Abstract: Compositions containing alpha interferon conjugated to a substantially non-antigenic polymer are disclosed in which at least about 30% of the conjugates include covalent attachment of the alpha interferon to the substantially non-antigenic polymer at a histidine. Also disclosed is a process for preparing the conjugates. The process includes contacting an alpha interferon with a succinimidyl carbonate-activated substantially non-antigenic polymer at a pH which is sufficient to facilitate covalent attachment of the polymer on a histidine of the alpha interferon.

Abstract: A matrix and a method for preparing it are provided to support the growth of tissue, such as bone, cartilage or soft tissue. A polysaccharide is reacted with an oxidizing agent to open sugar rings on the polysaccharide to form aldehyde groups. The aldehyde groups are reacted to form covalent linkages to collagen.

Abstract: Compositions containing alpha interferon conjugated to a substantially non-antigenic polymer are disclosed in which at least about 30% of the conjugates include covalent attachment of the alpha interferon to the substantially non-antigenic polymer at a histidine. Also disclosed is a process for preparing the conjugates. The process includes contacting an alpha interferon with a succinimidyl carbonate-activated substantially non-antigenic polymer at a pH which is sufficient to facilitate covalent attachment of the polymer on a histidine of the alpha interferon.

Abstract: The invention relates to novel modified polypeptides, with or without variations in noncoding regions, with altered biological activity. The invention discloses methods of preparing the modified polypeptides and methods of use.

Abstract: Hepatic-directed compounds, reagents useful in making such compounds and associated methods and compositions are discussed. Hepatic-directed compounds are processed by metabolic mechanisms, which generally differ in degree or in kind from the metabolic mechanisms encountered by compounds which are not so directed. Reagents useful in the preparation of hepatic-directed compounds include a hexose cluster characterized by multiple hexose residues connected in an iteratively branched configuration. In one embodiment, the hexose cluster comprises at least four hexose residues with each branch of the configuration having two prongs. In another embodiment, the hexose cluster comprises at least nine hexose residues with each branch of the configuration having three prongs.

Abstract: A matrix and a method for preparing it are provided to support the growth of bone or cartilage tissue. A polysaccharide is reacted with an oxidizing agent to open sugar rings on the polysaccharide to form aldehyde groups. The aldehyde groups are reacted to form covalent linkages to collagen.

Abstract: The invention relates to a process for producing an immunogenic construct comprising activating at least one first carbohydrate-containing moiety with CDAP, CTEA or pNPC, and covalently joining the activated first moiety to a second moiety. Preferably, the first moiety is a polysaccharide and the second moiety is a protein. Immunogenic constructs are prepared by this process using either direct or indirect conjugation of the first and second moieties.

Abstract: Modified polypeptides with increased biological activity exhibited as either increased potency or prolonged circulating half-life are disclosed with methods of preparing the modified polypeptides and methods of use.

Abstract: The invention relates to a process for producing an immunogenic construct comprising activating at least one first carbohydrate-containing moiety with CDAP, and covalently joining the activated first moiety to a second moiety. Preferably, the first moiety is a polysaccharide and the second moiety is a protein. Immunogenic constructs are prepared by this process using either direct or indirect conjugation of the first and second moieties.

Abstract: Neisseria meningitidis group B polysaccharide (GBMP) modified by having sialic acid residue N-acetyl groups replaced by N-acyl groups exhibits enhanced immuno response thereto. In addition, induction of antibodies which cross-react with unmodified group B meningococcal and E. coli K1 capsular polysaccharide and other tissue cells having a common epitope is minimized. Conjugation of the modified polysaccharides with a physiologically acceptable protein such as tetanus toxoid induces the production of specific protective antibodies with negligible levels of GBMP-cross reactive antibodies, to thereby afford protection against infections caused by group B meningococci and E. coli K1.

Abstract: The present invention provides novel conjugates of a synthetic polypeptide containing RGD or (dR)GD and a biodegradable polymer, hyaluronate. The conjugates are prepared by any one of three different methods provided by the present invention: (1) an epoxide method (2) a sodium periodate method, and (3) a tresyl chloride method. The conjugates prepared by these methods are useful to aid in wound healing and tissue regeneration by providing a temporary matrix for tissue repair. The invention also provides novel RGD-peptides.

Abstract: This invention is directed to novel nucleophilic polysubstituted aryl acridinium conjugates and the methods for preparation thereof. The novel nucleophilic polysubstituted aryl acridinium conjugates are useful in biological assays, including novel assays for the determination of Vitamin B.sub.12, folate, cortisol, estradiol, and thromboxane B.sub.2.

Abstract: This invention relates to a method of producing peracetyloxazolines from peracetyl saccharides. The method involves reacting the starting material, a peracetyl saccharide, with a reagent combination, to directly produce the peracetyl oxazoline. This method may be used for the activation of oligosaccharides, wherein an oligosaccharide containing a reducing GlcNAc terminus is activated by the formation of an oxazolide at the terminal GlcNAc, and then coupled with a bifunctional spacer to provide an oligosaccharide-spacer conjugate. The activated oligosaccharide-spacer conjugate is then coupled to a protein, such as granulocyte colony stimulating factor or .gamma.-interferon, providing a neoglycoprotein conjugate. The invention provides a method for forming neoglycoprotein conjugates which may improve biological and physiochemical properties of the protein. For example, serum lifetime or efficiency of drug delivery of the peptide to a target organ or cell may be improved.

Abstract: Disclosed is a sugar-modified cytokine which ensures migration of almost all of the dose of cytokine to the liver rapidly after administration to the live body and which can be advantageously used to enhance the effect of liver disease therapy and mitigate side effects.

Abstract: A polypeptide having a molecular weight of 40,000.+-.5,000 daltons and an isoelectric point of 9.5.+-.0.5 is prepared from a cedar pollen. The polypeptide which induces pollenosis can be suitably used as desensitization agent because it induces immunoglobulin antibody which is effective for desensitization, but does not substantially induce immunoglobulin E antibody, a major factor causative of side effects including anaphylaxis shock. Therefore, the polypeptide can be advantageously used in the treatment, prevention and/or diagnosis of pollenosis.

Abstract: A novel conjugate vaccine comprising partially hydrolyzed, highly purified, capsular polysaccharide (Ps) from Streptococcus pneumoniae bacteria (pneumococci, Pn) linked to an immunogenic carrier protein, is produced by a new process. The conjugate is useful in the prevention of pneumococcal infections. Vaccines comprising a mixture of from one to ten different pneumococcal polysaccharide-immunogenic protein (Pn-Ps-PRO) conjugates induce broadly protective recipient immune responses against the cognate pathogens from which the polysaccharide components are derived. Young children and infants younger than 2 years old, normally unable to mount a protective immune response to the Pn-Ps alone, exhibit protective immune responses upon vaccination with these Pn-Ps-PRO conjugates.

Abstract: Modified polypeptides with increased biological activity exhibited as either increased potency or prolonged circulating half-life are disclosed with methods of preparing the modified polypeptides and methods of use.

Abstract: Neisseria meningitidis group B polysaccharide (GBMP) modified by having sialic acid residue N-acetyl groups replaced by N-acyl groups exhibits enhanced immuno response thereto. In addition, induction of antibodies which cross-react with unmodified group B meningococcal and E. coli K1 capsular polysaccharide and other tissue cells having a common epitope is minimized. Conjugation of the modified polysaccharides with a physiologically acceptable protein such as tetanus toxoid induces the production of specific protective antibodies with negligible levels of GBMP-cross reactive antibodies, to thereby afford protection against infections caused by group B meningococci and E. coli K1.

Abstract: Water soluble reagents are claimed, comprising a water-soluble polymeric carrier molecule having attached thereto more than one connecting moiety wherein the connecting moiety is derived from divinyl sulfone, and wherein each connecting moiety is attached to a reactive functional group on the polymeric molecule, and wherein the reagents are capable of reaction with a molecular species having a functional group which is reactive towards the terminal vinyl group of the more than one connecting moiety and the molecular species is selected from the group consisting of labelling species, marking species, and targeting species.

Abstract: A proteinaceous product comprises a stable, substantially clear, thermally irreversible gel formed by the reaction product of protein and reducing sugar, preferably containing from 2 to 25% gel-forming protein by weight. Particles or pieces of edible material may be embedded in the gel, or the gel may be divided into pieces and incorporated as an ingredient in a food product, and the product can be rendered commercially sterile while remaining substantially clear. Such products can be produced by a process which comprises reacting an aqueous dispersion of a protein or proteinaceous material with a reducing sugar or source thereof in the presence of a denaturing agent (e.g. a chaotropic agent), and/or denaturing conditions (e.g. alkaline pH).

Abstract: A water-soluble protein conjugate modified by saccharides is covalently bound to a carbohydrate backbone via a saccharide group. Such protein conjugates modified by saccharides can be produced in a simple way by polymerizing a vinylsaccharide and conjugating in a known way the poly(vinylsaccharide) obtained in this way with the protein, which is preferably an enzyme. The protein conjugates according to the present invention are stable over long time periods at a high enzymatic activity and also in aqueous solution and are thus particularly suitable for use in test kits.

Abstract: A variety of conjugates useful for the treatment of infections due to pathogenic microorganisms are provided. The conjugates comprise at least one agent coupled to a receptor which binds a microorganism. Suitable agents include anti-infectives, such as antibiotics and synthetic drugs. The present invention also provides methods for treating infections in warm-blooded animals due to pathogenic microorganisms.

Abstract: A stabilized conjugated peptide complex comprising a peptide conjugatively coupled to a polymer including lipophilic and hydrophilic moieties, wherein the peptide may, for example, be selected from the group consisting of insulin, calcitonin, ACTH, glucagon, somatostatin, somatotropin, somatomedin, parathyroid hormone, erythropoietin, hypothalamic releasing factors, prolactin, thyroid stimulating hormones, endorphins, enkephalins, vasopressin, non-naturally occurring opioids, superoxide dismutase, interferon, asparaginase, arginase, arginine deaminease, adenosine deaminase, ribonuclease, trypsin, chymotrypsin, and papain.

Abstract: The present invention relates to a method of producing an E. coli vaccine and to the vaccine produced thereby. The method involves purifying lipopolysaccharide from E. coli expressing complete O-polysaccharide sidechains;isolating the O-polysaccharide region of the lipopolysaccharide molecule by hydrolysis in dilute acetic acid and purifying it essentially free of lipid A; and covalently coupling lipid A-free O-polysaccharide via at least one hydroxyl or carboxyl group of the polysaccharide to a carrier protein. Polyvalent vaccines are prepared by combining two or more monovalent vaccines for different serotypes prepared according to the present invention. The present also relates to conjugates used in the vaccines. The conjugates of the present invention are the O-polysaccharide region of an E. coli lipoplysaccharide molecule covalently coupled to a carrier protein.

Abstract: A multi-purpose resin synthesized from a mixture of a protein and a carbohydrate by ammoniation instead of hydrolysis is described. Any primary product of photosynthesis (glucose, starch or lignocellulose) is qualified for use as the carbohydrate component of the resin, which is an expedient, low-cost and benign substitute for conventional thermosetting resins in the manufacture of numerous industrial products.

Abstract: A stabilized conjugated peptide complex comprising a peptide conjugatively coupled to a polymer including lipophilic and hydrophilic moieties, wherein the peptide may for example be selected from the group consisting of insulin, calcitonin, ACTH, glucagon, somatostatin, somatotropin, somatomedin, parathyroid hormone, erythropoietin, hypothalamic releasing factors, prolactin, thyroid stimulating hormones, endorphins, enkephalins, vasopressin, non-naturally occurring opioids, superoxide dismutase, interferon, asparaginase, arginase, arginine deaminease, adenosine deaminase, ribonuclease, trypsin, chymotrypsin, and papain.

Abstract: This invention pertains to immunogenic conjugates comprising a carbohydrate containing antigen or other antigen bound to or genetically fused with a cytokine, lymphokine, hormone or growth factor having immunomodulating activity, wherein the cytokine, lymphokine, hormone or growth factor is capable of modifying immunogenicity of the carbohydrate containing antigen. The cytokine or lymphokine can be an interleukin or an interferon. The immunogenic conjugate can be used in vaccine and co-vaccine formulations.

Abstract: Pharmaceutical compositions for continuous release of a physiologically active substance in which the physiologically active substance comprises a polypeptide covalently conjugated to a water soluble polymer show particularly desirable release characteristics. Polypeptides for use in the pharmaceutical compositions include G-CSF and solution stable derivatives thereof, human calcitonin and interleukin-2. The material of the composition may be a polylactide or biodegradable hydrogel derived from an amphipathic block copolymer.The compositions enable a therapeutically effective polypeptide to be continuously released over a prolonged period of time following a single administration of the pharmaceutical composition to a patient.

Abstract: The invention relates to conjugates composed ofa) at least one polyalcohol or a derivatized polyalcohol,b) at least one active agent,c) at least one linker andd) a protein,wherein the polyalcohol(s) or the derivatized polyalcohol(s) are polyalcohols or derivatized polyalcohols which are not recognized by the defense system of an organism as exogenous, and the protein is a protein which can be taken up by the tumor specifically or non-specifically, and is not recognized by the defense system of an organism as exogenous. These conjugates are suitable for, on the one hand, making possible a very sensitive method in nuclear medicine for the diagnosis of tumors and, on the other hand, for example also offering new methods for diagnosing tumors in X-ray diagnosis, computerized tomography, nuclear spin tomography, electron spin resonance spectroscopy or electron microscopy.

Abstract: Antigens and vaccines containing purified oligomers (1-50 units) of the repeating pentasaccharide unit of type III Group B Stretococcus (III GBS) polysaccharide capsule. Methods of making the antigen by recovering polysaccharide from cultured III GBS or medium and digesting the polysaccharide with a specific endo-.beta.-galactosidase. Enzymatic cleavage of bacterial polysaccharide to make purified oligomers. A purified trypsin-resistant C surface protein, m.w. about 14,000 and vaccine. Passive immunization using the above vaccines. Immunoassays for GBS immunodeterminants or anti-GBS antibodies.

Abstract: Disclosed are blendpolymers prepared by suspending at least one protein-containing material and at least one polysaccharide-containing material in at least one solvent, by heating the suspension up to 50.degree. C. until at least 50% of the protein-containing and polysaccharide-containing materials are dissolved, then cooling the mixture down to room temperature and evaporating the solvent. These blendpolymers can be used to manufacture moulded objects, in particular, articles of daily use, preferably bio-compatible articles, such as containers, capsules, foils or films.

Abstract: A method for separating high density lipoproteins from blood serum or plasma. The method involves contacting the blood sample with an absorbant material comprising porous silica or silicate to adsorb the high density lipoprotein in preference to other lipoproteins in the blood sample. When combined with means for removing very low density lipoproteins and chylomicrons from the blood sample, the remaining low density lipoproteins can be measured directly.

Abstract: Method for the chemical modification of proteins using a reagent of general formula ##STR1## obtained from the diene ##STR2## and maleic anhydride by Diels-Alder addition.

Abstract: Disclosed are biocompatible viscoelastic gel slurries formed from a polymeric gel, preferably a hyaluronan or a derivative thereof such as hylan swollen in an aqueous medium and a fluid phase which is an aqueous solution of a polymer which may also but not necessarily be a hyaluronan or derivative thereof. Also disclosed are methods of making such slurries, controlling their rheological properties and the uses thereof.

Abstract: Methods are provided for the purification of interleukin-2 (IL-2) from a wide variety of sources, including synthetic mixtures, culture medium conditioned by natural IL-2 producing cells, and mammalian and bacterial recombinant IL-2 expression systems. The methods of the invention employ IL-2 receptor-affinity adsorbents in which soluble IL-2 receptors have been immobilized on solid supports. Through the use of these affinity adsorbents, highly purified IL-2 can be produced in a single step from bacterial extracts or conditioned medium. The IL-2 thus purified is largely free of aggregated forms, which are often present when other purification methods are used.

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 method of crosslinking protein comprises making a composition which comprises a protein, a sugar, a water-soluble salt of a carboxylic acid, water, and an additional ingredient which is to be encapsulated or entrapped within the crosslinked protein matrix. The composition is thereafter heated while maintaining the moisture content at a level of at least about 3 weight percent, based on the weight of the composition.A product comprises a protein which is crosslinked to degree at which it is substantially insoluble upon being placed in water at 100.degree. C. for at least 3 minutes, a sugar, a water-soluble salt of a carboxylic acid, water, and an additional ingredient which is encapsulated or entrapped within the crosslinked protein matrix.

Abstract: The present invention relates to an improved method for producing oligosaccharide conjugate vaccines. In an additional aspect of the invention, oligosaccharide vaccines are produced which elicit a monospecific and homogeneous immune response to capsular polysaccharide. A specific embodiment of the invention provides for vaccines which induce immunity to prevalent serotypes of Streptococcus pneumoniae.

Abstract: Methods are provided for the purification of interleukin-2 (IL-2) and chimeric proteins containing an IL-2 moiety from a wide variety of sources, including synthetic mixtures, cell culture conditioned medium and mammalian and bacterial recombinant expression systems. The methods of the invention employ IL-2 receptor-affinity adsorbents in which soluble IL-2 receptors have been immobilized on solid supports. Through the use of these affinity adsorbents, highly purified IL-2 and chimeric proteins containing an IL-2 moiety can be produced in a single step from bacterial extracts or conditioned medium. The proteins thus purified are largely free of aggregated forms, which are often present when other purification methods are used.

Abstract: Disclosed herein is an infection protectant which is excellent in infection protective effects and is also safe. .kappa.-Casein, a sialic-acid-conjugated protein derived from cow milk, and a glycomacropeptide derived from .kappa.-casein, each of which is useful as an active ingredient in this invention, have been found to be effective for the prevention of adhesion of E. coli on cells and also for the inhibition of transformation of lymphocytes by EBV and also to have strong HI activity against virus. The infection protectant of this invention is hence believed to exhibit marked effects for the prevention of occurrence of infectious diarrhea, for mass protection against spreading of influenza, and also against canceration of lymphocytes. Since the active ingredient of the infection protectant is a substance derived from cow milk, it is free of any problem from the viewpoint of safety. Moreover, it is absolutely tasteless and odorless. It can therefore be added to foods for its application.

Abstract: A method for crosslinking protein comprises making an aqueous compositiion of a protein, sugar, a salt, and water, followed by heating the composition while maintaining the moisture content of the composition at a level of at least about 3 weight percent. The composition is made, and the heating carried out, so that the protein is crosslinked to a degree at which it is substantially water insoluble upon being placed in water at 100.degree. C. for at least 3 minutes. A crosslinked protein product comprises a protein crosslinked to a degree that it is substantially water insoluble upon being placed in water at 100.degree. C. for at least 3 minutes, a sugar, a salt, and water.

Abstract: Preparation of a composite of mannan binding protein attached to an insoluble, support matrix is accomplished by reacting cyanogen bromide activated beaded agarose with a buffered solution of mannan binding protein isolated from rabbit serum. The composite has utility as an affinity sorbent for IgM when divalent metal ions are incorporated in the binding buffer. The composite does not show cross-reactivity (binding) with immunoglobulins of the G class.

Abstract: A novel hyposensitization agent was prepared by covalently attaching a saccharide to a cedar pollen allergen having a partial amino acid sequence of Ala-Ile-Asn-Ile-Phe-Asn- beginning at its N-terminal. The hyposensitization agent, when compared with an intact cedar pollen allergen, extremely accelerates 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. Thus, the hyposensitization agent is administrable to cedar pollinosis patients with no anaphylaxis and allergy, and cuts hyposensitization period to about 1/3 to 1/200.

Abstract: Homogeneous cyclophilin, a soluble binding protein, having a specific binding activity of above 50 ug cyclosporin A per mg protein and a molecular weight of about 17,600 daltons, reversibly binds immunosuppressants or antibodies thereto such as cyclosporin or anti-cyclophilin. It is isolated from the cytosol of several different mammalian tissues and can be used in various diagnostic and purifications procedures.

Abstract: The present invention provides cleavable conjugates whose linkers contain a labile bond that is cleavable under a variety of mild conditions, including weakly acidic. Since the agent may be bonded directly to the linker, cleavage can result in release of native agent. The invention also provides methods for producing cleavable conjugates. Preferred agents include drugs, toxins, biological response modifiers, radiodiagnostic compounds, radiotherapeutic compounds, and derivatives thereof. The targeting molecule employed in the invention may be an intact molecule, a fragment thereof, or a functional equivalent thereof. In a particularly preferred embodiment, the targeting molecule is a monoclonal antibody directed towards a tumor-associated antigen in man. The invention further provides methods for delivering to the cytoplasm of target cell an agent free of its targeting molecular carrier.

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: The invention relates to a new method of immunological analysis for serum amyloid A protein (SAA) and serum amyloid P-component (SAP), kits therefor and a method of purification of SAA and SAP. These methods are based on the efficient binding of SAP to a plastic surface and to carriers bearing nitrated phenyl groups in the presence of calcium and related bivalent ions, and of SAA to a plastic surface and to carriers bearing nitrated phenyl groups with or without calcium ions. The method of immunological analysis allows for rapid and reliable screening of serum samples with a high sensitivity. SAA and SAP play a key role in the diagnosis and management of inflammatory diseases.

Abstract: The invention relates to a process for producing a fucosyl antigen charcterized in that an oligosaccharide contaning an .alpha.-fucoyransoyl-(1.fwdarw.3)-, -(1.fwdarw.4)- or -(1.fwdarw.6)-galactoyransoyl group and serving as a hapten is reacted wtih a carrier protein to obtain a carbohydrate antigen and to a process for producing from the antigen an antibody having specific reactivity with cells of cancers of the digestive system, especially human colon carcinoma cells, and murine teratocarcinoma cells.The invention also relates to a method of determining a cancer associated crabohydrate linkage with use of such antibody capable of specifically recognizing specific carbohydrate linkage and to a cancer diagnosing kit containing the antibody.

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.