A patent is not a dogma

How a computer cheats the patent system of "Big Pharma"

Alexey Aleksenko, Forbes, 22.01.2019

An algorithm has been developed that allows finding ways to synthesize pharmacological drugs bypassing patent restrictions. The same program will help formulate patent applications so as to make them invulnerable

In modern pharmacology, intellectual property is the most important asset, and its protection is a separate industry where a lot of know—how has been accumulated. When starting work on the Chematica project, researchers from Poland led by Bartosz Grzybowski, who is currently working in South Korea, did not expect that the computer algorithm they developed (Molga et al., Navigating around Patented Routes by Preserving Specific Motifs along Computer-Planned Retrosynthetic Pathways) would be able to revolutionize this area of knowledge. Nevertheless, they seem to have succeeded: the program easily finds strategies for the synthesis of complex chemical compounds that circumvent the restrictions imposed by the relevant patents. "It turned out that there are still a lot of loopholes," says Grzybowski. "We were able to find new retrosynthetic pathways that completely bypass patents."

Pharmacological patents protect intellectual property by preventing competitors from using key technological solutions. These solutions are designed to optimize the output of the target connection, ensure maximum purity and reduce production costs. A patent is usually formulated in such a way as to exclude workarounds that, even if less effective, could still attract competitors by eliminating the need for them to acquire a patent.

However, Polish researchers tried to look for such ways. They "froze" the key elements of the chemical compound, prompting the program to offer, albeit less effective, but still possible from the point of view of chemistry, workarounds. The program was tested on three commercial drugs. Linezolid is an antibiotic from the group of oxazolidinones — the so-called antibiotic of last resort, used against resistant infections. Sitagliptin is prescribed for diabetes, and panobinostat is an antitumor therapy drug.

In each of the three cases when a computer program was allowed to choose the synthesis path at its own discretion, it offered exactly the technology that was patented by the manufacturer. But then the authors of the algorithm fixed some atoms and chemical bonds, declaring them "untouchable". In this case, the program found an alternative way to assemble the required molecule from other components. It turned out that in all three cases considered, even when the algorithm was forbidden to touch all parts of the molecule protected by the patent, it was able to offer practically feasible chemical solutions based on alternative starting materials — sometimes unexpected, but quite acceptable from an economic and technological point of view.

The Chematika algorithm can seriously affect the practice of patent work: a machine search for alternative options will allow you to formulate a patent application in such a way as to completely eliminate the possibility of circumvention, thereby making the patent invulnerable to competitors.

Bartosz Grzybowski nevertheless notes that this invulnerability is not absolute: the development of chemistry may lead to the fact that synthesis paths will be proposed, which today the program considers unacceptable. Thus, the described algorithm does not limit healthy technological competition driving progress in the field of pharmacology. Moreover, Polish scientists believe that their program, by closing obvious workarounds, can push chemists to more actively search for new opportunities and approaches to organic synthesis. Another participant in the study, mathematician Peter Dittwald, draws attention to how the cooperation of chemists and programmers brings the creation of "chemical artificial intelligence", which can be used not only in academic research, but also in industry.

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