| Non-cytotoxic pap mutants -> Monitor Keywords |
|
|
 
Non-cytotoxic pap mutantsNon-cytotoxic pap mutants description/claimsThe Patent Description & Claims data below is from USPTO Patent Application 20090156497, Non-cytotoxic pap mutants. Brief Patent Description - Full Patent Description - Patent Application Claims
This application is a divisional of U.S. application Ser. No. 10/467,009, filed Jul. 12, 2004, which is a national phase entry under 35 U.S.C. § 371 of International Application No. PCT/US02/02792, filed Feb. 1, 2002, which claims the benefit of the filing date of U.S. Provisional Application No. 60/266,396, filed Feb. 2, 2001, the disclosures of which are hereby incorporated herein by reference. The invention was supported by NSF grant MCB99-82498. Thus, the Government may have rights in the invention. The invention relates to pokeweed antiviral protein and expression of nucleic acids encoding various PAP mutants in transgenic plants. Many commercially valuable agricultural crops are prone to infection by plant viruses. These viruses are capable of inflicting significant damage to a crop in a given season, and thus can drastically reduce its economic value. The reduction in economic value to the farmer in turn results in a higher cost of goods to ultimate purchasers. Several published studies have been directed to the expression of plant virus capsid proteins in a plant in an effort to confer resistance to viruses. See, e.g., Abel et al., Science 232:738-743 (1986); Cuozzo et al., Bio/Technology 6:549-557 (1988); Hemenway et al., EMBO J. 7:1273-1280 (1988); Stark et al., Bio/Technology 7:1257-1262 (1989); and Lawson et al., Bio/Technology 8:127-134 (1990). The transgenic plants exhibited resistance only to the homologous virus and related viruses, however, and not to unrelated viruses. Kawchuk et al., Mol. Plant-Microbe Interactions 3(5):301-307 (1990), disclose the expression of wild-type potato leafroll virus (PLRV) coat protein gene in potato plants. Although the infected plants exhibited resistance to PLRV, all of the transgenic plants that were inoculated with PLRV became infected with the virus and thus allowed for the continued transmission of the virus such that high levels of resistance could not be expected. See U.S. Pat. No. 5,304,730. Pokeweed antiviral protein (PAP) is a 29-kDa Type I ribosome-inhibiting protein (RIP) found in the cell walls of Phytolacca americana (pokeweed). See, Wang et al., Adv. Virus Res. 55:325-356 (2000). It is a single polypeptide chain that catalytically removes a specific adenine residue from a highly conserved stem-loop structure (i.e., the α-sarcin loop) in the 28S rRNA of eukaryotic ribosomes, thus interfering with Elongation Factor-2 binding and blocking cellular protein synthesis. More specifically, PAP removes an adenine base by cleavage of the N-glycosidic bond at A4324 in rat 28 S rRNA and at homologous sites on ribosomes from other organisms. See, e.g. Irvin et al., Pharmac. Ther. 55:279-302 (1992); Endo et al., Biophys. Res. Comm. 150:1032-1036 (1988); and Hartley et al., FEBS Lett. 290:65-68 (1991). PAP recognizes and binds to the ribosomal protein L3 that is essential for subsequent depurination of the α-sarcin loop. See, Hudak et al., J. Biol. Chem. 274:3859-3864 (1999). PAP protein confers resistance to a broad spectrum of viruses when expressed in crop plants, yeast and cultured human cells. Lodge et al., Proc. Natl. Acad. Sci. USA 90:7089-7093 (1993), report the Agrobacterium tumefaciens-mediated transformation of tobacco with a cDNA encoding wild-type pokeweed antiviral protein (PAP) and the resistance of the transgenic tobacco plants to unrelated viruses. Lodge also reports, however, that the PAP-expressing tobacco plants (i.e., above 10 ng/mg protein) tended to have a stunted, mottled phenotype, and that other transgenic tobacco plants that accumulated the highest levels of PAP were sterile. Since that time, Applicant has found that various PAP mutants provide comparable resistance to plant pests such as viruses and fungi but are less toxic than wild-type PAP. See, U.S. Pat. Nos. 5,756,322; 5,880,329 and 6,137,030. The PAP mutants disclosed in the prior art that exhibited less cytotoxicity (e.g., phytotoxicity) than wild-type PAP also exhibited the capability of depurinating the cell ribosomes. The belief was that cytotoxic effect was a result of translation inhibition due to depurinated rRNA. Applicants have discovered that PAP depurination can occur in the absence of cytotoxicity and that both events are independent. That is, just because a PAP protein depurinates a ribosome and thus can effectively interfere with the ability of a cell to manufacture proteins does not mean the PAP protein will also be cytotoxic. One aspect of the present invention is directed to PAP mutants that depurinate the ribosomes of the cell, but are less toxic to cells than wild type PAP. The Pokeweed Antiviral Protein (PAP) mutant is said to be substantially non-toxic and exhibits ribosome depurination activity. One preferred PAP mutant differs from wild-type PAP in that the native tyrosine residue at position 123 is replaced by alanine (hereinafter PAP (1-262, Y123A)). Other preferred PAP mutants contain PAP (1-262, S14M, Y16A), PAP (1-262, L71R), PAP (1-262, V73E), PAP (1-262, M74R), PAP (1-262, Y76A) and PAP (1-262, Y123I). Yet other preferred PAP mutants differ from wild-type PAP substantially in that they are truncated at their C-termini from 10 to 20 mature PAP amino acids. These PAP mutants are designated PAP (1-242), PAP (1-243), PAP (1-244), PAP (1-245), PAP (1-246), PAP (1-247), PAP (1-248), PAP (1-249), PAP (1-250) and PAP (1-251). DNAs encoding the PAP mutants, chimeric constructs thereof, including vectors and non-human hosts transformed with the constructs, are also provided. Another aspect of the present invention is directed to transgenic plants that express nucleic acids encoding the PAP mutants. The plants exhibit resistance to a broad spectrum of plant pests such as viruses and fungi. The invention also provides plant parts e.g., leaves, stems and shoots, as well as plant cells and protoplasts, containing a DNA molecule encoding a PAP mutant, from which whole plants expressing the DNA are generated. The invention applies to flowering plants in general, including both monocots and dicots. In preferred embodiments, the plants are corn, rice, wheat, turfgrass, soybean, cotton canola, potato, tomato and cucurbits. Seed derived from the transgenic plants is also provided. Methods of making the transgenic plants are further provided. The PAP mutants of the present invention also have utility as biotherapeutic agents. Thus, a further aspect of the present invention is directed to a fusion protein or an immunoconjugate containing the PAP mutant and a targeting moiety that binds a receptor on or in a cell. The targeting moiety is a ligand that specifically targets to infected, diseased or otherwise unwanted cells. Thus, methods of treating mammals e.g., humans, suffering from diseases characterized by the presence and/or abnormal growth of such cells are also provided. In preferred embodiments, the agent is designed to target cells infected with a virus, or a cancer cell. DNAs encoding the fusion proteins, and constructs containing the DNAs, therapeutic compositions containing the fusion proteins or immunoconjugates, and methods of using same e.g., to treat cancer or AIDS patients, are also provided. Continue reading about Non-cytotoxic pap mutants... Full patent description for Non-cytotoxic pap mutants Brief Patent Description - Full Patent Description - Patent Application Claims Click on the above for other options relating to this Non-cytotoxic pap mutants patent application. Patent Applications in related categories: 20090291893 - Compositions for the prevention and treatment of neuroinjury and methods of use thereof - A method for preventing or ameliorating secondary neuronal injury and inflammation following traumatic brain injury (TBI) is disclosed. The method comprises the step of administering into a subject in need of such treatment an effective amount of a pharmaceutical composition containing a neuregulin (NRG), a variant of NRG, or an ... 20090291885 - Conjugated toxin peptide therapeutic agents - Disclosed is a composition of matter comprising an OSK1 peptide analog, and in some embodiments, a pharmaceutically acceptable salt thereof. A pharmaceutical composition comprises the composition and a pharmaceutically acceptable carrier. Also disclosed are DNAs encoding the inventive composition of matter, an expression vector comprising the DNA, and host cells ... 20090291889 - Diagnostic assay and method of treatment for miscarriage risk or premature birth involving macrophage inhibitory cytokine-1 (mic-1) - Methods for diagnosing risk of miscarriage and/or premature birth, foetal abnormalities, cancer (e.g. prostate cancer) and inflammatory disease (e.g. rheumatoid arthritis) are disclosed which involve determining abnormal levels of macrophage inhibitory cytokine-1 (MIC-1) in a body sample or, otherwise, determining the presence of a MIC-1 variant protein. Also disclosed are ... 20090291890 - Factor vii polypeptides that are modified and uses thereof - Modified factor VII polypeptides and uses thereof are provided. Such modified FVII polypeptides include Factor VIIa and other forms of Factor VII. Among modified FVII polypeptides provided are those that have altered activities, typically altered procoagulant activity, including increased procoagulant activities. Hence, such modified polypeptides are therapeutics. ... 20090291896 - Genes encoding novel proteins with pesticidal activity against coleopterans - The invention provides nucleic acids, and variants and fragments thereof, obtained from strains of Bacillus thuringiensis encoding δ-endotoxins having pesticidal activity against pests of the order Coleoptera. The invention further provides mutagenized nucleic acids that have been modified to encode endotoxins having improved pesticidal activity and/or altered pest specificity. Particular ... 20090291895 - Methods and compositions for the treatment of inflammatory diseases - Compositions and methods for treating inflammatory disorders are provided. ... 20090291894 - Methods for treating progressive cognitive disorders related to neurofibrillary tangles - The described invention provides methods for treating or preventing progression of a progressive cognitive disease, disorder or condition, and methods for improving resilience of cognitive function in a subject in need thereof. ... 20090291897 - Methods for treating unwanted weight loss or eating disorders by administering a trkb agonist - This invention relates to methods for treating unwanted body weight loss (such as cachexia), eating disorders (such as anorexia nervosa), or opioid-induced emesis by peripheral administration of a trkB agonist. The invention also relates to compositions and kits comprising a trkB agonist. ... 20090291888 - Modulators of tnf receptor associated factor (traf), their preparation and use - A DNA sequence encoding a protein capable of binding to a tumor necrosis factor receptor-associated factor (TRAF) molecule, TRAF-binding proteins, their isoforms, analogs, fragments and derivatives encoded by the DNA sequence, their methods for the production of the DNA sequences and proteins, and the uses for the DNA sequence and ... 20090291884 - Proteins for use in diagnosing and treating infection and disease - The present invention describes a composition comprised on cystatin A and at least one histone used in diagnostic tools and for the treatment of diseases associated with reduced T helper cell counts such as HIV-1 infection, AIDS, ARC, multiple sclerosis, chronic fatigue syndrome, heumatoid arthritis, Alzheimer's disease, dermatitis, type 1 ... 20090291887 - Proteins of the sdf-1-family for the manufacturing of a medicament - Use of a protein of the SDF-1-family for the manufacturing of a medicament for the improvement of the plasticity and/or regeneration of axons upon their lesion. ... 20090291892 - Slpa as a tool for recombinant protein and enzyme technology - Disclosed are a recombinant DNA molecule encoding a fusion protein comprising a SlpA chaperone and a target polypeptide wherein human FK506 binding proteins (FKBPs) are excluded as target polypeptides, a corresponding expression vector encoding said fusion protein as well as host cells transformed with said expression vector. Also disclosed are ... 20090291886 - Transmucosal delivery of peptides and proteins - Provided are methods and compositions for enhancing the transmucosal absorption of bioactive peptides and proteins. More particularly, the invention provides compositions for enhancing the transmucosal absorption of bioactive peptides and proteins, such as exendin-4, PYY, PYY3-36, and GLP-1 and their analogs and derivatives, wherein the compositions comprise an absorption enhancing ... 20090291891 - Vegf variant that lacks vegfr-1 binding activity and its use in promotion of re-endothelization and prevention of in-stent restenosis - A VEGF145 polypeptide devoid of a VEGFR-1 binding activity and methods of making and using same in preventing and/or treating restenosis are provided. ... ###  How KEYWORD MONITOR works... a FREE service from FreshPatents1. Sign up (takes 30 seconds). 2. Fill in the keywords to be monitored. 3. Each week you receive an email with patent applications related to your keywords. Start now! - Receive info on patent apps like Non-cytotoxic pap mutants or other areas of interest. ### Previous Patent Application: Neuregulins for prevention and treatment of damage from acute assault on vascular and neuronal tissue and as regulators of neuronal stem cell migration Next Patent Application: Peptides for diagnostic and therapeutic methods for celiac sprue Industry Class: Drug, bio-affecting and body treating compositions ### FreshPatents.com Support Thank you for viewing the Non-cytotoxic pap mutants patent info. IP-related news and info Results in 2.72843 seconds Other interesting Feshpatents.com categories: Electronics: Semiconductor , Audio , Illumination , Connectors , Crypto , paws |
 * Protect your Inventions * US Patent Office filing 
PATENT INFO |
|
