`______________
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`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`______________
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`MILTENYI BIOMEDICINE GmbH and MILTENYI BIOTEC INC.
`Petitioners,
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`v.
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`THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA
`Patent Owner.
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`_________________________________________________
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`IPR 2022-00853
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`U.S. Patent No. 9,464,140
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`_________________________________________________
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`DECLARATION OF DR. ADAM BAGG
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`UPenn Ex. 2044
`Miltenyi v. UPenn
`IPR2022-00853
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`
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`Case IPR2022-00853
`Patent 9,464,140
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`I, Dr. Adam Bagg, declare as follows:
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`1.
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`I am submitting this declaration to provide information about the
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`drafting of a publication regarding a clinical trial for the therapy now known as
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`Kymriah®. I have reviewed Exhibit 1012, titled “Chimeric Antigen Receptor-
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`Modified T Cells in Chronic Lymphoid Leukemia,” and Exhibit 1013, its
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`accompanying protocol, which I understand the Petitioners collectively refer to as
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`“Porter.” Exhibit 1012 is a copy of that publication and Exhibit 1013 is its
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`supplementary material.
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`2.
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`I have personal knowledge of the facts set forth in this Declaration.
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`All statements made in this Declaration are true to the best of my knowledge.
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`3.
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`If called on to testify, I could and would testify competently as to the
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`topics addressed in this declaration.
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`4.
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`I am currently employed as a Professor of Pathology and Laboratory
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`Medicine at the Hospital of the University of Pennsylvania. I am a
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`hematopathologist and my research interests include the molecular pathology of
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`hematologic neoplasms, including leukemia.
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`5.
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`I am not being compensated for my participation in this case or my
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`time spent preparing this declaration. Other than my employment at the University
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`of Pennsylvania, which commenced in July 1999, and for which I am compensated
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`1
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`UPenn Ex. 2044
`Miltenyi v. UPenn
`IPR2022-00853
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`Case IPR2022-00853
`Patent 9,464,140
`for my role as an employee and not in exchange for my completion of this
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`Declaration, I do not have any financial interest in the outcome of this matter.
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`6.
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`I participated in the research reflected in Porter as a
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`hematopathologist. I am listed in the protocol, Ex. 1013, as a Co-Investigator and
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`as part of the Laboratory Team. I assisted in analyzing samples collected in the
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`course of the patients’ treatment at the request and at the direction of my co-
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`authors. But I did not come up with the idea for the treatment described in Porter.
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`Also, I was not involved in creating the chimeric antigen receptor modified T cells
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`used in the study or in formulating them for administration, nor was I involved in
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`developing the dosing schedules or treatment regimens used in the study or in
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`directing the care for any of the patients in the study.
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`7. More specifically, I have been asked by counsel to describe the extent
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`of my contribution to various portions of Porter and in particular, to the portions
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`that I understand are being cited by the Petitioners in support of their arguments.
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`As set forth in detail below, all of the portions of Porter cited by the Petitioners
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`reflect the work of my co-authors and not me.
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`8.
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`I understand that Petitioners contend that, “Porter reports that a
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`leukemia patient who received autologous T cells transduced with an anti-CD19
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`CAR, i.e., ‘CART19’ cells, was in remission ten months after treatment” and
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`“Porter also discloses that the patient in the clinical trial experienced remission.” I
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`UPenn Ex. 2044
`Miltenyi v. UPenn
`IPR2022-00853
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`
`
`Case IPR2022-00853
`Patent 9,464,140
`did not personally treat the patient. As a laboratory-based hematopathologist, I
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`was responsible for analyzing samples collected for this experimental research
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`patient, at the request and direction of my co-authors. From these analyses, I
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`determined the laboratory result indicating remission and Dr. Porter made the
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`clinical determination of remission, based on the reported results and the patient’s
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`overall clinical/health status.
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`9.
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`I understand that Petitioners contend that, “Porter discloses a
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`pharmaceutical formulation using . . . CAR T cells at a dose of 1.46×105 cells per
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`kg,” that “[t]he patient received a total of 3×108 T cells, of which 5% were
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`transduced,” and that “Porter discloses treating the patient with ‘a total of 1.42×107
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`transduced cells (1.46×105 cells per kilogram).’” I did not contribute to developing
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`the pharmaceutical formulation, the dosage, or the transduction percentage used in
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`this treatment.
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`10.
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`I understand that Petitioners contend that, “Porter discloses
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`transducing its CART-19 construct into T cells derived from a leukemia patient”
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`and “Porter discloses transducing its CART-19 construct with a lentiviral vector
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`comprising a nucleic acid sequence wherein the sequence includes EF-1α
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`promoter.” I did not participate in transducing the CART-19 construct into T cells
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`or designing the vector used to transduce the cells.
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`3
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`UPenn Ex. 2044
`Miltenyi v. UPenn
`IPR2022-00853
`
`
`
`Case IPR2022-00853
`Patent 9,464,140
`I understand that Petitioners contend that, “Porter discloses that the
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`11.
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`infusion bag of CART-19 cells contains ‘the following infusible grade reagents
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`(%v/v): 31.25 plasmalyte-A, 31.25 dextrose (5%), 0.45 NaCl, up to 7.50 DMSO,
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`1.00 dextran 40, 5.00 human serum albumin.’” I did not participate in developing
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`the CART-19 infusion bag or selecting these reagents.
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`12.
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`I understand that Petitioners contend that, “Porter teaches
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`administering a single dose of T cells over three days” with escalating dose
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`percentages, that Porter discloses a dosing regimen “split into three consecutive
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`daily intravenous infusions (10% on day 1, 30% on day 2, and 60% on day 3),” and
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`that “Porter also discloses administering a second dose of T cells on the eleventh
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`day.” I did not participate in developing the dosing regimen for the CART-19
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`cells.
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`13.
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`In short, it was my co-authors, and not me, who developed this study
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`and the idea for this study. They created the CART-19 cells and used them to treat
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`patients in the manner described in Porter. Any descriptions in Porter of the
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`manufacture of CART-19 cells, the pharmaceutical composition used in that study,
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`or the administration to patients of that composition reflects the work of the other
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`authors, and not mine.
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`Miltenyi v. UPenn
`IPR2022-00853
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`Case IPR2022-00853
`Patent 9,464,140
`I declare under penalty of perjury under the laws of the United States
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`14.
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`of America that all statements made herein of my own knowledge are true, and that
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`all statements made on information and belief are believed to be true. I further
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`declare that these statements are made with the full knowledge that willful false
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`statements and the like so made are punishable by fine or imprisonment, or both,
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`under Section 1001 of Title 18 of the United States Code and that such statements
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`may jeopardize the validity of U.S. Patent No. 9,464,140.
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`Executed on ___July 19, 2022___
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`_/Adam Bagg/_______
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`Dr. Adam Bagg
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`UPenn Ex. 2044
`Miltenyi v. UPenn
`IPR2022-00853
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