IP Verse

Epinephrine Compositions And Containers

Patent No. US11071719 (titled "Epinephrine Compositions And Containers") was filed by Novaquest Co-Investment Fund X Lp on Feb 12, 2020.

What is this patent about?

’719 is related to the field of pharmaceutical compositions , specifically addressing the problem of stabilizing epinephrine in ready-to-administer injectable solutions. Epinephrine, a crucial drug for treating anaphylaxis and other emergencies, is known to degrade rapidly in aqueous solutions due to oxidation, racemization, and other factors. Existing formulations often require dilution prior to use, increasing the risk of dosage errors and contamination, or rely on antioxidants that can cause allergic reactions.

The underlying idea behind ’719 is to create a stable, ready-to-inject epinephrine formulation that overcomes the limitations of prior art by carefully controlling several key parameters. The formulation is antioxidant-free to avoid allergic reactions, uses a low concentration of epinephrine to eliminate the need for dilution, maintains a specific pH range of 3.0–4.7 for optimal stability, and incorporates a metal ion chelator to minimize degradation caused by metal ions. Dissolved oxygen is also minimized during manufacturing.

The claims of ’719 focus on a method of producing a storage stable ready-to-inject epinephrine composition. The method involves combining an aqueous carrier with epinephrine at a concentration of less than 0.07 mg/mL, ensuring the epinephrine is primarily the R-isomer, and maintaining low dissolved oxygen levels. The pH is adjusted, a specific metal ion chelator is added at a low concentration (1–50 mcg/mL), the composition is packaged under inert gas, and then sterilized. The resulting solution must be substantially antioxidant-free and maintain low impurity and S-isomer levels after storage.

In practice, the invention involves a multi-pronged approach to stabilize the epinephrine. The use of water for injection as the carrier, combined with a low concentration of a chelator like EDTA, helps to minimize metal-catalyzed degradation. Adjusting the pH to the specified range further enhances stability. The packaging under inert gas and subsequent sterilization, preferably autoclaving, ensures a sterile and stable product suitable for direct injection without prior dilution.

This approach differentiates itself from prior solutions by avoiding the use of antioxidants, which can cause allergic reactions. The low epinephrine concentration eliminates the need for dilution, reducing the risk of dosage errors. The combination of a specific pH range and a metal ion chelator, along with low dissolved oxygen, provides a synergistic effect, resulting in a formulation with improved stability and a longer shelf life compared to existing ready-to-inject epinephrine solutions.

How does this patent fit in bigger picture?

Technical landscape at the time

In the late 2010s when ’719 was filed, at a time when sterile pharmaceutical manufacturing commonly relied on multi-step processes to ensure product safety and stability. When dealing with oxygen-sensitive drugs, it was typical to use antioxidants to prevent degradation, even though such antioxidants could have their own drawbacks. When formulating low-concentration solutions, maintaining stability over extended storage periods was non-trivial.

Novelty and Inventive Step

The examiner allowed the claims because the prior art, specifically Sanghvi, does not teach or suggest the claimed method of producing an epinephrine composition. While Sanghvi discloses ready-to-inject epinephrine formulations with a metal ion chelator, tonicity agent, and preservative within a similar pH range, it teaches the use of antioxidants like metabisulfites. The examiner stated that Sanghvi fails to teach or suggest the specific range of metal ion chelator concentrations recited in the claims, particularly without the presence of an antioxidant to reduce epinephrine degradation.

Claims

This patent contains 19 claims, with claim 1 being the only independent claim. Independent claim 1 is directed to a method of producing a storage stable ready-to-inject epinephrine composition. The dependent claims generally elaborate on specific aspects of the method, such as sterilization techniques, concentration ranges, and composition characteristics.

Key Claim Terms New

Definitions of key terms used in the patent claims.

Term (Source)Support for SpecificationInterpretation
Aqueous pharmaceutically acceptable carrier
(Claim 1)		“In one aspect of the inventive subject matter, the inventors contemplate an antioxidant-free and storage stable ready-to-administer composition containing an oxygen-sensitive drug, for example, an epinephrine composition that includes an aqueous pharmaceutically acceptable carrier containing epinephrine.”A water-based medium suitable for pharmaceutical use, in which epinephrine is dissolved.
Metal ion chelator
(Claim 1)		“For example, suitable chelators include various bicarboxylic acids, tricarboxylic acids, and aminopolycarboxylic acids such as ethylenediaminetetraacetic acid (EDTA), ethylene glycol-bis(3-aminoethyl ether)-N,N,N′,N′-tetraacetic acid (EGTA), and penta(carboxymethyl)diethylenetriamine (DTPA), and salts and hydrates thereof. While not limiting to the inventive subject matter, it is contemplated that the metal ion chelators will slow down both the baseline and metal ion-stimulated autoxidation of epinephrine.”A compound that binds to metal ions, selected from EDTA, EGTA, and diethylenetriaminepentaacetic acid, to reduce metal-catalyzed degradation of epinephrine.
Ready-to-inject epinephrine composition
(Claim 1)		“Advantageously, the compositions presented herein have excellent storage stability even over extended periods, and have suitably low concentrations of epinephrine that allows administration of the composition directly to a patient at a very low dosage rate (e.g., 0.05-2.0 mcg/kg/min) without prior dilution.”A formulation of epinephrine that is at a low enough concentration that it can be administered directly to a patient without dilution.
Storage stable
(Claim 1)		“Advantageously, the compositions presented herein have excellent storage stability even over extended periods, and have suitably low concentrations of epinephrine that allows administration of the composition directly to a patient at a very low dosage rate (e.g., 0.05-2.0 mcg/kg/min) without prior dilution.”The epinephrine composition maintains its chemical integrity and potency over time, as measured by total impurities and S-isomer content.
Substantially antioxidant-free
(Claim 1)		“It should further be appreciated that contemplated compositions are substantially free of antioxidants (i.e., do not include antioxidants in an amount effective to reduce degradation of total epinephrine by at least about 1% when stored over a period of at least three months at 25° C.+/−2° C.). Therefore, and viewed from a different perspective, antioxidant-free and storage stable ready-to-administer epinephrine composition will include antioxidants in an amount of equal or less than about 0.01 wt %, or equal or less than about 0.005 wt %, or equal or less than about 0.001 wt %, or equal or less than about 0.0005 wt %, or equal or less than about 0.0001 wt %.”The epinephrine composition contains a minimal amount of antioxidants, such that they do not effectively reduce epinephrine degradation.

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US11071719

NOVAQUEST CO-INVESTMENT FUND X LP
Application Number
US16788831
Filing Date
Feb 12, 2020
Status
Granted
Expiry Date
Mar 21, 2039
External Links
Slate, USPTO, Google Patents