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1. 发明申请

WO2011144358A1 HISTIDINE-CONTAINING SOLUTION FOR TRANSFECTION AND/OR INJECTION OF NUCLEIC ACIDS AND USES THEREOF 审中-公开
标题翻译：用于转运和/或注射核酸的含HISTIDINE的解决方案及其用途
公开(公告)号：WO2011144358A1
公开(公告)日：2011-11-24
申请号：PCT/EP2011/002538
申请日：2011-05-20
申请人： CUREVAC GMBH , GORLOVOY, Philipp , SCHLAKE, Thomas , BAUMHOF, Patrick
发明人： GORLOVOY, Philipp , SCHLAKE, Thomas , BAUMHOF, Patrick
IPC分类号： A61K31/4172 , A61K47/18 , A61K48/00
CPC分类号： C12N15/87 , A61K9/0019 , A61K31/4172 , A61K47/183 , A61K47/543 , A61K47/58 , A61K47/59 , A61K47/593 , A61K47/595 , A61K48/00 , A61K48/0008 , A61K2039/53
摘要： The present invention is directed to a solution for transfection and/or injection containing at least one nucleic acid (sequence) and (free) histidine in a concentration of about 1 to about 25 μΜ. The present invention is also directed to the use of such histidine-containing solutions for transfection and/or injection of nucleic acid(s) (sequences), in particular for improvement of the transfection efficiency and/or endosomal release of nucleic acids. It is also directed to pharmaceutical compositions comprising such an inventive solution and its use as a medicament and/or for the prophylaxis, the treatment and/or the amelioration of various diseases as mentioned herein, e.g. by vaccination. The present invention is also directed to a method for transfection of a cell or an organism utilizing these inventive solutions and pharmaceutical compositions and to kits, comprising the inventive solution or pharmaceutical compositions thereof.
摘要翻译：本发明涉及含有浓度为约1至约25μΩ的至少一种核酸（序列）和（游离）组氨酸的转染和/或注射溶液。本发明还涉及这种含有组氨酸的溶液用于转染和/或注射核酸（序列）的用途，特别是用于改善核酸的转染效率和/或内体内释放。还涉及包含这样的本发明溶液及其作为药物的用途和/或用于预防，治疗和/或改善本文所述的各种疾病的药物组合物，例如，通过疫苗接种。本发明还涉及一种利用这些本发明溶液和药物组合物以及包含本发明溶液或其药物组合物的试剂盒转染细胞或生物体的方法。

2. 发明申请

WO2009030481A1 COMPLEXES OF RNA AND CATIONIC PEPTIDES FOR TRANSFECTION AND FOR IMMUNOSTIMULATION 审中-公开
标题翻译： RNA和阳离子肽的复制用于转移和免疫
公开(公告)号：WO2009030481A1
公开(公告)日：2009-03-12
申请号：PCT/EP2008/007244
申请日：2008-09-04
申请人： CUREVAC GMBH , FOTIN-MLECZEK, Mariola , BAUMHOF, Patrick
发明人： FOTIN-MLECZEK, Mariola , BAUMHOF, Patrick
IPC分类号： C12N15/87 , A61K48/00 , A61K47/34 , A61K47/48
CPC分类号： A61K48/005 , A61K9/0019 , A61K38/45 , A61K38/4846 , A61K39/00 , A61K47/61 , A61K47/6455 , A61K48/0033 , A61K48/0041 , A61K48/0066 , A61K48/0075 , A61K2039/53 , C07K19/00 , C12N9/0069 , C12N15/87 , C12Y113/12007 , C12Y204/01007 , C12Y304/21022
摘要： The present invention relates to a complexed RNA, comprising at least one RNA complexed with one or more oligopeptides, wherein the oligopeptide, which has the function of cell-penetrating peptide (CPP), has a length of 8 to 15 amino acids and has the empirical formula (Arg) ι ;(;Lys) m ;(His) n ;(Om) o ;(Xaa) x with the majority of residues being selected from Arg, Lys, His, Om. The invention further relates to a method for transfecting a cell or an organism, thereby applying the inventive complexed RNA. Additionally, pharmaceutical compositions and kits comprising the inventive complexed RNA, as well as the use of the inventive complexed RNA for transfecting a cell, tissue or an organism and/or for modulating, preferably inducing or enhancing, an immune response are disclosed herein.
摘要翻译：本发明涉及复合RNA，其包含与一种或多种寡肽复合的至少一种RNA，其中具有细胞穿透肽（CPP）功能的寡肽具有8至15个氨基酸的长度，并且具有经验式（Arg）2;（; Lys）m;（His）n;（Om）o;（Xaa）x，大部分残基选自Arg，Lys，His，Om。本发明还涉及用于转染细胞或生物体的方法，从而应用本发明的复合RNA。此外，本文公开了包含本发明复合RNA的药物组合物和试剂盒，以及本发明的复合RNA用于转染细胞，组织或生物体和/或用于调节，优选诱导或增强免疫应答的用途。

3. 发明申请

WO2013174409A1 REVERSIBLE IMMOBILIZATION AND/OR CONTROLLED RELEASE OF NUCLEIC ACID CONTAINING NANOPARTICLES BY (BIODEGRADABLE) POLYMER COATINGS 审中-公开
标题翻译：（可生物降解）聚合物涂层可逆稳定和/或控制含有纳米粒子的核酸的释放
公开(公告)号：WO2013174409A1
公开(公告)日：2013-11-28
申请号：PCT/EP2012/002257
申请日：2012-05-25
申请人： CUREVAC GMBH , BAUMHOF, Patrick , WENDEL, Hans-Peter , NOLTE, Andrea , WALKER, Tobias
发明人： BAUMHOF, Patrick , WENDEL, Hans-Peter , NOLTE, Andrea , WALKER, Tobias
IPC分类号： A61K47/34 , A61K9/51 , A61K47/48 , A61K48/00 , A61L27/34 , A61L27/54 , A61L27/58 , A61L31/10 , A61L31/14 , A61L31/16
CPC分类号： A61K48/0041 , A61K9/5146 , A61K9/5153 , A61K9/5192 , A61K47/34 , A61K47/645 , A61K47/6937 , A61L27/34 , A61L27/54 , A61L31/10 , A61L31/148 , A61L31/16 , A61L2300/258 , A61L2300/604 , A61L2300/606 , A61L2300/62 , A61L2300/802 , A61L2400/12 , C12N9/0069 , C12N15/88 , C12Y113/12005 , C08L67/04
摘要： The present invention relates to nanoparticles comprising nucleic acids coated with a (biodegradable) polymer for reversible immobilization and/or controlled release of the nucleic acid comprising nanoparticles. Furthermore, the present invention is directed to medical or diagnostic devices, particularly stents and implants coated by a (biodegradable) polymer with the nucleic acid comprising nanoparticles for reversible immobilization and/or controlled release. Furthermore, the present invention is directed to the use of these nanoparticles coated with a (biodegradable) polymer and to the use of medical devices and implants coated by the (biodegradable) polymer with these nucleic acid comprising nanoparticles in the prophylactic or therapeutic treatment of diseases, particularly in the prevention or treatment of restenosis, calicification, foreign body reaction, or inflammation. Additionally, the present invention is directed to a method of preparing these nucleic acid comprising nanoparticles coated with a (biodegradable) polymer and to a method for coating nucleic acid comprising nanoparticles by a (biodegradable) polymer on medical or diagnostic devices.
摘要翻译：本发明涉及包含用可生物降解的聚合物涂覆的核酸的纳米颗粒，用于可逆地固定和/或控制释放包含纳米颗粒的核酸。此外，本发明涉及医疗或诊断装置，特别是由可生物降解的聚合物涂覆的支架和植入物，其中核酸包含用于可逆固定和/或控制释放的纳米颗粒。此外，本发明涉及涂覆有（可生物降解的）聚合物的这些纳米颗粒的用途，以及使用包含（可生物降解的）聚合物的医疗装置和植入物，其中包含纳米颗粒的这些核酸在预防或治疗疾病中特别是在预防或治疗再狭窄，加压，异物反应或炎症中。另外，本发明涉及一种制备这些核酸的方法，所述核酸包含涂覆有（可生物降解的）聚合物的纳米颗粒，以及通过医学或诊断装置上的（可生物降解的）聚合物涂覆包含纳米颗粒的核酸的方法。

4. 发明申请

WO2011026641A9 DISULFIDE-LINKED POLYETHYLENEGLYCOL/PEPTIDE CONJUGATES FOR THE TRANSFECTION OF NUCLEIC ACIDS 审中-公开
标题翻译：二硫键连接的聚乙二醇/肽共轭物用于转移核酸
公开(公告)号：WO2011026641A9
公开(公告)日：2011-11-17
申请号：PCT/EP2010005438
申请日：2010-09-03
申请人： CUREVAC GMBH , BAUMHOF PATRICK , SCHLAKE THOMAS
发明人： BAUMHOF PATRICK , SCHLAKE THOMAS
IPC分类号： A61K47/48 , A61P43/00
CPC分类号： A61K48/0041 , A61K47/60 , A61K47/6455
摘要： The present invention is directed to an inventive polymeric carrier molecule according to generic formula (I) and variations thereof, which allows for efficient transfection of nucleic acids into cells in vivo and in vitro, a polymeric carrier cargo complex formed by a nucleic acid and the inventive polymeric carrier molecule, but also to methods of preparation of this inventive polymeric carrier molecule and of the inventive polymeric carrier cargo complex. The present invention also provides methods of application and use of this inventive polymeric carrier molecule and the inventive polymeric carrier cargo complex as a medicament, for the treatment of various diseases, and in the preparation of a pharmaceutical composition for the treatment of such diseases.
摘要翻译：本发明涉及根据通式（I）及其变体的本发明的聚合物载体分子，其允许核酸在体内和体外有效地转染入细胞，由核酸和本发明的聚合物载体分子，还涉及制备本发明的聚合物载体分子和本发明的聚合物载体货物复合物的方法。本发明还提供了本发明的聚合物载体分子和本发明的聚合物载体货物复合物作为药物，用于治疗各种疾病以及制备用于治疗这些疾病的药物组合物的应用和使用方法。

5. 发明申请

WO2010088927A1 USE OF PEI FOR THE IMPROVEMENT OF ENDOSOMAL RELEASE AND EXPRESSION OF TRANSFECTED NUCLEIC ACIDS, COMPLEXED WITH CATIONIC OR POLYCATIONIC COMPOUNDS 审中-公开
标题翻译：使用PEI改进内源性释放和表达转移的核酸，与阳离子或多元化合物复合
公开(公告)号：WO2010088927A1
公开(公告)日：2010-08-12
申请号：PCT/EP2009/000886
申请日：2009-02-09
申请人： CUREVAC GMBH , BAUMHOF, Patrick , SCHLAKE, Thomas
发明人： BAUMHOF, Patrick , SCHLAKE, Thomas
IPC分类号： C12N15/87 , A61K48/00
CPC分类号： C12N15/87 , A61K48/0041
摘要： The present invention is directed to complexed precomplexed nucleic acids, preferably mRNAs, which have been precomplexed in a first step with PEI in an N/P ratio between 0.05 and 2, preferably in an N/P ratio between 0.1 and 1, and which have been further complexed in a second step with a cationic compound. The present invention is furthermore directed to the use of such complexed precomplexed nucleic acids for the improvement of the endosomal release of nucleic acids and optionally the improvement of expression of an encoded protein or peptide. It is also directed to compositions comprising such complexed precomplexed nucleic acids and to the use of such complexed precomplexed nucleic acids or compositions thereof for gene therapy and/or the treatment of various diseases as mentioned herein, e.g. by vaccination. The present invention is also directed to methods for preparing and administering these complexed precomplexed nucleic acids or compositions thereof and to kits, comprising these complexed precomplexed nucleic acids or compositions thereof.
摘要翻译：本发明涉及复合的预复合核酸，优选mRNA，其在第一步中已经被复合，PEI以N / P比为0.05和2，优选N / P比在0.1和1之间，其具有在第二步中与阳离子化合物进一步复合。本发明还涉及这种复合的预复合核酸用于改善核酸的内体内释放和任选地改进编码的蛋白质或肽的表达的用途。还涉及包含这种络合的预复合核酸的组合物，以及这些复合的预复合核酸或其组合物用于基因治疗和/或治疗如本文所述的各种疾病的用途，例如，通过疫苗接种。本发明还涉及用于制备和施用这些络合的预复合核酸或其组合物的方法，以及包含这些络合的预复合核酸或其组合物的试剂盒。

6. 发明申请

WO2013113502A1 NEGATIVELY CHARGED NUCLEIC ACID COMPRISING COMPLEXES FOR IMMUNOSTIMULATION 审中-公开
标题翻译：负责充电的核酸包含免疫复合物
公开(公告)号：WO2013113502A1
公开(公告)日：2013-08-08
申请号：PCT/EP2013/000292
申请日：2013-01-31
申请人： CUREVAC GMBH , BAUMHOF, Patrick
发明人： BAUMHOF, Patrick
IPC分类号： A61K47/48 , A61K39/39 , A61P37/00 , A61P31/00 , A61P35/00
CPC分类号： A61K39/39 , A61K39/0011 , A61K39/12 , A61K39/145 , A61K47/543 , A61K47/59 , A61K47/645 , A61K47/646 , A61K2039/55561 , A61K2039/57 , A61K2039/6031 , C12N2760/16134 , Y02A50/386 , Y02A50/416
摘要： The present invention is directed to a pharmaceutical composition including (e.g., for use as an adjuvant) a (negatively charged) nucleic acid comprising complex comprising as a carrier cationic or polycationic compounds (e.g. peptides, proteins or polymers) and as a cargo at least one nucleic acid (molecule) and at least one antigen that is selected from an antigen from a pathogen associated with infectious disease; an antigen associated with allergy or allergic disease; an antigen associated with autoimmune disease; or an antigen associated with a cancer or tumour disease, or in each case a fragment, variant and/or derivative of said antigen. The pharmaceutical composition allows for efficient induction of an adaptive immune response directed against said antigen. The present invention furthermore provides kits, as well as the use of the pharmaceutical composition or the kit as a vaccine, particularly in the treatment of infectious diseases, allergies, autoimmune diseases and tumour or cancer diseases.
摘要翻译：本发明涉及包含（例如，用作佐剂）的（带负电荷的）核酸的药物组合物，其包含作为载体的阳离子或多阳离子化合物（例如肽，蛋白质或聚合物）和作为货物的至少一种核酸（分子）和至少一种选自与感染性疾病相关的病原体的抗原的抗原; 与过敏或过敏性疾病相关的抗原; 与自身免疫性疾病相关的抗原; 或与癌症或肿瘤疾病相关的抗原，或在每种情况下都是所述抗原的片段，变体和/或衍生物。药物组合物允许有效诱导针对所述抗原的适应性免疫应答。本发明还提供试剂盒，以及药物组合物或试剂盒作为疫苗的用途，特别是用于治疗感染性疾病，过敏反应，自身免疫疾病和肿瘤或癌症疾病。

7. 发明申请

WO2013113325A1 NEGATIVELY CHARGED NUCLEIC ACID COMPRISING COMPLEXES FOR IMMUNOSTIMULATION 审中-公开
标题翻译：负责充电的核酸包含免疫复合物
公开(公告)号：WO2013113325A1
公开(公告)日：2013-08-08
申请号：PCT/EP2012/000418
申请日：2012-01-31
申请人： CUREVAC GMBH , BAUMHOF, Patrick
发明人： BAUMHOF, Patrick
IPC分类号： A61K47/48 , A61K39/39 , A61P37/00 , A61P31/00 , A61P35/00
CPC分类号： A61K39/39 , A61K39/0011 , A61K39/12 , A61K39/145 , A61K47/543 , A61K47/59 , A61K47/645 , A61K47/646 , A61K2039/55561 , A61K2039/57 , A61K2039/6031 , C12N2760/16134 , Y02A50/386 , Y02A50/416
摘要： The present invention is directed to a pharmaceutical composition including (e.g., for use as an adjuvant) a (negatively charged) nucleic acid comprising complex comprising as a carrier cationic or polycationic compounds (e.g. peptides, proteins or polymers) and as a cargo at least one nucleic acid (molecule) and at least one antigen that is selected from an antigen from a pathogen associated with infectious disease;_an antigen associated with allergy or allergic disease; an antigen associated with autoimmune disease; or an antigen associated with a cancer or tumour disease, or in each case a fragment, variant and/or derivative of said antigen. The pharmaceutical composition allows for efficient induction of an adaptive immune response directed against said antigen. The present invention furthermore provides kits, as well as the use of the pharmaceutical composition or the kit as a vaccine, particularly in the treatment of infectious diseases, allergies, autoimmune diseases and tumour or cancer diseases.
摘要翻译：本发明涉及包含（例如，用作佐剂）的（带负电荷的）核酸的药物组合物，其包含作为载体的阳离子或多阳离子化合物（例如肽，蛋白质或聚合物）和作为货物至少一种核酸（分子）和至少一种选自与感染性疾病相关的病原体的抗原的抗原;与过敏或过敏性疾病相关的抗原; 与自身免疫性疾病相关的抗原; 或与癌症或肿瘤疾病相关的抗原，或在每种情况下都是所述抗原的片段，变体和/或衍生物。药物组合物允许有效诱导针对所述抗原的适应性免疫应答。本发明还提供试剂盒，以及药物组合物或试剂盒作为疫苗的用途，特别是用于治疗感染性疾病，过敏反应，自身免疫性疾病和肿瘤或癌症疾病。

8. 发明申请

WO2008043551A1 METHODS AND KIT FOR ISOLATING NUCLEIC ACIDS 审中-公开
标题翻译：分离核酸的方法和工具包
公开(公告)号：WO2008043551A1
公开(公告)日：2008-04-17
申请号：PCT/EP2007/008826
申请日：2007-10-10
申请人： QIAGEN GMBH , RITT, Christoph , ERBACHER, Christoph , BAUMHOF, Patrick
发明人： RITT, Christoph , ERBACHER, Christoph , BAUMHOF, Patrick
IPC分类号： C12N15/10
CPC分类号： C12N15/101 , C12N15/1006 , Y10T436/143333 , Y10T436/255
摘要： The present invention is related to a method for isolating a target nucleic acid from a sample comprising said target nucleic acid, comprising the steps of mixing a sample containing said target nucleic acid with a binding solution and a nucleic acid binding matrix, binding at least part of said target nucleic acid to said nucleic acid binding matrix, wherein said nucleic acid binding matrix is treated simultaneously or has been previously treated with at least one compound comprising a metal substance selected from the group consisting of metals of the main groups 13 to 16, semimetals and transition metals for reducing non-target nucleic acid contaminations or wherein said nucleic acid binding matrix is modified with hydrophobic groups. Furthermore, respective kits and reagents are provided with the teaching of the present invention.
摘要翻译：本发明涉及从包含所述靶核酸的样品中分离靶核酸的方法，包括以下步骤：将含有所述靶核酸的样品与结合溶液和核酸结合基质混合，将至少部分的所述靶核酸与所述核酸结合基质反应，其中所述核酸结合基质同时被处理或已经用至少一种包含选自主要组13至16的金属的金属的化合物进行处理，半金属和过渡金属，用于降低非目标核酸污染物，或其中所述核酸结合基质用疏水基团修饰。此外，本发明的教导提供了相应的试剂盒和试剂。

9. 发明申请

WO2013113501A1 PHARMACEUTICAL COMPOSITION COMPRISING A POLYMERIC CARRIER CARGO COMPLEX AND AT LEAST ONE PROTEIN OR PEPIDE ANTIGEN 审中-公开
标题翻译：包含聚合物载体复合物和至少一种蛋白质或抗原抗原的药物组合物
公开(公告)号：WO2013113501A1
公开(公告)日：2013-08-08
申请号：PCT/EP2013/000291
申请日：2013-01-31
申请人： CUREVAC GMBH , BAUMHOF, Patrick , KRAMPS, Thomas , VOSS, Söhnke , KALLEN, Karl-Josef , FOTIN-MLECZEK, Mariola
发明人： BAUMHOF, Patrick , KRAMPS, Thomas , VOSS, Söhnke , KALLEN, Karl-Josef , FOTIN-MLECZEK, Mariola
IPC分类号： A61K47/48 , A61K39/39 , A61P35/00 , A61P37/00 , A61P31/00
CPC分类号： A61K39/39 , A61K39/0011 , A61K39/12 , A61K39/145 , A61K39/205 , A61K39/29 , A61K39/35 , A61K47/64 , A61K47/645 , A61K47/646 , A61K48/0041 , A61K2039/5252 , A61K2039/53 , A61K2039/55511 , A61K2039/55516 , A61K2039/55561 , A61K2039/572 , A61K2039/575 , A61K2039/6093 , C12N7/00 , C12N2710/20034 , C12N2710/20071 , C12N2730/10134 , C12N2730/10171 , C12N2760/16134 , C12N2760/16171 , C12N2760/20134 , C12N2760/20171 , Y02A50/416
摘要： The present invention is directed to a pharmaceutical composition including (e.g. for use as an adjuvant) a polymeric carrier cargo complex, comprising as a carrier a polymeric carrier formed by disulfide-crosslinked cationic components; and as a cargo at least one nucleic acid molecule, and at least one antigen that is selected from an antigen from a pathogen associated with infectious disease; an antigen associated with allergy or allergic disease; an antigen associated with autoimmune disease; or an antigen associated with a cancer or tumour disease, or in each case a fragment, variant and/or derivative of said antigen. The pharmaceutical composition allows for efficient induction of an adaptive immune response directed against said antigen. The present invention furthermore provides kits, as well as the use of the pharmaceutical composition or the kit as a vaccine, particularly in the treatment of infectious diseases, allergies, autoimmune diseases and tumour or cancer diseases.
摘要翻译：本发明涉及包含（例如用作佐剂）聚合物载体货物复合物的药物组合物，其包含作为载体的由二硫化物交联的阳离子组分形成的聚合物载体; 以及作为货物至少一种核酸分子和至少一种选自与感染性疾病相关的病原体的抗原的抗原; 与过敏或过敏性疾病相关的抗原; 与自身免疫性疾病相关的抗原; 或与癌症或肿瘤疾病相关的抗原，或在每种情况下都是所述抗原的片段，变体和/或衍生物。药物组合物允许有效诱导针对所述抗原的适应性免疫应答。本发明还提供试剂盒，以及药物组合物或试剂盒作为疫苗的用途，特别是用于治疗感染性疾病，过敏反应，自身免疫性疾病和肿瘤或癌症疾病。

10. 发明申请

WO2012113413A1 VACCINE COMPOSITION COMPRISING COMPLEXED IMMUNOSTIMULATORY NUCLEIC ACIDS AND ANTIGENS PACKAGED WITH DISULFIDE-LINKED POLYETHYLENEGLYCOL/PEPTIDE CONJUGATES 审中-公开
标题翻译：包含复合免疫细胞核酸的疫苗组合物和用分离的聚乙二醇/肽结合物包装的抗体
公开(公告)号：WO2012113413A1
公开(公告)日：2012-08-30
申请号：PCT/EP2011/000827
申请日：2011-02-21
申请人： CUREVAC GMBH , BAUMHOF, Patrick , KALLEN, Karl-Josef , FOTIN-MLECZEK, Mariola
发明人： BAUMHOF, Patrick , KALLEN, Karl-Josef , FOTIN-MLECZEK, Mariola
IPC分类号： A61K47/48
CPC分类号： A61K39/39 , A61K39/0011 , A61K47/48092 , A61K47/481 , A61K47/48215 , A61K47/48323 , A61K47/549 , A61K47/55 , A61K47/60 , A61K47/6455 , A61K2039/53 , A61K2039/55561 , A61K2039/57 , A61K2039/575
摘要： The present invention is directed to a composition or vaccine composition comprising a) an adjuvant component comprising or consisting of at least one immunostimulatory nucleic acid sequence, complexed with a complexing agent; b) an antigen, preferably a protein or peptide antigen and/or a nucleic acid sequence encoding said antigen; and c) a carrier molecule for combined packaging the adjuvant component and the antigen. The present invention is also directed to the first medical use of such a composition or vaccine composition and to the second medical use of such a composition or vaccine composition or components thereof for the treatment of diseases, such as infectious or cancer or tumour diseases as defined herein. The present invention furthermore discloses kits comprising such a composition or vaccine composition.
摘要翻译：本发明涉及一种组合物或疫苗组合物，其包含a）包含与由络合剂络合的至少一种免疫刺激核酸序列或由其组成的佐剂组分; b）抗原，优选蛋白质或肽抗原和/或编码所述抗原的核酸序列; 和c）用于将佐剂组分和抗原组合包装的载体分子。本发明还涉及这种组合物或疫苗组合物的第一医疗用途以及这种组合物或疫苗组合物或其组分的第二医疗用途，用于治疗疾病如感染性或癌症或定义的肿瘤疾病于此。本发明还公开了包含这种组合物或疫苗组合物的试剂盒。

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