Antagonists of human proprotein convertase subtilisin-kexin type 9 (“PCSK9”) are disclosed. The disclosed antagonists are effective in the inhibition of PCSK9 function and, accordingly, present desirable antagonists for use in the treatment of conditions associated with PCSK9 activity. The present invention also discloses nucleic acid encoding said antagonists, vectors, host cells, and compositions comprising the antagonists. Methods of making PCSK9-specific antagonists as well as methods of using the antagonists for inhibiting or antagonizing PCSK9 function are also disclosed and form important additional aspects of the present disclosure.

1d05 pcsk9 antagonists

1b20 pcsk9 antagonists

The present invention provides compositions and methods for detecting the activation states of components of signal transduction pathways in tumor cells. Information on the activation states of components of signal transduction pathways derived from use of the invention can be used for cancer diagnosis, prognosis, and in the design of cancer treatments.

Drug selection for breast cancer therapy using antibody-based arrays

System, device and method for determining the concentration of an analyte

In one aspect, the present invention is directed to a glucose sensing device for implantation within subcutaneous tissue of an animal body. In one embodiment, the glucose sensing device includes a first chamber containing first magnetic particles and a hydrocolloid solution (for example, ConA-dextran hydrocolloid) wherein the first magnetic particles are dispersed in the hydrocolloid solution. In operation, glucose within the animal may enter and exit the first chamber and the hydrocolloid solution changes in response to the presence or concentration of glucose within the first chamber. The sensing device also includes a reference chamber containing second magnetic particles and a reference solution wherein the second magnetic particles are dispersed in the reference solution. The reference solution (for example, oil or alcohol compounds) includes a known or fixed viscosity. The reference solution may also be a hydrocolloid solution (for example, ConA-dextran hydrocolloid). The first and/or second magnetic particles may include amine-terminated particles, at least one rare earth element (for example, neodymium or samarium), and/or a ferromagnetic material.

Method and apparatus for analyte sensing

The present invention provides methods of screening for ligands of target molecules. The methods of the present invention include assays in which a target molecule is subjected to denaturing conditions, and compounds are screened for the ability to alter the susceptibility of the target to unfolding. The methods of the present invention use fluorescence detection to determine that degree of unfolding of a target molecule. In some aspects of the present invention, fluorescence resonance energy transfer (FRET) is detected. In other aspects of the invention, fluorescence polarization (FP) is detected. In preferred embodiments, a target molecule such as a target protein is heated to a temperature, called TATLAS, at which at least a portion of the target molecule unfolds, in the presence of a test compound. In some embodiments of the present invention, the degree of unfolding of the target molecule is determined by binding of a specific binding member specific for the unfolded form of a target molecule that is coupled to a fluorophore that can participate in FRET. In some other embodiments of the present invention, the degree of unfolding of a target molecule is determined by FRET detection of aggregates of the target molecule. In yet other embodiments of the present invention, the degree of unfolding of a target molecule is determined by detection of fluorescence polarization of aggregates of the target molecule. The present invention provides sensitive, high throughput screens for identifying ligands of target molecules that are not dependent on the identity or function of the target.

Methods of screening for ligands of target molecules

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Methods of screening for ligands of target molecules