Abstract: 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)m-(Aax)(NH2)-(Aax)n-B-(Aax)o, or (Aax)m-B-(Aax)n-(Aax)(NH2)-(Aax)o, to a Gln residue comprised in the heavy or light chain of an antibody. Aax(NH2) is an amino acid, amino acid derivative or amino acid mimetic comprising a side chain having a primary amine group.

Abstract: 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)m-(Aax)(NH2)-(Aax)n-B-(Aax)o, or (Aax)m-B-(Aax)n-(Aax)(NH2)-(Aax)o, to a Gln residue comprised in the heavy or light chain of an antibody.

Abstract: Site-specific modification of proteins with microbial transglutaminase (MTG) is a powerful and versatile strategy for a controlled modification of proteins under physiological conditions. We present evidence that solid-phase microbead-immobilization can be 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. We demonstrate that MTG remained firmly immobilized with no detectable column bleeding and that enzyme activity was sustained during continuous operation, which allowed for a convenient recycling of the enzyme, thus going beyond solution-phase MTG conjugation. In addition it is showed that immobilized MTG shows enhanced selectivity towards a certain residue in the presence of several reactive residues which are all targeted if the conjugation was carried out in solution.

Abstract: An alpha radiolabeled gastrin analogue is used in peptide receptor radionuclide therapy (PRRT) applications. In particular, an alpha radiolabeled gastrin analogue, which exhibits excellent biodistribution and therapeutic efficacy while toxicity for healthy tissues is prevented and/or reduced. The alpha radiolabeled gastrin analogue is used in methods of treating cholecystokinin (CCKB) receptor positive diseases.

Abstract: The present invention is directed towards isomerically pure 18F-labelled (6S)- or (6R)-5-methyltetrahydrofolate radiopharmaceuticals, wherein the phenyl group within the folate structure, has been replaced by an 18F-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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

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

Abstract: 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-NH2, 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.

Abstract: Site-specific modification of proteins with microbial transglutaminase (MTG) is a powerful and versatile strategy for a controlled modification of proteins under physiological conditions. We present evidence that solid-phase microbead-immobilization can be 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. We demonstrate that MTG remained firmly immobilized with no detectable column bleeding and that enzyme activity was sustained during continuous operation, which allowed for a convenient recycling of the enzyme, thus going beyond solution-phase MTG conjugation. In addition it is showed that immobilized MTG shows enhanced selectivity towards a certain residue in the presence of several reactive residues which are all targeted if the conjugation was carried out in solution.

Abstract: 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.

Abstract: 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 comprising or having the peptide structure (shown in N->C direction) Gly-(Aax)m-B-(Aax)n via the N-terminal primary amine of the N-terminal glycine (Gly) residue to a glutamine (Gln) residue comprised in the heavy or light chain of an antibody.

Abstract: The present invention provides compounds according to General Formula (1)(i) or (1)(ii): wherein A is a diagnostic or therapeutic agent comprising a binding site for a tumor antigen, and the spacer comprises at least one C—N bond.

Abstract: It is therefore the objective of the present invention to provide minigastrin derivates which further improve the accumulation in CCK-2 receptor positive tumours by simultaneously very low accumulation in other organs, e.g. the kidneys.

Abstract: 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-NH2, 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.

Abstract: 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)m-(Aax)(NH2)-(Aax)n-B-(Aax)o, or (Aax)m-B-(Aax)n-(Aax)(NH2)-(Aax)o, to a Gln residue comprised in the heavy or light chain of an antibody. Aax(NH2) is an amino acid, amino acid derivative or amino acid mimetic comprising a side chain having a primary amine group.

Abstract: The present invention is directed towards new 18F-folate radiopharmaceuticals, wherein the 18F 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.

Abstract: The present invention is directed towards new 18F-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.