公开(公告)号：US20090155763A1

公开(公告)日：2009-06-18

申请号：US12172990

申请日：2008-07-14

申请人： Keith M. Rosiello ,  Henrik Clausen ,  Hans Wandall ,  Thomas P. Stossel ,  John H. Hartwig ,  Karin M. Hoffmeister

发明人： Keith M. Rosiello ,  Henrik Clausen ,  Hans Wandall ,  Thomas P. Stossel ,  John H. Hartwig ,  Karin M. Hoffmeister

IPC分类号： C12N5/02

CPC分类号： A61K35/19 ,  A01N1/00 ,  C12N5/0644

摘要： The present invention provides modified platelets having a reduced platelet clearance and methods for reducing platelet clearance. Also provided are compositions for the preservation of platelets. The invention also provides methods for making a pharmaceutical composition containing the modified platelets and for administering the pharmaceutical composition to a mammal to mediate hemostasis.

摘要翻译： 本发明提供具有降低的血小板清除率的改良血小板和减少血小板清除率的方法。 还提供了用于保存血小板的组合物。 本发明还提供了制备含有改性血小板的药物组合物和用于将哺乳动物给药以介导止血的方法。

公开(公告)号：US07449316B2

公开(公告)日：2008-11-11

申请号：US11317196

申请日：2005-12-22

申请人： Henrik Clausen ,  Eric Paul Bennett ,  Rudi Steffensen

发明人： Henrik Clausen ,  Eric Paul Bennett ,  Rudi Steffensen

IPC分类号： C12N9/10 ,  C12P19/00 ,  C12P21/04 ,  C12Q1/00 ,  C12Q1/68 ,  C12N1/20 ,  C12N15/00 ,  C07H21/04

CPC分类号： C12N9/1051

摘要： A novel gene defining a novel enzyme UDP-galactose: β-D-galactose-R 4-α-D-galactosyltransferase, termed α4Gal-T1, with unique enzymatic properties is disclosed. The invention provides isolated DNA molecules and DNA constructs encoding α4Gal-T1 and derivatives thereof by way of amino acid deletion, substitution or insertion exhibiting α4Gal-T1 activity, as well as cloning and expression vectors including such DNA, host cells comprising DNA encoding α4Gal-T1, and recombinant methods for providing α4Gal-T1. The enzyme α4Gal-T1 and α4Gal-active derivatives thereof are disclosed. Further, the invention discloses methods of obtaining α1, 4galactosyl glycosylated glycosphingolipids by use of an enzymatically active α4Gal-T1 protein thereof or by using cells stably transfected with a vector including DNA encoding an enzymatically active α4Gal-T1 protein as an expression system for recombinant production of such glycosphingolipids. Also a method for the identification of DNA sequence variations in the α4Gal-T1-coding exon by PCR, and detecting the presence of DNA sequence variation, are disclosed.

摘要翻译： 公开了一种新颖的基因，其定义了具有独特的酶学性质的新型酶UDP-半乳糖：β-D-半乳糖-R 4-α-D-半乳糖基转移酶，称为α4Gal-T1。 本发明提供分离的DNA分子和编码α4Gal-T1及其衍生物的DNA构建体，其通过氨基酸缺失，取代或插入表现出α4Gal-T1活性，以及​​克隆和表达载体，包括此类DNA，宿主细胞包含编码α4Gal- T1和用于提供α4Gal-T1的重组方法。 公开了其α4Gal-T1和α4Gal活性衍生物。 此外，本发明公开了通过使用其酶促活化的α4Gal-T1蛋白或通过使用包含编码酶活性α4Gal-T1蛋白的DNA稳定转染的细胞作为重组生产的表达系统来获得α1，4半乳糖基糖基化糖苷脂的方法 的这种糖鞘醇。 还公开了通过PCR鉴定α4Gal-T1编码外显子中的DNA序列变异以及检测DNA序列变异的存在的方法。

公开(公告)号：US20080242846A1

公开(公告)日：2008-10-02

申请号：US11843588

申请日：2007-08-22

申请人： Shawn DeFrees ,  David A. Zopf ,  Zhi-Guang Wang ,  Henrik Clausen

发明人： Shawn DeFrees ,  David A. Zopf ,  Zhi-Guang Wang ,  Henrik Clausen

IPC分类号： C07K14/00 ,  C07K1/00

CPC分类号： A61K38/193 ,  C07K1/1077 ,  C07K9/00 ,  C07K9/001 ,  C07K14/535

摘要： The present invention provides polypeptides that include an O-linked glycosylation site that is not present in the wild-type peptide. The polypeptides of the invention include glycoconjugates in which a species such as a water-soluble polymer, a therapeutic agent of a biomolecule is covalently linked through an intact O-linked glycosyl residue to the polypeptide. Also provided are methods of making the peptides of the invention and methods, pharmaceutical compositions containing the peptides and methods of treating, ameliorating or preventing diseased in mammals by administering an amount of a peptide of the invention sufficient to achieve the desired response.

摘要翻译： 本发明提供了包含在野生型肽中不存在的O-连接的糖基化位点的多肽。 本发明的多肽包括糖缀合物，其中诸如水溶性聚合物的物质，生物分子的治疗剂通过完整O-连接的糖基残基与多肽共价连接。 还提供了制备本发明的肽和方法的方法，含有肽的药物组合物和通过施用足够达到所需反应的量的本发明的肽来治疗，改善或预防哺乳动物患病的方法。

公开(公告)号：US20080102083A1

公开(公告)日：2008-05-01

申请号：US10556094

申请日：2004-05-07

申请人： Shawn DeFrees ,  Henrik Clausen

发明人： Shawn DeFrees ,  Henrik Clausen

IPC分类号： A61K39/00 ,  A61P43/00 ,  C07H21/04 ,  C07K16/00 ,  C12N5/00 ,  C12P21/04

CPC分类号： C07K14/61 ,  A61K38/00

摘要： The present invention relates to mutants of human growth hormone, which contain newly introduced N-linked or O-linked glycosylation site(s), such that these recombinantly produced polypeptides have glycosylation patterns distinctly different from that of the naturally occurring human growth hormone. The polynucleotide coding sequences for the mutants, expression cassettes comprising the coding sequences, cells expressing the mutants, and methods for producing the mutants are also disclosed. Further disclosed are pharmaceutical compositions comprising the mutants and method for using the mutants.

摘要翻译： 本发明涉及包含新引入的N-连接或O-连接的糖基化位点的人生长激素的突变体，使得这些重组产生的多肽具有与天然存在的人生长激素明显不同的糖基化模式。 还公开了突变体的多核苷酸编码序列，包含编码序列的表达盒，表达突变体的细胞，以及用于产生突变体的方法。 还公开了包含突变体和使用突变体的方法的药物组合物。

公开(公告)号：US07078206B2

公开(公告)日：2006-07-18

申请号：US10843723

申请日：2004-05-11

申请人： Tilo Schwientek ,  Henrik Clausen

发明人： Tilo Schwientek ,  Henrik Clausen

IPC分类号： C12N9/10 ,  C07K1/00

CPC分类号： C12N9/1051 ,  A61K38/00 ,  A61K48/00

摘要： A novel gene defining a novel human UDP-GlcNAc: Galβ1-3GalNAcα β1,6GlcNAc-transferase, termed C2GnT3, with unique enzymatic properties is disclosed. The enzymatic activity of C2GnT3 is shown to be distinct from that of previously identified enzymes of this gene family. The invention discloses isolated DNA molecules and DNA constructs encoding C2GnT3 and derivatives thereof by way of amino acid deletion, substitution or insertion exhibiting C2GnT3 activity, as well as cloning and expression vectors including such DNA, cells transfected with the vectors, and recombinant methods for providing C2GnT3. The enzyme C2GnT3 and C2GnT3-active derivatives thereof are disclosed, in particular soluble derivatives comprising the catalytically active domain of C2GnT3. Further, the invention discloses methods of obtaining 1,6-N-acetylglucosaminyl glycosylated saccharides, glycopeptides or glycoproteins by use of an enzymically active C2GnT3 protein or fusion protein thereof or by using cells stably transfected with a vector including DNA encoding an enzymatically active C2GnT3 protein as an expression system for recombinant production of such glycopeptides or glycoproteins. Methods are disclosed for the identification of agents with the ability to inhibit or stimulate the biological activity of C2GnT3. Furthermore, methods of using C2GnT3 in the structure-based design of inhibitors or stimulators thereof are also disclosed in the invention. Also a method for the identification of DNA sequence variations in the C2GnT3 gene by isolating DNA from a patient, amplifying C2GnT3-coding exons by PCR, and detecting the presence of DNA sequence variation, are disclosed.

摘要翻译： 公开了一种定义新型人类UDP-GlcNAc：Galbeta1-3GalNAcalphaβ1,6GlcNAc转移酶（称为C2GnT3），具有独特的酶学性质的新基因。 C2GnT3的酶活性显示与以前鉴定的该基因家族酶的活性不同。 本发明公开了通过氨基酸缺失，表达C2GnT3活性的氨基酸缺失，取代或插入编码C2GnT3及其衍生物的分离的DNA分子和DNA构建体，以及包括这种DNA的克隆和表达载体，用载体转染的细胞，以及用于提供 C2GnT3。 公开了其C2GnT3和C2GnT3-活性衍生物，特别是包含C2GnT3的催化活性结构域的可溶性衍生物。 此外，本发明公开了通过使用酶活性C2GnT3蛋白或其融合蛋白或通过使用包含编码酶活性C2GnT3蛋白的DNA的载体稳定转染的细胞获得1,6- N - 乙酰葡糖胺基糖基化糖，糖肽或糖蛋白的方法 作为重组生产这种糖肽或糖蛋白的表达系统。 公开了用于鉴定具有抑制或刺激C2GnT3的生物学活性能力的试剂的方法。 此外，本发明还公开了在抑制剂或其刺激剂的基于结构的设计中使用C2GnT3的方法。 还公开了通过从患者中分离DNA，通过PCR扩增C2GnT3编码外显子并检测DNA序列变异的存在来鉴定C2GnT3基因中DNA序列变异的方法。

公开(公告)号：US20050042727A1

公开(公告)日：2005-02-24

申请号：US10939066

申请日：2004-09-09

申请人： Henrik Clausen ,  Tilo Schwientek

发明人： Henrik Clausen ,  Tilo Schwientek

IPC分类号： C12N15/09 ,  C12N1/15 ,  C12N1/19 ,  C12N1/21 ,  C12N5/10 ,  C12N9/10 ,  C12Q1/68 ,  C12P21/02 ,  C07H21/04 ,  C12N15/74 ,  C12P19/18

CPC分类号： C12N9/1051

摘要： A novel gene defining a novel human UDP-GlcNAc: Gal/Gl cNAcβ 1-3GalNAc αβ1, 6GlcNAc-transferase, termed C2/4GnT, with unique enzymatic properties is disclosed. The enzymatic activity of C2/4GnT is shown to be distinct from that of previously identified enzymes of this gene family. The invention discloses isolated DNA molecules and DNA constructs encoding C2/4GnT and derivatives thereof by way of amino acid deletion, substitution or insertion exhibiting C2/4GnT activity, as well as cloning and expression vectors including such DNA, cells transfected with the vectors, and recombinant methods for providing C2/4GnT. The enzyme C2/4GnT and C2/4GnT-active derivatives thereof are disclosed, in particular soluble derivatives comprising the catalytically active domain of C2/4GnT. Further, the invention discloses methods of obtaining 1,6-N-acetyl glucosaminyl glycosylated saccharides, glycopeptides or glycoproteins by use of an enzymically active C2/4GnT protein or fusion protein thereof or by using cells stably transfected with a vector including DNA encoding an enzymatically active C2/4GnT protein as an expression system for recombinant production of such glycopeptides or glycoproteins. Also a method for the identification for the identification of DNA sequence variations in the C2/4GnT gene by isolating DNA from a patient, amplifying C2/4GnT-coding exons by PCR, and detecting the presence of DNA sequence variation are disclosed.

摘要翻译： 公开了一种定义新型人类UDP-GlcNAc：Gal / GlcNAcbeta 1-3GalNAc alphabeta1,6GlcNAc转移酶，称为C2 / 4GnT，具有独特的酶学性质的新基因。 C2 / 4GnT的酶活性显示与以前鉴定的该基因家族酶的活性不同。 本发明公开了通过氨基酸缺失，C2 / 4GnT活性的氨基酸缺失，取代或插入编码C2 / 4GnT及其衍生物的分离的DNA分子和DNA构建体，以及包括这种DNA的克隆和表达载体，用载体转染的细胞，以及 提供C2 / 4GnT的重组方法。 公开了其C2 / 4GnT酶和C2 / 4GnT活性衍生物，特别是包含C2 / 4GnT的催化活性结构域的可溶性衍生物。 此外，本发明公开了通过使用酶活性的C2 / 4GnT蛋白或其融合蛋白或通过使用包含编码酶的DNA的载体稳定转染的细胞来获得1,6-N-乙酰氨基葡糖基糖基化糖，糖肽或糖蛋白的方法 活性C2 / 4GnT蛋白作为重组生产这种糖肽或糖蛋白的表达系统。 还公开了通过从患者分离DNA来鉴定C2 / 4GnT基因中DNA序列变异的方法，通过PCR扩增C2 / 4GnT编码的外显子，并检测DNA序列变异的存在。

公开(公告)号：US06558934B1

公开(公告)日：2003-05-06

申请号：US09118464

申请日：1998-07-17

申请人： Henrik Clausen ,  Eric Paul Bennett

发明人： Henrik Clausen ,  Eric Paul Bennett

IPC分类号： C12P2106

CPC分类号： C12N9/1051

摘要： A novel gene defining a novel enzyme in the UDP-D-galactose: &bgr;-N-acetyl-glucosamine &bgr;-1,4-galactosyltransferase family, termed &bgr;4Gal-T2, with unique enzymatic properties is disclosed. The enzymatic activity of &bgr;4Gal-T2 is shown to be distinct from that of previously identified enzymes of this gene family. The invention discloses isolated DNA molecules and DNA constructs encoding &bgr;4Gal-T2 and derivatives thereof by way of amino acid deletion, substitution or insertion exhibiting &bgr;4Gal-T2 activity, as well as cloning and expression vectors including such DNA, cells transfected with the vectors, and recombinant methods for providing &bgr;4Gal-T2. The enzyme &bgr;4Gal-T2 and &bgr;4Gal-T2-active derivatives thereof are disclosed, in particular soluble derivatives comprising the catalytically active domain of &bgr;4Gal-T2. Further, the invention discloses methods of obtaining &bgr;-1,4-galactosyl glycosylated saccharides, glycopeptides or glycoproteins by use of an enzymically active &bgr;4Gal-T2 protein or fusion protein thereof or by using cells stably transfected with a vector including DNA encoding an enzymatically active &bgr;4Gal-T2 protein as an expression system for recombinant production of such glycopeptides or glycoproteins. Also a method for the identification of DNA sequence variations in the &bgr;4Gal-T2 gene by isolating DNA from a patient, amplifying &bgr;4Gal-T2-coding exons by PCR, and detecting the presence of DNA sequence variation, are disclosed.

摘要翻译： 公开了在UDP-D-半乳糖:β-N-乙酰葡糖胺β-1,4-半乳糖基转移酶家族中定义新的酶的新基因，称为β4Gal-T2，具有独特的酶学性质。 β4Gal-T2的酶活性显示与以前鉴定的该基因家族酶的活性不同。 本发明公开了分离的DNA分子和编码β4Gal-T2的DNA构建体及其衍生物，通过氨基酸缺失，取代或插入显示β4Gal-T2活性，以及​​克隆和表达载体，包括这种DNA，用载体转染的细胞，以及 提供β4Gal-T2的重组方法。 公开了酶β4Gal-T2和β4Gal-T2-活性衍生物，特别是包含β4Gal-T2的催化活性结构域的可溶性衍生物。 此外，本发明公开了通过使用酶活性β4Gal-T2蛋白或其融合蛋白或通过使用包含编码酶活性的DNA的载体稳定转染的细胞获得β-1,4-半乳糖基糖基化糖，糖肽或糖蛋白的方法 β4Gal-T2蛋白作为重组生产这种糖肽或糖蛋白的表达系统。 还公开了通过从患者中分离DNA，通过PCR扩增β4Gal-T2编码外显子并检测DNA序列变异的存在来鉴定β4Gal-T2基因中的DNA序列变异的方法。

公开(公告)号：US5660834A

公开(公告)日：1997-08-26

申请号：US400480

申请日：1995-03-08

申请人： Thomas J. Kjeldsen ,  Henrik Clausen ,  Anil Singhal ,  Tatsushi Toyokuni ,  Helio K. Takahashi ,  Sen-Itiroh Hakomori

发明人： Thomas J. Kjeldsen ,  Henrik Clausen ,  Anil Singhal ,  Tatsushi Toyokuni ,  Helio K. Takahashi ,  Sen-Itiroh Hakomori

IPC分类号： A61K39/00 ,  C07K14/47 ,  C07K16/30 ,  A61K38/14 ,  A61K39/39 ,  C07K14/82

CPC分类号： C07K14/4727 ,  A61K39/0011 ,  C07K16/30 ,  A61K2039/55572 ,  A61K2039/6018 ,  A61K2039/6081 ,  A61K2039/645

摘要： A vaccine and method to prevent growth and replication of cancer cells that express a core structure of a mucin-type glycoprotein is disclosed. The vaccine comprises: (a) a pharmaceutically effective amount of an antigen comprising a purified mucin-type glycoprotein or a chemically synthesized mucin-type glycoprotein carbohydrate determinant conjugated to a carrier peptide or macromolecule, wherein said mucin-type glycoprotein expresses or carries the core structure of a mucin-type glycoprotein expressed on said cancer cells; and (b) a pharmaceutically acceptable carrier including natural or synthetic adjuvants. The method comprises administering the above-described vaccine to a host. A medicament and method for treating cancer wherein the cancer cells express a core structure of a mucin-type glycoprotein is disclosed. The medicament comprises: (a) a pharmaceutically effective amount of an anti-cancer antibody or fragment comprising a binding site thereof, said anti-cancer antibody having been produced against a purified core structure of a mucin-type glycoprotein; and (b) a pharmaceutically acceptable carrier, diluent or excipient. The method comprises administering the above-described medicament to a host.

摘要翻译： 公开了一种用于预防表达粘蛋白型糖蛋白的核心结构的癌细胞的生长和复制的疫苗和方法。 疫苗包含：（a）药学有效量的抗原，其包含与载体肽或大分子缀合的纯化的粘蛋白型糖蛋白或化学合成的粘蛋白型糖蛋白碳水化合物决定簇，其中所述粘蛋白型糖蛋白表达或携带核心 在所述癌细胞上表达的粘蛋白型糖蛋白的结构; 和（b）包括天然或合成佐剂的药学上可接受的载体。 该方法包括将上述疫苗给予宿主。 公开了一种治疗癌症的药物和方法，其中癌细胞表达粘蛋白型糖蛋白的核心结构。 药物包括：（a）药学有效量的抗癌抗体或包含其结合位点的片段，所述抗癌抗体是针对粘蛋白型糖蛋白的纯化核心结构产生的; 和（b）药学上可接受的载体，稀释剂或赋形剂。 该方法包括将上述药物施用于宿主。

公开(公告)号：US5418129A

公开(公告)日：1995-05-23

申请号：US803065

申请日：1991-12-06

申请人： Edward Nudelman ,  Anil Singhal ,  Henrik Clausen ,  Sen-itiroh Hakomori ,  Kazuo Muroi ,  Toshio Suda ,  Hisao Nojiri

发明人： Edward Nudelman ,  Anil Singhal ,  Henrik Clausen ,  Sen-itiroh Hakomori ,  Kazuo Muroi ,  Toshio Suda ,  Hisao Nojiri

IPC分类号： A61K38/00 ,  C07K16/30 ,  C12P21/08 ,  A01N1/02 ,  A61K39/395 ,  C07K15/28

CPC分类号： C07K16/30 ,  A61K38/00

摘要： A method of producing monoclonal antibodies that bind to tumor-associated gangliosides, the method comprising: (1) immunizing a host with tumor cells; (2) boosting the host with a suspension comprising a mixture of tumor cell membrane and at least one purified lactonized tumor-associated ganglioside; (3) boosting the host with an immunogen comprising a lactone of a tumor associated ganglioside adsorbed on or incorporated into a carrier; (4) fusing immunized cells from the host with myeloma cells to form hybridoma cells; (5) selecting hybridoma cells that produce antibody that binds to the ganglioside of step (3); (6) culturing the selected hybridoma cells; and (7) recovering the antibody.

摘要翻译： 一种产生与肿瘤相关神经节苷脂结合的单克隆抗体的方法，所述方法包括：（1）用肿瘤细胞免疫宿主; （2）用包含肿瘤细胞膜和至少一种经内化的内源性肿瘤相关神经节苷脂的混合物的悬浮液加强宿主; （3）用包含吸附在载体上或结合到载体中的肿瘤相关神经节苷脂的内酯的免疫原来加强宿主; （4）将来自宿主的免疫细胞与骨髓瘤细胞融合以形成杂交瘤细胞; （5）选择产生与步骤（3）的神经节苷脂结合的抗体的杂交瘤细胞; （6）培养所选择的杂交瘤细胞; 和（7）回收抗体。

公开(公告)号：US08517967B2

公开(公告)日：2013-08-27

申请号：US13291402

申请日：2011-11-08

申请人： Keith Rosiello ,  Henrik Clausen

发明人： Keith Rosiello ,  Henrik Clausen

IPC分类号： A61M37/00 ,  A61M1/02 ,  A61M1/36 ,  A61P7/02

CPC分类号： A01N1/0226 ,  A01N1/00 ,  A01N1/02

摘要： The present invention provides modified platelets having a reduced platelet clearance and methods for reducing platelet clearance. Also provided are compositions for the preservation of platelets. The invention also provides methods for making a pharmaceutical composition containing the modified platelets and for administering the pharmaceutical composition to a mammal to mediate hemostasis.

摘要翻译： 本发明提供具有降低的血小板清除率的改良血小板和减少血小板清除率的方法。 还提供了用于保存血小板的组合物。 本发明还提供了制备含有改性血小板的药物组合物和用于将哺乳动物给药以介导止血的方法。