IP Library › Granted Patent US 12,350,349
Granted Patent B2
US 12,350,349 · App. 16/322,803 · Granted Jul 8, 2025

Gene editing of CAR-T cells for the treatment of T cell malignancies with chimeric antigen receptors

Inventors: John F. DiPersio (St. Louis, MO); Matthew Cooper (St. Louis, MO)
Assignee: Washington University
A61K48/0066A61K40/11A61K40/22A61K40/31A61K40/418A61K40/421A61K40/4211A61K48/0008A61K48/0058A61K48/0091A61P35/02A61P37/06C12N5/0636A61K2239/31A61K2239/38A61K2239/48
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Quick Facts
Patent No.
US 12,350,349
App. No.
16/322,803
Granted
Jul 8, 2025
Kind
B2
Abstract

The present disclosure provides the use of fratricide-resistant chimeric antigen receptor T (CAR-T) cells targeting antigens expressed by T cell malignancies.

Claims (52)

1. A human primary T cell comprising a chimeric antigen receptor (CAR-T cell),

wherein the chimeric antigen receptor (CAR) specifically binds to CD7 and comprises a 4-1BB costimulatory domain, and

wherein the CAR-T cell comprises

a first genetic modification comprising a first indel in the genomic locus of CD7, wherein the first indel occurs at a position within:

80,274,181-80,274,203;

80,274,195-80,274,217;

80,274,238-80,274,260;

80,274,239-80,274,261;

80,274,555-80,274,577;

80,274,563-80,274,585;

80,274,569-80,274,591;

80,274,571-80,274,593;

80,274,580-80,274,602; or

80,274,586-80,274,608 of chromosome 17, wherein positional numbering is according to Genome Reference Consortium Human Build 37 (GRCh37); and

a second genetic modification comprising a second indel in the genomic locus of TRAC, wherein the second indel occurs at a position within 23,016,517-23,016,536 of chromosome 14, wherein positional numbering is according to Genome Reference Consortium Human Build 37 (GRCh37).

2. The human primary T cell of claim 1 , wherein the first indel occurs at a position within 80,274,181-80,274,203.

3. The human primary T cell of claim 1 , wherein the first indel occurs at a position within 80,274,195-80,274,217.

4. The human primary T cell of claim 1 , wherein the first indel occurs at a position within 80,274,238-80,274,260.

5. The human primary T cell of claim 1 , wherein the first indel occurs at a position within 80,274,239-80,274,261.

6. The human primary T cell of claim 1 , wherein the first indel occurs at a position within 80,274,555-80,274,577.

7. The human primary T cell of claim 1 , wherein the first indel occurs at a position within 80,274,563-80,274,585.

8. The human primary T cell of claim 1 , wherein the first indel occurs at a position within 80,274,569-80,274,591.

9. The human primary T cell of claim 1 , wherein the first indel occurs at a position within 80,274,571-80,274,593.

10. The human primary T cell of claim 1 , wherein the first indel occurs at a position within 80,274,580-80,274,602.

11. The human primary T cell of claim 1 , wherein the first indel occurs at a position within 80,274,586-80,274,608.

12. A human primary T cell comprising a chimeric antigen receptor (CAR-T cell),

wherein the chimeric antigen receptor (CAR) specifically binds to CD7, and

wherein the CAR-T cell comprises

a first genetic modification comprising a first indel in the genomic locus of CD7, wherein the first indel occurs within the genomic region targeted by any one of the sequences selected from SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO: 10, SEQ ID NO:11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO:15 or SEQ ID NO: 16; and

a second genetic modification comprising a second indel in the genomic locus of TRAC, wherein the second indel occurs within the genomic region targeted by residues 1-20 of SEQ ID NO: 19.

13. The human primary T cell of claim 12 , wherein the first indel occurs within the genomic region targeted by SEQ ID NO:7.

14. The human primary T cell of claim 12 , wherein the first indel occurs within the genomic region targeted by SEQ ID NO:8.

15. The human primary T cell of claim 12 , wherein the first indel occurs within the genomic region targeted by SEQ ID NO:9.

16. The human primary T cell of claim 12 , wherein the first indel occurs within the genomic region targeted by SEQ ID NO:10.

17. The human primary T cell of claim 12 , wherein the first indel occurs within the genomic region targeted by SEQ ID NO:11.

18. The human primary T cell of claim 12 , wherein the first indel occurs within the genomic region targeted by SEQ ID NO: 12.

19. The human primary T cell of claim 12 , wherein the first indel occurs within the genomic region targeted by SEQ ID NO:13.

20. The human primary T cell of claim 12 , wherein the first indel occurs within the genomic region targeted by SEQ ID NO:14.

21. The human primary T cell of claim 12 , wherein the first indel occurs within the genomic region targeted by SEQ ID NO:15.

22. The human primary T cell of claim 12 , wherein the first indel occurs within the genomic region targeted by SEQ ID NO:16.

23. The CAR-T cell of claim 1 or 12 , wherein the indel in the genomic locus of CD7 occurs within the genomic region targeted by residues 1-20 of SEQ ID NO:17 or SEQ ID NO:18.

24. The CAR-T cell of claim 1 or 12 , wherein the CAR comprises a signaling domain comprising a CD32 effector domain.

25. A population of two or more CAR-T cells of claim 1 or 12 , wherein the population is without contamination with malignant T cells.

26. The population of CAR-T cells of claim 25 , wherein the population comprises human primary T cells obtained from a donor who does not have a T cell malignancy.

27. A pharmaceutical composition comprising a therapeutically effective amount of the population of CAR-T cells of claim 25 .

28. The CAR-T cell of claim 1 or 12 , wherein CD7 and TRAC are genetically modified by multiplex gene editing.

29. A genetically modified human T cell, comprising a chimeric antigen receptor (CAR), the genetically modified T cell further comprising a genome comprising:

(a) a CD7 gene on chromosome 17 comprising an indel within a genomic sequence that is complementary to residues 1-20 of the sequence set forth in SEQ ID NO: 17 or SEQ ID NO: 18; and

(b) a TRAC gene on chromosome 14 comprising an indel within a genomic sequence that is complementary to residues 1-20 of the sequences set forth in SEQ ID NO:19,

wherein the CAR comprises a 4-1BB costimulatory domain and an antigen binding domain that specifically binds a CD7 antigen.

30. A pharmaceutical composition comprising a therapeutically effective amount of a population of CAR-T cells of claim 29 .

31. A complex comprising a guide RNA comprising any one of the sequences selected from SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO:16, SEQ ID NO: 17, or SEQ ID NO: 18, and a Cas9 protein.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 13, 2019
From: DIPERSIO, JOHN F.; COOPER, MATTHEW
To: WASHINGTON UNIVERSITY
Reel/Frame 051273/0046 →
Continuity (4)
Provisional Application 62505614 · May 12, 2017
Provisional Application 62482570 · Apr 6, 2017
Provisional Application 62370485 · Aug 3, 2016
Related Publication 20200000937A1 · Jan 2, 2020
References Cited (203)
US 5795572A · Diegel et al. · 1998 [cited by applicant]
US 7446190B2 · Sadelain et al. · 2008 [cited by applicant]
US 10201606B2 · Lutteropp et al. · 2019 [cited by applicant]
US 11390658B2 · Bari · 2022 [cited by examiner]
US 20030161809A1 · Houston et al. · 2003 [cited by applicant]
US 20120321667A1 · Sentman · 2012 [cited by applicant]
US 20130280220A1 · Ahmed et al. · 2013 [cited by applicant]
US 20150299317A1 · Orentas et al. · 2015 [cited by applicant]
US 20150342993A1 · Kloss et al. · 2015 [cited by applicant]
US 20160009813A1 · Themeli et al. · 2016 [cited by applicant]
US 20160144026A1 · Lutteropp et al. · 2016 [cited by applicant]
US 20160319367A1 · Bernards · 2016 [cited by examiner]
US 20170029777A1 · Pillai · 2017 [cited by applicant]
US 20170175128A1 · Welstead · 2017 [cited by examiner]
US 20170290858A1 · Zhao et al. · 2017 [cited by applicant]
US 20180008638A1 · Campana · 2018 [cited by examiner]
US 20180066034A1 · Ma · 2018 [cited by examiner]
US 20180104308A1 · Mamonkin et al. · 2018 [cited by applicant]
US 20180119123A1 · Gori · 2018 [cited by examiner]
US 20180148506A1 · Png et al. · 2018 [cited by applicant]
US 20180311269A1 · Lobb et al. · 2018 [cited by applicant]
US 20200000937A1 · DiPersio et al. · 2020 [cited by applicant]
US 20200040056A1 · DiPersio et al. · 2020 [cited by applicant]
US 20200071397A1 · DiPersio et al. · 2020 [cited by applicant]
IL 254141B · 2022 [cited by applicant]
JP 2015513394A · 2015 [cited by applicant]
JP 2017535261A · 2017 [cited by applicant]
WO 2003051926 · 2003 [cited by applicant]
WO 2003051926A2 · 2003 [cited by applicant]
WO 2011059836A2 · 2011 [cited by applicant]
WO 2013074916A1 · 2013 [cited by applicant]
WO 2013123061A1 · 2013 [cited by applicant]
WO 2013126729A1 · 2013 [cited by applicant]
WO 2013153391A1 · 2013 [cited by applicant]
WO 2013176915A1 · 2013 [cited by applicant]
WO 2014055668A1 · 2014 [cited by applicant]
WO 2014165707A2 · 2014 [cited by applicant]
WO 2014191128A1 · 2014 [cited by applicant]
WO 2015075175A1 · 2015 [cited by applicant]
WO 2015090229A1 · 2015 [cited by applicant]
WO 2015121454 · 2015 [cited by applicant]
WO 2015121454A1 · 2015 [cited by applicant]
WO 2015162211A1 · 2015 [cited by applicant]
WO 2016011210A2 · 2016 [cited by applicant]
WO 2016069282A1 · 2016 [cited by applicant]
WO 2016069283A1 · 2016 [cited by applicant]
WO 2016081518A2 · 2016 [cited by applicant]
WO 2016100236A2 · 2016 [cited by applicant]
WO 2016126608A1 · 2016 [cited by applicant]
WO 2016127257A1 · 2016 [cited by applicant]
WO 2016138491A1 · 2016 [cited by applicant]
WO 2016210293A1 · 2016 [cited by applicant]
WO 2017023803A1 · 2017 [cited by applicant]
WO 2017062451A1 · 2017 [cited by applicant]
WO 2017070429 · 2017 [cited by applicant]
WO 2017088012A1 · 2017 [cited by applicant]
WO 2017112877A1 · 2017 [cited by applicant]
WO 2017127729A1 · 2017 [cited by applicant]
WO 2017147538A1 · 2017 [cited by applicant]
WO 2017149515A1 · 2017 [cited by applicant]
WO 2017193059A1 · 2017 [cited by applicant]
WO 2017197347A1 · 2017 [cited by applicant]
WO 2017213979A1 · 2017 [cited by applicant]
WO 2017222593A1 · 2017 [cited by applicant]
WO 2018007263A1 · 2018 [cited by applicant]
WO 2018026953A1 · 2018 [cited by applicant]
WO 2018027036A1 · 2018 [cited by applicant]
WO 2018098306A1 · 2018 [cited by applicant]
WO 2018195339A1 · 2018 [cited by applicant]
WO 2019232409A1 · 2019 [cited by applicant]
WO 2019232425A1 · 2019 [cited by applicant]
WO 2019232444A1 · 2019 [cited by applicant]
WO 2019232477A2 · 2019 [cited by applicant]
WO 2020232427A2 · 2020 [cited by applicant]
Vandermeulen et al. New Generation of Plasmid Backbones Devoid of Antibiotic Resistance Marker for Gene Therapy Trials. (Mol Ther, 2011, 19:1942-1949) (Year: 2011). [cited by examiner]
Lee et al. Immunologic Characterization of CD7-Deficient Mice1, (Journal of Immunology, 1998, 160:5749-5736). (Year: 1998). [cited by examiner]
“Use of Immunophenotyping/Genetic Testing in Differential Diagnosis of Mature B-Cell and NK/T-Cell Neoplasms,” NCCN Clinical Practice Guidelines in Oncology, Non-Hodgkin's Lymphomas, Mar. 3, 2015, 11 pgs., Version 2.201… [cited by applicant]
Cooper, M. et al., “An ‘off-the-shelf’ fratricide-resistant CAR-T for the treatment of T cell hematologic malignancies,” HHS Public Access Author Manuscript, Aug. 20, 2018, pp. 1-23, published in final edited form as: L… [cited by applicant]
Heczey, A. et al., “Invariant NKT cells with chimeric antigen receptor provide a novel platform for safe and effective cancer immunotherapy,” Blood, 2014, pp. 2824-2833, vol. 124, No. 18. [cited by applicant]
International Search Report and Written Opinion dated Dec. 19, 2019 from related Patent Application No. PCT/ US2019/035052; 14 pgs. [cited by applicant]
Extended European Search Report dated Feb. 18, 2020 from related European Patent Application No. 17837687.7; 6 pgs. [cited by applicant]
Savoldo, B. et al., “Epstein Barr virus-specific cytotoxic T lymphocytes expressing the anti-CD30zeta artificial chimeric T-cell receptor for immunotherapy of Hodgkin disease,” Blood, Oct. 1, 2007, pp. 2620-2630, vol. 1… [cited by applicant]
Fehse, B. et al., “CD34 Splice Variant: an Attractive Marker for Selection of Gene-Modified Cells,” Mol. Ther., 2000, pp. 448-456, vol. 1, No. 5. [cited by applicant]
Norell, H. et al., “CD34-Based Enrichment of Genetically-Engineered Human T Cells for Clinical Use Results in Dramatically Enhanced Tumor Targeting,” NIH Public Access Author Manuscript, Aug. 7, 2013, pp. 1-22, publishe… [cited by applicant]
Office Action dated Jul. 6, 2021 from related U.S. Appl. No. 16/428,624; 14 pgs. [cited by applicant]
Kleinstiver, B. et al., “High-fidelity CRISPR-Cas9 nucleases with no detectable genome-wide off-target effects,” Nat., Jan. 28, 2016, pp. 490-495, vol. 529. [cited by applicant]
International Search Report and Written Opinion dated Nov. 12, 2019 from related Patent Application No. PCT/US2019/035010; 14 pgs. [cited by applicant]
NCBI Reference Sequence NP_001139345.1; Sep. 16, 2019; 4 pgs. [cited by applicant]
Zheng, W. et al., “Modulation of PI3K signaling to improve CAR T cell function,” Oncotarget, 2018, pp. 35807-35808, vol. 9, No. 88. [cited by applicant]
Office Action dated May 11, 2021 from related European Patent Application No. 17837687.7; 5 pgs. [cited by applicant]
Bonilla, F. et al., “Targeted gene disruption of murine CD7,” International Immunol., 1997, pp. 1875-1883, vol. 9, No. 12. [cited by applicant]
Bonini, C. et al., “Adoptive T-cell therapy for cancer: the era of engineered T-cells,” Eur. J. Immunol., 2015, pp. 2457-2469, vol. 45, Wiley-VCH Verlag Gmbh & Co. KGaA, Weinheim. [cited by applicant]
Campana, D. et al., “Immunophenotyping of leukemia,” J. Immunol. Methods, Sep. 21, 2000, pp. 59-75, vol. 243, Nos. 1-2. [cited by applicant]
Cooke, K. et al., “An Experimental Model of Idiopathic Pneumonia Syndrome After Bone Marrow Transplantation: I. The Roles of Minor H Antigens and Endotoxin,” Blood, Oct. 15, 1996, pp. 3230-3239, vol. 8, No. 8. [cited by applicant]
Eissenberg, L. et al., “Suicide genes: monitoring cells in patients with a safety switch,” Frontiers Pharmacol., Nov. 2014, pp. 1-4, vol. 5, No. 241. [cited by applicant]
Eissenberg, L. et al., “[18F]FHBG PET/CT Imaging of CD34-TK75 Transduced Donor T Cells in Relapsed Allogeneic Stem Cell Transplant Patients: Safety and Feasibility,” Mol. Ther., Jun. 2015, pp. 1110-1122, vol. 23, No. 6. [cited by applicant]
Eyquem, J. et al., “Targeting a CAR to the TRAC locus with CRISPR/Cas9 enhances tumour rejection,” HHS Public Access Author Manuscript, Sept. 2, 2017, pp. 1-28, published in final edited form as: Nat., Mar. 2, 2017, pp.… [cited by applicant]
Galetto, R. et al., “Pre-TCRalpha supports CD3-dependent reactivation and expansion of TCRalpha-deficient primary human T-cells,” Mol. Ther. Methods Clin. Dev., 2014, pp. 1-9, vol. 14021. [cited by applicant]
Gerby, B. et al., “Expression of CD34 and CD7 on human T-cell acute lymphoblastic leukemia discriminates functionally heterogeneous cell populations,” Leukemia, 2011, pp. 1249-1258, vol. 25. Macmillan Publishers Limited. [cited by applicant]
Gokbuget, N. et al., “Treatment of Adult ALL According to Protocols of the German Multicenter Study Group for Adult ALL (GMALL),” Acute Leukemias, 2008, pp. 167-176, Chapter 13. [cited by applicant]
Gokbuget, N. et al., “High single-drug activity of nelarabine in relapsed T-lymphoblastic leukemia/lymphoma offers curative option with subsequent stem cell transplantation,” Blood, Sep. 29, 2011, pp. 3504-3511, vol. 11… [cited by applicant]
Goldberg, J. et al., “Childhood T-Cell Acute Lymphoblastic Leukemia: the Dana-Farber Cancer Institute Acute Lymphoblastic Leukemia Consortium Experience,” J. Clin. Oncol., Oct. 1, 2003, pp. 3616-3622, vol. 21, No. 19. [cited by applicant]
Gomes-Silva, D. et al., “CD7-edited T cells expressing a CD7-specific CAR for the therapy of T-cell malignancies,” Blood, Jul. 20, 2017, pp. 285-296, vol. 130, No. 3. [cited by applicant]
Hendel, A. et al., “Chemically modified guide RNAs enhance CRISPR-Cas genome editing in human primary cells,” Nat. Biotechnol., 2015, pp. 985-989, vol. 33. [cited by applicant]
International Search Report and Written Opinion dated Oct. 18, 2017 from related Patent Application No. PCT/US2017/045304; 12 pgs. [cited by applicant]
Karrman, K. et al., “Pediatric T-cell acute lymphoblastic leukemia,” Genes, Chromosomes and Cancer, Feb. 2017, pp. 89-116, vol. 56, No. 2. [cited by applicant]
Khalidi, H. et al., “Acute Lymphoblastic Leukemia: Survey of Immunophenotype, French-American-British Classification, Frequency of Myeloid Antigen Expression, and Karyotypic Abnormalities in 210 Pediatric and Adult Case… [cited by applicant]
Kochenderfer, J. et al., “Chemotherapy-Refractory Diffuse Large B-Cell Lymphoma and Indolent B-Cell Malignancies Can Be Effectively Treated With Autologous T Cells Expressing an Anti-CD19 Chimeric Antigen Receptor,” J. … [cited by applicant]
Lee, D. et al., “The Future Is Now: Chimeric Antigen Receptors as Net Targeted Therapies for Childhood Cancer,” Clin. Cancer Res., May 15, 2012, pp. 2780-2790, vol. 18, No. 10. [cited by applicant]
Litzow, M. et al., “How I treat T-cell acute lymphoblastic leukemia in adults,” Blood, Aug. 13, 2015, pp. 833-841, vol. 126, No. 7. [cited by applicant]
Ma, H. et al., “T-cell lymphomas, a challenging disease: types, treatments, and future,” Int. J. Clin. Oncol., Feb. 2017, pp. 18-51, vol. 22, No. 1. [cited by applicant]
MacLeod, D. et al., “Integration of a CD19 CAR into the TCR Alpha Chain Locus Streamlines Production of Allogeneic Gene-Edited CAR T Cells,” Mol. Ther., Apr. 2017, pp. 949-961, vol. 25, No. 4. [cited by applicant]
Mamonkin, M. et al., “A T-cell-directed chimeric antigen receptor for the selective treatment of T-cell malignancies,” Blood, Aug. 20, 2015, pp. 983-992, vol. 126, No. 8. [cited by applicant]
Marks, D. et al., “T-cell acute lymphoblastic leukemia in adults: clinical features, immunophenotype, cytogenetics, and outcome from the large randomized prospective trial (UKALL XII/ECOG 2993),” Blood, Dec. 10, 2009, p… [cited by applicant]
Milush, J. et al., “Functionally distinct subsets of human NK cells and monocyte/DC-like cells identified by coexpression of CD56, CD7, and CD4,” Blood, Nov. 26, 2009, pp. 4823-4831, vol. 114, No. 23. [cited by applicant]
Miwa, H. et al., “Biological Characteristics of CD7(+) Acute Leukemia,” Leuk. Lymphoma, Apr. 1996, pp. 239-244, vol. 21, Harwood Academic Publishers GmbH, The Netherlands. [cited by applicant]
Osborn, M. et al., “Evaluation of TCR Gene Editing Achieved by TALENs, CRISPR/Cas9, and megaTAL Nucleases,” Mol. Ther., Mar. 2016, pp. 570-581, vol. 24, No. 3. [cited by applicant]
Park, J. et al., “CD19-targeted CAR T-cell therapeutics for hematologic malignancies: interpreting clinical outcomes to date,” Blood, Jun. 30, 2016, pp. 3312-3320, vol. 127, No. 26. [cited by applicant]
Patel, J. et al.. “The immunophenotype of T-lymphoblastic lymphoma in children and adolescents: a Children's Oncology Group report,” British J. Haematol., 2012, pp. 454-461, vol. 159, Blackwell Publishing Ltd. [cited by applicant]
Pinz, K. et al., “Preclinical targeting of human T-cell malignancies using CD4-specific chimeric antigen receptor (CAR)-engineered T cells,” Leukemia, 2016, pp. 701-707, vol. 30. [cited by applicant]
Porter, D. et al., “Chimeric antigen receptor T cells persist and induce sustained remissions in relapsed refractory chronic lymphocytic leukemia,” Sci. Transl. Med., Sept. 2, 2015, pp. 1-12, vol. 7, No. 303, 303ra139. [cited by applicant]
Qasim, W. et al., “Molecular remission of infant B-ALL after infusion of universal TALEN gene-edited CAR T cells,” Sci. Transl. Med., Jan. 25, 2017, pp. 1-8, vol. 9, No. 374. [cited by applicant]
Reinhold, U. et al., “CD7-negative T cells represent a separate differentiation pathway in a subset of post-thymic helper T cells,” Immunology, 1996, pp. 391-396, vol. 89. [cited by applicant]
Stock, W. et al., “Alemtuzumab can be Incorporated Into Front-Line Therapy of Adult Acute Lymphoblastic Leukemia (ALL): Final Phase I Results of a Cancer and Leukemia Group B Study (CALGB 10102),” Blood, 51st ASH Annual… [cited by applicant]
Tiftik, N. et al., “The importance of CD7 and CD56 antigens in acute leukaemias,” Int. J. Clin. Practice, Feb. 2004, pp. 149-152, vol. 58, No. 2. [cited by applicant]
Tsai, S. et al., “GUIDE-Seq enables genome-wide profiling of off-target cleavage by CRISPR-Cas nucleases,” HHS Public Access Author Manuscript, Aug. 1, 2015, pp. 1-23, published in final edited form as: Nat. Biotech., F… [cited by applicant]
Kirberg, Peripheral T Cell Survival Required Continual Ligation of the T Cell Receptor to Major Histocompatibility Complex-Encoded Molecules, J. Exp. Med., Oct. 20, 1997, vol. 186, No. 8, pp. 12699-1275. [cited by applicant]
Rappl, The CD7-subset of CD4+ memory T cells is prone to accelerated apoptosis that is prevented by Interleukin-15 (IL-15), Cell Death and Differentiation, 2001, vol. 8, pp. 395-402. [cited by applicant]
Deyev, S. et al., “Multivalency: the hallmark of antibodies used for optimization of tumor targeting by design,” BioEssays, 2008, pp. 904-918, vol. 30, Wiley Periodicals, Inc. [cited by applicant]
Harrer, D. et al., “Chimeric Antigen Receptors in Different Cell Types: New Vehicles Join the Race,” Human Gene Ther., Jan. 2018, pp. 547-558, vol. 29, No. 5. [cited by applicant]
Mack, M. et al., “A small bispecific antibody construct expressed as a functional single-chain molecule with high tumor cell cytotoxicity,” PNAS, Jul. 1995, pp. 7021-7025, vol. 92. [cited by applicant]
Office Action dated Apr. 15, 2022 from related U.S. Appl. No. 16/428,789; 28 pgs. [cited by applicant]
Carpenito, C. et al., “Control of large, established tumor xenografts with genetically retargeted human T cells containing CD28 and CD137 domains,” PNAS, Mar. 3, 2009, pp. 3360-3365, vol. 106, No. 9. [cited by applicant]
Extended European Search Report dated Apr. 8, 2022 from related European Patent Application No. 19811980.2; 10 pgs. [cited by applicant]
Karpanen, T. et al., “T-cell receptor gene therapy—ready to go viral?,” Mol. Oncol., Oct. 2015, pp. 2019-2042, vol. 9. [cited by applicant]
Office Action dated Mar. 8, 2022 from related Japanese Patent Application No. 2019-527775; 7 pgs., with English translation. [cited by applicant]
Orentas, R. et al., “Bioinformatic description of immunotherapy targets for pediatric T-cell leukemia and the impact of normal gene sets used for comparison,” Front. Oncol., Jun. 2014, pp. 1-11, vol. 4, No. 134. [cited by applicant]
Written Opinion and Search Report dated Mar. 15, 2022 from related Singaporean Patent Application No. 11201900772Y; 11 pgs. [cited by applicant]
Extended European Search Report dated Feb. 16, 2022 from related European Patent Application No. 19810294.9; 9 pgs. [cited by applicant]
Office Action dated Feb. 22, 2022 from related U.S. Appl. No. 16/428,624; 16 pgs. [cited by applicant]
Rotolo, A., “CAR-iNKT cells as a novel immunotherapy for B cells malignancies,” Author Thesis, Imperial College London, Apr. 2018, 209 pgs.; https://doi.org/10.25560/82147. [cited by applicant]
Office Action dated May 25, 2021 from related Japanese Patent Application No. 2019-527775; 10 pgs., with English translation. [cited by applicant]
The Journal of the Japanese Society of Internal Medicine, 2008, pp. 1553-1560, vol. 97, No. 7. [cited by applicant]
Chinese Application No. 201780061572.2; First Office Action issued Jun. 22, 2022, 6 pgs. [cited by applicant]
Chinese Application No. 201780061572.2; Second Office Action issued Jan. 12, 2023, 4 pgs. [cited by applicant]
South Korean Application No. 10-2019-7006314, Office Action issued Sep. 29, 2022, 5 pgs. [cited by applicant]
Gerby, et al., Expression of CD34 and CD7 on human T-cell acute lymphoblastic leukemia discriminates functionally heterogeneous cell populations; Leukemia, 2011, vol. 25, Nature, pp. 1249-1258. [cited by applicant]
Mamonkin, et al., A T-cell-directed chimeric antigen receptor for the selective traetment of T-cell malignancies; Blood, Aug. 20, 2015, vol. 126, No. 8, pp. 983-992. [cited by applicant]
Rettig, Transduction and Selection of Human T Cells with Novel CD34/Thymidine Kinase Chimeric Suicide Genes for the Treatment of Graft versus-Host Disease; Molecular Therapy., Jul. 2003, vol. 8, No. 1, pp. 29-41. [cited by applicant]
Austrialian Application No. 2017306557; Examination Report issued Jul. 19, 2022, 4 pages. [cited by applicant]
Doronin I.I., et al., “Ganglioside GD2 in Reception and Transduction of Cell Death Signal in Tumor Cells,” BMC Cancer 2014, vol. 14, No. 295, 17 pages. [cited by applicant]
International Preliminary Report on Patentability for International Application No. PCT/US2017/045304, mailed Feb. 14, 2019, 9 pages. [cited by applicant]
International Preliminary Report on Patentability for International Application No. PCT/US2019/035010, mailed Dec. 10, 2020, 10 Pages. [cited by applicant]
International Preliminary Report on Patentability for International Application No. PCT/US2019/035052, mailed Dec. 10, 2020, 10 Pages. [cited by applicant]
Marrero I., et al., “Type II NKT Cells in Inflammation, Autoimmunity, Microbial Immunity, and Cancer,” Frontiers in Immunology, Jun. 17, 2015, vol. 6, No. 316, 6 Pages. [cited by applicant]
Oh S.J., et al., “Role of Type II NKT Cells in the Suppression of Graft-Versus-Host Disease,” Critical Reviews in Immunology, 2008, vol. 28, No. 3, pp. 249-267. [cited by applicant]
Ren J., et al., “Multiplex Genome Editing to Generate Universal CAR T Cells Resistant to PD1 Inhibition,” Clinical Cancer Research, May 1, 2017, vol. 23, No. 9, pp. 2255-2266, doi:10.1158/1078-0432.CCR-16-1300. [cited by applicant]
Shearer R.F., et al., “Experimental Design for Stable Genetic Manipulation in Mammalian Cell Lines: Lentivirus and Alternatives,” Genes to Cells, 2015, vol. 20, pp. 1-10. [cited by applicant]
Singh A.K., et al., “Type II NKT Cells: an Elusive Population With Immunoregulatory Properties,” Frontiers in Immunology, Aug. 28, 2018, vol. 9, Article 1969, 8 Pages. [cited by applicant]
Ku X., et al., “The basics of CAR T Design and Challenges in Immunotherapy of Solid Tumors—Ovarian Cancer as a Model,” Human Vaccines Immunotherapeutics, 2017, vol. 13, No. 7, 1548-1555, doi: 10.1080/21645515.2017.12914… [cited by applicant]
ATCC Catalog, CCRF-CEM (CCL-119™), available at www.atcc.org/products/ccl-119. [cited by applicant]
ATCC Catalog, MOLT-4 (CRL-1582™), available at www.atcc.org/products/crl-1582. [cited by applicant]
ATCC Catalog, NK-92® (CRL-2407™), available at www.atcc.org/products/crl-2407. [cited by applicant]
Fabian, et al., “The emerging role of off-the-shelf engineered natural killer cells in targeted cancer immunotherapy,” Mal Ther Oncol, vol. 23, pp. 266-276 (2021). [cited by applicant]
You, et al., “A novel CD7 chimeric antigen receptor-modified NK-92MI cell line targeting T-cell acute lymphoblastic leukemia,” Am J Cancer Res, vol. 9(1), pp. 64-78 (Jan. 1, 2019). [cited by applicant]
Data Robustness and Reproducibility in Gene Editing Applications: Today's Limits and Tomorrow's Potential, GEN: Gen Eng and Biotech News 40(S4):S9-S13 (2020). [cited by applicant]
Examination Report No. 2 for Australian Application No. 2017306557, mailed on Jun. 27, 2023, 3 pages. [cited by applicant]
Office Action for Canadian Patent Application No. 3032429, mailed on Jul. 5, 2023, 6 pages. [cited by applicant]
Office Action for Russian Patent Application No. 2020143576, dated Dec. 7, 2022, 14 pages. [cited by applicant]
Costa, et al., Genome Editing Using Engineered Nucleases and Their Use in Genomic Screening, the Assay Guidance Manual, Nov. 20, 2017, pp. 1-24. [cited by applicant]
Faure, et al., Comparative genomics and evolution of trans-activating RNAs in Class 2 CRISPR-Cas systems, RNA Biology, 2019, vol. 16, No. 4, pp. 435-448. [cited by applicant]
Jinek, et al., A Programmable Dual-RNA-Guided DNA Endonuclease in Adaptive Bacterial immunity, Science, 2012, vol. 333, pp. 816-821. [cited by applicant]
Ran, et al., Genome engineering using the CRISPR-Cas9 system, Nature Protocols, 2013, vol. 8, No. 11, pp. 2281-2308. [cited by applicant]
Scott, et al., Targeted genome regulation and modification using transcription activator-like effectors, FEBS Journal, 2014, vol. 281, pp. 4583-4597. [cited by applicant]
Schanberg, et al., Isolation and characterization of the demonic human CD7 gene: structural similarity with the murine Thy-1 gene, PNAS, 1991, vol. 88.2, pp. 603-607. [cited by applicant]
Varshney, et al., A high-throughput functional genomics workflow based on CRISPR/Cas9-mediated targeted mutagenesis in zebrafish, Nature Protocols, 2016, vol. 11(12), pp. 2357-2375. [cited by applicant]
Ghobadi, et al., Anti-CD7 allogeneic WU-CART-007 in patients with replased/refractory T-cell acute lymphoblastic leukemia/lymphoma: a phase ½ trial, Research Square, 2024, 1 pg. [cited by applicant]
Thorsen, et al., Tumor-specific usage of alternative transcription start sites in colorectal cancer identified by genome-wide exon array analysis, BMC Genomics, 2011, vol. 12, pp. 1-14. [cited by applicant]
Badri H., et al., “Optimization of Radiation Dosing Schedules for Proneural Glioblastoma,” Journal of Mathematical Biology, Jun. 21, 2015, vol. 72, 36 pages. [cited by applicant]
Baylot V., et al., “TCTP Has a Crucial Role in the Different Stages of Prostate Cancer Malignant Progression,” TCTP/tpt1-Remodeling Signaling from Stem Cell to Disease, 2017, vol. 64, pp. 255-261. [cited by applicant]
Dai Q., et al., “4-1BB Signaling Boosts the Anti-Tumor Activity of CD28-Incorporated 2nd Generation Chimeric Antigen Receptor-Modified T Cells,” Frontiers in Immunology, Nov. 13, 2020, vol. 11, Article No. 539654, pp. 1… [cited by applicant]
Decision on Rejection for Chinese Patent Application No. 201780061572.2, mailed on Nov. 21, 2023, 10 pages. [cited by applicant]
Final Office Action for U.S. Appl. No. 16/428,624 mailed on Feb. 2, 2022, 24 Pages. [cited by applicant]
Final Office Action for U.S. Appl. No. 16/428,624 mailed on May 30, 2023, 25 Pages. [cited by applicant]
First Office Action and Search Report for Chinese Patent Application No. 201980050879.1, dated Oct. 10, 2022, 16 pages. [cited by applicant]
Jahn E.M., et al., “How to Systematically Evaluate Immunogenicity of Therapeutic Proteins—Regulatory Considerations,” New Biotechnology, Jun. 2009, vol. 25, No. 5, pp. 280-286. [cited by applicant]
Jinek M., et al., “A Programmable Dual-RNA-Guided DNA Endonuclease in Adaptive Bacterial Immunity,” Science, Aug. 17, 2012, vol. 337, pp. 816-821. [cited by applicant]
Kontermann R.E., et al., “Bispecific Antibodies,” Drug Discovery Today, Jul. 2015, vol. 20, No. 7, pp. 838-847. [cited by applicant]
Kulemzin S.V., et al., “Fundamentals of the Design of Chimeric Antigenic Receptors,” Acta Naturae (Russian version), 2017, vol. 9, No. 1, pp. 6-15. [cited by applicant]
Non Final Office Action for U.S. Appl. No. 16/428,624 mailed on Sep. 13, 2022, 31 Pages. [cited by applicant]
Office Action and Search Report for Russian Patent Application No. 2020143576, dated May 4, 2023, 21 pages. [cited by applicant]
Office Action for Japanese Patent Application No. 2020-566909, mailed on Jun. 13, 2023, 10 Pages. [cited by applicant]
Office Action for Japanese Patent Application No. 2020-566909, mailed on Nov. 28, 2023, 4 Pages. [cited by applicant]
Ran F.A., et al., “Genome Engineering Using the CRISPR-Cas9 System,” Nature Protocols, Oct. 24, 2013, vol. 08, No. 11, pp. 2281-2308. [cited by applicant]
Rappl G., et al., “The CD3-Zeta Chimeric Antigen Receptor Overcomes TCR Hypo-Responsiveness of Human Terminal Late-Stage T Cells,” PLoS One, Jan. 2012, vol. 7, No. 1, pp. 1-10. [cited by applicant]
Sadelain, et al., The Basic Principles of Chimeric Antigen Receptor Design, Cancer Discovery, Apr. 2013, vol. 3, Issue 4, pp. 388-398. [cited by applicant]
Scott N.F.J., et al., “Targeted Genome Regulation and Modification Using Transcription Activator-like Effectors,” FEBS Journal, 2014, vol. 281, No. 20, pp. 4583-4597, doi:10.1111/febs.12973. [cited by applicant]
Second Office Action for Chinese Patent Application No. 201980050879.1, dated Sep. 16, 2023, 12 pages. [cited by applicant]
Tang X.Y., et al., “Third-Generation CD28/4-1BB Chimeric Antigen Receptor T Cells for Chemotherapy Relapsed or Refractory Acute Lymphoblastic Leukaemia: a Non-Randomised, Open-Label Phase I Trial Protocol,” BMJ Open, 20… [cited by applicant]
Textor A., et al., “CD28 Co-Stimulus Achieves Superior CAR T Cell Effector Function against Solid Tumors Than 4-1BB Co-Stimulus,” Cancers, Mar. 2, 2021, vol. 13, No. 5, pp. 1-17. [cited by applicant]
Third Office Action for Chinese Patent Application No. 201780061572.2, mailed on Jul. 18, 2023, 12 pages. [cited by applicant]
Weinkove R., et al., “Selecting Costimulatory Domains for Chimeric Antigen Receptors: Functional and Clinical Considerations,” Clinical Translational Immunology, May 11, 2019, vol. 8, No. 5, 14 pages. [cited by applicant]
Zhao X., et al., “Efficacy and Safety of CD28- or 4-1BB-Based CD19 CAR-T Cells in B Cell Acute Lymphoblastic Leukemia,” Molecular Therapy: Oncolytics, 2020, vol. 18, 18 pages. [cited by applicant]