Marina Biotech Strengthens IP Estate for SMARTICLES Nucleic Acid Delivery Technology

Marina Biotech, Inc. recently announced the grant and issuance of patents relating to the company’s proprietary nucleic-acid delivery technology, SMARTICLES. The US Patent and Trademark Office (USPTO) has issued United States Patent No. 8,580,297 broadly covering the composition of matter and uses of novel conjugated amphoteric-amphiphilic molecules for delivery of nucleic acid-based therapeutics to control gene expression.

In addition, the Japan Patent Office (JPO) has granted the claims in SMARTICLES JP Application 2009-531787 broadly covering the combination of an anionic amphiphile, a cationic amphiphile, and a neutral amphiphile with parameters that cover a wide range of liposomal compositions.

SMARTICLES is currently in clinical development delivering both a single-stranded and a double-stranded oligonucleotide through licensees ProNAi Therapeutics, Inc. and Mirna Therapeutics, Inc., respectively. Recently at the 55th Annual Meeting of the American Society for Hematology in New Orleans, ProNAi presented safety and efficacy data from its ongoing Phase II study. ProNAi presented data demonstrating that PNT2258, their first-in-class BCL2 targeted drug, exhibited single agent anti-tumor activity in patients with recurrent or refractory Non-Hodgkin’s Lymphoma.

Further, PNT2258 is safe at a dose of 120 mg/m2 IV administered for 2-3 hours on days 1-5 of a 21-day schedule. No tumor lysis syndrome or major organ toxicities were observed. No occurrences of elevated liver enzymes, hyperkalemia, hyperphosphatemia, hypocalcemia, renal failure/dysfunction, or infections were noted.

“We are pleased that our patent estate continues to expand in order to protect those proprietary technologies that form the foundation of a flexible platform for the delivery of therapeutic nucleic acid molecules,” said J. Michael French, President and Chief Executive Officer at Marina Biotech, Inc. “Success in the design and formulation of delivery technologies is key to the development and commercialization of nucleic acid-based therapeutics. The SMARTICLES platform allows us to pursue a number of amphoteric liposome structures with enhanced delivery properties. Our broad delivery technologies permit the development of formulations for both targeted delivery, including the use of certain peptide-based moieties, as well as delivery via multiple routes of administration, such as subcutaneous injection. These patent issuances continue to support our broad drug discovery engine for the development of both single and double-stranded nucleic acid-based therapeutics.”

The US ‘297 patent encompasses the SMARTICLES delivery platform, which provides a broad range of amphoteric liposomes having structural features for improved serum stability and cargo loading for active substances including siRNA, miRNA, and antisense molecules. The advanced amphoteric liposomes of the US ‘297 patent are composed of an amphoteric group conjugated to a diglycerol amphiphile via flexible linkers. These structural features allow control of head group volume, isoelectric properties, and chargeability for improved delivery of nucleic acid-based therapeutics.

The conjugated amphoteric-amphiphilic platform encompasses a tunable isoelectric point to provide delivery formulations with both enhanced cellular permeability as well as pH-dependent endosomal release of nucleic acid cargoes. The new technology of the US ‘297 patent allows tailoring of SMARTICLES delivery molecules to provide novel therapeutic methods involving stable, non-toxic and highly effective delivery of nucleic acid agents.

The granted claims of the JP ‘787 application cover the use of novel molecules in the formulation of the company’s proprietary SMARTICLES delivery technology. For example, one such molecule has a unique cholesterol-hemisuccinate-morpholino structure that contains both a chargeable anion and a chargeable cation, as used in the company’s Amphoter II systems. Thus, these new delivery molecules have the advantage of being amphoteric over different anion to cation ratios, and the claims of the JP ‘787 application extend protection across a wide range of SMARTICLES-based formulations.

“We are pleased that the Japan Patent Office has recognized the significance of our approach to the delivery of therapeutic nucleic acids in man,” continued Mr. French. “We have long appreciated the important position of Japan in the global drug and pharmaceutical markets. The grant of the patent in Japan is a significant milestone for us.”

Marina Biotech is an oligonucleotide therapeutics company with the broadest drug discovery platform in the sector providing the ability to develop proprietary single and double-stranded nucleic acid therapeutics including siRNAs, microRNA mimics, antagomirs, and antisense compounds, including messengerRNA therapeutics. The platform was built via a roll-up strategy to discover and develop any number of different types of nucleic acid therapeutics in order to modulate (up or down) a specific protein(s) which is either being produced too much or too little causing a particular disease. For more information, visit www.marinabio.com.