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1. WO2011076684 - SEQUENCE DEPENDENT AGGREGATION

Publication Number WO/2011/076684
Publication Date 30.06.2011
International Application No. PCT/EP2010/070063
International Filing Date 17.12.2010
IPC
C07K 16/00 2006.01
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
KPEPTIDES
16Immunoglobulins, e.g. monoclonal or polyclonal antibodies
C07K 16/28 2006.01
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
KPEPTIDES
16Immunoglobulins, e.g. monoclonal or polyclonal antibodies
18against material from animals or humans
28against receptors, cell surface antigens or cell surface determinants
CPC
C07K 16/00
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
KPEPTIDES
16Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
C07K 16/2866
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
KPEPTIDES
16Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
18against material from animals or humans
28against receptors, cell surface antigens or cell surface determinants
2866against receptors for cytokines, lymphokines, interferons
C07K 16/2875
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
KPEPTIDES
16Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
18against material from animals or humans
28against receptors, cell surface antigens or cell surface determinants
2875against the NGF/TNF superfamily, e.g. CD70, CD95L, CD153, CD154
C07K 16/461
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
KPEPTIDES
16Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
46Hybrid immunoglobulins
461Igs containing Ig-regions, -domains or -residues form different species
C07K 2317/24
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
KPEPTIDES
2317Immunoglobulins specific features
20characterized by taxonomic origin
24containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
C07K 2317/567
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
KPEPTIDES
2317Immunoglobulins specific features
50characterized by immunoglobulin fragments
56variable (Fv) region, i.e. VH and/or VL
567Framework region [FR]
Applicants
  • F. Hoffmann-La Roche AG (AllExceptUS)
  • KETTENBERGER, Hubert [DE]/[DE] (UsOnly)
  • KLOSTERMANN, Stefan [DE]/[DE] (UsOnly)
  • KOHNERT, Ulrich [DE]/[DE] (UsOnly)
  • NEUMANN, Sebastian [DE]/[DE] (UsOnly)
Inventors
  • KETTENBERGER, Hubert
  • KLOSTERMANN, Stefan
  • KOHNERT, Ulrich
  • NEUMANN, Sebastian
Agents
  • BURGER, Alexander
Priority Data
09015832.022.12.2009EP
Publication Language English (EN)
Filing Language English (EN)
Designated States
Title
(EN) SEQUENCE DEPENDENT AGGREGATION
(FR) AGRÉGATION DÉPENDANTE DE LA SÉQUENCE
Abstract
(EN)
Herein is reported a method for reducing the aggregation of an immunoglobulin in solution comprising the steps of i) comparing the amino acid sequence of the fourth framework region of the heavy chain of an antibody with a reference or germline sequence and determining whether one or more threonine residues and/or serine residues have been replaced by a different amino acid residue, and ii) modifying the amino acid sequence of the immunoglobulin by reverting the exchanged threonine residues and/or serine residues back to threonine or serine of the reference or germline sequence and thereby reducing the aggregation of an immunoglobulin in solution.
(FR)
L'invention concerne un procédé de réduction de l'agrégation d'une immunoglobuline en solution comprenant les étapes suivantes : i) la comparaison de la séquence d'acides aminés de la quatrième région de charpente de la chaîne lourde d'un anticorps avec une séquence de référence ou de lignée germinale et la détermination si un ou plusieurs résidus de thréonine et/ou résidus de sérine ont été remplacés par un résidu d'acide aminé différent, et ii) la modification de la séquence d'acides aminés de l'immunoglobuline en inversant les résidus de thréonine et/ou les résidus de sérine échangés pour revenir à la thréonine ou à la sérine de la séquence de référence ou de lignée germinale et la réduction de cette manière de l'agrégation d'une immunoglobuline en solution.
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