IP Library › Granted Patent US 12,193,995
Granted Patent B2
US 12,193,995 · App. 16/864,418 · Granted Jan 14, 2025

Method to treat cancer with engineered T-cells

Inventors: Boro Dropulic (Ellicott City, MD); Rimas J. Orentas (Seattle, WA); Dina Schneider (Potomac, MD); Winfried Krueger (Kensington, MD)
Assignee: LENTIGEN TECHNOLOGY, INC.
C12N5/0636A61K38/177A61K38/1774A61K39/4611A61K39/4631A61K39/4632A61K39/464499C07K14/7051C07K2319/03C12N2502/1121C12N2510/00C12N2740/16043
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Quick Facts
Patent No.
US 12,193,995
App. No.
16/864,418
Granted
Jan 14, 2025
Kind
B2
Abstract

Novel adoptive immunotherapy compositions comprising co-cultured lentiviral vector-transduced autologous antigen presentation cells and T cells are provided herein as well as are methods of use of same in a patient-specific combination immunotherapy that can be used to treat cancers and other diseases and conditions.

Claims (12)

1. An adoptive immunotherapy composition comprising an autologous T-cell population transduced with one or more lentiviral vectors encoding single or multiple chimeric antigen receptors (CARs), the single or multiple CARs comprising an isolated nucleic acid sequence selected from the group consisting of the nucleic acid sequences of SEQ ID NO: 13, SEQ ID NO: 17, and SEQ ID NO: 19, wherein the T cells are co-cultured with autologous antigen presentation cells transduced with one or more lentiviral vectors expressing patient-derived tumor antigens thereby generating an active patient-specific autologous anti-tumor T-cell population capable of promoting in vivo expansion and persistence of patient-specific anti-tumor T-cells resulting in tumor stabilization, tumor reduction, remission of cancer, or elimination of cancer in a patient-specific manner.

2. The adoptive immunotherapy composition of claim 1 , wherein the T-cell population is additionally transduced with one or more lentiviral vectors encoding tumor-specific T-cell receptors (TCRs).

3. The adoptive immunotherapy composition of claim 1 , wherein the T cells are T cells of a human having a cancer.

4. The adoptive immunotherapy composition of claim 1 , wherein the cancer is a hematological cancer, and wherein the hematological cancer is leukemia, lymphoma, or multiple myeloma.

5. The adoptive immunotherapy composition of claim 4 , wherein the leukemia is chronic lymphocytic leukemia (CLL), acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), or chronic myelogenous leukemia (CML).

6. The adoptive immunotherapy composition of claim 4 , wherein the lymphoma is mantle cell lymphoma, non-Hodgkin's lymphoma or Hodgkin's lymphoma.

7. The adoptive immunotherapy composition of claim 3 , wherein the cancer is an oral and pharynx cancer, a digestive system cancer, a respiratory system cancer, a bone and joint cancer, a soft tissue cancer, a skin cancer, a pediatric cancer, a cancer of the central nervous system, a cancer of the breast, a cancer of the genital system, a cancer of the urinary system, a cancer of the eye and orbit, a cancer of the endocrine system, and a cancer of the brain, or a combination thereof.

8. The adoptive immunotherapy composition of claim 1 , wherein the autologous antigen presentation cells are autologous dendritic cells differentiated from monocytes.

9. The adoptive immunotherapy composition of claim 1 , wherein the T cell has been preselected by virtue of expressing specific activation or memory-associated surface markers.

10. The adoptive immunotherapy composition of claim 1 , wherein the T cells and the autologous presentation cells are isolated from a hematopoietic stem cell donor, and wherein the procedure is carried out in the context of hematopoietic stem cell transplantation.

11. The adoptive immunotherapy composition of claim 2 , wherein the T cell has been preselected by virtue of expressing specific activation or memory-associated surface markers.

12. The adoptive immunotherapy composition of claim 2 , wherein the T cells and the autologous presentation cells are isolated from a hematopoietic stem cell donor, and wherein the procedure is carried out in the context of hematopoietic stem cell transplantation.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 18, 2021
From: DROPULIC, BORO; ORENTAS, RIMAS J.; SCHNEIDER, DINA; KRUEGER, WINFRIED
To: LENTIGEN TECHNOLOGY, INC.
Reel/Frame 058153/0398 →
Continuity (3)
Division 15735921
Provisional Application 62175003 · Jun 12, 2015
Related Publication 20200297769A1 · Sep 24, 2020
References Cited (207)
US 3060165A · Craig · 1962 [cited by applicant]
US 3896111A · Kupchan · 1975 [cited by applicant]
US 4137230A · Hashimoto · 1979 [cited by applicant]
US 4151042A · Higashide · 1979 [cited by applicant]
US 4235871A · Papahadjopoulos · 1980 [cited by applicant]
US 4248870A · Miyashita · 1981 [cited by applicant]
US 4256746A · Miyashita · 1981 [cited by applicant]
US 4260608A · Miyashita · 1981 [cited by applicant]
US 4265814A · Hashimoto · 1981 [cited by applicant]
US 4294757A · Asai · 1981 [cited by applicant]
US 4307016A · Asai · 1981 [cited by applicant]
US 4308268A · Miyashita · 1981 [cited by applicant]
US 4308269A · Miyashita · 1981 [cited by applicant]
US 4309428A · Miyashita · 1982 [cited by applicant]
US 4313946A · Powell · 1982 [cited by applicant]
US 4315929A · Freedmna · 1982 [cited by applicant]
US 4317821A · Miyashita · 1982 [cited by applicant]
US 4322348A · Asai · 1982 [cited by applicant]
US 4331598A · Hasegawa · 1982 [cited by applicant]
US 4361650A · Asai · 1982 [cited by applicant]
US 4362663A · Kida · 1982 [cited by applicant]
US 4364866A · Asai · 1982 [cited by applicant]
US 4371533A · Akimoto · 1983 [cited by applicant]
US 4424219A · Hashimoto · 1984 [cited by applicant]
US 4450254A · Isley · 1984 [cited by applicant]
US 4486414A · Pettit · 1984 [cited by applicant]
US 4501728A · Geho · 1985 [cited by applicant]
US 4689401A · Ferris · 1987 [cited by applicant]
US 4816444A · Pettit · 1989 [cited by applicant]
US 4837028A · Allen · 1989 [cited by applicant]
US 4879278A · Pettit · 1989 [cited by applicant]
US 4880935A · Thorpe · 1989 [cited by applicant]
US 4902505A · Pardridge · 1990 [cited by applicant]
US 4957735A · Huang · 1990 [cited by applicant]
US 4978744A · Pettit · 1990 [cited by applicant]
US 4986988A · Pettit · 1991 [cited by applicant]
US 5004697A · Pardridge · 1991 [cited by applicant]
US 5019369A · Presant · 1991 [cited by applicant]
US 5055303A · Riley, Jr. · 1991 [cited by applicant]
US 5076973A · Pettit · 1991 [cited by applicant]
US 5079163A · Piatak, Jr · 1992 [cited by applicant]
US 5122368A · Greenfield · 1992 [cited by applicant]
US 5138036A · Pettit · 1992 [cited by applicant]
US 5188837A · Domb · 1993 [cited by applicant]
US 5208020A · Chari · 1993 [cited by applicant]
US 5208021A · Johnson · 1993 [cited by applicant]
US 5254342A · Shen · 1993 [cited by applicant]
US 5268164A · Kozarich · 1993 [cited by applicant]
US 5271961A · Mathiowitz · 1993 [cited by applicant]
US 5410024A · Pettit · 1995 [cited by applicant]
US 5413797A · Khan · 1995 [cited by applicant]
US 5416064A · Chari · 1995 [cited by applicant]
US 5449752A · Fujii · 1995 [cited by applicant]
US 5504191A · Pettit · 1996 [cited by applicant]
US 5506206A · Kozarich · 1996 [cited by applicant]
US 5514670A · Friedman · 1996 [cited by applicant]
US 5521284A · Pettit · 1996 [cited by applicant]
US 5530097A · Pettit · 1996 [cited by applicant]
US 5534496A · Lee · 1996 [cited by applicant]
US 5554725A · Pettit · 1996 [cited by applicant]
US 5599902A · Pettit · 1997 [cited by applicant]
US 5622929A · Willner · 1997 [cited by applicant]
US 5635483A · Pettit · 1997 [cited by applicant]
US 5663149A · Pettit · 1997 [cited by applicant]
US 5665860A · Pettit · 1997 [cited by applicant]
US 5780588A · Pettit · 1998 [cited by applicant]
US 5792458A · Johnson · 1998 [cited by applicant]
US 5824805A · King · 1998 [cited by applicant]
US 6034065A · Pettit · 2000 [cited by applicant]
US 6214345B1 · Firestone · 2001 [cited by applicant]
US 6239104B1 · Pettit · 2001 [cited by applicant]
US 6323315B1 · Pettit · 2001 [cited by applicant]
US 6441163B1 · Chari · 2002 [cited by applicant]
US 6884869B2 · Senter · 2005 [cited by applicant]
US 7338929B2 · Debinski · 2008 [cited by applicant]
US 7964567B2 · Doronina · 2011 [cited by applicant]
US 10421810B2 · Orentas · 2019 [cited by examiner]
US 10639329B2 · Dropulic et al. · 2020 [cited by applicant]
US 20020197266A1 · Debinski · 2002 [cited by applicant]
US 20030059854A1 · Means · 2003 [cited by applicant]
US 20040101519A1 · June et al. · 2004 [cited by applicant]
US 20050238649A1 · Doronina · 2005 [cited by applicant]
US 20060024317A1 · Boyd · 2006 [cited by applicant]
US 20060074008A1 · Senter · 2006 [cited by applicant]
US 20110070248A1 · Ichikawa · 2011 [cited by applicant]
US 20110212088A1 · Sabbadini · 2011 [cited by applicant]
US 20120213783A1 · Rosenberg · 2012 [cited by applicant]
US 20140112956A1 · Karlsson-Parra · 2014 [cited by applicant]
US 20140134720A1 · Stauss · 2014 [cited by applicant]
JP 2014514927 · 2014 [cited by applicant]
WO 0425235 · 1991 [cited by applicant]
WO WO2004010957 · 2004 [cited by applicant]
WO WO2006065495 · 2006 [cited by applicant]
WO WO2012079000 · 2012 [cited by applicant]
WO WO2013126726 · 2013 [cited by applicant]
WO WO2014082729 · 2014 [cited by applicant]
WO WO2014153270 · 2014 [cited by applicant]
WO WO2014186469 · 2014 [cited by applicant]
WO WO2015063069 · 2015 [cited by applicant]
WO WO2016201394 · 2016 [cited by applicant]
EP Extended Search Report in European Application. No. 20208043.8, dated Jun. 7, 2021, 6 pages. [cited by applicant]
Kyte et al., “T cell responses in melanoma patients after vaccination with tumor-mRNA transfected dendritic cells,” Cancer Immunology Immunotherapy, May 1, 2007, 56(5):659-675. [cited by applicant]
Abate-Daga, et al., “CAR models: next-generation CAR modifications for enhanced I-cell function,” Mol. Ther.—Oncolytics, 2016, pp. 1-7. [cited by applicant]
Ahmad et al., “scFv antibody: principles and clinical application,” Clin. Dev. Immunol., 2012, 980250, 15 pages. [cited by applicant]
Al-Lazikani et al., “Standard conformations for the canonical structures of immunoglobulins,” J. Mol. Biol., 1997, 273:927-948. [cited by applicant]
Bierer et al., “Cyclosporin A and FK506: molecular mechanisms of immunosuppression and probes for transplantation biology,” Curr. Opin. Immun., 1993, 5:763-773. [cited by applicant]
Bird et al., “Single-chain antigen-binding proteins,” Science, 1988, 242:423-426. [cited by applicant]
Brentjens et al., “Treatment of Chronic Lymphocytic Leukemia With Genetically Targeted Autologous T Cells: Case Report of an Unforeseen Adverse Event in a Phase I Clinical Trial,” Mol. Ther., 2010, 18(4):666-668. [cited by applicant]
Brown et al., “Stem-like tumor-initiating cells isolated from IL13Rα2 expressing gliomas are targeted and killed by IL13-zetakine-redirected T Cells,” Clin Cancer Res., 2012, 18(8):2199-2209. [cited by applicant]
Capecchi “High efficiency transformation by direct microinjection of DNA into cultured mammalian cells,” Cell, 1980, 22:479-488. [cited by applicant]
Clay et al., “Efficient Transfer of a Tumor Antigen-Reactive TCR to Human Peripheral Blood Lymphocytes Confers Anti-Tumor Reactivity,” J. Immunol, 1999, 163:507-513. [cited by applicant]
DeKosky et al., “In-depth determination and analysis of the human paired heavy- and light-chain antibody repertoire,” Nature Medicine, 2015, 21:86-91. [cited by applicant]
Di Stasi et al., “Inducible apoptosis as a safety switch for adoptive cell therapy,” N. Engl. J. Med., 2011, 365(18):1673-83. [cited by applicant]
Dotti et al., “Design and development of therapies using chimeric antigen receptor-expressing T cells,” Immunological Reviews, 2013, 257(1):107-126. [cited by applicant]
Dubowchik and Walker, “Receptor-mediated and enzyme-dependent targeting of cytotoxic anticancer drugs,” Pharmacol. Ther., 1999, 83:67-123. [cited by applicant]
Felgner et al., “Lipofection: a highly efficient, lipid-mediated DNA-transfection procedure,” Proc. Natl. Acad. Sci. USA, 1987, 84:7413-7417. [cited by applicant]
Foster et al., “Antitumor activity of EBV-specific T lymphocytes transduced with a dominant negative TGF-beta receptor,” J. Immunother., 2008, 31(5):500-5. [cited by applicant]
Funatsu et al., “The complete amino acid sequence of the A-chain of Abrin-a, a toxic protein from the seeds of Abrus precatorius,” Agr. Biol. Chem., 1988, 52:1095-1097. [cited by applicant]
Gallin, “Ionic channels in leukocytes,” J. Leukoc. Biol., 1986, 39:241-254. [cited by applicant]
GenBank: AAA35664.1, “T lymphocyte surface glycoprotein (CD8-beta) precursor [ [cited by applicant]
Gillespie et al., “Phase I open study of the effects of ascending doses of the cytotoxic immunoconjugate CMB-401 (hCTMO1-calicheamicin) in patients with epithelial ovarian cancer,” Ann. Oncol., 2000, 11:735-741. [cited by applicant]
Goyal and Batra, “Inclusion of a furin-sensitive spacer enhances the cytotoxicity of ribotoxin restrictocin containing recombinant single-chain immunotoxins,” Biochem., 2000, 345 Pt 2:247-254. [cited by applicant]
Graham et al., “A new technique for the assay of infectivity of human adenovirus 5 DNA,” Virology, 1973, 52:456-467. [cited by applicant]
Grupp et al., “Chimeric Antigen Receptor-Modified T Cells for Acute Lymphoid Leukemia,” N. Engl., J. Med., 2013, 368:1509-1518. [cited by applicant]
Hamers-Casterman et al., “Naturally occurring antibodies devoid of light chains,” Nature, 1993, 363:446-448. [cited by applicant]
Han et al., “Chimeric antigen receptor-engineered T cells for cancer immunotherapy: progress and challenges,” J. Hematol. Oncol, 2013, 6:47, 7 pages. [cited by applicant]
Han et al., “Linking T-cell receptor sequence to functional phenotype at the single-cell level,” Nature Biotechnology, 2014, 32:684-692. [cited by applicant]
Haso et al., “Anti-CD22-chimeric antigen receptors targeting B cell precursor acute lymphoblastic leukemia,” Blood, 2013, 121(7):1165-74. [cited by applicant]
Hegde et al., “Combinational targeting offsets antigen escape and enhances effector functions of adoptively transferred T cells in glioblastoma,” Mol. Ther., 2013, 21(11):2087-2101. [cited by applicant]
Henderson et al., “Comparison of the effects of FK-506, cyclosporin A and rapamycin on IL-2 production,” Immunol., 1991, 73:316-321. [cited by applicant]
Holliger et al., ““Diabodies”: small bivalent and bispecific antibody fragments,” Proc. Natl. Acad. Sci., 1993, 90:6444 6448. [cited by applicant]
Huse et al., “Generation of a large combinatorial library of the immunoglobulin repertoire in phage lambda,” Science, 1989, 246:1275-1281. [cited by applicant]
Huston et al., “Protein engineering of antibody binding sites: recovery of specific activity in an anti-digoxin single-chain Fv analogue produced in [cited by applicant]
Ijntema et al., “Hydroxyapatite microcarriers for biocontrolled release of protein drugs,” Int. J. Pharm., 1994, 112:215-224. [cited by applicant]
International Search Report and Written Opinion in PCT Application. No. PCT/US2016/037120, dated Oct. 31, 2016. [cited by applicant]
Johnston, et al., “Sustained Delivery of Interleukin-2 from a Poloxamer 407 Gel Matrix Following Intraperitoneal Injection in Mice,” Pharm. Res., 1992, 9:425-434. [cited by applicant]
Jurgens et al., “Transduction of primary lymphocytes with Epstein-Barr virus (EBV) latent membrane protein-specific T cell receptor induces lysis of virus-infected cells: a novel strategy for the treatment of Hodgkin's … [cited by applicant]
Klein et al., “High-velocity microprojectiles for delivering nucleic acids into living cells,” Nature, 1987, 327:70-73. [cited by applicant]
Kloss et al., “Combinatorial antigen recognition with balanced signaling promotes selective tumor eradication by engineered T cells,” Nat. Biotechnol., 2013, 31(1):71-5. [cited by applicant]
Kochenderfer et al., “B-cell depletion and remissions of malignancy along with cytokine-associated toxicity in a clinical trial of anti-CD19 chimeric-antigen-receptor-transduced T cells,” Blood, 2012, 119(12):2709-20. [cited by applicant]
Laird and Groman, “Isolation and characterization of tox mutants of corynebacteriophage beta,” J. Virol., 1976, 19:220-227. [cited by applicant]
Langer, “Polymer-controlled drug delivery systems,” Acc. Chem. Res., 1993, 26:537-542. [cited by applicant]
Lanitis et al., “Chimeric antigen receptor T Cells with dissociated signaling domains exhibit focused antitumor activity with reduced potential for toxicity in vivo,” Cancer Immunol. Res., 2013, 1(1):43-53. [cited by applicant]
Lau et al., “Conjugation of doxorubicin to monoclonal anti-carcinoembryonic antigen antibody via novel thiol-directed cross-linking reagents,” Bioorg-Med-Chem., 1995, 3(10):1299-1304. [cited by applicant]
Lau et al., “Novel doxorubicin-monoclonal anti-carcinoembryonic antigen antibody immunoconjugate activity in vitro,” Bioorg-Med-Chem., 1995, 3(10):1305-12. [cited by applicant]
Lee et al., “Calicheamicins, a novel family of antitumor antibiotics,” J. Antibiot., 1989, 42:1070-87. [cited by applicant]
Lefranc et al., “IMGT unique numbering for immunoglobulin and T cell receptor variable domains and lg superfamily V-like domains,” Dev. Comp. Immunol., 2003, 27:55-77. [cited by applicant]
Lehner et al., “Redirecting T Cells to Ewing's Sarcoma Family of Tumors by a Chimeric NKG2D Receptor Expressed by Lentiviral Transduction or mRNA Transfection,” PLoS One. 2012, 7(2):e31210. [cited by applicant]
Liechtenstein et al., “Lentiviral vectors for cancer immunotherapy and clinical applications,” Cancers (Basel), 2013, 5:815-837. [cited by applicant]
Liepins et al., “Serotonin modulated Ca++ dependent K+ channels in alloimmune effector cell lytic function,” Immunopharmacol. Immunotoxicol., 1989, 11:165-178. [cited by applicant]
Liu et al., “Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes,” Cell, 1991, 66:807-815. [cited by applicant]
Lonberg, “Fully human antibodies from transgenic mouse and phage display platforms,” Curr. Opin. Immunol., 2008, 20:450-459. [cited by applicant]
Lonberg, “Human antibodies from transgenic animals,” Nat. Biotech., 2005, 23:1117-1125. [cited by applicant]
Long et al., “Lessons learned from a highly-active CD22-specific chimeric antigen receptor,” Oncoimmunology, 2013, 2(4):e23621. [cited by applicant]
Milone et al., “Chimeric receptors containing CD137 signal transduction domains mediate enhanced survival of T cells and increased antileukemic efficacy in vivo,” Mol. Ther., 2009, 17(8):1453-1464. [cited by applicant]
Morgan et al., “Case Report of a Serious Adverse Event Following the Administration of T Cells Transduced With a Chimeric Antigen Receptor Recognizing ERBB2,” Molecular Therapy, 2010, 18(4):843-851. [cited by applicant]
NCBI RefSeq: NP_000064.1, “T-cell surface glycoprotein CD3 gamma chain precursor [ [cited by applicant]
NCBI RefSeq: NP_000130.1, “high affinity immunoglobulin epsilon receptor subunit beta isoform 1 [ [cited by applicant]
NCBI RefSeq: NP_000607.1, “T-cell surface glycoprotein CD4 isoform 1 precursor [ [cited by applicant]
NCBI RefSeq: NP_000617.1, “B-cell antigen receptor complex-associated protein beta chain isoform 1 precursor [ [cited by applicant]
NCBI RefSeq: NP_000723.1, “T-cell surface glycoprotein CD3 delta chain isoform A precursor [ [cited by applicant]
NCBI RefSeq: NP_000724.1, “T-cell surface glycoprotein CD3 epsilon chain precursor [ [cited by applicant]
NCBI RefSeq: NP_001552.2, “tumor necrosis factor receptor superfamily member 9 precursor [ [cited by applicant]
NCBI RefSeq: NP_001758.2, “T-cell surface antigen CD2 precursor [ [cited by applicant]
NCBI RefSeq: NP_001759.3, “T-cell surface glycoprotein CD8 alpha chain isoform 1 precursor [ [cited by applicant]
NCBI RefSeq: NP_001762.2, “B-cell receptor CD22 isoform 1 precursor [ [cited by applicant]
NCBI RefSeq: NP_001774.1, “B-cell antigen receptor complex-associated protein alpha chain isoform 1 precursor [ [cited by applicant]
NCBI RefSeq: NP_001806.2, “carcinoembryonic antigen-related cell adhesion molecule 3 isoform 1 precursor [ [cited by applicant]
NCBI RefSeq: NP_003318.1, “tumor necrosis factor receptor superfamily member 4 precursor [ [cited by applicant]
NCBI RefSeq: NP_004097.1, “high affinity immunoglobulin epsilon receptor subunit gamma precursor [ [cited by applicant]
NCBI RefSeq: NP_006130.1, “T-cell-specific surface glycoprotein CD28 isoform 1 precursor [ [cited by applicant]
NCBI RefSeq: NP_036224.1, “inducible T-cell costimulator precursor [ [cited by applicant]
NCBI RefSeq: NP_055022.2, “T-cell surface glycoprotein CD5 precursor [ [cited by applicant]
NCBI RefSeq: NP_932170.1, “T-cell surface glycoprotein CD3 zeta chain isoform 1 precursor [ [cited by applicant]
Neville et al., “Enhancement of immunotoxin efficacy by acid-cleavable cross-linking agents utilizing diphtheria toxin and toxin mutants,” J. Biol. Chem., 1989, 264:14653-14661. [cited by applicant]
Nicolson & Blaustein, “The interaction of Ricinus communis agglutinin with normal and tumor cell surfaces,” J. Biochim. Biophys. Acta, 1972, 266:543-547. [cited by applicant]
Olsnes, “Ricin and ricinus agglutinin, toxic lectins from castor bean,” Methods Enzymol., 1978, 50:330-335. [cited by applicant]
Olsnes et al., “Mechanism of action of the toxic lectins abrin and ricin,” Nature, 1974, 249:627-631. [cited by applicant]
Orentas et al., “Retroviral transduction of a T cell receptor specific for an Epstein-Barr virus-encoded peptide,” Clinical Immunology, 2001, 98:220-228. [cited by applicant]
Park et al., “Treating cancer with genetically engineered T cells,” Trends Biotechnol., 2011, 29:550-557. [cited by applicant]
Phillips et al., “Targeting HER2-Positive Breast Cancer with Trastuzumab-DM1, an Antibody-Cytotoxic Drug Conjugate,” Cancer Res., 2008, 68:9280-9290. [cited by applicant]
Poljak et al., “Production and structure of diabodies,” Structure, 1994, 2:1121-1123. [cited by applicant]
Porter et al., “Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia,” N. Engl. J. Med., 2011, 365(8):725-33. [cited by applicant]
Rathore et al., “Overproduction of fungal ribotoxin α-sarcin in [cited by applicant]
Sheriff et al., “Redefining the minimal antigen-binding fragment,” Nat. Struct. Biol., 1996, 3:733-736. [cited by applicant]
Stirpe et al., “Ribosome—Inactivating Proteins from Plants: Present Status and Future Prospects,” Bio/Technology, 1992, 10:405-412. [cited by applicant]
Sun et al., “Unbiased analysis of TCRA/B chains at the single-cell level in human CD8+ T-Cell subsets,” PLoS ONE, 2012, 7:e40386. [cited by applicant]
Supplemental European Search Report for EP application. No. 16808492, dated Nov. 8, 2018. [cited by applicant]
Suzuki et al., “Engineering receptor-mediated cytotoxicity into human ribonucleases by steric blockade of inhibitor interaction,” Nat. Biotech., 1999, 17:265-70. [cited by applicant]
Thorpe et al., “New coupling agents for the synthesis of immunotoxins containing a hindered disulfide bond with improved stability in vivo,” Cancer Res., 1987, 47:5924-5931. [cited by applicant]
Till et al., “Adoptive immunotherapy for indolent non-Hodgkin lymphoma and mantle cell lymphoma using genetically modified autologous CD20-specific T cells,” Blood, 2008, 112:2261-2271. [cited by applicant]
Tumaini et al., “Simplified process for the production of anti-CD19-CAR-engineered T cells,” Cytotherapy, 2013, 15(11):1406-1417. [cited by applicant]
Ward et al., “Binding activities of a repertoire of single immunoglobulin variable domains secreted from [cited by applicant]
Winter and Harris, “Humanized antibodies,” Immunol. Today, 1993, 14:243-246. [cited by applicant]
Yu et al., “The biosynthetic gene cluster of the maytansinoid antitumor agent ansamitocin from Actinosynnema pretiosum,” PNAS, 2002, 99:7968-7973. [cited by applicant]
Yvon et al., “Immunotherapy of metastatic melanoma using genetically engineered GD2-specific T cells,” Clin. Cancer Res., 2009, 15(18):5852-60. [cited by applicant]
Zhao et al., “A herceptin-based chimeric antigen receptor with modified signaling domains leads to enhanced survival of transduced T lymphocytes and antitumor activity,” J. Immunol., 2009, 183(9):5563-74. [cited by applicant]
Zhao et al., “Primary Human Lymphocytes Transduced with NY-ESO-1 Antigen-Specific TCR Genes Recognize and Kill Diverse Human Tumor Cell Lines,” J. Immunol., 2005, 174:4415-4423. [cited by applicant]
EP Notice of Opposition European Application. No. 16808492.9, dated Aug. 20, 2021, 38 pages. [cited by applicant]
EPO Responsive to the Communication Pursuant to Rule 71(3) EPC / Prosecution in European Application. No. EP16808492.9, dated Sep. 8, 2020, 25 pages. [cited by applicant]
Karpanen et al., “T-cell receptor gene therapy—ready to go viral?,” Molecular Oncology, Dec. 1, 2015, 9(10):2019-42. [cited by applicant]
PCT Request in International Proceedings, Replacement Sheet, in PCT Application. No. PCT/US2016/037120, dated Dec. 6, 2016, (document submitted in opposition proceedings of EP 3 307 877 on Aug. 20, 2021), 1 page. [cited by applicant]
PCT Statement Accompanying Sequence Listing in International Proceedings Regarding the Sequence Listing Only for Purposes of International Search (Rule 13ter PCT), dated Jul. 18, 2016, (document submitted in opposition … [cited by applicant]
Schmitt et al., “New strategies in engineering T-cell receptor gene-modified T cells to more effectively target malignancies,” Clinical Cancer Research, Dec. 1, 2015, 21(23):5191-7. [cited by applicant]
GenBank ADM64594.1, “FMC63-28Z receptor protein [synthetic construct],” dated Jun. 11, 2012, 2 pages. [cited by applicant]
Simon et al., “Functional TCR retrieval from single antigen-specific human T cells reveals multiple novel epitopes,” Cancer Immunology Research, Dec. 1, 2014, 2(12):1230-1244. [cited by applicant]
Extended European Search Report in European Appln. No. 23188817.3, mailed on Feb. 6, 2024, 9 pages. [cited by applicant]