Trials@uspto.gov
`571-272-7822
`
`
`
`
`Paper No. 90
`Entered: February 25, 2021
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`MYLAN PHARMACEUTICALS INC., DR. REDDY’S
`LABORATORIES, INC., DR. REDDY’S LABORATORIES, LTD., and
`SUN PHARMACEUTICALS INDUSTRIES LTD.,
`Petitioner,
`
`v.
`
`MERCK SHARP & DOHME CORP.,
`Patent Owner.
`____________
`
`IPR2020-00040
`Patent 7,326,708 B2
`____________
`
`Record of Oral Hearing
`Hearing Held: February 11, 2021
`____________
`
`
`
`
`Before SHERIDAN K. SNEDDEN, ROBERT A. POLLOCK and
`TIMOTHY G. MAJORS, Administrative Patent Judges.
`
`
`
`
`
`
`
`
`
`
`571-272-7822
`
`
`
`
`Paper No. 90
`Entered: February 25, 2021
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`MYLAN PHARMACEUTICALS INC., DR. REDDY’S
`LABORATORIES, INC., DR. REDDY’S LABORATORIES, LTD., and
`SUN PHARMACEUTICALS INDUSTRIES LTD.,
`Petitioner,
`
`v.
`
`MERCK SHARP & DOHME CORP.,
`Patent Owner.
`____________
`
`IPR2020-00040
`Patent 7,326,708 B2
`____________
`
`Record of Oral Hearing
`Hearing Held: February 11, 2021
`____________
`
`
`
`
`Before SHERIDAN K. SNEDDEN, ROBERT A. POLLOCK and
`TIMOTHY G. MAJORS, Administrative Patent Judges.
`
`
`
`
`
`
`
`
`
`
`
`IPR2020-00040
`Patent 7,326,708 B2
`
`APPEARANCES:
`
`ON BEHALF OF THE PETITIONER, MYLAN PHARMACEUTICALS,
` INC.:
`
`
`JITENDRA MALIK, Ph.D., ESQ.
`Kattan Muchen Roseman, LLP
`550 South Tryon Street
`Charlotte, NC 28202
`
`
`
`ON BEHALF OF THE JOINT PETITIONER, DR. REDDY'S
` LABORATORIES, INC.:
`
`
`RUSSELL W. FAEGENBURG, ESQ.
`Lerner, David, Littenberg, Krumholz & Mentlik, LLP
`600 South Avenue West
`Westfield, NJ 07090
`
`
`
`ON BEHALF OF THE JOINT PETITIONER, SUN PHARMACEUTICAL
` INDUSTRIES, LTD.:
`
`
`CLAIRE FUNDAKOWSKI, ESQ.
`Winston & Strawn, LLP
`1901 L Street
`Washington, D.C. 20036
`
`
`
`ON BEHALF OF THE PATENT OWNER:
`
`
`
`
`
`
`
`
`
`STANLEY E. FISHER, ESQ.
`SHAUN P. MAHAFFY, Ph.D., ESQ.
`Williams & Connolly, LLP
`725 12th Street, N.W.
`Washington, D.C. 20005
`
`The above-entitled matter came on for hearing on Thursday, February
`11, 2021, commencing at 11:00 a.m., EDT, by video/by telephone.
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`Patent 7,326,708 B2
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`
`P R O C E E D I N G S
`- - - - -
`JUDGE MAJORS: We're here today for oral argument in
`
`IPR 2020- 00040 and the related and joined cases, the 1060 and
`the 1072 cases. We've already talked through with counsel for
`Petitioner, Mr. Malik, and Patent Owner, Mr. Fisher and Mr.
`Mahaffy. Do we have counsel on for the joined parties, Dr.
`Reddy's and Sun?
`
`MR. FAEGENBURG: Judge, Russ Faegenburg for Dr.
`Reddy's.
`
`JUDGE MAJORS: Thank you, Mr. Faegenburg. Anyone
`for the Sun parties? Does anyone on Petitioner's part, do you
`know if they were intending to call in or listen in? I know that
`we're also supposed to be having an open line for some interested
`members of the public. I don't know if they're listening in on
`that line and not -- since they're not going to be presenting today
`I just wondered if that's what may be happening.
`
`MR. FAEGENBURG: I provided just a few moments ago
`Sun's counsel with the link I had and with the public audio line
`but I don't know if she's joining.
`
`MR. MALIK: And Your Honor, Mylan hadn't
`communicated with counsel for Sun either so I don't know one
`way or the other either.
`
`JUDGE MAJORS: Since we're going to have a lot of
`people on line today, just to again a preliminary matter. When
`someone is speaking of course try to unmute your line so we can
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`hear you and then for everyone else try to keep your line on mute
`to avoid any ambient noise. That tends to help. We may, it's
`possible given our experience over the last week that we may
`have some technical issues at some point during today's oral
`argument so if that happens just be patient and we'll try to circle
`back and pick up where we left off. Hopefully it doesn't, but if
`it does just sit tight and we'll move everybody back in.
`
`Relatedly, if at any point the parties feel that this video
`format is negatively impacting the ability for them to be heard
`and to make their case, please let us know as well.
`Unfortunately, under normal circumstances we'd want to have
`you in person but these are not exactly normal times so thank
`you again for your patience as the PTAB as well as everybody
`else works through these circumstances. I understand that there's
`a LEAP practitioner. Is that Mr. Mahaffy, you're going to be
`presenting at least part of Patent Owner's case today?
`
`MR. MAHAFFY: That's right, Your Honor.
`
`JUDGE MAJORS: Hold on a second. Telling me to either
`talk quieter or keep my audio down.
`
`MS. FUNDAKOWSKI: I'm sorry, Your Honor. Can you
`hear me?
`
`JUDGE MAJORS: Yes.
`
`MS. FUNDAKOWSKI: Yes. This is Clare Fundakowski on
`behalf of Sun. I was in fact on the public line and of course
`muted. I apologize for that, Your Honor.
`
`JUDGE MAJORS: No, that's okay. I'm glad somebody's on
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`line for Sun. All right. So let me pick back up. So as I think
`folks probably know, Patent Owner's going to get an additional
`15 minutes of time for their arguments by Mr. Mahaffy. Mr.
`Mahaffy, is there an issue or part of the case that you're going to
`focus on or, just trying to figure out what might make sense in
`terms of the overall process here?
`
`MR. MAHAFFY: Yes, Your Honor. I'm going to discuss
`some of the swear behind issues and some of the issues with
`respect to dependent claims as well as some unexpected
`properties. I think I'll let Mr. Fisher speak to this but I think our
`idea was to let Mr. Fisher speak first and for me to take the
`(indiscernible) at the end --
`
`JUDGE MAJORS: Okay.
`
`MR. MAHAFFY: -- of the presentation.
`
`JUDGE MAJORS: Okay. That's fine with us. So as we set
`forth in the oral argument order each side has an hour but as just
`noted, Patent Owner's going to get an additional 15 minutes for
`the presentation by Mr. Mahaffy. You can reserve up to 15
`minutes of your time for rebuttal purposes. We'll start the
`presentations. Petitioner will go first, then Patent Owner and
`then you can reserve rebuttal time. We'll go back and forth with
`that. One other quick note. If the parties could stay on at the
`conclusion of the oral argument just to see if there's any
`questions from the court reporter that can be cleared up that
`would be much appreciated. We'll try to give you -- the panel
`will try to give you advance warning when time is getting short
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`but don't take that as a guarantee, so try to keep track of time
`yourself but we'll try to give you a five minute advance notice of
`when you're running close or when you're into your rebuttal
`time. When speaking please try to identify yourself so that the
`record is clear. We've looked at the record, of course. We have
`access to it and we have your demonstratives so, all that being
`said Petitioner whenever you're ready you can begin.
`
`MR. MALIK: Your Honor, I'd like to reserve 15 minutes
`for rebuttal. So good morning, Your Honors, Jitendra Malik,
`counsel for Mylan and I will be discussing today why the
`challenged claims in Mylan's view are invalid.
`Let's move on to slide 2 and I just want to begin by giving
`Your Honors an overview of what Mylan plans to discuss today.
`I will of course begin by discussing anticipation of claims 1
`through 3, 17, 19, 21 through 23. The focus of the anticipation
`argument is of course W0'498 and '871 and specifically example
`7. Example 7 shows that under its conditions when s itagliptin
`was exposed to HCL, a very strong acid, sitagliptin was only
`formed a 1:1 salt, i.e., a monoprotonated species whereas other
`analogs, when exposed to the same conditions resulted in other
`non 1:1 salt. '871 and '498 also identified using phosphoric acid
`as a particularly preferred acid in the same list as HCL and as
`Dr. Chorghade explained multiple times if HCL can't do it, then
`phosphoric acid won't be able to make it anything other than a
`1:1 salt either under the conditions of Example 7.
`We'll then turn to obviousness and Mylan does think that
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`the claims are anticipated, but if not they would have been
`obvious. As the PTAB noted in pages 15 to 16 of its Institution
`Order, the crux of Mylan's obviousness position still remains
`centered on WO'498. Obviously in connection with obviousness
`we will --
`JUDGE MAJORS: Mr. Malik.
`MR. MALIK: Yes.
`JUDGE MAJORS: Can I interrupt you for just one second?
`Should we -- it seems that the parties have treated the WO
`reference and the '871 patent for all intents and purposes as
`having the same disclosures. Is that fair and should we do the
`same unless you call out something specifically?
`MR. MALIK: Yes, Your Honor.
`JUDGE MAJORS: Okay.
`MR. MALIK: So as it relates to antedation I think the
`parties have come to some agreement that the dispute is
`eventually is governed by In re Huai -Hung Kao, we'll discuss
`that. Then for obviousness we'll talk about the lead compound
`selection specifically based on the Federal Circuit Pfizer and
`Otsuka decisions. Mylan believes that there is no need for a lead
`compound selection in connection with a salt case, so whether or
`not WO'498 has 32 other structures or whether or not there were
`other more promising leads in the prior art, that's not something
`that is relevant in a salt case given the facts here. We believe
`we're under Pfizer as explained further by Otsuka.
`We'll then to claim 4 and again I think the PTAB
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`Patent 7,326,708 B2
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`understood that the thrust of our arguments remain centered on
`WO'498 as page 16 of the Institution Order and its teachings of
`hydrates with minimal use of the Brittain reference just simply to
`show that monohydrates are the most frequently occurring
`hydrates. And then briefly we'll touch on unexpected results.
`As Merck admits in its response on pages 4 to 5 the anhydrous
`1:1 DHP salts were unstable. It had interconversion issues,
`formulation issues such as discolorization, sticking and were
`eventually abandoned.
`As for claim 4, you know, we'll deal with the unexpected
`results but in Mylan's view they are not commensurate in scope
`with claim 4 and Merck has failed to compare it to the closest
`prior art which in this case would be the hydrates of the '498.
`Let's go to slide 4. Slide 4 you see claim 1 which we're
`going to use as a representative to kind of discuss it. This
`effectively is the 1:1 salt of sitagliptin and phosphoric acid. As
`our expert, Dr. Chorghade, explains the dihydrogenphosphate
`salt of sitagliptin is nothing more than the mono- protonated i.e.,
`mono basic amine cation of sitagliptin with its corresponding
`biphosphate anion, i.e., the DHP. In essence you have one side
`the amine and you basically take the most acidic proton of
`phosphoric acid, move it over to the amine, that is the DHP salt.
`Now this is not rocket science. In fact I would direct you to the
`declaration of Vicki Vydra, paragraph 19 and the accompanying
`deposition transcript, pages 36 and 37 where you can see Vicky
`Vydra, a person with six months out of college with a BA in
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`chemistry was able to draw out the DHP salt based on her belief
`of the experiment. So basically, and Vicky Vydra had, Inventor
`Vydra had a skill level well below that of a POSA. Again, this is
`not difficult stuff.
`Go to slide 5. Slide 5 you see claim 15 of WO'498. There
`are other compounds. There are 32 other compounds. Sitagliptin
`is one of them and so we have removed the other compounds and
`claim 15 ends with and pharmaceutically acceptable salts, plural,
`thereof. The reason we drew claim 15 this way is to make it look
`similar to claim 17 of the '871 patent which only has sitagliptin.
`Now Merck wants to spend its time talking about non 1:1
`salts in its analysis completely divorced from the prior art
`disclosures with the goal of presenting this issue to this panel
`that a non-1:1 DHP salt is possible or a non-1:1 salt is possible
`and Merck prevails in rebutting anticipation. But what Merck
`really wants to do is it wants to gloss over three central and
`significant disclosures in WO'498, 1) sitagliptin and its
`pharmaceutically acceptable salts are taught and claimed; 2)
`phosphoric acid is one of seven particularly preferred salts, and
`3) --
`
`JUDGE MAJORS: Eight, right?
`MR. MALIK: -- eight, I'm sorry -- yes, Your Honor, I
`apologize for that. And 3) HCL, a strong reactive (phonetic) in
`phosphoric acids only formed a 1:1 salt with sitagliptin in
`Example 7. Now, the issue here is not to analyze this in a
`vacuum as to whether or not DHP salt is the only phosphoric salt
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`that can form. The issue is whether the 1:1 salt to a POSA is
`necessarily present or the natural result of the element explicitly
`disclosed in the prior art and we will show to the panel that there
`is no doubt that at a minimum not only would a POSA envision
`making the 1:1 salt but in fact Example 7 results in the 1:1 salt.
`So where are we right now?
`JUDGE MAJORS: Can I ask you to pause there for a
`moment? Now, I think you're correct that when you look at
`Example 7 with the hydrochloric acid example it does in that
`example form a 1:1 salt but isn't it the case that in other
`examples with very similarly structured compounds that they
`formed salts of different stoichiometries?
`MR. MALIK: Yes, Your Honor. The other example, let me
`just jump to slide 8, you can see that examples 1, 2, 3, 4 and 5
`did another stoichiometry whereas Example 7 which is sitagliptin
`is a 1:1 stoichiometry and I think Dr. Matzger said at the end of
`the day when you have experimental data, that basically trumps
`all theories. The facts remains is that Example 7 is a 1:1 salt and
`--
`
`JUDGE MAJORS: I'm sorry, Mr. Malik, if I could interject
`again. Just I'm curious because as I understood Petitioner's
`position initially it was that every time you do this reaction with
`phosphoric acid and sitagliptin you're going to get the one
`protonation at the primary amine. This is just a question, I don't
`know if you know the answer or if it's developed in the record,
`but these other compounds that are very similar they must be
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`accepting a proton somewhere else so on the molecule and Patent
`Owner's got a theory about that which I think is the triazol o
`portion of the molecule can accept protons as well. Does
`Petitioner have any position on that and this opinion earlier
`from, is it Dr. Chorghade, that the primary amine can only accept
`the one proton?
`MR. MALIK: In the case of sitagliptin under Example 7
`it's Petitioner's position that that particular molecule as shown
`can only accept a proton on the amine. As far as the other
`compounds, obviously the empirical data shows 2:1 salts,
`Example 6 has a 1:1 salt. I will tell you that when we asked Dr.
`Matzger why it is that Example 7 only showed a 1:1 salt when
`exposed to a thousand-fold excess of HCL, you know, he said no,
`I don't have an opinion on that. His exact words are, "No, I did
`not express an opinion on that." That's at his deposition, line 97,
`5 through 22. The fact remains is Example 7 under the
`conditions present only to the 1:1 and when we asked Dr.
`Matzger his position he said he didn't express an opinion on that.
`JUDGE MAJORS: Let’s put aside the Example 7 for just a
`moment. Petitioner doesn't dispute however that under some
`conditions it is possible to form non-1:1 phosphoric acid salts of
`sitagliptin; right?
`MR. MALIK: Under -- yes, under conditions that are
`completely divorced from the conditions of WO'498 Dr. Matzger
`showed that sitagliptin can do it. But what -- we want to go back
`to slide, sorry, slide 5 really quickly. Where are we right now?
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`What we have is we have a small set of basic compounds one of
`which is sitagliptin and we have a small set of particularly
`preferred compounds, one of which is phosphoric acid
`(indiscernible – audio breaking up) and as the PTAB noted in its
`Institution decision we conclude on the existing record however
`that reasonable minds cannot disagree that WO'498 describes the
`phosphoric acid salt with sitagliptin and this disclosure meets the
`claim limitations. That's on claim 18.
`So the only thing we have to show is whether or not a
`POSA would envision in the 1:1 stoichiometry of 1:1 DHP
`stoichiometry and whether it would be able to make it. I want to
`highlight the last quote on this slide from Dr. Matzger. I want to
`read to the PTAB the full deposition excerpt cited at 146, 13
`through 147, 5.
`"Q. So looking at Example 7 where it disclosed a 1:1 HCL
`salt, can you not clearly see the 1:1 phosphoric acid salt also
`being there as a result of the HCL salt?"
`"A. So by looking at that you can imagine it would exist."
`So Mr. Matzger just envisioned that the claimed 1:1 DHP
`salt from Example 7 1:1 HCL salt and (indiscernible) --
`JUDGE MAJORS: Can I ask you a question about that?
`MR. MALIK: Certainly.
`JUDGE MAJORS: Which slide again were you on, Mr.
`Malik?
`MR. MALIK: I'm on slide 5. Slide 5, Your Honor.
`JUDGE MAJORS: Didn't --
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`MR. MALIK: Yes.
`JUDGE MAJORS: -- didn't Dr. Matzger though continue
`on and almost the very next question you asked him, well, does it
`come to your mind and he said no, it doesn't and that's quite a
`different thing from, you know, having any appreciation that this
`thing is even, the 1:1 salt's even possible?
`MR. MALIK: Well I think that, you know, based on yes,
`Dr. Matzger did hedge a little bit on the following question but
`the fact remains that he also says later on in his deposition as we
`look at that slide, that the WO'498 and '871 claim and teach the
`1:1 salt and we'll see those deposition quotes shortly. So
`assuming that he's envisioning the 1:1 DHP salt under the
`Federal Circuit's In re Gleave , Bristol-Myers Squibb,
`Kennametal and Perricone decisions, all cited in Mylan's
`petition, the only thing Mylan has to do in that case is to show
`that in addition to envisioning the 1:1 DHP salt which Dr.
`Matzger, and for that matter Dr. Chorghade clearly did, that the
`disclosure of the '871 patent and '498 is an enabling disclosure.
`Now, Merck is going to start its presentation by pointing to
`general text divorced from either the '871 patent or the '498 and
`related deposition quotes in the abstract where the salt formation
`is unpredictable. But unpredictability is an obviousness concept.
`This is anticipation. The law only requires an enabling
`disclosure. So the remaining question is assuming Dr. Matzger
`envisions the 1:1 salt as Dr. Chorghade has, the only question is
`is the '871 patent and the '498 enabled to make the 1:1 DHP salt?
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`
`So let's look at the actual facts in the record. Again, bear
`in mind that ground 1 is WO'498 and ground 2 is the Orange
`Book patent, the '871 patent. First of all, Merck has never
`offered an opinion that the 1:1 DHP salt, the anhydrous form, is
`not enabled and either the '871 patent or WO'498. Dr. Matzger
`addressed all claims other than claim 4. Claim 4 was not to Dr.
`Myerson. There is no opinion in Dr. Matzger's declaration of
`any enablement problem with the '871 or '498 or the ones that he
`dealt with.
`Two, Merck put the '871 on the Orange Book for a product
`containing a 1:1 DHP salt. The '871 and '498 have identical
`specifications. Merck has never suggested nor do I believe they
`ever will to suggest that it's Orange Book patent, the '871, does
`not provide an enabling disclosure for the 1:1 DHP salt.
`Three, phosphoric acid is a particularly preferred acid and
`it is routinely used to make the active (phonetic) addition salts of
`APIs. Four, this reaction is simple. It occurs at room
`temperature. The reaction conditions of Example 7 occur at
`ambient indicating no further heat is required and on top of that,
`phosphoric acid and sitagliptin, as the record has showed, are
`both soluble in methanol and Dr. Matzger conceded, as did Dr.
`Chorghade also discussed, that this reaction would be easy to
`run.
`
`Finally, again, the first person to make the 1:1 DHP salt did
`so as part of an automated salt screen (phonetic) with the skill
`level well below that of a POSA. To be clear, Merck has never
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`taken the position that the '871 patent or the '498 patent which
`have the same spec (phonetic) are not enabled for the 1:1 DHP
`salt. Again, putting them on a hydrate thing aside. So assuming
`--
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`JUDGE MAJORS: Doesn't --
`MR. MALIK: Go ahead.
`JUDGE MAJORS: Doesn't the Federal C ircuit tell us that
`enablement is a different question from what's disclosed? Think
`about it -- I'm thinking about Galderma Laboratories v. Teva
`Pharmaceuticals USA which was decided last year where they
`said something to that effect explicitly and so coming back to the
`issue of the 102 and anticipation, I think you have to agree
`certainly there's no express disclosure of a 1:1 DHP salt of
`sitagliptin in the WO reference or the '871 reference.
`MR. MALIK: That is correct. But under In re Gleave,
`Kennametal or Bristol-Myers Squibb the Federal Circuit has said
`that for a reference to be anticipatory there does not have to be
`an actual example within the patent, only that the patent provides
`enabling disclosure.
`JUDGE MAJORS: I may --
`MR. MALIK: The fact that --
`JUDGE MAJORS: -- I may agree with that but what I'm
`wrestling with is the divide between what it means to envision
`something and once envisaged or to envision something and to
`show that something is present in the art as a matter of inherency
`and as I read the Federal Circuit's precedents they say if the
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`thing is not described in the art, you can't just say that the
`skilled person would envisage it and avoid the, you know, strict
`identity test for 102. You'd have to prove inherency, and so I
`guess my question is are you relying on inherency here because I
`-- your papers were not quite clear I guess I'll say on what
`Petitioner was exactly claiming because again from my
`perspective I think you have a problem with the notion of
`envisioning something that's not in any sort of express disclosure
`in the reference itself.
`MR. MALIK: I think what the position of Mylan is is the
`1:1 salt for HCL is there and from that given phosphoric acid is a
`weaker acid than HCL, that the POSA would envision the 1:1
`directly from that. That if HCL can't do it under these
`conditions then neither phosphoric acid. We're looking at a
`significant excess of HCL thousand-fold and despite the fact that
`there's a thousand- fold excess the HCL wasn't -- it wasn't the
`case of sitagliptin to do anything else. Now in the case of --
`JUDGE MAJORS: I'm sorry again, Mr. Malik. I believe it
`was Dr. Matzger, he testified that if you run through all the
`different permutations just taking the 33 compounds and the
`eight preferred acids for forming salts, that you get somewhere
`in the neighborhood of -- and then you started counting for
`stoichiometry differences -- that you get somewhere in the
`neighborhood of I think it was 950 theoretical salts. I didn't see
`that Petitioner ever contested that evidence. Are you aware of
`anything in the record?
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`MR. MALIK: Well, Your Honor, this is where I think we
`focus on In re Gleave where exactly we have two lists here. One
`with the basic compounds and we have the one with the acids and
`In re Gleave I believe if I remember correctly it was 1,000
`compounds and once you have two lists then you can combine
`them. Then it doesn't matter how many compounds you have.
`We're not talking about an In re Petering situation where you
`effectively have to get general ideas and then what do you
`envision. So, you know, I think when you consider In re Gleave
`where you have two exact lists, and even Dr. Wenslow identified
`WO'498 as having two lists; one with the acid, one with the
`amines, that when you combine them you basically have it
`collapses to one list and I think that's laid out in our petition.
`But I do want to address that inherency question a little bit
`more. Again, let me first of all, you know, remind the Court
`again when we asked Dr. Matzger well why is it that when HCL,
`when sitagliptin is exposed to (indiscernible – audio breaking
`up) HCL, why do you only get a mono-protonate species, again
`he had no response to that. He hadn't even addressed that. That
`is the key issue with the WO'498.
`But let's continue on Dr. Matzger's analysis and let's look
`at it. Let's go to slide 10, if you wouldn't mind. So with respect
`to Dr. Matzger, you know, you can see the quote right here. By
`his own admission he effectively was told in connection with this
`matter and his experiments to park his scientific curiosity at the
`door and he basically said, as you can see on the right side, that
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`with respect to WO'498 and '871 he wasn't told to do anything
`with respect to it but rather he was focused on something
`WO'420. As we pointed out in our brief and we started digging
`into this issue a little bit more, Merck starting asserting
`privilege.
`But I do want to point out a couple of statements to the
`PTAB that I think will help to evaluate Dr. Matzger's work. This
`is in Merck's response on pages 17 to 18. They cite the U .S.
`Water Servs., Inc., v. Novozymes A/S case and they say that
`practicing teachings of the prior art reference did not always
`result in the reduction of the deposits. The focus has to be on
`practicing the prior art. WO'498 Example 7, that's where the
`analysis has to start. By his own admission, Dr. Matzger was not
`practicing the prior art. As Dr. Chor ghade said, there's no reason
`to change the conditions whatsoever. Phosphoric acid and
`sitagliptin are soluble in methanol and this would not be a
`difficult situation.
`The other thing I want to point to is what the PTAB said
`essentially the same thing on its footnote 29 in its Institution
`decision and I'll quote,
`"But," -- and again I understand this is the preliminary
`record -- "there is no evidence on the preliminary record to
`suggest that phosphoric acid will donate more than one proton
`under the circumstances relevant here nor that the reaction will
`take place to the exclusion of forming the 1:1 DHP salt."
`The circumstances relevant here are the circumstances of
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`the '871 and the '498, not any possible circumstance, and how do
`we know that Dr. Matzger's work does not represent the
`circumstances relevant here? By his own admission --
`JUDGE MAJORS: Can I stop you again for a second?
`MR. MALIK: Yes, Your Honor.
`JUDGE MAJORS: Let's assume for argument's sake that
`we agree that the testing, the synthesis protocol that Dr. Chyall
`did and that your expert opined on is closer to what's recited in
`Example 7 than what Dr. Matzger did or some of the other
`doctor, I think it was Atwood did, and I'll come back to that in a
`second. But let's just say we agree with you that what you did is
`closer, you have to at least agree though don't you, Mr. Malik,
`that while it may be closer to what was done in Example 7 there
`was still changes that were made. It wasn't just simply swapping
`out HCL for phosphoric acid, there were changes in the protocol
`even from what's explicitly described in Example 7.
`MR. MALIK: Of course, Your Honor. And Dr. Chorghade
`addressed all of the changes, and this is slide 16. If we turn to
`slide 16 that is what Merck said were all the perceived
`differences --
`JUDGE MAJORS: But --
`MR. MALIK: -- the starting material, the active --
`JUDGE MAJORS: -- but again I think that's where it starts
`to get tricky because when you start not only combining a
`phosphoric acid with a sitagliptin and then pointing to Example 7
`and saying okay, we've got to make some changes to
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`accommodate phosphoric acid and by the way we're going to do
`this dropwise addition and do slurry crystallization which is not
`what, as I understand it, it's not what Example 7 did. Now you
`may say that doesn't make a difference but that starts to look a
`lot more like an obviousness rationale than a 102 anticipation
`rationale.
`MR. MALIK: Well, first of all I would point out that Dr.
`Matzger was also aware of all of these results and everything in
`the EX2225, direct you to paragraph 123 and 126 of Dr.
`Matzger's report, I'm sorry, yes, 126 and 123. I think it can -- in
`weighing these experiments you have to consider the fact that
`Merck's own expert didn't opine on any of these. So on one side
`you have Dr. Chorghade offering expert opinion, on the other
`side Merck's own expert wouldn't do it.
`But I do want to point out, perhaps I can put it this way.
`With respect to all of the experimental work that you're exposed
`to, I think one way to look at this is actually one of the cases
`that Merck has in its slides, In re Armodafinil. It's on slide 26,
`and I actually think that it lays out very good framework for the
`PTAB to kind of address all of this and basically it's a Delaware
`case, slide 26, and I suggest that you look at the whole slide, not
`the excerpts that I think Merck provides on that slide.
`What that case basically says is if you take a look at the
`prior art reference, in this case WO'498 and you place the prior
`art parameters in two buckets, the fixed parameters and the
`variable parameters. The variable parameters are the unknown
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`parameters, the fixed ones are where the POSA has to use some
`judgment. The fixed parameters are what bases the prior art
`(indiscernible.)
`Now Merck's slide 29 has ellipses and the ellipses from the
`fourth line on this slide, the ellipses specifically in the '855
`patent does not disclose many details of the procedure. The
`skilled artisans would have to use their judgement to complete
`the experiment.
`So let's take a look at Example 7. What really are the fixed
`parameters? Methanol ambient, excess acid to sitagliptin in the
`Armodafinil case, the variable parameters are what Merck has on
`that slide, cooling rate, ethanol grade and concentration. Dr.
`Matzger did change all the parameters whereas I think Dr. Chyall
`is a lot closer. This is about the salt forming step, it's not about
`removing the blocking groups ancient (phonetic) chemistry,
`whether acid does that. All the experts agree this is about the
`salt forming step. What does sitagliptin do in methanol when
`exposed to phosphoric acid and I certainly think that to the
`extent you want to focus on slurry crystallization, as Dr.
`Chor ghade said the reaction was done with methanol, it was
`never changed. There was no solvent added to co- crystallize.
`That's in slide 16, third box from the bottom. So I certainly
`t
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