Abstract: A method is provided for preparing a pharmaceutical composition comprising: taking polyoxyethylated castor oil which if diluted 1:10 in water has a pH greater than 5 and aging the polyoxyethylated castor oil by exposing the polyoxyethylated castor oil to a gas comprising oxygen for a period of time, the exposure to the gas over the period of time causing an acidity of the polyoxyethylated castor oil to increase; and forming a pharmaceutical composition comprising the aged polyoxyethylated castor oil and a pharmaceutically active agent such as paclitaxel; wherein at least 80% of the potency of the pharmaceutically active agent is retained by the pharmaceutical composition after the pharmaceutical composition is stored for at least 7 days at 40° C.

Abstract: Amorphous forms of 9-nitrocamptothecin are provided by grinding or pulverizing different polymorphic forms of 9-nitrocamptothecin, and the polymorphic forms are characterizable as having an X-ray powder diffraction pattern with discernable diffraction lines at different °2&thgr; values for Cu K&agr; radiation having a wavelength of 1.5406 Angstrom.

Abstract: Methods, arrays and kits are provided for rapidly and efficiently identifying and quantifying multiple different activated transcription factors in a biological sample at the same time. In one embodiment, the method includes the step of mixing a library of transcription factor probes with a sample containing activated transcription factors. The transcription factor probes that have bound to the activated transcription factors may be isolated from the complexes formed between the probes and the activated transcription factors. The bound probes can be identified, for example, by using an array of hybridization probes.

Abstract: The present invention provides novel compositions and methods for protecting and promoting cell growth and restoring physiological structure and function to mucosal tissue of the body, especially mucosa in the gastrointestinal tract. The composition can be used as a pharmaceutical or nutraceutical to treat a gastrointestinal disorder or to promote general health of an animal, preferably a human. The composition is in an oral dosage form and comprises edible oil homogenized with a sterol compound at a concentration of at least 0.5% by weight and edible wax at a concentration ranging from 3% to 30% by weight. The composition can also be used to deliver other active ingredients to the gastrointestinal tract for treating various diseases.

Abstract: A method for treating a patient having a disease associated with undesirable or uncontrolled cell proliferation such as cancer and restenosis is provided. The method comprises: delivering to the patient a therapeutically effective amount of 9-nitro-20(S)-camptothecin in combination with an effective amount of an antibiotic agent such as bleomycin.

Abstract: Disclosed is a compound that includes a camptothecin conjugated to a lactone ring protecting moiety. Also disclosed are compositions and kits including the compound, and methods of making and using the compound.

Abstract: A method is provided for producing a library of mutagenized polynucleotides from a target sequence comprising (a) taking a sample comprising: (i) a target sequence including a section to be mutagenized, (ii) a library of first primers where the first primers include a first fixed sequence and a first unknown sequence 3′ to the first fixed sequence, the first unknown sequence varying within the library of first primers, and (iii) a library of second primers where the second primer include a second fixed sequence that differs from the first fixed sequence, and a second unknown sequence 3′ to the second fixed sequence, the second unknown sequence varying within the library of second primers; (b) performing one or more cycles of primer extension amplification on the sample in the presence of at least one polymerase such that a member of the library of the first primers is extended relative to the target sequence; and (c) performing one or more additional cycles of primer extension amplification on the

Abstract: A method is provided for treating a patient having a disease associated with undesirable or uncontrolled cell proliferation. The method comprises: administering to the patient an anthracycline for a period of time during which a 20(S)-camptothecin is not present in a pharmacologically active form in patient's blood; and administering a 20(S)-camptothecin to the patient.

Abstract: Methods and compositions are provided for modulating blood insulin levels of animals by targeting the gene and gene products of cathepsins, particularly cathepsins L, K, and S, and especially cathepsin L. The method comprises: administering to the animal an agent that reduces an in vivo level of cathepsin L activity such that the blood insulin level of the animal is reduced. The method can be used to treat hyperinsulinmia and related diseases such as insulin resistance, type II diabetes, and hyperglycermia.

Abstract: Compositions and methods are provided for treating diseases associated with abnormal cell proliferation such as cancer by storing inherent tumor-suppressing functions of neoplastic cells through DNA hypomethylation. The method comprises: delivering to a patient suffering from cancer a therapeutically effective amount of a DNA methylation inhibitor such as decitabine, in combination with an effective amount of an anti-neoplastic agent whose activity as an anti-neoplastic agent in vivo is adversely affected by aberrant DNA methylation. The anti-neoplastic agent can be an alkylating agent, an antibiotic agent, an antimetabolic agent, a retinoid, a hormonal agent, a plant-derived agent, an anti-angiogenesis agent and a biologic agent such as monoclonal antibody and interferon.

Abstract: Compositions, methods, and kits are provided for efficiently generating and screening a library of highly diverse protein complexes for their ability to bind to other proteins or oligonucleotide sequences. In one aspect of the invention, a library of expression vectors is provided for expressing the library of protein complexes. The library comprises a first nucleotide sequence encoding a first polypeptide subunit; and a second nucleotide sequence encoding a second polypeptide subunit. The first and second nucleotide sequences each independently varies within the library of expression vectors. In addition, the first and second polypeptide subunit are expressed as separate proteins which self-assemble to form a protein complex, such as a double-chain antibody fragment (dcFv or Fab) and a fully assembled antibody, in cells into which the library of expression vectors are introduced.

Abstract: The present invention provides an in vitro activity assay for human hepatitis B virus (HBV) DNA polymerase, which comprises using, as the 5′ oligonucleotide in PCR amplification of HBV DNA polymerase from a sample, an oligonucleotide into which has been incorporated the SP6 viral polymerase promoter, directly transcribing and translating the PCR products in the presence of a radio-labelled agent and measuring the priming of the HBV DNA polymerase. The present invention also provides the use of such an assay to assay activity of various serum samples, to screen for inhibitors of the HBV DNA polymerase and to test and/or screen potential anti-HBV drugs for their ability to inhibit DNA priming activity of human HBV DNA polymerase.

Abstract: Compositions of matter comprising a substituted cyclodextrin and cytotoxic compound, especially cytotoxic drugs such as antibiotic, anti-fungal and anti-neoplastic, drugs are claimed. The compositions cause significantly less ulceration compared to the same formulation of cytotoxic compound without cyclodextrin compound when extravasated. The compositions may also cause less vascular irritation compared to the same formulation of cytotoxic compound without cyclodextrin when administered intravenously without extravasation. Compositions of matter comprising watersoluble cytotoxic agents, especially anticancer drugs and anti-ulceration effective or anti-irritatioin effective amounts of cyclodextrin compounds are also claimed. Methods for reducing the likelihood of ulceration and or irritation when administering the compositions according to the invention are also disclosed and claimed.

Abstract: Compositions, kits, and methods are provided for use in a recombinational cloning or subcloning methods for constructing expression vectors which comprise: ligating a library of double-stranded linear donor DNAs, where each member of the library includes a donor DNA sequence, with a double-stranded linear driver DNA which includes a promoter sequence and a donor recombination site to form a single circular donor DNA, the single circular donor DNA not including an origin of replication, where the donor DNA sequence is under the transcriptional control of the promoter; and contacting the circular donor DNA and a circular acceptor acceptor vector in the presence of a recombinase to form a single fused circular vector, the circular acceptor vector comprising an origin of replication and an acceptor recombination site capable of recombining with the circular donor DNA.

Abstract: Genetic vaccines and methods are provided for enhancing the immunity of a host such as a human to one or more pathogens. In one embodiment, a recombinant benign virus is provided as the genetic vaccine. The recombinant virus comprises: an antigen sequence heterologous to the recombinant virus that encodes a viral antigen from a pathogenic virus, expression of the viral antigen eliciting an immune response directed against the viral antigen and cells expressing the viral antigen in a host upon infection of the host by the recombinant virus; and an immuno-stimulator sequence heterologous to the recombinant virus that encodes an immuno-stimulator whose expression in the host enhances the immunogenicity of the viral antigen. The recombinant virus is replication-incompetent and does not causes a malignancy naturally associated with the pathogenic virus in the host.

Abstract: A pharmaceutical formulation is provided for delivering paclitaxel in vivo comprising: paclitaxel, a water-miscible amide and a pharmaceutically-acceptable, water-miscible solubilizer selected from the group consisting of solubilizers having the general structures R1COOR2, R1CONR2, and R1COR2, wherein R1 is a hydrophobic C3-C50 alkane, alkene or alkyne and R2 is a hydrophilic moiety.

Abstract: A pharmaceutical formulation is provided for delivering paclitaxel in vivo comprising: water and micelles comprising paclitaxel and a pharmaceutically-acceptable, water-miscible solubilizer forming the micelles, the solubilizer selected from the group consisting of solubilizers having the general structures R1COOR2, R1CONR2, and R1COR2, wherein R1 is a hydrophobic C3-C50 alkane, alkene or alkyne and R2 is a hydrophilic moiety. The solubilizer is selected such that it does not have a pKa less than about 6.

Abstract: Disclosed are implants, stents, catheters, methods and kits for the local delivery of therapeutic agents that are preferentially cytotoxic or cytostatic with regards to proliferating cells to sites where proliferative cells are present.

Abstract: A polymorphic form of 9-nitrocamptothecin is provided, the polymorph being characterizable as having, by differential scanning calorimetry, an endotherm at between 149.2 and 151.2° C., an exotherm at between 162.6 and 164.6° C., and an exotherm at between 272 and 274° C.

Abstract: Liposome preparations which comprise a lipid, or lipid like compound and a 5&bgr; steroid, DHEA or an organic acid derivative of the 5&bgr; steroid or DHEA are described. The lipsome may also include an entraped aqueous portion which comprises dissolved therein the expression product of the ob gene. Methods for treating conditions including obesity,hypercorticoidism and diabetes using the liposome preparations are also claimed.