Anti-CD276 antibodies (B7H3)
Inventors
Dimitrov, Dimiter S. • Zhu, Zhongyu • St. Croix, Bradley • Seaman, Steven • Saha, Saurabh • Zhang, Xiaoyan Michelle • DeCrescenzo, Gary A. • WELSCH, Dean
Assignees
Biomed Valley Discoveries Inc • US Department of Health and Human Services
Publication Number
US-10604582-B2
Publication Date
2020-03-31
Expiration Date
2035-09-16
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Abstract
Polypeptides and proteins that specifically bind to and immunologically recognize CD276 are disclosed. Chimeric antigen receptors (CARs), anti-CD276 binding moieties, nucleic acids, recombinant expression vectors, host cells, populations of cells, pharmaceutical compositions, and conjugates relating to the polypeptides and proteins are also disclosed. Methods of detecting the presence of (a) cancer or (b) tumor vasculature in a mammal and methods of (a) treating or preventing cancer or (b) reducing tumor vasculature in a mammal are also disclosed.
Core Innovation
The invention provides polypeptides and proteins that specifically bind to and immunologically recognize CD276 (also known as B7-H3). These polypeptides and proteins include chimeric antigen receptors (CARs), anti-CD276 binding moieties, nucleic acids, recombinant expression vectors, host cells, populations of cells, pharmaceutical compositions, and conjugates related to these polypeptides and proteins. The inventive polypeptides and proteins specifically recognize and bind to CD276 with high affinity, including soluble CD276 and CD276 expressed on cell surfaces, and thus target CD276-expressing cancer cells and tumor vasculature.
The problem being addressed is an unmet need for improved treatments for cancer, particularly solid tumors, which remain a significant public health concern with poor prognosis despite advances like chemotherapy. CD276 is expressed or overexpressed on a variety of human tumors and tumor vasculature, serving as a tumor endothelial marker. By specifically targeting CD276, the invention aims to detect, treat, or prevent cancer, including reducing or eliminating tumor vasculature, facilitating immune cell infiltration, and enhancing anti-cancer and anti-tumor vasculature responses, thereby providing novel therapeutic and diagnostic modalities for cancer.
Claims Coverage
The patent includes multiple independent claims covering polypeptides, proteins, conjugates, nucleic acids, recombinant vectors, host cells, pharmaceutical compositions, kits, and methods related to anti-CD276 binding entities, defining their structure and use.
Polypeptides specifically binding to CD276
Polypeptides comprising heavy and light chain complementarity determining regions (CDRs) with specified amino acid sequences (SEQ ID NOs: 1-6, 11-16, or 20-25) that specifically bind to CD276.
Proteins comprising paired polypeptide chains with CD276-specific CDRs
Proteins comprising a first polypeptide chain with CDRs of SEQ ID NOs: 1-3, 11-13, or 20-22 and a second polypeptide chain with CDRs of SEQ ID NOs: 4-6, 14-16, or 23-25, specifically binding to CD276.
Anti-CD276 binding moieties including various antibody formats
Anti-CD276 binding moieties comprising the specified polypeptides, which can be antibodies, Fab fragments, F(ab')2 fragments, diabodies, triabodies, tetrabodies, single-chain variable region fragments (scFv), or disulfide-stabilized variable region fragments (dsFv).
Conjugates of anti-CD276 polypeptides or proteins with effector molecules
Conjugates comprising the anti-CD276 polypeptides or proteins conjugated to effector molecules including pyrrolobenzodiazepine (PBD) dimers, drugs, toxins, labels, small molecules, antibodies, or monomethyl auristatin E (MMAE).
Site-specific conjugation of polypeptides to effector molecules
Anti-CD276 polypeptides or binding moieties conjugated to effector molecules via site-specific conjugation methods.
Nucleic acids encoding anti-CD276 polypeptides or proteins
Nucleic acids comprising nucleotide sequences encoding the polypeptides or proteins with specified variable regions and CDRs as detailed in SEQ ID NOs: 53-58.
Recombinant expression vectors and host cells
Recombinant expression vectors comprising the nucleic acids encoding the anti-CD276 polypeptides or proteins, and host cells comprising these vectors.
Pharmaceutical compositions comprising the anti-CD276 polypeptides or proteins
Pharmaceutical compositions containing the anti-CD276 polypeptides or proteins along with pharmaceutically acceptable carriers.
Kits for treating cancer or reducing tumor vasculature
Kits comprising the anti-CD276 polypeptides, proteins, or conjugates for use in treating cancer or reducing tumor vasculature.
Methods of detecting cancer or tumor vasculature using anti-CD276 polypeptides or proteins
Methods involving contacting a sample from a mammal with the anti-CD276 polypeptides or proteins to form a complex and detecting the complex, indicative of the presence of cancer or tumor vasculature.
The claims comprehensively cover compositions of matter including anti-CD276 polypeptides, proteins, their conjugates, nucleic acids, vectors, and cells, as well as pharmaceutical preparations and kits, and methods of detecting and treating cancer or tumor vasculature, focusing on specific CDR sequences and their functional embodiments.
Stated Advantages
The polypeptides and proteins exhibit high affinity and specificity in recognizing CD276 expressed on cancer cells and tumor vasculature.
They enable targeted detection and therapy of CD276-expressing cancers and tumor vasculature, providing advantages in precision treatment.
The CARs elicit antigen-specific immune responses capable of targeting and destroying CD276-expressing tumor cells and vasculature, enhancing anti-cancer effects.
Conjugates allow delivery of cytotoxic drugs selectively to CD276-expressing cells, improving therapeutic specificity and efficacy.
Documented Applications
Detecting the presence of cancer or tumor vasculature in a mammal.
Treating or preventing cancer, including various solid tumors and adult carcinomas that express or overexpress CD276.
Reducing or eliminating tumor vasculature in a mammal.
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