Treating the Untreatable: Harnessing Biological Processes to Fight Disease
Biologics – complex medicines made by living cells – can have significant therapeutic benefits over chemically produced small molecule drugs in treating severe illnesses. These complex compounds, which can take many years to develop, are isolated from a variety of cellular sources using cutting-edge biotechnologies and include therapeutic proteins (such as insulin and growth hormone) and monoclonal antibodies.
Why are biologics so important?
Because of their larger and more complex molecular structure, biologics can provide precise and personalized treatments with potentially fewer side effects and safety concerns. They are often used to treat severe and life-threatening diseases and may also be used to manage a range of medical conditions for which no other treatments are available.
Recent research shows that biologic therapies have changed the face of oncology by targeting cancerous cells while reducing the effect on normal tissue. A 2019 study on asthma found that all five of the approved biologics for severe asthma reduced asthma exacerbations rates by half and also improved lung function and quality of life. In clinical trials for migraine biologics, headaches were reduced by as much as 50% in patients experiencing multiple migraine days each month.
What is Teva doing in this space?
Working in the areas of cancer, migraine, respiratory conditions and inflammatory bowel disease (IBD), Teva is focused on identifying highly targeted antibodies to fight disease. With 11 innovative medicine launches, 16 products in development and 231 in the portfolio, Teva has acquired industry-leading experience in screening and selecting disease-fighting antibodies for effective therapies.
The process starts at Teva’s Discovery center in Sydney, Australia, with work also taking place at innovative R&D centers in Netanya, Israel, Debrecen, Hungary and West Chester, Pennsylvania. Here a biologics manufacturing facility also produces clinical batches.
A new $500 million large scale, end-to-end biologics facility in Ulm, Germany, was recently opened to provide more controlled and flexible manufacturing capabilities, improving speed and responsiveness, reducing costs and ensuring the quality and consistency of supply.
The science: how do monoclonal antibodies work?
Antibodies are proteins that are naturally produced against things that the body perceives as foreign, such as infectious agents and some cancer’s cells. Scientists can exploit antibody-producing mechanisms to identify highly selective antibodies to neutralize disease-causing proteins.
Think of it like this. The cancer cell has a receptor, like a lock. The monoclonal antibody is the key that fits into that lock. The binding process is very specific, there is only one key for a particular lock. And when the two bind, when the key fits into the lock, it transforms the way that disease molecule works. It either stops functioning or changes to a different way of functioning, depending on what’s required.
How are monoclonal antibodies created?
The creation process exploits the immune system’s antibody producing cells, called B-cells, which are screened to discover those producing antibodies which will work against the disease.The process involves screening huge numbers of cells to find one that works – it’s like looking for a needle in a haystack.
Scientific advances: new technology is speeding up the process
A new approach called single B cell technology massively increases the number of B cells that can be assessed for the antibodies that they produce. By using next generation single B cell technology, millions of antibodies can be screened to effectively find that needle in the haystack.
Teva has been at the leading edge of this change. Using nanoscale culture and screening, researchers can screen 1,000,000 B cells at one time by putting them individually into tiny culture vessels. Each single cell is individually analyzed to determine if it is producing desirable antibodies – if so, that B cell can be isolated and its antibody can be reproduced.
Analyzing many more B cells – much faster – has increased the probability of success, explains Anthony Doyle, Vice President of R&D and Head of the Biologics Discovery site in Sydney.
“We have been early adopters, at the cutting edge of the single B cell technologies as they have arisen in recent years” Anthony says. “That accumulated knowledge – and our experience working with multiple generations of single B cell technologies – gives us a real advantage in finding and developing new antibodies that not only work, but that also can be manufactured effectively. We have the tools to advance new treatments for some diseases that other companies haven’t been able to develop.”
Meet the team
“There are two important elements in nanoscale culture and screening,” explains scientist James Halstead, who leads the Cell Line Development team in Sydney. “One is a high throughput imaging microscope that can image thousands and thousands of cells incredibly quickly. The second is microfluidics. Fluidics is like the central heating in our houses that pumps water through the house and microfluidics is the same, but on a nano scale, working with very small channels and very small amounts of fluid. If you use the microfluidics in a particular way, you can move single cells in a very controlled way. And that's important, because it allows us to separate single cells, and then use the high throughput imaging to image thousands of them and find the best ones to produce our antibodies.”
The technology has allowed the team to work faster and more efficiently, says James. “We can run more experiments than ever and that allows us to learn more and make better decisions. We can also achieve more sensitive measurements. And the more you can measure your experimental system, in our case cells that are making an antibody, then the better you can engineer them, the better you can test them, and the better you can predict what's going to work and what's not.”
Teva is focused on disease targets, striving to find monoclonal antibody solutions that other companies haven’t identified, working with unmet medical needs to help patients whose requirements are not being answered.
Teva is also working with some of the top scientific minds in the business to develop new innovative lines. “What never changes is the necessity for thinking,” says James. “The new technologies are incredibly powerful but are only as good as the scientists who use them. I’m lucky enough to supervise a big team of bright young talented scientists who help make these antibodies. But that’s just part of our job. The other part is discovering new technologies and keeping up to date with developments in the field.”
Senior Research Assistant Jacinta Watts is part of that team, working on everything from molecular cloning to single cell cloning and tissue culture.
Her colleague, Research Scientist Vitri Dewi, says she loves seeing the work they do at the laboratory bench going through drug and manufacturing development pipelines.
“Biologics development has opened the door to new and exciting ways to manage diseases that haven’t had effective treatments in the past,” says Anthony. “That means more patients will be able to get the help they need to improve their health – and their lives. The exciting thing is that Teva is in a strong position to make a major contribution.”
Find out more
- Go behind the scenes at Teva Israel with Biologics VP Nir Shapir to explore the processes involved in creating biosimilar medicines
- Discover how innovation and technology is redefining the pharma industry
- Join our teams supporting patients across the globe – browse our career opportunities