WO2023148397 - ENGINEERED STABILIZING AGLYCOSYLATED FC-REGIONS
National phase entry:
Publication Number
WO/2023/148397
Publication Date
10.08.2023
International Application No.
PCT/EP2023/052940
International Filing Date
07.02.2023
Title **
[English]
ENGINEERED STABILIZING AGLYCOSYLATED FC-REGIONS
[French]
STABILISATION MODIFIÉE DE RÉGIONS FC AGLYCOSYLÉES
Applicants **
VIB VZW
Suzanne Tassierstraat 1
9052 Gent, BE
UNIVERSITEIT GENT
Sint-Pietersnieuwstraat 25
9000 Gent, BE
Inventors
CALLEWAERT, Nico
Begijnhoflaan 15
9850 Nevele, BE
VAN SCHIE, Loes
Pieter Van Vyncktstraat 33K
9032 Gent, BE
LONIGRO, Chiara
Koningsdal 23/201
9000 Gent, BE
WEYTS, Wannes
Striemenbergstraat 5
9040 Gent, BE
SCHEPENS, Bert
Elshout 1
9031 Drongen, BE
Priority Data
22155324.1
07.02.2022
EP
Application details
| Total Number of Claims/PCT | * |
| Number of Independent Claims | * |
| Number of Priorities | * |
| Number of Multi-Dependent Claims | * |
| Number of Drawings | * |
| Pages for Publication | * |
| Number of Pages with Drawings | * |
| Pages of Specification | * |
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International Searching Authority |
EPO
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| Applicant's Legal Status |
Legal Entity
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| Entry into National Phase under |
Chapter I
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| Translation |
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Recalculate
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Quotation for National Phase entry
| Country | Stages | Total | |
|---|---|---|---|
| China | Filing | 1140 | |
| EPO | Filing, Examination | 4743 | |
| Japan | Filing | 591 | |
| South Korea | Filing | 575 | |
| USA | Filing, Examination | 3910 |
Total: 10959 USD
The term for entry into the National Phase has expired. This quotation is for informational purposes only
Abstract[English]
The invention relates to the field of therapeutic antibody development. The present invention relates to a mutant Fc domain based on the human IgG1 constant domain, whereby the mutations comprise a substitution of the asparagine at position 297 with an alanine, to prevent N-glycosylation, and additionally comprise two amino acid substitutions at position R292 and V302 with a cysteine as to increase the stability of those aglycosylated Fc-containing proteins by forming an additional disulfide bridge upon expression in a host. More specifically, the introduction of this specific combination of mutations allows for aglycosylated Fc-region containing protein production in yeast with favorable biophysical characteristics, and for which the stability is at least comparable to the stability observed for conventional non-mutated Fcs. Even more specifically, immunoglobulin single variable domains (ISVDs), or VHHs, fused to said stabilizing aglycosylated Fc-regions are provided herein, for use as a medicament and in treatment of diseases, such as Covid-19.[French]
L'invention relève du domaine du développement d'anticorps thérapeutiques. La présente invention concerne un domaine Fc mutant basé sur le domaine constant d'IgG1 humaine, les mutations comprenant une substitution de l'asparagine en position 297 par une alanine, pour empêcher la N-glycosylation, et comprenant en outre deux substitutions d'acides aminés en position R292 et V302 avec une cystéine pour augmenter la stabilité de ces protéines contenant Fc aglycosylées par formation d'un pont disulfure supplémentaire lors de l'expression dans un hôte. Plus particulièrement, l'introduction de cette combinaison spécifique de mutations permet la production de protéines contenant une région Fc aglycosylée dans une levure ayant des caractéristiques biophysiques favorables, et pour laquelle la stabilité est au moins comparable à la stabilité observée pour des Fc non mutés classiques. Plus particulièrement encore, l'invention concerne des domaines variables uniques d'immunoglobuline (ISVD) ou des VHH, fusionnés auxdites régions Fc aglycosylées stabilisantes, destinés à être utilisés en tant que médicament et dans le traitement de maladies, telles que la covid-19.