HRP20250016T1 - Stanice modificirane himerinim antigenskim receptorima za liječenje raka koji eksprimira cldn6 - Google Patents

Stanice modificirane himerinim antigenskim receptorima za liječenje raka koji eksprimira cldn6 Download PDF

Info

Publication number
HRP20250016T1
HRP20250016T1 HRP20250016TT HRP20250016T HRP20250016T1 HR P20250016 T1 HRP20250016 T1 HR P20250016T1 HR P20250016T T HRP20250016T T HR P20250016TT HR P20250016 T HRP20250016 T HR P20250016T HR P20250016 T1 HRP20250016 T1 HR P20250016T1
Authority
HR
Croatia
Prior art keywords
immune effector
cancer
vector
cell
promoter
Prior art date
Application number
HRP20250016TT
Other languages
English (en)
Croatian (hr)
Inventor
Ugur Sahin
Petra OEHM
Benjamin RENGSTL
Katharina REINHARD
Kristina MICHEL
Original Assignee
Biontech Cell & Gene Therapies Gmbh
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Biontech Cell & Gene Therapies Gmbh filed Critical Biontech Cell & Gene Therapies Gmbh
Publication of HRP20250016T1 publication Critical patent/HRP20250016T1/hr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7088—Compounds having three or more nucleosides or nucleotides
    • A61K31/7105—Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K40/00—Cellular immunotherapy
    • A61K40/10—Cellular immunotherapy characterised by the cell type used
    • A61K40/11—T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K40/00—Cellular immunotherapy
    • A61K40/30—Cellular immunotherapy characterised by the recombinant expression of specific molecules in the cells of the immune system
    • A61K40/31—Chimeric antigen receptors [CAR]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K40/00—Cellular immunotherapy
    • A61K40/40—Cellular immunotherapy characterised by antigens that are targeted or presented by cells of the immune system
    • A61K40/41—Vertebrate antigens
    • A61K40/42—Cancer antigens
    • A61K40/4264—Cancer antigens from embryonic or fetal origin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70503—Immunoglobulin superfamily
    • C07K14/7051—T-cell receptor (TcR)-CD3 complex
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70503—Immunoglobulin superfamily
    • C07K14/70517—CD8
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70578—NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/62—DNA sequences coding for fusion proteins
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
    • C12N15/86—Viral vectors
    • C12N15/867—Retroviral vectors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/58—Medicinal preparations containing antigens or antibodies raising an immune response against a target which is not the antigen used for immunisation
    • A61K2039/585—Medicinal preparations containing antigens or antibodies raising an immune response against a target which is not the antigen used for immunisation wherein the target is cancer
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2121/00—Preparations for use in therapy
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2239/00—Indexing codes associated with cellular immunotherapy of group A61K40/00
    • A61K2239/31—Indexing codes associated with cellular immunotherapy of group A61K40/00 characterized by the route of administration
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2239/00—Indexing codes associated with cellular immunotherapy of group A61K40/00
    • A61K2239/38—Indexing codes associated with cellular immunotherapy of group A61K40/00 characterised by the dose, timing or administration schedule
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
    • C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
    • C07K2317/622—Single chain antibody (scFv)
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
    • C07K2319/02—Fusion polypeptide containing a localisation/targetting motif containing a signal sequence
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
    • C07K2319/03—Fusion polypeptide containing a localisation/targetting motif containing a transmembrane segment
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2510/00—Genetically modified cells

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Immunology (AREA)
  • Zoology (AREA)
  • Biochemistry (AREA)
  • Biomedical Technology (AREA)
  • Biophysics (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Biotechnology (AREA)
  • General Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Wood Science & Technology (AREA)
  • Epidemiology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Cell Biology (AREA)
  • Microbiology (AREA)
  • Physics & Mathematics (AREA)
  • Plant Pathology (AREA)
  • Toxicology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Virology (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Peptides Or Proteins (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
HRP20250016TT 2019-02-08 2020-02-05 Stanice modificirane himerinim antigenskim receptorima za liječenje raka koji eksprimira cldn6 HRP20250016T1 (hr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
EP2019053156 2019-02-08
EP20702482.9A EP3920939B1 (en) 2019-02-08 2020-02-05 Chimeric antigen receptor-modified cells for the treatment of cldn6-expressing cancers
PCT/EP2020/052867 WO2020161186A1 (en) 2019-02-08 2020-02-05 Chimeric antigen receptor-modified cells for the treatment of cldn6-expressing cancers

Publications (1)

Publication Number Publication Date
HRP20250016T1 true HRP20250016T1 (hr) 2025-03-14

Family

ID=69374312

Family Applications (1)

Application Number Title Priority Date Filing Date
HRP20250016TT HRP20250016T1 (hr) 2019-02-08 2020-02-05 Stanice modificirane himerinim antigenskim receptorima za liječenje raka koji eksprimira cldn6

Country Status (26)

Country Link
US (1) US20220184119A1 (enExample)
EP (2) EP3920939B1 (enExample)
JP (2) JP7663500B2 (enExample)
KR (1) KR20210124237A (enExample)
CN (1) CN113727720A (enExample)
AU (1) AU2020217868A1 (enExample)
BR (1) BR112021015429A2 (enExample)
CA (1) CA3129140A1 (enExample)
CL (1) CL2021002067A1 (enExample)
CO (1) CO2021010347A2 (enExample)
CU (1) CU20210067A7 (enExample)
DK (1) DK3920939T3 (enExample)
ES (1) ES3002958T3 (enExample)
FI (1) FI3920939T3 (enExample)
HR (1) HRP20250016T1 (enExample)
HU (1) HUE070174T2 (enExample)
IL (1) IL285122A (enExample)
LT (1) LT3920939T (enExample)
MX (1) MX2021009507A (enExample)
PL (1) PL3920939T3 (enExample)
PT (1) PT3920939T (enExample)
RS (1) RS66364B1 (enExample)
SG (1) SG11202108339TA (enExample)
SI (1) SI3920939T1 (enExample)
SM (1) SMT202500012T1 (enExample)
WO (1) WO2020161186A1 (enExample)

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2021129927A1 (en) * 2019-12-23 2021-07-01 Biontech Cell & Gene Therapies Gmbh Treatment with immune effector cells engineered to express an antigen receptor
KR20240133791A (ko) * 2021-12-09 2024-09-04 비온테크 에스이 Cldn6를 발현하는 암을 치료하기 위한 키메라 항원 수용체 변형 세포
WO2024046572A1 (en) * 2022-09-01 2024-03-07 BioNTech SE Chimeric antigen receptor-modified cells for the treatment of cldn6 expressing cancer
CN114478802B (zh) * 2022-01-28 2023-05-26 郑州大学 一种嵌合抗原受体及其应用
CN114410588B (zh) * 2022-01-29 2022-11-04 西安电子科技大学 一种α1β1整合素依赖增强型CAR巨噬细胞及其制备方法和应用
CN119654342B (zh) * 2022-07-28 2025-07-18 乐普创一生物科技（上海）有限公司 抗MerTK抗体及其用途
KR20250046264A (ko) * 2022-07-29 2025-04-02 레전드 바이오테크 아일랜드 리미티드 클라우딘6 겹합 모이어티 및 이의 용도
WO2024088325A1 (zh) * 2022-10-25 2024-05-02 科济生物医药（上海）有限公司 抗体及其应用
WO2025184170A1 (en) 2024-02-27 2025-09-04 Overt Bio, Inc. Methods and compositions for improving t cell function in an immunosuppressive environment

Family Cites Families (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
HK1047109A1 (zh) 1999-10-15 2003-02-07 University Of Massachusetts 作为指定基因干预工具的rna干预轨迹基因
US6326193B1 (en) 1999-11-05 2001-12-04 Cambria Biosciences, Llc Insect control agent
WO2001096584A2 (en) 2000-06-12 2001-12-20 Akkadix Corporation Materials and methods for the control of nematodes
WO2013143555A1 (en) 2012-03-26 2013-10-03 Biontech Ag Rna formulation for immunotherapy
EP4026909A1 (en) * 2013-12-19 2022-07-13 Novartis AG Human mesothelin chimeric antigen receptors and uses thereof
DK3126381T4 (da) * 2014-04-01 2022-04-04 Biontech Cell&Gene Therapies Gmbh Claudin-6-specifikke immunoreceptorer og t-celleepitoper
MA40921A (fr) * 2014-11-05 2017-09-12 Abbvie Stemcentrx Llc Récepteurs antigéniques chimériques anti-cldn et procédés d'utilisation
CN106146666B (zh) * 2015-03-26 2019-09-06 科济生物医药（上海）有限公司 靶向cldn6的免疫效应细胞及其制备方法和应用
WO2016180467A1 (en) 2015-05-11 2016-11-17 Biontech Cell & Gene Therapies Gmbh Enhancing the effect of car-engineered t cells by means of nucleic acid vaccination
JP7654240B2 (ja) * 2017-09-19 2025-04-01 マサチューセッツ インスティテュート オブ テクノロジー キメラ抗原受容体ｔ細胞治療のための組成物およびその使用
CN109206524B (zh) * 2018-09-25 2022-04-05 山东兴瑞生物科技有限公司 抗Claudin18A2嵌合抗原受体、其修饰的T细胞及T细胞制备方法和用途

Also Published As

Publication number Publication date
AU2020217868A1 (en) 2021-08-12
JP2025060882A (ja) 2025-04-10
ES3002958T3 (en) 2025-03-10
PT3920939T (pt) 2025-01-08
RS66364B1 (sr) 2025-01-31
LT3920939T (lt) 2025-01-10
EP3920939B1 (en) 2024-11-13
CU20210067A7 (es) 2022-03-07
EP4501351A3 (en) 2025-05-07
CO2021010347A2 (es) 2022-01-17
MX2021009507A (es) 2021-09-08
FI3920939T3 (fi) 2025-01-03
PL3920939T3 (pl) 2025-02-17
CA3129140A1 (en) 2020-08-13
CL2021002067A1 (es) 2022-03-11
DK3920939T3 (da) 2025-01-13
HUE070174T2 (hu) 2025-05-28
SI3920939T1 (sl) 2025-03-31
CN113727720A (zh) 2021-11-30
SG11202108339TA (en) 2021-08-30
WO2020161186A1 (en) 2020-08-13
SMT202500012T1 (it) 2025-03-12
BR112021015429A2 (pt) 2021-10-05
KR20210124237A (ko) 2021-10-14
EP3920939A1 (en) 2021-12-15
US20220184119A1 (en) 2022-06-16
JP7663500B2 (ja) 2025-04-16
IL285122A (en) 2021-09-30
EP4501351A2 (en) 2025-02-05
JP2022520059A (ja) 2022-03-28

Similar Documents

Publication Publication Date Title
HRP20250016T1 (hr) Stanice modificirane himerinim antigenskim receptorima za liječenje raka koji eksprimira cldn6
JP7559120B2 (ja) がんに対する免疫療法で使用するための形質移入ｔ細胞およびｔ細胞受容体
CN108884136B (zh) 用于癌症免疫治疗的转染t细胞和t细胞受体
JP2024138280A5 (enExample)
AU2025203355A1 (en) Oncolytic virotherapy and immunotherapy
JP2018500006A5 (enExample)
JP2019511236A5 (enExample)
RS62733B1 (sr) Mnd promoter himernih antigenskih receptora
CN109415687A (zh) 嵌合抗原受体t细胞组合物
JP2017537611A5 (enExample)
EP3298032A1 (en) Anti-ror1 chimeric antigen receptors
Zhu et al. Extensive diversification of MHC in Chinese giant salamanders Andrias davidianus (Anda-MHC) reveals novel splice variants
JP2025060882A5 (enExample)
AU2024201649A1 (en) A fully-human T cell receptor specific for the 369-377 epitope derived from the HER2/Neu (ERBB2) receptor protein
EP3924048A1 (en) Myc, cyclin t1 and/or cdk9 for use in the treatment of degenerative heart and cns disorders
CN118339278A (zh) 用于使胶质祖细胞恢复活力的方法和恢复活力的胶质祖细胞本身
Müllenbach et al. A novel discoidin domain receptor 1 (Ddr1) transcript is expressed in postmeiotic germ cells of the rat testis depending on the major histocompatibility complex haplotype
Ma et al. Comparative transcriptional activity of five promoters in BAC-cloned MDV for the expression of the hemagglutinin gene of H9N2 avian influenza virus
JPWO2019236577A5 (enExample)
Sun et al. Klf4 could be activated by Pou5f3/Stat3 to induce the expression of Nanog in Japanese flounder
US20250257344A1 (en) Method of regulating alternative polyadenylation in rna
Lee et al. Transcriptional regulation of cathelicidin genes in chicken bone marrow cells
Zöller et al. Sequence comparison of avian interferon regulatory factors and identification of the avian CEC-32 cell as a quail cell line
US20220347215A1 (en) SIRPalpha-SILENCED NATURAL KILLER (NK) CELLS
CA3193694A1 (en) T cell receptors directed against bob1 and uses thereof