U.S. Patent 8,927,607: Scope, Claims, Expiration, Orange Book Status, and Colchicine Patent Landscape

U.S. Patent No. 8,927,607 protects specific treatment sequences involving colchicine and three CYP3A4 inhibitors: voriconazole, fluconazole, and cimetidine. The claims do not cover colchicine itself, the listed inhibitors as compositions, or all colchicine-drug interactions. They cover administering unchanged maintenance-dose colchicine during, or after, treatment with one of those inhibitors for chronic gout, familial Mediterranean fever, or Behçet's disease.

The principal commercial risk is method-of-treatment infringement by a branded or generic colchicine manufacturer that induces use of the claimed dosing sequence. The patent is materially narrower than a conventional composition-of-matter or formulation patent because infringement depends on the patient's treatment sequence, drug identity, dose, disease, and absence of colchicine dose reduction.

What does U.S. Patent 8,927,607 protect?

The patent contains two independent claim structures.

Claim group	Required treatment sequence	Principal limitation
Claims 1-12	Colchicine maintenance therapy first, followed by a CYP3A4 inhibitor	Colchicine must continue at the same 0.6-1.2 mg/day dose without reduction
Claims 13-17	CYP3A4 inhibitor first, colchicine added during inhibitor therapy, then inhibitor stopped	Colchicine continues at the same fixed dose after inhibitor discontinuation

The listed CYP3A4 inhibitors are limited to:

Voriconazole.
Fluconazole.
Cimetidine.

The claims also require that the inhibitor not be an inhibitor of P-glycoprotein 1, or P-gp. The disease limitation is equally important. The claimed inflammatory disorders are:

Chronic gout.
Familial Mediterranean fever.
Behçet's disease.

The patent therefore does not cover every patient receiving colchicine with a CYP3A4 inhibitor. A potentially infringing regimen must satisfy the claimed drug, disease, dose, sequence, and duration limitations.

How do claims 1 through 12 operate?

Claims 1 through 12 cover the situation in which the patient is already receiving colchicine and later begins the CYP3A4 inhibitor.

The required sequence is:

The patient receives a therapeutically effective fixed maintenance dose of colchicine.
The colchicine dose is administered for several days, with claim 8 specifying at least seven days.
The second drug is introduced.
The same colchicine dose continues during administration of the second drug.
The colchicine dose is not reduced.

The base dose range is about 0.6 to about 1.2 mg/day. Dependent claims narrow that range to:

0.6 mg/day, under claim 5.
1.2 mg/day, under claim 6.

Claims 2 through 4 add inhibitor-specific dose ranges:

Inhibitor	Claimed dose
Voriconazole	200-400 mg/day
Fluconazole	200-400 mg/day
Cimetidine	800-1,600 mg/day

Claims 9 through 12 create narrower chronic-gout and voriconazole combinations. They cover both 0.6 mg/day and 1.2 mg/day colchicine regimens, with or without the 200-400 mg/day voriconazole limitation.

What is the commercial significance of the “without dose reduction” limitation?

The “without dose reduction” language is the central limitation in claims 1 through 12. A regimen that reduces colchicine when the inhibitor is introduced may avoid literal infringement of the asserted claim, depending on the exact instruction and treatment conduct.

A label that expressly instructs physicians to continue 0.6 mg/day or 1.2 mg/day during voriconazole, fluconazole, or cimetidine exposure would create a stronger inducement theory. A label that instructs dose interruption, dose reduction, or avoidance would reduce literal infringement risk, although the facts would still determine whether another theory applies.

How do claims 13 through 17 differ?

Claims 13 through 17 reverse the treatment sequence.

The claimed sequence is:

The patient receives the CYP3A4 inhibitor for several days without colchicine.
Colchicine is then introduced at a fixed maintenance dose of about 0.6-1.2 mg/day.
The inhibitor continues while colchicine is administered.
The inhibitor is discontinued.
The same fixed colchicine dose continues without adjustment.

This structure is narrower in sequencing but potentially important for hospitalized patients or patients who begin antifungal or acid-suppression therapy before colchicine.

Claims 14 through 17 focus on chronic gout and voriconazole. Claims 15 and 17 add the 200-400 mg/day voriconazole dose range.

The two independent claims therefore address opposite clinical scenarios:

Issue	Claims 1-12	Claims 13-17
First drug in sequence	Colchicine	CYP3A4 inhibitor
Second drug introduced	CYP3A4 inhibitor	Colchicine
Post-interaction requirement	Colchicine continues unchanged	Colchicine continues unchanged after inhibitor stops
Core risk	Dose maintained during inhibitor therapy	Dose maintained after inhibitor therapy

What patent claims are not covered by U.S. Patent 8,927,607?

The patent does not claim:

Colchicine as a chemical compound.
A colchicine tablet or capsule composition in general.
A sustained-release colchicine formulation.
Voriconazole, fluconazole, or cimetidine as compositions.
Every CYP3A4 inhibitor.
Every P-gp-negative CYP3A4 inhibitor.
Colchicine treatment for all inflammatory diseases.
A reduced-dose colchicine regimen during CYP3A4 inhibition.
A regimen involving a CYP3A4 inhibitor not named in the claims.
A regimen that fails to meet the stated treatment order.

This claim architecture makes the patent a method-of-use asset rather than a broad product patent.

When does U.S. Patent 8,927,607 lose exclusivity?

The patent was issued on December 30, 2014. Its ordinary U.S. patent term is generally measured from the earliest effective nonprovisional filing date, subject to patent-term adjustment and any applicable patent-term extension. The expected term is in the late 2020s, generally understood to be around 2028 based on the patent family timeline. The enforceable expiration date must be taken from the USPTO Patent Center record, including any patent-term adjustment.

Event	Date or status
Patent issued	December 30, 2014
Patent number	U.S. 8,927,607
Patent type	Method of treatment
Expected ordinary term	Late 2020s, approximately 2028
Patent-term adjustment	Must be confirmed in USPTO records
Patent-term extension	No extension is established from the claim text alone
Pediatric exclusivity	Does not arise from the patent itself

A patent expiration date does not automatically eliminate all colchicine exclusivity. Separate patents, regulatory exclusivities, labeling provisions, and other members of the family must be evaluated independently.

What is the Orange Book status of U.S. Patent 8,927,607?

Orange Book listing is product-specific. A patent is not listed merely because it relates to a drug or because it contains method-of-treatment claims. The NDA holder must submit an eligible patent for listing against the relevant approved product.

The commercial product most closely associated with this patent landscape is Colcrys, colchicine tablets, approved under NDA 022352. FDA regulations permit listing of patents claiming the drug substance, drug product, or an approved method of use, subject to the statutory and regulatory requirements. FDA, Approved Drug Products with Therapeutic Equivalence Evaluations.

The practical Orange Book questions are:

Whether U.S. 8,927,607 was submitted for listing against NDA 022352.
Whether FDA accepted the listing.
Which approved method of use corresponds to the patent.
Whether the listing remained active when generic colchicine ANDAs were filed.
Whether a generic applicant certified under Paragraph IV.

The patent number should not be treated as an Orange Book-listed patent without confirmation in the current FDA Orange Book data files. Orange Book status can change independently of the patent's underlying validity or enforceability.

What Paragraph IV challenges could target this patent?

A generic applicant seeking approval for colchicine may address an Orange Book-listed method patent through one of four principal certifications:

Paragraph I: no patent information is listed.
Paragraph II: the patent has expired.
Paragraph III: approval is sought after patent expiration.
Paragraph IV: the patent is invalid, unenforceable, or will not be infringed.

For this patent, a Paragraph IV challenge would likely focus on the following issues:

Anticipation and obviousness

The challenger could rely on prior art describing:

Colchicine toxicity caused by CYP3A4 inhibition.
Colchicine transport through P-gp.
Dose reduction or contraindication guidance for interacting drugs.
Voriconazole, fluconazole, or cimetidine pharmacology.
Clinical treatment of gout with fixed colchicine maintenance doses.

The strongest obviousness argument would combine known colchicine exposure concerns with known CYP3A4 inhibition and a clinical decision to maintain or adjust colchicine dosing. The patent owner would likely argue that the specific sequence, named inhibitors, disease indications, dose ranges, and unchanged-dose instruction were not taught in combination.

Written description and enablement

The claims cover three diseases, three inhibitors, multiple dose ranges, two treatment sequences, and an exclusion based on P-gp inhibition. A challenger could argue that the specification does not adequately support the full breadth of the claimed genus, particularly if the experimental disclosure is concentrated on only one inhibitor or one clinical scenario.

Enablement risk would depend on whether the specification provides a reliable basis for practicing every claimed combination without undue experimentation.

Indefiniteness

Potentially disputed phrases include:

“Therapeutically effective.”
“Fixed maintenance dose.”
“A plurality of days.”
“One or more therapeutically effective doses.”
“Without dose reduction.”
“Not an inhibitor of P-gp.”

The phrase “plurality of days” is narrowed to at least seven days in claim 8 but remains less precise in claim 1. The “not an inhibitor” limitation may also raise measurement questions because inhibitory activity depends on assay conditions, concentration, and the definition of clinically meaningful inhibition.

How strong is the patent estate for colchicine?

U.S. Patent 8,927,607 is narrower and more conduct-dependent than the primary product and formulation patents historically associated with colchicine products.

Patent category	Typical protection	Relative commercial strength
Compound patent	Colchicine molecule	Generally unavailable for an old active ingredient
Product patent	Colchicine tablet or dosage form	Moderate if narrowly drafted
Formulation patent	Excipients, release profile, stability	Moderate to strong depending on claim breadth
Dose patent	Specific colchicine dose or regimen	Moderate
Drug-interaction method patent	Colchicine with named CYP3A4 inhibitors	Narrow but potentially enforceable
Manufacturing patent	Purification, crystallization, or process	Relevant to API suppliers
Regulatory exclusivity	FDA approval or labeling protection	Separate from patent term

The '607 patent's strength is highest where a product label or clinical protocol expressly recommends continuing 0.6 mg/day or 1.2 mg/day colchicine during treatment with one of the named inhibitors for chronic gout, familial Mediterranean fever, or Behçet's disease.

Its strength is lower where:

The inhibitor is not one of the three claimed drugs.
The patient has a different indication.
The physician reduces or stops colchicine.
The treatment sequence does not match the claim.
The generic label omits the patented method under a section viii carve-out.
The relevant drug interaction is described only as a warning or contraindication.

What formulation patents and method-of-use patents compete with this patent?

The surrounding colchicine landscape generally divides into four areas.

Colchicine dose and administration patents

These patents address acute gout flares, prophylaxis, chronic gout, dosing frequency, and dose reduction. They can create separate infringement risks even if the '607 interaction claims are avoided.

Formulation patents

Formulation claims may cover:

Immediate-release tablets.
Modified-release dosage forms.
Particle-size distributions.
Stabilized colchicine compositions.
Combination products.
Manufacturing controls that affect content uniformity.

A generic applicant may avoid a formulation patent by using different excipients or manufacturing conditions while still confronting method-of-use patents.

Interaction and safety patents

The '607 patent belongs to this category. It focuses on the relationship among colchicine metabolism, CYP3A4 inhibition, P-gp activity, and treatment sequencing.

Manufacturing and API patents

Colchicine is an established natural product, so commercial barriers may arise from purification, impurity control, crystallization, scale-up, and analytical specifications rather than from the active molecule itself. These barriers affect suppliers and contract manufacturers even when a finished-dose generic avoids the '607 claims.

What litigation and settlement risks affect generic launch?

A Paragraph IV notice concerning an Orange Book-listed patent can trigger a 45-day period for the NDA holder to file an infringement action. A timely action can create a statutory 30-month stay of ANDA approval under the Hatch-Waxman framework, subject to statutory exceptions and court orders. 21 U.S.C. § 355(j)(5)(B)(iii).

For this patent, litigation would likely center on:

Whether the patent is properly listed.
Whether the proposed generic label induces the claimed use.
Whether a section viii labeling carve-out removes the patented method.
Whether the patent's “not a P-gp inhibitor” limitation is met.
Whether the claims are invalid over interaction and dosing prior art.
Whether physicians and patients perform every required step.

A settlement could involve a licensed date, a label amendment, a no-challenge provision, or a restriction on marketing for a particular indication. No settlement term should be inferred from the patent number alone.

Which companies are relevant to the competitive landscape?

The relevant commercial participants include:

Takeda Pharmaceuticals, associated with Colcrys commercialization and the branded colchicine market.
Generic colchicine sponsors that filed ANDAs for 0.6 mg tablets.
Manufacturers of voriconazole, fluconazole, and cimetidine.
API suppliers and contract manufacturers.
Specialty pharmaceutical companies selling gout and anti-inflammatory products.

The key competitive issue is not whether generic colchicine can be manufactured. It is whether a generic sponsor can obtain approval and market its product without inducing the claimed interaction-related use.

What generic launch scenarios exist?

Launch scenario	Patent risk
Full label includes unchanged colchicine dosing with named inhibitors	High method-of-use risk
Section viii carve-out removes the patented interaction use	Lower inducement risk, subject to FDA acceptance
Label instructs dose reduction or discontinuation	Lower literal infringement risk
Generic launches after patent expiration	No prospective infringement from the expired patent
Generic uses a different indication only	Reduced risk if the patented diseases are omitted
Generic label names fluconazole or voriconazole only as contraindicated	Depends on actual wording and physician conduct
Generic colchicine is approved for acute flares without chronic maintenance use	Lower risk under claims 1-17

A carve-out is not automatically complete protection. Courts examine the full labeling, marketing materials, communications, and foreseeable use. Conversely, a label that merely acknowledges an interaction does not necessarily induce the precise unchanged-dose regimen claimed by the patent.

Key Takeaways

U.S. Patent 8,927,607 is a narrow method-of-treatment patent covering colchicine used with voriconazole, fluconazole, or cimetidine.
The claims are limited to chronic gout, familial Mediterranean fever, and Behçet's disease.
Claims 1-12 cover inhibitor introduction after established colchicine therapy.
Claims 13-17 cover inhibitor-first treatment followed by colchicine and continued colchicine after inhibitor discontinuation.
The core limitation is continuation of a fixed 0.6-1.2 mg/day colchicine dose without reduction or adjustment.
The patent does not cover colchicine itself, generic colchicine products broadly, or all CYP3A4 inhibitors.
The expected patent term runs into the late 2020s, approximately 2028, subject to USPTO patent-term adjustment.
Orange Book listing must be confirmed against the current FDA listing for the relevant NDA.
Paragraph IV exposure depends heavily on whether a generic label induces the specific claimed use.
The principal validity issues are obviousness, written description, enablement, and indefiniteness.
Generic launch risk is highest for a full label that expressly permits unchanged colchicine dosing during voriconazole, fluconazole, or cimetidine therapy.

FAQs About U.S. Patent 8,927,607

Does U.S. Patent 8,927,607 cover all colchicine interactions?

No. It covers only the claimed combinations involving voriconazole, fluconazole, or cimetidine, together with the specified diseases, dosing, sequencing, and unchanged-dose requirements.

Can a generic colchicine applicant avoid the patent with a section viii statement?

Potentially. A section viii carve-out may reduce infringement risk if the patented method is removed from the proposed labeling and promotional materials. The result depends on the final FDA-approved label and actual marketing conduct.

Does a reduced colchicine dose avoid claims 1 through 12?

A reduced dose may avoid the express “without dose reduction” limitation in those claims. The complete regimen and other patents must still be evaluated.

Are voriconazole and fluconazole themselves blocked by this patent?

No. The patent claims methods of administering colchicine with those drugs. It does not claim the voriconazole or fluconazole products as compositions.

Does expiration of U.S. Patent 8,927,607 eliminate all generic colchicine barriers?

No. Other patents, Orange Book listings, regulatory requirements, formulation patents, manufacturing rights, and separate method-of-use claims may remain relevant.

References

U.S. Patent No. 8,927,607. (2014). Methods of treating inflammatory disorders with colchicine and CYP3A4 inhibitors. United States Patent and Trademark Office. https://patents.google.com/patent/US8927607
U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations: Orange Book. https://www.accessdata.fda.gov/scripts/cder/ob/
U.S. Food and Drug Administration. (n.d.). Colcrys (colchicine) prescribing information. https://www.accessdata.fda.gov/drugsatfda_docs/label/
U.S. Food and Drug Administration. (2009). FDA approves Colcrys for treatment and prevention of gout flares. https://www.fda.gov/
United States Code. (2024). 21 U.S.C. § 355(j): Abbreviated application for new drug. https://uscode.house.gov/
United States Patent and Trademark Office. (2024). Manual of Patent Examining Procedure, Chapter 2700: Patent terms and adjustments. https://www.uspto.gov/web/offices/pac/mpep/mpep-2700.html

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	8,927,607	⤷ 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: 8,927,607

Which drugs does patent 8,927,607 protect, and when does it expire?

Summary for Patent: 8,927,607