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1. 发明授权

US10363323B2 Hydrophobic modified peptides for liver specific diagnosis 有权
公开(公告)号：US10363323B2
公开(公告)日：2019-07-30
申请号：US13984715
申请日：2012-02-10
申请人： Walter Mier , Stephan Urban , Stefan Mehrle , Uwe Haberkorn , Thomas Müller , Vasileios Askoxylakis
发明人： Walter Mier , Stephan Urban , Stefan Mehrle , Uwe Haberkorn , Thomas Müller , Vasileios Askoxylakis
IPC分类号： A61K51/08 , A61K38/00 , A61K49/00 , A61K49/08 , A61K49/14 , C07K14/005 , C12N7/00
摘要： The present invention relates to hydrophobic modified peptides for the specific delivery of labels to the liver, preferably to hepatocytes, in vitro as well as in vivo. The present invention relates to pharmaceutical compositions comprising said hydrophobic modified peptide(s) and the label(s) to be specifically delivered to the liver. The present invention furthermore relates to the diagnostic use of the inventive hydrophobic modified peptides as well as to a method for the diagnosis of liver diseases or disorders.

2. 发明申请

US20140038886A1 HYDROPHOBIC MODIFIED PEPTIDES AND THEIR USE FOR LIVER SPECIFIC TARGETING 审中-公开
标题翻译：疏水性改性肽及其用于肝脏特异性靶向
公开(公告)号：US20140038886A1
公开(公告)日：2014-02-06
申请号：US13984694
申请日：2012-02-10
申请人： Walter Mier , Stephan Urban , Stefan Mehrle , Uwe Haberkorn
发明人： Walter Mier , Stephan Urban , Stefan Mehrle , Uwe Haberkorn
IPC分类号： C07K7/08 , A61K47/48 , C07K14/00
摘要： The present invention relates to hydrophobic modified peptides for the specific delivery of compounds to the liver, preferably to hepatocytes, in vitro as well as in vivo. The present invention relates to pharmaceutical compositions comprising said hydrophobic modified peptide(s) and the compound(s) to be specifically delivered to the liver. The present invention furthermore relates to the use of the inventive hydrophobic modified peptides as well as to a method for the prevention and/or treatment of liver diseases or disorders.
摘要翻译：本发明涉及用于在体外和体内将化合物特异性递送至肝脏，优选肝细胞的疏水性修饰肽。本发明涉及包含所述疏水性修饰肽和要特异性递送至肝脏的化合物的药物组合物。本发明还涉及本发明的疏水性修饰肽的用途以及预防和/或治疗肝脏疾病或病症的方法。

3. 发明授权

US10513539B2 Hydrophobic modified peptides and their use for liver specific targeting 有权
公开(公告)号：US10513539B2
公开(公告)日：2019-12-24
申请号：US13984694
申请日：2012-02-10
申请人： Walter Mier , Stephan Urban , Stefan Mehrle , Uwe Haberkorn
发明人： Walter Mier , Stephan Urban , Stefan Mehrle , Uwe Haberkorn
IPC分类号： C07K7/08 , A61K51/04 , A61K51/08 , C07K14/00 , A61K47/54 , A61K47/64
摘要： The present invention relates to hydrophobic modified peptides for the specific delivery of compounds to the liver, preferably to hepatocytes, in vitro as well as in vivo. The present invention relates to pharmaceutical compositions comprising said hydrophobic modified peptide(s) and the compound(s) to be specifically delivered to the liver. The present invention furthermore relates to the use of the inventive hydrophobic modified peptides as well as to a method for the prevention and/or treatment of liver diseases or disorders.

4. 发明授权

US09868768B2 Hydrophobic modified pres-derived peptides of hepatitis B virus (HBV) and their use as vehicles for the specific delivery of compounds to the liver 有权
公开(公告)号：US09868768B2
公开(公告)日：2018-01-16
申请号：US12864197
申请日：2009-01-26
申请人： Walter Mier , Uwe Haberkorn , Stephan Urban
发明人： Walter Mier , Uwe Haberkorn , Stephan Urban
IPC分类号： A61K31/7052 , C12N15/63 , G01N33/53 , C07K14/005 , A61K38/16 , A61K39/00
CPC分类号： C07K14/005 , A61K38/162 , A61K2039/6075 , C07K2319/033 , C12N2730/10122 , C12N2810/6036 , Y02A50/41 , Y02A50/412 , Y02A50/423 , Y02A50/463
摘要： The present invention relates to hydrophobic modified preS-derived peptides of hepatitis B virus (HBV) which are versatile vehicles for the specific delivery of compounds to the liver, preferably to hepatocytes, in vitro as well as in vivo. Any kind of compound, but in particular drugs, such as interferons, viral reverse transcriptase inhibitors or core assembly inhibitors, and/or labels can be specifically targeted to the liver and so be enriched in the liver. This liver targeting can further be used for the targeted diagnosis, prevention and/or treatment of liver diseases or disorders, such as hepatitis, malaria, hepatocellular carcinoma (HCC), as well as for the prevention of HAV, HBV, HCV and/or HDV infection. The present invention relates to pharmaceutical compositions comprising said hydrophobic modified preS-derived peptide(s) and the compound(s) to be specifically delivered to the liver. The present invention furthermore relates to a method for the combined treatment of a liver disease and the prevention of HAV, HBV, HCV and/or HDV infection. The present invention relates also to the use of the preS-derived peptides in gene therapy and the delivery of immunogenic epitopes for hepatocyte-mediated antigen presentation to activate liver-directed immunological responses.

5. 发明申请

US20110027183A1 Hydrophobic Modified Pres-Derived Peptides of Hepatitis B Virus (HBV) and Their Use as Vehicles for the Specific Delivery of Compounds to the Liver 有权
标题翻译：乙型肝炎病毒（HBV）的疏水性修饰的预先衍生的肽及其作为将化合物特异性递送至肝脏的载体的用途
公开(公告)号：US20110027183A1
公开(公告)日：2011-02-03
申请号：US12864197
申请日：2009-01-26
申请人： Walter Mier , Uwe Haberkorn , Stephan Urban
发明人： Walter Mier , Uwe Haberkorn , Stephan Urban
IPC分类号： A61K49/00 , C07K7/06 , C07K7/08 , C07K14/00 , A61K39/395 , A61K38/44 , A61K35/76 , A61K38/21 , A61K31/7105 , A61K31/7052 , A61K39/00 , A61K38/16 , A61K38/10 , A61K38/08 , C12N15/63 , G01N33/53 , A61P1/16 , A61P37/04 , A61P31/12
CPC分类号： C07K14/005 , A61K38/162 , A61K2039/6075 , C07K2319/033 , C12N2730/10122 , C12N2810/6036 , Y02A50/41 , Y02A50/412 , Y02A50/423 , Y02A50/463
摘要： The present invention relates to hydrophobic modified preS-derived peptides of hepatitis B virus (HBV) which are versatile vehicles for the specific delivery of compounds to the liver, preferably to hepatocytes, in vitro as well as in vivo. Any kind of compound, but in particular drugs, such as interferons, viral reverse transcriptase inhibitors or core assembly inhibitors, and/or labels can be specifically targeted to the liver and so be enriched in the liver. This liver targeting can further be used for the targeted diagnosis, prevention and/or treatment of liver diseases or disorders, such as hepatitis, malaria, hepatocellular carcinoma (HCC), as well as for the prevention of HAV, HBV, HCV and/or HDV infection. The present invention relates to pharmaceutical compositions comprising said hydrophobic modified preS-derived peptide(s) and the compound(s) to be specifically delivered to the liver. The present invention furthermore relates to a method for the combined treatment of a liver disease and the prevention of HAV, HBV, HCV and/or HDV infection. The present invention relates also to the use of the preS-derived peptides in gene therapy and the delivery of immunogenic epitopes for hepatocyte-mediated antigen presentation to activate liver-directed immunological responses.
摘要翻译：本发明涉及乙型肝炎病毒（HBV）的疏水性修饰的preS-衍生肽，其是用于在体外和体内特异性递送化合物至肝脏，优选肝细胞的通用载体。任何种类的化合物，特别是药物，例如干扰素，病毒逆转录酶抑制剂或核心组装抑制剂和/或标记物可以特异性靶向肝脏，因此富含肝脏。该肝靶向可进一步用于肝病，疟疾，肝细胞癌（HCC）等肝病或疾病的靶向诊断，预防和/或治疗，以及预防HAV，HBV，HCV和/或 HDV感染。本发明涉及包含所述疏水性修饰的preS-衍生的肽和要特异性递送至肝脏的化合物的药物组合物。本发明还涉及一种联合治疗肝脏疾病和预防HAV，HBV，HCV和/或HDV感染的方法。本发明还涉及preS衍生的肽在基因治疗中的用途，以及用于肝细胞介导的抗原呈递的免疫原性表位的递送以激活肝脏免疫应答。

6. 发明申请

US20120122788A1 E-POLYLYSINE CONJUGATES AND THE USE THEREOF 有权
标题翻译： E-POLYLYSINE CONJUGATES及其用途
公开(公告)号：US20120122788A1
公开(公告)日：2012-05-17
申请号：US13384789
申请日：2010-07-09
申请人： Armin Kuebelbeck , Gregor Larbig , Walter Mier , Barbro Beijer , Uwe Haberkorn
发明人： Armin Kuebelbeck , Gregor Larbig , Walter Mier , Barbro Beijer , Uwe Haberkorn
IPC分类号： A61K47/48 , C07K14/00 , C07K7/08 , A61P13/12 , C07K7/06
CPC分类号： A61K47/48315 , A61K47/542 , A61K47/645 , A61K49/085 , A61K49/146 , A61K51/0497 , A61K51/088 , C07K7/00 , C07K7/06 , C07K7/08 , C07K14/00
摘要： The present invention relates to ε-polylysine conjugates, in particular conjugates of ε-polylysine with compounds carrying carboxyl groups, and to the preparation and use thereof for targeting of the kidney.
摘要翻译：本发明涉及多聚赖氨酸缀合物，特别是＆amp;聚赖氨酸与携带羧基的化合物的缀合物，以及其用于靶向靶的制备和用途。

7. 发明授权

US09078929B2 ε-Polylysine conjugates and the use thereof 有权
标题翻译：聚赖氨酸缀合物及其用途
公开(公告)号：US09078929B2
公开(公告)日：2015-07-14
申请号：US13384789
申请日：2010-07-09
申请人： Armin Kuebelbeck , Gregor Larbig , Walter Mier , Barbro Beijer , Uwe Haberkorn
发明人： Armin Kuebelbeck , Gregor Larbig , Walter Mier , Barbro Beijer , Uwe Haberkorn
IPC分类号： A61K38/00 , A61P13/12 , C07K5/00 , C07K7/00 , C07K16/00 , C07K17/00 , A61K38/04 , A61K47/48 , A61K49/08 , A61K51/04 , C07K7/06 , C07K14/00 , C07K7/08
CPC分类号： A61K47/48315 , A61K47/542 , A61K47/645 , A61K49/085 , A61K49/146 , A61K51/0497 , A61K51/088 , C07K7/00 , C07K7/06 , C07K7/08 , C07K14/00
摘要： The present invention relates to ε-polylysine conjugates, in particular conjugates of ε-polylysine with compounds carrying carboxyl groups, and to the preparation and use thereof for targeting of the kidney.
摘要翻译：本发明涉及多聚赖氨酸缀合物，特别是＆amp;聚赖氨酸与携带羧基的化合物的缀合物，以及其用于靶向靶的制备和用途。

8. 发明申请

US20070202047A1 Polyamine-substituted ligands for use as contrast agents 审中-公开
标题翻译：用作造影剂的多胺取代的配体
公开(公告)号：US20070202047A1
公开(公告)日：2007-08-30
申请号：US11649503
申请日：2007-01-04
申请人： Markus Wolf , Ulrike Bauder-Wust , Uwe Haberkorn , Michael Eisenhut , Walter Mier
发明人： Markus Wolf , Ulrike Bauder-Wust , Uwe Haberkorn , Michael Eisenhut , Walter Mier
IPC分类号： A61K49/10 , C07F5/00 , C07D257/02
CPC分类号： C07D257/02 , A61K49/103 , A61K49/106
摘要： The present invention relates to a polyamine-substituted ligand for the preparation of a contrast agent derived from a chelating molecule selected from the group consisting of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) and diethylentriamine-pentaacetic acid (DTPA), wherein at least one of the carboxylic groups of the chelating molecule is reacted with an amine of formula HNR1R2 to form an amide bond, wherein R1, R2 are independently selected from the group consisting of H; (CH2)n—NR3R4; and R5; R3, R4 are independently selected from the group consisting of H; (CH2)m—NR6R7; and (CH2)m-1—CH3; R6, R7 are independently selected from the group consisting of H; and (CH2)o-1—CH3; n, m, o are independently 2, 3, or 4; R5 is of formula and optionally at least one of the carboxylic groups of the chelating molecule is further reacted with a monoalkylamine having 1 to 18 carbon atoms to form an amide bond; provided that at least one of R1, R2 is other than H. Furthermore, the invention relates to contrast agents for magnetic resonance imaging (MRI) comprising said ligands and in-vivo diagnostic methods based on MRI using said contrast agents.
摘要翻译：本发明涉及用于制备衍生自螯合分子的造影剂的多胺取代配体，所述螯合分子选自1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸（DOTA ）和二乙基三胺五乙酸（DTPA），其中螯合分子的至少一个羧基与式HNR 1 R 2的胺反应形成酰胺键，其中R 1，R 2，R 2独立地选自H; （CH 2）n - NR 3 - 3 - - - - - - - 和R 5; R 3，R 4，R 4独立地选自H; （CH 2 CH 2）m -NR 6 R 6 R 7 R 7，和（CH 2 CH 2）m-1 -CH 3 3; R 6，R 7，R 7独立地选自H; 和（CH 2）2 -O-1 -CH 3; n，m，o分别为2,3或4; R 5是下式，并且任选地，螯合分子的至少一个羧酸基团与具有1至18个碳原子的单烷基胺进一步反应以形成酰胺键; 条件是R 1，R 2和R 2中的至少一个不是H.此外，本发明涉及用于包含所述配体的磁共振成像（MRI）的造影剂，并且在 - 使用所述造影剂的基于MRI的体内诊断方法。

9. 发明授权

US09562076B2 Hydrophobic modified pres-derived peptides of hepatitis B virus (HBV) and their use as HBV and HDV entry inhibitors 有权
标题翻译：乙型肝炎病毒（HBV）的疏水性修饰的前衍生肽及其作为HBV和HDV进入抑制剂的用途
公开(公告)号：US09562076B2
公开(公告)日：2017-02-07
申请号：US12863663
申请日：2009-01-26
申请人： Walter Mier , Stephan Urban
发明人： Walter Mier , Stephan Urban
IPC分类号： A61K39/29 , C07K7/08 , C07K14/02 , A61P31/20 , C07K14/005 , A61K47/48 , A61K39/12 , A61K38/00
CPC分类号： C07K14/005 , A61K38/00 , A61K39/12 , A61K39/292 , A61K47/54 , A61K47/542 , A61K47/544 , A61K47/554 , C12N2730/10122 , C12N2730/10134
摘要： The present invention relates to hydrophobic modified preS-derived peptides of hepatitis B virus (HBV) which are derived from a HBV preS consensus sequence and are N-terminal preferably acylated and optional C-terminal modified. These hydrophobic modified preS-derived peptides of HBV are very effective HBV entry inhibitors as well as HDV entry inhibitors and are, thus, suitable for the inhibition of HBV and/or HDV infection, prevention of primary HBV and/or HDV infection as well as treatment of (chronic) hepatitis B and/or D. The present invention further relates to pharmaceutical and vaccine compositions comprising these hydrophobic modified preS-derived peptides of HBV.
摘要翻译：本发明涉及衍生自HBV preS共有序列并且N末端优选酰化并任选C末端修饰的乙型肝炎病毒（HBV）的疏水性修饰的preS-衍生肽。 HBV的这些疏水性修饰的preS-衍生肽是非常有效的HBV进入抑制剂以及HDV进入抑制剂，因此适合于抑制HBV和/或HDV感染，预防原发性HBV和/或HDV感染以及治疗（慢性）乙型肝炎和/或D.本发明还涉及含有这些疏水性修饰的preS-衍生肽的HBV的药物和疫苗组合物。

10. 发明申请

US20110020397A1 HYDROPHOBIC MODIFIED PRES-DERIVED PEPTIDES OF HEPATITIS B VIRUS (HBV) AND THEIR USE AS HBV AND HDV ENTRY INHIBITORS 有权
标题翻译：乙型肝炎病毒（HBV）及其用作乙型肝炎病毒和高密度脂蛋白入侵抑制剂的疏水性改性预先导入的肽
公开(公告)号：US20110020397A1
公开(公告)日：2011-01-27
申请号：US12863663
申请日：2009-01-26
申请人： Walter Mier , Stephan Urban
发明人： Walter Mier , Stephan Urban
IPC分类号： A61K39/29 , C07K7/08 , C07K14/02 , A61P31/20
CPC分类号： C07K14/005 , A61K38/00 , A61K39/12 , A61K39/292 , A61K47/54 , A61K47/542 , A61K47/544 , A61K47/554 , C12N2730/10122 , C12N2730/10134
摘要： The present invention relates to hydrophobic modified preS-derived peptides of hepatitis B virus (HBV) which are derived from a HBV preS consensus sequence and are N-terminal preferably acylated and optional C-terminal modified. These hydrophobic modified preS-derived peptides of HBV are very effective HBV entry inhibitors as well as HDV entry inhibitors and are, thus, suitable for the inhibition of HBV and/or HDV infection, prevention of primary HBV and/or HDV infection as well as treatment of (chronic) hepatitis B and/or D. The present invention further relates to pharmaceutical and vaccine compositions comprising these hydrophobic modified preS-derived peptides of HBV.
摘要翻译：本发明涉及衍生自HBV preS共有序列并且N末端优选酰化并任选C末端修饰的乙型肝炎病毒（HBV）的疏水性修饰的preS-衍生肽。 HBV的这些疏水性修饰的preS-衍生肽是非常有效的HBV进入抑制剂以及HDV进入抑制剂，因此适合于抑制HBV和/或HDV感染，预防原发性HBV和/或HDV感染以及治疗（慢性）乙型肝炎和/或D.本发明还涉及含有这些疏水性修饰的preS-衍生肽的HBV的药物和疫苗组合物。

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