Abstract: The present application relates to humanized and/or deimmunized antibodies, antibody fragments or antibody derivatives that bind to Prostate Specific Membrane Antigen (PSMA) and methods for using said antibodies, antibody fragments or antibody derivatives in the treatment of prostate cancer and other neoplastic as well as neurological diseases.

Abstract: This application relates to amatoxin analogs in which the trans-4-substituent on the proline residue of the amatoxin is an R group other than a hydroxy, constructs comprising such amatoxin analogs coupled to a linker and conjugates comprising such amatoxin analog-linker constructs conjugated to a target moiety. The application also relates to uses of such amatoxin analogs, for example, in treatment of cancer.

Abstract: The invention relates to a nozzle arrangement (1) for applying fluids (20), in particular thermoplastic materials, to a substrate (21), wherein the nozzle arrangement (1) comprises a base body (14), which can be connected, preferably exchangeably, to a mounting region of a distributor (30), and a front lateral surface.

Abstract: The present invention pertains to treatment regimens to increase the therapeutic index of antibody-drug conjugates in particular antibody-drug conjuagtes comprising amatoxins. The present invention furthermore pertains to amatoxin-based antibody-drug conjuagtes for use in said treatment regimens.

Abstract: The present application relates to humanized and/or deimmunized antibodies, antibody fragments or antibody derivatives that bind to Prostate Specific Membrane Antigen (PSMA) and methods for using said antibodies, antibody fragments or antibody derivatives in the treatment of prostate cancer and other neoplastic as well as neurological diseases.

Abstract: The present invention relates to prodrugs comprising a linker comprising five- or six-membered cyclic acetals and an adjacent specific cleavage site, and to precursor compounds for the synthesis of said prodrugs. In one aspect the present invention relates to antibody-targeted amatoxin conjugates comprising said linkers, to methods for their synthesis, and to the use of said antibody-targeted amatoxin conjugates. In a further aspect, the invention relates to pharmaceutical compositions comprising said conjugates, and to the use of said conjugates or compositions for therapeutic purposes, in particular for tumor therapy and oncology.

Abstract: Amatoxins, as well as antibody-drug conjugates (ADCs) comprising an amatoxin are provided, as well as compositions and methods of using the same. The compositions and methods provided herein can be used for cancer therapy. They 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. Methods and compositions for the treatment of various hematopoietic diseases, metabolic disorders, cancers, and autoimmune diseases, as well as prevention of graft-versus-host-disease (GVHD), are provided.

Abstract: The invention relates to a PSMA-targeting conjugate comprising (a) an amatoxin; (b) a small molecule PSMA-targeting moiety; and (c) optionally a linker linking said amatoxin and said small molecule PSMA-targeting moiety. The invention furthermore relates to a pharmaceutical composition comprising such conjugate.

Abstract: The present application relates to conjugates comprising an amatoxin, a target-binding moiety wherein the target is CD37, i.e., a CD37-binding moiety, and optionally a linker linking said amatoxin and said CD37-binding moiety. The invention further relates to the synthesis of said conjugates. In addition, the invention relates to a pharmaceutical composition comprising such conjugate for use in the treatment of immune cell-, particularly B-cell and/or lymphoma associated diseases and/or malignancies.

Abstract: A method for optimizing energy conversion installation service measures, wherein the energy conversion installation has at least the following machines: at least one gas turbine; at least one generator; and optionally at least one steam turbine; wherein repairs are carried out on the at least one machine, in particular a defective component or defective components of the at least one machine either is/are or will be replaced by a new, identical component or new, identical components and/or repaired; and wherein, while carrying out these repairs, further measures for extending the service life of machines or the components thereof and/or further measures for optimizing machines or the components thereof are carried out.

Abstract: The invention relates to a conjugate comprising (a) an amatoxin comprising (i) an amino acid 4 with a 6?-deoxy position; and (ii) an amino acid 8 with an S-deoxy position; (b) a BCMA-binding moiety comprising (i) the variable domains of humanized antibody J22.9-ISY, and (ii) a heavy chain constant region comprising a D265C mutation; and (c) a protease-cleavable linker linking said amatoxin and said target-binding moiety. The invention furthermore relates to a pharmaceutical composition comprising such conjugate, particularly for use in the treatment of multiple myeloma.

Abstract: The present application relates to a composition comprising (a) at least one immune checkpoint inhibitor and (b) at least one conjugate, wherein said conjugate is comprising (i) a target binding moiety, (ii) at least one amatoxin, and (iii) optionally at least one linker connecting said target binding moiety with said at least one amatoxin. The present application further relates to said composition for use in treating a patient having a cancer, and to a pharmaceutical formulation comprising said composition and additional excipients, as well as to methods of producing and using said composition.

Abstract: A nozzle arrangement for applying fluids to a substrate has a connection body that is connectable to a distributor mounting region and has a spray nozzle that is connectable to the connection body. The spray nozzle has a nozzle body that longitudinally extends and has a first fluid channel for the fluid to be applied to the substrate. The spray nozzle has a nozzle housing in which the nozzle body is received. Second fluid channels for shaping air are formed between a lateral surface and inner of the nozzle body. The second fluid channels extend in the direction of a nozzle outlet opening of the nozzle body such that, by way of the shaping air dispensed from the second fluid channels at the nozzle outlet region, a spiral-shaped deflection of the fluid dispensed from the nozzle outlet opening of the nozzle body is created.

Abstract: The use of different ceramic layers allows different configurations of gas turbines to be produced each of which is optimized for a respective use of base load operation or peak load operation.

Abstract: The present invention relates to an amatoxin-linker construct comprising an amatoxin according to formula (I) wherein: R1 and R2 are each —OH, R3 is NH2, or a linker which carries a reactive group Y for linking said amatoxin to a target-binding moiety, R4 is H or a linker which carries a reactive group Y for linking said amatoxin to a target-binding moiety, R5 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.

Abstract: Amatoxins, as well as antibody-drug conjugates (ADCs) comprising an amatoxin are provided, as well as compositions and methods of using the same. The compositions and methods provided 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. Methods and compositions for the treatment of various hematopoietic diseases, metabolic disorders, cancers, and autoimmune diseases, as well as prevention of graft-versus-host-disease (GVHD), are provided.

Abstract: A nozzle includes a back plate having a first inlet passage and a first discharge opening at one end of the first inlet passage, a front plate and a plurality of nozzle plates secured between the back plate and the front plate. The plurality of nozzle plates includes a first plenum plate, a second plenum plate and a discharge plate. The first plenum plate has a first plenum, the second plenum plate has a second plenum and a second plenum projection extending into the second plenum, and the discharge plate is disposed between the first plenum plate and the second plenum plate and has one or more orifices. The first plenum is disposed in fluid communication with the first inlet passage and is configured to receive a first fluid from the first inlet passage via the first discharge opening. The one or more orifices are disposed in fluid communication with the first plenum and are configured to receive the first fluid from the first plenum.

Abstract: The invention relates to conjugates comprising amatoxins and antibodies, in particular amatoxins linked to antibodies comprising specific cysteine residues.

Abstract: The invention relates to a PSMA-targeting conjugate comprising (a) an amatoxin; (b) a small molecule PSMA-targeting moiety; and (c) optionally a linker linking said amatoxin and said small molecule PSMA-targeting moiety. The invention furthermore relates to a pharmaceutical composition comprising such conjugate.

Abstract: An apparatus for the intermittent application of a liquid to pasty medium onto an application surface, comprising an application valve which can be switched between an open and a closed state and is intended for dispensing the medium onto the application surface, a volumetric delivery pump for metering a volume of the medium to be passed on to the application valve, and a drive for operating the volumetric delivery pump is, inter alia, described and illustrated. The characteristic feature consists in that the apparatus has an electronic controller which, in each case cyclically, activates the drive and the application valve in dependence on each other.