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    PROPROTEINS AND METHODS OF USE THEREOF
    1.
    发明申请
    PROPROTEINS AND METHODS OF USE THEREOF 审中-公开
    优点及其使用方法

    公开(公告)号：WO2010096838A3

    公开(公告)日：2014-04-03

    申请号：PCT/US2010025121

    申请日：2010-02-23

    Applicant: CYTOMX THERAPEUTICS INC ,  STAGLIANO NANCY E ,  WEST JAMES W ,  KAMATH KATHRYN ,  BESSETTE PAUL H ,  SAGERT JASON

    Inventor： STAGLIANO NANCY E ,  WEST JAMES W ,  KAMATH KATHRYN ,  BESSETTE PAUL H ,  SAGERT JASON

    IPC: A01N37/18 ,  A61K38/10

    CPC classification number: C07K14/56 ,  A61K38/00 ,  A61K47/48246 ,  A61K47/48338 ,  A61K47/64 ,  A61K47/65 ,  C07K14/00 ,  C07K14/555 ,  C07K14/565 ,  C07K14/57 ,  C07K14/705 ,  C07K16/00 ,  C07K19/00 ,  C07K2319/10 ,  C07K2319/31 ,  C07K2319/33 ,  C07K2319/50 ,  C07K2319/70 ,  C07K2319/90 ,  C12N15/1037 ,  G01N33/6866

    Abstract: The present disclosure provides for proprotein and activatable proprotein compositions. A proprotein contains a functional protein (i.e. a full length protein or functional fragment thereof) which is coupled to a peptide mask that inhibits the binding of the functional protein to its target or binding partner. An activatable proprotein contains a functional protein coupled to a peptide mask, and further coupled to an activatable linker, wherein in an non-activated state, the peptide mask inhibits binding of the functional protein to its target or binding partner and in an activated state the peptide mask does not inhibit binding of the functional protein to its target or binding partner. Proproteins can provide for reduced toxicity and adverse side effects that could otherwise result from binding of a functional protein at non-treatment sites if it were not inhibited from binding its binding partner. Proproteins can further provide improved biodistribution characteristics. Proproteins containing a peptide mask can display a longer in vivo or serum half-life than the corresponding functional protein not containing a peptide mask. The disclosure further provides methods of screening for, making, and using these proproteins.

    Abstract translation: 本公开内容提供了蛋白质和可激活的前蛋白组合物。 前蛋白含有功能蛋白（即其全长蛋白质或其功能片段），其与抑制功能蛋白与其靶标或结合配偶体的结合的肽掩模偶联。 可激活的蛋白质包含与肽掩模偶联的功能性蛋白质，并进一步与可活化接头偶联，其中在非活化状态下，肽掩模抑制功能性蛋白质与其靶标或结合配偶体的结合，并且在活化状态下 肽掩模不抑制功能蛋白与其靶或结合配偶体的结合。 前体蛋白可以提供如果不抑制结合其结合配偶体的功能性蛋白质在非处理部位的结合，则可以提供降低的毒性和不良副作用。 前体蛋白可进一步提供改善的生物分布特征。 含有肽掩模的前体蛋白可以显示比不含肽掩模的相应功能蛋白质更长的体内或血清半衰期。 本公开进一步提供筛选，制备和使用这些蛋白质的方法。

    INTEGRATED FLUIDIC DEVICES WITH MAGNETIC SORTING
    2.
    发明申请
    INTEGRATED FLUIDIC DEVICES WITH MAGNETIC SORTING 审中-公开
    具有磁性分离的集成流体装置

    公开(公告)号：WO2008147530A1

    公开(公告)日：2008-12-04

    申请号：PCT/US2008006599

    申请日：2008-05-23

    Applicant: UNIV CALIFORNIA ,  CYTOMX LLC ,  SOH HYONGSOK ,  FERGUSON BRIAN SCOTT ,  ZHANG YANTING ,  STAGLIANO NANCY E

    Inventor： SOH HYONGSOK ,  FERGUSON BRIAN SCOTT ,  ZHANG YANTING ,  STAGLIANO NANCY E

    IPC: B03C1/00

    CPC classification number: B03C1/015 ,  B01L3/502761 ,  B01L2200/0636 ,  B01L2200/0668 ,  B03C1/286 ,  B03C1/288 ,  B03C5/028 ,  B03C2201/18 ,  B03C2201/26

    Abstract: A fluidic device employs one or more sorting stations for separating target species from other species in a sample. At least one of the sorting stations employs a magnetic field gradient to accomplish separation. In addition, the sorting station is integrated on a single substrate with one or more other modules for processing the sample. For example, the fluidic device may include both a sorting station and a separate trapping station that holds some or all components of the sample for additional processing. The trapping station may be located at a position upstream or downstream from the sorting module.

    Abstract translation: 流体装置采用一个或多个分选站，用于将样品中的目标物种与其他物种分离。 至少一个分选站采用磁场梯度来实现分离。 此外，分选站集成在具有用于处理样品的一个或多个其他模块的单个基板上。 例如，流体装置可以包括分选站和分离收集站，分离站收集样品的一些或所有组分以用于附加处理。 捕集站可以位于分拣模块上游或下游的位置。

    METHODS AND COMPOSITIONS FOR TREATING CARDIOVASCULAR DISEASE USING 1722, 10280, 59917, 85553, 10653, 9235, 21668, 17794, 2210, 6169, 10102, 21061,17662,1468,12282, 6350, 9035,1820, 23652, 7301, 8925, 8701, 3533, 9462, 9123,12788,17729, 65552,1261, 21476, 33770, 9380, 2569654, 33556, 53656, 44143, 32612, 10671, 261, 44570, 4
    4.
    发明申请
    METHODS AND COMPOSITIONS FOR TREATING CARDIOVASCULAR DISEASE USING 1722, 10280, 59917, 85553, 10653, 9235, 21668, 17794, 2210, 6169, 10102, 21061,17662,1468,12282, 6350, 9035,1820, 23652, 7301, 8925, 8701, 3533, 9462, 9123,12788,17729, 65552,1261, 21476, 33770, 9380, 2569654, 33556, 53656, 44143, 32612, 10671, 261, 44570, 4 审中-公开
    用于治疗心血管疾病的方法和组合物，使用1722,10280,59917,85553,1063,5225,26668,17794,2210,6149,10102,21061,17662,1468,12282,63050,17535,1820,236522,7301,8925， 8701,3533,9462,9123,12788,17729,65552,1261,21476,33770,9380,2569654,33556,5366,44143,32612,10671,261,4457,4

    公开(公告)号：WO2004063340A3

    公开(公告)日：2005-07-14

    申请号：PCT/US2004000393

    申请日：2004-01-13

    Applicant: MILLENNIUM PHARM INC ,  STAGLIANO NANCY E ,  HEALY AILEEN ,  ACTON SUSAN L ,  GALVIN KATHERINE M ,  DONOGHUE MARY A ,  ROGRIGUE-WAY AMELIE ,  TOMLINSON JAMES E

    Inventor： STAGLIANO NANCY E ,  HEALY AILEEN ,  ACTON SUSAN L ,  GALVIN KATHERINE M ,  DONOGHUE MARY A ,  ROGRIGUE-WAY AMELIE ,  TOMLINSON JAMES E

    IPC: C07K14/47 ,  G01N33/53 ,  A61K38/00 ,  C07K14/00

    CPC classification number: C07K14/47

    Abstract: The present invention relates to methods for the diagnosis and treatment of cardiovascular disease, including, but not limited to, atherosclerosis, reperfusion injury, hypertension, restenosis, arterial inflammation, thrombosis and endothelial cell disorders. Specifically, the present invention identifies the differential expression of 1722, 10280, 59917, 85553, 10653, 9235, 21668, 17794, 2210, 6169, 10102, 21061, 17662, 1468, 12282, 6350, 9035, 1820, 23652, 7301, 8925, 8701, 3533, 9462, 9123, 12788, 17729, 65552, 1261, 21476, 33770, 9380, 2569654, 33556, 53656, 44143, 32612, 10671, 261, 44570, 41922, 2552, 2417, 19319, 43969, 8921, 8993, 955, 32345, 966, 1920, 17318, 1510, 14180, 26005, 554, 16408, 42028, 112091, 13886, 13942, 1673, 54946 and 2419 genes in cardiovascular disease states, relative to their expression in normal, or non­cardiovascular disease states, and/or in response to manipulations relevant to cardiovascular disease. The present invention describes methods for the diagnostic evaluation and prognosis of various cardiovascular diseases, and for the identification of subjects exhibiting a predisposition to such conditions. The invention also provides methods for identifying a compound capable of modulating cardiovascular disease. The present invention also provides methods for the identification and therapeutic use of compounds as treatments of cardiovascular disease.

    Abstract translation: 本发明涉及用于诊断和治疗心血管疾病的方法，包括但不限于动脉粥样硬化，再灌注损伤，高血压，再狭窄，动脉炎症，血栓形成和内皮细胞疾病。 具体地说，本发明鉴定了1722,1028,8059917,85553,1063,53235,26668,17794,2210,6169,1010,21061,17662,1468,12282,65050,9035,1820,236522,7301,6005的标准差， 8925,8701,33533,9462,9123,12788,17729,65552,1261,21476,33770,9380,2569654,33556,5366,44143,32612,10677,261,44570,41922,2552,2417,19319,4399， 8921,8993,905,232345,996,1920,17318,1510,14180,26205,554,16408,42028,112091,13886,13942,1673,5496和2419中的基因，相对于它们在正常的表达，心血管疾病状态， 或非心血管疾病状态，和/或响应与心血管疾病相关的操作。 本发明描述了各种心血管疾病的诊断评估和预后的方法，以及用于鉴定表现出这种病症倾向的受试者。 本发明还提供了鉴定能调节心血管疾病的化合物的方法。 本发明还提供了用于鉴定和治疗化合物作为心血管疾病治疗的方法。

    PROPROTEINS AND METHODS OF USE THEREOF
    5.
    发明申请
    PROPROTEINS AND METHODS OF USE THEREOF 审中-公开
    优点及其使用方法

    公开(公告)号：WO2010096838A2

    公开(公告)日：2010-08-26

    申请号：PCT/US2010/025121

    申请日：2010-02-23

    Applicant: CYTOMX THERAPEUTICS, LLC ,  STAGLIANO, Nancy, E. ,  WEST, James, W. ,  KAMATH, Kathryn ,  BESSETTE, Paul, H. ,  SAGERT, Jason

    Inventor： STAGLIANO, Nancy, E. ,  WEST, James, W. ,  KAMATH, Kathryn ,  BESSETTE, Paul, H. ,  SAGERT, Jason

    IPC: A61K38/21 ,  C07K14/00 ,  C07K14/555 ,  C07K16/00 ,  A61K38/16 ,  A61K39/395 ,  A61P35/04

    CPC classification number: C07K14/56 ,  A61K38/00 ,  A61K47/64 ,  A61K47/65 ,  C07K14/00 ,  C07K14/555 ,  C07K14/565 ,  C07K14/57 ,  C07K14/705 ,  C07K16/00 ,  C07K19/00 ,  C07K2319/10 ,  C07K2319/31 ,  C07K2319/33 ,  C07K2319/50 ,  C07K2319/70 ,  C07K2319/90 ,  C12N15/1037 ,  G01N33/6866

    Abstract: The present disclosure provides for proprotein and activatable proprotein compositions. A proprotein contains a functional protein (i.e. a full length protein or functional fragment thereof) which is coupled to a peptide mask that inhibits the binding of the functional protein to its target or binding partner. An activatable proprotein contains a functional protein coupled to a peptide mask, and further coupled to an activatable linker, wherein in an non-activated state, the peptide mask inhibits binding of the functional protein to its target or binding partner and in an activated state the peptide mask does not inhibit binding of the functional protein to its target or binding partner. Proproteins can provide for reduced toxicity and adverse side effects that could otherwise result from binding of a functional protein at non-treatment sites if it were not inhibited from binding its binding partner. Proproteins can further provide improved biodistribution characteristics. Proproteins containing a peptide mask can display a longer in vivo or serum half-life than the corresponding functional protein not containing a peptide mask. The disclosure further provides methods of screening for, making, and using these proproteins.

    Abstract translation: 本公开内容提供了蛋白质和可激活的前蛋白组合物。 前蛋白含有功能蛋白（即其全长蛋白质或其功能片段），其与抑制功能蛋白与其靶标或结合配偶体的结合的肽掩模偶联。 可激活的蛋白质包含与肽掩模偶联的功能性蛋白质，并进一步与可活化接头偶联，其中在非活化状态下，肽掩模抑制功能性蛋白质与其靶标或结合配偶体的结合，并且在活化状态下 肽掩模不抑制功能蛋白与其靶或结合配偶体的结合。 前体蛋白可以提供如果不抑制结合其结合配偶体的功能性蛋白质在非处理部位的结合，则可以提供降低的毒性和不良副作用。 前体蛋白可进一步提供改善的生物分布特征。 含有肽掩模的前体蛋白可以显示比不含肽掩模的相应功能蛋白更长的体内或血清半衰期。 本公开进一步提供筛选，制备和使用这些蛋白质的方法。

    ACTIVATABLE BINDING POLYPEPTIDES AND METHODS OF IDENTIFICATION AND USE THEREOF
    7.
    发明申请
    ACTIVATABLE BINDING POLYPEPTIDES AND METHODS OF IDENTIFICATION AND USE THEREOF 审中-公开
    活化结合多肽及其鉴定和使用方法

    公开(公告)号：WO2009025846A3

    公开(公告)日：2009-05-14

    申请号：PCT/US2008009974

    申请日：2008-08-21

    Applicant: UNIV CALIFORNIA ,  CYTOMX LLC ,  DAUGHERTY PATRICK SEAN ,  STAGLIANO NANCY E ,  THOMAS JERRY ,  KAMATH KATHRYN ,  WEST JAMES W ,  KHARE SANJAY

    Inventor： DAUGHERTY PATRICK SEAN ,  STAGLIANO NANCY E ,  THOMAS JERRY ,  KAMATH KATHRYN ,  WEST JAMES W ,  KHARE SANJAY

    IPC: C07K14/00 ,  A61K39/395

    CPC classification number: C07K16/22 ,  C07K16/24 ,  C07K16/2818 ,  C07K16/2836 ,  C07K16/42 ,  C07K2317/34 ,  C07K2317/622 ,  C07K2319/00 ,  C07K2319/30 ,  C07K2319/50 ,  C12N15/1034 ,  C12N15/1044

    Abstract: The present disclosure provides activatable binding polypeptides (ABPs), which contain a target binding moiety (TBM), a masking moiety (MM), and a cleavable moiety (CM). The present disclosure provides activatable antibody compositions, which contain a TBM containing an antigen binding domain (ABD), a MM and a CM. Furthermore the present disclosure also provides ABPs which contain a first TBM, a second TBM and a CM. The ABPs exhibit an "activatable" conformation such that at least one of the TBMs is less accessible to target when uncleaved than after cleavage of the CM in the presence of a cleaving agent capable of cleaving the CM. The disclosure further provides libraries of candidate ABPs, methods of screening to identify such ABPs, and methods of use. The disclosure further provides ABPs having TBMs that bind VEGF, CTLA-4, or VCAM, ABPs having a first TBM that binds VEGF and a second TBM that binds FGF, as well as compositions and methods of use.

    Abstract translation: 本公开提供了包含靶结合部分（TBM），掩蔽部分（MM）和可切割部分（CM）的可活化结合多肽（ABP）。 本公开内容提供了可激活的抗体组合物，其含有含有抗原结合结构域（ABD），MM和CM的TBM。 此外，本公开还提供了包含第一TBM，第二TBM和CM的ABP。 ABP表现出“可活化”构象，使得在未切割时至少一个TBM对靶的接近性低于在能够切割CM的切割剂存在下切割CM后。 本公开还提供了候选ABP的文库，筛选以鉴定这些ABP的方法，以及使用方法。 本公开还提供了具有结合VEGF，CTLA-4或VCAM的TBM的ABP，具有结合VEGF的第一TBM和结合FGF的第二TBM的ABP，以及组合物和使用方法。

    METHODS AND COMPOSITIONS FOR TREATING CARDIOVASCULAR DISEASE USING 1722, 10280, 59917, 85553, 10653, 9235, 21668, 17794, 2210, 6169, 10102, 21061,17662,1468,12282, 6350, 9035,1820, 23652, 7301, 8925, 8701, 3533, 9462, 9123,12788,17729, 65552,1261, 21476, 33770, 9380, 2569654, 33556, 53656, 44143, 32612, 10671, 261, 44570, 4
    10.
    发明申请
    METHODS AND COMPOSITIONS FOR TREATING CARDIOVASCULAR DISEASE USING 1722, 10280, 59917, 85553, 10653, 9235, 21668, 17794, 2210, 6169, 10102, 21061,17662,1468,12282, 6350, 9035,1820, 23652, 7301, 8925, 8701, 3533, 9462, 9123,12788,17729, 65552,1261, 21476, 33770, 9380, 2569654, 33556, 53656, 44143, 32612, 10671, 261, 44570, 4 审中-公开
    用于治疗心血管疾病的方法和组合物，使用1722,10280,59917,85553,1063,5225,26668,17794,2210,6149,10102,21061,17662,1468,12282,63050,17535,1820,236522,7301,8925， 8701,3533,9462,9123,12788,17729,65552,1261,21476,33770,9380,2569654,33556,5366,44143,32612,10671,261,4457,4

    公开(公告)号：WO2004063340A2

    公开(公告)日：2004-07-29

    申请号：PCT/US2004/000393

    申请日：2004-01-13

    Applicant: MILLENNIUM PHARMACEUTICALS, INC. ,  STAGLIANO, Nancy, E. ,  HEALY, Aileen ,  ACTON, Susan, L. ,  GALVIN, Katherine, M. ,  DONOGHUE, Mary, A. ,  ROGRIGUE-WAY, Amelie ,  TOMLINSON, James, E.

    Inventor： STAGLIANO, Nancy, E. ,  HEALY, Aileen ,  ACTON, Susan, L. ,  GALVIN, Katherine, M. ,  DONOGHUE, Mary, A. ,  ROGRIGUE-WAY, Amelie ,  TOMLINSON, James, E.

    IPC: C12N

    CPC classification number: C07K14/47

    Abstract: The present invention relates to methods for the diagnosis and treatment of cardiovascular disease, including, but not limited to, atherosclerosis, reperfusion injury, hypertension, restenosis, arterial inflammation, thrombosis and endothelial cell disorders. Specifically, the present invention identifies the differential expression of 1722, 10280, 59917, 85553, 10653, 9235, 21668, 17794, 2210, 6169, 10102, 21061, 17662, 1468, 12282, 6350, 9035, 1820, 23652, 7301, 8925, 8701, 3533, 9462, 9123, 12788, 17729, 65552, 1261, 21476, 33770, 9380, 2569654, 33556, 53656, 44143, 32612, 10671, 261, 44570, 41922, 2552, 2417, 19319, 43969, 8921, 8993, 955, 32345, 966, 1920, 17318, 1510, 14180, 26005, 554, 16408, 42028, 112091, 13886, 13942, 1673, 54946 and 2419 genes in cardiovascular disease states, relative to their expression in normal, or non­cardiovascular disease states, and/or in response to manipulations relevant to cardiovascular disease. The present invention describes methods for the diagnostic evaluation and prognosis of various cardiovascular diseases, and for the identification of subjects exhibiting a predisposition to such conditions. The invention also provides methods for identifying a compound capable of modulating cardiovascular disease. The present invention also provides methods for the identification and therapeutic use of compounds as treatments of cardiovascular disease.

    Abstract translation: 本发明涉及用于诊断和治疗心血管疾病的方法，包括但不限于动脉粥样硬化，再灌注损伤，高血压，再狭窄，动脉炎症，血栓形成和内皮细胞疾病。 具体地说，本发明鉴定了1722,1028,8059917,85553,1063,53235,26668,17794,2210,6169,1010,21061,17662,1468,12282,65050,9035,1820,236522,7301,6005的标准差， 8925,8701,33533,9462,9123,12788,17729,65552,1261,21476,33770,9380,2569654,33556,5366,44143,32612,10677,261,44570,41922,2552,2417,19319,4399， 8921,8993,905,232345,996,1920,17318,1510,14180,26205,554,16408,42028,112091,13886,13942,1673,5496和2419中的基因，相对于它们在正常的表达，心血管疾病状态， 或非心血管疾病状态，和/或响应与心血管疾病相关的操作。 本发明描述了各种心血管疾病的诊断评估和预后的方法，以及用于鉴定表现出这种病症倾向的受试者。 本发明还提供了鉴定能调节心血管疾病的化合物的方法。 本发明还提供了用于鉴定和治疗化合物作为心血管疾病治疗的方法。

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