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Patent landscape, scope, and claims: |
United States Patent 6,372,252 (Guaifenesin Modified-Release Bilayer Tablet): Scope, Claim-by-Claim Coverage, and U.S. Patent Landscape
What is U.S. Patent 6,372,252 claiming for guaifenesin modified-release tablets?
U.S. Patent 6,372,252 claims a specific guaifenesin modified-release oral dose form with two functional portions (immediate + sustained) engineered to match a defined pharmacokinetic (PK) target: an early Cmax equivalent to a defined three-dose schedule of a standard immediate-release (IR) comparator and sustained therapeutic bioavailability for at least 12 hours post-dose. The sustained portion uses a controlled-release matrix defined by a hydrophilic polymer : water-insoluble polymer weight ratio (about 1:1 to 6.8:1) and further dependent claims specify preferred polymer types, compositional ranges, and tablet/capsule geometries.
At a high level, the estate is not “any guaifenesin ER.” It is “guaifenesin ER” constrained by:
- Dose architecture: two portions, with the first portion being immediate release that “becomes fully bioavailable in the subject’s stomach,” and the second portion being sustained release.
- PK performance: Cmax equivalence to a comparator IR regimen and exposure persistence for ≥12 hours, measured by serum analysis.
- Release-matrix composition: a defined hydrophilic/ininsoluble polymer ratio and, in dependent claims, preferred polymer families and an example composition.
- Form factor: bilayer tablets, coated configurations, and capsule containing two portions.
- Optional but claim-driving quantitative endpoints: dosage strengths (600 mg and 1200 mg) and corresponding Cmax/AUC ranges.
How broad is claim scope: “drug product” vs “matrix” vs “PK method”?
The independent claim (claim 1) is a product claim directed to “a modified release tablet having two portions,” but it includes functional and PK performance limitations, which often narrow enforceability to accused products that meet those PK targets under comparable test conditions.
Claim architecture that narrows scope
- The sustained portion is constrained by matrix polymer pairing defined by hydrophilic polymer family + water-insoluble polymer family and a ratio window (1:1 to 6.8:1).
- The claim includes a Cmax equivalence standard tied to a “standard IR formulation” dosing schedule (first of three doses, one third strength, every 4 hours over 12 hours).
- It also requires therapeutically effective bioavailability for at least 12 hours after a single dose “according to serum analysis.”
Claim architecture that expands scope
- The polymer lists are broad (multiple hydrophilic polymer options; multiple water-insoluble polymer options).
- The geometry/form factor includes bilayer tablets and coated tablets and even capsules containing first and second portions (claims 38 and 54).
- Multiple dependent claims carve out dosage strengths and PK ranges, but the independent claim already covers performance.
What do the independent claims cover?
The claim set you provided includes multiple independent-style groupings: claim 1 and then claim 24 and claim 41 (product claims with similar constraints). All three are structured around the same core invention: two portions (IR + sustained) with PK targets and polymer ratio constraints.
Claim 1 (tablet; two portions; polymer ratio 1:1 to 6.8:1)
Core limitations
- Two portions:
- Portion 1: IR guaifenesin fully bioavailable in the stomach.
- Portion 2: sustained release guaifenesin with a matrix comprising hydrophilic polymer + water-insoluble polymer.
- Matrix ratio: hydrophilic : water-insoluble = ~1:1 to ~6.8:1.
- PK performance:
- Cmax equivalent to Cmax obtained when the first of three doses of a standard IR formulation (with one third the amount of guaifenesin) is dosed every four hours over a 12-hour period.
- Therapeutically effective bioavailability for ≥12 hours after a single dose, by serum analysis.
Practical scope implication
- Any accused product must be a modified-release tablet meeting both the polymer ratio window and the PK comparator-based Cmax requirement.
Claim 24 (modified release product; two portions; ratio-driven Cmax equivalence)
Claim 24 is broader in format language (“modified release product”) than claim 1, but retains:
- Two portions (IR first portion, sustained second portion).
- Ratio of first quantity to second quantity that provides Cmax equivalence to the same comparator IR regimen.
- ≥12 hours therapeutically effective bioavailability.
- Dependent claims specify total dose 600 mg/1200 mg, bilayer tablet, coated, etc. (claims 25-27, 36-37, 38, 39).
Claim 41 (modified release product; tighter matrix ratio range via first:second quantity)
Claim 41 includes:
- First portion IR, second portion sustained.
- Ratio of first quantity to second quantity 1:1 to 1:5 (claim-specific to this independent-like set).
- Same comparator Cmax equivalence concept.
- Same ≥12 hours bioavailability.
Scope implication
- Claim 41 ties the partition between IR and sustained portions to the PK outcome.
Which polymer selections and ratio controls define the sustained-release matrix?
What hydrophilic polymer options are claimed? (dependent claims 2, 4)
Claim 2 lists hydrophilic polymers including:
- polysaccharides and gums: acacia, gum tragacanth, locust bean gum, guar gum, karaya gum
- modified and substituted cellulosics: methylcellulose, hydroxyethylcellulose, hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose, carboxymethylcellulose, agar, pectin, carrageen, alginate
- other hydrophilic matrix formers: gelatin, casein, zein, bentonite, magnesium aluminum silicate
- modified starch derivatives and other broad descriptors: polysaccharide, modified starch derivatives, and “combination thereof.”
Claim 4 narrows to a specific pair:
- hydrophilic polymer = hydroxypropyl methylcellulose
- water-insoluble polymer = an acrylic resin.
What water-insoluble polymer options are claimed? (dependent claim 3)
Claim 3 lists water-insoluble polymers including:
- polyacrylic acids
- acrylic resins and acrylic latex dispersions
- cellulose acetate phthalate
- polyvinyl acetate phthalate
- hydroxypropyl methylcellulose phthalate
- combinations.
How is the matrix ratio constrained?
- Independent claim 1: hydrophilic : water-insoluble polymer weight ratio about 1:1 to 6.8:1.
- Dependent claim 18 provides a concrete example composition for the second portion:
- about 95.5% guaifenesin DC
- about 2.4% hydrophilic polymer
- about 1.2% water-insoluble polymer
(This numerically implies a ratio near ~2:1, consistent with the broader window.)
How do claims 23 and 18 relate?
Claim 23 specifies ranges for second portion composition:
- 85.5% to 91.4% guaifenesin
- 6.8% to 10.1% hydrophilic polymer
- 1.1% to 2.9% acrylic resin
This is the tighter “composition window” dependent upon claim 9 (the 600 mg example in your extract).
What PK endpoints and comparator logic narrow enforceability?
What does “Cmax equivalence” mean in claim 1?
Claim 1 requires that the modified-release tablet demonstrates a Cmax in a human subject equivalent to the Cmax obtained when the first of three doses of a standard IR formulation (one third the amount) is dosed every four hours over 12 hours.
That is a defined clinical PK target with an explicit comparator schedule. Under infringement, the plaintiff typically uses PK study data and test conditions aligned to the reference.
What does “therapeutically effective bioavailability for at least twelve hours” require?
It is functional and measured by serum analysis. It is a performance claim tied to exposure duration.
Are there numeric PK ranges in dependent claims?
Yes. For the 600 mg and 1200 mg strengths, dependent claims specify Cmax and AUCinf windows.
For 600 mg (claim 8, then dependent 15-16; also claim 49)
- Cmax about 800 to 1250 μg/mL and *AUCinf about 2800 to 4375 hrμg/mL** (claim 15)
- Alternatively: Cmax ≥1000 μg/mL and *AUCinf ≥3500 hrμg/mL** (claim 16)
- claim 49 repeats a similar structure under the “modified release product” lineage.
For 1200 mg (claim 9, then dependent 13-14; also claim 47-48)
- Cmax about 1600 to 2500 μg/mL and *AUCinf about 5600 to 8750 hrμg/mL** (claim 13)
- Alternatively: Cmax ≥1900 μg/mL and *AUCinf ≥7000 hrμg/mL** (claim 14)
- claim 48 repeats the higher-threshold structure.
Does the patent assume dose proportionality?
Yes:
- claim 10: Cmax, AUCinf and AUC0-12 approximately proportional to dosage strength
- mirrored in claim 28 and claim 45.
This can matter for infringement where accused products are near the same mg strength but have different PK nonlinearity profiles.
How much of the claim scope is about formulation geometry?
What bilayer configurations are claimed?
- Claim 19: first and second portions are “abutting substantially planar layers” forming a bilayer tablet.
- Claim 36 mirrors this for product versioning.
How is coating covered?
- Claim 20: first portion provided as a coating on second portion.
- Claim 37 mirrors this.
How is capsule containment covered?
- Claim 38: product is a capsule containing first and second portions.
- Claim 54 mirrors this.
Practical scope implication
Even if an accused product is not a classic bilayer tablet, a coated or capsule-contained architecture can still fall within dependent claim coverage, depending on whether it still meets the polymer ratio and PK targets.
What quantitative dosing partition is claimed?
First IR portion vs second sustained portion ratio
- claim 11: first quantity : second quantity about 1:1 to 1:5
- claim 12: specifically about 1:5
- claim 41: in the independent-like set, ratio is about 1:1 to 1:5
- claim 46: specifically 1:5
These claims constrain the proportioning that drives the PK Cmax equivalence.
What does “equal effectiveness on empty vs full stomach” cover?
- claim 21: tablet approximately equally effective on empty or full stomach.
- claim 39: mirrored for product versioning.
- claim language suggests GI condition robustness, potentially tightening infringement if the accused product shows a food effect different from the claimed behavior.
How does this patent map to likely competitive design-arounds?
Given the combination of polymer ratio constraints + PK equivalence to an IR comparator schedule, common design-around routes generally include:
- changing the hydrophilic:insoluble polymer ratio outside 1:1 to 6.8:1
- using polymer families outside the listed groups (though doctrine-of-equivalents risk exists depending on interpretation)
- altering dose partition (first:second quantity) so the Cmax equivalence target is not met
- changing release timing so that the sustained portion does not deliver “≥12 hours therapeutically effective bioavailability” per serum analysis.
Because the claims you provided are not limited to a single manufacturing method, design-arounds are primarily formulation and performance.
What is the U.S. patent landscape around this invention?
A precise “patent landscape” (other U.S. patents, filing families, expiration dates, and Orange Book relevance) cannot be completed from the claim text alone. The patent landscape is driven by:
- bibliographic data (assignee, priority dates),
- citation network (related patents referencing the same guaifenesin ER split-dosing and matrix polymers),
- and FDA product listing (Orange Book) for the specific guaifenesin ER/NDC product(s).
Since the request is for detailed landscape and scope of this specific patent number, the only accurate deliverable requires the missing bibliographic and Orange Book context.
What can be stated confidently from the claims themselves (scope inventory)
Covered product types (within claim set)
- Modified-release tablet with two portions (claim 1)
- Modified-release product with two portions (claims 24, 41) covering:
- bilayer tablet (claims 36, 52)
- coated first portion on second (claims 37, 53)
- capsule containing first and second portions (claims 38, 54)
Covered strengths and PK bands (within your extract)
- 600 mg strength: Cmax and AUCinf bands (claims 15-16, and mirrored in claims 49-50)
- 1200 mg strength: Cmax and AUCinf bands (claims 13-14, and mirrored in claims 47-48)
- Dose proportionality: Cmax/AUCinf/AUC0-12 approximately proportional (claims 10, 28, 45)
Covered polymer matrix families
- hydrophilic polymers: broad list including HPMC
- water-insoluble polymers: broad list including acrylic resins
- ratio: hydrophilic:water-insoluble about 1:1 to 6.8:1 (claim 1)
- example composition in second portion: claim 18 (quantitative)
- example compositional ranges: claim 23 (quantitative; tied to 600 mg claim lineage)
Claim-by-claim scope notes that matter for infringement analysis
Claims 1/24/41: the core infringement hook
Any accused product must satisfy:
- IR portion fully bioavailable in stomach
- sustained portion with matrix polymer pair and ratio (claim 1) or with partition ratio (claims 24/41)
- PK Cmax equivalence comparator
- ≥12 hour therapeutic bioavailability by serum analysis
Claims 2-4 and 3: polymer identity substitutions
- If accused product uses HPMC + acrylic resin, it lands squarely in claim 4.
- If polymer choices stay within the listed families, claim 2 and 3 keep coverage broad.
Claims 7-9 and 13-16: dosage-strength-specific PK windows
- Accused products at 600 mg or 1200 mg must hit the claimed Cmax/AUCinf ranges in the relevant dependent claims to fall cleanly within those dependent claim scopes.
- Even if the independent claims apply, these dependent claims offer structured PK targets that can be used in litigation to show equivalence or non-equivalence.
Claims 11-12 / 29-30 / 41 / 46: partition ratio is a control lever
- Changing the fraction of IR guaifenesin vs sustained guaifenesin can shift Cmax timing and amplitude, potentially moving the product away from comparator equivalence.
Claims 19-21 / 36-39 / 52-55: physical and food-effect constraints
- Bilayer vs coating vs capsule containment affects whether dependent claims apply.
- Food-effect “approximately equally effective” can narrow where accused products have meaningful fed-batch effects.
Key Takeaways
- U.S. Patent 6,372,252 is a guaifenesin ER two-portion product patent constrained by PK performance (Cmax equivalence to a defined IR comparator regimen and ≥12-hour therapeutic bioavailability) and a defined hydrophilic/ininsoluble polymer matrix ratio (about 1:1 to 6.8:1).
- The strongest scope anchor is the combination of (i) two-part release architecture, (ii) specific polymer pairing/ratio, and (iii) PK equivalence and duration limits. Those are the features most likely to distinguish infringement from non-infringement.
- Dependent claims materially narrow into polymer identities (e.g., HPMC + acrylic resin), composition ranges for the sustained portion, dose strengths (600 mg and 1200 mg) with specific Cmax/AUCinf bands, and form factor (bilayer, coated, capsule containment) plus food-effect behavior.
FAQs
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Does U.S. Patent 6,372,252 cover guaifenesin ER capsules if they contain immediate-release and sustained-release portions?
Yes, through dependent claims that explicitly cover “a capsule containing said first and second portions.”
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What is the critical matrix ratio range in the patent?
About 1:1 to about 6.8:1 hydrophilic polymer to water-insoluble polymer (claim 1).
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Which hydrophilic polymer and water-insoluble polymer pairing is explicitly called out?
Hydroxypropyl methylcellulose (hydrophilic) with an acrylic resin (water-insoluble) (claim 4).
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What are the claimed PK numeric windows for the 600 mg and 1200 mg strengths (in your extract)?
For 600 mg: Cmax ~800-1250 μg/mL and AUCinf ~2800-4375 hrμg/mL; for 1200 mg: Cmax ~1600-2500 μg/mL and AUCinf ~5600-8750 hrμg/mL (claims 13-16, and mirrored in the product claims).
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How does the patent handle fed vs fasted dosing?
It claims “approximately equally effective” performance on empty or full stomach (claims 21 and 39, and their lineage mirrors).
References
- U.S. Patent 6,372,252.
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