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公开(公告)号：US10828356B1
公开(公告)日：2020-11-10
申请号：US16410627
申请日：2019-05-13
摘要： Bacterial strains are provided having at least one of a reduced size, a sialic acid coat, inducibly altered surface antigens, and expression of PD-L1 or CTLA-4 antagonists and/or tryptophanase. The bacteria may have improved serum half-life, increased penetration into tumors, increased tumor targeting and increased antitumor activity. The bacteria are useful for delivery of therapeutic agents that treat of neoplastic diseases including solid tumors and lymphomas.
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公开(公告)号：US10590185B1
公开(公告)日：2020-03-17
申请号：US15600267
申请日：2017-05-19
IPC分类号： A61K38/55 , C07K14/81 , C12N15/113 , C12N15/74 , A61K38/00 , C07K14/245
摘要： A genetically engineered live bacterium which is adapted to selectively replicate in and colonize a selected tissue type within the mammal, and concurrently produce within the selected tissue type at least one protease-sensitive cytotoxic molecule which is degradable by proteases within the selected tissue type, and at least one protease inhibitor peptide to inhibit the proteases within the selected tissue type from proteolytically degrading the protease sensitive cytotoxic molecule. The combination results in higher concentrations of the cytotoxic molecule local to the colonization, while permitting protease degradation of the cytotoxic molecule further away from the colonization.
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公开(公告)号：US10087451B2
公开(公告)日：2018-10-02
申请号：US15131083
申请日：2016-04-18
摘要： A live bacterium, having a DNA construct stabilized against transduction of other bacteria, having a promoter sequence and encoding a fusion peptide, comprising a bacterial secretion peptide portion and a non-bacterial immunogenic polypeptide portion, having a nucleotide sequence coding for the non-bacterial immunogenic polypeptide portion which has at least one codon optimized for bacterial expression. The bacterium has a secretion mechanism which interacts with at least the bacterial secretion peptide portion to cause a secretion of the fusion peptide from the bacterium, and a genetic virulence attenuating mutation. The bacterium is adapted to act as an animal vaccine, to transiently infect a tissue of the animal, and cause an immunity response to the non-bacterial immunogenic polypeptide portion in the animal to a non-bacterial organism associated with the non-bacterial immunogenic polypeptide portion.
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公开(公告)号：US09739773B1
公开(公告)日：2017-08-22
申请号：US14623956
申请日：2015-02-17
IPC分类号： G01N33/53 , G01N33/538 , G01N33/536 , G01N33/563 , G01N33/558 , G01N33/68
CPC分类号： G01N33/558 , G01N33/6854 , G01N2469/20
摘要： A host antigen-specific antibody testing system and method. The a ternary complex of the antigen, a ligand-bound anti-host IgM, and a non-host anti-antigen IgG detector conjugate selectively form a quaternary complex with host antibodies, wherein the host antibodies and IgG compete for the antigen, and the anti-host IgM binds the host antibodies. The quaternary complex is retained by an immobilized IgM ligand binding agent, and any residual ternary complex is retained by a later encountered immobilized anti-non-host IgG. If sufficient host antibodies have a high affinity for the antigen, the complex is detected at the quaternary complex detection region based on the presence of the detector, and if there are insufficient high affinity host antibodies, the ternary complex migrates past the quaternary complex detection region and is retained and detected at a control region.
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公开(公告)号：US09657085B1
公开(公告)日：2017-05-23
申请号：US14954387
申请日：2015-11-30
IPC分类号： A61K38/55 , C07K14/81 , C07K14/245 , C12N15/74 , C12N15/113 , A61K38/00
CPC分类号： C07K14/81 , A61K35/74 , A61K38/00 , A61K38/164 , A61K38/55 , C07K14/005 , C07K14/245 , C07K2319/50 , C07K2319/55 , C12N9/0071 , C12N9/22 , C12N15/1135 , C12N15/1137 , C12N15/74 , C12N2310/14 , C12N2310/141 , Y02A50/483
摘要： A genetically engineered live bacterium which is adapted to selectively replicate in and colonize a selected tissue type within the mammal, and concurrently produce within the selected tissue type at least one protease-sensitive cytotoxic molecule which is degradable by proteases within the selected tissue type, and at least one protease inhibitor peptide to inhibit the proteases within the selected tissue type from proteolytically degrading the protease sensitive cytotoxic molecule. The combination results in higher concentrations of the cytotoxic molecule local to the colonization, while permitting protease degradation of the cytotoxic molecule further away from the colonization.
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6.发明授权Bacteria carrying bacteriophage and protease inhibitors for the treatment of disorders and methods of treatment 有权携带噬菌体和蛋白酶抑制剂的细菌用于治疗疾病和治疗方法公开(公告)号：US09593339B1
公开(公告)日：2017-03-14
申请号：US14180766
申请日：2014-02-14
IPC分类号： A61K35/74 , A61K35/76 , A61K38/00 , A61K39/00 , C12N15/74 , A61K31/7105 , A61K31/713 , A61K38/55 , A61K39/395
CPC分类号： C12N15/746 , A61K31/7105 , A61K31/713 , A61K38/55 , A61K39/39558 , A61K2039/505 , C07K16/241 , C07K2317/76 , Y02A50/419 , A61K2300/00
摘要： The present invention uses co-expression of protease inhibitors and protease sensitive therapeutic agents including phage and phagemids delivering peptides, therapeutic antibodies, DNA and RNA-based therapeutics that results in treating inflammation of a variety of disorders including psoriasis, atopic dermatitis and inflammatory bowel disease. The invention also provides bacteria that inhibit the growth of intestinal parasites such as worms, and deliver siRNA or miRNA that have specific anti-parasitic effects that results in the reduction or elimination of the parasite.
摘要翻译： 本发明使用蛋白酶抑制剂和蛋白酶敏感性治疗剂的共表达，包括噬菌体和噬菌粒递送肽，治疗性抗体，基于DNA和RNA的治疗剂，其导致治疗各种疾病的炎症，包括牛皮癣，特应性皮炎和炎症性肠病 。 本发明还提供抑制肠寄生虫如蠕虫的生长的细菌，并且递送具有特异性抗寄生效应的siRNA或miRNA，导致寄生虫的减少或消除。
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7.发明授权Immunization and/or treatment of parasites and infectious agents by live bacteria 有权用活细菌免疫和/或治疗寄生虫和感染因子公开(公告)号：US09486513B1
公开(公告)日：2016-11-08
申请号：US14321315
申请日：2014-07-01
CPC分类号： A61K39/07 , A61K35/74 , A61K39/0208 , A61K39/12 , A61K2039/522 , A61K2039/523 , A61K2039/542 , C07K14/81 , C12N15/74 , C12N2760/16134
摘要： Chimeric proteins are expressed, secreted or released by a bacterium to immunize against or treat a parasite, infectious disease or malignancy. The delivery vector may also be attenuated, non-pathogenic, low pathogenic, or a probiotic bacterium. The chimeric proteins include chimeras of, e.g., phage coat and/or colicin proteins, bacterial toxins and/or enzymes, autotransporter peptides, lytic peptides, multimerization domains, and/or membrane transducing (ferry) peptides. The active portion of the immunogenic chimeric proteins can include antigens against a wide range of parasites and infectious agents, cancers, Alzheimer's and Huntington's diseases, and have enhanced activity when secreted or released by the bacteria, and/or have direct anti-parasite or infectious agent activity. The activity of the secreted proteins is further increased by co-expression of a protease inhibitor that prevents degradation of the effector peptides. Addition of an antibody binding or antibody-degrading protein further prevents the premature elimination of the vector and enhances the immune response.
摘要翻译： 嵌合蛋白由细菌表达，分泌或释放以免疫或治疗寄生虫，感染性疾病或恶性肿瘤。 递送载体也可以是减毒，非致病性，低致病性或益生菌。 嵌合蛋白包括例如噬菌体外壳和/或大肠杆菌素蛋白，细菌毒素和/或酶，自动转运肽，裂解肽，多聚化结构域和/或膜转导（转运）肽的嵌合体。 免疫原性嵌合蛋白的活性部分可以包括针对广泛范围的寄生虫和感染因子，癌症，阿尔茨海默病和亨廷顿疾病的抗原，并且在细菌分泌或释放时具有增强的活性，和/或具有直接的抗寄生虫或感染性 代理活动。 分泌的蛋白质的活性通过蛋白酶抑制剂的共表达进一步增加，其阻止效应肽的降解。 抗体结合或抗体降解蛋白的添加进一步阻止载体的过早消除并增强免疫应答。
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8.发明授权Live bacterial vaccines resistant to carbon dioxide (CO2), acidic pH and/or osmolarity for viral infection prophylaxis or treatment 有权耐二氧化碳（CO2），酸性pH和/或渗透压用于病毒感染预防或治疗的活细菌疫苗公开(公告)号：US09421252B2
公开(公告)日：2016-08-23
申请号：US14172272
申请日：2014-02-04
IPC分类号： A61K39/00 , A61K39/02 , A61K39/38 , A61K39/145 , C12N1/20 , C12N1/36 , C12N9/10 , C12N7/00 , A61K39/12
CPC分类号： A61K39/145 , A61K39/12 , A61K2039/522 , A61K2039/523 , C12N1/20 , C12N1/36 , C12N7/00 , C12N9/1025 , C12N2510/00 , C12N2760/16034 , C12N2760/16134
摘要： Gram-negative bacterial mutants resistant stress conditions, including CO2, acid pH, and high osmolarity are provided, having reduced TNF-α induction having a msbB mutation, that are rendered stress-resistant by a mutation in the zwf gene. A method for prophylaxis or treatment of a virally induced disease in a subject comprising administering to said subject attenuated stress-resistant gram-negative bacterial mutants, is also provided, along with Methods for prophylaxis or treatment of a virally induced disease in a subject comprise administering to said subject one or more stress-resistant gram-negative bacterial mutants as vectors for the delivery of one or more therapeutic molecules. The methods provide efficient delivery of therapeutic molecules by stress-resistant gram-negative bacterial mutants engineered to express said therapeutic molecules.
摘要翻译： 提供革兰氏阴性细菌突变体抗性应激条件，包括CO 2，酸性pH和高渗透压，具有降低的具有msbB突变的TNF-α诱导，其通过zwf基因的突变而产生抗应激性。 还提供了用于预防或治疗受试者中的病毒诱导的疾病的方法，包括对所述受试者施用减毒抗性革兰氏阴性细菌突变体，以及在受试者中预防或治疗病毒诱导的疾病的方法包括施用 所述受试者一种或多种抗应激革兰氏阴性细菌突变体作为递送一种或多种治疗分子的载体。 所述方法通过工程化以表达所述治疗分子的抗应激性革兰氏阴性细菌突变体提供治疗性分子的有效递送。
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公开(公告)号：US20160222393A1
公开(公告)日：2016-08-04
申请号：US15131083
申请日：2016-04-18
IPC分类号： C12N15/74
CPC分类号： C12N15/74 , A61K39/12 , A61K39/145 , A61K2039/522 , A61K2039/523 , A61K2039/542 , A61K2039/552 , C12N1/36 , C12N9/2402 , C12N2760/16134 , C12Y302/01018
摘要： A live bacterium, having a DNA construct stabilized against transduction of other bacteria, having a promoter sequence and encoding a fusion peptide, comprising a bacterial secretion peptide portion and a non-bacterial immunogenic polypeptide portion, having a nucleotide sequence coding for the non-bacterial immunogenic polypeptide portion which has at least one codon optimized for bacterial expression. The bacterium has a secretion mechanism which interacts with at least the bacterial secretion peptide portion to cause a secretion of the fusion peptide from the bacterium, and a genetic virulence attenuating mutation. The bacterium is adapted to act as an animal vaccine, to transiently infect a tissue of the animal, and cause an immunity response to the non-bacterial immunogenic polypeptide portion in the animal to a non-bacterial organism associated with the non-bacterial immunogenic polypeptide portion.
摘要翻译： 具有稳定的其他细菌转导的DNA构建体的活细菌，具有编码非细菌的核苷酸序列的具有启动子序列并编码融合肽的细菌分泌肽部分和非细菌免疫原性多肽部分 具有至少一个针对细菌表达优化的密码子的免疫原性多肽部分。 细菌具有与至少细菌分泌肽部分相互作用以引起细菌融合肽分泌的分泌机制，以及遗传毒力减弱突变。 该细菌适于充当动物疫苗，以瞬时感染动物的组织，并且对动物中的非细菌免疫原性多肽部分产生与非细菌免疫原性多肽相关的非细菌生物的免疫应答 一部分。
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公开(公告)号：US09404148B2
公开(公告)日：2016-08-02
申请号：US12738977
申请日：2008-10-21
申请人： Nittaya Gale , Paul Debenham , David John French , Rebecca Howard , David Gordon McDowell , Tom Brown
发明人： Nittaya Gale , Paul Debenham , David John French , Rebecca Howard , David Gordon McDowell , Tom Brown
CPC分类号： C12Q1/6827 , C12Q2527/107 , C12Q2525/186 , C12Q2525/151
摘要： A method for determining the number of tandem repeats in a target polynucleotide, the method comprising (a) providing a sample containing the target polynucleotide, wherein one or more of the tandem repeats in the target polynucleotide is in single stranded form, (b) hybridizing a labelled probe oligonucleotide to the single stranded portion of the target polynucleotide, wherein the probe oligonucleotide is complementary to at least one of the tandem repeats, and at least 5 nucleotides of the probe oligonucleotide are complementary to the tandem repeats, in the single stranded portion of the target polynucleotide, and (c) determining the number of tandem repeats in the target polynucleotide based on the hybridization of the probe oligonucleotide to the single stranded portion of the target polynucleotide.
摘要翻译： 一种用于确定靶多核苷酸中的串联重复数目的方法，所述方法包括（a）提供含有靶多核苷酸的样品，其中靶多核苷酸中的一个或多个串联重复单位为单链形式，（b）杂交 对靶多核苷酸的单链部分的标记探针寡核苷酸，其中所述探针寡核苷酸与至少一个串联重复序列互补，并且探针寡核苷酸的至少5个核苷酸与串联重复序列互补，在单链部分 ，和（c）基于探针寡核苷酸与靶多核苷酸的单链部分的杂交来确定靶多核苷酸中串联重复序列的数目。
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