Details for Patent: 9,074,256

Which drugs does patent 9,074,256 protect, and when does it expire?

Patent 9,074,256 protects BYSANTI and FANAPT and is included in two NDAs.

This patent has five patent family members in four countries.

Summary for Patent: 9,074,256

Title:	Method of predicting a predisposition to QT prolongation
Abstract:	The present invention describes an association between genetic polymorphisms in the ABCC2 gene and a predisposition to prolongation of the QT interval, and provides related methods for the prediction of such a predisposition, the administration of QT interval-prolonging compounds to individuals having such a predisposition, and determining whether a compound is capable of inducing QT prolongation.
Inventor(s):	Christian Lavedan, Simona Volpi, Louis Licamele
Assignee:	Vanda Pharmaceuticals Inc
Application Number:	US13/263,076
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 9,074,256
Patent Claim Types: see list of patent claims	Use;

US Patent 9,074,256: Iloperidone Pharmacogenomic Dosing Claims, Patent Scope and Market Risk

US Patent No. 9,074,256 protects a pharmacogenomic method for dosing iloperidone, or a specified iloperidone metabolite, according to the patient’s ABCC2 rs7067971 genotype. The core distinction is between patients with a GG genotype, who receive a lower quantity, and patients with non-GG genotypes, who receive a higher quantity. Claims 5-10 extend the method to individuals with long QT syndrome and expressly identify 24 mg/day as the higher iloperidone dose.

The patent does not claim iloperidone as a chemical compound. It claims a genotype-guided treatment protocol. Its commercial value therefore depends on whether a generic or branded product is marketed with dosing instructions, diagnostic services, prescribing systems, or clinical workflows that practice each required claim element.

What does US Patent 9,074,256 protect?

The patent protects the combination of four elements:

1. A human patient.
2. Administration of iloperidone or the specified iloperidone metabolite.
3. Determination of the patient’s ABCC2 genotype at rs7067971.
4. Administration of a lower dose for GG patients and a higher dose for non-GG patients.

The claims require a relationship between the genotype result and the administered quantity. A claim is not practiced merely because a patient has a particular ABCC2 genotype or receives iloperidone.

Claim-by-claim scope

Claim	Subject matter	Key limitation
1	Genotype-guided administration of iloperidone or metabolite	GG receives first, lower quantity; non-GG receives second, higher quantity
2	Claim 1 plus CYP2D6 testing	CYP2D6 genotype is determined
3	Claim 1 limited to iloperidone	Excludes metabolite-only use
4	Claim 1 limited to specified metabolite	Covers 1-[4-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-3-methoxyphenyl]ethanol
5	Genotype-guided administration in LQTS patients	Same GG/non-GG dose split, with LQTS population
6	Claim 5 plus CYP2D6 testing	Adds CYP2D6 determination
7	Claim 5 limited to iloperidone	LQTS plus iloperidone
8	Claim 5 limited to specified metabolite	LQTS plus metabolite
9	Claim 3 plus 24 mg/day second quantity	Non-GG iloperidone dose is 24 mg/day
10	Claim 7 plus 24 mg/day second quantity	LQTS, non-GG genotype, iloperidone at 24 mg/day

The broadest independent claim is claim 1. Claim 5 is narrower because it requires that the individual suffer from long QT syndrome. Claims 9 and 10 are narrower still because they specify 24 mg/day as the second quantity.

How does the ABCC2 rs7067971 limitation affect infringement?

The ABCC2 limitation is the central technical restriction. A potential infringer must determine, or have determined, the patient’s genotype at rs7067971 and use that result to select the dose.

The claim distinguishes:

• GG: lower quantity.
• Non-GG: higher quantity, covering AG and AA genotypes if the relevant allele notation is used in the conventional orientation.

The claims do not state a specific lower dose. This creates an asymmetry:

• The lower dose can vary, provided it is less than the second quantity.
• The higher dose must be greater than the first quantity.
• Claims 9 and 10 specifically require 24 mg/day as the second quantity.

A dosing protocol that gives every patient the same iloperidone dose does not satisfy the genotype-dependent limitation. A genetic test performed for research, risk assessment, or another clinical purpose may not establish infringement unless the test result is used in the claimed administration method.

“Determining or having determined” broadens the testing requirement

The phrase “determining or having determined” can reach situations in which:

• The prescribing physician orders the test.
• A laboratory previously generated the genotype result.
• The result is imported from an electronic health record.
• A third-party pharmacogenomic service performs the testing.
• A clinical decision-support platform uses a previously determined result.

The language does not require that the same entity perform the test and administer the drug. This creates potential divided-infringement issues involving laboratories, health systems, physicians, specialty pharmacies, and software providers.

What are the strongest and weakest claims in US 9,074,256?

Claim 1 is commercially broad but legally exposed to prior-art and subject-matter-eligibility arguments. It covers any human administration of iloperidone or the specified metabolite when dosing is selected by ABCC2 rs7067971 status.

Claims 9 and 10 are narrower but easier to map against a product label or prescribing protocol because they identify 24 mg/day.

Relative claim strength

Claim category	Breadth	Enforcement value	Principal vulnerability
Claim 1	High	High if genotype-guided dosing is documented	Prior art, written description, enablement, Section 101
Claim 2	Medium	Moderate	CYP2D6 test may be absent from routine practice
Claim 3	High within iloperidone use	High	Requires ABCC2-guided dosing
Claim 4	Narrow	Limited commercial market	Metabolite may not be marketed as a therapeutic product
Claim 5	Medium	Potentially high in LQTS population	Requires proof of LQTS
Claim 7	Medium	Moderate	Narrow patient population
Claims 9-10	Narrow	Stronger claim charting	Exact 24 mg/day and genotype-based selection must be shown

The patent’s practical strength is greatest if an approved label, clinical protocol, or computerized prescribing system expressly directs ABCC2 testing and uses the result to select a lower or higher iloperidone dose. It is weaker if genotype testing is not routine and dosing information remains individualized or undocumented.

What dose does the patent associate with non-GG patients?

Claims 9 and 10 identify 24 mg/day as the second quantity for iloperidone. Under these claims:

• GG patients receive a first quantity below 24 mg/day.
• Non-GG patients receive 24 mg/day.
• Claim 10 applies the same framework to patients with LQTS.

The claims do not define the first quantity. It could be any quantity less than 24 mg/day, subject to the patent’s construction and the requirements of the asserted claim.

The approved Fanapt label identifies 24 mg/day as the maximum recommended daily dose for adults with schizophrenia, normally administered as 12 mg twice daily. The label also contains important warnings concerning QT prolongation and CYP2D6-related exposure, but the label’s regulatory dosing instructions are not equivalent to an ABCC2 rs7067971 dosing directive. [2]

What is the relationship between US 9,074,256 and CYP2D6?

CYP2D6 is an additional limitation in claims 2 and 6. These claims require determining the patient’s CYP2D6 genotype, but the provided claims do not expressly require a particular CYP2D6 phenotype or a particular dose adjustment based on CYP2D6.

That distinction matters. Claims 2 and 6 do not, on their face, require:

• A CYP2D6 poor-metabolizer result.
• A CYP2D6 intermediate-metabolizer result.
• A CYP2D6-specific dose.
• Use of the CYP2D6 result in the dose decision.

They require genotype determination in addition to the ABCC2-based dosing method.

The FDA label identifies CYP2D6 metabolism as relevant to iloperidone exposure and recommends a lower maximum dose for patients who are CYP2D6 poor metabolizers or who receive strong CYP2D6 inhibitors. [2] Those FDA instructions are pharmacokinetic and safety-related. The patent claims add a separate ABCC2 genotype-based dosing rule.

Does the patent cover iloperidone’s active metabolite?

Yes. Claims 1, 4, 5, and 8 cover the specified iloperidone metabolite. The metabolite is identified by chemical structure and name:

1-[4-[3-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-3-methoxyphenyl]ethanol.

The metabolite claims are narrower than the iloperidone claims because they do not cover every possible iloperidone metabolite. A product containing a different metabolite would not fall within claim 4 or claim 8 solely because it is pharmacologically related to iloperidone.

The commercial importance of these claims depends on whether the metabolite is administered as a therapeutic product, prodrug, active pharmaceutical ingredient, or clinically relevant combination product. The standard Fanapt product is iloperidone, not the metabolite identified in claims 4 and 8. [2]

What does the LQTS limitation add?

Claims 5-8 apply the dosing method to a patient suffering from long QT syndrome. LQTS is a narrower clinical population than all human patients.

The LQTS claims potentially address a higher-risk population because iloperidone can prolong the QT interval. The FDA label warns against use in patients with known arrhythmias, congenital long QT syndrome, or a history of cardiac arrhythmias, and it identifies circumstances requiring avoidance or caution. [2]

This produces a regulatory tension:

• The patent claims a dosing method for LQTS patients.
• The FDA labeling includes significant restrictions and warnings for patients with QT-prolongation risk.
• A patent claim does not establish that the claimed use is FDA-approved.
• A generic product may face regulatory and patent issues if the claimed LQTS use is absent from its label.

The LQTS limitation may reduce direct infringement exposure because the patent owner must establish that the treated individual falls within the claimed population. It can also create inducement risk if prescribing materials expressly recommend the claimed regimen for LQTS patients.

What is the Orange Book status of US Patent 9,074,256?

A method-of-use patent can be listed in the FDA Orange Book if it claims an approved method of using the drug and the patent holder submits it for listing under the applicable FDA rules. The Orange Book listing, rather than the patent text alone, determines whether an ANDA applicant must address the patent through a Paragraph IV certification or a section viii statement. [3]

The relevant regulatory questions are:

Question	Impact
Is US 9,074,256 listed for Fanapt or iloperidone?	Determines whether an ANDA applicant must address it
What use code accompanies the listing?	Defines the approved method of use associated with the patent
Does the approved label describe ABCC2 testing?	Affects section viii and induced-infringement analysis
Does the patent claim an approved LQTS use?	Determines whether the LQTS claims align with an Orange Book use code
Is the patent expired, delisted, or subject to a terminal disclaimer?	Affects the remaining regulatory barrier

The patent claims themselves do not establish Orange Book listing status. That status must be confirmed in the FDA’s current Approved Drug Products with Therapeutic Equivalence Evaluations database and the product-specific patent listing data. [3]

When does US Patent 9,074,256 lose exclusivity?

US 9,074,256 issued on July 7, 2015. Its effective term is generally 20 years from the earliest relevant nonprovisional application filing date, subject to patent-term adjustment, patent-term extension, terminal disclaimers, and any applicable statutory corrections. [1, 4]

The patent record should be read for:

• Earliest effective nonprovisional filing date.
• Continuation or divisional status.
• Patent-term adjustment.
• Terminal disclaimer.
• Reexamination or post-grant amendments.
• Patent-term extension under 35 U.S.C. § 156.

The patent is not an ordinary compound patent. Its expiration date does not determine whether all iloperidone exclusivity ends on the same date. Compound, formulation, manufacturing, and method-of-use patents can have different terms.

Exclusivity timeline for iloperidone

Event	Significance
2009 FDA approval of Fanapt	Established the original approved iloperidone product
2014 end of five-year NCE exclusivity	Opened the principal ANDA pathway, subject to listed patents
July 7, 2015 issuance of US 9,074,256	Added the asserted pharmacogenomic method patent
Patent-term expiration	Depends on the effective filing date and PTA/PTE records
Generic approval or launch	Depends on ANDA certifications, litigation, settlements, and label scope

The patent should not be characterized as providing a new chemical entity exclusivity period. Its value is patent-based and use-specific.

Which companies have challenged iloperidone patents?

The most significant public iloperidone patent litigation involved Vanda Pharmaceuticals and West-Ward Pharmaceuticals, now associated with Hikma Pharmaceuticals. The Federal Circuit addressed Vanda’s iloperidone pharmacogenomic patent claims in Vanda Pharmaceuticals Inc. v. West-Ward Pharmaceuticals International Ltd., 887 F.3d 1117 (Fed. Cir. 2018). [5]

The Federal Circuit upheld the validity of the asserted treatment-method claims against the principal Section 101 challenge. The decision is important for US 9,074,256 because it supports the general proposition that a treatment claim requiring a patient-specific test result followed by administration of a specified dose can be patent-eligible when the claim is directed to a treatment method rather than merely a natural law.

The case does not automatically validate every claim of US 9,074,256. Claim-by-claim analysis remains necessary, particularly for:

• The ABCC2 rs7067971 limitation.
• The GG versus non-GG dosing rule.
• The LQTS population.
• The 24 mg/day limitation.
• Written-description support for the claimed genotype-response relationship.
• Enablement across the full scope of the claims.

Public litigation involving iloperidone generics should be separated into two categories:

1. Challenges to core or pharmacogenomic patents.
2. Commercial settlement arrangements governing the date and conditions of generic entry.

A Paragraph IV certification is not itself proof that a generic product will launch. FDA approval, litigation outcomes, settlement terms, pediatric exclusivity, and potential at-risk-launch exposure all affect the result.

How does US 9,074,256 compare with the core iloperidone patent estate?

US 9,074,256 is a late-stage, precision-dosing patent. It differs materially from patents directed to the iloperidone molecule, dosage forms, or manufacturing processes.

Patent category	Typical protected subject matter	Relevance to generic entry
Compound patent	Iloperidone chemical structure	Usually the earliest and broadest patent barrier
Polymorph or solid-state patent	Crystalline form, purity, stability	Can affect API sourcing
Formulation patent	Tablet composition, release profile, excipients	Can constrain formulation design
Method-of-use patent	Schizophrenia, LQTS, genotype-guided dosing	Can affect label and prescribing conduct
Pharmacogenomic patent	ABCC2 or CYP2D6-based treatment selection	Creates diagnostic and induced-infringement issues
Manufacturing patent	Synthesis, purification, intermediates	May require process redesign or licensing

The patent’s claim scope is narrower than a compound patent but can be harder to design around if a manufacturer, prescriber, or digital health platform uses the specific ABCC2 algorithm.

What formulation patents protect Fanapt or iloperidone products?

The provided claims do not cover:

• Tablet composition.
• Excipients.
• Particle size.
• Crystalline form.
• Dissolution profile.
• Modified release.
• Packaging.
• Manufacturing process.
• Bioequivalence criteria.

They cover administration decisions based on genotype.

For a complete freedom-to-operate review, the relevant patent family should be searched separately from US 9,074,256 for:

• Iloperidone compound patents.
• Solid-state and polymorph patents.
• Oral dosage-form patents.
• Combination products.
• Metabolite patents.
• Process patents.
• Diagnostic kit patents.
• Software or clinical decision-support claims.

The existence of US 9,074,256 does not establish that a generic manufacturer can use the same formulation, process, or tablet design without reviewing those separate patent families.

What generic launch risks exist for iloperidone?

The primary generic risks are label-driven rather than molecule-driven.

Skinny-label risk

If the approved label does not include the patented ABCC2-guided dosing method, an ANDA applicant may attempt a section viii statement to carve out the patented use. That strategy depends on the exact Orange Book use code and the remaining unpatented indications.

A carve-out is less effective if the generic label, medical-information materials, decision-support tools, or promotional conduct still encourage the patented method.

Induced infringement risk

Potential evidence may include:

• Label language directing ABCC2 testing.
• Prescriber guides.
• Pharmacogenomic dosing algorithms.
• Laboratory ordering pathways.
• Electronic prescribing alerts.
• Reimbursement instructions.
• Specialty pharmacy protocols.
• Sales training or medical-affairs materials.

The patent owner would need to show that the generic manufacturer actively encourages the claimed conduct and that the underlying method is performed.

At-risk launch

A generic could launch before final resolution of all patent disputes, exposing the manufacturer to damages and injunctive relief if the patent is later held valid and infringed. The commercial decision would depend on expected sales, remaining patent term, litigation probability, and the availability of a non-infringing label.

How strong is the patent estate for iloperidone?

The estate is strongest where four conditions converge:

1. The patent is listed in the Orange Book.
2. The approved label or clinical practice uses ABCC2 testing.
3. The generic label or associated materials encourage the genotype-based dosing method.
4. The patent survives validity and claim-construction challenges.

Its strength is lower where:

• ABCC2 testing is not part of routine Fanapt prescribing.
• The FDA label does not describe the claimed method.
• The generic uses a carved-out label.
• The generic does not offer or promote pharmacogenomic testing.
• The relevant patent is not Orange Book-listed.
• The patent term is near expiration.
• Physicians independently choose dosing without following the claimed algorithm.

The Federal Circuit’s Vanda decision improves the legal posture of patient-specific dosing claims under Section 101, but it does not eliminate risks under Sections 102, 103, 112, or 271. [5]

What licensing or settlement issues affect iloperidone?

Iloperidone commercialization has involved Vanda Pharmaceuticals as the principal US innovator company. Generic entry negotiations may include:

• Early-entry dates.
• No-launch periods.
• Authorized-generic arrangements.
• Patent-claim releases.
• Covenants not to sue.
• Geographic restrictions.
• Product-specific carve-outs.
• Restrictions on pharmacogenomic labeling.

Settlement terms are often confidential or only partially reflected in court filings. A settlement does not establish patent validity. It establishes the parties’ agreed commercial risk allocation.

Any transaction involving iloperidone should distinguish between:

• Rights to sell iloperidone tablets.
• Rights to practice patented dosing methods.
• Rights to use pharmacogenomic test results.
• Rights to commercialize diagnostic services.
• Rights to use trademarks or regulatory dossiers.
• Rights to manufacture API or finished dosage forms.

What geographic coverage does US 9,074,256 provide?

US 9,074,256 provides rights only under US patent law. It does not automatically protect genotype-guided iloperidone dosing in:

• Europe.
• Canada.
• Japan.
• China.
• Australia.
• Latin America.
• Other jurisdictions.

Foreign counterparts must be reviewed independently for claim scope, prosecution amendments, grant status, and expiration. Patent protection may differ because:

• Some jurisdictions restrict diagnostic or treatment-method claims.
• Claim language may be directed to a kit, pharmaceutical composition, or use rather than a method of treatment.
• National-phase applications may have been abandoned.
• Patent-term calculations differ.
• Patent eligibility standards vary.

A global launch assessment cannot treat US 9,074,256 as a worldwide barrier.

Key Takeaways

• US 9,074,256 is a pharmacogenomic method patent, not an iloperidone compound patent.
• Its core requirement is ABCC2 rs7067971 testing followed by a lower dose for GG patients and a higher dose for non-GG patients.
• Claims 2 and 6 add CYP2D6 genotype determination but do not expressly require a particular CYP2D6 phenotype or dose.
• Claims 5-10 narrow the method to patients with long QT syndrome.
• Claims 9 and 10 expressly identify 24 mg/day as the second iloperidone quantity.
• The patent’s commercial effect depends heavily on Orange Book listing, use-code wording, FDA labeling, and generic promotional conduct.
• The Federal Circuit’s Vanda decision supports the patent-eligibility of individualized dosing claims, but it does not resolve every validity or infringement issue for this patent.
• Separate compound, formulation, polymorph, manufacturing, metabolite, and diagnostic patents must be analyzed for a complete iloperidone freedom-to-operate review.
• US 9,074,256 has only US territorial effect. Foreign patent families require separate analysis.

FAQs

Does US 9,074,256 prevent a generic from selling ordinary iloperidone tablets?

Not automatically. The patent claims a genotype-guided method of administration. A generic may face infringement risk if its label or commercial conduct encourages ABCC2 testing and the claimed GG/non-GG dosing protocol.

Is 24 mg/day required for every non-GG patient?

Only claims 9 and 10 expressly require 24 mg/day as the second quantity. Independent claims 1 and 5 require a higher second quantity but do not specify its exact amount.

Does the patent cover CYP2D6-guided iloperidone dosing by itself?

No. Claims 2 and 6 require CYP2D6 genotype determination in addition to the ABCC2-based dosing method. The provided claims do not independently claim CYP2D6-only dosing.

Can a laboratory infringe US 9,074,256 by performing an ABCC2 test?

Testing alone does not practice the complete treatment method. Risk may arise if the laboratory participates in a coordinated workflow that determines the genotype and supports administration of iloperidone according to the claimed dose rule.

Does the Vanda v. West-Ward decision prove that US 9,074,256 is valid?

No. The decision supports the eligibility of certain individualized iloperidone dosing claims under Section 101. Validity and infringement of US 9,074,256 must be assessed against its own prosecution history, prior art, claim language, and accused conduct.

References

1. United States Patent and Trademark Office. (2015). US Patent No. 9,074,256, methods of administering iloperidone based on ABCC2 genotype.
2. U.S. Food and Drug Administration. (2022). Fanapt (iloperidone) prescribing information.
3. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book.
4. United States Code. (2023). 35 U.S.C. §§ 154, 156, 271.
5. Vanda Pharmaceuticals Inc. v. West-Ward Pharmaceuticals International Ltd., 887 F.3d 1117 (Fed. Cir. 2018).

Drugs Protected by US Patent 9,074,256

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Vanda Pharms Inc	BYSANTI	milsaperidone	TABLET;ORAL	220358-001	Feb 20, 2026		RX	Yes	Yes	9,074,256					METHOD FOR ACUTE TREATMENT OF MANIC OR MIXED EPISODES ASSOCIATED WITH BIPOLAR I DISORDER IN ADULTS BY ADMINISTERING MILSAPERIDONE TO A PATIENT BY LOWERING THE DOSE AFTER DETERMINING THAT THE PATIENT HAS A GENETIC PREDISPOSITION FOR QT PROLONGATION
Vanda Pharms Inc	BYSANTI	milsaperidone	TABLET;ORAL	220358-001	Feb 20, 2026		RX	Yes	Yes	9,074,256					METHOD FOR TREATMENT OF SCHIZOPHRENIA IN ADULTS BY ADMINISTERING MILSAPERIDONE TO A PATIENT BY LOWERING THE DOSE AFTER DETERMINING THAT THE PATIENT HAS A GENETIC PREDISPOSITION FOR QT PROLONGATION
Vanda Pharms Inc	BYSANTI	milsaperidone	TABLET;ORAL	220358-002	Feb 20, 2026		RX	Yes	No	9,074,256					METHOD FOR ACUTE TREATMENT OF MANIC OR MIXED EPISODES ASSOCIATED WITH BIPOLAR I DISORDER IN ADULTS BY ADMINISTERING MILSAPERIDONE TO A PATIENT BY LOWERING THE DOSE AFTER DETERMINING THAT THE PATIENT HAS A GENETIC PREDISPOSITION FOR QT PROLONGATION

Foreign Priority and PCT Information for Patent: 9,074,256

PCT Information
PCT Filed	April 05, 2010	PCT Application Number:	PCT/US2010/029943
PCT Publication Date:	October 14, 2010	PCT Publication Number:	WO2010/117941

International Family Members for US Patent 9,074,256

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Canada	2757723
European Patent Office	2416778
Japan	2012522534