Details for Patent: 9,597,288

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Which drugs does patent 9,597,288 protect, and when does it expire?

Patent 9,597,288 protects ONSOLIS and is included in one NDA.

This patent has forty-four patent family members in twenty-four countries.

Summary for Patent: 9,597,288

Title:	Transmucosal delivery devices with enhanced uptake
Abstract:	The present invention provides methods for enhancing transmucosal uptake of a medicament, e.g., fentanyl or buprenorphine, to a subject and related devices. The method includes administering to a subject a transmucosal drug delivery device comprising the medicament. Also provided are devices suitable for transmucosal administration of a medicament to a subject and methods of their administration and use. The devices include a medicament disposed in a mucoadhesive polymeric diffusion environment and a barrier environment.
Inventor(s):	Andrew Finn, Niraj Vasisht
Assignee:	Biodelivery Sciences International Inc
Application Number:	US15/198,961
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 9,597,288
Patent Claim Types: see list of patent claims	Use; Delivery; Device;

US Patent 9,597,288: Fentanyl Buccal Delivery Scope, Claim Construction, and Patent Landscape

US Patent 9,597,288 protects a specific fentanyl buccal delivery architecture rather than fentanyl generally. The core combination is a biodegradable mucoadhesive layer, a pH-controlled polymeric diffusion environment, an adjacent polymeric barrier layer, unidirectional buccal diffusion, rapid delivery within 30 minutes, and minimum bioavailability thresholds. The broadest practical risk is for fentanyl buccal films or multilayer devices that reproduce these structural and performance characteristics.

The patent has three independent claim categories:

Claim	Category	Core subject matter
1	Method of administration	Administering the claimed fentanyl device to oral mucosa
15	Device	Fentanyl buccal device with diffusion and barrier environments
30	Pain-treatment method	Applying the device to the buccal surface with at least 50% direct buccal absorption and at least 70% overall bioavailability

The patent does not read on every fentanyl formulation, oral film, buccal tablet, or transmucosal product. Infringement requires the accused product or method to satisfy the claim limitations, either literally or under the doctrine of equivalents.

What does US Patent 9,597,288 protect?

The patent protects a multilayer fentanyl transmucosal device with a defined delivery profile.

The required elements of independent claims 1 and 15 are:

1. Fentanyl.
2. A biodegradable mucoadhesive layer.
3. Fentanyl disposed in a polymeric diffusion environment.
4. A diffusion-environment pH between approximately 6 and 8.5.
5. A polymeric barrier environment adjacent to the mucoadhesive layer.
6. A unidirectional fentanyl diffusion gradient when applied to a buccal surface.
7. Overall fentanyl bioavailability of at least approximately 60%.
8. Fentanyl delivery in less than approximately 30 minutes.

Claim 30 is narrower. It requires:

• A method for treating pain.
• Adhesion to a buccal surface.
• A pH-buffered diffusion environment between approximately 6 and 8.5.
• At least approximately 50% direct buccal absorption.
• At least approximately 70% overall bioavailability.
• Delivery in less than approximately 30 minutes.

The claims therefore combine composition, device architecture, route of administration, pharmacokinetics, and therapeutic use.

How do the independent claims differ?

Claim 1: administration method

Claim 1 requires a human administration step. A product manufacturer could face method-claim exposure if the product is intentionally supplied or promoted for use in a manner that meets every limitation.

The claim is not limited to pain treatment. It requires delivery of fentanyl to a human, but it does not expressly require a particular pain indication. The device and performance requirements remain mandatory.

Claim 15: device claim

Claim 15 is directed to the device itself. It does not require the preamble's "method for delivering" steps, but it incorporates functional limitations concerning application to a buccal surface, bioavailability, and delivery time.

A device claim can create a stronger commercial enforcement position than a pure method claim because manufacture, sale, and importation of the device may be actionable under 35 U.S.C. § 271(a), depending on the claim construction and accused product.

Claim 30: pain-treatment method

Claim 30 is the narrowest independent claim. It adds the requirement that at least 50% of fentanyl transmucosal delivery occur by direct buccal absorption and raises the overall bioavailability threshold to at least 70%.

This claim creates a substantial evidentiary burden. The patent owner would need to establish not only the device's structure but also the relevant absorption and pharmacokinetic performance.

What are the key limitations in the patent claims?

Polymeric diffusion environment

The diffusion environment is the fentanyl-containing portion of the device. Claims 3, 11, 17, and 25 narrow this limitation by requiring:

• At least one film-forming water-erodible adhesive polymer; and
• At least one bioadhesive polymer.

The independent claims do not expressly require both polymer types. A formulation containing a different polymer system may avoid these dependent claims while still potentially implicating claims 1, 15, or 30.

pH range and buffering

The independent claims require a pH between approximately 6 and 8.5. Claims 5, 9, 19, and 23 narrow the range to approximately 7 to 7.5.

Claims 8, 9, 22, and 23 require that the environment be buffered. The distinction matters:

Claim scope	pH requirement
Claims 1 and 15	pH between approximately 6 and 8.5
Claims 5 and 19	pH between approximately 7 and 7.5
Claims 8 and 22	Buffered to approximately 6 to 8.5
Claims 9 and 23	Buffered to approximately 7 to 7.5

The claim language may create disputes over whether pH is measured during manufacture, before administration, after hydration, or during dissolution in the oral cavity. The patent specification and prosecution history would control the construction of those terms. For freedom-to-operate purposes, a product tested outside the claimed pH range at the legally relevant measurement point could avoid literal infringement, but formulation changes must also be evaluated against the remaining limitations.

Polymeric barrier environment

The barrier environment is disposed adjacent to the fentanyl-containing mucoadhesive layer. The claims are directed to a barrier that supports unidirectional diffusion toward the buccal mucosa.

Claims 4, 12, 18, and 26 narrow the barrier to at least one film-forming water-erodible polymer. The independent claims do not require that specific polymer class.

A conventional bilayer film may present greater literal-infringement risk than a single-layer film because the adjacent barrier and directional diffusion limitations are central to the claimed architecture.

Unidirectional diffusion

The claims require a unidirectional diffusion gradient upon application to a buccal surface. This limitation distinguishes the claimed device from dosage forms that release fentanyl substantially in multiple directions or primarily dissolve in saliva before absorption.

Evidence relevant to this limitation may include:

• Cross-sectional device design.
• Polymer-layer composition.
• In vitro directional release data.
• Permeation-cell testing.
• Surface coating or barrier characterization.
• Product instructions requiring placement against the cheek.

Bioavailability and delivery time

The independent claims require both a pharmacokinetic threshold and a delivery-time threshold:

Requirement	Claims
At least 60% overall bioavailability	1 and 15
At least 70% overall bioavailability	2, 10, 16, 24, and 30
Less than 30-minute delivery	1, 15, and 30
At least 50% direct buccal absorption	30

"Overall bioavailability" is broader than direct buccal absorption. Claim 30 separately requires at least 50% direct buccal absorption and at least 70% overall bioavailability. A product can therefore satisfy the overall bioavailability requirement while failing the direct-buccal-absorption limitation if a substantial portion of fentanyl is absorbed after swallowing.

These parameters are potentially vulnerable to disputes involving:

• Reference formulation.
• Patient population.
• Dose strength.
• Fed or fasted conditions.
• Definition of complete delivery.
• Pharmacokinetic assay.
• Statistical averaging.
• Measurement of direct buccal versus gastrointestinal absorption.

What do the dependent claims add?

Claims	Added limitation	Commercial significance
2, 10, 16, 24	At least 70% overall bioavailability	Raises performance threshold
3, 11, 17, 25	Film-forming water-erodible adhesive polymer plus bioadhesive polymer	Targets common film architecture
4, 12, 18, 26	Film-forming water-erodible barrier polymer	Narrows barrier composition
5, 9, 19, 23	pH approximately 7 to 7.5	Narrows pH window
6, 13, 20, 27	Opioid antagonist	Covers abuse-deterrent or overdose-mitigation formulations
7, 14, 21, 29	Third layer or coating	Covers multilayer or coated devices
8, 9, 22, 23	Buffered pH	Requires buffering rather than an unbuffered pH condition
28	Naloxone as the opioid antagonist	Most specific antagonist claim

Claim 28 is particularly narrow. A formulation containing naloxone must still meet the parent claim's fentanyl, pH, barrier, bioavailability, delivery-time, and buccal-application requirements.

What formulations are most exposed to US 9,597,288?

The highest-risk product profile is a fentanyl buccal film with:

• A fentanyl-containing biodegradable adhesive layer.
• A backing or barrier layer adjacent to the drug layer.
• A neutral or near-neutral buffered pH.
• Demonstrated one-way release toward buccal tissue.
• Delivery in under 30 minutes.
• Bioavailability of at least 60%, or 70% for narrower claims.
• Optional naloxone or another opioid antagonist.

A product with only one or two of these characteristics is not necessarily within the claims. The risk increases when the formulation uses the same combination and achieves the specified performance.

Lower-risk design alternatives

Potential design-around paths may include:

• A non-biodegradable device, if the claim requires biodegradability as construed.
• A dosage form without an adjacent polymeric barrier environment.
• A product that does not provide unidirectional diffusion.
• A pH outside the claimed range.
• A slower-release product exceeding the 30-minute limitation.
• A product with bioavailability below the claimed threshold.
• A dosage form using a tablet, lozenge, spray, or liquid rather than a layered mucoadhesive film.
• A formulation in which fentanyl is not disposed in the claimed polymeric diffusion environment.

Each route carries technical and regulatory tradeoffs. Altering pH, absorption, residence time, or release rate can affect product performance and FDA comparability requirements.

How does the patent compare with competing fentanyl products?

US 9,597,288 is directed to buccal film technology. It is less relevant to products using other routes or dosage forms.

Product or technology	Route	Likely relevance to US 9,597,288
Onsolis	Buccal soluble film	Highest conceptual overlap
Fentora	Buccal tablet	Route overlap, but different device architecture
Actiq	Oral transmucosal lozenge	Fentanyl and transmucosal overlap, limited structural overlap
Abstral	Sublingual tablet	Limited overlap unless buccal use and claimed architecture are present
Subsys	Sublingual spray	Generally outside the claimed layered-device architecture
Lazanda	Intranasal spray	Outside the buccal-device claims
Injectable fentanyl	Parenteral	Outside the claims

The closest commercial technology is a fentanyl buccal soluble film such as Onsolis. A buccal tablet may practice some functional concepts but ordinarily would not meet a claim requiring a biodegradable mucoadhesive layer and adjacent polymeric barrier environment unless its construction and performance satisfy those limitations.

What is the relationship to Onsolis and BEMA technology?

Onsolis was FDA-approved as a fentanyl buccal soluble film for breakthrough cancer pain in opioid-tolerant adults. The product used BioErodible MucoAdhesive, or BEMA, technology associated with BioDelivery Sciences International. FDA approved Onsolis in 2009 under NDA 022567 and imposed a risk evaluation and mitigation strategy because of fentanyl's serious safety risks.[2]

The claims of US 9,597,288 align closely with the technical attributes associated with BEMA-style products:

• Mucoadhesion to the buccal mucosa.
• A drug-containing polymeric layer.
• A backing or barrier layer.
• Directional delivery.
• Rapid transmucosal absorption.
• High fentanyl bioavailability.

The patent should not be treated as covering every BEMA product. Claim coverage turns on the specific fentanyl formulation, pH, polymer arrangement, and performance limitations.

What is the Orange Book status of US 9,597,288?

FDA Orange Book relevance depends on whether the patent was submitted for listing against an approved product and whether FDA accepted the submission under its listing standards. Product-patent listing and method-of-use listing are separate issues.

For a fentanyl buccal product, relevant regulatory records include:

• NDA 022567 for Onsolis.
• FDA Orange Book patent listings.
• FDA-approved labeling.
• Any associated pediatric-exclusivity or regulatory-exclusivity entries.
• NDA supplements affecting formulation or delivery.

A patent may be legally enforceable even if it is not listed in the Orange Book. Conversely, Orange Book listing does not establish infringement or patent validity. It mainly affects the Hatch-Waxman notice-and-stay framework for an ANDA applicant.

A Paragraph IV certification against a listed patent could trigger notice obligations and, if suit is filed within the statutory period, a potential 30-month stay of ANDA approval under 21 U.S.C. § 355(j)(5)(B)(iii). A patent covering a method of use may raise separate section viii carve-out issues, while a device or formulation claim is more likely to require a Paragraph IV certification if listed against the drug product.

When does US 9,597,288 lose exclusivity?

The patent issued on March 21, 2017. Its expiration date depends on the earliest effective nonprovisional filing date, patent-term adjustment, terminal disclaimers, and any applicable patent-term extension.

The ordinary term for a modern US utility patent is 20 years from the earliest effective nonprovisional filing date, subject to statutory adjustments under 35 U.S.C. §§ 154 and 156. The issue date alone does not establish the expiration date.

The principal expiration analysis should account for:

Term factor	Effect
Earliest priority filing	Establishes the starting point for the 20-year term
Patent-term adjustment	Can extend the term for USPTO delay
Terminal disclaimer	Can limit the term to another patent's expiration
Patent-term extension	May apply for qualifying FDA regulatory delay
Patent-term adjustment disclaimer	Can reduce available term
Continuation status	Usually preserves the earlier effective filing date

No reliable commercial exclusivity conclusion should be drawn from the 2017 issue date alone. Patent expiration and FDA regulatory exclusivity are separate. A patent may remain enforceable after FDA exclusivity ends, and a product may face generic competition after patent expiry if regulatory requirements are satisfied.

Which companies could challenge the patent?

Potential challengers would include:

• Generic manufacturers seeking an ANDA for a fentanyl buccal film.
• Specialty opioid companies developing buccal or transmucosal fentanyl products.
• Companies developing abuse-deterrent fentanyl products containing naloxone.
• 505(b)(2) sponsors seeking approval for a modified buccal fentanyl formulation.
• Manufacturers of alternative films using different polymers, pH systems, or release profiles.

A generic or 505(b)(2) applicant would likely evaluate:

1. Orange Book listings.
2. Paragraph IV exposure.
3. Claim construction.
4. Anticipation and obviousness based on earlier buccal films.
5. Enablement and written-description support for the bioavailability limitations.
6. Definiteness of "unidirectional diffusion gradient."
7. Reproducibility of the direct-buccal-absorption limitation.
8. Whether the commercial product actually satisfies the claimed performance thresholds.

What prior-art issues affect patent strength?

The strongest validity challenge would likely focus on the combination of known elements:

• Fentanyl transmucosal delivery.
• Mucoadhesive oral films.
• Water-erodible polymers.
• Backing layers.
• pH adjustment.
• Directional drug release.
• Rapid opioid absorption.

The patent's potential strength comes from the claimed combination and performance profile rather than from fentanyl, mucoadhesion, or buccal administration individually.

Potential anticipation arguments

An anticipation reference would need to disclose every limitation in a single prior-art reference, including:

• The claimed pH range.
• The polymeric diffusion environment.
• The adjacent barrier environment.
• Unidirectional buccal diffusion.
• The bioavailability threshold.
• Delivery in less than 30 minutes.

A reference describing a fentanyl buccal film but lacking measured bioavailability or the specified pH may not anticipate the claims.

Potential obviousness arguments

An obviousness challenge could combine references concerning:

• Fentanyl buccal delivery.
• Mucoadhesive films.
• Backing layers.
• pH buffering.
• Enhanced buccal absorption.

The patent owner would likely rely on the claimed combination's pharmacokinetic performance, directional delivery, and formulation interaction. Objective evidence, including unexpected bioavailability, commercial success, or long-felt need, could affect the analysis if properly tied to the claimed features.

What litigation and settlement issues matter?

The most important litigation questions are:

• Whether US 9,597,288 was listed for the relevant NDA.
• Whether an ANDA or 505(b)(2) applicant filed a Paragraph IV certification.
• Whether the patent owner sued within 45 days of receiving notice.
• Whether a 30-month stay applied.
• Whether the parties entered a settlement allowing a licensed or date-certain generic launch.
• Whether the settlement was reported under the Federal Trade Commission's pharmaceutical agreement reporting requirements.
• Whether later litigation involved patent misuse, antitrust claims, or reverse-payment allegations.

A settlement can preserve patent exclusivity without producing a published merits decision. The absence of a reported infringement judgment does not establish that the patent is weak or irrelevant.

How strong is the patent estate for fentanyl buccal delivery?

US 9,597,288 is strongest against products that replicate the entire BEMA-type configuration and achieve the claimed pharmacokinetic results. Its principal weaknesses are the number of measurable functional limitations and the technical disputes surrounding them.

Factor	Assessment
Structural specificity	Moderate to high
Functional limitations	High
Design-around potential	Moderate
Relevance to buccal films	High
Relevance to tablets and sprays	Low to moderate
Proof burden in litigation	High
Potential prior-art exposure	Material
Importance of prosecution history	High
Importance of formulation testing	High

Claims 1 and 15 provide the principal commercial coverage. Claim 30 may provide meaningful additional protection for products with proven high direct-buccal absorption, but it is more demanding to enforce because absorption pathways and bioavailability must be established.

What generic launch scenarios exist?

Scenario 1: No listed-patent barrier

If no relevant patent is listed, an ANDA applicant may avoid the Orange Book 30-month stay mechanism. The applicant would still need to address non-listed patents through ordinary infringement-risk analysis.

Scenario 2: Paragraph IV challenge

A generic applicant may certify that the listed patent is invalid, unenforceable, or not infringed. The patent owner may sue, creating a potential 30-month approval stay.

Scenario 3: Section viii carve-out

A carve-out may be possible for a method-of-use patent, but it is less useful where the listed claims cover the device or formulation itself.

Scenario 4: Design-around product

A manufacturer may pursue a buccal or transmucosal fentanyl product that changes the polymer system, release direction, pH, dosage form, or bioavailability profile. That strategy may reduce patent risk but can create new clinical, CMC, and regulatory requirements.

Scenario 5: 505(b)(2) launch

A 505(b)(2) applicant may use existing fentanyl safety and efficacy information while developing a modified delivery system. Patent certification and labeling obligations would depend on the listed patents and proposed labeling.

What geographic coverage does the patent provide?

US 9,597,288 provides protection only in the United States. It does not establish protection in Europe, Canada, Japan, or other markets.

International protection must be evaluated through the corresponding patent family. Key jurisdictional issues include:

• Whether counterpart applications issued.
• Whether claims were narrowed during prosecution.
• Whether national patents remain in force.
• Whether supplementary protection or regulatory extensions apply.
• Whether local claim constructions differ.
• Whether the relevant product was approved in the jurisdiction.

A US-only freedom-to-operate conclusion cannot be extended to international markets.

What manufacturing and IP barriers remain after patent expiry?

Patent expiry would not eliminate all launch barriers. A competing manufacturer may still need to resolve:

• Fentanyl controlled-substance registration and security.
• DEA manufacturing and distribution requirements.
• FDA CMC requirements for multilayer films.
• Content uniformity at low fentanyl loadings.
• Adhesion and residence-time reproducibility.
• Moisture sensitivity and packaging.
• Abuse-deterrence or overdose-mitigation features.
• Bioequivalence for a complex locally acting transmucosal product.
• REMS or other opioid-risk controls.
• Trade secrets covering polymer processing, coating, drying, and converting.

Manufacturing know-how may remain commercially relevant even when the patent claims expire.

Key Takeaways

• US 9,597,288 covers a fentanyl buccal delivery system combining a biodegradable mucoadhesive layer, pH-controlled diffusion environment, adjacent polymeric barrier, unidirectional release, rapid delivery, and minimum bioavailability.
• Claims 1 and 15 are the principal broad claims. Claim 30 is narrower but adds direct-buccal-absorption requirements.
• The closest commercial technology is a fentanyl buccal soluble film, particularly a BEMA-type product such as Onsolis.
• Fentora, Actiq, Abstral, Subsys, Lazanda, and injectable fentanyl products generally present lower structural overlap because they use different dosage forms or routes.
• The most important infringement questions concern the polymeric barrier, pH measurement, unidirectional diffusion, delivery time, and bioavailability testing.
• The patent's enforceability and commercial value depend heavily on its priority chain, terminal disclaimers, patent-term adjustment, Orange Book listing, and any Paragraph IV litigation.
• Patent expiry must be determined from the effective filing date and term adjustments, not from the March 21, 2017 issue date.
• A generic launch could proceed through a Paragraph IV challenge, a section viii carve-out where available, a design-around formulation, or a 505(b)(2) pathway.
• Patent expiry would not remove fentanyl-specific regulatory, manufacturing, controlled-substance, and bioequivalence barriers.

FAQs

Does US 9,597,288 cover all fentanyl buccal films?

No. The product must satisfy the claimed structural and functional limitations, including the biodegradable mucoadhesive layer, polymeric diffusion environment, adjacent barrier environment, buccal directional diffusion, pH range, delivery time, and bioavailability threshold.

Does adding naloxone automatically create infringement?

No. Naloxone is required only by dependent claims 6, 13, 20, 27, and 28. A naloxone-containing product must also satisfy the parent claim's fentanyl device, pH, barrier, diffusion, delivery-time, and bioavailability limitations.

Can a buccal tablet infringe US 9,597,288?

Potentially, but only if the tablet has the claimed biodegradable mucoadhesive and adjacent polymeric barrier architecture and meets the functional limitations. Route of administration alone is insufficient.

Is a product with 60% bioavailability within the 70% claims?

No. It may fall within claims requiring at least 60% bioavailability if all other limitations are met, but it would not satisfy claims requiring at least 70% bioavailability.

Does an FDA-approved fentanyl product automatically practice the patent?

No. FDA approval does not establish patent infringement. The product must be compared limitation by limitation against the issued claims, and the relevant patent status must be evaluated separately from regulatory approval.

References

1. United States Patent and Trademark Office. (2017). U.S. Patent No. 9,597,288, Fentanyl buccal delivery device and methods of use.
2. U.S. Food and Drug Administration. (2009). FDA approves Onsolis for breakthrough cancer pain in opioid-tolerant adults.
3. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations.
4. United States Code, 21 U.S.C. § 355.
5. United States Code, 35 U.S.C. §§ 154, 156, 271.
6. U.S. Food and Drug Administration. (2024). Orange Book: Approved drug products with therapeutic equivalence evaluations.

Drugs Protected by US Patent 9,597,288

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Adalvo	ONSOLIS	fentanyl citrate	FILM;BUCCAL	022266-001	Jul 16, 2009		DISCN	No	No	9,597,288		Y			MANAGEMENT OF BREAKTHROUGH PAIN IN PATIENTS WITH CANCER
Adalvo	ONSOLIS	fentanyl citrate	FILM;BUCCAL	022266-002	Jul 16, 2009		DISCN	No	No	9,597,288		Y			MANAGEMENT OF BREAKTHROUGH PAIN IN PATIENTS WITH CANCER
Adalvo	ONSOLIS	fentanyl citrate	FILM;BUCCAL	022266-003	Jul 16, 2009		DISCN	No	No	9,597,288		Y			MANAGEMENT OF BREAKTHROUGH PAIN IN PATIENTS WITH CANCER
Adalvo	ONSOLIS	fentanyl citrate	FILM;BUCCAL	022266-004	Jul 16, 2009		DISCN	No	No	9,597,288		Y			MANAGEMENT OF BREAKTHROUGH PAIN IN PATIENTS WITH CANCER
Adalvo	ONSOLIS	fentanyl citrate	FILM;BUCCAL	022266-005	Jul 16, 2009		DISCN	No	No	9,597,288		Y			MANAGEMENT OF BREAKTHROUGH PAIN IN PATIENTS WITH CANCER

International Family Members for US Patent 9,597,288

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2007275581
Brazil	122020000250
Brazil	PI0714712
Canada	2658585
China	101511337