WU, LAURENCE I.,吴逸之,吳逸之,WU, BRYAN T.H.,吴灿辉,吳燦輝,KAO, KUO HIS,高国席,高國席,SHEN, LIMING,沈立明,TENG, KELLY,邓克立,鄧克立
申请号：
TW095150007
公开号：
TWI381850B
申请日:
2006.12.29
申请国别(地区):
TW
年份:
2013
代理人:
摘要：
This invention relates to a polypeptide-polymer conjugate that includes a polypeptide moiety, a polyalkylene oxide moiety, a linker connecting the polypeptide moiety with the polyalkylene oxide moiety, a first linkage between the polypeptide moiety and the linker, and a second linkage between the polyalkylene oxide moiety and the linker. The polypeptide moiety can contain a human interferon-α moiety and 1-6 additional amino acid residues at the N-terminus of the human interferon-α moiety. The polyalkylene oxide moiety can contain 1-20,000 C1-C8alkylene oxide repeating units. The linker can be C1-C8alkylene, C1-C8heteroalkylene, C3-C8cycloalkylene, C3-C8heterocycloalkylene, arylene, heteroarylene, aralkylene, or -Ar-X-(CH2)n-, in which Ar can be arylene or heteroarylene, X can be O, S, or N(R), R being H or C1-C10alkyl, and n can be 1-10. Each of the first and second linkages, independently, can be a carboxylic ester, carbonyl, carbonate, amide, carbamate, urea, ether, thio, sulfonyl, sulfinyl, amino, imino, hydroxyamino, phosphonate, or phosphate group.本發關於藥物與聚合物之共軛物，其包括多肽部分、聚環氧烷部分、連結多肽部分與聚環氧烷部分的連接物、在多肽部分與連接物之間的第一鏈結、以及在聚環氧烷部分與連接物之間的第二鏈結。多肽部分可含有人類α干擾素部分與位在人類α干擾素部分之氮端的1至6個額外胺基酸殘基。聚環氧烷部分可含有1至20,000個C1－C8環氧烷重複單元。連接物可為C1－C8伸烷基、C1－C8雜伸烷基、C3－C8環伸烷基、C3－C8雜伸烷基、伸苯基、雜伸苯基、芳基伸烷基、或－Ar－X－(CH2)n－，其中Ar可為伸芳基或雜伸芳基，X可為O、S或N(R)，R為氫或C1－C10烷基及n可為1至10。第一與第二鏈結每一者獨立地可為羧酸酯、羰基、碳酸鹽、醯胺基、胺基甲酸基、尿素、醚、硫基、磺醯基、亞磺醯基、胺基、亞胺基、羥胺基、膦酸鹽或磷酸鹽。
