公开(公告)号：US20150307850A1

公开(公告)日：2015-10-29

申请号：US14649669

申请日：2013-12-04

Applicant: Tong-ming FU ,  Dai WANG ,  Danilo CASIMIRO ,  Daniel FREED ,  Fengsheng LI ,  MERCK SHARP & DOHME CORP.

Inventor： Tong-Ming Fu ,  Dai Wang ,  Danilo Casimiro ,  Daniel C. Freed ,  Fengsheng Li

IPC: C12N7/00 ,  A61K39/245 ,  C07K14/005

CPC classification number: C12N7/00 ,  A61K39/12 ,  A61K39/21 ,  A61K39/245 ,  A61K2039/5256 ,  C07K14/005 ,  C12N15/86 ,  C12N2710/16121 ,  C12N2710/16122 ,  C12N2710/16134 ,  C12N2710/16141 ,  C12N2710/16152 ,  C12N2710/16162 ,  C12N2740/16234

Abstract: The present invention relates to a cytomegalovirus (CMV) which has been recombinantly altered to express a heterologous polypeptide and to allow for external control of viral replication. The heterologous polypeptide may be a polypeptide of interest such as an antigen, antibody or immune modulator. The CMV vectors of the invention are replication defective, or chemically controllable replication capable, or replication competent. The present invention also relates to uses of the CMV vectors such as inducing an immune response to an antigen or expressing an antibody or immune modulator in vivo. Compositions comprising the CMV expressing the heterologous polypeptide are also encompassed by the present invention.

Abstract translation: 本发明涉及重组改变以​​表达异源多肽并允许外部控制病毒复制的巨细胞病毒（CMV）。 异源多肽可以是感兴趣的多肽，例如抗原，抗体或免疫调节剂。 本发明的CMV载体是复制缺陷的，或具有化学上可控的复制能力或复制能力的。 本发明还涉及CMV载体的用途，例如在体内诱导对抗原的免疫应答或表达抗体或免疫调节剂。 包含表达异源多肽的CMV的组合物也包括在本发明中。

公开(公告)号：US07709010B2

公开(公告)日：2010-05-04

申请号：US12074783

申请日：2008-03-06

Applicant: Janine T. Bryan ,  Michelle K. Brownlow ,  Li Shi ,  Danilo Casimiro ,  William L. McClements ,  Brian K. Meyer ,  Binghua Hu

Inventor： Janine T. Bryan ,  Michelle K. Brownlow ,  Li Shi ,  Danilo Casimiro ,  William L. McClements ,  Brian K. Meyer ,  Binghua Hu

IPC: A61K45/00

CPC classification number: A61K39/12 ,  A61K2039/5258 ,  A61K2039/55505 ,  A61K2039/55577 ,  A61K2039/70 ,  C12N7/00 ,  C12N2710/20023 ,  C12N2710/20034

Abstract: The present invention relates to pharmaceutical compositions comprising virus-like particles (VLPs) of HPV, said VLPs adsorbed to an aluminum adjuvant, and an ISCOM-type adjuvant comprising a saponin, cholesterol, and a phospholipid. In preferred embodiments, the aluminum adjuvant comprises amorphous aluminum hydroxyphosphate sulfate. Another aspect of the invention provides multi-dose HPV vaccine formulations comprising HPV VLPs and an antimicrobial preservative selected from the group consisting of: m-cresol, phenol and benzyl alcohol. Also provided are methods of using the disclosed pharmaceutical compositions and formulations to induce an immune response against HPV in a human patient and to prevent HPV infection.

Abstract translation: 本发明涉及包含HPV病毒样颗粒（VLP），所述VLP吸附于铝佐剂的IS​​MA型佐剂和包含皂角苷，胆固醇和磷脂的ISCOM型佐剂的药物组合物。 在优选的实施方案中，铝佐剂包括无定形的羟基磷酸氢铝硫酸盐。 本发明的另一方面提供了包含HPV VLP和选自间甲酚，苯酚和苄醇的抗微生物防腐剂的多剂量HPV疫苗制剂。 还提供了使用所公开的药物组合物和制剂在人类患者中诱导针对HPV的免疫应答并防止HPV感染的方法。

公开(公告)号：US20070077257A1

公开(公告)日：2007-04-05

申请号：US11604553

申请日：2006-11-27

Applicant: Emilio Emini ,  Rima Youil ,  Andrew Bett ,  Ling Chen ,  David Kaslow ,  John Shiver ,  Timothy Toner ,  Danilo Casimiro

Inventor： Emilio Emini ,  Rima Youil ,  Andrew Bett ,  Ling Chen ,  David Kaslow ,  John Shiver ,  Timothy Toner ,  Danilo Casimiro

IPC: A61K39/00 ,  A61K39/12

CPC classification number: A61K39/21 ,  A61K39/12 ,  A61K2039/5256 ,  A61K2039/53 ,  A61K2039/545 ,  A61K2039/55555 ,  C07K14/005 ,  C12N7/00 ,  C12N2710/10343 ,  C12N2710/10351 ,  C12N2740/16222 ,  C12N2740/16234 ,  C12N2740/16322 ,  C12N2740/16334

Abstract: First generation adenoviral vectors and-recombinant adenovirus-based HIV vaccines which contain HIV-1 gag, HIV-1 pol and/or HIV-1 nef polynucleotide pharmaceutical products, and biologically relevant modifications thereof are described. The adenovirus vaccines, when directly introduced into living vertebrate tissue, express the relevant proteins, inducing a cellular immune response which specifically recognizes HIV-1. The exemplified polynucleotides of the present invention are synthetic DNA molecules encoding HIV-1 Gag, HIV-1 Pol, HIV-1 Nef, and derivatives thereof. The adenoviral vaccines of the present invention, alone or in combination, will offer a prophylactic advantage to previously uninfected individuals and/or provide a therapeutic effect by reducing viral load levels within an infected individual, thus prolonging the asymptomatic phase of HIV-1 infection.

Abstract translation: 描述了含有HIV-1 gag，HIV-1 pol和/或HIV-1 nef多核苷酸药物产品的第一代腺病毒载体和基于重组腺病毒的HIV疫苗及其生物学相关的修饰。 当直接引入活的脊椎动物组织中时，腺病毒疫苗表达相关蛋白质，诱导特异性识别HIV-1的细胞免疫应答。 本发明的示例性多核苷酸是编码HIV-1Gag，HIV-1 Pol，HIV-1 Nef的合成DNA分子及其衍生物。 本发明的单独或组合的腺病毒疫苗将对先前未感染的个体提供预防优势，和/或通过减少感染个体内的病毒载量水平提供治疗效果，从而延长HIV-1感染的无症状期。

公开(公告)号：US20060148750A1

公开(公告)日：2006-07-06

申请号：US11345127

申请日：2006-02-01

Applicant: John Shiver ,  Helen Perry ,  Danilo Casimiro ,  Tong-Ming Fu

Inventor： John Shiver ,  Helen Perry ,  Danilo Casimiro ,  Tong-Ming Fu

IPC: A61K48/00

CPC classification number: C07K14/005 ,  A61K2039/53 ,  C07H21/02 ,  C12N2740/16222 ,  C12N2740/16234 ,  C12N2800/22

Abstract: Pharmaceutical compositions which comprise HIV Pol DNA vaccines are disclosed, along with the production and use of these DNA vaccines. The pol-based DNA vaccines of the invention are administered directly introduced into living vertebrate tissue, preferably humans, and preferably express inactivated versions of the HIV Pol protein devoid of protease, reverse transcriptase activity, RNase H activity and integrase activity, inducing a cellular immune response which specifically recognizes human immunodeficiency virus-1 (HIV-1). The DNA molecules which comprise the open reading frame of these DNA vaccines are synthetic DNA molecules encoding codon optimized HIV-1 Pol and codon optimized inactive derivatives of optimized HIV-1 Pol, including DNA molecules which encode inactive Pol proteins which comprise an amino terminal leader peptide.

Abstract translation: 公开了包含HIV Pol DNA疫苗的药物组合物以及这些DNA疫苗的生产和使用。 将本发明的基于pol的DNA疫苗直接施用于活的脊椎动物组织，优选人，并且优选表达不含蛋白酶的HIV Pol蛋白，逆转录酶活性，RNase H活性和整合酶活性的失活形式，诱导细胞免疫 具体承认人体免疫缺陷病毒-1（HIV-1）的反应。 构成这些DNA疫苗的开放阅读框架的DNA分子是编码经优化的HIV-1 Pol的密码子优化的HIV-1 Pol和密码子优化的非活性衍生物的合成DNA分子，其包括编码无效Pol蛋白的DNA分子，其包含氨基末端引物 肽。