The invention relates to novel methods for synthesizing amanitin derivatives having a hydroxy group attached to the central tryptophan moiety. The invention furthermore relates to novel amanitin derivatives having a hydroxy group attached to position 4′, 5′ or 7′ of the central tryptophan moiety, novel conjugates of such amanitin derivatives, and pharmaceutical compositions comprising such conjugates.

The invention provides methods of preventing and treating graft-versus-host-disease, such as those arising from transplant therapy, by selective depletion of hematopoietic cells through the use of antibodies, antibody fragments, and antibody-drug conjugates that specifically bind CD252. The compositions and methods described herein can be used to treat a variety of pathologies, including stem cell disorders and other blood conditions.

The invention provides methods of preventing and treating graft-versus-host-disease and autoimmune diseases, such as those arising from transplant therapy, by selective depletion of hematopoietic cells through the use of antibody-drug conjugates (ADCs) that specifically bind CD134 or CD278. The compositions and methods described herein can be used to treat a variety of pathologies, including autoimmune diseases, stem cell disorders, and other blood conditions.

A bicyclic octapeptide derivative is conjugated to a corresponding target-binding group by a special chemical structure. The structure of the derivative is stable in blood plasma and decomposes into a drug as an active ingredient in a specific biological environment, thereby maximizing killing effect on target cells and minimizing toxic side effects on non-target cells. The derivative can be used in the treatment of various malignant tumors.

The invention relates generally to antibodies, activatable antibodies, multispecific antibodies, and multispecific activatable antibodies that specifically bind to at least CD3, as well as to methods of making and using these antibodies, activatable antibodies, multispecific antibodies, and/or multispecific activatable antibodies in a variety of therapeutic, diagnostic and prophylactic indications.

The invention relates to novel methods for synthesizing amanitin derivatives having an amino group attached to position 6 of the central tryptophan moiety. The invention furthermore relates to a novel amanitin derivative having an amino group attached to position 6 of the central tryptophan moiety, novel conjugates of such amanitin derivative, and pharmaceutical compositions comprising such conjugates.

The present invention relates to an amatoxin-linker construct comprising an amatoxin according to formula (I) wherein: R.sub.1 and R.sub.2 are each OH, R3 is NH.sub.2, or a linker which carries a reactive group Y for linking said amatoxin to a target-binding moiety, R.sub.4 is H or a linker which carries a reactive group Y for linking said amatoxin to a target-binding moiety, R.sub.5 is absent or O, wherein R3 and R4 cannot be the same, for use in the manufacture of a binding moiety-toxin conjugate for the treatment of a solid tumor, and a respective binding moiety-toxin conjugate for the treatment of a solid tumor.

The invention relates to novel methods for synthesizing amanitin derivatives having a hydroxy group attached to the central tryptophan moiety. The invention furthermore relates to novel amanitin derivatives having a hydroxy group attached to position 4, 5 or 7 of the central tryptophan moiety, novel conjugates of such amanitin derivatives, and pharmaceutical compositions comprising such conjugates.

Disclosed is a non-natural amatoxin-type antibody conjugate, said conjugate similar to the natural amatoxin is linked to a biopharmaceutically acceptable salt with a target biomolecule so as to obtain stability in blood plasma, and efficiently kill tumor cells in cells.

The invention provides compositions and methods useful for the depletion of CD117+ cells and for the treatment of various hematopoietic diseases, metabolic disorders, cancers, e.g., acute myeloid leukemia (AML) and autoimmune diseases, among others. Described herein are antibodies, antigen-binding fragments, and conjugates thereof that can be applied to effect the treatment of these conditions, for instance, by depleting a population of CD117+ cells in a patient, such as a human. The compositions and methods described herein can be used to treat a disorder directly, for instance, by depleting a population of CD117+ cancer cells or autoimmune cells. The compositions and methods described herein can also be used to prepare a patient for hematopoietic stem cell transplant therapy and to improve the engraftment of hematopoietic stem cell transplants by selectively depleting endogenous hematopoietic stem cells prior to the transplant procedure.