How to Make Drugs – Without Patents Getting in Your Way

Some of the most closely guarded secrets in the world are also some of the most important. The formulas and synthesis methods for a variety of crucial medications are patented due to the billions of dollars companies make off of them. As prices of prescription medications skyrocket, stories abound of pill-cutting and other tactics to cope with inability to afford needed medication, and many people are forced to go without entirely. The average American spends over $1,000 on prescription drugs per year, and, while insurance can soften the blow, many are left paying hundreds or thousands of dollars out of their pocket.[1]For people without insurance or with medical conditions that require expensive treatments, the situation is even more dire.

Any option to give wider access to affordable care is a good one. New organic synthesis software, called Chematica, may hold the key. This software uses retrosynthesis, the practice of retracing steps needed to create a chemical, to unlock new ways to synthesize life-saving drugs in a way that is both legal, without interfering with current patents, and chemically plausible, based on existing mechanisms.[2]

The research team, composed of professors in Poland and South Korea and including the lead developer of the software, attempting to find these alternate pathways tested Chematica on three different medications.[2]The first, linezolid, is an antibiotic used as a last resort when others prove ineffective.Sitagliptin is a medication for diabetes that can increase the production of insulin and regulate blood glucose. Finally, panobinostat is a drug used to kill malignant cells in multiple myeloma, a form of blood cancer.[3]It is also a promising treatment for other kinds of cancer. Alternate synthesis methods for these drugs would have a significant impact for patients, and the molecules gave Chematica a variety of challenges to test its ability to come up with alternatives.[4]

Chematica uses artificial intelligence to conduct retrosynthetic analysis. This is a technique in which the structure of the target molecule is given, and the steps to produce it are then traced back to starting molecules that are much simpler and more readily available.[4] At first, when given the three drugs, the software, as could be predicted, gave the standard, patented methods of synthesis. This reinforced the fear that pharmaceutical companies truly do have intellectual property rights over the manufacturing of these medications.[2]However, when the bonds that produced the most challenges were locked, meaning that the pieces of the molecule that were most relevant to the patent were designated as not being formed through the patented method, something amazing happened.[5]Chematica was able to work around the blocked steps to create entirely new ways of producing linezolid, sitagliptin, and panobinostat[4]. These syntheses followed reactions that were already recognized as chemically plausible without running the risk of violating a patent.

As all three molecules presented different structures and challenges, the ability to work around key steps to create all of them is promising for producing the drugs without the companies holding the patents.[6]If all three of these molecules have viable alternate pathways, the same would likely be true for drugs similar to any of the three or that present the same structural challenge, which would broaden the effect of these findings.[2]Upon testing in the lab, if the steps suggested by Chematica do function as suggested, other companies may be able to also sell the drugs or some with similar structures and function. Introducing competition and alternatives into the prescription drug market would likely have the effect of lowering prices, which would increase patients’ access to drugs they desperately need.

However, hope about the increased access may be premature, as the alternate syntheses await testing. While the steps used do follow what we already know works in similar reactions, and the starting materials given are relatively inexpensive, sometimes a synthesis that works in theory still goes wrong in the lab. Also, now that these findings are public, there are worries that companies will just patent the new methods, owning  all reasonable approaches to making the drug.[3]In that case, introducing competition into the market will be even more necessary and difficult, and the current crisis with prices for prescription drugs will not be resolved.

The potential for alternatives to expensive life-saving drugs through Chematica holds significant promise, but is it too good to be true? We have yet to find out.

References:

  1. Kamal, R., Cox, C., & McDermott, D. (2018, December 10). What are the recent and forecasted trends in prescription drug spending? Retrieved February 10, 2019, from https://www.healthsystemtracker.org/chart-collection/recent-forecasted-trends-prescription-drug-spending/#item-nominal-and-inflation-adjusted-increase-in-rx-spending_2017
  2. Farooq, I. (2019, January 18). Computer program that could bypass patents to produce synthetic drugs. Retrieved February 10, 2019, from https://www.europeanpharmaceuticalreview.com/news/83106/intellectual-property-patent/
  3. Welter, K. (2019, January 21). Patent-busting AI tool navigates around protected drug pathways. Retrieved February 10, 2019, from https://www.chemistryworld.com/news/patent-busting-ai-tool-navigates-around-protected-drug-pathways/3010015.article
  4. Molga, K., Dittwald, P., & Grzybowski, B. A. (2019, January 17). Navigating around Patented Routes by Preserving Specific Motifs along Computer-Planned Retrosynthetic Pathways. Retrieved February 10, 2019, from https://www.sciencedirect.com/science/article/pii/S2451929418305679?via=ihub
  5. This computer program makes pharma patents airtight. (2019, January 17). Retrieved February 10, 2019, from https://www.sciencedaily.com/releases/2019/01/190117110805.htm
  6. OECD. (2014, June 03). Intellectual property issues and synthetic biology. Retrieved February 10, 2019, from https://www.oecd-ilibrary.org/science-and-technology/emerging-policy-issues-in-synthetic-biology/intellectual-property-issues-and-synthetic-biology_9789264208421-8-en;jsessionid=gdCMOkLGkyiRE_kXeKd9d2N-.ip-10-240-5-93