Last Monday, the U.S. District Court for the District of New Jersey invalidated Bayer's (BAY) U.S. Patent No. 6,787,531 on grounds of obviousness, relying heavily on KSR. The '531 patent, claiming pharmaceutical formulations of micronized drospirenone and ethinylestradiol, protects Bayer's Yasmin birth control pill. Barr Labs (BRL) had challenged the '531 patent in a paragraph IV certification with its ANDA filing.
The court's opinion (pdf file) follows a bench trial held over a two-week period late last year. The main issues in the case were whether it would have been obvious
to (1) micronize drospirenone so as to increase its bioavailability, and (2) not protect the drospirenone from the gastric environment with an enteric coating.Drospirenone is a relatively difficult molecule to formulate due to its poor water solubility and sensitivity to acid.
While Bayer argued that the prior art taught away from micronizing acid-sensitive drugs like drospirenone, the court concluded:
"Undoubtably, there would be some concern about dissolution of a poorly water soluble acid sensitive drug, but the person of ordinary skill in the art could conclude that micronization is a viable option." Similarly, while Bayer asserted that the prior art taught that acid sensitive drugs must be enteric coated, the court credited Barr's argument, finding that "inter- and intra-subject variability is a major disadvantage" of enteric coating, and concluding therefore that one "could not rule out formulating a micronized drospirenone without enteric coating." Furthermore, the court concluded that a prior art reference teaching that drospirenone isomerzies when exposed to hydrochloric acid in vitro (Nickisch) should be discounted because its results were not corroborated by in vivo studies.
In addition to concluding that the invention claimed in the '531 patent would have been obvious, the court concluded that the invention was obvious to try:
As noted, in KSR the Supreme Court ruled that a patent claim may be obvious if the combination of elements was "obvious to try." In this case, the testimony was limited to discussion about whether or not to employ to common formulation techniques -- micronization and enteric coating. As in KSR "there are a finite number of identified predictable solutions." In this case, based on the prior art as a whole, micronizing and immediately releasing drospirenone was obvious to try.
The '531 patent, which would expire in 2020, is one of three Orange Book-listed patents for Yasmin. The others are U.S. Patent No. 5,569,652, claiming methods of use and expiring in 2013; and U.S. Patent No. 6,933,395, claiming compositions and expiring in 2017. Although Barr is the first ANDA filer for a generic version of Yasmin, if Barr filed paragraph III certifications with respect to the '652 and '395 patents, then it must wait at least until those patents expire before it launches its generic product.
The U.S. market for Yasmin is approximately $500 million annually. Bayer is expected to appeal last Monday's decision to the U.S. Court of Appeals for the Federal Circuit.