Formoterol and Budesonide – USA

Formoterol and Budesonide – USA

On Dec. 08, 2021, Federal Circuit affirmed validity and remanded infringement determination of district court.

 

AstraZeneca sued Mylan for infringement of all claims of U.S. Patent Nos. 7,759,328; 8,143,239; and 8,575,137 patents because Mylan filed ANDA seeking approval to market generic version of Symbicort® pMDI (Formoterol and Budesonide). After claim construction, Mylan stipulated to infringement but contested invalidity. District court concluded the infringement and validity of these patents. Mylan appealed from the stipulated judgment of infringement and the final judgment of no invalidity. First, Mylan challenged the district court’s claim construction of “0.001%,” the claimed amount of the excipient PVP. Second, Mylan challenged several factual findings underlying the district court’s determination of nonobviousness. The asserted claims are directed to pharmaceutical compositions comprising formoterol fumarate dihydrate and budesonide, as well as a number of inactive ingredients at specified concentrations. The inactive ingredients include HFA 227 (a propellant), PVP K25 (a formulation stabilizer), and PEG-1000 (a lubricant).

 

Infringement:

Federal Circuit said that the dispute here is whether the concentration of PVP being “0.001%” means 0.001% within one significant figure—encompassing a concentration of PVP in the range of 0.0005% to 0.0014%, as AstraZeneca contends and as the district court construed this term—or it has a narrower meaning in view of the specification and the prosecution history—precisely 0.001% w/w PVP with only “minor variations,” as Mylan contends. Federal Circuit further said that both the written description and prosecution history place considerable emphasis on the stability of the claimed formulations, i.e., formulations with 0.001% w/w PVP, compared to formulations with slightly higher or slightly lower concentrations of PVP, including for example, 0.0005% w/w. Thus, taken as a whole, the intrinsic record supports a narrower construction of 0.001% to reflect that term’s application to the PVP concentration in particular, and the testing evidence in the written description and prosecution history showing that very minor differences in the concentration of PVP—down to the ten-thousandth of a percentage (fourth decimal place)—impact stability. Thus, while an acontextual read of the term 0.001% might encompass amounts of an excipient or active ingredient between 0.0005% and 0.0014%, the written description suggests that the claimed formulations with 0.001% w/w PVP were intended to be more exact such as with only minor variations in the PVP concentration at the fourth decimal place 0.00095% to 0.00104%. This construction is also supported by the prosecution history. During prosecution when Examiner rejected the claim then in response, the inventors asserted that the “criticality of 0.001% w/w PVP in a formulation containing 2 mg/ml budesonide” was illustrated by the data provided in the written description—specifically, Figures 3 and 5—which compared the stability of a 0.001% w/w PVP formulation to formulations with 0.0001%, 0.0005%, 0.01%, 0.03%, and 0.05% w/w PVP. Over the course of the prosecution history, the inventors narrowed the claimed concentration of PVP to 0.001% w/w from a broader range without using the qualifier “about.” Federal Circuit therefore vacated the stipulated judgment of infringement and remanded to find in the first instance whether Mylan’s ANDA Product infringes the asserted claims under the proper claim construction.

 

Invalidity:

Mylan argued on appeal that several factual findings underlying the district court’s nonobviousness determination are clearly erroneous, including its finding that the prior art reference Rogueda taught away from the claimed invention. Federal Circuit said that the district court properly relied on expert testimony regarding how a skilled artisan would interpret the data in Rogueda to find implicit disparagement. The district court credited Dr. Young’s
testimony that a person of ordinary skill in the art would have known that the control formulations were unsuitable
for further experimentation, thus “discouraging investigation into” these formulations. Federal Circuit thus did not find clear error in district court’s finding.

 

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