公开(公告)号：US09238825B2

公开(公告)日：2016-01-19

申请号：US14038704

申请日：2013-09-26

Applicant: MEDIMMUNE, LLC

Inventor： Erich Hoffmann ,  Hong Jin ,  George Kemble ,  Zhongying Chen

IPC: A61K39/145 ,  A61K39/00 ,  A61K39/12 ,  C12P21/04 ,  C12N15/86 ,  C07K14/005 ,  C12N7/00 ,  C12N15/85

CPC classification number: C12N15/86 ,  A61K2039/5254 ,  C07K14/005 ,  C12N7/00 ,  C12N15/85 ,  C12N2760/16122 ,  C12N2760/16134 ,  C12N2760/16143 ,  C12N2760/16162 ,  C12N2760/16222 ,  C12N2760/16234 ,  C12N2760/16243 ,  C12N2760/16262 ,  C12N2840/20

Abstract: Vectors and methods for the production of influenza viruses suitable as recombinant influenza vaccines in cell culture are provided. Bi-directional expression vectors for use in a multi-plasmid influenza virus expression system are provided. Additionally, the invention provides methods of producing influenza viruses with enhanced ability to replicate in embryonated chicken eggs and/or cells (e.g., Vero and/or MDCK) and further provides influenza viruses with enhanced replication characteristics. A method of producing a cold adapted (ca) influenza virus that replicates efficiently at, e.g., 25° C. (and immunogenic compositions comprising the same) is also provided.

公开(公告)号：US20140341948A1

公开(公告)日：2014-11-20

申请号：US14285339

申请日：2014-05-22

Applicant: Icahn School of Medicine at Mount Sinai

Inventor： Peter Palese ,  Adolfo Garcia-Sastre ,  Thomas Muster

IPC: A61K39/145 ,  C12N7/00

CPC classification number: A61K39/145 ,  A61K39/0011 ,  A61K39/12 ,  A61K39/155 ,  A61K39/17 ,  A61K39/205 ,  A61K2039/525 ,  A61K2039/5254 ,  A61K2039/5256 ,  A61K2039/543 ,  A61K2039/552 ,  A61K2039/572 ,  A61K2039/585 ,  C07K14/005 ,  C12N7/00 ,  C12N15/86 ,  C12N2760/16121 ,  C12N2760/16122 ,  C12N2760/16132 ,  C12N2760/16134 ,  C12N2760/16143 ,  C12N2760/16151 ,  C12N2760/16161 ,  C12N2760/16162 ,  C12N2760/16171 ,  C12N2760/16221 ,  C12N2760/16222 ,  C12N2760/16232 ,  C12N2760/16234 ,  C12N2760/16243 ,  C12N2760/16251 ,  C12N2760/16262 ,  C12N2760/16271 ,  C12N2760/18022 ,  C12N2760/18034 ,  C12N2760/18122 ,  C12N2760/18134 ,  C12N2760/18522 ,  C12N2760/18534 ,  C12N2760/20222 ,  C12N2760/20234 ,  Y02A50/466

Abstract: The present invention relates, in general, to attenuated negative-strand RNA viruses having an impaired ability to antagonize the cellular interferon (IFN) response, and the use of such attenuated viruses in vaccine and pharmaceutical formulations. The invention also relates to the development and use of IFN-deficient systems for selection of such attenuated viruses.In particular, the invention relates to attenuated influenza viruses having modifications to the NS1 gene that diminish or eliminate the ability of the NS1 gene product to antagonize the cellular IFN response. The mutant viruses replicate in vivo but demonstrate reduced pathogenicity, and therefore are well suited for live virus vaccines, and pharmaceutical formulations.

Abstract translation: 本发明一般涉及具有拮抗细胞干扰素（IFN）应答能力受损的减毒负链RNA病毒，以及在疫苗和药物制剂中使用这种减毒病毒。 本发明还涉及用于选择这种减毒病毒的IFN-缺陷系统的开发和应用。 具体地，本发明涉及具有修饰的NS1基因的减毒流感病毒，其减少或消除NS1基因产物拮抗细胞IFN应答的能力。 突变体病毒在体内复制但表现出降低的致病性，因此非常适合于活病毒疫苗和药物制剂。

公开(公告)号：US20060252132A1

公开(公告)日：2006-11-09

申请号：US11368246

申请日：2006-03-06

Applicant: Chin-Fen Yang ,  George Kemble ,  Chongguang Liu

Inventor： Chin-Fen Yang ,  George Kemble ,  Chongguang Liu

IPC: C12P19/34 ,  C12N5/06 ,  C12N5/16

CPC classification number: C07K14/005 ,  A61K39/00 ,  A61K39/12 ,  A61K39/145 ,  A61K2039/5254 ,  A61K2039/53 ,  C07H21/04 ,  C12N7/00 ,  C12N9/2402 ,  C12N15/86 ,  C12N2740/16122 ,  C12N2740/16222 ,  C12N2760/16122 ,  C12N2760/16134 ,  C12N2760/16143 ,  C12N2760/16161 ,  C12N2760/16222 ,  C12N2760/16234 ,  C12N2760/16243 ,  C12N2760/16261

Abstract: Polypeptides, polynucleotides, methods, compositions, and vaccines comprising influenza hemagglutinin and neuraminidase variants are provided.

公开(公告)号：US06852522B1

公开(公告)日：2005-02-08

申请号：US09724419

申请日：2000-11-28

Applicant: Peter Palese ,  Adolfo Garcia-Sastre ,  Robert O'Neil

Inventor： Peter Palese ,  Adolfo Garcia-Sastre ,  Robert O'Neil

IPC: C12N15/01 ,  A61K35/76 ,  A61K39/00 ,  A61K39/12 ,  A61K39/145 ,  A61K39/155 ,  A61K39/17 ,  A61K39/205 ,  A61K45/00 ,  A61P31/12 ,  A61P31/14 ,  A61P31/16 ,  A61P35/00 ,  A61P37/02 ,  C07K14/11 ,  C12N7/00 ,  C12N7/01 ,  C12N7/04 ,  C12N15/09 ,  C12N15/86

CPC classification number: A61K39/145 ,  A61K39/0011 ,  A61K39/12 ,  A61K39/155 ,  A61K39/17 ,  A61K39/205 ,  A61K2039/525 ,  A61K2039/5254 ,  A61K2039/5256 ,  A61K2039/543 ,  A61K2039/552 ,  A61K2039/572 ,  A61K2039/585 ,  C07K14/005 ,  C12N7/00 ,  C12N15/86 ,  C12N2760/16121 ,  C12N2760/16122 ,  C12N2760/16132 ,  C12N2760/16134 ,  C12N2760/16143 ,  C12N2760/16151 ,  C12N2760/16161 ,  C12N2760/16162 ,  C12N2760/16171 ,  C12N2760/16221 ,  C12N2760/16222 ,  C12N2760/16232 ,  C12N2760/16234 ,  C12N2760/16243 ,  C12N2760/16251 ,  C12N2760/16262 ,  C12N2760/16271 ,  C12N2760/18022 ,  C12N2760/18034 ,  C12N2760/18122 ,  C12N2760/18134 ,  C12N2760/18522 ,  C12N2760/18534 ,  C12N2760/20222 ,  C12N2760/20234 ,  Y02A50/466

Abstract: The present invention relates, to novel methods and substrates for the propagation of viruses. The invention relates to IFN-deficient substrates and methods for propagating viruses in these unconventional substrates. In particular, the invention relates to methods of propagating viruses in immature embryonated eggs, preferably six- to nine-day-old chicken eggs. The methods of the invention are particularly attractive for growing viruses suitable for use in vaccine and pharmaceutical formulations.

Abstract translation: 本发明涉及用于病毒传播的新颖方法和底物。 本发明涉及在这些非传统基质中传播病毒的IFN-缺陷底物和方法。 特别地，本发明涉及在未成熟的含胚卵中，优选6至9天的鸡蛋中繁殖病毒的方法。 本发明的方法对于适用于疫苗和药物制剂的生长病毒特别有吸引力。

公开(公告)号：US20040109877A1

公开(公告)日：2004-06-10

申请号：US10713732

申请日：2003-11-14

Applicant: Mount Sinai School

Inventor： Peter Palese ,  Adolfo Garcia-Sastre ,  Thomas Muster

IPC: A61K039/12 ,  A61K039/145

CPC classification number: A61K39/145 ,  A61K39/0011 ,  A61K39/12 ,  A61K39/155 ,  A61K39/17 ,  A61K39/205 ,  A61K2039/525 ,  A61K2039/5254 ,  A61K2039/5256 ,  A61K2039/543 ,  A61K2039/552 ,  A61K2039/572 ,  A61K2039/585 ,  C07K14/005 ,  C12N7/00 ,  C12N15/86 ,  C12N2760/16121 ,  C12N2760/16122 ,  C12N2760/16132 ,  C12N2760/16134 ,  C12N2760/16143 ,  C12N2760/16151 ,  C12N2760/16161 ,  C12N2760/16162 ,  C12N2760/16171 ,  C12N2760/16221 ,  C12N2760/16222 ,  C12N2760/16232 ,  C12N2760/16234 ,  C12N2760/16243 ,  C12N2760/16251 ,  C12N2760/16262 ,  C12N2760/16271 ,  C12N2760/18022 ,  C12N2760/18034 ,  C12N2760/18122 ,  C12N2760/18134 ,  C12N2760/18522 ,  C12N2760/18534 ,  C12N2760/20222 ,  C12N2760/20234 ,  Y02A50/466

Abstract: The present invention relates, in general, to attenuated negative-strand RNA viruses having an impaired ability to antagonize the cellular interferon (IFN) response, and the use of such attenuated viruses in vaccine and pharmaceutical formulations. The invention also relates to the development and use of IFN-deficient systems for selection of such attenuated viruses. In particular, the invention relates to attenuated influenza viruses having modifications to the NS1 gene that diminish or eliminate the ability of the NS1 gene product to antagonize the cellular IFN response. The mutant viruses replicate in vivo but demonstrate reduced pathogenicity, and therefore are well suited for live virus vaccines, and pharmaceutical formulations.

Abstract translation: 本发明一般涉及具有拮抗细胞干扰素（IFN）应答能力受损的减毒负链RNA病毒，以及在疫苗和药物制剂中使用这种减毒病毒。 本发明还涉及用于选择这种减毒病毒的IFN-缺陷系统的开发和应用。 具体地，本发明涉及具有修饰的NS1基因的减毒流感病毒，其减少或消除NS1基因产物拮抗细胞IFN应答的能力。 突变体病毒在体内复制但表现出降低的致病性，因此非常适合于活病毒疫苗和药物制剂。

公开(公告)号：US06573079B1

公开(公告)日：2003-06-03

申请号：US09332286

申请日：1999-06-11

Applicant: Peter Palese ,  Adolfo García-Sastre ,  Robert O'Neil

Inventor： Peter Palese ,  Adolfo García-Sastre ,  Robert O'Neil

IPC: C12N700

CPC classification number: A61K39/145 ,  A61K39/0011 ,  A61K39/12 ,  A61K39/155 ,  A61K39/17 ,  A61K39/205 ,  A61K2039/525 ,  A61K2039/5254 ,  A61K2039/5256 ,  A61K2039/543 ,  A61K2039/552 ,  A61K2039/572 ,  A61K2039/585 ,  C07K14/005 ,  C12N7/00 ,  C12N15/86 ,  C12N2760/16121 ,  C12N2760/16122 ,  C12N2760/16132 ,  C12N2760/16134 ,  C12N2760/16143 ,  C12N2760/16151 ,  C12N2760/16161 ,  C12N2760/16162 ,  C12N2760/16171 ,  C12N2760/16221 ,  C12N2760/16222 ,  C12N2760/16232 ,  C12N2760/16234 ,  C12N2760/16243 ,  C12N2760/16251 ,  C12N2760/16262 ,  C12N2760/16271 ,  C12N2760/18022 ,  C12N2760/18034 ,  C12N2760/18122 ,  C12N2760/18134 ,  C12N2760/18522 ,  C12N2760/18534 ,  C12N2760/20222 ,  C12N2760/20234 ,  Y02A50/466

Abstract: The present invention relates, to novel methods and substrates for the propagation of viruses. The invention relates to IFN-deficient substrates and methods for propagating viruses in these unconventional substrates. In particular, the invention relates to methods of propagating viruses in immature embryonated eggs, preferably six- to nine-day-old chicken eggs. The methods of the invention are particularly attractive for growing viruses suitable for use in vaccine and pharmaceutical formulations.

公开(公告)号：US09352033B2

公开(公告)日：2016-05-31

申请号：US12364243

申请日：2009-02-02

Applicant: Peter Palese ,  Adolfo Garcia-Sastre ,  Robert E. O'Neil

Inventor： Peter Palese ,  Adolfo Garcia-Sastre ,  Robert E. O'Neil

IPC: C12N7/00 ,  A61K39/145 ,  C07K14/005 ,  C12N15/86 ,  A61K39/12 ,  A61K39/00

CPC classification number: A61K39/145 ,  A61K39/0011 ,  A61K39/12 ,  A61K39/155 ,  A61K39/17 ,  A61K39/205 ,  A61K2039/525 ,  A61K2039/5254 ,  A61K2039/5256 ,  A61K2039/543 ,  A61K2039/552 ,  A61K2039/572 ,  A61K2039/585 ,  C07K14/005 ,  C12N7/00 ,  C12N15/86 ,  C12N2760/16121 ,  C12N2760/16122 ,  C12N2760/16132 ,  C12N2760/16134 ,  C12N2760/16143 ,  C12N2760/16151 ,  C12N2760/16161 ,  C12N2760/16162 ,  C12N2760/16171 ,  C12N2760/16221 ,  C12N2760/16222 ,  C12N2760/16232 ,  C12N2760/16234 ,  C12N2760/16243 ,  C12N2760/16251 ,  C12N2760/16262 ,  C12N2760/16271 ,  C12N2760/18022 ,  C12N2760/18034 ,  C12N2760/18122 ,  C12N2760/18134 ,  C12N2760/18522 ,  C12N2760/18534 ,  C12N2760/20222 ,  C12N2760/20234 ,  Y02A50/466

Abstract: The present invention relates, to novel methods and substrates for the propagation of viruses. The invention relates to IFN-deficient substrates and methods for propagating viruses in these unconventional substrates. In particular, the invention relates to methods of propagating viruses in immature embryonated eggs, preferably six- to nine-day-old chicken eggs. The methods of the invention are particularly attractive for growing viruses suitable for use in vaccine and pharmaceutical formulations.

Abstract translation: 本发明涉及用于病毒传播的新颖方法和底物。 本发明涉及在这些非传统基质中传播病毒的IFN-缺陷底物和方法。 特别地，本发明涉及在未成熟的含胚卵中，优选6至9天的鸡蛋中繁殖病毒的方法。 本发明的方法对于适用于疫苗和药物制剂的生长病毒特别有吸引力。

公开(公告)号：US09187732B2

公开(公告)日：2015-11-17

申请号：US14049601

申请日：2013-10-09

Applicant: Baxter Healthcare SA

Inventor： Markus Wolschek ,  Andrej Egorov ,  Michael Bergmann ,  Thomas Muster ,  Christian Kittel

IPC: A61K39/00 ,  C07K14/005 ,  C12N7/00 ,  C12N15/86

CPC classification number: C12N7/00 ,  A61K39/00 ,  A61K2039/525 ,  A61K2039/5256 ,  C07K14/005 ,  C12N15/86 ,  C12N2760/16132 ,  C12N2760/16143 ,  C12N2760/16243

Abstract: The present invention relates to a novel replication deficient influenza virus comprising a modified NS1 segment coding for a NS1 protein lacking a functional RNA binding domain and functional effector domain and having a heterologous sequence inserted between the splice donor site and the splice acceptor site of the NS gene segment. The virus can be used as vector for expression of various proteins like chemokines, cytokines or antigenic structures and to produce vaccines. A fusion peptide comprising part of the N-terminus of an NS1 protein and a signal sequence fused to the C-terminus of said NS1 peptide is also provided.

Abstract translation: 本发明涉及一种新型的复制缺陷型流感病毒，其包含编码缺乏功能性RNA结合结构域和功能性效应子结构域的NS1蛋白质的修饰的NS1区段，并且在所述剪接供体位点和所述NS的剪接受体位点之间插入异源序列 基因片段。 该病毒可用作表达各种蛋白质（如趋化因子，细胞因子或抗原结构）并产生疫苗的载体。 还提供了包含NS1蛋白的N-末端的一部分和与所述NS1肽的C末端融合的信号序列的融合肽。

公开(公告)号：US20150166967A1

公开(公告)日：2015-06-18

申请号：US14528997

申请日：2014-10-30

Applicant: Wisconsin Alumni Research Foundation (WARF)

Inventor： Yoshihiro Kawaoka ,  Gabriele Neumann

IPC: C12N7/00

CPC classification number: C12N7/00 ,  A61K39/00 ,  A61K39/12 ,  A61K39/145 ,  A61K48/0091 ,  A61K2039/525 ,  A61K2039/5252 ,  A61K2039/5254 ,  A61K2039/5256 ,  C12N15/86 ,  C12N2760/16043 ,  C12N2760/16051 ,  C12N2760/16134 ,  C12N2760/16143 ,  C12N2760/16151 ,  C12N2760/16161 ,  C12N2760/16234 ,  C12N2760/16243 ,  C12N2760/16251 ,  C12N2760/16261 ,  Y02A50/412

Abstract: The invention provides a composition useful to prepare influenza viruses, e.g., in the absence of helper virus, using vectors which include tandem transcription cassettes containing PolI and/or PolII promoters.

Abstract translation: 本发明提供了可用于制备流感病毒的组合物，例如在不存在辅助病毒的情况下，使用包含含有PolI和/或PolII启动子的串联转录盒的载体。

公开(公告)号：US08877210B2

公开(公告)日：2014-11-04

申请号：US14156284

申请日：2014-01-15

Applicant: Medimmune, LLC

Inventor： Chin-Fen Yang ,  George Kemble ,  Chongguang Liu

IPC: A61K39/145 ,  C12N7/02 ,  C12Q1/70 ,  C07K14/005 ,  C12N9/24

CPC classification number: C07K14/005 ,  A61K39/00 ,  A61K39/12 ,  A61K39/145 ,  A61K2039/5254 ,  A61K2039/53 ,  C07H21/04 ,  C12N7/00 ,  C12N9/2402 ,  C12N15/86 ,  C12N2740/16122 ,  C12N2740/16222 ,  C12N2760/16122 ,  C12N2760/16134 ,  C12N2760/16143 ,  C12N2760/16161 ,  C12N2760/16222 ,  C12N2760/16234 ,  C12N2760/16243 ,  C12N2760/16261

Abstract: Polypeptides, polynucleotides, methods, compositions, and vaccines comprising influenza hemagglutinin and neuraminidase variants are provided.