`
`David L. Cavanaugh
`Reg. No. 36,476
`Owen K. Allen
`Reg. No. 71,118
`Robert J. Gunther, Jr.
`Pro Hac Vice to be filed
`Wilmer Cutler Pickering
`Hale and Dorr LLP
`1875 Pennsylvania Ave., NW
`Washington, DC 20006
`
`Adam R. Brausa
`Reg. No. 60,287
`Daralyn J. Durie
`Pro Hac Vice to be filed
`Durie Tangri LLP
`217 Leidesdorff Street
`San Francisco, CA 94111
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`____________________________________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________________________________________
`
`MYLAN PHARMACEUTICALS, INC.,
`Petitioner,
`
`v.
`
`GENENTECH, INC.,
`Patent Owner.
`____________________________________________
`
`Cases IPR2016-01694
`Patent 6,407,213
`____________________________________________
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`DECLARATION OF JOHN RIDGWAY BRADY
`
`Mylan v. Genentech
`IPR2016-01694
`Genentech Exhibit 2018
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`
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`IPR2016-01694
`Declaration of John Ridgway Brady
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`I, John Ridgway Brady, declare as follows:
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`I.
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`Background
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`1.
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`I am a research technician employed by Genentech, Inc. for the past
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`29 years. During that time, I have performed research in a number of areas
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`including cell culture and cell line development, protein engineering, and bio-
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`oncology.
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`2.
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`In 1984, I obtained my Bachelors of Science degree in cell biology
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`from the University of California, Santa Barbara. In 1987, I began working for
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`Genentech, and I am currently a senior research associate.
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`3.
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`In the late 1980s to early 1990s, I worked in the Cell Genetics
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`Department in the laboratory of Cornelia Gorman, Ph.D., conducting experiments
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`on plasmid construction and expression of proteins in mammalian cell lines.
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`4.
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`During my tenure with Dr. Gorman, I conducted numerous
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`experiments at the direction of Drs. Gorman and Paul Carter to express various
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`humanized 4D5 antibodies in the adenovirus-transformed human embryonic
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`kidney cell line 293.
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`5.
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`In particular, Dr. Carter provided me with vectors containing the DNA
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`encoding for different versions of the humanized 4D5 heavy and light chains, and
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`directed me to produce an assortment of humanized 4D5 antibodies by using
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`combinations of the various heavy and light chains. Per these directions, I
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`expressed and purified different humanized variants of the 4D5 antibody, and then
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`provided them for assay analyses to determine binding affinity to HER2 and an
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`ability to prevent proliferation in the SK-BR-3 cell line. I also developed stable
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`cell lines that expressed certain humanized 4D5 antibodies. This work is included
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`in the research paper, “Humanization of the anti-p185 antibody for human cancer
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`therapy,” published in Proc. Nat’l. Acad. Sci., Vol. 89, pp. 4285-4289, May 1992,
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`which I co-authored.
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`6.
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`The purpose of this work was to develop a humanized 4D5 antibody
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`for use as a human therapeutic to treat cancers overexpressing p185HER2. Our work
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`led to Herceptin®, which is used to treat certain breast and gastric cancers.
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`7.
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`As described below,
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`, I had expressed six humanized
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`4D5 antibodies with different combinations of humanized heavy and light chains
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`and provided them for assay analysis, which showed that each of these variants had
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`binding affinity to HER2.
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`II. My Laboratory Notebooks
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`8.
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`My work on humanized 4D5 antibodies is documented in laboratory
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`notebooks that I maintained. Genentech’s library issued laboratory notebooks to
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`researchers to document their experiments, and each notebook had a unique
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`number.
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`IPR2016-01694
`Declaration of John Ridgway Brady
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`9.
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`Attached to this declaration as Exhibit 2005 is my Notebook 10840,1
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`which Genentech’s library issued to me on
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`. I used Notebook
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`10840 to detail experiments that I conducted from
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` to
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`, relating to the construction of plasmids, and in particular,
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`creating plasmids to express humanized 4D5 antibodies.
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`10. Attached to this declaration as Exhibit 2006 is my Notebook 11162,
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`which was issued to me on
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`. Notebook 11162 details
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`experiments that I conducted from
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`,
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`relating to the transfection of cell lines and assay testing.
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`11. As a Genentech researcher, I am expected to maintain a record of my
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`experiments in my laboratory notebooks. Consistent with this expectation, I
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`recorded the experiments I was doing in real time, providing the date of the
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`experiment at the top left-hand corner of the page, followed by a brief description
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`of the protocol and results. After an experiment was completed, I further dated and
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`signed the page in the lower right-hand corner, and obtained the signature of a
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`1
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`Notebooks 10840 and 11162 were issued under the name John Ridgway,
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`which was my legal name at the time. In 1996, I changed my legal name from
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`John Ridgway to John Ridgway Brady.
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`witness. As a result, the date in the upper left-hand corner of each page is the date
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`that I performed the experiment recorded on the page.
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`12.
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`I kept my laboratory notebooks in the ordinary course of my work as a
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`research technician with Genentech. I have retained my laboratory notebooks in
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`my possession in connection with my work at Genentech, except to allow for
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`filming and/or scanning by Genentech’s records department. Genentech regularly
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`creates copies of completed notebooks as an additional record of each researcher’s
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`work. For example, as shown on the covers of my Notebooks 10840 and 11162,
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`they were both originally filmed on December 23, 1991.
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`III. My Work on Humanized 4D5 Antibodies
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`13.
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`21.
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`22.
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`24.
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`IPR2016-01694
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`I declare under penalty of perjury of the laws of the United States of
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`America that the foregoing is true and correct.
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`Date: December 5, 2016
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