Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
  • A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
  • A61L29/14—Materials characterised by their function or physical properties, e.g. lubricating compositions
  • A61L29/16—Biologically active materials, e.g. therapeutic substances
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
  • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
  • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
  • A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
  • A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
  • A61K47/6803—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
  • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
  • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
  • A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
  • A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
  • A61K47/6803—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
  • A61K47/6811—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being a protein or peptide, e.g. transferrin or bleomycin
  • A61K47/6817—Toxins
  • A61K47/6819—Plant toxins
  • A61K47/6825—Ribosomal inhibitory proteins, i.e. RIP-I or RIP-II, e.g. Pap, gelonin or dianthin
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
  • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
  • A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
  • A61K47/6957—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a device or a kit, e.g. stents or microdevices
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
  • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
  • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
  • A61L27/54—Biologically active materials, e.g. therapeutic substances
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
  • A61P31/04—Antibacterial agents
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
  • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
  • A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
  • A61L2300/252—Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
  • A61L2300/254—Enzymes, proenzymes
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
  • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
  • A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
  • A61L2300/252—Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
  • A61L2300/256—Antibodies, e.g. immunoglobulins, vaccines
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
  • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
  • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
  • A61L2300/404—Biocides, antimicrobial agents, antiseptic agents

Definitions

• the invention relates to the delivery of antimicrobial toxins using antimicrobial antibodies/ ligands conjugated with the toxins.
• antibodies/ligands having affinities for microorganisms are conjugated with toxins that kill or inhibit at least some forms of microorganisms.
• the invention further relates to medical devices associated with toxin- conjugated antimicrobial antibodies/ligands.
• microorganisms can be associated with disease in animals.
• the diseases can be due to a systemic infection with microorganisms or due to proliferation of microorganisms in a localized area of the body, such as sinuses or gastrointestinal track.
• a systemic infection with microorganisms or due to proliferation of microorganisms in a localized area of the body, such as sinuses or gastrointestinal track.
• many microbial infections can be difficult to treat and remain potentially fatal.
• serious microbial infections can be associated with the invasive use of
• Medical articles are being developed that incorporate standard antibiotics on the surface of the device.
• the in vitro efficacy of these modified articles has yet to be determined.
• their use on a permanently indwelling device such as a heart valve prosthesis may be contraindicated in certain embodiments due to the increased risk of developing an antibiotic resistant infection.
• the invention pertains to an antimicrobial conjugate comprising an antibody or ligand associated with an antimicrobial agent.
• the antibody or ligand has an affinity for microbial antigens or receptors.
• the invention pertains to a medical article comprising a biocompatible material associated with an antimicrobial conjugate.
• the antimicrobial conjugate comprises an antibody or ligand bonded to an antimicrobial agent.
• the antibody or ligand has an affinity for microbial antigens or receptors .
• the invention pertains to a method of eliminating viable microorganisms comprising placing an antimicrobial conjugate in contact with a solution from which viable microorganisms are to be eliminated.
• the antimicrobial conjugate preferably comprises an antibody or ligand associated with an antimicrobial agent.
• the antibody or ligand has an affinity for microbial antigens or receptors.
• the toxin is brought into physical proximity with a microorganism.
• the microbial cell that attaches to the antibody/ligand becomes the target of the toxin associated with the antibody/ligand. Since the antibodies/ligands direct the toxin to a microorganism, any potential toxicity to the patient's cells is reduced or eliminated. Furthermore, due to synergism resulting from targeting with the antibody/ ligand, the effectiveness of the toxin against the microorganisms should increase significantly for a particular amount of toxin.
• the toxins are conjugated to an antibody or ligand, either natural or synthetic, to direct the toxin to target microorganisms .
• the term antibody is intended for broad interpretation as any type of immunoglobulin, modified immunoglobulins and/or fragments thereof.
• the specific binding portion of an appropriate antibody recognizes a cell surface feature, generally a cell surface antigen, of target microorganisms.
• the term ligand is intended for broad interpretation ' as any specific binding agent, other than an antibody, that has specificity for a cell receptor, generally a cell surface receptor.
• Bacterial adhesins can be divided into two major groups: pili or fimbriae adhesins and non-pilus or afimbrial adhesins.
• pili or fimbriae adhesins and non-pilus or afimbrial adhesins.
• a single pathogen may express many different adhesins, and some of these organisms have a highly evolved capacity for genetic rearrangement that allows for antigenic variation.
• RIP immunotoxin as an antimicrobial toxin.
• these are very potent toxins with an enzymatic nechanism and IC 50 (concentration to achieve 50 percent protein synthesis inhibition) values in the nanomolar range .
• IC 50 values for ricin A-chain activity is described by Press et a1. , Immunol. Letters, 14:37-41 (1986), incorporated herein by reference. Only low levels of antibody/ligand binding are needed to produce toxicity. The implication is that antibodies/ligands binding even minor components of the bacterial cell surface can be used as targets. This increases the likelihood of finding appropriate cross- strain antigens for broad spectrum toxicity.
• the medical article can be constructed such that the additional antimicrobial agents are associated with only a particular region of the medical article, such as at different portions of a biocompatible material or in different biocompatible materials of the medical device.
• a region of the medical article is not associated with toxin-conjugated antibodies/ligands, that region can be associated with an alternative antimicrobial agent to reduce the risk of infection.
• the toxin conjugated antibodies/ligands preferably are formulated into a pharmaceutical composition for packaging and distribution.
• the packages generally include instructions for administration of the composition and other labels including labels required by the Food and Drug Administration.
• the toxin-conjugated antibodies/ligands can be formulated into injectable preparations, preparations for oral administration and/or topical preparations.
• Preferred injectable formulations include therapeutically effective amounts of toxin-conjugated antibodies/ligands in a sterile liquid solution or a sterile liquid suspension, particularly a glycerol suspension. Lyophilized versions of the formulations can be prepared, which are reconstituted later with injectable liquid carriers, such as sterile water, saline, or 0.3% glycine.
• a solution of the toxin- conjugated antibody/ligand is packaged separately from the medical article along with instructions for performing modification of a medical article and, optionally, distributed together as a kit.
• a kit can be distributed comprising a container of the toxin-conjugated antibody/ligand and a separate container of a chemical binding agent or an adhesive, optionally along with instructions for modification of a biocompatible material.
• a selected medical device can be modified using the compositions from the kit prior to medical use. Once the medical device is modified with the toxin-conjugated antibody/ligand, it can be implanted/applied or stored for a reasonable period of time .
• incorpora toxin-conjugated antibody/ ligand into a medical device can reduce the risk of infection associated with the contact of the medical article with the patient's bodily fluids or tissue. Reduction in the risk of infection thereby reduces associated health risks to the patient from microbial infections associated with implantation of the medical article. By reducing the risk of infection, there is a corresponding reduction in the need for replacement of the medical article.
• the toxin-conjugated antibodies/ligands are particularly effective for the treatment of microorganisms that are resistant and infections, such as biofilms, which are difficult to treat. Furthermore, the toxin-conjugated antibodies/ligands are more easily able to target specific microorganisms.

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• Health & Medical Sciences (AREA)
• Engineering & Computer Science (AREA)
• Life Sciences & Earth Sciences (AREA)
• Bioinformatics & Cheminformatics (AREA)
• Chemical & Material Sciences (AREA)
• Medicinal Chemistry (AREA)
• General Health & Medical Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• Public Health (AREA)
• Veterinary Medicine (AREA)
• Epidemiology (AREA)
• Pharmacology & Pharmacy (AREA)
• Molecular Biology (AREA)
• Immunology (AREA)
• Biomedical Technology (AREA)
• Toxicology (AREA)
• Oral & Maxillofacial Surgery (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• Transplantation (AREA)
• Dermatology (AREA)
• Heart & Thoracic Surgery (AREA)
• Communicable Diseases (AREA)
• Oncology (AREA)
• Chemical Kinetics & Catalysis (AREA)
• General Chemical & Material Sciences (AREA)
• Botany (AREA)
• Organic Chemistry (AREA)
• Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Peptides Or Proteins (AREA)
• Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
• Medicinal Preparation (AREA)
• Materials For Medical Uses (AREA)

Priority Applications (3)

Applications Claiming Priority (2)

Publications (2)

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Family Applications (1)

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Cited By (6)

Families Citing this family (1)

• 2000
  • 2000-03-30 BR BR0009947-3A patent/BR0009947A/pt not_active Application Discontinuation
  • 2000-03-30 WO PCT/US2000/008389 patent/WO2000064487A2/en not_active Ceased
  • 2000-03-30 EP EP00921508A patent/EP1212094A2/en not_active Withdrawn
  • 2000-03-30 JP JP2000613477A patent/JP2003523315A/ja active Pending
• 2001
  • 2001-10-19 ZA ZA200108639A patent/ZA200108639B/en unknown

Non-Patent Citations (1)

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