IP Library › Granted Patent US 12,296,010
Granted Patent B2
US 12,296,010 · App. 18/983,137 · Granted May 13, 2025

Methods for isolating, culturing, and genetically engineering immune cell populations for adoptive therapy

Inventors: Chris Ramsborg (Seattle, WA); Mark L. Bonyhadi (Sammamish, WA); Calvin Chan (Seattle, WA); Pascal Beauchesne (Seattle, WA)
Assignee: Juno Therapeutics, Inc.
A61K40/31A61K40/11A61K40/42A61K40/4211C12N5/0636C12N5/10A61K2035/124
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,296,010
App. No.
18/983,137
Granted
May 13, 2025
Kind
B2
Abstract

The present disclosure relates in some aspects to methods, cells, and compositions for preparing cells and compositions for genetic engineering and cell therapy. Provided in some embodiments are streamlined cell preparation methods, e.g., for isolation, processing, incubation, and genetic engineering of cells and populations of cells. Also provided are cells and compositions produced by the methods and methods of their use. The cells can include immune cells, such as T cells, and generally include a plurality of isolated T cell populations or types. In some aspects, the methods are capable of preparing of a plurality of different cell populations for adoptive therapy using fewer steps and/or resources and/or reduced handling compared with other methods.

Claims (26)

1. A method of treating systemic lupus erythematosus (SLE) in a human subject, the method comprising intravenously administering a dose of genetically engineered CD4+ and CD8+ T cells to a human subject with SLE, wherein:

the CD4+ and CD8+ T cells of the dose are at a ratio, wherein the ratio is between at or about 5:1 and at or about 1:3;

the dose of genetically engineered CD4+ and CD8+ T cells is between at or about 5×10 6 to 500×10 6 cells; and

the CD4+ and CD8+ T cells are genetically engineered with a chimeric antigen receptor (CAR), wherein the CAR comprises an scFv that binds CD19, a transmembrane domain, and an intracellular signaling domain comprising a 4-1BB costimulatory signaling domain and a CD3zeta signaling domain.

2. A method of treating systemic lupus erythematosus (SLE) in a human subject, the method comprising intravenously administering a dose of genetically engineered CD4+ and CD8+ T cells to a human subject with SLE, wherein:

the CD4+ and CD8+ T cells of the dose are at a ratio, wherein the ratio is between at or about 5:1 and at or about 1:3;

the dose of genetically engineered CD4+ and CD8+ T cells is between at or about 5×10 6 to 500×10 6 cells; and

the CD4+ and CD8+ T cells are genetically engineered with a chimeric antigen receptor (CAR), wherein the CAR comprises an scFv that binds CD19, a transmembrane domain, and an intracellular signaling domain comprising a CD28 costimulatory signaling domain and a CD3zeta signaling domain.

3. The method of claim 1 , wherein the dose of CD4+ and CD8+ T cells is between at or about 5×10 6 to 25×10 6 cells.

4. The method of claim 1 , wherein the dose of CD4+ and CD8+ T cells is at or about 5×10 6 cells.

5. The method of claim 1 , wherein the dose of CD4+ and CD8+ T cells is at or about 10×10 6 cells.

6. The method of claim 1 , wherein the dose of CD4+ and CD8+ T cells is between 20×10 6 cells and 60×10 6 cells.

7. The method of claim 1 , wherein the dose of CD4+ and CD8+ T cells is between 20×10 6 cells and 90×10 6 cells.

8. The method of claim 1 , wherein the dose of CD4+ and CD8+ T cells is between 20×10 6 cells and 250×10 6 cells.

9. The method of claim 1 , wherein the dose of CD4+ and CD8+ T cells is between 30×10 6 cells and 90×10 6 cells.

10. The method of claim 1 , wherein the percentage of CD4+ and CD8+ T cells in the dose is at least about 90%.

11. The method of claim 8 , wherein the percentage of CD4+ and CD8+ T cells in the dose is at least about 90%.

12. The method of claim 2 , wherein the dose of CD4+ and CD8+ T cells is between at or about 5×10 6 to 25×10 6 cells.

13. The method of claim 2 , wherein the dose of CD4+ and CD8+ T cells is at or about 5×10 6 cells.

14. The method of claim 2 , wherein the dose of CD4+ and CD8+ T cells is at or about 10×10 6 cells.

15. The method of claim 2 , wherein the dose of CD4+ and CD8+ T cells is between 20×10 6 cells and 60×10 6 cells.

16. The method of claim 2 , wherein the dose of CD4+ and CD8+ T cells is between 20×10 6 cells and 90×10 6 cells.

17. The method of claim 2 , wherein the dose of CD4+ and CD8+ T cells is between 20×10 6 cells and 250×10 6 cells.

18. The method of claim 2 , wherein the dose of CD4+ and CD8+ T cells is between 30×10 6 cells and 90×10 6 cells.

19. The method of claim 2 , wherein the percentage of CD4+ and CD8+ T cells in the dose is at least about 90%.

20. The method of claim 17 , wherein the percentage of CD4+ and CD8+ T cells in the dose is at least about 90%.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 31, 2025
From: RAMSBORG, CHRIS; BONYHADI, MARK L.; CHAN, CALVIN; BEAUCHESNE, PASCAL
To: JUNO THERAPEUTICS, INC.
Reel/Frame 070687/0387 →
Continuity (5)
Continuation 18166447 · Feb 8, 2023
Continuation 17850875 · Jun 27, 2022
Continuation 15305337
Provisional Application 61983415 · Apr 23, 2014
Related Publication 20250121062A1 · Apr 17, 2025
References Cited (400)
US 4235871A · Papahadjopoulos · 1980 [cited by applicant]
US 4361549A · Kung et al. · 1982 [cited by applicant]
US 4452773A · Molday · 1984 [cited by applicant]
US 4501728A · Geho · 1985 [cited by applicant]
US 4690915A · Rosenberg · 1987 [cited by applicant]
US 4795698A · Owen · 1989 [cited by applicant]
US 4835263A · Nguyen et al. · 1989 [cited by applicant]
US 4837028A · Allen · 1989 [cited by applicant]
US 5019369A · Presant · 1991 [cited by applicant]
US 5087616A · Myers · 1992 [cited by applicant]
US 5200084A · Liberti · 1993 [cited by applicant]
US 5219740A · Miller · 1993 [cited by applicant]
US 5506121A · Skerra · 1996 [cited by applicant]
US 5736137A · Anderson et al. · 1998 [cited by applicant]
US 5773224A · Grandics et al. · 1998 [cited by applicant]
US 5801115A · Albers et al. · 1998 [cited by applicant]
US 5985658A · Colinas et al. · 1999 [cited by applicant]
US 6022951A · Sano et al. · 2000 [cited by applicant]
US 6103493A · Skerra · 2000 [cited by applicant]
US 6207453B1 · Maass · 2001 [cited by applicant]
US 6352694B1 · June et al. · 2002 [cited by applicant]
US 6410319B1 · Raubitschek · 2002 [cited by applicant]
US 6451995B1 · Cheung · 2002 [cited by applicant]
US 7109304B2 · Hansen · 2006 [cited by applicant]
US 7446179B2 · Jensen · 2008 [cited by applicant]
US 7446190B2 · Sadelain · 2008 [cited by applicant]
US 7482000B2 · DeVaux · 2009 [cited by applicant]
US 7837871B2 · Gjerde et al. · 2010 [cited by applicant]
US 7981632B2 · Schmidt · 2011 [cited by applicant]
US 8389282B2 · Sadelain et al. · 2013 [cited by applicant]
US 8911993B2 · June et al. · 2014 [cited by applicant]
US 9023604B2 · Schmidt et al. · 2015 [cited by applicant]
US 9539251B2 · Sampath et al. · 2017 [cited by applicant]
US 9599590B2 · Sabin et al. · 2017 [cited by applicant]
US 10228312B2 · Stadler et al. · 2019 [cited by applicant]
US 10428351B2 · Crisman et al. · 2019 [cited by applicant]
US 11400115B2 · Ramsborg · 2022 [cited by examiner]
US 12208137B2 · Ramsborg · 2025 [cited by examiner]
US 20020131960A1 · Sadelain · 2002 [cited by applicant]
US 20030170238A1 · Gruenberg · 2003 [cited by applicant]
US 20030175850A1 · Ross et al. · 2003 [cited by applicant]
US 20040043401A1 · Sadelain · 2004 [cited by applicant]
US 20040082012A1 · Busch · 2004 [cited by applicant]
US 20040126363A1 · Jensen · 2004 [cited by applicant]
US 20040167319A1 · Teeling et al. · 2004 [cited by applicant]
US 20060019319A1 · Billadeau et al. · 2006 [cited by applicant]
US 20060106199A1 · Erdmann et al. · 2006 [cited by applicant]
US 20070116690A1 · Yang et al. · 2007 [cited by applicant]
US 20070241061A1 · Engstrom et al. · 2007 [cited by applicant]
US 20080085532A1 · Gorlach et al. · 2008 [cited by applicant]
US 20080131415A1 · Riddell · 2008 [cited by applicant]
US 20080255004A1 · Neurauter et al. · 2008 [cited by applicant]
US 20090035322A1 · Martin et al. · 2009 [cited by applicant]
US 20100068738A1 · Kawamura et al. · 2010 [cited by applicant]
US 20100104509A1 · King et al. · 2010 [cited by applicant]
US 20110003380A1 · Miltenyi · 2011 [cited by applicant]
US 20110070581A1 · Gupta · 2011 [cited by applicant]
US 20130287748A1 · June · 2013 [cited by applicant]
US 20140255993A1 · Follstad et al. · 2014 [cited by applicant]
US 20140314795A1 · Riddell · 2014 [cited by applicant]
US 20140356398A1 · Riddell · 2014 [cited by applicant]
US 20150024411A1 · Stadler · 2015 [cited by applicant]
US 20150283178A1 · June et al. · 2015 [cited by applicant]
US 20150301046A1 · Schmidt · 2015 [cited by applicant]
US 20150306141A1 · Jensen · 2015 [cited by applicant]
US 20160045551A1 · Brentjens · 2016 [cited by applicant]
US 20160220656A1 · Godart · 2016 [cited by applicant]
US 20160362472A1 · Bitter et al. · 2016 [cited by applicant]
US 20170037370A1 · Kaiser et al. · 2017 [cited by applicant]
US 20170051252A1 · Morgan et al. · 2017 [cited by applicant]
US 20170209492A1 · June et al. · 2017 [cited by applicant]
US 20170240882A1 · Abrams et al. · 2017 [cited by applicant]
US 20170254774A1 · Sabin et al. · 2017 [cited by applicant]
US 20180064627A1 · Lange et al. · 2018 [cited by applicant]
US 20180296602A1 · Riddell et al. · 2018 [cited by applicant]
US 20190226951A1 · Stadler et al. · 2019 [cited by applicant]
US 20190234844A1 · Stadler et al. · 2019 [cited by applicant]
US 20200354677A1 · Lee et al. · 2020 [cited by applicant]
US 20200384025A1 · Mujacic et al. · 2020 [cited by applicant]
US 20210163893A1 · Westoby et al. · 2021 [cited by applicant]
US 20230087953A1 · Westoby et al. · 2023 [cited by applicant]
US 20230090176A1 · Ramsborg et al. · 2023 [cited by applicant]
US 20230190798A1 · Westoby et al. · 2023 [cited by applicant]
US 20230190814A1 · Ramsborg et al. · 2023 [cited by applicant]
US 20250020556A1 · Stadler · 2025 [cited by applicant]
CN 101226118 · 2008 [cited by applicant]
CN 103305464 · 2013 [cited by applicant]
CN 103502438 · 2014 [cited by applicant]
EP 0452342 · 1991 [cited by applicant]
EP 0700430 · 1996 [cited by applicant]
EP 2537416 · 2012 [cited by applicant]
EP 3346001 · 2018 [cited by applicant]
EP 3699268 · 2020 [cited by applicant]
WO WO1992008796 · 1992 [cited by applicant]
WO WO1994028143 · 1994 [cited by applicant]
WO WO2000014257 · 2000 [cited by applicant]
WO WO2000043551 · 2000 [cited by applicant]
WO WO2002054065 · 2002 [cited by applicant]
WO WO2002077018 · 2002 [cited by applicant]
WO WO2002077029 · 2002 [cited by applicant]
WO WO2004029221 · 2004 [cited by applicant]
WO WO2004096975 · 2004 [cited by applicant]
WO WO2005050209 · 2005 [cited by applicant]
WO WO2006044650 · 2006 [cited by applicant]
WO WO2006060878 · 2006 [cited by applicant]
WO WO2006130458 · 2006 [cited by applicant]
WO WO2007112012 · 2007 [cited by applicant]
WO WO2007117602 · 2007 [cited by applicant]
WO WO2008011486 · 2008 [cited by applicant]
WO WO2008140573 · 2008 [cited by applicant]
WO WO2009003493 · 2009 [cited by applicant]
WO WO2009072003 · 2009 [cited by applicant]
WO WO2009072006 · 2009 [cited by applicant]
WO WO2009091826 · 2009 [cited by applicant]
WO WO2009092068 · 2009 [cited by applicant]
WO WO2009097119 · 2009 [cited by applicant]
WO WO2010033140 · 2010 [cited by applicant]
WO WO2011107489 · 2011 [cited by applicant]
WO WO2012017081 · 2012 [cited by applicant]
WO WO2012081650 · 2012 [cited by applicant]
WO WO2012129514 · 2012 [cited by applicant]
WO WO2013011011 · 2013 [cited by applicant]
WO WO2013038272 · 2013 [cited by applicant]
WO WO2013062365 · 2013 [cited by applicant]
WO WO2013123061 · 2013 [cited by applicant]
WO WO2013124474 · 2013 [cited by applicant]
WO WO2013126726 · 2013 [cited by applicant]
WO WO2014011996 · 2014 [cited by applicant]
WO WO2014031687 · 2014 [cited by applicant]
WO WO2014055668 · 2014 [cited by applicant]
WO WO2014076277 · 2014 [cited by applicant]
WO WO2014165707 · 2014 [cited by applicant]
WO WO2014186469 · 2014 [cited by applicant]
WO WO2015095895 · 2015 [cited by applicant]
WO WO2015157252 · 2015 [cited by applicant]
WO WO2015157384 · 2015 [cited by applicant]
WO WO2015157399 · 2015 [cited by applicant]
WO WO2015158868 · 2015 [cited by applicant]
WO WO2015162211 · 2015 [cited by applicant]
WO WO2015164594 · 2015 [cited by applicant]
WO WO2015164675 · 2015 [cited by applicant]
WO WO2015164745 · 2015 [cited by applicant]
WO WO2015168613 · 2015 [cited by applicant]
WO WO2016019300 · 2016 [cited by applicant]
WO WO2016033570 · 2016 [cited by applicant]
WO WO2016069282 · 2016 [cited by applicant]
WO WO2016069283 · 2016 [cited by applicant]
WO WO2016073602 · 2016 [cited by applicant]
WO WO2016090190 · 2016 [cited by applicant]
WO WO2016090369 · 2016 [cited by applicant]
WO WO2016094304 · 2016 [cited by applicant]
WO WO2016109410 · 2016 [cited by applicant]
WO WO2016164580 · 2016 [cited by applicant]
WO WO2017015427 · 2017 [cited by applicant]
WO WO2017015490 · 2017 [cited by applicant]
WO WO2017023803 · 2017 [cited by applicant]
WO WO2017027291 · 2017 [cited by applicant]
WO WO2017068421 · 2017 [cited by applicant]
WO WO2017096329 · 2017 [cited by applicant]
WO WO2017156479 · 2017 [cited by applicant]
WO WO2017157505 · 2017 [cited by applicant]
WO WO2017161353 · 2017 [cited by applicant]
WO WO2018106732 · 2018 [cited by applicant]
WO WO2018191723 · 2018 [cited by applicant]
WO WO2019089855 · 2019 [cited by applicant]
WO WO2019113557 · 2019 [cited by applicant]
WO WO2020033927 · 2020 [cited by applicant]
WO WO2021163389 · 2021 [cited by applicant]
WO WO2021163391 · 2021 [cited by applicant]
Katz et al. (2014) Leukemia & Lymphoma, vol. 55(5), 99-1006. [cited by examiner]
Jethwa et al. (2014) Clinical Immunology, vol. 150, 51-63. [cited by examiner]
Marcus et al. (2014) Exp. Opin. Biol. Ther., vol. 14:7, 947-954. [cited by examiner]
Mei et al. (2012) Arthritis Research & Therapy, vol. 14 (Suppl 5): S1, pp. 1-16. [cited by examiner]
U.S. Appl. No. 19/029,968, filed Jan. 17, 2025, by Ramsborg et al. [cited by applicant]
U.S. Appl. No. 19/030,019, filed Jan. 17, 2025, by Ramsborg et al. [cited by applicant]
U.S. Appl. No. 19/030,056, filed Jan. 17, 2025, by Ramsborg et al. [cited by applicant]
Actemra® [Prescribing Information]. South San Francisco, USA: Genentech Inc. Available from: URL: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/1252763092lbl.pdf. [cited by applicant]
Adams et al., “A pilot study: use of fludarabine for refractory dermatomyositis and polymyositis, and examination of endpoint measures.” The Journal of Rheumatology 26.2 (1999): 352-360. [cited by applicant]
Akron Biotech “Exceptional purity, consistency and performance. Expand T-Cells and NK-Cells with Akron's cGMP IL-15,” (Aug. 2023):1-9. [cited by applicant]
Aksoy et al., “Human primary T cells: A practical guide,” dated Jun. 19, 2018. Retrieved from https://peerj.com/preprints/26993.html. [cited by applicant]
Alarcon et al., “Effect of hydroxychloroquine on the survival of patients with systemic lupus erythematosus: data from Lumina, a multiethnic US cohort ( [cited by applicant]
Al-Shanti et al., “Human purified CD8+ T cells: Ex vivo expansion model to generate a maximum yield of functional cytotoxic cells,” Immunol Invest. (Jan. 2007) 36(1):85-104. [cited by applicant]
Alonso-Camino et al., “CARbodies: Human Antibodies Against Cell Surface Tumor Antigens Selected From Repertoires Displayed on T Cell Chimeric Antigen Receptors,” Mol Ther Nucl Acids (2013) 2: e93, 11 pages. [cited by applicant]
Amadori et al., “Genetic control of the CD4/CD8 T-cell ratio in humans,” Nature Med. (1995) 1: 1279-1283. [cited by applicant]
American Academy of Dermatology Ad Hoc Task Force for the ABCDEs of Melanoma et al., “Early detection of melanoma: reviewing the ABCDEs,” J Am Acad Dermatol (2015) 72(4):717-723. [cited by applicant]
Amos et al., “The role of caspase 3 and BclxL in the action of interleukin 7 (IL-7): a survival factor in activated human T cells,” Cytokine. (1998) 10(9):662-8. [cited by applicant]
Anonymous, “Scientists helping scientists™ | WWW Optimization of Human T Cell Expansion Protocol: Effects of Early Cell Dilution,” (2018). [cited by applicant]
“Antisynthetase-Syndrome,” Retrieved Jul. 26, 2024; Retrieved from https://understandingmyositis.org/myositis/antisynthetase-syndrome/. [cited by applicant]
Applikon Biotechnology/BioPharma-Reporter (2016) How automation has changed the way we count cells BioPharma-Reporter.com; 1-4 (Year: 2016). [cited by applicant]
Arbuckle et al., “Development of Autoantibodies before the Clinical Onset of Systemic Lupus Erythematosus,” N Engl J Med (2003) 349:1526-1533. [cited by applicant]
Arnett et al., “The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis,” Arthritis Rheum. (1988) 31(3):315-24. [cited by applicant]
Bachmann et al., “Functional Properties and Lineage Relationship of CD8+ T Cell Subsets Identified by Expression of IL-7 Receptor and CD62L,” J. Immunol. (2005) 175:4686-96. [cited by applicant]
Barrett et al., “The length and mode of termination of individual muscle fibers in the human Sartorius and posterior femoral muscles,” Cell Tissues Organs (1962) 48(3):242-257. [cited by applicant]
Baum et al., “Retrovirus vectors: toward the plentivirus?,” Molecular Therapy: The Journal of the American Society of Gene Therapy (2006) 13:1050-1063. [cited by applicant]
Bazzan et al., “Systemic lupus erythematosus and thrombosis,” Thromb J. (2015) 13:16. doi: 10.1186/s12959-015-0043-3. [cited by applicant]
Berger et al., “Adoptive transfer of effector CD8 T cells derived from central memory cells establishes persistent T cell memory in primates.” J Clin Invest (2008) 118(1): 294-305. [cited by applicant]
Bergmann et al., “6 Months-follow up Data of Systemic Sclerosis Patients Treated with CD 19 Targeting CAR-T Cells,” American College of Rheumatology, Meeting: ACR Convergence 2023, Session date: Wednesday, Nov. 15, 2023… [cited by applicant]
Berthois et al., “Phenol red in tissue culture media is a weak estrogen: Implications concerning the study of estrogen-responsive cells in culture,” Proc. Natl. Acad. Sci (1986) 83: 2496-2500. [cited by applicant]
Bes et al., “Mapping the paratope of anti-CD4 recombinant Fab 13B8.2 by combining parallel peptide synthesis and site-directed mutagenesis,” J. Biol. Chem. (2003) 278:14265-14273. [cited by applicant]
Bohan et al., “Polymyositis and Dermatomyositis: (Second of Two Parts),” New England Journal of Medicine (1975), 292.8, p. 403-407. [cited by applicant]
Bondanza et al., “IL-7 receptor expression identifies suicide gene-modified allospecific CD8+ T cells capable of self-renewal and differentiation into antileukemia effectors,” Blood. (Jun. 2011) 117(24):6469-6478. [cited by applicant]
Boris-Lawrie et al., “Recent advances in retrovirus vector technology,” Cur. Opin. Genet. Develop. (1993) 3:102-109. [cited by applicant]
Bostrom et al., “High Affinity Antigen Recognition of the Dual Specific Variants of Herceptin Is Entropy-Driven in Spite of Structural Plasticity,” PLOS One (2011) 6(4):e17887. [cited by applicant]
Boyman et al., “The role of interleukin-2 in memory CD8 cell differentiation,” Adv Exp Med Biol (2010) 684:28-41. [cited by applicant]
Brady et al., “HIV integration site distributions in resting and activated CD4+ T cells infected in culture,” AIDS. (2009) 23(12):1461-71. [cited by applicant]
Brash et al., “Strontium phosphate transfection of human cells in primary culture: stable expression of the simian virus 40 large-T-antigen gene in primary human bronchial epithelial cells,” Mol. Cell Biol. (1987) 7: 20… [cited by applicant]
Braun et al., “Rapid separation of T cell subpopulations with monoclonal antibodies and affinity chromatography,” J Immunological Methods (1982) 54:251-258. [cited by applicant]
Brentjens et al., “Safety and persistence of adoptively transferred autologous CD19-targeted T cells in patients with relapsed or chemotherapy refractory B-cell leukemias,” Blood (2011) 118(18):4817-4828. [cited by applicant]
Brentjens, R., “Dosing Strategies: Goals and Options” Slide Deck of Oral Presentation made at NIH T cell Immunotherapy—Optimizing Trial Design Symposium, Bethesda, MD (Sep. 10, 2013) 14 pages, Retrieved from the Interne… [cited by applicant]
Burns et al., “Vesicular stomatitis virus G glycoprotein pseudotyped retroviral vectors: concentration to very high titer and efficient gene transfer into mammalian and nonmammalian cells,” Proc. Natl. Acad. Sci. USA (1… [cited by applicant]
Burt et al., “Nonmyeloablative Hematopoietic Stem Cell Transplantation for Systemic Lupus Erythematosus,” JAMA (2006) 295(5):527-535. [cited by applicant]
Burt et al., “Hematopoietic stem cell transplantation for autoimmune diseases: What have we learned?” J Autoimmunity (2008) 30(3):116-120. [cited by applicant]
Butler et al., “Ex Vivo Expansion of Human CD8+ T Cells Using Autologous CD4+ T Cell Help,” PLoS ONE (2012) 7(1): e30229. [cited by applicant]
Caggiari et al., “Different rates of CD4+ and CD8+ T-cell proliferation in interleukin-2-treated human immunodeficiency virus-positive subjects,” Cytometry (2001) 46(4): 233-237. [cited by applicant]
Cambridge et al., “B cell depletion therapy in systemic lupus erythematosus: Effect on autoantibody and antimicrobial antibody profiles.” Arthritis Rheum. (2006) 54(11): 3612. [cited by applicant]
Cambridge et al., “B cell depletion therapy in systemic lupus erythematosus: relationships among serum B lymphocyte stimulator levels, autoantibody profile and clinical response,” Ann Rheum Dis. (2008) 67(7):1011-6. [cited by applicant]
Carlens et al., “Ex vivo T lymphocyte expansion for retroviral transduction: influence of serum-free media on variations in cell expansion rates and lymphocyte subset distribution,” Exp Hematol (2000) 28(10): 1137-1146. [cited by applicant]
Casalegno-Gardua et al., “Multimer technologies for detection and adoptive transfer of antigen-specific T cells,” Cancer Immunology (2009) 59(2):195-202. [cited by applicant]
Casati et al., “Clinical-scale selection and viral transduction of human naïve and central memory CD8+ T cells for adoptive cell therapy of cancer patients,” Cancer Immunology (2013) 62(10): 1563-1573. [cited by applicant]
Casati et al., “Enrichment, stimulation, and viral transduction of naive and central memory CD8+ T cells under GMP conditions for translational research towards the development of adoptive cell therapy of cancer patient… [cited by applicant]
Cattoglio et al., “Hot spots of retroviral integration in human CD34+ hematopoietic cells,” Blood. (2007) 110(6):1770-8. [cited by applicant]
Cavalieri et al., “Human T lymphocytes transduced by lentiviral vectors in the absence of TCR activation maintain an intact immune competence,” Blood (2003) 102(2): 497-505. [cited by applicant]
Cervera et al., “Morbidity and mortality in systemic lupus erythematosus during a 10-year period: a comparison of early and late manifestations in a cohort of 1,000 patients,” Medicine (Baltimore) (2003) 82(5):299-308. [cited by applicant]
Cervera et al., “Systemic lupus erythematosus: clinical and immunologic patterns of disease expression in a cohort of 1,000 patients. The European Working Party on Systemic Lupus Erythematosus,” Medicine (Baltimore). (1… [cited by applicant]
Chakravarti et al., “The CD4/CD8 ratio: message in a bottle?” Nature Med. (1995) 1:1240-1241. [cited by applicant]
Chang et al., “Investigation of interfacial properties of pure and mixed poloxamers for surfactant-mediated shear protection of mammalian cells,” Colloids Surf B Biointerfaces. (Aug. 2017) 156:358-365. [cited by applicant]
Chang et al., “Identification and selective expansion of functionally superior T cells expressing chimeric antigen receptors,” J Transl Med (2015) 13(1):161. [cited by applicant]
Chen et al., “CD8 T cells specific for human immunodeficiency virus, Epstein-Barr virus, and cytomegalovirus lack molecules for homing to lymphoid sites of infection,” Blood. (2001) 1;98(1):156-64. [cited by applicant]
Chicaybam et al., “An efficient low cost method for gene transfer to T lymphocytes,” PLoS ONE (2013) 8(3): e60298, 11 pages. [cited by applicant]
Cho et al., “Human mammalian cell sorting using a highly integrated micro-fabricated fluorescence-activated cell sorter (microFACS),” Lab Chip (2010) 10: 1567-1573. [cited by applicant]
Church et al., “Tumor-specific CD4+ T cells maintain effector and memory tumor-specific CD8+ T cells,” Eur J Immunol (2013) 44(1):69-79. [cited by applicant]
Clementi et al., “CD4 and CD8 T lymphocyte inheritance. Evidence for major autosomal recessive genes,” Hum. Genet. (1999) 105: 337-342. [cited by applicant]
Clinical Trial Study Record No. NCT00730639. “A Phase 1 Study of Nivolumab (BMS-936558) in Subjects With Advanced or Recurrent Malignancies (MDX1106-03),” First posted Oct. 30, 2008. Last updated Dec. 3, 2021. [cited by applicant]
Cohen et al., “Recognition of fresh human tumor by human peripheral blood lymphocytes transduced with a bicistronic retroviral vector encoding a murine anti-p53 TCR,” J Immunol. (2005) 175:5799-5808. [cited by applicant]
Coiffier et al., “Long-term outcome of patients in the LNH-98.5 trial, the first randomized study comparing rituximab-CHOP to standard CHOP chemotherapy in DLBCL patients: a study by the Groupe d'Etudes des Lymphomes de… [cited by applicant]
Cooper et al., “T-cell clones can be rendered specific for CD19: toward the selective augmentation of the graft-versus-B-lineage leukemia effect,” Blood. (2003) 101:1637-1644. [cited by applicant]
Corada et al., “Monoclonal antibodies directed to different regions of vascular endothelial cadherin extracellular domain affect adhesion and clustering of the protein and modulate endothelial permeability,” Blood (2001… [cited by applicant]
Cordeiro et al., “Treatment of inflammatory myopathies,” Postgrad Med J (2006) 82(969):417-424. [cited by applicant]
Corral-Gudino et al., “Overall survival, renal survival and relapse in patients with microscopic polyangiitis: a systematic review of current evidence,” Rheumatology (2011) 50(8):1414-1423. [cited by applicant]
Couzin et al., “Gene therapy. As Gelsinger case ends, gene therapy suffers another blow,” Science (2005) 307(5712):1028. [cited by applicant]
Dainiak et al., “Methods in Cell Separations.” Adv Biochem Eng Biotechnol. (2007) 106:1-18. [cited by applicant]
Davila et al., “CD19 CAR-targeted T cells induce long-term remission and B Cell Aplasia in an immunocompetent mouse model of B cell acute lymphoblastic leukemia,” PLoS ONE (2013) 8(4): e61338, 14 pages. [cited by applicant]
Davila et al., “How do CARs work?: Early insights from recent clinical studies targeting CD19,” Oncoimmunology (2012) 1(9):1577-1583. [cited by applicant]
Davis et al., “Assessment of a positive selection technique using an avidin column to isolate human peripheral blood T cell subsets,” J Immunol Methods. (1994) 175(2):247-57. [cited by applicant]
Dayal et al., “SLE/myositis overlap: are the manifestations of SLE different in overlap disease?” Lupus. (2002) 11(5):293-298. [cited by applicant]
Dilillo et al., “Maintenance of Long-Lived Plasma Cells and Serological Memory Despite Mature and Memory B Cell Depletion during CD20 Immunotherapy in Mice1,” J Immunol (2008) 180(1):361-371. [cited by applicant]
Donahue et al., “Helper virus induced T cell lymphoma in nonhuman primates after retroviral mediated gene transfer,” J Exp Med (1992) 176(4): 1125-1135. [cited by applicant]
Dong, Modern Biology, Beijing Institute of Technology Press, 1st edition, p. 328, Jul. 31, 2016 (Article in Chinese; English translation provided). [cited by applicant]
Dupont et al., “Comparative dose-responses of recombinant human IL-2 and IL-7 on STAT5 phosphorylation in CD4+FOXP3 cells versus regulatory T cells: A whole blood perspective,” Cytokine (2014) 69(1):146-149. [cited by applicant]
Eaker et al., “Concise review: guidance in developing commercializable autologous/patient-specific cell therapy manufacturing,” Stem Cells Transl Med. (2013) 2(11): 871-83. [cited by applicant]
Farge et al., “Autologous hematopoietic stem cell transplantation for autoimmune diseases: an observational study on 12 years' experience from the European Group for Blood and Marrow Transplantation Working Party on Aut… [cited by applicant]
Fernandes et al., “Kinetics of class II MHC expression on cytotoxic T cells generated by skin allograft,” Tissue Antigens. (1990) 36(3):93-9. [cited by applicant]
Finney et al., “Activation of resting human primary T cells with chimeric receptors: costimulation from CD28, inducible costimulator, CD134, and CD137 in series with signals from the TCR zeta chain,” J Immunol. (Jan. 20… [cited by applicant]
Foster et al., “Human CD62L-memory T cells are less responsive to alloantigen stimulation than CD62L+ naive T cells: potential for adoptive immunotherapy and allodepletion,” Blood (2004) 104(8):2403-09. [cited by applicant]
Foulds et al., “Cutting edge: CD4 and CD8 T cells are intrinsically different in their proliferative responses,” J Immunol. (2002) 168(4):1528-1532. [cited by applicant]
Fraietta et al., “Biomarkers of Response to Anti-CD19 Chimeric Antigen Receptor (CAR) T-Cell Therapy in Patients with Chronic Lymphocytic Leukemia,” Blood (Dec. 2016) 128(22):57. [cited by applicant]
Fransen et al., “The Disease Activity Score and the EULAR response criteria,” Clin Exp Rheumatol. (2005) 23(5 Suppl 39):S93-S99. [cited by applicant]
Frayer et al., “Mean Body Weight, Height, Waist Circumference, and Body Mass Index Among Adults: United States, 1999-2000 Through 2015-2016,” Natl Health Stat Report. (2018) (122):1-16. [cited by applicant]
Frecha et al., “Advances in the field of lentivector-based transduction of T and B lymphocytes for gene therapy,” Molecular Therapy: The Journal of the American Society of Gene Therapy (2010) 18:1748-1757. [cited by applicant]
Freedman et al., “Normal cellular counterparts of B cell chronic lymphocytic leukemia,” Blood. (1987) 70:418-427. [cited by applicant]
Gardner et al., “T cell Products of Defined CD4:CD8 Composition and Prescribed Levels of CD19CAR/Egfrt Transgene Expression Mediate Regression of Acute Lymphoblastic Leukemia in the Setting of Post-Allohsct Relapse,” Ab… [cited by applicant]
Gargett et al., “Different cytokine and stimulation conditions influence the expansion and immune phenotype of third-generation chimeric antigen receptor T cells specific for tumor antigen GD2,” Cythotherapy (2015) 17(4… [cited by applicant]
Gattinoni and Restifo, “Moving T memory stem cells to the clinic,” Blood (2013) 121(4):567-8. [cited by applicant]
Gattinoni L et al., “Acquisition of full effector function in vitro paradoxically impairs the in vivo antitumor efficacy of adoptively transferred CDS+ T cells,” J Clin Invest. (2005) 115(6):1616-26. [cited by applicant]
Gladman et al., “Systemic Lupus Erythematosus Disease Activity Index 2000,” J Rheumatol (2002) 29:288-291. [cited by applicant]
Godin et al., “Microfluidics and photonics for Bio-System-on-a-Chip: a review of advancements in technology towards a microfluidic flow cytometry chip,” J Biophoton. (2008) 1(5):355-376. [cited by applicant]
González et al., “Ethnicity in systemic lupus erythematosus (SLE): its influence on susceptibility and outcomes,” Lupus (Oct. 2013), vol. 22(12), p. 1214-1224. [cited by applicant]
Granit et al., “Safety and clinical activity of autologous RNA chimeric antigen receptor T-cell therapy in myasthenia gravis (MG-001): a prospective, multicentre, open-label, non-randomised phase 1b/2a study,” Lancet Ne… [cited by applicant]
Gratwohl et al., “Stem cell transplantation for autoimmune diseases,” Best Practice & Research Clinical Haematology (2001) 14(4):755-776. [cited by applicant]
Grossman et al., “Concomitant regulation of T-cell activation and homeostasis,” Nat Rev Immunol (2004) 4(5):387-395. [cited by applicant]
Grupp et al., “T Cells Engineered with a Chimeric Antigen Receptor (CAR) Targeting CD19 (CTL019) Have Long Term Persistence and Induce Durable Remissions in Children with Relapsed, Refractory All,” Blood (2014) 124 (21)… [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]
Gunzer et al., “Two-step negative enrichment of CD4+ and CD8+ T cells from murine spleen via nylon wool adherence and an optimized antibody cocktail,” J Immunol Methods. (2001) 258(1-2): 55-63. [cited by applicant]
Hacein-Bey-Abina et al., “LMO2-associated clonal T cell proliferation in two patients after gene therpay for SCID-X1,” Science (2003) 302(5644); 415-419. [cited by applicant]
Hackett et al., “A transposon and transposase system for human application,” Molecular Therapy: The Journal of the American Society of Gene Therapy (2010) 18:674-683. [cited by applicant]
Harris-Love et al., “Distribution and severity of weakness among patients with polymyositis, dermatomyositis and juvenile dermatomyositis,” Rheumatology (Oxford) (2009) 48(2):134-139. [cited by applicant]
Hay et al., “The Bilag index: a reliable and valid instrument for measuring clinical disease activity in systemic lupus erythematosus,” QJM: An International Journal of Medicine (1993) 86(7):447-458. [cited by applicant]
Herbst et al., “B-cell depletion in vitro and in vivo with an afucosylated anti-CD19 antibody,” J Pharmacol Exp Ther. (2010) 335(1):213-22. [cited by applicant]
Hermans et al., “The Vital assay: a versatile fluorometric technique for assessing CTL- and NKT-mediated cytotoxicity against multiple targets in vitro and in vivo,” J. Immunological Methods (2004) 285(1): 25-40. [cited by applicant]
Hinchcliff et al., “J. Systemic sclerosis/scleroderma: a treatable multisystem disease,” American family physician. (2008) 78(8):961-8. [cited by applicant]
Hinrichs et al., “Human effector CD8+ T cells derived from naïve rather than memory subsets possess superior traits for adoptive immunotherapy,” Blood (2011) 117(3): 808-814. [cited by applicant]
Hinrichs et al., “Adoptively transferred effector cells derived from naive rather than central memory CD8+ T cells mediate superior antitumor immunity,” Proc Natl Acad Sci U S A. (2009) 106(41):17469-74. [cited by applicant]
Hirakawa et al., “IL-2, IL-7, IL-15 and IL-6 Induce Differential Activation of Naive and Memory T Cell Subsets,” Blood (Dec. 2015) 126(23):3425, 4 pages. [cited by applicant]
Hoffman, et al., “Differential modulation of CD4 and CD8 T-cell proliferation by induction of nitric oxide synthesis in antigen presenting cells,” Transplantation. (2002) 74(6): 836-845. [cited by applicant]
Hou et al., Tutorial on Animal Cell Culture Techniques, Gansu Science and Technology Press, Sep. 2009: p. 105 (Article in Chinese; English translation provided). [cited by applicant]
Huang et al., “DNA transposons for modification of human primary T lymphocytes,” Methods Mol Biol (2009) 506: 115-126. [cited by applicant]
Huarte et al., “Ex vivo expansion of tumor specific lymphocytes with IL-15 and IL-21 for adoptive immunotherapy in melanoma,” Cancer Lett. (2009) 285(1): 80-88. [cited by applicant]
Hudecek et al., “Direct tumour recognition and helper function of CD4+ T cells modified to express a CD19-specific CAR in vitro and in a preclinical lymphoma model,” Abstract for Presentation, 39th Annual Meeting of the… [cited by applicant]
Hudson et al., “Engineered Antibodies,” Nature Medicine (2003) 9(1):129-134. [cited by applicant]
Hunziker et al., “Exhaustion of cytotoxic T cells during adoptive immunotherapy of virus carrier mice can be prevented by B cells or CD4+ T cells,” Eur J Immunol (2002) 32(2):374-382. [cited by applicant]
Illei et al., “Long-term effects of combination treatment with fludarabine and low-dose pulse cyclophosphamide in patients with lupus nephritis.” (2007): 952-956. [cited by applicant]
ICell Gene Therapeutics, “Our Pipeline; iCell Gene Therapeutics researches and develops Chimeric Antigen Receptor (CAR) engineered cell therapies for autoimmune diseases and cancer,” Retrieved Jul. 26, 2024; From: https… [cited by applicant]
Imadome, “The clinical condition and diagnosis of EBV-T/NK-LPD (CAEBV, EBV-HLH etc.),” [Rinsho Ketsueki] Japanese J Clin Hematol (2013) 54(10):1992-98. (Reference in Japanese) English translation provided. [cited by applicant]
Isenberg et al., “Bilag 2004. Development and initial validation of an updated version of the British Isles Lupus Assessment Group's disease activity index for patients with systemic lupus erythematosus,” Rheumatology (… [cited by applicant]
Jackson et al., “Evaluation of CD62L expression as a marker for vaccine-elicited memory cytotoxic T lymphocytes,” Immunology (2005) 116, 443-53. [cited by applicant]
Jackson et al., “Levels of L-Selectin (CD62L) on Human Leukocytes in Disseminated Cryptococcosis With and Without Associated HIV-1 Infection,” J. Inf. Diseases (2005) 191:1361-7. [cited by applicant]
Janas et al., “Perfusion's role in maintenance of high-density T-cell cultures,” BioProcesses International. (2015) pp. 1-12. [cited by applicant]
Jethwa et al., “Use of gene-modified regulatory T-cells to control autoimmune and alloimmune pathology: is now the right time?,” Clin Immunol. (2014) 150(1):51-63. [cited by applicant]
Jiang Bo, Fundamentals and Clinics of Apoptosis, People's Military Medical Press, p. 141, Jul. 1999 (Reference in Chinese; English translation provided). [cited by applicant]
Johnston, et al., “Biolistic transformation: microbes to mice,” Nature (1990) 346: 776-777. [cited by applicant]
Kaartinen et al., “Low interleukin-2 concentration favors generation of early memory T cells over effector phenotypes during chimeric antigen receptor T-cell expansion,” Cytotherapy. (Jun. 2017) 19(6):689-702. [cited by applicant]
Kahn et al., “Optimization of retroviral vector-mediated gene transfer into endothelial cells in vitro,” Circ Res. (1992) 71(6): 1508-17. [cited by applicant]
Kamburova et al., “A Single Dose of Rituximab Does Not Deplete B Cells in Secondary Lymphoid Organs but Alters Phenotype and Function,” American Journal of Transplantation (2013) 13:1503-1511. [cited by applicant]
Kansal et al., “Sustained B cell depletion by CD19-targeted CAR T cells is a highly effective treatment for murine lupus,” Sci Transl Med. (2019) 11(482):eaav1648, 13 pages. [cited by applicant]
Kansas et al., “Transmembrane signals generated through MHC class II, CD19, CD20, CD39, and CD40 antigens induce LFA-1-dependent and independent adhesion in human B cells through a tyrosine kinase-dependent pathway,” J … [cited by applicant]
Katz et al., “Therapeutic targeting of CD19 in hematological malignancies: past, present, future and beyond.” Leuk Lymphoma. (2014) 55(5):999-1006. [cited by applicant]
Kemper et al., “Label-free quantitative cell division monitoring of endothelial cells by digital holographic microscopy,” J Biomed Opt. (May 2010) 15(3):036009, 6 pages. [cited by applicant]
Kiryluk et al., “Geographic Differences in Genetic Susceptibility to IgA Nephropathy: GWAS Replication Study and Geospatial Risk Analysis,” PLOS Genetics (2012) 8(6):e1002765. [cited by applicant]
Klaver et al., “T Cell Maturation Stage Prior to and During GMP Processing Informs on CAR T Cell Expansion in Patients,” Front Immunol. (Dec. 2016) 7:648. [cited by applicant]
Klebanoff et al., “Sorting through subsets: which T-cell populations mediate highly effective adoptive immunotherapy?,” J Immunother. (2012) 35(9): 651-660. [cited by applicant]
Klebanoff et al., “Sinks, suppressors and antigen presenters: how lymphodepletion enhances T cell-mediated tumor immunotherapy,” Trends Immunol. (2005) 26(2):111-7. [cited by applicant]
Klebanoff et al., “Central memory self/tumor-reactive CD8+ T cells confer superior antitumor immunity compared with effector memory T cells,” Proc Natl Acad Sci U S A. (2005); 102(27): 9571-6. [cited by applicant]
Kochenderfer 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 Clin … [cited by applicant]
Kochenderfer et al., “Construction and preclinical evaluation of an anti-CD19 chimeric antigen receptor,” J. Immunotherapy (2009) 32(7): 689-702. [cited by applicant]
Kochenderfer et al., “Adoptive transfer of syngeneic T cells transduced with a chimeric antigen receptor that recognizes murine CD19 can eradicate lymphoma and normal B cells”, Blood (2010) 116(19):3875-3886. [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):2709-2720. [cited by applicant]
Kohanski, R.A., Lane, M.D. “Monovalent avidin affinity columns” Methods Enzymol. 1990;184:194-200. [cited by applicant]
Komatsu et al., “Long-Term Survival of Patients with IgA Nephropathy After Dialysis Therapy,” Kidney Blood Press Res (2013) 37:649-656. [cited by applicant]
Koste et al., “T-cell receptor transfer into human T cells with ecotropic retroviral vectors,” Gene Therapy (2014) 21: 533-538. [cited by applicant]
Kranick et al., Aphasia as a complication of CD19-targeted chimeric antigen receptor immunotherapy (S52.006). Neurology. (2014) 82 Suppl 10:S52.006. [cited by applicant]
Kroot et al., “No increased mortality in patients with rheumatoid arthritis: up to 10 years of follow up from disease onset,” Ann Rheum Dis (2000) 59(12):954-958. [cited by applicant]
Krug et al., “A GMP-compliant protocol to expand and transfect cancer patient T cells with mRNA encoding a tumor-specific chimeric antigen receptor,” Cancer Immunol Immunother (2014) 63(10):999-1008. [cited by applicant]
Kubben et al., “Identification of differential protein interactors of lamin A and progerin,” Nucleus (2010) 1(6):513-525. [cited by applicant]
Kumar et al., “Affinity binding of cells to cryogel adsorbents with immobilized specific ligands: effect of ligand coupling and matrix architecture,” J Mol Recog (2005) 18(1):84-93. [cited by applicant]
Kumar et al., “Cell separation using cryogel-based affinity chromatography,” Nature Protocols (2010) 5(11):1737-1747. [cited by applicant]
Lada et al., “Quantitation of integrated HIV provirus by pulsed-field gel electrophoresis and droplet digital PCR,” J Clin Microbiol (2018) 56(12):e01158. [cited by applicant]
Lardo et al., “Contrast-enhanced multidetector computed tomography viability imaging after myocardial infarction: characterization of myocyte death, microvascular obstruction, and chronic scar,” Circulation (2006) 113(3… [cited by applicant]
Larvor et al., “Measurement of the dissociation rate constant of antigen/antibody complexes in solution by enzyme-linked immunosorbent assay,” J Immuno Methods (1994) 170(2):167-175. [cited by applicant]
Lee et al., “Current concepts in the diagnosis and management of cytokine release syndrome,” Blood. (2014) 124(2):188-95. [cited by applicant]
Levey et al., “A New Equation to Estimate Glomerular Filtration Rate,” Ann Intern Med (2009) 150(9):604-612. [cited by applicant]
Levin et al., “Optimizing the affinity and specificity of proteins with molecular display,” Mol BioSyst (2006) 2:49-57. [cited by applicant]
Levine et al., “Global manufacturing of CAR T cell therapy” Mol. Ther. Methods & Clin. Dev. (Dec. 2016) 4: 92-101. [cited by applicant]
Li et al., “Comparison of anti-CD3 and anti-CD28-coated beads with soluble anti-CD3 for expanding human T cells: Differing impact on CD8 T cell phenotype and responsiveness to restimulation,” J Transl Med. (2010) 8: 104. [cited by applicant]
Li et al., “Comparison of inlet geomery in microfluidic cell affinity chromatography,” Analytical chemistry (2011) 83(3):774-781. [cited by applicant]
Li et al., “Directed evolution of human T-cell receptors with picomolar affinities by phage display,” Nat Biotechnol. (2005) 23:349-354. [cited by applicant]
Li et al., “Negative enrichment of target cells by microfluidic affinity chromatography,” Analytical Chemistry (2011) 83(20):7863-7869. [cited by applicant]
Li et al., “Multiparameter cell affinity chromatography: Separation and analysis in a single microfluidic channel,” Anal Chem (20+A40312) 84(19):8140-8148. [cited by applicant]
Li et al. Identification of the earliest B lineage stage in mouse bone marrow, Immunity (1996) 5(6):527-535. [cited by applicant]
Li et al., “The regulated expression of B lineage associated genes during B ell differentiation in bone marrow and fetal liver,” J Exp Med (1993) 178(3):951-960. [cited by applicant]
Li et al., “Murine leukemia induced by retroviral gene marking,” Science (2002) 296(5567):497. [cited by applicant]
Life Technologies Corporation (2013) OpTmizer™ CTS™ T-cell Expansion SFM Technical information; pp. 1-2 (Year: 2013). [cited by applicant]
Ling et al., “B-cell and plasma cell antigens: new and previously defined clusters,” Leucocyte typing III. (1987) 302-355. [cited by applicant]
Liu et al., “Bayesian Optimal Interval Designs for Phase I Clinical Trials,” Journal of the Royal Statistical Society: Series C (2015), vol. 64, p. 507-523. [cited by applicant]
Lu et al., “A Rapid Cell Expansion Process for Production of Engineered Autologous CAR-T Cell Therapies,” Human Gene Therapy Methods (Dec. 2016) 27(6):209-218. [cited by applicant]
Lupton et al., “Dominant positive and negative selection using a hygromycin phosphotransferase-thymidine kinase fusion gene,” Mol. and Cell Biol. (1991) 11:6: 3374-3378. [cited by applicant]
Mackensen et al., “Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus,” Nat Med (2022) 28(10):2124-2132 and Supplementary Materials. [cited by applicant]
Mak et al., “Glutathione Primes T Cell Metabolism for Inflammation,” Immunity (Apr. 2017) 46(4):675-689. [cited by applicant]
Mak et al., “Glutathione Primes T Cell Metabolism for Inflammation,” Immunity (Apr. 2017) 46(6):1089-1090. [cited by applicant]
Maldonado et al., “Decreased effector memory CD45RA+ CD62L− CD8+ T cells and increased central memory CD45RA− CD62L+ CD8+ T cells in peripheral blood of rheumatoid arthritis patients,” Arthritis Res Ther. (2003) 5(2): R… [cited by applicant]
Manuri et al., “piggyBac transposon/transposase system to generate CD19-specific T cells for the treatment of B-lineage malignancies,” Hum Gene Ther (2010) 21(4): 427-437. [cited by applicant]
Marenghi et al., “The role of perfusion in maintaining high density T-cell cultures,” GE (Apr. 2014):1-2. [cited by applicant]
Marmont et al., “Autologous marrow stem cell transplantation for severe systemic lupus erythematosus of long duration,” Lupus (1997) 6:545-548. [cited by applicant]
Marmont et al., “Coincidental autoimmune disease in patients transplanted for conventional indications,” Best Practice & Research Clinical Haematology (2004) 17(2):223-232. [cited by applicant]
Marthandan et al., “An investigation of the effects of the antioxidants, ebselen or N-acetyl cysteine on human peripheral blood mononuclear cells and T cells,” Immun Ageing. (Feb. 2013) 10(1):7, 16 pages. [cited by applicant]
Maude et al., “Chimeric Antigen Receptor T Cells for Sustained Remissions in Leukemia,” N Engl J Med. (2014) 371(16):1507-1517. [cited by applicant]
McGarrity et al., “Patient monitoring and follow-up in lentiviral clinical trials,” J Gene Medicine (2013) 15: 78-82. [cited by applicant]
Medeiros-Silva et al., “CD4 and CD8 T cells participate in the immune memory response against Vaccinia virus after a previous natural infection,” Results in Immunology (2013) 3:104-13. [cited by applicant]
Medvec et al., “Improved Expansion and In Vivo Function of Patient T Cells by a Serum-free Medium,” Mol Ther Methods Clin Dev (Nov. 2017) 8:65-74. [cited by applicant]
Mei et al., “Rationale of anti-CD19 immunotherapy: an option to target autoreactive plasma cells in autoimmunity,” Arthritis Res Ther. (2012) 14 Suppl 5(Suppl 5):S1. [cited by applicant]
Menon et al., “Balanced synaptic impact via distance-dependent synapse distribution and complementary expression of AMPARs and NMDARs in hippocampal dendrites,” Neuron (2013) 80(6):1451-1463. [cited by applicant]
Menon et al., “Characterising aggressive multiple sclerosis,” Journal of Neurology, Neurosurgery & Psychiatry. (2013) 84(11):1192-8. [cited by applicant]
Merrill et al., “Efficacy and Safety of Rituximab in Moderately-to-Severely Active Systemic Lupus Erythematosus:” Arthritis Rheum (2010) 62(1):222-233. [cited by applicant]
Miller et al., “Improved retroviral vectors for gene transfer and expression,” BioTechniques (1989) 7:980-990. [cited by applicant]
Miller et al., “Retrovirus packaging cells,” Human Gene Therapy (1990) 1:5-14. [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):1453-64. [cited by applicant]
Miltenyi et al., “High Gradient Magnetic Cell Seperation With MACs”, Cytometry (1990) 11(11):231-238. [cited by applicant]
Modlich et al., “Leukemias following retroviral transfer of multidrug resistance 1 (MDR1) are driven by ombinatorial insertional mutagenesis,” Blood (2005) 105(11): 4235-4246. [cited by applicant]
Moeller et al., “Adoptive transfer of gene-engineered CD4+ helper T cells induces potent primary and secondary tumor rejection,” Blood (2005) 106(9):2995-3003. [cited by applicant]
Mohammad et al., “Incidence and survival rates in Wegener's granulomatosis, microscopic polyangiitis, Churg-Strauss syndrome and polyarteritis nodosa,” Rheumatology (Oxford) (2009) 48(12):1560-1565. [cited by applicant]
Mougiakakos et al., “CD19-Targeted CAR T Cells in Refractory Systemic Lupus Erythematosus,” N Engl J Med (2021) 385(6):567-569 and Supplementary Appendix. [cited by applicant]
Muhonen, et al., “Decreasing CD4/CD8 ratio during prolonged four-drug chemotherapy plus interferon treatment for metastatic melanoma,” J Immunother Emphasis Tumor Immunol. (1994) 15(1): 67-73. [cited by applicant]
Mullen et al., “Transfer of the bacterial gene for cytosine deaminase to mammalian cells confers lethal sensitivity to 5-fluorocytosine: a negative selection system,” Proc. Natl. Acad. Sci. USA (1992) 89:33. [cited by applicant]
Müller et al., “CD19-targeted CAR T cells in refractory antisynthetase syndrome,” The Lancet (Mar. 11, 2023) 401(10379):815-818. [cited by applicant]
Nadler et al., “B4, a human B lymphocyte-associated antigen expressed on normal, mitogen-activated, and malignant B lymphocytes,” J Immunol. (1983) 131(1):244-50. [cited by applicant]
Nagy et al., “Stability of cytotoxic luteinizing hormone-releasing hormone conjugate (AN-152) containing doxorubicin 14-O-hemiglutarate in mouse and human serum in vitro: Implications for the desig+A333n of preclinical … [cited by applicant]
Nascimbeni et al., “Peripheral CD4+CD8+ T cells are differentiated effector memory cells with antiviral functions,” Blood (2004) 104(2):478-86. [cited by applicant]
Navarra et al., “Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: a randomised, placebo-controlled, phase 3 trial,” Lancet (2011) 377(9767) p. 721-731. [cited by applicant]
Navarro et al., “Estrogen Stimulation Differentially Impacts Human Male and Female Antigen-specific T cell Anti-Tumor Function and Polyfunctionality,” Gender and the Genome (Dec. 2017) 1(4); 167-179. [cited by applicant]
Neeson et al., “Ex vivo culture of chimeric antigen receptor T cells generates functional CD8+ T cells with effector and central memory-like phenotype,” Gene Therapy (2010) 17(9):1105-1116. [cited by applicant]
Neller et al., “Tracking the repertoire of human adult and neonatal T cells during ex vivo amplification,” Br J Haematol. (2012) 159(3):370-373. [cited by applicant]
Nickerson et al., “TLR9 Regulates TLR7- and MyD88-Dependent Autoantibody Production and Disease in a Murine Model of Lupus,” J Immunol (2010) 184(4):1840-1848. [cited by applicant]
Nunez et al., “Cytokine and reactivity profiles in SLE patients following anti-CD19 CART therapy,” Mol Ther Methods Clin Dev (Dec. 2023) 31:101104, 6 pages. [cited by applicant]
Oddis et al., “Rituximab in the Treatment of Refractory Adult and Juvenile Dermatomyositis and Adult Polymyositis: A Randomized, Placebo-phase Trial,” Arthritis & Rheumatism, vol. 65(2), p. 314-324. [cited by applicant]
Okamoto et al., “A promising vector for TCR gene therapy: differential effect of siRNA, 2A peptide, and disulfide bond on the introduced TCR expression,” Mol Ther Nucl Acids (2012) 1(12):1-11. [cited by applicant]
Okern et al., “CTS™ immune cell SR for serum free culture and expansion of human T cells,” Journal for Immuno Therapy of Cancer (2015) 3(suppl 2): P1. [cited by applicant]
Okon et al., “Cutaneous Lupus Erythematosus: Diagnosis and treatment,” Best Pract Res Clin Rheumatol (2013) 27(3):391-404. [cited by applicant]
Padlan et al., “X-ray crystallography of antibodies,” Adv Prot Chem (1996) 49:57-133. [cited by applicant]
Padmanabhan et al., “Purification of transiently transfected cells by magnetic-affinity cell sorting,” J Immunogenetics (1989) 16(2):91-102. [cited by applicant]
Park et al., “KYV-101, a Fully Human Anti-CD19 CAR T Cell Therapy, Demonstrates CAR-Mediated and CD19-Dependent Activity Against Autologous B Cells from Patients with Autoimmune Disease,” American College of Rheumatolog… [cited by applicant]
Park et al., “Treating cancer with genetically engineered T cells,” Trends Biotechnol. (2011) 29(11): 550-557. [cited by applicant]
Parkhurst et al., “Characterization of genetically modified T-cell receptors that recognize the CEA:691-699 peptide in the context of HLA-A2.1 on human colorectal cancer cells,” Clin Cancer Res. (2009) 15:169-180. [cited by applicant]
Pecher et al., “CD19-Targeting CAR T Cells for Myositis and Interstitial Lung Disease Associated With Antisynthetase Syndrome,” JAMA (Jun. 2023) 329(24):2154-2162. [cited by applicant]
Pezzutto et al., “CD19 monoclonal antibody HD37 inhibits anti-immunoglobulin-induced B cell activation and proliferation,” J Immunol. (1987) 138(9):2793-9. [cited by applicant]
Pillemer et al., “Sjögrens Syndrome,” Encyclopedia of Gastroenterology (2004) p. 384-389. [cited by applicant]
Pinthus et al., “Adoptive immunotherapy of prostate cancer bone lesions using redirected effector lymphocytes,” J Clin Invest (2004) 114(12):1774-1781. [cited by applicant]
Plieva et al., “Characterization of supermacroporous monolithic polyacrylamide based matrices designed for chromatography of bioparticles,” Journal of Chromatography (2004) 807(1):129-137. [cited by applicant]
Poltorak et al., “Expamers: a new technology to control T cell activation,” Scientific Reports (Oct. 2020) 10(1):17832, 15 pages. [cited by applicant]
Porter et al., “A phase 1 trial of donor lymphocyte infusions expanded and activated ex vivo via CD3/CD28 costimulation,” Blood. (2006) 107(4): 1325-1331. [cited by applicant]
Porter et al., “Chimeric Antigen Receptor-Modified T Cells in Chronic Lymphoid Leukemia,” N Engl J Med (2011) 365(8):725-733. [cited by applicant]
Prevoo et al., “Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis,” Arthritis Rheum. (1995) 38(… [cited by applicant]
Cited By (1)
US 12,516,099