Alnylam Announces Allowance of U.S. Patent Broadly Covering RNAi Therapeutics; Patent Rights for Tuschl II are Held Exclusively by Alnylam for Development and Commercialization of RNAi Therapeutics

Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leadingRNAi therapeutics company, announced today that the United StatesPatent and Trademark Office (USPTO) has allowed claims in a patentapplication that broadly covers methods for preparing smallinterfering RNAs (siRNAs), the molecules that mediate RNAi. The USPTOissued a 'Notice of Allowance' for patent application 10/832,248 inthe 'Tuschl II' patent series. The patent series is exclusivelylicensed to Alnylam for RNAi therapeutics on a world-wide basisthrough an agreement with Garching Innovation GmbH, the licensingagent for the Max Planck Society. Based on the seminal research byThomas Tuschl, Ph.D., a founder of Alnylam, the newly allowed claimsbroadly cover methods of making siRNAs for any target, with or withoutchemical modifications. Following a 'Notice of Allowance', the finalissuance of a patent involves several administrative steps thattypically are completed within three months.

"In my view, this positive evaluation from the U.S. patent officevalidates the significance of our important findings published inNature and other scientific journals(1) in 2001," said Thomas Tuschl,Ph.D., Associate Professor, The Rockefeller University. "Our publishedstudies launched the broad use of RNAi as a tool for post-genomicresearch and pointed to a clear opportunity for development of RNAifor therapeutic gene silencing. It is very gratifying to see theimportance of our discovery of key structural features of siRNAsrecognized in this way."

"Our exclusive rights to the Tuschl II patent series are a majorcomponent of Alnylam's IP leadership," said John Maraganore, Ph.D.,President and Chief Executive Officer of Alnylam Pharmaceuticals."This U.S. patent represents an important strategic asset for Alnylam,and the allowance of claims by the USPTO solidifies our broad rightsrelating to the development and commercialization of RNAitherapeutics. This will further extend and strengthen our IP positionin RNAi, which we have leveraged over the last several years to buildsignificant value through 18 separate collaboration or licenseagreements with major pharmaceutical companies, biotechnologycompanies, and research product suppliers."

The allowed Tuschl II patent includes 79 claims that broadly coverthe preparation of a double-stranded RNA having key structuralelements that we believe are important for the therapeutic activity ofsiRNAs, including:

-- The presence of 3'-overhangs at one or both ends of the double-stranded molecule; and

-- A length of 19-25 nucleotides.

The claims also cover an siRNA with these structural elements thatalso incorporates any of various chemical modifications, including theuse of phosphorothioates, 2'-O-methyl, and/or 2'-fluoro modifications.These internal and backbone modifications are believed to be importantfor achievement of 'drug-like' properties for RNAi therapeutics. Theclaims cover siRNAs with the aforementioned structural properties thatare directed toward any and all target genes. The Tuschl II patentseries is distinct in inventorship and ownership from the so-called'Tuschl I' patent series for which Alnylam also holds a license.

In addition to the Tuschl II patents covering RNAi therapeutics,Alnylam's IP estate includes certain 'fundamental' patents and patentapplications that claim the broad structural and functional propertiesof synthetic RNAi products. These include the Kreutzer-Limmer I and IIpatents, acquired through the Ribopharma merger: EP Patent No.1144623, covering methods, medicaments and uses of siRNAs with up to25 nucleotides complementary to a target gene; EP Patent No. 1214945,covering compositions, methods, and uses of siRNAs with a lengthbetween 15 and 49 nucleotides; and EP Patent No. 1352061 coveringtherapeutic compositions, methods, and uses of siRNA and derivativesdirected toward over 125 disease targets. Additional fundamentalpatents and patent applications licensed to Alnylam on an exclusive ornon-exclusive basis include those of Crooke (U.S. Patent Nos.5,898,031 and 6,107,094), Fire and Mello (U.S. Patent No. 6,506,559),Glover et al. (EP Patent No. 1230375), and Tuschl et al. (Tuschl I,patent pending), amongst others.

Alnylam has leveraged its intellectual property assets throughresearch, development, and commercialization alliances with Merck andCo., Inc., Medtronic, Inc., and Novartis AG, through target-by-targetInterfeRx(TM) licenses or options granted to Nastech, Inc., GeneCareResearch Institute Co., Ltd., and Benitec Ltd., and through licenseagreements in the research reagent and services markets with multiplecompanies including Invitrogen Corporation, Sigma-Aldrich Corporation,Ambion, Inc., QIAGEN N.V., Dharmacon, Inc., and others.

About RNA Interference (RNAi)

RNA interference, or RNAi, is a naturally occurring mechanismwithin cells for selectively silencing and regulating specific genes.Since many diseases are caused by the inappropriate activity ofspecific genes, the ability to silence genes selectively through RNAicould provide a new way to treat a wide range of human diseases. RNAiis induced by small, double-stranded RNA molecules. One method toactivate RNAi is with chemically synthesized small interfering RNAs,or siRNAs, which are double-stranded RNAs that are targeted to aspecific disease-associated gene. The siRNA molecules are used by thenatural RNAi machinery in cells to cause highly targeted genesilencing.

About Alnylam

Alnylam is a biopharmaceutical company developing noveltherapeutics based on RNA interference, or RNAi. The company isapplying its therapeutic expertise in RNAi to address significantmedical needs, many of which cannot effectively be addressed withsmall molecules or antibodies, the current major classes of drugs.Alnylam is building a pipeline of RNAi therapeutics; its lead programis in Phase I human clinical trials for the treatment of respiratorysyncytial virus (RSV) infection, which is the leading cause ofhospitalization in infants in the U.S. The company's leadershipposition in fundamental patents, technology, and know-how relating toRNAi has enabled it to form major alliances with leading companiesincluding Merck, Medtronic, and Novartis. The company, founded in2002, maintains global headquarters in Cambridge, Massachusetts, andhas an additional operating unit in Kulmbach, Germany. For moreinformation, please visit www.alnylam.com.

Alnylam Forward-Looking Statements

Various statements in this release concerning our futureexpectations, plans and prospects, including our views with respect totiming of the issuance of patents and the importance and scope of ourintellectual property rights, constitute forward-looking statementsfor the purposes of the safe harbor provisions under The PrivateSecurities Litigation Reform Act of 1995. Actual results may differmaterially from those indicated by these forward-looking statements asa result of various important factors, including risks related to: ourapproach to discover and develop novel drugs, which is unproven andmay never lead to marketable products; obtaining, maintaining andprotecting intellectual property utilized by our products; our abilityto enforce our patents against infringers and to defend our patentportfolio against challenges from third parties; our ability to obtainadditional funding to support our business activities; our dependenceon third parties for development, manufacture, marketing, sales anddistribution of our products; the successful development of products,all of which are in early stages of development; obtaining regulatoryapproval for products; competition from others using technologysimilar to ours and others developing products for similar uses;; ourdependence on collaborators; and our short operating history; as wellas those risks more fully discussed in the "Certain Factors That MayAffect Future Results" section of our most recent quarterly report onForm 10-Q on file with the Securities and Exchange Commission. Inaddition, any forward-looking statements represent our views only asof today and should not be relied upon as representing our views as ofany subsequent date. We do not assume any obligation to update anyforward-looking statements.
(1) Elbashir, SM, Harboth J, Lendeckel W, Yalcin A, Weber K, Tuschl T
Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured
mammalian cells.
Nature (2001) 411, 494-498.

Elbashir SM, Martinez J, Patkaniowska A, Lendeckel W, Tuschl T
Functional anatomy of siRNAs for mediating efficient RNAi in
Drosophila melanogaster embryo lysate.
EMBO J. (2001) 20:6877-88.

Elbashir SM, Lendeckel W, Tuschl T
RNA interference is mediated by 21- and 22-nucleotide RNAs.
Genes Dev. (2001) 15:188-200.