UNITED STATES PATENT AND TRADEMARK OFFICE
`
`
`
`
`
`
`
`
`
`
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`
`
`
`
`
`
`
`
`
`
`PHARMACOSMOS A/S,
`Petitioner,
`
`v.
`
`LUITPOLD PHARMACEUTICALS, INC.,
`Patent Owner.
`
`
`
`
`
`
`
`
`IPR2015-01493; Patent 8,431,549 B2
`
`
`
`
`
`
`
`
`
`
`
`PETITIONER’S OPPOSITION
`TO PATENT OWNER’S MOTION TO AMEND
`
`
`
`
`
`
`
`
`Active 26171364.1
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`
`
`
`
`
`
`
`
`
`
`PHARMACOSMOS A/S,
`Petitioner,
`
`v.
`
`LUITPOLD PHARMACEUTICALS, INC.,
`Patent Owner.
`
`
`
`
`
`
`
`
`IPR2015-01493; Patent 8,431,549 B2
`
`
`
`
`
`
`
`
`
`
`
`PETITIONER’S OPPOSITION
`TO PATENT OWNER’S MOTION TO AMEND
`
`
`
`
`
`
`
`
`Active 26171364.1
`
`
`
`
`
`IPR2015-01493
`
`
`
`TABLE OF CONTENTS
`
`I.
`
`INTRODUCTION ............................................................................................. 1
`
`II. BACKGROUND ............................................................................................... 2
`
`III. ARGUMENT ..................................................................................................... 2
`
`A. The Substitute Claims Are Indefinite ............................................................... 2
`
`1.
`
`2.
`
`3.
`
`“Substantially Non-Immunogenic Carbohydrate” ..................................... 3
`
`“Polyisomaltose” ........................................................................................ 5
`
`“Substantially No Cross-Reactivity With Anti-Dextran Antibodies” ....... 8
`
`B. The Amended Claims Are Not Enabled or Adequately Described .................... 9
`
`1. The Recited Species Of Iron Carbohydrate ............................................... 9
`
`2. Any Subject/Any Route ........................................................................... 13
`
`C. The Amended Claims Lack Novelty Over Groman ......................................... 15
`
`D. Substitute Claim 31 Is Obvious Over Groman ................................................. 18
`
`E. Patent Owner Has Not Distinguished Restless Legs Syndrome Art ................ 18
`
`F. Patent Owner Has Not Distinguished Dextran-Related Art ............................. 21
`
`IV. CONCLUSION ................................................................................................ 24
`
`
`
`
`
`Active 26171364.1
`
`i
`
`
`
`IPR2015-01493
`
`
`
`EXHIBITS RELIED UPON
`
`Exhibit No.
`1001
`1003
`1005
`1006
`1011
`
`1013
`1014
`1019
`1020
`
`1022
`1026
`1028
`1035
`1037
`1038
`1045
`
`Description
`United States (U.S.) Patent No. 8,431,549 (“the ‘549 patent”)
`U.S. Patent Appln. Publication No. 2003/0232084 (“Groman”)
`Marchasin, 1964, Blood 23:354-358 (“Marchasin”)
`Prosecution history of the ‘549 patent
`Declaration Under 37 C.F.R. 1.132 of Richard Lawrence (“the
`Lawrence Declaration”)
`Spinowitz et al., 2005, Kidney Int’l. 68:1801-1807 (“Spinowitz”)
`Declaration of Robert Linhardt
`F.D.A. Orange Book Listing for Injectafer® injection
`F.D.A. Advisory Committee Briefing Document on NDS-22-054
`for Injectafer®, February 1, 2008
`Patent Term Extension Application for the ‘109 patent
`Jahn et al. 2011, Eur. J. Pharma and Biopharma 78:480-91 (“Jahn”)
`European Pharmacopeia for Dextran 1 (2005)
`Neiser, 24 March 2015, Biometals 1-21 (“Neiser 2015”)
`United States Pharmacopeia for Dextran 1 (USP 28:2005)
`Product documentation for Dextran T1
`Neiser et al., 2011, Port. J. Nephrol. Hypert. 25(3):219-224
`(“Neiser”)
`Dr. Adriana Manzi Deposition Transcript
`1054
`1055 Wang et al., JAMA. 314(19):2062-2068 (2015) (“Wang”)
`1056 Wang et al., JAMA. 314(19):2062-2068 (2015), Supplementary
`Content (“Wang Supplementary Content”)
`Charles River monograph for C57BL/6 mice
`1060
`1061 Webpage for the San Diego zoo
`1062
`Egeli et al., 1999, Res. Vet. Sci. 66(3):179-184
`1063
`Document regarding Imferon®’s Recall
`1065
`Prosecution history of the U.S. Application No. 14/683,415
`1067
`Geisser et al. Drug. Red. 41(1):32-37 (1991) (“Geisser 1991”)
`1068
`Anaemex® Certificate of Analysis
`1069
`Presentation from the Galenica Group
`2012
`Fishbane, Am. J. Kidney Dis. 41(5 Suppl):18-26 (2003)
`(“Fishbane”)
`U.S. Patent No. 6,960,571 (“the ‘571 patent”)
`2039
`Declaration of Dr. Adriana Manzi
`2080
`2081 Walters et al. Nephrol. Dial. Transplant 20:1438–1442 (2005)
`
`Active 26171364.1
`
`ii
`
`
`
`IPR2015-01493
`
`
`
`2123
`
`
`
`(“Walters”)
`Dextran and Related Polysaccharides from Sigma-Aldrich (used in
`Linhardt deposition Ex. 2023)
`
`
`Active 26171364.1
`
`iii
`
`
`
`IPR2015-01493
`
`
`
`I.
`
`
`
`INTRODUCTION
`
`Patent Owner has failed to meet its burden of proving that its proposed
`
`substitute claims are patentable. Importantly, Patent Owner has not followed the
`
`Board’s directive to establish, under controlling precedent, how the substitute
`
`claims find support and why such claims are patentable over the prior art. Instead,
`
`Patent Owner has chosen to propose overbroad and fatally indefinite claims which
`
`are neither enabled nor adequately described.
`
`Regarding patentability over the prior art, certain proposed substitute claims
`
`are anticipated or rendered obvious by Groman (Ex. 1003). Patent Owner has
`
`failed to explain - or even consider in its Motion - why the substitute claims would
`
`not be anticipated by Groman for the reasons set forth in Ground 4 of the Petition.
`
`In addition, the proposed claims are unpatentable over prior art relating to Restless
`
`Legs Syndrome and/or iron dextran which Patent Owner identified in its Motion
`
`but failed to distinguish.
`
`But even if they could be considered free of prior art (and they cannot), the
`
`substitute claims trample upon the exacting requirements of 35 U.S.C. § 112. The
`
`proposed claims use indefinite language and would encompass any species (so
`
`there is no frame of reference for “high dose”), any route, and employ agents
`
`disparaged as prior art by the specification, without any guidance how to improve
`
`upon them.
`
`Active 26171364.1
`
`1
`
`
`
`IPR2015-01493
`
`
`
`Accordingly, no amendment or substitution of the claims should be allowed.
`
`II. BACKGROUND
`
`Patent Owner has filed a Motion
`
`to Amend (“Motion”), seeking
`
`conditionally to amend claims challenged in this IPR such that if claims fall under
`
`Ground 2 or 3 of the Petition, they would be replaced by one or more of proposed
`
`substitute claims 24-33. The Board granted permission to file such Motion in an
`
`Order dated March 11, 2016 (Paper 22, “Order”). In the Order, the Board
`
`reminded Patent Owner that it “has the burden of proof to establish that it is
`
`entitled to the requested relief.” Order, 2, citing 37 C.F.R. § 42.20(c). The Board
`
`further explained that Patent Owner “is required to explain why the claims are
`
`patentable over the prior art of record” (citing Microsoft Corp. v. Proxycom, Inc.,
`
`789 F.3d 1292, 1307-1308 (Fed. Cir. 2015)) and directed Patent Owner “that it
`
`should point to where written description support occurs in the originally filed
`
`disclosure for any proposed substitute claim as a whole” (emphasis in original) and
`
`“must point out and discuss how the proposed substitute claims are supported by
`
`the originally filed disclosure in the body of the motion.” Order, 2, 4.
`
`
`
`Patent Owner’s Motion should be denied.
`
`III. ARGUMENT
`
`
`
`For the reasons explained below, the substitute claims, amended as proposed
`
`by Patent Owner, are not patentable.
`
`
`
`A. The Substitute Claims Are Indefinite
`
`Active 26171364.1
`
`2
`
`
`
`IPR2015-01493
`
`
`
`
`
`According to 35 U.S.C. §112, second paragraph (pre-America Invents Act),
`
`“[t]he specification shall conclude with one or more claims particularly pointing
`
`out and distinctly claiming the subject matter which the applicant regards as his
`
`invention.” The substitute claims do not comply with this requirement.
`
`
`
`1.
`
`“Substantially Non-Immunogenic Carbohydrate”
`
`The specification provides no clear boundaries for the meaning of
`
`“substantially non-immunogenic carbohydrate component.” In order to compare
`
`the claims with the prior art, it has been necessary, in this IPR, for Petitioner to
`
`construe this term. Petitioner has posited, and the Board has preliminarily agreed
`
`that the term only requires an assessment of the immunogenicity of the
`
`carbohydrate component. Petition, 20; Decision, 6-7. The Board further remarked
`
`that the specification highlights the relationship between anaphylactoid reactions
`
`and antibodies toward the dextran moiety and, therefore, suggests “obtaining a
`
`carbohydrate component that can overcome these deficiencies associated with a
`
`dextran moiety,” so
`
`that a “substantially non-immunogenic carbohydrate
`
`component” would be a carbohydrate component resulting in a “low risk of
`
`anaphylactoid/hypersensitivity reactions,” implicitly less than prior art dextran.
`
`Decision, 6-7.
`
`In its Response to the Petition, Patent Owner has pointed out that it is not
`
`clear what “low risk” means and has argued that a POSITA would understand that
`
`Active 26171364.1
`
`3
`
`
`
`IPR2015-01493
`
`
`
`a “low risk” of adverse events would be less than 0.6/0.7%. Response, 6. On the
`
`first point, Petitioner agrees that the definition of “low risk” is unclear, but that
`
`lack of clarity stems from the deficient specification of the ‘549 patent. As to the
`
`second point that an arbitrary threshold should be set, Petitioner disagrees and
`
`finds Patent Owner’s conclusion to be improperly based on adverse events caused
`
`by the complex as a whole and, in any case, unsupported by the specification.
`
`Patent Owner improperly looks outside the specification to arrive at this arbitrary
`
`numerical value, consulting one reference cited in the specification (Fishbane, Ex.
`
`2012) and another which is not (Walters, Ex. 2081). That Patent Owner should
`
`need to look so far to find support illustrates the deficiency in the specification.
`
`Patent Owner’s expert, Dr. Manzi, confirmed that the specification does not define
`
`“substantially non-immunogenic” and “does not provide the value of the
`
`percentage of drug-related adverse events that occur upon administration of the
`
`carbohydrate component of any of the iron carbohydrate complexes” disclosed.
`
`Ex. 1054, 51:8-21, 63:13-18.
`
`Moreover, Patent Owner’s proposed claims run afoul of its own intrinsic
`
`record. While the ‘549 Patent is silent on defining low risk, it highlights risk
`
`associated with dextran. Ignoring its own embattlement of dextran, Patent Owner
`
`inappropriately proposes claims encompassing iron polyisomaltose without
`
`excluding the possibility of reactivity with anti-dextran antibodies. Note that, with
`
`Active 26171364.1
`
`4
`
`
`
`IPR2015-01493
`
`
`
`regard to the iron carbohydrate complex as a whole, requiring “substantially no
`
`cross-reactivity with anti-dextran antibodies” is reserved for dependent claim 2.
`
`By claim differentiation, complexes according to claim 1 can have substantial
`
`cross-reactivity with anti-dextran antibodies. This muddies the unclear boundaries
`
`of “substantially non-immunogenic carbohydrate” even further.
`
`Because
`
`the metes and bounds of “substantially non-immunogenic
`
`carbohydrate component” are indefinite, all claims encompassing this term are
`
`indefinite and invalid under 35 U.S.C. § 112 and should be cancelled or refused,
`
`including claims 1-5, 9, 12-16, and 19, currently challenged in this proceeding, as
`
`well as Patent Owner’s proposed substitute claims 24-33. Petitioner further
`
`requests that claims not hitherto challenged in this IPR but which encompass or
`
`recite “substantially non-immunogenic carbohydrate component,” namely issued
`
`claims 6-8, 10, 11, 17, 18, and 20-23, be declared indefinite and invalid and be
`
`cancelled.
`
`
`
`2.
`
`“Polyisomaltose”
`
`After demonizing dextran in its background section, the ‘549 patent
`
`specification shamelessly lists “iron polyisomaltose (iron dextran)” among
`
`complexes useful according to the invention.1 Petition, 15, citing Ex. 1001, 10:43-
`
`
`1 Of note, the specification of a continuation application of the ‘549 patent, U.S.
`
`Patent Application No. 14/683,415, has been altered to remove the language “(iron
`
`Active 26171364.1
`
`5
`
`
`
`IPR2015-01493
`
`
`
`54. Based on this recitation, and certain usage in the art, Petitioner argued that
`
`“the terms ‘polyisomaltose’ and ‘dextran’ should be construed to both refer to
`
`large or small, branched, or unbranched polymers of glucose, provided that they
`
`are linked primarily by α-1-6 glycosidic linkages.” Petition, 16. This Board
`
`stated, in reference to a relative of the ‘549 patent, that negative statements in the
`
`specification regarding early iron dextran products would implicitly exempt those
`
`products from the scope of “iron polyisomaltose complex.” Decision (Paper 11),
`
`Case IPR2015-01495, January 8, 2016, 14 and 12.
`
`While the position of the Board is well taken, assuming there is some
`
`threshold between a purportedly dangerous dextran and allegedly safe
`
`polyisomaltose, the specification provides no guidance where it lies, and “there are
`
`commonly cited examples [in the art] where highly processed, essentially purely
`
`linear molecules of low molecular weight are referred to, in standard terminology,
`
`as ‘dextran,’” two examples being the low molecular weight, essentially purely
`
`linear pharmaceutical compound Dextran 1 and its technical grade counterpart,
`
`Dextran T1. See Petition, 21. Dextran 1 and Dextran T1 are essentially purely
`
`linear glucose polymers having average molecular weights of 1000 Da and almost
`
`exclusively α-1-6 linkages. Ex. 1014, ¶¶10-11; Ex. 1028; Ex. 1037; Ex. 1038.
`
`
`dextran),” without alerting the USPTO that an amendment has been made. Ex.
`
`1065.
`
`Active 26171364.1
`
`6
`
`
`
`IPR2015-01493
`
`
`
`Dextran 1 is well known in the art, having been used as prophylaxis against
`
`anaphylactic reactions to higher molecular weight dextran decades ago and still
`
`referenced to the present day. Petition, 10-11; Ex. 1014, ¶14; Ex. 1011, ¶5. See
`
`also Ex. 2123, cited by Patent Owner, 1, 3.
`
`Any differentiation by Patent Owner between polyisomaltose and dextran
`
`was made without support in the specification, which makes no reference to
`
`linearity, branching, molecular weight, or degree of immunogenicity. Petition, 15-
`
`17. Usage of these terms in the art varies, so that without guidance, a clear
`
`boundary between polyisomaltose and dextran cannot be drawn. Id. In its Motion,
`
`Patent Owner states that “dextran refers to a branched molecule” and has made no
`
`response to Petitioner’s Ground 4 which points out that Dextran T1, used by
`
`Groman, is an essentially purely linear molecule (meaning that virtually all
`
`molecules in a commercial preparation of Dextran T1 are linear). Motion, 4. See
`
`also Ex. 1014, ¶11. Dr. Manzi states that Groman does not disclose that the
`
`technical grade dextrans used in the iron carbohydrate complexes are “processed to
`
`remove branching.” Ex. 2080, ¶77. However, as indicated by Petitioner’s expert,
`
`Dr. Linhardt, when native dextran is treated to prepare low molecular weight
`
`dextrans, “debranching occurs preferentially, leaving behind an increasingly linear
`
`molecule,” indicating that her statement has no merit. Ex. 1014, ¶10. Linearity is
`
`not referenced
`
`in
`
`the specification as a discriminating factor between
`
`Active 26171364.1
`
`7
`
`
`
`IPR2015-01493
`
`
`
`polyisomaltose and dextran, and Patent Owner has failed to show that it was a
`
`guidepost used in the art.
`
`Furthermore, as “hydrogenated dextran”
`
`is
`
`listed separately
`
`in
`
`the
`
`specification, was surrendered during prosecution, and precise usage of
`
`“polyisomaltose” would not include a hydrogenated (i.e., reduced) polyisomaltose
`
`(properly termed “polyisomaltoside”), the term “polyisomaltose” should not
`
`include hydrogenated/reduced polyisomaltose. Petition, 16-17. Yet, Patent
`
`Owner, in the prosecution history, states otherwise. Id.
`
`Because the metes and bounds of “polyisomaltose” are indefinite, all claims
`
`encompassing polyisomaltose are indefinite and invalid under 35 U.S.C. § 112 and
`
`should be cancelled or refused, including claims 1-5, 9, 14-16, and 19, currently
`
`challenged in this proceeding, as well as Patent Owner’s proposed substitute
`
`claims 24-33. Petitioner further requests that claims not hitherto challenged in this
`
`IPR but which encompass or recite “polyisomaltose,” namely issued claims 6-8,
`
`10, 11, 17, 18, and 21, be declared indefinite and invalid and be cancelled.
`
`
`
`3.
`
`“Substantially No Cross-Reactivity With Anti-Dextran
`
`Antibodies”
`
`
`
`Similarly, no guidance is provided as to what constitutes “substantially no
`
`cross-reactivity with anti-dextran antibodies.” While complexes between iron and
`
`carbohydrates other than dextran may be reasonably considered to meet this
`
`Active 26171364.1
`
`8
`
`
`
`IPR2015-01493
`
`
`
`limitation, because claim 2 and substitute claim 25 use the term “substantially”
`
`without further guidance, it is impossible to determine how much cross-reactivity
`
`would be permitted. Patent Owner could have used a more definite term, such as
`
`“essentially no cross-reactivity,” but chose not to.
`
`
`
`Because the meets and bounds of “substantially no cross-reactivity with anti-
`
`dextran antibodies” are unclear, claim 2 and substitute claim 25 are indefinite and
`
`invalid under 35 U.S.C. § 112 and should be cancelled or refused.
`
`
`
`
`
`B.
`
`The Amended Claims Are Not Enabled or Adequately Described
`
`According to 35 U.S.C. § 112, first paragraph (pre-America Invents Act),
`
`“[t]he specification shall contain a written description of the invention, and of the
`
`manner and process of making and using it, in such full, clear, concise, and exact
`
`terms as to enable any person skilled in the art to which it pertains, or with which it
`
`is most nearly connected, to make and use the same, and shall set forth the best
`
`mode contemplated by the inventor of carrying out his invention.” The substitute
`
`claims do not meet this standard.
`
`
`
`
`
`
`
`The Recited Species Of Iron Carbohydrate
`1.
`Polyisomaltose is the species Patent Owner initially elected to pursue2
`
`during the prosecution of the application that became the ‘549 patent. Ex. 1006,
`
`129. Claims covering polyisomaltose were subsequently rejected as lacking
`
`
`2 In response to a restriction requirement, which was later removed.
`
`Active 26171364.1
`
`9
`
`
`
`IPR2015-01493
`
`
`
`enablement, the Examiner questioning how polyisomaltose could be substantially
`
`non-immunogenic and substantially unreactive with anti-dextran antibodies. Id.,
`
`103-106. Patent Owner responded with the Lawrence Declaration citing Monofer®
`
`as an example of an iron complex containing non-immunogenic polyisomaltose.
`
`Yet the specification neither enables nor describes Monofer®, which is iron
`
`complexed with “a pure linear chemical structure of repeating α1-6 linked glucose
`
`units with an average size of 5.2 glucose units and an average molecular weight of
`
`1000 Da,” and has been referred to as “dextran 1-based” and “a reduced Dextran
`
`1000.”3 Ex. 1011, ¶4; Ex. 1026, 2; Ex. 1045, Abstract; Ex. 1035, Abstract.
`
`Monofer® is a parenteral iron carbohydrate complex preparation developed by
`
`Petitioner4 (Petition, 9); nowhere does the specification provide guidance to a
`
`POSITA to prepare and use an iron complex with Monofer®’s characteristics,
`
`including not only its carbohydrate component but also the iron carbohydrate
`
`complex as a whole. Yet according to the Lawrence Declaration, Patent Owner
`
`
`3 Dextran 1000 is dextran having a molecular weight of 1000, i.e., Dextran 1. Ex.
`
`2123. See also Ex. 1028; Ex. 1037; Ex. 1038.
`
`4 Monofer® is the trade name for iron isomaltoside 1000, which reflects its low
`
`molecular weight carbohydrate component and that the carbohydrate is reduced. In
`
`his Declaration, Dr. Linhardt characterizes Monofer® as a “reduced (i.e.,
`
`hydrogenated) oligoisomaltose” or “oligoisomaltoside.” Ex. 1014, ¶13.
`
`Active 26171364.1
`
`10
`
`
`
`IPR2015-01493
`
`
`
`should benefit from the “[p]hysiochemical properties” of Monofer®. Ex. 1011, ¶4.
`
`Nor does the specification describe how other types of polyisomaltose could be
`
`incorporated into complexes with iron and used in methods of treatment at the
`
`recited single unit doses.
`
`The Examiner, in Reasons for Allowance, relied on the Lawrence
`
`Declaration and its mention of prior use of “isomaltose oligomers” to block
`
`anaphylaxis as evidence of enablement of polyisomaltose in the claims. Ex. 1006,
`
`24. Petitioner respectfully disagrees with this conclusion because prior use of
`
`these uncomplexed molecules
`
`(whether
`
`termed
`
`isomaltose oligomers,
`
`polyisomaltose or Dextran 1), combined with the (lack of) teaching of the
`
`specification, does not enable incorporating the reduced (i.e., hydrogenated)
`
`polyisomaltose/Dextran 1 into iron complexes or using those complexes toward
`
`effectively treating patients. The claims pertain not to the compositions
`
`themselves, but to methods of treatment, making the lack of disclosure even more
`
`glaring.
`
`
`
`Likewise, the proposed substitute claims seek to cover use of iron mannitol,
`
`iron gluconate, and iron sorbitol, all compounds known in the art. If these
`
`compounds, and iron polyisomaltose, were not previously administered at higher
`
`single unit dosages according to the claims - at least about 0.6 grams (claim
`
`1/substitute claim 24), at least about 1.0 grams (claim 7), at least about 1.5 grams
`
`Active 26171364.1
`
`11
`
`
`
`IPR2015-01493
`
`
`
`(claim 8), and greater than 1.0 grams (claim 19/substitute claim 32) - what has
`
`changed that now they can be administered this way? The specification offers no
`
`explanation of what needs to be done to make these compounds safe at higher
`
`single unit dosages. Petition, 7. To the contrary, the only shred of guidance
`
`provided in the specification relates to the subject of its sole working example, the
`
`iron carboxymaltose VIT-45, which, itself inadequately described, is not
`
`encompassed by the ‘549 patent claims. To use any of these other, claimed iron
`
`carbohydrate species, a POSITA would need to perform undue experimentation in
`
`an unpredictable art. In re Wands, 858 F.2d 731 (Fed. Cir. 1988).
`
`
`
`Furthermore, there is no written description of embodiments utilizing iron
`
`complexed with particular species of polyisomaltose, mannitol, gluconate, and/or
`
`sorbitol that are exemplary of what the specification intends to be “substantially
`
`non-immunogenic.” There is no evidence that, on the effective filing date of the
`
`‘549 patent, Patent Owner was in possession of such subject matter. To the
`
`contrary, during prosecution of the ‘549 patent, when pressed for an example of a
`
`substantially non-immunogenic polyisomaltose, Patent Owner offered nothing
`
`from its own patent specification but rather looked to Monofer®, which was not
`
`commercially approved until 3 years after the effective filing date of the ‘549
`
`patent and, thus, presumably inaccessible to a POSITA on the critical date.
`
`Petition, 9.
`
`Active 26171364.1
`
`12
`
`
`
`IPR2015-01493
`
`
`
`Accordingly, claims encompassing methods of using iron polyisomaltose,
`
`iron mannitol, iron gluconate, and iron sorbitol fail to meet the enablement and
`
`written description requirements of 35 U.S.C. § 112 and should be cancelled or
`
`refused, including claims 1-5, 9, 14-16, and 19, currently challenged in this
`
`proceeding, as well as Patent Owner’s proposed substitute claims 24-33. Petitioner
`
`further requests that claims not challenged in this IPR proceeding but which
`
`encompass use of these iron complexes, namely issued claims 6-8, 10, 11, 17, 18,
`
`and 20-23 be declared unenabled, lacking written description, and invalid, and be
`
`cancelled.
`
`
`
`
`
`2.
`
`Any Subject/Any Route
`
`Although the working example of the ‘549 patent and all the prior art cited
`
`in this IPR relates to parenteral use of iron, it is notable that only claims 15 and 16
`
`are limited to parenteral usage. It follows that the remaining claims encompass
`
`administration by other routes.5 Patent Owner has failed to explain how any of the
`
`compounds used in the other claims could be used via any means of administration
`
`whatsoever.
`
`
`
`Further, none of the claims specify the species of subject being treated,
`
`
`5 “Any route of delivery of the single unit dose of iron carbohydrate complex is
`
`acceptable so long as iron from the iron complex is released such that symptoms
`
`are treated.” Ex. 1001, 6:48-50.
`
`Active 26171364.1
`
`13
`
`
`
`IPR2015-01493
`
`
`
`literally encompassing mouse to elephant.
`
` Petition, 13.
`
` Logically, the
`
`consequences to a mouse and to an elephant of receiving at least 0.6 grams of iron
`
`as a single unit dose would be very different. The laboratory strain of mouse,
`
`C57BL/6 weights between 20 and 30 grams. Ex. 1060, 4. According to the
`
`website of the San Diego zoo, elephants weigh between 6,000 and 15,000 pounds,
`
`where one pound equals about 453 grams. Ex. 1061, 2. Administering 0.6 grams
`
`of iron to each of these animals would be expected to have very different
`
`consequences. That the claims can reach non-human species is relevant, as
`
`parenteral iron carbohydrate complex supplementation is used in veterinary
`
`medicine.6
`
`Based on the working examples and prior art, the dosages recited in the
`
`claims would have relevance to human subjects but relevance to non-human
`
`subjects is not explored in the specification and there is no direction provided
`
`regarding how to use the disclosed methods in non-human subjects. As none of the
`
`claims are limited to human subjects, all of the claims are unpatentable for lack of
`
`enablement and lack of written description. Claims 1-5, 9, 12-16, and 19 and
`
`proposed substitute claims 24-33, currently challenged in this IPR proceeding, are
`
`therefore invalid for lack of enablement and lack of written description under 35
`
`
`6 Egeli et al., 1999, Res. Vet. Sci. 66(3):179-184 discloses administering 180 mg
`
`elemental iron as iron dextran subcutaneously to day-old piglets. Ex. 1062, 2.
`
`Active 26171364.1
`
`14
`
`
`
`IPR2015-01493
`
`
`
`U.S.C. § 112 and should be cancelled or refused. Petitioner further requests that
`
`remaining issued claims 6-8, 10, 17, 18, and 20-23 be deemed unenabled and
`
`invalid and be cancelled.
`
`
`
`
`
`C.
`
`The Amended Claims Lack Novelty Over Groman
`
`Groman’s teaching of a low molecular weight (1000 Da) essentially purely
`
`linear reduced (i.e., hydrogenated) polyisomaltose, complexed with iron, in
`
`methods of treatment is the basis for Ground 4 of Petitioner’s original challenge.
`
`Groman anticipates the claims currently challenged in this IPR proceeding, namely
`
`claims 1 and 14, as well as proposed substitute claims 24-28, 30, and 33.
`
`
`
`Patent Owner has completely ignored Ground 4 in its Response and Motion
`
`to Amend, despite the fact that claim 14, which invokes base claim 1, has been
`
`declared part of this IPR proceeding. In Ground 4, Petitioner has explained why,
`
`according to Patent Owner’s own words, Groman’s teaching of reduced Dextran
`
`T1 would anticipate claims 14 (and claim 1).
`
`Rather than addressing Ground 4, Patent Owner has purported to distinguish
`
`the substitute claims by the unelaborated statement “Groman … relates to … a
`
`hydrogenated dextran.”7 Motion, 16. Elsewhere, Patent Owner also states that
`
`
`7 During the prosecution of the ‘549 patent, the Examiner required hydrogenated
`
`(i.e., reduced) dextran to be stricken from the claims to secure allowance. Petition,
`
`Active 26171364.1
`
`15
`
`
`
`IPR2015-01493
`
`
`
`“dextran refers to a branched molecule whereas polyisomaltose refers to a linear
`
`molecule.” Motion, 4. But Patent Owner has failed to show how its artificial (and
`
`unsupported) distinction does not apply to the molecules well known as Dextran 1
`
`and Dextran T1. Further, Patent Owner fails to respond to Petitioner’s argument
`
`that Groman uses a (reduced) carbohydrate, which despite being essentially linear,
`
`is called Dextran (Dextran T1) and would fall within the definition of “one
`
`example of a polyisomaltose” called out in the Lawrence Declaration. Ex. 1014,
`
`¶¶10, 11, 16-17. By ignoring to resolve this contradiction, Patent Owner has not
`
`made a prima facie case for the relief requested and fails to meet its burden to
`
`demonstrate the patentability of the claims over the prior art, and particularly art
`
`cited in this IPR proceeding against the claims proposed to be amended. As such,
`
`the proposed amended claims should not be allowed. Idle Free Systems, Inc. v.
`
`Bergstrom, Inc., IPR2012-0027) Decision (Paper 26; June 11, 2013), 37-38.
`
`To summarize Ground 4’s challenge to the claims, the iron carbohydrate
`
`complexes taught by Groman include a carbohydrate that is a reduced Dextran T1,
`
`which has not been further functionalized to include a carboxymethyl group, e.g.,
`
`Ex. 1003, Example 28 (¶¶[0230], [0231]).
`
`Further, Groman discloses that its iron carbohydrate complexes are
`
`
`12. It follows that Patent Owner expressly surrendered all hydrogenated/reduced
`
`dextrans from the scope of the claims. Petition, 16-17.
`
`Active 26171364.1
`
`16
`
`
`
`IPR2015-01493
`
`
`
`“immunosilent” and associated with low risk of anaphylaxis (see, for example, Ex.
`
`1003, ¶[0324] and Table 15) and may be administered as a treatment for anemia as
`
`a single dose of up to 600 mg elemental iron. Id., ¶¶[0004], [0009], [0016],
`
`[0082], [0104]. Groman, therefore, discloses all the limitations of claim 1 and
`
`substitute claim 24, claim 3 and substitute claim 26 (treating anemia), claim 4 and
`
`substitute claim 27 (treating iron deficiency anemia), and claim 5 and substitute
`
`claim 28 (treating anemia of chronic disease). See also Ex. 1014, ¶18.
`
`Claim 14 and substitute claim 33 depend from claims 1 and 24, respectively,
`
`and further require that the iron carbohydrate complex has a mean particle size no
`
`greater than 35 nm or has a mean iron core size that is at least 1 nm but no greater
`
`than about 9 nm. As shown in Table 8 of Groman, iron carbohydrate complexes
`
`generated with reduced Dextran T1 have a mean volume diameter (MVD) of 18
`
`nm, which is less than 35 nm. Ex. 1003, ¶¶[0230-231], Table 8; Ex. 1014, ¶24.
`
`MVD as disclosed in Groman is equivalent to the “mean size of a particle” or
`
`“mean diameter particle size” as disclosed in the ‘549 patent. Ex. 1001, 11:27, Ex.
`
`1014, ¶24.
`
`
`
`Further, Groman discloses parenteral administration of its compositions,
`
`and, therefore, would anticipate claim 15 and its substitute claim 30. Ex. 1003,
`
`¶[0004].
`
`For all the foregoing reasons, Groman anticipates at least claims 1 and 14
`
`Active 26171364.1
`
`17
`
`
`
`IPR2015-01493
`
`
`
`pursuant to Ground 4, and also proposed substitute claims 24, 26, 27, 28, 30, and
`
`33. Accordingly, these claims are invalid under 35 U.S.C. §102(b) and should be
`
`cancelled or refused. Petitioner further requests that claims not hitherto challenged
`
`in this IPR proceeding but which otherwise are anticipated by Groman, including
`
`claim 21, dependent on claim 1 and directed to the species polyisomaltose, be
`
`declared anticipated by Groman and be cancelled.
`
`
`
`D.
`
`Substitute Claim 31 Is Obvious Over Groman
`
`Proposed substitute claim 31 recites 500 mg of elemental iron in less than
`
`about 10 ml of diluent. Groman teaches about 50 to about 600 mg of elemental
`
`iron administered in a single dose, and a volume of between about 1 and about 15
`
`ml, with concentration dependent on body weight. Ex. 1003, ¶[0016]. Groman
`
`also teaches parenteral administration. Id., ¶[0004]. Body weight not being a
`
`component of the instant claims, this disclosure would render obvious the
`
`parenteral administration of 500 mg elemental iron in less than 10 ml diluent
`
`according to substitute claim 31. Accordingly, substitute claim 31 is obvious over
`
`Groman pursuant to 35 U.S.C. §103 and should be held invalid and refused.
`
`
`
`E.
`
`Patent Owner Has Not Distinguished Restless Legs Syndrome Art
`
`In its Motion, Patent Owner identifies United States Patent No. 6,960,571
`
`(Ex. 2039; “the ‘571 patent”) but purports to distinguish it from the substitute
`
`claims, pointing out that Restless Legs Syndrome (“RLS”) has been carved out in
Accessing this document will incur an additional charge of $.
After purchase, you can access this document again without charge.
Accept $ Charge
Still Working On It
This document is taking longer than usual to download. This can happen if we need to contact the court directly to obtain the document and their servers are running slowly.
Give it another minute or two to complete, and then try the refresh button.
A few More Minutes ... Still Working
It can take up to 5 minutes for us to download a document if the court servers are running slowly.
Thank you for your continued patience.
This document could not be displayed.
We could not find this document within its docket. Please go back to the docket page and check the link. If that does not work, go back to the docket and refresh it to pull the newest information.
Your account does not support viewing this document.
You need a Paid Account to view this document. Click here to change your account type.
Your account does not support viewing this document.
Set your membership
status to view this document.
With a Docket Alarm membership, you'll
get a whole lot more, including:
- Up-to-date information for this case.
- Email alerts whenever there is an update.
- Full text search for other cases.
- Get email alerts whenever a new case matches your search.
One Moment Please
The filing “” is large (MB) and is being downloaded.
Please refresh this page in a few minutes to see if the filing has been downloaded. The filing will also be emailed to you when the download completes.
Your document is on its way!
If you do not receive the document in five minutes, contact support at support@docketalarm.com.
Sealed Document
We are unable to display this document, it may be under a court ordered seal.
If you have proper credentials to access the file, you may proceed directly to the court's system using your government issued username and password.
Access Government Site
