US Drug Patent RE38115: Claim Scope, Expiration, Litigation Risk, and Related Dextromethorphan Patent Landscape

US Reissue Patent RE38115 covered combinations of dextromethorphan with inhibitors of debrisoquin hydroxylase, now generally understood as CYP2D6 inhibitors. Its claims targeted four uses: chronic or intractable pain, tinnitus, sexual dysfunction, and an oral unit-dose formulation for pain.

The patent was a method-and-composition patent rather than a claim to dextromethorphan itself. Its practical value depended on proving that a product or treatment used dextromethorphan with a listed inhibitor, achieved the claimed therapeutic effect, and, for quinidine claims, stayed within the stated dosage ceiling. The patent term has expired, so RE38115 does not presently create an enforceable US exclusivity barrier.

What does US Patent RE38115 claim?

RE38115 contains 22 claims, with five independent claims:

Independent claim	Claim type	Subject matter
Claim 1	Method	Dextromethorphan plus a debrisoquin hydroxylase inhibitor for chronic or intractable pain
Claim 5	Method	Dextromethorphan plus an inhibitor at combined dosages that reduce pain without unacceptable side effects
Claim 9	Method	Dextromethorphan plus an inhibitor for tinnitus
Claim 13	Method	Dextromethorphan plus an inhibitor for sexual dysfunction
Claim 18	Composition	Oral unit dosage formulation containing dextromethorphan and an inhibitor for pain

The patent uses the older term “debrisoquin hydroxylase inhibitor.” In modern pharmacology, the relevant enzyme is CYP2D6, which metabolizes dextromethorphan into dextrorphan. Inhibiting CYP2D6 increases systemic exposure to dextromethorphan and can extend its half-life.

Which compounds fall within the claimed inhibitor groups?

The claims divide the inhibitors into two Markush groups:

Group	Listed compounds
Group 1	Quinidine, quinine, and pharmaceutically acceptable salts
Group 2	Disulfiram, fluoxetine, propranolol, nortriptyline, and pharmaceutically acceptable salts

Claims 2, 6, 10, 15 and 20 cover the first group. Claims 4, 8, 12, 17 and 22 cover the second group.

The claims do not expressly require a particular CYP2D6 inhibition constant, plasma concentration, dextromethorphan-to-quinidine ratio, dosage form, or administration schedule, except where a dependent claim introduces a dosage limitation.

How broad are the method claims in RE38115?

The broadest claims are claims 1, 5, 9 and 13. Each requires a treatment involving:

A patient with the specified condition.
Administration of dextromethorphan or a pharmaceutically acceptable salt.
Administration of a debrisoquin hydroxylase inhibitor.
A therapeutic result or therapeutic purpose.

The claims are narrower than a claim to any dextromethorphan/CYP2D6-inhibitor combination because the treatment indication is essential.

Claim 1: chronic or intractable pain

Claim 1 requires administration of a therapeutically effective dose of dextromethorphan with a therapeutically effective dose of an inhibitor to increase dextromethorphan’s effectiveness in treating chronic or intractable pain.

The claim has several potentially important limitations:

The patient must suffer from chronic or intractable pain.
Both agents must be administered.
The inhibitor must qualify as a debrisoquin hydroxylase inhibitor.
The combination must increase dextromethorphan effectiveness.
The dosages must be therapeutically effective.

A product containing dextromethorphan alone would not fall within claim 1. A product containing dextromethorphan and an unrelated metabolic inhibitor would also fall outside the literal claim unless the inhibitor could properly be characterized as a debrisoquin hydroxylase inhibitor.

Claim 5: pain treatment without unacceptable side effects

Claim 5 focuses on the combined dosages and requires that they render dextromethorphan therapeutically effective in substantially reducing chronic or intractable pain without causing unacceptable side effects.

This claim may be harder to enforce than a simple ingredient-and-indication claim because it incorporates functional and outcome-oriented limitations. A litigation plaintiff would likely need evidence concerning:

The administered doses.
The patient’s pain condition.
The treatment response.
The relationship between the inhibitor and dextromethorphan exposure.
Whether adverse effects were unacceptable under the treatment context.

Claims 9 and 13: tinnitus and sexual dysfunction

Claim 9 covers treatment of tinnitus. Claim 13 covers treatment of sexual dysfunction and is narrowed by claim 14 to male patients with priapism or premature ejaculation.

These indications are separate claim categories. A product used for pain would not infringe claim 9 or claim 13 unless it was also used for tinnitus or sexual dysfunction.

Claim 13 is relatively broad in its independent form because it does not restrict sexual dysfunction to a particular sex, disease mechanism, or subtype. Claim 14 narrows the scope to male priapism or premature ejaculation.

What does the quinidine 300 mg limitation mean?

Claims 3, 7, 11, 16 and 21 limit quinidine to a dosage “not exceeding about 300 milligrams per day,” or, in claim 21, “300 milligrams/day or less.”

Claims	Condition	Quinidine limitation
3	Chronic or intractable pain	Not exceeding about 300 mg/day
7	Chronic or intractable pain	Not exceeding about 300 mg/day
11	Tinnitus	Not exceeding about 300 mg/day
16	Sexual dysfunction	Not exceeding about 300 mg/day
21	Oral unit-dose pain formulation	300 mg/day or less

The limitation applies to quinidine, not to quinine or the other listed inhibitors. A formulation using fluoxetine, propranolol, disulfiram or nortriptyline does not need to satisfy the quinidine dosage limitation, although it must satisfy the other elements of the relevant claim.

The word “about” in claims 3, 7, 11 and 16 creates a potential claim-construction issue around minor deviations from 300 mg/day. Claim 21 uses more exact language but still requires interpretation in the context of pharmaceutical dosing.

What formulations are protected by RE38115?

Claim 18 covers a unit dosage formulation for chronic or intractable pain containing:

Dextromethorphan or a pharmaceutically acceptable salt.
A debrisoquin hydroxylase inhibitor.
A combined form designed for oral ingestion by humans.
Dosages that make dextromethorphan therapeutically effective.
A therapeutic effect that substantially reduces pain without unacceptable side effects.

Claim 19 narrows the formulation to a digestible capsule enclosing both components. Claims 20 and 21 specify quinine or quinidine, with claim 21 limiting quinidine to 300 mg/day or less. Claim 22 covers the second inhibitor group.

What the formulation claims do not expressly require

Claim 18 does not expressly require:

A particular capsule size.
A fixed dextromethorphan-to-inhibitor ratio.
Immediate-release or extended-release delivery.
A specific excipient.
A particular salt of dextromethorphan.
A particular manufacturing process.
A branded product.
A specific pharmacokinetic profile.

The functional language remains important. A capsule containing both ingredients could still fall outside the claim if the combined dosage did not render dextromethorphan therapeutically effective for pain or did not substantially reduce pain.

When did RE38115 lose exclusivity?

RE38115 has expired. A US reissue patent generally inherits the remaining term of the original patent and does not restart the patent term clock. Public patent records identify the reissue as a reissue of the earlier dextromethorphan patent family, with the original term ending in approximately 2010. The reissue therefore does not provide a live US patent exclusion right today. [1][2]

Event	Approximate status
Original dextromethorphan patent family	Granted before the reissue
Reissue patent RE38115	Issued in 2003
Patent term	Derived from original patent
US expiration	Approximately 2010
Current enforceability	Expired

Because the patent has expired, a current generic or branded competitor does not need a license from the RE38115 patent owner to practice the expired claims. Historical assignments, licenses and enforcement activity remain relevant to the development of the dextromethorphan/quinidine market but do not restore the expired patent.

What is the Orange Book status of RE38115?

RE38115 is not a current Orange Book exclusivity barrier for Nuedexta or another approved dextromethorphan product.

The FDA Orange Book lists patents submitted by an NDA holder for an approved drug product. A historical patent can be absent from the current Orange Book because it has expired, was not listed for the relevant NDA, or was not directed to the approved product’s labeled indication or dosage form. Orange Book status must therefore be analyzed separately from general patent-family ownership. [3]

For Nuedexta, the commercial product is dextromethorphan hydrobromide and quinidine sulfate, approved for pseudobulbar affect. RE38115 principally addressed pain, tinnitus, sexual dysfunction and a pain formulation. The patent’s claim scope does not expressly cover pseudobulbar affect.

Which companies challenged or commercialized the dextromethorphan/quinidine combination?

The commercial dextromethorphan/quinidine market developed around Avanir Pharmaceuticals’ Nuedexta. Nuedexta received FDA approval in 2010 for pseudobulbar affect, not for the pain, tinnitus or sexual-dysfunction indications recited in RE38115. [4]

The relevant competitive groups include:

Participant	Role
Avanir Pharmaceuticals	Developer and commercial sponsor of Nuedexta
Otsuka Pharmaceutical	Acquired Avanir and continued commercial development
Generic drug manufacturers	Potential ANDA applicants for dextromethorphan/quinidine products
Earlier patent owners and licensors	Held or licensed rights in the dextromethorphan/CYP2D6 combination technology

The principal patent risk for a current dextromethorphan/quinidine entrant would arise from later patents directed to pseudobulbar affect, dosage ratios, formulations, pharmacokinetics, manufacturing and approved-product labeling, not from expired RE38115.

What Paragraph IV risks are associated with RE38115?

There is no current Paragraph IV exposure based solely on RE38115 because the patent has expired.

A Paragraph IV certification is relevant when an ANDA applicant seeks approval for a drug product referencing an NDA with listed patents and certifies that a listed patent is invalid, unenforceable or will not be infringed. An applicant could historically have challenged an unexpired patent such as RE38115 if it had been listed against the relevant reference product, but the patent’s expiration removes it as a current barrier. [5]

For modern dextromethorphan/quinidine products, Paragraph IV risk may instead involve later patents covering:

Pseudobulbar affect.
Specific dextromethorphan and quinidine ratios.
Modified-release tablets or capsules.
Stability and dissolution profiles.
Pharmacokinetic exposure.
Treatment regimens.
Methods of reducing adverse effects.

A generic applicant could avoid RE38115’s historical indication claims by pursuing a label that omits pain, tinnitus and sexual-dysfunction uses. That strategy would not eliminate risk from later patents with broader formulation or composition claims.

How does RE38115 compare with later Nuedexta patents?

Issue	RE38115	Later Nuedexta-related patents
Core combination	Dextromethorphan plus CYP2D6 inhibitor	Often dextromethorphan plus quinidine
Main indications	Pain, tinnitus, sexual dysfunction	Pseudobulbar affect and related treatment uses
Dosage specificity	Quinidine at or below about 300 mg/day in dependent claims	More product-specific dose, ratio or regimen claims may apply
Formulation	Oral combined unit dose for pain	Product-specific tablet, capsule, release or stability claims
Current term	Expired	Some later patents may have had terms extending into the 2020s or later
Current litigation value	Historical only	Potentially relevant to ANDA launch analysis

RE38115 is technically broad in its use of CYP2D6 inhibitor categories, but it is commercially weaker today because it is expired and does not target the approved Nuedexta indication. Later patents can be narrower technically while carrying greater commercial significance if they remain listed for an approved product.

How strong was the patent estate for RE38115?

The estate was strongest against a product or treatment that combined all of the following:

Dextromethorphan.
Quinidine or another named inhibitor.
A claimed therapeutic indication.
Oral co-administration or a combined capsule.
A dosage producing the stated functional result.

The estate was weaker where a competitor:

Used dextromethorphan alone.
Used an inhibitor outside the listed groups.
Treated an unclaimed indication.
Used separate products rather than a combined dosage form.
Challenged whether the treatment achieved the claimed therapeutic result.
Used a dosage outside the quinidine-dependent claims.

Today, the legal strength of RE38115 is effectively zero as an exclusion right because the patent term has ended. Its technical disclosures may remain relevant as prior art against later patent applications, particularly applications claiming dextromethorphan with quinidine for pain or other previously disclosed conditions.

What manufacturing and IP barriers remain?

RE38115 does not contain a meaningful manufacturing-process barrier. The formulation claims require a combined oral dosage form but do not claim a distinctive process, excipient system or release technology.

Current barriers may instead arise from:

Pharmaceutical-grade quinidine sourcing.
Control of the dextromethorphan-to-quinidine ratio.
Tablet or capsule stability.
Dissolution and bioequivalence.
CYP2D6-related pharmacokinetic variability.
FDA requirements for an ANDA or 505(b)(2) application.
Later formulation or method-of-use patents.
Product-specific labeling and risk-management requirements.

The principal regulatory challenge is demonstrating bioequivalence and acceptable safety for a combination in which quinidine changes dextromethorphan exposure. The expired RE38115 patent does not prevent such development.

Key Takeaways

RE38115 claims dextromethorphan combined with quinidine, quinine, disulfiram, fluoxetine, propranolol or nortriptyline.
The covered uses are chronic or intractable pain, tinnitus and sexual dysfunction.
Claim 18 covers an oral unit dosage formulation for pain, including a capsule under claim 19.
Several dependent claims limit quinidine to about 300 mg/day or less.
The claims use the historical term “debrisoquin hydroxylase inhibitor,” corresponding broadly to CYP2D6 inhibition.
RE38115 does not expressly claim pseudobulbar affect, the approved indication for Nuedexta.
The patent expired at the end of its original term, approximately in 2010.
It is not a current US exclusivity barrier or current Paragraph IV threat.
Current commercial risk must be evaluated against later Nuedexta-related patents, Orange Book listings and product-specific formulation claims.
RE38115 remains relevant as historical prior art and as evidence of early disclosure of dextromethorphan/CYP2D6-inhibitor combinations.

FAQs

Does RE38115 cover Nuedexta?

Not directly as an indication claim. Nuedexta contains dextromethorphan hydrobromide and quinidine sulfate, but RE38115’s principal indications are pain, tinnitus and sexual dysfunction. Nuedexta is approved for pseudobulbar affect.

Can a company launch a dextromethorphan/quinidine product without licensing RE38115?

Yes, RE38115 is expired. A launch still requires review of later patents, FDA requirements, Orange Book listings and applicable labeling restrictions.

Does RE38115 cover dextromethorphan and fluoxetine?

The claims expressly list fluoxetine as a qualifying inhibitor. The combination would need to satisfy the relevant indication, administration and therapeutic-effect limitations.

Is quinidine above 300 mg/day outside every RE38115 claim?

No. The 300 mg/day limitation appears in dependent claims directed to quinidine. The broader independent claims do not state that numeric ceiling, although they retain their other limitations.

Does a two-bottle regimen avoid the formulation claims?

It may avoid claims directed to a combined oral unit dosage formulation, such as claim 18, but it would not necessarily avoid the method claims. The method claims focus on administration of dextromethorphan with the inhibitor, not necessarily on a single capsule.

References

United States Patent and Trademark Office. (2003). Methods and compositions for treating pain and other conditions using dextromethorphan (U.S. Reissue Patent No. RE38,115).
Google Patents. (n.d.). U.S. RE38115E1: Methods and compositions for treating pain and other conditions using dextromethorphan.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations.
U.S. Food and Drug Administration. (2010). Nuedexta approval letter and prescribing information.
U.S. Food and Drug Administration. (2024). Abbreviated new drug application approvals and patent certifications.

PCT Information
PCT Filed	September 22, 1994	PCT Application Number:	PCT/US94/10771
PCT Publication Date:	March 28, 1996	PCT Publication Number:	WO96/09044

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	8071894	⤷ Start Trial
Germany	69434794	⤷ Start Trial
European Patent Office	0788359	⤷ Start Trial
European Patent Office	1634597	⤷ Start Trial
Spain	2268686	⤷ Start Trial
Japan	4097285	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: RE38115

Summary for Patent: RE38115