159 results about "Constant region" patented technology

Aspects of the disclosure relate to compositions comprising a plurality of complexes comprising an antibody (e.g., anti-TfRI antibody) covalently linked to one or more oligonucleotides (e.g. a DMPK targeting oligonucleotide), each oligonucleotide being covalently linked at a linkage site represented by a lysine (K) residue of the antibody. In some embodiments, the antibody comprises a heavy chain comprising a heavy chain variable region (VH) and a heavy chain constant region, and a light chain comprising a light chain variable region (VL) and a light chain constant region, wherein at least 80% (e.g., 80%-98%, 80%-95%, 80%-90%, 85%-98%, 85%-95%, 85%-90%, 90%-98%, 90%-95%, 95%-97%, or more) of the light chain constant regions of the antibodies of the complexes in the composition are independently covalently linked to an oligonucleotide at a linkage site represented by K188 (based on Kabat numbering) and / or a linkage site represented by K190 (based on Kabat numbering) of the light chain constant regions of the antibodies.

To provide a modified antibody of class IgG for use in radioimmunotherapy.SOLUTION: An anti-PSMA antibody comprises a heavy chain constant region comprising one or more amino acid substitutions compared to a wild-type IgG, wherein the one or more amino acid substitutions reduce the affinity of the antibody for the neonatal Fc receptor (FcRn), thereby reducing the serum half-life of the modified antibody compared to a wild-type antibody of class IgG. The one or more amino acid modifications having the effect of reducing FcRn binding are selected from positions His310, His433, His435, His436, and Ile253. The antibodies of the present invention are particularly suited for use in radioimmunotherapy.SELECTED DRAWING: None

The present invention relates to the field of tumor treatment and immunology biology. Provided are a pharmaceutical combination containing an anti-PD-1-anti-VEGFA bispecific antibody, and the use thereof. Specifically, the pharmaceutical combination comprises at least one bispecific antibody and at least one PARP inhibitor, wherein the bispecific antibody comprises a first protein functional region for targeting PD-1 and a second protein functional region for targeting VEGFA; and according to the EU numbering system, the heavy chain constant region of an immunoglobulin contained in the bispecific antibody is mutated at two sites, i.e. site 234 and site 235, and after mutation, the affinity constant of the bispecific antibody to FcγRI, FcγRIIa, FcγRIIIa and / or C1q is reduced compared with the affinity constant of the bispecific antibody thereto before mutation. The combined administration of the PARPi and the bispecific antibody has a significantly better therapeutic effect on tumors than the individual use of the PARPi or the bispecific antibody; and the present invention has good application prospects.

The disclosure is directed to a heterodimer molecule, comprising a first polypeptide chain and a second polypeptide chain, and the first polypeptide chain comprises a first CH3 domain of an antibody heavy chain constant region, the second polypeptide chain comprises a second CH3 domain of an antibody heavy chain constant region. Comparing to a corresponding wild-type CH3 domain of a human antibody heavy chain constant region, the first CH3 domain and the second CH3 domain comprise specific substitution mutations combination, for example, for the first CH3 domain: T366W+F405K, and for the second CH3 domain: T366S+L368A+Y407V+K409A.

Antibodies, antigen-binding proteins and Fc-fusion proteins that comprise recombinant polypeptides containing a chimeric heavy chain constant region sequence are provided that bind to certain Fc receptors however have reduced effector functions. Methods of making constructs for expression of such chimeric Fc-containing antibodies, antigen-binding proteins and Fc-fusion proteins in cell systems, and methods of producing and isolating the chimeric Fc-containing proteins are provided.

The invention belongs to the technical field of monoclonal antibody preparation, and particularly relates to a human-mouse chimeric monoclonal antibody for resisting human myelin sheath oligodendrocyte glycoprotein (MOG) and application of the human-mouse chimeric monoclonal antibody. Complementary determining regions in variable regions of a heavy chain and a light chain of the human-mouse chimeric monoclonal antibody of the anti-human MOG protein come from a mouse, parent activity is reserved to the maximum extent, a constant region is a human antibody constant region, immunogenicity is greatly reduced due to introduction of the human antibody constant region, the occurrence probability of a human anti-mouse antibody reaction is reduced, and the anti-human MOG protein is prepared. The specificity of the antibody is improved. The human-mouse chimeric monoclonal antibody resisting the human MOG protein has antigen binding specificity, the heterology of a mouse monoclonal antibody is greatly reduced, the biological activity of the human-mouse chimeric monoclonal antibody is good, and the human-mouse chimeric monoclonal antibody resisting the human MOG protein can specifically detect the MOG protein.

The invention discloses an anti-parvovirus canine-mouse chimeric antibody, and belongs to the field of gene engineering, the chimeric antibody comprises a heavy chain variable region, a light chain variable region, a heavy chain constant region and a light chain constant region, the heavy chain variable region and the light chain variable region are mouse-derived fragments, and the heavy chain constant region and the light chain constant region are canine-derived fragments; the amino acid sequence of the heavy chain variable region is as shown in SEQ ID No.2, and the amino acid sequence of the light chain variable region is as shown in SEQ ID No.4. The canine-mouse chimeric antibody has broad-spectrum high neutralization activity on various subtypes of CPV in vitro, the immunological rejection of a mouse antibody in a canine body is reduced, and the canine infected by CPV-2c can be effectively treated by using the canine-mouse chimeric antibody.

The present application relates to the field of medicine, and specifically to a GLP-1 analog fusion protein and its application. The GLP-1 analog fusion protein is obtained by fusing GLP-1 to the N-terminus of the IgG4 heavy chain constant region and the light chain constant region. The results of the study showed that the GLP-1 analog fusion protein of the present application has a significant effect on reducing the weight of mice. The volume and weight of the mouse liver decreased, and the NAS score and hepatic steatosis were significantly improved. Therefore, the present invention can be applied to drugs or products for weight loss or the treatment of fatty liver.

The disclosure relates generally to canine antibody variants and uses thereof. Specifically, the disclosure relates to mutations in the constant region of canine antibody for improving its half-life and other characters.

The invention discloses a bifunctional T cell adapter targeting CD14 and CD3 and an application of the bifunctional T cell adapter. Specifically, the invention provides a CD14 and CD3 targeting bifunctional T cell adapter, the CD14 and CD3 targeting bifunctional T cell adapter comprises a skeleton containing an IgG antibody constant region, the skeleton comprises two heavy chains and a light chain, one heavy chain comprises heavy chain constant regions CH1, CH2 and CH3, the other heavy chain comprises CH2 and CH3, the light chain comprises CL, the CD14 and CD3 targeting bifunctional T cell adapter is a heterotrimer, and the CD14 and CD3 targeting bifunctional T cell adapter is a heterotrimer. Specifically, the first subunit comprises a light chain variable region of an anti-CD14 antibody and a light chain in the skeleton, the second subunit comprises a heavy chain variable region of the anti-CD14 antibody and a heavy chain in the skeleton, and the third subunit comprises a heavy chain variable region of an anti-CD3 antibody and a light chain variable region. The bifunctional T cell adapter disclosed by the invention has an excellent tumor killing effect.

The present disclosure provides editable cell lines, including the use of gene editing proteins to produce the cell lines. The editable cell lines are able to express antibody constant regions that can serve as a platform for the antibody variable regions to produce customized antibody.

The present invention provides a method for generation of multi-domain proteins, more particular antibodies, with an improved native state colloidal stability. The present disclosure provides a method of producing an IgG1 or IgG4 antibody with an improved colloidal stability comprising, in embodiments: calculating for each domain of said IgG1 or IgG4 antibody the total net charge at a given pH; introducing one or more modifications to the amino acid residues of the constant region of saidIgG1 or IgG4 antibody to minimize the charge sign difference between the domains, wherein said one or more modification is, or each are, a substitution of a charged amino acid by a polar (non-charged) amino acid; and producing the modified multi-domain protein with improved colloidal stability at the given pH.

Provided herein are engineered IgA antibodies that comprises: (a) an EGFR binding domain and (b) an IgA heavy chain constant region. Also, provided herein are methods of treating cancer in a subject in need thereof, the method comprising administering to the subject an effective amount of the engineered antibody.

An IgG1 Fc monomer, a preparation method therefor and an application thereof. Causing an Fc dimer of a novel IgG1 Fc monomer sequence for which an antibody IgG1 constant region is modified to become an Fc monomer by means of the modification on a human antibody IgG1 constant region Fc that uses antibody engineering technology, and maintaining an FcRn binding function; the present application has the feature of very low non-specific binding with unrelated proteins, and the main features of the Fc monomer comprise the T366, L368, P395, and K409 positions in a CH3 region of the constant region of the antibody having mutations, and the monomer being highly efficiently expressed in prokaryotic cells; the monomer may bind to FcRn by using a pH-dependent specific binding mode, and has the feature of very low non-specific binding. By using said Fc monomer, the same may be fused or coupled with various proteins, polypeptides, small molecules, nucleic acids and the like for different targets such that the fused or coupled molecules have the feature of being capable of binding to FcRn by using pH dependence.

The present invention provides systems and methods for predicting an allergic response in a subject by measuring the amounts of RNA species from B cells that encode at least a part of the Immunoglobulin E (IgE) constant region (Cε), such as nonproductive epsilon germline transcripts (εGLTs).

The present invention discloses a genetically modified rodent whose immunoglobulin light chain locus is modified so as to comprise a single rearranged human immunoglobulin light chain gene V / J gene upstream of a mouse Kappa light chain locus constant region, a mouse variable region sequence cannot bind to an endogenous constant region to form a complete mouse light chain antibody, the rodents are capable of normally reproducing and producing human light chain-containing antibodies. The invention also provides a method of making the genetically modified rodent and a use of the rodent.

Disclosed is a genetically modified mouse having an immunoglobulin heavy chain locus engineered to insert a gene segment of a human immunoglobulin heavy chain variable region. The mouse is able to reproduce normally and produce a human-mouse chimeric antibody comprising a human heavy chain variable region and a mouse constant region. Also provided is a method for preparing the genetically modified mouse and use of the mouse.

A fusion antibody and its application. The fusion antibody includes: a) IL-15; b) IL-15Ra; and c) an antibody targeting a therapeutically relevant cell surface antigen. The antibody includes a heavy chain variable region (VH), a heavy chain constant region (CH1), a light chain variable region (VL), and a light chain constant region (CL). IL-15 / IL-15Ra is located between the C-terminus of the heavy chain variable region VH and the N-terminus of the heavy chain constant region CH1, and between the C-terminus of the light chain variable region VL and the N-terminus of the light chain constant region CL. This fusion antibody prolongs its half-life and, utilizing its targeting properties, specifically reaches its target site to exert its effect, conferring IL-15 with unique cell targeting properties. It exerts its receptor activation effect only in an environment containing high receptor concentrations of IL-2βγ, thus reducing the systemic toxicity of the IL-15 / IL-15Ra complex.

The invention discloses a human-mouse chimeric monoclonal antibody of GABABR1 protein and a product and application thereof, and belongs to the technical field of monoclonal antibodies, and the human-mouse chimeric monoclonal antibody comprises a mouse light chain variable region VL, a mouse heavy chain variable region VH, a human antibody light chain constant region and a human antibody heavy chain constant region. The mouse light chain variable region VL comprises three light chain complementary determining regions CDR1, CDR2 and CDR3, and the mouse heavy chain variable region VH comprises three heavy chain complementary determining regions CDR1, CDR2 and CDR3. The invention also provides a nucleic acid molecule, a vector and a host cell for coding the antibody, and application of the nucleic acid molecule, the vector and the host cell in preparation of a reagent / kit for detecting GABABR1 protein and a reagent / kit for resisting GABABR antibody-related encephalitis and / or prognosis.

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 application provides a kind of MFGE8 monoclonal antibody and its preparation method and application, the heavy chain and light chain variable region nucleotide sequence of the MFGE8 monoclonal antibody is obtained by constructing rabbit phage library, panning, monoclonal screening and identification, then the heavy chain and light chain variable region nucleotide sequence obtained is respectively subcloned into the expression vector containing IgG constant region nucleotide sequence, is constructed into complete IgG antibody expression vector and is introduced into eukaryotic cell to express and purify, and five strains of monoclonal antibodies with strong affinity are screened out by ELISA experiment.The application also pairs five strains of monoclonal antibodies two by two to screen the antibody pair with the strongest antigen binding capacity, and uses the antibody pair to prepare MFGE8 ELISA detection kit for quantitatively detecting the content of MFGE8 in human biological samples, to assist early diagnosis and screening of breast cancer.

Provided herein is a transgenic chicken comprising a genome having an endogenous immunoglobulin heavy chain gene in which the IgY CH1 coding sequence is functionally deleted. In certain embodiments, in B cells of the chicken the endogenous immunoglobulin heavy chain gene comprises: (a) a functional immunoglobulin heavy chain gene comprising, in operable linkage, a nucleic acid encoding an antibody heavy chain variable domain and a constant region coding sequence in which the IgY CH1 coding sequence is functionally deleted; and (b) a plurality of pseudogenes that are operably linked to said functional immunoglobulin heavy chain gene and that donate, by gene conversion, nucleotide sequence to the nucleic acid encoding the variable domain of (a), wherein the pseudogenes are upstream of the nucleic acid encoding an antibody heavy chain variable domain of (a).

The invention relates to the field of medicine, in particular to fusion protein with GLP and GIP dual activity and application of the fusion protein. The GLP and GIP dual-activity protein in the fusion protein with the GLP and GIP dual-activity is obtained through specific design, and the GLP and GIP dual-activity protein is further fused at the N end of a heavy chain constant region and a light chain constant region of IgG4 or the N end of Fc to obtain the fusion protein with the GLP and GIP dual-activity. Research results show that the fusion protein with GLP and GIP dual activities has an obvious effect of reducing the weight of mice, and the fusion protein can be applied to drugs or products for slimming or treating fatty liver.

The present invention relates to an antibody fragment consisting of only the constant region of an antibody, and more particularly to an antibody fragment having no variable region of an antibody and consisting of only a heavy chain constant region (C H ) and a light chain constant region (C L ). For example, the present invention relates to an antibody fragment consisting of a heavy chain constant region and a light chain constant region (IgCw-gamma1epsilon2-4 / kappa), in which a gamma constant region (Cgamma1) and an epsilon constant region (Cepsilon2-4) are fused; a nucleic acid encoding the antibody fragment; a kit comprising the antibody fragment; and a use of the antibody fragment. In order to evaluate the efficacy of an antibody in the development of a new antibody drug or the like, a control, i.e., a reference antibody, is required, and the existing reference antibody cannot be completely free from non-specific binding, i.e., off-target effects due to reactions with other antigens, and the purification yield is also low. On the other hand, when the recombinant protein IgCw-gamma1epsilon2-4 / kappa consisting of only the constant region of an antibody according to the present invention is used, the problems of the existing reference antibody can be overcome, and the recombinant protein can also be used as an Fc epsilon receptor inhibitor that inhibits an allergic reaction. Therefore, the IgCw-gamma1epsilon 2‑4 / kappa according to the present invention can be used in various ways in the field of biomedical science.

The invention discloses a high-sensitivity wide-spectrum specific antibody for resisting parathion, parathion-methyl and fenitrothion, the high-sensitivity wide-spectrum specific antibody comprises a heavy chain constant region, a heavy chain variable region, a light chain constant region and a light chain variable region, and the amino acid sequence of the heavy chain variable region is as shown in SEQ ID NO: 2; the amino acid sequence of the light chain variable region coding gene is shown as SEQ ID NO: 4. The invention also provides an antibody expression plasmid. The obtained variable region sequence gene is respectively connected to an expression vector containing a heavy chain constant region gene and a light chain constant region gene, and a new recombinant full-length antibody is successfully obtained through an HEK293 (F) mammalian cell expression system. Based on the characteristics of stability and easy preservation of recombinant expression plasmids, the recombinant expression plasmids can be used for multi-batch repeated production of prohibited and limited organophosphorus pesticide recombinant antibodies for resisting parathion and the like; a stable and reliable core reaction reagent is provided for construction of an immunoassay method for multiple residues of organophosphorus pesticides such as parathion in a development environment and a food sample and development of a field screening product.

The helicobacter pylori bispecific antibody comprises a first antibody, a connector and a second antibody, the first antibody (VHH) is specifically combined with a helicobacter pylori urease B subunit (UreB) antigen, the second antibody (ScFv) is specifically combined with a helicobacter pylori vacuolar toxin protein (VacA) antigen, the first antibody (VHH) is connected with the second antibody (ScFv) through the connector, and the second antibody (ScFv) is connected with the second antibody (ScFv) through the connector. The whole or part of the connector is a heavy chain constant region derived from humanized lgG1 or lgG2 or lgG3 or lgG4; the bispecific antibody can significantly reduce adhesion of helicobacter pylori in the stomach, and reduce infiltration of inflammatory cells and damage of stomach tissues; the helicobacter pylori bispecific antibody can quickly and obviously reduce the infection ability of helicobacter pylori, and does not generate other harmful effects on stomach tissues and cells.

This invention provides a fully human anti-H3N2 virus neutralizing antibody IAV-3 and its applications, belonging to the fields of microbiology and immunology. The amino acid sequence of the heavy chain variable region of the neutralizing antibody IAV-3 is shown in SEQ ID NO:1, and the amino acid sequence of the light chain variable region is shown in SEQ ID NO:2; the amino acid sequence of the heavy chain constant region of the neutralizing antibody IAV-3 is shown in SEQ ID NO:3, and the amino acid sequence of the light chain constant region is shown in SEQ ID NO:4. The neutralizing antibody provided by this invention has the characteristics of high expression, fully human origin, and good stability, making it suitable for industrial production and possessing potential application value in responding to current and future influenza caused by the H3N2 virus.

The present invention discloses a monoclonal antibody against porcine SLFN11 protein and its application, relating to the field of biotechnology. The monoclonal antibody against porcine SLFN11 protein comprises a heavy chain variable region with the amino acid sequence shown in SEQ ID NO.1 and a light chain variable region with the amino acid sequence shown in SEQ ID NO.3. The monoclonal antibody has an IgG1 heavy chain constant region and a kappa light chain constant region, exhibiting strong affinity and stability and capable of specifically binding to porcine SLFN11 protein. This invention provides an excellent immunological tool for further exploring the antiviral function and mechanism of the SLFN11 protein, laying the foundation for the development of genetically engineered antibody drugs and novel vaccines for the prevention or treatment of porcine viral diseases.

Non-human animals (and / or non-human cells) and methods of using the same are provided, which non-human animals (and / or non-human cells) have a genome comprising human antibody-encoding sequences (i.e., immunoglobulin genes). Non-human animals described herein express antibodies that are of IgA, IgD, or IgM isotypes. Non-human animals provided herein are, in some embodiments, characterized by expression of IgA antibodies that contain human heavy chain and light chain variable domains and rodent constant domains. Methods for producing antibodies from non-human animals are also provided, which antibodies contain human variable regions and rodent constant regions.

Non-human animals (and / or non-human cells) and methods of using the same are provided, which non-human animals (and / or non-human cells) have a genome comprising human antibody-encoding sequences (i.e., immunoglobulin genes). Non-human animals described herein express antibodies that contain immunoglobulin (Ig) light chains characterized by the presence of human Vλ domains. Non-human animals provided herein are, in some embodiments, characterized by expression of antibodies that contain human Vλ light chains that are encoded by human Igλ light chain-encoding sequences inserted into an endogenous Igκ light chain locus of said non-human animals. Methods for producing antibodies from non-human animals are also provided, which antibodies contain human variable regions and mouse constant regions.