# United States Patent 10,245,228: Sufentanil Oral Transmucosal Dosage-Form Claims and Patent Landscape

US Patent 10,245,228 covers small, bioadhesive oral-transmucosal dosage forms containing sufentanil, including sufentanil citrate. Its principal commercial relevance is to sublingual sufentanil products such as DSUVIA. The patent does not claim sufentanil as a molecule, sufentanil citrate generally, or every sublingual sufentanil formulation. It claims a defined combination of dose, physical size, bioadhesion, administration route, and pharmacokinetic performance.

The strongest independent product claim is claim 1. The broadest independent method claim is claim 16 because it does not require the Tmax variability, Tmax range, Cmax, oral-transmucosal fraction, or bioavailability limitations appearing in several product claims. The patent’s practical scope therefore depends heavily on whether a competing product uses a bioadhesive dosage form within the stated size and dose parameters.

What does US Patent 10,245,228 protect?

US 10,245,228 protects three related categories:

A small bioadhesive dosage form containing 5 to 100 micrograms of sufentanil.
A drug-delivery device containing that dosage form.
A method of treating pain by administering that dosage form to the oral mucosa.

The core claim elements are:

Element	Claim 1 requirement
Active ingredient	Sufentanil
Dose	5.0 to 100 micrograms
Administration	Oral transmucosal
Adhesion	Bioadhesive
Physical size	Volume below 30 microliters or mass below 30 mg
Pharmacokinetics	Tmax coefficient of variation below 40%

Claim 16 contains a similar dosage-form and treatment combination but omits the Tmax variability limitation from the independent claim. That distinction materially broadens the method claim.

What drug products are technically relevant?

A product is potentially relevant if it is:

A tablet, film, pellet, wafer, insert, or other oral dosage form;
Intended for sublingual, buccal, or another oral-mucosal site;
Bioadhesive;
Within the claimed dose range;
Below either the claimed volume or mass threshold; and
Used to deliver sufentanil for pain treatment.

The claims are not limited to a particular excipient, polymer, manufacturing process, tablet shape, compression force, dissolution time, or packaging system. The absence of a formulation-specific polymer limitation gives the claims broader formulation coverage than a claim directed only to a particular matrix or adhesive composition.

How should the independent claims be construed?

Claim 1: product claim

Claim 1 requires every listed feature. A product containing 30 micrograms of sufentanil may fall within the dose range, but dose alone is insufficient. The product must also satisfy the bioadhesive, size, route, and Tmax coefficient-of-variation limitations.

The phrase “less than 30 microliters or a mass of less than 30 mg” creates alternative size tests. A product can satisfy the limitation by meeting either one:

Volume below 30 microliters; or
Mass below 30 mg.

The same alternative structure applies to claim 2, which narrows the threshold to below 10 microliters or below 10 mg.

A product weighing 12 mg but having a volume of 12 microliters would satisfy claim 1 and claim 2, assuming the other limitations are met. A product weighing 35 mg and having a volume of 35 microliters would not satisfy the size limitation.

Claim 16: method-of-treatment claim

Claim 16 requires:

Administration to the oral mucosa;
A bioadhesive dosage form;
5 to 100 micrograms of sufentanil; and
A volume below 30 microliters or mass below 30 mg.

Unlike claim 1, claim 16 does not independently require a Tmax coefficient of variation below 40%. Claims 18 through 22 add pharmacokinetic or oral-transmucosal delivery limitations, but a method falling within claim 16 may be actionable without satisfying those dependent-claim features.

This structure makes claim 16 important in competitive analysis. A generic or follow-on product could avoid claims 1 and 18 by failing to demonstrate the specified Tmax variability while still presenting risk under claim 16.

What narrower limitations are added by claims 2 through 15?

Claims	Limitation	Commercial significance
2	Below 10 microliters or below 10 mg	Targets highly compact dosage forms
3-5	At least 50%, 55%, or 60% of delivery through oral transmucosal route	Addresses swallowed-drug contribution
6	Tmax of about 19.8 to 60 minutes	Defines an absorption-speed range
7	Dose-normalized Cmax of about 2.72 ± 0.84 pg/mL per microgram	Claims a specific exposure profile
8	Combined Tmax and Cmax limitations	More technically narrow but potentially stronger if reproducibly demonstrated
9	Sublingual administration	Directly relevant to sublingual tablets
10	Buccal administration	Covers a separate oral-mucosal site
11-13	Bioavailability above 65%, 75%, or 80%	Adds systemic exposure thresholds
14	Sufentanil citrate	Narrows the active ingredient to a salt form
15	Drug-delivery device containing claim 1 dosage form	Extends claim coverage to an applicator or delivery system

Claims 6 through 13 are performance claims. They may be difficult to assess from product specifications alone because infringement analysis would require pharmacokinetic data, clinical testing, or reliable comparative evidence.

What formulations are protected by US 10,245,228?

The patent claims a formulation by functional and physical attributes rather than by a named excipient system. Potentially covered formats include:

Sublingual tablets;
Buccal tablets;
Bioadhesive films;
Mucoadhesive wafers;
Small oral inserts;
Compressed or molded dosage forms; and
Drug-delivery devices containing one of those forms.

The patent’s formulation boundary is therefore defined by the claimed result and configuration. A formulation may be within scope even if it uses different excipients from the commercial reference product, provided it remains bioadhesive, contains the claimed sufentanil dose, meets the size limitation, and satisfies any applicable dependent-claim performance requirement.

The patent does not, based on the quoted claims, require:

A specific polymer;
A particular tablet hardness;
A specified dissolution profile;
A particular pH;
A particular manufacturing method;
A specific applicator design; or
A particular indication beyond pain treatment in the method claims.

How strong is the patent estate for sublingual sufentanil?

US 10,245,228 is one component of a broader AcelRx sufentanil patent estate. The estate has historically been directed to different layers of the DSUVIA product architecture:

Protection layer	Typical subject matter
Active formulation	Sufentanil dosage forms and salt forms
Route and delivery	Sublingual or oral-transmucosal administration
Performance	Tmax, Cmax, bioavailability, and transmucosal delivery fraction
Physical design	Small dosage-form dimensions and mass
Device	Applicators and drug-delivery devices
Manufacturing	Production and handling of low-dose opioid dosage forms
Clinical use	Treatment of acute pain in monitored settings

The estate is stronger when these layers are read together. A competitor that avoids one patent by changing an excipient may still face claims directed to the device, route, pharmacokinetic profile, or manufacturing process.

The vulnerability of US 10,245,228 is that several limitations are functional or performance-based. A challenger may contest:

Whether the dosage form is legally “bioadhesive”;
How the volume or mass is measured;
Whether the stated Tmax coefficient of variation is an inherent product property;
Whether the claimed pharmacokinetic results are sufficiently enabled across the full 5-to-100-microgram range;
Whether the claims improperly rely on post-administration clinical results; and
Whether the claims are anticipated by earlier oral-transmucosal sufentanil disclosures.

When does US 10,245,228 lose patent protection?

The patent issued on April 2, 2019. Its expiration date is governed by the earliest effective nonprovisional priority date, any patent-term adjustment, and any terminal disclaimer. A 20-year calculation from the earliest priority date places the family’s ordinary expiration around 2030, subject to the official USPTO term calculation.

The commercially relevant loss-of-exclusivity timeline has several separate components:

Exclusivity type	Relevance
New chemical entity exclusivity	Sufentanil is an old active ingredient, so NCE exclusivity is not the principal DSUVIA barrier
New drug exclusivity	FDA approval of DSUVIA created a regulatory exclusivity period, but it is separate from patent term
Patent term	The relevant composition, delivery, and method patents may extend into approximately 2030 or later depending on family and adjustments
Pediatric exclusivity	Any applicable six-month extension would be added to qualifying FDA exclusivity or patent terms
REMS and controlled-substance controls	These affect commercialization and generic development but do not extend patent term

A product’s commercial launch date cannot be determined from US 10,245,228 alone. Orange Book listings, approved labeling, Paragraph IV certifications, litigation, settlements, and any pediatric extension must be evaluated together.

What is the FDA and Orange Book status of the related product?

DSUVIA is a 30-microgram sublingual tablet containing sufentanil, approved by FDA in November 2018 for the management of acute pain in adults in a certified medically supervised healthcare setting [2]. The product is administered sublingually and is supplied with a disposable applicator system.

FDA approval is relevant to the patent analysis because it confirms the commercial product’s dosage strength, route, and indication. It does not, by itself, establish infringement of every claim in US 10,245,228.

The Orange Book is the controlling source for listed patents and use codes associated with an approved product [3]. Relevant questions include:

Whether US 10,245,228 is currently listed for DSUVIA;
Which claims are identified in the listing;
Whether the listing is directed to the drug product, method of use, or both;
Whether a later applicant must address the patent through certification; and
Whether any delisting or expiration event has occurred.

An ANDA applicant seeking approval before listed patent expiration may file a Paragraph IV certification alleging that the patent is invalid, unenforceable, or not infringed. The patent owner may then bring an action under Hatch-Waxman, potentially triggering a statutory approval stay of up to 30 months, subject to statutory exceptions and court developments [4].

Which companies could challenge the patent?

Potential challengers fall into four groups:

Generic pharmaceutical companies developing sufentanil sublingual tablets.
Specialty companies developing alternative oral-transmucosal opioid products.
Contract manufacturers supplying a competing dosage form.
Innovators developing non-sufentanil acute-pain products that compete commercially without directly practicing the claims.

A generic sufentanil product would face a higher patent risk if it matches the DSUVIA profile: approximately 30 micrograms, a very small sublingual tablet, bioadhesion, rapid absorption, and a dedicated applicator. A product using a larger dosage form, a nonadhesive formulation, a different administration route, or a non-sufentanil active ingredient may reduce literal infringement risk, although doctrine-of-equivalents issues could remain.

What Paragraph IV and litigation risks affect US 10,245,228?

A Paragraph IV case would likely focus on four technical issues.

Anticipation and obviousness

Prior art involving oral-transmucosal sufentanil could be used to challenge the dose range, route, salt, or dosage-form concept. The patent owner would rely on the combination of unusually small size, bioadhesion, consistent Tmax, and high transmucosal delivery.

Written description and enablement

The claims cover 5 to 100 micrograms and multiple performance outcomes. A challenger could argue that the specification does not adequately support the entire breadth of those ranges or enable all claimed formulations without undue experimentation.

Definiteness and measurement methodology

Terms such as “bioadhesive,” “about,” “dose-normalized Cmax,” and “drug delivery” require defined testing conditions. Disputes may concern:

The mucosal model used;
Sampling time points;
The population used to calculate Tmax variability;
The method for measuring swallowed versus transmucosal delivery; and
The meaning of “about” in the claimed pharmacokinetic ranges.

Infringement proof

Claims 6 through 13 require product-performance evidence. A patent owner may need clinical or pharmacokinetic testing of the accused product. Claims 1 and 16 offer a more direct path if the size, dose, bioadhesion, and route can be established from product development documents, labeling, batch records, and physical testing.

No specific Paragraph IV litigation or settlement can be attributed to US 10,245,228 from the claim text alone. Litigation status must be determined from the current FDA Orange Book, USPTO Patent Center, and PACER records.

How does this patent compare with competing pain-drug patent estates?

Product category	Main patent risk	Commercial difference
Sufentanil sublingual tablet	Direct overlap with dose, route, bioadhesion, size, and PK claims	Closest competitor
Buccal sufentanil product	Claims 1 and 10 may be relevant	Route may avoid sublingual-only claims but not oral-transmucosal claims
Intravenous sufentanil	Generally outside the quoted dosage-form claims	Competes clinically but not usually technically
Non-opioid acute-pain product	No sufentanil claim overlap	Regulatory and clinical substitution risk
Larger oral sufentanil dosage form	May avoid size limitations	Could remain exposed if dimensions are reduced or equivalents apply
Nonadhesive transmucosal formulation	Potentially avoids a key element	May sacrifice residence time and delivery consistency

What manufacturing and geographic barriers matter?

The patent is enforceable in the United States only. Foreign family members must be assessed separately by jurisdiction, national-phase status, local claim amendments, maintenance payments, and term adjustments.

Manufacturing risk extends beyond the product claims. A competing manufacturer may need to solve:

Uniform distribution of microgram quantities of sufentanil;
Content uniformity at commercial scale;
Adhesion without excessive mucosal irritation;
Tablet integrity during applicator delivery;
Stability and moisture control;
Controlled-substance security;
Low-dose analytical validation; and
Consistent dissolution and transmucosal absorption.

These manufacturing barriers can delay a generic launch even when a challenger has a noninfringement position.

What generic launch scenarios exist?

At-risk launch before patent expiry

A challenger could launch after a favorable Paragraph IV judgment, settlement license, patent expiration, or successful invalidity challenge. The business risk would include damages, injunction exposure, regulatory disruption, and controlled-substance supply constraints.

Carve-out or limited-label launch

A label carve-out may reduce method-of-use exposure where the patent is listed only for a specific indication or administration method. It would not necessarily avoid product claims covering the dosage form itself.

Design-around launch

A competitor could target a product outside one or more core limitations by using:

A nonbioadhesive dosage form;
A mass or volume above the claimed thresholds;
A non-oral route;
A different active ingredient;
A delivery profile outside the narrower PK claims; or
A dosage form that does not contain sufentanil citrate.

The broadest design-around challenge is claim 16, because changing Tmax performance alone may not avoid the independent method claim.

Key Takeaways

US 10,245,228 protects a small, bioadhesive, oral-transmucosal sufentanil dosage form.
Claim 1 combines a 5-to-100-microgram dose range, size limitation, bioadhesion, oral-transmucosal delivery, and Tmax variability.
Claim 16 is materially broader as an independent method claim because it omits the Tmax variability requirement.
Claims 6 through 13 add pharmacokinetic and bioavailability limitations that may be powerful but require testing-intensive infringement proof.
The patent is directly relevant to DSUVIA-type 30-microgram sublingual sufentanil products.
The broader AcelRx estate likely creates cumulative risk across formulation, device, route, performance, manufacturing, and method-of-use layers.
Patent expiration is expected to fall around the 2030 period based on the family’s priority structure, subject to official term adjustments and any disclaimer.
FDA approval and Orange Book listing determine the regulatory pathway for generic challenges, but they do not independently establish infringement.
A Paragraph IV challenger would likely focus on obviousness, enablement, definiteness, measurement methodology, and the breadth of the 5-to-100-microgram claims.

FAQs About US Patent 10,245,228

Does US 10,245,228 claim DSUVIA by name?

No. The quoted claims do not name DSUVIA. They claim technical characteristics that may read on a DSUVIA-type product, including sufentanil dose, oral-transmucosal administration, bioadhesion, small size, and pharmacokinetic performance.

Does the patent cover all sufentanil tablets?

No. A sufentanil tablet must satisfy the claimed route, bioadhesion, dose, and size requirements, along with any applicable performance limitations.

Can a buccal sufentanil product infringe?

Yes. Claim 10 expressly identifies buccal administration, and the broader oral-transmucosal claims may also be relevant.

Is sufentanil citrate separately protected?

Claim 14 specifically narrows the dosage form to sufentanil citrate. That claim does not prevent all use of sufentanil citrate outside the claimed dosage-form and administration framework.

Can a generic avoid the patent by changing Tmax?

Changing Tmax may avoid claims that require a specific Tmax range or coefficient of variation. It would not necessarily avoid independent claim 16, which does not include those pharmacokinetic limitations.

References

United States Patent and Trademark Office. (2019). U.S. Patent No. 10,245,228, Sufentanil dosage forms.
U.S. Food and Drug Administration. (2018). FDA approves new dosage form of sufentanil for acute pain management.
U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations, Orange Book.
U.S. Food and Drug Administration. (n.d.). Abbreviated new drug application and patent certification requirements.

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Vertical Pharms	DSUVIA	sufentanil citrate	TABLET;SUBLINGUAL	209128-001	Nov 2, 2018		DISCN	Yes	No	⤷ Start Trial	⤷ Start Trial	Y			TREATMENT OF ACUTE PAIN	⤷ Start Trial
>Applicant	>Tradename	>Generic Name	>Dosage	>NDA	>Approval Date	>TE	>Type	>RLD	>RS	>Patent No.	>Patent Expiration	>Product	>Substance	>Delist Req.	>Patented / Exclusive Use	>Submissiondate

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	2114383	⤷ Start Trial	300797	Netherlands	⤷ Start Trial
European Patent Office	2114383	⤷ Start Trial	CA 2016 00007	Denmark	⤷ Start Trial
European Patent Office	2114383	⤷ Start Trial	CR 2016 00007	Denmark	⤷ Start Trial
European Patent Office	2114383	⤷ Start Trial	122016000023	Germany	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 10,245,228

Which drugs does patent 10,245,228 protect, and when does it expire?

Summary for Patent: 10,245,228