Amgen Inc. v. F. Hoffmann-LaRoche LTD et al
Filing
1370
DECLARATION re #1369 MOTION in Limine To Preclude Roche From Using Unreliable Computer-Generated Models Of Peg-EPO At Trial Due To Roche's Selective Production Only Of Models That Were Created For This Litigation (=DECLARATION OF RENEE DUBORD BROWN) by Amgen Inc.. (Attachments: #1 Exhibit 1#2 Exhibit 2#3 Exhibit 3#4 Exhibit 4#5 Exhibit 5#6 Errata 6#7 Exhibit 7#8 Exhibit 8#9 Exhibit 9#10 Exhibit 10#11 Exhibit 11#12 Exhibit 12#13 Exhibit 13#14 Exhibit 14#15 Exhibit 15#16 Exhibit 16)(Gottfried, Michael)
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Amgen Inc. v. F. Hoffmann-LaRoche LTD et al
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EXHIBIT 12
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USDC Depo : Jorgenson, William Portions HIGHLY CONFIDENTIAL 5/1812007 9 :02 :00 AM UNITED STATES DISTRICT COURT DISTRICT OF MASSACHUSETTS Civil Action No . 05-12237 WGY AMEN, INC ., 5 5 Plaintiff, vs . 8 ) DEPOSITION OF: ) WILLIAM L . JORGENSEN, ) Ph .D. ) ) )**HIGHLY CONFIDENTIAL** )***RESTRICTED ACCESS***
3 4
9 F. HOFFMANN-LA ROCHE LTD ., a ) CONTAINS ROCHE Swiss Company, ROCHE ) CONFIDENTIAL BLA/IND 10 DIAGNOSTICS GmbH, a German ) INFORMATION SUBJECT TO Company, and HOFFMANN-LA ) PROTECTIVE ORDER-LOCKED 11 ROCHE, INC ., A New Jersey ) ROOM ACCESS ONLY Corporation, 12 13 Defendants . ) 14 15 TRANSCRIPT of the stenographic notes of the 16 proceedings in the above-entitled matter, as taken by 17 and before LISA FORLANO, RMR, CRR, CSR, CLNR, Notary 18 Public, held at the offices of Duane, Morris, 1540 19 Broadway, New York, New York, on Friday, May 18, 20 2007, commencing at 9 :02 a .m. 21 22 23 24 25
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(This transcript contains Confidential BLA/IND Information . Please treat the entire transcript in accordance with the
Amended Protective Order in this matter .)
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USDC - Depo : Jorgenson, William Portions HIGHLY CONFIDENTIAL 511812007 9 :02 :00 AM Appearances: 2 3 DAY CASEBEER MADRID & BATCHELDER BY : ROBERT M . GALVIN, ESQUIRE
KATIE J .L . SCOTT, ESQUIRE 20300 Stevens Creek Blvd ., Suite 400 5 Cupertino, California 95014 (408) 873-0110 6 galvinrm@daycasebeer .com kscoft@daycasebeer .com 7 Attorneys for Plaintiffs, Amgen
KAYE SCHOLER LLP BY : THOMAS FLEMING, ESQUIRE 10 425 Park Avenue New York, New York 10.022-3598 11 (212) 836-7031 e-mail : ffleming kayescholer.com 12 13 14 15 15 17 18 19 20 21
22 23 24 25
Attorneys for Defendant F . Hoffmann-La Roche
Also present: Nicholas Guzman, Videographer
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USDC Depo : Jorgenson, William Portions HIGHLY CONFIDENTIAL 5/18/2007 9 :02 :00 AM Q Do you consider computer modeling an 2 experiment? . .A 4 5 6 7
8
don't use it in that way . Some
people nowadays do. Q So using experiments in a way that would exclude computer modeling for the moment, you haven't performed any experiments with any pegylated
proteins, correct?
9 10 Q
Correct. Prior to your involvement in this case,
had you ever developed a computer model for the 12 structure of EPO? 13 14 A No. Q Prior to your involvement in this case,
15 had you ever developed a computer model for the 18 17 18 structure of any pegylated protein? No. is it fair to say, then, that the only
19 modeling work that you've done with respect to EPO 20 or pegylated protein is in connection with the work 21 22 you did for your expert report? MR . FLEMING : Objection . You have to
23 allow me to24 25 THE WITNESS: Okay . Yes. MR . FLEMING : Objection, vague to the Page 27
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term pegylated protein, ambiguous . Go ahead. 2 BY R . GALVIN: Q 4 5
6 7 8
Using the definition of experiments,
excluding computer modeling for the moment, did you perform any experiments in connection with
formulating your opinions for this case? No. You did, however, do some computer modeling or simulation work in connection with your
10 11 12
expert report, correct? Correct. Did you ask Roche -- withdraw that.
13
Are you aware of any internal efforts
14 by Roche to model, develop computer models for CERA? 15 A No. You understand that Roche is one of the 17 largest pharmaceutical companies in the world, 18 correct? 19
20
A Yes.
Q And you know that Roche has experts
21
like you who are experts in the field of
22 computational chemistry, correct? 23 MR . FLEMING : Objection, assumes facts
24 not in evidence. 25 THE WITNESS: I`m not sure if they would
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USDC - Depo : -Jorgenson, William Portions HIGHLY CONFIDENTIAL 5/18/2007 9 :02 :00 AM know, with respect to this expert report . So have 2 3 4 5 6 taken EPO beta as a reagent and have not read or reviewed a lot on the characterization of EPO beta. Q You understand, although you may not know the specifics, that epoetin beta has a particular confirmation? MR. FLEMING : Objection to form. THE WITNESS : Proteins in general can 9 10 II have confirmation and it can proteins have primary, secondary and tertiary structure . The tertiary structure is sensitive to the environment,
12 the conditions . So sometimes it can be more in a 13 foded state, sometimes it can be in a less folded 14 state, depending on the conditions.
15 BY MR . GALVIN: Q Did you consider in forming your
17 opinions whether the pegylation reaction caused the 18 structural confirmation for the EPO polypeptide 19 backbone to refold or reorganize as a result of 20 pegylation? 21 22 23 24 MR . . FLEMING : Objection, vague, mischaracterizes his opinion. THE WITNESS : As mention in my report, there is no reliable, accurate, experimental data on
25 the structure of CERA. Amgen v . Roche Page 125
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USDC Depo : Jorgenson, William Portions HIGHLY CONFIDENTIAL 511812007 0 :02:00 AM BY MR. GALVIN:
Can the --
3
A The three-dimensional structure of CERA meant there. Q Can aspects of the three-dimensional
6 7 8 9 10 11
structure of CERA be inferred as a result of its biological activity? MR . FLEMING : Objection, beyond the scope of his report. THE WITNESS : I, in my report, I address the binding issue and also in my report provide my
12 own model of the three-dimensional structure of CERA
13 and we can discuss those . feel that my model is 14 consistent with the binding data.
15 BY MR . GALVIN: 16 In order to bind to the EPO-receptor
17 CERA must have a particular confirmation, correct? 18 19 MR . FLEMING : Objection. THE WITNESS: would say no.
20 BY MR . GALVIN: 21 Q Does the -- does the fact that CERA
22 binds to the EPO-receptor allow one to deduce 23 anything about the structure of CERA? 24 25 MR . FLEMING : Objection, vague. THE WITNESS: I think that's -- your
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question is too vague . I think you have to rephrase it BY MR . Q AL' IN: Does CERA specifically bind to the
5
EPO-receptor? MR . FLEMING : Objection, beyond the
7 8 9 10 II 12
scope of his report. THE WITNESS : The Lodish report. and in Lodish where he refers to Roche documents, there's evidence that CERA binds- to the EPO-receptor.
BY MR . CALVIN :
0 And are you aware of other molecules in
13 the human body that bind and activate the 14 EPO-receptor other than EPO? 15 1 17 18 19 MR . FLEMING : Objection, beyond the scope of his report. THE WITNESS : That is again beyond the scope of my report. 1 stated in particular with regard to the binding data that there is data that, a
20 form of EPO and CERA bind to the EPO-receptor. 21 BY MR . GALVIN: 22 Q Let me try it this way . Suppose you
23 took the PEG starting reagent used to make CERA and 24 you placed it in solution with the human 25 EPO-receptor, would you -- would you expect to Page 127
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observe specific binding of the PEG reagent to the 2 EPO-receptor? MR . FLEMING : Objection, incomplete 4 hypothetical.
THE WITNESS : 6 7 8 9 10 have no data that I've
seen discussing that . The PEG-EPO reagent is an activated reagent and it is a reactive molecule. There are a lot of things that could happen to it in an experiment such as the one you suggest . don't think would last very long.
11 BY MR . GALVIN: 12 0 Are you aware of any data or
13 experiments which would establish that the 14 15 16 structural confirmation of the epoetin beta starting material would be substantially different after the pegylation reaction?
17 18
MR . FLEMING : Objection to form. THE WITNESS: You don't. have a
1.9 three-dimensional structure of CERA . CERA is a 20 unique, much larger molecule than the EPO beta 21 22 reagent . So all bets are off. I'd say, you know, in any -- I can't have a detailed discussion of the
23 structural of the structure of CERA without -- in 24 the absence of the experimental data, so -25 BY MR . GALVIN:
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USDC - Depo : Jorgenson, William Portions HIGHLY CONFIDENTIAL 511812007 9 :02 :00 AM 1 2 3 4 5 6 7 atoms in the molecule are known. Based upon your review, are you have you identified any errors in the identity, number and sequence of atoms in the CERA molecule depicted by Dr. Lodish or is it primarily an issue with respect to the structural confirmation of it that you criticize? A The level of the model is so crude that 9 10 11 1 wouldn't be able to distinguish if there were errors. Q The next sentence on page 53, what is
12 not known about. CERA, however, is its 13 14. 15 three-dimensional structure or confirmation, the overall shape of the molecule. So isn't it the case, Dr. Jorgensen,
15 that today no one really knows the three-dimensional 17 structure of CERA, correct? 18 A Yes . li ve stated that, that there is
19 no more experimental structure that people would 20 consider to be reliable for CERA. 21 Q And based upon the current data
22 available, no model would have a degree of high 23 24 25 reliability in terms of accurately depicting the molecule as it would exist in solution, correct? MR . FLEMING : Objection. Page 169
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USOC Depo : Jorgenson, William Portions HIGHLY CONFIDENTIAL 5/18/2007 9 :02 :00 AM THE WITNESS : No model is a, you know, 2 3 4 5 pretty all encompassing term . believe we could create a model that would have faith in, . that it was a reasonable depiction of CERA, you know, if I was given the time to do it. BY MR . GALVIN: And do you believe that the pictures 8 that you generated for purposes of this report would satisfy that standard? 10 11 A No . said that they're a starting
point and think that the -- in a short period of
12 time, we gave it a good shot . There's nothing 13 fundamentally wrong in what we did, but it is 14 lacking in a number of areas I'm happy to discuss. 15 Q You don't know how long, if at all,
15 Roche has been developing models for CERA, correct? 17 A No, we've talked about that before.
18 I'm not aware that they have done anything in the 19 way of modeling of CERA. 20 21 Q In attempting to model the structure of
CERA, given the limits of our current knowledge,
22 would you agree that an appropriate starting place 23 would be to use data from the characterization of 24 EPO? 25 Amgen v. Roche MR . FLEMING : Objection. Page 170
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USDC Depo : Jorgenson, William Portions HIGHLY CONFIDENTIAL 5118/2007 9 :02 :00 AM 1 2 THE WITNESS : I dora know what you mean data, what data and what characterization?
3 BY MR . GALVIN: 4 5 6 7 8 A NMR or X-ray crystallography ordinance. In our own, you know, limited work on
modeling CERA we did start with the NMR structure that is deposited in the Protein Data Bank . We do need to start with the structure . In the types of simulations we can do, however, we can do enough
10 11 12 13 14
sampling to can try to explain that, to let that system evolve so that the detail of the starting point for the more sophisticated calculations we do would not be critical. Q Now, earlier you said that you tended
15 to prefer Xray crystallography over NMR . Why did 16 you choose NMR as the basis for building the model 17 of GERA? 18 A We chose the NMR structure because it's
19 the only one that I saw in the Protein Data Bank for 20 the uncomplexed, an uncomplexed EPO analog. 21 Q Now, if you were attempting to model
22 the binding complex of CERA to the EPO-receptor, 23 would you prefer then to use the X-ray 24 crystallography data as opposed to the NMR data? 25 A Yes.
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1JMC Depo : Jorgenson, William Portions HIGHLY CONFIDENTIAL 5/18/2007 9 :02 :00 AM Q And you understand that one of the 2 3 4 points that Dr. Lodish was trying to illustrate was binding of GERA to the EPO-receptor, correct? MR . FLEMING : Objection to form. THE WITNESS: I'm not sure what exactly 6 7 8 9 he was trying to mean can give you my opinion of what he was trying to illustrate. There were graphics that showed an image of the complex as in the Eyed paper.
10 BY MR . GALVIN: 11 12 Q And so depending on whether you're trying to illustrate or depict a -complex . EPO, an
13 EPO-receptor or CERA, an EPO-receptor versus EPO or 14 GERA in an unbound state, you might prefer the NMR 15 data or the X-ray crystallography data as your 16 17 18 starting point, correct? MR . FLEMING : Objection. THE WITNESS : The information that's
19 available the Protein Data Bank for this system is 20 limited and we were interested in the uncomplexed EPO 21 and it was a reasonable starting point . for us to use
22 the NMR structure . If we were to try to model the 23 complex given what's in the Protein Data Bank, I 24 would pick some structure of the complex . The 25 complex is too big to do NMR, so we would have to use
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USDC - Depo : Jorgenson, William Portions HIGHLY CONFIDENTIAL 5/18/2007 9 :02 :00 AM some X-ray structure. 2 BY MR . GALVIN: 3 4 5 6 7 8 Q If you could turn to Paragraph 129.
I'd like to, for you to just explain once you imported in the NM structure for EPO, when you added the 600 ethylene oxy units around the EPO, did you predefine a shape by which the ethylene oxy units would be added? Can you expand on shape?
10 11
Sure . When you generated the image or the starting point for the modeling, did you
12 randomly assign ethylene gylcols at any random . 13 position or did you define a sphere or some sort of 14 shape and then populate that shape initially with
15 ethylene gylcols before the simulation began? 15 17 MR . FLEMING : Objection. THE WITNESS : We the work we did on
18 this we did in about a day, two days . So we didn't 19 put a lot of effort into it . We actually built the
20 CERA model in a couple of ways . The one felt 21 22 easiest to describe here was something that I cooked up just for thin where took ethylene oxy units of
23 CH2, CH20 and basically they were randomly placed in 24 a volume surrounding the NM structure of the EPO
25 mutant . And then
don't know how much detail you
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USDC - Depo : Jorgenson, William Portions HIGHLY CONFIDENTIAL 5118/2007 9 :02 :00 AM want to go in on this, but these units were then 2 3 linked together and we attached them to the N-terminal, nitrogen of the EPO mutant.
4 BY MR . GALVIN: Q Maybe it will be helpful at this point.
to look at Exhibit 2 of your deposition, which is 7 8 9 10 11 12 Q Exhibit C . It's the other document we haven't looked at yet which has all your demonstratives. Uh-huh. And fortunately, they're not exactly
numbered, so we'll try to be clear when we talk about these to describe points . I'd like to turn to
13 the picture of the model . Maybe we could turn to 14 the picture of this model that you developed and 15 this is the one with all the beads, but you can see 16 17 18 19 the blue and green structures in the center. It's a large view, about halfway in. A This one? Q Yes . So what does the blue and green
20 represent? 21 A 0 my tutorial part of my report,
22 mention that there were very many different ways of 23 what we call rendering molecules, so at the base of 24 any drawing like this graphic, there is a set of
25 cartesian coordinates, XYZ coordinates . Now you
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then, you make the thing look in terms of balls and 2 3 4 5 6
7 8
other pretty entities, the sizes of the balls is -- there are arbitrary decisions that are made . In the case this is a model of CERA that I feel pretty good about . To me the model makes sense . The blue part are helices and the CERA is a biopolymer and it
has amino acid residues and one often represents amino acid residues in many different ways, but if
9 10 11 12
there are helices, then you can show them in these helical ribbon forms . That's what the blue is. Q And the blue and green is supposed to indicate the -- well, the blue and green is derived
13 from the EPO NMR data in the Protein Data Bank that 14 was reported by Cheetham, right? 15 16 17 MR . FLEMING : Objection, the term derived, vague. THE WITNESS : Yeah, CERA is a biopolymer
18 that contains some amino acid residue, so we have 19 shown amino acid residues that appear to be in 20 helices in the blue ribbons and the green are amino 21 acid residues that are in less structure, in this
22 sense a secondary structure which we call loops. 23 BY MR . CALVIN: 24 Q In the amino acid sequence that you are
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USDC Depo : Jorgenson, William Portions HIGHLY CONFIDENTIAL 5118/2007 9 :02 :00 AM of human EPO sequence? Yeah . We started, as I mentioned 3 4 5 6 7
8
earlier, from the BUY coordinates that are deposited in the Protein Data Bank . And we were able to build a model of CERA, you know, with the aid of that . I don't, as I say here, I don't swear that this is . Well, you know, this is just my
attempt to have an alternative to the models that
9 10 11 12 13
were done by Dr. Lodish . I feel we could do a much better job on this, you know, letting it relax, adding water, adding counter ions . We may well do that. Now, you don't depict in your model,
14 you don't attempt to model the carbohydrate 15 structure of CERA, correct? 16 17 18 19
20
MR . FLEMING : Objection, assumes facts not in evidence. THE WITNESS : This was a model that I again didn't build just to illustrate that there was
nothing special or legitimate about the Lodish model
21
and that I could create a comparable or potentially
22 more detailed model than Dr . Lodish provided.
23 BY MR . GALVIN: 24 Q But it doesn't -- your model doesn't
25 show carbohydrate structures, correct?
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USDC Depo : Jorgenson, William Portions HIGHLY CONFIDENTIAL 5/18/2007 9 :02 :00 AM
A This model does not have any sugar 2 residues. -Q
4
Now, for lack of a better way of
describing it, you've visualized and depicted the
5
PEG surrendering the amino acid residues, correct? MR . FLEMING : Objection, vague,
7
mischaracterizes the term surrounding, THE . WITNESS : We didn't -- we didn't
9
deliberately do anything here other than, you know,
10 we started with a set up, which was in one version, 11 12 3 14 which this figure and the other figure look the same. added the ethylene oxzyene and then I they were annealed, if you will, random Monte Carlo statistical simulation to relax the ethylene oxy units and then
15 we turned on some forces between them to build it 1 into a contiguous chain of the ethylene oxy units.
17 BY MR . GALVIN: 18 19 Q Would you expect that for GERA to maintain in this spherical-like confirmation at all
20 times or is this one snapshot in time? 21 22 I really don't want you or anybody else to over interpret the significance of this picture.
23 We haven't worked on it. This is not publishable,
24 let me put it that way . I would never try to write
25
this up and send it into a journal, you know . With
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USDC Depo: Jorgenson, William Portions HIGHLY CONFIDENTIAL 5/18/2007 9 :02 :00 AM more work, we could get something published . This 2 3 4 5 6 7 8 9 10 11 12 13 is a nice starting point . We would really need to run a simulation . Like I said, we had water, we had counter ions, we'd run it for a long time, a micro dynamic simulation and we would do a solid scientific state of the art simulation job, you know, on this system . And we would probably work on some other systems, too, you know, and try to get, you know, my curiosity is now peaked about molecules like CERA . But I think what you see here, and if you maybe squint a little is what I think is a reasonable picture as opposed to their cartoon, we'll even call it, compared to the Lodish picture,
14 which I think is completely unreasonable and 15 16 17 18 19 20 21 inconsistent with the facts. Q Now,. if you turn to the next . page in
Exhibit 2, which is another depiction of one of your structures and it's titled : "A Likely Ro50-3821 Structure (static)". What's the difference between the two pictures we looked at? Is the first one a cutaway
22 view? 23 A No, a good question . Just the
24 rendering, what call a rendering, we've now shown 25 all atoms in what I call CPK colors, which is red Amgen v . Roche
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USX. Depo : Jorgenson, William Portions HIGHLY CONFIDENTIAL 5/1812007 9:02 :00 AM for oxygens, blue for nitrogens, gray for carbons. 2 3 4 5 6 7 8 9 10 11 We haven't shown hydrogens in our model . We have the hydrogens in the coordinate file that we provided . You'll see there are hydrogens there as well . This is just now a rendering where all of the atoms are rendered as spheres and there are some size differences depending on the radii of the atoms . The little yellow dot is a sulfur and a cysteine ermathamine residue. Now, looking at -MR . FLEMING : Could you just hold that
12 up to the camera so the jury can see what you're 13 talking about? Thank you.
14 BY MR . GALVIN: 15 16 17 18 19
20
Q
Looking at the caption here, A Likely
Ro50-3821 Structure, what level of certainty do you have sitting here today that this is a likely structure? A feel it is a -- compared to the
Ladish structure, I'm going to call it likely . For
21 one thing, as you mentioned, we are -- CERA, we 22 believe there is glycosylate . We don't have that.
23 R 503821 is GERA . So I mean there is some 24 25 Amgen v . Roche differences like that. On the other hand, I do believe that
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the general features here are consistent with my knowledge of what I: expect with the result of a reaction or one pegylates a protein. Q So if we go back to the other slide,
the first slide we looked at which shows the ribbon structure. A L1h-huh. Does your depiction show the point of
9
attachment between PEG, the polyethylene glycols and
10 the amino acid residues? 11 MR . FLEMING: Objection, vague,
12 objection to the term attachment. 13 14 5 16 THE WITNESS : To make this, as we talked, the pegylation reaction either uses a nitrogen of the lysine or nitrogen of the N .-terminal residue of the protein reagent . In this case, we
17 have used the N- terminus of the protein reagent to 18 19 yield this illustration of potential product from a pegylation reaction.
20 BY MR . GALVIN: 21 22 Q And so in your depiction here, although
just visually to a lay person you see these poly
23 these little balls for the peg around, it's only 24 actually bound and attached to the amino acid 25 residues, the green and blue at one location in your Amgen v. Roche
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USDC Depo : Jorgenson, William Portions HIGHLY CONFIDENTIAL 5/1812007 9 :02 :00 AM :model? MR . FLEMING : Objection. THE. WITNESS : There is a bond between 4 5 the N-terminus of the protein reagent effectively and the PEG reagent. So this is again our shot at a very crude mods of CERA without the sugars, not any sugars . There is a bond length, . if you look at detail at our coordinates, you'll see that there is a bond. BY SIR . CALVIN Now-A 0 An amide bond. Can CERA bind to the EPO-receptor and
6
7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23
initiate signaling in this confirmation that you depict in your model? MR . FLEMING : Objection. THE WITNESS : don't know what the
structure is of GERA in solution . This is a cartoon and we need to work on it more and I don't know the structure of the complex of the EPO-receptor with SERA, So anything beyond that is conjecture. BY MR. GALVIN : Q Would your expectation be that when
24 CERA binds to the EPO-receptor there are all of 25 these ethylene gylcols between the amino acid
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U C Repo : Jorgenson, William Portions HIGHLY CONFIDENTIAL 511812007 9 :02 :00 AM 1 and we're back on the record.
2 BY MR . ALV1N: Q 4 b 6 7 Dr. Jorgensen, one of the questions
going back a ways when I asked you about how you originally arrayed the ethylene gylcols when you were developing your model, you said you randomly filed the volume, what was the shape of that
3 volume? 9 10 11 12 13 14 Q A sphere. And was this sphere centered around the
center point of the EPO N R structure that you started with? A More or less. Q And what was the basis for your
15 assumption that the pegylation would be arrayed or .16 at least that would be a reasonable place to begin 17 your modeling from? 18 A Nothing in particular except it's a
19 sort of standard feature we have in the software 20 where we can add a solvent around a solute, what we 21 call a solute and generally one puts that in a
22 spherical shape or in a cubic shape. 23 Q And why wouldn't you start and center
2.4 that sphere if you were going to use a sphere around 25 the point where the amide bond would be between the
ven . Roche Amg
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USDC Depo : Jorgenson, William Portions HIGHLY CONFIDENTIAL 511812007 9 :02 :00 AM 1 ethylene gylcols and the NMR and EPO structure?
MR . FLEMING : Objection to form. 3 BY MR . GALVIN: Q 5 6 7 8 9 In other words, haven't you biased it
by assuming it would be equally distributed from the center of the molecule as opposed to centering it from a point of attachment?
MR . FLEMING : Objection to form.
THE WITNESS: Al'l we've done here is
0 created an image that's an alternative to the image 11 that was provided in the Lodish report . What said
12 is, if we were given time, we would like to do a 13 14 better job ., let the system fully equilibrate and we could start, have different starting points and see
15 where, if they equilibrate to a common point . So 1 17 18 it's very preliminary and as mentioned, I said to illustrate the point on page -- Paragraph 129, to illustrate the point that one can create alternative
19 images for CERA, I provided the attached sample. 20 Mars really what we were doing here. 21 BY MR . GALVIN: 22 ' Q Another point that you mentioned before
23 the break was that you hadn't received or reviewed 24 data coordinate files relating to the model 25 generated by Dr. Lodish . Is it your understanding Amgen v . Roche
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USDC Repo: Jorgenson, William Portions HIGHLY CONFIDENTIAL 5/1812007 9:02 :00 AM report, as think I mentioned very early on felt to
2 be redundant or irrelevant.
3 4
Q Can you turn to page 358. MR . FLEMING : Of his report?
5 BY MR . GALVIN: Q Of your report, Paragraph 136 of your 7
8
report . And this is the section where you critique
Dr. Lodish's depiction of the carbohydrate
9
structure . Now, as you noted, Dr . Lodish
10 acknowledged that the choices of how to actually 11
12
make a depiction was uncertain . There was no
experimental basis for drawing a structure . He
13 14 15 18 17 18 19 20 21
identified that fact if his report, correct? MR . FLEMING : Objection to form. THE WITNESS : I say in Paragraph 135 says : Dr . Lodish himself recognized, however, the choice of carbohydrates is uncertain. MR . FLEMING : Start over. THE WITNESS: I'm quoting from Paragraph 135 of my report . As Dr. Lodish himself recognizes, however, the choice of carbohydrates is uncertain and
22 the coordinates of these carbohydrate chains have not 23 been obtained using currently available experimental
24 techniques. 25 BY MR . GALVIN: Roche
Amgen
V.
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Q 2 3
4
So the scientific truth here is that no
one knows how to accurately represent a 3D representation of the attached carbohydrates of -attached to either GERA or EPO based on our current
state of knowledge, is that fair? 6 MR . FLEMING : Objection to form . THE WITNESS: Yes . There's uncertainty
8 about the carbohydrates.
9 BY MR . GALVIN: .10
Q
But nevertheless, we know that the
11
carbohydrates have a role and are present on the
12 CERA molecule, correct? 13 MR . FLEMING : Objection, beyond the
14 scope of his report. 15 16 THE. WITNESS : Yes, don't know that they have a role . I believe they're present.
17 BY MR . GALVIN: 18 Q You don't know whether they play --
19 they have a role in protecting the molecule from 20 proteases? 21 A No, that's definitely outside of this.
22 Any discussion of carbohydrates is really outside 23 the scope of my report and I know there are 24 carbohydrate experts that are involved in this. 25 Q But you don't consider yourself an
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USDC - Depo : Jorgenson, William Portions HIGHLY CONFIDENTIAL 5118/2007 9 :02 :00 AM
1 2 3 4 5 6 7 8 9 10 11 12 13 14
JURAT
I, WILLIAM L . JORGENSEN, Ph .D ., the witness herein, the foregoing testimony of the pages of this deposition, do hereby certify it to be a true and correct transcript, subject to the corrections, if any, shown on the attached page.
WILLIAM L . JORGENSEN, Ph .D.
15 Subscribed and Sworn to before me 16 17 18 19 20 21 22 23 24 25 Notary Public this day of 2007.
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