Abstract: The present invention provides a polynucleotide vector system used during polypeptide display that can be used to facilitate transfer of pools of polynucleotides encoding antigen binding proteins of interest. The present invention also provides methods that allow seamless conversion of pools of polynucleotides encoding antigen binding proteins using a restriction enzyme digestion and ligation strategy.

Abstract: The present invention provides VEGF binding peptides. In addition, the invention provides VEGF peptides conjugated to antibodies alone and in conjunction with other anti-angiogenic molecules. Various uses of the peptides and compounds are provided, including methods to treat disorders associated with abnormal angiogenesis.

Abstract: The present invention provides AA targeting compounds which comprise AA targeting agent-linker conjugates which are linked to a combining site of an antibody. Various uses of the compounds are provided, including methods to treat disorders connected to abnormal angiogenesis.

Abstract: This invention relates to methods for rationally designing cell culture media for use in cell cultures, e.g., cell cultures employed in polypeptide production; cell culture media designed with the disclosed methods; methods of producing a polypeptide of interest, e.g., an antibody, using such media; polypeptides produced using the methods and media disclosed herein; and pharmaceuticals compositions containing such polypeptides. The rationally designed media contain a concentration of an amino acid that is calculated for use in cell mass, a concentration of the amino acid that is calculated for use in cell maintenance, and a concentration of the amino acid that is calculated for incorporation into the polypeptide of interest.

Abstract: The invention features methods and compositions for preventing or treating bone cancer pain including cancer pain associated with bone metastasis by administering an antagonist of nerve growth factor (NGF). The NGF antagonist may be an anti-NGF (such as anti-hNGF) antibody that is capable of binding hNGF.

Abstract: An improved system for large scale production of proteins and/or polypeptides in cell culture is provided. In accordance with the present invention, cells expressing the protein or polypeptide of interest are grown in media that comprise a glycolysis-inhibiting substance. Additionally and/or alternatively, cells expressing the protein or polypeptide of interest are grown in media in which glutamine is limited. The use of such a system allows high levels of protein or polypeptide production and lessens accumulation of undesirable metabolic waste products such as lactate. Proteins and polypeptides expressed in accordance with the present invention may be advantageously used in the preparation of pharmaceutical, immunogenic, agricultural or other commercial compositions.

Abstract: The invention relates to systems and methods for producing proteins of interest. The invention employs genetically-engineered animal or plant cells that have modified protein folding or processing capacities. In one aspect, the invention features genetically-engineered cells comprising one or more recombinant expression cassettes which encode (1) a protein of interest and (2) a polypeptide that is functional in the unfolded protein response (UPR) pathway of the cells. Co-expression of the polypeptide significantly increases the yield of the protein of interest in the genetically-engineered cells. In one example, the genetically-engineered cells are animal cells, and the co-expressed polypeptide is a component or modulator of an XB1- or ATF6-mediated UPR pathway.

Abstract: The present invention relates to methods for the control of virulence of infectious bacteria by modulating the extra-cellular concentration of bacterial cell signalling molecules. Derivatives of cell signalling molecules are conjugated to suitable carrier proteins and used to isolate high affinity receptors recognizing the native signal molecule(s). By binding to signalling molecules, the receptors reduce and maintain extra-cellular concentrations of signal molecules below the threshold level that would otherwise result in certain opportunistic pathogens adopting a virulent form, and can transform virulent organisms to non-virulent states. These receptors have applications for the treatment of individuals with susceptibility to infection, the treatment of patients with existing infections, in disease monitoring and management, and in related applications where the host for infection is an animal or plant.

Abstract: Pharmaceutical compositions containing modified fusion proteins of transferrin and therapeutic proteins or peptides with increased serum half-life or increased serum stability are disclosed. Preferred fusion proteins include those modified so that the transferrin moiety exhibits no or reduced glycosylation, but does exhibit binding to iron and/or the transferrin receptor. Such fusion proteins may be administered orally.

Abstract: An improved system for large scale production of glycoproteins in cell culture is provided. In accordance with the present invention, cells expressing a glycoprotein are grown in media that contain manganese at a concentration of between approximately 10 and 600 nM. The use of such a system allows production of a glycoprotein with an increased glycosylation pattern and/or a glycosylation pattern that more accurately reflects the glycosylation pattern of the naturally occurring glycoprotein. A glycoprotein expressed in accordance with the present invention may be advantageously used in the preparation of pharmaceutical compositions.

Abstract: The present invention provides antagonizing antibodies, antigen-binding portions thereof, and aptamers that bind to proprotein convertase subtilisin kexin type 9 (PCSK9). Also provided are antibodies directed to peptides, in which the antibodies bind to PCSK9. The invention further provides a method of obtaining such antibodies and antibody-encoding nucleic acid. The invention further relates to therapeutic methods for use of these antibodies and antigen-binding portions thereof to reduce LDL-cholesterol levels and/or for the treatment and/or prevention of cardiovascular disease, including treatment of hypercholesterolemia.

Abstract: The present invention features methods for treating or preventing pain comprising administering an amount of a nerve growth factor antagonist (such as an anti-NGF antibody) and an amount of an NSAID such that together they provide effective pain relief. The invention also features compositions comprising a nerve growth factor antagonist and an NSAID and kits containing the same.

Abstract: Monoclonal antibody 9TL and antibodies derived from 9TL directed against amyloid-beta peptide and methods of using same for diagnosing and treatment of Alzheimer's disease and A? peptide associated diseases are described. Methods of using antibodies directed against amyloid-beta peptide having impaired effector function for treatment of Alzheimer's disease and A? peptide associated diseases are also described.

Abstract: The present invention provides non-steroidal compounds of formula I which are selective modulators (i.e., agonists and antagonists) of a steroid receptor, specifically, the glucocorticoid receptor. The present invention also provides pharmaceutical compositions containing these compounds and methods for using these compounds to treat animals requiring glucocorticoid receptor agonist or antagonist therapy. Glucocorticoid receptor modulators are useful to the diseases, such as obesity, diabetes, inflammation and others as described below. The present invention also provides intermediates and processes for preparing these compounds.

Abstract: The present invention relates to crystalline forms of (3S)-3-[N—(N?-(2-tert-butylphenyl)oxamyl)alaninyl]amino-5-(2?,3?,5?,6?-tetrafluorophenoxy)-4-oxopentanoic acid (see formula I). The invention further relates to pharmaceutical compositions comprising such crystalline forms and to the use of said pharmaceutical compositions and said crystalline forms in the treatment of various conditions, particularly in the treatment of liver fibrosis.

Abstract: The present invention provides benzamide inhibitors of the P2X7 receptor of the formula: wherein R1-R3 are as defined herein. The compounds of the invention are useful in the treatment of IL-1 mediated disorders, including, without limitation, inflammatory diseases such as osteoarthritis and rheumatoid arthritis; allergies, asthma, COPD, cancer, reperfusion or ischemia in stroke or heart attack, autoimmune diseases and other disorders.

Abstract: The present invention relates to novel pyridazinone compounds, pharmaceutical compositions comprising those compounds and to methods of using such compounds and compositions to inhibit aldose reductase, lower sorbitol levels and, thus, lower fructose levels, and/or treat or prevent diabetic complications such as diabetic neuropathy, diabetic retinopathy, diabetic nephropathy, diabetic cardiomyopathy, diabetic microangiopathy and diabetic macroangiopathy in mammals. This invention also relates to methods of affording cardioprotection to subjects not suffering from diabetes. This invention also relates to pharmaceutical compositions and kits comprising a combination of an aldose reductase inhibitor (ARI) of this invention and a sorbitol dehydrogenase inhibitor and to methods of using such compositions or kits to treat or prevent the above diabetic complications in mammals.

Abstract: The invention relates to indole derivatives and to processes for the preparation of, intermediates used in the preparation of, compositions containing and the uses of, such derivatives. The indole derivatives according to the present invention are useful in numerous diseases, disorders and conditions, in particular inflammatory, allergic and respiratory diseases, disorders and conditions.

Abstract: The invention relates to indole derivatives and to processes for the preparation of, intermediates used in the preparation of, compositions containing and the uses of, such derivatives. The indole derivatives according to the present invention are useful in numerous diseases, disorders and conditions, in particular inflammatory, allergic and respiratory diseases, disorders and conditions.

Abstract: The invention features a method for treating chronic pain using a compound of formula (I).