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1. 发明授权

US08828939B2 Modified vitamin K dependent polypeptides 有权
标题翻译：改良的维生素K依赖多肽
公开(公告)号：US08828939B2
公开(公告)日：2014-09-09
申请号：US11632552
申请日：2005-08-10
申请人： Thomas Weimer , Stefan Schulte , Kay Hofmann , Hans-Peter Hauser
发明人： Thomas Weimer , Stefan Schulte , Kay Hofmann , Hans-Peter Hauser
IPC分类号： A61K38/36 , C07K14/745 , C12N15/62 , C12N9/64
CPC分类号： C12N15/62 , C12N9/6424
摘要： The present invention relates to modified cDNA sequences coding for vitamin K-dependent polypeptides, in particular human Factor VII, human Factor VIIa, human Factor IX and human protein C and their derivatives with improved stability and extended plasma half life, recombinant expression vectors containing such cDNA sequences, host cells transformed with such recombinant expression vectors, recombinant polypeptides and derivatives which do have biological activities of the unmodified wild type protein but having improved stability and processes for the manufacture of such recombinant proteins and their derivatives. The invention also covers a transfer vector for use in human gene therapy, which comprises such modified DNA sequences.
摘要翻译：本发明涉及编码维生素K依赖多肽，特别是人因子VII，人因子VIIa，人因子IX和人蛋白C及其衍生物的修饰cDNA序列，其具有改善的稳定性和延长的血浆半衰期，含有这样的重组表达载体 cDNA序列，用这种重组表达载体转化的宿主细胞，确实具有未修饰的野生型蛋白质的生物活性但具有改进的稳定性的生物活性的重组多肽和衍生物，以及制备这些重组蛋白及其衍生物的方法。本发明还涵盖用于人基因治疗的转移载体，其包含这种修饰的DNA序列。

2. 发明申请

US20130337532A1 THERAPEUTIC POLYPEPTIDES WITH INCREASED IN VIVO RECOVERY 审中-公开
标题翻译：治疗性多糖在体重恢复中增加
公开(公告)号：US20130337532A1
公开(公告)日：2013-12-19
申请号：US13921815
申请日：2013-06-19
申请人： Thomas Weimer , Hubert Metzner , Stefan Schulte , Wiegand Lang , Wilfried Wormsbacher
发明人： Thomas Weimer , Hubert Metzner , Stefan Schulte , Wiegand Lang , Wilfried Wormsbacher
IPC分类号： C12N9/64
CPC分类号： C12N9/644 , A61K47/62 , A61K47/643 , C07K2319/31 , C12N9/14 , C12N9/6424 , C12N9/6437
摘要： The present invention relates to the field of modified therapeutic polypeptides with increased in vivo recovery compared to their non-modified parent polypeptide. For example, the invention relates to fusions of therapeutic polypeptides with recovery enhancing polypeptides connected directly or optionally connected by a linker peptide.
摘要翻译：本发明涉及与其未修饰的亲本多肽相比具有增加的体内恢复的修饰的治疗性多肽的领域。例如，本发明涉及治疗性多肽与通过连接肽直接连接或任选连接的恢复增强多肽的融合。

3. 发明授权

US07827820B2 Thermodynamic machine and method for absorbing heat 失效
标题翻译：热力机及吸热方法
公开(公告)号：US07827820B2
公开(公告)日：2010-11-09
申请号：US10557423
申请日：2004-05-21
申请人： Thomas Weimer , Michael Hackner , Hans Hasse , Norbert Stroh , Eckehart Walitza
发明人： Thomas Weimer , Michael Hackner , Hans Hasse , Norbert Stroh , Eckehart Walitza
IPC分类号： F25B15/00
CPC分类号： F25B15/14 , Y02A30/277 , Y02B30/62
摘要： A thermodynamic machine for the absorption and emission of heat at different temperatures has at least one thermodynamic device with at least one membrane separating a gas phase and a liquid phase provided for transport of heat, wherein the at least one membrane is permeable for at least one component contained in the gas and liquid phases. The at least one membrane is a porous membrane or a solution diffusion membrane or a modification of the porous membrane or a modification of the solution diffusion membrane.
摘要翻译：用于在不同温度下吸收和释放热量的热力学机构具有至少一个热力学装置，至少一个膜分离用于传输热量的气相和液相，其中所述至少一个膜可透过至少一个气相和液相中所含的组分。至少一个膜是多孔膜或溶液扩散膜或多孔膜的改性或溶液扩散膜的改性。

4. 发明申请

US20090175828A1 Coagulation Factor X Polypeptides With Modified Activation Properties 有权
标题翻译：凝血因子X多肽具有改良的激活特性
公开(公告)号：US20090175828A1
公开(公告)日：2009-07-09
申请号：US12224182
申请日：2007-02-19
申请人： Stefan Schulte , Hans-Peter Hauser , Uwe Kalina , Thomas Weimer
发明人： Stefan Schulte , Hans-Peter Hauser , Uwe Kalina , Thomas Weimer
IPC分类号： A61K38/36 , C07K14/745 , C12N15/12 , C12N15/63 , C12N5/10 , C12P21/00 , A61P7/02
CPC分类号： C12N9/647 , A61K38/012 , A61K38/36 , C12N9/6432 , C12Y304/21006
摘要： The present invention relates to modified cDNA sequences coding for factor X polypeptides, in particular human factor X and its derivatives which can bypass the need for either factor VIIIa/factor IXa or factor VIIa/tissue factor for activation. The invention relates further to recombinant expression vectors containing such modified cDNA sequences, host cells transformed with such recombinant expression vectors, recombinant polypeptides and derivatives which do have biological activities of the unmodified wild type protein but having altered activation properties, and processes for the manufacture of such recombinant proteins and their derivatives. The invention also covers a transfer vector for use in human gene therapy, which comprises such modified DNA sequences.
摘要翻译：本发明涉及编码因子X多肽，特别是人因子X及其衍生物的修饰的cDNA序列，其可以绕过对因子VIIIa /因子IXa或因子VIIa /组织因子进行活化的需要。本发明还涉及含有这种修饰的cDNA序列的重组表达载体，用这种重组表达载体转化的宿主细胞，确实具有未修饰的野生型蛋白的生物活性但具有改变的活化性质的重组多肽和衍生物，以及制备这些重组蛋白及其衍生物。本发明还涵盖用于人基因治疗的转移载体，其包含这种修饰的DNA序列。

5. 发明申请

US20090053185A1 Coagulation factor x polypeptides with modified activation properties 有权
标题翻译：凝血因子x多肽具有修饰的活化特性
公开(公告)号：US20090053185A1
公开(公告)日：2009-02-26
申请号：US11921399
申请日：2006-05-30
申请人： Stefan Schulte , Hans-Peter Hauser , Uwe Kalina , Thomas Weimer
发明人： Stefan Schulte , Hans-Peter Hauser , Uwe Kalina , Thomas Weimer
IPC分类号： A61K48/00 , C07K2/00 , C07H21/04 , C12N15/63 , C12N5/00 , C12P21/06 , A61K38/00 , A61K31/7088
CPC分类号： C12N9/6432 , C12Y304/21006
摘要： The present invention relates to modified cDNA sequences coding for human Factor X and their derivatives with improved stability and modified activation sequences, recombinant expression vectors containing such cDNA sequences, and host cells transformed with such recombinant expression vectors. The invention also relates to recombinant factor X polypeptides and derivatives which have biological activities of the unmodified wild type protein but with improved stability and processes for the manufacture of such recombinant proteins and their derivatives. The invention also covers a transfer vector for use in human gene therapy, which comprises such modified DNA.
摘要翻译：本发明涉及编码具有改善的稳定性和修饰的活化序列的人因子X及其衍生物的修饰的cDNA序列，含有此类cDNA序列的重组表达载体和用这些重组表达载体转化的宿主细胞。本发明还涉及具有未修饰的野生型蛋白的生物活性但具有改进的稳定性的重组因子X多肽和衍生物，以及用于制备这些重组蛋白及其衍生物的方法。本发明还涵盖用于人基因治疗的转移载体，其包含这种修饰的DNA。

6. 发明授权

US06831167B2 Mutants of the factor VII-activating protease and detection methods using specific antibodies 失效
标题翻译：因子VII活化蛋白酶的突变体和使用特异性抗体的检测方法
公开(公告)号：US06831167B2
公开(公告)日：2004-12-14
申请号：US09912559
申请日：2001-07-26
申请人： Juergen Roemisch , Hans-Arnold Stoehr , Annette Feussner , Wiegand Lang , Thomas Weimer , Margret Becker , Claudia Nerlich , Gudrun Muth-Naumann
发明人： Juergen Roemisch , Hans-Arnold Stoehr , Annette Feussner , Wiegand Lang , Thomas Weimer , Margret Becker , Claudia Nerlich , Gudrun Muth-Naumann
IPC分类号： C07H2104
CPC分类号： C12N9/647 , A61K38/00 , C07K16/40 , C12N9/6424 , G01N33/86 , G01N2333/96463
摘要： Mutants of the DNA sequence coding for the protease (FSAP) which activates blood clotting factor VII and single-chain plasminogen activators, the mutants comprising a G/C base exchange at nucleotide position 1177 and/or a G/A base exchange at nucleotide position 1601, are described. The corresponding protease has a Glu/Gln exchange at amino acid position 393 and/or a Gly/Glu exchange at amino acid position 534. Diagnostic methods which are used for detecting FSAP in body fluids or tissue cells and also for identifying patients with genetic heterozygous or homozygous FSAP expression are also described. In addition, antibodies against FSAP and its mutants are disclosed and diagnostic methods which can be used to detect antibodies against FSAP and its mutants are specified.
摘要翻译：编码激活血液凝固因子VII和单链纤溶酶原激活物的蛋白酶（FSAP）的DNA序列的突变体，在核苷酸位置1177处包含G / C碱基交换的突变体和/或核苷酸位置处的G / A碱基交换 1601。相应的蛋白酶在氨基酸位置393处具有Glu / Gln交换和/或氨基酸位置534处的Gly / Glu交换。用于检测体液或组织细胞中的FSAP的诊断方法以及用于鉴定具有遗传杂合的患者或纯合的FSAP表达也被描述。另外，公开了针对FSAP及其突变体的抗体，并且可以用于检测针对FSAP及其突变体的抗体的诊断方法。

7. 发明授权

US06183999B2 Procedure for the detection of high virus concentrations in blood plasma and/or blood serum by means of the polymerase chain reaction 有权
标题翻译：通过聚合酶链反应检测血浆和/或血清中高病毒浓度的方法
公开(公告)号：US06183999B2
公开(公告)日：2001-02-06
申请号：US09198243
申请日：1998-11-24
申请人： Thomas Weimer , Albrecht Groener
发明人： Thomas Weimer , Albrecht Groener
IPC分类号： C12P1934
CPC分类号： C12Q1/701
摘要： A procedure for the detection of high virus concentrations in blood plasma and/or blood serum by means of the polymerase chain reaction (PCR) is described, in which the sensitivity of the PCR is restricted by the use of suboptimal nucleic acid extraction, amplification or detection conditions. This procedure is suitable, for example, for the detection of parvovirus DNA in plasma or serum, it being possible to adjust the sensitivity of the PCR such that the parvovirus DNA is only detected in samples whose DNA content is greater than 106 to 107 genome equivalents/ml. The detection of the parvovirus DNA amplification carried out is carried out in the sample by measurements of the fluorescence.
摘要翻译：描述了通过聚合酶链式反应（PCR）检测血浆和/或血清中高病毒浓度的方法，其中PCR的灵敏度通过使用次最佳核酸提取，扩增或检测条件。该方法例如用于检测血浆或血清中的细小病毒DNA，可以调节PCR的灵敏度，使得仅在DNA含量大于106至107个基因组当量的样品中检测到细小病毒DNA / ml。通过荧光测量在样品中进行细小病毒DNA扩增的检测。

8. 发明授权

US07863009B2 Mutants of the factor VII-activating protease and detection methods using specific antibodies 有权
标题翻译：因子VII活化蛋白酶的突变体和使用特异性抗体的检测方法
公开(公告)号：US07863009B2
公开(公告)日：2011-01-04
申请号：US12232350
申请日：2008-09-16
申请人： Juergen Roemisch , Hans-Arnold Stoehr , Annette Feussner , Wiegand Lang , Thomas Weimer , Margret Becker , Claudia Nerlich , Gudrun Muth-Naumann , Bernd Knoblauch
发明人： Juergen Roemisch , Hans-Arnold Stoehr , Annette Feussner , Wiegand Lang , Thomas Weimer , Margret Becker , Claudia Nerlich , Gudrun Muth-Naumann , Bernd Knoblauch
IPC分类号： G01N33/53
CPC分类号： C12N9/647 , A61K38/00 , C07K16/40 , C12N9/6424 , G01N33/86 , G01N2333/96463
摘要： Mutants of the DNA sequence coding for the protease (FSAP) which activates blood clotting factor VII and single-chain plasminogen activators, the mutants comprising a G/C base exchange at nucleotide position 1177 and/or a G/A base exchange at nucleotide position 1601, are described. The corresponding protease has a Glu/Gln exchange at amino acid position 393 and/or a Gly/Glu exchange at amino acid position 534. Diagnostic methods which are used for detecting FSAP in body fluids or tissue cells and also for identifying patients with genetic heterozygous or homozygous FSAP expression are also described. In addition, antibodies against FSAP and its mutants are disclosed and diagnostic methods which can be used to detect antibodies against FSAP and its mutants are specified.
摘要翻译：编码激活血液凝固因子VII和单链纤溶酶原激活物的蛋白酶（FSAP）的DNA序列的突变体，在核苷酸位置1177处包含G / C碱基交换的突变体和/或核苷酸位置处的G / A碱基交换 1601。相应的蛋白酶在氨基酸位置393处具有Glu / Gln交换和/或氨基酸位置534处的Gly / Glu交换。用于检测体液或组织细胞中的FSAP的诊断方法以及用于鉴定具有遗传杂合的患者或纯合的FSAP表达也被描述。另外，公开了针对FSAP及其突变体的抗体，并且可以用于检测针对FSAP及其突变体的抗体的诊断方法。

9. 发明申请

US20100120664A1 MODIFIED COAGULATION FACTORS WITH PROLONGED IN VIVO HALF-LIFE 有权
标题翻译：改良的凝血因子与生殖健康生活息息相关
公开(公告)号：US20100120664A1
公开(公告)日：2010-05-13
申请号：US12520840
申请日：2007-12-21
申请人： Stefan Schulte , Thomas Weimer , Hubert Metzner
发明人： Stefan Schulte , Thomas Weimer , Hubert Metzner
IPC分类号： A61K38/16 , C07K14/745 , C07K14/755 , C07H21/00 , C12N15/74 , C12N5/10 , C12P21/00 , A61P7/04
CPC分类号： C07K14/755 , C07K14/745 , C07K14/765 , C07K16/18 , C07K2319/31
摘要： The present invention relates to nucleic acid sequences coding for modified coagulation factors, preferably coagulation factor VIII, and their derivatives; recombinant expression vectors containing such nucleic acid sequences; host cells transformed with such recombinant expression vectors; and recombinant polypeptides and derivatives coded for by said nucleic acid sequences, whereby said recombinant polypeptides and derivatives have biological activities and prolonged in vivo half-lives compared to the unmodified wild-type proteins. The invention also relates to corresponding sequences that result in improved in vitro stability. The present invention further relates to processes for the manufacture of such recombinant proteins and their derivatives. The invention also relates to a transfer vector for use in human gene therapy, which comprises such nucleic acid sequences.
摘要翻译：本发明涉及编码改性凝血因子，优选凝血因子VIII及其衍生物的核酸序列; 含有该核酸序列的重组表达载体; 用这些重组表达载体转化的宿主细胞; 和由所述核酸序列编码的重组多肽和衍生物，其中与未修饰的野生型蛋白相比，所述重组多肽和衍生物具有生物学活性和延长的体内半衰期。本发明还涉及导致体外稳定性改善的相应序列。本发明还涉及制备这些重组蛋白及其衍生物的方法。本发明还涉及用于人基因治疗的转移载体，其包含这样的核酸序列。

10. 发明申请

US20080274969A1 Albumin-Fused Kunitz Domain Peptides 审中-公开
标题翻译：白蛋白融合Kunitz结构域肽
公开(公告)号：US20080274969A1
公开(公告)日：2008-11-06
申请号：US12114477
申请日：2008-05-02
申请人： Hans-Peter Hauser , Thomas Weimer , Val Romberg , Scott M. Kee , Darrell Sleep , Robert Charles Ladner , Arthur C. Ley
发明人： Hans-Peter Hauser , Thomas Weimer , Val Romberg , Scott M. Kee , Darrell Sleep , Robert Charles Ladner , Arthur C. Ley
IPC分类号： A61K38/38 , C07K14/76 , C07H21/00 , C12N15/00 , C12N5/00 , C12P21/04
CPC分类号： C12N15/62 , C07K2319/31
摘要： The invention relates to proteins comprising serine protease inhibiting peptides, such as Kunitz domain peptides (including, but not limited to, fragments and variants thereof) fused to albumin, or fragments or variants thereof. These fusion proteins are herein collectively referred to as “albumin fusion proteins of the invention.” These fusion proteins exhibit extended shelf-life and/or extended or therapeutic activity in solution. The invention encompasses therapeutic albumin fusion proteins, compositions, pharmaceutical compositions, formulations and kits. The invention also encompasses nucleic acid molecules and vectors encoding the albumin fusion proteins of the invention, host cells transformed with these nucleic acids and vectors, and methods of making the albumin fusion proteins of the invention using these nucleic acids, vectors, and/or host cells. The invention also relates to compositions and methods for inhibiting neutrophil elastase, kallikrein, and plasmin. The invention further relates to compositions and methods for treating cystic fibrosis and cancer.
摘要翻译：本发明涉及包含丝氨酸蛋白酶抑制肽的蛋白质，例如与白蛋白或其片段或变体融合的Kunitz结构域肽（包括但不限于其片段和变体）。这些融合蛋白在本文中统称为“本发明的白蛋白融合蛋白”。这些融合蛋白在溶液中表现出延长的保质期和/或延长或治疗活性。本发明包括治疗性白蛋白融合蛋白，组合物，药物组合物，制剂和试剂盒。本发明还包括编码本发明的白蛋白融合蛋白，用这些核酸和载体转化的宿主细胞的核酸分子和载体，以及使用这些核酸，载体和/或宿主制备本发明的白蛋白融合蛋白的方法细胞。本发明还涉及抑制嗜中性粒细胞弹性蛋白酶，激肽释放酶和纤溶酶的组合物和方法。本发明还涉及治疗囊性纤维化和癌症的组合物和方法。

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