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`UNITED STATES PATENT AND TRADEMARK OFFICE
`___________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`____________
`
`CELLTRION, INC., and PFIZER, INC.,
`Petitioner,
`
`v.
`
`GENENTECH, INC.,
`Patent Owner.
`__________
`
`Case IPR2017-01121 (Patent 7,846,441 B1)
`Case IPR2017-01122 (Patent 7,892,549 B2)
`____________
`
`Record of Oral Hearing
`Held: May 18, 2018
`____________
`
`
`Before ZHENYU YANG, CHRISTOPHER G. PAULRAJ, and ROBERT A.
`POLLOCK, Administrative Patent Judges.
`
`
`
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`Case IPR2017-01121 (Patent 7,846,441 B1)
`Case IPR2017-01122 (Patent 7,892,549 B2)
`
`APPEARANCES:
`
`ON BEHALF OF THE PETITIONER, CELLTRION, INC.:
`
`
`CYNTHIA HARDMAN, ESQUIRE
`ELIZABETH J. HOLLAND, ESQUIRE
`Goodwin Proctor LLP
`The New York Times Building
`620 Eighth Avenue
`New York, NY 10018
`
`AMANDA HOLLIS, ESQUIRE
`Kirkland & Ellis, LLP
`300 North LaSalle
`Chicago, IL 60654
`
`ROBERT J. GUNTHER, JR., ESQUIRE
`ANDREW J. DANFORD, ESQUIRE
`STEPHANIE NEELY, ESQUIRE
`NORA Q. E. PASSAMANECK, ESQUIRE
`WilmerHale
`7 World Trade Center
`250 Greenwich Street
`New York, NY 10007
`
`
`
`
`
`
`ON BEHALF OF PETITIONER, PFIZER, INC.:
`
`
`
`
`
`
`ON BEHALF OF THE PATENT OWNER:
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`The above-entitled matter came on for hearing on Friday, May 18,
`2018, at 2:02 p.m, at the U.S. Patent and Trademark Office, Madison
`Building East, 600 Delany Street, Alexandria, Virginia, before Chris Hofer,
`Notary Public.
`
`
`
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`Case IPR2017-01121 (Patent 7,846,441 B1)
`Case IPR2017-01122 (Patent 7,892,549 B2)
`
`
`P R O C E E D I N G S
`JUDGE YANG: Good afternoon. Welcome back. I hope everybody
`enjoyed your lunch. This is again a public hearing for IPR2017-01121 and
`01122 between Petitioner Celltrion and Patent Owner Genentech. The
`challenged patents are 7,846,441 and 7,892,549. IPR2017-02063 filed by
`Pfizer also challenged the 441 patent which is the subject of the 1121 case
`and we previously joined Pfizer in the 1121 case, and counsel for Celltrion
`will argue on behalf both Petitioners. Now counsel, will you please
`introduce yourselves.
`MS. HARDMAN: Good afternoon, Your Honor. Cynthia Hardman
`and Elizabeth Holland of Goodwin Proctor for Petitioner Celltrion.
`JUDGE YANG: Thank you. And Petitioner Pfizer.
`MS. HOLLIS: Amanda Hollis from Kirkland & Ellis. We have
`Benjamin Lasky, Mark McLennan, and a client representative Wendy Hsu
`here, also Mike Dashwood (phonetic).
`JUDGE YANG: Thank you. And the Patent Owner.
`MR. GUNTHER: Your Honor, Bob Gunther from WilmerHale. Mr.
`Danford who's still with me. My colleagues are still with me and Genentech
`representatives are still with me.
`JUDGE YANG: Very good. All right. And everybody was present
`during this morning's argument, so I will not repeat the rules. Each party has
`75 minutes and starting with the Petitioner, would you like to reserve any
`time for rebuttal?
`MS. HARDMAN: Yes, 35 minutes please.
`JUDGE YANG: Thank you. We're ready whenever you are.
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`Case IPR2017-01121 (Patent 7,846,441 B1)
`Case IPR2017-01122 (Patent 7,892,549 B2)
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`
`MS. HARDMAN: Thank you, Your Honor. I'd like to start by
`talking about the Baselga 94 preclinical data. There was a lot of discussion
`at the last hearing that these studies are not reliable and don't --
`JUDGE PAULRAJ: Ms. Hardman, could you speak into the
`microphone a little more?
`MS. HARDMAN: I apologize.
`JUDGE PAULRAJ: I'm having trouble hearing you.
`MS. HARDMAN: I apologize. There was a lot of discussion at the
`last hearing that these data are not reliable and don't lead to a motivation to
`combine trastuzumab with paclitaxel or to a reasonable expectation of
`success.
`JUDGE YANG: Before you go into that Baselga 94 is not a reference
`I guess Petitioner relied on for your ground, I suppose? I think Patent
`Owner points that out a couple of times.
`MS. HARDMAN: You are correct that Baselga 94 is not one of our
`references that is in the instituted ground. However, Baselga 96 is part of
`the instituted ground. Baselga 96 discusses the same preclinical results that
`are in Baselga 94 and there is also Federal Circuit case law, the Genzyme
`Therapeutic v. Biomarin Pharmaceutical case that says that the Board may
`consider references outside of the instituted ground to show knowledge of
`persons of ordinary skill in the art.
`Now if we could please have, Mr. Murphy, Exhibit 2007 displayed on
`the screen. This is Genentech's clinical study protocol. This is their
`amendment where they were adding the paclitaxel arm to their study and if
`we could please turn to page 30 of Exhibit 2007. We see here on page 30 is
`the section 1.4 is captioned Study Rationale and it starts by talking about the
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`Case IPR2017-01121 (Patent 7,846,441 B1)
`Case IPR2017-01122 (Patent 7,892,549 B2)
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`purpose of the study which is to determine whether addition of HER2, that's
`the trastuzumab antibody, would be a valuable addition to standard
`chemotherapy and the only data relied upon in the Study Rationale for the
`addition of trastuzumab into this study with paclitaxel is, in fact, the Baselga
`preclinical data. We can see in the highlighting it says,
`"In vivo nude mouse xenograft models using HER2 transfected cell
`lines have demonstrated an additive effect in reducing tumor volume when
`rhuMAb HER2 is given in combination with doxodoxorubicin compared
`with rhuMAb, HER2 or doxodoxorubicin given alone," and it has some
`citations.
`It then goes on to say,
`"Similar findings using a different in vivo model were reported with
`rhuMAb, HER2 and paclitaxel," and it has citations references 21 and 23
`which we'll get to in a moment.
`It goes on to say,
`"It is anticipated that in a population of patients with HER2 over
`expressing metastatic breast cancer, the addition of rhuMAb HER2 to
`citotoxic chemotherapy will enhance efficacy," and if you could show us
`please the references 21 and 23 which occurred later in the document we can
`see here that reference 23 is in fact Baselga 94 which is marked in this IPR
`as Exhibit 1019. So in fact --
`JUDGE YANG: Judge Pollock, we can hardly hear you. Can you
`repeat what you asked for.
`JUDGE POLLOCK: I'm not able to follow your argument because I
`can't see the slide (indiscernible) the particular pages.
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`Case IPR2017-01121 (Patent 7,846,441 B1)
`Case IPR2017-01122 (Patent 7,892,549 B2)
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`
`JUDGE YANG: Yes. Would you please point out where you are at
`exactly because Judge Pollock cannot see the screen and he hasn't been able
`to follow you.
`MS. HARDMAN: Yes, Your Honor. I apologize and I'm sorry for
`speaking over you. I didn't realize that you were speaking on the telephone.
`It's difficult to hear you. We are looking at Exhibit 2007 and page 30 of that
`exhibit, and specifically Section 1.4, and we were then looking at the
`references that are cited on page 30 and those show up on page 64 of Exhibit
`2007, and what we're showing here is that the references that Genentech
`relied on as the sole basis for the Study Rationale of adding the combination
`of trastuzumab and paclitaxel into this study is, in fact, the Baselga
`preclinical study that we heard a lot about in the last hearing is not reliable
`and would not lead to motivation of success.
`So that's their litigation position here, but as you can see if we go back
`please to the Study Rationale on page 30 they in fact told the FDA that it is
`anticipated based on these preclinical results that the addition of rhuMAb
`HER2 to cytotoxic chemotherapy will in fact enhance efficacy.
`JUDGE POLLOCK: Thank you.
`MS. HARDMAN: Now, and when they're talking about efficacy what
`they were testing in this clinical study is in fact the end point of this study
`was extension of time to disease progression. So here they're telling the
`FDA that these preclinical studies are in fact correlating with extension of
`time to disease progression.
`Now, if we could turn please to slide 4. Just stepping back to the
`grounds that were instituted on the claims of the 441 patent, there are three
`references; the Baselga 96 reference which we heard a lot about at the last
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`Case IPR2017-01121 (Patent 7,846,441 B1)
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`trial, Seidman 1996 which, as we'll talk about, discusses paclitaxel and its
`efficacy in HER2 positive metastatic breast cancer patients, and the taxol
`PDR which is the drug label for the approved drug taxol which
`demonstrates, among other things, known dosing schedules and dosing
`amounts for paclitaxel that were in the prior art.
`Slide 7 please. Now Baselga 96, again we heard a lot about this so I
`won't belabor it but this was a phase two clinical study. It used trastuzumab
`as a single agent in HER2 positive patients. It concluded that the median
`time for progression for patients with either minor or stable disease was 5.1
`months and the article characterized this as an unusually long duration of
`minimal response in stable disease. So what this article was teaching a
`person of skill in the art was that trastuzumab alone would be expected to
`result in an unusually long duration of minimal in stable disease in HER2
`positive patients. Mr. Gunther –
`JUDGE YANG: Okay. I think you are moving towards what the
`question I am going to ask. Mr. Gunther in the morning said this 5.1 is only
`for a very small group of patients. Can you address that point?
`MS. HARDMAN: Yes, Your Honor. There were in fact some non-
`responders in some patients in the study who did not have this lengthy
`extension. However, there were I think it was at least 11 patients who did
`have this median extension of 5.1 months and in this disease that HER2
`positive patients where it was a very dire prognosis for any patient, I think
`having even this sub-population of people that respond so remarkably well
`to this drug would be something POSAS would be interested in and
`motivated to replicate for other patients in the sub-population that would
`respond well.
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`Case IPR2017-01121 (Patent 7,846,441 B1)
`Case IPR2017-01122 (Patent 7,892,549 B2)
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`
`Slide 8, please. The Baselga 96 reference also taught POSAS a lot
`about the safety of trastuzumab. It has a lot of quotations talking about the
`drug was remarkably well tolerated. It says there was an absence of
`significant toxicity, that's on page 741 of the reference. It reports that there
`was only one severe adverse event out of 768 administrations of the drug
`that were given over the course of the clinical study. That is in table 3 of the
`reference on page 740.
`Now, Baselga 96 is not the only reference in the prior art that talks
`about the administration of trastuzumab in human patients. There is also the
`Pegram 1995 reference which we cited in our petition, that's Exhibit 1022,
`and that was a Phase II clinical study of trastuzumab in combination with
`cisplatin and that reference also reported that trastuzumab had no substantial
`toxicity in the combination with cisplatin. It also talked about the results of
`Phase I clinical studies. These were dose escalation studies and Pegram
`1995 reported that trastuzumab had no substantial toxicity at any dose levels.
`So, in summary from these references, a POSA would have known that
`trastuzumab had been demonstrated to have efficacy as monotherapy in
`HER2 positive patients and was reported to be really quite safe with few
`serious adverse events.
`If we could have slide 10, please. Now, as Dr. Earhart, that's
`Celltrion's expert, explained in his declarations at the time of the priority
`date POSAs knew that cancer was more effectively treated with a
`combination of agents rather than monotherapy and he explained that this
`knowledge would have motivated POSAs to combine trastuzumab with
`another agent to get a more effective therapy and, in fact, Baselga 1996 itself
`touches on combination chemotherapy. As we saw earlier it talks about not
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`Case IPR2017-01121 (Patent 7,846,441 B1)
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`only preclinical studies of combinations of trastuzumab with other agents,
`but it also reports that human clinical trials of trastuzumab in combination
`other agents were already underway.
`Slide 9, please. Now, in terms of what agents a POSA would have
`looked at to potentially combine with trastuzumab, Dr. Earhart talked about
`the concept of tntratumor heterogeneity and this means that POSAs knew
`that tumors in HER2 positive patients contained a variety of different types
`of mutations, so even in HER2 positive patients only a subset of the cells in
`that tumor would be HER2 positive and there would be other varieties of
`mutation that would respond to other agents as well and this is why
`combination therapy is known to be so effective. Dr. Earhart testifies that a
`POSA would have been motivated to select an agent with broad efficacy
`against all types of metastatic breast cancer and not just HER2 positive
`cancer.
`Slide 11, please. Now, a POSA's choice of what agent to use in
`combination would have been guided by four principles of combination
`chemotherapy. These were a well established paradigm used by POSAs in
`the prior art for rationalizing combination chemotherapy treatments and as
`Dr. Earhart explains in referencing here slide 11, a POSA would look for
`agents with different resistance mechanisms and this is so that the agents
`would be as effective as possible against all the different types of mutations
`that would be found in a particular tumor. POSAs would look for single
`agent efficacy of each of the agents alone in the target population. They
`would look for different mechanisms of action for the two agents and they
`would look for non-overlapping toxicities.
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`Case IPR2017-01121 (Patent 7,846,441 B1)
`Case IPR2017-01122 (Patent 7,892,549 B2)
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`
`JUDGE YANG: So, Patent Owner challenged here I believe that
`these principles primarily apply to I guess chemotherapy and here we are
`talking about a monoclonal antibody which was new at the time. Can you
`address that please?
`MS. HARDMAN: Yes, Your Honor. Could we turn to slide 19,
`please. So you are correct. Patent Owner has made that allegation. But in
`fact Patent Owner's expert, Dr. Tannenbaum testified that she's actually not
`aware of any reason articulated in the prior art as to why these four
`principles should not apply to the combination of chemotherapeutic agents
`and antibodies, and also there was already a combination, let's not forget, of
`trastuzumab with cisplatin which was already a traditional chemotherapy
`agent already taught in the prior art. I would also add that Patent Owner has
`not identified any incompatibilities in the properties of either trastuzumab or
`paclitaxel that would make them incompatible in combination.
`Could we have slide 22, please. Now, Patent Owner asserted that
`there was no evidence of POSAs having actually applied these four
`principles of combination therapy to a combination of antibody and
`chemotherapy and this is a pretty curious assertion because Genentech itself
`actually used very similar principles as a rationale to add the antibody which
`later became known as Rituxan, into a traditional chemotherapy regimen
`called CHOP, it's an acronym C-H-O-P, and on slide 22 we have a quote
`here from Exhibit 1101 which is a prior art publication that dates back to
`1995 and here this abstract that is shown in Exhibit 1101 is talking about a
`clinical study that Genentech performed with its partner at the time called
`IDEC. They were combining the Chimeric antibody known as T2B8 which
`again later became known as Rituxan together with CHOP and you can see
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`Case IPR2017-01121 (Patent 7,846,441 B1)
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`from the quote here on slide 22 that their study rationale for combining these
`two agents used very similar principles to the four principles that Dr. Earhart
`said a POSA would have applied to the combination of trastuzumab and
`chemotherapy. Such just calling out here on the slide they call out single
`agent efficacy, they call out non-cross-resistance mechanisms of action, they
`call out synergy with chemotherapeutic agents and also non-overlapping
`toxicity. So again very similar to the four principles Dr. Earhart used that
`Patent Owner was trying to say only apply to chemotherapy. Here they're
`being applied by Genentech itself to a regimen of antibody with
`chemotherapy.
`Slide 15, please. Now, Dr. Earhart testified that using these four
`principles a person of ordinary skill in the art would have identified
`paclitaxel as an agent for the combination with trastuzumab and remember
`that as of the priority date here, paclitaxel had been on the market. It was an
`approved drug. In fact we were just looking at the study rationale and
`Genentech reference it as one of the standard chemotherapeutic agents. As
`Dr. Earhart testified, paclitaxel would have made a good choice. It was
`FDA approved for metastatic breast cancer. It had an approved dosage
`schedule that was known for metastatic breast cancer patients and that's set
`forth in the taxol PDR Exhibit 1012.
`Slide 14, please. Now paclitaxel was a good choice, not only because
`it was approved for metastatic breast cancer, but also because it was reported
`to be effective against the sub-population of metastatic HER2 positive
`patients, and this information comes from an abstract that is marked as
`Exhibit 1011, that's the Seidman 1996 abstract. Now, Seidman 1996 itself
`does not report the results of a clinical study, rather what the authors in
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`Case IPR2017-01121 (Patent 7,846,441 B1)
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`Seidman 1996 did was look back at stored tissue samples and these tissue
`samples came from metastatic breast cancer patients who had participated in
`Phase II studies of paclitaxel and docetaxel. docetaxel is another type of
`taxoid, in the same class as paclitaxel.
`So at the time of those Phase II studies it hadn't been determined,
`nobody looked to see whether these patients were HER2 positive. But
`Seidman and company decided retrospectively let's look back at those tissue
`samples of people who were treated, determine if they were HER2 positive
`and see how if there's any difference in whether HER2 positive patients
`reacted to paclitaxel differently than HER2 negative patients, and so when
`they did that analysis they found as shown here on slide 14 that 58.8 percent
`of the HER2 positive patients responded to the treatment paclitaxel whereas
`only 38.7 percent of patients who were not HER2 positive responded to that
`same treatment, and so they concluded that HER2 positive over expression
`in metastatic breast cancer seems to conver sensitivity rather than resistance
`to Taxanes.
`So on slide 13, please, given that paclitaxel had demonstrated efficacy
`both in metastatic breast cancer and the Seidman suggestion that it would
`also be useful in HER2 positive breast cancer, these made it a good choice
`for a combination with trastuzumab.
`Now could we call up please Exhibit 1019, and if we could go to page
`4 of Exhibit 1019, please. This is an abstract by Baselga and others
`reporting on some work done on trastuzumab alone and in combination with
`chemotherapy in Xenografts, and this abstract underscores the motivation to
`combine trastuzumab and paclitaxel. The last sentence here talks about, or
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`the last two sentences we can see starting in the abstract 53 in the top left
`corner. Yes, thank you. It's the last two sentences here say,
`"In summary, anti-HER2 MAbs can eradicate well established tumors
`and enhance the activity of paclitaxel and doxorubicin against human breast
`cancer xenografts. Clinical trials are underway."
`So this is telling POSAs that in fact other people have already pursued
`the combination of trastuzumab and paclitaxel in human patients, which
`again underscores the motivation.
`I think you'll hear from Patent Owner that despite what this and other
`references like it clearly say about clinical trials being underway of the
`combination of trastuzumab and paclitaxel, that in fact they weren't
`underway yet because the protocol had not yet been amended, but of course
`the timing of the protocol amendment is confidential information to
`Genentech. They haven't asserted that people of ordinary skill in the art
`would have known this, so based on the information publicly accessible and
`available to POSAs, the indication was that these clinical trials in fact were
`already underway.
`Can we have slide 18, please. This is just a summary of the evidence
`of the record showing that the combination of trastuzumab and paclitaxel in
`fact meets the four principles of combination therapy that Dr. Earhart talked
`about. As he demonstrates, they had single agent efficacy in human patients
`with HER2 overexpressing breast cancer. They had non-overlapping
`toxicities, different mechanisms of action and non-overlapping resistance
`mechanisms, and actually Patent Owner's expert although she disputed the
`applicability of the four principles of combination therapy, she disputed that
`they would apply to a combination that includes an antibody, she did in fact
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`agree that the combination of trastuzumab and paclitaxel would in fact
`satisfy those four principles and that you can find in her deposition transcript
`at Exhibit 1052, page 90, line 8 through page 91, line 2.
`Can we have slide 27, please. Now we think that actually, as Dr.
`Earhart testified, the single agent efficacy of each of these agents and the
`fact that they satisfy the four principles of combination therapy is sufficient
`alone to motivate the combination. Nevertheless, there was a lot of
`indication in the prior art that based on preclinical studies that this
`combination would be something that POSAs should try. On slide 27 we
`show a quote from Seidman 1995, that's Exhibit 1010, and those authors talk
`about the striking anti-tumor effects shown when paclitaxel and trastuzumab
`were combined in xenografts with no increased toxicity.
`Slide 25, please. This is again the Baselga abstract 53, Exhibit 1019,
`and this showed that the combination with paclitaxel outperformed
`doxorubicin and also remarks that it did not increase the toxicity of
`paclitaxel, and we don't have to call it up but slide 26 is similar. That
`reference is Baselga abstract 2262 which has very similar disclosure.
`Now, if we could have slide 28, please. I would just like to touch
`briefly on the claim limitation in the absence of an Anthracycline limitation.
`As the Board found in its institution decision in IPR2017-00731, this
`limitation was satisfied by an antibody paclitaxel combination that does not
`include an Anthracycline derivative and for the reasons discussed, the prior
`art motivated a combination of antibody with paclitaxel and the motivation
`that got us to that combination did not suggest that an Anthracycline must
`necessarily be included in that combination, so this satisfies that this claim
`limitation in the absence of an Anthracycline derivative.
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`Case IPR2017-01121 (Patent 7,846,441 B1)
`Case IPR2017-01122 (Patent 7,892,549 B2)
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`Nevertheless, there are good reasons that POSAs had for specifically
`avoiding Anthracyclines in combination. It was known that Anthracyclines
`had issues with cardio toxicity. It was known that there was a lifetime limit
`on dose of Anthracyclines. So for patients who had already received
`Anthracyclines but still needed further treatment there was a motivation to
`avoid giving more Anthracycline in those particular patients.
`Slide 29, please. It was also known that some patients were resistant
`to Anthracyclines and meanwhile paclitaxel was known to have utility in
`patients who were Anthracycline resistant, so there's good reason when you
`have paclitaxel in a combination to avoid including Anthracycline at least
`for that sub-population of patients who were known to be resistant and
`would not get any benefit from inclusion of Anthracycline.
`Slide 2, please. Patent Owner has put much stock in the limitation of
`the extending the time to disease progression without increasing the overall
`severe adverse events. But if you look at the full limitation, those limitations
`are pegged to an amount effective to extend the time to disease progression
`without increase in overall severe adverse events, so the claims don't per se
`require these claimed efficacy and safety outcomes. What it's talking about
`is administering an amount that's effective to achieve these and as Dr.
`Earhart explained, a POSA would have been motivated to administer the
`known dosing amounts in the prior art and these known dosing amounts
`Patent Owner has not disputed that once you give those known dosing
`amounts, that would be an amount effective to achieve these actual clinical
`safety and efficacy parameters.
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`Case IPR2017-01121 (Patent 7,846,441 B1)
`Case IPR2017-01122 (Patent 7,892,549 B2)
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`JUDGE YANG: What about the severe adverse event, that limitation,
`is it also attached to the amount or looking at the slide it looks as if you are
`saying that's an independent limitation?
`MS. HARDMAN: I think the spacing was just done just to highlight
`the different types of limitations. I think the overall increase in severe
`adverse events is also tagged to the amount effective.
`JUDGE YANG: Okay. I don't know if you're going to go into it, but
`at some point can we take some time to address this limitation specifically,
`the overall severe adverse events part? You can address it whenever.
`MS. HARDMAN: Yes. In terms of the Motion to Amend or --
`JUDGE YANG: No. Well, let's start with the claim construction part.
`First, do you agree with the NCI's definition of the adverse event? Patent
`Owner agrees. They very much agree, I get that part. Do you agree with
`that?
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`MS. HARDMAN: Not specifically, no because, for example, the NCI
`definition -- (to counsel) do you have Exhibit 3001? Well, okay, the NCI
`definition has there in part a statement that an adverse event is an
`unexpected medical problem. I think though this is inconsistent with the
`specification of the patent. These patents suggests that myocardial
`dysfunction, for example, is an adverse event but that was a known problem
`before the patent that was associated with Anthracyclines. So right there,
`you know, this definition I don't think is quite applicable because it's
`inconsistent with the patent in that regard.
`JUDGE PAULRAJ: But was it unexpected with respect to the
`combination?
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`Case IPR2017-01121 (Patent 7,846,441 B1)
`Case IPR2017-01122 (Patent 7,892,549 B2)
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`MS. HARDMAN: Patent Owner has contended that when they put
`the antibody together with Anthracycline they got an unexpected amount of
`cardio disfunction, myocardial dysfunction.
`JUDGE PAULRAJ: So isn't that where the unexpectedness comes
`from in this context?
`MS. HARDMAN: But it doesn't -- I think the myocardial dysfunction
`was also pegged to the Anthracycline administrations alone and that it was
`logged there as an adverse event, when they were just administered the
`Anthracycline derivative along and Anthracyclines before their patent were
`already known to result in an issue of myocardial dysfunction, so it's not
`unexpected with respect to at least the single agent administration. But
`talking about claim construction, if we could have slide 30.
`JUDGE PAULRAJ: Actually, Ms. Hardman, could you go back to
`the last slide that you had about the amount, the argument that you're making
`(indiscernible.)
`MS. HARDMAN: Slide 2, please. We were looking at the claim.
`JUDGE PAULRAJ: Yes. So if I understand your point, is that the
`prior art already taught administration of certain amounts of the taxoid and
`certain amounts of the antibody, so if you applied those amounts -- is it an
`inherency argument that you're trying to reach, asking us to make?
`MS. HARDMAN: Yes. I think it would be an inherency argument.
`The amounts that were known in the prior art, if administered to a patient
`which is what Dr. Earhart is saying a POSA would have been motivated to
`do, that results in the claim's efficacy and safety parameters.
`JUDGE PAULRAJ: But the claim here specifically talks about an
`amount, and I read that as an amount of the combination. So are we to
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`Case IPR2017-01121 (Patent 7,846,441 B1)
`Case IPR2017-01122 (Patent 7,892,549 B2)
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`interpret an amount as the individual amounts of each of the separate drugs
`that are going to be administered in this part of the combination?
`MS. HARDMAN: Yes. I think it would be the amount of the single
`agent on the one hand and the amount of the single agent on the other.
`Those together would be the amount effective to extend the time, et cetera.
`JUDGE PAULRAJ: So just to be clear then, so the prior art taught
`amount X for the taxol and then amount Y for the antibody, so when you
`read an amount here you're talking about an X plus Y?
`MS. HARDMAN: Yes. And those amounts were known in the prior
`art. Just briefly touching on the Motion to Amend -- no, I'm sorry. Let me
`stick with claim construction for a moment. Slide 30. The Board of course
`construed the claims in connection with the disclaimer made during
`prosecution and we believe that's a correct statement. When our expert, Dr.
`Earhart, read the prosecution history he also read the disclaimer consistent
`with the result recognized by your Honors which is different than Dr.
`Tannenbaum's reading which I think probably strains credibility a little bit.
`So we think that the claim construction that you have adopted is correct.
`They made that disclaimer during prosecution and the public is entitled to
`rely on it.
`Dr. Earhart did also talk about claim construction based solely on the
`specification and there he, looking at the specification, he found that the
`correct comparator is paclitaxel alone because that's what's discussed in the
`specification. But he wasn't making the legal determination of whether a
`disclaimer should actually apply and we do believe that the disclaimer
`actually should apply.
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`Case IPR2017-01121 (Patent 7,846,441 B1)
`Case IPR2017-01122 (Patent 7,892,549 B2)
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`Just briefly touching on the 541 patent. If we could have slide 5,
`please. The 549 patent, the claims are a little bit different and adds a third
`agent. It's a combination of trastuzumab, taxoid and a further growth
`inhibitory agent. The grounds are similar but there's one additional
`reference, that's the Pegrum 1995 reference, and that discloses as I
`mentioned before a combination of trastuzumab and cisplatin in HER2
`metastatic breast cancer patients in a Phase II study. Patent Owner really
`hasn't argued that the addition of the further growth inhibi