公开(公告)号：US20050043301A1

公开(公告)日：2005-02-24

申请号：US10923067

申请日：2004-08-20

申请人： Longbin Liu ,  Patricia Lopez ,  Manoj Bajpai ,  Aaron Siegmund

发明人： Longbin Liu ,  Patricia Lopez ,  Manoj Bajpai ,  Aaron Siegmund

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

CPC分类号： C07D487/04 ,  C07D401/04

摘要： 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.

公开(公告)号：US20050020592A1

公开(公告)日：2005-01-27

申请号：US10897884

申请日：2004-07-23

申请人： Celia Dominguez ,  Timothy Harvey ,  Longbin Liu ,  Aaron Siegmund

发明人： Celia Dominguez ,  Timothy Harvey ,  Longbin Liu ,  Aaron Siegmund

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

CPC分类号： C07D401/14 ,  C07D401/04 ,  C07D487/04

摘要： 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.

摘要翻译： 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。

公开(公告)号：US10117949B2

公开(公告)日：2018-11-06

申请号：US12162320

申请日：2007-01-25

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

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

IPC分类号： C07K14/505 ,  A61K38/18 ,  A61K39/00 ,  A61K47/48 ,  A61K38/00

摘要： 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.

公开(公告)号：US08067548B2

公开(公告)日：2011-11-29

申请号：US12180455

申请日：2008-07-25

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

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

IPC分类号： C12P21/08 ,  A61K39/00

CPC分类号： C12N15/62 ,  A61K47/6811 ,  A61K47/6835 ,  C07K2317/53 ,  C07K2319/30

摘要： A fusion protein having a non-immunoglobulin polypeptide having a cysteine residue proximal to the C terminal thereof, and an immunoglobulin component with a mutated hinge region is provided. The mutation comprises a point mutated site corresponding in position to the position in a native hinge region of the cysteine residue located nearest the cysteine residue of the non-Ig component. The distance from the cysteine residue of the non-immunoglobulin polypeptide and any remaining cysteine residues of the mutated hinge region is sufficient to prevent the formation of a disulphide bond therebetween.

摘要翻译： 提供了具有非免疫球蛋白多肽的融合蛋白，其具有接近其C末端的半胱氨酸残基和具有突变的铰链区的免疫球蛋白组分。 该突变包括位于位于最接近非Ig组分的半胱氨酸残基的半胱氨酸残基的天然铰链区的位置的点突变位点。 与非免疫球蛋白多肽的半胱氨酸残基和突变的铰链区的任何剩余半胱氨酸残基的距离足以防止其间形成二硫键。

公开(公告)号：US20100303759A1

公开(公告)日：2010-12-02

申请号：US12665682

申请日：2007-06-22

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

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

IPC分类号： A61K38/21 ,  C07H21/04 ,  C12N15/63 ,  C12N5/10 ,  C07K14/555 ,  A61P35/04 ,  A61P31/12

CPC分类号： C07K14/56 ,  A61K38/00 ,  C07K14/555

摘要： 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.

公开(公告)号：US20090297522A1

公开(公告)日：2009-12-03

申请号：US12162320

申请日：2007-01-27

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

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

IPC分类号： A61K39/395 ,  C07K16/18 ,  C12N15/11 ,  C12N15/00 ,  C12N5/06 ,  C12P21/02

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

摘要： 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.

摘要翻译： 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。

公开(公告)号：US06849639B2

公开(公告)日：2005-02-01

申请号：US09732546

申请日：2000-12-08

申请人： Celia Dominguez ,  Guoqing Chen ,  Ning Xi ,  Shimin Xu ,  Nianhe Han ,  Qingyian Liu ,  Qi Huang ,  Aaron Siegmund ,  Michael Handley ,  Longbin Liu ,  Alexander Kiselyov

发明人： Celia Dominguez ,  Guoqing Chen ,  Ning Xi ,  Shimin Xu ,  Nianhe Han ,  Qingyian Liu ,  Qi Huang ,  Aaron Siegmund ,  Michael Handley ,  Longbin Liu ,  Alexander Kiselyov

IPC分类号： C07D401/06 ,  A61K31/402 ,  A61K31/4025 ,  A61K31/4178 ,  A61K31/4355 ,  A61K31/438 ,  A61K31/4406 ,  A61K31/4709 ,  A61K31/496 ,  A61K31/506 ,  A61P3/10 ,  A61P9/00 ,  A61P9/10 ,  A61P17/02 ,  A61P19/00 ,  A61P27/02 ,  A61P29/00 ,  A61P35/00 ,  A61P35/04 ,  C07D207/26 ,  C07D207/277 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D405/12 ,  C07D405/14 ,  C07D409/12 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14 ,  C07D471/10

CPC分类号： C07D207/277 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D405/12 ,  C07D405/14 ,  C07D409/12 ,  C07D409/14 ,  C07D417/14

摘要： The invention comprises novel compounds that are effective in the prophylaxis and treatment of diseases, such as integrin receptors mediated diseases, in particular, diseases or conditions mediated by integrin receptors, such as a αvβ3, αvβ5, αvβ6, α5β1 and the like. The invention encompasses novel compounds, pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of such diseases and disorders. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

摘要翻译： 本发明包括有效预防和治疗诸如整联蛋白受体介导的疾病，特别是整联蛋白受体介导的疾病或病症的新型化合物，例如阿尔法派3，阿尔法派5，阿尔法博特6，α5β1等。 本发明包括新型化合物，其药学上可接受的盐，用于预防和治疗这些疾病和病症的药物组合物和方法。 本发明还涉及制备这些化合物的方法以及在这些方法中有用的中间体。