Abstract: This invention provides a recombinant super-compound interferon or an equivalent thereof with changed spatial configuration. The super-compound interferon possesses anti-viral or anti-tumor activity and therefore is useful to prevent and treat viral diseases and cancers. This invention also provides an artificial gene which codes for the super-compound interferon or its equivalent. Finally, this invention provides methods to produce recombinant super-compound interferon or its equivalent and various uses of said interferon.

Abstract: The present invention provides compounds, compositions and methods that enhance the transfer of an agent into a cell. The agents can include polypeptides, polynucleotides such as genes and antisense nucleic acids, and other molecules. In some embodiments, the agents are modulating agents that can modulate a cellular activity or function when introduced into the cell. The compounds, compositions and methods are useful for introducing agents such as genes into individual cells, as well as cells that are present as a tissue or organ.

Abstract: The present invention relates to the IL-12p40 subunit mutant gene which can produce IL-12(interleukin 12) of human and mouse origin with high activity, the expression vector including above mutant gene and the use of them to DNA vaccine adjuvant. Particularly, it relates to IL-12p40 mutant gene which inhibits the secretion of IL-12p40 but normally secretes active IL-12p70 by making mutation at Asn-222(human) or Asn-220(mouse) amino acid of IL-12p40, which acts as a competitive inhibitor of active form of IL-12, IL-12p70. Therefore, the IL-12p40 mutant gene of the present invention can be useful for DNA vaccination and gene therapy against various diseases, for example, AIDS, hepatitis C or hepatitis B, cancer, influenza, tuberculosis and malaria, which essentially require cellular immune responses for their therapy.

Abstract: The present invention relates to polynucleotide and polypeptide molecules for Zcyto21, an interferon-like protein, which is most closely related to interferon-? at the amino acid sequence level. The present invention also includes antibodies to the Zcyto21 polypeptides, and methods of using the polynucleotides and polypeptides.

Abstract: The invention provides a method for treating a tumor in a human comprising administering to the tumor a dose of a pharmaceutical composition comprising (i) a pharmaceutically acceptable carrier and (ii) an adenoviral vector comprising a nucleic acid sequence encoding TNF-? operably linked to a promoter, wherein the dose comprises about 1×107 to about 4×1012 particle units (pu) of replication-deficient adenoviral vector, at least once in a therapeutic period comprising up to 10 weeks, whereby the tumor in human is treated.

Abstract: The present invention includes interferon-tau (IFN?) pharmaceutical compositions useful for oral administration to treat cancers, autoimmune disorders (particularly multiple sclerosis), cell proliferative disorders and viral disease.

Abstract: A nucleic acid formulation for use in gene delivery comprising a nucleic acid and an anionic polymer is disclosed. Examples of the anionic polymer includes aniionic amino acid polymer or poly-amino acid (such as poly-L-glutamic acid, poly-D-glutamic acid, poly-L-aspartic acid, poly-D-aspartic acid), poly-acrylic acid, polynucleotides, poly galacturonic acid, and poly vinyl sulfate.

Abstract: The present invention provides a method for providing latency to a pharmaceutically active agent. The method has application in overcoming the toxic effect of systemic administration of potent biological agents. The method comprises associating a fusion protein comprising a latency associated peptide and a proteolytic cleavage site with a pharmaceutically active agent. The fusion protein also has application in providing site specific activation to a latent pharmaceutically active agent.

Abstract: The present invention relates to nuclease resistant nucleic acids in general and ribonuclease resistant RNAs in particular. Methods of making and using such nucleic acids are disclosed.

Abstract: We have discovered that growth hormones from ternary complexes with their receptors in which site 1 on the hormone first binds to one molecule of receptor and then hormone site 2 then binds to another molecule of receptor, thereby producing a 1:2 complex. We believe this phenomenon is shared by other ligands having similar conformational structure. Assays based on this phenomenon are useful for identifying ligand agonists and antagonists. Sites 1 and 2 are structurally identified to facilitate generation of amino acid sequence variants of ternary complex-forming ligands. Novel variants of growth hormone, prolactin placental lactogen and other related ligands are provided. As a result of our studies with the ternary complex we have determined that selected antibodies to the receptor for these ligands are capable of acting as ligand agonists or antagonists. Novel growth hormones and novel uses for anti-growth hormone receptor antibodies are described.

Abstract: The invention provides an isolated and purified nucleic acid molecule encoding mammalian immunoglobulin A inducing protein (IGIP), and methods of using the IGIP nucleic acid molecule and IGIP.

Abstract: The present invention relates to polynucleotide and polypeptide molecules for Zcyto21, an interferon-like protein, which is most closely related to interferon-? at the amino acid sequence level. The present invention also includes antibodies to the Zcyto21 polypeptides, and methods of using the polynucleotides and polypeptides.

Abstract: The invention concerns the use of a nucleic acid capable of expressing beta-interferon for the preparation of a pharmaceutical composition for the treatment of an immune disease.

Abstract: The present invention relates to pharmaceutical compositions and methods to improve expression of exogenous polypeptides into vertebrate cells in vivo, utilizing delivery of polynucleotides encoding such polypeptides. More particularly, the present invention provides the use of salts, in particular sodium and potassium salts of phosphate, in aqueous solution, and auxiliary agents, in particular detergents and surfactants, in pharmaceutical compositions and methods useful for direct polynucleotide-based polypeptide delivery into the cells of vertebrates.

Abstract: DNA sequences, recombinant DNA molecules and hosts transformed with them which produce polypeptides displaying a biological or immunological activity of human interferon, the genes coding for these polypeptides and methods of making and using these molecules, hosts, genes and polypeptides. The DNA sequences are characterized in that they code for a polypeptide displaying a biological or immunological activity of human interferon. In appropriate hosts these DNA sequences and recombinant DNA molecules permit the production and identification of genes and polypeptides displaying a biological or immunological activity of human interferon and their use in antiviral and antitumor or anticancer agents.

Abstract: The invention is directed to a lentiviral vector system that can be used for episomal replication of a desired gene. The vector system contains a first vector containing a lentiviral gag gene encoding a lentiviral gag protein, a second vector containing an env gene encoding a functional envelope protein, and a lentiviral pol gene encoding a lentiviral pol protein. The pol protein is at least integrase, but that the integrase has been modified so that it is not capable of integration. This pol gene can be on the first or second vectors or on a third vector. The lentiviral gag and pol and the envelope protein are not on a single vector, and these vectors do not contain nucleotides to effectively package lentiviral RNA. The system also contains another vector having a nucleic acid sequence encoding a target molecule operably linked to a component of an episomal replicon and a lentiviral packaging sequence.

Abstract: Modified proteins, modified interferons &agr;'s and &bgr;'s, phosphorylated modified proteins and DNA sequences encoding the above, applications and uses thereof. Modified phosphorylated Hu-IFN-&agr;-like proteins are provided which carry an identifiable label such as a radio-label. Corresponding phosphorylatable Hu-IFN-&agr;-like proteins which contain a putative phosphorylation site. DNA sequences which encode a Hu-IFN-&agr;-like protein and contain a sequence encoding a putative phosphorylatable site. Appropriate expression vectors are used to transform compatible host cells of various microorganisms, such as E. coli. Numerous uses for the phosphorylated proteins are disclosed.

Abstract: A chicken interferon gene coding for the amino acid sequence of SEQ ID NO:1 is disclosed. There is also disclosed a method of producing chicken interferon recombinantly, a method of isolating other non-mammalian interferon genes, a method of making a transgenic fowl having the chicken interferon gene incorporated therein, and method for delivery of the chicken interferon in the bird, such as by genetic immunization or aerosol. Expression of the gene coding for the amino acid sequence of SEQ ID NO:1 yields functional chicken interferon.

Abstract: A novel human IFN-&agr; subtype and its derivative having an unprecedentedly high specific activity, DNA encoding these proteins, an expression vector having said DNA, a transformant transformed with said expression vector, a method of producing the above human IFN-&agr; and its derivative, and medical uses of the above human IFN-&agr; and its derivative.

Abstract: Hybrid human interferon-&agr; polypeptides, and the corresponding nucleic acid molecules, are disclosed. Pharmaceutical compositions comprising these peptides, and the use of these polypeptides to treat viral disease and regulate cell growth are also provided.

Abstract: The invention is directed to purified and isolated novel ACPL polypeptides, the nucleic acids encoding such polypeptides, processes for production of recombinant forms of such polypeptides, antibodies generated against these polypeptides, fragmented peptides derived from these polypeptides, and the uses of the above.

Abstract: Disclosed herein are methods and means of microbially producing, via recombinant DNA technology, mature human leukocyte interferons, useful in the treatment of viral and neoplastic diseases.

Abstract: Recombinant vectors are provided that render the proliferative response of activated lymphocytes, particularly cytotoxic T lymphocytes, of lessened dependency on T helper cells. The vectors are comprised of a region encoding a stimulatory factor polypeptide operably linked to a heterologous transcriptional control region. Expression of the stimulatory factor polypeptide from the recombinant polynucleotide in an activated lymphocyte renders the proliferative response of less dependent on lymphocyte T helper cells. When the lymphocyte is activated by binding of its cognate antigen the transcriptional control region causes transcription of the stimulatory factor encoding region. The cells containing the vector, particularly CTLs, are of use in immunotherapy.

Abstract: Fusion proteins having a tumor necrosis factor receptor (TNF-R) polypeptide and at least one additional polypeptide covalently fused thereto and selected from an interleukin-1 receptor (IL-1R) and a second TNF-R polypeptide. The receptor polypeptides are preferably fused together by a peptidyl linker. Suitable fusions include, for example, TNF-R-linker-TNF-R; TNF-R-linker-IL-1R; and TNF-R-linker-TNF-R-linker-L-1R molecules.

Abstract: A purified preparation of a peptide consisting essentially of an amino acid sequence identical to that of a segment of a naturally-occurring human protein, said segment being of 10 to 30 residues in length, inclusive, wherein said peptide binds to a human major histocompatibility complex (MHC) class II allotype.

Abstract: Interferons represent an important class of biopharmaceutical products, which have a proven track record in the treatment of a variety of medical conditions, including the treatment of certain autoimmune diseases, the treatment of particular cancers, and the enhancement of the immune response against infectious agents. To date, four types of interferons have been found in humans: interferon-&agr;, interferon-&bgr;, interferon-&ggr;, and interferon-&ohgr;. The present invention provides new forms of human and murine interferon, “interferon-&egr;,” which have applications in diagnosis and therapy.

Abstract: The present invention relates to novel, stable recombinant gamma interferons exhibiting in greater or less degree the antiviral and antiproliferative activity in humans and pH 2 labile properties characteristic of native human gamma interferon. The amino acid sequence of such an interferon comprises, from the N-terminus: X-Y-Asp . . . Thr   1   2       126 wherein X is a methionine residue or hydrogen and Y is a glutamine residue, or, where X is hydrogen, Y is either a glutamine or a pyroglutamate residue.

Abstract: Disclosed herein are methods and means of microbially producing, via recombinant DNA technology, mature human leukocyte interferons, useful in the treatment of viral and neoplastic diseases.

Abstract: Processes for conjugating proteins with polyethylene glycol are disclosed. The disclosed processes provide modified proteins having little or no decrease in their activity and include the steps of deleting at least one amino acid residue on the protein, replacing the at least one amino acid residue with an amino acid residue that does not react with polyethylene glycol, and contacting the protein with polyethylene glycol under conditions sufficient to conjugate the polyethylene glycol to the protein. This advantageous retention of a desired protein activity is attributed to the availability of one or more protein binding sites which is unaltered in the conjugation process and thus remains free to interact with a binding partner ligand or cognate subsequent to the conjugation process.

Abstract: Processes for conjugating proteins with polyethylene glycol are disclosed. The disclosed processes provide modified proteins having little or no decrease in their activity and include the steps of deleting at least one amino acid residue on the protein, replacing the at least one amino acid residue with an amino acid residue that does not react with, polyethylene glycol, and contacting the protein with polyethylene glycol under conditions sufficient to conjugate the polyethylene glycol to the protein. This advantageous retention of a desired protein activity is attributed to the availability of one or more protein binding sites which is unaltered in the conjugation process and thus remains free to interact with a binding partner ligand or cognate subsequent to the conjugation process.

Abstract: Distinct &agr;-, &bgr;- and &ggr;-interferon genes from various animal species have been identified, cloned and expressed to produce the corresponding non-human animal interferon proteins. Specifically disclosed are interferons of bovine, porcine, feline and rabbit origin.

Abstract: Disclosed is the surprising discovery that a single amino acid provides the demarcation between the immunosuppressive and immunostimulatory properties of the cytokine, IL-10. The present invention thus provides mammalian and human IL-10 genes and polypeptides that have immunosuppressive properties, without immunostimulatory side-effects. Also provided are various methods of using the new IL-10 constructs, both in vitro and in vivo, particularly in sole or combination therapies involving immunosuppression, such as in the treatment of inflammatory diseases and disorders, and in transplantation.

Abstract: The present invention provides a novel avian herpesvirus (NAHV) vector and recombinant vaccines made therefrom that are useful to immunize avian species against Marek's disease, infectious laryngotracheitis and Newcastle disease. Methods of immunizing an avian species against Marek's disease, infectious laryngotracheitis and Newcastle disease are also provided.

Abstract: Chimeric proteins and DNA encoding chimeric proteins are provided, where the chimeric proteins are characterized by an extracellular domain capable of binding to a ligand in a non-MHC restricted manner, a transmembrane domain and a cytoplasmic domain capable of activating a signaling pathway. The extracellular domain and cytoplasmic domain are not naturally found together. Binding of ligand to the extracellular domain results in transduction of a signal and activation of a signaling pathway in the cell, whereby the cell may be induced to carry out various functions relating to the signalling pathway. A wide variety of extracellular domains may be employed as receptors, where such domains may be naturally occurring or synthetic. The chimeric DNA may be used to modify lymphocytes as well as hematopoietic stem cells as precursors to a number of important cell types.

Abstract: DNA fragments which contain a sequence of DNA which encodes a protective peptide-fused &agr;-hANP in which the protective peptide has a C-terminus lysine residue which is directly fused to the N-terminus of the &agr;-hANP, vectors which contain such a DNA sequence, and microorganisms transformed which such a vector are useful for the production of &agr;-hANP.

Abstract: The present invention relates to plasmids suitable for IL-2 expression, particularly, human IL-2 expression, and related methods.

Abstract: 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 &agr;/&bgr; 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.

Abstract: The invention includes interferon-tau (IFN&tgr;) pharmaceutical compositions useful for oral administration to treat autoimmune disorders (particularly multiple sclerosis), cell proliferative disorders and viral disease.

Abstract: The present invention provides novel nucleic acids encoding IL-1 Hy2, a novel member of the Interleukin-1 Receptor Antagonist family, the novel polypeptides encoded by these nucleic acids and uses of these and related products.

Abstract: Provided are compositions and methods of use for insect cells comprising baculovirus encoding non-surface expressed proteins and peptides. The claimed invention particularly relates to compositions comprising insect cells containing baculovirus that express cytokines. Such compositions may be administered by, for example, direct intratumoral injection into tumors in mammals, resulting in tumor reduction or recission. Another aspect of the claimed invention concerns methods of promoting resistance to the reoccurence of tumors in mammals who have undergone such tumor recission. In a specific aspect of the claimed invention, the mammals are human subjects presenting with various forms of cancer.

Abstract: Methods and model systems for identifying and characterizing new therapeutic agents, particularly proteins, which mimic or inhibit the activity of all interferons, Type I interferons, IFN-&agr;, IFN-&bgr;, or IFN-&ggr;. The method comprises administering an interferon selected from the group consisting of IFN-&agr;, IFN &bgr;, IFN-&tgr;, IFN-&ohgr;, IFN-&ggr;, and combinations thereof to cultured cells, administering the candidate agent to a duplicate culture of cells; and measuring the effect of the candidate agent and the interferon on the transcription or translation of one or, preferably, a plurality of the interferon stimulated genes or the interferon repressed genes (hereinafter referred to as “ISG's” and “IRGs”, respectively). The model system is an array with gene probes that hybridize with from about 100 to about 5000 ISG and IRG transcripts.

Abstract: Interferons represent an important class of biopharmaceutical products, which have a proven track record in the treatment of a variety of medical conditions, including the treatment of certain autoimmune diseases, the treatment of particular cancers, and the enhancement of the immune response against infectious agents. To date, four types of interferons have been found in humans: interferon-&agr;, interferon-&bgr;, interferon-&ggr;, and interferon-&ohgr;. The present invention provides new forms of human and murine interferon, “interferon-&egr;,” which have applications in diagnosis and therapy.

Abstract: The present invention is drawn to the use of attenuated Coxsackievirus cardiotropic virus vectors as efficient gene transfer vectors to deliver immunomodulatory or other biologically active proteins and/or antigenic epitopes in transient infections to aid in preventing, ameliorating, and/or ablating infectious viral heart disease and reducing, or ablating entirely, heart transplant rejection. Additionally, other organs or tissues may be targeted with specific picornaviruses. In particular, an attenuated CVB3 viral vector able to express a cytokine is provided. This cytokine-expressing viral vector is able to deliver the cytokine to a target tissue and reduce disease symptoms.

Abstract: The invention provides a new human interferon (IFN)-&bgr; variant cloned from an amniotic cell library, a cDNA encoding it, and processes for its production and purification. The variant, termed interferon beta-cis, differs from previously known hIFN-&bgr; isoforms by the substitution of a Cys residue for the Tyr present at position 60. Recombinant IFN beta-cis exhibits antiviral activity characteristic of IFN-&bgr;.

Abstract: Interferons represent an important class of biopharmaceutical products, which have a proven track record in the treatment of a variety of medical conditions, including the treatment of certain autoimmune diseases, the treatment of particular cancers, and the enhancement of the immune response against infectious agents. The present invention provides a new form of murine interferon-&agr;, which has applications in diagnosis and therapy.

Abstract: The present invention provides a complex comprising a biologically active substance and a ligand that recognizes CD16.

Abstract: The invention concerns a human interferon, designated PRO655, and its variants and derivatives. The interferon is related to but distinct from members of the IFN-&agr; family and from IFNs-&bgr; and -&ggr;. Nucleic acid encoding the polypeptide, and methods and means for their recombinant production are also included.

Abstract: The invention concerns a human interferon-&egr;, originally designated PRO655, and its variants and derivatives. The interferon is related to but distinct from members of the IFN-&agr; family and from IFNs-&bgr; and -&ggr;. Nucleic acid encoding the polpypeptide, and methods and means for their recombinant production are also included.

Abstract: A desired protein having the formula:

Abstract: The invention provides artificial chromosome constructs containing foreign nucleic acid sequences, such as viral nucleic acid sequences, and methods of using these artificial chromosome constructs for therapy and recombinant virus production.