The USPTO has recently published several noteworthy patent applications related to cell-based assays for drug discovery or functional genomics applications:
Title: Surrogate cell-based system and method for assaying the activity of hepatitis C virus NS3 protease
Filed: May 27, 2005
Inventors: Charles Pellerin and Daniel Lamarre (Boehringer Ingelheim Canada)
According to its abstract, the patent application is for the development of a cell-based assay system having improved sensitivity to HCV NS3 protease activity when compared to known assays, which is useful for screening test compounds capable of modulating (particularly inhibiting) HCV NS3 protease activity. This system provides a first construct comprising a transactivator domain joined downstream of the NS3-5 domains of HCV under the control of a non-cytopathic viral promoter system. A second construct is also provided that comprises a reporter gene under the control of an operator sensitive to the binding of the transactivator. The NS3-5 domains encodes the NS3 polyprotein which comprises: the NS3 protease, followed by the NS4A co-factor, the NS4B and NS5A proteins (including any derivative, variant or fragment thereof, terminated by the NS5B protein (including any derivative, variant or fragment thereof) sufficient to constitute a NS5A/5B cleavage site. The transactivator, when expressed and released from the polyprotein, initiates transcription and expression of the reporter gene, which is measurable, the abstract states.
Title: Human adipocyte cell populations and methods for identifying modulators of same
Filed: May 31, 2005
Inventors: John Stevenson and James Kirkland (AdipoGenix)
According to its abstract, the patent application is for methods of obtaining high-yield, essentially pure human predipocyte cultures. Cultures obtained according to the instant methodology are also described, as are methods of identifying adipogenic modulatory agents, e.g., high-throughput screening assays, the abstract states.
Title: Optical interrogation system and method for 2-D sensor arrays
Filed: April 5, 2005
Inventors: Norman Fontaine, Eric Mozdy, and Po Kin Yuen (Corning)
According to its abstract, the patent application is for an optical interrogation system and method that can interrogate a 2D array of optical sensors (e.g., grating-coupled waveguide sensors) located in a 2D specimen plate (e.g., microplate). In one embodiment, the optical interrogation system has a launch system which directs an array of light beams towards the array of sensors in the two-dimensional specimen plate. The optical interrogation system also has a receive system that includes a Keplerian beam expander (used in reverse as a beam condenser) which receives an array of light beams from the array of sensors and directs each received light beam to a unique region on the detection plane of a small area detector (e.g., CCD camera). In addition, the optical interrogation system has a processor that analyzes changes in the position or shape of each detected light beam to determine if a binding event (bio-chemical interaction) or a mass transport (cell-based assay) occurred, or to determine the rate of binding (kinetics) that occurred on each sensor, the abstract states.
Title: Use of isogenic human cancer cells for high-throughput screening and drug discovery
Filed: June 23, 2005
Inventors: Christopher Torrance, Bert Vogelstein, and Kenneth Kinzler (Johns Hopkins University)
According to its abstract, the patent application is for a strategy for drug-screening based on cells that are isogenic except for a gene of interest. Each cell can be transfected with a vector that encodes a different fluorescent protein that can be differentially detected to monitor cell growth. Co-culture of both cells allows facile screening for compounds with selective toxicity towards a gene of interest. The drug screening is broadly applicable for mining therapeutic agents targeted to specific genetic alterations responsible for cancer development, the abstract states.
Title: Assay system for screening protease inhibitors
Filed: March 15, 2005
Inventors: Ting-Jen Cheng and Chen-Chen Kan (Keck Graduate Institute)
According to its abstract, the patent protects compositions and methods for identifying agents that inhibit protease activity. In particular, polynucleotides, recombinant expression vectors, and host cells are provided that may be used in a bacterial cell-based assay for identifying agents that are inhibitors of protease activity, such as inhibitors of HIV protease activity. The bacterial cells express a precursor of a protease and encode a reporter polypeptide that contains a protease recognition sequence, which can be cleaved by the mature, catalytically active protease such that the reporter activity of the reporter polypeptide is decreased or eliminated, the abstract states.
Title: Methods, compositions, and kits for analysis of enzyme activity in cells
Filed: Dec. 15, 2004
Inventors: Ronald Graham, Michael Sekar, and Maura Barbisin (Applera Corporation)
According to its abstract, the patent application is for methods for detecting an activity of an enzyme in a cell. In some embodiments, the methods include contacting a cell with a liposome containing at least one substrate, thereby facilitating introduction of the substrate into the cell. The substrate is capable of producing a detectable light signal when acted on by the enzyme, and the signal is detected. The methods can be used in screening agents that can inhibit or activate an enzyme activity. The methods can also be used in various downstream assays such the detection of interactions between intracellular proteins, screening for variants of an enzyme, and detection of various diseases. The patent application also describes compositions and kits for carrying out the various methods, the abstract states.
Title: Interpolated image response
Filed: Jan. 27, 2005
Inventors: Vance Faber and John Elling (Becton Dickinson)
According to its abstract, the patent application is for methods for characterizing a multidimensional distribution of responses from the objects in a population subject to a perturbation. The methods enable the creation of a "degree of response" scale interpolated from non-perturbed and perturbed reference populations. The methods enable, using the interpolated degree of response scale, the quantitation of a degree of response of a test compound subject to a given level of perturbation, and enables the generation of a dose-response curve for a test compound. The methods are useful in a wide range of applications, such as cellular analysis and high-content screening of compounds, as carried out in pharmaceutical research, the abstract states.