25 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.

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.

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.

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.

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.

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.

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.

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 are chimeric antigen receptors (CARs) having antigenic specificity for human gamma-delta (γδ) T cell receptor (TCR) constant domain. Also provided are related nucleic acids, recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions relating to the CARs. Methods of treating or preventing a condition in a mammal are also provided.

The present invention provides molecules, including proteins, more particularly, immunoglobulins whose in vivo half-lives are altered (increased or decreased) by the presence of an IgG constant domain, or FcRn binding fragment thereof (e.g., an Fc region or hinge-Fe region) (e.g., from a human IgG, e.g., human IgG1), that have modifications of one or more of amino acid residues in at least the CH3 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.

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

The present disclosure related to chimeric antigen receptors (CARs) comprising immunoglobulin (Ig) derived spacers, e.g., hinge or loop regions, fragments thereof, or combinations thereof. Ig derived spacer confers improved properties to the CARs, e.g., increased cytokine release with respect the CARs with spacers not derived from hinge regions and fragments thereof, loop regions from constant domains and fragments thereof, and combinations thereof. Also provided are cells expressing CARs comprising Ig derived spacers regions and methods to use the CARs to treat diseases or disorders, e.g., cancer. Some of the disclosed Ig derived spacers are fragments from, e.g., IgAQ1, IgA2, IgD, IgE, IgG1, IgG2, IgG3, IgG4, or IgM. In some aspects, the disclosed Ig derived spacers are derived from non-human immunoglobulins, e.g., mouse immunoglobulins such IgG2A. Other Ig derived spacer disclosed are modular constructs comprising several concatenated Ig hinges or fragments thereof.

This invention relates to immunoconjugates, particularly immunoconjugates comprising an antibody or antigen-binding fragment thereof comprising a first antibody binding domain that specifically binds to one or more constant domains of a gamma delta T-cell receptor (gdTCR) or a fragment or fragments thereof, and at least one IL-15 receptor alpha (CD215) or a functional fragment thereof. The invention also relates to immunoconjugates comprising a multispecific antibody or antigen-binding fragment thereof which further comprises a second antibody binding domain that specifically binds to a second, different target antigen than the first antibody binding domain, such as a tumor associated antigen (TAA). Additionally, this invention relates to polynucleotide molecules encoding said immunoconjugates. It also relates to vectors containing such polynucleotides and host cells comprising such polynucleotides and methods of producing said immunoconjugates. The invention also relates to methods using said immunoconjugates, such as methods treating disease using said immunoconjugates and medicaments comprising or derived from said immunoconjugates.

The present application provides heteromultimeric proteins, such as bispecific antibodies, comprising a first antibody heavy chain constant domain 3 (CH3)-containing polypeptide having a substitution relative to a wildtype CH3 domain at amino acid position 354 with a bulky hydrophobic amino acid, and / or a second CH3-containing polypeptide comprising a substitution relative to a wildtype CH3 domain at ammo acid position 347 with a negatively charged amino acid residue. Also provided are polypeptides, nucleic acids and vectors encoding such polypeptides, pharmaceutical compositions, methods of preparation and methods of treatment using the heteromultimeric proteins.

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.

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.