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11. 发明授权

US5409699A Compositions containing glycosylated molecules having human tissue type plasminogen activator enzymatic activity 失效
标题翻译：含有具有人组织型纤溶酶原激活物酶活性的糖基化分子的组合物
公开(公告)号：US5409699A
公开(公告)日：1995-04-25
申请号：US741401
申请日：1991-07-19
申请人： Ulrich Kohnert , Rainer Rudolph
发明人： Ulrich Kohnert , Rainer Rudolph
IPC分类号： A61K38/46 , A61K38/49 , A61K47/12 , A61K47/16 , A61K47/18 , A61K47/20 , A61K47/22 , A61K47/26 , A61P7/02 , A61K37/547 , C12N9/96 , A61K37/48 , A61K37/62
CPC分类号： A61K47/18 , A61K38/49 , A61K47/12 , A61K47/183 , A61K47/20 , A61K47/22 , A61K47/26 , A61K9/0019
摘要： The invention is a pharmaceutical composition containing a glycosylated protein having human tissue type plasminogen activator activity of at least 1.4 MU/ml, citrate, and at least one of a number of various compounds. The composition has a pH ranging from 4.5 to 9.
摘要翻译： PCT No.PCT / EP90 / 02252 Sec。 371日期1991年7月19日 102（e）日期1991年7月19日PCT 1990年12月19日PCT PCT。公开号WO91 / 08767 日期：1991年6月27日。本发明是一种药物组合物，其含有具有至少1.4MU / ml，柠檬酸盐和多种各种化合物中的至少一种的人组织型纤溶酶原激活剂活性的糖基化蛋白质。该组合物的pH为4.5至9。

12. 发明授权

US09150641B2 Sequence dependent aggregation 有权
标题翻译：序列依赖聚集
公开(公告)号：US09150641B2
公开(公告)日：2015-10-06
申请号：US13515428
申请日：2010-12-17
申请人： Hubert Kettenberger , Stefan Klostermann , Ulrich Kohnert , Sebastian Neumann
发明人： Hubert Kettenberger , Stefan Klostermann , Ulrich Kohnert , Sebastian Neumann
IPC分类号： C12P21/02 , C07K1/00 , C07K16/00 , C07K16/28
CPC分类号： C07K16/2866 , C07K16/00 , C07K16/2875 , C07K16/461 , C07K2317/24 , C07K2317/567
摘要： Herein is reported a method for reducing the aggregation of an immunoglobulin in solution comprising the steps of i) comparing the amino acid sequence of the fourth framework region of the heavy chain of an antibody with a reference or germline sequence and determining whether one or more threonine residues and/or serine residues have been replaced by a different amino acid residue, and ii) modifying the amino acid sequence of the immunoglobulin by reverting the exchanged threonine residues and/or serine residues back to threonine or serine of the reference or germline sequence and thereby reducing the aggregation of an immunoglobulin in solution.
摘要翻译：本文报道了用于减少溶液中免疫球蛋白聚集的方法，包括以下步骤：i）比较抗体重链的第四框架区的氨基酸序列与参照或种系序列，并确定一个或多个苏氨酸残基和/或丝氨酸残基已经被不同的氨基酸残基替代，和ii）通过将交换的苏氨酸残基和/或丝氨酸残基还原回参考或种系序列的苏氨酸或丝氨酸来修饰免疫球蛋白的氨基酸序列，以及从而减少溶液中免疫球蛋白的聚集。

13. 发明申请

US20060240062A1 Metal implant coated under reduced oxygen concentration with osteoinductive protein 失效
标题翻译：金属植入物在降低氧浓度下用骨诱导蛋白包被
公开(公告)号：US20060240062A1
公开(公告)日：2006-10-26
申请号：US10527047
申请日：2003-07-09
申请人： Klaus Hellerbrand , Nicola Beaucamp , Ulrich Kohnert
发明人： Klaus Hellerbrand , Nicola Beaucamp , Ulrich Kohnert
IPC分类号： A61F2/00
CPC分类号： A61L27/04 , A61C8/0012 , A61C8/0013 , A61F2/30767 , A61F2/32 , A61F2/38 , A61F2/3804 , A61F2/4202 , A61F2/4241 , A61F2/44 , A61F2310/00023 , A61F2310/00976 , A61L27/227 , Y10T428/31678
摘要： The present invention relates to a method for producing a device comprising the steps of (a) providing a solution comprising dissolved osteoinductive protein, (b) contacting the solution of the preceding step with a carrier containing a surface of metal or a metal alloy, (c) allowing coating of the surface of said carrier with said dissolved protein and (d) drying of the coated carrier obtained in step (c) wherein steps (b) to (d) are carried out under a reduced concentration of oxygen. The invention also encompasses a device obtainable by the method of the present invention. Moreover, the present invention relates to a pharmaceutical composition comprising the said device and to the use of the device for the preparation of a pharmaceutical composition to be used for an accelerated osseointegration and new bone formation. Finally, the present invention relates to a kit comprising the device of the present invention.
摘要翻译：本发明涉及一种用于制备器件的方法，包括以下步骤：（a）提供包含溶解的骨诱导蛋白的溶液，（b）使前述步骤的溶液与含有金属或金属合金表面的载体接触（ c）允许用所述溶解的蛋白质涂覆所述载体的表面，和（d）干燥步骤（c）中获得的涂布载体，其中步骤（b）至（d）在氧浓度降低的情况下进行。本发明还包括可通过本发明的方法获得的装置。此外，本发明涉及包含所述装置的药物组合物和用于制备用于加速骨整合和新骨形成的药物组合物的该装置的用途。最后，本发明涉及包含本发明装置的试剂盒。

14. 发明授权

US5747030A Pharmaceutical preparation containing plasminogen activators 失效
标题翻译：含有纤溶酶原激活剂的药物制剂
公开(公告)号：US5747030A
公开(公告)日：1998-05-05
申请号：US693226
申请日：1996-08-21
申请人： Ulrich Kohnert , Stephan Fischer , Hans-Jorg Markl , Heinrich Woog
发明人： Ulrich Kohnert , Stephan Fischer , Hans-Jorg Markl , Heinrich Woog
IPC分类号： C12N9/64 , A61K9/00 , A61K9/14 , A61K38/46 , A61K38/49 , A61K47/00 , A61K47/02 , A61K47/12 , A61K47/18 , A61K47/26 , A61P7/02 , A61K38/48 , A61K38/54
CPC分类号： A61K9/0019 , A61K38/49 , A61K47/183 , A61K47/02 , A61K47/26
摘要： The invention relates to pharmaceutical preparations containing plasminogen activators, sugars and tranexamic acid, in the form of a lyophilisate or an injection or infusion solution. In particular, the preparations contain a sugar, phosphate buffer, tranexamic acid as well as a surfactant and the liquid solutions preferably have a pH value of 5.5-6.5.
摘要翻译： PCT No.PCT / EP95 / 00596 371日期：1996年8月21日 102（e）日期1996年8月21日PCT提交1995年2月18日PCT公布。 WO95 / 22347 PCT出版物日期1995年8月24日本发明涉及含有纤溶酶原激活剂，糖和凝血酸的药物制剂，其为冻干物或注射液或输注溶液。特别地，制剂含有糖，磷酸盐缓冲液，凝血酸和表面活性剂，液体溶液的pH值优选为5.5-6.5。

15. 发明申请

US20130065277A1 SEQUENCE DEPENDENT AGGREGATION 有权
标题翻译：序列依赖性聚集
公开(公告)号：US20130065277A1
公开(公告)日：2013-03-14
申请号：US13515428
申请日：2010-12-17
申请人： Hubert Kettenberger , Stefan Klostermann , Ulrich Kohnert , Sebastian Neumann
发明人： Hubert Kettenberger , Stefan Klostermann , Ulrich Kohnert , Sebastian Neumann
IPC分类号： C12P21/02 , C07K1/00 , C07H1/00
CPC分类号： C07K16/2866 , C07K16/00 , C07K16/2875 , C07K16/461 , C07K2317/24 , C07K2317/567
摘要： Herein is reported a method for reducing the aggregation of an immunoglobulin in solution comprising the steps of i) comparing the amino acid sequence of the fourth framework region of the heavy chain of an antibody with a reference or germline sequence and determining whether one or more threonine residues and/or serine residues have been replaced by a different amino acid residue, and ii) modifying the amino acid sequence of the immunoglobulin by reverting the exchanged threonine residues and/or serine residues back to threonine or serine of the reference or germline sequence and thereby reducing the aggregation of an immunoglobulin in solution.
摘要翻译：本文报道了用于减少溶液中免疫球蛋白聚集的方法，包括以下步骤：i）比较抗体重链的第四框架区的氨基酸序列与参照或种系序列，并确定一个或多个苏氨酸残基和/或丝氨酸残基已经被不同的氨基酸残基替代，和ii）通过将交换的苏氨酸残基和/或丝氨酸残基还原回参考或种系序列的苏氨酸或丝氨酸来修饰免疫球蛋白的氨基酸序列，以及从而减少溶液中免疫球蛋白的聚集。

16. 发明申请

US20060088565A1 Device having osteoinductive and osteoconductive properties 失效
标题翻译：具有骨诱导和骨传导性能的装置
公开(公告)号：US20060088565A1
公开(公告)日：2006-04-27
申请号：US10496399
申请日：2002-03-27
申请人： Ulrich Kohnert , Sylke Pohling , Klaus Hellerbrand , Peter Happersberger
发明人： Ulrich Kohnert , Sylke Pohling , Klaus Hellerbrand , Peter Happersberger
IPC分类号： A61K38/17 , A61K8/96 , A61K31/7012
CPC分类号： A61L27/227 , A61L24/02 , A61L24/108 , A61L27/12 , A61L27/34
摘要： The present invention relates to a device having osteoinductive and osteoconductive properties in vivo comprising a carrier containing calcium phosphate and an osteoinductive protein, wherein said carrier is homogenously coated with said protein. Moreover, the present invention relates to a method for the production of a device having osteoinductive and osteoconductive properties in vivo. The invention encompasses a pharmaceutical composition comprising the device of the invention or a device which is obtainable by the method of the invention and relates to the use of said device for the preparation of a pharmaceutical composition to be used for bone augmentation, for treating bone defects, for treating degenerative and traumatic disc disease, for treating bone dehiscence or to be used for sinus floor elevation. Finally, the invention relates to a kit comprising the device of the invention or a device which is obtainable by the method of the invention.
摘要翻译：本发明涉及一种在体内具有骨诱导和骨传导性质的装置，其包含含有磷酸钙和骨诱导蛋白的载体，其中所述载体均匀地涂覆有所述蛋白质。此外，本发明涉及在体内制造具有骨诱导性和骨传导性的装置的方法。本发明包括药物组合物，其包含本发明的装置或可通过本发明的方法获得的装置，并且涉及所述装置用于制备用于骨增大的药物组合物用于治疗骨缺损的用途用于治疗退行性和创伤性椎间盘疾病，用于治疗骨开裂或用于窦底抬高。最后，本发明涉及包含本发明的装置或可通过本发明的方法获得的装置的试剂盒。

17. 发明授权

US5973118A Mutant of the Erythrina caffra type inhibitor and the use of the said mutant for purifying serine proteases 失效
标题翻译： Erythrina caffra型抑制剂的突变体和所述突变体用于纯化丝氨酸蛋白酶的用途
公开(公告)号：US5973118A
公开(公告)日：1999-10-26
申请号：US943814
申请日：1997-10-03
申请人： Ulrich Kohnert , Anne Stern , Manfred Wozny , Stephan Fischer
发明人： Ulrich Kohnert , Anne Stern , Manfred Wozny , Stephan Fischer
IPC分类号： C12N15/09 , C07K1/22 , C07K14/81 , C12N1/21 , C12N9/64 , C12N9/72 , C12N9/99 , C12N15/29 , C12P21/02 , C12R1/19 , C07K1/00 , A61K35/78 , A61K38/00
CPC分类号： C12N9/6459 , C07K14/8114 , C12Y304/21069
摘要： A polypeptide which has the activity of an inhibitor DE-3 from Erythrina caffra and which reversibly and selectively binds serine proteases from a protein mixture is obtainable by culturing prokaryotic or eukaryotic host cells which have been transformed or transfected with a nucleic acid that codes for the said polypeptide in a manner that allows the host cells to express the said polypeptide under suitable nutrient conditions and isolating the said polypeptide, wherein the polypeptide has an amino acid sequence which is functionally analogous to SEQ ID NO:2, has a partial region that is more than 85% homologous to the region of amino acids 39-139 of this sequence, has two disulfide bridges and begins N-terminally with SEQ ID NO:4 or with a SEQ ID NO:4 extended N-terminally by methionine and has a binding capacity for tissue plasminogen activators of 1.25 MU/ml and more and is particularly suitable for purifying plasminogen activators such as tissue plasminogen activators (t-PA and derivatives).
摘要翻译：通过培养原核或真核宿主细胞获得具有来自艾瑞氏菌（Erythrina caffra）的抑制剂DE-3并且可逆地和选择性地结合蛋白质混合物的丝氨酸蛋白酶的多肽，所述原核或真核宿主细胞已经用编码所述多肽以允许宿主细胞在合适的营养条件下表达所述多肽并分离所述多肽的方式，其中所述多肽具有功能上类似于SEQ ID NO：2的氨基酸序列，其部分区域是与该序列的氨基酸39-139的区域同源超过85％具有两个二硫键，并与SEQ ID NO：4进行N-末端或与蛋氨酸N-末端扩增的SEQ ID NO：4，并具有组织纤溶酶原激活剂的结合能力为1.25 MU / ml以上，特别适用于纯化纤溶酶原激活剂如组织纤溶酶原激活剂（t-PA和de rivatives）。

18. 发明授权

US5366730A Stabilized compositions having human tissue type plasminogen activator enzymatic activity 失效
标题翻译：具有人组织型纤溶酶原激活物酶活性的稳定组合物
公开(公告)号：US5366730A
公开(公告)日：1994-11-22
申请号：US43619
申请日：1993-04-06
申请人： Ulrich Kohnert , Rainer Rudolph
发明人： Ulrich Kohnert , Rainer Rudolph
IPC分类号： A61K38/49 , A61K47/12 , A61K47/18 , A61K47/20 , A61K47/22 , A61K37/547 , A61K37/48 , A61K37/553 , C12N9/50
CPC分类号： A61K38/49 , A61K47/12 , A61K47/18 , A61K47/183 , A61K47/20 , A61K47/22 , A61K9/0019
摘要： Pharmaceutical preparation of a protein with t-PA activity with an enzymatic activity of at least 0.25 MU/ml. and a pH value of 4.5 to 9 which contains a substance of the group citric acid, ascorbic acid, 2-oxoglutaric acid, fumaric acid, Tris and EDTA in a concentration of at least 0.2 mole/l., as well as a medicament based on a protein with t-PA activity and processes for its preparation.
摘要翻译：具有至少0.25MU / ml的酶活性的具有t-PA活性的蛋白质的药物制备。并且pH值为4.5至9，其含有浓度为至少0.2摩尔/升的柠檬酸，抗坏血酸，2-氧戊二酸，富马酸，Tris和EDTA的物质以及药物基对具有t-PA活性的蛋白质及其制备方法。

19. 发明授权

US5352453A Compositions containing non-glycosylated human tissue type plasminogen activator 失效
标题翻译：含有非糖基化的人类组织型纤溶酶原激活物的组合物
公开(公告)号：US5352453A
公开(公告)日：1994-10-04
申请号：US741483
申请日：1991-08-06
申请人： Ulrich Kohnert , Rainer Rudolph
发明人： Ulrich Kohnert , Rainer Rudolph
IPC分类号： A61K38/46 , A61K38/49 , A61K47/12 , A61K47/16 , A61K47/18 , A61K47/20 , A61K47/22 , A61K47/26 , A61K47/42 , A61P7/02 , A01K37/48 , C12N9/96 , A01K37/547 , A01K37/62
CPC分类号： A61K47/12 , A61K38/49 , A61K47/18 , A61K47/183 , A61K47/22 , A61K47/26 , A61K9/0019
摘要： Pharmaceutical compositions containing non-glycosylated human tissue type plasminogen activator (t-PA) having enzymatic activity of at least 0.1 MU/ml are disclosed. The compositions have a pH of from 4.5 to 6, contain citrate, and at least one other compound.
摘要翻译：公开了含有至少0.1MU / ml的酶活性的非糖基化的人组织型纤溶酶原激活剂（t-PA）的药物组合物。组合物的pH为4.5至6，含有柠檬酸盐和至少一种其它化合物。

20. 发明授权

US5352452A Stabilized compositions containing non-glysylated human tissue type plasminogen activator derivative K2P pro 失效
标题翻译：含有非糖基化的人组织型纤溶酶原激活物衍生物K2P pro的稳定组合物
公开(公告)号：US5352452A
公开(公告)日：1994-10-04
申请号：US730938
申请日：1991-08-02
申请人： Ulrich Kohnert , Rainer Rudolph
发明人： Ulrich Kohnert , Rainer Rudolph
IPC分类号： A61K9/08 , A61K38/46 , A61K38/49 , A61K47/00 , A61K47/06 , A61K47/12 , A61K47/16 , A61K47/18 , A61K47/20 , A61K47/22 , A61K47/26 , A61P7/02 , A61K37/48 , A61K37/547 , A61K37/62 , C12N9/96
CPC分类号： A61K47/22 , A61K38/49 , A61K47/12 , A61K47/18 , A61K47/183 , A61K47/26 , A61K9/0019
摘要： Stabilized compositions containing a non-glycosylated human tissue type plasminogen activator derivative are disclosed. The derivative is referred to as K2P pro. The composition has enzymatic activity of at least 1.1 mU/ml, a pH of from 4.5 to 6.5, and contains citrate as well as at least one of a variety of different compounds.
摘要翻译： PCT No.PCT / EP90 / 02250 Sec。 371日期1991年8月2日 102（e）日期1991年8月2日PCT 1990年12月19日PCT PCT。公开号WO91 / 08765 日期：1991年6月27日。公开了含有非糖基化的人组织型纤溶酶原激活剂衍生物的稳定组合物。衍生物称为K2P亲。该组合物的酶活性至少为1.1mU / ml，pH为4.5至6.5，并且含有柠檬酸盐以及多种不同化合物中的至少一种。

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