IN THE UNITED STATES DISTRICT COURT
`FOR THE DISTRICT OF DELAWARE
`
`BELCHER PHARMACEUTICALS, LLC
`
`Plaintiff,
`
`V.
`
`HOSPIRA, INC.,
`
`Defendant.
`
`C.A. No. 17-775-LPS
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`Sara E. Bussiere, Stephen B. Brauerman, BAY ARD, P.A. , Wilmington, DE
`
`Cole Y. Carlson, Stefan V. Stein, GRAY ROBINSON, P.A., Tampa, FL
`
`Attorneys for Plaintiff Belcher Pharmaceuticals, LLC
`
`John C. Phillips , Jr., David A. Bilson, Megan C. Haney, PHILLIPS, GOLDMAN,
`MCLAUGHLIN & HALL, P.A., Wilmington, DE
`
`Thomas J. Meloro, Matthew Freimuth, Devon W. Edwards, WILLKIE, FARR & GALLAGHER
`LLP, New York, NY
`
`Attorneys for Defendant Hospira, Inc.
`
`MEMORANDUM OPINION
`
`September 28, 2018
`Wilmington, Delaware
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`Page A
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`ADAMIS EXHIBIT 1019
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`

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`ST krh
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`, U.S. District Judge:
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`This is a patent infringement case arising under the Hatch-Waxman Act. According to
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`the complaint, Plaintiff Belcher Pharmaceuticals, LLC ("Belcher") holds approved New Drug
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`Application ("NDA") No. 205029 for Epinephrine Injection USP, 1 mg/ml, which is prescribed
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`and sold in the United States. (D.I. 1 1 13) Defendant Hospira, Inc. ("Hospira") submitted NDA
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`No. 209359 to the U.S. Food and Drug Administration ("FDA") seeking approval to engage in
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`the commercial manufacture, use, or sale of Epinephrine Injection USP, Abboject™ Syringe
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`lmg/lOmL (the "NDA Product") in the United States. (Id. 18) Belcher sued Hospira, alleging
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`that any future manufacture or sale of Hospira's NDA Product, once it is approved by the FDA,
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`would infringe Belcher's patent, U.S. Patent No. 9,283,197 ('" 197 patent"). 1 (See id. 124) The
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`patent discloses "pharmaceutical formulations of levorotatory-epinephrine, I-epinephrine, more
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`potent and less toxic than existing pharmaceutical formulations of epinephrine, along with
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`methods of producing and using these pharmaceutical formulations of I-epinephrine." ' 197
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`patent, Abstract.
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`Presently before the Court is the parties' dispute over the meaning of certain claim terms
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`in the ' 197 patent. The parties submitted claim construction briefs (see D.I. 69, 70, 79, 80), and
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`expert declarations (see D.I. 71 , 74). The Court held a claim construction hearing on April 11 ,
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`2018, at which both sides presented oral argument and live testimony from their respective
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`experts. (See D.I. 87 ("Tr."); D.I. 85 , 86)
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`1A copy of the ' 197 patent is attached as Exhibit A to the complaint (D.I. 1).
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`I.
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`LEGAL STANDARDS
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`The ultimate question of the proper construction of a patent is a question of law. See
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`Teva Pharm. USA, Inc. v. Sandoz, Inc., 135 S. Ct. 831 , 837 (2015) (citing Markman v. Westview
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`Instruments, Inc., 517 U.S. 370, 388-91 (1996)). "It is a bedrock principle of patent law that the
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`claims of a patent define the invention to which the patentee is entitled the right to exclude."
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`Phillips v. AWH Corp., 415 F.3d 1303, 131 2 (Fed. Cir. 2005) (internal quotation marks omitted).
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`"[T]here is no magic formula or catechism for conducting claim construction." Id. at
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`1324. Instead, the Court is free to attach the appropriate weight to appropriate sources "in light
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`of the statutes and policies that inform patent law." Id.
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`"[T]he words of a claim are generally given their ordinary and customary meaning [ which
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`is] the meaning that the term would have to a person of ordinary skill in the art in question at the
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`time of the invention, i.e., as of the effective filing date of the patent application." Id. at 1312-13
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`(internal citations and quotation marks omitted). "[T]he ordinary meaning of a claim term is its
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`meaning to the ordinary artisan after reading the entire patent." Id. at 1321 (internal quotation
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`marks omitted). The patent specification "is always highly relevant to the claim construction
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`analysis. Usually, it is dispositive; it is the single best guide to the meaning of a disputed term."
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`Vitronics Corp. v. Conceptronic, Inc., 90 F.3d 1576, 1582 (Fed. Cir. 1996).
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`While "the claims themselves provide substantial guidance as to the meaning of particular
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`claim terms," the context of the surrounding words of the claim also must be considered.
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`Phillips, 415 F.3d at 1314. Furthermore, "[o]ther claims of the patent in question, both asserted
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`and unasserted, can also be valuable sources of enlightenment ... [b ]ecause claim terms are
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`normally used consistently throughout the patent." Id. (internal citation omitted).
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`It is likewise true that "[d]ifferences among claims can also be a useful guide .. . . For
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`example, the presence of a dependent claim that adds a particular limitation gives rise to a
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`presumption that the limitation in question is not present in the independent claim." Id. at 1314-
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`15 (internal citation omitted). This "presumption is especially strong when the limitation in
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`dispute is the only meaningful difference between an independent and dependent claim, and one
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`party is urging that the limitation in the dependent claim should be read into the independent
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`claim." SunRace Roots Enter. Co. , Ltd. v. SRAM Corp. , 336 F.3d 1298, 1303 (Fed. Cir. 2003).
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`It is also possible that "the specification may reveal a special definition given to a claim
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`term by the patentee that differs from the meaning it would otherwise possess. In such cases, the
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`inventor' s lexicography governs." Phillips, 415 F.3d at 1316. It bears emphasis that "[e]ven
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`when the specification describes only a single embodiment, the claims of the patent will not be
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`read restrictively unless the patentee has demonstrated a clear intention to limit the claim scope
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`using words or expressions of manifest exclusion or restriction." Hill-Rom Servs. , Inc. v. Stryker
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`Corp., 755 F.3d 1367, 1372 (Fed. Cir. 2014) (quoting Liebel-Flarsheim Co. v. Medrad, Inc., 358
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`F.3d 898, 906 (Fed. Cir. 2004)) (internal quotation marks omitted).
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`In addition to the specification, a court " should also consider the patent's prosecution
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`history, if it is in evidence." Markman v. Westview Instruments, Inc., 52 F.3d 967, 980 (Fed . Cir.
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`1995), ajf'd, 517 U.S. 370 (1996). The prosecution history, which is "intrinsic evidence,"
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`"consists of the complete record of the proceedings before the PTO [Patent and Trademark
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`Office] and includes the prior art cited during the examination of the patent." Phillips, 415 F.3d
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`at 1317. " [T]he prosecution history can often inform the meaning of the claim language by
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`demonstrating how the inventor understood the invention and whether the inventor limited the
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`invention in the course of prosecution, making the claim scope narrower than it would otherwise
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`be." Id.
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`In some cases, "the district court will need to look beyond the patent's intrinsic evidence
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`and to consult extrinsic evidence in order to understand, for example, the background science or
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`the meaning of a term in the relevant art during the relevant time period." Teva, 135 S. Ct. at
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`841. Extrinsic evidence "consists of all evidence external to the patent and prosecution history,
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`including expert and inventor testimony, dictionaries, and learned treatises." Markman, 52 F.3d
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`at 980. For instance, technical dictionaries can assist the court in determining the meaning of a
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`term to those of skill in the relevant art because such dictionaries "endeavor to collect the
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`accepted meanings of terms used in various fields of science and technology." Phillips, 415 F.3d
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`at 1318. In addition, expert testimony can be useful "to ensure that the court's understanding of
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`the technical aspects of the patent is consistent with that of a person of skill in the art, or to
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`establish that a particular term in the patent or the prior art has a particular meaning in the
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`pertinent field." Id. Nonetheless, courts must not lose sight of the fact that "expert reports and
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`testimony [are] generated at the time of and for the purpose of litigation and thus can suffer from
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`bias that is not present in intrinsic evidence." Id. Overall, while extrinsic evidence "may be
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`useful" to the court, it is "less reliable" than intrinsic evidence, and its consideration "is unlikely
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`to result in a reliable interpretation of patent claim scope unless considered in the context of the
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`intrinsic evidence." Id. at 1318-19. Where the intrinsic record unambiguously describes the
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`scope of the patented invention, reliance on any extrinsic evidence is improper. See Pitney
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`Bowes, Inc. v. Hewlett-Packard Co., 182 F.3d 1298, 1308 (Fed. Cir. 1999) (citing Vitronics, 90
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`F.3d at 1583).
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`4
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`Finally, " [t]he construction that stays true to the claim language and most naturally aligns
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`with the patent's description of the invention will be, in the end, the correct construction."
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`Renishaw PLC v. Marposs Societa ' per Azioni, 158 F.3d 1243, 1250 (Fed. Cir. 1998). It follows
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`that "a claim interpretation that would exclude the inventor's device is rarely the correct
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`interpretation." Osram GmbHv. Int'l Trade Comm'n, 505 F.3d 1351 , 1358 (Fed. Cir. 2007)
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`(quoting Modine Mfg. Co. v. US Int '! Trade Comm 'n, 75 F.3d 1545, 1550 (Fed. Cir. 1996)).
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`III. CONSTRUCTION OF DISPUTED TERMS2
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`A.
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`"compounded in an aqueous solution as 1.0 to 1.06 mg/mL I-epinephrine"
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`Plaintiff
`"having 1.0 to 1.06 mg/mL I-epinephrine in an aqueous solution at any point during
`preparation"
`
`Defendant
`See "said injectable liquid formulation compounded", "in an aqueous solution", and "as 1.0 to
`1.06 mg/mL I-epinephrine"
`
`Court
`"having 1.0 to 1.06 mg/mL I-epinephrine in an aqueous solution after the compounding step
`has been completed"
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`The parties dispute whether the claimed concentration range of epinephrine (1.0 to 1.06
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`mg/mL) refers to the concentration range at the end of the compounding step (Defendant's
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`position) or to the concentration range at any time during the compounding step (Plaintiffs
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`position). 3 Plaintiff contends that "the compounding process is a (1) distinct step (2) which takes
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`2 All the disputed claim terms are present in claim 6, the only asserted independent claim. (See
`D.I. 69 at 2)
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`3The parties also dispute the significance of the patent's use of the past tense ("compounded")
`and present tense ("compounding") of the word "compound." (See D.I. 69 at 9-11; D.I. 70 5-6,
`9, 13; D.I. 79 at 2-4; D.I. 80 at 10, 18-20)
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`5
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`time and (3) has varying concentrations of I-epinephrine from start to finish." (D .I. 69 at 6)
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`While Defendant does not the dispute Plaintiffs characterization of the compounding process,4
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`Defendant contends that the claim language refers to "the characteristics of the solution after the
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`compounding step has been completed." (D.I. 70 at 13) (emphasis in original) The Court
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`agrees with Defendant.
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`Plaintiffs main argument is that "claim 6 refers to the varying concentrations of
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`I-epinephrine at various points during the compounding process." (D.I. 79 at 1) But the intrinsic
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`evidence does not support Plaintiffs position. The specification identifies a single concentration
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`of epinephrine during the compounding step. See ' 197 patent at 3 :29-31; 4:61-63 (noting either
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`1.1 mg or 1.03 mg of epinephrine base "per mL" of compounded solution). The prosecution
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`history also describes the compounding step as having a narrow concentration range relative to
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`the concentration in the final product. (See D.I. 63-3 at pp. 2-3 of 6)5 While the Court
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`understands that the compounding step of a drug product may involve many intermediate steps
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`(see D.I. 71 ,r,r 21, 31-36), and potentially the drug product could have different concentrations at
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`different steps of the compounding step, the specification makes no reference to any intermediate
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`steps during compounding, nor does it identify specific epinephrine concentrations during such
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`steps.
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`4Defendant agrees that compounding is a distinct step in the manufacturing process and takes
`time. (D.I. 80 at 3) Defendant also does not dispute the epinephrine concentration could
`potentially change from start to finish during the compounding step. (See D.I. 70 at 17)
`( explaining that "compounding of a drug product can also involve the preparation of intermediate
`solutions")
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`5The Court is persuaded by Defendant' s expert' s opinion that adopting Plaintiffs construction
`would be inconsistent with this portion of the prosecution history. (Se e D.I. 71 at 15 ,r 36)
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`6
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`The Court credits Defendant' s expert's opinion that, for purposes of evaluating the
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`concentration of any particular component in the claimed formulation, a person of ordinary skill
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`in the art ("POSA") would consider only the final concentration at the end of the compounding
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`step after all the relevant components have been added and mixed together, rather than the
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`concentration at any and all times during the compounding step. 6 (See id.) The Court also finds
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`persuasive Defendant's expert's opinion about overages, as described in the patent; the claimed
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`invention makes it possible to prepare an epinephrine formulation with reduced overages, see
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`'197 patent at 4:58-59; 5:4-6, or even with no overage, see id. at 5:23-26. 7 Defendant's expert
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`explains that "an overage can only refer to excess drug product after compounding is complete .
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`. . because there can be no overage until all components are in their final concentrations." (D.I.
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`71 ,, 33, 34) (emphasis in original).
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`Plaintiffs claim differentiation argument does not lead to a different conclusion. Plaintiff
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`contends that"[ c ]laim differentiation shows that the plain language of claims 6 and 7 requires a
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`distinct compounding step." (D.I. 69 at 6-7) Plaintiff contends that claim 6 refers to the
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`concentration during the compounding process, while claim 7 refers to the concentration of the
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`6Plaintiff s expert cites to the specification, which explains that the claimed formulation could be
`made in larger volumes using different sized containers, see 197 patent at 5:8-14, and concludes
`that this means that the formulation could be compounded in many different concentrations, see
`D.I. 74, 28. Plaintiffs expert also summarizes the compounding process of the epinephrine
`formulation according to Defendant's NDA and concludes that the NDA product "will have a
`concentration of 1.0 to 1.06 mg/mL 1-epinephrine at some point during [this] process." (Id. at
`, 30) The Court is not persuaded by Plaintiffs expert' s opinion, which appears to conflate the
`amount of epinephrine ( e.g., 1 mg) with concentration of epinephrine ( e.g., 1 mg/mL ).
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`7These overages correspond to the claim language. Claims 1, 4, and 6, which are drawn to
`formulations compounded as 1.0 to 1.06 mg/mL 1-epinephrine, represent "less or no more than a
`6% overage," while claims 2 and 5, which are drawn to formulations compounded as 1.03
`mg/mL epinephrine, represent "preferably a 3% overage." (D.I. 71 , 33)
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`7
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`final product. (See id. at 7) The Court agrees with Defendant that while these "two
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`concentrations are distinct" (D.I. 80 at 20), they are not distinct in a way that supports Plaintiff.
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`Instead, as Defendant writes: "While dependent claim 7 indeed describes the epinephrine
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`concentration in a final product - a '1 mg per mL, epinephrine" formulation - claim 6 is drawn to
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`the properties of that product as compounded, i.e. , at the end of the compounding step" (id. at 7)
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`(internal citation omitted). Both claims are directed to periods after compounding is complete.
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`Thus, the distinction between claims 6 and 7 supports Defendant's view that, as claimed in the
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`patent, the concentration of import is the concentration after the compou_nding process is
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`complete.
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`The Court has also considered Plaintiffs characterization of its patent as a "pioneer"
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`patent, and its argument that such a patent is entitled to a broad construction, and finds it
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`unavailing in the context of the particular disputes before the Court. 8
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`B.
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`"said injectable liquid pharmaceutical formulation compounded"
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`Plaintiff
`See "compounded in an aqueous solution as 1.0 to 1.06 mg/mL I-epinephrine"
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`Defendant
`"the injectable liquid pharmaceutical formulation formed by combining the active ingredients
`and excipients"
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`Court
`"the injectable liquid pharmaceutical formulation formed by combining the active ingredients
`and excipients"
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`Plaintiff contends that Defendant' s construction would render the term indefinite, as a
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`8Giving the Court' s findings of fact and conclusions oflaw, as expressed in the above analysis, it
`is unnecessary to resolve the parties' disputes as to indefiniteness (see D.I. 69 at 9-10; D.I. 70 at
`18-20) and recapture of disavowed and disclaimed claim scope (D.I. 71 at 16-18).
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`8
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`POSA would not be able to understand the meaning of "the active ingredients and excipients," as
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`they lack proper antecedent basis. (D.I. 69 at 10) Plaintiff further contends that Defendant' s use
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`of the word "formed" is confusing, lacks support in intrinsic evidence, changes the claim's scope,
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`and imposes limitations from dependent claims into independent claims. (Id. at 11) Defendant
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`counters that its construction uses commonly-understood words in the relevant art and is
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`consistent with how a POSA would understand the meaning of the term. (See D.I. 80 at 16, 18)
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`The Court agrees with Defendant.
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`The patent explains that the compounding step involves mixing the components of the
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`formulation in an appropriate solvent. See ' 197 patent, 3: 15-42. The patent also explains that
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`the active pharmaceutical ingredient in the formulation is I-epinephrine; the word excipient is not
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`in the patent. Id. at 3: 15-17. Contrary to Plaintiff s assertions, however, active ingredients and
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`excipients are common words used to generally describe the components of a formulation in the
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`pharmaceutical arts. Even Plaintiffs expert agreed that the compounding step "is the
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`combination of the active ingredients and the excipient[s]." (D.I. 80 Ex. A at 115) He further
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`testified that a POSA would understand the meaning of those words and specifically identified
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`what those are in the asserted patent. (See id. at 94-95) (agreeing that POSA would know what
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`active ingredient and excipient means and identifying, in asserted patent, epinephrine as active
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`ingredient and hydrochloride and sodium chloride as excipients)
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`C.
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`"in an aqueous solution"
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`Plaintiff
`See "compounded in an aqueous solution as 1.0 to 1.06 mg/mL I-epinephrine"
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`Defendant
`"in a homogenous mixture of one or more substances dissolved in a solvent that is mainly
`water"
`
`Court
`"in a homogenous mixture of one or more substances dissolved in a solvent that is mainly
`water"
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`The parties dispute whether this term refers to a solution in which the relevant
`
`components are completely dissolved in the solvent, as Defendant contends (D.I. 70 at 8-11), or
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`to a solution in which the components need not be completely dissolved in the solvent, as
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`Plaintiff contends (D.I. 79 at 7). 9 Plaintiff argues that "there will be an uneven distribution ofl(cid:173)
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`epinephrine particles throughout the mixing tank " under certain circumstances when the
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`components are mixed together at the compounding step. 10 (See D.I. 79 at 7) Defendant argues
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`that its construction is consistent with the customary meaning of the term in the relevant art and
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`with the intrinsic evidence. (D .I. 70 at 8-11) The Court agrees with Defendant.
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`According to the patent, the preparation of the claimed formulation includes "the
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`compounding of the drug substance, followed by initial filtration, filling and sterilization." '197
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`patent at 3:6-9. The patent explains that the "compounding step was performed to place the
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`9There is no dispute that "aqueous" refers to a solution in which solvent primarily consists of
`water. (See id. at 7; see also '197 patent at 3 :20 ("Water for injection was the solvent."))
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`0Plaintiff also argues that Defendant' s construction improperly uses the word "dissolved" in the
`'
`past tense. (D.I. 69 at 11-12; D.I. 79 at 7) But Plaintiff has not persuasively explained, nor is it
`clear to the Court, how the tense of the word is critical to understanding the meaning of the term
`from a POSA's viewpoint.
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`10
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`solid/powder active pharmaceutical ingredient into aqueous solution," and the purpose of
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`filtration is to remove "any particulates, whether bacterial or undissolved ingredients." Id. at
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`3: 17-19; 3 :44-46. While the patent does not provide any definition of an aqueous solution, the
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`Court credits Defendant expert's opinion that a POSA would understand an aqueous solution to
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`be a solution consisting of a homogenous mixture of one or more components in which "the
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`components are uniformly distributed." (D.I. 71126) In the Court's view, the removal of any
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`undissolved ingredients during the filtration step, as described in the patent, is not inconsistent
`
`with Defendant's expert' s opinion.
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`D.
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`"as 1.0 to 1.06 mg/mL I-epinephrine"
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`Plaintiff
`See "compounded in an aqueous solution as 1.0 to 1.06 mg/mL 1-epinephrine"
`
`Defendant
`"the concentration ofl-epinephrine in the compounded solution being within the range of
`1.0 to 1.06 mg/mL"
`
`Court
`"the concentration of 1-epinephrine in the compounded solution being within the range of
`1.0 to 1.06 mg/mL"
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`Plaintiff contends that Defendant's construction lacks antecedent basis, and is thus
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`indefinite, because it is not clear whether "the compounded solution" in claim 6 refers to "the
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`injectable pharmaceutical formulation" or to "a homogenous mixture" under Defendant' s
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`proposed constructions. 11 (D.I. 69 at 12) Defendant responds that in both instances in which
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`"compounded solution" is mentioned in the specification, it refers to the end result of the
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`compounding step. (D.I. 18 at 17) The Court agrees with Defendant.
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`11Plaintiff also argues that Defendant' s construction improperly uses "compounded" in the past
`tense. It is unclear how use of the past tense incorrectly influences the meaning of the term.
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`11
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`The patent explains that "these injectable liquid pharmaceutical formulations of
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`I-epinephrine sterile solution introduced by this invention ... are preferably compounded in an
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`aqueous solution as approximately 1.0 to 1.06 mg/mL I-epinephrine." ' 197 patent, 5:36-41.
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`Additionally, during prosecution, the applicant explained that "the approximately 1.0 to 1.06
`
`mg/mL I-epinephrine describes how the formulation is compounded during manufacturing; a
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`narrow concentration range during the production step of compounding." (D.I. 63-3 at p. 2 of 6)
`
`( emphasis in original) Thus, the intrinsic evidence makes clear that the specified concentration
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`refers to the concentration range of epinephrine during the compounding step. The Court also
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`agrees with Defendant that this concentration range refers to the concentration after the
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`compounding step has been completed, as discussed earlier.
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`E.
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`"and furth er including a tonicity agent"
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`Plaintiff
`No construction is necessary
`
`Defendant
`"the compounded solution including a tonicity agent"
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`Court
`No construction is necessary
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`The dispute is whether a tonicity agent is added to the formulation after the compounding
`
`step has been completed, as Defendant contends (D.I. 70 at 12), or whether it is added during the
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`compounding step, as Plaintiff contends (D.I. 69 at 13). The Court agrees with Plaintiff. The
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`plain meaning of the term is evident to a POSA from reading the specification, which makes
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`clear that the tonicity agent (e.g., sodium chloride) is added during the compounding step. See
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`'197 patent, 3:15-34. Defendant's construction does not add anything meaningful and is
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`unhelpful.
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`IV.
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`CONCLUSION
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`The Court construes the disputed terms as explained above. An appropriate Order
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`follows.
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