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1. 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。

2. 发明授权

US08168757B2 PD-1 binding proteins 有权
标题翻译： PD-1结合蛋白
公开(公告)号：US08168757B2
公开(公告)日：2012-05-01
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： C07K16/00
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。

4. 发明申请

US20050215508A1 Polynucleotide vaccines expressing codon optimized HIV-1 Nef and modified HIV-1 Nef 审中-公开
标题翻译：表达密码子优化的HIV-1 Nef和修饰的HIV-1 Nef的多核苷酸疫苗
公开(公告)号：US20050215508A1
公开(公告)日：2005-09-29
申请号：US11081244
申请日：2005-03-16
申请人： John Shiver , Xiaoping Liang , Tong-Ming Fu
发明人： John Shiver , Xiaoping Liang , Tong-Ming Fu
IPC分类号： A61K48/00 , C07K14/16
CPC分类号： C07K14/005 , A61K2039/53 , C12N2740/16322
摘要： Pharmaceutical compositions which comprise HIV Nef DNA vaccines are disclosed, along with the production and use of these DNA vaccines. The nef-based DNA vaccines of the invention are administered directly introduced into living vertebrate tissue, preferably humans, and express the HIV Nef protein or biologically relevant portions thereof, 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 Nef and derivatives of optimized HIV-1 Nef, including nef modifications comprising amino terminal leader peptides, removal of the amino terminal myristylation site, and/or modification of the Nef dileucine motif. These modifications may effect wild type characteristics of Nef, such as myristylation and down regulation of host CD4.
摘要翻译：公开了包含HIV Nef 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nef的DNA疫苗直接施用于活的脊椎动物组织，优选人，并且表达HIV Nef蛋白或其生物相关部分，诱导特异性识别人免疫缺陷病毒-1（HIV-1 ）。构成这些DNA疫苗的开放阅读框架的DNA分子是编码密码子优化的HIV-1 Nef和优化的HIV-1 Nef的衍生物的合成DNA分子，包括包含氨基末端前导肽的nef修饰，氨基末端的肉豆蔻酰化位点的去除，和/或Nef二氨基酸基序的修饰。这些修饰可能会影响Nef的野生型特征，如主要病毒的肉豆蔻酰化和下调。

5. 发明申请

US20160130327A1 CMV NEUTRALIZING ANTIGEN BINDING PROTEINS 有权
标题翻译： CMV中和抗原结合蛋白
公开(公告)号：US20160130327A1
公开(公告)日：2016-05-12
申请号：US14897374
申请日：2014-06-09
申请人： Tong-Ming FU , Dai WANG , Zhiqiang AN
发明人： Tong-Ming Fu , Dai Wang , Zhiqiang An
IPC分类号： C07K16/08
CPC分类号： C07K16/088 , C07K2317/24 , C07K2317/565 , C07K2317/734 , C07K2317/76 , C07K2317/92 , C12Q1/70
摘要： The present invention is directed to antigen binding proteins including, but not limited to, monoclonal antibodies and antigen binding fragments thereof, that specifically bind to and preferably neutralize human cytomegalovirus (CMV). Also encompassed by the invention are antigen binding proteins that have been humanized. The antigen binding proteins of the invention are useful as a therapeutic agent for treating and/or preventing CMV infections in a patient in need thereof.
摘要翻译：本发明涉及特异性结合并优选中和人巨细胞病毒（CMV）的抗原结合蛋白，包括但不限于单克隆抗体及其抗原结合片段。本发明还包括已经人源化的抗原结合蛋白。本发明的抗原结合蛋白可用作治疗和/或预防有需要的患者的CMV感染的治疗剂。

6. 发明申请

US20150307850A1 CONDITIONAL REPLICATING VIRAL VECTORS 审中-公开
标题翻译：条件替代的VIRAL VECTORS
公开(公告)号：US20150307850A1
公开(公告)日：2015-10-29
申请号：US14649669
申请日：2013-12-04
申请人： Tong-ming FU , Dai WANG , Danilo CASIMIRO , Daniel FREED , Fengsheng LI , MERCK SHARP & DOHME CORP.
发明人： Tong-Ming Fu , Dai Wang , Danilo Casimiro , Daniel C. Freed , Fengsheng Li
IPC分类号： C12N7/00 , A61K39/245 , C07K14/005
CPC分类号： 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
摘要： 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.
摘要翻译：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。

7. 发明申请

US20060148750A1 Polynucleotide vaccines expressing codon optimized HIV-1 Pol and modified HIV-1 Pol 审中-公开
标题翻译：表达密码子优化的HIV-1 Pol和修饰的HIV-1 Pol的多核苷酸疫苗
公开(公告)号：US20060148750A1
公开(公告)日：2006-07-06
申请号：US11345127
申请日：2006-02-01
申请人： John Shiver , Helen Perry , Danilo Casimiro , Tong-Ming Fu
发明人： John Shiver , Helen Perry , Danilo Casimiro , Tong-Ming Fu
IPC分类号： A61K48/00
CPC分类号： C07K14/005 , A61K2039/53 , C07H21/02 , C12N2740/16222 , C12N2740/16234 , C12N2800/22
摘要： 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.
摘要翻译：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。

8. 发明授权

US09546355B2 Conditional replicating cytomegalovirus as a vaccine for CMV 有权
标题翻译：条件复制巨细胞病毒作为CMV疫苗
公开(公告)号：US09546355B2
公开(公告)日：2017-01-17
申请号：US14343637
申请日：2012-09-04
申请人： Tong-Ming Fu , Dai Wang , Muneeswara Babu Medi
发明人： Tong-Ming Fu , Dai Wang , Muneeswara Babu Medi
IPC分类号： C12N7/00 , A61K39/12 , A61K39/00
CPC分类号： C12N7/00 , A61K39/12 , A61K2039/5252 , A61K2039/5254 , A61K2039/55505 , A61K2039/55577 , C12N2710/16134
摘要： The present invention relates to methods of inducing an immune response to cytomegalovirus (CMV) using a genetically modified CMV that is conditionally replication defective. The methods of the invention can be used to treat and/or prevent primary CMV infection, infection due to reactivation of a latent CMV and a super-infection of a different strain of CMV that had been previously encountered. The present invention also relates to a replication defective CMV which has been recombinantly altered to allow for external control of viral replication. Compositions comprising the replication defective CMV are also encompassed by the present invention.
摘要翻译：本发明涉及使用有条件复制缺陷的遗传修饰的CMV诱导对巨细胞病毒（CMV）的免疫应答的方法。本发明的方法可用于治疗和/或预防原发性CMV感染，由于潜在CMV的再活化引起的感染和先前已经遇到的不同CMV株的超感染。本发明还涉及重组改变以允许外部控制病毒复制的复制缺陷型CMV。包含复制缺陷型CMV的组合物也包括在本发明中。

9. 发明申请

US20050106123A1 Method of inducing an enhanced immune response against hiv 审中-公开
标题翻译：诱导针对HIV的增强的免疫应答的方法
公开(公告)号：US20050106123A1
公开(公告)日：2005-05-19
申请号：US10507098
申请日：2003-03-12
申请人： Emilio Emini , John Shiver , Michael Chastain , Danilo Casimiro , Tong-Ming Fu , Xiaoping Liang
发明人： Emilio Emini , John Shiver , Michael Chastain , Danilo Casimiro , Tong-Ming Fu , Xiaoping Liang
IPC分类号： A61K39/00 , A61K39/21 , C07K14/16 , C12N15/861 , C12N15/863 , A61K48/00 , A61K39/12 , C12N15/867
CPC分类号： C12N15/86 , A61K39/12 , A61K39/21 , A61K2039/5256 , A61K2039/545 , C07K14/005 , C12N2710/10343 , C12N2710/24043 , C12N2710/24143 , C12N2740/15034 , C12N2740/16122 , C12N2740/16134 , C12N2740/16234 , C12N2830/42
摘要： An efficient means of inducing an immune response against human immunodeficiency virus (“HIV”) utilizing specific prime-boost regimes is disclosed. The specific prime-boost regimes employ a heterologous prime-boost protocol wherein recombinant adenoviral and poxvirus vectors comprising exogenous genetic material encoding a common HIV antigen are administered in that order. Vaccines administered into living vertebrate tissue in accordance with the disclosed regimes, preferably a mammalian host such as a human or a non-human mammal of commercial or domestic veterinary importance, express the HIV-1 antigen (e.g., Gag), inducing a cellular immune response which specifically recognizes HIV-1. It is believed that the disclosed prime/boost 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：公开了一种利用特定初始 - 加强方式诱导针对人类免疫缺陷病毒（“HIV”）的免疫应答的有效手段。特异性初始 - 加强方案采用异源初始 - 加强方案，其中包含编码常见HIV抗原的外源遗传物质的重组腺病毒和痘病毒载体以该顺序施用。根据所公开的方案，优选哺乳动物宿主例如商业或家庭兽医重要的人或非人哺乳动物施用于活的脊椎动物组织的疫苗表达HIV-1抗原（例如，Gag），诱导细胞免疫专门承认艾滋病毒1的反应。相信所公开的主要/加强方案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。

10. 发明授权

US06653125B2 Synthetic hepatitis C genes 失效
标题翻译：合成丙型肝炎基因
公开(公告)号：US06653125B2
公开(公告)日：2003-11-25
申请号：US09194949
申请日：2000-02-17
申请人： John J. Donnelly , Margaret A. Liu , John W. Shiver , Tong-Ming Fu
发明人： John J. Donnelly , Margaret A. Liu , John W. Shiver , Tong-Ming Fu
IPC分类号： C12N1579
CPC分类号： C07K14/005 , A61K39/00 , A61K48/00 , A61K2039/53 , C12N2770/24222
摘要： The present invention relates to polynucleotides comprising a DNA sequence encoding an HCV protein and fragments thereof that contain codons optimized for expression in a vertebrate host. Uses of the polynucleotides include eliciting an immune response specifically recognizing HCV.
摘要翻译：本发明涉及包含编码HCV蛋白的DNA序列的多核苷酸及其片段，其含有在脊椎动物宿主中表达的优化的密码子。多核苷酸的用途包括引发特异性识别HCV的免疫应答。

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