US Patent 8,921,393: Pimavanserin Patent Scope, Claims, Expiration, and Generic-Litigation Risk

US Patent 8,921,393 protects methods of treating neurodegenerative disease and associated psychosis with pimavanserin, including pimavanserin tartrate and hydrochloride salts. The patent covers Parkinson's disease, Alzheimer's disease and several other disorders, with particular protection for daily or once-daily dosing from 0.001 mg to 50 mg. The patent is a method-of-use right, not a composition-of-matter or formulation patent.

The patent is associated with Acadia Pharmaceuticals' Nuplazid product, whose active ingredient is pimavanserin tartrate. The projected US patent expiration is March 30, 2027, subject to the controlling patent-term calculation and any applicable regulatory extensions.[1][2]

What drug does US Patent 8,921,393 protect?

US 8,921,393 covers pimavanserin, also known as ACP-103. The compound is commonly identified chemically as N-(4-fluorophenyl)-N-[1-(4-isobutoxybenzyl)piperidin-4-ylmethyl]carbamate. Nuplazid contains pimavanserin tartrate.[3]

The claims do not recite the compound's name. They define it through "formula (I)." The patent's claim scope therefore depends on the structural definition of formula (I), including its substituents, stereochemical limitations, and pharmaceutically acceptable salts.

Item	Description
Patent	US 8,921,393 B2
Patent type	Method of treatment
Applicant/assignee	Acadia Pharmaceuticals Inc.
Active compound	Pimavanserin
Commercial product	Nuplazid
FDA dosage form	Oral tablets and capsules, depending on product presentation
Claimed salts	Tartrate and hydrochloride
Primary disease area	Neurodegenerative disease and secondary psychosis
Earliest priority date	March 30, 2007
Projected expiration	March 30, 2027
Regulatory pathway	FDA-approved small-molecule drug; ANDA pathway applies

What are the independent claims in US Patent 8,921,393?

The patent has two substantive independent method claims.

Claim 1 covers administering a therapeutically effective amount of formula (I), or a pharmaceutically acceptable salt, to a patient suffering from a neurodegenerative disease or a symptom of that disease.

Claim 19 separately covers treating psychosis secondary to a neurodegenerative disorder with formula (I) or a pharmaceutically acceptable salt.

The two independent claims have different practical centers of gravity:

Claim	Protected subject matter	Commercial relevance
1	Treatment of a neurodegenerative disease or symptom	Broad disease and symptom claim
19	Treatment of psychosis secondary to a neurodegenerative disorder	Closely aligned with Nuplazid's Parkinson's disease psychosis use

Claim 19 does not require the disease list in claim 11. It requires a neurodegenerative disorder and psychosis secondary to that disorder. That structure can make claim 19 commercially important even when a particular disease is not expressly identified in a dependent claim.

How broad is the scope of claim 1?

Claim 1 is broad in therapeutic language but narrow in chemical identity. A potential infringer must satisfy each material limitation:

A patient must be suffering from a neurodegenerative disease or a symptom of one.
The defendant's product must contain formula (I) or a pharmaceutically acceptable salt.
The compound must be administered.
The amount must be therapeutically effective.

The claim is not limited to Parkinson's disease. It reaches the listed conditions in claim 11 and potentially other neurodegenerative diseases if they fall within the ordinary and legally supported meaning of the claim language.

The claim does not expressly limit:

Route of administration
Tablet, capsule, liquid or other dosage form
Treatment duration
Patient age
Disease severity
Treatment setting
Combination therapy
A particular manufacturing process
A specific release profile
A particular crystalline form

The claim is therefore directed to use of the active pharmaceutical ingredient rather than to a particular finished-product design.

What diseases and symptoms are covered?

Claim 11 identifies the following neurodegenerative diseases:

Parkinson's disease
Huntington's disease
Alzheimer's disease
Spinocerebellar atrophy
Tourette's syndrome
Friedrich's ataxia
Machado-Joseph's disease
Lewy body dementia
Dystonia
Progressive supranuclear palsy
Frontotemporal dementia

Claims 12 and 13 narrow the disease to Parkinson's disease and Alzheimer's disease, respectively. Claims 14 and 15 further require the tartrate salt for those two diseases.

Claims 16 through 18 address psychosis secondary to a neurodegenerative disease. Claim 19 then creates a separate independent route to infringement for treating psychosis secondary to a neurodegenerative disorder.

This claim architecture gives the patent several layers:

Layer	Claim examples	Scope
Broad disease treatment	1	Neurodegenerative disease or symptom
Disease list	11	Eleven specified diseases
Parkinson's disease	12, 14	Parkinson's disease, including tartrate
Alzheimer's disease	13, 15	Alzheimer's disease, including tartrate
Secondary psychosis	16-19	Psychosis linked to neurodegenerative disease
Combination therapy	29-36	Secondary psychosis treatment with additional agents

What dosage and dosing schedules are protected?

Claims 4 through 8 and 22 through 26 specify the amount of formula (I) or its salt:

Claims	Dose range or amount
4, 22	About 0.001 mg to about 50 mg
5, 23	About 1 mg to about 10 mg
6, 24	About 10 mg
7, 25	About 25 mg
8, 26	About 50 mg

Claims 9, 10, 27 and 28 require daily or once-daily administration.

Nuplazid's approved dosage for hallucinations and delusions associated with Parkinson's disease psychosis is 34 mg once daily, generally administered as two 17 mg tablets.[3] The 34 mg regimen falls within the patent's broad 0.001 mg-to-50 mg limitation, but it does not fall within the narrower "about 10 mg," "about 25 mg" or "about 50 mg" claims unless the term "about" is construed broadly enough to cover it.

The broad dose-range claims remain more commercially relevant than the narrower fixed-dose claims because they can capture a product using a dose within the range without using one of the expressly recited fixed amounts.

What salts and formulations are protected?

Claims 2, 3, 20 and 21 identify tartrate and hydrochloride salts. Claims 14, 15, 17 and 18 specifically use the tartrate salt in the Parkinson's disease, Alzheimer's disease and secondary-psychosis subcombinations.

The salt claims protect administration of the relevant salt in the claimed treatment method. They do not, by themselves, establish protection for:

A particular crystal form
Particle size
Tablet coating
Excipient combination
Dissolution profile
Extended-release formulation
Packaging
Manufacturing process

Those subjects generally require separate composition, formulation or process claims. US 8,921,393 is therefore best classified as a therapeutic-use patent rather than a formulation patent.

Does the patent cover combination therapy?

Yes. Claim 29 covers treating psychosis secondary to a neurodegenerative disorder while administering formula (I) with an additional therapeutic agent.

The listed agents include:

Levodopa
Bromocriptine
Pergolide
Pramipexole
Modafinil
Ropinirole
Methylphenidate
Baclofen
Botulinum toxin
Clonazepam
Diazepam
Antipsychotics with dopaminergic receptor antagonism

Claim 35 lists specific antipsychotic agents and classes, including haloperidol, clozapine, olanzapine, risperidone, aripiprazole, ziprasidone, amisulpride, sertindole and pimozide. Claim 36 identifies flupenthixol and sulpiride within broader class limitations.

These claims require more than simultaneous commercial availability of two drugs. The claimed combination must be administered in the covered treatment context. A product label that instructs use with a listed agent can create greater method-of-use exposure than a label that omits the combination.

What is the patent expiration date?

The patent's ordinary term is tied to the earliest effective nonprovisional filing date in its family. Based on the March 30, 2007 priority date and the published patent-family information, the projected expiration is March 30, 2027.[1]

Event	Date or status
Earliest priority	March 30, 2007
US patent grant	December 30, 2014
Projected ordinary expiration	March 30, 2027
Patent type	Method of use
Pediatric extension	No separate extension is assumed in the date above
Regulatory exclusivity	Separate from patent term

Patent expiration does not necessarily eliminate every exclusivity barrier. Other listed Nuplazid patents, regulatory exclusivity, litigation settlements and later-issued patents must be analyzed separately.

What is the Orange Book status of US 8,921,393?

US 8,921,393 has been associated with the Orange Book patent estate for Nuplazid and its pimavanserin use. Orange Book listing generally gives an ANDA applicant the choice of submitting a Paragraph IV certification if the applicant asserts that the patent is invalid, unenforceable or will not be infringed.[4]

The listing does not mean that every claim covers every pimavanserin product. The relevant question is whether the proposed ANDA labeling induces use for a patented indication, dose, population or combination.

For a generic applicant, the principal Orange Book issues are:

Whether the patent remains listed on the ANDA submission date
Whether the proposed label includes Parkinson's disease psychosis or another covered use
Whether a section viii statement can carve out the patented indication
Whether the patent is asserted in district court
Whether a settlement limits the generic launch date
Whether later patents create a separate launch barrier

Which companies challenged Nuplazid patents?

Acadia's Nuplazid patent estate has been challenged through ANDA litigation by multiple generic drug companies, including Teva and other manufacturers that filed or pursued abbreviated applications for pimavanserin products. These disputes have involved later-issued patents as well as the earlier method-of-use estate.

The commercial effect of a Paragraph IV challenge is not determined solely by US 8,921,393. A generic applicant must assess the complete Orange Book listing, including patents covering the active ingredient, approved uses, crystalline or salt forms, formulations and manufacturing methods.

The principal litigation risks are:

Risk	Effect on generic launch
Paragraph IV notice	Can trigger patent litigation
30-month stay	May delay FDA approval while litigation proceeds
Successful noninfringement position	Can permit approval after regulatory conditions are met
Successful invalidity challenge	Removes the asserted patent barrier
Label carve-out	May avoid use-patent infringement if technically and commercially workable
Settlement	Can establish a negotiated launch date
Later patent assertion	Can preserve a separate barrier after an earlier patent expires

A definitive assessment of each manufacturer's current litigation position requires the live docket and current Orange Book listing. The existence of an ANDA challenge does not itself establish invalidity or noninfringement.

How strong is the patent estate for pimavanserin?

US 8,921,393 is commercially meaningful but narrower than a composition-of-matter patent.

Strengths

It covers the active ingredient in a treatment method.
It reaches Parkinson's disease and secondary psychosis.
It includes broad dose ranges.
It includes daily and once-daily administration.
It identifies tartrate and hydrochloride salts.
It contains combination-treatment claims.
It aligns with the clinical and commercial positioning of Nuplazid.

Limitations

It does not claim pimavanserin as a chemical composition in the abstract.
It does not independently claim a tablet or capsule.
It does not expressly claim a particular commercial strength.
Method claims require proof of use and the relevant patient condition.
A generic applicant may attempt an indication carve-out.
Other patent-family members may carry longer or different terms.

The patent's enforceability also depends on ordinary validity grounds, including written description, enablement, anticipation, obviousness, indefiniteness and enforceability conduct. The claim set's broad disease language and overlapping dependent claims may be relevant to claim-construction and validity disputes, but the issued claims remain enforceable unless canceled, invalidated or disclaimed.

How does US 8,921,393 compare with formulation and composition patents?

Patent category	What it protects	Generic risk
Composition of matter	Pimavanserin molecule or defined chemical genus	Usually highest barrier; can block all uses
Salt or polymorph	Tartrate, hydrochloride or crystalline form	May block specific API supply routes
Formulation	Tablet, capsule, release profile or excipient system	Can be avoided through alternative formulation
Method of use	Treatment of neurodegenerative disease or psychosis	May be avoided through label carve-out, but induced-use risk remains
Manufacturing process	Synthesis, purification or crystallization	Can be avoided with a noninfringing process

US 8,921,393 is a method-of-use patent. It does not provide the same universal exclusionary scope as an unexpired composition-of-matter patent. Its commercial strength comes from the close relationship between the claimed indication and the FDA-approved Nuplazid label.

What generic launch scenarios exist?

Three launch scenarios are most relevant.

Launch after patent expiration

A generic applicant may launch after March 30, 2027, assuming no other unexpired patent, regulatory exclusivity period or settlement restriction blocks launch.

Launch with a carved-out label

An applicant may seek approval for non-patented indications while omitting protected uses under a section viii statement. This strategy depends on the final label, promotional conduct and whether the remaining indications have sufficient commercial value.

Launch after a successful Paragraph IV challenge

A generic may launch before patent expiration if it obtains a favorable judgment, the patent is disclaimed or invalidated, or the parties enter a settlement permitting earlier entry.

The most important commercial variable is not merely the expiration date of US 8,921,393. It is whether other Nuplazid patents extend effective protection beyond that date.

What are the geographic and manufacturing barriers?

US 8,921,393 has territorial effect only in the United States. It does not directly block manufacture, sale or use in Europe, Japan, Canada or other jurisdictions.

A global pimavanserin program requires separate review of:

Patent families in each target country
National-phase filings
Local patent-term rules
Supplementary protection certificates
Regulatory data exclusivity
Local formulation and process patents
Importation and supply-chain exposure

Manufacturing risk is separate from treatment-method risk. A manufacturer may avoid a US process patent but still face method-of-use liability if its label or marketing encourages a covered use. Conversely, a noninfringing manufacturing process does not eliminate Orange Book method-of-use exposure.

What is the revenue exposure associated with this patent?

Nuplazid is Acadia's commercial product for Parkinson's disease psychosis, making the patent estate strategically important to Acadia's revenue base. The protected use in US 8,921,393 overlaps with the product's core indication and approved once-daily administration.[3]

Revenue exposure depends on:

The share of Nuplazid sales attributable to the United States
The timing of generic approval
The number of approved generic manufacturers
Settlement launch dates
Generic substitution rates
Whether later patents survive challenge
Whether a carved-out label can attract pharmacy substitution
Prescriber reliance on the patented indication

The patent's expiration creates a potential generic-entry date, but the effective loss of exclusivity must be modeled against the full Orange Book estate and any negotiated launch restrictions.

Key Takeaways

US 8,921,393 is a pimavanserin method-of-use patent associated with Nuplazid.
The two independent claims cover treatment of neurodegenerative disease and treatment of secondary psychosis.
The patent covers Parkinson's disease, Alzheimer's disease and multiple additional neurodegenerative disorders.
Tartrate and hydrochloride salts are expressly claimed.
Daily and once-daily dosing are expressly claimed.
The dose limitations range from about 0.001 mg to about 50 mg, including 10 mg, 25 mg and 50 mg.
Combination use with dopaminergic, anti-dyskinesia, anti-dystonia, anti-tremor and antipsychotic agents is covered.
The projected expiration date is March 30, 2027.
The patent is not a composition-of-matter or formulation patent.
Generic launch risk depends on Paragraph IV litigation, label carve-outs, settlements and other Nuplazid patents.

Frequently Asked Questions

Does US 8,921,393 cover pimavanserin tartrate specifically?

Yes. Dependent claims expressly recite the tartrate salt, including claims directed to Parkinson's disease, Alzheimer's disease and psychosis secondary to a neurodegenerative disease.

Does the patent cover the 34 mg Nuplazid dose?

The patent's broad dose range extends to about 50 mg, which encompasses a 34 mg daily dose. The patent does not expressly identify 34 mg as a fixed-dose limitation.

Can a generic manufacturer avoid the patent by using pimavanserin hydrochloride?

Not necessarily. Claims 3 and 21 expressly identify the hydrochloride salt. A manufacturer must analyze the complete claim set and its proposed indication, dose and label.

Is US 8,921,393 a patent on the Nuplazid tablet?

No. It is primarily a method-of-treatment patent. Protection for a particular tablet formulation, crystalline form or manufacturing process would require separate claims or patents.

Does the patent block biosimilar competition?

No. Pimavanserin is a small-molecule drug, so competing products would generally proceed through the ANDA generic-drug pathway rather than the biosimilar pathway under the Public Health Service Act.

References

United States Patent and Trademark Office. (2014). US Patent No. 8,921,393 B2: Methods of treating neurodegenerative diseases.
Google Patents. (n.d.). US8921393B2: Methods of treating neurodegenerative diseases.
U.S. Food and Drug Administration. (2023). Nuplazid (pimavanserin tartrate) prescribing information. Acadia Pharmaceuticals Inc.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book. FDA.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	407117	⤷ Start Trial
Austria	512136	⤷ Start Trial
Australia	2004206886	⤷ Start Trial
Brazil	PI0406591	⤷ Start Trial
Canada	2512639	⤷ Start Trial
China	101780080	⤷ Start Trial
China	102028949	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 8,921,393

Summary for Patent: 8,921,393