Abstract: This invention relates to a general methodology for efficient creation of trimeric soluble receptors for therapeutic applications. The process involves gene fusion between a soluble receptor with a ligand binding domain and a trimerization tag from the C-propeptide domain of pro-collagen, which is capable of self-assembly into a covalently linked trimer. Using both in vitro bioassays and an in vivo mouse model for collagen-induced arthritis (CIA), we show that the homotrimeric soluble TNF receptor produced with such method is a more potent blocker than dimeric TNF receptor decoys in inhibiting TNF-? mediated inflammatory diseases.
Abstract: Suitable dyes are used herein to indicate the presence of microbial contamination by spraying them onto surfaces in the form of an aqueous solution. The dye solution may also be allowed to dry, thus producing the dried residue of an aqueous solution. It's believed that these dyes change color in response to a change in polarity of the environment. Since water is a polar solvent and most bacteria are made from non-polar substances, the presence of bacteria changes the polarity of the environment, triggering a change visible by the unaided eye.
Type:
Grant
Filed:
December 16, 2004
Date of Patent:
March 30, 2010
Assignee:
Kimberly-Clark Worldwide, Inc.
Inventors:
Jason Lye, John Gavin MacDonald, Ning Wei, Stephanie Martin
Abstract: A chromogenic composition for detecting spilled blood includes a mixture of an acidified aqueous solution containing reduced FD&C Blue #1 and hydrogen peroxide. The chromogenic composition has a relatively long shelf life and will produce a bright blue visible color when contacting blood, thereby being useful for detecting spilled blood and blood trails from wounded game.
Abstract: The invention is a proteinaceous construct comprising a Factor VIII molecule having at least a portion of the B domain intact, which is conjugated to a water-soluble polymer such as polyethylene glycol having a molecular weight of greater than 10,000 Daltons. The construct has a biological activity of at least 80% of the biological activity of native Factor VIII, and the in vivo half-life of the construct is increased by at least 1.5 fold as compared to the in vivo half-life of native factor FVIII.
Type:
Grant
Filed:
March 29, 2007
Date of Patent:
March 23, 2010
Assignees:
Baxter International Inc., Baxter Healthcare
Inventors:
Juergen Siekmann, Katalin Varadi, Herbert Gritsch, Peter Turecek
Abstract: This invention relates to a highly efficient artificial low-density lipoprotein (LDL) carrier system for the targeted delivery therapeutic agents across the blood-brain barrier (BBB). In particular, this invention relates to artificial LDL particles comprised of three lipid elements: phosphatidyl choline, fatty-acyl-cholesterol esters, and at least one apolipoprotein. The present invention further relates to compositions, methods and kits comprising artificial LDL particles for targeting drugs to and across the BBB for the prevention and treatment of brain diseases.
Type:
Grant
Filed:
January 3, 2007
Date of Patent:
March 23, 2010
Assignee:
Blanchette Rockefeller Neurosciences Institute
Inventors:
Thomas Nelson, Alessandro Quattrone, Daniel Alkon
Abstract: Methods and compositions for producing secreted soluble receptors and biologically active polypeptides in trimeric forms are disclosed. The process involves fusing the DNA template encoding a soluble receptor with a ligand binding domain or biologically active polypeptide to a DNA sequence encoding a C-propeptide of collagen, which is capable of self-assembly into a covalently linked trimer. The resulting fusion proteins are secreted as trimeric soluble receptor analogs, which can be used for more efficient neutralization of the biological activities of their naturally occurring trimeric ligands.
Abstract: Compositions of the present invention, comprising at least one digestive enzyme (e.g., pancrelipase) are useful for treating or preventing disorders associated with digestive enzyme deficiencies. The compositions of the present invention can comprise a plurality of coated particles, each of which is comprised of a core coated with an enteric coating comprising at least one enteric polymer and 4-10% of at least one alkalinizing agent, or have moisture contents of about 3% or less, water activities of about 0.6 or less, or exhibit a loss of activity of no more than about 15% after six months of accelerated stability testing.
Type:
Grant
Filed:
October 9, 2009
Date of Patent:
February 9, 2010
Assignee:
Eurand Pharmaceuticals Ltd.
Inventors:
Giovanni Ortenzi, Marco Marconi, Luigi Mapelli
Abstract: The invention is a proteinaceous construct comprising a Factor VIII molecule which is conjugated to a water-soluble polymer via carbohydrate moieties of Factor VIII, and methods of preparing same.
Type:
Grant
Filed:
August 1, 2008
Date of Patent:
January 12, 2010
Assignees:
Baxter Healthcare S.A., Baxter International Inc.
Abstract: Pharmaceutical formulations of glutenase enzymes are provided. The enzymes find particular use in the treatment of a Celiac or dermatitis herpetiformis patient.
Type:
Grant
Filed:
February 23, 2005
Date of Patent:
December 8, 2009
Assignees:
The Board of Regents of the Leland Stanford Junior University, Alvine Pharmaceuticals, Inc.
Inventors:
Lu Shan, Michael Thomas Bethune, Chaitan Khosla, Jonathan David Gass
Abstract: The present invention relates to methods for enhancing the hemodynamic stability of an individual undergoing surgery by administering a composition comprising a hemoglobin-based oxygen carrier. In one embodiment, the present invention relates to the use of polyalkylene oxide modified hemoglobins with reduced cooperativity and a high oxygen affinity to enhance oxygen offloading as a preventative measure to avoid hemodynamic stability-related complications during surgery.
Abstract: Recombinant adenoviruses comprising modified fiber proteins which expand the tropism of the adenovirus in comparison to wild-type virus are disclosed. The modified fiber proteins described herein contain a peptide ligand for a cell surface binding site other than CAR comprising a 14 amino acid core sequence containing both fixed and variable amino acid residues. The invention includes isolated nucleic acid molecules encoding the modified adenovirus fiber proteins disclosed, as well as recombinant vectors and host cells containing said nucleic acid molecules. Methods of identifying peptide ligands that bind to cell binding sites other than CAR are included comprising screening a phage-display library of peptide ligands expressed within an adenovirus fiber knob context on CAR-negative cells.
Type:
Grant
Filed:
May 10, 2004
Date of Patent:
November 3, 2009
Assignee:
Instituto di Ricerche di Biologia Molecolare P. Angeletti S.p.A.
Abstract: This invention relates to the use of hypo-oncotic aqueous solutions of molecularly dispersed chemically modified high molecular weight crosslinked hemoglobins, namely so-called hemoglobin hyperpolymers, to prepare agents for the symptomatic, primarily life-saving treatment of acute pulmonary edema. Administration in particular is intravascular. Surprisingly, additive administration can be performed since according to the invention the colloidal-osmotic (=oncotic) pressure of the blood itself is essentially raised only slightly, and the blood volume is increased hardly at all. Administration pursuant to the invention is thus (almost) volume-neutral based on the blood into which the injection is made. A hyperpolymeric hemoglobin derivative is thus used therapeutically for the first time as a blood additive for the treatment of pulmonary edema.
Abstract: The invention provides protein subcellular localization assays using split fluorescent protein systems. The assays are conducted in living cells, do not require fixation and washing steps inherent in existing immunostaining and related techniques, and permit rapid, non-invasive, direct visualization of protein localization in living cells. The split fluorescent protein systems used in the practice of the invention generally comprise two or more self-complementing fragments of a fluorescent protein, such as GFP, wherein one or more of the fragments correspond to one or more beta-strand microdomains and are used to “tag” proteins of interest, and a complementary “assay” fragment of the fluorescent protein. Either or both of the fragments may be functionalized with a subcellular targeting sequence enabling it to be expressed in or directed to a particular subcellular compartment (i.e., the nucleus).
Abstract: The invention provides the use of an enzyme and a prodrug in the manufacture of a medicament for use in inducing an anti-tumor immune response in a human patient.
Type:
Grant
Filed:
September 29, 2006
Date of Patent:
June 2, 2009
Assignee:
Oxford Biomedica (UK) Limited
Inventors:
Richard Harrop, Miles Carroll, Susan Kingsman
Abstract: The present invention relates to identifying the risk of a subject developing renal stones utilizing an assessment of PTH agonist, antagonist and/or total PTH levels, optionally together with an assessment of serum and/or urine calcium levels and/or other analytes. The present description further relates to monitoring and guiding treatment for renal stones and kits useful therefore.
Abstract: Administering an effective dose of glutenase to a Celiac or dermatitis herpetiformis patient reduces levels of toxic gluten oligopeptides, thereby attenuating or eliminating the damaging effects of gluten.
Type:
Grant
Filed:
April 15, 2005
Date of Patent:
May 19, 2009
Assignee:
The Board of Trustees of the Leland Stanford Junior University
Inventors:
Justin L. Piper, Gary M. Gray, Chaitan Khosla
Abstract: The present invention is directed to methods for inducing desired activity in enzymes or microorganisms capable of producing the enzymes. The invention is further directed to methods of stabilizing activity in microorganisms. In specific embodiments, the invention provides methods for inducing and stabilizing nitrile hydratase activity, amidase activity, and asparaginase I activity. The invention further provides compositions comprising enzymes or microorganisms having induced and/or stabilized activity.
Type:
Grant
Filed:
January 30, 2007
Date of Patent:
May 12, 2009
Assignee:
Georgia State University Research Foundation, Inc.
Inventors:
George E. Pierce, Gene K. Drago, Sangeeta Ganguly
Abstract: The invention discloses a method of determining protease activity, in real time, using fluorescence polarization technology. In particular, the invention provides vectors and a method for their use, which expresses uncharacterized proteins conjugated to a fluorescence tag, which binds specifically to a fluorescent ligand. Cleavage of the recombinant protein results in a fragment of the expressed peptide and results in a change in fluorescence polarization of the fluorophore. The rate of change in fluorescence polarization can be measured in real time and is equivalent to the rate of protease cleavage.
Abstract: The present invention is directed to methods for inducing desired activity in enzymes or microorganisms capable of producing the enzymes. The invention is further directed to methods of stabilizing activity in microorganisms. In specific embodiments, the invention provides methods for inducing and stabilizing nitrile hydratase activity, amidase activity, and asparaginase I activity. The invention further provides compositions comprising enzymes or microorganisms having induced and/or stabilized activity.
Type:
Grant
Filed:
January 30, 2007
Date of Patent:
May 12, 2009
Assignee:
Georgia State University Research Foundation, Inc.
Inventors:
George E. Pierce, Gene Drago, Sangeeta Ganguly
Abstract: This invention provides labeled-substrate conjugates for assaying enzymes, particularly neuraminidases. Also provided are assays that are useful for identifying compounds that inhibit sialyltransferases or neuraminidases and may be useful in treating subjects with influenza. In particular, the present invention relates to methods of using such labeled substrate conjugates to screen for enzyme inhibitors, particularly in a high-throughput format.
Type:
Grant
Filed:
July 25, 2005
Date of Patent:
May 5, 2009
Assignee:
The Regents of the University of California