Patents by Inventor George R. Pettit

George R. Pettit has filed for patents to protect the following inventions. This listing includes patent applications that are pending as well as patents that have already been granted by the United States Patent and Trademark Office (USPTO).

  • Patent number: 5504191
    Abstract: 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: Grant
    Filed: August 1, 1994
    Date of Patent: April 2, 1996
    Assignee: Arizona Board of Regents acting on behalf of Arizona State University
    Inventors: George R. Pettit, Jayaram K. Srirangam, Michael D. Williams
  • Patent number: 5494893
    Abstract: The cytostatic cycloheptapeptide stylostatin 2 was isolated respectively, from the South and Western Pacific Ocean sponges Stylotella sp. and Phakellia costata. Structural determination was accomplished by utilizing high-field (500 MHz) 2D-NMR experiments and confirmed by an X-ray crystal structure determination to provide the assignment cyclo(Pro-Leu-Ile-Phe-Ser-Pro-Ile). The absolute configuration was established by chiral gas chromatographic analytical technique. The cyclic heptapeptide backbone was found to include a .beta.-turn, type VIa, incorporating a cis peptide bond, at -Ser-Pro.
    Type: Grant
    Filed: November 14, 1994
    Date of Patent: February 27, 1996
    Assignee: Arizona Board of Regents, a body corporate acting on behalf of Arizona State University
    Inventors: George R. Pettit, Jayaram K. Srirangam
  • Patent number: 5436400
    Abstract: An Eastern Indian Ocean marine sponge in the genus Spongia was located in the Republic of the Maldives and found to contain a structurally unprecedented macrocyclic lactone named spongistatin 1. The new perhydropyran-containing structure, as shown below, was found to be remarkably potent and specific, log molar TCI.sub.50 to <-10, against twenty human cancer cell lines in the U.S. National Cancer Institute's panel of sixty.
    Type: Grant
    Filed: January 19, 1993
    Date of Patent: July 25, 1995
    Assignee: Arizona Board of Regents
    Inventors: George R. Pettit, Zbigniew A. Cichacz, Cherry L. Herald
  • Patent number: 5430053
    Abstract: 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: Grant
    Filed: April 19, 1994
    Date of Patent: July 4, 1995
    Assignee: Arizona Board of Regents acting on behalf of Arizona State University
    Inventors: George R. Pettit, Zbigniew A. Cichacz
  • Patent number: 5426194
    Abstract: An intensive long-term investigation of marine organisms as sources of new anticancer drugs has led to the isolation and structural elucidation (primarily by high field NMR and mass spectrometry) of halistatin 1, a new polyether macrolide of the halipyran-type, from the Western Indian Ocean sponge Phakellia carteri. Halistatin 1 (8.8.times.10.sup.-7 % yield) caused the accumulation of cells arrested in mitosis, inhibited tubulin polymerization, and inhibited the binding of radiolabeled vinblastine and GTP to tubulin.
    Type: Grant
    Filed: January 19, 1993
    Date of Patent: June 20, 1995
    Assignee: Arizona Board of Regents, a body corporate acting on behalf of Arizona State University
    Inventors: George R. Pettit, Rui Tan, Feng Gao
  • Patent number: 5410024
    Abstract: The synthesis of useful peptides presents a promising approach to new theeutic agents. The Dolastatins, a series of linear and cyclic antineoplastic and/or cytostatic peptides isolated from Indian Ocean sea hare Dolabella auricularia represent excellent leads for synthetic modification.The extraordinary inhibition of cell growth shown by the pentapeptideamides against six major types of human cancer has been presented. The intermediates of these reaction also show anticancer activity against the murine P388 lymphocytic leukemia cell line.
    Type: Grant
    Filed: January 21, 1993
    Date of Patent: April 25, 1995
    Assignee: Arizona Board of Regents acting on behalf of Arizona State University
    Inventors: George R. Pettit, Jozsef Barkoczy, Darko Kantoci
  • Patent number: 5409953
    Abstract: 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;R.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". Pharmaceutical preparation containing the substances and methods of treating a host inflicted with a neoplastic growth with the preparation is described.
    Type: Grant
    Filed: February 10, 1992
    Date of Patent: April 25, 1995
    Assignee: Arizona Board of Regents acting on behalf of Arizona State University
    Inventors: George R. Pettit, Sheo B. Singh
  • Patent number: 5393897
    Abstract: A Southwest Indian Ocean marine sponge Spirastrella spinispirulifera (bri colored reds and purples) has been found to contain new and exceptionally active cell (human cancer) growth inhibitors spongistatin 5, spongistatin 7, spongistatin 8 and spongistatin 9. These compositions are related to spongistatin 1, which was found in a black Spongia sp. in the Porifera family. A method of treating human cancer cells with spongistatin 5 and spongistatin 7 is also disclosed.
    Type: Grant
    Filed: July 2, 1993
    Date of Patent: February 28, 1995
    Assignee: Arizona Board of Regents acting on behalf of Arizona State University
    Inventors: George R. Pettit, Zbigniew A. Cichacz, Cherry L. Herald
  • Patent number: 5352804
    Abstract: An intensive long-term investigation of marine organisms as sources of new anticancer drugs has led to the isolation and structural elucidation (primarily by high field NMR and mass spectrometry) of halistatin 2, a new polyether macrolide of the halipyran-type, from the Western Indian Ocean sponge Axinella cf. carteri (Dendy). Halistatin 2 (1.4.times.10.sup.-6 % yield) caused the accumulation of cells arrested in mitosis, inhibited tubulin polymerization, and inhibited the binding of radiolabeled vinblastine and GTP to tubulino. Further, Halistatin 2 displayed significant activity against selected human tumor cell lines.
    Type: Grant
    Filed: January 19, 1993
    Date of Patent: October 4, 1994
    Assignee: Arizona Board of Regents, a body corporate, acting on behalf of Arizona State University
    Inventors: George R. Pettit, Feng Gao
  • Patent number: 5328929
    Abstract: A black Spongia sp. in the Porifera class Demospongiae has been found to contain two new and exceptionally active cell (human cancer) growth inhibitors named spongistatin 2 and spongistatin 3. A bright colored Southwest Indian Ocean sponge Spirastrella spinispirulifera has also been found to contain related human cancer cell growth inhibitors named spongistatin 4 and spongistatin 6. A method of treating human cancer cells with spongistatin 1, spongistatin 2, spongistatin 3, spongistatin 4 and spongistatin 6 is also disclosed. The approximate mean GI.sub.50 of the disclosed compounds in the NCI cell line panel is about 10.sup.-10 .mu.g/ml.
    Type: Grant
    Filed: July 2, 1993
    Date of Patent: July 12, 1994
    Assignee: Arizona Board of Regents
    Inventors: George R. Pettit, Zbigniew A. Cichacz, Cherry L. Herald
  • Patent number: 5196447
    Abstract: The marine bryozoan Bugula neritina has been found to contain a novel 22-membered macrocyclic lactone which is an inhibitor of lymphocytic leukemia as measured by the US National Cancer Institute's P 388 and in vitro evaluation system. The novel lactone is herein denominated "neristatin 1" and is elucidated.
    Type: Grant
    Filed: August 8, 1991
    Date of Patent: March 23, 1993
    Assignee: Arizona Board of Regents, a body Corporate of The State of Arizona, Acting on behalf of Arizona State University
    Inventors: George R. Pettit, Feng Gao
  • Patent number: 5138036
    Abstract: A new cytostatic depsipeptide, designated "dolastatin 14", was isolated from the Indian Ocean shell-less mollusk Dolabella auricularia. Dolastatin 14 inhibited growth of the PS leukemia with ED.sub.50 0.0018 .mu.g/mL. Pharmaceutical preparations and therapeutic regimens utilizing Dolastatin 14, its synthetic counterpart and pharmaceutically active derivatives are disclosed.
    Type: Grant
    Filed: November 13, 1989
    Date of Patent: August 11, 1992
    Assignee: Arizona Board of Regents acting on behalf of Arizona State University
    Inventors: George R. Pettit, Yoshiaki Kamano, Cherry L. Herald
  • Patent number: 5130414
    Abstract: A new and demonstratably active cyclo-octapeptide is isolated from the South Pacific Ocean Hymeniacidon sp. and structurally elucidated. The substance, herein denominated Hymenistatin 1, demonstrated utility by inhibiting tumor growth when measured by the National Cancer Institute P388 leukemia cell line (ED.sub.50 =3.5 .mu.g/mL).
    Type: Grant
    Filed: November 30, 1989
    Date of Patent: July 14, 1992
    Assignee: Arizona Board of Regents, a body corporate of Arizona State University
    Inventor: George R. Pettit
  • Patent number: 5076973
    Abstract: Synthesis of dolastatin 3 is accomplished by one amino acid unit addition from L-Pro-OMe employing diethyl phosphorocyanidate-triethylamine for peptide bond formation and N-Boc protection (trifluoroacetic acid cleavage). Thereafter Boc-L-Leu-L-(gln)Thz-(gly)Thz-L-Val-L-Pro-OMe was obtained, successively crystallized from ethanol-diethyl ether, converted to the OPfp active ester, Boc cleavage and cyclization in dioxane containing t-butanol and 4-pyrrolidinopyridine to yield synthetic (-)-dolastatin 3.
    Type: Grant
    Filed: October 24, 1988
    Date of Patent: December 31, 1991
    Assignee: Arizona Board of Regents
    Inventors: George R. Pettit, Cedric W. Holzapfel
  • Patent number: 5072004
    Abstract: Bryostatin 2 is converted to bryostatin 1 by a selective protection and dotection strategy involving the C-26 hydroxyl group.
    Type: Grant
    Filed: December 31, 1990
    Date of Patent: December 10, 1991
    Assignee: Arizona Board of Regents acting on behalf of Arizona State University
    Inventor: George R. Pettit
  • Patent number: 5047532
    Abstract: The Indian Ocean (South African) marine worm Cephalodiscus gilchristi (Hemichordata Phylum) has been found to contain a series of unusual disteroidal alkaloids designated the Cephalostatins which demonstrate exceptionally potent lymphocytic leukemia (murine P388) cell line inhibitory activity (to ED.sub.50 10.sup.-9 .mu.g/ml). Two new disteriodal alkaloids bearing aromatic C-rings having ED.sub.50 of 10.sup.-2 and 10.sup.-3 .mu.g/mL were isolated and assigned structures based on rigorous interpretation of two-dimensional 400 MHz.sup.1 H and .sup.13 C-nmr. These substances were denominated Cephalostatin 5 and Cephalostatin 6, respectively.
    Type: Grant
    Filed: July 28, 1989
    Date of Patent: September 10, 1991
    Assignee: Arizona Board of Regents, acting on behalf of Arizona State University
    Inventors: George R. Pettit, Yoshiaki Kamano
  • Patent number: 4997817
    Abstract: An unusal cytostatic (PS ED.sub.50 4 ug/ml) lignan ester has been isolated from the Central American tree Phyllanthus acuminatus and is herein designated Phyllanthostatin A. Separation of a methanol extract of the root by size exclusion chromatography, high speed countercurrent distribution and semi-preparative hplc afforded glycoside in 0.007% yield. In solution, phyllanthostatin A was slowly transformed into justicidin-B.
    Type: Grant
    Filed: January 19, 1990
    Date of Patent: March 5, 1991
    Assignee: Arizona Board of Reagents
    Inventor: George R. Pettit
  • Patent number: 4996237
    Abstract: The African tree Combretum caffrum (Combretaceae) has been found to contain an agent which is a powerful inhibitor of tubulin polymerization (IC50 2-3 .mu.M), the growth of murine lymphocytic leukemia (L1210 and P388 with ED50 <0.003 mg/ml and human colon cancer cell lines (e.g. VoLo with ED50 <0.01 .mu.g/ml). This agent is herein denominated "combretastatin A-4". The structure assigned by spectral techniques was confirmed by synthesis.
    Type: Grant
    Filed: February 22, 1988
    Date of Patent: February 26, 1991
    Assignee: Arizona Board of Regents
    Inventors: George R. Pettit, Sheo B. Singh
  • Patent number: 4986988
    Abstract: The Indian Ocean sea hare Dolabella auricularia has been found to contain a new cell growth inhibitory and antineoplastic (P388 leukemia) cyclodepsipeptide designated dolastatin 13.sup.(1) and a companion substance dehydrodolastatin 13.sup.(2). A series of high field (400 MHz) 2D-NMR experiments including sequential analyses by HMBC and NOE techniques and tandem mass spectrometry provided structural determinations. Dolastatin 13 and dehydrodolastatin 13 represent a new class of cyclodepsipeptides. Pharmaceutical preparations and therapeutic regimens employing these new cytostatic depsipeptides are disclosed.
    Type: Grant
    Filed: May 18, 1989
    Date of Patent: January 22, 1991
    Assignee: Arizona Board of Regents
    Inventors: George R. Pettit, Yoshiaki Kamano
  • Patent number: 4985436
    Abstract: A new antineoplastic substance denominated "pancratistatin". Methods of isolating natural and synthetic pancratistatin and 7-deoxynarciclasine and the pharmaceutically acceptable derivatives thereof to make a pharmaceutical preparation therefrom and methods for treating a host afflicted with a neoplasm with said preparations.
    Type: Grant
    Filed: February 17, 1984
    Date of Patent: January 15, 1991
    Assignee: Arizona Board of Regents
    Inventor: George R. Pettit