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1. 发明申请

US20160361411A1 LIPID NANOPARTICLE VACCINE ADJUVANTS AND ANTIGEN DELIVERY SYSTEMS 审中-公开
公开(公告)号：US20160361411A1
公开(公告)日：2016-12-15
申请号：US15120954
申请日：2015-02-23
申请人： Marian Gindy , Danilo R. Casimiro , Andrew Bett , Jan H. Ter Meulen
发明人： Marian Gindy , Danilo R. Casimiro , Andrew Bett , Jan H. Ter Meulen
IPC分类号： A61K39/39 , A61K31/451 , A61K39/29 , A61K39/12 , C12N7/00 , A61K9/50 , A61K31/80
摘要： The instant invention provides for novel lipid nanoparticle (LNP) formulations, containing cationic lipids, for use as vaccine adjuvants and/or as antigen delivery systems. It is an object of the instant invention to provide LNP formulations that demonstrate enhancements in humoral and cellular immunogenicity of vaccine antigens, particularly subunit vaccine antigens, when utilized alone or in combination with immunostimulatory agents (e.g. small molecule or oligonucleotide TLR agonists). The instant invention further identifies physical and chemical properties of the LNP formulations that can be manipulated to enhance antigen efficiency and adjuvant tolerability in vivo.
摘要翻译：本发明提供了用作疫苗佐剂和/或作为抗原递送系统的新型脂质纳米颗粒（LNP）制剂，其含有阳离子脂质。本发明的目的是提供当单独使用或与免疫刺激剂（例如小分子或寡核苷酸TLR激动剂）组合使用时，证明疫苗抗原，特别是亚单位疫苗抗原的体液和细胞免疫原性增强的LNP制剂。本发明进一步鉴定LNP制剂的物理和化学性质，其可被操作以增强体内抗原效率和佐剂耐受性。

2. 发明申请

US20110008369A1 PD-1 BINDING PROTEINS 有权
标题翻译： PD-1结合蛋白
公开(公告)号：US20110008369A1
公开(公告)日：2011-01-13
申请号：US12922066
申请日：2009-03-03
申请人： Adam C. Finnefrock , Tong-Ming Fu , Daniel C. Freed , Danilo R. Casimiro , Fengsheng Li , Aimin Tang
发明人： Adam C. Finnefrock , Tong-Ming Fu , Daniel C. Freed , Danilo R. Casimiro , Fengsheng Li , Aimin Tang
IPC分类号： A61K39/395 , C07K16/18 , A61P37/04
CPC分类号： C07K16/2896 , C07K2317/24 , C07K2317/56 , C07K2317/565 , C07K2317/92 , C07K2319/30
摘要： The present invention features PD-1 binding proteins, a subset of which inhibits binding of PD-L1 to the PD-1 receptor. These binding proteins can be employed to modulate the immune system through the manipulation of the PD-1 signaling pathway, enhancing host immunity to treat infections and cancer.
摘要翻译：本发明的特征在于PD-1结合蛋白，其一部分抑制PD-L1与PD-1受体的结合。这些结合蛋白可用于通过操纵PD-1信号传导途径来调节免疫系统，增强宿主免疫治疗感染和癌症。

3. 发明授权

US06733993B2 Enhanced first generation adenovirus vaccines expressing codon optimized HIV1-gag, pol, nef and modifications 失效
标题翻译：增强的第一代腺病毒疫苗表达密码子优化的HIV1-gag，pol，nef和修饰
公开(公告)号：US06733993B2
公开(公告)日：2004-05-11
申请号：US09952060
申请日：2001-09-14
申请人： Emilio A. Emini , Rima Youil , Andrew J. Bett , Ling Chen , David C. Kaslow , John W. Shiver , Timothy J. Toner , Danilo R. Casimiro
发明人： Emilio A. Emini , Rima Youil , Andrew J. Bett , Ling Chen , David C. Kaslow , John W. Shiver , Timothy J. Toner , Danilo R. Casimiro
IPC分类号： C12P2106
CPC分类号： C12N7/00 , A61K2039/5256 , A61K2039/53 , A61K2039/545 , A61K2039/57 , C07K14/005 , C12N15/86 , C12N2710/10343 , C12N2710/10351 , C12N2740/16122 , C12N2740/16134 , C12N2740/16322 , C12N2740/16334 , C12N2830/42
摘要： First generation adenoviral vectors and associated recombinant adenovirus-based HIV vaccines which show enhanced stability and growth properties and greater cellular-mediated immunity are described within this specification. These adenoviral vectors are utilized to generate and produce through cell culture various adenoviral-based HIV-1 vaccines which contain HIV-1 gag, HIV-1 pol and/or HIV-1 nef polynucleotide pharmaceutical products, and biologically relevant modifications thereof. These adenovirus vaccines, when directly introduced into living vertebrate tissue, preferably a mammalian host such as a human or a non-human mammal of commercial or domestic veterinary importance, express the HIV1-Gag, Pol and/or Nef protein or biologically modification thereof, 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, encoding codon optimized HIV-1 Pol, derivatives of optimized HIV-1 Pol (including constructs wherein protease, reverse transcriptase, RNAse H and integrase activity of HIV-1 Pol is inactivated), HIV-1 Nef and derivatives of optimized HIV-1 Nef, including nef mutants which effect wild type characteristics of Nef, such as myristylation and down regulation of host CD4. The adenoviral vaccines of the present invention, when administered alone or in a combined modality regime, 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.
摘要翻译：在本说明书中描述了显示增强的稳定性和生长特性以及更大的细胞介导的免疫的第一代腺病毒载体和相关重组腺病毒的HIV疫苗。这些腺病毒载体用于通过细胞培养产生和产生各种含有HIV-1 gag，HIV-1 pol和/或HIV-1 nef多核苷酸药物产品的基于腺病毒的HIV-1疫苗及其生物相关的修饰。这些腺病毒疫苗当直接引入活的脊椎动物组织中时，优选哺乳动物宿主例如具有商业或家庭兽医重要性的人或非人哺乳动物，表达HIV1-Gag，Pol和/或Nef蛋白或其生物修饰，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的编码密码子优化的HIV-1 Pol的合成DNA分子，其优化的HIV-1 Pol的衍生物（包括其中蛋白酶，逆转录酶，RNAse H和HIV-1的整合酶活性 Pol被灭活），HIV-1 Nef和优化的HIV-1 Nef的衍生物，包括影响Nef野生型特征的nef突变体，如主体CD4的肉豆蔻酰化和下调。本发明的腺病毒疫苗当单独施用或以组合的方式给药时，将对先前未感染的个体提供预防优势，和/或通过减少被感染个体内的病毒载量水平提供治疗效果，从而延长无症状期 HIV-1感染。

4. 发明授权

US10449243B2 Dengue virus vaccine compositions and methods of use thereof 有权
公开(公告)号：US10449243B2
公开(公告)日：2019-10-22
申请号：US15536319
申请日：2015-12-18
申请人： Merck Sharp & Dohme Corp. , Danilo R. Casimiro , Andrew Bett , Beth-Ann Griswold Coller , Govindarajan Dhanasekaran , Ramesh V. Chintala
发明人： Danilo R. Casimiro , Andrew Bett , Beth-Ann Griswold Coller , Govindarajan Dhanasekaran , Ramesh V. Chintala
IPC分类号： A61K39/12 , C12N7/00 , A61K39/00
摘要： The present invention relates to dengue virus vaccine compositions comprising a first and a second dengue vaccine, wherein the first dengue vaccine comprises at least one live, 5 attenuated dengue virus or live, attenuated chimeric dengue virus and the second dengue vaccine is a recombinant dengue subunit vaccine, a DNA vaccine, a conjugate vaccine, or an inactivated dengue vaccine; wherein the genome of the live attenuated dengue virus or the live attenuated chimeric dengue virus comprises a 30 nucleotide deletion of the TL2 stem-loop structure of the 3′ untranslated region. The dengue virus vaccine compositions of the invention may further 10 comprise one or more adjuvants. In preferred embodiments of the invention, the first and the second dengue vaccine are tetravalent. The invention also relates to methods of using the dengue virus vaccine compositions of the invention to treat or prevent dengue infection, or to prevent, ameliorate, or delay the onset or progression of the clinical manifestations thereof.

5. 发明申请

US20110136896A1 VARIANT HCMV PP65, IE1, AND IE2 POLYNUCLEOTIDES AND USES THEREOF 审中-公开
标题翻译：各种HCMV PP65，IE1和IE2多核苷酸及其用途
公开(公告)号：US20110136896A1
公开(公告)日：2011-06-09
申请号：US13056899
申请日：2009-07-28
申请人： Tong-Ming Fu , Danilo R. Casimiro , Daniel C. Freed , Aimin Tang
发明人： Tong-Ming Fu , Danilo R. Casimiro , Daniel C. Freed , Aimin Tang
IPC分类号： A61K31/7088 , C07H21/04 , C07K14/005 , C12N15/63 , C12P21/06
CPC分类号： C07K14/005 , C12N2710/16122
摘要： The present invention relates to compositions and methods to elicit or enhance cell-mediated immunity against HCMV infection by providing polynucleotides encoding variant HCMV pp65, IE1, and IE2 proteins, and fusion proteins thereof. The present invention also provides recombinant vectors including, but not limited to, adenovirus and plasmid vectors comprising said polynucleotides and host cells comprising said recombinant vectors. Also provided herein are purified forms of the variant HCMV pp65, IE1, and IE2 proteins described herein, and fusion proteins. The variant HCMV proteins, and fusion proteins thereof, are useful as vaccines for the protection from and/or treatment of HCMV infection. Said vaccines are useful as a monotherapy or a part of a therapeutic regime, said regime comprising administration of a second vaccine such as a polynucleotide, cell-based, protein or peptide-based vaccine.
摘要翻译：本发明涉及通过提供编码变体HCMV pp65，IE1和IE2蛋白的多核苷酸及其融合蛋白来引发或增强细胞介导的HCMV感染免疫的组合物和方法。本发明还提供重组载体，包括但不限于腺病毒和包含所述多核苷酸的质粒载体和包含所述重组载体的宿主细胞。本文还提供了本文所述的变体HCMV pp65，IE1和IE2蛋白的纯化形式，以及融合蛋白。变体HCMV蛋白及其融合蛋白可用作用于保护和/或治疗HCMV感染的疫苗。所述疫苗可用作单一疗法或治疗方案的一部分，所述方案包括施用第二种疫苗，例如多核苷酸，基于细胞的，蛋白质或基于肽的疫苗。

6. 发明申请

US20100183651A1 Broadly Representative Antigen Sequences and Method for Selection 审中-公开
标题翻译：广泛代表性的抗原序列和选择方法
公开(公告)号：US20100183651A1
公开(公告)日：2010-07-22
申请号：US12593962
申请日：2008-03-26
申请人： Adam C. Finnefrock , Danilo R. Casimiro , Jon H. Condra , John W. Shiver , Andrew J. Bett
发明人： Adam C. Finnefrock , Danilo R. Casimiro , Jon H. Condra , John W. Shiver , Andrew J. Bett
IPC分类号： A61K39/21 , A61K39/00 , C12N7/01 , C12N5/00 , C12N15/63 , C07K7/06 , C07K7/08 , C07K14/005 , C07H21/04
CPC分类号： C07K14/005 , A61K39/00 , A61K39/12 , A61K39/21 , A61K2039/5256 , A61K2039/53 , A61K2039/54 , A61K2039/545 , A61K2039/57 , C07K16/1045 , C12N2710/10343 , C12N2740/16222 , C12N2740/16234 , C12N2740/16322 , C12N2740/16334 , G16B30/00
摘要： A novel method for generating vaccine sequences is disclosed herein that preserves contiguous epitope length stretches of amino acids or nucleotides from an input pool of sequences. The method generates continuous, stepwise epitope consensus that together provides for a single globally optimized sequence. The end sequences are designed to maximize overlap between any potential epitope length sequence extract from a natural antigen sequence. The disclosed method, thus, allows one to maximize the number of potential natural epitopes that are mimicked in a resultant vaccine sequence. Various representative HIV vaccine sequences have been generated and are disclosed herein.
摘要翻译：本文公开了一种用于产生疫苗序列的新方法，其从输入的序列库中保留氨基酸或核苷酸的连续表位长度的延伸。该方法产生连续的逐步表位一致性，共同提供单个全局优化的序列。设计末端序列以使来自天然抗原序列的任何潜在表位长度序列提取物之间的重叠最大化。因此，所公开的方法允许最大化在所得疫苗序列中模拟的潜在天然表位的数量。已经产生了各种代表性的HIV疫苗序列，并在此公开。

7. 发明申请

US20080254059A1 Adenovirus Serotype 26 Vectors, Nucleic Acid and Viruses Produced Thereby 审中-公开
标题翻译：腺病毒血清型26载体，核酸和由此产生的病毒
公开(公告)号：US20080254059A1
公开(公告)日：2008-10-16
申请号：US11884086
申请日：2006-02-07
申请人： Andrew J. Bett , Danilo R. Casimiro , John W. Shiver , Emilio A. Emini , Michael Chastain , David C. Kaslow
发明人： Andrew J. Bett , Danilo R. Casimiro , John W. Shiver , Emilio A. Emini , Michael Chastain , David C. Kaslow
IPC分类号： A61K39/00 , C12N15/00 , C12N5/06 , C12N15/87 , A61P37/00 , C12N7/00 , A61K35/76 , A61K31/70
CPC分类号： C12N15/86 , A61K39/12 , A61K39/21 , A61K2039/5256 , A61K2039/54 , A61K2039/545 , A61K2039/57 , C07K14/005 , C12N7/00 , C12N2710/10321 , C12N2710/10343 , C12N2740/16134 , C12N2740/16234 , C12N2740/16334
摘要： Adenoviral serotypes differ in their natural tropism. The various serotypes of adenovirus have been found to differ in at least their capsid proteins (e.g., penton-base and hexon proteins), proteins responsible for cell binding (e.g., fiber proteins), and proteins involved in adenovirus replication. This difference in tropism and capsid proteins among serotypes has led to many research efforts aimed at redirecting the adenovirus tropism by modification of the capsid proteins. The present invention bypasses such requirement for capsid protein modification as it presents a recombinant, replication-defective adenovirus of serotype 26, a rare adenoviral serotype, and methods for generating the alternative, recombinant adenovirus. Additionally, means of employing the recombinant adenovirus for delivery and expression of heterologous genes are provided.
摘要翻译：腺病毒血清型的自然向性不同。已经发现各种各样的腺病毒血清型在至少它们的衣壳蛋白（例如，五邻体和六邻体蛋白），负责细胞结合的蛋白质（例如纤维蛋白）和参与腺病毒复制的蛋白质中不同。血清型中的向性和衣壳蛋白的这种差异导致了许多研究工作，旨在通过修饰衣壳蛋白来重新定向腺病毒向性。本发明绕过这样的衣壳蛋白修饰的要求，因为它呈现血清型26的重组复制缺陷型腺病毒，罕见的腺病毒血清型，以及产生替代重组腺病毒的方法。另外，提供了使用重组腺病毒递送和表达异源基因的方法。

8. 发明授权

US06787351B2 Adenovirus carrying gag gene HIV vaccine 失效
标题翻译：携带gag基因HIV疫苗的腺病毒
公开(公告)号：US06787351B2
公开(公告)日：2004-09-07
申请号：US09818443
申请日：2001-03-27
申请人： Ling Chen , John W. Shiver , Andrew J. Bett , Danilo R. Casimiro , Michael J. Caulfield , Michael A. Chastain , Emilio A. Emini
发明人： Ling Chen , John W. Shiver , Andrew J. Bett , Danilo R. Casimiro , Michael J. Caulfield , Michael A. Chastain , Emilio A. Emini
IPC分类号： C12N1574
CPC分类号： C12N15/86 , A61K2039/5256 , A61K2039/53 , C07K14/005 , C12N2710/10343 , C12N2740/16122 , C12N2740/16134 , C12Q1/703
摘要： An adenoviral vector is described which carries a codon-optimized gag gene, along with a heterologous promoter and transcription terminator. This viral vaccine can effectively prevent HIV infection when administered to humans either alone or as part of a prime and boost regime also with a vaccine plasmid.
摘要翻译：描述了携带密码子优化的gag基因以及异源启动子和转录终止子的腺病毒载体。当病毒疫苗单独使用或作为初始和加强方案的一部分也可用疫苗质粒时，可有效预防HIV感染。

9. 发明申请

US20170360917A1 DENGUE VIRUS VACCINE COMPOSITIONS AND METHODS OF USE THEREOF 审中-公开
公开(公告)号：US20170360917A1
公开(公告)日：2017-12-21
申请号：US15536319
申请日：2015-12-18
申请人： Danilo R. CASIMIRO , Andrew BETT , Beth-Ann Griswold COLLER , Govindarajan DHANASEKARAN , Ramesh V. CHINTALA , Merck Sharp & Dohme Corp.
发明人： Danilo R. Casimiro , Andrew Bett , Beth-Ann Griswold Coller , Govindarajan Dhanasekaran , Ramesh V. Chintala
IPC分类号： A61K39/12 , C12N7/00 , A61K39/00
CPC分类号： A61K39/12 , A61K2039/5252 , A61K2039/5254 , A61K2039/545 , A61K2039/55505 , A61K2039/55577 , A61K2039/575 , A61K2039/70 , C12N7/00 , C12N2770/24122 , C12N2770/24134 , C12N2770/24171 , Y02A50/386
摘要： The present invention relates to dengue virus vaccine compositions comprising a first and a second dengue vaccine, wherein the first dengue vaccine comprises at least one live, 5 attenuated dengue virus or live, attenuated chimeric dengue virus and the second dengue vaccine is a recombinant dengue subunit vaccine, a DNA vaccine, a conjugate vaccine, or an inactivated dengue vaccine; wherein the genome of the live attenuated dengue virus or the live attenuated chimeric dengue virus comprises a 30 nucleotide deletion of the TL2 stem-loop structure of the 3′ untranslated region. The dengue virus vaccine compositions of the invention may further 10 comprise one or more adjuvants. In preferred embodiments of the invention, the first and the second dengue vaccine are tetravalent. The invention also relates to methods of using the dengue virus vaccine compositions of the invention to treat or prevent dengue infection, or to prevent, ameliorate, or delay the onset or progression of the clinical manifestations thereof.

10. 发明申请

US20120121630A1 RECOMBINANT ECTODOMAIN EXPRESSION OF HERPES SIMPLEX VIRUS GLYCOPROTEINS IN YEAST 审中-公开
标题翻译： HERPES的重组ECTODOMAIN表达简单病毒糖蛋白在YEAST
公开(公告)号：US20120121630A1
公开(公告)日：2012-05-17
申请号：US13386508
申请日：2010-07-21
申请人： Janine T. Bryan , John W. Ballet , Jessica A. Flynn , Danilo R. Casimiro , Robert C. Davidson , Victoria Copeland , Sandra E. Rios , Byung-Kwon Choi , Stefan Wildt
发明人： Janine T. Bryan , John W. Ballet , Jessica A. Flynn , Danilo R. Casimiro , Robert C. Davidson , Victoria Copeland , Sandra E. Rios , Byung-Kwon Choi , Stefan Wildt
IPC分类号： A61K39/245 , A61P37/06 , C12N15/38 , C07K14/035 , C12P21/00
CPC分类号： A61K39/245 , A61K39/12 , A61K2039/55505 , A61K2039/55577 , A61K2039/57 , C12N2710/16622 , C12N2710/16634
摘要： The present invention provides Herpes Simplex Virus (HSV) gD, gC, gB and/or gE recombinant glycoproteins having a particular pre-selected N-linked glycosylation pattern as the predominant N-glycoform. The present invention also provides methods of producing these recombinant glycoproteins in yeast, preferably Pichia pastoris, which may be glycoengineered to provide particular glycosylation patterns. The present invention further provides vaccines comprising gD and gC, and optionally gB and/or gE, at least one of which has a particular pre-selected N-linked glycosylation pattern as the predominant N-glycoform. The recombinant glycoproteins are produced by a method which, in one embodiment, comprises transforming a yeast of the genus Pichia with an expression vector containing a DNA encoding an HSV glycoprotein, which is under regulation of a promoter functional in a yeast of the genus Pichia, culturing the yeast in a medium, and recovering the recombinant glycoprotein from the obtained culture. DNA encoding the recombinant glycoproteins is preferably codon-optimized to achieve optimal expression in Pichia.
摘要翻译：本发明提供具有特定预先选择的N-连接的糖基化模式作为主要N-糖型的单纯疱疹病毒（HSV）gD，gC，gB和/或gE重组糖蛋白。本发明还提供了在酵母，优选巴斯德毕赤酵母中生产这些重组糖蛋白的方法，其可以进行糖工程以提供特定的糖基化模式。本发明还提供了包含gD和gC以及任选的gB和/或gE的疫苗，其中至少一种具有特定的预先选择的N-连接的糖基化模式作为主要的N-糖基型。重组糖蛋白通过一种方法产生，在一个实施方案中，该方法包括用含有编码HSV糖蛋白的DNA的表达载体转化毕赤酵母属的酵母，所述HSV糖蛋白在毕赤酵母属酵母中起促进作用的启动子的调控，在培养基中培养酵母，并从获得的培养物中回收重组糖蛋白。编码重组糖蛋白的DNA优选密码子优化以在毕赤酵母中达到最佳表达。

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