Abstract: A CCI-779 oral dosage form is provided in which, after oral administration to a subject, the CCI-779 has a whole blood peak concentration (Cmax) of 5.4±1.8 ng/mL and an area under the curve (AUC) of about 66± about 22 ng-hr/ml and the sirolimus has a Cmax of 18.7±9.6 ng/mL and an AUC of about 600± about 228 ng-hr/ml, for a 25 mg unit dose of CCI-779. Another CCI-779 oral dosage form is provided which, after oral administration thereof to a subject, the CCI-779 has a Cmax of 5.7±1.7 ng/mL and an AUC of about 60± about 20 ng-hr/ml and the sirolimus has a Cmax of 17.1±8.1 ng/mL and an AUC of about 548± about 187 ng-hr/ml in whole blood, for a 25 mg unit dose of CCI-779. Products containing these oral dosage forms, and methods of use thereof, are also described.

Abstract: Protein formulations and methods for reducing the viscosity of a protein formulation are provided. The method for reducing the viscosity of a protein formulation comprises adding a viscosity reducing agent, such as calcium chloride or magnesium chloride to the protein formulation.

Abstract: The present invention is directed to dihydrobenzofuranyl derivatives of formula I: or a pharmaceutically acceptable salt thereof, which are monoamine reuptake inhibitors, compositions containing these derivatives, and methods of their use for the prevention and treatment of conditions, including, inter alia, vasomotor symptoms sexual dysfunction, gastrointestinal disorders and genitourinary disorder, depression disorders, endogenous behavioral disorder, cognitive disorder, diabetic neuropathy, pain, and other diseases or disorders.

Abstract: The present invention is directed to substituted aryl cycloalkanoyl derivatives, compositions containing these derivatives, and methods of their use for the prevention and treatment of conditions ameliorated by monoamine reuptake including, inter alia, vasomotor symptoms (VMS), sexual dysfunction, gastrointestinal and genitourinary disorders, chronic fatigue syndrome, fibromyalgia syndrome, nervous system disorders, and combinations thereof, particularly those conditions selected from the group consisting of major depressive disorder, vasomotor symptoms, stress and urge urinary incontinence, fibromyalgia, pain, diabetic neuropathy, and combinations thereof.

Abstract: This invention provides compositions, organisms and methodologies employing a novel human protein kinase, MCRK1. The novel human kinase has sequence homology to rat myotonic dystrophy kinase-related Cdc42 binding kinase (MRCK) alpha. The gene encoding the novel kinase is localized in locus 11q13 of human chromosome 11. The novel protein kinase comprises multiple functional/structural domains that include a kinase domain, a pkinase_C domain, a DAG-PE binding domain, and a CNH domain. The sequence and structure similarity between the novel human protein and rat MRCK alpha indicates that the novel human protein may function as a downstream effector of Cdc42 in cytoskeleton reorganization.

Abstract: The present invention relates to methods of treating ADAMTS-5-associated diseases and particularly osteoarthritis comprising administering an agent capable of modulating ADMATS-5 activity to a subject afflicted with the disease. The agent is preferably a biaryl sulfonamide compound. The invention is based, in part, on the discovery that transgenic animals that do not express functional ADAMTS-5 show a reduction in the degree of osteoarthritis after the induction of osteoarthritis as compared to WT animals. Furthermore, the ADAMTS-5 transgenic animals have reduced aggrecanase activity in articular tissue as compared to WT animals. These animals are good models for ADAMTS-5-associated diseases, and for screening of drugs useful in the treatment and/or prevention of these diseases. There are no other animal models in which the deletion of the activity of a single gene is capable of abrogating the course of osteoarthritis.

Abstract: Protein formulations and methods for reducing the viscosity of a protein formulation are provided. The method for reducing the viscosity of a protein formulation comprises adding a viscosity reducing agent, such as calcium chloride or magnesium chloride to the protein formulation.

Abstract: The invention provides compounds of formula (I): wherein E, A, B?, R6, R7, R8, and R9 are defined in the specification which compounds exhibit anticancer activity and are useful for treating cancer.

Abstract: The present invention is directed to an anhydrate crystal form (designated as Form E herein) of 2-(3-fluoro-4-hydroxyphenyl)-7-vinyl-1,3-benzoxazol-5-ol, an estrogenic receptor modulator useful in the treatment of, for example, diseases related to abnormal levels of estrogen.

Abstract: The present invention is directed to methods of producing conjugates of A? peptide immunogens with protein/polypeptide carrier molecules, which are useful as immunogens, wherein peptide immunogens are conjugated to protein carriers via activated functional groups on amino acid residues of the carrier or of the optionally attached linker molecule, and wherein any unconjugated reactive functional groups on amino acid residues are inactivated via capping, thus retaining the immunological functionality of the carrier molecule, but reducing the propensity for undesirable reactions that could render the conjugate less safe or effective. Furthermore, the invention also relates to such immunogenic products and immunogenic compositions containing such immunogenic products made by such methods.

Abstract: Processes are disclosed for preparing indolinone phenylaminopropanol derivatives, particularly chiral indolinone phenylaminopropanol derivatives of the general formula: The processes disclosed may be used to prepare, inter alia, 7-fluoro-1-[(1S, 2R)-1-(3-fluorophenyl)-2-hydroxy-3-(methylamino)propyl]-3,3-dimethyl-1,3-dihydro-2H-indol-2-one and 7-fluoro-1-[(1S, 2R)-1-(3,5-difluorophenyl)-2-hydroxy-3-(methylamino)propyl]-3,3-dimethyl-1,3-dihydro-2H-indol-2-one. Intermediates of the processes are also disclosed.

Abstract: The present invention relates to Dibenzonaphthyridine Derivatives, compositions comprising an effective amount of a Dibenzonaphthyridine Derivative and methods for treating or preventing a proliferative disorder, comprising administering to a subject in need thereof an effective amount of a Dibenzonaphthyridine Derivative.

Abstract: The present invention relates to a compound of the formula: or an enantiomer, diastereomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, useful as modulators of 5-HT1A receptor activity and/or serotonin reuptake. These compounds are useful in treating nervous system disorders, such as anxiety-related disorders, cognition-related disorders, depression, schizophrenia, or sexual dysfunction and related illnesses.

Abstract: The present invention provides synthetic processes for the preparation of mono-sulfated derivatives of substituted benzoxazoles, which are useful as estrogenic agents.

Abstract: This invention provides progesterone receptor modulators having the structure: wherein R1 to R7, X, and Q are as defined in the specification; or a pharmaceutically acceptable salt thereof.

Abstract: The present invention is directed to a hydrate crystal form (designated as Form F herein) of 2-(3-fluoro-4-hydroxyphenyl)-7-vinyl-1,3-benzoxazol-5-ol, an estrogenic receptor modulator useful in the treatment of, for example, diseases related to abnormal levels of estrogen.

Abstract: Methods for detecting the presence or amount of Interleukin-12 (IL-12), particularly human IL-12, or antibodies that neutralize the activity of human IL-12 in a human biological sample, involve incubating the biological sample with an NK cell line or progeny thereof. A correlation is determined between the presence or amount of IL-12 (or anti-IL-12 antibodies) in the sample and the amount of gamma interferon (or a precursor activation factor or cytokine) secreted by the NK cells. For measuring antibodies, the sample is pre-incubated with IL-12. Levels of a cytokine or activation factor, such as IFN-?, secreted by the NK cells when in the presence of IL-12 are then compared with a control level of the cytokine or activation factor secreted by the NK cells or progeny thereof in the presence of a known amount of IL-12 and without the biological sample. The presence of IL-12 or neutralizing anti-IL12 antibodies in the sample is indicated by a variation, e.g.

Abstract: The present invention provides synthetic processes for the preparation of mono-sulfated derivatives of substituted benzoxazoles, which are useful as estrogenic agents.

Abstract: The present invention provides a method for inhibiting mannitol-induced aggregation of a protein in a liquid formulation by increasing the protein concentration to an amount greater than 50 mg/ml. The present invention also provides methods for storing and preparing a liquid formulation containing mannitol and a protein concentration greater than 50 mg/ml.

Abstract: This invention provides the use of a combination of CCI-779 and EKB-569 in the treatment of neoplasms.