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1. 发明申请

WO2018035424A1 BIFUNCTIONAL ANTIFUNGAL AGENTS AND METHODS OF TREATING FUNGAL INFECTION 审中-公开
标题翻译：双功能抗真菌药物和治疗真菌感染的方法
公开(公告)号：WO2018035424A1
公开(公告)日：2018-02-22
申请号：PCT/US2017/047536
申请日：2017-08-18
申请人： YALE UNIVERSITY , MERCK SHARP & DOHME CORP.
发明人： SPIEGEL, David, A. , CHIRKIN, Egor , ROEMER, Terry , NANTERMET, Philippe
IPC分类号： C07D403/12 , C07D251/68 , A61K31/53 , A61K31/10
CPC分类号： A61K31/53 , A61K31/10 , A61P31/10 , C07D251/68 , C07D403/12 , Y02P20/55
摘要： The present invention is directed to bifunctional compounds which are useful in the treatment of fungal infections. The present compounds contains at least one fungal binding moiety (FBM) which is linked to at least one antibody binding moiety (Α B Μ or ABT group) through a linker group, which optionally comprises a connector group. Compounds accordirig to the present invention are useful in the treatment of fungal infections as described herein.
摘要翻译：本发明涉及可用于治疗真菌感染的双功能化合物。本发明化合物含有至少一个真菌结合部分（FBM），其通过接头基团连接至至少一个抗体结合部分（AβB或MABT基团），所述接头基团任选地包含连接基团。符合本发明的化合物可用于治疗本文所述的真菌感染。

2. 发明申请

WO2014178878A1 SYNTHETIC ANTIBODY MIMETIC COMPOUNDS (SYAMS) TARGETING CANCER, ESPECIALLY PROSTATE CANCER 审中-公开
标题翻译：合成抗体化合物（SYAMS）靶向癌，特别是前列腺癌
公开(公告)号：WO2014178878A1
公开(公告)日：2014-11-06
申请号：PCT/US2013/039472
申请日：2013-05-03
申请人： YALE UNIVERSITY
发明人： SPIEGEL, David, A. , MCENANEY, Patrick , FITZGERALD, Kelly
IPC分类号： A61K39/395 , A61K38/16 , C07D249/04 , C07D403/10 , A61P35/00
CPC分类号： A61K47/481 , A61K31/194 , A61K38/10 , A61K45/06 , A61K47/55 , C07D249/04 , C07D249/06
摘要： The present invention relates to compounds which function as antibody mimetic compounds. These compounds are bifunctional/multifunctional compounds which contain at least one cancer cell binding moiety which selectively binds to prostate specific membrane antigen (PSMA) and a FC receptor binding moiety which modulates an FC immune receptor, preferably a FcγRI receptor. Compounds according to the present invention bind selectively to cancer cells which upregulate PSMA and through that interaction, place the Fc receptor binding moiety of the compound in proximity to a Fc receptor, preferably a FcγRI receptor, which can modulate (preferably, upregulate) a humoral response in a patient to cancer cells. Through this biological action of the compounds according to the present invention, cancer cells, including metastatic cancer cells, especially prostate cancer cells can be immune regulated, resulting in the favorable therapy of cancer in a patient. Methods of using these compounds to treat cancer and/or reduce the likelihood of metastatis of cancer are additional aspects of the present invention.
摘要翻译：本发明涉及作为抗体模拟化合物起作用的化合物。这些化合物是含有至少一个选择性结合前列腺特异性膜抗原（PSMA）的癌细胞结合部分和调节FC免疫受体，优选FcγRI受体的FC受体结合部分的双功能/多功能化合物。根据本发明的化合物选择性地结合上调PSMA的癌细胞，并通过该相互作用将化合物的Fc受体结合部分置于Fc受体（优选FcγRI受体）附近，该受体可调节（优选上调）体液患者对癌细胞的反应。通过本发明化合物的这种生物学作用，包括转移性癌细胞，特别是前列腺癌细胞在内的癌细胞可以被免疫调节，导致患者癌症的有利治疗。使用这些化合物治疗癌症和/或降低癌症转移可能性的方法是本发明的另外的方面。

3. 发明申请

WO2013070688A1 REPROGRAMMING UROKINASE INTO AN ANTIBODY-RECRUITING ANTICANCER AGENT 审中-公开
标题翻译：将尿激酶转化成抗体受体反应剂
公开(公告)号：WO2013070688A1
公开(公告)日：2013-05-16
申请号：PCT/US2012/063844
申请日：2012-11-07
申请人： YALE UNIVERSITY
发明人： SPIEGEL, David, A. , JAKOBSCHE, Charles, E.
IPC分类号： A61K31/47 , A61K31/496 , A61K31/155 , A61K31/16 , A61K31/08
CPC分类号： C12N9/96 , A61K31/165 , A61K31/352 , A61K31/365 , A61K38/05 , A61K38/482 , A61K45/06 , A61K47/54 , A61K47/60 , C07C279/12 , C07D491/107 , C07D493/10 , C07K5/06026 , A61K2300/00
摘要： The present invention relates to chimeric (preferably, bifunctional) compounds, compositions comprising those compounds and methods of treating cancer in a patient or subject, especially including metastatic cancer where cancer cells exhibit ovrexpression (heightened expression) of cell surface urokinase-type plasminogen activator receptor (urokinase receptor) compared to normal (non-cancerous) cells. The compounds preferably covalently bind to the urokinase receptor and recruit native antibodies of the patient or subject where the antibodies can selectively degrade and/or deactivate targeted cancer cells through antibody-dependent cellular phagocytosis and/or antibody-dependent cellular cytotoxicity (ADCC) against a large number and variety of cancers, thus providing cancer cell death and/or an inhibition of growth, elaboration and/or metastasis of the cancer, including remission and cure of the patient's cancer.
摘要翻译：本发明涉及嵌合（优选双官能）化合物，包含这些化合物的组合物和治疗患者或受试者中的癌症的方法，特别是包括转移性癌症，其中癌细胞表现出细胞表面尿激酶型纤溶酶原激活物受体的表达（高表达）（尿激酶受体）与正常（非癌性）细胞相比。化合物优选共价结合尿激酶受体并招募患者或受试者的天然抗体，其中抗体可以通过抗体依赖性细胞吞噬作用和/或抗体依赖性细胞毒性（ADCC）选择性降解和/或失活靶向癌细胞大量和多种癌症，从而提供癌细胞死亡和/或抑制癌症的生长，修复和/或转移，包括缓解和治愈患者的癌症。

4. 发明申请

WO2013166110A1 TLR-AGONIST-CONJUGATED ANTIBODY RECRUITING MOLECULES (TLR_ARMS) 审中-公开
标题翻译： TLR-激动剂联合抗体收集分子（TLR_ARMS）
公开(公告)号：WO2013166110A1
公开(公告)日：2013-11-07
申请号：PCT/US2013/039007
申请日：2013-05-01
申请人： YALE UNIVERSITY
发明人： SPIEGEL, David, A. , FITZGERALD, Kelly
IPC分类号： C07D471/04 , C07D473/02 , A61K31/437 , A61K39/44 , A61P35/00
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.
摘要翻译：本发明涉及用于向癌细胞，特别是前列腺癌细胞或转移前列腺癌细胞募集抗体的嵌合化合物。根据本发明的化合物包含通过接头和多功能连接基团或分子共价键合到细胞结合末端（CBT）和Toll样受体激动剂（TLR）的抗体结合末端（ABT）部分。

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