公开(公告)号：US20070219116A1

公开(公告)日：2007-09-20

申请号：US10593466

申请日：2005-03-18

Applicant: Mariusz Szkudlinski ,  Bruce Weintraub

Inventor： Mariusz Szkudlinski ,  Bruce Weintraub

IPC: A61K38/24 ,  C07H21/04 ,  C07K14/59 ,  C12N15/63 ,  C12N5/06 ,  C12N5/08

CPC classification number: A61K38/24 ,  C07K14/59 ,  A61K2300/00

Abstract: This invention provides superactive analogs of FSH demonstrating enhanced bioactivity both in vitro and in vivo as compared to wild type FSH. In particular, the analogs of the invention demonstrate at least a ten fold increase in potency or at least a ten percent increase in maximal efficacy as compared to wild type protein. The analogs are particularly useful for treating subjects showing low FSH receptor expression or poor FSH receptor responsiveness, and for the treatment of any condition associated with glycoprotein hormone activity.

Abstract translation: 与野生型FSH相比，本发明提供FSH的超活性类似物，其表现出体外和体内增强的生物活性。 特别地，与野生型蛋白质相比，本发明的类似物表现出至少十倍的效力增加或最大功效的至少百分之十的增加。 类似物对于治疗显示低FSH受体表达或不良FSH受体反应性的受试者以及用于治疗与糖蛋白激素活性相关的任何病症特别有用。

公开(公告)号：US20060183672A1

公开(公告)日：2006-08-17

申请号：US11409428

申请日：2006-04-21

Applicant: Mariusz Szkudlinski ,  Bruce Weintraub ,  Mathis Grossmann

Inventor： Mariusz Szkudlinski ,  Bruce Weintraub ,  Mathis Grossmann

IPC: C07K14/575 ,  C07H21/04 ,  A61K38/22

CPC classification number: C07K14/59 ,  A61K38/00 ,  Y10S530/85

Abstract: The invention is directed toward a human glycoprotein hormone having at least one, two, three, four, or five basic amino acids in the α-subunit at positions selected from the group consisting of positions 11, 13, 14, 16, 17, and 20. The invention is also directed to a human glycoprotein where at least one of the amino acids at position 58, 63, and 69 of the β-subunit of the human thyroid stimulating hormone are basic amino acids. The invention is further directed to a modified human glycoprotein hormone having increased activity over a wild-type human glycoprotein hormone, where the modified human glycoprotein comprises a basic amino acid substituted at a position corresponding to the same amino acid position in a non-human glycoprotein hormone having an increased activity over the wild-type human glycoprotein hormone. The invention is also directed to a method of constructing superactive nonchimeric analogs of human hormones comprising comparing the amino acid sequence of a more active homolog from another species to the human hormone, and selecting superactive analogs from the substituted human hormones. The invention is also directed to nucleic acids encoding the modified human glycoprotein hormones, vectors containing those nucleic acids, and host cells containing those vectors.

Abstract translation: 本发明涉及在α亚基中具有至少一个，二个，三个，四个或五个碱性氨基酸的人类糖蛋白激素，所述碱基氨基酸位于选自下组的位置：第11,13,14,16,17和 本发明还涉及人类糖蛋白，其中人类甲状腺刺激激素的β-亚基的58,63和69位的至少一个氨基酸是碱性氨基酸。 本发明进一步涉及一种与野生型人类糖蛋白激素相比具有增加的活性的修饰的人类糖蛋白激素，其中修饰的人类糖蛋白包含在非人类糖蛋白中与相同氨基酸位置相应位置取代的碱性氨基酸 具有比野生型人类糖蛋白激素增加的活性的激素。 本发明还涉及一种构建人类激素的超活性非嵌段类似物的方法，其包括将来自另一物种的更有活性同源物的氨基酸序列与人激素进行比较，以及从所述取代的人类激素中选择超活性类似物。 本发明还涉及编码修饰的人类糖蛋白激素的核酸，含有这些核酸的载体和含有这些载体的宿主细胞。