Provided is a complex composition, of which positional isomers are minimized by using a N-terminus of an immunoglobulin Fc region as a binding site when the immunoglobulin Fc region is used as a carrier. Also provided are a protein complex which is prepared by N-terminal-specific binding of immunoglobulin Fc region, thereby prolonging blood half-life of the physiologically active polypeptide, maintaining in vivo potency at a high level, and having no risk of immune responses, a preparation method thereof, and a pharmaceutical composition including the same for improving in vivo duration and stability of the physiologically active polypeptide. The protein complex may be usefully applied to the development of long-acting formulations of various physiologically active polypeptide drugs.

Provided is a complex composition, of which positional isomers are minimized by using a N-terminus of an immunoglobulin Fc region as a binding site when the immunoglobulin Fc region is used as a carrier. Also provided are a protein complex which is prepared by N-terminal-specific binding of immunoglobulin Fc region, thereby prolonging blood half-life of the physiologically active polypeptide, maintaining in vivo potency at a high level, and having no risk of immune responses, a preparation method thereof, and a pharmaceutical composition including the same for improving in vivo duration and stability of the physiologically active polypeptide. The protein complex prepared by the present invention may be usefully applied to the development of long-acting formulations of various physiologically active polypeptide drugs.

The application relates to a fusion protein comprising an antibody molecule, or antigen-binding fragment thereof, and a member of the vascular endothelial growth factor family, such as VEGF-C or VEGF-D. The antibody molecule preferably binds an antigen associated with angiogenesis, such as the ED-A isoform of fibronectin. In particular, the application relates to the therapeutic use of such fusion protein in the treatment of an inflammatory disease or disorder.

The present disclosure provides compositions and methods for making and using therapeutic agents comprising myeloid cell specific engagers, used for immunotherapy of cancer or infection.

Provided herein are fusion proteins that bind human CD8α, human CD8β, or human PD1 and comprise a mutant IL-2 polypeptide, as well as polynucleotides, host cells, compositions, and methods of use thereof.

The present disclosure provides antibody-drug conjugate structures, which include a cleavable linker that links the antibody to the drug and has a first enzymatically cleavable moiety and a second enzymatically cleavable moiety which includes a glycoside selected from a galactoside, a glucoside, a mannoside, a fucoside, O-GlcNAc, and O-GalNAc. The disclosure also encompasses compounds and methods for production of such conjugates, as well as methods of using the conjugates.

The present invention generally relates to antigen-specific immunoconjugates for selectively delivering effector moieties that influence cellular activity. More specifically, the invention provides novel immunoconjugates comprising a first antigen binding moiety, an Fc domain and a single effector moiety. In addition, the present invention relates to polynucleotides encoding such immunoconjugates, and vectors and host cells comprising such polynucleotides. The invention further relates to methods for producing the immunoconjugates of the invention, and to methods of using these immunoconjugates in the treatment of disease.

Provided are molecular constructs that target tumor necrosis factor receptor 1 (TNFR1) and/or tumor necrosis factor receptor 2 (TNFR2). The constructs are for treating diseases, disorders, and conditions in which these receptors and/or TNF are involved in the etiology or in which their inhibition or activation thereof can ameliorate the disease, disorder, and condition or a symptom thereof. Among the constructs provided herein, are TNFR1 antagonist constructs that are engineered to inhibit TNFR1 function, and to eliminate any TNFR1 agonist activity. The constructs provided herein include agonists and antagonists of TNFR1 and TNFR2 Included also are agonists and antagonists of TNFR2. Agonists of TNFR2 increase regulatory T-cell function to control acute or chronic inflammation. Antagonists of TNFR2 decrease regulatory T-cell function thus increasing immunity, and are for treating cancer and certain immunodeficiency diseases. Methods of treatment of the various diseases in which TNF and its receptors play a role also are provided. Also provided are growth factor ligand trap constructs, and methods of use thereof for treatment of diseases, disorders, and conditions, including cancer.

The present invention generally relates to immunoconjugates, particularly immunoconjugates comprising a mutant interleukin-2 polypeptide and an antibody that binds to PD-1. In addition, the invention relates to polynucleotide molecules encoding the immunoconjugates, and vectors and host cells comprising such polynucleotide molecules. The invention further relates to methods for producing the mutant immunoconjugates, pharmaceutical compositions comprising the same, and uses thereof.

The present invention relates to an immunocytokine comprising (a) a conjugate, and (b) an immunomodulatory antibody or a fragment thereof directly or indirectly linked by covalence to said conjugate, wherein said conjugate comprises (i) a polypeptide comprising the amino acid sequence of the interleukin 15 or derivatives thereof, and a polypeptide comprising the amino acid sequence of the sushi domain of the IL-15Rα or derivatives thereof; and uses thereof.