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1. 发明申请

WO2017132547A1 PERSONALIZED DELIVERY VECTOR-BASED IMMUNOTHERAPY AND USES THEREOF 审中-公开
标题翻译：个性化递送基于传播的免疫疗法及其应用
公开(公告)号：WO2017132547A1
公开(公告)日：2017-08-03
申请号：PCT/US2017/015403
申请日：2017-01-27
申请人： ADVAXIS, INC.
发明人： PETIT, Robert , PERRY, Kyle , PRINCIOTTA, Michael F.
IPC分类号： C12N15/74 , C12N15/66 , C07K5/10 , C07K14/705 , A61K35/74 , A61K39/00 , A61K48/00
CPC分类号： A61K35/74 , A01K2267/0331 , A61K38/1709 , A61K39/0011 , A61K47/64 , A61K47/646 , A61K2039/522 , A61K2039/523 , A61K2039/6068 , C07K5/10 , C07K14/47 , C07K14/705 , C07K19/00
摘要： Disclosed herein is a personalized immunotherapy composition for a subject having a disease or condition, including therapeutic vaccine delivery vectors and methods of making the same comprising gene expression constructs expressing frameshift-mutation-derived peptides associated with one or more neo-epitopes encoded by nucleic acid sequences comprising at least one frameshift mutation, wherein the frameshift mutation is specific to a subject's cancer or unhealthy tissue. A delivery vector of this disclosure includes bacterial vectors; or viral vectors, or peptide vaccine vectors; or DNA vaccine vectors including Listeria bacterial vectors comprising one or more fusion proteins comprising one or more frameshift-mutation-derived peptides comprising one or more neo-epitopes present in disease-bearing biological samples obtained from the subject. Disclosed are also methods of using these compositions for inducing an immune response against a disease or condition, including a tumor or cancer, or an infection in the subject.
摘要翻译：本文公开了用于患有疾病或病症的受试者的个体化免疫治疗组合物，包括治疗性疫苗递送载体及其制备方法，所述方法包括表达移码突变衍生肽与基因表达构建体相关的基因表达构建体，由包含至少一个移码突变的核酸序列编码的更多新表位，其中移码突变对个体的癌症或不健康组织特异。本公开的递送载体包括细菌载体; 或病毒载体或肽疫苗载体; 或DNA疫苗载体，包括含有一种或多种融合蛋白的李斯特菌细菌载体，所述融合蛋白包含一种或多种移码突变衍生的肽，所述肽包含存在于患有受试者的疾病的生物样品中存在的一种或多种新表位。还公开了使用这些组合物诱导抗疾病或病症（包括肿瘤或癌症）或受试者感染的免疫应答的方法。

2. 发明申请

WO2019094607A2 IMMUNOGENIC HETEROCLITIC PEPTIDES FROM CANCER-ASSOCIATED PROTEINS AND METHODS OF USE THEREOF 审中-公开
公开(公告)号：WO2019094607A2
公开(公告)日：2019-05-16
申请号：PCT/US2018/059849
申请日：2018-11-08
申请人： ADVAXIS, INC.
发明人： PETIT, Robert , PRINCIOTTA, Michael F. , CODER, Brandon , BALLI, David
摘要： Provided herein are tumor-associated antigen peptides comprising heteroclitic mutations and fusion polypeptides comprising such heteroclitic peptide. Also provided are nucleic acids encoding such peptides and fusion polypeptides, recombinant bacteria or Listeria strains comprising such peptides, fusion polypeptides, or nucleic acids, and cell banks comprising such recombinant bacteria or Listeria strains. Also provided herein are methods of generating such peptides, fusion polypeptides, nucleic acids, and recombinant bacteria or Listeria strains. Also provided are immunogenic compositions, pharmaceutical compositions, and vaccines comprising such peptides, fusion polypeptides, nucleic acids, or recombinant bacteria or Listeria strains. Also provided are methods of inducing an anti-tumor-associated-antigen immune response in a subject, methods of inducing an anti-tumor or anti-cancer immune response in a subject, methods of treating a tumor or cancer in a subject, methods of preventing a tumor or cancer in a subject, and methods of protecting a subject against a tumor or cancer using such peptides, recombinant fusion polypeptides, nucleic acids, recombinant bacteria or Listeria strains, immunogenic compositions, pharmaceutical compositions, or vaccines.

3. 发明申请

WO2016154412A2 COMBINATION OF A PD-1 ANTAGONIST AND A LISTERIA BASED VACCINE FOR TREATING PANCREATIC CANCER 审中-公开
标题翻译： PD-1拮抗剂和基于LISTERIA的疫苗的组合用于治疗胰腺癌
公开(公告)号：WO2016154412A2
公开(公告)日：2016-09-29
申请号：PCT/US2016/023969
申请日：2016-03-24
申请人： THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA , ADVAXIS, INC.
发明人： BEATTY, Gregory L. , KNOBLOCK, Dawson , PETIT, Robert , PRINCIOTTA, Michael F. , WALLECHA, Anu
IPC分类号： A61K39/12 , A61K39/395 , A61K48/00 , A61P35/00
CPC分类号： A61K39/12 , A61K39/00 , A61K39/395 , A61K48/00 , A61K2039/55544 , A61K2039/585
摘要： The present invention relates to combination therapies useful for the treatment of cancer. In particular, the invention relates to the treatment of pancreatic cancer using an antagonist of a Programmed Death 1 protein (PD-1) in combination with a live attenuated recombinant Listeria strain comprising a fusion protein of a PEST sequence-containing polypeptide fused to a tumor-associated antigen.
摘要翻译：本发明涉及可用于治疗癌症的组合疗法。特别地，本发明涉及使用程序性死亡1蛋白（PD-1）的拮抗剂与活的减毒重组利斯特氏菌菌株联合治疗胰腺癌，其包含与肿瘤融合的含有PEST序列的多肽的融合蛋白相关抗原。

4. 发明申请

WO2016141121A1 LISTERIA-BASED COMPOSITIONS COMPRISING A PEPTIDE MINIGENE EXPRESSION SYSTEM AND METHODS OF USE THEREOF 审中-公开
标题翻译：基于LISTERIA的组合物包含肽微管子表达系统及其使用方法
公开(公告)号：WO2016141121A1
公开(公告)日：2016-09-09
申请号：PCT/US2016/020571
申请日：2016-03-03
申请人： ADVAXIS, INC.
发明人： PETIT, Robert , PRINCIOTTA, Michael F.
IPC分类号： C12N1/21 , C12N15/74 , C12N9/10 , C12N9/90 , C07K14/195 , A61K35/74 , A61P35/00
CPC分类号： A61K35/74 , A61K38/00 , C07K14/00 , C07K2319/036 , C12N15/74 , C12N2710/20034 , C12P21/02
摘要： This disclosure provides compositions, including Listeria delivery vectors comprising minigene expression constructs, and methods of using the same for inducing an immune response against an antigen-expressing tumor and for treating the same, and vaccinating against the same in subjects bearing the tumors.
摘要翻译：本公开内容提供了组合物，包括包含小基因表达构建体的利斯特氏菌递送载体，以及使用该组合物来诱导针对抗原表达肿瘤的免疫应答并用于治疗其的方法，并在携带肿瘤的受试者中接种疫苗。

5. 发明申请

WO2018102585A1 PERSONALIZED IMMUNOTHERAPY IN COMBINATION WITH IMMUNOTHERAPY TARGETING RECURRENT CANCER MUTATIONS 审中-公开
公开(公告)号：WO2018102585A1
公开(公告)日：2018-06-07
申请号：PCT/US2017/064016
申请日：2017-11-30
申请人： ADVAXIS, INC. , PETIT, Robert , PERRY, Kyle , PRINCIOTTA, Michael F. , O'CONNOR, Daniel J. , CODER, Brandon , BALLI, David
发明人： PETIT, Robert , PERRY, Kyle , PRINCIOTTA, Michael F. , O'CONNOR, Daniel J. , CODER, Brandon , BALLI, David
IPC分类号： A61K35/74 , A61K39/00 , A61K48/00 , C12N15/74 , C07K14/47
CPC分类号： A61K39/0011 , A61K35/74 , A61K2039/523 , A61K2039/545 , A61K2039/55544 , A61K2039/55594 , A61K2039/64 , A61K2039/645 , C07K14/47 , C07K14/4746 , C07K14/4748 , C07K14/71
摘要： Provided herein are systems comprising recurrent cancer mutation immunotherapy compositions and personalized neoepitope immunotherapy compositions. Also provided are recurrent cancer mutation immunotherapy compositions comprising a recombinant Listeria strain comprising a nucleic acid comprising a nucleic acid comprising an open reading frame encoding a recombinant fusion polypeptide comprising one or more antigenic peptides (e.g., fused to a PEST-containing peptide) from cancer-associated proteins. The antigenic peptides can comprise one or more or all of an antigenic peptide comprising a recurrent cancer mutation, an antigenic peptide comprising a heteroclitic mutation, or an antigenic peptide fused to a ubiquitin protein. Also provided are recurrent cancer mutation immunotherapy compositions comprising a recombinant Listeria strain comprising a nucleic acid comprising an open reading frame encoding a fusion polypeptide, wherein the fusion polypeptide comprises a PEST-containing peptide fused to two or more antigenic peptides, wherein each of the antigenic peptides comprises a recurrent cancer mutation, and wherein at least two of the antigenic peptides comprise different recurrent cancer mutations and are fragments of the same cancer-associated protein. Also provided are personalized immunotherapy compositions comprising a recombinant Listeria strain comprising a nucleic acid comprising an open reading frame encoding a fusion polypeptide, wherein the fusion polypeptide comprises a PEST-containing peptide fused to one or more antigenic peptides, wherein each of the antigenic peptides comprises a cancer-specific neoepitope comprising a cancer-specific mutation found in a cancer sample from a subject but not in a healthy biological sample from the subject. Also provided are recombinant fusion polypeptides, nucleic acids encoding fusion polypeptides, and methods of generating such compositions. Also provided are methods of inducing an anti-tumor-associated-antigen immune response in a subject, methods of inducing an anti-tumor or anti-cancer immune response in a subject, methods of treating a tumor or cancer in a subject, methods of preventing a tumor or cancer in a subject, and methods of protecting a subject against a tumor or cancer using such immunotherapy compositions, recombinant fusion polypeptides, nucleic acids, or recombinant bacteria or Listeria strains.

6. 发明申请

WO2016191545A1 PERSONALIZED DELIVERY VECTOR-BASED IMMUNOTHERAPY AND USES THEREOF 审中-公开
标题翻译：个性化交付矢量的免疫及其用途
公开(公告)号：WO2016191545A1
公开(公告)日：2016-12-01
申请号：PCT/US2016/034301
申请日：2016-05-26
申请人： ADVAXIS, INC.
发明人： PETIT, Robert , PERRY, Kyle , PRINCIOTTA, Michael F. , O'CONNOR, Daniel J.
IPC分类号： A61K48/00 , A61K38/16 , C07K14/195 , C12N15/74
CPC分类号： C07K14/195 , A61K39/0011 , A61K48/00 , A61K2039/523 , C12N15/62 , C12N2710/20034 , Y02A50/491 , Y02A50/492 , Y02A50/51 , Y02A50/53 , Y02A50/54 , Y02A50/55 , Y02A50/58 , Y02A50/60
摘要： This invention provides a system of providing and creating personalized immunotherapeutic compositions for a subject having a disease or condition, including therapeutic immunotherapy delivery vectors and methods of making the same comprising gene expression constructs expressing peptides associated with one or more neo-epitopes or peptides containing mutations that are specific to a subject's cancer or unhealthy tissue. A delivery vector of this invention includes bacterial vectors including Listeria bacterial vectors; or viral vectors, peptide immunotherapy vectors; or DNA immunotherapy vectors, comprising one or more fusion proteins comprising one or more peptides comprising one or more neo-epitopes present in disease-bearing biological samples obtained from the subject. This invention also provides methods of using the same for inducing an immune response against a disease or condition, including a tumor or cancer, or an infection, or an autoimmune disease or an organ transplant rejection in the subject.
摘要翻译：本发明提供了一种为具有疾病或病症的受试者提供和创造个性化的免疫治疗组合物的系统，包括治疗性免疫治疗递送载体及其制备方法，其包含表达与一个或多个新表位或肽相关的肽的基因表达构建体，其含有突变这是特定于受试者的癌症或不健康的组织。本发明的递送载体包括细菌载体，包括李斯特菌属细菌载体; 或病毒载体，肽免疫治疗载体; 或DNA免疫治疗载体，其包含一种或多种包含一种或多种包含存在于从受试者获得的患有疾病的生物样品中的新表位的肽的融合蛋白。本发明还提供了使用其来诱导针对受试者中包括肿瘤或癌症，感染或自身免疫疾病或器官移植排斥的疾病或病症的免疫应答的方法。

7. 发明申请

WO2018102584A1 IMMUNOGENIC COMPOSITIONS TARGETING RECURRENT CANCER MUTATIONS AND METHODS OF USE THEREOF 审中-公开
公开(公告)号：WO2018102584A1
公开(公告)日：2018-06-07
申请号：PCT/US2017/064015
申请日：2017-11-30
申请人： ADVAXIS, INC. , PETIT, Robert , PRINCIOTTA, Michael F. , CODER, Brandon , BALLI, David
发明人： PETIT, Robert , PRINCIOTTA, Michael F. , CODER, Brandon , BALLI, David
IPC分类号： C12N15/74 , C07K14/47 , A61K35/74 , A61K39/00 , A61K48/00
摘要： Provided herein are recombinant fusion polypeptides comprising one or more antigenic peptides (e.g., fused to a PEST-containing peptide) from cancer-associated proteins. The antigenic peptides can comprise one or more or all of an antigenic peptide comprising a recurrent cancer mutation, an antigenic peptide comprising a heteroclitic mutation, or an antigenic peptide fused to a ubiquitin protein. For example, provided herein are recombinant fusion polypeptides comprising two or more antigenic peptides (e.g., fused to a PEST-containing peptide), wherein each antigenic peptide comprises a recurrent cancer mutation, and wherein at least two of the antigenic peptides are fragments of the same cancer-associated protein. Also provided are nucleic acids encoding such fusion polypeptides, recombinant bacteria or Listeria strains comprising such fusion polypeptides or such nucleic acids, and cell banks comprising such recombinant bacteria or Listeria strains. Also provided herein are methods of generating such fusion polypeptides, such nucleic acids, and such recombinant bacteria or Listeria strains. Also provided are immunogenic compositions, pharmaceutical compositions, and vaccines comprising such fusion polypeptides, such nucleic acids, or such recombinant bacteria or Listeria strains. Also provided are methods of inducing an anti-tumor-associated-antigen immune response in a subject, methods of inducing an anti-tumor or anti-cancer immune response in a subject, methods of treating a tumor or cancer in a subject, methods of preventing a tumor or cancer in a subject, and methods of protecting a subject against a tumor or cancer using such recombinant fusion polypeptides, nucleic acids, recombinant bacteria or Listeria strains, immunogenic compositions, pharmaceutical compositions, or vaccines.

8. 发明申请

WO2017048850A1 LISTERIA-BASED IMMUNOGENIC COMPOSITIONS AND METHODS OF USE THEREOF IN CANCER PREVENTION AND TREATMENT 审中-公开
标题翻译：基于LISTERIA的免疫组织化学及其在癌症预防和治疗中的使用方法
公开(公告)号：WO2017048850A1
公开(公告)日：2017-03-23
申请号：PCT/US2016/051748
申请日：2016-09-14
申请人： ADVAXIS, INC.
发明人： PETIT, Robert , PRINCIOTTA, Michael F. , PERRY, Kyle
IPC分类号： C12N15/74 , C07K14/195 , C07K14/47 , A61K39/02 , A61K39/39 , A61K39/00
CPC分类号： A61K39/00 , A61K2039/585 , C07K14/195 , C07K14/4747 , C07K14/705 , C07K2319/00 , C07K2319/03 , C12N9/6424 , C12N9/6445 , C12N15/74
摘要： Disclosed herein are recombinant Listeria strains comprising nucleotides encoding two or more heterologous antigens each fused to a truncated LLO, an N-terminal ActA or a PEST-sequence, methods of preparing same, and methods of inducing an immune response, and treating, inhibiting, or suppressing cancer or tumors comprising administering same.
摘要翻译：本文公开了包含编码两个或更多个异源抗原的核苷酸的重组李斯特菌菌株，其各自与截短的LLO，N末端ActA或PEST序列融合，其制备方法，以及诱导免疫应答的方法，以及治疗，或抑制癌症或肿瘤，包括施用它们。

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