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| 20080206231 | Compositions and Methods for Treating Disease - The present invention discloses for the first time that the insulin receptor (IR) is a target of Herstatin, which modulates IR and IR-mediated intracellular signaling. In preferred aspects, Herstatin binds at nM concentrations to cell-surface IR, up-regulates basal IR expression by several-fold, induces the accumulation of pro-IR, and stimulates insulin activation of the ERK pathway. Moreover, these changes in insulin signaling are accompanied by alterations in IGF-IR expression, IRS-2 levels, and the serine phosphorylation state of both IRS-1 and IRS-2. Preferred aspects provide novel therapeutic methods and pharmaceutical compositions for treatment of conditions associated with altered IR expression or IR-mediated signaling, including but not limited to insulin resistance syndrome, pre-diabetic conditions, metabolic syndrome, type 1 and type 2 diabetes, cardiac disease, diabetes-associated vascular disease, atherosclerosis, hypertension, diabetes-associated lipid metabolism disorders (dyslipidemia), obesity, critical illness, neurodegenerative disorders, and combinations thereof, and cancer. | 08-28-2008 |
| 20090270316 | HER-2 BINDING ANTAGONISTS - There is disclosed a pharmaceutical composition for treating solid tumors that overexpress HER-2, comprising an agent selected from the group consisting of (a) an isolated polypeptide having from about 50 to 79 amino acids taken from the sequence of SEQ ID NO:1, wherein the polypeptide binds to the extracellular domain ECD of HER-2 at an affinity of at least 108, (b) an isolated and glycosylated polypeptide having from about 300 to 419 amino acids taken from the sequence of SEQ ID NO:2, wherein the C terminal 79 amino acids are present, and wherein at least three N-linked glycosylation sites are present, (c) a monoclonal antibody that binds to the ECD of HER-2, and (d) combinations thereof, with the proviso that the agent cannot be the monoclonal antibody alone, and pharmaceutically acceptable carrier. | 10-29-2009 |
| 20100119521 | COMPOSITIONS AND METHODS FOR TREATING CANCER BY MODULATING HER-2 AND EGF RECEPTORS - An alternative HER-2/neu product, herstatin, consists of subdomains I and II from the ectodomain of p185HER-2 and a unique 79 amino acid C-terminus encoded by intron 8. Recombinant herstatin added to cells was found to bind to and inhibit p185HER-2. The effects of ectopic expression of herstatin in combination with either p185HER-2 or with its homolog, the EGF receptor, in several cell lines was studied. Cotransfection of herstatin with HER-2 inhibited p185HER-2 levels and caused an approximate 8-fold reduction in p185 tyrosine phosphorylation. Inhibition of p185HER-2 tyrosine phosphorylation corresponded to a dramatic decline in colony formation by cells that coexpressed p185HER-2 and herstatin. Herstatin also interferred with EGF activation of the EGF receptor in cotransfected cells as demonstrated by impaired receptor tyrosine phosphorylation, reduced receptor down-regulation, and growth suppression. For both p185HER-2 and the EGF receptor, the extent of inhibition was affected by the expression levels of herstatin relative to the receptor. Herstatin is an autoinhibitor of p185HER-2 and expands its inhibitory activity to another member of the group I family of receptor tyrosine kinases, the EGF receptor. Herstatin blocked the activated Akt-mediated EGF survival signal, as well as transforming growth factor alpha (TGFα)-mediated EGF receptor activation, survival signal and proliferation signal. Purified recombinant herstatin specifically inhibited human carcinoma cells that over-express HER-2, and was effectively absorbed into the blood of intraperitoneally injected mice, where it was not proteolytically degraded and was present for between one and three hours. | 05-13-2010 |
| 20100267027 | HER-2 BINDING ANTAGONISTS - There is disclosed a a pharmaceutical composition for treating solid tumors that overexpress HER-2, comprising an agent selected from the group consisting of (a) an isolated polypeptide having from about 50 to 79 amino acids taken from the sequence of SEQ ID NO:1, wherein the polypeptide binds to the extracellular domain ECD of HER-2 with an affinity binding constant of at least 10 | 10-21-2010 |
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| 20090147603 | MEMORY WITH LOW POWER MODE FOR WRITE - The present invention describes circuitry and a method of providing a low power WRITE mode of operation for an integrated circuit comprising an SRAM memory to provide a reduced IDDQ relative to the IDDQ of a full active mode. In one aspect, the circuitry includes an SRAM memory array, mode control circuitry coupled to the array and configured to alter a supply voltage level to the SRAM array based on a mode of operation. The circuitry also includes control inputs coupled to the mode control circuitry for selecting one of the low power write mode, the full active mode, and optionally a retention mode of operation. The mode control circuitry is configured to receive the control inputs to select one of the three modes of operation, and to alter one or more supply voltage levels to the array, for example, the Vss supply voltage using a Vss supply circuit and the Vdd supply voltage using a Vdd supply circuit, based on the selected mode of operation. The mode control circuitry may also comprise a bitline precharge circuit configured to alter a bitline precharge voltage. | 06-11-2009 |
| 20090316500 | Memory Cell Employing Reduced Voltage - A memory array is provided having a memory cell coupled to a read word line and a write word line of the memory array and peripheral circuits for reading and writing to the memory cell. The memory cell comprises a storage element for storing a logical state of the memory cell powered at a reduced voltage during at least one functional operation and a write access circuit configured to connect the storage element to at least a first write bit line in the memory array in response to a write signal on the write word line for writing the logical state to the memory cell. The memory cell further comprises a read access circuit including an input node connected to the storage element and an output node connected to a read bit line of the memory array. The read access circuit is enabled and configured to read the logic state of the storage element in response to a read signal on the read word line. The reduced voltage is a voltage that is reduced relative to a peripheral operating voltage of at least one peripheral circuit associated with reading and/or writing of the memory cell. | 12-24-2009 |
| 20110069565 | MEMORY CELL EMPLOYING REDUCED VOLTAGE - A memory array is provided having a memory cell coupled to a read word line and a write word line of the memory array and peripheral circuits for reading and writing to the memory cell. The memory cell comprises a storage element for storing a logical state of the memory cell powered at a reduced voltage during at least one functional operation and a write access circuit configured to connect the storage element to at least a first write bit line in the memory array in response to a write signal on the write word line for writing the logical state to the memory cell. The memory cell further comprises a read access circuit including an input node connected to the storage element and an output node connected to a read bit line of the memory array. The read access circuit is enabled and configured to read the logic state of the storage element in response to a read signal on the read word line. The reduced voltage is a voltage that is reduced relative to a peripheral operating voltage of at least one peripheral circuit associated with reading and/or writing of the memory cell. | 03-24-2011 |
