Deuterium Switching: An Obvious Way Around Patent Protection?
Some of the scientific advancements that splash across the headlines and color our imaginations also create huge revenues for the pharmaceutical industry. In 2021 alone, the United States health care system spent $603 billion on prescription drugs.[1] Most pharmaceutical drugs fall into one of two major categories; biologics or small molecules.[2] Biologics come from living cells, and are made by biological processes, these complex and large molecules are often hormones, vaccines, or antibodies. [3] Small molecules, on the other hand, are made by chemical processes, and they account for most of the patented drugs on the market, and around 90% of global sales.[4] On average, it costs over a billion dollars in research and development to successfully bring a pharmaceutical drug to market.[5] That’s why patent protection for pharmaceutical drugs is essential to protect companies’ investments and allow them to keep innovating.
Over the years, drug companies have been switching hydrogen atoms in small molecule drugs, for deuterium, a heavier isotope of hydrogen.[6] But simply replacing a 1H for a 2H, or changing it to a D in the chemical formula, is that a substantial change to the drug, or is that just patent infringement?
Courts have found that patent claims have enough wiggle room to cover these situations, under what’s called the doctrine of equivalents.[7] If an insubstantial change to an invention performs “substantially the same function in substantially the same way to obtain the same result,” that variation may be an equivalent to what’s covered by the patent claim.[8] And this doctrine of equivalents applies to mechanical or “chemical equivalents” in a composition.[9] Simply switching a hydrogen for deuterium may not be enough to get around the doctrine of equivalents.
But what if a “deuterium switch” conferred new qualities to the drug molecule? Deuterium-carbon bonds are stronger than hydrogen-carbon bonds, taking around ten times longer to break down.[10] A deuterium switch prolongs the drug’s lifespan within the body, the drug is harder to break down, which can improve efficacy without requiring a higher dosage or exposing patients to more side-effects.[11] And “new and useful improvement[s]” of existing inventions are patent eligible under 35 U.S.C. §101.[12]
Hundreds of patents have already been approved for deuterated versions of existing drugs, and these drugs are now starting to come to market.[13] In 2017, the Food and Drug Administration (FDA) approved the first deuterated drug for sale in the US, deutetrabenazine, a deuterated version of tetrabenazine, a 50-year-old drug.[14] In 2022, Teva Pharmaceuticals, the manufacturer of deutetrabenazine, brought in over $971 million in revenue from the drug, and that number is expected to grow in 2023.[15] The FDA has already announced that it considers deuterated-drugs to be different chemical entities from their non-deuterated relatives.[16] So should we expect to see a scramble for patents on deuterated versions of small molecule drugs?While improvements over existing inventions are patentable under §101[17], to obtain a patent, an inventor must show that the invention is not obvious at the time of filing.[18] If a person having ordinary skill in the art would have considered the improvement obvious, then the improvement is not eligible for a patent.[19] So how obvious would a deuterium-switch be for a skilled practitioner?
By analogy, stereochemistry was once in a similar situation.[20] The different enantiomers (mirror images, left and right-handed versions of compounds) held different benefits for drugs, and different enantiomers were able to get patents distinct from the racemic mixtures containing both enantiomers.[21] However, over time, the “chiral switch” became harder to patent, as the technique became more and more obvious.[22] What was initially a novel procedure, became obvious over time. While each different drug may be a unique situation, it seems clear that the obvious bar will continue to rise for deuterated drugs, and only time can tell how the patent landscape will change in the future.[23]
Footnotes
