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WO1994025061A1 - Procedes et compositions permettant de traiter des maladies au moyen d'enzymes de modification d'hydrates de carbone - Google Patents

Procedes et compositions permettant de traiter des maladies au moyen d'enzymes de modification d'hydrates de carbone Download PDF

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Publication number
WO1994025061A1
WO1994025061A1 PCT/US1994/004464 US9404464W WO9425061A1 WO 1994025061 A1 WO1994025061 A1 WO 1994025061A1 US 9404464 W US9404464 W US 9404464W WO 9425061 A1 WO9425061 A1 WO 9425061A1
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WIPO (PCT)
Prior art keywords
diseases
carbohydrate
binding pair
enzyme
therapeutic
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Ceased
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PCT/US1994/004464
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English (en)
Inventor
John C. Klock, Jr.
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Glyko Inc
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Glyko Inc
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Publication of WO1994025061A1 publication Critical patent/WO1994025061A1/fr
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Ceased legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y302/00—Hydrolases acting on glycosyl compounds, i.e. glycosylases (3.2)
    • C12Y302/01—Glycosidases, i.e. enzymes hydrolysing O- and S-glycosyl compounds (3.2.1)
    • C12Y302/01051—Alpha-L-fucosidase (3.2.1.51)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43—Enzymes; Proenzymes; Derivatives thereof
    • A61K38/46—Hydrolases (3)
    • A61K38/465—Hydrolases (3) acting on ester bonds (3.1), e.g. lipases, ribonucleases
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43—Enzymes; Proenzymes; Derivatives thereof
    • A61K38/52—Isomerases (5)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14—Hydrolases (3)
    • C12N9/24—Hydrolases (3) acting on glycosyl compounds (3.2)
    • C12N9/2402—Hydrolases (3) acting on glycosyl compounds (3.2) hydrolysing O- and S- glycosyl compounds (3.2.1)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y302/00—Hydrolases acting on glycosyl compounds, i.e. glycosylases (3.2)
    • C12Y302/01—Glycosidases, i.e. enzymes hydrolysing O- and S-glycosyl compounds (3.2.1)
    • C12Y302/01018—Exo-alpha-sialidase (3.2.1.18), i.e. trans-sialidase
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

Definitions

  • the subject invention is in the field of medical therapeutics, in particular, the field of therapies aimed at altering the carbohydrate structures naturally in the body.
  • Carbohydrates play a number of extremely important roles in living organisms. In addition to their roles as metabolic fuels and energy storage materials, carbohydrates may serve as binding and recognition signals. Carbohydrates may exist as free molecules in the body or carbohydrates may be covalently attached to numerous other molecules such as proteins (glycoproteins) and lipids (glycolipids) . Molecules such as glycoproteins and glycolipids are generally referred to as glycoconjugates. The carbohydrate portions of glycoconjugates may comprise up to 5-10% of the dry weight of a living cell, tissue or organ in the body.
  • carbohydrate-splitting i.e., hydrolysis, actions
  • carbohydrate-buildup actions some have the ability to chemically "shield", "coat”, or cover the surface of a carbohydrate to mask ' or modify its biologic activity.
  • This array of carbohydrate-modifying enzymes also has the ability to modify or correct the chemical structure of the body's carbohydrates so as to prevent disease or to counteract diseases once they are established.
  • glycoconjugates The biological importance of the carbohydrate portion of glycoconjugates is apparent because the "protein" portion of a glycoprotein will not function optimally without its carbohydrate part.
  • Biologically important molecules that are glycoproteins include enzymes, growth factors, hormones, antibodies, and the like. Because of the diverse and important biological functions of carbohydrates, aberrations in carbohydrate synthesis, degradation, or structure may give rise to disease. Such diseases may be caused by changes in carbohydrates as a result of infections, cancer, environmental factors, chemicals or metabolic imbalance in the body's own physiological systems. Many diseases are described that are associated with changes in carbohydrate structure and abundance. These diseases include cancer and leukemia (Fukuda, M.
  • human inflammatory disease may be treated by biologically "disabling" the white blood cell homing system.
  • the disabling of these white blood cells causing inflammation may be accomplished using a naturally-occurring carbohydrate-splitting enzyme applied in a therapeutic manner to patients with overactive white blood cells.
  • the active carbohydrate on white blood cells is a structure called "sialyl Lewis-x" which has two important sugars, fucose and sialic acid. Removal of either of these sugars or otherwise blocking their contact with other molecules will disable the inflammatory response.
  • Such removal of sugars is normally accomplished in the body by two enzymes: one which removes the fucose called ⁇ -L-fucosidase and one which removed the sialic acid called ⁇ -sialidase.
  • ⁇ -L-fucosidase Such a strategy for disabling white blood cells using purified ⁇ -L-fucosidase and ⁇ -sialidase could be used as a treatment for patients with burns of the skin, various skin diseases, arthritis, lung disease, or any number of other medical conditions.
  • the subject invention provides methods of * treating or preventing various disease conditions by interfering with a carbohydrate mediated interaction between two members of a receptor binding pair.
  • the interaction between the members of a receptor binding pair are disrupted by modifying either one or both of the binding pair members by means of a chemical reaction catalyzed by a therapeutic catalyst.
  • a therapeutic catalyst is typically an enzyme capable of catalyzing a reaction that adds carbohydrates to, removes carbohydrates from, or modifies the structure of carbohydrates already present, on a member of a receptor binding pair that may be involved in mediating a disease condition.
  • the therapeutic catalyst may be administered to a subject in a variety of ways.
  • An aspect of the subject invention is to provide for compositions for use in the subject methods, where the compositions are formulated so as to be adapted to the specific method of administration.
  • One aspect of the subject invention is to provide for the administration of the therapeutic catalyst by parenteral administration.
  • Another aspect of the subject invention is to provide for the administration of therapeutic catalysts by producing cellular transformation vectors containing nucleic acid sequences encoding therapeutic catalysts that are carbohydrate-modifying enzymes.
  • receptor binding pair refers to a set of two molecules having a specific, i.e. v , non-random, binding affinity for one another.
  • specific binding pairs include antibodies and antigens, cell surface receptors and ligands, and the like. At least one member of a receptor binding pair may be immobilized to the surface of a cell. Additionally, both members of a receptor binding pair maybe cell surface molecules, so as to provide for specific cell-cell interactions.
  • the individual molecules forming a receptor binding pair may be proteins, nucleic acids, carbohydrates, or small organic molecules. Individual components of a receptor binding pair also may be multi-subunit proteins.
  • carbohydrate mediated interaction refers to a specific, i.e. non-random, physical interaction between molecules forming a receptor binding pair in which at least a portion of one of the molecules contacting the other molecule is a carbohydrate.
  • carbohydrate mediated interaction between receptor binding pair members.
  • carbohydrate mediated interaction between receptor binding pair members.
  • the interaction between receptor binding pair members may be carbohydrate-mediated interactions.
  • therapeutic catalyst refers to catalysts used for administration to a patient.
  • Therapeutic catalysts may be enzymes, polynucleic acid sequences (including ribozymes) , and the like.
  • the term "therapeutic catalyst” as used herein refers to carbohydrate modifying enzymes and other molecules capable of catalyzing a reaction catalyzed by a carbohydrate modifying enzyme.
  • the therapeutic catalysts of the subject invention catalyze chemical reactions that may be catalyzed by carbohydrate-modifying enzymes.
  • a substrate of a therapeutic catalyst is a member of a receptor binding pair.
  • the therapeutic catalyst catalyzes a reaction in which a carbohydrate (including the carbohydrate portion of a glycoconjugate) is structurally modified.
  • treating when used with respect a disease refers to either the treatment of the disease or the prevention of the disease.
  • carbohydrate-modifying enzyme refers to enzymes that catalyze a reaction that may alter the structure of a carbohydrate substrate in a variety of ways including the hydrolysis of linkages between monosaccharide units, the formation of linkages between monosaccharide units, the addition of various side groups to carbohydrate molecules, and the structural alteration of a carbohydrate molecule without the addition or removal of any atoms.
  • Classes of carbohydrate-modifying enzymes include hydrolases, lyases, acetylase, sulfatases, phosphatases, kinases, epimerases, methylases, amidases, transaminases, and oxioreductases.
  • Carbohydrate modifying enzymes may also be identified by reference to the nomenclature system recommended by the International Union of Biochemistry; carbohydrate modifying enzymes include enzymes in classes 1.1-1.17, and various subclasses thereof, 2.1-2.8 and various subclasses thereof, 3.1-3.11 and various subclasses thereof, 4.1-4.99 and various subclasses thereof, 5.1-5.99 and various subclasses thereof, and 6.1-6.5 and various subclasses thereof.
  • carbohydrate modifying enzymes include ⁇ -L-fucosidase, ⁇ -sialidase (neuraminidase) , ⁇ - galactosidase, ⁇ -galactosidase, o.-mannosidase, ⁇ - mannosidase, ⁇ -iduronidase, hexosyl sulfatase, hexosyl phosphastase, hexosylacetylase, ⁇ - xylosidase, and hexosyl epimerase.
  • the subject invention provides novel methods and compositions for treating a variety of diseases in humans and other mammals by administering therapeutic catalyst, i.e., enzymes or similar catalysts, capable of catalyzing chemical reactions in which the structure of a receptor binding pair member (or members) is altered by the addition, removal, or other structural alteration of carbohydrate components of a receptor binding pair member.
  • therapeutic catalyst i.e., enzymes or similar catalysts
  • Disruption of carbohydrate-mediated receptor binding pair interactions may have various beneficial effects, depending upon the choice of which receptor binding pair interaction is to be disrupted.
  • the subject invention differs substantially from many other forms of medical therapy in which an enzyme (or similar catalyst) is added to the body either directly or through genetic therapy methods because conventional therapy methods involve replacement of abnormally low levels of an enzyme normally present in the body.
  • the subject invention adds catalysts to the ' body so as to catalyze a chemical reaction in which the structure of a molecule is altered, whereby the biological function of the target molecule, i.e., a member of a receptor-binding pair, is destroyed, substantially reduced, or modified.
  • the subject invention provides for the treatment of diseases not necessarily caused by a deficiency of an enzyme.
  • the subject invention also provides for methods of treating infectious disease by interfering with receptor binding pair interactions.
  • Many infectious diseases involve the interaction of surface carbohydrates (or glycoconjugates) present on a microorganism (or multicellular parasite) with receptors (carbohydrate or otherwise) present in a host.
  • many infectious diseases involve the interaction of receptors (carbohydrate or otherwise) present on a microorganism (or multicellular parasite) with carbohydrates (or glycoconjugates) present on cells in a host.
  • These receptor binding pair interactions between a host and an infectious organism may play important roles in the inception and/or progression of various infectious diseases.
  • Interference with the interaction of receptor binding pair members, where one of the binding pair members is present on a infectious organism may be achieved by administering a therapeutic catalyst so as to catalyze a chemical reaction that modifies a binding pair member so as to interfere with the interaction between binding pair members.
  • Some infectious organisms possess surface carbohydrates or glycoconjugates that serve to promote the infection process by providing a mechanism for evading the hosts immune system, e.g., the immunosuppressive methylated rhamnose containing glycolipid coat of Mycobacterium leprae. It is also of interest to provide therapeutic catalysts capable of catalyzing chemical reactions that modify the structure of these immune system evading carbohydrates so as to provide for their recognition by a host's immune system.
  • Carbohydrate structures may be determined empirically or by review of the literature. A particularly useful compilation of carbohydrate structures can be found in the CarbBank Complex Carbohydrate Structure Database that may be obtained from the University of
  • Suitable therapeutic catalysts are selected on the basis of their ability to catalyze chemical reactions capable of structurally modifying the receptor binding pair member of interest. Numerous enzymes and other catalysts have previously been identified; by reviewing the available scientific literature, catalysts capable of using the receptor binding pair member of interest may be selected. Additionally, catalysts capable of catalyzing reactions modifying specific carbohydrate structures may be found using the-methods described in U.S. patent application 07/840,739, filed February 25, 1992 and entitled "Fluorophore-Assisted Cloning Analysis" which is herein incorporated by reference.
  • compositions containing therapeutic catalysts may be administered in a number of different ways including, topically, orally, intranasally, by injection or by inhalation in the form of a pharmaceutical compositions comprising a therapeutic catalyst in the form of the original compound or optionally in the form of a pharmaceutically acceptable salt thereof, in association with a pharmaceutically acceptable carrier which may be a solid, semi-solid or liquid diluent or an ingestible capsule, and such compositions comprise a further aspect of the invention.
  • the therapeutic catalysts may also be used with carrier material.
  • the therapeutic catalyst containing pharmaceutical compositions of the invention may be formulated so as to be adapted for different sites of administration to a subject.
  • compositions include tablets, drops such as nasal drops, compositions for topical application such as ointments, jellies, creams and suspensions, aerosols for inhalation, nasal spray, liposomes, etc.
  • the therapeutic catalyst will comprise between 0.05 and 99%, or between 0.1 and 99% by weight of the composition, for example between 0.5 and 20% for compositions intended for injection and between 0.1 and 50% for compositions intended for oral administration.
  • therapeutic catalysts When therapeutic catalysts are administered in the form of a subcutaneous implant, the compound is suspended or dissolved in a slowly dispersed material known to those skilled in the art, or administered in a device which slowly releases the active material through the use of a constant driving force such as an osmotic pump. In such cases administration over an extended period of time is possible.
  • the catalyst may be mixed with a solid, pulverulent carrier, for example lactose, saccharose, sorbitol, mannitol, a starch such as potato starch, corn starch, amylopectin, laminaria powder or citrus pulp powder, a cellulose derivative or gelatine and also may include lubricants such as magnesium or calcium stearate or a Carbowax ® or other polyethylene glycol waxes nd compressed to form tablets or cores for dragees.
  • a solid, pulverulent carrier for example lactose, saccharose, sorbitol, mannitol, a starch such as potato starch, corn starch, amylopectin, laminaria powder or citrus pulp powder, a cellulose derivative or gelatine and also may include lubricants such as magnesium or calcium stearate or a Carbowax ® or other polyethylene glycol waxes nd compressed to form tablets or cores for dragees.
  • the cores may be coated for example with concentrated sugar solutions which may contain gum arabic, talc and/or titanium dioxide, or alternatively with a film forming agent dissolved in easily volatile organic solvents or mixtures of organic solvents.
  • Dyestuffs can be added to these coatings, for example, to distinguish between different contents of active substance.
  • the active substance may be admixed with a Carbowax ® or a suitable oil as e.g. sesame oil, olive oil, or arachis oil.
  • Hard gelatine capsules may contain granulates of the active substance with solid, pulverulent carriers such as lactose, saccharose, sorbitol, mannitol, starches (for example) potato starch, corn starch or amylopectin) , cellulose derivatives or gelatine, and may also include magnesium stearate or stearic acid as lubricants.
  • solid, pulverulent carriers such as lactose, saccharose, sorbitol, mannitol, starches (for example) potato starch, corn starch or amylopectin) , cellulose derivatives or gelatine, and may also include magnesium stearate or stearic acid as lubricants.
  • Therapeutic catalysts of the subject invention may also be administered parenterally such as by subcutaneous, intramuscular or intravenous injection or by sustained release subcutaneous implant.
  • the therapeutic catalyst (the active ingredient) may be dissolved or dispersed in a liquid carrier vehicle.
  • the active material may be suitably admixed with an acceptable vehicle, preferably of the vegetable oil variety such as peanut oil, cottonseed oil and the like.
  • an acceptable vehicle preferably of the vegetable oil variety such as peanut oil, cottonseed oil and the like.
  • Other parenteral vehicles such as organic compositions using solketal, glycerol, formal, and aqueous parenteral formulations may also be used.
  • compositions may comprise an aqueous solution of a water soluble pharmaceutically acceptable salt of the active acids according to the invention, desirably in a concentration of 0.5 - 10%, and optionally also a stabilizing agent and/or buffer substances in aqueous solution. Dosage units of the solution may advantageously be enclosed in ampoules.
  • the pharmaceutical compositions are suitably in the form of an ointment, gel, suspension, cream or the like. The amount of active substance may vary, for example between 0.05-20% by weight of the active substance.
  • Such pharmaceutical compositions for topical application may be prepared in known manner by mixing the active substance with known carrier materials such as isopropanol, glycerol, paraffin, stearyl alcohol, polyethylene glycol, etc.
  • the pharmaceutically acceptable carrier may also include a known chemical absorption promoter.
  • absorption promoters are, e.g., dimethylacetamide (U.S. Pat. No. 3,472,931), trichloro-ethanol or trifluoroethanol (U.S. Pat. No. 3,891,757), certain alcohols and mixtures thereof (British Pat. No. 1,001,949).
  • a carrier material for topical application to unbroken skin is also described in the British patent specification No.
  • 1,464,975 which discloses a carrier material consisting of a solvent comprising 40-70% (v/v) isopropanol and 0-60% (v/v) glycerol, the balance, if any, being an inert constituent of a diluent not exceeding 40% of the total volume of solvent.
  • the dosage at which the therapeutic catalyst containing pharmaceutical compositions are administered may vary within a wide range and will depend on various factors such as for example the severity of the infection, the age of the patient, etc., and may have to be individually adjusted.
  • As a possible range for the amount of therapeutic catalyst which may be administered per day be mentioned from about 0.1 mg to about 2000 mg or from about 1 mg to about 2000 mg.
  • Th pharmaceutical compositions containing the therapeutic catalysts may suitably be formulated so that they provide doses within these ranges either as single dosage units or as multiple dosage units.
  • a therapeutic catalyst may be formulated so that they provide doses within these ranges either as single dosage units or as multiple dosage units.
  • the subject formulations may contain one or more substrates or cofactors for the reaction catalyzed by the therapeutic catalyst in the'compositions.
  • Therapeutic catalyst containing compositions may also contain more than one therapeutic catalyst.
  • the therapeutic catalysts employed in the subject methods and compositions may also be administered by means of transforming patient cells with polynucleic acids encoding the therapeutic catalyst when the therapeutic catalyst is a protein or ribonucleic acid sequence.
  • the therapeutic catalyst encoding sequence may be incorporated into a vector for transformation into cells of the subject to be treated.
  • the vector may be designed so as to integrate into the chromosomes of the subject, e.g., retroviral vectors, or to replicate autonomously in the host cells.
  • Vectors containing therapeutic catalyst encoding nucleotide sequences may be designed so as to provide for continuous or regulated expression of the therapeutic catalysts.
  • the genetic vector encoding the therapeutic catalysts may be designed so as to stably integrate into the cell genome or to only be present transiently.
  • the Human ⁇ -fucosidase gene was cloned form Human liver poly-A RNA by Reverse Transcriptase- Polymerase Chain Reaction (RT-PCR) techniques. Two sets of PCR primers were designed by inspection of the published sequence (Fu ushima H et al, Proc. Natl. Acad. Sci. USA. 82:1262-1265, 1985) of Human liver ⁇ -fucosidase. The first set (5' set) consisted of the following sequences: 5 1 Forward (5'
  • the 5 1 and 3' sets of primers were added to their respective cDNA reactions and PCR was performed with the following protocol:
  • the DNA from the 5 1 set of primers (5* DNA) was cleaved with restriction enzymes Xbal and ApaLl.
  • Sialidase (Neuraminidase) from Clostridium perfringens was cloned by PCR directly from Clostridium DNA. By inspection of the DNA sequence of Clostridium sialidase gene (Roggentin P et al, FEBS Letters 238:31-34, 1988), the following primers were designed: Forward (5*
  • sialidase gene was amplified by the following protocol:
  • the DNA was cleaved with Xbal and BamHl and ligated into plasmid pT7-3 and electroporated into strain BL21 (DE3) .
  • the colonies were screened for active sialidase activity using methylumbelliferyl-sialic acid. Positive clones were chosen.
  • the isolated human neuraminidase and fucosidase genes are used to produce neuraminidase and fucosidase, respectively, from genetically engineered host cells.
  • Neuraminidase and fucosidase were used to destroy, i.e., structurally modify, sialyl-Lewis x molecule.
  • Fucosidase and neuraminidase separately, and in combination with one another, were incubated with sialyl-Lewis x. The structural modification of the sialyl-Lewis by the enzymes was monitored, by fluorophore-assisted carbohydrate electrophoresis.
  • a galactose at the non-reducing terminus of 0- 1inked oligosaccharides in mouse egg zona pellucida glycoprotein ZP3 is essential for the sperm receptor activity of the ZP3 glycoprotein, see Wassarman, P.M., Proc. Natl. Acad. Sci. USA 85: 6778-6782 (1988) .
  • An enzyme capable of hydrolyzing the galactose at the non-reducing end of the ZP3 glycoprotein is administered to mammals in the form of a slow-release intra-vaginal suppository. The reaction catalyzed by the enzyme prevents the productive interaction between sperm and egg, thereby reducing fertility.
  • Human tumor cells are known to produce a variety of gangliosides, e.g. G ⁇ and Gr ⁇ , that are present in high concentrations and have an immunosuppressive effect on the cell surface, for example see Ladisch ££.21., PiQchJimi ⁇ a g. Bj,pph ⁇ gjca Acta 1125: 180-188 (1992), Grayson and Ladisch, Cellular Immunology 139: 18-29 (1992) .
  • a neuroblastoma is treated by injecting GQ and Gr ⁇ sialidases into a patient.
  • Neuroblastoma patients are also treated by placement of a controlled release implant containing G ⁇ and G ⁇ specific sialidases at the site of the tumor. The reaction catalyzed by the sialidase(s) alter the structure of the gangliosides so as to provide for enhanced recognition of the tumor cells by the immune system.
  • Heparin has been shown to potentiate the growth stimulatory effects of acidic fibroblast growth factor, see Gospodarawicz, P. and Cheng J. , J. Cell. Physiol. 128: 475-484.
  • the degree of sulfation of heparin and the length of the heparin chains has been shown to be important for the productive interaction between heparin and acidic fibroblast growth factor, see-Sudhalter e_£. al. , J. Bio. Chem.264: 6892-6897 (1989) .
  • the growth stimulatory effects of fibroblast growth factor can lead to the generation of scar tissue from both accidents and surgery, as well as other forms of trauma to the skin.
  • the formation of scar tissue is reduced by topically applying an ointment containing a sulfatase to the site of plastic surgery.
  • the sulfatase containing ointment is applied repeatedly so as to ensure that a high percentage of non-denatured enzyme is present at any given time.
  • Mvcobacterium tuberculae the etioloqical agent of tuberculosis possesses the same immunosuppressive glycolipid. Removal of the 0- methyl from the rhamnose constituent of the phenolic glycolipid has been shown to abolish the immunosuppressive effect. (Brennan) [Same Ref. as Hunter??]
  • a patient suffering form leprosy or tuberculosis is intravenously administered a solution containing the-enzyme rhamnose methylase, which clears the methyl-rhamnose moiety from the immunosuppressive glycolipid on the infectious organism. Side effects are minimal because of the absence of methyl- rhamnose in human cells.
  • the treatment is supplemented by administration of antibiotics known to be effective for the treatment of tuberculosis or leprosy, accordingly.
  • a patient suffering from internal bleeding caused by an excessive level of heparin is treated by intravenous administration of an iduronrate sulfatase solution.
  • the sulfatase acts as a therapeutic catalyst, catalyzing a reaction that structurally modifies heparin so as to lower its biological activity, thereby promoting clotting and reducing internal bleeding.
  • MOLECULE TYPE DNA (genomic)
  • MOLECULE TYPE DNA (genomic)
  • MOLECULE TYPE DNA (genomic)
  • MOLECULE TYPE DNA (genomic)
  • MOLECULE TYPE DNA (genomic)
  • MOLECULE TYPE DNA (genomic)

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Abstract

Cette invention a pour objet des procédés et des compositions destinés au traitement ou à la prévention d'une variété d'états pathologiques. Ces procédés consistent à administrer une dose efficace d'un catalyseur thérapeutique à un patient. Ce catalyseur thérapeutique est une enzyme ou autre, susceptible de catalyser une réaction chimique dans laquelle un hydrate de carbone ou une partie hydrate de carbone d'un glycoconjugué est utilisé comme substrat. Les catalyseurs thérapeutiques sont choisis de façon à catalyser une réaction entraînant une altération de la structure d'au moins un élément d'une paire de molécules de liaison de récepteur, l'interaction entre les éléments de cette paire étant rompue. L'invention se rapporte également à des compositions contenant des catalyseurs thérapeutiques utilisés selon les procédés décrits. Les maladies pouvant être traitées par ces catalyseurs thérapeutiques comprennent les maladies infectieuses, le cancer et les maladies auto-immunes.
PCT/US1994/004464 1993-04-23 1994-04-22 Procedes et compositions permettant de traiter des maladies au moyen d'enzymes de modification d'hydrates de carbone Ceased WO1994025061A1 (fr)

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU718184B2 (en) * 1995-07-05 2000-04-06 Cambridge University Technical Services Limited Recombinant protein having bacteriophage endosialidase enzymatic activity
WO2000063351A3 (fr) * 1999-04-21 2001-08-09 Incyte Genomics Inc Enzymes modifiant les hydrates de carbone
WO2017040499A1 (fr) * 2015-09-02 2017-03-09 Dupont Nutrition Biosciences Aps Glycoside hydrolases et leur utilisation dans la prévention et/ou le traitement d'une infection pathogène chez un animal

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1994001137A1 (fr) * 1992-07-06 1994-01-20 Hybritech Incorporated Procede d'aministration d'agents cytotoxiques et constituants de ceux-ci

Patent Citations (1)

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Publication number Priority date Publication date Assignee Title
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AU718184B2 (en) * 1995-07-05 2000-04-06 Cambridge University Technical Services Limited Recombinant protein having bacteriophage endosialidase enzymatic activity
WO2000063351A3 (fr) * 1999-04-21 2001-08-09 Incyte Genomics Inc Enzymes modifiant les hydrates de carbone
WO2017040499A1 (fr) * 2015-09-02 2017-03-09 Dupont Nutrition Biosciences Aps Glycoside hydrolases et leur utilisation dans la prévention et/ou le traitement d'une infection pathogène chez un animal
KR20180043365A (ko) * 2015-09-02 2018-04-27 듀폰 뉴트리션 바이오사이언시즈 에이피에스 글리코시드 하이돌라제 및 동물에서의 병원성 감염의 예방 및/또는 치료에서 이의 용도
CN108348585A (zh) * 2015-09-02 2018-07-31 杜邦营养生物科学有限公司 糖苷水解酶及其在预防和/或治疗动物中的病原体感染中的用途
RU2720243C2 (ru) * 2015-09-02 2020-04-28 ДюПон НЬЮТРИШН БАЙОСАЙЕНСИЗ АпС Глюкозидгидролазы и их применение в предупреждении и/или лечении патогенной инфекции у животного
EP3711773A1 (fr) * 2015-09-02 2020-09-23 DuPont Nutrition Biosciences ApS Glycoside hydrolases et leur utilisation dans la prévention et/ou le traitement d'une infection pathogène chez un animal
US10933121B2 (en) 2015-09-02 2021-03-02 Dupont Nutrition Biosciences Aps Glycoside hydrolases and their use in preventing and/or treating a pathogenic infection in an animal
US20210236606A1 (en) * 2015-09-02 2021-08-05 Dupont Nutrition Biosciences Aps Glycoside hydolases and their use in preventing and/or treating a pathogenic infection in an animal
CN108348585B (zh) * 2015-09-02 2023-12-15 杜邦营养生物科学有限公司 糖苷水解酶及其在预防和/或治疗动物中的病原体感染中的用途
KR102711565B1 (ko) * 2015-09-02 2024-09-27 인터내셔널 엔＆에이치 덴마크 에이피에스 글리코시드 하이돌라제 및 동물에서의 병원성 감염의 예방 및/또는 치료에서 이의 용도

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