Abstract: A document construction and management system is described. In one embodiment, documents are assembled by combining one or more modules. In one embodiment, the modules are combined according to one or more construction rules. The modules can be provided to a number of subscribers, each subscriber having one or more users. Access to each of the modules can be controlled on a subscriber basis and/or on a user basis based on different users or user classes. When new modules or new versions of an existing module are added to the database of available modules, access to the new module or version can be restricted until the new modules or versions have been reviewed and accepted. During the review period, the previous version of the module is made available to users for construction of documents. In one embodiment, one or more access rules are used to control which modules are available to which users. In one embodiment, search rules are provided to facilitate searching for a desired module.

Abstract: A document construction and management system is described. In one embodiment, documents are assembled by combining one or more modules. In one embodiment, the modules are combined according to one or more construction rules. The modules can be provided to a number of subscribers, each subscriber having one or more users. Access to each of the modules can be controlled on a subscriber basis and/or on a user basis based on different users or user classes. When new modules or new versions of an existing module are added to the database of available modules, access to the new module or version can be restricted until the new modules or versions have been reviewed and accepted. During the review period, the previous version of the module is made available to users for construction of documents. In one embodiment, one or more access rules are used to control which modules are available to which users. In one embodiment, search rules are provided to facilitate searching for a desired module.

Abstract: The present invention pertains to compositions and methods for plasmid-mediated supplementation. The compositions and methods are useful for treating anemia and other effects that are commonly associated in cancer bearing animals. Overall, the embodiments of the invention can be accomplished by delivering an effective amount of a nucleic acid expression construct that encodes a GHRH or functional biological equivalent thereof into a tissue of an animal and allowing expression of the encoded gene in the animal. For example, when such a nucleic acid sequence is delivered into the specific cells of the animal tissue specific constitutive expression is achieved.

Abstract: The present invention relates to a modular electrode system, and its use, for facilitating the introduction of a macromolecule into cells of a selected tissue in a body or plant. The modular electrode system comprises a plurality of needle electrodes; a hypodermic needle; an electrical connector that provides a conductive link from a programmable constant-current pulse controller to the plurality of needle electrodes; and a power source. In a preferred embodiment of the present invention, an operator can grasp the plurality of needle electrodes that are mounted on a support structure and firmly insert the them into the selected tissue in a body or plant. The macromolecules are then delivered via the hypodermic needle into the selected tissue. The programmable constant-current pulse controller is activated and constant-current electrical pulse is applied to the plurality of needle electrodes.

Abstract: The present invention pertains to compositions and methods for plasmid-mediated supplementation. The compositions and method are useful for retarding the growth of the tumor, and retarding cachexia, wasting, anemia and other effects that are commonly associated in cancer bearing animals. Overall, the embodiments of the invention can be accomplished by delivering an effective amount of a nucleic acid expression construct that encodes a GHRH or functional biological equivalent thereof into a tissue of an animal and allowing expression of the encoded. gene in the animal. For example, when such a nucleic acid sequence is delivered into the specific cells of the tissue specific constitutive expression is achieved.

Abstract: An apparatus and a method for isolating a biologic product, such as plasmid DNA, from cells. The method involves lysing cells in a controlled manner separate insoluble components from a fluid lysate containing cellular components of interest, followed by membrane chromatographic techniques to purify the cellular components of interest. The process utilizes a unique lysis apparatus, ion exchange and, optionally, hydrophobic interaction chromatography membranes in cartridge form, and ultrafiltration. The process can be applied to any biologic product extracted from a cellular source. The process uses a lysis apparatus, including a high shear, low residence-time mixer for advantageously mixing a cell suspension with a lysis solution, a hold time that denatures impurities, and an air-sparging bubble mixer that gently yet thoroughly mixes lysed cells with a neutralization/precipitation buffer and floats compacted precipitated cellular material.

Abstract: The present invention relates to a modular electrode system, and its use, for facilitating the introduction of a macromolecule into cells of a selected tissue in a body or plant. The modular electrode system comprises a non-symmetrically arranged plurality of needle electrodes; a hypodermic needle; an electrical connector that provides a conductive link from a programmable constant-current pulse controller to the plurality of needle electrodes; and a power source. In a preferred embodiment of the present invention, an operator can grasp the plurality of needle electrodes that are mounted on a support structure and firmly insert the them into the selected tissue in a body or plant. The macromolecules are then delivered via the hypodermic needle into the selected tissue. The programmable constant-current pulse controller is activated and constant-current electrical pulse is applied to the plurality of needle electrodes.

Abstract: One aspect of the current invention is an optimized synthetic mammalian expression plasmid with a mutated origin of replication (e.g. “mut” family of plasmids). This new plasmid comprises a therapeutic element, and a replication element. The therapeutic element of the new plasmid comprises a eukaryotic promoter; a 5? untranslated region (“UTR”); a codon-optimized-eukaryotic therapeutic gene sequence; and a poly adenylation signal. The therapeutic elements of this plasmid are operatively linked and located in a first operatively-linked arrangement. Additionally, the optimized synthetic mammalian expression plasmid comprises replication elements, wherein the replication elements are operatively linked and located in a second operatively-linked arrangement. The replication elements comprise a selectable marker gene promoter, a ribosomal binding site, a selectable marker gene sequence, and an improved origin of replication.

Abstract: This invention discloses compositions and methods of: vaccinating a subject; enhancing the vaccination efficiency; preparing a subject prior to vaccination response; and improving the clinical outcome after infectious challenge in a subject that has been vaccinated. More specifically, the invention pertains to delivering into a tissue of the subject a nucleic acid expression construct that encodes a growth-hormone-releasing-hormone (“GHRH”) before or concomitantly with delivering a vaccine to the subject, wherein, GHRH is expressed in vivo in the subject, wherein the subject comprises a human, pig, cow, bird, horse or any other animal species receiving a vaccine.

Abstract: Composition and method for stimulating angiogenesis, stimulating myogenesis, upregulating angiogenic factors and angiopoietins, and treating the muscular and vascular complications of diabetes. Overall, the embodiments of the invention can be accomplished by delivering a heterologous nucleic acid sequence encoding insulin-like growth factor I (“IGF-I”) or a functional biological equivalent thereof into the cells of the subject and allowing expression of the encoded gene to occur while the modified cells are within the subject. The nucleic acid sequence maybe delivered by a vector system including a synthetic myogenic promoter and a 3? untranslated region. The preferred method to deliver the constitutive or inducible nucleic acid encoding sequences of IGF-I or the functional biological equivalents thereof is directly into the cells of the subject by the process of in vivo electroporation.

Abstract: One aspect of the current invention is a method of preventing and/or treating arthritis and/or preventing or treating lameness in a subject. Additionally, subject quality of life and welfare, and body condition scores are improved by utilizing methodology that administers the nucleic acid expression construct encoding a GHRH or functional biological equivalent to a subject through a parenteral route of administration. Following a single dose of nucleic acid expression vector, subjects are healthier and effects are demonstrated long term without additional administration(s) of the expression construct.

Abstract: One aspect of the current invention is a method designing and using species-specific or synthetic signal peptides and GHRH sequences for the purpose of preventing and/or treating chronic illness in a subject by utilizing methodology that administers a single dose of nucleic acid expression vector or nucleic acid expression construct encoding a GHRH or functional biological equivalent to a subject through a parenteral route of administration.

Abstract: An electroporation device which may be used to effectively facilitate the introduction of a macromolecule into cells of a selected tissue in a body or plant. The electroporation device comprises an electro-kinetic device (“EKD”) whose operation is specified by software or firmware. The EKD produces a series of programmable constant-current pulse patterns between electrodes in an array based on user control and input of the pulse parameters and allows the storage and acquisition of current waveform data. The electroporation device also comprises a replaceable electrode disk having an array of needle electrodes, a central injection channel for an injection needle, and a removable guide disk.

Abstract: A composition and a method of increasing growth hormone (“GH”) values in a canine or dog, and more specifically, a canine- or dog-specific growth hormone releasing hormone (“dGHRH”), or functional biological equivalent thereof. The dGHRH is an isolated composition or a nucleic acid molecule that encodes the dGHRH or functional biological equivalent. Also, a method for delivering the composition of this invention to a subject, wherein the dGHRH increases the level of growth hormone (“GH”) secretion in a recipient subject, such as a canine or dog.

Abstract: An apparatus and a method for isolating a biologic product, such as plasmid DNA, from cells. The method involves lysing cells in a controlled manner separate insoluble components from a fluid lysate containing cellular components of interest, followed by membrane chromatographic techniques to purify the cellular components of interest. The process utilizes a unique lysis apparatus, ion exchange and, optionally, hydrophobic interaction chromatography membranes in cartridge form, and ultrafiltration. The process can be applied to any biologic product extracted from a cellular source. The process uses a lysis apparatus, including a high shear, low residence-time mixer for advantageously mixing a cell suspension with a lysis solution, a hold time that denatures impurities, and an air-sparging bubble mixer that gently yet thoroughly mixes lysed cells with a neutralization/precipitation buffer and floats compacted precipitated cellular material.

Abstract: The present invention pertains to compositions and methods for plasmid-mediated supplementation. The compositions and methods are useful for treatment or prevention of kidney failure, treatment of anemia, and other conditions commonly associated with kidney failure in order to increase survival and improve welfare in subjects with chronic renal failure. Overall, the embodiments of the invention can be accomplished by delivering an isolated nucleic acid expression construct that encodes a GHRH or functional biological equivalent thereof into a tissue of a subject and allowing expression of the encoded gene in the animal. For example, when such a nucleic acid sequence is delivered into the specific cells of the subject, tissue specific constitutive expression is achieved. The embodiments of the invention also encompass delivery of a recombinant GHRH polypeptide or functional biological equivalent thereof.

Abstract: One aspect of the current invention is a method of decreasing an involuntary cull rate in farm animals, wherein the involuntary cull results from infection, disease, morbidity, or mortality. Additionally, milk production, animal welfare, and body condition scores are improved by utilizing methodology that administers the isolated nucleic acid expression construct encoding a GHRH or functional biological equivalent to an animal through a parenteral route of administration. Following a single dose of nucleic acid expression vector, animals are healthier and effects are demonstrated long term without additional administration(s) of the expression construct.

Abstract: Transgenes driven by naturally occurring cardiac promoters have relatively low levels of cardiac transgenic gene expression, and have consequently limited the use of cardiac muscle as a target for plasmid mediated gene supplementation. However, by randomly assembling motifs of E-box, MEF-2, TEF-1 and SRE elements, cardiac-specific synthetic promoter recombinant libraries have been produced. By screening hundreds of resultant clones for transcriptional activity both in vitro and in vivo, a few cardiac-specific synthetic promoters were discovered comprising a transcriptional potency that greatly exceeds the transcriptional levels obtained from natural myogenic and viral gene promoters. These promoters are used to direct the expression of desirable genes in nucleic acid expression constructs specifically to cardiac cells.

Abstract: One aspect of the current invention is an optimized synthetic mammalian expression plasmid (e.g. pAV0201). This new plasmid comprise a therapeutic element, and a replication element. The therapeutic element of the new plasmid comprises a eukaryotic promoter; a 5′ untranslated region (“UTR”); a codon-optimized-eukaryotic therapeutic gene sequence; and a poly adenylation signal. The therapeutic elements of this plasmid are operatively linked and located in a first operatively-linked arrangement. Additionally, the optimized synthetic mammalian expression plasmid comprises replication elements, wherein the replication elements are operatively linked and located in a second operatively-linked arrangement. The replication elements comprise a selectable marker gene promoter, a ribosomal binding site, and an origin of replication.

Abstract: The present invention pertains to compositions and methods for plasmid-mediated supplementation. The compositions and method are useful for retarding the growth of the tumor, and retarding cachexia, wasting, anemia and other effects that are commonly associated in cancer bearing animals. Overall, the embodiments of the invention can be accomplished by delivering an effective amount of a nucleic acid expression construct that encodes a GHRH or functional biological equivalent thereof into a tissue of an animal and allowing expression of the encoded gene in the animal. For example, when such a nucleic acid sequence is delivered into the specific cells of the animal tissue specific constitutive expression is achieved. Furthermore, external regulation of the GHRH or functional biological equivalent thereof gene can be accomplished by utilizing inducible promoters that are regulated by molecular switch molecules, which are given to the animal.