US Patent 9,066,856 (Phenylephrine + Ketorolac Sterile Liquid Formulation): Scope, Claim Map, and US Patent Landscape
US 9,066,856 claims a preservative-free, antioxidant-free sterile aqueous liquid formulation containing phenylephrine plus ketorolac with a sodium citrate buffer, specified pH, and stability targets at 5±3°C to 25±2°C, including single-use-container packaging and concentration and ratio ranges. The claim set is tightly focused on (i) combination actives, (ii) buffer chemistry and pH band, (iii) demonstrated shelf-life under real-world storage windows, and (iv) compatibility with irrigation-carrier injection where post-injection concentrations fall within defined windows.
What does US 9,066,856 claim protect for phenylephrine plus ketorolac sterile liquid formulations?
Executive take: core protected elements
US 9,066,856 protection centers on an aqueous, sterile liquid formulation with three coupled constraints:
- Composition: phenylephrine + ketorolac in an aqueous carrier with a buffer system
- Buffer and pH: sodium citrate buffer and pH 5.8 to 6.8
- Stability and packaging: stability ≥6 months (and dependent claim ≥24 months) at 5±3°C to 25±2°C, in single-use container, and in claims 9-16 specifically stable in absence of preservatives and antioxidants
Claim set structure (independent + dependent)
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Claim 1 is the primary independent claim. It covers a sterile liquid formulation of:
- phenylephrine + ketorolac
- buffer system in aqueous carrier
- stable ≥6 months at 5±3°C to 25±2°C
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Claims 2-8 add:
- sodium citrate buffer (claim 2)
- pH band 5.8-6.8 (claim 3)
- stability ≥24 months (claim 4)
- single-use container (claim 5)
- specific concentrations ~60.75 mM phenylephrine and ~11.25 mM ketorolac (claim 6)
- irrigation-carrier injection compatibility with defined post-injection concentrations (claim 7)
- molar ratio 3:1 to 10:1 (claim 8)
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Claims 9-16 provide a second cluster that is substantially parallel to claims 1-8 but adds the “in the absence of preservatives and antioxidants” requirement, then repeats buffer/pH, stability, container, and concentration/ratio/injection constraints:
- claim 9: sterile liquid phenylephrine + ketorolac + buffer, stable ≥6 months at 5±3°C to 25±2°C without preservatives and antioxidants
- claims 10-16: sodium citrate, pH, ≥24 months, single-use container, specific concentrations, post-injection concentration windows, and ratio band
What is actually “essential” to infringement risk
Because the claims are composition-and-stability claims with narrow parameters, infringement risk is strongest where a product:
- is sterile and liquid
- uses the same actives combination (phenylephrine + ketorolac)
- uses a buffer system that includes sodium citrate (claims 2/10) and fits the pH band 5.8-6.8 (claims 3/11)
- meets stability requirements (claims 1/9 for ≥6 months; claims 4/12 for ≥24 months)
- is preservative-free and antioxidant-free (claims 9-16)
- is in single-use containers (claims 5/13)
- matches concentration and ratio ranges (claims 6-8 and 14-16)
- matches injection scenario post-injection concentrations within windows (claims 7 and 15)
The patent’s novelty position is the combination of these constraints, not merely “phenylephrine + ketorolac” alone.
How broad are the concentration, ratio, and pH limitations in US 9,066,856?
pH band: 5.8 to 6.8
This band is a key “fence”:
- If a generic or alternative buffer yields a formulation outside 5.8-6.8, it can avoid dependent claims 3/11.
- Note that claim 1 does not expressly recite the pH band; claim 3/11 do. For infringement analysis, look at claim hierarchy: claim 1 can still be asserted if the product meets the buffer and stability elements even when pH falls outside 5.8-6.8, but the narrowest commercial designs typically target the dependent claims because they align with the strongest patentability narrative.
Sodium citrate buffer system: explicit in dependent claims
Claims 2 and 10 explicitly require sodium citrate buffer.
- A competing formulation using a different buffer (eg, phosphate or borate) may aim to avoid those dependent claims.
- However, claim 1 and claim 9 only require “buffer system in an aqueous carrier,” which can still capture alternative buffers if stability is shown.
Phenylephrine and ketorolac numeric ranges
The patent uses both point concentrations and post-injection windows.
Fixed pre-injection concentrations (claims 6 and 14):
- phenylephrine about 60.75 mM
- ketorolac about 11.25 mM
Post-injection concentrations (claims 7 and 15):
- phenylephrine:
- claim 7: 240 to 72 μM (note the ordering suggests a lower-to-higher issue in the written range; interpret as 72 to 240 μM for practical analysis)
- claim 15: 240 to 720 μM
- ketorolac:
- claim 7: 10 to 270 μM
- claim 15: 10 to 270 μM (same)
Molar ratio (claims 8 and 16):
- phenylephrine:ketorolac 3:1 to 10:1
Practical scope observation
- Designs that land at or near 60.75 mM / 11.25 mM naturally fall into a ratio range:
- 60.75 / 11.25 = ~5.4:1, which is within 3:1 to 10:1.
- If a competitor deviates meaningfully (eg, ratio <3:1 or >10:1), it can avoid dependent claims 8/16, but not necessarily claim 1/9 if other elements match.
What does the “stable for at least 6 months/24 months” language mean for claim validity and infringement?
Storage window is explicit
- 6-month stability is required at 5±3°C to 25±2°C (claims 1 and 9).
- 24-month stability at 5±3°C to 25±2°C is required in dependent claims (claims 4 and 12).
How stability claims are typically litigated
For litigation leverage:
- The patent holder will argue that stability is an inherent property when the formulation parameters are met.
- The accused infringer will argue:
- failure to meet the required stability endpoint under those conditions
- differences in manufacturing process that affect degradation kinetics
- differences in fill/closure system that alter oxygen/water activity
Where “stable” is a key design constraint
If a generic company proposes:
- a different buffer system,
- a different antioxidant/preservative profile,
- different concentrations that still keep pH near target,
the main remaining question is whether it survives the same stability criteria. The patent is drafted to lock that performance into the claim, making testing data central.
Which parts of the claim set are most important for US litigation strategy?
Strongest claim “clusters” for enforcement
- Preservative-free and antioxidant-free (claims 9-16)
- This is a high-value feature because many sterile formulations use either preservatives, antioxidants, or both. A product that has either can attempt to avoid these dependent claims directly.
- Sodium citrate + pH band (claims 10 and 11)
- These narrow the formulation chemistry and create a clean off-ramp for alternate buffering.
- Concentration/ratio windows + irrigation scenario (claims 7 and 15 + claims 8 and 16)
- These parameters create a second orthogonal fence beyond chemistry.
What is the “claim ladder” coverage logic?
- Claims 1 and 9 are broader on pH and buffer identity.
- Dependent claims narrow:
- to sodium citrate and pH
- to stability ≥24 months
- to single-use container
- to exact concentration and injection outcomes
- to preservative/antioxidant-free status in the second cluster
In practice, litigation generally asserts a set of:
- independent claim plus multiple dependents that match the accused product’s specific design.
What formulation alternatives could avoid dependent claims while still using phenylephrine and ketorolac?
Avoiding sodium citrate + pH band (dependent claims)
- Use a different buffer system and/or adjust pH to outside 5.8-6.8.
- Risk: claim 1/9 still requires only a buffer system plus stability, so avoidance is partial unless stability also differs.
Avoiding preservative-free and antioxidant-free (dependent claims 9-16)
- If the product contains preservatives and/or antioxidants, it can avoid claims 9-16.
- Risk: claim 1/4 might still be asserted (not requiring preservative/antioxidant-free language).
Avoiding concentration and ratio dependencies
- Adjust pre-injection concentrations so that:
- phenylephrine is not about 60.75 mM
- the phenylephrine:ketorolac molar ratio falls outside 3:1 to 10:1
- Adjust irrigation-carrier injection dilution so post-injection phenylephrine/ketorolac do not fall within the windows.
Risk: even if these dependents are avoided, the independent claims remain if:
- the buffer system and stability are met.
How does “single-use container” change the product liability and design-around space?
Single-use container language appears in:
This creates a packaging-dependent fence:
- If a competitor uses multi-dose containers with preservatives or different closure strategies, it can avoid these dependents.
- But again, claim 1/9 do not require single-use, so packaging avoidance does not fully neutralize infringement exposure.
How many related US patents typically surround a combination sterile formulation like this?
Without a provided family list and without the prosecution record, no complete, accurate count can be produced. The correct scope-limiting statement is that US 9,066,856’s claim set itself is formulation-focused and does not show method-of-use or device claims in the claim text provided.
For business decisions, treat US 9,066,856 as:
- a formulation IP anchor for preservative-free, sodium citrate buffered, phenylephrine + ketorolac sterile liquid compositions with defined stability and injection outcome ranges.
If you are mapping competitor risk, the next layer is usually:
- related continuation patents on stability, process, alternative buffers, or container systems, plus
- formulation patents covering specific dilution steps and irrigation compatibility.
No other numbered US patents can be enumerated from the information provided.
What is the Orange Book status of US 9,066,856?
No mapping to an FDA NDA/ANDA Orange Book listing is possible from the information provided. A determination of Orange Book status requires the drug product and strength, and linkage to patent numbers listed for an approved application.
What patent expiration and exclusivity timelines apply to US 9,066,856?
No expiration date or PTA/PTE adjustments can be computed from the information provided. US patent term depends on:
- the earliest non-provisional filing date,
- any patent term adjustment,
- any patent term extension.
The claim text alone does not provide those inputs.
Which generic entry risks exist for phenylephrine + ketorolac sterile liquids?
Key risk drivers
- High likelihood that FDA-application amendments for sterile ophthalmic or surgical irrigation products require reformulation testing.
- Stability and preservative/antioxidant status are technical gating items.
- If the commercial product is preservative-free/antioxidant-free, it aligns with claims 9-16 and increases risk.
Key safe harbors for generic entrants
- Formulate with preservatives and/or antioxidants to avoid claims 9-16.
- Use a non-sodium citrate buffer and/or adjust pH outside 5.8-6.8 to avoid claims 2/3 and 10/11.
- Alter concentration and post-injection dilution profile such that the post-injection concentration windows and ratio bands are not met.
Because claim 1/9 are still broadly framed around “buffer system” and stability, generic safe harbor requires meeting the full set of differences, not a single element shift.
Key Takeaways
- US 9,066,856 protects a sterile aqueous liquid combining phenylephrine + ketorolac with a buffer system, anchored by stability at 5±3°C to 25±2°C (≥6 months) and, in dependents, ≥24 months.
- The highest-value dependent fences are sodium citrate buffer, pH 5.8-6.8, single-use container, and in claims 9-16, explicit preservative-free and antioxidant-free status.
- The claim set adds numerical composition constraints (about 60.75 mM phenylephrine and 11.25 mM ketorolac) plus molar ratio 3:1 to 10:1 and irrigation post-injection concentration windows, creating multiple design-arounds but also multiple technical tests for entrants.
- From an enforcement standpoint, the most litigation-relevant cluster is claims 9-16 because they align to preservative-free ophthalmic/surgical sterile products that match a common commercial niche.
FAQs
1) Does US 9,066,856 require sodium citrate?
Only the dependent claims (claims 2 and 10) explicitly require sodium citrate buffer. The independent claims require a buffer system generally.
2) Can a product infringe claim 1 if pH is outside 5.8 to 6.8?
Claim 1 does not expressly require the pH band; pH 5.8 to 6.8 is required in claim 3 (and claim 11 for the preservative-free cluster).
3) What does “absence of preservatives and antioxidants” practically do to infringement scope?
It narrows claims 9-16 to products that contain neither preservatives nor antioxidants. Any inclusion of either can avoid those dependent claims, but claim 1/4 may still be asserted depending on the product match.
4) Are concentration ranges tied to pre-injection or post-injection conditions?
Both. Claims 6/14 give pre-injection concentrations. Claims 7/15 give post-injection concentrations after injection into an irrigation carrier.
5) Does single-use packaging matter for claim coverage?
It matters for dependent claims 5 and 13. Independent claims are not restricted to single-use based solely on the text provided.
References
- United States Patent 9,066,856.
