Abstract: The present invention relates to biological materials related to c-Met possibly in combination with VEGF and/or EGFR, and more in particular to polypeptides, nucleic acids encoding such polypeptides; to methods for preparing such polypeptides; to host cells expressing or capable of expressing such polypeptides; to compositions and in particular to pharmaceutical compositions that comprise such polypeptides, for prophylactic, therapeutic or diagnostic purposes. Methods and kits for assessing the responsiveness of a patient to c-Met therapy are also described and provided.
Type:
Grant
Filed:
October 1, 2012
Date of Patent:
May 24, 2016
Assignee:
Ablynx N.V.
Inventors:
Gerald Beste, Guy Hermans, Soren Steffensen, Alexander Szyroki, Cedric Jozef Neotere Ververken, Tinneke Denayer
Abstract: In one aspect, the invention relates to a method suitable for administering protein therapeutic molecules orally, sublingually, topically, intravenously, subcutaneously, nasally, vaginally, rectally or by inhalation so as to avoid inactivation, by using VHH polypeptides derived from Camelidae antibodies. The invention further relates to the said therapeutic molecules. The invention further a method for delivering therapeutic molecules to the interior of cells. The invention further relates to anti-IgE therapeutic molecules. In one aspect, the present invention relates to a method wherein an immunoglobulin single variable domain (such as a Nanobody) and/or construct thereof are absorbed in pulmonary tissue. More particularly, the invention provides systemic delivery of an immunoglobulin single variable domain and/or construct thereof via the pulmonary route.
Type:
Grant
Filed:
February 7, 2013
Date of Patent:
April 26, 2016
Assignee:
Ablynx N.V.
Inventors:
Marie-Paule Lucienne Armanda Bouche, Peter Vanlandschoot, Erwin Sablon, Erik Depla, Stefan De Buck, Xavier Saelens, Bert Schepens, Karen Silence, Mark Vaeck, Paul M. P. Van Bergen En Henegouwen, Hans De Haard
Abstract: 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.
Type:
Application
Filed:
May 16, 2014
Publication date:
March 31, 2016
Applicant:
Ablynx N.V.
Inventors:
Yves Meyvis, Veronique De Brabandere, Hans Ulrichts, Ann Brige, Filip Callewaert
Abstract: The present invention relates to amino acid sequences that are directed against/and or that can specifically bind Interleukin-6 Receptor (IL-6R) with improved affinity and/or avidity, and/or that have an improved efficacy and/or potency, and which are capable of (partially, or preferably totally) blocking the IL-6/IL-6R interaction and/or inhibit signalization through IL-6, IL-6R and/or the IL-6/IL-6R complex. The invention further relates to compounds or constructs, and in particular proteins and polypeptides, that comprise or essentially consist of one or more such amino acid sequences.
Type:
Grant
Filed:
March 21, 2014
Date of Patent:
March 1, 2016
Assignee:
Ablynx N.V.
Inventors:
Els Anna Alice Beirnaert, Cedric Jozef Neotere Ververken, Joost Alexander Kolkman, Maarten Van Roy
Abstract: 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.
Type:
Grant
Filed:
August 12, 2013
Date of Patent:
February 23, 2016
Assignee:
Ablynx N.V.
Inventors:
Ann Brige, Christine Labeur, Veronique De Brabandere, Marc Lauwereys
Abstract: The present invention relates to a method for generating immunoglobulin sequences against cell-associated antigens, more particularly, antigens that are membrane-anchored. The invention also provides immunoglobulin sequences obtainable by the method of the invention. Specifically, the present invention relates to the generation of immunoglobulin sequences by use of DNA vaccination. More specifically, the present invention relates to generation of immunoglobulin sequences in camelids, preferably directed against cell-associated antigens, in particular antigens with multiple transmembrane spanning domains, including GPCRs and ion channels, by DNA vaccination. Furthermore, the present invention relates to said immunoglobulin sequences against cell-associated antigens, more particularly, antigens that are membrane-anchored, such as e.g. GPCRs and ion channels, more preferably ion channels.
Type:
Grant
Filed:
December 21, 2009
Date of Patent:
February 16, 2016
Assignee:
Ablynx N.V.
Inventors:
Toon Laeremans, Catelijne Stortelers, Friedrich Nolte, Maria Gonzalez Pajuelo, Joana Assunção, Philippe Van Rompaey
Abstract: The invention relates to a method suitable for administering protein therapeutic molecules orally, sublingually, topically, intravenously, subcutaneously, nasally, vaginally, rectally or by inhalation so as to avoid inactivation, by using VHH polypeptides derived from Camelidae antibodies. The invention further relates to the said therapeutic molecules. The invention further relates to a method for delivering therapeutic molecules to the interior of cells. The invention further relates to polypeptide constructs including VHH directed against EGFR.
Type:
Grant
Filed:
June 19, 2009
Date of Patent:
January 26, 2016
Assignee:
Ablynx N.V.
Inventors:
Karen Silence, Mark Vaeck, Paul M. P. Van Bergen En Henegouwen
Abstract: The invention relates to biparatopic A-beta binding polypeptides and, more specifically, to biparatopic A-beta binding polypeptides comprising at least two immunoglobulin single variable domains binding to different epitopes of A-beta. The invention also relates to specific sequences of such polypeptides, methods of their production, and methods of using them, including methods of treatment of diseases such as Alzheimer's Disease.
Type:
Grant
Filed:
August 29, 2013
Date of Patent:
December 15, 2015
Assignee:
Ablynx N.V.
Inventors:
John E. Park, Cornelia Dorner-Ciossek, Stefan Hoerer, Lothar Kussmaul, Martin Lenter, Katharina Zimmerman, Gerald Beste, Toon Laeremans, Pascal Gerard Merchiers, Jo Vercammen
Abstract: The present invention relates to amino acid sequences that are directed against (as defined herein) G-protein coupled receptors (GPCRs) and in particular to CXCR4 and CXCR7, as well as to compounds or constructs, and in particular proteins and polypeptides, that comprise or essentially consist of one or more such amino acid sequences (also referred to herein as “amino acid sequences of the invention”, “compounds of the invention”, and “polypeptides of the invention”, respectively). Furthermore, the invention provides a new method of making amino acid sequences that are directed against transmembrane protein, and in particular for multiple spanning transmembrane proteins for which the native conformation cannot be reproduced in other “in vitro” system (e.g. GPCRs in general).
Type:
Grant
Filed:
May 18, 2009
Date of Patent:
December 15, 2015
Assignee:
Ablynx N.V.
Inventors:
Christophe Blanchetot, Martine Smit, Regorius Leurs, Sven Jähnichen, Michael John Scott Saunders, Johannes Joseph Wilhelmus De Haard, Peter Vanlandschoot
Abstract: The present invention relates to improved Nanobodies™ against Tumor Necrosis Factor-alpha (TNF-alpha), as well as to polypeptides comprising or essentially consisting of one or more of such Nanobodies. The invention also relates to nucleic acids encoding such Nanobodies and polypeptides; to methods for preparing such Nanobodies and polypeptides; to host cells expressing or capable of expressing such Nanobodies or polypeptides; to compositions comprising such Nanobodies, polypeptides, nucleic acids or host cells; and to uses of such Nanobodies, such polypeptides, such nucleic acids, such host cells or such compositions, in particular for prophylactic, therapeutic or diagnostic purposes, such as the prophylactic, therapeutic or diagnostic purposes.
Abstract: 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).
Abstract: The present invention relates in part to amino acid sequences that are directed against and/or that can specifically bind to an envelope protein of a virus, as well as to compounds or constructs, and in particular proteins and polypeptides, that comprise or essentially consist of one or more such amino acid sequences.
Type:
Grant
Filed:
June 5, 2009
Date of Patent:
November 24, 2015
Assignee:
Ablynx N.V.
Inventors:
Anna Hultberg, Bram Maassen, Peter Vanlandschoot, Erik Depla, Catelijne Stortelers, Cornelis Theodorus Verrips, Steven Van Gucht, Jose Melero, Michael John Scott Saunders, Johannes Joseph Wilhelmus De Haard, Robert Anthony Weiss, Nigel J. Temperton, Xavier Saelens, Bert Schepens, Alexander Szyroki, Michael Marie Harmsen
Abstract: The present invention relates to amino acid sequences that are directed against/and or that can specifically bind Interleukin-6 Receptor (IL-6R) with improved affinity and/or avidity, and/or that have an improved efficacy and/or potency, and which are capable of (partially, or preferably totally) blocking the IL-6/IL-6R interaction and/or inhibit signalization through IL-6, IL-6R and/or the IL-6/IL-6R complex. The invention further relates to compounds or constructs, and in particular proteins and polypeptides, that comprise or essentially consist of one or more such amino acid sequences.
Type:
Grant
Filed:
March 21, 2014
Date of Patent:
November 10, 2015
Assignee:
Ablynx N.V.
Inventors:
Els Anna Alice Beirnaert, Cedric Jozef Neotere Ververken, Joost Alexander Kolkman, Maarten Van Roy
Abstract: The present invention relates to biological materials related to c-Met possibly in combination with VEGF and/or EGFR, and more in particular to polypeptides, nucleic acids encoding such polypeptides; to methods for preparing such polypeptides; to host cells expressing or capable of expressing such polypeptides; to compositions and in particular to pharmaceutical compositions that comprise such polypeptides, for prophylactic, therapeutic or diagnostic purposes. Methods and kits for assessing the responsiveness of a patient to c-Met therapy are also described and provided.
Type:
Application
Filed:
October 1, 2012
Publication date:
October 29, 2015
Applicant:
Ablynx N.V.
Inventors:
Gerald Beste, Guy Hermans, Soren Steffensen, Alexander Szyroki, Cedric Jozef Neotere Ververken, Tinneke Denayer
Abstract: The present invention relates to amino acid sequences that are directed against (as defined herein) human cellular receptors for viruses and/or bacteria such as e.g. Nanobodies specifically recognizing hCD4, hCXCR4, hCCR5, hTLR4, human alphaV integrin, human beta3 integrin, human beta1 integrin, human alpha2 integrin, hCD81, hSR-BI, hClaudin-1, hClaudin-6 and hClaudin-9, as well as to compounds or constructs, and in particular proteins and polypeptides, that comprise or essentially consist of one or more such amino acid sequences. Said amino acid sequences may be used to prevent human cell entry of HIV, HCV, adenoviruses, hantavirus, herpesvirus, echo-virus 1 and others.
Type:
Application
Filed:
February 20, 2015
Publication date:
October 22, 2015
Applicant:
Ablynx N.V.
Inventors:
Christophe Blanchetot, Martine Smit, Regorius Leurs, Sven Jähnichen, Dominique Schols, Michael John Scott Saunders, Johannes Joseph Wilhelmus De Haard, Peter Vanlandschoot, Peter Verheesen
Abstract: The present invention relates to polypeptides comprising at least one single domain antibody directed against vWF, vWF A1 domain, A1 domain of activated vWF, vWF A3 domain, gpIb and/or collagen, homologues of said polypeptides, and/or functional portions of said polypeptides, for the treatment for conditions which require a modulation of platelet-mediated aggregation and which overcomes the problems of the prior art. A further aspect of the invention is methods of production of said polypeptides, methods to coat devices with such polypeptides used in medical procedures (e.g. PCTA, stenting), methods and kits for screening for agents that modulate platelet-mediated aggregation and kits for the diagnosis of diseases related to platelet-mediated aggregation.
Abstract: The present application relates to amino acid sequences that are directed against and/or that can specifically bind to metalloproteinases from the ADAM family, as well as to compounds or constructs, and in particular proteins and polypeptides, that comprise or essentially consist of one or more such amino acid sequences, and to methods of preparing the same.
Type:
Grant
Filed:
December 19, 2007
Date of Patent:
October 13, 2015
Assignee:
Ablynx N.V.
Inventors:
Christophe Blanchetot, Michael John Scott Saunders, Johannes Joseph Wilhelmus De Haard
Abstract: The present invention provides methods for the expression and/or production of variable domains with a C-terminal extension that can be used for coupling of the variable domain to one or more further groups, residues or moieties. In the method of the invention a yield of at least 80% of variable domains with a cysteine containing C-terminal extension is obtained. Also variable domains are provided and polypeptides comprising one or more variable domains obtainable by the methods of the present invention, as well as compounds that comprise such variable domains and/or polypeptides coupled to one or more groups, residues or moieties.
Type:
Grant
Filed:
July 9, 2010
Date of Patent:
October 6, 2015
Assignee:
Ablynx N.V.
Inventors:
Hilde Stals, Veronique De Brabandere, Peter Schotte
Abstract: The present invention relates to amino acid sequences that block the interaction between (a target on) an antigen presenting cell (APC) and (a target on) a T-cell. More particularly, the present invention relates to amino acid sequences that are directed against (as defined herein) a target on an APC (also referred to herein as “APC target”) or a target on a T-cell (also referred to herein as “T-cell target”). The invention further relates to compounds or constructs, and in particular proteins and polypeptides, that comprise or essentially consist of one or more such amino acid sequences.
Type:
Application
Filed:
October 30, 2014
Publication date:
September 24, 2015
Applicant:
Ablynx N.V.
Inventors:
Guy Hermans, Peter Verheesen, Edward Dolk, Hendricus Renerus Jacobus Mattheus Hoogenboom, Michael John Scott Saunders, Hans De Haard, Renee de Bruin
Abstract: The present invention relates to amino acid sequences and Nanobodies that are directed against Epidermal Growth Factor Receptor 2 (HER2), as well as to compounds or constructs, and in particular proteins and polypeptides, that comprise or essentially consist of one or more such amino acid sequences.
Type:
Application
Filed:
January 8, 2015
Publication date:
August 20, 2015
Applicant:
Ablynx N.V.
Inventors:
Hilde Adi Pierrette Revets, Carlo Boutton, Hendricus Renerus Jacobus Mattheus Hoogenboom