Abstract: A synthetic vaccine is contemplated comprising a peptide residue coupled to one or more alkyl or alkenyl groups of at least 12 carbon atoms or other lipophilic substance wherein said peptide residue contains a sequence of 6 amino acids corresponding to the sequence of such amino acids in a protein antigen or allergen where the greatest local average hydrophilicity of the antigen or allergen is found.

Abstract: Picogram amounts of DNA can be detected in a sample by the use of high-affinity, single-stranded DNA binding proteins. The assay is applicable not only to pure DNA samples but also to samples containing significant amounts of protein.

Abstract: Disclosed is a method for preparing pertussis toxin toxoid by a treatment pertussis toxin with formaldehyde, which comprises carrying out said treatment in the presence of lysine or glycine in combination with N-acetyltriptophan. The resultant toxoid does not exhibit toxicity reversion, thereby making the toxoid highly suitable for use in pertussis vaccines.

Abstract: Composition for the prevention and treatment of autoimmune diseases are provided which comprise as an active ingredient membrane material shed from autoimmune T lymphocytes, or activated T lymphocytes which are treated by a pressure application and releases process. There is also provided processes for obtaining such active materials and for preparing pharmaceutical compositions containing them.

Abstract: The present invention relates to the immunotoxines which are obtained by the covalent coupling of, on the one hand, trichosanthin or trichokirin, as such or appropriately modified with, on the other hand, an antibody or antibody fragment, used in its natural form or correctly modified, which is capable of selectively recognizing an antigen carried by the target cells to be destroyed.

Abstract: "Iscom" adjuvant matrices, comprising a sterol, a glycoside, a solubilized water-insoluble antigen and, optionally, a phospholipid, may be formed without removing the solubilizing agent used for the antigen. The glycoside is preferably Quil A and the sterol is preferably cholesterol.

Abstract: Immunotoxins formed by the covalent coupling of, on the one hand, the A chain of ricin, as such or correctly modified, with, on the other hand, an antibody or a fragment of an antibody, used in its natural form or correctly modified, which possesses the capacity to selectively recognize an antigen carried by the intended target cells. The coupling is effected either via a disulfide bond or via a thioether bond, with the limitation that, when the coupling is effected via a disulfide and one of the sulfur atoms is that belonging to the A chain of ricin, the other sulfur is bonded to the antibody by a spacing structure which is itself bonded to a group of the protein other than an amine group.

Abstract: A method for chemically coupling a controllable number of ligands, e.g., haptens, to a polymeric material by derivatization of the polymer with an activating agent to introduce a couplable functional group. The derivatization is performed in the presence of a blocking agent which is reactive with the same functionality on the polymer as the activating agent. By reacting the polymer with a mixture of a predetermined ratio of excess amounts of the activating and blocking agents, a controllable number of couplable functional groups are introduced to the polymer for subsequent linkage to the desired ligand. The resulting polymer-ligand conjugates are useful as reagents in immunoassays, particularly immunoturbidimetric assays.

Abstract: Picogram amounts of DNA can be detected in a sample by the use of high-affinity, single-stranded DNA binding proteins. The assay is applicable not only to pure DNA samples but also to samples containing significant amounts of protein.

Abstract: The invention herein is directed to methods using Procion dyes to perform separations of interest in manipulating the NAD.sup.+ -independent ribotoxins. The methods are useful for preparing therapeutic agents containing these ribotoxins or their A polypeptide components. This separation method has been applied in particular to preparing hybrid toxins containing ricin toxins, both for purifying the resulting products and also for separating the components intended to be used in the preparation of these end products. In addition, a novel ricin isotoxin prepared using the method of the invention is disclosed.

Abstract: A new method is described for eliciting IgG antibody response to proteins or synthetic peptides without the requirement for the use of adjuvants, thereby making it easier and safer to confer protection against pathogenic organisms. The antigen is coupled to a monoclonal antibody, specific for membrane determinants expressed on certain types of mammalian recipient cells, called antigen presenting cells. The monoclonal antibody acts as a "vector" or "delivery vehicle" for targeting foreign antigens onto such recipient cells. This targeting facilitates subsequent antigen recognition by helper T-cells, which are pivotal in helping the induction of antigen-specific IgG responses.

Abstract: A liposome conjugated with a streptavidin compound, wherein carboxyl residues of the streptavidin are coupled to phospholipid amino groups of the liposome. The resultant streptavidin-conjugated liposome can be used to encapsulate drugs and cytotoxic agents for site-specific in vivo or ex corpra targeting.

Abstract: A novel hyposensitization agent was prepared by covalently attaching a saccharide, e.g. homo- and heteroglycans, for example, starch, amylose, dextran, polysucrose, pullulan, elsinan, curdlan, gum arabic, gum tragacanth, guar gum, xanthan gum carrageenan, pectin, cellulose, glucomannan, chitosan, and lipopolysaccharide, and their derivatives and partial hydrolysates to, a cedar pollen allergen. The hyposensitization agent can be administered to a cedar pollinosis patient without fear of eliciting anaphylaxis and allergy within a shortened hyposensitization period because the hyposensitization agent much more enhances the production of immunoglobulin G and M antibodies which are specific to intact cedar pollen allergen, but extremely reduces the production of immunoglobulin E antibody which is specific to the allergen and responsible for anaphylaxis and allergy.

Abstract: The present invention provides a process for the renaturation of denatured proteins in solution in a renaturation buffer, wherein a solution is prepared of the protein to be renatured in the critical concentration in a selected buffer and, after formation of the folding intermediate, further protein to be renatured is added in the amount necessary for the achievement of the critical concentration.

Abstract: There are provided anti-tumor vaccines which contain as active ingredient tumor cells which have been pressure treated so as to augment their antigenic properties, tumor cells treated with cholesteryl hemisuccinate (CHS) and subsequently pressure treated, or plasma membranes from either of, or membrane proteins shed from either of these cells, or a combination of any of these. According to another embodiment, tumor cells are treated with cholesteryl hemisuccinate or by the application and release of pressure, and subsequently with a cross-linking agent. Such cells, plasma membranes obtained from these and proteins shed from the surface of these are effective active ingredients in anti-tumor vaccines.

Abstract: A pharmaceutical composition is prepared wherein biologically active conjugated interleukin-2 is dissolved in an aqueous carrier medium without the presence of a solubilizing agent. The unconjugated IL-2, which is not water soluble or not readily soluble in water at pH 6-8 without such solubilizing agent, is selectively conjugated to one or more succinyl groups by reaction with succinic anhydride.

Abstract: This process involves the use of benzoquinone as cross-linking agent in large excess compared with the substance to be activated. The activation reaction is realized in a homogeneous liquid medium. Said process making it possible for example to couple antibodies to enzymes for determining or detecting said antibodies.The process can be used for the determination of antitetanic antibodies in human serum.

Abstract: The present invention relates to conjugates in which a monovalent carboxylic ionophore is associated by means of a covalent bond with a macromolecule chosen from antibodies, fragments of antibodies, and peptide ligands. It also relates to the activated ionophores.These conjugates are suitable as immunotoxin potentiators.

Abstract: A method is provided for detecting and measuring acetaldehyde-protein condensates. An antibody is produced to an antigen, the antibody being cross-reactive with acetaldehyde-protein condensates, these condensates including protein moieties corresponding to or different from the protein moiety of the antigen. Detection and measurement of acetaldehyde-protein condensates may be performed by reacting the antibody with the acetaldehyde-protein condensate to form a complex and measuring the complex.

Abstract: Conjugates of transferrin or ceruloplasmin with anti-tumor agents. Such conjugates are useful in the treatment of tumors. Suitable anti-tumor agents include adriamycin, daunomycin, methotrexate, vincristin, 6-mercaptopurine, cytosine arabinoside and cyclophosphamide. Transferrin or ceruloplasmin is preferably coupled to the anti-tumor agent by means of glutaraldehyde.

Abstract: This invention relates to bifunctional coupling agents useful in forming conjugates with biologically useful molecules, such as antibodies. These conjugates can be complexed with radionuclide metal ions to provide materials useful for in vivo diagnostic and therapeutic applications.

Abstract: A conjugate comprising a vinca moiety convalently linked at the 4-position via a group of the formula --OCOXCO-- where X represents a single chemical bond or an optionally substituted C.sub.1-10 chain, to an immunoglobulin or an immunoglobulin fragment.The conjugates are useful in the treatment of cancer.

Abstract: This application discloses a process for reducing methionine sulfoxide residues in peptides and proteins to methionine residues. The process comprises subjecting said peptide or protein to a substantially anhydrous trifluoroacetic acid reaction medium containing from about 0.01M to about 3M of an organic sulfide and from about 0.01M to about 3M of a haloacid selected from the group consisting of hydrochloric acid, hydrobromic acid, and hydroiodic acid.

Abstract: Covalently-modified neutral bacterial polysaccharides; covalent conjugates of such polysaccharides linked by a bigeneric spacer, with immunogenic bacterial membrane or other proteins, which conjugates are useful components of bacterial vaccines; and methods of preparing such polysaccharides and conjugates.

Abstract: A mammalian blood protein-containing composition such as whole blood, plasma, serum, plasma concentrate, cryoprecipitate, cryosupernatant, plasma fractionation precipitate or plasma fractionation supernatant substantially free of hepatitis and other lipid coated viruses with the yield of protein activity to total protein being at least 80% is disclosed. The protein-containing composition is contacted with di- or trialkylphosphate, preferably a mixture of trialkylphosphate and detergent, usually followed by removal of the di- or trialkylphosphate.

Abstract: The invention relates to a method of immunoassay for monoamines (molecules having a primary or secondary amine function) comprising chemical quantitative conversion of such amines into derivatives of higher molecular weight, which thereafter are brought into competition with radioactive analogous, or analogous carrying a tracer, for fixation to an antibody capable of recognizing all of them.

Abstract: The chemically modified protein of the present invention has a strong islet-activating activity and is lower in various side effects than non-modified IAP, so that it may be employed as a prevention and therapeutic drug for diabetes.

Abstract: Disclosed are 1,4-dihydropyridine immunogen conjugates of immunogenic carrier materials coupled to a 1,4-dihydropyridine derivative. Said conjugates are useful for the preparation of antibodies thereto which antibodies may be used in immunoassays for 1,4-dihydropyridine compounds. An affinity column useful for the purification of said antibodies is also disclosed.

Abstract: A highly sensitive, immunoassay method for determining the amount of an analyte in a sample containing a known analyte in an unknown concentration is provided. Sample; a polypeptide-labeled analog of the analyte, an antibody specific for said analyte, a polypeptide partner capable of non-covalently binding with the polypeptide-labeled analyte to form a complex having catalytic activity, and a substrate capable of being converted to a reporter molecule by the catalytic activity of said complex are brought together in a medium. The polypeptide-labeled analyte analog is capable of competitively binding to the antibody and the polypeptide partner, the antibody inhibiting the formation of a catalytically active complex in the absence of analyte, and the concentration of the antibody, polypeptide partner and polypeptide-labeled analyte are such as to cause varying amounts of analyte to be directly related to the conversion of the substrate to the reporter molecule.

Abstract: A process is provided for the production of lymphocytosis promoting factor (LPF), filamentous haemagglutinin (FHA) and at least one fimbrial agglutinogen from a liquid culture of Bordetella pertussis, which comprises the steps of (a) separating the culture into cellular and supernatant fractions, (b) concentrating the supernatant fraction, (c) fractionating the concentrated supernatant fraction to isolate LPF and FHA containing fractions, and (d) isolating at least one fimbrial agglutinogen from the cellular fraction. A vaccine composition may be produced by mixing so-produced LPF, FHA and fimbrial agglutinogens produced.

Abstract: A method of forming a therapeutic or diagnostic agent labeled with a radioactive metal ion, which comprises: contacting an unlabeled therapeutic or diagnostic agent, consisting of a substantially non-metal chelating portion and a chelating portion capable of chelating with the radioactive metal ion, with an ion transfer material having the radioactive metal ion bound thereto and having a binding affinity for the radioactive metal less than the binding affinity of the chelating portion for the radioactive metal ion, wherein prior to contacting the chelating portion is unchelated or is chelated with a second metal having a binding affinity with the chelating portion less than the binding affinity of the radioactive metal ion, whereby a radiolabeled therapeutic or diagnostic agent is formed by the contacting, and separating the radiolabeled therapeutic or diagnostic agent from the ion transfer material, is disclosed along with various components and kits useful in practicing this method and several variations th

Abstract: A method of forming a therapeutic or diagnostic agent labeled with a radioactive metal ion, which comprises: contacting an unlabeled therapeutic or diagnostic agent, consisting of a substantially non-metal chelating portion and a chelating portion capable of chelating with the radioactive metal ion, with an ion transfer material having the radioactive metal ion bound thereto and having a binding affinity for the radioactive metal less than the binding affinity of the chelating portion for the radioactive metal ion, wherein prior to contacting the chelating portion is unchelated or is chelated with a second metal having a binding affinity with the chelating portion less than the binding affinity of the radioactive metal ion, whereby a radiolabeled therapeutic or diagnostic agent is formed by the contacting, and separating the radiolabeled therapeutic or diagnostic agent from the ion transfer material, is disclosed along with various components and kits useful in practicing this method and several variations th

Abstract: A method of preparing toxoid by treating a toxin with an oxidizing agent is described. Preparation of a vaccine against pertussis in accordance with the method is illustrated.

Abstract: A lipid coupling reagent for use in coupling amine-containing molecules, such as proteins, to liposomes. The reagent includes phosphatidylethanolamine coupled to a 3-20 atom carbon-containing spacer arm terminating at a carboxyl or thiocarboxyl group. Also disclosed are liposomes prepared to include between about 1 and 20 mole percent of the coupling reagent, and liposomes containing surface arrays of proteins attached to the liposomes through the coupling reagent.

Abstract: A product and method for increasing fertility in sheep. By "increasing felity" is meant increasing the potential of a flock of sheep to multiply by increasing ovulation in ewes. The product is an immunogenic conjugate of 4-androstene-3, 17-dione and a soluble milk protein (SMP): 6-hydroxyandrost-4-ene-3, 17-dione 6-hemisuccinyl: SMP. The method comprises immunizing the ewes in a flock of sheep against 4-androstene-3, 17-dione by administering 6-hydroxyandrost-4-ene-3, 17-dione 6-hemisuccinyl SMP at the rate of 3 to 5 mg per ewe. In previously untreated ewes, two administrations are required at between 8 to 9 and 4 to 5 weeks before the planned commencement of mating. Subsequent administrations are annually and are recommended at 5 weeks before the commencement of mating.

Abstract: This application describes a process for selectively cleaving a peptide or protein at one or more of its tryptophan residues. The process comprises treating in trifluoroacetic acid said peptide or protein at a concentration of from about 0.05 mM to about 50 mM with an organic sulfoxide at a concentration of from about 0.01M to about 1M, chloride ion at a concentration of from about 0.01M to about 2M, and water at a concentration not in excess of about 10M.

Abstract: The invention relates to an immunogenic complex containing antigenic membrane proteins or peptides from viruses mycoplasmas, bacteria, parasites or animal cells or prepared synthetically or with hybride DNA technique and glycoside. The invention also relates to a process for producing the complex, whereby microorganisms, animal cells, proteins and peptides are mixed with solubilizing agents in buffered, possibly saline, solution, whereby complexes are formed between charged monomeric antigenic proteins and detergent or peptides and solubilizing agents, whereafter the charged monomeric antigenic proteins or peptides are separated from solubilizing agents in the presence of, or are separated from solubilizing agent and directly transferred to, a glycoside solution which contains one or more glycosides with hydrophobic and hydrophilic regions in a concentration of at least the critical micellular concentration, whereby a protein complex is formed, which is isolated and purified.

Abstract: A process for producing an antibody having a specificity to estriol-3-sulfate, which comprises administering a 6-substituted-estriol-3-sulfate protein conjugate of the formula: ##STR1## wherein A is .dbd.N--O-- or --O--CO--, n is an integer of 1 to 4 and --NH--P is the residue of a protein excluding a hydrogen atom in the amino form therefrom parenterally to a living body of a vertebrate animal so as to produce the antibody in the living body and collecting a body fluid comprising the antibody from the living body.

Abstract: Glycoproteinic conjugates having trivalent immunogenic activity obtained by binding, by a covalent bond, to a protein selected among CRM 197, tetanus toxoid, and pertussis toxin, at least an oligosaccharidic hapten derived from the capsular polysaccharide of a gram-positive bacterium and at least an oligosaccharidic hapten derived from the capsular polysaccharide of a gram-negative bacterium, and wherein said oligosaccharidic haptens are previously activated by introducing terminal esters.

Abstract: A method of forming a therapeutic or diagnostic agent labeled with a radioactive metal ion, which comprises: contacting an unlabeled therapeutic or diagnostic agent, consisting of a substantially non-metal chelating portion and a chelating portion capable of chelating with the radioactive metal ion, with an ion transfer material having the radioactive metal ion bound thereto and having a binding affinity for the radioactive metal less than the binding affinity of the chelating portion for the radioactive metal ion, wherein prior to contacting the chelating portion is unchelated or is chelated with a second metal having a binding affinity with the chelating portion less than the binding affinity of the radioactive metal ion, whereby a radiolabeled therapeutic or diagnostic agent is formed by the contacting, and separating the radiolabeled therapeutic or diagnostic agent from the ion transfer material, is disclosed along with various components and kits useful in practicing this method and several variations th

Abstract: A process for sulphation and phosphorylation of a protein or peptide comprising contacting said protein or peptide with sulphuric or phosphoric acid in the presence of a non-aqeuous apolar organic solvent and contacting the resultant solution with a dehydrating agent is disclosed. Non-aggregating insulin products with bioactivity may be prepared by this process.

Abstract: Vaccines for counteracting inhibition of neutrophil degranulation by pathogenic cellular microorganisms comprise one or more purines conjugated to antigenic carriers. The purines include adenine and/or guanine in the form of a base, nucleoside, or nucleotide. The vaccines can be used with cattle to increase resistance to infections by Brucella abortus (brucellosis) and/or Haemophilus somnus (thromboembolic meningoencephalitis) and related symptomatic complex.

Abstract: Covalently modified bacterial polysaccharides and proteins; covalent conjugates of such polysaccharides linked by a bigeneric spacer, which permits proof of covalency and facilitates purification of conjugated materials, with immunogenic bacterial membrane or other proteins, which conjugates are useful components of bacterial vaccines; and methods of preparing such polysaccharides, proteins and conjugates and of confirming the covalency of the linkage between polysaccharides and proteins.

Abstract: A radioactively labeled protein comprising a protein, and a radioactive nucleoside or nucleotide, the protein being covalently linked to the nucleoside or nucleotide. Advantageously the linkage is through an NH.sub.2 group of the protein and through a carbonyl group of a ring-opened sugar moiety of the nucleoside or nucleotide. The protein can be insulin, an immunoglobulin or protein A. The radioactive moiety may be a P, C, S, H, I or Hg atom. The labels can be used to indicate the presence and amount of the protein in a biological assay.

Abstract: According to the present invention there is provided an essentially pure protein found in nature in mast cells and in basophiles, which protein is involved in the transfer of calcium into such cells. Such a protein has an isoelectric point of about 3.9 and a MW about 60,000.+-.2,000, and has an amino acid composition as herein defined. There are also provided processes for the preparation of such purified protein. Such protein is of use in blocking histamine release from cells.

Abstract: The present invention relates to a process for the production of virus vaccine, comprising covalently attaching virus to saccharide to form a virus-saccharide conjugate, and harvesting the resultant conjugate. The virus vaccine, prepared according to the present invention, exhibits a higher producibility of immunoglobulin G and immunoglobulin M antibodies, while it induces less or substantially no production of immunoglobulin E antibody, in comparison with conventional-type inactivated virus vaccine; thus, the present vaccine is favorably usable for the prevention and treatment of viral diseases.

Abstract: This invention relates to an antitumor composition of anthracycline compounds bonded to hydrophilic polypeptides having a molecular weight between 10,000 and 15,000.

Abstract: A method for purification of HBs antigen, which comprises treating an HBs tigen-containing material with an acid, optionally subjecting to salting out with ammonium sulfate, and subjecting the material to a chromatography with hydroxyapatite, by which a highly purified HBs antigen suitable for the preparation of HBV vaccine or diagnostic agent can be obtained in an industrial scale. This method is particularly useful for the purification of HBs antigen-containing material produced by recombinants obtained by DNA recombination technique.

Abstract: A heterologous expression product in host cells is separated from the host cell material by suspending the material in a buffered solution, disrupting the cells and separating the product as refractile material. The refractile material can be dissolved in a strongly denaturing solution, which is then weakened while keeping the protein in solution, thereby allowing unfolding and refolding of the protein.

Abstract: Blood substitute and blood plasma expanders comprising alpha-alpha cross-linked stroma-free hemoglobin, which is substantially free of hemoglobin derivatives modified at other sites. The hemoglobin composition is intramolecularly cross-linked between Lys 99 Alpha.sub.1 and Lys 99 Alpha.sub.2.