BioNTech SE has recently (09.09.2022) filed a PCT patent application (WO2023036960, inventors: Hossam Hefesha, Heinrich Haas, Ferdia Bates, Christian Hotz and Katalin Karikó) published on 16.03.2023.
The invention describes a method of producing a composition comprising RNA lipoplex particles comprising phosphatidylserine. The RNA encodes peptides or polypeptides such as cytokines, hormones, adhesion molecules, immunoglobulins, immunologically active compounds, growth factors, protease inhibitors, enzymes, receptors, apoptosis regulators, transcription factors, tumor suppressor proteins, structural proteins, reprogramming factors, genomic engineering proteins or blood proteins. The main focus of the description is antitumoral therapy.
The formulation itself is an acidified aqueous colloidal suspension comprising liposomes, wherein the liposomes contain phosphatidylserine and acetic acid. The aqueous colloidal suspension of liposomes is combined with an aqueous solution comprising RNA; thereby producing the composition comprising RNA lipoplex particles. The formulation requires frozen storage conditions, hence the use of cyroprotectant is necessary. Mono- di- and oligosaccharides are proposed by the invention to protect such compositions, including various cyclodextrins including cyclodextrin polymers and partially etherified monomeric cyclodextrin derivatives. In the formulation examples, only sucrose was actually used as cryoprotectant.
Use of cyclodextrins as cryoprotectants and stabilizers in biopharmaceutical formulations is an emerging technology already discussed in earlier posts.
BioNTech SE is still developing the final formulation and we cannot wait if it turns out that pharmaceutically acceptable cyclodextrins, such as HPBCD or SBECD eventually outperform simpler carbohydrates in stabilizing potency in one way or the other in groundbreaking therapeutic products as RNA-based antitumoral formulations.
Image credits: Wikimedia Commons