US RE49422: Scope, Claim-by-Claim Read, and US Patent Landscape for Low-Concentration, Preservative-Free Injectable Noradrenaline Solutions
What is RE49422 and what does it cover?
US RE49422 is a reissue directed to a stable injectable noradrenaline (or noradrenaline salts, including bitartrate) solution at low concentration, formulated with degassed water, NaCl, and HCl to set pH 3.3 to 3.6, under substantially oxygen-free handling, with defined degradation/impurity endpoints and explicit formulation restrictions: free of preservatives and anti-oxidizing agents (and in narrower embodiments, free of complexing agents).
The claim set is structured around three core technical pillars:
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Formulation window
- Noradrenaline base (or salt expressed as noradrenaline base) at 0.04 to 0.2 mg/mL in the main solution claims; and ≤0.2 mg/mL in alternative solution claims; plus a container claim with <1 mg/mL.
- Solvent is degassed/deaerated water.
- Excipient is NaCl.
- Hydrochloric acid to achieve pH 3.3–3.6.
- Preservative-free and anti-oxidizing agent-free (and in some claims also complexing agent-free).
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Oxygen control
- Solvent oxygen ≤100 ppb is recited in multiple dependent claims.
- Method/container claims require processing “in substantial absence of air or oxygen” and include inert-gas current processing steps.
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Stability/impurity specifications
- After 6 months at 25°C, composition includes:
- <0.2% arterenone
- <0.5% impurities other than arterenone
- <10% d-noradrenaline
- These endpoints appear across solution and process-dependent variants, anchoring patentability to stability performance, not just composition.
Claim 1: What is the core independent composition claim?
Claim 1 covers a stable injectable noradrenaline solution with these limitations:
- Drug: noradrenaline
- Concentration: 0.04 to 0.2 mg/mL
- Solvent: degassed/deaerated water
- Excipient: NaCl
- Acid/pH: hydrochloric acid, pH 3.3 to 3.6
- Additives excluded: free of preservatives and anti-oxidizing agents
Scope characterisation
- This is a tight composition claim: narrow concentration band plus specific excipient and pH.
- It is silent on oxygen level of the solvent itself in Claim 1 (it is required to be degassed/deaerated, but not quantified here).
- It is also silent on sterility/terminal sterilization mode, leaving those to dependent/process claims.
Claim 2: How does the independent process dimension narrow it?
Claim 2 depends on Claim 1 (process steps for making the Claim 1 composition), adding a method sequence:
a. Dissolve noradrenaline and NaCl in deoxygenated/degassed water to 0.04–0.20 mg/mL
b. Adjust with HCl to pH 3.3–3.6
c. Filtrate the solution in an inert gas current
d. Distribute the solution in an inert gas current
e. Sterilize the noradrenaline solution
Scope characterisation
- Claim 2 ties stability to oxygen-minimizing manufacturing logistics (inert gas current during filtration and distribution).
- It does not specify whether sterilization is filtration-based or heat-based in Claim 2 itself; later dependent claims do.
Claim 3: What oxygen specification is explicitly claimed?
Claim 3 adds:
Scope characterisation
- This converts “degassed/deaerated” into a quantified oxygen metric, constraining infringement for products that may be degassed but not to ≤100 ppb.
Claim 4: How is the second independent composition claim structured?
Claim 4 is another independent composition claim, but broadened/shifted in drug salt framing:
- Drug: noradrenaline or pharmaceutically acceptable salt
- Concentration: concentration of drug based on noradrenaline base ≤0.2 mg/mL
- Solvent: degassed/deaerated water
- Excipient: NaCl
- pH: 3.3–3.6 (via HCl)
- Excluded: preservatives and anti-oxidizing agents
- Also excluded (additional restriction): complexing agents
Scope characterisation
- Claim 4 is broader than Claim 1 in concentration upper bound (≤0.2 rather than 0.04–0.2), while also adding a negative formulation restriction: complexing agents are excluded.
Claim 5: What does the container-/process packaging claim add?
Claim 5 is process-by-product-ish: it specifies the solution in one or more sealed containers, and adds a more detailed manufacturing method:
a. Dissolve noradrenaline or salt and NaCl in deoxygenated/degassed water to give concentration ≤0.2 mg/mL (expressed as noradrenaline base)
b. Adjust with HCl to pH 3.3–3.6
c. Filtrate in an inert gas current
d. Distribute in inert gas current into sealed containers
e. Sterilize, where sterilizing comprises filtrating (optionally during step c) and/or heat sterilizing
Scope characterisation
- This claim includes packaging constraints (sealed containers) and flexible sterilization routes (filtration and/or heat).
- It can read on products with different terminal sterilization strategies as long as the inert gas current filtration/distribution is used and the formulation meets the composition restrictions.
Claim 6 and 9: What other oxygen constraint appears?
- Claim 6: solvent oxygen ≤100 ppb (dependent on Claim 4)
- Claim 9: solvent oxygen ≤100 ppb (dependent on Claim 5)
Scope characterisation
- These reinforce that oxygen quantification is a meaningful axis for narrowing.
Claims 7, 10, 11, 15, 18, 19: What stability metrics are required after storage?
Multiple dependent claims repeat the same 6-month stability profile. Examples:
- Claim 7 (dependent on Claim 4): after 6 months at 25°C
- <0.2% arterenone
- <0.5% impurities other than arterenone
- <10% d-noradrenaline
- Claim 10 and Claim 11 replicate similar endpoints across Claim 4/5/6 variants.
- Claim 15 repeats endpoints for the Claim 12 family.
- Claims 18 and 19 repeat endpoints for the Claim 13 family (with and without oxygen ≤100 ppb dependency).
Scope characterisation
- These are performance limitations that can be decisive in infringement if an accused product has different degradation/epimerization outcomes.
Claims 8 and 16: What sterilization variant is captured?
- Claim 8 (dependent on Claim 5): sterilizing comprises filtrating during step (c).
- Claim 16 (dependent on Claim 13): similar approach, sterilizing comprises filtrating during step (c).
Scope characterisation
- These are narrower sterilization-positioning constraints.
Claims 12 and 13: How does noradrenaline bitartrate change the claim?
Claim 12 (independent composition) specifies:
- Drug: noradrenaline or pharmaceutically acceptable salt, but explicitly includes noradrenaline bitartrate concentration framing
- Concentration: noradrenaline bitartrate ≤0.2 mg/mL based on noradrenaline base
- Solvent: degassed/deaerated water
- Excipient: NaCl
- pH: 3.3–3.6
- Excluded: preservatives, anti-oxidizing agents
Claim 13 is the corresponding process + sealed containers claim:
- Dissolve noradrenaline bitartrate + NaCl in deoxygenated/degassed water at ≤0.2 mg/mL (expressed as noradrenaline base)
- Adjust with HCl to pH 3.3–3.6
- Filtrate in inert gas
- Distribute in inert gas into sealed containers
- Sterilize using filtrating (optionally during step c) or heat sterilizing
Scope characterisation
- The bitartrate set mirrors the free-base/salt set but makes the salt form explicit in the concentration and stoichiometric framing.
Claims 14 and 17: Oxygen ≤100 ppb for bitartrate family
- Claim 14: solvent oxygen ≤100 ppb (dependent on Claim 12)
- Claim 17: solvent oxygen ≤100 ppb (dependent on Claim 13)
Claim 20: What is the broader container claim with <1 mg/mL?
Claim 20 covers:
- Container of low concentration injectable noradrenaline bitartrate
- Concentration: <1 mg/mL based on noradrenaline base
- Produced by method steps in substantial absence of air or oxygen:
a. Dissolve noradrenaline bitartrate in degassed/deoxygenated water to <1 mg/mL
b. Adjust with HCl to pH 3.3–3.6
c. Filtrate in inert gas current
d. Distribute into one or more containers in inert gas current
e. Sterilize, where sterilizing comprises filtrating (optionally during step c) or heat sterilizing
- After 6 months at 25°C:
- <0.2% arterenone
- <0.5% impurities other than arterenone
- <10% d-noradrenaline
- Explicitly: solution is free of preservatives and anti-oxidizing agents
Scope characterisation
- This is the largest numeric window on strength: it goes up to just under 1 mg/mL.
- It is still anchored to the same oxygen-minimizing handling and same stability endpoints.
Claims 21–23: Narrowing sub-variants of Claim 20
- Claim 21: sterilizing comprises filtrating during step (c)
- Claim 22: solution is preservative-free, antioxidant-free, and free of complexing agents
- Claim 23: concentration ≤0.2 mg/mL (tighter subset of Claim 20)
How the claim set maps to product infringement risk
“Core essentials” most likely to be directly read by an accused injectable
- Noradrenaline (or bitartrate/salt) in aqueous NaCl
- HCl to pH 3.3–3.6
- Degassed/deaerated water and oxygen-minimizing handling (inert gas during filtration/distribution)
- Preservative-free and antioxidant-free
- Matching concentration window:
- 0.04–0.2 mg/mL (Claim 1)
- ≤0.2 mg/mL (Claims 4/12/13/23)
- <1 mg/mL (Claim 20)
“Performance-anchored” limitations that can differentiate prior art vs infringement
- 6-month at 25°C limits:
- arterenone <0.2%
- other impurities <0.5%
- d-noradrenaline <10%
“Quantified oxygen” limitations
- solvent oxygen ≤100 ppb (Claims 3, 6, 9, 14, 17)
“Negative formulation” exclusions
- complexing agents excluded (Claim 4, Claim 22)
Patent landscape in the US: what to look for around RE49422 (scope-relevant competitor zones)
A full landscape requires the patent bibliographic record for US RE49422 and its full family and prosecution history. That record is not provided here, so the analysis below is limited to claim-scope adjacency zones that determine whether other filings are likely to be blocking, non-blocking, or clearly distinguishable.
1) Formulation patents on noradrenaline injections
Likely focal points in competing US filings
- Noradrenaline concentration in the sub-mg/mL to low-mg/mL range
- pH control near 3.3–3.6 using HCl
- use of NaCl (or alternatives)
- inclusion vs exclusion of:
- preservatives (e.g., parabens, antioxidants)
- complexing agents (where relevant)
- oxygen control strategy:
- degassed water only vs quantified oxygen (≤100 ppb)
- inert-gas processing during filtration/fill
How RE49422 differentiates
- It combines low concentration + specific excipient + pH window + explicit antioxidant/preservative exclusion + inert processing + defined stability endpoints.
2) Process patents on low-oxygen manufacturing and inert-fill
Likely competing angles
- inert atmosphere during filtration and/or filling
- degassing methods and quantification (oxygen ppb)
- sterilization approach (filtration vs heat)
- packaging sealed containers under oxygen-limited headspace
How RE49422 differentiates
- It recites inert gas current during filtrating and distributing and ties the resulting product to defined degradation/epimerization metrics.
3) Stability/impurity profile patents
Likely focal points
- suppression of:
- arterenone
- “other impurities”
- d-noradrenaline
- specifying:
- testing duration and temperature (here 6 months at 25°C)
- analytical definitions and percent limits
How RE49422 differentiates
- The claim set embeds explicit thresholds for three impurity categories after a specific storage condition.
4) Salt-form patents (bitartrate vs free base)
Likely focal points
- noradrenaline bitartrate vs noradrenaline base salts
- concentration expressed on a “noradrenaline base equivalent” basis
- formulation differences that can move the product across:
- ≤0.2 mg/mL vs <1 mg/mL vs 0.04–0.2 mg/mL
How RE49422 differentiates
- The bitartrate claims use the “based on noradrenaline base” framing and retain the same stability anchors.
Practical claim-to-product mapping for diligence
If a product targets sub-0.2 mg/mL noradrenaline injection
- Claims most directly implicated:
- Claim 1 (0.04–0.2 mg/mL, no preservatives/antioxidants)
- Claim 4 (≤0.2 mg/mL, complexing agent-free)
- Claim 12/Claim 13 (bitartrate ≤0.2 mg/mL family)
- oxygen-quantified dependencies: Claims 3, 6, 9, 14, 17
- Key differentiators to analyze:
- oxygen measured in solvent (≤100 ppb vs merely degassed)
- inclusion of complexing agents (Claim 4 and Claim 22)
- whether the manufacturing uses inert gas during filtration and distribution
- whether stability matches the <0.2%/ <0.5%/ <10% profiles after 6 months at 25°C
If a product is <1 mg/mL noradrenaline bitartrate injection
- Main exposure:
- Key differentiators:
- “substantial absence of air or oxygen” in method
- inert gas current during filtration and distribution
- stability thresholds after 6 months at 25°C
- preservative/antioxidant-free status
Key Takeaways
- RE49422’s claim scope is anchored on a low-dose injectable noradrenaline (including bitartrate) solution with NaCl, HCl-adjusted pH 3.3–3.6, degassed water, no preservatives/no antioxidants, plus inert-gas filtration/fill and 6-month at 25°C impurity thresholds (<0.2% arterenone; <0.5% other impurities; <10% d-noradrenaline).
- Numeric strength windows define the main infringement gates:
- 0.04–0.2 mg/mL (Claim 1)
- ≤0.2 mg/mL (Claims 4/12 and associated process/container claims)
- <1 mg/mL for bitartrate containers (Claim 20).
- Oxygen and formulation exclusions create separate narrowing axes:
- solvent oxygen ≤100 ppb
- complexing agent-free embodiments.
- Landscape implication: US competitors are most at risk if their products match both the formulation envelope and the manufacturing oxygen-control + stability endpoint combination.
FAQs
1) Which claims are the closest “composition-of-matter” anchors?
Claim 1 for noradrenaline base at 0.04–0.2 mg/mL; Claims 4 and 12 for ≤0.2 mg/mL formulations (salt/framing differences) with preservatives/antioxidants excluded.
2) What is the most important processing limitation in the method claims?
Inert-gas current handling during filtration and distribution (Claims 2 and 5/ 13 and inert-fill steps in 20).
3) Do the claims require a specific sterilization type?
Sterilization is generally required, while the narrower dependencies specify filtration during the inert-gas step (Claims 8, 16, 21). Other claims permit filtration and/or heat sterilization (e.g., Claim 5, Claim 13, and Claim 20).
4) What stability data is claimed?
After 6 months at 25°C, limits for arterenone (<0.2%), other impurities (<0.5%), and d-noradrenaline (<10%) recur across multiple dependent claims and in Claim 20.
5) How does the oxygen ≤100 ppb limitation affect scope?
It appears in dependent claims (Claims 3, 6, 9, 14, 17). Products that do not meet quantified oxygen can fall outside those specific dependencies, but still face broader infringement risks via inert-gas handling and “degassed/deaerated” requirements.
References
No sources were provided with the patent record or any external documents for US RE49422.
