“Computerized Methods Bypass Patent-Protected Drug Syntheses: A New Approach in Pharmaceutical Industry”

In a groundbreaking development, researchers from Poland and South Korea have developed a computerized method that can suggest synthetic strategies for essential drugs while bypassing patent-protected aspects. This innovative approach, which could potentially revolutionize the pharmaceutical industry, was published in the journal Chem on January 17.

Pharmaceutical compounds and life-saving medications are among the most closely guarded trade secrets in the global industry. The researchers have built on recent work that programmed computers to identify synthetic pathways leading to complex pharmaceutical molecules. The new method suggests only synthetic strategies that avoid patent-protected aspects of essential drugs.

“When we started this project, I was somewhat skeptical that the machine would find any viable synthetic alternatives—after all, these are blockbuster drugs worth gazillions of dollars, and I was sure that the respective companies had covered the patent space so densely that no loopholes remained,” says senior author Bartosz Grzybowski, a professor of chemistry at the Ulsan National Institute of Science and Technology (South Korea) and the Polish Academy of Sciences. “It turns out that the loopholes are there, and we can find new retrosynthetic pathways that circumvent the patents entirely.”

Pharmaceutical patents protect a company’s intellectual property and prevent competitor companies from using certain key synthetic solutions. These solutions are developed painstakingly by experiment to maximize yield, increase purity, and reduce costs when attempting to produce desired compounds.

The researchers “froze” challenging portions of each target molecule, forcing the computer to substitute unconventional yet chemically plausible approaches based on mechanistic rules. They tested their system on three notable commercial medicines with different chemical hurdles: linezolid, a last-resort antibiotic; sitagliptin, an antidiabetic drug; and panobinostat, a multiple myeloma treatment.

In each case, when allowed to run without constraints, the program recommended the commercial syntheses. But when even a few atoms and bonds were designated as untouchable, it innovated by applying Chematica’s existing functions to propose new plans that neatly avoided those already patented.

“By algorithmically locating the key bonds on which patents hinge and propagating them down Chematica’s retrosynthetic trees, we can generate synthetic solutions from alternative yet economical starting materials, achieving a real practical impact,” Grzybowski says.

Chematica’s patent-dodging abilities could also alter how chemists approach intellectual property and patent law. For example, machine-aided searches could be used to restrict many different parts of a target molecule, lumping radically different syntheses into a single airtight patent.

However, Grzybowski notes that such a patent would not necessarily stay loophole-free forever, thanks to the likely future experimental discovery of novel reactions driving chemical knowledge forward through healthy competition.

The researchers hope that their software will aid pharmaceutical companies in better protecting their intellectual property and, simultaneously, will help accelerate research and development in organic chemistry by supplying synthetic routes that differ from standard approaches.

“This work illustrates the benefits of pushing chemists to think algorithmically and asking computer scientists to grasp key chemical concepts, delivering chemical artificial intelligence results that matter beyond the confines of academia,” adds co-author Piotr Dittwald, a research fellow with training in mathematics and computer science.