United States Patent 6,620,814: Ranolazine Claims, Expiration, Litigation and Generic Patent Landscape

U.S. Patent No. 6,620,814 covered methods of treating cardiovascular disease with sustained-release ranolazine using pharmacokinetic targets, including plasma concentrations of approximately 550 to 7,500 ng base/mL and peak-to-trough ratios of no more than 4:1, 3:1, or 2:1. The patent was assigned to CV Therapeutics and later became part of Gilead Sciences’ Ranexa patent estate. Its listed patent term expired on August 26, 2019. The patent therefore has no remaining enforceable exclusionary term in the United States. Ranexa’s principal FDA-listed patent estate consisted of U.S. Patent Nos. 6,620,814 and 6,303,607, both of which have expired.[1][2]

What does U.S. Patent 6,620,814 protect?

U.S. Patent 6,620,814 protects therapeutic methods rather than a ranolazine molecule, a specific tablet design, or a manufacturing process. Its central inventive concept is the use of sustained-release ranolazine to maintain relatively stable plasma exposure over a 24-hour period.

The claims combine four recurring limitations:

Administration of ranolazine to a human or mammal.
Treatment of specified cardiovascular diseases.
Use of a sustained-release dosage form in most claims.
Achievement of defined pharmacokinetic results.

The principal pharmacokinetic parameters are:

Parameter	Claimed threshold
Ranolazine plasma concentration	About 550 to about 7,500 ng base/mL
Minimum trough concentration	About 550 ng base/mL
Maximum peak concentration	About 7,500 ng base/mL, or 5,000 ng base/mL in claim 10
Peak-to-trough ratio	No more than 4:1
Narrower peak-to-trough ratio	Less than or equal to 3:1
Narrowest peak-to-trough ratio	Less than or equal to 2:1
Ranolazine content	At least 50% by weight; claims 11 and 15 require approximately 70% to 80%
Dosing interval	At least once during a 24-hour period

The claims address arrhythmias, variant angina, exercise-induced angina, myocardial infarction, and angina more generally. Claims 5 through 19 focus heavily on variant and exercise-induced angina.

How broad are the independent claims in U.S. Patent 6,620,814?

Claims 1, 2, 5, 6, 7, 8, 9, 10, and 14 are independent claims directed to human treatment methods. Claims 17 through 19 add formulation and pharmacokinetic limitations. Claims 20 and 24 are independent claims directed to treating angina and arrhythmias in a mammal.

Claim 1: concentration-window method

Claim 1 requires:

A human patient;
One of the listed cardiovascular diseases;
A sustained-release ranolazine dosage form;
At least 50% ranolazine by weight; and
Plasma ranolazine levels of approximately 550 to 7,500 ng base/mL for at least 24 hours.

This is a relatively broad method claim because it does not require a particular tablet geometry, polymer, coating, dose strength, or dosing frequency. A competing product could fall within the claim based on its clinical pharmacokinetic profile even if its formulation technology differs from the disclosure.

The claim has two important constraints. First, the dosage form must contain at least 50% ranolazine by weight. Second, the required plasma concentration must be maintained for at least 24 hours. A formulation that produces the claimed concentration only briefly would not satisfy the express temporal limitation.

Claim 2: peak-to-trough control

Claim 2 requires sustained-release ranolazine with at least 50% ranolazine by weight and a peak-to-trough plasma ratio no greater than 4:1 over 24 hours.

This claim shifts the focus from an absolute plasma concentration range to exposure uniformity. Claims 3 and 4 narrow the ratio to less than 3:1 and less than 2:1, respectively.

A generic formulation could potentially avoid literal infringement if its validated pharmacokinetic profile consistently exceeds the claimed ratio. That analysis would depend on the claim construction of “over the 24 hour period,” the relevant patient population, dose, fed or fasted state, and the statistical method used to determine peak and trough values.

Claim 5: minimum trough concentration

Claim 5 requires treatment of variant or exercise-induced angina with a sustained-release dosage form that maintains a trough concentration of approximately 550 ng base/mL during the 24-hour period.

This claim does not expressly require the 50% ranolazine-by-weight limitation. Its principal limitations are the disease indication, sustained-release dosage form, and minimum trough level.

Claims 6 and 15: reduced fluctuation

Claims 6 and 15 describe maintaining plasma ranolazine near minimal effective levels without peak fluctuations. Claim 15 adds a ranolazine content of approximately 70% to 80% by weight.

These claims contain functional language. Their scope would depend on how “close to minimal effective levels” and “without peak fluctuations” are construed. The claims are commercially important because high-drug-load sustained-release tablets are commonly used to deliver ranolazine, but their enforceability would have depended on proving that the accused product achieved the stated pharmacokinetic objective.

Claims 7 and 9: gastrointestinal release profile

Claims 7 and 9 require a formulation that releases ranolazine slowly and continuously as it passes through the stomach and gastrointestinal tract.

Claim 7 requires maintenance of a trough concentration of at least approximately 550 ng base/mL. Claim 9 requires a peak concentration no greater than approximately 7,500 ng base/mL.

These limitations are directed to in vivo performance, not merely to a dissolution specification. A formulation could have a similar in vitro dissolution profile yet avoid the claim if it did not produce the required plasma profile. Conversely, a different release mechanism could still raise infringement issues if it delivered the same claimed result.

Claims 8 and 10: immediate-release loading followed by sustained release

Claims 8 and 10 cover a two-stage treatment approach:

Immediate-release ranolazine to reach a therapeutic level rapidly; and
Sustained-release ranolazine to maintain exposure.

Claim 8 requires a trough of at least approximately 550 ng base/mL. Claim 10 limits the peak to approximately 5,000 ng base/mL.

These claims are narrower than claims directed solely to sustained release because they require an immediate-release component used in combination with, or followed by, a sustained-release dosage form.

What formulation features are protected by Patent 6,620,814?

The patent does not require a single named polymer, tablet coating, excipient, compression process, or release matrix in the claims provided. The formulation-related claims instead use structural and functional requirements.

Formulation feature	Claims implicated	Scope
Sustained-release dosage form	1, 2, 5-15, 17-20, 24	Broad dosage-form limitation
At least 50% ranolazine by weight	1, 2, 6, 20, 24	High-drug-load requirement
Approximately 70% to 80% ranolazine	11-13, 15	Narrower high-drug-load limitation
pH-dependent and pH-independent binders	17, 19	Specific excipient combination
Slow, continuous gastrointestinal release	7, 9	Functional release limitation
Immediate-release plus sustained-release administration	8, 10	Loading and maintenance regimen
24-hour exposure	Most independent claims	Temporal and pharmacokinetic limitation

Claims 17 and 19 specifically require an admixture of at least one pH-dependent binder and at least one pH-independent binder. Those claims are narrower than the main pharmacokinetic claims because an accused product would need to satisfy both the excipient limitation and the plasma-level limitation.

How do the dependent claims narrow the patent scope?

Claims 3, 4, 12, 13, 22, 23, 26, and 27 narrow the peak-to-trough ratio.

Parent claim	Dependent claim	Required ratio
Claim 2	Claim 3	Less than 3:1
Claim 2	Claim 4	Less than 2:1
Claim 11	Claim 12	No more than 3:1
Claim 11	Claim 13	No more than 2:1
Claim 20	Claim 22	No more than 3:1
Claim 20	Claim 23	No more than 2:1
Claim 24	Claim 26	No more than 3:1
Claim 24	Claim 27	No more than 2:1

The dependent claims create fallback positions but do not materially change the patent’s basic strategy. The patent seeks protection for stable 24-hour exposure, first at a 4:1 ratio and then at progressively narrower ratios.

When did U.S. Patent 6,620,814 lose exclusivity?

The patent’s listed expiration date was August 26, 2019.[1] After that date:

The method claims ceased to provide enforceable U.S. patent exclusivity.
A generic ranolazine manufacturer no longer needed a license to practice the expired claims.
Post-expiration sales could not ordinarily be enjoined based on this patent.
Any surviving claim would remain subject to ordinary issues such as claim construction, validity, and past damages, but the prospective exclusionary term ended.

Patent expiration did not remove Ranexa from the FDA-approved drug market. It removed the patent barrier to competing ranolazine products.

What was the Orange Book status of Ranexa?

Ranexa, the branded ranolazine extended-release product, was approved by the FDA under NDA 021526 on January 27, 2006. The approved product included 500 mg and 1,000 mg extended-release tablets for chronic angina.[3]

The principal Orange Book-listed Ranexa patents were:

Patent	General subject matter	Listed expiration
U.S. 6,303,607	Ranolazine compositions and methods of use	March 16, 2020
U.S. 6,620,814	Sustained-release ranolazine treatment methods	August 26, 2019

U.S. Patent 6,303,607 was directed to ranolazine composition and use concepts and extended beyond the expiration of U.S. Patent 6,620,814. Its later expiration date was commercially significant because it remained the principal listed patent barrier after the ’814 patent expired.[1][2]

FDA Orange Book listings do not establish that every claim is valid or infringed. They identify patents submitted by the NDA holder and relevant to the approved drug or method of use.

Which companies challenged Ranexa exclusivity?

Generic manufacturers challenged the Ranexa patent estate through abbreviated new drug application certifications, including Paragraph IV certifications. Public Hatch-Waxman records and FDA approval actions identify generic activity involving companies such as Lupin, Teva, and other ANDA sponsors during the period preceding generic entry.[3][4]

The commercial issue was not whether generic ranolazine could be chemically manufactured. The issue was whether a generic applicant could obtain approval before the Orange Book-listed patents expired or through a settlement date.

Paragraph IV litigation generally creates a 30-month FDA approval stay when the NDA holder timely sues the ANDA applicant. The stay can end earlier through court action, settlement, or patent expiration. The final market-entry date depends on the relevant settlement terms, court orders, pediatric exclusivity, and the applicant’s regulatory status.

What patent litigation affected Ranexa?

Ranexa litigation centered on the two principal Orange Book patents rather than on a broad patent thicket involving dozens of active patents.

The typical disputes involved:

Whether an ANDA product practiced the claimed extended-release formulation or treatment method;
Whether the asserted claims were invalid for anticipation or obviousness;
Whether the generic applicant’s proposed labeling induced infringement;
Whether the FDA-listed method-of-use patents remained relevant to the proposed label; and
Whether settlement agreements delayed generic launch.

Gilead acquired CV Therapeutics in 2009 for approximately $1.4 billion, bringing Ranexa and its associated patent rights into Gilead’s portfolio.[5] Gilead subsequently managed the branded Ranexa product and related generic patent disputes.

By the time U.S. Patent 6,620,814 expired in August 2019, its prospective litigation value had ended. The remaining commercial patent question concerned U.S. Patent 6,303,607, which expired in March 2020.

Were there settlement agreements involving Ranexa generics?

Ranexa Paragraph IV cases were resolved through litigation activity and settlement arrangements before broad generic availability. Hatch-Waxman settlements can include:

A defined generic launch date;
A license beginning before patent expiration;
A no-acceleration clause;
Restrictions on authorized generic competition; and
Resolution of patent claims without a final validity judgment.

Settlement terms are material because a generic applicant may launch under a license before the listed patent expiration date even if the patent remains formally in force. The existence of a settlement does not establish patent validity or infringement.

For U.S. Patent 6,620,814, the critical commercial fact is that all settlement-based delay tied to the patent ended no later than its August 26, 2019 expiration date.

What was the FDA generic status of ranolazine?

FDA-approved generic ranolazine extended-release tablets entered the U.S. market after the expiration period for the principal Ranexa patents. Lupin received FDA approval for ranolazine extended-release tablets in 2019, covering strengths corresponding to the branded product.[6]

The generic product competes with Ranexa through the ANDA pathway. An ANDA relies on the branded product’s safety and efficacy findings and must demonstrate pharmaceutical equivalence and bioequivalence. It does not require a new clinical efficacy program equivalent to the original NDA.

Because ranolazine is a small-molecule drug, biosimilar approval is not relevant. The applicable competitive pathway is generic substitution through an ANDA, not a biologics license application or biosimilar application.

How strong was the patent estate for ranolazine?

The estate was commercially meaningful before 2020 but structurally limited compared with estates for many newer specialty drugs.

Strength factor	Assessment
Core composition protection	Limited to the scope and term of U.S. 6,303,607
Sustained-release method protection	Broad pharmacokinetic coverage under U.S. 6,620,814
Formulation protection	Dependent on high drug load, binders, and release behavior
Method-of-use coverage	Focused on angina, arrhythmia, myocardial infarction, and plasma exposure
Manufacturing protection	Not the principal subject of the ’814 claims
Geographic coverage	U.S. only for U.S. Patent 6,620,814
Remaining U.S. term	None after August 26, 2019
Biosimilar barrier	Not applicable
Generic substitution risk	High after 2019-2020 patent expirations

The ’814 patent had practical strength while it was in force because its method claims could reach products based on clinical pharmacokinetic performance, even where formulation composition differed. Its weakness was that the claims depended on measurable patient exposure and disease-treatment facts. Those facts can create evidentiary complexity in an infringement case.

What generic launch risks applied to a ranolazine extended-release product?

Before expiration, a generic applicant faced several potential risks:

Literal infringement risk. A product could meet the sustained-release, high-drug-load, and plasma-ratio limitations.
Induced-infringement risk. A proposed label could instruct treatment of chronic angina or other claimed conditions.
Pharmacokinetic variability. Peak and trough ratios can vary by dose, food, patient characteristics, hepatic function, and sampling design.
Formulation overlap. A high-drug-load matrix using pH-dependent and pH-independent binders could implicate claims 17 and 19.
Regulatory timing risk. Patent expiration, Paragraph IV litigation, settlement provisions, and FDA approval timing could produce different launch dates.
Commercial price erosion. Multiple ANDA approvals could rapidly reduce branded ranolazine prices after the final patent barrier expired.

After August 26, 2019, the ’814 patent no longer created prospective launch risk. After March 16, 2020, the core Orange Book patent estate identified for Ranexa also had expired.

How does U.S. Patent 6,620,814 compare with U.S. Patent 6,303,607?

Issue	U.S. 6,620,814	U.S. 6,303,607
Primary focus	Treatment method and plasma exposure	Ranolazine compositions and methods of use
Key technology	Sustained-release administration	Ranolazine dosage-form and therapeutic concepts
Pharmacokinetic limitations	Central to many claims	Less central to the ’814 claim structure
High ranolazine loading	At least 50%; some claims 70%-80%	Relevant to disclosed composition concepts
Expiration	August 26, 2019	March 16, 2020
Generic relevance	Method-of-use and performance risk	Core Orange Book patent barrier
Current status	Expired	Expired

The ’814 patent was the more explicit pharmacokinetic patent. The ’607 patent was the later-expiring core patent and therefore had greater importance for the final U.S. generic-entry timeline.

Key Takeaways

U.S. Patent 6,620,814 covered sustained-release ranolazine treatment methods, not a standalone ranolazine compound.
The core claim strategy required 24-hour plasma exposure within defined concentration or peak-to-trough parameters.
Claims covered at least 50% ranolazine by weight, with narrower claims covering 70% to 80%.
Claims 17 and 19 required both pH-dependent and pH-independent binders.
The patent’s listed expiration date was August 26, 2019.
Ranexa’s other principal Orange Book patent, U.S. 6,303,607, expired March 16, 2020.
Paragraph IV activity and settlement agreements affected the timing of generic ranolazine entry.
Generic ranolazine competes through the ANDA pathway; biosimilar risk does not apply.
U.S. Patent 6,620,814 currently presents no prospective patent barrier to generic extended-release ranolazine.

FAQs About U.S. Patent 6,620,814 and Ranexa Exclusivity

Does U.S. Patent 6,620,814 still block generic ranolazine?

No. Its listed U.S. patent term expired on August 26, 2019.

Did U.S. Patent 6,620,814 cover the Ranexa chemical compound?

No. The claims provided are directed to methods of administering ranolazine, particularly sustained-release treatment methods with specified plasma exposure.

Could an immediate-release ranolazine product infringe the ’814 patent?

Claims 8 and 10 expressly address immediate-release ranolazine used with or followed by sustained-release ranolazine. An immediate-release-only product would not satisfy those claim limitations.

Is a ranolazine extended-release tablet protected by a biosimilar patent strategy?

No. Ranolazine is a small-molecule drug. Competition proceeds through generic-drug regulation under the ANDA pathway.

What was the most commercially important Ranexa patent after the ’814 patent expired?

U.S. Patent 6,303,607, which had a listed expiration date of March 16, 2020, was the later-expiring principal Orange Book patent for Ranexa.

References

U.S. Patent and Trademark Office. (2003). U.S. Patent No. 6,620,814: Methods of treating cardiovascular diseases with ranolazine.
U.S. Food and Drug Administration. (2020). Approved drug products with therapeutic equivalence evaluations: Orange Book, NDA 021526, Ranexa.
U.S. Food and Drug Administration. (2006). NDA 021526: Ranexa (ranolazine) extended-release tablets approval history and labeling.
U.S. Food and Drug Administration. (2024). Paragraph IV patent certifications and abbreviated new drug application records.
Gilead Sciences, Inc. (2009). Gilead completes acquisition of CV Therapeutics.
Lupin Pharmaceuticals, Inc. (2019). FDA approval of ranolazine extended-release tablets.

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
European Patent Office	1109558	⤷ Start Trial	PA2008017,C1109558	Lithuania	⤷ Start Trial
European Patent Office	1109558	⤷ Start Trial	09C0001	France	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 6,620,814

Summary for Patent: 6,620,814