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1.发明申请Polymeric Carriers of Therapeutic Agents and Recognition Moieties for Antibody-Based Targeting of Disease Sites 有权治疗剂的聚合载体和用于基于抗体靶向疾病部位的识别部分公开(公告)号：US20120040431A1
公开(公告)日：2012-02-16
申请号：US13246389
申请日：2011-09-27
CPC分类号： A61K47/48315 , A61K31/4745 , A61K31/704 , A61K38/05 , A61K47/556 , A61K47/61 , A61K47/62 , A61K47/645 , A61K47/646 , A61K47/65 , A61K47/665 , A61K47/6951 , B82Y5/00 , C07K14/001 , C08B37/0021 , C08G83/003 , C08G83/004 , Y02A50/403
摘要： The present invention concerns methods and compositions for delivery of therapeutic agents to target cells, tissues or organisms. In preferred embodiments, the therapeutic agents are delivered in the form of therapeutic-loaded polymers that may comprise many copies of one or more therapeutic agents. In more preferred embodiments, the polymer may be conjugated to a peptide moiety that contains one or more haptens, such as HSG. The agent-polymer-peptide complex may be delivered to target cells by, for example, a pre-targeting technique utilizing bispecific or multispecific antibodies or fragments, having at least one binding arm that recognizes the hapten and at least a second binding arm that binds specifically to a disease or pathogen associated antigen, such as a tumor associated antigen. Methods for synthesizing and using such therapeutic-loaded polymers and their conjugates are provided.
摘要翻译： 本发明涉及用于将治疗剂递送至靶细胞，组织或生物体的方法和组合物。 在优选的实施方案中，治疗剂以治疗负荷聚合物的形式递送，其可以包含许多拷贝的一种或多种治疗剂。 在更优选的实施方案中，聚合物可以与含有一种或多种半抗原如HSG的肽部分缀合。 药剂 - 聚合物 - 肽复合物可以通过例如利用双特异性或多特异性抗体或片段的预靶向技术递送至靶细胞，所述双特异性或多特异性抗体或片段具有识别半抗原的至少一个结合臂和至少一个结合的结合臂 具体涉及疾病或病原体相关抗原，例如肿瘤相关抗原。 提供了合成和使用这种治疗负载型聚合物及其共轭物的方法。
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2.发明授权Polymeric carriers of therapeutic agents and recognition moieties for antibody-based targeting of disease sites 有权用于疾病部位的基于抗体的靶向治疗剂和识别部分的聚合物载体公开(公告)号：US08067006B2
公开(公告)日：2011-11-29
申请号：US12766092
申请日：2010-04-23
IPC分类号： G01N33/544 , G01N33/548 , G01N33/547 , A61K39/395 , A61K38/16 , A61K39/44 , C07K17/06 , C07K16/22
CPC分类号： A61K47/48315 , A61K31/4745 , A61K31/704 , A61K38/05 , A61K47/556 , A61K47/61 , A61K47/62 , A61K47/645 , A61K47/646 , A61K47/65 , A61K47/665 , A61K47/6951 , B82Y5/00 , C07K14/001 , C08B37/0021 , C08G83/003 , C08G83/004 , Y02A50/403
摘要： The present invention concerns methods and compositions for delivery of therapeutic agents to target cells, tissues or organisms. In preferred embodiments, the therapeutic agents are delivered in the form of therapeutic-loaded polymers that may comprise many copies of one or more therapeutic agents. In more preferred embodiments, the polymer may be conjugated to a peptide moiety that contains one or more haptens, such as HSG. The agent-polymer-peptide complex may be delivered to target cells by, for example, a pre-targeting technique utilizing bispecific or multispecific antibodies or fragments, having at least one binding arm that recognizes the hapten and at least a second binding arm that binds specifically to a disease or pathogen associated antigen, such as a tumor associated antigen. Methods for synthesizing and using such therapeutic-loaded polymers and their conjugates are provided.
摘要翻译： 本发明涉及用于将治疗剂递送至靶细胞，组织或生物体的方法和组合物。 在优选的实施方案中，治疗剂以治疗负荷聚合物的形式递送，其可以包含许多拷贝的一种或多种治疗剂。 在更优选的实施方案中，聚合物可以与含有一种或多种半抗原如HSG的肽部分缀合。 药剂 - 聚合物 - 肽复合物可以通过例如利用双特异性或多特异性抗体或片段的预靶向技术递送至靶细胞，所述双特异性或多特异性抗体或片段具有识别半抗原的至少一个结合臂和至少一个结合的结合臂 具体涉及疾病或病原体相关抗原，例如肿瘤相关抗原。 提供了合成和使用这种治疗负载型聚合物及其共轭物的方法。
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3.发明授权Polymeric carriers of therapeutic agents and recognition moieties for antibody-based targeting of disease sites 有权用于疾病部位的基于抗体的靶向治疗剂和识别部分的聚合物载体公开(公告)号：US08338140B2
公开(公告)日：2012-12-25
申请号：US13246389
申请日：2011-09-27
CPC分类号： A61K47/48315 , A61K31/4745 , A61K31/704 , A61K38/05 , A61K47/556 , A61K47/61 , A61K47/62 , A61K47/645 , A61K47/646 , A61K47/65 , A61K47/665 , A61K47/6951 , B82Y5/00 , C07K14/001 , C08B37/0021 , C08G83/003 , C08G83/004 , Y02A50/403
摘要： The present invention concerns methods and compositions for delivery of therapeutic agents to target cells, tissues or organisms. In preferred embodiments, the therapeutic agents are delivered in the form of therapeutic-loaded polymers that may comprise many copies of one or more therapeutic agents. In more preferred embodiments, the polymer may be conjugated to a peptide moiety that contains one or more haptens, such as HSG. The agent-polymer-peptide complex may be delivered to target cells by, for example, a pre-targeting technique utilizing bispecific or multispecific antibodies or fragments, having at least one binding arm that recognizes the hapten and at least a second binding arm that binds specifically to a disease or pathogen associated antigen, such as a tumor associated antigen. Methods for synthesizing and using such therapeutic-loaded polymers and their conjugates are provided.
摘要翻译： 本发明涉及用于将治疗剂递送至靶细胞，组织或生物体的方法和组合物。 在优选的实施方案中，治疗剂以治疗负荷聚合物的形式递送，其可以包含许多拷贝的一种或多种治疗剂。 在更优选的实施方案中，聚合物可以与含有一种或多种半抗原如HSG的肽部分缀合。 药剂 - 聚合物 - 肽复合物可以通过例如利用双特异性或多特异性抗体或片段的预靶向技术递送至靶细胞，所述双特异性或多特异性抗体或片段具有识别半抗原的至少一个结合臂和至少一个结合的结合臂 具体涉及疾病或病原体相关抗原，例如肿瘤相关抗原。 提供了合成和使用这种治疗负载型聚合物及其共轭物的方法。
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4.发明申请Polymeric Carriers of Therapeutic Agents and Recognition Moieties for Antibody-Based Targeting of Disease Sites 审中-公开治疗剂的聚合载体和用于基于抗体靶向疾病部位的识别部分公开(公告)号：US20080171067A1
公开(公告)日：2008-07-17
申请号：US11961436
申请日：2007-12-20
IPC分类号： A61K47/48
CPC分类号： B82Y5/00 , A61K47/556 , A61K47/61 , A61K47/6425 , A61K47/645 , A61K47/65 , A61K47/665 , A61K47/6835 , A61K47/6897 , A61K47/6951
摘要： The present invention concerns methods and compositions for delivery of therapeutic agents to target cells, tissues or organisms. In preferred embodiments, the therapeutic agents are delivered in the form of therapeutic-loaded polymers that may comprise many copies of one or more therapeutic agents. In more preferred embodiments, the polymer may be conjugated to a peptide moiety that contains one or more haptens, such as HSG. The agent-polymer-peptide complex may be delivered to target cells by, for example, a pre-targeting technique utilizing bispecific or multispecific antibodies or fragments, having at least one binding arm that recognizes the hapten and at least a second binding arm that binds specifically to a disease or pathogen associated antigen, such as a tumor associated antigen. Methods for synthesizing and using such therapeutic-loaded polymers and their conjugates are provided.
摘要翻译： 本发明涉及用于将治疗剂递送至靶细胞，组织或生物体的方法和组合物。 在优选的实施方案中，治疗剂以治疗负荷聚合物的形式递送，其可以包含许多拷贝的一种或多种治疗剂。 在更优选的实施方案中，聚合物可以与含有一种或多种半抗原如HSG的肽部分缀合。 药剂 - 聚合物 - 肽复合物可以通过例如利用双特异性或多特异性抗体或片段的预靶向技术递送至靶细胞，所述双特异性或多特异性抗体或片段具有识别半抗原的至少一个结合臂和至少一个结合的结合臂 具体涉及疾病或病原体相关抗原，例如肿瘤相关抗原。 提供了合成和使用这种治疗负载型聚合物及其共轭物的方法。
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5.发明申请Polymeric Carriers of Therapeutic Agents and Recognition Moieties for Antibody-Based Targeting of Disease Sites 有权治疗剂的聚合载体和用于基于抗体靶向疾病部位的识别部分公开(公告)号：US20100233779A1
公开(公告)日：2010-09-16
申请号：US12766092
申请日：2010-04-23
CPC分类号： A61K47/48315 , A61K31/4745 , A61K31/704 , A61K38/05 , A61K47/556 , A61K47/61 , A61K47/62 , A61K47/645 , A61K47/646 , A61K47/65 , A61K47/665 , A61K47/6951 , B82Y5/00 , C07K14/001 , C08B37/0021 , C08G83/003 , C08G83/004 , Y02A50/403
摘要： The present invention concerns methods and compositions for delivery of therapeutic agents to target cells, tissues or organisms. In preferred embodiments, the therapeutic agents are delivered in the form of therapeutic-loaded polymers that may comprise many copies of one or more therapeutic agents. In more preferred embodiments, the polymer may be conjugated to a peptide moiety that contains one or more haptens, such as HSG. The agent-polymer-peptide complex may be delivered to target cells by, for example, a pre-targeting technique utilizing bispecific or multispecific antibodies or fragments, having at least one binding arm that recognizes the hapten and at least a second binding arm that binds specifically to a disease or pathogen associated antigen, such as a tumor associated antigen. Methods for synthesizing and using such therapeutic-loaded polymers and their conjugates are provided.
摘要翻译： 本发明涉及用于将治疗剂递送至靶细胞，组织或生物体的方法和组合物。 在优选的实施方案中，治疗剂以治疗负荷聚合物的形式递送，其可以包含许多拷贝的一种或多种治疗剂。 在更优选的实施方案中，聚合物可以与含有一种或多种半抗原如HSG的肽部分缀合。 药剂 - 聚合物 - 肽复合物可以通过例如利用双特异性或多特异性抗体或片段的预靶向技术递送至靶细胞，所述双特异性或多特异性抗体或片段具有识别半抗原的至少一个结合臂和至少一个结合的结合臂 具体涉及疾病或病原体相关抗原，例如肿瘤相关抗原。 提供了合成和使用这种治疗负载型聚合物及其共轭物的方法。
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公开(公告)号：US09623115B2
公开(公告)日：2017-04-18
申请号：US13295647
申请日：2011-11-14
IPC分类号： A61K47/48 , C07K16/28 , A61K51/08 , C07K16/30 , C07K16/40 , C07K16/24 , B82Y5/00 , B82Y10/00 , B82Y30/00 , C07K16/00 , C07K16/44 , C07K16/46 , A61K39/00
CPC分类号： C07K16/2887 , A61K47/60 , A61K47/65 , A61K47/6813 , A61K47/6853 , A61K47/6891 , A61K2039/505 , B82Y5/00 , B82Y10/00 , B82Y30/00 , C07K16/00 , C07K16/2803 , C07K16/283 , C07K16/2833 , C07K16/2863 , C07K16/3007 , C07K16/44 , C07K16/468 , C07K2317/31 , C07K2317/55 , C07K2317/73 , C07K2317/732 , C07K2317/734 , C07K2319/00 , C07K2319/30 , C07K2319/70
摘要： Disclosed herein are compositions and methods of use of dock and lock (DNL) complexes comprising a first antibody or fragment that binds to a stem cell antigen and a second antibody or fragment thereof that binds to an antigen on a diseased or damaged tissue or organ. The DNL complexes are of use for targeting stem cells to diseased or damaged organs or tissues and may be used to treat a variety of diseases or conditions that are responsive to stem cell therapy.
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公开(公告)号：US08932593B2
公开(公告)日：2015-01-13
申请号：US13419614
申请日：2012-03-14
IPC分类号： C07K16/28 , C07K14/475 , C07K14/52 , C07K14/54 , C07K14/505 , C07K16/40 , B82Y5/00 , B82Y10/00 , C07K16/30
CPC分类号： C12N9/12 , B82Y5/00 , B82Y10/00 , C07K16/18 , C07K16/2803 , C07K16/2887 , C07K16/3007 , C07K16/3092 , C07K2317/31 , C07K2317/55 , C07K2319/00 , C07K2319/70 , C12Y207/11011
摘要： The present invention concerns methods and compositions for stably tethered structures of defined compositions, which may have multiple functionalities and/or binding specificities. Particular embodiments concern homodimers comprising monomers that contain a dimerization and docking domain attached to a precursor. The precursors may be virtually any molecule or structure, such as antibodies, antibody fragments, antibody analogs or mimetics, aptamers, binding peptides, fragments of binding proteins, known ligands for proteins or other molecules, enzymes, detectable labels or tags, therapeutic agents, toxins, pharmaceuticals, cytokines, interleukins, interferons, radioisotopes, proteins, peptides, peptide mimetics, polynucleotides, RNAi, oligosaccharides, natural or synthetic polymeric substances, nanoparticles, quantum dots, organic or inorganic compounds, etc. Other embodiments concern tetramers comprising a first and second homodimer, which may be identical or different. The disclosed methods and compositions provide a facile and general way to obtain homodimers, homotetramers and heterotetramers of virtually any functionality and/or binding specificity.
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8.发明授权Methods and compositions for generating bioactive assemblies of increased complexity and uses 有权用于生成增加复杂性和用途的生物活性组件的方法和组合物公开(公告)号：US08865176B2
公开(公告)日：2014-10-21
申请号：US13549906
申请日：2012-07-16
IPC分类号： C07K14/71 , C07K16/00 , C07K16/26 , C07K16/28 , A61K47/48 , A61K31/00 , B82Y10/00 , B82Y5/00 , C07K16/30 , G01N33/58 , B82Y15/00 , C12N9/96 , G01N33/543 , A61K38/00 , A61K39/00
CPC分类号： A61K47/48438 , A61K31/00 , A61K38/00 , A61K47/48415 , A61K47/48484 , A61K47/485 , A61K47/48538 , A61K47/48546 , A61K47/48561 , A61K47/48569 , A61K47/6811 , A61K47/6817 , A61K47/6829 , A61K47/6833 , A61K47/6843 , A61K47/6845 , A61K47/6849 , A61K47/6851 , A61K2039/505 , B82Y5/00 , B82Y10/00 , B82Y15/00 , C07K14/475 , C07K16/18 , C07K16/22 , C07K16/28 , C07K16/2803 , C07K16/2833 , C07K16/2851 , C07K16/2863 , C07K16/2881 , C07K16/2887 , C07K16/2896 , C07K16/3007 , C07K16/3092 , C07K16/32 , C07K2317/31 , C07K2317/55 , C07K2317/76 , C07K2319/30 , C07K2319/35 , C07K2319/70 , C07K2319/74 , C12N9/12 , C12N9/22 , C12N9/96 , C12Y207/11001 , G01N33/54353 , G01N33/588 , Y02A50/491
摘要： The present invention concerns methods and compositions for making and using bioactive assemblies of defined compositions, which may have multiple functionalities and/or binding specificities. In particular embodiments, the bioactive assembly is formed using dock-and-lock (DNL) methodology, which takes advantage of the specific binding interaction between dimerization and docking domains (DDD) and anchoring domains (AD) to form the assembly. In various embodiments, one or more effectors may be attached to a DDD or AD sequence. Complementary AD or DDD sequences may be attached to an adaptor module that forms the core of the bioactive assembly, allowing formation of the assembly through the specific DDD/AD binding interactions. Such assemblies may be attached to a wide variety of effector moieties for treatment, detection and/or diagnosis of a disease, pathogen infection or other medical or veterinary condition.
摘要翻译： 本发明涉及用于制备和使用具有多种功能和/或结合特异性的限定组合物的生物活性组合物的方法和组合物。 在特定的实施方案中，生物活性组件使用对接和锁定（DNL）方法形成，其利用二聚化和对接结构域（DDD）和锚定结构域（AD）之间的特异性结合相互作用形成组件。 在各种实施方案中，一个或多个效应物可以连接到DDD或AD序列。 互补AD或DDD序列可以连接到形成生物活性组件核心的适配器模块，从而允许通过特定的DDD / AD结合相互作用形成组装体。 这些组合物可以连接到各种各样的效应部分，用于治疗，检测和/或诊断疾病，病原体感染或其他医学或兽医病症。
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公开(公告)号：US20130177532A1
公开(公告)日：2013-07-11
申请号：US13589575
申请日：2012-08-20
CPC分类号： A61K47/6835 , A61K38/1816 , A61K38/193 , A61K38/212 , A61K47/60 , A61K47/65 , A61K47/6853 , A61K51/1048 , B82Y5/00 , B82Y10/00 , C07K2319/00 , C07K2319/70
摘要： The present invention concerns methods and compositions for forming PEGylated complexes of defined stoichiometry and structure. In preferred embodiments, the PEGylated complex is formed using dock-and-lock technology, by attaching a target agent to a DDD sequence and attaching a PEG moiety to an AD sequence and allowing the DDD sequence to bind to the AD sequence in a 2:1 stoichiometry, to form PEGylated complexes with two target agents and one PEG moiety. In alternative embodiments, the target agent may be attached to the AD sequence and the PEG to the DDD sequence to form PEGylated complexes with two PEG moieties and one target agent. In more preferred embodiments, the target agent may comprise any peptide or protein of physiologic or therapeutic activity. The PEGylated complexes exhibit a significantly slower rate of clearance when injected into a subject and are of use for treatment of a wide variety of diseases.
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10.发明授权Dimeric alpha interferon PEGylated site-specifically shows enhanced and prolonged efficacy in VIVO 有权二聚体α干扰素聚乙二醇化位点特异性显示VIVO中增强和延长的功效公开(公告)号：US08435540B2
公开(公告)日：2013-05-07
申请号：US13412816
申请日：2012-03-06
IPC分类号： A61K38/21 , C07K17/08 , C07K14/52 , C07K14/56 , C07K14/565
CPC分类号： C12N9/1205 , A61K39/395 , A61K47/60 , A61K47/64 , B82Y10/00 , B82Y30/00 , C07K16/00 , C07K16/005 , C07K16/283 , C07K16/3007 , C07K16/468 , C07K2317/31 , C07K2317/55 , C07K2317/73 , C07K2319/00 , C07K2319/70 , Y02A50/386
摘要： The present invention concerns methods and compositions for PEGylated complexes of defined stoichiometry and structure. Preferably, the PEGylated complex is formed using dock-and-lock technology, by attaching a therapeutic agent to a DDD sequence and a PEG moiety to an AD sequence, allowing the DDD sequence to bind to the AD sequence in a 2:1 stoichiometry, to form PEGylated complexes with two therapeutic agents and one PEG moiety. Alternatively, the therapeutic agent may be attached to the AD sequence and the PEG to the DDD sequence to form PEGylated complexes with two PEG moieties and one therapeutic agent. In more preferred embodiments, the therapeutic agent may comprise any peptide or protein of physiologic or therapeutic activity, preferably a cytokine, more preferably interferon-α2b. The PEGylated complexes exhibit a significantly slower rate of clearance when injected into a subject and are of use for treatment of a wide variety of diseases.
摘要翻译： 本发明涉及具有限定化学计量和结构的聚乙二醇化配合物的方法和组合物。 优选地，使用对接和锁定技术形成聚乙二醇化复合物，通过将治疗剂连接到AD序列和PEG部分到AD序列，允许DDD序列以2:1化学计量比结合AD序列， 以形成具有两个治疗剂和一个PEG部分的PEG化复合物。 或者，治疗剂可以连接到AD序列，并将PEG连接到DDD序列以形成具有两个PEG部分和一种治疗剂的聚乙二醇化复合物。 在更优选的实施方案中，治疗剂可以包含生理或治疗活性的任何肽或蛋白质，优选细胞因子，更优选干扰素-α2b。 当注射到受试者中时，聚乙二醇化复合物表现出明显较慢的清除率，并且可用于治疗各种各样的疾病。
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