Binding constructs and methods for use thereof

C - Chemistry – Metallurgy – 07 – K

Patent

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Details

C07K 16/46 (2006.01) A61K 39/395 (2006.01) C07K 16/00 (2006.01) C07K 16/28 (2006.01) C07K 16/30 (2006.01) C12N 15/13 (2006.01)

Patent

CA 2533921

The invention relates to novel binding domain-immunoglobulin fusion proteins that feature a binding domain for a cognate structure such as an antigen, a counterreceptor or the like, a wild-type IgG, IGA or IgE hinge-acting region, i.e., IgE CH2, region polypeptide or a mutant IgGI hinge region polypeptide having either zero, one or two cysteine residues, and immunoglobulin CH2 and CH3 domains, and that are capable of ADCC and/or CDC while occurring predominantly as polypeptides that are compromised in their ability to form disulfide-linked multimers. The fusion proteins can be recombinantly produced at high expression levels. Also provided are related compositions and methods, including cell surface forms of the fusion proteins and immunotherapeutic applications of the fusion proteins and of polynucleotides encoding such fusion proteins.

La présente invention concerne de nouvelles protéines hybrides d'immunoglobuline à domaine de liaison qui comprennent un domaine de liaison pour une structure de même origine telle qu'un antigène, un contre-récepteur ou similaire, un IgG de type sauvage, un IGA ou une région agissant sur la charnière IgE, c'est-à-dire, IgE CH2, un polypeptide de région ou un polypeptide mutant de région charnière IgGI comportant zéro, un ou deux résidus cystéine et les domaines CH2 et CH3 d'immunoglobuline et qui sont capables de ADCC et/ou de CDC tout en se présentant de manière prédominante sous forme de polypeptides qui sont affaiblis dans leur capacité à former des multimères liés par disulfure. Les protéines hybrides peuvent être produites par recombinaison à des niveaux d'expression élevés. La présente invention concerne des compositions et des procédés, y compris des formes de surface cellulaire des protéines hybrides et des applications immunothérapeutiques des protéines hybrides et des polynucléotides codant de telles protéines hybrides.

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