Trials@uspto.gov
`571-272-7822
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`
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`Paper 39
`Entered: July 23, 2020
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`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`MODERNA THERAPEUTICS, INC.,
`Petitioner,
`
`v.
`
`ARBUTUS BIOPHARMA CORPORATION,
`Patent Owner.
`____________
`
`IPR2019-00554
`Patent 8,058,069 B2
`____________
`
`Record of Oral Hearing
`Held: April 22, 2020
`____________
`
`Before TINA E. HULSE, CHRISTOPHER G. PAULRAJ, and
`TIMOTHY G. MAJORS, Administrative Patent Judges.
`
`
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`

`

`IPR2019-00554
`Patent 8,058,069 B2
`
`
`APPEARANCES:
`
`ON BEHALF OF THE PETITIONER:
`
`MICHAEL FLEMING, ESQUIRE
`
`
`C. MACLAIN WELLS, ESQUIRE
`
`
`Irell & Manella, LLP
`
`
`1800 Avenue of the Stars, Suite 900
`
`
`Los Angeles, CA 90067-4276
`
`
`
`
`
`ON BEHALF OF THE PATENT OWNER:
`
`
`
`
`
`
`
`
`
`
`
`The above-entitled matter came on for hearing on Wednesday, April
`
`22, 2020, commencing at 1:00 p.m., by video/by telephone.
`
`
`
`
`
`
`
`
`
`MICHAEL T. ROSATO, ESQUIRE
`STEVEN W. PARMELEE, ESQUIRE
`SONJA R. GERRARD, ESQUIRE
`LORA M. GREEN, ESQUIRE
`Wilson Sonsini Goodrich & Rosati
`701 Fifth Avenue, Suite 5100
`Seattle, WA 98104-7036
`
`
`
`
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`IPR2019-00554
`Patent 8,058,069 B2
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`
`P R O C E E D I N G S
`- - - - -
`JUDGE PAULRAJ: Good afternoon, counsel. This is the final oral
`
`hearing in IPR2019-00554. I'm Judge Paulraj and with me on the video we
`have judges Hulse and Majors. As noted in our trial hearing order, in light
`of the current situation with COVID-19 we'll be conducting this hearing
`entirely by video conference. So, we do have a court reporter present who
`will be transcribing this hearing, although the court reporter will not be seen
`on video. I also understand that members of the public may be listening on
`this hearing. I'm not aware of any confidential information that might be
`discussed but wanted to make sure counsel was aware of that. With that,
`let's start with appearances. Petitioner's counsel first and then Patent
`Owner's counsel.
`
`MR. WELLS: This is Maclain Wells of Irell & Manella on behalf of
`Moderna, Petitioner. Also, on the line dialed in is Michael Fleming also of
`Irell and Manella. And from our client Moderna, Debra Milasincic, head of
`intellectual property.
`
`JUDGE PAULRAJ: Thank you, Mr. Wells. And counsel for Patent
`Owner.
`
`MR. ROSATO: Good afternoon, Your Honor, this is Mike Rosato on
`behalf of Patent Owner. And dialed in should be my colleague Lora Green.
`And it is possible that in house counsel for the Patent Owner Meagan Young
`is dialed in as well. And further in the conference room I have at a distant
`location Franklin Chu and Sonja Gerrard.
`
`JUDGE PAULRAJ: Thank you, Mr. Rosato. So, per the terms of our
`oral hearing order, each side will have 45 minutes to present their arguments
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`IPR2019-00554
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`and each side may reserve some of that time to respond to the other side's
`arguments. I'll ask you how much time you want to reserve when it's time to
`present.
` We are in receipt of the demonstratives that were emailed to the board
`so we have that in front of us as well as full access to the record in this
`proceeding. I want to remind counsel to make sure you do clearly identify
`the slide number that you're referring to as you make your presentation so
`we can follow along. Please also make sure to mute yourself if you're not
`speaking so we avoid unnecessary background noises.
`
`I'm not aware of any outstanding objections to the demonstratives that
`we need to resolve. But I did get a reminder from the court reporter before
`we started that to the extent that there's complicated terminology please
`articulate those clearly and if we need to have them spelled out, we may
`have you do that as well just so we have a clear record. Unless there's any
`other preliminary matters we need to discuss, we can proceed with
`Petitioner's arguments.
`
`MR. WELLS: Yes, Your Honor. Maclain Wells for Petitioner
`Moderna and I would like to reserve 20 minutes of our time for rebuttal.
`
`JUDGE PAULRAJ: That's fine, Mr. Wells, let me go ahead and put
`that on the clock here. So, that would give you 25 minutes for your initial
`arguments. Whenever you're ready.
`
`MR. WELLS: Thank you, Your Honor. So, I would like to begin
`today talking about obviousness, Kendal reference obviousness in view of
`Patent Owner's own 189 prior art publication. Which disclosed the same
`lipid carrier systems that are described in the challenged claims of the 069
`patent.
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`IPR2019-00554
`Patent 8,058,069 B2
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` And so, if we could turn to Petitioner slide 20. This is the cover page
`in the summary of invention from the 189 patent and we're talking here
`about nucleic acid-lipid particles and three different types of lipid
`components. A cationic lipid, a non-cationic lipid and a conjugated lipid.
`And Your Honor's may be aware from the discussions in the papers that the
`non-cationic lipid can be further subdivided into different types of non-
`cationic lipids a phospholipid and a cholesterol.
`
`So, if we proceed to slide 21, in the 189 patent there's this disclosure.
`The lipid nucleic acid particles of the present invention, and it provides
`ranges. And so, we have for the cationic lipid, a 2 to 60 range. This is the
`mol or percentage. For the non-cationic lipid, which would include
`potentially the phospholipid and cholesterol we have 5 to 90. For the
`conjugated lipid, we have .5 to 20 and then it specifically called out 2 as one
`example. And for the cholesterol, when it's present, we have 20 to 55 mol
`percent. And if you go to paragraph 0159 of the 189 patent, it discusses the
`types of non-cationic lipids and gives the examples of a phospholipid, a
`cholesterol or a mixture of a phospholipid and a cholesterol.
` And so, here we have each of the 4-lipid components described in the
`069 patent claims and ranges for each of those 4-lipid components all in the
`same lipid nucleic acid particle. Laid out in one part of the specification,
`these are all intended to be combined together and these four components,
`the cationic lipid, the phospholipid, the cholesterol and the conjugated lipid
`are intended to equal 100 percent of the lipid component in the particle. You
`could, in theory, have additional components but when we're talking about a
`four component system, these should total 100 percent. So, if you increase
`one of them, you have to correspondingly increase another one.
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`IPR2019-00554
`Patent 8,058,069 B2
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`The Petitioner's position is that the board was right in its institution
`
`decision when it addressed these ranges -- the institution decision at pages
`22 through 23. That there is a range disclosed for each of the components.
`Now Patent Owner has alleged that there is no phospholipid range expressly
`disclosed. But we know from 0159, the paragraph, that the phospholipid is a
`type of non-cationic lipids specifically listed. And the non-cationic lipid
`could also include cholesterol, so a mixture of those too.
`
`So, there are embodiments disclosed that have the four components.
`Every embodiment in the patent doesn't have the four components but that's
`not a requirement for obviousness. The requirement is there is a disclosure
`of an embodiment with the four claimed lipid components.
`
`And Patent Owner's own expert admitted that the 5 to 90 non-cationic
`lipid range would apply to phospholipids during his deposition. At exhibit
`1025 page 167 10 through 22, he answered, this is a range that is of
`composition. 5 mol percent to 90 mol percent and any number of different
`phospholipids that are recited here.
`
`So, the prior art discloses a phospholipid range as it's illustrated in
`0152 and 0159. And all of the experts admit that there is a phospholipid
`range disclosed. Now the phospholipid range, if it's a three particle system
`is 5 to 90 percent. But when you have cholesterol as well as a phospholipid
`you have to take into account that the cholesterol is going to decrease that
`range. So, if you have 20 to 55 percent cholesterol, you would have to
`adjust the range of 5 to 90.
`
`So, for example, if we know we have a minimum amount of 20
`percent cholesterol, then we decrease the amount of non-cationic lipid range
`available for the phospholipid to 0 to 70 percent. And this is --
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`IPR2019-00554
`Patent 8,058,069 B2
`
`JUDGE PAULRAJ: Mr. Wells, if I could interrupt here.
`
`MR. WELLS: Yes.
`
`JUDGE PAULRAJ: So, I think the big question for us is why we
`
`should consider this argument persuasive in light of how the board decided
`on the similar arguments and found unpersuasive in the 739 IPR. Could you
`go straight to that issue as to, you know, whether there's a reason why the
`record in this case might compel a different result.
`
`MR. WELLS: Yes, there's several reasons, Your Honor. And as
`Your Honor and the board noted in the institution decision, the claims of the
`735 patent are distinct from the claims of the 069 patent. Specifically,
`they're broader. For example, the cationic lipid range there goes all the way
`up to 85 percent. So, we have a significant difference in the overlap
`between the disclosures in the prior art for the cationic lipid. The 2:60
`versus a 50 to 65 percent compared to in the 739 IPR, a cationic lipid range
`of 50 to 85 percent.
`
`In addition, in the final decision in the 739 IPR, the Patent Board did
`not address the phospholipid disclosures of the 189 patent and whether or
`not there was one and did not address specific ranges. There was one page
`in that decision addressing the prior disclosures of the Patent Owner. And
`that simply announced that based upon the arguments that were put forward
`in that IPR, a showing hadn't been made that these different components
`would be combined together in a way addressed by those patent claims.
`
`Before the board here, there is different arguments put forward in both
`the petition and in response to Patent Owner response. So, there's different
`arguments that this board can consider. And for that reason, the board can
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`IPR2019-00554
`Patent 8,058,069 B2
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`reach a different decision without contradicting the 739 -- the findings of the
`739 patent board.
`
`JUDGE PAULRAJ: Okay thank you. You may proceed.
`
`MR. WELLS: So, given the disclosure of overlapping ranges for each
`of the lipid components as put forth in paragraphs 0152 and explained in
`0159, under Peterson, this gives rise to a prima facie case of obviousness.
`Meaning that Petitioner's burden of production has been met by this and now
`the burden of production is on the Patent Owner to come forth with some
`evidence as to why obviousness should not be found.
`
`Patent Owner makes arguments in its papers that even if an
`overlapping range is present, a motivation to combine and likelihood of
`success still need to be shown. But the case law of Peterson and Dupont
`established that the likelihood of success and motivation are derived from
`the overlap itself and hence, that's why a prima facie case exists.
`
`JUDGE PAULRAJ: Does Dupont or any other cases that you've cited
`for the overlapping ranges, a presumption that those cases talk about. Do
`they address the situation where, you know, you might have to imply or infer
`a particular range? You know, I'm talking about the phospholipid range,
`obviously, where, you know, I think more or less you'd have to admit unless
`you're going to go to the specific examples and we can discuss those, you
`know, separately. At least the ranges that are disclosed more generally in
`the 189, the 196 and the 554 don't explicitly talk about a range of
`phospholipids. So, can you explain why we should consider the Dupont line
`of cases under these circumstances.
`
`MR. WELLS: Yes, Your Honor. So, in an obviousness analysis, one
`of the first steps is determining the scope of the prior art. And in
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`IPR2019-00554
`Patent 8,058,069 B2
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`determining the scope of the prior art, the standard is a person of skill in the
`art would understand the disclosures to be based upon the disclosures
`therein. If the standard is not, oh, you have to have an expressed disclosure
`where it says the phospholipid range is X is what a POSITA would
`understand. And that's the IXL IP case. And while that wasn't an
`overlapping range case, it provides the standards that a person of skill in the
`art would understand from the disclosures.
`
`There's no case law that we are aware of that says that an overlapping
`range must be expressed. It's based upon the understanding of a person of
`skill in the art looking at the disclosures in the prior art reference. And we
`would suggest that looking at paragraphs 0152 and 0159, this is not complex
`gymnastics to come up -- legal, intellectual gymnastics to come up with the
`phospholipid range. This is simple subtraction. You have 5 to 90 for the
`non-cationic lipid and it's made up of a two species, a cholesterol and a
`phospholipid and that's disclosed in 0159. So, the cholesterol is eating up
`some of that 5 to 90 range and you adjust it accordingly.
`
`JUDGE PAULRAJ: Yeah, but couldn't you come up with the
`phospholipid range? Let's start with the -- I think your arguments, first of
`all, assume that you must necessarily include a phospholipid range based on
`say paragraph 152 of the 189 patent. I don't see any disclosure that
`phospholipid must necessarily be part of this component. I understand that
`189 elsewhere discloses phospholipid among the possible neutrolipids. Let
`me break that question down to two parts. So, why should we read
`paragraph 152 that the ranges that you're talking about has necessarily
`including an additional non-lipid or I'm sorry, non-cationic lipid component
`beyond the cholesterol?
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`MR. WELLS: So, Your Honors, the cholesterol that's listed here is in
`
`addition to the non-cationic lipid. It says, the nucleic acid may further
`comprise a cholesterol. So, that's in addition to the cationic lipid, the non-
`cationic lipid and the conjugate. Now, the cationic lipid doesn't have to be a
`phospholipid according to paragraph 0152 and we don’t allege to the
`contrary. The phospholipid is one species that is disclosed. So, there are
`embodiments disclosed that include a phospholipid, a cholesterol, a cationic
`lipid and a conjugated lipid.
`
`There is no requirement in the law that every embodiment disclosed in
`the patent has to render obvious to claims. The question is whether an
`embodiment that does render the obvious to claims would have been
`evidence to a person of skill in the art given these disclosures. And our
`contention is absolutely based upon not only this but as Your Honor is
`aware, there is testing, actual reduction to practice in the 189 patent and
`there are two systems that are disclosed. What we call a 2:30 system and the
`2:30 refers to the conjugated lipid amounts and the cationic lipid amount and
`a 2:40 system.
`
`And in both of those systems, so absolutely every example that was
`reduced to practice in the 189 patent includes a cationic lipid, a
`phospholipid, a cholesterol and a conjugated lipid. Given those disclosures,
`it would be readily apparent to a person of skill in the art that there are
`embodiments, including those four lipid components disclosed in the 189
`patent. Did that answer your question?
`
`JUDGE PAULRAJ: It does but it raises another concern. I think this
`is the heart of perhaps the arguments on reply and the motion to strike, right.
`You know, so it does seem like you're shifting your arguments a little bit
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`IPR2019-00554
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`from the ranges that are disclosed. Perhaps, in paragraph 152 and the other
`range disclosures in the prior art to the specific embodiments and the 2:40
`embodiment, for example. Where in the petition did you specifically rely
`upon the 2:40 embodiment that I think is coming into play at this point?
`
`MR. WELLS: Sure, Your Honor. So, the 2:40 embodiment is
`described in the petition for the disclosures of the 189 patent. At various
`spots it's discussed extensively. But, for example, the -- I'm getting down to
`it. One second, Your Honor, I apologize.
`
`JUDGE PAULRAJ: Sure.
`
`MR. WELLS: For example, at paragraph 31 when we're discussing
`the claim one in light of the PCP, the 196 PCP or the 189 publication.
`
`JUDGE PAULRAJ: Sorry, you referred to paragraph 31. I don't
`necessarily have paragraph numbers for this.
`
`MR. WELLS: I apologize, page 31 of the petition.
`
`JUDGE PAULRAJ: Okay.
`
`MR. WELLS: And there's reference made to the 2:40 formulation as
`being the reason why the 189 publication is also being included as a
`reference. So, as you will recall, the 196 publication or 196 PCP and the
`189 publication have substantially similar disclosures. The main difference
`between the two references is that the 189 has this additional 2:40 test.
` And this 2:40 testing was discussed by Dr. Janoff in his initial
`declaration attached to the petition at paragraphs 96 and paragraphs 109.
`Where he laid out this 2:40 testing, how it related to the testing in the 069
`patent and in paragraphs 109, used it as part of his analysis for invalidity.
`So, to say that this is a new issue, I don’t think is entirely accurate.
`Obviously, we are responding to arguments that Patent Owner raised in its
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`IPR2019-00554
`Patent 8,058,069 B2
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`Patent Owner response as well which is an alternative basis for this to be a
`proper reply.
`
`JUDGE PAULRAJ: All right, well let me focus on the petition first
`and your arguments in the petition relying upon the 2:40. So, I see the
`paragraph you're referring to on page 31 of the petition. And all I read from
`that, at least with respect to 2:40, is that there's a difference between 189 and
`the 196. The primary difference is that it discloses additional testing related
`to the 2:40.
` I don't think there's any, you know, to be fair, and I'm not sure how I
`would read that as suggesting that the 2:40 formulation, the disclosure there
`additionally provides a separate reason. Is there anything -- let me go
`straight to perhaps the disclosure about the phospholipids which, I think, is a
`more relevant issue here. So, when we get to the phospholipid ranges, pages
`38 to 39 of the petition, is there anything in that part of the petition that
`discusses the 2:40 disclosure?
`
`MR. WELLS: So, Your Honor, the answer is the specific pages don't
`reference the 2:40 to my knowledge at that specific section. But if you go
`back to page 26 of the petition, in the discussion of the 189 publication and
`what its disclosures encompass, it not only details the ranges at page 25
`where it says, a publication discloses SNALP's comprised in overlapping
`ranges.
` But the very next sentence says, in addition, the 189 discloses testing
`relating to the 2:40 formulation that Patent Owner identified as prior art
`formulations. And then it details what the contents are and says -- and
`details that there was in vivo testing demonstrating that these were
`efficacious. And says, these additional disclosures confirm formulations
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`with high cationic lipid percentages, for example, 40 percent and low lipid
`percentages, for example, 2 percent.
`
`So, the 189 ranges have always been informed by the examples in the
`189 specification. And it would be legal error to actually ignore those in
`addressing the content of the prior art. Now do they separately call this out
`in each individual discussion of the 189 publication in the petition, no. But
`certainly, the disclosures of the 189 publication were made clear to include
`this 2:40 formulation as further clarification.
`
`JUDGE PAULRAJ: And just to be clear, part of the new argument
`that you made, when I say new arguments, I'm not using that in pejorative
`term. But compared to the prior case, the 739 IPR, your reliance on the 2:40
`is something that's relatively new compared to the 739 IPR, is that right?
`
`MR. WELLS: There's been a different discussion of that. Now the
`739 IPR is under appeal. We actually have appeal briefs going in very soon
`on that. And so, the 2:40 was raised in that petition. It wasn't discussed to
`the extent that the issue has come up in this petition. So, I think that there
`are different arguments relating to that in this hearing as opposed to the prior
`hearings. Does that answer your question, Your Honor?
`
`JUDGE PAULRAJ: It does, thank you Mr. Wells. Just to follow up
`on the appeal of the 739. So, do you have any sense of when oral argument
`in that appeal might be heard or when the fed circuit might issue a decision
`in that case?
`
`MR. WELLS: Opening briefs are due on March 4th or May 4th,
`sorry. So, we're a ways away from any movement on that. Briefing has just
`started.
`
`JUDGE PAULRAJ: Okay, thank you.
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`MR. WELLS: Now, we've already discussed how Peterson
`
`establishes given these overlapping ranges of prima facie case of
`obviousness. And we've also discussed how even if that prima facie case
`didn't apply, the 2:40 formulation and the working examples in the 189
`patent would still give rise to an understanding of obviousness based upon
`routine optimization.
`
`And so, what I would like to do is if we could go to slide 22. And so,
`here we have the 2:40 formulation. The working example identified in the
`petition and identified in the 189 patent and this is the closest prior art to the
`1:57 that's been identified in these proceedings. And so, we have the 4-lipid
`components payload and we have them being effective in vivo.
`
`If you proceed to slide 24, side by side we have the 2:40 formulation
`and the 1:57 formulation laid out. And you can see, it's not just that the lipid
`-- different lipids are present. It's that the specific species are actually being
`used in the prior art. So, we have the same payload, we have the same
`cationic lipid, the same conjugated lipid, the same cholesterol and
`phospholipids that are very closely aligned. And Patent Owner's own expert
`admitted that he wouldn't expect DPPC and DSPC to behave any differently
`in this context.
`
`And so, all we're doing at this point is saying we're using this defined
`system and we're tweaking the numbers slightly in order to come up with a
`range that works the best. And so, if you go to slide 26, you can see we have
`a disclosed range of 2:60. So, we're just upping the cationic lipid slightly
`and you have to accommodate that by decreasing something else. So, in this
`sense it's decreasing the cholesterol slightly. This is the definition of routine
`optimization given these overlapping ranges. And, in fact, --
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`JUDGE PAULRAJ: I mean, I think that brings up the question, right,
`
`so why do you -- why are you choosing to first increase the cationic lipid
`percentage to beyond what is in the 2:40 formulation. And even if you
`would do that, why are you choosing to decrease the cholesterol to within
`the claim ranges as opposed to perhaps any of the other components.
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`MR. WELLS: Sure, Your Honor, and I'm happy to address that. Just
`to be clear though, what you're talking about is a motivation to do a specific
`optimization and that is not required under Peterson. That's assumed, given
`the overlapping ranges. But the reason of Peterson is found not apply and
`now we're discussing it out of the context of that prima facie case.
` The reason for increase in the cationic lipid is put forth in the petition
`and cationic lipid is included in the particles. It negates the charge on the
`payload, the nucleic acid payload. And it was known that you needed to
`have enough to negate that charge. And that if you increase the amount of
`cationic lipid, you could potentially increase transection efficiency and
`where is that shown?
`
`Well, if we go to slide 29, for example, this is the 910 publication that
`is put forth in -- that is discussed in the file history of the patent. And this
`illustrates that it was known that higher mol percent of cationic lipids can be
`better. So, we see here where they're putting forth testing and they're doing
`this type of routine optimization. They're saying let's test cationic lipid at
`15, 20, 25, 30, 35, 40 and see what works the best and it got better as it got
`higher.
`
`And, in fact, Patent Owner, if you go to slide 30, we see a trend in
`Patent Owner's disclosures. The earlier disclosures from 2003 have low
`cationic lipid, 15 mol percent. But as these ionizable cationic lipids became
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`more prevalent, we knew we didn't have to have the toxicity concern, we
`could include more. And so, we see that going up to 30 percent, up to 40
`percent and, in fact, these are just the actual ones tested. And, in fact, the
`range for this is up to 60 percent.
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`So, you have the ability to include these additional higher amounts of
`cationic lipid without the toxicity concerns given the fact that you're
`developing these ionizable cationic lipids. And, in fact, Patent Owner's own
`expert admitted that he was unaware of any toxicity concerns with
`DLnDMA which is the cationic lipid used in testing of both the 189
`publication and the 069 patent.
`
`JUDGE PAULRAJ: All right, thank you, Mr. Wells.
`
`MR. WELLS: Does that answer your question?
`
`JUDGE PAULRAJ: It does and you've run out of the allocated time
`for your initial arguments. Would you like to reserve the rest for your
`rebuttal?
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`MR. WELLS: If I could cover a couple of topics quickly, Your
`Honor. I think they're important and I just want to make sure that we touch
`on them.
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`JUDGE PAULRAJ: Okay.
`
`MR. WELLS: If you look at the 069 patent testing, I'm looking at
`slide 27. This illustrates the type of routine optimization that we're talking
`about here. We have a defined system and we have different amounts of
`lipids being tested to find out what works the best. Slide 28 is a post patent -
`- post priority date reference that Patent Owner submitted. What this
`illustrates is exactly the same type of routine optimization. This was
`common in the field.
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` Now in response to our showing, if there's an overlapping range under
`a prima facie case of obviousness under Peterson, then Patent Owner has to
`come forward with evidence as to why obviousness doesn't apply. Or if you
`look at this additional evidence and find that Peterson doesn't apply but there
`still is obviousness based upon the additional evidence and the working
`examples then Patent Owner has to come forward with evidence why it
`doesn't apply. And so, Patent Owner's primary response is unexpected
`results.
` And so, if we can go quickly to slide 47, this is Patent Owner's -- what
`Patent Owner relies upon is the 1:57 formulation testing in the 069 patent.
`Your error bars here and I can't tell whether there's any difference between
`how group 11 which is the 1:57 formulation and group 12 which is a 2:40
`type formulation perform. They appear to perform with error bars the same.
`And Patent Owner's own expert admits that they're very close at the least.
`That's not an unexpected result when compared to the prior art.
`
`In addition, Patent Owner points to a commercial embodiment of --
`for the patent Potiseran. Potiseran's target formulation is outside of the
`scope of the claims. So, there's no nexus between this alleged commercial
`embodiment. And so, if you go to slide 55, the takeaway is that the claim
`scope is broad. It covers any payload, any lipid component and any
`formulation within the range. We're talking about hundreds of different
`cationic lipids that were available. DNA payloads, RNA -- siRNA payloads
`are dramatically different in their size. And the testing was very limited.
`Only a few components, only one formulation to 1:57 and only with siRNA
`payloads.
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`Very briefly, Your Honors, the dependent claims Patent Owner only
`
`disputes claims 8, 14 through 18 and 20 through 22. Most of the dependent
`claims have slightly narrower ranges but they always will overlap with the
`disclosures in the 189 and hence the same analysis applies. Claims 16 and
`17 relates to encapsulation as is shown in the 189 testing the patents are
`efficacious in vivo indicating that they have a resistance to degradation in
`serum.
` And regarding claims 18, there's an overlapping range for the nucleic
`acid lipid ration in the 189 patent and claim 22 simply calls for a standard
`carrier, a salient solution when you're applying this. And that's
`acknowledged to be a standard practice at paragraph 0242 of the 189 patent.
`So, with that, unless there's additional questions, I will turn it over.
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`JUDGE PAULRAJ: Thank you, Mr. Wells. I'll give you 17 minutes
`for your rebuttal. Mr. Rosato, whenever you're ready.
`
`MR. ROSATO: Thank you, Your Honor. I'm ready and for time, I
`think I get to reserve some time. If so, I'd like to reserve 10 minutes.
`
`JUDGE PAULRAJ: Okay, thank you. So, that will give you 35
`minutes and, of course, if you need to go over, I'll extend the same courtesy
`and take that time off your sur-rebuttal as needed. Whenever you're ready.
`
`MR. ROSATO: Thank you, I appreciate that. Okay so, I mean, I
`tried to address this in what I believe is an organized manner but I'm, of
`course, happy to address any issues as pending any questions from the panel.
`But I'd like to start with the obviousness case as set forth in the petition.
`Then we'll move on to the arguments that developed in the reply.
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`But starting with the obviousness case as set forth in the petition
`materials, I'll reference slide 11 here. Each of the three obviousness
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`challenges were fairly straightforward in their nature. Each of the three
`grounds relied on this theory that the prior art disclosed lipid ranges that
`overlap with the lipid ranges that were recited in the claim. And the
`petitioner cited to the cases of Peterson and Dupont claiming that is a legal
`matter, the identification of overlapping ranges in the art rendered the
`challenged claims obvious. Now we'll talk a fair bit about this case law and
`we'll return to the phospholipid range. But I want to start with the
`motivation rationale here.
`
`And, you know, beyond citing this legal theory, when we look for
`analysis in the petition, what we find is the analysis is quite thin. The
`petition materials, the e