IP Law Daily, PATENT—D. Del.: Hospira’s proposed generic Adrenalin® epinephrine injection infringed valid patents held by Par, (Nov 18, 2019)

By Joseph Arshawsky, J.D.

Following a bench trial, the court found all limitations of the patents-in-suit were met literally or by the doctrine of equivalents.

Defendant Hospira Inc.’s ("Hospira") filing with the FDA of an Abbreviated New Drug Application ("ANDA") seeking approval to manufacture a generic version of Plaintiffs Par Pharmaceutical, Inc., Par Sterile Products, LLC, and Endo Par Innovation Company, LLC’s (collectively, "Par") Adrenaline® brand epinephrine injections infringed Par’s U.S. Patent Nos. 9,119,876 (the "’876 patent") and 9,295,657 (the "’657 patent"), the federal district in Wilmington, Delaware has ruled. The court further found that the ‘876 patent and ‘657 patent were valid and not obvious. There was no motivation to combine the prior art references, and years of failure demonstrated nonobviousness (Par Pharmaceutical, Inc. v. Hospira, Inc., November 14, 2019, Bataillon, J.).

This patent infringement action was brought under the Hatch-Waxman Act. Hospira filed an ANDA with the FDA seeking approval to engage in the manufacturing and sale of a generic version of the Par’s Adrenalin® brand epinephrine injection 1 mg/mL product, which is indicated for emergency treatment of allergic reactions, including anaphylaxis. The dispute between the parties involves injectable epinephrine formulations and long-standing problems of stability and shelf-life. On December 7, 2012, Par’s Adrenalin® was the first epinephrine injection product approved by the FDA for use in a clinical setting available in the United States. Par’s efforts to improve the 2012 FDA-approved product eventually led to a supplemental that was approved on September 12, 2016, and to the two patents that are the subject of this case.

The patents-in-suit. Par’s predecessor, JHP, filed Application Serial No. 14/657,990 with the PTO on March 13, 2015, and it issued as the ’876 patent on September 1, 2015. JHP filed Application Serial No. 14/818,121 with the PTO on August 4, 2015, and it issued as the ’657 patent on March 29, 2016. Id. at 3. The ’657 patent is a continuation of the application that issued as the ’876 patent. Both patents are titled "Epinephrine Formulations." The ’657 patent and the ’876 patent share a common specification. The ’876 patent covers the composition of the inventive formulations and the improved impurity profile. The ’657 patent covers using those formulations to treat patients. In addition to challenging infringement, Hospira challenged the validity of Par’s patents. In its challenge to the validity of the patents, Hospira contends that the asserted claims of the ’876 patent would have been obvious to a person of ordinary skill in the art as of the priority date in light of several combinations of prior art references. The court held a bench trial from June 28 to July 3, 2019, and the court issued its findings of fact and conclusions of law finding the patents-in-suit valid and infringed.

Infringement. The '876 patent claims are directed to compositions comprising: (1) epinephrine, (2) a tonicity regulating agent, (3) a pH raising agent, (4) an antioxidant comprising sodium bisulfite and/or sodium metabisulfite, (5) a pH lowering agent, and (6) a transition metal complexing agent, in certain ranges. The court found that Par demonstrated by a preponderance of the evidence that Hospira’s ANDA product infringes each of the asserted claims of the patents-in-suit.

The word "about" does not have a universal meaning in patent claims, and its meaning depends on the technological facts of the particular case. In an earlier order, the court noted that scope of "about" "is not a strict numerical boundary to the specified parameter," but rather "must be determined using a functional approach" and "requires a factual inquiry as to the purpose of the limitation." That functional approach and factual inquiry leads to the conclusion that the limitation, qualified as it is to "about 6 to 8 mg/mL of sodium chloride," covers Hospira’s ANDA product. There is no dispute that the sodium chloride in the Hospira ANDA product is a tonicity regulating agent, the main dispute is how much is required. Par's expert testimony was uniformly targeted to address the technological context, the criticality of the range, and the purpose of the limitation, whereas Hospira’s experts focused largely on linguistics and semantics. The court credited Par’s experts’ testimony on this topic over Hospira’s experts.

Equivalency. The evidence shows that the amount of 8.55 and 9 mg/mL sodium chloride is equivalent to "about 8 mg/mL" of a tonicity regulating agent, and the amount of 2.41 and 2.57 mg/mL is equivalent to ‘about 2.8 mg/mL" pH raising agent under a function-way-result analysis. The court also credits Par’s expert with respect to his transition metals complexing agent analysis. Hospira’s expert acknowledged that transition metals are variable and not subject to control. The court found the relevant comparison is to the product that an ANDA applicant seeks permission to sell, not to its representative batches. Hospira represented to the FDA that the citrate ion in their proposed product performs the very function described in the ’876 patent specification.

Invalidity. Hospira failed to show, by clear and convincing evidence, that a person of ordinary skill in the art would have had a motivation to combine or modify the teachings of the combinations of references relied upon by Hospira’s expert to arrive at the subject matter claimed in the asserted claims and would have had a reasonable expectation of success in doing so. Nor did it prove that evidence of objective indicia of non-obviousness, including long-felt need, failure of others, recognition of the problem, teaching away, skepticism of others, and unexpected results, support the non- obviousness of the asserted claims.

The long-standing failure of others to develop similar epinephrine formulations with long-term stability supports a finding that the patented formulation was not obviousness. The record shows that there was a need for a stable formulation as recently as 2013, despite the fact that epinephrine degradation had been studied since the 1960’s. Both Par and Hospira engaged in lengthy development efforts with repeated failures and scientists at both companies expressed the unexpected difficulty of developing long-term stable epinephrine formulations. Hospira failed to prove by clear and convincing evidence that the asserted claims of the patents-in-suit are invalid. The court credited Par’s expert’s testimony that the prior art teaches away from the combination and agrees that a person of ordinary skill in the art would not be motivated to improve on a product that had already been approved.

The motivation provided to Par in the FDA’s request was not public, nor is there evidence that the fact was known to Hospira scientists at the time no motivation to combine. Prior art teaches away from essentials of the formula. The court also rejected Hospira’s reliance on the disclosure-dedication rule. Hospira did not show that the subject matter of Hospira's ANDA was surrendered to the public by the patentee because it is disclosed in the specifications of the patents-in-suit but is not encompassed in the claim language. The court found Hospira’s expert’s testimony on that subject was not credible and credited Par’s experts’ testimony to the contrary.

This case is No. 1:17-cv-00944-JFB-SRF.

Attorneys: Steven J. Fineman (Richards, Layton & Finger, PA) for Par Pharmaceutical, Inc. John C. Phillips, Jr. (Phillips, Goldman, McLaughlin & Hall, PA) for Hospira, Inc.

Companies: Par Pharmaceutical, Inc.; Hospira, Inc.

Cases: Patent DelawareNews