trials@uspto.gov
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`571-272-7822
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`IPR2015-01490, Paper No. 53
`IPR2015-01493, Paper No. 53
`November 3, 2016
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`RECORD OF ORAL HEARING
`UNITED STATES PATENT AND TRADEMARK OFFICE
`- - - - - -
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
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`PHARMACOSMOS A/S
`Petitioner
`vs.
`LUITPOLD PHARMACEUTICALS, INC.
`Patent Owner
`- - - - - -
`Case IPR2015-01490 and IPR2015-01493
`Patent 7,754,702 and 8,431,549
`- - - - - -
`Oral Hearing Held: September 22, 2016
`
`
`Before: TONI R. SCHEINER, LORA M. GREEN and
`CHRISTOPHER G. PAULRAJ, Administrative Patent Judges
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`The above-entitled matter came on for hearing on Thursday,
`September 22, 2016 at the U.S. Patent and Trademark Office, 600 Dulany
`Street, Alexandria, Virginia in Courtroom B, at 1:00 p.m.
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`REPORTED BY: KAREN BRYNTESON, RMR, CRR,
`
`FAPR
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`571-272-7822
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`IPR2015-01490, Paper No. 53
`IPR2015-01493, Paper No. 53
`November 3, 2016
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`
`
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`RECORD OF ORAL HEARING
`UNITED STATES PATENT AND TRADEMARK OFFICE
`- - - - - -
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`- - - - - -
`PHARMACOSMOS A/S
`Petitioner
`vs.
`LUITPOLD PHARMACEUTICALS, INC.
`Patent Owner
`- - - - - -
`Case IPR2015-01490 and IPR2015-01493
`Patent 7,754,702 and 8,431,549
`- - - - - -
`Oral Hearing Held: September 22, 2016
`
`
`Before: TONI R. SCHEINER, LORA M. GREEN and
`CHRISTOPHER G. PAULRAJ, Administrative Patent Judges
`
`The above-entitled matter came on for hearing on Thursday,
`September 22, 2016 at the U.S. Patent and Trademark Office, 600 Dulany
`Street, Alexandria, Virginia in Courtroom B, at 1:00 p.m.
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`REPORTED BY: KAREN BRYNTESON, RMR, CRR,
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`FAPR
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`LISA B. KOLE, ESQ.
`PAUL A. RAGUSA, ESQ.
`JENNIFER C. TEMPESTA, ESQ.
`CAROLYN PIRRAGLIA, ESQ.
`Baker Botts LLP
`30 Rockefeller Plaza
`New York, New York 10112-4498
`212-408-2628
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`ON BEHALF OF THE PATENT OWNER:
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`APPEARANCES:
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`ON BEHALF OF THE PETITIONER:
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`GEORGE E. QUILLIN, ESQ.
`MICHAEL D. KAMINSKI, ESQ.
`ASHA K. NADIPURAM, ESQ.
`NATASHA IYER, ESQ.
`Foley & Lardner LLP
`3000 K Street N.W.
`Washington, D.C. 20007-5109
`202-672-5300
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`P R O C E E D I N G S
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`(1:13 p.m.)
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`JUDGE PAULRAJ: Please be seated.
`Good afternoon. Thanks for your patience as we
`set up the overflow room. This is a hearing in two IPRs,
`IPR2015- 01490 and IPR2015- 01493.
`There is a motion to amend involved in these IPRs.
`And I understand that the parties have conferred regarding the
`order of presentation. And I will read the parties' e-mail into
`the record so that we have that.
`"The parties have conferred and decided that they
`would like to present their arguments as a combined version of
`the sequential option. Petitioner talks first, presenting on its
`two petitions; then Patent Owner presents its response to the
`two petitions and its arguments on its two motions to amend,
`and then Petitioner replies to Patent Owner's responses on the
`two petitions and presents its responses on the two motions to
`amend. And, finally, Patent Owner replies to Petitioner's
`responses on the two motions to amend."
`Let's start with roll call. The Petitioner first.
`MS. KOLE: My name is Lisa Kole, Your Honors,
`here for Pharmacosmos, Petitioner.
`MR. RAGUSA: Paul Ragusa on behalf of
`Petitioner.
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`MR. QUILLIN: I am George Quillin with Foley &
`Lardner, lead counsel for Patent Owner, Luitpold
`Pharmaceuticals. And I have with me my partner Mike
`Kaminski, who will be arguing today, and our colleague Asha
`Nadipuram and hearing remotely, I trust, is our other
`colleague, Natasha Iyer.
`JUDGE PAULRAJ: Thank you.
`MR. QUILLIN: And with us in the audience we
`have Gretchen Fritz, who is the vice president and general
`counsel for Luitpold. And we have Mr. Nobu Kadama, who is
`the director of intellectual property for Daiichi Sankyo, the
`parent of Luitpold.
`Also we have Mr. Ron Krasnow, who is here
`observing.
`MS. KOLE: If I may, Your Honor, introduce the
`people that accompany us.
`JUDGE PAULRAJ: Sure.
`MS. KOLE: This is co- counsel, Jennifer Tempesta.
`We're joined by our associate, Carolyn Pirraglia. And for
`Pharmacosmos, we have Dr. Lars Christensen, president and
`CEO, and Tobias Christensen, vice president of corporate
`strategy and development.
`JUDGE PAULRAJ: Thank you, Ms. Kole.
`We have allocated an hour and 15 minutes for each
`side for the oral argument. And I will leave it to the parties to
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`decide how they want to split up their time among the various
`portions of the hearing.
`So Petitioner, you know, when you come up, you
`can explain how much time you want for that portion of the
`hearing, and I will reserve that time.
`MS. KOLE: Very good.
`JUDGE PAULRAJ: With that, unless there is any
`other further preliminary matters, we will start with Petitioner.
`MR. QUILLIN: Your Honor, if I could, there is a
`housekeeping matter. The Board had ordered that a couple of
`papers be expunged, paper 16 in each of the --
`JUDGE PAULRAJ: Yes.
`MR. QUILLIN: But as of this morning, they were
`still there.
`JUDGE PAULRAJ: Yes. We are in receipt of that
`e-mail and have submitted a request for expungement of paper
`16 in each of those proceedings.
`MS. KOLE: And Petitioner agrees that they should
`be exchanged, so there is no disagreement there.
`JUDGE PAULRAJ: All right. Thank you.
`How much time would you like for this portion of
`the argument?
`MS. KOLE: We are planning on 50 minutes, Your
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`Honor.
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`JUDGE PAULRAJ: All right. And if you need to
`go a little past that time, I will let you go past it, just take
`time off your other portion.
`MS. KOLE: Thank you very much. That's very
`helpful. We have a lot of material to cover, and so if we need
`to allocate differently, we appreciate that flexibility.
`JUDGE PAULRAJ: That sounds good. And you
`may start.
`MS. KOLE: Okay. Thank you.
`So I will be speaking -- I'm sorry, I will be
`speaking today on behalf of Petitioner in IPR2015- 1490 and
`2015- 1493. This is the roadmap of part 1 of our remarks. We
`will be starting with a brief introduction and talk about the
`subject matter and claims of the patents at issue.
`We will then give a very high- level review of our
`argument. Then go into claim construction and talking about
`substantially non- immunogenic carbohydrate component and
`polyisomaltose, particularly as that term relates to dextran,
`and Petitioner's position that it does not include chemically
`reduced hydrogenated molecules.
`Slide 3, please.
`We will then discuss each of these references as
`they are applied to one or both patents. As you can see, there
`are four iron carbohydrate complexes involved, so there is a
`lot of material that we need to cover today.
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`And slide 4, please.
`Now, back in 2005, 2006, there was parenteral iron
`therapy for anemia, and it was effective, but the available iron
`delivery agents had undesirable health risks and dosage
`limitations.
`For example, the current iron dextran products in
`2005, 2006 were known to have a certain risk of
`anaphylactoid- type reactions, but other agents, like iron
`gluconate and iron sucrose, also had side effects that limited
`the dose and speed of administration.
`Toxic effects that could be, for example, related to
`free iron release, which we will also talk about today as labile
`iron.
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`Skip to slide 6, please.
`Now, the working examples of the '702 and '549
`patents relate to VIT-45, which is an example of an iron
`carboxymaltose complex. It was administered in the working
`examples in doses up to 1,000 milligrams, and at speeds of 15
`minutes or less without reportedly adverse effects.
`VIT- 45 is now a commercial product of Patent
`Owner known as Injectafer.
`Slide 7, please.
`This is claim 1 of the '702 patent, upon which all
`the challenged claims depend. You see that it recites a dose of
`at least about .6 grams of elemental iron. And when we talk
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`about dose today, it is always going to be about the elemental
`iron, not the dose of the iron complex being administered.
`Now, you will note that instead of being limited to
`VIT- 45 or two even iron carboxymaltose, these claims are
`directed to, in addition, iron mannitol, iron polymaltose, iron
`gluconate, and iron sorbitol complexes. They include
`functional limitations that the complex has a substantially
`non- immunogenic carbohydrate component, and it is also
`required that the complex has substantially no cross-reactivity
`with anti- dextran antibodies.
`The claims --
`JUDGE GREEN: Do you mind if I ask a question?
`Is it your understanding if you have an iron carboxymaltose
`complex or an iron mannitol complex, that those complexes
`inherently meet that functional limitation, i.e., that the
`carbohydrate complex has no -- substantially no --
`substantially not immunogenic carbohydrate component and
`substantially no cross- reactivity with anti-dextran antibodies?
`MS. KOLE: Well, I think that goes to the
`interpretation of what the substantially non- immunogenic
`means. I think that in terms of the way the specification is
`written, I think that the specification does not really give a lot
`of detail as to what substantially non- immunogenic
`carbohydrate component is, but it really is saying iron dextran
`products in the past have had risks associated with
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`anaphylaxis. Let's choose a carbohydrate to use in the
`complex that probably would not carry that risk.
`So, yes, I think the answer to your question is for
`things like iron carboxymaltose, for example, we have
`testimony from our expert that says that that probably would
`not react with an anti-dextran antibody, as one would
`understand an anti-dextran antibody to be.
`JUDGE GREEN: Do you know where that is in the
`record? Just so I can make a note of it.
`MS. KOLE: Let's see. So the -- so I believe that
`what we have in -- I am going to have to find it in the record.
`JUDGE GREEN: You can go on and have one of
`your associates find it.
`MS. KOLE: Okay. In our petition we said that the
`iron carboxymaltose complex was substantially
`non- immunogenic. And that it would not react with
`anti-dextran antibodies.
`JUDGE GREEN: So that is an inherent property of
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`the --
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`MS. KOLE: So it would be. So, yes, in that
`regard it would be. And that is in our petition. And we will
`get the cite for that, Your Honor.
`JUDGE GREEN: Thank you.
`JUDGE PAULRAJ: Each of those species of
`carbohydrate complexes listed in the Markush group -- and I
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`am talking about both the claims in the '702 patent, as well as
`the '549 patent -- this somewhat piggybacks on Judge Green's
`question.
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`Are they -- would you consider them to be a genus
`or specific compounds? In other words, you know, when you
`refer to, say, for example, iron polymaltose, you know, is
`there a sub- species or are there certain types of iron
`polymaltose that might fall into that category?
`MS. KOLE: For anything other than iron
`carboxymaltose, iron carboxymaltose has a species recited in
`the specification, but we believe that because that is not
`recited in the claim, we think that iron carboxymaltose in the
`claim means the genus.
`And for all the others, there is really no additional
`information as to species that might have particularly
`desirable properties. So we believe that they are all genus.
`JUDGE PAULRAJ: They are all genus?
`MS. KOLE: All these are terms that refer to the
`genus of carbohydrate complexes.
`JUDGE PAULRAJ: And then to your
`understanding, the additional qualification that the iron
`carbohydrate complex has a substantially non- immunogenic
`carbohydrate component, that would be an inherent property
`for any compound that falls within the genus recited in the
`Markush group?
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`MS. KOLE: Yes, yes.
`JUDGE PAULRAJ: And that's -- you have expert
`testimony supporting that?
`MS. KOLE: We have expert testimony as to iron
`polymaltose and iron carboxymaltose specifically, with regard
`to reactivity with anti-dextran antibodies.
`Iron PSCE, the polyglucose sorbitol carboxymethyl
`ether, that is the compound that is in an improper dependent
`claim. And Petitioner and Patent Owner agree that it doesn't
`fall within the scope of claim 1.
`However, for that as well, we have expert
`testimony that says that that also does not react with --
`substantially react with anti- dextran antibodies.
`JUDGE PAULRAJ: Okay.
`MS. KOLE: And we have a -- there is actually a
`figure from our reference Groman to that point as well. May I
`proceed? Oh, thank you, Jen.
`JUDGE PAULRAJ: Yes.
`MS. KOLE: So this is, this is from the '702, the
`01490 proceeding. This is Pharmacosmos Exhibit 1005. This
`is page 7, paragraph 8, last line, because I would consider --
`Dr. Linhardt's testimony: Because I would consider
`anti-dextran antibodies to be antibodies that specifically
`recognize dextran of primarily alpha 1-6 linked oligomer or
`polymer of glucose. I would not expect an anti- dextran
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`antibody to cross- react with iron carboxymaltose, in which the
`carbohydrate is primarily alpha 1-4 linked oligomer or
`polymer of glucose.
`Actually, as I am looking at that, there is also with
`regard to Van Zyl-Smit, there is also on slide 49, please. This
`is testimony from Dr. Linhardt with regard to polymaltose:
`"Because Van Zyl-Smit did not observe anaphylactoid reaction
`upon administration of iron polymaltose, and refers to iron
`polymaltose as a safe and effective way of treating iron
`deficiency, I would consider Van Zyl-Smit to teach that the
`polymaltose in the complexes is substantially
`non- immunogenic. I would not expect an anti- dextran
`antibody to cross- react with iron polymaltose, in which the
`carbohydrate is primarily an Alpha 1- 4 linked oligomer or
`polymer of glucose."
`So that for the record is the Linhardt declaration,
`01490, Exhibit 1005, page 15, paragraph 23.
`JUDGE PAULRAJ: Van Zyl-Smit deals with a
`particular formulation of iron polymaltose; is that right?
`MS. KOLE: Yes, it does.
`JUDGE PAULRAJ: And the conclusions that you
`have pointed to in slide 49, is that applicable to any
`formulation? And the reason I am asking this is Patent
`Owner's argument with respect, I believe, Exhibit 2003 -- the
`other formulation of polymaltose that they identify as, as
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`possibly causing anaphylactic reactions. Can you address
`that?
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`MS. KOLE: Yes. I think that Van Zyl-Smit
`teaches a species of iron polymaltose and recorded good
`results, that it is not anaphylactic.
`They refer to -- they refer to, in general, that they
`are not using dextran and that anti-dextran antibodies are
`known to have adverse effects for, you know, creating
`anaphylactic shock.
`So there is an implication in Van Zyl-Smit, and
`specifically where that would be would be in -- this is a
`paragraph that Dr. Linhardt had cited. This is slide 48,
`conveniently.
`"Anti- dextran antibodies are largely responsible
`for the high prevalence of side effects, including anaphylaxis
`to dextran- containing compounds." And then they go on to
`say -- and this is actually what I was going to be saying in the
`background, that there were two important considerations to
`the success of a parenteral iron compound. One is whether it
`can create an allergic effect, immune effect. And the other is
`what is the rate of free iron release.
`And this paragraph addresses both of them. So it
`goes on to say with compounds such as iron sucrose and iron
`gluconate, side effects seem to be mostly related to the rate of
`iron release.
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`Skipping ahead, the iron polymaltose dextran
`preparation, which they used here in this study releases iron
`more slowly and allows the use of TDI, which means total
`dose infusion. So you can give a lot at one time, similar to
`what the claims are covering here.
`In this respect it is similar to dextran, because
`dextran had good free iron effects. No obvious side effects
`were noted with doses containing 1 to 4 milligrams of iron
`during our study.
`So the answer to your question is that, yes, Van
`Zyl-Smit talks about a species. I think that it is reasonable
`that it could be generalized based on this paragraph, which has
`been cited in the record as indicated on this slide.
`However, we're also taking the position that the
`disclosure of a species would anticipate a genus. So shall I go
`on?
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`JUDGE PAULRAJ: Yes, please.
`MS. KOLE: Okay. Back to slide 8, please. We
`have actually covered now a lot of the ground of the first part
`of the talk.
`And slide 8 shows claim 1 of the '549 patent, upon
`which all the claims of that patent depend.
`And you will see that, similarly, it requires a
`threshold of at least about .6 grams of elemental iron. And it
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`now recites a group of iron carbohydrate complexes that omits
`iron carboxymaltose, but includes iron polyisomaltose.
`It now functionally does not have the limitation
`that the complex needs to be substantially not cross-reactive
`with anti- dextran antibodies, although that is found in one of
`the dependent claims.
`One can look at this main claim for the '549 and
`the '702 patent, and it would seem apparent that the discovery
`that is being highlighted by the claims is not a better
`parenteral iron supplement, but, rather, it is being able to give
`a high dose.
`And this is actually consistent with a number of
`statements that Patent Owner has made on the record.
`Slide 9, please.
`This is a citation that is of record and Patent
`Owner has relied upon it. I am going to read it. "Various
`pharmacokinetic studies suggest the doses of iron complexes
`higher than 200 milligrams of iron are generally unsuitable
`and that the conventional therapy model prescribes repeated
`applications of lower doses over several days."
`Petitioner disagrees with this position, Your
`Honors. And Geisser 1992 is, while instructive, it is not
`supportive of this point. And we think it is useful to just talk
`about that reference, even though it is from 1992.
`Slide 10, please.
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`So Geisser 1992 actually disclose that as regards
`iron dextran and iron dextran complexes, that they had a great
`deal of complex stability, so the free iron kind of concern that
`we just were talking about. And this leads to the observed low
`toxicity and lends for their use as particularly intramuscular
`injection agents, but also as vehicles for total dose infusion.
`Slide 12 -- slide 11, please.
`Geisser also teaches that because of this complex
`stability, iron dextran was safe and effective at high
`therapeutic doses. So another point that we want to make,
`Your Honors, is that the high doses are really attributable to
`complex stability and low free iron.
`The avoidance of anaphylaxis, which obviously is
`very important. Anaphylaxis, as you know from people that
`have peanut allergies -- we do not mention peanut allergies on
`the record -- but you just can have a small dose and that can
`have serious consequences.
`So consistently here, Geisser is saying: Well, from
`an iron standpoint, you actually can give iron dextran in high
`doses.
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`And 200 milligrams comes in as the dose given to
`the mouse. The mouse was given 200 milligrams per kilogram,
`which actually didn't end up being 200 for the mouse, but it
`was not taught as a threshold that couldn't be crossed. And
`that's the point that we wanted to make.
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`Also, if you could go back to slide 10, please.
`We also wanted to highlight the terminology. You
`see here that Geisser refers to dextran, parens, polyisomaltose.
`And as you are aware, this is also another issue that has been
`disputed in the parties. And we just want to remark that in
`Geisser 1992, this formulation was cited.
`Slide 12, please.
`So Geisser 1992 was in the last Millenia. And now
`we're talking about something more contemporary, the earliest
`priority date for the '702 and '549 patents being January 6,
`2006. By that time, as regards iron complexes in general,
`more than 200 milligrams and sometimes much more than 200
`milligrams of iron carbohydrate complex were used.
`These are some examples. Auerbach in 2004
`reports iron doses of 1,000 to 3,000 milligrams given as the
`low molecular weight iron dextran known as InFed. Cosmofer,
`which is the European equivalent of InFed had already been
`approved in 2005 for doses of 20 milligrams per kilogram
`given as a total dose infusion for an 80 kilogram subject,
`176- pound person. That would be 1600 milligrams of
`elemental iron.
`And moving away from the iron dextran category,
`Spinowitz in 2005 administered iron PSCE, one of the
`compounds covered by the claims in both patents, to deliver
`510 milligrams of iron in 17 seconds. So, again, 200
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`milligrams was not regarded as threshold that was too
`dangerous to cross.
`JUDGE PAULRAJ: Did these references discuss
`any concerns about anaphylactoid reactions?
`MS. KOLE: Yes, I mean, particularly Spinowitz.
`And this is in the -- our petitions, when we talk about the
`background of the art. It was recognized that iron dextran did
`have, all of the -- all of the iron carbohydrate complexes have
`some anaphylactic risk, but Spinowitz particularly says that
`there was an anaphylactic risk associated with the iron dextran
`products that were available and that it would be good to find
`an agent that, you know, that improved upon that risk.
`And as we will see, Spinowitz's product is, in fact,
`a modified form of dextran.
`We also aren't saying, Your Honors, that 200
`milligrams or lower doses in general were not more commonly
`used. We believe that they probably were commonly used and
`maybe even preferably used.
`But that is not the same thing as a teaching against
`doses that were higher. And we see that there are a number of
`instances where higher doses were used.
`And moving on to the references we will be talking
`about today, slide 13. Groman, Van Zyl-Smit, and Geisser all
`teach higher doses of iron carbohydrate species that are
`covered by the claims.
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`And Groman teaches doses of up to 600 milligrams
`of elemental iron, given as iron polyisomaltose or iron PSCE.
`We will call Spinowitz 510, now this is 600, up to 600.
`Iron polymaltose was taught by Van Zyl-Smit as a
`vehicle for administering doses of 900 to 3200 milligrams of
`elemental iron. And Geisser taught doses of 500 to 1,000
`milligrams of elemental iron by iron carboxymaltose.
`Each of these references teaches that the respective
`iron carbohydrate complexes have the advantage of low
`immunogenicity and low iron toxicity.
`JUDGE PAULRAJ: In your view Groman’s
`teaching of a dosage up to 600 milligrams, that reads on the
`claim limitation of a single dosage of at least above 0.6
`grams?
`
`MS. KOLE: Yes, we do. Yes, we do. We
`understand that the Patent Owner has cited the Atofina case.
`JUDGE PAULRAJ: Yes.
`MS. KOLE: And we believe that there is nothing
`in the record to show that 600 milligrams has any kind of
`criticality that's associated with it. There is no reason to
`believe that the invention would operate differently at doses
`up to 600, and then you get a particular effect.
`JUDGE PAULRAJ: Well, I am more interested in
`this quote from Atofina, and I have it right in front of me.
`MS. KOLE: Okay.
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`JUDGE PAULRAJ: It says, "The disclosure of a
`range is no more a disclosure of the end points of the range
`than it is of each of the intermediate points."
`And I am not sure if you are familiar with that
`statement in Atofina.
`MS. KOLE: I am, Your Honor.
`JUDGE PAULRAJ: Explain to me why -- although
`we have a range here in the prior art, up to 600 milligrams,
`you know, if that statement in Atofina is meant to mean
`anything, that 600 milligrams is just an end point of the range,
`but it doesn't necessarily mean that that is a particular dose
`essentially used. Any I misreading Atofina?
`MS. KOLE: I don't think so, but I think here that
`Atofina was about that you had -- it was almost like a
`species/genus argument, where it was discovered that,
`although a broader range was known, that there was a narrower
`range where things changed once you fell within that range.
`And in this particular case, there is no reason to
`think that that happened. This is not an argument that is in
`our record. So please tell me if this is inappropriate, but it
`seems like you have 600 milligrams and 500 milligrams, 510
`milligrams was the next dose down in the art.
`So I don't know that there is a reason that 600
`milligrams provided anything different. As you have all these
`different iron carbohydrate species that are recited in the
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`claims, that the same observation would apply to all of them,
`seems unlikely. So I don't think that there is, that there is a
`criticality.
`There is also the phrase of "about," so I think that
`"about" also makes a difference, that it is not dealing with the
`end point in any kind of a concrete way.
`JUDGE PAULRAJ: So the "about" can, in the
`claim language, can bring it to within the range taught by
`Groman?
`
`MS. KOLE: Yes. Yes, Your Honor.
`Slide 14, please.
`I think we're touching on the same issues here, the
`substantially non- immunogenic carbohydrate component, and
`polyisomaltose.
`Slide 15, please.
`So with regard to substantially non- immunogenic
`carbohydrate component, Petitioner's proposed construction is
`a carbohydrate component, not the complex as a whole,
`resulting in a low risk of anaphylactoid hypersensitivity
`reaction. And Patent Owner's proposed construction, "a
`carbohydrate component as part of the iron complex, having an
`incidence rate of anaphylactoid/hypersensitivity reactions
`lower than that for dextran, when administered to a cohort
`large enough to reveal adverse event, where the adverse event
`rate for dextran is 0.6 percent.
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`Slide 16, please.
`JUDGE PAULRAJ: Let me focus on that claim
`construction dispute a little bit. So going back to it, if you
`have it open there, even with the construction that Petitioner
`proposes, which is the construction the Board had in the
`Institution decision, is it Petitioner's understanding that the
`low risk would be implicitly less than prior art dextran? Is
`that -- I saw that in your reply papers, right?
`MS. KOLE: Yes.
`JUDGE PAULRAJ: So you still have to compare it
`to dextran to determine whether or not that is a risk?
`MS. KOLE: I think that there isn't a lot said in the
`specification about what low risk is, but I think it is fair to say
`that because the focus of much of the, at least the prosecution
`history, was on immunogenicity. And we're talking about
`whether the carbohydrate component is substantially
`non- immunogenic.
`I think that it is reasonable to say, especially in
`view of the broadest reasonable interpretation of the claims,
`that what we're talking about is a lower rate than dextran, but I
`think not just -- this is one of the disputes between the parties,
`Your Honors, in terms of what that word means.
`And I think that it would be lower than previously
`available iron dextran products, and that's the phrasing that we
`use in our papers, and in our reply.
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`So, for example, InFed that I had mentioned
`earlier, the European equivalent, Cosmofer, what we will refer
`to as the old dextran, we think it is reasonable to say that the
`low risk would be lower than the old dextran products.
`JUDGE PAULRAJ: Okay. Well, with that
`understanding, do we have anything in the record as to what
`the risk might be with InFed or any other prior art dextran
`products?
`
`In other words, are we -- I understand you dispute
`Patent Owner's additional limitation of the adverse event rate
`for dextran is 0.6, but how do we compare to dextran, you
`know, if we don't know what the risk associated with dextran
`is?
`
`MS. KOLE: I --
`JUDGE PAULRAJ: Is there a number that we can
`associate as, as a risk associated with dextran?
`MS. KOLE: I think that then we get caught in
`what does the specification and prosecution history disclose --
`and I don't think that fairly it does disclose -- I think
`that .6, .6, as Patent Owner has talked about it, is the risk
`associated with the complex. It is not associated with the
`carbohydrate component.
`JUDGE PAULRAJ: Right.
`MS. KOLE: That contradicts -- I think actually go
`to the next slide -- it contradicts the threshold of less than
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`about 5 percent that's in the specification. But that's for the
`complex as a whole.
`I think that with regard to the low risk for the
`carbohydrate component, we go to -- and I am going to read a
`statement from our reply -- for the record at page 10, citing
`Exhibit 1001, this is in the 1493 proceeding.
`The specification guides a POSITA to identify a
`carbohydrate component that is essentially -- that is
`substantially non- immunogenic and use it in the complex with
`iron.
`
`And that's what we see the various references
`doing, Your Honor. They will say dextran had these problems
`associated with it. We're going to build an iron carbohydrate
`complex with something which is not the old dextran.
`And so the approach that Groman took was one
`thing they do was they reduced and they made much smaller
`the dextran. One thing that Van Zyl-Smit did was use
`polymaltose. One thing that Geisser did was use iron
`carboxymaltose.
`And they all say -- so Groman, you know, says
`that, you know, that this provides a better product
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