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1. 发明申请

WO03059381A2 IMMUNOGENIC PREPARATIONS AND VACCINES ON THE BASIS OF RNA 审中-公开
标题翻译：基于RNA的免疫制备和疫苗
公开(公告)号：WO03059381A2
公开(公告)日：2003-07-24
申请号：PCT/EP0300497
申请日：2003-01-20
申请人： CUREVAC GMBH , PASTEUR INSTITUT , INST NAT SANTE RECH MED , GENETHON III , PASCOLO STEVE CYRIL , HOERR INGMAR , RAMMENSEE HANS-GEORG , VON DER MUELBE FLORIAN , MICHEL MARIE-LOUISE , FIRAT HUESEYIN , LEMONNIER FRANCOIS ALBERT
发明人： PASCOLO STEVE CYRIL , HOERR INGMAR , RAMMENSEE HANS-GEORG , VON DER MUELBE FLORIAN , MICHEL MARIE-LOUISE , FIRAT HUESEYIN , LEMONNIER FRANCOIS ALBERT
IPC分类号： A61K39/21 , A61K39/29 , A61K48/00 , A61P31/00 , A61P31/18 , A61P31/20 , C07K14/02 , C07K14/16 , A61K39/00
CPC分类号： C07K14/005 , A61K39/12 , A61K39/21 , A61K39/29 , A61K39/292 , A61K48/00 , A61K2039/53 , A61K2039/55516 , A61K2039/55522 , C12N2730/10122 , C12N2730/10134 , C12N2740/16022 , C12N2740/16034 , C12N2770/24222 , C12N2770/24234
摘要： The present invention relates to the field of vaccination and immune stimulation by the use of nucleic acids, in particular RNA, coding for one or more antigens of pathogenic micro organisms.
摘要翻译：本发明涉及通过使用编码一种或多种病原微生物抗原的核酸，特别是RNA来进行疫苗接种和免疫刺激的领域。

2. 发明申请

WO0244202A2 MUTATED IMMUNOGENIC PEPTIDES DERIVED FROM R9M, POLYNUCLEOTIDES CODING FOR SAME AND THERAPEUTIC USES THEREOF 审中-公开
标题翻译：从R9M衍生的突变型免疫原性肽，其编码的多核苷酸及其治疗用途
公开(公告)号：WO0244202A2
公开(公告)日：2002-06-06
申请号：PCT/FR0103779
申请日：2001-11-29
申请人： PASTEUR INSTITUT , INST NAT SANTE RECH MED , ASSIST PUBL HOPITAUX DE PARIS , FIRAT HUESEYIN , LANGLADE DEMOYAN PIERRE , VILMER ETIENNE , LEMONNIER FRANCOIS , ROHRLICH PIERRE , YOTNDA PATRICIA
发明人： FIRAT HUESEYIN , LANGLADE-DEMOYAN PIERRE , VILMER ETIENNE , LEMONNIER FRANCOIS , ROHRLICH PIERRE , YOTNDA PATRICIA
IPC分类号： A61K35/17 , A61K38/00 , A61K39/00 , A61P35/02 , C07K14/47 , C12N5/18 , C12N15/12 , C07K7/00
CPC分类号： C07K14/4748 , A61K38/00 , A61K39/00
摘要： The invention concerns the optimisation of the wild R9M peptide and the use of the resulting peptides for therapeutic vaccination and/or preventive vaccination against leukaemia in humans. More particularly, the invention concerns mutated immunogenic peptides derived from the human TEL/AML1 fusion protein comprising the wild R9M peptide sequence Arg-IIe-Ala-Glu-Cys-IIe-Leu-Gly-Met. The invention also concerns polynucleotides coding for the mutated R9M immunogenic peptides, cellular expression vectors comprising nucleic acid sequences expressing the mutated R9M immunogenic peptides and polyclonal or monoclonal antibodies capable of being fixed on at least one of said peptides/polynucleotides. The invention further concerns the use of said peptides, polynucleotides and/or antibodies for preparing vaccines, anti-tumoral medicines and compositions and for in vitro and in vivo stimulation of the immune response in humans.
摘要翻译：本发明涉及野生R9M肽的优化和所得肽用于人类白血病的治疗性接种和/或预防性接种的用途。更具体地，本发明涉及衍生自包含野生型R9M肽序列Arg-IIe-Ala-Glu-Cys-IIe-Leu-Gly-Met的人TEL / AML1融合蛋白的突变的免疫原性肽。本发明还涉及编码突变的R9M免疫原性肽的多核苷酸，包含表达突变的R9M免疫原性肽的核酸序列的细胞表达载体和能够固定在至少一种所述肽/多核苷酸上的多克隆或单克隆抗体。本发明还涉及所述肽，多核苷酸和/或抗体在制备疫苗，抗肿瘤药物和组合物中的用途，并且在体内< 刺激人体免疫反应。

3. 发明申请

WO0123577A3 HYBRID OR CHIMERIC POLYNUCLEOTIDES, PROTEINS, AND COMPOSITIONS COMPRISING HEPATITIS B VIRUS SEQUENCES 审中-公开
标题翻译：包含乙型肝炎病毒序列的杂合或嵌合多核苷酸，蛋白质和组合物
公开(公告)号：WO0123577A3
公开(公告)日：2001-05-17
申请号：PCT/EP0009900
申请日：2000-09-29
申请人： PASTEUR INSTITUT , FIRAT HUESEYIN , LEMONNIER FRANCOIS , LANGLADE DEMOYEN PIERRE , MICHEL MARIE LOUISE , SUHRBIER ANDREAS A
发明人： FIRAT HUESEYIN , LEMONNIER FRANCOIS , LANGLADE-DEMOYEN PIERRE , MICHEL MARIE-LOUISE , A SUHRBIER ANDREAS
IPC分类号： A61K48/00 , C07K14/02 , C12N7/01 , C12N15/36 , C12N15/62
CPC分类号： C07K14/005 , A61K39/0011 , A61K39/12 , A61K39/292 , A61K48/00 , A61K2039/5258 , A61K2039/57 , C07K2319/00 , C07K2319/40 , C12N2730/10122 , C12N2730/10134
摘要： H-2 class I negative, HLA-A2.1 transgenic HHD mice were used for a comparative evaluation of the immunogenicity of HLA-A2.1 restricted human tumor-associated CTL epitopes. A hierarchy was established among these epitopic peptides injected into mice in IFA which correlates globally with their capacity to bind and stabilize HLA-A2.1 molecules. Co-injection of a helper peptide enhanced most CTL responses. In contrast, classical HLA class I transgenic mice which still express their own class I molecules did not, in most cases, develop H.A.-A2.1-restricted CTL responses under the same experimental conditions. Different monoepitopic immunization strategies of acceptable clinical usage were compared in HHD mice. Recombinant Ty-virus-like particles, or DNA encoding epitopes fused to the hepatitis B virus middle envelope protein gave the best results. Using this latter approach and a melanoma-based polyepitope construct, CTL responses against five distinct epitopes could be elicited simultaneously in a single animal. Thus, HHD mice provide a versatile animal model for preclinical evaluation of peptide-based cancer immunotherapy.
摘要翻译： H-2 I类阴性HLA-A2.1转基因HHD小鼠用于HLA-A2.1限制性人肿瘤相关CTL表位免疫原性的比较评估。在注射到IFA小鼠中的这些表位肽之间建立了等级，其与它们结合和稳定HLA-A2.1分子的能力在全局上相关。共注射辅助肽增强了大多数CTL应答。相反，仍然表达它们自己的I类分子的经典HLA I类转基因小鼠在大多数情况下在相同的实验条件下不发展H.A.-A2.1限制性CTL应答。在HHD小鼠中比较了可接受的临床使用的不同单表位免疫策略。重组的Ty-病毒样颗粒或编码与乙型肝炎病毒中间包膜蛋白融合的表位的DNA给出最佳结果。使用后一种方法和基于黑素瘤的多表位构建体，可以在单一动物中同时引发针对五种不同表位的CTL应答。因此，HHD小鼠提供了用于基于肽的癌症免疫疗法的临床前评估的通用动物模型。

4. 发明申请

WO0127291A9 DESIGN OF A POLYEPITOPIC CONSTRUCT FOR THE INDUCTION OF HLA-A2.1 RESTRICTED HIV 1 SPECIFIC CTL RESPONSES USING HHD MICE 审中-公开
标题翻译：用于诱导HLA-A2.1限制性HIV的多功能构建体的设计使用HHD MICE的特异性CTL应答
公开(公告)号：WO0127291A9
公开(公告)日：2002-09-06
申请号：PCT/EP0009902
申请日：2000-09-29
申请人： PASTEUR INSTITUT , FIRAT HUESEYIN , LEMONNIER FRANCOIS , LANGLADE-DEMOYEN PIERRE
发明人： FIRAT HUESEYIN , LEMONNIER FRANCOIS , LANGLADE-DEMOYEN PIERRE
IPC分类号： A61K39/00 , C07K14/02 , C07K14/16 , C12N15/62 , A61K39/21 , A61K39/29
CPC分类号： C07K14/005 , A61K39/00 , A61K2039/53 , C07K2319/00 , C07K2319/40 , C12N15/62 , C12N2730/10122 , C12N2740/16122 , C12N2740/16222 , C12N2740/16322
摘要： H-2 class I negative, HLA-A2.1 transgenic HHD mice were used for a comparative evaluation of the immunogenicity of HLA-A2.1 restricted human tumour-associated CTL epitopes and HIV 1-derived epitopes. A hierarchy was established among these epitopic peptides injected into mice in IFA which correlates globally with their capacity to bind and stabilize HLA-A2.1 molecules. A tyrosine substitution in position 1 of the HIV 1-derived epitopic peptides, which increases both their affinity for and their HLA-A2.1 molecule stabilizing capacity, was introduced in a significant proportion of them. DNA immunizations were performed using a construct comprising nucleic acids encoding the epitopes inserted into the pre-S2 segment of the hepatitis B middle glycoprotein. CTL responses against most of the inserted epitopes could be elicited simultaneously in a single animal.
摘要翻译：使用H-2类I阴性，HLA-A2.1转基因HHD小鼠进行HLA-A2.1限制性人肿瘤相关CTL表位和HIV1-衍生表位的免疫原性的比较评估。在IFA中注射到小鼠中的这些表位肽之间建立了等级关系，其与其与结合和稳定HLA-A2.1分子的能力全球相关。在其中很大一部分引入了HIV 1衍生的表位肽的位置1中的酪氨酸取代，其增加了它们对HLA-A2.1分子稳定能力的亲和力和HLA-A2.1分子稳定能力。使用构建体进行DNA免疫，所述构建体包含编码插入到乙型肝炎中间糖蛋白的前S2区段内的表位的核酸。大多数插入的表位的CTL反应可以在单个动物中同时引发。

5. 发明申请

WO2006095259A3 BIOMARKERS FOR CARDIOVASCULAR SIDE-EFFECTS INDUCED BY COX-2 INHIBITORY COMPOUNDS 审中-公开
标题翻译：由COX-2抑制化合物引起的心脏血管副作用的生物标志物
公开(公告)号：WO2006095259A3
公开(公告)日：2007-01-04
申请号：PCT/IB2006000533
申请日：2006-03-10
申请人： NOVARTIS AG , NOVARTIS PHARMA GMBH , FIRAT HUESEYIN , BOISCLAIR JULIE , GRENET OLIVIER , PERENTES ELIAS , SCHUMACHER MARTIN M
发明人： FIRAT HUESEYIN , BOISCLAIR JULIE , GRENET OLIVIER , PERENTES ELIAS , SCHUMACHER MARTIN M
IPC分类号： G01N33/53 , A61K45/06 , C12Q1/68
CPC分类号： C12Q1/6883 , A61K31/00 , C12Q2600/106 , C12Q2600/142 , C12Q2600/158 , G01N33/68 , G01N2800/328
摘要： Cardiovascular tissue mRNA expression profiles in monkeys treated with coxibs was analyzed. Genomic data indicated that the animals showing vasculitis exhibit a specific mRNA expression pattern. The pattern includes gene expression changes involved in blood and endothelial cell (EC) activation, interaction of blood cells with EC, activation of INF? pathway, and release of pro-inflammatory cytokines and chemo-attractants. These results provide direct evidence of minimal vasculitis together with corresponding genomic signature and peripheral biomarkers for minimal vasculatis. These results also suggest that treatment might triggers/aggravate a clinically latent cardiovascular disorder in the context of an endothelium tropic viral infection and/or an autoimmune vascular disorder. The histopathological examination revealed marginal vascular changes consistent with the genomic findings. Measurement of soluble proteins present in serum and plasma using a multiplex assay were in line with the genomic results, showing the increasedlevel of INF? inducible proteins, increased expression of CXCL10 chemokine was confirmed by an ELISA both in serum and plasma. Use of these peripheral biomarkers allows a safe usage of cox-2 inhibitory compounds in clinics and selection of cox-2 inhibitory follow-up compounds with no cardiovascular toxicity. These data together with biochemical and histopathological findings suggest that the specific cox2 inhibitor may exaggerate host immune response during some specific viral infections with endothelial tropism, or subjacent vascular autoimmune disorders.
摘要翻译：分析了用coxibs处理的猴子的心血管组织mRNA表达谱。基因组数据表明，显示血管炎的动物表现出特异的mRNA表达模式。该模式包括参与血液和内皮细胞（EC）激活的基因表达变化，血细胞与EC的相互作用，INF的激活途径和促炎细胞因子和化学引诱物的释放。这些结果提供了最小血管炎的直接证据以及相应的基因组特征和用于最小血管平滑肌的外周生物标志物。这些结果还表明治疗可能在内皮热带病毒感染和/或自身免疫性血管疾病的背景下触发/加重临床上潜在的心血管疾病。组织病理学检查发现边缘血管变化与基因组结果一致。使用多重测定法测定血清和血浆中的可溶性蛋白质与基因组结果一致，显示出INF的水平升高通过血清和血浆中的ELISA证实可诱导蛋白，CXCL10趋化因子表达增加。使用这些外周生物标志物可以安全使用cox-2抑制性化合物在临床和选择没有心血管毒性的cox-2抑制性后续化合物。这些数据连同生物化学和组织病理学研究结果表明，特定的cox2抑制剂可能在具有内皮向性或下部血管自身免疫疾病的特定病毒感染期间夸大宿主免疫应答。

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