2. .., IV , 2013. 2012 . . 9 2012 1Humira $ 9,48 Adalimumab -
2Enbrel - $ 8,37 3Advair/Seretide 4Remicade $ 7,67 Infliximab -
5Rituxan $ 6,94 rituximab , -(Mab Thera)_ 6Crestor 7Lantus $ 6,12
8Herceptin $ 6,08 trastuzumab - 9Avastin $ 5,98 bevacizumab -
10Lipitor J.D. Carroll, Editor-in-Chief, FiercePharma 3. .., IV ,
2013. 0% 60 70% 90 - 95%100 % Muromomab RituximabTrastuzumab
Adalimumab (Ortoclone) (Rituxan) (Herceptin) (Humira) 4. .., IV ,
2013. o M ~ 150 000 o _ MM 180 Da C9H8O4o -- MM 400 Da_ MM - 5 808
Da IgG 1 - 149 000 Dao C6450H9916N1714O2023S38 5. .., IV , 2013. -
IgG Fc IgG Fc - IgG CHO F- , G - , GN , M - 6. .., IV , 2013. mAb
mAb (13F6) ED5011 g 3 g33 g Fc- mAb .L.Zeitlin et al. PNAS 20
(2011) 108: 20690-20694 7. .., IV , 2013. mAb:- N- () Glu GlnN- Glu
mAb:- (Met252Met-c)- Asn 297- - - Asn315 Asp1 - Asn384 Asp2 -
Asn389 Asp- - - 8. .., IV , 2013. - - 9. .., IV , 2013.
EMEA/CHMP/BWP/157653/2007 18 2008 , , 4.3 4.3.1. - ( , , ), , , . .
.4.3.4. , , ( - N-,, , , ..). 10. .., IV , 2013.13. 13.1. : , , , ,
, ,N- - - - 13.2. .14.2. 14.2.1. () - .14.2.2. , . . 11. .., IV ,
2013. ? . - - . 12. .., IV , 2013.- (MS) ppm (parts per million)
5ppm = 0,0005% ppb - (parts per billion) - -15-18 (10 ) (10 ) _ -3,
-6, 9, -12, -15, 18 13. .., IV , 2013. - -- QTOF- - Q- - - 14. ..,
IV , 2013.- - (QTOF-MS) mAbs _ _ - - IgG - - , - mAb - MS MS/MS - -
N- - _ mAbs 15. .., IV , 2013.- Y. Lyubarskaya et al, Anal Biochem
348 (2006) 24-39 16. .., IV , 2013. IgG < 1ppm Clone B _ _ 17.
.., IV , 2013. MS- IgG IgG : 18. .., IV , 2013. 19. .., IV , 2013.
mAbs Quanzhou L. et al, JBC 2011, 286, No 28: 25134-25144 ( AsnT)
+2 8 ; Met, Trp, His ; ( ) Met/Trp 20. .., IV , 2013.BioPharma
Compass , , , . 21. .., IV , 2013. , . 22. .., IV , 2013.
(Bottom-up) Susana Cristobal - MS2DE MS - 100% 23. .., IV , 2013. ,
() - 94% . MS MS/MS 24. .., IV , 2013. MS/MS 150 ETD- -_ _
(Top-down) N- C- - MaXis 4G 25. .., IV , 2013. - -ISID: CID: _
(PTMs) ETD: . PTMs 26. .., IV , 2013. MaXis-ETD CID - ETD - CID ETD
(PTM) 27. .., IV , 2013. - N- - C- (21) Tsybin et al, HUPO 2010 81
124 - 28. .., IV , 2013. - MaXis 4G ESI Q-TOF 100% __ (15-60 )
UltrafleXtreme < 1 MALDI TOF/TOF _ - AmaZon speed ESI Trap &
ETD 29. .., IV , 2013. - Bruker 30. .., IV , 2013. - Bruker 31. ..,
IV , 2013. 1990 199820002006( - -75% 50-60%20%2%)/M12%3%2% 0-M/M
3%40-50%60-75%98% 32. .., IV , 2013. ! : 495 258 39 47.: 8 903 220
20 83 33. .., IV , 2013. 34. .., IV , 2013. 35. .., IV , 2013.
(400+) - (111): rDNA _ rDNA iRNA _ (mAbs) - (300+): - - rDNA mAbs _
.. - R.A. Rader - , BioExecutive International, 2005, 60-65 36. ..,
IV , 2013. : (40 ) (SNPs) , ,15% : - - - - N- - - - (- ) () 37. ..,
IV , 2013. - -Matrix-Assisted Laserdesorption/ Ionisation (MALDI)
Time-Of-Flight (TOF)Electron MultiplierElectrospray Ionisation
(ESI) Quadrupole Multichannel plateElectron Transfer Ionisation
(ETD) Ion Trap Chemical Ionisation (CI) / (-) M + (Matrix)-H MH+ +
(Matrix)- 38. .., IV , 2013. ESI-Q TOF Bruker 39. .., IV , 2013.
40. .., IV , 2013. - 783.455 QTOF 784.465 785.475 783.6Q 41. .., IV
, 2013. 42. .., IV , 2013. 43. .., IV , 2013. ETD electron transfer
dissociation - ETD ETD -, ,, -, 44. .., IV , 2013. Collision
Induced Dissociation - CID Ar He (PTMs) - b & yElectron
Transfer Dissociation - ETD -_ PTMs - c & z 45. .., IV , 2013.
ETD- 46. .., IV , 2013. IgG Intens. +MS, 4.6-4.8min, Deconvoluted
(MaxEnt)*3000** + 57Da5751124.98522000 * 51068.780610000 51000
51100 51200 51300 51400 51500 51600 m/zqTOF _ 47. .., IV , 2013.
ETD- [M+2H]2+1301.6 IgG32603.2z9 z8 z7 z6 z5z4z3 Side chain
cleavage of N-glyc AsnGlu-Gln-Gln-Phe-Asn-Ser-Thr-Phe-Arg
CH3C=ONHz9.2560.1 2587.1 x5 z4.z5. z3.As1099.4n z8. 408.2
z6.z7.2458.02330.0 2201.9 708.4 495.2 1041.42054.9 687.5 927.4
2403.1 516.3400800 12001600 20002400 m/zManfred Wuhrer Leiden
University Medical Center 48. .., IV , 2013. qTOF MS/MS N- N-
M.Wuhrer et al Glycoproteomics based on tandem mass spectrometry of
glycopeptides J Chrom B 2007, 849 115-1289 49. .., IV , 2013. 1
2345 11 100 %74 %69 % 29 %28 %3% , 50. .., IV , 2013. IgG 51. ..,
IV , 2013. - Compass HPLC U-HPLC - Compass/ Data Analysis SW, :
SmartFormula (3D) QuantAnalysis LibrarySearch MS, MS/MS c -
ProfileAnalysis LC-MS - TargetAnalysis () - ProteinScape - () 52.
.., IV , 2013. MaXis impact - - - _ _(50 /) 20 40 000 m/z _ __ _ -
_ _ (5 ) - _ - 40 000; 1 ppm (. _ ) 53. .., IV , 2013.
TargetAnalysis C _ _ _ (__ ) _
