1641 results about "Disulfide bond" patented technology

The invention relates to a method of preparing heteromultimeric polypeptides such as bispecific antibodies, bispecific immunoadhesins and antibody-immunoadhesin chimeras. The invention also relates to the heteromultimers prepared using the method. Generally, the method provides a multispecific antibody having a common light chain associated with each heteromeric polypeptide having an antibody binding domain. Additionally the method futher involves introducing into the multispecific antibody a specific and complementary interaction at the interface of a first polypeptide and the interface of a second polypeptide, so as to promote heteromultimer formation and hinder homomultimer formation; and/or a free thiol-containing residue at the interface of a first polypeptide and a corresponding free thiol-containing residue in the interface of a second polypeptide, such that a non-naturally occurring disulfide bond is formed between the first and second polypeptide. The method allows for the enhanced formation of the desired heteromultimer relative to undesired heteromultimers and homomultimers.

The present invention discloses a one-step process for the production of cytotoxic conjugates of maytansinoids and cell binding agents. Maytansinoids having a disulfide linker that bears a reactive moiety are linked to cell binding agents, such as antibodies, without prior modification of the cell binding agent. These conjugates are useful as therapeutic agents which are delivered specifically to target cells and are cytotoxic.

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.

Disclosed is a composition of matter of the formula

(X¹)_a—(F¹)_d—(X²)_b—(F²)_e—(X³)_c  (I)

and multimers thereof, in which F¹ and F² are half-life extending moieties, and d and e are each independently 0 or 1, provided that at least one of d and e is 1; X¹, X², and X³ are each independently -(L)_f-P-(L)_g-, and f and g are each independently 0 or 1; P is a toxin peptide of no more than about 80 amino acid residues in length, comprising at least two intrapeptide disulfide bonds; L is an optional linker; and a, b, and c are each independently 0 or 1, provided that at least one of a, b and c is 1. Linkage to the half-life extending moiety or moieties increases the in vivo half-life of the toxin peptide, which otherwise would be quickly degraded. A pharmaceutical composition comprises the composition and a pharmaceutically acceptable carrier. Also disclosed are a DNA encoding the inventive composition of matter, an expression vector comprising the DNA, and a host cell comprising the expression vector. Methods of treating an autoimmune disorder, such as, but not limited to, multiple sclerosis, type 1 diabetes, psoriasis, inflammatory bowel disease, contact-mediated dermatitis, rheumatoid arthritis, psoriatic arthritis, asthma, allergy, restinosis, systemic sclerosis, fibrosis, scleroderma, glomerulonephritis, Sjogren syndrome, inflammatory bone resorption, transplant rejection, graft-versus-host disease, and lupus and of preventing or mitigating a relapse of a symptom of multiple sclerosis are also disclosed.

The present invention relates to a novel method for the production of short chain polypeptides, including polypeptides having up to 3 disulfide bonds and/or structures rich in basic amino acid residues, and open structured short chain polypeptides, e.g. glucagon, glucagon like peptides and their functional analogues, in genetically modified yeast cells, said genetically modified yeast cells, and a method for the preparation of said yeast cells.

Bioscaffoldings formed of hydrogels that are crosslinked in situ in an infarcted region of the heart (myocardium) by a Michael's addition reaction or by a disulfide bond formed by an oxidative process are described. Each of the bioscaffoldings described includes hyaluronan as one of the hydrogel components and the other component is selected from collagen, collagen-laminin, poly-l-lysine, and fibrin. The bioscaffolding may further include an alginate component. The bioscaffoldings may have biofunctional groups such as angiogenic factors and stem cell homing factors bound to the collagen, collagen-laminin, poly-l-lysine, or fibrinogen hydrogel component. In particular, the biofunctional groups may be PR11, PR39, VEGF, bFGF, a polyarginine/DNA plasmid complex, or a DNA/polyethyleneimine (PEI) complex. Additionally, the hydrogel components may be injected into the infarct region along with stem cells and microspheres containing stem cell homing factors. The bioscaffolding may be formed on a stent or a cardiac medical device.

Compositions, kits, and methods for rebuilding the disulfide bonds in hair that is damaged due to a hair coloring treatment are disclosed. The compositions contain one or more compounds that covalently crosslink at least two thiol groups in the hair. The compositions may be applied subsequent to a hair coloring treatment or simultaneously with a hair coloring treatment. Under normal hair washing conditions, the covalent crosslinks formed are not succeptable to reduction or hydrolysis. Use of the crosslinking compositions prevent the reversion of the hair's disulfide bonds to its reduced state, for at least one week, preferably at least three months, more preferably at least one year, most preferably at least greater than one year, after at least one application of the composition.

Dithioamine reducing agents useful for the reduction of disulfide bonds. The reducing agents of this invention are useful, for example, to reduce disulfide bonds, particularly in proteins, or to prevent the formation of disulfide bonds, particularly in proteins and other biological molecules. Reducing agents of this invention are useful and suitable for application in a variety of biological applications, particularly as research and synthetic reagents. The invention provides S-acylated dithioamines which can be selectively activated reducing agents by removal of the S-acyl groups enzymatically or chemically. The invention further provides dithiane precursors of thioamino reducing agents. The invention provides dithioamine reducing agents, S-acylated dithioamines and dithianes which are immobilized on surfaces, including among others, glass, quartz, microparticles, nanoparticles and resins.

Novel lipid compounds are provided that may be termed "pro-cationic" in that they are neutral or negatively charged until they are either brought into contact with cellular membranes or are internalized by cells. The lipids have a hydrophobic tail group and a hydrophilic head group, the head group incorporating both a positively and negatively charged region at physiological pH. The hydrophobic tail group is stably connected to the positive region of the head group which in turn is connected to the negative region by a disulfide bond that is susceptible to cleavage by membrane-bound and intracellular factors. Cleavage of the disulfide bond removes the negatively charged region from the head group resulting in a lipid that is cationic and therefor fusogenic with negatively charged cell membranes. Consequently, lipids of the invention are useful as components of liposomes that serve as vehicles for delivering pharmaceutical agents into cells with reduced toxicity.

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.

A process for producing non-woven silk fiber fabrics comprises the following steps: a) obtaining silk fibroin, for example either from silk cocoons, or silk textiles or waste silk; b) removing the sericin layer covering the silk fibroin fibers, when present; c) breaking the disulfide bonds between heavy (350 kDa) and light (27 kDa) chains of silk fibroin in order to obtain the production of chain fragments which serve as a specific cellular recognition sites promoting the attachment and growth of cells, d) homogenising of the material resulting from step c).

A method of forming solid gluten-based pet chew is provided wherein a gluten mixture is heated to a maximum temperature of up to about 80° C. to create a substantially homogeneous and flowable mixture under extrusion processing conditions. The formulation includes from about 40-90% by weight of grain protein, from about 10-40% by weight plasticizer, and at least about 0.01 by weight of a reducing agent such as sodium bisulfite for cleaving disulfide bonds present in the grain protein. Dental health agents including an acidulent and a chelator are added to promote good dental health. Optional ingredients such as fillers, fiber, lubricant/mold release agents and colorants can also be used. The formulations can be processed in extrusion or injection molding equipment.

A conjugate between a target-seeking moiety and a modified superantigen, characterized in that the superantigen is a wild-type superantigen (SA I) in which an amino acid residue in a superantigen region (region I) determining binding to TCR, preferably TCRVβ, and T cell activation have been replaced by another amino acid residue while retaining the ability to activate a subset of T cells.

In preferred embodiment the modified superantigen is a chimer between at least two wild-type superantigens (SA I, SA II etc) characterized in that one or more amino acid residues in a region determining binding to TCR and T cell activation have been interchanged between various wild-type superantigens.

A therapeutic method making use of modified/chimeric superantigens as defined in the preceding paragraphs.

An antibody preparation in which the cysteine residues that provide for interchain disulfide bonds have been mutated so as to forbid interchain disulfide bridges, preferably to serine residues, for use as pharmaceutical.

The invention relates to self-healing polyurethane resin containing disulfide bond and a preparation method thereof. The polyurethane resin comprises, by weight parts, 10-30 parts of polyether or polyester polyol, 3-20 parts of polyisocyanates, 1-10 parts of chain extender containing the disulfide bond, 0.001-1 part of organic tin or tertiary amine catalyst and 50-80 parts of organic solvent. The method for preparing the self-healing polyurethane resin containing the disulfide bond comprises the steps of weighing raw materials, stirring, heating and performing dehydration for the polyether or polyester polyol under vacuum conditions, lowering the temperature to 85 DEG C or below, adding the polyisocyanates and the organic tin or tertiary amine catalyst, reacting, lowering the temperature to 50 DEG C or below, adding the organic solvent and the chain extender containing the disulfide bond, reacting and performing vacuum defoamation to obtain the self-healing polyurethane resin. The self-healing polyurethane resin heals by itself under the heating or ultraviolet (UV) light conditions, the required conditions are mild, the healing speed is high, the effect is good, the preparation method is simple and easy to control, and raw materials are goods of commercialized production and are cheap and easy to obtain.

The present invention relates to a self-molding permanent agent and a method for proceeding free-rod and free-band type permanent, more particularly to a self-molding permanent agent comprising (a) a reducing composition containing a reducing agent reducing a disulfide bond of cystine on the hair and a molding stimulant spontaneously molding to fix a hair design; (b) a molding composition inducing to mold after reacting with the molding stimulant; and (c) a softening composition releasing the action of a molding stimulant, and a method for pressing a free-rod and free-band type permanent, which overcomes a disadvantage in the conventional method for pressing a permanent that needs to wear a curling device such as rods for a permanent (perm rod) or rubber band and improves to apply a wave set without a hair-curling device for a short time, since it has a self-molding feature.

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.

A hydratable, highly absorbent keratin solid fiber or powder capable of absorbing a large weight excess of water may be produced by partially oxidizing hair keratin disulfide bonds to sulfonic acid residues and reacting the sulfonic acid residues with a cation. The neutralized suspension can be filtered, washed, and dried, leaving keratin solid which can be shredded into fibers and further ground into powder. Addition of water to the solid produces a hydrogel. The powder or hydrogel may be useful as an absorbent material, as a therapeutic for skin, or as an excipient. The keratin materials can be incorporated into nonwoven films. Another use for the hydrogel is as a biocompatible viscoelastic filler for implant applications.

Pharmaceutical, chemical and biological agents containing a reversible disulfide linker are described. These agents can also be covalently bound or contained in delivery vehicles for delivering the agents to desired targets or areas. Also described are delivery vehicles which contain an agent having a reversible disulfide linker and to vehicles that are covalently linked to the agent containing a reversible disulfide linker. The modifications described herein can modify properties of the agents and vehicles, thereby providing desired solubility, stability, hydrophobicity and targeting while the reversibility of the linker can leave the agent to which it is attached free from residual chemical groups after being reduced.