公开(公告)号：WO2017079750A1

公开(公告)日：2017-05-11

申请号：PCT/US2016/060840

申请日：2016-11-07

Applicant: THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK

Inventor： FUTCHER, Bruce ,  GARDIN, Justin ,  SKIENA, Steve ,  YUROVSKY, Alisa ,  WIMMER, Eckard ,  MUELLER, Steffen

IPC: A61K39/12 ,  C12N7/04 ,  A61P31/12

CPC classification number: C12N7/00

Abstract: This invention provides a modified protein encoding sequence containing nucleotide substitutions at multiple locations in the protein encoding sequence, wherein the substitutions introduce rare hexamers. These hexamers may be Frame Dependent, or depleted in only the reading frame, or Frame Independent, or depleted in all three frames. Modified protein encoding sequences of the present invention may include modified viruses useful for vaccines.

Abstract translation: 本发明提供了在蛋白质编码序列中的多个位置含有核苷酸取代的修饰的蛋白质编码序列，其中所述置换引入稀有六聚体。 这些六聚体可以是依赖于框架的，或者仅在阅读框架中消耗，或者与框架无关，或者在所有三个框架中耗尽。 本发明的修饰蛋白质编码序列可以包括用于疫苗的修饰病毒。

公开(公告)号：WO2016037187A1

公开(公告)日：2016-03-10

申请号：PCT/US2015/048985

申请日：2015-09-08

Applicant: THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK

Inventor： WIMMER, Eckard ,  MUELLER, Steffen ,  FUTCHER, Bruce ,  SHEN, Sam ,  STAUFT, Charles ,  WARD, Charles

IPC: C12N7/00 ,  C12N7/01 ,  A61K39/12 ,  A01N65/00

CPC classification number: C12N7/00 ,  A61K39/12 ,  A61K2039/5254 ,  C12N2760/12234 ,  C12N2760/12262 ,  C12N2760/20062 ,  C12N2770/24121 ,  C12N2770/24122 ,  C12N2770/24134 ,  C12N2770/24162 ,  C12N2800/22 ,  Y02A50/386

Abstract: This invention provides an attenuated virus comprising a modified viral genome engineered to containing multiple nucleotide substitutions that reduce the codon pair bias of a virus protein encoding sequence relative to a first host while the codon pair bias relative to a second host is not substantially reduced. In another embodiment, the invention provides an attenuated virus comprising modified viral genome engineered to containing multiple nucleotide substitutions that reduce the codon pair bias of a virus protein-encoding sequence relative to a first host and a second host. The attenuated virus may be used in a vaccine composition for inducing a protective immune response in a subject. The invention also provides a method of synthesizing the attenuated virus. Further, this invention further provides a method for preventing a subject from becoming afflicted with a virus-associated disease comprising administering to the subject a prophylactically effective dose of a vaccine composition comprising the attenuated virus.

Abstract translation: 本发明提供了一种减毒病毒，其包含经工程改造以包含多个核苷酸取代的经修饰的病毒基因，所述多核苷酸取代相对于第一宿主减少病毒蛋白编码序列的密码子对偏差，而相对于第二宿主的密码子对偏差基本上不降低。 在另一个实施方案中，本发明提供了包含修饰的病毒基因组的减毒病毒，其工程改造成含有相对于第一宿主和第二宿主减少病毒蛋白编码序列的密码子对偏差的多个核苷酸取代。 减毒病毒可以用于疫苗组合物中以在受试者中诱导保护性免疫应答。 本发明还提供了合成减毒病毒的方法。 此外，本发明进一步提供了一种用于预防受试者患有病毒相关疾病的方法，包括向受试者施用预防有效剂量的包含减毒病毒的疫苗组合物。

公开(公告)号：WO2014145290A1

公开(公告)日：2014-09-18

申请号：PCT/US2014/030027

申请日：2014-03-15

Applicant: THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK

Inventor： MUELLER, Steffen ,  WIMMER, Eckard ,  FUTCHER, Bruce ,  SKIENA, Steven ,  YANG, Chen

IPC: A61P31/16 ,  C12N7/04

CPC classification number: C12N7/00 ,  A61K39/145 ,  C12N2760/16034 ,  C12N2760/16061 ,  C12N2760/16134 ,  C12N2760/16162

Abstract: This invention provides highly attenuated influenza viruses and vaccines. The attenuated viruses and vaccines proliferate well and have high safety factors. The attenuated viruses providing protective immunity from challenge by virus of the same subtype, as well as cross protection against heterologous viruses.

Abstract translation: 本发明提供高度减毒的流感病毒和疫苗。 减毒病毒和疫苗增殖良好，安全性高。 减毒病毒提供保护性免疫，免受相同亚型病毒的攻击，以及针对异源病毒的交叉保护。