Compositions comprising annexin V and HPV tumor antigen fusion polypeptides and methods for making and use
Inventors
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Assignees
MemberJohns Hopkins UniversityJohns Hopkins UniversityFounded in 1876, Johns Hopkins University is recognized as the first research university in the United States. It advances interdisciplinary education, high-impact research, and global outreach, supporting knowledge translation, technological innovation, and community partnerships. The university fosters academic excellence, innovation incubation, outreach, and inclusion across multiple campuses in Baltimore, integrating into the city's social, economic, and cultural life.
Founded in 1876, Johns Hopkins University is recognized as the first research university in the United States. It advances interdisciplinary education, high-impact research, and global outreach, supporting knowledge translation, technological innovation, and community partnerships. The university fosters academic excellence, innovation incubation, outreach, and inclusion across multiple campuses in Baltimore, integrating into the city's social, economic, and cultural life.
Publication Number
US-12649767-B2
Publication Date
2026-06-09
Expiration Date
Abstract
The present invention provides synthetic polypeptides comprising an annexin V protein, or a functional portion or fragment or variant thereof, conjugated to a tumor antigen, or a functional portion or fragment or variant thereof. The invention further provides methods for making said synthetic polypeptides and their use in the treatment of proliferative diseases such as cancer and tumors originating therefrom.
Core Innovation
The invention relates to immune checkpoint agents based on annexin V–tumor antigen fusion polypeptides. The fusion polypeptides comprise an annexin V protein conjugated to an antigen, thereby targeting phosphatidylserine (PS)-rich, thrombin-activated and tumor-activated platelets in the tumor microenvironment. Examples include AnnE7 and an annexin V–HPV tumor antigen fusion polypeptide, such as AnnV–AH5 or other antigens.
The document addresses the need to modulate the tumor microenvironment and improve anti-tumor immunity through immune checkpoint-type activity. Administration following chemotherapy enhances antigen-specific CD8+ T-cell responses and reduces immunosuppressive tumor microenvironment features, including Tregs, MDSCs, and PD-L1. The document further describes a shift in macrophage M1/M2 profile.
The document provides mechanistic evidence that anti-tumor efficacy depends on platelet presence and platelet-derived CD40L. It also describes synergy with additional checkpoint inhibitors, including anti-PD-1/PD-L1 and anti-TIM-3, and agents such as anti-TGF-β. The fusion polypeptides are further described with embodiment scope including annexin V–antigen fusion orientation, optional detectable moieties, and nucleic acids encoding the fusion proteins.
Claims Coverage
The independent claims cover synthetic annexin V–antigen conjugated polypeptides consisting essentially of an annexin V protein or functional portion or fragment thereof conjugated to an antigen or functional portion or fragment thereof. The claim set includes 6 inventive features covering composition, therapeutic use, post-chemotherapy use, fusion architecture, and specific antigen selections.
Annexin V–antigen conjugated synthetic polypeptide
A synthetic polypeptide consisting essentially of an annexin V protein, or a functional portion or fragment thereof, conjugated to an antigen, or a functional portion or fragment thereof.
Therapeutic treatment of hyperproliferative disease with the annexin V–antigen polypeptide
A method for treating a subject suffering from or susceptible to a hyperproliferative disease by administering an effective amount of the synthetic annexin V–antigen polypeptide.
Post-chemotherapy administration of the annexin V–antigen polypeptide
A method for treating a subject suffering from or susceptible to a hyperproliferative disease by administering one or more doses of a chemotherapeutic agent and thereafter administering an effective amount of the synthetic annexin V–antigen polypeptide.
Annexin V–antigen fusion architecture with N-terminal annexin V and C-terminal antigen
The polypeptide comprises a N-terminal end and a C-terminal end, wherein the N-terminal portion of the fusion protein comprises an annexin V protein, or a functional portion or fragment or variant thereof, conjugated to an antigen, or a functional portion or fragment or variant thereof, at the C-terminal portion of the fusion protein.
Tumor-associated antigen AH5 in annexin V–antigen polypeptide
The tumor associated antigen is AH5 (SPSYAYHQF) (SEQ ID NO: 13).
HPV tumor antigen selection for the annexin V–antigen polypeptide
The HPV tumor antigen is derived from HPV having a subtype selected from the group consisting of 16, 18, 31, 33, 35, 39, 45, 51, 52, and 58.
The inventive coverage centers on synthetic polypeptides that consist essentially of an annexin V protein conjugated to an antigen, with claim-dependent refinements for therapeutic use, post-chemotherapy administration, fusion placement architecture, and antigen selections including AH5 and HPV tumor antigens constrained to enumerated HPV subtypes.
Stated Advantages
Administration following chemotherapy enhances antigen-specific CD8+ T-cell responses.
Reduces immunosuppressive tumor microenvironment features, including Tregs, MDSCs, and PD-L1.
Shifts macrophage M1/M2 profile.
Prolongs survival in tumor-bearing mouse models.
Anti-tumor efficacy is dependent on platelet presence and platelet-derived CD40L.
Provides synergy with additional checkpoint inhibitors such as anti-PD-1/PD-L1 and anti-TIM-3.
Documented Applications
Treating a subject suffering from or susceptible to a hyperproliferative disease using an effective amount of the synthetic annexin V–antigen polypeptide.
Treating hyperproliferative disease using a regimen that administers one or more doses of a chemotherapeutic agent and thereafter administers an effective amount of the synthetic annexin V–antigen polypeptide.
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