Abstract: The present invention relates to chimeric transmembrane immunoreceptors, named “zetakines,” comprised of an extracellular domain comprising a soluble receptor ligand linked to a support region capable of tethering the extracellular domain to a cell surface, a transmembrane region and an intracellular signalling domain. Zetakines, when expressed on the surface of T lymphocytes, direct T cell activity to those specific cells expressing a receptor for which the soluble receptor ligand is specific. Zetakine chimeric immunoreceptors represent a novel extension of antibody-based immunoreceptors for redirecting the antigen specificity of T cells, with application to treatment of a variety of cancers, particularly via the autocrin/paracrine cytokine systems utilized by human maligancy.

Abstract: 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.

Abstract: Compositions are provided that are targeted to tumors or tumor-associated neovasculature and enhance the function of tumor-infiltrating T cells. The compositions include fusion proteins that contain a T cell binding domain and a tumor/tumor-associated neovasculature targeting domain. The fusion proteins optionally contain a peptide/polypeptide linker domain and a domain that mediates dimerization or multimerization. The T cell binding domain can be a costimulatory molecule. Methods for using the fusion proteins to enhance an immune response are provided. Therapeutic uses for the disclosed compositions include the induction of tumor immunity.

Abstract: The invention relates to novel polyalkylene glycol compounds and methods of using them. In particular, compounds comprising a novel polyethylene glycol conjugate are used alone, or in combination with antiviral agents to treat a viral infection, such as chronic hepatitis C.

Abstract: Conjugates of hydroxyalkyl starch and a protein are provided herein. The conjugates are formed by a convalent linkage between the hydroxyalkyl starch or a derivative of the hydroxyalkyl starch and the protein. Methods of producing the conjugates and the use of the conjugates also are provided herein.

Abstract: The present invention relates to the field of recombinant protein production in bacterial hosts. It further relates to extraction of soluble, active recombinant protein from an insoluble fraction without the use of denaturation and without the need for a refolding step. In particular, the present invention relates to a production process for obtaining high levels a soluble recombinant Type 1 interferon protein from a bacterial host.

Abstract: Inactivated protein derivatives of the hIFN-? that preserve affinity to the hIFN-? receptor are useful in the treatment of autoimmune diseases, especially multiple sclerosis.

Abstract: Treatment of stroke with an antibody specific to IL-20, e.g., monoclonal antibody 7E.

Abstract: The present invention encompasses albumin fusion proteins. Nucleic acid molecules encoding the albumin fusion proteins of the invention are also encompassed by the invention, as are vectors containing these nucleic acids, host cells transformed with these nucleic acids vectors, and methods of making the albumin fusion proteins of the invention and using these nucleic acids, vectors, and/or host cells. Additionally the present invention encompasses pharmaceutical compositions comprising albumin fusion proteins and methods of treating, preventing, or ameliorating diseases, disorders or conditions using albumin fusion proteins of the invention.

Abstract: An IL-17 binding molecule, in particular an antibody to human IL-17, more preferably a human antibody to human IL-17 is provided, wherein the hypervariable regions of the heavy and light chains have amino acid sequences as defined, for use in the treatment of a solid or hematological malignant diseases.

Abstract: Novel polypeptides and polynucleotides encoding same are provided. Also provided methods and pharmaceutical compositions which can be used to treat various disorders such as cancer, immunological-related, blood-related and skin-related disorders using the polypeptides and polynucleotides of the present invention. Also provided are methods and kits for diagnosing, determining predisposition and/or prognosis of various disorders using as diagnostic markers the novel polypeptides and polynucleotides of the present invention.

Abstract: Vaccine composition containing IL-15 for active immunization to treatment diseases related to over-expression of this cytokine. The technical aim pursued in this invention is to inhibit IL-15 activity through development of a therapeutic vaccine which elicits IL-15 neutralizing antibodies in the immunized host. IL-15 can be presented in this vaccine composition either alone or coupled to a carrier such as the P64k protein with a vaccine adjuvant such as Aluminum hydroxide. Besides, this invention is related to the use of this vaccine for treatment of Rheumatoid arthritis and other IL-15 over-expressing related diseases, and leukemia, where this cytokine acts as a growth factor.

Abstract: Chemokines may be administered to a patient for immunotolerization. Chemokines include CCL19 and CCL21. Materials and methods for accomplishing tolerization and described.

Abstract: A method for treating IL-20 induced inflammation. An antagonist to IL-20 is administered to treat inflammation and associated diseases. The antagonist can be an antibody that binds to IL-20 or its receptor or a soluble receptor that binds to IL-20. Examples of such diseases are adult respiratory disease, psoriasis, eczema, contact dermatitis, atopic dermatitis, septic shock, multiple organ failure, inflammatory lung injury, bacterial pneumonia, inflammatory bowel disease, rheumatoid arthritis, asthma, ulcerative colitis and Crohn's disease.

Abstract: An antibody binding to IL-17 characterized by binding to the same IL-17 epitope to which monoclonal antibody 3C1 binds, and being of human IgG1 isotype modified in the hinge region at amino acid position 216-240, preferably at amino acid position 220-240, between CH1 and CH2 and/or in the second inter-domain region at amino acid position 327-331 between CH2 and CH3 has advantageous properties for the treatment of inflammatory diseases.

Abstract: The present invention relates to a G-protein coupled receptor and a novel ligand therefor. The invention provides screening assays for the identification of candidate compounds which modulate the activity of the G-protein coupled receptor, as well as assays useful for the diagnosis and treatment of a disease or disorder related to the dysregulation of G-protein coupled receptor signaling.

Abstract: Conjugates of hydroxyalkyl starch and a protein are provided herein. The conjugates are formed by a convalent linkage between the hydroxyalkyl starch or a derivative of the hydroxyalkyl starch and the protein. Methods of producing the conjugates and the use of the conjugates also are provided herein.

Abstract: The present invention relates to novel cytokines, which have a modified selectivity/specificity for their cognate receptors. In particular, the invention relates to a variant TRAIL protein, which has superior selectivity for the death receptor 4 (TRAIL-RI) over the death receptor 5 (TRAIL-R2). In addition, the invention relates to a variant TRAIL protein which exhibits superior selectivity for the death receptor 4 (TRAIL-R1) over the decoy receptors DcR1 (TRAIL-R3) and DcR2 (TRAIL-R4).

Abstract: Disclosed is a protein complex, comprising a physiologically active polypeptide, a dimeric protein and a non-peptidyl polymer having three functional ends (3-arm), with the linkage of both the physiologically active polypeptide and the dimeric protein to the 3-arm non-peptidyl polymer via respective covalent bonds. The protein complex guarantees the long acting activity and biostability of a physiologically active polypeptide. Having the ability to maintain the bioactivity of physiologically active polypeptides or peptides highly and to significantly improve the serum half life of the polypeptides or peptides, the protein complex can be applied to the development of sustained release formulations of various physiologically active polypeptide drugs. Also, it utilizes raw materials including the physiologically active polypeptides without significant loss, thereby increasing the production yield. Further, it can be easily purified.

Abstract: Compositions of modified cytokines and uses thereof generated using processes and systems for the high throughput directed evolution of peptides and proteins, particularly cytokines that act in complex biological settings, are provided. Also provided are modified cytokines formulated for oral delivery and uses thereof to treat diseases and conditions mediated by cytokines.

Abstract: The present invention relates, in general, to RNA silencing and, in particular, to a method of effecting targeted delivery of an RNA silencing moiety using a targeting moiety that binds to a cell surface receptor and mediates internalization of the RNA silencing moiety to be accessible to Dicer. Also provided is a chimeric nucleic acid molecule comprised of a targeting moiety and an RNA silencing moiety, wherein the targeting moiety is an aptamer and the RNA silencing moiety comprises a Dicer substrate.

Abstract: Compositions comprising TNF receptor super-family member 25 (TNFR25) agents, attenuate Treg activity and, by comparison with other TNFR members, only weakly costimulates T effector cell (Teff) activity. Alternatively spliced TNFR25 modulates the functional effects of TNFR25 signaling These agents have a wide therapeutic applicability in the treatment of diseases by modulating immune responses. In addition these agents can be used in conjunction with vaccines to enhance the immune response.

Abstract: Cosmetic and therapeutic compositions for skin care, containing a transgenic plant extract containing a growth factor, or a growth factor purified from transgenic plants, or a mixture of growth factors derived from transgenic plants as extracts or in purified form, for use in topical therapeutic and/or cosmetic applications. Importantly, this invention makes safer growth factors available for use for cosmetic and topical treatment. These growth factors do not carry the risk of unwanted contaminants and transmissible agents that can result from animals or animal cell based expression systems, and the recombinant growth factors that plant expression systems provide are post-translationally modified proteins.

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: The present invention has an object to provide a tumor necrosis factor mutant protein, particularly, a tumor necrosis factor mutant protein specific to TNF-R1 or TNF-R2; tumor necrosis factor inhibitor; or tumor necrosis factor preparation containing it as an effective ingredient, and the object is solved by providing a tumor necrosis factor mutant protein where one or more amino acid residues selected from the group consisting of 29th, 31st, 32nd, 145th, 146th and 147th, or the group consisting of 84th to 89th from the N-terminal of the amino acid sequence of SEQ ID NO:1 is/are replaced with other amino acid residue(s); a tumor necrosis factor inhibitor; and a tumor necrosis factor preparation containing it as an effective ingredient.

Abstract: The present invention relates to novel methods for the design of proteins, in particular, cytokines. These methods allow the stabilisation of such cytokines, as well as modification of their selectivity/specificity for their cognate receptors. The invention also relates to various modified proteins that have been designed by the methods of the invention.

Abstract: The present disclosure generally teaches compositions comprising SDF-1 mimetics and methods of using them to modulate an activity of a cell having an SDF-1 receptor by binding the SDF-1 receptor to an SDF-1 mimetic. The cell can be a hematopoietic cell, for example, and can be selected from a group consisting of hematopoietic stem cells, hematopoietic progenitor cells, primitive granulocytes, primitive erythroid cells, leukocytes, and neutrophils. In some embodiments, the activity can include the rate of multiplication of the cell or, where the cell is a quiescent cell, the binding can repress the activation of the quiescent cell. Other embodiments of the present invention are taught herein.

Abstract: The present invention relates to compositions and methods relating to an interleukin18-inducible cytokine termed tumor necrosis factor-alpha inducing factor (TAIF) or interleukin-32 (IL-32). In particular, the present invention provides compositions and methods for treating autoimmune diseases and cancer, in part by regulation of tumor necrosis factor-alpha expression.

Abstract: A complex comprising at least one target protein and at least one binding molecule having a binding affinity for said target protein, wherein said molecule having a binding affinity is covalently or non-covalently bound to at least one water-soluble polymer

Abstract: Nucleic acids encoding a new family of chemokines, the CX3C family, from a mammal, reagents related thereto, including specific antibodies, and purified proteins are described. Methods of using said reagents and related diagnostic kits are also provided.

Abstract: Provided are methods and compositions for selectively targeting CRKL through the use of targeting peptides. Selective targeting of secreted CRKL through the use of a targeting peptide may be used, for example, in the treatment of cancer to deliver a chemotherapeutic compound, fusion protein, or fusion construct to a cancer cell or tissue.

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: Novel biologically active compounds of the general formula (I) in which one of X and X? represents a polymer, and the other represents a hydrogen atom; each Q independently represents a linking group; W represents an electron-withdrawing moiety or a moiety preparable by reduction of an electron-withdrawing moiety; or, if X? represents a polymer, X-Q-W— together may represent an electron withdrawing group; and in addition, if X represents a polymer, X? and electron withdrawing group W together with the interjacent atoms may form a ring; each of Z1 and Z2 independently represents a group derived from a biological molecule, each of which is linked to A and B via a nucleophilic moiety; or Z1 and Z2 together represent a single group derived from a biological molecule which is linked to A and B via two nucleophilic moieties; A is a C1-5 alkylene or alkenylene chain; and B is a bond or a C1-4 alkylene or alkenylene chain; are formed by conjugating a suitable polymer to a suitable biologically active molecule via nuc

Abstract: We disclose granulocyte colony stimulating factor fusion polypeptides; nucleic acid molecules encoding said polypeptides and methods of treatment that use said proteins.

Abstract: The present invention relates to complete oxidized LDL specific IgG fused or conjugated with at least one of the proteins of the group IL-10, TIMPs, and TGF?s to be used in a medicine, the use thereof for treatment of atherosclerosis and prevention of clinical events in patients with atherosclerosis, pharmaceutical compositions containing the same, as well as method for treatment of atherosclerosis and prevention of clinical events in patients with atherosclerosis.

Abstract: DNA plasmids containing sequences coding for different fragments of 185neu oncoprotein which are able to induce an immune response against p185neu-overexpressing tumors, and pharmaceutical compositions thereof are described.

Abstract: The invention provides an aptamer possessing an inhibitory activity against IL-17, as well as a complex comprising an aptamer possessing a binding activity or inhibitory activity against IL-17 and a functional substance (for example, affinity substances, substances for labeling, enzymes, drug delivery vehicles, drugs and the like). The invention also provides a pharmaceutical drug, cell migration inhibitor, diagnostic reagent, detection probe, carrier, labeling agent, and the like comprising the aforementioned aptamer or complex, and methods of detecting and purifying IL-17 by using the aforementioned aptamer or complex.

Abstract: The present invention provides for an isolated polynucleotide sequence encoding a chimeric CD154, comprising a first nucleotide sequence encoding an extracellular subdomain of non-human CD154, preferably murine CD154, that replaces a cleavage site of human CD154, and a second nucleotide sequence encoding an extracellular subdomain of human CD154 that binds to a human CD154 receptor. The present invention also provides for the chimeric CD154 that is encoded by the above-described polynucleotide sequence, an expression vector and a genetic vector comprising the polynucleotide sequence, a host cell comprising the expression vector or the genetic vector, a process for producing the chimeric CD154, and methods for utilizing the expression vectors and genetic constructs containing the chimeric CD154 polynucleotide sequences.

Abstract: The present invention provides covalent conjugates between a polypeptide and a modifying group, such as a water-soluble polymer (e.g., PEG). The amino acid sequence of the polypeptide includes one or more O-linked glycosylation sequence, each being a substrate for a GIcNAc transferase. The modifying group is covalently linked to the polypeptide via a glycosyl-linking group interposed between and covalently linked to both the polypeptide and the modifying group. In one embodiment, a glucosamine linking group is directly attached to an amino acid residue of the O-linked glycosylation sequence. The invention further provides methods of making polypeptide conjugates. The present invention also provides non-naturally occurring polypeptides that include at least one O-linked linked glycosylation sequence of the invention, wherein each glycosylation sequence is a substrate for a GIcNAc transferase. The invention further provides pharmaceutical compositions that include a polypeptide conjugate of the invention.

Abstract: The present invention provides improved methods for animal-free protein production of high-value heterologous proteins produced in plants, plant derived tissue or plant cells. The invention reduces costs and increases the speed of manufacturing of active ingredients in transgenic plants. Furthermore, the invention improves the quality and safety of heterologous proteins produced in plants. The enhanced control of conditions in manufacturing of heterologous industrial and biopharmaceutical heterologous proteins obtained by the present invention with the combination of soil-less, hydroponic culture on conveyor belts with distinct nutrient zones in soilless greenhouses improves greatly the consistency of protein production in transgenic plants and conformity with quality control procedures applied for the manufacturing of active ingredients by the pharmaceutical industry, cosmetic industry, fine chemicals industry and veterinary industry.

Abstract: Isolated polynucleotides encoding Cynomolgus monkey Toll-Like Receptor 3 (cynoTLR3), polypeptides obtainable from expression of these polynucleotides, recombinant cells, methods and uses of these are disclosed.

Abstract: The present invention concerns methods and compositions for forming PEGylated complexes of defined stoichiometry and structure. In preferred embodiments, the PEGylated complex is formed using dock-and-lock technology, by attaching a target agent to a DDD sequence and attaching a PEG moiety to an AD sequence and allowing the DDD sequence to bind to the AD sequence in a 2:1 stoichiometry, to form PEGylated complexes with two target agents and one PEG moiety. In alternative embodiments, the target agent may be attached to the AD sequence and the PEG to the DDD sequence to form PEGylated complexes with two PEG moieties and one target agent. In more preferred embodiments, the target agent may comprise any peptide or protein of physiologic or therapeutic activity. The PEGylated complexes exhibit a significantly slower rate of clearance when injected into a subject and are of use for treatment of a wide variety of diseases.

Abstract: The present invention provides ILT-2 variants having the property of binding to a given Class IpMHC with a KD of less than or equal to 1 ?M and/or an off-rate (Koff) of 2 S?1 or slower AND said polypeptide has at least a 45% identity and/or 55% similarity to SEQ ID NO: 19 AND said polypeptide inhibits CD8 binding to the given pMHC to a greater extent than the polypeptide SEQ ID NO: 3, CHARACTERISED IN THAT said polypeptide comprises an amino acid sequence selected from one of SEQ ID NOs 6 to 69. Such polypeptides are useful, either alone or associated with a therapeutic agent, for the inhibition of cyto-toxic T cell (CTL) responses.

Abstract: We describe modified peptide linkers that function to link at least first and second polypeptides wherein said modified peptide linker comprises a motif for the addition of a sugar moiety.

Abstract: A novel IFN-?/? independent ligand receptor system which upon engagement leads, among other things, to the establishment of an anti-viral state is disclosed. Further disclosed are three closely positioned genes on human chromosome 19 that encode distinct but highly homologous proteins, designated IFN-?1, IFN-?2, IFN-?3, based, inter alia, in their ability to induce antiviral protection. Expression of these proteins is induced upon viral infection. A receptor complex utilized by all three IFN-? proteins for signaling is also disclosed. The receptor complex is generally composed of two subunits, a novel receptor designated IFN-?R1 or CRF2-12, and a second subunit, IL-10R2 or CRF2-4, which is also a shared receptor component for the IL-10 and IL-22 receptor complexes. The gene encoding IFN-?R1 is generally widely expressed, including many different cell types and tissues. Expression of these proteins is induced by immune events, including, for example, upon viral infection.

Abstract: The present invention provides unstructured recombinant polymers (URPs) and proteins containing one or more of the URPs. The present invention also provides microproteins, toxins and other related proteinaceous entities, as well as genetic packages displaying these entities. The present invention also provides recombinant polypeptides including vectors encoding the subject proteinaceous entities, as well as host cells comprising the vectors. The subject compositions have a variety of utilities including a range of pharmaceutical applications.

Abstract: A method of treating an inflammation in a subject thereof is provided. The method comprising administering to the subject a therapeutically effective amount of CCL2, thereby treating the inflammation. Also provided are pharmaceutical compositions and unit dosage forms which comprise CCL2 for the treatment of inflammation.

Abstract: The invention provides processes for preparing a cell-binding agent chemically coupled to a drug. A first process comprises covalently attaching a linker to a cell-binding agent, an optional purification step, conjugating a drug to the cell-binding agent, a subsequent purification step, and optional holding steps. A second process comprises covalently attaching a linker to a cell-binding agent, a purification step, conjugating a drug to the cell-binding agent, a subsequent purification step, holding steps, and optionally a tangential flow filtration (TFF) step.

Abstract: The invention relates to an inhibitor of endogenous human interferon-gamma (hIFN-ϝ) in autoimmune diseases, especially in multiple sclerosis. More precisely, the invention relates to inactivated protein derivatives of the hIFN-ϝ with preserved affinity to the hIFN-ϝ receptor. The derivatives represent genetically modified variants of hIFN-ϝ where the C-terminal part of the molecule is either deleted or replaced with a polypeptide sequence of another human protein and a recombinant hIFN-ϝ inactivated by physical or chemical methods.

Abstract: Disclosed herein are methods and compositions dock and lock (DNL) complexes comprising an AD moiety selected from an AKAP protein and a DDD moiety selected from a protein kinase A regulatory subunit. Also disclosed are fusion proteins comprising an AD moiety or DDD moiety attached to an effector moiety. The DDD moieties form dimers that bind to the AD moiety to form the DNL complexes. The effector moieties may be selected from a wide range of known effector moieties that produce one or more physiological effects, including but not limited to cell death. The DNL complexes may further comprise one or more diagnostic and/or therapeutic agents. The DNL complexes are of use for treating and/or diagnosing a variety of diseases or conditions.