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21. 发明授权

US07629163B2 Methods for producing modified glycoproteins 失效
标题翻译：生产改性糖蛋白的方法
公开(公告)号：US07629163B2
公开(公告)日：2009-12-08
申请号：US11271235
申请日：2005-11-10
申请人： Tillman U. Gerngross
发明人： Tillman U. Gerngross
IPC分类号： C12N1/15 , C07K14/00
CPC分类号： C12P21/005 , C07K2319/04 , C07K2319/05 , C12N1/14 , C12N9/1048 , C12N9/2488 , C12N15/79 , C12N15/80 , C12N15/81 , C12Y302/01 , C12Y302/01113
摘要： Cell lines having genetically modified glycosylation pathways that allow them to carry out a sequence of enzymatic reactions, which mimic the processing of glycoproteins in humans, have been developed. Recombinant proteins expressed in these engineered hosts yield glycoproteins more similar, if not substantially identical, to their human counterparts. The lower eukaryotes, which ordinarily produce high-mannose containing N-glycans, including unicellular and multicellular fungi are modified to produce N-glycans such as Man5GlcNAc2 or other structures along human glycosylation pathways. This is achieved using a combination of engineering and/or selection of strains which: do not express certain enzymes which create the undesirable complex structures characteristic of the fungal glycoproteins, which express exogenous enzymes selected either to have optimal activity under the conditions present in the fungi where activity is desired, or which are targeted to an organelle where optimal activity is achieved, and combinations thereof wherein the genetically engineered eukaryote expresses multiple exogenous enzymes required to produce “human-like” glycoproteins.
摘要翻译：已经开发了具有遗传修饰的糖基化途径的细胞系，其允许它们进行模拟人类中糖蛋白的加工的酶反应序列。在这些工程化宿主中表达的重组蛋白可以产生与其对应物更相似的糖蛋白（如果基本上不相同）。通常产生含有高甘露糖的N-聚糖（包括单细胞和多细胞真菌）的低等真核生物被修饰以产生N-聚糖如Man5GlcNAc2或沿着人糖基化途径的其它结构。这是使用以下工程和/或选择的组合实现的：不表达产生真菌糖蛋白特征的不合需要的复合结构的某些酶，其表达选择在真菌中存在的条件下具有最佳活性的外源酶其中需要活性或靶向实现最佳活性的细胞器，以及其组合，其中遗传工程真核生物表达产生“人样”糖蛋白所需的多种外源酶。

22. 发明授权

US07326681B2 Methods for producing modified glycoproteins 有权
标题翻译：生产改性糖蛋白的方法
公开(公告)号：US07326681B2
公开(公告)日：2008-02-05
申请号：US11240432
申请日：2005-09-30
申请人： Tillman U. Gerngross
发明人： Tillman U. Gerngross
IPC分类号： A61K38/14 , A61K38/00
CPC分类号： C12P21/005 , C07K2319/04 , C07K2319/05 , C12N1/14 , C12N9/1048 , C12N9/2488 , C12N15/79 , C12N15/80 , C12N15/81 , C12Y302/01 , C12Y302/01113
摘要： Cell lines having genetically modified glycosylation pathways that allow them to carry out a sequence of enzymatic reactions, which mimic the processing of glycoproteins in humans, have been developed. Recombinant proteins expressed in these engineered hosts yield glycoproteins more similar, if not substantially identical, to their human counterparts. The lower eukaryotes, which ordinarily produce high-mannose containing N-glycans, including unicellular and multicellular fungi are modified to produce N-glycans such as Man5GlcNAc2 or other structures along human glycosylation pathways. This is achieved using a combination of engineering and/or selection of strains which: do not express certain enzymes which create the undesirable complex structures characteristic of the fungal giycoproteins, which express exogenous enzymes selected either to have optimal activity under the conditions present in the fungi where activity is desired, or which are targeted to an organelle where optimal activity is achieved, and combinations thereof wherein the genetically engineered eukaryote expresses multiple exogenous enzymes required to produce “human-like” glycoproteins.
摘要翻译：已经开发了具有遗传修饰的糖基化途径的细胞系，其允许它们进行模拟人类中糖蛋白的加工的酶反应序列。在这些工程化宿主中表达的重组蛋白可以产生与其对应物更相似的糖蛋白（如果基本上不相同）。通常产生含有高甘露糖的N-聚糖（包括单细胞和多细胞真菌）的低等真核生物被修饰以产生N-聚糖，例如Man 3或GlcNAc 2 N或其它结构沿着人类糖基化途径。这是使用以下工程和/或选择的组合实现的：不表达产生真菌糖蛋白特征的不合需要的复合结构的某些酶，其表达选择在真菌中存在的条件下具有最佳活性的外源酶其中需要活性或靶向实现最佳活性的细胞器，以及其组合，其中遗传工程真核生物表达产生“人样”糖蛋白所需的多种外源酶。

23. 发明申请

US20060148035A1 Methods for producing modified glycoproteins 失效
标题翻译：生产改性糖蛋白的方法
公开(公告)号：US20060148035A1
公开(公告)日：2006-07-06
申请号：US11271235
申请日：2005-11-10
申请人： Tillman Gerngross
发明人： Tillman Gerngross
IPC分类号： C12P21/06 , C07H21/04 , C12N9/24 , C12N1/18 , C12N15/74
CPC分类号： C12P21/005 , C07K2319/04 , C07K2319/05 , C12N1/14 , C12N9/1048 , C12N9/2488 , C12N15/79 , C12N15/80 , C12N15/81 , C12Y302/01 , C12Y302/01113
摘要： Cell lines having genetically modified glycosylation pathways that allow them to carry out a sequence of enzymatic reactions, which mimic the processing of glycoproteins in humans, have been developed. Recombinant proteins expressed in these engineered hosts yield glycoproteins more similar, if not substantially identical, to their human counterparts. The lower eukaryotes, which ordinarily produce high-mannose containing N-glycans, including unicellular and multicellular fungi are modified to produce N-glycans such as Man5GlcNAc2 or other structures along human glycosylation pathways. This is achieved using a combination of engineering and/or selection of strains which: do not express certain enzymes which create the undesirable complex structures characteristic of the fungal glycoproteins, which express exogenous enzymes selected either to have optimal activity under the conditions present in the fungi where activity is desired, or which are targeted to an organelle where optimal activity is achieved, and combinations thereof wherein the genetically engineered eukaryote expresses multiple exogenous enzymes required to produce “human-like” glycoproteins.
摘要翻译：已经开发了具有遗传修饰的糖基化途径的细胞系，其允许它们进行模拟人类中糖蛋白的加工的酶反应序列。在这些工程化宿主中表达的重组蛋白可以产生与其对应物更相似的糖蛋白（如果基本上不相同）。通常产生含有高甘露糖的N-聚糖（包括单细胞和多细胞真菌）的低等真核生物被修饰以产生N-聚糖，例如Man 3或GlcNAc 2 N或其它结构沿着人类糖基化途径。这是使用以下工程和/或选择的组合实现的：不表达产生真菌糖蛋白特征的不合需要的复合结构的某些酶，其表达选择在真菌中存在的条件下具有最佳活性的外源酶其中需要活性或靶向实现最佳活性的细胞器，以及其组合，其中遗传工程真核生物表达产生“人样”糖蛋白所需的多种外源酶。

24. 发明申请

US20050208617A1 N-acetylglucosamintransferase III expression in lower eukaryotes 失效
标题翻译： N-乙酰葡萄糖转移酶III在低等真核生物中的表达
公开(公告)号：US20050208617A1
公开(公告)日：2005-09-22
申请号：US10680963
申请日：2003-10-07
申请人： Piotr Bobrowicz , Stephen Hamilton , Tilman Gerngross , Stefan Wildt , Byung-Kwon Choi , Juergen Nett , Robert Davidson
发明人： Piotr Bobrowicz , Stephen Hamilton , Tilman Gerngross , Stefan Wildt , Byung-Kwon Choi , Juergen Nett , Robert Davidson
IPC分类号： A61K38/00 , C07K14/39 , C07K14/47 , C12N1/18 , C12N9/10 , C12N15/12 , C12N15/74 , C12P21/00 , C12P21/06
CPC分类号： C07K14/39 , A61K38/00 , C07K2319/05 , C12N9/1051 , C12P21/005 , Y02A50/396
摘要： The present invention relates to eukaryotic host cells having modified oligosaccharides which may be modified further by heterologous expression of a set of glycosyltransferases, sugar transporters and mannosidases to become host-strains for the production of mammalian, e.g., human therapeutic glycoproteins. The process provides an engineered host cell which can be used to express and target any desirable gene(s) involved in glycosylation. Host cells with modified lipid-linked oligosaccharides are created or selected. N-glycans made in the engineered host cells exhibit GnTIII activity, which produce bisected N-glycan structures and may be modified further by heterologous expression of one or more enzymes, e.g., glycosyltransferases, sugar transporters and mannosidases, to yield human-like glycoproteins. For the production of therapeutic proteins, this method may be adapted to engineer cell lines in which any desired glycosylation structure may be obtained.
摘要翻译：本发明涉及具有修饰的寡糖的真核宿主细胞，其可以通过异源表达一组糖基转移酶，糖转运体和甘露糖苷酶进一步修饰，以成为用于产生哺乳动物例如人治疗性糖蛋白的宿主菌株。该方法提供了可用于表达和靶向参与糖基化的任何所需基因的工程化宿主细胞。制备或选择具有修饰的脂质连接寡糖的宿主细胞。在工程化的宿主细胞中制备的N-聚糖表现出GnTIII活性，其产生二等分的N-聚糖结构，并且可以通过异源表达一种或多种酶（例如糖基转移酶，糖转运蛋白和甘露糖苷酶）进一步修饰，以产生人样糖蛋白。为了生产治疗性蛋白质，该方法可适用于工程化可能获得任何所需糖基化结构的细胞系。

25. 发明公开

US20240287568A1 Engineered and Fully-Functional Customized Glycoproteins 审中-公开
公开(公告)号：US20240287568A1
公开(公告)日：2024-08-29
申请号：US18404577
申请日：2024-01-04
申请人： LimmaTech Biologics AG
发明人： Amirreza Faridmoayer , Manuela Mally , Rainer Follador
IPC分类号： C12P21/00 , C12N1/10 , C12N9/10 , C12R1/90
CPC分类号： C12P21/005 , C12N1/105 , C12N9/1029 , C12N9/1051 , C12N9/1081 , C07K2319/04 , C07K2319/05 , C12R2001/90 , C12Y203/01003 , C12Y204/01022 , C12Y204/01101 , C12Y204/01143 , C12Y204/99006
摘要： Described herein are compositions and methods of producing glycosylated proteins in vitro and in vivo. The methods include using host cells to produce glycosylated proteins. Also described herein are glycosylated proteins produced using such methods and uses thereof.

26. 发明授权

US11945865B2 Blockade of CD7 expression and chimeric antigen receptors for immunotherapy of T-cell malignancies 有权
公开(公告)号：US11945865B2
公开(公告)日：2024-04-02
申请号：US17865292
申请日：2022-07-14
申请人： National University of Singapore
发明人： Yi Tian Png , Natasha Vinanica , Takahiro Kamiya , Dario Campana
IPC分类号： A61K38/00 , A61K35/17 , A61K39/00 , A61P35/02 , C07K14/705 , C07K14/725 , C07K16/28 , C07K16/30
CPC分类号： C07K16/2803 , A61K35/17 , A61K39/001129 , A61P35/02 , C07K14/7051 , C07K14/70517 , C07K14/70578 , C07K16/3061 , A61K38/00 , A61K2039/5156 , A61K2039/5158 , A61K2039/804 , C07K2317/56 , C07K2317/622 , C07K2317/76 , C07K2319/02 , C07K2319/03 , C07K2319/04 , C07K2319/05 , C07K2319/33 , C07K2319/74
摘要： The present invention provides compositions comprising an anti-CD7 chimeric activating receptor (CAR) and an anti-CD7 protein expression blocker, and methods of using such compositions in cancer therapy.

27. 发明申请

US20180119164A1 Nucleic Acid Molecule and Uses Thereof 审中-公开
公开(公告)号：US20180119164A1
公开(公告)日：2018-05-03
申请号：US15568113
申请日：2016-04-20
申请人： Universität für Bodenkultur Wien
发明人： Andreas Loos , Hertha Steinkellner , Lukas Mach
IPC分类号： C12N15/82 , C12N9/10
CPC分类号： C12N15/8258 , C07K2319/01 , C07K2319/05 , C12N9/1051 , C12N9/1081 , C12N9/13 , C12N15/8243 , C12N15/8257 , C12Y204/01214 , C12Y204/99001 , C12Y208/0202
摘要： The present invention relates to a nucleic acid molecule encoding a) a modified tyrosylprotein sulfotransferase of a wildtype tyrosylprotein sulfotransferase, wherein the cytoplasmic transmembrane stem (CTS) region of the wild-type tyrosylprotein sulfotransferase is replaced by a heterologous CTS region, or b) a fusion protein comprising a catalytically active fragment of a tyrosylprotein sulfotransferase fused to a heterologous CTS region.

28. 发明申请

US20170022567A1 HIGH MAST2-AFFINITY POLYPEPTIDES AND USES THEREOF 审中-公开
标题翻译：高MAST2-AFFINITY多聚体及其用途
公开(公告)号：US20170022567A1
公开(公告)日：2017-01-26
申请号：US15265172
申请日：2016-09-14
申请人： INSTITUT PASTEUR , CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE , UNIVERSITE PIERRE ET MARIE CURIE (PARIS 6)
发明人： Christophe Prehaud , Monique Lafon , Nicolas Wolff , Zakir Khan , Elouan Terrien , Sandrine Vitry
IPC分类号： C12Q1/68 , C12N7/00 , C12Q1/70 , G01N33/50
CPC分类号： C12Q1/6883 , C07K14/005 , C07K14/435 , C07K2319/02 , C07K2319/05 , C07K2319/70 , C12N7/00 , C12N2799/027 , C12Q1/70 , C12Q2600/136 , C12Q2600/158 , C12Q2600/16 , G01N33/5023 , G01N33/5038 , G01N33/5058 , G01N2333/705
摘要： The invention relates to polypeptides containing a cytoplasmic domain ending with a MAST-2 binding domain, from 11 to 13 residues, the first two residues of which are S and W, and the last four residues of which are Q, T, R and L, the polypeptides presenting a high affinity for the PDZ domain of the human MAST2 protein. The invention also relates to polynucleotides, vectors, lentiviral particles, cells as well as compositions containing the same. The invention is also directed to the use of the polypeptides, polynucleotides, vectors, lentiviral particles, cells and compositions in the treatment and/or prevention of a disease, disorder or condition, which alters the Central Nervous System (CNS) and/or the Peripheral Nervous System (PNS). The invention also concerns molecular signatures of cellular genes to determine the neurosurvival and/or neuroprotection activity of a molecule.
摘要翻译：本发明涉及含有以MAST-2结合域结束的胞质结构域的多肽，11至13个残基，其前两个残基为S和W，最后4个残基为Q，T，R和L ，对人MAST2蛋白的PDZ结构域具有高亲和力的多肽。本发明还涉及多核苷酸，载体，慢病毒颗粒，细胞以及含有它们的组合物。本发明还涉及多肽，多核苷酸，载体，慢病毒颗粒，细胞和组合物在治疗和/或预防疾病，病症或病症中的用途，其改变中枢神经系统（CNS）和/或外周神经系统（PNS）。本发明还涉及细胞基因的分子特征，以确定分子的神经营养和/或神经保护活性。

29. 发明申请

US20160068880A1 METHODS FOR PRODUCING MODIFIED GLYCOPROTEINS 审中-公开
标题翻译：生产改性糖蛋白的方法
公开(公告)号：US20160068880A1
公开(公告)日：2016-03-10
申请号：US14927519
申请日：2015-10-30
申请人： GlycoFi, Inc.
发明人： Tillman U. Gerngross
IPC分类号： C12P21/00 , C12N9/24 , C12N15/81
CPC分类号： C12P21/005 , C07K2319/04 , C07K2319/05 , C12N1/14 , C12N9/1048 , C12N9/2488 , C12N15/79 , C12N15/80 , C12N15/81 , C12Y302/01 , C12Y302/01113
摘要： Cell lines having genetically modified glycosylation pathways that allow them to carry out a sequence of enzymatic reactions, which mimic the processing of glycoproteins I humans, have been developed. Recombinant proteins expressed in these engineered hosts yield glycoproteins more similar, if not substantially identical, to their human counterparts. The lower eukaryotes, which ordinarily produce high-mannose containing N-glycans such as Man5GlcNAc2 or other structures along human glycosylation pathways. This is achieved using a combination of engineering and/or selection of strains which: do not express certain enzymes which create the undesirable complex structures characteristic of the fungal glycoproteins, which express exogenous enzymes selected either to have optimal activity under the conditions present in the fungi where activity is desired, or which are targeted to an organelle where optimal activity is achieved, and combinations thereof wherein the genetically engineered eukaryote expresses multiple exogenous enzymes required to produce “human-like” glycoproteins.
摘要翻译：已经开发了具有遗传修饰的糖基化途径的细胞系，其允许它们进行模拟I型糖蛋白的加工的酶反应序列。在这些工程化宿主中表达的重组蛋白可以产生与其对应物更相似的糖蛋白（如果基本上不相同）。低等真核生物通常产生含有甘露聚糖的高聚甘露，如Man5GlcNAc2或其他结构沿着人类糖基化途径。这是使用以下工程和/或选择的组合实现的：不表达产生真菌糖蛋白特征的不合需要的复合结构的某些酶，其表达选择在真菌中存在的条件下具有最佳活性的外源酶其中需要活性或靶向实现最佳活性的细胞器，以及其组合，其中遗传工程真核生物表达产生“人样”糖蛋白所需的多种外源酶。

30. 发明申请

US20150203890A1 PRODUCTION OF SIALYLATED N-GLYCANS IN LOWER EUKARYOTES 审中-公开
标题翻译：在较低的核酸中生产广泛的N-糖类
公开(公告)号：US20150203890A1
公开(公告)日：2015-07-23
申请号：US14628392
申请日：2015-02-23
申请人： GlycoFi, Inc.
发明人： Stephen R. Hamilton
IPC分类号： C12P21/00
CPC分类号： C12P21/005 , C07K2319/036 , C07K2319/05 , C07K2319/055 , C12N9/1081 , C12N9/2402 , C12Y302/01018
摘要： The present invention relates to eukaryotic host cells which have been modified to produce sialylated glycoproteins by the heterologous expression of a set of glycosyltransferases, including sialyltransferase and/or trans-sialidase, to become host-strains for the production of mammalian, e.g., human therapeutic glycoproteins. Novel eukaryotic host cells expressing a CMP-sialic acid biosynthetic pathway for the production of sialylated glycoproteins are also provided. The invention provides nucleic acid molecules and combinatorial libraries which can be used to successfully target and express mammalian enzymatic activities (such as those involved in sialylation) to intracellular compartments in a eukaryotic host cell. The process provides an engineered host cell which can be used to express and target any desirable gene(s) involved in glycosylation.
摘要翻译：本发明涉及通过异源表达一组糖基转移酶（包括唾液酸转移酶和/或反式唾液酸酶）而被修饰以产生唾液酸化糖蛋白的真核宿主细胞，以成为用于产生哺乳动物例如人类治疗的宿主菌株糖蛋白。还提供了表达用于产生唾液酸化糖蛋白的CMP-唾液酸生物合成途径的新型真核宿主细胞。本发明提供了可用于成功靶向并表达哺乳动物酶活性（例如参与唾液酸化的那些）的核酸分子和组合文库给真核宿主细胞中的细胞内区室。该方法提供了可用于表达和靶向参与糖基化的任何所需基因的工程化宿主细胞。

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