United States Patent 8,927,606 Scope and Claims for Tyloxapol-Stabilized Ophthalmic 2-Amino-3-(4-bromobenzoyl)phenylacetic Acid (Bromophenylacetic Acid) Sodium Salt
United States Patent 8,927,606 claims a specific ophthalmic formulation-and-use package: a stable aqueous liquid ophthalmic preparation where the sole active ingredient is 2-amino-3-(4-bromobenzoyl)phenylacetic acid (or pharmacologically acceptable salt or specified hydrates) in defined concentration ranges, stabilized by tyloxapol at defined w/v % levels, with additional constraints around excipients, stability after heat storage, preservative efficacy, and optional excipient exclusions (e.g., no mannitol). The independent claim set is method-of-treatment, but the method is structurally constrained by the composition and quality/stability parameters of the administered liquid.
What does US Patent 8,927,606 claim: method-of-treating ophthalmic inflammation with tyloxapol-stabilized bromophenylacetic acid?
Short answer: The patent claims administering to an eye a stable aqueous ophthalmic liquid containing:
- Sole active ingredient: 2-amino-3-(4-bromobenzoyl)phenylacetic acid (or salt/hydrate)
- Stabilizer: tyloxapol at 0.01–0.05 w/v %
- Formulation purpose: ophthalmic administration
- Dosing: dose and frequency effective to treat inflammatory disease
- Disease scope: anterior and/or posterior segment; includes postoperative inflammation
Independent claim scope (high-level boundaries)
Claim 1 (core):
- Method for treating an inflammatory disease of an eye via administering a stable aqueous liquid comprising:
- First component: 2-amino-3-(4-bromobenzoyl)phenylacetic acid or a pharmacologically acceptable salt/hydrate, including at least one of 1/2 hydrate, 1 hydrate, 3/2 hydrate
- First component is the sole pharmaceutical active ingredient
- Second component: tyloxapol, present in an amount sufficient to stabilize the first component
- Preparation is formulated for ophthalmic administration
- Administration at effective dose and frequency
Claims 11 and 19 (additional independent claim scaffolds):
- Claim 11 adds a quantified stability criterion: >90% of the original first component remains after 60°C for 4 weeks.
- Claim 19 adds an exclusion: the liquid preparation does not include mannitol.
Across all independent claim variants, the patent’s practical claim boundary is the combination of:
- identity of the active (with hydrate/salt restrictions),
- sole-active requirement,
- tyloxapol stabilization, and
- formulation parameters that make the liquid “stable” and fit ophthalmic use, including optional excipient systems and testable stability/performance metrics.
Method-of-treatment claims: what is actually “the claimed invention”?
Even though the claims are written as methods, infringement turns on the administered product’s composition and quality characteristics:
- If a competitor delivers a different active, the “sole pharmaceutical active ingredient” requirement breaks the claim.
- If tyloxapol is absent or not present at stabilizing-effective levels, the claim fails.
- If the administered product omits required quality attributes (for claims that require stability >90% after heat, or preservative efficacy criteria, or no mannitol), the claim fails.
What inflammatory eye diseases are covered: anterior vs posterior segment and postoperative inflammation?
Short answer: The patent covers inflammatory disease affecting anterior and/or posterior segments, and explicitly includes postoperative inflammation.
Claim mapping to disease types
- Claim 2: inflammatory disease of anterior or posterior segment
- Claim 3: disease is postoperative inflammation
- Claim 13 / 14: repeats anterior/posterior and postoperative inflammation for the claim 11 scaffold
- Claim 20 / 21: repeats anterior/posterior and postoperative inflammation for the claim 19 scaffold
Practical implication: The patent is not confined to a single ophthalmic indication (e.g., only uveitis or only post-cataract). It is broad at the disease level but tied to the same formulation and stability package.
How does US 8,927,606 define the active ingredient: 2-amino-3-(4-bromobenzoyl)phenylacetic acid salts and specified hydrates?
Short answer: The first component must be 2-amino-3-(4-bromobenzoyl)phenylacetic acid or a pharmacologically acceptable salt or a hydrate that includes 1/2 hydrate, 1 hydrate, and/or 3/2 hydrate.
Claim 1 active-ingredient constraints
- The active can be:
- free acid, or
- pharmacologically acceptable salt, or
- specified hydrates:
- 1/2 hydrate
- 1 hydrate
- 3/2 hydrate
- Claim 4: narrows to sodium salt.
Sodium salt embodiments with tighter ranges
- Claim 5: first component is sodium salt; tyloxapol 0.01–0.05 w/v %; sodium salt 0.01–0.2 w/v %
- Claim 6: sodium salt 0.02–0.1 w/v %
- Claim 8: sodium salt about 0.1 w/v %
- Claim 23: ties sodium salt range 0.05–0.2 w/v %, while tyloxapol and other parameters are fixed
- Claim 24: sodium salt 0.02–0.1 w/v %
- Claim 27: again ties sodium salt 0.02–0.1 w/v % in the claim 19 dependent cluster
Practical implication: A generic “same drug, different salt form” strategy is likely blocked where the claim requires a specified hydrate or specifically the sodium salt. Salt/hydrate engineering can matter for design-around depending on which dependent claims are asserted.
What is tyloxapol’s role: stabilization amount and concentration windows?
Short answer: Tyloxapol is required as the stabilizing second component, with multiple dependent claims giving explicit concentration ranges.
Core requirement (broad)
- Claim 1: tyloxapol present in an amount sufficient to stabilize the first component.
This “sufficient to stabilize” language is broad and will often be litigated via stability testing and formulation science.
Dependent claims with explicit windows (more enforceable)
- Claim 5 / 15 / 27: tyloxapol 0.01–0.05 w/v %
- These are paired with specific active concentration ranges (e.g., sodium salt 0.01–0.2 w/v %, or 0.02–0.1 w/v %).
Design-around pressure point: A competitor may try to move outside those ranges, or remove tyloxapol and use another stabilizer system. Whether that avoids the broad “sufficient to stabilize” limitation depends on whether tyloxapol remains in the product.
What excipients are claimed as essential or allowed: “consists essentially of” and excipient lists
Short answer: The patent includes multiple “consists essentially of” configurations that lock in a defined excipient package, limiting permissible substitutions.
“Consists essentially of” formulations (key dependent claims)
Claim 9: stable aqueous liquid preparation consists essentially of:
- (a) active (2-amino-3-(4-bromobenzoyl)phenylacetic acid sodium salt)
- (d) sodium tetraborate
- (e) EDTA sodium salt
- (f) benzalkonium chloride
- (g) polyvinylpyrrolidone
- (h) sodium sulfite
with sodium salt concentration 0.02–0.1 w/v %
(Claim 9 does not expressly mention other constituents beyond this list within the excerpted claim text; the structure of “consists essentially of” constrains unlisted materials.)
Claim 18: “consists essentially of”:
- (a) active (free acid or salt/hydrate)
- (b) tyloxapol
- (c) boric acid
- (d) sodium tetraborate
- (e) EDTA sodium salt
- (f) benzalkonium chloride
- (g) polyvinylpyrrolidone
- (h) sodium sulfite
with active sodium salt concentration 0.02–0.1 w/v %.
Claim 25: “consists essentially of” similar list:
- active (free acid or salt/hydrate)
- tyloxapol
- boric acid
- sodium tetraborate
- EDTA sodium salt
- benzalkonium chloride
- polyvinylpyrrolidone
- sodium sulfite
with active sodium salt concentration 0.02–0.1 w/v %.
Quaternary ammonium salt option
- Claim 7: aqueous preparation further comprises a quaternary ammonium salt.
- Claim 17: same add-on in claim 11 scaffold.
This can broaden formulation variants if benzalkonium chloride already satisfies “quaternary ammonium,” but the claim language still leaves room for additional/alternative quaternary ammonium components depending on interpretation.
What stability and quality tests are required: >90% remaining after 60°C for 4 weeks and EP preservative efficacy
Short answer: Some claims add testable stability and preservative efficacy metrics that can be used to enforce product-specific boundaries.
Heat storage stability criteria
- Claim 11: stable liquid is characterized in that >90% of original first component remains after 60°C for 4 weeks.
- Claim 12: threshold tightens to >92% after the same stress condition.
- Claim 26: in claim 19 scaffold, >90% after 60°C for 4 weeks.
This is a direct “spec-driven” limitation.
EP-criteria B preservative efficacy standard
- Claims 28–30: the preparation further satisfies European Pharmacopoeia EP-criteria B:
- Bacteria:
- S. aureus, P. aeruginosa:
- 24 hours and 7 days post-inoculation:
- no more than 1/10 and 1/1000, respectively
- thereafter, counts level off or decrease
- Fungi:
- C. albicans, A. niger:
- 14 days post-inoculation:
- thereafter, counts keep the same level as at 14 days
Enforcement effect: Even if a competitor uses the same active and tyloxapol, failing EP preservative performance could defeat these dependent claims.
What is the mannitol exclusion: does US 8,927,606 cover “no mannitol” formulations?
Short answer: Yes. One independent claim variant explicitly requires that the ophthalmic liquid preparation does not include mannitol.
- Claim 19: stable aqueous ophthalmic preparation with tyloxapol and active, provided that the liquid preparation does not include mannitol.
This is a straightforward product design constraint for the claim 19-dependent family.
What are the practical concentration windows for infringement: tyloxapol and sodium salt ranges across dependent claims?
Short answer: Tyloxapol windows cluster around 0.01–0.05 w/v %, while the active sodium salt clusters around 0.02–0.1 w/v %, with one broader dependent range extending to 0.2 w/v %.
Concentration matrix by dependent claim cluster (from your claim text)
| Claim cluster |
Tyloxapol (w/v %) |
Active first component (sodium salt) (w/v %) |
Notes |
| Claim 5 |
0.01–0.05 |
0.01–0.2 |
Active is sole active |
| Claim 6 / 9 / 12? |
(paired in claim 5/15/27 families) |
0.02–0.1 |
Narrowed range |
| Claim 15 |
0.01–0.05 |
0.01–0.2 |
|
| Claim 16 |
(paired) |
0.02–0.1 |
|
| Claim 23 |
0.01–0.05 |
0.05–0.2 |
Broader upper bound |
| Claim 24 |
(paired) |
0.02–0.1 |
|
| Claim 27 |
0.01–0.05 |
0.02–0.1 |
|
| Claim 8 |
not specified in text |
about 0.1 |
“About” value |
Key risk for competitors: A narrow “sweet spot” exists where the formulation is explicitly within claim ranges; a close-range redesign may still land within “about” and test-and-interpretation outcomes.
How broad is the patent estate around this concept: what claim features likely determine infringement or non-infringement?
Short answer: The most decisive claim elements are:
- sole active limitation,
- tyloxapol presence (and stabilizing-effective amount),
- active identity including salt/hydrate forms,
- concentration windows,
- “consists essentially of” excipient package (where invoked),
- stability after 60°C/4 weeks (for the relevant families),
- EP-criteria B preservative efficacy (for the relevant families),
- mannitol absence (for the claim 19 family).
Competitive strategy implications
- If tyloxapol is replaced: independent claim 1’s “second component is tyloxapol” fails; design-around is based on removing tyloxapol entirely.
- If tyloxapol remains but concentrations change: dependent claims may be avoided, but independent claim 1 can still be asserted if tyloxapol is “sufficient to stabilize.”
- If “sole active” is violated by including an additional ophthalmic active: claims fail where sole-active is required (as stated).
- If stability specs are not met: claims 11/12/26 dependent limitations can block that asserted claim set.
- If mannitol is present: claim 19 family limitations can block.
What does US 8,927,606 cover vs not cover: formulation vs device vs combination therapy
Short answer: The patent is directed to ophthalmic liquid composition administration for inflammatory disease. It is not a device patent and is not written as a combination-therapy claim that allows additional actives.
Not covered (based on the claim text)
- Therapies where the preparation includes another pharmaceutical active besides the specified active (independent claim 1 explicitly requires sole active ingredient).
- Non-liquid ophthalmic dosage forms (claims specify “stable aqueous liquid preparation” formulated for ophthalmic administration).
- Products that include mannitol if the claim 19 limitation is asserted.
Covered
- A stable aqueous ophthalmic liquid with tyloxapol as stabilizer and the specified active in specified hydrate/salt form.
- Indications framed as ocular inflammation including postoperative inflammation.
Key takeaways on US 8,927,606 claim scope and infringement exposure
- The patent claims a composition-constrained method: ophthalmic treatment requires administering a tyloxapol-stabilized aqueous liquid where the active is the sole pharmaceutical active ingredient.
- Enforceability is layered: broad independent claim language exists, but multiple dependent claims add hard product specs:
- >90% (or >92%) remaining after 60°C for 4 weeks
- EP preservative efficacy EP-criteria B performance
- excipient package locks via “consists essentially of”
- no mannitol requirement for the claim 19 family
- The strongest practical “at-the-bottle” boundaries are:
- tyloxapol inclusion and level,
- active concentration ranges,
- salt/hydrate identity, and
- stability/preservative test outcomes.
FAQs
1) Does US 8,927,606 require a specific dosing regimen (e.g., twice daily)?
The claims require administering at a dose and frequency effective to treat the inflammatory disease, but they do not fix a specific regimen. Infringement still depends on the administered product meeting the formulation limitations.
2) Can the active be the free acid or only the sodium salt?
The independent claim 1 covers the free acid and salts/hydrates; dependent claim 4 and several dependent clusters specifically require the sodium salt.
3) Is mannitol allowed in all formulations covered?
Not in the claim 19 family: that independent claim variant states the liquid preparation does not include mannitol. Other independent/dependent paths do not include that exclusion in your provided claim text.
4) Is EP preservative efficacy part of the core claim?
It appears in dependent claims (28–30). If those dependent claims are asserted, the product must meet EP-criteria B.
5) If a competitor uses a different stabilizer than tyloxapol, does US 8,927,606 apply?
Based on the claim language you provided, the second component is specifically tyloxapol in the claimed methods. A different stabilizer would avoid the “second component is tyloxapol” limitation.
References
- United States Patent 8,927,606 (claims as provided in the prompt).
