United States Patent 8,946,281 (US8946281): Scope, Claim Set, and Ocular-Pain Ketorolac Landscape
US 8,946,281 claims a topical, ophthalmic method for treating ocular pain with a specific formulation of ketorolac tromethamine at 0.4% w/v (and dependent compositions with defined excipients) dosed at least once daily, with a proven comparative advantage over 0.5% w/v ketorolac tromethamine. The claim logic is concentration-first (0.4% vs 0.5%) plus outcome metrics tied to ocular comfort and side effects (stinging/foreign body sensation), followed by optional narrowing to dosing frequency, surgery context, and specific formulation components.
What is the core independent claim scope (Claim 1)?
Claim 1 (independent) recites a method of treating ocular pain in a person via administering at least once daily to an eye a first ophthalmic composition comprising:
- Ketorolac tromethamine: about 0.4% w/v
- Treatment outcome: reduces ocular pain
- Comparative safety/comfort: less ocular side effects than a second composition comprising 0.5% w/v ketorolac tromethamine
- Side effect definition: at least one side effect selected from stinging and foreign body sensation
Practical meaning
For infringement risk and freedom-to-operate (FTO), Claim 1 is not limited to a particular indication label beyond “ocular pain.” It is defined by:
- Dose regimen: at least once daily
- API concentration: 0.4% w/v ketorolac tromethamine
- Comparator: method requires a comparative relationship versus 0.5% w/v ketorolac
- Clinical endpoints: ocular pain reduction plus reduced stinging/foreign body sensation
Claim 1 trigger conditions
A product or study regimen that matches all of the following would fall within the literal structure of Claim 1:
- Topical ocular administration
- At least once daily dosing
- Ketorolac tromethamine at about 0.4% w/v in the administered formulation
- A resulting reduction in ocular pain
- Reduced stinging and/or foreign body sensation compared to a 0.5% w/v ketorolac regimen
How do dependent claims narrow the scope?
Dependent claims add formulation detail and specific use contexts, tightening the claim set around commercial formulation designs.
Dosing frequency
- Claim 2: first composition is administered four times daily.
This narrows Claim 1 to a q.i.d. regimen (a common post-op dosing pattern).
Outcome superiority framed as “increased ocular comfort”
- Claims 3 and 4: increased ocular comfort versus the 0.5% comparator.
- Claim 4 further ties this to Claim 2 (q.i.d.).
Comparable efficacy at lower concentration
- Claim 5: the 0.4% composition is as effective as the 0.5% composition in treating ocular pain despite lower concentration.
This reinforces a “concentration reduction with maintained analgesia” theme and can matter in proof and enforcement posture.
Administration mode
- Claim 6: administration is by topical instillation.
This excludes non-instillation routes for ocular delivery (though most ophthalmic ketorolac products are instilled).
Specific excipients (formulation-specific claims)
- Claim 7: composition comprises edetate disodium.
- Claim 13: 0.4% ketorolac tromethamine and about 0.006% benzalkonium chloride.
- Claim 14: 0.4% ketorolac + 0.006% benzalkonium chloride + 0.015% edetate disodium.
- Claim 15: adds 0.003% octoxynol 40 to Claim 14 components.
- Claim 16: adds water to Claim 15.
- Claim 17: adds hydrochloric acid and sodium hydroxide to adjust pH to about 7.4 (with the rest of Claim 16 components).
Ocular pain etiology and surgical context
- Claim 8: person is experiencing ocular pain due to corneal refractive surgery.
- Claims 10 and 11: method reduces pain and ocular stinging after ophthalmic surgery, where Claim 11 specifies corneal refractive surgery.
- Claim 12: method reduces ocular burning after ophthalmic surgery.
Mechanism framing
- Claim 9: method results in analgesic activity to the patient’s eye.
While “analgesic activity” overlaps with pain reduction, it provides an additional proof hook.
What is the effective “formulation matrix” that the claims cover?
Claim 1 covers “at least once daily” dosing with 0.4% w/v ketorolac tromethamine, then the dependent claims map out additional excipient and pH configurations.
Below is a structured mapping of the claim-defined formulations:
| Claim |
Ketorolac tromethamine |
Benzalkonium chloride |
Edetate disodium |
Octoxynol 40 |
Water |
pH target |
| 1 |
~0.4% w/v |
Not required |
Not required |
Not required |
Not required |
Not required |
| 2 |
Same as Claim 1 |
Not required |
Not required |
Not required |
Not required |
Not required |
| 13 |
~0.4% w/v |
~0.006% w/v |
Not required |
Not required |
Not required |
Not required |
| 14 |
~0.4% w/v |
~0.006% w/v |
~0.015% w/v |
Not required |
Not required |
Not required |
| 15 |
~0.4% w/v |
~0.006% w/v |
~0.015% w/v |
~0.003% w/v |
Not required |
Not required |
| 16 |
~0.4% w/v |
~0.006% w/v |
~0.015% w/v |
~0.003% w/v |
Water included |
Not required |
| 17 |
~0.4% w/v |
~0.006% w/v |
~0.015% w/v |
~0.003% w/v |
Water included |
~7.4 adjusted using HCl/NaOH |
Excipients are not required for Claim 1, but they become required in the dependent sub-set of the claim chain. This structure means enforcement can occur broadly on concentration-based method scope (Claim 1), while also allowing narrower formulation-specific claims (Claims 13-17).
Where is the claim set most likely to bite competitors?
Most direct competitive landing zone
- A generic or follow-on product that targets ocular pain with ketorolac tromethamine at ~0.4% w/v and includes the usual instillation schedule is positioned close to Claim 1.
- The comparator relationship in Claim 1 (0.5% vs 0.4%) means that, in practice, the patentee can frame comparative safety and comfort relative to higher concentration ketorolac.
Formulation-specific landing zone
If a competitor uses the same excipient system and pH:
- benzalkonium chloride at about 0.006% w/v
- edetate disodium at about 0.015% w/v
- octoxynol 40 at about 0.003% w/v
- water and pH adjusted to about 7.4
then the product aligns with dependent claims 13-17.
Clinical-use landing zone
If the labeling and patient population focus on post-op ocular pain and stinging, especially corneal refractive surgery:
- Claims 8, 10, 11, 12 become relevant to claim mapping.
- Even without explicit label language, evidence of the prescribed use pattern can be used to tie administration to the claim’s patient scenario.
How the claims structure interacts with obvious design-arounds
The patent does not claim a broad “any lower concentration of ketorolac” rule. It anchors on a specific concentration and comparative safety framing. Design-around feasibility depends on whether a challenger can avoid at least one required feature of Claim 1.
Likely avoidance levers
- Move away from ~0.4% w/v ketorolac tromethamine: avoid literal match on the concentration requirement.
- Avoid the comparative endpoint framing: Claim 1 is explicitly tied to reduced stinging/foreign body sensation versus 0.5% ketorolac. A product without evidence of that comparative reduction could be less compatible with the claim’s proof requirements.
- Change excipient system: this targets dependent claims (13-17) more directly than Claim 1.
Less certain levers
- Changing dosing frequency: only Claim 2 and 4 require q.i.d.; Claim 1 covers at least once daily.
- Changing surgical context: Claim 1 covers ocular pain generally; surgical context is not required unless asserting dependent claims.
US patent landscape: how this claim set typically sits relative to ketorolac ophthalmics
This patent is a concentration-and-comfort-driven method patent tied to topical ketorolac tromethamine. In the broader ketorolac ophthalmic landscape, several common pillars recur:
- Concentration variants of ketorolac (lower vs higher) and their tolerability profiles (stinging/foreign body sensation are classic tolerability endpoints).
- Topical dosing regimens (often once daily to q.i.d., especially post-op).
- Excipients and pH adjustments used to stabilize the formulation and manage tolerability.
US 8,946,281 differentiates itself by making 0.4% w/v the first composition and 0.5% w/v the explicit comparator, with stinging/foreign body sensation as the safety discriminator and ocular comfort/pain reduction as the efficacy tie.
Claim scope summary for enforcement and FTO
Coverage highlights
- Topical ocular pain treatment
- At least once daily dosing
- Ketorolac tromethamine at about 0.4% w/v
- Comparative reduced ocular side effects versus 0.5% w/v
- Side effects include stinging and foreign body sensation
- Dependent narrowing to:
- q.i.d. dosing
- increased ocular comfort
- equivalently effective analgesia at lower concentration
- instillation delivery
- specific excipient combinations and pH adjustment
- corneal refractive surgery pain/stinging/burning
High-sensitivity elements (literal mapping)
- “about 0.4% w/v ketorolac tromethamine”
- “at least once daily”
- “less ocular side effects” including “stinging” and/or “foreign body sensation” versus “0.5% w/v ketorolac tromethamine”
- Topical instillation (if dependent claim 6 is asserted)
- Specific excipients/pH (if dependent claims 13-17 are asserted)
Key Takeaways
- US 8,946,281 is anchored on a concentration-specific method: topical ocular instillation with about 0.4% w/v ketorolac tromethamine dosed at least once daily, with demonstrated reduced stinging and/or foreign body sensation versus a 0.5% w/v comparator.
- Dependent claims materially narrow to q.i.d. dosing, ocular comfort superiority, and specific excipient sets (benzalkonium chloride ~0.006%, edetate disodium ~0.015%, octoxynol 40 ~0.003%) with pH about 7.4.
- Corneal refractive surgery post-op pain is a clear clinical framing for dependent coverage (stinging and burning).
FAQs
1) Does Claim 1 require benzalkonium chloride or edetate disodium?
No. Claim 1 requires only about 0.4% w/v ketorolac tromethamine and the comparative clinical outcome structure.
2) Is q.i.d. dosing mandatory for infringement of the independent claim?
No. Claim 2 adds q.i.d. as a dependent limitation. Claim 1 requires only at least once daily.
3) Can a different ketorolac concentration avoid the patent?
If it is not “about 0.4% w/v,” it avoids the literal concentration limitation of Claim 1; the claim set does not read on concentrations other than the defined first composition.
4) What excipients are explicitly tied to dependent formulation claims?
Benzalkonium chloride (~0.006%), edetate disodium (~0.015%), octoxynol 40 (~0.003%), and pH adjustment to about 7.4 (via HCl/NaOH), with water.
5) Is corneal refractive surgery required?
No. Corneal refractive surgery appears in dependent claims (not required for Claim 1).
References
[1] US Patent Application Publication / Patent: US 8,946,281 (United States) (claims as provided in the prompt).
