Keeping Up With Life Sciences Appeals: 1Q2020

Authored by: Betsy Flanagan, Ryan Petty, and Veena Tripathi

The Federal Circuit's life sciences decisions in 1Q2020 addressed issues of claim construction, anticipation, prosecution history estoppel, and eligibility.  These decisions help clarify how "comprising" transitional phrases in claims interact with closed Markush group limitations, confirm that post-priority date evidence can establish inherent limitations in prior art, and emphasize that the a POSA's understanding of the prior art determines whether a limitation is missing, among others.

"Comprising" Claims Do Not Exclude Unrecited Markush Group Compounds: Amgen Inc. v. Amneal Pharms. LLC, 945 F.3d 1368 (Fed. Cir. 2020)

In Amgen Inc. v. Amneal Pharms. LLC,[1] the Federal Circuit held that a "comprising" claim requires the presence of a recited Markush group compound but does not exclude the presence of an unrecited Markush group member.

This Hatch-Waxman case involves Amneal, Piramal, and Zydus's proposed generic version of Amgen's hyperthyroidism treatment, Sensipar®.  Asserted claim 1 of U.S. Patent No. 9,375,405 is directed to "[a] pharmaceutical composition comprising...(d) from about 1% to about 10% by weight of at least one disintegrant selected from the group consisting of crospovidone, sodium starch glycolate, and croscarmellose sodium."[2]

At the district court, Amgen argued the Markush groups should be open to unrecited elements.[3]  The district court, relying on Multilayer Stretch Cling Film Holdings, Inc. v. Berry Plastics Corp.,[4] disagreed and found that Amgen had not met the "very strong presumption" that a Markush group is closed to unrecited compounds. After a bench trial, the district court held that Amneal's product did not satisfy the disintegrant limitation, because while it did use crospovidone, it included also an additional disintegrant (pregelatinized starch).[5]

The Federal Circuit panel (Newman, Lourie, and Taranto) reached a different claim construction.[6]  The panel explained that Multilayer did not stand for the broad proposition that "consisting of" Markush group language preceded by a "comprising" transition phrase precludes all components outside the group that perform the general function of the particular limitation.[7]  Specifically, the claim limitation at issue in Multilayer was directed to "five identifiable layers, with each layer being selected from the group consisting of" four different resins, where the resins were various polymers of ethylene and alpha olefins.[8]  Because the limitation had defined the resins in the five layers with "consisting of" language, an unrecited resin in the layers would result in non-infringement.[9]  The court in Multilayer had not even relied on the impact of the "comprising" transitional phrase at the start of the claim in construing the Markush group limitation.[10]

In contrast, the Amgen panel found "[t]he plain language of [the '405 patent's] claim requires 'at least one' of the Markush group members and certainly does not indicate that the only ... disintegrants in the claimed formulation are those listed in the groups."[11]  Because the district court had relied on an erroneous claim construction, the panel vacated the finding of non-infringement and remanded.[12]

Post-Priority Date Evidence Can Prove Inherency: Hospira, Inc. v. Fresenius Kabi USA, LLC, 946 F.3d 1322 (Fed. Cir. 2020)

In Hospira, Inc. v. Fresenius Kabi USA, LLC,[13] the Federal Circuit affirmed an obviousness finding that relied on post-priority date evidence to establish an inherent feature of a prior art embodiment.

This Hatch-Waxman case concerned Hospira's Precedex Premix product, a formulation of the sedative dexmedetomidine for intravenous injection.  Prior art compositions of the drug were concentrated, requiring dilution to 4 μg/mL prior to administration, which presented several safety issues.  Claim 6 of Hospira's '106 patent covered a ready-to-use formulation of 4 μg/mL dexmedetomidine that "when stored in the glass container for at least five months exhibits no more than about 2% decrease in the concentration or dexmedetomidine."[14]

In support of obviousness, Fresenius Kabi relied on a particular 4 μg/mL embodiment that was expressly disclosed in the prior art, and sought to prove inherency of the "about 2%" claim limitation.  To do so, the defendant presented post-priority date evidence that each of more than 20 tested samples of that particular 4 μg/mL embodiment met the "about 2%" limitation, which derived from the Hospira's NDA and the Fresenius Kabi's ANDA.  The district court found that evidence established inherency by clear and convincing evidence.[15]

On appeal, Hospira argued that the district court erred in considering the inherent properties of the non-prior art embodiment, i.e. the data related to the 4 μg/mL formulation.  The panel (Lourie, Dyk, Moore) rejected this argument.  It articulated that "[e]xtrinsic 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," and such evidence can include the "work of the inventor or the patentee."[16]  The panel then found no clear error with the district court's factual finding that the "about 2% limitation was necessarily present in the 4 μg/mL preferred embodiment."[17]  In doing so, it reiterated Hospira's lack of evidence of "even a single sample" of the preferred embodiment that failed to meet the about 2% limitation.[18]

Interestingly, in a separate litigation, the District of Delaware held the '106 patent valid.  Presented with a different evidentiary record, the Court found the "about 2%" limitation not inherent in the 4 μg/mL embodiment.[19]

Hospira showcases that post-priority date evidence is available to elucidate what is actually in the prior art.  Though Fresenius Kabi used already existing data to demonstrate inherency, testing data generated during litigation could be used by patentee or defendant in support of or against inherency.

No Combining References for Inherency: Galderma Labs., L.P. v. Teva Pharms. USA, Inc., 2020 U.S. App. LEXIS 2811 (Fed. Cir. Jan. 29, 2020)

In Galderma Labs., L.P. v. Teva Pharms. USA, Inc. (non-precedential),[20] the Federal Circuit reversed and remanded a district court's finding of anticipation based on the use of multiple prior art references in an inherency analysis.

This Hatch-Waxman case concerned the drug Soolantra®, and the asserted claims covered methods of treating inflammatory lesions of rosacea by topically administering 1% ivermectin, and also required certain "efficacy benchmarks" from the treatment.[21]  Teva stipulated to infringement, but asserted that the claims at issue were invalid for anticipation and obviousness.[22]

The district court found the claims anticipated by U.S. Patent No. 5,952,372 ("McDaniel"), and did not reach Teva's other anticipation and obviousness defenses[23]  The key issue was whether McDaniel disclosed an "ivermectin formulation (such as Soolantra®) that necessarily achieve[d] the efficacy limitations."[24]  The district court found it did, based on the parties' stipulation that a skilled artisan would have been able to practice McDaniel's treatment method with the formulation from another reference called Manetta U.S. Patent No. 7,550,440, which undisputedly disclosed the Soolantra formulation. Id. at 6.

On appeal, the panel (Moore, O'Malley, and Stoll) reversed and remanded, concluding that the district court erred by finding the asserted claims anticipated based on disclosures from both the McDaniel and Manetta references.  The panel emphasized that anticipation requires "a single prior art reference [that] discloses each and every limitation of the claimed invention, either expressly or inherently," and "turning to another reference for a 'very specific teaching'" contradicted this longstanding principle.[25]  The panel also found the district court erred by conflating enablement and anticipation.  The panel reasoned that though the parties stipulated that a POSA "would have been able to practice the general formulations disclosed in McDaniel," the stipulation cannot mean the prior art inherently disclosed the specific, missing limitation.[26]

The panel found Bristol-Myers Squibb Co. v. Ben Benue Labs.[27] instructive. In Bristol-Myers, the district court's finding of anticipation was proper where the "asserted anticipatory reference contained the very disclosure that was found to be enabling based on other references."[28]  By contrast, the Galderma panel found that the asserted anticipatory reference did not contain the specific disclosure that was necessary for a finding of anticipation and refused to incorporate Manetta.[29]

The panel also found the district court's determination of inherent anticipation on the basis of "mere possibility" erroneous.[30]  The inquiry was whether the "claimed efficacy limitations 'necessarily result' from practicing McDaniel."[31]  The panel concluded the limitations did not necessarily result from practicing the prior art because "(1) McDaniel did not disclose the specific Soolantra® formulation; and (2) as Teva's expert acknowledged, variation in formulation parameters will undoubtedly affect the results achieved from the use of McDaniel's disclosed formulations."[32]  The panel found the district court's inherency finding clearly erroneous because there was "no basis for [the panel] to conclude with certainty that all 1% formulations within the scope of McDaniel's disclosure will inevitably achieve the claimed efficacy limitations."[33]

The panel reversed and remanded for consideration of Teva's remaining invalidity defenses, including obviousness over Manetta or the combination of McDaniel, Manetta and other prior art references.[34]

Whether Limitation Is Missing Depends on POSA's Understanding of Prior Art: Genentech, Inc. v. Hospira, Inc., 946 F.3d 1333, 1340 (Fed. Cir. 2020)

In Genentech, Inc. v. Hospira, Inc.,[35] the Federal Circuit emphasized that the test for whether a claim limitation is missing in an anticipatory reference is if a skilled artisan would "reasonably understand or infer" that the prior art reference teaches every claim limitation.[36]

Genentech's '799 patent claims a method for purifying an antibody by Protein A chromatography from about 10 °C to about 18 °C.[37]  The specification teaches that running the purification at a lower temperature reduces the amount of Protein A that leaches into the eluent, thus reducing contamination of the antibody solution.[38] The claims, however, do not specifically recite this relationship.[39]

Hospira sought IPR of the '799 patent, asserting that claim 1 was anticipated and rendered obvious by WO '389, which teaches purification of an antibody by Protein A chromatography where "[a]ll steps are carried out at room temperature (18-25 °C)."[40]  The Board, crediting Hospira's expert, found that a POSA would assume "all steps" meant that both the cell culture supernatant loaded onto the column and the column itself were maintained at the disclosed temperature range, absent specific direction to the contrary.[41]  The overlap of the prior art and claimed range—at 18 °C would result in anticipation unless Genentech could demonstrate the claimed range is critical to the operation of the invention.[42]  The Board, again crediting Hospira's expert, found that Protein A chromatography functions the same at a variety of temperatures.[43]  And because Protein A leaching, like other proteolysis, decreased with decreasing temperature, a POSA would expect that using temperatures below the claimed range (e.g., 4 °C), would further reduce leaching.  Therefore, the claimed range was not critical to practicing the invention.[44]

The panel majority (Chen and Prost) affirmed.  Interestingly, Genentech did not challenge the Board's finding on criticality.[45]  Instead, Genentech argued that the supernatant applied to the Protein A column in WO '389 would not have been at room temperature, but instead at 37 °C, the temperature at which cells are typically cultured.[46]  The panel majority found that the Board was well within its discretion to credit Hospira's expert over Genentech's on the issue of the supernatant temperature.[47]

Genentech next argued that the temperature of the supernatant when loaded onto the Protein A column in WO '389 was a missing limitation, and therefore could not anticipate.[48]  The panel majority rejected this argument, noting that a skilled artisan could reasonably understand that the supernatant in WO '389 was also at the disclosed temperature range.[49]

The panel majority also agreed with the Board that the '799 patent was obvious in view of WO '389, since it was known in the art that Protein A leaching was a form of proteolysis that would be affected by temperature.[50]  Adjusting the temperature of the purification was little more than routine optimization due to its ease.[51]  The panel majority also rejected Genentech's secondary indicia of non-obviousness for failure to establish a nexus between the proffered industry praise and the claimed feature of the '799 patent.[52]

In dissent, Judge Newman criticized the panel majority as using hindsight.[53]  Instead, she argued, Genentech had discovered that temperatures in the claimed range resulted in reduced Protein A leaching, which no prior art reference had taught.[54]  Judge Newman noted that the only time WO '389 referenced Protein A leaching was to acknowledge the problem and suggest additional purification steps to separate the leachate from the antibody.[55]  Judge Newman criticized the panel majority and Board for "ignoring the significantly different results in the recited ranges."[56]  Instead, she argued that the range overlap at 18 °C did not anticipate the lower range of the '799 patent.[57]

No Prosecution History Estoppel Based on Rejected IPR Statements: Galderma Labs., L.P. v. Amneal Pharms. LLC, 2020 U.S. App. LEXIS 9341 (Fed. Cir. Mar. 25, 2020)

In Galderma Labs., L.P. v. Amneal Pharms. LLC (non-precedential),[58] the Federal Circuit affirmed a finding of infringement under the doctrine of equivalents and rejected the defendant's plea to bar the doctrine of equivalents based on Patent Owner's statements in an earlier IPR.

At issue in the Hatch-Waxman litigation were two groups of Galderma patents: the Chang Patents and the Ashley II Patents. Both groups relate to low-dose doxycycline formulations to treat acne, rosacea, and other diseases.  On appeal, the panel affirmed the district court's infringement finding as to the Chang Patents, as discussed below.  The panel reversed the doctrine of equivalents infringement finding as to the Ashley II Patents for lack of particularized testimony.

The Chang Patents cover "[a]n oral pharmaceutical composition of doxycycline … the composition consisting of (i) an immediate release portion … (ii) a delayed release (DR) portion comprising 10 mg doxycycline."[59]  The specification defined the term "immediate release," but not "delayed release" ("DR").

Years before the Hatch-Waxman litigation, Amneal petitioned the PTAB for inter partes review of the Chang '740 Patent.  During the IPR, the Patent Owner[60] sought to distinguish the claimed DR portion from the prior art, which recited a "secondary loading portion of slow release pellets that begin dissolving in the stomach."[61]  Patent Owner sought a narrower DR construction by arguing there would be no substantial release of the DR portion in the stomach.[62]  The Board rejected the Patent Owner's proposed construction because it relied on a portion of the specification about enteric coated pellets, and not a delayed release component."[63]  Ultimately, the Board found the prior art did not teach the DR portion under the proper construction.

In the subsequent ANDA litigation, the district court adopted the Board's DR construction and found Amneal's proposed generic infringed the asserted claims because it contained the equivalent of the claimed 10 mg DR portion.

On appeal, Amneal argued Galderma should have been precluded from asserting infringement under the doctrine of equivalents because the Patent Owner's statements during the IPR "clearly and unmistakably surrendered subject matter."[64]  The panel (Lourie, Moore, and Stoll) reiterated that statements made by a patent owner during an IPR proceeding can support disclaimer, but not where the statements were "clearly and expressly rejected by the Patent Office."[65]  Here, there was "no doubt that the Board rejected the Patent Owner's attempt to limit the meaning of delayed release," so a POSA reviewing the record would understand the arguments would not impact claim scope.[66]  The panel thus agreed with the district court that the doctrine of equivalents was available, and found no error in the infringement determination.

Eligibility for Methods of Preparation:  Illumina, Inc. v. Ariosa Diagnostics, Inc., 952 F.3d 1367 (Fed. Cir. 2020)

We reviewed this decision, finding method claims eligible, here.

Claims Directed to Methods of Treatment Are Patent Eligible: Boehringer Ingelheim Pharms., Inc. v. Mylan Pharms., Inc., 2020 U.S. App. LEXIS 8393 (Fed. Cir. Mar. 16, 2020)

In Boehringer Ingelheim Pharms., Inc. v. Mylan Pharms., Inc. (non-precedential),[67] the Federal Circuit reversed and remanded a district court's finding that method of treatment claims were directed to patent ineligible subject matter and upheld the district court's finding of obviousness.

Boehringer sued Mylan for infringement of U.S. Patent Nos. 8,853,156, 9,173,859, and 8673,927, which are generally directed to the treatment of type 2 diabetes with DPP-IV inhibitors, such as linagliptin.[68]  The '156 patent is directed to such treatment in patients "for whom metformin therapy is not appropriate" because metformin is eliminated by the kidneys and many diabetics also have kidney disease or impairment.[69]  In contrast, linagliptin is excreted by the liver.[70]  The district court held the claims 10-17, 24, and 25 of the '156 patent ineligible under § 101 as directed to the abstract idea of "the act of administering the DPP-IV inhibitor to the targeted population."[71]

The district court also found claims 1, 14, 15, 20, and 21 of the '859 patent and claims 7, 9, 15, 25, and 26 of the '927 patent obvious.[72]  These claims were generally directed to treatment of type 2 diabetes with 2.5 or 5 mg doses of linagliptin.[73]  In light of a prior publication that disclosed doses of linagliptin from 1-100 mg, the district court held the claimed doses were presumed obvious in light of the overlapping range, or alternatively a POSA would arrive at the claimed doses through routine experimentation.[74]

The panel (Dyk, Moore, and Hughes) reversed the finding of ineligibility, holding that under Vanda Pharms. Inc. v. West-Ward Pharms. Int'l Ltd.,[75] the claims were directed to a method of treatment and were therefore patent eligible.[76]  Like the claims found patent eligible in Vanda Pharms., the claims of the '156 patent were directed to "a specific method of treatment for specific patents using a specific compound at a specific dose."[77]  Of note is that the district court's opinion was released in 2016,[78] two years before Vanda Pharms. was decided by the Federal Circuit.  For more on the state of eligibility law, please visit this blog.

The panel upheld the district court's finding of obviousness on routine experimentation grounds.  The district court had not clearly erred by relying on expert testimony stating that a POSA would begin experimenting with safety and efficacy at low doses, as recommended by the FDA.[79]  In addition, linagliptin was known to be very potent, so a POSA would likely have chosen linagliptin among the possible DPP-IV inhibitor compounds.[80]

 

[1] 945 F.3d 1368 (Fed. Cir. 2020)

[2] Id.

[3] Id. at 1373.

[4] 831 F.3d 1350 (Fed. Cir. 2016).

[5] Amgen, 945 F.3d at 1373.

[6] Id. at 1376—77.

[7] Id. at 1376.

[8] Id. at 1377.

[9] Id.

[10] Id.

[11] Id. at 1378.

[12] Id. at 1379.

[13] 946 F.3d 1322 (Fed. Cir. 2020).

[14] Id. at 1326—27.

[15] Id. at 1327.

[16] Id. (citing Alcon Research, Ltd. v. Apotex Inc., 687 F.3d 1362, 1369 (Fed. Cir. 2012)).

[17] Id. at 1330.

[18] Id.

[19] Hospira, Inc. v. Amneal Pharm. LLC, 285 F. Supp. 3d. 776, 800 (D. Del. 2018), aff'd, 748 F. App'x 1024 (Fed. Cir. 2019).

[20] 2020 U.S. App. LEXIS 2811 (Fed. Cir. Jan. 29, 2020).

[21] Id. at *1.

[22] Id. at *5.

[23] Teva launched its product one week after the district court entered judgment, and Galderma successfully obtained emergency relief from the district court enjoining Teva's marketing by raising a substantial issue with the anticipation finding.  Id. at *7.  The Federal Circuit, however, stayed the district court's injunction.  Id.

[24] Id. at *11.

[25] Id. at *10.

[26] Id.

[27] 246 F.3d 1368 (Fed. Cir. 2001).

[28] 2020 U.S. App. LEXIS 2811, at *11.

[29] Id.

[30] Id. at *19.

[31] Id. at *13

[32] Id. at *14.

[33] Id.

[34] The panel did not address Teva's obviousness defense and dismissed Teva's cross-appeal as moot.

[35] 946 F.3d 1333, 1340 (Fed. Cir. 2020).

[36] Id. at 1340.

[37] Id. at 1336.

[38] Id.

[39] See id. at 1336.

[40] Id. at 1337.

[41] Hospira, Inc. v. Genentech, Inc., IPR2016-01837, 2019 Pat. App. LEXIS 4308 at *29–32 (P.T.A.B. March 6, 2018).

[42] 2019 Pat. App. LEXIS 4308, at *35; see Titanium Metals Corp. v. Banner, 778 F.2d 775, 782 (Fed. Cir. 1985).

[43] Id. at *36.

[44] Id.

[45] Id.

[46] Id. at 1339.

[47] Id. at 1340.

[48] Genentech attempted to raise this issue as a matter of law, instead of the deferential substantial evidence review of the Board's finding of anticipation.

[49] 946 F.3d at 1340.

[50] Id. at 1341–42.

[51] Id. at 1341.

[52] Id. at 1342 (citing Celgene Corp. v. Peter, 931 F.3d 1342, 1356–63 (Fed. Cir. 2019)).

[53] Id. (Newman, J., dissenting)

[54] Id. at 1344.

[55] Id. at 1346.

[56] Id.

[57] Id. (citing Nidec Motor Corp. v. Zhongshan Board Ocean Motor Corp., 851 F.3d 1270, 1274–75 (Fed. Cir. 2017)).

[58] 2020 U.S. App. LEXIS 9341 (Fed. Cir. Mar. 25, 2020).

[59] Id. at *8.

[60] The Patent Owner during the inter partes review proceedings was Supernus Pharmaceuticals, Inc.  Id. at *3, n. 1.

[61] Id. at *3-4.

[62] Id. at *4.  Specifically, the patent owner aimed to construe DR to include "no substantial release from the portion until some time other than promptly after administration — and in particular, until after the DR portion passes through the acidic stomach and sections of the GI tract below pH 4.5."  Additionally, the Patent Owner sought to distinguish the prior art by stating that the "secondary loading" portion in the prior art was designed to be "leaky in the stomach."

[63] Id.

[64] Id. at *5.  Amneal also argued amendment-based estoppel and claim vitiation, but the panel declined to discuss these issues in its opinion and stated that it did not see error in the district court's decision here.

[65] Id. at *5.

[66] Id. at *7.

[67] 2020 U.S. App. LEXIS 8393 (Fed. Cir. Mar. 16, 2020).

[68] Id. at *2.

[69] Id. at *4.

[70] Id. at *5

[71] Id. at *3.

[72] Id. at *8.

[73] Id. at **9–10.

[74] Id. at *10.

[75] 887 F.3d 1117 (Fed. Cir. 2018).

[76] 2020 U.S. App. LEXIS 8393, at *6.

[77] Id. at *7 (quoting Vanda Pharms., 887 F.3d at 1136).

[78] Boehringer Ingelheim Pharms., Inc. v. HEC Pharm Co., Ltd., Civil Action No. 15-cv-5982 (PGS)(TJB), 2016 U.S. Dist. LEXIS 169812 (D.N.J. Dec. 7, 2016).

[79] Id. at *11.

[80] Id. at **11—12.