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US010363295B2 (12 ) United States Patent ( 10 ) Patent No. : US 10 , 363, 295 B2 Schoor et al. ( 45 ) Date of Patent: Jul. 30 , 2019 ( 54 ) PEPTIDES AND COMBINATION OF ( 58 ) Field of Classification Search PEPTIDES FOR USE IN IMMUNOTHERAPY ??? . .. A61K 39 /00 AGAINST NHL AND OTHER CANCERS USPC . .. .. .. .. 424 / 1 . 41 See application file for complete search history . (71 ) Applicant: Immatics Biotechnologies GmbH , Tuebingen (DE ) (56 ) References Cited ( 72 ) Inventors : Oliver Schoor , Tuebingen ( DE ) ; Andrea Mahr , Tuebingen (DE ); Toni U . S . PATENT DOCUMENTS Weinschenk , Aichwald (DE ) ; Anita 9 ,023 , 803 B2 5 / 2015 Singh et al. Wiebe , Ruebgarten (DE ) ; Jens 9 , 056 , 069 B2 6 / 2015 Singh et al . Fritsche , Dusslingen (DE ) ; Harpreet 9 , 791, 443 B2 10 / 2017 Weinschenk et al. Singh , Muenchen Schwabing (DE ) 9 ,791 , 444 B2 10 / 2017 Weinschenk et al. 2008/ 0039413 A1 2 / 2008 Morris et al. 2011/ 0257890 A1 10 / 2011 Weinschenk et al. ( 73 ) Assignee: IMMATICS BIOTECHNOLOGIES 2012 /0027684 A12 / 2012 Singh et al. GMBH , Tuebingen (DE ) 2013 / 0096016 A1 4 /2013 Weinschenk et al . 2013/ 0164254 A1* 6 / 2013 Pieczykolan .. CO7K 14 /70575 ( * ) Notice : Subject to any disclaimer, the term of this 424 / 85 . 1 patent is extended or adjusted under 35 2013 /0177525 A1 7 /2013 Singh et al . U . S . C . 154 ( b ) by 0 days . FOREIGN PATENT DOCUMENTS ( 21 ) Appl. No .: 16 / 193 , 334 EP 1589100 Al 10 /2005 WO 0157273 A2 8 / 2001 ( 22 ) Filed : Nov . 16 , 2018 WO 2011037827 A2 3 / 2011 WO 2011 / 128448 A 10 / 2011 (65 ) Prior Publication Data WO 2011/ 151403 Al 12 / 2011 WO 2015 / 150327 A1 10 / 2015 US 2019 /0076514 A1 Mar . 14 , 2019 Wo 2015 / 193359 A2 12 / 2015 Related U . S . Application Data OTHER PUBLICATIONS (63 ) Continuation of application No . 15 / 436 , 385, filed on T . Weinschenk , et al. , “ Integrated Functional Genomics Approach Feb . 17 , 2017 , now Pat. No . 10 , 293 , 036 . for the Design of Patientindividual Antitumor Vaccines ” , Cancer Research , vol . 62 , Oct . 2002 , pp . 5818 - 5827 . Search Report dated Nov . 28 , 2016 . ( 60 ) Provisional application No . 62/ 297 ,495 , filed on Feb . International Search Report issued in counterpart application No. 19 , 2016 . PCT/ EP2017 / 053704 dated Jul. 17, 2017 . (30 ) Foreign Application Priority Data * cited by examiner Feb . 19 , 2016 (GB ) . .. .. .. 1602918 . 3 Primary Examiner — Sean E Aeder (51 ) Int. CI. ( 74 ) Attorney , Agent, or Firm — McBee Moore A61K 39 /00 ( 2006 .01 ) CO7K 14 /47 ( 2006 .01 ) Woodward & Vanik IP , LLC CO7K 14 /705 ( 2006 .01 ) CO7K 14 / 725 ( 2006 . 01 ) (57 ) ABSTRACT CO7K 14 / 74 ( 2006 .01 ) CO7K 16 / 30 ( 2006 .01 ) The present invention relates to peptides , proteins, nucleic C12N 5 /0783 ( 2010 .01 ) acids and cells for use in immunotherapeutic methods . In C12N 15 / 115 ( 2010 .01 ) particular, the present invention relates to the immuno C120 1 /6886 ( 2018 .01 ) therapy of cancer. The present invention furthermore relates GOIN 33 / 574 ( 2006 .01 ) to tumor -associated T -cell peptide epitopes, alone or in (52 ) U . S . CI. combination with other tumor - associated peptides that can CPC . .. .. A61K 39 /0011 ( 2013 .01 ) ; C07K 14 /4748 for example serve as active pharmaceutical ingredients of ( 2013 .01 ) ; CO7K 14 / 705 ( 2013 .01 ) ; COOK vaccine compositions that stimulate anti -tumor immune 14 / 7051 (2013 . 01 ) ; CO7K 14 / 70539 ( 2013 .01 ) ; responses, or to stimulate T cells ex vivo and transfer into CO7K 16 / 30 ( 2013 . 01 ) ; C12N 5 / 0638 patients . Peptides bound to molecules of the major histo ( 2013 .01 ) ; C12N 15 / 115 ( 2013 .01 ) ; C120 compatibility complex (MHC ) , or peptides as such , can also 1 / 6886 ( 2013 .01 ) ; GOIN 33 /57492 ( 2013 .01 ) ; be targets of antibodies, soluble T - cell receptors, and other A61K 2039 /5158 ( 2013 .01 ) ; COZK 2319 / 33 binding molecules. ( 2013 .01 ) ; C12N 2310 / 16 ( 2013 .01 ) ; C12N 2501 / 50 ( 2013 . 01 ) ; C120 2600 / 106 ( 2013 .01 ) ; C12Q 2600 / 156 (2013 . 01 ) ; C12Q 2600/ 158 16 Claims, 22 Drawing Sheets ( 2013 .01 ) Specification includes a Sequence Listing . U . S . Patent Jul. 30 , 2019 Sheet 1 of 22 US 10 , 363, 295 B2 . 18NHL samples . 3adiposetissues,adrenalglands15bloodcellsamplesy12vessels10bonemarrows7brainsen breasts,2cartilageseyes3gallbladders6hearts14kidneys19largeintestines20llvers45lungs&lymph 3pleuras,prostatessalivaryslands5skeletalmuscles11skinssmallintestines12spleensstomachs nades,7nerves3ovaries10pancreasesparathyroidglands1peritoneum5pituitary6placentas . 6testes,2thymithyroidglands9tracheas7ureters&urinarybladders5uteriesophagi . Peptide:LLSGOLPTI(A*02) 305normaltissues SeqIDNO:1 FIG.1A U . S . Patent Jul. 30 , 2019 Sheet 2 of 22 US 10 , 363 ,295 B2 . samples 3adiposetissues,adrenalglands15bloodcellsamples12vessels10bonemarrows7brains8 breasts,2cartilageseyes3gallbladders6hearts14kidneys19largeintestines20livers45lungs8lympha nodes,7nerves3ovaries10pancreasesparathyroidglands1peritoneumSpituitary6placentas ipleuras,3prostates7salivaryglands5skeletalmuscles11skinssmallintestines13spleensstarnacks 6testes,2thymithyroidglanda9tracheas7ureters&urinarybledders5utertesophagi Peptide:VLQGLTFTL(A*02) www 305normaltissues SeqIDNO:5 FIG.1B ) Units Arbitrary ( Presentation Relative U . S . Patent Jul. 30 , 2019 Sheet 3 of 22 US 10 , 363, 295 B2 . M. MMMMM MMMMMM ) LAS. LLLLLLLLLLLLSLLLLLLLLLLLLLL4449193 samples 3diposetissues,iadrenalglands15bloodcellsamples12vessels10bonemarrowsingbrains8 breasts,2cartilageseyes3gallbladders6hearts14kidneys19largeintestines20livers45lunes8lymph nodes,7nervesiovaries10pancreases3parathyroidglands1peritoneum5pituitary6placentas 3pleuras,prostates7salivaryglands5skeletalmuscles11skinsmallintestinesspleensSstomeche Stestes,2thymithyroidglands9tracheas7ureters8urinarybladders5uterte&esophagi Peptide:ILASIFETV(A*02) 305normaltissues SeqIDNO:41 FIG.1C U . S . Patent Jul. 30 , 2019 Sheet 4 of 22 US 10 , 363 ,295 B2 Cancertissues 4cancercelllines,6normaltissues(1lymphnode3spleensstomachIuterus)552braincancersbreast cancer,1cecum6coloncancers&leukocyticleukemia2liver10lung8lymphnodemyeloidcellcancer,3ovariancancersIprostaterectum4skin2stomachurinarybladder cancer,uteruscancers(fromlefttoright) Peptide:NLLEQFILL(A*02) issues . Peptidedetectedon SEQIDNO:248 lines FIG.1D ?????????????? U . S . Patent Jul. 30 , 2019 Sheet 5 of 22 US 10 , 363, 295 B2 "TT444444444 Peptide:LLSEETPSA(A*02) SEQIDNO:2 FIG.1E U . S . Patent Jul. 30 , 2019 Sheet 6 of 22 US 10 , 363, 295 B2 . .1. " 1999999999999999999* . -1. * * * * * Peptide:FLLVOTOIDL(A*02) * SEQIDNO:10 1F.FIG U . S . Patent Jul . 30 , 2019 Sheet 7 of 22 US 10, 363 , 295 B2 - ? . ?? .? FIG.1G ??????? U .S . Patentatent Jul. 30 , 2019 Sheet 8 of 22 US 10 , 363, 295 B2 100% . 02)*HLVPASWKL(APeptide: .ba SEQIDNO:13 FIG.1H U . S . Patent Jul . 30 , 2019 Sheet 9 of 22 US 10, 363 , 295 B2 ???????? Peptide:FLGSFIDHV(A*02) 26NO:IDSEQ FIG.11 U .S . Patentatent Jul. 30 , 2019 Sheet 10 of 22 US 10 , 363 ,295 B2 * * * * * * * 02)ILSTLDVEL*(APeptide: SEQIDNO:30 > FIG.1J IV U . S . Patent Jul. 30 , 2019 ????? ?? J0 zz US 10 , 363, 295 B2 11111111111111111111111111111 . ' , ' , ' ' , ' ' , ' ' . SEQIDNO:36 FIG.1K U . S . Patent JulJul. 3030, , 2019 2019 Sheet 12 of 22 US 10 ,363 ,295 B2 1. 1.2 * 1. 2. M 7 TITUT Peptide:ALLEGVKNV(A*02) SEQIDNO:43 FIG.1L U . S . Patent Jul . 3030 , , 20182019 Sheet 13 of 22 US 10 ,363 ,295 B2 . 02)A*SLDLRPLEV(Peptide: 1. FIG.1M U . S . Patent Jul. 30 , 2019 Sheet 14 of 22 US 10 , 363 ,295 B2 . FIG.1N U . S . Patent Jul. 30 , 2019 Sheet 15 of 22 US 10 ,363 ,295 B2 444444444444444444 SEQIDNO:257 FIG.10 U . S . Patent Jul 30 , 2019 Sheet 16 of 22 US 10 ,363 ,295 B2 ••• Peptide:TVLDGLEFKV(A*02) ? SEQIDNO:259 FIG.1P ?? U . S . Patent Jul. 30 , 2019 Sheet 17 of 22 US 10 ,363 ,295 B2 10NHLsamples min traintenimenterendentemente minimumco minnanhimminman un m melaminankunniambiniadminismamamahandanminumantemammametbeideomonmintenimentdelaminemineamministratieonvanderinwinterme tissue,1adrenalgland5bonemarrowscartilagecolonesophagus2eyes 6arteries,2bloodcellsamplesbralns1heartllvers3lungsveinsIadipose gallbladders,1kidney6lymphnodes4pancreases2peripheralnervespituitary glands,1rectum2salivaryskeletalmusclesskinsmallintestinespleen 1stomach,thyroidgland7tracheasurinarybladderIbreast;5ovariesplacentas wasle Normaltissuesamples(eachsamplerepresentsapoolofseveraldönorsk 1prostate,testisIthymusuterus(fromlefttoright) (Peptide:LLPPPSPAA,SEQIDNO160) domainemain entretenimientointernacionais mimic momento FIG.2A Gene:MIXL1 Expression Relative U . S . Patent Jul. 30 , 2019 Sheet 18 of 22 US 10 ,363 ,295 B2 10VAL*ølets 6arteries,2bloodcellsamplesbralns1heartlivers3lungsvelnsadipose tissue,1adrenalglandÍbonemarrowscartilagecolonesophagus2eyes glands,Irectum2salivarytkeletalmuscles1skinsmallintestinespleen 1stomach,thyroidgland7tracheosurinarybladderbreast5overiesplacentas Normaltissuesaipples(eachsamplerepresentsapoolofseveraldonors): gallbladders,Ikidney6lymphnodes4pancreases2peripheralnervespituitary iprostate,1testisIthymusuterus{fromlefttoright) 1991NO:SEQIDSLNSTTWKV,Peptide:( 2B.FIG Gene:CCR4 U . S . Patent Jul. 30 , 2019 Sheet 19 of 22 US 10 , 363, 295 B2 10NHLsamples Micaila M tissue,1adrenalglandSbonemarrowscartilagecolonesophagus2dyes 6arteries,2bloodcellsamplesbruins1heartlivers3lungsveinsadipose gallbladders,1kidney6lymphnodes4pancreases2peripheralnervespituitary glands,1rectum2salivaryskeletalmusclesskinsmallintestineIspleen 1stomach,Ithyroidgland7tracheasurinarybladderbreast5avariesplacentas Normaltissuesamples(eechsamplerepresentsapoolofseveraldonorsk.
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    Discovery of Novel Functional Centers With Rationally Designed Amino Acid Motifs Aloysius Wong, Xuechen Tian, Chris Gehring, Claudius Marondedze To cite this version: Aloysius Wong, Xuechen Tian, Chris Gehring, Claudius Marondedze. Discovery of Novel Functional Centers With Rationally Designed Amino Acid Motifs. Computational and Structural Biotechnology Journal, Elsevier, 2018, 16, pp.70 - 76. 10.1016/j.csbj.2018.02.007. hal-01851991 HAL Id: hal-01851991 https://hal.archives-ouvertes.fr/hal-01851991 Submitted on 26 May 2020 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Distributed under a Creative Commons Attribution| 4.0 International License Computational and Structural Biotechnology Journal 16 (2018) 70–76 Contents lists available at ScienceDirect journal homepage: www.elsevier.com/locate/csbj Discovery of Novel Functional Centers With Rationally Designed Amino Acid Motifs Aloysius Wong a,⁎, Xuechen Tian a,ChrisGehringb, Claudius Marondedze c a Department of Biology, Wenzhou-Kean University, 88 Daxue Road, Ouhai, Wenzhou, Zhejiang Province
  • ED Bobo Orcid.Org 0000-0002-1558-1704

    ED Bobo Orcid.Org 0000-0002-1558-1704

    Molecular identification and functional characterization of a novel adenylyl cyclase from Glycine max ED Bobo orcid.org 0000-0002-1558-1704 Thesis accepted in fulfilment of the requirements for the degree Doctor of Philosophy in Biology at the North-West University Promoter: Prof O Ruzvidzo Co-supervisor: Dr SS Mlambo Co-supervisor: Dr TD Kawadza Graduation ceremony: July 2020 Student number: 27537730 PREFACE AND ACKNOWLEDMENTS This research work is a ground-breaking discovery in the study of secondary messengers in plants commonly known as cyclic adenosine monophosphate (cAMP) which are important signalling molecules. cAMP synthesis is made possible through the action of adenylyl cyclase (AC) enzymes that are responsible for increasing their concentration in cells. This ground-breaking research focused on cloning and expression of the first ever AC in Glycine max; XP_003529590, gene ID Glyma.07G251000 against a background of only 8 cloned and expressed ACs in higher plants. Five of these are from Arabidopsis thaliana, the other three from Hippaestrum hybridium, Nicotiana tabacum and Zea mays. The goal of the research was to elucidate the functional roles of the novel AC in soybean through molecular and bioinformatic characterisation. A lot of experimental work was covered in the Plant Biotechnology laboratory at the North West University in Mafikeng, South Africa to make this project a success. First and fore-most I would want to express my sincere gratitude to my mentor and promoter Professor Oziniel Ruzvidzo for trusting and believing in me that I had it in me to handle a project of such great magnitude as I was coming from a purely ecological background.
  • A Short Splicing Isoform of HBS1L Links the Cytoplasmic Exosome and SKI Complexes in Humans Katarzyna Kalisiak1,2, Tomasz M

    A Short Splicing Isoform of HBS1L Links the Cytoplasmic Exosome and SKI Complexes in Humans Katarzyna Kalisiak1,2, Tomasz M

    Nucleic Acids Research Advance Access published September 26, 2016 Nucleic Acids Research, 2016 1 doi: 10.1093/nar/gkw862 A short splicing isoform of HBS1L links the cytoplasmic exosome and SKI complexes in humans Katarzyna Kalisiak1,2, Tomasz M. Kulinski´ 1,2,Rafa-l Tomecki1,2, Dominik Cysewski1,2, Zbigniew Pietras1,2,3, Aleksander Chlebowski1,2, Katarzyna Kowalska1,2 and Andrzej Dziembowski1,2,* 1Laboratory of RNA Biology and Functional Genomics, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawinskiego 5a, 02-106 Warsaw, Poland, 2Institute of Genetics and Biotechnology, Faculty of Biology, University of Warsaw, Pawinskiego 5a, 02-106 Warsaw, Poland and 3International Institute of Molecular and Cell Biology in Warsaw, Ks. Trojdena 4, 02-109 Warsaw, Poland Received April 18, 2016; Revised August 25, 2016; Accepted September 20, 2016 Downloaded from ABSTRACT INTRODUCTION The exosome complex is a major eukaryotic exori- Messenger RNA (mRNA) molecules exist largely to pro- duce proteins. Since steady-state mRNA levels are deter- bonuclease that requires the SKI complex for its http://nar.oxfordjournals.org/ activity in the cytoplasm. In yeast, the Ski7 protein mined by the rates of synthesis and decay, cytoplasmic links both complexes, whereas a functional equiva- degradation of mRNA plays a fundamental role in the reg- lent of the Ski7 has remained unknown in the human ulation of gene expression. Multiple enzymes, particularly nucleases, participate in genome. eukaryotic mRNA decay. Nucleases involved in 3 -5 cyto- Proteomic analysis revealed that a previously plasmic mRNA degradation pathways can act individually uncharacterized short splicing isoform of HBS1L (e.g. the DIS3L2 protein) (1,2), or be constituents of mul- (HBS1LV3) is the long-sought factor linking the tisubunit complexes.