293 results about "Hinge region" patented technology

The invention relates to novel binding domain-immunoglobulin fusion proteins that feature a binding domain for a cognate structure such as an antigen, a counterreceptor or the like, a hinge region polypeptide having either zero or one cysteine residue, and immunoglobulin CH2 and CH3 domains, and that are capable of ADCC and/or CDC while occurring predominantly as monomeric polypeptides. The fusion proteins can be recombinantly produced at high expression levels. Also provided are related compositions and methods, including immunotherapeutic applications.

This invention relates to the field of recombinant antibody technology. It provides novel recombinant IgY antibody constructs for diagnostic and therapeutical applications. The bivalent antibody constructs display a heterotetrameric or homodimeric format stabilized by disulfide bonds. The constant heavy chain domains C_H2-C_H4 are partly or completely of avian origin, whereas the V_H, V_L, C_L, and C_H1 domains as well as the hinge region may be of avian origin or derived from any other species. The invention allows to combine the advantages of IgY antibodies with those of established mammalian monoclonal antibodies. IgY antibody constructs comprising nonglycosylated IgY constant heavy chain domains allow to reduce unwanted interactions with C-type lectins, e.g., in human sera. Furthermore, chimeric IgY antibody containing mammalian V_H, V_L, C_L, and C_H1 domains as well as a mammalian hinge region provide a higher molecular stability than IgY antibodies in acidic conditions and, thereby, are especially suited for peroral therapeutic applications.

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.

A mutant of a potentially therapeutic anti-CD40 antibody is provided which mutant has reduced ADCC and CDC activities designed to be optimized as a pharmaceutical agent. A mutant of an agonistic anti-CD40 antibody, comprising mutation and/or substitution of at least one amino acid in the constant region to reduce the ADCC and/or CDC activities therein, and a mutant of an antagonistic anti-CD40 antibody, comprising at least one mutation or substitution in the constant region to reduce the ADCC and/or CDC activities therein, both mutants having at least a hinge region derived from a human IgG2.

The present invention is generally directed to methods of producing an increase in the enrichment and/or recovery of preferred forms of monoclonal antibodies. More particularly, the invention relates to methods for eliminating disulfide heterogeneity in the hinge region of recombinant IgG2 antibody proteins.

The present invention provides stabilized immunoglobulin molecules that have increased storage stability and/or in vivo half-lives due to the mutation of one or more amino acids that would otherwise render the immunoglobulin molecules susceptible to degradation. In a preferred embodiment, the stabilized immunoglobulins of the invention have mutations at the heavy chain constant domain hinge region. Such stabilized immunoglobulin molecules, i.e., immunoglobulin molecules with increased storage stability have one or more of the following advantages they are more readily transported and/storable for longer periods and/or less stringent conditions than non-stabilized counterparts; that smaller amounts and or less frequent dosing is required in the therapeutic, prophylactic or diagnostic use of such stabilized molecules.

System, including methods, apparatus and components thereof, and kits, for connecting to bone using an anchor element configured to be anchored in bone and having a selectively bendable hinge region. In some embodiments, the system may connect the anchor element to connective tissue, a bridge member, and/or to another anchor element by bending the hinge region while the anchor element is disposed in bone, thereby connecting bone to the connective tissue or bridge member, and/or connecting bone members.

Disclosed are concatameric proteins comprising two soluble domains, in which the C-terminus of a soluble domain of a biologically active protein is linked to the N-terminus of an identical soluble domain or a distinct soluble domain of a biologically active protein. Also, the present invention discloses dimeric proteins formed by formation of intermolecular disulfide bonds at the hinge region of two monomeric proteins formed by linkage of a concatamer of two identical soluble extracellular regions of proteins involving immune response to an Fc fragment of an immunoglobulin molecule, their glycosylated proteins, DNA constructs encoding the monomeric proteins, recombinant expression plasmids containing the DNA construct, host cells transformed or transfected with the recombinant expression plasmids, and a method of preparing the dimeric proteins by culturing the host cells. Further, the present invention discloses pharmaceutical or diagnostic compositions comprising the dimeric protein or its glycosylated form.

Luminal prostheses comprise adjacent expansible segments, typically serpentine ring segments joined by sigmoidal links. By properly orienting the sigmoidal links and aligning hinge regions on adjacent serpentine rings, enhanced performance can be obtained.

The invention provides compositions and methods for inhibiting fractionation of immunoglobulins comprising a lambda light chain based on the observation that iron, in the presence of histidine, results in increased fragmentation of a recombinant fully human IgG molecule containing a lambda light chain due to cleavage in the hinge region. The invention further provides an aqueous pharmaceutical formulation comprising an antibody, or antigen-binding portion thereof, that binds the p40 subunit of IL-12/IL-23 and a buffer system comprising histidine, wherein the formulation has enhanced stability, including enhanced resistance to fragmentation.

Illuminated novelty eye glasses include a frame having a body with portions that define lens openings and adjacent hinge regions, and a bridge region between the portions defining the lens openings. The body has a channel formed therein traversing around the lens openings and across the bridge region. The body is formed from a transparent or translucent material. Ear pieces are connected to the frame at the hinge regions. The ear pieces each have a hinge region for hingedly connecting the ear pieces to the body such that the ear pieces fold inwardly toward the body. The ear pieces each include a compartment and a channel extending generally from the compartment to the hinge region. An LED assembly is formed from a plurality of light emitting diodes mounted to a plurality of conductors. A power source is operably connected to the LED assembly and is carried in one of the ear piece compartments and a switch operably connects the power source to the LED assembly and is carried in the other ear piece compartment. The LED assembly is disposed in the channel in the frame and in the ear pieces and the light emitting diodes are illuminated by actuation of the switch. Light from the light emitting diodes is transmitted by the diodes and is visible through the frame and ear pieces.

The invention relates to a chimeric antigen receptor of a targeted GPC3 (Glypican 3) and an application thereof. Specifically, the invention provides a polynucleotide sequence, wherein the polynucleotide sequence is selected from: polynucleotide sequences (1) containing a coding sequence of a CD8 antigen leading peptide, a coding sequence of an anti-GPC3 single-chain antibody, a coding sequence of a human CD8 alpha hinge region, a coding sequence of a human CD8 transmembrane region, a coding sequence of a human 41BB intracellular region, and a coding sequence of a human CD3 zeta intracellular region, and a coding sequence of an optional fragment of an EGFR (Epidermal Growth Factor Receptor) sequence containing an extracellular domain III and an extracellular domain IV, wherein the coding sequences are sequentially connected; and complementary sequences (2) of the polynucleotide sequences (1). The invention provides a CAR (chimeric antigen receptor) coded by the polynucleotide sequences and a T cell expressing the CAR. The prepared CAR-T cell has a function of strongly killing a specific tumor cell, and the kill effectiveness is more than 90% under the condition that the effector-target ratio is 20:1.

A surgical tool for measuring a heart that includes two handle members, and a flexible member. The handle members are configured with internal passageways to allow the flexible members to pass through the handle members. The flexible member or the first handle member are configured to anchor the flexible member in a first handle member. This can either be accomplished by configuring the flexible member with an enlarged portion on one end or by configuring the flexible member in concert with the first handle member to anchor the elongate flexible member within an expanded region of the first handle member. The handle members can be configured for the construction of a hinged region that is easily hinged and unhinged. The surgical tool is assembled by extending the flexible member into the proximal end of a first handle member, passing it through an internal passageway of a first handle member, out the distal end of a first handle member and into the distal end of a second handle member, passing it through the second handle member and through the proximal end of a second handle member. Measurements are taken by extending the flexible member along the surface to be measured and noting the marking on the flexible member that intersects with the proximal end of said second handle member.

Provided herein are heteromultimer constructs with reduced or silenced effector function. In an embodiment is provided a heteromultimer construct comprising an IgG Fc construct having a first and a second Fc polypeptide, each Fc polypeptide comprising a modified lower hinge region wherein: the modified lower hinge region of said first Fc polypeptide comprises at least one amino acid modification, the modified lower hinge region of said second Fc polypeptide comprises at least one amino acid modification which is different from at least one amino acid modification of said first Fc polypeptide, and the IgG Fc construct displays reduced binding to all Fcγ receptors and to C1q protein as compared to a corresponding parent IgG Fc construct. Also provided are methods of producing such heteromultimer constructs, and methods of reducing ADCC for an antibody construct by reducing effector function.

The invention provides a surgical fastener. The fastener has a first element defining an axis of the fastener, and or more prongs attached to the first element at hinge regions. Deploying the fastener involves bending the prongs at the hinges so as to increase the distance of the prong tips from the axis and locking the fastener in this deployed configuration. The invention also provides a surgical fastening device and a method for attaching a surgical fastener to a site of a body tissue.

Provided are methods of generating chimeric antigen receptors (CAR). In some embodiments, library screening of CAR is performed by generating a vector encoding the CAR from random attachment of vectors from libraries of vectors encoding antigen-binding domains (e.g., scFv regions), hinge regions, and endodomains. In some embodiments, the vectors contain a transposon.

A non-detachable pull tab for a beverage container has a nose end, a lift end opposite the nose end, and a central webbing of a metallic material between the nose and lift end. The central webbing has a hinge region, a rivet island surrounding a rivet hole, a void region at least partially surrounding the rivet island, and a grab portion between the first void region and the lift end. The grab portion has an upper surface, a lower surface, and an aperture therethrough. The aperture is defined by a circumferential wall of the grab portion extending from the upper surface to the lower surface and includes a first segment of a reworked portion of a burr.