US Patent 10,265,281: Scope, Validity, Orange Book Position and Colchicine Cardiovascular Patent Landscape

US Patent 10,265,281 protects once-daily administration of low-dose colchicine, generally 0.5 mg and no more than approximately 0.6 mg, for reducing cardiovascular risk. Its strongest commercial application is the FDA-approved LoDoCo formulation marketed as LODOCO by Agepha Pharma. The patent is a method-of-use patent, not a broad composition-of-matter patent. Its practical value depends on whether a competing product label, promotional activity, or physician-use evidence supports the claimed cardiovascular indication.

The patent’s reported priority date is May 4, 2015, producing an expected expiration date of May 4, 2036, subject to patent-term adjustment, patent-term extension, terminal disclaimers, and any post-grant changes recorded by the USPTO.

What does US Patent 10,265,281 protect?

US 10,265,281 protects a treatment method with four principal elements:

A subject in need of cardiovascular treatment or risk reduction.
A composition containing no more than approximately 0.6 total mg of colchicine or a colchicine salt.
Once-daily administration.
Treatment or reduction of the risk of a cardiovascular event.

The independent claims are claims 1 and 19.

Claim	Core limitation	Commercial significance
1	Once-daily administration of no more than approximately 0.6 mg colchicine for cardiovascular treatment or risk reduction	Broadest independent claim
19	Once-daily, homogeneous tablet containing no more than approximately 0.6 mg colchicine for specified cardiovascular events	Narrower product-aligned claim
4	Approximately 0.5 mg colchicine	Tracks LODOCO’s labeled strength
5-7	Atherosclerotic vascular disease, including clinically stable coronary disease	Tracks chronic secondary-prevention use
8	Acute coronary syndrome, out-of-hospital cardiac arrest, or noncardioembolic ischemic stroke	Defines particular cardiovascular outcomes
9-11	Co-administration with a colchicine-compatible statin	Addresses common cardiovascular treatment combinations
13-16	Specified reductions in cardiovascular-event risk	Adds outcome-based limitations
17-18	Reduced gastrointestinal risk compared with higher-dose colchicine	Supports low-dose tolerability theory

How broad is the scope of claim 1?

Claim 1 is broad in route, dosage form, and treatment context, but narrow in dose and frequency.

The claim covers:

Colchicine itself.
A colchicine salt.
A combination of colchicine and a colchicine salt.
Any route listed in dependent claim 2, including oral, parenteral, topical, ophthalmic, intranasal, inhaled, buccal, rectal, vaginal, intracranial, intraventricular, and implanted-reservoir administration.
Tablets, capsules, liquids, gels, and powders under claim 3.
Doses of approximately 0.5 mg under claim 4.
Subjects with atherosclerotic vascular disease or coronary disease.
Clinically stable coronary disease.
Several specified cardiovascular events.
Co-administration with statins.

The central limitation is the combination of low dose and daily dosing. A product administered twice daily, or a regimen using more than approximately 0.6 total mg per day, would present a stronger non-infringement position if the dosing schedule is reflected in the approved label and actual use.

The claim does not require a specific brand, tablet excipient, manufacturing process, crystal form, polymorph, release profile, or capsule shell.

What does claim 19 add?

Claim 19 is narrower and more directly aligned with a commercial low-dose colchicine tablet. It requires that:

The composition is administered once per day.
The composition is a tablet.
The tablet is homogeneous.
The tablet contains no more than approximately 0.6 total mg colchicine.
The cardiovascular event is acute coronary syndrome, out-of-hospital cardiac arrest, or noncardioembolic ischemic stroke.

Claim 19 does not expressly require atherosclerotic vascular disease or stable coronary disease, although those limitations appear in dependent claims 21-23.

The “homogeneous” limitation may have practical importance. A generic tablet containing a uniform colchicine distribution could satisfy the limitation if the term is construed according to its ordinary pharmaceutical meaning. The limitation may not require a particular blend uniformity specification unless the patent specification or prosecution history narrows the term.

What are the key claim-construction issues?

What does “no more than about 0.6 total mg” mean?

The phrase creates two issues:

“No more than” sets an upper boundary.
“About” introduces a range around 0.6 mg.

The claim is strongest against a clearly labeled 0.5 mg once-daily product. It is less certain at doses near or above 0.6 mg because the acceptable scope of “about” depends on the specification, examples, prosecution history, and expert evidence.

“Total mg” also prevents a defendant from avoiding the limitation by distributing colchicine across multiple forms or components in the same administered composition.

What does “once per day” mean?

The claim requires a once-daily regimen. A product label recommending one tablet daily is likely to satisfy this limitation. A product labeled for flexible or divided dosing may create a non-infringement argument, but actual prescribing instructions and promotional conduct could affect the analysis.

What is a “cardiovascular event”?

Claim 1 uses a broad cardiovascular-event concept. Claim 8 narrows the field to acute coronary syndrome, out-of-hospital cardiac arrest, and noncardioembolic ischemic stroke. Claim 19 incorporates the same event group.

The term is likely to be read in view of the specification and clinical evidence. A general anti-inflammatory use of colchicine for gout or familial Mediterranean fever does not inherently practice the cardiovascular-event limitation.

What is a “therapeutically effective amount”?

This is a functional limitation. The dose must be administered in an amount effective to treat or reduce cardiovascular risk. A 0.5 mg tablet supplied for an unrelated indication would not automatically meet this element.

Which claims are most relevant to LODOCO?

LODOCO’s labeled 0.5 mg once-daily oral tablet is closely aligned with claims 1, 3, 4, 5, 6, 7, 12, 19, 20, 21, 22, and 23.

LODOCO label characteristic	Corresponding patent limitation
Colchicine 0.5 mg	Claims 4 and 20
Oral tablet	Claims 2, 3, and 19
Once-daily dosing	Claims 1 and 19
Cardiovascular risk reduction	Claims 1 and 19
Atherosclerotic cardiovascular disease	Claims 5, 21
Stable coronary disease	Claims 7 and 23
Homogeneous tablet	Claim 19
Combination with standard cardiovascular therapy	Claims 9-11

The FDA approved LODOCO in June 2023 to reduce the risk of myocardial infarction, stroke, coronary revascularization, and cardiovascular death in adults with atherosclerotic disease or multiple risk factors for cardiovascular disease. The label uses 0.5 mg orally once daily, which is within the core claim architecture. [1]

What is the Orange Book status of US 10,265,281?

US 10,265,281 has been associated with the LODOCO regulatory and commercial patent position. The relevant FDA listing question is whether the patent is currently listed against LODOCO’s NDA and whether the listing identifies a method-of-use code covering the approved cardiovascular indication.

Because this is a method-of-use patent, the listing would ordinarily protect an approved use rather than the physical colchicine molecule. A generic applicant may be able to omit the patented indication through a section viii statement if the proposed label excludes the protected use. If the generic label includes the cardiovascular indication, a Paragraph IV certification and patent litigation risk become more likely.

The Orange Book should be evaluated together with the NDA patent-use code, any patent delisting, and any later-listed continuation patents. The patent itself does not prevent all sales of colchicine. It principally creates risk for an FDA-approved or promoted low-dose cardiovascular indication.

When does US Patent 10,265,281 lose exclusivity?

The expected base expiration date is May 4, 2036, based on the reported May 4, 2015 priority date and a standard 20-year patent term measured from the earliest nonprovisional or PCT filing that establishes the term.

Milestone	Date or status
Earliest reported priority	May 4, 2015
Patent grant	March 5, 2019
Expected base expiration	May 4, 2036
FDA LODOCO approval	2023
Likely commercial relevance	Through the mid-2030s, subject to later patents and challenges

The legally operative expiration date should be taken from the USPTO Patent Center record, including any patent-term adjustment. FDA regulatory exclusivity is separate from patent exclusivity. LODOCO’s New Chemical Entity exclusivity would not be expected to apply because colchicine was previously approved.

Are there Paragraph IV challenges to the patent?

A Paragraph IV challenge would be relevant if an abbreviated new drug application applicant seeks approval for a colchicine product with the patented cardiovascular indication or otherwise makes a label that encourages the claimed use.

The main pathways are:

Section viii carve-out

A generic applicant may omit the patented cardiovascular indication and retain only non-patented uses, such as gout flares or familial Mediterranean fever. This approach reduces direct label-based inducement risk but does not eliminate risk arising from physician prescribing, marketing, or other evidence of intent.

Paragraph IV certification

A generic applicant may certify that the patent is invalid, unenforceable, or not infringed. If the NDA holder or patent owner sues within the statutory period, FDA approval may be subject to a 30-month stay, subject to statutory exceptions and court developments. [2]

Litigation status

No litigation conclusion should be inferred merely from the existence of the patent or from generic colchicine approvals. A generic colchicine approval does not establish clearance for the patented cardiovascular use. The relevant litigation search must include district court filings, ANDA numbers, Paragraph IV notices, settlements, and Federal Circuit decisions.

What generic entry risks exist for low-dose colchicine?

Generic entry risk is asymmetric.

Product strategy	Patent risk
0.6 mg colchicine for gout only	Lower method-of-use risk
0.5 mg tablet with cardiovascular indication	High risk under claims 1 and 19
0.5 mg tablet with carved-out label	Moderate risk, depending on conduct
More than 0.6 mg daily	Lower risk under literal dose limitation
Divided-dose regimen	Lower risk under once-daily limitation
Non-tablet dosage form	Avoids claim 19 but may still implicate claim 1
Cardiovascular promotional campaign	Higher induced-infringement risk
Physician off-label use without sponsor conduct	More difficult inducement case

The most important commercial distinction is between product-level availability and indication-level clearance. Colchicine has long been available in the United States, but that does not mean a generic manufacturer is free to market a low-dose cardiovascular product.

How strong is the patent estate?

US 10,265,281 has a commercially meaningful but technically vulnerable estate.

Strengths

The 0.5 mg once-daily regimen maps closely to the approved product.
The claims cover the indication and dosing combination most likely to generate branded revenue.
Claim 1 is broad across routes and dosage forms.
Claim 19 provides a narrower tablet claim that may be easier to apply to a commercial product.
The claims include stable coronary disease and atherosclerotic vascular disease, which are clinically relevant populations.
The method-of-use structure may support enforcement against a labeled cardiovascular product even though colchicine itself is old.

Vulnerabilities

Colchicine is an old active ingredient with extensive prior art.
Low-dose colchicine treatment for cardiovascular inflammation may face obviousness attacks based on earlier clinical and mechanistic disclosures.
The 0.5 mg dose and once-daily schedule may be argued to be routine optimization.
Functional cardiovascular-risk limitations may raise enablement, written-description, or indefiniteness issues if the specification does not support the full claimed event spectrum.
Claims 13-16 depend on quantified risk reduction that may be difficult to prove for an individual patient or accused product.
Claims 17-18 require comparative gastrointestinal-risk evidence and may be less useful for routine infringement litigation.

Overall, the estate is stronger against a labeled LODOCO substitute than against an unlabeled colchicine product. The commercial patent position is likely medium to strong for indication-specific enforcement and weaker for blocking broad generic colchicine availability.

What manufacturing and formulation IP barriers exist?

The patent does not claim a specific manufacturing process or a unique colchicine crystal form. Its principal barrier is use, not manufacture.

A competing manufacturer could potentially avoid claim 19 by using:

A capsule rather than a tablet.
A non-homogeneous or modified formulation, subject to claim interpretation.
A dose above the claimed threshold.
A divided-dose regimen.
A label that excludes cardiovascular risk reduction.

Those changes would not necessarily avoid claim 1, which reaches multiple dosage forms and routes. The strongest design-around generally combines a non-infringing label with a regimen outside the dose or frequency limitations.

The use of a colchicine salt also does not automatically avoid the patent. Claims 1 and 19 expressly cover colchicine salts and combinations of colchicine and salts.

How does this patent compare with generic colchicine patents?

Issue	US 10,265,281	Conventional generic colchicine portfolio
Patent type	Cardiovascular method-of-use	Product, formulation, process, or use patents
Active ingredient	Colchicine or salt	Usually colchicine
Dose focus	No more than approximately 0.6 mg, commonly 0.5 mg	Often 0.6 mg or labeled product strength
Frequency	Once daily	May vary by indication
Cardiovascular indication	Central limitation	Usually absent from generic labels
Tablet homogeneity	Required by claim 19	Not generally central
Manufacturing process	Not claimed in the supplied claims	May be claimed elsewhere
Main enforcement theory	Direct or induced method infringement	Product or process infringement

The patent is therefore not a conventional barrier to all colchicine competition. It is a targeted barrier to low-dose cardiovascular risk-reduction commercialization.

What revenue exposure does the patent create?

The relevant revenue exposure is the branded cardiovascular colchicine market rather than the entire U.S. colchicine market.

Risk is highest for a competitor that:

Obtains approval for a cardiovascular risk-reduction indication.
Uses a 0.5 mg once-daily tablet.
Promotes use in atherosclerotic cardiovascular disease.
Markets the product as a substitute for LODOCO.
Relies on clinical materials describing reductions in myocardial infarction, stroke, or cardiovascular death.

Risk is lower for products limited to gout and familial Mediterranean fever. The economic value of the patent depends on LODOCO prescription volume, price relative to generic colchicine, payer coverage, and the ability of generic companies to carve out the patented cardiovascular indication.

Key Takeaways

US 10,265,281 is a low-dose colchicine cardiovascular method-of-use patent.
The commercial core is 0.5 mg once-daily administration.
Claim 1 is broad across dosage forms and routes but requires no more than approximately 0.6 mg and once-daily dosing.
Claim 19 is narrower and targets a homogeneous once-daily tablet for specified cardiovascular events.
The expected base expiration date is May 4, 2036.
The patent does not block all colchicine products or all generic colchicine sales.
The main risk is for a generic or follow-on product carrying the cardiovascular indication.
A section viii carve-out may reduce label-based infringement risk.
A 0.5 mg once-daily cardiovascular product would face the highest infringement and Paragraph IV exposure.
The estate is commercially strong for indication-specific enforcement but vulnerable to prior-art, obviousness, claim-construction, and enablement challenges.

FAQs

Does US 10,265,281 cover colchicine for gout?

No. The supplied claims require treatment or reduction of the risk of a cardiovascular event. Colchicine use for gout or familial Mediterranean fever does not inherently satisfy that limitation.

Does a 0.6 mg colchicine tablet infringe the patent?

It may, if it is administered once daily for the claimed cardiovascular purpose and falls within the construction of “no more than about 0.6 total mg.” The result depends on the evidence concerning the meaning of “about.”

Can a generic company sell colchicine without infringing this patent?

Potentially. A generic company may reduce risk by excluding the cardiovascular indication, using a different regimen, or relying on a product and label that do not satisfy the method limitations. Actual marketing conduct remains relevant.

Does the patent cover rosuvastatin-colchicine combination therapy?

It can cover co-administration of colchicine with rosuvastatin under claims 9-11, provided the other limitations of claim 1 are met. The patent does not require the two agents to be in a single fixed-dose tablet.

Is US 10,265,281 a composition-of-matter patent?

No. The supplied claims are method claims. They cover administering colchicine or a colchicine salt for a specified cardiovascular purpose, rather than claiming colchicine as a new chemical entity.

References

U.S. Food and Drug Administration. (2023). LODOCO (colchicine) tablets, 0.5 mg: Prescribing information. FDA.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book. FDA.
United States Patent and Trademark Office. (2019). U.S. Patent No. 10,265,281, methods of treating cardiovascular disease with colchicine. USPTO.
U.S. Food and Drug Administration. (2017). ANDA approvals and patent certifications under the Hatch-Waxman Amendments. FDA.
Tardif, J.-C., Kouz, S., Waters, D. D., et al. (2019). Efficacy and safety of low-dose colchicine after myocardial infarction. New England Journal of Medicine, 381(26), 2497-2505.
Nidorf, S. M., Fiolet, A. T. L., Most cardiovascular investigators, et al. (2020). Colchicine in patients with chronic coronary disease. New England Journal of Medicine, 383(19), 1838-1847.

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Agepha Pharma Fz	LODOCO	colchicine	TABLET;ORAL	215727-001	Jun 16, 2023		RX	Yes	Yes	⤷ Start Trial	⤷ Start Trial				A METHOD FOR TREATING AND/OR REDUCING THE RISK OF A CARDIOVASCULAR EVENT	⤷ 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

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2013337605	⤷ Start Trial
Australia	2018203715	⤷ Start Trial
Australia	2019232879	⤷ Start Trial
Australia	2021282491	⤷ Start Trial
Australia	2024205084	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 10,265,281

Which drugs does patent 10,265,281 protect, and when does it expire?

Summary for Patent: 10,265,281