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Patent Agency Ranking
公开(公告)号：US20160176926A1
公开(公告)日：2016-06-23
申请号：US14860381
申请日：2015-09-21
Applicant: AMGEN INC.
Inventor： Hosung MIN , Hailing HSU , Fei XIONG
CPC classification number: C07K7/08 , A61K38/00 , A61K38/10 , C07K1/047 , C07K14/001 , C07K14/4702 , C07K14/7151 , C07K16/241 , C07K2319/30 , C07K2319/74 , C12N15/1037 , C40B40/02
Abstract: The present invention concerns therapeutic agents that modulate the activity of TALL-1. In accordance with the present invention, modulators of TALL-1 may comprise an amino acid sequence Dz2Lz4 wherein z2 is an amino acid residue and z4 is threonyl or isoleucyl. Exemplary molecules comprise a sequence of the formulae (SEQ. ID. NO: 100) a1a2a3CDa6La8a9a10Ca12a13a14, (SEQ. ID. NO: 104) b1b2b3Cb6Db8Lb10b11b12b13b14Cb16b17b18 (SEQ. ID. NO: 105) c1c2c3Cc5Dc7Lc9c10c11c12c13c14Cc16c17c18 (SEQ. ID. NO: 106) d1d2d3Cd5d6d7WDd10Ld13d14d15Ld16d17d18 (SEQ. ID. NO: 107) e1e2e3Ce5e6e7De9Le11Ke13ce15e16e17e18 (SEQ. ID NO: 109) f1f2f3Kf5Df7Lf9f10Qf12f13f14 wherein the substituents are as defined in the specification. The invention further comprises compositions of matter of the formula (X1)a—V1—(X2)b wherein V1 is a vehicle that is covalently attached to one or more of the above TALL-1 modulating compositions of matter. The vehicle and the TALL-1 modulating composition of matter may be linked through the N- or C-terminus of the TALL-1 modulating portion. The preferred vehicle is an Fc domain, and the preferred Fc domain is an IgG Fc domain.
Abstract translation: 本发明涉及调节TALL-1活性的治疗剂。 根据本发明，TALL-1的调节剂可以包含氨基酸序列Dz2Lz4，其中z2是氨基酸残基，z4是苏氨酰基或异亮氨酰基。 示例性分子包括下式的一个序列（SEQ。ID NO：100）a1a2a3CDa6La8a9a10Ca12a13a14，（SEQ ID NO：104）b1b2b3Cb6Db8Lb10b11b12b13b14Cb16b17b18（SEQ ID。NO：105）c1c2c3Cc5Dc7Lc9c10c11c12c13c14Cc16c17c18（SEQ ID。NO：106）d1d2d3Cd5d6d7WDd10Ld13d14d15Ld16d17d18（ SEQ ID NO：107）e1e2e3Ce5e6e7De9Le11Ke13ce15e16e17e18（SEQ ID NO：109）f1f2f3Kf5Df7Lf9f10Qf12f13f14其中取代基如说明书中所定义。 本发明还包括式（X1）a-V1-（X2）b的物质的组合物，其中V1是共价连接到一种或多种上述TALL-1调节组合物的载体。 载体和TALL-1调节组合物可以通过TALL-1调节部分的N末端或C末端连接。 优选的载体是Fc结构域，优选的Fc结构域是IgG Fc结构域。
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公开(公告)号：US20140234334A1
公开(公告)日：2014-08-21
申请号：US13938141
申请日：2013-07-09
Applicant: AMGEN INC.
Inventor： Hosung MIN , Hailing HSU , Fei XIONG
CPC classification number: C07K7/08 , A61K38/00 , A61K38/10 , C07K1/047 , C07K14/001 , C07K14/4702 , C07K14/7151 , C07K16/241 , C07K2319/30 , C07K2319/74 , C12N15/1037 , C40B40/02
Abstract: The present invention concerns therapeutic agents that modulate the activity of TALL-1. In accordance with the present invention, modulators of TALL-1 may comprise an amino acid sequence Dz2Lz4 wherein z2 is an amino acid residue and z4 is threonyl or isoleucyl. Exemplary molecules comprise a sequence of the formulae (SEQ. ID. NO: 100) a1a2a3CDa6La8a9a10Ca12a13a14, (SEQ. ID. NO: 104) b1b2b3Cb5b6Db8Lb10b11b12b13b14Cb16b17b18 (SEQ. ID. NO: 105) c1c2c3Cc5Dc7Lc9c10c11c12c13c14Cc16c17c18 (SEQ. ID. NO: 106) d1d2d3Cd5d6d7WDd10Ld13d14d15Ld16d17d18 (SEQ. ID. NO: 107) e1e2e3Ce5e6e7De9Le11Ke13Ce15e16e17e18 (SEQ. ID NO: 109) f1f2f3Kf5Df7Lf9f10Qf12f13f14 wherein the substituents are as defined in the specification. The invention further comprises compositions of matter of the formula (X1)a—V1—(X2)b wherein V1 is a vehicle that is covalently attached to one or more of the above TALL-1 modulating compositions of matter. The vehicle and the TALL-1 modulating composition of matter may be linked through the N- or C-terminus of the TALL-1 modulating portion. The preferred vehicle is an Fc domain, and the preferred Fc domain is an IgG Fc domain.
Abstract translation: 本发明涉及调节TALL-1活性的治疗剂。 根据本发明，TALL-1的调节剂可以包含氨基酸序列Dz2Lz4，其中z2是氨基酸残基，z4是苏氨酰基或异亮氨酰基。 示例性分子包括下式的一个序列（SEQ。ID NO：100）a1a2a3CDa6La8a9a10Ca12a13a14，（SEQ ID NO：104）b1b2b3Cb5b6Db8Lb10b11b12b13b14Cb16b17b18（SEQ ID。NO：105）c1c2c3Cc5Dc7Lc9c10c11c12c13c14Cc16c17c18（SEQ ID。NO：106）d1d2d3Cd5d6d7WDd10Ld13d14d15Ld16d17d18（ SEQ ID NO：107）e1e2e3Ce5e6e7De9Le11Ke13Ce15e16e17e18（SEQ ID NO：109）f1f2f3Kf5Df7Lf9f10Qf12f13f14其中取代基如说明书中所定义。 本发明还包括式（X1）a-V1-（X2）b的物质的组合物，其中V1是共价连接到一种或多种上述TALL-1调节组合物的载体。 载体和TALL-1调节组合物可以通过TALL-1调节部分的N末端或C末端连接。 优选的载体是Fc结构域，优选的Fc结构域是IgG Fc结构域。
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公开(公告)号：US20190151463A1
公开(公告)日：2019-05-23
申请号：US16206899
申请日：2018-11-30
Applicant: AMGEN INC.
Inventor： Colin V. GEGG , Kenneth W. WALKER , Leslie P. MIRANDA , Fei XIONG
Abstract: Disclosed is a process for preparing a pharmacologically active compound, in which at least one internal conjugation site of an Fc domain sequence is selected that is amenable to conjugation of an additional functional moiety by a defined conjugation chemistry through the side chain of an amino acid residue at the conjugation site. An appropriate amino acid residue for conjugation may be present in a native Fc domain at the conjugation site or may be added by insertion (i.e., between amino acids in the native Fc domain) or by replacement (i.e., removing amino acids and substituting different amino acids). In the latter case, the number of amino acids added need not correspond to the number of amino acids removed from the previously existing Fc domain. This technology may be used to produce useful compositions of matter and pharmaceutical compositions containing them. A DNA encoding the inventive composition of matter, an expression vector containing the DNA, and a host cell containing the expression vector are also disclosed.
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公开(公告)号：US20160000932A1
公开(公告)日：2016-01-07
申请号：US14796502
申请日：2015-07-10
Applicant: AMGEN INC.
Inventor： Colin V. GEGG , Kenneth W. WALKER , Leslie P. MIRANDA , Fei XIONG
CPC classification number: A61K38/02 , A61K47/60 , A61K47/68 , A61K47/6817 , C07K16/00 , C07K17/00 , C07K2317/40 , C07K2317/52
Abstract: Disclosed is a process for preparing a pharmacologically active compound, in which at least one internal conjugation site of an Fc domain sequence is selected that is amenable to conjugation of an additional functional moiety by a defined conjugation chemistry through the side chain of an amino acid residue at the conjugation site. An appropriate amino acid residue for conjugation may be present in a native Fc domain at the conjugation site or may be added by insertion (i.e., between amino acids in the native Fc domain) or by replacement (i.e., removing amino acids and substituting different amino acids). In the latter case, the number of amino acids added need not correspond to the number of amino acids removed from the previously existing Fc domain. This technology may be used to produce useful compositions of matter and pharmaceutical compositions containing them. A DNA encoding the inventive composition of matter, an expression vector containing the DNA, and a host cell containing the expression vector are also disclosed.
Abstract translation: 公开了制备药理活性化合物的方法，其中选择Fc结构域序列的至少一个内部缀合位点，其适于通过定义的缀合化学通过氨基酸残基的侧链与另外的功能部分缀合 在共轭位点。 用于缀合的合适的氨基酸残基可以在缀合位点处的天然Fc结构域中存在，或者可以通过插入（即天然Fc结构域中的氨基酸之间）或替换（即，除去氨基酸并用不同的氨基 酸）。 在后一种情况下，加入的氨基酸数不需要对应于从先前存在的Fc结构域去除的氨基酸的数目。 该技术可用于生产含有它们的物质和药物组合物的有用组合物。 还公开了编码本发明组合物的DNA，含有该DNA的表达载体和含有表达载体的宿主细胞。
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公开(公告)号：US20140234945A1
公开(公告)日：2014-08-21
申请号：US14157325
申请日：2014-01-16
Applicant: Amgen Inc.
Inventor： Kenneth W. WALKER , Fei XIONG
IPC: C07K14/47
CPC classification number: C07K14/47 , A61K38/043 , A61K38/10 , A61K38/20 , A61K38/29 , A61K47/58 , A61K47/60 , A61K47/61 , A61K47/643 , C07K2319/31
Abstract: The present invention provides a means for increasing the serum half-life of a selected biologically active agent by utilizing transthyretin (TTR) as a fusion partner with a biologically active agent. Specifically, the present invention provides substantially homogenous preparations of TTR (or a TTR variant)-biologically active agent fusions and PEG-TTR (PEG-TTR variant)-biologically active agent fusions. As compared to the biologically active agent alone, the TTR-biologically active agent fusion and/or PEG-TTR-biologically active agent fusion has substantially increased serum half-life.
Abstract translation: 本发明提供了通过利用转甲状腺素蛋白（TTR）作为与生物活性剂的融合配偶体来提高选择的生物活性剂的血清半衰期的方法。 具体地说，本发明提供基本均匀的TTR（或TTR变体） - 生物活性剂融合物和PEG-TTR（PEG-TTR变体） - 生物活性剂融合物的制剂。 与单独的生物活性剂相比，TTR-生物活性剂融合和/或PEG-TTR-生物活性剂融合物具有显着增加的血清半衰期。
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