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` Paper 11
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` Entered: January 8, 2016
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`Trials@uspto.gov
`571-272-7822
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`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`PHARMACOSMOS A/S,
`Petitioner,
`
`v.
`
`LUITPOLD PHARMACEUTICALS, INC.,
`Patent Owner.
`
`
`Case IPR2015-01495
`Patent 8,895,612 B2
`
`
`
`Before TONI R. SCHEINER, LORA M. GREEN, and
`CHRISTOPHER G. PAULRAJ, Administrative Patent Judges.
`
`SCHEINER, Administrative Patent Judge.
`
`
`DECISION
`Denying Institution of Inter Partes Review
`37 C.F.R. § 42.108
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`IPR2015-01495
`Patent 8,895,612 B2
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`I. INTRODUCTION
`Pharmacosmos A/S (“Petitioner”) filed a Petition (Paper 1, “Pet.”) on
`June 24, 2015, requesting an inter partes review of claims 1–5, 7, 8, 11, 12,
`15–17, and 20 of U.S. Patent No. 8,895,612 B2 (Ex. 1001, “the ’612
`patent”). Luitpold Pharmaceuticals, Inc. (“Patent Owner”) filed a
`Preliminary Response (Paper 7, “Prelim. Resp.”) on October 12, 2015. 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 information presented in the Petition and
`the Preliminary Response, we conclude that Petitioner has not established a
`reasonable likelihood that it would prevail in its challenges to at least one of
`the claims of the ’612 patent. Accordingly, we decline to institute an inter
`partes review of the challenged claims.
`
`A. Related Proceedings
`Concurrently with the Petition under consideration here, Petitioner
`
`also filed Petitions for inter partes review challenging the claims of related
`U.S. Patent Nos. 7,754,702 B2 and 8,431,549 B2. IPR2015-01490,
`IPR2015-01493, respectively. Paper 6. Neither party identifies any other
`judicial or administrative matter that would affect, or be affected by, a
`decision in this proceeding.
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`B. The Asserted Grounds of Unpatentability
`Petitioner asserts the challenged claims are unpatentable on the
`
`following grounds. Pet. 28–59.
`
`References
`
`Groman1
`
`Marchasin3
`Geisser5 and Groman
`Groman and van Zyl-Smit6
`
`Basis
`
`Claims Challenged
`
`§ 102(b)
`§ 102(b)
`§ 103(a)
`§ 103(a)
`
`
`1–5, 15, 16, and 202
`204
`7, 11, and 12
`8 and 17
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`
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`1 US 2003/0232084 A1, published December 18, 2003 by Groman et al.
`(“Groman”) (Ex. 1002).
`2 Petitioner presents its anticipation challenges based on Groman as two
`separate grounds (Pet. 28–39, 42–46), but we discuss the challenges together
`for purposes of this analysis.
`3 Sidney Marchasin & Ralph O. Wallerstein, The Treatment of Iron-
`Deficiency Anemia with Intravenous Iron Dextran, 23 BLOOD 354–358
`(1964) (“Marchasin”) (Ex. 1005).
`4 For reasons discussed below, we treat this challenge as including claim 1,
`from which claim 20 depends.
`5 Certified English translation of WO 2004/037865 A1, published May 6,
`2004 by Geisser et al. (“Geisser”) (Ex. 1004).
`6 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 316–323 (2002) (“van
`Zyl-Smit”) (Ex. 1006).
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`C. The ’612 Patent (Ex. 1001)
`The ’612 patent, titled “Methods and Compositions for
`Administration of Iron,” discloses parenteral administration of iron
`carbohydrate complexes “at relatively high single unit dosages for the
`therapeutic treatment of a variety of iron-associated diseases, disorders, or
`conditions” (Ex. 1001, 5:28–30), e.g., iron deficiency anemia, anemia of
`chronic disease, and dysfunctional iron metabolism (id. at 5:33–35).
`The ’612 patent teaches that various prior art parenteral iron
`formulations, e.g., iron dextran, sodium ferric gluconate complex in sucrose,
`and iron sucrose, “while purportedly effective at repleting iron stores, have
`health risks and dosage limitations associated with their use.” Id. at 1:37–
`43. “[S]erious and life-threatening reactions occur most frequently with iron
`dextran” (id. at 1:43–44), and the “high incidence of anaphylactoid reactions
`is believed to be caused by the formation of antibodies to the dextran
`moiety” (id. at 1:57–58). Iron sucrose and iron gluconate “do not contain
`the dextran moiety, and the incidence of anaphylaxis with these products is
`markedly lower” (id. at 1:59–61), but certain of their physical characteristics
`“lead to dosage and administration rate limitations” (id. at 1:64–66). For
`example, “[v]arious pharmacokinetic studies suggest that doses of iron
`complexes higher than 200 mg of iron are generally unsuitable and . . . the
`conventional therapy model prescribes repeated applications of lower doses
`over several days.” Id. at 2: 13–16.
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`According to the ’612 patent, however, certain iron carbohydrate
`complexes can be administered at doses of “at least 0.6 grams [600
`micrograms (mg)] of elemental iron via a single unit dosage” (id. at 2:40–
`42), “in 15 minutes or less” (id. at 7:45–46), without significant adverse
`reactions (id. at 15:20–46), “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 2:33–36). The ’612 patent further explains:
`Preferably, iron carbohydrate complexes for use in the methods
`disclosed herein are those which have one or more of the
`following characteristics: 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 10:64–11:8.
`
`The ’612 patent teaches that suitable iron carbohydrate complexes
`include iron carboxymaltose complex, iron mannitol complex, iron
`polyisomaltose complex, iron polymaltose complex, iron sorbitol complex,
`iron polyglucose sorbitol carboxymethyl ether complex. Id. at 3:40–43.
`
`D. Illustrative Claim
`Petitioner challenges claims 1–5, 7, 8, 11, 12, 15–17, and 20 of the
`’612 patent. Claims 1 and 20, reproduced below, are illustrative.
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`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 carboxymaltose complex, an iron mannitol
`complex, an iron polyisomaltose complex, an iron polymaltose
`complex, an iron sorbitol complex, and an iron polyglucose
`sorbitol carboxymethyl ether complex;
`the single dosage unit of elemental iron is administered in
`about 15 minutes or less; and
`the iron carbohydrate complex has a substantially non-
`immunogenic carbohydrate component.
`20. The method of claim 1, wherein the iron carbohydrate
`complex is an iron polyisomaltose complex.
`Ex. 1001, 26:29–46, 28:36–37.
`
`II. ANALYSIS
`A. Claim Construction
`In an inter partes review, claim terms in an unexpired patent are
`interpreted according to their broadest reasonable construction in light of the
`specification of the patent in which they appear. 37 C.F.R. § 42.100(b);
`Office Patent Trial Practice Guide, 77 Fed. Reg. 48,756, 48,766 (Aug. 14,
`2012); In re Cuozzo Speed Techs., LLC, 793 F.3d 1268, 1275–79 (Fed. Cir.
`2015). Under that standard, claim terms are given their ordinary and
`customary meaning, as would be understood by one of ordinary skill in the
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`art in the context of the entire disclosure. In re Translogic Tech., Inc., 504
`F.3d 1249, 1257 (Fed. Cir. 2007). “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).
`We determine that no claim term requires express construction for
`purposes of this Decision, except to the extent the term “iron polyisomaltose
`complex” is discussed below in the context of the challenge to claim 20
`based on Marchasin. 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)).
`
`B. Claims 1–5, 15, 16, and 20—Asserted
`Anticipation by Groman
`1. Groman (Ex. 1002)
`Groman teaches that “prior art complexes of dextran and iron oxide
`can be made that have minimal detectable free iron, and other complexes of
`iron oxide may have minimal incidence of anaphylaxis, [but] no prior art
`complexes of iron oxide have both properties.” Ex. 1002 ¶ 5. According to
`Groman, however, a “polysaccharide such as dextran, when reduced and
`carboxyalkylated [e.g., carboxymethyl reduced dextran ] can be complexed
`with iron oxide to produce a composition that continues (like dextran iron
`oxide) to have minimal detectable free iron in a subject, while (unlike
`dextran iron oxide) also having minimal incidence of anaphylaxis.” Id. ¶¶ 5,
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`31. That is, Groman’s formulations “present[] as an immunosilent agent to
`the patient, as indicated by the patient’s physical response and confirmed by
`ELISA assay.” Id. ¶ 174.
`With respect to the rate of administration, Groman teaches that the
`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
`
`Claim 1
`Claim 1 is directed to a method of treating a disease, disorder, or
`condition characterized by iron deficiency or dysfunctional iron metabolism
`comprising administering an iron carbohydrate complex in a single dosage
`unit of at least about 0.6 grams of elemental iron in fifteen minutes or less,
`where the iron carbohydrate complex can be an iron polyglucose sorbitol
`carboxymethyl ether complex, and the carbohydrate component of the
`complex is substantially non-immunogenic.
`Petitioner asserts that claim 1 is anticipated by Groman (Pet. 28–32),
`and provides a claim chart mapping portions of Groman’s disclosure to the
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`limitations of claim 1 (id. at 31–32). Petitioner contends that Groman
`discloses treatment of anemia by administering an iron carboxymethyl
`reduced dextran (CMRD) complex (id. at 29 (citing Ex. 1002 ¶¶ 8, 31, 38,
`44, 45, 47–52, 82, 272–294, 333–353)), which Petitioner asserts “is an
`example of a polyglucose sorbitol carboxymethyl ether” complex (id. (citing
`Ex. 10137 ¶¶ 20–21)). Petitioner further contends that “Groman discloses
`administering the iron-polyglucose sorbitol carboxymethyl ether complexes
`in a single dose of up to about 0.6 g iron” (id. at 29 (citing 1002 ¶¶ 15–16)),
`“in a time interval that includes about 15 minutes or less” (id. at 31 (citing
`Ex. 1002, ¶ 16; Ex. 1013 ¶ 22)). Finally, Petitioner contends that Groman’s
`iron-polyglucose sorbitol carboxymethyl ether complex is “substantially
`non-immunogenic” (id. at 30 (citing Ex. 1002 ¶ 336, Table 18)), noting that
`Groman teaches that the complexes “are ‘immunosilent’ and have ‘minimal
`incidence of anaphylaxis’” (id. (citing Ex. 1002 ¶¶ 4–7, 9–12, 15, 16, 66, 89,
`104)).
`Patent Owner argues that Groman does not specifically disclose that
`“the single dosage unit of elemental iron is administered in about 15 minutes
`or less,” as required by claim 1. To satisfy this limitation, Petitioner relies
`on Groman’s disclosure that a single dose containing from about 50 mg to
`about 600 mg of elemental iron “is capable of being parenterally
`administered to a subject at a rate substantially greater than 1 mL/min, or
`
`
`7 Declaration of Robert Linhardt, Ph.D., executed June 22, 2015 (“Linhardt
`Declaration”) (Ex. 1013).
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`alternatively at a rate of about 1 mL/sec.” Pet. 32 (citing Ex. 1002 ¶ 16).
`Petitioner further relies upon the testimony of its witness, Dr. Robert
`Linhardt, to support its position that this disclosure in Groman satisfies the
`rate of administration required by claim 1. Pet. 30 (citing Ex. 1013, ¶ 22).
`In particular, Dr. Linhardt states that:
`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 16–17). 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. 1013 ¶ 22.
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`Dr. Linhardt’s analysis, however, rests on a series of assumptions in
`order to arrive at the claimed administration rate of fifteen minutes or less.
`For example, one must first assume a subject weighing eighty kilograms,
`then choose to incorporate the greatest possible amount of the iron oxide
`polyol (320 mg) in the largest volume (15 ml), then further increase the total
`single dose to 600 mg (0.6 grams) using the same dilution, and then choose a
`shorter administration time from the broader calculated range of less than 28
`minutes. At best, Dr. Linhardt’s testimony establishes that it is possible to
`arrive at the requisite amount and rate by selecting a particular combination
`of variables disclosed by Groman. Such picking and choosing, however, is
`improper in the context of an anticipation challenge. See In re Arkley, 455
`F.2d 586, 587 (CCPA 1972).
`
`We determine that Petitioner has not established that Groman
`discloses administering a single dosage unit of at least about 0.6 grams of
`elemental iron in about 15 minutes or less, as required by claim 1, and
`therefore, has not demonstrated a reasonable likelihood of establishing that
`Groman anticipates claim 1.
`Claims 2–5, 15, 16, and 20
`
`
`Each of these claims depends directly or indirectly from claim 1, and,
`therefore, incorporates the requirement that the iron carbohydrate complex is
`administered in fifteen minutes or less. Accordingly, the challenge to these
`claims suffers from the same deficiency as the challenge to claim 1.
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`For the foregoing reasons, we conclude that Petitioner has not
`demonstrated a reasonable likelihood of showing that claims 1–5, 15, 16,
`and 20 are anticipated by Groman.
`
`C. Claim 20—Asserted Anticipation by Marchasin
`1. Marchasin (1005)
`Marchasin discloses intravenous administration of iron-dextran to 37
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`patients with iron deficiency and to 8 patients with acute gastrointestinal
`bleeding. Ex. 1005, 357.
`iron-dextran
`All patients were given undiluted
`intravenously. The compound was administered in a single
`dose of 2000–3000 mg. (6 patients), 1000 mg. (18 patients),
`100–500 mg. (7 patients), and in repeated doses of 250–500
`mg., 2–4 times in 2 weeks (6 patients). Iron was given by slow
`intravenous drip infusion to the first few patients, the remainder
`received the preparation by injection over a 4–10 minute period.
`Id. at 355. “No serious untoward effects were observed.” Id. at 357.
`According to Marchasin, the iron-dextran used was “a combination of
`colloidal ferric hydroxide with dextran of a molecular weight of
`approximately 2000 to 8000.” Id. at 355–56.
`2. Analysis
`Petitioner asserts that claim 20, which specifies that the iron
`carbohydrate complex is an iron polyisomaltose complex, is anticipated by
`Marchasin. Pet. 39–42.
`Claim 20 depends from claim 1. A disclosure that anticipates a
`properly dependent claim necessarily anticipates the claim from which it
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`depends. Moreover, Petitioner provides a claim chart for this challenge
`mapping portions of Marchasin’s disclosure to the limitations of claims 1
`and 20. Pet. 41–42. Consequently, we consider claim 1 as part of this
`challenge.
`Petitioner’s challenge, as applied to both claims 1 and 20, is based on
`the assertion that “iron polyisomaltose and iron dextran should be regarded
`as synonyms for the purpose of claim construction” (Pet. 13), “[b]ecause the
`specification states that ‘[e]xamples of iron carbohydrate complexes include
`. . . iron polyisomaltose (iron dextran),’ and because the specification
`provides no basis for differentiating between them” (id. (citing 1001,
`10:54)). Petitioner acknowledges that “there are instances[ ] where
`‘polyisomaltose’ is used to refer to dextran that has been processed to
`remove most or all of its branches” (id. at 14), but contends “[r]egardless of
`the meaning of this term to those of ordinary skill in the art, the patentee
`here explicitly defined polyisomaltose in the specification to be
`interchangeable with dextran, and that definition should control” (id. at 13
`n.6).
`
`Patent Owner contends that “the parenthetical ‘dextran’ should not be
`considered to indicate equivalence” (Prelim. Resp. 30), and that Petitioner’s
`construction is inconsistent with the understanding in the art of the term
`polyisomaltose, and with the specification of the ’612 patent (id. at 29).
`Patent Owner contends that there is ample evidence of record that the two
`terms are not freely interchangeable (id.), and that “Petitioner’s construction
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`also ignores the disparaging remarks about dextran in the specification”
`(id.at 30). For example, Patent Owner points to the statement in U.S. Patent
`No. 3,100,202 to Müller, issued August 6, 1963, and cited by the Examiner
`during prosecution: “While ‘polyisomaltose’ is a term used loosely for
`‘dextran’ . . . the latter is a compound of very high molecular weight,
`whereas polyisomaltose is a degradation product of dextran consisting of
`polymerized glucose residues joined predominantly by 1,6 linkages.”
`Prelim. Resp. 28 (citing Ex. 1010, 2:48–53). We further note statements in
`the ’612 patent to the effect that “serious and life-threatening reactions occur
`most frequently with iron dextran” (Ex. 1001, 1:43–44); “[i]ron dextran . . .
`has been associated with an incidence of anaphylactoid-type reactions” (id.
`at 1: 51–53); and “[t]his high incidence of anaphylactoid reactions is
`believed to be caused by the formation of antibodies to the dextran moiety”
`(id. at 1:56–58). Finally, we note that the’612 patent emphasizes that the
`iron carbohydrate complexes of the invention preferably have various
`characteristics—including a “non-immunogenic carbohydrate component”
`and “substantially no cross-reactivity with anti-dextran antibodies” (id. at
`3:28–31).
`Having considered the evidence of record, we agree with Patent
`Owner that Petitioner has not established adequately that the claim term
`“iron polyisomaltose” would be understood by one of ordinary skill in the
`art in the context of the entire disclosure of the ’612 patent to encompass
`Marchasin’s “iron-dextran.” Therefore, we are not persuaded that Petitioner
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`has established that Marchasin discloses administering an iron
`polyisomaltose complex.
`Accordingly, we conclude that Petitioner has not demonstrated a
`reasonable likelihood of showing that claims 1 and 20 are anticipated by
`Marchasin.
`
`D. Claims 7, 11, and 12—Asserted Obviousness
`over Geisser and Groman
`1. Geisser (Ex. 1004)
`Geisser discloses “a water-soluble iron-carbohydrate complex
`obtained from an aqueous iron(III)-salt solution and an aqueous solution of
`the product obtained by oxidizing one or several maltodextrins with an
`aqueous hypochlorite solution at an alkaline pH value” and “a method for
`the production of said complex and medicaments for the treatment and
`prophylaxis of iron deficiencies.” Ex. 1004, 2:3–6, 10–12.8
`Geisser teaches that the complexes are “particularly suitable for
`parenteral use” (id. at 3:7–8), and have the advantage of “low toxicity and a
`reduced risk of anaphylactic shock” (id. at 10:9). Geisser also teaches that it
`is possible to administer medications containing the complexes as a single
`dose of 500 mg to 1000 mg over the course of an hour. Id. at 10:16–17.
`
`
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`8 Ex. 1004 is a certified English translation of the original German language
`document, WO 2004/037865 A1, and includes the Translator Certification as
`the first page of the Exhibit. Petitioner cites to the page numbers shown in
`the lower right-hand portion of the Exhibit, rather than the page numbers of
`the translation, and we do the same for Exhibit 1004 only.
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`1. Analysis
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`
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`Claims 7, 11, and 12
`Claim 7 depends from claim 1 and requires that the single dosage unit
`of elemental iron is at least about 1.0 grams. Claim 11 also depends from
`claim 1 and requires that the iron carbohydrate complex is an iron
`carboxymaltose complex. Claim 12 depends from claim 11, and requires an
`iron carboxymaltose complex with a particular formula.
`Petitioner contends that Geisser’s complexes, obtained by oxidizing
`maltodextrin(s), are iron carboxymaltose complexes, although Geisser does
`not use that exact term. Pet. 25–26 (citing Ex. 1013 ¶¶ 24–26). Petitioner
`notes that Geisser discloses that the iron carboxymaltose complexes “have
`high stability and low toxicity (so that they can be used at higher doses [of
`500–1000 mg iron]) and [have] reduced danger of anaphylactic shock which
`can be induced by dextran.” Pet. 48 (citing Ex. 1004, 3:26–28, 10:7–10).
`According to Petitioner’s witness, Dr. Linhardt, Geisser’s
`carboxymaltose and Groman’s carboxymethylated reduced dextran (CMRD)
`are “structurally analogous” (Ex. 1013 ¶ 30). Dr. Linhardt points to Figures
`E and I of his Declaration9 in support of this assertion, but offers little or no
`explanation, except to state that both complexes would be expected to form
`tight, stable complexes with iron, and “consequently, . . . would be expected
`
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`9 According to Dr. Linhardt, Figure E of the Declaration depicts the
`structure and molecular formula of carboxymethylated reduced dextran
`(CMRD), and Figure I depicts the structure and molecular formula of
`Geisser’s carboxymaltose. Ex. 1013 ¶¶ 30, 31.
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`[to] yield low levels of free iron and therefore would be unlikely to produce
`undesirable toxic effects” (id. ¶¶ 30–32).
`Relying on Dr. Linhardt’s testimony, Petitioner contends that “[i]t
`would have been obvious for one of ordinary skill in the art to substitute iron
`carboxymaltose at a dose of 1.0 g iron of Geisser into the method of
`Groman” (Pet. 48 (citing Ex. 1013 ¶ 32)), and “to administer the larger doses
`disclosed by Geisser, for example a dose providing 1 g of elemental iron,
`within about 15 minutes or less, based on Groman” (id.), because “[t]he
`carboxymethylated dextran disclosed in Groman is structurally analogous to
`the carboxymaltose disclosed in Geisser, and used for essentially the same
`purpose” (id. (citing Ex. 1013 ¶¶ 30–32)).
`
`Patent Owner contends that “Geisser does not disclose that the iron
`carbohydrate complex can be administered at a rate of ‘about 15 minutes or
`less’ as required by independent claim 1” (Prelim. Resp. 52), “[r]ather,
`Geisser discloses that the ‘single dose . . . can be applied over the course of 1
`hour’” (id.). Moreover, Patent Owner contends that “Groman and Geisser
`relate to different iron carbohydrate complexes” (id. at 54), and “Petitioner’s
`‘structurally analogous’ arguments . . . are not based on any evidence or
`scientific basis” (id. at 55). According to Patent Owner,
`The carbohydrate component of Groman is different from
`the carbohydrate component of Geisser. As noted by the
`Petitioner, Geisser’s
`carbohydrates
`are derived
`from
`maltodextrin. Petition, p. 13, which has α-1-4 linkages between
`glucose monomers. Ex. 1013, p. 18. In contrast, the
`
`17
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`IPR2015-01495
`Patent 8,895,612 B2
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`carbohydrates in Groman are derived from dextran, which has
`α-1-6 linkages between glucose monomers.
`Id. at 54. Patent Owner contends that “the carbohydrates of Groman and
`Geisser . . . would be expected to bind to the iron core differently, i.e., with
`different strengths and presenting different antigenic moieties” (id. at 55),
`and “[u]nderstanding these differences, a [person of ordinary skill in the art]
`would not have any motivation to combine Geisser and Groman” (id.).
`We agree with Patent Owner that Petitioner has not established that
`one of ordinary skill in the art would have had a reason to combine the
`teachings of Geisser and Groman in the manner required by the challenged
`claims. As discussed above in connection with the anticipation challenge of
`claim 1 based on Groman, Petitioner has not established that Groman
`discloses administering a single dosage unit of at least about 0.6 grams of
`elemental iron in about 15 minutes or less, as required by claim 1. Nor has
`Petitioner explained why it would have been obvious for one of ordinary
`skill in the art to choose, from all the variables disclosed in Groman, those
`parameters that would result in administering at least about 0.6 grams of
`elemental iron in less than fifteen minutes, much less an even larger dose of
`at least about 1.0 gram.
`Having considered the information presented in the Petition, and
`Patent Owner’s Preliminary Response, we are not persuaded that Petitioner
`has demonstrated a reasonable likelihood that it would prevail in showing
`that challenged claims 7, 11, and 12 are unpatentable over Geisser and
`Groman.
`
`18
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`E. Claims 8 and 17—Asserted Obviousness over
`Groman and van Zyl-Smit
`1. van Zyl-Smit (Ex. 1006)
`Van Zyl-Smit describes a study in which intravenous iron was given
`
`as a bolus replacement to anemic hemodialysis patients. Ex. 1006, 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 500ml of normal saline and infused
`over a 4-hour period during a dialysis session.
`Id. at 317.
`
`According to van Zyl-Smit, “[t]he iron polymaltose (dextrin)
`preparation (Ferrimed) used in [the] study releases iron more slowly [than
`compounds such as iron sucrose and iron gluconate] and allows the use of
`[total dose infusion]” with “minimal free iron related side effects with high
`doses used with [total dose infusion].” Id. at 322.
`2. Analysis
`
`Claims 8 and 17
`Claim 8 depends from claim 1 and requires that the single dosage unit
`of elemental iron is at least about 1.5 grams. Claim 17 depends from claim
`16 (which depends from claim 1) and requires that the iron carbohydrate
`complex is administered within certain concentration ranges.
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`Petitioner contends van Zyl-Smit and Groman “both relate to iron
`carbohydrate complexes with minimal free iron that can be administered at
`high doses for treatment of iron deficiency, [thus] a [person of ordinary skill
`in the art] would have been motivated to combine their teachings.” Pet. 57
`(citing Ex. 1013 ¶ 34). Specifically, Petitioner contends it would have been
`obvious for one of ordinary skill in the art “to administer a single unit
`dosage of at least about 1.5 g iron (within the 900-3200 mg range taught by
`van Zyl-Smit) in the form of iron polymaltose complex in about 15 minutes
`or less with a reasonable expectation of success (low free iron and low
`toxicity).” Id.
`Patent Owner contends that van Zyl-Smit “teaches the slow infusion
`(over four hours) of an iron polymaltose preparation.” Prelim. Resp. 56.
`Patent Owner contends, “to make up for the slow administration speed of
`van Zyl-Smit, Petitioner relies on Groman . . . for teaching speed of
`administration . . . at a rate of ‘substantially greater than 1 mL/min, or
`alternatively, a rate of about 1 mL/sec’” (id. at 58), but Groman “does not
`teach the administration of high doses of iron carbohydrate complex over a
`period of 15 minutes or less” (id. at 60).
`In addition, Patent Owner contends that “the carbohydrate in
`Groman’s complex is derived from dextran, while the carbohydrate in van
`Zyl-Smit’s complex is derived from a dextrin.” Id. at 58. Patent Owner
`contends that “[a] polymaltose is a polymer in which the glucose units are
`linked primarily through α-1-4 linkages” (id. at 59 (citing Ex. 1002 ¶ 5)),
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`20
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`IPR2015-01495
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`while “the carbohydrates in Groman are derived from dextran, which has α-
`1-6 linkages between glucose monomers” (id.). Patent Owner contends that
`one of ordinary skill in the art “would not have been motivated to combine
`the teachings of van Zyl-Smit with Groman because they are directed to two
`different complexes that would, thus, be expected to have different
`properties.” Id. at 59.
`Again, we agree with Patent Owner that Petitioner has not established
`that one of ordinary skill in the art would have had a reason to combine the
`teachings of Groman and van Zyl-Smit in the manner required by the
`challenged claims. As discussed above in connection with the challenge of
`claim 1 as anticipated by Groman, Petitioner has not established that
`Groman discloses administering a single dosage unit of at least about 0.6
`grams of elemental iron in about 15 minutes or less, as required by claim 1.
`Nor has Petitioner explained why it would have been obvious for one of
`ordinary skill in the art to choose, from all the variables disclosed in
`Groman, those parameters that would result in administering at least about
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