Details for Patent: 5,232,438

Summary for Patent: 5,232,438

Title:	Membrane for electrotransport transdermal drug delivery
Abstract:	A membrane capable of inhibiting agent release from a delivery system when no electrical current is flowing and yet provide minimal impedance to electrically-assisted agent delivery, useful both for incorporating into electrotransport agent delivery systems and for use in measuring agent release rates in in vitro testing.
Inventor(s):	Felix Theeuwes, J. Richard Gyory, Ronald P. Haak
Assignee:	Alza Corp
Application Number:	US07/898,618
Patent Claim Types: see list of patent claims	Use; Delivery; Device;

United States Drug Patent 5,232,438: Claims, Scope, Expiration, and Iontophoretic Fentanyl Patent Landscape

US Patent No. 5,232,438 covers electrically assisted transdermal delivery of fentanyl, sufentanil, related analogues, and pharmaceutically acceptable salts through a body surface. Its claims reach three subject-matter categories: electrode assemblies, complete iontophoretic delivery devices, and methods of inducing analgesia. The patent issued on August 3, 1993, and its 17-year term expired on August 3, 2010. It no longer creates a blocking patent right in the United States.[1]

The patent was an important early patent for the technology later commercialized as IONSYS, a fentanyl iontophoretic transdermal system. Its present commercial value is historical and freedom-to-operate related rather than exclusivity based. Current competitive risk would arise from later device, reservoir, control-system, manufacturing, or regulatory patents, not from US 5,232,438 itself.

What does US Patent 5,232,438 protect?

US 5,232,438 protects the combination of an electrically powered electrotransport system and an analgesic drug selected from a defined opioid genus. The principal drug group is:

• Fentanyl
• Sufentanil
• Analogues of fentanyl
• Analogues of sufentanil
• Pharmaceutically acceptable salts of those compounds

The claims do not cover fentanyl as a molecule in isolation. They require a delivery architecture capable of electrically transporting the drug through a body surface.

Claim group	Claims	Protected subject matter
Electrode assembly	1-7	Electrode, electrical connection, and drug reservoir containing an iontophoretically deliverable analgesic
Complete device	8-12	Donor electrode, counter electrode, power source, and ionized or ionizable analgesic source
Method using an electrode assembly	13-19	Placement, electrical connection, and electrotransport delivery sufficient to induce analgesia
Method using donor and counter electrodes	20-24	Human analgesia method using a spaced donor/counter electrode configuration

The patent therefore combines product claims and method claims. It is not limited to a particular patch shape, adhesive, battery chemistry, reservoir material, waveform, or commercial product name unless those limitations are imported from the specification during claim construction.

How broad are the independent claims?

Claims 1, 8, 13, and 20 are the principal independent claims.

Claim 1: electrode assembly

Claim 1 requires:

1. An electrode assembly adapted for placement on a body surface.
2. An electrode.
3. A means for connecting the electrode to an electrical power source.
4. A drug reservoir electrically connected to the electrode.
5. An analgesic drug in a form susceptible to iontophoretic delivery.
6. A drug within the fentanyl, sufentanil, analogue, or salt genus.

The claim is functionally broad. It does not require a particular reservoir composition or dosage. “Adapted for” language focuses on the structure’s intended capability, while “susceptible to iontophoretic delivery” requires the drug and assembly to be capable of electrically assisted transport.

The claim does not necessarily require a complete two-electrode system. A donor electrode assembly with a reservoir may satisfy claim 1 if the remaining elements are present. Claims 8 and 20 expressly add a counter electrode assembly.

Claim 8: complete iontophoretic device

Claim 8 is directed to a system containing:

• A donor electrode assembly
• A counter electrode assembly
• A power source electrically connected to both
• An ionized or ionizable analgesic source in the donor assembly

This claim is more structurally defined than claim 1. It requires both donor and counter electrodes and a power source. A product lacking a separate counter electrode could face a stronger non-infringement position under claim 8, although the analysis would depend on the actual device architecture and claim construction.

Claim 13: method using an electrode assembly

Claim 13 requires actual steps:

• Placing the electrode assembly on a body surface
• Electrically connecting the drug reservoir to a power source
• Placing the reservoir in drug-transmitting relation with the body surface
• Delivering the drug by electrotransport
• Delivering at a rate sufficient to induce analgesia

This is a use claim. Mere manufacture or sale of a device may not, by itself, satisfy the method steps. Use by a patient, clinician, or institutional customer would be central to infringement analysis.

Claim 20: human method with counter electrode

Claim 20 adds:

• A human patient
• A donor electrode assembly
• A spaced counter electrode assembly
• Electrical connection to both electrodes
• Iontophoretic delivery at a rate sufficient to induce analgesia

Claim 20 is narrower than claim 13 because it expressly requires a human patient and a spaced counter electrode. The claims do not specify a particular pain indication, surgical procedure, treatment duration, or fentanyl dose.

What formulations and drugs are covered?

The dependent claims identify water-soluble fentanyl and sufentanil salts, but the independent claims cover a broader category of ionized or ionizable drugs.

Drug or formulation	Claim treatment
Fentanyl base	Potentially covered if present in an ionizable form susceptible to electrotransport
Water-soluble fentanyl salt	Expressly covered by claims 2, 6, 14, and 18
Sufentanil base	Potentially covered if ionized or ionizable and electrotransportable
Water-soluble sufentanil salt	Expressly covered by claims 3, 7, 15, and 19
Fentanyl analogues	Covered by the independent genus claims if within the legally construed analogue scope
Sufentanil analogues	Covered on the same basis
Non-ionizable analgesics	Generally outside the express drug limitation unless they fall within the claimed ionizable genus
Passive fentanyl patch	Outside the claim scope if it does not use electrotransport
Oral, injectable, or nasal fentanyl	Outside the claim scope absent the claimed electrode and electrotransport elements

The “analogue” language creates the largest scope question. The claims do not provide a closed structural list of analogues. A court would likely evaluate the term using the specification, prosecution history, technical meaning, and written-description support available at the filing date. A later-developed opioid that is only functionally similar to fentanyl would not automatically fall within the claims.

What current legal status and expiration date apply?

US 5,232,438 issued August 3, 1993, to Alza Corporation. Because it was an early-1990s patent, its ordinary term was 17 years from issuance under the pre-URAA patent-term regime. The patent therefore expired on August 3, 2010, absent an unusual term adjustment or restoration.[1][2]

Event	Date or status
Patent	US 5,232,438
Title	Iontophoretic delivery of fentanyl
Assignee associated with the patent	Alza Corporation
Issue date	August 3, 1993
Ordinary patent term	17 years from issue
Expiration	August 3, 2010
Current enforceability	Expired
Current US blocking effect	None from this patent

The expiration eliminates ordinary infringement liability for activities occurring after the expiration date. It does not erase historical infringement claims that accrued while the patent was in force, subject to applicable limitation periods and litigation rules.

What is the Orange Book status of US 5,232,438?

The patent is associated with the fentanyl iontophoretic product IONSYS, but it is not a current enforceable Orange Book barrier because it expired in 2010. The FDA approved IONSYS under NDA 021338 as a fentanyl iontophoretic transdermal system. The product used a preprogrammed electrical system to deliver fentanyl through the skin for acute postoperative pain management.[3][4]

FDA regulatory history includes:

Regulatory event	Status
Product	IONSYS fentanyl iontophoretic transdermal system
Active ingredient	Fentanyl hydrochloride
Route	Iontophoretic transdermal delivery
NDA	021338
Initial US approval	2006
Later approval history	Product was reintroduced after manufacturing-related withdrawal issues
Current commercial status	No current patent exclusivity from US 5,232,438

Orange Book listings must be analyzed by product, NDA, patent-use code, and expiration date. Even when a patent appears in an historical Orange Book record, an expired patent cannot support a current Paragraph IV-based market exclusion.

When did US 5,232,438 lose exclusivity?

The patent lost exclusivity on August 3, 2010. The patent’s expiry predates the principal commercial period for IONSYS and does not provide current protection for fentanyl iontophoretic products.

Regulatory exclusivity is separate. Any five-year new chemical entity exclusivity, three-year new clinical investigation exclusivity, or pediatric exclusivity associated with an FDA application would have been governed by the NDA and approval history, not by the patent’s expiration date. IONSYS contained fentanyl, an already-known active ingredient, so the relevant FDA exclusivity analysis would not be equivalent to that for a new molecular entity.[3][5]

Were there Paragraph IV challenges to US 5,232,438?

There is no current Paragraph IV barrier associated with the patent because it expired more than a decade ago. A Paragraph IV certification is relevant when an applicant challenges an unexpired Orange Book patent listed for an approved drug. It does not preserve exclusivity after patent expiration.

The principal generic-entry obstacle for an IONSYS-type product has been practical rather than limited to US 5,232,438:

• Demonstrating bioequivalence or therapeutic equivalence for an electrically controlled delivery system.
• Matching delivery rate and total delivered dose.
• Establishing device reliability and software or control performance.
• Reproducing drug-reservoir and electrode characteristics.
• Meeting FDA combination-product requirements.
• Addressing opioid safety, misuse, dosing, and human-factors controls.

An ANDA may be unavailable or unsuitable if the reference product’s device and delivery technology require substantial clinical or device-performance data. A 505(b)(2) pathway or another NDA-based pathway may be more commercially realistic depending on the proposed product and reference-product status.[5]

How strong was the patent estate for IONSYS?

US 5,232,438 was conceptually broad but legally vulnerable on several dimensions.

Strength factor	Assessment
Core concept	Strong historical coverage of electrically delivered fentanyl and sufentanil
Drug scope	Broad genus, but analogue boundaries could be contested
Device scope	Broad in claim 1; more defined in claims 8 and 20
Formulation scope	Limited detail in the claims; water-soluble salts are expressly recited only in dependent claims
Dose protection	No express dose, concentration, or cumulative-dose limitation
Current term	None; expired
Design-around risk	Significant for non-electrotransport systems and materially different architectures
Commercial relevance	Historical; no current blocking value

The patent’s strongest feature was the combination of electrotransport and opioid analgesics. Its principal weakness was the absence of detailed limitations around a specific commercial implementation. A competing device could potentially avoid particular claims by changing the electrode arrangement, eliminating a separate counter electrode, using a different delivery mechanism, or selecting a drug outside the legally construed analogue genus.

Later patents could still have protected IONSYS-specific implementations. Those could include disposable electrode cartridges, dose-control electronics, activation systems, reservoir chemistry, tamper resistance, battery integration, and manufacturing methods. A complete freedom-to-operate opinion therefore cannot be based on US 5,232,438 alone.

What patent litigation and settlement issues affect this patent?

No current litigation or settlement can restore the expired patent’s exclusionary effect. Historical litigation would be relevant only to:

• Prior infringement occurring before August 3, 2010.
• Claim construction or validity findings that affect related continuation patents.
• License obligations that extend beyond the patent term through contract rather than patent law.
• Settlement restrictions tied to other unexpired patents or regulatory rights.

A settlement involving later IONSYS patents, device patents, or commercial rights would not automatically apply to US 5,232,438. Patent-by-patent and agreement-by-agreement review is required.

Which companies are challenging or competing with fentanyl iontophoretic delivery?

The competitive field separates into three groups:

Segment	Representative products or participants	Relationship to US 5,232,438
Iontophoretic fentanyl	IONSYS and successor commercial rights holders	Direct technology category
Passive transdermal fentanyl	Duragesic and generic fentanyl patches	Outside the electrotransport limitation
Non-transdermal fentanyl	Injectable, buccal, sublingual, and intranasal products	Generally outside the claim scope

The expiration of US 5,232,438 permits development of fentanyl iontophoretic systems without a license to that patent. Commercial entry still requires a viable product, FDA authorization, controlled-substance compliance, validated manufacturing, and a separate patent search covering later device and formulation claims.

What generic launch risks exist after patent expiration?

The patent-expiration risk is low. The product-development risk remains high.

A potential entrant would need to evaluate:

1. Device equivalence and electrical performance.
2. Delivery-rate reproducibility across skin types and application conditions.
3. Reservoir stability and fentanyl salt compatibility.
4. Human-factors risks, including accidental activation and repeated dosing.
5. Opioid labeling and abuse-deterrence considerations.
6. Combination-product manufacturing controls.
7. Later patents owned by Alza, Johnson & Johnson, The Medicines Company, or other developers.
8. Freedom to operate in the United States and foreign markets.

Manufacturing know-how can remain commercially important after patent expiration, but trade secrets cannot prevent independent development or lawful reverse engineering of publicly sold products in every circumstance. The key legal barrier is the later patent estate, not US 5,232,438.

How does US 5,232,438 compare with passive fentanyl patch patents?

US 5,232,438 differs from passive transdermal fentanyl patents in the required transport mechanism.

Issue	US 5,232,438	Passive fentanyl patch
Driving force	Electrical current	Diffusion
Core hardware	Donor electrode, often counter electrode, power source	Patch, adhesive, membrane, reservoir
Drug form	Ionized or ionizable fentanyl-family compound	Form suitable for passive skin permeation
Main claim focus	Electrotransport delivery	Patch construction and sustained diffusion
Dose control	Electrical delivery profile	Patch area, concentration, membrane, and diffusion
Typical design-around	Passive or non-iontophoretic delivery	Electrical delivery would create a different patent analysis

A passive fentanyl patch does not ordinarily infringe US 5,232,438 because the patent requires electrical electrotransport elements. Conversely, an iontophoretic product may avoid passive-patch claims but still face later patents directed to electronics, reservoirs, adhesives, or dosing controls.

Key Takeaways

• US 5,232,438 covers iontophoretic delivery of fentanyl, sufentanil, related analogues, and salts.
• The claims cover electrode assemblies, complete donor-counter electrode devices, and analgesia-inducing methods.
• Water-soluble fentanyl and sufentanil salts are expressly covered by dependent claims.
• The patent issued August 3, 1993, and expired August 3, 2010.
• It creates no current US patent exclusivity or Paragraph IV barrier.
• IONSYS is the principal commercial product associated with the technology.
• Passive fentanyl patches and non-electrical fentanyl products generally fall outside the claims.
• Current commercial risk depends on later patents, FDA pathway selection, device performance, manufacturing controls, and opioid-product regulation.
• A current freedom-to-operate analysis must review continuation patents and later device, formulation, software, reservoir, and manufacturing patents.

FAQs

Does US 5,232,438 cover fentanyl itself?

No. It covers fentanyl when used in the claimed iontophoretic electrode assembly, device, or method. The patent does not claim fentanyl as a standalone chemical compound.

Can a company commercialize an iontophoretic fentanyl device without licensing US 5,232,438?

Yes, the patent expired in 2010. The company must still assess later US patents and obtain the required FDA authorization.

Does a fentanyl hydrochloride reservoir fall within the patent claims?

It may. Fentanyl hydrochloride is a water-soluble fentanyl salt, and the dependent claims expressly identify water-soluble fentanyl salts. The device must also satisfy the electrode, reservoir, power, and electrotransport limitations.

Are sufentanil products covered to the same extent as fentanyl products?

The claims expressly include sufentanil and pharmaceutically acceptable sufentanil salts. The same electrotransport and device limitations apply.

Is a modern wearable fentanyl patch automatically covered by this patent?

No. A wearable product must satisfy the patent’s specific electrotransport and drug limitations. A passive diffusion patch generally lacks the required electrical delivery elements.

References

1. United States Patent and Trademark Office. (1993). U.S. Patent No. 5,232,438: Iontophoretic delivery of fentanyl. https://patents.google.com/patent/US5232438A/en

2. United States Code. (2024). 35 U.S.C. § 154: Contents and term of patent; provisional rights. https://uscode.house.gov/view.xhtml?req=granuleid:USC-prelim-title35-section154

3. U.S. Food and Drug Administration. (2015). IONSYS (fentanyl iontophoretic transdermal system) prescribing information. https://www.accessdata.fda.gov/drugsatfda_docs/label/

4. U.S. Food and Drug Administration. (2024). Orange Book: Approved drug products with therapeutic equivalence evaluations. https://www.accessdata.fda.gov/scripts/cder/ob/

5. U.S. Food and Drug Administration. (2024). Abbreviated new drug application and 505(b)(2) regulatory pathways. https://www.fda.gov/drugs/development-resources/frequently-asked-questions-about-generic-drugs

Drugs Protected by US Patent 5,232,438

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate

International Family Members for US Patent 5,232,438

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	234130
Austria	235284
Australia	2987692