Via Microinjection Of Dna Into An Embryo, Egg Cell, Or Embryonic Cell Patents (Class 800/25)
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Publication number: 20020013952Abstract: Transgenic non-human animals are described comprising a transgene for a species-specific pathogen and transgene(s) for at least one receptor restricting infection of the pathogen to the host species. Also described is a method for creating the transgenic non-human animal of this invention and a method for screening an agent for the ability to inhibit infection by a species-specific virus using said transgenic non-human animal. The transgenic animal of this invention has a sustained productive viral infection and does not develop a virus-specific immune response, thereby resulting in an extremely useful self-contained system to investigate the factors modulating in vivo replication of human pathogens, the pathophysiological effect of pathogen replication and production, and the effectiveness of novel therapies and vaccines modifying or inhibiting the course of pathogenesis.Type: ApplicationFiled: December 14, 1999Publication date: January 31, 2002Inventors: Harris Goldstein, Jessie B. Paul
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Patent number: 6333447Abstract: The present invention relates to transgenic models of heart failure and, more particularly, to transgenic animals and methods for testing the usefulness of chemical compounds in treating or preventing heart failure. A transgenic mouse was developed wherein Gs&agr; is selectively overexpressed approximately three-fold in the heart. Although steady state adenylyl cyclase activities are not altered, both the percent of agonist high affinity &bgr;-adrenergic receptors as well as the rate of catalyst activation are increased. In addition, physiological and pathological studies revealed that chronically-facilitated sympathetic stimulation causes adverse cardiac effects.Type: GrantFiled: March 29, 1996Date of Patent: December 25, 2001Assignees: The General Hospital Corporation, Ohio University, The Presidents and Fellows of Harvard CollegeInventors: Charles C. Homcy, Stephen F. Vatner, Thomas Wagner, Yoshihiro Ishikawa
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Patent number: 6331658Abstract: Methods to manipulate animals such as pigs, and the animals and tissues thereby derived, to reduce their immunogenicity following implantation into humans, are described. These methods are based on the discovery that certain carbohydrate structures on pig tissues, which require expression of the gene encoding the &agr; 1→3 galactosyl transferase enzyme, are targets for natural preformed antibodies of humans and elicit further antibody production in humans, while other carbohydrate structures do not or do so in a reduced amount. In the preferred embodiment, animals are produced by homologous recombination of the gene encoding &agr; 1→3 galactosyl transferase in embryonic stem cells or by microinjection into embryos of sequences eliminating or decreasing expression of &agr; 1→3 galactosyl transferase. In alternative embodiments, animals are produced having reduced amounts of &agr; 1→3 galactosyl epitopes or epitopes which are masked by sialylation or fucosylation.Type: GrantFiled: January 27, 1995Date of Patent: December 18, 2001Assignees: Integris Baptist Medical Center, Inc., Oklahoma Medical Research FoundationInventors: David K. C. Cooper, Eugen Koren
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Patent number: 6323390Abstract: A transgenic mouse, containing an oncogene or a tumor suppressor gene operably linked to a urothelium-specific promoter in its germ cells and somatic cells serves as an animal model system for human bladder cancer.Type: GrantFiled: May 22, 1998Date of Patent: November 27, 2001Assignee: New York UniversityInventors: Xue-Ru Wu, Tung-Tien Sun
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Patent number: 6316692Abstract: A composition for in vivo transfection of non-human mammalian male germ cells comprises a nucleic acid or transgene, and a gene delivery system, and optionally a protective internalizing agent, such as an endosomal lytic agent, a virus or a viral component, which is internalized by cells along with the transgene and which enhances gene transfer through the cytoplasm to the nucleus of the male germ cell. A pharmaceutical preparation and a transfer kit utilize the composition. A method for introducing a polynucleotide into non-human mammalian male germ cells comprises the administration of the composition to a non-human mammalian. A method for isolating or selecting transfected cells utilizes a reporter gene, and a method for administering transfected male germ cells utilizes male germ cells which have been transfected in vitro.Type: GrantFiled: November 13, 1998Date of Patent: November 13, 2001Inventors: Carol W. Readhead, Robert Winston
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Patent number: 6316689Abstract: The transgenic animal of this invention can be used as an animal model for renal disease, bone disease, joint disease, pulmonary disease, hyperlipidemia, arteriosclerosis, cardiac disease, diabetes, obesity, digestive organ disease, infectious disease, allergic disease, endocrine disease, dementia or cancer, or complications thereof; and provides a nonhuman transgenic mammal for the unraveling of the mechanisms of said diseases, explorations for the development of therapeutic modalities for the diseases, and the screening of candidate therapeutic drugs.Type: GrantFiled: October 27, 1999Date of Patent: November 13, 2001Assignee: Takeda Chemical Industries, Inc.Inventors: Hisao Kasuga, Masami Isaka, Kunio Matsuoka
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Patent number: 6313373Abstract: The present invention provides human involucrin (hINV) sequences having tissue specific and cell type specific promoter activity. The sequences provided herein direct expression to suprabasal cells of stratifying epithelia. The invention further provides methods for the production of transgenic animals which contain a hINV promoter sequence which directs the expression of human papillomavirus 16 oncogenes (or other oncogenes). These animals display cervical and epidermal hyperplasias as well as cancer of the trachea, esophagus, colon, epidermis, anus/rectum, lymph nodes, spleen and lung. The animals of the invention provide a useful model for screening potential anti-neoplastic compounds, carcinogens, and co-carcinogens for a number of cancers.Type: GrantFiled: October 29, 1999Date of Patent: November 6, 2001Assignee: Case Western Reserve UniversityInventors: Richard L. Eckert, James F. Crish
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Patent number: 6307121Abstract: The present invention provides transgenic fish whose somatic and germ cells contain a genomically integrated bacteriophage lambda-derived transgene construct. The transgene construct can include an excisable test nucleic acid sequence containing a heterologous mutation target nucleic acid sequence that is detectable via bioassay in a bacterial cell into which the test nucleic acid has been introduced. The frequency of mutations in the mutation target nucleic acid sequence following exposure of the transgenic fish to one or more potentially mutagenic agents can thus be evaluated.Type: GrantFiled: May 28, 1999Date of Patent: October 23, 2001Assignee: The University of Georgia Research Foundation, Inc.Inventor: Richard N. Winn
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Patent number: 6291740Abstract: The present invention provides improved methods and compositions for the generation of transgenic non-human animals. The present invention permits the introduction of exogenous nucleic acid sequences into the genome of unfertilized eggs (e.g., pre-maturation oocytes and pre-fertilization oocytes) by microinjection of infectious retrovirus into the perivitelline space of the egg. The methods of the present invention provide an increased efficiency of production of transgenic animals with a reduced rate of generating animals which are mosaic for the presence of the transgene.Type: GrantFiled: June 10, 1999Date of Patent: September 18, 2001Assignee: Wisconsin Alumni Research FoundationInventors: Robert D. Bremel, Anthony W. S. Chan, Jane C. Burns
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Patent number: 6281408Abstract: A method of producing compound transgenic animals by co-culturing embryonic stem cells with a morula is provided.Type: GrantFiled: February 20, 1998Date of Patent: August 28, 2001Assignee: Thomas Jefferson UniversityInventor: Jaspal S. Khillan
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Patent number: 6278040Abstract: In accordance with the present invention, there are provided targeted loss of function mutant mice which express less than endogenous levels of at least one member of the steroid/thyroid superfamily of receptors in at least one specific tissue type. For example, mutations in the RXR&agr; gene in mouse germlines are lethal in the embryonic stage between E13.5 and E16.5 when bred to homozygosity. The major defect responsible for this lethal effect is hypoplastic development of the ventricular chambers of the heart, which is manifest as a grossly thinned ventricular wall with concurrent defects in ventricular septation. This phenotype is identical to a subset of the effects of embryonic vitamin A deficiency, and therefore establishes RXR&agr; as a genetic component of the vitamin A signaling pathway in cardiac morphogenesis.Type: GrantFiled: February 19, 1997Date of Patent: August 21, 2001Assignees: The Salk Institute for Biological Studies, The Regents of the University of Calif.Inventors: Henry M. Sucov, Ronald M. Evans, Kenneth R. Chien
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Patent number: 6271436Abstract: Disclosed are methods for the isolation of primordial germ cells, culturing these cells to produce primordial germ cell-derived cell lines, methods for transforming both the primordial germ cells and the cultured cell lines, and using these transformed cells and cell lines to generate transgenic animals. The efficiency at which transgenic animals are generated by the present invention is greatly increased, thereby allowing the use of homologous recombination in producing transgenic non-rodent animal species.Type: GrantFiled: October 10, 1997Date of Patent: August 7, 2001Assignee: The Texas A & M University SystemInventors: Jorge A. Piedrahita, Fuller W. Bazer
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Patent number: 6271435Abstract: The present invention describes a non-human transgenic mouse that produces in its leukocytes, a recombinant human leukotriene B4 receptor (BLTR), having physiological activity of human BLTR. The transgenic mouse has stably integrated into its genome an exogenous gene construct which includes (A) 5′ expression regulating sequences, including a BLTR specific promoter, (B) DNA encoding the BLTR and a signal sequence effective in directing overexpression of the BLTR into leukocytes of the transgenic mouse and (C) 3′ regulatory sequences that result in the overexpression of the DNA in the leukocytes. In one embodiment, (A), (B), and (C) are operably linked in the gene construct to obtain production of the BLTR in the leukocytes and overexpression thereof in the transgenic mouse.Type: GrantFiled: March 14, 2000Date of Patent: August 7, 2001Assignee: Brigham & Women's Hospital, Inc.Inventor: Charles N. Serhan
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Patent number: 6262335Abstract: A transgenic non-human eukaryotic animal whose germ cells and somatic cells contain the amyloid precursor protein sequence introduced into the animal, or an ancestor of the animal, at an embryonic stage.Type: GrantFiled: February 6, 1998Date of Patent: July 17, 2001Assignees: Johns Hopkins University, Regents of the University of MinnesotaInventors: Karen Hsiao, David R. Borchelt, Sangram S. Sisodia
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Patent number: 6262337Abstract: Transgenic animals containing recombinant DNA with modified nucleotide sequence from the vascular endothelial growth factor B (VEGF-B) gene, cells and methods for producing such animals, and methods of using them to assay substances for VEGF-B-like activity.Type: GrantFiled: February 18, 1998Date of Patent: July 17, 2001Assignee: Ludwig Institute for Cancer ResearchInventors: Gabriel von Euler, Karin Aase, Christer Betsholtz, Ulf Eriksson, Milos Pekny, Samuel Gebre-Medhin, Xuri Li
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Publication number: 20010008025Abstract: Methods for preparing cell lines that contain artificial chromosomes, methods for preparation of artificial chromosomes, methods for purification of artificial chromosomes, methods for targeted insertion of heterologous DNA into artificial chromosomes, and methods for delivery of the chromosomes to selected cells and tissues are provided. Also provided are cell lines for use in the methods, and cell lines and chromosomes produced by the methods. In particular, satellite artificial chromosomes that, except for inserted heterologous DNA, are substantially composed of heterochromatin are provided. Methods for use of the artificial chromosomes, including for gene therapy, production of gene products and production of transgenic plants and animals are also provided.Type: ApplicationFiled: June 12, 1998Publication date: July 12, 2001Inventors: GYULA HADLACZKY, ALADAR A. SZALAY
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Publication number: 20010008026Abstract: The present invention relates to methods and compositions for tissue-restricted gene recombination. In particular, the present invention provides methods and compositions for tissue-restricted gene recombination in post-mitotic cells. The present invention further provides methods for gene recombination in post-mitotic cells comprising the delivery of a Cre recombinase to the target tissue to facilitate recombination in a desired target nucleic acid.Type: ApplicationFiled: June 25, 1998Publication date: July 12, 2001Inventors: MICHAEL D. SCHNEIDER, PAUL OVERBEEK, PETER FRENKEL
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Patent number: 6255554Abstract: A non-human transgenic mammalian animal, as described above, contains an exogenous double stranded DNA sequence stably integrated into the genome of the animal, which comprises cis-acting regulatory units operably linked to a DNA sequence encoding human Factor VIII protein and a signal peptide, where the cis-acting regulatory units are active in mammary gland cells and the signal peptide is active in directing newly expressed Factor VIII into the milk of the animal. The promoter may be a milk protein promoter such as for whey acidic protein, casein, lactalbumin, or beta-lactoglobulin promoter. The transgenic mammals are preferably farm animals, for example, cows, goats, sheep, rabbits and pigs. Concurrent expression of a gene for human von Willebrand's Factor into milk may be used to stabilize newly-secreted Factor VIII.Type: GrantFiled: March 4, 1999Date of Patent: July 3, 2001Assignees: American National Red Cross, Virginia Polytechnic Institute & State UniversityInventors: Henryk Lubon, William N. Drohan, William H. Velander
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Patent number: 6255555Abstract: This invention provides a transgenic mouse capable of expressing at least two cell surface membrane proteins of human T lymphocytes, transgenes for use in production of the transgenic mouse, and a method for producing the transgenic mouse using the transgenes. The cell surface membrane proteins of human T lymphocytes are associated particularly with human immunodeficiency virus (HIV) infection, and are preferably human CD4 and fusin (CXCR4). The transgenic mouse is able to inherit to its progeny a trait of expressing the cell surface membrane proteins of human T lymphocytes, thus being useful for an animal model for HIV infection and AIDS.Type: GrantFiled: April 16, 1998Date of Patent: July 3, 2001Assignee: Japan Science and Technology CorporationInventor: Shinichiro Sawada
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Patent number: 6255113Abstract: The invention relates to methods for targeting an exogenous polynucleotide or exogenous complementary polynucleotide pair to a predetermined endogenous DNA target sequence in a eukaryotic cell by homologous pairing, particularly for altering an endogenous DNA sequence, such as a chromosomal DNA sequence, typically by targeted homologous recombination. In certain embodiments, the invention relates to methods for targeting an exogenous polynucleotide having a linked chemical substituent to a predetermined endogenous DNA sequence in a metabolically active eukaryotic cell, generating a DNA sequence-specific targeting of one or more chemical substituents in an intact nucleus of a metabolically active eukaryotic cell, generally for purposes of altering a predetermined endogenous DNA sequence in the cell.Type: GrantFiled: February 8, 1995Date of Patent: July 3, 2001Assignee: SRI InternationalInventors: David A. Zarling, Elissa P. Sena
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Patent number: 6252131Abstract: The invention relates to transgenic mammals characterized by 5-HT3 receptor over-expression in the central nervous system (CNS) . The mammals have particular utility as models for studying the role of 5-HT3 receptors in the CNS, especially for the study of reward pathways for alcohol and other substances of abuse.Type: GrantFiled: October 15, 1998Date of Patent: June 26, 2001Assignee: University of New MexicoInventors: Andrea M. Allan, Sharon R. Engel, Clifford R. Lyons
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Patent number: 6252132Abstract: A mutant mouse has germ cells and somatic cells containing a mutation comprising a disruption of the endogenous &agr;4 subunit of the nicotinic acetylcholine receptor (nAChR) gene, wherein the disrupted &agr;4 subunit of the nAChR gene results in the mouse lacking detectable levels of the endogenous &agr;4 subunit of nAChR without a change in level of expression of other nAChR subunits as compared to a wild type mouse. The mutant mouse is useful for studying the roles of the various subunits of the nAChR. The results are useful in studying the antinociceptive, hypothermia, and locomotor effects of nicotine in other mammals.Type: GrantFiled: October 27, 1999Date of Patent: June 26, 2001Assignee: Institut PasteurInventors: Jean-Pierre Changeux, Lisa Marubio
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Patent number: 6248934Abstract: The invention provides methods and compositions for expressing targeted gene products in vertebrate neurons. The compositions include gene trap vectors comprising a polynucleotide comprising promoterless selectable marker and axon reporter encoding sequences, which may be operatively joined to an internal ribosome-entry site, and may comprise a splice acceptor site located 5′ to the selectable marker and axon reporter encoding sequences. The methods include methods of expressing an axon reporter in a cell by transferring the subject vectors into an embryonic stem cell and incubating the cell under conditions whereby the cell or a progeny of the cell differentiates into a neuron comprising an axon or dendrites, and the neuron expresses the axon reporter under the transcriptional control of the gene; and specifically detecting the axon reporter in the axon or dendrites. Neuronal specific expression may also be effected in disclosed binary systems.Type: GrantFiled: November 13, 1998Date of Patent: June 19, 2001Assignee: The Regents of the University of CaliforniaInventors: Marc Tessier-Lavigne, William C. Skarnes, Kevin Mitchell, Philip A. Leighton
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Patent number: 6245963Abstract: A genetically engineered mouse model that genotypically and phenotypically mimics human patients with spinal muscular atrophy. The genome of the mouse model contains at least one mutation that knockouts the native mouse Smn gene and at least one copy of human SMNC gene that functions in a murine background and compensates for the loss of the functions provided by the Smn gene. The phenotypes of said mouse model can be grouped according to their severity of pathological conditions into three types, paralleling the three types of human spinal muscular atrophy conditions. Said mouse model can be used for studying the pathophysiology of spinal muscular atrophy and for developing and testing existing and new therapeutic and diagnostic methods.Type: GrantFiled: May 25, 2000Date of Patent: June 12, 2001Assignee: Academia SinicaInventors: Hung Li, Hsiu-Mei Hsieh-Li, Jan-Gowth Chang
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Patent number: 6245966Abstract: The present application shows that the expression of Coxsackievirus and/or Adenovirus (CAR) in various lymphocyte cell lines is sufficient to facilitate the efficient transduction of these cells by adenoviruses. This property of CAR does not require its cytoplasmic domain. Use of a truncated CAR (tCAR) lacking the cytoplasmic domain has the unexpected advantage in that integrin expression is not increased in lymphocytes expressing tCAR, whereas lymphocytes expressing full-length CAR exhibit upregulated integrin expression. Further provided are transgenic mice which have been genetically engineered for tissue-specific (lymphocyte) expression of tCAR.Type: GrantFiled: March 19, 1999Date of Patent: June 12, 2001Assignee: University Technology CorporationInventor: James DeGregori
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Patent number: 6239326Abstract: A transgenic mouse characterized by a lack of endogenous SPARC expression is provided. This mouse and tissue cultures derived therefrom provide useful models for testing drugs, particularly those useful in promoting or retarding wound healing and drugs useful for treating or preventing cataracts, diabetes mellitus, or osteoporosis. Also provided are methods of treating conditions characterized by overexpression or underexpression of SPARC.Type: GrantFiled: May 5, 1999Date of Patent: May 29, 2001Assignee: The Wistar Institute of Anatomy and BiologyInventor: Chin C. Howe
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Patent number: 6225525Abstract: A transgenic mouse with alterations in an abc1 gene is prepared by introduction of an altered abc1 gene into a host animal. The resulting transgenic mice do not produce functional ABC1 protein molecules. Cells and cell lines derived from these animals also contain the altered abc1 gene.Type: GrantFiled: October 13, 1999Date of Patent: May 1, 2001Assignee: Ortho-McNeil Pharmaceutical, Inc.Inventors: Wai-Ping Leung, Trudy Christiansen-Weber, Joseph R. Voland, Per A. Peterson
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Transgenic non-human mammal expressing the DNA sequence encoding kappa casein mammary gland and milk
Patent number: 6222094Abstract: The present invention relates to an expression system comprising a DNA sequence encoding a polypeptide which ha a biological activity of human &kgr;-casein, the system comprising a 5′-flanking sequence capable of mediating expression of said DNA sequence. In preferred embodiments the 5′-flanking sequence is from a milk protein gene of a mammal such as a casein gene or whey acidic protein (WAP) gene and the DNA sequence contains at least one intron sequence. The invention further relates to DNA sequences, replicable expression vectors and cells harboring said vectors, recombinant polypeptide e.g. in glycosylated form, and milk, infant formula or nutrient supplement comprising recombinant polypeptide.Type: GrantFiled: December 6, 1994Date of Patent: April 24, 2001Assignee: Symbicom AktiebolagInventors: Lennart Hansson, Mats Strömqvist, Sven Bergström, Olle Hernell, Jan Törnell -
Patent number: 6218595Abstract: A recombinant rodent comprises cells containing a pair genomic dopamine transporter protein alleles, wherein at least one of said alleles is incapable of expressing endogenous dopamine transporter protein. The rodent may be a homozygote, where both of said alleles are incapable of expressing endogenous dopamine transporter protein, or the rodent may be a heterozygote, and one of said alleles expresses endogenous dopamine transporter protein. The rodent is preferably a mouse.Type: GrantFiled: August 14, 1998Date of Patent: April 17, 2001Assignee: Duke UniversityInventors: Bruno Giros, Mohamed Jaber, Marc G. Caron
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Patent number: 6218597Abstract: The invention provides a transgenic mouse that is a model for heart muscle disease and heart failure. Also provided are methods of using the transgenic mouse model to study heart muscle disease and heart failure and conditions and treatments related thereto.Type: GrantFiled: April 1, 1998Date of Patent: April 17, 2001Assignee: University Technology CorporationInventors: J. David Port, Michael R. Bristow
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Patent number: 6211427Abstract: Peptides can be produced in and purified from the milk of transgenic animals. The peptides are made as fusion proteins with a suitable fusion partner such as &agr;-lactalbumin, which is a natural milk protein. The fusion partner protein acts to promote secretion of the peptides and, at least in the case of &agr;-lactalbumin, allows a single-step purification based on specific affinity. The peptide is released from the purified fusion protein by a simple cleavage step and purified away from the now liberated &agr;-lactalbumin by repeating the same affinity purification method. A particular advantage of producing peptides via this route, in addition to the obvious advantages of high yield and biocompatibility, is that specific post-translational modifications, such as carboxy terminal amidation, can be performed in the mammary gland.Type: GrantFiled: October 8, 1996Date of Patent: April 3, 2001Assignee: PPL Therapeutics (Scotland) LimitedInventors: Ian Robert Cottingham, Ian Garner
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Patent number: 6207817Abstract: This present invention relates to the findings of the DNA sequences of fish insulin-like growth factor II (IGF-II) promoter regions and recombinant IGF-II promoters. These DNA sequences are capable of being expressed in eukaryotic cells and fish embryos of another fish species. The integration of the IGF-II promoter regions or recombinant IGF-II promoters into fish of another species results in the creation of a transgenic fish. The results of this invention illustrate that a fish IGF-II promoter not only can act as a growth factor to stimulate the growth and development of fish, but also is capable of being expressed in other eukaryotic cells such as in human cells.Type: GrantFiled: October 7, 1999Date of Patent: March 27, 2001Assignee: Academia SinicaInventors: Jen-Leih Wu, Jyh-Yih Chen
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Patent number: 6204432Abstract: A transgenic mouse with alterations in a PA28&bgr; gene is prepared by introduction of an altered PA28&bgr; gene into a host mouse. The resulting transgenic animals do not produce functional PA28 molecules. Cells and cell lines derived from these animals also contain the altered PA28&bgr; gene.Type: GrantFiled: August 31, 1999Date of Patent: March 20, 2001Assignee: Ortho-McNeil Pharmaceutical, Inc.Inventors: Wai-Ping Leung, Young Yang, Tobias Preckel, Per Peterson
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Patent number: 6204433Abstract: This invention relates to methods for transforming arthropods with exogenous DNA. The methods are useful for arthropods that have not previously been amenable to DNA-mediated transformation, and also provide a simpler and more efficient means of transforming arthropods than have previously been described. The method involves microinjecting a nucleic acid sequence encoding a desired trait into the reproductive tract of a female arthropod before oviposition.Type: GrantFiled: December 24, 1997Date of Patent: March 20, 2001Assignees: University of Florida, Regents of the University of CaliforniaInventors: Marjorie A. Hoy, James K. Presnail
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Patent number: 6204431Abstract: The subject invention relates to methods of producing non-human transgenic mammals which produce various oligosaccharides and glycoconjugates in their milk. Additionally, the subject invention relates to the mammals themselves, the milk which they produce, compositions comprising the milk, fractions of the milk, and the purified oligosaccharides, as well as glyconjugates, present in the milk.Type: GrantFiled: September 5, 1997Date of Patent: March 20, 2001Assignee: Abbott LaboratoriesInventors: Pedro A. Prieto, John J. Kopchick, Richard D. Cummings, James M. Pierce, David F. Smith, Kelley W. Moremen
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Patent number: 6191342Abstract: A transgenic mouse whose genome comprises the H/K-ras 4B chimeric gene to form a mammary tumor and, particularly, the expression vector producing H/K-Ras 4B chimeric protein by using MMTV (mouse mammary tumor virus) promoter. This protein contains the first 164 amino acids of the H-Ras followed by the last 24 amino acids of K-Ras 4B. The second, it relates to the transgenic mouse expressing the H/K-Ras 4B protein with a mammary tumor, and the third, the method of preparation.Type: GrantFiled: July 22, 1999Date of Patent: February 20, 2001Assignee: LG Chemical Ltd.Inventor: Tae Saeng Choi
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Patent number: 6187993Abstract: A nucleic acid construct comprising a promoter capable of directing expression in the suprabasal cells of the epidermis and means to cause expression of an integrin subunit in the suprabasal cells. Preferably the means to cause expression of an integrin subunit is an integrin subunit coding sequence. A transgenic animal which expresses an &agr; subunit and a &bgr; subunit of integrin in the suprabasal cells of the epidermis and methods for making the transgenic animals. At least some of the transgenic animals are useful models of human disease, especially psoriasis. A method of treating psoriasis comprising administering to the patient a compound which modulates integrin function.Type: GrantFiled: November 3, 1997Date of Patent: February 13, 2001Assignee: Imperial Cancer Research Technology LimitedInventors: Fiona M. Watt, Joseph M. Carroll
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Patent number: 6187992Abstract: The present invention relates to a transgenic nonhuman animal lacking native amyloid precursor protein. The transgenic mouse of the invention may be used in the study of Alzheimer's Disease and disorders involving the central nervous system.Type: GrantFiled: March 11, 1999Date of Patent: February 13, 2001Assignees: Merck & co., Inc., Merck Frosst Canada & Co.Inventors: Hui Zheng, Howard Y. Chen, Myrna E. Trumbauer, Leonardus H. T. van der Ploeg, Guy Seabrook, Dalip Sirinathsinghji
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Patent number: 6172278Abstract: Transgenic cells, transgenic mice having an Ikaros transgene and methods for the use thereof.Type: GrantFiled: July 29, 1994Date of Patent: January 9, 2001Assignee: The General Hospital CorporationInventor: Katia Georgopoulos
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Patent number: 6166289Abstract: A transgenic animal with alterations in an IRAK gene is prepared by introduction of an altered IRAK gene into a host animal. The resulting transgenic animals do not produce functional IRAK molecules. Cells and cell lines derived from these animals also contain the altered IRAK gene.Type: GrantFiled: May 13, 1999Date of Patent: December 26, 2000Assignee: Ortho-McNeil PharmacueticalsInventors: Crafford A. Harris, John J. Siekierka, Per A. Peterson, Wai-Ping Leung
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Patent number: 6166288Abstract: A method of xenotransplanting organs, tissues, cells or non-viable components which reduces or prevents antibody-mediated rejections, including hyperacute rejection, is provided wherein transgenic animals are produced that express at least one enzyme which masks or reduces the level of the antigenic Gal.alpha.(1,3)Gal or gal epitope, and at least one complement inhibitor such as CD59, DAF and/or MCP. The transgenic animals which express both a gal epitope-reducing enzyme and a complement inhibitor will have masked or reduced levels of the gal epitope and will be much less likely to produce an antibody-mediated rejection following transplantation, and the expression of the complement inhibitor will also suppress complement activation and reduce even further a severe immune reaction following the transplantation of donor organs, tissue, cells or non-viable components from the transgenic animals so produced.Type: GrantFiled: July 3, 1996Date of Patent: December 26, 2000Assignee: Nextran Inc.Inventors: Lisa E. Diamond, John S. Logan, Geurard W. Byrne, Ajay Sharma
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Patent number: 6162963Abstract: The subject invention provides non-human mammalian hosts characterized by inactivated endogenous Ig loci and functional human Ig loci for response to an immunogen to produce human antibodies or analogs thereof. The hosts are produced by multiple genetic modifications of embryonic cells in conjunction with breeding. Different strategies are employed for recombination of the human loci randomly or at analogous host loci. Chimeric and transgenic mammals, particularly mice, are provided, having stably integrated large, xenogeneic DNA segments. The segments are introduced by fusion with yeast spheroplasts comprising yeast artificial chromosomes (YACs) which include the xenogeneic DNA segments and a selective marker such as HPRT, and embryonic stem cells.Type: GrantFiled: June 5, 1995Date of Patent: December 19, 2000Assignee: Abgenix, Inc.Inventors: Raju Kucherlapati, Aya Jakobovits, Sue Klapholz, Daniel G. Brenner, Daniel J. Capon
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Patent number: 6150584Abstract: Fully human antibodies against a specific antigen can be prepared by administering the antigen to a transgenic animal which has been modified to produce such antibodies in response to antigenic challenge, but whose endogenous loci have been disabled. Various subsequent manipulations can be performed to obtain either antibodies per se or analogs thereof.Type: GrantFiled: October 2, 1996Date of Patent: November 21, 2000Assignee: Abgenix, Inc.Inventors: Raju Kucherlapati, Aya Jakobovits, Daniel G. Brenner, Daniel J. Capon, Sue Klapholz
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Patent number: 6133503Abstract: The present invention provides a mammalian artificial chromosome (MAC), comprising a centromere and a unique cloning site, said MAC containing less than 0.1% of the DNA present in a normal haploid genome of the mammalian cell from which the centromere was obtained. The invention further provides a MAC, wherein the unique cloning site is a nucleic acid sequence encoding a selectable marker. The invention also provides methods of preparing a MAC. In addition, the invention provides methods of stably expressing a selectable marker in a cell, comprising introducing a MAC containing the selectable marker into the cell. The invention also provides a cell containing a MAC expressing an exogenous nucleic acid sequence and a transgenic mammal expressing a selectable marker.Type: GrantFiled: February 17, 1998Date of Patent: October 17, 2000Assignee: The Regents of the University of CaliforniaInventor: Immo E. Scheffler
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Patent number: 6127598Abstract: The present invention features mouse models for Nkx-2.2 gene function and for Nkx-6.1 gene function, wherein the transgenic mouse is characterized by having a defect in Nkx-2.2 gene function or a defect in Nkx-6.1 gene function (where, because Nkx-2.2 acts upstream of Nkx-6.1, a defect in Nkx-2.2 gene function affects Nkx-6.1 gene function) and by having a decreased number of insulin-producing cells relative to a normal mouse. Where the transgenic mouse contains a defect in Nkx-2.2 gene function, the mouse is further characterized by a decreased number of serotonin-producing cells relative to a normal mouse. The transgenic mice may be either homozygous or heterozygous for the Nkx-2.2 or Nkx-6.1 defect.Type: GrantFiled: July 25, 1997Date of Patent: October 3, 2000Assignee: The Regents of the University of CaliforniaInventors: Michael S. German, John L.R. Rubenstein, Lori Sussel, Maike Sander, Dennis J. Hartigan-O'Connor, Roger A. Pedersen, Juanito J. Meneses
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Patent number: 6118044Abstract: Transgenic mice which constitutively express an antibody-type molecule encoded by the transgene and which has an IgE heavy chain constant region and is specific for a pre-defined antigen, provide an allergic reaction to that antigen without prior sensitization and are useful as allergy models.Type: GrantFiled: November 13, 1998Date of Patent: September 12, 2000Assignees: Sankyo Company, Limited, The Tokyo Metropolitan Institute of Medical ScienceInventors: Hajime Karasuyama, Hiromichi Yonekawa, Choji Taya, Kunie Matsuoka
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Patent number: 6114599Abstract: The present invention provides a recombinant, glucose-regulated insulin producing beta cell whose proliferation is controlled by tetracycline or a derivative thereof. The present invention also provides a method for treating a subject with diabetes using the recombinant beta cell of the present invention.Type: GrantFiled: March 19, 1998Date of Patent: September 5, 2000Assignee: Albert Einstein College of Medicine of Yeshiva UniversityInventor: Shimon Efrat
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Patent number: 6114598Abstract: The subject invention provides non-human mammalian hosts characterized by inactivated endogenous Ig loci and functional human Ig loci for response to an immunogen to produce human antibodies or analogs thereof. The hosts are produced by multiple genetic modifications of embryonic cells in conjunction with breeding. Different strategies are employed for recombination of the human loci randomly or at analogous host loci. Chimeric and transgenic mammals, particularly mice, are provided, having stably integrated large, xenogeneic DNA segments. The segments are introduced by fusion with yeast spheroplasts comprising yeast artificial chromosomes (YACs) which include the xenogeneic DNA segments and a selective marker such as HPRT, and embryonic stem cells.Type: GrantFiled: June 5, 1995Date of Patent: September 5, 2000Assignee: Abgenix, Inc.Inventors: Raju Kucherlapati, Aya Jakobovits, Sue Kalpholz, Daniel G. Brenner, Daniel J. Capon
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Patent number: 6111165Abstract: Production of human procollagen or collagen in cells which ordinarily do not produce these molecules is effected by constructing expression systems compatible with mammary glands of non-human mammals. For example, expression systems can be microinjected into fertilized oocytes and reimplanted in foster mothers and carried to term in order to obtain transgenic non-human mammals capable of producing milk containing recombinant human procollagen or collagen. Human procollagen or collagen produced in this manner can be made of a single collagen type uncontaminated by other human or non-human collagens.Type: GrantFiled: January 15, 1999Date of Patent: August 29, 2000Assignees: Cohesion Technologies, Inc., Pharming BVInventor: Richard A. Berg
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Patent number: 6100443Abstract: Genetically engineered cells are provided which can serve as universal donor cells in such applications as reconstruction of vascular linings or the administration of therapeutic agents. The cells include a coding region which provides protection against complement-based lysis, i.e., hyperacute rejection. In addition, the cell's natural genome is changed so that functional proteins encoded by either the class II or both the class I and the class II major histocompatibility complex genes do not appear on the cell's surface. In this way, attack by T-cells is avoided. Optionally, the cells can include a self-destruction mechanism so that they can be removed from the host when no longer needed.Type: GrantFiled: June 7, 1995Date of Patent: August 8, 2000Assignees: Oklahoma Medical Research Foundation, Yale UniversityInventors: Peter J. Sims, Alfred L. M. Bothwell, Eileen A. Elliot, Richard A. Flavell, Joseph Madri, Scott Rollins, Leonard Bell, Stephen Squinto