Details for Patent: 10,857,137

Which drugs does patent 10,857,137 protect, and when does it expire?

Patent 10,857,137 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: 10,857,137

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 a CYP2D6 poor metabolizer.
Inventor(s):	Christopher F. O'Brien, Haig P. Bozigian
Assignee:	Neurocrine Biosciences Inc
Application Number:	US16/870,706
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 10,857,137
Patent Claim Types: see list of patent claims	Use; Dosage form;

United States Patent 10,857,137: Valbenazine CYP2D6 Dosing Claims, Scope and Patent Landscape

US Patent No. 10,857,137 is a Neurocrine Biosciences method-of-treatment patent directed to once-daily valbenazine dosing in patients with tardive dyskinesia who are CYP2D6 poor metabolizers. Its core commercial subject matter is the 40 mg once-daily dose used for patients with increased exposure to valbenazine’s active metabolite. The patent also covers genotype-directed dosing, dose reduction after metabolizer-status determination, adverse-event monitoring, capsule administration, food-independent administration and the ditosylate salt, including polymorphic Form I. [1]

What drug and clinical use does US 10,857,137 protect?

The compound described by the claims is valbenazine, the active pharmaceutical ingredient in Ingrezza. The claims use the chemical name rather than the generic name. Valbenazine is a vesicular monoamine transporter 2, or VMAT2, inhibitor approved by the FDA for tardive dyskinesia and chorea associated with Huntington's disease. [2]

The patent is directed to pharmacogenomic dosing rather than discovery of the VMAT2 inhibitor itself. The protected clinical concept is:

1. Identify or treat a patient with tardive dyskinesia.
2. Determine whether the patient is a CYP2D6 poor metabolizer.
3. Administer valbenazine orally once daily.
4. Use approximately 40 mg valbenazine equivalent in the poor-metabolizer population.
5. In some claims, monitor exposure-related adverse reactions or adjust the dose after testing.

The claims therefore connect three elements:

• The disease: tardive dyskinesia.
• The patient characteristic: CYP2D6 poor-metabolizer status or genotype.
• The regimen: valbenazine at a specified once-daily dose, principally 40 mg.

How many independent claims does US 10,857,137 contain?

The provided claim set contains three independent method claims: claims 1, 17 and 27. Claim 30 is also drafted as an independent method claim, although it substantially overlaps claim 17.

Claim	Independent subject matter	Principal limitation
1	Treating a CYP2D6 poor metabolizer with tardive dyskinesia	Valbenazine, orally, once daily, about 40 mg equivalent
17	Treating first, then determining poor-metabolizer status and reducing dose	Initial treatment followed by dose reduction to about 40 mg once daily
27	Testing before selecting the treatment regimen	40 mg once daily for poor metabolizers; 40 mg for one week followed by escalation for non-poor metabolizers
30	Treating at 40 mg, then confirming poor-metabolizer status	Same 40 mg dose continued after confirmation

Claims 2 through 16 depend from claim 1. Claims 18 through 26 depend principally from claim 17. Claims 28 and 29 depend from claim 27. Claim 30 is independently framed.

What is the scope of claim 1?

Claim 1 is the principal narrow regimen claim. A practicing party would need to satisfy all of the following limitations:

• The patient has tardive dyskinesia.
• The patient is a CYP2D6 poor metabolizer.
• The administered agent is valbenazine or a pharmaceutically acceptable salt.
• Administration is oral.
• Administration occurs once daily.
• The dose is approximately 40 mg measured as valbenazine free-base equivalent.

The claim does not require a specific CYP2D6 test, a particular commercial product, a capsule, administration with or without food, or a specific salt. Those limitations appear in dependent claims.

The claim is narrower than a general valbenazine treatment claim. A patient with tardive dyskinesia who is not a CYP2D6 poor metabolizer would not fall within claim 1. A poor metabolizer treated with a different VMAT2 inhibitor also would not fall within claim 1.

The phrase “about 40 mg” creates an ordinary claim-construction issue. The relevant dose is measured by valbenazine equivalent, not necessarily by the total mass of a salt or capsule fill. A 40 mg labeled dose of valbenazine ditosylate would be evaluated according to the amount of valbenazine active moiety.

Which patient genotypes are covered?

Claims 3 through 5 identify two CYP2D6 genetic variants:

• CYP2D6G1846A.
• CYP2D6C100T.

The specific genotypes are:

Claim	Genotype
4	CYP2D6G1846A, AA
5	CYP2D6C100T, TT or CT
20	CYP2D6G1846A, AA
21	CYP2D6C100T, TT or CT

These claims provide narrower fallback positions than the broader “poor metabolizer” language in claims 1, 2, 17 and 27. A challenge to the broader phenotype limitation would not necessarily eliminate the genotype-specific claims if the specification and prosecution history support the listed genotypes.

A practical issue is that modern pharmacogenomic nomenclature often identifies CYP2D6 alleles using star-allele designations rather than only nucleotide substitutions. The enforceable scope will depend on how the patent defines the mutations, genotype, poor-metabolizer phenotype and relevant testing methodology.

What dosing regimens are protected?

The patent covers several different clinical sequences.

40 mg once daily in a known poor metabolizer

Claims 1 and 2 cover direct administration of approximately 40 mg once daily when the patient is already known to be a CYP2D6 poor metabolizer.

Claims 4 and 5 narrow the population to specified CYP2D6 genotypes.

Dose reduction after testing

Claim 17 covers a patient who initially receives a therapeutically effective dose, followed by:

1. Determination that the patient is a CYP2D6 poor metabolizer.
2. Reduction to approximately 40 mg once daily.

Claims 18 and 19 identify initial doses of approximately 60 mg and 80 mg once daily. This creates a dose-adjustment claim covering treatment that begins at a higher dose and is later reduced after metabolizer status is established.

Testing before dose selection

Claim 27 covers testing before treatment selection. For a poor metabolizer, the regimen is approximately 40 mg once daily. For a patient who is not a poor metabolizer, the regimen begins at approximately 40 mg once daily for one week and then increases.

Claim 29 identifies approximately 80 mg once daily as the increased dose.

This claim structure is commercially important because it targets the treatment algorithm, not merely the final dose. A generic or competing product could face risk if its proposed labeling instructs prescribers to genotype or otherwise identify CYP2D6 poor metabolizers and use the claimed regimen.

Continuing 40 mg after confirmation

Claim 30 covers administration of approximately 40 mg once daily, followed by determination that the patient is a CYP2D6 poor metabolizer, with the same dose continued after confirmation. It does not require a reduction from 60 mg or 80 mg.

What formulation and salt forms are protected?

Claims 10 through 14 address product and administration details.

Claim	Limitation
10	Administration with or without food
11	Capsule dosage form
12	Valbenazine tosylate salt
13	Valbenazine ditosylate salt
14	Dit tosylate Form I

The core claims cover valbenazine and pharmaceutically acceptable salts broadly. The salt and polymorph claims provide narrower positions that may be relevant to product-level infringement.

The supplied text contains apparent transcription issues. Claim 24 refers to “(5)-” rather than “(S)-” and uses “pyrido[2,1-c]isoquinolin-2-yl ester,” while the other claims use “pyrido[2,1-a]isoquinolin.” Those differences should be checked against the issued patent PDF and any certificate of correction. If the issued claim contains a genuine chemical-identity discrepancy, it could affect claim construction, validity and enforceability. If it is only a transcription error, the official patent text controls.

What pharmacokinetic relationship does the patent require?

Claims 15, 16, 25 and 26 require increased exposure to valbenazine’s active metabolite in CYP2D6 poor metabolizers compared with non-poor metabolizers receiving the same amount.

Exposure may be measured by:

• Cmax.
• AUC0-∞.

These limitations are useful in prosecution and validity analysis because they tie the dosing regimen to a pharmacokinetic rationale. They also create factual issues in litigation. A plaintiff would need to establish that the accused regimen is used in the claimed patient population and that the relevant active-metabolite exposure relationship is met where required by the asserted claim.

Claims 1 through 14 do not appear to require proof of a measured Cmax or AUC relationship. Claims 15 and 16 do.

What adverse reactions and monitoring activities are covered?

Claims 6 through 9 and 22 through 23 cover monitoring for exposure-related adverse reactions. The listed reactions include:

• Somnolence.
• QT prolongation.
• Anticholinergic effects.
• Balance disorders or falls.
• Headache.
• Akathisia.
• Nausea and vomiting.
• Weight and glucose increases.
• Extrapyramidal symptoms.
• Anxiety and insomnia.
• Prolactin, alkaline phosphatase and bilirubin increases.

Claims 8 and 9 narrow the monitoring limitation to somnolence and QT prolongation, with claim 9 directed solely to QT prolongation. These claims may be difficult to assert against a product based solely on a label unless the label expressly instructs monitoring or the ordinary clinical use includes the claimed monitoring step.

Method-of-treatment infringement generally requires proof that the claimed steps are performed. A product label that instructs clinicians to test CYP2D6 status, select 40 mg for poor metabolizers or monitor QT prolongation can increase induced-infringement exposure.

When does US 10,857,137 lose exclusivity?

US Patent No. 10,857,137 issued on January 5, 2021. The patent term is generally measured from the earliest effective nonprovisional U.S. filing date in its priority chain, subject to patent-term adjustment, terminal disclaimers and any other applicable statutory adjustments. [1]

The claims appear to originate from a 2017-era patent family concerning valbenazine dosing in CYP2D6 poor metabolizers. On that basis, the ordinary expiration point is expected to fall in the 2037 period, subject to the official USPTO term calculation and any terminal disclaimer. The patent’s exact expiration date should be taken from the USPTO patent-term data and the current FDA Orange Book listing, not inferred solely from the issue date.

The FDA label identifies a 40 mg once-daily recommendation for patients who are CYP2D6 poor metabolizers. That regulatory alignment increases the commercial relevance of this patent because the claimed regimen corresponds to labeled use. [2]

What is the Orange Book status of US 10,857,137?

US 10,857,137 is the type of method-of-use patent that can be listed in the Orange Book if it claims an approved method of using Ingrezza and satisfies FDA listing requirements. Orange Book listing should be confirmed against the current product-specific entry for valbenazine and the relevant NDA. [3]

If listed, an ANDA applicant seeking approval for valbenazine could be required to address the patent through:

• Paragraph I certification, if the patent is not listed as relevant.
• Paragraph II certification, if the patent has expired.
• Paragraph III certification, if the applicant will await expiration.
• Paragraph IV certification, asserting that the patent is invalid, unenforceable or not infringed.
• A section viii statement, if the applicant seeks approval with the patented use carved out.

For this patent, a section viii strategy would depend on whether the applicant can omit the CYP2D6 poor-metabolizer dosing instructions while still obtaining approval for non-patented valbenazine uses. That strategy becomes harder if the FDA-approved labeling includes the claimed 40 mg regimen and the generic label would necessarily contain it.

What Paragraph IV risks does the patent create?

A Paragraph IV challenge could attack the patent on several grounds.

Lack of novelty

The challenger would search earlier disclosures of:

• Valbenazine.
• CYP2D6 metabolism.
• Poor-metabolizer pharmacokinetics.
• A 40 mg once-daily regimen.
• Treatment of tardive dyskinesia.
• CYP2D6 genotype-directed dosing.

A reference that discloses each limitation in combination could defeat novelty. A general valbenazine patent or clinical publication that does not disclose CYP2D6 poor-metabolizer dosing would be less damaging to the asserted regimen claims.

Obviousness

Obviousness is the central validity risk. The likely combination would include:

• Prior valbenazine dosing studies.
• Known CYP2D6 metabolism of the active metabolite.
• Pharmacogenomic guidance for CYP2D6 poor metabolizers.
• Known exposure-related risks, including QT prolongation and somnolence.
• Routine dose-reduction practices for patients with impaired metabolism.

The patent holder would respond that the specific 40 mg once-daily regimen, clinical benefit and exposure-risk balance were not predictable and that the prior art did not provide a reasonable expectation of success.

Written description and enablement

The genotype-specific claims may be tested against the specification’s disclosure of the relevant variants, testing methods and linkage between genotype and poor-metabolizer phenotype. The broad salt language could also be tested if the disclosure does not adequately support all pharmaceutically acceptable salts in the claimed clinical regimen.

Indefiniteness and claim construction

Potential issues include:

• The meaning of “about 40 mg.”
• The meaning of “equivalent to” the valbenazine active moiety.
• The scope of “poor metabolizer.”
• Whether “subsequently determining” requires a particular sequence.
• Whether “monitoring” requires active clinical measurement or merely observation.
• The chemical-name inconsistencies in the supplied version of claim 24.

How strong is the patent estate for Ingrezza?

The estate is strongest where the product label directly tracks the claim:

• Tardive dyskinesia.
• CYP2D6 poor-metabolizer population.
• 40 mg once-daily dosing.
• Oral valbenazine.
• Valbenazine ditosylate product.

The estate is weaker for claims requiring individualized clinical conduct, such as monitoring specific adverse events, unless the prescribing information clearly directs that conduct.

US 10,857,137 should be analyzed together with separate valbenazine patent families covering:

• The valbenazine compound.
• Valbenazine salts.
• Solid forms and polymorphs.
• Pharmaceutical compositions.
• Manufacturing processes.
• Additional therapeutic uses.
• Dosing regimens unrelated to CYP2D6 status.

A generic entrant may avoid one family while remaining blocked by another. The commercial launch date therefore depends on the earliest enforceable patent covering the proposed product, label and manufacturing route.

How does the patent compare with deutetrabenazine patents?

Valbenazine and deutetrabenazine are competing VMAT2 inhibitors, but their patent risks differ.

Issue	Valbenazine and US 10,857,137	Deutetrabenazine
Active ingredient	Valbenazine	Deutetrabenazine
Product	Ingrezza	Austedo and Austedo XR
Core patent focus here	CYP2D6 poor-metabolizer dosing	Deuterium-modified VMAT2 inhibitor and dosing
Patient population	Tardive dyskinesia; also relevant to Huntington's disease products	Tardive dyskinesia and Huntington's disease chorea
Key generic risk	Label-based method-of-use claims and compound/formulation patents	Compound, formulation and method-of-use patents
Biosimilar pathway	Not applicable	Not applicable

Both products are small molecules. Biosimilar approval is therefore not the relevant pathway. Competitive entry would proceed through the ANDA pathway for a generic, subject to patent certifications and any litigation stay.

What generic launch scenarios exist?

Three principal scenarios exist:

1. A full-label ANDA challenges the compound, formulation and method-of-use patents through Paragraph IV certifications.
2. A skinny-label ANDA omits CYP2D6 poor-metabolizer dosing and other patented uses, if FDA labeling permits the carve-out.
3. A delayed launch occurs after expiration, settlement, license or successful validity and noninfringement litigation.

A generic that supplies valbenazine ditosylate in a capsule and markets a label containing 40 mg once-daily dosing for CYP2D6 poor metabolizers would face the highest direct risk under this patent.

What licensing, settlement and litigation issues affect the patent?

The supplied patent information does not establish a license, Paragraph IV notice, ANDA litigation event or settlement agreement involving US 10,857,137. Those matters must be verified through the FDA Orange Book, PACER, district-court dockets, USPTO assignment records and SEC filings.

The relevant litigation triggers would be:

• A Paragraph IV notice concerning the patent.
• A patent-infringement complaint filed within 45 days of notice.
• A 30-month ANDA approval stay.
• A settlement permitting an agreed generic entry date.
• A covenant not to sue or license covering the CYP2D6 dosing claims.

Key Takeaways

• US 10,857,137 protects valbenazine treatment of tardive dyskinesia in CYP2D6 poor metabolizers.
• The commercial core is approximately 40 mg once daily, measured as valbenazine equivalent.
• Claims cover direct dosing, post-treatment genotype determination, dose reduction and pre-treatment pharmacogenomic selection.
• CYP2D6G1846A and CYP2D6C100T genotype-specific claims provide narrower fallback positions.
• Valbenazine ditosylate, capsule administration, food-independent dosing and Form I are separately addressed.
• The patent is a method-of-use patent, not the foundational valbenazine composition patent.
• The expected statutory term reaches the 2037 period, subject to the official USPTO term calculation.
• Generic risk is highest for a full-label ANDA that includes the CYP2D6 poor-metabolizer dosing instructions.
• Biosimilar risk does not apply because valbenazine is a small-molecule drug.
• Claim 24 should be checked against the issued patent because the supplied text contains apparent stereochemical and ring-system transcription errors.

FAQs About US Patent 10,857,137

Does US 10,857,137 cover all Ingrezza prescriptions?

No. It principally covers prescriptions for tardive dyskinesia patients who are CYP2D6 poor metabolizers and receive the specified dosing regimen.

Does the patent cover CYP2D6 intermediate metabolizers?

The provided claims expressly identify poor metabolizers. They do not expressly recite intermediate metabolizers. Coverage would depend on the applicable claim construction and whether the patient meets the claimed poor-metabolizer limitation.

Can a generic avoid this patent by using a different salt?

Not necessarily. Claims 1 and 17 broadly cover valbenazine and pharmaceutically acceptable salts. A different salt could avoid a salt-specific dependent claim but may remain within the broader independent claims.

Is a CYP2D6 genetic test required to infringe?

Not for every claim. Claims 1 and 2 require poor-metabolizer status, while claims 3 through 5 and 20 through 21 specify genotypes. Claim 27 expressly requires determining metabolizer status before selecting the regimen.

Does US 10,857,137 cover Huntington's disease chorea?

The provided claims recite treatment of tardive dyskinesia. They do not expressly recite Huntington's disease chorea. Coverage of that indication would require separate claim language in another patent or an applicable construction of the claims.

References

1. United States Patent and Trademark Office. (2021). U.S. Patent No. 10,857,137, Methods of treating tardive dyskinesia.
2. U.S. Food and Drug Administration. (2024). Ingrezza (valbenazine) prescribing information.
3. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book.
4. U.S. Food and Drug Administration. (2024). Abbreviated new drug application regulations and patent certifications.
5. United States Code. (2024). 35 U.S.C. §§ 154, 271(e), and 282.

Drugs Protected by US Patent 10,857,137

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	10,857,137					TREATMENT OF TARDIVE DYSKINESIA
Neurocrine	INGREZZA	valbenazine tosylate	CAPSULE;ORAL	209241-003	Apr 23, 2021		RX	Yes	No	10,857,137					TREATMENT OF TARDIVE DYSKINESIA
Neurocrine	INGREZZA	valbenazine tosylate	CAPSULE;ORAL	209241-002	Oct 4, 2017	AB	RX	Yes	Yes	10,857,137					TREATMENT OF TARDIVE DYSKINESIA
Neurocrine	INGREZZA SPRINKLE	valbenazine tosylate	CAPSULE;ORAL	218390-001	Apr 30, 2024		RX	Yes	No	10,857,137					TREATMENT OF TARDIVE DYSKINESIA
Neurocrine	INGREZZA SPRINKLE	valbenazine tosylate	CAPSULE;ORAL	218390-002	Apr 30, 2024		RX	Yes	No	10,857,137					TREATMENT OF TARDIVE DYSKINESIA

International Family Members for US Patent 10,857,137

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2017395700
Australia	2017395701
Australia	2017395702
Australia	2017395703
Australia	2017395704