MONOCLONAL ANTIBODIES

The patent system is particularly effective in promoting innovation in the pharmaceutical sector. Throughout its history, it has encouraged the invention of new drugs that have contributed to the improvements in living standards and longevity that have been experienced in recent decades.

The invention that is the subject of this entry is an example of a revolutionary invention in the pharmaceutical sector, although, as we will see, it was not initially patented. It is monoclonal antibodies, which are currently used to fight numerous diseases.

Although it is increasingly difficult to attribute the paternity of an invention to one inventor or a small number of inventors, given the complexity of laboratory research, which often involves numerous scientists, on this occasion, there is a consensus that the invention can be attributed to scientists César Milstein (Argentina) and George Köhler (Germany), both of whom worked at the Cambridge Molecular Biology Laboratory. In 1975, they developed the hybridoma technique, which makes it possible to produce large quantities of identical antibodies or “monoclonal antibodies”. Laboratory mice are exposed to the antigens against which the antibodies are to act. B cells or B lymphocytes are generated and fuse with myeloma cancer cells. The resulting cells that generate the desired antibodies are cloned, multiplied in culture in large numbers, hence the name monoclonal antibodies. Due to the involvement of mice in the production, they were called chimeric antibodies. It is now possible to obtain fully human products, thus reducing the chances of rejection by the patient’s immune system.

César Milstein and George Köhler won the Nobel Prize for medicine in 1984 for their invention, which can be considered one of the most important inventions in the field of biotechnology in recent decades. Surprisingly, however, it was never patented. The British Medical Research Council alerted the National Research Development Corporation (NRDC), the public body responsible for filing patent applications for research carried out in public institutions, but the NRDC decided not to file a patent and the paper on the process of obtaining monoclonal antibodies was published in Nature. This lack of a patent had political repercussions. In 1980, British Prime Minister Margaret Thatcher (who had a degree in chemistry) visited Cambridge University and had to listen to two stories about two catastrophic cases where research results had not been patented, forgoing substantial revenues. One was an image intensifier developed by the Radio Astronomy Observatory MRAO and the other the invention related to monoclonal antibodies in the molecular biology laboratory. It seems that the news caused her serious anger and probably influenced the demise of the NRDC, which merged with the National Enterprise Board in 1981 to form the British Technology Group, a new body charged with managing the transfer of technology generated by British public research. In any case, it is claimed that Milstein did not regret the lack of a patent, as it supposedly gave him more freedom to pursue research.

One wonders what would have happened if this invention had been patented. Perhaps the UK’s coffers would have been flush with revenue, but would technological progress in the development of such medicines have been delayed? Some practitioners argue that patents on highly disruptive innovations have had this effect in the past in aeronautics or 3D printing and perhaps gene editing.

The first patent GB2039948B on technology for obtaining monoclonal antibodies was published in 1980, based on a British priority.

This first patent protects a method for obtaining monoclonal antibodies against tumour antigens.

The first monoclonal antibody to be authorised was Rituximab, in 1997, against cancer, specifically non-Hodgkin’s lymphoma. It is also used for rheumatoid arthritis. The great success of monoclonal antibodies has been in the treatment of inflammatory autoimmune diseases such as rheumatoid arthritis, psoriasis and inflammatory bowel diseases. Monoclonal antibodies have also been developed to combat infectious diseases.

Estructura del Adalimumab. Fuente: Wikipedia

In recent years, research has focused on the development of more stable, safe, effective and specific monoclonal antibodies. A list of the different monoclonal antibodies currently available can be found here. Some of these products have become major successes, such as Adalimumab, trade mark Humira, an anti-TNF (tumour necrosis factor inhibitor), which has helped millions of patients with autoimmune diseases to go into remission. It has also been a major commercial success for the innovator Abbvie. Although the prices of these drugs are very high, and the patent life is extended using various techniques, biosimilars are already being marketed, which has allowed a reduction in the price of Adalimumab.

Unlike other pharmaceuticals, these biological medicines are not referred to as generics, but rather as biosimilars. Generic medicines are molecules obtained synthetically and through chemical reactions identical to the original ones. In the case of biological products, the structure is very complex and it is not possible to obtain “identical” drugs but biosimilars, i.e. biological products that have demonstrated similar performance in terms of quality, efficacy and safety. Obtaining biosimilar products is much more complex than obtaining “generics”. It requires more time and investment.

It has undoubtedly been a great invention that has contributed to increasing the quality of life and longevity of millions of people affected by various types of diseases.

Leopoldo Belda Soriano

En español

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