The present invention provides fusion proteins comprising leptin and a second protein. The presence of the second protein provides increased biological activity and/or increased half-life in vivo. The present invention also provides human, canine and feline leptin molecules fused to peptides, antibodies or antibody fragments which enhances the abilities of the leptin molecules to transport through the blood-brain-barrier (BBB). The present invention also provides fusion proteins further comprising a peptide agonist that is capable of binding to and stimulate one, two or all three of the following receptors: GLP-1 receptor, Glucagon receptor, and GIP receptor. Also disclosed is a method of production such fusion proteins through recombinant technologies. The invention further discloses a pharmaceutical composition comprising one of the fusion proteins as an active intergradient as well as a method for using such a pharmaceutical composition to treat diseases in dogs, cats and humans.

VH domain, in which: (i) the amino acid residue at position 112 is one of K or Q; and/or (ii) the amino acid residue at position 89 is T; and/or (iii) the amino acid residue at position 89 is L and the amino acid residue at position 110 is one of K or Q; and (iv) in each of cases (i) to (iii), the amino acid at position 11 is preferably V; and in which said VH domain contains a C-terminal extension (X)n, in which n is 1 to 10, preferably 1 to 5, such as 1, 2, 3, 4 or 5 (and preferably 1 or 2, such as 1); and each X is an (preferably naturally occurring) amino acid residue that is independently chosen, and preferably independently chosen from the group consisting of alanine (A), glycine (G), valine (V), leucine (L) or isoleucine (I).

Provided herein are immunomodulatory proteins comprising ICOSL variants and nucleic acids encoding such proteins. The immunomodulatory proteins provide therapeutic utility for a variety of immunological and oncological conditions. Compositions and methods for making and using such proteins are provided.

The present invention provides therapeutic agents and compositions comprising elastin-like peptides (ELPs) and therapeutic proteins. In some embodiments, the therapeutic protein is a GLP-1 receptor agonist, insulin, or Factor VII/VIIa, including functional analogs. The present invention further provides encoding polynucleotides, as well as methods of making and using the therapeutic agents. The therapeutic agents have improvements in relation to their use as therapeutics, including, inter alia, one or more of half-life, clearance and/or persistance in the body, solubility, and bioavailability.

A pharmaceutical composition for enhancing radiation therapy, containing a fusion protein dimer is disclosed. The fusion protein dimer includes an IL-2 protein and a CD80 protein. A method of radiation therapy for cancer, using the composition is also disclosed. The composition for enhancing radiation therapy may increase the effect of radiation therapy in cancer treatment.

Provided herein are engineered IL2 polypeptides and fusion proteins thereof. Also provided are methods of modulating an immune response by administering an engineered IL2 polypeptide or a fusion protein thereof. The engineered IL2 polypeptides and fusion proteins thereof demonstrate increased binding to IL2Rβ, decreased binding to IL2Rα, or both.

The present invention provides modified von Willebrand Factor molecules, methods for their preparation and uses thereof. The invention further provides pharmaceutical compositions for treating coagulation disorders.

The present invention relates to long-acting insulin analogues having an increased in vivo half-life in which the amino acid at position 22 of the B-chain of native insulin is substituted and one or more amino acids of the A-chain or B-chain of native insulin are additionally substituted, and to long-acting insulin analogue derivatives having a further increased in vivo half-life in which an albumin-binding domain is additionally fused to the long-acting insulin analogues. The insulin analogues or insulin analogue derivatives according to the present invention have a significantly increased in vivo half-life, and thus can provide convenience to diabetic patients who self-administer insulin by injection.

VEGFR-Fc fusion protein formulations and methods of making using such formulations are provided herein. In one embodiment, the formulation is an ophthalmic formulation, such as for intravitreal administration. In some embodiments, the VEGFR-Fc fusion protein is aflibercept.

The present invention includes compositions and methods for treating disease and disorders associated with pathological calcification or pathological ossification.