The invention provides a recombinant Thraustochytriaceae cell for the production of a glycomolecule. The cell comprises a nucleic acid encoding a heterologous glycomolecule, and a sequence encoding a heterologous oligosaccharyltransferase. The cell produces the heterologous glycomolecule having a higher glycan occupancy compared to the same heterologous glycomolecule produced by a corresponding cell not comprising the heterologous oligosaccharyltransferase. The glycan occupancy can be more than 25%. The cells advantageously produce and, optionally secrete, the heterologous glycomolecule. Thus, the invention provides recombinant organisms that provide glycomolecules having a glycosylation profile that is more similar to the glycosylation profile produced in a manunalian cell.

The present invention relates to novel insulin analogues and derivatives thereof, such as acylated insulin analogues, and their pharmaceutical use, in particular in the treatment or prevention of medical conditions relating to diabetes, obesity and cardiovascular diseases.

The present invention relates to novel insulin analogues and derivatives thereof, such as acylated insulin analogues, and their pharmaceutical use, in particular in the treatment or prevention of medical conditions relating to diabetes, obesity and cardiovascular diseases.

Compositions and methods are described for the delivery of a fully human post-translationally modified (HuPTM) therapeutic VEGF-Trap (VEGF-Trap.sup.HuPTM)to a human subject diagnosed with an ocular disease or condition or cancer associated with neovascularization and indicated for treatment with the therapeutic mAb. Delivery may be advantageously accomplished via gene therapye.g., by administering a viral vector or other DNA expression construct encoding the VEGF-Trap.sup.HuPTM to a patient (human subject) diagnosed with an ocular condition or cancer indicated for treatment with the VEGF-Trapto create a permanent depot in a tissue or organ of the patient that continuously supplies the VEGF-Trap.sup.HuPTM, i.e., a human-glycosylated transgene product. Alternatively, the VEGF-Trap.sup.HuPTM, for example, produced in cultured human cell culture, can be administered to the patient for treatment of the ocular disease or cancer.

The present disclosure relates to pharmaceutical compositions comprising a non-naturally occurring fusion molecule and one or more pharmaceutically acceptable carriers, formulated for oral delivery to a subject, and designed to provide for improved, effective therapies for treatment of, e.g., inflammatory diseases, autoimmune diseases, cancer, metabolic disorders, and growth deficiency disorders. The present disclosure relates to a non-toxic mutant form of the Vibrio cholera Cholix gene (ntCholix), a variant of Cholix truncated at amino acid A.sup.386 (Cholix.sup.386) and the use of other various Cholix-derived polypeptide sequences to enhance intestinal delivery of biologically-active therapeutics. The systems and methods described herein provide for: the ability to deliver macromolecule doses without injections; the ability to deliver cargo such as siRNA or antisense molecules into intracellular compartments where their activity is required; and the delivery of nanoparticles and dendrimer-based carriers across biological membranes.

The present disclosure provides for proprotein and activatable proprotein compositions. A proprotein contains a functional protein (i.e. a full length protein or functional fragment thereof) which is coupled to a peptide mask that inhibits the binding of the functional protein to its target or binding partner. An activatable proprotein contains a functional protein coupled to a peptide mask, and further coupled to an activatable linker, wherein in an non-activated state, the peptide mask inhibits binding of the functional protein to its target or binding partner and in an activated state the peptide mask does not inhibit binding of the functional protein to its target or binding partner. Proproteins can provide for reduced toxicity and adverse side effects that could otherwise result from binding of a functional protein at non-treatment sites if it were not inhibited from binding its binding partner. Proproteins can further provide improved biodistribution characteristics. Proproteins containing a peptide mask can display a longer in vivo or serum half-life than the corresponding functional protein not containing a peptide mask. The disclosure further provides methods of screening for, making, and using these proproteins.

The present disclosure relates to pharmaceutical compositions comprising a non-naturally occurring fusion molecule and one or more pharmaceutically acceptable carriers, formulated for oral delivery to a subject, and designed to provide for improved, effective therapies for treatment of, e.g., inflammatory diseases, autoimmune diseases, cancer, metabolic disorders, and growth deficiency disorders.

The present disclosure relates to pharmaceutical compositions comprising a non-naturally occurring fusion molecule and one or more pharmaceutically acceptable carriers, formulated for oral delivery to a subject, and designed to provide for improved, effective therapies for treatment of, e.g., inflammatory diseases, autoimmune diseases, cancer, metabolic disorders, and growth deficiency disorders.

The invention discloses chimeric endocytic receptor CER-based constructs for activating and regulating immune response, and method for using the same. The CER-based constructs are based on the structure of FcRI/ chain and incorporate high-affinity binding domain from receptors or antibodies shown to uptake specific antigen and present the antigen to T cells or B cells to initiate the antigen-specific immune response, Such design has the ability to transform native monocytes or T cells to CER-expressing monocytes (CER-M) or CER-expressing T cells (CER-T) in recognizing and uptake the target antigen and activate subsequent immune responses. Such engineered CER-M or CER-T can be used to treat tumor, viral diseases and autoimmune diseases directly. The endocytosis process with involvement of FcR- may enhance and coordinate T cell activation in combination with T cell activation by other types of constructs such as CAR.

Disclosed is a polypeptide containing an extracellular domain of a synaptogenic protein, and a method for manufacturing a nerve cell, a complex containing a biotin tagged at the C-terminus of the polypeptide, an artificial synapse inducer for coupling the composite to a streptavidin (SAV)-coated substrate and a nerve cell. The complex tagged with a biotin at the C-terminus of the polypeptide containing the extracellular domain of the synaptogenic protein, such as neuroligin-1, can display activity by being attached to the SAV-coated substrate to adjust the orientation thereof without help of a supported lipid bilayer. The complex containing an additional RFP between the extracellular domain and the biotin of the synaptogenic protein not only facilitates easier mass-production, quantification, and tracking, but also displays activity of a normal synaptogenic protein, thereby inducing excitatory or inhibitory synaptic differentiation by being fixed to the substrate and added to the nerve cell culture.