36 results about "Intravenous IG" patented technology

Provided herein are gene editing systems and compositions directed to effectuate in vivo edits in the LPA gene. Treatment or prevention of cardiovascular disease through disruption of the production of apo(a) through genetic editing and the reduction of the blood lipoprotein(a) [Lp(a)] concentration is disclosed herein. Disclosed are nickase-based gene editing systems designed to effectuate the installation of insertions and / or deletions (indel variants) and / or non-synonymous variants in the coding sequence of LPA. The nickase-based gene editing systems generally comprise one or more mRNAs that encode one or more nickases and a plurality of guide oligonucleotides (e.g., gRNAs) and may be delivered in vivo to a mammalian subject in need thereof via a suitable delivery system, such as lipid nanoparticles (LNPs) (with or without GalNAc targeting moieties) intravenously, or otherwise, administered to a patient as potentially a once-and-done therapeutic. The manufacturing, use, and formulation of the gene editing systems and compositions are also disclosed.

Activation of STimulator of INterferon Genes (STING) triggers cytokine production and facilitates tumor antigen cross-presentation. In an embodiment of the present invention, STING-dependent innate immune signaling pathway activators (STAVs) together with Replicants including mRNA adapted to express an antigen can be delivered to antigen presenting cells (APC's) using lipid nanoparticle formulations. In various embodiments of the present invention, the range of cancers amenable to STAV / Replicant therapy can be extended using a non-cell-based nanoparticle strategy that effectively delivers the STAV / Replicant into the Tumor Micro Environment (TME) to potently generate anti-tumor cytotoxic T cell activity together with humoral immune responses. The STAV / Replicant formulations can be introduced into solid tumors present in the subject. Alternatively, the STAV / Replicant can be introduced through direct inoculation, intramuscularly, or intravenously. The lipid nanoparticles stick to the tumor cells and are co-phagocytosed to activate STING in APCs.

The invention relates to a cell membrane bionic drug-loaded carbon dot nano-material as well as a preparation method and application thereof. The nano-composite is prepared by the following steps: preparing carbon dots, cross-linking to form a reduction responsive carbon dot nano-cluster, sequentially loading chemotherapeutic drugs and coating a cancer cell membrane to form a nano-vaccine. After the nano vaccine is injected into the body of a mouse through caudal vein, the enrichment of the nano vaccine in a tumor part can be enhanced by utilizing the active tumor targeting characteristic of a cancer cell membrane, and tumor cells can be induced to generate immunogenic death through carried chemotherapy drugs and photothermal therapy, so that chemotherapy / photothermal / immune combined therapy on tumors is realized; the obvious anti-tumor effect is realized. In addition, as a nano vaccine, after subcutaneous injection, the nano vaccine can also utilize the tumor antigen carried by a cancer cell membrane and the adjuvant characteristics of the carbon dots to activate the anti-tumor immunity of an organism so as to prevent tumors, and has potential clinical application value.

This invention discloses a method for preparing NK cells, the NK cells obtained thereby, and their applications. The method includes: sorting NK cells from peripheral blood of an allogeneic donor; culturing them in a serum-free medium containing CD3 monoclonal antibody, CD16 antibody, and IL-2, without the need for a feeder layer; preferably, IL-21 is added for amplification on days 3-5 of culture, and the cells are cultured for 20-40 days. This method yields non-genetically modified NK cells, among which CD56... bright The NK cells comprise >90% of the cell line and highly express a variety of activating and functional molecules. These NK cells effectively clear Aβ oligomers and senescent cells, and alleviate neuroinflammation. In treatment, intracranial injection achieves equivalent or better efficacy with only about 1 / 10th the dose administered intravenously, significantly clearing Aβ deposits in the brains of AD model mice and improving pathology.

The present invention provides intravenous pharmaceutical compositions comprising engineered plant virus-based nanoparticles for the treatment or prevention of autoimmune conditions. The nanoparticles display immunodominant peptides that induce immune tolerance in a subject when administered intravenously. The invention further provides methods of manufacturing virus-based nanoparticles, including production in plant expression systems and optional viral inactivation, to render them suitable for therapeutic use in mammals. Also provided are methods of intravenous administration of the pharmaceutical compositions to a subject in need thereof for treating or preventing autoimmune conditions.

The invention belongs to the field of nucleic acid editing, and particularly relates to the technical field of regularly clustered interval short palindromic repeat (CRISPR). Specifically, Cas9 or smaller Cas-SF01 (a Cas12i3 variant) is utilized to reasonably design and construct a compact mRNA-delivered epigenetic suppressor in an engineering manner, and an optimized mRNA structure, lipid nanoparticle (LNP) delivery, OFF-E-V2 mRNA optimized by single intravenous injection and selected guide RNA (gRNA) targeting mouse PCSK9 are combined, so that circulating PCSK9 protein is reduced by about 90%, corresponding LDL-C level is reduced by about 55%, and the PCSK9 protein is reduced by about 90%. The effect lasts for at least 180 days. Compared with a corresponding object based on Cas9, an editor based on Cas-SF01 shows higher specificity, and off-target methylation events are fewer. The optimized LNP formulations also exhibit good safety. These findings establish a powerful and versatile platform for promoting a transient delivery-based engineered mRNA editor to achieve precise and lasting epigenetic silencing in vivo therapy.

The present invention relates to the treatment of diseases associated with inflammation including solid cancers. More particularly, certain methods relate to the administration (e.g., intravenously) of polyhedrin protein (PODS) crystals for the delivery of one or more therapeutic proteins. This enables targeted release of low doses of the therapeutic protein at sites of the disease.

This invention discloses a method for improving a mouse model of ANCA-associated vasculitis induced by anti-GBM antibodies, relating to the field of animal model construction. The method involves subcutaneously injecting mice with 20 μg rMPO on Day 0; administering 10 μg rMPO on Day 7; subcutaneously injecting 250 μg / kg GCSF daily from Day 11 to 15; and injecting 100 μl of goat anti-GBM serum via the tail vein on Day 16 to obtain the improved mouse model. This method improves the existing anti-GBM antibody-induced ANCA-associated vasculitis mouse model by injecting GCSF. This model enhances the disease severity in ANCA-associated vasculitis mice, specifically reflecting the disease in renal pathology and proteinuria, making the differences more obvious and effectively improving the success rate of model establishment.

Provided are methods for clinical treatment of complement-associated conditions comprising administering to the patient an anti-C5 antibody, or antigen binding fragment thereof, wherein the anti-C5 antibody, or antigen binding fragment thereof, is administered (or is for administration) subcutaneously according to a particular clinical dosage regimen (i.e., at a particular dose amount and according to a specific dosing schedule). In one embodiment, the patient has previously been treated with eculizumab (SOLIRIS®) or ravulizumab (ULTOMIRIS®); particularly intravenously administered SOLIRIS® or ULTOMIRIS®.

The present disclosure provides agents and methods for preventing or treating tuberculosis using RNA. The RNA encoding variants of antigens of Mycobacterium tuberculosis ox of fragments thereof is formulated and administered in a way that the variants are produced by cells of a subject, in particular after intramuscular or intravenous administration of the RNA.

The invention relates to the use of empty liposomes of defined lipid composition or mixtures of empty liposomes of defined lipid composition and to the use of other lipid bilayers or monolayers of defined lipid composition for the treatment and prevention of bacterial infections. It has been found that such liposomes, in particular a two- and a four-component mixture of liposomes comprising cholesterol and sphingomyelin, liposomes consisting of sphingomyelin, liposomes comprising sphingomyelin and phosphatidylcholine, and liposomes comprising cholesterol and phosphatidylcholine efficiently sequestrate a variety of toxins secreted by bacteria, thus preventing binding of bacterial toxins to target cells and toxin-induced lysis of the target cells. Injected intravenously, liposome mixtures prevented death of laboratory mice infected with lethal doses of Staphylococcus aureus or Streptococcus pneumoniae.

The application discloses application of recombinant human USP13 protein in preparation of a drug for treating diabetic cardiomyopathy, and belongs to the technical field of biological medicines.The application first proves that the expression of USP13 in myocardial tissue and serum is significantly reduced under the condition of diabetic cardiomyopathy (DCM); the recombinant human USP13 protein can obviously reduce the level of myocardial cell active oxygen, reduce the expression of NLRP3 inflammasome and active Caspase3 protein in a DCM in-vitro model induced by high sugar / palmitic acid; in a DCM mouse model injected with the recombinant human USP13 protein through a tail vein, myocardial cell apoptosis is inhibited, and the expression of NLRP3 inflammasome and the synthesis of TNF-alpha in the heart of the animal are reduced.USP13 is a human protein, has no obvious toxic side effects, is high in safety, is small in immunological rejection in theory, provides a new effective drug for the clinical treatment of DCM, and has important clinical application value and industrialization prospect.

The application provides a serum proteomics and machine learning-based Kawasaki disease intravenous immunoglobulin (IVIG) resistance biomarker combination and screening method, and belongs to the technical field of medicines. The method comprises the following steps: (1) on the basis of establishing strict inclusion criteria and typing criteria, collecting whole blood samples of IVIG reaction type and non-reaction type Kawasaki disease children before treatment; (2) using DIA proteomics technology for systematic screening and differential protein identification; (3) weighted co-expression network analysis, screening of protein modules significantly related to IVIG non-reaction phenotype; (4) combined with LASSO-Logistic regression and SVM-RFE for multi-step feature screening, identifying five biological markers significantly related to IVIG resistance: PLA2G4A, SNX17, PURB, CERS3 and CASP1 (5) based on the marker expression level, using the pROC package for ROC analysis and calculating AUC; (6) analyzing the correlation between the marker and the clinical index related to Kawasaki disease; (7) after limma processing in the independent transcriptome set GSE18606, using glm to construct a multivariate binary logistic regression prediction model and perform ROC analysis. Through independent transcriptome dataset verification, the biomarker combination screened by the application can realize effective prediction of Kawasaki disease IVIG resistance, and shows good prediction performance and clinical application value.

The application discloses a myocardial ischemic injury marker CAPG and application thereof. The application finds that down-regulation of CAPG expression can improve myocardial cell apoptosis and heart function after myocardial infarction by injecting AAV9-shCAPG virus into the tail vein of a mouse model of myocardial infarction. The application first discloses a new use of macrophage capping protein (CAPG) as a therapeutic target and a diagnostic target of myocardial ischemic injury, provides a new drug action target for diagnosis and treatment of myocardial ischemic injury, and has very important clinical transformation value. As a diagnostic marker of myocardial ischemic injury, CAPG can be conveniently detected by using an existing enzyme-linked immunosorbent assay kit, has the advantage of rapid detection, and can be conveniently detected by only extracting a small amount of peripheral venous blood of a patient.

Methods and kits for predicting infusion reaction risk and antibody-mediated loss of response during intravenous PEGylated uricase therapy in gout patients is provided. Routine SUA monitoring can be used to identify patients receiving PEGylated uricase who may no longer benefit from treatment and who are at greater risk for infusion reactions.

We provide therapeutic antibodies for the treatment of neurological diseases, particularly Alzheimer's disease. [Solution] A bispecific anti-Aβ / TfR antibody is provided for use as a pharmaceutical in the treatment of Alzheimer's disease, which specifically binds to human Aβ protein and human transferrin receptor (bispecific anti-Aβ / TfR antibody), and the antibody is administered intravenously once every four weeks at a dose of 0.2 mg / kg to 7.2 mg / kg.

This invention provides the use of a reagent overexpressing Parp7 in the preparation of drugs for treating septic cardiomyopathy, belonging to the field of biomedical technology. This invention involves constructing a recombinant adeno-associated virus vector AAV9-F4 / 80- that specifically overexpresses PARP7 on macrophages. Parp7 The drug was intravenously injected into mice, and a septic cardiomyopathy model was established using lipopolysaccharide induction. Experimental results showed that macrophage-specific overexpression of PARP7 significantly reduced serum levels of myocardial injury markers CK-MB and cTnT, improved cardiac function indicators such as ejection fraction and fractional shortening, alleviated myocardial tissue pathological damage, and inhibited macrophage infiltration and inflammatory factors. Ifn-beta , Tnf- α , Il‑6 and Il‑1β The expression of PARP7. This invention reveals the protective role of PARP7 in septic cardiomyopathy, providing a new target and strategy for the treatment of septic cardiomyopathy.

This specification provides gene editing systems and compositions aimed at achieving in vivo editing of the LPA gene. Treatment or prevention of cardiovascular disease by gene editing interference with apo(a) production and reduction of blood lipoprotein(a) [Lp(a)] concentration is disclosed herein. A nickase-based gene editing system designed to achieve insertion and / or deletion (indel variant) and / or non-synonymous variant introduction in the coding sequence of LPA is disclosed. A nickase-based gene editing system generally comprises one or more nickases and one or more mRNAs encoding multiple guide oligonucleotides (e.g., gRNAs), and may be delivered intravenously in vivo to a mammalian subject requiring it as a potentially one-time treatment via a suitable delivery system such as lipid nanoparticles (LNPs) (with or without a GalNAc targeting moiety), or administered by other means. The manufacture, use, and formulation of gene editing systems and compositions are also disclosed.

Methods and compositions of useful for removal and / or enhancing removal of senescent cells are provided. Methods of administration of premade antibody mixtures, such as intravenous immunoglobulin (IVIG) to stimulate clearance of senescent cells. IVIG is utilized to enhance efficacy of senolytic agents, whether they be small molecule, nucleic acids, or immunotherapy-based approaches. In another embodiment natural antibody producing cells, such as B1 cells are administered to a patient in which enhance clearance of senescent cells is desired.

We provide gene therapy for GLUT1 deficiency syndrome. [Solution] This specification provides gene therapy for GLUT1 deficiency syndrome and related disorders using recombinant adeno-associated virus (rAAV) virions as vectors for expressing the GLUT1 protein or a functional variant thereof. The rAAV virions may use endothelial-specific promoters, such as the FLT-1 or Tie-1 promoter. The capsid may be the AAV6, AAV8, AAV9, AAVrh.74, or AAVrh.10 capsid or a functional variant thereof. Other promoters or capsids may be used. Furthermore, methods for therapy using rAAV virions intracerebral and / or intravenously, as well as other compositions and methods, are provided.

The present application relates to a kind of multifunctional layered double hydroxide (LDH) based therapeutic nano vaccine and preparation method and application.The nano vaccine is loaded with immunoadjuvant CpG and chemotherapeutic drug 5-fluorouracil (5-FU) in turn with LDH as carrier, and further coated with apoptotic tumor cell membrane (aCM), to construct a nano vaccine with immune synergistic therapy function.After being injected into mouse body through tail vein, the LDH-based therapeutic nano vaccine realizes multi-mode combined therapy for tumor through the endoplasmic reticulum stress amplification effect mediated by calcium ion overload, through 5-FU to inhibit DNA synthesis and interfere RNA function in tumor cells, and through the synergistic immune activation mechanism mediated by the double adjuvant system composed of aluminum ion and CpG.The strategy not only significantly inhibits the growth of in situ tumor, but also can induce the body to produce immune memory, and plays an effective tumor prevention effect.

The invention relates to stable formulations of antibodies against human programmed death receptor PD-1, or antigen binding fragments thereof. In some embodiments the formulations of the invention comprise between 5-250 mg / mL anti-PD-1 antibody, or antigen binding fragment thereof, a buffer, a stabilizer, a surfactant, and an antioxidant in the amounts specified herein. In particular embodiments, the anti-PD-1 antibody is pembrolizumab. The invention further provides methods for treating various cancers with stable formulations of the invention. In some embodiments of the methods of the invention, the formulations are administered to a subject by intravenous or subcutaneous administration.

The present invention relates to novel use of an oncolytic virus, and relates to an intravenously injectable composition for repeated administration, comprising, as an active ingredient, an oncolytic virus in which expression of a thymidine kinase (TK) gene is suppressed and genes encoding complement regulatory protein CD55 and granulocyte-macrophage colony-stimulating factor (GM-CSF) are inserted. In detail, the present invention relates to an intravenously injectable composition for repeated administration, comprising, as an active ingredient, an oncolytic virus in which: expression of a TK gene is suppressed; and a gene encoding CD55 fused with a transmembrane domain region of viral membrane protein to enable the expression of the complement regulatory protein CD55 in an intracellular mature virion (IMV) membrane and a gene encoding the GM-CSF are inserted.

The invention relates to stable formulations of antibodies against human programmed death receptor PD-1, or antigen binding fragments thereof. In some embodiments the formulations of the invention comprise between 5-200 mg / mL anti-PD-1 antibody, or antigen binding fragment thereof. The invention further provides methods for treating various cancers with stable formulations of the invention. In some embodiments of the methods of the invention, the formulations are administered to a subject by intravenous or subcutaneous administration.

The invention relates to the field of animal immunity, in particular to a method for improving antigen immunogenicity. According to the invention, a high-homology antigen and a bacillus calmette-guerin vaccine are subjected to covalent coupling to form an antigen-bacillus calmette-guerin vaccine compound, and the antigen-bacillus calmette-guerin vaccine compound is immunized in an intravenous injection manner. The method is simple, fusion expression of protein or polypeptide and other proteins or coupling of a special costimulatory sequence is not needed, and the coupling method and the injection way are mature technologies in the industry. By referring to the method provided by the invention, the immunogenicity of the high-homology antigen can be obviously improved.

The application discloses an engineered intracellular antibody, which is fused by a Nef protein sequence of HIV-1 and an intracellular antibody sequence for targeting and degrading mutant huntingtin protein, and has simple structure and is easy to artificially synthesize. The application further discloses an exosome carrying the intracellular antibody, wherein a rabies virus glycoprotein peptide segment RVG is expressed on the membrane of the exosome, so that the exosome can specifically target nerve cells, and has high stability, low immunogenicity, and high penetration, and can be injected intravenously and cut to target and efficiently remove the existing mutant huntingtin protein and its aggregates in the brain of a patient, solve the off-target problem of gene therapy, and have important significance for removing the existing mutant huntingtin protein and its aggregates in the brain of a patient with late Huntington's disease.

The invention provides dosage regimes for treatment of synucleinopathies. In one regime, a subject receives 3000-5000 mg of an antibody intravenously every 3-5 weeks. In another regime, a subject receives 1300-1700 mg of an antibody intravenously every 3-5 weeks.

Methods and kits for predicting infusion reaction risk and antibody-mediated loss of response during intravenous PEGylated uricase therapy in gout patients is provided. Routine SUA monitoring can be used to identify patients receiving PEGylated uricase who may no longer benefit from treatment and who are at greater risk for infusion reactions.