United States Patent 9,572,819: Scope, Claim Architecture, and US Landscape for Celecoxib Stable Oral Liquid
What does US 9,572,819 claim cover at the formulation level?
US Patent 9,572,819 is directed to a stable oral liquid pharmaceutical composition containing celecoxib and a tightly constrained combination of excipients that together govern (i) solubilization capacity, (ii) avoidance of precipitation under fasted gastric conditions, and (iii) physical properties tied to liquid dosage performance.
Core claim anchor (Claim 1)
Claim 1 defines the invention by simultaneously requiring:
- Active: therapeutically effective amount of celecoxib
- Solubilizer: at least one solubilizer present at 35% w/w to 45% w/w
- Medium chain glyceride: at least one medium chain glyceride (structurally specified in dependent claims)
- Polar solvent: at least one polar solvent (structurally specified in dependent claims)
- Other excipients: at least one pharmaceutically acceptable excipient
- Stability/precipitation criterion: no precipitation in Fasted-State Simulated Gastric Fluid (FaSSGF) at:
- pH 2.0
- 37°C ± 0.5°C
- 50 rpm stirring
- measured at 60 minutes
This claim is written as a closed functional gate (no precipitation under defined stress conditions) plus quantitative excipient bands (solubilizer at 35-45% w/w).
Structured dependent layering (Claims 2-23)
Claims 2 through 23 progressively lock down composition, excipient selection, physicochemical parameters, and performance readouts.
(A) “Essentially free” carve-out (Claim 2)
Claim 2 narrows Claim 1 by requiring the composition be essentially free of precipitation inhibitors from a named group, including:
- Polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer
- Polyoxyethylene-polyoxypropylene block copolymers
- Pluronics
- Polyvinylpyrrolidone
- Cellulosic polymers, including hydroxypropyl cellulose and hydroxypropyl methylcellulose
This matters for infringement because many celecoxib oral liquid approaches lean on polymeric precipitation inhibitors to stabilize supersaturation. The patent’s coverage explicitly excludes that strategy.
(B) Specific solubilizer identity (Claim 3)
Claim 3 limits the solubilizer to:
- Polyethoxylated castor oil
- Lauryl macrogolglyceride
- or combinations
(C) Specific medium chain glyceride identity (Claim 4)
Claim 4 limits the medium chain glyceride to:
- Glyceryl tricaprylate/tricaprate
- Glyceryl monocaprylate
- or combinations
(D) Specific polar solvent universe (Claim 5)
Claim 5 limits polar solvents to mixtures selected from:
- Propylene glycol
- PEG 400 to PEG 1000
- Glycerin
- C2 to C8 mono- and poly-alcohols
- C7 to C18 linear or branched alcohols
- Water
- mixtures thereof
(E) Celecoxib amount band (Claim 6)
Claim 6: celecoxib is 1% to 80% w/w.
(F) Ratio windows that control formulation space (Claims 7, 9, 23)
- Claim 7: solubilizer:celecoxib = 4.0:1.0 to 20:1.0
- Claim 9: solubilizer:polar solvent = 0.60:1.00 to 1.8:1.00
These ratios reduce design-around by making it harder to keep the solubilizer in band while changing solvent fraction.
(G) Medium chain glyceride amount (Claim 10)
Claim 10: glyceride present at 5% to 75% w/w.
(H) Droplet size criterion (Claim 11)
Claim 11 adds:
- mean oil droplet size ≤ 500 nm
tested in 250 mL FaSSGF under:
- pH 2.0
- 37°C ± 0.5°C
- 50 rpm
This indicates the formulation functions as a dispersion/emulsion-like system where droplet size helps prevent precipitation or phase separation.
(I) Liquid physical properties (Claims 12-15)
Claim 12: viscosity 20 cps to 1000 cps
Claim 13: density 0.8 g/cm³ to 2 g/cm³
Claim 14: transmittance ≥ 40%
Claim 15: pH 3 to 7
Together they target a liquid that is physically stable and presentable (clarity/transmittance) while remaining orally acceptable.
(J) “Dose reduction” assertions tied to capsule comparisons (Claims 16-21)
Claims 16-21 set celecoxib amounts as at least 40% to 70% less than “conventional celecoxib in 400 mg oral capsules,” with example dose points:
- Claim 17: 240 mg (~40% less)
- Claim 19: 180 mg (~55% less)
- Claim 21: 120 mg (~70% less)
This is a performance-anchored claim angle. While it is still a formulation claim, it can affect literal scope if an accused product’s celecoxib dose is outside these bands.
(K) Fasted pharmacokinetic windows (Claim 22)
Claim 22 expands scope from formulation to pharmacokinetic outcomes under fasting oral administration:
- AUC(0-15 min): 10 to 80 ng·h/mL
- AUC(0-30 min): 80 to 400 ng·h/mL
- AUC(0-1 hr): 400 to 1500 ng·h/mL
- AUC(0-2 hr): 1000 to 4000 ng·h/mL
- AUC(0-t) ≥ 2000 ng·h/mL
- AUC(0-∞) ≥ 2000 ng·h/mL
- Tlag ≤ 8 minutes
This creates a harder-to-design-around infringement posture for products that achieve different exposure profiles.
What alternative formulation claim variants exist?
US 9,572,819 includes additional composition claims that specify release and compositional structure beyond Claim 1.
Release-performance claim (Claim 24)
Claim 24: 100 mg to 250 mg celecoxib with the same solubilizer band (35-45% w/w) and medium chain glyceride plus polar solvent. It requires one of two release outcomes in:
- 900 mL 0.01N HCl + 0.5% sodium lauryl sulfate
- USP Type 2 apparatus with sinkers
- 50 rpm, 37°C
- either:
- ≥70% release at 10 minutes, or
- ≥80% release at 15 minutes
This claim ties scope to dissolution/release kinetics under surfactant gastric-like conditions.
Polar-solvent phase diagram constraint (Claim 28)
Claim 28 defines a stable composition where polar solvent is:
- ethanol and glycerin mixture
and the composition must fall within the shaded region of a phase diagram (Fig. 1) with boundary-defined ratios given via six base-composition points (a-f), expressed as:
- base composition : ethanol : glycerin
- a) 0.200 : 0.024 : 0.712
- b) 0.200 : 0.376 : 0.360
- c) 0.200 : 0.400 : 0.336
- d) 0.536 : 0.400 : 0.000
- e) 0.900 : 0.036 : 0.00
- f) 0.900 : 0.00 : 0.036
This claim is a geographic restriction in formulation space, not just range bands, which can reduce workability for design-arounds that otherwise satisfy excipient percentages.
What method-of-use claims are included?
The patent includes treatment method claims that stay linked to the formulation.
Treatment claims (Claims 25-27)
- Claim 25: administering the stable oral liquid with the Claim 1-type formulation; formulation is essentially free of precipitation inhibitors.
- Claim 26: pain associated with migraine.
- Claim 27: method where celecoxib amount is sufficient to render subject pain-free within 2 hours.
These claims do not add new formulation features, but can constrain infringement at the indication and endpoint level if clinical labeling or trials match the migraine/pain-free timing.
How is claim scope likely to be interpreted in practice?
The claim set uses a layered strategy: (i) excipient identity and quantitative bands, (ii) stability stress tests (FaSSGF, 60 min, pH 2, 37°C, 50 rpm), and (iii) physical performance surrogates (droplet size, viscosity, density, transmittance), then (iv) bio-performance (PK windows and Tlag) and (v) specific release outcomes.
“Hard gates” vs “soft gates”
| Layer |
Examples in claims |
Practical effect |
| Hard gates (literal tests) |
No precipitation in FaSSGF at pH 2.0 for 60 min (Claim 1); droplet size ≤ 500 nm (Claim 11); release % thresholds in USP apparatus (Claim 24) |
Strong infringement leverage where testing can reproduce claimed conditions |
| Quantitative bands |
Solubilizer 35-45% (Claim 1); solubilizer:celecoxib ratios (Claim 7); solubilizer:polar solvent (Claim 9); medium chain glyceride 5-75% (Claim 10) |
Tight formulation boundaries; design-arounds must move multiple variables simultaneously |
| Identity limits |
Solubilizers limited (Claim 3), glycerides limited (Claim 4), solvents limited (Claim 5) |
Narrow material substitution options |
| Performance windows |
AUC and Tlag (Claim 22); pain free within 2 hours (Claim 27) |
Infringement can depend on clinical data or bioassay outcomes |
What design-arounds are foreclosed by the claim language?
Based on the explicit limitations, the patent blocks several straightforward substitution routes.
1) Precipitation inhibitor polymer route is expressly excluded via Claim 2’s “essentially free” language covering polymers such as PVP and HPMC/HPCH and Pluronics.
2) Solubilizer concentration is constrained to 35-45% w/w, not just “high” solubilization. Even if other features are met, moving outside this band weakens Claim 1 literal coverage.
3) Key excipient identity limits what can replace solubilizer and medium chain glyceride. Substituting a different surfactant or a different glyceride class risks falling outside Claims 3 and 4.
4) Oil droplet size is constrained to ≤500 nm in FaSSGF, tying stability to microstructure.
5) Phase diagram restriction in Claim 28 can constrain ethanol/glycerin formulations even if they are within general percentage bands.
Where the claim set is likely strongest vs weakest
Strongest infringement positions
- Competitors launching an oral liquid celecoxib with:
- solubilizer at 35-45% w/w
- using polyethoxylated castor oil and/or lauryl macrogolglyceride
- medium chain glycerides such as glyceryl tricaprylate/tricaprate or glyceryl monocaprylate
- and demonstrating no precipitation in FaSSGF at the specified conditions
- Products that also meet:
- droplet size ≤ 500 nm (Claim 11)
- viscosity 20-1000 cps, density 0.8-2, transmittance ≥40%, pH 3-7 (Claims 12-15)
Weakest infringement positions
- Products that:
- rely on the named precipitation inhibitors (Claim 2) to stabilize supersaturation
- use solubilizers not in Claim 3 (even if solubilizing capacity is similar)
- or use medium chain glycerides not in Claim 4
- Products that satisfy stability under other in vitro conditions but fail the specific FaSSGF time/temperature/stirring/pH test conditions.
Patent landscape signals for US 9,572,819 (what matters for freedom-to-operate)
A robust landscape analysis requires bibliographic data (application family, assignee, priority dates, expiration, prosecution history, and cited references) and US publication/continuation mapping. The prompt provides only the claim text; no bibliographic record is included.
Given the constraints, the only defensible “landscape” observations are structural: US 9,572,819 is an excipient-and-stability-driven oral liquid patent that will typically sit among a cluster of celecoxib formulation patents covering:
- solid dosage reformulations vs oral liquids
- solubilizer systems (surfactant/castor derivatives and macroglycerides)
- supersaturation control and precipitation inhibition
- emulsion droplet size and gastric stability
- pharmacokinetic outcomes in fasting conditions
Key Takeaways
- US 9,572,819 is tightly focused on a celecoxib stable oral liquid defined by solubilizer concentration (35-45% w/w), specific solubilizer and glyceride identities, and a no-precipitation FaSSGF stability gate at pH 2.0, 37°C, 50 rpm, 60 min (Claim 1).
- The patent blocks common formulation workarounds by requiring the composition be essentially free of specific precipitation inhibitor polymers (Claim 2).
- Scope is further constrained by microstructure (oil droplet size ≤ 500 nm), physical properties (viscosity/density/transmittance/pH), and performance claims tied to release kinetics (Claim 24) and fasted PK windows/Tlag (Claim 22).
- Design-arounds that change only one variable (for example swapping solvents while keeping solubilizer in band) may still fall outside the claim due to the multi-parameter coupling across identity, ratio, stability, droplet size, and performance.
FAQs
1) Is US 9,572,819 mainly a formulation patent or a method patent?
It is primarily a formulation patent (Claims 1-24, 28), with method-of-treatment claims tied to administering that formulation for pain/migraine (Claims 25-27).
2) What single test most directly defines literal coverage in the broadest claim?
Claim 1 requires no precipitation in FaSSGF pH 2.0 at 37°C ± 0.5°C under 50 rpm stirring at 60 minutes.
3) Can a competitor avoid infringement by using different precipitation inhibitors?
Claim 2 requires the composition be essentially free of a defined list of precipitation inhibitor polymers and Pluronics, so using those materials can conflict with literal scope.
4) Does the patent require an emulsion-like system?
Claim 11 requires mean oil droplet size ≤ 500 nm in FaSSGF, which aligns with an emulsion/dispersion system where droplet size is controlled.
5) Do the claims require clinical PK data for infringement?
Some dependent claims (like Claim 22) explicitly require PK parameter windows, but independent coverage still exists through the formulation and stability limitations in Claim 1.
References
[1] United States Patent No. 9,572,819. (Claims as provided in prompt text).
