Targeting treatment for ADAM30 in pathological cells
Inventors
Tan, Wenbin • Taine, Elaine G. • Wang, Hui • Nguyen, Vi • Cao, Xiaoling
Assignees
Publication Number
US-12006550-B2
Publication Date
2024-06-11
Expiration Date
2041-08-12
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Abstract
Described herein are methods and systems using ADAM30 as a biomarker to help early diagnosis of congenital malformed vasculatures in children and which can also serve as a companion diagnostic biomarker for malformed vasculatures, as well as a subpopulation of cancer cells, wherein blockage of activity of ADAM30 by a neutralized antibody or inhibitor can be used as a treatment strategy for those ADAM30-positive vascular endothelial cells and cancer cells.
Core Innovation
The invention provides methods and systems utilizing ADAM30 as a biomarker for the early diagnosis of congenital malformed vasculatures in children, serving also as a companion diagnostic biomarker for malformed vasculatures and certain subpopulations of cancer cells. Detecting the presence of ADAM30 in body fluids, such as blood, CSF, or urine, enables correlation with congenital vascular malformations or identification of specific cancer cell subtypes. The biomarker is characterized by a genetic sequence, SEQ ID NO.: 1, and is a member of the disintegrin and metalloproteinase family.
The invention addresses the problem of inadequate early diagnostic tools and limited treatment options for congenital vascular malformations, such as Sturge-Weber Syndrome and cerebral vascular malformations, due to the lack of reliable biomarkers. Existing treatments are challenged by the complexity of the involved vascular types and symptom severity, leading to difficulties in diagnosis and management, with variable prognoses and unsatisfactory outcomes.
The invention also provides a novel therapeutic strategy: blocking ADAM30 activity in ADAM30-positive vascular endothelial cells and cancer cells by administering a neutralized antibody or inhibitor. These approaches enable the treatment of diseases associated with aberrant ADAM30 expression or activity, representing the first targeting therapy for such disorders using this biomarker-driven method.
Claims Coverage
The patent contains one independent claim which introduces three main inventive features that center on the detection of vascular malformations through an antibody-based assay targeting ADAM30, and the diagnostic decision-making for subsequent therapy.
Detection of congenital vascular malformations using an antibody-based assay for ADAM30 biomarker in body fluids
A method that includes obtaining at least one body fluid sample from a subject and introducing at least one human or humanized antibody with at least two binding specificities for at least two different antigens. The antibody is configured to bind to at least one domain of a biomarker comprising an ADAM30 protein or polypeptide present in the body fluid. The method covers in vivo or in vitro analysis, where antibody binding to the biomarker forms an assay. The detection of the biomarker's presence in the sample indicates a vascular disease or disorder associated with aberrant ADAM30 expression or activity in the subject.
Use of multi-specific human or humanized antibodies for binding to ADAM30 domains as part of the detection assay
The inventive feature specifies that the antibody used has at least two binding specificities for at least two different antigens, allowing it to target at least one domain of the ADAM30 biomarker. This design enhances specificity in identifying the presence of ADAM30 protein or polypeptide in the body fluid sample.
Therapeutic decision based on ADAM30 biomarker assay for administering treatment
The method determines that an increase in ADAM30, as identified by the antibody-based assay, serves as the trigger point to administer a therapeutically effective amount of a therapeutic agent to treat the vascular disease or disorder. Formation of the assay thus links biomarker detection directly to treatment decision-making.
Collectively, the independent claim covers methods for detecting congenital vascular malformations by leveraging a multi-specific human or humanized antibody assay for ADAM30 in body fluids, using this detection as the criterion for therapeutic intervention.
Stated Advantages
Enables early diagnosis of congenital vascular malformations, such as Sturge-Weber Syndrome, by using ADAM30 as a biomarker detectable in body fluids.
Provides a companion diagnostic biomarker for identifying malformed vasculatures and certain subpopulations of cancer cells.
Introduces the first targeting treatment option for congenital vascular malformations by neutralizing ADAM30 activity.
Offers a novel, biomarker-driven approach to enhance treatment efficacy for ADAM30-positive vascular endothelial and cancer cells.
Documented Applications
Early diagnosis of congenital malformed vasculatures in children, including identification of Sturge-Weber Syndrome.
Differentiation of cancer cell subtypes using ADAM30 as a biomarker.
Companion diagnostic for malformed vasculatures and a subset of cancer cells.
Therapeutic treatment strategy for ADAM30-positive vascular endothelial cells and cancer cells via neutralized antibody or inhibitor.
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