United States Patent 6,696,084 (Fenofibrate Microparticles With Phospholipid Surface Stabilization): Scope, Claim Architecture, and Landscape
Summary
US 6,696,084 claims a solvent-free, high-shear + high-pressure homogenization + spray-drying manufacturing route to make fenofibrate small particles/microparticles with a phospholipid surface stabilizing substance, optionally using bulking agents (saccharides/polyols) and controlled water content. It also claims pharmaceutical dosage forms (including fasted vs fed exposure parity targets using AUC/relative systemic exposure windows) and optional statin co-loading/combination. The claims are layered from broad process features (Claim 1) into narrower parameter gates (temperature, pressure, particle size, water %, excipient/phospholipid identity), then into pharmacokinetic performance constraints (Claims 15-20, 36-38, 47), and finally into combination extensions (Claims 49-60).
What is the core invention protected by Claim 1?
Independent Claim 1 is the anchor. It defines a manufacturing process with a tight combination of:
- No organic solvent
- High shear mixing of fenofibrate + phospholipid in aqueous carrier
- Temperature control at/above fenofibrate melting point
- High-pressure homogenization in the same temperature window
- Spray drying to form dried microparticles
- Bulking agent added at either step (a) or (b)
- Phospholipid is a required surface active agent
Claim 1: structural elements (requirement stacking)
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Step (a): high shear mixing
- Mixing at high shear an admixture of:
- fenofibrate
- phospholipid (phospholipid is also “at least one surface active agent”)
- aqueous carrier
- Absence of an organic solvent
- Optionally one or more additional surface active substances
- Temperature range at or above the melting point of fenofibrate
- Results in heated suspension
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Step (b): pressure homogenization
- Homogenize heated suspension
- Pressure range and within same temperature range
- Results in heated homogenate
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Step (c): spray drying
- Spray dry heated homogenate
- Produces dried small particles containing fenofibrate
- One or more bulking agents added at any stage of step (a) or (b)
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Composition function constraint
- Microparticles have a phospholipid surface stabilizing substance
This combination is not a simple “lipid coating” claim. It is a process-defined solid state + surface-stabilization structure: the product is what the process is engineered to deliver.
What are the claim categories and how do they narrow scope?
1) Process claims (manufacturing route + critical parameters)
Besides Claim 1, the claim set uses dependent claims to lock down:
- Bulking agent identity (Claims 2-3)
- Phospholipid identity (Claims 4-5)
- Temperature window (Claim 6)
- Aqueous carrier selection + pH (Claims 7-9)
- Pressure range (Claim 10)
- Particle size ranges (Claims 11-13 and multiple “max size” claims 29-33)
- Phospholipid loading range (Claims 41-42)
- Water content (Claims 43-46) including “0.1 to about 5% water” (Claim 34)
- Optional addition of statin during homogenate creation (Claims 49-50)
2) Composition claims (product defined by process)
- Claim 14: composition comprising microparticles containing fenofibrate + phospholipid surface stabilizer, prepared per Claim 1, with 0.1 to about 5% water
- Claims 15-20: dosage forms using process-prepared microparticles but bounded by fasted vs fed exposure performance thresholds.
- Claims 34-35: repeat the water content and fenofibrate dose listing.
3) Product-by-parameters + pharmacokinetic performance claims
Claims 15-20 and 36-38 define performance gates like:
- fasted systemic exposure as % of fed exposure.
- multiple tight thresholds: >90%, >85%, >95%, >90% (again), >97/98 not shown, but explicitly:
- Claim 15: greater than 90% fed comparison
- Claim 16-20: fasted differs by less than 25%, 20%, 15%, 10%, 5%
- Claim 36-38:
- Claim 36: fasted provides >85% of fed when fed ≥1000 calories with 50% fat
- Claim 37: fasted provides >90% of fed under same feeding condition
- Claim 38: fasted provides >95% of fed under same feeding condition
Claim 47 restates a AUC-based criterion:
- fasted AUC ≥ 90% of fed AUC
4) Combination-extension claims (statin + fenofibrate co-formulation)
Claims 49-60 extend the process and product to include a statin added to the heated homogenate and recite:
- statin identity list (Claims 50, 52, 54, 56, 58, 60)
- in process + composition + dosage + method forms (Claims 49-60)
5) Formulation sub-claims (tablet coating and excipient selection)
Multiple dependent claims specify:
- dried film-coating formed by water based solution (Claim 21)
- pharmaceutically acceptable polymer in a coating (Claim 22)
- pharmaceutically acceptable carbohydrate in coating as sugar (Claims 23-24)
- excipients list (Claim 25)
- phospholipid mixture or specific phospholipids (Claims 26-27)
- crystalline fenofibrate (Claim 28)
What is the explicit scope of Claim 2-3: bulking agents?
Claim 2: bulking agent from broad sugar/polyol classes:
- monosaccharides/disaccharides/trisaccharides (generic categories)
- lactose, mannitol, sorbitol, trehalose, glycerol, dextrose, fructose, xylitol
- mixtures
Claim 3: narrower subset:
- sucrose, lactose, mannitol, sorbitol, trehalose (plus mixtures)
Claim 25 (dosage form excipients) repeats the broad carbohydrate/polyol set including:
- monosaccharides, disaccharides, trisaccharides, raffinose, lactose, mannitol, sorbitol, trehalose, glycerol, dextrose, maltodextrose, fructose, xylitol.
Landscape implication: the claim set allocates separate coverage for (i) bulking agent added during manufacturing and (ii) downstream excipient selection in the dosage form, which can matter for design-around (where a competitor may avoid certain bulking agents but still use other excipients).
What is the explicit scope of Claim 4-5: phospholipid types?
Claim 4: phospholipid surface active agent list:
- Lipoid E80
- Lipoid EPC
- Lipoid SPC
- DMPG
- Phospholipon 100H
- Lipoid SPC-3
- Phospholipid class alternatives not listed are limited by the claim’s dependency; Claim 1 already requires “phospholipid” but Claim 4 narrows to named exemplars.
Claim 5: specifically Lipoid E80.
Claim 27 and Claim 40 repeat similar phospholipid lists in dosage-form territory, including:
- egg phospholipid
- Lipoid E80 / EPC / SPC
- DMPG
- Phospholipon 100H (spelling in text “Phospholipon 100H”)
- hydrogenated soybean phosphatidylcholine
- Phospholipon 90H
- Lipoid SPC-3
Claim 26: phospholipid surface stabilizing substance comprises mixture of phospholipids.
What are the explicit manufacturing parameter gates (temperature, pressure, water, size, pH)?
Temperature
Claim 6:
- temperature range = from melting point of fenofibrate to 20°C above fenofibrate melting point
This is unusually specific because it limits how far above melt competitors can operate.
Aqueous carrier and pH
Claim 7:
- aqueous carrier: water or buffered water
- buffer pH from 4 to 10
Claim 8:
- phosphate buffered water, pH 7 to 9
Claim 9:
- phosphate buffered water, pH 7.5 to 8.5
Pressure
Claim 10:
- homogenization pressure range 2,000 to 30,000 psi
This is a meaningful design constraint because the claim ties spray drying product outcome to high-pressure homogenization conditions.
Particle size
Claim 11-13:
- average size 0.1 to 10 µm
- average size 0.1 to 5 µm
- average size 0.1 to 2 µm
Claims 29-33 are “less than” thresholds applied to the dosage form tied to Claim 16:
- <5 µm
- <4 µm
- <3 µm
- <2 µm
- <1 µm
These create a gradient of narrower infringement positions if a competitor targets different PSD outcomes.
Phospholipid content
Claim 41: phospholipid present about 0.1% to 15%
Claim 42: phospholipid present about 0.5% to 5%
Water content (post-drying residual)
Claim 14: composition has 0.1 to about 5% water
Claims 34-46 provide narrower ranges:
- Claim 34: 0.1 to about 5%
- Claim 43: 0.1 to 5%
- Claim 44: 0.1 to 3%
- Claim 45: 0.1 to 2%
- Claim 46: 0.1 to 1%
Landscape implication: moisture/residual water is often a stability lever. The claim set grants enforcement hooks if competing product manufacturing leaves different residual water.
What is the explicit pharmacokinetic (fasted vs fed) scope?
This patent’s enforcement value is not only about micronized/phospholipid particles. It uses performance-based product claims.
Fasted vs fed comparisons
Claim 15:
- fasted active species provided by the oral pharmaceutical composition is >90% of fed under a high-fat meal context (text: “fed a high fat meal”)
Claims 16-20:
- fasted differs by less than:
- 25% (Claim 16)
- 20% (Claim 17)
- 15% (Claim 18)
- 10% (Claim 19)
- 5% (Claim 20)
The text describes a blood level comparison between fasted and fed states.
Claims 36-38:
- fed challenge: at least 1000 calories with 50% fat
- fasted active species is >85% (Claim 36), >90% (Claim 37), >95% (Claim 38)
Claim 47 (method claim):
- provides into blood of patient in fasted state:
- at least 90% of the AUC amount compared to fed
Landscape implication: performance thresholds can narrow the practical infringement surface. A competitor can use a similar manufacturing approach but show lower fasted exposure vs fed; this can matter for non-infringing equivalents where claim language is strict.
How far does the combination scope extend to statins?
Process extension:
- Claim 49: heated homogenate further comprises a statin added thereto
- Claim 50: statin is selected from:
- lovastatin, pravastatin, simvastatin, atorvastatin, rosuvastatin, fluvastatin, itavastatin, cerivastatin
Product and dosage extensions:
- Claim 51: composition prepared per Claim 1 further containing a statin
- Claim 53-58: oral pharmaceutical composition with statin and listed identity
- Claim 59-60: method of treating dyslipidemia with statin present
Practical coverage: the statin insertion is constrained to “heated homogenate” context (process side) but then carried through into the prepared microparticles and final dosage forms.
What conditions define the medical use scope?
Claim 47: treatment method for a mammal by administering once daily:
- dyslipidemia and dyslipoproteinemia
- using the process-prepared microparticles dosage form
- with AUC-based parity (fasted ≥90% fed)
Claim 48 defines dyslipidemia components:
- hypercholesterolemia
- hyperlipidemia
- hypertriglyceridemia (spelling “hypertrigylceridaemia” in text)
- combinations
Dosage form frequency is fixed in Claim 47: once a day.
What are the dosage form formulation hooks?
The claims include specific tablet coating/excipient elements tied to Claim 16:
- Film coating: water based solution (Claim 21)
- Coating polymer: pharmaceutically acceptable polymer (Claim 22)
- Coating carbohydrate: pharmaceutically acceptable carbohydrate (Claim 23)
- sugar as carbohydrate (Claim 24)
- Excipient set (Claim 25): includes monosaccharides/disaccharides/trisaccharides and specific polyols like mannitol/sorbitol/trehalose plus lactose and maltodextrose.
- Phospholipid surface stabilizing substance in dosage form (Claims 26-27)
- Fenofibrate crystalline (Claim 28)
- Dose listing (Claim 35): enumerates fenofibrate amounts (e.g., 50 mg, 51 mg, 52 mg, … up to 300 mg)
Patent landscape: how US 6,696,084 is likely positioned relative to adjacent fenofibrate delivery patents
Given only the claim text provided here, the only rigorous landscape statements that can be made are claim-driven: where this patent sits in the design space and where it creates blocking coverage.
Landscape positioning (claim-driven)
US 6,696,084 occupies a niche defined by:
- fenofibrate
- phospholipid surface stabilization
- solvent-free aqueous route
- high shear + high pressure homogenization
- spray drying
- small particle sizes (down to <1-2 µm variants via dependent claims)
- residual water defined
- pharmacokinetic parity targets between fasted and fed states
- optional statin co-formulation
Design-around levers that the claim set exposes
Because the claims stack process and performance gates, common design-around strategies would include:
- changing the stabilization agent away from the defined phospholipid requirement (but Claim 1 requires “at least one surface active agent is a phospholipid,” so removing phospholipid removes the basis)
- using an organic solvent in manufacturing (Claim 1 requires absence of organic solvent)
- moving outside the defined temperature window (from melting point of fenofibrate to +20°C)
- moving outside pressure 2,000 to 30,000 psi
- targeting a different residual water band
- failing pharmacokinetic parity targets (fasted/fed exposure difference thresholds)
- avoiding the bulking agent classes listed if the competitor wants to avoid dependent claim coverage, though Claim 1 already allows “one or more bulking agents” without limiting identity unless dependent claims 2-3 are invoked.
Enforcement leverage points
The strongest practical enforcement positions are:
- Claim 1 process plus dependent phospholipid/bulking/temperature/pressure/particle size gates.
- Claims 15-20 and 36-38 if performance tests map to the same measurement definitions (fasted vs fed, with high-fat meal criteria).
- Claim 47 AUC ≥90% if the clinical protocol used by competitors yields lower parity.
Key Takeaways
- US 6,696,084 is anchored on a solvent-free aqueous manufacturing process using high shear mixing, high-pressure homogenization (2,000 to 30,000 psi), and spray drying to produce fenofibrate microparticles stabilized by a phospholipid surface active substance.
- The claim set narrows scope through temperature (fenofibrate mp to +20°C), aqueous buffer pH (notably 7-9 or 7.5-8.5 for phosphate), particle size ranges (down to 0.1 to 2 µm and also less than 1-5 µm variants), phospholipid loading (0.1-15% and 0.5-5% variants), and residual water (0.1% to 5% and narrower bands down to 0.1-1%).
- The patent’s commercial moat is the addition of fasted vs fed pharmacokinetic performance targets: fasted systemic exposure must be close to fed (greater than 85%/90%/95% in the high-fat challenge, or “less than 25% to 5%” differences in blood levels, plus AUC ≥ 90% in the method claim).
- The landscape extension includes statin co-formulation, with the statin list specified and statin addition recited at the heated homogenate stage.
FAQs
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What does US 6,696,084 most strongly protect: a formulation or a process?
It protects a process (Claim 1) that yields fenofibrate microparticles with phospholipid surface stabilization, and then extends to dosage forms defined by that process and by fasted vs fed exposure targets.
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What are the key “must-hit” manufacturing constraints for Claim 1?
No organic solvent, aqueous carrier, high shear at/above fenofibrate melting point, high-pressure homogenization, and spray drying, with phospholipid as surface active agent and bulking agent added during step (a) or (b).
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Which parameters are explicitly bounded to ranges in dependent claims?
Temperature: mp to +20°C; pressure: 2,000 to 30,000 psi; pH: 4-10 and phosphate 7-9 / 7.5-8.5; particle size: 0.1-10 µm down to 0.1-2 µm plus maximum variants; phospholipid: 0.1-15% and 0.5-5%; water: 0.1-5% down to 0.1-1%.
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How does the patent define pharmacokinetic performance?
It uses fasted vs fed systemic exposure parity: e.g., fasted active species >90% of fed, or “differs by less than” 25%/20%/15%/10%/5%, and also an AUC condition in Claim 47 (fasted AUC at least 90% of fed).
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Does it cover co-formulation with statins?
Yes. Dependent claims add a statin to the heated homogenate and then claim corresponding compositions, dosage forms, and methods, with a specified statin list.
References
- US Patent 6,696,084, “Process for the preparation of fenofibrate microparticles with phospholipid surface stabilizing substance,” claim text as provided by user.
