699results about "Interleukins" patented technology

The present disclosure relates to IL12 receptor agonists with improved therapeutic profiles.

The invention relates generally to compositions and methods for purifying the desired species from a mixture of desired heterodimer and contaminating homodimer immunoglobulin variants by modifying the isoelectric point(s) of the individual chains.

The present invention relates to antibody-cytokine conjugates, wherein the cytokine is conjugated to the antibody via a cleavable linker. Conjugates according to the invention can be prepared by coupling a functionalized antibody Ab (F) x comprising x reactive moieties F, where x is an integer in the range of 1-10, with an immune cell-binding polypeptide comprising one or two reactive moieties Q, where the antibody is specific for tumor cells, and the immune cell-binding polypeptide is specific for immune cells, wherein the reaction forms a covalent bond between the functionalized antibody and the immune cell-binding polypeptide by reaction of Q with F. The invention further relates to antibody-cytokine conjugates obtainable by the method according to the invention and to medical uses thereof.

The invention relates to proximity activated cytokine compounds comprising a PD-1 targeting moiety, and an IL-21 polypeptide covalently linked to an anti-IL-21 antibody-binding domain, which together provide targeted cytokine signaling to PD-1 expressing cells. The invention further relates to nucleic acid and expression vectors encoding proximity activated cytokines, as well as use of such compounds for treating cancer.

Provided herein are chimeric antigen receptors (CARs) for cancer therapy, and more particularly, CARs containing a scFv from an anti-ROR-1 monoclonal antibody. Provided are immune effector cells containing such CARs, and methods of treating proliferative disorders.

The present disclosure provides a population of CD4IL-10 / CAR cells (autologous or allogeneic single-donor and allogeneic polydonor) generated by genetically modifying CD4+ Tcells to express IL-10 and a chimeric antigen receptor. Further provided are methods of generating the CD4IL-10 / CAR cells and methods of using the CD4IL-10 / CAR cells for immune tolerization, treating GvHD, cell and organ transplantation, cancer, and autoimmune and inflammatory disorders.

The present disclosure provides drug responsive domains derived from human carbonic anhydrase 2 that can modulate protein stability for human interleukin 15 (IL15) payloads, as well as compositions and methods of use thereof.

Systems and methods are presented that provide for improved NK cell function. In preferred aspects, NK-92 cells express recombinant er / LSP-IL-15 to so render the NK-92 cells independent of exogenous cytokines and to provide extracellular immune stimulation.

The present invention is directed to novel targeted heterodimeric fusion proteins comprising an IL-15 / IL-15Rα Fc-fusion protein and a LAG-3 antibody fragment-Fc fusion protein.

An improved method of treating cancers with engineered T cells is described.

Provided is a bispecific antibody and use thereof, the bispecific antibody comprising: a first domain that specifically binds the interleukin-6 receptor IL-6R, and a second domain that specifically binds interleukin-23. The bispecific antibody can simultaneously target IL-6R and IL-23p19, with stronger specificity, more accurately targeting tumor cells and reducing the adverse effects of off-target toxicity and can perform a unique function to play a biological function that is difficult to achieve with monoclonal antibody drugs. Compared with monoclonal antibody combination therapies, it can also effectively reduce the cost of treatment and break the current upper limit of therapeutic efficacy in the treatment of autoimmune diseases such as rheumatoid arthritis and IBD.

The present disclosure relates to methods and compositions for treating cancer using inducible IL-12 prodrugs.

The present disclosure relates to a class of engineered polypeptides having a binding affinity for interleukin-17A (IL-17A), and provides an IL-17A binding polypeptide comprising the sequence EX2DX4AX6X7EIX10X11LPNL X16X17X18QX20X21AFIX25 X26LX28X29. Also disclosed is the use of such an interleukin-17A binding polypeptide as a diagnostic, prognostic and / or therapeutic agent.

The invention belongs to the technical field of biological pharmacy, and relates to a bifunctional fusion protein targeting PD-1 / PD-L1 and IL-33 as well as a construction method and application of the bifunctional fusion protein. The bifunctional fusion protein comprises a PD-1 / PD-L1 antibody and a targeted IL-33 functional fragment, T cells are activated by blocking a PD-1 / PD-L1 signal to kill tumor cells, meanwhile, the level of IL-33 in tumor tissue is reduced, and the activity of IL-33 is inhibited. Researches show that the bifunctional fusion protein can increase infiltration of functional T cells, enhance T cell response and remodel a tumor microenvironment so as to generate an anti-tumor effect superior to that of combined treatment, and has a very good application prospect.

To provide cytokine muteins and cytokine prodrugs, and methods of making and using same.SOLUTION: Provided is a prodrug comprising a cytokine moiety, a masking moiety and a carrier moiety, where the masking moiety is linked to the cytokine moiety to inhibit the biological activity of the cytokine moiety, the cytokine moiety is fused to the carrier moiety, the cytokine moiety comprises the IL-15 polypeptide or a functional fragment thereof, the masking moiety is fused to the cytokine moiety or the carrier moiety via a cleavable peptide linker, the masking moiety comprises the extracellular domain (ECD) of a receptor of the cytokine moiety, the carrier moiety is an antibody Fc domain or an antibody comprising knobs-into-holes mutations, and the cytokine moiety and the masking moiety are fused to different polypeptide chains of the antibody Fc domain or to the different heavy chains of the antibody.SELECTED DRAWING: None

The present invention relates to multispecific antigen binding proteins that comprise an antigen-binding regions specific for a tumor-associated antigen (TAA), an antigen-binding region that specifically binds an epitope of a γδ T cell receptor (TCR), a γδ T cell-activating cytokine, and optionally, a γδ T cell co-stimulatory agonist. The γδ T cell-activating cytokine preferably is at least 5 one of an interleukin 21 receptor (IL21R) agonist and an interleukin 15 receptor (IL15R) agonist. The γδ T cell co-stimulatory agonist cytokine preferably is at least one of a 4-1BB agonist, a CD27 agonist and a GITR agonist. The multispecific antigen binding proteins of the invention specifically redirect and activate γδ T cell to lyse targeted tumor cells. The invention further relates to the use of such multispecific antigen binding proteins in the treatment of cancer, preferably a cancer 10 expressing the TAA.

An object of the present invention is to provide a small molecule compound (IL-17 activity inhibitor) having a more potent inhibitory effect on IL-17 activity than conventional compounds. The IL-17RA inhibitor of the present invention is, for example, a small molecule compound surrounded by Phe60, Gln87, Asp121, Pro122, Asp123, Gln124, Asp153, Cys154, Glu155, Lys160, Pro164, Cys165, Ser167, Ser168, Gly169, Ser170, Leu171, Trp172, Asp173, Pro174, Pro254, Phe256, Ser258, Cys259, Asp262, Cys263, Leu264, and His266, which are contained in the extracellular domain of human interleukin-17 receptor A (IL-17RA). The compound contains a compound having the effect of inhibiting the binding of interleukin-17A (IL-17A) to IL-17RA in humans, etc., or a pharmaceutically acceptable salt, solvate, or prodrug thereof, which can bind to IL-17RA through non-covalent interactions, including van der Waals forces acting between at least 13 of these amino acid residues in the space defined by the compound, and preferably further including at least one type of intermolecular interaction selected from the group consisting of ionic bond, hydrogen bond, C-H-π interaction, and hydrophobic interaction acting between predetermined ones of the amino acid residues.

The present invention relates to multispecific antigen binding proteins that comprise antigen-binding regions specific for a tumor-associated antigen (TAA) and NK cell-activating cytokines. The NK cell-activating cytokine preferably is at least one of an interleukin 21 receptor (IL21R) agonist and a 4-1BB agonist. The multispecific antigen binding protein can further comprise an antigen-binding region that has affinity for a surface antigen expressed on NK cells, e.g CD16A. The multispecific antigen binding proteins of the invention specifically redirect and activate NK cells to lyse targeted tumor cells. The invention further relates to the use of such multispecific antigen binding proteins in the treatment of cancer, preferably a cancer expressing the TAA.

An immunogenic fusion protein used for active immunization or a bivalent vaccine in the treatment of atopic dermatitis (AD) in a subject and a method thereof. The immunogenic fusion protein includes a IL31 polypeptide and at least one substance P polypeptide (SP). The invention is particularly useful for treating and / or preventing AD and symptoms related to AD including pruritus in mammals.

The present disclosure provides IL-15 variants and heterodimeric IL-15 / IL-15Rα-Fc fusion proteins comprising the IL-15 variants, methods of producing the same, and uses thereof. The provided IL-15 variants and fusion proteins can be effective agents for treating cancer.

The present disclosure provides a formulation of an IL-12-albumin binding domain (ABD) fusion protein comprising a fusion protein of about 10 μg / mL to about 50 μg / mL, about 25 mM to about 100 mM alanine, about 100 mM to about 400 mM trehalose, about 10 mM to about 50 mM glycylglycine, about 0.01% to about 0.04% polysorbate 20 (v / v), and about 5 μM to about 20 μM diethylenetriaminepentaacetic acid (DTPA), and the formulation has a pH of about 6.8 to about 8.0. Such a formulation may be useful for treating and / or preventing an IL-12 related disease or disorder in a subject in need of treatment of an IL-12 related disease or disorder.

Provided herein are macromolecules that conditionally induce a cellular effector function (e.g., a biological or therapeutic activity) based on the presence of a disease signature ligand, compositions comprising the same, and methods of using the same.

The present invention provides a novel fusion protein for the treatment of autoimmune diseases that significantly reduces the expression of pro-inflammatory cytokines without side effects and demonstrates excellent therapeutic efficacy against various autoimmune diseases.

Provided are methods of diagnosis and treatment of atopic dermatitis.

The present disclosure relates to toxin-derived delivery constructs, in particular isolated non-naturally occurring delivery constructs, for oral delivery, comprising a bacterial toxin-derived delivery construct coupled to a biologically active therapeutic cargo; wherein the delivery construct is capable of delivering a bioactive cargo through epithelial cells via endocytotic transport; and wherein the delivery construct does not comprise a bacterial toxin-derived translocation domain or a bacterial toxin-derived catalytic (cytotoxic) domain.

The invention relates to a specific antibody aiming at CD228 protein and an antigen binding fragment thereof, which are used for detecting and treating various tumors, such as melanoma, mesothelioma, colorectal cancer and the like. The antibody binding fragment is helpful for diagnosis and treatment of cancers through specific binding with CD228. The invention further comprises antibody drug conjugates (ADCs) which bind a drug to an antibody through a linker, so as to improve the therapeutic effect and reduce the influence on normal cells. Meanwhile, nucleic acids encoding the antibodies or antigen-binding fragments thereof are provided to produce recombinant antibodies or fragments. Besides, the invention also provides a kit which is used for laboratory research, clinical diagnosis and treatment effect monitoring, is beneficial to determining whether tissues or cells express CD228 or not, and provides a new strategy for personalized and precise treatment of cancers.

Anti-SLAMF7 Fab fragments, antibodies, biparatopic antibodies, and chimeric antigen receptors (CARs) are provided herein. Also provided are polynucleotides encoded the anti-SLAMF7 Fab fragments, antibodies, biparatopic antibodies, and CARs. The anti-SLAMF7 Fab fragments, antibodies, biparatopic antibodies, and CARs are useful for the prevention and / or treatment of cancer, such as multiple myeloma. Also provided is a combination therapy including administration of the anti-SLAMF7 Fab fragments, antibodies, biparatopic antibodies, and CARs with an IL-16 or an IL-15 agonist.

The invention is related to methods of treatment of active psoriatic arthritis (PsA). In certain embodiments, the invention provides pharmaceutical compositions of izokibep and uses thereof for treatment of active psoriatic arthritis.

Compositions for treating cancer are provided, which comprise an immunoconjugate in combination with a chemotherapeutic agent. Methods for treating cancer are also provided, which include the use of the compositions.

This specification describes methods using fusion proteins comprising one or more elements such as proteins / polypeptides capable of translocating to the endoplasmic reticulum (ER) and interleukin-18 (IL-18) or fragments or variants of IL-18. Examples of ER-translocating proteins / polypeptides include, but are not limited to, Fc regions, VHH antibodies, immunoglobulin-like proteins such as scFv, and globular proteins such as serum albumin. IL-18 may also be a precursor IL-18 similar to a native procytokine in which IL-18 is fused to the C-terminus of its propeptide or propeptide variant. These fusion proteins activate IL-18 receptor complex (RC) signaling on cells, release or expose mature IL-18 in or adjacent to the tumor microenvironment, and / or memory CD8 - It may be used in methods of treating cancer or fibrosis by increasing T cell proliferation.