Aspects of the application provide anti-hemojuvelin antibodies and methods of using the same in treating anemias of chronic disease, iron-restricted anemias, and/or conditions associated with anemia.

The instant disclosure provides antibodies that specifically bind to human PD-1 and antagonize PD-1 function. Also provided are pharmaceutical compositions comprising these antibodies, nucleic acids encoding these antibodies, expression vectors and host cells for making these antibodies, and methods of treating a subject using these antibodies.

Herein is reported a heterodimeric polypeptide comprising a first polypeptide comprising in N-terminal to C-terminal direction at least a portion of an immunoglobulin hinge region, which comprises one or more cysteine residues, an immunoglobulin CH2-domain and an immunoglobulin CH3-domain, and a second polypeptide comprising in N-terminal to C-terminal direction at least a portion of an immunoglobulin hinge region, which comprises one or more cysteine residues, an immunoglobulin CH2-domain and an immunoglobulin CH3-domain, wherein the first polypeptide comprises the mutations Y349C, T366S, L368A and Y407V (hole-chain) and the second polypeptide comprises the mutations S354C and T366W (knob-chain), and wherein the first polypeptide (hole-chain) comprises the mutations i) I253A or I253G, and ii) L314A or L314G or L314D, and wherein the first polypeptide and the second polypeptide are connected by one or more disulfide bridges, and wherein the CH3-domain of the first polypeptide and the CH3-domain of the second polypeptide both bind or both do not bind to protein A (numbering according to the Kabat EU index).

Herein is reported an IgG class Fc-region comprising a first variant Fc-region polypeptide and a second variant Fc-region polypeptide, wherein a) the first variant Fc-region polypeptide is derived from a first parent IgG class Fc-region polypeptide and the second variant Fc-region polypeptide is derived from a second parent IgG class Fc-region polypeptide, whereby the first parent IgG class Fc-region polypeptide is identical to or different from the second parent IgG class Fc-region polypeptide, and b) the first variant Fc-region polypeptide differs from the second variant Fc-region polypeptide in one or more amino acid residues other than those amino acid residues in which the first parent IgG class Fc-region polypeptide differs from the second parent IgG class Fc-region polypeptide, and c) the IgG class Fc-region comprising the first variant Fc-region polypeptide and the second variant Fc-region polypeptide has an affinity to a human Fc-receptor that is different than that of an IgG class Fc-region comprising the first parent IgG class Fc-region polypeptide of a) and the second parent IgG class Fc-region polypeptide of a), wherein either the first Fc-region polypeptide or the second Fc-region polypeptide or both Fc-region polypeptides comprise independently of each other one of the following mutations or combination of mutations: T307H, or Q311H, or E430 H, or N434H, or T307H and Q311H, or T307H and E430H, or T307H and N434A, or T307H and N434H, or T307Q and Q311H, or T307Q and E430H, or T307Q and N434H, or T307H and Q311H and E430H and N434A, or T307H and Q311H and E430H and N434H, or T307H and Q311H and E430H and N434Y, or T307Q and Q311H and E430H and N434A, or T307Q and Q311H and E430H and N434H, or T307Q and Q311H and E430H and N434Y, or T307Q and V308P and N434Y and Y436H, or T307H and M252Y and S254T and T256E, or T307Q and M252Y and S254T and T256E, or Q311H and M252Y and S254T and T256E, or E430 H and M252Y and S254T and T256E, or N434H and M252Y and S254T and T256E, or T307H and Q311H and M252Y and S254T and T256E, or T307H and E430H and M252Y and S254T and T256E, or T307H and N434A and M252Y and S254T and T256E, or T307H and N434H and M252Y and S254T and T256E, or T307Q and Q311H and M252Y and S254T and T256E, or T307Q and E430H and M252Y and S254T and T256E, or T307Q and N434H and M252Y and S254T and T256E, or T307H and Q311H and E430H and N434A and M252Y and S254T and T256E, or T307H and Q311H and E430H and N434H and M252Y and S254T and T256E, or T307H and Q311H and E430H and N434Y and M252Y and S254T and T256E, or T307Q and Q311H and E430H and N434A and M252Y and S254T and T256E, or T307Q and Q311H and E430H and N434H and M252Y and S254T an

The present disclosure relates to antibody molecules that bind specifically to C-MET and related nucleic acid molecules, vectors and host cells. Also provided are medical uses of such antibody molecules. The claimed anti C-Met antibodies of the present application have been selected by in silico engineering. Some of the antibodies have been generated and further characterized after expression in mammalian expression system.

An objective of the present invention is to provide a polypeptide containing an Fc region having maintained or decreased binding activities towards both allotypes of FcγRIIa, types H and R, and having enhanced FcγRIIb-binding activity in comparison with a parent polypeptide; a pharmaceutical composition containing the polypeptide; an agent for treating or preventing immunological inflammatory diseases that includes the pharmaceutical composition; a production method thereof; and a method for maintaining or decreasing binding activities towards both allotypes of FcγRIIa and enhancing the FcγRIIb-binding activity. Specifically, it is found that a polypeptide containing an antibody Fc region that has an alteration of substituting Pro at position 238 (EU numbering) with Asp or Leu at position 328 (EU numbering) with Glu enhances FcγRIIb-binding activity, and maintains or decreases binding activities towards both allotypes of FcγRIIa, types H and R. It is also found that a polypeptide containing an antibody Fc region that contains an alteration of substituting Pro at position 238 (EU numbering) with Asp and several other alterations, enhances FcγRIIb-binding activity, and maintains or decreases binding activities towards both allotypes of FcγRIIa, types H and R.

An scFv-Fc dimer binds and neutralizes TGFβ1 selectively and with high affinity and avidity. The scFv region may comprise the same VH and VL domains or CDR regions as metelimumab. The unique combination of their smaller size, high selectivity, potency against TGFβ1, and long in vivo half-life makes the scFv-Fc dimers ideal candidates for therapeutic applications.

Aspects of the application provide anti-hemojuvelin antibodies and methods of using the same in treating myelofibrosis and/or conditions associated with myelofibrosis.

Disclosed are antibodies binding to human IL-4R, having identical variable regions and different constant regions, wherein the variable regions can specifically bind to human IL-4R, and the constant regions affect the activity of the whole antibody through an amino acid site mutation. The above-mentioned antibodies can be used to treat diseases related to IL-4R overexpression, such as atopic dermatitis, asthma, etc., and thus possesses good clinical application prospects.

The present invention relates to compositions and methods for antibody-mediated therapy. In particular, provided herein are engineered immunoglobulins with altered half-life.