Paul Scherrer Institut

Innate Pharma

Merck & Cie

Mallinckrodt, Inc.

Merck Patent Gmbh

Eth Zurich

Universitat Basel

Itm Isotope Technologies Munich Se

Mereck & Cie

Roger Schibli

Rudolf Moser

Viola Groehn

Laurent Gauthier

Christian Belmant

Delphine Bregeon

Eliane Fischer

Patrick Dennler

Martin Behe

Simon Mensah Ametamey

Cristina Magdalena Muller

Roger Alberto

François Romagne

Cindy Ramona Fischer

Cristina Müller

Philipp Rene Spycher

Cristina Magdalena Mueller

François Romagné

Francois Romagne

Konstantin Zhernosekov

Tobias Ludwig Ross

Andre Egli

Viola Vogel

Francois Romagné

Melpomeni Fani

Nicholas Philip Van Der Meulen

Martina Benesova

Cristina Mueller

Silvan Boss

Jori Wehrmuller

Simon Ametamey

Francesca Borgna

Damian Wild

Mamta Chabria

Simon Arnoldini

Samuel Hertig

Christoph Umbricht

Andr&eacute; Egli

Harriet Struthers

Thomas Betzel

Olivier Kreis

David Hurwitz

Alessandra Moscaroli

François Romagnè

Nathalie Grob

Thomas Mindt

Cristina Magdalena MÜLLER

A radiopeptide is provided which comprises (a) a radionuclide, wherein the radionuclide is terbium-161, (b) a chelator coordinating terbium-161, and (c) a peptide or peptide analogue, which is a somatostatin receptor (SSTR) antagonist. The radiopeptide is suitable for use in the treatment of tumor diseases.

[161 tb]-based radiopeptides

The present invention relates to a method for generating an antibody-payload conjugate by means of a microbial transglutaminase (MTG). The method comprises a step of conjugating a linker having a primary amine residue, said linker having the peptide structure (shown in N->C direction) (Aax)-(Aax)(NH)-(Aax)-B-(Aax), or (Aax)-B-(Aax)-(Aax)(NH2)-(Aax), to a Gln residue comprised in the heavy or light chain of an antibody. Aax(NH) is an amino acid, amino acid derivative or amino acid mimetic comprising a side chain having a primary amine group.

Transglutaminase conjugation method and linker

The present invention is directed towards isomerically pureF-labelled (6S)- or (6R)-5-methyltetrahydrofolate radiopharmaceuticals, wherein the phenyl group within the folate structure, has been replaced by anF-labelled N-heterocycle, for use in diagnostic imaging of a cell or population of cells expressing a folate-receptor in vitro or in vivo or for use in monitoring of cancer or inflammatory and autoimmune diseases and therapy thereof.

Isomerically pureF-labelled tetrahydrofolates

The present invention is directed to a composition comprising at least one fibronectin binding polypeptide (FnBP) linked to at least one diagnostic or therapeutic agent, a nucleic acid encoding a fusion polypeptide comprising at least one fibronectin binding polypeptide (FnBP) linked to at least one diagnostic or therapeutic polypeptide agent as well as a corresponding recombinant vector and host cell comprising such a nucleic acid and preferably expressing said fusion polypeptide. The invention also relates to a kit of parts comprising at least one fibronectin binding polypeptide (FnBP), at least one diagnostic or therapeutic agent, and optionally one or more chemical agents for linking the fibronectin binding polypeptide (FnBP) to the diagnostic or therapeutic agent. In addition, the present invention intends said composition, nucleic acid, vector, host cell and kit for use in the therapeutic or prophylactic treatment of a disease, preferably a disease associated with abnormal fibronectin accumulation such as cancer, fibrosis or immune diseases.

Fibronectin-binding peptides for use in tumor or fibrosis diagnosis and therapy

The present invention provides novel compounds that are useful as radiopharmaceuticals, imaging agents and for treatment of cancer.

PSMA-binding agents and uses thereof

A gastrin analogue shows high uptake in CCK-2 receptor positive tumors and simultaneously a very low accumulation in the kidneys. This is achieved by a mini-gastrin analogue PP-F11 having the formula: PP-F11-X-DGlu-DGlu-DGlu-DGlu-DGlu-DGlu-Ala-Tyr-Gly-Trp-Y-Asp-Phe-NH, wherein Y is an amino acid replacing methionine and X is a chemical group attached to the peptide for diagnostic and/or therapeutic intervention at CCK-2 receptor relevant diseases. Very suitable compounds with respect to a high tumor to kidney ratio are mini-gastrin analogues with six D-glutamic acids or six glutamines. These compounds still possess a methionine which can be oxidized easily which is a disadvantage for clinical application under GMP due to the forms which may occur. The elimination of the methionine leads to a lower affinity to oxidation which in general favors the tumor-kidney-ratio. Ideally, the methionine is replaced by norleucine. This PP-F11N mini gastrin exhibits currently the best tumor-kidney-ratio and is the most promising candidate.

Mini-gastrin analogue, in particular for use in CCK2 receptor positive tumour diagnosis and/or treatment

Site-specific modification of proteins with microbial transglutaminase (MTG) is a powerful and versatile strategy for a controlled modification of proteins under physiological conditions. Solid-phase microbead-immobilization is used to site-specifically and efficiently attach different functional molecules important for further downstream applications to proteins of therapeutic relevance including scFV, Fab-fragment and antibodies. MTG remained firmly immobilized with no detectable column bleeding and enzyme activity was sustained during continuous operation. Immobilized MTG shows enhanced selectivity towards a certain residue in the presence of several reactive residues which are all targeted when the conjugation was carried out in solution. The generation of dual site-specifically conjugated IgG1 with immobilized and MTG in solution is reported, i.e. site-specific conjugation to glutamine and lysine residues of IgG1 antibody. Site-specific glutamine conjugation with small peptides containing a lysine residue and a functional moiety is also described.

Site-specific conjugation to antibody lysine residues with solid-phase immobilized microbial transglutaminase MTG and MTG in solution

The present invention is directed towards newF-folate radiopharmaceuticals, wherein theF isotope is linked via a prosthetic group, more specifically via a prosthetic group having a saccharide group, such as a cyclic mono- or oligosaccharide, preferably based on a pyranoside or furanoside, which is covalently linked to the glutamate portion of a folate or derivative thereof, a method of their preparation, as well as their use in diagnosis and monitoring of cancer and inflammatory and autoimmune diseases and therapy thereof.

F-saccharide-folates

The present invention is directed towards newF-folate radiopharmaceuticals, wherein fluorine-18 is covalently linked to the glutamate portion of a folate or derivative thereof, a method of their preparation, as well as their use in diagnosis and monitoring of therapy of cancer and inflammatory and autoimmune diseases.

F-labelled folates as PET radiotracers

The present application relates to methods for the functionalization of immunoglobulins, in particular with drugs. Also disclosed herein are linking reagents, functionalized antibodies, pharmaceutical compositions, and method of treating disease and/or conditions.

Enzymatic conjugation of antibodies

The present application relates to methods for the enzymatic functionalization of immunoglobulins, in particular with drugs. Also disclosed herein are linking reagents, functionalized antibodies, pharmaceutical compositions, and method of treating disease and/or conditions.

Enzymatic conjugation of polypeptides

The present invention is directed towards newF-folate/antifolate analog radiopharmaceuticals, wherein the phenyl group within folate structures has been replaced by anF-heterocycle, their precursors, a method of their preparation, as well as their use in diagnosis of a cell or population of cells expressing a folate-receptor and monitoring of cancer and inflammatory and autoimmune diseases and therapy thereof.

18F-labelled folate/antifolate analogues

The present invention is directed towards newF-folate radiopharmaceuticals, wherein theF isotope F is linked via a prosthetic group, more specifically via a prosthetic group having a saccharide group, such as a cyclic mono- or oligosaccharide, preferably based on a pyranoside or furanoside, which is covalently linked to the glutamate portion of a folate or derivative thereof, a method of their preparation, as well as their use in diagnosis and monitoring of cancer and inflammatory and autoimmune diseases and therapy thereof.

[object Object]

A gastrin analog shows high uptake in CCK-2 receptor positive tumors and simultaneously a very low accumulation in the kidneys. This is achieved by a mini-gastrin analog PP-F11 having the formula: PP-F11-X-DGlu-DGlu-DGlu-DGlu-DGlu-DGlu-Ala-Tyr-Gly-Trp-Y-Asp-Phe-NH, wherein Y is an amino acid replacing methionine and X is a chemical group attached to the peptide for diagnostic and/or therapeutic intervention at CCK-2 receptor relevant diseases. Very suitable compounds with respect to a high tumor to kidney ratio are mini-gastrin analogs with six D-glutamic acids or six glutamines. These compounds still possess a methionine which can be oxidized easily which is a disadvantage for clinical application under GMP due to the forms which may occur. The elimination of the methionine leads to a lower affinity to oxidation which in general favors the tumor-kidney-ratio. Ideally, the methionine is replaced by norleucine. This PP-F11N mini gastrin exhibits currently the best tumor-kidney-ratio and is the most promising candidate.

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Baden, Switzerland

Roger Schibli