Abstract: A cell-based binning method (“Data Driven” binning method) allows the inclusion of all molecules, generates a high percentage of occupied cells, and provides adequate division of the molecules in the low-dimensional subspaces (typically all one-dimension (1-D), two-dimension (2-D), and three-dimension (3-D) subspaces). A chemical space coverage criterion (“Uniform Cell Coverage (UCC)” criterion) measures the uniformity of coverage of the molecules selected. A fast exchange design algorithm (“fast exchange UCC” algorithm) that minimizes the number of searches of the candidate points while maximizing the number of exchanges during each pass through the candidate points. This method is many times faster than previous exchange algorithms and generates designs with good coverage properties.
Type:
Grant
Filed:
May 4, 2000
Date of Patent:
February 1, 2005
Assignee:
Smithkline Beecham Corporation
Inventors:
Raymond L. H. Lam, William J. Welch, Sidney Stanley Young
Abstract: Novel DNA constructs and host cells comprising the same are disclosed. DNA constructs comprise a transcription unit (e.g. operon) comprising DNA sequences encoding for ribonucleotide reductase and thioredoxin or a uridine kinase gene and/or a dCTP deaminase gene. In preferred embodiments the constructs comprising DNA sequences encoding for ribonucleotide reductase and thioredoxin further comprise DNA sequences encoding for thymidylate synthase and/or transcription units comprising sequences encoding for uridine kinase preferably together with dCTP deaminase. In particularly preferred embodiments, the host cells comprise constructs having all of the above characteristics wherein the host cell displays repressed or no uracil DNA glycosylase activity. This may be achieved by removal of the host cell ung gene. Use of host cells in the manufacture of pyrimidine deoxyribonucleotides e.g. thymidine is also disclosed.
Type:
Grant
Filed:
March 6, 2002
Date of Patent:
August 17, 2004
Assignee:
SmithKline Beecham Corporation
Inventors:
David Martin Anderson, Lin Liu, Sergey Podkovyrov, Baomin Wang
Abstract: The invention provides an antibody or a fragment thereof having specific binding affinity for superficial zone protein (SZP) or a variant, fragment, or protein core thereof, wherein the binding affinity of the antibody or fragment thereof for human superficial zone protein is the same or greater than the binding affinity for bovine superficial zone protein in a competitive binding assay, IAsys analysis, or BIAcore analysis. The present invention further provides hybidoma cells that produce the monoclonal antibody and antibody reagent kits comprising the antibody or fragment of the invention. Further provided by the invention are methods of SZP detection, methods of diagnosing a degenerative joint condition, and screening methods related to the use of the antibody or fragment thereof.
Type:
Grant
Filed:
February 9, 2001
Date of Patent:
April 13, 2004
Assignees:
SmithKline Beecham Corporation, Rush-Presbyterian St Luke's Medical Center
Inventors:
Jeff T. Hutchins, Klaus E. Kuettner, Kathryn Mason Lindley, Thomas M. Schmid, Barbara L. Schumacher, Stephen Anthony Stimpson, Jui-Lan Su
Abstract: S epidermidis polypeptides and DNA (RNA) encoding such polypeptides and a procedure for producing such polypeptides by recombinant techniques is disclosed. Also disclosed are methods for utilizing such polypeptides and DNA (RNA) for the treatment of infection, particularly infections arising from S epidermidis. Antagonists against the function of such polypeptides and their use as therapeutics to treat infection are also disclosed. Also disclosed are diagnostic assays for detecting diseases related to the presence of S epidermidis nucleic acid sequences and the polypeptides in a host. Also disclosed are diagnostic assays for detecting polynucleotides and polypeptides related to S epidermidis.
Abstract: The invention relates to the use of an Egr-1 transcription factor polypeptide or a biologically active fragment thereof, and to nucleic acid molecules encoding such polypeptides, in the manufacture of a medicament for the treatment of wounds in a mammal, including human. In addition, it relates to a sequence that is believed to include important regions involved in the transcription of the transcription factor Egr-1 in humans and in the regulation thereof. This sequence can be used to design appropriate nucleic acid molecules and vectors that can be used in the treatment of wounds, as well as in other treatment.
Type:
Grant
Filed:
January 29, 2001
Date of Patent:
February 10, 2004
Assignee:
SmithKline Beecham Corporation
Inventors:
Martin Braddock, Callum Jeffrey Campbell, Jean-Luc Schwachtgen
Abstract: The present invention provides a method of treating a subject with arthritis or an arthritic disease or preventing arthritis or arthritic disease in a subject, comprising administering to the subject a therapeutically effective amount of an agent that attenuates annexin function. Also provided are various methods of screening for agents and genes that increase collagen synthesis, decrease collagen degradation, or reduce or delay apoptosis, and methods of using the identified agents or nucleic acids for attaining or maintaining cartilage homeostasis, promoting cartilage repair, increasing collagen synthesis, decreasing collagen degradation, or reducing or delaying apoptosis. The invention also provides methods of decreasing mineralization of vesicles derived from chondrocytes and of promoting endochondral bone growth using agents that attenuates annexin function.
Type:
Grant
Filed:
December 21, 2000
Date of Patent:
November 18, 2003
Assignee:
SmithKline Beecham Corporation
Inventors:
Susan Chubinskaya, Jeff Hutchins, Juergen Mollenhauer, Francis X. Tavares, Stephen A. Thomson, Jennings F. Worley
Abstract: A method for performing chemical synthesis includes the steps of providing a solid support having cross links, a first set of cleavable links within the cross links, and a second set of cleavable links having sites on which to perform chemistry. A first chemical is coupled to the chemistry sites, and the first chemical is reacted with a second chemical to produce a reaction product. The links are cleaved to remove the cross links and to cleave the reaction product from the solid support.
Abstract: The present invention relates, in general, to nuclear receptors and, in particular, to the Constitutive Androstane Receptor (CAR; NR 1I3) and to a method of identifying ligands therefor.
Abstract: The present invention relates to the novel GABAB receptor subtypes GABAB-R1c and GABAB-R2 as well as to a novel, functional GABAB receptor which comprises a heterodimer of GABAB-R1 and GABAB-R2 receptor subunits. The present invention also relates to variants of the receptors, nucleotide sequences encoding the receptors and variants thereof and novel vectors, stable cell lines, antibodies, screening methods, methods of treatment and methods of receptor production.
Type:
Grant
Filed:
September 3, 1999
Date of Patent:
February 11, 2003
Assignee:
Smithkline Beecham Corporation
Inventors:
Ashley Antony Barnes, Alan Wise, Fiona Hamilton Marshall, Neil James Fraser, Julia Helen Margaret White, Steven Michael Foord