Post-filing examples, even if made by different method than prior art, may be relied upon to show inherency, particularly if patent owner fails to show that inherent feature is absent in prior art
| January 21, 2020
Hospira, Inc. v. Fresenius Kabi USA, LLC
January 9, 2020
Lourie, Dyk, Moore. Opinion by Lourie.
Summary
The CAFC upheld the obviousness of claims based on an inherency theory. In particular, the CAFC saw no fault in the conclusion that the combination of prior art possessed an inherent property even though the data demonstrating the inherent property was from post-filing examples made by a different method than the combination of cited art. This is because the patent owner failed to demonstrate any situation where the inherent property was not present.
Details
Background
Hospira is the owner of U.S. Patent No. 8,648,106. Fresenius filed an Abbreviated New Drug Application (ANDA) stipulating to infringement of claim 6 of the ‘106 patent, but arguing that this claim is invalid. Claim 6 (which depends on claim 1) recites as follows:
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.
Dexmedetomidine is a sedative that was originally patented in the 1980’s. In 1989, safety studies were performed using a 20 µg/mL dosage in humans, but were eventually abandoned due to adverse side effects.
In 1994, FDA approval was granted to market a 100 µg/mL dose of dexmedetomidine under the name “Precedex Concentrate.” Precedex Concentrate was provided in 2 mL sealed glass vials/ampoules with coated rubber stoppers. Precedex Concentrate was sold with instructions for diluting to a concentration of 4 µg/mL prior to use.
Additionally, in 2002, a 500 µg/mL “ready to use” formulation of dexmedetomidine was granted approval for veterinary use in Europe. This product was called Dexdomitor, and was stored in 10 mL glass vials sealed with a coated rubber stopper. Dexdomitor has a 2 year shelf life.
The ‘106 patent explained that the prior art dexmedetomidine was problematic due to the requirement for dilution, and disclosed a premixed, “ready to use” formulation, which can be administered without dilution. The ‘106 patent stated that the invention was based in part on the discovery that the premixed dexmedetomidine “remains stable and active after prolonged storage.” The specification included studies of dexmedetomidine potency over time under different storage conditions, such as the material of the container. Further, the specification disclosed a manufacturing method that provided nitrogen gas into the headspace of the bottle.
District Court
The district court concluded that claim 6 was obvious in view of (a) the combination of Precedex Concentrate (100 µg/mL requiring dilution) and the knowledge of a person skilled in the art, and (b) the combination of Precedex Concentrate (100 µg/mL requiring dilution) and Dexdomitor (500 µg/mL not requiring dilution). In particular, the district court focused on the “4 µg/mL preferred embodiment”: a glass container made of glass and a rubber-coated stopper with ready to use 4 µg/mL dexmedetomidine. The main issue related to the “about 2%” limitation.
The district
court concluded that the “about 2%” limitation was inherent in the prior art’s
“4 µg/mL preferred embodiment.” To reach this conclusion, the district court
relied on evidence of 20+ tested samples, all of which met the “about 2%”
limitation. The court also relied on
expert testimony that the concentration of dexmedetomidine does not impact its
stability. Further, the court relied on the fact that neither the label of
Precedex Concentrate nor the label of Dexdomitor mentions chemical
stabilizers. Importantly, the district
court found insufficient evidence that it would have been expected that a lower
concentration of dexmedetomidine would reduce stability, or that oxidation
would occur in the absence of a nitrogen gas environment. The district court concluded that dexmedetomidine
is a “rock stable molecule” and that claim 6 is therefore invalid as obvious in
view of the prior art.
CAFC
At the CAFC, the main issue raised was whether the inherency conclusion of the district court was improper because it relied on non-prior art embodiments, rather than the alleged obvious combination of prior art. In particular, the data relied upon by the district court was entirely from Hospira’s NDA for Precedex Premix and Fresenius’s ANDA product. Both of these are after the filing date of the application. Both were made using the nitrogen gas environment method as described in the specification. As such, Hospira argued that it cannot be said that the data demonstrate the inherency of a preferred embodiment which may or may not be made using this manufacturing process.
However, the CAFC agreed with Fresenius that it was not an error to point to post-filing data in support of an inherency conclusion. Although the later evidence is not prior art, it can nonetheless be used to demonstrate the properties of the prior art. The NDA and ANDA data merely served as evidence to show whether there was the decrease in concentration over time of the 4 µg/mL preferred embodiment.
Additionally, the CAFC noted that claim 6 is not a method claim or a product-by-process claim. Since claim 6 includes no limitations relating to a nitrogen gas environment in the glass container, such limitations should not be read into the claim. Thus, the district court properly ignored the process by which the samples were prepared when considering inherency.
The CAFC then highlighted that the record included evidence that concentration does not affect the stability of dexmedetomidine, and also criticized Hospira for failing to present any examples of the 4 µg/mL preferred embodiment which did not satisfy the “about 2%” limitation. Furthermore, Hospira failed to demonstrate that the reason why the 20+ examples satisfied the “about 2%” limitation was because of the nitrogen gas in the glass container, and likewise that samples made by a different method would fail to satisfy the “about 2%” limitation.
Additionally, Hospira argued that the district court applied the wrong standard to inherency by applying a “reasonable expectation of success” standard. Although the CAFC agreed that the district court conflated two issues, they found that the district court’s “unnecessary analysis” was a harmless error and does not impact the outcome of the case. In other words, if a property is inherently present, there is no further question of whether one has a reason expectation of success in obtaining this property.
Returning to the merits, the CAFC concluded that claim 6 is obvious. Since there are no other relevant limitations recited in claim 6, the mere recitation of the inherent “about 2% limitation” cannot render the claim nonobvious. Rather, the patent was merely based on a discovery that dexmedetomidine is stable after long-term storage, but does not require any additional manufacturing limitations or the like.
Takeaway
-Applicants and patent owners should be aware that post-filing data can demonstrate inherency of prior art in some situations.
-When facing an issue of inherency, the Applicant or patent owner should focus on providing evidence to demonstrate the lack of an allegedly inherent feature in some situations, rather than criticizing the experimental design of the data alleged to show inherency.
-Applicants and patent owners should take care that non-inherency arguments are commensurate in scope with the claims. Here, the patent owner should have presented evidence relating to differences between drug potency in a nitrogen gas environment (as in the data relied upon by the court) as compared to a normal air environment (as in the combination of prior art). Although the claims do not require any particular environment, such data could have shown that even if the nitrogen gas environment (not prior art) satisfied the “about 2% limitation,” the non-nitrogen gas environment (prior art) did not necessarily satisfy the “about 2% limitation.”
-Applicants should be sure to claim all disclosed important features. In this case, positively reciting the nitrogen gas environment and the container at a minimum level of detail may have been sufficient to save the claims from obviousness.
