公开(公告)号：US10016412B2

公开(公告)日：2018-07-10

申请号：US15374272

申请日：2016-12-09

申请人： YALE UNIVERSITY

发明人： David Spiegel ,  Kelly Fitzgerald

IPC分类号： A61K31/56 ,  A61K31/4745 ,  A61K47/48 ,  C07D471/04

CPC分类号： A61K31/4745 ,  A61K31/53 ,  A61K45/06 ,  A61K47/60 ,  A61K47/66 ,  A61K47/6869 ,  A61K47/6897 ,  B82Y5/00 ,  C07D471/04 ,  C07K16/44 ,  C07K2317/732

摘要： The present invention relates to chimeric chemical compounds which are used to recruit antibodies to cancer cells, in particular, prostate cancer cells or metastasized prostate cancer cells. The compounds according to the present invention comprise an antibody binding terminus (ABT) moiety covalently bonded to a cell binding terminus (CBT) and Toll-like receptor agonist (TLR) through a linker and a multifunctional connector group or molecule.

公开(公告)号：US09913921B2

公开(公告)日：2018-03-13

申请号：US14115455

申请日：2012-05-07

申请人： Marc Stefan Robillard ,  Johan Lub ,  Raffaella Rossin ,  Sandra Martina Van Ben Bosch ,  Ronny Mathieu Versteegen

发明人： Marc Stefan Robillard ,  Johan Lub ,  Raffaella Rossin ,  Sandra Martina Van Ben Bosch ,  Ronny Mathieu Versteegen

IPC分类号： A61K51/10 ,  A61K51/04 ,  B82Y5/00 ,  C07D207/46 ,  C07D235/02 ,  C07D245/02 ,  C07D249/16 ,  A61K47/68 ,  A61K49/10

CPC分类号： A61K51/1093 ,  A61K47/6897 ,  A61K49/106 ,  A61K51/041 ,  A61K51/0495 ,  A61K51/0497 ,  B82Y5/00 ,  C07D207/46 ,  C07D235/02 ,  C07D245/02 ,  C07D249/16

摘要： Described is a pretargeting method, and related kits, for targeted medical imaging and/or therapeutics, wherein use is made of abiotic reactive chemical groups that exhibit bio-orthogonal reactivity towards each other. The invention involves the use of [4+2] inverse electron demand (retro) Diels-Alder chemistry in providing the coupling between a Pre-targeting Probe and an Effector Probe. To this end one of these probes comprises an electron-deficient tetrazine or other suitable diene, and the other an E-cyclooctene which has a flattened structure as a result of the position of at least two exocyclic bonds.

公开(公告)号：US20170088635A1

公开(公告)日：2017-03-30

申请号：US15366629

申请日：2016-12-01

申请人： IBC Pharmaceuticals, Inc.

发明人： Chien-Hsing Chang ,  David M. Goldenberg

IPC分类号： C07K16/46 ,  C07K16/18 ,  C07K16/28 ,  C07K16/30 ,  A61K39/39 ,  A61K31/713 ,  A61K38/46 ,  A61K39/00 ,  A61K39/275 ,  A61K51/10 ,  C07K16/24

CPC分类号： C07K16/468 ,  A61K38/465 ,  A61K39/0011 ,  A61K39/39 ,  A61K47/6897 ,  A61K2039/505 ,  C07K16/18 ,  C07K16/243 ,  C07K16/249 ,  C07K16/2833 ,  C07K16/2851 ,  C07K16/2863 ,  C07K16/2887 ,  C07K16/30 ,  C07K16/3007 ,  C07K16/3092 ,  C07K2317/31 ,  C07K2317/35

摘要： Disclosed herein are methods and compositions dock and lock (DNL) complexes comprising an AD moiety selected from an AKAP protein and a DDD moiety selected from a protein kinase A regulatory subunit. Also disclosed are fusion proteins comprising an AD moiety or DDD moiety attached to an effector moiety. The DDD moieties form dimers that bind to the AD moiety to form the DNL complexes. The effector moieties may be selected from a wide range of known effector moieties that produce one or more physiological effects, including but not limited to cell death. The DNL complexes may further comprise one or more diagnostic and/or therapeutic agents. The DNL complexes are of use for treating and/or diagnosing a variety of diseases or conditions.

公开(公告)号：US20170087148A1

公开(公告)日：2017-03-30

申请号：US15374272

申请日：2016-12-09

申请人： YALE UNIVERSITY

发明人： David Spiegel ,  Kelly Fitzgerald

IPC分类号： A61K31/4745 ,  C07D471/04

CPC分类号： A61K31/4745 ,  A61K31/53 ,  A61K45/06 ,  A61K47/60 ,  A61K47/66 ,  A61K47/6869 ,  A61K47/6897 ,  B82Y5/00 ,  C07D471/04 ,  C07K16/44 ,  C07K2317/732

摘要： The present invention relates to chimeric chemical compounds which are used to recruit antibodies to cancer cells, in particular, prostate cancer cells or metastasized prostate cancer cells. The compounds according to the present invention comprise an antibody binding terminus (ABT) moiety covalently bonded to a cell binding terminus (CBT) and Toll-like receptor agonist (TLR) through a linker and a multifunctional connector group or molecule.

公开(公告)号：US09513293B2

公开(公告)日：2016-12-06

申请号：US14944993

申请日：2015-11-18

申请人： Immunomedics, Inc.

发明人： David V. Gold ,  David M. Goldenberg

IPC分类号： A61K39/395 ,  G01N33/574 ,  A61K47/48 ,  A61K51/04 ,  A61K51/08 ,  A61K51/10 ,  B82Y5/00 ,  B82Y15/00 ,  C07K16/30 ,  C07K16/44 ,  A61K39/00

CPC分类号： A61K47/48746 ,  A61K47/6897 ,  A61K49/0058 ,  A61K51/0406 ,  A61K51/0491 ,  A61K51/08 ,  A61K51/088 ,  A61K51/1018 ,  A61K51/109 ,  A61K2039/505 ,  A61K2039/507 ,  B82Y5/00 ,  B82Y15/00 ,  C07K16/303 ,  C07K16/3092 ,  C07K16/44 ,  C07K2317/24 ,  C07K2317/31 ,  C07K2317/54 ,  C07K2317/55 ,  C07K2317/565 ,  G01N33/57438 ,  G01N33/57488 ,  G01N2333/4725

摘要： Described herein are compositions and methods of use of anti-pancreatic cancer antibodies or fragments thereof, such as murine, chimeric, humanized or human PAM4 antibodies. The subject antibodies show a number of novel and useful diagnostic characteristics, such as binding with high specificity to pancreatic and other cancers, but not to normal pancreatic tissues and binding to a high percentage of early stage pancreatic cancers. In preferred embodiments, the antibodies bind to pancreatic cancer mucins. The antibodies and fragments are of use for the detection and diagnosis of early stage pancreatic cancer. In preferred embodiments, the anti-pancreatic cancer antibodies can be used for immunoassay of serum samples, wherein the immunoassay can detect a marker for early stage pancreatic cancer in serum. More preferably, the serum is extracted with an organic phase, such as butanol, before immunoassay.

公开(公告)号：US20160257947A9

公开(公告)日：2016-09-08

申请号：US14017885

申请日：2013-09-04

申请人： IBC PHARMACEUTICALS, INC. ,  IMMUNOMEDICS, INC.

发明人： Chien-Hsing Chang ,  David M. Goldenberg ,  Edmund A. Rossi

IPC分类号： C12N9/96

CPC分类号： A61K38/465 ,  A61K39/0011 ,  A61K39/39558 ,  A61K45/06 ,  A61K47/62 ,  A61K47/646 ,  A61K47/6897 ,  A61K51/088 ,  A61K51/1027 ,  A61K2039/505 ,  A61K2039/6056 ,  A61K2039/625 ,  B82Y5/00 ,  C07K16/2803 ,  C07K16/2833 ,  C07K16/2887 ,  C07K16/30 ,  C07K16/3007 ,  C07K16/468 ,  C07K2317/24 ,  C07K2317/31 ,  C07K2317/522 ,  C07K2317/524 ,  C07K2317/526 ,  C07K2317/55 ,  C07K2317/565 ,  C07K2317/567 ,  C07K2317/622 ,  C07K2317/76 ,  C07K2317/77 ,  C07K2317/92 ,  C07K2319/00 ,  C07K2319/30 ,  C12N9/96 ,  C12Y207/11011 ,  C12Y301/27

摘要： The present invention concerns methods and compositions for forming immunotoxin complexes having a high efficacy and low systemic toxicity. In preferred embodiments, the toxin moiety is a ranpirnase (Rap), such as Rap(Q). In more preferred embodiments, the immunotoxin is made using dock-and-lock (DNL) technology. The immunotoxin exhibits improved pharmacokinetics, with a longer serum half-life and significantly greater efficacy compared to toxin alone, antibody alone, unconjugated toxin plus antibody or even other types of toxin-antibody constructs. In a most preferred embodiment the construct comprises an anti-Trop-2 antibody conjugated to Rap, although other combinations of antibodies, antibody fragments and toxins may be used to form the subject immunotoxins. The immunotoxins are of use to treat a variety of diseases, such as cancer, autoimmune disease or immune dysfunction.

公开(公告)号：US09428553B2

公开(公告)日：2016-08-30

申请号：US13764762

申请日：2013-02-11

申请人： City of Hope

发明人： John C. Williams ,  Cindy Zer ,  Krzysztof Bzymek ,  Kendra Nicole Avery

IPC分类号： A61K38/00 ,  C07K14/00 ,  A61K47/48 ,  C07K16/28 ,  C07K16/32 ,  B82Y5/00

CPC分类号： C07K14/001 ,  A61K47/48346 ,  A61K47/48746 ,  A61K47/66 ,  A61K47/6897 ,  B82Y5/00 ,  C07K16/2863 ,  C07K16/32 ,  C07K2299/00 ,  C07K2317/34 ,  C07K2317/55 ,  C07K2317/567 ,  C07K2317/622 ,  C07K2317/92

摘要： Antibodies and meditopes that bind to the antibodies are provided, as well as complexes, compositions and combinations containing the meditopes and antibodies, and methods of producing, using, testing, and screening the same, including therapeutic and diagnostic methods and uses.

公开(公告)号：US09421274B2

公开(公告)日：2016-08-23

申请号：US14117246

申请日：2012-05-16

申请人： Marc Stefan Robillard ,  Hendricus Marie Janssen ,  Wolter Ten Hoeve ,  Ronny Mathieu Versteegen

发明人： Marc Stefan Robillard ,  Hendricus Marie Janssen ,  Wolter Ten Hoeve ,  Ronny Mathieu Versteegen

IPC分类号： C07D257/08 ,  C07D237/26 ,  C07C13/263 ,  C07C33/16 ,  A61K31/435 ,  A61K31/502 ,  A61K31/045 ,  A61K47/48 ,  B82Y5/00

CPC分类号： A61K47/6803 ,  A61K31/435 ,  A61K31/444 ,  A61K31/704 ,  A61K38/05 ,  A61K39/3955 ,  A61K39/39558 ,  A61K47/22 ,  A61K47/545 ,  A61K47/555 ,  A61K47/558 ,  A61K47/6897 ,  B82Y5/00 ,  C07C33/16 ,  C07D237/26 ,  C07D257/08 ,  Y02A50/471

摘要： The invention relates to a Prodrug activation method, for therapeutics, wherein use is made of abiotic reactive chemical groups that exhibit bio-orthogonal reactivity towards each other. The invention also relates to a Prodrug kit comprising at least one Prodrug and at least one Activator, wherein the Prodrug comprises a Drug and a first Bio-orthogonal Reactive Group (the Trigger), and wherein the Activator comprises a second Bio-orthogonal Reactive Group. The invention also relates to targeted therapeutics used in the above-mentioned method and kit. The invention particularly pertains to antibody-drug conjugates and to bi- and trispecific antibody derivatives.

摘要翻译： 本发明涉及用于治疗剂的前药活化方法，其中使用对彼此具有生物正交反应性的非生物活性化学基团。 本发明还涉及包含至少一种前药和至少一种活化剂的前药盒，其中所述前药包含药物和第一生物正交反应性组（所述触发剂），并且其中所述活化剂包含第二生物正交反应性组 。 本发明还涉及上述方法和试剂盒中使用的靶向治疗剂。 本发明特别涉及抗体 - 药物偶联物和双特异性和三特异性抗体衍生物。

公开(公告)号：US20160130356A1

公开(公告)日：2016-05-12

申请号：US14987432

申请日：2016-01-04

申请人： Siamab Therapeutics, Inc.

发明人： Julie DeSander ,  Jeffrey Behrens

IPC分类号： C07K16/30 ,  A61K39/395 ,  A61K47/02 ,  A61K47/48 ,  A61K47/12

CPC分类号： C07K16/30 ,  A61K9/0019 ,  A61K39/39558 ,  A61K39/39591 ,  A61K47/02 ,  A61K47/12 ,  A61K47/6803 ,  A61K47/6851 ,  A61K47/6897 ,  A61K2039/505 ,  C07K16/44 ,  C07K2317/33 ,  C07K2317/622 ,  C07K2317/73 ,  C07K2317/732 ,  C07K2317/92

摘要： The present invention provides glycan-interacting antibodies and methods for producing glycan-interacting antibodies useful in the treatment and prevention of human disease, including cancer. Such glycan-interacting antibodies include monoclonal antibodies, derivatives, and fragments thereof as well as compositions and kits comprising them. Further provided are methods of using glycan-interacting antibodies to target cells and treat disease.

摘要翻译： 本发明提供了聚糖相互作用的抗体和用于生产可用于治疗和预防人类疾病（包括癌症）的聚糖相互作用的抗体的方法。 这样的聚糖相互作用抗体包括单克隆抗体，衍生物及其片段，以及包含它们的组合物和试剂盒。 还提供了使用聚糖相互作用抗体靶向细胞并治疗疾病的方法。

公开(公告)号：US20160082102A1

公开(公告)日：2016-03-24

申请号：US14883959

申请日：2015-10-15

申请人： YALE UNIVERSITY

发明人： David Spiegel ,  Christopher Parker

IPC分类号： A61K39/385 ,  A61K9/00 ,  A61K47/48 ,  A61K45/06

CPC分类号： A61K39/385 ,  A61K9/0019 ,  A61K9/0053 ,  A61K31/4745 ,  A61K45/06 ,  A61K47/545 ,  A61K47/6897 ,  A61K2039/54 ,  A61K2039/57 ,  A61K2039/58 ,  A61K2039/6012 ,  A61K2039/627 ,  B82Y5/00 ,  C07D403/12 ,  C07D405/04 ,  C07D405/14 ,  C07D471/04 ,  A61K2300/00

摘要： The present invention is directed to new bifunctional compounds and methods for treating HIV infections. The bifunctional small molecules, generally referred to as ARM-H's, function through orthogonal pathways, by inhibiting the gp120-CD4 interaction, and by recruiting anti-DNP antibodies to gp120-expressing cells, thereby preventing cell infection and spread of HIV. It has been shown that ARM-H's bind to gp120 and gp-120 expressing cells competitively with CD4, thereby decreasing viral infectivity as shown by an MT-2 cell assay, the binding leading to formation of a ternary complex by recruiting anti-DNP antibodies to bind thereto, the antibodies present in the ternary complex promoting the complement-dependent destruction of the gp120-expressing cells. Compounds and methods are described herein.

摘要翻译： 本发明涉及新的双功能化合物和用于治疗HIV感染的方法。 通常称为ARM-H的双官能小分子通过正交途径通过抑制gp120-CD4相互作用和通过向表达gp120的细胞募集抗DNP抗体，从而防止细胞感染和HIV的扩散而起作用。 已经表明，ARM-H与gp120和gp-120表达细胞结合，与CD4竞争性，从而降低病毒感染性，如MT-2细胞测定所示，通过募集抗DNP抗体导致形成三元复合物的结合 与其结合，存在于三元复合物中的抗体促进表达gp120的细胞的补体依赖性破坏。 本文描述了化合物和方法。