Anti-EDB antibodies and antibody-drug conjugates
Inventors
HOOPER, Andrea Therese • Marquette, Kimberly Ann • Subramanyam, Chakrapani • Gerber, Hans-Peter • MAY, Chad Michael
Assignees
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Publication Number
US-12636377-B2
Publication Date
2026-05-26
Expiration Date
Abstract
The present invention provides antibodies and antibody-drug conjugates that bind to the extra domain B splice variant of fibronectin 1 and methods for preparing and using the same.
Core Innovation
The disclosure relates to polynucleotides encoding antibodies and antigen-binding fragments that specifically bind extra domain B of fibronectin. The compositions include anti-EDB antibodies and antibody-drug conjugates featuring cleavable or non-cleavable linkers with cytotoxic or imaging payloads, utilizing conventional or site-specific conjugation [procedural detail omitted for safety]. In preclinical tumor and cell models, these targeted binding molecules mediate selective cellular cytotoxicity and inhibit tumor growth across multiple human cancer types.
The disclosure further provides nucleic acids encoding antibody chains, expression vectors, host cells, and methods for producing the binding molecules or conjugates [procedural detail omitted for safety]. Reported evaluations demonstrate dose-dependent tumor inhibition or regression across xenograft and syngeneic models. In addition, site-specific conjugates exhibit improved systemic exposure, enhanced conjugation stability, favorable thermal stability, and reduced neutropenia compared to conventional conjugates.
Claims Coverage
The claims comprise two independent claims directed to polynucleotides encoding EDB-binding antibodies or antigen-binding fragments, along with dependent claims covering vectors, host cells, and production methods, totaling five inventive features.
Polynucleotide encoding an EDB-binding antibody with specified variable regions
An independent claim covers a polynucleotide encoding an antibody or antigen-binding fragment that binds extra domain B of fibronectin and comprises specified heavy-chain and light-chain variable regions [procedural detail omitted for safety].
Polynucleotide encoding an EDB-binding antibody with specified chain sequences
An independent claim covers a polynucleotide encoding the heavy-chain or light-chain region of an antibody or antigen-binding fragment that binds extra domain B of fibronectin, comprising specified chain sequences [procedural detail omitted for safety].
Vector comprising the polynucleotide
A dependent claim covers a vector comprising the claimed polynucleotide [procedural detail omitted for safety].
Isolated host cell comprising the vector
A dependent claim covers an isolated host cell comprising the vector [procedural detail omitted for safety].
Production using the isolated host cell
A dependent claim covers a method of producing the antibody or antigen-binding fragment using the isolated host cell [procedural detail omitted for safety].
The claims encompass polynucleotides encoding EDB-binding antibodies or antigen-binding fragments defined by specified heavy- and light-chain regions, and extend to vectors, isolated host cells, and methods of producing the binding molecules.
Stated Advantages
EDB-targeting antibody-drug conjugates produce dose-dependent tumor inhibition or regression in reported tumor models, including durable complete regressions in certain cohorts.
Site-specific conjugated EDB antibody-drug conjugates exhibit improved exposure, enhanced conjugation and thermal stability, increased homogeneity, favorable pharmacokinetics, and substantially reduced neutropenia compared with conventional conjugates.
Tumor assays demonstrate preferential tumor accumulation as well as markers of mitotic arrest and apoptosis following EDB antibody-drug conjugate treatment.
Documented Applications
Cancer treatment and imaging applications targeting EDB-expressing malignancies, with expression profiled across human pancreatic, lung, breast, and ovarian cancers.
Evaluation of binding, selective cell killing, and tumor-volume responses in xenograft, patient-derived xenograft, lymphoma, and syngeneic tumor models, including H-1975, HT29, PDX, Ramos, and EMT-6 models.
Assessment of neutrophil counts and neutropenia profiles following administration of EDB-L19-vc-0101 and comparator antibody-drug conjugates.
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