[发明专利]肿瘤治疗性疫苗CTP37CRM197免疫原及其制备方法与应用无效
| 申请号： | 200710014693.X | 申请日： | 2007-06-01 |
| 公开（公告）号： | CN101314619A | 公开（公告）日： | 2008-12-03 |
| 发明（设计）人： | 王栋海;李磊;王晶翼 | 申请（专利权）人： | 齐鲁制药有限公司 |
| 主分类号： | C07K19/00 | 分类号： | C07K19/00;A61K39/02;A61P35/00 |
| 代理公司： | 济南金迪知识产权代理有限公司 | 代理人： | 王绪银 |
| 地址： | 250100山东*** | 国省代码： | 山东;37 |
| 权利要求书： | 查看更多 | 说明书： | 查看更多 |
| 摘要： | |||
| 搜索关键词： | 肿瘤 治疗 疫苗 ctp37crm197 免疫原 及其 制备 方法 应用 | ||
1.一种免疫原CTP37CRM197，其特征是以白喉毒素突变体CRM197为载体蛋白，通过异型双功能交联剂ε-马来酰亚胺基己酸N-羟基琥珀酰亚胺酯与人绒毛膜促性腺激素β亚基C末端37个氨基酸分子组成的肽CTP37分子相交联而得的CTP37CRM197，每个CRM197分子上交联15-20个CTP37分子；其中，所述的CTP37分子的氨基酸序列如下：
Thr-Cys-Asp-Asp-Pro-Arg-Phe-Gln-Asp-Ser-Ser-Ser-Ser-Lys-Ala-Pro-Pro-Pro-Ser-Leu-Pro-Ser-Pro-Ser-Arg-Leu-Pro-Gly-Pro-Ser-Asp-Thr-Pro-Ile-Leu-Pro-Gln
所述的白喉毒素突变体CRM197的氨基酸序列如下：
Met Gly Ala Asp Asp Val Val Asp Ser Ser Lys Ser Phe Val Met Glu Asn Phe Ser Ser
1 5 10 15 20
Tyr His Gly Thr Lys Pro Gly Tyr Val Asp Ser Ile Gln Lys Gly Ile Gln Lys Pro Lys
21 25 30 35 40
Ser Gly Thr Gln Gly Asn Tyr Asp Asp Asp Trp Lys Glu Phe Tyr Ser Thr Asp Asn Lys
41 45 50 55 60
Tyr Asp Ala Ala Gly Tyr Ser Val Asp Asn Glu Asn Pro Leu Ser Gly Lys Ala Gly Gly
61 65 70 75 80
Val Val Lys Val Thr Tyr Pro Gly Leu Thr Lys Val Leu Ala Leu Lys Val Asp Asn Ala
81 85 90 95 100
Glu Thr Ile Lys Lys Glu Leu Gly Leu Ser Leu Thr Glu Pro Leu Met Glu Gln Val Gly
101 105 110 115 120
Thr Glu Glu Phe Ile Lys Arg Phe Gly Asp Gly Ala Ser Arg Val Val Leu Ser Leu Pro
121 125 130 135 140
Phe Ala Glu Gly Ser Ser Ser Val Glu Tyr Ile Asn Asn Trp Glu Gln Ala Lys Ala Leu
141 145 150 155 160
Ser Val Glu Leu Glu Ile Asn Phe Glu Thr Arg Gly Lys Arg Gly Gln Asp Ala Met Tyr
161 165 170 175 180
Glu Tyr Met Ala Gln Ala Cys Ala Gly Asn Arg Val Arg Arg Ser Val Gly Ser Ser Leu
181 185 190 195 200
Ser Cys Ile Asn Leu Asp Trp Asp Val Ile Arg Asp Lys Thr Lys Thr Lys Ile Glu Ser
201 205 210 215 220
Leu Lys Glu His Gly Pro Ile Lys Asn Lys Met Ser Glu Ser Pro Asn Lys Thr Val Ser
22l 225 230 235 240
Glu Glu Lys Ala Lys Gln Tyr Leu Glu Glu Phe His Gln Thr Ala Leu Glu His Pro Glu
241 245 250 255 260
Leu Ser Glu Leu Lys Thr Val Thr Gly Thr Asn Pro Val Phe Ala Gly Ala Asn Tyr Ala
261 265 270 275 280
Ala Trp Ala Val Asn Val Ala Gln Val Ile Asp Ser Glu Thr Ala Asp Asn Leu Glu Lys
281 285 290 295 300
Thr Thr Ala Ala Leu Ser Ile Leu Pro Gly Ile Gly Ser Val Met Gly Ile Ala Asp Gly
301 305 310 315 320
Ala Val His His Asn Thr Glu Glu Ile Val Ala Gln Ser Ile Ala Leu Ser Ser Leu Met
321 325 330 335 340
Val Ala Gln Ala Ile Pro Leu Val Gly Glu Leu Val Asp Ile Gly Phe Ala Ala Tyr Asn
341 345 350 355 360
Phe Val Glu Ser Ile Ile Asn Leu Phe Gln Val Val His Asn Ser Tyr Asn Arg Pro Ala
361 365 370 375 380
Tyr Ser Pro Gly His Lys Thr Gln Pro Phe Leu His Asp Gly Tyr Ala Val Ser Trp Asn
381 385 390 395 400
Thr Val Glu Asp Ser Ile Ile Arg Thr Gly Phe Gln Gly Glu Ser Gly His Asp Ile Lys
401 405 410 415 420
Ile Thr Ala Glu Asn Thr Pro Leu Pro Ile Ala Gly Val Leu Leu Pro Thr Ile Pro Gly
421 425 430 435 440
Lys Leu Asp Val Asn Lys Ser Lys Thr His Ile Ser Val Asn Gly Arg Lys Ile Arg Met
441 445 450 455 460
Arg Cys Arg Ala Ile Asp Gly Asp Val Thr Phe Cys Arg Pro Lys Ser Pro Val Tyr Val
461 465 470 475 480
Gly Asn Gly Val His Ala Asn Leu His Val Ala Phe His Arg Ser Ser Ser Glu Lys Ile
481 485 490 495 500
His Ser Asn Glu Ile Ser Ser Asp Ser Ile Gly Val Leu Gly Tyr Gln Lys Thr Val Asp
501 505 510 515 520
His Thr Lys Val Asn Ser Lys Leu Ser Leu Phe Phe Glu Ile Lys Ser
521 525 530 535。
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