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【主权项】
1. 一种嵌合多核苷酸，其包含至少一个人免疫球蛋白（Ig)连接（J)区基因、Ig恒定区 基因和大鼠3'增强子。2. 如权利要求1所述的嵌合多核苷酸，其中所述大鼠3'增强子包括如SEQ ID NO: 1所 示的序列。3. 如前述权利要求中任一项所述的嵌合多核苷酸，其还包含至少一个人Ig可变（V)区 基因和/或人Ig多样性（D)区基因。4. 如前述权利要求中任一项所述的嵌合多核苷酸，其中所述恒定区基因选自由人恒定 区基因和大鼠恒定区基因组成的组。5. 如前述权利要求中任一项所述的嵌合多核苷酸，其中所述恒定区基因包括大鼠恒定 区基因。6. 如前述权利要求中任一项所述的嵌合多核苷酸，其中所述恒定区基因包括选自由 Cy和Cy组成的组的恒定区基因。7. 如前述权利要求中任一项所述的嵌合多核苷酸，其包含与细菌人工染色体（BAC) Annabel或其部分基本同源的核酸序列。8. 如权利要求3-7中任一项所述的嵌合多核苷酸，其中所述人Ig V区包含至少一个可 从BAC6-VH3-11和/或BAC3分离的人V区基因。9. 如前述权利要求中任一项所述的嵌合多核苷酸，其以5'至3'的顺序包含核酸序列 (a)和（b): (a) 人Ig可变区，其包含可从BAC6-VH3-11和/或BAC3分离的呈天然构型的人V区基 因；和 (b) 人Ig连接区，其包含可从所述细菌人工染色体（BAC)Annabel分离的呈天然构型的 人J区基因。10. 如权利要求3-9中任一项所述的嵌合多核苷酸，其中所述人免疫球蛋白可变区、所 述人免疫球蛋白多样性区、所述人免疫球蛋白连接区、所述免疫球蛋白恒定区和所述大鼠 3'增强子中的每一个处于图Ia中所示的相对位置。11. 如权利要求10所述的嵌合多核苷酸，其包含与如SEQ ID NO: 2所示的核酸序列基 本同源的核酸序列。12. 如权利要求10所述的嵌合多核苷酸，其包含与如SEQ ID NO: 11所示的核酸序列基 本同源的核酸序列。13. 如权利要求3-10中任一项所述的嵌合多核苷酸，其中所述V-D-J区重排并形成编 码重链可变结构域的完整外显子。14. 一种啮齿动物细胞，其包含如前述权利要求中任一项所述的嵌合多核苷酸。15. 如权利要求13所述的啮齿动物细胞，其还包含编码功能性免疫球蛋白的多核苷 酸，所述多核苷酸包含V-、J-和恒定区基因以及与选自由SEQ ID NO: 6和SEQ ID NO: 7组 成的组的核酸序列基本同源的核酸序列。
【专利摘要】本发明涉及可用于在啮齿动物中优化产生具有人独特型的功能性免疫球蛋白的多核苷酸，尤其是嵌合多核苷酸。本发明还涉及包含此类多核苷酸的啮齿动物。
【IPC分类】C12N15/85, A01K67/027, C07K16/00
【公开号】CN104994729
【申请号】CN201380070457
【发明人】M·布鲁格曼, R·布洛夫, M·J·奥斯伯恩, B·马
【申请人】Omt公司
【公开日】2015年10月21日
【申请日】2013年12月13日
【公告号】CA2895144A1, EP2931030A2, US20150113668, WO2014093908A2, WO2014093908A3