By Kevin E. Noonan —

The Federal Circuit again reviewed a determination of infringement under the doctrine of equivalents, in this instance by the International Trade Commission (ITC), again finding that one of the Supreme Court's exceptions to the preclusive effects of prosecution history estoppel (the "tangential relationship" test) applied, and affirmed the ITC's finding of infringement under the doctrine.

Ajinomoto petitioned the International Trade Commission (ITC) under Section 337 (19 U.S.C. § 1337) for an exclusion order against CJ Cheiljedang for importing animal feed-grade L-tryptophan amino acid products produced by several different strains of Escherichia coli and that infringed Ajinomoto's U.S. Patent No. 7,666,655.  The relevant claim of the '655 patent (claim 20) is directed to methods for "producing an aromatic L-amino acid, which comprises cultivating the bacterium according to any one of claims 9–12, 13, 14, 15–18, or 19."  With regard to the claimed bacteria, claims 9 and 15 are relevant to the Commission's (and the Court's) decision:

9.  A recombinant Escherichia coli bacterium, which has the ability to accumulate aromatic L-amino acid in a medium, wherein the aromatic L-amino acid production by said bacterium is enhanced by enhancing activity of a protein in a cell of said bacterium beyond the levels observed in a wild-type of said bacterium,
    [1] and in which said protein consists of the amino acid sequence of SEQ ID NO: 2
    [2] and said protein has the activity to make the bacterium resistant to L-phenylalanine, fluorophenylalanine or 5[-]fluoro-DL-tryptophan,
    [3] wherein the activity of the protein is enhanced by [3a] transformation of the bacterium with a DNA encoding the protein to express the protein in the bacterium, [3b] by replacing the native promoter which precedes the DNA on the chromosome of the bacterium with a more potent promoter, [3c] or by introduction of multiple copies of the DNA encoding said protein into the chromosome of said bacterium to express the protein in said bacterium.

(Boldface numbers were added by the Court in the opinion.)  Claim 15 differs from claim 9 with regard to the protein limitation [1], wherein the protein is limited by nucleotide sequence encoding the amino acid sequence rather claim being limited by the amino acid sequence per se; important to the Court's decision is that claim 15 limits the species of nucleotide sequences to those that hybridize to the sequence corresponding to the amino acid sequence under specified hybridization conditions.

The claimed bacteria have been genetically engineered to increase L-aromatic amino acid production by fermentation, and in particular production of L-tryptophan.  The basis for this increased production depends on an E. coli gene, yddG, that encodes the YddG protein.  This protein is an aromatic amino acid transporter that causes the bacteria to excrete these amino acids into the culture medium.  This is achieved in one of three ways: either by introducing (via plasmid transduction) additional copies of the gene into the bacteria ([3a]); integrating additional copies of this gene into the bacterial chromosome ([3b]); or using a transcriptionally "stronger" promoter to express the endogenous yddG gene ([3c]).

After an investigation, the Commission found that there were three groups of E. coli strains that CJ used to make the imported product:

"[E]arlier strains" [that] contained both the native E. coli yddG gene and the native E. coli yddG promoter, except that the first nucleotide of the promoter was changed through chemical mutagenesis, resulting in a stronger promoter . . . a first "later strain," which contained two copies of a yddG gene: (1) the native E. coli yddG gene with the native E. coli yddG promoter; and (2) a non-E. coli yddG gene with two promoters—(2a) a native non-E. coli yddG promoter and (2b) an rmf promoter . . . [and a second] 'later strain" which also contained two copies of a yddG gene: (1) the native E. coli yddG gene with the native E. coli yddG promoter; and (2) a codon-randomized non-E. coli yddG gene with two promoters—(2a) an rmf promoter and (2b) an rhtB promoter[; the latter two of these strains first having been used after Ajinomoto brought its complaint].

The Administrative Law Judge made a final initial determination where the phrase "re-placing the native promoter . . . with a more potent promoter" was construed to mean "removing the native upstream region of the yddG gene and inserting one of a class of promoters that controls expression of a different gene."  Under this construction, the ALJ held that the claims of the '655 patent were invalid for failure to satisfy the written description requirement of 35 U.S.C. § 112(a) and that the imported products did not infringe the '655 patent claims, either literally or under the doctrine of equivalents.  The full Commission reviewed this decision, affirming the ALJ's claim construction and determination of noninfringement of the imported products made by the earlier strain, and reversing as to the invalidity determination and infringement for products made using the later strains under the doctrine of equivalents.  An exclusion order as to the latter two products ensued and this appeal followed.

The Federal Circuit affirmed the Commission's decision in an opinion by Judge Taranto joined in full by Judge Moore; Judge Dyk concurred in part and dissented in part.  Beginning with the Commission's claim construction, the panel unanimously affirmed that construction and rejected Ajinomoto's argument that the term "encompasses mutagenesis of individual nucleotides within the native promoter" rather than being limited to replacement of the native promoter with a "stronger" one.  The Court found that this construction was supported by the ordinary and customary meaning of the claim language (using as examples of "replacing" an object "a laptop computer, a bicycle, a sail-boat, a blender," comprising an interesting Markush group).  The opinion asserts that "context matters, stating that "[i]n many contexts, one would not refer to swapping out one small component of a larger unit as 'replacing' the unit or as providing a 'substitute' for the unit, even though the net result is a differently constituted larger unit."  This interpretation is consistent with the disclosure in the specification of the '655 patent, which tellingly does not recite the term "replacing" but does recite the word "substituting," (even reciting in an express example that the promoters were substituted), which the Court held was consistent with the Commission's construction of the phrase.  And nothing in the prosecution history was to the contrary.  The opinion recapped the course of prosecution and amendments and argument relevant to the construction, saying that even though patent applicants may have restricted the scope of their claims to a greater extent than necessary, "there is no principle of patent law that the scope of a surrender of subject matter during prosecution is limited to what is absolutely necessary to avoid a prior art reference that was the basis for an examiner's rejection," citing Norian Corp. v. Stryker Corp., 432 F.3d 1356, 1361 (Fed. Cir. 2005), and Biogen Idec, Inc. v. GlaxoSmithKline LLC, 713 F.3d 1090, 1095–96 (Fed. Cir. 2013), for the proposition that this principle applies to rejections under § 112.  Accordingly, the Court affirmed the Commission's construction.

Turning to the Commission's infringement determinations, the panel agreed that imported product made from CJ's earlier strain did not infringe (either literally or under the doctrine of equivalents) but split on whether product made using either of the later strains infringed under the doctrine of equivalents.  With regard to the second of the two later strains, the Commission had found that "the YddG protein encoded by the codon-randomized non-E. coli yddG gene of this strain is an equivalent of SEQ ID NO:2" recited in claim 9.  CJ challenged this ruling on two grounds:  that the amendments made during prosecution raised an estoppel against infringement under the doctrine of equivalents; and that the protein expressed in CJ's second strain failed to satisfy the "structure-way-result" rationale for infringement under the doctrine.  Citing Festo Corp. v. Shoketsu Kinzoku Kogyo Kabushiki Co., 535 U.S. 722, 740 (2002), the majority recognized three exceptions to the scope of prosecution history estoppel, with the second of these (that "the rationale underlying the amendment may bear no more than a tangential relation to the equivalent in question") was dispositive to the issue before the Court.  The basis for the majority's view is that during prosecution, patentees made an amendment to distinguish over prior art the narrowed the scope of the claim from alternatives to the protein having an amino acid sequence identified as SEQ ID NO: 2 that differed by "deletion, substitution, insertion, or addition of several amino acids."  The amendment changed the claim language to recite instead "a protein which comprises an amino acid sequence that is encoded by a nucleotide sequence that hybridizes with the nucleotide sequence of SEQ ID NO:1 under stringent conditions."  The majority considered the circumstances "unusual" because "the original claim provided two alternatives; only the second was modified by amendment; and only the first is asserted as the basis for infringement by CJ's second later strain."  The standard to apply to determine whether the "tangential relationship" test is adequate to rebut the estoppel "focuses on the patentee's objectively apparent reason for the narrowing amendment."  The majority held that Ajinomoto had satisfied this standard:

The objectively evident rationale for the amendment was to limit the set of proteins within the claim's scope so that it no longer included the prior-art E. coli YfiK protein and, more generally, no longer allowed as wide a range of amino acid alterations (hence changes in the protein) as original alternative (B), which had allowed "deletion, substitution, insertion or addition of one or several amino acids in the amino acid sequence shown in SEQ ID NO: 2."  . . .  The reason for the amendment had nothing to do with choosing among several DNA sequences in the redundant genetic code that correspond to the same protein.  Indeed, it is undisputed that the non-E. coli YddG protein produced without codon randomization remains within the literal claim scope even after the amendment and that the non-E. coli YddG protein is identical whether produced from the codon randomized or the noncodon-randomized version of the non-E. coli yddG gene.

Accordingly, the reason for the narrowing amendment — limiting the amino-acid makeup of the proteins included in one of the alternatives covered by the claim — is unrelated to differences among the several DNA sequences that encode a given protein.

Regarding CJ's second ground of appeal, the majority further found that the non-E. coli YddG protein of CJ's second later strain satisfied the "structure-way-result" test for infringement under the doctrine of equivalents compared to the claimed E. coli YddG protein.  This conclusion was supported by expert testimony as to the function of the two proteins (as "'export protein[s] that actively export[] aromatic L-amino acids and aromatic L-amino acid analogs' out of the bacterial cell"), as was the "way" prong of the test (based on the 85-95% identical structure of the two proteins) and the result (that the consequence of the biochemical activity of each protein was for L-tryptophan to accumulate extracellularly).  The majority also rejected CJ's contention that its strains did not become "resistant" to L-tryptophan (i.e., could grow in its absence) based on CJ 's own fermentation evidence.  The majority found no error in any of these conclusions and thus affirmed the Commission's conclusion that product produced by CJ's two later bacterial strains infringed under the doctrine of equivalents.

Finally, the panel unanimously held that asserted claim 20 of the '655 patent was not invalid for failure to satisfy the written description requirement.  The panel found that patentees had disclosed a "representative number" of stronger promoters (four, exactly:  PL promoter of lambda phage, the lac promoter, the trp promoter, and the trc promoter) and the person of ordinary skill would be cognizant of other members of this group from, inter alia, prior art disclosures thereof.  "[T]he genus of more potent promoters was already well explored in the relevant art by the time of the '655 patent's invention.  In these circumstances, the Commission permissibly found in the specification, read in light of the background knowledge in the art, a representative number of species for the genus of more potent promoters," according to the panel.

Judge Dyk's dissent was limited to the application of the tangential relationship exception to preclude prosecution history estoppel from negating infringement under the doctrine of equivalents.  For Judge Dyk, the amendments to the claims of the '655 patent had a direct relationship to the elements at issue (non-E. coli YddG protein of CJ's second later strain) and thus L-tryptophan produced by either of CJ's later two bacterial strains did not infringe under the doctrine of equivalents.

Ajinomoto Co. v. International Trade Commission (Fed. Cir. 2019)
Panel: Circuit Judges Dyk, Moore, and Taranto
Opinion by Circuit Judge Taranto; opinion concurring in part and dissenting in part by Circuit Judge Dyk

By Kevin E. Noonan —

In its decision in a consolidated appeal, Eli Lilly & Co. v. Hospira, Inc. and Eli Lilly & Co. v. Dr. Reddy's Laboratories, Ltd., the Federal Circuit had the occasion to apply the Supreme Court's distinction regarding the limits of prosecution history estoppel on the doctrine of equivalents, regarding the effects on the estoppel of amendments made that are only tangentially related to patentability.  In this case, this doctrine salvaged a decision in favor of the patentee Eli Lilly in both cases, keeping generic versions of Lilly's patented drug from FDA approval until Lilly's Orange Book-listed patent have expired.

The cases arose in ANDA litigation over Lilly's U.S. Patent No. 7,772,209 directed to "improved" methods for administering its anticancer drug Alimta® (pemetrexed disodium), a frequent target for generic drugmakers and the accompanying litigation (the opinion notes in a footnote that "[t]his is the fourth appeal we have decided concerning Alimta® and the third specifically concerning the '209  patent").  The drug itself, an antifolate metabolic inhibitor of thymidylate synthase, inhibits cell growth (normal and malignant) by interfering with production of DNA precursors and hence inhibiting replication.  The anticancer efficacy for this drug (like many anticancer drugs) relies on the greater replicative activity of cancer cells compared with normal cells.

Pemetrexed, and its disodium salt, is not a new drug, being disclosed and claimed in U.S. Patent No. 5,344,932, and Lilly's licensed U.S. Patent No. 4,997,838, that disclosed a large genus of structurally related compounds that encompass pemetrexed but did not disclose the molecule.  This reference also taught that "pharmaceutically acceptable bases," such as "alkali metals, alkali earth metals, non-toxic metals, ammonium, and substituted ammonium" could be prepared from the disclosed antifolate inhibitors.

Lilly's own investigations showed that Alimta® administration is nevertheless associated with significant side-effects, including "severe hematologic and immunologic side effects, resulting in infections, nausea, rashes, and even some deaths," which are not uncommon with antifolates according to the '209 patent specification.  The '209 patent claims methods for pemetrexed administration supplemented with folic acid and a methylmalonic acid-lowering agent (including, e.g.,vitamin B12), "improved" to the extent that these side effects are reduced.  Claim 12 is representative:

12.  An improved method for administering pemetrexed disodium to a patient in need of chemotherapeutic treatment, wherein the improvement comprises:
    a) administration of between about 350 μg and about 1000 μg of folic acid prior to the first administration of pemetrexed disodium;
    b) administration of about 500 μg to about 1500 μg of vitamin B12, prior to the first administration of pemetrexed disodium; and
    c) administration of pemetrexed disodium.

In a parent application to the '209 patent, broader claims directed to methods for reducing antifolate toxicity recited administration of a broad class of antifolates with methylmalonic acid lowering agents with or without folic acid.  These claims were rejected as being anticipated by an earlier prior art reference or for being obvious over a combination of references.  In response, Lilly amended the rejected claims to pemetrexed disodium and argued that the asserted art either did not recite the pemetrexed disodium or, for overcoming the obviousness rejection, that the art did not suggest vitamin supplementation.

The defendants in ANDA litigation did not request FDA approval for pemetrexed disodium but for a different salt — the ditromethamine salt -– and argued to the agency that "their choice of the tromethamine cation was immaterial because pemetrexed dissociates from its counterion in solution" and that this salt was known to be safe for pharmaceutical use.  At trial against Dr. Reddy's Laboratories, the District Court construed the term "administration of pemetrexed disodium" to mean "liquid administration of pemetrexed disodium," which "is accomplished by dissolving the solid compound pemetrexed disodium into solution."  Using this construction, the District Court denied defendant's motion for summary judgment of noninfringement on the ground that Lilly was not precluded by prosecution history estoppel to assert that Dr. Reddy's ditromethamine pemetrexed salt was an equivalent to Lilly's claimed disodium salt.  The Court reasoned that the amendment made during the earlier prosecution was only tangentially related to the differences in these salts, the amendment being made to distinguish different antifolate species and not different salt forms thereof.  The Court also rejected defendant's "dedication to the public" argument with regard to the earlier known antifolate compounds disclosed in the '838 patent because that patent disclosed a large genus comprising thousands of compounds.

In litigation with Hospira, Eli Lilly argued both literal infringement as well as infringement under the doctrine of equivalents, based on Hospira's label that permitted pemetrexed ditromethamine to be reconstituted in saline.  Hospira conceded (subject to appeal) that its product would infringe, and the District Court granted summary judgment against Hospira on both literal infringement and infringement under the doctrine of equivalents.

The Federal Circuit reversed-in-part and affirmed-in-part, in an opinion by Judge Lourie joined by Judges Moore and Taranto.  Regarding literal infringement, the Court held that:

It was clearly erroneous for the district court to hold that the "administration of pemetrexed disodium" step was met because Hospira's pemetrexed ditromethamine product will be dissolved in saline before administration.  A solution of pemetrexed and chloride anions and tromethamine and sodium cations cannot be deemed pemetrexed disodium simply because some assortment of the ions in the solution consists of pemetrexed and two sodium cations.  As Lilly acknowledges throughout its brief, pemetrexed disodium is a salt.  . . .  Once diluted, the salt's crystalline structure dissolves, and the individual ions dissociate.  . . .  In other words, pemetrexed disodium no longer exists once dissolved in solution, and, as a corollary, a different salt of pemetrexed dissolved in saline is not pemetrexed disodium [citations to the record omitted].

Because Hospira did not administer pemetrexed disodium, the panel reversed the District Court's finding of literal infringement.

Turning to the doctrine of equivalents, the opinion immediately cites Festo Corp. v. Shoketsu Kinzoku Kogyo Kabushki Co., 535 U.S. 722, 733 (2002), in support of the principle that "[f]ew propositions of patent law have been so consistently sustained by the Supreme Court as the doctrine of equivalents."  Having evinced the due measure of obeisance to the Court's jurisprudence, the panel then notes (somewhat in its own defense) that "the Supreme Court has also acknowledged that the doctrine of equivalents, 'when applied broadly, conflicts with the definitional and public-notice functions of the statutory claiming requirement,'" citing Warner-Jenkinson Co. v. Hilton Davis Chem. Co., 520 U.S. 17, 40 (1997), and that Federal Circuit law "emphasized . . . that the doctrine of equivalents is 'the exception, however, not the rule,' and not merely 'the second prong of every infringement charge, regularly available to extend protection beyond the scope of the claims,'" citing London v. Carson Pirie Scott & Co., 946 F.2d 1534, 1538 (Fed. Cir. 1991).  In particular, countervailing doctrines that properly cabin the doctrine of equivalents are those of prosecution history estoppel and dedication of disclosed but not claimed embodiments to the public.

With regard to prosecution history estoppel, under Festo the question is whether the amendments made in the earlier patent from which the '209 patent claims priority were made for reasons related to patentability and do not fall within Supreme Court-recognized exceptions.  As set forth on the opinion, Lilly did not dispute that its amendments satisfied the fundamental requirements of behavior that raises the estoppel:  that "the amendment in question was both narrowing and made for a substantial reason relating to patentability."  Nevertheless, Lilly relied on the exception that the rationale for its amendments "[bore] no more than a tangential relation to the equivalent in question," citing Festo.  Hospira and Dr. Reddy's Laboratories colorfully argued that "the tangential exception is not a patentee's-buyer's-remorse exception" and that the tangential relationship exception should be construed narrowly.  The Federal Circuit held that appellants had advanced a "too rigid" application of prosecution history estoppel.  The Court agreed with the District Court's assessment that Lilly had narrowed the claims of the earlier, related application to overcome rejection based on treatment with methotrexate, and that "the particular type of salt to which pemetrexed is complexed relates only tenuously to the reason for the narrowing amendment," which was to avoid prior art directed to methotrexate administration.

Regarding prosecution of the '209 patent, the panel found no basis for Hospira's argument that claims were amended to recite pemetrexed disodium to avoid prior art asserted during that prosecution.  Reiterating the "remorse" theme, Dr. Reddy's Laboratories "insists" that Federal Circuit case law has established that "an applicant's remorse at ceding more claim scope than necessary is not a reason for the tangential exception to apply, citing Lucent Techs., Inc. v. Gateway, Inc., 525 F.3d 1200, 1218 (Fed. Cir. 2008), and Schwarz Pharma, Inc. v. Paddock Labs., Inc., 504 F.3d 1371, 1377 (Fed. Cir. 2007).  The panel countered that the exception itself "only exists because applicants over-narrow their claims during prosecution" and that "the reason for an amendment, where the tangential exception is invoked, cannot be determined without reference to the context in which it was made, including the prior art that might have given rise to the amendment in the first place."  According to the panel, "[w]e do not demand perfection from patent prosecutors, and neither does the Supreme Court (citing Festo).  Lilly's burden was to show that pemetrexed ditromethamine was 'peripheral, or not directly relevant, to its amendment . . . [a]nd as we concluded above, Lilly has done so."  Finally, the panel refused to adopt Dr. Reddy's position as a bright-line rule, stating that "such a bright-line rule is both contrary to the equitable nature of prosecution history estoppel, [citing Festo], and inconsistent with the equitable spirit that animates the doctrine of equivalents, citing Graver Tank & Mfg. Co. v. Linde Air Prods. Co., 339 U.S. 605, 608 (1950).

While the question of "whether prosecution history estoppel applies to bar a doctrine of equivalents claim is a question of law, . . . citing Regents of Univ. of Cal. v. Dakocytomation Cal., Inc., 517 F.3d 1364, 1371 (Fed. Cir. 2008) (citing Pharmacia & Upjohn Co. v. Mylan Pharm., Inc., 170 F.3d 1373, 1376 (Fed. Cir. 1999)," the decision in this case depends critically on the facts surrounding the amendments and the reasons for them.  In a footnote, the opinion states that:

[I]n applying the Supreme Court's framework, we find the analogies to other cases less helpful than a direct consideration of the specific record of this case and what it shows about the reason for amendment and the relation of that reason to the asserted equivalent.  This case-specific focus, within the governing framework, comports with the equitable nature of prosecution history estoppel.

The panel completes its analysis by rejecting Dr. Reddy's Laboratories' argument that the "disclosure-dedication" rule, Johnson & Johnston Assocs. Inc. v. R.E. Serv. Co., 285 F.3d 1046, 1054 (Fed. Cir. 2002) (en banc), prevented Lilly from asserting its claims under the doctrine of equivalents.  The Federal Circuit agreed with Lilly that this doctrine does not apply where, as here, the patent does not disclose the specific embodiment at issue (here, pemetrexed ditromethamine) and thus could not have dedicated it to the public.  Despite reference to earlier disclosure comprising about 50 antifolate compounds (none of them pemetrexed) and disclosure related to pharmaceutically acceptable salts thereof (but not ditromethamine), in the absence of express disclosure of pemetrexed ditromethamine "we see no reason why a skilled artisan would set out on DRL's winding path to cobble together pemetrexed ditromethamine" and thus held that the dedication-disclaimer rule did not preclude Lilly from asserting infringement under the doctrine of equivalents.

And on the merits, the Federal Circuit found no clear error in the District Court's determination that the methods for treating pemetrexed ditromethamine claimed by defendants was equivalent to Lilly's claimed methods for administering pemetrexed disodium.  Thus, the Federal Circuit affirmed the District Court's grant in each case of summary judgment of infringement under the doctrine of equivalents.

Eli Lilly & Co. v. Hospira, Inc. (Fed. Cir. 2019)
Panel: Circuit Judges Lourie, Moore, and Taranto
Opinion by Circuit Judge Lourie

By Donald Zuhn —

Last month, in Amgen Inc. v. Coherus BioSciences Inc., the Federal Circuit affirmed a decision by the U.S. District Court for the District of Delaware dismissing a complaint filed by Amgen Inc. and Amgen Manufacturing Ltd. against Coherus BioSciences Inc. for failure to state a claim.  Amgen had filed suit against Coherus for infringement of U.S. Patent No. 8,273,707.

The '707 patent is directed to methods of purifying proteins using hydrophobic interaction chromatography ("HIC"), in which a solid, hydrophobic matrix is used to separate proteins on the basis of hydrophobic interactions between the hydrophobic moieties of the protein and insoluble, immobilized hydrophobic groups on the matrix.  The process disclosed in the '707 patent increases an HIC column's dynamic capacity, which is the maximum amount of protein in a solution which can be loaded onto a column without significant leakage (or breakthrough) of the protein into the solution phase before elution.  Prior art HIC columns used buffers with higher salt concentrations to increase dynamic capacity, but such methods also resulted in protein instability, increased viscosity of a solution, increased formation of aggregates, protein loss due to dilution and filtration of the protein after elution from the column, and reduced protein purity.  According to the '707 patent, the claimed process "provides combinations of salts useful for increasing the dynamic capacity of an HIC column compared with the dynamic capacity of the column using separate salts alone."  Representative claim 1 recites:

1.  A process for purifying a protein on a hydrophobic interaction chromatography column such that the dynamic capacity of the column is increased for the protein comprising
    mixing a preparation containing the protein with a combination of a first salt and a second salt,
    loading the mixture onto a hydrophobic inter-action chromatography column, and eluting the protein,
    wherein the first and second salts are selected from the group consisting of citrate and sulfate, cit-rate and acetate, and sulfate and acetate, respectively, and
    wherein the concentration of each of the first salt and the second salt in the mixture is between about 0.1 M and about 1.0.

During prosecution of the application that issued as the '707 patent, the Examiner rejected the claims as obvious in view of U.S. Patent No. 5,231,178 ("Holtz").  Amgen responded to the rejection by arguing that Holtz neither taught nor suggested using combinations of salts nor the particular salts recited in the claims.  Amgen also noted that the claimed invention was directed to increasing the dynamic capacity of an HIC column, and that Holtz did not teach dynamic capacity.  In addition, Amgen provided a declaration from one of the inventors stating that using a sulfate/citrate or sulfate/acetate salt combination resulted in substantial increases in the dynamic capacity of a HIC column as compared to using a single salt.  After the Examiner again rejected the claims, Amgen reiterated that Holtz does not disclose a combination of salts and does not disclose enhancing the dynamic capacity of an HIC column, and also pointed out that "merely adding a second salt" would not result in the invention.  The Examiner thereafter allowed the claims.

In 2016, Coherus filed an abbreviated Biologic License Application ("aBLA") seeking FDA approval to market a biosimilar version of Amgen's pegfilgrastim product Neulasta.  After exchanging information pursuant to the Biologics Price Competition and Innovation Act ("BPCIA"), the parties determined that the '707 patent should be included in Amgen's infringement suit against Coherus.  In particular, the aBLA filed by Coherus indicates that its pegfilgrastim manufacturing process utilizes several chromatography steps, one of which involves a chromatography buffer containing a salt combination, albeit not one of the combinations specifically recited in the claims.

Based on Coherus' aBLA, Amgen filed suit against Coherus alleging infringement of the '707 patent under the doctrine of equivalents.  Coherus responded by moving to dismiss Amgen's complaint under Fed. R. Civ. P. 12(b)(6).  Noting that Amgen had distinguished Holtz by arguing that the reference did not disclose "one of the particular, recited combinations of salts," a magistrate judge recommended that Coherus' motion be granted because "prosecution history estoppel bars Amgen from now attempting to reassert surrendered ground involving other combinations of salts."  The District Court adopted the magistrate judge's recommendation and granted Coherus' motion to dismiss.  Amgen appealed the dismissal to the Federal Circuit.

In affirming the District Court's dismissal of Amgen's complaint, the Federal Circuit found that "during prosecution of the '707 patent, Amgen clearly and unmistakably surrendered salt combinations other than the particular combinations recited in the claims," and determined that "[p]rosecution history estoppel thus bars Amgen from succeeding on its infringement claim under the doctrine of equivalents."  Amgen, however, argued that during prosecution it had distinguished Holtz on the basis that this reference failed to disclose increasing dynamic capacity and failed to disclose any salt combinations at all.  The Federal Circuit noted that:

Amgen asserted three bases for distinguishing Holtz: (1) "[n]o combinations of salts [are] taught nor suggested in the Holtz et al. patent"; (2) "nor [are] the particular combinations of salts recited in the pending claims taught nor suggested in [Holtz],"; and (3) "[t]here is no description or suggestion in Holtz et al. for the use of any combination of salts to increase the dynamic capacity of a HIC."

Citing PODS, Inc. v. Porta Stor, Inc., 484 F.3d 1359, 1367 (Fed. Cir. 2007), the Federal Circuit also noted that "where a patent applicant sets forth multiple bases to distinguish between its invention and the cited prior art, the separate arguments [can] create separate estoppels as long as the prior art was not distinguished based on the combination of these various grounds."  The Court concluded that "Amgen did not rely on the combination of its asserted grounds to distinguish Holtz," and that "while Amgen did assert multiple reasons for why Holtz is distinguishable, our precedent instructs that estoppel can attach to each argument."  The Court therefore determined that in the instant case, "prosecution history estoppel applies to the 'particular combinations' ground regardless of the other two arguments Amgen made."

Amgen also argued that prosecution history should not apply in the instant case because the response filed prior to allowance of the claims did not contain the argument that Holtz failed to disclose the particular claimed salt combinations.  Explaining that "[t]here is no requirement that argument-based estoppel apply only to arguments made in the most recent submission before allowance," the Federal Circuit stated that "[w]e see nothing in Amgen's final submission that disavows the clear and unmistakable surrender of unclaimed salt combinations made in Amgen's [earlier] response."  The Federal Circuit therefore determined that the District Court did not err in determining that prosecution history estoppel barred Amgen from succeeding on its infringement claim under the doctrine of equivalents, and affirmed the District Court's order dismissing Amgen's complaint for failure to state a claim.

Amgen Inc. v. Coherus BioSciences Inc. (Fed. Cir. 2019)
Panel: Circuit Judges Reyna, Hughes, and Stoll
Opinion by Circuit Judge Stoll