Details for Patent: 10,555,925

Which drugs does patent 10,555,925 protect, and when does it expire?

Patent 10,555,925 protects VASCEPA and is included in one NDA.

This patent has one hundred and thirteen patent family members in forty-one countries.

Summary for Patent: 10,555,925

Title:	Methods of reducing the risk of a cardiovascular event in a subject at risk for cardiovascular disease
Abstract:	In various embodiments, the present invention provides methods of reducing the risk of a cardiovascular event in a subject on statin therapy and, in particular, a method of reducing the risk of a cardiovascular event in a subject on statin therapy having a fasting baseline triglyceride level of about 135 mg/dL to about 500 mg/dL, and administering to the subject a pharmaceutical composition comprising about 1 g to about 4 g of eicosapentaenoic acid ethyl ester or a derivative thereof.
Inventor(s):	Paresh Soni
Assignee:	Amarin Pharmaceuticals Ireland Ltd
Application Number:	US16/599,412
Patent Claim Types: see list of patent claims	Use; Composition; Dosage form;

US Patent 10,555,925: Scope, Claims, Expiration, Litigation, and Vascepa Patent Landscape

US Patent 10,555,925 protects the use of approximately 4 g per day of icosapent ethyl to reduce stroke risk in patients with established cardiovascular disease. The patent is a method-of-use patent covering the REDUCE-IT treatment paradigm, with dependent claims directed to triglyceride and LDL-C ranges, purified omega-3 composition, four-capsule dosing, treatment of at least two years, and concomitant statin therapy.

The patent is commercially important because it covers the cardiovascular-risk-reduction indication for Vascepa, not merely treatment of severe hypertriglyceridemia. Generic manufacturers have been able to market icosapent ethyl under restricted or "skinny" labels that omit the protected cardiovascular indication, creating a continuing induced-infringement and labeling dispute.

What does US Patent 10,555,925 protect?

US 10,555,925 protects a therapeutic method rather than the icosapent ethyl molecule itself. The core elements are:

Element	Claim 1 requirement
Patient population	Subject with established cardiovascular disease
Active ingredient	Ethyl icosapentate, also called icosapent ethyl
Dose	About 4 g per day
Therapeutic objective	Reducing the risk of stroke
Treatment period	A period effective to reduce stroke risk

The claim does not expressly require:

• A particular baseline triglyceride level
• A particular LDL-C level
• Statin therapy
• A specified capsule formulation
• A specific treatment duration
• A particular age, sex, cardiovascular diagnosis, or prior stroke history

Those features appear in dependent claims or in the specification.

The claim is closely aligned with the REDUCE-IT clinical program, in which icosapent ethyl was administered at 4 g daily to statin-treated patients with elevated triglycerides and controlled LDL-C who had established cardiovascular disease or diabetes plus additional risk factors. REDUCE-IT reported a significant reduction in major adverse cardiovascular events, including nonfatal stroke, compared with placebo. [1]

How broad is claim 1 of US 10,555,925?

Claim 1 is the commercially important claim because it combines a broad patient population with a broad functional outcome.

A potential infringement analysis would generally require proof that:

1. The patient has established cardiovascular disease.
2. The product administered is ethyl icosapentate.
3. The daily dose is approximately 4 g.
4. The administration is for the purpose of reducing stroke risk.
5. The treatment is effective for that purpose.

The words "about 4 g" create a dosing range rather than a strict 4.000 g requirement. The scope would likely encompass the labeled 4 g daily dose delivered as four 1 g capsules. It may also cover clinically equivalent dosing regimens that use approximately 4 g per day, subject to claim construction and proof of infringement.

The phrase "for a period effective to reduce risk of stroke" is a functional limitation. It ties the method to the treatment objective but does not impose an express fixed duration in claim 1. Claim 5 narrows the method by requiring treatment to continue for at least two years.

The claim is narrower than a claim covering all use of icosapent ethyl in cardiovascular patients because it requires established cardiovascular disease and stroke-risk reduction. It is broader than a claim limited to the exact REDUCE-IT laboratory criteria because those criteria are not included in claim 1.

What limitations are added by claims 2 through 6?

Claim 2: triglyceride and LDL-C ranges

Claim 2 requires:

• Fasting baseline triglycerides of about 135 mg/dL to about 500 mg/dL
• Fasting baseline LDL-C of about 40 mg/dL to about 100 mg/dL

This limitation tracks the REDUCE-IT enrollment population more closely than claim 1. It narrows the patent to patients with moderate residual hypertriglyceridemia and controlled LDL-C.

The claim does not require that the patient remain within those ranges during treatment. The relevant values are baseline values, meaning measurements taken before or at the start of treatment. A generic label that expressly identifies those ranges could increase exposure under claim 2, although the label would still need to be assessed for the other elements of the claim.

Claim 3: high-purity omega-3 composition

Claim 3 requires that:

• Icosapent ethyl is present in a pharmaceutical composition; and
• Icosapent ethyl comprises at least approximately 96 weight percent of all omega-3 fatty acids in that composition.

This limitation separates purified icosapent ethyl from mixed omega-3 products such as prescription omega-3-acid ethyl esters containing EPA and DHA.

The claim is directed to the composition used in the method. It does not require a particular excipient, capsule shell, manufacturing process, particle size, or release profile.

Claim 4: four-capsule presentation

Claim 4 requires approximately 1 g of the pharmaceutical composition in each of four capsules. The practical embodiment is four 1 g capsules administered daily.

This claim is narrower than claim 3 because it requires both the high-purity composition and a particular dose presentation. A product using two 2 g dosage units could fall outside the literal wording of claim 4 while potentially remaining within broader method claims, depending on the actual amount of icosapent ethyl and the interpretation of "about."

Claim 5: at least two years of treatment

Claim 5 requires that the treatment period end at least two years after initial administration.

The limitation is significant for infringement analysis because a short-term prescription may not satisfy the literal claim. It is less significant for the commercial protection of the cardiovascular indication because the broader independent claim does not impose the two-year duration.

A treatment plan, label, or clinical protocol that recommends ongoing daily therapy could support an infringement theory even where individual patients discontinue before two years. The result would depend on the governing inducement and divided-infringement standards and on the content of the generic label.

Claim 6: statin therapy

Claim 6 requires that the subject be receiving statin therapy.

This limitation corresponds to the background standard of care in REDUCE-IT. It is narrower than claim 1 because claim 1 does not require statin use. A label that instructs physicians to prescribe icosapent ethyl only as an adjunct to statin therapy could implicate claim 6 as well as the broader claims.

What is the FDA and Orange Book status of US 10,555,925?

US 10,555,925 is associated with the Vascepa, or icosapent ethyl, cardiovascular-risk-reduction product. The relevant regulatory framework is an NDA for Vascepa and abbreviated new drug applications for generic icosapent ethyl.

The patent is a method-of-use patent. It does not provide composition-of-matter protection for icosapent ethyl. Its commercial value comes from the FDA-approved cardiovascular-risk-reduction indication and the ability to list the patent in the Orange Book against that indication.

Regulatory issue	Status and significance
Product	Vascepa, icosapent ethyl
FDA pathway	NDA for the branded product; ANDA pathway for generics
Patent type	Method of treatment and use
Orange Book relevance	Protects an approved use rather than the active ingredient itself
Generic pathway	Paragraph IV challenge or label carve-out under a section viii strategy
Biosimilar pathway	Not applicable; icosapent ethyl is a small molecule

FDA approval of Vascepa for cardiovascular-risk reduction followed the REDUCE-IT results and expanded the product beyond its earlier severe-hypertriglyceridemia indication. [2] FDA-approved labeling identifies 4 g daily as the cardiovascular-risk-reduction dose. [3]

When does US Patent 10,555,925 expire?

Public patent records identify the expected expiration of US 10,555,925 as approximately September 22, 2033, subject to the patent’s applicable term adjustment, terminal-disclaimer, and regulatory-term records. The patent issued on February 11, 2020. [4]

Milestone	Date
Earliest reported priority	October 21, 2011
Patent issued	February 11, 2020
Patent number	US 10,555,925 B2
Expected patent expiration	Approximately September 22, 2033

The patent term should be distinguished from FDA regulatory exclusivity. FDA exclusivity is a regulatory period attached to approval of a new indication or product. Patent expiration is controlled by the patent statute and the patent’s prosecution history. The commercial generic-entry date can therefore differ from either date because of Paragraph IV litigation, settlements, labeling carve-outs, and court orders.

Which patents are part of the Vascepa patent estate?

The Vascepa estate includes composition, formulation, treatment-method, and cardiovascular-risk-reduction patents. The most commercially relevant family members include the following:

Patent	General subject matter	Commercial relevance
US 8,617,659	Icosapent ethyl composition and related product protection	Earlier product protection
US 9,700,537	Cardiovascular-risk-reduction methods	REDUCE-IT-related use protection
US 10,555,925	Stroke-risk reduction using approximately 4 g/day	Specific method-of-use protection
US 10,568,861	Cardiovascular treatment methods	Overlapping REDUCE-IT use protection
US 10,583,155	Icosapent ethyl cardiovascular-use claims	Method-of-use and indication protection
US 10,603,266	Cardiovascular-risk-reduction methods	Orange Book and ANDA relevance
US 10,610,536	Use of icosapent ethyl in cardiovascular-risk patients	Overlapping use protection

The estate has greater breadth through overlapping method claims than through US 10,555,925 alone. Several patents address substantially similar clinical use concepts but differ in patient selection, lipid parameters, dosing, cardiovascular endpoints, or formulation requirements.

The estate does not provide the same type of barrier as a valid composition-of-matter patent covering the molecule. Once the active ingredient is known and the generic can rely on an approved noninfringing indication, the remaining risk is primarily method-of-use infringement.

What patent litigation affects Vascepa and icosapent ethyl?

Amarin brought Paragraph IV litigation against generic manufacturers, including Hikma Pharmaceuticals and Dr. Reddy’s Laboratories, over patents covering Vascepa and its cardiovascular-risk-reduction use. The central commercial issue was whether generic labels that omitted the cardiovascular indication could still induce infringement of the method patents.

In 2020, the Federal Circuit affirmed the invalidation of key Vascepa patents on obviousness grounds in litigation involving Amarin and generic challengers. The decision materially weakened Amarin’s ability to use the original REDUCE-IT patent set as a complete barrier to generic entry. [5]

The subsequent litigation environment shifted toward newer patents and induced-infringement theories. Generic manufacturers used labeling that focused on the severe-hypertriglyceridemia indication while omitting the cardiovascular-risk-reduction indication. Such a label strategy is commonly called a skinny label or section viii carve-out.

The principal legal questions are:

• Whether the generic label recommends or encourages the patented cardiovascular use.
• Whether promotional materials go beyond the carved-out indication.
• Whether the physician’s prescribing behavior is attributable to the generic manufacturer.
• Whether the asserted patent claims are valid and enforceable.
• Whether the patent claims cover the generic product’s exact dose and patient population.

A generic can still face litigation even when the cardiovascular indication is omitted from its FDA label. FDA labeling, product websites, prescribing information, distributor communications, and sales materials are all relevant to an induced-infringement analysis.

What Paragraph IV challenges and generic launch scenarios exist?

Generic icosapent ethyl manufacturers have used two principal strategies.

Paragraph IV certification

A Paragraph IV certification asserts that an Orange Book-listed patent is invalid, unenforceable, or not infringed. The ANDA applicant may seek approval before patent expiration. Filing the certification can trigger a patent-infringement action and a 30-month stay of FDA approval under the Hatch-Waxman Act, subject to statutory conditions. [6]

Section viii label carve-out

A section viii statement removes a patented indication from the generic label. The generic can then seek approval for an unprotected indication, such as severe hypertriglyceridemia, while excluding cardiovascular-risk reduction.

The principal launch scenarios are:

Scenario	Commercial result
Full-label approval after patent defeat	Generic may market both major indications
Skinny-label approval	Generic markets the nonprotected indication while omitting cardiovascular use
Settlement with delayed entry	Entry occurs on an agreed date, potentially before patent expiration
Injunction or successful induced-infringement case	Launch is delayed or restricted
Patent invalidity with no enforceable replacement	Broad generic substitution becomes possible

The severe-hypertriglyceridemia indication is less central to the remaining patent risk because it is distinct from the REDUCE-IT cardiovascular indication. The commercial exposure lies in whether physicians prescribe generic icosapent ethyl for cardiovascular-risk reduction despite the carved-out label.

How strong is the patent estate for icosapent ethyl?

The estate is moderate for the active ingredient and stronger for the specific cardiovascular-use indication, but it is less secure than a new-molecule estate.

Strengths

• The claims map to a large cardiovascular market.
• The 4 g daily dose is commercially standardized.
• The patient population is clinically identifiable.
• REDUCE-IT provides substantial clinical support for cardiovascular-risk-reduction claims.
• Multiple method patents create overlapping litigation positions.
• The FDA-approved indication gives the patent holder a clear regulatory and commercial use to protect.

Weaknesses

• Icosapent ethyl is an established omega-3 derivative rather than a new chemical entity.
• The claims are method claims and depend on patient treatment and prescribing behavior.
• Generic manufacturers can carve out the cardiovascular indication.
• Earlier Vascepa patents were invalidated in obviousness litigation.
• Claims tied to clinical outcomes can face enablement, written-description, obviousness, and infringement issues.
• A four-capsule regimen is easy to replicate technically.

The strongest practical protection is therefore not manufacturing complexity. It is the combination of FDA-approved indication, prescriber behavior, method-of-use claims, and enforcement against labels or promotional conduct that direct use for cardiovascular-risk reduction.

What formulation and manufacturing barriers remain?

US 10,555,925 does not claim a manufacturing process. It requires a composition with at least approximately 96 weight percent icosapent ethyl among the omega-3 fatty acids and, in claim 4, approximately 1 g in each of four capsules.

The technical requirements for a generic manufacturer include:

• Production of high-purity icosapent ethyl
• Removal or control of DHA and other omega-3 components
• Control of oxidation and peroxide formation
• Consistent capsule fill weight
• Stability through the labeled shelf life
• Bioequivalence to the reference product
• Compliance with FDA current good manufacturing practice requirements

These requirements can create regulatory and quality barriers, but they do not independently prevent generic competition. The generic product does not need to use Amarin’s manufacturing process unless a separate process patent is asserted and valid.

The 96% limitation is important because mixed EPA/DHA products are less likely to satisfy the claim. It also makes compositional testing relevant in litigation.

How does Vascepa compare with competing omega-3 products?

Product or category	Principal omega-3 content	Typical commercial use	Relationship to US 10,555,925
Vascepa	Highly purified icosapent ethyl	Cardiovascular-risk reduction and severe hypertriglyceridemia	Directly implicated
Generic icosapent ethyl	Icosapent ethyl	Label-dependent generic competition	Directly implicated
Lovaza and generic omega-3 acid ethyl esters	EPA plus DHA	Severe hypertriglyceridemia	Usually outside the high-purity limitation
Epanova	Omega-3 carboxylic acids	Development and commercial history distinct from Vascepa	Not a direct substitute for claim coverage
OTC fish oil	Variable EPA, DHA, and other components	Dietary supplement use	Generally outside the claimed composition and indication

The key distinction is that Vascepa uses purified EPA ethyl ester without DHA. That differentiates it from older omega-3 products and supports both the clinical positioning and the patent claim structure.

What revenue exposure does the patent create?

The patent’s revenue exposure is concentrated in the cardiovascular-risk-reduction market rather than the older severe-hypertriglyceridemia market.

Generic entry can affect:

• Branded Vascepa prescription volume
• Net price and rebates
• Payer formulary placement
• Prescriber substitution
• Cardiovascular-use prescriptions filled under generic names
• Royalty or settlement economics
• Amarin’s ability to maintain indication-specific pricing

The economic risk is higher if generic products obtain or effectively capture cardiovascular-use prescriptions through physician prescribing, even when the FDA label omits that indication. It is lower if payers enforce indication-specific coverage and generic manufacturers remain limited to the nonprotected use.

Key Takeaways

• US 10,555,925 is a cardiovascular method-of-use patent, not a molecule patent.
• Claim 1 covers approximately 4 g/day of icosapent ethyl in subjects with established cardiovascular disease to reduce stroke risk.
• Claim 2 narrows protection to baseline triglycerides of approximately 135 to 500 mg/dL and LDL-C of approximately 40 to 100 mg/dL.
• Claims 3 and 4 protect a high-purity composition and the four-capsule, 4 g/day presentation.
• Claim 5 requires at least two years of treatment; claim 6 requires statin therapy.
• The expected expiration is approximately September 22, 2033.
• The patent is relevant to the FDA-approved cardiovascular-risk-reduction indication for Vascepa and to Orange Book-listed method-of-use protection.
• Generic manufacturers can pursue Paragraph IV challenges or section viii label carve-outs.
• Biosimilar risk does not apply because icosapent ethyl is a small molecule.
• The principal enforcement risk is induced infringement through generic labels, promotional materials, or prescribing instructions that direct cardiovascular-risk-reduction use.
• The broader Vascepa patent estate includes overlapping cardiovascular-use, formulation, and product patents, but prior invalidity decisions materially reduce its ability to block all generic competition.

Frequently Asked Questions

Does US 10,555,925 cover all icosapent ethyl prescriptions?

No. It covers a specific method involving approximately 4 g/day, established cardiovascular disease, and stroke-risk reduction. Prescriptions for other conditions or doses may fall outside claim 1.

Does the patent require elevated triglycerides?

No. Claim 1 does not require a triglyceride range. Elevated triglycerides are added by claim 2.

Does a generic need four 1 g capsules to infringe?

No. Four 1 g capsules are required only by claim 4. A different dosage presentation could still implicate broader claims if the other elements are met.

Are Lovaza generics direct substitutes for the claimed method?

Generally no. Lovaza-type products contain EPA and DHA mixtures, while claim 3 requires icosapent ethyl to comprise at least approximately 96 weight percent of all omega-3 fatty acids in the composition.

Can a generic market icosapent ethyl before 2033?

Potentially yes. Entry can occur through a successful Paragraph IV challenge, a settlement, a section viii label carve-out, or another outcome that avoids infringement of enforceable claims.

Is the patent vulnerable because stroke reduction is a clinical outcome?

The outcome limitation can create litigation issues involving claim construction, proof of intent, enablement, and infringement. REDUCE-IT clinical evidence provides substantial support for the claimed cardiovascular-risk-reduction use, but it does not eliminate ordinary validity and infringement challenges.

References

1. Bhatt, D. L., Steg, P. G., Miller, M., et al. (2019). Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia. New England Journal of Medicine, 380(1), 11-22.

2. U.S. Food and Drug Administration. (2019). FDA approves use of drug to reduce risk of cardiovascular events in adults with elevated triglyceride levels. FDA.

3. U.S. Food and Drug Administration. (2024). Vascepa (icosapent ethyl) prescribing information. FDA.

4. U.S. Patent and Trademark Office. (2020). U.S. Patent No. 10,555,925: Methods of reducing cardiovascular risk using icosapent ethyl. USPTO.

5. Amarin Pharma, Inc. v. Hikma Pharmaceuticals USA Inc., 24 F.4th 1368 (Fed. Cir. 2022).

6. U.S. Food and Drug Administration. (2024). Abbreviated new drug application approvals and patent certifications under the Hatch-Waxman Amendments. FDA.

Drugs Protected by US Patent 10,555,925

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Amarin Pharms	VASCEPA	icosapent ethyl	CAPSULE;ORAL	202057-001	Jul 26, 2012	AB	RX	Yes	Yes						USE OF VASCEPA AS AN ADJUNCT TO STATIN THERAPY TO REDUCE THE RISK OF STROKE IN AN ADULT PATIENT WITH ESTABLISHED CARDIOVASCULAR DISEASE
Amarin Pharms	VASCEPA	icosapent ethyl	CAPSULE;ORAL	202057-002	Feb 16, 2017	AB	RX	Yes	No						USE OF VASCEPA AS AN ADJUNCT TO STATIN THERAPY TO REDUCE THE RISK OF STROKE IN AN ADULT PATIENT WITH ESTABLISHED CARDIOVASCULAR DISEASE

International Family Members for US Patent 10,555,925

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2013282394
Australia	2018204499
Australia	2020294210
Brazil	112014032905
Canada	2877514