公开(公告)号：US20240350627A1

公开(公告)日：2024-10-24

申请号：US18292586

申请日：2022-07-28

申请人： Takeda Pharmaceutical Company Limited

发明人： Chihiro Take ,  Akiko Yamaguchi ,  Gary Shapiro

IPC分类号： A61K39/00 ,  A61P35/00 ,  C07K14/52 ,  C07K14/54 ,  C07K14/705 ,  C07K14/725 ,  C07K16/30 ,  C12N5/0783

CPC分类号： A61K39/4611 ,  A61K39/4631 ,  A61K39/4635 ,  A61K39/464468 ,  A61P35/00 ,  C07K14/521 ,  C07K14/5418 ,  C07K14/7051 ,  C07K14/70517 ,  C07K14/70578 ,  C07K16/30 ,  C12N5/0636 ,  C07K2317/53 ,  C07K2317/622 ,  C07K2319/02 ,  C07K2319/03 ,  C12N2510/00

摘要： Disclosed herein are isolated nucleic acid molecules comprising a polynucleotide encoding a chimeric antigen receptor (CAR) comprising an antibody that specifically recognizes human mesothelin, a CD8 hinge region, a CD8 transmembrane region, a 4-1BB intracellular region and a CD3ζ intracellular region; a polynucleotide encoding IL-7; and a polynucleotide encoding CCL19. Also disclosed herein include vectors, modified immune cells, and pharmaceutical compositions comprising the nucleic acid molecules and methods of use.

公开(公告)号：US20240189423A1

公开(公告)日：2024-06-13

申请号：US18553447

申请日：2022-03-30

申请人： The Regents of the University of California

发明人： James A. WELLS ,  Katarina PANCE ,  Josef A. GRAMESPACHER ,  Kaan Kumru

IPC分类号： A61K39/00 ,  A61K47/68 ,  A61P35/00 ,  C07K14/475 ,  C07K14/48 ,  C07K14/49 ,  C07K14/495 ,  C07K14/50 ,  C07K14/505 ,  C07K14/51 ,  C07K14/52 ,  C07K14/525 ,  C07K14/53 ,  C07K14/54 ,  C07K14/55 ,  C07K14/56 ,  C07K14/565 ,  C07K14/57 ,  C07K14/575 ,  C07K14/61 ,  C07K14/65 ,  C07K16/28 ,  C12N5/0781

CPC分类号： A61K39/4644 ,  A61K39/4612 ,  A61K39/4633 ,  A61K47/6851 ,  A61P35/00 ,  C07K14/475 ,  C07K14/48 ,  C07K14/49 ,  C07K14/495 ,  C07K14/50 ,  C07K14/505 ,  C07K14/51 ,  C07K14/521 ,  C07K14/525 ,  C07K14/53 ,  C07K14/5403 ,  C07K14/5406 ,  C07K14/5409 ,  C07K14/5412 ,  C07K14/5418 ,  C07K14/5425 ,  C07K14/5431 ,  C07K14/5434 ,  C07K14/5437 ,  C07K14/55 ,  C07K14/56 ,  C07K14/565 ,  C07K14/57 ,  C07K14/575 ,  C07K14/61 ,  C07K14/65 ,  C07K16/2803 ,  C07K16/2887 ,  C12N5/0635 ,  C07K2317/31 ,  C07K2319/30 ,  C12N2510/00

摘要： The present disclosure relates to targeted degradation platform technology. For example, the present disclosure relates to bispecific binding agents for degrading endogenous proteins, whether membrane-associated or soluble, using the lysosome pathway. The disclosure also provides methods useful for producing such agents, nucleic acids encoding same, host cells genetically modified with the nucleic acids, as well as methods for modulating an activity of a cell and/or for the treatment of various disorders.

公开(公告)号：US20240091256A1

公开(公告)日：2024-03-21

申请号：US18488400

申请日：2023-10-17

申请人： Seattle Children's Hospital (dba Seattle Children's Research Institute)

发明人： Courtney Crane ,  Michael C. Jensen ,  Kara White Moyes ,  Nicole Lieberman

IPC分类号： A61K35/15 ,  A61K35/17 ,  C07K14/47 ,  C07K14/52 ,  C07K14/56 ,  C07K14/705 ,  C12N5/0786 ,  C12N9/22

CPC分类号： A61K35/15 ,  A61K35/17 ,  C07K14/47 ,  C07K14/521 ,  C07K14/56 ,  C07K14/70503 ,  C12N5/0645 ,  C12N9/22 ,  C07K2319/00 ,  C12N2510/00 ,  Y02A50/30

摘要： Disclosed are methods of making a genetically modified immune cell for modifying a tumor microenvironment (TME) and methods of modifying a tumor microenvironment (TME). In some embodiments, the method can include delivering a first vector to an immune cell, wherein the first vector comprises a nucleic acid encoding a protein that induces T-cell proliferation, promotes persistence and activation of endogenous or adoptively transferred NK or T cells and/or induces production of an interleukin, an interferon, a PD-1 checkpoint binding protein, HMGB1, MyD88, a cytokine or a chemokine. Methods of modulating the suppression of the immune response in a tumor microenvironment, minimizing the proliferation of tumor and suppressive cells, and increasing the efficiency of an anti-cancer therapy, anti-infection therapy, antibacterial therapy, anti-viral therapy, or anti-tumoral therapy are also provided.

公开(公告)号：US20230414677A1

公开(公告)日：2023-12-28

申请号：US18175409

申请日：2023-02-27

申请人： Sinai Health System

发明人： Andras Nagy ,  Jeffrey Harding ,  Kristina Nagy

IPC分类号： A61K35/545 ,  A61P27/02 ,  A61P7/04 ,  A61P9/10 ,  A61P1/16 ,  A61P3/00 ,  A61P37/06 ,  A61P19/02 ,  A61P3/10 ,  A61P25/16 ,  A61K45/06 ,  C07K14/47 ,  C07K14/52 ,  C07K14/705 ,  C12N5/0735 ,  C12N15/09

CPC分类号： A61K35/545 ,  A61P27/02 ,  A61P7/04 ,  A61P9/10 ,  A61P1/16 ,  A61P3/00 ,  A61P37/06 ,  A61P19/02 ,  A61P3/10 ,  A61P25/16 ,  A61K45/06 ,  C07K14/47 ,  C07K14/521 ,  C07K14/70503 ,  C07K14/70532 ,  C07K14/70575 ,  C12N5/0606 ,  C12N15/09 ,  C12N2510/00

摘要： A cell genetically modified to comprise at least one mechanism for providing a local immunosuppression at a transplant site when transplanted in an allogeneic host is, and methods for making and using the same is provided. The cell comprises a set of transgenes, each transgene encoding a gene product that is cytoplasmic, membrane bound, or local acting, and whose function is one or more of: to mitigate antigen presenting cell activation and function; to mitigate graft attacking leukocyte activity or cytolytic function; to mitigate macrophage cytolytic function and phagocytosis of allograft cells; to induce apoptosis in graft attacking leukocytes; to mitigate local inflammatory proteins; and to protect against leukocyte-mediated apoptosis.

公开(公告)号：US11826384B2

公开(公告)日：2023-11-28

申请号：US16694024

申请日：2019-11-25

申请人： Seattle Children's Hospital

发明人： Courtney Crane ,  Michael C. Jensen ,  Kara White Moyes ,  Nicole Lieberman

IPC分类号： A61K35/15 ,  A61K35/17 ,  C07K14/47 ,  C07K14/56 ,  C12N9/22 ,  C07K14/52 ,  C07K14/705 ,  C12N5/0786

CPC分类号： A61K35/15 ,  A61K35/17 ,  C07K14/47 ,  C07K14/521 ,  C07K14/56 ,  C07K14/70503 ,  C12N5/0645 ,  C12N9/22 ,  C07K2319/00 ,  C12N2510/00 ,  Y02A50/30

摘要： Disclosed are methods of making a genetically modified immune cell for modifying a tumor microenvironment (TME) and methods of modifying a tumor microenvironment (TME). In some embodiments, the method can include delivering a first vector to an immune cell, wherein the first vector comprises a nucleic acid encoding a protein that induces T-cell proliferation, promotes persistence and activation of endogenous or adoptively transferred NK or T cells and/or induces production of an interleukin, an interferon, a PD-1 checkpoint binding protein, HMGB1, MyD88, a cytokine or a chemokine. Methods of modulating the suppression of the immune response in a tumor microenvironment, minimizing the proliferation of tumor and suppressive cells, and increasing the efficiency of an anti-cancer therapy, anti-infection therapy, antibacterial therapy, anti-viral therapy, or anti-tumoral therapy are also provided.

公开(公告)号：US11779612B2

公开(公告)日：2023-10-10

申请号：US16520155

申请日：2019-07-23

申请人： Actym Therapeutics, Inc.

发明人： Christopher D. Thanos ,  Laura Hix Glickman ,  Justin Skoble ,  Alexandre Charles Michel Iannello

IPC分类号： A61K35/74 ,  A61K39/112 ,  C07K14/52 ,  C07K16/24 ,  C12N15/74 ,  A61K45/06 ,  A61P35/00 ,  C07K16/28 ,  C12N1/20 ,  C12R1/42

CPC分类号： A61K35/74 ,  A61K39/0275 ,  A61P35/00 ,  C07K14/521 ,  C07K16/248 ,  C07K16/2818 ,  C07K16/2827 ,  C12N1/205 ,  C12N15/74 ,  A61K45/06 ,  C12R2001/42

摘要： Provided are delivery immunostimulatory bacteria that have enhanced colonization of tumors, the tumor microenvironment and/or tumor-resident immune cells, and enhanced anti-tumor activity. The immunostimulatory bacteria are modified by deletion of genes encoding the flagella or modification of the genes so that functional flagella are not produced, and/or are modified by deletion of pagP or modification of pagP to produce inactive PagP product. As a result, the immunostimulatory bacteria are flagellin− and/or pagP−. The immunostimulatory bacteria optionally have additional genomic modifications so that the bacteria are adenosine or purine auxotrophs. The bacteria optionally are one or more of asd−, purI− and msbB−. The immunostimulatory bacteria, such as Salmonella species, are modified to encode immunostimulatory proteins that confer anti-tumor activity in the tumor microenvironment, and/or are modified so that the bacteria preferentially infect immune cells in the tumor microenvironment or tumor-resident immune cells and/or induce less cell death in immune cells than in other cells. Also provided are methods of inhibiting the growth or reducing the volume of a solid tumor by administering the immunostimulatory bacteria.

公开(公告)号：US20230302128A1

公开(公告)日：2023-09-28

申请号：US18172905

申请日：2023-02-22

申请人： Massachusetts Institute of Technology

发明人： Darrell J. IRVINE ,  Karl Dane Wittrup ,  Tyson Moyer ,  Yash Agarwal

IPC分类号： A61K39/395 ,  A61P35/00 ,  A61K33/08 ,  A61K38/19 ,  A61K38/20 ,  C07K14/52 ,  C07K14/525 ,  C07K14/54 ,  C07K16/28

CPC分类号： A61K39/3955 ,  A61P35/00 ,  A61K33/08 ,  A61K38/191 ,  A61K38/195 ,  A61K38/20 ,  C07K14/521 ,  C07K14/525 ,  C07K14/54 ,  C07K16/2809 ,  C07K2319/30

摘要： The present disclosure provides immunomodulatory fusion proteins-metal hydroxide complexes comprising an immunomodulatory domain adsorbed to a metal hydroxide via ligand exchange. The disclosure also features compositions and methods of using the same, for example, to treat cancer.

公开(公告)号：US20230226122A1

公开(公告)日：2023-07-20

申请号：US17879559

申请日：2022-08-02

申请人： Synlogic Operating Company, Inc.

发明人： Dean Falb ,  Jonathan W. Kotula ,  Vincent M. Isabella ,  Paul F. Miller ,  Suman Machinani ,  Saurabh Saha ,  Adam B. Fisher ,  Yves Millet ,  Ning Li ,  Jose M. Lora

IPC分类号： A61K35/74 ,  C07K14/52 ,  C07K14/525 ,  C07K14/53 ,  C07K14/54 ,  C07K14/57 ,  C07K14/705 ,  C07K16/28 ,  C12N9/26 ,  C12N15/62 ,  C12N15/74

CPC分类号： A61K35/74 ,  C07K14/53 ,  C07K14/57 ,  C07K14/521 ,  C07K14/525 ,  C07K14/5434 ,  C07K14/5443 ,  C07K14/70575 ,  C07K14/70596 ,  C07K16/2818 ,  C12N9/2408 ,  C12N15/62 ,  C12N15/74 ,  A61K33/243 ,  C07K2317/622 ,  C07K2319/21 ,  C12N2840/002 ,  C12Y302/01003 ,  C12Y302/01035

摘要： Genetically programmed microorganisms, such as bacteria or virus, pharmaceutical compositions thereof, and methods of modulating and treating cancers are disclosed.

公开(公告)号：US20230172170A1

公开(公告)日：2023-06-08

申请号：US17920069

申请日：2021-04-20

申请人： Regeneron Pharmaceuticals, Inc.

发明人： Davor FRLETA ,  Naxin TU ,  Justin GRINDLEY

IPC分类号： A01K67/027 ,  C07K14/52 ,  A61K49/00

CPC分类号： A01K67/0278 ,  A61K49/0008 ,  C07K14/521 ,  A01K2207/15 ,  A01K2217/15 ,  A01K2217/072 ,  A01K2227/105 ,  A01K2267/0331

摘要： Disclosed herein are rodents (such as, but not limited to, mice and rats) genetically modified to comprise a humanized Cxcl13 gene. The rodents disclosed herein have been shown to support better engraftment and proliferation of human cells such as chronic lymphocytic leukemic cells. Compositions and methods for making such genetically modified rodents, as well as methods of using such genetically modified rodents for testing candidate therapeutic agents (e.g., candidate anti-cancer drugs), are provided.

公开(公告)号：US20190194690A1

公开(公告)日：2019-06-27

申请号：US16329098

申请日：2017-08-29

申请人： PSIOXUS THERAPEUTICS LIMITED

发明人： Brian Robert CHAMPION ,  Alice Claire Noel BROMLEY ,  Joshua David FREEDMAN ,  Kerry David FISHER ,  Leonard William SEYMOUR

IPC分类号： C12N15/86 ,  C07K16/28 ,  C07K16/30 ,  C07K14/52 ,  A61P35/00 ,  A61K35/761

CPC分类号： C12N15/86 ,  A61K35/761 ,  A61K38/00 ,  A61K39/39558 ,  A61K2039/505 ,  A61K2039/5256 ,  A61K2039/585 ,  A61K2300/00 ,  A61P35/00 ,  C07K14/521 ,  C07K16/2809 ,  C07K16/30 ,  C07K16/40 ,  C07K2317/31 ,  C07K2317/56 ,  C07K2317/622 ,  C07K2317/73 ,  C07K2317/75 ,  C07K2319/92 ,  C12N2710/10332 ,  C12N2710/10343 ,  C12N2830/60 ,  C12N2840/44

摘要： A modified adenovirus, in particular Enadenotucirev (EnAd), armed with a bispecific T cell engager (BiTE™) comprising at least two binding domains, wherein at least one of the domains is specific for a surface antigen on a T-cell of interest. Also provided are a composition, such as a pharmaceutical formulation comprising the virus, use of the virus and virus formulations for treatment, such as in the treatment of cancer. The disclosure also extends to processes for preparing the virus.