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1. 发明申请

WO2014150150A1 ENHANCED EXPRESSION OF PICORNAVIRUS PROTEINS 审中-公开
标题翻译：丝氨酸蛋白酶的增强表达
公开(公告)号：WO2014150150A1
公开(公告)日：2014-09-25
申请号：PCT/US2014/022399
申请日：2014-03-10
申请人： NOVAVAX, INC.
发明人： MASSARE, Michael J.
IPC分类号： C12N15/62 , C07K7/08 , C07K14/09 , C12N5/10 , A61K39/135
CPC分类号： C07K14/005 , A61K39/12 , A61K39/135 , A61K47/646 , C07K2319/02 , C07K2319/21 , C07K2319/40 , C12N7/00 , C12N2760/16122 , C12N2770/32122 , C12N2770/32134 , C12N2770/32151
摘要： The disclosure provides fusion proteins containing N-terminal signal peptides fused to immunogenic polypeptides. The immunogenic polypeptides may be from viruses, bacteria, or fungi. The disclosure also provides elevated expression of the immunogenic polypeptides using the N-terminal signal peptide. The N-terminal signal peptides enhance synthesis of the protein, particularly where the protein is neither a secretory nor a transmembrane peptide. The fusion proteins may be used to diagnose disease and to induce immune responses.
摘要翻译：本公开提供了融合蛋白质，其含有与免疫原性多肽融合的N-末端信号肽。免疫原性多肽可以来自病毒，细菌或真菌。本公开还提供使用N-末端信号肽的免疫原性多肽的升高的表达。 N端信号肽增强了蛋白质的合成，特别是蛋白质既不是分泌型也不是跨膜肽的情况。融合蛋白可用于诊断疾病和诱导免疫应答。

2. 发明申请

WO2012003129A2 DEVELOPMENT OF A MARKER FOOT AND MOUTH DISEASE VIRUS VACCINE CANDIDATE THAT IS ATTENUATED IN THE NATURAL HOST 审中-公开
标题翻译：在天然宿主中降解标记基因和口腔病毒疫苗候选株的研制
公开(公告)号：WO2012003129A2
公开(公告)日：2012-01-05
申请号：PCT/US2011/041567
申请日：2011-06-23
申请人： THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY OF AGRICULTURE , RIEDER, Aida E. , RODRIGUEZ, Luis L. , HOLLISTER, Jason R. , UDDOWLA, Sabena
发明人： RIEDER, Aida E. , RODRIGUEZ, Luis L. , HOLLISTER, Jason R. , UDDOWLA, Sabena
IPC分类号： C12N15/42 , A61K39/135 , C12N15/86 , C12Q1/70
CPC分类号： C07K14/005 , A61K39/12 , A61K39/135 , A61K2039/5252 , A61K2039/5254 , A61K2039/552 , A61K2039/55566 , C12N7/00 , C12N2770/32121 , C12N2770/32122 , C12N2770/32134 , C12N2770/32151 , C12N2770/32162 , C12N2770/32163 , C12N2770/32171 , C12Q1/701 , G01N33/56983 , G01N2469/10
摘要： We have generated novel molecularly marked FMDV A 24 LL3D YR and A 24 LL3B PVKV 3D YR vaccine candidates. The mutant viruses contain a deletion of the leader coding region (LL) rendering the virus attenuated in vivo and negative antigenic markers introduced in one or both of the viral non-structural 3D pol and 3B proteins. Mutations were introduced into MAb F32-44 epitope in FMDV A24Cruzeiro spanning residues H 27 N 31 in 3 Dpol protein to obtain the homologous amino acid sequence of bovine rhinitis virus type B (BRV-2, Y 27 R 31 ). Mutations in 3B consisted of a deletion of 3B 1 and a mutation in 3B 2 (RQKP->PVKV, found in BRV-2) that abolishes reactivity with MAb F8B. These attenuated marker viruses provide safe alternatives for FMD vaccine manufacturing. The vaccine platform includes unique restriction endonuclease sites for easy swapping of capsid proteins for different FMDV subtypes and serotypes. Chimeric viruses were produced to contain the capsid of distantly related type A/Turkey/06 or Asia type FMDV: Asia1-A 24 LL3B PVKV 3D YR and A/Turkey/06 -A 24 LL3B PVKV 3D YR . A2 4 LL3D YR and A 24 LL3B PVKV 3D YR mutant viruses produced no signs of FMD and no shedding of virulent virus in cattle. No clinical signs of disease or fever were observed and no transmission to in-contact animals was detected in pigs inoculated with live A24LL3DYR or the chimeric A-Turkey/06-A 24 LL3B PVKV 3D YR or Asia1-A 24 LL3B PVKV 3D YR viruses. Cattle immunized with chemically inactivated A24LL3DYR and A 24 LL3B PVKV 3D YR vaccine candidates showed an efficacy comparable to a polyvalent commercial FMDV vaccine and protected 100% the animals from challenge with parental virus. The single and double marked-FMDV vaccine candidates used in conjunction with a cELISA provide a suitable target for DIVA companion tests.
摘要翻译：我们已经产生了新的分子标记的FMDV A 24 LL3DYYR和A 24 LL3B PVKV， 3D> YR疫苗候选物。突变病毒含有导致病毒在体内减毒的前导编码区（LL）缺失和在病毒非结构3D pol和3B蛋白之一或两者中引入的阴性抗原标志物。将突变导入3'Dpol蛋白中FMDV A24Cruzeiro跨越残基H27N31的MAb F32-44表位中以获得同源氨基酸序列的B型牛鼻炎病毒（BRV-2，Y27R31）。 3B中的突变由3B1的缺失和3B2（RQKP-＆gt; PVKV，在BRV-2中发现）中的突变组成，其消除了与MAb F8B的反应性。这些减毒标记病毒为口蹄疫疫苗制造提供了安全的选择。该疫苗平台包含独特的限制性内切酶位点，以便于更换不同FMDV亚型和血清型的衣壳蛋白。产生嵌合病毒以包含远缘相关的A / Turkey / 06型或亚洲型FMDV的衣壳：Asia1-A24 LL3B-PVKV 3D-YR 和A /土耳其/ 06 -A <24> LL3B YR 。 A2 4 LL3DYYR和A244 LL3B PVKV 3DYR突变体病毒产生无口蹄疫的迹象以及牛群中没有病毒流出。在接种活A24LL3DYR或嵌合A-Turkey / 06-A24 LL3B PVKV的猪中没有观察到疾病或发热的临床体征并且未检测到接触性动物的传播。亚型YR亚型或Asia1-A24型LL3B亚型PVKV 3DYR亚型病毒。用化学灭活的A24LL3DYR和A24LL3BVVKV 3DYR候选疫苗候选物免疫接种的牛表现出与多价商业FMDV疫苗相当的功效并且保护了100％来自亲代病毒攻击的动物。与cELISA结合使用的单标记和双标记FMDV候选疫苗为DIVA伴侣测试提供了合适的目标。

3. 发明申请

WO2009114831A2 PROCESS TO PRODUCE FIBRILLAR PROTEINS AND METHOD OF TREATING USING FIBRILLAR PROTEINS 审中-公开
标题翻译：生产纤维蛋白的方法和使用纤维蛋白处理的方法
公开(公告)号：WO2009114831A2
公开(公告)日：2009-09-17
申请号：PCT/US2009/037196
申请日：2009-03-13
申请人： ACADEMIA SINICA , LIANG, Shu-Mei , LIANG, Chi-Ming , CHEN, Yen-Po , HUANG, Chun-Yung
发明人： LIANG, Chi-Ming , CHEN, Yen-Po , HUANG, Chun-Yung
IPC分类号： C07K1/107 , C07K1/14 , C07K14/47 , A61K38/17 , A61P35/00
CPC分类号： C07K1/1136 , A61K38/162 , A61K38/38 , A61K38/39 , C07K14/765 , C07K14/78 , C12N2770/32122 , C12N2770/32151
摘要： A method for changing a globular protein structure into a fibrillar protein structure. The method comprising the steps of providing a globular protein, forming a solution containing the globular protein, adding a detergent to the solution containing the globular protein, applying the solution to a molecular sizing column with a pore size of at least 70 kDa and eluting with a solution containing detergent. A method for changing an unfolded protein structure into a fibrillar protein structure. The method comprising the steps of providing a globular protein, forming a solution containing the globular protein, adding a urea to the solution to unfold the globular protein, applying the solution to a molecular sizing column and eluting with a solution containing detergent. A method for treating cancer comprising the steps of providing a protein, changing the protein into a fibrillar structure, and administering a therapeutically effective amount of the fibrillar structure protein to a patient in need thereof. A method for producing a vaccine adjuvant or antigen adjuvant comprising the steps of providing a protein, and changing the protein into a fibrillar structure.
摘要翻译：一种将球状蛋白结构变为纤维状蛋白结构的方法。该方法包括以下步骤：提供球状蛋白质，形成含有球状蛋白质的溶液，向含有球状蛋白质的溶液中加入洗涤剂，将溶液施加至孔径至少为70kDa的分子筛分柱，并用含有洗涤剂的溶液。将展开的蛋白质结构改变成纤维蛋白结构的方法。该方法包括以下步骤：提供球状蛋白质，形成含有球状蛋白质的溶液，向溶液中加入尿素以展开球状蛋白质，将溶液施加到分子筛分柱上并用含有洗涤剂的溶液洗脱。一种治疗癌症的方法，包括提供蛋白质，将蛋白质改变成纤维结构，以及向有需要的患者施用治疗有效量的纤维结构蛋白的步骤。一种用于生产疫苗佐剂或抗原佐剂的方法，包括提供蛋白质并将蛋白质变成纤维结构的步骤。

4. 发明申请

WO2009114831A3 PROCESS TO PRODUCE FIBRILLAR PROTEINS AND METHOD OF TREATING USING FIBRILLAR PROTEINS 审中-公开
标题翻译：生产纤维蛋白蛋白的方法和使用纤维蛋白蛋白的治疗方法
公开(公告)号：WO2009114831A3
公开(公告)日：2009-10-22
申请号：PCT/US2009037196
申请日：2009-03-13
申请人： ACADEMIA SINICA , LIANG SHU MEI , LIANG CHI-MING , CHEN YEN-PO , HUANG CHUN-YUNG
发明人： LIANG CHI-MING , CHEN YEN-PO , HUANG CHUN-YUNG
IPC分类号： C07K1/107 , A61K38/17 , A61P35/00 , C07K1/14 , C07K14/47
CPC分类号： C07K1/1136 , A61K38/162 , A61K38/38 , A61K38/39 , C07K14/765 , C07K14/78 , C12N2770/32122 , C12N2770/32151
摘要： A method for changing a globular protein structure into a fibrillar protein structure. The method comprising the steps of providing a globular protein, forming a solution containing the globular protein, adding a detergent to the solution containing the globular protein, applying the solution to a molecular sizing column with a pore size of at least 70 kDa and eluting with a solution containing detergent. A method for changing an unfolded protein structure into a fibrillar protein structure. The method comprising the steps of providing a globular protein, forming a solution containing the globular protein, adding a urea to the solution to unfold the globular protein, applying the solution to a molecular sizing column and eluting with a solution containing detergent. A method for treating cancer comprising the steps of providing a protein, changing the protein into a fibrillar structure, and administering a therapeutically effective amount of the fibrillar structure protein to a patient in need thereof. A method for producing a vaccine adjuvant or antigen adjuvant comprising the steps of providing a protein, and changing the protein into a fibrillar structure.
摘要翻译：一种将球状蛋白质结构变为纤维状蛋白质结构的方法。该方法包括以下步骤：提供球状蛋白质，形成含有球状蛋白质的溶液，向含有球状蛋白质的溶液中加入去污剂，将该溶液应用于孔径至少为70kDa的分子筛分柱，并用含有清洁剂的溶液。一种将未折叠的蛋白质结构变为纤维状蛋白质结构的方法。该方法包括以下步骤：提供球状蛋白质，形成含有球状蛋白质的溶液，向溶液中加入尿素以展开球状蛋白质，将溶液施加到分子大小柱上并用含有去污剂的溶液洗脱。一种治疗癌症的方法，包括以下步骤：提供蛋白质，将蛋白质变为纤维状结构，并将治疗有效量的纤维状结构蛋白给予有需要的患者。生产疫苗佐剂或抗原佐剂的方法，包括提供蛋白质和将蛋白质变成纤维状结构的步骤。

5. 发明申请

WO2008114021A1 METHOD FOR PRESERVING VIRAL PARTICLES 审中-公开
标题翻译：保存病毒颗粒的方法
公开(公告)号：WO2008114021A1
公开(公告)日：2008-09-25
申请号：PCT/GB2008/000987
申请日：2008-03-19
申请人： STABILITECH LTD. , DREW, Jeffrey
发明人： DREW, Jeffrey
IPC分类号： C12N1/04 , A61K35/76 , A61K47/26 , A61K47/30
CPC分类号： C12N7/00 , C12N2770/32151
摘要： A method for preserving viral particles comprises: (i) providing an aqueous solution of one or more sugars, a polyethyleneimine and said viral particles wherein the concentration of polyethyleneimine is 15 μM or less based on the number-average molar mass (M n ) of the polyethyleneimine and the sugar concentration or, if more than one sugar is present, total sugar concentration is greater than 0.1 M; and (ii) drying the solution to form an amorphous solid matrix comprising said viral particles.
摘要翻译：一种用于保存病毒颗粒的方法包括：（i）提供一种或多种糖，聚乙烯亚胺和所述病毒颗粒的水溶液，其中聚乙烯亚胺的浓度基于数均摩尔质量为15μM或更低 n）和糖浓度，或者如果存在多于一种糖，总糖浓度大于0.1M; 和（ii）干燥溶液以形成包含所述病毒颗粒的无定形固体基质。

6. 发明申请

WO2014154655A1 STABILISED FMDV CAPSIDS 审中-公开
标题翻译：稳定FMDV CAPSIDS
公开(公告)号：WO2014154655A1
公开(公告)日：2014-10-02
申请号：PCT/EP2014/055904
申请日：2014-03-25
申请人： THE PIRBRIGHT INSTITUTE
发明人： KOTECHA, Abhay , STUART, David , FRY, Elizabeth , ESNOUF, Robert
IPC分类号： A61K39/135 , C07K14/005
CPC分类号： C07K14/005 , A61K39/12 , A61K39/135 , A61K2039/5258 , A61K2039/552 , C12N7/00 , C12N2770/32122 , C12N2770/32123 , C12N2770/32134 , C12N2770/32151
摘要： The present invention relates to the stabilisation of foot-and-mouth disease virus (FMDV) capsids, by specific substitution of amino acids in a specific region of FMDV VP2. The invention provides stabilised FMDV capsids and vaccines against FMD.
摘要翻译：本发明涉及口蹄疫病毒（FMDV）衣壳的稳定化，通过特异性取代FMDV VP2的特定区域中的氨基酸。本发明提供了稳定的FMDV衣壳和针对FMD的疫苗。

7. 发明申请

WO2012003129A3 DEVELOPMENT OF A MARKER FOOT AND MOUTH DISEASE VIRUS VACCINE CANDIDATE THAT IS ATTENUATED IN THE NATURAL HOST 审中-公开
标题翻译：发展自然生物和自然病毒的病毒疫苗病毒候选人的发展
公开(公告)号：WO2012003129A3
公开(公告)日：2012-07-05
申请号：PCT/US2011041567
申请日：2011-06-23
申请人： US AGRICULTURE , RIEDER AIDA E , RODRIGUEZ LUIS L , HOLLISTER JASON R , UDDOWLA SABENA
发明人： RIEDER AIDA E , RODRIGUEZ LUIS L , HOLLISTER JASON R , UDDOWLA SABENA
IPC分类号： C12N15/42 , A61K39/135 , C12N15/86 , C12Q1/70
CPC分类号： C07K14/005 , A61K39/12 , A61K39/135 , A61K2039/5252 , A61K2039/5254 , A61K2039/552 , A61K2039/55566 , C12N7/00 , C12N2770/32121 , C12N2770/32122 , C12N2770/32134 , C12N2770/32151 , C12N2770/32162 , C12N2770/32163 , C12N2770/32171 , C12Q1/701 , G01N33/56983 , G01N2469/10
摘要： We have generated novel molecularly marked FMDV A24LL3DYR and A24LL3BPVKV3DYR vaccine candidates. The mutant viruses contain a deletion of the leader coding region (LL) rendering the virus attenuated in vivo and negative antigenic markers introduced in one or both of the viral non-structural 3Dpol and 3B proteins. Mutations were introduced into MAb F32-44 epitope in FMDV A24Cruzeiro spanning residues H27N31 in 3Dpol protein to obtain the homologous amino acid sequence of bovine rhinitis virus type B (BRV-2, Y27R31). Mutations in 3B consisted of a deletion of 3B1 and a mutation in 3B2 (RQKP->PVKV, found in BRV-2) that abolishes reactivity with MAb F8B. These attenuated marker viruses provide safe alternatives for FMD vaccine manufacturing. The vaccine platform includes unique restriction endonuclease sites for easy swapping of capsid proteins for different FMDV subtypes and serotypes. Chimeric viruses were produced to contain the capsid of distantly related type A/Turkey/06 or Asia type FMDV: Asia1-A24LL3BPVKV3DYR and A/Turkey/06 -A24LL3BPVKV3DYR. A24LL3DYR and A24LL3BPVKV3DYR mutant viruses produced no signs of FMD and no shedding of virulent virus in cattle. No clinical signs of disease or fever were observed and no transmission to in-contact animals was detected in pigs inoculated with live A24LL3DYR or the chimeric A-Turkey/06-A24LL3BPVKV3DYR or Asia1-A24LL3BPVKV3DYR viruses. Cattle immunized with chemically inactivated A24LL3DYR and A24LL3BPVKV3DYRvaccine candidates showed an efficacy comparable to a polyvalent commercial FMDV vaccine and protected 100% the animals from challenge with parental virus. The single and double marked-FMDV vaccine candidates used in conjunction with a cELISA provide a suitable target for DIVA companion tests.
摘要翻译：我们生成了新型分子标记的FMDV A24LL3DYR和A24LL3BPVKV3DYR疫苗候选物。突变体病毒包含导致体内减毒的前导编码区（LL）的缺失和引入病毒非结构3Dpol和3B蛋白之一或两者的阴性抗原标记。在3Dpol蛋白中将突变引入跨越H27N31的FMDV A24Cruzeiro的MAb F32-44表位，得到B型牛鼻炎病毒（BRV-2，Y27R31）的同源氨基酸序列。 3B中的突变包括3B1缺失和3B2突变（RQKP-> PVKV，在BRV-2中发现），其消除与MAb F8B的反应性。这些减毒标记病毒为口蹄疫疫苗生产提供了安全的替代方案。疫苗平台包括独特的限制性内切核酸酶位点，可以方便地交换不同FMDV亚型和血清型的衣壳蛋白。生产嵌合病毒以包含远离相关类型A / Turkey / 06或亚洲型FMDV：Asia1-A24LL3BPVKV3DYR和A / Turkey / 06 -A24LL3BPVKV3DYR的衣壳。 A24LL3DYR和A24LL3BPVKV3DYR突变体病毒在牛中没有产生FMD的迹象，也没有产生毒性病毒的脱落。没有观察到疾病或发烧的临床症状，并且在用活A24LL3DYR或嵌合A-Turkey / 06-A24LL3BPVKV3DYR或Asia1-A24LL3BPVKV3DYR病毒接种的猪中未检测到接触动物的传播。用化学灭活的A24LL3DYR和A24LL3BPVKV3DYRvaccine候选物免疫的牛显示出与多价商业FMDV疫苗相当的功效，并保护100％的动物免受亲代病毒攻击。与cELISA一起使用的单和双标记FMDV疫苗候选者为DIVA伴侣测试提供了合适的目标。

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