62 results about "Interferon receptor" patented technology

The present inventors succeeded in separating bispecific antibodies that functionally substitute for ligands of type I interferon receptors comprising two types of molecules: AR1 chain and AR2 chain. Furthermore, the present inventors succeeded in producing bispecific antibodies that substitute for the enzyme reaction-accelerating function of blood coagulation factor VIII / activated blood coagulation factor VIII, which bind to both blood coagulation factor IX / activated blood coagulation factor IX and blood coagulation factor X.

This invention provides methods to prepare and use immunostimulatory cells for enhancing an immune response. The invention provides a method for preparing mature dendritic cells (DCs), comprising the sequential steps of: (a) signaling isolated immature dendritic cells (iDCs) with a first signal comprising an interferon gamma receptor (IFN-γR) agonist and / or a tumor necrosis factor alpha receptor (TNF-αR) agonist to produce signaled dendritic cells; and (b) signaling said signaled dendritic cells with a second transient signal comprising an effective amount of a CD40 agonist to produce CCR7+ mature dendritic cells. Also provided by this invention are enriched populations of dendritic cells prepared by the methods of the invention. Such dendritic cells have enhanced immunostimulatory properties and increased IL-12 secretion and / or decreased IL-10 secretion. CD40 signaling can be initiated by one or more of polypeptide translated from an exogenous polynucleotide encoding CD40L (e.g., mRNA or DNA), an agonistic antibody to CD40 receptor or by CD40 ligand polypeptide. The enriched populations can be further modified by the administration of an immunogen to the DC. The DC will take up and process the immunogen on its cell surface.

This invention provides methods to prepare and use immunostimulatory cells for enhancing an immune response. The invention provides a method for preparing mature dendritic cells (DCs), comprising the sequential steps of: (a) signaling isolated immature dendritic cells (iDCs) with a first signal comprising an interferon gamma receptor (IFN-γR) agonist and / or a tumor necrosis factor alpha receptor (TNF-αR) agonist to produce signaled dendritic cells; and (b) signaling said signaled dendritic cells with a second transient signal comprising an effective amount of a CD40 agonist to produce CCR7+ mature dendritic cells. Also provided by this invention are enriched populations of dendritic cells prepared by the methods of the invention. Such dendritic cells have enhanced immunostimulatory properties and increased IL-12 secretion and / or decreased IL-10 secretion. CD40 signaling can be initiated by one or more of polypeptide translated from an exogenous polynucleotide encoding CD40L (e.g., mRNA or DNA), an agonistic antibody to CD40 receptor or by CD40 ligand polypeptide. The enriched populations can be further modified by the administration of an immunogen to the DC. The DC will take up and process the immunogen on its cell surface.

The present invention provides isolated human monoclonal antibodies that bind to IFNAR-1 and that are capable of inhibiting the biological activity of Type I interferons. Immunoconjugates, bispecific molecules and pharmaceutical compositions comprising the antibodies of the invention are also provided. The invention also provides methods for inhibiting Type I interferon-mediated disorders using the antibodies of the invention, including methods for treating autoimmune disorders, transplant rejection or Graft Versus Host Disease using the antibodies of the invention.

The present invention provides synthetic Type I interferon receptor polypeptide agonists comprising consensus or hybrid Type I interferon receptor polypeptide agonists, containing one or more native or non-native glycosylation sites. The present invention provides synthetic Type I interferon receptor polypeptide agonists comprising consensus or hybrid Type I interferon receptor polypeptide agonists, containing one or more native or non-native glycosylation sites, as well as erythropoietin and darbepoetin alfa, each of which are linked to a penetrating peptide that facilitates translocation of a substance across a biological barrier as well as pharmaceutical compositions, including oral formulations, of the same. The present invention further provides oral formulations of hyperglycosylated or protease-resistant, hyperglycosylated polypeptide variants, which polypeptide variants lack at least one protease cleavage site found in a parent polypeptide, and thus exhibit increased protease resistance compared to the parent polypeptide, which polypeptide variants further include (1) a carbohydrate moiety covalently linked to at least one non-native glycosylation site not found in the parent protein therapeutic or (2) a carbohydrate moiety covalently linked to at least one native glycosylation site found but not glycosylated in the parent protein therapeutic. The present invention further provides compositions, including oral pharmaceutical compositions, comprising the synthetic Type I interferon receptor polypeptide agonist, the hyperglycosylated polypeptide variant, or the hyperglycosylated, protease-resistant polypeptide variant. The present invention further provides containers, devices, and kits comprising the synthetic Type I interferon receptor polypeptide agonist, the hyperglycosylated polypeptide variant, or the hyperglycosylated, protease-resistant polypeptide variant. The present invention further provides therapeutic methods involving administering an effective amount of an oral pharmaceutical composition comprising a synthetic Type I interferon receptor polypeptide agonist, a hyperglycosylated polypeptide variant, or a hyperglycosylated, protease-resistant polypeptide variant to an individual in need thereof.

Disclosed in certain embodiments is a method of preparing a Type 1 interferon antagonist comprising modifying a Type 1 interferon at the site of interaction with the interferon receptor subunit IFNAR-1 such that the binding affinity of the interferon to the IFNAR-1 subunit is reduced as compared to the native interferon, and corresponding compositions and methods of treatment thereof.

The present invention provides methods for treating alphavirus infections; methods of treating hepatitis C virus (HCV) infections; methods of treating West Nile virus infection; methods of reducing liver fibrosis; methods of increasing liver function in an individual suffering from liver fibrosis; methods of reducing the incidence of complications associated with HCV and cirrhosis of the liver; and methods of reducing viral load, or reducing the time to viral clearance, or reducing morbidity or mortality in the clinical outcomes, in patients suffering from viral infection. The methods generally involve administering effective amounts of an interferon receptor agonist and pirfenidone in combination therapy.

The present invention provides synthetic Type I interferon receptor polypeptide agonists comprising consensus or hybrid Type I interferon receptor polypeptide agonists, containing one or more native or non-native glycosylation sites. The present invention further provides oral formulations of protease-resistant or protease-resistant, hyperglycosylated polypeptide variants, which polypeptide variants lack at least one protease cleavage site found in a parent polypeptide, and thus exhibit increased protease resistance compared to the parent polypeptide, which polypeptide variants further include (1) a carbohydrate moiety covalently linked to at least one non-native glycosylation site not found in the parent protein therapeutic or (2) a carbohydrate moiety covalently linked to at least one native glycosylation site found but not glycosylated in the parent protein therapeutic. The present invention further provides compositions, including oral pharmaceutical compositions, comprising the synthetic Type I interferon receptor polypeptide agonist, the hyperglycosylated polypeptide variant, the protease-resistant polypeptide variant, or the hyperglycosylated, protease-resistant polypeptide variant. The present invention further provides containers, devices, and kits comprising the synthetic Type I interferon receptor polypeptide agonist, the hyperglycosylated polypeptide variant, the protease-resistant polypeptide variant, or the hyperglycosylated, protease-resistant polypeptide variant. The present invention further provides therapeutic methods involving administering an effective amount of an oral pharmaceutical composition comprising a synthetic Type I interferon receptor polypeptide agonist, a hyperglycosylated polypeptide variant, a protease-resistant polypeptide variant, or a hyperglycosylated, protease-resistant polypeptide variant to an individual in need thereof.

The present invention provides synthetic Type I interferon receptor polypeptide agonists comprising consensus or hybrid Type I interferon receptor polypeptide agonists, containing one or more native or non-native glycosylation sites. The present invention provides synthetic Type I interferon receptor polypeptide agonists comprising consensus or hybrid Type I interferon receptor polypeptide agonists, containing one or more native or non-native glycosylation sites, as well as erythropoietin and darbepoetin alfa, each of which are linked to a penetrating peptide that facilitates translocation of a substance across a biological barrier as well as pharmaceutical compositions, including oral formulations, of the same. The present invention further provides oral formulations of hyperglycosylated or protease-resistant, hyperglycosylated polypeptide variants, which polypeptide variants lack at least one protease cleavage site found in a parent polypeptide, and thus exhibit increased protease resistance compared to the parent polypeptide, which polypeptide variants further include (1) a carbohydrate moiety covalently linked to at least one non-native glycosylation site not found in the parent protein therapeutic or (2) a carbohydrate moiety covalently linked to at least one native glycosylation site found but not glycosylated in the parent protein therapeutic. The present invention further provides compositions, including oral pharmaceutical compositions, comprising the synthetic Type I interferon receptor polypeptide agonist, the hyperglycosylated polypeptide variant, or the hyperglycosylated, protease-resistant polypeptide variant. The present invention further provides containers, devices, and kits comprising the synthetic Type I interferon receptor polypeptide agonist, the hyperglycosylated polypeptide variant, or the hyperglycosylated, protease-resistant polypeptide variant. The present invention further provides therapeutic methods involving administering an effective amount of an oral pharmaceutical composition comprising a synthetic Type I interferon receptor polypeptide agonist, a hyperglycosylated polypeptide variant, or a hyperglycosylated, protease-resistant polypeptide variant to an individual in need thereof.

The in vivo effect of Type I interferon (IFN) can be prolonged by administering the interferon in the form of a complex with an IFN binding chain of the human interferon alpha / beta receptor (IFNAR). Such a complex also improves the stability of the IFN and enhances the potency of the IFN. The complex may be a non-covalent complex or one in which the IFN and the IFNAR are bound by a covalent bond or a peptide. When bound by a peptide bond in the form of a fusion protein, the IFN may be separated from the IFNAR by means of a peptide linker. Such a fusion protein may be produced by recombinant DNA technology. Storing IFN in the form of such a complex improves the storage life of the IFN and permits storage under milder conditions than would otherwise be possible.

Compositions and methods for the therapy of Inflammatory Bowel Disease (IBD), including Celiac Disease, Crohn's Disease, and Ulcerative Colitis, are disclosed. Illustrative compositions comprise one or more anti-type 1 interferon antagonists, such as anti-type 1 interferon receptor antibody antagonists and fragments thereof, as well as polypeptides and small molecules that inhibit the interaction of type 1 interferon with its receptor (IFNAR).

The present invention relates to mutant polypeptides of the beta chain of the type I interferon receptor (MIFNAR2) with enhanced affinity for interferon-beta, which prolong the in vivo action of IFN-beta compared to the wild-type protein.

The present invention provides methods of treating hepatitis C virus (HCV) infection; methods of reducing the incidence of complications associated with HCV and cirrhosis of the liver; and methods of reducing viral load, or reducing the time to viral clearance, or reducing morbidity or mortality in the clinical outcomes, in patients suffering from HCV infection. The methods generally involve administering to the individual i) a Type I interferon receptor agonist or a Type III interferon receptor agonist; ii) an immunomodulatory agent; and iii) an inhibitor of an HCV enzyme.

The invention discloses a preparation method of an anti-human IFNAR1 monoclonal antibody concentrated solution, which comprises the following steps: first ultrafiltration concentration: concentrating a solution containing an anti-human interferon alpha receptor 1 (IFNAR1) monoclonal antibody until the protein concentration is 20-60mg / ml under the conditions that the flow rate is 120-300L / m<2>.h and the transmembrane differential pressure (TMP) is 0.6-1.5 bar, so as to obtain a concentrated sample; ultrafiltration replacement: replacing the concentrated sample with a replacement buffer solution, and obtaining an ultrafiltration replacement solution when the usage amount of the replacement buffer solution is 6-10 times of the weight of the concentrated sample; and second ultrafiltration concentration: uniformly mixing the ultrafiltration replacement solution and the alkaline amino acid mother liquor to enable the concentration of amino acid to be 100-150mM, and performing ultrafiltration concentration to obtain a concentrated solution with the protein concentration of 100-200mg / ml. According to the preparation method, the viscosity of the high-concentration antibody liquid medicine can be reduced, the stability can be improved, the method is simple and easy to implement, large-scale production can be carried out, the high purity of a sample can be guaranteed, and the high recovery rate can be obtained.

The present invention provides synthetic Type I interferon receptor polypeptide agonists comprising consensus or hybrid Type I interferon receptor polypeptide agonists, containing one or more native or non-native glycosylation sites. The present invention further provides oral formulations of protease-resistant or protease-resistant, hyperglycosylated polypeptide variants, which polypeptide variants lack at least one protease cleavage site found in a parent polypeptide, and thus exhibit increased protease resistance compared to the parent polypeptide, which polypeptide variants further include (1) a carbohydrate moiety covalently linked to at least one non-native glycosylation site not found in the parent protein therapeutic or (2) a carbohydrate moiety covalently linked to at least one native glycosylation site found but not glycosylated in the parent protein therapeutic. The present invention further provides compositions, including oral pharmaceutical compositions, comprising the synthetic Type I interferon receptor polypeptide agonist, the hyperglycosylated polypeptide variant, the protease-resistant polypeptide variant, or the hyperglycosylated, protease-resistant polypeptide variant. The present invention further provides containers, devices, and kits comprising the synthetic Type I interferon receptor polypeptide agonist, the hyperglycosylated polypeptide variant, the protease-resistant polypeptide variant, or the hyperglycosylated, protease-resistant polypeptide variant. The present invention further provides therapeutic methods involving administering an effective amount of an oral pharmaceutical composition comprising a synthetic Type I interferon receptor polypeptide agonist, a hyperglycosylated polypeptide variant, a protease-resistant polypeptide variant, or a hyperglycosylated, protease-resistant polypeptide variant to an individual in need thereof.

The invention belongs to the technical field of medicine and bioengineering, and relates to application of a human interferon alpha receptor binding related site mutant in preparation of an anti-hepatitis B virus preparation. The interferon alpha plays an antiviral role through a receptor compound combined by two subunits of I-type interferon receptors IFNAR1 and IFNAR2. According to the invention, mutation is carried out on a site where IFN-alpha2 is combined with IFNAR1, and prokaryotic purification expression is carried out in vitro; the recognition in an HBV infection model shows that thehuman interferon alpha receptor binding related site mutant IFN-alpha2-EIFK has stronger anti-hepatitis B virus activity than IFN-alpha2, and has no cytotoxic effect under the antiviral concentration.The IFN-alpha2 receptor disclosed by the invention is combined with a related site mutant, namely IFN-alpha2-EIFK, so that a novel anti-hepatitis B virus medicine can be further prepared.

The present disclosure relates to identification of previously known genes as being genes upregulated by interferon-α administration, in particular the human genes corresponding to the cDNA sequence in GenBank designated g4758303, g5453897, g4505186, g2366751, g33917, g4504962, g3978516, g5924396, g4505656, g1504007, g3702446, g4001802, g292289, g4557226, g4507646 and g4507170. Determination of expression products of these genes is proposed as having utility in predicting responsiveness to treatment with interferon-α and other interferons which act at the Type 1 interferon receptor.

The invention relates to the technical field of biological medicines, and provides an amino acid sequence of a chikungunya virus (CHIKV) E2 protein rabbit monoclonal antibody and application thereof. The amino acid sequence of the CHIKV E2 protein rabbit monoclonal antibody comprises an amino acid sequence of a heavy chain and an amino acid sequence of a light chain of the antibody. The antibody expressed by mammalian cells can neutralize infection of CHIKV genotypes which are mainly popular in the world on the cells in vitro, and can protect type I interferon receptor genes from knocking out mice to resist fatal CHIKV infection in vivo. The antibody is modified, such as humanized modification or preparation of a single-chain antibody, and is expected to be used for treating severe CHIKV infection.

Antisense compounds, compositions and methods are provided for modulating the expression of Interferon gamma receptor 2. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding Interferon gamma receptor 2. Methods of using these compounds for modulation of Interferon gamma receptor 2 expression and for treatment of diseases associated with expression of Interferon gamma receptor 2 are provided.

A method of detecting genes which comprises detecting gene polymorphisms in allergy-predisposition-related genes; i.e., interleukin 12 receptor IL-1 β2 chain and β1 chain genes, interleukin 18 receptor α chain gene, interferon γ receptor 1 chain gene and interleukin 12.p40 subunit gene, to thereby detect allergic predisposition. Use of the present method enables contribution to the prevention of onset of allergic diseases and to the treatment of allergic diseases.

The invention provides a polymorphism sign found in an area of interferon receptor gene, which can be used for evaluating the curative effect of the interferon. Therefore, the invention also relates to the method for evaluating the personal curative effect of interferon and the device for finishing the method.

The invention relates to a mumps virus attacking animal model and an establishment method thereof, and belongs to the technical field of biology. The invention provides a mumps virus counteracting animal model. The mumps virus counteracting animal model is an interferon receptor deletion animal which is intravenously injected with mumps virus. Research finds that compared with common mice, the mumps virus load in blood of the interferon receptor-deleted mice is remarkably improved after the mumps virus is attacked by the interferon receptor-deleted mice, and compared with intramuscular injection and intranasal injection, the mumps virus load in blood of the interferon receptor-deleted mice is remarkably improved after the mumps virus is injected into the interferon receptor-deleted mice through caudal veins, so that the mumps virus load in blood of the interferon receptor-deleted mice is remarkably improved. Intravenous injection of the mumps virus to the interferon receptor-deficient animal can break through species limitation, effective infection of the mumps virus in the animal body is realized, and symptoms similar to human infection (for example, remarkable replication in various visceral organs) are formed, so that the mumps virus challenge animal model can be used as the mumps virus challenge animal model.

The invention relates to an anti-human interferon alpha receptor 1 (IFNAR1) monoclonal antibody and application thereof. The anti-human interferon alpha receptor 1 (IFNAR1) monoclonal antibody comprises three heavy chain complementary determining regions (CDR-H1, CDR-H2 and CDR-H3) and three light chain complementary determining regions (CDR-L1, CDR-L2 and CDR-L3). Wherein (a) the amino acid sequence of the CDR-H1 is as shown in SEQ ID NO: 1, (b) the amino acid sequence of CDR-H2 is as shown in SEQ ID NO: 2; (c) the amino acid sequence of the CDR-H3 is as shown in SEQ ID NO: 3; (d) the amino acid sequence of the CDR-L1 is as shown in SEQ ID NO: 4; (e) the amino acid sequence of the CDR-L2 is as shown in SEQ ID NO: 5; and (f) the amino acid sequence of the CDR-L3 is as shown in SEQ ID NO: 6. The affinity of the anti human interferon alpha receptor 1 (IFNAR1) monoclonal antibody for binding human IFNAR1 is equivalent to that of the anti human IFNAR1 monoclonal antibody Anifrolumab, the neutralizing activity of the anti-human IFNAR1 monoclonal antibody for binding with the human IFNAR1 monoclonal antibody at the cellular level is equivalent to that of the Anifrolumab, and the anti-human IFNAR1 monoclonal antibody is expected to show a good clinical effect in the aspect of preventing and treating related diseases.

The invention relates to a human interferon kappa (hIFNkappa) mutant and a preparation method thereof. The hIFN-kappa variant is obtained by mutating free cysteine (C) at the 166th site of an amino acid sequence shown as SEQ ID NO.1 of hIFN-kappa into serine (S) or mutating into glycine (G) or alanine (A) with a structure similar to that of serine. Compared with a strain containing a wild type hIFN-kappa sequence, the hIFN-kappa produced by expression of the plasmid strain containing the mutant sequence is relatively high in yield, higher in affinity of binding with an interferon-kappa receptor and better in in-vitro activity.

The invention discloses an affinity purification method for lowering protein content of a host cell in monoclonal antibody production. The method comprises the following steps: balancing an affinity chromatography medium by using a first balance buffer solution to obtain a balanced affinity chromatography medium, and combining monoclonal antibody fermentation liquor with the balanced affinity chromatography medium; and then, carrying out intermediate pre-elution leaching, and then, carrying out final elution to remove host-cell proteins so as to obtain a monoclonal antibody. The monoclonal antibody is a separated monoclonal antibody against a human interferon alpha receptor 1 (IFNAR1), and comprises three heavy-chain complementary determining regions (CDR-H1, CDR-H2 and CDR-H3) and three light-chain complementary determining regions (CDR-L1, CDR-L2 and CDR-L3). The method is simple and easy to implement, amplified purification production can be carried out, cell fermentation supernatant does not need pretreatment, the elution sample yield is relatively high, meanwhile, a HCP residual quantity is also kept at a relatively low level (the residual control quantity is not higher than 0.1%), and therefore, the pressure for removing HCP in a subsequent purification step is relieved.