IP Verse

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

Patent No. US11090278 (titled "Compositions Comprising Ephedrine Or An Ephedrine Salt And Methods Of Making And Using Same") was filed by Isopro Holdings Llc on May 16, 2020.

What is this patent about?

’278 is related to the field of pharmaceutical formulations, specifically addressing the need for a stable, ready-to-use injectable form of ephedrine sulfate . Ephedrine sulfate is a medication used to treat hypotension, particularly in anesthesia settings. Current FDA-approved 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 for clinical use.

The underlying idea behind ’278 is to create a pre-diluted ephedrine sulfate solution that maintains its stability and sterility over an extended period without requiring preservatives or chelating agents. This is achieved by carefully controlling the formulation's components and employing a terminal sterilization process. The key insight is that a simple formulation of ephedrine sulfate, sodium chloride, and water, when properly sterilized and packaged, can achieve the desired stability and eliminate the need for potentially harmful excipients.

The claims of ’278 focus on methods of administering a shelf-stable, ready-to-use ephedrine sulfate composition to a subject in need. The composition consists essentially of 5 mg/mL ephedrine sulfate, 9 mg/mL sodium chloride, and water, with no preservatives. The method involves drawing the composition from a sterile premixed pharmaceutical product into a syringe and injecting it into the subject. The claims also cover the preparation process, which includes combining the ingredients, placing the solution into depyrogenated glass vials, sealing the vials, and terminally sterilizing them.

In practice, the invention provides a clinician with a vial containing a pre-mixed, sterile solution of ephedrine sulfate at the correct concentration for injection. The clinician simply draws the solution into a syringe and administers it to the patient, eliminating the need for any on-site compounding or dilution. The terminal sterilization process ensures that the product is free from microbial contamination, reducing the risk of infection. The use of depyrogenated glass vials further minimizes the presence of endotoxins.

This approach differs significantly from prior methods that rely on concentrated ephedrine solutions requiring dilution. By providing a ready-to-use formulation, ’278 reduces the risk of medication errors associated with manual dilution, such as incorrect dosage or contamination. Furthermore, the absence of preservatives and chelating agents minimizes the potential for allergic reactions or adverse interactions with other medications, making it a safer option, especially in emergency situations where patient history may be incomplete. The long shelf life also makes it more practical for storage and use in clinical settings.

How does this patent fit in bigger picture?

Technical landscape at the time

In the late 2010s when ’278 was filed, sterile pharmaceutical compounding was typically performed using aseptic techniques, whether in a compounding lab or on-site by medical professionals, at a time when ready-to-use formulations often included preservatives and chelating agents to ensure stability, when hardware or software constraints made it non-trivial to guarantee long-term stability of pre-diluted ephedrine solutions without such excipients.

Novelty and Inventive Step

The examiner allowed the claims because the applicant's amendments overcame prior rejections. Specifically, the examiner had previously rejected certain claims as obvious over a reference (Akovaz) in view of another reference (CORPHEDRA brochure) and Griffiths et al., but withdrew this rejection. The examiner also withdrew a rejection of other claims as obvious over Akovaz, CORPHEDRA brochure, Griffiths et al., and Puri et al. The examiner stated that the claimed invention is novel and allowable over the prior art.

Claims

This patent contains 14 claims, of which claims 1 and 8 are independent. The independent claims are directed to methods of administering a ready-to-use ephedrine sulfate composition to subjects with hypotension or at risk of developing it. The dependent claims generally elaborate on specific aspects of the methods, such as sealing the vials, sterilization temperatures, pH levels, and storage conditions.

Key Claim Terms New

Definitions of key terms used in the patent claims.

Term (Source)Support for SpecificationInterpretation
Depyrogenated glass vials
(Claim 1, Claim 8)		“After mixing, the solution was filtered through Opticap XL 4 capsule durapore membranes (lot #18131597, Merck Millipore, Burlington, Mass.) before filling 10 cc clear glass type I vials (Lot #18500797, Gerresheimer/Bormioli, Dusseldorf, Germany) that had been washed and depyrogenized.”Glass vials that have been treated to remove pyrogens (substances that can cause fever).
Overkill terminal sterilization process
(Claim 8)		“The capped vials were crimped and sterilized by the overkill approach at 122.1° C. for 15 minutes in steel cassettes in an A601A autoclave.”A sterilization process that exceeds the minimum requirements for sterilization, ensuring a high level of sterility assurance.
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 reconstitution or dilution. It consists essentially of ephedrine sulfate, sodium chloride, no preservative, and water.
Shelf-stable ready-to-use ephedrine sulfate pharmaceutical product
(Claim 8)		“The present disclosure provides a shelf-stable composition comprising ephedrine or an ephedrine salt (e.g., ephedrine sulfate) that does not include a preservative, such as benzyl alcohol. In some embodiments, the shelf-stable composition comprises ephedrine or an ephedrine salt (e.g., ephedrine sulfate), an isotonic agent (e.g., sodium chloride) and water, but does not include a preservative (e.g., benzyl alcohol). In some embodiments, the shelf-stable composition comprises ephedrine sulfate (e.g., (−)-ephedrine sulfate), sodium chloride and water, but does not include benzyl alcohol.”A pharmaceutical product containing ephedrine sulfate that is stable on the shelf and ready for immediate use without requiring reconstitution or dilution, comprising 5 mg/mL +/- 5% ephedrine sulfate and no preservative.
Terminally sterilizing the sealed glass vials
(Claim 1, Claim 8)		“The capped vials were crimped and sterilized by the overkill approach at 122.1° C. for 15 minutes in steel cassettes in an A601A autoclave. Visual inspection of the terminally sterilized vials revealed no extraneous matter, low product volume or cosmetic defects. The sterilized vials passed sterility testing consistent with USP method <71> and passed bacterial endotoxins testing by USP method <87>1.7 Eu/mg).”Subjecting the sealed glass vials containing the ephedrine sulfate solution to a sterilization process at the end of the manufacturing process to eliminate any microorganisms.

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-06030Oct 11, 2022NEXUS PHARMACEUTICALS, INC. v. NEVAKAR, INC. et al
1:22-cv-05683Sep 23, 2022NEXUS PHARMACEUTICALS, INC. v. NEVAKAR, INC. et al

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US11090278

ISOPRO HOLDINGS LLC
Application Number
US16876020
Filing Date
May 16, 2020
Status
Granted
Expiry Date
May 16, 2040
External Links
Slate, USPTO, Google Patents