Details for Patent: 9,241,935

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Which drugs does patent 9,241,935 protect, and when does it expire?

Patent 9,241,935 protects SUBSYS and is included in one NDA.

This patent has nine patent family members in nine countries.

Summary for Patent: 9,241,935

Title:	Sublingual fentanyl spray
Abstract:	The present invention is directed to sublingual formulations containing fentanyl, a pharmaceutically acceptable sale thereof, or derivative thereof, suitable for administration to a patient, and methods for treatment with the formulations.
Inventor(s):	S. George Kottayil, Venkat R. Goskonda, Zhongyuan Zhu, Linet Kattookaran, Neha Parikh
Assignee:	Btcp Pharma LLC
Application Number:	US14/448,752
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 9,241,935
Patent Claim Types: see list of patent claims	Formulation; Compound;

United States Drug Patent 9,241,935: Scope, Claim Construction, Expiration and Fentanyl Patent Landscape

U.S. Patent No. 9,241,935 protects a sublingual fentanyl spray defined primarily by human pharmacokinetic performance rather than by a specific excipient composition, device, concentration, or manufacturing process. The asserted commercial value lies in claims covering the exposure profile of a sublingually delivered fentanyl product, including AUClast, AUCinf, AUCextrap and dose proportionality.

The claims are narrow in subject matter but potentially difficult to design around if a competing product produces the claimed human PK profile. Their main vulnerabilities are the use of numerical pharmacokinetic boundaries, the unusual wording of claim 3, potential indefiniteness around "substantially dose proportional," and the need to prove infringement through human clinical data.

What does U.S. Patent 9,241,935 cover?

U.S. Patent No. 9,241,935, titled "Sublingual Fentanyl Spray," was granted on January 26, 2016. The patent concerns a fentanyl formulation administered through the sublingual route and characterized by specified pharmacokinetic results in humans.[1]

The independent claims do not require a particular:

• Fentanyl concentration
• Spray volume
• Propellant
• Solvent
• Buffer
• Surfactant
• Mucoadhesive
• Container or actuator
• Number of sprays
• Manufacturing process
• Therapeutic indication

Instead, the claims use pharmacokinetic limitations as the principal boundary of the invention.

Claim	Core limitation	Primary legal function
1	Sublingual fentanyl spray producing at least one specified PK result	Product-by-performance claim
2	Sublingual fentanyl spray with substantially dose-proportional mean AUClast	Dose-response performance claim
3	Sublingual fentanyl spray producing a specified mean F(AUClast)	Bioavailability-performance claim

The claims cover fentanyl free base and pharmaceutically acceptable salts where expressly stated. Because the formulation is claimed as a spray, a tablet, lozenge, buccal film or injectable product would not ordinarily fall within the literal scope of these claims.

How should claim 1 be construed?

Claim 1 covers:

A sublingual spray formulation comprising a dose of fentanyl that provides one or more of the following mean pharmacokinetic values when administered to humans:

• AUClast: 4.863 ± 1.70821 hr·ng/mL
• AUCinf: 5.761 ± 1.916 hr·ng/mL
• AUCextrap: 10.26 ± 5.66%

The phrase "one or more" is important. A product may potentially satisfy claim 1 by meeting any one of the listed PK limitations, rather than all three. The claim is therefore broader than a claim requiring simultaneous conformity with AUClast, AUCinf and AUCextrap.

What are the apparent numerical ranges?

If the plus-or-minus values are treated as claim boundaries, the nominal ranges are:

Parameter	Mean	Deviation	Approximate range
AUClast	4.863 hr·ng/mL	1.70821	3.15479 to 6.57121
AUCinf	5.761 hr·ng/mL	1.916	3.845 to 7.677
AUCextrap	10.26%	5.66	4.60% to 15.92%

The patent claim language should control over a purely mathematical reconstruction. A court would need to determine whether the "±" notation defines a range, identifies a reported mean and standard deviation, or incorporates the statistical presentation used in the specification and clinical study.

That issue matters because pharmacokinetic results vary with:

• Fentanyl dose
• Sampling schedule
• Analytical assay
• Subject population
• Fed or fasted state
• Administration technique
• Spray location
• Number of administrations
• Treatment period
• Statistical method
• Handling of below-quantification-limit samples

A competing product may produce a similar mean but fall outside the claimed range under a different protocol. Conversely, the patent holder may argue that the claim requires the product's performance under the protocol disclosed in the patent, rather than under any arbitrary study design.

What does claim 2 protect?

Claim 2 covers a sublingual fentanyl spray that provides a "substantially dose proportional mean AUClast" based on a mean AUClast of approximately 4.863 ± 1.70821 hr·ng/mL.

This claim adds a dose-response requirement. It is not limited solely to a single exposure value. The accused product must also show that AUClast increases in a substantially proportional relationship as the fentanyl dose increases.

The phrase "substantially dose proportional" is potentially contested because it does not specify:

• The tested dose range
• The number of dose levels
• The permitted deviation from linearity
• The statistical test
• The acceptable confidence interval
• Whether proportionality concerns individual subjects or group means
• Whether the relationship is assessed on a log scale

The specification and prosecution history would likely be central to construction. If the patent provides a defined clinical protocol or statistical standard, that disclosure may narrow the practical scope of the term. If no objective standard was supplied, an accused infringer could raise an indefiniteness challenge under 35 U.S.C. §112(b).[2]

What does claim 3 protect?

Claim 3 covers a sublingual fentanyl spray that provides a mean "F(AUClast)" of approximately 0.721 ± 0.199 ng/mL.

The wording presents two issues.

First, "F(AUClast)" is not a conventional standalone pharmacokinetic unit in the same way as AUClast. F generally denotes bioavailability, while AUClast is an exposure measure. The recited unit, ng/mL, also does not correspond naturally to an area-under-the-curve measurement, which is usually expressed as time multiplied by concentration.

Second, the claim does not define the comparator or calculation method for F. Depending on the specification, F could refer to:

• Absolute bioavailability
• Relative bioavailability
• A normalized exposure value
• A calculated fraction of dose reaching systemic circulation
• A study-specific parameter

The claim may still be enforceable if the patent specification gives a clear definition and a person skilled in pharmacokinetics could determine whether a product meets the limitation. Without that definition, claim 3 is more exposed than claims 1 and 2 to indefiniteness and written-description arguments.

What formulation characteristics are protected?

The claims protect performance of the finished sublingual spray, not a defined formulation recipe. This creates broad freedom for formulation design within the claim's functional boundary.

A competing product could use different:

• Solvent systems
• pH modifiers
• Preservatives
• Flavoring agents
• Viscosity modifiers
• Delivery-device geometries
• Metered-dose volumes
• Fentanyl salt forms

Those differences would not avoid infringement if the resulting product is a sublingual spray containing fentanyl and produces the claimed PK result.

Conversely, a formulation with substantially identical excipients could avoid literal infringement if it does not meet the claimed PK limitations. That makes the patent different from a conventional composition claim, which is infringed by the presence of specified ingredients regardless of observed clinical performance.

When does U.S. Patent 9,241,935 expire?

The patent was granted in 2016, but its enforceable term is determined by the earliest effective nonprovisional priority date, subject to patent-term adjustment and any applicable patent-term extension.

The patent family is associated with the development of sublingual fentanyl spray products and has a term extending into the late 2020s. A precise expiration date requires the USPTO patent-term record and the complete priority chain. The grant date alone cannot establish the expiration date.[3]

For commercial planning, the relevant exclusivity window is the patent's adjusted expiration date, not the 20th anniversary of the grant. Any terminal disclaimer, patent-term adjustment, patent-term extension, or disclaimed period could change the date.

What is the Orange Book status of U.S. Patent 9,241,935?

Patent 9,241,935 is associated with the sublingual fentanyl product marketed as Subsys, which was approved by FDA as a sublingual spray containing fentanyl citrate for breakthrough cancer pain in opioid-tolerant adults.[4]

The Orange Book analysis requires separation of three questions:

1. Whether the patent is listed for the reference product.
2. Whether the listed patent is a drug-substance, drug-product or method-of-use patent.
3. Whether the patent has an expiration date that remains relevant to an ANDA applicant.

A patent's presence in the Orange Book does not itself establish that every claim is infringed by every generic product. It determines the patent-certification framework applicable to an ANDA applicant under 21 U.S.C. §355(j).[5]

For a generic sublingual fentanyl spray, the relevant listed patents may include formulation, delivery-system, method-of-use and pharmacokinetic claims. Patent 9,241,935 is particularly significant if listed as a product or formulation patent because a Paragraph IV certification could trigger litigation and a potential 30-month stay.

What Paragraph IV challenges and generic entry risks exist?

A generic applicant seeking approval for a sublingual fentanyl spray would generally need to address each Orange Book-listed patent through one of four certifications:

• Paragraph I: no patent information has been filed
• Paragraph II: the patent has expired
• Paragraph III: approval will occur after patent expiration
• Paragraph IV: the patent is invalid, unenforceable or will not be infringed

A Paragraph IV challenge to patent 9,241,935 would likely focus on several arguments.

Noninfringement

The applicant could argue that its product does not produce the claimed AUClast, AUCinf, AUCextrap or F(AUClast) values. This would require reliable clinical or comparative pharmacokinetic evidence.

The applicant could also argue that its dosage form is not a "sublingual spray," particularly if the product is primarily buccal, oropharyngeal or swallowed after administration.

Indefiniteness

The strongest textual targets are:

• "Substantially dose proportional"
• "About"
• The plus-or-minus notation
• "F(AUClast)"
• The absence of a defined PK testing protocol

A court may uphold these terms if the specification supplies objective boundaries. Otherwise, the claims could be vulnerable under §112(b).

Lack of written description or enablement

An invalidity challenge could assert that the patent claims an unduly broad universe of fentanyl sprays based on limited clinical examples. The challenger would need to show that the patent does not demonstrate possession of the full claimed scope or that substantial experimentation would be required to produce the claimed PK profile across the range of covered formulations.

Obviousness

A challenger could combine prior-art fentanyl sprays, sublingual delivery systems and known PK targets. The patent holder would likely respond that the claimed exposure profile depended on formulation and delivery characteristics that were not predictable from the prior art.

Which companies are relevant to the patent landscape?

The principal commercial entity historically associated with Subsys was Insys Therapeutics, Inc. The product was commercialized for a restricted indication and later became subject to substantial regulatory, compliance and commercial scrutiny.

The competitive landscape includes:

Category	Relevant products or companies	Patent relevance
Sublingual fentanyl spray	Subsys, historically associated with Insys	Direct reference-product technology
Buccal fentanyl tablets	Fentora and generic fentanyl buccal tablets	Different dosage form and patent estate
Transmucosal lozenges	Actiq and generic equivalents	Different delivery technology
Buccal films	Onsolis and related products	Separate formulation and delivery claims
Injectable fentanyl	Generic injectable fentanyl manufacturers	Generally outside the sublingual-spray claims
Intranasal fentanyl	Nasal spray developers and manufacturers	Different route and potentially different patent families

The principal design-around opportunity is route and dosage form. A generic or follow-on product that is not a sublingual spray may avoid the literal scope of patent 9,241,935 while still competing in the broader fentanyl market.

How strong is the patent estate for sublingual fentanyl spray?

Patent 9,241,935 has meaningful commercial leverage because it claims clinical performance that a generic applicant may need to reproduce for therapeutic equivalence. Its strength is greatest where:

• The product is clearly administered sublingually.
• The generic uses a comparable fentanyl dose.
• The formulation generates similar exposure.
• The patent is listed in the Orange Book.
• The claims survive construction of the PK terminology.

Its weaknesses are equally specific:

• The claims do not identify a concrete formulation recipe.
• Human PK results can vary between studies.
• The claim boundaries may depend on statistical interpretation.
• Claim 3 contains unusual terminology.
• A product can potentially design around the claims through a different exposure profile or delivery route.
• The commercial value depends on remaining patent term and the regulatory status of the reference product.

The patent is therefore stronger as an ANDA litigation asset than as a broad blocking patent over all fentanyl transmucosal products.

What manufacturing and intellectual-property barriers remain?

The patent does not appear, from the supplied claims, to impose a manufacturing-process restriction. A competitor could use a different production method if its finished product falls outside the claimed formulation and PK limitations.

Practical barriers may still arise from:

• Controlled-substance handling requirements
• Fentanyl containment and diversion controls
• Metered-dose spray reproducibility
• Uniform dose delivery
• Stability and preservative compatibility
• Sublingual deposition
• Clinical PK matching
• FDA abuse-deterrence and risk-management expectations
• Manufacturing controls for low-dose potent opioids

These regulatory and operational barriers are separate from the patent claims. They can delay market entry even when a patent challenge is successful.

What litigation and settlement information affects this patent?

The claim text alone does not establish the current litigation, settlement or licensing status of patent 9,241,935. Such status must be determined from the federal court docket, FDA patent listings, USPTO assignment records and any publicly filed ANDA litigation documents.

A settlement could affect:

• The earliest authorized generic-entry date
• A license to market after patent expiration
• Authorized-generic arrangements
• Product-specific manufacturing rights
• Restrictions on launch, distribution or indication

No settlement term should be inferred solely from the patent's grant record.

Key Takeaways

• Patent 9,241,935 is a sublingual fentanyl spray patent based primarily on human PK performance.
• Claim 1 can potentially be satisfied by any one of the listed PK parameters.
• Claim 2 adds a dose-proportionality requirement and is vulnerable to disputes over the meaning of "substantially."
• Claim 3 presents the greatest interpretation risk because "F(AUClast)" and its units are unusual.
• The claims do not require a specific excipient composition, device, concentration or manufacturing process.
• An ANDA applicant would likely focus on noninfringement, indefiniteness, written description, enablement and obviousness.
• The patent is relevant to generic sublingual fentanyl-spray entry, but it does not broadly cover all fentanyl transmucosal products.
• Exact patent expiration, current Orange Book listing and litigation status require verification against current USPTO, FDA and court records.

FAQs About U.S. Patent 9,241,935

Does patent 9,241,935 cover all fentanyl sprays?

No. The claims require a sublingual spray formulation and specified human pharmacokinetic performance. Nasal, injectable, buccal and other fentanyl products generally fall outside the literal claim language.

Can a generic avoid patent 9,241,935 by changing the fentanyl salt?

Not necessarily. Claim 2 expressly includes fentanyl free base and pharmaceutically acceptable salts. A salt change would not avoid infringement if the product otherwise meets the claim limitations.

Is patent 9,241,935 a formulation patent or a method-of-use patent?

It is best characterized as a product-by-performance formulation patent. The claims are directed to a sublingual spray formulation, although they rely on administration to humans to define the required performance.

Does FDA approval prove infringement of patent 9,241,935?

No. FDA approval and patent infringement are separate determinations. Approval may require a patent certification, but infringement depends on claim construction and the characteristics of the accused product.

Can a Paragraph IV challenge invalidate the entire Subsys patent estate?

No. A Paragraph IV challenge is patent-specific and claim-specific. A successful challenge to patent 9,241,935 would not automatically invalidate separate formulation, device, method-of-use or manufacturing patents.

References

1. United States Patent and Trademark Office. (2016). Sublingual fentanyl spray, U.S. Patent No. 9,241,935 B2.

2. United States Code. (2023). 35 U.S.C. §112: Specification.

3. United States Patent and Trademark Office. (2024). Manual of Patent Examining Procedure, Chapter 2700: Patent term.

4. U.S. Food and Drug Administration. (2012). Subsys prescribing information.

5. United States Code. (2023). 21 U.S.C. §355: New drugs and abbreviated new drug applications.

Drugs Protected by US Patent 9,241,935

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Btcp Pharma	SUBSYS	fentanyl	SPRAY;SUBLINGUAL	202788-001	Jan 4, 2012		DISCN	Yes	No			Y
Btcp Pharma	SUBSYS	fentanyl	SPRAY;SUBLINGUAL	202788-002	Jan 4, 2012		DISCN	Yes	No			Y
Btcp Pharma	SUBSYS	fentanyl	SPRAY;SUBLINGUAL	202788-003	Jan 4, 2012		DISCN	Yes	No			Y
Btcp Pharma	SUBSYS	fentanyl	SPRAY;SUBLINGUAL	202788-004	Jan 4, 2012		DISCN	Yes	No			Y
Btcp Pharma	SUBSYS	fentanyl	SPRAY;SUBLINGUAL	202788-005	Jan 4, 2012		DISCN	Yes	No			Y
Btcp Pharma	SUBSYS	fentanyl	SPRAY;SUBLINGUAL	202788-006	Aug 30, 2012		DISCN	Yes	No			Y

International Family Members for US Patent 9,241,935

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2008282743
Canada	2698749
Denmark	2180844
European Patent Office	2180844
Spain	2668366
Norway	2180844