Abstract: The present disclosure provides delivery constructs comprising a carrier coupled to a heterologous payload, wherein coupling of the carrier to the payload can result in transportation of the payload (e.g., a therapeutic payload) into and/or across intact polarized epithelial cells (e.g., epithelial cells of the gut of a mammal). The delivery construct can be part of a pharmaceutical composition that can be orally administered to a subject to provide for improved, effective therapies for treatment of, e.g., inflammatory diseases or autoimmune diseases.

Abstract: The present disclosure provides non-naturally occurring fusion molecules comprising therapeutic cargo moieties, such as IL-22 with a carrier. The disclosure also provides methods and compositions for the production, purification, refolding, formulation, and administration of fusion molecules. Methods and for using the purified molecules to treat and prevent diseases or disorders are also provided herein.

Abstract: An anchored dilator includes a push tube having proximal and distal push tube portions. A dilator tip is coupled with the distal push tube portion and is configured for selectable coupling with a catheter. The dilator tip includes an anchor cuff having a cuff interface. The anchor cuff is configured to transition between a shuttle configuration having a shuttle profile and an anchored configuration having an anchored profile larger than the shuttle profile. A cuff operator assembly is configured to transition the anchor cuff between the anchored and shuttle configurations. The cuff operator assembly includes a cuff operator movably coupled with the dilator tip, and an operator shaft coupled with the cuff operator. The operator shaft extends toward the proximal push tube portion. Actuation of the cuff operator with the operator shaft transitions the anchor cuff between the shuttle configuration and the anchored configuration.

Abstract: The present disclosure provides delivery constructs comprising a carrier coupled to a heterologous payload, wherein coupling of the carrier to the payload can result in transportation of the payload (e.g., a therapeutic payload) into and/or across intact polarized epithelial cells (e.g., epithelial cells of the gut of a mammal). The delivery construct can be part of a pharmaceutical composition that can be orally administered to a subject to provide for improved, effective therapies for treatment of, e.g., inflammatory diseases or autoimmune diseases.

Abstract: Aspects herein relate to a low-friction septum for providing a leak-resistant seal for use in a vascular access device. In an embodiment, a device for vascular access hemostasis is included having an enclosure defining a cavity and configured to at least partially receive a medical device. The device can include a first seal portion and a second seal portion, the cavity disposed between the first seal portion and the second seal portion. The device can include a barrel in structural communication with the second seal portion, the second seal portion including a septum seal. The second seal portion can define two or more discrete portions, each separated by one or more split lines. The discrete portions can include a mating surface to interface with mating surfaces of other discrete portions. The mating surface can include a surface topology including raised portions and depressions. Other embodiments are also included herein.

Abstract: The present disclosure provides delivery constructs comprising a carrier coupled to a heterologous payload, wherein coupling of the carrier to the payload can result in transportation of the payload (e.g., a therapeutic payload) into and/or across intact polarized epithelial cells (e.g., epithelial cells of the gut of a mammal). The delivery construct can be part of a pharmaceutical composition that can be orally administered to a subject to provide for improved, effective therapies for treatment of, e.g., inflammatory diseases or autoimmune diseases.

Abstract: Described herein are cholix-IL-10 fusion proteins, and methods of use thereof, which can be characterized by a distinct response in an individual when administered. This distinct response can comprise changes in levels of one or more markers in the individual and/or co-localization of IL-10 in the Lamina propria of the individual. Further described herein, in some embodiments, are oral formulations of the cholix-IL-10 fusion proteins. Described herein are methods for the purification of an IL-10 delivery construct, including methods for refolding and enrichment, which can result in maintenance of a high percentage of the IL-10 delivery constructs in the biologically active dimer form. Described herein are oral formulations configured for site-specific release of a therapeutic protein in the small intestines or colon. In some cases, the therapeutic protein is in the form of a dimer, such as an IL-10 delivery construct capable of crossing the gut epithelium.

Abstract: The present disclosure provides delivery constructs comprising a carrier coupled to a heterologous payload, wherein coupling of the carrier to the payload can result in transportation of the payload (e.g., a therapeutic payload) into and/or across intact polarized epithelial cells (e.g., epithelial cells of the gut of a mammal). The delivery construct can be part of a pharmaceutical composition that can be orally administered to a subject to provide for improved, effective therapies for treatment of, e.g., inflammatory diseases or autoimmune diseases.

Abstract: Described herein are cholix-IL-10 fusion proteins, and methods of use thereof, which can be characterized by a distinct response in an individual when administered. This distinct response can comprise changes in levels of one or more markers in the individual and/or co-localization of IL-10 in the Lamina propria of the individual. Further described herein, in some embodiments, are oral formulations of the cholix-IL-10 fusion proteins. Described herein are methods for the purification of an IL-10 delivery construct, including methods for refolding and enrichment, which can result in maintenance of a high percentage of the IL-10 delivery constructs in the biologically active dimer form. Described herein are oral formulations configured for site-specific release of a therapeutic protein in the small intestines or colon. In some cases, the therapeutic protein is in the form of a dimer, such as an IL-10 delivery construct capable of crossing the gut epithelium.

Abstract: Described herein are cholix-IL-10 fusion proteins, and methods of use thereof, which can be characterized by a distinct response in an individual when administered. This distinct response can comprise changes in levels of one or more markers in the individual and/or co-localization of IL-10 in the Lamina propria of the individual. Further described herein, in some embodiments, are oral formulations of the cholix-IL-10 fusion proteins. Described herein are methods for the purification of an IL-10 delivery construct, including methods for refolding and enrichment, which can result in maintenance of a high percentage of the IL-10 delivery constructs in the biologically active dimer form. Described herein are oral formulations configured for site-specific release of a therapeutic protein in the small intestines or colon. In some cases, the therapeutic protein is in the form of a dimer, such as an IL-10 delivery construct capable of crossing the gut epithelium.

Abstract: The present disclosure provides non-naturally occurring fusion molecules comprising therapeutic cargo moieties, such as IL-22 with a carrier. The disclosure also provides methods and compositions for the production, purification, refolding, formulation, and administration of fusion molecules. Methods and for using the purified molecules to treat and prevent diseases or disorders are also provided herein.

Abstract: An anchored dilator includes a push tube having proximal and distal push tube portions. A dilator tip is coupled with the distal push tube portion and is configured for selectable coupling with a catheter. The dilator tip includes an anchor cuff having a cuff interface. The anchor cuff is configured to transition between a shuttle configuration having a shuttle profile and an anchored configuration having an anchored profile larger than the shuttle profile. A cuff operator assembly is configured to transition the anchor cuff between the anchored and shuttle configurations. The cuff operator assembly includes a cuff operator movably coupled with the dilator tip, and an operator shaft coupled with the cuff operator. The operator shaft extends toward the proximal push tube portion. Actuation of the cuff operator with the operator shaft transitions the anchor cuff between the shuttle configuration and the anchored configuration.

Abstract: Described herein are cholix-IL-10 fusion proteins, and methods of use thereof, which can be characterized by a distinct response in an individual when administered. This distinct response can comprise changes in levels of one or more markers in the individual and/or co-localization of IL-10 in the Lamina propria of the individual. Further described herein, in some embodiments, are oral formulations of the cholix-IL-10 fusion proteins. Described herein are methods for the purification of an IL-10 delivery construct, including methods for refolding and enrichment, which can result in maintenance of a high percentage of the IL-10 delivery constructs in the biologically active dimer form. Described herein are oral formulations configured for site-specific release of a therapeutic protein in the small intestines or colon. In some cases, the therapeutic protein is in the form of a dimer, such as an IL-10 delivery construct capable of crossing the gut epithelium.

Abstract: The present disclosure provides non-naturally occurring fusion molecules comprising therapeutic cargo moieties, such as IL-22 with a carrier. The disclosure also provides methods and compositions for the production, purification, refolding, formulation, and administration of fusion molecules. Methods and for using the purified molecules to treat and prevent diseases or disorders are also provided herein.

Abstract: The present disclosure provides delivery constructs comprising a carrier coupled to a heterologous payload, wherein coupling of the carrier to the payload can result in transportation of the payload (e.g., a therapeutic payload) into and/or across intact polarized epithelial cells (e.g., epithelial cells of the gut of a mammal). The delivery construct can be part of a pharmaceutical composition that can be orally administered to a subject to provide for improved, effective therapies for treatment of, e.g., inflammatory diseases or autoimmune diseases.

Abstract: Aspects herein relate to a low-friction septum for providing a leak-resistant seal for use in a vascular access device. In an embodiment, a device for vascular access hemostasis is included having an enclosure defining a cavity and configured to at least partially receive a medical device. The device can include a first seal portion and a second seal portion, the cavity disposed between the first seal portion and the second seal portion. The device can include a barrel in structural communication with the second seal portion, the second seal portion including a septum seal. The second seal portion can define two or more discrete portions, each separated by one or more split lines. The discrete portions can include a mating surface to interface with mating surfaces of other discrete portions. The mating surface can include a surface topology including raised portions and depressions. Other embodiments are also included herein.

Abstract: The present disclosure provides non-naturally occurring fusion molecules comprising therapeutic cargo moieties, such as IL-22 with a carrier. The disclosure also provides methods and compositions for the production, purification, refolding, formulation, and administration of fusion molecules. Methods and for using the purified molecules to treat and prevent diseases or disorders are also provided herein.

Abstract: Aspects herein relate to a low-friction septum for providing a leak-resistant seal for use in a vascular access device. In an embodiment, a device for vascular access hemostasis is included having an enclosure defining a cavity and configured to at least partially receive a medical device. The device can include a first seal portion and a second seal portion, the cavity disposed between the first seal portion and the second seal portion. The device can include a barrel in structural communication with the second seal portion, the second seal portion including a septum seal. The second seal portion can define two or more discrete portions, each separated by one or more split lines. The discrete portions can include a mating surface to interface with mating surfaces of other discrete portions. The mating surface can include a surface topology including raised portions and depressions. Other embodiments are also included herein.

Abstract: The invention provides for methods and processes for producing, isolating, and purifying modified proteins. In particular, the invention provides for the production, isolation and purification of PEGylated recombinant methionyl human granulocyte colony stimulating factor used for therapeutic purposes.

Abstract: The present disclosure provides non-naturally occurring fusion molecules comprising therapeutic cargo moieties, such as IL-22 with a carrier. The disclosure also provides methods and compositions for the production, purification, refolding, formulation, and administration of fusion molecules. Methods and for using the purified molecules to treat and prevent diseases or disorders are also provided herein.