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    Method of preparing a modified granulocyte colony stimulating factor (G-CSF) with reduced immunogenicity
    1.
    发明授权
    Method of preparing a modified granulocyte colony stimulating factor (G-CSF) with reduced immunogenicity 失效
    制备具有降低免疫原性的改良粒细胞集落刺激因子（G-CSF）的方法

    公开(公告)号：US07392141B2

    公开(公告)日：2008-06-24

    申请号：US10467396

    申请日：2002-02-05

    申请人： Francis J. Carr ,  Graham Carter ,  Tim Jones ,  Stephen Williams

    发明人： Francis J. Carr ,  Graham Carter ,  Tim Jones ,  Stephen Williams

    IPC分类号： G06F19/00 ,  G06F17/00 ,  G06G7/58 ,  C12P21/06 ,  G01N33/53 ,  G01N33/00 ,  A61K39/00

    CPC分类号： C07K14/535 ,  A61K9/7015 ,  A61K38/00 ,  A61K47/02 ,  A61K47/12 ,  C07K14/54 ,  C07K16/18 ,  C07K16/2866 ,  C07K16/2896 ,  C07K16/30 ,  C07K16/3046 ,  C07K16/464 ,  C07K2319/00 ,  G06F19/16 ,  G06F19/18 ,  Y10S707/99943

    摘要： A method of preparing a modified granulocyte colony stimulating factor (G-CSF) protein having reduced immunogenicity relative to human G-CSF comprises the steps of (i) identifying one or more potential T-cell epitopes within the amino acid sequence of human G-CSF (SEQ ID NO: 1); (ii) designing at least one sequence variant of at least one potential T-cell epitope identified in step (i), wherein the sequence variant eliminates or substantially reduces the MHC class II binding activity of the potential T-cell epitope; (iii) preparing, by recombinant DNA techniques, at least one modified G-CSF protein including a sequence variant designed in step (ii); (iv) evaluating at least one modified G-CSF protein prepared in step (iii) for G-CSF activity and immunogenicity; and (v) selecting a modified G-CSF protein evaluated in step (iv) that has substantially the same therapeutic G-CSF biological activity as, but substantially less immunogenicity than, human G-CSF.

    摘要翻译： 制备相对于人G-CSF具有降低的免疫原性的修饰的粒细胞集落刺激因子（G-CSF）蛋白质的方法包括以下步骤：（i）鉴定人G-蛋白的氨基酸序列内的一个或多个潜在T细胞表位， CSF（SEQ ID NO：1）; （ii）设计步骤（i）中鉴定的至少一个潜在T细胞表位的至少一个序列变体，其中所述序列变体消除或显着降低潜在T细胞表位的MHC II类结合活性; （iii）通过重组DNA技术制备至少一种修饰的G-CSF蛋白，包括在步骤（ii）中设计的序列变体; （iv）评估在步骤（iii）中制备的至少一种修饰的G-CSF蛋白质的G-CSF活性和免疫原性; 和（v）选择在步骤（iv）中评估的与人G-CSF具有基本上相同的治疗性G-CSF生物学活性但显着更低的免疫原性的修饰的G-CSF蛋白质。

    Modified interferon beta with reduced immunogenicity
    4.
    发明授权
    Modified interferon beta with reduced immunogenicity 有权
    修饰的干扰素β具有降低的免疫原性

    公开(公告)号：US07381795B2

    公开(公告)日：2008-06-03

    申请号：US10471894

    申请日：2002-03-15

    申请人： Francis J. Carr ,  Graham Carter ,  Tim Jones ,  John Watkins ,  Matthew Baker

    发明人： Francis J. Carr ,  Graham Carter ,  Tim Jones ,  John Watkins ,  Matthew Baker

    IPC分类号： C07K14/00 ,  C12N15/24

    CPC分类号： C07K14/565

    摘要： A modified interferon beta (INFβ) is provided, which is less immunogenic than human INFβ (SEQ ID NO: 1) when administered to a human in vivo. The modified INFβ comprises an amino acid residue sequence that differs from SEQ ID NO: 1 by a substitution at one or more residues of SEQ ID NO: 1. Preferred substitutions are at residues selected from the group consisting of residue 50, 59, 60, 62, 63, 66, 67, 69, 70, 125, 126, 129, 130, 132, 133, and 138. Examples of suitable substitutions include F50A, L57A, I59A, Y60N, M62A, L63A, I66T, F67H, I69A, F70A, Y125A, Y126A, I129A, L130A, Y132S, L133A, Y138H, and Y138A.

    摘要翻译： 提供了经修饰的干扰素β（INFbeta），当其在体内施用于人时，其比人INFbeta（SEQ ID NO：1）的免疫原性较低。 修饰的INFbeta包含通过在SEQ ID NO：1的一个或多个残基处的取代而与SEQ ID NO：1不同的氨基酸残基序列。优选的取代是选自残基50,59,60， 合适的取代的实例包括F50A，L57A，I59A，Y60N，M62A，L63A，I66T，F67H，I69A，SEQ ID NO：6,62,63,66,67,69,70,125,126,129,130​​,132,133,138。 F70A，Y125A，Y126A，I129A，L130A，Y132S，L133A，Y138H和Y138A。

    Modified interferon beta with reduced immunogenicity
    6.
    发明授权
    Modified interferon beta with reduced immunogenicity 失效
    修饰的干扰素β具有降低的免疫原性

    公开(公告)号：US07615615B2

    公开(公告)日：2009-11-10

    申请号：US12077120

    申请日：2008-03-17

    申请人： Francis J. Carr ,  Graham Carter ,  Tim Jones ,  John Watkins ,  Matthew Baker

    发明人： Francis J. Carr ,  Graham Carter ,  Tim Jones ,  John Watkins ,  Matthew Baker

    IPC分类号： C07K14/00 ,  A61K38/19 ,  C12N15/24

    CPC分类号： C07K14/565

    摘要： The present invention relates a modified human interferon beta (INFβ) which is less immunogenic than human INFβ (SEQ ID NO: 1) when administered in vivo to a human. The modified human INFβ comprises an amino acid residue sequence that differs from SEQ ID NO: 1 by an amino acid residue substitution selected from the group consisting of L57A, L57C, L57D L57E, L57G, L57H, L57K, L57N, L57P, L57Q, L57R, L57S, and L57T and an additional substitution selected from the group consisting of the H140A, H140C, H140G, and H140P.

    摘要翻译： 本发明涉及当在体内施用于人时，比人INFbeta（SEQ ID NO：1）具有较少的免疫原性的修饰的人干扰素β（INFbeta）。 修饰的人INFbeta包含与SEQ ID NO：1不同的氨基酸残基，其选自L57A，L57C，L57D，L57E，L57G，L57H，L57K，L57N，L57P，L57Q，L57R ，L57S和L57T以及选自H140A，H140C，H140G和H140P的另外的取代基。

    Modified interferon beta with reduced immunogenicity
    7.
    发明申请
    Modified interferon beta with reduced immunogenicity 有权
    修饰的干扰素β具有降低的免疫原性

    公开(公告)号：US20050054052A1

    公开(公告)日：2005-03-10

    申请号：US10471894

    申请日：2002-03-15

    申请人： Francis Carr ,  Graham Carter ,  Tim Jones ,  John Watkins

    发明人： Francis Carr ,  Graham Carter ,  Tim Jones ,  John Watkins

    IPC分类号： C12N15/09 ,  A61K38/21 ,  A61K39/00 ,  A61P31/12 ,  A61P37/02 ,  C07K7/08 ,  C07K14/565 ,  C12N15/22 ,  C12P21/02 ,  C07H21/04 ,  C07K14/765 ,  C12P21/04

    CPC分类号： C07K14/565

    摘要： The present invention relates to polypeptides to be administered especially to humans and in particular for therapeutic use. The polypeptides are modified polypeptides whereby the modification results in a reduced propensity for the polypeptide to elicit an immune response upon administration to the human subject. The invention in particular relates to the modification of human interferon beta to result in proteins that are substantially non-immunogenic or less immunogenic than any non-modified counterpart when used in vivo.

    摘要翻译： 本发明涉及特别用于人，特别是用于治疗用途的多肽。 所述多肽是修饰的多肽，其中所述修饰导致多肽在施用于人受试者时引起免疫应答的倾向降低。 本发明特别涉及人类干扰素β的修饰，以产生当在体内使用时与任何未修饰的对应物基本上不具有免疫原性或较低免疫原性的蛋白质。

    Modified interferon alpha with reduced immunogenicity
    8.
    发明申请
    Modified interferon alpha with reduced immunogenicity 审中-公开
    修饰的干扰素α具有降低的免疫原性

    公开(公告)号：US20060062761A1

    公开(公告)日：2006-03-23

    申请号：US10469679

    申请日：2002-03-01

    申请人： Francis Carr ,  Graham Carter ,  Tim Jones ,  Matthew Baker ,  John Watkins ,  Marian Hanlon

    发明人： Francis Carr ,  Graham Carter ,  Tim Jones ,  Matthew Baker ,  John Watkins ,  Marian Hanlon

    IPC分类号： C07K14/56 ,  C07H21/04 ,  C12P21/04 ,  A61K38/21

    CPC分类号： C07K7/06 ,  A61K38/00 ,  C07K14/56

    摘要： The present invention relates to polypeptides to be administered especially to humans and in particular for therapeutic use. The polypeptides are modified polypeptides whereby the modification results in a reduced propensity for the polypeptide to elicit an immune response upon administration to the human subject. The invention in particular to the modification of human interferon alpha and specifically interferon alpha 2(INFα2) to result in proteins that are substantially non-immunogenic or less immunogenic than any non-modified counterpart when use in vivo.

    摘要翻译： 本发明涉及特别用于人，特别是用于治疗用途的多肽。 所述多肽是修饰的多肽，其中所述修饰导致多肽在施用于人受试者时引起免疫应答的倾向降低。 本发明特别涉及人干扰素α和特异性干扰素α2（INFalpha2）的修饰，以产生当在体内使用时基本上不具有免疫原性或比任何未修饰的对应物更少免疫原性的蛋白质。

    Time-based metadata management system for digital media
    9.
    发明授权
    Time-based metadata management system for digital media 有权

    公开(公告)号：US10095367B1

    公开(公告)日：2018-10-09

    申请号：US12905520

    申请日：2010-10-15

    申请人： Matthew G. Berry ,  Tim Jones ,  Isaac Kunkel

    发明人： Matthew G. Berry ,  Tim Jones ,  Isaac Kunkel

    IPC分类号： G06F3/048

    摘要： Managing metadata associated with a digital media asset includes selecting the digital media asset, displaying the digital media asset in a filmstrip format that presents one or more scenes from the digital media asset along a timeline, wherein each scene corresponds with an underlying point in time along the timeline, and wherein the digital media asset has a start time and an end time that define the timeline, displaying at least one track in timeline alignment with the film strip format wherein the at least one track corresponds with a type of metadata associated with the digital media asset, and displaying on the at least one track, one or more segments, wherein each segment has a start point and an end point along the timeline and wherein each respective segment represents a span of time in which the type of metadata occurs within the digital media asset.

    Directional stimulation lead and orientation system
    10.
    发明授权
    Directional stimulation lead and orientation system 有权
    定向刺激引导和定向系统

    公开(公告)号：US08224456B2

    公开(公告)日：2012-07-17

    申请号：US10996803

    申请日：2004-11-24

    申请人： Terry Daglow ,  Brian Franz ,  John H. Erickson ,  Sandy Hooper ,  Tim Jones

    发明人： Terry Daglow ,  Brian Franz ,  John H. Erickson ,  Sandy Hooper ,  Tim Jones

    IPC分类号： A61N1/00

    CPC分类号： A61N1/0551 ,  A61N1/0529

    摘要： A lead, method of manufacturing same, and system for stimulation is provided. The lead includes an insulative member or layer that masks a portion of the electrode(s) to effectively generate a directional lead that focuses or directs the stimulation to desired location(s). In another embodiment, the lead further includes a marking system to allow a clinician to orient the directional lead, as desired, while the lead is within a body.

    摘要翻译： 提供铅，制造方法和刺激系统。 引线包括掩蔽电极的一部分的绝缘构件或层，以有效地产生将刺激聚焦或引导到所需位置的方向引线。 在另一个实施例中，引线还包括标记系统，以允许临床医生在引线位于身体内时根据需要定向方向引线。