A TRANSGLUTAMINE TAG FOR EFFICIENT SITE-SPECIFIC BIOCONJUGATION

Publication number: 20190194344

Abstract: The present invention provides novel peptide sequences for use in microbial transgluatminase-mediated, in particular mTG2-mediated bioconjugations, in particular for the manufacture of antibody-drug-conjugates. Further disclosed are bioconjugation methods employing mTG2 and the novel peptide sequence motifs of the invention. The present invention further provides proteins comprising the novel sequence motifs of the invention as well as polynucleotides encoding the same.

Type: Application

Filed: August 4, 2016

Publication date: June 27, 2019

Applicant: Merck Patent GmbH

Inventors: Birgit Piater, Ulrich Betz, Harald Kolmar, Vanessa Siegmund

METHODS FOR GENERATING BISPECIFIC SHARK VARIABLE ANTIBODY DOMAINS AND USE THEREOF

Publication number: 20180171020

Abstract: The present invention provides a method for generating bispecific shark variable antibody domains (vNAR domains) and uses thereof. The present invention further provides fusion proteins comprising the inventive bispecific vNAR domains as well as polynucleotide libraries for use in the generation of the inventive bi-specific vNARs. Furthermore, the invention provides pharmaceutical compositions comprising the inventive bispecific vNARs or fusion proteins comprising bi-specific vNAR domains for use in the treatment of pathological conditions in an individual. The invention also provides kits of parts comprising the bispecific vNAR domains or fusion proteins.

Type: Application

Filed: October 21, 2015

Publication date: June 21, 2018

Applicant: Merck Patent GmbH

Inventors: Stefan Becker, Bjoern Hock, Stefan Zielonka, Harald Kolmar, Martin Empting

General strategy for antibody library screening

Patent number: 9733240

Abstract: A generally applicable method for the selective covalent attachment of a reporter molecule to a replicating entity that allows one to obtain specific binders from a single round of library screening is disclosed. For example, selective biotinylation of phage particles and yeast cells displaying a binder to any given target can be achieved via application of a coupled enzyme reaction that includes a peroxidase, an oxidase and a catalase.

Type: Grant

Filed: December 14, 2012

Date of Patent: August 15, 2017

Assignee: Merck Patents GmbH

Inventors: Stefan Becker, Tim Heiseler, Alexander Maass, Harald Kolmar

METHOD FOR PEPTIDE SYNTHESIS AND APPARATUS FOR CARRYING OUT A METHOD FOR SOLID PHASE SYNTHESIS OF PEPTIDES

Publication number: 20170218010

Abstract: The invention relates to a method for peptide synthesis, wherein said method comprises the steps of reacting a first amino acid or a first peptide with an ?-amine protected second amino acid in a solvent selected from the group consisting of water, alcohol, and a mixture of water and alcohol, and removing the ?-amine protecting group with a deprotecting solution. The invention further relates to protective agents, their use and an apparatus for carrying out a method for solid phase synthesis of peptides.

Type: Application

Filed: September 29, 2015

Publication date: August 3, 2017

Inventors: Sascha KNAUER, Tobias Michael Louis ROESE, Olga AVRUTINA, Harald KOLMAR, Christina UTH

POTENT INHIBITORS OF HUMAN MATRIPTASE DERIVED FROM MCOTI-II VARIANTS

Publication number: 20160194380

Abstract: The present invention pertains to highly potent Matriptase inhibitors derived from the miniprotein McotI-II.

Type: Application

Filed: April 8, 2014

Publication date: July 7, 2016

Applicant: Merck Patent GmbH

Inventors: Michael TOMASZOWSKY, Niklas WEBER, Bernhard GLOTZBACH, Harald KOLMAR, Bjoern HOCK

HIGH-AFFINITY MATRIPTASE INHIBITORS

Publication number: 20160016998

Abstract: The present invention relates to novel matriptase inhibitors.

Type: Application

Filed: January 9, 2014

Publication date: January 21, 2016

Applicant: Merck Patent GmbH

Inventor: Harald KOLMAR

GENERAL STRATEGY FOR ANTIBODY LIBRARY SCREENING

Publication number: 20140357514

Abstract: A generally applicable method for the selective covalent attachment of a reporter molecule to a replicating entity that allows one to obtain specific binders from a single round of library screening is disclosed. For example, selective biotinylation of phage particles and yeast cells displaying a binder to any given target can be achieved via application of a coupled enzyme reaction that includes a peroxidase, an oxidase and a catalase.

Type: Application

Filed: December 14, 2012

Publication date: December 4, 2014

Inventors: Stefan Becker, Tim Heiseler, Alexander Maass, Harald Kolmar

Use of microproteins as tryptase inhibitors

Patent number: 8278262

Abstract: Disclosed are uses of microproteins preferably microproteins forming a cystine knot (i.e. belonging to the family of inhibitor cystine knot (ICK) polypeptides) or polynucleotides encoding said microproteins for the preparation of a pharmaceutical composition for treating or preventing a disease that can be treated or prevented by inhibiting the activity of tryptase as well as corresponding methods of treatment. Also disclosed are uses of the microproteins for inhibiting tryptase activity, for purifying tryptase, as a carrier molecule for tryptase and for deleting or quantifying tryptase in a sample, including corresponding diagnostic applications. Furthermore disclosed are fusion proteins comprising an inactive barnase as well as fusion proteins comprising barnase and a microprotein. Also encompassed are nucleic acid molecules encoding such a fusion protein, as well as corresponding vectors, host cells, preparation methods and uses of the fusion protein.

Type: Grant

Filed: September 19, 2005

Date of Patent: October 2, 2012

Assignee: BioNTech AG

Inventors: Harald Kolmar, Christian Sommerhoff, Alexander Wentzel

Dimeric or multimeric microproteins

Patent number: 8258258

Abstract: Disclosed is a polypeptide comprising at least two microproteins, which preferably comprise an amino acid sequence having a specific binding activity to a target protein. Furthermore, disclosed are polynucleotides encoding such a polypeptide as well as pharmaceutical compositions and kits comprising said polypeptide or polynucleotide. Also disclosed herein are methods of treatments and second medical uses applying the disclosed polypeptide or polynucleotide. Additionally, the disclosure of the present application relates to a method for forming a covalent bond in a microprotein which can be used for producing the disclosed polypeptides.

Type: Grant

Filed: March 9, 2006

Date of Patent: September 4, 2012

Assignee: BioNTech AG

Inventors: Harald Kolmar, Ernst Boehnlein, Alexander Wentzel, Hans-Ulrich Schmoldt

Polypeptide comprising a knottin protein moiety

Publication number: 20100267610

Abstract: A polypeptide, with an amino acid sequence different from that of knottin protein, having a scaffold moiety with a helix moiety inserted in the scaffold moiety is described. The scaffold moiety comprises a knottin protein, or a fragment of knottin protein.

Type: Application

Filed: February 18, 2008

Publication date: October 21, 2010

Applicant: BIONTECH AG

Inventors: Michael Blind, Harald Kolmar

Dimeric or Multimeric Microproteins

Publication number: 20090156476

Abstract: Disclosed is a polypeptide comprising at least two microproteins, which preferably comprise an amino acid sequence having a specific binding activity to a target protein. Furthermore, disclosed are polynucleotides encoding such a polypeptide as well as pharmaceutical compositions and kits comprising said polypeptide or polynucleotide. Also disclosed herein are methods of treatments and second medical uses applying the disclosed polypeptide or polynucleotide. Additionally, the disclosure of the present application relates to a method for forming a covalent bond in a microprotein which can be used for producing the disclosed polypeptides.

Type: Application

Filed: March 9, 2006

Publication date: June 18, 2009

Applicant: NascaCell Technologies AG

Inventors: Harald Kolmar, Ernst Boehnlein, Alexander Wentzel, Hans-Ulrich Schmoldt

Use of microproteins as tryptase

Publication number: 20090130692

Abstract: Disclosed are uses of microproteins preferably microproteins forming a cystine knot (i.e. belonging to the family of inhibitor cystine knot (ICK) polypeptides) or polynucleotides encoding said microproteins for the preparation of a pharmaceutical composition for treating or preventing a disease that can be treated or prevented by inhibiting the activity of tryptase as well as corresponding methods of treatment. Also disclosed are uses of the microproteins for inhibiting tryptase activity, for purifying tryptase, as a carrier molecule for tryptase and for deleting or quantifying tryptase in a sample, including corresponding diagnostic applications. Furthermore disclosed are fusion proteins comprising an inactive barnase as well as fusion proteins comprising barnase and a microprotein. Also encompassed are nucleic acid molecules encoding such a fusion protein, as well as corresponding vectors, host cells, preparation methods and uses of the fusion protein.

Type: Application

Filed: September 19, 2005

Publication date: May 21, 2009

Applicant: Nasca Cell Technologies AG

Inventors: Harald Kolmar, Christian Sommerhoff, Alexander Wentzel

Method for exposing peptides and polypeptides on the cell surface of bacteria

Patent number: 7186524

Abstract: The inventive method allows peptides or polypeptides to be exposed on the surface of gram-negative host bacteria using specific intimin-based anchor modules. Intimins with shortened carboxy terminals have been found to be particularly suitable anchor modules for passenger domains in the exterior E. coli cell membrane. According to the method, host bacteria are transformed using vectors, on which are located a fused nucleic acid sequence consisting of a sequence segment which codes for an intimin with a shortened carboxy terminal and a nucleic acid sequence segment which codes for the passenger peptide that is to be exposed. The invention permits a particularly large number of passenger domains to be exposed on the cell surface of the bacteria, without adversely affecting the viability of the bacteria.

Type: Grant

Filed: October 25, 2001

Date of Patent: March 6, 2007

Assignee: NascaCell Technologies AG

Inventors: Harald Kolmar, Andreas Christmann, Alexander Wentzel

Method for exposing peptides and polypeptides on the cell surface of bacteria

Publication number: 20040106118

Abstract: The inventive method allows peptides or polypeptides to be exposed on the surface of gram-negative host bacteria using specific intimin-based anchor modules. Intimins with shortened carboxy terminals have been found to be particularly suitable anchor modules for passenger domains in the exterior E.coli cell membrane. According to said method, host bacteria are transformed using vectors, on which are located a fused nucleic acid sequence consisting of a sequence segment which codes for an intimin with a shortened carboxy terminal and a nucleic acid sequence segment which codes for the passenger peptide that is to be exposed. The invention permits a particularly large number of passenger domains to be exposed on the cell surface of the bacteria, without adversely affecting the viability of the bacteria.

Type: Application

Filed: October 15, 2003

Publication date: June 3, 2004

Inventors: Harald Kolmar, Andreas Christmann, Alexander Wentzel

Vectors for the genetic selection of ligand binding proteins in microorganisms by means of signal transduction

Patent number: 5882924

Abstract: The invention relates to a process for the genetic selection in microorganisms of proteins which are capable of ligand binding, in which process a protein which is capable of ligand binding is presented extracytoplasmically and the signal of the ligand binding is passed on by signal transduction to the biosynthetic machinery of the micoorganism for the purpose of expressing a detectable and/or selectable function. In addition to this, the patent discloses microorganisms which are suitable for use in this process, as well as replicons and processes for their preparation.

Type: Grant

Filed: October 22, 1997

Date of Patent: March 16, 1999

Assignee: Behringwerke Aktiengesellschaft

Inventors: Hans-Joachim Fritz, Frank Hennecke, Harald Kolmar