Ex Parte Tardi et al

Patent Trial and Appeal Board

Sep 26, 2016

13122454 (P.T.A.B. Sep. 26, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
13/122,454 05/10/2011
25225 7590 10/13/2016
MORRISON & FOERSTER LLP
12531 HIGH BLUFF DRIVE
SUITE 100
SAN DIEGO, CA 92130-2040
FIRST NAMED INVENTOR
Paul Tardi
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
Address: COMMISSIONER FOR PATENTS
P.O. Box 1450
Alexandria, Virginia 22313-1450
www .uspto.gov
ATTORNEY DOCKET NO. CONFIRMATION NO.
532552003000 9240
EXAMINER
POPA, ILEANA
ART UNIT PAPER NUMBER
1633
NOTIFICATION DATE DELIVERY MODE
10/13/2016 ELECTRONIC
Please find below and/or attached an Office communication concerning this application or proceeding.
The time period for reply, if any, is set in the attached communication.
Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the
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PTOL-90A (Rev. 04/07)
1 RECORD OF ORAL RECORD
2 UNITED STATES PATENT AND TRADEMARK OFFICE
3 -------
4 BEFORE THE PATENT TRIAL AND APPEAL BOARD
5 -------
6 Exparte PAUL TARDI, LAWRENCE MAYER,
7 and DAVID BERMUDES
8
9
10
11
12
Appeal2014-008998
Application 13/122,454
Technology Center 1600
13 Before JOHN NEW (by Videoconference ), RICHARD
14 SMITH and DEVON NEWMAN, Administrative Patent Judges
15 The above-entitled matter was heard on Thursday, September
16 8, 2016 at the U.S. Patent and Trademark Office, 26 South Fourth Street,
17 Courtroom 322, San Jose, California at 9:35 a.m.
18 APPEARANCES:
19 FOR THE APPELLANTS:
20 Morrison & Foerster LLP
21 By: KATE H. MURASHIGE
22 kmurashige@mofo.com
23 12351 High Bluff Drive
24 Suite 100
25 San Diego, California 92130
26 (858) 720-5112
Appeal 2014 008998
Application 13/122,454
1 PROCEEDINGS
2 (9:35 a.m.)
3 THE USHER: Calendar No. 53. Appeal No.
4 2014-008,998. Serial No. 13/122,454. Judges, this is
5 Attorney Kate Murashige from Morrison & Foerster.
6 JUDGE NEWMAN: We have Judge New in our
7 Alexandria office.
8 MS. MURASHIGE: How do you do?
g JUDGE NEW: Good morning.
10 JUDGE SMITH: Judge Newman is to my right
11 and I'm Judge Smith. We are familiar with your case. You
12 have 2 0 minutes. You may be gin when you 're ready.
13 MS. MURASHIGE: Thank you. First I wanted to
14 introduce Phil McGarrigle. I mentioned that he would be
15 here. He's the patent counsel for Jazz Pharmaceuticals.
16 Jazz Pharmaceuticals recently purchased Celator
17 who is the assignee of these patents. So clearly he has an
18 interest in the outcome of this proceeding and he's willing to
19 answer any questions concerning the merger or anything like
20 that to the extent it's relevant, but I wanted to let you know
21 who he was.
22 JUDGE SMITH: Thank you.
23 MS. MURASHIGE: So on the case itself I think
24 it's clear from the proceedings so far that there doesn't seem
25 to be a dispute on the law here. I think the examiner and we
26 agree that, if indeed the results that we have shown are those
Appeal 2014 008998
Application 13/122,454
1 that would not be expected and are surprising, that this
2 would convey patentability because the only outstanding
3 rejections are basically obviousness. So, I mean, we didn't
4 cite any case law for that because there was no disagreement,
5 but we could always do US versus Adams or something like
6 that.
7 In any event --
8 JUDGE NEW: Counsel, I have one question if I
9 can just sort of cut to the root of this at least as far as my
10 thoughts are concerned. And that is reviewing your brief
11 and reviewing the declaration of Dr. Mayer I'm not finding
12 any evidence that a person of ordinary skill in the art at the
13 time the application was filed would not expect liposomes to
14 be able to move out across a normalized blood vessel into a
15 tumor. You've argued that it's surprising, but where is the
16 evidence that it is, in fact, surprising?
17 MS. MURASHIGE: Well, the ability of
18 liposomes to transit into tumors out of the vasculature was
19 known to be a function of the leakiness of the blood vessels
20 in the tumor. This is the enhanced permeation and retention
21 effect or EPR, and that was well established at that time.
22 Dr. Mayer's declaration -- he as an expert in the field
23 testified that this was the understanding of the art, that the --
24 the liposomes relied on the leakiness of the blood vessel to
25 go in and stay in and exert their effects.
Appeal 2014 008998
Application 13/122,454
1 So I don't think the issue is whether they could
2 get across at all in normalized vessels. It's whether they
3 would be inhibited from doing so as compared to the case
4 when there was no normalization of the vasculature.
5 JUDGE NEW: Correct.
6 MS. MURASHIGE: So what they expect --
7 JUDGE NEW: Correct. But my understanding
8 from the prior art in the working file here is that it was
9 recognized that normalized blood vessels are still more leaky
10 than normal blood vessels would be in non-tumor tissue.
11 And consequently why wouldn't you expect liposomes to be
12 able to move out of these more leaky than normal blood
13 vessels in subjects that had been treated with antiangiogenic
14 drugs?
15 MS. MURASHIGE: You would expect them to be
16 less able then to penetrate and be retained than if it were not
17 normalized. It's true, and the Jain paper shows that, that the
18 permeability is intermediate between the leakiness and the
19 unnormalized and the actual normal. But what you would
20 expect is that at least you would have a reduction in the
21 effect of the liposomes because they would be less able to
22 get through and less able to be retained.
23 JUDGE NEW: But what troubles me about that,
24 Counsel, is the lack of evidence on that point. We don't
25 have any idea about the size-to-leakiness ratio between
26 liposomes and normalized tissue. We don't know how big
Appeal 2014 008998
Application 13/122,454
1 the gaps are. We don't know how it filters or what size it
2 filters.
3 In other words, if a normalized blood vessel is
4 acting as a physical filter, we need to know the size of that
5 filter and whether or not it will prevent liposomes moving
6 through and I don't see any evidence of that at all.
7 MS. MURASHIGE: I don't think there's any
8 evidence it prevents liposomes going through. What the
9 understanding in the art was was that the bigger the -- the
10 bigger the gaps and the vasculature, the higher the effect of
11 EPR. And that's the Maeda papers that are well established.
12 It's really interesting. Yesterday I was at a
13 meeting with another client who were interested in getting
14 large molecules into a tumor and they asked me, "Do you
15 know about Maeda's work on the EPR effect?" And it's a
16 well-known effect that the permeation is enhanced by the
17 greater the permeation of the vessel. So if you decrease the
18 permeability, you would expect to decrease the ability of the
19 liposomes to get in.
20 That's not saying they don't get in at all, but what
21 the results show in the application are that the results are not
22 -- are not reduced, which is what you would expect -- I
23 mean, it could still be there, but they are not reduced. They
24 are, in fact, enhanced and that's what you would not expect.
25 JUDGE NEW: Okay.
26 MS. MURASHIGE: If that makes sense to you.
Appeal 2014 008998
Application 13/122,454
1 JUDGE NEW: Thank you. It does. Thank you.
2 Continue, please.
3 MS. MURASHIGE: So I think that really is
4 basically the case that the fact that there's some
5 normalization that is not complete doesn't mean that it isn't
6 going to negatively affect the permeability of the liposomes
7 and the retention of the liposomes.
8 JUDGE SMITH: It sounds like, though, at the
9 end of the day you're just saying that no one really knew
10 whether the addition of the antiangiogenic agent would --
11 MS. MURASHIGE: Well, no one had tried it, I
12 mean, if that's what --
13 JUDGE SMITH: Well, you're saying there was
14 no evidence that you couldn't do that, that it would prevent
15 the uptake of the chemical agent --
16 MS. MURASHIGE: That would -- I'm sorry to
17 interrupt you.
18 JUDGE SMITH: It's okay.
19 MS. MURASHIGE: That would assume that
20 somebody assumed that it would work and therefore tried it.
21 And the art discouraged them from doing so. So there was
22 nobody to collect the evidence. Only the applicant did that
23 and demonstrated that it worked. In fact, it would be -- if
24 there were evidence to the contrary, then we wouldn't have
25 the invention at all because the invention wouldn't work.
Appeal 2014 008998
Application 13/122,454
1 JUDGE SMITH: Yeah. You have -- I mean, you
2 know, one of the things we're obviously looking at is the art
3 that's before us. The Tardi reference actually discusses the
4 combination and it's so --
5 MS. MURASHIGE: Yes.
6 JUDGE SMITH: So, you know, we're -- in the
7 face of that we need --
8 MS. MURASHIGE: Yeah. I understand.
9 JUDGE SMITH: We need some kind of evidence
10 to show us -- to basically overcome the prima facie case and
11 we don't seem to have that.
12 MS. MURASHIGE: Well, I understand the Tardi
13 reference has one paragraph that suggests that, but the Tardi
14 reference is not limited to liposomes. The Tardi reference
15 discusses all kinds of deli very vehicles including Dextrins
16 and things like that. So I don't think that's determinative at
17 all. What I think our evidence of the state of the art is, A,
18 given somebody who's familiar with the art. Granted, he's
19 the inventor, but somebody who's familiar with the art who
20 says not it's his opinion, but that this is what the art
21 understand.
22 B, there are two review articles that he's cited to
23 cite earlier works that say the same thing, that you need the
24 leakiness of the vasculature in order to get this enhanced
25 ac cum ula ti on of lip o some s.
Appeal 2014 008998
Application 13/122,454
1 And the examiner's only evidence of this -- of the
2 normalization enhancing the chemotherapeutic effect is small
3 molecule drugs. That is understood. It's only these large
4 liposome-carried drugs that are inhibited from entering.
5 That is understood. And you're right. Of course,
6 there's no evidence that normalization inhibits that because
7 nobody did it. And we did it, but it was surprising that it
8 worked.
9 Should I -- that's sort of the story on the
10 outstanding obviousness rejection. I think the only other
11 thing I would want to add to that is that the Tong paper
12 that's cited by the examiner only discusses a very small,
13 quote, unquote, "large molecule BSA," which is much
14 smaller than the liposomes. It's an elongated 4 inches -- I
15 mean 4 nanometers by 14 nanometers which I looked up on
16 Google.
17 JUDGE SMITH: Could you address a little bit
18 the obviousness-type double patenting rejection. It seems to
19 me from your briefing that your argument is basically the
20 same.
21 I know they are applying Flowers, and I want to
22 ask you about Flowers here in a minute, but it means to me
23 that your argument as to why there is no double patenting
24 simply devolved into the same argument about this so-called
25 surprising effects or result I should say of combining the
26 chemo agents with the antiangiogenic agents.
Appeal 2014 008998
Application 13/122,454
1 MS. MURASHIGE: It does. I think Flowers was
2 more disturbing to us because they -- you could consider it
3 an accidental anticipation if we didn't give the same
4 liposomes, but the difference there is that Flowers is using
5 their liposomes to carry the agents not as chemotherapeutic
6 agents, but as antiangiogenic agents and as such they would
7 not have to extravasate.
8 I picked a quote out of the Jain paper, you know,
9 saying that the antiangiogenesis effect is being asserted
10 within the blood vessel itself. And I could read the quote if
11 you wanted, but --
12 JUDGE SMITH: Yeah. I was confused because
13 you referenced the abstract of Flowers and it does talk about
14 delivery of the agents. So I was a little confused from your
15 briefing.
16 MS. MURASHIGE: Well, the -- the Jain article
17 says that in order to conduct angiogenesis they sprout new
18 blood vessels for existing ones. So that wouldn't require
19 entry and recruit endothelial cells from the bone marrow. So
20 that would require entry and I don't know, you know, why
21 Flowers would think anything different.
22 JUDGE SMITH: You're saying Flowers' teaching
23 is just incorrect from a technical standpoint?
24 MS. MURASHIGE: Yeah. I think those things
25 are known.
Appeal 2014 008998
Application 13/122,454
1 So I guess the only thing I would add is that I
2 think the examples in the specification pretty clearly show
3 that not only is the chemotherapeutic effect which is shown
4 by the lack of growth of the tumor not decrease, but it's
5 actually enhanced, which no one would have predicted.
6 JUDGE SMITH: Well, that seems to be
7 suggested, though, by some of the references that the
8 examiner provided.
g MS. MURASHIGE: Sorry?
10 JUDGE SMITH: That seems to be suggested by
11 some of the references that the examiner provided.
12 MS. MURASHIGE: Well, only the -- the only
13 reference that she provided that is to the contrary is the
14 Terstriep one that was part of her rejection which is confined
15 to small molecules and the Tong document that is not related
16 to molecules as large as what we're looking at. And the
17 other documents on Kerbel, that was interesting. I didn't
18 realize until I prepared for this that the quote out of Kerbel
19 was attributed to Jain 2005, and I looked all through the Jain
20 article in 2005 and it's not there. So I don't know why it's
21 there.
22 The review by Eshun that Dr. Mayer cited states
23 that it's documented that small molecule drugs linked to or
24 encapsulated and liposomes show preferential accumulation
25 in tumors due to leaky angiogenic vessels with intracellular
26 paths as large as 600-800 nanometers and impaired lymphatic
Appeal 2014 008998
Application 13/122,454
1 drainage. And that quote -- and that's in the review -- comes
2 from a 2004 article. So that precedes the priority date. So I
3 think those are the only documents she has.
4 JUDGE SMITH: Do you have anything else you'd
5 like to ask?
6 MS. MURASHIGE: Okay. Thank you very
7 much.
8 JUDGE SMITH: No. I was going to ask if they
9 have anything else and then I was going to ask you.
10 MS. MURASHIGE: Oh, I'm sorry.
11 JUDGE NEWMAN: Judge New?
12 JUDGE NEW: Not at this time. Thank you.
13 JUDGE SMITH: Judge Newman?
14 JUDGE NEWMAN: No. Thank you.
15 JUDGE SMITH: Thank you very much. We'll
16 take the case under advisement.
17 MS. MURASHIGE: Okay. Thank you.
18 (Whereupon, the hearing concluded at 9: 52 a. m.)
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