Patents Assigned to MAX-DELBRÜCK-CENTRUM FÜR MOLEKULARE MEDIZIN IN DER HELMHOLTZ-GEMEINSCHAFT
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Publication number: 20240087677Abstract: A method for analysis of omics data related to samples derived from a human, animal or disease model is disclosed. The method comprises the steps of: a) Determining a plurality of latent spaces by inputting the omics data into a plurality of omics neural networks in parallel and achieving a plurality of latent spaces each comprising a set of latent factors by performing the calculations of the plurality of omics neural networks in a data processing unit, wherein the output of the omics neural networks each provides a respective latent space; b) Consolidating the plurality of latent spaces into one reproducible latent space, wherein the step of consolidating is processed by a data processing unit; wherein the consolidated latent factors represent characteristics of the samples to be analyzed.Type: ApplicationFiled: January 19, 2022Publication date: March 14, 2024Applicant: Max-Delbrück-Centrum für Molekulare Medizin in der Helmholtz-GemeinschaftInventors: Vedran FRANKE, Bora UYAR, Jonathan RONEN, Altuna AKALIN
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Patent number: 11891635Abstract: A method for modifying double stranded DNA (dsDNA) employing an RNA guided DNA endonuclease to generate two double strand breaks in the dsDNA molecule to be modified, and replacement of the sequence positioned between the double strand breaks with a substitute DNA sequence using the non-homologous end joining (NHEJ) pathway, and corresponding kits and compositions for modifying double stranded DNA molecules.Type: GrantFiled: December 21, 2018Date of Patent: February 6, 2024Assignee: Max-Delbrück-Centrum für Molekulare Medizin in der Helmholtz-GemeinschaftInventors: Ralf Kühn, Eric Danner
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Patent number: 11820829Abstract: A nucleic acid molecule encoding an antibody or antibody fragment, wherein the antibody or antibody fragment binds an epitope of the extracellular domain of CD269 (BCMA), a host cell comprising the nucleic acid molecule and a composition comprising the host cell.Type: GrantFiled: October 23, 2020Date of Patent: November 21, 2023Assignee: Max-Delbrück-Centrum für Molekulare Medizin in der Helmholtz-GemeinschaftInventors: Felix Oden, Stephen Marino, Oliver Daumke
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Publication number: 20230287343Abstract: A method for generating a three-dimensional neuromuscular organoid in vitro includes providing a first cell culture that includes disease-specific neuromesodermal progenitor cells, 30% to 90% of which co-express BRACHYURY/SOX2 and 10% to 70% of which co-express TBX6. The disease-specific neuromesodermal progenitor cells are cultivated in a first differentiation medium chosen from the group consisting of i) a non-supplemented serum-free cell culture medium and ii) a serum-free cell culture medium supplemented with at least one of a ROCK inhibitor, an activator of a growth factor signaling pathway, and an activator of an insulin signaling pathway. The first differentiation medium is replaced by a second differentiation medium within 1 to 3 days after cultivation start. The second differentiation medium is replaced by a non-supplemented serum-free cell culture medium within another 1 to 3 days. A three-dimensional neuromuscular organoid is obtained from the non-supplemented serum-free cell culture medium.Type: ApplicationFiled: July 12, 2021Publication date: September 14, 2023Applicant: MAX-DELBRÜCK-CENTRUM FÜR MOLEKULARE MEDIZIN IN DER HELMHOLTZ-GEMEINSCHAFTInventor: Asimina GKOUTI
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Patent number: 11667722Abstract: A composition comprising a cell or a population thereof, wherein the cell comprises a polynucleotide encoding an antibody or a fragment thereof that binds CD269 (BCMA), wherein the binding to CD269 (BCMA) disrupts the interaction between CD269 and its native ligands (BAFF and APRIL). Also disclosed is treatment of plasma cell-mediated diseases such as multiple myeloma and autoimmune diseases.Type: GrantFiled: July 8, 2020Date of Patent: June 6, 2023Assignee: Max-Delbrück-Centrum für Molekulare Medizin in der Helmholtz-GemeinschaftInventors: Martin Lipp, Felix Oden, Uta Höpken, Gerd Müller, Oliver Daumke, Stephen Marino, Daniel Olal
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Patent number: 11401316Abstract: The present invention pertains to novel high avidity antigen recognizing constructs against Human Papilloma Virus antigens. The invention provides novel T cell receptor (TCR) based molecules which are selective and specific for HPV 16/18 proteins E5, E6 and E7. The TCR of the invention, and HPV antigen-binding fragments derived therefrom, are of use for the diagnosis, treatment and prevention of HPV infection, as well as for the diagnosis, treatment and prevention of HPV infection mediated secondary diseases as HPV infection caused cancers, such as cervical, nasopharyngeal or head and neck cancer. Further provided are nucleic acids encoding the proteins of the invention, and recombinant cells expressing the same.Type: GrantFiled: October 13, 2016Date of Patent: August 2, 2022Assignee: MAX-DELBRUECK-CENTRUM FUER MOLEKULARE MEDIZIN IN DER HELMHOLTZ-GEMEINSCHAFTInventors: Thomas Blankenstein, Gerald Willimsky
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Patent number: 11396664Abstract: The invention relates to a system and method for introducing DNA into cells. In particular, the invention relates to a method for introducing single or multiple copies of a DNA sequence or gene of interest into a cell comprising providing: a) a “copy and paste” transposase; and b) a construct comprising a DNA sequence or gene of interest flanked by a “copy and paste” transposon terminal sequence, such as an LTS or RTS. A novel “copy and paste” transposon of the Helitron family is described along with systems for using the corresponding transposase in methods for introducing DNA into cells, for example, to generate cell lines for use in protein production, cell and gene therapy or as reference standards.Type: GrantFiled: February 10, 2017Date of Patent: July 26, 2022Assignees: MAX-DELBRÜCK-CENTRUM FÜR MOLEKULARE MEDIZIN IN DER HELMHOLTZ-GEMEINSCHAFT, GENETIC INFORMATION RESEARCH INSTITUTEInventors: Tilmann Buerckstuemmer, Vladimir Vyacheslavovich Kapitonov, Ivana Grabundzija, Zoltan Ivics
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Patent number: 11384071Abstract: Chemical compounds that are useful as inhibitors of mechanotransduction in the treatment of pain and modulation of touch perception and topical administration of the compounds described herein in the treatment of pain and modulation of touch perception.Type: GrantFiled: December 7, 2017Date of Patent: July 12, 2022Assignee: MAX-DELBRÜCK-CENTRUM FÜR MOLEKULARE MEDIZIN IN DER HELMHOLTZ-GEMEINSCHAFTInventors: Gary Richard Lewin, Kathryn Anne Poole, Christiane Wetzel, Liudmila Lapatsina
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Patent number: 11377636Abstract: An in vitro method for identifying, isolating and/or enriching primate naive pluripotent stem cells, the method including analyzing transcription of a type 7 long terminal repeat (LTR7) nucleic acid sequence of a type H human endogenous retrovirus (HERVH) (LTR7/HERVH-associated transcription), and identifying, isolating and/or enriching primate naive pluripotent stem cells based on LTR7/HERVH-associated transcription, wherein LTR7/HERVH-associated transcription is a marker for primate naive pluripotent stem cells. An isolated in vitro population of primate naive pluripotent stem cells is obtained by the method, wherein in the cells LTR7/HERVH-associated transcription is elevated in comparison to control cells, wherein control cells are primed pluripotent stem cells or differentiated cells.Type: GrantFiled: September 6, 2019Date of Patent: July 5, 2022Assignees: Max-Delbrück-Centrum für Molekulare Medizin in der Helmholtz-Gemeinschaft, UNIVERSITY OF BATHInventors: Jichang Wang, Zsuzsanna Izsvák, Laurence Daniel Hurst
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Publication number: 20220202872Abstract: A method for generating a three-dimensional neuromuscular organoid in vitro is disclosed.Type: ApplicationFiled: July 9, 2021Publication date: June 30, 2022Applicant: MAX-DELBRÜCK-CENTRUM FÜR MOLEKULARE MEDIZIN IN DER HELMHOLTZ-GEMEINSCHAFTInventor: Asimina GKOUTI
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Patent number: 11337909Abstract: A cosmetic method for modulating pigmentation in a subject includes administering a modulator of angiotensin-converting enzyme 2 (ACE2 modulator) to the subject. The ACE2 modulator can be an inhibitor of angiotensin-converting enzyme 2 (ACE2 inhibitor), in which case, the ACE2 inhibitor can be administered to increase pigmentation in the subject. The ACE2 modulator can also be an activator of angiotensin-converting enzyme 2 (ACE2 activator), in which case the ACE2 activator can be administered to decrease pigmentation in the subject. The treatment of inflammatory skin disease can also be achieved by inhibition of angiotensin-converting enzyme 2.Type: GrantFiled: November 29, 2018Date of Patent: May 24, 2022Assignee: MAX-DELBRÜCK-CENTRUM FÜR MOLEKULARE MEDIZIN IN DER HELMHOLTZ-GEMEINSCHAFTInventors: Michael Bader, Fatimunnisa Qadri, Mihail Todiras, Natalia Alenina
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Patent number: 11331290Abstract: A method for inhibiting, reducing and/or reducing the risk of cancer metastasis in a subject, including identifying a subject as in need of inhibiting, reducing and/or reducing the risk of cancer metastasis, by identifying the subject as having a cancer with an elevated or up-regulated level of S100A4 transcription compared to a level in non-oncogenic cells, and administering to the subject a therapeutically effective amount of niclosamide or a niclosamide derivate, thereby inhibiting or reducing S100A4 transcription, so as to inhibit, reduce and/or reduce the risk of cancer metastasis, wherein 15 to 400 mg niclosamide or niclosamide derivate is administered per kg body weight of the subject (mg/kg), 1 or 2 times daily.Type: GrantFiled: January 28, 2020Date of Patent: May 17, 2022Assignee: Max-Delbrück-Centrum für Molekulare Medizin in der Helmholtz-GemeinschaftInventors: Ulrike Stein, Wolfgang Walther, Ulrike Sack, Peter M. Schlag
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Patent number: 11294163Abstract: A microscope-autofocus device for feedback-controlling a focal position of an imaging system of a microscope apparatus, wherein the imaging system includes a microscope objective, a monitoring beam source for creating a monitoring beam, a detector device for detecting a drift variation of an axial objective distance between the microscope objective and a sample by sensing the monitoring beam directed through the imaging system to the sample and reflected by the sample, and a feedback loop device for controlling the imaging system in dependency on the detected objective distance variation of the microscope objective.Type: GrantFiled: October 18, 2018Date of Patent: April 5, 2022Assignee: Max-Delbrück-Centrum für Molekulare Medizin in der Helmholtz-GemeinschaftInventors: Paolo Annibale, Marc Bathe-Peters, Martin Lohse
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Publication number: 20210302442Abstract: The present invention relates to a method for the quantification of seeding (?t50) of an amyloidogenic aggregate, methods for assessing the risk for development, predicting the onset or assessing the progression of a polyQ disease, and a method for identifying compounds that inhibit mHTT seeding activity (HSA) in vitro. Further, uses of fluorophore-bearing polyQ proteins, particularly mutant N-terminal huntingtin fragments comprising exon-1 and related soluble protein constructs are provided.Type: ApplicationFiled: August 7, 2019Publication date: September 30, 2021Applicant: MAX-DELBRÜCK-CENTRUM FÜR MOLEKULARE MEDIZIN IN DER HELMHOLTZ-GEMEINSCHAFTInventors: Anne AST, Alexander BUNTRU, Erich WANKER
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Patent number: 11028084Abstract: A method is for treatment of a disease associated with genotoxic stress-induced inhibitor of nuclear factor-?B kinase/nuclear factor kappa-light chain enhancer of activated B cells (IKK/NF-?B) signaling. The method can include administering a compound to a subject having a cancer exhibiting genotoxic stress induced IKK/NF-?B activation.Type: GrantFiled: November 14, 2017Date of Patent: June 8, 2021Assignees: Max-Delbrück-Centrum für Molekulare Medizin in der Helmholtz-Gemeinschaft, Forschungsverbund Berlin e.VInventors: Claus Scheidereit, Michael Willenbrock, Peter Lindemann, Silke Radetzki, Jens-Peter Von Kries, Marc Nazare
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Patent number: 11001830Abstract: The present invention relates to the field of immunotherapy, in particular, to adoptive T cell therapy, T cell receptor (TCR) gene therapy and vaccination. The invention provides a method for preparing a nucleic acid encoding the TCR alpha chain construct (TRA) and TCR beta chain construct (TRB) of a TCR construct specific for an epitope from an antigen presented on major histocompatibility complex (MHC), comprising contacting T cells isolated from a donor with a library of artificial antigen presenting cells (APC) comprising cells expressing all MHC I or MHC II alleles present in the donor, preferably, in K562 cells. The TCR construct can be expressed in a T cell, which is useful for adoptive T cell therapy, e.g., of cancer, viral infections or autoimmune diseases. The invention further provides a method for identifying the epitope recognized by said TCR. Immunogenic epitopes recognized by said TCRs can be used to develop vaccine formulations to induce antigen-specific T cell immunity in patients.Type: GrantFiled: March 15, 2016Date of Patent: May 11, 2021Assignees: MAX-DELBRÜCK-CENTRUM FÜR MOLEKULARE MEDIZIN IN DER HELMHOLTZ-GEMEINSCHAFT, HELMHOLTZ ZENTRUM MÜNCHEN-DEUTSCHES FORSCHUNGSZENTRUM FÜR GESUNDHEIT UNDInventors: Felix Lorenz, Wolfgang Uckert, Christian Ellinger, Dolores Schendel
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Patent number: 10975136Abstract: The present invention relates to the field of genetic engineering, in particular, to a transposon-based transfection kit suitable for transfection of primary cells, such as T cells, comprising mRNA encoding a transposase, or reagents for generating mRNA encoding said transposase, as well as minicircle DNA comprising the transposon. The invention also relates to a nucleic acid, preferably, a DNA minicircle, comprising a transposon, wherein the transposon encodes a protein and at least one miRNA, wherein the sequences encoding the miRNA are located in an intron and expression of the protein and the miRNA is regulated by the same promoter. The invention also provides a population of cells obtainable with the method of the invention. Methods of transfection are also provided, as well as medical use, e.g. in immunotherapy, in particular, in adoptive T cell therapy or T cell receptor (TCR) or chimeric antigen receptor (CAR) gene therapy.Type: GrantFiled: March 15, 2017Date of Patent: April 13, 2021Assignee: Max-Delbrück-Centrum für Molekulare Medizin in der Helmholtz-GemeinschaftInventors: Wolfgang Uckert, Mario Bunse, Julian Clauss, Zsuzsanna Izsvák
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Publication number: 20210061876Abstract: The present invention pertains to antigen recognizing constructs against tumor specific proteasome splicing variants. The invention in particular provides novel T cell receptor (TCR) based molecules which are selective and specific for tumor cells carrying antigenic epitopes generated by proteasome peptide splicing of tumor specific antigens. The TCRs of the invention, and antigen binding fragments derived therefrom, are of use for the diagnosis, treatment and prevention of proliferative diseases, preferably for the treatment of cancer. Further provided are nucleic acids encoding the antigen recognizing constructs of the invention, vectors comprising these nucleic acids, recombinant cells expressing the antigen recognizing constructs and pharmaceutical compositions comprising the compounds of the invention.Type: ApplicationFiled: January 2, 2019Publication date: March 4, 2021Applicants: Max-Delbrück-Centrum für Molekulare Medizin in der Helmholtz-Gemeinschaft, Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts, Imperial College Innovations Limited, Charité - Universitätsmedizin BerlinInventors: Thomas BLANKENSTEIN, Gerald WILLIMSKY, Juliane LIEPE, Peter Michael KLOETZEL, Michele MISHTO, Christin BEIER
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Patent number: 10851172Abstract: A method of treating a medical disorder associated with the presence of pathogenic B cells expressing B cell maturation antigen (BCMA), the method comprising administering to a subject an isolated antibody or antibody fragment comprising specific VH and VL domain complementary determining region (CDR) sequences, wherein the antibody or fragment thereof specifically binds an epitope of the extracellular domain of CD269 (BCMA).Type: GrantFiled: October 25, 2018Date of Patent: December 1, 2020Assignee: MAX-DELBRÜCK-CENTRUM FÜR MOLEKULARE MEDIZIN IN DER HELMHOLTZ-GEMEINSCHAFTInventors: Felix Oden, Stephen Marino, Oliver Daumke
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Patent number: 10781243Abstract: The present invention relates to the field of immunotherapy, in particular adoptive T cell therapy or T cell receptor (TCR) gene therapy of cancer. The invention provides a nucleic acid encoding at least one T cell receptor alpha chain construct and/or TCR beta chain construct of a TCR construct capable of specifically binding to an epitope from NY-ESO-1 (also designated CTAG-1) in complex with a human MHC, wherein the TCR alpha chain construct and/or the TCR beta chain construct comprises a complementarity determining region 3 (CDR3) having at least 90% sequence identity to an amino acid selected from SEQ ID NO: 1-20. The invention provides TCR constructs restricted to an epitope from NY-ESO-1 presented on MHC I, and, for the first time, TCR constructs restricted to an epitope from NY-ESO-1 presented on MHC II molecules, and thus enables a combined adoptive T cell therapy with both recombinant CD4+ and re-combinant CD8+ T cells.Type: GrantFiled: March 11, 2016Date of Patent: September 22, 2020Assignee: MAX-DELBRÜCK-CENTRUM FÜR MOLEKULARE MEDIZIN IN DER HELMHOLTZ-GEMEINSCHAFTInventors: Thomas Blankenstein, Lucia Poncette, Xiaojing Chen