公开(公告)号：US20240325340A1

公开(公告)日：2024-10-03

申请号：US18292464

申请日：2022-07-27

申请人： Thomas Jefferson University ,  Texas Heart Institute

发明人： Roger S. Armen ,  Tung Chan ,  Ulrich Rodeck ,  Richard A. F. Dxon ,  Ronald J. Biediger

IPC分类号： A61K31/352 ,  A61K31/165 ,  A61K31/433 ,  C07D311/04

CPC分类号： A61K31/352 ,  A61K31/165 ,  A61K31/433 ,  C07D311/04

摘要： The invention relates in one aspect to compounds, pharmaceutical compositions thereof, and methods using the same for selectively activating either all or a single isoform of Akt. Isoform selective-targeting is necessary for avoiding pathologies driven by concomitantly activated Akt1, Akt2 and/or Akt3.

公开(公告)号：US10414814B2

公开(公告)日：2019-09-17

申请号：US15322438

申请日：2015-07-02

申请人： City of Hope ,  Thomas Jefferson University

发明人： John C. Williams ,  Ulrich Rodeck ,  Kurt Jenkins

IPC分类号： C07K14/82 ,  C07K16/46 ,  C07K14/705 ,  C12N9/64 ,  C07K14/435 ,  C07K19/00 ,  C07K16/28 ,  C07K14/47 ,  C07K14/71

摘要： Provided herein are recombinant masking proteins and recombinant ligand proteins useful in treating cancer, neurodegenerative disease, and cardiovascular disease. The recombinant masking proteins provided herein may, inter alia, be used as non-covalent masks of antagonists of, for example, cellular growth factors (e.g., TNF) or cell surface proteins (e.g., CTLA-4).

公开(公告)号：US11186642B2

公开(公告)日：2021-11-30

申请号：US15439823

申请日：2017-02-22

申请人： City of Hope ,  Thomas Jefferson University

发明人： John C. Williams ,  Ulrich Rodeck ,  Joshua M. Donaldson ,  Csaba Kari

IPC分类号： C07K16/28 ,  C07K16/30 ,  C07K16/32

摘要： In one embodiment, a masked monoclonal antibody (mAb) is provided, the mAb, encoded by a nucleic acid sequence or an amino acid sequence molecule comprising a signal sequence, a masking epitope sequence, a linker sequence that is cleavable by a protease specific to a target tissue; and an antibody or a functional fragment thereof. In another embodiment, a cross-masked mAb heterodimer complex is provided, comprising a first masked mAb, comprising a first signal sequence, a first masking epitope sequence, a first linker that is cleavable by a protease specific to a target tissue, and a first antibody or fragment thereof; and a second masked mAb, comprising a second signal sequence, a second masking epitope sequence, a second linker that is cleavable by a protease specific to a target tissue, and a second antibody or fragment thereof.

公开(公告)号：US20230085485A1

公开(公告)日：2023-03-16

申请号：US17660603

申请日：2022-04-25

申请人： CITY OF HOPE ,  THOMAS JEFFERSON UNIVERSITY

发明人： John C. Williams ,  Cindy Zer ,  Kendra N. Avery ,  Ulrich Rodeck ,  Joshua M. Donaldson ,  Csaba Kari

IPC分类号： A61K47/55 ,  C07K16/28 ,  C07K16/30

摘要： In one embodiment, a masked monoclonal antibody (mAb) is provided, the mAb, encoded by a nucleic acid sequence or an amino acid sequence molecule comprising a signal sequence, a masking epitope sequence, a linker sequence that is cleavable by a protease specific to a target tissue; and an antibody or a functional fragment thereof. In another embodiment, a masked monoclonal antibody (mAb) is provided, which includes a therapeutic mAb and a mask, the mask comprising protein A and protein L attached by a protease cleavable linker.

公开(公告)号：US11311622B2

公开(公告)日：2022-04-26

申请号：US16460957

申请日：2019-07-02

申请人： CITY OF HOPE ,  Thomas Jefferson University

发明人： John C. Williams ,  Cindy Zer ,  Kendra N. Avery ,  Ulrich Rodeck ,  Joshua M. Donaldson ,  Csaba Kari

IPC分类号： A61K47/55 ,  C07K16/28 ,  C07K16/30 ,  C07K16/22

摘要： In one embodiment, a masked monoclonal antibody (mAb) is provided, the mAb, encoded by a nucleic acid sequence or an amino acid sequence molecule comprising a signal sequence, a masking epitope sequence, a linker sequence that is cleavable by a protease specific to a target tissue; and an antibody or a functional fragment thereof. In another embodiment, a masked monoclonal antibody (mAb) is provided, which includes a therapeutic mAb and a mask, the mask comprising protein A and protein L attached by a protease cleavable linker.

公开(公告)号：US10357571B2

公开(公告)日：2019-07-23

申请号：US14949648

申请日：2015-11-23

申请人： City of Hope ,  Thomas Jefferson University

发明人： John C. Williams ,  Cindy Zer ,  Kendra N. Avery ,  Ulrich Rodeck ,  Joshua M. Donaldson ,  Csaba Kari

IPC分类号： C07K16/28 ,  C07K16/30 ,  A61K47/48 ,  A61K47/55

摘要： In one embodiment, a masked monoclonal antibody (mAb) is provided, the mAb, encoded by a nucleic acid sequence or an amino acid sequence molecule comprising a signal sequence, a masking epitope sequence, a linker sequence that is cleavable by a protease specific to a target tissue; and an antibody or a functional fragment thereof. In another embodiment, a masked monoclonal antibody (mAb) is provided, which includes a therapeutic mAb and a mask, the mask comprising protein A and protein L attached by a protease cleavable linker.

公开(公告)号：US10689423B2

公开(公告)日：2020-06-23

申请号：US15543209

申请日：2016-01-13

申请人： City of Hope ,  Thomas Jefferson University and Health System, Innovation Pillar

发明人： John Williams ,  Ulrich Rodeck

IPC分类号： C07K14/705 ,  C07K7/06 ,  C07K5/12 ,  C07K19/00 ,  C07K14/47 ,  A61K47/64 ,  A61K47/65 ,  C12N15/62 ,  A61K38/00

摘要： Provided herein are recombinant CTLA-4 binding proteins, which are, inter alia, useful for the treatment of cancer. The recombinant proteins provided herein are, inter alia, capable of binding CTLA-4 proteins on a tumor cell. In a first aspect, there is provided a recombinant CTLA-4 binding protein including (i) a CTLA-4 binding domain; (ii) a CTLA-4 binding domain masking peptide; and (iii) a cleavable peptide linker connecting the CTLA-4 binding domain masking peptide to the CTLA-4 binding domain. In another aspect, there is provided a dimerizing domain covalently attached to the CTLA-4 binding domain, wherein the binding protein domains are bound together.

公开(公告)号：US11926652B2

公开(公告)日：2024-03-12

申请号：US15931077

申请日：2020-05-13

申请人： City of Hope ,  Thomas Jefferson University and Health System, Innovation Pillar

发明人： John Williams ,  Ulrich Rodeck ,  Miso Park ,  Kurt Jenkins

IPC分类号： C07K14/47 ,  A61K38/00 ,  A61K47/64 ,  A61K47/65 ,  C07K14/705

CPC分类号： C07K14/4703 ,  A61K47/64 ,  A61K47/65 ,  C07K14/70521 ,  A61K38/00 ,  C07K2319/055 ,  C07K2319/30 ,  C07K2319/50 ,  C07K2319/70 ,  C07K2319/74

摘要： Provided herein are recombinant CTLA-4 binding proteins, which are, inter alia, useful for the treatment of cancer. The recombinant proteins provided herein are, inter alia, capable of binding CTLA-4 proteins on a tumor cell. In a first aspect, there is provided a recombinant CTLA-4 binding protein including (i) a CTLA-4 binding domain; (ii) a CTLA-4 binding domain masking peptide; and (iii) a cleavable peptide linker connecting the CTLA-4 binding domain masking peptide to the CTLA-4 binding domain. In another aspect, there is provided a dimerizing domain covalently attached to the CTLA-4 binding domain, wherein the binding protein domains are bound together.

公开(公告)号：US11279752B2

公开(公告)日：2022-03-22

申请号：US16559561

申请日：2019-09-03

申请人： City of Hope ,  Thomas Jefferson University

发明人： John C. Williams ,  Ulrich Rodeck ,  Kurt Jenkins

IPC分类号： C07K14/82 ,  C07K16/28 ,  C07K14/47 ,  C07K14/705 ,  C07K14/71 ,  C12N9/64

摘要： Provided herein are recombinant masking proteins and recombinant ligand proteins useful in treating cancer, neurodegenerative disease, and cardiovascular disease. The recombinant masking proteins provided herein may, inter alia, be used as non-covalent masks of antagonists of, for example, cellular growth factors (e.g., TNF) or cell surface proteins (e.g., CTLA-4).