95 results about "Constant region" patented technology

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 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.

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.

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.

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.

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 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.

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.

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 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.

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.

Aspects of the disclosure relate to compositions comprising a plurality of complexes comprising an antibody (e.g., anti-TfR1 antibody) covalently linked to one or more oligonucleotides (e.g. a phosphorodiamidate morpholino oligomer), 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%, or 90%-95%) 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 region of each antibody.

Provided herein are engineered antibodies that comprise a modified IgA heavy chain constant region, pharmaceutical compositions, and methods of use. The engineered antibodies described herein comprise one or more amino acid substitution or deletion in a constant region of an IgA domain. Further provided herein are methods of treating disorders, including cancer, by administering an engineered IgA antibody described herein.

A genetically modified mouse is provided, wherein the mouse is incapable of rearranging and expressing an endogenous mouse immunoglobulin light chain variable sequence, wherein the mouse expresses only one or two human light chain variable domains encoded by human immunoglobulin sequences operably linked to the mouse kappa (κ) constant gene at the endogenous mouse κ locus, wherein the mouse expresses a reverse chimeric antibody having a light chain variable domain derived from one of only two human light chain variable region gene segments and a mouse κ constant domain, and a human heavy chain variable domain and a mouse heavy chain constant domain, from an endogenous mouse heavy chain locus. Bispecific epitope-binding proteins that are fully human are provided, comprising two different heavy chains that associate with an identical light chain that comprises a variable domain derived from one of two different human light chain variable region gene segments.

The application discloses a goat recombinant monoclonal antibody against rabbit IgG and a preparation and application thereof, and belongs to the technical field of biotechnology. The recombinant monoclonal antibody is obtained by taking purified rabbit serum IgG as an immunogen, immunizing a goat, screening specific B cells, and obtaining a heavy chain variable region and a light chain variable region of the antibody through RT-PCR. The variable region sequences are respectively inserted into a vector plasmid with constant region (heavy chain and light chain) genes, and the recombinant monoclonal antibody is obtained through transfection expression and purification. The recombinant monoclonal antibody provided in the application has high affinity with rabbit IgG, can recognize and detect rabbit IgG with high specificity and high sensitivity, and can be used as a secondary antibody after HRP cross-linking, applied to methods such as protein immunoblotting, immunohistochemistry and ELISA for detecting rabbit IgG, is conducive to obtaining more accurate detection and evaluation results, and reduces the interference of detection cost and background signal.

Disclosed are genetically modified rodents whose immunoglobulin heavy chain constant region loci are engineered such that a continuous segment between the CH1 exon and the CH3 exon of the endogenous IgH Gl is retained in the immunoglobulin heavy chain constant region loci of the rodents, but the CH1 exon of the endogenous IgH Gl is not expressed. Also provided are methods of making the genetically modified rodents and uses of the rodents.

Disclosed are bispecific antibodies with heavy chain constant regions having the sequence of an IgG1 constant region with one or more mutations including one or more substitutions that reduce the ability of the heavy chain constant regions to bind to a human Fcγ receptor.

The present invention relates to an antibody comprising an immunoglobulin heavy chain variable region (VH), an immunoglobulin light chain variable region (VL), an immunoglobulin light chain constant region (CL), an immunoglobulin heavy chain constant region (CH), and two sequences encoding peptide linkers (PL1 and PL2), wherein VH is fused to VL through PL1 and CL is fused to CH through PL2, and its uses for therapeutic or diagnostic purposes. The invention further relates to a recombinant nucleic acid molecule encoding said antibody, and an expression cassette, vector, viral particle, host cell, transgenic organism or pharmaceutical composition comprising said recombinant nucleic acid molecule.

This disclosure discloses a method for generating IgG1 antibodies by culturing CHO cells containing / transfected with one or more (exogenous) nucleic acids encoding (and expressing) an antibody, wherein unpaired splicing sites are removed from the nucleic acid encoding a variable domain of the heavy chain, and these unpaired splicing sites are not removed from the nucleic acid encoding a constant region of the heavy chain.

The invention discloses a high-affinity anti-carbendazim monoclonal antibody which 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 a coding gene of the heavy chain variable region is shown as SEQ ID NO: 2; the amino acid sequence of the light chain variable region coding gene is as shown in SEQ ID NO: 4. The invention also discloses a heavy chain expression plasmid of the anti-carbendazim full-length IgG recombinant antibody. The heavy-chain and light-chain variable region gene sequences of the antibody obtained by the invention are respectively connected to expression vectors containing heavy-chain constant region genes and light-chain constant region genes, and the anti-carbendazim full-length IgG recombinant antibody is obtained by adopting mammalian cell expression mediated by a double-plasmid transfection system. Indirect competitive ELISA proves that the expressed recombinant antibody has recognition activity similar to that of a parent monoclonal antibody.

The invention belongs to the technical field of biology, and particularly discloses a TCR / BCR space transcriptome sequencing method. The method is characterized in that a unique space transcriptome chip is adopted, and a capture probe of the chip sequentially comprises a universal sequence 1, a space address code, a unique molecular tag, a universal sequence 2 and a Poly dT sequence; after a cDNA library is constructed by using the chip, cyclizing the cDNA library, so that a spatial address code is physically adjacent to a variable region; and then taking the cyclized DNA as a template, and carrying out multiple PCR amplification by using a primer complementary with the universal sequence 2 and a specific primer aiming at the constant region, so as to enrich a fragment simultaneously containing a complete variable region sequence and a space address code. Through cooperation of chip design and cyclization enrichment, a variable region primer pool is not needed, and the space variable region sequence of the immune receptor can be captured in an unbiased and efficient manner.

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 application relates to a method for preparing a non-human mammal or its offspring and its use, the method comprising the following steps: a step of making the non-human mammal not express or not correctly express the CH1 domain of the IgM heavy chain constant region; and a step of making the non-human mammal not express or not correctly express the CH1 domain when expressing one, two, three, four or more than four genes encoding the IgG heavy chain constant region. The resulting non-human mammal or its offspring can be used to produce heavy chain antibodies. The non-human mammal obtained by the method of the present application does not introduce any exogenous genes encoding antibody heavy chain variable and constant regions, and can directly utilize all VDJ genes encoding antibody heavy chain variable regions in its own genome, thereby producing heavy chain antibodies with better diversity through heavy chain variable region rearrangement.

The hybrid Fc proteins of this invention include IgG and IgM Fc components. The IgG Fc component includes at least a portion of a hinge region and CH2 and CHS regions. The IgM component includes Cμ3 and Cμ4 regions of a Cμ constant region. The hybrid Fc proteins can form duplexes by interchain disulfide bonding between cysteines in their hinge regions. The hybrid Fc proteins can be used for treating immune disorders mediated by endogenous IgG, such as those previously treated with intravenous immunoglobulin.