Tag Archives: Pieter Cullis

Getting erased from the mRNA/COVID-19 story

Nathan Vardi’s August 17, 2021 article for Forbes magazine about Ian MacLachlan and the delivery system for mRNA vaccines tells a type of story I’ve more often seen in history books. It is reminiscent of the Thomas Edison and Nikola Tesla story of electricity. One gets all the glory while the other is largely forgotten.

I’m especially interested as much of this concerns players in the local (Vancouver, British Columbia, Canada) biotechnology scene. Vardi’s August 17, 2021 article sets the scene,

“The whole mRNA platform is not how to build an mRNA molecule; that’s the easy thing,” Bourla [Pfizer CEO Albert Bourla] says. “It is how to make sure the mRNA molecule will go into your cells and give the instructions.” 

Yet the story of how Moderna, BioNTech and Pfizer managed to create that vital delivery system has never been told. It’s a complicated saga involving 15 years of legal battles and accusations of betrayal and deceit. [emphases mine] What is clear is that when humanity needed a way to deliver mRNA to human cells to arrest the pandemic, there was only one reliable method available—and it wasn’t one originated in-house by Pfizer, Moderna, BioNTech or any of the other major vaccine companies. 

A months-long investigation by Forbes reveals that the scientist most responsible for this critical delivery method is a little-known 57-year-old Canadian biochemist named Ian MacLachlan. As chief scientific officer of two small companies, Protiva Biotherapeutics and Tekmira Pharmaceuticals, MacLachlan led the team that developed this crucial technology. Today, though, few people—and none of the big pharmaceutical companies—openly acknowledge his groundbreaking work, and MacLachlan earns nothing from the technology he pioneered. 

I have three stories (on this blog) mentioning Tekmira (all from 2014 or 2015) and none mentioning Protiva nor, for that matter, Ian MacLachlan.

Back to Vardi’s August 17, 2021 article,

Moderna Therapeutics vigorously disputes the idea that its mRNA vaccine uses MacLachlan’s delivery system, and BioNTech, the vaccine maker partnered with Pfizer, talks about it carefully. Legal proceedings are pending, and big money is at stake. 

Moderna, BioNTech and Pfizer are on their way to selling $45 billion worth of vaccines in 2021. They don’t pay a dime to MacLachlan. Other coronavirus vaccine makers, such as Gritstone Oncology, have recently licensed MacLachlan’s Protiva-Tekmira delivery technology for between 5% and 15% of product sales. MacLachlan no longer has a financial stake in the technology, but a similar royalty on the Moderna and Pfizer-BioNTech vaccines could yield as much as $6.75 billion in 2021 alone. …

Vardi provides evidence (Note: A link has been removed from the August 17, 2021 article excerpt,

Despite their denials, scientific papers and regulatory documents filed with the FDA [US Food and Drug Administration] show that both Moderna and Pfizer-BioNTech’s vaccines use a delivery system strikingly similar to what MacLachlan and his team created—a carefully formulated four-lipid component that encapsulates mRNA in a dense particle through a mixing process involving ethanol and a T-connector apparatus. 

For years, Moderna claimed it was using its own proprietary delivery system, but when it came time for the company to test its Covid-19 vaccine in mice, it used the same four kinds of lipids as MacLachlan’s technology, in identical ratios. 

According to Vardi’s LinkedIn profile: “I am a senior editor at Forbes, where I am responsible for the coverage of hedge funds, private equity, and other big investors. I lead investigative reporting efforts and have written 20 cover stories for Forbes Magazine,” he does not appear to have any medical or bioscience expertise (Bachelor of Journalism from Carleton University [Canada] and Masters of International Affairs from Columbia University [US].) Presumably someone he consulted or someone on his team provided the skills necessary for analyzing the scientific papers and documents.

You may recognize this scientist (from the August 17, 2021 article),

Not everyone ignores MacLachlan. “A lot of credit goes to Ian MacLachlan for the LNP [lipid nanoparticle],” says Katalin Karikó, [emphasis mine] the scientist who laid the groundwork for mRNA therapies before joining BioNTech in 2013. But Karikó, now a frontrunner for a Nobel Prize, is angry that MacLachlan didn’t do more to help her use his delivery system to build her own mRNA company years ago. “[MacLachlan] might be a great scientist, but he lacked vision,” she says.

I have more about Karikó and her role in the mRNA vaccine story here in a March 5, 2021 posting.

As for MacLachlan’s start (from the August 17, 2021 article),

… With a Ph.D. in biochemistry, MacLachlan joined Inex in 1996, his first job after completing a postdoctoral fellowship in a gene lab at the University of Michigan. 

Inex was cofounded by its chief scientific officer, Pieter Cullis, now 75, a long-haired physicist who taught at the University of British Columbia. From his perch there Cullis started several biotechs, cultivating an elite community of scientists that made Vancouver a hotbed of lipid chemistry. 

As companies rise and fall with intellectual property being assigned to one company or other, legal brawls ensue. This was the time that Karikó came knocking on the door, from the August 17, 2021 article,

It was in the midst of all this furious legal fighting that Hungarian biochemist Katalin Karikó first showed up at MacLachlan’s door. Karikó was early to grasp that MacLachlan’s delivery system held the key to unlocking the potential of mRNA therapies. As early as 2006, she began sending letters to MacLachlan urging him to encase her groundbreaking chemically altered mRNA in his four-lipid delivery system. Embroiled in litigation, MacLachlan passed on her offer. 

Karikó didn’t give up easily. In 2013, she flew to meet with Tekmira’s executives, offering to relocate to Vancouver and work directly under MacLachlan. Tekmira passed. “Moderna, BioNTech and CureVac all wanted me to work for them, but my number one choice, Tekmira, didn’t,” says Karikó, who took a job at BioNTech in 2013. 

By this time, Moderna CEO Stéphane Bancel [emphasis mine] 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 up front, plus royalties, to strike a deal.

Instead, Moderna partnered with Madden [Thomas Madden], who was still working with Cullis at their drug delivery company, Acuitas Therapeutics.  …

I have been wondering why Acuitas Therapeutics hasn’t been getting all that much attention in the hyperbolic discussions about British Columbia’s (or Vancouver’s) thriving biotechnology scene. (I’ll have more about the ‘scene’ in a later posting.) Perhaps all this legal wrangling is not considered helpful when bragging. (I do have a November 12, 2020 post, which features Acuitas, an interview with its president and chief executive office Dr. Thomas Madden, and an explanation of their technology.)

As for Moderna, I have a special interest as the company has announced plans to open a production facility here in Canada and one of Moderna’s founders is Canadian, Derek Rossi. (He too is mentioned in the March 5, 2021 posting, scroll down to the ‘Entrepreneurs rush in’ subhead; he is not an altogether happy camper.)

Rossi has opinions on how we should be doing things here as noted in a June 17, 2021 article by Barbara Shecter for the Financial Post (Moderna founder says Canada needs to build a biotech hub to avoid ‘getting caught with its pants down next time’). Thank you, Mr. Rossi. (I’m more familiar with clusters than hubs [hubs were a popular topic of conversation about 20 years ago but in Canada we seem more interested in clusters; see John Newbigin’s “Hubs, clusters and regions” on britishcouncil.org for a description of the differences].)

As for Moderna’s response to all of the legal wrangling over mRNA delivery systems, from Vardi’s August 17, 2021 article,

Moderna pursued a different strategy. It filed lawsuits with the U.S. Patent and Trademark Office seeking to nullify a series of patents related to MacLachlan’s delivery system, now controlled by Genevant. But in July 2020, as Moderna was pushing its vaccine through clinical trials, an adjudicative body largely upheld the most important patent claims. (Moderna is appealing.)

I highly recommend reading Vardi’s August 17, 2021 article as I have not done justice to all of the ‘ins and outs’ of the story.

You can see how thoroughly MacLachlan has been erased form the lipid nanoparticle delivery system/COVID-19 vaccine story in this May 24 ,2021 posting (Lipid nanoparticles: The underrated invention behind the vaccine revolution) by Nada Salem at the Science Borealis blog. It is largely a description of the technology and in the last two paragraphs a history of its development with no mention of MacLachlan or any of his companies.

One last thought, I wonder how Vardi found out about MacLachlan. Could someone have brought the story to his attention and who might that have been?

Why is Precision Nanosystems Inc. in the local (Vancouver, Canada) newspaper?

Usually when a company is featured in a news item, there’s some reason why it’s considered newsworthy. Even after reading the article twice, I still don’t see what makes the Precision Nanosystems Inc. (PNI) newsworthy.

Kevin Griffin’s Jan. 17, 2021 article about Vancouver area Precision Nanosystems Inc. (PNI) for The Province is interesting for anyone who’s looking for information about members of the local biotechnology and/or nanomedicine community (Note: Links have been removed),

A Vancouver nanomedicine company is part of a team using new genetic technology to develop a COVID-19 vaccine.

Precision NanoSystems Incorporated is working on a vaccine in the same class the ones made by Pfizer-BioNTech and Moderna, the only two COVID-19 vaccines approved by Health Canada.

PNI’s vaccine is based on a new kind of technology called mRNA which stands for messenger ribonucleic acid. The mRNA class of vaccines carry genetic instructions to make proteins that trigger the body’s immune system. Once a body has antibodies, it can fight off a real infection when it comes in contact with SARS-CoV-2, the name of the virus that causes COVID-19.

James Taylor, CEO of Precision NanoSystems, said the “revolutionary technology is having an impact not only on COVID-19 pandemic but also the treatment of other diseases.

The federal government has invested $18.2 million in PNI to carry its vaccine candidate through pre-clinical studies and clinical trails.

Ottawa has also invested another $173 million in Medicago, a Quebec-city based company which is developing a virus-like particle vaccine on a plant-based platform and building a large-scale vaccine and antibody production facility. The federal government has an agreement with Medicago to buy up to 76 million doses (enough for 38 million people) of its COVID-19 vaccine.

PNI’s vaccine, which the company is developing with other collaborators, is still at an early, pre-clinical stage.

Taylor is one of the co-founders of PNI along with Euan Ramsay, the company’s chief commercial officer.

The scientific co-founders of PNI are physicist Carl Hansen [emphasis mine] and Pieter Cullis. Cullis is also board chairman and scientific adviser at Acuitas Therapeutics [emphasis mine], the UBC biotechnology company that developed the delivery system for the Pfizer-BioNTech COVID-19 vaccine.

PNI, founded in 2010 as a spin-off from UBC [University of British Columbia], focuses on developing technology and expertise in genetic medicine to treat a wide range of infectious and rare diseases and cancers.

What has been described as PNI’s flagship product is a NanoAssemblr Benchtop Instrument, which allows scientists to develop nanomedicines for testing.

It’s informational but none of this is new, if you’ve been following developments in the COVID-19 vaccine story or local biotechnology scene. The $18.2 million federal government investment was announced in the company’s latest press release dated October 23, 2020. Not exactly fresh news.

One possibility is that the company is trying to generate publicity prior to a big announcement. As to why a reporter would produce this profile, perhaps he was promised an exclusive?

Acuitas Therapeutics, which I highlighted in the excerpt from Griffin’s story, has been featured here before in a November 12, 2020 posting about lipid nanoparticles and their role in the development of the Pfizer-BioNTech COVID-19 vaccine.

Curiously (or not), Griffin didn’t mention Vancouver’s biggest ‘COVID-19 star’, AbCellera. You can find out more about that company in my December 30, 2020 posting titled, Avo Media, Science Telephone, and a Canadian COVID-19 billionaire scientist, which features a link to a video about AbCellera’s work (scroll down about 60% of the way to the subsection titled: Avo Media, The Tyee, and Science Telephone, second paragraph).

The Canadian COVID-19 billionaire scientist? That would be Carl Hansen, Chief Executive Officer and co-founder of AbCellera and co-founder of PNI. it’s such a small world sometimes.

Canadian Space Agency funds nanomedicine?

I suppose it’s ignorance but I can’t quite fathom why the Canadian Space Agency (CSA) [ETA March 17, 2011: Corrected the mane of the Agency from Canada Space Agency to Canadian Space Agency] is partnering with the Canadian Institutes of Health Research (CIHR) to fund nanomedicine. I don’t understand how that fits into the CSA’s mandate. The March 16, 2011 news item on Nanowerk doesn’t answer my questions,

Research on nanomedicine and regenerative medicine is designed to prevent disease and improve human health. Nanomedicine delivers medical technologies that detect or function at the molecular level to diagnose and treat disease, while regenerative medicine stimulates the renewal of bodily tissues and organs or restores function through natural and bioengineered means. Various innovations in these areas have helped combat vascular diseases, cancer, diabetes, multiple sclerosis and other chronic diseases. By promoting research in these areas, CIHR and CSA will be moving Canada to the forefront of modern medical research. [emphasis mine]

When was the Space Agency mandated to bring Canada to the “forefront of modern medical research?” I did look at the projects to see if any of them might have a ‘space travel’ component,

This funding will enable researchers to potentially:

# Identify microlesions in multiple sclerosis, using a new tool for quantifying the cause of the disease and how well a treatment is working, Dr. Daniel Côté, Université Laval;

# Create personalized nanomedicines that silence cancer-causing genes, Dr. P[ieter] Cullis, University of British Columbia;

# Develop microchip-based devices to analyze prostate cancer markers in blood, Dr. Shana Kelley, University of Toronto;

# Generate transplantable, insulin-producing cells from stem cells for diabetes, Dr. Timothy Kieffer, University of British Columbia;

# Develop innovative sensorimotor rehabilitation approaches for patients with spinal cord injuries or stroke, Dr. Serge Rossignol, Université de Montréal;

# Study how novel therapeutic interventions can regenerate blood vessels, Dr. Michael Sefton, University of Toronto; and,

# Develop nanotechnology-enabled image-guided methods of diagnosing and treating lung cancer and vascular diseases, Dr. Gang Zheng, University Health Network.

I suppose the project to regenerate blood vessels might have some applications appropriate for space travel/exploration but the rest leave me puzzled. If anyone has an answer or even a guess, please do leave a comment.

ETA March 17, 2011: I found the CSA’s mandate here,

The mandate of the Canadian Space Agency is:

To promote the peaceful use and development of space, to advance the knowledge of space through science and to ensure that space science and technology provide social and economic benefits for Canadians.