trials@uspto.gov
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`571-272-7822
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`IPR2015-01835, Paper No. 54
`IPR2015-01836, Paper No. 56
`January 18, 2017
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`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
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`COALITION FOR AFFORDABLE DRUGS VIII, LLC,
`Petitioner,
`
`v.
`
`THE TRUSTEES OF THE UNIVERSITY OF
`PENNSYLVANIA,
`Patent Owner.
`____________
`
`Case IPR2015-01835 (Patent 8,618,135 B2)
`Case IPR2015-01836 (Patent 7,932,268 B2)
`____________
`
`Held: December 1, 2016
`____________
`
`
`
`
`BEFORE: MICHAEL P. TIERNEY, LORA M. GREEN,
`GRACE KARAFFA OBERMANN, Administrative Patent
`Judges.
`
`
`The above-entitled matter came on for hearing on Thursday,
`
`December 1, 2016, commencing at 1:59 p.m., at the U.S. Patent
`and Trademark Office, 600 Dulany Street, Alexandria, Virginia.
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`571-272-7822
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`IPR2015-01835, Paper No. 54
`IPR2015-01836, Paper No. 56
`January 18, 2017
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`COALITION FOR AFFORDABLE DRUGS VIII, LLC,
`Petitioner,
`
`v.
`
`THE TRUSTEES OF THE UNIVERSITY OF
`PENNSYLVANIA,
`Patent Owner.
`____________
`
`Case IPR2015-01835 (Patent 8,618,135 B2)
`Case IPR2015-01836 (Patent 7,932,268 B2)
`____________
`
`Held: December 1, 2016
`____________
`
`
`
`
`BEFORE: MICHAEL P. TIERNEY, LORA M. GREEN,
`GRACE KARAFFA OBERMANN, Administrative Patent
`Judges.
`
`
`The above-entitled matter came on for hearing on Thursday,
`
`December 1, 2016, commencing at 1:59 p.m., at the U.S. Patent
`and Trademark Office, 600 Dulany Street, Alexandria, Virginia.
`
`
`
`
`
`
`
`
`--and—
`
`KEVIN S. PRUSSIA, ESQUIRE
`Wilmer Cutler Pickering Hale and Dorr LLP
`60 State Street
`Boston, Massachusetts 02109
`
`WILLIAM G. JAMES, ESQUIRE
`Goodwin Procter LLP
`901 New York Avenue NW
`Washington, DC 20001
`
`Case IPR2015-01835 (Patent 8,618,135 B2)
`Case IPR2015-01836 (Patent 7,932,268 B2)
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`APPEARANCES:
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`ON BEHALF OF PATENT OWNER:
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`Case IPR2015-01835 (Patent 8,618,135 B2)
`Case IPR2015-01836 (Patent 7,932,268 B2)
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`P R O C E E D I N G S
`- - - - -
`JUDGE GREEN: Thank for your patience. Good
`morning. Welcome, everyone. This is the final oral hearing in
`IPR2015-01835 and IPR2015-01836. These proceedings involve
`Patent Numbers 8,618,135 and 7,932,268.
`At this time we would like counsel to introduce
`yourselves and your colleagues beginning with Petitioner.
`DR. GONSALVES: My name is Dr. Gregory
`Gonsalves representing Petitioner. With me is my colleague,
`Chris Casieri.
`MR. JAMES: My name is William James from
`Goodwin Procter LLP. With me today is Cynthia Hardman and
`Nick Mitrokostas, also from Goodwin Procter, and also today
`from the University of Pennsylvania is Kathryn Donahue,
`Director of Legal Affairs and Associate General Counsel from the
`University of Pennsylvania.
`JUDGE GREEN: Thank you. Welcome to the Board.
`MR. PRUSSIA: And I'm Kevin Prussia from Wilmer
`Hale, also on behalf of the Patent Owner.
`JUDGE GREEN: Okay. Thank you. Anybody else?
`(No response.)
`JUDGE GREEN: Okay. Thank you.
`Consistent with our previous order, each party has 60
`minutes to present its arguments. Petitioner will present first its
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`case-in-chief as to the challenged claims and may reserve rebuttal
`time to respond to the arguments made by the Patent Owner.
`Thereafter, Patent Owner will respond to the Petitioner's case and
`may also address its Motion to Amend. Patent Owner may
`reserve rebuttal time to address Petitioner's arguments as to the
`Motion to Amend.
`Counsel for Petitioner, you may proceed. Would you
`like to reserve rebuttal time?
`DR. GONSALVES: May I believe reserve 15 minutes
`of rebuttal time?
`JUDGE GREEN: Whenever you're ready.
`MR. GONSALVES: We're going to go into all the
`nitty-gritty details in just a moment, but one of the overarching
`themes of all the arguments is that Patent Owner's arguments are
`not commensurate with the scope of the claims and you'll see that
`theme over and over and over again through my presentation.
`Throughout the day today, I'll just be presenting
`documents from the record in this case.
`JUDGE GREEN: And if you could refer to where
`you're finding this in the record as to each exhibit, that would
`help us some when we look at the transcript.
`DR. GONSALVES: Sure. So this is the Patent Owner's
`Response, page 7.
`And one of the things that the Patent Owner argued was
`that the claim should be construed according to the same standard
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`that's applicable in District Court and it states, while the Board
`has adopted the broadest reasonable interpretation, a claim
`construction standard by regulation, the Patent Owner
`respectfully submits that this standard is legally impermissible for
`the reasons now being considered by the Supreme Court.
`Since the Patent Owner wrote this, the Supreme Court,
`as everybody knows, has unanimously held that it is legally
`permissible for the Board to use the BRI standard in IPRs and
`that was the Cuozzo Speed. It was actually the very first IPR that
`was on appeal.
`According to the Supreme Court in that case, the BRI
`regulation represents a reasonable exercise of the rulemaking
`authority that Congress delegated to the Patent Office, which
`encourages the Applicant to draft the claims narrowly. This has
`been used by the Patent Office for more than a hundred years and
`it is not unfair to the Patent Holder in any obvious way.
`JUDGE GREEN: So are you making these arguments
`in response to Patent Owner's request that we interpret the claims
`to basically mean the forced titration.
`DR. GONSALVES: Sure. This is my next -- what I'm
`presenting right now.
`Now, one of the things in light of this more narrow
`claim construction standard that the Patent Owner has indicated
`that the Board should follow, which the Supreme Court has now
`said the Board should not follow, it says here -- this is page 36 of
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`the Patent Owner Response and it indicates that in the -- this is
`the Patent Owner's argument. In the claimed regimen, therefore,
`patients continue receiving higher doses of lomitapide
`notwithstanding the presence of side effects at the lower dose.
`The claimed dosing regimen is, therefore, fundamentally different
`from the Pink Sheet, dose-finding study, which proposes testing a
`number of doses in order to identify a single dose that is both
`efficacious and safe.
`So here the Patent Owner is arguing that their claims
`cover one particular -- a purpose for having the escalating dosage
`and not another purpose such as to identify a single dose.
`Now, it's not just the Patent Owner. This is from
`Exhibit 1058. It's the deposition of Dr. Sacks, the transcript of
`that deposition. So it's not just the Patent Owner's basis for their
`argument, but also the experts base their opinions on the
`argument for a very narrow claim construction and you can see
`here that they're reading at this point in the transcript from Dr.
`Sacks' declaration.
`It says as follows, and then you said in your declaration
`it means that the claimed method of treating a human patient
`requires a forced-dose titration regimen, including but not limited
`to at least three stepwise increasing dose levels of lomitapide. Do
`you see that? The answer is yes. So it's also their experts that are
`relying on this particular claim's very narrow claim construction.
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`So that was one of their experts. This next excerpt is
`from the deposition transcript of Dr. Kimball and it is at Exhibit
`1056. This is page 181 and it's talking about what's in paragraph
`125 of Dr. Kimball's declaration.
`And it says in that paragraph, in contrast, the purpose of
`dosing regimens claimed in the patents at issue is to stop with
`subtherapeutic doses and slowly titrate upward to allow the body
`to adapt to the presence of the MTP inhibitor and actually reduce
`the incidence of side effects as the dose increases. Do you see
`that? The answer is, yes, that's correct.
`So this is both of their -- two of their experts and
`actually it's consistent with the testimony of all of their experts
`that the basis for their opinion is founded on this very narrow
`construction interpretation of the claims.
`So now we're turning to Exhibit 1056. This is, again,
`from the transcript of the deposition of Dr. Kimball. At the very
`end, the question asks, is there any mention of side effects in the
`claims of the patent? And Dr. Kimball responds, no, because
`there is nothing in the claim that says you give a dosage to a
`patient and you see that the patient has side effects and then you
`give them another dosage.
`The claim just requires three steps of dosages
`independent of whether or not a person is experiencing side
`effects. The method of the claim doesn't depend at all on whether
`or not a patient is experiencing side effects.
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`Case IPR2015-01836 (Patent 7,932,268 B2)
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`Similarly, this is back to the deposition transcript of Dr.
`Sacks. I believe it's Exhibit 1058. The question was asked, do
`you know, does that term forced-dose titration regimen appear in
`the claims at all? He says, I don't recall seeing that in the claims.
`Now, this is Exhibit 1001, which is the '135 patent. It's
`the patent at issue in this IPR proceeding and so you don't have to
`take my word for it. I guess this copy is a little bit difficult to
`read because the patents are printed in small type.
`But looking at the patent itself, you can see that there
`are no steps, as I said before, that say that the dosage is dependent
`on whether or not a patient experiences side effects while being
`treated with the medicine. It's possible, for example, and the
`claims encompass the case where you have a patient, they come
`in and they're administered three dosage levels and they don't
`experience any side effects at all.
`The claim encompasses that particular case. It's not
`limited to a particular purpose of giving a patient medicine, even
`after that patient has experienced side effects.
`So the construction that was proposed by the Patent
`Owner, which is evident throughout all of their arguments, not
`only in distinguishing the prior art, but also on the secondary
`considerations of nonobviousness, we believe that the claim
`construction which is clearly indicated throughout their papers is
`wrong for three separate reasons.
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`As we just saw from the claims and as indicated by the
`testimony of Patent Owner's experts, there is no suggestion in the
`claims that they are restricted to a forced-dose method
`notwithstanding the presence of side effects at lower doses for the
`purposes of improving tolerability.
`Now, secondly, is we cited a case in our Petitioner's
`Reply, a Federal Circuit case, SuperGuide Corp. v. DirecTV
`Enterprises, but as you know there are a lot of Federal Circuit
`cases that say pretty much the same thing that it is impermissible
`to import limitations from the specification into the claims.
`Now, the third thing is, if you look at the Patent
`Owner's Response at page 8, which is the claim construction
`section, there is no -- the Patent Owner did not provide any
`reasons whatsoever as to why their proposed narrow construction
`is proper.
`So for these reasons that I just mentioned, the claims
`should be construed under the broadest reasonable interpretation
`standard and it should be construed to encompass any method
`that treats a subject within this claimed stepwise increasing dose
`ranges of lomitapide.
`So now we move on to beyond claim construction and
`we're looking at Ground 1, which is that the Claims 1 to 10 are
`obvious in view of the Pink Sheet 2004 and Chang, and I will put
`up Patent Owner's argument where they attempted to distinguish
`the claims from the prior art.
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`And they state as follows, in the claimed regimen,
`therefore, patients continue receiving higher doses of lomitapide
`notwithstanding the presence of side effects at the lower dose.
`The claimed dosing regimen is, therefore, fundamentally different
`from Pink Sheet 2004's dose-finding study which proposes testing
`a number of doses in order to identify a single dose that is both
`efficacious and safe.
`So, once again, they're attempting to distinguish the
`prior art from something that's not a requirement of the claim.
`The argument that I just read from the Patent Owner's response is
`not commensurate with the scope of the claim because nothing in
`the claim requires performing the method for one particular
`purpose, in particular improved tolerability.
`So even if the protocols in the Pink Sheet and the statin
`dose titration were interpreted to be dose-finding studies as
`alleged by the Patent Owner, they would nonetheless not differ
`from the claimed invention.
`Nothing in the claims requires forcing higher doses of
`lomitapide into a patient after the patient experiences side effects.
`The claimed treatment method is not restricted to patients who
`experience side effect after the first or second dose. It also
`applies to subjects that do not experience side effects.
`The Patent Owner failed to even attempt to explain how
`the protocol of the Pink Sheet as applied to the latter group of
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`subjects, those people that don't receive any side effects, would
`differ from the claimed method.
`Now, the Patent Owner also relied on clinical trials for
`it's alleged reduction to practice and even the clinical trials that it
`relied upon --
`JUDGE GREEN: Excuse me, the reduction to practice
`is in the Motion to Amend, correct?
`DR. GONSALVES: I think it also may have been in
`their Preliminary Response, but I don't know with absolute
`certainly.
`JUDGE GREEN: We're going to stick to -- I think that
`that is something that's better because they rely on it very heavily
`in their Motion to Amend and I think that's more rebuttal than it is
`your case-in-chief.
`But they did have other arguments besides the
`forced-dose titration. They do argue the Pink Sheet doesn't
`record any results, that there are no reported results from Chang,
`there's no peer review or anything else like that.
`DR. GONSALVES: There's a lot of issues --
`JUDGE GREEN: And no reasonable expectation of
`success based on that. How do you respond to that?
`DR. GONSALVES: Well, there were a lot of issues
`that you just -- and --
`JUDGE GREEN: I understand.
`DR. GONSALVES: -- I'm getting there if that's okay.
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`Another argument that they made, and this is page 37 of
`the Patent Owner Response, is that the Pink Sheet, in order to
`distinguish the Pink Sheet, to attempt to, it relates to testing
`dosage, doses that are lower than doses that exhibited toxicity,
`which is entirely different according to the Patent Owner from the
`'135 claims, which relate to administration of doses that are
`higher than the 25 milligrams per day doses that led to
`discontinuation of lomitapide development.
`The important point here is that this argument is also
`not commensurate with the scope of the claim because Claim 1
`doesn't require 25 milligrams per day. It requires the lower
`bound on the highest dosage is about 10 milligrams per day and
`that's less, much less than the amount of lomitapide that was
`found to have caused side effects.
`So, again, even under the Patent Owner's interpretation
`of the Pink Sheet, it would still -- the Pink Sheet would still not
`differ based on that argument from the claimed invention because
`dose ranges less than 25 milligrams a day, in fact, because the
`claim says about 10 milligrams a day, it can be less than 10
`milligrams a day. So claimed dosage ranges less than that are, in
`fact, encompassed by the claim.
`There's also another point where they made an argument
`and then I'm going to get on to the motivation to combine. That's
`also not commensurate with the scope of the claim and they had
`argued or tried to distinguish the Pink Sheet by stating that it
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`discloses a very slow increase in dosing amounts, but this
`argument is also not commensurate in the scope of the claim
`because the claims encompass a dose increment as little as 3
`milligrams, for instance, from 2 milligrams of a first dose to 5
`milligrams of a second dose and this is recited in Claims 1, 9 and
`10.
`
`So even the characterization of having 5 milligrams a
`day, which was in reference to Stein, would still be encompassed
`by the claim because the claim requires as little as a difference of
`3 milligrams from one dose to the next.
`JUDGE TIERNEY: I have a question about convention
`and skill. The claims are directed to a method of treating a
`subject. Is the subject limited to human?
`DR. GONSALVES: No. A subject is not limited to
`humans. If it intended to be limited to humans, it would have
`said humans there.
`JUDGE TIERNEY: So what is it open to?
`DR. GONSALVES: Well, it certainly opens it up to
`animals also. It opens -- when it says subject, a subject is a
`broader term than a human being.
`JUDGE TIERNEY: So would human trials be required
`for showing a reasonable expectation of success for these claims?
`DR. GONSALVES: No, I don't believe it would and
`we'll get on to this line of discussion, but that is a way to establish
`a reasonable expectation of success, but it's not the only way. It
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`can be -- and our argument is based upon test results from
`implitapide that's reported in the literature as well as animal
`testing and there are many factors that our experts relied on for
`indicating that there would be a motivation to combine and there
`would be a reasonable expectation of success of achieving the
`claimed invention.
`Now, one of the arguments that -- with respect to the
`motivation to combine that the Patent Owner had made saying
`that there was no motivation to combine, is that -- and this is a
`quote from page 30 of the Patent Owner's Response, Chang
`describes at least six other MTP inhibitors.
`This argument was actually already addressed in your
`Institution Decision. You see at the bottom of page 17 of your
`Institution Decision and it reads as follows, the fact that Chang
`discloses MTP inhibitors other than lomitapide does not by itself
`make the selection of lomitapide any less obvious, and then it
`quotes a Federal Circuit case.
`And in the Federal Circuit case, the Merck v. Biocraft
`case, the Federal Circuit held that the prior art's disclosure of a
`multitude of combinations failed to render any particular
`formulation less obvious. And another Federal Circuit case,
`Perricone versus Medicis that we cited in our papers, the Federal
`Circuit rejected the notion that 1 of 14 listed ingredients cannot
`anticipate because it appears without special emphasis and a
`longer list.
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`So, therefore, the Patent Owner's identification of
`merely six other MTP inhibitors in Chang is not nearly enough to
`show that the selection of lomitapide from the list would not have
`been obvious, and also there would have been a reason for a
`person of ordinary skill in the art to select lomitapide because
`implitapide and lomitapide are specifically described in Chang as
`having similar efficacy in humans.
`So they would have been -- a person of ordinary skill in
`the art at the time of the effective filing date of the '135 patent
`would have been directed to lomitapide as the MTP inhibitor
`based upon the sentence in Chang that indicates that they have
`similar efficacy in humans.
`Now, on page 18 of the Institution Decision, the Board
`also noted this, it's stated as follows, Chang discusses the clinical
`efficacy of CP-346086, and then notes that similar efficacy was
`reported for implitapide and lomitapide. Given that implitapide
`and lomitapide are from the same class of therapeutics that is
`MTP inhibitors and that they are known to have similar clinical
`efficacy, we determine that there was a reasonable basis for --
`that a person of ordinary skill in the art would have used
`lomitapide as taught by Chang for implitapide in the method of
`the Pink Sheet.
`Now, the other thing, and this is in response to one of
`the issues that arose when you were speaking with me earlier, the
`Patent Owner argued extensively in their briefs that a person of
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`Case IPR2015-01836 (Patent 7,932,268 B2)
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`ordinary skill in the art would have been dissuaded from
`lomitapide because -- and this is a quote from page 27 of their
`Response, development of lomitapide had been halted by BMS
`due to toxicity in phase I and II clinical trials.
`But this argument is wrong for two reasons. First, the
`proper inquiry is whether a person of ordinary skill in the art
`would have been motivated to develop lomitapide as of the
`effective filing date of the '135 patent. That's March of 2005, not
`at the time that Chang was published. That's number one.
`Also as of March 2005, a person of ordinary skill in the
`art would have understood that the toxicity in the clinical trials
`was due to high doses, not the low doses required by the claims.
`JUDGE GREEN: Now, one of the things I think Patent
`Owner was arguing is that the ordinary artisan would not have
`necessarily understood that the toxicity was due to the high doses
`alone. Can you explain this to an exhibit or some evidence that
`the ordinary artisan would have been aware of that?
`MR. GONSALVES: Well, there's an absence of
`evidence indicating that side effects occurred at the lower doses
`of lomitapide. That was available to a person of ordinary skill in
`the art as of the filing date of the '135 patent.
`JUDGE GREEN: But the fact that they were
`abandoning it, doesn't that suggest that, you know, the low doses
`weren't efficacious for what they were trying to do, so there was
`no reason for them to continue to develop the drug? I don't know
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`if an absence is that telling. Because if they thought that it was
`going to be efficacious, even at those lower doses where you
`wouldn't have seen the toxicities, they may have continued its
`development.
`So I think the absence of evidence may suggest that
`some doses were toxic and it wasn't efficacious of the doses that
`you could dose.
`DR. GONSALVES: Yeah, I understand, but there are
`other reasons. For instance, there is evidence in the record
`indicating, in fact, the Technology Donation Agreement where
`the technology was donated from BMS to the universe.
`JUDGE GREEN: But was that publicly available?
`DR. GONSALVES: No, I don't believe it was, but
`there's an indication there that it was based upon commercial
`reasons.
`JUDGE GREEN: No, I understand that, but that
`wouldn't have been part of the understanding of the ordinary
`artisan.
`
`DR. GONSALVES: Well, I think the ordinary artisan,
`however, would have understood that a person of ordinary skill in
`the art as defined by the Patent Owner would have understood
`that, you know, large pharmaceutical companies, they have a
`certain market, that they would need to have a certain size market
`that they would need to have in order to justify proceeding with
`the drug and that just because they abandoned that market for one
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`particular purpose doesn't mean it can't be used for other
`purposes, for instance, an HoFH is in the record and also as an
`add-on therapy to statins.
`So there could be a smaller market which a smaller
`company or institution may be interested in and a larger company
`that needs to have so much profit per drug, otherwise they
`discontinue it, large pharmaceutical companies, and a person of
`ordinary skill in the art then and now and anytime in between
`would understand that large pharmaceutical companies also --
`often abandon drugs for commercial business reasons.
`One of the things that the Patent Owner argued to
`indicate that a person of ordinary skill in the art would have been
`dissuaded from lomitapide, what they alleged was that the
`concern of off target toxicity, phospholipidosis and hERG would
`have dissuaded a person of ordinary skill in the art from using
`lomitapide, but there is a quote from the Patent Owner's expert,
`Dr. Kimball, and this at Exhibit 1056, the transcript of his
`deposition.
`And the question was asked, now were either of these
`compounds, lomitapide and implitapide, known in the 2004-2005
`time frame to exhibit off target toxicity. And the answer from Dr.
`Kimball is there was nothing in the public domain at that point in
`time that I'm aware of.
`Dr. Kimball also acknowledged at page 163, lines 16 to
`22, of his -- in his transcript of his deposition that an article by
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`BMS specifically addressing lomitapide and its development of
`MTP inhibitors fails to even mention either phospholipidosis or
`hERG inhibitions as a possibility.
`And I also direct the Board's attention with respect to
`motivation to combine as to something that it wrote in the
`Institution Decision on page 19, which I've highlighted here so
`you can also read.
`JUDGE GREEN: Dr. Gonsalves, I know you keep
`going back to our Institution Decision. We're aware of our
`Institution Decision and that was a decision on institution based
`on the evidence that we had at the time. I'm just saying I just
`don't know how helpful this is at this point in the proceeding.
`MR. GONSALVES: Well, it's not the only reason why.
`The reasons that you set forth in the Institution Decision are not
`the only reasons why a person of ordinary skill in the art would
`have pursued it.
`JUDGE GREEN: No, I understand, but you keep going
`back to the Institution Decision. You know, we wrote the
`Institution Decision. We're aware of it. We know what we put in
`it and they were based on the evidence at that time.
`DR. GONSALVES: Right.
`JUDGE GREEN: So we're in a different position now.
`DR. GONSALVES: You know, those reasons -- I
`understand what you're saying. The reasons that existed then still
`exist today and they're not the only reasons why a person of
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`ordinary skill in the art would have been motivated to pursue
`lomitapide --
`JUDGE GREEN: And I think we can go into --
`DR. GONSALVES: -- but they are among them.
`Now, the thing that was also mentioned by Dr. Zusman
`in his supplemental declaration is that because a person of
`ordinary skill in the art would have been motivated to pursue
`lomitapide to treat rare disorders and as an add-on therapy of
`statins, he comes to the conclusion at paragraph 124 of his
`supplemental declaration which is Exhibit 1049, is that a person
`of ordinary skill in the art would not have been dissuaded from
`pursuing treatment with lomitapide as lower dosage, such as
`those within the claimed ranges and, remember, the claimed
`ranges is even less than 10 milligrams per day and the side effects
`didn't occur until at the minimum 25 milligrams per day.
`And also there are several reasons why a person of
`ordinary skill in the art would have had a reasonable expectation
`of success in using the Pink Sheet protocol with lomitapide. The
`Pink Sheet specifically acknowledges the toxicity seen in other
`studies, noting that that was most likely due to high doses used
`and an escalating dose would be used to determine a safe and
`tolerable dose.
`Chang notes that both implitapide and lomitapide have
`been the subject of clinical studies and that's at Exhibit 1015 on
`page 566. Chang also reports the results of a study performed
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`with WHHL rabbits, which is an animal model for homozygous
`familial hypercholesterolemia in which administration of
`lomitapide and implitapide showed a reduction in total plasma
`cholesterol and triglycerides. And then Chang indicated that
`implitapide and lomitapide had similar efficacies.
`Now, there's another quote from -- and I'll give you the
`cite. It's on page 36 of Exhibit 1058, which is the deposition of
`Dr. Sacks, who is one of Patent Owner's experts, and he
`acknowledged on page 35 that it would be reasonable for a person
`of ordinary skill in the art to look to numbers of the same
`therapeutic class in developing a dosing regimen.
`Also, one point is, again, getting back to the scope of
`the claims, the claims recite very, very broad ranges, in fact, at
`the lower end it's very low doses of lomitapide. So the Patent
`Owner's arguments with respect to a reasonable expectation of
`success are not -- also not commensurate with the scope of the
`claims, because the Petitioner need not show that it would have
`been obvious for a person of ordinary skill in the art to have used
`the identical dosing regimen for lomitapide that was specified for
`implitapide on the Pink Sheet.
`Rather, the Petitioner need only show that it would have
`been obvious for a person of ordinary skill in the art to use a
`dosing regimen for lomitapide that falls within the very broad
`dosing ranges that are recited in the claims.
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`Now, with respect to the ground of rejection of Chang
`and Stein, again, the Patent Owner repeated the arguments that
`are not commensurate with the scope of the claims that was set
`forth for the Pink Sheet and Chang. They repeated those
`arguments for the different combination of Chang and Stein and
`I'm quoting from page 51 of the Patent Owner Response where
`they state, a dose-finding regimen is fundamentally different from
`what is claimed in the '135 patent, which requires that a patient be
`forced to titrate, notwithstanding the appearance of side effects or
`intolerability at the lower dose.
`But as I said before and as you've seen from the claims
`in the patent, the claims do not require a forced titration
`notwithstanding the side effects or intolerability.
`JUDGE GREEN: Now, can you address the availability
`of Stein's prior art because Patent Owner still argued that in their
`Response and they did show that the hyperlink that wa
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