Details for Patent: 9,642,844

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Which drugs does patent 9,642,844 protect, and when does it expire?

Patent 9,642,844 protects SUBSYS and is included in one NDA.

This patent has nine patent family members in nine countries.

Summary for Patent: 9,642,844

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:	US14/966,301
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 9,642,844
Patent Claim Types: see list of patent claims	Use; Formulation; Compound;

US Patent 9,642,844: Fentanyl Sublingual Spray Claims, Patent Scope and Generic-Entry Risk

US Patent 9,642,844 protects a narrow fentanyl sublingual spray profile combining defined concentrations of fentanyl, ethanol and propylene glycol with propellant-free delivery, droplet-size requirements and human pharmacokinetic performance. The patent is most relevant to products resembling Insys Therapeutics’ Subsys fentanyl sublingual spray, although the claims are not limited to the Subsys trade name, a specific spray device or fentanyl citrate.

The primary infringement risk is highest for a propellant-free sublingual fentanyl spray using 50% to 60% ethanol, 4% to 6% propylene glycol, droplets averaging at least 10 microns and pharmacokinetic characteristics approximating the claimed Tmax, Cmax, AUC and absorption profile.

What does US Patent 9,642,844 protect?

US Patent 9,642,844 protects a sublingual spray formulation for pain treatment. Independent claim 1 requires all of the following:

Claim element	Required limitation
Active ingredient	Fentanyl, a free base, pharmaceutically acceptable salt or, in dependent claims, a derivative
Fentanyl concentration	About 0.1% to about 0.8% by weight
Ethanol	About 50% to about 60% by weight
Propylene glycol	About 4% to about 6% by weight
Delivery	Sublingual spray
Propellant	Propellant-free
Droplets	Mean diameter of at least about 10 microns
Pharmacokinetics	Mean Tmax of about 1.28 ± 0.60, as stated in claim 1

The claim does not require a particular fentanyl salt, container, actuator, pump, nozzle geometry, preservative, flavoring agent or water content. Claim 16 expressly permits water, but water is not required by independent claim 1.

The formulation ranges leave room for other excipients. The claimed percentages do not total 100%, so the claim can cover compositions containing water and additional solvents, stabilizers, flavoring agents or other inactive ingredients, provided the required limitations remain satisfied.

How do the independent claims differ?

Claims 1 and 21 are the two independent formulation claims.

Feature	Claim 1	Claim 21
Fentanyl	0.1% to 0.8% by weight	0.1% to 0.8% by weight
Ethanol	50% to 60% by weight	50% to 60% by weight
Propylene glycol	4% to 6% by weight	4% to 6% by weight
Propellant-free	Yes	Yes
Mean droplet size	At least about 10 microns	At least about 10 microns
PK limitation	Mean Tmax of about 1.28 ± 0.60	About 10 minutes to 60% of maximum plasma concentration
LLOQ limitation	Not required	Mean LLOQ time of about 5 minutes

Claim 21 is narrower in its pharmacokinetic requirements but may provide a separate enforcement route where a product reaches 60% of maximum fentanyl plasma concentration in about 10 minutes and reaches the lower limit of quantification in approximately five minutes.

What concentrations and dosage strengths are covered?

Claims 2 and 3 define fentanyl concentrations of approximately 1 mg/mL to 8 mg/mL. Claim 3 identifies five nominal concentrations:

• 1 mg/mL
• 2 mg/mL
• 4 mg/mL
• 6 mg/mL
• 8 mg/mL

Claims 5, 7, 10, 11, 12, 13, 14, 15, 17 and 18 focus on dose strengths and PK performance at 100, 200, 400, 600 and 800 micrograms.

The 400-microgram dose is the principal reference point. The claims identify:

Parameter	Claimed 400-microgram result
Mean Cmax	0.813 ± 0.252 ng/mL
Mean AUClast	4.863 ± 1.70821 hr·ng/mL
Mean AUCinf	5.761 ± 1.916 hr·ng/mL
AUCextrap	10.26% ± 5.66%
Geometric mean ln(Cmax)	About 0.7865 ng/mL
Mean F(AUClast)	0.721 ± 0.199
Bioavailability	About 71% ± 16%
Mean F based on AUCinf	0.756 ± 0.212

The dependent claims also require dose proportionality for Cmax or AUC across selected strengths. A competing product could therefore avoid some dependent claims by producing materially nonproportional exposure, but it would still need to avoid the broader composition and delivery requirements in claim 1.

What pharmacokinetic profile is claimed?

The patent does not protect only a chemical recipe. It also claims the biological performance of the formulation in humans.

The claimed profile includes:

• Mean Tmax of approximately 5 to 120 minutes under claim 20.
• Specific mean Tmax values ranging from approximately 0.97 to 1.12 hours for 100- to 800-microgram doses under claim 7.
• Approximately 60% of mean Cmax within 10 minutes.
• Approximately 86% of mean Cmax by 20 minutes.
• Plasma concentrations above 80% of mean Cmax for approximately two hours.
• Mean time to fentanyl LLOQ of approximately five minutes.
• Substantially dose-proportional Cmax and AUClast.

These limitations create two enforcement consequences. First, a product can fall within the chemical composition range but avoid a dependent claim if its clinical PK profile falls outside the stated parameters. Second, a product that uses a different excipient ratio may avoid literal infringement even if it produces similar clinical exposure.

The terms “about” and “substantially dose proportional” will likely require interpretation from the specification, prosecution history, experimental data and ordinary pharmaceutical usage. They create potential claim-construction disputes because the claims do not state a single numerical tolerance for every “about” limitation.

What is the scope of the formulation claims?

Fentanyl active ingredient

Claim 1 covers fentanyl in free-base form or as a pharmaceutically acceptable salt. The dependent claims also use “derivative,” which broadens the text but may be constrained by the specification and written-description support.

The claims are not expressly limited to fentanyl citrate. A product using another pharmaceutically acceptable fentanyl salt could remain within the claim if it meets the remaining limitations.

Ethanol and propylene glycol

The required solvent system is the central chemical limitation:

• Ethanol: about 50% to about 60% by weight.
• Propylene glycol: about 4% to about 6% by weight.

A formulation containing 49% ethanol or 6.5% propylene glycol may present a literal noninfringement position, subject to the construction of “about.” Small formulation adjustments could therefore have significant freedom-to-operate value.

Propellant-free delivery

The claims exclude propellant-based aerosol systems. A mechanical pump, metered spray pump or other nonpropellant device can fall within the claims if the formulation and droplet limitations are met.

The patent does not require a particular pump manufacturer, actuator design, container material or metering volume. Device patents covering those components would need to be analyzed separately.

Droplet size

The mean droplet diameter must be at least about 10 microns. This limitation distinguishes the claimed delivery from some inhalation or fine-aerosol systems.

Droplet size is a measurable physical property. In an infringement dispute, the result may depend on:

• Measurement method.
• Spray distance.
• Actuator and nozzle configuration.
• Dose volume.
• Temperature and viscosity.
• Whether the measurement is made at the nozzle or at the target surface.
• Whether “mean” refers to arithmetic, volume-weighted or mass-weighted diameter.

A product dossier should preserve validated droplet-size data because this limitation is more objectively testable than the pharmacokinetic terms.

Which claims are most commercially important?

Claims 1 and 21 have the highest commercial value because they are independent and cover the core formulation concept.

Claims 2 and 3 are useful concentration claims. Claims 4 through 15 and 17 through 20 are narrower PK claims that may apply to a marketed product only after human pharmacokinetic testing.

The strongest practical claim combination is likely:

1. Claim 1 for the base formulation and delivery profile.
2. Claim 2 or 3 for the fentanyl concentration.
3. Claim 7 for dose-specific Tmax.
4. Claim 8 or 9 for rapid absorption and sustained plasma concentration.
5. Claim 21 for the five-minute LLOQ and approximately 10-minute 60%-of-maximum limitation.

The PK claims may be difficult to assess before clinical or bioequivalence testing. They also provide potential litigation leverage because a generic or follow-on product may not be able to determine its exact exposure profile solely from the public label.

What is the relationship to Subsys and FDA regulation?

The claim set is directed to the same general product category as Subsys, a fentanyl sublingual spray approved by the FDA for breakthrough pain in opioid-tolerant adults with cancer. Subsys was approved under NDA 203496 and was subject to the FDA’s Transmucosal Immediate Release Fentanyl Risk Evaluation and Mitigation Strategy, commonly known as the TIRF REMS.[1][2]

The patent claims are broader than the approved indication in one respect and narrower in another:

• Broader: Claim 1 refers generally to treatment of pain rather than limiting use to breakthrough cancer pain in opioid-tolerant patients.
• Narrower: The formulation must meet the specified ethanol, propylene glycol, droplet-size and PK limitations.

FDA approval does not establish patent infringement. Conversely, a product can require FDA approval and still avoid this patent through a different formulation or delivery system.

What is the Orange Book status of US Patent 9,642,844?

The Orange Book status must be distinguished from the patent’s substantive scope. FDA Orange Book listing depends on sponsor certification, NDA relevance and the patent information submitted for the approved drug.[3]

For a listed patent, an abbreviated new drug application may address the patent through:

• Paragraph I certification, where no patent information is listed.
• Paragraph II certification, where the patent has expired.
• Paragraph III certification, where the applicant will wait until patent expiration.
• Paragraph IV certification, alleging that the patent is invalid, unenforceable or will not be infringed.

The patent claims supplied here do not establish whether US 9,642,844 is currently listed in the Orange Book, whether it has been delisted, or whether a specific ANDA applicant has filed a Paragraph IV certification. Those matters are regulatory-record issues separate from the patent document.

The relevant commercial question is whether the patent is listed against the approved fentanyl sublingual spray product and whether an ANDA applicant has triggered the Hatch-Waxman litigation framework. FDA’s Orange Book and patent-listing records control that determination.[3][4]

When does US Patent 9,642,844 lose exclusivity?

The patent issued on May 9, 2017. Its nominal US patent term is generally measured from the earliest effective nonprovisional or international filing date, not from the issue date.[5]

Public bibliographic records associate the patent family with a 2011 priority date. On that basis, the nominal term would be expected to extend into approximately 2032, subject to:

• Patent-term adjustment.
• Patent-term extension.
• Terminal disclaimer.
• Earlier disclaimer or lapse.
• Any post-grant cancellation or claim amendment.
• Patent-specific USPTO term calculations.

The issue date alone does not determine expiration. The enforceable expiration date should be taken from the USPTO patent-term record and any applicable Orange Book patent-term information.

What Paragraph IV and generic-entry risks exist?

A generic applicant seeking approval for a fentanyl sublingual spray could challenge the patent in several ways.

Formulation design-around

The most direct strategy is to move outside one or more composition ranges:

• Ethanol below or above the claimed range.
• Propylene glycol below or above the claimed range.
• Alternative cosolvents.
• A different fentanyl concentration.
• A propellant-based or other nonclaimed delivery system.

This approach may avoid literal infringement but could create separate bioequivalence, stability or device-development problems.

PK-based challenge

A product could have similar composition but fail one or more claimed PK limitations. That strategy is less predictable because the independent claims themselves include pharmacokinetic requirements. If the product inherently produces the claimed human PK profile, a formulation change may not avoid infringement merely because the sponsor does not include those PK values in its label.

Droplet-size design-around

A spray with a mean droplet diameter materially below 10 microns could avoid the droplet limitation. That change may affect sublingual deposition, swallowing, systemic exposure and local tolerability.

Invalidity positions

Potential validity issues include:

• Indefiniteness involving “about.”
• Indefiniteness involving “substantially dose proportional.”
• Lack of written description for the full combination of composition and PK outcomes.
• Enablement across the full concentration and excipient ranges.
• Anticipation by earlier fentanyl sprays or transmucosal formulations.
• Obviousness based on known fentanyl delivery systems, ethanol solvents, propylene glycol and conventional spray devices.
• Lack of patentable distinction where the PK profile is an inherent result of an otherwise known formulation.

The strength of these arguments depends on the prosecution history, cited prior art, experimental examples and claim amendments. The supplied claims alone do not resolve validity.

What patent litigation and settlement issues affect the patent?

The patent document contains no information about Paragraph IV notices, ANDA litigation, settlements or licenses. Those events do not arise from the claim language and must be established from court dockets, FDA records, SEC filings or transaction disclosures.

For commercial diligence, the relevant litigation questions are:

Issue	Business impact
Paragraph IV notice	May trigger a 45-day period for filing patent litigation
ANDA litigation	Can impose a 30-month FDA approval stay under Hatch-Waxman
Settlement agreement	May establish an agreed generic-entry date or license terms
Patent listing	Determines whether the patent can support a statutory ANDA challenge
Claim construction	Defines the meaning of “about,” “mean,” and “substantially dose proportional”
Injunction or damages	Determines launch exposure and historical liability

No license or settlement right is apparent from the claim text. The patent should therefore be treated as a formulation right, not as evidence of a broader commercial license or freedom to operate.

How strong is the patent estate for fentanyl sublingual spray?

US 9,642,844 is technically focused rather than comprehensive. Its principal strengths are:

• Combination of composition, spray and PK limitations.
• Coverage of multiple fentanyl dose strengths.
• Protection of rapid absorption characteristics.
• Coverage that is not limited to a single fentanyl salt.
• Independent claim 21 with separate early-exposure requirements.

Its principal limitations are:

• Narrow ethanol and propylene glycol ranges.
• Dependence on human PK results for many claims.
• No express protection for a particular device architecture.
• No standalone manufacturing-process claim in the supplied claims.
• No express method-of-use claim limited to a specific patient population.
• Potential disputes over “about” and “substantially dose proportional.”
• Potential design-around through solvent ratios, droplet size or alternative delivery technology.

The patent is strongest against a close formulation copy. It is weaker as a barrier to all fentanyl transmucosal products, buccal films, sublingual tablets, lozenges, nasal sprays or mechanically distinct delivery systems.

How does US 9,642,844 compare with competing fentanyl delivery technologies?

Technology	Relevance to US 9,642,844	Principal differentiation
Sublingual spray	Directly relevant	Same route and potentially same formulation profile
Sublingual tablet	Usually outside the spray and droplet limitations	Solid dosage form
Buccal film	Usually outside the spray limitation	Mucoadhesive film and buccal delivery
Oral transmucosal lozenge	Usually outside the spray limitation	Solid lozenge with different dissolution profile
Intranasal spray	Outside the sublingual limitation	Nasal deposition and different PK target
Injectable fentanyl	Outside the formulation and route limitations	Parenteral administration
Liposomal or modified-release fentanyl	Potentially outside rapid-absorption limitations	Altered release and exposure profile

A competitor using another dosage form may still face separate patents covering fentanyl, abuse-deterrent technology, packaging, dosing control or clinical use.

Key Takeaways

• US 9,642,844 is a formulation and pharmacokinetic patent for propellant-free fentanyl sublingual spray.
• Claim 1 requires approximately 0.1% to 0.8% fentanyl, 50% to 60% ethanol, 4% to 6% propylene glycol and droplets averaging at least about 10 microns.
• Claim 21 adds approximately 10-minute attainment of 60% maximum plasma concentration and a five-minute LLOQ time.
• The patent covers fentanyl free base and pharmaceutically acceptable salts, not only fentanyl citrate.
• The 400-microgram dose and its Cmax and AUC values are central reference points in the dependent claims.
• The main design-around routes are altered ethanol or propylene glycol levels, different delivery systems, smaller droplets or materially different PK performance.
• The patent’s nominal term is expected to extend into approximately 2032 based on the associated 2011 priority timeline, subject to USPTO term adjustment and patent-specific events.
• Orange Book listing, Paragraph IV activity, litigation and settlements cannot be determined from the claim text itself.
• The patent is a focused barrier to close copies of the claimed spray formulation, not a complete blocking patent for all fentanyl transmucosal products.

FAQs

Does US 9,642,844 cover fentanyl citrate specifically?

Yes, if fentanyl citrate qualifies as the claimed pharmaceutically acceptable salt and the formulation satisfies the remaining composition, spray, droplet and PK limitations. The claim is not limited to fentanyl citrate.

Can a fentanyl sublingual spray avoid the patent by removing propylene glycol?

Potentially. Propylene glycol at approximately 4% to 6% by weight is a required limitation of the independent claims. A formulation without propylene glycol may avoid literal infringement, although other patents and the doctrine of equivalents could remain relevant.

Does the patent cover a sublingual fentanyl tablet?

The supplied claims are directed to a spray formulation and require spray droplets. A sublingual tablet ordinarily would not satisfy those limitations.

Is a generic fentanyl spray automatically blocked until 2032?

No. Generic entry depends on Orange Book listing, patent certifications, litigation, validity, infringement and any settlement or license. A generic applicant may also design around the claimed formulation.

Does FDA approval prove that a product infringes US 9,642,844?

No. FDA approval addresses safety, efficacy, quality and regulatory requirements. Patent infringement depends on whether the product and its use meet the enforceable claim limitations.

References

1. U.S. Food and Drug Administration. (2012). Subsys fentanyl sublingual spray prescribing information.
2. U.S. Food and Drug Administration. (2020). Transmucosal immediate release fentanyl products risk evaluation and mitigation strategy.
3. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book.
4. U.S. Food and Drug Administration. (2024). Approved drug product and patent information resources.
5. United States Patent and Trademark Office. (2024). Patent term adjustment and patent term information.
6. U.S. Patent No. 9,642,844. (2017). Fentanyl sublingual spray formulation. United States Patent and Trademark Office.

Drugs Protected by US Patent 9,642,844

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
Btcp Pharma	SUBSYS	fentanyl	SPRAY;SUBLINGUAL	202788-007	Aug 30, 2012		DISCN	Yes	No			Y

International Family Members for US Patent 9,642,844

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
Poland	2180844