MDRNA, Inc., a leading RNAi-based drug discovery and development company, announced that the US Patent and Trademark Office (USPTO) has issued a Notice of Allowance for patent application US 12/701,397 covering methods for the delivery of siRNAs as well as a broad array of compounds with pharmacological activity. The patent identifies and protects peptides that were discovered using MDRNA's proprietary Trp Cage Phage Display Library and describes targeting peptides that demonstrate high binding affinity to, and internalization by, hepatocellular carcinoma cells.

"Specificity to individual cell types and internalization are key attributes required for peptide-directed delivery," said Barry Polisky, Ph.D., chief scientific officer of MDRNA. "The Trp Cage Phage Display Library is proving to be a robust means to screen and identify peptides that impart these targeting characteristics. The addition of these novel peptides to our proprietary DiLA2 delivery platform technology permits the potential development of highly tissue- and cell-specific RNAi-based therapies for the treatment of cancers in which the need to differentiate between normal and diseased cells is important."

MDRNA's proprietary Trp Cage Phage Display Library (J Biol Chem. 2007 282(13):9813) is the subject of an issued patent, US patent 7,329,725. The Trp Cage motif is highly structured allowing for the identification of peptides with high binding affinity for specific cell or tissue types, and avoids the limitations and weak binding often associated with linear peptide libraries. This technology is directly applicable to the Company's DiLA2 delivery platform as peptides are readily conjugated to the amino acid scaffold of a DiLA2. Peptides capable of directed delivery are expected to further improve the delivery efficiency of UsiRNAs, which have demonstrated significant knockdown of target genes in mouse models of liver and bladder cancer, and in non-human primates.

"This is the second Notice of Allowance that we have received in the past four months from the USPTO for a patent application that covers the use of our proprietary targeting peptide technology," said J. Michael French, president and CEO of MDRNA. "We are pleased that the USPTO recognizes the novelty and significance of our proprietary peptide targeting technology. The identification of additional peptides with high affinity to specific cell types, including certain cancers, further strengthens our broad patent estate."

On December 17, 2009, MDRNA received a Notice of Allowance from the USPTO for patent application US 11/627,863, which covers the use of targeting peptides that have preferential binding affinity for lung tissue.

MDRNA has a broad intellectual property estate that encompasses four key RNAi technology platforms: siRNA constructs, chemistry, nucleic acid delivery, and gene targets. The MDRNA-owned siRNA constructs and chemistry include its proprietary UsiRNA construct, which is a duplex siRNA chemically modified with non-nucleotide acyclic monomers (UNAs), and is distinct from the standard siRNA construct used by others in the industry. UsiRNAs are fully recognized by the RNAi machinery and provide for potent RNAi activity while specific placement of UNAs in a duplex siRNA minimizes potential off-target effects by the guide strand and reduces undesired passenger strand activity. Furthermore, UsiRNAs escape the surveillance mechanisms associated with cytokine induction, and provide protection from nuclease degradation.

The MDRNA delivery platforms include DiLA2 and nanoparticle forming peptides. DiLA2 is an MDRNA proprietary delivery platform of novel synthetic di-alklylated amino acid compounds used to make liposomal delivery formulations. The DiLA2 platform enables MDRNA to tailor the charge, linker and acyl chains of amino acids in order to configure liposomes for delivery to target tissues of interest. In addition, the platform is designed to permit attachment of various peptides and other targeting molecules to improve a variety of delivery characteristics. The MDRNA peptide nanoparticle platform includes exclusively in-licensed and developed IP surrounding the use of peptides for nanoparticle formulations that increase cellular uptake and endosomal release of siRNAs. MDRNA is currently biopanning its patented phage display library to identify additional peptides for targeted delivery, cellular uptake and endosomal release of siRNA.

MDRNA owns or controls 16 issued or allowed patents, and has 36 pending patent applications, 126 pending foreign patent applications and 7 PCT applications.