US Patent 9,399,036: Claim Scope, Expiration, Orange Book Status, Litigation Risk and Colchicine Patent Landscape

US Patent 9,399,036 covers specific methods of administering colchicine without dose reduction when the patient receives voriconazole, fluconazole, or cimetidine, each characterized as a CYP3A4 inhibitor that does not inhibit P-glycoprotein. The patent is a narrow method-of-use patent. It does not claim colchicine itself, a colchicine formulation, a fixed-dose combination, or the three interacting drugs.

The principal infringement risks arise from the required treatment sequence, colchicine dose range, named CYP3A4 inhibitor, and continued use of colchicine without dose adjustment. The patent’s nominal 20-year term is expected to run through December 21, 2027, subject to any patent-term adjustment shown in the USPTO record. The claims should be analyzed separately from FDA labeling, because the patented regimen may conflict with current colchicine prescribing restrictions for CYP3A4 inhibitors.

What does US Patent 9,399,036 cover?

US Patent 9,399,036 covers methods for administering colchicine during treatment with three specified drugs:

Element	Required limitation
Colchicine dose	About 0.6 to about 1.2 mg/day
Treatment purpose	General colchicine administration or prevention of gout flares
CYP3A4 drug	Voriconazole, fluconazole, or cimetidine
P-gp status	The second drug must not inhibit P-glycoprotein 1
Sequence	Either colchicine maintenance precedes the second drug, or the second drug precedes colchicine
Concomitant treatment	Colchicine and the second drug overlap
Dose adjustment	Colchicine continues without dose reduction or adjustment
Maintenance duration	A plurality of days; certain claims require at least seven days

The patent is directed to a drug-drug interaction management method. Its commercial relevance depends on whether a product label, clinical protocol, hospital order set, or physician practice directs the claimed sequence and dose.

The claims do not cover every CYP3A4 inhibitor. The named-drug limitation is central. A regimen involving ketoconazole, clarithromycin, itraconazole, erythromycin, ritonavir, or another CYP3A4 inhibitor is outside the literal scope of the claims unless another claim or doctrine of equivalents applies.

What are the independent claims in US 9,399,036?

Claims 1, 8, 9, and 10 are the principal independent claims.

Claims 1 and 8: colchicine first, inhibitor second

Claims 1 and 8 require:

A therapeutic fixed maintenance dose of colchicine of approximately 0.6 to 1.2 mg/day.
Administration for a maintenance period lasting multiple days.
Subsequent administration of voriconazole, fluconazole, or cimetidine.
Continued administration of the same colchicine dose during administration of the second drug.
No colchicine dose reduction.

Claim 8 adds prevention of gout flares as the treatment purpose. Claim 1 is broader because it covers administration of colchicine without expressly limiting the method to gout-flare prevention.

The sequence is material. A patient who begins voriconazole or fluconazole before colchicine maintenance may not satisfy claims 1 or 8, although claims 9 and 10 address the reverse sequence.

Claims 9 and 10: inhibitor first, colchicine second

Claims 9 and 10 require:

Administration of the CYP3A4 inhibitor for multiple days without colchicine.
Initiation of colchicine at 0.6 to 1.2 mg/day.
Concomitant administration of colchicine and the CYP3A4 inhibitor.
Discontinuation of the inhibitor.
Continued colchicine at the same dose without adjustment after inhibitor discontinuation.

Claim 10 limits the purpose to preventing gout flares. Claim 9 is not expressly restricted to gout-flare prevention.

These claims create a different infringement pathway. The patented sequence is not limited to maintaining colchicine during the interaction. It also covers continuing the same colchicine dose after the CYP3A4 inhibitor has been stopped.

How do dependent claims narrow the patent scope?

Claims 2 through 7 impose additional dose and timing limitations.

Claim	Additional limitation
2	Voriconazole at 200 to 400 mg/day
3	Fluconazole at 200 to 400 mg/day
4	Cimetidine at 800 to 1,600 mg/day
5	Colchicine fixed maintenance dose of 0.6 mg/day
6	Colchicine fixed maintenance dose of 1.2 mg/day
7	Maintenance period of at least seven days

Claims 2 through 4 are narrower than claim 1 because they specify second-drug doses. Claims 5 and 6 narrow the colchicine range to a precise daily dose. Claim 7 provides a measurable duration requirement that may be easier to apply in a clinical-record analysis than the phrase “plurality of days.”

The combination of claims 2, 3, or 4 with claims 5, 6, and 7 produces highly specific infringement scenarios. For example, a regimen involving 0.6 mg/day of colchicine for at least seven days followed by fluconazole at 200 to 400 mg/day, with no colchicine reduction during overlap, would fall within the narrow claim set if all other limitations are met.

What is the strongest claim construction for US 9,399,036?

The patent’s strongest construction is a narrow, sequence-based regimen claim rather than a broad pharmacology claim.

“Fixed maintenance dose”

“Fixed maintenance dose” requires more than a nominal prescription. The patient must receive a maintained colchicine dose within the claimed range. A regimen that uses alternating doses, intermittent dosing, dose escalation, or patient-specific reductions may fall outside this limitation.

“Without dose reduction” and “without dose adjustment”

These limitations are unusually important. The claims require the same colchicine maintenance dose to continue during the relevant interaction and, for claims 9 and 10, after inhibitor discontinuation.

A reduction from 1.2 mg/day to 0.6 mg/day would likely avoid a claim requiring continued administration of the original 1.2 mg/day dose. Temporary interruption may also create a noninfringement argument, depending on how the claim is construed and whether the interruption occurs during the required concomitant period.

“Concomitantly”

Concomitant administration ordinarily requires temporal overlap, not necessarily simultaneous ingestion. A regimen in which colchicine is taken in the morning and fluconazole at night could still present infringement risk if both are administered during overlapping treatment periods.

“Not an inhibitor of P-gp”

The claim requires the second drug to be a CYP3A4 inhibitor but not a P-gp inhibitor. This limitation creates technical and litigation questions because enzyme and transporter classifications can depend on assay methodology, concentration, regulatory source, and date.

A defendant may challenge whether a listed drug meets the required pharmacological classification. The named-drug limitation does not eliminate this issue because the claim separately requires the drug to satisfy both CYP3A4 and P-gp characteristics.

What patents protect colchicine and Colcrys in the United States?

The colchicine estate is broader than US 9,399,036 and includes product, formulation, method-of-use, and interaction-management patents.

Patent category	Typical subject matter	Relevance to 9,399,036
Active ingredient	Colchicine itself	Limited because colchicine is an old compound
Product formulation	Tablets, strength, dissolution, purity, and dosage forms	Separate from the interaction regimen
Method of use	Gout-flare treatment or prophylaxis; familial Mediterranean fever	May overlap commercially with claim 8 or 10
Drug interaction	Colchicine administration with CYP3A4 or P-gp inhibitors	Closest technical category
Manufacturing	Purification, crystallization, formulation, and process controls	Can create supply-chain barriers without directly covering clinical use

Colcrys is colchicine marketed by Takeda Pharmaceuticals U.S.A., Inc., following Takeda’s acquisition of URL Pharma. The FDA-approved product is an oral colchicine tablet indicated for treatment of gout flares and prophylaxis of gout flares in adults, as well as familial Mediterranean fever in adults and children at least four years old, subject to the approved labeling [2].

US 9,399,036 is narrower than a basic Colcrys product patent because it requires a particular interacting drug and dosing sequence. A generic colchicine manufacturer could avoid this patent while still facing separate Orange Book-listed formulation or method-of-use patents.

What is the patent expiration date for US 9,399,036?

The patent’s nominal expiration is December 21, 2027, based on the earliest reported nonprovisional priority date of December 21, 2007 and the standard 20-year US patent term under 35 U.S.C. § 154.

The effective expiration date can differ if the patent has:

Patent-term adjustment for USPTO delay.
Patent-term extension for regulatory review.
Terminal disclaimer tied to another patent.
A corrected term calculation in the USPTO patent record.

The patent issued July 26, 2016. Its remaining term at issuance was therefore approximately 11 years before accounting for any adjustment. A patent-term extension is unlikely for this type of method patent unless the statutory regulatory requirements were satisfied.

What is the Orange Book status of US 9,399,036?

The Orange Book is the controlling FDA source for patents submitted for an approved drug product. Patent ownership, Google Patents records, and product labeling do not independently establish Orange Book listing status.

If US 9,399,036 is listed for Colcrys, its commercial effect would depend on the associated use code. A method patent directed to colchicine administration with named CYP3A4 inhibitors may be listed with a use code covering a specific drug interaction or gout-prophylaxis method. A generic applicant could respond through:

Paragraph III certification, accepting delay until patent expiration.
Paragraph IV certification, asserting invalidity, unenforceability, or noninfringement.
A section viii statement, carving out a patented method of use from the proposed label.

The patent’s limited named-drug scope creates a potential section viii pathway if the generic label omits the patented interacting-drug regimen. That pathway depends on the Orange Book use code and the wording of the proposed generic label. A paragraph IV filing would create greater litigation exposure but could preserve a broader label.

The FDA label for colchicine contains strong warnings regarding coadministration with P-gp and CYP3A4 inhibitors and recommends dose modification or avoidance in specified circumstances [2]. This regulatory context may make a commercial label less likely to instruct the claimed no-reduction regimen, even if the patent claims cover it.

When does colchicine lose exclusivity?

Colchicine lost basic compound exclusivity long before the approval of Colcrys. The commercial exclusivity relied on FDA approval, product-specific patents, formulation protection, and method-of-use rights.

Exclusivity type	Status
Original colchicine compound	Expired
FDA approval exclusivity for modern colchicine product	Expired
Product and formulation patents	Expiration dates vary by patent
US 9,399,036	Nominally expires December 21, 2027
Generic entry	Depends on remaining Orange Book patents, certifications, litigation, and label design

The practical generic-entry date is therefore not determined by US 9,399,036 alone. A generic applicant must assess every unexpired Orange Book patent listed against the relevant colchicine product.

Which companies are challenging the colchicine patent estate?

Generic competition has involved manufacturers seeking approval for colchicine products, including manufacturers such as Hikma, Amneal, West-Ward, Watson/Actavis, and other abbreviated new drug application sponsors over time. The relevant challenger depends on the specific NDA, ANDA, patent listing, certification, and litigation docket.

US 9,399,036 should not be treated as a standalone barrier to generic colchicine. A challenger can target the patent through:

A paragraph IV certification.
A section viii carve-out.
A noninfringing label that omits voriconazole, fluconazole, or cimetidine use.
An invalidity challenge based on anticipation or obviousness.
A factual challenge to the CYP3A4/P-gp classification.
A challenge to the “fixed maintenance dose” or “without dose adjustment” limitations.

No conclusion about a specific company’s current challenge follows from the patent claims alone. The relevant legal record is the FDA Orange Book entry, the ANDA notice letter, and any resulting district-court or Federal Circuit docket [1, 3].

How strong is the patent estate for US 9,399,036?

Strengths

The patent has several features that can support enforcement:

The claims require a defined dose range.
They identify three specific interacting drugs.
They require a defined treatment sequence.
Claims 5 through 7 provide concrete dependent limitations.
The no-dose-reduction limitation can be tied to medication records.
Claims 8 and 10 target gout-flare prevention, a central colchicine use.

The patent may be particularly relevant where a branded or generic label expressly recommends maintaining colchicine at 0.6 or 1.2 mg/day during treatment with one of the named drugs.

Weaknesses

The claims also have material vulnerabilities:

The named-drug list is narrow.
The claims depend on pharmacological classifications that may be disputed.
“Therapeutically effective,” “plurality of days,” and “concomitantly” may invite construction disputes.
The no-dose-reduction regimen may conflict with FDA-approved colchicine safety warnings.
A generic label may omit the patented interaction and pursue approval for noninfringing uses.
The underlying concept of CYP3A4-mediated colchicine interaction may be vulnerable to obviousness arguments if prior art disclosed colchicine dose adjustment or avoidance with CYP3A4 inhibitors.

The patent is stronger against direct instructions to follow the claimed regimen than against ordinary prescribing in which a physician independently selects colchicine and an antifungal drug for separate indications.

What patent litigation affects US 9,399,036?

The relevant litigation questions are:

Issue	Business impact
Paragraph IV notice	May trigger a 30-month FDA approval stay under Hatch-Waxman
Claim construction	Determines whether actual labels and treatment records meet the sequence limitations
Induced infringement	Depends on label instructions, promotional conduct, and physician behavior
Section viii carve-out	Can permit approval for unpatented colchicine uses
Invalidity	Obviousness and written-description defenses are central
Settlement	Could defer generic launch beyond patent expiration or permit an earlier licensed entry
Orange Book delisting	Could remove a regulatory obstacle but would not erase all private litigation risk

A settlement agreement involving this patent would need to be reviewed for entry date, authorized generic terms, supply rights, geographic restrictions, and any FTC reporting or antitrust issues. The patent number alone does not establish that a settlement exists or remains operative.

What geographic coverage does US 9,399,036 provide?

US 9,399,036 provides rights only in the United States and its territories. It cannot directly block:

Use of the regimen entirely outside the United States.
Foreign manufacture that does not implicate US importation.
Foreign prescribing or dispensing.
Non-US regulatory approval.

Foreign counterparts, if any, must be assessed independently. Patent term, claim language, examination history, compulsory-license rules, and national regulatory labeling differ by country.

What generic launch scenarios exist for colchicine?

Early launch after successful paragraph IV litigation

A generic could launch before nominal patent expiration if it establishes invalidity or noninfringement and no other Orange Book patent blocks approval.

Section viii launch

A generic may seek approval for gout treatment or other uses while omitting the patented CYP3A4-inhibitor regimen. This is the most direct design-around strategy if the use code is sufficiently narrow.

At-risk launch

A manufacturer could launch before final resolution of litigation, accepting possible damages and injunctive exposure. The commercial decision would depend on market size, expected damages, remaining patent term, and the number of competing ANDAs.

Post-expiration launch

A launch after December 2027 would still require review of any other unexpired product or formulation patents and any pediatric or regulatory exclusivity.

How does US 9,399,036 compare with formulation and method-of-use patents?

US 9,399,036 is a regimen patent. It differs from formulation patents in three ways:

It does not require a particular tablet composition.
It does not require a specific release profile, excipient, particle size, or manufacturing process.
Infringement depends on patient treatment conduct rather than product manufacture and sale alone.

It also differs from broader method-of-use patents because it requires the named interacting drug, the colchicine maintenance range, overlapping administration, and continued dosing without adjustment.

For licensing and litigation valuation, the patent is therefore more dependent on labeling and clinical practice than a composition or formulation patent. Its value is highest if the patent holder controls or influences treatment protocols that expressly direct the claimed regimen.

Key Takeaways

US 9,399,036 is a narrow US method-of-use patent covering colchicine administration with voriconazole, fluconazole, or cimetidine.
The core requirement is continued colchicine at approximately 0.6 to 1.2 mg/day without dose reduction or adjustment.
Claims 1 and 8 cover colchicine maintenance followed by the inhibitor; claims 9 and 10 cover inhibitor pretreatment followed by colchicine and continued dosing after inhibitor discontinuation.
Claims 8 and 10 are limited to preventing gout flares.
Claims 2 through 7 narrow the scope by specifying drug doses, colchicine doses, and a seven-day maintenance period.
The patent does not claim colchicine, Colcrys, a fixed-dose combination, or all CYP3A4 inhibitors.
The nominal patent expiration date is December 21, 2027, subject to USPTO term adjustments.
Generic applicants may pursue paragraph IV, section viii, or label-design strategies.
FDA colchicine warnings concerning CYP3A4 and P-gp interactions may complicate commercial implementation of the patented no-reduction regimen.
The patent’s practical value depends heavily on Orange Book listing, use-code breadth, generic labels, clinical instructions, and any related litigation or settlement.

FAQs

Can a generic colchicine product infringe US 9,399,036 without naming voriconazole, fluconazole, or cimetidine?

Potentially, but infringement would require proof that the claimed regimen is induced or otherwise practiced. A generic label that omits the patented interaction reduces induced-infringement risk and may support a section viii strategy.

Does US 9,399,036 cover colchicine use with itraconazole or clarithromycin?

No, not literally based on the supplied claims. The claims identify voriconazole, fluconazole, and cimetidine. Other CYP3A4 inhibitors would require a different claim theory.

Does continuing colchicine after stopping fluconazole create infringement risk?

It can under claims 9 and 10 if the patient first received fluconazole for multiple days without colchicine, then received colchicine and fluconazole together, and continued the same fixed colchicine dose after fluconazole was discontinued.

Are physicians automatically liable for prescribing the claimed colchicine regimen?

No automatic liability follows from a prescription. Method-of-treatment enforcement would depend on claim construction, direct infringement evidence, inducement, statutory defenses, and the facts surrounding the prescribing and administration.

Can a formulation patent block generic colchicine after US 9,399,036 expires?

Yes. A separate unexpired Orange Book-listed formulation or method-of-use patent can delay or complicate generic approval even after the expiration of US 9,399,036.

References

U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book.
U.S. Food and Drug Administration. (2023). Colcrys (colchicine) prescribing information. Takeda Pharmaceuticals U.S.A., Inc.
U.S. Patent and Trademark Office. (2016). U.S. Patent No. 9,399,036, methods of administering colchicine with CYP3A4 inhibitors.
U.S. Code, 35 U.S.C. § 154. Patent term.
U.S. Code, 21 U.S.C. § 355(j). Abbreviated applications and patent certifications.

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Hikma Intl Pharms	MITIGARE	colchicine	CAPSULE;ORAL	204820-001	Sep 26, 2014	AB	RX	Yes	Yes	⤷ Start Trial	⤷ Start Trial				METHOD OF USING COLCHICINE FOR THE PROPHYLAXIS OF GOUT FLARES	⤷ Start Trial
>Applicant	>Tradename	>Generic Name	>Dosage	>NDA	>Approval Date	>TE	>Type	>RLD	>RS	>Patent No.	>Patent Expiration	>Product	>Substance	>Delist Req.	>Patented / Exclusive Use	>Submissiondate

Details for Patent: 9,399,036

Which drugs does patent 9,399,036 protect, and when does it expire?

Summary for Patent: 9,399,036