`
`United States Court of Appeals
`for the Federal Circuit
`______________________
`
`AMGEN INC., AMGEN MANUFACTURING LTD.,
`Plaintiffs-Appellants
`
`v.
`
`COHERUS BIOSCIENCES INC.,
`Defendant-Appellee
`______________________
`
`2018-1993
`______________________
`
`Appeal from the United States District Court for the
`District of Delaware in No. 1:17-cv-00546-LPS, Chief Judge
`Leonard P. Stark.
`______________________
`
`Decided: July 29, 2019
`______________________
`
`NICHOLAS P. GROOMBRIDGE, Paul, Weiss, Rifkind,
`Wharton & Garrison LLP, New York, NY, argued for plain-
`tiffs-appellants. Also represented by JENNIFER GORDON,
`GOLDA LAI, PETER SANDEL, JACOB WHITT, JENNIFER H. WU;
`LOIS M. KWASIGROCH, KIMBERLIN L. MORLEY, WENDY A.
`WHITEFORD, Amgen Inc., Thousand Oaks, CA.
`
` ADAM G. UNIKOWSKY, Jenner & Block LLP, Washing-
`ton, DC, argued for defendant-appellee. Also represented
`by BRADFORD PETER LYERLA, AARON A. BARLOW, LOUIS
`FOGEL, SUSAN O’BRIEN, Chicago, IL.
` ______________________
`
`

`

`2
`
`AMGEN INC. v. COHERUS BIOSCIENCES INC.
`
`Before REYNA, HUGHES, and STOLL, Circuit Judges.
`STOLL, Circuit Judge.
`
`Amgen Inc. and Amgen Manufacturing Ltd. (collec-
`tively, “Amgen”) sued Coherus BioSciences Inc. for patent
`infringement in the District of Delaware. The district court
`dismissed Amgen’s complaint for failure to state a claim,
`and Amgen appeals. Because prosecution history estoppel
`bars Amgen from succeeding on its infringement claim un-
`der the doctrine of equivalents, we affirm the order of the
`district court.
`
`BACKGROUND
`I
`Recombinant therapeutic proteins are a class of bio-
`logic medicines that are manufactured inside living cells.
`Before a protein can be therapeutically useful, it must first
`be purified from contaminants. Amgen’s U.S Patent
`No. 8,273,707 claims methods of purifying proteins using
`hydrophobic interaction chromatography (“HIC”). A HIC
`column contains a solid, hydrophobic matrix and “is used
`to separate proteins on the basis of hydrophobic interac-
`tions between the hydrophobic moieties of the protein and
`insoluble, immobilized hydrophobic groups on the matrix.”
`’707 patent col. 1 ll. 36–39. In a HIC purification, a buff-
`ered salt solution containing the desired protein and asso-
`ciated impurities is first poured onto a HIC column. Id.
`at col. 1 ll. 40–41. This is known as the “loading” step. The
`salt in the buffer exposes the hydrophobic regions of the
`protein and causes them to adsorb (i.e., attach) onto the hy-
`drophobic groups on the column matrix. See id. at col. 1
`ll. 41–44. The impurities are then washed out of the col-
`umn with a buffered salt solution while the desired protein
`remains attached to the matrix. See id. at col. 4 ll. 27–29.
`Finally, molecules of the desired protein are detached (or
`“eluted”) by pouring a buffer solution with a lower salt con-
`centration through the column. See id. at col. 1 ll. 44–49.
`
`

`

`AMGEN INC. v. COHERUS BIOSCIENCES INC.
`
`3
`
`“Usually, a decreasing salt gradient is used to elute pro-
`teins from a column. As the ionic strength decreases, the
`exposure of the hydrophilic regions of the protein increases
`and proteins elute from the column in order of increasing
`hydrophobicity.” Id. at col. 1 ll. 45–49.
`During the loading step, only a finite amount of protein
`can bind to the matrix. If too much protein is loaded on the
`column, “‘breakthrough’ or loss of protein to the solution
`phase before elution” will occur. Id. at col. 3 ll. 40–41. The
`’707 patent claims a process that reduces breakthrough, or
`in other words, increases the “dynamic capacity” of a HIC
`column. Dynamic capacity refers to “the maximum amount
`of protein in solution which can be loaded onto a column
`without significant breakthrough or leakage of the protein
`into the solution phase of a column before elution.” Id.
`at col. 3 l. 65–col. 4 l. 3.
`Prior art methods of increasing a HIC column’s dy-
`namic capacity included using a higher salt concentration
`in the buffer solution. See id. at col. 3 ll. 37–38. This re-
`sulted in other problems, however, as “high salt can be det-
`rimental to protein stability. High salt increases the
`viscosity of a solution, results in increased formation of ag-
`gregates, results in protein loss due to dilution and filtra-
`tion of the protein after elution from the column, and can
`lead to reduced purity.” Id. at col. 3 ll. 41–45. Instead of
`increasing the concentration of a single salt, the ’707 inven-
`tion:
`provides combinations of salts useful for increasing
`the dynamic capacity of an HIC column compared
`with the dynamic capacity of the column using sep-
`arate salts alone. These combinations of salts al-
`low for a decreased concentration of at least one of
`the salts to achieve a greater dynamic capacity,
`without compromising the quality of the protein
`separation.
`
`

`

`4
`
`AMGEN INC. v. COHERUS BIOSCIENCES INC.
`
`Id. at col. 2 ll. 9–15. All of the ’707 claims require a salt
`combination chosen from one of three pairs: citrate and sul-
`fate, citrate and acetate, or sulfate and acetate. Repre-
`sentative claim 1 recites:
`1. A process for purifying a protein on a hydropho-
`bic 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, respec-
`tively, 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.
`Id. at col. 15 ll. 8–18.
`
`II
` During prosecution, the examiner rejected the then-
`pending ’707 claims as obvious in view of U.S. Patent
`No. 5,231,178 (“Holtz”). J.A. 174–75. The examiner noted
`that Holtz disclosed several salts for improving hydropho-
`bic interactions between a protein and the column matrix.
`J.A. 174. According to the examiner, it would have been
`obvious for a person of ordinary skill to routinely optimize
`Holtz to achieve the claimed invention. J.A. 175.
`On January 26, 2011, Amgen responded to the exam-
`iner’s rejection, pointing out that “the pending claims recite
`a particular combination of salts. No combinations of salts
`
`

`

`AMGEN INC. v. COHERUS BIOSCIENCES INC.
`
`5
`
`[are] taught nor suggested in the Holtz et al. patent, nor
`[are] the particular combinations of salts recited in the
`pending claims taught nor suggested in this reference.”
`J.A. 182. Amgen further noted that the claimed invention
`is directed to increasing dynamic capacity of a HIC column
`and Holtz does not teach dynamic capacity at all. See id.
`It also attached a declaration from ’707 patent inventor
`Anna Senczuk (“Declaration”) for support. The Declaration
`states that the inventors discovered that using a sul-
`fate/citrate or sulfate/acetate salt combination resulted in
`substantial increases in the dynamic capacity of a HIC col-
`umn as compared to using a single salt. See J.A. 187 ¶ 3.
`It further explains that using a sulfate/citrate, sulfate/ace-
`tate, or acetate/citrate combination reduced purification
`costs on a commercial scale as compared to using only a
`single salt. See J.A. 187–88 ¶ 4. The Declaration did not
`discuss any salt pairs other than sulfate/citrate, sulfate/ac-
`etate, and acetate/citrate—the only claimed pairs in the
`’707 patent. Amgen’s response highlighted the particular
`salt pairs disclosed in the Declaration:
`As pointed out in paragraph 4 of the Declaration,
`“The improvement resulting from the use of dual
`salts in HIC goes beyond merely optimizing a col-
`umn to best suit a particular protein. Use of this
`particular combination of salts greatly improves
`the cost-effectiveness of commercial manufacturing
`by reducing the number of cycles required for each
`harvest and reducing the processing time for each
`harvest.”
`J.A. 183 (emphasis added) (quoting J.A. 188 ¶ 4).
`On April 7, 2011, the examiner again rejected the
`claims. The examiner stated that “[a]pplicant contends
`that the instant claims recite a particular combination of
`salts. However, the examiner contends that the cited ref-
`erence does disclose salts used in a method of purification”
`and that adjustment of conditions was within the skill of
`
`

`

`6
`
`AMGEN INC. v. COHERUS BIOSCIENCES INC.
`
`an ordinary artisan. J.A. 949. On August 22, 2011, Amgen
`replied to the examiner’s rejection and reiterated that
`Holtz does not disclose a combination of salts and does not
`disclose enhancing the dynamic capacity of a HIC column.
`See J.A. 160–61. Amgen pointed out that choosing a work-
`ing salt combination was a “lengthy development path” and
`that “merely adding a second salt” would not result in the
`invention. J.A. 162. The examiner then allowed the
`claims.
`
`III
`In August 2016, Coherus filed an abbreviated Biologic
`
`License Application (“aBLA”) seeking FDA approval to
`market a biosimilar version of Amgen’s pegfilgrastim prod-
`uct Neulasta. Pegfilgrastim is a recombinant therapeutic
`protein that stimulates the production of neutrophils, a
`type of white blood cell. The parties exchanged information
`as required by the Biologics Price Competition and Innova-
`tion Act and determined that the ’707 patent should be in-
`cluded in Amgen’s infringement suit. Coherus’s aBLA
`revealed that Coherus’s manufacturing process contains
`several chromatography steps used to purify pegfilgrastim.
`One of the steps involves a chromatography buffer contain-
`ing a salt combination, but not one of the specific combina-
`tions recited in the claims.
`On May 10, 2017, Amgen sued Coherus for infringing
`the ’707 patent based on Coherus’s aBLA. Amgen alleged
`infringement under the doctrine of equivalents because the
`salt combination used in Coherus’s process did not match
`any of the three expressly claimed salt combinations in the
`’707 patent. See J.A. 109–10 ¶ 50. Coherus then moved to
`dismiss Amgen’s complaint under Federal Rule of Civil
`Procedure 12(b)(6).
`The magistrate judge issued a Report and Recommen-
`dation (“Report”), recommending that Coherus’s motion to
`dismiss be granted. Amgen Inc. v. Coherus Biosciences Inc.,
`No. 17-cv-546-LPS-CJB (D. Del. Dec. 7, 2017) (D.I. 50);
`
`

`

`AMGEN INC. v. COHERUS BIOSCIENCES INC.
`
`7
`
`J.A. 12–30. The magistrate judge noted that, during pros-
`ecution, Amgen distinguished Holtz by arguing that Holtz
`did not disclose “one of the particular, recited combinations
`of salts.”1 J.A. 24. Based on this, the magistrate judge de-
`termined that Amgen “clearly and unmistakably—and in-
`deed, repeatedly—indicated
`to competitors
`that
`it
`surrendered processes using combinations of salts different
`from the ‘particular combinations of salts recited in the
`. . . claims[.]’” J.A. 23. The Report concluded that “prose-
`cution history estoppel bars Amgen from now attempting
`to reassert surrendered ground involving other combina-
`tions of salts.” J.A. 28.
`
`The district court adopted the magistrate judge’s Re-
`port and granted Coherus’s motion to dismiss. See Amgen
`Inc. v. Coherus Biosciences Inc., No. 17-cv-546-LPS-CJB,
`2018 WL 1517689, *1 (D. Del. Mar. 26, 2018) (“Decision”).
`It held that “[t]he prosecution history, namely, the pa-
`tentee’s correspondence in response to two office actions
`and a final rejection, shows a clear and unmistakable sur-
`render of claim scope by the patentee.” Id. at *2. The dis-
`trict court further held that, by disclosing but not claiming
`the salt combination used by Coherus, Amgen had dedi-
`cated that particular combination to the public. Id. at *3.
`It concluded that the dedication-disclosure doctrine formed
`an independent basis on which to dismiss Amgen’s in-
`fringement claim. See id. Amgen appeals. We have juris-
`diction under 28 U.S.C. § 1295(a)(1).
`
`
`1 The magistrate judge also noted that, while di-
`rected to a different salt combination, Amgen made the
`same argument—that Holtz did not disclose the claimed
`“particular combination” of salts—during prosecution of
`the parent patent. J.A. 21–22.
`
`

`

`8
`
`AMGEN INC. v. COHERUS BIOSCIENCES INC.
`
`DISCUSSION
`I
` We review an order dismissing a complaint for failure
`to state a claim under the law of the regional circuit, here
`the Third Circuit. McZeal v. Sprint Nextel Corp., 501 F.3d
`1354, 1355–56 (Fed. Cir. 2007). The Third Circuit reviews
`challenges to a dismissal for failure to state a claim de
`novo. Sands v. McCormick, 502 F.3d 263, 267 (3d Cir.
`2007). “In evaluating the propriety of the dismissal, we ac-
`cept all factual allegations as true, construe the complaint
`in the light most favorable to the plaintiff, and determine
`whether, under any reasonable reading of the complaint,
`the plaintiff may be entitled to relief.” Id. at 267–68.
`“Whether prosecution history estoppel applies, and thus
`whether the doctrine of equivalents is available for a par-
`ticular claim limitation, is a question of law reviewed
`de novo.” Spectrum Pharm., Inc. v. Sandoz Inc., 802 F.3d
`1326, 1337 (Fed. Cir. 2015).
`
`II
` We agree with the district court that, during prosecu-
`tion of the ’707 patent, Amgen clearly and unmistakably
`surrendered salt combinations other than the particular
`combinations recited in the claims. Prosecution history es-
`toppel thus bars Amgen from succeeding on its infringe-
`ment claim under the doctrine of equivalents.
`
`“Prosecution history estoppel applies as part of an in-
`fringement analysis to prevent a patentee from using the
`doctrine of equivalents to recapture subject matter surren-
`dered from the literal scope of a claim during prosecution.”
`Trading Techs. Int’l, Inc. v. Open E Cry, LLC, 728 F.3d
`1309, 1322 (Fed. Cir. 2013). Prosecution history estoppel
`can occur in two ways: “either (1) by making a narrowing
`amendment to the claim (‘amendment-based estoppel’) or
`(2) by surrendering claim scope through argument to the
`patent examiner (‘argument-based estoppel’).” Conoco, Inc.
`
`

`

`AMGEN INC. v. COHERUS BIOSCIENCES INC.
`
`9
`
`v. Energy & Envtl. Int’l, L.C., 460 F.3d 1349, 1363
`(Fed. Cir. 2006). To invoke argument-based estoppel, “the
`prosecution history must evince a clear and unmistakable
`surrender of subject matter.” Id. at 1364 (quoting Deering
`Precision Instruments, LLC v. Vector Distribution Sys.,
`Inc., 347 F.3d 1314, 1326 (Fed. Cir. 2003)).
`“[W]here 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.” PODS, Inc. v. Porta
`Stor, Inc., 484 F.3d 1359, 1367 (Fed. Cir. 2007) (internal
`quotation marks omitted) (quoting Southwall Techs., Inc.
`v. Cardinal IG Co., 54 F.3d 1570, 1581–83 (Fed. Cir.
`1995)). “[C]lear assertions made during prosecution in sup-
`port of patentability, whether or not actually required to
`secure allowance of the claim, may also create an estop-
`pel . . . [t]he relevant inquiry is whether a competitor
`would reasonably believe that the applicant had surren-
`dered the relevant subject matter.” Id. at 1368 (internal
`quotation marks omitted).
` We hold that argument-based prosecution history es-
`toppel applies here because Amgen clearly and unmistak-
`ably surrendered unclaimed salt combinations during
`prosecution. In its January 6, 2011 response, Amgen dis-
`tinguished Holtz on the basis that Holtz did not teach or
`suggest the “particular combinations of salts” recited in
`Amgen’s claims. J.A. 182. Indeed, Amgen emphasized
`“particular” and referred to its particular salts three times
`in the span of two pages. See J.A. 182–83. The Declaration
`attached to Amgen’s response also highlights and discusses
`the same particular combinations recited in Amgen’s
`claims. For example, the Declaration refers to sulfate/cit-
`rate and sulfate/acetate as “particular dual salt combina-
`tion[s]” that resulted in increased dynamic capacity as
`compared to a single salt. J.A. 187. It also explains that
`using a sulfate/citrate, sulfate/acetate, or acetate/citrate
`
`

`

`10
`
`AMGEN INC. v. COHERUS BIOSCIENCES INC.
`
`combination (the only claimed combinations) resulted in
`reduced commercial manufacturing costs as compared to
`using only a single salt. See J.A. 187–88. Notably,
`Amgen’s response to the examiner’s office action quotes the
`Declaration’s conclusion that “[u]se of this particular com-
`bination of salts greatly improves the cost-effectiveness of
`commercial manufacturing by reducing the number of cy-
`cles required for each harvest and reducing the processing
`time for each harvest.” J.A. 183 (quoting J.A. 188 ¶ 4).
`Amgen’s response and Declaration do not mention any salt
`combinations other than those claimed.2 Based on
`Amgen’s statements during prosecution, we agree with the
`district court’s conclusion that “a competitor would reason-
`ably believe” that Amgen surrendered unclaimed salt com-
`binations. See PODS, 484 F.3d at 1368.
`Amgen argues that it did not distinguish Holtz on the
`basis that Holtz failed to disclose the particular claimed
`combinations, but rather, it distinguished Holtz on the ba-
`sis that Holtz failed to disclose increasing dynamic capacity
`and failed to disclose any salt combinations at all. See Ap-
`pellant Br. 30–36. According to Amgen, its statement re-
`garding the “particular combinations” of salts “simply
`observes (correctly) as a factual matter that Holtz does not
`disclose using combinations of salts in the first instance,”
`and thus does not clearly and unmistakably surrender un-
`claimed salt pairs. Id. at 35. We disagree.
`In its January 6, 2011 response, 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
`
`2 That Amgen made the same “particular combina-
`tion” argument with respect to the same prior art reference
`as to salts claimed in the parent patent further reflects
`Amgen’s emphasis on the particular claimed combinations.
`See J.A. 1240.
`
`

`

`AMGEN INC. v. COHERUS BIOSCIENCES INC.
`
`11
`
`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.” J.A. 182. So while Amgen did assert
`multiple reasons for why Holtz is distinguishable, our prec-
`edent instructs that estoppel can attach to each argument.
`“[W]here a patent applicant sets forth multiple bases to dis-
`tinguish 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 combi-
`nation of these various grounds.” PODS, 484 F.3d at 1367
`(internal quotation marks omitted) (quoting Southwall
`Techs., 54 F.3d at 1581–83). Amgen did not rely on the
`combination of its asserted grounds to distinguish Holtz, so
`prosecution history estoppel applies to the “particular com-
`binations” ground regardless of the other two arguments
`Amgen made.
`
`Amgen also argues that prosecution history estoppel
`does not apply because its August 22, 2011 response—the
`response after which the claims were ultimately allowed—
`did not contain the argument that Holtz failed to disclose
`the particular claimed salt combinations. See Appellant
`Br. 38–40. According to Amgen, the arguments made in its
`last response prior to allowance “must be the focus of any
`argument-based estoppel analysis.” Id. at 40. Our case
`law does not support this argument. We recognize that
`Amgen did not include the “particular combinations”
`ground in its August 22, 2011 response to the patent office.
`See J.A. 160–62. This does not mean, however, that
`Amgen’s prior statements are erased. There is no require-
`ment that argument-based estoppel apply only to argu-
`ments made in the most recent submission before
`allowance. “[C]lear assertions made during prosecution in
`support of patentability, whether or not actually required
`to secure allowance of the claim, may also create an estop-
`pel[.]” PODS, 484 F.3d at 1368 (quoting Southwall Techs.,
`54 F.3d at 1583). We see nothing in Amgen’s final
`
`

`

`12
`
`AMGEN INC. v. COHERUS BIOSCIENCES INC.
`
`submission that disavows the clear and unmistakable sur-
`render of unclaimed salt combinations made in Amgen’s
`January 6, 2011 response.
`Because we hold that prosecution history estoppel ap-
`plies, we do not reach the issue of whether Amgen dedi-
`cated unclaimed salt combinations to the public.
`CONCLUSION
`We have considered Amgen’s remaining arguments
`and find them unpersuasive. The district court did not err
`in determining that prosecution history estoppel bars
`Amgen from succeeding on its infringement claim under
`the doctrine of equivalents. Accordingly, we affirm the dis-
`trict court’s order dismissing Amgen’s complaint for failure
`to state a claim.
`
`AFFIRMED
`
`