EP2013235A1 - Procedes de traitement de la dystrophie musculaire associee a une deficience en dysferline - Google Patents

Procedes de traitement de la dystrophie musculaire associee a une deficience en dysferline

Info

Publication number
EP2013235A1
EP2013235A1 EP06769980A EP06769980A EP2013235A1 EP 2013235 A1 EP2013235 A1 EP 2013235A1 EP 06769980 A EP06769980 A EP 06769980A EP 06769980 A EP06769980 A EP 06769980A EP 2013235 A1 EP2013235 A1 EP 2013235A1
Authority
EP
European Patent Office
Prior art keywords
antibody
mammal
dysferlin
complement
antibodies
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Withdrawn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
EP06769980A
Other languages
German (de)
English (en)
Inventor
Simone Spuler
Russell Rother
Katrin Wenzel
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.)
Alexion Pharmaceuticals Inc
Original Assignee
Alexion Pharmaceuticals Inc
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 Alexion Pharmaceuticals Inc filed Critical Alexion Pharmaceuticals Inc
Publication of EP2013235A1 publication Critical patent/EP2013235A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2896—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against molecules with a "CD"-designation, not provided for elsewhere
    • 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
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/177—Receptors; Cell surface antigens; Cell surface determinants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • 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

Definitions

  • the polypeptide CD55 agonist is an antibody.
  • the antibody is a whole antibody or an antibody fragment.
  • the whole antibody or antibody fragment is the group consisting of a polyclonal antibody, a monoclonal antibody or antibody fragment, a diabody, a chimerized or chimeric antibody or antibody fragment, a humanized antibody or antibody fragment, a deimmunized human antibody or antibody fragment, a fully human antibody or antibody fragment, a single chain antibody, an Fv, an Fab, an Fab', and an F(ab') 2 .
  • the antibody is an agonistic antibody that specifically binds CD 55 and increases CD 55 activity.
  • FIGURE 4 Expression of regulatory factors in skeletal muscle of dysferlin- deficient patients and SJL/J mice (aged 20-30 wk).
  • A Unpooled TaqMan analysis of myostatin, SMAD3, SMALM, CARP, and EGRl (only human). The , y-axis demonstrates the fold change compared with healthy individuals and C57BL/6 mice, respectively.
  • B and C Double-immunofluorescent staining of SMAD2 protein (FITC) and nuclear membrane with anti-lamin AJC mAb (Cy3) on dysferlin- deficient (patient 4, Table III; B) and normal (Q human skeletal muscle.
  • FITC SMAD2 protein
  • Cy3 nuclear membrane with anti-lamin AJC mAb
  • the methods and compositions of the disclosure employ a therapeutic agent that can inhibit complement activity, such as for example, by preventing the formation of MAC; in specific embodiments, such a therapeutic agent may comprise an antibody that binds to C5 and inhibits C5 activity (for example, by preventing the cleavage of C5 into C5a and C5b).
  • C3b has multiple functions. As opsonin, it binds to bacteria, viruses and other cells and particles and tags them for removal from the circulation. C3b can also form a complex with C4b,C2a to produce C4b,2a,3b, or classical C5 convertase, which cleaves C5 into C5a (another anaphylatoxin) and C5b. Alternative C5 convertase is C3b, Bb, C3b and performs the same function. C5b combines with C6 yielding C5b,6, and this complex combines with C7 to form the ternary complex C5b,6,7. The C5b,6,7 complex binds C8 at the surface of a cell membrane. Upon binding of C9, the complete membrane attack complex (MAC) is formed (C5b-9) which mediates the lysis of foreign cells, microorganisms, and viruses.
  • MAC complete membrane attack complex
  • the present invention relates to a method for treating muscular dystrophy associated with dysferlin-deficiency by the administration of an agent capable of inhibiting complement (for example, by inhibiting the formation of MAC) to a patient in need of such treatment, hi particular embodiments, the agent inhibits the formation of the MAC by inhibiting the cleavage of C5 into C5a and C5b or the formation of C3 and/or C5 convertases.
  • a complement inhibitor may be a small molecule (up to 6,000 Da in molecular weight), a nucleic acid or nucleic acid analog, a peptidomimetic, or a macromolecule that is not a nucleic acid or a protein.
  • liquid formulations may further comprise one or more excipients such as a saccharide, an amino acid (e.g., arginine, lysine, and methionine) and a polyol.
  • excipients such as a saccharide, an amino acid (e.g., arginine, lysine, and methionine) and a polyol.
  • formulations of the subject antibodies are pyrogen- free formulations which are substantially free of endotoxins and/or related pyrogenic substances.
  • Endotoxins include toxins that are confined inside microorganisms and are released when the microorganisms are broken down or die.
  • Pyrogenic substances also include fever-inducing, thermostable substances (glycoproteins) from the outer membrane of bacteria and other microorganisms.
  • Formulations of the subject antibodies include those suitable for oral, dietary, topical, parenteral (e.g., intravenous, intraarterial, intramuscular, subcutaneous injection), ophthalmologic (e.g., topical or intraocular), inhalation (e.g., intrabronchial, intranasal or oral inhalation, intranasal drops), rectal, and/or intravaginal administration.
  • parenteral e.g., intravenous, intraarterial, intramuscular, subcutaneous injection
  • ophthalmologic e.g., topical or intraocular
  • inhalation e.g., intrabronchial, intranasal or oral inhalation, intranasal drops
  • rectal e.g., rectal, and/or intravaginal administration.
  • Other suitable methods of administration can also include rechargeable or biodegradable devices and controlled release polymeric devices.
  • Stents in particular, may be coated with a controlled release polymer mixed with an agent
  • therapeutics of the disclosure can also be administered in a variety of unit dosage forms and their dosages will also vary with the size, potency, and in vivo half-life of the particular therapeutic being administered.
  • Doses of therapeutics of the disclosure will also vary depending on the manner of administration, the particular symptoms of the patient being treated, the overall health, condition, size, and age of the patient, and the judgment of the prescribing physician.
  • DAFl SEQ ID NO.2JGTACAGGAACCCCCTCAACG (SEQ ID NO.10JTGAGGAGTTGGTTGGTCTCC (SEQ NO- IS) FAM -CAGAAACCCACAACAGAAAGTGTTCCAAAT-TAMRA NM_ 010016

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Immunology (AREA)
  • Medicinal Chemistry (AREA)
  • Organic Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Neurology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Cell Biology (AREA)
  • Zoology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Epidemiology (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Peptides Or Proteins (AREA)

Abstract

La présente invention concerne l'utilisation de traitements capables d'inhiber le complément tels qu'un anticorps anti-C5 afin de traiter une dystrophie musculaire associée à une déficience en dysferline.
EP06769980A 2006-05-01 2006-05-01 Procedes de traitement de la dystrophie musculaire associee a une deficience en dysferline Withdrawn EP2013235A1 (fr)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/US2006/016980 WO2007130031A1 (fr) 2006-05-01 2006-05-01 Procedes de traitement de la dystrophie musculaire associee a une deficience en dysferline

Publications (1)

Publication Number Publication Date
EP2013235A1 true EP2013235A1 (fr) 2009-01-14

Family

ID=37866247

Family Applications (1)

Application Number Title Priority Date Filing Date
EP06769980A Withdrawn EP2013235A1 (fr) 2006-05-01 2006-05-01 Procedes de traitement de la dystrophie musculaire associee a une deficience en dysferline

Country Status (4)

Country Link
EP (1) EP2013235A1 (fr)
AU (1) AU2006343402A1 (fr)
CA (1) CA2650718A1 (fr)
WO (1) WO2007130031A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10590189B2 (en) 2006-03-15 2020-03-17 Alexion Pharmaceuticals, Inc. Treatment of paroxysmal nocturnal hemoglobinuria patients by an inhibitor of complement

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20090041764A1 (en) * 2006-10-20 2009-02-12 Alexion Pharmaceuticals, Inc. Methods for the treatment of muscular dystrophy associated with dysferlin-deficiency
SI2894165T1 (sl) * 2008-11-10 2023-04-28 Alexion Pharmaceuticals, Inc. Postopki in sestavki za zdravljenje motenj povezanih s komplementom

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6074642A (en) * 1994-05-02 2000-06-13 Alexion Pharmaceuticals, Inc. Use of antibodies specific to human complement component C5 for the treatment of glomerulonephritis

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO2007130031A1 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10590189B2 (en) 2006-03-15 2020-03-17 Alexion Pharmaceuticals, Inc. Treatment of paroxysmal nocturnal hemoglobinuria patients by an inhibitor of complement
US10703809B1 (en) 2006-03-15 2020-07-07 Alexion Pharmaceuticals, Inc. Treatment of paroxysmal nocturnal hemoglobinuria patients by an inhibitor of complement

Also Published As

Publication number Publication date
AU2006343402A1 (en) 2007-11-15
WO2007130031A1 (fr) 2007-11-15
CA2650718A1 (fr) 2007-11-15

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