Deuterated drugs; updates and obviousness analysis

ABSTRACT

Introduction: The pharmacokinetics and/or toxicity of many known drugs can be modified by selective deuteration, an area of significant commercial interest and scientific and regulatory progress.

Areas covered: This review firstly discusses recent developments in deuterated drugs including the FDA approval of deutetrabenazine. Secondly, it discusses 35 U.S.C. §103 ‘obviousness’ as it relates to recent patent prosecution, and also to Inter Partes Review (IPR). IPR is a new post-award review of patentability under §102 or §103, two IPR petitions upon deuterated drugs have been instituted and included §103 arguments. Finally, an extended analysis of §103 obviousness based upon the practices of major pharmaceutical companies is provided, that supports rather late priority dates, while §102 is also discussed.

Expert opinion: The total value of transactions involving deuterated drugs is close to $5 billion. While the importance of §103 ‘obviousness’ rejections remains in patent applications under current prosecution, IPR of issued patents is developing and will affect likely affect §103 interpretations in this area. However, patents are still issuing with later priority dates, and further litigation will likely occur.

KEYWORDS:

• Deuteration
• inter partes review
• obviousness
• patent

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Corrigendum

Article Highlights

• Deuteration of a known drug, the ‘deuterium switch’, can greatly improve pharmacokinetics or toxicities by modifying metabolism.

• The first deuterium switch drug (deutetrabenazine) was approved by FDA in 2017, for Teva (which acquired the program with Auspex for $3.5 billion). Vertex also acquired intellectual property on deuterated ivacaftor from Concert Pharmaceuticals

• §103 ‘obviousness’ continues to be of major importance in patent prosecutions and now also post-award Inter Partes review. This is likely to play a significant role in the final litigation and disposition of §103 ‘obviousness’ in this area, and an analysis of obviousness performed here using the actual patenting practices of over 30 major pharmaceutical companies.

This box summarizes key points contained in the article.

Declaration of interest

G Timmins is Chief Science Officer and co-founder of SpinCeutica, a company developing 13C labeled isoniazid for drug resistant tuberculosis. He is also co-founder and adviser of Avisa Pharma, developing 13C based stable isotope breath tests for the diagnosis of lung infection. Through the tech transfer arm of UNM (STC.UNM) Dr Timmins holds several patent in stable isotope drugs and diagnostics. The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper was funded by the U.S. Department of Health and Human Services National Institutes of Health National Institute of Allergy and Infectious Diseases grants AI117224 and AI122313.