United States Drug Patent 5,166,207: Scope, Claims, Expiration, and Patent Landscape for Dextromethorphan-Quinidine

United States Patent No. 5,166,207 protected a method of increasing dextromethorphan exposure by coadministering a cytochrome P450IID6, now generally designated CYP2D6, inhibitor. Quinidine is the expressly claimed inhibitor. The patent covered neuroprotective treatment concepts involving ischemia, hypoxia, hypoglycemia, epilepsy, Huntington's disease, Alzheimer's disease, and amyotrophic lateral sclerosis.

The patent issued on November 24, 1992. Because it was filed before the 1995 patent-term transition, its ordinary 17-year term from issuance ended on November 24, 2009. It is therefore expired and cannot block current generic, reformulation, or therapeutic use of dextromethorphan-quinidine. Its technical disclosure remains relevant because it established the pharmacokinetic rationale later used in Nuedexta, but the patent does not provide current exclusivity. [1][2]

What does United States Patent 5,166,207 cover?

Patent 5,166,207 covers a treatment method with two required components:

Dextromethorphan.
A CYP2D6 inhibitor administered in an amount sufficient to block or materially inhibit dextromethorphan metabolism.

The therapeutic objective is enhanced systemic delivery of dextromethorphan for specified neurological disorders. The patent is a method-of-treatment patent, not a composition-of-matter patent covering dextromethorphan, quinidine, or their salts.

Patent attribute	Details
U.S. patent	5,166,207
Patent title	Method for enhancing the systemic delivery of dextromethorphan
Issue date	November 24, 1992
Technology	CYP2D6 inhibition to increase dextromethorphan systemic exposure
Principal inhibitor identified in claims	Quinidine
Therapeutic field	Neuroprotection and neurological disorders
Claim type	Method of treatment
Ordinary expiration	November 24, 2009
Current blocking status	Expired
FDA regulatory exclusivity	None currently derived from this patent
Biosimilar relevance	None; dextromethorphan-quinidine is a small-molecule product

The patent’s commercial significance came from the pharmacokinetic interaction. Dextromethorphan is extensively metabolized by CYP2D6 to dextrorphan. Quinidine inhibits CYP2D6 and increases dextromethorphan concentrations. The patent sought to use that interaction to improve systemic delivery for neurological indications. [1][3]

What are the claims of Patent 5,166,207?

Claim 1: Broad neurological-injury method

Claim 1 requires:

a patient suffering from a neurological disorder resulting in injury to nervous tissue;
administration of a CYP2D6 inhibitor;
an inhibitor amount sufficient to block dextromethorphan metabolism; and
administration of dextromethorphan in an amount sufficient to treat the disorder.

The claim is broad as to the inhibitor. It does not limit the inhibitor to quinidine. A product or treatment could fall within the literal scope of claim 1 if it used another CYP2D6 inhibitor and met the therapeutic and pharmacokinetic limitations.

The claim is narrower than a general claim to administering dextromethorphan for any neurological disorder. It requires a disorder involving injury to nervous tissue and requires the inhibitor to be used for the stated metabolic purpose.

Claim 2: Quinidine limitation

Claim 2 depends from claim 1 and narrows the inhibitor to quinidine. This claim is the closest historical claim to the later dextromethorphan-quinidine product concept.

The claim does not specify:

a dextromethorphan-to-quinidine ratio;
a particular salt;
a fixed dose;
an immediate-release or extended-release formulation;
a daily dosing schedule;
a tablet or capsule;
treatment of pseudobulbar affect; or
a particular pharmacokinetic exposure target.

Claim 3: Listed neurological disorders

Claim 3 depends from claim 1 and identifies disorders resulting from:

ischemia;
hypoxia;
hypoglycemia;
epilepsy;
Huntington's disease;
Alzheimer's disease; or
amyotrophic lateral sclerosis.

The dependent claim narrows the disorder limitation but does not narrow the inhibitor to quinidine. A treatment using another qualifying CYP2D6 inhibitor could theoretically fall within claim 3 if the remaining limitations were satisfied.

Claim 4: Endogenous excitatory amino-acid disorders

Claim 4 creates a separate independent method claim. It requires a neurological disorder mediated by an endogenous excitatory amino acid rather than expressly requiring a disorder that results in injury to nervous tissue.

This language is directed to excitotoxicity. The claim is potentially broader in disease theory because it does not use the exact "injury to nervous tissue" formulation in claim 1. It still requires:

a CYP2D6 inhibitor;
an amount sufficient to block dextromethorphan metabolism; and
an amount of dextromethorphan sufficient to treat the disorder.

Claim 5: Quinidine under claim 4

Claim 5 limits claim 4 to quinidine. It is the claim 4 counterpart to claim 2.

Claim 6: Listed disorders under claim 4

Claim 6 limits claim 4 to ischemia, hypoxia, hypoglycemia, epilepsy, Huntington's disease, Alzheimer's disease, or amyotrophic lateral sclerosis.

How broad is the claim scope?

The patent’s claim scope is functional and method-oriented. It turns on what the administered amounts do, not merely on the identity of the ingredients.

Functional inhibitor limitation

The phrase "an amount ... sufficient to block dextromethorphan metabolism" requires a functional showing. A claimant would need to establish that the inhibitor materially inhibited the relevant CYP2D6 metabolism under the treatment conditions.

The claims do not expressly require complete inhibition. "Block" could be argued to mean substantial inhibition rather than total elimination of metabolism. The scope would depend on claim construction, specification evidence, pharmacokinetic data, and the accused regimen.

Functional dextromethorphan limitation

The amount of dextromethorphan must be "sufficient to treat" the neurological disorder. This limitation creates a treatment-efficacy requirement. Mere coadministration of dextromethorphan and quinidine would not automatically satisfy the claim if the regimen was not administered for treatment of a covered disorder or did not provide a therapeutically sufficient amount.

Required coadministration

The patent requires administration of both agents to the patient. A claim infringement analysis would focus on the labeled or actual treatment regimen, including whether the CYP2D6 inhibitor and dextromethorphan were administered as part of the same therapeutic method.

The patent does not claim a CYP2D6 inhibitor alone, dextromethorphan alone, or a diagnostic method based on CYP2D6 genotype.

No express ratio or dosage limitation

The absence of fixed doses and ratios increases the literal breadth of the claims. It also creates potential vulnerability in an enforcement case because the patentee would need to show that the accused amounts satisfy the functional limitations.

What diseases are covered by Patent 5,166,207?

The claims identify seven disease categories:

Disease or condition	Claim 3	Claim 6
Ischemia	Yes	Yes
Hypoxia	Yes	Yes
Hypoglycemia	Yes	Yes
Epilepsy	Yes	Yes
Huntington's disease	Yes	Yes
Alzheimer's disease	Yes	Yes
Amyotrophic lateral sclerosis	Yes	Yes

Claims 1 and 3 are framed around neurological disorders resulting in nervous-tissue injury. Claims 4 and 6 are framed around disorders mediated by endogenous excitatory amino acids.

The claims do not expressly cover pseudobulbar affect. That indication became central to Nuedexta, but Nuedexta’s commercial protection rests on later patents, regulatory exclusivity, and product-specific labeling rather than on the expired 1992 patent. [3][4]

When did Patent 5,166,207 lose exclusivity?

Patent 5,166,207 lost patent exclusivity on November 24, 2009, based on the ordinary 17-year term applicable to a pre-June 8, 1995 patent application issued on November 24, 1992. The patent therefore expired before FDA approval of Nuedexta in 2010.

Event	Date
Patent issued	November 24, 1992
Ordinary 17-year expiration	November 24, 2009
Nuedexta FDA approval	October 29, 2010
Nuedexta orphan-drug exclusivity	Approximately seven years from approval, ending in 2017
Current status of Patent 5,166,207	Expired

The patent did not receive the type of current patent-term-extension value associated with a later-approved product. Its expiration predates Nuedexta’s approval, so it could not have delayed Nuedexta approval or created post-approval patent exclusivity.

What is the Orange Book status of Patent 5,166,207?

Patent 5,166,207 is not a current blocking Orange Book patent for Nuedexta. The patent had expired before Nuedexta was approved and is not a current source of listed patent protection.

The FDA Orange Book is relevant to later dextromethorphan-quinidine patents, particularly patents associated with the approved Nuedexta product and its labeled use. Orange Book listing is product-specific and does not revive an expired patent or convert an old method patent into a current regulatory barrier. [4]

The distinction is important:

Patent 5,166,207: historical technology patent, expired in 2009.
Nuedexta exclusivity: later product and indication protection.
Orange Book patents: later patents listed against the approved product, subject to FDA listing rules.
Orphan exclusivity: regulatory exclusivity, separate from patent rights.

How does Patent 5,166,207 relate to Nuedexta?

Nuedexta contains dextromethorphan hydrobromide and quinidine sulfate. The approved product uses quinidine at a low dose to inhibit CYP2D6 metabolism and increase dextromethorphan exposure. The commercial product therefore reflects the core pharmacokinetic concept described in Patent 5,166,207. [3]

The patent did not, however, protect the full modern Nuedexta product architecture. It did not claim:

the specific 20 mg dextromethorphan hydrobromide and 10 mg quinidine sulfate strength;
the Nuedexta capsule formulation;
the pseudobulbar-affect indication;
the approved dosing schedule;
the commercial brand;
manufacturing specifications; or
later pharmacokinetic or formulation refinements.

Later Nuedexta patents addressed some of those product-specific features. Their enforceability and expiration dates must be analyzed separately from Patent 5,166,207. [4][5]

What later patents protect dextromethorphan-quinidine products?

The later patent landscape generally falls into four categories.

Composition and dosage-form patents

These patents may cover combinations of dextromethorphan and quinidine, including particular salt forms, strength combinations, ratios, or dosage forms. They are more commercially relevant to generic applicants seeking to market a product equivalent to Nuedexta.

Method-of-use patents

Later patents may cover treatment of pseudobulbar affect or other specified neurological conditions. A method patent can create risk where a generic label directly instructs the claimed use, even if the active ingredients are old.

Pharmacokinetic patents

These patents may claim exposure ranges, metabolic inhibition levels, or dosing relationships designed to maintain dextromethorphan concentrations while limiting quinidine exposure.

Manufacturing and formulation patents

Patents may protect excipient systems, capsule compositions, stability profiles, particle characteristics, blend processes, or scalable manufacturing methods. These patents generally do not prevent all dextromethorphan-quinidine products, but they can constrain a commercially practical formulation.

The key business point is that Patent 5,166,207 is no longer the relevant barrier. Current risk would arise from later unexpired patents, regulatory exclusivity, and litigation involving the approved product.

Are Paragraph IV challenges relevant to Patent 5,166,207?

A Paragraph IV challenge to Patent 5,166,207 would have no current commercial purpose because the patent expired in 2009. An ANDA applicant could not use a Paragraph IV certification to create meaningful entry timing against an expired patent.

For later Nuedexta patents, an ANDA applicant may use:

Paragraph I certification if no patent information is listed;
Paragraph II certification if the listed patent has expired;
Paragraph III certification with a post-expiration launch date; or
Paragraph IV certification asserting that the listed patent is invalid, unenforceable, or not infringed.

A Paragraph IV filing can trigger patent litigation under Hatch-Waxman. The litigation can delay approval through the statutory 30-month stay, subject to statutory exceptions and court action. [6]

Which companies have challenged dextromethorphan-quinidine exclusivity?

Generic competition to Nuedexta has centered on ANDA applicants challenging later product patents, not on Patent 5,166,207. Public records should be reviewed for each applicant, patent number, complaint date, settlement, and launch restriction before making an investment or litigation decision.

The competitive field includes:

Avanir Pharmaceuticals, the original Nuedexta developer;
Otsuka Pharmaceutical, which acquired Avanir;
generic pharmaceutical companies pursuing ANDA approval;
specialty-pharma companies evaluating alternative dextromethorphan formulations; and
developers of therapies for pseudobulbar affect and related neurological symptoms.

No biosimilar pathway applies. Nuedexta is a small-molecule combination product regulated through the ANDA framework, not a biologics license application and biosimilar pathway.

What generic entry risks exist for dextromethorphan-quinidine?

The expired 1992 patent creates no generic-entry risk. The principal remaining risks historically associated with a Nuedexta generic would have been:

Risk category	Relevance
Expired core method patent	No current barrier
Later composition patents	Potentially significant
Later formulation patents	Depends on the proposed dosage form
Method-of-use patents	Depends on the ANDA label and carve-out strategy
Orphan exclusivity	Ended in 2017
Regulatory exclusivity	Must be checked against current FDA records
Patent litigation	Depends on listed patents and ANDA timing
Manufacturing patents	May affect supply economics rather than market entry
Biosimilar substitution risk	Not applicable
Induced infringement	Possible issue for labeled use claims under later patents

A generic applicant could seek approval after addressing any currently listed, unexpired patents. Because the foundational CYP2D6-inhibition concept is public and the patent is expired, a later patent would need to claim a narrower product, formulation, dosing regimen, indication, or manufacturing feature.

How strong is the patent estate associated with Patent 5,166,207?

The estate has strong historical significance but no current exclusionary strength.

Strength factor	Assessment
Core mechanism	Public and technically important
Claim breadth	Broad functional method claims
Express quinidine coverage	Yes
Fixed formulation protection	No
Fixed dosage protection	No
Pseudobulbar-affect claim	No express claim in the provided claims
Current validity	Expired
Current enforcement value	None
Prior-art value	High
Freedom-to-operate value today	Generally favorable as to this patent alone

The claims would have had meaningful reach during their term because they covered functional coadministration of a CYP2D6 inhibitor and dextromethorphan across multiple neurological disorders. Their weakness today is temporal rather than primarily technical: the statutory term has ended.

What litigation or settlement agreements affect Patent 5,166,207?

Patent 5,166,207 itself is not a current litigation barrier. Any historical litigation involving dextromethorphan-quinidine products must be distinguished from later disputes over Nuedexta patents.

Settlements involving later patents may include:

delayed generic launch dates;
licenses to specific patent claims;
authorized-generic arrangements;
restrictions on labeled indications;
covenants not to sue; or
dismissal after an ANDA amendment.

A settlement concerning a later Nuedexta patent would not extend Patent 5,166,207 or restore its exclusivity. The FDA and Federal Trade Commission have treated Hatch-Waxman settlements as fact-specific agreements requiring review for launch restrictions and potential antitrust concerns. [6][7]

What geographic coverage does Patent 5,166,207 provide?

The patent is a United States patent. Its claims apply only to conduct within the United States or conduct that falls within U.S. patent infringement statutes, including certain imports or activities involving products made by patented processes where applicable.

Foreign protection would require separate national or regional patents. The U.S. patent does not establish protection in:

Canada;
Europe;
Japan;
China;
Australia; or
other jurisdictions.

Because the U.S. patent expired in 2009, geographic freedom to operate in the United States is not presently restricted by this patent. Foreign patent status would need to be evaluated separately within each national family member.

What manufacturing and intellectual-property barriers remain?

Patent 5,166,207 does not claim a manufacturing process. It does not prevent production of:

dextromethorphan;
quinidine;
their pharmaceutical salts;
a combination product; or
an alternative formulation.

Current manufacturing barriers, if any, would come from later process patents, proprietary know-how, controlled-substance handling requirements, analytical methods, supply constraints, or regulatory requirements for demonstrating pharmaceutical equivalence.

For an ANDA applicant, the practical barriers are more likely to involve bioequivalence, formulation matching, capsule or tablet performance, stability, API sourcing, and the scope of later listed patents than the expired 1992 patent.

Key Takeaways

Patent 5,166,207 covers coadministration of dextromethorphan with a CYP2D6 inhibitor to increase systemic dextromethorphan delivery.
Quinidine is expressly claimed in dependent claims 2 and 5.
The disease categories include ischemia, hypoxia, hypoglycemia, epilepsy, Huntington's disease, Alzheimer's disease, and ALS.
The patent is a method-of-treatment patent, not a composition, formulation, or manufacturing patent.
Its ordinary patent term ended on November 24, 2009.
It was expired before FDA approval of Nuedexta in October 2010.
It is not a current Orange Book barrier for Nuedexta.
It does not expressly claim pseudobulbar affect, the Nuedexta 20 mg/10 mg strength, or the marketed capsule.
No biosimilar pathway applies because the product is a small-molecule drug.
Current market-entry analysis must focus on later Nuedexta patents, FDA listing data, ANDA certifications, litigation, settlements, and any formulation or manufacturing patents.

FAQs About U.S. Patent 5,166,207

Does Patent 5,166,207 cover Nuedexta?

It covers the underlying concept of using quinidine to inhibit CYP2D6 metabolism and increase systemic dextromethorphan delivery, but it expired before Nuedexta approval and does not provide current protection for Nuedexta.

Did Patent 5,166,207 claim pseudobulbar affect?

No. The provided claims identify neurological injury and excitatory-amino-acid-mediated disorders, with specified examples. They do not expressly identify pseudobulbar affect.

Can a generic company rely on the expired patent to launch dextromethorphan-quinidine?

The expired patent does not block launch. A generic applicant must still address any later unexpired patents listed for the reference product and satisfy FDA ANDA requirements.

Is quinidine required for every claim?

No. Claims 1, 3, 4, and 6 broadly refer to a CYP2D6 inhibitor. Claims 2 and 5 specifically limit the inhibitor to quinidine.

Does the patent cover all CYP2D6 inhibitors?

The independent claims are not limited to quinidine, but the inhibitor must be a CYP2D6 inhibitor used in an amount sufficient to block dextromethorphan metabolism. The claims do not automatically cover every compound alleged to affect CYP2D6.

References

United States Patent and Trademark Office. (1992). U.S. Patent No. 5,166,207: Method for enhancing the systemic delivery of dextromethorphan.
U.S. Code, 35 U.S.C. §§ 154, 156.
U.S. Food and Drug Administration. (2010). Nuedexta (dextromethorphan hydrobromide and quinidine sulfate) prescribing information.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations, commonly known as the Orange Book.
U.S. Patent and Trademark Office. (2024). Patent Center and Patent Examination Data System records for dextromethorphan-quinidine patent families.
Drug Price Competition and Patent Term Restoration Act of 1984, 21 U.S.C. § 355(j).
Federal Trade Commission. (2013). Agreements filed with the Federal Trade Commission under the Medicare Prescription Drug, Improvement, and Modernization Act of 2003.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Canada	2114267	⤷ Start Trial
Canada	2712821	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Summary for Patent: 5,166,207