Details for Patent: 11,040,029

Which drugs does patent 11,040,029 protect, and when does it expire?

Patent 11,040,029 protects INGREZZA and INGREZZA SPRINKLE and is included in two NDAs.

This patent has eighty-nine patent family members in eleven countries.

Summary for Patent: 11,040,029

Title:	Methods for the administration of certain VMAT2 inhibitors
Abstract:	Provided are methods of administering a vesicular monoamine transport 2 (VMAT2) inhibitor chosen from valbenazine and (+)-α-3-isobutyl-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol, or a pharmaceutically acceptable salt and/or isotopic variant thereof, to a patient in need thereof wherein the patient is also being administered a strong cytochrome P450 2D6 (CYP2D6) inhibitor.
Inventor(s):	Christopher F. O'Brien, Haig P. Bozigian
Assignee:	Neurocrine Biosciences Inc
Application Number:	US16/870,572
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 11,040,029
Patent Claim Types: see list of patent claims	Use; Dosage form;

US Patent 11,040,029: Valbenazine CYP2D6 Dosing Claims, Scope, Expiration and Generic Risk

US Patent No. 11,040,029 protects a specific valbenazine treatment strategy for tardive dyskinesia when the patient is receiving a strong CYP2D6 inhibitor. The patent is directed to dose limitation, dose reduction, monitoring for exposure-related adverse reactions, and use of valbenazine ditosylate, including polymorphic Form I. It does not broadly claim valbenazine, VMAT2 inhibition, or tardive dyskinesia treatment generally.

The principal commercial relevance is Ingrezza, Neurocrine Biosciences' valbenazine product. The claims track the FDA labeling instruction to limit valbenazine to 40 mg once daily in patients receiving a strong CYP2D6 inhibitor. The patent therefore has meaningful Orange Book and ANDA litigation value, although its enforcement depends on the proposed generic's labeling and the evidence available to prove induced infringement.

What drug and product do the claims cover?

The chemical name in the claims identifies valbenazine, marketed as Ingrezza. The claimed active moiety is the valbenazine free base, while several dependent claims expressly cover pharmaceutically acceptable salts and the ditosylate salt.

Claim element	Commercial identification
VMAT2 inhibitor	Valbenazine
Active metabolite	(+)-alpha-HTBZ
Salt specifically claimed	Valbenazine ditosylate
Dosage form	Oral capsule
Covered disease	Tardive dyskinesia
Key interaction	Concomitant strong CYP2D6 inhibition
Key dose	40 mg once daily, measured as valbenazine free-base equivalent
Product most directly implicated	Ingrezza capsules

Ingrezza was approved by the FDA on April 11, 2017, for the treatment of tardive dyskinesia. The NDA covers valbenazine capsules in 40 mg, 60 mg and 80 mg strengths. The label states that the recommended dosage is 40 mg once daily when Ingrezza is coadministered with a strong CYP2D6 inhibitor. [2]

What does US Patent 11,040,029 claim?

The patent has three principal independent claim concepts.

Claim 1: direct administration of 40 mg with a strong CYP2D6 inhibitor

Claim 1 covers:

1. A patient with tardive dyskinesia;
2. Administration of a strong CYP2D6 inhibitor;
3. Oral, once-daily administration of valbenazine or a pharmaceutically acceptable salt;
4. A dose equivalent to approximately 40 mg of valbenazine.

This is the core claim. It is a method-of-treatment claim rather than a composition claim. The claim does not require a specific brand, capsule strength, duration of therapy or particular CYP2D6 inhibitor. The dependent claims narrow the inhibitor, dosage form, salt form, monitoring activity and pharmacokinetic effect.

The phrase "amount equivalent to about 40 mg" is important. It is designed to cover a salt dose that contains the same amount of active valbenazine free base. A valbenazine ditosylate capsule may therefore infringe even though the total mass of the salt is higher than 40 mg.

Claim 15: reduction from a higher dose after identifying the interaction

Claim 15 covers a treatment sequence:

1. Administering a therapeutically effective amount of valbenazine;
2. Subsequently determining that the patient is receiving a strong CYP2D6 inhibitor;
3. Reducing valbenazine to approximately 40 mg once daily.

Claims 16 and 17 specify that the initial dose may have been approximately 60 mg or 80 mg once daily. This claim set is directed to clinical dose management rather than initial prescribing alone.

The "subsequently determining" limitation narrows the claim. A generic product label that instructs prescribers to begin at 40 mg in all patients receiving a strong CYP2D6 inhibitor may implicate claim 1 more directly than claim 15, which requires the sequence of an earlier higher dose followed by discovery or determination of the inhibitor.

Claim 26: maintaining 40 mg after identifying the inhibitor

Claim 26 covers:

1. Administration of valbenazine ditosylate;
2. An initial dose equivalent to approximately 40 mg once daily;
3. Subsequent determination that the patient has received a strong CYP2D6 inhibitor;
4. Continued administration of the same 40 mg dose.

Claim 26 differs from claim 15 because it does not require a dose reduction. It covers continuation of the 40 mg regimen after the interaction is identified. It also specifically requires the ditosylate salt.

How do the dependent claims narrow the patent scope?

Claims	Limitation
2	Strong CYP2D6 inhibitor selected from bupropion, fluoxetine, metoclopramide, paroxetine, terbinafine, duloxetine, sertraline and quinidine
3	Paroxetine, fluoxetine or quinidine
4	Paroxetine
5	Capsule administration
6-9	Monitoring for exposure-related adverse reactions, including QT prolongation
10-12	Pharmaceutically acceptable salt, ditosylate salt and polymorphic Form I
13-14	Increased exposure of (+)-alpha-HTBZ measured by Cmax or AUC0-inf
16-17	Initial 60 mg or 80 mg once-daily dose before reduction
18-19	Paroxetine, fluoxetine or quinidine, and paroxetine
20	Capsule administration
21-23	Monitoring, particularly somnolence and QT prolongation
24	Valbenazine ditosylate
25	Increased (+)-alpha-HTBZ exposure
26	Continued 40 mg ditosylate regimen after identifying inhibitor use

Claims 2 and 3 are not cumulative exclusions. Claim 3 is a narrower subset of claim 2, and claim 4 narrows claim 3 to paroxetine. The strongest practical claims may be claims 1, 3, 4, 15, 19, 24 and 26, depending on the accused product label and prescribing conduct.

What pharmacology does the patent protect?

Valbenazine is metabolized in part through CYP2D6. Strong CYP2D6 inhibition can increase exposure to valbenazine and its active metabolite, (+)-alpha-HTBZ. The patent links that pharmacokinetic increase to exposure-related safety risks, including somnolence and QT prolongation.

The claims protect the clinical response to that interaction:

• limiting valbenazine to 40 mg once daily;
• reducing a prior 60 mg or 80 mg regimen to 40 mg;
• maintaining 40 mg after identifying concomitant inhibitor use;
• monitoring for adverse reactions;
• recognizing increased active-metabolite exposure by Cmax or AUC.

The claims do not require a particular measured increase in Cmax or AUC unless claim 14 or claim 25 is asserted. Claims 1 and 15 are broader because they require coadministration and dosing but do not impose a numeric pharmacokinetic threshold.

What is the patent's likely claim construction?

"Strong CYP2D6 inhibitor"

The claims expressly identify several inhibitors. Claims 3, 4, 18 and 19 provide narrower species claims for fluoxetine, paroxetine and quinidine. A dispute could arise over whether the term includes only the listed drugs or also other drugs recognized by FDA or clinical pharmacology authorities as strong CYP2D6 inhibitors.

The listed drugs are not uniform in regulatory relevance. Paroxetine, fluoxetine and quinidine are the clearest targets for the narrower claims. Bupropion, duloxetine, sertraline, terbinafine and metoclopramide broaden claim 2's coverage but may create factual disputes concerning classification and dose-dependent inhibition.

"About 40 mg"

"About" creates numerical scope beyond exactly 40 mg, but the claims are anchored to an equivalent amount of valbenazine free base. The term is likely to be construed in view of:

• FDA-approved 40 mg dosing;
• the 40 mg capsule strength;
• the salt-to-free-base conversion;
• the patent specification's examples and analytical methods;
• ordinary pharmaceutical dosing tolerances.

A product labeled only as 40 mg valbenazine equivalent presents a stronger infringement case than a materially different dose that produces comparable exposure.

"Determining that the patient is being administered"

Claims 15 and 26 require a clinical or treatment-management determination. The determination may be made through medication reconciliation, patient history, prescription records or other clinical review. The claim does not appear to require laboratory confirmation.

This limitation creates a possible enforcement issue if the generic label merely describes the interaction but does not instruct a prescriber to perform the claimed sequence.

"Monitoring"

Monitoring is required only in claims 6-9 and 21-23. A claim 1 or claim 15 infringement case does not necessarily require proof that the patient was monitored. Monitoring claims may be useful as fallback claims if the label expressly instructs clinicians to monitor for somnolence or QT prolongation.

What formulations are protected by US 11,040,029?

The patent has formulation limitations but is not principally a formulation patent.

Covered formulations

The claims reach:

• oral valbenazine;
• pharmaceutically acceptable valbenazine salts;
• valbenazine ditosylate;
• ditosylate polymorphic Form I;
• capsule dosage forms.

Claim 12 is the most specific solid-form claim because it requires ditosylate Form I. Claims 11 and 24 require the ditosylate salt but do not both require Form I.

What the patent does not claim

The patent does not expressly claim:

• a particular capsule shell;
• excipient composition;
• dissolution profile;
• particle-size distribution;
• manufacturing process;
• tablet dosage form as such;
• injectable valbenazine;
• a specific commercial package;
• a specific release profile.

A generic capsule using a different excipient system may still fall within the method claims if it administers the claimed valbenazine amount and follows the covered CYP2D6 dosing regimen.

What is the Orange Book status of US Patent 11,040,029?

US Patent 11,040,029 is a drug-use patent associated with valbenazine and Ingrezza. Its commercial significance arises from listing against the NDA and the resulting obligation for an ANDA applicant to address the listed patent through a Paragraph IV certification, a section viii statement or a later certification based on the patent's status. [1][3]

The patent is not a product-by-process or manufacturing patent. Its Orange Book relevance is based on methods of using valbenazine for tardive dyskinesia in a specified drug-interaction setting.

Regulatory issue	Effect
NDA product	Ingrezza
NDA holder	Neurocrine Biosciences, Inc.
FDA approval	April 11, 2017
Patent type	Method of treatment and dose-management patent
Key listed use	Valbenazine treatment with strong CYP2D6 inhibition
Likely ANDA issue	Paragraph IV or section viii certification
Generic risk	Label-induced infringement and potential physician-directed use
Biosimilar pathway	Not applicable; valbenazine is a small molecule

The exact Orange Book expiration entry, including any patent-term adjustment, must be distinguished from the nominal 20-year term calculated from the earliest effective nonprovisional filing. The patent's enforceable term is the term recorded by the USPTO and reflected in the Orange Book, not simply the issue date plus 20 years. [1][3]

When does US Patent 11,040,029 lose exclusivity?

The patent is expected to remain commercially relevant through the mid-2030s based on its filing and priority history. Its expiration is separate from:

• FDA five-year or three-year regulatory exclusivity;
• orphan-drug exclusivity;
• pediatric exclusivity;
• other valbenazine composition patents;
• later continuation patents.

The patent does not create a new chemical-entity exclusivity period. Ingrezza's principal regulatory exclusivity has already run or is no longer the primary barrier. The patent's value is its later-expiring method claim coverage.

A generic applicant may receive FDA approval before the patent expiration if it uses a non-infringing label, obtains a favorable Paragraph IV outcome, prevails in litigation, or relies on a settlement date. Approval and commercial launch are separate events.

Which companies are challenging the Ingrezza patent estate?

Generic competition is likely to arise through ANDA applicants rather than biosimilar applicants. Public litigation and Orange Book certification activity should be evaluated patent by patent because an ANDA applicant may challenge the composition, solid-form, method-of-use and formulation patents in separate proceedings.

Potential challenge categories include:

1. Paragraph IV invalidity challenges based on obviousness, anticipation, lack of written description or indefiniteness;
2. Non-infringement positions based on omission of the protected CYP2D6-use language;
3. Section viii carve-outs removing the patented interaction-related indication or dosing instruction;
4. Challenges to the salt or polymorph claims;
5. Declaratory judgment actions concerning patent listing or scope.

A company could avoid direct infringement of a method claim by omitting the relevant indication from its label. That strategy is less effective when the remaining label still instructs doctors to administer 40 mg with a strong CYP2D6 inhibitor, or when the patented use is inseparable from the approved dosing instructions.

No biosimilar pathway applies. Valbenazine is a chemically synthesized small molecule, so competition would proceed through the ANDA pathway rather than the Biologics Price Competition and Innovation Act pathway.

What Paragraph IV risks apply to generic valbenazine?

Induced infringement risk

The principal risk is induced infringement under 35 U.S.C. § 271(b). A generic label can support an induced-infringement claim if it encourages physicians to use valbenazine in the patented manner. The risk is strongest where the label states:

• use for tardive dyskinesia;
• coadministration with strong CYP2D6 inhibitors;
• a 40 mg once-daily maximum or recommended dose;
• specific monitoring for QT prolongation or somnolence.

The label need not reproduce the patent claims verbatim. Courts examine the label's instructions and whether the proposed use is an intended use of the generic product.

Direct infringement

Direct method infringement ordinarily requires performance of each claimed step. For claims 1-14, the relevant actor may be the physician, patient or a combination of treatment participants. For claims 15 and 26, the actor must also perform the determination and dose-management steps.

Divided-infringement issues are therefore material. If one person prescribes, another dispenses, and the patient takes the drug, the patentee may need to establish direction or control, joint performance or another viable infringement theory.

Section viii strategy

A section viii carve-out may reduce risk if the generic label excludes the patented use. It may be difficult to implement if the 40 mg CYP2D6 adjustment is embedded in the general dosage-and-administration section needed for safe use of the product.

Claims 4 and 19 create a narrower risk around paroxetine. A generic applicant may attempt to omit specific inhibitor examples while retaining a general interaction warning. Whether that avoids infringement would depend on the final label language and claim construction.

How strong is the patent estate for this use?

The patent is strongest as a targeted lifecycle-management patent and weaker as a barrier to all generic valbenazine sales.

Strength factor	Assessment
Commercial alignment	Strong; the claims track an FDA-recognized dose adjustment
Claim specificity	Moderate to strong; dose, interaction and disease are defined
Composition coverage	Weak; the patent does not broadly claim valbenazine
Formulation coverage	Limited; capsule and salt limitations are present
Label-infringement leverage	Moderate to strong
Clinical-practice enforcement	Fact-intensive
Obviousness exposure	Material because CYP2D6 interaction data and dose adjustment may be argued as predictable
Solid-form claim value	Potentially strong against an identical ditosylate Form I
Manufacturing protection	Minimal
Biosimilar relevance	None

Potential validity challenges

A Paragraph IV challenger could argue that the claimed dose adjustment was obvious from:

• known CYP2D6 metabolism;
• prior pharmacokinetic studies;
• known effects of strong CYP2D6 inhibitors;
• FDA dose-adjustment principles;
• prior art involving tetrabenazine analogues or VMAT2 inhibitors.

The patentee would likely rely on the specific clinical consequences of the interaction, the selected 40 mg dose, increased (+)-alpha-HTBZ exposure, and the safety-monitoring framework.

Claims 13-14 and 25 may have a narrower but potentially more defensible evidentiary basis because they recite a pharmacokinetic relationship. Claims 6-9 and 21-23 may face written-description or obviousness arguments if the monitoring list is viewed as a predictable safety response to increased exposure.

How does this patent compare with core valbenazine patents?

Patent category	Scope	Generic barrier
Core composition patent	Valbenazine molecule and related analogues	Broadest chemical protection
Salt patent	Valbenazine ditosylate	Protects the commercial API form
Polymorph patent	Dit osylate Form I or other crystalline forms	Can block use of the same solid form
Formulation patent	Capsule composition, dissolution or stability	Product-specific protection
US 11,040,029	CYP2D6 coadministration and 40 mg dosing	Use-specific, label-dependent protection
Method-of-use patent	Tardive dyskinesia treatment	Depends on indication and prescribing instructions

US 11,040,029 should therefore be analyzed as one layer of the Ingrezza estate. A generic applicant that defeats this patent may still face composition, salt, polymorph, formulation or other method-of-use patents.

What litigation and settlement issues affect generic launch timing?

A Paragraph IV notice can trigger a 30-month FDA approval stay under Hatch-Waxman if the NDA holder timely files an infringement action. The stay does not automatically prohibit all settlement activity, and the ultimate launch date may be determined by:

• patent expiration;
• a court judgment;
• a license;
• a settlement with an agreed entry date;
• an authorized generic arrangement;
• pediatric or other term extensions;
• regulatory approval timing.

Settlement agreements involving delayed generic entry may be subject to Federal Trade Commission review and filing requirements under the Medicare Modernization Act. [4] A settlement can preserve the patent's commercial value even if the claims face validity risk, while an at-risk launch exposes the generic to damages and injunctive relief.

What revenue exposure does the patent protect?

The patent protects a narrow but clinically important segment of Ingrezza use: patients with tardive dyskinesia who require a strong CYP2D6 inhibitor and therefore receive the 40 mg regimen or a dose reduction to 40 mg.

The patent does not cover:

• all Ingrezza prescriptions;
• patients receiving 60 mg or 80 mg without a strong CYP2D6 inhibitor;
• all VMAT2 inhibitor therapy;
• deutetrabenazine or Austedo;
• valbenazine manufacturing;
• non-tardive-dyskinesia uses unless separately claimed.

Its revenue exposure is therefore a subset of total Ingrezza sales. Its strategic value may exceed that subset because the patented instruction is integrated into the product's FDA-approved dosing information. A successful label-based enforcement action could delay generic substitution across the broader product market even if the patent technically covers only a defined interaction scenario.

What generic launch scenarios exist for valbenazine?

Scenario 1: Launch after patent expiration

This is the lowest litigation-risk route. The generic retains the full approved indication and interaction dosing language but waits until the enforceable patent term ends.

Scenario 2: Paragraph IV challenge

The applicant alleges that US 11,040,029 is invalid, unenforceable or not infringed. A successful challenge can support earlier approval or launch. Litigation may also involve other listed Ingrezza patents.

Scenario 3: Section viii carve-out

The applicant removes the patented use or dosing instruction from the label. This route depends on whether the FDA accepts the carve-out and whether the remaining label still encourages the patented use.

Scenario 4: Settlement or license

The applicant receives a negotiated launch date or license. Commercial terms may include delayed entry, royalties, authorized generic rights or restrictions on the label.

Scenario 5: At-risk launch

The generic launches before final resolution. This creates potential exposure to damages, an injunction and loss of market access if Neurocrine prevails.

Key Takeaways

• US Patent 11,040,029 is a method-of-treatment patent for valbenazine in patients receiving strong CYP2D6 inhibitors.
• The central protected regimen is approximately 40 mg of valbenazine once daily.
• Claims 15 and 26 separately cover dose reduction from 60 mg or 80 mg and continuation of 40 mg after the interaction is identified.
• Valbenazine ditosylate and ditosylate Form I are covered by dependent claims.
• The patent does not broadly protect the valbenazine molecule, capsule formulation or manufacturing process.
• The principal generic threat is a Paragraph IV challenge combined with a section viii label carve-out.
• Induced infringement risk is substantial if a generic label repeats the FDA-approved 40 mg CYP2D6 dosing instruction.
• No biosimilar pathway applies because valbenazine is a small-molecule drug.
• The patent should be assessed together with the broader Ingrezza composition, salt, polymorph, formulation and method-of-use estate.
• Commercial exclusivity extends into the mid-2030s based on the patent family's filing history, subject to the enforceable term recorded for the patent.

FAQs

Does US Patent 11,040,029 cover Ingrezza 80 mg?

No. It covers administration of approximately 40 mg once daily when a strong CYP2D6 inhibitor is present and covers reduction from an 80 mg regimen to 40 mg. It does not broadly prohibit 80 mg use in patients who are not receiving a strong CYP2D6 inhibitor.

Does the patent cover valbenazine used for Huntington's disease?

No. The claims are directed to ameliorating symptoms of tardive dyskinesia. They do not claim Huntington's disease treatment.

Can a generic valbenazine product avoid this patent by using tablets instead of capsules?

Possibly, but changing the dosage form alone may not avoid the independent claims. Capsule limitations appear in dependent claims, while claims 1, 15 and 26 generally require oral administration without requiring a capsule.

Does the patent cover paroxetine coadministration specifically?

Yes. Claims 4 and 19 specifically identify paroxetine. Claims 3 and 18 also cover paroxetine as one member of a narrower inhibitor group.

Is polymorphic Form I required for every claim?

No. Form I is required only by claim 12. Other claims cover valbenazine generally, pharmaceutically acceptable salts, or the ditosylate salt without requiring Form I.

References

1. United States Patent and Trademark Office. (2021). U.S. Patent No. 11,040,029, methods of treating tardive dyskinesia.
2. U.S. Food and Drug Administration. (2024). Ingrezza (valbenazine) prescribing information. Neurocrine Biosciences, Inc.
3. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book.
4. Federal Trade Commission. (2024). Agreements filed with the Federal Trade Commission under the Medicare Prescription Drug, Improvement, and Modernization Act of 2003.

Drugs Protected by US Patent 11,040,029

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Neurocrine	INGREZZA	valbenazine tosylate	CAPSULE;ORAL	209241-001	Apr 11, 2017	AB	RX	Yes	No						TREATMENT OF TARDIVE DYSKINESIA
Neurocrine	INGREZZA	valbenazine tosylate	CAPSULE;ORAL	209241-003	Apr 23, 2021		RX	Yes	No						TREATMENT OF TARDIVE DYSKINESIA
Neurocrine	INGREZZA	valbenazine tosylate	CAPSULE;ORAL	209241-002	Oct 4, 2017	AB	RX	Yes	Yes						TREATMENT OF TARDIVE DYSKINESIA
Neurocrine	INGREZZA SPRINKLE	valbenazine tosylate	CAPSULE;ORAL	218390-001	Apr 30, 2024		RX	Yes	No						TREATMENT OF TARDIVE DYSKINESIA

International Family Members for US Patent 11,040,029

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2017395700
Australia	2017395701
Australia	2017395702
Australia	2017395703