IP Library › Granted Patent US 12,552,844
Granted Patent B2
US 12,552,844 · App. 17/624,600 · Granted Feb 17, 2026

De-epitoped alpha gliadin and use of same for the management of celiac disease and gluten sensitivity

Inventors: Yanay Ofran (Tel Aviv, IL); Moshe Ben-David (Rehovot, IL); Assaf Biran (Tel-Aviv, IL); Shiri Zakin (Sde Warburg, IL); Orly Marcu Garber (Modi'in, IL); Anna Chuprin (Tel Aviv, IL)
Assignee: Ukko Inc.
C07K14/415A21D13/066A23L33/185C12N15/8251C12N15/8257
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Quick Facts
Patent No.
US 12,552,844
App. No.
17/624,600
Granted
Feb 17, 2026
Kind
B2
Abstract

A de-epitoped alpha gliadin is provided. Methods of generating same and uses thereof are also provided.

Claims (8)

1 . A de-epitoped alpha gliadin polypeptide mutated compared to the corresponding wild-type gliadin polypeptide, wherein the de-epitoped gliadin polypeptide comprises the amino acid sequence as set forth in any of SEQ ID NOs: 49-58, SEQ ID NOs: 62-79, or SEQ ID NO: 113.

2 . An isolated polynucleotide encoding the de-epitoped alpha gliadin polypeptide of claim 1 .

3 . An expression vector comprising the isolated polynucleotide of claim 2 , operatively linked to a transcriptional regulatory sequence so as to allow expression of said alpha gliadin in a plant cell.

4 . The expression vector of claim 3 , wherein said transcriptional regulatory sequence comprises a plant promoter.

5 . A cell comprising the de-epitoped alpha gliadin polypeptide of claim 1 .

6 . A flour derived from a non-gluten plant, comprising the de-epitoped alpha gliadin polypeptide of claim 1 .

7 . A dough comprising the flour of claim 6 .

8 . A wheat plant genetically modified to express the de-epitoped alpha gliadin polypeptide of claim 1 .

Assignments (2)
SECURITY INTEREST Recorded Nov 22, 2022
From: UKKO INC.
To: VENTURE LENDING & LEASING IX, INC.; WTI FUND X, INC.
Reel/Frame 061858/0281 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 7, 2022
From: OFRAN, YANAY; BEN-DAVID, MOSHE; BIRAN, ASSAF; ZAKIN, SHIRI; MARCU GARBER, ORLY; CHUPRIN, ANNA
To: UKKO INC.
Reel/Frame 059523/0470 →
Continuity (2)
Provisional Application 62870695 · Jul 4, 2019
Related Publication 20220251148A1 · Aug 11, 2022
References Cited (216)
US 3791932A · Schuurs et al. · 1974 [cited by applicant]
US 3839153A · Schuurs et al. · 1974 [cited by applicant]
US 3850578A · Mcconnell · 1974 [cited by applicant]
US 3850752A · Schuurs et al. · 1974 [cited by applicant]
US 3853987A · Dreyer · 1974 [cited by applicant]
US 3867517A · Ling · 1975 [cited by applicant]
US 3879262A · Schuurs et al. · 1975 [cited by applicant]
US 3901654A · Gross · 1975 [cited by applicant]
US 3935074A · Rubenstein et al. · 1976 [cited by applicant]
US 3984533A · Uzgiris · 1976 [cited by applicant]
US 3996345A · Ullman et al. · 1976 [cited by applicant]
US 4034074A · Miles · 1977 [cited by applicant]
US 4098876A · Piasio et al. · 1978 [cited by applicant]
US 4666828A · Gusella · 1987 [cited by applicant]
US 4683202A · Mullis · 1987 [cited by applicant]
US 4801531A · Frossard · 1989 [cited by applicant]
US 4855237A · Morinaga et al. · 1989 [cited by applicant]
US 4879219A · Wands et al. · 1989 [cited by applicant]
US 5011771A · Bellet et al. · 1991 [cited by applicant]
US 5192659A · Simons · 1993 [cited by applicant]
US 5268463A · Jefferson · 1993 [cited by applicant]
US 5272057A · Smulson et al. · 1993 [cited by applicant]
US 5281521A · Trojanowski et al. · 1994 [cited by applicant]
US 5316931A · Donson et al. · 1994 [cited by applicant]
US 5399680A · Zhu et al. · 1995 [cited by applicant]
US 5464764A · Capecchi et al. · 1995 [cited by applicant]
US 5464765A · Coffee et al. · 1995 [cited by applicant]
US 5466785A · de Framond · 1995 [cited by applicant]
US 5487992A · Capecchi et al. · 1996 [cited by applicant]
US 5569597A · Grimsley et al. · 1996 [cited by applicant]
US 5604121A · Hilder et al. · 1997 [cited by applicant]
US 5608142A · Barton et al. · 1997 [cited by applicant]
US 5608144A · Baden et al. · 1997 [cited by applicant]
US 5608149A · Barry et al. · 1997 [cited by applicant]
US 5659026A · Baszczynski et al. · 1997 [cited by applicant]
US 6774279B2 · Dymecki · 2004 [cited by applicant]
US 8021867B2 · Smith et al. · 2011 [cited by applicant]
US 8119381B2 · Smith et al. · 2012 [cited by applicant]
US 8124369B2 · Smith et al. · 2012 [cited by applicant]
US 8129134B2 · Smith et al. · 2012 [cited by applicant]
US 8133697B2 · Smith et al. · 2012 [cited by applicant]
US 8143015B2 · Smith et al. · 2012 [cited by applicant]
US 8143016B2 · Smith et al. · 2012 [cited by applicant]
US 8148098B2 · Smith et al. · 2012 [cited by applicant]
US 8163514B2 · Smith et al. · 2012 [cited by applicant]
US 8304222B1 · Smith et al. · 2012 [cited by applicant]
US 8586526B2 · Gregory et al. · 2013 [cited by applicant]
US 8771945B1 · Zhang · 2014 [cited by applicant]
US 20020019009A1 · Roggen et al. · 2002 [cited by applicant]
US 20030232410A1 · Liljedahl et al. · 2003 [cited by applicant]
US 20050026157A1 · Baltimore et al. · 2005 [cited by applicant]
US 20060014264A1 · Sauer et al. · 2006 [cited by applicant]
US 20060178299A1 · Anderson et al. · 2006 [cited by applicant]
US 20160338366A1 · Elituv et al. · 2016 [cited by applicant]
US 20200124615A1 · Ofran · 2020 [cited by applicant]
JP 6314693B2 · 2018 [cited by applicant]
WO WO1987006261A1 · 1987 [cited by applicant]
WO WO2003104273A2 · 2003 [cited by applicant]
WO WO2005105129A2 · 2005 [cited by examiner]
WO WO2009071334A2 · 2009 [cited by applicant]
WO WO2011146121A1 · 2011 [cited by applicant]
WO WO2011157806A1 · 2011 [cited by applicant]
WO 2013017591A1 · 2013 [cited by applicant]
WO WO2014085593A1 · 2014 [cited by applicant]
WO 2016086185A1 · 2016 [cited by applicant]
WO WO2018122771A1 · 2018 [cited by applicant]
WO WO2020008412A1 · 2020 [cited by applicant]
WO 2021001784A1 · 2021 [cited by applicant]
Mitea, et al., PLoS One 5.12 (2010): e15637 (Year: 2010). [cited by examiner]
Spangler et al (Annu Rev Immunol. Mar. 21, 2015; 33: 139-167) (Year: 2015). [cited by examiner]
Miosge et al (Proc Natl Acad Sci U S A. Sep. 15, 2015;112(37):E5189-98) (Year: 2015). [cited by examiner]
Lee et al (Nat Rev Mol Cell Biol. Dec. 2007;8(12):995-1005) (Year: 2007). [cited by examiner]
Bowie et al. (Science, 1990, 247:1306-1310) (Year: 1990). [cited by examiner]
Burgess et al. (J. Cell Biol. 111:2129-2138, 1990) (Year: 1990). [cited by examiner]
Lazar et al. (Mol. Cell. Biol., 8:1247-1252, 1988) (Year: 1988). [cited by examiner]
Bork (Genome Research, 2000, 10:398-400) (Year: 2000). [cited by examiner]
Kasarda et al (Proceedings of the National Academy of Sciences of the United States of America, vol. 81, No. 15, [Part 1: Biological Sciences] (Aug. 1, 1984), pp. 4712-4716) (Year: 1984). [cited by examiner]
Altschul, S. F. et al. (1990). Basic local alignment search tool. [cited by applicant]
Altschul, S. F. et al. (1997). Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. [cited by applicant]
Anderson. R. P. et al. (2005). T cells in peripheral blood after gluten challenge in coeliac disease. [cited by applicant]
Atreya, C. D. et al. (1992). Site-directed mutations in the potyvirus HC-Pro gene affect helper component activity, virus accumulation, and symptom expression in infected tobacco plants. [cited by applicant]
Ausubel, F. M. (Ed.). (1987). Current protocols in molecular biology. [cited by applicant]
Booth, R. J. et al. (1988). The use of a ‘universal’yeast expression vector to produce an antigenic protein of [cited by applicant]
Brottveit, M. et al. (2011). Assessing possible celiac disease by an HLA-DQ2-gliadin tetramer test. [cited by applicant]
Bui, M. et al. (2009). Simple allele-discriminating PCR for cost-effective and rapid genotyping and mapping. [cited by applicant]
Capecchi, M. R. (1989). Altering the genome by homologous recombination. [cited by applicant]
Carlson, D. F. et al. (2012). Efficient TALEN-mediated gene knockout in livestock. [cited by applicant]
Castelli, F. et al. (2000). Thermoanalytical characterization of high molecular weight glutenin subunits: Water effect on their glass transition. [cited by applicant]
Celis J. E., (Ed.) (2006). Cell Biology: A Laboratory Handbook. 3rd Edition, Institute of Cancer Biology, Danish Cancer Society, vols. I-III, Elsevier Academic Press—Whole Book. [cited by applicant]
Cermak, T. et al. (2011). Efficient design and assembly of custom TALEN and other TAL effector-based constructs for DNA targeting. [cited by applicant]
Certo, M. T. et al. (2012). Coupling endonucleases with DNA end-processing enzymes to drive gene disruption. [cited by applicant]
Chang, P. L. (1995). Somatic gene therapy. [cited by applicant]
Chao, G. et al. (2006). Isolating and engineering human antibodies using yeast surface display. [cited by applicant]
Cho, S. W. et al. (2013). Targeted genome engineering in human cells with the Cas9 RNA-guided endonuclease. [cited by applicant]
Christensen, A. H. et al. (1992). Maize polyubiquitin genes: structure, thermal perturbation of expression and transcript splicing, and promoter activity following transfer to protoplasts by electroporation. [cited by applicant]
Christian, M. et al. (2010). Targeting DNA double-strand breaks with TAL effector nucleases. [cited by applicant]
Chum, P. Y. et al. (2012). Genotyping of plant and animal samples without prior DNA purification. [cited by applicant]
Coligan J.E. (Ed.) (2010). Current Protocols in Immunology. John Wiley & Sons, Inc.—Whole Book. [cited by applicant]
Cong, L. et al. (2013). Multiplex genome engineering using CRISPR/Cas systems. [cited by applicant]
Dahesh, M. et al. (2014). Polymeric assembly of gluten proteins in an aqueous ethanol solvent. [cited by applicant]
Dawson, W. O. et al. (1989). A tobacco mosaic virus-hybrid expresses and loses an added gene. [cited by applicant]
Dicarlo, J. E. et al. (2013). Genome engineering in [cited by applicant]
Egorov, T. A. et al. (1998). Characterisation of high M r wheat glutenin polymers by agarose gel eletrophoresis and dynamic light scattering. [cited by applicant]
Eliezer, D. (2009). Biophysical characterization of intrinsically disordered proteins. [cited by applicant]
Field, J. M. et al. (1987). The structure of a high-M r subunit of durum-wheat ( [cited by applicant]
Foster, G. D. et al. (Eds.). (1998). Plant virology protocols: from virus isolation to transgenic resistance (vol. 81). [cited by applicant]
French, R. et al. (1986). Bacterial gene inserted in an engineered RNA virus: efficient expression in monocotyledonous plant cells. [cited by applicant]
Freshney I. R et al. (Eds.) (2006). Culture of Animal Cells—A Manual of Basic Technique. Fifth Edition, John Wiley & Sons, Inc.—Whole Book. [cited by applicant]
Fromm, M. E. et al. (1986). Stable transformation of maize after gene transfer by electroporation. [cited by applicant]
Gadaleta, A. G. A. T. A. et al. (2008). Stably expressed D-genome-derived HMW glutenin subunit genes transformed into different durum wheat genotypes change dough mixing properties. [cited by applicant]
Gal-On, A. et al. (1992). A zucchini yellow mosaic virus coat protein gene mutation restores aphid transmissibility but has No. effect on multiplication. [cited by applicant]
Gardella, T. J. et al. (1990). Expression of human parathyroid hormone-(1-84) in [cited by applicant]
Gibbs, E. B. et al. (2015). Quantitative biophysical characterization of intrinsically disordered proteins. [cited by applicant]
Gotor, C. et al. (1993). Analysis of three tissue-specific elements from the wheat Cab-1 enhancer. [cited by applicant]
Herman, A. et al. (2007). Incorporating Synthetic Oligonucleotides via Gene Reassembly (ISOR): a versatile tool for generating targeted libraries. [cited by applicant]
Huet, H. et al. (1994). Mutations in the helper component protease gene of zucchini yellow mosaic virus affect its ability to mediate aphid transmissibility. [cited by applicant]
Hwang, W. Y. et al. (2013). Efficient genome editing in zebrafish using a CRISPR-Cas system. [cited by applicant]
Innis, M. A. et al. (Eds.). (1990). PCR protocols: a guide to methods and applications. Academic Press—Whole Book. [cited by applicant]
International Search Report and Written Opinion of the International Searching Authority dated Sep. 30, 2020, issued for the corresponding PCT International Application No. PCT/IB2020/056263, dated Jul. 2, 2020. [cited by applicant]
Ishida, Y. et al. (1996). High efficiency transformation of maize ( [cited by applicant]
Ishida, Y. et al. (2015). Wheat ( [cited by applicant]
Izsvak, Z. et al. (2004). Sleeping beauty transposition: biology and applications for molecular therapy. [cited by applicant]
Jinek, M. et al. (2012). A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. [cited by applicant]
Jinek, M. et al. (2013). RNA-programmed genome editing in human cells. [cited by applicant]
Jo, Y. M. et al. (2017). Cellular localization of wheat high molecular weight glutenin subunits in transgenic rice grain. [cited by applicant]
Karlin, S. et al. (1990). Methods for assessing the statistical significance of molecular sequence features by using general scoring schemes. [cited by applicant]
Karlin, S. et al. (1993). Applications and statistics for multiple high-scoring segments in molecular sequences. [cited by applicant]
Kawakami, K. et al. (2000). Identification of a functional transposase of the Tol2 element, an Ac-like element from the Japanese medaka fish, and its transposition in the zebrafish germ lineage. [cited by applicant]
Kim, Y. G. et al. (1996). Hybrid restriction enzymes: zinc finger fusions to Fok I cleavage domain. [cited by applicant]
Klee, H. et al. (1987). Agrobacterium-mediated plant transformation and its further applications to plant biology. [cited by applicant]
Klein, T. M. et al. (1988). Factors influencing gene delivery into [cited by applicant]
Kooy-Winkelaar, Y. et al. (2011). Gluten-specific T cells cross-react between HLA-DQ8 and the HLA-DQ2α/DQ8β transdimer. [cited by applicant]
Kumar, R. et al. (2002). Human genome search in celiac disease: mutated gliadin T-cell-like epitope in two human proteins promotes T-cell activation. [cited by applicant]
Kurihara, Y. et al. (2003). Cross-protection in [cited by applicant]
Kwon, H. B. et al. (1994). Identification of a light-responsive region of the nuclear gene encoding the B subunit of chloroplast glyceraldehyde 3-phosphate dehydrogenase from [cited by applicant]
Lanio, T. et al. (2000). Automated purification of His6-tagged proteins allows exhaustive screening of libraries generated by random mutagenesis. [cited by applicant]
Last, D. I. et al. (1991). pEmu: an improved promoter for gene expression in cereal cells. [cited by applicant]
Lee, H. J. et al.(2010). Targeted chromosomal deletions in human cells using zinc finger nucleases. [cited by applicant]
Li, T. et al. (2011). TAL nucleases (TALNs): hybrid proteins composed of TAL effectors and FokI DNA-cleavage domain. [cited by applicant]
Liang, Z. et al. (2018). Genome editing of bread wheat using biolistic delivery of CRISPR/Cas9 in vitro transcripts or ribonucleoproteins. [cited by applicant]
Liang, Z. et al. (2018). Genotyping genome-edited mutations in plants using CRISPR ribonucleoprotein complexes. [cited by applicant]
McCabe, D. E. et al. (1988). Stable transformation of soybean ( [cited by applicant]
Mahfouz, M. M. et al. (2011). De novo-engineered transcription activator-like effector(TALE) hybrid nuclease with novel DNA binding specificity creates double-strand breaks. [cited by applicant]
Mali, P. et al. (2013). CAS9 transcriptional activators for target specificity screening and paired nickases for cooperative genome engineering. [cited by applicant]
Maramorosch, K. et al (Eds.) (1984). Methods in Virology: vol. 8. Academic Press—Whole Book. [cited by applicant]
Matsuoka, M. et al. (1993). Tissue-specific light-regulated expression directed by the promoter of a C4 gene, maize pyruvate, orthophosphate dikinase, in a C3 plant, rice. [cited by applicant]
McElroy, D. et al. (1990). Isolation of an efficient actin promoter for use in rice transformation. [cited by applicant]
Menke, D. B. (2013). Engineering subtle targeted mutations into the mouse genome. [cited by applicant]
Miller, J. C. et al. (2011). A TALE nuclease architecture for efficient genome editing. [cited by applicant]
Miskey, C. et al. (2003). The Frog Prince: a reconstructed transposon from Rana pipiens with high transpositional activity in vertebrate cells. [cited by applicant]
Mitea, C. et al. (2010). A universal approach to eliminate antigenic properties of alpha-gliadin peptides in celiac disease. [cited by applicant]
Molberg, O. et al. (1997). Gliadin specific, HLA DQ2-restricted T cells are commonly found in small intestinal biopsies from coeliac disease patients, but not from controls. [cited by applicant]
Neuhaus, G. et al. (1987). Transgenic rapeseed plants obtained by the microinjection of DNA into microspore-derived embryoids. [cited by applicant]
Neuhaus, G. et al. (1990). Plant transformation by microinjection techniques. [cited by applicant]
Ni, M. et al. (1995). Strength and tissue specificity of chimeric promoters derived from the octopine and mannopine synthase genes. [cited by applicant]
Odell, J. T. et al. (1985). Identification of DNA sequences required for activity of the cauliflower mosaic virus 35S promoter. [cited by applicant]
Ohta, Y. (1986). High-efficiency genetic transformation of maize by a mixture of pollen and exogenous DNA. [cited by applicant]
Orozco, B. M. et al. (1993). Localization of light-inducible and tissue-specific regions of the spinach ribulose bisphosphate carboxylase/oxygenase (rubisco) activase promoter in transgenic tobacco plants. [cited by applicant]
Ozuna Serafini, C. V. et al. (2015). Diversification of the celiac disease α-gliadin complex in wheat: A 33-mer peptide with six overlapping epitopes, evolved following polyploidization. [cited by applicant]
Patrascu, L. et al. (2017). Effect of gluten, egg and soy proteins on the rheological and thermo-mechanical properties of wholegrain rice flour. [cited by applicant]
Petersen, J. et al. (2014). T-cell receptor recognition of HLA-DQ2-gliadin complexes associated with celiac disease. [cited by applicant]
Popineau, Y. et al. (2001). Prolamin aggregation, gluten viscoelasticity, and mixing properties of transgenic wheat lines expressing 1Ax and 1Dx high molecular weight glutenin subunit transgenes. [cited by applicant]
Potrykus, I. (1991). Gene transfer to plants: assessment of published approaches and results. [cited by applicant]
Qiao. S. W. et al. (2011). Posttranslational modification of gluten shapes TCR usage in celiac disease. [cited by applicant]
Qu, L. Q. et al. (2008). Expression pattern and activity of six glutelin gene promoters in transgenic rice. [cited by applicant]
Raki, M. et al. (2007). Tetramer visualization of gut-homing gluten-specific T cells in the peripheral blood of celiac disease patients. [cited by applicant]
Reyon, D. et al. (2012). FLASH assembly of TALENs for high-throughput genome editing. [cited by applicant]
Rooke, L. et al. (1999). Overexpression of a gluten protein in transgenic wheat results in greatly increased dough strength. [cited by applicant]
Ruiz-Carnicer, A. et al. (2019). Celiac immunogenic potential of α-gliadin epitope variants from [cited by applicant]
Sambrook, J. et al. (1989). Molecular cloning: a laboratory manual (No. Ed. 2). Cold spring harbor laboratory press. Whole Book. [cited by applicant]
Sanchez-Leon, S. et al. (2018). Low-gluten, nontransgenic wheat engineered with CRISPR/Cas9. [cited by applicant]
Santiago, Y. et al. (2008). Targeted gene knockout in mammalian cells by using engineered zinc-finger nucleases. [cited by applicant]
Shewry, P. R. et al. (2016). Improving wheat to remove coeliac epitopes but retain functionality. [cited by applicant]
Shimamoto, K. et al. (1989). Fertile transgenic rice plants regenerated from transformed protoplasts. [cited by applicant]
Sidney, J. et al. (2013). Measurement of MHC/peptide interactions by gel filtration or monoclonal antibody capture. [cited by applicant]
Smirnova, O. G. et al. (2012). Wheat promoter sequences for transgene expression. [cited by applicant]
Sollid, L. M. et al. (2012). Nomenclature and listing of celiac disease relevant gluten T-cell epitopes restricted by HLA-DQ molecules. [cited by applicant]
Srinivasan, B. et al. (2015). Usefulness of recombinant γ-gliadin 1 for identifying patients with celiac disease and monitoring adherence to a gluten-free diet. [cited by applicant]
Takamatsu, N. et al. (1987). Expression of bacterial chloramphenicol acetyltransferase gene in tobacco plants mediated by TMV-RNA. [cited by applicant]
Takamatsu, N. et al. (1990). Production of enkephalin in tobacco protoplasts using tobacco mosaic virus RNA vector. [cited by applicant]
Tatham, A. S. et al. (1985). The conformation of wheat gluten proteins. The secondary structures and thermal stabilities of α-, β-, γ-and ω-gliadins. [cited by applicant]
Thomson, N. H. et al. (1999). Small angle X-ray scattering of wheat seed-storage proteins: α-, γ-and ω-gliadins and the high molecular weight (HMW) subunits of glutenin. [cited by applicant]
Tonikian, R. et al. (2007). Identifying specificity profiles for peptide recognition modules from phage-displayed peptide libraries. [cited by applicant]
Toriyama, K. et al. (1988). Transgenic rice plants after direct gene transfer into protoplasts. [cited by applicant]
Urnov, F. D. et al. (2005). Highly efficient endogenous human gene correction using designed zinc-finger nucleases. [cited by applicant]
Van Den Broeck, H. C. et al. (2009). Removing celiac disease-related gluten proteins from bread wheat while retaining technological properties: a study with Chinese Spring deletion lines. [cited by applicant]
Van Herpen, T. W. et al. (2006). Alpha-gliadin genes from the A, B, and D genomes of wheat contain different sets of celiac disease epitopes. [cited by applicant]
Walkey, D. G. (1991). Applied plant virology. [cited by applicant]
Watson et al. (1992). Recombinant DNA, 2nd Edition, Scientific American Books, New York—Whole Book. [cited by applicant]
Wilson, M. H. et al. (2007). PiggyBac transposon-mediated gene transfer in human cells. [cited by applicant]
Yamamoto, N. et al. (1994). The promoter of a pine photosynthetic gene allows expression of a β-glucuronidase reporter gene in transgenic rice plants in a light-independent but tissue-specific manner. [cited by applicant]
Yamamoto, Y. Y et al. (1997). Light-responsive elements of the tobacco PSI-D gene are located both upstream and within the transcribed region. [cited by applicant]
Zhang, H. M. et al. (1988). Transgenic rice plants produced by electroporation-mediated plasmid uptake into protoplasts. [cited by applicant]
Zhang, F. et al. (2011). Efficient construction of sequence-specific TAL effectors for modulating mammalian transcription. [cited by applicant]
Broekman et al. “IgE-the main player of food allergy” Drug Discovery Today: Disease Models. Dec. 1, 2015; 17:37-44. [cited by applicant]
Burkovitz et al. “Computational identification of antigen-binding antibody fragments” The Journal of Immunology. Mar. 1, 2013;190(5):2327-34. [cited by applicant]
Burkovitz et al. “Large-scale analysis of somatic hypermutations in antibodies reveals which structural regions, positions and amino acids are modified to improve affinity” The FEBS journal. Jan. 2014;281(1):306-19. [cited by applicant]
Carlson et al. “Targeting DNA with fingers and TALENs” Molecular therapy Nucleic acids. Jan. 1, 2012;1. [cited by applicant]
Cong et al. “Genome engineering using CRISPR-Cas9 system” in Chromosomal mutagenesis Nov. 3, 2014 (pp. 197-217). New York, NY: Springer New York. [cited by applicant]
Fu et al. “Identification of allergenic epitopes and critical amino acids of major allergens in Chinese shrimp ( [cited by applicant]
Hwang et al. “Efficient in vivo genome editing using RNA-guided nucleases” Nature biotechnology. Jan. 29, 2013;31(3):227. [cited by applicant]
Hwang et al. “Heritable and precise zebrafish genome editing using a CRISPR-Cas system” PloS one. Jul. 9, 2013;8(7):e68708. [cited by applicant]
International Search Report issued for PCT Application No. PCT/IB2017/0058470 Dated Apr. 11, 2018. [cited by applicant]
International Search Report issued for PCT Application No. PCT/IB2019/055724 Dated Sep. 26, 2019. [cited by applicant]
Kim et al. “Analysis of targeted chromosomal deletions induced by zinc finger nucleases” Cold Spring Harbor Protocols. Aug. 1, 2010;2010(8):pdb-rot5477. [cited by applicant]
Konig F. “Adverse effects of wheat gluten” Annals of Nutrition and Metabolism. Nov. 1, 2015;67(Suppl. 2):7-14. [cited by applicant]
Kunik et al. “Paratome: an online tool for systematic identification of antigen-binding regions in antibodies based on sequence or structure” Nucleic acids research. Jul. 1, 2012;40(W1):W521-4. [cited by applicant]
Kunik et al. “Structural consensus among antibodies defines the antigen binding site” PLoS computational biology. Feb. 23, 2012;8(2):e1002388. [cited by applicant]
Li et al. “In vivo genome editing restores haemostasis in a mouse model of haemophilia” Nature. Jul. 14, 2011;475(7355):217-21. [cited by applicant]
Li et al. “Modularly assembled designer TAL effector nucleases for targeted gene knockout and gene replacement in eukaryotes” Nucleic acids research. Aug. 1, 2011;39(14):6315-25. [cited by applicant]
Mali et al. “RNA-guided human genome engineering via Cas9” Science. Feb. 15, 2013;339(6121):823-6. [cited by applicant]
Matsuo et al. “Common food allergens and their IgE-binding epitopes” Allergology International. 2015;64(4):332-43. [cited by applicant]
Rubinstein et al. “A machine-learning approach for predicting B-cell epitopes” Molecular immunology. Feb. 1, 2009;46(5):840-7. [cited by applicant]
Sela-Culang et al. “PEASE: predicting B-cell epitopes utilizing antibody sequence” Bioinformatics. Apr. 15, 2015;31(8):1313-5. [cited by applicant]
Sela-Culang et al. “Using a combined computational-experimental approach to predict antibody-specific B cell epitopes” Structure. Apr. 8, 2014;22(4):646-57. [cited by applicant]
Thalhamer et al. “Designing hypoallergenic derivatives for allergy treatment by means of in silico mutation and screening” Journal of allergy and clinical immunology. Apr. 1, 2010;125(4):926-34. [cited by applicant]