Alnylam Announces Grant of Tuschl II Patent in Japan

Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, announced today that the Japanese Patent Office has sent notification of an intent to grant a patent (JP Application Number 2002/546670) for the Tuschl II patent series, entitled "RNA Interference Mediating Small RNA Molecules.” The newly granted patent includes 39 claims broadly covering compositions, methods, uses, and systems for small interfering RNAs (siRNAs), the molecules that mediate RNAi. The grant of claims in the Japanese Tuschl II patent extends the issuance of the Tuschl II patent in the U.S. (U.S. Patent Nos. 7,056,704 and 7,078,196) and its grant in the European Union (EP 1407044), amongst other jurisdictions. As such, the Tuschl II patent series now provides Alnylam exclusivity for the claimed subject matter in the world’s top three pharmaceutical markets. The Tuschl II patent family is exclusively licensed to Alnylam for RNAi therapeutics on a worldwide basis through an agreement with Max Planck Innovation GmbH, the licensing agent for the Max Planck Society. "This first grant of the Tuschl II patent in Japan, the world’s third largest pharmaceutical market, further extends Alnylam’s leadership on intellectual property for RNAi therapeutics. This new achievement continues to broaden the scope of our ‘first-mover’ consolidation of early RNAi fundamental patents and patent applications, including those related to the Crooke, Kreutzer-Limmer, Glover, Tuschl I, and Tuschl II patent series,” said Barry Greene, President and Chief Operating Officer of Alnylam. "We continue to expect that many additional patents owned or licensed exclusively to Alnylam will be awarded, broadening the geographic and claim scope of our patent portfolio for all siRNAs.” "We are quite pleased that the Tuschl II patent series continues to be regarded by patent offices across the world as a seminal invention for RNAi,” commented Dr. Joern Erselius, Managing Director, Max Planck-Innovation GmbH. "Indeed, this successful examination of the Tuschl II patent highlights the importance of the work performed by Professor Tuschl and other co-inventors at the Max Planck Institute.” The claims for the newly granted Tuschl II patent cover compositions, methods, uses, and systems of double-stranded RNAs having key structural elements that are widely recognized as important for the therapeutic activity of siRNAs, including, in general terms: a double-stranded region formed from two RNA strands with a length of 19-23 nucleotides; at least one 3'-overhang at the ends of the double-stranded molecule; compositions with chemical modifications on the 3'-end of the siRNA to protect against degradation and/or the use of one or more nucleotide modification, such as phosphorothioate, 2'-O-Me, or 2'-F modifications, without any limitation to the number of such modifications; methods and uses of such siRNA molecules to achieve RNAi interference of mammalian or pathogen-derived genes both in vitro and in vivo; and, systems for in vitro target validation comprising animal cells, an siRNA, and pharmacologic agents. "These newly granted claims for Tuschl II in Japan provide Alnylam and its partners with unmatched exclusivity for the advancement of RNAi therapeutics,” said Donna Ward, Ph.D., Vice President of Intellectual Property of Alnylam. "Of course, we are also vigilantly pursuing prosecution of additional divisional applications based on the Tuschl lab inventions. These are generally described in the research published by the Tuschl lab and include broad investigations on the structure of siRNAs including length and terminal design features such as overhangs as well as blunt ends.” The claims of the new Japanese Tuschl II patent are provided on the company’s website, together with claims from other Alnylam owned or licensed patents. About Alnylam Intellectual Property (IP) Alnylam’s IP estate includes issued, allowed, or granted fundamental patents in many of the world’s major pharmaceutical markets that claim the broad structural and functional properties of RNAi therapeutic products. As it applies to the U.S. and EU, these include: the Crooke Patents (U.S. Patent Nos. 5,898,031 and 6,107,094 and EP 0928290) issued in over 12 countries and licensed exclusively from Isis Pharmaceuticals, Inc. to Alnylam for RNAi therapeutics, which cover compositions, methods, and uses of modified oligonucleotides to inactivate a target mRNA mediated by a double-stranded RNase, such as "RISC,” which is the cellular enzyme complex that mediates RNAi; the Kreutzer-Limmer I ’623 patent (EP 1144623) granted in August 2002, maintained in amended form in June 2006 and owned by Alnylam, which covers methods, medicaments, and uses of siRNAs having, among other structural features, a length of 15 to 21 base pairs; the Kreutzer-Limmer I ’945 patent (EP 1214945) granted in June 2005 and owned by Alnylam, which covers compositions, methods, and uses of siRNAs with a length between 15 and 49 nucleotides; the Kreutzer-Limmer I ’167 patent (DE 10080167) granted in October 2007 and owned by Alnylam, which covers pharmaceutical compositions and uses of siRNAs with a length between 15 and 49 nucleotides that target certain broad categories of mammalian genes; the Kreutzer-Limmer I ’235 patent (DE 10066235), granted in January 2008 and owned by Alnylam, which covers methods, uses, and medicaments of siRNAs, with a length between 15 and 49 nucleotides, expressed through a vector; the Kreutzer-Limmer II ’061 patent (EP 1352061), granted in May 2006 and owned by Alnylam, which covers therapeutic compositions, methods, and uses of siRNA and derivatives directed toward over 125 disease targets; the Glover ’375 patent (EP 1230375), granted in July 2005 and exclusively licensed to Alnylam from Cancer Research Technology Limited, which broadly covers compositions, methods, and uses of double-stranded RNAs to mediate the inhibition of target genes in mammalian cells; the Tuschl II ’704 patent (U.S. Patent No. 7,056,704) issued in June 2006 and exclusively licensed to Alnylam from the Max Planck Society, which broadly covers methods of making siRNAs to silence any and all disease targets; the Tuschl II ’196 patent (U.S. Patent No. 7,078,196) issued in July 2006 and exclusively licensed to Alnylam from the Max Planck Society, which broadly covers methods of making siRNAs with or without chemical modifications; the Tuschl II ’044 patent (EP 1407044), granted in January 2008 and exclusively licensed to Alnylam from the Max Planck Society, which broadly covers compositions, methods, and uses of siRNAs; and, the Tuschl II patent (JP Application Number 2002/546670) granted in February 2008 and exclusively licensed to Alnylam from the Max Planck Society, which broadly covers compositions, methods, uses, and systems of siRNAs; and, many divisional and continuing patent applications pending of the aforementioned issued or granted patents and additional patent applications pending, including patents and patent applications covering inventions by Fire and Mello (U.S. Patent No. 6,506,559), Tuschl, Hannon, and Kay. In addition to fundamental patents, Alnylam is the exclusive licensee in the field of RNAi therapeutics for more than 150 issued chemistry patents owned or controlled by Isis Pharmaceuticals, Inc. broadly covering chemical modifications, including motifs and patterns of modifications of oligonucleotides, including RNAi therapeutics. These patents include: phosphorothioate and 2’-O-methyl modifications of oligonucleotides (Buhr, U.S. Patent No. 6,476,205); 2’-Ribose modifications of oligonucleotides (Cook, U.S. Patent Nos. 5,670,633; 6,005,087; 6,531,584; and 7,138,517); chemical conjugates of oligonucleotides (Manoharan, U.S. Patent No. 6,153,737); and, "overhang,” blunt-end,” and nucleotide pairing design motifs (Woppmann et al., UK 2417727). In addition to fundamental and chemistry patents, Alnylam is also the exclusive licensee in the field of RNAi therapeutics for certain delivery patents, including those owned and controlled by Tekmira Pharmaceuticals, Inc. covering delivery of oligonucleotides, including RNAi therapeutics, with liposomal formulations. These patents include: formulations of oligonucleotides, including siRNAs, in cationic liposomes (Wheeler, U.S. Patent Nos. 5,976,567 and 6,815,432; and Semple, U.S. Patent No. 6,858,225). About RNA Interference (RNAi) RNAi (RNA interference) is a revolution in biology, representing a breakthrough in understanding how genes are turned on and off in cells, and a completely new approach to drug discovery and development. Its discovery has been heralded as "a major scientific breakthrough that happens once every decade or so,” and represents one of the most promising and rapidly advancing frontiers in biology and drug discovery today which was awarded the 2006 Nobel Prize for Physiology or Medicine. RNAi is a natural process of gene silencing that occurs in organisms ranging from plants to mammals. By harnessing the natural biological process of RNAi occurring in our cells, the creation of a major new class of medicines, known as RNAi therapeutics, is on the horizon. RNAi therapeutics target the cause of diseases by potently silencing specific messenger RNAs (mRNAs), thereby preventing disease-causing proteins from being made. RNAi therapeutics have the potential to treat disease and help patients in a fundamentally new way. About Alnylam Pharmaceuticals Alnylam is a biopharmaceutical company developing novel therapeutics based on RNA interference, or RNAi. The company is applying its therapeutic expertise in RNAi to address significant medical needs, many of which cannot effectively be addressed with small molecules or antibodies, the current major classes of drugs. Alnylam is leading the translation of RNAi as a new class of innovative medicines with peer-reviewed research efforts published in the world’s top scientific journals including Nature, Nature Medicine, and Cell. The company is leveraging these capabilities to build a broad pipeline of RNAi therapeutics; its most advanced program is in Phase II human clinical trials for the treatment of respiratory syncytial virus (RSV) infection. In addition, the company is developing RNAi therapeutics for the treatment of a wide range of disease areas, including hypercholesterolemia, liver cancers, and Huntington’s disease. The company’s leadership position in fundamental patents, technology, and know-how relating to RNAi has enabled it to form major alliances with leading companies including Medtronic, Novartis, Biogen Idec, and Roche. To reflect its outlook for key scientific, clinical, and business initiatives, Alnylam has established "RNAi 2010” which includes the company’s plan to significantly expand the scope of delivery solutions for RNAi therapeutics, have four or more programs in clinical development, and to form four or more new major business collaborations, all by the end of 2010. Alnylam is a joint owner of Regulus Therapeutics LLC, a joint venture focused on the discovery, development, and commercialization of microRNA therapeutics. Founded in 2002, Alnylam maintains headquarters in Cambridge, Massachusetts. For more information, visit www.alnylam.com. About Max Planck Innovation Max Planck Innovation advises and supports scientists of the Max Planck Society in evaluating inventions and filing patent applications. Max Planck Innovation markets patents and technologies to industry and coaches founders of new companies based on research results from Max Planck Institutes. Every year, Max Planck Innovation evaluates about 130 inventions, of which about 70 lead to the filing of a patent application. In the last five years alone, Max Planck Innovation advised 28 spin-offs, completed more than 450 license deals and generated proceeds of more than 100 million Euros for inventors, institutes, and the Max Planck Society. Max Planck Innovation operated under the name of Garching Innovation until October 2006. Alnylam Forward-Looking Statements Various statements in this release concerning Alnylam’s future expectations, plans and prospects, including its views with respect to the timing of the future issuance of patents and the expected validity, enforceability, importance and scope of its intellectual property rights, including the Tuschl II patents, constitute forward-looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including risks related to: Alnylam’s approach to discover and develop novel drugs, which is unproven and may never lead to marketable products; obtaining, maintaining and protecting intellectual property; Alnylam’s ability to enforce its patents against infringers and to defend its patent portfolio against challenges from third parties; Alnylam’s ability to obtain additional funding to support its business activities; Alnylam’s dependence on third parties for development, manufacture, marketing, sales and distribution of products; obtaining regulatory approval for products; competition from others using technology similar to Alnylam’s and others developing products for similar uses; Alnylam’s dependence on collaborators; and Alnylam’s short operating history; as well as those risks more fully discussed in the "Risk Factors” section of its most recent quarterly report on Form 10-Q on file with the Securities and Exchange Commission. In addition, any forward-looking statements represent Alnylam’s views only as of today and should not be relied upon as representing its views as of any subsequent date. Alnylam does not assume any obligation to update any forward-looking statements.