公开(公告)号：US20120130052A1

公开(公告)日：2012-05-24

申请号：US13360220

申请日：2012-01-27

Applicant: George Anello CHIARELLO ,  Ayman SAHLI

Inventor： George Anello CHIARELLO ,  Ayman SAHLI

IPC: C07K1/107 ,  C07C323/48 ,  C07C319/06

CPC classification number: C07C319/20 ,  A61K47/6889 ,  C07C241/04 ,  C07C319/12 ,  C07C323/60

Abstract: A method is disclosed for preparing hydrazides from hydrazine and an acyl chloride which comprises the steps of (a) preparing a stirred substantially uniform slurry comprising hydrazine and an inert solvent at low temperature; and (b) adding an acyl chloride continuously to said slurry. The method avoids or limits production of undesired bis-hydrazide by-products. The method is used to prepare 3-methyl-3-mercaptobutanoic acid hydrazide, a molecule used to link calicheamicin to a monoclonal antibody.

Abstract translation: 公开了用于从肼和酰氯制备酰肼的方法，其包括以下步骤：（a）在低温下制备包含肼和惰性溶剂的搅拌的基本均匀的浆料; 和（b）向所述浆料中连续加入酰氯。 该方法避免或限制不需要的双酰肼副产物的生产。 该方法用于制备3-甲基-3-巯基丁酸酰肼，一种用于将加利车霉素与单克隆抗体连接的分子。

公开(公告)号：US08178097B2

公开(公告)日：2012-05-15

申请号：US12472237

申请日：2009-05-26

Applicant: Laird Bloom ,  Davinder Gill ,  Yulia Vugmeyster ,  Deborah A. Young ,  Margot O'Toole ,  Heath M. Guay ,  Karissa K. Adkins ,  Amy Arlene Weaver ,  Sadhana Jain ,  Maya Arai

Inventor： Laird Bloom ,  Davinder Gill ,  Yulia Vugmeyster ,  Deborah A. Young ,  Margot O'Toole ,  Heath M. Guay ,  Karissa K. Adkins ,  Amy Arlene Weaver ,  Sadhana Jain ,  Maya Arai

IPC: A61K39/395 ,  C07K16/28

CPC classification number: G01N33/6869 ,  A61K38/00 ,  A61K2039/505 ,  C07K16/2866 ,  C07K2317/21 ,  C07K2317/56 ,  C07K2317/565 ,  C07K2317/622 ,  C07K2317/73 ,  C07K2317/732 ,  C07K2317/76 ,  C07K2317/92 ,  C07K2319/30 ,  G01N2333/54

Abstract: The present invention provides binding proteins and antigen-binding fragments thereof, including human antibodies, that specifically bind to the human interleukin-21 receptor (IL-21R), and methods of using them. The binding proteins can act as, e.g., antagonists of IL-21R activity, thereby modulating immune responses in general, and those mediated by IL-21R in particular. The disclosed compositions and methods may be used, e.g., in diagnosing, treating, and/or preventing IL-21R-associated disorders, e.g., inflammatory disorders, autoimmune diseases, allergies, transplant rejection, and other immune system disorders.

Abstract translation: 本发明提供特异性结合人白细胞介素-21受体（IL-21R）的结合蛋白及其抗原结合片段，包括人抗体，以及使用它们的方法。 结合蛋白可以作为例如IL-21R活性的拮抗剂，从而调节一般的免疫应答，特别是由IL-21R介导的那些。 所公开的组合物和方法可以用于例如诊断，治疗和/或预防IL-21R相关疾病，例如炎性疾病，自身免疫疾病，过敏，移植排斥和其它免疫系统疾病。

公开(公告)号：US20120107928A1

公开(公告)日：2012-05-03

申请号：US13346042

申请日：2012-01-09

Applicant: Jane Aghajanian ,  William J. Dunham ,  Neil M. Wolfman ,  Denise O'Hara ,  Monique V. Davies ,  Geertruida M. Veldman ,  Kristie Grove Bridges ,  Lisa-Anne Whittemore ,  Tejvir S. Khurana ,  Mary L. Bouxsein

Inventor： Jane Aghajanian ,  William J. Dunham ,  Neil M. Wolfman ,  Denise O'Hara ,  Monique V. Davies ,  Geertruida M. Veldman ,  Kristie Grove Bridges ,  Lisa-Anne Whittemore ,  Tejvir S. Khurana ,  Mary L. Bouxsein

IPC: C12N15/13 ,  C12N5/16

CPC classification number: C07K16/22 ,  A01K2217/075 ,  A61K2039/505 ,  C07K14/475 ,  C07K2317/76

Abstract: The disclosure provides novel antibodies against growth and differentiation factor-8 (GDF-8), including antibody fragments, which inhibit GDF-8 activity in vitro and in vivo. The disclosure also provides methods for diagnosing, preventing, or treating degenerative disorders of muscle, bone, or insulin metabolism.

Abstract translation: 本公开提供了针对生长和分化因子-8（GDF-8）的新型抗体，其包括在体外和体内抑制GDF-8活性的抗体片段。 本公开还提供用于诊断，预防或治疗肌肉，骨骼或胰岛素代谢退行性疾病的方法。

公开(公告)号：US08158642B2

公开(公告)日：2012-04-17

申请号：US12579828

申请日：2009-10-15

Applicant: Christopher Michael Semko ,  Ying-zi Xu ,  Frank Stappenbeck ,  Jenifer Lea Smith ,  Kassandra Inez Rossiter ,  Juri Y. Fukuda ,  Andrei W. Konradi

Inventor： Christopher Michael Semko ,  Ying-zi Xu ,  Frank Stappenbeck ,  Jenifer Lea Smith ,  Kassandra Inez Rossiter ,  Juri Y. Fukuda ,  Andrei W. Konradi

IPC: A01N43/54 ,  A61K31/505 ,  C07D239/02

CPC classification number: C07D417/12 ,  C07D239/50 ,  C07D401/12 ,  C07D405/12 ,  C07D409/12 ,  C07D409/14

Abstract: Disclosed are compounds which bind VLA-4. Certain of these compounds also inhibit leukocyte adhesion and, in particular, leukocyte adhesion mediated by VLA-4. Such compounds are useful in the treatment of inflammatory diseases in a mammalian patient, e.g., human, such as asthma, Alzheimer's disease, atherosclerosis, AIDS dementia, diabetes, inflammatory bowel disease, rheumatoid arthritis, tissue transplantation, tumor metastasis and myocardial ischemia. The compounds can also be administered for the treatment of inflammatory brain diseases such as multiple sclerosis.

Abstract translation: 公开了结合VLA-4的化合物。 这些化合物中的某些也抑制白细胞粘附，特别是由VLA-4介导的白细胞粘附。 这样的化合物可用于治疗哺乳动物患者，例如人类例如哮喘，阿尔茨海默氏病，动脉粥样硬化，艾滋病痴呆，糖尿病，炎性肠病，类风湿性关节炎，组织移植，肿瘤转移和心肌缺血等炎性疾病。 化合物也可以用于治疗炎性脑疾病如多发性硬化症。

公开(公告)号：US08143385B2

公开(公告)日：2012-03-27

申请号：US12353812

申请日：2009-01-14

Applicant: Viia Valge-Archer ,  Andrew James Williams ,  Deborah A. Young ,  Matthew J. Whitters ,  Mary Collins ,  Joann Witek

Inventor： Viia Valge-Archer ,  Andrew James Williams ,  Deborah A. Young ,  Matthew J. Whitters ,  Mary Collins ,  Joann Witek

IPC: C07H21/04 ,  A61K39/00 ,  C12N5/16 ,  H01N33/53

CPC classification number: C07K16/2866 ,  A61K2039/505 ,  C07K2317/56 ,  C07K2317/622

Abstract: The present application provides human antibodies and antigen binding fragments thereof that specifically bind to the human interleukin-21 receptor (IL-21R). The antibodies can act as antagonists of IL-21R activity, thereby modulating immune responses in general, and those mediated by IL-21R in particular. The disclosed compositions and methods may be used for example, in diagnosing, treating or preventing inflammatory disorders, autoimmune diseases, allergies, transplant rejection, cancer, and other immune system disorders.

Abstract translation: 本申请提供了特异性结合人白细胞介素-21受体（IL-21R）的人抗体及其抗原结合片段。 抗体可以作为IL-21R活性的拮抗剂，从而调节一般的免疫应答，特别是由IL-21R介导的那些。 所公开的组合物和方法可用于例如诊断，治疗或预防炎性疾病，自身免疫疾病，过敏，移植排斥，癌症和其他免疫系统疾病。

公开(公告)号：US08129524B2

公开(公告)日：2012-03-06

申请号：US13179730

申请日：2011-07-11

Applicant: Bogdan Kazimierz Wilk

Inventor： Bogdan Kazimierz Wilk

IPC: C07D265/12 ,  C07D207/30

CPC classification number: C07D413/04 ,  C07D207/34

Abstract: Methods for preparing cyclic carbamates and thiocarbamates containing cyanopyrrole moieties and of the formula are provided: Z are the same or different and are H, optionally substituted C1 to C6 alkyl, or CORA; RA is H, optionally substituted C1 to C6 alkyl, optionally substituted C1 to C6 alkoxy, or optionally substituted C1 to C6 aminoalkyl; Q are the same or different and are H, OH, NH2, CN, halogen, optionally substituted C1 to C6 alkyl, optionally substituted C2 to C6 alkenyl, optionally substituted C1 to C6 alkynyl, optionally substituted C1 to C6 alkoxy, optionally substituted C1 to C6 aminoalkyl, or CORB; and RB is H, optionally substituted C1 to C6 alkyl, optionally substituted C1 to C6 alkoxy, or optionally substituted C1 to C6 aminoalkyl. Compounds including 2-amino-5-(5-cyano-1-methyl-1H-pyrrol-2-yl) benzoicacid methyl ester, 5-[4-amino-3-(1-hydroxy-1-methyl-ethyl)-phenyl]-1-methyl-1H-pyrrole-2-carbonitrile, and 2-amino-5-(5-cyano-1-methyl-1H-pyrrol-2-yl)-phenyl-ethanone, or pharmaceutically acceptable salts thereof, and the uses thereof are also provided.

Abstract translation: 提供了含有氰基吡咯部分和下式的环状氨基甲酸酯和硫代氨基甲酸酯的方法：Z相同或不同，为H，任选取代的C 1 -C 6烷基或CORA; RA为H，任选取代的C 1至C 6烷基，任选取代的C 1至C 6烷氧基，或任选取代的C 1至C 6氨基烷基; Q相同或不同，为H，OH，NH 2，CN，卤素，任选取代的C 1至C 6烷基，任选取代的C 2至C 6烯基，任选取代的C 1至C 6炔基，任选取代的C 1至C 6烷氧基，任选取代的C 1至 C6氨基烷基或CORB; 且R B为H，任选取代的C 1至C 6烷基，任选取代的C 1至C 6烷氧基或任选取代的C 1至C 6氨基烷基。 包括2-氨基-5-（5-氰基-1-甲基-1H-吡咯-2-基）苯甲酸甲酯，5- [4-氨基-3-（1-羟基-1-甲基 - 乙基） - 苯基] -1-甲基-1H-吡咯-2-甲腈和2-氨基-5-（5-氰基-1-甲基-1H-吡咯-2-基） - 苯基 - 乙酮或其药学上可接受的盐， 并提供其用途。

公开(公告)号：US08129371B2

公开(公告)日：2012-03-06

申请号：US12251712

申请日：2008-10-15

Applicant: Arie Zask ,  Joshua Aaron Kaplan ,  Jeroen Cunera Verheijen ,  Kevin J. Curran ,  David James Richard ,  Semiramis Ayral-Kaloustian

Inventor： Arie Zask ,  Joshua Aaron Kaplan ,  Jeroen Cunera Verheijen ,  Kevin J. Curran ,  David James Richard ,  Semiramis Ayral-Kaloustian

IPC: C07D265/36 ,  C07D265/28 ,  A61K31/537 ,  A61P37/06 ,  A61P35/00 ,  C07D487/04 ,  C07D495/04

CPC classification number: C07D519/00

Abstract: The invention relates to thienopyrimidine and pyrazolopyrimidine compounds of the Formulas (Ia) and (IIa), or a pharmaceutically acceptable salt thereof, wherein the constituent variables are as defined herein compositions comprising the compounds, and methods for making and using the compounds.

Abstract translation: 本发明涉及式（Ia）和（IIa）的噻吩并嘧啶和吡唑并嘧啶化合物或其药学上可接受的盐，其中组成变量如本文所定义，包含该化合物的组合物，以及制备和使用该化合物的方法。

公开(公告)号：US08129145B2

公开(公告)日：2012-03-06

申请号：US11827301

申请日：2007-07-11

Applicant: Daniel R. Lasko ,  Stephan M. Koza

Inventor： Daniel R. Lasko ,  Stephan M. Koza

IPC: C12P21/04 ,  C07K14/00 ,  C12N5/06

CPC classification number: C12N5/0018 ,  C07K16/18 ,  C07K2317/41 ,  C12N5/0037 ,  C12N2500/20 ,  C12N2510/02

Abstract: An improved system for large scale production of glycoproteins in cell culture is provided. In accordance with the present invention, cells expressing a glycoprotein are grown in media that contain manganese at a concentration of between approximately 10 and 600 nM. The use of such a system allows production of a glycoprotein with an increased glycosylation pattern and/or a glycosylation pattern that more accurately reflects the glycosylation pattern of the naturally occurring glycoprotein. A glycoprotein expressed in accordance with the present invention may be advantageously used in the preparation of pharmaceutical compositions.

Abstract translation: 提供了一种用于细胞培养中大规模生产糖蛋白的改进体系。 根据本发明，表达糖蛋白的细胞在含有约10至600nM浓度的锰的培养基中生长。 使用这种系统允许生产具有更准确地反映天然存在的糖蛋白的糖基化模式的增加的糖基化模式和/或糖基化模式的糖蛋白。 根据本发明表达的糖蛋白可有利地用于制备药物组合物。

公开(公告)号：US20120046227A1

公开(公告)日：2012-02-23

申请号：US13211755

申请日：2011-08-17

Applicant: Stephen Berasi ,  Robert Vincent Martinez ,  Michael John Cain ,  John Wozney ,  Howard Seeherman ,  Z. Sean Juo ,  Valerie Calabro ,  Christopher Todd Brown

Inventor： Stephen Berasi ,  Robert Vincent Martinez ,  Michael John Cain ,  John Wozney ,  Howard Seeherman ,  Z. Sean Juo ,  Valerie Calabro ,  Christopher Todd Brown

IPC: A61K38/18 ,  C07H21/04 ,  A61P19/04 ,  C12N5/077 ,  A61P19/08 ,  C07K14/51 ,  C12P21/02

CPC classification number: C07K14/51 ,  A61K38/00

Abstract: The invention relates to novel designer osteogenic proteins having altered affinity for a cognate receptor, nucleic acids encoding the same, and methods of use therefor. More preferably, the novel designer osteogenic proteins are designer BMPs and have altered affinity for a cognate BMP receptor. The designer BMPs demonstrate altered biological characteristics and provide potential useful novel therapeutics.

Abstract translation: 本发明涉及对同型受体具有改变的亲和力的新型设计者成骨蛋白质，及其编码的核酸及其使用方法。 更优选地，新设计的成骨蛋白是设计者BMP并且对同源BMP受体具有改变的亲和力。 设计者BMPs展示了改变的生物学特征，并提供潜在的有用的新型治疗。

公开(公告)号：US08114869B2

公开(公告)日：2012-02-14

申请号：US13106494

申请日：2011-05-12

Applicant: Marc Sadler Tesconi ,  Mannching Sherry Ku ,  Yan Xu

Inventor： Marc Sadler Tesconi ,  Mannching Sherry Ku ,  Yan Xu

IPC: A61K31/536 ,  A61P15/18 ,  C07D265/18

CPC classification number: C07D413/04 ,  C07D265/18 ,  C07B2200/13

Abstract: Tanaproget polymorph Form II, processes for preparing tanaproget polymorph Form II, pharmaceutical compositions including tanaproget polymorph Form II, micronized tanaproget polymorph Form II, and processes for converting Form II to tanaproget Form I are provided. Also provided are methods of contraception, hormone replacement therapy, stimulation of food intake and treating or preventing uterine myometrial fibroids, benign prostatic hypertrophy, benign and malignant neoplastic disease, dysfunctional bleeding, uterine leiomyomata, endometriosis, polycystic ovary syndrome, or carcinomas and adenocarcinomas comprising administering polymorph Form II to a mammalian subject.

Abstract translation: Tanaproget多晶型物II，制备tanaproget多晶型II的方法，包括tanaproget多晶型II，微粉化tanaproget多晶型II的药物组合物，以及将II型转化成tanaproget形式I的方法。 还提供了避孕，激素替代疗法，刺激食物摄取和治疗或预防子宫肌层肌瘤，良性前列腺肥大，良性和恶性肿瘤性疾病，功能障碍性出血，子宫平滑肌瘤，子宫内膜异位症，多囊卵巢综合征或癌和腺癌的方法，包括 向哺乳动物受试者施用多晶型II。