82 results about "Multimerin" patented technology

Methods are provided for the synthesis and secretion of recombinant proteins preferably large mammalian proteins or hetero-multimeric proteins at high levels and for prolonged time in polyploid, preferably diploid yeast. These methods use various mating competent yeast, including Pichia. In a preferred embodiment, a first expression vector is transformed into a first haploid cell; and a second expression vector is transformed into a second haploid cell. The transformed haploid cells, each individually synthesizing a non-identical polypeptide, are identified and then genetically crossed or fused. The resulting diploid strains are utilized to produce and secrete fully assembled and biologically functional hetero-multimeric protein.

Described herein are methods for the efficient production of antibodies and other multimeric protein complexes (collectively referred to herein as heteromultimeric proteins) capable of specifically binding to more than one target. The targets may be, for example, different epitopes on a single molecule or located on different molecules. The methods combine efficient, high gene expression level, appropriate assembly, and ease of purification for the heteromultimeric proteins. The invention also provides methods of using these heteromultimeric proteins, and compositions, kits and articles of manufacture comprising these antibodies.

Described herein are Fc variants and methods for the efficient production of antibodies and other multimeric protein complexes (collectively referred to herein as heteromultimeric proteins). Heteromultimeric proteins may be capable of specifically binding to more than one target. The targets may be, for example, different epitopes on a single molecule or located on different molecules. The methods combine efficient, high gene expression level, appropriate assembly, and ease of purification for the heteromultimeric proteins. The invention also provides methods of using these heteromultimeric proteins, and compositions, kits and articles of manufacture comprising these antibodies.

The invention provides engineered heteromultimeric protein complexes constructed using one, two, or three tethers and methods for making, using, and purifying such complexes, such as antibodies with different binding properties.

Described herein are methods for the efficient production of antibodies and other multimeric protein complexes (collectively referred to herein as heteromultimeric proteins) capable of specifically binding to more than one target. The targets may be, for example, different epitopes on a single molecule or located on different molecules. The methods combine efficient, high gene expression level, appropriate assembly, and ease of purification for the heteromultimeric proteins. The invention also provides methods of using these heteromultimeric proteins, and compositions, kits and articles of manufacture comprising these antibodies.

The present invention relates to molecules preferably of polypeptide nature with negative regulatory activity on the amount or activity of TGF-β through direct interaction with pro-TGF-β, and containing as active region a cysteine-rich polypeptide sequence defined as “EMI domain”, or its subfragments, wherein said “EMI domain” has at least 25% sequence homology to the ID NO2 sequence for pharmaceutical use. Even more preferably said polypeptide sequence consists of the EMI domain of the following proteins: emilin-1, emilin-2 and / or multimerin-2 or their subfragments having a length of at least 6 amino acids, capable of inhibiting the conversion of pro-TGFβ to mature TGFβ as anti-hypertensive drugs and polypeptides active on the cardiovascular system. The invention extends to the use of molecules which are known to negatively regulate TGF-β and to molecules which interfere with TGF-β binding to its receptors, or to inhibitors of TGF-β mRNA synthesis or TGF-β expression for the same therapeutic uses as anti-hypertensive drugs and polypeptides active on the cardiovascular system.

Methods are provided for the synthesis and secretion of recombinant hetero-multimeric proteins in mating competent yeast. A first expression vector is transformed into a first haploid cell; and a second expression vector is transformed into a second haploid cell. The transformed haploid cells, each individually synthesizing a non-identical polypeptide, are identified and then genetically crossed or fused. The resulting diploid strains are utilized to produce and secrete fully assembled and biologically functional hetero-multimeric protein.

The invention relates to semi-synthetic biologic molecules which are conjugates of GLP-1 peptides and human multimeric proteins or protein fragments, such as an antibody Fc joined by a non-peptidyl bond. The constructs demonstrate biological activity and are useful making therapeutic compositions and therapeutic formulations for use in treating diseases characterized by lack of glycemic control.

Provided herein are multifunctional heteromultimer proteins. In specific embodiments is a heteromultimer comprising: at least two polypeptide constructs, each polypeptide construct comprising at least one cargo polypeptide attached to a transporter polypeptide, said transporter polypeptides derived from a monomeric native protein such that said monomeric constructs associate to form the heteromultimer and said transporter polypeptides associate to form a quasi-native structure of the monomeric native protein or analog thereof. These therapeutically novel molecules encompass heteromultimers comprising constructs that function as scaffolds for the conjugation or fusion of therapeutic molecular entities (cargo polypeptides) resulting in the creation of bispecific or multivalent molecular species. Provided herein is a method for creation of bispecific or multivalent molecular species.

The present invention refers to novel hetero-multimeric proteins obtained from modified ubiquitin capable of binding the extradomain B of fibronectin (ED-B) with high affinity. Furthermore, the invention refers to fusion proteins comprising said recombinant protein fused to a pharmaceutically and / or diagnostically active component. The invention is further directed to the use of said proteins in medical treatment methods.

A composition having an agent adapted to affect a multimeric protein by binding to a binding site of the multimeric protein and thereby affecting an equilibrium of units, wherein the multimeric protein has an assembly having a plurality of said units, wherein each of the units has a first complementary surface and a second complementary surface and wherein the first complementary surface of one unit is associated with the second complementary surface of another unit, provided that the assembly is at least one of different quaternary isoforms on a condition that in the multimeric protein (1) a structure of each of the units determines a structure of the different quaternary isoforms, (2) the units are in the equilibrium and (3) the structure of the different quaternary isoforms influences a function of the multimeric protein.

A composition having an agent adapted to affect a multimeric protein by binding to a binding site of the multimeric protein and thereby affecting an equilibrium of units, wherein the multimeric protein has an assembly having a plurality of said units, wherein each of the units has a first complementary surface and a second complementary surface and wherein the first complementary surface of one unit is associated with the second complementary surface of another unit, provided that the assembly is at least one of different quaternary isoforms on a condition that in the multimeric protein (1) a structure of each of the units determines a structure of the different quaternary isoforms, (2) the units are in the equilibrium and (3) the structure of the different quaternary isoforms influences a function of the multimeric protein.

Multimeric protein structures comprising at least two alpha-galactosidase monomers being covalently linked to one another via a linking moiety are disclosed herein, as well a process for preparing same, and methods of treating Fabry disease via administration of a multimeric protein structure. The disclosed multimeric protein structures exhibit an improved performance, in terms of enhanced activity and / or a longer lasting activity under both lysosomal conditions and in a serum environment.

This invention relates to the PrtR-PrtK cell surface protein of Porphyromonas gingivalis and in particular a multimeric cell association protein complex comprising the PrtR and PrtK proteins. Accordingly the invention provides a substantially purified antigenic complex for use in raising an antibody response directed against Porphyromonas gingivalis. The complex comprises at least one multimeric protein complex of arginine-specific and lysine-specific thiol endopeptidases each containing at least one adhesin domain, the complex having a molecular weight of greater than about 200 kDa. The invention also relates to pharmaceutical compositions and associated agents based on said complex for the detection, prevention and treatment of Periodontal disease associated with P. gingivalis.

An objective of the invention is to provide a drug delivery vehicle capable of allowing a vaccine or adjuvant to reach a target cell or tissue efficiently while being capable of improving the immunogenicity of the vaccine or capable of enhancing the immunostimulating effect of the adjuvant as well as a vaccine or adjuvant utilizing the same. Said drug delivery vehicle contains a multimeric protein having a coiled coil structure and a ligand molecule to a receptor of an immune cell.

The present invention relatas to novel immunogenic variants of multimeric proteins such as immunogenic variants of interleukin 5 (IL5) and tumour necrosis factor alpha (TNF, TNFalpha). The variants are, besides from being immunogenic in the autologous host, also highly similar to the native 3D structure of the proteins from which they are derived. Certain variants are monomeric mimics of the multimers, where peptide linkers (inert or T helper epitope containing) ensure a spatial organisation of the monomomer units that facilitate correct folding. A subset of variants are monomer TNFalpha variants that exhibit a superior capability of assembling into multimers with a high structural similarity to the native protein. Also disclosed are methods of treatment and production of the variants as well as DNA fragments, vectors, and host cells.

A method is disclosed for forming multimeric proteins. The method relies on intermolecular trans-splicing of a split intein either in vivo or in vitro.

The invention relates to a transcriptionally active recombinant linear polynucleotide encoding a multimeric protein comprising in the following order, a first promoter sequence, a first encoding polynucleotide sequence, a bidirectional regulatory sequence, a second encoding polynucleotide sequence and a second promoter sequence, wherein the first and second encoding polynucleotide sequences are in convergent transcriptional orientation, each encoding polynucleotide sequence encodes a component of the multimeric protein and the bidirectional regulatory sequence is operably linked to the first and second encoding polynucleotide sequences and the multimeric protein is an antibody or fragment thereof and each encoding polynucleotide sequence encodes one or more antibody domains or fragments thereof.

The present invention discloses improved methods for preparing multimeric protein complexes, such as redoxins and immunoglobulins, associated with oil bodies. The redoxin is enzymatically active when prepared in combination with oil bodies. The invention also provides related nucleic acids, proteins, cells, plants and compositions.

This invention relates to the PrtR-PrtK cell surface protein of Porphyromonas gingivalis and in particular a multimeric cell association protein complex comprising the PrtR and PrtK proteins. Accordingly the invention provides a substantially purified antigenic complex for use in raising an antibody response directed against Porphyromonas gingivalis. The complex comprises at least one multimeric protein complex of arginine-specific and lysine-specific thiol endopeptidases each containing at least one adhesin domain, the complex having a molecular weight of greater than about 200 kDa. The invention also relates to pharmaceutical compositions and associated agents based on said complex for the detection, prevention and treatment of Periodontal disease associated with P. gingivalis.

The present invention relatas to novel immunogenic variants of multimeric proteins such as immunogenic variants of interleukin 5 (IL5) and tumour necrosis factor alpha (TNF, TNFalpha). The variants are, besides from being immunogenic in the autologous host, also highly similar to the native 3D structure of the proteins from which they are derived. Certain variants are monomeric mimics of the multimers, where peptide linkers (inert or T helper epitope containing) ensure a spatial organisation of the monomomer units that facilitate correct folding. A subset of variants are monomer TNFalpha variants that exhibit a superior capability of assembling into multimers with a high structural similarity to the native protein. Also disclosed are methods of treatment and production of the variants as well as DNA fragments, vectors, and host cells.

The present invention provides compositions comprising modified bacterial toxins and methods for using the modified bacterial toxins for targeting particular cell populations and for treating diseases.

A soluble multimeric protein or polypeptide is disclosed that is able to inhibit interaction of leukocyte Fcgamma receptors (FcgammaR) and immunoglobulin G (IgG). The protein or polypeptide comprises two or more linked Fc binding regions, at least one of which is derived from an FcgammaR type receptor and, particularly, FcgammaRIIa. Also described are polynucleotide molecules encoding the protein or polypeptide and the use thereof in methods of treating a subject for an immune-complex (IC)-mediated inflammatory disease.

Described herein are methods for the efficient production of a heteromultimeric protein, such as a bispecific antibody. Heteromultimeric proteins may be capable of specifically binding more than one target molecule or different epitopes on a single target molecule. The methods modulate parameters to improve assembly of the heteromultimeric proteins at higher yield and efficiency than otherwise possible. Also described are compositions comprising a hinge-containing polypeptide, such as a half-antibody.

A recombinant heteromultimeric protein including at least (a) a polypeptide fusion molecule A consisting of a C4BP α-chain C-terminal fragment and a polypeptide fragment heterologous to said α-chain, and (a) a polypeptide fusion molecule B consisting of a C4BP β-chain C-terminal fragment and a polypeptide fragment heterologous to said β-chain, wherein (a) and (b) are linked in the C-terminal portion to form said multimeric protein.

The invention described herein encompasses (1) artificial preproproteins and the polynucleotides encoding them, (2) methods for producing these biomolecules, and (3) methods for their use. The artificial preproproteins of this invention comprise a protein assembly capable of producing a multimeric protein from a single protein. FIG. 4 illustrates generally the process by which a polynucleotide encoding the artificial preproprotein is introduced into a cell and a biomolecule of interest is produced.

Methods are provided for intein mediated trans-splicing of immobilized polypeptides and for producing cyclic polypeptides in vivo or in vitro.

The present invention relates to expression and assembly of foreign multimeric proteins—e.g., antibodies—in plants, as well as to transgenic plants that express such proteins. In one of several preferred embodiments, the generation and assembly of functional secretory antibodies in plants is disclosed. The invention also discloses compositions produced by the transgenic plants of the present invention and methods of using same.