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WO1996037225A1 - Procede de traitement du lupus erythemateux dissemine - Google Patents

Procede de traitement du lupus erythemateux dissemine Download PDF

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Publication number
WO1996037225A1
WO1996037225A1 PCT/US1996/007597 US9607597W WO9637225A1 WO 1996037225 A1 WO1996037225 A1 WO 1996037225A1 US 9607597 W US9607597 W US 9607597W WO 9637225 A1 WO9637225 A1 WO 9637225A1
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WO
WIPO (PCT)
Prior art keywords
dsdna
antibodies
antibody
protein
dna
Prior art date
Application number
PCT/US1996/007597
Other languages
English (en)
Inventor
Morris Reichlin
Kensei Tsuzaka
Wei Zhang
Original Assignee
Oklahoma Medical Research Foundation
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 Oklahoma Medical Research Foundation filed Critical Oklahoma Medical Research Foundation
Priority to AU73494/96A priority Critical patent/AU7349496A/en
Publication of WO1996037225A1 publication Critical patent/WO1996037225A1/fr
Priority to US09/768,155 priority patent/US20020155105A1/en

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
    • C07K14/4713—Autoimmune diseases, e.g. Insulin-dependent diabetes mellitus, multiple sclerosis, rheumathoid arthritis, systemic lupus erythematosus; Autoantigens
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/42—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against immunoglobulins
    • C07K16/4208—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against immunoglobulins against an idiotypic determinant on Ig
    • C07K16/4241—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against immunoglobulins against an idiotypic determinant on Ig against anti-human or anti-animal Ig
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/10—Musculoskeletal or connective tissue disorders
    • G01N2800/101—Diffuse connective tissue disease, e.g. Sjögren, Wegener's granulomatosis
    • G01N2800/104—Lupus erythematosus [SLE]

Definitions

  • the present invention includes methods and reagents for treatment of Systemic Lupus Erythematosus ("SLE") patients characterized double stranded (ds) DNA by administration of reagents reactive with doublestranded DNA antibodies to alleviate damage resulting from the antibodies.
  • SLE Systemic Lupus Erythematosus
  • a humanized antibody is one in which only the antigen-recognized sites, or complementarily-determining hypervariable regions (CDRs) are of non-human origin, whereas all framework regions (FR) of variable domains are products of human genes .
  • CDRs complementarily-determining hypervariable regions
  • FR framework regions
  • the CDRs are grafted onto human heavy chain variable region framework by the use of synthetic oligonucleotides and polymerase chain reaction (PCR) recombination. Codons for the animal heavy chain CRDs, as well as the available human heavy chain variable region framework, are built in four (each 100 bases long) oligonucleotides. Using PCR, a grafted D ⁇ A sequence of 400 bases is formed that encodes for the recombinant animal CDR/human heavy chain FR protection.
  • PCR polymerase chain reaction
  • a cDNA insert isolated from a recombinant phage was digested with several restriction enzymes (Bgl II, EcoRV, Pst I, and
  • 104 kDa protein at least in MOLT4 cell extract is the responsible protein of which G7 encodes a portion.
  • anti-dsDNA antibodies have high frequencies of basic amino acids carrying positive charges in the heavy chain complementarity determining regions and that arginine is the most versatile amino acid for binding with negative-charged DNA (31) .
  • negative-charged DNA 311
  • cross-reactions between anti-dsDNA antibody and Hsl are not dependent on charge interaction in the primary sequence alone but rather that the cross-reactive epitope depends on conformational apposition of negative charges in the tertiary structure of HS1.
  • HS1 mimics DNA because anti-dsDNA antibodies cross-react with HS1.
  • 33.H11 and 33.C9 are IgG monoclonal anti-dsDNA antibodies (Winkler, et al. , Clin . Exp . Immunol . 85:379 (1991)) and strongly recognized the protein expressed by G7.
  • 33.H11 did not show a homogeneous nuclear pattern and the homogeneous nuclear staining patterns of 33.C9 was not inhibited by G7-RP but was inhibited by as little as 1.0 ⁇ g/ml of DNA.
  • RNA-IP A quantity (0.1 ⁇ g) of the human IgG monoclonal anti-dsDNA Ab 33.H11 (Winker, et al. 1991) was preincubated in 500 ⁇ l of NET-2 with 100 ⁇ g/ml of calf thymus dsDNA (or Yeast tRNA as a negative control) or 100 ⁇ g/ml of G7-RP (or BSA as a negative control) before RNA-IP was performed as described above.
  • RNA-IP by 33.H11 which was preincubated with calf thymus dsDNA or Yeast tRNA, labeled cell extract and washed beds were not treated with RQ1 DNase.
  • polyacrylamide non-denaturing gel 33.H11 IgG (1.0 ⁇ g) ; anti-dsDNA-positive patient sera LG, CC, JP, IL, respectively; normal human serum DB; normal human IgG from Con fraction II (1.0 ⁇ g) ; affinity- purified anti-dsDNA IgG (1.0 ⁇ g each) from sera LG,
  • the r-protein SI in E. coli is well known to be associated with the 3OS ribosomal subunit via its N-terminal globular domain. It has been reported that the major function of r-protein SI of E. coli . in protein synthesis is at the mRNA binding step, as described by Subramanian, Prog. Nucleic Acids Res . Mol. Biol. 28:101 (1983) . Thus this protein plays a key role in translation initiation of E. coli . The translation inhibition of globin mRNA by anti-dsDNA antibodies was then determined. There are to our knowledge no published studies describing a role for r-protein SI or its analogue in eukaryotic cells but these experiments suggest such a role.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Immunology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Medicinal Chemistry (AREA)
  • Molecular Biology (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Rehabilitation Therapy (AREA)
  • Rheumatology (AREA)
  • Toxicology (AREA)
  • Zoology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Abstract

Des traitements ont été mis au point pour des patients souffrant de lupus, ces traitements utilisant soit des anticorps anti-ID contre les ADNdb (ADN double brin), pour bloquer les anticorps anti-ADNdb et/ou détruire les lymphocytes B produisant les anticorps anti-ADNdb, soit des peptides de protéines ribosomiques S1 capables d'entrer en immunoréaction avec les anticorps anti-ADNdb. Les exemples montrent que: (1) les anticorps anti-ADNdb sont capables d'entrer en réaction croisée avec les protéines ribosomiques S1; (2) les anticorps anti-ADNdb suppriment la synthèse de protéines, probablement par inhibition de l'initiation de la translation d'ARNm; et (3) un sérum humain normal contient un anticorps anti-idiotypique (anti-Id) contre les anticorps anti-ADNdb isolés chez des patients souffrant du lupus érythémateux disséminé, anticorps qui ont bloqué les interactions entre le fragment d'anticorps anti-Id (Fab2) et diverses préparations anti-ADNdb.
PCT/US1996/007597 1995-05-25 1996-05-24 Procede de traitement du lupus erythemateux dissemine WO1996037225A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
AU73494/96A AU7349496A (en) 1995-05-25 1996-05-24 Method for treatment of SLE
US09/768,155 US20020155105A1 (en) 1996-02-16 2001-01-23 Method for treatment of SLE

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US45018895A 1995-05-25 1995-05-25
US450,188 1995-05-25
US60/011,867 1996-02-15
US1186796P 1996-02-16 1996-02-16

Publications (1)

Publication Number Publication Date
WO1996037225A1 true WO1996037225A1 (fr) 1996-11-28

Family

ID=26682878

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1996/007597 WO1996037225A1 (fr) 1995-05-25 1996-05-24 Procede de traitement du lupus erythemateux dissemine

Country Status (2)

Country Link
AU (1) AU7349496A (fr)
WO (1) WO1996037225A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7192715B2 (en) 1993-11-30 2007-03-20 Oklahoma Medical Research Foundation Diagnostics and therapy of epstein-barr virus in autoimmune disorders
US7273613B1 (en) 1997-01-13 2007-09-25 The Board of Regents, The University of Oklahoma Diagnostics and therapy of Epstein-Barr virus in autoimmune disorders

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0113431A2 (fr) * 1982-12-03 1984-07-18 Yeshiva University Anticorps monoclonaux, réactifs avec des idiotypes communs aux anticorps humains de ADN native provenant de patients atteints de lupus érythémateux systémique
WO1994021669A1 (fr) * 1993-03-18 1994-09-29 Medclone, Inc. Antigene relatif a des maladies inflammatoires

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0113431A2 (fr) * 1982-12-03 1984-07-18 Yeshiva University Anticorps monoclonaux, réactifs avec des idiotypes communs aux anticorps humains de ADN native provenant de patients atteints de lupus érythémateux systémique
WO1994021669A1 (fr) * 1993-03-18 1994-09-29 Medclone, Inc. Antigene relatif a des maladies inflammatoires

Non-Patent Citations (7)

* Cited by examiner, † Cited by third party
Title
B. HAHN: "Suppression of autoimmune diseases with anti-idiotypic antibodies: Murine lupus nephritis as a model.", SPRINGER SEMINARS IN IMMUNOPATHOLOGY, vol. 7, no. 1, 1984, BERLIN, GERMANY, pages 25 - 34, XP000605499 *
C. MORLAND ET AL.: "Anti-idiotype and immunosuppressant treatment of murine lupus.", CLINICAL AND EXPERIMENTAL IMMUNOLOGY, vol. 83, no. 1, January 1991 (1991-01-01), OXFORD, GB, pages 126 - 132, XP000608102 *
C. RAVIRAJAN ET AL.: "Involvement in lupus disease of idiotypes Id.F-423 and Id.IV-228 defined, respectively, upon foetal and adult MRL/Mp-lpr/lpr DNA-binding monoclonal autoantibodies.", IMMUNOLOGY, vol. 74, no. 2, October 1991 (1991-10-01), OXFORD, GB, pages 342 - 347, XP000608109 *
D. GRABOWSKI ET AL.: "Drosophila AP3, a presumptive DNA repair protein, is homologous to human ribosomal associated protein PO.", NUCLEIC ACIDS RESEARCH, vol. 19, no. 15, 11 August 1987 (1987-08-11), OXFORD, GB, pages 4297, XP002016365 *
K. TSUZUKA ET AL.: "Lupus autoantibodies to double-stranded DNA cross-react with ribosomal protein S1.", ARTHRITIS & RHEUMATISM, vol. 38, no. 9 suppl., September 1995 (1995-09-01), NEW YORK, NY, USA, pages S274, XP000608103 *
K. TSUZUKA ET AL.: "Lupus autoantibodies to double-stranded DNA cross-react with ribosomal protein S1.", THE JOURNAL OF IMMUNOLOGY, vol. 156, no. 4, 15 February 1996 (1996-02-15), BALTIMORE, MD, USA, pages 1668 - 1675, XP002016366 *
T. SASAKI ET AL.: "In vitro manipulation of human anti-DNA antibody production by anti-idiotypic antibodies conjugated with neocarzinostatin.", THE JOURNAL OF IMMUNOLOGY, vol. 142, no. 4, 15 February 1989 (1989-02-15), BALTIMORE, MD, USA, pages 1159 - 1165, XP002016364 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7192715B2 (en) 1993-11-30 2007-03-20 Oklahoma Medical Research Foundation Diagnostics and therapy of epstein-barr virus in autoimmune disorders
US7273613B1 (en) 1997-01-13 2007-09-25 The Board of Regents, The University of Oklahoma Diagnostics and therapy of Epstein-Barr virus in autoimmune disorders

Also Published As

Publication number Publication date
AU7349496A (en) 1996-12-11

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