IP Verse

Compositions Comprising Ephedrine Or An Ephedrine Salt And Methods Of Making And Using Same

Patent No. US11426369 (titled "Compositions Comprising Ephedrine Or An Ephedrine Salt And Methods Of Making And Using Same") was filed by Isopro Holdings Llc on Dec 20, 2021.

What is this patent about?

’369 is related to the field of pharmaceutical formulations, specifically addressing the need for a stable and readily available form of ephedrine sulfate for clinical use. Currently approved ephedrine sulfate formulations require dilution before administration, which introduces potential for errors and contamination. The invention aims to eliminate this dilution step, providing a safer and more convenient product.

The underlying idea behind ’369 is to create a pre-diluted, sterile, and shelf-stable ephedrine sulfate solution that can be administered directly to patients without any prior preparation. This is achieved by carefully controlling the composition, including the concentration of ephedrine sulfate and the addition of an isotonic agent like sodium chloride, while excluding preservatives and chelating agents that could cause adverse reactions.

The claims of ’369 focus on a method of manufacturing a ready-to-use ephedrine sulfate composition. The method involves combining ephedrine sulfate, sodium chloride or dextrose, and water to form a solution with a specific concentration of ephedrine sulfate (5 mg/mL) and either sodium chloride (9 mg/mL) or dextrose (5%). The solution is then filtered, placed into sanitized containers, and sealed, resulting in a shelf-stable product that maintains its pH within a narrow range during long-term storage.

In practice, the invention involves a precise manufacturing process. The ephedrine sulfate, sodium chloride or dextrose, and water are mixed to achieve the desired concentrations. The pH is optionally adjusted to be between 4.5 and 7.0. The solution is then sterilized by filtration through a membrane filter. Finally, the sterile solution is aseptically filled into sterilized vials, which are then sealed to maintain sterility and stability. The absence of preservatives and chelating agents is crucial for minimizing potential patient sensitivities.

The key differentiation from prior approaches lies in the creation of a truly ready-to-use product that avoids the need for on-site dilution. Existing formulations require dilution, which increases the risk of contamination and dosage errors. By providing a stable, pre-mixed solution , the invention reduces these risks and simplifies the administration process, particularly in emergency situations where time is critical and complete patient information may not be immediately available.

How does this patent fit in bigger picture?

Technical landscape at the time

In the late 2010s when ’369 was filed, sterile pharmaceutical products were commonly manufactured using aseptic techniques. At a time when ready-to-use injectable formulations were desirable to reduce medication errors and improve efficiency, achieving long-term stability without preservatives or chelating agents was non-trivial. When formulating such products, manufacturers typically relied on established guidelines for sterilization, pH control, and isotonicity to ensure safety and efficacy.

Novelty and Inventive Step

The examiner allowed the claims because the applicant's amendment, which canceled claims 20-44, overcame all previous rejections. The examiner withdrew rejections based on 35 U.S.C. 101 and obviousness-type double patenting after the applicant filed a terminal disclaimer. The examiner also noted that the applicant provided an amended specification. The examiner considered the invention, as defined by the remaining claims, to be novel and allowable over the prior art.

Claims

This patent contains 9 claims, with claim 1 being the only independent claim. Independent claim 1 focuses on a method for producing a shelf-stable, ready-to-use ephedrine sulfate composition. The dependent claims elaborate on the characteristics of the composition produced by the method of claim 1, such as bacterial endotoxin levels, ephedrine levels, impurity levels, and particle size.

Key Claim Terms New

Definitions of key terms used in the patent claims.

Term (Source)Support for SpecificationInterpretation
9 mg/mL Sodium chloride or 5% dextrose
(Claim 1)		“In some embodiments, the isotonic agent is sodium chloride. In other embodiments, the isotonic agent is dextrose. In embodiments in which the isotonic agent is sodium chloride, the sodium chloride may be present in an isotonic amount, such as about 9 mg/mL. In embodiments in which the isotonic agent is dextrose, the sodium chloride may be present in an isotonic amount, such as about 5%.”The concentration of sodium chloride is 9 milligrams per milliliter, or the concentration of dextrose is 5%. These are isotonic agents.
Initial ephedrine sulfate level of 5 mg/mL
(Claim 1)		“In some embodiments, the ephedrine or ephedrine salt is present in an amount equivalent to about 3.8 mg/mL of ephedrine free base. For example and without limitation, embodiments in which the ephedrine or the ephedrine salt consists of ephedrine free base, the ephedrine free base may be present in an amount of about 3.8 mg/mL. In embodiments wherein the ephedrine or the ephedrine salt consists of ephedrine sulfate, the ephedrine sulfate may be present in an amount of about 5 mg/mL.”The starting concentration of ephedrine sulfate in the batch solution is 5 milligrams per milliliter.
Maintaining a pH level of the shelf-stable, ready-to-use ephedrine sulfate composition in the sealed containers that is within 0.5 pH units of the initial pH level
(Claim 1)		“In some embodiments, a composition of the present disclosure has a pH value of 4.5 to 7.0. In some embodiments, the composition has a pH value of 5.5 to 6.5. In some embodiments, the composition has a pH value of about 5.6 to 6.2. In some embodiments, the composition has a pH value of about 4.5, about 4.6, about 4.7, about 4.8, about 4.9, about 5.0, about 5.1, about 5.2, about 5.3, about 5.4, about 5.5, about 5.6, about 5.7, about 5.8, about 5.9, about 6.0, about 6.1, about 6.2, about 6.3, about 6.4, about 6.5, about 6.6, about 6.7, about 6.8, about 6.9, or about 7.0.”The pH of the composition remains relatively constant during storage, deviating no more than 0.5 pH units from its initial value.
No preservative
(Claim 1)		“In some embodiments, a composition of the present disclosure does not include a preservative. Non-limiting examples of preservatives include (e.g., benzyl alcohol, chlorobutanol, phenyl ethyl alcohol), parabens (e.g., methylparaben, ethylparaben, propylparaben, butylparaben), phenols (e.g., phenol, chlorocresol, o-phenyl phenol), mercurial compounds (e.g., thiomersal, nitromersol, phenylmercuric nitrate, phenylmercuric acetate), and quaternary ammonium compounds (e.g., benzalkonium chloride, cetyl pyridinium chloride). In some embodiments, the composition does not include benzyl alcohol.”The composition does not contain any preservative agents.
Shelf-stable, ready-to-use ephedrine sulfate composition
(Claim 1)		“The present disclosure provides compositions (e.g., ready-to-use premixed pharmaceutical compositions) comprising ephedrine or an ephedrine salt that are ready for immediate use in a clinical setting. The present disclosure is based in part on the inventor's discovery that pharmaceutical compositions consistent with those disclosed herein and comprising an ephedrine salt (e.g., ephedrine sulfate) in a premixed (e.g., ready-to-use) formulation that does not require reconstitution or dilution prior to administration to a subject remains stable and active after prolonged storage.”A composition containing ephedrine sulfate that is stable on the shelf and ready for immediate use without requiring further dilution or reconstitution. Stability is defined by maintaining pH within 0.5 units of the initial pH during specified storage conditions.

Litigation Cases New

US Latest litigation cases involving this patent.

Case NumberFiling DateTitle
1:25-cv-00018Jan 6, 2025Nexus Pharmaceuticals, Llc V. Hikma Pharmaceuticals Usa Inc.
1:22-cv-05683Sep 23, 2022NEXUS PHARMACEUTICALS, INC. v. NEVAKAR, INC. et al

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US11426369

ISOPRO HOLDINGS LLC
Application Number
US17556904
Filing Date
Dec 20, 2021
Status
Granted
Expiry Date
May 16, 2040
External Links
Slate, USPTO, Google Patents