CN100448893C - 识别β淀粉样肽的人源化抗体 - Google Patents
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Abstract
Description
处理组 | N<sup>a</sup> | 处理抗体 | 抗体特异性 | 抗体同种型 |
1 | 9 | 无(仅PBS) | NA<sup>b</sup> | NA |
2 | 10 | 多克隆 | Aβ1-42 | 混合的 |
3 | 0 | mAb<sup>d</sup>2H3 | Aβ1-12 | IgG1 |
4 | 8 | mAb10D5 | Aβ3-7 | IgG1 |
5 | 6 | mAb266 | Aβ13-28 | IgG1 |
6 | 8 | mAb21F12 | Aβ33-42 | IgG2a |
周21F12 | 21F12 | 周10D5 | 10D5 | 周多克隆 | 多克隆 |
0.150.511.5233.5456789101112131415161718192022232425262728 | 500800250018001400600055016009253300400014001900170016001000150013001000170017005000900300175016001000110022501400 | 0.150.511.11.2233.5456789101112131415161718192022232425262728 | 300014000500050001300300040005002400925170016004000180018002300210028001900270013002200220025009802000100085060011001450 | 0.150.511.5233.5456789101112131415161718192022232425262728 | 160040004500300013001600650130045021001300230070060060010009001900120070021001800180012001000120067585016001900 |
DNA | 大小 | 编码链? | DNA序列 | 备注 |
3806 | 40 | 是 | ACT.AGT.CGA.CAT.GAA.GTT.GCC.TGT.TAG.GCT.GTT.GGT.GCT.G(SEQID NO:39) | 小鼠κ可变引物1MKV引物1,MRC对;%A+T=50.00[20];%C+G=50.00[20]Davis,Botstein,Roth解链温度72.90℃ |
3807 | 39 | 是 | ACT.AGT.CGA.CAT.GGA.GWC.AGA.CAC.ACT.CCT.GYT.ATG.GGT(SEQID NO:40) | 小鼠κ可变引物2MKV引物2,MRC对%A+T=46.15[18];%C+G=48.72[19]Davis,Botstein,Roth解链温度72.05℃ |
3808 | 40 | 是 | ACT.AGT.CGA.CAT.GAG.TGT.GCT.CAC.TCA.GGT.CCT.GGS.GTT.G(SEQID NO:41) | 小鼠κ可变引物3MKV引物3,MRC对;%A+T=45.00[18];%C+G=52.50[21]Davis,Botstein,Roth解链温度73.93℃ |
3809 | 43 | 是 | ACT.AGT.CGA.CAT.GAG.GRC.CCC.TGC.TCA.GWT.TYT.TGG.MWT.CTT.G(SEQ ID NO:42) | 小鼠κ可变引物4MKV引物4,MRC对;%A+T=41.86[18];%C+G |
=46.51[20]Davis,Botstein,Roth解链温度72.34℃ | ||||
3810 | 40 | 是 | ACT.AGT.CGA.CAT.GGA.TTT.WCA.GGT.GCA.GAT.TWT.CAG.CTT.C(SEQ ID NO:43) | 小鼠κ可变引物5MKV引物5,MRC对%A+T=52.50[21];%C+G=42.50[17]Davis,Botstein,Roth解链温度69.83℃ |
3811 | 37 | 是 | ACT.AGT.CGA.CAT.GAG.GTK.CYY.TGY.TSA.GYT.YCT.GRG.G(SEQ IDNO:44) | 小鼠κ可变引物6MKV引物6,MRC对;%A+T=37.84[14];%C+G=40.54[15]Davis,Botstein,Roth解链温度68.01℃ |
3812 | 41 | 是 | ACT.AGT.CGA.CAT.GGG.CWT.CAA.GAT.GGA.GTC.ACA.KWY.YCW.GG(SEQ ID NO:45) | 小鼠κ可变引物7MKV引物7,MRC对;%A+T=39.02[16];%C+G=46.34[19]Davis,Botstein,Roth解链温度71.70℃ |
3813 | 41 | 是 | ACT.AGT.CGA.CAT.GTG.GGG.AYC.TKT.TTY.CMM.TTT.TTC.AAT.TG(SEQID NO:46) | 小鼠κ可变引物8MKV引物8,MRC对;%A+T=53.66[22];%C+G=34.15[14]Davis,Botstein,Roth解链温度66.70℃ |
3814 | 35 | 是 | ACT.AGT.CGA.CAT.GGT.RTC.CWC.ASC.TCA.GTT.CCT.TG(SEQ ID NO:47) | 小鼠κ可变引物9MKV引物9,MRC对.%A+T=45.71[16];%C+G=45.71[16]Davis,Botstein,Roth解链温度69.36℃ |
3815 | 37 | 是 | ACT.AGT.CGA.CAT.GTA.TAT.ATG.TTT.GTT.GTC.TAT.TTC.T(SEQ IDNO:48) | 小鼠κ可变引物10MKV引物10,MRC对;%A+T=70.27[26];%C+G=29.73[11]Davis,Botstein,Roth解链温度63.58℃ |
3816 | 38 | 是 | ACT.AGT.CGA.CAT.GGA.AGC.CCC.AGC.TCA.GCT.TCT.CTT.CC(SEQ ID | 小鼠κ可变引物11MKV引物11,MRC对; |
NO:49) | %A+T=44.74[17];%C+G=55.26[21]Davis,Botstein,Roth解链温度74.40℃ | |||
3817 | 27 | 否 | GGA.TCC.CGG.GTG.GAT.GGT.GGG.AAG.ATG(SEQ ID NO:50) | 小鼠κ轻链反向引物,第116-122位氨基酸;Ck恒定区引物,MRC对+SmaI位点;%A+T=47.06[8];%C+G=52.94[9]Davis,Botstein,Roth解链温度57.19℃ |
3818 | 37 | 是 | ACT.AGT.CGA.CAT.GAA.ATG.CAG.CTG.GGT.CAT.STT.CTT.C(SEQ IDNO:51) | 小鼠重链可变引物1MHV引物1,MRC对; |
3819 | 36 | 是 | ACT.AGT.CGA.CAT.GGG.ATG.GAG.CTR.TAT.CAT.SYT.CTT(SEQ IDNO:52) | 小鼠重链可变引物2MHV引物2,MRC对; |
3820 | 37 | 是 | ACT.AGT.CGA.CAT.GAA.GWT.GTG.GTT.AAA.CTG.GGT.TTT.T(SEQ IDNO:53) | 小鼠重链可变引物3MHV引物3,MRC对; |
3821 | 35 | 是 | ACT.AGT.CGA.CAT.GRA.CTT.TGG.GYT.CAG.CTT.GRT.TT(SEQ ID NO:54) | 小鼠重链可变引物4MHV引物4,MRC对; |
3822 | 40 | 是 | ACT.AGT.CGA.CAT.GGA.CTC.CAG.GCT.CAA.TTT.AGT.TTT.CCT.T(SEQID NO:55) | 小鼠重链可变引物5MHV引物5,MRC对; |
3823 | 37 | 是 | ACT.AGT.CGA.CAT.GGC.TGT.CYT.RGS.GCT.RCT.CTT.CTG.C(SEQ IDNO:56) | 小鼠重链可变引物6MHV引物6,MRC对; |
3824 | 36 | 是 | ACT.AGT.CGA.CAT.GGR.ATG.GAG.CKG.GRT.CTT.TMT.CTT(SEQ IDNO:57) | 小鼠重链可变引物7MHV引物7,MRC对; |
3825 | 33 | 是 | ACT.AGT.CGA.CAT.GAG.AGT.GCT.GAT.TCT.TTT.GTG(SEQ ID NO:58) | 小鼠重链可变引物8MHV引物8,MRC对; |
3826 | 40 | 是 | ACT.AGT.CGA.CAT.GGM.TTG.GGT.GTG.GAM.CTT.GCT.ATT.CCT.G(SEQID NO:59) | 小鼠重链可变引物9MHV引物9,MRC对; |
3827 | 37 | 是 | ACT.AGT.CGA.CAT.GGG.CAG.ACT.T | 小鼠重链可变引物10 |
AC.ATT.CTC.ATT.CCT.G(SEQ IDNO:60) | MHV引物10,MRC对; | |||
3828 | 38 | 是 | ACT.AGT.CGA.CAT.GGA.TTT.TGG.GCT.GAT.TTT.TTT.TAT.TG(SEQ IDNO:61) | 小鼠重链可变引物11MHV引物11,MRC对; |
3829 | 37 | 是 | ACT.AGT.CGA.CAT.GAT.GGT.GTT.AAG.TCT.TCT.GTA.CCT.G(SEQ IDNO:62) | 小鼠重链可变引物12MHV引物12,MRC对; |
3832 | 27 | 否 | GGA.TCC.CGG.GAG.TGG.ATA.GAC.tGA.TGG(SEQ ID NO:63) | mouse IgG2b重链反向引物第119-124位氨基酸,MRC对; |
浓度(μg/ml) | 3D6 | PK1614 | IgG1 |
0.0370.110.331 | 118.699.798.63 | 119.3118.971.2584.53 | 134.4 |
变化 | VL(112残基) | VH(119残基) |
Hu->Mu:构架 | 4/112 | 3/119(1规范,1包装) |
CDR1 | 6/16 | 3/5 |
CDR2 | 4/7 | 7/14 |
CDR3 | 5/8 | 4/10 |
Hu->Mu | 19/112(17%) | 17/119(14%) |
Mu->Hu:构架 | 13/112 | 14/119 |
回复突变注解 | 1.I2V其是一个规范的位置2.Y36L其是一个包装残基且也位于CDR的下方3.L46R其是一个包装残基且也位于CDR的下方 | 4.S49A游标/在CDRs下方.5.A93V其是包装和游标区残基6.K94R是一个规范的残基 |
受体注解 | 7.KABID 019230/GenbankAcc#S403428.HukLc亚组II9.CDR来自相同的规范的结构组作为供体(m3D6)L1=4型L2=1型L3=1型10.未知的特异性 | 11.KABID045919/GenbankAcc#AF11511012.Hu HC亚组III13.CDRs来自相同的规范的结构组作为供体(m3D6)H1=1型H2=3型识别脑膜炎奈瑟氏球菌(Neisseria meningitidis)的荚膜多糖 |
受体种系 | 15.VH3-23 | 16.A3&A19 |
DNA# | 大小 | 编码? | 序列 | 注解 |
4060 | 136 | 是 | tccgc aagct tgccg ccacc ATGGACATGC GCGTG CCCGC CCAGCTGCTG GGCCT GCTGA TGCTGTGGGT GTCCG GCTCC TCCGGCTACG TGGTG ATGAC CCAGTCCCCC CTGTC CCTGC CCGTGACCCC CGGCG A(SEQ ID NO:17) | 人3D6VL-A |
4061 | 131 | 否 | CTGGG GGGAC TGGCC GGGCTTCTGC AGCAG CCAGT TCAGGTAGGT CTTGC CGTCG GAGTCCAGCA GGGAC TGGGA GGACTTGCAG GAGAT GGAGG CGGGCTCGCC GGGGG TCACG GGCAGGGACA GGGGG G(SEQ ID NO:18) | 人3D6VL-B |
4062 | 146 | 是 | ACCTG AACTG GCTGC TGCAGAAGCC CGGCC AGTCC CCCCAGCGCC TGATC TACCT GGTGTCCAAG CTGGA CTCCG GCGTGCCCGA CCGCT TCTCC GGCTCCGGCT CCGGC ACCGA CTTCACCCTG AAGAT CTCCC GCGTGGAGGC C(SEQ ID NO:19) | 人3D6VL-C |
4063 | 142 | 否 | aattc tagga tccac tcacg CTTGATCTCC ACCTT GGTGC CCTGGCCGAA GGTGC GGGGG AAGTGGGTGC CCTGC CAGCA GTAGTACACG CCCAC GTCCT CGGCCTCCAC GCGGG AGATC TTCAGGGTGA AGTCG GTGCC GG(SEQID NO:20) | 人3D6VL-D |
4064 | 16 | 否 | CTGGG GGGAC TGGCC G(SEQ ID NO:21) | 人3D6VL A+B反向%A+T=18.75[3];%C+G=81.2[13]Davis,Botstein,Roth解链温度66.96℃ |
4065 | 22 | 是 | ACCTG AACTG GCTGC TGCAGAA(SEQ ID NO:22) | 人3D6VL C+D正向%A+T=45.45[10];%C+G=54.55[12]Davis,Botstein,Roth解链温度64.54℃ |
4066 | 138 | 是 | acaga aagct tgccg ccacc ATGGA | 人3D6VH-A |
GTTTG GGCTG AGCTG GCTTTTTCTT GTGGC TATTT TAAAAGGTGT CCAGT GTGAG GTGCAGCTGC TGGAG TCCGG CGGCGGCCTG GTGCA GCCCG GCGGCTCCCT GCGCC TGT(SEQ ID NO:23) | ||||
4067 | 135 | No | GCCGC CGGAG CGGAT GGAGGCCACC CACTC CAGGC CCTTGCCGGG GGCCT GGCGC ACCCAGGACA TGCCG TAGTT GGAGAAGGTG AAGCC GGAGG CGGCGCAGGA CAGGC GCAGG GAGCCGCCGG GCTGC ACCAG(SEQ ID NO:24) | 人3D6VH-B |
4068 | 142 | 是 | CTGGA GTGGG TGGCC TCCATCCGCT CCGGC GGCGG CCGCACCTAC TACTC CGACA ACGTGAAGGG CCGCT TCACC ATCTCCCGCG ACAAC GCCAA GAACTCCCTG TACCT GCAGA TGAACTCCCT GCGCG CCGAG GACACCG(SEQ ID NO:25) | 人3D6VH-C |
4069 | 144 | 否 | ctgca aggat ccact caccG GAGGACACGG TCACC AGGGT GCCCTGGCCC CAGTA GTCGG AGGAGCCGGA GTAGT GGTCG TAGCGCACGC AGTAG TACAG GGCGGTGTCC TCGGC GCGCA GGGAGTTCAT CTGCA GGTACAGGG(SEQ ID NO:26) | 人3D6VH-D |
4070 | 16 | 否 | GCCGC CGGAG CGGAT G(SEQ ID NO:27) | 人3D6VH A+B反向%A+T=18.75[3];%C+G=81.25[13]Davis,Botstein,Roth解链温度66.96℃ |
4071 | 20 | 是 | CTGGA GTGGG TGGCC TCCAT(SEQ ID NO:28) | 人3D6VH C+D正向%A+T=35.00[7];%C+G=65.00[13]Davis,Botstein,Roth解链温度66.55℃ |
4072 | 19 | 是 | tcc gca agc ttg ccg cca c(SEQ IDNO:29) | 人3D6VL A+B正向%A+T=31.58[6];%C+G=68.42[13]Davis,Botstein, |
Roth解链温度66.64℃ | ||||
4073 | 29 | 否 | aat tct agg atc cac tca cgC TTG ATCTC(SEQ ID NO:30) | 人3D6VL C+D反向%A+T=55.17[16];%C+G=44.83[13]Davis,Botstein,Roth解链温度66.04℃ |
4074 | 23 | 是 | aca gaa agc ttg ccg cca ccA TG(SEQ ID NO:31) | 人3D6VH A+B正向%A+T=43.48[10];%C+G=56.52[13]Davis,Botstein,Roth解链温度66.33℃ |
4075 | 22 | 否 | ctg caa gga tcc act cac cGG A(SEQ ID NO:32) | 人3D6VH C+D反向%A+T=40.91[9];%C+G=59.09[13]Davis,Botstein,Roth解链温度66.40℃ |
ng/ml | 嵌合的 | hu VH/ChVL | ChVH/HuVL | Hu VH/HuVL |
69060026023020019087776763292522219.68.57.473.22.3 | 0.830.6750.450.2510.129 | 0.8110.6480.4380.2320.124 | 0.8670.7740.5940.3810.198 | 0.8950.810.6890.4960.278 |
抗体 | ka1(1/Ms) | kd1(1/s) | Kd(nM) |
Mu 3D6 | 4.06E+05 | 3.57E-04 | 0.88 |
嵌合3D6 | 4.58E+05 | 3.86E-04 | 0.84 |
Hu 3D6v1 | 1.85E+05 | 3.82E-04 | 2.06 |
Hu 3D6v2 | 1.70E+05 | 3.78E-04 | 2.24 |
M3D6 | DAE13 | Hu3D6 |
30389.1121713418.218678.92724126398.827924.812008.429487.825498.6965224599.32924011922.717443.1 | 17463.913200.636284.7421.31970224855.829287.412733.127722.530460.723320.17119.128093.524659.726748.9 | 40963.824202.212472.433851.827187.329016.933830.726734.930144.535126.928414.816956.118190.725671.4 |
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