Details for Patent: 7,727,993

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Which drugs does patent 7,727,993 protect, and when does it expire?

Patent 7,727,993 protects NOURIANZ and is included in one NDA.

This patent has thirty-six patent family members in fifteen countries.

Summary for Patent: 7,727,993

Title:	Administering adenosine A2A receptor antagonist to reduce or suppress side effects of parkinson's disease therapy
Abstract:	The present invention is directed to methods of treating movement disorders by administering an effective amount of one or more adenosine A2A receptor antagonists to a patient in need thereof. The present invention also provides methods of decreasing the adverse effects of L-DOPA in patients receiving L-DOPA therapy in the treatment of Parkinson's disease. The present invention further provides methods and compositions for treating Parkinson's disease patients with sub-clinically effective doses of L-DOPA by combining L-DOPA treatment with an effective amount of one or more adenosine A2A receptor antagonists (i.e., L-DOPA sparing effect). The present invention further provides methods of effective treatment of Parkinson's disease by co-administering at least one adenosine A2A receptor antagonist, L-DOPA and a dopamine agonist and/or a COMT inhibitor and/or a MAO inhibitor. The present invention further provides methods of prolonging effective treatment of Parkinson's disease by administering an adenosine A2A receptor antagonist singly or together with a dopamine agonist, and/or a COMT inhibitor, and/or a MAO inhibitor without prior or subsequent administration of L-DOPA, delaying or removing on-set of L-DOPA motor complication.
Inventor(s):	Hiroshi Kase, Akihisa Mori, Yutaka Waki, Yutaka Ohsawa, Akira Karasawa, Yoshihisa Kuwana
Assignee:	Kyowa Kirin Co Ltd
Application Number:	US11/326,414
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 7,727,993
Patent Claim Types: see list of patent claims	Use;

U.S. Patent 7,727,993: Istradefylline L-DOPA Combination-Use Claims and Patent Landscape

U.S. Patent No. 7,727,993 protects the use of istradefylline, also known as KW-6002, with ongoing L-DOPA therapy in Parkinson's disease patients to reduce motor complications. The patent does not claim istradefylline as a chemical compound, a tablet formulation, or a manufacturing process. Its principal value is a method-of-use claim directed to reducing L-DOPA-associated motor complications, including OFF time, wearing-off, ON/OFF fluctuations, and dyskinesia.

The broadest claim requires four elements: a human patient, Parkinson's disease, current L-DOPA therapy, and administration of istradefylline or a pharmaceutically acceptable salt in an amount effective to reduce or suppress an adverse effect of L-DOPA therapy. The patent is associated with the U.S. regulatory and commercial protection for Nourianz, Kyowa Kirin's istradefylline product.

What drug and therapeutic use does U.S. Patent 7,727,993 protect?

The claimed active ingredient is istradefylline:

Attribute	Information
Generic name	Istradefylline
Development code	KW-6002
Chemical class	Adenosine A2A receptor antagonist
Claimed chemical form	(E)-8-(3,4-dimethoxystyryl)-1,3-diethyl-7-methylxanthine
Therapeutic setting	Parkinson's disease
Combination therapy	Ongoing L-DOPA therapy
Claimed benefit	Reduction or suppression of L-DOPA-related adverse effects
Key motor complications	OFF time, wearing off, ON/OFF fluctuations, dyskinesia
U.S. product	Nourianz tablets
U.S. sponsor	Kyowa Kirin Co., Ltd.

Istradefylline is administered as an adjunct to levodopa/carbidopa. The FDA approved Nourianz in 2019 as an adjunctive treatment to levodopa/carbidopa in adult patients with Parkinson's disease experiencing "OFF" episodes.[1]

The patent therefore sits between two categories of intellectual-property protection:

1. Earlier compound and composition patents covering istradefylline itself.
2. Later or separate patents covering the use of istradefylline with L-DOPA to address motor complications.

U.S. Patent 7,727,993 is in the second category.

What is the scope of claim 1 of U.S. Patent 7,727,993?

Claim 1 is the controlling independent claim. It recites:

A method of reducing or suppressing adverse effects from L-DOPA therapy, comprising administering, to a human patient with Parkinson's disease, an effective amount of istradefylline or a pharmaceutically acceptable salt thereof, wherein the patient currently receives L-DOPA therapy.

The claim contains the following limitations:

Claim limitation	Scope
Method claim	Liability generally turns on performance of the claimed treatment method
Human patient	Animal or in vitro uses are outside the literal claim
Parkinson's disease	The patient must have Parkinson's disease
Current L-DOPA therapy	Istradefylline must be administered while the patient is receiving L-DOPA therapy
Specific active ingredient	The compound must be istradefylline or a pharmaceutically acceptable salt
Effective amount	The administered amount must be effective to reduce or suppress an L-DOPA adverse effect
Therapeutic result	The treatment must be directed to reducing or suppressing an adverse effect from L-DOPA

The claim is narrower than a claim to administering istradefylline to any Parkinson's disease patient. A product used for Parkinson's disease without concurrent L-DOPA therapy would not satisfy the express "currently receives said L-DOPA therapy" limitation.

The claim also does not require a particular dose, dosage form, administration frequency, or brand. A generic istradefylline tablet, capsule, or other dosage form could fall within the claim if it is used in the claimed patient population and therapeutic setting.

What do claims 2 through 12 add?

Claims 2 through 12 are dependent claims. They narrow claim 1 by identifying specific L-DOPA motor complications or repeating those outcomes in more specific combinations.

Claim	Added limitation
2	Patient suffers from L-DOPA-induced motor complications
3	OFF time in motor fluctuations is reduced
4	Dyskinesias in motor complications are improved
5	OFF time in motor fluctuations is reduced
6	Dyskinesias in motor complications are improved
7	Adverse effect comprises ON/OFF fluctuations
8	Adverse effect comprises wearing-off phenomenon
9	Adverse effect comprises dyskinesia
10	Motor complications include ON/OFF fluctuations
11	Motor complications include wearing-off phenomenon
12	Motor complications include dyskinesia

Claims 3 and 5 are substantially overlapping in subject matter, as are claims 4 and 6. The distinction is that claims 3 and 4 depend from claim 2, while claims 5 and 6 depend directly from claim 1. Claims 7 through 12 provide additional fallback positions for specific manifestations of L-DOPA-related motor complications.

A product or treatment practice that falls outside a specific dependent claim may still infringe claim 1 if all limitations of claim 1 are satisfied.

Is U.S. Patent 7,727,993 a compound, formulation, or method-of-use patent?

It is a method-of-use patent.

Patent category	Covered by the asserted claims?	Reason
Istradefylline chemical compound	No	The claims assume the compound and regulate its therapeutic use
Pharmaceutically acceptable salt	Yes, but only as part of the method	Claim 1 expressly includes the salt form
Tablet formulation	No express formulation limitation	No excipient, release profile, strength, or composition is recited
Manufacturing process	No	No synthesis or purification step is claimed
Parkinson's disease treatment	Yes	The patient must have Parkinson's disease
L-DOPA combination therapy	Yes	Concurrent L-DOPA therapy is mandatory
OFF-time reduction	Yes, in dependent claims	Claims 3 and 5 identify this result
Dyskinesia improvement	Yes, in dependent claims	Claims 4 and 6 identify this result
Wearing-off treatment	Yes, in dependent claims	Claims 8 and 11 identify this adverse effect
ON/OFF fluctuation treatment	Yes, in dependent claims	Claims 7 and 10 identify this adverse effect

The absence of a dose limitation expands the claim's potential reach across different istradefylline strengths, provided the administered amount is effective for the claimed purpose.

What is the patent term and expiration date for U.S. Patent 7,727,993?

U.S. Patent 7,727,993 issued on May 25, 2010. Public patent records and FDA patent-listing information associate the patent with an expiration date in 2027, reflecting patent-term adjustment rather than only the ordinary 20-year term calculated from the relevant U.S. filing date.[2][3]

Event	Date
U.S. patent issued	May 25, 2010
Patent number	7,727,993
Patent type	Method of use
Listed product association	Nourianz
Reported expiration	May 27, 2027
Regulatory significance	Use-patent protection for istradefylline with L-DOPA

The May 27, 2027 date should be treated as the operative listed expiration for U.S. commercial planning unless a later terminal disclaimer, patent-term adjustment correction, court order, or USPTO record changes the term. Patent expiration does not eliminate other patents that may cover the product, formulation, or separate use.

What is the Orange Book status of U.S. Patent 7,727,993?

U.S. Patent 7,727,993 has been listed in connection with Nourianz, the FDA-approved istradefylline product. Its listing identifies a method of use rather than a drug substance or drug-product patent.[3]

An Orange Book use-code listing can affect an abbreviated new drug application even when the generic applicant does not seek approval for every patented use. Under the Hatch-Waxman framework, a generic applicant may submit a section viii statement for a patented method of use and seek approval only for non-patented indications. The practical effect depends on the Orange Book use code, the proposed labeling, and whether the generic label omits the patented use.

For this patent, the commercial risk is highest when a generic label expressly includes:

• Adjunctive use with levodopa/carbidopa;
• Reduction of OFF episodes;
• Treatment of wearing-off;
• Reduction of ON/OFF fluctuations; or
• Improvement of L-DOPA-induced dyskinesia.

A label directed only to an unpatented use would create a different analysis, but a generic applicant cannot avoid infringement merely by removing promotional language if the approved label still instructs use in the patented method.

How do Paragraph IV challenges apply to this patent?

A generic applicant seeking approval before the listed patent expires could address U.S. Patent 7,727,993 through a Paragraph IV certification. The applicant would assert that the patent is invalid, unenforceable, or not infringed.[4]

The principal Paragraph IV theories would likely involve:

Non-infringement

A generic applicant could argue that its proposed label does not instruct the claimed combination-use method. Potential arguments would focus on whether the label requires:

• Concurrent L-DOPA therapy;
• Treatment of a Parkinson's disease patient;
• Reduction of an L-DOPA adverse effect; and
• Use of istradefylline for the claimed purpose.

A label that includes adjunctive treatment of OFF episodes would present a stronger infringement risk than a label limited to a separate, non-L-DOPA use.

Invalidity

Potential invalidity arguments would include:

• Lack of novelty;
• Obviousness based on earlier xanthine, adenosine A2A antagonist, and Parkinson's disease disclosures;
• Written-description or enablement defects;
• Indefiniteness relating to "effective amount" or "adverse effects."

The claim's use of a specific compound and specific patient-treatment context may strengthen its distinction over broad prior-art disclosures. The patent's validity would depend on the prior art available as of its effective filing date and the evidentiary record developed in litigation.

Section viii carve-out

A generic applicant could attempt to omit the patented method from its labeling. This route is more difficult where the reference product's principal or only approved use is the same L-DOPA adjunctive therapy protected by the patent. The regulatory viability of a carve-out depends on the FDA-approved labeling and the exact Orange Book use code.

Declaratory and enforcement litigation

A Paragraph IV notice could trigger a patent-infringement action by the patent owner. Under 21 U.S.C. § 355(j)(5)(B)(iii), timely litigation can create a 30-month stay of ANDA approval, subject to statutory exceptions and court rulings.[4]

What patent landscape surrounds istradefylline and Nourianz?

The patent estate should be separated into four groups.

Estate category	Typical subject matter	Relevance to U.S. Patent 7,727,993
Core compound patents	Istradefylline and related xanthine derivatives	Separate from the asserted method claims
Therapeutic-use patents	Parkinson's disease, L-DOPA adjunctive treatment, OFF episodes	Directly relevant
Formulation patents	Tablet composition, solid-state form, dissolution, stability	Relevant to product-specific generic strategy
Process patents	Synthesis, purification, crystallization, intermediates	May create manufacturing barriers but do not expand claim 1

The main patent-expiration risk cannot be assessed from Patent 7,727,993 alone. A generic may avoid a formulation or process patent but still face the method-of-use patent. Conversely, expiration or invalidation of the method patent would not necessarily eliminate later-expiring formulation or solid-form rights.

What formulations are protected by this patent?

None are expressly protected by the supplied claims.

The claims do not specify:

• 20 mg or 40 mg strength;
• Immediate-release or extended-release delivery;
• Particular excipients;
• Tablet coating;
• Particle size;
• Crystalline form;
• Dissolution profile;
• Bioavailability threshold; or
• Manufacturing method.

A formulation could still be commercially protected by a separate patent. That separate protection would need to be analyzed independently through the relevant patent claims, Orange Book listing, and prosecution history.

The absence of a formulation limitation makes claim 1 potentially applicable to multiple dosage forms. It also means that a generic cannot avoid the claim solely by changing excipients or tablet design if the generic product is labeled for the patented therapeutic use.

How strong is the patent estate for U.S. Patent 7,727,993?

The patent has meaningful commercial strength because it targets the principal clinical use of istradefylline in the United States: adjunctive treatment with levodopa/carbidopa for OFF episodes.

Strengths

1. The claim identifies a specific active ingredient rather than a broad pharmacological class.
2. The combination with current L-DOPA therapy is clinically concrete.
3. The claim covers the treatment context associated with FDA-approved Nourianz use.
4. The absence of a specified dose makes design-around through dose selection difficult.
5. Dependent claims identify commercially recognizable motor complications.

Weaknesses and litigation pressure points

1. It is a method-of-use patent, so infringement depends heavily on labeling and instructions.
2. A generic may pursue a section viii carve-out if the regulatory record permits.
3. "Effective amount" and "reducing or suppressing adverse effects" may create factual disputes.
4. Prior-art clinical disclosures could support obviousness arguments.
5. The claims may not reach uses of istradefylline outside concurrent L-DOPA therapy.
6. The patent does not independently block alternative formulations or manufacturing routes.

The strongest enforcement position would arise against a generic label that reproduces the Nourianz indication and specifically instructs treatment of OFF episodes during levodopa therapy.

Which companies are most likely to challenge istradefylline exclusivity?

The relevant challenger group consists of generic manufacturers with Parkinson's disease portfolios and the capacity to file ANDAs for istradefylline tablets. Potential entrants may include large U.S. generic companies and specialty generic firms, but a definitive list of current Paragraph IV filers requires the FDA litigation docket, district-court complaints, ANDA litigation records, and current Orange Book data.

The commercial entry question has three separate components:

Question	Business effect
Is there a Paragraph IV filing?	Determines whether early litigation may occur
Is the patented use carved out?	Determines whether a generic can receive approval before patent expiry
Are formulation or solid-form patents listed?	Determines whether non-use patent barriers remain

No reliable conclusion should be drawn from an ANDA filing alone. A company may file an ANDA with a Paragraph IV certification, a section viii statement, or a Paragraph III certification tied to patent expiration.

What is the likely generic launch scenario?

The most likely launch paths are:

Launch after May 2027

A generic may launch after expiration of the relevant use patent, subject to any other unexpired Orange Book patents and regulatory exclusivity. This is the lowest litigation-risk scenario.

At-risk launch before expiration

A generic could launch before May 2027 after prevailing in litigation, obtaining a favorable settlement, or accepting infringement exposure. This path carries damages and injunction risk.

Carved-out label

A generic may seek approval with the patented L-DOPA-related use omitted. This strategy depends on whether the remaining label has a lawful, medically meaningful use and whether the FDA accepts the proposed carve-out.

Authorized generic or settlement entry

The patent holder could license or authorize entry before patent expiration. Settlement terms may include a negotiated launch date, supply arrangement, or authorized-generic structure. The terms of any such agreement should be reviewed for FTC reporting, antitrust restrictions, and the exact scope of any release.

What is the competitive landscape for Parkinson's disease motor complications?

Istradefylline competes with other adjunctive treatments used to reduce OFF time in patients receiving levodopa therapy.

Product or class	Principal role	Relationship to istradefylline
Istradefylline	Adenosine A2A antagonist adjunctive therapy	Subject of U.S. Patent 7,727,993
MAO-B inhibitors	Adjunctive control of motor fluctuations	Pharmacologic alternatives
COMT inhibitors	Extend levodopa effect	Compete for OFF-time management
Dopamine agonists	Adjunctive dopaminergic therapy	Alternative or complementary treatment
Amantadine products	Dyskinesia management	More directly focused on dyskinesia
Infusion and device therapies	Advanced motor-fluctuation management	Compete in later-stage disease

Patent expiry may increase price competition, but substitution will depend on physician preference, adverse-effect profiles, formulary placement, dosing convenience, and the relative value of OFF-time reduction versus dyskinesia control.

What revenue exposure does the patent create?

The patent is commercially important because its claimed use overlaps with the labeled indication of Nourianz. Revenue exposure is therefore tied to the proportion of product sales generated by patients receiving concurrent levodopa therapy and treated for OFF episodes.

Key exposure variables include:

• U.S. Nourianz net sales;
• Market share held by Kyowa Kirin;
• Number and timing of ANDA filings;
• Whether challengers obtain tentative approval;
• Whether a carve-out is accepted;
• Other Orange Book patents;
• Payer substitution after generic launch;
• Availability of authorized generic supply.

A method-of-use patent can protect revenue even when the active ingredient itself is no longer covered by a composition patent. Its practical value is highest when the patented indication accounts for nearly all commercially viable use.

Does this patent create biosimilar risk?

No. Biosimilar law does not apply to istradefylline because istradefylline is a small-molecule drug. The relevant competitive threat is an ANDA-based generic, not a biosimilar under the Biologics Price Competition and Innovation Act.

The applicable regulatory pathway is section 505(j) of the Federal Food, Drug, and Cosmetic Act. Patent disputes are governed by the Hatch-Waxman framework, including Paragraph IV certifications and potential 30-month stays.[4]

What manufacturing and geographic barriers remain?

U.S. Patent 7,727,993 does not claim a manufacturing process. A manufacturer may therefore be able to synthesize istradefylline through a non-infringing process, subject to separate process, intermediate, purification, solid-form, and formulation patents.

Geographic protection is also separate from U.S. protection:

• U.S. Patent 7,727,993 controls only U.S. patent rights.
• Foreign counterparts may have different claims and expiration dates.
• Some foreign patents may have lapsed, been abandoned, or been narrowed.
• Regulatory exclusivity and patent listing practices vary by jurisdiction.

International launch planning requires country-by-country review of national-phase patents, supplementary protection certificates, data exclusivity, and local product approvals.

What is the litigation and settlement status?

The supplied claims establish the patent's subject matter but do not establish a current Paragraph IV complaint, settlement, license, or court judgment. Patent status should be distinguished from litigation status:

Status question	Determination from the supplied record
Patent issued?	Yes
Claims directed to L-DOPA adjunctive use?	Yes
Orange Book relevance?	Yes, in connection with Nourianz use protection
Paragraph IV challenge identified?	Not established by the supplied record
Settlement agreement identified?	Not established by the supplied record
Invalidity judgment identified?	Not established by the supplied record
Infringement judgment identified?	Not established by the supplied record

Key Takeaways

1. U.S. Patent 7,727,993 is a method-of-use patent for istradefylline administered to Parkinson's disease patients currently receiving L-DOPA therapy.
2. The principal protected outcomes are reduced OFF time, reduced wearing off, fewer ON/OFF fluctuations, and improved dyskinesia.
3. The patent does not claim the istradefylline molecule, a particular tablet, a formulation, or a manufacturing process.
4. The reported U.S. expiration date is May 27, 2027.
5. Generic risk depends heavily on the proposed label, Orange Book use code, Paragraph IV strategy, and potential section viii carve-out.
6. Biosimilar risk is not relevant because istradefylline is a small molecule.
7. Separate formulation, solid-form, process, or later method-of-use patents could extend commercial barriers beyond this patent.
8. A generic product labeled for adjunctive OFF-episode treatment during levodopa therapy would present the greatest infringement exposure.

FAQs

Can a generic avoid U.S. Patent 7,727,993 by using a different istradefylline dose?

Probably not if the dose remains an effective amount and the product is labeled for the claimed L-DOPA adjunctive use. Claim 1 does not specify a particular dose.

Does changing the tablet excipients avoid the patent?

No. The claims contain no excipient or formulation limitation. A formulation change would not avoid the method claim if the treatment instructions remain within its scope.

Does the patent cover istradefylline monotherapy?

No. Claim 1 requires that the patient currently receive L-DOPA therapy. Istradefylline use without concurrent L-DOPA would not satisfy that express limitation.

Is dyskinesia treatment the only use protected by the patent?

No. The claims also cover broader adverse effects from L-DOPA therapy and specifically identify OFF time, ON/OFF fluctuations, and wearing-off phenomenon.

Can a company sell istradefylline for an unpatented indication before May 2027?

Potentially, if the product labeling and actual instructions do not practice the patented method and no separate patent blocks the use. The regulatory feasibility depends on the FDA-approved labeling and Orange Book use-code requirements.

References

1. U.S. Food and Drug Administration. (2019). Nourianz (istradefylline) prescribing information.
2. United States Patent and Trademark Office. (2010). U.S. Patent No. 7,727,993: Methods for reducing adverse effects from L-DOPA therapy.
3. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book.
4. Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 355(j).

Drugs Protected by US Patent 7,727,993

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			A METHOD OF REDUCING OFF TIME FROM L-DOPA THERAPY, COMPRISING ADMINISTERING, TO A HUMAN PATIENT WITH PARKINSON'S DISEASE, AN EFFECTIVE AMOUNT OF ISTRADEFYLLINE, WHEREIN THE PATIENT CURRENTLY RECEIVES SAID L-DOPA THERAPY
Kyowa Kirin	NOURIANZ	istradefylline	TABLET;ORAL	022075-002	Aug 27, 2019		RX	Yes	Yes			Y			A METHOD OF REDUCING OFF TIME FROM L-DOPA THERAPY, COMPRISING ADMINISTERING, TO A HUMAN PATIENT WITH PARKINSON'S DISEASE, AN EFFECTIVE AMOUNT OF ISTRADEFYLLINE, WHEREIN THE PATIENT CURRENTLY RECEIVES SAID L-DOPA THERAPY

International Family Members for US Patent 7,727,993

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2003207734
Australia	2008200611
Brazil	0306919