United States Patent 6,955,821 (Guaifenesin Modified-Release + Hydrophilic/Water-Insoluble Matrix): Claim Scope, Coverage Map, and US Patent Estate Risk
Executive summary: US Drug Patent 6,955,821 claims a guaifenesin modified-release oral drug product that combines (1) an immediate-release guaifenesin fraction that becomes bioavailable in the stomach with defined serum Cmax timing and exposure constraints, and (2) a release-delaying or sustained-release fraction made with a hydrophilic polymer + water-insoluble polymer in a hydrophilic:insoluble weight ratio of ~1:1 to ~9:1, with optional combination actives (notably dextromethorphan and pseudoephedrine) and tightly defined dose ratios. The strongest enforcement posture is for specific pharmacokinetic (PK) profiles (Cmax within equivalency to an IR comparator at one-third dose, Tmax ~1 hour, and a 12-hour “no-drop-below” constraint) plus the polymer pair and ratio. Risk to generics is driven by the claim’s functional serum PK limitations and its polymer composition/range that constrain design-around attempts.
What patents protect guaifenesin modified-release oral products with hydrophilic and water-insoluble polymers?
Core protection in US 6,955,821 is product composition + PK performance + optional combination actives. The independent product claims you provided are claim 1, claim 29, and claim 43, all built around the same technical center of gravity:
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Two guaifenesin fractions in one dosage form:
- A first quantity in an immediate-release formulation that becomes bioavailable in the stomach
- A second quantity in a release-delaying matrix (claims 1, 70) or sustained release form (claims 29, 43)
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Polymer system for the delayed/sustained fraction:
- Hydrophilic polymer + water-insoluble polymer
- Weight ratio hydrophilic:water-insoluble from about 1:1 to about 9:1 (independent claims)
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PK-limited “equivalence to a comparator” constraints:
- Immediate-release guaifenesin has Cmax equivalent to the Cmax from an IR comparator dose = one-third the amount of guaifenesin
- Serum concentration peaks ~1 hour
- Concentration decreases over 24 hours but never decreases below the minimum concentration of the comparator over 12 hours
- Single dose must provide therapeutically effective bioavailable guaifenesin dose for at least 12 hours based on serum analysis
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Optional co-therapy:
- At least one additional drug is permitted and claim 6 narrows the class to antitussive, decongestant, antihistamine, analgesic, or combinations
- Claim 7 and 8 enumerate extensive candidate actives, with specific coverage for dextromethorphan and pseudoephedrine combinations
How many independent claim “families” exist inside 6,955,821 based on your text?
From the excerpted claim set, the independent structures are essentially three overlapping product claim scaffolds:
- Product scaffold A: claim 1 (immediate + release-delaying matrix with defined hydrophilic:insoluble ratio)
- Product scaffold B: claim 29 (same, but the second portion is explicitly “sustained release form”)
- Product scaffold C: claim 43 (same concept with explicit “sustained release formulation” plus co-active language)
A separate method scaffold appears in claim 61:
- Method scaffold: claim 61 ties administration of the claimed product to treating coughing and cough-associated conditions.
What is actually being claimed: drug product “shape” vs “performance”
The polymer ratio and polymer identities are composition anchors. The most design-constraining elements are the PK limitations, especially the “no-drop-below comparator minimum over 12 hours” element and the Cmax equivalence to a specific comparator design. These are not typical for generic design-around strategies because they force a matching serum-time profile under serum analysis.
How broad are the guaifenesin modified-release claims in US 6,955,821?
Broadness is high on polymer identity and some dosage-range knobs, but narrow on functional PK outcomes.
Hydrophilic polymer coverage (claim 2)
Claim 2 provides a long list of acceptable hydrophilic polymers, including:
- natural gums and polysaccharides (e.g., acacia, gum tragacanth, locust bean gum, guar gum, karaya gum, agar, pectin, carrageen, alginate, gelatin, casein, zein, bentonite)
- modified cellulosics (e.g., methylcellulose, hydroxymethylcellulose, hydroxypropyl methylcellulose, hydroxypropyl cellulose, hydroxyethylcellulose, carboxymethylcellulose)
- starch derivatives and related materials (e.g., modified starch derivatives)
This list supports wide formulation flexibility while still keeping claim capture tied to “hydrophilic polymer” as defined by the included set.
Water-insoluble polymer coverage (claim 3)
Claim 3 enumerates:
- polyacrylic acid, acrylic resin, acrylic latex dispersion
- cellulose acetate phthalate and related phthalates and enteric-style polymers (e.g., polyvinyl acetate phthalate, hydroxypropyl methylcellulose phthalate)
This anchors the insoluble/drug-release-delaying matrix behavior.
Key narrowing sub-claim: specific polymer pair
Claim 4 specifically pins:
- hydrophilic polymer = hydroxypropyl methylcellulose (HPMC)
- water-insoluble polymer = an acrylic resin
In enforcement, this provides a narrower “fallback” where both polymers are explicitly defined.
Ratio breadth (independent claims)
Independent claims allow:
- hydrophilic:water-insoluble ratio from about 1:1 to about 9:1
The product claims therefore capture many matrix formulations as long as they remain within that ratio range and meet the PK profile.
Dose and internal proportion ranges (dependent claims)
The excerpted dependent claims set additional boundaries:
- Total guaifenesin dose: 600 mg to 1200 mg (claims 17, 30, 44)
- Guaifenesin (first) to guaifenesin (second) ratios: multiple ranges
- 1:1 to 1:49 (claim 20)
- 2:3 to 1:19 (claim 21; also used later)
- Hydrophilic:insoluble polymer ratio tightening via matrix composition percentages (claim 25)
- Release-delaying matrix includes (by weight):
- 75% to 95% guaifenesin
- 1% to 15% additional drug
- 1% to 10% hydrophilic polymer
- 0.5% to 2.5% water-insoluble polymer
And one additional composition bracket (claim 28) adds a second numeric alternative:
- 80% to 90% guaifenesin
- 3% to 10% additional drug
- 2% to 5% hydrophilic polymer
- 1% to 1.5% water-insoluble polymer
Bilevel tablet vs coating vs capsule
Claims expand product form factor but still within the same functional product concept:
- Bilayer tablet via abutting planar layers (claims 26, 38)
- Coated matrix where sustained/delayed matrix is coated by immediate-release layer (claims 27, 39)
- Capsule-shaped containing immediate + sustained forms (claim 40; also claim 58)
These alternatives broaden manufacturing pathways, so design-around cannot rely solely on changing the unit operation, as long as the two-fraction and PK constraints remain met.
Which pharmacokinetic limitations drive infringement risk?
The PK language is the most litigation-relevant narrowing constraint. In your excerpt, the independent claims use three overlapping PK elements:
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Comparator Cmax equivalence
- “immediate release formulation guaifenesin has a Cmax… equivalent to the Cmax obtained when a dose of a standard immediate release formulation having one third the amount of guaifenesin is dosed”
- This sets a quantitative equivalency requirement tied to a specific comparator structure and dosing factor.
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Tmax and time-to-peak
- “serum concentration… peaks in about an hour”
- This constrains release timing.
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12-hour minimum concentration rule
- “serum concentration… never decreases below the minimum concentration of said standard immediate release formulation over twelve hours”
- This constrains the entire curve shape, not just peak.
The dependent claims add numeric PK thresholds:
- *Cmax ≥ 1900 ng/mL and AUCinf ≥ 7000 hrng/mL** (claims 22, 34, 52)
- *Cmax ≥ 1000 ng/mL and AUCinf ≥ 3500 hrng/mL** (claims 23, 36, 54)
- additional ranges:
- Cmax 1600–2500 ng/mL and AUCinf 5600–8750 hr*ng/mL (claim 33)
- Cmax 800–1250 ng/mL and AUCinf 2800–4375 hr*ng/mL (claim 35; also claim 53)
Enforcement implication: Even if a competitor uses a polymer pair and ratio in range, missing the “equivalence” Cmax and “never below minimum over 12 hours” rule can be argued as noninfringement, depending on claim construction and proof structure.
What polymer ratios and matrix compositions are claimed?
Hydrophilic polymer to water-insoluble polymer ratio
- About 1:1 to about 9:1 in independent product claims.
Matrix percentage composition (release-delaying matrix)
Claim 25 provides a composite matrix weight-percent framework:
- guaifenesin: 75% to 95%
- additional drug: 1% to 15%
- hydrophilic polymer: 1% to 10%
- water-insoluble polymer: 0.5% to 2.5%
Claim 28 provides another bracket:
- guaifenesin: 80% to 90%
- additional drug: 3% to 10%
- hydrophilic polymer: 2% to 5%
- water-insoluble polymer: 1% to 1.5%
Design-around pressure: A generic must show either (a) its delayed/sustained fraction does not fall within the polymer ratio/composition bands, or (b) its PK profile does not satisfy the claim constraints.
What additional drugs are covered alongside guaifenesin?
Independent claims cover “at least one additional drug.” Dependent claims then restrict the additional drug to certain therapeutic classes and enumerate examples.
Class-level co-actives (claim 6)
- antitussive
- decongestant
- antihistamine
- analgesic
- combinations
Specific ingredient coverage (claims 7 and 8)
Claim 7 lists a large set, including:
- antitussive: dextromethorphan hydrobromide
- controlled/opioid antitussive examples: codeine, hydrocodone
- decongestants: phenylephrine hydrochloride, phenylpropanolamine hydrochloride, pseudoephedrine hydrochloride, ephedrine
- antihistamines: multiple (e.g., chlorpheniramine maleate, brompheniramine maleate, doxylamine succinate, diphenhydramine hydrochloride, promethazine, clemastine fumerate, pyrilamine maleate, phenindamine tartrate, brompheniramine)
- analgesic: aspirin, ibuprofen, acetaminophen, naprosin equivalents
Claim 8 narrows further to:
- dextromethorphan hydrobromide, pseudoephedrine hydrochloride, or combination
Practical effect: If a competitor’s product excludes all listed classes, it likely avoids certain dependent claim coverage, but independent claim 1 still allows “at least one additional drug” without naming, unless the patent examiner construction treats the dependent claims as limiting the independent scope or the claim is enforced as a whole. On doctrine-of-claiming, dependent claims add further restrictions; infringement generally requires meeting at least one independent claim plus its additional limitations or meeting a specific dependent combination.
What method-of-use claims are included, and what do they cover?
Claim 61 covers:
- “A method of treating coughing and symptoms or diseases associated with coughing” by administering a therapeutically effective amount of a claimed modified release drug product (claim 1, 43, or 29).
Dependent claims narrow administration:
- oral administration (claim 62)
- additional drug classes and specific enumerations in claims 63–65
- dose and PK-related ranges tied back into the product configuration
Scope consequence
A generic’s manufacturing and sale may be targeted via product claims; method-of-use claims typically matter for post-launch evidence of prescribing and administration, but product formulation is the central issue.
Which claim sub-features create the best litigation fallback positions?
From the claim text provided, key “fallback” anchors include:
- Specific hydrophilic/insoluble polymer pair (HPMC + acrylic resin) (claim 4)
- Specific matrix coated/bilayer/capsule format options (claims 26–28, 38–40, 56–60)
- Specific PK numeric bands
- Cmax/AUCinf threshold pairs (claims 22/23/33/34/35/36, and the duplicates in the 43 scaffolds)
- Additional co-active examples
- especially dextromethorphan + pseudoephedrine (claims 8, 47, 63–65)
These allow enforcement strategies to pick the most provable subset.
What design-around scenarios are likely to fall outside the patent’s claim scope?
Based solely on the excerpted claim language, design-around risk is highest when competitors match all of the following simultaneously: (a) two guaifenesin fractions with stomach bioavailability from an IR portion, (b) delayed/sustained fraction polymer system within the ratio band, (c) defined PK curve constraints including comparator-based equivalence and “no-drop-below minimum over 12 hours,” and (d) optional co-active inclusion within the permitted classes.
Likely outside-scope approaches (in claim-language terms) include:
- Changing hydrophilic:water-insoluble polymer weight ratio outside 1:1 to 9:1
- Using only polymers not enumerated within claim 2 and/or not matching claim 3’s insoluble list (depending on whether claim interpretation treats the lists as exhaustive)
- Failing the comparator Cmax equivalence and/or the “never below minimum concentration over 12 hours” constraint
- Changing unit form to avoid bilayer/coat/capsule structures is less likely to avoid capture because independent claims allow flexible product shapes via dependent alternatives; the critical issue remains the two-fraction structure and PK.
How does 6,955,821 compare across the claim scaffolds (1 vs 29 vs 43)?
Claim 1 vs 29 vs 43: all share the same two-fraction concept and polymer ratio band. Differences in your excerpt are primarily wording and placement:
- claim 1 uses “release-delaying matrix”
- claim 29 uses “sustained release form”
- claim 43 uses “sustained release formulation”
- dependent add-ons differ slightly in wording but map to the same PK and composition architecture
Litigation impact: A competitor cannot evade infringement by exploiting wording differences between “matrix” and “sustained release form” if its accused product performs equivalently and meets the other elements.
Key Takeaways
- US 6,955,821 is built around a two-fraction guaifenesin modified-release oral product: an IR stomach-bioavailable fraction plus a hydrophilic + water-insoluble polymer delayed/sustained fraction.
- The hydrophilic:water-insoluble polymer weight ratio is about 1:1 to about 9:1, with extensive enumerated polymer examples.
- The strongest claim narrowing comes from PK limitations: Cmax equivalence to a standard IR comparator at one-third dose, Tmax about 1 hour, and a 12-hour rule that serum concentration never decreases below the comparator minimum.
- Co-formulation scope is broad in functional terms (“at least one additional drug”) but dependent claims target common cold/cough actives, including dextromethorphan and pseudoephedrine.
- Form factor alternatives (bilayer tablet, coated matrix, capsule) appear in dependent claims, so product shape changes are less likely to defeat scope than changing polymer system or PK performance.
FAQs
1) What does “Cmax equivalent to a standard immediate release formulation having one third the amount” mean for infringement analysis?
It is a PK equivalency requirement tying the accused product’s IR fraction exposure to a comparator design using a one-third dose standard; infringement depends on meeting the claim’s defined equivalence standard.
2) Does the patent cover guaifenesin combination products with dextromethorphan and pseudoephedrine?
Dependent claims expressly cover combinations including dextromethorphan hydrobromide and pseudoephedrine hydrochloride (or combinations), and independent claims allow “at least one additional drug.”
3) Can a generic avoid infringement by using different tablet shapes like a monolithic matrix instead of bilayer?
The independent claims still require the two-fraction structure and the polymer system plus PK constraints, so changing from bilayer/coated structures to a different format is not sufficient if the functional elements remain.
4) What polymer ratio range is claimed for the release-delaying or sustained-release fraction?
The hydrophilic polymer to water-insoluble polymer weight ratio is about 1:1 to about 9:1.
5) Which numeric PK thresholds are explicitly called out in dependent claims?
Examples include Cmax ≥ 1900 ng/mL and AUCinf ≥ 7000 hrng/mL and Cmax ≥ 1000 ng/mL and AUCinf ≥ 3500 hrng/mL, plus intermediate bands such as Cmax 800–1250 ng/mL and *AUCinf 2800–4375 hrng/mL**.
References
No external sources were provided in the prompt; only the claim text of US 6,955,821 was used.
