`Entered: August 18, 2014
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`Trials@uspto.gov
`571-272-7822
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` 1 RECORD OF ORAL HEARING
` 2 UNITED STATES PATENT AND TRADEMARK OFFICE
` 3 - - - - - -
` 4 BEFORE THE PATENT TRIAL AND APPEAL BOARD
` 5 - - - - - -
` 7 ARIOSA DIAGNOSTICS
` 8 Petitioner
`
` 9 v.
`
` 10 VERINATA HEALTH, INC.
` 11 Patent Owner
` 12 - - - - - -
` 13 IPR2013-00276 and IPR2013-00277
` 14 Patent 8,318,430
` 15 Application No. 13/368,035
` 16 Technology Center 1600
` 17 - - - - - -
` 18 Oral Hearing Held: July 16, 2014
` 19
` 20 Before LORA M. GREEN, TONI R. SCHEINER, and RAMA G. ELLURU,
` 21 Administrative Patent Judges.
`
` 22 The above-entitled matter came on for hearing on
` 23 Wednesday, July 16, 2014 at the U.S. Patent and Trademark
` 24 Office, 600 Dulany Street, Alexandria, Virginia at 2:00 p.m.,
` 25 in Courtroom A.
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`IPR2013-00276 and IPR2013-00277
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` 1 APPEARANCES:
` 2 ON BEHALF OF THE PETITIONER:
` 3 GREG H. GARDELLA, ESQ.
` 4 KEVIN B. LAURENCE, ESQ.
` 5 DIANNA DeVORE, Ph.D., ESQ.
` 6 Oblon, Spivak, McClelland, Maier
` 7 & Neustadt, L.L.P.
` 8 1940 Duke Street
` 9 Alexandria, Virginia 22314
` 10 703-413-3000
` 11 ggardella@oblon.com
` 12
` 13 ON BEHALF OF THE PATENT OWNER:
` 14 MICHAEL T. ROSATO, ESQ.
` 15 STEVE PARMALEE, ESQ.
` 16 ALLISON M. De WISPELAERE, Ph.D., ESQ.
` 17 Wilson Sonsini Goodrich & Rosati
` 18 701 Fifth Avenue, Suite 5100
` 19 Seattle, Washington 98104
` 20 206-883-2529
` 21
` 22
` 23
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` 25
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`IPR2013-00276 and IPR2013-00277
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` 1 P R O C E E D I N G S
` 2 (2:00 p.m.)
` 3 JUDGE GREEN: Good afternoon. Please be seated.
` 4 Welcome everyone. This is the final oral hearing
` 5 for cases IPR-2013-00276 and IPR-2013-00277. The Board
` 6 instituted inter partes review in these proceedings on
` 7 October 25th, 2013. Both proceedings involve patent
` 8 8,318,430.
` 9 At this time we would like counsel to introduce
` 10 yourselves and your colleagues, beginning with Petitioner.
` 11 MR. GARDELLA: Good afternoon, Your Honor, Greg
` 12 Gardella from Oblon Spivak on behalf of Petitioner. I am
` 13 joined by Dianna DeVore of Ariosa Diagnostics, Kevin
` 14 Laurence, also of Oblon Spivak, and Sally Brashears of
` 15 Convergent Law Group.
` 16 JUDGE GREEN: Okay. Thank you. Patent Owner?
` 17 MR. ROSATO: Thank you, Your Honor, Michael Rosato
` 18 for the Patent Owner. I have my colleague Steve Parmalee and
` 19 Allison de Wispelaere.
` 20 JUDGE GREEN: Thank you.
` 21 Welcome to the Board.
` 22 Consistent with our previous order, each party has
` 23 one hour to present their arguments. Petitioner will proceed
` 24 first to present its case as to the challenged claims and may
` 25 reserve rebuttal time for its case. Thereafter, Patent Owner
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` 1 will respond to Petitioner's case.
` 2 Counsel for Petitioner, do you have a copy of your
` 3 demonstratives for the court reporter, opposing counsel, and
` 4 the panel?
` 5 MR. GARDELLA: We do, Your Honor.
` 6 JUDGE GREEN: If you would provide that. Then
` 7 would you like to reserve rebuttal time?
` 8 MR. GARDELLA: Please, Your Honor, 40 minutes,
` 9 please.
` 10 JUDGE GREEN: 40 minutes?
` 11 MR. GARDELLA: Yes.
` 12 JUDGE GREEN: Thank you. And you may proceed when
` 13 you are ready.
` 14 MR. GARDELLA: Thank you, Your Honor.
` 15 So to kick off the discussion, I would like to
` 16 first discuss for a bit the technologies which would be known
` 17 to a person skilled in the art, so a distinction is useful to
` 18 recognize between the molecular biology on the one hand and
` 19 working with the actual molecules, running the actual tests,
` 20 designing the actual tests, on the one hand, and the
` 21 bioinformatics piece, which is on the tail end. And that is
` 22 largely number crunching.
` 23 So the bioinformatics piece is not really
` 24 implicated by the combination, not in any principal respect.
` 25 The combination principally implicates the molecular biology,
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` 1 how you design the tests, what tests would work together, how
` 2 one could modify a test.
` 3 So as we see in the background of the invention,
` 4 it is described that the need which gave rise to the putative
` 5 invention is a need for an approach or a method which
` 6 selectively enriches nucleotides by massively parallel
` 7 sequencing to the end of detecting aneuploids.
` 8 And, again, and as we will see, it is the
` 9 molecular biology piece which is really central to the
` 10 combinations. And this translates in this field to wet lab
` 11 experience.
` 12 Now I would like to introduce the experts.
` 13 Professor Morton from Harvard University.
` 14 JUDGE ELLURU: Counsel, could you please refer to
` 15 the -- identify the slide number that you are referring to?
` 16 MR. GARDELLA: Certainly. My -- my copy of the
` 17 slides are not numbered. This should be number 3. Is that
` 18 correct?
` 19 MR. LAURENCE: It is Exhibit 1048.
` 20 MR. GARDELLA: You are referring to the
` 21 demonstrative slide number?
` 22 JUDGE ELLURU: Yes.
` 23 MR. GARDELLA: This should be slide number 3.
` 24 Could I get a copy of ours as numbered, so I can make that's
` 25 right? Good.
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` 1 So we're on slide 3.
` 2 So Professor Morton has published extensively in
` 3 prenatal genetic testing. And importantly Professor Morton
` 4 has run biochemical -- excuse me, a molecular biology or wet
` 5 lab that actually performs the test, actually uses the
` 6 equipment.
` 7 Professor Nussbaum is to the same effect. He
` 8 likewise has supervised a wet lab. And he is the chief of
` 9 genomic medicine at the University of California, San
` 10 Francisco.
` 11 So both of these professors have published
` 12 extensively, again, in the field of prenatal genetic testing.
` 13 And they have familiarity with the molecular biology aspects
` 14 of the test, which as we will see that's primarily what's
` 15 implicated by the issues that have arisen in this case.
` 16 So now in contrast Associate Professor Butte, a
` 17 relatively young fellow in comparison to our experts, he,
` 18 with respect, seems to be quite competent in the field of
` 19 bioinformatics. That's what he has done. When it comes to
` 20 actually the wet lab side, handling the molecules, designing
` 21 the tests, running the tests, he has not actually supervised
` 22 such a biochem or wet lab.
` 23 Cynthia Morton, our Harvard expert, is familiar
` 24 with Dr. Butte from earlier work. She was familiar that he
` 25 did not have familiarity with the wet lab aspects of the
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` 1 technology. And Dr. Butte during his deposition acknowledged
` 2 as much. So this will help explain to some degree the
` 3 positions that we see in which two experts with due respect
` 4 were head scratchers.
` 5 So further to the point of this distinction
` 6 between bioinformatics knowledge, on the one hand, versus
` 7 knowledge of the actual sequencing techniques, on the other,
` 8 Dr. Butte was presented during his deposition a four-page
` 9 brochure. This is Exhibit 1010.
` 10 This is an important document in this case because
` 11 it is relied upon by, for instance, Professor Nussbaum at
` 12 paragraph 21 of his declaration as showing that, you know, as
` 13 to the motivation to combine and the knowledge that this
` 14 would be readily doable, the proposed combination, that is,
` 15 and that it would be advantageous, he could have just used
` 16 off-the-shelf systems to do this.
` 17 So now in response to questioning on this exhibit,
` 18 which is drafted to the customer, which would be someone in a
` 19 wet lab, say a first year post-doc in a wet lab, Dr. Butte --
` 20 and we, of course, have to take him at his word -- indicated
` 21 he couldn't even begin to guess how long it would take to
` 22 interpret this document fully.
` 23 And the second quote is to the same effect. So,
` 24 you know, perhaps this is why the positions that we're about
` 25 to see, there is such a difference of opinion between our
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` 1 experts, again, just couldn't make sense of some of the
` 2 allegations Dr. Butte was making.
` 3 Let's cover now the claimed subject matter. One
` 4 useful way to conceptualize the claims here is to think of
` 5 them in terms of, well, on the firsthand, you have to detect
` 6 aneuploidy by sequencing 100, at least, non-random alleles.
` 7 And then what else does the claim require? Well,
` 8 it essentially requires counting them, so massively parallel
` 9 sequencing does that and indexing. And as we will see in the
` 10 prior art as skilled artisans knew, as Professor Nussbaum
` 11 did, that this was off-the-shelf technology at the time.
` 12 So how does that map to the references in
` 13 question?
` 14 And this is -- what I am about to cover now is
` 15 going to be an important theme that will come up several
` 16 times during today's presentation. Dhallan was 2003. So
` 17 back in that time frame there were only first and second
` 18 generation sequencing technologies available. But even then
` 19 Dhallan proposed to Dr. Butte's count 21 different techniques
` 20 by which you could detect non-random alleles.
` 21 Shoemaker discusses the off-the-shelf, you know,
` 22 then, so Shoemaker is 2007. Illumina's genome analyzer was
` 23 available then, so it discusses the use of that. So
` 24 Shoemaker stands amongst other things for the proposition
` 25 that there is off-the-shelf MPS technologies that one could
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` 1 use.
` 2 And now on the last element here, the indexing,
` 3 Shoemaker was '07. It talks about Illumina, which was again
` 4 at the time the benchmark system.
` 5 Shoemaker is one year before the Illumina kit,
` 6 essentially expansion of the genome analyzer platform, which
` 7 is manifest in this Exhibit 1010. This came out in 2008.
` 8 December 2008 is the date shown, I believe, on this last
` 9 page.
` 10 So Binladen is not here simply because Binladen
` 11 chose to make his own tags. So that's a perfectly acceptable
` 12 way to do it as well. And we will discuss why one skilled in
` 13 the art would have had no difficulty making this combination
` 14 with, you know, custom tags.
` 15 JUDGE ELLURU: Counsel, can you point me to where
` 16 in the petition you discuss the reason to combine these
` 17 references?
` 18 MR. GARDELLA: I believe I can, Your Honor.
` 19 Now, would it be acceptable if I pointed to
` 20 declarations to which we cite?
` 21 JUDGE ELLURU: That's acceptable. I would also
` 22 like to see where you cite those declarations in the
` 23 petition.
` 24 MR. GARDELLA: So could I get a copy of the
` 25 petition from co-counsel? In order to give her a moment to
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` 1 grab that, could I come back to your question?
` 2 JUDGE ELLURU: That's fine.
` 3 MR. GARDELLA: So to make sure we -- could you
` 4 just tee those up for me? And I will direct Your Honor to --
` 5 well, so pull up paragraph 21 of Nussbaum and paragraph 38 of
` 6 Morton's. Actually I guess paragraph 21 of Nussbaum and the
` 7 petition would suffice. So when you have those ready, I will
` 8 answer Judge Elluru's question.
` 9 So while those materials are being prepared, we
` 10 will move on, unless the Board has any other questions they
` 11 would like us to field.
` 12 So Patent Owner had three primary contentions in
` 13 its response. And I emphasize "had" because on inspection of
` 14 their demonstratives, it does appear as though the second
` 15 two, which were the most significant head scratchers to our
` 16 experts, it appears that opposing counsel is going to
` 17 distance themselves substantially from them. These are
` 18 scarcely mentioned in the slides. But, again, so to the
` 19 extent there is kind of a new focus in today's argumentation
` 20 from opposing counsel, I will deal with that on rebuttal.
` 21 With regard to issue number 1, that was made
` 22 before. And that's still an argument. We will address that
` 23 first.
` 24 So with regard to the locater elements, most
` 25 fundamentally any first year post-doc in a wet lab would
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` 1 understand that locator elements or tags are -- I mean that's
` 2 what they are, the nucleotide tags that are used to identify
` 3 a source of a sample.
` 4 And in that regard the different sources can be
` 5 different cells. They can be cells taken at different times.
` 6 Both of those are discussed in Shoemaker. And they can also
` 7 be, you know, consistent with the teaching of Dhallan, which
` 8 says take blood samples from multiple different pregnant
` 9 women naturally. If a first year post-doc even would
` 10 understand that, well, the sample tags in that circumstance
` 11 would naturally be used to track to individuals as opposed to
` 12 cells taken from the same individual, perhaps at a different
` 13 time, as in Shoemaker.
` 14 And just as significantly, if one considers the
` 15 embodiment in Shoemaker in which there is one cell in a
` 16 particular assay -- excuse me, one cell in a well, and that
` 17 embodiment is described in Shoemaker as illustrated and
` 18 conceded by Professor Butte during his deposition. And
` 19 that's the quote we have here on the screen.
` 20 In that embodiment, you have one cell per well, so
` 21 necessarily each cell is going to track to an individual.
` 22 You don't have an agglomeration of cells.
` 23 So that embodiment is probably sufficient to
` 24 address the issue. Let me ask co-counsel, are we ready to
` 25 respond to Judge Elluru's question?
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` 1 MS. DeVORE: I have a first cite for Judge Elluru.
` 2 MR. GARDELLA: So do you have a copy of the
` 3 petition for me?
` 4 MS. DeVORE: I do have a copy of the petition.
` 5 MR. GARDELLA: Could you put that up? Once that
` 6 is queued, I will turn to that.
` 7 Okay. So actually I will address their three
` 8 arguments and then for cohesiveness of the presentation, I
` 9 will return to Your Honor's question.
` 10 So the second issue raised in the response, the
` 11 second primary argument is that in the combined method, you
` 12 would physically combine the fluoro label of Dhallan. You
` 13 would use that specific embodiment and in doing so you would
` 14 cleave off the tag. Our experts' response to that was
` 15 essentially no one would do that.
` 16 As a matter of fact, I was sitting next to
` 17 Professor Morton when she said it in essentially that tone in
` 18 the deposition. This is something that just no one who knows
` 19 this field who has actually worked with the equipment would
` 20 ever do.
` 21 Further to that, Professor Morton explains that in
` 22 Dhallan there is essentially two buckets of techniques. Some
` 23 require fluorescent or radiographic labeling; and others do
` 24 not. I will ask the Board to turn its attention to paragraph
` 25 18 of Morton's declaration.
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` 1 And therein we have a description that as of 2002
` 2 and 2003, many techniques require this sort of labeling, but,
` 3 however, many other techniques do not. And I won't bore Your
` 4 Honors with it, but she lists a couple. This fragmentation,
` 5 fragmentation of DNA in extension to incorporate labels is
` 6 one. A technique that does not require the use of
` 7 restriction enzymes or fluorescent labels. Another is in
` 8 vitro transcription of the loci followed by RNA, cleavage and
` 9 detection, inspection. And there are three others listed by
` 10 Professor Morton in her declaration.
` 11 So, so as to this --
` 12 JUDGE ELLURU: Counsel, when you get to the
` 13 question about the identification of the petition of where
` 14 the reason to combine is located, could you also point me to
` 15 where you talk about, if you do and where it is, where you
` 16 talk about the Dhallan embodiments that do not require the
` 17 use of a restriction enzyme?
` 18 MR. GARDELLA: You know, as to that, Your Honor,
` 19 again, this was a head scratcher. This is not something we
` 20 expected. And so this is something we addressed in the
` 21 second round in the reply.
` 22 So our experts thought with respect that it is not
` 23 something they needed to explain, that one wouldn't use the
` 24 restriction enzyme embodiment, but rather you would use a
` 25 different embodiment.
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` 1 So even more fundamentally this discussion of
` 2 Dhallan is anchored back in 2003. If one steps forward to
` 3 2008, and this is what Professor Nussbaum did in paragraph 21
` 4 of his original declaration, he said, well, in 2008 one of
` 5 the reasons why this would be so obvious is I would know that
` 6 I could implement this whole thing, the whole combined method
` 7 with off-the-shelf equipment and techniques. And he refers,
` 8 of course, to Exhibit 1010 amongst other information.
` 9 But relying on that, he says, well, it is known at
` 10 that point in time that it is all off-the-shelf. Again, that
` 11 is more than a year prior to the filing date.
` 12 Lastly, and then hopefully we will get to Your
` 13 Honor's question, the third argument that they raise -- and,
` 14 again, this is one that I expect you are going to see
` 15 opposing counsel is going to distance himself from now -- is
` 16 that the Binladen sample tags, you know, those are not useful
` 17 because Binladen talks about mitochondrial DNA, as opposed to
` 18 cell-free DNA.
` 19 This likewise our experts also thought was really
` 20 a head scratcher. Here again, any first year post-doc, at
` 21 least if they are in a wet lab, if they have the relevant
` 22 experience, would know that in this respect DNA is just DNA.
` 23 Once you have it isolated, it amplifies the exact same way.
` 24 So a sequence is just a sequence.
` 25 So this, I don't expect you are going to hear much
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` 1 about during opposing counsel's argument. And I see my
` 2 co-counsel is still working a bit. Are you ready?
` 3 (Discussion off the record.)
` 4 MR. GARDELLA: So in response to your question,
` 5 Your Honor, before we get to essentially the final point of
` 6 our case-in-chief, and I realize I might go a couple minutes
` 7 over the 20 minutes. Is that okay? I assume you will take
` 8 it out --
` 9 JUDGE GREEN: It is your rebuttal time. Use it
` 10 however you want to.
` 11 MR. GARDELLA: It is zero sum game, right. I am
` 12 going to direct Your Honor in response to Judge Elluru's
` 13 question, page 17 of the petition, a scientist in the field
` 14 would have had strong incentive to combine these techniques
` 15 because doing so would clearly result in enhanced
` 16 productivity and increased throughput of sample analysis.
` 17 Nussbaum paragraph 36.
` 18 And so now I am going to turn to the Nussbaum
` 19 declaration, paragraph 36. And so in paragraph 36 this,
` 20 importantly, this comes after his discussion of what one
` 21 skilled in the art would know from paragraphs 13 through 25.
` 22 He goes through various just contextual information that
` 23 anybody skilled in the art would know.
` 24 And in paragraph 21 in this lead-up section, he
` 25 talks about how in 2008 this was widespread, that he would be
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` 1 well able to -- to use off-the-shelf techniques such as those
` 2 shown in Exhibit 1010 to implement the technique.
` 3 Now, in paragraph 36, and that's the pin cite,
` 4 which is provided in the declaration. And I am going to move
` 5 you actually to paragraph 109, which is cited on page -- what
` 6 of the petition?
` 7 MS. DeVORE: 41.
` 8 MR. GARDELLA: -- on page 41. And this is the
` 9 correspondence of the combination of Shoemaker and Dhallan
` 10 and Binladen. We have a cite directly to Nussbaum at 109 to
` 11 111.
` 12 And here Professor Nussbaum says, "I have reviewed
` 13 Shoemaker and Dhallan and Binladen. It is my view that the
` 14 combination discloses each element and that one skilled in
` 15 the art would have been motivated to combine these teachings
` 16 as the combination would clearly result in enhanced
` 17 productivity and increased throughput of sample analysis."
` 18 Further to that same point, Professor Nussbaum
` 19 says this at 23, and this is, this is in that background
` 20 section leading up to this. He says what's on the screen.
` 21 "So as a molecular geneticist in 2008, I would have the
` 22 ability to order a commercially available kit for production
` 23 of enriched and indexed libraries, which I could have
` 24 analyzed on a commercially-available massively parallel
` 25 sequencing platform sold by the same vendor."
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` 1 I expect that opposing counsel is going to, you
` 2 know, complain, if you will, about our "reliance" on
` 3 Exhibit 110, so let's just address that. We did in the
` 4 petition precisely what I believe should have been done. We
` 5 relied upon the more detailed patent documents as the primary
` 6 references.
` 7 The relatively short product brochure and other
` 8 information, which demonstrates what was off-the-shelf
` 9 technology at the time, this was presented as the level of
` 10 skill in the art. And our expert properly looked at that
` 11 level of ordinary skill in the art and what would have been
` 12 known by a person skilled in the art to determine that the
` 13 combination would, in fact, have been advisable.
` 14 So I would like to, as my last point, at least for
` 15 my case-in-chief, to take you to page 2 of Exhibit 110. And
` 16 this is, again, what Professor Nussbaum cited.
` 17 And this is by Illumina. This is -- and, by the
` 18 way, Illumina is the Patent Owner. Illumina purchased
` 19 Verinata. Illumina also was at the time the industry
` 20 standard. So this is not some small outfit whose marketing
` 21 literature, you know, has perhaps a -- carries with it some
` 22 puffery. This is Illumina itself.
` 23 Here in the box we see at right, so this comes
` 24 from the first page of the Exhibit 110, fast,
` 25 high-throughput; faster. Second bullet point, cost-effective
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` 1 method; cheaper. Next bullet point, high-quality data;
` 2 better. And next bullet point, simplified analysis. Faster,
` 3 cheaper, better, simpler.
` 4 Off-the-shelf as of 2008. That was the proper
` 5 analysis. That was the proper use of Exhibit 110. The
` 6 arguments that have come back, again, to our way of thinking,
` 7 and with due respect, are head scratchers. So that's how we
` 8 got to kind of a focus on what was just known to, again, to
` 9 our way of thinking, to any first year post-doc. That's the
` 10 reason why we're talking so much about this.
` 11 But the case was presented properly. And we
` 12 submit that there are no defects whatsoever in terms of the
` 13 manner in which it was presented.
` 14 Anything else, co-counsel?
` 15 Judge E