A reagent kit comprising a first polypeptide including a part in any one of amino acid sequences (A) to (C), and a second polypeptide including a part in any one of amino acid sequences (A) to (C), which are consistent of different sequences from a sequence of the first polypeptide; (A) an amino acid sequence in SEQ ID NO: 1 with deletion of an amino acid sequence from position 1 to 69 and an amino acid sequence from position 204 to 221, (B) an amino acid sequence in SEQ ID NO: 1 with deletion of an amino acid sequence from position 1 to 69 and deletion or substitution of at least one of amino acid residues at positions 146 to 156, (C) the amino acid sequence (A) or (B) with further deletion of at least one of amino acid residues at positions 70 to 74.

A reagent kit comprising a first polypeptide including a part in any one of amino acid sequences (A) to (C), and a second polypeptide including a part in any one of amino acid sequences (A) to (C), which are consistent of different sequences from a sequence of the first polypeptide; (A) an amino acid sequence in SEQ ID NO: 1 with deletion of an amino acid sequence from position 1 to 69 and an amino acid sequence from position 204 to 221, (B) an amino acid sequence in SEQ ID NO: 1 with deletion of an amino acid sequence from position 1 to 69 and deletion or substitution of at least one of amino acid residues at positions 146 to 156, (C) the amino acid sequence (A) or (B) with further deletion of at least one of amino acid residues at positions 70 to 74.

Provided herein are hierarchical protein structures comprising two or more proteins extending in one or more dimensions, the hierarchical protein structure comprising: a first protein comprising: (i) a patch A comprising one or more polynucleotides conjugated to the surface of the first protein; and (ii) a patch B comprising one or more polynucleotides conjugated to the surface of the first protein; and a second protein comprising: (i) a patch A′ comprising one or more polynucleotides conjugated to the surface of the second protein; and (ii) a patch B′ comprising one or more polynucleotides conjugated to the surface of the second protein; wherein the one or more polynucleotides of the patch A hybridizes to the one or more polynucleotides of the patch A′, and/or the one or more polynucleotides of the patch B hybridizes to the one or more polynucleotides of the patch B′ to form the hierarchical protein structure. Also provided are methods of making the hierarchical protein structures.

The invention relates to novel benzodiazepine derivatives with antiproliferative activity and more specifically to novel benzodiazepines of formula (I) and (II), in which the diazepine ring (B) is fused with a heterocyclic ring (CD), wherein the heterocyclic ring is bicyclic or a compound of formula (III), in which the diazepine ring (B) is fused with a heterocyclic ring (C), wherein the heterocyclic ring is monocyclic. The invention provides cytotoxic dimers of these compounds. The invention also provides conjugates of the monomers and the dimers. The invention further provides compositions and methods useful for inhibiting abnormal cell growth or treating a proliferative disorder in a mammal using the compounds or conjugates of the invention. The invention further relates to methods of using the compounds or conjugates for in vitro, in situ, and in vivo diagnosis or treatment of mammalian cells, or associated pathological conditions.

The invention relates to novel benzodiazepine derivatives with antiproliferative activity and more specifically to novel benzodiazepines of formula (I) and (II), in which the diazepine ring (B) is fused with a heterocyclic ring (CD), wherein the heterocyclic ring is bicyclic or a compound of formula (III), in which the diazepine ring (B) is fused with a heterocyclic ring (C), wherein the heterocyclic ring is monocyclic. The invention provides cytotoxic dimers of these compounds. The invention also provides conjugates of the monomers and the dimers. The invention further provides compositions and methods useful for inhibiting abnormal cell growth or treating a proliferative disorder in a mammal using the compounds or conjugates of the invention. The invention further relates to methods of using the compounds or conjugates for in vitro, in situ, and in vivo diagnosis or treatment of mammalian cells, or associated pathological conditions.

A method for improving a bio-coupling efficiency between a protein and a nucleic acid based on an α-helix handle includes the following steps. First, the handle carrying the non-natural amino acid (H-tag) is designed. Then, a recombinant expression plasmid encoding a fusion protein containing the H-tag and the protein to be tested is constructed. Subsequently, the fusion recombinant protein containing the non-natural amino acid in the H-tag is expressed and purified. Finally, the non-natural amino acid in the H-tag-fused protein and the coupling group on the nucleic acid substrate are efficiently connected by click chemistry. Thea-helix handle is used to provide a controllable reaction condition on the protein surface for the non-natural amino acid, avoiding the complex structure, charge and polar nanoenvironment around the surface of the protein to be tested.

A method for improving a bio-coupling efficiency between a protein and a nucleic acid based on an α-helix handle includes the following steps. First, the handle carrying the non-natural amino acid (H-tag) is designed. Then, a recombinant expression plasmid encoding a fusion protein containing the H-tag and the protein to be tested is constructed. Subsequently, the fusion recombinant protein containing the non-natural amino acid in the H-tag is expressed and purified. Finally, the non-natural amino acid in the H-tag-fused protein and the coupling group on the nucleic acid substrate are efficiently connected by click chemistry. Thea-helix handle is used to provide a controllable reaction condition on the protein surface for the non-natural amino acid, avoiding the complex structure, charge and polar nanoenvironment around the surface of the protein to be tested.

The present invention is directed to novel targeted heterodimeric fusion proteins comprising an IL-15/IL-15Rα Fc-fusion protein and a TIM-3 antibody fragment-Fc fusion protein.

The present invention is directed to novel targeted heterodimeric fusion proteins comprising an IL-15/IL-15Rα Fc-fusion protein and a TIM-3 antibody fragment-Fc fusion protein.

Provided herein are protein-based purification matrices and methods of use thereof to purify biologics and/or to remove contaminants from a composition. Methods of bringing two or more biologics in close proximity are also provided. The disclosed compositions and methods allow for faster, more efficient purification of a biologic compared to traditional affinity chromatography.