Recombinant, single-chain, trivalent tri-specific or bi-specific antibody derivatives

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This invention describes recombinant, single-chain antibody derivatives that are either tri-specific or bi-specific, meaning they can bind three (or two) different antigens simultaneously. These molecules are designed to target tumor cells, including tumor stem cells, with two binding domains while the third domain binds to antigens present on immune effector cells (such as NK cells, monocytes, neutrophils, or macrophages). By ensuring at least a 2:1 ratio in favor of tumor-cell targeting, the antibodies preferentially bind to tumor cells first, enhancing the specificity and efficiency of immune-mediated tumor cell destruction. The technology also includes methods for producing these antibodies and compositions for diagnostic and therapeutic (anti-tumor) applications.

Use CasesContent extracted from patent full text and abstract with AI.

• Targeted immunotherapy for leukemia or lymphoma, especially those resistant to standard treatments.
• Selective elimination of tumor stem cells or progenitor cells to prevent relapse in cancer patients.
• Development of bioengineered antibody drugs with enhanced specificity for clinical oncology.
• Detection and diagnosis of cancers by tagging malignant cells in vitro or in vivo.
• Combination immunotherapy alongside other chemotherapy or biological agents for hematological malignancies.

BenefitsContent extracted from patent full text and abstract with AI.

• Improved targeting of tumor cells versus normal cells, reducing off-target effects and toxicity.
• Enhanced immune cell recruitment and activation at the tumor site, boosting anti-tumor efficacy.
• Minimizes untargeted immune effector cell activation, lowering adverse immune reactions.
• Higher affinity and avidity for tumor cells due to multivalency and optimized binding site ratio.
• Greater molecular stability and predictable production as single-chain constructs, facilitating manufacturing and reducing immunogenicity.

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Inventors & Applicants

Patent Abstract

The present invention relates to a nucleic acid molecule encoding a polypeptide, wherein the polypeptide comprises (a) a first immunoglobulin domain comprising a V L domain linked to a V H domain, wherein the immunoglobulin domain specifically binds to an antigen expressed on tumour cells; (b) a second immunoglobulin domain comprising a V L domain linked to a V H domain, wherein the immunoglobulin domain specifically binds to an antigen expressed on tumour cells; and (c) a third immunoglobulin domain comprising a V L domain linked to a V H domain, wherein the immunoglobulin domain specifically binds to an effector cell antigen, wherein the effector cell is selected from the group consisting of NK cells, neutrophilic granulocytes, monocytes and macrophages; wherein at least one of the antigens expressed on tumour cells and bound by the immunoglobulin domain of (a) or (b) is an antigen expressed on tumour stem cells and/or on tumour precursor or progenitor cells; and wherein the ratio of immunoglobulin domains binding to antigens expressed on tumour cells and those binding to effector cell antigens is at least 2:1. The present invention furthermore relates to a vector comprising the nucleic acid molecule of the invention, a non-human host transformed with the vector of the invention, a method of producing a polypeptide comprising culturing the host of the invention under suitable conditions and isolating the polypeptide produced and a polypeptide encoded by the nucleic acid molecule of the invention or produced by the method of the invention. In addition, the present invention relates to diagnostic and pharmaceutical compositions and methods for treating tumours.