Details for Patent: 10,919,892

Which drugs does patent 10,919,892 protect, and when does it expire?

Patent 10,919,892 protects INGREZZA and INGREZZA SPRINKLE and is included in two NDAs.

This patent has twenty-one patent family members in sixteen countries.

Summary for Patent: 10,919,892

Title:	Synthetic methods for preparation of (S)-(2R,3R,11bR)-3-isobutyl-9,10-dimethoxy-2,3,4,6,7,11b-hexahydro-1H-pyrido[2,1-a]isoquinolin-2-yl 2-amino-3-methylbutanoate di(4-methylbenzenesulfonate)
Abstract:	Provided herein are processes for the preparation of (S)-(2R,3R,11bR)-3-isobutyl-9,10-dimethoxy-2,3,4,6,7,11b-hexahydro-1H-pyrido[2,1-a]isoquinolin-2-yl 2-amino-3-methylbutanoate di(4-methylbenzenesulfonate), or a solvate, hydrate, or polymorph thereof.
Inventor(s):	Kevin MCGEE, Bin-Feng Li, Shawn Branum
Assignee:	Neurocrine Biosciences Inc
Application Number:	US16/929,696
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 10,919,892
Patent Claim Types: see list of patent claims	Composition; Compound;

US Patent 10,919,892: Valbenazine Impurity, Purity, Formulation and Patent Landscape Analysis

US Patent 10,919,892 protects purified valbenazine ditosylate, the active pharmaceutical ingredient in Ingrezza, when it meets specified impurity and moisture limits. Its principal commercial value is manufacturing-related: a generic applicant may need to demonstrate that its valbenazine API falls outside the claimed purity or loss-on-drying ranges, or challenge the patent under Paragraph IV. The patent does not broadly claim valbenazine, all VMAT2 inhibitors, a therapeutic indication, or a manufacturing process.

What compound does US Patent 10,919,892 protect?

The claimed compound is valbenazine ditosylate, also called valbenazine tosylate or valbenazine ditosylate. It is the di-4-methylbenzenesulfonate salt of the stereochemically defined valbenazine molecule.

Valbenazine is a vesicular monoamine transporter 2, or VMAT2, inhibitor marketed by Neurocrine Biosciences as Ingrezza. The FDA approved Ingrezza in April 2017 for tardive dyskinesia and later approved it for chorea associated with Huntington's disease.[2]

The structural claim requires all of the following:

Claim element	Requirement
Pharmacologic class	VMAT2 inhibitor
Active molecule	The specified valbenazine stereoisomer
Salt form	Di(4-methylbenzenesulfonate), commonly called ditosylate
Chemical purity	Total impurities no greater than about 5% by weight
Additional limitations	Claims 2-14 specify tighter purity thresholds or named impurities
Moisture limitation	Claims 15-24 specify loss on drying, or LOD
Composition limitation	Claims 25-30 require a pharmaceutical composition containing the claimed API

A different valbenazine salt, racemate, stereoisomer, free base, or unrelated VMAT2 inhibitor does not satisfy the compound limitation on the face of these claims.

What are the independent claims in US 10,919,892?

The patent has three operative independent-claim groups:

1. Claim 1 covers valbenazine ditosylate with total impurities of no more than about 5% by weight.
2. Claim 15 covers the same material with LOD of no more than about 5% by weight.
3. Claim 25 covers a pharmaceutical composition containing the claim 1 material and a pharmaceutically acceptable carrier.

Claims 2-14 and 16-24 narrow those categories. Claims 26-30 are composition claims that incorporate selected purity, impurity, or LOD limitations.

The patent therefore operates as a product-quality patent with composition claims. It is not principally a process patent.

How do the purity claims work?

The purity claims use a descending ladder:

Claim	Total impurity limit
1	About 5% or less
2	About 3% or less
3	About 2.5% or less
4	About 2% or less
5	About 1.5% or less
6	About 1% or less
7	About 0.5% or less
8	About 0.1% or less

A batch meeting the 0.1% limitation would ordinarily fall within claims 1 through 8, assuming the other limitations are met. A batch with total impurities of 4% could fall within claim 1 but not claims 2-8.

The use of "about" creates a claim-construction issue. The permitted tolerance depends on the specification, analytical method, measurement precision, and technical meaning of the term in the relevant pharmaceutical context. A small difference around a numerical boundary may require expert evidence.

What impurities are covered by US Patent 10,919,892?

Claims 9-14 identify impurity classes and specific chemical impurities. Claim 9 names three structurally related impurities:

• Valbenazine hydroxy precursor or its salt;
• The alanine ester analogue;
• A stereoisomeric valine ester analogue.

Claim 10 identifies a trimethoxy analogue. Claim 11 identifies 6,7-dimethoxy-3,4-dihydroisoquinoline. Claim 12 identifies an oxidized 7-oxo derivative. Claim 13 covers metal-based impurities. Claim 14 covers residual process chemicals, including dimethylamine, formaldehyde, ethyl chloride, and isopropyl chloride.

Because these claims depend from claim 1, the listed impurity must be present in a valbenazine ditosylate product that also satisfies the inherited total-impurity limitation. The language "comprising" generally indicates that the claim is open-ended. The presence of one listed impurity does not necessarily exclude other impurities.

The claims do not establish a separate numerical limit for each named impurity. Their practical effect is to identify impurity profiles that can distinguish the claimed product from a less purified or differently manufactured valbenazine batch.

Are trace impurities enough to infringe?

Potentially, but presence alone is not enough for most of the dependent claims. The accused material would need to meet the inherited claim 1 limitations, including:

• The specified valbenazine ditosylate identity;
• Total impurities at or below the applicable threshold;
• The claimed named impurity, where required.

Analytical proof would likely involve validated HPLC, LC-MS, GC, ICP-MS or related methods, depending on the impurity. For residual solvents and metals, the testing method and reporting threshold would be central.

What do the loss-on-drying claims protect?

Claims 15-24 cover valbenazine ditosylate with specified LOD limits:

Claim	LOD limit
15	About 5% or less
16	About 4% or less
17	About 3% or less
18	About 2% or less
19	About 1% or less
20	About 0.8% or less
21	About 0.6% or less
22	About 0.4% or less
23	About 0.2% or less
24	About 0.1% or less

LOD is not necessarily equivalent to water content. It may capture water, residual solvents, volatile materials, or other substances lost under the test conditions. A generic manufacturer could therefore face disputes over the precise LOD method, temperature, drying time, sample preparation, and whether the material is a hydrate or solvated form.

A product with LOD of 0.1% or less would ordinarily satisfy the broader LOD claims as well as claim 24. The LOD claims are potentially important because solid-state and drying conditions can vary between manufacturers even when the chemical identity is the same.

What pharmaceutical compositions are protected?

Claims 25-30 cover compositions containing the defined valbenazine ditosylate and a pharmaceutically acceptable carrier.

The composition claims are narrower than a conventional claim covering any dosage form of valbenazine because the API must first satisfy the incorporated quality limitation. The claims can reach tablets, capsules, or other dosage forms if the API and carrier limitations are met. They do not expressly require a particular dose, release profile, excipient, indication, or route of administration.

The claims do not appear to provide a broad formulation monopoly over all Ingrezza products. Their scope turns on the quality attributes of the API incorporated into the composition.

When does US Patent 10,919,892 lose exclusivity?

The patent issued on February 16, 2021.[1] Its nominal patent term is tied to the earliest effective nonprovisional filing or priority date, subject to patent-term adjustment, terminal disclaimers, PTA, PTE, and any applicable statutory adjustments.

Public patent records identify a late-2030s expiration horizon for this valbenazine purity patent. The operative date should be taken from the USPTO Patent Center term information and the current FDA Orange Book listing, rather than calculated solely from the issue date.[3][4]

The patent is separate from FDA regulatory exclusivity:

Exclusivity type	Relevance
Patent exclusivity	Enforced through infringement litigation
New chemical entity exclusivity	Applies independently of the patent term
Orphan-drug exclusivity	May apply to an indication if FDA granted orphan designation
Pediatric exclusivity	Adds six months if statutory requirements are met
Regulatory data exclusivity	Controls reliance on the innovator's FDA application under applicable ANDA rules

Patent expiration does not automatically mean immediate generic marketing if another listed patent or regulatory exclusivity remains in force.

What is the Orange Book status of US 10,919,892?

The relevant Orange Book question is whether U.S. Patent 10,919,892 is listed against NDA 209241 for Ingrezza and which approved uses or dosage forms it covers.[3]

A listed patent can create an ANDA certification obligation. For a patent listed by the NDA holder, an applicant generally must submit one of the following certifications:

• Paragraph I: No patent information has been submitted;
• Paragraph II: The patent has expired;
• Paragraph III: The applicant will wait until patent expiration;
• Paragraph IV: The patent is invalid, unenforceable, or will not be infringed.

The legal impact depends on the Orange Book listing and the ANDA's proposed labeling. A patent directed to a purified API or composition may be challenged even where the ANDA does not copy a specific branded manufacturing process.

What Paragraph IV risks does this patent create?

A Paragraph IV challenge would likely focus on four issues.

Anticipation

The challenger would seek prior art disclosing valbenazine ditosylate with the claimed impurity or LOD profile. A prior-art reference may need to disclose the numerical quality limitation expressly or inherently.

A generic valbenazine reference that identifies only chemical identity may not anticipate a purity-defined claim unless the claimed purity is necessarily present.

Obviousness

The challenger could argue that routine purification, crystallization, drying, solvent exchange, or analytical control would have produced the claimed quality profile. The patent holder would likely rely on unexpected impurity reduction, improved stability, reproducibility, or manufacturing advantages.

Written description and enablement

The claims cover broad numerical ranges and multiple impurity categories. A challenger could argue that the specification does not support the full breadth of every claimed threshold or impurity combination, or does not enable production across the complete scope without undue experimentation.

Indefiniteness

Terms likely to receive scrutiny include:

• "about";
• "total impurities";
• "impurity profile";
• "weight";
• "metal-based impurities";
• "loss on drying."

The analytical method used to determine total impurities and LOD may be decisive. If the patent specification provides a defined method, that method will carry substantial weight in claim construction.

Which companies are challenging Ingrezza patents?

Teva Pharmaceuticals is the primary commercial competitor in the VMAT2 market through Austedo and Austedo XR, but Austedo is deutetrabenazine and is not a generic version of Ingrezza. Generic manufacturers seeking approval for valbenazine would be the more direct Paragraph IV challengers.

A patent challenge could come from an ANDA applicant such as Teva, Dr. Reddy's, Zydus, Sun Pharma, Lupin, Amneal, Torrent, or another generic company. No company should be treated as having challenged this specific patent without confirmation from the FDA ANDA litigation notice, a filed district-court complaint, or a docketed patent case.

The relevant litigation trigger under the Hatch-Waxman framework is generally:

1. ANDA filing with a Paragraph IV certification;
2. Notice to the NDA and patent holders;
3. Patent-holder suit within 45 days;
4. Potential 30-month stay of approval, subject to statutory exceptions and court rulings.

How strong is the patent estate for valbenazine?

US 10,919,892 is strongest against a generic that uses the same active salt and produces a high-purity, low-moisture API. It is weaker against a manufacturer that can demonstrate:

• A different salt or solid form;
• A product outside the claimed impurity range;
• An LOD outside the claimed range;
• A formulation that does not contain the claimed API quality profile;
• Invalidity based on prior art or lack of written description.

The patent's manufacturing relevance increases its value because generic applicants normally must produce pharmaceutical-grade API. At the same time, quality specifications are often inherent or routinely achieved in commercial pharmaceutical manufacturing, creating obviousness and inherent-anticipation arguments.

Patent-estate comparison

Estate category	Commercial target	Relevance to generic entry
Core valbenazine composition patents	Active molecule or salt	Direct
Purity and impurity patents	API quality profile	High for API suppliers
LOD and solid-state patents	Moisture and physical form	High if listed and enforceable
Method-of-use patents	Tardive dyskinesia or Huntington's chorea	Depends on ANDA labeling
Formulation patents	Tablet, capsule, excipient or release profile	Depends on the proposed dosage form
Manufacturing patents	Synthetic route or purification process	Avoidable if the generic uses a different process

Is there biosimilar risk for Ingrezza?

No conventional biosimilar pathway applies. Valbenazine is a small-molecule drug, not a biologic. The relevant pathway is an ANDA under section 505(j) of the Federal Food, Drug, and Cosmetic Act, with patent certifications under Hatch-Waxman.

The competitive risks are therefore:

• Generic valbenazine;
• Paragraph IV litigation;
• At-risk launch after a favorable court ruling;
• Authorized generic competition;
• Therapeutic substitution by deutetrabenazine or tetrabenazine.

What licensing deals affect valbenazine?

Neurocrine Biosciences controls the Ingrezza commercial franchise. Commercial rights, development collaborations, or regional arrangements should be distinguished from ownership of US Patent 10,919,892. A licensee may have commercialization rights without being the patent owner or Orange Book patent holder.

The patent landscape should therefore track three entities separately:

1. Patent owner and assignee;
2. NDA holder;
3. Commercial distributor or regional licensee.

The claims themselves do not disclose a licensing arrangement. Assignment and ownership should be verified through USPTO assignment records.[4]

What generic launch scenarios exist?

Scenario	Likely result
No Paragraph IV filing	Entry generally waits for patent and regulatory barriers to clear
Paragraph IV with settlement	Entry date depends on the settlement terms
Paragraph IV with patent invalidated	Possible launch before nominal expiration, subject to other patents
Patent not infringed	Possible launch if no other barrier applies
At-risk launch	Generic enters before final resolution and assumes damages and injunction risk
Design-around	Generic changes salt, process, moisture profile, or formulation, subject to FDA requirements

A design-around is technically possible but commercially difficult if the approved product requires valbenazine ditosylate and a generic must demonstrate pharmaceutical comparability to the reference product.

What geographic coverage does the patent have?

US Patent 10,919,892 has territorial effect in the United States only. Separate patent families may protect valbenazine, its salts, purity profiles, formulations, uses, or manufacturing methods in Europe, Canada, Japan, China, and other markets.

A US claim directed to impurity levels does not create automatic protection abroad. International risk must be assessed jurisdiction by jurisdiction, including:

• Patent status;
• National-phase scope;
• Supplementary protection certificates;
• Local Orange Book equivalents;
• Generic approval and launch rules;
• Local claim-construction standards.

Key Takeaways

• US 10,919,892 is a valbenazine ditosylate quality patent.
• Its core limitations are total impurity content and loss on drying.
• Claims 9-14 identify specific organic, inorganic, and residual-solvent impurities.
• Claims 25-30 extend selected API-quality limitations to pharmaceutical compositions.
• The patent does not broadly cover all VMAT2 inhibitors, all valbenazine products, or a treatment method.
• Paragraph IV risk will turn on analytical testing, claim construction, prior art, and the Orange Book listing.
• Valbenazine is a small molecule, so generic entry proceeds through ANDA procedures rather than a biosimilar application.
• The late-2030s patent horizon makes this patent potentially relevant to long-term Ingrezza market exclusivity, subject to the official USPTO and FDA term records.
• Generic applicants may pursue invalidity, noninfringement, or process and quality-profile design-arounds.

FAQs About US Patent 10,919,892

Does US 10,919,892 cover Ingrezza?

It can cover Ingrezza if the product contains valbenazine ditosylate meeting the claimed impurity or LOD limitations. Product-specific infringement depends on the marketed API's tested characteristics and the enforceable claim scope.

Is US 10,919,892 a formulation patent?

It includes pharmaceutical composition claims, but its principal limitations are API purity and moisture content. It is not a conventional formulation patent limited to a particular tablet technology or excipient system.

Can a generic avoid US 10,919,892 by using a different manufacturing process?

Not necessarily. A process change alone does not avoid a product claim if the resulting valbenazine ditosylate has the claimed impurity and LOD profile. A different process may help avoid a separate process patent.

Does the patent cover deutetrabenazine or tetrabenazine?

No. The claims are directed to the specified valbenazine ditosylate structure. Deutetrabenazine and tetrabenazine are chemically different VMAT2 inhibitors.

What evidence would be most important in litigation?

The key evidence would include the accused API batch records, validated impurity assays, LOD testing, reference standards, manufacturing specifications, stability data, and the proposed ANDA product and process information.

References

1. United States Patent and Trademark Office. (2021). U.S. Patent No. 10,919,892, valbenazine compositions.
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. United States Patent and Trademark Office. (2024). Patent Center and assignment search records for U.S. Patent No. 10,919,892.

Drugs Protected by US Patent 10,919,892

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			Y	Y
Neurocrine	INGREZZA	valbenazine tosylate	CAPSULE;ORAL	209241-003	Apr 23, 2021		RX	Yes	No			Y	Y
Neurocrine	INGREZZA	valbenazine tosylate	CAPSULE;ORAL	209241-002	Oct 4, 2017	AB	RX	Yes	Yes			Y	Y

International Family Members for US Patent 10,919,892

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Canada	3009169
China	108925135
China	121045173