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21. 发明申请

WO0220769A9 HUMAN AND MOUSE TARGETING PEPTIDES IDENTIFIED BY PHAGE DISPLAY 审中-公开
标题翻译：由PHAGE显示识别的人和小鼠靶向肽
公开(公告)号：WO0220769A9
公开(公告)日：2003-09-04
申请号：PCT/US0127692
申请日：2001-09-07
申请人： UNIV TEXAS , ARAP WADIH , PASQUALINI RENATA
发明人： ARAP WADIH , PASQUALINI RENATA
IPC分类号： C12N15/09 , A61K35/14 , A61K38/00 , A61K39/00 , A61K45/00 , A61K47/42 , A61K47/48 , A61K48/00 , A61K49/00 , A61P3/10 , A61P9/00 , A61P9/10 , A61P13/08 , A61P15/18 , A61P19/02 , A61P27/02 , A61P29/00 , A61P31/04 , A61P31/12 , A61P35/00 , A61P37/06 , A61P43/00 , C07K1/04 , C07K5/08 , C07K5/10 , C07K7/06 , C07K7/08 , C07K14/00 , C07K14/005 , C07K16/08 , C07K17/00 , C12N7/00 , C12N15/07 , C12N15/10 , C12N15/861 , C12N15/864 , C12Q1/02 , C12Q1/70 , C40B40/02 , C12N15/03 , A61K38/03 , A61K38/04 , A61K38/08 , A61K38/17 , C07K7/00 , C07K7/04 , C07K17/02 , C12N15/73 , C12N15/74 , C12N15/75
CPC分类号： C40B40/02 , A61K38/00 , A61K39/00 , A61K48/00 , A61K2039/5256 , C07K1/047 , C07K7/06 , C07K7/08 , C07K14/001 , C12N15/1037 , C12N15/86 , C12N2710/10345 , C12N2750/14143 , C12N2810/40
摘要： The present invention concerns methods and compositions for in vivo and in vitro targeting. A large number of targeting peptides directed towards human organs, tissues or cell types are disclosed. The peptides are of use for targeted delivery of therapeutic agents, including but not limited to gene therapy vectors. A novel class of gene therapy vectors is disclosed. Certain of the disclosed peptides have therapeutic use for inhibiting angiogenesis, inhibiting tumor growth, inducing apoptosis, inhibiting pregnancy or inducing weight loss. Methods of identifying novel targeting peptides in humans, as well as identifying endogenous receptor-ligand pairs are disclosed. Methods of identifying novel infectious agents that are causal for human disease states are also disclosed. A novel mechanism for inducing apoptosis is further disclosed.
摘要翻译：本发明涉及用于体内和体外靶向的方法和组合物。公开了大量针对人器官，组织或细胞类型的靶向肽。肽可用于靶向递送治疗剂，包括但不限于基因治疗载体。公开了一类新型的基因治疗载体。某些所公开的肽具有抑制血管发生，抑制肿瘤生长，诱导凋亡，抑制妊娠或引起体重减轻的治疗用途。公开了鉴定人中新靶向肽的方法，以及鉴定内源性受体 - 配体对。还公开了鉴定对人类疾病状态有影响的新型感染因子的方法。进一步公开了诱导细胞凋亡的新机制。

22. 发明申请

WO0220822A2 BIOPANNING AND RAPID ANALYSIS OF SELECTIVE INTERACTIVE LIGANDS (BRASIL) 审中-公开
标题翻译：选择性交互式配置（BRASIL）的生成和快速分析
公开(公告)号：WO0220822A2
公开(公告)日：2002-03-14
申请号：PCT/US0128124
申请日：2001-09-07
申请人： UNIV TEXAS , ARAP WADIH , PASQUALINI RENATA
发明人： ARAP WADIH , PASQUALINI RENATA
IPC分类号： C12N15/09 , A61K31/225 , A61K31/23 , A61K31/56 , A61K31/683 , A61K31/685 , A61K31/688 , A61K31/713 , A61K35/12 , A61K35/76 , A61K38/00 , A61K39/00 , A61K39/02 , A61K39/12 , A61K39/395 , A61K45/00 , A61K47/42 , A61K47/48 , A61K48/00 , A61K49/00 , A61P3/10 , A61P7/00 , A61P9/00 , A61P9/10 , A61P13/02 , A61P19/02 , A61P25/28 , A61P29/00 , A61P31/04 , A61P31/10 , A61P31/12 , A61P31/18 , A61P35/00 , A61P35/02 , A61P37/02 , A61P37/04 , A61P43/00 , C07K1/04 , C07K5/08 , C07K5/10 , C07K7/04 , C07K7/06 , C07K7/08 , C07K14/00 , C07K14/005 , C07K14/47 , C07K14/52 , C07K16/08 , C07K16/18 , C07K19/00 , C12N7/02 , C12N15/10 , C12N15/861 , C12N15/864 , C12Q1/02 , C12Q1/70 , G01N33/50 , G01N33/53 , G01N33/566 , C12Q
CPC分类号： C07K14/52 , A61K38/00 , A61K48/00 , A61K2039/5256 , C07K1/047 , C07K7/06 , C12N15/1037 , C12N2810/40
摘要： The present invention concerns novel methods of identifying peptide sequences that selectively bind to targets. In alternative embodiments, targets may comprise cells or clumps of cells, particles attached to chemicals compounds, molecules or aggregates, or parasites. In preferred embodiments, target cells are sorted before exposure to the phage library. The general method, Biopanning and Rapid Analysis of Selective Interactive Ligands (BRASIL) provides for rapid and efficient separation of phage that bind to targets, while preserving unbound phage. BRASIL may be used in preselection procedure to subract phage that bind non-specifically to a first target before exposing the subtracted library to a second target. Certain embodiments concern targeting peptides identified by BRASIL and methods of use of such peptides for targeted delivera of therapeutic agents or imaging agents or diagnosis or treatment of diseases. Novel compositions comprising a first phase, second phase, target and a phage library are also disclosed.
摘要翻译：本发明涉及鉴定选择性结合靶标的肽序列的新方法。在替代实施方案中，靶可以包含细胞或细胞团，附着于化学物质的化合物，分子或聚集体或寄生虫的颗粒。在优选实施方案中，靶细胞在暴露于噬菌体文库之前进行分选。选择性交互式配体（BRASIL）的生物平衡和快速分析的一般方法提供了快速有效的分离与靶标结合的噬菌体，同时保留未结合的噬菌体。 BRASIL可以用于预选过程，以将噬菌体非特异性结合到第一靶标，然后将减去的文库暴露于第二靶标。某些实施方案涉及由BRASIL鉴定的靶向肽以及使用这些肽用于治疗剂或成像剂的靶向递送或诊断或治疗疾病的方法。还公开了包含第一相，第二相，靶和噬菌体文库的新型组合物。

23. 发明专利

JP2010031038A Molecule homing to various selected organ or tissue 审中-公开
标题翻译：分子喜欢各种精选的组织或组织
公开(公告)号：JP2010031038A
公开(公告)日：2010-02-12
申请号：JP2009254478
申请日：2009-11-05
申请人： Burnham Inst , ザバーナムインスティチュート
发明人： RAJOTTE DANIEL , PASQUALINI RENATA , RUOSLAHTI ERKKI I
IPC分类号： C07K7/06 , C12N15/09 , A61K31/195 , A61K35/76 , A61K38/00 , A61K45/00 , A61K47/16 , A61K47/20 , A61K47/42 , A61K47/48 , A61K48/00 , A61P1/04 , A61P1/16 , A61P1/18 , A61P5/38 , A61P11/00 , A61P15/00 , A61P17/00 , A61P27/02 , A61P35/00 , A61P35/04 , A61P43/00 , C07C233/46 , C07K7/08 , C07K14/005 , C07K14/705 , G01N33/68
CPC分类号： C07K7/06 , A61K31/195 , A61K38/00 , A61K47/6425 , C07K7/08 , Y10S977/808 , Y10S977/911 , Y10S977/912
摘要： PROBLEM TO BE SOLVED: To identify a molecule homable to a specific organ or tissue. SOLUTION: There are provided a molecule selectively homing to various normal organs or tissues (including lung, pancreas, skin, retina, prostate, ovary, lymph node, adrenal gland, liver or gut) and a molecule selectively homing to tumor-bearing organs or tissues (including pancreas bearing pancreatic tumor or lung bearing lung tumor). Also, there are provided conjugates comprising an organ or tissue homing molecule linked to a moiety. Such functional group can be, for example, a therapeutic agent or a detectable agent. Further, there are provided a method of identifying a membrane dipeptidase (MDP)-binding homing molecule that selectively homes to lung endothelium. COPYRIGHT: (C)2010,JPO&INPIT
摘要翻译：要解决的问题：鉴定可与特定器官或组织相容的分子。解决方案：提供选择性归巢到各种正常器官或组织（包括肺，胰腺，皮肤，视网膜，前列腺，卵巢，淋巴结，肾上腺，肝脏或肠）的分子和选择性归巢到肿瘤 - 携带器官或组织（包括携带胰腺肿瘤或携带肺肿瘤的肺）。而且，提供了包含与部分连接的器官或组织归巢分子的缀合物。这样的官能团可以是例如治疗剂或可检测剂。此外，提供了一种鉴定选择性地适应于肺内皮的膜二肽酶（MDP）结合归巢分子的方法。版权所有（C）2010，JPO＆INPIT

24. 发明专利

JP2007204483A Molecules that home to organ or tissue selected in vivo and methods of identifying same 审中-公开
标题翻译：分析家庭中选择的组织或组织和体检方法
公开(公告)号：JP2007204483A
公开(公告)日：2007-08-16
申请号：JP2007056453
申请日：2007-03-06
申请人： Burnham Inst , ザバーナムインスティテュート
发明人： RUOSLAHTI ERKKI , PASQUALINI RENATA
IPC分类号： A61K9/127 , C40B40/10 , A61K45/00 , A61K47/42 , A61K47/48 , A61K49/00 , A61P35/00 , C07K1/04 , C07K1/13 , C07K1/14 , C07K5/10 , C07K7/06 , C07K7/08 , C07K14/47 , C12N15/09 , G01N33/15 , G01N33/50 , G01N33/53 , G01N33/566 , G01N33/567
CPC分类号： G01N33/5008 , A61K47/6425 , C07K1/047 , G01N33/5011 , G01N33/5044 , G01N33/5058 , G01N33/5067 , G01N33/5088 , G01N33/567
摘要： PROBLEM TO BE SOLVED: To provide molecules that home to one or more of selected organs or tissues. SOLUTION: An enriched library fraction includes a plurality of peptides or peptide imitations that selectively home to a selected organ or tissue. The enriched library fraction is recovered by in vivo panning including the following steps. The enriched library fraction : (a) a step of prescribing a library of the peptides or the peptide imitations to a nonhuman subject, and here, a step of joining the respective peptides or peptide imitations to a tag for facilitating recovery of the peptides or peptide imitations, (b) a step of gathering samples of the selected organ or tissue, and (c) a step of recovering the enriched library fractions that home to the selected organ or tissue. COPYRIGHT: (C)2007,JPO&INPIT
摘要翻译：要解决的问题：提供一个或多个所选择的器官或组织的分子。解决方案：富集的文库级分包括选择性地置于所选器官或组织的多个肽或肽模拟物。通过体内淘选回收富集的文库级分，包括以下步骤。富集的文库部分：（a）向非人类受试者处方肽或肽模拟文库的步骤，这里，将各肽或肽模仿连接到标签以促进肽或肽的回收的步骤模仿，（b）收集所选择的器官或组织的样品的步骤，和（c）回收所选器官或组织所在的富集的文库级分的步骤。版权所有（C）2007，JPO＆INPIT

25. 发明公开

EP1150701A4 HOMING PRO-APOPTOTIC CONJUGATES AND METHODS OF USING SAME 审中-公开
标题翻译： ZIELANSTEUERNDE凋亡偶联物及其它们的使用方法
公开(公告)号：EP1150701A4
公开(公告)日：2003-03-26
申请号：EP00911617
申请日：2000-01-21
申请人： BURNHAM INST
发明人： ELLERBY H MICHAEL , BREDESEN DALE E , PASQUALINI RENATA , RUOSLAHTI ERKKI I
IPC分类号： A61K38/00 , A61K47/48 , A61P13/08 , A61P35/00 , C07K7/00 , C07K14/00 , A61K38/04 , A61K39/00 , A61K39/02 , C07K2/00 , C07K4/00 , C07K5/00 , C07K16/00 , C07K17/00
CPC分类号： A61K47/62
摘要： The present invention provides a homing pro-apoptotic conjugate, which includes a tumor homing molecule that selectively homes to a selected mammalian cell type or tissue linked to an antimicrobial peptide, where the conjugate is selectively internalized by the mammalian cell type or tissue and exhibits high toxicity thereto, and where the antimicrobial peptide has low mammalian cell toxicity when not linked to the tumor homing molecule. A homing pro-apoptotic conjugate of the invention can be, for example, CNGRC-GG-D(KLAKLAK)2 or ACDCRGDCFC-GG-D(KLAKLAK)2. The conjugates of the invention are useful, for example, for treating a patient with a tumor having angiogenic vasculature.

26. 发明公开

EP1161149A4 NG2/HM PROTEOGLYCAN-BINDING PEPTIDES THAT HOME TO ANGIOGENIC VASCULATURE AND RELATED METHODS 审中-公开
标题翻译：船舶血管新生具体NG2 / HM蛋白多糖结合肽及相关方法
公开(公告)号：EP1161149A4
公开(公告)日：2002-04-10
申请号：EP00908659
申请日：2000-02-16
申请人： BURNHAM INST
发明人： BURG MICHAEL A , PASQUALINI RENATA , ARAP WADIH , RUOSLAHTI ERKKI I , STALLCUP WILLIAM B
IPC分类号： A61K38/00 , C07K7/06 , A61K47/48 , A61P35/00 , C07K7/08
CPC分类号： C07K7/06 , A61K38/00
摘要： The present invention provides angiogenic vasculature homing molecules that bind to NG2/HM proteoglycan, including, for example, a peptide comprising the amino acid sequence TAASGVRSMH (SEQ ID NO:1) or LTLRWVGLMS (SEQ ID NO:2). The invention also provides conjugates comprising an angiogenic vasculature homing molecule linked to a moiety such as a drug, a cytotoxic agent, a chemotherapeutic agent, or a detectable agent. The invention additionally provides a method of targeting angiogenic vasculature in a tumor in vivo by contacting the angiogenic vasculature with an angiogenic vasculature homing molecule that selectively homes to a NG2/HM proteoglycan, wherein the angiogenic vasculature homing molecule is not an antibody. The invention additionally provides a method of inhibiting angiogenesis in a tumor of a subject by administering to the subject a conjugate comprising a moiety linked to an angiogenic vasculature homing molecule that selectively binds a NG2/HM proteoglycan, wherein the angiogenic vasculature homing molecule is not an antibody.

27. 发明申请

WO9810795A9 TUMOR HOMING MOLECULES, CONJUGATES DERIVED THEREFROM, AND METHODS OF USING SAME 审中-公开
标题翻译：肿瘤分泌物，其衍生物及其使用方法
公开(公告)号：WO9810795A9
公开(公告)日：2001-06-21
申请号：PCT/US9716086
申请日：1997-09-10
申请人： BURNHAM INST
发明人： RUOSLAHTI ERKKI , PASQUALINI RENATA
IPC分类号： C12N15/09 , A61K31/704 , A61K38/00 , A61K39/395 , A61K47/48 , A61K48/00 , A61K51/08 , A61P35/00 , C07K14/78 , C07K16/18 , C12N15/10 , C40B40/02 , A61K31/70 , C07K1/04 , C07K7/06 , C07K14/00
CPC分类号： C40B40/02 , A61K47/62 , A61K51/082 , A61K51/088 , C12N15/1037
摘要： The present invention provides tumor homing molecules, which selectively home to a tumor. The invention also provides methods of using a tumor homing molecule to target an agent such as a drug to a selected tumor or to identify the target molecule expressed by the tumor. The invention also provides methods of targeting a tumor containing angiogenic vasculature by contacting the tumor with a molecule that specifically binds an alpha v-containing integrin. The invention further provides molecules that can selectively home to angiogenic vasculature. In addition, the invention provides a target molecule, which is specifically bound by a tumor homing molecule and is expressed by angiogenic vasculature. The invention also provides antibodies that bind to the target molecule and peptidomimetics that competitively inhibit binding of a ligand to the target molecule.
摘要翻译：本发明提供了肿瘤归巢分子，其选择性地归巢于肿瘤。本发明还提供使用肿瘤归巢分子将药物如药物靶向所选择的肿瘤或鉴定由肿瘤表达的靶分子的方法。本发明还提供了通过使肿瘤与特异性结合含αV的整联蛋白的分子接触来靶向含有血管生成脉管系统的肿瘤的方法。本发明进一步提供可以选择性地归属于血管生成脉管系统的分子。此外，本发明提供了靶分子，其特异性地被肿瘤归巢分子结合并且由血管生成脉管系统表达。本发明还提供了结合靶分子的抗体和竞争性抑制配体与靶分子结合的肽模拟物。

28. 发明申请

WO0042973A2 HOMING PRO-APOPTOTIC CONJUGATES AND METHODS OF USING SAME 审中-公开
标题翻译： HOMING PRO-APOPTOTIC CONJUGATES及其使用方法
公开(公告)号：WO0042973A2
公开(公告)日：2000-07-27
申请号：PCT/US0001602
申请日：2000-01-21
申请人： BURNHAM INST
发明人： ELLERBY H MICHAEL , BREDESEN DALE E , PASQUALINI RENATA , RUOSLAHTI ERKKI I
IPC分类号： A61K38/00 , A61K47/48 , A61P13/08 , A61P35/00 , C07K7/00 , C07K14/00 , A61K
CPC分类号： A61K47/62
摘要： The present invention provides a homing pro-apoptotic conjugate, which includes a tumor homing molecule that selectively homes to a selected mammalian cell type or tissue linked to an antimicrobial peptide, where the conjugate is selectively internalized by the mammalian cell type or tissue and exhibits high toxicity thereto, and where the antimicrobial peptide has low mammalian cell toxicity when not linked to the tumor homing molecule. A homing pro-apoptotic conjugate of the invention can be, for example, CNGRC-GG-D(KLAKLAK)2 or ACDCRGDCFC-GG-D(KLAKLAK)2. The conjugates of the invention are useful, for example, for treating a patient with a tumor having angiogenic vasculature.
摘要翻译：本发明提供归巢促细胞程序死亡缀合物，其包括选择性地归巢至选择的哺乳动物细胞类型或与抗微生物肽连接的组织的肿瘤归巢分子，其中所述缀合物被哺乳动物细胞类型或组织选择性内化并表现出高毒性，并且当抗微生物肽在不与肿瘤归巢分子连接时具有低哺乳动物细胞毒性。本发明的归巢促细胞程序死亡缀合物可以是例如CNGRC-GG-D（KLAKLAK）2或ACDCRGDCFC-GG-D（KLAKLAK）2。例如，本发明的缀合物可用于治疗具有血管生成脉管系统的肿瘤的患者。

29. 发明申请

WO9810795A2 TUMOR HOMING MOLECULES, CONJUGATES DERIVED THEREFROM, AND METHODS OF USING SAME 审中-公开
标题翻译：肿瘤分泌物，其衍生物及其使用方法
公开(公告)号：WO9810795A2
公开(公告)日：1998-03-19
申请号：PCT/US9716086
申请日：1997-09-10
申请人： BURNHAM INST
发明人： RUOSLAHTI ERKKI , PASQUALINI RENATA
IPC分类号： C12N15/09 , A61K31/704 , A61K38/00 , A61K39/395 , A61K47/48 , A61K48/00 , A61K51/08 , A61P35/00 , C07K14/78 , C07K16/18 , C12N15/10 , C40B40/02 , C07K14/00 , G01N33/53
CPC分类号： C40B40/02 , A61K47/62 , A61K51/082 , A61K51/088 , C12N15/1037
摘要： The present invention provides tumor homing molecules, which selectively home to a tumor. The invention also provides methods of using a tumor homing molecule to target an agent such as a drug to a selected tumor or to identify the target molecule expressed by the tumor. The invention also provides methods of targeting a tumor containing angiogenic vasculature by contacting the tumor with a molecule that specifically binds an alpha v-containing integrin. The invention further provides molecules that can selectively home to angiogenic vasculature. In addition, the invention provides a target molecule, which is specifically bound by a tumor homing molecule and is expressed by angiogenic vasculature. The invention also provides antibodies that bind to the target molecule and peptidomimetics that competitively inhibit binding of a ligand to the target molecule.
摘要翻译：本发明提供了肿瘤归巢分子，其选择性地归巢于肿瘤。本发明还提供使用肿瘤归巢分子将药物如药物靶向所选择的肿瘤或鉴定由肿瘤表达的靶分子的方法。本发明还提供了通过使肿瘤与特异性结合含αV的整联蛋白的分子接触来靶向含有血管生成脉管系统的肿瘤的方法。本发明进一步提供可以选择性地归属于血管生成脉管系统的分子。此外，本发明提供了靶分子，其特异性地被肿瘤归巢分子结合并且由血管生成脉管系统表达。本发明还提供了结合靶分子的抗体和竞争性抑制配体与靶分子结合的肽模拟物。

30. 发明申请

WO9946284A9 MOLECULES THAT HOME TO VARIOUS SELECTED ORGANS OR TISSUES 审中-公开
标题翻译：分类为各种各样的选择的器官或组织
公开(公告)号：WO9946284A9
公开(公告)日：1999-11-18
申请号：PCT/US9905284
申请日：1999-03-10
申请人： BURNHAM INST
发明人： RAJOTTE DANIEL , PASQUALINI RENATA , RUOSLAHTI ERKKI I
IPC分类号： C12N15/09 , A61K31/195 , A61K38/00 , A61K45/00 , A61K47/48 , A61K48/00 , A61P35/00 , A61P35/04 , A61P43/00 , C07C233/46 , C07K7/06 , C07K7/08 , C07K14/705 , A61K38/08 , A61K38/10
CPC分类号： C07K7/06 , A61K31/195 , A61K38/00 , A61K47/6425 , C07K7/08 , Y10S977/808 , Y10S977/911 , Y10S977/912
摘要： The present invention provides molecules that selectively home to various normal organs or tissues, including to lung, pancreas, skin, retina, prostate, ovary, lymph node, adrenal gland, liver or gut; and provides molecules that selectively home to tumor bearing organs or tissues, including to pancreas bearing a pancreatic tumor or to lung bearing a lung tumor. The invention also provides conjugates, comprising an organ or tissue homing molecule linked to a moiety. Such a moiety can be, for example, a therapeutic agent or a detectable agent. The invention also provides a method of identifying a membrane dipeptidase (MDP)-binding homing molecule that selectively homes to lung endothelium. The method includes the steps of contacting MDP with one or more molecules; and determining specific binding of a molecule to the MDP, where the presence of specific binding identifies the molecule as a MDP-binding homing molecule that selectively homes to lung endothelium. Such MDP-binding homing molecules can be linked to a moiety and, when administered to a subject as a conjugate, can selectively direct the moiety to lung endothelium in the subject.
摘要翻译：本发明提供了选择性地归属于各种正常器官或组织，包括肺，胰腺，皮肤，视网膜，前列腺，卵巢，淋巴结，肾上腺，肝脏或肠道的分子; 并提供选择性地置于携带肿瘤的器官或组织，包括携带胰腺肿瘤的胰腺或携带肺肿瘤的肺的分子。本发明还提供缀合物，其包含与部分连接的器官或组织归巢分子。这样的部分可以是例如治疗剂或可检测剂。本发明还提供了鉴定选择性地适应于肺内皮的膜二肽酶（MDP）结合归巢分子的方法。该方法包括使MDP与一种或多种分子接触的步骤; 并确定分子与MDP的特异性结合，其中特异性结合物的存在将该分子鉴定为选择性地置于肺内皮的MDP结合归巢分子。这种MDP结合的归巢分子可以连接到部分上，并且当作为结合物施用于受试者时，可以选择性地将该部分导向受试者的肺内皮。

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