Abstract: The instant invention provides a method of treating a cancer selected from the group consisting of non-small cell lung cancer and breast cancer with an mTOR inhibitor and an ?v62 3 integrin antagonist, wherein the mTOR inhibitor is ridaforolimus, everolimus, temsirolimus or a combination thereof.

Abstract: The invention relates generally to methods for purifying a Fc-fusion protein produced in a eukaryotic expression system. More specifically, the invention provides a robust and scalable downstream purification process suitable for use in manufacturing TNFR:Fc for human administration which comprises an optimized Protein A affinity chromatography step and two ion exchange chromatography steps both of which are operated in the bind-and-elute mode.

Abstract: Methods and associated compositions of matter (e.g., kits, cell lines, etc.) for screening compounds that bind to macrophase mannose receptor (MMR). Compounds identified by these methods and drug conjugates that includes these compounds are also encompassed as are their uses in the manufacture of medicaments.

Abstract: The invention herein is directed to a selective A? oligomer immunoassay capable of reliably and sensitively detecting A? oligomers in a biological sample of a patient. In one embodiment the inventive assay uses a pair of anti-AP oligomer antibodies, 19.3 and 82E1, to detect and quantify A? oligomers in a cerebrospinal fluid (CSF) sample. The inventive assay can be used to differentiate Alzheimer's disease (AD) patients from non-AD patients and/or to stratify AD patients according to the severity of their disease. The inventive assay can also be used as a target engagement assay that can measure bound A? oligomers as a surrogate end-point for the assessment of therapeutic efficacy and/or target engagement.

Abstract: The present invention relates to a process for the selective enzymatic hydrolysis of C-terminal esters of peptide substrates in the synthesis of peptides, comprising hydrolysing C-terminal tert-butyl esters using the protease subtilisin. This process is useful in the production of protected or unprotected peptides.

Abstract: Compositions comprising granulocyte-colony stimulating factor (GCSF) produced in a strain of Pichia pastoris glycoengineered to produce a GCSF wherein greater than 18% of the molecules comprise an 0-glycan with one mannose per (0-glycan is described. In particular aspects, the GCSF is PEGylated at the JV-terminus.

Abstract: Antibodies specific for Dkk-1, an inhibitor of the osteoanabolic Wnt/LRP5 signaling pathway, are described. The antibodies, which inhibit binding of Dkk-1 to LRP5, are useful in compositions for stimulating bone growth, in particular, compositions for treating bone disorders which result in a loss in bone, for example, osteoporosis.

Abstract: In its many embodiments, the present invention discloses novel compounds, as inhibitors of HDM2 protein methods for preparing such compounds, pharmaceutical compositions including one or more such compounds, methods of treatment, prevention, inhibition, of one or more diseases associated with the HDM2 protein or P53 using such compounds or pharmaceutical compositions.

Abstract: The present invention is directed to quinazolinone compounds which are antagonists of T-type calcium channels, and which are useful in the treatment or prevention of disorders and diseases in which T-type calcium channels are involved. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which T-type calcium channels are involved.

Abstract: Disclosed are 2-aza-substituted 1-carbadethiapen-2-em-3-carboxylic acids. I, where the generic 2-aza group includes azido, acylamino, amino, alkylamino, dialkylamino, triazolyl, triazolinyl, aziridinyl, and their pharmaceutically acceptable salt, ester, anhydride and amide derivatives which are useful as antibiotics. Also disclosed are processes for the preparation of I from the known, appropriately substituted bicyclic keto ester II via the 2-azido central intermediate III: ##STR1## wherein R.sup.16 is H or CH.sub.3, preferably beta-methyl; R.sup.6, and R.sup.7 are independently hydrogen, linear, branched or cyclic C.sub.1 -C.sub.5 alkyl, which can be substituted with fluoro, hydroxy, protected hydroxy, sulfoxy, amino, protected amino, wherein R.sup.6 and R.sup.7 taken together can also be C.sub.2 -C.sub.4 alkylidene, similarly substituted; with the proviso that both R.sup.6 and R.sup.7 are not unsubstituted alkyl, R.sup.1 and R.sup.

Abstract: Carbapenems having the formula: ##STR1## In which Q.sup.+ is quinolinium or isoquinolinium, are useful antibacterial agents.