United States Patent 3,998,834: Scope, Claims, Expiration, and Sufentanil Patent Landscape

US 3,998,834 is a foundational 4-anilidopiperidine patent assigned to Janssen Pharmaceutica. Its claims cover a broad genus of substituted 4-anilidopiperidines, including compounds corresponding to sufentanil and related fentanyl analogs. The patent issued on December 21, 1976, and its ordinary pre-1995 patent term expired in December 1993. It has no current blocking force against generic manufacture, formulation, or commercialization. Its commercial significance is historical: later patents, regulatory exclusivities, and formulation patents, rather than US 3,998,834 itself, govern modern sufentanil products.

What compounds does US 3,998,834 cover?

The patent covers substituted 4-anilidopiperidines with variation at several positions:

Structural region	Claim scope
Piperidine ring	4-anilino substituted piperidine core
Anilino ring	Hydrogen, halogen, lower alkyl, lower alkoxy, or trifluoromethyl substitution
Piperidine nitrogen	Alkyl, cycloalkylmethyl, arylalkyl, arylhydroxyalkyl, arylcarbonylalkyl, arylaminethyl, alkenyl, indanyl, and related groups
4-position substituent	Carboxylate, alkanoyl, or oxymethyl derivative
Stereochemistry	Optical isomers and, for specified compounds, cis stereoisomers
Salt forms	Pharmaceutically acceptable acid-addition salts for many claims

The claim architecture is designed to protect both the active 4-anilidopiperidine nucleus and substituent combinations that modify potency, lipophilicity, duration, metabolism, and formulation properties.

The chemical drawings referenced in the supplied text are not reproduced. The scope analysis therefore relies on the written Markush definitions and the expressly named compounds in claims 2 through 17.

What is the scope of independent claim 1?

Claim 1 is the principal broad genus claim. It covers a piperidine derivative having the patent’s core formula, together with pharmaceutically acceptable acid-addition salts and stereochemical optical isomers.

Its breadth comes from four variables:

The anilino substituent Z.
The piperidine nitrogen substituent L.
The ring variable X, defined as hydrogen or methyl.
The 4-position group R1.

R1 may be:

A carboxylate radical, with lower alkyl, lower alkenyl, or benzyl substitution.
An alkanoyl radical, with lower alkyl substitution.
An oxymethyl radical, with hydrogen, lower alkyl, benzyl, or lower alkylcarbonyl substitution.

The two provisos materially narrow the broad Markush definition. They exclude particular combinations of the R1 and L substituents. These restrictions reduce overlap between compound classes and distinguish the claimed compounds from structures that may have been disclosed elsewhere in the patent or prior art.

Claim 1 is therefore a composition-of-matter claim, not a method-of-use claim. It does not require a particular dosage form, therapeutic indication, manufacturing process, purity level, or pharmaceutical excipient.

Which specifically named compounds are claimed?

Claims 2 through 11 identify individual compounds or closely defined compound classes. The most commercially significant is claim 2:

N-[4-(methoxymethyl)-1-[2-(2-thienyl)ethyl]-4-piperidinyl]-N-phenylpropanamide.

This compound is sufentanil. Claim 2 covers sufentanil and its pharmaceutically acceptable acid-addition salts.

The other named compounds include phenethyl, thienylethyl, methyl-substituted, acetyl, cyclopropanecarbonyl, and methoxymethyl analogs. Their claim significance is summarized below.

Claim	Named subject matter	Patent function
2	Sufentanil and acid-addition salts	Direct species claim for sufentanil
3	Methyl 4-[(1-oxopropyl)phenylamino]-1-(2-phenylethyl)-4-piperidinecarboxylate	Specific ester analog
4	Thienylethyl ester analog	Specific sulfur-containing analog
5	1-Methyl-2-phenylethyl ester analog	N-substituent stereochemical and structural variant
6	3-Methyl piperidine ester analog	Ring-methyl analog
7	Cis form of claim 6	Stereochemically restricted species
8	Cyclopropanecarbonyl analog	Acyl variation
9	4-Acetyl phenethyl analog	Ketone-substituted analog
10	4-Acetyl cyclopropanecarboxamide analog	Combined acyl and N-acyl variation
11	4-Methoxymethyl phenethyl analog	Sufentanil-related phenethyl compound

Claims 13 through 17 recite additional compounds, including unsubstituted 4-piperidinecarboxylate derivatives and cis-methyl compounds. They are narrower species claims and would be easier to analyze for literal infringement than claim 1.

Does US 3,998,834 cover sufentanil?

Yes. Claim 2 expressly covers sufentanil as identified by its chemical name. The patent is one of the key early composition-of-matter patents in the sufentanil lineage.

Sufentanil is a synthetic opioid used primarily for anesthesia and perioperative analgesia. The FDA approved Sufenta injection in the United States before the later development of sublingual sufentanil products. The FDA-approved label identifies sufentanil citrate as the active drug substance in the injectable product (U.S. Food and Drug Administration, 2018a).

The patent’s claim to sufentanil includes:

The free-base chemical entity, to the extent covered by the claim language.
Pharmaceutically acceptable acid-addition salts.
The stereochemical forms included within the claim.

The most commercially relevant salt is sufentanil citrate.

When did US 3,998,834 lose exclusivity?

The patent issued on December 21, 1976. For a United States patent issued before the 1995 patent-term transition, the ordinary term was 17 years from grant under the then-applicable version of 35 U.S.C. § 154.

Event	Date
Patent issued	December 21, 1976
Ordinary 17-year term	December 21, 1993
Current enforceability	Expired
Current composition-of-matter exclusivity	None

No patent-term extension under the modern Hatch-Waxman framework could extend the patent into the present because the patent expired before the relevant later regulatory products and before the modern patent-term-extension framework could provide commercial protection for those products.

The patent’s expiration means that a party does not need a license from Janssen to practice the claimed sufentanil compounds in the United States. A separate patent could still cover a later formulation, delivery system, manufacturing process, or method of use.

What is the Orange Book status of US 3,998,834?

US 3,998,834 is not a current Orange Book barrier. The Orange Book lists patents submitted by NDA holders for approved drug products, but an expired 1976 composition patent does not create an operative patent certification barrier for a current ANDA applicant.

The patent is not expected to support:

A current Paragraph IV challenge.
A 30-month stay under 21 U.S.C. § 355(j)(5)(B)(iii).
A current patent-based delay to generic approval.
A current patent-term extension.
A current pediatric exclusivity period.

Modern sufentanil products must be evaluated separately. The relevant Orange Book analysis depends on the specific reference-listed drug, dosage form, route of administration, NDA holder, and currently listed patents. Injectable sufentanil and sublingual sufentanil products should not be treated as having the same patent estate.

What later patents protect sufentanil products?

The main post-1993 protection opportunities have concerned delivery and formulation rather than the sufentanil molecule itself.

Injectable sufentanil

Older injectable sufentanil products generally face limited composition-of-matter protection because the foundational compound patent expired decades ago. Potential later protection may concern:

Manufacturing controls.
Sterile production.
Container-closure systems.
Concentration or dilution formats.
Stability and storage.
Specific clinical-use methods.

These rights are narrower than a compound patent and usually do not prevent all generic sufentanil injections.

Sublingual sufentanil

DSUVIA is a sublingual sufentanil tablet approved by the FDA in 2018. Its product profile differs materially from injectable sufentanil because the commercial value rests on the sublingual delivery system, tablet design, dosing control, and use setting.

The relevant patent risks for a DSUVIA-type product may include:

Sublingual tablet composition.
Rapid dissolution and transmucosal absorption.
Sufentanil particle characteristics.
Dose uniformity.
Mucoadhesive or disintegration technology.
Applicator and administration systems.
Restricted-use distribution controls.

Those rights do not revive US 3,998,834 and do not extend the expired compound patent.

Are there biosimilar risks?

No. Sufentanil is a small-molecule active pharmaceutical ingredient, not a biologic. The relevant regulatory pathways are:

ANDA approval for a therapeutically equivalent generic drug.
NDA or 505(b)(2) approval for a product with a changed formulation, route, dosage form, or clinical profile.

A sufentanil product is not subject to the biosimilar provisions of the Public Health Service Act. The competitive analysis should focus on generic entry, 505(b)(2) products, formulation patents, and regulatory exclusivities rather than biosimilar substitution.

Are there Paragraph IV challenges involving this patent?

A Paragraph IV certification against US 3,998,834 would have no current commercial utility because the patent expired in 1993. A generic applicant can proceed without certifying that the expired patent is invalid or will not be infringed.

Historical ANDA activity involving sufentanil may have included patent certifications against later-listed patents, but those proceedings should not be attributed to US 3,998,834 without a case-specific record. The foundational patent itself is no longer capable of supporting a Paragraph IV stay.

What litigation and settlement agreements affect the patent?

US 3,998,834 is too old to present a current enforcement risk. No active litigation based solely on this patent should be expected.

Any relevant modern litigation would more likely involve:

Later formulation patents for sublingual sufentanil.
Patent listings for specific NDA products.
Trade-secret claims involving manufacturing.
Regulatory exclusivity disputes.
Contract or licensing rights involving commercial products.

The expired patent should not be used as evidence of a current settlement restriction or continuing Janssen exclusivity.

How strong is the patent estate?

Historical strength

The patent had strong historical value because it combined:

A broad genus claim.
Species claims to commercially relevant analogs.
Salt protection.
Stereochemical coverage.
Multiple substituent classes.
Claims directed to both anesthetic opioid candidates and related intermediates or analogs.

Claim 2 was particularly valuable because it directly identified sufentanil rather than relying only on the broader Markush genus.

Current strength

Its current legal strength is zero as an enforceable patent because the term expired. Its residual value is limited to:

Prior-art status.
Historical ownership analysis.
Inventorship and priority research.
Freedom-to-operate baseline analysis.
Interpretation of later patent families.
Identification of the original chemical disclosure.

The patent does not block generic sufentanil API manufacture or ordinary finished-dose development today.

How does US 3,998,834 compare with later sufentanil protection?

Issue	US 3,998,834	Later sufentanil patents
Protection type	Compound and species claims	Formulation, delivery, process, or use claims
Main product	Sufentanil and analogs	Injectable or sublingual products
Expiration	1993	Product-specific
Generic impact	No current barrier	May affect specific dosage forms
Biosimilar relevance	None	None
Orange Book relevance	Historical only	Potentially current if listed
Licensing significance	Foundational historical right	Product-specific commercial rights
Workaround potential	Not relevant because expired	Depends on claim construction and formulation design

What generic launch scenarios exist?

For a conventional sufentanil injection, the main entry scenario is an ANDA relying on the reference product’s safety and efficacy findings, subject to pharmaceutical equivalence, bioequivalence, manufacturing, and quality requirements.

For a sublingual sufentanil product, entry is more complex. A competitor may need to select among:

A standard ANDA strategy if the product can meet therapeutic-equivalence requirements.
A 505(b)(2) strategy if the dosage form, delivery technology, or clinical use differs materially.
A non-infringing formulation designed around later delivery-system claims.
A different administration route, such as injectable rather than sublingual delivery.

The expired compound patent does not prevent any of these strategies. The principal risk is later patent coverage tied to the specific product architecture.

Key Takeaways

US 3,998,834 is a Janssen 4-anilidopiperidine patent issued December 21, 1976.
Claim 2 expressly covers sufentanil and its pharmaceutically acceptable acid-addition salts.
The patent’s ordinary term expired in December 1993.
The patent has no current Orange Book, Paragraph IV, or generic-entry blocking effect.
It is a small-molecule patent and creates no biosimilar issue.
Modern sufentanil risks arise from later formulation, delivery, manufacturing, and method-of-use patents.
Injectable and sublingual sufentanil products require separate patent and Orange Book analyses.
Claims 13 through 17 are narrow species claims, while claim 1 is the principal broad Markush claim.
The patent remains important as a historical foundation for the sufentanil chemical family, but not as a live enforceable right.

FAQs

Is US 3,998,834 the original sufentanil patent?

It is a foundational early patent that expressly claims sufentanil. It is not a current enforceable patent because its term expired in 1993.

Can a company manufacture sufentanil in the United States without a license to Janssen?

Yes, US 3,998,834 no longer requires a license. Separate later patents, regulatory requirements, contractual rights, or manufacturing restrictions may still apply to a particular product.

Does the patent cover sufentanil citrate?

Claim 2 covers sufentanil and pharmaceutically acceptable acid-addition salts. Sufentanil citrate falls within that salt category, subject to the claim’s chemical limitations.

Does US 3,998,834 cover DSUVIA?

It covers the sufentanil active ingredient historically, but it does not provide current enforceable protection for DSUVIA. DSUVIA’s current patent position depends on later patents covering its sublingual formulation, delivery system, and related product characteristics.

Is a generic sufentanil applicant required to file Paragraph IV against this patent?

No. An expired patent does not create a current Paragraph IV barrier or support a 30-month stay.

References

Janssen Pharmaceutica N.V. (1976). 4-Anilidopiperidine derivatives, U.S. Patent No. 3,998,834. United States Patent and Trademark Office.
U.S. Food and Drug Administration. (2018a). Sufenta (sufentanil citrate) injection prescribing information. FDA.
U.S. Food and Drug Administration. (2018b). DSUVIA (sufentanil sublingual tablet) prescribing information. FDA.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations. FDA.
United States Code. (1993). 35 U.S.C. § 154: Contents and term of patent; provisional rights. Legal Information Institute.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	359493	⤷ Start Trial
Austria	A184676	⤷ Start Trial
Australia	1200676	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 3,998,834

Summary for Patent: 3,998,834