842results about "Cytokines/lymphokines/interferons" patented technology

Methods for obtaining a protein by culture of hybridoma cells, wherein said protein is an immunoglobulin, are disclosed. The methods involve culturing animal hybridoma cells in continuous presence of an alkanoic acid or salt thereof, which enhances protein production, wherein said alkanoic acid or salt thereof is present at 2 concentration range of 0.1 mM to 200 mM.

The present invention includes the receptor protein 4-1BB and the cDNA gene encoding for receptor protein 4-1BB. The nucleotide sequence of the isolated cDNA is disclosed herein along with the deduced amino acid sequence. The 4-1BB protein and fragments and derivatives can be used: 1) as a probe to isolate ligands to receptor protein 4-1BB, 2) to stimulate proliferation of B-cell's expressing 4-1BB, or 3) to block 4-1BB ligand binding. A monoclonal antibody against 4-1BB was developed which specifically recognizes an epitope on the extracellular domain of receptor protein 4-1BB. The monoclonal antibody can be used enhance T-cell proliferation and activation by treating T-cells that have expressed receptor protein 4-1BB with the monoclonal antibody. The effectiveness of the treatment was enhanced when conducted in the presence of protein tyrosinase kinase. A fusion protein for detecting cell membrane ligands to receptor protein 4-1BB was developed. It comprises the extracellular portion of the receptor protein 4-1BB and a detection protein bound to the portion of the receptor protein 4-1BB.

Methods for the treatment of lymphoma by administration of a B cell-specific antibody are described. The invention encompasses providing to a patient both unlabeled antibodies and antibodies labeled with a radioisotope. A principal advantage of the method is that tumor responses can be obtained in a radiometric dose range that does not require hematopoietic stem cell replacement as an adjunct therapy also described is a composition useful in the treatment of lymphoma.

This invention relates to novel pharmaceutically useful compositions that bind to a biological molecule, having improved circulatory half-life, increased avidity, increased affinity, or multifunctionality, and methods of use thereof. The present invention provides a pseudo-antibody comprising an organic moiety covalenty coupled to at least two target-binding moieties, wherein the target-binding moieties are selected from the group consisting of a protein, a peptide, a peptidomimetic, and a non-peptide molecule that binds to a specific targeted biological molecule. The pseudo-antibody of the present invention may affect a specific ligand in vitro, in situ and / or in vivo. The pseudo-antibodies of the present invention can be used to measure or effect in an cell, tissue, organ or animal (including humans), to diagnose, monitor, modulate, treat, alleviate, help prevent the incidence of, or reduce the symptoms of, at least one condition.

The present invention relates to a peptide-based compound comprising a peptide moiety and a poly(ethylene glycol) moiety wherein the poly(ethylene glycol) moiety (preferably linear) has a molecular weight of more than 20 KDaltons (preferably from 20 to 60 KDaltons). The peptide moiety may be monomeric, dimeric or oligomeric. Such peptide-based compounds may optional include a linker moiety and / or a spacer moiety.

An expression system which provides heterologous proteins expressed by a non-native host organism but which have native-protein-like biological activity and / or structure. Disclosed are vectors, expression hosts and methods for expressing the heterologous proteins. The expression system involves co-expression of protein factor(s) which is / are capable of catalyzing disulphide bond formation and desired heterologous protein(s). The expression system is presented using yeast cells as the preferred host, protein disulphide isomerase (PDI) and thioredoxin (TRX) as the preferred examples of the protein factors and HCV-E2715 envelope glycoprotein and human FIGF as the preferred examples of the heterologous proteins.

Disclosed herein are methods and compositions for enhancing the immunogenicity of a preselected protein or peptide antigen in a mammal. Immunogenicity is enhanced by fusing the preselected antigen to an immunoglobulin heavy chain constant region to produce an Fc-antigen fusion protein. The Fc-antigen fusion proteins bind Fc receptors on the surface of antigen presenting cells, thereby targeting the antigen to the antigen presenting cells in the mammal. In addition, disclosed is a family of adjuvants, for example, an Fc-adjuvant fusion protein, for use in combination with the Fc-antigen fusion proteins to enhance or modulate a particular immune response against the preselected antigen.

The invention provides cytokine fusion proteins with an increased therapeutic index, and methods to increase the therapeutic index of such fusion proteins. The fusion proteins of the invention are able to bind to more than one type of cytokine receptor expressed on cells and also bind to more than one cell type. In addition, the fusion proteins of the invention exhibit a longer circulating half-life in a patient's body than the corresponding naturally occurring cytokine.

Nucleic acid sequences containing unmethylated CpG dinucleotides that modulate an immune response including stimulating a Th1 pattern of immune activation, cytokine production, NK lytic activity, and B cell proliferation are disclosed. The sequences are also useful as a synthetic adjuvant.

A cell penetrating peptide which has following sequence: NYBX1BX2BNQX3, wherein B represents a basic amino acid, X1 represents an amino acid with an aromatic, a hydrophobic or an uncharged side chain, X2 represents any amino acid, and X3 represents N or none is described. A method for delivering a cargo into a subject by administrating a complex comprising the cell penetrating peptide and the desired cargo to the subject is also described.

Oligonucleotides are provided which are effective in inhibiting the growth, metastasis and / or angiogenesis of tumors, including particularly melanoma and / or lung cancer. Methods are also provided for use of these oligonucleotides in the treatment of diseases.

A method for identifying and isolating cells which produce secreted proteins. This method is based upon a specific characteristic or the expression level of the secreted protein by transiently capturing the secreted protein on the surface of an individual cell, allowing selection of rare cell clones from a heterogeneous population. Also provided is the use of this method to generate cells which produce a desired level of secreted protein or secreted protein of a particular characteristic(s), and organisms which possess such cells. In particular, the method allows rapid isolation of high expression recombinant antibody-producing cell lines, or may be applied directly to rapid isolation of specific hybridomas, or to the isolation of antibody-producing transgenic animals. This method is applicable for any cell which secretes protein.

Methods and compositions are provided for protecting or enhancing a responsive cell, tissue, organ or body part function or viability in vivo, in situ or ex vivo in mammals, including human beings, by systemic or local administration of an erythropoietin receptor activity modulator, such as an recombinant tissue protective cytokine.

The present invention concerns methods and compositions for forming cytokine-antibody complexes using dock-and-lock technology. In preferred embodiments, the cytokine-MAb DNL complex comprises an IgG antibody attached to two AD (anchor domain) moieties and four cytokines, each attached to a DDD (docking and dimerization domain) moiety. The DDD moieties form dimers that bind to the AD moieties, resulting in a 2:1 ratio of DDD to AD. The cytokine-MAb complex exhibits improved pharmacokinetics, with a significantly longer serum half-life than either naked cytokine or PEGylated cytokine. The cytokine-MAb complex also exhibits significantly improved in vitro and in vivo efficacy compared to cytokine alone, antibody alone, unconjugated cytokine plus antibody or cytokine-MAb DNL complexes incorporating an irrelevant antibody. In a most preferred embodiment the complex comprises an anti-CD20 IgG antibody conjugated to four IFN-α2b moieties, although other antibodies and cytokines have been used to form effect DNL complexes.

Gene delivery vectors, such as, for example, recombinant adeno-associated viral vectors, and methods of using such vectors are provided for use in treating or preventing diseases of the eye.

The invention relates to methods of treating a blood disorder in a mammal with an interleukin-1 (IL-1) inhibitor. The invention also relates to methods of treating a blood disorder in a mammal with an IL-1 inhibitor, a TNF inhibitor and an erythropoietin (EPO) receptor agonist. The invention also relates to compositions of an IL-1 inhibitor and compositions of an IL-1 inhibitor, a TNF inhibitor and an EPO receptor agonist.

Targeted therapeutics that localize to a specific subcellular compartment such as the lysosome are provided. The targeted therapeutics include a therapeutic agent and a targeting moiety that binds a receptor on an exterior surface of the cell, permitting proper subcellular localization of the targeted therapeutic upon internalization of the receptor. Nucleic acids, cells, and methods relating to the practice of the invention are also provided.

Pharmaceutical formulations and methods are provided for the sustained delivery of a pharmaceutical agent to a patient by injection, by oral administration or by topical administration. The injectable formulation includes porous microparticles which comprise a pharmaceutical agent and a matrix material, wherein upon injection of the formulation a therapeutically or prophylactically effective amount of the pharmaceutical agent is released from the microparticles for at least 24 hours. The oral formulation includes porous microparticles which comprise a pharmaceutical agent and a matrix material, wherein a therapeutically or prophylactically effective amount of the pharmaceutical agent is released from the microparticles for at least 2 hours following oral administration. The topical formulation includes porous microparticles which comprise a pharmaceutical agent and a matrix material, wherein a therapeutically or prophylactically effective amount of the pharmaceutical agent is released from the microparticles for at least 2 hours following topical administration.

The present invention relates to compositions and methods for inhibiting the release and / or biological activity of migration inhibitory factor (MIF). In particular, the invention relates to the uses of such compositions and methods for the treatment of various conditions involving cytokine-mediated toxicity, which include, but are not limited to shock, inflammation, graft versus host disease, and / or autoimmune diseases.

The present invention relates to methods and compositions for the treatment and diagnosis of immune disorders, especially T helper lymphocyte-related disorders. In particular, the invention provides a nucleotide sequence which encodes a previously unknown human 103 gene product. The invention also provides expression vectors containing the nucleic acid molecules of the invention and host cells into which the expression vectors have been introduced. The invention still further provides isolated polypeptides, fusion polypeptides, antigenic peptides and antibodies.

Nucleic acid sequences containing unmethylated CpG dinucleotides that modulate an immune response including stimulating a Th1 pattern of immune activation, cytokine production, NK lytic activity, and B cell proliferation are disclosed. The sequences are also useful as a synthetic adjuvant.

The present invention encompasses assays to identify compounds that inhibit the enzymatic activity of MIF which catalyzes the tautomerization of MIF-substrates, such as D-dopachrome to DHICA. In general, the assay is conducted in vitro by adding, mixing or combining MIF and a suitable substrate in the presence or absence of a test compound, and measuring the tautomerization of the substrate. The test compounds that inhibit tautomerization in the assay are identified as MIF inhibitors.

The present invention relates to a counter-receptor, termed CD40CR, for the CD40 B-cell antigen, and to soluble ligands for this receptor, including fusion molecules comprising at least a portion of CD40 protein. It is based, at least in part, on the discovery that a soluble CD40 / immunoglobulin fusion protein or antibody specific for gp39 on T cells was able to inhibit helper T-cell mediated B-cell activation by binding to a novel 39 kD protein receptor on helper T-cell membranes. The present invention provides for a substantially purified CD40CR receptor; for soluble ligands of CD40CR, including antibodies as well as fusion molecules comprising at least a portion of CD40 protein; and for methods of controlling B-cell activation which may be especially useful in the treatment of allergy or autoimmune disease, including graft-versus-host disease and rheumatoid arthritis.

The present invention relates to methods and compositions for modifying peptides, polypeptides and proteins with polymers, especially glyco-mimetic polymers, so as to improve their biological activity or pharmacokinetic properties. The invention further provides methods and uses for such polymer-modified peptides, polypeptides and proteins. The invention is particularly suitable for use in the synthesis of polymer-modified synthetic bioactive proteins (FIG. 1D), and of pharmaceutical compositions that contain such proteins.

This invention provides novel methods of obtaining autologous monoclonal antibodies (AMABs) to self-antigens or homologs thereof. The method involves obtaining a genetically engineered host animal that does not biosynthesize at least one epitope of the antigen and utilizes the lack of self-tolerance of the host to the epitope to produce antibodies specific to the antigen. The invention also encompasses the AMABs produced by the methods. The invention further encompasses methods of isolating cells comprising the use of such AMABs that have specificity for a cell surface antigen.

A conjugate is disclosed herein, wherein the conjugate includes a ligand having the ability to specifically and stably bind to an external receptor or binding site on a tumor vasculature endothelial cell, wherein the external receptor or binding site is specific for tumor vasculature endothelial cells. The conjugate also includes an anticancer agent that is selectively toxic to cancer cells operatively attached to the ligand. The anticancer agent may be L-methioninase. Pharmaceutical compositions comprising the conjugate are also disclosed, as well as methods of treating a cancer tumor or cancer cells with a therapeutically effective amount of the conjugate.

The present invention is directed towards classifying tumor biomarkers, particularly membrane receptors, and more particularly the gastrin-releasing peptide (GPR) receptors, identified in patient samples, then linking therapeutic agents (chemical, radiological, or biological) to patient-specific ligands that bind to such receptors, clinicians can produce diagnostic and treatment compositions and implement treatment regimens which, by using the classified and identified biomarkers, and due to their improved accuracy, increase success and decrease undesired side effects from such treatments.

The present invention relates to a novel Neutrokine-alpha protein which is a member of the TNF protein family. In particular, isolated nucleic acid molecules are provided encoding the human Neutrokine-alpha protein including soluble forms of the extracellular domain. Neutrokine-alpha polypeptides are also provided as are vectors, host cells and recombinant methods for producing the same. The invention further relates to screening methods for identifying agonists and antagonists of Neutrokine-alpha activity. Also provided are diagnostic methods for detecting immune system-related disorders and therapeutic methods for treating immune system-related disorders.