trials@uspto.gov
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`571-272-7822
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`IPR2015-00990, Paper No. 67
`IPR2015-01093, Paper No. 65
`August 23, 2016
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`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
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`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
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`COALITION FOR AFFORDABLE DRUGS II, LLC,
`Petitioner,
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`v.
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`NPS PHARMACEUTICALS, INC.,
`Patent Owner.
`____________
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`Cases IPR2015-00990 and IPR2015-01093
`Patent 7,056,886 B2
`____________
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`Held: June 23, 2016
`____________
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`
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`BEFORE: LORA M. GREEN, JACQUELINE WRIGHT
`BONILLA, and SHERIDAN K. SNEDDEN, Administrative
`Patent Judges.
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`
`
`The above-entitled matter came on for hearing on Thursday, June
`23, 2016, commencing at 9:30 a.m., at the U.S. Patent and
`Trademark Office, 600 Dulany Street, Alexandria, Virginia.
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`571-272-7822
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`IPR2015-00990, Paper No. 67
`IPR2015-01093, Paper No. 65
`August 23, 2016
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
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`COALITION FOR AFFORDABLE DRUGS II, LLC,
`Petitioner,
`
`v.
`
`NPS PHARMACEUTICALS, INC.,
`Patent Owner.
`____________
`
`Cases IPR2015-00990 and IPR2015-01093
`Patent 7,056,886 B2
`____________
`
`Held: June 23, 2016
`____________
`
`
`
`BEFORE: LORA M. GREEN, JACQUELINE WRIGHT
`BONILLA, and SHERIDAN K. SNEDDEN, Administrative
`Patent Judges.
`
`
`
`The above-entitled matter came on for hearing on Thursday, June
`23, 2016, commencing at 9:30 a.m., at the U.S. Patent and
`Trademark Office, 600 Dulany Street, Alexandria, Virginia.
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`MATTHEW L. FEDOWITZ, ESQUIRE
`JEFFREY D. BLAKE, ESQUIRE
`MARY R. BRAM, ESQUIRE
`ALIREZA BEHROOZ, ESQUIRE
`Merchant & Gould
`1900 Duke Street, Suite 600
`Alexandria, Virginia 22314
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`Cases IPR2015-00990 and IPR2015-01093
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`APPEARANCES:
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`ON BEHALF OF THE PETITIONER:
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`ON BEHALF OF PATENT OWNER:
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`JOSEPH R. ROBINSON, ESQUIRE
`ROBERT SCHAFFER, ESQUIRE
`DUSTIN B. WEEKS, ESQUIRE
`HEATHER ETTINGER, ESQUIRE
`Troutman Sanders
`875 Third Avenue
`New York, New York 10022
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`P R O C E E D I N G S
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`JUDGE SNEDDEN: Good morning. This is the final
`hearing for IPR2015-00990 and consolidated with
`IPR2015-01093. I'm Judge Snedden. I have with me Judges
`Bonilla and Green. Who do we have here today for petitioner?
`MR. FEDOWITZ: On behalf of petitioner, I'm
`Matthew Fedowitz. This is my partner, Jeff Blake, Mary Bram
`and Alireza Behrooz.
`JUDGE SNEDDEN: Welcome. Nice to meet you.
`And for patent owner?
`MR. ROBINSON: Joseph Robinson. I'm here with
`Dustin Weeks, Robert Schaffer and Heather Ettinger. We believe
`that Margo Furman is in the air somewhere trying to get here
`today from NPS and Shire.
`JUDGE SNEDDEN: Thank you. Just briefly, I'll go
`over our procedure today. Each party will have 60 minutes of
`total time to present its arguments. Petitioner will open the
`hearing by presenting its case regarding the challenged claims for
`which we instituted trial. Patent owner will then respond to
`petitioner's arguments.
`Petitioner, you may reserve time to respond to patent
`owner's presentation. So with that, I'll let you begin. Would you
`like to reserve any time?
`MR. FEDOWITZ: I would like to reserve 15 minutes.
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`JUDGE SNEDDEN: I'll start the clock when you
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`begin.
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`MR. FEDOWITZ: In addition, since the cord is a little
`short, my colleague is going to sit here to operate the slides.
`Also, I'll be discussing the technical arguments, and my
`colleague, Jeff Blake, will be discussing commercial success and
`long-felt need.
`Your Honors, we have demonstratives. May I approach
`and give them to you?
`JUDGE SNEDDEN: Yes.
`MR. FEDOWITZ: Your Honor, before I get started, I
`want to briefly preview the items I'm going to discuss today.
`They include what the prior art discloses and how it can be
`rationally applied to the claims at issue. I'm going to discuss
`patent owner's alleged unexpected results. I'm going to address
`patent owner's arguments regarding the alleged complexities and
`the new argument that you will hear today about proteins and
`peptides being different. And I'm also going to discuss the
`contradiction in Dr. Carpenter's publications.
`The standard review of review in this inter partes
`review requires a showing that the facts and the prior art
`demonstrate the instituted claims are obvious by a preponderance
`of the evidence. Petitioner, through its petitions and exhibits in
`the 990 and 1093 IPRs, have met this requirement. We've
`demonstrated that each of the limitations of the claims at issue are
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`in the prior art. This is set forth in the claim charts, in the
`petitions and the declarations we have submitted. Based on these
`disclosures and its institution decision, the Board concluded that
`there was a reasonable likelihood that the claims at issue are
`unpatentable.
`In response to this, patent owner alleged that the
`instituted claims were novel despite all the limitations being
`found in the prior art. However, patent owner's grand scheme
`attempts to argue that the complexity of the formulations at issue
`and that one of ordinary skill in the art would never arrive at the
`limitations claimed despite their being suggested in the prior art.
`This grand scheme, however, is fraught with
`contradictions of what was well known in the prior art. It also
`directly contradicts the prior art statements made in the
`publications by Dr. Carpenter, patent owner's declarant. He
`discloses in those publications a rational approach to formulation
`design. Indeed, one of the most pronounced contradictions is the
`very fact that the complications alleged by patent owner are not
`even considered in the specification of the '886 patent. In fact,
`one of the new arguments you'll hear today is that what was
`known about formulating proteins and peptides cannot be applied
`to each other. This is a completely new argument by patent
`owner.
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`JUDGE BONILLA: What do you mean by new
`argument?
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`MR. FEDOWITZ: We haven't heard this before.
`JUDGE BONILLA: They are raising it for the first
`time today?
`MR. FEDOWITZ: This is the first time we've heard it.
`We saw it in their demonstratives. In fact, in patent owner's
`response, they cite protein/peptide and use them interchangeably
`more than 80 times. For them to change course now represents
`yet another contradiction for the record.
`Nevertheless, I want to make it completely clear that the
`'886 patent describes GLP-2 as a protein. At column 1, line 42 --
`the pointer doesn't work so well on this screen, but if you look at
`line 42 on the right-hand side, it says GLP-2 is a protein.
`The '886 patent also describes GLP-2 as a peptide at
`column 1, lines 5 through 6. That's right there at the top. Let me
`repeat that. The '886 patent says GLP-2 is a protein and it's also a
`peptide. This is important today, important because you are
`going to hear this new argument about proteins and peptides
`being different. The reality is, though, the '886 patent should
`have never issued, as the claims at issue represent only the
`predictable use of prior art elements according to their established
`functions.
`Formulation science is a very mature science, and that is
`what the '886 patent is directed to. Patent owner will argue today
`that this is all serendipity. However, that's not the case. The
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`maturity of the formulation field allows one to apply well-known
`principles across a range of pharmaceuticals and products.
`JUDGE BONILLA: Can you identify for me real
`quick, where exactly does the patent say it's a protein?
`MR. FEDOWITZ: On the right-hand side about
`midway down.
`JUDGE BONILLA: I'm sorry, I can't see. What line is
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`it?
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`MR. FEDOWITZ: Line 42.
`JUDGE BONILLA: I see it, thank you.
`MR. FEDOWITZ: And this is in demonstrative slide
`number 3, just to be clear for the record. As I mentioned, this is a
`formulation patent. For example, on the face of the patent, the
`'886 patent clearly identifies it as a formulation patent. The title
`states that this relates to GLP-2 formulations. The abstract on the
`lower right-hand side there says or describes the invention as
`being directed to formulations of GLP-2 peptides.
`Slide 3, if we look at the field of the invention in lines 5
`through 8, it specifically states, and I quote, The present invention
`provides formulations for GLP-2 peptides and analogs thereof
`and that the invention provides formulations of GLP-2 peptides
`and GLP-2 analogs.
`Also, in the background of the invention just below that
`on the left-hand column and carrying over to the right-hand side,
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`it identifies a need for a stable peptide formulation. It's that spot
`on the bottom right-hand corner.
`If you could turn to slide 4, in fact, the FDA's electronic
`Orange Book, which we've reproduced here, even identifies the
`'886 patent as claiming a drug product. You can see that in the
`box just above the second box up where it says Drug Product
`Claim. And the '886 patent is the second patent listed there.
`JUDGE SNEDDEN: Was this need for a stable
`formulation identified in the prior art?
`MR. FEDOWITZ: Yeah, we have that. If you would
`like, I can go to our claim charts and find that. We have that and
`I can point that out in a moment.
`The Drucker '379 patent also disclosed here, however,
`it's directed to a drug substance. You can see that in the column
`just to the left of the drug product claim column. Therefore,
`given that the claims at issue relate to a formulation and
`formulation science is very mature and a very crowded field, it is
`not at all remarkable that the claims at issue are found in the prior
`art.
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`Patent owners questioned petitioner's declarant's
`credentials. However, Dr. Palmieri is an expert in the
`formulation design and has spent a career in the field not only in
`academia but in the industry. Dr. Palmieri's background,
`education, service on advisory boards regarding excipients are set
`forth in our papers. To be clear, Dr. Palmieri is clearly in
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`possession of a tool box, a formulator's tool box from which he
`can operate and design formulations, and he's clearly able to
`opine on this subject matter of the claims at issue.
`As I mentioned earlier, all of the limitations of the
`claims are found in the prior art. I'm not planning to go through
`limitation by limitation. If you would like, I could, but these are
`all -- all the limitations and all the citations to the prior art are set
`forth in our claim charts, our petitions and our declarations.
`JUDGE GREEN: I don't think the question is whether
`everything is found in the prior art. I think the question is would
`you have had a reason to combine everything in the way the
`claim does and have a reasonable expectation of success. So I
`think that's probably what we should focus on.
`MR. FEDOWITZ: Absolutely. And that analysis starts
`with the Drucker '379 patent. The Drucker '379 patent is a
`starting point for a roadmap that leads to each of the publications
`we've identified. For example, Drucker '379 discloses GLP-2 and
`its analogs. It also discloses therapeutically effective amounts of
`GLP-2 and its analogs, and it also specifically discloses HgLI2,
`GLP-2. If you could turn to slide 13 -- and this is all set forth in
`slide 5, the specific analogs and disclosure of Drucker '379.
`In addition, Drucker '379 describes formulations for
`injection, buffer to a physiologically tolerable pH. It discloses
`phosphate buffer saline as a suitable buffer. It suggests that
`GLP-2 formulations may be lyophilized, and that's a key here,
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`because that's what leads in to the disclosure in Kornfelt. And
`before I leave Drucker '379, it discloses that the glucagon gene
`yields peptide products that are related such as glucagon and
`GLP-2.
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`It's this very disclosure of lyophilized formulations that
`provides the link for one of ordinary skill in the art to recognize
`the application of Kornfelt. Kornfelt discloses the use of an
`analog of the claimed peptides with certain excipients. Slide 11,
`for example, Kornfelt discloses a stabilized pharmaceutical
`composition containing glucagon and a stabilizing amount of
`histidine. It also discloses including the concentration of
`histidine claimed in the '886 patent.
`JUDGE SNEDDEN: This argument seems to suggest,
`though, that wherever you have a lyophilization formulation, it is
`necessary to add the components that Kornfelt had. Couldn't you
`just have a lyophilized formulation without mannitol, sucrose or
`histidine?
`MR. FEDOWITZ: You could. However, the disclosure
`in Drucker discloses the lyophilization. Kornfelt discloses how
`you could stabilize that protein through the use of histidine. And
`then what's really key here is the disclosure in Osterberg which is
`really a guide book for the use of histidine and protein
`stabilization. They are all linked intimately together.
`Lyophilization of the GLP-2 and its analogs in Drucker, Kornfelt
`discloses a similar protein peptide, also the use of histidine and
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`lyophilization. And then you have a really detailed disclosure in
`Osterberg of how to carry out the stabilization using histidine.
`In fact, if you could turn to slide 15, Osterberg shows
`that certain amino acids may act as a stabilizer and a buffer and
`highlights histidine as a multifunctional protein stabilizer. It also
`discloses that sugars and amino acids protect the protein by
`preferential exclusion during freezing and by glass formation by
`functioning as a water substitute in a dried state. It also discloses
`that the addition of sucrose abolishes the crystallization of
`L-histidine. That can be found on Exhibit 1030 at page 304. And
`this is very important to formulation design. Osterberg further
`shows that freeze-drying of L-histidine from solutions having a
`pH in the range of 4 to 8 show that L-histidine has a rather low
`tendency to crystallize during freeze-drying.
`And what's very ironic is the fact that even though
`Dr. Carpenter chooses to criticize Osterberg, Osterberg cites
`Dr. Carpenter. If you look in the top left-hand quote there, you'll
`see in parentheses Carpenter and Crowe. That's our
`Dr. Carpenter from this case. In fact, it's not the first time he's
`cited. He's cited a second time in that same quotation under
`Arakawa. Arakawa is the first author, but if you look in the back
`of this reference, you'll see that Dr. Carpenter is listed as a third
`author of that article.
`JUDGE SNEDDEN: I notice that Osterberg, the data
`presented there is focused mainly on sucrose. Are we to make
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`any distinction between sucrose and mannitol there? Are there
`principles here that apply equally to mannitol?
`MR. FEDOWITZ: I think that the disclosure talks
`about how sucrose can reduce the crystallization of histidine and
`the interplay of the two. I would have to double check on
`mannitol. But we see Osterberg as a real guide book here, how to
`use histidine, how its interplay works with sucrose and how it can
`be applied.
`There is clearly a motivation to combine these prior art
`references. If you could turn to slide 19, there was a need for a
`stable peptide formulation. Dr. Carpenter even discusses the need
`for stable peptide formulations in Exhibit 1049, page 199 and
`Exhibit 1050 at page 969. There is no teaching away from
`petitioner's combinations. There is no rebuttal to petitioner's
`position and there are no citations provided that rebut petitioner's
`positions. Dr. Carpenter argues that secondary structure is not
`important. However, in his 1996 and '97 articles, he consistently
`stresses the importance of maintaining secondary structure in
`lyophilized protein formulations.
`There is no support for histidine being problematic and
`unpredictable either. The only article cited by patent owner in
`this regard are dated after 1999. These would not be considered
`in the obviousness analysis. In addition, known protocols and
`finite options provide a reasonable expectation of success here.
`If you could turn to slide 20 --
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`JUDGE GREEN: Just a bookkeeping question, when
`you are referring to the exhibit numbers, you are referring to them
`in the 1093? I know the exhibit numbers don't match up.
`MR. FEDOWITZ: You are right. I think they are the
`0990. Yeah, it's the first one.
`JUDGE GREEN: I'm looking at the 990 now and
`Exhibit 1050 in there is -- oh, it is the deposition. Sorry about
`that.
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`MR. BLAKE: Excuse me, Your Honor, I believe for
`ours the exhibit numbers are the same in both.
`JUDGE GREEN: I think there are some places where --
`MR. BLAKE: I think that might be for the patent
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`owner.
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`MR. FEDOWITZ: Some of them are -- they line up
`eventually, but you are right, at the beginning there's some
`awkwardness with the exhibit numbers. I'll apologize for that.
`We'll get it cleared up.
`As I mentioned, there is no support for histidine being
`problematic or unpredictable. The only article cited by patent
`owners in this regard are dated after 1999, and these would not be
`considered in the obviousness analysis.
`JUDGE BONILLA: Can you give us the exhibit
`number on that, the ones that they cite that's post 1999?
`MR. FEDOWITZ: We'll get that. It's Exhibit 2052.
`2052 for sure. We'll check on the others. If you go to slide 19 --
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`actually, slide 20, I think it's also important to note with
`Carpenter 1996, that article emphasizes that it's necessary to only
`satisfy four criteria to provide a lyophilized protein peptide
`formulation with long-term stability. And in fact, it's mentioned
`twice in that article. And we've highlighted it here, both in the
`left-hand column and the right-hand column.
`If you go to slide 16, Dr. Carpenter even recognizes that
`Cleland, et al., provides a system for formulating therapeutic
`proteins and peptides. This system here addresses aggregation,
`deamidation and oxidation.
`Slide 19, Carpenter '96 and '97 also provide guidance on
`choosing excipients for lyophilized formulations. Carpenter calls
`out histidine, mannitol and sucrose as particularly useful. This is
`in Exhibit 1041, paragraph 70.
`Kornfelt discloses a finite number of preferable
`combinations. In addition, there are no unexpected results despite
`patent owner saying otherwise. Patent owner has alleged that
`examples 2 through 4 in Figures 2 through 6 demonstrate
`unexpected results in an attempt to counterbalance the weight of
`the prior art, rendering the claims obvious in an effort to salvage
`these claims.
`These examples and figures, however, provide no
`unexpected data. For example, regarding Figure 2, there is
`nothing unexpected here. I'll jump back to this in a moment. If
`you could go to slide 12, instead, patent owner's position fails to
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`take into account the broad range of pH from 1 to 7 disclosed in
`Kornfelt. This is at the very top, third line down on the
`right-hand side there. You'll see it says an interval of 1 to 7. In
`fact, claim 8 of Kornfelt states that pH is adjusted to an interval
`of 2 to 7. This disclosure makes it completely clear that histidine
`can be used across a broad range of pHs.
`What's more, Figure 2 is never intended to be
`characterized as unexpected results. The terms surprising,
`unexpected or any synonym of those words cannot be found in
`the file history or specification of the '886 patent. Rather, it is
`only an example demonstrating the effect of various amino acids
`additives on the stability of GLP-2. In fact, Figure 2 shows that
`the histidine data is supposedly better than histidine and
`phosphate combination highlighted by patent owners.
`Ironically, however, example 2 does not describe a
`formulation of histidine that is found in the first bar in Figure 2 in
`the patent. The combination of histidine and phosphate cannot be
`expected -- unexpected if histidine is better. In fact, there's
`nothing special about histidine when compared to other amino
`acids in Figure 1. Figure 2 also represents nothing more than the
`predictable use of known components having known functions
`before the priority date of the '886 patent. Histidine was known
`as a buffer and stabilizer prior to December 30, 1999.
`Slide 13, Drucker '379 discloses buffering to a
`physiologic pH with a phosphate-buffered saline. Also in U.S.
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`patent number 5,656,730, this is Exhibit 1089, it discloses using
`histidine with a phosphate buffer and a physiologic pH for
`preparing frozen storage stable proteins. And that's found at
`column 7, lines 1 through 14. Finally, the results in Figure 2
`show less than 5 percent peptide degradation, but the claims are
`not so limited.
`With regard to Figure 3 and 4, we'll look at Figure 3
`first, there is little difference in the purity between the various
`bulking agents at room temperature and 60 degrees Celsius. To
`be clear, the purity range there needs to be examined. For
`example, purity ranges from 98.66 percent to 99.03 percent.
`JUDGE BONILLA: Let me ask you a question about
`example 2. What was the pH that was held there? What was the
`pH they were using? I think it's designated in example 2 as being
`pH 7.1 to 7.5. That's the above the 1 to 7 that's disclosed in
`Kornberg [sic]; is that right?
`MR. FEDOWITZ: Literally it is, but it's within --
`JUDGE BONILLA: But does Kornberg suggest that
`not only it would be 1 to 7, but that ideally you would want
`something lower than 7? Isn't that unexpected that you would be
`able to get that level of stability at something that's higher than 7?
`MR. FEDOWITZ: I don't think it says that it's
`unexpected or you would want something lower than 7. I think it
`discloses 1 to 7. And isn't there also disclosure of 4 to 8?
`MR. BLAKE: Yeah.
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`JUDGE BONILLA: There's disclosure of 4 to 8 in
`Kornberg?
`MR. FEDOWITZ: Osterberg discloses 4 to 8.
`JUDGE BONILLA: But Osterberg isn't talking about
`glucagon or GLP-2 analogs; is that correct?
`MR. FEDOWITZ: But it's talking about the use of
`histidine to stabilize the formulation. That's where you have this
`guidebook of how to use histidine. And Osterberg discloses the
`use and teaches 4 to 8. So there's overlap there. Just to be clear, I
`don't think it teaches away at all from using anything above or
`about 7. It just discloses the pH range from 1 to 7.
`JUDGE BONILLA: What is the interplay between
`teaching away and unexpected results? One would have expected
`this to work. Is that the same thing as considering teaching
`away?
`
`MR. FEDOWITZ: I don't think there's anything
`unexpected here. This is just data. With regard to how the
`example 2 discloses 7.1 to 7.4, the disclosure in Drucker '379
`discloses the full range from 1 to 7. So there's nothing -- I don't
`think it's dissuading anyone from using above a pH of 7. But
`with the bridge of Osterberg stating the use of pH 4 to 8, it
`alleviates that issue.
`JUDGE SNEDDEN: But there is a big difference
`between pH that glucagon was formulated and with what GLP-2
`was formulated at. And I think this kind of goes to the argument
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`that patent owner is stressing, which is you wouldn't necessarily
`look to glucagon to guide you to a formulation of GLP-2 due to
`several differences. One that impacts the formulation of
`pharmaceutical composition is pH. And I think one of the
`references you provided, Cleland, Exhibit 1024, noted that, that
`pH has a big determination impact on degradation pathways and
`potentially how you would formulate peptides.
`MR. FEDOWITZ: Yeah, I understand that. I'm just
`going from what the prior art discloses. And I just want to bring
`to your attention --
`JUDGE SNEDDEN: It does speak to why you would
`combine them, why you can rely on art that discloses -- that is
`focused on glucagon and have that as your guidance to a person
`of ordinary skill in the art as to what you would achieve with
`GLP-2. This change -- there's differences in pH.
`MR. FEDOWITZ: In Kornfelt, it discloses a range
`from 1 to 7. In that reference it says it's most stable at 2.8.
`However, it also provides the range from 1 to 7. In fact, if you
`look at the Munroe reference, there's a chart, I believe, at Table 5,
`it discloses glucagon at a pH of 6.0. So these pH ranges, the
`Munroe reference -- here it is. Or maybe it's Keiffer.
`JUDGE SNEDDEN: What page is that?
`JUDGE BONILLA: Which exhibit too, please?
`MR. FEDOWITZ: It's Exhibit 1019.
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`JUDGE BONILLA: Can you give a pinpoint cite in
`relationship to glucagon and pH 6?
`MR. FEDOWITZ: Yeah, I'll have it for you in just one
`
`second.
`
`JUDGE BONILLA: It would also be helpful to point
`out where you raise that in the papers, the issue about this
`reference.
`MR. FEDOWITZ: There you see glucagon is the fourth
`peptide down and to the right you see the pH of 6.0.
`Further, just with regard to Figures 3 and 4, there is no
`statistical analysis with regard to these data points 98.66 percent
`to 99.03. In addition, at 60 degrees Celsius the reported purity
`ranged from 89.5 to 94 percent, also no statistical analysis or any
`meaning being attributed to that. Because of this, there is no
`basis to allege that the purities differ or are even significant.
`Even though patent owners allege Kornfelt teaches mannitol and
`lactose are equivalent, there is no data in Kornfelt involving
`mannitol.
`JUDGE GREEN: I hate to do this to you, but can we go
`back to 1019 for just one second. There's nothing in this
`reference that talks about these being stabilized or anything else.
`They are just doing NMR studies, correct?
`MR. FEDOWITZ: I believe that's correct. This is
`disclosure, however, of glucagon at that pH.
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`JUDGE GREEN: But we don't know how stable it is or
`what the --
`MR. FEDOWITZ: With regard to this reference, that's
`correct. But I just want to be abundantly clear, with Kornfelt, the
`only reason it points out 2.8, because that was the most stable. It
`doesn't say that it's not stable at any other pH.
`JUDGE GREEN: I understand that. Even though
`glucagon -- I mean, you could formulate any peptide at a lot of
`different pHs, but how long you can have them sitting on your
`shelf for NMR, those are big differences, correct? Whether or not
`you could store this in your freezer, take it out a week later, put it
`back in the NMR, get the same kind of results, we don't know the
`answer to those questions.
`MR. FEDOWITZ: I understand that. The claims at
`issue, though, have no degradation parameters with regard to time
`or percent degradation. So they are not limited in that regard.
`There are certain claims 28 through 30 and I believe 41
`through 43 that are not part of this IPR that have those
`parameters, but these claims at issue do not. So any stability
`whatsoever is at play.
`JUDGE GREEN: But to a certain extent, a lot of your
`arguments are reasons to combine and why one would have done
`this. I mean, what some of the references were talking about, like
`Kornfelt, were stability and stabilizing a peptide or a protein
`formulation, correct?
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`MR. FEDOWITZ: Yeah. There's motivation to
`combine these.
`JUDGE GREEN: No, no, I understand. But to say,
`okay, we don't have to talk about stability but part of the reason to
`combine is the stability. So I do think stability is important to
`some extent because it speaks to the reasons you are combining
`these references.
`MR. FEDOWITZ: Yes, to the extent there's some
`stability, then you are absolutely correct. And I just wanted to
`point to the fact that there are two parameters. There's a time
`parameter and there's a percent degradation parameter. To the
`extent there's some sort of stability, then that's accurate. I'm not
`saying stability doesn't matter, but the motivation to combine is
`there.
`
`With regard to Figures 5 and 6, I just want to point out
`that there's no support for patent owner's statement that Kornfelt
`found mannitol and lactose to be equivalent in glucose
`formulations. There's simply no experimental data regarding
`mannitol and Kornfelt. Patent owner disregards Kornfelt's
`disclosure that amino acids such as histidine provide better
`stabilization. Further, they disregard the fact that Kornfelt did not
`test lysing.
`What's also important here is claim 1 of the '886 patent
`is directed to a sucrose formulation, but example 4 at column 9,
`lines 4 through 5 and Figure 5 describe sucrose as destabilizing
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`GLP-2. Patent owners can't ignore this data and now include
`sucrose in the majority of their claims if they teach against it.
`Patent owner can't ignore it and then rely on the data for
`unexpected results. It's a contrary opinion. In view of this, in
`view of all these deficiencies, little weight should be attributed to
`any of these alleged unexpected results as secondary
`considerations of nonobviousness.
`There are no complexities also in this patent. The '886
`patent does not recognize any of the complexities associated with
`the peptide formulation alleged by patent owner. The inventor of
`the '886 patent never emphasized these issues in order to provide
`a sufficient disclosure. The '886 --
`JUDGE BONILLA: Can I ask you a question that I'm
`interested in. Patent owner is indicating that protein degradation
`and the difference in ways glucagon and GLP-2 degrade is
`important. And they also suggest that Dr. Palmieri suggested it
`was effectively irrelevant. Is that correct? Is it your position that
`it's irrelevant?
`MR. FEDOWITZ: The fact is the focus is on the
`macrostructure. There may be different amino acids, but there
`are similar amino acids that act in a similar manner or may
`degrade in a similar manner.
`JUDGE BONILLA: Do you believe that the
`degradation pathways between the two peptides are different?
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