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 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 invention includes compositions and methods for making and using the next generation of activatable pro-cytokine drugs by using a single-chain fragment crystallizable (Fc) region. This single-chain Fc fusion protein is engineered according to the formulas: P1-L-Fc-L-P2-L-Fc, or P1-L-Fc-L-P2-L-Fc-L-P3 in a linear sequence from amino- to carboxy-terminus, wherein protein (P) is the biologically active moiety, e.g., an antibody, or an antigen-binding fragment, or a cytokine receptor, or a cytokine, or a fusion protein consisting of above-mentioned components; L is optional and a protease cleavable, or non-cleavable linker (up to 50-mers amino acids) that is processed by enzymes enriched in tumor tissues, wherein P1, P2, and P3 are different biologically active moieties, but at least one of them is a cytokine that forms an intramolecular heterodimer. Processing the cleavable linker by tumor-specific enzymes serves as a switch to activate the cytokine in the tumor microenvironment.

The present invention includes compositions and methods for making and using the next generation of activatable pro-cytokine drugs by using a single-chain fragment crystallizable (Fc) region. This single-chain Fc fusion protein is engineered according to the formulas: P1-L-Fc-L-P2-L-Fc, or P1-L-Fc-L-P2-L-Fc-L-P3 in a linear sequence from amino- to carboxy-terminus, wherein protein (P) is the biologically active moiety, e.g., an antibody, or an antigen-binding fragment, or a cytokine receptor, or a cytokine, or a fusion protein consisting of above-mentioned components; L is optional and a protease cleavable, or non-cleavable linker (up to 50-mers amino acids) that is processed by enzymes enriched in tumor tissues, wherein P1, P2, and P3 are different biologically active moieties, but at least one of them is a cytokine that forms an intramolecular heterodimer. Processing the cleavable linker by tumor-specific enzymes serves as a switch to activate the cytokine in the tumor microenvironment.

The present invention relates, in part, to agents, chimeric proteins and protein complexes that bind fibroblast activation protein (FAP) and their use as diagnostic and therapeutic agents. The present invention further relates to pharmaceutical compositions comprising the FAP binding agents, chimeric proteins and protein complexes and their use in the treatment of various diseases.

The present invention relates, in part, to agents, chimeric proteins and protein complexes that bind fibroblast activation protein (FAP) and their use as diagnostic and therapeutic agents. The present invention further relates to pharmaceutical compositions comprising the FAP binding agents, chimeric proteins and protein complexes and their use in the treatment of various diseases.

Described is a method for treating an infectious disease, cancer, or myeloproliferative disease in a subject, wherein a 50 to 540 μg dose of a pegylated type I interferon is administered to the subject at a regular interval for a treatment period, the interval being 3 to 8 weeks.

Described is a method for treating an infectious disease, cancer, or myeloproliferative disease in a subject, wherein a 50 to 540 μg dose of a pegylated type I interferon is administered to the subject at a regular interval for a treatment period, the interval being 3 to 8 weeks.

The present disclosure is directed to compositions comprising modified interferon-α2 polypeptides having interferon-α2 activity and reduced immunogenicity. In aspects, said modified interferon-α2 polypeptides are hyperglycosylated, such as by addition of a GM-CSF-derived peptide sequence with multiple O-glycosylation sites. Furthermore, the present disclosure provides compositions comprising a nucleic acid molecule encoding said modified interferon-α2. The present disclosure also provides compositions comprising a recombinant protein expression cell line comprising said nucleic acid molecule encoding said modified interferon-α2; wherein said recombinant protein expression cell comprises a plasmid or vector containing said nucleic acid molecule. Also disclosed are pharmaceutical compositions comprising a modified interferon-α2 having interferon-α2 activity with reduced immunogenicity, as well as methods of use of said pharmaceutical formulations for treatment of medical conditions in a subject.

The present disclosure is directed to compositions comprising modified interferon-α2 polypeptides having interferon-α2 activity and reduced immunogenicity. In aspects, said modified interferon-α2 polypeptides are hyperglycosylated, such as by addition of a GM-CSF-derived peptide sequence with multiple O-glycosylation sites. Furthermore, the present disclosure provides compositions comprising a nucleic acid molecule encoding said modified interferon-α2. The present disclosure also provides compositions comprising a recombinant protein expression cell line comprising said nucleic acid molecule encoding said modified interferon-α2; wherein said recombinant protein expression cell comprises a plasmid or vector containing said nucleic acid molecule. Also disclosed are pharmaceutical compositions comprising a modified interferon-α2 having interferon-α2 activity with reduced immunogenicity, as well as methods of use of said pharmaceutical formulations for treatment of medical conditions in a subject.