Details for Patent: 8,093,298

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Which drugs does patent 8,093,298 protect, and when does it expire?

Patent 8,093,298 protects COLCRYS and is included in one NDA.

Summary for Patent: 8,093,298

Title:	Methods for concomitant administration of colchicine and macrolide antibiotics
Abstract:	Methods for concomitant administration of colchicine together with one or more macrolide antibiotics, e.g., clarithromycin, are disclosed. Such methods reduce the dangers commonly associated with such concomitant administration and provide additional benefits.
Inventor(s):	Matthew W. Davis
Assignee:	Mutual Pharmaceutical Co Inc
Application Number:	US13/110,087
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,093,298
Patent Claim Types: see list of patent claims	Use; Dosage form;

United States Patent 8,093,298: Colchicine, Clarithromycin, and Familial Mediterranean Fever Patent Analysis

US Patent 8,093,298 protects a narrow dosing method for colchicine in patients with Familial Mediterranean Fever (FMF) who are receiving clarithromycin. The claims apply to three pediatric and adult age groups, require oral colchicine, require concomitant clarithromycin administration within a defined one-to-two-day window, and cap the adjusted colchicine dose at 0.6 mg per day.

The patent does not broadly cover colchicine, clarithromycin, FMF treatment, or colchicine products. Its commercial value depends on whether a competing product or prescribing information induces use of the specific claimed dose-adjustment regimen.

What does US Patent 8,093,298 cover?

The patent covers methods of reducing colchicine exposure when clarithromycin is administered to an FMF patient. Clarithromycin is a strong CYP3A4 and P-glycoprotein interaction risk for colchicine. Inhibition of these pathways can increase colchicine concentrations and toxicity risk.

The three claims are substantially parallel:

Claim	Patient population	Baseline maximum without clarithromycin	Adjusted maximum with clarithromycin
1	Adults and children older than 12 years	2.4 mg/day	0.6 mg/day
2	Children older than 6 through 12 years	1.8 mg/day	0.6 mg/day
3	Children aged 4 through 6 years	1.8 mg/day	0.6 mg/day

Each claim requires all of the following:

1. The patient has FMF and needs treatment.
2. The patient is an adult or falls within the specified pediatric age range.
3. Colchicine is administered orally.
4. The patient is concomitantly receiving clarithromycin.
5. Clarithromycin is administered within one to two days of the colchicine administration.
6. The colchicine dose is reduced compared with the dose used without clarithromycin.
7. The ordinary daily maximum is the amount stated in the applicable claim.
8. The reduced colchicine dose does not exceed 0.6 mg per day.

The claims are method-of-use claims, not composition claims. They do not require a particular colchicine tablet formulation, excipient system, particle size, salt, polymorph, or manufacturing process.

How narrow are the claims of US 8,093,298?

The claims are narrow because infringement requires simultaneous satisfaction of the disease, age, drug-interaction, timing, route, and dose limitations.

Disease limitation

The claims are limited to FMF. Use of colchicine for gout, pericarditis, Behcet's disease, amyloidosis prevention, or another inflammatory condition falls outside the literal claim language unless the use also satisfies the FMF limitation.

Age limitations

The patent divides patients into three groups:

• Adults and children older than 12 years.
• Children older than 6 years through 12 years.
• Children aged 4 through 6 years.

The age language creates boundary questions. A patient who is exactly 12 years old may fall within claim 2 rather than claim 1. A child exactly 6 years old is expressly addressed by claim 3, while a child older than 6 years is addressed by claim 2. The relevant age is likely assessed at the time of treatment, although litigation would examine the patent specification, prosecution history, and ordinary clinical meaning.

Clarithromycin limitation

The claims require clarithromycin, rather than merely any CYP3A4 inhibitor. A regimen involving erythromycin, azithromycin, ketoconazole, ritonavir, cyclosporine, or another interacting drug is not literally within these claims solely because it creates a similar pharmacokinetic concern.

Timing limitation

The claims require clarithromycin administration within one to two days of oral colchicine administration. This limitation is central. A patient who receives clarithromycin weeks before or after colchicine would not satisfy the literal timing requirement.

The phrase "within 1 to 2 days" can generate claim-construction issues because it may be read as a one-to-two-day interval surrounding the colchicine administration or as administration within a specified temporal period. Clinical records, prescription instructions, and actual administration dates would be important in an infringement dispute.

Dose limitation

The reduced colchicine amount must be no more than 0.6 mg per day. A dose of 0.6 mg is included. A dose above 0.6 mg per day is outside the express upper limit, even if it is lower than the ordinary maximum.

The claims also require a reduction from the dose that would be administered absent clarithromycin. A patient already receiving 0.6 mg per day without clarithromycin presents a potential issue because the claim requires a reduced amount, not simply a dose that is at or below 0.6 mg.

What patent protects colchicine dosing with clarithromycin in FMF?

US 8,093,298 is the principal patent directed to this specific FMF and clarithromycin dose-adjustment method. Its technical focus is the clinical management of a colchicine-drug interaction.

The patent estate around Colcrys and colchicine has included other method-of-use patents directed to colchicine dosing and treatment of gout or FMF. Those patents should be separated from US 8,093,298 because they may have different patient populations, dose ranges, interaction limitations, and expiration dates.

Protection category	Relevance to US 8,093,298
Colchicine active ingredient	Not claimed
Clarithromycin active ingredient	Not claimed
Colchicine tablet composition	Not claimed
FMF treatment generally	Not claimed broadly
Colchicine dose adjustment for clarithromycin	Claimed
Pediatric FMF dosing with clarithromycin	Claimed
Manufacturing process	Not claimed
Generic colchicine product as such	Not directly claimed
Prescribing or labeling that directs the claimed regimen	Potential infringement theory

The patent therefore has greater relevance to labeling and clinical-use analysis than to formulation or manufacturing freedom to operate.

What is the Orange Book status of US Patent 8,093,298?

US 8,093,298 has been associated with the Colcrys colchicine product and its FDA-approved FMF indication. Orange Book treatment depends on the patent listing maintained for the relevant NDA and the FDA's current patent database. FDA Orange Book listings identify patents submitted by NDA holders and do not independently determine infringement or patent validity (FDA, 2024a).

For an ANDA applicant, the key issue is whether the patent remains listed against the relevant Colcrys strength and indication at the time of filing. If listed, an applicant may need to submit one of the following certifications:

• Paragraph I: no patent information has been filed.
• Paragraph II: the patent has expired.
• Paragraph III: the applicant will wait until patent expiration.
• Paragraph IV: the patent is invalid, unenforceable, or will not be infringed.
• A section viii statement: the applicant will omit the patented method from its labeling, where legally available.

Because US 8,093,298 is a method-of-use patent, a section viii carve-out or a non-infringing label may be commercially important. The feasibility of a carve-out depends on whether the FMF indication and the clarithromycin dose-adjustment instructions can be removed without leaving the generic label with language that still encourages the patented use.

When does US Patent 8,093,298 lose exclusivity?

The patent was issued on January 10, 2012. Its term is governed by the patent term provisions applicable to the underlying application, including any patent-term adjustment and terminal disclaimer. Public patent records associate the Colcrys-related patent estate with an expiration period in the late 2020s, including June 2029 for relevant listed protection. The controlling date is the expiration date recorded by the USPTO and FDA Orange Book for the specific patent listing, rather than the grant date alone (USPTO, 2024; FDA, 2024a).

FDA regulatory exclusivity is separate from patent protection. Colcrys received approval in 2009 under NDA 022352. FDA's three-year exclusivity for a new clinical investigation does not extend patent term and expired substantially earlier than the patent estate. Any pediatric exclusivity associated with colchicine products also does not recreate or extend the patent's enforceable term after its statutory expiration.

Practical exclusivity timeline

Event	Date or period
Colcrys FDA approval	July 30, 2009
US 8,093,298 grant	January 10, 2012
FDA small-molecule exclusivity	Expired before current patent-term period
Patent protection	Late 2020s, subject to the controlling USPTO and Orange Book term
Generic entry analysis	Depends on patent certifications, litigation, settlements, and label design

Which companies have challenged Colcrys and colchicine patents?

Generic colchicine manufacturers have pursued FDA approval through the ANDA pathway. Commercial participants in the US colchicine market have included manufacturers and marketers such as Hikma, Amneal, Rising Pharmaceuticals, Actavis or Watson, and other ANDA sponsors.

A Paragraph IV challenge to a listed method-of-use patent can trigger Hatch-Waxman litigation under 35 U.S.C. § 271(e)(2). The filing of an ANDA is treated as a technical act of infringement for purposes of resolving patent rights before commercial launch. A listed patent challenge does not itself establish that the patent is valid, enforceable, or infringed.

The relevant litigation questions for US 8,093,298 are:

1. Was the patent listed against the reference product at the time of the ANDA filing?
2. Did the ANDA applicant submit a Paragraph IV certification?
3. Did the patent owner sue within 45 days?
4. Did the case involve this patent specifically or a broader Colcrys patent group?
5. Was the dispute resolved through a judgment, dismissal, license, or launch-date settlement?
6. Did the approved generic label retain or omit the FMF interaction regimen?

Patent litigation involving colchicine products frequently includes multiple patents. A settlement covering other Colcrys patents does not necessarily resolve the rights under US 8,093,298 unless the patent is expressly included.

What generic entry risks exist for US 8,093,298?

The patent presents a moderate enforcement risk for a generic whose label includes:

• FMF as an indication.
• Pediatric FMF treatment.
• Clarithromycin interaction instructions.
• A colchicine reduction to 0.6 mg per day.
• The specific age-group dosing structure recited in the claims.

The risk is lower where a generic applicant can omit the patented FMF use or interaction regimen through a permissible labeling carve-out. The risk increases if the reference-product labeling treats the claimed information as medically necessary for safe use or if the generic's label reproduces the same directions.

Direct infringement and induced infringement

Direct infringement would generally require an actual treatment regimen satisfying every claim element. A prescribing physician or treating institution could be the direct actor in a method claim.

A manufacturer may face induced-infringement allegations if its label, promotional materials, prescribing information, or distribution strategy encourages the claimed use. Courts evaluate the totality of the evidence, including whether the label provides instructions that naturally lead to the patented method.

A bare sale of colchicine is less likely to establish infringement of these claims because the patent does not claim the product itself. The interaction between product labeling and physician conduct is the central commercial issue.

How strong is the patent estate for US 8,093,298?

Strengths

• The claims identify a clinically specific drug interaction.
• The 0.6 mg/day ceiling is objective.
• The claims cover adults and pediatric patients from age 4 upward.
• The claims are tied to a recognized pharmacokinetic safety concern.
• An FMF label containing the claimed instructions could create meaningful induced-infringement exposure.

Weaknesses

• The claims are narrow and require multiple concurrent facts.
• They do not cover colchicine products, tablets, formulations, or manufacturing.
• They do not cover clarithromycin use outside FMF.
• They do not cover every CYP3A4 or P-glycoprotein inhibitor.
• The timing language may be subject to claim-construction disputes.
• A generic may attempt to omit the patented use from its label.
• Clinical use may not consistently document the exact one-to-two-day timing window.

The patent's value is therefore strongest as an Orange Book-listed method-of-use barrier and weaker as a stand-alone barrier to generic colchicine manufacture.

What formulations and manufacturing activities are protected?

US 8,093,298 does not claim a formulation. It does not require:

• A 0.6 mg tablet.
• A particular dosage form.
• A specific excipient.
• Immediate release or modified release.
• A particular particle-size distribution.
• A manufacturing sequence.
• A purity threshold.
• A crystalline form.
• A salt or prodrug of colchicine.

A manufacturer may still encounter separate patents covering colchicine formulations, tablet manufacture, packaging, stability, or delivery systems. Those rights require a separate patent-family and claim-level review. They cannot be inferred from US 8,093,298.

Does US 8,093,298 create biosimilar risk?

No conventional biosimilar risk applies. Colchicine is a small-molecule drug, not a biologic regulated through the biosimilar pathway under the Public Health Service Act.

The relevant competitive pathway is an ANDA for a generic colchicine product. The principal regulatory issues are bioequivalence, labeling, indication carve-outs, patent certifications, and any litigation stay under Hatch-Waxman.

How does this patent compare with formulation and general-use patents?

Patent type	Primary barrier	Relevance to generic colchicine
US 8,093,298	FMF dosing with clarithromycin	Label and method-of-use risk
General FMF method patent	Colchicine treatment of FMF	Broader indication risk
Gout dosing patent	Colchicine dosing for acute or chronic gout	Separate indication risk
Formulation patent	Tablet composition or delivery	Product-development risk
Manufacturing patent	Process or purification	Supply-chain and CMC risk
Orange Book method patent	Approved-use instructions	ANDA certification and label risk

US 8,093,298 should not be treated as a blocking patent for every generic colchicine product. Its blocking effect depends on the generic's approved indications and labeling.

Key Takeaways

• US 8,093,298 claims a method for reducing oral colchicine to no more than 0.6 mg/day in FMF patients receiving clarithromycin.
• The claims cover adults and children older than 12, children older than 6 through 12, and children aged 4 through 6.
• Every claim requires FMF, oral colchicine, clarithromycin, the specified timing relationship, and a reduced dose.
• The patent does not claim colchicine itself, clarithromycin, a tablet formulation, or a manufacturing process.
• The main generic-entry issue is whether an ANDA applicant can omit or redesign the FMF and clarithromycin interaction instructions.
• Paragraph IV litigation, section viii carve-outs, and settlement terms must be assessed across the entire Colcrys patent group.
• No biosimilar pathway applies because colchicine is a small-molecule drug.
• Patent protection associated with this Colcrys method-of-use estate extends into the late 2020s, with the controlling expiration date determined from the current USPTO and Orange Book records.

Frequently Asked Questions

Can a generic colchicine manufacturer sell a product without practicing US 8,093,298?

Yes. The patent claims a method of use, not the colchicine product. A generic manufacturer may reduce risk through a non-infringing label, an approved indication carve-out, or a successful patent challenge.

Does a 0.6 mg colchicine tablet automatically infringe this patent?

No. Tablet strength alone is insufficient. The claimed FMF indication, clarithromycin coadministration, timing, patient age, dose reduction, and daily maximum must also be present.

Does the patent cover clarithromycin use in gout patients?

No. The claims are limited to treatment of FMF. Clarithromycin-associated colchicine dosing for gout is outside the literal scope of these claims.

Can a physician infringe US 8,093,298 by prescribing colchicine and clarithromycin?

Potentially, if the prescribed regimen satisfies every claim limitation. The key facts would include the patient's FMF diagnosis, age, oral administration, timing, baseline dose, and reduced dose.

Is US 8,093,298 a formulation patent for Colcrys?

No. It is a method-of-use patent directed to dose reduction during concomitant clarithromycin administration in FMF patients.

References

1. Food and Drug Administration. (2024a). Approved drug products with therapeutic equivalence evaluations: Orange Book. U.S. Department of Health and Human Services. https://www.accessdata.fda.gov/scripts/cder/ob/

2. Food and Drug Administration. (2024b). Colcrys prescribing information. U.S. Department of Health and Human Services.

3. United States Patent and Trademark Office. (2024). Patent Center and Patent Examination Data System records for U.S. Patent No. 8,093,298. https://patentcenter.uspto.gov/

4. U.S. Patent No. 8,093,298, Methods of treating familial Mediterranean fever (issued Jan. 10, 2012).

5. Drug Price Competition and Patent Term Restoration Act of 1984, 21 U.S.C. § 355(j).

Drugs Protected by US Patent 8,093,298

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Takeda Pharms Usa	COLCRYS	colchicine	TABLET;ORAL	022352-001	Jul 29, 2009		DISCN	Yes	No	8,093,298					METHOD OF ADMINISTERING COLCHICINE TO FAMILIAL MEDITERRANEAN FEVER PATIENTS