公开(公告)号：WO2010033798A3

公开(公告)日：2010-03-25

申请号：PCT/US2009/057470

申请日：2009-09-18

Applicant: AVIEX TECHNOLOGIES LLC ,  BERMUDES, David

Inventor： BERMUDES, David

IPC: C12N1/21 ,  C12N15/31 ,  A61K39/112 ,  C12R1/42

Abstract: The present invention relates to gram-negative bacterial mutants resistant to one or more stress conditions, e.g., CO2, acid pH, and high osmolarity. Gram-negative bacterial mutants with reduced TNF-alpha induction having a lipid biosynthesis gene mutation, including, but not limited to msbB, are rendered stress-resistant by a zwf mutation. The stress-resistant gram-negative bacterial mutants are preferably attenuated, and may be used for prophylaxis or treatment of a virally induced disease by administering stress-resistant gram-negative bacterial mutants. Methods for prophylaxis or treatment of a virally induced disease in a subject are provided comprising 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 of the invention provide more efficient delivery of therapeutic molecules by stress-resistant gram-negative bacterial mutants engineered to express said therapeutic molecules.

公开(公告)号：WO0114579A9

公开(公告)日：2002-09-19

申请号：PCT/US0023243

申请日：2000-08-24

Applicant: VION PHARMACEUTICALS INC ,  BERMUDES DAVID G ,  KING IVAN C ,  CLAIRMONT CAROLINE A

Inventor： BERMUDES DAVID G ,  KING IVAN C ,  CLAIRMONT CAROLINE A

IPC: A61K48/00 ,  C12N1/21 ,  A61K39/02 ,  A61K39/112 ,  C07H21/04 ,  C12N1/00 ,  C12N1/20 ,  C12N15/00 ,  C12P21/04 ,  C12P21/06 ,  G01N33/53

CPC classification number: A61K48/00

Abstract: The present application generally discloses delivery of an agent which can be therapeutic or prophylactic and, more particularly, the preparation and use of attenuated bacteria, such as Salmonella , containing a bacteriophage in which the genome of the bacteriophage has been modified to encode for a gene product of interest, e.g., an antigen or an anti-tumor protein. The bacteria functions as a vector for delivering the bacteriophage encoded gene product of interest to an appropriate site of action, e.g., the site of a solid tumor.

Abstract translation: 本申请通常公开了可以是治疗性或预防性的药剂的递送，更具体地说，包含噬菌体的减毒细菌（例如沙门氏菌）的制备和使用，其中噬菌体的基因组已被修饰为 编码感兴趣的基因产物，例如抗原或抗肿瘤蛋白质。 细菌用作用于将感兴趣的噬菌体编码的基因产物递送至适当的作用位点（例如实体瘤的部位）的载体。

公开(公告)号：WO0114579A2

公开(公告)日：2001-03-01

申请号：PCT/US0023243

申请日：2000-08-24

Applicant: VION PHARMACEUTICALS INC ,  BERMUDES DAVID G ,  KING IVAN C ,  CLAIRMONT CAROLINE A

Inventor： BERMUDES DAVID G ,  KING IVAN C ,  CLAIRMONT CAROLINE A

IPC: A61K48/00 ,  C12N1/21 ,  C12Q

CPC classification number: A61K48/00

Abstract: The present application generally discloses delivery of an agent which can be therapeutic or prophylactic and, more particularly, the preparation and use of attenuated bacteria, such as Salmonella , containing a bacteriophage in which the genome of the bacteriophage has been modified to encode for a gene product of interest, e.g., an antigen or an anti-tumor protein. The bacteria functions as a vector for delivering the bacteriophage encoded gene product of interest to an appropriate site of action, e.g., the site of a solid tumor.

Abstract translation: 本申请通常公开了可以是治疗性或预防性的药剂的递送，更具体地说，包含噬菌体的减毒细菌如沙门氏菌的制备和用途，其中噬菌体的基因组具有 被修饰以编码感兴趣的基因产物，例如抗原或抗肿瘤蛋白。 细菌用作用于将感兴趣的噬菌体编码的基因产物递送至适当的作用位点（例如实体瘤的部位）的载体。

公开(公告)号：WO2010062982A1

公开(公告)日：2010-06-03

申请号：PCT/US2009/065970

申请日：2009-11-25

Applicant: VION PHARMACEUTICALS, INC. ,  KING, Ivan ,  KARSTEN, Verena ,  BERMUDES, David

Inventor： KING, Ivan ,  KARSTEN, Verena ,  BERMUDES, David

IPC: G01N33/569

CPC classification number: C07K14/255 ,  A61K2039/522 ,  C12R1/42 ,  Y02A50/484

Abstract: The present invention discloses CO 2 resistant msbB mutant Salmonella comprising a mutation of a gene encoding an enzyme in the pentose-phosphate pathway. In one embodiment, the mutation is in the zwf gene encoding glucose-6-dehydrogenase. The invention also discloses a method of using the CO 2 resistant msbB mutant Salmonella to inhibit the growth of or reducing the volume of a solid tumor.

Abstract translation: 本发明公开了包含在戊糖磷酸途径中编码酶的基因的突变的耐CO 2抗性msbB突变沙门氏菌。 在一个实施方案中，突变位于编码葡萄糖-6-脱氢酶的zwf基因中。 本发明还公开了一种使用耐CO 2抗性的msbB突变体沙门氏菌抑制实体瘤体积的生长或减少的方法。

公开(公告)号：WO2010043050A1

公开(公告)日：2010-04-22

申请号：PCT/CA2009/001483

申请日：2009-10-16

Applicant: CELATOR PHARMACEUTICALS CORPORATION ,  TARDI, Paul ,  MAYER, Lawrence ,  BERMUDES, David

Inventor： TARDI, Paul ,  MAYER, Lawrence ,  BERMUDES, David

IPC: A61K31/4745 ,  A61K31/496 ,  A61K31/513 ,  A61K31/7072 ,  A61K39/395 ,  A61K9/127 ,  A61P35/00

CPC classification number: A61K9/127 ,  A61K31/4745 ,  A61K31/496 ,  A61K31/513 ,  A61K31/7072 ,  A61K39/39558 ,  A61K2300/00

Abstract: Compositions which comprise a liposomal water-soluble camptothecin and optionally a liposomal fluoropyrimidine in combination with a vascular epithelial growth factor (VEGF) inhibitor such as cetuximab or an epidermal growth factor receptor (EGFR) inhibitor such as bevacizumab are useful in achieving enhanced therapeutic effects for the treatment of cancer.

Abstract translation: 包含脂质体水溶性喜树碱和任选的脂质体氟嘧啶与血管上皮生长因子（VEGF）抑制剂如西妥昔单抗或表皮生长因子受体（EGFR）抑制剂如贝伐单抗联合的组合物可用于实现增强的治疗效果 治疗癌症。

公开(公告)号：WO2001014579A3

公开(公告)日：2001-03-01

申请号：PCT/US2000/023243

申请日：2000-08-24

Applicant: VION PHARMACEUTICALS, INC. ,  BERMUDES, David, G. ,  KING, Ivan, C. ,  CLAIRMONT, Caroline, A.

Inventor： BERMUDES, David, G. ,  KING, Ivan, C. ,  CLAIRMONT, Caroline, A.

IPC: A61K39/02

Abstract: The present application generally discloses delivery of an agent which can be therapeutic or prophylactic and, more particularly, the preparation and use of attenuated bacteria, such as Salmonella , containing a bacteriophage in which the genome of the bacteriophage has been modified to encode for a gene product of interest, e.g., an antigen or an anti-tumor protein. The bacteria functions as a vector for delivering the bacteriophage encoded gene product of interest to an appropriate site of action, e.g., the site of a solid tumor.

公开(公告)号：WO2010033798A2

公开(公告)日：2010-03-25

申请号：PCT/US2009057470

申请日：2009-09-18

Applicant: AVIEX TECHNOLOGIES LLC ,  BERMUDES DAVID

Inventor： BERMUDES DAVID

IPC: C12N1/21 ,  A61K39/112 ,  C12N15/31 ,  C12R1/42

CPC classification number: A61K39/145 ,  A61K39/12 ,  A61K2039/522 ,  A61K2039/523 ,  C12N1/20 ,  C12N1/36 ,  C12N7/00 ,  C12N9/1025 ,  C12N2510/00 ,  C12N2760/16034 ,  C12N2760/16134

Abstract: The present invention relates to gram-negative bacterial mutants resistant to one or more stress conditions, e.g., CO2, acid pH, and high osmolarity. Gram-negative bacterial mutants with reduced TNF-alpha induction having a lipid biosynthesis gene mutation, including, but not limited to msbB, are rendered stress-resistant by a zwf mutation. The stress-resistant gram-negative bacterial mutants are preferably attenuated, and may be used for prophylaxis or treatment of a virally induced disease by administering stress-resistant gram-negative bacterial mutants. Methods for prophylaxis or treatment of a virally induced disease in a subject are provided comprising 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 of the invention provide more efficient delivery of therapeutic molecules by stress-resistant gram-negative bacterial mutants engineered to express said therapeutic molecules.

Abstract translation: 本发明涉及对一种或多种胁迫条件（例如CO 2，酸性pH和高渗透压浓度）具有抗性的革兰氏阴性细菌突变体。 具有脂质生物合成基因突变的具有降低的TNF-α诱导的革兰氏阴性细菌突变体（包括但不限于msbB）通过zwf突变被胁迫抗性。 抗应激性革兰氏阴性细菌突变体优选地被减弱，并且可以通过施用抗应激性革兰氏阴性细菌突变体来用于预防或治疗病毒诱导的疾病。 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，包括向所述受试者施用一种或多种抗应激性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。 本发明的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来提供治疗性分子的更有效的递送。

公开(公告)号：WO0125397A3

公开(公告)日：2002-01-24

申请号：PCT/US0023242

申请日：2000-08-24

Applicant: VION PHARMACEUTICALS INC ,  BERMUDES DAVID G ,  KING IVAN C ,  CLAIRMONT CAROLINE A ,  LIN STANLEY L ,  BELCOURT MICHAEL

Inventor： BERMUDES DAVID G ,  KING IVAN C ,  CLAIRMONT CAROLINE A ,  LIN STANLEY L ,  BELCOURT MICHAEL

IPC: C12N15/09 ,  A61K35/74 ,  A61K38/00 ,  A61K38/16 ,  A61K38/17 ,  A61K38/19 ,  A61K38/20 ,  A61K38/39 ,  A61K38/43 ,  A61K38/46 ,  A61K45/00 ,  A61K45/06 ,  A61K48/00 ,  A61P35/00 ,  A61P43/00 ,  C07K7/06 ,  C07K14/035 ,  C07K14/16 ,  C07K14/225 ,  C07K14/50 ,  C07K19/00 ,  C12N1/21 ,  C12N1/36 ,  C12N15/62 ,  C12N15/74 ,  A61K39/02 ,  A61K39/112

CPC classification number: A61K38/162 ,  A61K35/74 ,  A61K38/164 ,  A61K38/177 ,  A61K38/191 ,  A61K38/195 ,  A61K38/39 ,  A61K38/51 ,  A61K45/06 ,  A61K48/0008 ,  C07K2319/01 ,  C07K2319/035 ,  C12N15/62 ,  C12N15/625 ,  C12N15/74 ,  A61K2300/00

Abstract: The present application discloses the preparation and use of attenuated tumor-targeted bacteria vectors for the delivery of one or more primary effector molecule(s) to the site of a solid tumor. The primary effector molecule(s) of the invention is used in the methods of the invention to treat a solid tumor cancer such as a carcinoma, melanoma, lymphoma, or sarcoma. The invention relates to the surprising discovery that effector molecules, which may be toxic when administered systemically to a host, can be delivered locally to tumors by attenuated tumor-targeted bacteria with reduced toxicity to the host. The application also discloses the delivery of one or more optional effector molecule(s) (termed secondary effector molecules) which may be delivered by the attenuated tumor-targeted bacteria in conjunction with the primary effector molecule(s).

Abstract translation: 本申请公开了减毒的肿瘤靶向细菌载体用于将一种或多种主效应分子递送至实体瘤的位点的制备和用途。 本发明的主效应分子用于本发明的治疗实体肿瘤癌例如癌，黑素瘤，淋巴瘤或肉瘤的方法中。 本发明涉及令​​人惊奇的发现，当向宿主全身施用时，可能具有毒性的效应分子可以通过对宿主毒性降低的减毒肿瘤靶向细菌局部递送至肿瘤。 本申请还公开了一种或多种任选的效应分子（称为次级效应分子）的递送，其可以被减毒的肿瘤靶向细菌与主效应分子结合递送。