Liposomes co-encapsulating a bisphosphonate and an amphipathic agent

US10085940B2 · kind B2 · utility

Assignees

• YISSUM RESEARCH DEVELOPMENT COMPANY OF THE HEBREW UNIVERSITY OF JERUSALEM LTD. · IL
• KING'S COLLEGE LONDON · GB
• Shaare Zedek Scientific Ltd. · IL

Inventors

• Alberto Gabizon · San Francisco, US
• Yechezkel Barenholz · Jerusalem, IL
• Hilary Shmeeda · Ramat HaSharon, IL
• John Maher · London, GB
• Ana Catarina Parente Pereira · London, GB

Key dates

• Filing date: Jul 12, 2012
• Grant date: Oct 2, 2018
• Expiry date: May 2, 2035

Classification

• Technology area (CPC A): Human Necessities
• CPC primary: A61K2039/55555
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

The present disclosure provides liposomes comprising a membrane and an intraliposomal aqueous water phase, the membrane comprising at least one liposome forming lipid and the intraliposomal aqueous water phase comprises a salt of a bisphosphonate together with an amphipathic weak base agent (PLAD). An example of a liposome is one comprising co encapsulated in the intraliposomal aqueous water phase N-containing bisphosphonate, such as alendronate, and an anthracycline such as doxorubicin which was shown to increase survival as compared to Doxil or to administrations of liposomal alendronate (PLA) and Doxil (separate liposomes). Such liposomes may carry a targeting moiety exposed at the liposome's outer surface, for example, conjugate of folic acid as a targeting moiety to folate receptor (FT-PLAD). Also provided by the present disclosure is a method of preparing the liposomes and methods of use of the liposomes, at times, in combination with additional active ingredients, such as γδ T-cells.