Amgen Inc. v. F. Hoffmann-LaRoche LTD et al

Filing 744

DECLARATION re #743 Memorandum in Opposition to Motion, #741 MOTION to Strike , In the Alternative, Untimely Expert Testimony of Ralph A. Bradshaw Regarding Amgen's Motion for Summary Judgment of No Obviousness-Type Double Patenting (by Timothy M. Murphy) by F. Hoffmann-LaRoche LTD, Roche Diagnostics GmbH, Hoffmann LaRoche Inc.. (Attachments: #1 Exhibit A#2 Exhibit B#3 Exhibit C#4 Exhibit D#5 Exhibit E#6 Exhibit F#7 Exhibit G#8 Exhibit H)(Toms, Keith)

Amgen Inc. v. F. Hoffmann-LaRoche LTD et al

Doc. 744 Att. 4

Case 1:05-cv-12237-WGY

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EXHIBIT D

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Bradshaw, Ph. D., Ralph 6/19/2007 Amgen Confidential and Roche Restricted Access - BLA/IND Material Page 1 UNITED STATES DISTRICT COURT DISTRICT OF MASSACHUSETTS --ooOoo-AMGEN INC., ) ) Plaintiff, ) ) vs. ) ) F. HOFFMAN-LA ROCHE, LTD., ) ROCHE DIAGNOSTICS, GmbH, and ) HOFFMAN-LA ROCHE, INC., ) ) Defendants. ) ______________________________)

No. 05-CV-12237 WGY

Videotaped Deposition of RALPH BRADSHAW, Ph.D. TUESDAY, JUNE 19, 2007 (Contains Amgen Confidential and Roche Restricted Access Confidential Information BLA/IND Material Subject To Protective Order.)

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SHEILA CHASE & ASSOCIATES REPORTING ON BEHALF OF LIVENOTE WORLD SERVICE 221 Main Street, Suite 1250 San Francisco, CA 94105 Reported by: DIANA NOBRIGA, CSR, CRR LICENSE NO. 7071 LiveNote World Service 800.548.3668 EXT. 1

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1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 BE IT REMEMBERED that, pursuant to Notice of Taking Deposition, and on TUESDAY, JUNE 19, 2007, commencing at the hour of 9:06 a.m., thereof at LiveNote, 221 Main Street, Suite 1250, San Francisco, CA 94105, before me, DIANA NOBRIGA, a Certified Shorthand Reporter in and for the State of California, personally appeared RALPH BRADSHAW, Ph.D., called as a witness by the defendants, who being by me first duly sworn, was thereupon examined and testified as hereinafter set forth. ---

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INDEX DEPOSITION OF RALPH BRADSHAW, Ph.D. TUESDAY, JUNE 19, 2007 EXAMINATION BY: Page MR. JAGOE 7, 296 MS. CARTER 294 EXHIBITS Page Exhibit 1 (Contains Amgen Confidential Information Subject to Protective Order) Rebuttal Report of Ralph A. Bradshaw, Ph.D. 40 Exhibit 2 (Contains Amgen Confidential and Roche Restricted Access Confidential Information BLA/IND Material Subject to Protective Order) Rebuttal Report of Ralph A. Bradshaw, Ph.D. to New Non-Infringement Arguments Raised in the Rebuttal Reports of Defendants' Experts 40 Exhibit 3 The Amino Acid Sequence of the y-Subunit of Mouse Submaxillary Gland 7 S Nerve Growth Factor 97
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1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 APPEARANCES FOR THE PLAINTIFF AND WITNESS: KRISTA CARTER, ESQ. DAY CASEBEER MADRID & BATCHELDER, LLP 20300 Stevens Creek Blvd., Suite 400 Cupertino, CA 95014 [phone] [e-mail] FOR THE DEFENDANTS: CHRISTOPHER T. JAGOE, ESQ. KAYE SCHOLER, LLP 425 Park Avenue New York, NY 10022-3598 [phone] [e-mail] ALSO PRESENT: JAKE KROHN, VIDEOGRAPHER

Exhibit 4 United States Patent No. 4,667,016 177 Exhibit 5 Purification of Human Erythropoietin 258 Exhibit 6 Sugar profiling proves that human serum erythropoietin differs from recombinant human erythropoietin 278 Exhibit 7 United States Patent No. 4,703,008 295 Exhibit 8 United States Patent No. 5,621,080 295 Exhibit 9 United States Patent No. 5,618,698 296 Exhibit 10 United States Patent No. 5,756,349 296 Exhibit 11 United States Patent No. 5,441,868 296 Exhibit 12 United States Patent No. 5,955,422 296 Exhibit 13 United States Patent No. 5,547,933 296 ---oOo---

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VIDEOGRAPHER: Here begins the videotaped deposition of Ralph Bradshaw, tape one, Volume I, in the matter of Amgen, Inc. versus F. Hoffman-La Roche Limited, et al., in the United States District Court, District of Massachusetts, Case No. 05-12237 WGY. Today's date is June 19th, 2007 and the time on the video monitor is 9:06. The video operator today is Jake Krohn, representing LiveNote World Service, located at 221 Main Street, Suite 1250, San Francisco, California 94105, phone number 415 321-2300. The court reporter is Diane Nobriga of Sheila Chase, reporting on behalf of LiveNote World Service. Today's deposition is being taken on behalf of the defendant and is taking place at 221 Main Street, Suite 1250, San Francisco, California 94105. Counsel, please introduce yourselves and state whom you represent. MR. JAGOE: Christopher Jagoe from Kaye Scholer, representing the defendants. MS. CARTER: Krista Carter of Day Casebeer on behalf of Amgen and Dr. Bradshaw. VIDEOGRAPHER: Okay. You can swear the witness. Page 7

this case, signed your first expert report in this case?) MR. JAGOE: Do you need clarification of that? MS. CARTER: Dr. Bradshaw is here as an independent expert. Day Casebeer represents Amgen. THE WITNESS: I'm trying to remember the chronology. My initial contact with this case was with Linda Baxley. At what point I also began to deal with counselor, I don't remember exactly. Sometime in the last two months, I would say. MR. JAGOE: Q. Did you make any arrangements with the Day Casebeer law firm where they would act as your attorneys during the pendency of this case? A. Day Casebeer contracted with me to be an expert witness in this case. Q. And are you acting as an expert on behalf of Amgen? MS. CARTER: Objection. THE WITNESS: I was contracted with Day Casebeer under the understanding that I am representing Amgen, yes. MR. JAGOE: Q. The testimony you are giving in this deposition is testimony on behalf of Amgen; correct? MS. CARTER: Objection; Dr. Bradshaw is an
Page 9 independent expert. THE WITNESS: I'm giving an expert opinion based on the information that Day Casebeer asked me to opine on. MR. JAGOE: Q. And Day Casebeer is paying you to give the opinions that you're going to give; right? A. I'm being reimbursed for my services, yes. Q. You are being reimbursed by Day Casebeer; is that correct? A. Since I haven't been reimbursed, I'm not actually sure who is writing the checks. Q. You have an agreement with Day Casebeer that you will be reimbursed by them for giving your opinions in this case? MS. CARTER: Objection; he's not being reimbursed for his opinions. It's for his time. THE WITNESS: I'm being reimbursed for my time in this case, yes. MR. JAGOE: Q. By whom? A. Could you clarify the question, by whom? Q. By whom will you be reimbursed for the time spent giving opinions in this case? MS. CARTER: Asked and answered. THE WITNESS: I don't have any information who will write the actual check.

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RALPH BRADSHAW, Ph.D., having been duly sworn, testified as follows: EXAMINATION BY MR. JAGOE MR. JAGOE: Q. Dr. Bradshaw, is Ms. Carter representing you today? A. Yes, she is. Q. Are you paying her for that representation? MS. CARTER: Objection. THE WITNESS: No, I'm not. MR. JAGOE: Q. When did you first understand that she was representing you? MS. CARTER: Objection; calls for a legal conclusion. THE WITNESS: I think about a month ago. MR. JAGOE: Q. Was that before you served your first expert report in this case, signed your first expert report in this case? MS. CARTER: Objection; I don't know that he understands the meaning of me representing him. THE WITNESS: Yes. Could you qualify the question. MR. JAGOE: What's the pending question that I'm qualifying? (Record read as follows: QUESTION: Was that before you served your first expert report in

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MS. CARTER: Objection; outside the scope of his expert report. THE WITNESS: I just don't have an opinion. MR. JAGOE: Q. Do you agree with the statement that treatment of urinary EPO with phenol will reduce the number of branches of each of the asparagine type sugar chains? MS. CARTER: Objection; outside the scope of his expert report, incomplete hypothetical. THE WITNESS: I have no personal knowledge about that. I couldn't answer that question. MR. JAGOE: Q. Do you have any expert opinion about that? A. Beyond the scope of anything I've ever done. I may be an expert, but it doesn't mean I have done everything there is to do, including chemistry. And I've never used a phenol extraction to make a protein cell. I really have no idea whether phenol affects glycoproteins. Q. But you are offering an opinion about the Miyake procedure which used a phenol extraction method? A. The opinion I offered, I believe, if you check what I said, was that Dr. Goldwasser felt that's what phenol did. Q. Do you have an opinion whether phenol will Page 171

time. I can't give you a specific example of another application of this type. Q. So before forming your opinion that the statement in the Lin patent that a C4 column could be used to purify EPO, you never checked the prior art literature on the use of C4 columns to purify proteins? A. I didn't need to. C4 columns were used to purify proteins. Just because I can't cite you an example doesn't mean I'm not aware they were used. Q. Did you cite any articles in your expert report where a protein was purified by a C4 column? A. I don't believe I did, no. Q. Would you agree with the statement that prior to 1985 only a single reference is known to exist disclosing the elution of a protein with ethanol from a C4 column? MS. CARTER: Objection. Could you read the question again. MR. JAGOE: Can you read it, please. (Record read as follows: QUESTION: Would you agree with the statement that prior to 1985 only a single reference is known to exist disclosing the elution of a protein with ethanol from a C4 column?) MS. CARTER: Objection; outside the scope of
Page 173 the expert report and lacks foundation. THE WITNESS: I can't comment on the statement, because I have no knowledge to know whether the statement is true or not. MR. JAGOE: Q. You just submitted a declaration about the Lai '016 patent; right? A. Yes, that's correct. Q. Did you read the Lai '016 patent before you submitted the declaration? A. Yes, I did. Q. Did the Lai '016 patent say anything about the state of the art of eluting proteins from C4 columns with ethanol gradients? MS. CARTER: Objection. I don't think Dr. Bradshaw was required to memorize the materials he reviewed. THE WITNESS: I did not read the Lai patent with respect to the previous literature. He cites some previous literature, he cites the Lin patents. But I did not bother to read the backgrounds with respect to other possible applications of C4 prior to the Lai or Lin patents. MR. JAGOE: Q. So you formed the opinion that the Lai patent was a novel, nonobvious method, and you didn't review what prior art existed about purification

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cause a reduction in the number of branches of the asparagine type sugar chains on the erythropoietin? MS. CARTER: Objection; outside the scope of his expert report. THE WITNESS: I don't have any opinion at all. I'm not familiar with phenol and glycoprotein stability, so I don't know what the effect of phenol is on glycoprotein stability of N-linked glycosylation. MR. JAGOE: Q. So you don't know whether or not when someone applies the Miyake method they are actually changing the carbohydrate structure of the carbohydrates on erythropoietin? MS. CARTER: Objection; outside the scope of his expert report, asked and answered. THE WITNESS: I do not have any notion whether phenol changes glyco portions of N-linked carbohydrates on a protein if used in a purification procedure. MR. JAGOE: Q. Prior to 1984, prior to November 30th of 1984, are you aware of any literature references where a protein has been purified on a C4 column using an ethanol gradient? A. I can't cite any personal experience. I never bothered to look in the literature. Whether or not that was done, C4 columns were certainly well known at this time, ethanol gradients were certainly known at this

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of proteins? MS. CARTER: Objection; mischaracterizes his testimony. THE WITNESS: I did not review all the prior art for the Lai patent. But in my experience, the urea, acid urea treatment was unique. I did not do a literature search, but I had never encountered that before. Whereas, I certainly had encountered use of C4 columns. We use C4 columns in my laboratory to purify proteins. Even though we may never have published it, we certainly did. So I was well familiar with C4 columns. I was not familiar with a urea DEAE column, so in my opinion this was a novel step. I wasn't a patent examiner and I didn't look at the prior art. MR. JAGOE: Q. Did you read the discussion of the prior art in the Lai patent before you formed your opinion about its novelty or nonobviousness? A. I read it very briefly, yes. Q. Do you recall anything in there that you disagreed with? MS. CARTER: Objection. I don't think he can answer it without looking at the document. THE WITNESS: I would have to look at the Lai
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pharmaceutical composition? MS. CARTER: Objection; outside the scope of his expert report. MR. JAGOE: Q. In 1985. A. Once again, that requires me to know something about a pharmaceutical composition. If I simply focus on your ability to get urinary EPO, based on the relative scarcity of starting material, the complexity of the Miyake procedure, the statement probably certainly has some validity, to the extent that the statement would have to be analyzed in the context for which it is written. Q. In the 1985 time frame, was it true that there continues to exist a need in the art for rapid and efficient preparatory procedures suitable for recovery of biologically active proteins from recombinant sources? MS. CARTER: Objection; outside the scope of his expert report. THE WITNESS: That's clearly somebody's assessment of a situation. And taken out of context, how could I possibly answer the question? Furthermore, it requires knowledge that I didn't have in 1985, nor do I have now with respect to preparing an economically viable erythropoietin
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patent before answering that question. If you want me to look at the Lai patent, I will be happy to do it. MR. JAGOE: Q. Would you agree with the statement that recovery procedures for erythropoietin from urinary fluid sources have generally been very complex, costly and labor intensive? MS. CARTER: Objection; outside the scope of his expert report, vague as to time. MR. JAGOE: Q. Prior to 1985. MS. CARTER: Incomplete hypothetical, that is taken out of context. THE WITNESS: It is a statement taken out of context. And things like efficiency and so forth all have to do relative to what it is you're trying to accomplish. I would have to know what that statement was in reference to and the context before I could tell whether I agreed with it or not. You've taken it out of context and I have no idea where it came from. MR. JAGOE: Q. But to make a pharmaceutical composition? MS. CARTER: What is the question? MR. JAGOE: Q. The procedures for isolating erythropoietin for urinary fluids is very complex, costly and labor intensive if you want to make it into a

pharmaceutical composition. And so I can't answer that question. MR. JAGOE: Q. Is it fair to say you don't know the state of the art of preparing pure preparations of human erythropoietin as of 1985? MS. CARTER: Objection; mischaracterizes his testimony. THE WITNESS: I have no idea what that question is supposed to mean, so you will have to rephrase it. MR. JAGOE: Q. Do you know what the state of the art was in terms of efforts to purify human erythropoietin from recombinant cells as of 1985? A. My knowledge of this is based on the Lin patents, and I have really no other information as of 1985 for purifying recombinant erythropoietin from anybody else. MR. JAGOE: I will give you a copy of the Lai/Strickland patent. (Exhibit 4 marked for identification.) MR. JAGOE: Q. I would like you to look at Claim 10 of the '016 patent. Is Claim 10 something you are offering opinions about in your declaration that you submitted recently?

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expert reports are, just the two expert reports. (Whereupon, at 5:40 p.m. the deposition of RALPH BRADSHAW, Ph.D. was adjourned.)

I declare under penalty of perjury that the foregoing is true and correct.

Dated:____________________ _________________________ RALPH BRADSHAW, Ph.D.

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STATE OF CALIFORNIA ) ) COUNTY OF ALAMEDA ) I, DIANA NOBRIGA, hereby certify that the witness in the foregoing deposition was by me duly sworn to testify to the truth, the whole truth, and nothing but the truth in the within-entitled cause; that said deposition was taken at the time and place therein stated; that the testimony of said witness was reported by me, a Certified Shorthand Reporter and disinterested person, and was thereafter transcribed into typewriting, and that the pertinent provisions of the applicable code or rules of civil procedure relating to the notification of the witness and counsel for the parties hereto of the availability of the original transcript of the deposition for reading, correcting and signing have been met. And I further certify that I am not of counsel or attorney for either or any of the parties to said deposition, nor in any way interested in the outcome of the cause named in said action. DATED: _____________________ ____________________________ DIANA NOBRIGA, CSR NO. 7071

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