??????(Erythropoietin, EPO)

1
????????????
2
??????????
3
???????????
4
??????(Erythropoietin, EPO)

• EPO?1906????,?????????,??????????????,????????????
  ???(Erythroid progenitor cells),??????????????(Fun
  ctional erythroblasts)?
• ????????????,?90????????,??10??,????????????(Hem
  angioblastomas)????????

5
???????????

• Recombinant EPO?1985???????,1989??????????????????
  ??????????
• 1990?????????AIDS????AZT????????
• 1995?FDA??recombinant EPO?????????????
• ?????????????

6
EPO????

• 2005???????100???,???????????1/4?,???Amgen,
  Johnson Johnson ?Roche?????????
• ??????25??????,????68?????,?????17???????,??????
  EPO???????????

7
???(Interferons, IFN)

• 1957?????????????????????????????-IFN,????????????
  ?????????
• IFN??????????,????????????,?????????????,?????????
  ???????????
• IFN???????????????????????????,???????????????????

8
??????

• ??IFN?????????????,??????????(leukocyte),?????????
  ,?????????,???????????1001,000??????,???,??????
• 1980???Genentech?????????????????????,12?????20??
  ?????,??????????????????????

9
????????

• ????????,??18??, ???, ????????
• IFN ?1b ?????
• IFN ?2a ?????,??
• IFN ?2b ?????,??
• IFN ? ??????
• IFN ? ???????

10
????????

• ??????????????17,????60??????
• PEG-?????,??????????,????????????
• ?????Biogen, Schering?Serono?????????

11
???(Insulin)

• Insulin????B????,????????????
• ?????????????????????????,??????,?????????????????
  ,????????

12
???????

• ?????????????,????????????,??????????????
• ?????????????????B30?????,??????????,????????????
  ?????????????????????????????,????????????????????
  ??
• ????????B30?Alanine??Threonine,???????????????
• ????????

13
???????

• ???????????13.2?
• ?????Novo Nordisk?Lilly.

14
????(monoclonal antibody)

• 1975?Dr. George Kohler?Dr. Cesar
  Milstein???????,????????????(cell
  line)?????????????????????????????????????????????
  ?????????,??????????????????????????????,?????????
  ??????????????????????????????????????????????????
  ?,?????????????????

15
????????

• ????????(Murine monoclonal antibodies 100??)?
• ????OrthoClone (Johnson Johnson)?1986?????????
  ?????????????????CD3???

16
????????

• ????????(Murine monoclonal antibodies 100??)?
• ????????(Chimeric monoclonal antibodies30???70?
  ?)?
• ?????????(Humanized monoclonal antibodies
  5-10???90-95??)
• ????????(Human monoclonal antibodies100??)

17
????????(Murine monoclonal antibodies)

• ????OrthoClone (Johnson Johnson)?1986??????????
  ????????????????CD3???

18
??????????????

• ?5080?????????????(a human anti-mouse antibody,
  HAMA),?????????????????????HAMA?????????,?????????
  ?????????????????,????????????????,???????????????
  ?????(anaphylactic shock)?????????
• ???????????????,???20??,????????????,???????
• ???????Fc??????????Fc??????,????????????

19
??????

• ????????HAMA????,??????????Fc????????????????,????
  ????,??????30?????70???????????????10??????1????
  ?????????,????????????????????????
• 1994?Centocor?ReoPro?????????????,???????,1997?IDE
  C/Genentech?Rituxan?????????????,?????10????

20
???????

• ????????,???100?????,????????????????????????????
  ??,???????????????,????????????????
• ?????????????????????,??????CDR???????????,???????
  ????510,????????????????????????????????(a
  human anti-humanized antibody, HAHA),????????12?
  
• 1997?FDA??????????????,Roche/PDL?Zenapax,?????????
  ?????

21
??????

• ???????????
• 1.????????,????????????
• 2.??????????,???????????
• 3.??????????,??????????

22
?????????

• ????225?????????????,???1000????????,??72???????,
  ??????????50,???????18,???13,??????6,?????????
  ?5,?????8,???2008???70?????,??????140????

23
????

• ????????????(anticlotting proteins)?????????
• ?????
• ??????(fibrinolytic enzyme)
• ?????

24
?????

• ????????????????,??????????????(??polysaccharide
  heparin)

25
??????

• ????????????????(debridement),????????????????????
  ?????????????,?????????????????

26
?????

• ????????????????????????????????,???????????,????u
  rokinase, streptokinase, tissue plasminogen
  activator??
• ???(streptokinase)????b-???????
• ???(urokinase)??????????????
• ??????????(tissue plasminogen activator,
  tPA)????????????serine protease,?????????(plasmino
  gen),??????????????(plasmin),?????????????

27
?????(clotting proteins)

• ????????????,???????K?,???????????
• ????(factor VIII)???????????????,????????????,????
  ?A?????
• ????????????Factor VIII,????????????,?????????????
  ,?Factor VIII??????,????????????,?????????????????
  ????????Baxter, Bayer, Aventis, Novo
  Nordisk,?Alpha Therapeutics?
• ???????????????????10.7?

28
????????(colony stimulating factor, CSF)

• ?????????????,?????????????????????????????????,??
  ??????????????????????,?????G-CSF, M-CSF,
  GM-CSF????CSF????????????????????????,????????????
  ????

29
Granulocyte-macrophage colony stimulating factor
(GM-CSF)

• 1977?Burgress????????????????????????????????(GM-C
  SF)?
• T???B????????????????????????????GM-CSF???T???????
  ????????????????????????????????????IL-1?TNF?????
  ??
• GM-CSF?????????Stem cell??Granulocyte?Macrophage,?
  ?????????????????????,????????????????????????????
  ??

30
Granulocyte colony stimulating factor (G-CSF)

• ????TNF-a?IFN-g???????????????????????(G-CSF),??,?
  ???????????????????????LPS, IL-1?TNF-a?????????G-C
  SF?
• GM-CSF?????,?G-CSF?M-CSF??????????,?????,????Monoc
  yte?Granulocyte????
• G-CSF??Neutrophils????????????????????????????????
  ??????????G-CSF?????????,??????????(Leukemia),????
  ?????????????(Congenital agranulocytosis)?

31
Macrophage colony stimulating factor (M-CSF)

• ????????M-CSF,???????????????????????????????????
  ???LPS?????????B???T?????????
• M-CSF???Macrophage???,??????????(Aplastic
  anemia),???Monocyte???????????????????????????????
  ????,??????????????????????????

32
CSF??????

• ?????
• Roche/Amgen (Amgen??) Filgrastim
• Daiichi (Amgen??) Filgrastim
• Aventis (Chugai??) Lenograstim
• Chugai (Chugai??) Lenograstim
• Novartis (GI, Wyeth??) Molgramostim
• Green Cross (Green Cross??) mirimostim
• ?
• CSF???????????8.2?

33
?????(Growth hormone)

• ?????????????,????????,??????????????????,????????
  ????????
• 1985???????????NPA (National Pituitary
  Agency)??,NPA??????????,?????????,1985?4???FDA????
  ????????????,????????????????,??????(Creuz-feld-ja
  cob disease of the brain)????????,Genentech???????
  ?????????,????????
• ????????????????5.1?

34
???(Interleukin)

• ?????(Lymphokines)?????????????,?????????????????(
  Lymphocytes)?????????,??????????????????,?????????
  ???????????????????B???T?????B???????(?????),T????
  ?????(Lymphokines)???B??????

35
???-2 (Interleukin-2, IL-2)

• 1976?Morgan?????????????????????????????,?????????
  ???T??????,??T??????(T cell growth factor, TCGF),
  1979?????????-2????T?????,??????(Malignant
  cell),??????,?????????????????????????
• ????????????,???????????0.6?