Alnylam Pharmaceuticals update on Kreutzer-Limmer patent estate

Dec 10 2008

Alnylam Pharmaceuticals, Inc. has announced that the European Patent Office (EPO) has ruled in favor of the Appellants in oral proceedings before the Board of Appeals related to the '623 (EP 1144623) 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, which the company expects will result in new granted patents. Alnylam also announced today that the EPO intends to grant a new patent from the Kreutzer-Limmer patent family, EP 1550719, or '719, which covers siRNAs comprising 15-21 nucleotides in length stabilized by chemical linkages.

The '623 patent is only one of a number of patents in the Kreutzer-Limmer patent family. Other distinct and independently granted patents in the family include EP 1214945, or '945, which covers compositions, methods, and uses of siRNAs with a length between 15 and 49 nucleotides, and the '719 patent announced today. 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 '623 patent in the European Appeal Proceedings, Alnylam maintains an unparalleled IP position that we believe is needed for the development and commercialization of all RNAi therapeutics. The Kreutzer-Limmer patent family is broad and has many granted patents including the '945 patent, the '719 patent where we're extremely pleased to have recently received a notification of 'intent to grant', and numerous pending applications," said Barry Greene, President and Chief Operating Officer of Alnylam. "Moreover, the Kreutzer-Limmer patent family is also comprised of numerous pending applications for which we expect new patent grants and issuances to emerge that are only strengthened in our prosecution efforts by the arguments our opponents have levied against the first, more narrowly granted patent from this family. Of course, Alnylam has leveraged its IP estate to enable the field with freedom to operate for RNAi therapeutics as evidenced by over 25 licensing agreements yielding about $625 million in realized cash funding, and we expect this to continue in the future."

"We maintain that the EPO will recognize the importance of our early discoveries in the RNAi field and that consideration of our parallel filings will continue to yield significant patents, such as the new '719 patent announced just today," 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 318 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 recent acquisition of the patent assets from Nucleonics.

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 '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 '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).