UNITED STATES PATENT AND TRADEMARK OFFICE
`_______________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`_____________
`
`
`
`PHARMACOSMOS A/S,
`Petitioner,
`
`v.
`
`LUITPOLD PHARMACEUTICALS, INC.,
`Patent Owner.
`
`
`
`_______________
`
`IPR2015-01490; Patent 7,754,702 B2
`
`____________________________________________________________
`
`PATENT OWNER RESPONSE
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`4845-5485-3167.5
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`IPR2015-01490
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`Patent Owner Response
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`TABLE OF CONTENTS
`
`I. 
`
`II. 
`
`INTRODUCTION ........................................................................................... 1 
`
`BACKGROUND ............................................................................................. 2 
`
`III. 
`
`SUMMARY OF ARGUMENT ....................................................................... 3 
`
`IV.  PERSON OF ORDINARY SKILL IN THE ART .......................................... 4 
`
`V. 
`
`CLAIM CONSTRUCTION ............................................................................ 5 
`
`A. 
`
`“substantially non-immunogenic carbohydrate component” ................ 6 
`
`1.
` 
`
`2.
` 
`
`“substantially non-immunogenic” requires an incidence
`of adverse events lower than iron dextran .................................. 7 
`
`Determination of “substantially non-immunogenic
`carbohydrate component” requires a large enough cohort ......... 9 
`
`B. 
`
`“iron sorbitol complex” does not include “iron polyglucose
`sorbitol carboxymethyl ether complex” .............................................. 10 
`
`C. 
`
`“iron carboxymaltose complex” .......................................................... 14 
`
`VI.  GROUND 1 – Claims 1-3, 10-13, 23, 25, 27, and 41-43 are not
`anticipated by Geisser .................................................................................... 15 
`
`A. 
`
`B. 
`
`Petitioner Has Not Met Its Burden to Demonstrate that Geisser
`Teaches Every Element of Claims 1, 2, 3, 10, 11, 12, 13, 23, 25,
`27, 41, 42, or 43. .................................................................................. 15 
`
`Petitioner has not demonstrated that Geisser inherently
`discloses the claimed “substantially non-immunogenic
`carbohydrate component” ................................................................... 17 
`
`VII.  GROUND 2 – Claim 28 is not anticipated by Groman. ................................ 18 
`
`A.  Groman Does Not Anticipate Claim 1 or Claim 28 ............................ 18 
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`B. 
`
`Groman Does Not Teach Administration of “a single dosage
`unit of at least about 0.6 grams of elemental iron” ............................. 20 
`
`VIII.  GROUND 3 – Claims 17 and 47 are not rendered obvious by the
`combination of Geisser and Groman ............................................................. 22 
`
`A.  Geisser and Groman are directed to structurally different iron
`carbohydrate complexes ...................................................................... 22 
`
`B. 
`
`There was no motivation to combine Geisser and Groman and
`the combination offers no reasonable expectation of success ............ 26 
`
`1.
` 
`
`The combination of Geisser and Groman does not teach
`or suggest an administration of the single dosage unit in
`“about 15 minutes or less” recited in claim 17 ......................... 27 
`
`2.
` 
`
`Claim 47 .................................................................................... 28 
`
`IX.  GROUND 4 – Claims 1, 14, and 15 are not anticipated by van Zyl-
`Smit. ............................................................................................................... 29 
`
`A. 
`
`B. 
`
`C. 
`
`van Zyl-Smit does not teach a “substantially non-immunogenic
`carbohydrate component” ................................................................... 29 
`
`van Zyl-Smit’s sample size is not large enough to reveal a
`“substantially non-immunogenic” property ........................................ 31 
`
`The results of van Zyl-Smit are not generalizable to iron
`polymaltose ......................................................................................... 33 
`
`X.  GROUND 5 – Claim 30 is not rendered obvious by the combination
`of van Zyl-Smit and Funk .............................................................................. 35 
`
`A. 
`
`B. 
`
`Petitioner’s conclusions on Funk are incorrect ................................... 35 
`
`There was no motivation to combine van Zyl-Smit and Funk
`and the combination offers no reasonable expectation of
`success. ................................................................................................ 39 
`
`XI.  CONCLUSION .............................................................................................. 40
`
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`TABLE OF AUTHORITIES
`
`
`CASES 
`Atofina v. Great Lakes Chemical Corp., 441 F.3d 991 (Fed. Cir. 2006) ................ 21
`
`Eli Lilly & Co. v.Zenith Goldline Pharms., Inc., 471 F.3d 1369, 1376 (Fed. Cir.
`2006). .................................................................................................................. 16
`
`In re Cuozzo Speed Techs., LLC, 793 F.3d 1268 (Fed. Cir. 2015) ............................ 5
`
`In re Translogic Tech., Inc., 504 F.3d 1249 (Fed. Cir. 2007) ................................... 5
`
`Pfizer, Inc. v. Ranbaxy Labs. Ltd., 457 F.3d 1284, 1290 (Fed. Cir 2006) ............... 13
`
`Pharmacosmos A/S v. Luitpold Pharmaceuticals, Inc., IPR2015-01493, Decision
`Granting Institution, Paper 11, January 8, 2016 ................................................... 7
`
`Pharmacosmos A/S v. Luitpold Pharmaceuticals, Inc., IPR2015-01495, Decision
`Denying Institution (Paper 11) January 8, 2016 ................................................. 23
`
`Phillips v. AWH Corp., 415 F.3d 1303 (Fed. Cir. 2005) ........................................... 5
`
`STATUTES 
`
`21 CFR § 314.53 ...................................................................................................... 16
`
`35 U.S.C. § 112 (pre-AIA) ....................................................................................... 18
`
`35 U.S.C. § 316(a)(8) ................................................................................................. 1
`
`35 U.S.C. 316(e) ........................................................................................................ 1
`
`37 C.F.R. § 42.100(b) ................................................................................................ 5
`
`37 C.F.R. § 42.120 ..................................................................................................... 1
`
`
`
`
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`IPR2015-01490
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`Exhibit No.
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`EXHIBITS RELIED ON
`Description
`
`Patent Owner Response
`
`1001
`
`1003
`
`1004
`
`1005
`
`1006
`
`1011
`
`1017
`
`1021
`
`1022
`
`1023
`
`1026
`
`1035
`
`1042
`
`1048
`
`2003
`
`2012
`
`2015
`
`U.S. Patent No. 7,754,702 (“the ’702 patent”)
`
`Translation of International Patent Publ. No. WO 2004/037865
`(“Geisser”)
`
`U.S. Patent Appl. Publication No. 2003/0232084 (“Groman”)
`
`Declaration of Robert Linhardt
`
`van Zyl-Smit and Halkett, Nephron 92:316-323 (2002)
`(“van Zyl-Smit”)
`
`Spinowitz et al. Kidney Int’l. 68:1801-1807 (2005) (“Spinowitz”)
`
`U.S. Patent No. 6,599,498 (“the ‘498 patent”)
`
`Excerpt of Prosecution History of European Patent Application
`EP1973549
`
`Neiser et al. Port. J. Nephrol. Hypert. 25(3):219-224 (2011)
`(“Neiser”)
`
`British Pharmacopoeia Monograph for Iron Sorbitol (2003)
`
`Funk, et al. Hyperfine Interactions 136:73-95 (2001) (“Funk”)
`
`Neiser et al., Biometals 1-21 (2015)
`
`Excerpts of the File History of U.S. Patent No. 8,895,612
`
`Danielson, Journal of the American Society of Nephrology 15:593-
`598 (2004)
`
`Ferrosig Drug Product Data Sheet, Revised July 2003
`
`Fishbane, Am. J. Kidney Dis. 2003 41(5 Suppl):18-26
`
`Volhardt, Organic Chemistry, W.H. Freeman Co 2007 p. 1096-138
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`2022
`
`2056
`
`2057
`
`2080
`
`2081
`
`2082
`
`2084
`
`2085
`
`Ahsan et al., Adv. Perit. Dial. 1996 12:161-6
`
`Transcript of March 2016 Deposition of Dr. Richard Linhardt
`
`Curriculum vitae of Dr. Adriana Manzi
`
`Declaration of Dr. Adriana Manzi
`
`Walters et al., Nephrol. Dial. Transplant 2005 20:1438–1442
`(“Walters”)
`
`Lindvall, S. and Andersson N. S. E. Brit. J. Pharmacol. 17:358-371
`(1961) (“Lindvall”)
`
`Lam-Po-Tang, et al. Peritoneal Dialysis International Jul-Aug
`23:405-406 (2003)
`
`Sax, N. I. and Lewis, R. J., Hawley’s Condensed Chemical
`Dictionary, Van Nostrand Reinhold Company, Eleventh Ed. (1987),
`p. 797, 1081-1082
`
`2086
`
`Morris, et al. Journal of Supramolecular Structure 6:259-274 (1977)
`
`
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`v
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`IPR2015-01490
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`I.
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`INTRODUCTION
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`Patent Owner Response
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`Pursuant to 35 U.S.C. § 316(a)(8) and 37 C.F.R. § 42.120, Patent Owner
`
`Luitpold Pharmaceuticals, Inc. files this Response to the Petition of Pharmacosmos
`
`A/S challenging claims of U.S. Patent No. 7,754,702 (“the ’702 Patent”).
`
`Luitpold responds to the following five grounds on which the Board instituted inter
`
`partes review:
`
`(1) Ground 1 – alleged anticipation of claims 1-3, 10-13, 23, 25, 27, and 41-43
`
`over WO 2004/037865 (“Geisser,” Ex. 1002, citations to English translation,
`
`provided as Ex. 1003),
`
`(2) Ground 2 – alleged anticipation of claim 28 over US 2003/0232084
`
`(“Groman,” Ex. 1004),
`
`(3) Ground 3 – alleged obviousness of claims 17 and 47 over the combination of
`
`Geisser and Groman,
`
`(4) Ground 4 – alleged anticipation of claims 1, 14, and 15 over van Zyl-Smit (Ex.
`
`1006), and
`
`(5) Ground 5 – alleged obviousness of claim 30 over the combination of van Zyl-
`
`Smit and Funk (Ex. 1026). Paper 11, p. 19.
`
`Petitioner bears “the burden of proving a proposition of unpatentability by a
`
`preponderance of the evidence.” 35 U.S.C. 316(e). For the reasons set forth
`
`below, Petitioner has failed to meet its burden.
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`II. BACKGROUND
`The specification of the ’702 patent details the need in the art for iron
`
`formulations with low health risk that may be administered in high doses. Ex.
`
`2080, ¶9.
`
`In addition to noting the risks associated with iron dextran, the background
`
`section of the specification details that “[a]lthough serious and life-threatening
`
`reactions occur most frequently with iron dextran, they are also known to occur
`
`with other parenteral iron products.” Ex. 1001, col. 1:39-41; Ex. 2080, ¶10.
`
`Moreover, the specification points out that “non-life threatening reactions such as
`
`arthralgia, back pain, hypotension, fever, myalgia, pruritus, vertigo, and vomiting”
`
`can preclude high dosing of known iron formulations. Ex. 1001, col. 1:42-46; Ex.
`
`2080, ¶10.
`
`In discussing further issues with dosing, the specification posits that
`
`“[v]arious pharmacokinetic studies suggest that doses of iron complexes higher
`
`than 200 mg of iron are generally unsuitable and that the conventional therapy
`
`prescribes repeated applications of lower doses over several days. See Geisser et
`
`al., (1992) Arzneimittelforschung 42: 1439-1452.” Ex. 1001, col. 2:9-13; Ex.
`
`2080, ¶11.
`
`As of 2004, for example, commercially available iron carbohydrate
`
`compounds were packaged at doses below 100 mg. Ex. 1048, p. 2.
`2
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`What was needed by January 2006 was a pharmaceutical product that could
`
`be administered at high doses in a relatively short time, and that did not have the
`
`immunogenicity and toxicity of the other products. In order to fulfill the long felt
`
`need in the art, the specification discloses iron carbohydrate complexes along with
`
`methods for high dose administration and rapid rates of administration that
`
`significantly ameliorate adverse reactions, unlike iron dextran. Among the
`
`complexes contemplated in the ’702 patent are iron carboxymaltose complex VIT-
`
`45 and ferumoxytol. VIT-45 is exemplified in the Examples of the ’702 patent.
`
`Ferumoxytol is referred to by both its proprietary and chemical name in the
`
`specification of the’702 patent, and disclosures of ferumoxytol are included by
`
`citation to U.S. Patent No. 6,599,498 (“the ’498 patent,” Ex. 1017) – the parent of
`
`the Groman reference (Ex. 1004) cited by Petitioner (Petition, p. 2).
`
`III. SUMMARY OF ARGUMENT
`Ground 1: Petitioner has not met its burden in demonstrating that Geisser
`
`teaches each and every limitation of the claims. For example, Geisser does not
`
`teach an iron carbohydrate complex having a “substantially non-immunogenic
`
`carbohydrate component.”
`
`Ground 2: Groman does not disclose any of the iron carbohydrate
`
`complexes in independent claim 1 and thus does not anticipate claim 1. Claim 28
`
`depends directly from claim 1. Accordingly, Groman cannot anticipate claim 28.
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`Ground 3 – The combination of Groman and Geisser does not teach each
`
`and every element of claims 17 or 47. Moreover, there is no motivation to
`
`combine Groman and Geisser with a reasonable expectation of success.
`
`Ground 4 –Petitioner has not met its burden to prove that van Zyl-Smit
`
`discloses a substantially non-immunogenic carbohydrate component. van Zyl-Smit
`
`only discloses administration of an iron carbohydrate complex and not the
`
`carbohydrate by itself. Moreover, the sample size of the patient cohort in van Zyl-
`
`Smit is too small to demonstrate that the iron polymaltose is substantially non-
`
`immunogenic.
`
`Ground 5 –The combination of van Zyl-Smit and Funk does not teach each
`
`and every element of claim 30. Moreover, there is no motivation to combine van
`
`Zyl-Smit and Funk with a reasonable expectation of success.
`
`IV. PERSON OF ORDINARY SKILL IN THE ART
`Patent Owner agrees with Petitioner to the extent that a person of ordinary
`
`skill in the art (“POSITA”) for this patent would hold an undergraduate degree in
`
`chemistry or biochemistry with some related academic or industrial experience in
`
`the area of carbohydrates and their metal complexes. Petition, p. 14. Patent
`
`Owner disagrees, however, to the extent that Petitioner’s “at least” treats one with,
`
`say, a Ph.D. as ordinarily skilled just like one with a B.S. Ex. 2080, ¶ 16. Indeed,
`
`Petitioner’s expert Dr. Linhardt stated in his deposition that “some related post-
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`graduate experience” “could be a year or two or three working in an academic or
`
`industrial environment.” Ex. 2056, p. 24, ll. 8-10. Furthermore, since the ’702
`
`patent claims are directed to a method of treatment, “some relevant academic or
`
`industrial experience” requires some experience in either the production of
`
`biologics for pharmaceutical use or the administration of such compounds in the
`
`context of their pharmaceutical use. Ex. 2080, ¶17. Luitpold’s expert Dr. Manzi is
`
`well qualified to opine on the understanding of a POSITA. Ex. 2057.
`
`V. CLAIM CONSTRUCTION
`The claims of a patent must be given their broadest reasonable interpretation
`
`consistent with the specification as it would be understood by one of ordinary skill
`
`in the art. 37 C.F.R. § 42.100(b); see In re Cuozzo Speed Techs., LLC, 793 F.3d
`
`1268, 1278-80 (Fed. Cir. 2015); In re Translogic Tech., Inc., 504 F.3d 1249, 1257
`
`(Fed. Cir. 2007); see also Phillips v. AWH Corp., 415 F.3d 1303, 1316 (Fed. Cir.
`
`2005). Consistent with the law, Patent Owner presents arguments for claim
`
`construction in the context of the specification, prosecution history, and
`
`understanding in the art.
`
`Independent claim 1 recites:
`
`A method of treating a disease, disorder, or condition characterized by
`iron deficiency or dysfunctional iron metabolism resulting in
`reduced bioavailability of dietary iron,
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`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 polymaltose complex, an iron gluconate
`complex, and an iron sorbitol complex; and
`the iron carbohydrate complex has a substantially non-
`immunogenic carbohydrate component and substantially no
`cross reactivity with anti-dextran antibodies
`wherein said disease, disorder or condition is not Restless Leg
`Syndrome.
`
`Ex. 1001, col. 26:49-67.
`
`The Board determined that for the purposes of the Decision instituting trial,
`
`none of the terms in the challenged claims require express construction. Paper 11,
`
`p. 5.
`
`For the purposes of this response, Patent Owner presents the broadest
`
`reasonable interpretation of the following terms.
`
`“substantially non-immunogenic carbohydrate component”
`
`A.
`In a related proceeding for a patent in the same family as the ’702 patent, the
`
`Board construed the term “substantially non-immunogenic carbohydrate
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`component” as a carbohydrate component resulting in a “low risk of
`
`anaphylactoid/hypersensitivity reactions.” Pharmacosmos A/S v. Luitpold
`
`Pharmaceuticals, Inc., IPR2015-01493, Decision Granting Institution, Paper 11,
`
`January 8, 2016, p. 7. However, the Board’s construction of “substantially non-
`
`immunogenic carbohydrate component” as a carbohydrate component resulting in
`
`a “low risk of anaphylactoid/hypersensitivity reactions” does not indicate what
`
`“low risk” means. Ex. 2080, ¶ 21.
`
`
`1.
`
`“substantially non-immunogenic” requires an incidence of
`adverse events lower than iron dextran
`
`Patent Owner presents a construction of the term “substantially non-
`
`immunogenic” as requiring an incidence of adverse events lower than iron dextran.
`
`Ex. 2080, ¶21. The specification disparages iron dextran, stating that iron dextran
`
`“has been associated with an incidence of anphylactoid-type reactions” (Ex. 1001,
`
`col. 1:47-49) and citing Fishbane (Exhibit 2012). Fishbane discloses that “[t]he
`
`risk for immediate severe anaphylactoid reactions appears to be, at a minimum,
`
`approximately 0.6% with IV iron dextran, and this agent has been associated with a
`
`number of deaths during the past several decades.” Ex. 2012, p. 2. Fishbane also
`
`references other studies in which anaphylactoid reactions upon intravenous iron
`
`dextran administration were at levels of 1.8% and 1.7%. Ex. 2012, p. 2; Ex. 2080,
`
`¶21. Other researchers have studied the incidence of adverse reactions to iron
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`dextran and ascertained “the incidence of iron dextran reactions requiring
`
`resuscitative agents to be 0.035%.” Ex. 2081 (“Walters”), p. 1. Walters also found
`
`that “without regard to severity of reaction, [the] overall per patient adverse drug
`
`event (ADE) rate [was] 0.69% (337 out of 48,509) and per exposure rate [was]
`
`0.03% (337 out of 1 066 099).” Ex. 2081, p. 1; Ex. 2080, ¶22. Based on Fishbane
`
`and Walters, a POSITA would understand the overall adverse event incidence rate
`
`for iron dextran is about 0.6-0.7%. Thus, a POSITA would understand
`
`“substantially non-immunogenic” to require an incidence rate lower than that of
`
`iron dextran. Ex. 2080, ¶22.
`
`The specification notes that upon administration of iron carboxymaltose
`
`(VIT-45) (an iron carbohydrate complex recited in claim 1), “[t]he incidence of
`
`drug-related treatment-emergent adverse events of hypersensitivity was 0.2%, the
`
`same as that observed with oral iron (0.2%).” Ex. 1001, col. 26: 12-14.
`
`Accordingly, in light of the specification and the incidence of adverse events in the
`
`references cited therein, the term “substantially non-immunogenic” should mean
`
`an incidence level of adverse events lower than that exhibited by iron dextran, i.e.,
`
`lower than 0.6%. Ex. 2080, ¶22.
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`2.
`
`Determination of “substantially non-immunogenic
`carbohydrate component” requires a large enough cohort
`
`Also, to learn whether that an iron carbohydrate complex has a
`
`“substantially non-immunogenic carbohydrate component” requires administration
`
`to a sample size sufficient to reveal adverse immune effects were they to arise. Ex.
`
`2080, ¶23. In other words, a study’s ability to predict the “low risk” of any effect
`
`associated with administration requires administration to a large enough sample
`
`based on the incidence level of the “risk.” As confirmed by Dr. Linhardt during
`
`his deposition, the appearance of side effects “depends on the frequency of the side
`
`effect and it depends on the agent.” Ex. 2056, p. 96, ll. 21-22.
`
`As of 2006, a POSITA knew that for “[intravenous] iron dextran, the
`
`expected risk for serious anaphylactoid reactions [is] approximately 6/1,000
`
`patients….” Ex. 2012, p. 2; Ex. 2080, ¶24. However, as cautioned in Fishbane,
`
`“the risk is far from negligible, and viewed in the context of a large hemodialysis
`
`practice that treats several hundred patients, it is likely that several severe reactions
`
`will be encountered over the course of time with IV iron dextran.” Ex. 2012, p. 2.
`
`In fact, Spinowitz, a reference identified as evidence of the state of the art by
`
`Petitioner (Petition, pp. 14-16), cautions about the dangers of iron dextran, “which
`
`was recalled by the FDA in 1990.” Ex. 1011, p. 5. Spinowitz also refers to a
`
`cohort size of “almost 2400” from a 1968 review article compiling different iron
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`dextran studies (Wallerstein, Ex. 2014) and characterizes that size as a “relatively
`
`small cohort.” Ex. 1011, p. 5; Ex. 2080, ¶26. One consequence of a small cohort,
`
`says Spinowitz, is that “it is not possible to accurately describe serious adverse
`
`reaction rates.” Ex. 1011, p. 5; Ex. 2080, ¶26. In the same vein and commenting
`
`on his own ferumoxytol study of twenty-one patients (n=21), Spinowitz reports:
`
`“Anaphylaxis and immediate hypotension were not observed in this small study,
`
`but the number of exposures is too small to draw any definitive conclusions.” Ex.
`
`1011, p. 5. That is, even though those adverse events were “not observed,” the
`
`“too small” size of his ferumoxytol cohort precluded “any definitive conclusions.”
`
`Ex. 1011, p. 5; Ex. 2080, ¶26. Thus, Spinowitz (acknowledged as “state of the art”
`
`by Petitioner) recognizes a need for a sample size that is large enough to reveal the
`
`existence of infrequent but serious adverse reactions. Ex. 2080, ¶26.
`
`Thus, Patent Owner proposes a construction of the term “substantially non-
`
`immunogenic carbohydrate component” as a carbohydrate component having an
`
`“incidence rate of anaphylactoid/hypersensitivity reactions lower than that for
`
`dextran, when administered to a cohort large enough to reveal adverse events.”
`
`B.
`
`“iron sorbitol complex” does not include “iron polyglucose
`sorbitol carboxymethyl ether complex”
`
`Claim 1 recites an “iron sorbitol complex.” Ex. 1001, col. 26:61. A
`
`POSITA would understand the term “sorbitol” to be a sugar alcohol having the
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`following structure, as seen in an Organic Chemistry textbook:
`
` (Ex. 2015, p. 18); Ex. 2080, ¶27.
`
`Thus, Patent Owner proposes that the broadest reasonable construction of
`
`“iron sorbitol complex” is “a complex of iron and sorbitol,” with the structure of
`
`sorbitol as depicted above. This interpretation is also supported in the art. See,
`
`e.g., Ex. 2082 (“Lindvall”), titled “Studies on a new Intramuscular Haematinic,
`
`Iron-Sorbitol,” which describes “a complex of iron, sorbitol and citric acid.” Ex.
`
`2080, ¶¶27-28. Thus, the broadest reasonable construction of “iron sorbitol
`
`complex” is “a complex of iron and sorbitol.” Ex. 2080, ¶28.
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`Petitioner argues that a POSITA would understand an “iron sorbitol
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`complex” to “refer to iron complexed with sorbitol monosaccharide.” Petition, p.
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`12. Patent owner disagrees with this construction because “iron sorbitol complex”
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`refers to a complex of iron and sorbitol, and because sorbitol is not a
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`“monosaccharide.” A “monosaccharide” is commonly understood by a POSITA as
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`the monomeric form of a carbohydrate, which has the general formula CnH2nOn.
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`Ex. 2015, pp. 3-4; Ex. 2080, ¶28. In contrast, sorbitol is generally understood by a
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`POSITA to be a sugar alcohol (also known as alditol) that is not part of a polymer.
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`Ex. 2015, pp. 17-18; Ex. 2080, ¶28. Furthermore, Hawley’s Condensed Chemical
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`Dictionary provides a definition of “monosaccharide” as “[a]ny of several simple
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`sugars having the formula C6H12O6” and a chemical formula for sorbitol as
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`“C6H8(OH)6.” Ex. 2085, pp. 3, 4; Ex. 2080, ¶28.
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`Iron sorbitol complex, however, does not encompass iron polyglucose
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`sorbitol carboxymethyl ether complex. Ex. 2080, ¶29. The specification discloses
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`that “[f]erumoxytol is a superparamagnetic iron oxide that is coated with a low
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`molecular weight semi-synthetic carbohydrate, polyglucose sorbitol carboxymethyl
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`ether.” Ex. 1001, col. 13:39-42. In view of the specification, the iron polyglucose
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`sorbitol carboxymethyl ether complex would be understood by a POSITA to mean
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`iron complexed to glucose polymer (“polyglucose”) where the terminal glucose
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`monomer is reduced (“sorbitol”) and carboxymethylated (“carboxymethylether”).
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`Ex. 2080, ¶29. This complex cannot be encompassed by the term “iron sorbitol
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`complex.” Ex. 2080, ¶29.
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`Patent Owner is aware of arguments presented by European counsel during
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`prosecution of the corresponding European application arguing that iron
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`polyglucose sorbitol carboxymethyl ether complex is an iron sorbitol complex. Ex.
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`1021, p. 3. However, these foreign-jurisdiction arguments do not control the
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`construction in the present proceeding. See Pfizer, Inc. v. Ranbaxy Labs. Ltd., 457
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`F.3d 1284, 1290 (Fed. Cir 2006) (“[T]he statements made during prosecution of
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`foreign counterparts to the [patent in suit] are irrelevant to claim construction
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`because they were made in response to patentability requirements unique to Danish
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`and European law.”) Rather, the understanding from the prosecution of a
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`continuing application of the present application should control. Moreover, the
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`arguments in the European prosecution would be understood by a POSITA to be
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`scientifically inaccurate. Ex. 2080, ¶30.
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`Here, arguments and amendments from the prosecution of applications
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`directly related to the present application should control the interpretation of “iron
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`sorbitol complex.” During prosecution of U.S. Pat. No. 8,895,612, which issued
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`from a grandchild application of the ’702 patent, Luitpold separately included iron
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`polyglucose sorbitol carboxymethyl ether complex as a species in the independent
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`claims distinct from iron sorbitol complex. Ex. 1042, p. 17. Patent Owner’s
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`arguments in the response accompanying the claim amendments are also consistent
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`with this interprepatation. Ex. 1042, p. 24 (“ferumoxytol (i.e. an iron polyglucose
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`sorbitol carboxymethyl ether; more specifically, a polyglucose sorbitol
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`carboxymethyl ether-coated non-stoichiometric magnetite) is a preferred complex
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`for use methods of the present disclosure and falls within the scope of claim 1 (see
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`also claims 15-16).”) ; Ex. 2080, ¶31. These amendments and arguments were
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`submitted subsequent to the arguments in the European prosecution and should
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`control the meaning of the term “iron sorbitol complex.” Ex. 2080, ¶31.
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`Thus, based on the common understanding in the art and arguments in a
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`subsequent controlling application, the broadest reasonable interpretation of “iron
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`sorbitol complex” is “a complex of iron and sorbitol.” Ex. 2080, ¶28. Moreover,
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`this interpretation does not include iron polyglucose sorbitol carboxymethyl ether
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`complex. Ex. 2080, ¶29.
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`C.
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` “iron carboxymaltose complex”
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`Petitioner attempts to characterize “iron carboxymaltose complex” merely in
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`terms of its process of making. Petition, p. 11. Patent Owner disagrees with
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`Petitioner’s construction. However, Patent Owner agrees with Petitioner’s expert
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`with regard to his description of carboxymaltose as “a maltose or maltodextrin,
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`comprised of maltose type units, in which the aldehyde group of the reducing sugar
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`end has been oxidized to form a carboxylic acid group. Maltose is a D-
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`glucopyranose dimer linked through an -1-4 glycosidic bond.” Ex. 1005, ¶8; Ex.
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`2080, ¶32. In addition, Patent Owner submits that “iron carboxymaltose complex”
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`must be consistent with the construction of “iron carbohydrate complex,” because
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`iron carboxymaltose complex is a subgenus nested within the “iron carbohydrate
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`complex” genus of claim 1. Ex. 1001, col. 26:58-59; Ex. 2080, ¶32. Thus, the iron
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`carboxymaltose complex must have a “substantially non-immunogenic
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`carbohydrate component.” Ex. 2080, ¶32.
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`VI. GROUND 1 – Claims 1-3, 10-13, 23, 25, 27, and 41-43 are not
`anticipated by Geisser
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`Petitioner has not met its burden of showing that Geisser teaches each and
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`every limitation of claims 1-3, 10-13, 23, 25, 27, and 41-43. Specifically,
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`Petitioner has not demonstrated that Geisser teaches an iron carbohydrate complex
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`having a “substantially non-immunogenic carbohydrate component.” Accordingly,
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`these claims are not anticipated by Geisser.
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`A.
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`Petitioner Has Not Met Its Burden to Demonstrate that Geisser
`Teaches Every Element of Claims 1, 2, 3, 10, 11, 12, 13, 23, 25, 27,
`41, 42, or 43.
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`Petitioner has not met its burden of demonstrating that Geisser discloses
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`each and every element of claims 1, 2, 3, 10, 11, 12, 13, 23, 25, 26, 27, 41, 42, or
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`43. As noted above, iron carboxymaltose complex must be considered as a whole
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`in the context of immune limitations. Ex. 2080, ¶32. Thus, the iron carbohydrate
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`complex must have “a substantially non-immunogenic carbohydrate component”
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`and have “substantially no cross-reactivity with anti-dextran antibodies.” Geisser
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`does not specifically disclose these properties and Petitioner does not argue
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`otherwise. Rather, Petitioner effectively acknowledges this deficiency by arguing
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`that the listing of Geisser in the FDA’s Orange Book for Injectafer® would render
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`it an anticipatory reference. Petition, p. 17. However, in doing so, Petitioner
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`conflates the FDA’s requirements for listing a patent in the Orange Book with the
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`requirements for an anticipatory reference. A patent that can be listed in the
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`Orange Book includes “a patent that claims the drug or a method of using the
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`drug.” 21 CFR § 314.53. Thus, a patent listed in the Orange Book can claim a
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`genus encompassing the species for which FDA approval is sought.
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`Petitioner notes that the U.S. patent equivalent of Geisser is listed in the
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`Food and Drug Administration’s Orange Book for Injectafer®, conflating the
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`standards for listing a patent in the Orange Book and anticipating a claim. Geisser
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`may claim a genus encompassing the iron carboxymaltose species and is thereby
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`sufficient for listing in the Orange Book for Injectafer®. Petitioner, however, does
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`not specifically identify where Geisser’s disclosure is such that the species in claim
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`1 of the ’702 patent would be “at once envisaged” from the disclosure. See Eli
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`Lilly & Co. v.Zenith Goldline Pharms., Inc., 471 F.3d 1369, 1376 (Fed. Cir. 2006).
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`Thus, Petitioner has not met its burden of demonstrating that Geisser
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`necessarily discloses iron carboxymaltose as claimed in claim 1.
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`Petitioner has also not demonstrated that Geisser discloses a “an iron
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`carbohydrate complex with a substantially non-immunogenic carbohydrate
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`component” as required by claim 1. Geisser does disclose that “the preparation to
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`be made available is supposed to demonstrate reduced toxicity and to prevent the
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`dangerous anaphylactic shocks that can be induced by dextran.” Ex. 1003, p. 3 ll.
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`26-28. Geisser also discloses that the “toxicity of the complexes according to the
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`invention is very low