A surfactant for a bioconjugation reaction is disclosed, wherein a biomolecule comprising one or more azide moieties is connected to an cyclic alkyne comprising payload. More specifically, the invention concerns a method for the preparation of a bioconjugate of structure B—(Z—L—D).sub.x (1), comprising reacting (i) an alkyne or alkene compound of structure Q—L—D (2), wherein Q is a click probe comprising a cyclic alkyne moiety or a cyclic alkene moiety, L is a linker, and D is a payload; with (ii) a molecule of structure B—(F).sub.x (3), wherein B is a biomolecule that is functionalized with x click probes F; F is a click probe capable of reacting with Q, and x is an integer in the range of 1-10, in presence of a surfactant.

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload inhibits activity of a disease allele associated with muscle disease. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide or RNAi oligonucleotide.

The present invention is directed to dosing regimens for administering a humanized anti-B7-H3 antibody conjugated to at least one duocarmycin moiety (a “B7-H3-ADC”) for the treatment of cancer, particularly a cancer associated with expression of B7-H3. The invention particularly concerns the use of such B7-H3-ADC optionally in combination with a PD-1 binding molecule for the treatment of cancer. The invention particularly concerns the use of such B7-H3-ADC and an anti-PD-1 antibody or a PD-1 X LAG-3 bispecific molecule. The invention is directed to the use of such molecules, and to the use of pharmaceutical compositions and pharmaceutical kits that contain such molecules and that facilitate the use of such dosing regimens in the treatment of cancer.

Antibody drug conjugates (ADC's) that bind to 191P4D12 protein and variants thereof are described herein. 191P4D12 exhibits tissue specific expression in normal adult tissue, and is aberrantly expressed in the cancers listed in Table I. Consequently, the ADC's of the invention provide a therapeutic composition for the treatment of cancer.

A camptothecin drug having a highly stable hydrophilic connecting unit and its conjugate, or its pharmaceutically acceptable salt thereof, including methods for preparation thereof, and its applications in preventing and/or treating cancer. The conjugate can specifically bind to receptors highly expressed in tumor cells. The conjugates have excellent water solubility, stability, and homogeneity, and can be used for preventing and/or treating tumors and/or other diseases.

Sulfonamide-containing linkage systems for release of payload compounds from an attached targeting moiety in drug conjugates. The conjugates have the formula of [(P)-(L)]m-(T), wherein (P) is a payload compound, (L) is a linker, (T) is a targeting moiety and m is an integer from 1- to 10. Also provided are pharmaceutical compositions comprising such conjugates and there use in treating cancer.

This disclosure provides compositions and methods for delivering a viral composition to cells, e.g., for cell surface receptor-mediated uptake, and enhanced viral transduction. Viral transduction can be achieved via a bifunctional bridging composition that includes a moiety that binds to a cell surface receptor ligand and a linked bridging moiety that binds to a viral composition. Also provided are modified viral compositions comprising a bridging composition specifically bound via its bridging moiety to the viral composition. Modified viral compositions and methods for reducing levels or titers of neutralizing antibodies in a subject in need of viral therapy, e.g., gene therapy, are provided. In some embodiments, the modified viral composition includes empty viral particles that bind and internalize neutralizing autoantibodies. Modified viral compositions including empty viral particles can be administered prior to viral therapy. Also provided are pharmaceutical compositions and kits including a bifunctional bridging composition and/or modified viral compositions.

This document provides methods and materials involved in treating cancer. For example, methods and materials for using a BiPE that can include (a) one or more molecules having the ability to bind to a cancer cell (e.g., a human breast cancer cell), (b) an optional linker component, and (c) one or more molecules having the ability to bind to an antigen presenting cell (e.g., a human macrophage) to treat cancer are provided.

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload inhibits expression or activity of DUX4. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide or RNAi oligonucleotide.

The current invention describes a conjugate of a targeting moiety linked to a drug via a molecule having high affinity for the targeting moiety at physiological pH such that the drug releases at low pH from the targeting moiety.