scyther5 /
16 July 2018Americas

Federal Circuit sides with Bayer and Endo in testosterone case

The US Court of Appeals for the Federal Circuit confirmed the validity of two patents covering a testosterone replacement therapy on Friday, July 13, in a win for Bayer Pharma and Endo Pharmaceuticals Solutions.

Bayer owns two US patents (numbers 7,718,640 and 8,338,395) for Aveed (testosterone undecanoate), a long-acting injectable testosterone replacement therapy. The priority date for the patents is 2003.

Drug maker Endo owns the approved New Drug Application for Aveed.

Aveed needs to be administrated five times a year after the initial two injections, a rate which is much less frequently than previous therapies required. It also prevents fluctuations in testosterone levels, an issue which was associated with other injectable testosterone therapies.

In 2014, the predecessor to Custopharm, a generic injectable developer, submitted an Abbreviated New Drug Application (ANDA) to the US Food and Drug Administration to market a generic version of Aveed.

Bayer and Endo then filed a patent infringement lawsuit against Custopharm at the US District Court for the District of Delaware, and in response, Custopharm argued that the two patents covering Aveed should be invalidated.

Custopharm referred to three scientific articles, published before 2003, which describe small clinical studies relating to injectable therapies. The articles inherently disclose benzyl benzoate and castor oil as co-solvents, Custopharm claimed, thereby rendering Bayer’s patents obvious.

Each vial of Aveed contains testosterone undecanoate solution in a mixture of benzyl benzoate and castor oil, which act as co-solvents.

In 2016, the Delaware court held that Custopharm had failed to demonstrate that the patents were invalid as obvious.

The court said that the prior art did not disclose the injection dosage and that Custopharm did not show that a person skilled in the art would have been motivated to lower the dosage found in the articles to the one disclosed in the Aveed patents.

Also, the articles did not disclose the injection schedule and did not disclose benzyl benzoate as a co-solvent, the court said. Inherency only arises if it is the “natural result” of the prior art, and Custopharm failed to prove this to be the case here.

On appeal, Custopharm argued that those skilled in the art would have realised that patients were being overdosed and would have reduced it accordingly.

The appeals court agreed with the Delaware court. It said that Custopharm must show clear and convincing evidence to justify a finding of obviousness, and not just that prior art does not preclude lowering the dose.

“Custopharm’s overdose theory improperly assumes that the only solution to overdosed patients is to reduce dosage rather than extending the injection intervals,” the court said.

The court added that even if a person skilled in the art realised that a co-solvent was necessary, there were others available, ie, the use of benzyl benzoate would not have been the only option.

The articles relied on by Custopharm failed to disclose the co-solvent formulation or the ratio of benzyl benzoate to castor oil, the court concluded.

It affirmed the district court’s decision and dismissed the appeal.

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