Periostin antibodies and methods of using the same
Inventors
Abbott, Karen • Scholler, Nathalie
Assignees
Bio Ventures LLC • SRI International Inc • BioVentures LLC
Publication Number
US-12281171-B2
Publication Date
2025-04-22
Expiration Date
2039-03-19
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Abstract
The present inventors have developed antigen-binding reagents and antigen-binding conjugates that recognize a cancer-specific glycan (carbohydrate) modification on the human Periostin protein. Various in vitro and in vivo diagnostic and/or therapeutic methods using these compositions are also disclosed herein specifically for treating cancers that have amplification of the Mgat3 gene.
Core Innovation
The invention provides antigen-binding reagents and antigen-binding conjugates that recognize a cancer-specific glycan modification on the human Periostin protein. These reagents, including scFv antibodies such as the C9 biobody, are specifically designed to bind to a bisecting N-glycan epitope present on human Periostin glycoproteins, which is distinctively expressed on cancer cells, particularly those with amplification of the Mgat3 gene.
The problem addressed by this invention stems from the challenge of target specificity in cancer diagnostics and therapy. Traditional peptide antigens often do not discriminate adequately between normal and cancer cells due to similar expression patterns. While tumor-specific glycosylation changes in proteins suggest promise for more specific targeting, few antibodies exist that can selectively recognize the unique carbohydrate moieties (tumor-associated glycans) found on cancer cells.
The core innovation resolves this challenge by providing antibodies, particularly the C9 scFv, that selectively bind to a unique bisecting N-glycan on the Periostin protein—found predominately in various cancers, including ovarian cancer, due to altered glycosyltransferase expression and Mgat3 gene amplification. These antigen-binding reagents can be formulated as diagnostic and therapeutic tools, including conjugates with imaging or therapeutic agents, enabling targeted imaging, detection, and treatment of cancers characterized by this glycan modification.
Claims Coverage
The patent claims cover five main inventive features, focusing on antigen-binding reagents and their use in cancer detection, imaging, and therapy.
Antigen-binding reagent with specific variable regions recognizing bisecting N-glycan epitope of human Periostin
An antigen-binding reagent comprising a heavy chain variable region comprising SEQ ID NO: 5 and a light chain variable region comprising SEQ ID NO: 6, which specifically binds to a bisecting N-glycan epitope of the human Periostin glycoprotein.
Antigen-binding conjugate linked to functional agents
An antigen-binding conjugate composed of the antigen-binding reagent described above linked to an agent, where the agent is selected from a detectable imaging agent, a therapeutic agent, or an immunopolypeptide.
Cell comprising antigen-binding reagent
A cell comprising the specific antigen-binding reagent that recognizes the bisecting N-glycan epitope of the human Periostin glycoprotein.
Pharmaceutical composition with antigen-binding conjugate
A pharmaceutical composition comprising the antigen-binding conjugate (where the agent can be a detectable imaging agent, therapeutic agent, or immunopolypeptide) and a pharmaceutical carrier.
Method for imaging cancer cells using antigen-binding conjugate
A method for imaging cancer cells in a subject comprising administration of an effective amount of the antigen-binding conjugate linked to a detectable imaging agent, and generating an image of at least a portion of the subject using an imaging modality, with imaging of the cells bound to the conjugate being indicative of cancer cells.
Method of detecting cancer cells in a subject sample using antigen-binding conjugate
A method of detecting cancer cells in a subject sample by obtaining the sample, contacting it with the antigen-binding conjugate, and detecting binding of the conjugate to cells, with binding indicative of cancer cells.
In conclusion, the claims comprehensively protect antigen-binding reagents specific for cancer-associated bisecting N-glycan Periostin epitopes, their functional conjugates, compositions, use in cellular and pharmaceutical contexts, and methods for detecting and imaging cancer using these reagents.
Stated Advantages
Provides tumor specificity by targeting a cancer-specific glycan epitope on Periostin, distinguishing cancer cells from normal cells.
Enables the development of both diagnostic and therapeutic applications through selective recognition of tumor-associated bisecting N-glycans.
Facilitates imaging and detection of cancers that amplify the Mgat3 gene, allowing for targeted intervention.
Allows creation of antigen-binding conjugates with imaging or therapeutic agents for targeted cancer cell imaging or treatment.
Documented Applications
Imaging of cancer cells in subjects using antigen-binding conjugates linked to detectable imaging agents via modalities such as ultrasound, PET, SPECT, NMRI, optical imaging, and CT.
Detection of cancer cells in a subject sample by contacting the sample with the antigen-binding conjugate and detecting binding to cancer cells.
Treatment of cancers, particularly those with Mgat3 gene amplification, using antigen-binding reagents, conjugates, or compositions that target the bisecting N-glycan epitope on Periostin.
Interested in licensing this patent?