UNITED STATES PATENT AND TRADEMARK OFFICE
` _______________
` BEFORE THE PATENT TRIAL AND APPEAL BOARD
` _______________
`
`Page 135
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` PHIGENIX, INC.
` Petitioner
` v.
` IMMUNOGEN, INC.
` Patent Owner
` _______________
` Case No. IPR2014-00676
` Patent 8,337,856 B2
` _______________
`
` Volume 2
` DEPOSITION OF MICHAEL G. ROSENBLUM, Ph.D.
` Washington, D.C.
` Wednesday, December 17, 2014
`
`Reported by: John L. Harmonson, RPR
`Job No. 88356
`
`TSG Reporting - Worldwide 877-702-9580
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`IMMUNOGEN 2040, pg. 1
`Phigenix v. Immunogen
`IPR2014-00676
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` _______________
` BEFORE THE PATENT TRIAL AND APPEAL BOARD
` _______________
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`Page 135
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` PHIGENIX, INC.
` Petitioner
` v.
` IMMUNOGEN, INC.
` Patent Owner
` _______________
` Case No. IPR2014-00676
` Patent 8,337,856 B2
` _______________
`
` Volume 2
` DEPOSITION OF MICHAEL G. ROSENBLUM, Ph.D.
` Washington, D.C.
` Wednesday, December 17, 2014
`
`Reported by: John L. Harmonson, RPR
`Job No. 88356
`
`TSG Reporting - Worldwide 877-702-9580
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` December 17, 2014
` 8:32 a.m.
`
` Deposition of MICHAEL G. ROSENBLUM, Ph.D.,
`held at the offices of Andrews Kurth, 1350 I
`Street, N.W., Washington, D.C., pursuant to
`Notice, before John L. Harmonson, a Registered
`Professional Reporter and Notary Public of the
`District of Columbia, who officiated in
`administering the oath to the witness.
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` A P P E A R A N C E S
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`Page 137
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`On Behalf of Petitioner:
` ANDREWS KURTH
` 600 Travis
` Houston, Texas 77002
` BY: GREG PORTER, ESQ.
`
` ANDREWS KURTH
` 1350 I Street, N.W.
` Washington, D.C. 20005
` BY: PING WANG, M.D., ESQ.
`
`On Behalf of Patent Owner:
` STERNE KESSLER GOLDSTEIN & FOX
` 1100 New York Avenue, N.W.
` Washington, D.C. 20005
` BY: ELDORA ELLISON, PH.D., ESQ.
` ERIC STEFFE, ESQ.
`
`ALSO PRESENT:
` JOSEPH J. KENNY, ESQ., ImmunoGen, Inc.
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` M. ROSENBLUM
`--------------------------------------------------
` P R O C E E D I N G S
` 8:32 a.m.
`--------------------------------------------------
` Whereupon,
` MICHAEL G. ROSENBLUM, Ph.D.,
` after having been first duly sworn or affirmed,
` was examined and did testify under oath as
` follows:
` EXAMINATION
` BY MS. ELLISON:
` Q. Good morning, Dr. Rosenblum.
` A. Good morning.
` Q. You understand that you remain under
` oath since yesterday?
` A. I do.
` Q. During any of the breaks since the
` deposition started yesterday morning, have you
` spoken with counsel regarding the substance of
` this case?
` A. I have not.
` Q. Can you tell me how many anti-HER2
` antibodies were known as of March 2000?
` A. No, I cannot.
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` Q. Do you know if it was more than five?
` A. Probably more than five.
` Q. Do you know if it was more than ten?
` A. No, I cannot say for certain how many
`anti-HER2 antibodies there were of different
`species, different subtypes, classes, genetic
`constructs. I cannot say for certain.
` Q. Do you know if there were more than
`ten anti-HER2 antibodies as of March 2000?
` A. I do not know the answer to that.
` Q. I'm going to hand you a copy of
`Exhibit 1006.
` (Exhibit 1006 marked for
` identification and attached hereto.)
`BY MS. ELLISON:
` Q. This is a publication by Sarah
`McKenzie and others published in Oncogene, 1989,
`Volume 4, pages 543 through 548.
` Have you ever read the McKenzie
`publication that's provided as Exhibit 1006?
` A. If you'll just give me a second,
`please.
` I cannot say that I have ever seen
`this publication before.
`
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` Q. Can you tell me how many anti-HER2
`antibodies the McKenzie publication discloses?
`And I'll direct your attention to the abstract as
`well as to Table 1 of the McKenzie publication.
` A. The abstract says a series, so that's
`not a defined number.
` Q. And just to clarify my question, I'm
`asking about antibodies that are specific for
`human HER2.
` I'll withdraw that question for a
`moment and ask you this question, Dr. Rosenblum.
` Isn't it correct that Table 1 of the
`McKenzie reference discloses a number of
`antibodies?
` A. Yes.
` Q. And it discloses a number of anti-p185
`monoclonal antibodies, correct?
` A. Yes.
` Q. And p185 is HER2, correct?
` A. Not necessarily.
` Q. This paper discloses a series of
`monoclonal antibodies specific for the
`extracellular domain of the human neu gene
`protein p185, right? Isn't that when the first
`
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`line of the abstract explains?
` A. The designation p185 has been used
`throughout the literature somewhat from the past
`a bit interchangeably to describe the oncogene
`product from a number of cell lines, mouse, rat
`and human.
` So without further distinction, p185
`as a human neu gene product, it's difficult to
`say which antibodies react with the mouse, which
`antibodies react with the human, and which
`antibodies react with the rat version of that
`particular protein target.
` So your question is a little
`indistinct in terms of what this describes. But
`in answer to your question, the intent of this
`Table 1 intentionally describes a series of
`antibodies which binds to the human HER2/neu gene
`product p185.
` Q. And how many antibodies are disclosed
`in Table 1?
` A. I note that Table 1 lists ten
`different antibody clones designated by different
`letters and numbers. Each purporting to be a
`different antibody.
`
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` Q. Yet each of those antibodies in
`Table 1 -- How many of the antibodies in Table 1
`are purported to bind to human HER2?
` A. Without having read the elements of
`this paper, two of these antibodies are purported
`to bind to HER2 in western blot. Virtually all
`of the antibodies were found to react with HER2
`in an immunoprecipitation. Three of the
`antibodies were found to react in an
`immunofluorescence assay. And seven of the
`antibodies were not tested for
`immunofluorescence. Seven of the antibodies were
`found to -- Excuse me.
` Q. Were you finished with your answer?
` A. I will answer when you're finished --
`I would like to speak to you, and I can't do so
`if you're speaking to a colleague.
` Q. Just answer the question. If you're
`finished with the answer, we can move on to the
`next question.
` A. I'm not finished with my answer.
` Q. Okay. Please finish your answer.
` A. As I was saying, according to Table 1,
`seven of these antibodies appear to react in a
`
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`flow cytometry assay, and three of the antibodies
`were not tested by flow cytometry for binding.
` Q. Can you read into the record the list
`of antibodies disclosed in Table 1?
` A. I can.
` Q. Please do so.
` A. The list of antibodies disclosed in
`Table 1 are BD5, RC1, TA1, NA3, OD3, PB3, RC6,
`NB3, ID5, IB3.
` Q. I'm going to hand you a copy of what
`we've marked as Exhibit 2032.
` (Exhibit 2032 marked for
` identification and attached hereto.)
`BY MS. ELLISON::
` Q. Would you agree with me that
`Exhibit 2032 is a publication by Jeffrey A.
`Drebin and others?
` A. I would.
` Q. And the Drebin publication provided as
`Exhibit 2032 was published in Oncogene, 1988,
`Volume 2, pages 387 to 394, correct?
` A. That is correct.
` Q. Have you ever read the Drebin
`publication that we've provided as Exhibit 2032?
`
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` A. I likely read this manuscript when it
`was published in 1988.
` Q. Have you read it in the last year?
` A. No.
` Q. The Drebin publication discloses
`monoclonal antibodies specific for the neu
`oncogene product, correct?
` A. Well, that's what the title says.
` Q. Do you dispute that that's what it
`discloses?
` A. I haven't read this paper in over 20
`years.
` Q. Do you dispute that that's what the
`paper discloses?
` A. I am simply saying that that is what
`the title says.
` Q. My question is: Do you dispute that
`that's what the paper discloses?
` A. I have not read this paper lately.
` Q. So you have no basis to dispute that
`that's what the paper discloses, correct?
` A. Nor confirm.
` Q. Can you tell me how many anti-HER2
`antibodies are disclosed in the Drebin
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`publication? And I'll direct your attention to
`Figure 1.
` I'll withdraw the previous question.
`I'll ask you this question instead given the time
`it's taken for you to answer the previous
`question.
` Can you tell me how many anti-p185
`antibodies are disclosed in Table 1 of the Drebin
`reference?
` A. My answer is that it's unclear from a
`cursory reading of this publication whether the
`antibodies identified in Figure 1 represent a
`first disclosure of these antibodies or a
`characterization of antibodies previously
`described by the same author, Drebin, et al.,
`1984, or 1986, in which he states in the
`introduction --
` Q. This answer is nonresponsive to the
`question I asked. I asked you first off a
`question about Table 1, not Figure 1. Secondly,
`I simply asked you how many antibodies are
`disclosed in Table 1. I did not ask you whether
`they're previously disclosed. I did not ask you
`about the antibodies in Figure 1 to which your
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`answer was directed.
` So I'm going to ask you really simple
`questions and we will see if you are able to
`answer my really simple questions.
` Does Table 1 disclose an anti-p185
`antibody known as 7.5.5.? Your answer could be
`something like yes, no, I don't know, or some
`other answer that actually answers the question.
` A. I thank you for your guidance. I will
`say that I would appreciate if you would please
`provide a respectful tone for these proceedings,
`as I am trying to do.
` Q. I am trying to get answers to
`questions. That is what the task is here today.
`Your job today is to answer my questions. So if
`you're going to do that, we can continue. If
`you're not going to do that, we can call the
`judge.
` So I'm asking you a really simple
`question. If you need the question read back to
`you, we can have that done.
` A. I am happy to proceed. But it takes
`some time to review a manuscript that I haven't
`seen in a long time. And you're asking fairly
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`complicated questions, and I need to make certain
`that I take the time to give an accurate and
`comprehensive answer.
` Q. So my last question to you is whether
`Table 1 of the Drebin publication discloses an
`anti-p185 antibody known as 7.5.5. Do you find
`that to be a complicated question?
` A. No.
` Q. Okay. Please answer.
` A. I find that Table 1 lists an antibody
`designated 7.5.5 in which it describes the
`anchorage-independent colony formation of this
`particular antibody.
` Q. Does Table 1 disclose an anti-p185
`antibody known as 7.9.5?
` A. I find that Table 1 lists under the
`designation for antibody a 7.9.5 designation that
`describes anchorage-independent colonies
`and percent inhibition of this particular
`antibody.
` Q. Does Table 1 disclose an antibody
`known -- Excuse me. I'll say it again.
` Does Table 1 disclose an anti-p185
`antibody known as 7.16.4?
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` A. Table 1 lists under antibody an
`antibody designated 7.16.4 (anti-p185).
` Q. Does Table 1 disclose an anti-p185
`antibody known as 7.21.2?
` A. Listed under Table 1 under the listing
`for antibodies, there is a listing for a
`designation 7.21.2 in terms of its effects on
`anchorage-independent colony formation.
` Q. I'm going to hand you a new exhibit
`that we've marked as Exhibit 2033.
` (Exhibit 2033 marked for
` identification and attached hereto.)
`BY MS. ELLISON:
` Q. Exhibit 2033 is a publication by Ilana
`Stancovski and others, correct?
` A. Yes.
` Q. And the Stancovski publication was
`published in the proceedings of the National
`Academy of Sciences, Volume 88, pages 8691
`through 8695, in October 1981, correct?
` A. That's what it says.
` Q. Have you ever read the Stancovski
`publication provided as Exhibit 2033?
` A. I'll have to take a moment to look at
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`it.
` The answer is that I may have seen
`this when it was first published.
` Q. Have you read this reference in the
`last year?
` A. No.
` Q. I'm going to direct your attention to
`page 8692 of the Stancovski publication under the
`header in the right-hand column that reads
`"Results." The Stancovski publication states,
`quote: "Generation of mAbs directed to the ErbB2
`receptor."
` Do you see that?
` A. I'm sorry, I'm not sure where you're
`reading.
` Q. Page 8692, right-hand column. See the
`header that says "Results"?
` A. Yes.
` Q. Just below that.
` A. Okay.
` Q. The publication states, "Generation of
`mAbs directed to the ErbB2 receptor."
` Do you see that?
` A. The first sentence is "Five hybridomas
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`were selected." Under "Results."
` Q. Do you see the language that's in bold
`font just before what you just read?
` A. "Generation of mAbs directed at the
`ErbB2 receptor."
` Q. Correct.
` A. Okay.
` Q. And then the paper states, quote:
`"Five hybridomas were selected after the fusion
`of the NSO myeloma cells with splenocytes
`obtained from mice immunized with intact cells of
`the human breast carcinoma SK-BR-3 cell line."
` Do you see that?
` A. I do.
` Q. And isn't it correct that the authors
`reported that this immunization procedure
`elicited specific antibodies to the extracellular
`domain of the human ErbB2 antigen?
` A. That's what that sentence says, yes.
` Q. And isn't it correct that the authors
`also reported that "As depicted in Figure 1" --
`this is a few lines down -- "As depicted in
`Figure 1, all the mAbs specifically bound to
`cultured cells that express the ErbB2 receptor,
`
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`yet they bound with different apparent
`affinities"?
` There is a question pending. If you
`need it read back, we can read it back.
` A. I'm sorry, you were reading this. I
`didn't understand there was a question. Could
`you read the question, please?
` (Whereupon, the requested portion was
` read back by the Reporter.)
`BY MS. ELLISON:
` Q. I'll restate the question to make it a
`little more simple and direct now that I don't
`have to explain where the text is.
` Isn't it correct that the authors also
`reported, quote: "As depicted in Fig. 1, all the
`mAbs specifically bound to cultured cells that
`express the ErbB2 receptor, yet they bound with
`different apparent affinities"?
` A. That's what that sentence says, yes.
` Q. Do you have any basis to dispute the
`results set forth in the Stancovski publication?
` A. Not having read the publication
`recently, I can't say yes or no that that's
`correct.
`
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` Q. Do you have any basis to dispute the
`publication?
` A. No, nor do I have a basis for agreeing
`with the conclusions in the results.
` Q. I'm going to hand you what we've
`marked as Exhibit 2034.
` (Exhibit 2034 marked for
` identification and attached hereto.)
`BY MS. ELLISON:
` Q. Would you agree with me that
`Exhibit 2034 is a publication by Yoshito Kita and
`others?
` A. Yes.
` Q. Would you agree that this paper was
`published in Biochemical and Biophysical Research
`Communications, Volume 226, pages 59 through 69
`in 1996?
` A. Yes, that's what it says.
` Q. Have you ever read the Kita
`publication?
` A. I'll just take a moment to look.
` My answer is that I don't recall
`seeing this particular publication.
` Q. Would you agree with me that the
`
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` M. ROSENBLUM
`abstract of the Kita publication reports that "A
`panel of mAbs were generated against the purified
`soluble form of ErbB2/HER2 receptor,
`corresponding to the extracellular region of the
`receptor, and examined for their ability to mimic
`the receptor ligand"?
` A. That is what the first line of the
`abstract says, the first sentence of the
`abstract.
` Q. I'll direct your attention to page 60
`of the publication under the header that reads
`"Results and Discussion."
` A. Uh-huh.
` Q. Would you agree with me that the
`authors of the Kita publication reported that 12
`clones of the anti-S HER2 mAbs -- I'll start this
`question over again.
` Would you agree with me that the
`authors of the Kita publication reported that 12
`clones of anti-S HER2 mAbs were tested for
`stimulation of receptor tyrosine phosphorylation
`in SK-BR-3 cells?
` A. Yes, the first line of the "Results
`and Discussion" section has that sentence.
`
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` M. ROSENBLUM
` Q. I'll direct your attention to page 68
`of the Kita publication under the header
`"Conclusion." Do you agree with me that the
`authors of the Kita publication reported that
`they have explicitly shown that the mAbs
`generated here against the purified soluble HER2
`corresponding to the extracellular region of the
`receptor are highly specific for HER2, do not
`cross react with the purified soluble HER3 or
`HER4?
` A. I would agree that that is the first
`sentence in the conclusion, but without having
`read this manuscript and considered the data
`herein, I could neither agree or disagree with
`the conclusions that are drawn.
` Q. I'm going to hand you a copy of what
`we've marked as Exhibit 2035.
` (Exhibit 2035 marked for
` identification and attached hereto.)
`BY MS. ELLISON:
` Q. Would you agree with me that
`Exhibit 2035 is a publication by Leah, L-e-a-h,
`Klapper and others?
` A. Yes.
`
`TSG Reporting - Worldwide 877-702-9580
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`IMMUNOGEN 2040, pg. 20
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` M. ROSENBLUM
` Q. And the Klapper publication was
`published in the journal Oncogene in 1997, Volume
`14, pages 2099 through 2109, correct?
` A. That so states.
` Q. Have you ever read the Klapper
`publication that we have provided as
`Exhibit 2035?
` A. I'll have to take a moment and look.
` I don't recall having read this paper
`previously.
` Q. I'll direct your attention to the
`abstract of the Klapper paper, about the middle
`of the abstract. Would you agree that the
`authors of the Klapper publication reported that
`they generated a, quote, "large battery of mAbs
`to ErbB2," close quote?
` A. I agree that that sentence in the
`abstract states that in part.
` Q. I'll direct your attention to
`page 2100, the left-hand column, under the header
`that says "Results." Would you agree that the
`authors reported that essentially mice were
`immunized with a recombinant extracellular domain
`of the human protein and the resulting hybridomas
`
`TSG Reporting - Worldwide 877-702-9580
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`were screened for antibody binding to a cell
`surface expressed ErbB2?
` THE WITNESS: Excuse me. Could you
` read the question back?
` (Whereupon, the requested portion was
` read back by the Reporter.)
` THE WITNESS: I would agree that
` sentence is in the result section.
`BY MS. ELLISON:
` Q. Would you agree that the authors
`reported that they generated a dozen new mAbs
`that bind to ErbB2?
` THE WITNESS: Could you please repeat
` that question?
` (Whereupon, the requested portion was
` read back by the Reporter.)
`BY MS. ELLISON:
` Q. I'll direct your attention --
` A. I don't know. I can't say because I
`haven't -- I'm sorry.
` Q. I was just going to help you out.
`I'll direct your attention to page 2100 in the
`sentence that follows the one that we had just
`read, so this is at the top of the right-hand
`
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`column on page 2100.
` A. Uh-huh. It says: "A dozen new mAbs
`was generated, and analyzed together with a panel
`of five mAbs that we previously described
`(Stancovski et al., 1991)."
` Q. And the authors were referring to mAbs
`the defined erbB2, correct?
` A. I don't know.
` Q. So under the "Results" section, there
`is a header that reads: "Classification of
`anti-erbB2 monoclonal antibodies." Do you see
`that?
` A. I do.
` Q. Do you see where it further reads:
`"Essentially, mice were immunized with a
`recombinant extracellular domain of the human
`protein and the resulting hybridomas were
`screened for antibody binding to a cell
`surface-expressed erbB2. A dozen of new mAbs was
`generated, and analyzed together with a panel of
`five mAbs that we previously described."
` Do you see that?
` A. I do.
` Q. Do you understand those new mAbs to be
`
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`mAbs that bind to erbB2?
` A. I don't know.
` Q. Okay.
` A. It's not clear from what's in here.
`It just says a panel of five mAbs that we
`previously described. And it's impossible to
`know without going to the Stancovski, et al.,
`1991 paper what five mAbs they were talking about
`unless it's further described elsewhere in this
`manuscript. So you're asking me to come to a
`conclusion based on one sentence that is
`indistinct.
` Q. That's not actually what I'm asking
`you. I'm going to ask you another question. I'm
`going to ask you to turn your attention to
`page 2105.
` A. Okay.
` Q. In the right-hand column under the
`header "Discussion," would you agree that the
`authors of the Klapper publication reported: "In
`the present study we used a large collection of
`mAbs to ErbB2" --
` A. I'm sorry, where are you reading?
` Q. I am reading from page 2105, the
`
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` M. ROSENBLUM
`right-hand column, under the header "Discussion."
`It's about six lines down.
` A. I have to apologize, but, you know,
`you didn't tell me where, and I'm trying to look
`through the right-hand column for where you're
`starting.
` So one, two, three, four, five, six --
`Yes.
` Q. Would you agree that the authors of
`the Klapper publication reported that "In the
`present study we used a large collection of mAbs
`to ErbB2, in an attempt to correlate specific
`intrinsic activities of various mAbs with their
`tumor-inhibitory potential"?
` A. I agree that that statement as you
`have read it is in the discussion.
` Q. I'm going to hand you a copy of an
`exhibit that we've marked as Exhibit 2036.
` (Exhibit 2036 marked for
` identification and attached hereto.)
`BY MS. ELLISON:
` Q. Do you agree that Exhibit 2036 is a
`publication by Fengji Xu and others?
` A. Yes.
`
`TSG Reporting - Worldwide 877-702-9580
`
`IMMUNOGEN 2040, pg. 25
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`IPR2014-00676
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` Q. Would you agree that the Xu
`publication was published in the International
`Journal of Cancer, Volume 53, pages 401 through
`408 in 1993?
` A. Yes.
` Q. Have you ever read the Xu publication
`that we have provided as Exhibit 2036?
` A. I'll just have to take a moment and
`look.
` Yes, I've read this paper.
` Q. Have you read it in the last year?
` A. No.
` Q. Approximately when was the last time
`you read the Xu publication?
` A. Probably when it came out.
` Q. So probably in 1993? Is that your
`testimony?
` A. Or thereabouts.
` Q. I'm going to direct your attention to
`the abstract of the Xu publication, about six
`lines down, so the third sentence.
` A. Uh-huh.
` Q. Do you agree that Xu and colleagues
`reported that "To define epitopes of functional
`
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`relevance, 11 monoclonal antibodies (mAbs) were
`evaluated for their ability to bind to the
`extracellular domain of p185"?
` A. That's what that sentence says in the
`abstract.
` Q. Do you have any basis to dispute that
`that's what the authors did?
` A. No.
` Q. Do you know what a humanized antibody
`is?
` A. Yes.
` Q. Can you tell me what a humanized
`antibody is?
` A. In simplest terms, a humanized
`antibody is a human framework that has had
`another species, typically of mouse origin,
`variable domain sequences grafted onto the light
`and heavy chains.
` Q. Do you know what a chimeric antibody
`is?
` A. Yes.
` Q. Can you tell me what a chimeric
`antibody is?
` A. A chimeric antibody is generally, in
`
`TSG Reporting - Worldwide 877-702-9580
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`the literature, referred to as an antibody
`structure in which sections of antibody
`components from one species is grafted into an
`antibody component from another species.
` Q. Are humanized antibodies the same as
`chimeric antibodies?
` A. Humanized antibodies fall under the
`general classification of chimeric antibodies.
` Q. Have you ever made a humanized
`antibody?
` A. Yes.
` Q. You've personally with your own hands
`prepared a humanized antibody?
` A. My lab group under my direction have
`created a humanized antibody.
` Q. Have you ever with your own hands made
`a humanized antibody?
` A. No.
` Q. How many humanized antibodies has your
`laboratory made under your direction?
` A. I would say three or four.
` Q. Would a person of ordinary skill in
`the art have experience in making humanized
`antibodies?
`
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` MR. PORTER: Objection; form.
` THE WITNESS: I'm uncertain as to the
` question. Are you referring to today or are
` you referring to March of 2000?
`BY MS. ELLISON:
` Q. March of 2000.
` A. Thank you for clarifying that.
` MR. PORTER: Objection; form.
`BY MS. ELLISON:
` Q. You understand there is a question
`pending, right?
` A. I do.
` I would say as of March of 2000, a
`person of ordinary skill in the art would have
`limited experience in making humanized
`antibodies.
` Q. And what do you mean by "limited"?
` A. By limited, I mean that there were not
`a whole lot of laboratories outside of select
`commercial groups that were doing this technology
`at the time, March of 2000.
` Q. When you refer to "commercial groups,"
`what groups are you referring to?
` A. The term "commercial group" in this
`
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`case is meant to apply to pharmaceutical
`companies versus academic laboratories.
` Q. Does your term "commercial groups"
`refer to contract research organizations?
` A. In some cases, yes.
` Q. Which contract research organizations
`made humanized antibodies in March of 2000?
` A. I have no idea.
` Q. But you believe they existed; is that
`correct?
` A. Yes.
` Q. Do you know how many existed?
` A. I cannot say.
` Q. Do you know how one makes a humanized
`antibody?
`
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