57 results about "Antibody constant region" patented technology

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 present invention is directed to antibodies, and antigen-binding portions thereof, engineered to introduce amino acids for site-specific conjugation. The invention relates to engineered antibody constant region (Fc, Cγ, Cκ, and Cλ) polypeptides, and portions thereof, and antibodies comprising the polypeptides. Further, the invention relates to Fc fusion proteins comprising an engineered Fc region. The invention also relates to methods and uses of the engineered antibodies and portions for, among other things, production of antibody-drug conjugate therapeutics.

A fusion protein for delivery of a wide variety of agents to a cell via antibody-receptor-mediated endocytosis comprises a first segment and a second segment: the first segment comprising a variable region of an antibody that recognizes an antigen on the surface of a cell that after binding to the variable region of the antibody undergoes antibody-receptor-mediated endocytosis, and, optionally, further comprises at least one domain of a constant region of an antibody; and the second segment comprising a protein domain selected from the group consisting of avidin, an avidin mutein, a chemically modified avidin derivative, streptavidin, a streptavidin mutein, and a chemically modified streptavidin derivative. Typically, the antigen is a protein. Typically, the protein antigen on the surface of the cell is a receptor such as a transferrin receptor-or an insulin receptor. The invention also includes an antibody construct incorporating the fusion protein that is either a heavy chain or a light chain together with a complementary light chain or heavy chain to form an intact antibody molecule. The invention further includes targeting methods and screening methods.

Provided are bispecific antibodies having a full-size antibody portion with two light chains and two heavy chains, wherein the two heavy chains each is fused to a single-chain variable fragment (scFv) portion. In certain embodiments, the full-size antibody has specificity to EGFR and the scFv has specificity to VEGF.

The present invention relates to one or more nucleic acid(s) encoding a binding molecule specifically binding to a human CD28 molecule, comprising (a) a nucleic acid sequence encoding a VH region and a nucleic acid sequence encoding a VL region comprising CDRs in a human immunoglobulin framework, wherein (i) the CDRs of the VH region (CDR-H) comprise the amino acid sequences of SEQ ID NOS: 2 or 18 (CDR-H3), 4 or 20 (CDR-H2) and 6 or 22 (CDR-H1) or are encoded by the nucleic acid sequences of SEQ ID NOS: 1 or 17 (CDR-H3), 3 or 19 (CDR-H2) and 5 or 21 (CDR-H1); and (ii) the CDRs of the VL region (CDR-L) comprise the amino acid sequences of SEQ ID NOS: 8 or 24 (CDR-L3), 10 or 26 (CDR-L2) and 12 or 28 (CDR-L1) or are encoded by the nucleic acid sequences of SEQ ID NOS: 7 or 23 (CDR-L3), 9 or 25 (CDR-L2) and 11 or 27 (CDR-L1); and (b) a nucleic acid sequence encoding the constant region of a human IgG1 or IgG4 antibody.

The present invention provides methods of creating and using OB protein compositions with an antibody constant region or portion thereof fused to an OB protein. The fusion protein is created by attaching the polyamino acids to the OB protein moiety. The fusion proteins can then be used for various therapeutic uses.

By altering amino acid sequences, the present inventors successfully produced constant regions that can confer antibodies with particularly favorable properties for pharmaceutical agents. When used to produce antibodies, the altered constant regions produced according to the present invention significantly reduce heterogeneity. Specifically, the antibody homogeneity can be achieved by using antibody heavy chain and light chain constant regions introduced with alterations provided by the present invention. More specifically, the alterations can prevent the loss of homogeneity of antibody molecules due to disulfide bond differences in the heavy chain. Furthermore, in a preferred embodiment, the present invention can improve antibody pharmacokinetics as well as prevent the loss of homogeneity due to C-terminal deletion in antibody constant region.

The present inventors devised methods for efficiently purifying bispecific antibodies using a chromatography column based on the difference in isoelectric points between the H chains of two types of antibodies, wherein the difference is introduced by modifying the amino acids present on the surface of the antibody variable regions of two types of antibodies that constitute a bispecific antibody. Furthermore, the inventors devised methods for efficiently purifying bispecific antibodies using a chromatography column by linking respective antigen binding sites (heavy chain variable regions) to the antibody constant regions having different isoelectric points, and then coexpressing these antibodies.

Methods of identifying and expressing an antibody variant are disclosed wherein the method comprises identifying a binding region in an antibody, fusing the binding region to a plurality of scaffolds of antibody constant regions to obtain antibody fragment variants, expressing the antibody fragment variants in organisms to form constructs and expressing the constructs carried by the organisms to form induced cultures, wherein the organisms are expressed in HTP mode.

The invention belongs to the technical field of biology, and particularly relates to an IgG1Fc monomer and a preparation method and application thereof. In accordance with the sequence of a novel IgG1Fc monomer reformed in an antibody IgG1 constant region, through an antibody engineering technique, a human antibody IgG1 constant region Fc is reformed, so that an Fc dipolymer becomes an Fc monomer,an FcRn combination function is maintained, and an extremely low irrelevant protein non-specific combination characteristic is achieved; main features of the Fc monomer lie in that the Fc monomer hasmutation at positions of T366, L368, P395 and K409 in a CH3 region of the antibody constant region, has high-efficiency expression in prokaryotic cells, can use combination of a pH dependent specialcombination mode with FcRn, and has extremely low nonspecific combination characteristics. Through the novel Fc monomer, the IgG1Fc monomer can fuse or couple with various protein, polypeptide, micromolecules, nucleic acid and the like for different target points, so that fused or coupled molecules have the characteristic of combining pH dependence with FcRn.

The present invention discloses an agonistic antibody directed against human thrombopoietin receptor (also referred to as 'human c-Mpl). Specifically, the antibody has a constant region having a set of amino acid sequences selected from the following items (1) to (3): (1) amino acid sequences for a heavy-chain constant region and a light-chain constant region of a human antibody; (2) an amino acid sequence for a human antibody heavy-chain constant region in which the domain is replaced by one of other human antibody subclass and an amino acid sequence for a human antibody light-chain constant region; and (3) a set of amino acid sequences having the deletion, substitution, addition or insertion of one or several amino acid residues in each of the amino acid sequences shown in (1) and (2), and the antibody has a variable region capable of binding to a human thrombopoietin receptor to activate the receptor. The antibody also has the following properties: (a) the antibody can induce the formation of a colony at a concentration of 10,000 ng/mL or less in the CFU-MK colony formation assay using a human umbilical cord blood CD34+ cell; and (b) the antibody has the maximum activity higher than that of PEG-rHuMGDF by 50% or more and a 50% effective concentration (EC50) of 100 nM or less in the cell growth assay using an UT7/TPO cell. Also disclosed is a pharmaceutical composition for the treatment of thrombocytopenia, which comprises the antibody.

The invention discloses an anti-staphylococcus aureus alpha-hemolysin single-chain antibody scFv2 or scFv46, further discloses an anti-staphylococcus aureus alpha-hemolysin recombinant antibody scFv2-Fc or scFv46-Fc containing the scFv2 or scFv46 and a human antibody constant region Fc segment amino acid sequence, and further discloses a universal expression vector sp-Fc/pcDNA3.1 of the fully human anti-staphylococcus aureus alpha-hemolysin recombinant antibody. The nucleic acid sequence of an encoding gene of the universal expression vector is shown in SEQ ID No:13. The invention further discloses a eukaryotic expression vector of the fully human anti-staphylococcus aureus alpha-hemolysin recombinant antibody. The eukaryotic expression vector is obtained by inserting the single-chain antibody into the sp-Fc/pcDNA3.1. The invention further discloses a recombinant expression vector sp-scFv2-Fc/pMH3 or sp-scFv46-Fc/pMH3.