Alnylam Provides Update on Kreutzer-Limmer Patent Family

CAMBRIDGE, Mass.– Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, announced today that the European Patent Office (EPO) has ruled in favor of the opposing parties in oral proceedings before the European Opposition Board related to the ‘945 (EP 1214945) patent in its Kreutzer-Limmer patent estate. This ruling does not affect other granted claims of the Kreutzer-Limmer patent series, nor does it affect the ongoing examination of other applications in this patent family, which the company expects will result in new granted patents. In addition, the ruling of this Opposition Hearing is not considered final and can be appealed.

The ‘945 patent is only one of a number of patents in the Kreutzer-Limmer estate. Other distinct patents in the family include EP 1550719, or ‘719, which covers siRNAs comprising 15-21 nucleotides in length stabilized by chemical linkages. In addition, patents from the Kreutzer-Limmer patent family have been granted in other countries, including Germany (DE 10080167 and DE 10066235) with claims covering siRNAs with lengths of 15-49 nucleotides. Many additional patents from the Kreutzer-Limmer patent family are pending in the U.S., Japan, and other countries.

“Notwithstanding the current outcome for the ‘945 patent in the European Opposition Proceedings, Alnylam maintains an unparalleled intellectual property position that we believe is needed for the development and commercialization of all RNAi therapeutics. In addition, we strongly believe in the inventive matter described in the ‘945 patent and we intend to take the next step and appeal the decision made today through the EPO’s appeal process,” said Barry Greene, President and Chief Operating Officer of Alnylam. “The Kreutzer-Limmer patent family is broad and is comprised of numerous pending applications for which we expect new patent grants and issuances to emerge. Of course, no single patent or patent family defines the full breadth of Alnylam’s intellectual property position. We have a clear track record of leveraging our intellectual property 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 believe that the EPO will recognize the importance of these early discoveries in the RNAi field and that consideration of parallel filings will continue to yield significant patents, such as the new ‘719 patent announced recently,” 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 intellectual property (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 317 have issued or been granted in the U.S., Europe, or Japan, the world’s largest pharmaceutical markets; together, these define the company’s IP estate for RNAi therapeutics. In addition to the Kreutzer-Limmer patent family, Alnylam’s fundamental IP estate includes exclusive licenses to the Crooke, Glover, and Tuschl II patent families, and the Li & Kirby, Pachuk I, and Giordano patent families obtained from its acquisition of the patent assets from Nucleonics, Inc. It also includes a co-exclusive license to the Tuschl I patent family and a non-exclusive license to the Fire & Mello patent.

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:

— 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 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 ‘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 ‘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 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;

— 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;

— 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 & Mello (U.S. Patent No. 6,506,559), Glover, Li &

Kirby, Pachuk, Tuschl, Hannon, Giordano, 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 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. 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).

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