Abstract: There is disclosed an antibody and antibody-drug conjugate for targeting drug delivery as well as a class of chemicals, termed a drug-binding molecule of complementary structure (csDBM). The csDBM is designed to "fit" the drug by combining multiple non-covalent interactions between functional groups on the drug and opposing functional groups on the csDBM. The net result on the antibody-csDBM-drug conjugate is a drug stably bound to the csDBM so as not to dissociate during in vivo administration, but not so tightly bound to allow drug dissociation from the conjugate without significant loss of activity and retaining the drug's ability to bind to a higher affinity site on or within the target cell.

Abstract: A process for production of antibody conjugates which comprises modification of a part of the amino groups in an antibody or its fragment whose antigen-binding activity is lowered by the modification of its amino groups, with a reversible modifier for protein amino groups, reaction of the antibody or its fragment with a substance bearing a group reactive with the amino group and removal of the residues of the reversible modifier from the amino groups and, when necessary, the residues of the substance bearing a group reactive with the amino group in case they are introduced onto groups other than amino groups. The process according to the present invention gives antibody conjugates with retention of antigen-binding activity and these conjugates have a possibility of being used in affinity chromatography or as a diagnostic agent or a drug for cancer therapy.

Abstract: A substituted monoethylglycinexylidide or analogue is disclosed. The xylidide or analogue has the structure of FIG. 1 of the attached drawings where M is CH.sub.2 NHCH.sub.2 CH.sub.3, CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.3 or CH.sub.2 OCH.sub.2 CH.sub.3, one of Y.sup.1 and Y.sup.2 is H and the other is a protein or a fluorescein moiety chemcially bonded to the glycinexylidide or analogue moiety. Also disclosed is a method for carrying out immunoassays for MEGX, which has the structure of FIG. 3 of the attached drawings. The method for carrying out immunoassays involves using the foregoing compounds as tracers and immunogens.

Abstract: An immunogenic conjugate which is the reductive amination product of an immunogenic capsular polymer fragment having at least one reducing group and derived from a bacterial capsular polymer of a bacterial pathogen, and a bacterial toxin or toxoid. The invention also relates to methods for the preparation of the conjugates, a vaccine containing the conjugates which elicits effective levels of anti-capsular polymer antibodies in humans. Also disclosed are methods for inducing active immunization against systemic infection in young mammals caused by bacterial pathogens comprising the administration of an immunogenic amount of the abovedescribed conjugate. In a preferred embodiment, the capsular polymer fragment prior to conjugation has at least one aldehyde group at each end of the fragment. The final conjugate made with such capsular polymers has a lattice or network structure, and provides extremely high levels of anti-capsular polymer antibodies in infants.

Abstract: The invention relates to magnetic protein conjugates of the formula IM--NH--CO--(CH.sub.2).sub.n --S--P' Iwith n=1-6, preferably with a n=1 or 2 and particularly preferably with n=1, in which M is a dispersible, magnetically reacting material or particle which carries amino groups, and P' is a protein, to a process for the preparation thereof and to the use thereof for the specific removal of cells or soluble antigens, receptors, substrates, cofactors or carbohydrate determinants from aqueous salt solutions or body fluids or as part of a diagnostic method or as a diagnostic aid, preferably for the removal of cells, preferably for bone marrow depletion or for HLA typing.

Abstract: Novel compounds and methods for the formation of disulfide linkages are presented. The novel compounds employed are substituted 2-iminothiolane hydrohalide linking agents of the following formula (I): ##STR1## wherein, X is halogen;R.sub.1 is COOR.sub.5 ; halogen; nitro; unsubstituted or halogenated C.sub.1-8 alkyl; unsubstituted or halogenated C.sub.1-8 alkoxy; unsubstituted or halogenated C.sub.2-8 alkenyl; unsubstituted or halogenated C.sub.2-8 alkynyl; unsubstituted C.sub.3-8 cycloalkyl; unsubstituted aryl; aryl substituted with 1 to 3 substituents selected from halogen, amino, unsubstituted or halogenated C.sub.1-8 alkyl, or unsubstituted or halogenated C.sub.1-8 alkoxy; unsubstituted heterocycle; or heterocycle substituted with 1 to 3 substituents selected from amino, halogen, unsubstituted or halogenated C.sub.1-8 alkyl, or unsubstituted or halogenated C.sub.1-8 alkoxy;each of R.sub.2, R.sub.3 and R.sub.4 is independently hydrogen or selected from the values of R.sub.1 ; orR.sub.1 and R.sub.

Abstract: A composition and method for treating cancers characterized by over-expression of the c-fms proto-oncogene/M-CSF receptor protein are provided. The composition involves a M-CSF polypeptide cross-linked to a cytotoxic agent capable of crossing into the cytoplasm of the cell bearing the receptor and killing the cell.

Abstract: The present invention provides a chimeric protein IL4-PE40 which selectively kills IL4 receptor bearing cells. A mutant form of the protein is also provided.

Abstract: The present invention concerns novel immunogens. These immunogens comprise novel compounds which consist of an antigen or antigenic determinant couple dot an amphiphilic adjuvant molecule and optionally also free amphiphilic adjuvant molecules. An advantageous features of these novel immunogens is the presence of both an excellent immunogen activity as well as a pronounced adjuvant activity in a single complex.

Abstract: A fluorescence polarization immunoassay for detecting the presence of methadone in a test sample is provided, based upon competition between methadone and a fluorescently labeled tracer for the binding sites on an antibody specific for methadone. The concentration of methadone in the sample determines the amount of tracer that binds to the antibody. The amount of tracer-antibody complex formed can be quantitatively measured and is inversely proportional to the quantity of methadone in the sample. Tracers used as reagents and immunogens used to raise antibodies for use as reagents are also disclosed.

Abstract: A fusion protein is disclosed which comprises GM-CSF and IL-3. Such fusion proteins more biologically active than GM-CSF or IL-3 alone or GM-CSF and IL-3 combined.

Abstract: A method for conferring or increasing the antigenicity of a disulfide-crosslinked protein by treating the protein with an oxidizing agent, such as periodate, having an oxidation potential sufficient to cleave disulfide linkages. Excess oxidizing agent is then inactivated by addition of a reducing agent. The resulting protein exhibits an increase in its ability to be bound by select antibodies, particularly monoclonal antibodies directed to linear peptide epitopes in the protein.

Abstract: A protein containing at least one pendant sulfhydryl group is directly radiolabeled with a radiometal which binds tightly to sulfhydryl groups, using one or more pendant sulfhydral groups on the protein as endogenous ligands and optionally using an exogenous ligand which binds tightly to the radiometal ion to further stabilize the chelate.

Abstract: The invention concerns antigens for the production of antibodies to Platelet Activating Factor (PAF). The antigens are PAF analogues of formula (I) ##STR1## wherein X comprises a high molecular weight group, R.sup.1 is a linking group and R.sup.2 to R.sup.5 are selected from C.sub.1 to C.sub.6 alkyl.Other aspects of the invention include PAF-antibodies produced using said antigens, labelled PAF analogues, intermediates for the preparation of PAF analogues and methods and a kit for the immunoassay of PAF.

Abstract: Fluorocarbon chain-containing linking arms can be used to conjugate haptens to protein carriers such as BSA, HSA, or antibodies without recourse to harsh chemistry. In addition, .sup.19 F atoms serve as markers for quantitative estimation of bound haptens.

Abstract: Superior pharmaceutical compositions which comprise carriers coupled to epitope-bearing moieties are described. The carriers are crystalline or paracrystalline glycoproteins, especially those derived from S-layers of microbial cell walls. These conjugates are capable of eliciting the formation of antibodies as well as a T-cell response.

Abstract: An immunogenic complex comprising a peptide containing a hydrophobic tail, the peptide being adsorbed to hepatitis B virus surface antigen via the hydrophobic tail. Such complex in a immunogenically effective amount when administered with a physiologically acceptable diluent and an adjuvant can serve as a vaccine.

Abstract: The present invention relates to a novel glycoprotein, extracted from the seeds of Trichosanthes kirilowii, called: trichokirin, as well as to its modified derivatives containing a free or blocked SH group.It relates to a process for its preparation, to its use and to pharmaceutical compositions in which it is present.

Abstract: A modified pertussis toxin suitable as a pertussis vaccine having an essentially unmodified B-oligomer and a catalytic subunit which is inactivated by treatment with polyphosphate compounds, sulfhydryl reductants and mild detergents followed by modification of the activated --SH groups to inhibit ADP-ribosylating activity.

Abstract: Method for producing an immunoconjugate comprising the steps of reacting a toxin or protein with a heterobifunctional reagent having the following general formula: ##STR1## where R.sub.1 is: ##STR2## where n=1 to 10; and where R.sub.2 is selected from the group consisting of o- and p-nitrophenyl, 2-chloro-4-nitrophenyl, cyanomethyl, 2-mercaptopyridyl, hydroxybenztriazole, N-hydroxysuccinimide, trichlorophenyl, tetrafluorophenyl, 2-fluorophenyl, 4-fluoropheyl, 2,4-difluorophenyl, o-nitro-p-sulfophenyl, N-hydroxyphthalimide, N,N-diethylamino, N-hydroxypyrrolidone, tetrafluorothiophenyl, and 2,3,5,6-tetrafluorophenyl, under reactive conditions, thereby forming a derivatized toxin or protein.

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: 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: A method for the preparation of proteins in biologically active form including providing a source of protein solubilized from inclusion bodies with a cationic surfactant; providing a weak denaturing agent; and contacting the solubilized protein with the weak denaturant in water in an amount sufficient to allow the protein to remain in a biologically active form.

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: Conjugates comprising recombinant ricin toxin A chain and a binding moiety which may be an antigen binding portion selected from the group consisting of Fab, Fab' and F(ab').sub.2 fragments of monoclonal or polyclonal antibodies, hormones, lectins or other compounds that are recognized by cell receptors, are described and claimed.

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 protein conjugate or mixture useful in immunotherapy composed of a biological response modifier (BRM) and an allergen is disclosed. In use the protein conjugate or mixture is combined with a pharmaceutically acceptable carrier. Cytokines, bacterial, fungal and viral immunopotentiators and thymus hormones are disclosed as suitable BRM's for use in the invention.

Abstract: A fluorescence-labeled Fab' is produced by causing a fluorescent substance to react with a Fab', dialyzing the resultant reaction solution, allowing the dialyzate to stand at rest thereby effecting reversion of unconjugated Fab' into F(ab').sub.2 and giving rise to a reaction solution containing a fluorescence-labeled Fab' and F(ab').sub.2 and collecting the fluorescence-labeled Fab' from the reaction solution.

Abstract: A conjugate comprising a pharmaceutically useful protein linked to at least one water-soluble polymer by means of a reversible linking group.

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: 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: A process for recovering dimeric, biologically active CSF-1 from bacterially expressed recombinant CSF1 genes is described. The process comprises recovery of the solubilized monomeric form, followed by dimerization under refolding conditions and further purification of the dimer. Heterodimers may also be produced by this process.

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: Protein conjugated chelated metal radionuclides are provided for use in vivo. Intermediates are provided for preparing the polypeptide compositions efficiently.

Abstract: A substance-conjugated complement component Clq is provided. A substance such as signal emitting substances or cell function regulating substances is conjugated via a sulfur atom to at least one site of the component. The site is not involved in binding immunoglobulins. A marker-labelled complement component Clq is used for measuring a complement-binding antibody, an antigen, a neutralizing antibody or a substance produced internally of and at the surface of a cell or a microorganism by measuring the marker.

Abstract: Macromolecular monoclonal antibody compositions are provided which are capable of selectively forming stable bonds to cells having a predetermined concentration of at least one surface antigen, such concentration being greater in such cells than in other cells in the cell population, wherein the composition comprises a substrate and a plurality of monoclonal antibodies specific to said surface antigen or antigens, which antibodies are covalently bonded to the substrate.

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: 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: 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: 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: 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 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 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: Compositions containing therapeutically or immunologically active proteins are rendered substantially free from infectious agents such as viable viruses and bacteria without substantial loss of therapeutic or immunologic activity by mixing the protein composition with a complex formed from transition metal ions, such as copper ions, and an angularly-fused, polynuclear heterocyclic arene having two nitrogen atoms in a "cis-ortho" relationship, such as phenanthroline, and a reducing agent such as a thiol or ascorbic acid or ascorbate salt or mixtures of ascorbic acid or ascorbate with a thiol in amounts and at a temperature and for a time sufficient to inactivate substantially all of the viruses and bacteria contained therein. Compositions containing therapeutically active proteins substantially free from viral and bacterial infectivity, which have heretofore been unattainable, can be prepared by the method of the invention.

Abstract: A product and process for treating allergy are described. An immunotoxin specific for the IgE isotype is used to eliminate the IgE producing B-lymphocytes responsible for allergy.

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: 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 process for the purification of HBsAg is disclosed, which comprises adsorbing specifically on a carrier, in the presence of an inorganic salt in an amount of 5 to 25 W/V %, an HBsAg obtained by gene engineering.