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    COMPOUNDS AND METHODS FOR KINASE MODULATION, AND INDICATIONS THEREFOR
    1.
    发明申请
    COMPOUNDS AND METHODS FOR KINASE MODULATION, AND INDICATIONS THEREFOR 有权
    化合物及其调节方法及其适应症

    公开(公告)号：US20110263595A1

    公开(公告)日：2011-10-27

    申请号：US13090969

    申请日：2011-04-20

    申请人： Jiazhong Zhang ,  Prabha N. Ibrahim ,  Wayne Spevak ,  James Tsai ,  Todd Ewing ,  Ying Zhang ,  Chao Zhang

    发明人： Jiazhong Zhang ,  Prabha N. Ibrahim ,  Wayne Spevak ,  James Tsai ,  Todd Ewing ,  Ying Zhang ,  Chao Zhang

    IPC分类号： A61K31/5377 ,  A61K31/506 ,  A61K31/437 ,  C07D487/04 ,  A61K31/519 ,  C07D413/14 ,  A61P19/02 ,  A61P19/10 ,  A61P9/00 ,  A61P25/00 ,  A61P25/28 ,  A61P29/00 ,  A61P35/00 ,  A61P1/00 ,  C07D471/04

    CPC分类号： C07D487/04 ,  C07D471/04

    摘要： Compounds and salts thereof, formulations thereof, conjugates thereof, derivatives thereof, forms thereof and uses thereof are described. In certain aspects and embodiments, the described compounds or salts thereof, formulations thereof, conjugates thereof, derivatives thereof, forms thereof are active on one or more of Fms, Kit, Flt3, TrkA, TrkB and TrkC kinase protein. Also described are methods of use thereof to treat diseases and conditions, including diseases and conditions associated with activity of one or more of Fms, Kit, Flt3, TrkA, TrkB and TrkC, including rheumatoid arthritis, osteoarthritis, osteoporosis, peri-prosthetic osteolysis, systemic sclerosis, demyelinating disorders, multiple sclerosis, Charcot Marie Tooth syndrome, amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's disease, global ischemia, ulcerative colitis, Crohn's disease, immune thrombocytopenic purpura, atherosclerosis, systemic lupus erythematosis, myelopreparation for autologous transplantation, transplant rejection, glomerulonephritis, interstitial nephritis, Lupus nephritis, tubular necrosis, diabetic nephropathy, renal hypertrophy, type I diabetes, acute pain, inflammatory pain, neuropathic pain, acute myeloid leukemia, melanoma, multiple myeloma, breast cancer, prostate cancer, pancreatic cancer, lung cancer, ovarian cancer, gliomas, glioblastoma, neurofibromatosis, osteolytic bone metastases, brain metasteses, gastrointestinal stromal tumors, and giant cell tumors.

    摘要翻译： 其化合物及其盐，其制剂，其缀合物，其衍生物，其形式及用途。 在某些方面和实施方案中，所述的化合物或其盐，其制剂，其缀合物，其衍生物，其形式在Fms，Kit，Flt3，TrkA，TrkB和TrkC激酶蛋白中的一种或多种上是有活性的。 还描述了其用于治疗疾病和病症的方法，包括与Fms，Kit，Flt3，TrkA，TrkB和TrkC中的一种或多种的活性相关的疾病和病症，包括类风湿性关节炎，骨关节炎，骨质疏松症，假体周围骨质溶解， 系统性硬化症，脱髓鞘疾病，多发性硬化症，Charcot玛丽牙综合征，肌萎缩性侧索硬化症，阿尔茨海默氏病，帕金森病，全球缺血，溃疡性结肠炎，克罗恩病，免疫性血小板减少性紫癜，动脉粥样硬化，系统性红斑狼疮，自体移植骨髓移植，移植排斥 肾小球肾炎，间质性肾炎，狼疮性肾炎，肾小管坏死，糖尿病性肾病，肾肥大，I型糖尿病，急性疼痛，炎性疼痛，神经性疼痛，急性骨髓性白血病，黑素瘤，多发性骨髓瘤，乳腺癌，前列腺癌，胰腺癌，肺癌 癌症，卵巢癌，神经胶质瘤，胶质母细胞瘤，神经元 骨质疏松症，溶骨性骨转移，脑转移，胃肠道间质瘤和巨细胞肿瘤。

    Compounds and methods for kinase modulation, and indications therefor
    2.
    发明授权
    Compounds and methods for kinase modulation, and indications therefor 有权
    用于激酶调节的化合物和方法及其适应症

    公开(公告)号：US08901118B2

    公开(公告)日：2014-12-02

    申请号：US13090969

    申请日：2011-04-20

    申请人： Jiazhong Zhang ,  Prabha N. Ibrahim ,  Wayne Spevak ,  Jianming Tsai ,  Todd Ewing ,  Ying Zhang ,  Chao Zhang

    发明人： Jiazhong Zhang ,  Prabha N. Ibrahim ,  Wayne Spevak ,  Jianming Tsai ,  Todd Ewing ,  Ying Zhang ,  Chao Zhang

    IPC分类号： C07D487/04 ,  A61K31/519 ,  C07D471/04 ,  A61P19/02 ,  A61P19/10 ,  A61P25/28 ,  A61P29/00 ,  A61K31/437

    CPC分类号： C07D487/04 ,  C07D471/04

    摘要： Compounds and salts thereof, formulations thereof, conjugates thereof, derivatives thereof, forms thereof and uses thereof are described, wherein the compounds have formula I: In certain aspects and embodiments, the described compounds or salts thereof, formulations thereof, conjugates thereof, derivatives thereof, forms thereof are active on one or more of Fms, Kit, Flt3, TrkA, TrkB and TrkC kinase protein. Also described are methods of use thereof to treat diseases and conditions, including diseases and conditions associated with activity of one or more of Fms, Kit, Flt3, TrkA, TrkB and TrkC, including rheumatoid arthiritis, osteoarthritis, osteoporosis, peri-prosthetic osteolysis, systemic sclerosis, demyelinating disorders, multiple sclerosis, Charcot Marie Tooth syndrome, amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's disease, global ischemia, ulcerative colitis, Crohn's disease, immune thrombocytopenic purpura, atherosclerosis, systemic lupus erythematosis, myelopreparation for autologous transplantation, transplant rejection, glomerulonephritis, interstitial nephritis, Lupus nephritis, tubular necrosis, diabetic nephropathy, renal hypertrophy, type I diabetes, acute pain, inflammatory pain, neuropathic pain, acute myeloid leukemia, melanoma, multiple myeloma, breast cancer, prostate cancer, pancreatic cancer, lung cancer, ovarian cancer, gliomas, glioblastoma, neurofibromatosis, osteolytic bone metastases, brain metasteses, gastrointestinal stromal tumors, and giant cell tumors.

    摘要翻译： 描述了其化合物和盐，其制剂，其缀合物，其衍生物，其形式及其用途，其中所述化合物具有式I：在某些方面和实施方案中，所述的化合物或其盐，其制剂，其缀合物，其衍生物 其形式在Fms，Kit，Flt3，TrkA，TrkB和TrkC激酶蛋白中的一种或多种上是有活性的。 还描述了其用于治疗疾病和病症的方法，包括与Fms，Kit，Flt3，TrkA，TrkB和TrkC中的一种或多种的活性相关的疾病和病症，包括类风湿性关节炎，骨关节炎，骨质疏松症，假体周围骨质溶解， 系统性硬化症，脱髓鞘疾病，多发性硬化症，Charcot玛丽牙综合征，肌萎缩性侧索硬化症，阿尔茨海默氏病，帕金森病，全球缺血，溃疡性结肠炎，克罗恩病，免疫性血小板减少性紫癜，动脉粥样硬化，系统性红斑狼疮，自体移植骨髓移植，移植排斥 肾小球肾炎，间质性肾炎，狼疮性肾炎，肾小管坏死，糖尿病性肾病，肾肥大，I型糖尿病，急性疼痛，炎性疼痛，神经性疼痛，急性骨髓性白血病，黑素瘤，多发性骨髓瘤，乳腺癌，前列腺癌，胰腺癌，肺癌 癌症，卵巢癌，神经胶质瘤，成胶质细胞瘤，神经 纤维瘤病，溶骨性骨转移，脑转移，胃肠道间质瘤和巨细胞瘤。

    Compounds and methods for kinase modulation, and indications therefor
    5.
    发明授权
    Compounds and methods for kinase modulation, and indications therefor 有权
    用于激酶调节的化合物和方法及其适应症

    公开(公告)号：US08673928B2

    公开(公告)日：2014-03-18

    申请号：US12949741

    申请日：2010-11-18

    申请人： Prabha N. Ibrahim ,  Wayne Spevak ,  Hanna Cho ,  Songyuan Shi ,  Chao Zhang ,  Ying Zhang

    发明人： Prabha N. Ibrahim ,  Wayne Spevak ,  Hanna Cho ,  Songyuan Shi ,  Chao Zhang ,  Ying Zhang

    IPC分类号： C07D487/04 ,  A61K31/519 ,  A61P25/28 ,  A61P25/16 ,  A61P35/00 ,  A61P37/06 ,  A61P31/18

    CPC分类号： C07D487/04 ,  A61K31/437 ,  A61K31/519 ,  A61K31/5377 ,  C07D401/04 ,  C07D403/04 ,  C07D471/04

    摘要： and salts thereof, formulations thereof, conjugates thereof, derivatives thereof, forms thereof and uses thereof are described. In certain aspects and embodiments, the described compounds of Formula (I) or salts thereof, formulations thereof, conjugates thereof, derivatives thereof, forms thereof are active on at least one Raf protein kinase. In certain aspects and embodiments, the described compounds are active in inhibiting proliferation of a Ras mutant cell line. Also described are methods of use thereof to treat diseases and conditions, including diseases and conditions associated with activity of B-Raf V600E mutant protein kinase, including melanoma, glioma, glioblastoma multiforme, pilocytic astrocytoma, colorectal cancer, thyroid cancer, lung cancer, ovarian cancer, prostate cancer, liver cancer, gallbladder cancer, gastrointestinal stromal tumors, biliary tract cancer, and cholangiocarcinoma. Also described are methods of use thereof to treat diseases and conditions, including diseases and conditions associated with activity of c-Raf-1 protein kinase, including acute pain, chronic pain or polycystic kidney disease.

    摘要翻译： 及其盐，其制剂，其缀合物，其衍生物，其形式及用途。 在某些方面和实施方案中，所述式（I）化合物或其盐，其制剂，其缀合物，其衍生物，其形式在至少一种Raf蛋白激酶上具有活性。 在某些方面和实施方案中，所述化合物在抑制Ras突变细胞系的增殖中是有活性的。 还描述了其用于治疗疾病和病症的方法，包括与B-Raf V600E突变蛋白激酶（包括黑素瘤，神经胶质瘤，多形性成胶质细胞瘤，纤维细胞性星形细胞瘤，结肠直肠癌，甲状腺癌，肺癌，卵巢）的活动相关的疾病和病症 癌症，前列腺癌，肝癌，胆囊癌，胃肠道间质瘤，胆道癌和胆管癌。 还描述了其用于治疗疾病和病症的方法，包括与c-Raf-1蛋白激酶的活性相关的疾病和病症，包括急性疼痛，慢性疼痛或多囊肾病。

    Compounds and Methods for Kinase Modulation, and Indications Therefor
    6.
    发明申请
    Compounds and Methods for Kinase Modulation, and Indications Therefor 有权
    化合物和激酶调节方法及其适应症

    公开(公告)号：US20110152258A1

    公开(公告)日：2011-06-23

    申请号：US12949741

    申请日：2010-11-18

    申请人： Prabha N. Ibrahim ,  Wayne Spevak ,  Hanna Cho ,  Songyuan Shi ,  Chao Zhang ,  Ying Zhang

    发明人： Prabha N. Ibrahim ,  Wayne Spevak ,  Hanna Cho ,  Songyuan Shi ,  Chao Zhang ,  Ying Zhang

    IPC分类号： A61K31/5377 ,  C07D487/04 ,  A61K31/519 ,  C07D413/14 ,  C07D471/04 ,  A61K31/437 ,  A61P9/00 ,  A61P35/00 ,  A61P25/28 ,  A61P1/16 ,  A61P25/16 ,  A61P13/12 ,  A61P29/00 ,  A61P21/00

    CPC分类号： C07D487/04 ,  A61K31/437 ,  A61K31/519 ,  A61K31/5377 ,  C07D401/04 ,  C07D403/04 ,  C07D471/04

    摘要： Compounds and salts thereof, formulations thereof, conjugates thereof, derivatives thereof, forms thereof and uses thereof are described. In certain aspects and embodiments, the described compounds or salts thereof, formulations thereof, conjugates thereof, derivatives thereof, forms thereof are active on at least one Raf protein kinase. In certain aspects and embodiments, the described compounds are active in inhibiting proliferation of a Ras mutant cell line. Also described are methods of use thereof to treat diseases and conditions, including diseases and conditions associated with activity of B-Raf V600E mutant protein kinase, including melanoma, glioma, glioblastoma multiforme, pilocytic astrocytoma, colorectal cancer, thyroid cancer, lung cancer, ovarian cancer, prostate cancer, liver cancer, gallbladder cancer, gastrointestinal stromal tumors, biliary tract cancer, and cholangiocarcinoma. Also described are methods of use thereof to treat diseases and conditions, including diseases and conditions associated with activity of c-Raf-1 protein kinase, including acute pain, chronic pain or polycystic kidney disease.

    摘要翻译： 其化合物及其盐，其制剂，其缀合物，其衍生物，其形式及用途。 在某些方面和实施方案中，所述的化合物或其盐，其制剂，其缀合物，其衍生物，其形式在至少一种Raf蛋白激酶上具有活性。 在某些方面和实施方案中，所述化合物在抑制Ras突变细胞系的增殖中是有活性的。 还描述了其用于治疗疾病和病症的方法，包括与B-Raf V600E突变蛋白激酶（包括黑素瘤，神经胶质瘤，多形性成胶质细胞瘤，纤维细胞性星形细胞瘤，结肠直肠癌，甲状腺癌，肺癌，卵巢）的活动相关的疾病和病症 癌症，前列腺癌，肝癌，胆囊癌，胃肠道间质瘤，胆道癌和胆管癌。 还描述了其用于治疗疾病和病症的方法，包括与c-Raf-1蛋白激酶的活性相关的疾病和病症，包括急性疼痛，慢性疼痛或多囊肾病。

    RECOMBINANT ANTIBODIES TO PROGRAMMED DEATH 1 (PD-1) AND USES THEREFOR
    8.
    发明申请
    RECOMBINANT ANTIBODIES TO PROGRAMMED DEATH 1 (PD-1) AND USES THEREFOR 审中-公开

    公开(公告)号：US20200062847A1

    公开(公告)日：2020-02-27

    申请号：US16488667

    申请日：2017-03-04

    申请人： Ying ZHANG ,  Xiangtan Tenghua Bioscience

    发明人： Ying Zhang

    IPC分类号： C07K16/28

    摘要： Provided are monoclonal antibody, particularly rabbit recombinant antibody, which specifically binds to human PD-1 with biological functions and super high affinity, and methods of use. In various embodiments, the antibodies are fully humanized antibodies that bind to human PD-1. Nucleic acid molecules encoding the antibodies and methods for expressing the antibodies are also provided. In some embodiments, the antibodies are useful for inhibiting or neutralizing PD-1 activity, thus providing a means of treating, preventing and/or diagnosing a disease or disorder such as cancer or a viral infection.