12 results about "Hinge region" patented technology

This specification provides a bispecific agonist antibody having a modified hinge region, and a method for using the same.

The present inventors succeeded in improving the antibody constant region to have increased stability under acid conditions, reduced heterogeneity originated from disulfide bonds in the hinge region, reduced heterogeneity originated from the H chain C terminus, and increased stability at high concentrations as well as in discovering novel constant region sequences having reduced Fcγ receptor-binding, while minimizing the generation of novel T-cell epitope peptides. As a result, the present inventors successfully discovered antibody constant regions with improved physicochemical properties (stability and homogeneity), immunogenicity, safety, and pharmacokinetics.

Presented herein is a recombinant OPCML-Fc fusion protein molecule and methods of its use in cancer treatment where the Fc portion of the fusion protein molecule is only the CH2CH3 portion and lacks the hinge region containing the disulfide bridges preventing dimerization of the Fc portion and optimizing dimerization of the OPCML the D1 domain.

The present inventors succeeded in improving the antibody constant region to have increased stability under acid conditions, reduced heterogeneity originated from disulfide bonds in the hinge region, reduced heterogeneity originated from the H chain C terminus, and increased stability at high concentrations as well as in discovering novel constant region sequences having reduced Fcγ receptor-binding, while minimizing the generation of novel T-cell epitope peptides. As a result, the present inventors successfully discovered antibody constant regions with improved physicochemical properties (stability and homogeneity), immunogenicity, safety, and pharmacokinetics.

The invention relates to a novel antibody capable of binding specifically to the human c-Met receptor and / or capable of specifically inhibiting the tyrosine kinase activity of said receptor, with an improved antagonistic activity, said antibody comprising a modified hinge region.The invention also relates to a composition comprising such an antibody antagonist to c-Met and its use as a medicament for treating cancer.

The clinical potential of multispecific antibodies like bispecific and trispecific antibodies shows great promise for targeting complex diseases. However, the generation of those molecules presents great challenges as in many cases it is desired to specifically drive the specific pairing of multiple polypeptide chains that are present in solutions. In the case of the heavy chains, there are two main regions that form a dimer interface. One of them is the CH3 region, which has been widely exploited by inserting either charge-pair mutations (CPMs) to steer the dimer interface or inserting large bulky residues into cavities (Knob in Hole) to physically favor and disfavor the dimer formation. However, each of these strategies may not be applied to every molecule and therefore there is the need for more tools. Here, we describe the engineering of the Hinge region with a small number of mutations that are capable to alone successfully drive the heavy chain dimerization.

The invention provides antibody heavy chain constant regions with a hinge region modified to reduce binding to Fcγ receptors. The modification occurs within positions 233-236 by replacement of natural residues by glycine(s) and / or deletion(s). Such modifications can reduce binding of an antibody bearing such a constant region to Fcγ receptors to background levels. The constant regions can be incorporated into any format of antibody or Fc fusion protein. Such antibodies or fusion proteins can be used in methods of treatment, particularly those in which the mechanisms of action of the antibody or Fc fusion protein is not primarily or at all dependent on effector functions, as is the case when an antibody inhibits a receptor-ligand interaction or agonizes a receptor.

The present disclosure relates to stabilization of Fc-containing polypeptides. The present disclosure provides polypeptides comprising an antibody Fc region that lacks one or more cysteine residues in the hinge region, and one or more CH3 interface amino acids are substituted with thiol group-containing residues. Furthermore, Fc fusion proteins and antibodies containing the polypeptides, nucleic acids and vectors encoding the polypeptides, and host cells and methods for making the polypeptides are provided.

Provided herein are antibodies, recombinant proteins, and methods of use thereof including, for example, immunoglobulin G (IgG) antibodies and recombinant proteins including a Fab region and an Fc region connected through a hinge region, where the hinge region is resistant to cleavage by a protease. Also, provided herein, inter alia, are immunoglobulin G (IgG) antibodies and recombinant proteins including a Fab region and an Fc region connected through a hinge region, and where the Fc region has higher affinity for a ligand compared to a wildtype Fc.

The present invention relates to a trispecific antibody specifically binding to CD19, CD3, and CD28, which trispecific antibody contains a fragment derived from an IgD hinge region as a linker. The present invention also relates to the use of the trispecific antibody for treating tumors such as malignant hematological tumors.

This invention provides a novel antibody with improved thermal stability. [Solution] A modified antibody comprising a polypeptide having a sequence in which at least a portion of amino acid residues are deleted in the hinge region of the antibody.

To provide multispecific antigen binding proteins comprising two distinct heavy chains in the hinge region that utilize charge pair mutations in order to both facilitate heterodimer formation while inhibiting homodimer formation.SOLUTION: Provided is an isolated heteromultimer, comprising: a first immunoglobulin hinge domain polypeptide comprising a plurality of specific amino acid substitutions; and a second immunoglobulin hinge domain polypeptide comprising a plurality of different specific amino acid substitutions.SELECTED DRAWING: Figure 1