Abstract: Prodrugs, of generic formula I, are disclosed for use in antibody directed enzyme prodrug therapy (ADEPT). The prodrugs are substrates for carboxypeptidase G2 (CPG2) and yield more active cytotoxic drugs than known products of CPG2 catalysed reactions.

Abstract: Disclosed are (A) an antibody to a peptide consisting of 8 to 9, or 12 to 14 successive amino acids from a polypeptide having nerve growth factor-like activity, (B) a method for producing the antibody, (C) a cloned hybridoma which produces the antibody, (D) a method for producing the cloned hybridoma, (E) a conjugate of the above mentioned peptide with a carrier protein, and (F) a method for purifying, and a method for detecting and assaying a polypeptide having nerve growth factor-like activity.

Abstract: The present invention relates to a method for diagnosing prostatic adenocarcinoma (CAP) in a male human patient without requiring a biopsy. The total prostate specific antigen (PSA) level in the blood or serum of the patient is measured. If the patient has a total PSA level of between 2.5 ng/ml and 20.0 ng/ml, then the free PSA level in the blood or serum of the patient is measured. The proportion of free PSA to total PSA is calculated. If this proportion is less than about 7%, then the patient is diagnosed as having CAP. The present method can also be used on patients that have a total PSA of at least 10.1 ng/ml, but have also had a negative prostate biopsy.

Abstract: The epidermal growth factor receptor (EGFR) gene is amplified in 40% of malignant gliomas and the amplified genes are frequently rearranged. The genetic alterations associated with these rearrangements are characterized in five malignant gliomas. In one tumor, the rearrangement resulted in the deletion of most of the extracytoplasmic domain of the receptor, resulting in a hybrid mRNA between new sequences and the truncated EGFR. The predicted amino acid sequence of the protein from this tumor was remarkably similar to that described for several viral erb-B oncogenes. Four other tumors were noted to have internal deletions of the EGF receptor gene. These rearrangements brought about in-frame deletions affecting either of two cysteine-rich domains in the extracytoplasmic portion of the molecule. The clonal nature of these alterations, and the fact that identical alterations were seen in more than one tumor, suggests a role for these mutant receptor proteins in tumorigenesis.

Abstract: This invention provides a family of monoclonal antibodies specific for epitopes of p110.sup.RB protein present in the nucleus. These antibodies have superior properties that prove useful for the detection of p110.sup.RB or its complexes with other cellular regulatory proteins in cells and in cell lysates. This invention also provides hybridoma cell lines that produce such monoclonal antibodies and methods of using these antibodies diagnostically, prognostically and therapeutically. Further, the invention provides a method for isolating proteins associated with p110.sup.RB proteins.

Abstract: Humanized monoclonal antibodies are provided which are specific for human IL-4 and have properties unexpectedly superior to other, previously available humanized antibodies. Single-chain binding proteins, fusion proteins, and antigenic or IL-4 binding fragments of such antibodies are also provided by this invention. Also provided are nucleic acids which encode the heavy and light chain variable regions of such monoclonal antibodies or antigenic fragments thereof; anti-idiotypic antibodies; and methods for detecting, measuring and immunopurifying human IL-4, and for blocking or mimicking the biological activity of human IL-4.

Abstract: A target-specific, cytotoxic, recombinant Pseudomonas exotoxin is described. Such toxins are made by inserting specific recognition molecules at specific cloning sites in at least domain III near the carboxyl terminus of the PE molecule. Various modifications of the carboxyl terminus of the PE molecule to increase cytotoxicity are set forth. Multifunctional, recombinant, cytotoxic fusion proteins containing at least two different recognition molecules are provided for killing cells expressing receptors to which the recognition molecules bind with specificity. Methods for producing novel recombinant PE molecules with specific properties are described.

Abstract: The present invention broadly relates to a therapeutic agent effective in mitigating disease associated with Feline Leukemia Virus (FeLV) in a feline infected with FeLV. A feline is an animal of the family Felidae. The novel therapeutic agent is composed of feline excised lymph nodes which have been subjected to mitogenic stimulation for their expansion dispersed in a pharmaceutically-acceptable carrier. Mitogenic stimulation conditions include culturing the excised lymph nodes in the presence of Interleukin-2. Optionally, culture conditions can include the presence of allogeneic or autologous FeLV tumor. The inventive therapeutic agent is prepared by excising lymph nodes from a feline infected the FeLV, mitogenically stimulating said excised lymph nodes for their expansion, and administering to the infected feline the expanded lymph nodes. Multidose regimens can be used as is necessary or desirable in convenient fashion.

Abstract: Improved Pseudomonas exotoxins of low animal toxicity and high cytocidal activity are described. Substitution of positively charged amino acid residues with an amino acid residue without a positive charge provides markedly changed exotoxins. Conjugation of the new exotoxins with suitable targeting agents provides cytocidal specificity for killing desired cellular entities.

Abstract: The present invention provides methods for preventing occurrence or progression of liver damage using hepatocyte growth factor. In the methods, a preventatively effective amount of the hepatocyte growth factor is administered to the patient. The hepatocyte growth factor can be administered, for instance, prior to administering a hepatotoxic therapy to the patient. The hepatocyte growth factor can further be administered with activin or transforming growth factor-beta to prevent liver damage. Compositions comprising hepatocyte growth factor and activin antagonist or transforming growth factor-beta antagonist are also provided by the invention.

Abstract: The present invention describes a method for controlled activation and degradation of FVII during purification whereby a solution of Factor VII is subjected to a number of chromatographic purification steps wherein Zn.sup.++ is present in at least one of the purification steps.The present invention also describes a method for controlled activation and degradation of FVII wherein a solution of FVII is applied to a number of anion exchange and immunoaffinity columns.

Abstract: The invention is directed to a peptide having the amino acid sequence of the cytoplasmic domain of integrin subunit .beta..sub.3 ', KFEEERARAKWDTVRDGAGRFLKSLV, or subsequences thereof, and the nucleic acid encoding that peptide.

Abstract: Antigen E or Amb a I of ragweed pollen has been shown to be a family or families of proteins. cDNAs encoding Amb a I, the major human allergen of ragweed and Amb a II, peptides derived from Amb a I or Amb a II, antibodies against the peptides; and methods of treating individuals for sensitivity to ragweed are disclosed.

Abstract: The present invention relates to a product and process for regulating an immune system using an immunoglobulin fusion protein capable of targeting a specific peptide precursor to a specific antigen presenting cell. Disclosed is a peptide precursor associated with an immunoglobulin molecule capable of binding to an antigen on the surface of an antigen presenting cell. Also disclosed is a nucleic acid molecule having a sequence encoding an immunoglobulin fusion protein comprising a peptide precursor and an immunoglobulin molecule. The invention is additionally directed to therapeutic reagents which can act as toleragens or immunogens useful in the regulation of an immune response.

Abstract: Anti-TNF antibodies, fragments and regions thereof which are specific for human tumor necrosis factor-.alpha. (TNF.alpha.) and are useful in vivo for diagnosis and therapy of a number of TNF.alpha.-mediated pathologies and conditions, including rheumatoid arthritis as well as polynucleotides coding for murine and chimeric antibodies, methods of producing the antibody, methods of use of the anti-TNF antibody, or fragment, region or derivative thereof, in immunoassays and immunotherapeutic approaches are provided.

Abstract: A chimaeric protein is provided, capable of forming part of a capsid assembly and comprising the amino acid sequence of the coat protein of phage MS-2, or a conservatively modified variant thereof, or sufficient of said sequence or variant to retain the capability of forming a capsid assembly, which amino acid sequence has been modified by removal of the cysteine residues present externally of the N-terminal protruberant .beta.-hairpin of the coat protein and insertion of a cysteine residue within the region corresponding to the N-terminal protruberant .beta.-hairpin.

Abstract: Disclosed are genetic sequences and their encoded amino acid sequences for two interior nuclear matrix proteins useful as markers of malignant cell types. Primary and secondary structure analysis of the proteins is presented as well as means for their recombinant production, and compositions and methods for the use of these markers in clinical assays and cancer therapies.

Abstract: The present invention is concerned with European strains of the Porcine Reproductive Respiratory Syndrome (PRRS) virus, which are attenuated, and show a characteristic reaction pattern with two monoclonal antibodies against wild-type PRRSV.The invention also relates to vaccines for the protection of pigs against PRRS, to monoclonal antibodies reactive with PRRS virus and monoclonal antibodies specifically non-reactive with the attenuated strains.

Abstract: Methods for preventing or treating inflammation are provided. Specifically, such inflammation can be effectively treated or prevented through the use of anti-ICAM-1 antibodies which have been modified to contain poly(ethylene) glycol adducts. The modification reduces the immunoreactivity of the antibodies, and thus increases the antibodies' serum half life. Methods for forming, purifying and using such modified antibodies are described.

Abstract: Methods for diagnosing pre-hypertension, hypertension, congestive cardiomyopathy, renal failure, salt-sensitivity and adenomas and endocrine cell hyperplasias are disclosed. Also disclosed are methods for monitoring hypertension therapy, congestive cardiomyopathy therapy, renal failure therapy and adenoma and endocrine cell hyperplasia therapy. These methods involve using an antibody having binding specificity to ouabain to immunologically measure the level of human ouabain in body fluid or tissue of a subject. Additionally, methods for treating a hypertensive subject by inducing passive or active immunity to human ouabain in the subject are disclosed, along with an antibody having binding specificity for ouabain.