25 results about "Interleukin 12" patented technology

Activatable interleukin 12 (IL12) fusion proteins and constructs are disclosed herein that contain at least one of the following structures: N'-DD-L1-MM-L2-IL12-C', C'-DD-L1-MM-L2-IL12-N', N'-DD-L1-IL12-L2-MM-C', C'-DD-L1-IL12-L2-MM-N', wherein L1 is a first linker or is absent; L2 is a second linker; DD is a dimerization domain; MM is a masking moiety; IL12 comprises an IL12α (p35) domain and an IL12β (p40) domain; N' is an amino terminus of the activatable IL12 fusion protein; and C' is a carboxy terminus of the activatable IL12 fusion protein, wherein at least one of L1 and L2 comprises a cleavable moiety (CM); or a first IL12 subunit and a second IL12 subunit; at least one of a first linking region (LR1) and a second linking region (LR2); and a half-life extending moiety (EM), wherein at least one of the LR1 and the LR2 comprises a cleavable moiety (CM); or dimers thereof.

The technical problem is to develop a novel armed oncolytic herpes simplex virus (HSV) with G47 delta as a skeleton. Provided is a pharmaceutical composition containing an IL-12 expression-type genetically recombinant herpes simplex virus (HSV) that has a gene encoding a fusion polypeptide in which a 35 kDa light chain (p35) and a 40 kDa heavy chain (p40) of interleukin 12 (IL-12) are linked by two or more elastin motifs, and that has the following characteristics (a) to (c). (a) the ICP6 gene is deleted or inactivated; (b) deletion or inactivation of the gamma34.5 gene; and (c) the alpha 47 gene is deleted or inactivated.

The present invention refers, inter alia, to i) a mutein of the α-subunit of human Interleukin 12 (hIL-12), wherein at least one of the amino acid residue(s) of said α-subunit of hIL-12 selected from the group consisting of sequence position(s) 70, 71, 72, 185, 187 and 189 is / are mutated, ii) a mutein of the β-subunit of hIL-12, wherein at least one of the amino acid residue(s) of said β-subunit of hIL-12 selected from the group consisting of sequence position(s) 37, 38, 39, 67, 81, 82, 103, 106, 115, 122, 123, 216, 221, 232 and 312 is / are mutated, iii) a mutein of hIL-12, comprising an α-subunit (p35) and a β-subunit (p40), wherein the α-subunit is a mutein of the α-subunit of hIL-12 according to the present invention, and / or wherein the β-subunit is a mutein of the β-subunit of hIL-12 according to the present invention, and iv) uses thereof.

Pharmaceutical compositions comprising anti-interleukin 12 (IL-12) interleukin 23 (IL-23) antibodies are described. The pharmaceutical compositions may comprise molecular attributes, such as oxidation of light chain W32, isoaspartic acid at heavy chain position D55; high molecular weight species such as dimers and / or oligomers, high mannose, sialylation, or acidic peak species. Method comprising administering the pharmaceutical compositions are described. Methods of manufacturing the pharmaceutical compositions are described.

The present disclosure relates to multifunctional molecules comprising masked interleukin 12 and methods of making and using the same. In certain embodiments, the multifunctional molecules disclosed herein comprise a cleavable linker.

Monovalent IL-12 heterodimeric Fc proteins that display attenuated potency at the IL-12 receptor compared to wild-type IL-12 and have an extended half-life compared to wild-type IL-12 are described. The monovalent heterodimeric IL-12 heterodimeric Fc proteins comprise a heterodimer comprising an IL-12p35 subunit first Fc domain fusion protein and an IL-p40 subunit second Fc domain fusion protein IL-12 and Fc domains wherein the first and second Fc domains comprise modifications that facilitate heterodimerization of the first Fc domain to the second Fc domain.

The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to be a threat to global public health. While some individuals exhibit mild symptoms, others develop severe disease leading to severe lymphopenia and death. Provided herein are methods for determining whether a subject suffering from a SARS-Cov-2 infection is more likely to suffer from severe or mild disease. Also provided are methods for predicting whether a subject suffering from a SARS-Cov-2 infection with mild disease will progress to more severe disease and methods for treating patients having an infection via SARS-Cov-2 and related family members.

The present invention discloses a preparation method and application of transplanted tumor tissues, belonging to the field of biotechnology. Also disclosed is a reagent combination for preparing transplanted tumor tissues, including PMA and interleukins, wherein the interleukins include interleukin 2, interleukin 10 and interleukin 12. By using the reagent combination, kit and method of the present invention to prepare transplanted tumor tissues and further prepare quality control products, complex operations are not required, nor are a large number of consumables, culture equipment and culture space needed, which is very convenient for large-scale production; the transplanted tumor tissues of the present invention not only have stable sources and properties, but also the transplanted tumors have tissue-like morphology. When prepared into quality control products, they can provide more information in pathological interpretation. They can not only be used to monitor the process of immunohistochemistry experiments, but also assist in interpreting pathological results, and have very important clinical application value.

Provided is a cytokine combination useful for treating a tumor and / or preventing recurrence or metastasis of the tumor. The cytokine combination with at least three cytokines selected from the following groups: interleukin 12 (IL12) or a functional variant thereof, granulocyte-macrophage colony-stimulating factor (GMCSF) or a functional variant thereof, FMS-like tyrosine kinase 3 ligand (FLT3L) or a functional variant thereof, interleukin 2 (IL2) or a functional variant thereof, interleukin 15 (IL15) or a functional variant thereof, interleukin 21 (IL21) or a functional variant thereof, and interleukin 7 (IL7) or a functional variant thereof. Also provided is a nucleic acid molecule encoding the cytokine combination and a vector thereof, a cell, a pharmaceutical composition, and a application thereof for the manufacture of a drug for treating the tumor and / or preventing recurrence or metastasis of the tumor.

The invention discloses a nucleic acid molecule delivery carrier as well as a preparation method and application of a freeze-drying preparation of the nucleic acid molecule delivery carrier. Wherein the delivery vehicle comprises a nucleic acid molecule encoding interleukin 12 and an ionizable lipid compound. According to the invention, the mRNA of the interleukin 12 with an optimized sequence is used, the mRNA is more stable, the protein expression is increased, and the misfolding rate is reduced. Meanwhile, the interleukin 12 is anchored through a transmembrane sequence, so that the possible immune storm risk is reduced. Besides, on the basis of newly synthesized, degradable and novel ionizable lipid molecules, a high-efficiency and low-toxicity freeze-drying preparation delivery system based on lipid is formed, and the freeze-drying preparation has potential application value in the fields of preventive vaccines and therapeutic drugs.

The invention discloses an interleukin 12 mutant and application thereof, and belongs to the technical field of gene engineering. An IL-12 mutant protein comprises a mutated P40 subunit and / or a mutated P35 subunit wherein the mutated P40 subunit is obtained by mutating a wild-type P40 subunit at the following positions: position 37, 38, 39, 40, 81, 82, 106, 108, 114, 115 or / and 219, said mutation having a mutation that eliminates or reduces the binding affinity of the wild-type P40 subunit to IL-12R [beta] 1; wherein the mutated P35 subunit is obtained by mutating the wild-type P35 subunit at the following positions: the 72,151st or / and 190th position, and the mutation eliminates or reduces the mutation of binding affinity to IL-12R beta 2. The IL12 mutant protein and the fusion protein can significantly improve the treatment effect by reducing toxicity and enhancing tumor targeting.

The invention provides novel fusion proteins of Interleukin 12 and prodrugs, and compositions and methods of preparation thereof, useful in treating various diseases and disorders (e.g., hyperplasia, solid tumor or hematopoietic malignancy).

Disclosed are an interleukin 12 mutant and the use thereof, belonging to the technical field of genetic engineering. The IL-12 mutant protein comprises a mutated P40 subunit and / or a mutated P35 subunit, wherein the mutated P40 subunit is generated by means of mutating a wild-type P40 subunit at the following positions: positions 37, 38, 39, 40, 81, 82, 106, 108, 114, 115 or / and 219, and the mutation eliminates or reduces the binding affinity of the wild-type P40 subunit for IL-12Rβ1; and the mutated P35 subunit is generated by means of mutating a wild-type P35 subunit at the following positions: positions 72, 151 or / and 190, and the mutation eliminates or reduces the binding affinity for IL-12Rβ2. The IL12 mutant protein and fusion protein can significantly improve a therapeutic effect by means of reducing toxicity and enhancing tumor targeting.

The present disclosure provides surprisingly useful fusion polypeptides including an immunomodulatory moiety and a metal-hydroxide binding moiety, as well as various related technologies, including methods of making and of using such fusion polypeptides.

The present invention addresses the problem of providing an immune cell induced from an iPS cell, which imparts a phenotype that facilitates local migration and infiltration into a solid tumor and proliferation and survival of the immune cell in the solid tumor. [Solution] A cell which is an immune cell induced from an iPS cell and which expresses interleukin 15 and a cell surface molecule that is reactive with a tumor-associated antigen. And a cell which is an immune cell induced from an iPS cell and which expresses a cell surface molecule that is reactive with a tumor-associated antigen and interleukin 12, interleukin 18, or interleukin 21.

The present invention relates to muteins of the α-subunit of human Interleukin 12 as well as to muteins of the human Interleukin 12 comprising said α-subunit (p35) and a β-subunit. Further, the present invention is directed to a cDNA or DNA nucleic acid molecule or mRNA nucleic acid molecule comprising a nucleotide sequence encoding said muteins according to the present invention, to an engineered cell or virus, a recombinant protein, a fusion-protein, an immune modulator, a pharmaceutical composition comprising any of the muteins according to the present invention. Further, the present invention related to the use of the mutein for the manufacture of a medicament for treating a disease in a mammal, the mutein of the present invention for use as a medicament, a method of treating an Interleukin 12-mediated disease in a mammal, and a method for producing the mutein according to the present invention.

This disclosure relates to a multifunctional molecule containing a shielding interleukin 12, and to methods for fabricating and using the same. In certain embodiments, the multifunctional molecule disclosed herein includes a cleavable linker.

The disclosure features fusion proteins that are conditionally active variants of IL-12. In one aspect, the full-length polypeptides of the invention have reduced or minimal cytokine-receptor activating activity even though they contain a functional cytokine polypeptide. Upon activation, e.g., by cleavage of a linker that joins a blocking moiety, e.g., a steric blocking polypeptide, in sequence to the active cytokine, the cytokine can bind its receptor and effect signaling.

The present invention relates to muteins of the α-subunit of human Interleukin 12 as well as to muteins of the human Interleukin 12 comprising said α-subunit (p35) and a β-subunit. Further, the present invention is directed to a cDNA or DNA nucleic acid molecule or mRNA nucleic acid molecule comprising a nucleotide sequence encoding said muteins according to the present invention, to an engineered cell or virus, a recombinant protein, a fusion-protein, an immune modulator, a pharmaceutical composition comprising any of the muteins according to the present invention. Further, the present invention related to the use of the mutein for the manufacture of a medicament for treating a disease in a mammal, the mutein of the present invention for use as a medicament, a method of treating an Interleukin 12-mediated disease in a mammal, and a method for producing the mutein according to the present invention.

To provide novel fusion proteins between interleukin 12 and a prodrug, useful in treating various diseases and disorders (e.g., hyperplasia, solid tumor or hematopoietic malignancy).SOLUTION: Provided is a fusion protein comprising: a first structural unit that is one or two subunits of IL12 selected from P35 and P40 subunits, where the first structural unit is located at the N terminus of the fusion protein; a second structural unit that is an antibody Fc fragment located at the C terminus of the fusion protein; and a first linker segment covalently linking the first structural unit and the second structural unit or covalently linking the two subunits of the first structural unit.SELECTED DRAWING: None

Provided herein is a recombinant oncolytic virus comprising an oncolytic virus genome comprising a nucleic acid encoding an IL-2 / IL-12 fusion protein. The fusion protein may be membrane-anchored. Also provided are cells expressing the recombinant oncolytic virus as well as method of using the recombinant oncolytic virus and cells described herein, for example for the treatment of cancer. In a preferred embodiment, the oncolytic virus is a vaccinia virus.

The present disclosure relates to a recombinant poxvirus that contains a heterologous nucleic acid sequence encoding interleukin 12 (IL-12) in its genome. Provided are a recombinant poxvirus, a method for producing a composition (e.g., a pharmaceutical composition) containing the recombinant poxvirus, a method for treating cancer using the recombinant poxvirus, and a kit containing the recombinant poxvirus.

Monovalent IL-12 heterodimeric Fc proteins that display attenuated potency at the IL-12 receptor compared to wild-type IL-12 and have an extended half-life compared to wild-type IL-12 are described. The monovalent heterodimeric IL-12 heterodimeric Fc proteins comprise a heterodimer comprising an IL-12p35 subunit first Fc domain fusion protein and an IL-p40 subunit second Fc domain fusion protein IL-12 and Fc domains wherein the first and second Fc domains comprise modifications that facilitate heterodimerization of the first Fc domain to the second Fc domain.

This disclosure relates to anti-IL12p35 (interleukin 12 subunit alpha) antibodies, antigen-binding fragments, and the uses thereof. In some embodiments, the anti-IL12p35 antibodies or antigen-binding fragments thereof described herein can be used for treating systemic sclerosis (SSc), primary biliary cholangitis (PBC), systemic lupus erythematosus (SLE), and / or Sjogren's syndrome (SjS).

The disclosure features fusion proteins that are conditionally active variants of IL-12. In one aspect, the full-length polypeptides of the invention have reduced or minimal cytokine-receptor activating activity even though they contain a functional cytokine polypeptide. Upon activation, e.g., by cleavage of a linker that joins a blocking moiety, e.g., a steric blocking polypeptide, in sequence to the active cytokine, the cytokine can bind its receptor and effect signaling.