RNAi Litigation

Archive for July, 2010

See Dirk Haussecker’s summary of the latest Alnylam/Tekmira developments with SNALP here.

In March of 2007 Alnylam and Inex Pharmaceuticals formed an alliance in which Alnylam took a worldwide exclusive license to Inex’s lipid-based siRNA delivery formulations. This deal with Inex was in exchange for access to Alnylam’s IP for oligonucleotide drugs that act through immune stimulation (not RNAi drugs) as well as the right to develop three RNAi drugs based on Alnylam’s IP. In May of 2007 Inex became Tekmira and later coined the term SNALP (stable nucleic acid lipid particle) for their delivery system. SNALP essentially comprises a nucleic acid encapsulated by cationic and fusogenic lipids, all of which are surrounded by a polyethylene glycol coating. Today SNALP is considered one of the better siRNA delivery vehicles and the three-year partnership between Alnylam and Tekmira appears to be strong. [See Dirk Haussecker’s discussion on the promise of SNALP and future prospects for Tekmira.].

Two years earlier on February 1, 2005, Sirna Therapeutics and Protiva formed a strategic alliance in which Sirna purportedly acquired rights to the SNALP technology which Protiva claimed to own (Protiva was spun out of Inex). Then Protiva sued Inex for passing the word in the RNAi industry that Protiva did not own the IP covering SNALP for delivery of RNAi. According to Inex in a countersuit against Protiva, Protiva was granted only limited rights to the SNALP technology which did not include RNAi applications.

Sirna Therapeutics also filed a lawsuit against Protiva with the following allegations:

Allegation 16 – “Throughout the parties’ negotiation of the Strategic Alliance Agreement, prior to the execution of the agreement, Protiva officers and employees represented to Sirna’s representatives that Protiva fully controlled and owned the intellectual property rights (for SNALP) that Protiva was negotiating to license to Sirna pursuant to the Strategic Alliance Agreement.”

Allegation 21 – “In reliance upon the representations of Protiva …, Sirna executed the Strategic Alliance Agreement … (a $1 M deal).”

Allegation 26 - … “Protiva representatives…acknowledged in subsequent correspondence with Inex prior to execution of the Strategic Alliance Agreement that Protiva needed to acquire a license from Inex for such intellectual property.” Read the rest of this entry »

Today from Case 1:09-cv-11116-PBS Document 396 Filed 07/26/10

Below are Judge Saris’ statements with the references to other court decisions removed:

Max Planck claims that Whitehead breached a fiduciary duty when it misused the Tusch1 II information during the prosecution of Tusch1 I patent applications. Whitehead contends that any fiduciary duty arises as a result of the parties’ contractual relationship and, as such, the Agreements’ damages-limiting provisions apply also to the breach of fiduciary duty claim. The Court has ruled previously that the 2001 and 2003 Agreements bar recovery of “consequential” and “incidental” damages recoverable on Max Planck’s breach of contract claim.

Whitehead’s argument is persuasive. Where a fiduciary relationship arises out of a contract, the obligations are defined and limited by the terms of that contract, not by general fiduciary principles.

A clause releasing a fiduciary from liability for breach of fiduciary duties is valid “unless the clause purports to include breaches committed intentionally, in bad faith, or with reckless indifference to the interests of the beneficiary of those duties.”

Here, the fiduciary duty plaintiffs allege arises primarily from the contractual relationships, and so is limited by the contract terms.

The contractual damages limitation clause in the 2001 Agreement provides:

In no event shall the joint owners . . . be liable for incidental or consequential damages of any kind, including economic damages or injury to property and lost profits, regardless of whether the joint owners shall be advised, shall have other reason to know, or in fact shall know of the possibility of the foregoing.

The 2003 Agreement has a similar provision. Alnylam entered into a related 2002 co-exclusive license agreement with Max Planck, approved by Whitehead and MIT. Both consented to be bound by the 2002 agreement. Read the rest of this entry »

Today from Case 1:09-cv-11116-PBS Document 396 Filed 07/26/10

Below are Judge Saris’ statements with the references to other court decisions removed:

The second issue is whether plaintiffs’ equitable claims for unjust enrichment are barred by the statute of limitations. “In Massachusetts, the statutes of limitation applicable to law actions based on contract and tort are also applicable to suits in equity.” “Under Massachusetts law, the determination of whether the contract or tort statute of limitations applies is controlled by the essential nature of a party’s claim.” A claim sounding in tort is subject to a three year statute of limitations, while one sounding in contract is subject to a six year limitations period. (Mass. Gen. Laws)

UMass’s Motion to Dismiss Count VI

Plaintiffs’ Count VI alleges unjust enrichment through “wrongful use of the Tuschl II invention” to broaden the Tuschl I applications to plaintiffs’ detriment.

The nature of plaintiffs’ claim is unclear. The core allegation is that Whitehead and UMass engaged in a secret strategy to “appropriate for . . . themselves the commercial value of the Tuschl II invention,” a claim that effectively is one for conversion. (“Where, as here, the unjust enrichment claim is premised on an alleged conversion, and not on a breach of contract, the tort statute of limitations applies.”).

The First Amended Complaint also asserts, however, that Whitehead assumed a contractual obligation of good faith regarding the use of the Tuschl II information. (“A six-year statute of limitations also applies to unjust enrichment claims based on the same underlying facts … applying six year limitations period where, although plaintiff’s unjust enrichment claim did “rest in part on the circumstances of the alleged conversion, it also arises from the breach of contract allegations”).

To the extent Max Planck’s claims of unjust enrichment rest even in part on the breach of contract allegations, they are not time-barred. To the extent the claims against Whitehead are conversion-based, however, they are barred by the three years limitation period.

All of the claims against UMass are governed by a three year statute of limitations. Therefore regardless of the nature of the claim in Count VI, it is time-barred. Read the rest of this entry »

Today from Case 1:09-cv-11116-PBS Document 396 Filed 07/26/10

Judge Saris: “Because plaintiffs seek general damages caused by the breach of fiduciary duty and breach of contract claims against Whitehead, the Motion to Strike Plaintiffs’ Jury Demand is DENIED. I adopt Judge Dein’s report and recommendation regarding Whitehead’s motion. I strike the jury demand on the claims against UMass, however, on the ground that the only claims remaining are equitable (unjust enrichment and Chapter 93A), and that neither party has sought a jury trial on UMass’s counterclaims.”

Further explanation of the Judge’s decisions will be posted shortly. See above.

Previously Judge Saris made the following rulings on motions to dismiss by Whitehead in Docket 389:
Count I (Breach of Contract) – dismissal DENIED.
Count II (Breach of the Implied Covenant of Good Faith and Fair Dealing) – dismissal DENIED.
Count III (Breach of Fiduciary Duty) – dismissal DENIED.
Count VII (misuse of the Tuschl II information under Mass. Gen. Laws ch. 93A) - dismissal DENIED.
Count VIII (declaratory judgment claim with respect to the ownership of the Tuschl II material) - dismissal DENIED.

and

Previously Judge Saris made the following rulings on motions to dismiss by UMass in Docket 390:

Count VII (violations of Mass. Gen. Laws Ch. 93A) - dismissal DENIED.
Count VIII (declaratory judgment) - dismissal DENIED.

Furthermore,

“Counts XVII (Ch. 93A) and XVIII (declaratory judgment) are not dismissed insofar as they pertain to the Sirna license.”

Today from Case 1:09-cv-11116-PBS Document 396 Filed 07/26/10

“Defendants have moved to dismiss the First Amended Complaint. The Court has issued two memoranda and orders on those motions, with which it assumes familiarity. (Docket Nos. 389 and 390.) After hearing and supplemental briefing, the Court now rules on the remaining issues as follows:”

“ORDER: Defendants’ Motion to Strike Plaintiffs’ Jury Demand [Docket No. 109] is DENIED as to Whitehead, but ALLOWED as to the claims against UMass.

With respect to the unjust enrichment claim, Whitehead’s Motion to Dismiss [Docket No. 185] Count VI is DENIED insofar as the claim sounds in contract. UMass’s Motion to Dismiss [Docket No. 182] is ALLOWED with respect to Count VI, but DENIED as to Count XV.”

So Count VI (Unjust Enrichment) against Whitehead and Count XV (Unjust Enrichment) against UMass remain and there will be a jury trial. The Max-Planck can seek “general damages” from Whitehead for costs like attorneys’ fees.

Sirna Therapeutics filed its first patent application (US 20050124566) on this use of siRNA in June of 2004. After being acquired by Merck & Co. in late 2006, Sirna filed a second related application (US 20090099117) in April of 2009.

We are still waiting for rulings by Judge Saris.

As the 2008 Olympics in Beijing were gaining momentum, the subject of doping made its way into the news coverage. Today the next Olympics in London is just two years away in 2012. The prevalence of doping among athletes in professional, college and high school sports is well documented. And up until now, doping has always involved muscle-enhancing drugs such as steroids and recombinant growth factors.

Growth factors such as Human Growth Hormone and other new age drugs result from recombinant DNA technologies of the mid-1980s that a decade later led to drugs approved for human use to treat growth deficiencies.

In theory, these same growth-promoting drugs could be introduced into humans using gene therapy. However, gene therapy has been notoriously difficult to control, and once you introduce the gene, how do you take it back after its effect is no longer needed? After all, modern athletes who wish to cheat the system to achieve their athletic goals may wish to return to a normal life after athletic ambitions have been satisfied. With gene therapy there may be no way to reverse the unending effects of alien muscle-enhancing genes.

However, a new genetic solution has emerged that may solve the problem of uncontrollable long-term effects and offer a new, easier way to cheat the system.

In a 2004 Scientific American (July issue) article titled, “Gene Doping,” H. Lee Sweeney describes the “Belgian Blue Bull” as the bovine version of the Incredible Hulk. The Belgian Blue Bull is a freak of nature because an inherited genetic mutation in the breed deactivates both copies of the gene that encodes myostatin, a protein that inhibits muscle growth so the organism can maintain a balance between muscles and skeleton. The absence of this protein not only allows unchecked muscle growth, it also inhibits fat deposition. As a result, this bull has incredible lean muscle bulk—a bigger, stronger, and, yes, faster bull.

In a more recent paper in Trends in Genetics entitled “Sprinting without myostatin: a genetic determinant of athletic prowess,” author Se-Jin Lee of Johns Hopkins University (and has been a paid consultant of Merck) describes the occurrence of this myostatin mutation in mice, sheep and bully whippet racing dogs (Lee SJ Trends Genet. 23:475-477, 2007). In whippets, mutations in both copies of the myostatin gene lead to a dog with twice as much muscle mass. A mutation of only one copy of the myostatin gene results in about a 25 percent increase in muscle bulk with increased athleticism.
Read the rest of this entry »

In June 2009 the Max Planck Society (Max Planck) and Alnylam Pharmaceuticals (Alnylam) filed a multiple-count complaint against Massachusetts Institute of Technology (MIT), the Whitehead Institute for Biomedical Research (Whitehead), and the University of Massachusetts (UMass) that questions the legality of several business dealings among the parties as well as the intellectual property (IP) rights to seminal small interfering RNA (siRNA) technologies. MIT has since been dismissed from this case.

The discovery of efficient RNA interference by small synthetic double-stranded RNA molecules (siRNA) has begun to revolutionize the pharmaceutical industry after only nine years. Prior to this invention only a low percentage of gene products could be targeted effectively with drugs. These conventional targets were preferably proteins on the cell surface such as receptors of growth signals. One of many examples of this type of drug target is the growth factor receptor targeted by the successful anti-cancer drug, Herceptin (antibody), developed by Genentech. By contrast and in theory, therapeutic siRNA molecules can silence any of 20,000 potential gene targets. Thus, as a result of this new technology all genes either individually or in combination can be ‘drugable’ rather than one or two thousand at most.

The invention of siRNA by Thomas Tuschl and colleagues at the Max-Planck Institute in Goettingen, Germany - was first publicly disclosed in the journal Genes and Development on January 15, 2001. A second paper by Tuschl and colleagues was published in the widely circulated journal, Nature, on May 24, 2001, demonstrating for the first time that even human genes could be silenced by the Tuschl method.

Before these two publications, molecular biologists had spent decades trying to figure out how to block gene expression of individual genes with synthetic, potentially therapeutic RNA or DNA molecules. The idea here was to take advantage of the fact that single-stranded RNA or DNA polynucleotides complimentary in nucleotide sequence (according to Watson-Crick nucleotide base pairing) to a messenger RNA (mRNA) can form hybrids with any matched target mRNA to block synthesis of the protein encoded by that target mRNA. Since the nucleotide sequence of each mRNA is unique for the protein product it produces, this approach to blocking gene expression should be specific for any target gene that controls disease(s) caused by aberrant cellular gene expression (cancer, genetic diseases, etc.), or diseases caused by infectious viral or microbial pathogens.

One measure of perceived value of the siRNA technology is the fact that nearly every big pharma company has invested $100s of millions if not the promise of billions of dollars to acquire rights to this technology. For example, in December 2006 Merck & Co. purchased Sirna Therapeutics (then in Boulder CO, now in South San Francisco CA) spending $1.2 billion; and in July 2007 Hoffmann-La Roche formed a partnership with Alnylam Pharmaceuticals (Cambridge MA) at a cost of $331 M with the potential for over $1 B in investment if benchmarks were met. Read the rest of this entry »

See Dirk Haussecker’s piece entitled “Upcoming $100M Novartis Decision to Shake Up RNAi Therapeutics” involving Alnylam.