Neuroblastoma treatment with taurolidine hydrolysis products
Inventors
Reidenberg, Bruce • DiLuccio, Robert
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-11541061-B2
Publication Date
2023-01-03
Expiration Date
Abstract
Neuroblastoma is a tumor primarily affecting children. The current standard of care is not curative except in the rare case of a surgically-resectable lesion, although very high survival rates have been documented for low-risk neuroblastoma and moderate-risk neuroblastoma. Taurolidine was developed as an anti-infective, but it has been found to have surprising oncolytic activity in cell cultures and now in a rodent cancer model. The efficacy in rodent model is superior to the efficacy in cell culture. This invention relates to the use of taurolidine hydrolysis products (tarultam and/or taurinamide and/or methylene glycol and/or selected combinations thereof) for the treatment of neuroblastoma in juvenile mammals.
Core Innovation
The patent describes taurolidine hydrolysis products, including taurultam and taurinamide, for treating neuroblastoma in juvenile mammals. It focuses on formulations where taurultam and taurinamide are used with defined weight ratios, including a taurultam:taurinamide weight ratio of 1:7, and optionally includes taurolidine hydrolysis product compositions involving methylene glycol in defined weight-ratio relationships.
The document links these hydrolysis products to anti-neoplastic effects using in vitro sensitivity of neuroblastoma cell lines and in vivo tumor-efficacy in CB57 SCID mouse xenograft models. It describes statistically significant tumor size decreases in tumor models, including IMR5 tumors and SK-N-AS tumors, supporting activity of the taurolidine hydrolysis product compositions for neuroblastoma treatment.
To address premature hydrolysis, the patent describes shielded systemic delivery approaches in which a composition is pegylated using polyethylene glycols to delay premature hydrolysis until tumor arrival. It further describes delivery approaches using nanoparticles with exterior coatings that prevent premature degradation, including absorbable polymer or lipid coatings, with optional PEGylation and optional targeting via anti-N-type calcium channel binding molecules.
Claims Coverage
The independent claim contains inventive features covering a defined taurultam/taurinamide weight ratio with specified dosage ranges, PEGylation using polyethylene glycols to delay premature hydrolysis, and administration from once daily through weekly for an effective period based on the patient's response.
PEGylated taurultam and taurinamide weight ratio for treating neuroblastoma
A method for treating neuroblastoma by administering a composition comprising taurultam and taurinamide in a weight ratio of 1 taurultam:7 taurinamide, with a dosage range of taurultam between 5 mg/kg and 40 mg/kg and a dosage range of taurinamide from 35 mg/kg to 280 mg/kg.
PEGylation to delay premature hydrolysis
The composition is pegylated using polyethylene glycols to delay premature hydrolysis of the composition.
Once daily through weekly administration based on response
The composition is administered from once daily through weekly, for an effective period of time based on the patient's response.
Combination with an oncolytic agent and/or radiotherapy
The method further provides administering the composition together with an oncolytic agent and/or radiotherapy.
Parenteral administration routes
The method delivers the composition to a patient using parenteral, intramuscular, or intravenous delivery.
Overall, the claim coverage centers on treating neuroblastoma using a PEGylated composition containing taurultam and taurinamide at a defined 1:7 weight ratio with specified dosage ranges, administered once daily through weekly for an effective period based on patient response, with dependent variations including combination with an oncolytic agent and/or radiotherapy and restricted administration routes.
Stated Advantages
Delays premature hydrolysis of the composition using PEGylation.
Documented Applications
Treating neuroblastoma in juvenile mammals using compositions containing taurolidine hydrolysis products (taurultam and taurinamide).
Using in vitro sensitivity of neuroblastoma cell lines and in vivo CB57 SCID mouse xenograft models (IMR5 tumors and SK-N-AS tumors) with tumor size decrease as documented efficacy support.
Interested in licensing this patent?