Alnylam Receives new U.S. Patent Covering Small Interfering RNAs

Alnylam Pharmaceuticals, Inc. has announced that a new key fundamental patent from its exclusively held "Tuschl II" patent series was issued by the United States Patent and Trademark Office (USPTO).

The newly issued U.S. patent (U.S. Patent No. 7,078,196 or " '196 patent") broadly covers methods of making small interfering RNAs, the molecules that mediate RNAi, and includes 79 claims covering chemical modifications needed to introduce "drug-like" properties in RNAi therapeutics.

The issued patent is exclusively licensed to Alnylam for RNAi therapeutics on a worldwide basis through an agreement with Garching Innovation GmbH, the licensing agent for the Max Planck Society. 

The '196 patent further strengthens Alnylam's intellectual property (IP) leadership that includes another Tuschl II patent (U.S. Patent No. 7,056,704 or " '704 patent"), covering methods of making siRNAs to target any messenger RNA in a mammalian cell, and the recent outcome of the European Opposition Proceedings for the Kreutzer-Limmer I patent (EP 1144623 or " '623 patent"), where amended patent claims covering siRNAs with 15-21 base pairs were upheld.

"We are gratified that the USPTO has acknowledged the key inventions of Professor Thomas Tuschl performed at the Max Planck Institute in Gottingen," said Professor Peter Gruss, President of the Max Planck Society.

"This critical patent for RNAi therapeutics is owned by the Max Planck Society and has been licensed exclusively to Alnylam for commercialization."

"We are impressed with the progress Alnylam is making in its effort to develop innovative medicines using one of our Institute's most important scientific discoveries."

The new '196 patent is part of the research published in 2001 in the journal Nature by Thomas Tuschl, Ph.D., a founder of Alnylam.

In this seminal work performed at Max Planck, Professor Tuschl and his colleagues provided the published evidence that RNAi is mediated by small double-stranded RNAs with defined structural features and that synthetic siRNAs, with or without chemical modification, can be used to achieve RNAi in mammalian cells.

"This new patent extends what we believe is an unparalleled IP estate for RNAi therapeutics that includes over 150 patents issued in the world's largest pharmaceutical markets," said John Maraganore, Ph.D., President and Chief Executive Officer of Alnylam Pharmaceuticals.

"The '196 patent, together with other Alnylam-held IP assets, strengthens our continued efforts to create value through partnerships and license agreements with major pharmaceutical companies, biotechnology companies, and research product suppliers."

"Indeed, the unmatched strength of our patent estate supports a track record of business execution with over 20 current partners and licensees that have provided in excess of $100 million in funding to date, and a source of committed and sustainable funding for the future."

"Strategically, this important funding source for Alnylam supports our efforts to bring RNAi therapeutics to the market in a capital-efficient manner."

The 79 claims for the '196 patent cover the preparation of double-stranded RNAs having key structural elements that are widely recognized as critical requirements for the therapeutic activity of siRNAs, including:

- A double stranded region formed from two RNA strands of a length of 19-25 nucleotides; and,

- One or more 3'-overhangs at the ends of the double-stranded molecule.

The claims cover siRNAs with or without chemical modifications that are used to introduce certain drug-like properties into siRNAs such as stability and delivery.

The claims cover broad forms of such chemical modifications, including those of the 2' hydroxy position of the ribose backbone used to generate so-called "no-ribose" or "siNA" forms of RNAi therapeutics.

These chemical modifications include the use of phosphorothioate backbone linkages or 2'-0-methyl, and/or 2'-fluoro chemistries, irrespective of the percent of nucleotides modified and the extent of such modifications.

The new issued claims for U.S. Patent No. 7,078,196 will be made accessible on the Alnylam website. 

"It should become increasingly clear as patents issue in the field that Alnylam has assembled exclusive ownership of and access to critical IP needed for the development of RNAi drugs," said Robert Millman, Chief Intellectual Property Counsel of Alnylam.

"Because of the enablement and early priority date for the '196 patent, it is widely cited by patent offices across the world as prior art against later filed patent applications claiming chemically modified siRNAs."

In addition to the newly issued Tuschl II patent (U.S. Patent No. 7,078,196), Alnylam's IP estate includes issued or granted fundamental patents in the world's major pharmaceutical markets that claim the broad structural and functional properties of synthetic RNAi therapeutic products.

As it applies to the U.S. and EU alone, these include:

- The Tuschl II '704 patent (U.S. Patent No. 7,056,704) issued in June 2006, which broadly covers methods of making siRNAs to silence any and all disease targets;

- The Kreutzer-Limmer I '623 patent (EP 1144623) granted in August 2002, and upheld in June 2006, covering methods, medicaments, and uses of siRNAs having, among other structural features, a length of 15-21 base pairs;

- The Kreutzer-Limmer I '945 patent (EP 1214945) granted in June 2005, covering compositions, methods, and uses of siRNAs with a length between 15 and 49 nucleotides;

- The Kreutzer-Limmer II '061 patent (EP 1352061) granted in May 2006, covering compositions, methods, and uses of certain siRNAs and derivatives directed toward over 125 disease targets;

- Additional fundamental patents and patent applications licensed to Alnylam on an exclusive or non-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), and Glover et al. (EP 1230375); and,

- Several divisional patent applications pending of the aforementioned issued or granted patents and additional patent applications pending including Tuschl I.

In addition, Alnylam has a broad worldwide license for RNAi therapeutics from Isis Pharmaceuticals, Inc. for 150 issued patents pertaining to specific chemical modification of oligonucleotides used to introduce drug-like properties in siRNAs. These include:

- Phosphorothioate and 2'-O-methyl modifications (Buhr, U.S. Patent No. 6,473,205); and,

- 2'-Fluoro modifications (Cook, U.S. Patent Nos. 5,670,633; 6,005,087; and 6,531,584).

In addition to claims issued in '196 patent, Alnylam invites interested licensees to view issued or granted claims for other key Alnylam patents online.