UNITED STATES PATENT AND TRADEMARK OFFICE
`_____________
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`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`_____________
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`GENOME & COMPANY,
`Petitioner,
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`v.
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`THE UNIVERSITY OF CHICAGO,
`Patent Owner.
`_____________
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`Case PGR2019-00002
`Patent 9,855,302 B2
`_____________
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`Record of Oral Hearing
`Held: January 15, 2020
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`_____________
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`Before SHERIDAN K. SNEDDEN, SUSAN L.C. MITCHELL, and
`JOHN E. SCHNEIDER, Administrative Patent Judges.
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`_____________
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`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`_____________
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`GENOME & COMPANY,
`Petitioner,
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`v.
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`THE UNIVERSITY OF CHICAGO,
`Patent Owner.
`_____________
`
`Case PGR2019-00002
`Patent 9,855,302 B2
`_____________
`
`Record of Oral Hearing
`Held: January 15, 2020
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`_____________
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`
`Before SHERIDAN K. SNEDDEN, SUSAN L.C. MITCHELL, and
`JOHN E. SCHNEIDER, Administrative Patent Judges.
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`Case PGR2019-00002
`Patent 9,855,302 B2
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`APPEARANCES:
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`ON BEHALF OF THE PETITIONER:
`
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`JOHN A. BAUER, ESQUIRE
`MINTZ, LEVIN, COHN, FERRIS GLOVESY AND POPEO, P.C.
`701 PENNSYLVANIA AVENUE NW,
`Suite 900
`WASHINGTON, DC 20004
`202-434-7399
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`
`
`ON BEHALF OF THE PATENT OWNER:
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`SCOTT E. KAMHOLTZ
`COVINGTON & BURLING LLP
`ONE CITYCENTER
`850 10TH STREET, NW
`WASHINGTON, DC 200001
`202-662-5339
`
`
`
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`The above-entitled matter came on for hearing on Wednesday,
`January 15, 2020, commencing at 1:00 p.m., at the U.S. Patent &
`Trademark Office, 600 Dulany Street, Alexandria, Virginia 22314.
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`Patent 9,855,302 B2
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` (Proceedings begin at 1:00 p.m.)
` JUDGE MITCHELL: You may be seated.
` So good afternoon, everyone. We have a final
`hearing this afternoon in PGR2019-00002. I am Judge Mitchell,
`and seated to my left is Judge Snedden, and with us by video
`conference, is Judge Schneider.
` I would like to get appearances for the parties on
`the record. So who do we have for Petitioner?
` MR. BAUER: Good afternoon, Judge. My name is John
`Bauer. I'm here for Petitioner, lead counsel. I'm also here
`with Andrew Schultz and I'm also here with Kongsik Kim, and
`we're from the law firm of Nelson Mullins.
` JUDGE MITCHELL: Hi.
` MR. BAUER: And we filed the case. How -- myself
`and Kongsik's subordinates.
` JUDGE MITCHELL: All right. Thank you and welcome.
` MR. BAUER: Thank you.
` JUDGE MITCHELL: And who do we have for Patent
`Owner?
` MR. KAMHOLTZ: Scott Kamholtz, lead counsel for
`Patent Owner. I'm joined by Jennifer Robbins, patent
`consultant.
` JUDGE MITCHELL: All right. Thank you and welcome.
` We certainly set forth our procedure for how we're
`going to handle the oral hearing today in our order, but I
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`just wanted to emphasize a couple of things with you before we
`get started.
` Each of you, as we said in our order, will have one-
`hour total time to present argument per side. And to assist
`Judge Schneider in following along with your argument and for
`the clarity of the record when we go back and take a look, it
`is very important that if you refer to an exhibit, that you
`state the exhibit number and the page number to which you are
`referring. And when you're referring to a demonstrative, that
`you state the slide number.
` Petitioner has the burden of showing the
`unpatentability of the challenged claims and the Petitioner
`will go first, and certainly, may reserve time for rebuttal.
`The Patent Owner will then have the opportunity to present its
`response and may reserve some time for rebuttal also.
` We have reviewed Petitioner's Notice of Objections
`to the Patent Owner's demonstrative exhibits. We're not going
`to exclude any demonstrative at this time, but Petitioner may
`certainly address any objectionable demonstrative in its
`argument if you choose.
` Furthermore, we just wanted to emphasize that
`demonstratives are not evidence and we won't consider them as
`such. They are used for the benefit of those in this room and
`for the benefit of the transcript that will become a part of
`this public record. The panel will distinguish evidence in
`the record from argument appearing in the demonstrative
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`exhibits and all arguments must be supported by evidence
`already of record and relied on in the briefing. The panel
`will not consider arguments or evidence appearing only in
`demonstrative exhibits.
` So, Petitioner, you are welcome to begin, and would
`you like to reserve time for rebuttal?
` MR. BAUER: Yes, Your Honor. I would like to
`reserve 20 minutes for rebuttal.
` JUDGE MITCHELL: All right. Thank you.
` MR. BAUER: Good afternoon, Judge Mitchell, Judge
`Snedden, Judge Schneider. I represent the Petitioner in this
`case. And may I approach? I have two subsequent
`demonstratives for you.
` JUDGE MITCHELL: Certainly.
` MR. BAUER: Basically, just to give some framework
`as to the argument that I'm going to present in the opening.
`First, it will be just a general introduction with respect to
`what the patent is about. And then I'll say a couple of words
`about our expert, Dr. Braun. And then I'll address
`obviousness --
` JUDGE SCHNEIDER: Counsel, I'm sorry. I can barely
`hear you. Could you adjust the microphone a little bit? Just
`--
` MR. BAUER: Is that better, Judge.
` JUDGE SCHNEIDER: Yeah. That's better. Let's see.
` MR. BAUER: I got to be careful with that. Is this
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`better?
` JUDGE SCHNEIDER: That's much better. Thank you.
` MR. BAUER: Okay. So to repeat, just to give a
`framework as to how I'm going to present the argument today.
`Originally, though, I'll start off with just a brief
`introduction of what the patient is about, some words about
`the qualification of our expert. And then address obviousness
`and then address enablement.
` So the patent is basically a method of treating
`cancer in a human. If we go to now, Demonstrative Slide 3,
`where you can see Claim 1 has been pasted in from Exhibit
`1001. And the claim, basically, has, essentially, three
`elements. It's a method of treating cancer in a human, number
`one. Number two, co-administering an immune checkpoint
`inhibitor. And number three, co-administering the bacteria
`from the genus Bifidobacterium.
` I may, during the hearing, shorten Bifidobacterium
`to be just Bifido. It's easy to pronounce and I just want to
`give the Court -- is that okay with the Court?
` JUDGE MITHCELL: Sure.
` MR. BAUER: Okay. Thank you.
` JUDGE SCHNEIDER: No problem.
` MR. BAUER: So if we take a look -- a closer look at
`the claim, it's a method of treating cancer. And then if we
`go to Demonstrative Slide 4, you can see that the Patentee
`broadly defined cancer in the specification. And you can see
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`that Exhibit 1001 from Columns 28:54, through 32:44, the
`Patentee listed 165 disorders and 22 broad categories of
`cancer. It's quite broad. It is a long laundry list of the
`cancers that are, supposedly, be able to be treated within the
`scope of the claims.
` If we then turn to Demonstrative Slide 5, that's
`just a continuation of the Patentee's listing of cancers that
`are, allegedly, can be treated by the method of the claimed
`invention.
` If we then go to Slide Number 6, we go to the second
`element of the claim. It's the checkpoint inhibitor. And I
`just want to broadly say -- or briefly say that the immune
`checkpoint inhibitor is broadly defined. If we look at the
`right-hand column in the Petitioner demonstrative at Column 5,
`Lines 14 to 20, it can be a polypeptide or a protein. And it
`just needs to bind to the checkpoint. It also can be an
`interfering nucleic acid.
` I'll come back more to the scope of the checkpoint
`inhibitor when we address enablement, but I just did want to
`say that it's quite broad and it's claimed functionally.
` If we then go to the third element, briefly, it's
`the Bifidobacterium. The Bifido is claimed, once again, quite
`broadly. It's the genus, but Dependent Claim 4 lists 36
`species. And the last one is Bifidobacterium sp, which is a
`yet to be discovered Bifido.
` So we can see that the claim is broad. And if we
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`then take a look at Slide Number 8, we contrast the broad
`scope of the claims with the disclosure of what's in the '302
`Patent. And we find that the disclosure is quite narrow.
`There's only two cancers of which are treated in the Patent,
`melanoma and bladder. One checkpoint inhibitor, an alphaPD-L1
`antibody.
` And the Bifido there is, basically, some -- a couple
`of experiments in a mouse. One of which is, basically, they
`used the feces of one and transferred it to another. And then
`they analyzed the feces and they said that it had under 16
`SRNA and an increased amount of Bifido.
` And then they have a cocktail of these four
`different species of Bifido. And that's it. So it's a broad
`claim and a narrow spec. And that was acknowledge by the
`Board in their institution decision and the request for
`reconsideration.
` I just want to say -- also, transition to
`Petitioner's expert, Dr. Braun. Patent Order has taken a
`number of shots at Dr. Braun in the Motion to Exclude and also
`in the briefing, reportedly, alleging that Dr. Braun is not
`qualified. I just want to say that, first of all, if we take
`a look at Slide Number 9, that Dr. Braun had a Ph.D. in
`Immunology from Stanford and an M.D. from Harvard Medical
`School.
` And then if we go to Paragraph 7 of Exhibit 1002,
`which is Dr. Braun's expert report, I'm -- or his declaration,
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`it tells you that from 1991 to 2018, he was the co-Director
`and Director of the Tumor Immunology Program for the UCLA
`Jonsson Comprehensive Cancer Center.
` So in terms of the technology at issue in this case,
`the immune checkpoint inhibitors and probiotics, mainly
`Bifidobacterium, it is precisely in Dr. Braun's wheelhouse.
`And if we then go to Slide Number 10, this is basically --
`this is telling the Board that, not only does he have
`experience, but he also has active clinical experience in
`terms of prescribing medications to cancer patients. And
`that's shown in Paragraph 12, where he intimately and is
`regularly involved in phases of management of cancer patients.
` Patent Owner, through precisely narrow questions,
`asked Dr. Braun if he was the one who actually administered
`the checkpoint inhibitor, or he was the one who actually did
`that. That's not Dr. Braun's responsibility. That may be a
`nurse. But it's very clear, if we then turn to Slide Number
`11, that because he's a pathologist.
` And if we go to under his deposition, which is in
`Slide Number 11, the last part of the quote, Exhibit 2078 from
`10:24 to 11:9, he basically says, quote, "So I've been
`regularly involved in all phases of the management of cancer
`patients."
` So there is more, if we go to Slide Number 12, where
`there's additional Braun testimony cited. Exhibit 2078, 34:2
`to 20 and Exhibit 2078, 11:20 to 23, where it shows that Dr.
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`Braun is involved in the choices and oversees methods of
`treating cancer patients. That's part of his job. So we
`clearly believe that Dr. Braun is highly qualified to opine on
`the subject matter of this case.
` Now --
` JUDGE MITCHELL: So Dr. Braun actually treated
`patients?
` MR. BAUER: Correct.
` JUDGE MITCHELL: Okay.
` MR. BAUER: If you look at his -- he oversaw the
`treatment of them.
` JUDGE SCHNEIDER: Well, I think they're also -- I
`think looking at Slide 12 at the bottom there, it said, "I
`have directly prescribed and administered therapy to patients
`to treat cancer, yes."
` MR. BAUER: Yes, that's right.
` So turning to the obviousness part of the case, let
`me just briefly say, sort of, the theme of Petitioner's
`obviousness side of the case. You've got a method of treating
`human cancer, which is as broad as the day is long. And you
`then administer, according to the claim, a checkpoint
`inhibitor and a Bifido.
` What was shown in the prior art is that from the
`checkpoint inhibitor, Korman show that you could use a CPI and
`treat colon cancer or fibrosarcoma. And there's no dispute
`about what the scope of Korman is. In fact, (indiscernible)
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`makes no allegation that he's an inventor of checkpoint
`inhibitors.
` The second element of the claim is, basically, the
`combination of the Bifido, in combination with the checkpoint
`to treat cancer. What we found in all three references, as
`we'll go through, are unequivocal statements that that Bifido,
`whether it's in Singh, Kohwi, or Mohania has any cancer
`activity. All the statements are there.
` What Patent Owner has done has said -- tried to get
`around those statements, said, Let's look at the underlying
`data and see if it's trustworthy. But the statements are
`unequivocal. And in our -- in Patent Owner's view, the data
`is strong. And one of the ways we can show the data is strong
`is if we look at other peer-reviewed articles, which expressly
`opine on what the prior art at issue says. And that's what
`we've done here.
` So that's, sort of, the broad overview of our case.
`So if we go to the first one, Korman in View of Singh and
`Dong. So Korman, as it says in Slide 13, it teaches
`systemically administering an immune checkpoint inhibitor,
`such as an anti-PD-1 or a CTLA antibody to treat MC38
`colorectal cancer cells or SA1/N fibrosarcoma cells. And as
`the institution decision stated, there's no question that
`Korman shows, using this checkpoint inhibitors, to treat a few
`different types of cancer.
` If we then go to the secondary reference, Singh,
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`which talks about Bifido. What Singh did was he orally
`administers Bifido, specifically, B. longum in rats, which had
`been subjected to AOM subcutaneously, which had developed
`tumors. And what they found, as stated in Singh, if you now
`look at the middle quote in the abstract, under Exhibit 1004,
`Page 1 abstract, "Data suggests that oral administration of
`probiotic B. longum exerts strong anti-tumor activity."
` Now, there's a lot of criticism from Patent Owner
`about whether the AOM model and the Bifido actually was
`against the carcinogen or whether it was against the tumor
`cell. The evidence shows, first of all, that if we take a
`look at the first quote on the demonstrative, under Exhibit
`1004, Page 2, it says, "It was of interest to evaluate the
`colon tumor inhibitory properties of dietary B. longum in the
`established colon cancer model."
` So it's an established colon cancer model and you
`have expressed statements, as shown in the abstract, that B.
`longum exerts anti-tumor activity. But if we then turn to
`Slide 15, these two -- these references, and there's two more,
`are strong evidence of what a person of ordinary skill in the
`art would have understood Singh to say.
` And if we take a look at Exhibit 1050, Page 5, they,
`in that peer-reviewed paper, say, quote, "Sing et al.
`demonstrated that a dietary administration in rats of
`lyophilized cultures of B. longum resulted in a significant
`suppression of colon tumor incidents and tumor multiplicity."
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` So you have a peer-reviewed article, subsequently
`reviewing Singh, which is also a peer-reviewed article,
`interpreting that reference to say that B. longum showed or
`resulted in a significant suppression of colon tumor incidents
`and tumor multiplicity. Nothing limited to whether it's AMO-
`induced.
` If we then go to the next quote, Zhang, Exhibit
`1051, Page 7505, once again, this ordinary skilled artisan in
`a non -- from a non-biased perspective, not an expert, of
`Patent Owner states, "Dietary administration of
`Bifidobacterium longum had significant suppression of colon
`tumor incidents, tumor multiplicity, and tumor volume."
` So, once again, this is yet another piece of
`evidence showing that one of ordinary skill in the art, when
`interpreting Singh, interpreted it to show anti-cancer
`activity of the B. longum.
` And we have two more articles from Kupathi (ph),
`Exhibit 1051, Page 341, saying, "Singh observed that
`Bifidobacterium longum exerts a strong anti-tumor activity in
`his colon cancer." And we also -- and this is on Slide 16.
`And then on 1052, Page 2, we, once again, have another peer-
`reviewed article, saying, "In rats, Bifidobacterium longum
`administered alone or in associate with non-digestible
`oligosaccharides exhibits strong anti-tumor activity."
` If we then take a look at Slide 17, Singh alleged
`that the mechanism of action could go through a number of
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`different possibilities, but one of which is an
`immunomodulatory role. There's nothing in Singh that
`precludes that immunomodulatory role of the Bifido. In fact,
`if you take a look at what Singh said, they can proceed
`through diverse mechanisms.
` And, indeed, if we then go to Slide Number 19, we,
`once again, have a peer-reviewed article subsequently
`published, opining on the disclosure of Singh. Exhibit 1001,
`Page 6, under the discussion in this article says,
`"Bifidobacterium spp. and LAB are probiotic organisms in
`humans and stimulate immune function and anti-tumor effects."
`Citations to references 19 through 45.
` Singh is 38. So now we have a peer-reviewed
`publication, interpreting Singh, showing the immunomodulatory
`effects. And then when I asked Patent Owner's expert about,
`Isn't it true that that's how a person of ordinary skill in
`the art would construe Singh, to have those immunomodulatory
`effects? And we look at the testimony that's cited on Page 18
`at 1042, 121:4 to 122:12, Patent Owner's expert confirmed,
`yes, that was a correct interpretation of Lee.
` So the other point, if we then now turn to Page --
`Slide 19 -- one second, Judges.
` The question is, what is the immunomodulatory
`properties of B. longum? And Petitioner combined it with
`Dong. Dong described B. longum. And, in fact, what they were
`interested in was what was the activity of a dendritic cell.
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`Because in immunology, basically, you have a dendritic cell,
`which can activate the T-cell.
` And the dendritic cell can spit out a number of
`cytokines; IL-10, IL-12, IL-6, IL-2. And you have to look at
`the ratios. And then if it works on a T-cell and activates
`the T-cell, the T-cell will secrete interferon gamma. Which
`is the hallmark -- the hallmark of an immunostimulatory
`response, known as a Th1 response.
` And this is what Dong found. This is what Dong
`found, that these dendritic cells, upregulated IL-12 and that
`they also, in terms of a T-cell response, the T-cell spit out
`interferon gamma, which is the hallmark of a Th1 response.
` So it's clear that Dong shows an immunostimulatory strain
`of B. longum and that is what is shown on Slide 19, where they
`show that the dendritic cell increased suppression of CD86 IL-
`12, which is an immunostimulatory cytokine and interferon
`gamma. And that in induced maturation of those dendritic
`cells, that would favor a T-cell response of the body in a Th1
`type, the hallmark of an immunostimulatory response in cancer.
`So that's what dong shows for B. longum.
` If we go then to Slide 20, Patent Owner criticizes
`Dong because Dong shows that you also have some upregulation
`of IL-10. However, as Patent Owner has said in other papers,
`it's clearly the ratio of IL-10 to IL-12. And what we know
`here is that because the T-cell spit out the interferon gamma
`and the dendritic cell also upregulated IL-12, that the
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`balanced effect was immunostimulatory.
` And how do we know this? We know this by none other
`than the inventors themselves. If we take a look at Slide 21,
`here are the inventors, Gajewski, Sivan, and Corrales, telling
`you that quote -- Exhibit 2005, Page 1085, "Stimulatory
`interactions between Bifidobacteria and the host immune
`system, including those associated with interferon gamma ,
`have been described previously." So they're talking about an
`immunostimulatory response and they're pointing to interferon
`gamma.
` So they're concluding that Dong shows an
`immunostimulatory Beta Longum. Now, Patent Owner tries to
`exclude this statement, which on its face, is -- it -- for
`Patent Owner to then put in an exhibit and try to exclude it
`tells you something. So there's no merit to the exclusion.
`And furthermore, what they're trying to run away from is the
`expressed acknowledgement by the inventors themselves that
`interferon gamma is the key cytokine in terms of determining
`an immunostimulatory response. And that's what they show
`here.
` And then they also show in the Motion to Exclude
`that, well, possibly, the inventors aren't one of ordinary
`skill. But I would point out, Your Honors, that if we take a
`look at Exhibit 2005, there are no less than 1, 2, 3, 4, 5, 6,
`7, 8, 9, 10, 11, 12 authors on that paper, and it's a peer-
`reviewed paper. So it's clearly persuasive and strong
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`Case PGR2019-00002
`Patent 9,855,302 B2
`evidence that B. longum is immunostimulatory.
` In terms of whether the -- now, once again, Patent
`Owners says, Well, we don't really agree with Dong's
`methodology, and I'd direct you to Slide 22. I don't think,
`at this point, it's time cost (sic) efficient for me to go
`through each of Petitioner's rebuttals to Patent Owner's
`criticisms of Dong. But nevertheless, what is ultimately
`important and what is shown by the inventors is that the
`inventors themselves said it was immunostimulatory.
` So these criticisms, they don't have any water. And
`Dr. Braun does not believe that Petitioner has shown anything
`in terms of whether or not Dong's data is trustworthy.
` JUDGE MITCHELL: Do you argue that the statements of
`the inventors rise to the level of an admission?
` MR. BAUER: I did -- we did not.
` JUDGE MITCHELL: Okay.
` MR. BAUER: We did not. Although, you could.
` JUDGE MITCHELL: Okay.
` MR. BAUER: Nevertheless, it's from the inventors
`themselves. And, indeed, if we take a look at Slide 23, if
`you look at the inventors' own patent, Exhibit 1001, Column
`40, Line 33 to 54, they're also looking at dendritic cells and
`interferon gamma. What they say at Lines 45, "JAX-derived DCs
`elicited elevated levels of T-cell IFN-gamma production." And
`then pointed to that as showing an immunostimulatory response.
` So putting this all together, Korman shows the use
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`Case PGR2019-00002
`Patent 9,855,302 B2
`of CPIs to treat a couple of different types of cancer; colon
`cancer and fibrosarcoma cancer. Singh tells you, I can orally
`administer Bifidobacterium longum and treat colon cancer, and
`I also have a number of different mechanisms, one of which,
`immunomodulatory.
` Then you add Dong in, which tells you B. longum is
`immunostimulatory. When you put that all together, there's
`your case of obviousness. What is the suggestion to combine?
`First of all, if we take a look at Slide 24, under In re
`Kerhoven, "It is prima facie obvious to combine two
`compositions, each of which is taught by the prior art to be
`useful for the same purpose." So here, both Korman and Singh
`tell you, we're going to use each agent to treat a certain
`type of cancer.
` So that's enough for the reason to combine.
`Furthermore --
` JUDGE SNEDDEN: Is it the same type of cancer, colon
`cancer?
` MR. BAUER: Yes.
` JUDGE SNEDDEN: Yeah.
` MR. BAUER: And Dong shows that the Beta longum's
`immunostimulatory. So you -- there have -- now, the
`combination to combine and the reasonable expectation of
`success, based on any cancer activity of Korman, any cancer
`activity of Singh, and also the immunostimulatory effect. So
`that's our position why Korman, in view of Singh and Dong,
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`render the claims obvious.
` Now, with respect to some dependent claims, I think
`we'll rest on the papers in Slide 25, we're talking about an
`antibiotic. We put forth a reference that shows that you can
`use an antibiotic to, basically, deplete the microbiome. And
`then you have the Bifido, so the population of Bifido would be
`greater than, relatively, it was before. And whether it was
`one day before, we just think that's routine optimization.
` So let's turn to Slide 26, which is Korman in View
`of Kohwi. I won't go over Korman because we know it's a CPI
`to treat a number of -- a couple of subsets of cancers. So
`let's Kohwi, which would be Slide 27. Once again, this is a
`secondary reference or the primary reference for Bifido, where
`there's unequivocal statements showing the anti-cancer
`properties of B. infantis or B. adolescentis. And if we take
`a look at the abstract, the statements are unequivocal.
` "The effect of intraregional injections of bacteria
`on subcutaneously transplanted tumor (25 x 10 to the third)
`produced a complete regression in all mice, when treatment
`with B. infantis was started from one day after tumor
`inoculation for six times, where all the control mice were
`dead." All of them. "And the majority of mice rejected the
`re-challenge."
` It also stated in the abstract, "Intraperitoneal
`injection of B. infantis against intraperitoneally
`transplanted tumor also exhibited a remarkable anti-tumor
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`Case PGR2019-00002
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`effect." And we have yet another -- so we have unequivocal
`statements of the anti-tumor effect of Kohwi.
` And once again, if we go to Slide 28, we have peer-
`reviewed publications, which are confirming that Kohwi shows
`anti-cancer of the Bifidobacterium or cited therein. And
`that's specifically Exhibit 1054, Page 485 and Exhibit 1004,
`Page 838. And those quotes are shown on Slide 28.
` And if we then move to Slide 29, once again, we have
`yet another third-party peer-reviewed publications, opining on
`what Kohwi shows. And while the printing may not be perfect,
`it may be a little blurry, what it says is, in the left-hand
`column is, "Bifidobacterium infantis," that's the type. The
`tumor is a Meth A. sarcoma. The animal is a mouse. The -- it
`says, "Target immunomodulation." And then the outcome is,
`"Tumor regression."
` So, once again, it's just another example of another
`party, looking at Kohwi, showing any tumor activity. And then
`if we move to Slide 30, I just want to point out a couple
`things very quickly, Judges. Given these unequivocal
`statements from Kohwi, Patent Owner's left with really
`scraping at the edges. And what they've said is that,
`somehow, the data in Table 3 conflicts with or is not
`statistically significant and is different than the data in
`Table 6.
` But what I'd like to show, Your Honor, if I may --
`can I approach the screen on --
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` JUDGE MITCHELL: Sure.
` MR. BAUER: What I'd like to show is that if you
`take a look at this data here, this one, you have a 50 percent
`survival rate. Now, the assay for this -- these three,
`according to Patent Owner themselves is the same as this.
`They say -- the Patent Owner says this is not statistically
`significant, even though control, they all died and with
`Bifido infantis, 50 percent survived, and 1, which is
`statistically significant here, you now have 47 percent
`survived.
` So clearly, you're showing a 50 percent survival
`rate. And the reason I mentioned the number 50 percent,
`because if you take a look at -- when we get to enablement,
`the response rates, they're telling you 10 percent, 15 percent
`is enough for this Court to believe that the response is
`effect, but yet, in this here -- this chart here, 50 percent
`is not good enough.
` Now, the reason that may not be statistically
`significant on the upper chart, Table 3, is that there just
`may not be enough mice. But they all died. They were 50
`percent and the bottom, which was statistically significant,
`they died. So we think the evidence is unequivocal that, yes,
`the data does who that the Beta infantis and adolescentis of
`Kohwi has anti-tumor effects on Meth A. sarcoma cells and that
`the prior art recognized that.
` And then if we go to Slide 31, we also note that
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`Kohwi suggest that it could have an immunological stimulation,
`that it was augmented or stimulated. And I direct the Court
`to Exhibit 1007, Page 5. And once again, in terms of the
`immunomodulatory component of Kohwi, I direct the Board's
`attention to Slide 32, where Lee subsequently published a
`peer-reviewed article, commented on Kohwi and said, quote,
`"Bifidobacterium spp. And LAB are probiotic organisms in
`humans and stimulate the immune function and anti-tumor
`effects."
` Yet another confirmatory reference showing the anti-
`tumor effects of the Bifidobacterium of Kohwi. So, once
`again, if we then turn to Slide 33, in terms of the
`obviousness case, we've got a primary reference, Korman,
`showing CPIs against colon cancer and fibrosarcoma. We have
`Kohwi showing both B. infantis and B. adolescentis to exert
`any tumor activity against Meth-A sarcoma cancer.
` So, now -- once again, we have two agents, the same
`purpose. We also have the immunostimulatory data in text in
`Kohwi as confirmed by Lee. So, once again, we have the
`reasonable -- we have the motivation to combine and
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