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公开(公告)号：US11866476B2
公开(公告)日：2024-01-09
申请号：US18089754
申请日：2022-12-28
发明人： Margaret Karow , Deborah Moore Lai , Dheeraj Tomar , Parker Johnson , Raphael Rozenfeld , Ronan O'Hagan , Huawei Qiu
CPC分类号： C07K14/55 , A61P35/00 , C07K14/5443 , A61K38/00 , C07K2317/52 , C07K2317/94 , C07K2319/30
摘要： Provided herein are cytokines or functional fragments thereof that, in some embodiments, are engineered to be masked by a masking moiety at one or more receptor binding site(s) of the cytokine or functional fragment thereof. In some embodiments, the cytokines are engineered to be activatable by a protease at a target site, such as in a tumor microenvironment, by including a proteolytically cleavable linker. In some embodiments, the proteolytically cleavable linker links the cytokine to the masking moiety, links the cytokine to a half-life extension domain, and/or links the masking moiety to a half-life extension domain. The masking moiety blocks, occludes, inhibits (e.g., decreases) or otherwise prevents (e.g., masks) the activity or binding of the cytokine to its cognate receptor or protein. Upon proteolytic cleavage of the cleavable linker at the target site, the cytokine becomes activated, which renders it capable of binding to its cognate receptor or protein with increased affinity.
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公开(公告)号：US11827686B2
公开(公告)日：2023-11-28
申请号：US17339810
申请日：2021-06-04
发明人： Margaret Karow , Deborah Moore Lai , Dheeraj Singh Tomar , Parker Johnson , Raphael Rozenfeld , Ronan O'Hagan , Huawei Qiu
CPC分类号： C07K14/55 , A61P35/00 , C07K14/5443 , A61K38/00 , C07K2317/52 , C07K2317/94 , C07K2319/30
摘要： Provided herein are cytokines or functional fragments thereof that, in some embodiments, are engineered to be masked by a masking moiety at one or more receptor binding site(s) of the cytokine or functional fragment thereof. In some embodiments, the cytokines are engineered to be activatable by a protease at a target site, such as in a tumor microenvironment, by including a proteolytically cleavable linker. In some embodiments, the proteolytically cleavable linker links the cytokine to the masking moiety, links the cytokine to a half-life extension domain, and/or links the masking moiety to a half-life extension domain. The masking moiety blocks, occludes, inhibits (e.g., decreases) or otherwise prevents (e.g., masks) the activity or binding of the cytokine to its cognate receptor or protein. Upon proteolytic cleavage of the cleavable linker at the target site, the cytokine becomes activated, which renders it capable of binding to its cognate receptor or protein with increased affinity.
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公开(公告)号：US20240141007A1
公开(公告)日：2024-05-02
申请号：US18352762
申请日：2023-07-14
CPC分类号： C07K14/55 , A61P35/00 , C07K16/246 , A61K38/00 , C07K2317/569 , C07K2317/622 , C07K2317/71 , C07K2319/30 , C07K2319/50
摘要： The present disclosure relates to cleavable carriers and cleavable carrier-linked cytokine prodrugs wherein the cleavable carrier is an engineered Fc domain comprising at least one tumor-associated protease cleavage site. Upon cleavage at the cleavage site of the carrier Fc domain, the cytokine is released from a masking moiety. The platform provides enzymatically induced prodrug activation. The present disclosure further provides pharmaceutical compositions comprising said cleavable carrier-linked cytokine prodrugs, their use as a medication as well as methods of treatment of diseases and administration.
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公开(公告)号：US20230144608A1
公开(公告)日：2023-05-11
申请号：US17932057
申请日：2022-09-14
IPC分类号： C07K14/715
CPC分类号： C07K14/7155 , A61K38/00
摘要： The present invention discloses proteolytically cleavable peptide (CP) substrates, polypeptides, polypeptide constructs and prodrug constructs comprising the proteolytically cleavable peptides (e.g., cytokine prodrugs), and methods of use of the same.
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公开(公告)号：US20230235006A1
公开(公告)日：2023-07-27
申请号：US18089754
申请日：2022-12-28
发明人： Margaret KAROW , Deborah Moore LAI , Dheeraj TOMAR , Parker JOHNSON , Raphael ROZENFELD , Ronan O'HAGAN , Huawei QIU
CPC分类号： C07K14/55 , A61P35/00 , C07K14/5443 , A61K38/00
摘要： Provided herein are cytokines or functional fragments thereof that, in some embodiments, are engineered to be masked by a masking moiety at one or more receptor binding site(s) of the cytokine or functional fragment thereof. In some embodiments, the cytokines are engineered to be activatable by a protease at a target site, such as in a tumor microenvironment, by including a proteolytically cleavable linker. In some embodiments, the proteolytically cleavable linker links the cytokine to the masking moiety, links the cytokine to a half-life extension domain, and/or links the masking moiety to a half-life extension domain. The masking moiety blocks, occludes, inhibits (e.g., decreases) or otherwise prevents (e.g., masks) the activity or binding of the cytokine to its cognate receptor or protein. Upon proteolytic cleavage of the cleavable linker at the target site, the cytokine becomes activated, which renders it capable of binding to its cognate receptor or protein with increased affinity.
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公开(公告)号：US20230159603A1
公开(公告)日：2023-05-25
申请号：US17995162
申请日：2021-03-31
发明人： Raphael ROZENFELD , Ugur ESKIOCAK , Huawei QIU , Parker JOHNSON , Kurt Allen JENKINS , Magali PEDERZOLI-RIBEIL , Dheeraj Singh TOMAR , Rebekah Kay O'DONNELL
IPC分类号： C07K14/54 , C07K14/715 , A61P35/00
CPC分类号： C07K14/5434 , C07K14/7155 , A61P35/00 , C07K2319/50 , C07K2319/30 , A61K38/00
摘要： The present invention relates to masked IL-12 cytokines, comprising an IL-12 cytokine or functional fragment thereof, a masking moiety and a proteolytically cleavable linker. The masking moiety masks the IL-12 cytokine or functional fragment thereof thereby reducing or preventing binding of the IL-cytokine or functional fragment thereof to its cognate receptor, but upon proteolytic cleavage of the cleavable linker at a target site, the IL-12 cytokine or functional fragment thereof becomes activated, which renders it capable or more capable of binding to its cognate receptor.
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公开(公告)号：US20230028959A1
公开(公告)日：2023-01-26
申请号：US17339810
申请日：2021-06-04
发明人： Margaret KAROW , Deborah Moore LAI , Dheeraj Singh TOMAR , Parker JOHNSON , Raphael ROZENFELD , Ronan O'HAGAN , Huawei QIU
摘要： Provided herein are cytokines or functional fragments thereof that, in some embodiments, are engineered to be masked by a masking moiety at one or more receptor binding site(s) of the cytokine or functional fragment thereof. In some embodiments, the cytokines are engineered to be activatable by a protease at a target site, such as in a tumor microenvironment, by including a proteolytically cleavable linker. In some embodiments, the proteolytically cleavable linker links the cytokine to the masking moiety, links the cytokine to a half-life extension domain, and/or links the masking moiety to a half-life extension domain. The masking moiety blocks, occludes, inhibits (e.g., decreases) or otherwise prevents (e.g., masks) the activity or binding of the cytokine to its cognate receptor or protein. Upon proteolytic cleavage of the cleavable linker at the target site, the cytokine becomes activated, which renders it capable of binding to its cognate receptor or protein with increased affinity.
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公开(公告)号：US20220064301A1
公开(公告)日：2022-03-03
申请号：US17417244
申请日：2019-12-26
发明人： Margaret Karow
摘要： The invention provides anti-CTLA4 binding proteins (e.g., antibodies, bispecific antibodies, and chimeric receptors) and their use in treating and preventing cancer, as well as compositions and kits comprising the anti-CTLA4 binding proteins.
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公开(公告)号：US20210002343A1
公开(公告)日：2021-01-07
申请号：US17002742
申请日：2020-08-25
发明人： Margaret KAROW , Deborah Moore LAI , Dheeraj Singh TOMAR , Parker JOHNSON , Raphael ROZENFELD , Ronan O'HAGAN , Huawei QIU
摘要： Provided herein are cytokines or functional fragments thereof that, in some embodiments, are engineered to be masked by a masking moiety at one or more receptor binding site(s) of the cytokine or functional fragment thereof. In some embodiments, the cytokines are engineered to be activatable by a protease at a target site, such as in a tumor microenvironment, by including a proteolytically cleavable linker. In some embodiments, the proteolytically cleavable linker links the cytokine to the masking moiety, links the cytokine to a half-life extension domain, and/or links the masking moiety to a half-life extension domain. The masking moiety blocks, occludes, inhibits (e.g., decreases) or otherwise prevents (e g masks) the activity or binding of the cytokine to its cognate receptor or protein. Upon proteolytic cleavage of the cleavable linker at the target site, the cytokine becomes activated, which renders it capable of binding to its cognate receptor or protein with increased affinity.
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公开(公告)号：US11827685B2
公开(公告)日：2023-11-28
申请号：US17339801
申请日：2021-06-04
发明人： Margaret Karow , Deborah Moore Lai , Dheeraj Singh Tomar , Parker Johnson , Raphael Rozenfeld , Ronan O'Hagan , Huawei Qiu
CPC分类号： C07K14/55 , A61P35/00 , C07K14/5443 , A61K38/00 , C07K2317/52 , C07K2317/94 , C07K2319/30
摘要： Provided herein are cytokines or functional fragments thereof that, in some embodiments, are engineered to be masked by a masking moiety at one or more receptor binding site(s) of the cytokine or functional fragment thereof. In some embodiments, the cytokines are engineered to be activatable by a protease at a target site, such as in a tumor microenvironment, by including a proteolytically cleavable linker. In some embodiments, the proteolytically cleavable linker links the cytokine to the masking moiety, links the cytokine to a half-life extension domain, and/or links the masking moiety to a half-life extension domain. The masking moiety blocks, occludes, inhibits (e.g., decreases) or otherwise prevents (e.g., masks) the activity or binding of the cytokine to its cognate receptor or protein. Upon proteolytic cleavage of the cleavable linker at the target site, the cytokine becomes activated, which renders it capable of binding to its cognate receptor or protein with increased affinity.
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