The present invention provides a human-derived molecularly modified insecticidal protein, and a preparation method and application thereof, and belongs to the field of genetic engineering and biological control. The present invention provides a human-derived molecularly modified insecticidal protein, and the amino acid sequence of the insecticidal protein CCL-CCL_scFv is shown as SEQ ID No.1. The insecticidal protein CCL-CCL_scFv shows significantly higher affinity with midgut BBMV of Plutella xylostella than Cry1Ab toxin, competes with Cry1Ab and Cry1Ac toxins for binding the midgut BBMV of Plutella xylostella, and is a mimic of Cry1Ab and Cry1Ac toxins. Through Plutella xylostella indoor insecticidal biological activity assay, the insecticidal protein shows a good insecticidal effect, and can effectively replace Cry1Ac or Cry1Ab toxin for biological control of insect pest.

Provided herein are DLL3 binding proteins and DLL3 targeting multispecific proteins (e.g., DLL3 targeting trispecific protein) comprising a domain binding to CD3, a half-life extension domain, and a domain binding to DLL3 (such as a DLL3 binding protein as provided herein). Also provided are pharmaceutical compositions thereof, as well as nucleic acids, recombinant expression vectors and host cells for making such DLL3 binding proteins, DLL3 targeting trispecific proteins. Also disclosed are methods of using the disclosed DLL3 binding proteins, DLL3 targeting trispecific proteins in the prevention, and/or treatment diseases, conditions and disorders.

The invention provides novel biparatopic LRP5/LRP6 cross-reactive binding polypeptides, and more specifically novel biparatopic LRP5/LRP6 cross-reactive immunoglobulin single variable domain constructs which can inhibit Wnt signaling pathways. The invention also relates to specific sequences of such polypeptides, methods of their production, and methods of using them, including methods of treatment of diseases such as cancer.

The invention relates to antibodies, antibody fragments and binding agents that specifically recognize oligomeric tau but do not bind to monomelic tau, fibrillar tau or non-disease associated forms of tau.

This invention relates to novel hetero-dimeric multi-specific format of multiple antibody variable domains comprising a core of two split variable domain pairs wherein both variable light domains and the two cognate variable heavy domains are positioned in tandem on two separate protein chains, respectively.

The present invention pertains to antigen recognizing constructs against tumor associated antigens (TAA), in particular the TAA Serine protease inhibitor Kazal-type 2 (SPINK2). The invention in particular provides novel T cell receptor (TCR) based molecules which are selective and specific for the tumor expressed antigen of the invention. The TCR of the invention, and SPINK2 binding fragments derived therefrom, are of use for the diagnosis, treatment and prevention of SPINK2 expressing cancerous diseases. Further provided are nucleic acids encoding the antigen recognizing constructs of the invention, vectors comprising these nucleic acids, recombinant cells expressing the antigen recognizing constructs and pharmaceutical compositions comprising the compounds of the invention.

Trispecific antigen-binding proteins including: a first binding domain capable of binding to a cell surface protein of a tumor cell; a second binding domain capable of binding to a cell surface immune checkpoint protein of the tumor cell; and a third binding domain capable of binding to a cell surface protein of an immune cell, are provided. Methods of making trispecific antigen-binding proteins are provided.

The present application provides activatable antibodies comprising an antibody comprising an antigen-binding domain (ABD), wherein the ABD comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the N-terminus of the VH is fused to a first polypeptide shield moiety (S1), and the N-terminus of the VL is fused to a second polypeptide shield moiety (S2), wherein S1 comprises a first disease-sensing releasable moiety (DS1) and/or S2 comprises a second disease-sensing releasable moiety (DS2), wherein association of S1 with S2 blocks binding of the ABD to its target, and wherein the ABD does not specifically bind to S1, S2, or association thereof. Composition, methods of treatment using the activatable antibodies, and methods of preparation thereof are further provided.

A multivalent antibody fusion protein which comprises an immunoglobulin moiety, for example a Fab or Fab fragment, with a first specificity for an antigen of interest, and further comprises two single domain antibodies (dAb) with specificity for a second antigen of interest, wherein the two single domain antibodies are linked by a disulfide bond. There is also provided particular dual specificity antibody fusion proteins comprising a Fab or Fab fragment and one or more single domain antibodies which may be stabilised by a disulfide bond therebetween.

The invention provides antibodies that bind to multiple antigens, said antibodies having at least two antibody light chain variable domains and two antibody heavy chain variable domains, wherein each light chain variable domain is linked to a heavy chain variable domain to form a VH/VL construct, and wherein at least one of the VH domains comprises a particular amino acid at AHo position 12, 103 and/or 144, and at least one of the VL domains comprises a particular amino acid at AHo position 47 and/or 50. Nucleic acid molecules, vectors and host cells for expression of the recombinant antibodies of the invention, methods for isolating them, and the use of said antibodies in medicine are also disclosed.