Details for Patent: 6,399,079

Summary for Patent: 6,399,079

Title:	Spill resistant pharmaceutical compositions in semi-solid form
Abstract:	A spill-resistant pharmaceutical formulation for oral administration from a squeezable container comprises a pharmaceutical agent in a suitable vehicle comprising a liquid base and a thickening agent, the formulation consisting of mutually compatible components and having the following properties: a viscosity within the range of about 7500 to about 12,500 cps using a Brookfield Viscometer with a ‘C’ spindle with Helipath movement at a spindle speed of 10 rpm and 20-25° C., a viscometric yield value of a semi-solid, a spill-resistant consistency permitting the composition to be squeezed by light manual pressure through a channel, to spread in a spoon bowl sufficiently quickly for accurate measurement, and to remain in the spoon bowl without spilling on spoon inversion, tilting at 90 degrees, and vibration, homogeneity such that the components do not separate under conditions of use, and a storage stability such that the foregoing properties are retained for at least two years shelf life. A method for producing a formulation for a spill-resistant pharmaceutical composition comprises combining a per-unit dose effective amount of a pharmaceutical agent with suitable vehicle components comprising a liquid base and a thickening agent, and testing the formulation for acceptance criteria.
Inventor(s):	Rakesh Mehta, Dan Moros
Assignee:	Taro Pharmaceutical Industries Ltd
Application Number:	US09/549,148
Patent Claim Types: see list of patent claims	Composition; Formulation; Compound; Dosage form;

United States Patent 6,399,079: Scope, Claim Structure, and US Landscape

What does US 6,399,079 claim protection cover?

US 6,399,079 is directed to pharmaceutical formulations that are:

• Dispensed from a squeezable container (oral administration),
• Homogeneous semi-solids that spread quickly in a spoon while retaining spill resistance under defined spoon-motion tests,
• Built from a liquid base and a thickening system that is narrowly defined by component classes and quantitative limits,
• Defined by rheology and storage stability (viscosity ranges, yield behavior, and stability after elevated temperature storage).

The core protective concept is a specific rheological “behavior set” (viscosity + yield + spill resistance + spreading time + stability) achieved using a particular thickening system:

• Cellulose derivatives at less than about 2 wt% by volume, and
• Water-soluble carboxyvinyl polymer (CVP) at less than 1 wt% by volume (with narrower dependent limits).

Claims also cover specific liquid base compositions (notably glycerin and optionally propylene glycol) and pharmaceutical agent lists that are broad across therapeutic categories and then narrowed to named actives.

What are the independent claim pillars?

Two independent-style claims appear in the provided text: claim 1 and claim 26. Both share the same technical spine; claim 26 is effectively a more constrained restatement emphasizing glycerin-based base and viscosity/stability after storage.

Independent Claim 1 (technical spine)

Claim 1 requires all of the following elements:

A. Dosage form / container

• “Pharmaceutical formulation for oral administration from a squeezable container.”

B. Composition architecture

• “Pharmaceutical agent in a vehicle comprising a liquid base and a thickening agent”
• “formulation consisting of mutually compatible components”

C. Thickening agent component classes and quantitative ceilings

• Thickening agent comprises:
  • cellulose derivatives: < about 2 wt% by volume
  • water-soluble carboxyvinyl polymer: < 1 wt% by volume

D. Rheology and semi-solid behavior

• “initial viscosity” ~5,000 to ~12,500 cps
• “viscometric yield value of a semi-solid”

E. Spill resistance and spoon handling performance (multi-part test envelope)

• Dispensing through a 1–5 mm channel by light manual pressure
• Spreads in a spoon bowl “sufficiently quickly for accurate measurement”
• Remains in spoon bowl without spilling for:
  • at least ~1 second and less than ~20 seconds on spoon tilting
  • at least ~30 seconds upon spoon vibration

F. Homogeneity

• “components do not separate under conditions of use”

G. Storage stability

• “storage stability” is a required functional attribute, reinforced by downstream dependent claims that set explicit viscosity behavior after storage.

Independent Claim 26 (glycerin-centric, stability-quantified restatement)

Claim 26 requires:

• liquid base is 30% to 50% glycerin
• same viscosity/yield and spoon behavior envelope
• same homogeneity requirement
• storage stability for at least 3 months at elevated temperature with viscosity change constrained to 50% less to 100% more than initial viscosity.

How do the dependent claims narrow the numeric space?

The dependent claims set multiple “gateposts” that define likely infringement and likely design-around levers.

Rheology constraints after stress (storage)

• Claim 2: viscosity 7,500 to 25,000 cps after 3 months at 40°C and 75% RH
• Claim 3: viscosity 7,500 to 12,500 cps after storage
• Claim 25: after 3 months elevated temperature, viscosity remains within 50% less to 100% more of initial

The combination of initial viscosity window and post-storage viscosity window is a key narrowing mechanism. Even if a formulation meets spoon behavior, it must survive defined thermal stress without viscosity drifting outside the allowed band.

Thickener concentration windows

• Claim 4: CVP 0.25 to <1 wt% (note: phrased “weight % by volume” in the text)
• Claim 8: CVP 0.25 to 0.5 wt% by volume
• Claim 6: explicit thickener example: sodium carboxymethylcellulose ~0.9% + microcrystalline cellulose ~0.9%
• Claim 7: cellulose derivatives <2 wt% by volume, plus glycerin/sorbitol solution at ~70% in water, combined glycerin+sorbitol solution at ~40%
• Claim 10: liquid base includes propylene glycol 10–85 wt% by volume with cellulose derivatives <2 wt% by volume
• Claim 27: cellulose derivatives 0.9 to 2.5 wt% (note this partially conflicts directionally with claim 1’s “< about 2 wt%”; it likely reflects dependent variant boundaries within the claim set as written)

Spill resistance and time targets

• Claim 9: remain without spilling 1–4 seconds on spoon tilting (subset of claim 1’s 1–20 seconds)
• Claim 19: remain without spilling 20–30 seconds on spoon inversion (note it overlaps but is distinct from tilting language)
• Claim 21: remain without spilling 1–4 seconds on spoon inversion (again, specific subset)

Spreading/dispensing articulation

• Claim 17: spreads “as quickly as honey” and spill resistance greater than honey (functional/relative)
• Claim 18: spread to edge of spoon within ~5 seconds
• Claim 20: readily consumed from spoon bowl
• Claim 26 and claim 1 both require dispensing from squeeze container through a 1–5 mm channel under light manual pressure.

Liquid base compositions

• Claim 5: liquid base comprises glycerin and sorbitol
• Claim 13: glycerin 30% to 50%
• Claim 14: glycerin plus propylene glycol up to ~25 wt%
• Claim 15: liquid base comprises propylene glycol
• Claim 16: liquid base comprises glycerin
• Claim 17/18/21 add honey-like spreading and timing
• Claim 28: liquid base about 50% glycerin, thickener CVP 0.25 to 1 wt%
• Claim 29: liquid base further comprises propylene glycol

Viscosity size gates

• Claims 23–24: viscosity at least 7,000 cps and at least 7,500 cps
• Claim 33–34: (claim 26 variants) viscosity at least 7,000 cps and at least 7,500 cps
• Claim 35: viscosity 7,000 to 12,500 cps
• Claim 36: viscosity at least 7,500 cps
• Claim 37–39: claim 32 variants (viscosity thresholds at least 5,000/7,000/7,500 cps)

How broad is the pharmaceutical agent coverage?

The patent provides both: 1) Therapeutic class coverage (claim 11), and
2) Named active ingredient coverage (claim 12).

Therapeutic categories (Claim 11)

Analgesics, NSAIDs, antihistamines, cough suppressants, expectorants, bronchodilators, anti-infectives, CNS actives, cardiovascular drugs, antineoplastics, cholesterol-lowering drugs, anti-emetics, vitamin/mineral supplements, and fecal softeners.

Named active ingredients (Claim 12)

A list including: acetaminophen, aspirin, ibuprofen, diphenhydramine, dextromethorphan, guaifenesin, pseudoephedrine, carbidopa, levodopa, terfenadine, ranitidine, ciprofloxacin, triazolam, fluconazole, propranolol, acyclovir, fluoxetine, enalapril, diltiazem, lovastatin and pharmaceutically acceptable salts/esters.

Practical implication: the patent’s formulation system is the protected invention; the actives are used as interchangeable payloads within the structural/rheological requirements.

What about claims 30–32: different formulation definition style?

Claims 30–32 are more composition-statements and dispensing behavior statements, with different quantitative framing.

Claim 30

A pharmaceutical composition comprising:

• CVP 0.25% to 0.5% by weight
• liquid base comprising glycerin and/or propylene glycol
• pharmaceutical agent
• “homogeneous semi-solid” and dispensable from squeezable container into a spoon
• “spilling from the spoon within 20 seconds after tilting the spoon”

This is a noticeable behavioral formulation: it converts “spill resistant consistency permitting remain without spilling” (claim 1 language) into “spilling within 20 seconds” (claim 30). The claim set therefore covers both “spills after a defined window” and “does not spill for a defined window,” depending on the dependent wording.

Claim 31

Actives limited to guaifenesin, dextromethorphan, pseudoephedrine, acetaminophen, and combinations.

Claim 32

A pharmaceutical composition comprising:

• CVP ≤ 1.0% by weight
• liquid base: glycerin > 15% plus propylene glycol
• pharmaceutical agent
• homogeneous semi-solid dispensable from squeezable container
• viscosity < 12,000 cps

This creates an additional design space: relatively higher glycerin fraction with propylene glycol and a lower viscosity ceiling.

Where is the overlap and where are the internal tensions?

Several dependent claims sit close to each other but can pull in different quantitative directions:

• Cellulose derivative cap: claim 1 says “< about 2 wt% by volume,” while claim 27 allows 0.9 to 2.5 wt%. This can matter in claim construction, since both could be read as alternative dependent embodiments.
• CVP units: some claims describe “weight % by volume,” others say “by weight,” which can change literal scope depending on how the specification reconciles units.
• Spilling language: claim 1 emphasizes “remain… without spilling for at least 1 second but less than 20 seconds,” while claim 30 includes “spilling… within 20 seconds.” That can be read as complementary (spill after window) or as distinct performance definitions.

From an infringement and freedom-to-operate perspective, literal coverage is most sensitive to:

• CVP and cellulose derivative concentration limits,
• initial and post-storage viscosity windows,
• spoon tilting/inversion/vibration time windows,
• the requirement of dispensing through a 1–5 mm channel under light manual pressure from a squeezable container.

Patent landscape: what neighboring US IP is likely to exist?

This is a formulation-and-device interface story: “squeezable container” plus “spoon handling rheology” is a niche but not unique concept across pediatric and geriatric oral dosage forms. A typical US landscape for this space clusters around:

• viscosifying systems (cellulose derivatives, CVP, carbomers, PVP-related systems),
• semi-solid spoonable vehicles (glycerin/propylene glycol/sorbitol),
• container formats for dose-delivery (squeeze tubes, capillary tips, channel dispensing),
• stability and viscosity drift under thermal stress.

Likely competitive claim approaches around this patent

Because claim 1 locks on to:

• thickener class (cellulose derivatives + CVP),
• concentration ceilings,
• viscosity and yield behavior,
• spoon tests for spill resistance and spread time,

competitors usually distinguish via at least one axis: 1) Change the thickener chemistry away from CVP or cellulose derivatives (replace with non-cellulose/non-carboxyvinyl polymers). 2) Reformat rheology behavior so viscosity/yield or spoon times fall outside defined windows. 3) Change liquid base ratios or eliminate required base constituents (e.g., no glycerin at required fraction). 4) Change container dispense pathway so the formulation is not dispensed through the specified 1–5 mm channel under “light manual pressure,” or does not meet the specified semi-solid yield behavior used to generate the spoon behavior envelope. 5) Alter stability behavior so viscosity shift after defined elevated storage falls outside the claimed band.

What is the strongest business reading of US 6,399,079 claim scope?

US 6,399,079 is likely strongest against products that are essentially:

• spoon-dosing semi-solids in a squeeze package,
• using a glycerin-based vehicle and a cellulosic/CVP thickener blend,
• tuned to specific viscosity and yield behavior,
• engineered so caregivers can dispense and measure accurately with the defined spill resistance and spread timing tests,
• and with stability claims tied to viscosity retention after defined elevated conditions.

Conversely, the patent is weaker as a blanket cover if a competitor:

• uses a different polymer thickener system,
• accepts different spoon pour and spill characteristics,
• uses non-glycerin or substantially different liquid base fractions,
• or fails the viscosity/yield and post-storage bands.

Key claim-to-parameter mapping (for infringement triage)

Parameter	Where it appears	Numeric gate (as written in claims)
CVP presence	Claim 1, 4, 8, 27, 28, 30, 32	“<1 wt% by volume” (C1); 0.25–<1 (C4); 0.25–0.5 (C8); 0.25–1 (C28); 0.25–0.5 wt% (C30); ≤1.0 wt% (C32)
Cellulose derivative presence	Claim 1, 6, 7, 10, 27	“< about 2 wt% by volume” (C1); example 0.9%+0.9% (C6); “< about 2” plus other base (C7); “< about 2” plus PG window (C10); “0.9–2.5” (C27)
Initial viscosity	Claim 1, 26	~5,000 to ~12,500 cps
Yield value	Claim 1, 26	“viscometric yield value of a semi-solid”
Spoon tilting spill resistance	Claim 1, 9, 21	“at least 1 second but <20 seconds” (C1); 1–4 seconds (C9); 1–4 seconds on inversion (C21)
Spoon vibration spill resistance	Claim 1	at least 30 seconds
Dispense channel geometry	Claim 1, 26	1 to 5 mm channel
Storage stability (3 months)	Claim 2, 3, 25, 26	40°C/75%RH viscosity ranges (C2, C3); or 50% less to 100% more (C25, C26)
Liquid base glycerin fraction	Claim 13, 26, 28	30–50% (C13, C26); about 50% (C28)
Propylene glycol involvement	Claim 10, 14, 15, 29, 32	up to 25 (C14); 10–85 (C10); glycerin + PG (C32)
Overall agent universe	Claim 11, 12	broad categories + named actives

What does this mean for R&D and investment decisions?

1) The protected invention is formulation behavior, not just ingredient presence. Any FTO analysis must test viscosity, yield, spoon-timing behavior, and post-storage viscosity drift against the parameter gates. 2) Polymer system is the most direct lever. The thickener system is restricted to cellulose derivatives and water-soluble carboxyvinyl polymer (and CVP concentration windows). Swapping the thickener chemistry is the fastest way to reduce literal infringement risk. 3) Device pathway matters. The claim ties dispensing to a squeezable container with a specified channel (1–5 mm). If commercial dispensing mechanics differ meaningfully, literal alignment weakens. 4) Stability is part of the bargain. Even if spoon performance is met at release, viscosity drift after elevated storage creates a separate infringement gate.

Key Takeaways

• US 6,399,079 protects squeezable-container, spoon-dosed semi-solid pharmaceuticals with a defined rheology and spoon-spill performance envelope.
• The formulation must use a thickener system of cellulose derivatives (<~2 wt% by volume) and water-soluble carboxyvinyl polymer (<1 wt% by volume), with dependent claims tightening CVP and specifying examples (e.g., sodium carboxymethylcellulose and microcrystalline cellulose).
• The formulation must have initial viscosity ~5,000–12,500 cps and a semi-solid yield value, and must pass spoon tilting/vibration spill resistance and spreading within ~5 seconds type behavior requirements.
• Glycerin-centric vehicles (e.g., 30–50% glycerin) are prominent in the independent restatement, with optional propylene glycol and sorbitol variants.
• Post-storage viscosity behavior after 3 months at elevated conditions is a central limiter (including defined ranges under 40°C and 75% RH).
• Competitive designs are most likely to avoid infringement by changing thickener chemistry, rheology windows, spoon behavior timing, or storage-viscosity retention.

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FAQs

1) What is the single most important technical limitation in US 6,399,079?
The formulation’s rheological and spoon handling profile: initial viscosity (~5,000–12,500 cps) plus “semi-solid” yield behavior and quantified spill resistance on spoon tilting/inversion and on spoon vibration, alongside homogeneity and storage stability.

2) Does the patent protect a specific drug?
No. It protects a formulation platform for oral administration; it lists broad therapeutic classes and then enumerates named actives (e.g., acetaminophen, ibuprofen, dextromethorphan, guaifenesin, pseudoephedrine, etc.).

3) How do CVP and cellulose derivatives drive scope?
Claims require water-soluble carboxyvinyl polymer and cellulose derivatives within specific concentration ceilings/windows, which act as direct literal infringement thresholds.

4) What dosing mechanics are tied to the claims?
Dispensing from a squeezable container through a 1 to 5 mm channel by light manual pressure is explicitly recited and is part of the protected behavior.

5) Can competitors design around by altering viscosity only?
Likely. The claims include tight ranges for initial viscosity and additional constraints after 3 months elevated storage. If a formulation misses either the initial rheology window or the post-storage viscosity retention band, it can fall outside literal scope even if spoon behavior is similar.

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References

1. United States Patent 6,399,079, claims 1-39 (as provided in the prompt).

Drugs Protected by US Patent 6,399,079

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate

International Family Members for US Patent 6,399,079

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	312598
Austria	411796
Australia	2003271358