[发明专利]修饰的显示增加的蛋白酶抗性的促红细胞生成素(EPO)多肽及其药物组合物

权利要求书

1.一种修饰的促红细胞生成素(EPO)多肽，其包含：

在被不同糖基化位点掩蔽的掩蔽is-Hit残基处的2个氨基酸修饰；和

在非掩蔽is-Hit残基处的一或多个额外的氨基酸修饰，条件是所述修饰不是选自R4H/K20Q/R139H/L80I；E159N/K20Q/R139H/L93I；L153V/K20Q/R139H/L80I；和E159N/K20Q/R139H/L80I。

2.权利要求1的修饰的EPO多肽，其中所述修饰选自K20Q/R139H/R4H；K20Q/R139H/K52N；K20Q/R139H/E159N；L80I/R139H/R4H；L80I/R139H/E159N；L80I/R139H/K52N；L80I/R139H/L153V；L93V/R139H/R4H；L93V/R139H/E159N；L93V/R139H/K52N；L93V/R139H/L153V；R4H/K20Q/L93I/R139H；K20Q/L93I/R139H/K52N；K20Q/L93I/R139H/L153V；K20Q/K52N/L80I/R139H；K20Q/L93V/R139H/R4H；K20Q/L93V/R139H/E159N；K20Q/L93V/R139H/K52N；K20Q/L93V/R139H/L153V；L93I/R139H/E159N；L93I/R139H/K52N；L93I/R139H/L153V；L93I/R139H/R4H；K20Q/L80I/R139H/E159N/R4H；K20Q/L80I/R139H/E159N/K52N；K20Q/L80I/R139H/L153V/E159N；K20Q/L80I/R139H/E159N/L93I；K20Q/L80I/R139H/L153V/R4H；K20Q/K52N/L80I/R139H/L153V；K20Q/L80I/R139H/L153V/L93I；K20Q/R139H/E159N/R4H；K20Q/R139H/E159N；K20Q/R139H/E159N/L153V；K20Q/L93I/R139H/E159N/R4H；K20Q/L93I/R139H/E159N/K52N；K20Q/L93I/R139H/E159N/L153V；R4H/K20Q/K52N/L80I/R139H；R4H/K20Q/L80I/R139H/L93I；K20Q/R139H/L153V/R4H；K20Q/R139H/K52N/L153V；R4H/K20Q/L93I/R139H/K52N；R4H/K20Q/L93I/R139H/L153V；K20Q/L93V/R139H/E159N/R4H；K20Q/L93V/R139H/E159N/K52N；和K20Q/R139H/R4H/K52N。

3.权利要求1或2的修饰的EPO多肽，其中所述修饰选自K20Q/L80I/R139H/E159N；K20Q/L80I/R139H/E159N/R4H；K20Q/L80I/R139H/E159N/K52N；K20Q/L80I/R139H/L153V/R4H；K20Q/R139H/E159N/K52N；K20Q/R139H/E159N/L153V；K20Q/L93I/R139H/E159N/R4H；K20Q/L93I/R139H/E159N/K52N；K20Q/L93I/R139H/E159N/L153V；和K20Q/L93V/R139H/E159N/K52N。

4.一种修饰的促红细胞生成素(EPO)多肽，其在未修饰的EPO多肽中包含选自L80I/R139H/L93I；K20Q/L80I/R139H/L93I；K20Q/L93I；K20Q/L153V；K20Q/E159N；K20Q/R4H；K20Q/K52N；K20Q/L80I；和K20Q/L93V的2或多个氨基酸修饰。

5.权利要求1-4任一项的修饰的EPO多肽，其中所述多肽是糖基化的、部分糖基化的或去糖基化的。

6.权利要求5的修饰的EPO多肽，其中所述多肽由于在糖基化位点N24、N38或N83的一或多个处的一或多个进一步的氨基修饰而是部分糖基化的或去糖基化的，其中所述修饰消除了该位点的糖基化。

7.权利要求6的修饰的EPO多肽，其中所述修饰是选自N24H，N38H，N83H，N24K，N38K和N83K的氨基酸置换。