Abstract: The invention provides methods and compositions for treating conditions mediated by various kinases wherein derivatives of urea compounds are employed. The invention also provides methods of using the compounds and/or compositions in the treatment of a variety of diseases and unwanted conditions in subjects.

Abstract: The present application provides a method for treating Pompe disease in a subject in need thereof, that includes a method of administering to the subject a GAA enzyme in combination with an ASSC for the GAA enzyme. The present application also provides methods for increasing the in vitro and in vivo stability of a GAA enzyme formulation.

Abstract: The method for modeling a dosing regimen for a medicament includes providing a system having at least two biocompartments. The method determines steady state levels in each of the biocompartments. After that, the method provides for modifying values to calculate an amount of at least one protein in one of the biocompartments to which the protein is being transported. Next, the method calculates and integrates a weighted value of the protein to find a weighted area under the curve. Then, the method calculates and integrates a non-drug value of the protein to find a non-drug area under the curve. Finally, the method evaluates one or more dosing regimens by comparing the weighted area under the curve and the non-drug area under the curve of the protein to determine a net effect of the drug over the time period.

Abstract: Provided herein are linker compounds and conjugates that include the linker compounds. In one embodiment, the linker compounds comprise 2 or 3 residues of 6-aminohexanoic acid and optionally 7-10 residues of polyethyleneglycol (PEG). The linker compounds are useful in forming conjugates with one or more components useful in biopharmaceutical or bioanalytical applications. In particular, the biopharmaceutically useful compounds are kinase inhibitors. The conjugates described herein have utility in a variety of diagnostic, separation, and therapeutic applications.

Abstract: Novel means and methods for analyzing hybridization data derived from hybridization assays between a target nucleic acid and differently sequenced polynucleotide probes involve selecting probe sets that define reference sequences for sequence signatures and deriving useful data about the nature of the target nucleic acid molecule based on its hybridization to the probes. The methods are useful for determining whether the target contains a nucleic acid or polypeptide sequence signature, whether the target encodes a member of a gene family, or whether the target is derived from one of any number of genes.

Abstract: The present invention provides an advance in phage display technology by permitting the uncoupling of the propagation of phages containing inserted sequences encoding heterologous polypeptides from the expression of said polypeptides. The invention provides phage constructs and methods for their use to permit phage coat protein expression, and thus phage propagation, in the absence of display of heterologous polypeptides, which may be expressed as a fusion with said coat protein in a regulated manner.

Abstract: The invention provides an affinity filter for the binding of phage-displayed proteins to dissolved target molecules. The phage-displayed proteins are contacted with immobilized target in the presence and absence of dissolved target; the behavior of the phage-displayed proteins as a function of concentration of dissolved target permits approximation of the affinity of the phage-displayed protein for target. The invention also provides a method to screen large numbers of compounds for their ability to compete with a compound known to bind a phage-displayed protein.

Abstract: Novel means and methods for analyzing hybridization data derived from hybridization assays between a target nucleic acid and differently sequenced polynucleotide probes involve selecting probe sets that define reference sequences for sequence signatures and deriving useful data about the nature of the target nucleic acid molecule based on its hybridization to the probes. The methods are useful for determining whether the target contains a nucleic acid or polypeptide sequence signature, whether the target encodes a member of a gene family, or whether the target is derived from one of any number of genes.

Abstract: The invention provides pyrrole-containing compounds and methods of use thereof. Kits and pharmaceutical compositions comprising the pyrrole compounds of the invention are also provided. The compounds and compositions disclosed herein are preferably used in the treatment of neurodegenerative diseases, cardiovascular diseases, proliferative diseases, and visual disorders. In particular, methods and compositions for the treatment of stroke are disclosed herein.

Abstract: Novel means and methods for analyzing hybridization data derived from hybridization assays between a target nucleic acid and differently sequenced polynucleotide probes involve selecting probe sets that define reference sequences for sequence signatures and deriving useful data about the nature of the target nucleic acid molecule based on its hybridization to the probes. The methods are useful for determining whether the target contains a nucleic acid or polypeptide sequence signature, whether the target encodes a member of a gene family, or whether the target is derived from one of any number of genes.

Abstract: The present invention provides an advance in phage display technology by permitting the uncoupling of the propagation of phages containing inserted sequences encoding heterologous polypeptides from the expression of said polypeptides. The invention provides phage constructs and methods for their use to permit phage coat protein expression, and thus phage propagation, in the absence of display of heterologous polypeptides, which may be expressed as a fusion with said coat protein in a regulated manner.

Abstract: Methods for testing oligonucleotide arrays are disclosed including methods for testing the efficiency of nucleotide coupling; methods for testing amounts of deprotected oligonucleotides; methods for determining amounts of depurinated oligonucleotides; and methods of detecting the presence of cleavable structural features, such as double-stranded nucleic acids.

Abstract: Methods for discriminating between fully complementary hybrids and those that differ by one or more base pairs and libraries of unimolecular, double-stranded oligonucleotides on a solid support. In one embodiment, the present invention provides methods of using nuclease treatment to improve the quality of hybridization signals on high density oligonucleotide arrays. In another embodiment, the present invention provides methods of using ligation reactions to improve the quality of hybridization signals on high density oligonucleotide arrays. In yet another embodiment, the present invention provides libraries of unimolecular or intermolecular, double-stranded oligonucleotides on a solid support. These libraries are useful in pharmaceutical discovery for the screening of numerous biological samples for specific interactions between the double-stranded oligonucleotides, and peptides, proteins, drugs and RNA.

Abstract: This invention provides methods of monitoring the expression levels of a multiplicity of genes. The methods involve hybridizing a nucleic acid sample to a high density array of oligonucleotide probes where the high density array contains oligonucleotide probes complementary to subsequences of target nucleic acids in the nucleic acid sample.

Abstract: The invention provides pyrrole-containing compounds and methods of use thereof. Kits and pharmaceutical compositions comprising the pyrrole compounds of the invention are also provided. The compounds and compositions disclosed herein are preferably used in the treatment of neurodegenerative diseases, cardiovascular diseases, proliferative diseases, and visual disorders. In particular, methods and compositions for the treatment of stroke are disclosed herein.

Abstract: Libraries of unimolecular, double-stranded oligonucleotides on a solid support. These libraries are useful in pharmaceutical discovery for the screening of numerous biological samples for specific interactions between the double-stranded oligonucleotides, and peptides, proteins, drugs and RNA. In a related aspect, the present invention provides libraries of conformationally restricted probes on a solid support. The probes are restricted in their movement and flexibility using double-stranded oligonucleotides as scaffolding. The probes are also useful in various screening procedures associated with drug discovery and diagnosis. The present invention further provides methods for the preparation and screening of the above libraries.

Abstract: The invention provides compounds having the imidazole, oxazole, or thiazole skeleton and uses thereof. The compounds described herein bind to phosphodiesterase 6D. The compounds disclosed herein can be used to modulate the activity of phosphodiesterase 6. The invention provides methods of using the compounds and/or compositions in the treatment of a variety of diseases and unwanted conditions in subjects. Kits comprising the compounds of the invention are also provided.

Abstract: The invention provides derivatives of statin compounds, preferably with reduced, or unappreciable, inhibitory activity against HMG-CoA reductase as well as compositions comprising such compounds. The invention also provides methods of using the compounds and/or compositions in the treatment of a variety of diseases and unwanted conditions in subjects. Kits comprising the non-statin compounds of the invention are also provided.

Abstract: The invention provides compounds having the thiophene or furan skeleton and uses thereof. The invention provides methods of using the compounds and/or compositions in the treatment of a variety of diseases and unwanted conditions in subjects. Kits comprising the compounds of the invention are also provided. The compounds and compositions disclosed herein are preferably used in the treatment of neurodegenerative diseases, cardiovascular diseases, proliferative diseases, and visual disorders. In particular, methods and compositions for the treatment of stroke are disclosed herein.

Abstract: The invention provides nucleic acid sequences which are complementary, in one embodiment, to a wide variety of murine genes. The invention provides the sequences in such a way as to make them available for a variety of analyses. As such, the invention related to diverse fields impacted by the nature of molecular interaction, including chemistry, biology, medicine, and medical diagnostics.