Executive summary
US Drug Patent 10,413,543 claims a specific stable multi-particulate rosuvastatin system: extrusion/spheronized pellets containing rosuvastatin (5 to 30% w/w) plus osmotically driven “release modifiers” (1 to 20% w/w) that cause water imbibition (1 to 20% w/w) followed by disintegration/burst, with stabilizers (1 to 20% w/w), fill/diluent and disintegrant ranges (each 15 to 50% w/w), taste-masked but without a water-insoluble barrier coat, aspect ratio 1 to 2, pellet size distribution constrained by ASTM sieves, capsule/sachet/pouch filling, no drug release when sprinkled on soft food, and rapid release of at least 80% within 10 minutes in 0.01N HCl (pH 1.2) or acetate buffer (pH 4.5). Dependent claims narrow to calcium rosuvastatin, monovalent metal salts as osmotic modifiers (including sodium citrate), and magnesium oxide stabilizer.
The claim set is built to block competitive designs that attempt to (i) replace the core mechanics (extrusion/spheronization + osmotically driven growth/disintegration/burst), (ii) use a conventional water-insoluble barrier taste-coat, (iii) change pellet geometry or size distribution, or (iv) accept slower-than-10-minute dissolution or soft-food “sprinkle” release.
US Patent 10,413,543 rosuvastatin multi-particulate pellets: what do the claims cover and how broad are they?
Core claim-1 architecture is a constraint stack. The independent claim is drafted as a “composite” composition and process-adjacent product claim that requires each of the following to be true simultaneously:
- Morphology and manufacture: pellets are prepared by extrusion and spheronization of a specified rosuvastatin-containing mixture.
- Actives and loading: rosuvastatin (or salts) is the sole active ingredient, at 5 to 30% w/w of the pellet composition.
- Release mechanism: pellets include one or more osmotic release modifiers at 1 to 20% w/w, sufficient to drive pellet growth by water imbibition of 1 to 20% w/w, followed by disintegration or burst.
- Select osmotic modifier list: osmotic modifiers are selected from a defined group including mannitol, sucrose, lactose, fructose, lactitol, sodium citrate, sodium phosphate/sodium bicarbonate, sodium chloride, potassium sulfate, and mixtures.
- Stability excipients: one or more stabilizers selected from defined metal hydroxide/oxide/acetate salts including magnesium hydroxide/oxide/acetate, calcium acetate/gluconate/glycerophosphate, aluminum hydroxide, each at 1 to 20% w/w.
- Diluent and disintegrant ranges: diluent is from a defined list at 15 to 50% w/w, and disintegrant from a defined list at 15 to 50% w/w.
- Taste masking geometry and coating limitation: pellets are surrounded by a taste masking coating but are free of a barrier coating of a water insoluble polymer.
- Pellet geometry: pellet aspect ratio 1 to 2.
- Dosage packaging: filled in capsule, sachet, or pouch.
- Sprinkle-on-soft-food test: when sprinkled on soft food, pellets do not release rosuvastatin/salt.
- Pellet size distribution constraints: pellets free of size >0.8 mm (fails ASTM #20 sieve) and free of size <0.4 mm (passes ASTM #40 sieve).
- Dissolution performance thresholds: in 0.01 N HCl at pH 1.2 or acetate buffer at pH 4.5, the composition releases ≥80% of rosuvastatin within 10 minutes.
Practical implication: even if a competitor matches rosuvastatin, excipient lists, and tablet-like dissolution, it can fall outside claim-1 if it misses any single required constraint. This makes the scope narrower than it looks on paper, even though the enumerated ingredient lists give latitude within those lists.
Which elements of claim 1 are the strongest infringement hooks?
What patents protect the extrusion/spheronization + osmotically driven growth/burst mechanism?
Claim 1 expressly ties product structure to the extrusion and spheronization process and to a mechanistic performance: osmotic modifier causes imbibition-driven pellet growth (1 to 20% by weight water uptake) and then disintegration/burst.
Infringement pressure points for competitors:
- If a competitor uses spray-dried particles, granulation-only methods, or hot-melt multiparticulates without extrusion/spheronization, they can argue noninfringement.
- If they substitute the osmosis/burst concept with pure disintegration (e.g., typical superdisintegrant tablets) without the growth/imbibition requirement, they can also avoid the claim.
What is the significance of “taste masking coating but free of water-insoluble barrier coating”?
Claim 1 mandates: taste masking coating exists, but no water-insoluble polymer barrier coating.
This is an unusual bifurcation that targets a common design route in pediatric/sprinkle formulations. Many taste-masked systems use a water-insoluble polymer barrier (e.g., enteric or insoluble film formers). If a competitor uses an insoluble barrier layer, it can exit claim-1 even if everything else is aligned.
How do pellet aspect ratio and sieve cuts narrow the scope?
Claim 1 fixes:
- Aspect ratio: 1 to 2
- Size window: 0.4 to 0.8 mm (no particles larger than 0.8 mm and none smaller than 0.4 mm)
These parameters can be difficult to “accidentally” hit. If a competitor broadens their pellet size distribution, uses different equipment settings, or targets different spread for food sprinkling, it creates a noninfringement path.
What is the fastest dissolution constraint in claim 1?
The dissolution requirement is unusually strict for a taste-masked multiparticulate:
- In 0.01 N HCl (pH 1.2) or acetate buffer (pH 4.5)
- ≥80% released within 10 minutes
A competitor with slower release kinetics, sustained-release layering, or delayed burst can argue noninfringement.
What is the sprinkle-on-soft-food “no release” hook?
Claim 1 requires that pellets sprinkled on soft food do not release rosuvastatin. This is a behavioral performance constraint tied to dispersibility/coat robustness and burst timing in real food matrices.
This element often drives product testing disputes because it is hard to normalize across food types, pellet loads, and mixing conditions.
How broad are the enumerated excipient lists and what is the real variability?
Osmotic release modifiers (claim 1)
List includes: mannitol, sucrose, lactose, fructose, lactitol, sodium citrate, sodium phosphate + sodium bicarbonate, sodium chloride, potassium sulfate and mixtures.
Key scope insight: the claim covers multiple “osmotic” families, including sugars and salts, so a competitor cannot avoid infringement by swapping among these listed osmotic agents. Avoidance likely requires using an osmotic agent not in the list or changing the growth/imbibition-disintegration profile.
Stabilizers (claim 1)
List includes magnesium hydroxide, magnesium oxide, magnesium acetate, calcium acetate, calcium gluconate, calcium glycerophosphate, aluminum hydroxide.
This list provides some substitution latitude but remains bounded. Competitive formulations using different stabilizers (e.g., different metal salts not listed) can attempt to exit claim-1, but they must still satisfy stability and dissolution.
Diluent and disintegrant lists
Both are constrained to enumerated materials with overlap potential (e.g., low viscosity hydroxypropylcellulose appears in diluent list and also appears in disintegrant list).
The ranges are large (15–50% each), meaning a competitor could still redesign mass balance within those boundaries if other constraints are met.
Dependent claims: what additional limitations do they impose?
Claim 2: rosuvastatin in calcium salt form
Claim 2 narrows claim 1 by specifying rosuvastatin is the calcium salt.
If a competitor uses rosuvastatin calcium or a different salt form (e.g., sodium), claim 2 may not be directly met. Claim 1 still covers rosuvastatin in any pharmaceutically acceptable salt form as long as it is rosuvastatin or its salts and other limitations are met.
Claim 3: osmotic modifier is a salt of a monovalent metal ion
This narrows claim 1’s osmotic modifier category to monovalent metal ion salts.
That typically includes sodium salts more than potassium salts, depending on salt selection, and targets a subset of the claim-1 list.
Claim 4: osmotic modifier is sodium citrate
A single-material narrowing from claim 3.
Claim 5: stabilizer is magnesium oxide
Narrows stabilizer choice from the broader claim 1 group to magnesium oxide.
Scope takeaway: dependent claims are narrower; the independent claim remains the primary risk zone for rosuvastatin multi-particulates meeting the entire composite set of constraints.
What patent estate risk exists for rosuvastatin taste-masked sprinkle multiparticulates in the US?
How claim 1’s structure drives a “design-around” reality
Because claim 1 is a multi-parameter product claim with mechanical, geometric, performance, and coating limitations, competitors typically pursue one or more of these avoidance strategies:
- Replace extrusion/spheronization with a different pellet manufacture process.
- Use taste-masking that includes a water-insoluble polymer barrier layer.
- Move pellet size distribution outside the 0.4–0.8 mm window.
- Alter aspect ratio outside 1–2.
- Achieve taste masking and soft-food stability by a mechanism that also shifts dissolution kinetics so that ≥80% within 10 min is not met in the specified media.
- Use rosuvastatin in a form or formulation variant that changes salt identity (for dependent claim exposure).
Why the claim is less vulnerable to trivial reformulation
The enumerated lists for osmotic modifiers and stabilizers reduce the reformulation playbook: many substitutions remain within the claim’s text.
The real outs are parameter shifts (size/aspect ratio/dissolution time/sprinkle behavior) and coating mechanism (water-insoluble barrier prohibition).
Claim construction map: what would likely be disputed in litigation?
1) “Free of pellets that have a size greater than 0.8 mm / less than 0.4 mm”
Disputes likely center on measurement methodology:
- sieve analysis,
- sampling plan,
- moisture state affecting size,
- lot-to-lot variation.
A valid noninfringement argument can exist if the competitor’s distribution includes any out-of-window population.
2) “Taste masking coating but free of a barrier coating of a water insoluble polymer”
Key disputes:
- Whether the coating includes an insoluble barrier polymer layer,
- Whether a particular polymer qualifies as “water insoluble,”
- How coating layers are classified (taste masking vs barrier).
3) “Pellets when sprinkled on soft food do not release rosuvastatin”
This performance clause drives disputes over:
- what qualifies as “soft food,”
- pellet quantity and mixing,
- time-to-observation,
- acceptable detection limits.
4) Dissolution: “≥80% within 10 minutes” at pH 1.2 and pH 4.5
Disputes often arise over:
- apparatus settings,
- sampling times and normalization,
- sink conditions,
- whether the measured entity is “released rosuvastatin” vs assay carryover.
Which product archetypes are most at risk of overlapping this claim?
Most at risk
- US products that are rosuvastatin sprinkles or “openable” multiparticulates with taste masking and rapid release in both gastric and weakly acidic buffer.
- Products that avoid enteric/insoluble barrier polymers but still use a taste-masking coat.
- Any generic/bioequivalent that uses extrusion/spheronization pellets with osmotically active bulking/disintegration agents and a tight pellet size window.
Lower at risk
- Enteric-coated systems designed for delayed release beyond 10 minutes in pH 1.2 or pH 4.5.
- Systems using water-insoluble barrier coatings as a primary taste-masking approach.
- Non-spheronized multiparticulates that are not “pellets prepared by extrusion and spheronization.”
Timeline and exclusivity: what does this patent likely protect over time?
The user request provides claim text but not filing/publication data. Without those, any exclusivity timeline or expiration date would be unsupported. Accordingly, no dates are provided.
Orange Book and FDA listing status: what is the regulatory tie to claim scope?
The user request provides the patent number and claims but not the tied product, NDA/BLA, Orange Book listings, or FDA reference. Without that mapping, no Orange Book analysis is produced.
Key Takeaways
- US 10,413,543 claim 1 is a tightly constrained composite claim for extrusion/spheronized osmotically driven rosuvastatin pellets with: specific excipient lists and ranges, no water-insoluble barrier polymer in the taste-masking system, fixed aspect ratio (1 to 2), pellet size window (0.4 to 0.8 mm), and rapid dissolution (≥80% in 10 min) in both pH 1.2 HCl and pH 4.5 acetate buffer, plus no release on soft food sprinkling.
- Dependent claims narrow to rosuvastatin calcium, monovalent metal salt osmotic modifiers (including sodium citrate), and magnesium oxide stabilizer.
- From a freedom-to-operate standpoint, likely design-around routes are: changing pellet manufacture, adding an insoluble barrier layer, shifting pellet geometry/size distribution, shifting dissolution kinetics outside the 10-minute/≥80% threshold, or using osmotic and stability systems that fall outside the claim’s enumerated structures.
FAQs
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Can a rosuvastatin sprinkle product avoid US 10,413,543 by using a different pellet size distribution?
If any pellets fall outside the claim-1 sieve constraints, the product can fall outside claim scope for that parameter.
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Does using a water-insoluble taste-masking barrier polymer automatically avoid claim 1?
Claim 1 requires the pellets be “free of a barrier coating of a water insoluble polymer,” so inclusion of such a layer is a direct textual avoidance route.
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If a product uses sodium citrate, does it automatically infringe?
Not automatically. Claim 1 also requires the extrusion/spheronization, specific excipient ranges, aspect ratio, size window, sprinkle behavior, and dissolution threshold.
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Is the 10-minute “≥80% release” requirement the main performance risk?
It is a major performance constraint because it is explicitly time- and media-specific, narrowing products with slower or pH-shifted release.
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Do dependent claims (calcium salt, sodium citrate, magnesium oxide) matter if a product meets claim 1?
Yes for specific-formulation infringement, but claim-1 coverage remains the primary scope risk when all independent limitations are met.
References (APA)
- United States Patent 10,413,543. (Claim text provided by user).
