15 results about "Constant region" patented technology

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.

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 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.

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.

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.

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.

The invention relates generally to canine antibody variants and uses thereof. Specifically, the invention relates to mutations in the constant region of canine antibody for improving various characteristics.

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

The present invention relates to a heavy chain-based fusion protein and, specifically, to a fusion protein comprising a CH1 domain of IgG and one or more Fc regions selected from IgG and IgE, and to a method for producing same. The fusion protein according to the present invention is capable of forming a structure consisting solely of heavy chains by a light chain constant region variant, and can be produced stably and at a high yield. In addition, the fusion protein of the present invention is capable of forming constructs in combination with various known or newly developed antibodies or fragments thereof. Such constructs may be implemented in various forms, such as monospecific antibodies, bispecific antibodies or heterodimeric antibodies, and may be modified and produced according to the purpose or use. Furthermore, the fusion protein of the present invention may be utilized for the treatment of autoimmune diseases, immunological analysis or as a reference antibody, etc., by leveraging the immunoregulatory functions mediated by IgG or IgE heavy chain constant regions.

Non-human animals (and / or non-human cells) and methods for using said non-human animals (and / or non-human cells) are provided, said non-human animals (and / or non-human cells) having a genome containing sequences encoding human antibodies (i.e., immunoglobulin genes). The non-human animals described herein express antibodies containing immunoglobulin (Ig) light chains, said immunoglobulin light chains being characterized by the presence of a human Vλ domain. In some embodiments, the non-human animals provided herein are characterized by expressing antibodies containing a human Vλ light chain encoded by a sequence encoding a human Igλ light chain inserted into an endogenous Igκ light chain locus of said non-human animal. Methods for producing antibodies from non-human animals are also provided, said antibodies containing a human variable region and a mouse constant region.

Described herein are immunoconjugates comprising an: a) antigen binding region; b) an immunoglobulin heavy chain constant region; and c) a radioisotope chelating agent; wherein the molecular weight of said immunoconjugate is between 60 and 110 kDa. The immunoconjugates can be used to deliver alpha and beta emitters for the treatment of tumors or cancer.

This disclosure provides an IgM antibody or IgM-like antibody comprising a variant J-chain and / or variant IgM heavy chain constant regions that can confer increased serum half-life upon the antibody.

Provided herein are therapeutic agents, pharmaceutical compositions, and methods comprising an IgA constant region. The compositions and methods described herein facilitate binding of an antibody construct comprising an IgA constant domain to CD47 and an antigen for instance a tumor related antigen such as CD20 or CD19.

This document relates to methods and materials involved in producing antibodies (e.g., single domain antibody (sdAbs) and / or heavy chain only antibodies) having one or two chimeric heavy chains. For example, (A) genetically engineered non-human animals (e.g., genetically engineered mice) having the ability to produce an antibody having one or two chimeric heavy chains that include (1) a non-human Ig heavy chain constant domain (CH) 2 and / or a non-human CH3 domain and (2) a VH domain such as a VH domain set forth in any one of SEQ ID NOs:74-87. (B) genetically engineered non-human animals (e.g., genetically engineered mice) having the ability to produce antibody-like molecules that include (1) a non-human heavy chain constant (CH) 2 domain and / or a non-human CH3 domain (e.g., endogenous CH2 and / or CH3 domains) and (2) a TCR variable domain (e.g., a human TCR variable domain). (C) genetically engineered non-human animals (e.g., genetically engineered mice) having the ability to produce antibody-like molecules that include (a) a first amino acid sequence of a FN3 polypeptide (e.g., a 10FN3 polypeptide). (b) a human Ig variable D domain, (c) a second amino acid sequence of a FN3 polypeptide (e.g., a 10FN3 polypeptide), and (d) a non-human Ig heavy chain CH2 domain and / or a non-human CH3 domain (e.g., endogenous Ig CH2 and / or CH3 domains), (D) genetically engineered non-human animals (e.g., genetically engineered mice) having the ability to produce an antibody having one or two chimeric heavy chains that include (a) a non-human Ig heavy chain constant domain (CH) 2 and / or a non-human CH3 domain and (b) a variable region that includes a human JH domain (e.g., a human JH3 domain or a human JH4 domain) lacking all or at least one tryptophan amino acid residue(s), and (E) genetically engineered non-human animals (e.g., genetically engineered mice) having the ability to produce an antibody having a modified heavy chain including (a) a non-human CH2 domain and / or a non-human CH3 domain (e.g., endogenous CH2 and / or CH3 domains) and (b) a variable region that includes a human VH domain having a FR2 containing one, two, three, four, or more amino acid are provided. In addition, chimeric non-human animals (e.g., mice) generated from an embryo having (a) a first cell having one or more genomic modifications that prevent the first cell (and cells derived from the first cell) from producing immunoglobulins and (b) a second cell having an IgH locus that includes an exogenous nucleic acid sequence encoding a heavy chain variable region of an antibody of interest such that the chimeric non-human animal produces heavy chain antibodies containing the heavy chain variable region of the antibody of interest in addition to one or more variants of those heavy chain antibodies that underwent in vivo affinity maturation are provided.

This invention discloses an in vitro detection method and kit for assisting in the screening of systemic lupus erythematosus (SLE) patients suitable for BCMA-CD19 dual-target CAR-T therapy. Based on single-cell transcriptome sequencing, this invention identifies a plasma cell subset that exhibits high XBP1 / JCHAIN ​​expression but low CD19 expression after CD19 single-target therapy. This method uses qPCR to quantitatively detect the mRNA levels of AIM2, XBP1, JCHAIN, and immunoglobulin heavy chain constant region genes in PBMCs, and calculates the BCR category switching score using an exponential operational model. Patients exhibiting high expression of AIM2 or plasma cell markers and a BCR score >1.5 (indicating IgG / IgA dominance) are considered suitable for dual-target therapy. This method effectively identifies individuals at risk of single-target therapy escape and can be used to assess the quality of immune reconstitution after treatment.