67 results about "Monobody" patented technology

The invention provides immunoglobulin polypeptides comprising variant amino acids in CDRs of antibody variable domains. In one embodiment, the polypeptide is a variable domain of a monobody and has a variant CDRH3 region. These polypeptides provide a source of great sequence diversity that can be used as a source for identifying novel antigen binding polypeptides. The invention also provides these polypeptides as fusion polypeptides to heterologous polypeptides such as at least a portion of phage or viral coat proteins, tags and linkers. Libraries comprising a plurality of these polypeptides are also provided. In addition, methods of and compositions for generating and using these polypeptides and libraries are provided.

The invention provides polypeptides comprising a variant heavy chain variable framework domain (VFR). In some embodiments, the amino acids defining the VFR form a loop of an antigen binding pocket. In an embodiment, the polypeptide is a variable domain of a monobody and has a variant VFR. The polypeptide may optionally comprise one or more complementary determining regions (CDRs) of antibody variable domains. In an embodiment, the polypeptide is a variable domain of a monobody and has a variant VFR and one or more variant CDRs. Libraries of polypeptides that include a plurality of different antibody variable domains generated by creating diversity in a VFR, and optionally, one or more CDRs are provided and may be used as a source for identifying novel antigen binding polypeptides that can be used therapeutically or as reagents. The invention also provides fusion polypeptides, compositions, and methods for generating and using the polypeptides and libraries.

The invention provides polypeptides comprising a variant heavy chain variable framework domain (VFR). In some embodiments, the amino acids defining the VFR form a loop of an antigen binding pocket. In an embodiment, the polypeptide is a variable domain of a monobody and has a variant VFR. The polypeptide may optionally comprise one or more complementary determining regions (CDRs) of antibody variable domains. In an embodiment, the polypeptide is a variable domain of a monobody and has a variant VFR and one or more variant CDRs. Libraries of polypeptides that include a plurality of different antibody variable domains generated by creating diversity in a VFR, and optionally, one or more CDRs are provided and may be used as a source for identifying novel antigen binding polypeptides that can be used therapeutically or as reagents. The invention also provides fusion polypeptides, compositions, and methods for generating and using the polypeptides and libraries.

The present invention provides a technique for specific assembly of monomeric polypeptides to form a heteromultimer. This technique is particularly useful for generating a genetically diverse repertoire of heteromultimers such as antigen-binding units. The invention also provides both non-single-chain and single-chain antigen-binding units that are assembled by the technique described herein. The present invention also provides recombinant polynucleotides, vectors, host cells, and kits for producing the subject antigen-binding units. Further provided by the invention are methods of using the subject antigen-binding units.

A method of identifying a polypeptide monobody having target protein binding activity, said method comprising: providing a host cell comprising (i) a reporter gene under control of a 5′ regulatory region operable in the host cell, (ii) a first chimeric gene which encodes a first fusion polypeptide comprising a target protein, or fragment thereof, fused to a C-terminus of a DNA-binding domain which binds to the 5′ regulatory region of the reporter gene, and (iii) a second chimeric gene which encodes a second fusion polypeptide comprising a polypeptide monobody fused to a transcriptional activation domain; and detecting expression of the reporter gene, which indicates binding of the polypeptide monobody of the second fusion polypeptide to the target protein such that the transcriptional activation domain of the second fusion polypeptide is in sufficient proximity to the DNA-binding domain of the first fusion polypeptide to allow expression of the reporter gene.

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.

Featured are DNA molecules, expression vectors, and host cells useful for creation of immunoglobulins, as well as novel immunoglobulin molecules termed monobodies. Additionally provided are methods of production of immunoglobulins, including monobodies, as well as methods of using the disclosed immunoglobulin and monobody constructs, expression vectors and host cells containing DNA encoding molecules for production of immunoglobulin and monobody proteins.

The present invention provides a fibronectin type III (Fn3) molecule, wherein the Fn3 contains a stabilizing mutation. The present invention also provides Fn3 polypeptide monobodies, nucleic acid molecules encoding monobodies, and variegated nucleic acid libraries encoding such monobodies. Also provided are methods of preparing a Fn3 polypeptide monobody, and kits to perform the methods.

The invention discloses bispecific recombinant protein. The bispecific recombinant protein comprises a high-affinity tumor-targeted arm and a low-affinity fusion protein for blocking interaction of CD47 and SIRPalpha, wherein an antibody corresponding to the high-affinity tumor-targeted arm is not combined with the CD47, and the bonding affinity to target antigens on tumor cells is at least 6 times of the bonding affinity of the monomeric fusion protein and dimer corresponding to the low-affinity fusion protein for blocking the interaction of the CD47 and the SIRPalpha to the CD47 on the tumorcells; the low-affinity fusion protein for blocking mutual action of the CD47 and SIRPalpha contains SIRPalpha extracellular truncation. The invention also discloses a nucleic-acid molecule for encoding the recombinant protein and application of the recombinant protein and the nucleic-acid molecule in preparation of medicines for treating tumors. The bispecific recombinant protein disclosed by the invention has the beneficial effects that the bonding abundance of tumor targeting saturation of the recombinant protein with the function of adjusting macrophage is obviously improved by the bispecific recombinant protein, the side effect of the non-tumor targeting is reduced and the application value is large clinically.

A system for expressing antigenic polypeptides in oligomeric form fuses the antigenic polypeptide to an oligomerisation polypeptide such that the oligomerisation polypeptide can interact with other oligomerisation polypeptides and bring multiple copies of the antigenic polypeptide into close proximity in the form of an oligomer. Expressing the polypeptides in oligomeric form in this way can improve their immunogenicity compared to a monomeric form.

The present invention provides novel, single chain Fc fusion proteins having improved properties. The invention provides single chain fusions of soluble proteins fused to the Fc region of an immunoglobulin via a novel linker comprising a constant region of an immunoglobulin light chain linked to a CH1 constant region of an immunoglobulin heavy chain. This novel linker confers favorable properties on the Fc fusion proteins of the invention such as improved bioactivity and increased half-life as compared to non-Fc fusion counterparts or as compared to prior art Fc fusion proteins. The novel Fc fusion protein scaffold as described herein may be designed to include soluble proteins of interest capable of binding or interacting with any target of interest. Preferably, the Fc fusion protein of the invention is a dimer. The dimer preferably forms via a disulfide bond between free cysteine residues in the hinge region of two monomeric Fc fusion proteins of the invention.

A fibronectin type III (Fn3) polypeptide monobody, a nucleic acid molecule encoding said monobody, and a variegated nucleic acid library encoding said monobody, are provided by the invention. Also provided are methods of preparing a Fn3 polypeptide monobody, and kits to perform said methods. Further provided is a method of identifying the amino acid sequence of a polypeptide molecule capable of binding to a specific binding partner (SBP) so as to form a polypeptide:SSP complex, and a method of identifying the amino acid sequence of a polypeptide molecule capable of catalyzing a chemical reaction with a catalyzed rate constant, kcat, and an uncatalyzed rate constant, kuncat, such that the ratio of kcat / kuncat, is greater than 10.

The present inventors successfully produced monoclonal antibodies that are specific to only soluble Aβ oligomers, but do not recognize soluble Aβ monomers, which are physiological molecules. It was demonstrated that the antibodies are useful as diagnostic / therapeutic monoclonal antibodies for Alzheimer's disease.

The present invention provides monoclonal antibodies that are specific for the Dengue non-structural glycoprotein NS1 in monomeric and / or oligomeric (primarily dimeric) form, together with methods, including ELISA and lateral flow assays, that employ the disclosed antibodies for the early detection of Dengue virus infection. Diagnostic kits for the detection of Dengue infection are also provided, such kits including the disclosed monoclonal and / or polyclonal antibodies.

The present invention provides, in particular embodiments, for modified recombinant T cell receptor (TCR) ligands (RTLs) comprising a MHC class I or MHC class II component. The modified RTLs have redesigned surface features that preclude or reduce aggregation, wherein the modified molecules retain the ability to bind Ag-peptides, target antigen-specific T cells, inhibit T cell proliferation in an Ag-specific manner and have utility to treat, inter alia, autoimmune disease and other conditions mediated by antigen-specific T cells in vivo.