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    Substituted heterocyclic compounds and methods of use
    32.
    发明授权
    Substituted heterocyclic compounds and methods of use 失效
    取代的杂环化合物及其使用方法

    公开(公告)号：US07504403B2

    公开(公告)日：2009-03-17

    申请号：US11041151

    申请日：2005-01-21

    Applicant: Michael J. Frohn ,  Fang-Tsao Hong ,  Longbin Liu ,  Patricia Lopez ,  Aaron Siegmund ,  Seifu Tadesse ,  Nuria Tamayo

    Inventor： Michael J. Frohn ,  Fang-Tsao Hong ,  Longbin Liu ,  Patricia Lopez ,  Aaron Siegmund ,  Seifu Tadesse ,  Nuria Tamayo

    IPC: C07D487/04 ,  A61K31/506

    CPC classification number: C07D487/04 ,  C07D471/04

    Abstract: The present invention relates to pyrimidinones and pyridones and derivatives thereof, and pharmaceutically acceptable salts thereof. Also included is a method of treatment of inflammation, rheumatoid arthritis, Pagets disease, osteoporosis, multiple myeloma, uveititis, acute or chronic myelogenous leukemia, pancreatic β cell destruction, osteoarthritis, rheumatoid spondylitis, gouty arthritis, inflammatory bowel disease, adult respiratory distress syndrome (ARDS), psoriasis, Crohn's disease, allergic rhinitis, ulcerative colitis, anaphylaxis, contact dermatitis, asthma, muscle degeneration, cachexia, Reiter's syndrome, type I diabetes, type II diabetes, bone resorption diseases, graft vs. host reaction, Alzheimer's disease, stroke, myocardial infarction, ischemia reperfusion injury, atherosclerosis, brain trauma, multiple sclerosis, cerebral malaria, sepsis, septic shock, toxic shock syndrome, fever, myalgias due to HIV-1, HIV-2, HIV-3, cytomegalovirus (CMV), influenza, adenovirus, the herpes viruses or herpes zoster infection in a mammal comprising administering an effective amount a compound as described above.

    Abstract translation: 本发明涉及嘧啶酮和吡啶酮及其衍生物及其药学上可接受的盐。 还包括治疗炎症，类风湿性关节炎，斑节病，骨质疏松症，多发性骨髓瘤，葡萄膜炎，急性或慢性骨髓性白血病，胰腺β细胞破坏，骨关节炎，类风湿性脊椎炎，痛风性关节炎，炎性肠病，成人呼吸窘迫综合征 （ARDS），牛皮癣，克罗恩病，过敏性鼻炎，溃疡性结肠炎，过敏反应，接触性皮炎，哮喘，肌肉变性，恶病质，赖特综合征，I型糖尿病，II型糖尿病，骨吸收疾病，移植物抗宿主反应，阿尔茨海默病 ，中风，心肌梗塞，缺血再灌注损伤，动脉粥样硬化，脑外伤，多发性硬化，脑疟疾，败血症，败血性休克，中毒性休克综合征，发热，HIV-1，HIV-2，HIV-3，巨细胞病毒 ），流感病毒，腺病毒，哺乳动物中的疱疹病毒或带状疱疹感染，包括给予有效量的如上所述的化合物。

    Recombinant human EPO-Fc fusion proteins with prolonged half-life and enhanced erythropoietic activity in vivo
    33.
    发明申请
    Recombinant human EPO-Fc fusion proteins with prolonged half-life and enhanced erythropoietic activity in vivo 有权
    重组人EPO-Fc融合蛋白具有延长的半衰期和增强体内红细胞生成活性

    公开(公告)号：US20070178112A1

    公开(公告)日：2007-08-02

    申请号：US11340661

    申请日：2006-01-27

    Applicant: Haitao Wang ,  Yong Du ,  Rui Zhang ,  Jing Xu ,  Longbin Liu

    Inventor： Haitao Wang ,  Yong Du ,  Rui Zhang ,  Jing Xu ,  Longbin Liu

    IPC: A61K39/395 ,  C12P21/06 ,  C07K16/46 ,  C07H21/04 ,  C12N5/06

    CPC classification number: C07K14/505 ,  A61K9/0019 ,  A61K38/00 ,  A61K47/6811 ,  C07K2317/53 ,  C07K2319/30

    Abstract: A recombinant fusion protein comprising a human erythropoietin peptide portion linked to an immunoglobulin peptide portion is described. The fusion protein has a prolonged half-life in vivo in comparison to naturally occurring or recombinant native human erythropoietin. In one embodiment of the invention, the protein has a half-life in vivo at least three fold higher than native human erythropoietin. The fusion protein also exhibits enhanced erythropoietic bioactivity in comparison to native human erythropoietin. In one embodiment, the fusion protein comprises the complete peptide sequence of a human erythropoietin (EPO) molecule and the peptide sequence of an Fc fragment of human immunoglobulin IgG1. The Fc fragment in the fusion protein includes the hinge region, CH2 and CH3 domains of human immunoglobulin IgG1. The EPO molecule may be linked directly to the Fc fragment to avoid extraneous peptide linkers and lessen the risk of an immunogenic response when administered in vivo. In one embodiment the hinge region is a human Fc fragment variant having a non-cysteine residue at amino acid 6. The invention also relates to nucleic acid and amino acid sequences encoding the fusion protein and transfected cell lines and methods for producing the fusion protein. The invention further includes pharmaceutical compositions comprising the fusion protein and methods of using the fusion protein and/or the pharmaceutical compositions, for example to stimulate erythropoiesis in subjects in need of therapy.

    Abstract translation: 描述了包含与免疫球蛋白肽部分连接的人促红细胞生成素肽部分的重组融合蛋白。 与天然存在的或重组的天然人促红细胞生成素相比，融合蛋白在体内具有延长的半衰期。 在本发明的一个实施方案中，蛋白质的体内半衰期比天然人促红细胞生成素高至少三倍。 与天然人促红细胞生成素相比，融合蛋白也表现出增强的红细胞生物活性。 在一个实施方案中，融合蛋白包含人促红细胞生成素（EPO）分子的完整肽序列和人免疫球蛋白IgG1的Fc片段的肽序列。 融合蛋白中的Fc片段包括人免疫球蛋白IgG1的铰链区，CH2和CH3结构域。 EPO分子可以直接连接到Fc片段，以避免外来的肽接头并且当在体内施用时减轻免疫原性应答的风险。 在一个实施方案中，铰链区是在氨基酸6具有非半胱氨酸残基的人Fc片段变体。本发明还涉及编码融合蛋白和转染细胞系的核酸和氨基酸序列以及用于产生融合蛋白的方法。 本发明还包括包含融合蛋白的药物组合物和使用融合蛋白和/或药物组合物的方法，例如刺激需要治疗的受试者的红细胞生成。

    Substituted heterocyclic compounds and methods of use
    35.
    发明申请
    Substituted heterocyclic compounds and methods of use 审中-公开
    取代的杂环化合物及其使用方法

    公开(公告)号：US20050288502A1

    公开(公告)日：2005-12-29

    申请号：US11166423

    申请日：2005-06-24

    Applicant: Denise Andersen ,  Michael Frohn ,  Fang-Tsao Hong ,  Longbin Liu ,  Patricia Lopez

    Inventor： Denise Andersen ,  Michael Frohn ,  Fang-Tsao Hong ,  Longbin Liu ,  Patricia Lopez

    IPC: A61K31/53 ,  C07D471/02 ,  C07D471/04 ,  C07D487/04

    CPC classification number: C07D471/04 ,  C07D487/04

    Abstract: The present invention relates to triazolopyrimidines, imidazolopyrimidines and derivatives thereof, and pharmaceutically acceptable salts thereof. Also included is a method of treatment of inflammation, rheumatoid arthritis, Pagets disease, osteoporosis, multiple myeloma, uveititis, acute or chronic myelogenous leukemia, pancreatic B cell destruction, osteoarthritis, rheumatoid spondylitis, gouty arthritis, inflammatory bowel disease, adult respiratory distress syndrome (ARDS), psoriasis, Crohn's disease, allergic rhinitis, ulcerative colitis, anaphylaxis, contact dermatitis, asthma, muscle degeneration, cachexia, Reiter's syndrome, type I diabetes, type II diabetes, bone resorption diseases, graft vs. host reaction, Alzheimer's disease, stroke, myocardial infarction, ischemia reperfusion injury, atherosclerosis, brain trauma, multiple sclerosis, cerebral malaria, sepsis, septic shock, toxic shock syndrome, fever, myalgias due to HIV-1, HIV-2, HIV-3, cytomegalovirus (CMV), influenza, adenovirus, the herpes viruses or herpes zoster infection in a mammal comprising administering an effective amount a compound as described above.

    Abstract translation: 本发明涉及三唑并嘧啶，咪唑并嘧啶及其衍生物及其药学上可接受的盐。 还包括治疗炎症，类风湿性关节炎，佩吉特病，骨质疏松症，多发性骨髓瘤，葡萄膜炎，急性或慢性骨髓性白血病，胰腺B细胞破坏，骨关节炎，类风湿性脊椎炎，痛风性关节炎，炎性肠病，成人呼吸窘迫综合征 （ARDS），牛皮癣，克罗恩病，过敏性鼻炎，溃疡性结肠炎，过敏反应，接触性皮炎，哮喘，肌肉变性，恶病质，赖特综合征，I型糖尿病，II型糖尿病，骨吸收疾病，移植物抗宿主反应，阿尔茨海默病 ，中风，心肌梗塞，缺血再灌注损伤，动脉粥样硬化，脑外伤，多发性硬化，脑疟疾，败血症，败血性休克，中毒性休克综合征，发热，HIV-1，HIV-2，HIV-3，巨细胞病毒 ），流感病毒，腺病毒，哺乳动物中的疱疹病毒或带状疱疹感染，包括给予有效量的如上所述的化合物。

    Substituted heterocyclic compounds and methods of use
    36.
    发明申请
    Substituted heterocyclic compounds and methods of use 失效
    取代的杂环化合物及其使用方法

    公开(公告)号：US20050187223A1

    公开(公告)日：2005-08-25

    申请号：US11041151

    申请日：2005-01-21

    Applicant: Michael Frohn ,  Fang-Tsao Hong ,  Longbin Liu ,  Patricia Lopez ,  Aaron Siegmund ,  Seifu Tadesse ,  Nuria Tamayo

    Inventor： Michael Frohn ,  Fang-Tsao Hong ,  Longbin Liu ,  Patricia Lopez ,  Aaron Siegmund ,  Seifu Tadesse ,  Nuria Tamayo

    IPC: A61K31/506 ,  A61K31/513 ,  A61K31/519 ,  C07D471/04 ,  C07D487/04

    CPC classification number: C07D487/04 ,  C07D471/04

    Abstract: The present invention relates to pyrimidinones and pyridones and derivatives thereof, and pharmaceutically acceptable salts thereof. Also included is a method of treatment of inflammation, rheumatoid arthritis, Pagets disease, osteoporosis, multiple myeloma, uveititis, acute or chronic myelogenous leukemia, pancreatic β cell destruction, osteoarthritis, rheumatoid spondylitis, gouty arthritis, inflammatory bowel disease, adult respiratory distress syndrome (ARDS), psoriasis, Crohn's disease, allergic rhinitis, ulcerative colitis, anaphylaxis, contact dermatitis, asthma, muscle degeneration, cachexia, Reiter's syndrome, type I diabetes, type II diabetes, bone resorption diseases, graft vs. host reaction, Alzheimer's disease, stroke, myocardial infarction, ischemia reperfusion injury, atherosclerosis, brain trauma, multiple sclerosis, cerebral malaria, sepsis, septic shock, toxic shock syndrome, fever, myalgias due to HIV-1, HIV-2, HIV-3, cytomegalovirus (CMV), influenza, adenovirus, the herpes viruses or herpes zoster infection in a mammal comprising administering an effective amount a compound as described above.

    Abstract translation: 本发明涉及嘧啶酮和吡啶酮及其衍生物及其药学上可接受的盐。 还包括治疗炎症，类风湿性关节炎，斑节病，骨质疏松症，多发性骨髓瘤，葡萄膜炎，急性或慢性骨髓性白血病，胰腺β细胞破坏，骨关节炎，类风湿性脊椎炎，痛风性关节炎，炎性肠病，成人呼吸窘迫综合征 （ARDS），牛皮癣，克罗恩病，过敏性鼻炎，溃疡性结肠炎，过敏反应，接触性皮炎，哮喘，肌肉变性，恶病质，赖特综合征，I型糖尿病，II型糖尿病，骨吸收疾病，移植物抗宿主反应，阿尔茨海默病 ，中风，心肌梗塞，缺血再灌注损伤，动脉粥样硬化，脑外伤，多发性硬化，脑疟疾，败血症，败血性休克，中毒性休克综合征，发热，HIV-1，HIV-2，HIV-3，巨细胞病毒 ），流感病毒，腺病毒，哺乳动物中的疱疹病毒或带状疱疹感染，包括给予有效量的如上所述的化合物。

    Substituted heterocyclic compounds and methods of use
    37.
    发明申请
    Substituted heterocyclic compounds and methods of use 失效

    公开(公告)号：US20050043301A1

    公开(公告)日：2005-02-24

    申请号：US10923067

    申请日：2004-08-20

    Applicant: Longbin Liu ,  Patricia Lopez ,  Manoj Bajpai ,  Aaron Siegmund

    Inventor： Longbin Liu ,  Patricia Lopez ,  Manoj Bajpai ,  Aaron Siegmund

    IPC: C07D401/04 ,  C07D487/04 ,  C07D417/02 ,  A61K31/513 ,  A61K31/5377 ,  A61K31/541 ,  C07D43/02

    CPC classification number: C07D487/04 ,  C07D401/04

    Abstract: The present invention relates to compounds having the general formula or a pharmaceutically acceptable salt thereof, wherein R1 is a saturated or unsaturated 5-, 6- or 7-membered, ring containing 0, 1, 2 or 3 atoms selected from N, O and S, wherein the ring may be fused with a benzo group, and is substituted by 0, 1 or 2 oxo groups, and wherein R1 is additionally substituted; and R2 is a substituted C1-6alkyl. Also included is a method of prophylaxis or treatment of inflammation, rheumatoid arthritis, Pagets disease, osteoporosis, multiple myeloma, uveititis, acute or chronic myelogenous leukemia, pancreatic β cell destruction, osteoarthritis, rheumatoid spondylitis, gouty arthritis, inflammatory bowel disease, adult respiratory distress syndrome (ARDS), psoriasis, Crohn's disease, allergic rhinitis, ulcerative colitis, anaphylaxis, contact dermatitis, asthma, muscle degeneration, cachexia, Reiter's syndrome, type I diabetes, type II diabetes, bone resorption diseases, graft vs. host reaction, Alzheimer's disease, stroke, myocardial infarction, ischemia reperfusion injury, atherosclerosis, brain trauma, multiple sclerosis, cerebral malaria, sepsis, septic shock, toxic shock syndrome, fever, myalgias due to HIV-1, HIV-2, HIV-3, cytomegalovirus (CMV), influenza, adenovirus, the herpes viruses or herpes zoster infection in a mammal comprising administering an effective amount a compound as described above.

    Substituted heterocyclic compounds and methods of use
    38.
    发明申请
    Substituted heterocyclic compounds and methods of use 失效
    取代的杂环化合物及其使用方法

    公开(公告)号：US20050020592A1

    公开(公告)日：2005-01-27

    申请号：US10897884

    申请日：2004-07-23

    Applicant: Celia Dominguez ,  Timothy Harvey ,  Longbin Liu ,  Aaron Siegmund

    Inventor： Celia Dominguez ,  Timothy Harvey ,  Longbin Liu ,  Aaron Siegmund

    IPC: A61P29/00 ,  C07D401/04 ,  C07D401/14 ,  C07D487/04 ,  A61K31/53 ,  A61K31/4965 ,  A61K31/5377 ,  C07

    CPC classification number: C07D401/14 ,  C07D401/04 ,  C07D487/04

    Abstract: The present invention relates to compounds having the general formula or a pharmaceutically acceptable salt thereof, wherein R1 is a saturated or unsaturated 5-, 6- or 7-membered, ring containing 0, 1, 2 or 3 atoms selected from N, 0 and S, wherein the ring may be fused with a benzo group, and is substituted by 0, 1 or 2 oxo groups, and wherein R1 is additionally substituted; and R2 is a substituted C1-6alkyl. Also included is a method of prophylaxis or treatment of inflammation, rheumatoid arthritis, Pagets disease, osteoporosis, multiple myeloma, uveititis, acute or chronic myelogenous leukemia, pancreatic β cell destruction, osteoarthritis, rheumatoid spondylitis, gouty arthritis, inflammatory bowel disease, adult respiratory distress syndrome (ARDS), psoriasis, Crohn's disease, allergic rhinitis, ulcerative colitis, anaphylaxis, contact dermatitis, asthma, muscle degeneration, cachexia, Reiter's syndrome, type I diabetes, type II diabetes, bone resorption diseases, graft vs. host reaction, Alzheimer's disease, stroke, myocardial infarction, ischemia reperfusion injury, atherosclerosis, brain trauma, multiple sclerosis, cerebral malaria, sepsis, septic shock, toxic shock syndrome, fever, myalgias due to HIV-1, HIV-2, HIV-3, cytomegalovirus (CMV), influenza, adenovirus, the herpes viruses or herpes zoster infection in a mammal comprising administering an effective amount a compound as described above.

    Abstract translation: 本发明涉及具有通式的化合物或其药学上可接受的盐，其中R 1是饱和或不饱和的含有0,1,2或3个选自N， ，0和S，其中所述环可以与苯并稠合，并且被0,1或2个氧代基取代，并且其中R 1另外被取代; R 2是取代的C 1-6烷基。 还包括预防或治疗炎症，类风湿性关节炎，斑节病，骨质疏松症，多发性骨髓瘤，葡萄膜炎，急性或慢性骨髓性白血病，胰腺β细胞破坏，骨关节炎，类风湿性脊椎炎，痛风性关节炎，炎性肠病，成人呼吸 窘迫综合征（ARDS），牛皮癣，克罗恩病，过敏性鼻炎，溃疡性结肠炎，过敏反应，接触性皮炎，哮喘，肌肉退化，恶病质，赖特综合征，I型糖尿病，II型糖尿病，骨吸收疾病，移植物抗宿主反应， 阿尔茨海默病，中风，心肌梗死，缺血再灌注损伤，动脉粥样硬化，脑外伤，多发性硬化，脑疟疾，败血症，败血性休克，中毒性休克综合征，发热，HIV-1，HIV-2，HIV-3，巨细胞病毒引起的肌痛 （CMV），流感，腺病毒，哺乳动物中的疱疹病毒或带状疱疹感染，包括给予有效量的化合物d 以上所述。

    Recombinant human interferon-like proteins
    40.
    发明授权
    Recombinant human interferon-like proteins 有权
    重组人干扰素样蛋白

    公开(公告)号：US08425895B2

    公开(公告)日：2013-04-23

    申请号：US12665682

    申请日：2007-06-22

    Applicant: Haitao Wang ,  Chunsheng Mao ,  Jizhi Li ,  Ling Wang ,  Yong Du ,  Longbin Liu ,  Jing Xu ,  Rui Zhang

    Inventor： Haitao Wang ,  Chunsheng Mao ,  Jizhi Li ,  Ling Wang ,  Yong Du ,  Longbin Liu ,  Jing Xu ,  Rui Zhang

    IPC: A61K38/21 ,  C07K14/00 ,  C08H1/02 ,  C12P21/04 ,  C07H21/04 ,  A61K38/00

    CPC classification number: C07K14/56 ,  A61K38/00 ,  C07K14/555

    Abstract: This application relates to recombinant human interferon-like proteins. In one embodiment a recombinant protein created by gene shuffling technology is described having enhanced anti-viral and anti-proliferative activities in comparison to naturally occurring human interferon alpha 2b (HuIFN-α2b). The invention encompasses a polynucleotide encoding the protein and recombinant vectors and host cells comprising the polynucleotide. Preferably the polynucleotide is selected from the group of polynucleotides each having a sequence at least 93% identical to SEQ ID: No. 1 and the protein is selected from the group of proteins each having an amino acid sequence at least 85% identical to SEQ ID NO: 2. The proteins and compositions comprising the proteins can be used for treatment of conditions responsive to interferon therapy, such as viral diseases and cancer.

    Abstract translation: 本申请涉及重组人类干扰素样蛋白。 在一个实施方案中，与天然存在的人干扰素α2b（HuIFN-α2b）相比，描述了通过基因改组技术产生的重组蛋白质具有增强的抗病毒和抗增殖活性。 本发明包括编码蛋白质的多核苷酸和包含多核苷酸的重组载体和宿主细胞。 优选地，多核苷酸选自各自具有与SEQ ID：No.1至少93％相同的序列的多核苷酸，并且所述蛋白质选自蛋白质组，其各自具有与SEQ ID NO：至少85％相同的氨基酸序列 包含蛋白质的蛋白质和组合物可用于治疗对干扰素治疗（例如病毒性疾病和癌症）有反应的病症。

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