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公开(公告)号：US20230192798A1
公开(公告)日：2023-06-22
申请号：US17938536
申请日：2022-10-06
发明人： Alexey Yevgenyevich Berezhnoy , Nicole G. Lapuyade , Na Cai , Michael B. Winter , Kenneth Wong , Madan M. Paidhungat , Dylan L. Daniel , Erwan Le Scolan
CPC分类号： C07K14/56 , C07K16/2896 , A61P35/00
摘要： Provided herein are methods of treating a subject by administering a combination of an activatable cytokine construct (ACC) and a PD-1/PD-L1 pathway inhibitor in which the ACC includes: a first monomer construct including an optional first peptide mask (PM1), an optional third cleavable moiety (CM3), a first mature cytokine protein (CP1), a first cleavable moiety (CM1), and a first dimerization domain (DD1), wherein the CM1 is positioned between the CP1 and the DD1; and a second monomer construct including an optional second peptide mask (PM2), an optional forth cleavable moiety (CM4), a second mature cytokine protein (CP2), a second cleavable moiety (CM2), and a second dimerization domain (DD2), wherein the CM2 is positioned between the CP2 and the DD2; wherein the DD1 and the DD2 bind to each other thereby forming a dimer of the first monomer construct and the second monomer construct; and where the ACC is characterized by a reduction in at least one activity of the CP1 and/or CP2 as compared to a control level of the at least one activity of the CP1 and/or CP2.
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公开(公告)号：US12091442B2
公开(公告)日：2024-09-17
申请号：US17824294
申请日：2022-05-25
发明人： Sayantan Mitra , Nicole G. Lapuyade , Hikmat Haizar Assi , Madan M. Paidhungat , Dylan L. Daniel , Erwan Le Scolan , Walter A. Bogdanoff , Na Cai , Hsin Wang
IPC分类号： C07K14/56
CPC分类号： C07K14/56 , C07K2319/02 , C07K2319/30
摘要： Provided herein are activatable cytokine constructs that include: (a) a first monomer construct comprising a first mature cytokine protein (CP1), a first cleavable moiety (CM1), and a first dimerization domain (DD1), wherein the CM1 is positioned between the CP1 and the DD1; and (b) a second monomer construct comprising a second mature cytokine protein (CP2), a second cleavable moiety (CM2), and a second dimerization domain (DD2), where the CM2 is positioned between the CP2 and the DD2, where: the CM1 and the CM2 function as a substrate for a protease; the DD1 and the DD2 bind each other; and where the ACC is characterized by a reduction in at least one activity of the CP1 and/or CP2 as compared to a control level of the at least one activity of the CP1 and/or CP2.
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公开(公告)号：US11365233B2
公开(公告)日：2022-06-21
申请号：US17227017
申请日：2021-04-09
发明人： Sayantan Mitra , Nicole G. Lapuyade , Hikmat Haizar Assi , Madan M. Paidhungat , Dylan L. Daniel , Erwan Le Scolan , Walter A. Bogdanoff , Na Cai , Hsin Wang
IPC分类号： C07K14/56
摘要： Provided herein are activatable cytokine constructs that include: (a) a first monomer construct comprising a first mature cytokine protein (CP1), a first cleavable moiety (CM1), and a first dimerization domain (DD1), wherein the CM1 is positioned between the CP1 and the DD1; and (b) a second monomer construct comprising a second mature cytokine protein (CP2), a second cleavable moiety (CM2), and a second dimerization domain (DD2), where the CM2 is positioned between the CP2 and the DD2, where: the CM1 and the CM2 function as a substrate for a protease; the DD1 and the DD2 bind each other; and where the ACC is characterized by a reduction in at least one activity of the CP1 and/or CP2 as compared to a control level of the at least one activity of the CP1 and/or CP2.
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公开(公告)号：US11667687B2
公开(公告)日：2023-06-06
申请号：US17696222
申请日：2022-03-16
发明人： Sayantan Mitra , Nicole G. Lapuyade , Hikmat Haizar Assi , Madan M. Paidhungat , Dylan L. Daniel , Erwan Le Scolan , Walter A. Bogdanoff , Na Cai , Hsin Wang , Alexey Yevgenyevich Berezhnoy
IPC分类号： C07K14/56 , C07K14/565 , C07K14/57
CPC分类号： C07K14/56 , C07K14/565 , C07K14/57 , C07K2319/30 , C07K2319/50 , C07K2319/70
摘要： Provided herein are activatable cytokine constructs that include: (a) a first monomer construct comprising a first peptide mask (PM1), a third cleavable moiety (CM3), a first mature cytokine protein (CP1), a first cleavable moiety (CM1), and a first dimerization domain (DD1), wherein the CM1 is positioned between the CP1 and the DD1, and the CM3 is positioned between the PM1 and CP1; and (b) a second monomer construct comprising a second mature cytokine protein (CP2), a second cleavable moiety (CM2), and a second dimerization domain (DD2), where the CM2 is positioned between the CP2 and the DD2, where: the DD1 and the DD2 bind each other; and where the ACC is characterized by a reduction in at least one activity of the CP1 and/or CP2 as compared to a control level of the at least one activity of the CP1 and/or CP2.
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公开(公告)号：US20220402990A1
公开(公告)日：2022-12-22
申请号：US17824294
申请日：2022-05-25
发明人： Sayantan Mitra , Nicole G. Lapuyade , Hikmat Haizar Assi , Madan M. Paidhungat , Dylan L. Daniel , Erwan Le Scolan , Walter A. Bogdanoff , Na Cai , Hsin WANG
IPC分类号： C07K14/56
摘要： Provided herein are activatable cytokine constructs that include: (a) a first monomer construct comprising a first mature cytokine protein (CP1), a first cleavable moiety (CM1), and a first dimerization domain (DD1), wherein the CM1 is positioned between the CP1 and the DD1; and (b) a second monomer construct comprising a second mature cytokine protein (CP2), a second cleavable moiety (CM2), and a second dimerization domain (DD2), where the CM2 is positioned between the CP2 and the DD2, where: the CM1 and the CM2 function as a substrate for a protease; the DD1 and the DD2 bind each other; and where the ACC is characterized by a reduction in at least one activity of the CP1 and/or CP2 as compared to a control level of the at least one activity of the CP1 and/or CP2.
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公开(公告)号：US20210317177A1
公开(公告)日：2021-10-14
申请号：US17227017
申请日：2021-04-09
发明人： Sayantan Mitra , Nicole G. Lapuyade , Hikmat Haizar Assi , Madan M. Paidhungat , Dylan D. Daniel , Erwan Le Scolan , Walter A. Bogdanoff , Na Cai , Hsin Wang
IPC分类号： C07K14/56
摘要： Provided herein are activatable cytokine constructs that include: (a) a first monomer construct comprising a first mature cytokine protein (CP1), a first cleavable moiety (CM1), and a first dimerization domain (DD1), wherein the CM1 is positioned between the CP1 and the DD1; and (b) a second monomer construct comprising a second mature cytokine protein (CP2), a second cleavable moiety (CM2), and a second dimerization domain (DD2), where the CM2 is positioned between the CP2 and the DD2, where: the CM1 and the CM2 function as a substrate for a protease; the DD1 and the DD2 bind each other; and where the ACC is characterized by a reduction in at least one activity of the CP1 and/or CP2 as compared to a control level of the at least one activity of the CP1 and/or CP2.
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