43 results about "Constant domain" 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 present technology provides polypeptides comprising a first immunoglobulin single variable domain (ISVD) binding to albumin, a second ISVD capable of binding to both the constant domain of a human T cell receptor (TCR) on a T cell and the constant domain of a non-human primate TCR on a T cell, wherein said first and second ISVD are linked by a protease cleavable linker, and a targeting moiety. The present technology further provides nucleic acids encoding said polypeptides as well as vectors, hosts and methods to produce these polypeptides. Moreover, the present technology relates to methods for treatment making use of the polypeptides according to the present technology.

Provided and exemplified herein are antibodies and antibody fragments that bind an IgE constant domain.

The invention relates to screening methods. In particular, it relates to a method of identifying a functional TCR from a library of particles, which displays a plurality of different T cell receptors (TCRs). The method may comprise a) exposing the library of particles to a target antigen to identify TCRs that bind to the target antigen, b) transfecting a plurality of T cells with nucleic acid encoding TCRs identified in step (a), c) exposing the plurality of transfected cells to the target antigen, and d) selecting cells having TCR activity in the presence of the target antigen. Transfection of the T cells is such that each T cell comprises a nucleic acid encoding a single TCR from the library of particles, the nucleic acid is integrated into the genome of the T cell at a single identical pre-defined locus, and the TCR is in a single chain format and comprises an alpha chain variable domain, a beta cain variable domain and a constant domain. The T cells do not express endogenous TCR. A T-cell comprising a recombinase mediated landing pad, wherein the T cell constitutively expresses TCR constant domain and does not express endogenous TCR, is also claimed.

The present invention provides a method of modulating a molecular mass of a fusion polypeptide, wherein the fusion polypeptide comprises a target polypeptide fused to a tag suitable for affinity purification or detection of the target polypeptide, wherein the tag comprises at least one constant domain of an immunoglobulin light chain or orthologous polypeptide or fragment thereof and wherein the molecular mass and / or an isoelectric point of the fusion polypeptide is modulated by increasing the molecular mass of the tag via combining the one constant domain of an immunoglobulin light chain or orthologous polypeptide or fragment thereof with one or more further constant domain(s) of an immunoglobulin light chain or orthologous polypeptide(s) or fragment(s) thereof; wherein the constant domain of the immunoglobulin light chain or orthologous polypeptide or fragment thereof of the tag is monomeric; and wherein optionally the target polypeptide is fused to the tag via a first linker. The invention further provides a fusion polypeptide obtained or obtainable by this method. The invention also provides a tag and a fusion polypeptide comprising the tag.

Genetically modified non-human animals and methods and compositions for making and using them are provided, wherein the genetic modification comprises a deletion in an immunoglobulin constant region CH1 gene (optionally a deletion in a hinge region) of an IgG, IgA, IgD, and / or IgE, and wherein the mouse is capable of expressing a functional IgM. Genetically modified mice are described, including mice having a functional IgM gene and modified to have a deletion of a CH1 domain and a hinge region in a heavy chain constant domain that is not an IgM, e.g., in an IgG heavy chain constant domain. Genetically modified mice that make human variable / mouse constant chimeric heavy chain antibodies (antibodies that lack a light chain), fully mouse heavy chain antibodies, or fully human heavy chain antibodies are provided.

The present application relates to antibody molecules that bind both PD-L1 and CD137 and are able to induce agonism of CD137. The antibody molecules comprise a CDR-based binding site for PD-L1, and a CD137 antigen-binding site that is located in a constant domain of the antibody molecule. The antibody molecules of the invention find application, for example, in the treatment of diseases, such as cancer.

Provided and exemplified herein are antibodies and antibody fragments that bind an IgE constant domain.

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 invention relates to the field of modified constant domains of canine or feline antibodies with altered immune effector functions and uses thereof. More specifically, the present application relates to modified Fc fragments with significantly reduced FcyRI and Clq binding.

This disclosure relates to an immunoglobulin molecule having multiple variable domains that are each specific for a receptor, as well as heterodimeric molecules that include the multivariable domain immunoglobulin and a second heavy chain constant domain (HCCD2) of an antibody comprising a CH1 and a second Fc region (FC2), where FC1 and FC2 heterodimerize.

The application relates to specific binding members that bind OX40. The specific binding members comprise an OX40 antigen-binding site located in a constant domain of the specific binding member and find application in the treatment of cancer and infectious diseases, for example.

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 disclosure provides nucleic acid constructs comprising a transmembrane reporter cassette encoding an affinity tag, a transmembrane (TM) domain and a fluorescent reporter protein. In embodiments, the nucleic acid constructs are inserted in a safe harbor locus or an immunoglobulin constant domain locus of in a cell of a non-human mammal. In embodiments, when the transmembrane reporter cassette is expressed in the cell, the affinity tag is displayed on a surface of the cell while the fluorescent reporter protein is located inside the cell membrane. The presence of the affinity tag and the fluorescent reporter protein allow for identification, sorting and / or isolation of cells expressing the nucleic acid constructs. The disclosure also provides embodiments of methods of modifying cells and non-human organisms with the nucleic acid constructs, along with embodiments of cells and non-human organisms produced using the disclosed methods.

In one aspect, the present invention provides heterodimeric antibodies comprising a first monomer comprising a first heavy chain constant domain comprising a first variant Fc domain and a first antigen binding domain and a second monomer comprising a second heavy chain constant domain comprising a second variant Fc domain and a second antigen binding domain. In an additional aspect the heterodimeric antibody comprises a first monomer comprising a heavy chain comprising a first Fc domain and a single chain Fv region (scFv) that binds a first antigen, wherein the scFv comprises a charged scFv linker. The heterodimeric antibody further comprises a second monomer comprising a first heavy chain comprising a second Fc domain and a first variable heavy chain and a first light chain.

This invention relates to human antibodies and antigen-binding fragments thereof that specifically bind to one or more constant domains of a gamma delta T-cell receptor (gdTCR) or a fragment or fragments thereof. The invention also relates to novel recombinant antigens, particularly novel recombinant and / or isolated antigens comprising one or more constant domains of a gamma delta T- cell receptor (gdTCR) or a fragment or fragments thereof and antibodies that bind said antigens. Further, this invention relates to methods employing said recombinant antigens to obtain said antibodies that specifically bind to and selectively target the constant regions of a gdTCR or fragment thereof. This invention additionally relates to methods for producing and purifying said antibodies and recombinant antigens. Additionally, this invention relates to polynucleotide molecules encoding said antibodies and said recombinant antigens. It also relates to vectors containing such polynucleotides and host cells comprising such polynucleotides and methods of producing said antibodies and antigen- binding fragments. The invention also relates to methods using said antibodies, such as methods of detecting, diagnosing and treating disease using said antibodies and medicaments comprising or derived from said antibodies.

Multifunctional molecules that include i) an antigen binding domain that binds to a T cell receptor beta chain constant domain 1 or T cell receptor beta chain constant domain 2; and one, two or all of: (ii) an immune cell engager (e.g., chosen from an NK cell engager, a T cell engager, a B cell engager, a dendritic cell engager, or a macrophage cell engager); (iii) a cytokine molecule or cytokine inhibitor molecule; (iv) a death receptor signal enhancer; and / or (v) a stromal modifying moiety are disclosed. Additionally disclosed are nucleic acids encoding the same, methods of producing the aforesaid molecules, and methods of treating a cancer using the aforesaid molecules.

To provide multispecific antibodies that heterodimerize in a specific and stable manner and can target multiple antigens correctly.SOLUTION: Provided is a heterodimeric protein comprising a first polypeptide comprising a first immunoglobulin heavy chain constant domain 3 (CH3 domain) and a second polypeptide comprising a second CH3 domain, as well as comprising polypeptides having CH3 domains with engineered residues that form disulfide bonds and / or salt bridges.SELECTED DRAWING: None

A method for combining restrictive proteolysis and immunoassays to specifically detect and quantify amyloid-genic XFLC in a biological fluid. This method is accomplished by the use of mAbs that enable the detection and quantification of neoepitopes on dLCCD biomarkers produced after restricted proteolysis of ZFLC, which is very advantageous for kinetically unstable or amyloid-genic LFLC. The methods do not depend on FLC primary sequences in variable and constant domains, and can be used to detect and quantify up to 99% of human XFLC. The clinical utility of the assay includes early detection in individuals suspected of having plasma cell disorders (MGUS, SMM, MM, IgM-AL and AL), differentiation from other amyloidosis such as ATTR, use in companion diagnosis, proving of target conjugation, assessment of treatment response, detection of MRD, detection of recurrence. Assays, such as MSD, lateral flow, mass spectrometry, are also implemented that quantify the resulting dLCCD biomarkers and / or can further increase assay sensitivity.

The present technology provides polypeptides comprising a first immunoglobulin single variable domain (ISVD) binding to albumin, a second ISVD capable of binding to both the constant domain of a human T cell receptor (TCR) on a T cell and the constant domain of a non-human primate TCR on a T cell, wherein said first and second ISVD are linked by a protease cleavable linker, and a targeting moiety. The present technology further provides nucleic acids encoding said polypeptides as well as vectors, hosts and methods to produce these polypeptides. Moreover, the present technology relates to methods for treatment making use of the polypeptides according to the present technology.

Antibodies comprising unpaired variable domains, e.g., heavy chain variable (VH) domains, for binding antigen. Antibody comprising two immunoglobulin (Ig) chains, wherein a first Ig chain comprises a variable domain and a constant domain, and a second Ig chain comprises a constant domain, wherein the second Ig chain lacks a variable domain, leaving the variable domain of the first Ig chain unpaired. The antibody may comprise two Ig heavy chains and two Ig light chains, each heavy chain comprising a VH domain and a constant region comprising a CH1 domain, and each light chain comprising a CL domain, wherein one or both light chains lack a VL domain, thereby leaving one or both VH domains unpaired. Non-human animals (e.g., mice) engineered to produce antibodies having unpaired VH domains, involving deletion of sequence coding for light chain variable (VL) domains. Use of unpaired VH domains to generate antigen-binding molecules.

In certain aspects, the present disclosure provides a stable liquid pharmaceutical formulation comprising a recombinant fusion protein comprising the extracellular domain (ECD) of human activin receptor type IIA (ActRIIA) protein or a variant thereof linked to a constant domain of an immunoglobulin, such as a human IgG1 Fc domain, and one or more pharmaceutical additives and / or excipients.

In certain aspects, the present disclosure provides stable liquid pharmaceutical formulations comprising a recombinant fusion protein and one or more pharmaceutical additives and / or excipients, the recombinant fusion protein comprises an extracellular domain (ECD) of a human activin receptor type IIA (ActRIIA) protein or a variant thereof linked to a constant domain of an immunoglobulin, such as a human IgG1 Fc domain.

This immunoassay method comprises: a step for detecting a signal corresponding to the concentration or titer of an antigen contained in a biological sample; and a step for calculating the concentration or titer of the antigen in the biological sample from the signal by using a calibration curve indicating the correlation between the signal and the concentration or titer of the antigen. The calibration curve is created using a standard sample containing a fusion protein. The fusion protein has an amino acid sequence of at least a portion of the antigen and an amino acid sequence of at least a portion of the constant domain of immunoglobulin.

Provided and exemplified herein are antibodies and antibody fragments that bind an IgE constant domain.

The invention provides an antibody comprising human IgG1 or IgG3 heavy chain constant domains that are glycosylated with a sugar chain at Asn297, said antibody being characterized in that the amount of fucose within said sugar chain is at least 99%, and in addition the amount of NGNA is 1% or less and / or the amount of N-terminal alpha 1,3 galactose is 1% or less, and uses thereof.

This invention relates to human antibodies and antigen-binding fragments thereof, including multispecific antibodies, that specifically bind to one or more constant domains of a gamma delta T- cell receptor (gdTCR) or a fragment or fragments thereof. The invention also relates to novel recombinant antigens, particularly novel recombinant and / or isolated antigens comprising one or more constant domains of a gamma delta T-cell receptor (gdTCR) or a fragment or fragments thereof and antibodies that bind said antigens. Further, this invention relates to methods employing said recombinant antigens to obtain said antibodies that specifically bind to and selectively target the constant regions of a gdTCR or fragment thereof. This invention additionally relates to methods for producing and purifying said antibodies and recombinant antigens. Additionally, this invention relates to polynucleotide molecules encoding said antibodies and said recombinant antigens. It also relates to vectors containing such polynucleotides and host cells comprising such polynucleotides and methods of producing said antibodies and antigen-binding fragments. The invention also relates to methods using said antibodies, such as methods of detecting, diagnosing and treating disease using said antibodies and medicaments comprising or derived from said antibodies.

The present invention provides cells, transgenic animals, including transgenic mammals and particularly rodents comprising engineered immunoglobulin (Ig) alleles. Such engineered alleles, wherein an Ig light chain CL exon [Cκ or Cλ (Cλ1, Cλ2 or Cλ3)] is incorporated into the Ig heavy chain locus, are capable of producing heavy chain-only antibodies as a single chain VH antibody (scVHAb) or heavy chain antibody (HCAb) comprising two extended scVHAbs. The scVHAb comprises an antigen-binding part consisting of a VH domain and the immunoglobulin constant domains CL, which is either Cκ or Cλ, and CH1, in the orderfrom N-terminus to C-terminus: VH-L1-CL-L2-CH1, wherein L1 and L2 are each, independently, peptidic linkers; and wherein CL is paired with CH1 through beta-sheet contact thereby obtaining a CL / CH1 dimer.

Provided and exemplified herein are antibodies and antibody fragments that bind an IgE constant domain.