BREATHE EASIER, THE CAFC PROVIDES GUIDANCE ON CONSTRUING THE CLAIMED CONCENTRATION OF A STABILIZER IN PATENTS FOR AN ASTHMA DRUG
| February 25, 2022
AstraZeneca v. Mylan Pharmaceuticals
Decided December 8, 2021
Taranto, Hughes, and Stoll. Opinion by Stoll. Dissent by Taranto
Summary:
AstraZeneca sued Mylan for infringement of its patents covering Symbicort pressurized metered-dose inhaler (pMDI) which is used for treating asthma. At issue in this case is how to construe the limitation “PVP K25 is present at a concentration of 0.001% w/w.” The district court construed the concentration using the ordinary standard scientific convention using only one significant figure to encompass the range from 0.0005% to 0.0014%. Based on this construction, Mylan stipulated to infringement. The district court then held a trial on validity and upheld the validity of the asserted claims. The CAFC affirmed the district court’s judgment of validity. But the CAFC disagreed with the construction of the concentration limitation. The CAFC held that the construction of the term should be narrower than the range provided by the ordinary meaning due to disclosures in the specification and arguments and amendments in the prosecution history. The CAFC construed the noted concentration of 0.001% to include the narrower range of 0.00095% to 0.00104%. Thus, the CAFC vacated the judgment of infringement and remanded for further proceedings on infringement.
Details:
The patents at issue in this case are U.S. Patent Nos. 7,759,328; 8,143,239; and 8,575,137 which cover the asthma inhaler Symbicort pMDI. A pMDI inhaler uses a propellant gas that is in liquid form under pressure in the pMDI device. When the inhaler is activated, the propellant causes the gas to come out as a spray making it easier to deliver the medication to the lower lungs. The representative claim is provided:
13. A pharmaceutical composition comprising
formoterol fumarate dihydrate, budesonide, HFA227, PVP K25, and PEG-1000,
wherein the formoterol fumarate dihydrate is present at a concentration of 0.09 mg/ml,
the budesonide is present at a concentration of 2 mg/ml,
the PVP K25 is present at a concentration of 0.001% w/w, and
the PEG-1000 is present at a concentration of 0.3% w/w.
Mylan appealed the district court’s stipulated judgment of infringement asserting that the district court erred in the construction of the concentration of PVP K25 of 0.001%. Mylan also appealed the district court judgement of nonobviousness.
The CAFC stated that as a matter of standard scientific convention, the noted concentration of 0.001% being expressed with only one significant digit would ordinarily encompass a range from 0.0005% to 0.0014%. AstraZeneca argued that this ordinary meaning controls absent lexicography or disclaimer. However, the CAFC stated that this is an acontextual construction that does not consider disclosures in the specification and arguments/amendments in the prosecution history. The CAFC stated that “[c]onsistent with Phillips, therefore, we must read the claims in view of both the written description and prosecution history.”
The CAFC stated that the testing evidence in the specification and prosecution history demonstrates that minor differences as small as ten thousandths of a percentage (four decimal places) in the concentration of PVP impact stability. The specification repeatedly describes formulations containing 0.001% PVP as providing the best suspension stability. This is also demonstrated in the data provided in the specification. The data includes formulations including PVP at concentrations of 0.0001%, 0.0005%, 0.001%, 0.01%, 0.03%, and 0.05%. The results show that the formulation containing 0.001% PVP was the most stable and that the formulation containing 0.0005% was one of the least stable formulations. The CAFC concluded that this data shows that PVP concentration of 0.001% is more stable than formulations with slight differences in PVP concentration (e.g., a concentration of 0.0005%, and that differences down to the ten-thousandth of a percentage (fourth decimal place) matters for stability.
In the prosecution history, the Applicant amended the claims to change ranges of the concentration to recite the exact concentration of PVP to 0.001% without using the qualifier “about,” and emphasized that 0.001% was critical to stability. The CAFC also stated that Applicant knew how to claim ranges and describe numbers with approximation using the term “about,” but the Applicant chose to claim the exact value. The CAFC concluded that this supports construing 0.001% narrowly, but that there should be some room for experimental error in the PVP concentration. The CAFC stated that the margin of error that is best supported by the intrinsic record is variations in the PVP concentration at the fourth decimal place (0.000095% to 0.000104%).
AstraZeneca argued that Mylan’s proposed construction is an attempt to limit the scope of the claims to the preferred embodiment. However, the CAFC stated that AstraZeneca’s proposed construction would read on two distinct formulations described in the specification (0.0005% PVP and 0.001% PVP), but the Applicant chose to claim only one of these formulations. The CAFC also stated that Applicant cancelled claims that included the 0.0005% PVP concentration and that this provides evidence that the formulations containing 0.0005% PVP are not within the scope of an asserted claim.
Regarding the nonobviousness determination by the district court, Mylan argued that the district court erred in finding that the prior art reference Rogueda taught away from the claimed invention. The CAFC citing Meiresonne v. Google, Inc., 849 F.3d 1379 (Fed Cir. 2017), stated that “a prior art reference is said to teach away from the claimed invention if a skilled artisan ‘upon reading the reference, would be discouraged from following the path set out in the reference, or would be led in a direction divergent from the path that was taken’ in the claim.”
The Rogueda reference included control formulations to compare with its novel formulations. Mylan relied on some of the control formulations as rendering the claims obvious. Rogueda disclosed that the novel formulations provided a “drastic” reduction in the amount of drug adhesion compared to the controls.
Mylan, citing Meiresonne, argued that the court’s precedent regarding “teaching away” is that a reference “that merely expresses a general preference for an alternative invention but does not criticize, discredit, or otherwise discourage investigation into the claimed invention does not teach away.” Mylan argued that Rogueda merely expresses a preference for the novel formulations over the control formulations citing a statement in the district court opinion that “Rogueda did not necessarily disparage the formulations in Controls 3 and 9.” However, AstraZeneca provided expert testimony stating that a skilled artisan looking at the adhesion results in Rogueda would conclude that the control formulations “were not suitable” and “clearly don’t work.” The district court credited the expert testimony that a skilled artisan would have known that the control formulations were unsuitable, and thus, discouraging investigation into these formulations, and concluded that Rogueda teaches away and does not render the claims obvious. The CAFC stated that there was no clear error in the district court’s determination and affirmed the validity of the claims.
Dissent
Judge Taranto dissented from the claim construction opinion. Judge Taranto stated that 0.001% should be construed to have its significant-figure meaning of 0.0005% to 0.0014% with the possibility of shrinking the lower end of the range to exclude the overlap area between the significant-figure interval of 0.001% (0.0005% to 0.0014%) and the significant-figure interval of 0.0005% (00045% to 0.00054%). Thus, if this exclusion is applied, the range would be 0.00055% to 0.0014%.
Judge Taranto takes the position that nothing in the specification or prosecution history warrants departing from the ordinary meaning. Judge Taranto pointed out that the specification, when referring to the formulations that were tested, states that several of the formulations were “considered excellent” and that the formulation with 0.001% PVP “gave the best suspension ability overall.” In the prosecution history, the Examiner stated the need for the Applicant to show criticality by showing unexpected results of a 0.001% concentration level compared to concentration levels “slightly greater or less” than 0.001% PVP. But it is unclear if the Examiner meant to include 0.0005% and other tested concentration levels tested within the meaning of “slightly greater or less.” The Examiner’s statement about criticality does not exclude 0.0005%.
Judge Taranto also stated that changing “0.001%” having one significant figure to “0.0010%” having two significant figures (as proposed by Mylan and adopted by the majority) requires rewriting the claim term, and that this rewriting is counter to the specification and prosecution history. The specification and prosecution history uniformly used only one significant figure when referring to PVP concentration. Just because four decimal places were used for some PVP concentrations does not mean that all concentration values should be read to express a degree of precision to four decimal places. The specification uses four decimal places to refer to the absolute concentration level in examples where this is unavoidable such as for 0.0001% and 0.0005%. However, absolute levels and degrees of precision are distinct.
Judge Taranto also addressed the fact that the range implied by 0.001% overlaps the range implied by 0.0005%. Judge Taranto stated that the overlap does not support adding an extra significant digit. Judge Taranto stated that “the most this overlap could possibly support would be an exclusion of the small range with the one significant-figure interval for which there is overlap resulting in the range of 0.00055% to 0.0014%. However, Judge Taranto pointed out that Mylan’s product is still within this narrower range, and thus, it is not necessary to decide whether the overlap-area exclusion is justified as a claim construction.
Comments
The majority appears to have been swayed by the fact that a formulation within the range of the ordinary meaning of the claimed concentration provided significantly different results. What is not clear is whether these different results, while not the best, could still be considered good. Judge Taranto pointed out that the specification stated that several of the tested formulations were considered excellent while the 0.001% was the best. When drafting and prosecuting patent applications, you need to be aware that your experimental data and amendments to the claims can be used to narrow the range afforded by the ordinary meaning of a certain value.
With regard to arguing non-obviousness due to a teaching away in the prior art, expert testimony can be critical and should be used to support your argument whether you are defending the validity of a patent or trying to invalidate.
