Trials@uspto.gov
`571-272-7822
`
`
` Paper No. 11
`
` Entered: January 8, 2016
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`PHARMACOSMOS A/S,
`Petitioner,
`
`v.
`
`LUITPOLD PHARMACEUTICALS, INC.,
`Patent Owner.
`____________
`
`Case IPR2015-01493
`Patent 8,431,549 B2
`____________
`
`
`Before TONI R. SCHEINER, LORA M. GREEN, and
`CHRISTOPHER G. PAULRAJ, Administrative Patent Judges.
`
`PAULRAJ, Administrative Patent Judge.
`
`
`
`DECISION
`Institution of Inter Partes Review
`37 C.F.R. § 42.108
`
`
`
`
`
`
`PGR2020-00009
`Pharmacosmos A/S v. American Regent, Inc.
`Petitioner Ex. 1096 - Page 1
`
`
`571-272-7822
`
`
` Paper No. 11
`
` Entered: January 8, 2016
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`PHARMACOSMOS A/S,
`Petitioner,
`
`v.
`
`LUITPOLD PHARMACEUTICALS, INC.,
`Patent Owner.
`____________
`
`Case IPR2015-01493
`Patent 8,431,549 B2
`____________
`
`
`Before TONI R. SCHEINER, LORA M. GREEN, and
`CHRISTOPHER G. PAULRAJ, Administrative Patent Judges.
`
`PAULRAJ, Administrative Patent Judge.
`
`
`
`DECISION
`Institution of Inter Partes Review
`37 C.F.R. § 42.108
`
`
`
`
`
`
`PGR2020-00009
`Pharmacosmos A/S v. American Regent, Inc.
`Petitioner Ex. 1096 - Page 1
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`IPR2015-01493
`Patent 8,431,549 B2
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`I.
`
`INTRODUCTION
`
`Pharmacosmos A/S (“Petitioner”) filed a Petition (Paper 1, “Pet.”),
`requesting institution of an inter partes review of claims 1–10, 12–17, 19,
`and 21 of U.S. Patent No. 8,431,549 B2 (Ex. 1001, “the ’549 patent”).
`Luitpold Pharmaceuticals, Inc. (“Patent Owner”) timely filed a Preliminary
`Response (Paper 7, “Prelim. Resp.”). We have jurisdiction under
`35 U.S.C. § 314, which provides that an inter partes review may not be
`instituted “unless . . . there is a reasonable likelihood that the petitioner
`would prevail with respect to at least 1 of the claims challenged in the
`petition.”
`Upon consideration of the Petition and the Preliminary Response, and
`for the reasons explained below, we determine that Petitioner has shown that
`there is a reasonable likelihood that it would prevail with respect to at least
`one of the challenged claims. We thus institute an inter partes review of
`claims 1–5, 9, 12–14, 16, and 19 of the ’549 patent.
`
`A. Related Proceedings
`The parties do not identify any pending judicial or administrative
`matters that would affect, or be affected by, a decision in this proceeding.
`Pet 1; Paper 6, 2. Petitioner, however, has sought inter partes review for
`related patents in the following proceedings: Case IPR2015-01490 (U.S.
`Patent No. 7,754,702 B2) and Case IPR2015-01495 (U.S. Patent No.
`8,895,612 B2).
`
`B. The ’549 Patent (Ex. 1001)
`The ’549 patent generally relates to the treatment of iron-related
`conditions with iron carbohydrate complexes. Ex. 1001, Abstract; 1:16–17.
`
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`According to the specification, parenteral iron therapy is known to be
`effective in a variety of diseases and conditions including, inter alia, severe
`iron deficiency and iron deficiency anemia. Id. at 1:21–29. However, iron
`dextran, the first parental product available in the United States, has been
`associated with an incidence of anaphylactoid-type reactions. Id. at 1:47–50.
`The specification further notes that pharmacokinetic studies suggested that
`doses of iron complexes containing higher than 200 mg of iron are generally
`unsuitable, and that the conventional therapy model prescribes repeated
`applications of lower doses over several days. Id. at 2:9–12.
`The specification describes the administration of iron carbohydrate
`complexes at a relatively high single unit dosage, i.e., containing at least 0.6
`grams of elemental iron, “thereby providing a safe and efficient means for
`delivery of a total dose of iron in fewer sessions over the course of
`therapeutic treatment.” Id. at 2:23–37. According to the specification, the
`inventors discovered that certain characteristics of iron carbohydrate
`complexes make them amenable to administration at dosages far higher than
`contemplated by current administration protocols. Id. at 10:55–58. Among
`these preferable characteristics are: a nearly neutral pH (e.g., about 5 to
`about 7); physiological osmolarity; stable carbohydrate component; an iron
`core size no greater than about 9 nm; mean diameter particle size no greater
`than about 35 nm, preferably about 25 nm to about 30 nm; slow and
`competitive delivery of the complexed iron to endogenous iron binding sites;
`serum half-life of over about 7 hours; low toxicity; non-immunogenic
`carbohydrate component; no cross reactivity with anti-dextran antibodies;
`and/or low risk of anaphylactoid/hypersensitivity reactions. Id. at 10:60–
`11:2.
`
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`
`C. Illustrative Claims
`Petitioner challenges claims 1–10, 12–17, 19, and 21 of the ’549
`patent. Independent claim 1 is illustrative, and is reproduced below:
`1. A method of treating a disease, disorder, or condition
`characterized by iron deficiency or dysfunctional iron
`metabolism resulting in reduced bioavailability of dietary
`iron, comprising administering to a subject in need thereof
`an iron carbohydrate complex in a single dosage unit of at
`least about 0.6 grams of elemental iron,
`wherein,
`the iron carbohydrate complex is selected from the
`group consisting of an iron mannitol complex, and an
`iron polyisomaltose complex, an iron polymaltose
`complex, an iron gluconate complex, and an iron sorbitol
`complex,
`the iron carbohydrate complex has a substantially
`non-immunogenic carbohydrate component, and
`the disease, disorder or condition is not Restless Leg
`Syndrome.
`
`D. The Asserted Grounds of Unpatentability
`Petitioner challenges the patentability of the claims of the ’549 patent
`on the following grounds (Pet. 4):
`References
`Vance1
`
`Claims challenged
`1, 7, 8, 15, 17, and 21
`
`Basis
`§ 102(b)
`
`van Zyl-Smit2
`
`§ 102(b)
`
`2–5, 9, 16, and 19
`
`
`1 Vance et al., US 5,541,158, issued July 30, 1996 (Ex. 1002) (hereinafter
`“Vance”).
`2 Roal van Zyl-Smit & Janet A. Halkett, Experience with the Use of an Iron
`Polymaltose (Dextrin) Complex Given by Single Total Dose Infusion to
`Stable Chronic Haemodialysis Patients, 92 NEPHRON (2002) (Ex. 1004)
`(hereinafter “van Zyl-Smit”).
`
`
`
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`
`References
`Groman3
`
`van Zyl-Smit and Groman
`
`
`II. ANALYSIS
`
`A. Claim Construction
`
`Basis
`§ 102(b)
`
`§ 103(a)
`
`Claims challenged
`10 and 12–14
`
`10
`
`We interpret claims using the “broadest reasonable construction in
`light of the specification of the patent in which [they] appear[].” 37 C.F.R.
`§ 42.100(b); see also In re Cuozzo Speed Techs., LLC, 793 F.3d 1268, 1278–
`79 (Fed. Cir. 2015) (“Congress implicitly approved the broadest reasonable
`interpretation standard in enacting the AIA,” 4 and “the standard was
`properly adopted by PTO regulation.”). Under the broadest reasonable
`construction standard, claim terms are given their ordinary and customary
`meaning, as would be understood by one of ordinary skill in the art at the
`time of the invention. In re Translogic Tech., Inc., 504 F.3d 1249, 1257
`(Fed. Cir. 2007). “Absent claim language carrying a narrow meaning, the
`PTO should only limit the claim based on the specification . . . when [it]
`expressly disclaim[s] the broader definition.” In re Bigio, 381 F.3d 1320,
`1325 (Fed Cir. 2004). “Although an inventor is indeed free to define the
`specific terms used to describe his or her invention, this must be done with
`reasonable clarity, deliberateness, and precision.” In re Paulsen, 30 F.3d
`1475, 1480 (Fed. Cir. 1994).
`
`3 Groman et al., US 2003/0232084 A1, published Dec. 18, 2003 (Ex. 1003)
`(hereinafter “Groman”).
`4 The Leahy-Smith America Invents Act, Pub. L. No. 112−29, 125 Stat. 284
`(2011) (“AIA”).
`
`
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`
`1. “substantially non-immunogenic carbohydrate component”
`The challenged claims require that “the iron carbohydrate complex
`has a substantially non-immunogenic carbohydrate component.” Petitioner
`argues that the broadest reasonable interpretation of “substantially non-
`immunogenic carbohydrate component” is a carbohydrate component
`resulting in a “low risk of anaphylactoid/hypersensitivity reactions.” Pet. 20
`(citing Ex. 1001, 11:1–2, 15:13–42). Petitioner asserts that this “does not
`necessarily mean that the iron carbohydrate complex is also substantially
`non-immunogenic in view of the specification, which consistently considers
`separately the immunogenicity of the carbohydrate and the iron complex of
`which it is a part.” Id.
`Patent Owner asserts that a “logical construction of ‘iron carbohydrate
`complex’ requires that the carbohydrate must be substantially non-
`immunogenic in the context of its role as a component in the complex and
`not as an independent carbohydrate,” and “[h]ence, the immunogenicity is
`determined by the complex as a whole.” Prelim. Resp. 20. Patent Owner
`asserts that “[v]iewing the carbohydrate absent the iron . . . would not be
`consistent with the fundamentals of immunology.” Id. at 21. Patent Owner
`further argues that whether a component is “‘non-immunogenic’ can only be
`revealed with a large sample size.” Id. at 23 (emphasis removed).
`We agree with Petitioner that the term “substantially non-
`immunogenic carbohydrate component” only requires an assessment of the
`immunogenicity of the carbohydrate component, and disagree with Patent
`Owner that the claims require an assessment of the immunogenicity of the
`iron carbohydrate complex as a whole. There is nothing in the claim
`language or specification to suggest that “substantially non-immunogenic”
`
`
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`characteristic refers the iron carbohydrate complex as a whole as opposed to
`only the carbohydrate component. To the contrary, the specification teaches
`in the background section that previously available iron dextran products
`suffered from a “high incidence of anaphylactoid reactions . . . believed to
`be caused by the formation of antibodies to the dextran moiety,” while
`“[o]ther parenteral iron products (e.g., iron sucrose and iron gluconate) do
`not contain the dextran moiety, and the incidence of anaphylaxis with these
`products is markedly lower.” Ex. 1001, 1:52–57. It is, therefore, clear that
`the specification’s focus is on obtaining a carbohydrate component that can
`overcome these deficiencies associated with a dextran moiety.
`Thus, based on the present record, we construe “substantially non-
`immunogenic carbohydrate component” as a carbohydrate component
`resulting in a “low risk of anaphylactoid/hypersensitivity reactions.”
`
`2. “single dosage unit”
`Patent Owner argues that the term the term “single dosage unit” in
`claim 1 means an administration of the iron carbohydrate complex that
`delivers the dose of elemental iron in a single administration. Prelim. Resp.
`27. Petitioner has not proposed a construction for this term.
`We agree with Patent Owner’s proposed construction, and find it to be
`consistent with the specification of the ’549 patent. The specification states:
`“The total iron dosage can be delivered as a single unit dosage or a series of
`single unit dosages. An appropriate single unit dosage level will generally
`be at least 0.6 grams of elemental iron . . . .” Ex. 1001, 7:16–26. This is in
`contrast to prior art therapy models wherein “a total dose of 1 g typically
`requires 5 to 10 sessions over an extended period of time.” Id. at 2:14–16.
`
`
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`Thus, based on the present record, we construe “single dosage unit” to
`require a single administration of the requisite amount of elemental iron.
`
`3. Remaining Claim Terms
`We determine that no explicit construction of any other claim term is
`necessary to determine whether to institute a trial in this case. See, e.g.,
`Wellman, Inc. v. Eastman Chem. Co., 642 F.3d 1355, 1361 (Fed. Cir. 2011)
`(“[C]laim terms need only be construed ‘to the extent necessary to resolve
`the controversy.’”) (quoting Vivid Techs., Inc. v. Am. Sci. & Eng’g, Inc.,
`200 F.3d 795, 803 (Fed. Cir. 1999)). At this stage of the proceeding, we
`have not made a final determination as to the construction of any claim term.
`
`B. Anticipation by Vance
`1. Vance (Ex. 1002)
`Vance teaches a method for increasing the hematocrit of a mammal
`undergoing erythropoietin (EPO) treatment, wherein an effective amount of
`iron, in a pharmaceutically acceptable form, is administered in order to
`increase the serum iron content of the mammal. Ex. 1002, Abstract. Vance
`teaches that “[p]arenteral preparations of iron such as solutions of iron
`dextran, iron sorbitex, green ferric ammonium citrate, ferrous gluconate, iron
`adenylate and iron polyisomaltose may also be used.” Id. at 4:35–38.
`Vance further teaches that the administration of iron at a rate of 100–
`1500 mg per day will produce the requisite saturation levels in most normal
`humans, and “[p]referably, the iron should be administered at the rate of
`300–900 mg per day.” Id. at 5:18–21. Vance also teaches that “[a] suitable
`amount of iron sufficient to increase or maintain the serum iron content of
`the patient to an erythropoiesis supportable level is administered to the
`
`
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`patient 14 days prior to EPO therapy at one or more doses per day, for
`example, three times a day.” Id. at 5:31–35.
`
`2. Analysis
`Petitioner asserts that claims 1, 7, 8, 15, 17, and 21 are anticipated by
`Vance. The Petition includes claim charts mapping the teachings of Vance
`to each of these claims. Pet. 29–37.
`We determine that Petitioner has not shown a reasonable likelihood of
`prevailing with respect to this anticipation challenge. In particular,
`Petitioner has not shown how Vance teaches the administration of a “single
`dosage unit of at least about 0.6 grams of elemental iron,” as recited in
`independent claim 1. For this requirement, Petitioner points to the teaching
`in Vance that iron administered at a rate of 100–1500 mg per day, preferably
`at the rate of 300–900 mg per day, will produce the requisite increase in
`saturation levels. Pet. 32 (citing Ex. 1002, 5:18–21). Petitioner further
`relies upon Vance’s teaching that a “suitable amount of iron sufficient to
`increase or maintain the serum iron content” may be administered “at one or
`more doses per day, for example, three times a day.” Id. (citing Ex. 1002,
`5:30–35).
`We do not find that Vance sufficiently teaches the administration of a
`“single dosage unit of at least about 0.6 grams of elemental iron,” as
`required by the claims. As discussed above, “single dosage unit” is properly
`construed to require a single administration of the requisite amount of iron.
`Here, Vance suggests that iron may be administered at rates of 100–1500 mg
`per day, preferably 300–900 mg per day, “at one or more doses per day”
`(emphasis added). This does not necessarily teach, however, that any
`amount of iron within the disclosed range can be administered in a single
`
`
`
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`daily dose. Accordingly, there is no teaching of administering at least 600
`mg (0.6 grams) of iron in a single dosage unit.
`We, therefore, decline to institute inter partes review based on this
`challenge.
`
`C. Anticipation by van Zyl-Smit
`1. van Zyl-Smit (Ex. 1004)
`van Zyl-Smit describes a study in which intravenous iron was given as
`a bolus replacement to hemodialysis patients with anemia. Ex. 1004,
`Abstract. van Zyl-Smit describes the treatment regimen as follows:
`Patients were treated with an iron polymaltose (dextrin)
`preparation (Ferrimed®, Vifor International Inc., Switzerland).
`The dose required was calculated according to body mass and
`haemoglobin concentration using a table supplied by the
`manufacturer and was given as a total dose infusion (TDI). The
`dosage required ranged from 18 to 64 ml (900–3,200 mg of
`iron) and was diluted in 500 ml of normal saline and infused
`over a 4-hour period during a dialysis session.
`
`Id. at 317.5
`In describing any adverse reactions from the treatment, van Zyl-Smit
`teaches:
`
`No anaphylactoid and no delayed reactions such as
`pyrexia, arthralgia, or myalgia were seen. Hypotensive
`episodes were more difficult to assess as these occur frequently
`during the course of normal haemodialysis. At no stage did the
`clinicians responsible for the care of these patients feel that any
`of these episodes were related to the iron infusions, none of the
`infusions had to be stopped and no thrombophlebitis occurred.
`
`
`5 We refer herein to the journal page numbers of the van Zyl-Smit article
`rather than the page numbers added to the Exhibit by Petitioner.
`
`
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`One patient died 19 days after the infusion of complications
`unrelated to the infusion.
`
`Id. at 321.
`
`2. Analysis
`Petitioner asserts that dependent claims 2–5, 9, 16, and 19 are
`anticipated by van Zyl-Smit. Although the Petition does not specifically
`include independent claim 1 as part of this anticipation challenge, we must
`nonetheless consider whether the limitations of the independent claim are
`satisfied before turning to the dependent claims. We, therefore, consider
`claim 1 to be included as part of this challenge. See In re Cuozzo Speed
`Techs., LLC, 793 F.3d at 1275. In this regard, Petitioner has included claim
`charts mapping the teachings of van Zyl-Smit to claim 1 as well as to claims
`2–5, 9, 16, and 19. Pet. 37–46.
`Based on the present record, we determine that Petitioner has shown a
`reasonable likelihood of establishing that claims 1–5, 9, 16, and 19 are
`anticipated by van Zyl-Smit.
`Patent Owner argues that van Zyl-Smit does not teach a “substantially
`non-immunogenic carbohydrate component.” Prelim. Resp. 45–47. We
`disagree. As an initial matter, the iron polyisomaltose (dextrin) disclosed by
`van Zyl-Smit is one of the iron carbohydrate complexes recited in
`independent claim 1. Patent Owner does not explain why the same
`compound that is claimed would not otherwise have the same non-
`immunogenic property. It is well-settled that “[p]roducts of identical
`chemical composition can not have mutually exclusive properties.” In re
`Spada, 911 F.2d 705, 708 (Fed. Cir. 1990); see also In re Papesch, 315 F.2d
`381, 391 (CCPA 1963) (a chemical compound and its properties are
`
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`inseparable). Thus, a disclosure of a specific iron carbohydrate complex is
`likewise a disclosure of its inherent properties, regardless of whether the
`immunogenicity or reactivity of a given complex should be determined on
`the basis of the carbohydrate component individually or the complex as a
`whole.
`Furthermore, in addressing the incidences of “adverse reactions”
`associated with the treatment, van Zyl Smit specifically states that “[n]o
`anaphylactoid and no delayed reactions such as pyrexia, arthralgia, or
`myalgia were seen.” Ex. 1004, 321. We are unpersuaded by Patent Owner’s
`argument that “anaphylactic shock is an extreme reaction, and milder
`immunogenic reactions can occur without triggering anaphylaxis.” Prelim.
`Resp. 45. The ’549 patent itself describes “low risk of
`anaphylactoid/hypersensitivity reactions” among the desirable characteristics
`of iron carbohydrate complexes that are amenable to administration at higher
`doses. Ex. 1001, 10:55–11:2. Indeed, van Zyl-Smit did not observe any
`adverse reactions, anaphylaxis or otherwise, that could be attributable to an
`immunogenic carbohydrate component. We are unpersuaded by Patent
`Owner’s arguments that, in van Zyl-Smit, the administration of iron
`polymaltose resulted in hypotension, which is an adverse reaction described
`in the ’549 patent. Prelim. Resp. 45. Although van Zyl-Smit states that
`hypotensive episodes were more difficult to assess for hemodialysis patients,
`the reference nonetheless states that hypotensive episodes occur frequently
`during the course of haemodialysis, and the clinicians responsible for the
`care of the patients did not feel that any such episodes were related to the
`iron infusions. Ex. 1004, 321. As such, there is an insufficient basis on this
`record to conclude that any hypotensive episodes were attributable to the
`
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`administration of iron polymaltose described in van Zyl-Smit. We also have
`considered, but are not persuaded by, Patent Owner’s reliance the Ferrosig
`data sheet from 2003, which indicates that “[p]arenterally administered iron
`preparations can cause allergic or anaphylactoid reactions” and lists
`hypotension as an adverse effect. Prelim. Resp. 46 (citing Ex. 2003, 4–5).
`The fact that the data sheet for a different formulation of iron polymaltose,
`used for intramuscular injection, indicated potential adverse reactions is
`insufficient evidence that the iron polymaltose preparation (Ferrimed)
`administered using the treatment regimen described by van Zyl-Smit caused
`adverse immune reactions.
`Finally, we are unpersuaded by Patent Owner’s argument that, due to
`its 62-patient sample size, “van Zyl-Smit lacks a sufficiently large sample
`size to identify a dangerous adverse event occurring in less than 1% of the
`population.” Id. The claim only requires a “substantially non-immunogenic
`carbohydrate component,” and there is no indication in the ’549 patent that
`this must prevent adverse reactions in all patients under all conditions.
`Contrary to Patent Owner’s argument, there is nothing in the ’549 patent to
`suggest that a minimum patient sample size must be evaluated in order to
`determine whether the iron carbohydrate complex has a substantially non-
`immunogenic carbohydrate component. On this record, we find that the
`results presented in van Zyl-Smit are sufficient to demonstrate that the iron
`polymaltose that was administered has a substantially non-immunogenic
`dextrin component.
`With respect to dependent claim 2, Patent Owner argues that “van
`Zyl-Smit does not teach an iron carbohydrate complex having substantially
`no cross-reactivity with anti-dextran antibodies.” Prelim. Resp. 47. Patent
`
`
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`Owner further argues that Petitioner and its witness do not provide any basis
`or support for the conclusion that “the dextrin in van Zyl-Smit would not
`induce any cross-reactivity with anti-dextran antibodies and would also be a
`‘substantially non-immunogenic carbohydrate component.’” Id. However,
`Petitioner’s expert, Dr. Linhardt, has offered testimony, which is unrebutted
`at this stage, attesting that he would not expect an anti-dextran antibody to
`cross-react with iron polymaltose (dextrin), in which the carbohydrate is a
`primarily α-1-4 linked oligomer or polymer of glucose. Ex. 1014 ¶ 25. We
`find this to be sufficient for institution.
`We, therefore, institute inter partes review as to claims 1–5, 9, 16, and
`19 based on this challenge.
`
`D. Anticipation by Groman
`1. Groman (Ex. 1003)
`Groman relates generally to the use of polyol and polyether iron oxide
`complexes as pharmacological and/or MRI contrast agents. Ex. 1003, Title.
`Groman teaches that “compositions of the invention can serve as an iron
`supplement for patients suffering from anemia . . . .” Id. ¶ 82. Groman
`teaches that the iron oxide complex can be parenterally administered at a
`rate “for a total single dose from about 50 mg to about 600 mg.” Id. ¶ 16.
`Additionally, Groman teaches that “[t]he formulations of the present
`invention are prepared such that upon administration to a patient the iron
`oxide complex presents as an immunosilent agent to the patient, as indicated
`by the patient’s physical response and confirmed by ELISA assay.” Id. ¶
`174. The iron oxide complex used by Groman can be coated with a reduced
`dextran, for example, a reduced carboxymethyl dextran. Id. ¶ 31.
`
`
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`Furthermore, Groman teaches that “[c]hanging the Fe(III)/Fe(II) ratios
`changes the particle size and alters the magnetic susceptibility.” Id. ¶ 100.
`In “Example 28,” Groman teaches that the reduced dextran T1-coated
`ultrasmall superparamagnetic iron oxide (USPIO) particles had a mean
`volume diameter of 18 nm. Id. ¶ 231.
`With respect to the rate of administration, Groman teaches that the
`polyol or polyether iron oxide complex composition [can be]
`prepared at concentrations of between about 1 mg/kg of body
`weight to about 4 mg/kg of body weight in a total volume of
`biocompatible liquid from about 1 mL to about 15 mL and for a
`total single dose from about 50 mg to about 600 mg, wherein
`the pharmacological composition is capable of being
`parenterally administered to a subject at a rate substantially
`greater than 1 mL/min, or alternatively at a rate of about 1
`mL/sec, and wherein the iron oxide complex provides upon
`administration minimal detectable free iron in the subject and
`minimal incidence of anaphylaxis.
`
`Id. ¶ 16.
`
`2. Analysis
`Petitioner asserts that claims 10 and 12–14 are anticipated by Groman.
`Pet. 46–56.6 As with the challenge based on van Zyl-Smit, we must
`necessarily consider whether the limitations of the independent claim are
`satisfied before turning to the dependent claims, and therefore, consider
`claim 1 to be included as part of this challenge. In this regard, Petitioner has
`included claim charts mapping the teachings of Groman to claim 1, as well
`as to claims 10, 12, 13, and 14. Id. at 48–51, 53–54, 56.
`a. Claim 1
`
`6 Although Petitioner presents its anticipation challenges based on Groman
`as two separate “grounds,” we treat them together for purposes of our
`analysis.
`
`
`
`15
`
`PGR2020-00009
`Pharmacosmos A/S v. American Regent, Inc.
`Petitioner Ex. 1096 - Page 15
`
`
`
`IPR2015-01493
`Patent 8,431,549 B2
`
`
`Based on the evidence of record, we determine that Petitioner has
`shown a reasonable likelihood of establishing that claim 1 is anticipated by
`Groman. With respect to the independent claim, Patent Owner’s only
`argument is that Groman does not specifically teach a “single dosage unit of
`at least about 0.6 grams of elemental iron.” Prelim. Resp. 48–50. In
`particular, Patent Owner argues that “the Groman reference appears to
`instruct a [person of ordinary skill in the art] to stop administration around
`600 mg – the upper endpoint of the disclosed range – whereas this is exactly
`the lower endpoint at which the present claims instruct to start
`administration.” Id. at 49.
`We disagree. Groman specifically teaches the administration of a
`total single dose of iron from about 50 mg to about 600 mg, and more
`preferably a total dose of about 500 mg to about 600 mg. Ex. 1003 ¶¶ 15–
`16. Thus, the upper end of the range disclosed by Groman (“about 600 mg”)
`satisfies the requirement of “at least about 0.6 grams of elemental iron.”
`We find Atofina v. Great Lakes Chemical Corp., 441 F.3d 991 (Fed.
`Cir. 2006) relied upon by Patent Owner, to be distinguishable. Prelim. Resp.
`49–50. In Atofina, the Court of Appeals for the Federal Circuit reversed the
`district court’s finding of anticipation where the claims recited temperature
`between 330–450 degrees Celsius and the prior art disclosed a “broad[]
`temperature range” of 100–500 degrees Celsius. Atofina, 441 F.3d at 998–
`99. The key to the court’s conclusion in Atofina “was the fact that the
`evidence showed that a person of ordinary skill in the art would have
`expected the [method] to operate differently, or not all, outside of the
`temperature range claimed in the patent-in-suit.” Ineos USA LLC v. Berry
`Plastics Corp., 783 F.3d 865, 869 (Fed. Cir. 2015) (citing Atofina, 441 F.3d
`
`
`
`16
`
`PGR2020-00009
`Pharmacosmos A/S v. American Regent, Inc.
`Petitioner Ex. 1096 - Page 16
`
`
`
`IPR2015-01493
`Patent 8,431,549 B2
`
`at 999; ClearValue, Inc. v. Pearl River Polymers, Inc., 668 F.3d 1340, 1345
`(Fed. Cir. 2012)). Here, even assuming that Groman’s disclosed range does
`not constitute a specific disclosure of the end point of 600 mg, there is
`insufficient evidence of record demonstrating the criticality of the claimed
`amount of “at least about 0.6 grams,” or otherwise any difference from the
`overlapping range disclosed in the prior art. See ClearValue, 668 F.3d at
`1345 (explaining the importance of establishing the criticality of a claimed
`range to the claimed invention in order to avoid anticipation by a prior art
`reference disclosing a broader range); see also Ineos, 783 F.3d at 870
`(finding that patentee failed to establish that certain properties would differ
`if range from prior art patent was substituted for range of limitation);
`OSRAM Sylvania, Inc. v. Am. Induction Techs., Inc., 701 F.3d 698, 705−06
`(Fed. Cir. 2012) (emphasizing that “how one of ordinary skill in the art
`would understand the relative size of a genus or species in a particular
`technology is of critical importance”).
`b. Claim 10
`Dependent claim 10 requires that “the single dosage unit of elemental
`iron is administered in about 15 minutes or less.” To satisfy this limitation,
`Petitioner points to Groman’s disclosure that the pharmacological
`composition containing a total single dose from about 50 mg to about 600
`mg “is capable of being parenterally administered to a subject at a rate
`substantially greater than 1 mL/min, or alternatively at a rate of about 1
`mL/sec. . . [.]” Pet. 54 (citing Ex. 1003 ¶ 16). Petitioner further relies upon
`the testimony of its declarant, Dr. Robert J. Linhardt, to support its position
`that this disclosure in Groman satisfies the rate of administration required by
`
`
`
`17
`
`PGR2020-00009
`Pharmacosmos A/S v. American Regent, Inc.
`Petitioner Ex. 1096 - Page 17
`
`
`
`IPR2015-01493
`Patent 8,431,549 B2
`
`claim 10. Pet. 53 (citing Ex. 1014 ¶¶ 18, 22). In particular, Dr. Linhardt
`states:
`As regards rate of administration, Groman discloses iron oxide
`polyol at iron concentrations of about 1-4 mg/kg of body
`weight in a total volume of about 1-15 ml (Ex. 1003 at
`paragraph [0016] on pages 16-17). For a human weighing 80
`kg (approximately 176 pounds), this would correspond to
`dilution of 80-320 mg in 1-15 ml. If the greatest amount were
`incorporated in the largest volume, 320 mg would be contained
`in 15 ml. Groman further discloses a total single dose of
`elemental iron from about 50 mg to 600 mg, and a parenteral
`rate of administration “substantially greater than 1 mL/min,” or
`a rate of 1 ml/second (Ex. 1003 at paragraph [0016] on pages
`16-1 7). A dose of 600 mg, at a dilution of 320 mg per 15 ml,
`would be contained in 28.2 ml. Administration of the 600 mg
`dose at a rate of 1 ml/sec would occur over 28.2 seconds, and at
`a rate of “substantially greater than 1 mL/min” would occur in
`(substantially) less than 28 minutes. If a more concentrated
`solution (as contemplated in the disclosed ranges) were
`administered, the infusion time would be shorter, and with a
`more dilute solution, the infusion time would be longer. Thus,
`Groman teaches administration of a single dose of iron
`carbohydrate complex (iron carboxymethyl reduced dextran
`(iron polyglucose sorbitol carboxymethyl ether complex) or of
`hydrogenated (reduced) dextran having, for example, having a
`molecular weight of about 1000 Da) - of up to 0.6 grams, in less
`than 28 minutes, in less than fifteen minutes, in less than five
`minutes, in less than two minutes, and even in less than one
`minute.
`
`Ex. 1014 ¶ 22. Dr. Linhardt’s analysis requires several assumptions upon
`assumptions to be made in order to arrive at the claimed administration rate
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