Anti-canine CD16 polypeptides, anti-canine CD64 polypeptides, compositions including same, and methods of using
Inventors
Walcheck, Bruce K. • Wu, Jianming • Vallera, Daniel A.
Assignees
University of Minnesota System
Publication Number
US-12269887-B2
Publication Date
2025-04-08
Expiration Date
2043-01-20
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Abstract
An anti-canine CD16 polypeptide generally includes a CDR region of SEQ ID NO:5, a CDR region of SEQ ID NO:9, or a functional variant of either CDR region. An anti-canine CD64 polypeptide generally includes a CDR region of SEQ ID NO:13, a CDR region of SEQ ID NO:17, or a functional variant of either CDR region. The anti-canine CD16 polypeptide and anti-canine CD64 polypeptide may be incorporated into a therapeutic compound, a multispecific compound, a targeted imaging compound, or a capture assay device.
Core Innovation
The invention described relates to anti-canine CD16 and anti-canine CD64 polypeptides, as well as multispecific compounds, targeted imaging compounds, and capture assay devices including these polypeptides. The anti-canine CD16 polypeptide includes specific complementarity-determining region (CDR) sequences such as those of SEQ ID NO:5 and SEQ ID NO:9, or functional variants, while the anti-canine CD64 polypeptide includes CDR regions of SEQ ID NO:13 and SEQ ID NO:17, or their functional variants. These polypeptides can be used individually or as part of more complex constructs to enable selective binding to canine CD16A or CD64 proteins.
The invention addresses the problem of studying and therapeutically exploiting Fc gamma receptors in dogs, which is hindered by the lack of species-specific antibodies and tools for canine CD16A and CD64. These receptors play crucial roles in antibody-dependent cellular cytotoxicity (ADCC) and immunotherapy, but current models using other species are limited due to significant immune differences.
The core innovation involves generating monoclonal antibodies and polypeptides specifically targeting canine CD16A and CD64, characterizing their binding and functionality, and incorporating them into versatile platforms. These platforms include chimeric antigen receptor therapies, multispecific immune cell engagers, targeted immunotherapies, and devices for diagnostic or capture purposes. The invention further enables the development of therapeutic agents that induce NK cell-mediated killing, diagnostics using targeted imaging, and capture assay devices for canine immune research and treatment.
Claims Coverage
The patent claims a total of six main inventive features based on the independent claims.
Anti-canine CD16 polypeptide comprising specified CDR sequences
This feature covers an anti-canine CD16 polypeptide that comprises SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 10, DTS (SEQ ID NO:11), and SEQ ID NO:12. This polypeptide includes regions derived from the variable regions of antibodies specific to canine CD16.
Anti-canine CD64 polypeptide comprising specified CDR sequences
This feature covers an anti-canine CD64 polypeptide that comprises SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:19, and SEQ ID NO:20. The polypeptide includes regions from monoclonal antibodies specific to canine CD64.
Multispecific compound with anti-canine CD16 polypeptide as immune cell engaging domain
This feature covers multispecific compounds comprising: - A targeting domain that selectively binds to a target cell or target antigen expressed by a target cell - An immune cell engaging domain operably linked to the targeting domain, with the immune cell engaging domain comprising an anti-canine CD16 polypeptide as defined above (SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:10, DTS, SEQ ID NO:12).
Multispecific compound with anti-canine CD64 polypeptide as immune cell engaging domain
This feature covers multispecific compounds comprising: - A targeting domain that selectively binds to a target cell or target antigen expressed by a target cell - An immune cell engaging domain operably linked to the targeting domain, where the immune cell engaging domain comprises an anti-canine CD64 polypeptide (SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20).
Targeted imaging compound including anti-canine CD16 or CD64 polypeptide
This feature covers targeted imaging compounds comprising: - A targeting domain that includes either the anti-canine CD16 or anti-canine CD64 polypeptide as defined - An imaging domain linked to the targeting domain, where the imaging domain can be a colorimetric, fluorescent, radioactive, magnetic, or enzymatic label.
Capture assay device incorporating anti-canine CD16 or CD64 polypeptide
This feature covers a capture assay device comprising the anti-canine CD16 or CD64 polypeptide immobilized to a substrate for the purpose of capturing or detecting respective targets.
In summary, the patent covers anti-canine CD16 and CD64 polypeptides defined by specific CDR sequences, their use as immune cell engaging domains in multispecific compounds, application in targeted imaging constructs, and their integration into capture assay devices.
Stated Advantages
Enables development of species-specific antibodies and tools for canine CD16A and CD64, overcoming the lack of reagents for studying and targeting these receptors in dogs.
Facilitates the engineering of multispecific compounds and therapeutic agents to induce NK cell-mediated cytotoxicity in canine models and potentially improve cancer immunotherapy.
Allows use of dogs as clinically relevant disease models with comparable immune systems for studying human immunotherapies.
Permits development of targeted imaging and capture assay platforms using anti-canine CD16 or CD64 polypeptides.
Documented Applications
Use in chimeric antigen receptor therapies, including CAR-NK therapy, CAR-T therapy, and CAR-macrophage therapy.
Application in multispecific immune cell engager technologies, such as bispecific and trispecific killer engagers or T cell engagers.
Deployment in targeted immunotherapies, such as targeted ADAM17 blocker therapies.
Use in delivery of therapeutics, including antibody-drug conjugates, delivery of therapeutic radioisotopes, toxins, cytokines, or chemokines.
Functionality in imaging technologies by delivering labeling constructs or radioisotopes for targeted imaging.
Application in cell and/or ligand capture technologies such as ELISA and related assay devices.
Treatment of subjects (including canines and humans) for cancers in which tumor cells express a tumor antigen, including prostate cancer, lung cancer, colon cancer, rectum cancer, urinary bladder cancer, melanoma, kidney cancer, renal cancer, oral cavity cancer, pharynx cancer, pancreas cancer, uterine cancer, thyroid cancer, skin cancer, head and neck cancer, cervical cancer, ovarian cancer, osteosarcoma, or hematopoietic cancers.
Treatment or prevention of infectious conditions in which infected cells express an infectious antigen.
Use as targeted imaging compounds for detection based on colorimetric, fluorescent, radioactive, magnetic, or enzymatic labels.
Use as capture assay devices by immobilizing the polypeptide to capture and detect CD16 or CD64 in samples.
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