Patents Assigned to Arizona Board of Regents acting for and on behalf of Arizona State University
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Patent number: 5801222Abstract: Two new compounds which may be useful in the treatment of one or more neoplastic diseases through chemotherapy have been isolated from the Western Pacific Ocean marine sponge Phakellia sp. The cyclic octapeptides phakellistatin 10 and phakellistatin 11 are disclosed herein.As the included data demonstrate, phakellistatin 10 attained an LC.sub.50 of less than 10.sup.-5 M per milliliter against the MDA-MB-435 breast cancer cell line. It also achieved total growth inhibition for two breast cancers and two CNS cancer cell lines at a concentration of less than 10.sup.-6 M per milliliter. The included data for phakellistatin 11 shows a moderately higher level of in vitro activity as shown by an LC.sub.50 of less than 10.sup.-5 M per milliliter against the MDA-MB-435 breast cancer cell line and five other cell lines. It also achieved total growth inhibition for two breast cancers, one CNS cancer, one Ovarian cancer, and one non-small cell lung cancer cell lines at a concentration of less than 10.sup.Type: GrantFiled: December 20, 1994Date of Patent: September 1, 1998Assignee: Arizona Board of Regents acting on behalf of Arizona State UniversityInventors: George R. Pettit, Rui Tan
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Patent number: 5665860Abstract: This application discloses seven newly synthesized pentapeptide amides and our tetrapeptide amides. The synthesis utilized both naturally occurring and modified amino acids; the modified amino acids are constituents of the well known dolastatin 10 and dolastatin 15 which are structurally distinct peptides with excellent antineoplastic activity. These peptides were constructed by introducing a peptide bond between selected amino acids and modified amino acids and coupling the resulting di- and tri-peptides to obtain peptides having a high anticancer activity against a series of human cancer cell lines.Type: GrantFiled: June 13, 1996Date of Patent: September 9, 1997Assignee: Arizona Board of Regents acting on behalf of Arizona State UniversityInventors: George R. Pettit, Jayaram K. Srirangam, Michael D. Williams
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Patent number: 5663149Abstract: The synthesis and elucidation of nineteen heterocyclic or halophenyl amide erivatives of dolastatin 10 are disclosed. These compounds and the methods of producing those compounds offer demonstrated significant in vitro activity against several human cancer cell lines. These compounds and the methods of producing those compounds offer a commercially viable alternative to natural and synthetic dolastatin 10.Type: GrantFiled: December 13, 1994Date of Patent: September 2, 1997Assignee: Arizona Board of Regents acting on behalf of Arizona State UniversityInventors: George R. Pettit, Jayaram K. Srirangam, Darko Kantoci
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Patent number: 5646246Abstract: The cytostatic, cyclic peptides; phakellistatin 4, phakellistatin 5, phakellistatin 6, phakellistatin 7, phakellistatin 8 and phakellistatin 9 were isolated from the Western Pacific Ocean sponge Phakellia costata. Structural determination was accomplished by utilizing high-field, 2D-NMR experiments and confirmed by results of FAB-MS/MS studies. The absolute configurations were deduced by analyzing the acid hydrolysates using chiral gas chromatographic analytical techniques. The new cyclic peptides were found to have significant in vitro P388 ED.sub.50 values which range between 0.18 .mu.g/ml and 4.1 .mu.g/ml.Type: GrantFiled: November 14, 1994Date of Patent: July 8, 1997Assignee: Arizona Board of Regents acting on behalf of Arizona State UniversityInventors: George R. Pettit, Junping Xu
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Patent number: 5639881Abstract: Pyrimido[4,5-g]quinazoline quinone derivatives were synthesized as anthranone-like reductive alkylating agents. Like many naturally-occurring antibiotics, these quinone derivatives are designed to afford an alkylating quinone methide species upon reduction and leaving group elimination. Kinetic studies of pyrimido[4,5-g]quinazoline hydroquinones provided evidence of quinone methide intermediates able to trap nucleophiles (alkylation) and protons. The rate of quinone methide formation is determined by the hydroquinone free energy. Thus, a linear free energy relationship for quinone methide formation was obtained by plotting rates of quinone methide formation, as the log, versus the quinone reduction potential. The pyrimido[4-5-g]quinazoline quinone methides fall on this free energy plot, showing that these species are formed by the same mechanism as the other structurally-diverse quinone methides previously studied in this research group.Type: GrantFiled: November 8, 1991Date of Patent: June 17, 1997Assignee: Arizona Board of Regents acting on behalf of Arizona State UniversityInventors: Edward B. Skibo, Robert H. Lemus
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Patent number: 5635483Abstract: New tetrapeptides bearing modified phenethyl amides are elucidated and syesized and found to exhibit tumor inhibiting effects when measured against the NCI screen for six major types of human cancer and against the murine P388 lymphocytic cell line. The new modified tetrapeptides phenethyl amides are 6(a-k).Type: GrantFiled: December 3, 1992Date of Patent: June 3, 1997Assignee: Arizona Board of Regents acting on behalf of Arizona State UniversityInventors: George R. Pettit, Jozsef Barkoczy
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Patent number: 5602330Abstract: The present invention comprises a highly sensitive non-contact force microscope having a coaxial cantilever-tip configuration and a method of forming such configuration. The non-contact microscope obtains high resolution graphical images of a sample surface topography, and/or other properties thereof including its electrostatic, magnetic, or Van der Waals forces.Type: GrantFiled: May 25, 1995Date of Patent: February 11, 1997Assignee: Arizona Board of Regents acting on behalf of Arizona State UniversityInventors: Ralph V. Chamberlin, Anthony DiCarlo
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Patent number: 5599902Abstract: The sea hare Dolabella auricularia has yielded many structurally distinct ptides which possess antineoplastic activity. Presently the compound denominated "dolastatin 10" represents the most important of such peptides because of its demonstrated potential as an anticancer drug.The present invention relates to the systematic creation of seven unique pentapeptides by selectively coupling a tripeptide-trifluoroacetate salt with a preselected dipeptide trifluoroacetate salt which provide active molecules capable of emulating the measured therapeutic effect of dolastatin 10.Type: GrantFiled: November 10, 1994Date of Patent: February 4, 1997Assignee: Arizona Board of Regents acting on behalf of Arizona State UniversityInventors: George R. Pettit, Jayaram K. Srirangam
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Patent number: 5583224Abstract: Substantially pure compositions of matter selected from the group of cephalostatin 7, cephalostatin 8, and cephalostatin 9 having anti-neoplastic activity are disclosed.Type: GrantFiled: January 19, 1993Date of Patent: December 10, 1996Assignee: Arizona Board of Regents acting on behalf of Arizona State UniversityInventors: George R. Pettit, Yoshiaki Kamano
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Patent number: 5569786Abstract: New antineoplastic substances have been isolated, structurally elucidated and synthesized having a general structural formula of: ##STR1## wherein: R.sub.1 is OH or OCH.sub.3 ;R.sub.2 is H or OCH.sub.3 ; or R.sub.1 R.sub.2 is --OCH.sub.2 O--;R.sub.3 is H or OH; andR.sub.4 is OH or OCH.sub.3.These substances have been denominated "combretastatin A-1, -A-2, -A-3, -B-1, -B-2, -B-3 and -B-4". preparation containing the substances and methods of treating a host inflicted with a neoplastic growth with the preparation is described.Type: GrantFiled: November 15, 1994Date of Patent: October 29, 1996Assignee: Arizona Board of Regents acting on behalf of Arizona State UniversityInventors: George R. Pettit, Sheo B. Singh
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Patent number: 5561122Abstract: Disclosed herein are Combretastatin A-4 Prodrugs, having the general strure set forth below, which are useful in the treatment of one or more neoplastic diseases by means of chemotherapy.Type: GrantFiled: December 22, 1994Date of Patent: October 1, 1996Assignee: Arizona Board of Regents acting on behalf of Arizona State UniversityInventor: George R. Pettit
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Patent number: 5554725Abstract: The present invention relates to the synthesis of natural (-)- dolastatin and the elucidation of the absolute configuration of this important sea hare constituent. A segment synthetic strategy was utilized for obtaining the Dolabella auricularia (Indian Ocean sea hare) depsipeptide dolastatin 15. Reaction of protected (S)-Hiva-(S)-Phe (2c) with isopropenyl chloroformate followed by Meldrum's ester, cyclization (2c.fwdarw.3a) of the product in toluene and finally methylation afforded the key (S)-dolapyrrolidine (Dpy) derivative (3b). Condensation of tripeptide (8) with the three unit Dpy segment (5b) followed by deprotection and coupling (diethyl phosphorocyanidate) led to dolastatin 15 in 11% overall yield. The powerful and selective activity of dolastatin 15 against the U.S. National Cancer Institute's panel of human cell lines is reported.Type: GrantFiled: September 14, 1994Date of Patent: September 10, 1996Assignee: Arizona Board of Regents acting on behalf of Arizona State UniversityInventor: George R. Pettit
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Patent number: 5530097Abstract: This application discloses seven newly synthesized pentapeptide amides and our tetrapeptide amides. The synthesis utilized both naturally occurring and modified amino acids; the modified amino acids are constituents of the well known dolastatin 10 and dolastatin 15 which are structurally distinct peptides with excellent antineoplastic activity. These peptides were constructed by introducing a peptide bond between selected amino acids and modified amino acids and coupling the resulting di- and tri-peptides to obtain peptides having a high anticancer activity against a series of human cancer cell lines.Type: GrantFiled: August 1, 1994Date of Patent: June 25, 1996Assignee: Arizona Board of Regents acting on behalf of Arizona State UniversityInventors: George R. Pettit, Jayaram K. Srirangam, Michael D. Williams
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Patent number: 5529989Abstract: Pancratistatin has been selected for pre-clinical development but is sparingly soluble in water. A disodium phosphate derivative has been synthesized which is water soluble and is bioequivalent thereof. The critical step in the synthesis of the phenolic phosphate was phosphorylation of 1,2,3,4-tetraacetoxy-pancratistatin with dibenzyloxy(N,N-diisopropylamido)phosphine.Type: GrantFiled: January 9, 1995Date of Patent: June 25, 1996Assignee: Arizona Board of Regents acting on behalf of Arizona State UniversityInventors: George R. Pettit, Sally Freeman
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Patent number: 5521284Abstract: The isolation, elucidation and synthetic replication of novel pentapeptide mides and esters are described. The compounds have the general structure ##STR1## in which R.sub.1 and R.sub.2 are selected as shown below: ##STR2##R.sub.1 =CH.sub.3 ; R.sub.2 =--O--CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.3 16a)R.sub.1 =CH.sub.3 ; R.sub.2 =--O--CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.3 16b)R.sub.1 =CH.sub.3 ; R.sub.2 =--NH--CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.Type: GrantFiled: August 1, 1994Date of Patent: May 28, 1996Assignee: Arizona Board of Regents acting on behalf of Arizona State UniversityInventors: George R. Pettit, Jayaram K. Srirangam
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Patent number: 5519050Abstract: The Micronesian marine sponge Phakellia sp. has been found to contain cern key members of the antineoplastic halichondrin/halistatin family. These compounds include halichondrin B, homohalichondrin B, halistatin 1, and halistatin 3.Halistatin 3 is a newly discovered member of this family. It inhibited both the P388 leukemia cell line and selected brain, lung, colon, ovarian, renal, and melanoma type cancer cell lines with ED.sub.50 /GI.sub.50 concentrations on the order of 3.times.10.sup.-5 .mu.g/ml.Type: GrantFiled: April 7, 1995Date of Patent: May 21, 1996Assignee: Arizona Board of Regents acting on behalf of Arizona State UniversityInventors: George R. Pettit, Yoshitatsu Ichihara
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Patent number: 5518970Abstract: The present invention relates generally to a novel and unique class of gly materials and methods of making such materials in which substantially all of the anions are nitride ions, in contrast to the oxide ions of conventional optical glasses, or the fluoride ions of the more recently discovered fluoride optical glasses. The chemical nature of these new glasses dispose the glassy materials to a remarkable combination of desirable properties, including, but not limited to, high hardness, high refractive index and high softening temperature.Type: GrantFiled: May 24, 1995Date of Patent: May 21, 1996Assignee: Arizona Board of Regents acting on behalf of Arizona State UniversityInventors: Paul F. McMillan, C. Austen Angell, Tor Grande, John R. Holloway
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Patent number: 5504191Abstract: Herein disclosed are several pentapeptide methyl ester derivatives of dolatin 10, using both naturally occurring and modified amino acids. The selected modified amino acids are constituents of dolastatin 10 which is a structurally distinct peptide with excellent in vitro and in vivo antineoplastic activity.Type: GrantFiled: August 1, 1994Date of Patent: April 2, 1996Assignee: Arizona Board of Regents acting on behalf of Arizona State UniversityInventors: George R. Pettit, Jayaram K. Srirangam, Michael D. Williams
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Patent number: 5455211Abstract: The present invention relates generally to a novel and unique class of gly materials and methods of making such materials in which substantially all of the anions are nitride ions, in contrast to the oxide ions of conventional optical glasses, or the fluoride ions of the more recently discovered fluoride optical glasses. The chemical nature of these new glasses dispose the glassy materials to a remarkable combination of desirable properties, including, but not limited to, high hardness, high refractive index and high softening temperature.Type: GrantFiled: April 19, 1994Date of Patent: October 3, 1995Assignee: Arizona Board of Regents acting on behalf of Arizona State UniversityInventors: Paul F. McMillan, C. Austen Angell, Tor Grande, John R. Holloway
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Patent number: 5430053Abstract: A new-type of macrocyclic lactone denominated "dictyostatin 1" bearing a membered ring system is isolated from a Republic of Maldives marine sponge in the genus Spongia sp. and found to strongly inhibit the growth of an important selection of U.S. National Cancer Institute human cancer cell system and the murine P388 lymphocytic leukemia (PS ED.sub.50 3.8.times.10.sup.-4 mg/ml).Type: GrantFiled: April 19, 1994Date of Patent: July 4, 1995Assignee: Arizona Board of Regents acting on behalf of Arizona State UniversityInventors: George R. Pettit, Zbigniew A. Cichacz