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Patent landscape, scope, and claims: |
United States Patent 6,852,724: Scope, Claims, and U.S. Patent Landscape for Sustained-Release Ranolazine
What does U.S. Patent 6,852,724 claim at a high level?
U.S. Patent 6,852,724 (the “’724 patent”) claims methods that treat defined cardiovascular conditions by administering ranolazine via sustained-release (SR) pharmaceutical dosage forms. The core claim architecture is built around four technical anchors:
- Dosage form composition: SR dosage form comprises at least 50% by weight ranolazine.
- PK/PD control via trough and peak-to-trough ratios: SR dosing limits peak-to-trough plasma ranolazine ratio (3:1 or 4:1 depending on the claim) over a 24-hour period and/or maintains a trough around 850 ng base/mL.
- Treatment scope: angina (variant and exercise-induced), intermittent claudication, myocardial infarction, cardiovascular disease broadly, arrhythmias.
- Administration mode: includes oral SR dosing and immediate release (IR) ranolazine followed by or combined with SR, including IV IR dosing to a mammal.
The claims also introduce formulation language for an SR product with ranolazine free base and specific pH-dependent binders, plus optional pH-independent binders and typical excipients.
What is the claim-by-claim scope and what does it cover?
A. Primary SR-only “methods of treating” claims tied to specific PK limits
Claim 1
- Indication: “variant and exercise-induced angina” (human)
- Dosage form: SR ranolazine, ≥50% by weight ranolazine
- PK requirement: peak-to-trough plasma ranolazine ratio ≤3:1 over 24 hours
- Frequency: “administered at least once over a 24 hour period”
Claim 2
- Indication: variant and exercise-induced angina (human)
- Dosage form: SR ranolazine, ≥50% by weight
- PK requirement: peak-to-trough ratio ≤4:1 over 24 hours
Claim 3
- Indication: intermittent claudication (human)
- Dosage form: SR ranolazine, PK peak-to-trough ratio ≤4:1 over 24 hours
- Dose frequency: at least once over a 24-hour period
Claim 4
- Indication: myocardial infarction (human)
- Dosage form: SR ranolazine, PK peak-to-trough ratio ≤4:1 over 24 hours
Claim 5
- Indication: cardiovascular disease (human)
- PK language: maintains plasma ranolazine levels “close to minimal effective levels without peak fluctuations” over 24 hours
- Note: this is less numerical than claims 1–4, so it expands coverage to SR products that show controlled exposure rather than a specific ratio.
B. Mammal claims with SR-only and IR-to-SR sequences
These expand beyond the human-only claim set by defining “a mammal,” and by adding IR-to-SR regimens.
Claim 6
- Indication: angina (mammal)
- Dosage form: SR ranolazine with ≥50% by weight
Claim 7
- Indication: cardiovascular disease (mammal)
- Regimen: IR ranolazine followed by or in combination with SR dosage form
- SR composition: SR contains ≥50% by weight ranolazine
Claim 8
- Indication: cardiovascular disease (mammal)
- Regimen: IV IR ranolazine followed by SR dosage form
- SR composition: SR contains ≥50% by weight
Claim 9
- Indication: angina (mammal)
- Regimen: IR ranolazine followed by or in combination with SR
- SR composition: ≥50% by weight
Claim 10
- Indication: angina (mammal)
- Regimen: IV IR ranolazine followed by or in combination with SR
- SR composition: ≥50% by weight
C. Mammal claims that hard-wire a trough threshold
These claims introduce a specific trough level requirement.
Claim 11
- Indication: angina (mammal)
- Regimen: IV IR ranolazine followed by or with SR
- SR PK: maintains trough plasma ranolazine minimum of about 850 ng base/mL over 24 hours
Claim 17
- Indication: arrhythmias (mammal)
- Regimen: IV IR ranolazine followed by SR
- SR PK: maintains trough minimum about 850 ng base/mL over 24 hours
D. Formulation-directed SR claims for composition/pH-binder structure
These claims define an SR dosage form by formulation components rather than only by PK.
Claim 12
- Indication: cardiovascular disease (mammal)
- Dosage form: SR ranolazine dosage form
- Key composition elements:
- ranolazine as free base
- at least one pH-dependent binder
- optional excipients
Claim 13
- Depends on claim 12
- Adds at least one pH-independent binder
Claim 14
- Depends on claim 12 or 13
- Specifies optional excipients can include one or more of:
- fillers
- coloring agents
- flavoring agents
- plasticizers
- film-forming agents
E. Arrhythmia claims (IR-to-SR)
Claim 15
- Indication: arrhythmias (mammal)
- Regimen: IR ranolazine followed by or in combination with SR (≥50% by weight)
Claim 16
- Indication: arrhythmias (mammal)
- Regimen: IV IR ranolazine followed by or in combination with SR (≥50% by weight)
Claim 17
- Indication: arrhythmias (mammal)
- Regimen: IV IR ranolazine followed by SR with the trough ≥850 ng base/mL requirement
How broad is the claim scope by “coverage axis”?
The ’724 patent’s coverage spans at least five overlapping axes:
-
Therapeutic area breadth
- Narrow: variant and exercise-induced angina (claims 1–2)
- Medium: intermittent claudication (claim 3), myocardial infarction (claim 4)
- Broad: cardiovascular disease (claims 5, 7, 8, 12)
- Broadest in cardiology context: arrhythmias (claims 15–17)
-
Species scope
- Human-limited claims: 1–5
- Mammal claims broaden to animals: 6–17
-
Route/regimen scope
- SR-only oral-like scope: claims 1–6, and parts of 12–14
- IR-to-SR sequences: claims 7–10, 11
- IV IR-to-SR: claims 8, 10, 11, 16, 17
-
Exposure control specificity
- Numerical ratio limits: claims 1–4
- Numerical trough threshold: claims 11, 17
- Functional control language: claim 5
-
Composition specificity
- “At least 50% by weight ranolazine” appears in claims 1–4 and 6–10 and 15–16
- “Ranola zine free base + pH-dependent binder” structure appears in claims 12–14
This structure creates multiple entry points for infringement: an accused product could match the PK ratio, the trough, the regimen, or the formulation binder architecture, even if one axis differs.
What are the key limitations that narrow infringement risk?
-
SR dosage form definition tied to ranolazine content
- Claims with “at least 50% by weight ranolazine” constrain what counts as “the dosage form” for those methods (claims 1–4, 6–10, 15–16).
-
PK numeric thresholds
- Peak-to-trough ratio cap:
- ≤3:1 (claim 1)
- ≤4:1 (claims 2–4)
- Trough floor: “about 850 ng base/mL” (claims 11, 17)
- These are objective-looking parameters that can be tested in pharmacokinetic studies.
-
Treatment target is not generic
- Several independent claims tie the method to specific conditions (variant/exercise angina, intermittent claudication, myocardial infarction, arrhythmias).
- Claim 5 and other broader “cardiovascular disease” methods still require clinical alignment with “cardiovascular disease” as construed under claim interpretation.
How does the patent’s claim set interact with commercial ranolazine products?
The ’724 patent targets controlled exposure SR ranolazine with explicit PK consistency. In practice, many SR ranolazine products are designed to produce stable 24-hour exposure and reduce peak/trough swing. The ’724 patent increases enforceability pressure by adding numeric PK thresholds (3:1 and 4:1 ratios) and a trough floor.
The IR-to-SR regimens (including IV IR lead-in) expand the scope beyond a single steady-state SR dosing pattern, capturing combination/sequence dosing approaches that many protocols might employ during initiation or titration.
U.S. Patent Landscape Around U.S. 6,852,724: What to look for
Where are the likely “blocking” and “overlap” areas?
Without compiling the full prosecution history and reference set, the landscape analysis for a drug-device/PK-formulation method patent should focus on these overlap zones:
-
Other ranolazine patents claiming SR ranolazine PK stability
- Look for patents that define SR formulations by:
- peak-to-trough ratio, Cmax/Cmin
- trough levels at steady state
- 24-hour exposure flatness language
- Overlap is most direct with claims 1–5, 11, and 17.
-
Other ranolazine patents claiming high ranolazine loading and SR composition
- The “≥50% by weight ranolazine” element is unusual and can act as a hard differentiator.
- Overlap is most direct with claims 1–4, 6–10, 15–16.
-
Binder/pH-dependent SR release architecture patents
- Claims 12–14 are directed to formulation construction: ranolazine free base + pH-dependent binder, optional pH-independent binder, plus common excipients.
- Overlap likely exists in other patents that disclose SR matrices, binders, and pH-responsive release mechanisms for ranolazine.
-
Dosing initiation/titration sequences
- The IR followed by SR (including IV IR) claims expand beyond “the SR product itself.”
- Overlap likely appears in method patents addressing loading or bridging doses.
-
Indication-driven method claims
- Angina variants, intermittent claudication, myocardial infarction, arrhythmias: each could have parallel method patents for ranolazine with different PK/route constraints.
- Overlap analysis should focus on method patents that tie ranolazine to those conditions while enforcing stable plasma profiles.
What does this mean for freedom-to-operate (FTO) screening of a potential generic or follow-on SR?
An FTO program should categorize potential risk into four bins aligned to the ’724 independent-claim architecture:
| Risk bin |
What triggers potential infringement |
Claims most aligned |
| PK ratio-controlled SR |
Peak-to-trough plasma ratio limits over 24 hours are met in the same direction |
1–4 |
| Trough-floor SR |
Trough floor near 850 ng base/mL over 24 hours |
11, 17 |
| High ranolazine-loading SR |
SR dosage form includes ≥50% by weight ranolazine |
1–4, 6–10, 15–16 |
| IR-to-SR regimen (including IV IR) |
Clinician/administered regimen includes IR followed by or combined with SR, including IV lead-in |
7–10, 11, 15–17 |
| Binder-controlled SR |
Formulation uses ranolazine free base with pH-dependent binder (and optional pH-independent binder) |
12–14 |
If a candidate product misses one bin, it can still hit another. For instance, a product could have different binder chemistry but still be engineered to meet the PK trough/ratio requirements, or could use a different regimen but include IR-to-SR sequences.
What is the “scope leverage” of claim dependencies?
- Claims 13–14 depend on claim 12, so they narrow within a formulation framework built from claim 12’s structural elements.
- Claims 11 and 17 add a numerical trough floor atop the IR-to-SR IV initiation structure.
- The dependent structure increases litigation focus by creating nested alternatives: an infringer does not need to replicate every dependent feature if another independent path matches (for example, claim 15 or 16 may still be implicated without the trough threshold).
Key Takeaways
- U.S. 6,852,724 covers SR ranolazine methods for multiple cardiovascular indications using objective PK stability metrics (Cmax/Cmin peak-to-trough ratios and a trough floor near 850 ng base/mL), plus composition/loading requirements (≥50% by weight ranolazine) and formulation construction (ranolazine free base + pH-dependent binder).
- The claim set is reinforced by alternative infringement pathways: PK ratios (1–4), trough floor (11, 17), high loading SR (1–4, 6–10, 15–16), IR-to-SR dosing sequences including IV IR lead-in (7–10, 11, 16–17), and pH-binder formulation architecture (12–14).
- For landscape and FTO screening, categorize competing ranolazine SR approaches by whether they match: (i) PK ratio limits, (ii) trough threshold, (iii) ranolazine loading, (iv) IR-to-SR regimen structure, or (v) binder/pH-dependent release design.
FAQs
1) Does U.S. 6,852,724 require continuous daily dosing?
No. The claims require the dosage form “administered at least once over a 24 hour period.”
2) Which claims use a numeric peak-to-trough ratio limit?
Claims 1–4. Claim 1 uses ≤3:1; claims 2–4 use ≤4:1.
3) Which claims include a trough threshold of about 850 ng base/mL?
Claims 11 and 17.
4) Do the claims cover formulations without the ≥50% by weight ranolazine limitation?
Yes. Claims 12–14 do not specify the ≥50% by weight loading; they instead focus on ranolazine free base and binder architecture.
5) Are IR-to-SR sequences and IV IR lead-in within the patent scope?
Yes. Claims 7–10, 11, 15–17 cover IR-to-SR sequencing, including IV IR in multiple claims.
References
[1] U.S. Patent 6,852,724.
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