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1. 发明公开

US20240335557A1 BIS-BENZIMIDAZOLE STING AGONIST IMMUNOCONJUGATES, AND USES THEREOF 审中-公开
公开(公告)号：US20240335557A1
公开(公告)日：2024-10-10
申请号：US18573094
申请日：2022-06-24
申请人： BOLT BIOTHERAPEUTICS, INC.
发明人： Gary BRANDT , Romas KUDIRKA , Brian SAFINA , Matthew ZHOU
IPC分类号： A61K47/68 , A61K47/60
CPC分类号： A61K47/6853 , A61K47/60 , A61K47/6803 , A61K47/6851 , A61K47/6889
摘要： STING pathway agonism has emerged as a potential therapeutic mechanism to stimulate an innate anti-tumor immune response. While in principle systemic administration of a STING agonist would have many therapeutic benefits, including the delivery of STING to all tumor lesions, such an approach may be limited by toxicity. Antibody-drug conjugates (ADCs) constitute a proven therapeutic modality that is ideally suited to enable systemic administration without associated toxicity concerns via a targeted delivery strategy. Herein, we demonstrate that systemically administered STING agonist ADCs have greater anti-tumor activity as well as greatly improved tolerability compared to an intravenously (IV) administered, unconjugated (free) agonist. We generated novel STING agonist ADCs by leveraging our Immunosynthen platform, in which the chemical scaffold for bioconjugation is optimized for the STING agonist, resulting in an ADC that has desirable physicochemical and drug-like properties. We have studied the in vitro activity and mechanism of action of STING agonist ADCs in monoculture and co-culture systems. STING agonist ADCs were at least 100-fold more potent in inducing interferon and cytokines as well as tumor cell-killing relative to free agonist. STING agonist ADCs against several targets (antigens) have been evaluated for anti-tumor activity and pharmacodynamic and pharmacokinetic properties in multiple xenograft and syngeneic models. A single administration of STING agonist ADC resulted in target-dependent, durable, and complete regressions. Importantly, the STING agonist ADC led to an increase in tumor-localized inflammatory cytokines and significant immune cell infiltration, while levels of systemic cytokines remained low. In contrast, IV administered free agonist induced up to 100-fold higher levels of systemic cytokines with concomitant body weight loss but only modest tumor growth delay. In summary, Immunosynthen represents a novel STING agonist ADC platform. We have demonstrated target-dependent anti-tumor immune responses in vitro and in vivo for multiple targets, tumor models, and mouse strains. In each case the STING agonist ADC was more active and better tolerated than the IV administered free agonist.

2. 发明公开

US20240042050A1 ANTI-HER2 IMMUNOCONJUGATES, AND USES THEREOF 审中-公开
公开(公告)号：US20240042050A1
公开(公告)日：2024-02-08
申请号：US18038897
申请日：2021-12-10
申请人： BOLT BIOTHERAPEUTICS, INC.
发明人： Shelley Erin ACKERMAN , Michael N. ALONSO , Romas KUDIRKA , Arthur LEE , Brian SAFINA , Matthew ZHOU
IPC分类号： A61K47/68
CPC分类号： A61K47/6855 , A61K47/6803
摘要： The invention provides immunoconjugates of Formula I comprising an anti-HER2 antibody linked by conjugation to one or more 8-phenyl-2-aminobenzazepine derivatives. The invention also provides 8-phenyl-2-aminobenzazepine derivative intermediate compositions comprising a reactive functional group. Such intermediate compositions are suitable substrates for formation of the immunoconjugates through a linker or linking moiety. The invention further provides methods of treating cancer with the immunoconjugates.

3. 发明申请

US20230111340A1 ANTIBODY ADJUVANT CONJUGATES 有权
公开(公告)号：US20230111340A1
公开(公告)日：2023-04-13
申请号：US17818176
申请日：2022-08-08
申请人： The Board of Trustees of the Leland Stanford Junior University , Bolt Biotherapeutics, Inc.
发明人： Michael Nathaniel Alonso , Edgar George Engleman , Shelley Erin Ackerman , Justin Kenkel , Arthur Lee , David Y. Jackson
IPC分类号： A61K47/68 , A61P35/00 , C07K16/28
摘要： The invention provides an immunoconjugate comprising an antibody construct which includes an antigen binding domain and an Fc domain, an adjuvant moiety, and a linker, wherein each adjuvant moiety is covalently bonded to the antibody via the linker. Methods for treating cancer with the immunoconjugates of the invention are also described.

4. 发明申请

US20220153849A1 Anti-Dectin-2 Antibodies 有权
公开(公告)号：US20220153849A1
公开(公告)日：2022-05-19
申请号：US17592323
申请日：2022-02-03
申请人： Bolt Biotherapeutics, Inc.
发明人： Shelley Erin Ackerman , David Dornan , Karla A. Henning , Justin A. Kenkel
IPC分类号： C07K16/28
摘要： The invention relates to dendritic cell-associated C-type lectin 2 (Dectin-2) binding agents, nucleic acids comprising the inventive binding agents, vectors and cells comprising the inventive nucleic acids, and compositions thereof. The invention also relates to methods of providing the inventive binding agents, methods for treating a disease, disorder, or condition in a mammal, and methods of stimulating an antigen presenting cell.

5. 发明申请

US20220001022A1 Immunoconjugates Targeting HER2 有权
公开(公告)号：US20220001022A1
公开(公告)日：2022-01-06
申请号：US17465284
申请日：2021-09-02
申请人： Bolt Biotherapeutics, Inc. , The Board of Trustees of The Leland Stanford Junior University
发明人： Shelley Erin Ackerman , Michael N. Alonso , David Y. Jackson , Arthur Lee , Edgar George Engleman
IPC分类号： A61K47/68 , A61K39/395
摘要： The invention provides an immunoconjugate of formula: or pharmaceutically acceptable salt thereof, wherein subscript r is an integer from 1 to 10, subscript n is an integer from about 2 to about 25, and “Ab” is an antibody construct that has an antigen binding domain that binds HER2. The invention further provides compositions comprising and methods of treating cancer with the immunoconjugate.

6. 发明授权

US11110178B2 Antibody adjuvant conjugates 有权
公开(公告)号：US11110178B2
公开(公告)日：2021-09-07
申请号：US16817864
申请日：2020-03-13
申请人： The Board of Trustees of the Leland Stanford Junior University , Bolt Biotherapeutics, Inc.
发明人： Michael Nathaniel Alonso , Edgar George Engleman , Shelley Erin Ackerman , Justin Kenkel , Arthur Lee , David Y. Jackson
IPC分类号： A61K47/68 , C07K16/28 , C07K16/30 , A61P35/00
摘要： The invention provides an immunoconjugate comprising an antibody construct which includes an antigen binding domain and an Fc domain, an adjuvant moiety, and a linker, wherein each adjuvant moiety is covalently bonded to the antibody via the linker. Methods for treating cancer with the immunoconjugates of the invention are also described.

7. 发明申请

US20210128744A1 THIENOAZEPINE IMMUNOCONJUGATES, AND USES THEREOF 有权
公开(公告)号：US20210128744A1
公开(公告)日：2021-05-06
申请号：US17078467
申请日：2020-10-23
申请人： BOLT BIOTHERAPEUTICS, INC.
发明人： Romas Kudirka , Brian Safina
IPC分类号： A61K47/68 , C07K16/28
摘要： The invention provides immunoconjugates of Formula I comprising an antibody linked by conjugation to one or more thienoazepine derivatives. The invention also provides thienoazepine derivative intermediate compositions comprising a reactive functional group. Such intermediate compositions are suitable substrates for formation of the immunoconjugates through a linker or linking moiety. The invention further provides methods of treating cancer with the immunoconjugates.

8. 发明申请

US20190076547A1 ANTIBODY ADJUVANT CONJUGATES 审中-公开
公开(公告)号：US20190076547A1
公开(公告)日：2019-03-14
申请号：US16140309
申请日：2018-09-24
申请人： The Board of Trustees of the Leland Stanford Junior University , Bolt Biotherapeutics, Inc.
发明人： Michael Nathaniel Alonso , Edgar George Engleman , Shelley Erin Ackerman , Justin Kenkel , Arthur Lee , David Y. Jackson
IPC分类号： A61K47/68 , C07K16/28 , A61P35/00
摘要： The invention provides an immunoconjugate comprising an antibody construct which includes an antigen binding domain and an Fc domain, an adjuvant moiety, and a linker, wherein each adjuvant moiety is covalently bonded to the antibody via, the linker. Methods for treating cancer with the immunoconjugates of the invention are also described.

9. 发明申请

US20190015516A1 ANTIBODY ADJUVANT CONJUGATES 审中-公开
公开(公告)号：US20190015516A1
公开(公告)日：2019-01-17
申请号：US16129118
申请日：2018-09-12
申请人： Bolt Biotherapeutics, Inc.
发明人： David Y. Jackson , Michael Nathaniel Alonso , Arthur Lee
IPC分类号： A61K47/55 , A61P35/00 , A61K47/68
摘要： The invention provides an immunoconjugate comprising an antibody construct which includes an antigen binding domain and an Fc domain, an adjuvant moiety, and a linker, wherein each adjuvant moiety is covalently bonded to the antibody via the linker which comprises an ethylene glycol group or glycine residue. Methods for treating cancer with the immunoconjugates of the invention are also described.

10. 发明公开

US20240197899A1 2-AMINO-4-CARBOXAMIDE-BENZAZEPINE IMMUNOCONJUGATES, AND USES THEREOF 审中-公开
公开(公告)号：US20240197899A1
公开(公告)日：2024-06-20
申请号：US18283071
申请日：2022-03-25
申请人： BOLT BIOTHERAPEUTICS, INC.
发明人： Gary BRANDT , Romas KUDIRKA , Brian SAFINA
IPC分类号： A61K47/68 , A61K47/60
CPC分类号： A61K47/6803 , A61K47/60 , A61K47/6849 , A61K47/6851 , A61K47/6853 , A61K47/6889
摘要： The invention provides immunoconjugates of Formula I comprising an antibody linked by conjugation to one or more 2-amino-4-carboxamide-benzazepine derivatives. The invention also provides 2-amino-4-carboxamide-benzazepine derivative intermediate compositions comprising a reactive functional group. Such intermediate compositions are suitable substrates for formation of the immunoconjugates through a linker or linking moiety. The invention further provides methods of treating cancer with the immunoconjugates.

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