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Method of producing a binder-toxin fusion protein in a plant cell or a whole plant

A technology for fusion proteins and plant cells, which is applied in the field of conjugate-toxin fusion proteins, and can solve the problem of difficulty in realizing the payload of active protein toxins.

Active Publication Date: 2021-11-30
ATB治疗公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0021] However, production of active protein toxin payloads or conjugates comprising the latter is difficult to achieve in mammalian cells for toxicity reasons, especially if using cleavage sites recognized by mammalian proteases

Method used

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  • Method of producing a binder-toxin fusion protein in a plant cell or a whole plant
  • Method of producing a binder-toxin fusion protein in a plant cell or a whole plant
  • Method of producing a binder-toxin fusion protein in a plant cell or a whole plant

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Embodiment

[0270] While the invention has been illustrated and described in detail in the drawings and foregoing description, such illustration and description are to be considered illustrative or exemplary and not restrictive; the invention is not limited to the disclosed embodiments. Other variations to the disclosed embodiments can be understood and effected by those skilled in the art in practicing the claimed invention, from a study of the drawings, the disclosure, and the appended claims. In the claims, the word "comprising" does not exclude other elements or steps, and the indefinite article "a" or "an" does not exclude a plurality. The mere fact that certain measures are recited in mutually different dependent claims does not indicate that a combination of these measures cannot be used to advantage. Any reference signs in the claims should not be construed as limiting the scope.

[0271] All amino acid sequences disclosed herein are shown from N-terminus to C-terminus; all nucle...

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Abstract

The present invention relates to a method of producing a binder-toxin fusion protein comprising at least, one protein binder selected from the group consisting of an antibody, an antibody fragment or derivative retaining target binding capacity, or an antibody mimetic, optionally, a peptide linker, and at least one protein toxin or protein protoxin. The method comprises the steps of: contacting a plant cell or a whole plant with a nucleic acid construct comprising in operational linkage at least the following (A) at least one polynucleotide encoding for the protein binder, or a target binding chain or domain thereof, and either B1) a polynucleotide encoding for a cleavable peptide linker and a polynucleotide encoding for a protein toxin, or B2) a polynucleotide encoding for a protein protoxin, which protoxin comprises a cleavable domain for activation thereof, allowing the construct to integrate into the nucleus of the plant cell, or of one or more cells of the whole plant, and expressing the fusion protein encoded by the nucleic acid construct (Fig. 7).

Description

[0001] field of invention [0002] The present application relates to the field of conjugate-toxin fusion proteins. Background technique [0003] Conjugates combining target binders and toxins were developed over forty years ago and now represent a major hope in the fight against cancer. These conjugates are mainly represented by the class of antibody-drug-conjugates (ADCs), consisting of a monoclonal antibody chemically conjugated to a chemical cytotoxic agent through a linker. These drugs combine the cancer cell-targeting specificity of monoclonal antibodies with the highly toxic potency of the payload to kill the targeted cells while leaving healthy tissue unharmed. [0004] However, this concept has proven difficult to translate into clinical success. Despite its specificity for tumor cells, adverse reactions often occur when the product does not reach its therapeutically effective dose, resulting in a relatively narrow therapeutic window, which may limit its clinical re...

Claims

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Application Information

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IPC IPC(8): C12N15/82C07K16/18C07K16/28
CPCC07K16/2818C07K2317/11C07K2317/24C07K2317/622C07K2317/92C07K2319/02C07K2319/50C07K2319/55C12N15/8257C12N15/8258C07K16/2887A61K2039/505C07K2317/13
Inventor B·玛吉M·乌里
Owner ATB治疗公司
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