Formulations Of Bendamustine
Patent No. US11103483 (titled "Formulations Of Bendamustine") was filed by Lsi Financing Llc on Jul 12, 2019.
What is this patent about?
’483 is related to the field of pharmaceutical formulations, specifically addressing the problem of long-term stability of bendamustine in liquid form. Bendamustine, used to treat various cancers, degrades rapidly in aqueous solutions, making it unsuitable for ready-to-use formulations. Existing lyophilized formulations require inconvenient and time-consuming reconstitution before administration.
The underlying idea behind ’483 is to create a stable, ready-to-use liquid formulation of bendamustine by using a non-aqueous solvent system in combination with a stabilizing agent . The inventors discovered that specific combinations of polyethylene glycol (PEG), propylene glycol (PG), and antioxidants or chloride salts significantly reduce bendamustine degradation over extended storage periods.
The claims of ’483 focus on a ready-to-use liquid bendamustine composition containing bendamustine (or a salt thereof) at a concentration of 10–100 mg/mL, polyethylene glycol, and a stabilizing amount of an antioxidant. The key feature is the low impurity level (less than 5% total impurities by HPLC) after at least 15 months of storage at 5–25°C.
In practice, the invention involves dissolving bendamustine in a pharmaceutically acceptable fluid, such as a mixture of PEG and PG, along with an antioxidant like thioglycerol or lipoic acid. The specific ratios of PEG to PG, as well as the concentration of the antioxidant, are optimized to minimize degradation. The resulting solution can then be directly administered or further diluted, eliminating the need for reconstitution.
This approach differs from prior art by avoiding aqueous solutions, which are known to cause rapid bendamustine degradation. The use of PEG, particularly in high concentrations, slows down ester formation and reduces the formation of bendamustine degradants. The addition of antioxidants or chloride salts further enhances stability by inhibiting hydrolysis and other degradation pathways, resulting in a long-term stable, ready-to-use bendamustine formulation .
How does this patent fit in bigger picture?
Technical landscape at the time
In the early 2010s when '483 was filed, at a time when pharmaceutical formulations commonly relied on excipients to enhance drug stability and solubility, and when analytical techniques such as HPLC were routinely used to quantify drug degradation products.
Novelty and Inventive Step
The claims were rejected in a final office action. The rejections were based on obviousness and nonstatutory double patenting. Arguments were presented by the applicant, but the examiner maintained the rejections. The prosecution record does NOT describe the technical reasoning or specific claim changes that led to allowance.
Claims
This patent contains 17 claims, with claim 1 serving as the independent claim. The independent claim focuses on a ready-to-use liquid bendamustine composition with specific concentration ranges, polyethylene glycol, an antioxidant, and impurity levels. The dependent claims generally elaborate on specific components, concentrations, and methods of using the composition described in the independent claim.
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Date
Description
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US11103483
- Application Number
- US16509920
- Filing Date
- Jul 12, 2019
- Status
- Granted
- Expiry Date
- Jan 28, 2031
- External Links
- Slate, USPTO, Google Patents