Ablynx N.v.

Sanofi

Ann Brigé

Sigrid Cornelis

Heidi Rommelaere

Eric Lorent

Marc Jozef Lauwereys

Christine Labeur

Bruno Dombrecht

John Edward Park

Bernd Weigle

Klaus Erb

Melanie Rieger

Timothy Soos

Veronique De Brabandere

Peter Schotte

Mauro Sergi

Christian Asbrand

Filip Callewaert

Hans Ulrichts

Bart Walcarius

Nadine Biesemann

Karen Heyninck

Shanna Van Zwam

Yves Meyvis

The present technology aims at providing a novel type of drug for treating a subject suffering from an inflammatory disease. Specifically, the present technology provides polypeptides comprising at least four immunoglobulin single variable domains (ISVDs), characterized in that at least two ISVDs bind to IL-13 and at least two ISVDs binds to TSLP. The present technology also provides nucleic acids, vectors and compositions.

Nucleic acids encoding polypeptides comprising immunoglobulin single variable domains targeting IL-13 and TSLP

The present disclosure provides a novel type of drug for treating a subject suffering from an inflammatory and/or autoimmune disease, and specifically rheumatoid arthritis. Specifically, the disclosure provides polypeptides comprising at least three immunoglobulin single variable domains (ISVDs), characterized in that at least one ISVD binds to TNF-α and at least two ISVDs bind to IL-6. The present disclosure also provides nucleic acids, vectors and compositions.

Polypeptides comprising immunoglobulin single variable domains targeting IL-6 and TNF-α

Methods of treating asthma with polypeptides targeting IL-13 and TSLP

The present technology aims at providing a novel type of drug. Specifically, the present technology provides polypeptides comprising at least three immunoglobulin single variable domains (ISVDs), characterized in that at least one ISVD binds to TNF&#x3b1; and at least two ISVDs bind to IL-23. The present technology also provides nucleic acids, vectors and compositions.

Polypeptides comprising immunoglobulin single variable domains targeting TNFA and IL-23

Polypeptides comprising immunoglobulin single variable domains targeting IL-13 and TSLP

In a broad aspect the present invention generally relates to novel dimer-complexes (herein called 'non-fused-dimers' or NFDs) comprising single variable domains, methods of making these complexes and uses thereof. These non-covalently bound dimer-complexes consist of two identical monomers that each comprises of one or more single variable domains (homodimers) or of two different monomers that each comprises on or more single variable domains (heterodimers). The subject NFDs have typically altered e.g. improved binding characteristics over their monomeric counterpart. The NFDs of the invention may further be engineered through linkage by a flexible peptide or cysteines in order to improve the stability. This invention also describes conditions under which such NFDs are formed and conditions under which the formation of such dimers can be avoided.

Antigen binding dimer-complexes, methods of making/avoiding and uses thereof

The present invention relates to stable formulations of polypeptides, e.g. immunoglobulin single variable domains, in particular immunoglobulin single variable domains directed against von Willebrand Factor (vWF). The invention provides formulations which are stable upon storage for prolonged periods of time and over a broad range of temperatures. The formulations of the invention ensure a high stability of the polypeptide, allowing multiple freeze-thaw cycles without chemical or physical deterioration, and provide stability in relation to mechanical stress, such as shake, shear or stir stress. They are suitable for pharmaceutical and diagnostic preparations and compatible with pharmaceutically acceptable diluents.

Stable formulations of immunoglobulin single variable domains

In a broad aspect the present invention generally relates to novel dimer-complexes (herein called 'non-fused-dimers' or NFDs) comprising single variable domains, methods of making these complexes and uses thereof. These non-covalently bound dimer-complexes consist of two identical monomers that each comprises of one or more single variable domains (homodimers) or of two different monomers that each comprises on or more single variable domains (heterodimers). The subject NFDs have typically altered e.g. improved binding characteristics over their monomelic counterpart. The NFDs of the invention may further be engineered through linkage by a flexible peptide or cysteines in order to improve the stability. This invention also describes conditions under which such NFDs are formed and conditions under which the formation of such dimers can be avoided.

Stable formulations are provided that contain immunoglobulin single variable domains at a high concentration. The formulations are useful as pharmaceutical formulation and suitable for subcutaneous administration. The formulations can be transported and stored under various stress conditions. The invention further relates to containers and pharmaceutical units comprising such formulations and to methods for preparing and prophylactic and therapeutic uses of the formulations and pharmaceutical units of the invention.

Stable formulations of polypeptides and uses thereof

Methods are provided for the expression of immunoglobulin variable domains that are secreted into the culture medium. The methods provide for the production of homogeneous immunoglobulin variable domains in which the proportion of product-related variants that comprise, at the N-terminus, at least one redundant amino acid residue derived from the secretion signal is strongly reduced or absent.

Method for the production of immunoglobulin single variable domains

Formulations are provided that contain single variable domains with a good solubility and good stability under different storage, transportation and stress conditions. The formulations are useful as pharmaceutical formulation. The formulation comprises an aqueous carrier with a pH of 5.5 to 8.0, a buffer selected from the group consisting of histidine pH 6.0-6.5, hepes pH 7.0-8.0, MES pH 6.0, succinate pH 6.0-6.5 and acetate pH 5.5-6.0; an excipient; and/or a surfactant selected from polysorbate 80, polysorbate 20 and poloxamers. The formulation is further characterized that it has an inorganic salt concentration of 150 mM or lower.

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Ertvelde, Belgium

Ann Brigé