Abstract: A c143 monoclonal antibody which is used for detecting a bovine individual having a possibility of onset of bovine leukemia; a monoclonal antibody which is used for detecting a bovine individual having a possibility of onset of bovine leukemia, wherein the monoclonal antibody has the substantially same reactivity as the c143 monoclonal antibody to a bovine MHC Class II DR molecule to which a possibility of onset of bovine leukemia is attributable; and an agent for diagnosing a possibility of onset of bovine leukemia which comprises the aforementioned monoclonal antibody. Bovine individuals having a possibility of onset of bovine leukemia can be conveniently and accurately detected.

Abstract: A method of treating an ocular disorder is disclosed, comprising administering to a patient in need of such treatment, an effective amount of a sub-immunoglobulin antigen-binding molecule that is immuno-interactive with a target antigen associated with the disorder. The invention is also directed to compositions comprising this sub-immunoglobulin antigen-binding molecule and to a method of diagnosing an ocular condition using such molecule.

Abstract: A novel immunodeficiency virus is disclosed which has the designation MVP-5180/91 and which has been deposited with the European Collection of Animal Cell Cultures (ECACC) under No. V 920 52 318. The characteristic antigens which can be obtained from it and which can be employed for detecting antibodies against retroviruses which are associated with immunodeficiency diseases are also disclosed, as are the DNA and amino acid sequences of the virus.

Abstract: This invention provides methods of obtaining novel polynucleotides and encoded polypeptides by the use of non-stochastic methods of directed evolution (DirectEvolution™). A particular advantage of end-selection-based methods is the ability to recover full-length polynucleotides from a library of progeny molecules generated by mutagenesis methods. These methods include non-stochastic polynucleotide site-saturation mutagenesis (Gene Site Saturation Mutagenesis™) and non-stochastic polynucleotide reassembly (GeneReassembly™). This invention provides methods of obtaining novel enzymes that have optimized physical &/or biological properties. Through use of the claimed methods, genetic vaccines, enzymes, small molecules, and other desirable molecules can be evolved towards desirable properties. For example, vaccine vectors can be obtained that exhibit increased efficacy for use as genetic vaccines.

Abstract: Novel hapten-carrier conjugates are capable of inducing the production of antibodies, in vivo, that specifically bind to nicotine. These conjugates comprise a nicotine hapten conjugated to an immunogenic carrier protein. The novel conjugates preserve the chirality of nicotine in its native (S)-(−) state, and have good stability properties. The conjugates are useful in formulating vaccines for active immunization, that are used to prevent and treat nicotine addiction. The antibodies raised in response to the nicotine hapten-carrier conjugate are used for passive immunization. These antibodies are administered for prevention and treatment of nicotine addiction.

Abstract: Aminoalkyl glucosaminide phosphate (AGP) compounds that are adjuvants and immunoeffectors are described and claimed. The compounds have a 2-deoxy-2-amino glucose in glycosidic linkage with an aminoalkyl (aglycon) group. Compounds are phosphorylated at the 4 or 6 carbon on the glucosaminide ring and comprise three 3-alkanoyloxyalkanoyl residues. The compounds augment antibody production in immunized animals as well as stimulate cytokine production and activate macrophages. Methods for using the compounds as adjuvants and immunoeffectors are also disclosed.

Abstract: Disclosed is a rapid and facilitated method of producing from a parentlal template polynucleotide, a set of mutagenized progeny polynculeotides whereby at each original codon position there is produced at least one substitute codon encoding each of the 20 naturally encoded amino acids. Accordingly, there is also provided a method of producing from a parental template polypeptide, a set of mutagenized progeny polypeptides wherein each of the 20 naturally encoded amino acids is represented at each original amino acid position. The method provided is termed site-saturation mutagenesis, or simply saturation mutagenesis, and can be used in combination with other mutagenization processes, such as, for example, a process wherein two or more related polynucleotides are introduced into a suitable host cell such that a hybrid polynucleotide is generated by recombination and reductive reassortment.

Abstract: LPS preparations, isolated from gram negative bacterial strains that contain at least one mutation in at least one of the htrB and msbB genes, and methods and therapeutics related thereto. The LPS preparations display both LPS antagonist and adjuvant activities.

Abstract: The present invention relates to multi-drug resistance, specifically to multi-drug resistant protein 4 (MRP4) and uses thereof. The present invention provides nucleic acid encoding MRP4, MRP4 protein, antibody reactive to MRP4 and discloses MRP4 as perhaps the first mammalian efflux pump described for nucleoside analogs. The present invention provides the first example of a role of MRP4 in drug resistance. Certain patients who develop drug resistance to anti-microbial therapy or anti-cancer therapy may develop cellular resistance mediated by MRP4. Accordingly, the present invention possesses both diagnostic and therapeutic utility as diagnostic kits, including drug assays and screens are contemplated, as well as pharmaceutical compositions and the corresponding methods of their respective use. For example, a diagnostic kit is disclosed that may be used in order to facilitate determination of patient susceptibility to MRP4 mediated drug resistance.

Abstract: Cell-free systems which effect the production of polyketides employing modular polyketide synthases are described. Libraries of new and/or known polyketides may also be produced in cell-free systems employing aromatic PKS, modular PKS or both.

Abstract: This invention provides methods of obtaining novel polynucleotides and encoded polypeptides by the use of non-stochastic methods of directed evolution (DirectEvolution™). A particular advantage of end-selection-based methods is the ability to recover full-length polynucleotides from a library of progeny molecules generated by mutagenesis methods. These methods include non-stochastic polynucleotide site-saturation mutagenesis (Gene Site Saturation Mutagenesis™) and non-stochastic polynucleotide reassembly (GeneReassembly™). This invention provides methods of obtaining novel enzymes that have optimized physical &/or biological properties. Through use of the claimed methods, genetic vaccines, enzymes, small molecules, and other desirable molecules can be evolved towards desirable properties. For example, vaccine vectors, can be obtained that exhibit increased efficacy for use as genetic vaccines.

Abstract: This invention provides an immunoconjugate which comprises 1) a non-peptidyl toxin and 2) a CD4-gamma2 chimeric heavy chain homodimer linked thereto. This invention also provides an immunoconjugate which comprises 1) a gamma radiation-emitting radionuclide of low to moderate cytotoxicity and 2) a CD4-gamma2 chimeric heavy chain homodimer linked thereto. This invention further provides an immunoconjugate which comprises 1) a non-peptidyl toxin and 2) a heterotetramer comprising two heavy chains and two light chains, both heavy chains being either a) IgG2 heavy chains or b) chimeric CD4-IgG2 heavy chains, and both light chains being either a) kappa light chains or b) chimeric CD4-kappa light chains.

Abstract: First generation adenoviral vectors and associated recombinant adenovirus-based HIV vaccines which show enhanced stability and growth properties and greater cellular-mediated immunity are described within this specification. These adenoviral vectors are utilized to generate and produce through cell culture various adenoviral-based HIV-1 vaccines which contain HIV-1 gag, HIV-1 pol and/or HIV-1 nef polynucleotide pharmaceutical products, and biologically relevant modifications thereof. These adenovirus vaccines, when directly introduced into living vertebrate tissue, preferably a mammalian host such as a human or a non-human mammal of commercial or domestic veterinary importance, express the HIV1-Gag, Pol and/or Nef protein or biologically modification thereof, inducing a cellular immune response which specifically recognizes HIV-1.

Abstract: The invention concerns the use of nucleotide analogues, defined as molecules acceptable as substrate of the reverse-transcription response and enabling the addition of at least one supplementary nucleotide to the polynucleotide chain during synthesis to affect and/or take over control of the fidelity and execution of the reverse transcription. The invention also concerns a pharmaceutical composition containing said nucleotide analogues.

Abstract: Polyenv vaccines are provided that comprise mixtures of at least 4 to about 10,000 different recombinant viruses that each express a different HIV env variant or a portion thereof containing both constant and variable regions, as well as methods of making and using such polyenv vaccines and viruses, including the use of the polyenv vaccine, in live, attenuated or inactivated form, for prophylaxis or treatment of HIV infection. The viral vaccines of the invention are optimally combined with a recombinant HIV env booster, or a recombinant HIV env gene DNA priming or boosting vaccine.

Abstract: The ICP4 protein of herpes simplex virus plays an important role in the transactivation of viral genes. The present invention discloses that ICP4 also has the ability to inhibit apoptosis. This function appears to reside in functional domain distinct from the transactivating function, as indicated by studies using temperature sensitive mutants of ICP4 that transactivating function at elevated temperatures. Also disclosed are methods for inhibition of apoptosis using ICP4 or an ICP4 encoding gene, such as an &agr;4 gene, methods of inhibiting ICP4's apoptosis-inhibiting function, and methods for the production of recombinant proteins and treatment of HSV infections.

Abstract: The present invention relates to recombinant negative strand RNA molecules which may be used to express heterologous proteins in animal cells and/or to construct recombinant viruses able to express heterologous proteins during their multiplication in host animal cells.

Abstract: A method of producing an adeno-associated virus (AAV) in an insect cell comprising (i) providing at least one insect cell-compatible vector comprising a first nucleotide sequence comprising at least one AAV ITR nucleotide sequence, a second nucleotide sequence containing an open reading frame encoding AAV VP1, VP2, and VP3 capsid proteins, a third nucleotide sequence comprising a Rep52 or a Rep40 coding sequence, and a fourth nucleotide sequence comprising a Rep78 or a Rep68 coding sequence, (ii) introducing the at least one insect cell-compatible vector into an insect cell, and (iii) maintaining the insect cell under conditions such that AAV is produced. Also provided are recombinant AAV made in accordance with the method, insect cell-compatible vectors, and insect cells comprising nucleotide sequences for production of AAV in an insect cell.

Abstract: This invention relates to an expression vector wherein said expression vector comprises a polynucleotide promoter sequence, a polynucleotide encoding a signal sequence, a polynucleotide encoding an antigen protein or peptide, a polynucleotide encoding a cell binding element, and a polynucleotide polyadenylation sequence all operatively linked. More particularly, it relates to the method of eliciting an immune response directed against an antigen in a mammal comprising the steps of introducing the expression vector into a cell, expressing the vector to produce an antigen under conditions wherein the antigen is secreted from the cell, endocytosing the secreted antigen into the cell, processing the antigen, and presenting fragments to a receptor to elicit a T-cell response. In addition, this invention relates to a vaccine and a method of use. The invention also relates to the method of identifying MHC-II restricted epitopes.

Abstract: The present invention is directed to novel artificial T helper cell epitopes (Th epitopes) designed to provide optimum immunogenicity when used in peptide immunogens comprising B cell epitopes or peptide haptens, a target antigenic site of a target antigen for eliciting antibodies thereto. The artificial Th epitopes are covalently linked to the target antigenic site and and optionally an immunostimulatory sequence to provide effective and safe peptide immunogens.