Week 41: Nobel Prize awarded to Frances Arnold, new application of CRISPR-Cas9, and the veterinary industry faces paradigm shift

Posted on October 19, 2018 in Uncategorized

Week #41 in the News

Nobel Prize awarded to researchers behind enzyme tech that gave us Humira

This year’s Nobel Prize for Chemistry was awarded to researchers whose work on enzymes has directly resulted in the development of some of the world’s best-selling biologic drugs.

The chemistry gong was shared by Frances Arnold from the California Institute of Technology in Pasadena, George Smith of the University of Missouri in Columbia and Gregory Winter of the UK Medical Research Council’s Laboratory of Molecular Biology in Cambridge.

Arnold was awarded half of the £770,000 prize for work on “directed evolution” of enzymes, while Smith and Winter shared the remainder for their work using viruses and bacteria to direct the evolution of proteins.

All three fields of research have application in the improvement of therapeutic antibody based drugs according to the Nobel panel, which said “The uses of Frances Arnold’s enzymes include more environmentally friendly manufacturing of chemical substances, such as pharmaceuticals, and the production of renewable fuels for a greener transport sector.”

The panel also pointed out that techniques developed by Winter were used to develop Humira (adalimumab). The Guardian spoke with to the scientist, who shared his experiences of how his work had directly helped cancer patients.

Reuters described the award-winning research as a “paradigm shift” that has revolutionized everything from disease treatment to drug production, via industrial chemistry.

Research news

Mice have same-sex parents as CRISPR and stem cell research shows promise. In this case, the scientists have used stem cells and the gene editing technique CRISPR to breed mice from genetic material provided by two male mice. However, none of the bipaternal pups survived to adulthood.

According to the authors, the study, which was published in Cell last week, is the first to show “the factors necessary for crossing same-sex reproduction barriers in mammals.”

GEN also covered the part of the research where pups were bred pups material take from two female mice. These bimaternal pups survived to adulthood and were able to reproduce normally.

The significance of the research, according to STAT, is that it improves our understanding of a process called genomic imprinting, a process that ensures progeny have both paternal and maternal DNA.

Mammalian genomes have two copies of each gene, one from the father and one from the mother, both of which are usually expressed. Both copies are needed for viability, however, for certain genes only one copy is expressed while the other is inactive.

For example, usually only the paternal copy of the gene IGF2 – which controls growth – is active. The maternal copy of IGF2 is inactive.

While any human therapeutic application of the approach is a very long way off – even if the huge ethical considerations are ignored – the researchers say the findings have brought us closer to understanding how imprinting works and more generally how gene activity is controlled.

More on CRISPR from GEN…

Swiss scientists from ETH Zurich have used an enhanced CRISPR-Cas editing method in mice to correct a gene mutation that causes phenylketonuria (PKU). PKU is an autosomal recessive disease that inhibits the metabolism of amino acid, phenylalanine. The long-term implications of PKU and the buildup of phenylalanine in the body can cause long term health implications, such as seizures, prompting some countries to screen infants for PKU. The researchers indicate that the evidence found could reverse this disease in humans, with 60% of hepatocytes being corrected in the mouse model.

The study utilized an adeno-associated viral (AAV) vector to inject a fusion of citidine deaminase and dead CAS9 enzyme (dCAS9) to convert incorrect base pairs from C-G to T-A on the affected gene, phenylalanine hydroxylase (PAH). This demonstrated a significant drop in circulating blood levels of phenylalanine, as well as a correction of physiological signs of PKU. The research team is looking to conduct preclinical trials on other animal models, such as pigs. However, they state that follow-up studies will need to be done to determine whether any side effects or off-target mutations might occur with this new treatment, specifically stating to prevent mutations that lead to cancer.

And as the industry continues to experience a talent crunch, more partnerships between academia, research and suppliers have been happening in the industry. Most recently, client Pall Biotech announced a partnership with University College London; just one in a series of recent partnership announcements aimed at advancing innovation and ensuring proper access to resources and training for the next generation of bioprocess employees. More in Biopharm International here.

Elsewhere this week:

The FDA has launched guidance documents designed to help makers of generic ‘complex drugs.’

Complex drugs, as the name suggests, are hard to define. They are non-small molecule, non-biologic medicines composed of peptides, polymers, and natural substances formulated with liposomes, emulsions, suspensions, and polymeric materials.

The documents (here and here) cover drugs employing transdermal and topical delivery systems (TDS). Commissioner Scott Gottlieb said, “The increased transparency and predictability provided by these and other product-specific recommendations gives applicants seeking to develop generic copies of these complex products a better opportunity to efficiently advance these products and prepare better and more complete submissions.”

And keeping the momentum going (or at least the intention?) for a better-informed patient population and better drug pricing, President Donald Trump signed legislation banning ‘gag clauses’. These clauses currently prevent pharmacists from informing customers when it is cheaper to buy a drug without insurance.

The laws will mean some people will pay less at the pharmacy, but as STAT points out in their story, where does the enforcement come from here? And how many people will actually benefit in real life, since the explanation of how this will affect drug prices was vague.

In the animal health world…

The veterinary industry is experiencing a ‘paradigm shift’ in how pets are perceived by their families.  Dr. Craig A. Clifford, a medical oncologist and director of clinical studies at Hope Veterinary Specialists states that pets who lived 30 years ago were in the ‘Snoopy generation’- they ate and slept outside, generally not being part of the family. Today, pets are being considered an integral part of the family, with owners willing to pay more for veterinary services, even going as far as to insure their pets.

With the pet pharma industry growing at about 5% per year, larger drug companies have employed ‘spin-off’ animal health companies. For example, Pfizer created Zoetis, which gained independence from their parent company in 2013. Eli Lily’s previous company, Elanco, is slated for a promising growth and Merck joined in by rolling out Merck Animal Health.

In 2016, the pet pharma industry was valued at $6 billion, with a slated growth of 5% per year.