32 results about "Human immunoglobulins" patented technology

Disclosed herein are kits and methods for treating pulmonary arterial hypertension (PAH), comprising administering to a subject in need thereof: •a therapeutically effective amount of a tyrosine kinase inhibitor or a pharmaceutically acceptable salt thereof; and•a therapeutically effective amount of a dimeric fusion protein comprising: •the extracellular domain of the activin type 2A (ACTR IIA) or the activin type 2B receptor (ACTR IIB); and the Fc domain of human immunoglobulin G1 (IgG1). In some embodiments, the tyrosine kinase inhibitor is Seralutinib or a pharmaceutically acceptable salt thereof and the fusion protein is Sotatercept.

Disclosed is a genetically modified rodent, in which an immunoglobulin light chain locus is modified to insert a human immunoglobulin light chain gene segment. The rodent is capable of normal reproduction and of producing antibodies containing human light chains. Further provided are a method for preparing the genetically modified rodent and the use.

The present invention discloses a genetically modified rodent whose immunoglobulin light chain locus is modified so as to comprise a single rearranged human immunoglobulin light chain gene V / J gene upstream of a mouse Kappa light chain locus constant region, a mouse variable region sequence cannot bind to an endogenous constant region to form a complete mouse light chain antibody, the rodents are capable of normally reproducing and producing human light chain-containing antibodies. The invention also provides a method of making the genetically modified rodent and a use of the rodent.

Genetically modified mice whose immunoglobulin loci are engineered to be inserted into gene segments of human immunoglobulin variable regions are disclosed, the mice being capable of normal reproduction and producing human-mouse chimeric antibodies comprising a human variable region and a mouse constant region. The invention also provides a method for preparing the genetically modified mouse and application of the mouse.

The invention relates to stable coformulations of antibodies or antigen-binding fragments thereof that bind to human immunoglobulin-like transcript 4 (ILT4) and PD-1. Also provided are methods of treating various cancers using the formulations disclosed herein.

Human immunoglobulin light chain transgene constructs are provided that encode at least two different rearranged light chain V-J regions arranged in such a manner that only one of the alternate light chains is expressed from the construct upon recombination in B cells. In some embodiments, the transgene comprises two, three or four different rearranged light chain V-J regions. Transgenic animals comprising the transgene are also provided. The light chain transgenes thus allow for expression of two, three or four alternate fixed light chains in the animals. Methods of using the transgenic animals are also provided.

Levels of expression of antibiotic resistance genes are increased up to six-fold by inserting a proteasome-targeting tag into transgenes expressed in eukaryotic cells. Various selectable marker proteins are combined with different destabilization domains, leading to up to 70% increase in transgene expression. The increase in expression varies highly depending on the engineered construct and the lines cells used. Increase in expression drives exosome loading of cargo proteins in some aspects. By increasing expression and by editing trafficking signals of cargo proteins, proteins that normally locate to the ER can be trafficked to exosomes. This disclosure discloses efficient exosome delivery of a wide variety of engineered proteins, including modified antigen proteins of SARS-CoV-2 and influenza, and other proteins such as a modified alpha galactosidase A, an extracellular domain of vascular endothelial growth factor fused to a constant region of a human immunoglobulin heavy chain, and modified trastuzumab heavy and light chains.

Disclosed in the present invention is a genetically modified mouse in which the immunoglobulin locus is engineered to be inserted with a gene segment of a human immunoglobulin variable region. The mouse is capable of reproducing normally and producing a human-mouse chimeric antibody, wherein the human-mouse chimeric antibody contains a human variable region and a mouse constant region. Further provided in the present invention is a method for preparing the genetically modified mouse and the use of the mouse.

A human immunoglobulin heavy chain transgene construct is provided that encodes a long CDR3 region. The heavy chain transgene comprises multiple VH regions that are longer than average and operably linked to multiple DD fusion segments. Transgenic animals containing the transgene are also provided. Methods for using the transgenic animals are also provided.

Provided is a method for producing an antibody and the antibody produced by the method. The method includes immunizing an animal transplanted with stems cell with differentiation potential using an antigen and obtaining an antigen-specific antibody. The stem cells with differentiation potential are derived from a donor animal carrying one or more human immunoglobulin variable region gene segments. The method solves problems in the prior art including long transportation time and high costs associated with live transgenic animals used for producing human antibodies due to policy and quarantine requirements. When producing antibody against a target antigen having high homology with a transgenic animal, an immunosuppressed animal with a target antigen-encoding gene knockout is used as a transplantation recipient, which solves the problem in the prior art where transgenic animals have difficulty generating antibodies against homologous regions of the target antigen between humans and transgenic animals.

The present invention provides, among other aspects, methods and compositions for treating a central nervous system (CNS) disorder by delivering a therapeutically effective amount of a composition of pooled human immunoglobulin G (IgG) to the brain via intranasal administration of the composition directly to the olfactory epithelium of the nasal cavity. In particular, methods and compositions for treating Alzheimer's disease are provided.

A human immunoglobulin heavy chain transgene construct encoding a long CDR3 region is provided. The heavy chain transgene comprises a plurality of VH regions longer than an average value, which are operably linked to a plurality of D-D fusion segments. Transgenic animals comprising the transgene are also provided. Methods of using these transgenic animals are also provided.

A genetically modified mouse is provided, wherein the mouse is incapable of rearranging and expressing an endogenous mouse immunoglobulin light chain variable sequence, wherein the mouse expresses only one or two human light chain variable domains encoded by human immunoglobulin sequences operably linked to the mouse kappa (κ) constant gene at the endogenous mouse κ locus, wherein the mouse expresses a reverse chimeric antibody having a light chain variable domain derived from one of only two human light chain variable region gene segments and a mouse κ constant domain, and a human heavy chain variable domain and a mouse heavy chain constant domain, from an endogenous mouse heavy chain locus. Bispecific epitope-binding proteins that are fully human are provided, comprising two different heavy chains that associate with an identical light chain that comprises a variable domain derived from one of two different human light chain variable region gene segments.

Disclosed in the present disclosure is genetically modified mice in which immunoglobulin loci are modified to insert gene segments of a human immunoglobulin variable region. The mice can be bred normally and produce human-mouse chimeric antibodies including a human variable region and a mouse constant region. The present disclosure also provides a method for preparing the genetically modified mice and use of the mice.

Non-human animals, tissues, cells, and genetic material are provided that comprise a modification of an endogenous non-human heavy chain immunoglobulin sequence and that comprise an ADAM6 activity functional in a mouse, wherein the non-human animals express a human immunoglobulin heavy chain variable domain and a cognate human immunoglobulin λ light chain variable domain.

Disclosed in the present invention is a genetically modified mouse in which the immunoglobulin locus is engineered to be inserted with a gene segment of a human immunoglobulin variable region. The mouse is capable of reproducing normally and producing a human-mouse chimeric antibody, wherein the human-mouse chimeric antibody contains a human variable region and a mouse constant region. Further provided in the present invention is a method for preparing the genetically modified mouse and the use of the mouse.

The present disclosure provides methods of treating PD-L1 negative tumors, the methods comprising administering fusion proteins comprising the extracellular domain of human cluster of differentiation 80 (CD80) and the fragment crystallizable (Fc) domain of human immunoglobulin G 1 (IgG1).

This invention belongs to the field of biomedicine, and particularly relates to respiratory syncytial virus (RSV) F protein mutants and their applications. The RSV F protein mutants include at least one pair of amino acid residues in the F1 and / or F2 subunits of the F protein polypeptide being replaced by cysteine, and / or the F protein signal peptide being replaced by a human immunoglobulin light chain signal peptide, and / or the polybasic sequence having alanine A at position 107 mutated to arginine R and lysine K at position 134 mutated to arginine R. This allows for the exposure of more neutralizing antibody epitopes, ensuring effective neutralizing antibody responses and antibody binding responses against RSV subtypes A and B while maintaining a stable pre-fusion conformation. It is suitable for various vaccine formulations using RSV F protein as an antigen.

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.

Disclosed in the present disclosure is genetically modified mice in which immunoglobulin loci are modified to insert gene segments of a human immunoglobulin variable region. The mice can be bred normally and produce human-mouse chimeric antibodies including a human variable region and a mouse constant region. The present disclosure also provides a method for preparing the genetically modified mice and use of the mice.

The present invention discloses a recombinant herpes simplex virus type I vaccine and its application, belonging to the field of vaccine technology. Specifically, it relates to a fusion protein composed of an antigen molecule gD1, a human immunoglobulin antibody Fc domain and a human IgG1 hinge region fragment, wherein the amino acid sequence of the antigen molecule gD1 is shown in SEQ ID NO.6, and a recombinant vaccine is constructed. The recombinant vaccine of the present invention fuses viral antigens, immunoglobulin heavy chain Fc domain and human IgG1 hinge region fragment, has a better ability to bind to receptors on the surface of antigen-presenting cells, and can activate specific CD4 + T and CD8 + T cells, producing high titer antibody titers and specific cellular immunity. This vaccine can prevent infection and / or reinfection with herpes simplex virus type 1.

Non-human animals, tissues, cells, and genetic material are provided that comprise a modification of an endogenous non-human heavy chain immunoglobulin sequence and that comprise an ADAM6 activity functional in a mouse, wherein the non-human animals express a human immunoglobulin heavy chain variable domain and a cognate human immunoglobulin λ light chain variable domain.

The invention provides a signal peptide combination for improving antibody expression quantity, a recombinant expression vector, a recombinant cell and application, and belongs to the technical field of bioengineering. According to the invention, three signal peptides SP-A, SP-B and SP-C with good expression are combined pairwise and fused with an Inflixi or human immune globulin antibody in Chinese hamster ovary cells for expression. Compared with the original carrier signal peptide, the combined signal peptide has the advantages that the antibody expression quantity is obviously improved, and the problem of low antibody expression quantity is solved. The antibody produced by the method is high in yield and convenient for industrial application.

The invention discloses a microcarrier for in-vitro amplification of mesenchymal stem cells. The microcarrier comprises a microsphere matrix formed by a biocompatible synthetic polymer, a nitrogen-containing functional group layer formed on the surface of the microsphere matrix, and recombinant human RGD-Fc fusion protein covalently linked to the nitrogen-containing functional group layer. Wherein the nitrogen-containing functional group layer is obtained through ammonia plasma treatment, the recombinant human RGD-Fc fusion protein contains a human RGD peptide fragment and a human immunoglobulin Fc structural domain, and the microcarrier does not contain any animal source component. The microcarrier can support stable amplification of mesenchymal stem cells to the eighth generation or above in a serum-free and animal-source-free culture system, and the cell phenotype positive rate is not lower than 90%. The invention solves the problems of heterologous risk, batch instability and non-specific adhesion of the existing animal-derived microcarrier, and is suitable for large-scale production of clinical-grade cell therapy products.

Genetically modified mice whose immunoglobulin loci are engineered to be inserted into gene segments of human immunoglobulin variable regions are disclosed, the mice being capable of normal reproduction and producing human-mouse chimeric antibodies comprising a human variable region and a mouse constant region. The invention also provides a method for preparing the genetically modified mouse and application of the mouse.

This invention provides a monoclonal antibody that is universally specific to human IgG but does not bind to monkey IgG. [Solution] An anti-human IgG antibody obtained from rabbits, its antigen-binding portion, and a method for using the antibody and portion are provided.

Disclosed is a genetically modified rodent an immunoglobulin light chain locus of which is engineered such that a single rearranged human immunoglobulin light chain gene V / J gene is contained upstream of a constant region of the mouse Kappa light chain locus, and thus a mouse variable region sequence cannot bind to the endogenous constant region to form a complete mouse light chain antibody. The rodent can reproduce normally and produce an antibody containing a human light chain. Also provided are a preparation method for the genetically modified rodent and the use thereof.

The present disclosure related to chimeric antigen receptors (CARs) comprising immunoglobulin (Ig) derived spacers, e.g., hinge or loop regions, fragments thereof, or combinations thereof. Ig derived spacer confers improved properties to the CARs, e.g., increased cytokine release with respect the CARs with spacers not derived from hinge regions and fragments thereof, loop regions from constant domains and fragments thereof, and combinations thereof. Also provided are cells expressing CARs comprising Ig derived spacers regions and methods to use the CARs to treat diseases or disorders, e.g., cancer. Some of the disclosed Ig derived spacers are fragments from, e.g., IgAQ1, IgA2, IgD, IgE, IgG1, IgG2, IgG3, IgG4, or IgM. In some aspects, the disclosed Ig derived spacers are derived from non-human immunoglobulins, e.g., mouse immunoglobulins such IgG2A. Other Ig derived spacer disclosed are modular constructs comprising several concatenated Ig hinges or fragments thereof.

Human immunoglobulin light chain transgene constructs are provided that encode at least two different rearranged light chain V-J regions arranged in such a manner that only one of the alternate light chains is expressed from the construct upon recombination in B cells. In some embodiments, the transgene comprises two, three or four different rearranged light chain V-J regions. Transgenic animals comprising the transgene are also provided. The light chain transgenes thus allow for expression of two, three or four alternate fixed light chains in the animals. Methods of using the transgenic animals are also provided.

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.