Antibodies for Siglec-15 and methods of use thereof
Inventors
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Assignees
Member
NextCure, Inc.NextCure, Inc. is a clinical-stage biopharmaceutical company dedicated to discovering and developing innovative immunomedicines to treat cancer. The company focuses on patients who do not respond to current therapies, whose cancer progresses despite treatment, and those with cancer types not adequately addressed by available therapies. NextCure leverages its proprietary FIND-IOTM technology to identify novel targets and develop therapies that modulate immune responses within the tumor microenvironment, aiming to restore anti-tumor activity and address significant unmet medical needs.
NextCure, Inc. is a clinical-stage biopharmaceutical company dedicated to discovering and developing innovative immunomedicines to treat cancer. The company focuses on patients who do not respond to current therapies, whose cancer progresses despite treatment, and those with cancer types not adequately addressed by available therapies. NextCure leverages its proprietary FIND-IOTM technology to identify novel targets and develop therapies that modulate immune responses within the tumor microenvironment, aiming to restore anti-tumor activity and address significant unmet medical needs.
Publication Number
US-11390675-B2
Publication Date
2022-07-19
Expiration Date
2037-09-21
Abstract
Siglec-15 binding molecules are provides. The molecules are typically an antibody or antigen binding fragment thereof that immunospecifically binds to Siglec-15. Siglec-15 ligand-binding molecules are also provided. The molecules are typically Siglec-15 polypeptide or fusion protein. Methods of using the molecules to reduce Siglec-15 mediated immunosuppression in a subject in need thereof are also provided.
Core Innovation
Siglec-15 binding molecules, particularly monoclonal antibodies or antigen-binding fragments thereof, are developed to specifically recognize and bind to Siglec-15. These antibodies are characterized at the molecular level by their complementarity determining regions (CDRs) and variable regions, conferring highly specific binding properties to the Siglec-15 epitope. The patent provides detailed sequence information for the light and heavy chain CDRs and variable regions of these antibodies, including both mouse-derived and humanized versions.
The invention addresses the need for tools and therapeutic strategies to modulate Siglec-15 and its downstream signaling. Siglec-15 has been implicated in immune suppression, particularly by enhancing TGF-β secretion from myeloid cells such as macrophages, thereby contributing to tumor progression and creating an immunosuppressive microenvironment. By blocking Siglec-15 interactions with its ligands or counter-receptors, these antibodies are capable of reducing Siglec-15-mediated immune suppression and can enhance immunological responses or reverse suppression in a subject in need thereof.
Additionally, the patent provides methods for using these Siglec-15 antibodies in pharmaceutical compositions for treating diseases and conditions associated with Siglec-15 function, including cancer, infections, inflammations, autoimmune diseases, as well as bone-related disorders by affecting osteoclast differentiation and bone resorption. The document further describes diagnostic and monitoring applications, leveraging the antibodies’ ability to detect Siglec-15 expression in tissues or peripheral samples.
Claims Coverage
There is one independent claim providing a key inventive feature centered on a specific Siglec-15 antibody characterized by its unique CDR sequences and variable regions.
Monoclonal antibody with defined Siglec-15 CDR sequences
A monoclonal antibody or antigen-binding fragment thereof that binds specifically to SIGLEC-15, wherein the antibody comprises these six CDR sequences: - Three heavy chain CDRs (HCDR1: SEQ ID NO:208, HCDR2: SEQ ID NO:374, HCDR3: SEQ ID NO:71) - Three light chain CDRs (LCDR1: SEQ ID NO:198, LCDR2: SEQ ID NO:202, LCDR3: SEQ ID NO:43). This structural definition confers unique specificity for SIGLEC-15. The antibody may include the heavy chain variable region with amino acid sequence SEQ ID NO:207 and the light chain variable region with sequence SEQ ID NO:201.
Pharmaceutical composition with the defined antibody
A pharmaceutical composition comprising the above-defined monoclonal antibody or antigen-binding fragment in combination with an excipient. This composition is intended for administration and therapeutic use, leveraging the antibody's specific SIGLEC-15 binding profile.
The inventive features are focused on a monoclonal antibody defined by precise heavy and light chain CDR sequences and variable regions conferring specificity to Siglec-15, as well as pharmaceutical compositions comprising this antibody.
Stated Advantages
The molecules can reduce or reverse Siglec-15-mediated immunosuppression, thereby increasing an immune response in a subject in need thereof.
Methods using these antibodies can inhibit or retard tumor growth, reduce tumor-mediated immune suppression, eliminate tumors, and deplete or block the activity of tumor-associated macrophages to alter their function.
Antagonistic Siglec-15 binding molecules can decrease TGF-β secretion by macrophages, reduce or reverse T cell suppression, and increase T cell proliferation.
Agonistic Siglec-15 binding molecules can decrease immune responses, increase or enhance T cell suppression, and increase TGF-β secretion by macrophages, which is beneficial for treating inflammation, autoimmune diseases, or in transplant recipients.
The antibodies can detect Siglec-15 expression in tissues or samples, enabling diagnosis, disease monitoring, and assessment of treatment responses.
Siglec-15 antagonists can reduce osteoclast differentiation, bone resorption, and increase bone formation, offering a selective therapeutic strategy for bone-related disorders.
Documented Applications
Treatment of cancer by administering Siglec-15 antibodies to retard tumor growth, inhibit tumor-mediated immune suppression, and target tumor-associated macrophages.
Treatment of infectious diseases (including acute and chronic infections) via administration of Siglec-15 antagonists to enhance immune responses.
Treatment of inflammatory and autoimmune disorders, as well as transplant rejection and graft-versus-host disease, using agonistic Siglec-15 antibodies to reduce or inhibit immune responses.
Reduction of osteoclast differentiation, bone resorption, and increase in bone formation by administration of Siglec-15 binding molecules to treat bone-related disorders.
Diagnostic and monitoring methods using Siglec-15 antibodies to detect and measure expression of Siglec-15 for disease diagnosis, monitoring progression, and evaluating treatment response.
Interested in licensing this patent?