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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：US11053294B2
公开(公告)日：2021-07-06
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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公开(公告)号：US11718655B2
公开(公告)日：2023-08-08
申请号：US17716873
申请日：2022-04-08
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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