Abstract: Disclosed are anti-5T4 antibody drug conjugates and methods for preparing and using the same.

Abstract: The present invention broadly relates to the synergistic attenuation of vesicular stomatitis virus (VSV). More particularly, the invention relates to the identification of combined mutation classes which synergistically attenuate the pathogenicity of VSV vectors in mammals and immunogenic compositions thereof.

Abstract: Anti-IL-17 antibodies are identified that are characterized as having a high affinity and slow off rate for human IL-17. The antibodies of the invention may be chimeric, humanized or fully human antibodies, immunoconjugates of the antibodies or antigen-binding fragments thereof. The antibodies of the invention are useful in particular for treating autoimmune, inflammatory, cell proliferative and developmental disorders.

Abstract: The present invention relates to novel muteins of human fibroblast growth factor 21 with reduced deamidation compared to wild-type human FGF-21. Both protein and the respective encoding nucleic acid species are disclosed. The invention also embodies vectors and host cells for the propagation of said nucleic acid sequences and the production of said muteins. Also disclosed are methods for treating type 2 diabetes, obesity, or metabolic syndrome.

Abstract: The present invention relates to novel muteins of human fibroblast growth factor-21 with reduced susceptibility for proteolytic degradation when expressed in yeast. Both protein and the respective encoding nucleic acid species are disclosed. The invention also embodies vectors and host cells for the propagation of said nucleic acid sequences and the production of said muteins. Also disclosed are methods for treating type 2 diabetes, obesity, or metabolic syndrome.

Abstract: The present invention relates to novel muteins of human fibroblast growth factor 21 with reduced capacity of O-glycosylation when expressed in yeast compared to wild-type human FGF-21. Both protein and the respective encoding nucleic acid species are disclosed. The invention also embodies vectors and host cells for the propagation of said nucleic acid sequences and the production of said muteins. Also disclosed are methods for treating type 2 diabetes, obesity, or metabolic syndrome.

Abstract: The invention provides specific FGF-21 compounds fused to specific IgG4-Fc or HSA derivatives resulting in fusion proteins that are biologically active with an extended elimination half-life and a slower clearance. These FGF-21 compound fusion proteins and compositions are useful in treating type 2 diabetes, obesity, and metabolic syndrome.

Abstract: The present invention encompasses isolated antibodies, or antigen-binding portions thereof, that specifically bind mature human IL-1 Beta. These antibodies, or antigen-binding portions thereof, generally exhibit high binding affinities (low kooff values), reduced deamidation compared to the native antibody, and can be used to treat various diseases such as rheumatoid arthritis, osteoarthritis, or neuroinflammation.

Abstract: The present invention relates to novel muteins of human fibroblast growth factor 21 with improved pharmaceutical properties. Both protein and the respective encoding nucleic acid species are disclosed. The invention also embodies vectors and host cells for the propagation of said nucleic acid sequences and the production of said muteins. Also disclosed are methods for treating type 2 diabetes, obesity, metabolic syndrome, and in reducing the mortality and morbidity of critically ill patients.

Abstract: Method of treating a disease or pathological condition with activated protein C or a compound having activated protein C activity by direct regulation of the expression of specific genes associated with the disease or pathological condition.

Abstract: The present invention relates to insoluble compositions comprising a protein selected from the group consisting of insulin, insulin analogs, and proinsulins; a derivatized protein selected from the group consisting of derivatized insulin, derivatized insulin analog, and derivatized proinsulin; a complexing compound; a hexamer-stabilizing compound; and a divalent metal cation. Formulations of the insoluble composition are suitable for both parenteral and non-parenteral delivery for treating hyperglycemia and diabetes. Microcrystal forms of the insoluble precipitate are pharmaceutically analogous to the neutral protamine Hagedorn (NPH) insulin crystal form. Surprisingly, it has been discovered that suspension formulations of such insoluble compositions possess unique and controllable dissolution properties that provide therapeutically advantageous glucodynamics compared with insulin NPH formulations.

Abstract: Fatty acid-acylated insulin analogs are soluble at moderately acidic pH and provide long-acting basal control of glucose levels. In such a molecule, the insulin analog portion comprises an insulin A-chain, or an analog thereof, properly cross-linked to an analog of the insulin B-chain, wherein the &egr;-amino group of a Lys residue at either positions 28 or 29 of the B-chain analog is acylated with a fatty acid. The insulin analog portion of the molecules comprises an A-chain of insulin, or an analog thereof, with an optional Arg at position 0, properly cross-linked to a B-chain analog that includes Arg at positions 31 and 32.

Abstract: The invention relates to a method of administering a fatty acid-acylated insulin or insulin analog by inhalation, a method for treating diabetes by administering a fatty acid-acylated insulin or insulin analog by inhalation, and a method for treating hyperglycemia by administering a fatty acid-acylated insulin or insulin analog by inhalation.

Abstract: The present invention is a method of using the BK enhancer in tandem with a eukaryotic promoter to promote transcription of DNA that encodes a useful substance. The method of the present invention requires the presence of the E1A gene product for maximum expression of the useful substance. The present invention also comprises a number of useful expression vectors that comprise the BK enhancer in tandem with the adenovirus 2 late promoter positioned to drive expression of a variety of proteins, such as protein C, chloramphenicol acetyltransferase, and tissue plasminogen activator. The present invention further comprises a method for increasing the activity of the BK enhancer involving placement of the BK enhancer immediately upstream of the eukaryotic promoter used in tandem with the BK enhancer to drive expression of a useful substance. Furthermore, the present invention also comprises a method for coamplification of genes in primate cells.

Abstract: The present invention provides a method of treatment for patients with a variety of thrombotic disorders including, but not limited to, stroke, venous thrombosis, myocardial infarction, unstable angina, abrupt closure following angioplasty or stent placement, and thrombosis as a result of peripheral vascular surgery. Said treatment is a combination therapy with human aPC and antiplatelet agents including, but not limited to, aspirin (ASA), clopidogrel, ReoPro.RTM. (abciximab), dipyridamole, ticlopidine and IIb/IIIa receptor antagonists. The synergy will result in the ability to reduce the dosages of the agents used in the combination therapy.

Abstract: The present invention is a method of using the BK enhancer in tandem with a eukaryotic promoter to promote transcription of DNA that encodes a useful substance. The method of the present invention requires the presence of the E1A gene product for maximum expression of the useful substance. The present invention also comprises a number of useful expression vectors that comprise the BK enhancer in tandem with the adenovirus 2 late promoter positioned to drive expression of a variety of proteins, such as protein C, chloramphenicol acetyltransferase, and tissue plasminogen activator. The present invention further comprises a method for increasing the activity of the BK enhancer involving placement of the BK enhancer immediately upstream of the eukaryotic promoter used in tandem with the BK enhancer to drive expression of a useful substance. Furthermore, the present invention also comprises a method for coamplification of genes in primate cells.

Abstract: A method of treatment for patients with vascular occlusion and thromboembolic disorders including the acquired disease state of thrombotic stroke, by administering activated protein C. The administration of aPC provides a highly selective therapeutic agent with a low potential for causing bleeding complications. The administration of aPC is beneficial in preventing the local extension of the microvascular and macrovascular occluding arterial thrombus, thereby reducing the neurological deficit resulting from the stroke.