WEI, Ge,SHEPARD, H. Michael,ZHAO, Qiping,CONNOR, Robert James
申请号：
ES12816624
公开号：
ES2609582T3
申请日:
2012.12.28
申请国别(地区):
ES
年份:
2017
代理人:
摘要：
A modified PH20 polypeptide, comprising an amino acid replacement in an unmodified PH20 polypeptide, wherein: the unmodified PH20 polypeptide consists of the amino acid sequence set forth in any of SEQ ID NO: 3, 7 or 32-66 ； Amino acid replacement is an amino acid position corresponding to a position 10, 12, 20, 22, 26, 34, 36, 46, 50, 52, 58, 68, 70, 74, 82, 83, 84, 86, 97 , 127, 138, 142, 143, 144, 166, 169, 174, 193, 195, 196, 204, 205, 206, 213, 10 234, 237, 238, 240, 249, 261, 267, 277, 279, 291, 309, 310, 314, 315, 317, 318, 347, 367, 375, 376, 399, 401, 407, 416, 419, 421, 431, 433, 439, 440, 443 or 445 in reference to positions of amino acids set forth in SEQ ID NO: 3, provided that if the modified PH20 polypeptide includes only a single amino acid replacement, the replacement does not correspond to amino acid replacements V12A or E249Q in reference to the positions to amino acids exposed in SEQ ID NO: 3, corresponding amino acid positions are identified by alignment of the PH20 polypeptide with the polypeptide set forth in SEQ ID NO: 3； the modified PH20 polypeptide shows increased stability in the presence of a phenolic preservative or preservatives compared to unmodified PH20 polypeptide that does not contain the amino acid replacement； Increased stability is manifested as increased hyaluronidase activity in the presence of the preservative or phenolic preservatives compared to the hyaluronidase activity of the unmodified PH20 polypeptide that does not contain the amino acid replacement in the presence of the same or the same phenolic preservatives, and the activity is compared With the same conditions.Un polipéptido de PH20 modificado, que comprende un reemplazo de aminoácido en un polipéptido de PH20 no modificado, donde: el polipéptido de PH20 no modificado consiste en la secuencia de aminoácidos expuesta en cualquiera de las SEQ ID NO: 3, 7 o 32-66； el reemplazo de aminoácidos es una posición de aminoácido correspondiente a una posición 10, 12, 20, 22
