16 results about "Immunoglobulin light chain" patented technology

A genetically modified mouse is provided, wherein the mouse expresses an immunoglobulin light chain repertoire characterized by a limited number of light chain variable domains. Mice are provided that present a choice of two human light chain variable gene segments such that the immunoglobulin light chains expresses by the mouse comprise one of the two human light chain variable gene segments. Methods for making bispecific antibodies having universal light chains using mice as described herein, including human light chain variable regions, are provided. Methods for making human variable regions suitable for use in multispecific binding proteins, e.g., bispecific antibodies, and host cells are provided.

To provide transgenic mammals expressing bovine-based immunoglobulins, including transgenic rodents expressing bovine-based immunoglobulins for the development of bovine therapeutic antibodies.SOLUTION: A transgenic rodent or rodent cell is provided comprising an engineered partially bovine immunoglobulin light chain locus comprising bovine immunoglobulin λ light chain variable region gene segments, wherein the engineered immunoglobulin locus is capable of expressing immunoglobulins comprising bovine variable domains, and wherein the transgenic rodent produces or is likely to produce more immunoglobulins comprising λ light chains than immunoglobulins comprising κ light chains.SELECTED DRAWING: Figure 13

The present invention relates to an antibody comprising an immunoglobulin heavy chain variable region (VH), an immunoglobulin light chain variable region (VL), an immunoglobulin light chain constant region (CL), an immunoglobulin heavy chain constant region (CH), and two sequences encoding peptide linkers (PL1 and PL2), wherein VH is fused to VL through PL1 and CL is fused to CH through PL2, and its uses for therapeutic or diagnostic purposes. The invention further relates to a recombinant nucleic acid molecule encoding said antibody, and an expression cassette, vector, viral particle, host cell, transgenic organism or pharmaceutical composition comprising said recombinant nucleic acid molecule.

The present disclosure is directed to antibodies or antigen-binding portions thereof that specifically bind free immunoglobulin light chains (FLC), polynucleotides and vectors encoding the same, and pharmaceutical compositions comprising the same. Some aspects of the disclosure are directed to methods of measuring FLC in a biological sample comprising contacting the sample with the anti-FLC antibody. Some aspects of the disclosure are directed to methods of treating a disease or condition comprising administering the anti-FLC antibody to a subject in need thereof.

Provided in the present invention are a genetically modified animal having a restricted humanized light chain immunoglobulin locus, a method for producing the animal, and a method for producing a common light chain antibody and an antibody library thereof using the animal. The restricted humanized light chain immunoglobulin locus comprises a portion of a V region and a portion of a J region from a light chain Kappa variable region locus of a human immunoglobulin.

Provided herein are anti-human λ light chain antibodies or human λ light chain binding antibody fragments that bind an epitope specific of the human λ light chain. Also provided are polynucleotides and vectors encoding the same, and compositions comprising anti-human λ light chain antibodies or human λ light chain binding antibody fragments. The anti-human λ light chain antibodies or human λ light chain binding antibody fragments are useful for measuring human λ light chain in a biological sample comprising contacting the sample with the anti-human λ light chain antibodies or human λ light chain binding antibody fragments. The anti-human λ light chain antibodies or human λ light chain binding antibody fragments are also useful for reducing λ light chain aggregates.

Provided herein are compounds that stabilize immunoglobulin light chains, and pharmaceutically acceptable derivatives thereof. Also provided are pharmaceutical compositions containing the compounds and methods of using the compounds for treating a subject with light chain amyloidosis.

Provided herein are compounds and pharmaceutically acceptable derivatives thereof for use in compositions and methods of treating light chain amyloidosis. Also provided are methods of degrading immunoglobulin light chains using the compounds and compositions provided herein.

The invention relates to the technical field of bioengineering, in particular to an immunoglobulin light chain mutant, nucleotide, a recombinant expression vector and application. Escherichia coli is used as a chassis for heterologous expression of bovine immunoglobulin IgG light chains, an IgG light chain mutant with significantly improved soluble expression in Escherichia coli is obtained by using error-prone PCR and high-throughput screening, and a corresponding mutant strain is further constructed based on the IgG light chain mutant; wherein the soluble B-LC content of the mutant strain 2-8 (in an immune globulin light chain, the second amino acid is mutated into threonine from alanine, the 34 amino acid is mutated into aspartic acid from glycine, the 57 amino acid is mutated into lysine from glutamine, the 101 amino acid is mutated into valine from glutamic acid, and the 209 amino acid is mutated into arginine from tryptophan) is 29.1 mg / L; and the expression is 1.86 times that of the control soluble expression.

Non-human animals (and / or non-human cells) and methods for using said non-human animals (and / or non-human cells) are provided, said non-human animals (and / or non-human cells) having a genome containing sequences encoding human antibodies (i.e., immunoglobulin genes). The non-human animals described herein express antibodies containing immunoglobulin (Ig) light chains, said immunoglobulin light chains being characterized by the presence of a human Vλ domain. In some embodiments, the non-human animals provided herein are characterized by expressing antibodies containing a human Vλ light chain encoded by a sequence encoding a human Igλ light chain inserted into an endogenous Igκ light chain locus of said non-human animal. Methods for producing antibodies from non-human animals are also provided, said antibodies containing a human variable region and a mouse constant region.

A genetically modified mouse is provided, wherein the mouse expresses a repertoire of immunoglobulin light chains characterized by a limited number of light chain variable domains. Mice are provided that exhibit a selection of two human light chain variable region gene segments, such that the immunoglobulin light chains expressed by the mouse comprise one of the two human light chain variable region gene segments. Methods are provided for generating bispecific antibodies having universal light chains using mice described herein, comprising the human light chain variable regions. Methods are provided for generating human variable regions suitable for use in multispecific binding proteins, e.g. bispecific antibodies, as well as host cells.

The invention provides a method of quantifying the amount of kappa or lambda immunoglobulin light chain in a sample from a subject comprising: i. providing a sample from a subject; ii. mixing the sample with a predetermined amount of lambda light chain calibrator or kappa light chain calibrator to form a mixture; iii. performing mass spectrometry on the mixture; and iv. quantifying one or both of a) the amount of lambda light chain in the sample by comparing the relative amount of lambda light chain in the mixture as determined by the mass spectrometry to the relative amount of calibrator kappa light chain in the mixture as determined by mass spectrometry; and / or b) the amount of kappa light chain in the sample by comparing the relative amount of kappa light chain in the mixture as determined by mass spectrometry to the relative amount of calibrator lambda light chain in the mixture as determined by mass spectrometry, most typically MALDI-TOF spectrometry or liquid chromatography-mass spectrometry.

The present invention relates to methods for enhancing an adoptive cell transfer immunotherapy that targets an immunoglobulin light chain by administering a protein that has IgG cysteine protease or IgG endoglycosidase activity.

Provided is a human immunoglobulin light chain transgene construct that encodes two different rearranged light chain VJ regions, arranged in such a way that one of the two alternative light chains is expressed from the construct upon recombination in B cells. Also provided is a transgenic animal containing the transgene. Thus, the binary light chain transgene allows the expression of two alternative fixed light chains in the animal. Also provided is a method for using the transgenic animal.

Disclosed are compositions and methods for in vivo genetic engineering of lymphocyte precursors. A lipid nanoparticle (LNP), surface-functionalized for lymphocyte precursor targeting, encapsulates a DNA payload comprising a therapeutic gene flanked by engineered Recombination Signal Sequences (RSS). The RSS spacer incorporates at least one non-natural nucleotide, reducing integration risks. Because RAG1 and RAG2 are expressed only after commitment to the lymphoid lineage, integration is restricted to immune precursors and cannot occur in stem cells or reproductive cells. Upon systemic delivery, the endogenous RAG1 / RAG2 complex integrates the payload into the precursor genome. Modified precursors undergo clonal expansion in vivo, amplifying the therapeutic effect from relatively low doses. In certain embodiments, the DNA payload encodes receptors or antibodies that specifically recognize aggregated amyloid proteins, including transthyretin (TTR) fibrils and immunoglobulin light- chain aggregates, enabling therapeutic treatment of amyloidosis. However, the platform is not limited to amyloidosis and can be applied to oncology, infectious diseases, autoimmune disorders, and other protein misfolding conditions.

The present invention relates to animals and methods of producing antibodies. Specifically provided is a nucleic acid construct comprising a portion of a V region and a portion of a J region of a light chain Kappa variable region locus of human immunoglobulin. The nucleic acid constructs of the invention are useful in the production of antibodies or animals with limited immune light chains.