RNAi Litigation

I went to the Suffolk County Superior Courthouse on Pemberton Square in downtown Boston this week. The experience inside the building reminded me of the early 1990’s when I would wander over to the Lane Medical Library at Stanford to look for research papers of interest without the help of the Internet. As far as I can tell there is no useful Internet site where one can download Superior Court documents like PACER where all documents are available for Federal cases. Tekmira filed its lawsuit against Alnylam in March in the Business Litigation Session of the Suffolk County Superior Court accusing Alnylam of stealing their RNAi delivery technology.

I went up to the 12th floor to find the file for this case. After looking through the cabinet that holds all the case files, the clerk went upstairs and found the case file in one of the cubicles where you could sit and read to your heart’s delight. Apparently this case is a big deal because the file, a thick folder and a box of exhibits, is left out on a table.

It would have been an impossible task for me to read through all of the papers because of another commitment (and my real job) so I focused in on Alcana Technologies’ response to Tekmira’s amended complaint. I learned also that a hearing was scheduled in October which I will try to attend.

PART 2 will follow tomorrow

The Background of this case against Alnylam and partner, Alcana in Vancouver British Columbia

In 2006, Alnylam Pharmaceuticals (“Alnylam”) began collaborating with Tekmira Pharmaceuticals and Protiva Biotherapeutics (referred to here as “Tekmira”) on research regarding certain lipid carriers for delivery of Alnylam’s proprietary siRNA compounds. siRNA can be used as therapeutic agents by acting to interfere with or silence disease-carrying genes. One difficulty in administering siRNA is developing ways to effectively get the compounds to the place in the body where they can be most effective without causing unwanted side-effects. The purpose of the Alnylam collaboration with Tekmira was to investigate the suitability of certain novel lipid nanoparticles (“LNPs”) or stable nucleic acid lipid particles (“SNALP”) as a means of administering Alnylam’s siRNAs.

Alnylam entered into collaboration agreements with Tekmira (Tekmira and Protiva) detailing the scope of their research programs and each company’s rights and obligations in intellectual property developed in the course of their research conducted under these agreements.

Following the execution of an Initial License and Collaboration Agreement in January 2007 between Tekmira and Alnylam, the two companies formed a joint agreement to engage in collaborative research regarding lipid carriers and siRNA delivery. Under this collaborative research program, Tekmira formed a team of scientists led by Dr. Thomas Madden, called the “Alnylam Research Group” to work with a similar team within Alnylam.

Tekmira’s technology

During the period from January 2007 to October 2008, the Alnylam Research Group undertook the synthesis and testing of cationic lipids to identify molecules with improved properties as a part of its collaborative research with Alnylam.

The research focused on a class of cationic lipids referred to by the designation “DLin-K-DMA.” The Alnylam Research Group synthesized and tested many variations of these compounds, also known as “K-series” lipids. In the course of this research, the team discovered that adding a second carbon atom to the linker group of the molecule to form DLin-K-C2-DMA resulted in significant improvements in potency. Notably, the further addition of carbon atoms to the linker group – e.g., to produce DLin-K-C3-DMA or DLin-K-C4-DMA – resulted in loss of activity compared to DLin-K-C2-DMA. Based on these experiments, the team concluded that the most active linker group within the K-series lipids consisted of two carbon atoms.

The research program resulted in two patent applications by Tekmira (WO 2009 086558 and WO 2010 042877). The ‘887 application disclosed the chemical structure of the K-series lipids and data reflecting their activity, in particular, the superior potency of DLin-K-C2-DMA (referred to as “KC2”). The data contained in the patent application demonstrated that KC1 and KC2 showed the highest potency within the K-series class of LNPs tested by the Alnylam Research Group.

In addition to the K-series lipids, the Alnylam Research Group also experimented with a number of other cationic lipids. One of these compounds was referred to as DLin-M-DMA. This lipid was structurally similar to the K-series except that it did not contain a ketal group characteristic of the K-series (this lipid became known as an M-series lipid).The structure of this particular M-series lipid was disclosed publicly in the ‘877 Application. Like KC2, DLin-M-DMA contained a two-carbon linker (referred to as “MC2”) because that was the optimal linker length they had identified with the K-series lipids.

Upon information and belief, Tekmira did not synthesize or evaluate any M-series lipids, nor did it proceed with further development of MC2, which was less active than the K-series lipids.

Tekmira merges with Protiva and fires the Alnylam Research Group

While the Alnylam Research Group was continuing its research on the synthesis and testing of cationic lipids in collaboration with Alnylam, Tekmira merged with Protiva in May of 2008. Following the merger, former Protiva executives, Dr. Mark Murray and Dr. Ian MacLauchlan exercised executive control of the merged company, as CEO and CSO, respectively.

For several months after Tekmira merged with Protiva, the two companies kept their activities strictly separate as a result of contractual obligations to third parties. This period, known as the “Restriction Period,” ran from May 30, 2008, through October 9, 2008.

At the end of the Restriction Period, the members of the Alnylam Research Group, who had been long time employees of Tekmira, were abruptly and without reason fired by Tekmira.

On or about October 9, 2008, Tekmira filed patent applications in the USPTO reflecting the work conducted by the Alnylam Research Group. Those applications were ultimately published on April 15, 2010 as part of the ‘877 Application (not clear what is being said here, JL). Among other things, the ‘877 application published the data reflecting the superior potency of the KC2 lipid. It also disclosed the MC2 structure. By virtue of its publication, the information in the ‘877 Application does not and cannot constitute trade secrets (Tekmira claims that Alnylam stole trade secrets).

Ex-Tekmira Employees form Alcana Technologies

Tekmira’s abrupt termination of the employment of the principal scientists who had been working with Alnylam signaled that Tekmira was not interested in continuing the work that it had conducted through their Alnylam Research Group. Alnylam was, however, interested in engaging the now- unemployed ex-Tekmira employees including Madden, Chen Tam, Mui, and Hope, to continue their efforts to develop novel LNPs suitable for use in delivering siRNA therapeutics.

In late January 2009, each of this group together with Dr. Steven Ansell (collectively the “Consultants”) entered into consulting agreements with Alnylam (“Consulting Agreements”). Under these agreements, the Consultants expressly agreed not to use the confidential information or trade secrets of any third parties in their research. From the outset of their work, the Consultants were aware of their obligations not to use any confidential information of Tekmira and were careful not to do so

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