Ablynx N.v.

Sanofi

Peter Schotte

Carlo Boutton

Bruno Dombrecht

Cedric Jozef Neotere Ververken

Marie-Ange Buyse

Judith Baumeister

Stephanie Staelens

Soren Steffensen

Guy Hermans

Veerle Snoeck

Gerald Beste

Alexander Szyroki

Tinneke Denayer

Marie-Paule Lucienne Armanda Bouche

Daniel Janssen

Peter Casteels

Francis Descamps

Marc Jozef Lauwereys

Christine Labeur

Patrick Stanssens

Jean-Luc Jonniaux

Manu De Groeve

Diane Van Hoorick

Ann Brigé

Veronique De Brabandere

Jan Pype

Bart Walcarius

Hilde Stals

Evelyne Dombrecht

Bram Laukens

Paolo Meoni

Lily Pao

Benedikte Serruys

Ana Paula Vintem

Cedric Jozef Ververken

Cedric Jozef Néotére Ververken

The present invention relates to dimers comprising a first polypeptide and a second polypeptide, wherein each of said first and second polypeptide comprises at least one immunoglobulin single variable domain (ISVD) and a C-terminal extension comprising a cysteine moiety (preferably at the C-terminus), wherein said first polypeptide and said second polypeptide are covalently linked via a disulfide bond between the cysteine moiety of said first polypeptide and the cysteine moiety of said second polypeptide, in which the dimer outperformed the benchmark constructs, e.g. cognate multivalent and multispecific constructs, in various assays. The present invention provides methods for making the dimers of the invention.

Cysteine linked nanobody dimers

The present invention relates to a method for producing a domain antibody in a yeast, wherein the formation of disulfide bridges in the domain antibody is promoted. The method encompasses the addition of oxidizing agents, preferably oxidizing metal ions, preferably one or more selected from Cu2+, Fe2+, Fe3+ and Zn2+.

Method for the production of domain antibodies

This invention provides, and in certain specific but non-limiting aspects relates to: assays that can be used to predict whether a given ISV will be subject to protein interference as described herein and/or give rise to an (aspecific) signal in such an assay (such as for example in an ADA immunoassay). Such predictive assays could for example be used to test whether a given ISV could have a tendency to give rise to such protein interference and/or such a signal; to select ISV's that are not or less prone to such protein interference or to giving such a signal; as an assay or test that can be used to test whether certain modification(s) to an ISV will (fully or partially) reduce its tendency to give rise to such interference or such a signal; and/or as an assay or test that can be used to guide modification or improvement of an ISV so as to reduce its tendency to give rise to such protein interference or signal;—methods for modifying and/or improving ISV's to as to remove or reduce their tendency to give rise to such protein interference or such a signal;—modifications that can be introduced into an ISV that remove or reduce its tendency to give rise to such protein interference or such a signal; ISV's that have been specifically selected (for example, using the assay(s) described herein) to have no or low(er)/reduced tendency to give rise to such protein interference or such a signal; modified and/or improved ISV's that have no or a low(er)/reduced tendency to give rise to such protein interference or such a signal.

Techniques for predicting, detecting and reducing aspecific protein interference in assays involving immunoglobulin single variable domains

The present technology aims at providing a novel type of drug for treating a subject suffering from cancer. Specifically, the technology provides polypeptides comprising at least four immunoglobulin single variable domains (ISVDs), characterized in that one ISVD binds to TCR and at least two ISVDs bind to GPC3. The present technology also provides nucleic acids, vectors and compositions.

Polypeptides comprising immunoglobulin single variable domains targeting glypican-3 and T cell receptor

Methods are provided for the manufacture of polypeptides comprising at least one immunoglobulin variable domain that result in an increased yield. The methods are based on simultaneous enhancement of one or more auxiliary proteins in the host.

Method for the production of immunoglobulin single variable domains

This invention provides, and in certain specific but non-limiting aspects relates to: assays that can be used to predict whether a given ISV will be subject to protein interference as described herein and/or give rise to an (aspecific) signal in such an assay (such as for example in an ADA immunoassay). Such predictive assays could for example be used to test whether a given ISV could have a tendency to give rise to such protein interference and/or such a signal; to select ISV's that are not or less prone to such protein interference or to giving such a signal; as an assay or test that can be used to test whether certain modification(s) to an ISV will (fully or partially) reduce its tendency to give rise to such interference or such a signal; and/or as an assay or test that can be used to guide modification or improvement of an ISV so as to reduce its tendency to give rise to such protein interference or signal; methods for modifying and/or improving ISV's to as to remove or reduce their tendency to give rise to such protein interference or such a signal; modifications that can be introduced into an ISV that remove or reduce its tendency to give rise to such protein interference or such a signal; ISV's that have been specifically selected (for example, using the assay(s) described herein) to have no or low(er)/reduced tendency to give rise to such protein interference or such a signal; modified and/or improved ISV's that have no or a low(er)/reduced tendency to give rise to such protein interference or such a signal.

The present invention relates to dimers comprising a first polypeptide and a second polypeptide, wherein each of said first and second polypeptide comprises at least one immunoglobulin single variable domain (1ISVD) and a C-terminal extension comprising a cysteine moiety (preferably at the C-terminus), wherein said first polypeptide and said second polypeptide are covalently linked via a disulfide bond between the cysteine moiety of said first polypeptide and the cysteine moiety of said second polypeptide, in which the dimer outperformed the benchmark constructs, e.g. cognate multivalent and multispecific constructs, in various assays. The present invention provides methods for making the dimers of the invention.

This invention provides, and in certain specific but non-limiting aspects relates to: assays that can be used to predict whether a given ISV will be subject to protein interference and/or give rise to an (aspecific) signal in such an assay (such as in an ADA immunoassay; methods for modifying and/or improving ISV's to as to remove or reduce their tendency to give rise to such protein interference or such a signal; modifications that can be introduced into an ISV that remove or reduce its tendency to give rise to such protein interference or such a signal; ISV's that have been specifically selected (for example, using the assay(s) described herein) to have no or low(er)/reduced tendency to give rise to such protein interference or such a signal; modified and/or improved ISV's that have no or a low(er)/reduced tendency to give rise to such protein interference or such a signal.

Serum albumin binding proteins containing immunoglobulin single variable domains

This invention provides, and in certain specific but non-limiting aspects relates to: &#x2014;assays that can be used to predict whether a given ISV will be subject to protein interference as described herein and/or give rise to an (aspecific) signal in such an assay (such as for example in an ADA immunoassay). Such predictive assays could for example be used to test whether a given ISV could have a tendency to give rise to such protein interference and/or such a signal; to select ISV's that are not or less prone to such protein interference or to giving such a signal; as an assay or test that can be used to test whether certain modification(s) to an ISV will (fully or partially) reduce its tendency to give rise to such interference or such a signal; and/or as an assay or test that can be used to guide modification or improvement of an ISV so as to reduce its tendency to give rise to such protein interference or signal; &#x2014;methods for modifying and/or improving ISV's to as to remove or reduce their tendency to give rise to such protein interference or such a signal; &#x2014;modifications that can be introduced into an ISV that remove or reduce its tendency to give rise to such protein interference or such a signal; &#x2014;ISV's that have been specifically selected (for example, using the assay(s) described herein) to have no or low(er)/reduced tendency to give rise to such protein interference or such a signal; &#x2014;modified and/or improved ISV's that have no or a low(er)/reduced tendency to give rise to such protein interference or such a signal.

Nanobody dimers linked via C-terminally engineered cysteins

This invention provides, and in certain specific but non-limiting aspects relates to: assays that can be used to predict whether a given ISV will be subject to protein interference as described herein and/or give rise to an (aspecific) signal in such an assay (such as for example in an ADA immunoassay). Such predictive assays could for example be used to test whether a given ISV could have a tendency to give rise to such protein interference and/or such a signal; to select ISV's that are not or less prone to such protein interference or to giving such a signal; as an assay or test that can be used to test whether certain modification(s) to an ISV will (fully or partially) reduce its tendency to give rise to such interference or such a signal; and/or as an assay or test that can be used to guide modification or improvement of an ISV so as to reduce its tendency to give rise to such protein interference or signal; &#x2014;methods for modifying and/or improving ISV's to as to remove or reduce their tendency to give rise to such protein interference or such a signal; &#x2014;modifications that can be introduced into an ISV that remove or reduce its tendency to give rise to such protein interference or such a signal; ISV's that have been specifically selected (for example, using the assay(s) described herein) to have no or low(er)/reduced tendency to give rise to such protein interference or such a signal; modified and/or improved ISV's that have no or a low(er)/reduced tendency to give rise to such protein interference or such a signal.

The present invention relates to amino acid sequences that are capable of binding to serum albumin; to proteins and polypeptides comprising or essentially consisting of such amino acid sequences; to nucleic acids that encode such amino acid sequences, proteins or polypeptides; to compositions, and in particular pharmaceutical compositions, that comprise such amino acid sequences, proteins and polypeptides; and to uses of such amino acid sequences, proteins and polypeptides.

Serum albumin binding proteins

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.

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De Pinte, Belgium

Peter Schotte