Heterogeneity of Monoclonal Antibodies(19)

low level Tyr to Gln sequence variant in a recombinant antibody.Bio/technology11:1293–1297.

zar AC,Kloczewiak MA,Mazsaroff I.2004.

Matrix-assisted laser desorption/ionization mass spectrometry for the evaluation of the C-terminal lysine distribution of a recombinant monoclonal antibody.Rapid Commun Mass Spectrom18:239–244.

165.Harris RJ.1995.Processing of C-terminal lysine and arginine residues of proteins isolated from mammalian cell culture.J Chromatogr A705: 129–134.

166.Wakankar AA,Borchardt RT,Eigenbrot C,Shia S, Wang YJ,Shire SJ,Liu JL.2007.Aspartate iso-merization in the complementarity-determining regions of two closely related monoclonal antibo-dies.Biochemistry46:1534–1544.(Epub2007Jan 1517.)

167.Wright HT.1991.Nonenzymatic deamidation of asparaginyl and glutaminyl residues in proteins.

Crit Rev Biochem Mol Biol26:1–52.

168.Manning MC,Patel K,Borchardt RT.1989.Sta-bility of protein pharmaceuticals.Pharm Res 6:903–918.

169.Geiger T,Clarke S.1987.Deamidation,isomeriza-tion,and racemization at asparaginyl and aspartyl residues in peptides.Succinimide-linked reactions that contribute to protein degradation.J Biol Chem262:785–794.

170.Kwong MY,Harris RJ.1994.Identification of succinimide sites in proteins by N-terminal sequence analysis after alkaline hydroxylamine cleavage.Protein Sci3:147–149.

171.Stephenson RC,Clarke S.1989.Succinimide for-mation from aspartyl and asparaginyl peptides as

a model for the spontaneous degradation of pro-

teins.J Biol Chem264:6164–6170.

172.Robinson NE,Robinson AB.2001.Molecular clocks.Proc Natl Acad Sci USA98:944–949. 173.Clarke S.1987.Propensity for spontaneous succi-nimide formation from aspartyl and asparaginyl residues in cellular proteins.Int J Pept Protein Res30:808–821.

174.Xie M,Schowen RL.1999.Secondary structure and protein deamidation.J Pharm Sci88: 8–13.

175.Patel K,Borchardt RT.1990.Chemical pathways of peptide degradation.II.Kinetics of deamidation of an asparaginyl residue in a model hexapeptide.

Pharm Res7:703–711.

176.Song Y,Schowen RL,Borchardt RT,Topp EM.

2001.Effect of‘pH’on the rate of asparagine deamidation in polymeric formulations:‘pH’-rate profile.J Pharm Sci90:141–156.

177.Stratton LP,Kelly RM,Rowe J,Shively JE,Smith DD,Carpenter JF,Manning MC.2001.Control-ling deamidation rates in a model peptide:Effects

of temperature,peptide concentration,and addi-tives.J Pharm Sci90:2141–2148.

178.Robinson AB,Scotchler JW,McKerrow JH.1973.

Rates of nonenzymatic deamidation of glutaminyl and asparaginyl residues in pentapeptides.J Am Chem Soc95:8156–8159.

179.Wakankar AA,Liu J,Vandervelde D,Wang YJ, Shire SJ,Borchardt RT.2007.The effect of coso-lutes on the isomerization of aspartic acid residues and conformational stability in a monoclonal anti-body.J Pharm Sci96:1708–1718.

180.Deisenhofer J.1981.Crystallographic refinement and atomic models of a human Fc fragment and its complex with fragment B of protein A from Sta-phylococcus aureus at2.9-and2.8-A resolution.

Biochemistry20:2361–2370.

181.Thies MJ,Mayer J,Augustine JG,Frederick CA, Lilie H,Buchner J.1999.Folding and asso-ciation of the antibody domain C H3:Prolyl iso-merization preceeds dimerization.J Mol Biol 293:67–79.

182.Lilie H,Rudolph R,Buchner J.1995.Association of antibody chains at different stages of folding: Prolyl isomerization occurs after formation of qua-ternary structure.J Mol Biol248:190–201. 183.Shen JF,Kwong YM,Keck GR,Harris JR.1996.

The application of tert-Butylhydroperoxide oxidi-zation to study sites of potential methionine oxi-dization in a recombinant antibody.Tech Protein Chem VII VII:275–284.

m XM,Yang JY,Cleland JL.1997.Antioxidants for prevention of methionine oxidation in recom-binant monoclonal antibody H ER2.J Pharm Sci 86:1250–1255.

185.Chumsae C,Gaza-Bulseco G,Sun J,Liu H.2007.

Comparison of methionine oxidation in thermal stability and chemically stressed samples of a fully human monoclonal antibody.J Chromatogr

B Analyt Technol Biomed Life Sci850:285–

294.

186.Wei Z,Feng J,Lin HY,Mullapudi S,Bishop E, Tous GI,Casas-Finet J,Hakki F,Strouse R,Sche-nerman MA.2007.Identification of a single tryp-tophan residue as critical for binding activity in a humanized monoclonal antibody against respira-tory syncytial virus.Anal Chem79:2797–2805.

(Epub2007Feb2724.)

187.Yang J,Wang S,Liu J,Raghani A.2007.Deter-mination of tryptophan oxidation of monoclonal antibody by reversed phase high performance liquid chromatography.J Chromatogr A1156: 174–182.(Epub2007Feb2015.)

188.Kaneshige H.1987.Nonenzymatic glycosylation of serum IgG and its effect on antibody activity in patients with diabetes mellitus.Diabetes36:822–828.

189.Dolhofer R,Siess EA,Wieland OH.1985.None-nzymatic glycation of immunoglobulins leads to an

JOURNAL OF PHARMACEUTICAL SCIENCES,VOL.97,NO.7,JULY2008DOI10.1002/jps 2444LIU ET AL.