Meet Covid's forgotten hero:
Mighty Minnow: Acuitas Therapeutics CEO Thomas Madden, MacLachlan’s scientific rival, in his Vancouver lab. His company may be small and private, but its impact has been enormous. In 2020, its 30 employees worked around the clock on the delivery system for the Pfizer-BioNTech mRNA vaccine.show their vaccine uses the same four kinds of lipids in nearly the exact ratios that MacLachlan and his team patented years ago, albeit with one of those lipids being a new proprietary variation.
The exchange gave MacLachlan a bad feeling. So did the presence of a former colleague, Thomas Madden, who had been fired by Tekmira five years earlier. By this point MacLachlan had spent more than a decade working on his delivery system, yet people like Bancel seemed more interested in working with the London-born Madden.
“We assembled all the LNP [lipid nanoparticle] pieces at Inex, but we didn’t get it to work” for genetic material, Cullis says. The team he led quickly went on to develop a new lipid nanoparticle made of four specific kinds of lipids. Though these were among the lipids Inex had also been using in its experiments, MacLachlan’s LNP had a dense core that differed significantly from the sac-like liposome bubbles developed by Inex. MacLachlan’s team had figured out the specific ratios of the four kinds of lipids that worked best relative to one another. Everything was dutifully patented.
show Alnylam used MacLachlan’s delivery system for Onpattro—with one exception. For one of the four kinds of lipids, Alnylam used a modified version it developed with Thomas Madden. Mark Murray, the CEO MacLachlan had recruited to run Protiva, stood in a room at Tekmira Pharmaceuticals, a small publicly traded shell company he had just taken over.
That round of the legal brawl was settled in 2012, with Alnylam paying Tekmira $65 million and agreeing to assign dozens of its patents back to Tekmira. Those patents included ones for the improved lipid that Madden had developed for Onpattro. Under the deal, Cullis and Madden’s new company was granted a narrow license to use the MacLachlan delivery system to create new mRNA products from scratch.
By this time, Moderna CEO Stéphane Bancel was also trying to solve the delivery puzzle. Bancel held discussions with Tekmira about collaborating, but talks stalled. At one point, Tekmira indicated it wanted at least $100 million upfront, plus royalties, to strike a deal. Then Madden’s company, Acuitas, sublicensed the delivery technology to Moderna for the development of an mRNA flu vaccine. Murray was confident Madden had no right to do so, and in 2016 he gave notice that he intended to terminate Acuitas’ licensing agreement. Per custom, two months later, Acuitas sued in Vancouver, denying that it had violated any deal. On cue, Murray countersued, initiating a fresh round of legal combat. Importantly, though, this batch of lawsuits directly involved mRNA.
After the Moderna and Pfizer-BioNTech vaccines were authorized, Drew Weissman, a prominent mRNA researcher at the University of Pennsylvania,that both use delivery systems that are “similar to the Alnylam Onpattro product” but with a proprietary version of one of the lipids. Weissman noted both companies were using T-junction mixing.
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