Budesonide & Formoterol – USA

Budesonide & Formoterol – USA

On March 02, 2021, Northern District of West Virginia found Symbicort® composition patents valid in a Hatch-Waxman suit.


AstraZeneca (Plaintff) owns US 7,759,328; US 8,143,239 and US 8,575,137. These patents are listed in Orange Book (OB) for the product, Symbicort® (Budesonide & Formoterol) metered dose inhaler (pMDI). These patents claim composition containing Budesonide & Formoterol along with excipients such as HFA 227, PVP K25 and PEG-1000 with their concentrations. Mylan (Defendant) filed ANDA with USFDA seeking approval to market generic version. AstraZeneca sued Mylan.

Mylan argued that the patents-in-suit are invalid as obvious because the claimed formulations (pMDI) would have been an obvious reformulation of the Symbicort® Turbuhaler DPI. According to Mylan, a POSA would have been motivated to reformulate the Symbicort® DPI as a pMDI while maintaining its proven dosing and efficacy. Mylan argued that HFA 227 would have been the preferred non-CFC propellant of the two readily available options, and a POSA would have selected PVP and PEG as excipients based on the prior art. Finally, a POSA would have optimized excipient grades and concentrations through routine testing with a reasonable expectation of success. AstraZeneca  argued that the prior art on which Mylan relies teaches away and would not have motivated a POSA to make the claimed combination.


Court’s analysis:

Court said that there is no dispute that a POSA would have been motivated to adapt Symbicort® from a DPI to a pMDI because of preference in the US market. But given the dearth of prior art that taught towards a formulation with all of the claimed components of the claims at issue, it is unclear what would have prompted (or even enabled) a POSA at the priority date to select and combine all the elements of the claimed invention. There were certain disadvantages with the cited prior arts.


First prior art (Mistry) disclosed vast number of potential formulations. The prior art disclosed multiple grades of different excipients, different propellants, and various LABAs and inhaled corticosteroids that could be used. Therefore, without “clues pointing to the most promising combinations”, an artisan could have spent years experimenting without success. Testing these formulations to determine whether or not the combination was viable would have taken an “eternity”. Court said that Mylan’s argument amounts to simply experimenting in the “design space,” and does not consider how different amounts of various ingredients could impact each other. The record shows that the claimed amounts of the two different ingredients could and did materially and unpredictably alter the property of he claimed formulation.


Second prior art (Rogueda) teaches away from the claimed invention because the combinations closest to the claimed formulation were unsuitable and left medication residue at the gas-liquid exchange barrier. Rogueda performed tests to compare his invention containing polar fluorinated molecules to several “control” formulations.
Control 3 and Control 9 are relevant to the patents-in-suit because Control 3 contained formoterol, 0.001% w/w PVP K25, 0.1% w/w PEG-1000 in a density-matched blend of HFA 227 and HFA 134a, and Control 9 contained budesonide, 0.001% w/w PVP K25 and 0.3% w/w PEG-1000 in HFA 227. The claimed formulation at issue in this case
contains budesonide, formoterol, 0.001% w/w PVP K25, 0.3% w/w PEG-1000, and HFA 227. The expert testimony at trial, however, established that formulations with budesonide or formoterol and PVP K25 and PEG-1000 adhered to the test cans at the gas-liquid interface and had particle aggregation. Thus, making formulation unsuitable.


Here, based on the prior art available at the priority date, there was no finite number of identified, predictable solutions. Moreover, prior art taught away from claimed combination. Therefore, a POSA would not have had a reasonable expectation of success in creating a stable budesonide pMDI using HFA 227, PVP K25, and PEG-1000, much less when these ingredients were combined with formoterol.

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