CAMBRIDGE, Mass.–Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, announced today that the European Patent Office (EPO) has upheld its “Kreutzer-Limmer II” ’061 (EP 1352061) patent in oral proceedings held before the European Opposition Board. The ’061 patent is the first to be granted in Europe from the Kreutzer-Limmer II patent family, and includes broad claims covering methods of silencing approximately 130 disease genes with small interfering RNAs, or “siRNAs,” the molecules that mediate RNAi, which in this case comprise certain stabilizing design features and lengths of up to 49 nucleotides.

The maintenance of all originally granted claims in the Kreutzer-Limmer II ’061 patent reinforces the strength of Alnylam’s overall intellectual property (IP) estate which is believed by the company to be needed for the development and commercialization of RNAi therapeutics. The ’061 patent was challenged by a single opponent, Sirna Therapeutics, Inc., a wholly-owned subsidiary of Merck & Co., Inc., whose request to revoke the patent was denied.

“We are gratified with the EPO’s decision to support the ’061 patent from our Kreutzer-Limmer II patent series. This patent has broad and significant claims related to methods for inhibiting the expression of a large number of important disease target genes,” said Barry Greene, President and Chief Operating Officer of Alnylam. “Today’s ruling affirms Alnylam’s overall IP estate as a required component for development and commercialization of all RNAi therapeutics. Alnylam has leveraged this IP estate to enable the field with freedom to operate for RNAi therapeutics as evidenced by more than 25 licensing agreements which have yielded over $660 million in realized cash funding, and we expect this to continue in the future.”

“We are very pleased that the EPO has recognized the importance and patentability of our early discoveries in the RNAi field,” said Roland Kreutzer, Ph.D., Head of Roche’s Center of Excellence for RNA Therapeutics in Kulmbach, Germany, and an inventor on the Kreutzer-Limmer patent series. “We are very excited about the progress being made in the field of RNAi research and are absolutely committed to advancing RNAi therapeutics to patients. Clearly, a strong IP estate is critical for the success of such an endeavor, and Alnylam and its partners, such as Roche, uniquely enjoy this benefit.”

Alnylam’s IP position is comprised of fundamental, chemistry, and target IP that the company believes is necessary for the development and commercialization of RNAi therapeutics. In aggregate, Alnylam owns or has in-licensed over 1,800 active patent cases, of which over 700 have issued or been granted worldwide, and over 300 have issued or been granted in the U.S., Europe, or Japan, the world’s largest pharmaceutical markets.

The claims of the ’061 patent cover methods of inhibiting the expression of target genes using double-stranded RNAs (dsRNAs):

* comprised of a length of up to 49 nucleotides;

* comprised of a single 3’ nucleotide “overhang” and a 5’ “blunt end” on the antisense strand, which provides intrinsic stabilization for the dsRNA; and,

* with or without additional chemical modifications.

The methods or uses of these siRNAs are directed toward approximately 130 disease targets, including all dsRNAs that are complementary to these genes; a list that include oncogenes, cytokines, angiogenesis pathway genes, apoptosis pathway genes, and cell adhesion genes, amongst others.

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. These include, but are not limited to:

the Crooke Patents (U.S. Patent Nos. 5,898,031, 6,107,094, 7,432,249, 7,432,250 and EP 0928290) issued in over 15 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 Glover ’375 patent (EP 1230375), granted in July 2005, licensed exclusively to Alnylam from Cancer Research Technologies, Ltd., and currently under appeal, which covers therapeutic uses of double-stranded RNA expressed from endogenous templates or expression vectors to mediate RNA interference in mammalian cells;

* the Kreutzer-Limmer I ’719 patent (EP 1550719), owned by Alnylam and where the company has received a notification of ‘intent to grant’, which covers siRNAs comprising 15-21 nucleotides in length stabilized by chemical linkages;

* 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 I ’945 patent (EP 1214945) granted in June 2005, currently under appeal, 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, currently under appeal, 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 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 approximately 130 disease targets;

* the Tuschl I patent (EP1309726) which received an intent to grant in April 2009 and exclusively licensed to Alnylam from the Max Planck Society, the Massachusetts Institute of Technology, and Whitehead Institute, which covers methods for using certain dsRNAs for RNAi;

* 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 target genes;

* 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;

the Tuschl II patent (JP 4 095 895) granted in May 2008 in Japan and exclusively licensed to Alnylam from the Max Planck Society, which broadly covers compositions, methods, uses, and systems of siRNAs;

* the Tuschl II patent (Application No. 01820900.9) in China which received an intent to grant in April 2009 and exclusively licensed to Alnylam from the Max Planck Society, which broadly covers compositions, methods, uses, and systems for siRNAs;

* the Kay & McCaffrey patent (AU patent application no. 2002326410) granted in February 2009 in Australia and exclusively licensed to Alnylam from Stanford University, which broadly covers methods and composition for RNAi therapeutics including siRNAs and shRNAs; 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 Crooke, Fire & Mello (U.S. Patent No. 6,506,559), Kreutzer & Limmer, Glover, Li & Kirby, Pachuk, Tuschl, Hannon, Giordano, and Kay & McCaffrey, amongst others.

In addition to fundamental patents, Alnylam is the exclusive licensee in the field of RNAi therapeutics for more than 175 issued chemistry patents owned or controlled by Isis Pharmaceuticals 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), which is owned by Alnylam.

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., broadly 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).

In addition, Alnylam is contributing on a royalty-free/non-profit basis its technology and more than 1500 issued or pending patents from its RNA interference patent estate to the patent pool initiated by GSK earlier in 2009. The patent pool was formed to aid in the discovery and development of new medicines for the treatment of 16 neglected tropical diseases (NTD), as defined by the U.S. Food and Drug Administration, in the world’s least developed countries.

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 and is partnered with Cubist and Kyowa Hakko. In addition, the company is developing RNAi therapeutics for the treatment of a wide range of disease areas, including liver cancers, hypercholesterolemia, Huntington’s disease, and TTR amyloidosis. 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, Roche, Takeda, Kyowa Hakko, and Cubist. To reflect its outlook for key scientific, clinical, and business initiatives, Alnylam established “RNAi 2010” in January 2008 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, 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, please visit https://www.alnylam.com.

Alnylam Forward-Looking Statement

Various statements in this release concerning Alnylam’s future expectations, plans and prospects, 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 the company’s ability to successfully research and develop products and to successfully prosecute and enforce its patents around the world, 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.