Petition for Inter Partes Review
`of U.S. Patent 9,987,308
`
`U.S. PATENT 9,987,308 CHALLENGED CLAIMS LISTING
`
`Claim
`No.
`
`Limitation
`
`An adoptive cellular immunotherapy composition containing chimeric
`antigen receptor-modified CD4+ T lymphocytes and chimeric antigen
`receptor-modified CD8+ T lymphocytes, wherein:
`(a) the chimeric antigen receptor-modified CD4+ T lymphocytes contain
`a chimeric antigen receptor that specifically binds to an antigen and at
`least 50% of the chimeric antigen receptor-modified CD4+ helper
`T lymphocytes in the composition are surface positive for CD62L and/or
`CD45RA, and
`(b) the chimeric antigen receptor-modified CD8+ T lymphocytes contain
`a chimeric antigen receptor that specifically binds to the antigen and at
`least 50% of CD8+ cytotoxic T lymphocytes in the composition are
`surface positive for CD62L and/or CD45RO.
`
`The adoptive cellular immunotherapy composition according to claim 1,
`wherein the antigen is associated with a disease or disorder selected from
`a solid tumor, hematologic malignancy, melanoma, and infection with a
`pathogen.
`
`The adoptive cellular immunotherapy composition according to claim 1,
`wherein the antigen is selected from ROR1, tEGFR, Her2, L1-CAM,
`CD19, CD20, CD22, mesothelin, and CEA.
`
`The adoptive cellular immunotherapy composition according to claim 1,
`wherein the chimeric antigen receptor of (a) and/or (b) comprises an
`extracellular antibody variable domain or single-chain antibody fragment
`specific for the antigen and an intracellular signaling module.
`
`The adoptive cellular immunotherapy composition according to claim 4,
`wherein each of the intracellular signaling module of the chimeric antigen
`receptor contained by the CD4+ T lymphocytes and the intracellular
`signaling module of the chimeric antigen receptor contained by the CD8+
`T lymphocytes, individually, comprise (a) a CD28 costimulatory domain
`and a CD3 intracellular signaling domain, or (b) a 4-1BB costimulatory
`domain and a CD3 intracellular signaling domain.
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`Miltenyi Ex. 1022 Page 1
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`

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`Claim
`No.
`
`Limitation
`
`Petition for Inter Partes Review
`of U.S. Patent 9,987,308
`
`The adoptive cellular immunotherapy composition according to claim 1,
`wherein:
`(a) at least 60% of the chimeric antigen receptor-modified CD4+
`T lymphocytes are surface positive for CD62L and/or CD45RA;
`(b) at least 60% of the chimeric antigen receptor-modified CD8+
`cytotoxic T lymphocytes are surface positive for CD62L and/or
`CD45RO;
`(c) at least 80% of the chimeric antigen receptor-modified CD4+
`T lymphocytes are surface positive for CD62L and/or CD45RA; and/or
`(d) at least 80% of the chimeric antigen receptor-modified CD8+
`cytotoxic T lymphocytes are surface positive for CD62L and/or
`CD45RO.
`
`The adoptive cellular immunotherapy composition according to claim 1,
`wherein the intracellular signaling domain of the chimeric antigen
`receptor contained by the CD8+ T lymphocytes is the same as the
`intracellular signaling domain of the chimeric antigen receptor contained
`by the CD4+ T lymphocytes.
`
`The adoptive cellular immunotherapy composition according to claim 1,
`wherein the CD4+ helper T lymphocytes and the CD8+ cytotoxic
`T lymphocytes are derived from a subject and wherein the CD4+ helper
`T lymphocytes secrete a greater amount of IL-2 and/or exhibit a greater
`degree of proliferation when cultured in the presence of the antigen as
`compared to a reference population of CD4+ T cells that has been
`expanded in vitro from an effector memory T cell-enriched CD4+ T cell
`population or a bulk CD4+ T cell population from the subject and
`modified to contain the chimeric antigen receptor contained by the CD4+
`helper T lymphocytes.
`
`The adoptive cellular immunotherapy composition of claim 1, wherein at
`least 50% of the chimeric antigen receptor-modified CD4+ helper
`T lymphocytes in the composition are surface positive for CD62L.
`
`The adoptive cellular immunotherapy composition of claim 1, wherein at
`least 50% of the chimeric antigen receptor-modified CD8+ cytotoxic
`T lymphocytes in the composition are surface positive for CD62L.
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`Miltenyi Ex. 1022 Page 2
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`

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`Petition for Inter Partes Review
`of U.S. Patent 9,987,308
`
`Claim
`No.
`
`Limitation
`
`The adoptive cellular immunotherapy composition of claim 1, wherein at
`least 50% of the chimeric antigen receptor-modified CD4+ helper
`T lymphocytes in the composition are surface positive for CD62L and at
`least 50% of the chimeric antigen receptor-modified CD8+ cytotoxic
`T lymphocytes in the composition are surface positive for CD62L.
`
`The adoptive cellular immunotherapy composition of claim 1, wherein at
`least 60% of the chimeric antigen receptor-modified CD4+ helper
`T lymphocytes in the composition are surface positive for CD62L and/or
`at least 60% of the chimeric antigen receptor-modified CD8+ cytotoxic
`T lymphocytes in the composition are surface positive for CD62L.
`
`The adoptive cellular immunotherapy composition of claim 1, wherein at
`least 80% of the chimeric antigen receptor-modified CD4+ helper
`T lymphocytes in the composition are surface positive for CD62L and/or
`at least 80% of the chimeric antigen receptor-modified CD8+ cytotoxic
`T lymphocytes in the composition are surface positive for CD62L.
`
`The adoptive cellular immunotherapy composition of claim 1, wherein
`the chimeric antigen receptor-modified CD4+ helper T lymphocytes in
`the composition and the chimeric antigen receptor-modified CD8+
`cytotoxic T lymphocytes are present in the composition at a ratio of
`between about 2:1 to about 1:2.
`
`The adoptive cellular immunotherapy composition of claim 1, wherein
`the chimeric antigen receptor-modified CD4+ helper T lymphocytes in
`the composition and the chimeric antigen receptor-modified CD8+
`cytotoxic T lymphocytes are present in the composition at a ratio of about
`2:1, 1:1, or 1:2.
`
`The adoptive cellular immunotherapy composition of claim 1, wherein
`the chimeric antigen receptor contained by the CD8+ T lymphocytes is
`the same as the chimeric antigen receptor contained by the CD4+
`T lymphocytes.
`
`The adoptive cellular immunotherapy composition according to claim 1,
`wherein the antigen is ROR1.
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`The adoptive cellular immunotherapy composition according to claim 1,
`wherein the antigen is Her2.
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`Miltenyi Ex. 1022 Page 3
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`Petition for Inter Partes Review
`of U.S. Patent 9,987,308
`
`Claim
`No.
`
`Limitation
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`The adoptive cellular immunotherapy composition according to claim 1,
`wherein the antigen is Ll-CAM.
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`The adoptive cellular immunotherapy composition according to claim 1,
`wherein the antigen is CD19.
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`The adoptive cellular immunotherapy composition according to claim 1,
`wherein the antigen is CD20.
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`The adoptive cellular immunotherapy composition according to claim 1,
`wherein the antigen is CD22.
`
`The adoptive cellular immunotherapy composition according to claim 1,
`wherein the antigen is mesothelin.
`
`The adoptive cellular immunotherapy composition according to claim 1,
`wherein the antigen is CEA.
`
`The adoptive cellular immunotherapy composition according to claim 2,
`wherein the disease or disorder is a solid tumor, hematologic malignancy,
`or melanoma.
`
`The adoptive cellular immunotherapy composition according to claim 2,
`wherein the disease or disorder is a hematologic malignancy.
`
`The adoptive cellular immunotherapy composition according to claim 1,
`wherein the antigen is a tumor associated antigen associated with a cancer
`selected from the group consisting of melanoma, breast cancer, squamous
`cell carcinoma, colon cancer, leukemia, myeloma, prostate cancer, B cell
`lymphoma, breast cancer, prostate cancer, and leukemia.
`
`The adoptive cellular immunotherapy composition according to claim 1,
`wherein a greater percentage of the chimeric antigen receptor-modified
`CD4+ helper T lymphocytes are surface positive for CD62L and/or
`CD45RA as compared to a reference population of CD4+ T cells that has
`been expanded in vitro from an effector memory-enriched CD4+ T cell
`population or a bulk CD4+ T cell population from the subject and
`modified to contain the chimeric antigen receptor contained by the CD4+
`helper T lymphocytes.
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`Miltenyi Ex. 1022 Page 4
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`

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`Petition for Inter Partes Review
`of U.S. Patent 9,987,308
`
`Claim
`No.
`
`Limitation
`
`30
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`31
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`The adoptive cellular immunotherapy composition according to claim 1,
`wherein a greater percentage of the chimeric antigen receptor-modified
`CD8+ cytotoxic T lymphocytes are surface positive for CD62L, CD45RO
`and/or CCR7 as compared to a reference population of CD8+ T cells that
`has been expanded in vitro from an effector memory-enriched CD8+
`T cell population or bulk CD8+ T cell population from the subject and
`modified to contain the chimeric antigen receptor contained by the CD8+
`cytotoxic T lymphocytes.
`
`The adoptive cellular immunotherapy composition according to claim 1,
`the chimeric antigen receptor-modified CD8+ cytotoxic
`wherein
`T lymphocytes proliferate when co-cultured in vitro with the CD4+ helper
`T lymphocytes in the presence of the antigen, to a greater degree as
`compared to the degree of proliferation of the CD8+ cytotoxic
`T lymphocytes when co-cultured, under the same conditions, with a
`reference population of CD4+ T cells expanded in vitro from an effector
`memory-enriched CD4+ T cell population or a bulk CD4+ T cell
`population from the subject and modified to contain the chimeric antigen
`receptor contained by the CD4+ helper T lymphocytes.
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`Miltenyi Ex. 1022 Page 5
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