873959 CEREZYME injection IF20084
MR MR Drug Safety Update IF
I. 1 3 2 3 II. 1 4 2 4 3 4 4 4 5 5 6 5 7CAS 5 III. 1 6 2 6 3 6 4 7 5 7 IV. 1 8 2 8 3 8 4 8 5 9 6 9 7 () 9 8 9 9 9 10 9 11 10 12 10 13 10 14 10 15 10 V. 1 11 2 11 3 12 VI. 1 14 2 14 VII. 1 17 2 17 3 18 4 18 5 18 6 18 7 18 VIII. 1 19 2 19 3 19 4 19 5 19 1
6 20 7 20 8 21 9 22 10 22 11 23 12 23 13 23 14 23 15 24 16 24 IX. 1 25 2 25 X. 1 26 2 26 3 26 4 26 5 26 6 26 7 26 8 26 9 27 10 27 11 27 12 27 13 27 14 27 15 27 XI. 1 28 2 28 XII. 1 28 XIII. 1 28 2
I. Genzyme CorporationGenzyme 19945 82 4 103 Arg IIII 3
II. Ala-Arg-Pro-Cys-Ile-Pro-Lys-Ser-Phe-Gly-Tyr-Ser-Ser-Val-Val-Cys-Val-Cys-Asn-Ala- Thr-Tyr-Cys-Asp-Ser-Phe-Asp-Pro-Pro-Thr-Phe-Pro-Ala-Leu-Gly-Thr-Phe-Ser-Arg-Tyr- Glu-Ser-Thr-Arg-Ser-Gly-Arg-Arg-Met-Glu-Leu-Ser-Met-Gly-Pro-Ile-Gln-Ala-Asn-His- Thr-Gly-Thr-Gly-Leu-Leu-Leu-Thr-Leu-Gln-Pro-Glu-Gln-Lys-Phe-Gln-Lys-Val-Lys-Gly- Phe-Gly-Gly-Ala-Met-Thr-Asp-Ala-Ala-Ala-Leu-Asn-Ile-Leu-Ala-Leu-Ser-Pro-Pro-Ala- Gln-Asn-Leu-Leu-Leu-Lys-Ser-Tyr-Phe-Ser-Glu-Glu-Gly-Ile-Gly-Tyr-Asn-Ile-Ile-Arg- Val-Pro-Met-Ala-Ser-Cys-Asp-Phe-Ser-Ile-Arg-Thr-Tyr-Thr-Tyr-Ala-Asp-Thr-Pro-Asp- Asp-Phe-Gln-Leu-His-Asn-Phe-Ser-Leu-Pro-Glu-Glu-Asp-Thr-Lys-Leu-Lys-Ile-Pro-Leu- Ile-His-Arg-Ala-Leu-Gln-Leu-Ala-Gln-Arg-Pro-Val-Ser-Leu-Leu-Ala-Ser-Pro-Trp-Thr- Ser-Pro-Thr-Trp-Leu-Lys-Thr-Asn-Gly-Ala-Val-Asn-Gly-Lys-Gly-Ser-Leu-Lys-Gly-Gln- Pro-Gly-Asp-Ile-Tyr-His-Gln-Thr-Trp-Ala-Arg-Tyr-Phe-Val-Lys-Phe-Leu-Asp-Ala-Tyr- Ala-Glu-His-Lys-Leu-Gln-Phe-Trp-Ala-Val-Thr-Ala-Glu-Asn-Glu-Pro-Ser-Ala-Gly-Leu- Leu-Ser-Gly-Tyr-Pro-Phe-Gln-Cys-Leu-Gly-Phe-Thr-Pro-Glu-His-Gln-Arg-Asp-Phe-Ile- Ala-Arg-Asp-Leu-Gly-Pro-Thr-Leu-Ala-Asn-Ser-Thr-His-His-Asn-Val-Arg-Leu-Leu-Met- Leu-Asp-Asp-Gln-Arg-Leu-Leu-Leu-Pro-His-Trp-Ala-Lys-Val-Val-Leu-Thr-Asp-Pro-Glu- Ala-Ala-Lys-Tyr-Val-His-Gly-Ile-Ala-Val-His-Trp-Tyr-Leu-Asp-Phe-Leu-Ala-Pro-Ala- Lys-Ala-Thr-Leu-Gly-Glu-Thr-His-Arg-Leu-Phe-Pro-Asn-Thr-Met-Leu-Phe-Ala-Ser-Glu- Ala-Cys-Val-Gly-Ser-Lys-Phe-Trp-Glu-Gln-Ser-Val-Arg-Leu-Gly-Ser-Trp-Asp-Arg-Gly- Met-Gln-Tyr-Ser-His-Ser-Ile-Ile-Thr-Asn-Leu-Leu-Tyr-His-Val-Val-Gly-Trp-Thr-Asp- Trp-Asn-Leu-Ala-Leu-Asn-Pro-Glu-Gly-Gly-Pro-Asn-Trp-Val-Arg-Asn-Phe-Val-Asp-Ser- Pro-Ile-Ile-Val-Asp-Ile-Thr-Lys-Asp-Thr-Phe-Tyr-Lys-Gln-Pro-Met-Phe-Tyr-His-Leu-Gly- His-Phe-Ser-Lys-Phe-Ile-Pro-Glu-Gly-Ser-Gln-Arg-Val-Gly-Leu-Val-Ala-Ser-Gln-Lys- Asn-Asp-Leu-Asp-Ala-Val-Ala-Leu-Met-His-Pro-Asp-Gly-Ser-Ala-Val-Val-Val-Val-Leu- Asn-Arg-Ser-Ser-Lys-Asp-Val-Pro-Leu-Thr-Ile-Lys-Asp-Pro-Ala-Val-Gly-Phe-Leu-Glu- Thr-Ile-Ser-Pro-Gly-Tyr-Ser-Ile-His-Thr-Tyr-Leu-Trp-His-Arg-Gln 4
glycoprotein (molecular weight : ca. 60,000) consisting of 497 amino acid residues (C2532H3843N671O711S16 ; 55,509) prepared from - glucocerebrosidase, which was produced in Chinese hamster ovary cells by expression of a human cdna derived from the fetal human lung fibroblast cell line, by modification of sugar chains to expose mannose using enzyme treatment with sialidase, -galactosidase and hexosaminidase 5
III. ph µ 28 123 4 180mL250mL ph 5 6
7
IV. 8
28 369 12(14) 1 15(16) 1 18 2 ph RP-HPLC, SDS-PAGE ph 2327 3 137 2 RP-HPLC, SDS-PAGE 2 8 2832 248 12 1 5.1mL ph 2 8 2025 248 1224 250mL 200mL50mL 15.1mL 5mL 9
10
V. 11
12
13
VI. 14
µ µ 15
16
VII. 3.610.4 5.92.4 9.820.3mL//kg 14.54.0mL//kg 88.6146.1mL/kg 11524mL/kg 8.9 6.5mL//kg 83.1mL/kg 17
18
VIII. 19
20
21
22
23
24
IX. 25
X. 26
27
XI. XII. Cerezyme Cerezyme Cerezyme Cerezyme Cerezyme Cerezyme Cerezyme 1994 5 1994 8 1997 2 199711 1998 1 1999 5 2000 4 XIII. 28