Deuterated drugs: where are we now?
Deuterated drugs: where are we now?
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DOI：
10.1517/13543776.2014.943184
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发表时间：
2014-10
影响因子：
6.6
通讯作者：
Timmins GS
中科院分区：
文献类型：
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作者：
Timmins GS
现有药物的氘代版本可以表现出改善的药代动力学或毒理学性质，因为更强的氘-碳键改变了它们的代谢。人们对这一方法的发展现状很感兴趣。本综述涵盖了最近在这一领域的美国专利申请和起诉，这些申请和起诉是基于对现有药物的氘代版本的代谢的有益修改。35 USC的当前状态§103“显而易见”的拒绝，强调的是战略的发展，以克服这种拒绝。目前的试验和市场考虑也进行了讨论。氘代药物加起来至少价值10亿美元。在这一领域，明显性拒绝的可能性似乎正在增加。然而，对来自氘化的代谢结果的仔细阐明使得能够允许，所述代谢结果从现有技术中是无法预期的，而是出乎意料的和不明显的。显示药物氘化通过目前不属于现有技术的机制改变药代动力学，氘化药物也是成功的。这些和其他战略的发展，加上发展广泛的专利基础，将使该领域在一段时间内保持商业吸引力。
Deuterated versions of existing drugs can exhibit improved pharmacokinetic or toxicological properties due the stronger deuterium-carbon bond modifying their metabolism. There is great interest in the current state of development of this approach. This review covers recent US patent applications and prosecutions in this area, that are based upon beneficial modifications in metabolism of deuterated versions of existing drugs. The current state of 35 U.S.C. §103 ‘obviousness’ rejections, are emphasized as is the development of strategies to overcome such rejections. Current trials and market considerations are also discussed. Deuterated drugs collectively are worth at least a billion dollars. It would seem that the likelihood of obviousness rejections is increasing in this area. However, careful elucidation of metabolic outcomes from deuteration that would not be anticipated from the prior art, and are instead unexpected and unobvious, has enabled allowance. Showing drug deuteration alters pharmacokinetics by mechanisms not currently part of the prior art surrounding, deuterated drugs has also been successful. Development of these and other strategies, combined with developing the extensive base of issued patents will enable the field to remain commercially attractive for some time.