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31. 发明申请

WO0185215A9 METHODS OF MODULATING FUNCTIONS OF POLYPEPTIDE GALNAC-TRANSFERASES AND OF SCREENING TEST SUBSTANCES TO FIND AGENTS HEREFOR, PHARMACEUTICAL COMPOSITIONS COMPRISING SUCH AGENTS AND THE USE OF SUCH AGENTS FOR PREPARING MEDICAMENTS 审中-公开
标题翻译：调查多肽GALNAC转移功能的方法和筛选试验物质，以查找其中的药剂，包含这些药剂的药物组合物和这些药剂用于制备药物的用途
公开(公告)号：WO0185215A9
公开(公告)日：2002-01-24
申请号：PCT/DK0100328
申请日：2001-05-10
申请人： CLAUSEN HENRIK , HASSAN HELLE , REIS CELSO ALBUQUERQUE , BENNETT ERIC PAUL
发明人： CLAUSEN HENRIK , HASSAN HELLE , REIS CELSO ALBUQUERQUE , BENNETT ERIC PAUL
IPC分类号： A61K38/00 , A61K38/14 , A61K38/17 , C12Q1/48 , A61K45/00
CPC分类号： C12Q1/48 , A61K38/005 , A61K38/14 , A61K38/1709 , G01N2333/91102 , G01N2500/00 , G01N2500/10
摘要： Attachment of O-glycans to proteins is controlled by a large family of homologous polypeptide GalNAc-transferases. Polypeptide GalNAc-transferases contain a C-terminal sequence with similarity to lectins. This invention discloses that the putative lectin domains of GalNAc-transferase isoforms, GalNAc-T4, -T7, -T2, and T3, are functional and recognize carbohydrates, glycopeptides, and peptides. These lectin domains have different binding specificities and modulate the functions of GalNAc-transferase isoforms differently. The lectin domains of GalNAc-T- and -T7 directs the glycopeptide specificities of these enzymes, while the lectin domains of GalNAc-T2 and -T3 directs broadening of donor substrate specificities to include UDP-Gal. Selective inhibitors of these functions that do not eliminate general catalytic activities are disclosed. Such inhibitors disclosed include free sugars, aryl-sugar derivatives, and glycopeptides. Inhibitors of GalNAc-transferase lectin domains are useful for altering the O-glycosylation capacity of cells, tissues, and organisms, and such agents may also interfere with other binding functions involved in intracellular sorting and secretion events.
摘要翻译： O-聚糖对蛋白质的附着由大量的同源多肽GalNAc转移酶家族控制。多肽GalNAc转移酶含有与凝集素相似的C-末端序列。本发明公开了GalNAc转移酶同工型，GalNAc-T4，-T7，-T2和T3的推定凝集素结构域是功能性的并识别碳水化合物，糖肽和肽。这些凝集素结构域具有不同的结合特异性，并且不同地调节GalNAc转移酶同工型的功能。 GalNAc-T和-T7的凝集素结构域指导这些酶的糖肽特异性，而GalNAc-T2和-T3的凝集素结构域则指导供体底物特异性的扩大以包括UDP-Gal。公开了不消除一般催化活性的这些功能的选择性抑制剂。所公开的抑制剂包括游离糖，芳基糖衍生物和糖肽。 GalNAc转移酶凝集素结构域的抑制剂可用于改变细胞，组织和生物体的O-糖基化能力，并且这些试剂也可能干扰参与细胞内分选和分泌事件的其它结合功能。

32. 发明专利

CA2552892C O-LINKED GLYCOSYLATION OF PEPTIDES 未知
公开(公告)号：CA2552892C
公开(公告)日：2014-08-05
申请号：CA2552892
申请日：2005-01-10
申请人： NEOSE TECHNOLOGIES INC
发明人： DEFREES SHAWN , ZOPF DAVID A , WANG ZHI-GUANG , CLAUSEN HENRIK
IPC分类号： C12N15/27 , A61K38/14 , A61K38/19 , A61K38/21 , A61K38/27 , A61P5/00 , C07K1/107 , C07K9/00 , C07K14/00 , C07K14/535 , C07K14/56 , C07K14/61 , C12N1/21 , C12N5/10 , C12N15/18 , C12N15/21 , C12N15/63 , C12P19/00 , C12P21/02
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.

33. 发明专利

AU2006203792A1 Glycopegylated Granulocyte Colony Stimulating Factor 未知
公开(公告)号：AU2006203792A1
公开(公告)日：2006-07-13
申请号：AU2006203792
申请日：2006-01-10
申请人： NEOSE TECHNOLOGIES INC
发明人： ZOPF DAVID A , BOWE CARYN , DEFREES SHAWN , TAUDTE SUSANN , WILLETT WALTER S , CLAUSEN HENRIK , FELO MICHAEL
IPC分类号： A61K38/19 , C07K14/535
摘要： The present invention provides conjugates between Granulocyte Colony Stimulating Factor and PEG moieties. The conjugates are linked via an intact glycosyl linking group that is interposed between and covalently attached to the peptide and the modifying group. The conjugates are formed from both glycosylated and unglycosylated peptides by the action of a glycosyltransferase. The glycosyltransferase ligates a modified sugar moiety onto either an amino acid or glycosyl residue on the peptide. Also provided are pharmaceutical formulations including the conjugates. Methods for preparing the conjugates are also within the scope of the invention.

34. 发明专利

CA2552892A1 O-LINKED GLYCOSYLATION OF PEPTIDES 未知
公开(公告)号：CA2552892A1
公开(公告)日：2005-08-04
申请号：CA2552892
申请日：2005-01-10
申请人： NEOSE TECHNOLOGIES INC
发明人： CLAUSEN HENRIK , WANG ZHI-GUANG , ZOPF DAVID A , DEFREES SHAWN
IPC分类号： C12N15/27 , A61K38/14 , A61K38/19 , A61K38/21 , A61K38/27 , A61P5/00 , C07K1/107 , C07K9/00 , C07K14/00 , C07K14/535 , C07K14/56 , C07K14/61 , C12N1/21 , C12N5/10 , C12N15/18 , C12N15/21 , C12N15/63 , C12P19/00 , C12P21/02
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 suc h as a water-soluble polymer, a therapeutic agent of a biomolecule is covalent ly 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.

35. 发明申请

WO2011054359A3 METHOD FOR EARLY DETECTION OF CANCER USING O - GLYCOSYLATED MUCIN PEPTIDES OR CORRESPONDING MONOCLONAL ANTIBODIES 审中-公开
标题翻译：早期检测使用O-糖苷化的胶原蛋白或相应单克隆抗体的癌症的方法
公开(公告)号：WO2011054359A3
公开(公告)日：2011-10-06
申请号：PCT/DK2010050297
申请日：2010-11-05
申请人： UNIV COPENHAGEN , WANDALL HANS HEUGH , PEDERSEN JOHANNES WIRENFELDT VAD , BENNETT ERIC PAUL , CLAUSEN HENRIK , MANDEL ULLA
发明人： WANDALL HANS HEUGH , PEDERSEN JOHANNES WIRENFELDT VAD , BENNETT ERIC PAUL , CLAUSEN HENRIK , MANDEL ULLA
IPC分类号： G01N33/574 , A61P35/00 , C07K14/00 , C07K16/00
CPC分类号： G01N33/57484 , C07K14/00 , C07K16/00 , C07K16/3092 , C07K2317/732
摘要： The present inventors have demonstrated that circulating auto-antibodies to cancer antigens hold promise as specific and sensitive biomarkers for the early detection of cancer. The present invention thus relates to methods of detecting cancer in a sample, comprising utilising a glycopeptide bait derived from human mucins with different cancer-associated O-glycans. Detected antibodies were demonstrated as glycopeptide specific, and it could be discriminated between e.g. colorectal cancer patients and healthy individuals. The inventors have also developed monoclonal antibodies based on the identified glycopeptides epitope baits, and demonstrated differential expression of the relevant target antigens. The invention thus, in a lock and key-based manner includes both glycopeptides and antibody tools for early detection of cancer, as well as methods of using the same for in situ visualisation and treatment of specific cancer types.
摘要翻译：本发明人已经证明，对癌症抗原的循环自身抗体作为用于癌症早期检测的特异性和敏感的生物标志物具有希望。因此，本发明涉及检测样品中癌症的方法，其包括利用来自人粘蛋白的糖肽诱饵与不同的癌相关O聚糖。检测到的抗体被证实为糖肽特异性，并且可以区分例如。结直肠癌患者和健康个体。本发明人还开发了基于鉴定的糖肽表位诱饵的单克隆抗体，并证明了相关靶抗原的差异表达。因此，本发明以锁和键为基础的方式包括用于癌症早期检测的糖肽和抗体工具，以及将其用于特定癌症类型的原位可视化和治疗的方法。

36. 发明申请

WO2007047687A3 COMPOSITIONS AND METHODS FOR PROLONGING SURVIVAL OF PLATELETS 审中-公开
标题翻译：组合物和方法用于促进板材的存活
公开(公告)号：WO2007047687A3
公开(公告)日：2007-06-28
申请号：PCT/US2006040579
申请日：2006-10-16
申请人： ZYMEQUEST INC , ROSIELLO KEITH M , CLAUSEN HENRIK , WANDALL HANS H
发明人： ROSIELLO KEITH M , CLAUSEN HENRIK , WANDALL HANS H
IPC分类号： A61K38/47 , A61K31/7072
CPC分类号： A01N1/0221 , A61K31/70 , A61K35/19 , G01N33/86 , G01N2800/222 , G01N2800/224
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予该药物组合物以介导止血的方法。

37. 发明申请

WO2004042075A3 INACTIVATED GA1 - NAC - TRANSFERASES, METHODS FOR INHIBITORS OF SUCH TRANSFERASES AND THEIR USE 审中-公开
标题翻译：不活化的GA1 - NAC-转移，这种转移的抑制剂的方法及其使用
公开(公告)号：WO2004042075A3
公开(公告)日：2004-09-10
申请号：PCT/DK0300763
申请日：2003-11-07
申请人： GLYCOZYM APS , CLAUSEN HENRIK , BENNETT ERIC PAUL
发明人： CLAUSEN HENRIK , BENNETT ERIC PAUL
IPC分类号： A61K38/00 , A61K38/14 , A61K38/17 , C07K14/47 , C12N9/10 , C12Q1/48
CPC分类号： C07K14/4726 , A61K38/14 , A61K38/1709 , C12N9/1051 , C12Q1/48 , G01N2500/00 , G01N2500/04 , G01N2500/10
摘要： Novel methods for identification of inhibitors or modulators of binding activities mediated by lectin domains of polypeptide GaINAc-transferases are disclosed. Direct binding activity of GaINAc-transferase lectins has been demonstrated for the first time and methods to measure lectin mediated binding of isolated lectins or enzymes with lectin domains are disclosed. The present invention specifically discloses a novel selective inhibitor of polypeptide Ga1NAc-transferase lectin domains, which provides a major advancement in that this inhibitor and related inhibitors sharing common characteristics of activity bind lectin domains without serving as acceptor substrate for glycosyltransferases involved in synthesis of O-glycans. This inhibitor is represented by the ß-anomeric configuration of GaINAc-benzyl, Ga1NAcß-benzyl. Methods for inhibiting intracellular transport, cell surface expression, and secretion of mucins and 0-glycosylated glycoproteins without affecting 0-glycosylation processing are disclosed using the novel selective inhibitor identified.
摘要翻译：公开了用于鉴定由多肽GalNAc转移酶的凝集素结构域介导的结合活性的抑制剂或调节剂的新方法。首次证实了GalNAc转移酶凝集素的直接结合活性，并且公开了测定凝血素介导的分离的凝集素或酶与凝集素结构域的结合的方法。本发明具体公开了一种多肽Ga1NAc转移酶凝集素结构域的新型选择性抑制剂，其提供了主要进展，该抑制剂和相关抑制剂共享活性结合凝集素结构域的共同特征，而不用作参与合成O-糖蛋白的糖基转移酶的受体底物，聚糖。该抑制剂由GaNAc-苄基，Ga1NAcβ-苄基的β-端基异构构型表示。使用所鉴定的新型选择性抑制剂公开了抑制细胞内转运，细胞表面表达和粘蛋白和O-糖基化糖蛋白分泌而不影响O-糖基化加工的方法。

38. 发明申请

WO0185215A2 METHODS OF MODULATING FUNCTIONS OF POLYPEPTIDE GALNAC-TRANSFERASES AND OF SCREENING TEST SUBSTANCES TO FIND AGENTS HEREFOR, PHARMACEUTICAL COMPOSITIONS COMPRISING SUCH AGENTS AND THE USE OF SUCH AGENTS FOR PREPARING MEDICAMENTS 审中-公开
标题翻译：调查多肽GALNAC转移功能的方法和筛选试验物质，以查找其中的药剂，包含这些药剂的药物组合物和这些药剂用于制备药物的用途
公开(公告)号：WO0185215A2
公开(公告)日：2001-11-15
申请号：PCT/DK0100328
申请日：2001-05-10
申请人： CLAUSEN HENRIK , HASSAN HELLE , REIS CELSO ALBUQUERQUE , BENNETT ERIC PAUL
发明人： CLAUSEN HENRIK , HASSAN HELLE , REIS CELSO ALBUQUERQUE , BENNETT ERIC PAUL
IPC分类号： A61K38/00 , A61K38/14 , A61K38/17 , C12Q1/48 , A61K45/00
CPC分类号： C12Q1/48 , A61K38/005 , A61K38/14 , A61K38/1709 , G01N2333/91102 , G01N2500/00 , G01N2500/10
摘要： Attachment of O-glycans to proteins is controlled by a large family of homologous polypeptide GalNAc-transferases. Polypeptide GalNAc-transferases contain a C-terminal sequence with similarity to lectins. This invention discloses that the putative lectin domains of GalNAc-transferase isoforms, GalNAc-T4, -T7, -T2, and T3, are functional and recognize carbohydrates, glycopeptides, and peptides. These lectin domains have different binding specificities and modulate the functions of GalNAc-transferase isoforms differently. The lectin domains of GalNAc-T- and -T7 directs the glycopeptide specificities of these enzymes, while the lectin domains of GalNAc-T2 and -T3 directs broadening of donor substrate specificities to include UDP-Gal. Selective inhibitors of these functions that do not eliminate general catalytic activities are disclosed. Such inhibitors disclosed include free sugars, aryl-sugar derivatives, and glycopeptides. Inhibitors of GalNAc-transferase lectin domains are useful for altering the O-glycosylation capacity of cells, tissues, and organisms, and such agents may also interfere with other binding functions involved in intracellular sorting and secretion events.
摘要翻译： O-聚糖对蛋白质的附着由大量的同源多肽GalNAc转移酶家族控制。多肽GalNAc转移酶含有与凝集素相似的C-末端序列。本发明公开了GalNAc转移酶同工型，GalNAc-T4，-T7，-T2和T3的推定凝集素结构域是功能性的并识别碳水化合物，糖肽和肽。这些凝集素结构域具有不同的结合特异性，并且不同地调节GalNAc转移酶同工型的功能。 GalNAc-T和-T7的凝集素结构域指导这些酶的糖肽特异性，而GalNAc-T2和-T3的凝集素结构域则指导供体底物特异性的扩大以包括UDP-Gal。公开了不消除一般催化活性的这些功能的选择性抑制剂。所公开的抑制剂包括游离糖，芳基糖衍生物和糖肽。 GalNAc转移酶凝集素结构域的抑制剂可用于改变细胞，组织和生物体的O-糖基化能力，并且这些试剂也可能干扰参与细胞内分选和分泌事件的其他结合功能。

39. 发明申请

WO0114535A3 UDP-N-ACETYLGLUCOSAMINE: GALACTOSE- beta 1,3-N-ACETYLGALACTOSAMINE- alpha -R/(GlcNAc to GalNAc) beta 1,6-N-ACETYLGLUCOSAMINYLTRANSFERASE, C2GnT3 审中-公开
标题翻译： UDP-N-乙酰半胱氨酸：半乳糖-β-1,3-N-乙酰半乳糖胺-α-R /（GlcNAc-GalNAc）β1,6-N-乙酰葡糖胺转移酶，C2GnT3
公开(公告)号：WO0114535A3
公开(公告)日：2001-06-21
申请号：PCT/DK0000469
申请日：2000-08-24
申请人： SCHWIENTEK TILO , CLAUSEN HENRIK
发明人： SCHWIENTEK TILO , CLAUSEN HENRIK
IPC分类号： G01N33/53 , A61K31/7088 , A61K31/7105 , A61K38/00 , A61K38/45 , A61K39/395 , A61K45/00 , A61K48/00 , A61P5/00 , A61P31/18 , A61P35/00 , A61P35/02 , A61P35/04 , A61P43/00 , C07K16/40 , C12N1/21 , C12N5/10 , C12N9/10 , C12N15/09 , C12P19/00 , C12Q1/02 , C12Q1/48 , C12Q1/68 , C12R1/91
CPC分类号： C12N9/1051 , A61K38/00 , A61K48/00
摘要： A novel gene defining a novel human UDP-GlcNAc: Gal beta 1-3GAlNAc alpha beta 1, 6GlcNAc-transferase, termed C2GnT3, with unique enzymatic properties is disclosed. The invention discloses isolated DNA molecules and DNA constructs encoding C2GnT3, as well as cloning and expression vectors including such DNA. The enzyme 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 enzymatically active C2GnT3 protein or fusion protein thereof or by using cells stably transfected with a vector including DNA encoding an enzymatically active C2GnT3 protein. Methods are disclosed for the identification of agents with the ability to inhibit or stimulate the biological activity of C2GnT3.
摘要翻译：公开了定义具有独特酶性质的新型人类UDP-GlcNAc：Galβ1-3GAlNAcαβ1,6GlcNAc-转移酶（称为C2GnT3）的新基因。本发明公开了编码C2GnT3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。公开了酶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蛋白或其融合蛋白获得1,6-N-乙酰葡糖胺基糖基化糖，糖肽或糖蛋白或通过使用稳定转染了包括编码酶促活性C2GnT3蛋白的DNA的载体的细胞。公开了用于鉴定具有抑制或刺激C2GnT3的生物活性的能力的试剂的方法。

40. 发明申请

WO0034449A8 UDP-N- ACETYL GLUCOSAMINE: GALACTOSE- beta 1, 3-N- ACETYL GALACTOSAMINE- alpha -R/ N- ACETYL GLUCOSAMINE - beta 1, 3-N- ACETYL GALACTOSAMINE- alpha -R (GlcNAc TO GalNAc) beta 1,6-N- ACETYL GLUCOSAMINYL TRANSFERASE, C2/4GnT 审中-公开
标题翻译： UDP-N-乙酰葡萄糖苷：GALACTOSE-β1,3-N-乙酰谷氨酸胺-α-R / N-乙酰葡萄糖苷-β1,3-N-乙酰氨基糖苷-α-R（GlcNAc TO GalNAc）β1,6 -N-乙酰胆碱转移酶，C2 / 4GnT
公开(公告)号：WO0034449A8
公开(公告)日：2000-08-17
申请号：PCT/DK9900677
申请日：1999-12-03
申请人： CLAUSEN HENRIK , SCHWIENTEK TILO
发明人： CLAUSEN HENRIK , SCHWIENTEK TILO
IPC分类号： C12N15/09 , C12N1/15 , C12N1/19 , C12N1/21 , C12N5/10 , C12N9/10 , C12Q1/68
CPC分类号： C12N9/1051
摘要： A novel gene defining a novel human UDP-GlcNAc: Gal/Gl cNAc beta 1-3GalNAc alpha beta 1, 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 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 / Gl cNAcβ1-3GalNAcαβ1,6GlcNAc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，以及包含这种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获得1,6- N-乙酰葡糖胺基糖基化糖，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中分离DNA，通过PCR扩增C2 / 4GnT编码外显子并检测DNA序列变异的存在来鉴定C2 / 4GnT基因中DNA序列变异的方法。

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