The present invention is drawn to artificial metalloenzymes for use in cyclopropanation reactions, amination and C—H insertion.

Provided herein are methods and compositions for treating a subject suffering from a deficiency in α-L-Iduronidase in the CNS. The methods include systemic administration of a bifunctional fusion antibody comprising an antibody to a human insulin receptor and an α-L-Iduronidase. A therapeutically effective systemic dose is based on the specific CNS uptake characteristics of human insulin receptor antibody-α-L-Iduronidase fusion antibodies as described herein.

The present application provides methods, compositions and kits for determining SHD catabody levels in a biological sample, and for treating or preventing a protein aggregation disease (PAD) in an individual. Also provided are catabodies specifically recognizing amyloid beta (Aβ) peptides and methods of use thereof.

The present invention relates to a polypeptide comprising 7 β-strands A, B, C, D, E, F, and G sequentially connected together by connecting chains of amino acids, and a first α-helix sequentially located on the EF chain between β-strands E and F, wherein the β-strands are arranged so as to form a first β-sheet comprising β-strands A, B, D, and E, and a second β-sheet comprising β-strands C, F and G, said first and second β-sheets being covalently bonded together so as to form a first Ig domain; wherein the EF chain between β-strands E and F comprises the sequence X.sup.1-X.sup.2-X.sup.3-X.sup.4-K.sup.5H.sup.6 (SEQ ID NO:98), and X.sup.1, X.sup.3 and X.sup.4 are each independently any amino acid residue, characterized in that X.sup.2 is selected from the group consisting of A, G, I, V, L, R, S, T, Q, P, N, M, H, W, and pharmaceutically acceptable salts, stereoisomers, tautomers, solvates, and prodrugs thereof.

The present invention provides antibody compounds that contain a substitution of arginine for the reactive lysine residue (Lys99) in the hydrophobic cleft (38C2_Arg). The invention also provides antibody drug conjugate compounds (ADCs) that contain cargo moieties that are site-specifically conjugated to the engineered arginine residue in the 38C2_Arg variant antibody. Further provided in the invention are therapeutic applications of the compounds.

Provided herein are methods and compositions for treating a subject suffering from a deficiency in α-L-Iduronidase in the CNS. The methods include systemic administration of a bifunctional fusion antibody comprising an antibody to a human insulin receptor and an α-L-Iduronidase. A therapeutically effective systemic dose is based on the specific CNS uptake characteristics of human insulin receptor antibody-α-L-Iduronidase fusion antibodies as described herein.

A method for producing a κ light chain antibody having enzyme activity or improved enzyme activity includes modifying a polynucleotide that encodes a κ light chain antibody having a polypeptide having an amino acid sequence where the 95th amino acid residue from the N-terminal of a variable region by the Kabat classification is a proline residue, to delete or substitute the proline residue and to obtain a polynucleotide that encodes a κ light chain antibody having a polypeptide having an amino acid sequence where the 95th amino acid residue from the N-terminal of a variable region by the Kabat classification is deleted or substituted with an amino acid residue other than a proline residue, and expressing a κ light chain antibody having enzyme activity in an intracellular or extracellular expression system by using an expression vector including the polynucleotide that encodes a κ light chain antibody obtained after modification.

The present application provides methods, compositions and kits for determining SHD catabody levels in a biological sample, and for treating or preventing a protein aggregation disease (PAD) in an individual. Also provided are catabodies specifically recognizing amyloid beta (Aβ) peptides and methods of use thereof.

The present invention relates to a polypeptide comprising 7 β-strands A, B, C, D, E, F, and G sequentially connected together by connecting chains of amino acids, and a first α-helix sequentially located on the EF chain between β-strands E and F, wherein the β-strands are arranged so as to form a first β-sheet comprising β-strands A, B, D, and E, and a second β-sheet comprising β-strands C, F and G, said first and second β-sheets being covalently bonded together so as to form a first Ig domain; wherein the EF chain between β-strands E and F comprises the sequence X.sup.1-X.sup.2-X.sup.3-X.sup.4-K.sup.5H.sup.6 (SEQ ID NO:98), and X.sup.1, X.sup.3 and X.sup.4 are each independently any amino acid residue, characterized in that X.sup.2 is selected from the group consisting of A, G, I, V, L, R, S, T, Q, P, N, M, H, W, and pharmaceutically acceptable salts, stereoisomers, tautomers, solvates, and prodrugs thereof

Selective amplification of DNA in PCR exponentially increases the signal in molecular diagnostics for nucleic acids, but analogous techniques exist for signal enhancement in clinical tests for proteins or cells. Instead, the signal from affinity-based measurements of these biomolecules depends linearly on probe concentration. Substituting antibody-based probes tagged for fluorescent quantification with lasing detection probes would create a new platform for biomarker quantification based on optical rather than enzymatic amplification. Here, a viral laser is constructed which bridges synthetic biology and laser physics, and demonstrates viral-lasing probes for biosensing. At the transition to lasing, photon flux from the probes increases by five orders of magnitude and narrows spectral linewidth to below 5.0 nm. Viral-lasing probes display an unprecedented >1,000,000% increase in signal from only a 50% increase in probe concentration, using fluorimeter-compatible optics, and can detect biomolecules at clinically-relevant concentrations.