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NZ765643B2 - Anti-alpha synuclein antibodies - Google Patents
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NZ765643B2 - Anti-alpha synuclein antibodies - Google Patents

Anti-alpha synuclein antibodies Download PDF

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Publication number
NZ765643B2
NZ765643B2 NZ765643A NZ76564318A NZ765643B2 NZ 765643 B2 NZ765643 B2 NZ 765643B2 NZ 765643 A NZ765643 A NZ 765643A NZ 76564318 A NZ76564318 A NZ 76564318A NZ 765643 B2 NZ765643 B2 NZ 765643B2
Authority
NZ
New Zealand
Prior art keywords
alpha synuclein
seq
binding fragment
antibody
antigen
Prior art date
Application number
NZ765643A
Other versions
NZ765643A (en
Inventor
Terence Seward Baker
Lichtervelde Lorenzo De
Patrick Downey
Peter Charles Elliott
Marco Kriek
Daniel John Lightwood
David James Mcmillan
Kerry Louise Tyson
Original Assignee
UCB Biopharma SRL
Filing date
Publication date
Priority claimed from GBGB1720970.1A external-priority patent/GB201720970D0/en
Application filed by UCB Biopharma SRL filed Critical UCB Biopharma SRL
Publication of NZ765643A publication Critical patent/NZ765643A/en
Publication of NZ765643B2 publication Critical patent/NZ765643B2/en

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/505Medicinal preparations containing antigens or antibodies comprising antibodies
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K39/395Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A61K39/39533Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
    • A61K39/3955Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/14Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16Anti-Parkinson drugs
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/28Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/20Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/24Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/30Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/34Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/50Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/55Fab or Fab'
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/50Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C07K2317/565Complementarity determining region [CDR]
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/70Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/76Antagonist effect on antigen, e.g. neutralization or inhibition of binding
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/90Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/92Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/90Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/94Stability, e.g. half-life, pH, temperature or enzyme-resistance
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6893Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
    • G01N33/6896Neurological disorders, e.g. Alzheimer's disease

Abstract

The present invention relates to alpha synuclein binding antibodies and fragments thereof capable of binding alpha synuclein as a monomer and in fibrils and preventing alpha synuclein aggregation induced by alpha synuclein fibrils. The antibodies of the present invention are for use in the treatment of alpha synucleinopathies, including Parkinson's disease.

Claims (6)

Claims
1. An antibody or antigen-binding fragment thereof which binds to alpha synuclein wherein the antibody or fragment thereof comprises: 5 a. a light chain variable region comprising a CDR-L1 selected from SEQ ID NO: 1; a CDR-L2 according to SEQ ID NO: 2 and a CDR-L3 according to SEQ ID NO: 3; b. a heavy chain variable region comprising a CDR-H1 ing to SEQ ID NO: 4; a CDR-H2 selected from SEQ ID NO: 5 and a CDR-H3 selected from SEQ ID 10 NO: 6.
2. The antibody or antigen-binding fragment thereof according to claim 1, wherein amino acid residue glycine (Gly; G) at position 6 with reference to SEQ ID NO: 3 is replaced by alanine (Ala; A).
3. The antibody or n-binding fragment thereof ing to claim 1 or claim 2, 15 wherein the antibody or antigen-binding fragment thereof binds two or more amino acid residues of alpha synuclein between position 113 and 129 with reference to SEQ ID NO: 8, wherein the antibody or antigen-binding fragment thereof binds at least amino acid residues D119, N122 and Y125 with reference to SEQ ID NO: 8.
4. The dy or antigen-binding fragment thereof according to any one of the 20 preceding claims, wherein the dy or antigen-binding fragment: a. prevents aggregation of alpha synuclein induced by alpha synuclein fibrils; and/or b. is capable of binding alpha synuclein as a monomer and in fibrils.
5. The antibody or antigen-binding fragment thereof according to any one of the ing claims which has a higher binding affinity for alpha synuclein in fibrils 25 compared to alpha synuclein as monomer characterized by a constant of dissociation (KD) at least d higher for monomeric alpha ein than for alpha synuclein in fibrils.
6. The antibody or n-binding fragment thereof according to any one of the preceding claims which has a (KD) for alpha synuclein in fibrils of 60pM or less. 21329822_1 (GHMatters) 2.NZ
NZ765643A 2018-12-13 Anti-alpha synuclein antibodies NZ765643B2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GBGB1720970.1A GB201720970D0 (en) 2017-12-15 2017-12-15 Antibodies
PCT/EP2018/084689 WO2019115671A1 (en) 2017-12-15 2018-12-13 Anti-alpha synuclein antibodies

Publications (2)

Publication Number Publication Date
NZ765643A NZ765643A (en) 2024-11-29
NZ765643B2 true NZ765643B2 (en) 2025-03-04

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