United States Drug Patent 6,562,826: Scope, Claims, Expiration, and Ranolazine Patent Landscape

US Patent No. 6,562,826 protected methods of treating angina and arrhythmias with sustained-release ranolazine formulations. Its core limitations were a high ranolazine loading, controlled plasma exposure over 24 hours, and defined peak-to-trough, peak-concentration, and trough-concentration parameters. The patent was directed to treatment methods rather than ownership of ranolazine itself or every extended-release ranolazine tablet.

The patent issued June 17, 2003, from an application claiming priority to an earlier ranolazine filing. Its statutory term expired in 2020 based on the earliest claimed priority date. It therefore no longer creates a current United States blocking right against generic ranolazine products. During its term, however, it was commercially important because FDA-approved Ranexa relied on sustained-release ranolazine pharmacokinetics consistent with the claimed ranges.

What does US Patent 6,562,826 protect?

US 6,562,826 protects treatment methods using sustained-release ranolazine dosage forms that produce controlled plasma exposure during a 24-hour period.

The claims divide into five technical groups:

Claim group	Principal limitation	Claims
Peak-to-trough control	Ratio does not exceed 4:1, 3:1, or 2:1	1-3, 10-12, 19-22, 23-26
Trough concentration	Minimum trough level of about 850 ng base/mL	4, 6, 7, 13, 15, 17, 18
Peak concentration	Maximum peak level of about 4,000 ng base/mL	8-9
High drug loading	At least 50% ranolazine, or about 70%-80% ranolazine	1, 10, 14, 16, 19, 23
Binder and plasma-range limitations	pH-dependent plus pH-independent binders and 850-4,000 ng base/mL exposure	16, 18

The claims generally require both a therapeutic use and a pharmacokinetic result. A tablet would not necessarily infringe merely because it contains ranolazine or is labeled as extended release. The relevant method claim would require administration to a patient in a manner that produces the claimed pharmacokinetic profile.

What are the independent claims in US 6,562,826?

The principal independent claims are claims 1, 4-10, 13-19, and 23. Their scope is summarized below.

Claim	Required treatment or formulation feature	Key numerical limitation
1	Sustained-release ranolazine for variant and exercise-induced angina	At least 50% ranolazine; peak-to-trough ratio no more than 4:1
4	Sustained-release ranolazine for angina	Trough at least about 850 ng base/mL
5	Sustained-release ranolazine for cardiovascular disease	Maintains levels close to minimum effective levels without peak fluctuation
6	Sustained and continuous gastrointestinal release	Trough at least about 850 ng base/mL
7	Immediate-release loading dose followed by or combined with sustained release	Trough at least about 850 ng base/mL
8	Sustained-release ranolazine for angina	Peak no more than about 4,000 ng base/mL
9	Immediate-release loading dose plus sustained release	Peak no more than about 4,000 ng base/mL
10	Sustained-release ranolazine for angina	About 70%-80% ranolazine; peak-to-trough no more than 4:1
13	Sustained-release ranolazine for angina	Trough at least about 850 ng base/mL
14	Sustained-release ranolazine for cardiovascular disease	About 70%-80% ranolazine
15	Ranolazine formulation for angina	Trough at least about 850 ng base/mL
16	Sustained-release formulation with two binder types	At least 50% ranolazine; 850-4,000 ng base/mL for at least 24 hours
17	Sustained-release ranolazine for angina	850-4,000 ng base/mL for at least 24 hours
18	Sustained-release formulation with two binder types	850-4,000 ng base/mL for at least 24 hours
19	Sustained-release ranolazine for angina in a mammal	At least 50% ranolazine; peak-to-trough no more than 4:1
23	Sustained-release ranolazine for arrhythmia in a mammal	At least 50% ranolazine; peak-to-trough no more than 4:1

Claims 2, 3, 11, 12, 21, 22, 25, and 26 narrow the peak-to-trough ratio to 3:1 or 2:1. Those limitations are commercially narrower because they require a more uniform 24-hour plasma profile.

How should the patent’s claim scope be construed?

The patent’s practical scope depends on five claim elements.

1. Sustained-release administration

Most claims require a sustained-release dosage form. The claims describe slow and continuous release while the formulation passes through the stomach and gastrointestinal tract. A conventional immediate-release ranolazine product, standing alone, would not satisfy this limitation.

Claims 7 and 9 are broader in administration design because they expressly cover an immediate-release formulation used with, or followed by, a sustained-release dosage form. This protects a loading-dose strategy intended to achieve therapeutic concentrations quickly while maintaining exposure through the extended-release product.

2. Ranolazine loading

Claims 1, 4, 10, 14, 16, 19, and 23 contain explicit ranolazine-loading limitations. The broad loading threshold is at least 50% by weight. Claims 10 and 14 narrow this to approximately 70%-80% by weight.

The loading limitation is measured against the dosage form, not merely the active pharmaceutical ingredient’s presence in the product. Excipients, binders, coatings, lubricants, and other inactive ingredients reduce the percentage by weight.

3. Peak-to-trough ratio

The peak-to-trough limitation is a pharmacokinetic limitation:

[ \text{Peak-to-trough ratio} = \frac{\text{maximum plasma ranolazine concentration}}{\text{minimum plasma ranolazine concentration}} ]

A claim requiring a ratio no greater than 4:1 is potentially satisfied by a ratio of 4:1 or lower. Claims requiring no greater than 3:1 or 2:1 are progressively narrower.

The ratio is measured over a 24-hour period. The claim does not merely describe a product dissolution profile. It requires a plasma result in a human patient for claims directed to human treatment.

4. Absolute plasma concentrations

The patent uses two key concentration thresholds:

Trough: about 850 ng base/mL or higher.
Peak: about 4,000 ng base/mL or lower.

Claims 16-18 combine these values into an exposure window of approximately 850-4,000 ng base/mL for at least 24 hours. The use of "about" creates a potential claim-construction issue. Courts generally interpret such terms in light of the specification, examples, measurement variability, and technical meaning at the filing date.

The claims refer to ranolazine concentrations expressed as ranolazine base. A formulation using a ranolazine salt would ordinarily require conversion to the equivalent ranolazine-base amount when assessing the claimed concentration.

5. Disease and patient limitations

The principal human-treatment claims are limited to variant and exercise-induced angina. Claims 19-22 expand the mammalian angina coverage, while claims 23-26 address arrhythmias in mammals.

A product label for chronic angina would not automatically establish infringement. A method claim requires proof that the accused product is intended, promoted, prescribed, or used for the claimed disease and that the claimed formulation and pharmacokinetic limitations are met.

Which claims are strongest commercially?

The strongest commercial claims were likely the claims combining objective formulation and pharmacokinetic limitations.

Claim type	Commercial strength	Main vulnerability
At least 50% ranolazine plus 4:1 ratio	Moderate	Potential design-around through loading, dosing, or PK profile
70%-80% ranolazine plus 4:1 ratio	Moderate to strong	Narrow composition range and testing burden
Trough at least 850 ng/mL	Moderate	Patient-to-patient variability and assay methodology
Peak no more than 4,000 ng/mL	Moderate	Requires reliable clinical or bioequivalence data
850-4,000 ng/mL for 24 hours	Stronger combination claim	Difficult proof of continuous patient exposure
pH-dependent and pH-independent binders	Narrow but technically specific	Formulation records and binder classification become central
2:1 peak-to-trough ratio	Narrowest	More difficult to satisfy and easier to avoid

Claims 16 and 18 have narrower but potentially more defensible formulation scope because they require an admixture of at least one pH-dependent binder and at least one pH-independent binder. A generic manufacturer could avoid those claims by using a different release-control architecture, although that would not necessarily avoid the broader pharmacokinetic claims.

What formulations are protected by US 6,562,826?

The patent covers sustained-release ranolazine formulations with a high active loading and controlled release over the gastrointestinal transit period. The claims are compatible with tablets, matrix systems, or other oral sustained-release dosage forms, provided the formulation meets the express claim limitations.

The binder limitations in claims 16 and 18 are significant:

A pH-dependent binder changes binding or release behavior depending on gastrointestinal pH.
A pH-independent binder retains binding or release-control characteristics across the relevant pH range.
The claim requires an admixture of both types.

The claims do not appear to require a particular named polymer in the claim language supplied. A named polymer disclosed in the specification would not necessarily be a claim limitation unless incorporated into the issued claims.

The patent does not broadly claim:

Every ranolazine composition.
Every ranolazine salt.
Every immediate-release ranolazine product.
Every sustained-release product regardless of plasma exposure.
Ranolazine as a chemical compound.
A manufacturing process for ranolazine itself.

When did US Patent 6,562,826 expire?

US 6,562,826 expired in 2020 under the ordinary United States patent-term framework. The relevant term was measured from the earliest effective nonprovisional filing date, subject to any patent-term adjustment or extension reflected in the official USPTO record. The patent therefore cannot presently block a generic ranolazine launch on the basis of ordinary patent rights.

Event	Date or period
Patent issued	June 17, 2003
Patent term basis	20 years from applicable earliest nonprovisional filing date
Expected statutory expiration	2020
Current enforceability	Expired by term
Current generic blocking effect	None from this patent alone

Patent expiration does not erase historical infringement exposure for conduct occurring before expiration. It ends the right to obtain prospective exclusion after the expiration date.

What was the FDA and Orange Book status of Ranexa?

Ranexa is the branded extended-release formulation of ranolazine marketed by CV Therapeutics and later controlled by Gilead Sciences. FDA approved Ranexa extended-release tablets under NDA 021526 for chronic angina. The approved labeling used twice-daily administration, with a recommended starting dose of 500 mg twice daily and an increase to 1,000 mg twice daily when clinically indicated, subject to tolerability and labeling restrictions. [2]

The FDA Orange Book historically listed ranolazine-related patents associated with Ranexa. Orange Book listing is important because an abbreviated new drug application applicant must address listed patents through a certification under section 505(j) of the Federal Food, Drug, and Cosmetic Act. A Paragraph IV certification can trigger patent litigation and, in qualifying circumstances, a 30-month stay of approval. [3]

The Orange Book listing of a patent does not establish that every listed claim is valid or infringed. It identifies patents submitted by the NDA holder or patent owner as covering the drug, formulation, or approved method of use.

Did US 6,562,826 create Paragraph IV risk for generic ranolazine?

Yes, during its unexpired term. A generic applicant seeking approval for an extended-release ranolazine product could have faced several possible patent positions:

The generic formulation infringes a sustained-release formulation or method claim.
The proposed labeling induces infringement of a patented angina or arrhythmia method.
The generic product does not meet the claimed 50% or 70%-80% ranolazine loading.
The generic product does not produce the claimed 850-4,000 ng/mL exposure window.
The generic product produces a peak-to-trough ratio above the claimed threshold.
The formulation omits the claimed combination of pH-dependent and pH-independent binders.

A Paragraph IV challenge would have required invalidity, unenforceability, or noninfringement positions. The most plausible technical defenses would have focused on:

Failure to meet the claimed plasma thresholds.
Different peak-to-trough behavior.
Drug loading outside the claimed range.
Absence of the required binder combination.
Lack of induced infringement based on a permitted label.
Anticipation or obviousness based on prior sustained-release ranolazine and anti-angina disclosures.

Because the patent is expired, Paragraph IV certification to this patent no longer creates a current launch barrier.

What patent litigation affected ranolazine generic entry?

Ranolazine generic-entry disputes centered on the broader Ranexa patent estate rather than US 6,562,826 in isolation. The relevant litigation analysis must distinguish:

Compound patents.
Sustained-release formulation patents.
Method-of-treatment patents.
Orange Book-listed patents.
Regulatory exclusivity.
Settlement agreements and agreed generic-entry dates.

The existence of a Paragraph IV filing does not prove that litigation proceeded to judgment. Likewise, a settlement does not establish validity or infringement. The operative business question is the earliest legally permitted generic launch date under the settlement, court order, patent expiration, and FDA approval status.

By the time the key ranolazine patents expired around 2019-2020, the commercial significance of US 6,562,826 had declined. Generic ranolazine extended-release products entered the market after expiration of the relevant blocking patents and regulatory barriers. The patent therefore has historical litigation importance but no meaningful present-day exclusionary value.

How does US 6,562,826 compare with the broader Ranexa patent estate?

US 6,562,826 was a method patent. It should be analyzed separately from ranolazine formulation patents, including the sustained-release formulation family associated with Ranexa.

Estate category	Typical protection	Relevance to generic launch
Chemical compound patents	Ranolazine molecule or related compounds	Potentially broad but generally expired earlier
Sustained-release formulation patents	Matrix, excipient, release rate, or tablet design	Direct product-design risk
Method patents	Angina, arrhythmia, or cardiovascular treatment	Label and induced-infringement risk
PK-profile claims	Peak, trough, and peak-to-trough exposure	Bioequivalence and infringement-testing risk
Manufacturing patents	Granulation, compression, coating, or process steps	Depends on actual generic manufacturing
Regulatory exclusivity	FDA approval exclusivity	Separate from patent term

The principal strategic distinction is that 6,562,826 does not prevent all extended-release ranolazine products. It targets products and treatment regimens that produce specified exposure characteristics in specified patient populations.

How strong was the patent estate?

The patent was commercially meaningful but technically narrow.

Strengths

The claims tied treatment to measurable plasma concentrations.
The 850-4,000 ng/mL range corresponded to the intended therapeutic exposure profile.
High ranolazine loading could limit formulation design options.
Claims covered both angina and, in the mammalian claims, arrhythmia treatment.
Dependent claims created multiple narrower positions around 2:1 and 3:1 ratios.

Weaknesses

The claims were method claims, not broad composition claims.
Human pharmacokinetic results can vary by patient, dose, food intake, hepatic function, renal function, and interacting drugs.
"About" and "minimum" concentration terms create measurement and claim-construction disputes.
A generic could attempt a formulation or labeling design-around.
The patent term expired in 2020.
The claims required proof of both disease treatment and a pharmacokinetic outcome.

The patent was strongest against a product that reproduced the branded Ranexa formulation, used the same dosing regimen, and generated the claimed exposure profile. It was weaker against a product with materially different drug loading, release mechanism, dosing instructions, or pharmacokinetic profile.

What generic launch scenarios existed?

During the patent term, generic launch scenarios included:

Scenario	Business result
Paragraph IV victory	Potential launch before patent expiry, subject to FDA approval and other patents
Noninfringement through altered PK profile	Possible launch if no other blocking patents remained
Formulation design-around	Reduced risk under binder or loading claims
Authorized generic	Commercial entry controlled by the brand owner
Settlement with delayed entry	Entry date governed by agreement and regulatory approval
Launch after all relevant patents expired	Lowest patent-litigation risk

After 2020, the principal risks shifted from patent exclusion to ordinary generic competition, FDA approval timing, manufacturing capacity, pricing, and market share.

What is the current commercial value of US 6,562,826?

The patent has no current standalone blocking value because its term has expired. Its historical value was linked to Ranexa’s extended-release product and the difficulty of demonstrating noninfringing controlled exposure during the patent term.

Current commercial analysis should focus on:

Number of approved generic ranolazine ER suppliers.
Wholesale acquisition cost and reimbursement.
Generic substitution rates.
Brand retention and authorized-generic arrangements.
Remaining formulation know-how and manufacturing scale.
Any surviving patents unrelated to US 6,562,826.

There is no biosimilar pathway for ranolazine because ranolazine is a chemically synthesized small molecule. Competitive entry proceeds through the ANDA pathway, not the abbreviated biologics license application pathway.

Key Takeaways

US 6,562,826 protected treatment methods using sustained-release ranolazine.
Its central parameters were at least 50% ranolazine loading, a peak-to-trough ratio no greater than 4:1, a trough of about 850 ng base/mL, and a peak of about 4,000 ng base/mL.
Claims 16 and 18 added a specific admixture of pH-dependent and pH-independent binders.
The patent covered methods, not ranolazine as a molecule or every extended-release ranolazine formulation.
The patent expired in 2020 and no longer blocks generic ranolazine entry.
Historical Paragraph IV risk depended on the entire Ranexa patent estate, not this patent alone.
The principal technical design-arounds involved drug loading, release architecture, plasma exposure, dosing instructions, and binder selection.
Ranolazine is a small-molecule product with generic, not biosimilar, competition.

FAQs

Does US 6,562,826 cover Ranexa itself?

It covered certain methods of using sustained-release ranolazine formulations consistent with defined loading and plasma-exposure parameters. It did not claim every Ranexa tablet as a composition.

Could a generic ranolazine tablet infringe the patent during its term?

Yes, if the product, labeling, administration method, patient population, and resulting pharmacokinetic profile satisfied an asserted claim. A product containing ranolazine alone would not be sufficient.

What ranolazine plasma level did the patent treat as therapeutically relevant?

Several claims required a trough concentration of at least about 850 ng base/mL. Other claims required maintenance within approximately 850-4,000 ng base/mL for at least 24 hours.

Did the patent cover once-daily ranolazine dosing?

The claims generally required administration over a 24-hour period and included language covering administration at least once during that period. The claim language therefore focused on 24-hour exposure rather than imposing a universal once-daily dosing requirement.

Is a ranolazine biosimilar possible?

No. Ranolazine is a small-molecule active ingredient. Competing products use the FDA ANDA generic-drug pathway rather than the biosimilar pathway.

References

United States Patent and Trademark Office. (2003). US Patent No. 6,562,826, Methods of treating angina using ranolazine. U.S. Department of Commerce.
U.S. Food and Drug Administration. (2023). Ranexa (ranolazine) extended-release tablets: Prescribing information. FDA.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations. FDA.
U.S. Code, 35 U.S.C. §§ 154, 271, 282, 283, 284, 285.
U.S. Food and Drug Administration. (2024). Orange Book: Approved drug products with therapeutic equivalence evaluations, patent and exclusivity information. FDA.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	1109558	⤷ Start Trial	PA2008017	Lithuania	⤷ Start Trial
European Patent Office	1109558	⤷ Start Trial	CA 2008 00051	Denmark	⤷ Start Trial
European Patent Office	1109558	⤷ Start Trial	91504	Luxembourg	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 6,562,826

Summary for Patent: 6,562,826