Abstract: The present disclosure provides a D1L2 enzyme lacking a proline-rich domain (PRD) and/or lacking the C-terminal Arg residue, which is efficiently produced in microbial expression systems such as Pichia pastoris, and has high activity for degrading chromatin at acidic pH. The present disclosure provides methods of the production and use of the D1L2 enzyme in therapy.

Abstract: A shaft according to the invention for a flexible endoscope or for a flexible endoscopic instrument includes a first shaft section and a second shaft section arranged on the distal side of the first shaft section, wherein the second shaft section is able to be angled by means of at least one pull element extending inside the second shaft section, wherein the second shaft section has a support structure, and wherein an adapter is arranged between a distal end region of the first shaft section and a proximal end region of the support structure. The invention also relates to a method for assembling a shaft for a flexible endoscope or for a flexible endoscopic instrument, and also to a flexible endoscope and a flexible endoscopic instrument.

Abstract: The present disclosure provides engineered human extracellular DNASE proteins (e.g., variants of DNASE1 (D1), DNASE1-LIKE 1 (D1L1), DNASE1-LIKE 2 (D1L2), DNASE1-LIKE 3 Isoform 1 (D1L3), DNASE1-LIKE 3 Isoform 2 (D1L3-2), DNASE2A (D2A), and DNASE2B (D2B)) that are useful for treating conditions characterized by neutrophil extracellular trap (NET) accumulation and/or release. In accordance with the invention, the DNase variant has advantages for therapy and/or large-scale manufacturing.

Abstract: In consideration of increasing throughput rate of a stable operating process as well as making the process energy-efficient, the aim is to optimise a fluidised bed opposed jet mill and a dedicated process to produce ultrafine particles from a feed material of low bulk density with a housing in vertical design, with a product feed point and a product discharge, with a grinding zone located in the lower area of the housing which has grinding nozzles spaced evenly around the circumference whose jets intersect at one central point and with a classifying device installed in the upper area of the housing. This is achieved by the feed material dosed to the mill from the bottom into the mill sump as a gas-particle mixture, whereby a deflector hood is located above the feed point and below the grinding nozzle level, and the grinding gas nozzles designed to be flush with the walls.

Abstract: Embodiments of the technology described herein are based upon the discoveries that neutrophil extracellular traps (NETs) provide a stimulus for thrombus formation and that NETs are present in stored blood products. Accordingly, some embodiments relate to methods of treating and preventing toxicity of NETs and thrombosis caused by NETs. Additional embodiments are directed towards methods of treating stored blood products to prevent transfusion-related injuries.

Abstract: The present disclosure provides engineered human extracellular DNASE proteins (e.g., variants of DNASE1 (D1), DNASE1-LIKE 1 (D1L1), DNASE1-LIKE 2 (DTL2), DNASE1-LIKE 3 Isoform 1 (DTL3), DNASE1-LIKE 3 Isoform 2 (DTL3-2), DNASE2A (D2A), and DNASE2B (D2B)) that are useful for treating conditions characterized by neutrophil extracellular trap (NET) accumulation and/or release. In accordance with the invention, the DNase variant has advantages for therapy and/or large-scale manufacturing.

Abstract: Embodiments of the technology described herein are based upon the discoveries that neutrophil extracellular traps (NETs) provide a stimulus for thrombus formation and that NETs are present in stored blood products. Accordingly, some embodiments relate to methods of treating and preventing toxicity of NETs and thrombosis caused by NETs. Additional embodiments are directed towards methods of treating stored blood products to prevent transfusion-related injuries.

Abstract: The present invention relates to the treatment of tissue adhesions, e.g. tissue adhesions that occur after surgical interventions. More specifically, the invention refers to an enzyme having DNAse activity for use in a method of treating or preventing tissue adhesions. The invention also relates to a pharmaceutical composition that comprises an enzyme having DNAse activity for use in a method of treating or preventing tissue adhesions.

Abstract: The present disclosure provides a library of engineered DNASE proteins (including DNASE1, DNASE1-LIKE 1, DNASE1-LIKE 2, DNASE1-LIKE 3, DNASE2A, DNASE2B) that allows to select drug candidates for developing therapeutics for treating conditions characterized by neutrophil extracellular trap (NET) accumulation and/or release. In accordance with the invention, the selected DNase variant has improved properties, including properties amenable to clinical development, including manufacturing, toxicology, pharmacokinetic, and/or use in therapy.

Abstract: The present disclosure provides a library of engineered DNASE proteins (including DNASE1, DNASE1-LIKE 1, DNASE1-LIKE 2, DNASE1-LIKE 3, DNASE2A, DNASE2B) that allows to select drug candidates for developing therapeutics for treating conditions characterized by neutrophil extracellular trap (NET) accumulation and/or release. In accordance with the invention, the selected DNase variant has improved properties, including properties amenable to clinical development, including manufacturing, toxicology, pharmacokinetic, and/or use in therapy.

Abstract: The present disclosure provides engineered human extracellular DNASE proteins (e.g., variants of DNASE1 (D1), DNASE1-LIKE 1 (D1L1), DNASE1-LIKE 2 (DTL2), DNASE1-LIKE 3 Isoform 1 (DTL3), DNASE1-LIKE 3 Isoform 2 (DTL3-2), DNASE2A (D2A), and DNASE2B (D2B)) that are useful for treating conditions characterized by neutrophil extracellular trap (NET) accumulation and/or release. In accordance with the invention, the DNase variant has advantages for therapy and/or large-scale manufacturing.

Abstract: The present invention relates to a non-human mammalian animal which has been modified to have in the blood, plasma and/or serum (a) an increased number of leukocytes and/or neutrophils, and (b) a reduced activity of the DNase 1 and/or DNase 1-like 3 enzymes. The non-human mammalian animal is particularly suitable for studying inflammation and/or a disease associated with inflammation. In a further aspect, the invention relates to the use of the non-human mammalian animal as a model for identifying therapeutic or diagnostic targets of inflammation and/or a disease associated with inflammation. In a still further aspect, the invention relates the use of the non-human mammalian animal as a model for drug candidate testing. In addition, a method for testing an anti-inflammatory drug candidate against extracellular DNA is provided. Finally, a method for testing an anti-inflammatory drug candidate for modifying the formation or degradation of neutrophil extracellular traps is provided.

Abstract: In consideration of increasing throughput rate of a stable operating process as well as making the process energy-efficient, the aim is to optimise a fluidised bed opposed jet mill and a dedicated process to produce ultrafine particles from a feed material of low bulk density with a housing in vertical design, with a product feed point and a product discharge, with a grinding zone located in the lower area of the housing which has grinding nozzles spaced evenly around the circumference whose jets intersect at one central point and with a classifying device installed in the upper area of the housing. This is achieved by the feed material dosed to the mill from the bottom into the mill sump as a gas-particle mixture, whereby a deflector hood is located above the feed point and below the grinding nozzle level, and the grinding gas nozzles designed to be flush with the walls.

Abstract: The present disclosure provides a library of engineered DNASE proteins (including DNASE1, DNASE1-LIKE 1, DNASE1-LIKE 2, DNASE1-LIKE 3, DNASE2A, DNASE2B) that allows to select drug candidates for developing therapeutics for treating conditions characterized by neutrophil extracellular trap (NET) accumulation and/or release. In accordance with the invention, the selected DNase variant has improved properties, including properties amenable to clinical development, including manufacturing, toxicology, pharmacokinetic, and/or use in therapy.

Abstract: The present disclosure provides a library of engineered DNASE proteins (including DNASE1, DNASE1-LIKE 1, DNASE1-LIKE 2, DNASE1-LIKE 3, DNASE2A, DNASE2B) that allows to select drug candidates for developing therapeutics for treating conditions characterized by neutrophil extracellular trap (NET) accumulation and/or release. In accordance with the invention, the selected DNase variant has improved properties, including properties amenable to clinical development, including manufacturing, toxicology, pharmacokinetic, and/or use in therapy.

Abstract: The present disclosure provides D1L3 enzymes having complete or partial C-terminal deletions of the basic domain (BD), which have substantially enhanced chromatin-degrading activity. In various aspects, the invention provides chromatinase enzyme therapy, which is optionally provided by delivering polynucleotides encoding chromatinases such as D1L3, or by delivering host cells expressing and secreting the same.

Abstract: The present invention provides engineered DNase proteins (including DNase1-like 3 and DNase1) that are useful for treating conditions characterized by neutrophil extracellular trap (NET) accumulation and/or release. In some aspects, the invention provides compositions and methods for preventing or treating vascular occlusion involving NETs. As demonstrated herein, NETs participate in a non-canonical mechanism for vascular occlusion, which is not dependent on fibrin or platelets.

Abstract: The present disclosure provides D1L3 enzymes having complete or partial C-terminal deletions of the basic domain (BD), which have substantially enhanced chromatin-degrading activity. In various aspects, the invention provides chromatinase enzyme therapy, which is optionally provided by delivering polynucleotides encoding chromatinases such as D1L3, or by delivering host cells expressing and secreting the same.

Abstract: The present disclosure provides engineered human extracellular DNASE proteins (e.g., variants of DNASE1 (D1), DNASE1-LIKE 1 (D1L1), DNASE1-LIKE 2 (D1L2), DNASE1-LIKE 3 Isoform 1 (D1L3), DNASE1-LIKE 3 Isoform 2 (D1L3-2), DNASE2A (D2A), and DNASE2B (D2B)) that are useful for treating conditions characterized by neutrophil extracellular trap (NET) accumulation and/or release. In accordance with the invention, the DNase variant has advantages for therapy and/or large-scale manufacturing.

Abstract: The present invention provides engineered DNase proteins (including DNase1-like 3 and DNase1) that are useful for treating conditions characterized by neutrophil extracellular trap (NET) accumulation and/or release. In some aspects, the invention provides compositions and methods for preventing or treating vascular occlusion involving NETs. As demonstrated herein, NETs participate in a non-canonical mechanism for vascular occlusion, which is not dependent on fibrin or platelets.