The present application provides nerve growth factor (NGF) variants with improved in vivo stability, methods for producing and purifying NGF variants, as well as potential therapeutic applications.

According to some embodiments, a carrier for reducing a likelihood of a pathogen binding to cell structures of a host comprises a core, surface features extending from an exterior surface of the core, wherein the surface features are configured to bind to target areas of cell structures of the host to at least partially block the pathogen from binding to said target areas as a result of competitive inhibition, and a plurality of binding sites along the exterior surface, wherein the binding sites are configured to attract at least one portion of the pathogen, wherein the binding sites are recognizable by the pathogen and are able to be bound by the pathogen, thereby at least partially immobilizing the pathogen and reducing the likelihood of the pathogen binding to target areas of cell structures of the host.

According to some embodiments, a carrier for reducing a likelihood of a pathogen binding to cell structures of a host comprises a core, surface features extending from an exterior surface of the core, wherein the surface features are configured to bind to target areas of cell structures of the host to at least partially block the pathogen from binding to said target areas as a result of competitive inhibition, and a plurality of binding sites along the exterior surface, wherein the binding sites are configured to attract at least one portion of the pathogen, wherein the binding sites are recognizable by the pathogen and are able to be bound by the pathogen, thereby at least partially immobilizing the pathogen and reducing the likelihood of the pathogen binding to target areas of cell structures of the host.

Methods of treating subjects having diseases, disorders, or conditions, including disorders associated with cholesterol homeostasis, responsive to agents modulating Kupffer cell function, including methods of administration and dosing regimens associated therewith, are provided. Methods of treating subjects having liver diseases, disorders, or conditions, including non-alcoholic steatohepatitis and non-alcoholic fatty liver disease, with an IL-10 agent are also provided.

Methods of treating subjects having diseases, disorders, or conditions, including disorders associated with cholesterol homeostasis, responsive to agents modulating Kupffer cell function, including methods of administration and dosing regimens associated therewith, are provided. Methods of treating subjects having liver diseases, disorders, or conditions, including non-alcoholic steatohepatitis and non-alcoholic fatty liver disease, with an IL-10 agent are also provided.

The invention relates to a lock-release method to be applied to biomolecules, such as antibodies, to improve the purification, production, stability and storage of biomolecules. A biomolecule is covalently bound to a polymer support comprising a diketone group so that the biomolecule can be purified, produced and/or stored before being released from the support. The diketone group of the polymer support is a 1,3-ketoester, 1,3-ketothioester or 1,3-ketoamide is a group of Formula (1): R.sup.1 is an optionally substituted hydrocarbyl, perhalogenated hydrocarbyl, or a heterocyclyl group; Y is hydrogen, an optionally substituted hydrocarbyl, or a heterocyclyl group; X is —O, —NR.sup.2 or —S, wherein the free valence of —O, —NR.sup.2 or —S is bonded to the support optionally via a linker; and R.sup.2 is hydrogen, an optionally substituted hydrocarbyl, or a heterocyclyl group. The invention also relates to a polymer support comprising the diketone group. ##STR00001##

The invention relates to a lock-release method to be applied to biomolecules, such as antibodies, to improve the purification, production, stability and storage of biomolecules. A biomolecule is covalently bound to a polymer support comprising a diketone group so that the biomolecule can be purified, produced and/or stored before being released from the support. The diketone group of the polymer support is a 1,3-ketoester, 1,3-ketothioester or 1,3-ketoamide is a group of Formula (1): R.sup.1 is an optionally substituted hydrocarbyl, perhalogenated hydrocarbyl, or a heterocyclyl group; Y is hydrogen, an optionally substituted hydrocarbyl, or a heterocyclyl group; X is —O, —NR.sup.2 or —S, wherein the free valence of —O, —NR.sup.2 or —S is bonded to the support optionally via a linker; and R.sup.2 is hydrogen, an optionally substituted hydrocarbyl, or a heterocyclyl group. The invention also relates to a polymer support comprising the diketone group. ##STR00001##

The present invention provides an in vitro method for identifying a compound that promotes endothelial cell adhesion, endothelial cell spreading, endothelial cell migration and/or endothelial cell proliferation for the manufacture of a diagnostic or therapeutic agent. The present invention further provides the identified compounds and pharmaceutical compositions, and assays and kits for identifying a compound or using a compound that promotes endothelial cell adhesion, endothelial cell spreading, endothelial cell migration and/or endothelial cell proliferation and is useful for bioprinting.

The present invention provides an in vitro method for identifying a compound that promotes endothelial cell adhesion, endothelial cell spreading, endothelial cell migration and/or endothelial cell proliferation for the manufacture of a diagnostic or therapeutic agent. The present invention further provides the identified compounds and pharmaceutical compositions, and assays and kits for identifying a compound or using a compound that promotes endothelial cell adhesion, endothelial cell spreading, endothelial cell migration and/or endothelial cell proliferation and is useful for bioprinting.

The present invention provides methods for isolating an active polypeptide or immunoconjugate by purification of a solution containing both the active polypeptide or immunoconjugate and an acidic variant thereof, such as a deamidated variant, using anion exchange chromatography. The present invention also provides compositions, formulations, and unit dosage forms comprising the purified polypeptide or immunoconjugate.