Abstract: Compositions and methods for the treatment or prevention of Clostridium difficile infection in a subject are provided. The compositions comprise antibodies to Clostridium difficile toxin A. The methods provide for administering the antibodies to a subject in an amount effective to reduce or eliminate or prevent relapse from Clostridium difficile bacterial infection.

Abstract: Compositions and methods for the treatment or prevention of Staphyloccus aureus infection in a subject are provided. Antibody compositions comprising monoclonal antibodies to alpha-hemolysin protein are also provided. The methods provide administering a composition to the subject in an amount effective to reduce or eliminate or prevent relapse S. aureus bacterial infection and/or induce an immune response to Staphylococcus aureus alpha-hemolysin.

Abstract: Compositions and methods for the treatment or prevention of Clostridium difficile infection in a vertebrate subject are provided. The methods provide administering a composition to the vertebrate subject in an amount effective to reduce or eliminate or prevent relapse of Clostridium difficile bacterial infection and/or induce an immune response to the protein. Methods for the treatment or prevention of Clostridium difficile infection in a vertebrate are also provided.

Abstract: Compositions and methods for the treatment or prevention of Clostridium difficile infection in a subject are provided. The compositions comprise antibodies to Clostridium difficile toxin A. The methods provide for administering the antibodies to a subject in an amount effective to reduce or eliminate or prevent relapse from Clostridium difficile bacterial infection.

Abstract: Several species of bacteria capable of invasive infections, such as S. pyogenes, S. equi and P. multocida, contain hyaluronic acid (HA) in their capsules. Bacterial species such as Staphylococcus aureus and related Staphylococci have capsules that contain acidic polysaccharides. Bacterial capsule or bacterial surface binding peptides were synthesized and tested in a culture model of invasive bacterial infections, specifically translocation through polarized keratinocyte cultures. The peptides reduced the translo-cation of a variety of bacterial species, with a concomitant increase in bacterial internalization by the keratinocytes. In vivo, subcutaneous inoculation of encapsulated GAS treated with peptides delayed bacterial dissemination. In a mouse surgical wound control model infected with S. aureus, treatment with peptides reduced the numbers of bacteria and inflammation at the wound site.

Abstract: Novel hyaluronan-binding peptides are provided. The peptides are useful in preventing and treating disorders associated with altered tissue levels of hyaluronan or RHAMM, including cancer, inflammatory and autoimmune disorders and fibrotic disorders associated with tissue trauma.

Abstract: An aminopeptidase inhibitor is used when expressing heterologous protein in a bacterial host, such as Streptomyces. Use of such an inhibitor inhibits degradation of the heterologous protein by aminopeptidases. Inhibitors are designed based upon the mechanism and substrate specificity of the target protease and expressed protein.

Abstract: Therapeutic and prophylactic methods using Rh antibodies for delaying the progression of infection with the Human Immunodeficiency Virus (HIV) in a subject who is exposed to HIV, or infected by HIV.

Abstract: A recombinant DNA molecule adapted for transfection of a host cell comprising a nucleic acid molecule encoding mammalian erythropoietin or tissue plasminogen activator, an expression control sequence operatively linked thereto and at least one SAR element. The invention also relates to expression vectors having the recombinant DNA molecule and to mammalian cells transformed with the expression vector. The mammalian cells lack multiple copies of an amplified amplification gene and are capable of expressing recombinant EPO or tPA in vitro at levels of at least 1,500 u or 500 u/10.sup.6 cells in 24 hours respectively. The invention further relates to a method of expressing recombinant mammalian EPO or tPA using the expression vectors and to a transgenic non-human animal or embryo whose germ cells and somatic cells contain a DNA construct having the recombinant DNA molecule of the invention.

Abstract: A recombinant DNA molecule adapted for transfection of a host cell comprising a nucleic acid molecule encoding mammalian erythropoietin, an expression control sequence operatively linked thereto and at least one SAR element. The invention also relates to expression vectors having the recombinant DNA molecule and to mammalian cells transformed with the expression vector. The mammalian cells lack multiple copies of an amplified amplification gene and are capable of expressing recombinant EPO in vitro at levels of at least 1,500 u/10.sup.6 cells in 24 hours. The invention further relates to a method of expressing recombinant mammalian erythropoietin using the expression vectors and to a transgenic non-human animal or embryo whose germ cells and somatic cells contain a DNA construct having the recombinant DNA molecule of the invention.

Abstract: A family of proteases endogenous to Streptomyces cells degrades heterologous proteins secreted from Streptomyces host cells. The previously unidentified proteases include (1) tripeptidyl aminopeptidase--Streptomyces ("Tap"), (2) a Streptomyces protease ("Ssp") which displayed significant amino acid sequence homology to Subtilisin BPN' and showed an ability to remove tripeptides from the amino termini of proteins and peptides, and (3) other proteases derived from Streptomyces which degraded certain substrates under certain conditions. Degradation was alleviated by selective inhibition of secreted proteases or by using hosts with impaired capabilities to produce proteases. An irreversible inhibitor was designed based upon the mechanism and substrate specificity of the target protease. Hosts secreting high amounts of proteases were selected. Impaired hosts were produced by deleting or altering the nucleotide sequence for the proteases.

Abstract: A gene expression system is used to produce heterologous biologically active proteins, in particular bioactive granulocyte macrophage colony stimulating factor ("GM-CSF"), secreted from a host selected from the Streptomyces genera. The gene expression system includes a regulatory nucleotide sequence linked to a second nucleotide sequence encoding the heterologous protein. The regulatory sequence, encodes a peptide which directs the secretion of the heterologous protein in bioactive form from a host selected from the Streptomyces genera. The regulatory sequence includes a signal sequence and a promoter sequence. The second nucleotide sequence, which encodes GM-CSF or a biologically active derivative of GM-CSF, may be either natural or synthetic. In particular, the invention relates to an expression system for secreting bioactive, non-glycosylated, oxidized, therapeutically useful GM-CSF from a host selected from the Streptomyces genera.

Abstract: A family of proteases endogenous to Streptomyces cells degrade heterologous proteins secreted from Streptomyces host cells. The previously unidentified proteases include (1) tripeptidyl aminopeptidase--Streptomyces ("Tap"), (2) a Streptomyces protease ("Ssp") which displayed significant amino acid sequence homology to Subtilisin BPN' and showed an ability to remove tripeprides from the amino termini of proteins and peptides, and (3) other proteases derived from Streptomyces which degraded certain substrates under certain conditions. Degradation was alleviated by selective inhibition of secreted proteases or by using hosts with impaired capabilities to produce proteases. An irreversible inhibitor was designed based upon the mechanism and substrate specificity of the target protease. Hosts secreting high amounts of proteases were selected. Impaired hosts were produced by deleting or altering the nucleotide sequence for the proteases.

Abstract: A DNA signal sequence initially isolated from Streptomyces griseus encodes a signal peptide which directs the secretion, via a fused intermediate, of a protein from the cell within which the DNA signal sequence is expressed. The signal sequence is derived from genes encoding protease A and protease B of S. griseus. The DNA signal sequence encodes a thirty-eight amino acid signal peptide. A DNA construct, including the DNA signal sequence and a gene sequence encoding a protein, when transformed into a living cell by a suitable vector, results in the signal peptide correctly directing the secretion of a mature protein of desired structure, particularly from prokaryotic genera selected for their ability to display enzymatic activity of a type typified by, but not exclusive to, that of protein disulphide oxidoreductase, EC 5.3.4.1, more particularly in the genera Streptomyces, and most particularly in Streptomyces lividans 66.

Abstract: This invention relates to a process for amplifying a specific nucleic acid sequence. The process involves synthesizing single-stranded RNA, single-stranded DNA and double-stranded DNA. The single-stranded RNA is a first template for a first primer, the single-stranded DNA is a second template for a second primer, and the double stranded DNA is a third template for synthesis of a plurality of copies of the first template. A sequence of the first primer or the second primer is complementary to a sequence of the specific nucleic acid and a sequence of the first primer or the second primer is homologous to a sequence of the specific nucleic acid. The amplification process may be used to increase the quantity of the specific nucleic acid sequence to allow detection, or to increase the purity of the specific nucleic acid sequence as a substitute for conventional cloning methodology.

Abstract: A gene expression system is used to produce heterologous biologically active proteins, in particular bioactive granulocyte macrophage colony stimulating factor ("GM-CSF"), secreted from a host selected from the Streptomyces genera. The gene expression system includes a regulatory nucleotide sequence linked to a second nucleotide sequence encoding the heterologous protein. The regulatory sequence, encodes a peptide which directs the secretion of the heterologous protein in bioactive form from a host selected from the Streptomyces genera. The regulatory sequence includes a signal sequence and a promoter sequence. The second nucleotide sequence, which encodes GM-CSF or a biologically active derivative of GM-CSF, may be either natural or synthetic. In particular, the invention relates to an expression system for secreting bioactive, non-glycosylated, oxidized, therapeutically useful GM-CSF from a host selected from the Streptomyces genera.

Abstract: This invention relates to an improved process for amplifying a specific nucleic acid sequence. The process involves synthesizing single-stranded RNA, single-stranded DNA and Double-stranded DNA. The single-stranded RNA is a first template for a first primer, the single-stranded DNA is a second template for a second primer, and the double stranded DNA is a third template for synthesis of a plurality of copies of the first template. A sequence of the first primer or the second primer is complementary to a sequence of the specific nucleic acid and a sequence of the first primer or the second primer is homologous to a sequence of the specific nucleic acid. The improvement of the amplification process involves the addition of DMSO alone or in combination with BSA, which improves the specificity and efficiency of the amplification.