On Feb. 10, 2022, Federal Circuit affirmed District Court’s decision and found patents invalid as obvious.

 

Adapt pharma / Opiant pharma (Plaintiffs) owns NDA for Narcan® (Naloxone, 4mg) Nasal Spray which was approved by USFDA on Nov. 18, 2015. Narcan is a branded nasal spray used to treat patients suffering from an opioid overdose. Teva (Defendant) filed ANDA with P-IV certification to market generic version of the drug. Plaintiffs sued Teva for infringement of patents, US 9,468,747 US 9,561,177, US 9,629,965 and US 9,775,838. Teva stipulated to infringement but asserted that patents-in-suit are invalid under obviousness. The Court held a two-week bench trial and concluded that the patents are invalid under obviousness. You can read the detailed summary “here” on this blog.

 

Adapt challenged district court’s finding on mainly 3 points: (1) its finding that a skilled artisan would have been motivated to combine the prior art references to arrive at the claimed invention; (2) its finding that the prior art, as a whole, does not teach away from the claimed invention; and (3) its findings related to Adapt’s proffered objective indicia of nonobviousness.

 

Federal Circuit with respect to first point said that district court’s finding was supported by ample evidence in the record—provided a detailed explanation as to why a skilled artisan would have been motivated to combine the prior art references to arrive at the claimed invention. First, the district court found that a skilled artisan would have been motivated to improve on the MAD Kit because its shortcomings were well-known. Because,  FDA in 2012 discussed its interest in improving the MAD Kit (used to administer injection formulation through nasal device). Second, the district court found that a skilled artisan would have been motivated to use sodium chloride, hydrochloric acid, BZK, and EDTA in an intranasal naloxone formulation. There were sufficient disclosures in the prior arts to support this. Third, the district court found that a skilled artisan would have been motivated to use the claimed 4 mg dose of intranasal naloxone. At the 2012 meeting, “the FDA specifically mentioned that it was curious about the bioavailability of an intranasal naloxone product as compared to the existing intravenous or intramuscular products.” The district court found that prior art (Strang) estimated that “an intranasal dose of 3mg to 4mg would be bioequivalent to the FDA-approved 1mg injectable dose.” Thus, district court correctly found that a skilled artisan would have been motivated to combine the prior art references to arrive at the claimed invention.

 

Federal Circuit with respect to second point said that prior art (Wyse), as a whole, did not teach away from the claimed invention. Adapt argued that the Wyse reference taught away from using BZK as a preservative. But Court said that the concentration disclosed in Wyse is 8.5 times greater than the concentration of BZK claimed in the patents-in-suit. The skilled artisan reading Wyse would not have been dissuaded from using BZK at all in an  intranasal naloxone formulation, only from using such high concentrations. Moreover, other references (Davies
and Kerr) taught the use of BZK specifically in intranasal naloxone formulations at concentrations similar to the claimed concentration, and that the prior art did not express “any concerns” with the stability of these formulations.

 

Federal Circuit with respect to third point said that although the district court’s analysis of the objective indicia in the opinion follows its discussion of the prima facie case of obviousness, there is nothing inherently wrong with that.  Moreover, the district court’s analysis was “part of the whole obviousness analysis, not just an afterthought” to a forgone legal conclusion [Leo Pharm. Prods., Ltd. v. Rea, 726 F.3d 1346, 1357–58 (Fed. Cir. 2013)]. Federal Circuit then addressed the evidence of unexpected results, copying, skepticism, long-felt need, and failure of others. It found all those not favoring non-obviousness except long-felt need. Court said that it agreed with Adept that the district court erred in its analysis, but this error was harmless because the evidence Adapt introduced is not sufficient to overcome the strong case of obviousness as a matter of law. At best, the asserted “longfelt need” here, as most strongly evidenced by the FDA’s statements in 2012, began just three years before the priority date of the patents-in-suit. This need, even if unmet, was not so long felt that it overcomes the strong case of obviousness, particularly in view of the plethora of prior art references discussed above identifying “intranasal naloxone as a viable means for treating opioid overdose.”