How Companies Can Speed Deals With Universities

I recently closed a deal with a company. Nothing huge and exciting, but a "deal" nonetheless. What should have been a happy occasion was marred a little when I found out the other party was making back-channel complaints about the length of time it took to close the deal.

Of course, complaints about the "slowness" of university technology commercialization offices (TCOs) are nothing new. I've blogged about the issue before in this space, but it is such a recurring theme that it probably deserves some more attention.

I was a little surprised to get complaints in the particular case because it was a deal that was fated to take forever because (a) the technology being licensed was not the most exciting technology that the university owns, (b) the company was licensing it primarily for strategic purposes and wasn't planning to make it the focus of their research and (c) not much money was changing hands. Deals like are just going to take forever and result in duels to the death over legal minute because neither party is hugely incentivized to close.

Prominently among them are monoclonal antibodies. These are antibodies that can be produced by cells which can be derived from a single unique parent cell. In the 20^th century Paul Erlich postulated that if a compound could be made to target a disease causing organism, then it could be used as a magic “bullet” to specifically target that organism. This would be especially useful in treating diseases such as cancer, which was until recently still widely tackled by the use of chemotherapy, which resulted in hair loss and much suffering to the patient, as non cancer cells were also being destroyed. A typical way of producing monoclonal antibodies is the fusing of myeloma cells with mouse or rabbit cells that have been immunized with a particular antigen, to cause the resultant hybridoma cells to produce the required antibody.

For mass production, the gene for a particular antibody can be inserted into a genome of a particular cell. For industrial purposes, the Chinese Hamster Ovary (CHO) cell is still the cell line of choice for production of monoclonal antibodies. A selective marker is included in the cell’s genome, and under the selection of components in the culture media, the cells not only multiply but also secrete the required antibody. Not only is it convenient that the cells perform the work for us, it is also vital that they do so. The structure of Lipitor (below) may be synthesizable in a laboratory, but to artificially create the complex structure of a monoclonal antibody, which is actually a fully folded protein, is as yet inconceivable on the large scale.

Lipitor (left), is a single molecule that is chemically synthesized, unlike the complex protein structure of a monoclonal antibody (right).  Recombinant DNA technology and cell culture make it possible to mass produce it. Photo Source: http://www.thechemblog.com

Since ReoPro was approved for the treatment of cardiovascular disease in 1984, nearly two dozen monoclonal antibodies have been used in the treatment of cancer related ailments, accounting for large sales annually.  Avastin, originally of Genentech and now Roche, was its biggest seller in 2009, with figures reaching nearly 6 billion dollars.  Together with Lucentis, and Herceptin and Nutropin in the near future, the drug is currently to be produced in their multi million dollar complex in Tuas, Singapore, the newest addition to its conglomerate.

Aside from monoclonal antibodies, viral vaccines also come under the classification of biologics.  Already in the 18th century, Edward Jenner’s method of treatment to tackle the smallpox disease paved the way for viral vaccine production.  Today, vaccines are produced in several ways.  The virus can be typically grown in medium such as tissue culture, eggs, and even mouse brain cells.  The virus is then inactivated so that its replicative function is destroyed, producing a viral vaccine which will then stimulate an immune response in the patient without causing the disease.  In addition to its antibiotics facility in Singapore, GlaxoSmithKline began an investment in a viral vaccine production plant in Tuas Biomedical Park, Singapore that will focus on the bulk production of two bulk paediatric vaccines for preventing infectious disease such as meningitis and typhoid.

Structure of Haemophilia A Factor VIII, used for treatment of patients with the blood clotting deficiency. Photo Source: http://www.nwabr.org/studentbiotech/winners/studentwork/2007/WB_BA_TRONGTHAM/5_structure.htm  

Yet another example of a biologic product that will soon be made in Singapore is haemophilia factor VIII.  Haemophilia A, which is a deficiency of clotting factor VIII, occurs in about 1 in 5000 - 10000 male births.  The patients are never fully cured of haemophilia since it is a hereditary disorder, and are thus unable to efficiently control blood clotting or coagulation.  Factor VIII was once obtained through patients via donated blood plasma, and posed a risk of contaminated blood samples being unknowingly sent to the patient.  Recombinant protein synthesis, as with the case of monoclonal antibodies, have now removed this risk of obtaining tainted blood from donors.  The production of factor VIII will be one of Baxter Biosciences projects in Woodlands Industrial Park, Singapore.

While biologics is already a billion dollar business, there are as yet still a lot of new drugs and improvements to be made.  Research and development in biologics is currently carried out worldwide, as well as in Singapore at the Bioprocessing Technology Institute, A*STAR research institute, Biopolis Singapore.   As a lot of biologics are produced via cell cultures, there is still much to be discovered in getting cells to produce more products, and improving the efficiency of purifying those products from the culture to convert them into injectable or ingestable medicines.  In future, cell therapy and even stem cells will be a bigger part of biological therapeutic drug products and innovation pipeline. Forays into these still largely uncharted territories promise to yield new and interesting findings.

This article is contributed by Raymond Chia. Raymond has previously worked in A*Star Bioprocessing Technology Institute and is currently a biotechnologist at Roche Technical Operations in Singapore.