US Patent 10,844,058: Valbenazine Tosylate Crystal Form Claims, Exclusivity, and Patent Landscape
US Patent No. 10,844,058 protects a specific crystalline form of valbenazine tosylate, the active pharmaceutical ingredient in Ingrezza. Its core coverage is a solid-state form identified by a differential scanning calorimetry peak near 243°C, with dependent claims adding XRPD peaks, particle-size attributes, purity, stability, pharmaceutical compositions, oral capsules, and treatment of hyperkinetic movement disorders including tardive dyskinesia.
The patent is narrower than a compound patent covering valbenazine generally. Its commercial importance is that a generic product using the claimed valbenazine tosylate crystal form could face infringement risk even if the generic applicant avoids broader compound or method-of-use claims.
What drug and active ingredient does US 10,844,058 protect?
US 10,844,058 covers a crystalline tosylate salt of valbenazine. Valbenazine is the active ingredient marketed by Neurocrine Biosciences as Ingrezza.
The chemical name in claim 1 identifies the valine ester of a tetrabenazine-related benzoquinolizine compound. The protected material is not merely valbenazine in any physical state. It is a particular solid-state form of valbenazine tosylate.
The patent therefore sits within the solid-form segment of the valbenazine patent estate:
| Attribute |
Protected subject matter |
| Active ingredient |
Valbenazine |
| Salt |
Tosylate salt |
| Solid state |
Crystalline form |
| Primary analytical marker |
DSC peak near 243°C |
| Additional identifiers |
XRPD peaks at 6.3°, 17.9°, and 19.7° 2θ |
| Product attributes |
Stability, particle size, purity |
| Dosage forms |
Pharmaceutical compositions, oral unit doses, capsules |
| Medical use |
Hyperkinetic movement disorders, including tardive dyskinesia |
The patent does not, on the supplied claims, cover every polymorph, amorphous form, solvate, hydrate, salt, or free-base form of valbenazine.
What are the independent claims in US 10,844,058?
The patent has three principal claim groups.
Claim 1: crystalline valbenazine tosylate
Claim 1 covers the crystalline form defined by a DSC peak temperature within 2% of 243°C. Assuming “within 2%” is interpreted as a relative numerical range, the approximate interval is:
| DSC limitation |
Approximate temperature range |
| Claim 1, within 2% of 243°C |
238.14°C to 247.86°C |
| Claim 2, within 1% of 243°C |
240.57°C to 245.43°C |
| Claim 3, within 0.5% of 243°C |
241.785°C to 244.215°C |
Claims 2 and 3 narrow claim 1 by imposing progressively tighter DSC limitations. They do not create independent protection for a different chemical entity.
Claim 14: pharmaceutical composition
Claim 14 covers a pharmaceutical composition containing the crystalline form of claim 1 and a pharmaceutically acceptable carrier.
Claims 15 through 17 narrow that composition to:
- oral administration;
- a unit dosage form; and
- a capsule.
Claim 26: treatment method
Claim 26 covers treating a hyperkinetic movement disorder by administering the crystalline form of claim 1, where treatment means ameliorating one or more symptoms.
Claim 27 narrows the disorder to tardive dyskinesia. The method claims are significant because they can create a separate infringement theory from the product claims, although enforcement against an ANDA filer depends on the proposed label, certification, and applicable Hatch-Waxman procedures.
How do the XRPD and DSC limitations define the protected crystal?
The claims use two standard solid-state characterization techniques.
Differential scanning calorimetry
DSC measures heat flow as a material is heated. A peak near 243°C is used as a thermal signature of the claimed crystal. DSC alone may be vulnerable to testing variability caused by heating rate, sample preparation, instrument calibration, impurities, and decomposition behavior.
The dependent claims narrow the acceptable temperature window:
- Claim 1: ±2%;
- Claim 2: ±1%;
- Claim 3: ±0.5%.
A generic manufacturer would typically compare its isolated valbenazine tosylate against the claimed temperature range using validated analytical methods. A product could fall outside the numerical DSC limitation yet still raise infringement issues under other claims if its XRPD pattern or composition satisfies the relevant limitations.
X-ray powder diffraction
Claims 4 through 6 require individual XRPD peaks at:
- 6.3° ±0.2° 2θ;
- 17.9° ±0.2° 2θ; and
- 19.7° ±0.2° 2θ.
Claim 12 combines all three peaks with a purity limitation of at least 97% by weight. This combination is more technically specific than claim 1 and may be easier to test in a product comparison, provided the patent specification identifies the same crystal form through a complete pattern and the peaks are sufficiently diagnostic.
The supplied claims do not state whether claims 4, 5, and 6 require only the listed peak or the listed peak as part of a broader pattern. As written, each claim appears to require the presence of one specified peak in the crystalline form of claim 1.
What formulation patents are protected by US 10,844,058?
The formulation claims cover compositions containing the claimed crystal, rather than a specific excipient system.
| Claim |
Scope |
| 14 |
Composition containing claim 1 crystal and pharmaceutically acceptable carrier |
| 15 |
Oral formulation |
| 16 |
Unit dosage form |
| 17 |
Capsule |
| 18 |
Composition containing claim 12 crystal |
| 19 |
Oral formulation |
| 20 |
Unit dosage form |
| 21 |
Capsule |
| 22 |
Composition containing claim 13 crystal |
| 23 |
Oral formulation |
| 24 |
Unit dosage form |
| 25 |
Capsule |
These claims are structurally repetitive. They separately protect compositions containing the broader claim 1 form, the claim 12 form with specified XRPD peaks and purity, and the form described in claim 13.
A capsule containing the claimed valbenazine tosylate crystal could implicate claims 14 and 17, or the corresponding claims 18 and 21 if the material satisfies claim 12. The claims do not require a particular capsule shell, excipient, dissolution profile, release profile, or manufacturing process.
What is the significance of claims 7 through 13?
Claims 7 through 13 add commercial and analytical attributes.
| Claims |
Added limitation |
Commercial relevance |
| 7 |
Stability at about 25°C and 60% relative humidity |
Supports storage and handling characteristics |
| 8 |
D90 particle size of about 70 µm |
May affect flow, blending, dissolution, and processing |
| 9 |
D10 particle size of about 10 µm |
Defines the lower particle-size distribution |
| 10 |
At least 97% purity |
Adds a compositional threshold |
| 11 |
At least 98% purity |
Narrower purity requirement |
| 12 |
At least 97% purity plus three XRPD peaks |
Combined solid-form and quality limitation |
| 13 |
Chemical identity or form limitation as supplied |
Scope cannot be fully assessed from the incomplete text |
Claims 8 and 9 address particle-size distribution but use “about,” which introduces potential claim-construction questions. Particle-size measurements depend on the analytical method, dispersion medium, agglomeration control, and whether the result is reported by volume, number, or mass.
The supplied text for claim 13 ends with “is:” and does not include the defining chemical structure or subsequent limitation. The scope of claim 13 and claims 22 through 25 cannot be determined from the provided claim text. The supplied claims also use both “pyrido[2,l-a]” and “pyrido[2,1-a],” which may reflect typographical transcription rather than a substantive chemical distinction.
When does US 10,844,058 expire?
US 10,844,058 is a small-molecule patent, so its ordinary term is generally 20 years from the earliest effective nonprovisional U.S. filing date, subject to patent-term adjustment, terminal disclaimers, and any applicable correction.
The patent was granted in 2020. The grant date does not determine expiration. The relevant date is the earliest effective nonprovisional priority date reflected in the patent’s front-page continuity data and USPTO patent-term records. Solid-form patents of this type commonly provide protection into the mid-2030s when based on a 2016 or 2017 priority chain.
The exact expiration date must be taken from the USPTO patent-term calculation and the Orange Book listing, if the patent is listed for an approved product. Any projection based solely on the grant date would be unreliable.
What is the FDA and Orange Book status of valbenazine?
The FDA approved Ingrezza capsules in 2017 for tardive dyskinesia. The indication was later expanded to chorea associated with Huntington’s disease. Current marketed strengths include 40 mg, 60 mg, and 80 mg capsules, according to the FDA labeling materials.[1]
Valbenazine is a small molecule, not a biologic. Biosimilar procedures under the Biologics Price Competition and Innovation Act do not apply. Any follow-on product would proceed through the abbreviated new drug application pathway if it meets the relevant requirements for therapeutic equivalence.
The Orange Book can list patents associated with an approved drug, including drug-substance, drug-product, and method-of-use patents. A patent’s presence in the Orange Book does not itself establish validity or infringement. It determines, however, whether an ANDA applicant must address the listing through a Paragraph I, II, III, or IV certification.
What Paragraph IV challenges could affect valbenazine generic entry?
A generic applicant seeking approval before all listed patents expire would generally need to address each relevant Orange Book patent. A Paragraph IV certification asserts that the listed patent is invalid, unenforceable, or will not be infringed.
For US 10,844,058, the principal technical defenses would likely focus on:
- whether the proposed product contains the claimed crystalline form;
- whether its DSC peak falls within the claimed range;
- whether its XRPD pattern includes the claimed peaks;
- whether the product satisfies the purity or particle-size limitations;
- whether the proposed label induces infringement of claims 26 or 27; and
- whether the claims are invalid for anticipation, obviousness, written-description failure, enablement, indefiniteness, or lack of claim differentiation.
A generic company could seek to design around the patent by using a different polymorph, an amorphous form, a different salt, a different particle-size distribution, or a manufacturing process that produces a crystal lacking the claimed analytical features. That strategy may be difficult if the commercial product’s performance depends on the patented form or if other valbenazine patents cover the active ingredient or formulation.
A Paragraph IV notice would ordinarily create a 45-day period for the patent owner to file suit, which can trigger a 30-month stay of FDA approval under the Hatch-Waxman framework, subject to statutory exceptions and litigation developments.[2]
What patent litigation and settlement risks affect Ingrezza?
The relevant risk is not limited to US 10,844,058. A generic applicant would evaluate the full valbenazine estate, including:
- compound patents;
- salt and polymorph patents;
- formulation patents;
- manufacturing-process patents;
- method-of-use patents for tardive dyskinesia;
- method-of-use patents for Huntington’s disease chorea; and
- Orange Book-listed patents with unexpired terms.
A settlement could permit a generic launch before the latest patent expiration in exchange for a delayed-entry date, a license, or other agreed terms. The commercial effect would depend on the settlement date, authorized-generic strategy, number of approved ANDAs, and whether the agreement is subject to Federal Trade Commission review under the Medicare Prescription Drug, Improvement, and Modernization Act reporting framework.
No settlement terms can be derived from the claims supplied. The claims establish technical scope, not litigation status.
How strong is the patent estate for valbenazine?
The estate has several characteristics that can support meaningful exclusion:
| Strength factor |
Assessment |
| Product specificity |
High for the claimed crystal, because DSC and XRPD markers identify a defined solid form |
| Breadth |
Moderate to narrow; the patent does not cover all valbenazine forms |
| Detectability |
High; DSC and XRPD testing can identify the claimed form |
| Design-around potential |
Moderate; alternative polymorphs, salts, or amorphous material may avoid the claims |
| Formulation coverage |
Moderate; claims cover capsules and oral dosage forms but not a detailed excipient system |
| Method-of-use coverage |
Potentially meaningful for tardive dyskinesia, subject to label and patent validity |
| Manufacturing coverage |
Limited in the supplied claims; no process claim is provided |
| Biosimilar exposure |
None; valbenazine is a small molecule |
The patent is strongest against a product that uses the same valbenazine tosylate crystal and is sold in an oral capsule. It is weaker against a product that uses a demonstrably different solid form and avoids the method-of-use language.
How does US 10,844,058 compare with a compound patent?
A compound patent generally provides broader protection because it can cover the active molecule regardless of crystal form, particle size, or formulation. US 10,844,058 is narrower but may expire later than an original compound patent because solid-form inventions are often filed after development work identifies a commercially useful form.
| Patent category |
Typical scope |
Relevance to generic |
| Compound patent |
Valbenazine molecule and broad salts or derivatives |
Highest product-level risk |
| Solid-form patent |
Specific polymorph or crystalline salt |
High if generic uses the same form |
| Formulation patent |
Capsule, excipient, release, or dosage design |
Depends on proposed product |
| Method patent |
Treatment of tardive dyskinesia or Huntington’s chorea |
Depends on labeling and use |
| Process patent |
Synthesis, crystallization, or purification |
Depends on manufacturing route |
A design-around of US 10,844,058 does not eliminate risk under the other categories.
What revenue is exposed to valbenazine patent expiry?
Ingrezza is Neurocrine’s principal commercial product. Neurocrine’s annual reports identify Ingrezza as the company’s dominant revenue source, with annual net product sales exceeding $2 billion in recent reporting periods.[3]
The economic exposure to generic entry depends on:
- the number and timing of ANDA approvals;
- whether the first filer receives 180-day exclusivity;
- the scope of any Paragraph IV settlement;
- the number of unexpired patents at launch;
- payer substitution policies;
- authorized-generic participation; and
- the extent to which Huntington’s disease chorea sales grow before entry.
A crystal-form patent can delay substitution when the marketed product uses that form, but it does not guarantee market exclusivity if a competitor can commercialize a non-infringing valbenazine form.
Key Takeaways
- US 10,844,058 is a valbenazine tosylate solid-form patent.
- Claim 1 requires a crystalline form with a DSC peak within 2% of 243°C.
- Dependent claims add tighter DSC ranges, XRPD peaks, stability, particle size, and purity.
- Claims 14 through 25 cover oral unit-dose capsules containing the claimed crystal.
- Claims 26 and 27 cover treatment of hyperkinetic movement disorders, including tardive dyskinesia.
- The patent does not, on the supplied claims, cover every form of valbenazine.
- Valbenazine is a small molecule, so biosimilar litigation is not applicable.
- Generic risk depends on the full Orange Book estate, not this patent alone.
- Claim 13 is incomplete in the supplied text, preventing a complete assessment of claims 22 through 25.
- The principal design-around routes are alternative polymorphs, amorphous material, different salts, and non-infringing formulations.
FAQs About US Patent 10,844,058 and Valbenazine
Does US 10,844,058 cover Ingrezza generally?
No. It covers a defined crystalline form of valbenazine tosylate and products containing that form. It is not, based on the supplied claims, a universal patent on every valbenazine product.
Can a generic use a different valbenazine polymorph?
Potentially. A different polymorph may avoid the patent if it does not satisfy the DSC, XRPD, purity, particle-size, and other limitations. The generic would still need to address other valbenazine patents.
Are the XRPD peaks in claims 4 through 6 cumulative?
As written, claims 4, 5, and 6 each add one specified peak to claim 1. Claim 12 expressly requires all three listed peaks together, along with at least 97% purity.
Does the patent protect injectable valbenazine?
The supplied claims focus on pharmaceutical compositions, oral administration, unit dosage forms, and capsules. They do not expressly recite an injectable formulation.
What is the main litigation issue for a Paragraph IV filer?
The central issue would be whether the proposed generic contains the patented crystalline valbenazine tosylate form. DSC and XRPD testing would likely be central to infringement and validity disputes.
References
-
U.S. Food and Drug Administration. (2023). Ingrezza (valbenazine) prescribing information. FDA.
-
U.S. Food and Drug Administration. (n.d.). ANDA submissions: Paragraph IV certifications and patent litigation under the Hatch-Waxman Act. FDA.
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Neurocrine Biosciences, Inc. (2025). Annual report on Form 10-K for the fiscal year ended December 31, 2024. U.S. Securities and Exchange Commission.
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United States Patent and Trademark Office. (2020). U.S. Patent No. 10,844,058, crystalline form of valbenazine tosylate. USPTO.
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U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations, Orange Book. FDA.
