Hospira, Inc. v. Fresenius Kabi USA, LLC (Fed. Cir. 2020)

By Kevin E. Noonan --

It seems that memes can be as compelling in the law as in social media, and the meme of the moment in patent law is inherency, particularly as applied to obviousness determinations (see, for example, Persion Pharmaceuticals LLC v.  Alvogen Malta Operations Ltd.; Acorda Therapeutics, Inc. v. Roxane Labs., Inc.).  This tendency was most recently illustrated in the Federal Circuit's decision in Hospira, Inc. v. Fresenius Kabi USA, LLC.

The issue arose in ANDA litigation, where the District Court found claim 6 of U.S. Patent No. 8,648,106 to be obvious:

6.  A ready to use liquid pharmaceutical composition for parenteral administration to a subject, comprising dexmedetomidine or a pharmaceutically acceptable salt thereof disposed within a sealed glass container, wherein the liquid pharmaceutical composition when stored in the glass container for at least five months exhibits no more than about 2% decrease in the concentration of dexmedetomidine, wherein the dexmedetomidine or pharmaceutically acceptable salt thereof is at a concentration of about 4 μg/mL.

(Wherein the italicized portion of the claim is recited expressly in independent claim 1, from which claim 6 depends.)

The claim encompasses Hospira's Precedex (dexmedetomidine) product, a sedative, first developed in the 1980's.  However, its earliest developer (Farmos) had difficulty getting FDA approval, and it was later sold by Abbott as a concentrate (at a concentration of 100 micrograms/mL) in 2mL vials, that needed to be diluted for use at a concentration of 4 micrograms/mL (the prevailing belief being that the drug was unstable at its therapeutically effective concentration.  Hospira determined that it could be prepared at the lower concentration, the inventors having discovered that the diluted formulation was stable and active over a prolonged period of time, with there being some evidence that nitrogen sparging was important to confer the stability properties.  The advantages of the invention (i.e., not needed to be dilutes at point of care) included avoidance of errors/overdose, greater convenience, and reduced frequency of contamination, among others.

The District Court held claim 6 to be obvious over the prior art concentrate and knowledge of one having skill in the art.  The Court further depended on the 4 microgram/mL formulation being expressly taught in the prior art with the sole distinction recited in the claim being the "less than 2% degradation limitation," which the Board held was an inherent property of the 4 microgram/mL embodiment.  The District Court considered fact and expert testimony, specifically defendant expert's testimony (disputed by Hospira) regarding that the concentration of the drug had no effect on stability.  The basis for the District Court's decision was synopsized in the Federal Circuit's opinion:

A [person of ordinary skill in the art] would have a considerable understanding of organic chemistry.  Based on his or her understanding of the chemical properties of dexmedetomidine, a [person of ordinary skill in the art] would have expected it to be stable in room-temperature storage conditions for at least five months (based presumably on evidence adduced at trial).

The Court heard (ultimately persuasive) expert testimony that the chemical structure of dexmedetomidine would be "a rock stable molecule" under normal conditions based on its aromatic ring structure and lack of hydrolyzable and oxidizable groups.

The Federal Circuit affirmed, in an opinion by Judge Lourie, joined by Judges Dyk and Moore.  The Court affirmed the District Court's application of the inherency doctrine as applied to its obviousness determination, noting that inherency is established in the context of obviousness when "the limitation at issue necessarily must be present, or the natural result of the combination of elements explicitly disclosed by the prior art" and that Fresenius had satisfied this standard.

On appeal, Hospira argued that the evidence that the 2% limitation was inherent was adduced from samples made according to the patent disclosure, and thus not prior art; the weakness of this argument is that inherency almost by definition arises where the inherent property existed in the prior art but was not appreciated in the art.  The opinion notes that, as here, "extrinsic evidence can be used to demonstrate what is 'necessarily present' in a prior art embodiment even if the extrinsic evidence is not itself prior art," citing Monsanto Tech. LLC v. E.I. DuPont de Nemours & Co., 878 F.3d 1336, 1345 (Fed. Cir. 2018), and Schering Corp. v. Geneva Pharm., Inc., 339 F.3d 1373, 1377 (Fed. Cir. 2003).  In addition, the opinion states that "the work of the inventor or the patentee can be used as the evidence of inherency," citing Alcon Research, Ltd. v. Apotex Inc., 687 F.3d 1362, 1369 (Fed. Cir. 2012), and Telemac Cellular Corp. v. Topp Telecom, Inc., 247 F.3d 1316, 1327–28 (Fed. Cir. 2001).

An important aspect of the Federal Circuit's opinion is that "[t]he inherent teaching of a prior art reference is a question of fact," Par Pharm. v. TWI Pharm., Inc., 773 F.3d 1186, 1194 (Fed. Cir. 2014), and under the standard of review for fact issues (clear error), the District Court's fact determinations are entitled to substantial (almost plenary, in practice) deference.  The opinion sets forth the importance of this deference explicitly:

Hospira's arguments on appeal cannot change the trial record, which included more than 20 samples that all met the about 2% limitation.  The trial record also included testimonial and statistical evidence that dexmedetomidine is a very stable drug at any concentration; thus, simply adding solvent to dilute it by a factor of 25—from 100 μg/mL, which was known to be stable, to 4 μg/mL—does not affect its inherent stability.  On that record, it was not clearly erroneous for the district court to find that the about 2% limitation was necessarily present in the prior art.

The opinion particularly notes regarding Hospira's failure to rebut the application of inherency principles that "Hospira did not present evidence of even a single sample of the 4 μg/mL preferred embodiment that failed to meet the about 2% limitation."

Another issue Hospira raised against the District Court's decision related to the interplay between the inherency standard and obviousness determination with regard to the requirement that there be a reasonable expectation of success.  To the extent that the District Court erred the Court said it was harmless error, specifically because the Court "engag[ed] in unnecessary analysis in evaluating whether the chemical properties of the dexmedetomidine molecule, the information in the Precedex Concentrate and Dexdomitor labels, and the industry guidance for stability testing would enable a person of ordinary skill to have had a reasonable expectation of successfully achieving the about 2% limitation."  Presumably the panel's basis for this analysis of because once the inherent property is appreciated or discovered that would supply the reasonable expectation of success.

Finally, the opinion notes that, as in many cases, disclosure in the patent specification (in hindsight) provides support for the argument that the claims are invalid:

Here, the '106 patent itself states that the invention was based on "the discovery that dexmedetomidine prepared in a premixed formulation . . . remains stable and active after prolonged storage."  '106 patent, col. 3 ll. 6–10 (emphasis added).

In addition to the promulgation of the idea that inherency is available to be used to support for obviousness, this decision makes clear that the Court (or some members of the Court) is of a mind to consider claims in a restrictive, rather than permissive way.  It is clear that like "mere" isolation in other contexts the discovery of novel properties, not appreciated in the prior art will be treated as inherently present in the art and thus can be used for determining obviousness.  This tendency has support in earlier Federal Circuit decisions (for example, that "[i]t is well-settled that the inclusion of an inherent, but undisclosed, property of a composition does not render a claim to the composition nonobvious," Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342, 1347 (Fed. Cir. 1999)) but its extension to obviousness under the recent case law indicates that prudence suggests applicants limit statements of discoveries as the basis for their inventions and to include some evidence that claims to an invention, like this one, contain limitations that distinguish over any inherent properties (e.g., by reciting the need for treating the diluted formulation by nitrogen sparging).  Doing so might (just might) provide a basis for asserting that what provokes or illustrates the inherent property was itself not inherent and thus preclude determining that the invention is obvious.

Hospira, Inc. v. Fresenius Kabi USA, LLC (Fed. Cir. 2020)
Panel: Circuit Judges Lourie, Dyk, and Moore
Opinion by Circuit Judge Lourie

Comments

[Atari Man]

As I wrote a few weeks ago in response to the Persion decision:

There's some sense to the concept of "inherent anticipation", but "inherent obviousness" is a logical impossibility. When are these judges going to learn to admit they're wrong and stop perpetuating inanities just because some of their colleagues got it wrong in the past?

I'm not surprised to see this from Judges Dyk and Lourie, but it's disappointing to see Judge Moore go along with this balderdash.