126 results about "Immunoglobulin heavy chain" patented technology

A bispecific antibody format providing ease of isolation is provided, comprising immunoglobulin heavy chain variable domains that are differentially modified in the CH3 domain, wherein the differential modifications are non-immunogenic or substantially non-immunogenic with respect to the CH3 modifications, and at least one of the modifications results in a differential affinity for the bispecific antibody for an affinity reagent such as Protein A, and the bispecific antibody is isolable from a disrupted cell, from medium, or from a mixture of antibodies based on its affinity for Protein A.

The present invention relates to a high efficiency method of expressing multispecific antibodies in eukaryotic cells. The invention is further drawn to a method of producing immunoglobulin heavy and light chain libraries, particularly using the trimolecular recombination method, for expression in eukaryotic cells. The invention further provides methods of selecting and screening for multispecific antibodies, and antigen-binding fragments thereof. The invention also provides kits for producing, screening and selecting multispecific antibodies. Finally, the invention provides multispecific antibodies, and antigen-binding fragments thereof, produced by the methods provided herein.

A significantly increased amount of a monoclonal antibody is obtained from the culture medium of recombinant hybridoma prepared by introducing genes encoding a protein identical to the immunoglobulin heavy chain polypeptide of the specific monoclonal antibody into an immortalized B cell (hybridoma) producing the monoclonal antibody.

The present invention relates to monovalent antibody, methods of making thereof and therapeutic uses thereof. In particular, the present invention provides a heterodimeric polypeptide comprising an immunoglobulin heavy chain and a fusion protein comprising an immunoglobulin light chain and an Fc molecule.

Disclosed herein are methods and compositions for enhancing the immunogenicity of a preselected protein or peptide antigen in a mammal. Immunogenicity is enhanced by fusing the preselected antigen to an immunoglobulin heavy chain constant region to produce an Fc-antigen fusion protein. The Fc-antigen fusion proteins bind Fc receptors on the surface of antigen presenting cells, thereby targeting the antigen to the antigen presenting cells in the mammal. In addition, disclosed is a family of adjuvants, for example, an Fc-adjuvant fusion protein, for use in combination with the Fc-antigen fusion proteins to enhance or modulate a particular immune response against the preselected antigen.

The present invention provides heterodimer pairs comprising a first heterodimer and a second heterodimer wherein each heterodimer comprises an immunoglobulin heavy chain or fragment thereof and an immunoglobulin light chain. At least one of the heterodimers comprises amino acid modifications in the C_H1 and/or C_L domains, amino acid modifications in the V_H and/or V_L domains or a combination thereof. The modified amino acid residues are part of the interface between the light chain and heavy chain and are modified in order to create preferential pairing between each heavy chain and a desired light chain such that when the two heavy chains and two light chains of the heterodimer pair are co-expressed in a mammalian cell, the heavy chain of the first heterodimer preferentially pairs with one of the light chains rather than the other. Likewise, the heavy chain of the second heterodimer preferentially pairs with the second light chain rather than first.

The invention is directed to methods of monitoring B-cell lymphoid proliferative disorders, such as B-cell acute lymphoblastic leukemias, by measuring the presence, absence and/or levels of correlating, or index, clonotypes and related clonotypes that have evolved therefrom, for example, as part of the disease condition. In one aspect, such methods are implemented by generating sequencing-based clonotype profiles and determining frequencies of correlating, or index, clonotypes present, including new clonotypes that have evolved therefrom, particularly, in the case of B-cell ALL, by VH substitution. The invention also includes use of such monitoring information to modify treatment status of a patient.

The present invention relates to a high efficiency method of expressing immunoglobulin molecules in eukaryotic cells. The invention is further drawn to a method of producing immunoglobulin heavy and light chain libraries, particularly using the trimolecular recombination method, for expression in eukaryotic cells. The invention further provides methods of selecting and screening for antigen-specific immunoglobulin molecules, and antigen-specific fragments thereof. The invention also provides kits for producing, screening and selecting antigen-specific immunoglobulin molecules. Finally, the invention provides immunoglobulin molecules, and antigen-specific fragments thereof, produced by the methods provided herein.

Provided herein are isolated heteromultimers comprising: at least one single domain antigen-binding construct attached to at least one monomer of a heterodimer Fc region; wherein the heterodimer Fc region comprises a variant CH3 domain comprising amino acid mutations that promote the formation of said heterodimer with stability comparable to that of a native Fc homodimer; and wherein said isolated heteromultimer is devoid of immunoglobulin light chains and optionally devoid of immunoglobulin CH1 region. These novel molecules comprise complexes of heterogeneous components designed to alter the natural way antibodies behave and that find use in therapeutics.

Disclosed are useful constructs and methods for the expression of proteins using primary translation products that are processed within a recombinant host cell. Constructs comprising a single open reading frame (sORF) are described for protein expression including expression of multiple polypeptides. A primary translation product (a pro-protein or a polyprotein) contains polypeptides such as inteins or hedgehog family auto-processing domains, or variants thereof, inserted in frame between multiple protein subunits of interest. The primary product can also contain cleavage sequences such as other proteolytic cleavage or protease recognition sites, or signal peptides which contain recognition sequences for signal peptidases, separating at least two of the multiple protein subunits. The sequences of the inserted auto-processing polypeptides or cleavage sites can be manipulated to enhance the efficiency of expression of the separate multiple protein subunits. Also disclosed are independent aspects of conducting efficient expression, secretion, and/or multimeric assembly of proteins such as immunoglobulins. Where the polyprotein contains immunoglobulin heavy and light chain segments or fragments capable of antigen recognition, in an embodiment a selectable stoichiometric ratio is at least two copies of a light chain segment per heavy chain segment, with the result that the production of properly folded and assembled functional antibody is made. Modified signal peptides, including such from immunoglobulin light chains, are described.

A non-human mammal containing an endogenous lambda light chain gene locus, an endogenous kappa light chain gene locus and an endogenous heavy chain gene locus, each of which can re-arrange so that immunoglobulin heavy and light chain genes are formed and expressed in B-cells following antigen challenge but said loci have been mutated so that the ability to form functional immunoglobulin tetramers comprising re-arranged heavy and light chains produced from said mutated loci has been substantially reduced or eliminated.

The present invention relates to a high efficiency method of expressing immunoglobulin molecules in eukaryotic cells. The invention is further drawn to a method of producing immunoglobulin heavy and light chain libraries, particularly using the trimolecular recombination method, for expression in eukaryotic cells. The invention further provides methods of selecting and screening for antigen-specific immunoglobulin molecules, and antigen-specific fragments thereof. The invention also provides kits for producing, screening and selecting antigen-specific immunoglobulin molecules. Finally, the invention provides immunoglobulin molecules, and antigen-specific fragments thereof, produced by the methods provided herein.

According to the present invention, a heterodimer protein composition that is composed of a first polypeptide comprising an immunoglobulin heavy chain constant region and a second polypeptide comprising CL-Fc prepared by fusion of an immunoglobulin light chain constant region (CL) and Fc region, and also has a deletion or substitution of Cys residues involved in disulfide bonds between CL and CH1, a purification method of the protein composition thereof, a preparation method of the protein composition thereof, a DNA and a vector encoding the protein composition thereof are provided

The immunoglobulin heavy chain binding protein BiP(GRP78), or a fragment thereof, provides a reagent for indicating the presence of rheumatoid arthritis (RA). The protein used is a recombinant BiP(GRP78) having a defined sequence. A prognostic and/or diagnostic test for RA may be an ELISA or a Western Blot that utilizes the BiP(GRP78) protein or a fragment thereof. Also disclosed are a method of testing for RA using BiP(GRP78) or a cDNA sequence coding therefor. Further disclosed is a method of treating RA by the BiP(GRP78) protein or corresponding cDNA.

The invention provides isolated amino acid sequences comprising the framework regions of an immunoglobulin heavy chain or light chain polypeptide, wherein certain amino acid residues of the framework regions are replaced with different amino acid residues that confer increased thermostability in vitro or in vivo. The invention also provides an isolated amino acid sequence of the constant region of an immunoglobulin heavy chain polypeptide wherein certain amino acid residues of the constant region are replaced with different amino acid residues that confer increased thermostability in vitro or in vivo.

The present invention concerns an antibody or fragment thereof, capable of binding to CD 160, said antibody comprising a) a light chain comprising three light chain complementary regions (CDRs) having the following amino acid sequences: (i) the light chain CDR1: QSISNH (SEQ ID NO: 1), (ii) the light chain CDR2: YAS, (iii) the light chain CDR3: QQSNSWPLT (SEQ ID NO: 2), and a light chain framework sequence from an immunoglobulin light chain; and b) a heavy chain comprising three heavy chain complementary regions (CDRs) having the following amino acid sequences: (i) the heavy chain CDR1: GYTFTDYW (SEQ ID NO: 3), (ii) the heavy chain CDR2: IYPGDDDA (SEQ ID NO: 4); (iii) the heavy chain CDR3: ARRGIAAVVGGFDY (SEQ ID NO: 5); and a heavy chain framework sequence from an immunoglobulin heavy chain; a pharmaceutical comprising said antibody and the use of said antibody for preparation of a medicament for treating and/or preventing a pathology associated with endothelial cells proliferation engaged in an angiogenesis process.