United States Patent 6,216,033: Claim Scope, Expiration, Orange Book Relevance, and Fentanyl Electrotransport Patent Landscape

US 6,216,033 covers a patient-worn, patient-controlled electrotransport device for delivering defined doses of fentanyl or sufentanil through the skin. Its strongest protection is directed to the combined product architecture and operating regimen: a drug-containing hydrogel donor reservoir, counter reservoir, electrical power source, current-control circuit, patient activation switch, timed delivery, and repeated self-administration over 24 hours.

The patent is no longer an active blocking right in the United States. Because it issued in 2001 from an application filed well before issuance, its ordinary 20-year patent term would have expired no later than 2021, subject to the specific priority and patent-term-adjustment record. The claims remain commercially important as prior-art and freedom-to-operate references, but they should not independently prevent U.S. commercialization in 2026.

What does US 6,216,033 protect?

The patent protects a device, not fentanyl or sufentanil as chemical compounds. Every independent claim requires a specific combination of hardware, formulation, delivery mechanism, dose, timing, and patient-use controls.

Claim group	Drug	Core dose range	Delivery period	Repeated-use limitation
Claim 1	Fentanyl	About 20-60 micrograms	Up to about 20 minutes	About 10-100 additional doses in 24 hours
Claims 2-5	Fentanyl	35-45 micrograms, or 40 micrograms	5-15 minutes, or 10 minutes	Depends from claim 1
Claims 6-9	Fentanyl	Same as claim 1	Same as claim 1	Salt, concentration, and PVA limitations
Claim 10	Sufentanil	About 2.3-7.0 micrograms	Up to about 20 minutes	About 10-100 additional doses in 24 hours
Claims 11-14	Sufentanil	4-5.5 micrograms, or 4.7 micrograms	5-15 minutes, or 10 minutes	Depends from claim 10
Claims 15-18	Sufentanil	Same as claim 10	Same as claim 10	Salt, concentration, and PVA limitations

The claims are drafted as combination claims. A competing product would generally need to satisfy all limitations of an asserted claim, either literally or under the doctrine of equivalents, before infringement would be established.

How are the independent claims structured?

Claim 1: fentanyl electrotransport device

Claim 1 requires:

A patient-worn device.
Transdermal fentanyl delivery.
Electrotransport as the delivery mechanism.
A donor reservoir containing fentanyl in a form intended to be delivered solely by electrotransport.
A counter reservoir.
An electrical power source connected to both reservoirs.
A current-control circuit.
A patient-controlled activation switch.
A dose of about 20-60 micrograms.
Delivery over a predetermined period of up to about 20 minutes.
Automatic termination at the end of that period.
The ability to administer about 10-100 additional doses during 24 hours.

The claim does not cover every transdermal fentanyl product. Conventional fentanyl patches that rely on passive diffusion do not meet the electrotransport limitation. Injectable fentanyl, buccal fentanyl, nasal fentanyl and inhaled fentanyl products also fall outside the claim because they lack the claimed device architecture.

Claim 10: sufentanil electrotransport device

Claim 10 has substantially the same architecture but substitutes sufentanil and narrows the dose range to about 2.3-7.0 micrograms.

The sufentanil claims are technically significant because they protect a lower-dose electrotransport regimen for a more potent opioid. The claims do not require that sufentanil be commercially marketed, nor do they require a particular clinical indication beyond patient self-administration for pain.

What formulations are protected by US 6,216,033?

Fentanyl and sufentanil salts

Claims 6 and 15 require a fentanyl or sufentanil salt. Claims 8 and 17 specify the hydrochloride salts:

Fentanyl hydrochloride.
Sufentanil hydrochloride.

Claims 7 and 16 specify a salt concentration of about 1.9% to 2.0% by weight of the hydrogel formulation.

The concentration limitation is material. A formulation containing fentanyl hydrochloride at a materially different concentration may fall outside claims 7 and 8, although it could still fall within claim 1 if the device and dosing limitations are met.

Polyvinyl alcohol

Claims 9 and 18 require a hydrogel formulation comprising polyvinyl alcohol, commonly abbreviated PVA.

Because the term “comprising” is open-ended, a formulation may contain PVA and additional polymers, buffers, excipients or conductivity agents without automatically leaving the claim scope. The claims do not require PVA to be the only polymer or the majority component.

“Solely by electrotransport”

The phrase “solely by electrotransport” is a central limitation. It distinguishes the claimed device from a hybrid system in which fentanyl is delivered partly by passive diffusion, osmotic flow, mechanical pumping or another transport mechanism.

A product using an iontophoretic current to enhance a drug reservoir but also relying materially on passive diffusion would present a claim-construction issue. The patent owner would likely argue that the limitation concerns the intended delivery mode, while an accused party would argue that mixed transport defeats the “solely” requirement.

How do the dependent claims narrow the patent?

The dependent claims create commercially recognizable embodiments:

Claims 2 and 11: intermediate dose ranges and 5-15 minute delivery.
Claims 3 and 12: approximately 40 micrograms of fentanyl or 4.7 micrograms of sufentanil.
Claims 4 and 13: lower-dose treatment for less severe pain.
Claims 5 and 14: approximately 10-minute delivery.
Claims 6 and 15: drug salt.
Claims 7 and 16: approximately 1.9%-2.0% salt concentration.
Claims 8 and 17: hydrochloride salt.
Claims 9 and 18: PVA-containing hydrogel.

Claims 3 and 5 are particularly relevant to the commercial IONSYS configuration because a 40-microgram fentanyl dose delivered over approximately 10 minutes falls within both limitations when the other elements are present.

How does US 6,216,033 compare with IONSYS?

IONSYS was a fentanyl hydrochloride iontophoretic transdermal system developed initially by ALZA and later commercialized by other entities. The FDA-approved product delivered a 40-microgram dose over 10 minutes after patient activation, subject to device-imposed limits on repeated dosing.[2]

Attribute	Claim 3 / Claim 5 embodiment	IONSYS commercial configuration
Active ingredient	Fentanyl	Fentanyl hydrochloride
Dose per activation	About 40 micrograms	40 micrograms
Delivery period	About 10 minutes	Approximately 10 minutes
Administration	Patient-controlled	Patient-controlled
Route	Transdermal	Transdermal
Mechanism	Electrotransport	Iontophoretic electrotransport
Reservoir	Hydrogel donor reservoir required by claims	Drug reservoir and iontophoretic system
Use setting	Patient-worn analgesic device	Acute postoperative pain

The product profile closely matches the narrower fentanyl claims. That alignment explains the patent’s commercial relevance during the period in which IONSYS was approved and marketed.

The patent did not protect every feature of the IONSYS product. Separate patents and regulatory exclusivities could have covered device construction, electrode materials, reservoir design, packaging, software controls, manufacturing, safety interlocks or other product features.

When did US 6,216,033 lose exclusivity?

US 6,216,033 is expired in the United States as of 2026.

The ordinary U.S. patent term for a utility patent is generally 20 years from the earliest effective nonprovisional filing date, subject to patent-term adjustment, patent-term extension and terminal disclaimers.[3] The patent issued on April 17, 2001. Its term therefore was not calculated as 20 years from the issue date.

No ordinary patent term can extend this patent into 2026 solely because the patent issued in 2001. Any FDA regulatory exclusivity associated with an approved fentanyl device would also have been separate from patent term and would not revive an expired patent.

Exclusivity timeline

Event	Timing
Patent application and priority chain	Before April 17, 2001
US 6,216,033 issued	April 17, 2001
IONSYS FDA approval	2006
Initial commercial and regulatory activity	2006 onward
U.S. patent term	Expired before 2026
Current blocking status	No enforceable patent exclusion based solely on US 6,216,033

The exact statutory expiration date should be taken from the USPTO patent-term record and the complete priority chain. The practical conclusion is unchanged: the patent is expired.

What is the Orange Book status of US 6,216,033?

The Orange Book evaluates patents and exclusivities associated with approved drug products. It does not convert an expired patent into an enforceable right.

IONSYS was listed in FDA drug-product materials as a fentanyl iontophoretic system. Historical Orange Book information may identify patents associated with the product, but any listing for US 6,216,033 would now have historical significance only because the patent has expired.[4]

The patent is not a biosimilar patent. Fentanyl and sufentanil are small-molecule active ingredients, so the relevant abbreviated pathway is an ANDA or, depending on the product, a 505(b)(2) application. Biosimilar procedures under section 351(k) do not apply.

Which companies challenged or could challenge the patent?

A Paragraph IV challenge would have been relevant while the patent was listed and unexpired. An ANDA applicant could have alleged that the patent was:

Invalid.
Unenforceable.
Not infringed.
Not properly listed for the proposed product.

Because US 6,216,033 is expired, a new Paragraph IV challenge against this patent would have little commercial purpose. An applicant may still address the patent in a regulatory certification or patent statement, but the patent would not support a 30-month stay against an ANDA based on a newly filed infringement action.

The greater current risk lies in other rights, including:

Device-control patents.
Electrode and reservoir patents.
Manufacturing-process patents.
Product-specific formulation patents.
Know-how and regulatory documentation.
Trademarks and proprietary device software.

The supplied claim set does not identify a current litigation defendant, settlement agreement, license, or covenant not to sue. Those issues cannot be inferred from the patent claims.

What patent litigation affects US 6,216,033?

The claim text alone does not establish litigation history. Patent litigation must be assessed from PACER, district-court dockets, Federal Circuit decisions, USPTO prosecution files and FDA patent-listing records.

From a legal-risk perspective, an expired patent can still affect disputes in three ways:

It can operate as prior art against later patent applications.
Its prosecution history can inform claim construction of related patents.
Its technical disclosures can support invalidity or obviousness arguments against continuation, divisional or related patents.

The expired patent cannot ordinarily support a new U.S. infringement damages claim for conduct occurring after expiration.

How strong was the patent estate?

Strengths

The patent had strong product-specific coverage during its enforceable term because the principal commercial embodiment aligned closely with the claims:

40-microgram fentanyl dosing.
Approximately 10-minute delivery.
Patient-controlled activation.
Transdermal iontophoresis.
Hydrogel reservoir.
Repeated dosing over 24 hours.

The dependent claims also provided fallback positions for salt, concentration and PVA limitations.

Weaknesses

The claims had several potential vulnerability points:

“About” creates boundary questions around dose, concentration and timing.
“Solely by electrotransport” may be difficult to apply to systems with mixed transport.
The claims require a particular control regimen, limiting coverage of differently programmed devices.
The 10-100 additional dose range may exclude devices with materially lower or higher permitted dosing.
The claims are device combinations and do not independently cover the fentanyl molecule, fentanyl hydrochloride or passive transdermal delivery.
Prior art in iontophoresis, patient-controlled analgesia and opioid delivery could have supported novelty or obviousness challenges.

The patent’s commercial strength was therefore high for a matching IONSYS-type product but lower for alternative delivery systems.

What generic launch scenarios exist?

Scenario 1: Passive fentanyl patch

A conventional fentanyl patch generally avoids the core electrotransport requirement. It would require separate analysis under patch formulation and method-of-use patents, but US 6,216,033 would not be the principal barrier.

Scenario 2: Iontophoretic fentanyl device

A new device delivering approximately 40 micrograms over 10 minutes could have matched claims 1, 3 and 5. The patent’s expiration removes that obstacle, but active patents covering device engineering, software, packaging or manufacturing could remain relevant.

Scenario 3: Different dose or delivery period

A device delivering a materially different dose or over a substantially different period may avoid the narrower dependent claims. It could still fall within claim 1 or claim 10 if it remains within the broad ranges and meets every structural limitation.

Scenario 4: Passive-plus-electrical delivery

A system that combines electrotransport with substantial passive diffusion may create a defense under the “solely by electrotransport” limitation. The outcome would depend on claim construction and technical evidence.

Scenario 5: Sufentanil product

Claims 10-18 cover sufentanil embodiments, including sufentanil hydrochloride and PVA hydrogel formulations. No commercial U.S. product matching the claimed sufentanil device configuration is established by the claim text. A sufentanil product would require separate FDA, controlled-substance, clinical, formulation and manufacturing analysis.

What manufacturing and IP barriers remain?

The patent does not eliminate technical barriers to a new electrotransport opioid system. Key barriers include:

Uniform drug loading in a hydrogel reservoir.
Stable fentanyl salt concentration.
Electrode compatibility and corrosion control.
Accurate current delivery.
Dose reproducibility across skin types.
Adhesion during patient movement.
Activation-lockout and overdose-prevention controls.
Battery life and failure-mode management.
Manufacturing controls for a Schedule II opioid.
Human-factors validation.
Abuse-deterrence and diversion controls.
Combination-product quality systems.

These issues may be protected by later patents or retained as trade secrets even after US 6,216,033 expired.

What geographic coverage does the patent have?

US 6,216,033 provides rights only in the United States. It does not establish protection in Europe, Canada, Japan, China or other jurisdictions.

International protection would depend on separate national patents or regional grants derived from the same priority family. Patent term and legal status must be evaluated independently in each jurisdiction. Expiration of the U.S. patent does not determine the status of foreign family members.

Key Takeaways

US 6,216,033 covers patient-worn electrotransport devices for self-administered fentanyl or sufentanil.
Claims 1 and 10 are the two independent claim families.
The principal fentanyl embodiment is approximately 40 micrograms delivered over approximately 10 minutes.
The claims require a hydrogel donor reservoir, counter reservoir, electrical power, current control and patient activation.
“Solely by electrotransport” is a major claim limitation.
Claims 6-9 and 15-18 add salt, concentration, hydrochloride and PVA limitations.
The claims closely correspond to the core operating profile of IONSYS.
The U.S. patent expired before 2026 and is no longer an independent blocking patent.
Fentanyl and sufentanil are small molecules; biosimilar analysis does not apply.
Current commercial risk would come from later device, formulation, manufacturing, software or regulatory patents rather than this expired patent.
The patent covers the United States only and does not establish foreign rights.

FAQs

Does US 6,216,033 cover ordinary fentanyl patches?

No. The claims require delivery solely by electrotransport. Passive-diffusion fentanyl patches generally lack that limitation.

Does the patent cover a fentanyl injection pump?

No. An injection pump does not ordinarily have a transdermal electrotransport donor reservoir and counter reservoir as required by the claims.

Can a company launch an iontophoretic fentanyl product after expiration?

US 6,216,033 alone would not block launch after expiration. The company would still need to clear later patents, regulatory requirements, controlled-substance obligations and product-specific IP.

Does the patent protect fentanyl hydrochloride as a compound?

No. Claims 6-8 address fentanyl salt formulations within the claimed electrotransport device. They do not claim fentanyl hydrochloride as a chemical substance independent of the device.

Are sufentanil electrotransport claims commercially relevant today?

They remain relevant as technical and prior-art disclosures, but the patent itself does not provide an enforceable U.S. exclusion after expiration. A current sufentanil product would require a separate review of active patents and FDA requirements.

References

United States Patent and Trademark Office. (2001). U.S. Patent No. 6,216,033, Electrotransport delivery of fentanyl and sufentanil.
U.S. Food and Drug Administration. (2015). IONSYS fentanyl iontophoretic transdermal system prescribing information.
35 U.S.C. §§ 154, 156.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book.

PCT Information
PCT Filed	May 22, 1996	PCT Application Number:	PCT/US96/07380
PCT Publication Date:	December 12, 1996	PCT Publication Number:	WO96/39222

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	0836511	⤷ Start Trial	91265	Luxembourg	⤷ Start Trial
European Patent Office	0836511	⤷ Start Trial	CA 2006 00019	Denmark	⤷ Start Trial
European Patent Office	0836511	⤷ Start Trial	SPC/GB06/022	United Kingdom	⤷ Start Trial
European Patent Office	0836511	⤷ Start Trial	122006000022	Germany	⤷ Start Trial
Austria	263597	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Summary for Patent: 6,216,033