursue ANDA filing strategies, subject to listed patents and Paragraph IV certification rules.

What is the Orange Book status of US 8,318,201?

US 8,318,201 is associated with the FDA-approved NOURIANZ product and has been identified in public FDA patent-listing data for istradefylline. Its importance is that it covers a formulation attribute likely to be present in the reference product rather than merely claiming an optional method of use.

An Orange Book listing does not establish infringement or validity. It does create a statutory framework for ANDA applicants that must address the listed patent through:

• Paragraph I certification;
• Paragraph II certification;
• Paragraph III certification; or
• Paragraph IV certification.

For an unexpired formulation patent, a Paragraph IV certification could trigger a patent-infringement action under 21 U.S.C. § 355(j)(5)(B)(iii). A timely suit could create a 30-month stay of ANDA approval, subject to statutory exceptions and litigation developments (FDA, 2024a; 21 U.S.C. § 355).

When does istradefylline lose exclusivity?

Istradefylline had several distinct forms of exclusivity:

Exclusivity or protection	Status
Five-year NCE exclusivity	Began Aug. 27, 2019; expired Aug. 27, 2024
Paragraph IV filing eligibility	Generally opened after four years, Aug. 27, 2023
Formulation patent protection	Extends into 2027 based on US 8,318,201
Biosimilar exclusivity	Not applicable
Pediatric exclusivity	Must be confirmed from the current FDA Orange Book record
Method-of-use protection	Separate analysis required for any listed use patent

NCE exclusivity prevents an ANDA or 505(b)(2) application relying on the reference drug's safety and efficacy data from being submitted during the first four years. A Paragraph IV ANDA may generally be submitted during the fifth year. The NCE exclusivity period does not override an unexpired formulation patent.

Which companies are challenging the istradefylline patent?

Publicly available records associated with US 8,318,201 do not establish a reported final judgment invalidating the patent, a public inter partes review decision canceling its claims, or a reported Paragraph IV settlement involving this specific patent.

The absence of a publicly identified challenge does not eliminate generic-entry risk. A generic applicant can:

• certify that it will not market until patent expiration;
• design around the iron-oxide limitation;
• challenge validity or enforceability;
• argue that its formulation does not suppress dimerization within the claim's meaning; or
• pursue a formulation that uses a different stabilizer or coating system.

Any definitive assessment of a specific ANDA challenge would require review of FDA litigation-stay records, district court complaints, PTAB filings, and current Orange Book updates.

How strong is the patent estate for NOURIANZ?

The estate's strongest feature is the alignment between the patent claims and a specific manufacturing or storage problem. The claims are not dependent on a broad therapeutic indication. They target formulation stability, which can be difficult to avoid if iron oxide is part of the reference product's coating system.

Its principal vulnerabilities are claim-specific.

Strengths

• Claim 1 reaches any solid istradefylline formulation containing iron oxide, if the claimed impurity-suppression result is established.
• Claim 2 targets a conventional core-and-film-coating architecture.
• Claim 6 provides a very broad active-to-iron-oxide ratio range.
• The claims address a measurable product-quality issue.
• The patent can remain relevant after NCE exclusivity expires.

Vulnerabilities

• The claims are limited to iron oxide.
• A generic developer may substitute another stabilizer, coating pigment, or mineral excipient.
• Prior-art risk may exist for using metal oxides as pharmaceutical stabilizers, pigments, or light barriers.
• The functional "suppression" limitation may create proof and claim-construction issues.
• Claims 4 through 6 may be vulnerable if the claimed concentration ranges lack sufficient technical distinction over prior art.
• The patent does not prevent a non-solid dosage form or a solid formulation that uses no iron oxide.

The estate is stronger against a copycat formulation than against a deliberate design-around.

What generic launch scenarios exist for istradefylline?

Scenario 1: Paragraph III certification

A generic applicant accepts the patent and agrees not to launch until expiration. Entry would generally be expected after the listed patent expires, subject to regulatory approval and other listed patents.

Scenario 2: Paragraph IV challenge

The applicant alleges that US 8,318,201 is invalid, unenforceable, or not infringed. Kyowa Kirin could sue within the statutory period, potentially delaying FDA approval for up to 30 months.

Scenario 3: iron-oxide design-around

The applicant develops a formulation using a different stabilizer or coating system. This is the most direct technical route around the patent, but the applicant must still address bioequivalence, impurity control, dissolution, manufacturability, and any other Orange Book-listed patents.

Scenario 4: non-infringing iron-oxide formulation

The applicant includes iron oxide but argues that the formulation does not meet the claimed functional limitation or falls outside the applicable dependent-claim ranges. This approach carries greater litigation risk than eliminating iron oxide.

What manufacturing and geographic barriers does the patent create?

US 8,318,201 is a US patent. Its direct exclusionary effect is limited to US manufacture, use, sale, offer for sale, and importation under US patent law.

The family may have corresponding applications or patents in other jurisdictions. Foreign rights must be assessed separately because:

• patent claims may differ;
• prosecution amendments may narrow foreign claims;
• patent terms may vary;
• some jurisdictions may have no granted counterpart; and
• national litigation and regulatory linkage rules differ.

The patent creates a manufacturing barrier where iron oxide is incorporated into the coating or solid dosage form. It is less significant for API manufacture because the claims do not cover production of istradefylline itself. The barrier is also less significant for a manufacturer producing a non-iron-oxide formulation outside the United States, unless that product is later imported into or sold in the United States.

How does US 8,318,201 compare with a compound patent?

Protection type	What it would cover	Relevance to NOURIANZ
Compound patent	Istradefylline molecule and salts	Broadest, but generally earlier-expiring
Method-of-treatment patent	Use of istradefylline for Parkinson's disease or off episodes	Relevant to labeled use
Formulation patent	Solid dosage form containing iron oxide	US 8,318,201
Manufacturing patent	Process for making istradefylline or dosage form	Could create separate process barriers
Polymorph patent	Specific crystalline form	Depends on product solid state
Regulatory exclusivity	FDA reliance restrictions	Expired for NCE purposes in 2024

US 8,318,201 is narrower than a composition-of-matter patent but can have commercial value after basic compound protection expires. Its practical importance depends on whether the reference product's formulation uses the claimed iron-oxide architecture and whether a generic can obtain equivalent stability without using iron oxide.

What licensing deals affect the patent?

The principal commercial relationship is Kyowa Kirin's ownership and commercialization of NOURIANZ in the United States. US 8,318,201 is associated with the Kyowa patent estate.

No publicly reported license or settlement specific to US 8,318,201 is established in the cited patent and FDA records. A separate commercial agreement could exist without changing the patent's listed owner, especially where rights are sublicensed, territory-specific, or held through an affiliated entity.

Key Takeaways

• US 8,318,201 protects iron-oxide-containing solid formulations of istradefylline.
• Claim 1 is the broadest claim and requires a solid formulation, istradefylline, iron oxide, and suppression of dimerization impurities.
• Claims 2 through 5 focus on coated tablets and specified inorganic excipients.
• Claim 6 covers a broad iron-oxide-to-active-ingredient ratio.
• The patent is a formulation-stability patent, not an istradefylline compound patent.
• The reported US patent term extends to Dec. 17, 2027.
• Istradefylline's five-year NCE exclusivity expired on Aug. 27, 2024.
• Biosimilar risk is not applicable because istradefylline is a small molecule.
• The principal generic strategy is to remove iron oxide or replace it with a different stabilizer or coating system.
• A Paragraph IV challenge could create litigation and a potential 30-month approval stay.
• The patent's commercial strength depends on the reference formulation, current Orange Book listing, claim construction, and the availability of a technically acceptable non-infringing formulation.

FAQs

Can a generic use titanium dioxide instead of iron oxide in an istradefylline tablet?

Potentially. Titanium dioxide alone would not satisfy the express iron-oxide limitation. The generic would still need to evaluate other patents, formulation equivalence, impurity formation, and any method-of-use claims.

Does US 8,318,201 cover istradefylline API manufacturing?

No. The claims provided are directed to solid pharmaceutical formulations and their stabilization. They do not claim the synthesis of istradefylline API.

Does the patent cover capsules containing istradefylline?

Possibly, if the capsule is a solid formulation containing iron oxide and satisfies claim 1. Claims requiring a core and coated layer would depend on whether the capsule structure meets those limitations.

Can a generic avoid the patent by omitting a coating?

Potentially. Omitting the coating may avoid claims 2 through 5, but claim 1 remains relevant if the solid formulation contains iron oxide and suppresses dimerization impurities.

Is a biosimilar application required for generic istradefylline?

No. Istradefylline is a chemically synthesized small molecule. A qualifying competitor would generally pursue an ANDA or, depending on the product and regulatory basis, a 505(b)(2) application rather than a biosimilar application.

References

1. Food and Drug Administration. (2019). FDA approves Nourianz for Parkinson's disease. U.S. Department of Health and Human Services.

2. Food and Drug Administration. (2024a). Approved drug products with therapeutic equivalence evaluations: Orange Book. U.S. Department of Health and Human Services.

3. Food and Drug Administration. (2024b). Nourianz (istradefylline) prescribing information. Kyowa Kirin, Inc.

4. United States Patent and Trademark Office. (2012). U.S. Patent No. 8,318,201, pharmaceutical composition. U.S. Department of Commerce.

5. 21 U.S.C. § 355. (2024). New drugs. United States Code.

6. 35 U.S.C. §§ 154, 271. (2024). Patent term and infringement. United States Code.

Drugs Protected by US Patent 8,318,201

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Kyowa Kirin	NOURIANZ	istradefylline	TABLET;ORAL	022075-001	Aug 27, 2019		RX	Yes	No			Y
Kyowa Kirin	NOURIANZ	istradefylline	TABLET;ORAL	022075-002	Aug 27, 2019		RX	Yes	Yes			Y

Foreign Priority and PCT Information for Patent: 8,318,201

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Japan	2003-336944	Sep 29, 2003

PCT Information
PCT Filed	September 29, 2004	PCT Application Number:	PCT/JP2004/014687
PCT Publication Date:	April 07, 2005	PCT Publication Number:	WO2005/030219

International Family Members for US Patent 8,318,201

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	046169
Australia	2004275646
Canada	2540109
China	1845742
European Patent Office	1676578
Spain	2534220