Abstract: This invention provides a crystalline recombinant interferon (rSIFN-co) having (i) the same amino acid sequence as that of human consensus interferon, and (ii) altered three-dimensional structure as compared to IFN-?2b. The interferon of the present invention exhibits enhanced biological activities. The present invention also provides a structure model of said interferon useful for drug screening and/or drug design and the mimetic of said interferon. The invention further provides methods of designing and using new recombinant interferons with altered spatial configuration and three-dimensional structure.

Abstract: A liquid aqueous pharmaceutical formulation is described which has a high protein concentration, a pH of between about 4 and about 8, and enhanced stability.

Abstract: The instant invention provides soluble fusion protein complexes and IL-15 variants that have therapeutic and diagnostic use, and methods for making such proteins. The instant invention additionally provides methods of stimulating or suppressing immune responses in a mammal using the fusion protein complexes and IL-15 variants of the invention.

Abstract: The present invention relates to a system and method for producing high levels of autologous IL-1RA cytokine, comprising: a blood collection vessel (1), a cover (4), a portion of separation gel (2), an anticoagulant portion (3), a plasma collection syringe comprising a sharp needle (9), a buffy coat collection syringe (11) and an incubation tube with cover (15). The vessel is adapted such that, when containing the whole blood (5), and centrifuged after treatment, yields separation fractions comprising, a first fraction of RBCs sediment (6), a second fraction of said gel (2), a third fraction comprising WBCs, platelets and), and fourth fraction of plasma solution (8).

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.

Abstract: Provided are engineered soluble hIL-17RA receptors with high affinity to hIL-17 that inhibit downstream IL17A induced signaling events in cells. Also provided are methods of inhibiting hIL-17A induced secretion of CXCL1 and/or IL-6 in cells, as well as methods of treating inflammation and/or inflammatory disorders in a subject.

Abstract: The invention relates to materials and methods of conjugating a water soluble polymer to an oxidized carbohydrate moiety of a therapeutic protein comprising contacting the oxidized carbohydrate moiety with an activated water soluble polymer under conditions that allow conjugation. More specifically, the present invention relates to the aforementioned materials and methods wherein the water soluble polymer contains an active aminooxy group and wherein an oxime or hydrazone linkage is formed between the oxidized carbohydrate moiety and the active aminooxy group on the water soluble polymer, and wherein the conjugation is carried out in the presence of a nucleophilic catalyst.

Abstract: The present invention concerns methods and compositions comprising an anti-IGF-1R antibody or fragment thereof for treatment of cancer or autoimmune disease. Preferably, the cancer is renal cell carcinoma, breast cancer or pancreatic cancer. The anti-IGF-1R antibody or fragment may be part of a complex, such as a DOCK-AND-LOCK™ (DNL™) complex. Preferably, the DNL™ complex also comprises a second antibody, a second antibody fragment, an affibody or a cytokine. More preferably, the cytokine is interferon-?2b. Most preferably, the second antibody, second fragment or affibody binds to IGF-1R, TROP2 or CEACAM6. The anti-IGF-1R antibody or complex may be administered alone or in combination with a therapeutic agent, such as an mTOR inhibitor.

Abstract: Disclosed is a method for refolding a protein or peptide that does not contain essential disulfides and that contains at least one free cysteine residue. Also disclosed are polymer IFN-? conjugates that have been created by the chemical coupling of polymers such as polyethylene glycol moieties to IFN-?, particularly via a free cysteine in the protein. Also disclosed are analogs of bioactive peptides that may be used to create longer acting versions of the peptides, including analogs of glucagon, glucagon-like peptide-1 (GLP-1), GLP-2, Gastric inhibitory peptide (GIP), PYY, exendin, ghrelin, gastrin, amylin, and oxyntomodulin.

Abstract: The invention relates to a combination medicament for treatment of malignant neoplastic disease. The combination medicament comprises an IL-12 polypeptide having a biological activity of IL-12 or a nucleic acid expression vector comprising a sequence encoding such IL-12 polypeptide, and a non-agonist CTLA-4 ligand or non-agonist PD-1 ligand, particularly an anti-CTLA-4 or anti-PD-1 immunoglobulin G.

Abstract: The present invention is generally directed to internally functionalized graphene substrates, methods of making such substrates and methods of using such substrates. In one aspect, the present invention is a graphene substrate. The substrate comprises edge and non-edge regions. Organic or inorganic molecules are bound to the non-edge regions of the substrate, and the organic or inorganic molecules are present on the substrate edges at a population greater than about one molecule per 10,000 nm2.

Abstract: The present invention comprises compositions and methods for delivery systems of agents, including therapeutic compounds, pharmaceutical agents, drugs, detection agents, nucleic acid sequences and biological factors. In general, the nanotherapeutic compositions of the present invention comprise a platform comprising a colloidal metal, a targeting ligand such a tumor necrosis factor, a stealth agent such as polyethylene glycol, and one or more diagnostic or therapeutic agents for delivery. The invention also comprises methods and compositions for making such nanotherapeutic compositions and for the treatment of cancer.

Abstract: The present invention relates to biologically active polypeptides linked to one or more accessory polypeptides. 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 liquid aqueous pharmaceutical formulation is described which has a high protein concentration, a pH of between about 4 and about 8, and enhanced stability.

Abstract: Quantitation of analytes, including but not limited to peptides, polypeptides, and proteins, in mass spectrometry using a labeled peptide coupled to a reporter, and a universal reporter.

Abstract: Liquid interferon compositions having a pH between 4.0 and 7.2 are described. The compositions comprise interferon-beta and a stabilizing agent at between about 0.3% and 5% by weight which is an amino acid selected from the group consisting of acidic amino acids, arginine and glycine. If needed, salt is added to provide sufficient ionic strength. The liquid composition has not been previously lyophilized or previously cavitated. The liquid is preferably contained within a vessel having at least one surface in contract with the liquid that is coated with a material inert to adsorption of interferon-beta. A kit for parenteral administration of a liquid interferon formulation and a method for stabilizing liquid interferon compositions are also described.

Abstract: An interferon beta polypeptide comprising interferon-beta 1a coupled to a polymer containing a polyalkylene glycol moiety wherein the interferon-beta-1a and the polyalkylene glycol moiety are arranged such that the interferon-beta-1a has an enhanced activity relative to another therapeutic form of interferon beta (interferon-beta-1b) and exhibits no decrease in activity as compared to non-conjugated interferon-beta-1a. The conjugates of the invention are usefully employed in therapeutic as well as non-therapeutic, e.g., diagnostic, applications.

Abstract: The present invention concerns methods and compositions for making and using bioactive assemblies of defined compositions, which may have multiple functionalities and/or binding specificities. In particular embodiments, the bioactive assembly is formed using dock-and-lock (DNL) methodology, which takes advantage of the specific binding interaction between dimerization and docking domains (DDD) and anchoring domains (AD) to form the assembly. In various embodiments, one or more effectors may be attached to a DDD or AD sequence. Complementary AD or DDD sequences may be attached to an adaptor module that forms the core of the bioactive assembly, allowing formation of the assembly through the specific DDD/AD binding interactions. Such assemblies may be attached to a wide variety of effector moieties for treatment, detection and/or diagnosis of a disease, pathogen infection or other medical or veterinary condition.

Abstract: A method of preparing an oxidised polysaccharide-protein conjugate by oxidising a polysaccharide with an oxidising agent to form an oxidised polysaccharide and combining such oxidised polysaccharide with a protein. The oxidised polysaccharide is reacted with a protein to form a composition comprising a conjugate wherein the oxidised polysaccharide and the protein are conjugated via one or more imine bonds and wherein the oxidised polysaccharide comprises essentially no alpha-hydroxy aldehyde units. The conjugate may be used to provide sustained or latent activity of the protein.

Abstract: Homogeneous preparations of human and murine IL-31 have been produced by mutating one or more of the cysteine residues in the polynucleotide sequences encoding the mature proteins. The cysteine mutant proteins can be shown to either bind to their cognate receptor or exhibit biological activity.

Abstract: The present invention is generally directed to functionalized graphene substrates, methods of making such substrates and methods of using such substrates. In one aspect, the present invention provides a graphene substrate. The substrate comprises edge and non-edge regions, and organic or inorganic molecules are bound to the edge regions of the substrate. The organic or inorganic molecules are present on the substrate edges at a population greater than about one molecule per 10,000 nm.

Abstract: The invention relates to oligomers of a dimer, trimer, quatromer or pentamer of recombinant fusion proteins. The oligomers are characterized in that the recombinant fusion proteins have at least one component A and at least one component B, whereby component A contains a protein or a protein segment with a biological function, in particular with a ligand function for antibodies, for soluble or membranous signal molecules, for receptors or an antibody, or an antibody segment, and component B contains a protein or a protein segment which dimerizes or oligomerizes the dimer, trimer, quatromer or pentamer of the recombinant fusion protein, without the action of third-party molecules. The invention also relates to the use of dimers or oligomers of this type for producing a medicament, to the fusion proteins which cluster in dimers or oligomers and to their DNA sequence and expression vectors or host cells comprising this DNA sequence.

Abstract: The present invention provides an antitumor agent having high safety, which is a molecular target drug against malignant tumors. An anti-malignant tumor agent characterized by containing, as an active ingredient, a substance targeting ribosomal proteins shows increased expression in malignant tumor cells. The substance of the present inventions targeting the ribosomal protein showing increased expression in the malignant tumor cell may be a substance involved in one of biological defense mechanisms which are considered to be intrinsically provided in a living body and prevent onset of disease even if cancer cells develop. Specifically, the ribosomal protein showing increased expression is RPL29 and/or RPS4X.

Abstract: The present invention refers to single-chain fusion proteins comprising three soluble TNF superfamily (TNFSF) cytokine domains and nucleic acid molecules encoding these fusion proteins. The fusion proteins are substantially non-aggregating and suitable for therapeutic, diagnostic and/or research applications.

Abstract: Methods for enhancing or stimulating hematopoiesis including the step of administering Interleukin-12 (IL-12) to yield hematopoietic recovery in a mammal in need. Preferred methods include the step of administering IL-12 as an adjuvant therapy to alleviate the hematopoietic toxicities associated with one or more treatment regimens used to combat a disease state. Other methods include administering IL-12 to ameliorate various hematopoietic deficiencies. Still other methods are directed to uses of IL-12 for in-vivo proliferation of hematopoietic repopulating cells, hematopoietic progenitor cells and hematopoietic stem cells. Other disclosed methods are directed to uses of IL-12 for bone marrow preservation or recovery.

Abstract: The present invention provides a method for industrial-scale protein separation by reverse phase chromatography by use of a buffer system and an additional salt.

Abstract: The present invention provides fusion proteins including an autoimmune antigen, an allergen antigen or an alloantigen, and an anti-inflammatory cytokine. Compositions and methods including the fusion proteins are also provided.

Abstract: A fusion protein comprising domain (a) which is a functional fragment of hTRAIL protein sequence, which fragment begins with an amino acid at a position not lower than hTRAIL95, or a homolog of said functional fragment having at least 70% sequence identity, preferably 85% identity and ending with the amino acid hTRAIL281; and at least one domain (b) which is a sequence of a cytolytic effector peptide forming pores in the cell membrane, wherein the sequence of domain (b) is attached at the C-terminus or N-terminus of domain (a). The fusion protein can be used for the treatment of cancer diseases.

Abstract: A liquid aqueous pharmaceutical formulation is described which has a high protein concentration, a pH of between about 4 and about 8, and enhanced stability.

Abstract: A liquid aqueous pharmaceutical formulation is described which has a high protein concentration, a pH of between about 4 and about 8, and enhanced stability.

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 an amine group; or Z1 and Z2 together represent a single group derived from a biological molecule which is linked to A and B via two amine groups; 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 amine groups in sai

Abstract: Aspects and embodiments of the instant disclosure provide therapeutic methods and compositions comprising inter-leukin 12 (IL-12) useful for treating radiation-induced damage in a subject. In particular, the instant disclosure provides methods and compositions for radiation protection and/or radiation toxicity mitigation for the treatment of acute radiation syndrome and radiation induced toxicity associated with the treatment of cutaneous T-cell lymphoma.

Abstract: In certain embodiments, this disclosure relates to conjugates comprising GM-CSF and IL-7 and uses related thereto, e.g., enhancing the adaptive immune system. Typically the GM-CSF and IL-7 are connected by a polymer linker, e.g., polypeptide. In certain embodiments, the disclosure relates to nucleic acids encoding these polypeptide conjugates, vectors comprising nucleic acid encoding polypeptide conjugates, and protein expression systems comprising these vectors such as infectious viral particles and host cells comprising such a nucleic acids.

Abstract: The object of the present invention is to provide a glycosylated polypeptide having uniform sugar chain structure which has interferon ? activity. It was found that a glycosylated polypeptide having uniform sugar chain structure as well as having interferon ? activity can be prepared by a method comprising a step of synthesizing a glycosylated peptide fragment and at least two peptide fragments and a step of linking the glycosylated peptide fragment and the at least two peptide fragments.

Abstract: A liquid aqueous pharmaceutical formulation is described which has a high protein concentration, a pH of between about 4 and about 8, and enhanced stability.

Abstract: Disclosed are antibody fusion proteins with a modified FcRn binding site and nucleic acid molecules encoding them. The antibody fusion protein include two polypeptide chains, wherein the first polypeptide chain includes a biologically active molecule linked to at least a portion of an immunoglobulin constant region. The second polypeptide chain includes at least a portion of an immunoglobulin constant region. One of the polypeptide chains includes a mutation in the FcRn binding site that reduces binding to FcRn. Also disclosed are methods of producing the fusion proteins and methods of using the fusion proteins for treating diseases and conditions alleviated by the administration of the fusion proteins.

Abstract: Modified human four helical bundle (4HB) polypeptides and uses thereof are provided.

Abstract: The present application provides human antibodies and antigen binding fragments thereof that specifically bind to the human interleukin-22 (IL-22) and methods of using those antibodies, for example, in diagnosing, treating or preventing inflammatory disorders, autoimmune diseases, allergies, septic shock, infectious disorders, transplant rejection, cancer, and other immune system disorders.

Abstract: The present invention relates to mutant IL-2 polypeptides that act as receptor antagonists. The mutant IL-2 polypeptides bind CD 25 but do not activate the IL-2 receptor. Also provided are methods of using the mutant IL-2 polypeptides, for example, to treat a patient who has cancer or a viral infection. The mutant polypeptides can also be used in various delivery systems.

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: This invention provides crystalline recombinant interferon (rSIFN-co (SEQ ID NO: 1)) having (i) the same amino acid sequence as that of human consensus interferon, and (ii) altered three-dimensional structure as compared to IFN-?2b. The interferon of the present invention exhibits enhanced biological activities. The present invention also provides a structural model of said interferon useful for drug screening and/or drug design, and mimetics of said interferon.

Abstract: IFN-alpha mutants are obtained by substituting Cys for Tyr at position 85 or 86 in existing IFN-alpha. Their polyethylene glycol derivatives with high in vitro antiviral activity and prolonged in vivo half-life are also provided, wherein a polyethylene glycol moiety is covalently bound to the free Cys residue of an IFN-alpha mutant. The preparation methods of PEG derivatives of IFN-alpha mutants and medical compositions comprising the derivatives are also provided. The test results showed that the IFN-alpha mutants of the present invention are ready to prepare and have high activity; their polyethylene glycol derivatives have extended lifetime in the body and low clearance rate.

Abstract: This disclosure relates to a modified ?-helical bundle cytokine, with reduced activity via an ?-helical bundle cytokine receptor, wherein the ?-helical bundle cytokine is specifically delivered to target cells. Preferably, the ?-helical bundle cytokine is a mutant, more preferably it is a mutant interferon, with low affinity to the interferon receptor, wherein the mutant interferon is specifically delivered to target cells. The targeting is realized by fusion of the modified ?-helical bundle cytokine to a targeting moiety, preferably an antibody. This disclosure relates further to the use of such targeted modified ?-helical bundle cytokine to treat diseases. A preferred embodiment is the use of a targeted mutant interferon, to treat diseases, preferably viral diseases and tumors.

Abstract: In certain embodiments, this disclosure relates to conjugates comprising GM-CSF and IL-9 and uses related thereto, e.g., enhancing the adaptive immune system. Typically the GM-CSF and IL-9 are connected by a polymer linker, e.g., polypeptide. In certain embodiments, the disclosure relates to nucleic acids encoding these polypeptide conjugates, vectors comprising nucleic acid encoding polypeptide conjugates, and protein expression systems comprising these vectors such as infectious viral particles and host cells comprising such a nucleic acids.

Abstract: Treatment of lesions of pathological angiogenesis, especially tumors, rheumatoid arthritis, diabetic retinopathy, age-related muscular degeneration, and angiomas. A conjugate is used comprising a molecule that exerts a biocidal or cytotoxic effect on target cells in the lesions and an antibody directed against an extracellular matrix component which is present in such lesions. The antibody may be directed against fibronectin-2 (IL-2), doxorubicin, interleukin-12 (IL-12), Interferon-? (IFN-?), Tumor Necrosis Factor ? (TNF?) or Tissue Factor protein (which may be truncated).

Abstract: The present invention provides a method for producing a protein which has a restored native higher-order structure by bringing a protein which has lost its native higher-order structure into contact at pH 6.5 to 9.0 with a 1 to 3% aqueous solution of a specific surfactant, such as lauroylglutamic acid to obtain a solubilized solution of the protein; and then adding the solubilized solution to a buffer with pH 6.5 to 9.0 containing arginine or an arginine derivative at a concentration of 0.1 to 1.2 M to lower the concentration of the specific surfactant, such as lauroylglutamic acid, in the obtained mixture solution down to 0.02 to 0.275%. According to the present invention, it is possible to easily restore the native higher-order structure of a protein while smoothly removing the surfactant from the protein.

Abstract: Cytokine IFN? nucleic acids from the Cynomolgus monkey are useful for expression of IFN? proteins that are functional homologs of human IFN?. The nucleic acids and proteins produced therefrom are useful in screening and safety testing of IFN?, the generation and testing of IFN? modulators and related activities.

Abstract: The present invention provides methods and compositions for the preparation and delivery of chimeric cytokine proteins, including cell cultures, methods of purification and purified compositions.

Abstract: Provided herein are IL-2 muteins and IL-2 mutein Fc-fusion molecules that preferentially expand and activate T regulatory cells and are amenable to large scale production. Also provided herein are variant human IgG1 Fc molecules lacking or with highly reduced effector function and high stability despite lacking glycosylation at N297. Also, provided herein are linker peptides that are glycosylated when expressed in mammalian cells.

Abstract: The synergistic biomolecule-polymer conjugates are the long-acting, in vivo controlled continuous-release and hybrid synergy systems of biomolecules that provide increased biological activities and enhanced pharmacological properties for achieving greater therapeutic efficacies.