EP1313506A1 - Methode immunologique pour la prevention des caries dentaires - Google Patents

Methode immunologique pour la prevention des caries dentaires

Info

Publication number
EP1313506A1
EP1313506A1 EP00959362A EP00959362A EP1313506A1 EP 1313506 A1 EP1313506 A1 EP 1313506A1 EP 00959362 A EP00959362 A EP 00959362A EP 00959362 A EP00959362 A EP 00959362A EP 1313506 A1 EP1313506 A1 EP 1313506A1
Authority
EP
European Patent Office
Prior art keywords
mutans
monoclonal antibodies
plants
human
heavy
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP00959362A
Other languages
German (de)
English (en)
Inventor
Wenyuan Shi
Maxwell H. Anderson
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Washington Dental Service
University of California
Original Assignee
Washington Dental Service
University of California
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Washington Dental Service, University of California filed Critical Washington Dental Service
Publication of EP1313506A1 publication Critical patent/EP1313506A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9783—Angiosperms [Magnoliophyta]
    • A61K8/9789—Magnoliopsida [dicotyledons]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
    • 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
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/12—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria
    • C07K16/1267—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria from Gram-positive bacteria
    • C07K16/1275—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria from Gram-positive bacteria from Streptococcus (G)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/80—Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
    • A61K2800/86—Products or compounds obtained by genetic engineering
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered

Definitions

  • This application relates to an immunologic methodology for the -. treatment and prevention of dental caries.
  • This invention has special application to patients who are without the ability or motivation to apply established principles of self care, such as very young children, the infirm and poorly educated populations.
  • Dental caries teeth decay
  • periodontal disease are probably the most common chronic diseases in the world.
  • the occurrence of cavities in teeth is the result of bacterial infection.
  • the occurrence of dental caries is
  • Streptococcus mutans is believed to be the principal cause of tooth decay in man. When S. mutans occurs in large numbers in dental plaque, and metabolizes complex sugars, the resulting organic acids cause
  • antimicrobial agents are not selective for cariogenic organisms.
  • Administration of non-specific bacteriocidal agents disturbs the balance of organisms that normally inhabit the oral cavity, with consequences that cannot be predicted, but may include creation of an environment that provides opportunities for pathogenic organisms.
  • long term use of antimicrobial agents is known to select for organisms that are resistant to them. Hence long term and population-wide use of antimicrobial agents to prevent tooth decay is not practical.
  • One drawback of this approach is that vaccination elicits production of predominantly IgG and IgM antibodies, but they are not secreted into saliva. The majority of antibodies present in saliva are of the IgA isotype, which can bind to, but cannot activate lymphocytes or complement components to kill bacteria. Accordingly, vaccination is not believed likely to be capable of producing antibodies that can trigger the immune system to kill cariogenic organisms in the mouth.
  • IgA is a multivalent antibody
  • a single molecule of IgA can bind to several different antigenic sites, resulting in clumping of bacteria.
  • binding of IgA to bacterial surface antigens does not kill the bacteria. Rather, clumping is believed to hinder the ability of bacteria to bind to tooth surfaces.
  • Another drawback of this approach is that repeated administration of mouse (i.e., heterologous) antibodies to humans has the potential to evoke an immune response to the antibodies.
  • antibodies of the IgG and IgM classes have bacteriocidal effects. Binding of IgM or IgG antibodies to antigens present on the surface of cariogenic organisms may result in the destruction of the bacterial cells by two separate mechanisms: complement mediated cell lysis and antibody- dependent cell-mediated cytotoxicity. In either case, antibodies that selectively bin to certain microbial organisms target just those cells for destruction by the immune system. Both complement mediated cell lysis and antibody-dependent cell mediated cytotoxicity are part of the humoral immune response that is mediated by antibodies of the IgG and IgM classes.
  • Dental caries may be prevented or treated by oral ingestion of human or humanized mouse monoclonal IgG and IgM antibodies that to bind surface antigens of cariogenic organisms, such as S. mutans.
  • the genetically engineered monoclonal antibodies engage the effector apparatus of the human immune system when they bind to cariogenic organisms, resulting in their destruction.
  • monoclonal antibodies to cariogenic organisms are produced by edible plants, including fruits and vegetables, transformed by DNA sequences that code on expression for the desired antibodies. The antibodies are applied by eating the plants.
  • the monoclonal antibody technique permits preparation of a source of antibodies with extraordinary specificity.
  • Monoclonal antibodies that bind to specific molecular structures can be produced using what are today considered standard techniques.
  • the monoclonal antibodies that may be used in this invention are those that are directed to surface antigens of cariogenic organisms.
  • Surface antigens are substances that are displayed on the surface of cells. Such o antigens are accessible to antibodies present in body fluids.
  • surface antigens of cariogenic organisms are present on the surface of organisms that cause dental caries. While the role of bacterial activity in the genesis of carious lesions is well defined, establishing a cause and effect 5 relationship between a particular organism and the occurrence of dental caries has not been completely successful. To date, only S. mutans has been definitively associated with dental caries.
  • a further requirement of the monoclonal antibodies that may be used in the practice of the present invention is that they are selective for cariogenic organisms.
  • Monoclonal antibodies directed to antigens present on 5 cariogenic as well as non-cariogenic organisms may produce non-specific alterations in the makeup of the flora within the oral cavity. The consequences of such changes are not understood.
  • the preferred monoclonal antibodies are directed to surface antigens of cariogenic organisms. That is to say, the preferred ° monoclonal antibodies bind specifically to organisms that cause dental caries. It should be clearly understood that the scope of the present invention is not limited to the prevention of tooth decay in man. Monoclonal antibodies in accordance with the present invention can be genetically engineered to engage the effector response of the immune system of other mammals, such as those that are domesticated as pets.
  • Monoclonal antibodies are prepared by immunizing mice or other mammalian hosts with cell wall material isolated from cariogenic organisms.
  • the cariogenic organisms are type c S. mutans (ATCC25175).
  • the immunogenecity of molecules present in cell walls may be enhanced by a variety of techniques known in the art. In a preferred embodiment, immunogenecity of such molecules is enhanced by denaturation of the isolated cell material with formalin. Other techniques for modifying cell wall proteins to enhance immunogenecity are within the scope of this invention.
  • hosts receive one or more subsequent injections of isolated bacterial cell fragments to increase the titer of antibodies prior to sacrifice and cloning.
  • Spleen cells from hosts are harvested and cloned by limiting dilution using techniques that have become standard since the pioneering work of Kohler and Milstein.
  • surviving hybridomas are screened for antibody directed to cariogenic organisms by ELISA assay against microtiter plates coated with formalinized bacterial cell material. Positive supernatants may be subjected to further screening to identify clones that secrete antibodies with the greatest affinity for the cariogenic organisms.
  • clones with titers at least three times higher than background are screened again using an immunoprecipitation against denatured cell wall material from S. mutans.
  • three clones were identified which bound detectably only to S. mutans strains ATCC25175, LM7, OMZ175 and ATCC31377. These clones were deposited with the American Type Culture
  • a preferable approach is to use recombinant techniques to prepare chimeric antibody molecules directed specifically to surface antigens of cariogenic 5 organisms, that will also elicit an effector response from the human immune system (when used in man) upon binding to the target organism. This can be accomplished by inserting variable regions or complementarity determining o regions ("CDR's") from mouse monoclonal antibodies that are specific to cariogenic organisms into antibodies of the IgG and/or IgM classes from the mammal to be treated.
  • CDR's complementarity determining o regions
  • the antibodies are said to be "humanized.” 5
  • nucleic acid sequences that code on expression for human or humanized monoclonal antibodies to surface antigens of cariogenic organisms 1) Isolating mouse hybridomas which produce monoclonal antibodies against cariogenic organisms and cloning mouse genes that code on expression for those antibodies; 2) Using purified cariogenic organisms to screen a phage display random library made from human B ° lymphocytes to obtain genes that encode antibodies specific for cariogenic organisms; 3) Isolating human hybridomas that produce monoclonal antibodies against cariogenic organisms, using B lymphocytes recovered from heavily infected patients and cloning the human genes encoding for these antibodies; or 4) immunizing human B lymphocytes and spleen cells in vitro using purified cariogenic organisms, followed by fusion to form hybridomas to create immortal cell lines.
  • the techniques required are known to those skilled in the art.
  • mouse monoclonal antibodies are "humanized.”
  • DNA fragments encoding the variable domains of mouse hybridomas secreting antibody specific to cell surface antigens of cariogenic organisms are isolated.
  • gene cloning techniques the variable regions of human IgG and IgM immunoglobulin are replaced with the corresponding mouse variable regions or CDR's.
  • the result of this genetic engineering is a chimeric antibody molecule with variable domains that selectively bind to surface antigens of cariogenic organisms, but which interacts with the human immune system through its constant regions to trigger a humoral immune response.
  • the desired cell line transfected with IgG or IgM encoding sequences must be propagated.
  • Existing technology permits large scale propagation of monoclonal antibodies in tissue culture.
  • the transfected cell lines will secrete monoclonal antibodies into the tissue culture medium.
  • the secreted monoclonal antibodies are recovered and purified by gel filtration and related techniques of protein chemistry.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Epidemiology (AREA)
  • Birds (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Botany (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Biotechnology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Immunology (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Breeding Of Plants And Reproduction By Means Of Culturing (AREA)

Abstract

Chez l'homme, les caries dentaires peuvent être prévenues ou traitées par l'ingestion orale d'anticorps IgG et IgM monoclonaux humains ou murins humanisés qui se lient à des antigènes de surface d'organismes cariogènes, tels que S. mutans. Les anticorps monoclonaux génétiquement modifiés entrent en contact avec l'appareil effecteur du système immunitaire humain lorsqu'ils se lient aux organismes cariogènes, provoquant leur destruction. Dans un mode de réalisation préféré, les anticorps monoclonaux contre les organismes cariogènes sont produits par des plantes comestibles transformées, notamment des fruits et des légumes, des séquences d'ADN qui codent pour l'expression des anticorps voulus. L'application desdits anticorps se fait par l'ingestion des plantes.
EP00959362A 2000-08-24 2000-08-24 Methode immunologique pour la prevention des caries dentaires Withdrawn EP1313506A1 (fr)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/US2000/023277 WO2002015931A1 (fr) 2000-08-24 2000-08-24 Methode immunologique pour la prevention des caries dentaires

Publications (1)

Publication Number Publication Date
EP1313506A1 true EP1313506A1 (fr) 2003-05-28

Family

ID=21741708

Family Applications (1)

Application Number Title Priority Date Filing Date
EP00959362A Withdrawn EP1313506A1 (fr) 2000-08-24 2000-08-24 Methode immunologique pour la prevention des caries dentaires

Country Status (4)

Country Link
EP (1) EP1313506A1 (fr)
JP (1) JP2004506695A (fr)
AU (1) AU2000270698A1 (fr)
WO (1) WO2002015931A1 (fr)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030143234A1 (en) * 1999-08-20 2003-07-31 Wenyuan Shi Anti-microbial targeting chimeric pharmaceutical
US20020068066A1 (en) * 1999-08-20 2002-06-06 Wenyuan Shi Method for the treatment and prevention of dental caries
US7569542B2 (en) 1999-08-20 2009-08-04 The Regents Of The University Of California Anti-microbial targeting chimeric pharmaceutical
US7875598B2 (en) 2004-03-04 2011-01-25 The Regents Of The University Of California Compositions useful for the treatment of microbial infections
WO2008030988A2 (fr) 2006-09-06 2008-03-13 The Regents Of The University Of California Peptides antimicrobiens ciblés sélectivement et leur utilisation

Family Cites Families (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS6028937A (ja) * 1983-07-25 1985-02-14 Kitasato Inst:The 非う蝕性抗体および組成物
JPS6038329A (ja) * 1983-08-11 1985-02-27 Lion Corp う蝕予防剤
US5352446A (en) * 1986-03-25 1994-10-04 Council Of Governors Of The United Medical And Dental Schools Of Guy's And St. Thomas's Hospitals Method of treating dental caries with monoclonal antibodies against the antigen I and antigen I/II of streptococcus mutans
JP2641228B2 (ja) * 1988-01-22 1997-08-13 鐘紡株式会社 抗体およびそれを有効成分とするう蝕予防剤、並びにこれらの製造方法
JPH02177899A (ja) * 1988-12-28 1990-07-10 Nagase Sangyo Kk スオレプトコッカス・ミュータンスに特異的に反応するＩｇＤモノクローナル抗体
GB9014932D0 (en) * 1990-07-05 1990-08-22 Celltech Ltd Recombinant dna product and method
JPH05227916A (ja) * 1992-01-11 1993-09-07 Kanebo Ltd う蝕予防食品
JPH06122633A (ja) * 1992-10-09 1994-05-06 Lion Corp ストレプトコッカス・ミュータンスに対して免疫活性を有する抗体及びう蝕予防剤
US6046037A (en) * 1994-12-30 2000-04-04 Hiatt; Andrew C. Method for producing immunoglobulins containing protection proteins in plants and their use
ATE369423T1 (de) * 1994-12-30 2007-08-15 Planet Biotechnology Inc Verfahren zur herstellung von schutzproteine enthaltende immunoglobuline und ihre verwendung
AU756242B2 (en) * 1998-08-21 2003-01-09 Regents Of The University Of California, The Monoclonal antibodies specific for streptococcus mutans, and uses thereof

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO0215931A1 *

Also Published As

Publication number Publication date
JP2004506695A (ja) 2004-03-04
WO2002015931A1 (fr) 2002-02-28
WO2002015931A9 (fr) 2002-05-23
AU2000270698A1 (en) 2002-03-04

Similar Documents

Publication Publication Date Title
CA2303202C (fr) Sequences d'acides amines a usage therapeutique et prophylactique pour les maladies causees par des toxines de clostridium difficile
Ma et al. Assembly of monoclonal antibodies with IgG1 and IgA heavy chain domains in transgenic tobacco plants
US20060258848A1 (en) Human antipneumococcal antibodies from non-human animals
US9089557B2 (en) Human antibodies against Pseudomonas aeruginosa LPS derived from transgenic xenomouse
JPH06501152A (ja) 動物およびヒトにおける感染の治療および予防用の新規な抗体
KR20120003017A (ko) 클로스트리듐 디피실리 독소에 대한 항체 및 이의 용도
CN102264762A (zh) 人抗pd-1、pd-l1和pd-l2的抗体及其应用
CZ292295B6 (cs) Rekombinantní protilátková molekula, DNA sekvence, terapeutická nebo diagnostická kompozice a použití protilátkové molekuly
SK168497A3 (en) Streptococcal heat shock proteins members of the hsp70 family
JP2010503668A (ja) インフルエンザ抗体、組成物、および関連する方法
US20180237502A1 (en) Pan-ebola and pan-filovirus protective epitopes, antibodies, and antibody cocktails
US5919463A (en) Clostridium difficle toxins as mucosal adjuvants
US20020068066A1 (en) Method for the treatment and prevention of dental caries
WO2002015931A1 (fr) Methode immunologique pour la prevention des caries dentaires
AU2004297218A1 (en) Human anti-Pseudomonas-aeruginosa antibodies derived from transgenic Xenomouse
WO1994008013A1 (fr) Variantes de piline et leurs utilisations
US20210393711A1 (en) Bacteria expressing single chain antibodies against toll-like receptors
US20030157637A1 (en) Diagnostics and treatments of periodontal disease
KR100506118B1 (ko) 수막염균증 백신 조성물
AU2001288866B2 (en) Human antibodies against pseudomonas aeruginosa LPS derived from transgenic xenomouse
MXPA00002491A (en) Amino acid sequences for therapeutical and prophylactic applications to diseases due to clostridium difficile
AU2001288866A1 (en) Human antibodies against pseudomonas aeruginosa LPS derived from transgenic xenomouse
AU2002342740A1 (en) Human antipneumococcal antibodies from non-human animals

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20030321

AK Designated contracting states

Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LI LU MC NL PT SE

AX Request for extension of the european patent

Extension state: AL LT LV MK RO SI

17Q First examination report despatched

Effective date: 20040827

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 20050308