Granted Patent
B2
US 12,186,372 · App. 18/176,196 · Granted Jan 7, 2025
IL-15-based molecules and methods of treating a neoplasia
Inventors:
Bai Liu (Culver City, CA); Peter Rhode (Culver City, CA); Wenxin Xu (Culver City, CA); Hing C. Wong (Culver City, CA)
Assignee:
Altor Bioscience, LLC
A61K38/2086A61K38/1793A61K39/39558A61K47/6425A61P35/00A61K39/04C07K14/35C07K14/5443C07K14/7155C07K16/2818C07K16/2827C07K16/2887C07K16/2896C07K16/32C07K2317/732C07K2319/30C07K2319/32
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Abstract
The invention features combination therapies using an IL-15-based superagonist complex and an antibody to effectively treat subjects with cancer and infectious diseases.
Claims (21)
1. A method for treating non-small cell lung carcinoma in a human subject, wherein the subject has been previously treated with an anti-PD-1 or anti-PD-L1 antibody and subsequently experienced disease progression, the method comprising: administering to said subject a pharmaceutical composition comprising an effective amount of an anti-PD-1 or anti-PD-L1 immune checkpoint inhibitor antibody and an effective amount of an IL-15:IL-15RαSu complex, thereby treating the carcinoma.
2. The method of claim 1 , wherein IL-15:IL-15RαSu complex comprises a stabilized IL-15RαSu fusion protein.
3. The method of claim 2 , wherein the stabilized IL-15RαSu fusion protein comprises an immunoglobulin Fc domain.
4. The method of claim 1 , wherein the IL-15:IL-15RαSu complex comprises wild type IL-15.
5. The method of claim 3 , wherein the stabilized IL-15RαSuFc fusion protein comprises the amino acid sequence of SEQ ID NO: 6.
6. The method of claim 1 , wherein the effective amount of said IL-15:IL-15RαSu complex is administered daily.
7. The method of claim 1 wherein the effective amount of said IL-15:IL-15RαSu complex is between 0.1 μg/kg and 100 mg/kg.
8. The method of claim 1 , wherein the effective amount of said IL-15:IL-15RαSu complex is administered once or twice per week.
9. The method of claim 7 , wherein the effective amount of said IL-15:IL-15RαSu complex is between 0.1 μg/kg and 1 mg/kg.
10. The method of claim 1 , wherein the IL-15:IL-15RαSu complex is administered systemically, intravenously, subcutaneously, intramuscularly, intravesically, or by instillation.
11. The method of claim 1 , wherein antibody-dependent cell-mediated cytotoxicity (ADCC) or antibody dependent cellular phagocytosis (ADCP) mediated by said antibody against tumor cells in said subject is induced following said administration.
12. The method of claim 1 , wherein said antibody and said IL-15:IL-15αSu complex increases levels of blood NK cell, T cell, neutrophil or monocyte counts or activity.
13. The method of claim 1 , wherein said antibody and said IL-15:IL-15RαSu complex stimulate CD4+ or CD8+ T cells to kill tumor cells.
14. The method of claim 1 , wherein said antibody and said IL-15:IL-15αSu complex stimulate NK cells to kill tumor cells.
15. The method of claim 1 , wherein said antibody and said IL-15:IL-15RαSu complex stimulate neutrophils or monocytic cells to kill tumor cells.
16. The method of claim 1 , wherein said administration results in a decrease in the number of tumor cells.
17. The method of claim 1 , wherein said administration results in a decrease in disease progression of the carcinoma.
18. The method of claim 1 , wherein said administration results in prolonged survival of said subject compared to an untreated subject.
19. The method of claim 1 , wherein said antibody and said IL-15:IL-15RαSu complex increase blood cytokine levels.
20. The method of claim 19 , wherein said cytokine comprises IFN-γ or IL-6.
21. The method of claim 1 , wherein the antibody and pharmaceutical composition are administered in combination with surgery, radiation therapy, chemotherapy, protein-based therapy and/or biological therapy.
Assignments (3)
SECURITY INTEREST
Recorded Jan 2, 2024
From: IMMUNITYBIO, INC.; NANTCELL, INC.; RECEPTOME, INC.; VBC HOLDINGS LLC; ALTOR BIOSCIENCE, LLC; ETUBICS CORPORATION; IGDRASOL, INC.
To: INFINITY SA LLC, AS PURCHASER AGENT
Reel/Frame 066179/0074 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Apr 12, 2023
From: LIU, BAI; RHODE, PETER; XU, WENXIN; WONG, HING C.
To: ALTOR BIOSCIENCE CORPORATION
Reel/Frame 063303/0352 →
MERGER
Recorded Apr 12, 2023
From: ALTOR BIOSCIENCE CORPORATION
To: ALTOR BIOSCIENCE, LLC
Reel/Frame 063303/0489 →
Continuity (8)
Provisional Application
62018899
· Jun 30, 2014
References Cited (400)
US 5116964A
· Capon et al.
· 1992
[cited by applicant]
US 5288931A
· Chang et al.
· 1994
[cited by applicant]
US 5541087A
· Lo et al.
· 1996
[cited by applicant]
US 5620939A
· Halasa et al.
· 1997
[cited by applicant]
US 6344192B1
· Grooten et al.
· 2002
[cited by applicant]
US 7112660B1
· Domingues et al.
· 2006
[cited by applicant]
US 8124084B2
· Lefrancois et al.
· 2012
[cited by applicant]
US 8163879B2
· Wong et al.
· 2012
[cited by applicant]
US 8492118B2
· Wong et al.
· 2013
[cited by applicant]
US 8507222B2
· Wong et al.
· 2013
[cited by applicant]
US 8940288B2
· Lefrancois et al.
· 2015
[cited by applicant]
US 8940289B2
· Wong et al.
· 2015
[cited by applicant]
US 9255141B2
· Wong et al.
· 2016
[cited by applicant]
US 9328159B2
· Wong et al.
· 2016
[cited by applicant]
US 9365630B2
· Lefrancois et al.
· 2016
[cited by applicant]
US 9428573B2
· Wong et al.
· 2016
[cited by applicant]
US 9464127B2
· Wong et al.
· 2016
[cited by applicant]
US 9593152B2
· Wong et al.
· 2017
[cited by applicant]
US 9925247B2
· Klu et al.
· 2018
[cited by applicant]
US 20030045474A1
· Sailer et al.
· 2003
[cited by applicant]
US 20030144474A1
· Weidanz et al.
· 2003
[cited by applicant]
US 20030180888A1
· Fraser
· 2003
[cited by applicant]
US 20040156826A1
· Dangond et al.
· 2004
[cited by applicant]
US 20040242025A1
· Angerpointner et al.
· 2004
[cited by applicant]
US 20040253587A1
· Grabstein et al.
· 2004
[cited by applicant]
US 20060263857A1
· LeFrancois et al.
· 2006
[cited by applicant]
US 20090010966A1
· Davis et al.
· 2009
[cited by applicant]
US 20090117618A1
· Hermann et al.
· 2009
[cited by applicant]
US 20090238791A1
· Jacques
· 2009
[cited by examiner]
US 20110081311A1
· Pavlakis et al.
· 2011
[cited by applicant]
US 20130121960A1
· Sadelain et al.
· 2013
[cited by applicant]
US 20140099254A1
· Chang et al.
· 2014
[cited by applicant]
US 20140154743A1
· Levy et al.
· 2014
[cited by applicant]
US 20150023938A1
· Yee
· 2015
[cited by applicant]
US 20150152188A1
· Morisseau et al.
· 2015
[cited by applicant]
US 20170088597A1
· Wong et al.
· 2017
[cited by applicant]
US 20180200366A1
· Wong et al.
· 2018
[cited by applicant]
AU 2008253720
· 2014
[cited by applicant]
AU 2013273643
· 2016
[cited by applicant]
AU 2011305476
· 2016
[cited by applicant]
AU 2016326575
· 2018
[cited by applicant]
AU 2017201056
· 2018
[cited by applicant]
AU 2017345791
· 2019
[cited by applicant]
AU 2015284248
· 2020
[cited by applicant]
BR 112019007920
· 2019
[cited by applicant]
CA 2811734
· 2012
[cited by applicant]
CA 2953816
· 2016
[cited by applicant]
CA 2999294
· 2017
[cited by applicant]
CA 3041310
· 2018
[cited by applicant]
CA 2690825
· 2019
[cited by applicant]
CN 1441675
· 2003
[cited by applicant]
CN 1478098
· 2004
[cited by applicant]
CN 1493687
· 2004
[cited by applicant]
CN 1760209
· 2006
[cited by applicant]
CN 1780856
· 2006
[cited by applicant]
CN 1942481
· 2007
[cited by applicant]
CN 101360827
· 2009
[cited by applicant]
CN 101484472
· 2009
[cited by applicant]
CN 101743249A
· 2010
[cited by applicant]
CN 104672325
· 2015
[cited by applicant]
CN 105017429
· 2015
[cited by applicant]
CN 106659775
· 2017
[cited by applicant]
CN 101743249B
· 2017
[cited by applicant]
CN 103370339
· 2017
[cited by applicant]
CN 104109200
· 2018
[cited by applicant]
CN 107880136
· 2018
[cited by applicant]
CN 108463239
· 2018
[cited by applicant]
CN 108948177
· 2018
[cited by applicant]
CN 110799528
· 2020
[cited by applicant]
EP 0971728
· 2000
[cited by applicant]
EP 1777294
· 2007
[cited by applicant]
EP 1934353
· 2008
[cited by applicant]
EP 2388266A2
· 2011
[cited by applicant]
EP 2537933
· 2012
[cited by applicant]
EP 2388266B1
· 2014
[cited by applicant]
EP 2160401
· 2014
[cited by applicant]
EP 2619229
· 2016
[cited by applicant]
EP 3160498
· 2017
[cited by applicant]
EP 2769984
· 2017
[cited by applicant]
EP 2918607
· 2017
[cited by applicant]
EP 3305805
· 2018
[cited by applicant]
EP 3327040
· 2018
[cited by applicant]
EP 3352779
· 2018
[cited by applicant]
EP 3529263
· 2019
[cited by applicant]
EP 3673915
· 2020
[cited by applicant]
EP 3912637
· 2021
[cited by applicant]
IN 201917020025
· 2019
[cited by applicant]
JP H0687898
· 1994
[cited by applicant]
JP H09512165
· 1997
[cited by applicant]
JP H11500908
· 1999
[cited by applicant]
JP 2001502521
· 2001
[cited by applicant]
JP 2003026599
· 2003
[cited by applicant]
JP 2008545397
· 2008
[cited by applicant]
JP 2009512433
· 2009
[cited by applicant]
JP 2010527919
· 2010
[cited by applicant]
JP 6251570
· 2011
[cited by applicant]
JP 2013541335
· 2013
[cited by applicant]
JP 5501222
· 2014
[cited by applicant]
JP 2014524737
· 2014
[cited by applicant]
JP 5841623
· 2015
[cited by applicant]
JP 6152156
· 2017
[cited by applicant]
JP 2017521410
· 2017
[cited by applicant]
JP 2018046831
· 2018
[cited by applicant]
JP 6408039
· 2018
[cited by applicant]
JP 2018174697
· 2018
[cited by applicant]
JP 2018532729
· 2018
[cited by applicant]
JP 2019033754
· 2019
[cited by applicant]
JP 2019533449
· 2019
[cited by applicant]
KR 1020070000252
· 2007
[cited by applicant]
KR 1020070002052
· 2007
[cited by applicant]
KR 1020140020228
· 2014
[cited by applicant]
KR 1020170047221
· 2017
[cited by applicant]
KR 20180125435
· 2018
[cited by applicant]
KR 20190091264
· 2019
[cited by applicant]
KR 102070098
· 2020
[cited by applicant]
MX 2017000116
· 2017
[cited by applicant]
MX 2019004681
· 2019
[cited by applicant]
WO WO9404689
· 1994
[cited by applicant]
WO WO9429350
· 1994
[cited by applicant]
WO WO9527722
· 1995
[cited by applicant]
WO WO9626274
· 1996
[cited by applicant]
WO WO9632478
· 1996
[cited by applicant]
WO WO9734631
· 1997
[cited by applicant]
WO WO9741232
· 1997
[cited by applicant]
WO WO9836768
· 1998
[cited by applicant]
WO WO0156387
· 2001
[cited by applicant]
WO WO0187330
· 2001
[cited by applicant]
WO WO03080672
· 2003
[cited by applicant]
WO WO2005046449
· 2005
[cited by applicant]
WO WO2005085282
· 2005
[cited by applicant]
WO WO2006063974
· 2006
[cited by applicant]
WO WO2007001677
· 2007
[cited by applicant]
WO WO2007046006
· 2007
[cited by applicant]
WO WO2008143794
· 2008
[cited by applicant]
WO WO2009002562
· 2008
[cited by applicant]
WO WO2009117117
· 2009
[cited by applicant]
WO WO2012040323
· 2012
[cited by applicant]
WO WO2012175222
· 2012
[cited by applicant]
WO WO2013076183
· 2013
[cited by applicant]
WO WO2014028776
· 2014
[cited by applicant]
WO WO2014066527
· 2014
[cited by applicant]
WO WO2015109124
· 2015
[cited by applicant]
WO WO2016004060
· 2016
[cited by applicant]
WO WO2017053649
· 2017
[cited by applicant]
WO WO2017205726
· 2017
[cited by applicant]
WO WO2018075989
· 2018
[cited by applicant]
US 11,197,929 B2, 12/2021, Wong et al. (withdrawn)
[cited by applicant]
Byers, T. , What can randomized controlled trials tell us about nutrition and cancer prevention, CA Canc. J. Clin, 49(6):3530361, 1999.
[cited by examiner]
Vincent et al., Highly potent anti-CD20-RLI immunocytokine targeting established human B lymphoma in SCID mouse, mAbs, 6(4):1026-1037, DOI: 10.4161/mabs.28699, Apr. 2014.
[cited by examiner]
Shitara et al., Efficacy and Safety of Pembrolizumab or Pembrolizumab Plus Chemotherapy vs Chemotherapy Alone for Patients With First-line, Advanced Gastric Cancer The Keynote-062 Phase 3 Randomized Clinical Trial, JAMA…
[cited by examiner]
Reck et al., Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancre, New England J. Med. 375(19):1823-1833, Nov. 10, 2016.
[cited by examiner]
ClinicalTrials.gov,, NCT03228667, QUILT-3.055: A Study of Combination Immunotherapies in Patients Who Have Previously Received Treatment With Immune Checkpoint Inhibitors, Retrieved Feb. 28, 2024 online from <URL:https:…
[cited by examiner]
Merk Company Statement, Merck Announces Generic Name for MK-3475, Merck's Investigational anti-PD-1 Antibody: Pembrolizumab, Retreived Feb. 28, 2024 online from <URL:https://www.merck.com/news/merck-announces-generic-na…
[cited by examiner]
Wu, J., IL-15 Agonists: The Cancer Cure Cytokine, J. Mol. Genet .Med. 7: 85, 5 pages, Oct. 28, 2013.
[cited by examiner]
McKinley et al., Early discontinuation of immune checkpoint inhibitor therapy prior to disease progression in patients with metastatic non-small cell lung cancer: a survival analysis, Frontiers Oncol., vol. 14, doi.org/…
[cited by examiner]
Schoenfeld et al., Acquired Resistance to Immune Checkpoint Inhibitors, Canc. Cell, 37(4):443-455, Apr. 13, 2020.
[cited by examiner]
Davies, M., New modalities of cancer treatment for NSCLC: focus on immunotherapy, Canc. Management Res. 6:63-74, Feb. 3, 2014.
[cited by examiner]
U.S. Appl. No. 18/045,572, filed Oct. 11, 2022, Liu et al.
[cited by applicant]
U.S. Appl. No. 18/063,871, filed Dec. 9, 2022, Liu et al.
[cited by applicant]
U.S. Appl. No. 18/175,112, filed Feb. 27, 2023, Liu et al.
[cited by applicant]
“History of Changes for Study: NCT02138734, A Study of Intravesical Bacillus Calmette-Guerin (BCG) in Combination With ALT-803 in Patients With BCG-naïve Non-Muscle Invasive Bladder Cancer” Clinical Trials, (first poste…
[cited by applicant]
Gene Characterization Kits (1988), Strategene Catalog, 2 pages.
[cited by applicant]
“N-803 Plus BCG Elicits 72% CR in BCG-Unresponsive, High-Grade Non-Muscle Invasive Bladder Cancer” Dec. 2020, Onclive. Accessed Apr. 15, 2021, 15 pages.
[cited by applicant]
Press Release, Feb. 16, 2021, ImmunityBio, Inc.: ASCO Genitourinary Cancer symposium 2021 presentation: Phase 11/111 clinical results of IL-15RaFc superagonist N-803 with BCG in BCG-unresponsive non-muscle invasive blad…
[cited by applicant]
Alam et al. (Feb. 1999) “Qualitative and Quantitative Differences in T Cell Receptor Binding of Agonist and Antagonist Ligands”, Immunity, 10(2):227-237.
[cited by applicant]
Alaoui-Ismaili et al., “Design of second generation therapeutic recombinant bone morphogenetic proteins,” Cytokine Growth Factor Reviews, 2009, vol. 20(5-6), pp. 501-507).
[cited by applicant]
Alpdogan et al. (Jan. 2005) “IL-7 and IL-15: Therapeutic Cytokines for Immunodeficiency”, Trends in Immunology, 25-26(1):56-64.
[cited by applicant]
Anderson et al. (1995) “Functional Characterization of the Human Interleukin-15 Receptor a Chain and Close Linkage of IL 15RA and IL2RA Genes”, The Journal of Biological Chemistry, 270(50):29862-29869.
[cited by applicant]
Anonymous (May 15, 2014) “A Study of Intravesical BCG in Combination With ALT-803 in Patients with Non-Muscle Invasive Bladder Cancer”, ClinicalTrials.gov, NTC02138734, 9 Pages.
[cited by applicant]
Arcaro et al. (Nov. 19, 2001) “CD8˜ Endows CD8 with Efficient Coreceptor Function by Coupling T Cell Receptor/CD3 to Raft-associated CD8/p56lck Complexes”, Journal of Experimental Medicine, 194(10):1485-1495.
[cited by applicant]
Baeuerle et al. (Feb. 2009) “BITE: Teaching Antibodies to Engage T-Cells for Cancer Therapy”, Current Opinion in Molecular Therapeutics, 11(1):22-30.
[cited by applicant]
Bailey et al. (2013) “New Interleukin-15 Superagonist (IL-15 SA) Significantly Enhances Graft-Versus-Tumor Activity After Allogeneic Hematopoietic Stem Cell Transplantation”, Blood, 122(21):05 pages.
[cited by applicant]
Bailey et al. (Jul. 4, 2017) “New Interleukin-15 Superagonist (IL-15SA) Significantly Enhances Graft-versus-tumor Activity”, Oncotarget, 8(27):44366-44378.
[cited by applicant]
Bazan et al. (Dec. 2012) “Phage display-A Powerful Technique for Immunotherapy”, Human Vaccines & Immunotherapeutics, 8(12):1817-1828.
[cited by applicant]
Beers et al. (1999) “The Merck Manual of Diagnosis and Therapy”, 17th Edition, 986-995.
[cited by applicant]
Belmont et al. (Oct. 2006) “Potent Antitumor Activity of a Tumor-specific Soluble TCR/IL-2 Fusion Protein”, Journal of Clinical Immunology, 121(1):29-39.
[cited by applicant]
Benton et al. (Apr. 8, 1977) “Screening λgt Recombinant Clones by Hybridization to Single Plaques in Situ”, Science, 196(4286):180-182.
[cited by applicant]
Bergamaschi et al. (Feb. 15, 2008) “Intracellular Interaction of Interleukin-15 with its Receptor Alpha during Production Leads to Mutual Stabilization and Increased Bioactivity”, Journal of Biological Chemistry, 28(7):…
[cited by applicant]
Bernard et al. (Jun. 4, 2004) “Identification of an Interleukin-15α Receptor-binding Site on Human Interleukin-15”, Journal of Biological Chemistry, 279(23):24313-24322.
[cited by applicant]
Bernier et al., “Pharmacological chaperone action on G-protein-coupled receptors,” Current Opinion in Pharmacology, 2004, vol. 4, pp. 528-533.
[cited by applicant]
Bessard et al. (Sep. 2009) “High Antitumor Activity of RLI, An Interleukin-15 (IL-15)-IL-15 Receptor a Fusion Protein, in Metastatic Melanoma and Colorectal Cancer”, Molecular Cancer Therapeutics, 8(9):2736-2745.
[cited by applicant]
Bevan (Aug. 1997) “In Thymic Selection, Peptide Diversity Gives and Takes Away”, Immunity, 7(2): 175-178.
[cited by applicant]
Bhattacharya et al., “Impact of genetic variation on three dimensional structure and function of proteins,” PLoS ONE, 2017, vol. 12(3), pp. e0171355, 22 pages.
[cited by applicant]
Bjorkman (Apr. 18, 1997) “MHC Restriction in Three Dimensions: A View of T Cell Receptor/Ligand Interactions”, Cell, 89(2):167-170.
[cited by applicant]
Bork, Peer, “Powers and Pitfalls in Sequence Analysis: The 70% Hurdle,” Genome Research, vol. 10 (2000):398-400.
[cited by applicant]
Borras et al. (Mar. 19, 2010) “Generic Approach for the Generation of Stable Humanized Single-chain Fv Fragments from Rabbit Monoclonal Antibodies”, The Journal of Biological Chemistry, 285(12):9054-9066.
[cited by applicant]
Bouchaud et al., “The Exon-3-Encoded Domain of IL-15Rα Contributes to IL-15 High-Affinity Binding and Is Crucial for the IL-15 Antagonistic Effect of Soluble IL-15Rα”, Journal of Molecular Biology, Sep. 26, 2008, vol. 3…
[cited by applicant]
Bruhns (Apr. 16, 2009) “Specificity and Affinity of Human Fcγ Receptors and their Polymorphic Variants for human IgG Subclasses”, Blood, 113(16):3716-3725.
[cited by applicant]
Busch et al. (May 1, 2002) “Stabilization of Soluble, Low-Affinity HLA-DM/HLA-DR1 Complexes by Leucine Zippers”, Journal of Immunological Methods, 263(1-2):111-121.
[cited by applicant]
Cany et al. (Jan. 11, 2018) “Decitabine Enhances Targeting of AML Cells by CD34+ Progenitor-Derived NK Cells in NOD/SCID/IL2Rgnull Mice”, Blood, 131(2):202-214.
[cited by applicant]
Capon et al. (Feb. 9, 1989) “Designing CD4 Immunoadhesins for AIDS Therapy”, Nature, 337(6207):525-531.
[cited by applicant]
Card et al. (Nov. 11, 2003) “A Soluble Single-Chain T-Cell Receptor IL-2 Fusion Protein Retains MHC-Restricted Peptide Specificity and IL-2 Bioactivity”, Cancer Immunology, Immunotherapy, 53(4):345-357.
[cited by applicant]
Chae et al. (1996) “Mutant IL-15 Protein Exerting Antagonistic Effects on IL-15 Triggered Cell Proliferation”, Journal of the American Society of Nephrology, 7(9):1654.
[cited by applicant]
Chamow et al. (Feb. 1996) “Immunoadhesins: Principles and Applications”, Trends Biotechnology, 14:52-60.
[cited by applicant]
Chan et al. (May 2010) “Therapeutic Antibodies for Autoimmunity and Inflammation”, Nature Reviews Immunology, 10(5):301-316.
[cited by applicant]
Cheever (Apr. 2008) “Twelve Immunotherapy Drugs That Could Cure Cancers”, Immunological Reviews, 222(1):357-368.
[cited by applicant]
Chirifu et al. (Jul. 22, 2007) “Crystal Structure of the IL-15-IL-15Rα Complex, a Cytokine-Receptor Unit Presented in Trans”, Nature Immunology, 8:1001-1007.
[cited by applicant]
Chu et al. (Mar. 2016) “Therapeutic Effects of AL T-803, an IL-15 Superagonist, in Combination with Anti-CD20 Chimeric Antigen Receptor Modified Expanded Natural Killer Cells Against Burkitt Lymphoma (BL)”, Biology of B…
[cited by applicant]
Cole et al. (Feb. 19, 2008) “T Cell Receptor Engagement of Peptide-Major Histocompatibility Complex Class I Does Not Modify CD8 Binding”, Molecular Immunology, 45(9):2700-2709.
[cited by applicant]
Conlon et al. (Jan. 1, 2005) “Redistribution, Hyperproliferation, Activation of Natural Killer Cells and CD8 T Cells, and Cytokine Production During First-In-Human Clinical Trial of Recombinant Human Interleukin-15 in P…
[cited by applicant]
Cragg et al. (Apr. 1, 2004) “Antibody Specificity Controls in Vivo Effector Mechanisms of Anti-Cd20 Reagents”, Blood, 103(7) :2738-274 3.
[cited by applicant]
Cuesta et al. (Apr. 2009) “In Vivo Tumor Targeting and Imaging with Engineered Trivalent Antibody Fragments Containing Collagen-Derived Sequences”, Plos One, 4(4):(e5381):9 pages.
[cited by applicant]
Daniels et al. (2000) “Critical Role for Cd8 in T Cell Receptor Binding and Activation by Peptide/Major Histocompatibility Complex Multimers”, Journal of Experimental Medicine, 191(2):335-346.
[cited by applicant]
Database Genbank (Dec. 19, 1995) “Human Interleukin-15 receptor Alpha Chain Precursor (IL 15RA) mRNA, complete eds”, Genbank Accession No. U31628.1, 2 pages.
[cited by applicant]
Database Genbank (May 20, 2005) “Mus Musculus Interleukin 15 Receptor, Alpha Chain, mRNA (cDNA clone Image:4457379), complete eds”, Genbank Accession No. BC095982.1, 2 pages.
[cited by applicant]
Database Genbank (Sep. 14, 1995) “Mus Musculus Interleukin 15 (IL15) mRNA, complete eds”, Genbank Accession No. U14332.1, 2 pages.
[cited by applicant]
Database Genbank (Sep. 21, 1994) “Human Interleukin 15 (IL 15) mRNA, complete eds”, Genbank Accession No. U14407.1, 2 pages.
[cited by applicant]
Database UniProt Sequence, retrieved from EBI, Database Accession No. 097687, XP002659759 (1999), 1 page, 1999.
[cited by applicant]
Database UniProt Sequence, retrieved from EBI, Database Accession No. Q6B416, XP002659761, 1 page, 2004.
[cited by applicant]
Database UniProt Sequence, retrieved from EBI, Database Accession No. Q8SPYO, XP002659760, 1 page, 2002.
[cited by applicant]
Davis (1985) “Molecular Genetics of the T Cell-receptor Beta Chain”, Annual Review of Immunology, 3:537-560.
[cited by applicant]
Davis (1998) “Ligand Recognition by αβ T Cell Receptors”, Annual Reviews Immunology, 16:523-544.
[cited by applicant]
Davis et al. (Aug. 4, 1988) “T-cell Antigen Receptor Genes and T-cell Recognition”, Nature, 334(6181):395-402.
[cited by applicant]
Deer et al. (2004) “High-Level Expression of Proteins in Mammalian Cells Using Transcription Regulatory Sequences from the Chinese Hamster EF-1α Gene”, Cell Culture and Tissue Engineering. 20(3):880-889.
[cited by applicant]
Desbois et al. (May 23, 2016) “IL-15 Trans-Signaling with the Superagonist RLI Promotes Effector/Memory CD8+ T Cell Responses and Enhances Antitumor Activity of PD-1 Antagonists”, The Journal of Immunology, 97(1):168-17…
[cited by applicant]
Disis et al., “Avelumab (MSB0010718C; anti-PD-L1) in patients with recurrent/refractory ovarian cancer from the Javelin Solid Tumor phase Ib trial: Safety and clinical activity,” Journal of Clinical Oncology, 2016 ASCO …
[cited by applicant]
Doerks, Tobias et al., “Protein annotation: detective work for function prediction,” TIG, vol. 14, Issue 6 (1998):248-250.
[cited by applicant]
Dubois et al. (2008) “Preassociation of IL-15 with IL-15Rα-IgG1-Fc Enhances Its Activity on Proliferation of NK and CD8+/CD44high T Cells and Its Antitumor Action”, Journal of Immunology, 180(4):2099-2106.
[cited by applicant]
Dubois et al. (Sep. 17, 1999) “Natural Splicing of Exon 2 of Human Interleukin-15 Receptor α-Chain mRNA Results in a Shortened Form with a Distinct Pattern of Expression”, The Journal of Biological Chemistry, 274(38):26…
[cited by applicant]
Dudley et al. (Sep. 2003) “Adoptive-Cell-Transfer Therapy for the Treatment of Patients with Cancer”, Nature Review Cancer, 3:665-695.
[cited by applicant]
Eisen et al. (1996) “Antigen-Specific T-Cell Receptors and Their Reactions with Complexes Formed by Peptides with Major Histocompatibility Complex Proteins”, Advances in Protein Chemistry, 49:1-56.
[cited by applicant]
Ellison et al. (Jul. 10, 1982) “The Nucleotide Sequence of a Human Immunoglobulin Cyl gene”, Nucleic Acids Research, 10(13):4071-4079.
[cited by applicant]
Epardaud et al. (Apr. 15, 2008) “Interleukin-15/Interleukin-15Rα Complexes Promote Destruction of Established Tumors by Reviving Tumor-Resident CD8+ T Cells”, Cancer Research, 68(8):2972-2983.
[cited by applicant]
Fabbi et al. (2016) “Dual Roles of IL-15 in Cancer Biology”, Journal of Cytokine Biology, 1(2):103, 7 pages.
[cited by applicant]
Feldmann (May 1, 2002) “Development of Anti-TNF Therapy for Rheumatoid Arthritis”, Nature Reviews Immunology 2:364-371.
[cited by applicant]
Felices et al. (Dec. 2016) “CD16-IL 15-CD33 Trispecific Killer Engager (TriKE) Overcomes Cancer-Induced Immune Suppression and Induces Natural Killer Cell-Mediated Control of MDS and AML Via Enhanced Killing Kinetics”, …
[cited by applicant]
Felices et al. (Feb. 21, 2017) “IL-15 Super-Agonist (ALT-803) Enhances Natural Killer (NK) Cell Function Against Ovarian Cancer”, Gynecologic Onocology, 145(3): 19 pages.
[cited by applicant]
Ferrari-Lacraz et al. (Dec. 15, 2006) “CD8+ T Cells Resistant to Costimulatory Blockade Are Controlled by an Antagonist Interleukin-15/Fc Protein”, Transplantation, 82(11):14 pages.
[cited by applicant]
Ferrari-Lacraz et al. (Nov. 1, 2004) “Targeting IL-15 Receptor-Bearing Cells with an Antagonist Mutant IL-15/Fc Protein Prevents Disease Development and Progression in Murine Collagen-Induced Arthritis”, The Journal of …
[cited by applicant]
Ferrari-Lacraz et al. (Sep. 15, 2001) “An antagonist IL-15/Fc protein prevents costimulation blockade-resistant rejection”, Journal of Immunology, 167(6): 3478-3485.
[cited by applicant]
Fleer (Oct. 1992) “Engineering Yeast for High Level Expression”, Current Opinion in Biotechnology, 3(5):486-496.
[cited by applicant]
Frankel et al. (Oct. 2000) “Cell Surface Receptor-Targeted Therapy of Acute Myeloid Leukemia: A Review”, Cancer Biotherapy & Radiopharmaceuticals, 15(5) :459-47 6.
[cited by applicant]
Gakamsky et al. (Sep. 2005) “CD8 Kinetically Promotes Ligand Binding to the T-Cell Antigen Receptor”, Biophysical Journal, 89(3):2121-2133.
[cited by applicant]
Galfre, et al., (1981) “Preparation of Monoclonal Antibodies: Strategies and Procedures”, Methods in Enzymology, 73(Pt B):3-46, publication nummary, 2 pages.
[cited by applicant]
Garboczi et al. (Apr. 15, 1989) “HLA-A2-Peptide Complexes: Refolding and Crystallization of Molecules Expressed in
[cited by applicant]
Garboczi et al. (Nov. 14, 1996) “Pillars Article: Structure of the Complex Between Human T-cell Receptor, Viral Peptide and HLA-A2”, Nature, 384:134-141.
[cited by applicant]
Gerber et al. (2009) “Antibody Drug-Conjugates Targeting the Tumor Vasculature-Current and Future Developments”, mAbs, 1 (3) :24 7-253.
[cited by applicant]
Gillies et al. (May 15, 2005) “An Anti-CD20-IL-2 Immunocytokine is Highly Efficacious in A SCIO Mouse Model of Established Human B Lymphoma”, Blood, 105(10):3972-3978.
[cited by applicant]
Golay et al. (Nov. 14, 2013) “Glycoengineered CD20 Antibody Obinutuzumab Activates Neutrophils and Mediates Phagocytosis Through CD16B More Efficiently Than Rituximab”, Blood, 122(20):3482-3491.
[cited by applicant]
Gomes et al. (May 5, 2013) “IL-15 Analogue (ALT-803) Targeting T Regulatory Cells Causes Tomor Burden Reduction in an Orthotopic Non-Muscle Invasive Bladder Cancer Model,” The Journal of Urology, 189(4S):e238-e239.
[cited by applicant]
Gomes-Giacoia et al. (Jun. 4, 2014) “Intravesical ALT-803 and BCG Treatment Reduces Tumor Burden in a Carcinogen Induced Bladder Cancer Rat Model; a Role for Cytokine Production and NK Cell Expansion”, PLoS One, e96705,…
[cited by applicant]
Graham et al. (Jul. 1977) “Characteristics of a Human Cell Line Transformed by DNA from Human Adenovirus Type 5”, Journal of General Virology, 36(1):59-72.
[cited by applicant]
Grunstein et al. (Oct. 1975) “Colony Hybridization: A Method for the Isolation of Cloned DNAs That Contain a Specific Gene”, Proceedings of the National Academy of Sciences of the United States of America, 72(10):3961-3…
[cited by applicant]
Guglielmi et al. (Jul. 15, 2002) “Donor lymphocyte infusion for relapsed chronic myelogenous leuken1 ia: prognostic relevance of the initial cell dose”, Blood, 100(2):295-307.
[cited by applicant]
Guo et al. (2013) “Therapeutic Cancer Vaccines: Past, Present and Future”, Advances in Cancer Research, 119:421-475.
[cited by applicant]
Guo et al., “Protein tolerance to random amino acid change,” PNAS USA, 2004, vol. 101(25), pp. 9205-9210.
[cited by applicant]
Han et al., “IL-15:IL-15 receptor alpha superagonist complex: High-level co-expression in recombinant mammalian cells, purification and characterization”, Cytokine, Sep. 28, 2011, vol. 56(3), pp. 804-810.
[cited by applicant]
Hara et al. (Nov. 1, 1995) “Implicating a Role for Immune Recognition of Self in Tumor Rejection: Passive Immunization Against the Brown Locus Protein”, Journal of Experimental Medicine, 182(5):1609-1614.
[cited by applicant]
Hatzimichael et al. (2010) “Hematopoietic stem cell transplantation”, Stem Cells and Cloning: Advances and Applications, 3:105-117.
[cited by applicant]
Hayden-Ledbetter et al. (Apr. 2009) “CD20-Directed Small Modular Immunopharmaceutical, TRU-015, Depletes Normal and Malignant B Cells”, Clinical Cancer Research, 15(8):2739-2746.
[cited by applicant]
Hessell et al. (Sep. 6, 2007) “Fc Receptor but Not Complement Binding is Important in Antibody Protection Against HIV”, Nature, 449(7158):101-104.
[cited by applicant]
Hezareh et al. (Dec. 2001) “Effector Function Activities of a Panel of Mutants of a Broadly Neutralizing Antibody against Human Immunodeficiency Virus Type 1”, Journal of Virology, 75(24):12161-12168.
[cited by applicant]
Hogquist et al. (Jan. 1994) “T Cell Receptor Antagonist Peptides Induce Positive Selection”, Cell, 76(1): 17-27.
[cited by applicant]
Holliger et al. (Sep. 2005) “Engineered Antibody Fragments and the Rise of Single Domains”, Nature Biotechnology, 23(9):1126-1136.
[cited by applicant]
Huang, J., et al. Intravesical ALT-803 for BCG-unresponsive Bladder Cancer—A Case Report. Urology Case Reports 14 (2017) 15-17.
[cited by applicant]
Hughes et al. (Apr. 2005) “Transfer of a TCR Gene Derived from a Patient with a marked Antitumor Response Conveys Highly Active T-Cell Effector Functions”, Human Gene Therapy, 16(4):457-472.
[cited by applicant]
Jakobisiak et al., Interleukin 15 as a promising candidate for tumor immunotherapy. Cytokine & Growth Factor Reviews. 2011; 22:99-108.
[cited by applicant]
Kaspar et al. (May 15, 2007) “The antibody-mediated targeted delivery of interleukin-15 and GM-CSF to the tumor neovasculature inhibits tumor growth and metastasis Cancer Research”, American Association for Cancer Resea…
[cited by applicant]
Kern et al. (Sep. 17, 1999) “Expression, Purification, and Functional Analysis of Murine Ectodomain Fragments of CD8αα and CD8αβ Dimers”, The Journal of Biological Chemistry, 274:27237-27243.
[cited by applicant]
Khantasup et al. (Dec. 1, 2015) “Design and Generation of Humanized Single-chain Fv Derived from Mouse Hybridoma for Potential Targeting Application”, Monoclonal Antibodies in Immunodiagnosis and Immunotherapy, 34(6):40…
[cited by applicant]
Kim et al. (2012) “Humanization by CDR Grafting and Specificity-Determining Residue Grafting”, Methods in molecular biology, 907:237-245.
[cited by applicant]
Kim et al. (Feb. 18, 2016) “IL-15 superagonist/IL-15RαSushi-Fc fusion complex (IL-15SA / IL-15RαSu-Fc; ALT-803) markedly enhances specific subpopulations of NK and memory CD8+ T cells, and mediates potent anti-tumor act…
[cited by applicant]
Kim, Yon Su et al., “Targeting the IL-15 Receptor with an Antagonist IL-15 Mutant/Fcγ 2a Protein Blocks Delayed-Type Hypersensitivity,” The Journal of Immunology, vol. 160(1998):5742-5748.
[cited by applicant]
Kimmel (1987) “Identification and Characterization of Specific Clones: Strategy for Confirming the Validity of Presumptive Clones”, Methods in Enzymology, 152:507-511.
[cited by applicant]
Klebanoff et al. (Feb. 17, 2004) “IL-15 Enhances the in Vivo Antitumor Activity of Tumor-Reactive CD8+ T Cells”, Proceedings of the National Academy of Sciences of the United States of America, 101(7):1969-1974.
[cited by applicant]
Kobayashi et al. (Dec. 15, 1994) “Tyrosinase Related Protein 1 (TRP1) Functions as a DHICA Oxidase in Melanin Biosynthesis”, The EMBO Journal, 13(24):5818-5825.
[cited by applicant]
Kostelny et al. (Mar. 1, 1992) “Formation of A Bispecific Antibody by the Use of Leucine Zippers”, Journal of Immunology, 148(5):1547-1553.
[cited by applicant]
Kouzarides et al. (Aug. 17, 1989) “Leucine zippers of fos, jun and GCN4 dictate dimerization specificity and hereby control DNA binding”, Nature, 340:568-571.
[cited by applicant]
Kouzarides et al. (Dec. 15, 1988) “The role of the leucine zipper in the fos-jun Interaction”, Nature, 336:646-651.
[cited by applicant]
Kruif et al. (Mar. 29, 1996) “Leucine Zipper Dimerized Bivalent and Bispecific scFv Antibodies from a Semi-synthetic Antibody Phage Display Library”, The Journal of Biological Chemistry, 271:7630-7634.
[cited by applicant]
Kubetzko et al. (Nov. 17, 2006) “PEGylation and Multimerization of the Anti-p185HER-2 Single Chain Fv Fragment 4D5-Effects on Tumor Targeting”, The Journal of Biological Chemistry, 281 :35186-35201.
[cited by applicant]
Laugel et al. (Aug. 17, 2007) “Different T Cell Receptor Affinity Thresholds and CD8 Coreceptor Dependence 43 Govern Cytotoxic T Lymphocyte Activation and Tetramer Binding Properties”, The Journal of Biological Chemistr…
[cited by applicant]
Lawrencia et al. (May 2001) “Transfection of Urothelial Cells using Methyl-β-Cyclodextrin Solubilized Cholesterol and Dotap”, Gene Therapy, 8(10):760-768.
[cited by applicant]
Lazar et al. (Mar. 14, 2006) “Engineered Antibody Fe Variants with Enhanced Effector Function”, Proceedings of the National Academy of Sciences, 103(11):4005-4010.
[cited by applicant]
Lazar et al. (Mar. 1988) “Transforming Growth Factor α: Mutation of Aspartic Acid 47 and Leucine 48 Results in Different Biological Activities”, Molecular and Cellular Biology, 8(3):1247-1252.
[cited by applicant]
Lin et al. (Aug. 10, 1990) “Expression of T Cell Antigen Receptor Heterodimers in a Lipid-Linked Form”, Science, 249(4969) :677-679.
[cited by applicant]
Liu et al. “A Novel Fusion of ALT-803 (Interleukin (IL)-15 Superagonist) with an Antibody Demonstrates Antigen-specific Antitumor Responses,” Journal of Biological Chemistry, 2016, vol. 291(46), pp. 23869-23881. Online …
[cited by applicant]
Liu et al. (Dec. 2014) “Evaluation of a Novel CD20-Targeted IL-15 Immunotherapeutic with Potent Activity Against B Cell Lymphoma”, Journal for ImmunoTherapy of Cancer, 2(Suppl 3):1 page.
[cited by applicant]
Lu et al. (2009) “Construction and Production of an IgG-like Tetravalent Bispecific Antibody for Enhanced Therapeutic Efficacy”, Methods in Molecular Biology, 525:377-404.
[cited by applicant]
Mathios et al. (Jan. 1, 2016) “Therapeutic Administration of IL-15 Superagonist Complex AL T-803 Leads to Long-term Survival and Durable Antitumor Immune Response in a Murine Glioblastoma Model”, International Journal o…
[cited by applicant]
Matsumoto et al., Intravesical Interleukin-15 Gene Therapy in an Orthotopic Bladder Cancer Model. Human Gene Therapy. Nov. 2011; 22:1423-1432.
[cited by applicant]
Mclaughlin et al. (2015) “Adoptive T-cell therapies for refractory/ relapsed leukemia and lymphoma: current strategies and recent advances”, Therapy Advance Hematology, 6(6):295-307.
[cited by applicant]
Mohler et al. (Aug. 1, 1993) “Soluble Tumor Necrosis Factor (TNF) Receptors Are Effective Therapeutic Agents in 3 Lethal Endotoxemia and Function Simultaneously as Both TNF Carriers and TNF Antagonists”, The Journal of …
[cited by applicant]
Mortier et al. (Jan. 20, 2006) “Soluble Interleukin-15 Receptor α (IL-15Rα)-sushi as a Selective and Potent Agonist of IL-15 Action through IL-15Rβ/γ”, The Journal of Biological Chemistry, 281(3):1612-1619.
[cited by applicant]
Morton et al. (Nov. 1, 2016) “Humanized Mouse Xenograft Models: Narrowing the Tumor-Microenvironment Gap”, Cancer Research, 76(21):6153-6158.
[cited by applicant]
Moskaug et al. (Sep. 15, 1989) “Translocation of Diphtheria Toxin A—Fragment to the Cytosol. Role of The Site of Interfragment Cleavage”, Journal of Biological Chemistry, 264(26):15709-15713.
[cited by applicant]
Mosquera et al. (Apr. 1, 2005) “In Vitro And In Vivo Characterization Of A Novel Antibody-Like Single-Chain TCR Human IgG1 Fusion Protein”, Journal of Immunology, 174(7):4381-4388.
[cited by applicant]
Neveu et al. (Jul. 2006) “Impact of CD8-MHC Class I Interaction in Detection and Sorting Efficiencies of Antigen-7 Specific T Cells Using MHC Class I/peptide Multimers: Contribution of pMHC Valency”, International Immun…
[cited by applicant]
Ng et al. (2005) “Liposomal Polyene Antibiotics”, Methods in Enzymology, 391 :304-313.
[cited by applicant]
Nogawa et al. (Apr. 2005) “Intravesical Administration of Small Interfering RNA Targeting PLK-1 Successfully Prevents the Growth of Bladder Cancer”, Journal of Clinical Investigation, 115(4):978-985.
[cited by applicant]
Novellino et al. (Mar. 2005) “A Listing of Human Tumor Antigens Recognized by T Cells: Mar. 2004 Update”, Cancer Immunology, Immunotherapy, 54(3):187-207.
[cited by applicant]
Nugent et al. (May 15, 2005) “Low Binding Capacity of Murine Tetramers Mutated at Residue 227 Does Not Preclude the Ability to Efficiently Activate CD8+ T Lymphocytes”, Immunology Letters, 98(2):208-215.
[cited by applicant]
Oleksiewicz et al. (Oct. 15, 2012) “Anti-bacterial Monoclonal Antibodies: Back to the Future?”, Archives of Biochemistry and Biophysics, 526(2):124-131.
[cited by applicant]
Olsnes et al. (1982) “Chimeric Toxins”, Pharmacology and Therapeutics, 15(3):355-381.
[cited by applicant]
Orti et al. (2017) “Donor lymphocyte infusions in AML and MOS: Enhancing the grafl-versus-leuke1nia effect”, Experimental Hematology, 48:1-11.
[cited by applicant]
Ortiz-Sanchez et al. (May 2008) “Antibody-cytokine Fusion Proteins: Applications in Cancer Therapy”, Expert Opinion on Biological Therapy, 8(5):609-632.
[cited by applicant]
Otegbeye et al. (Dec. 3, 2015) “The IL-15 Super-Agonist AL T-803 Promotes Superior Activation and Cytotoxicity of Ex Vivo Expanded NK Cells Against AML”, Blood, 3090, 126(23):4 Pages.
[cited by applicant]
Ozdemir et al. “Mechanisms of Superior Anti-Tumor Cytotoxic Response of Interleukin 15-Induced Lymphokine-Activated Killer Cells,” Journal of Immunotherapy, Jan./Feb. 2005, vol. 28(1), pp. 44-52.
[cited by applicant]
Pardoll (Apr. 2012) “The Blockade of Immune Checkpoints in Cancer Immunotherapy”, Nature Reviews Cancer, 12(4):252-264.
[cited by applicant]
Parmiani et al. (Feb. 15, 2007) “Unique Human Tumor Antigens: Immunobiology and Use in Clinical Trials”, The Journal of Immunology, 178(4):1975-1979.
[cited by applicant]
Pastan et al. (1992) “Recombinant Toxins as Novel Therapeutic Agents”, Annual Review Biochemistry, 61:331-354.
[cited by applicant]
Pastan et al. (Dec. 5, 1986) “Immunotoxins”, Cell, 47:641-648.
[cited by applicant]
Penichet et al. (1997) “Antibody-IL-2 Fusion Proteins: A Novel Strategy for Immune Protection”, Human Antibodies, 8(3):106-118.
[cited by applicant]
Pettit et al. (Jan. 24, 1997) “Structure-Function Studies of Interleukin 15 Using Site-Specific Mutagenesis, Polyethylene Glycol Conjugation, and Homology Modeling”, Journal of Biological Chemistry, 272(4):2312-2318.
[cited by applicant]
Powles et al., “MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer,” Nature, Letter, Nov. 27, 2014, vol. 515(7528), 12 pages.
[cited by applicant]
Quemener, Agnes et al., “Docking of Human Interleukin-15 to its Specific Receptor alpha Chain: Correlation Between Molecular Modeling and Mutagenesis Experimental Data,” Proteins: Structure, Function and Bioinformatics,…
[cited by applicant]
Rabinowitz et al. (Feb. 20, 1996) “Kinetic Discrimination in T-cell Activation”, Proceedings of the National Academy of Sciences of the United States of America, 93(4):1401-1405.
[cited by applicant]
Ramos et al. (Apr. 10, 2015) “Current Approaches in the Treatment of Relapsed and Refractory Acute Myeloid Leukemia”, Journal of Clinical Medicine, 4:665-695.
[cited by applicant]
Richards et al. (Aug. 2008) “Optimization of Antibody Binding to FcγRIIa Enhances Macrophage Phagocytosis of Tumor Cells”, Molecular Cancer Therapeutics, 7(8):2517-2527.
[cited by applicant]
Rieker et al. (2000) “Molecular Applications of Fusions to Leucine Zippers”, Methods in Enzymology, 328:282-296.
[cited by applicant]
Rossi et al. (Oct. 29, 2009) “CD20-Targeted Tetrameric Interferon-α, A Novel and Potent Immunocytokine for the Therapy of B-Cell Lymphomas”, Blood, 114(18):3864-3871.
[cited by applicant]
Rossi et al., “Optimization of Multivalent Bispecific Antibodies and Immunocytokines with Improved in Vivo Properties,” Bioconjugate Chemistry. 2013, vol. 24, pp. 63-71.
[cited by applicant]
Roychowdhury et al. (Nov. 1, 2004) “Failed 1-15 Adoptive Immunotherapy with Tumor-Specific T Cells: Reversal with Low-Dose Interleukin 15 but not Low-Dose Interleukin 2”, Cancer Research, 64(21):8062-8067.
[cited by applicant]
Rubinstein et al. (Jun. 13, 2006) “Converting IL-15 to a Superagonist by Binding to Soluble IL-15Rα”, Proceedings of the National Academy of Sciences of the United States of America, 103(24):9166-9171.
[cited by applicant]
Rudikoff et al., “Single amino acid substitution altering antigen-binding specificity,” PNAS, Mar. 1982, vol. 79, pp. 1979-1983.
[cited by applicant]
Sauter et al. (Apr. 29, 2013) “Interleukin-15 Administration Increases Graft-Versus-Tumor Activity in Recipients of Haploidentical Hematopoietic SCT”, Bone Marrow Transplantation, 48(9):1237-1242.
[cited by applicant]
Savio, Alicia Santos, “IL-15: a relevant cytokine for lymphoid homeostasis and autoimmune diseases,” Biotecnologia Aplicada, vol. 23 (2006):87-93.
[cited by applicant]
Schmohl et al. (Jul. 2016) “Enhanced ADCC and NK Cell Activation of an Anticarcinoma Bispecific Antibody by Genetic Insertion of a Modified IL-15 Cross-linker”, TriKE Facilitates ADCC and Sustaining of NK Cells, Molecul…
[cited by applicant]
Schott et al. (Dec. 2002) “Mouse MHC Class I Tetramers That Are Unable to Bind to CD8 Reveal the Need for CD8 Engagement in Order to Activate Naive CD8 T Cells”, European Journal of Immunology, 32(12):3425-3434.
[cited by applicant]
Shen et al. (Feb. 15, 2006) “Single Variable Domain-IgG Fusion A Novel Recombinant Approach To Fe Domain-Containing Bispecific Antibodies”, The Journal of Biological Chemistry, 281:10706-10714.
[cited by applicant]
Skolnick, Jeffrey et al., “From genes to protein structure and function: novel applications of computational approaches in the genomic era,” Trends Biotechnol., vol. 18 Issue 1 (2000):34-39.
[cited by applicant]
Sliwkowski et al. (Sep. 13, 2013) “Antibody Therapeutics in Cancer”, Science, 341 (6151):1192-1198.
[cited by applicant]
Sloan et al. (Jun. 29, 1995) “Mediation by HLA-DM of Dissociation of Peptides from HLA-DR” Nature, 375:802-806.
[cited by applicant]
Sockolosky et al. (Apr. 18, 2016) “Durable Antitumor Responses to CD47 Blockade Require Adaptive Immune Stimulation”, Proceedings of the National Academy of Sciences of the United States of America, May 10, 2016, 113(19…
[cited by applicant]
Sprent et al. (Mar. 29, 2000) “T-cell proliferation in vivo and the role of cytokines”, Philosophical Transactions of the Royal Society of London, Series B, Biological Sciences, 355(1395):317-322.
[cited by applicant]
Steel, Interleukin-15 and its Receptor Augment Dendritic Cell Vaccination Against the neu Oncogene Through the Induction of Antibodies Partially Independent of CD4-help. Cancer Res. Feb. 1, 2010; 70(3): 1-19.
[cited by applicant]
Stern et al. (Feb. 7, 1992) “The Human Class II MHC Protein HLA-DR1 Assembles as Empty αβ Heterodimers in the Absence of Antigenic Peptide”, Cell, 68(3):465-477.
[cited by applicant]
Stewart et al. (Sep. 2015; e-published on May 5, 2015) “Identification and Characterization of MEDI4736, An Antagonistic Anti-PD-L 1 Monoclonal Antibody”, Cancer Immunology Research, 3(9):1052-1062.
[cited by applicant]
Stoklasek et al. (Nov. 1, 2006) “Combined IL-15/IL-15Rα Immunotherapy Maximizes IL-15 Activity in Vivo”, Journal of Immunology, 177(9):6072-6080.
[cited by applicant]
Sukumar (Nov. 4, 2015) “Modulating Immunometabolism of Tumor Specific Mouse and Human Lymphocytes to Enhance T Cell Based Therapy for Cancer”, Journal for ImmunoTherapy of Cancer, 02, 2(Suppl 3): 2 pages.
[cited by applicant]
Tai et al. (Sep. 15, 2010) “The Role of HER2 in Cancer Therapy and Targeted Drug Delivery”, Journal of Controlled Release, 146(3):264-275.
[cited by applicant]
Tamura et al., “Structural Correlates of an Anticarcinoma Antibody: Identification of Specificity-Determining Residues (SDRs) and Development of a Minimally Immunogenic Antibody Variant by Retention of SDRs Only,” The J…
[cited by applicant]
Tay et al. (Jul. 26, 2016) “TriKEs and BiKEs Join CARs on the Cancer Immunotherapy Highway”, Human Vaccines & Immunotherapeutics, 12(11):2790-2796.
[cited by applicant]
Terawaki et al. (Jul. 2007) “Specific and High-affinity Binding ofTetramerized PD-L 1 Extracellular Domain to PD-1-expressing Cells: Possible Application to Enhance T Cell Function”, International Immunology, 19(7):881-…
[cited by applicant]
Thaventhiran et al. (2012) “T Cell Co-Inhibitory Receptors: Functions and Signalling Mechanisms”, Journal of Clinical & Cellular Immunology, S12:12 pages.
[cited by applicant]
Theobald et al. (Dec. 19, 1995) “Targeting P53 as a General Tumor Antigen”, PNAS, 92(26)11993-11997.
[cited by applicant]
Thomson et al. (Aug. 1985) “Pigmentation-associated Glycoprotein of Human Melanomas and Melanocytes: Definition With a Mouse Monoclonal Antibody”, Journal of Investigative Dermatology, 85(2):169-174.
[cited by applicant]
Tietze et al. (Mar. 29, 2012) “Delineation of Antigen-Specific and Antigen-Nonspecific CD8+ Memory T-Cell Responses after Cytokine-Based Cancer Immunotherapy”, Blood, 119(13):3073-3083.
[cited by applicant]
Tokuriki et al., “Stability effects of mutations and protein evolvabilily,” Current Opinion in Structural Biology, 2009, vol. 19, pp. 596-604.
[cited by applicant]
Tomalia (1993) “StarburstCascade Dendrimers: Fundamental Building Blocks for a New Nanoscopic Chemistry Set”, Aldrichimica Acta, 26(4):89-101.
[cited by applicant]
Tonegawa (Apr. 14, 1983) “Somatic Generation of Immune Diversity”, Bioscience Reports, 8(1):3-26.
[cited by applicant]
Tough et al. (May 15, 2001) “An IFN-γ-Dependent Pathway Controls Stimulation of Memory Phenotype CD8+ T Cell Turnover in Vivo by IL-12, IL-18, and IFN-γ”, Journal of Immunology, 166(10):6007-6011.
[cited by applicant]
Traunecker et al. (Jan. 1989) “Solubilizing the T-Cell Receptor-Problems in Solution”, Immunology Today, 10(1):29-32.
[cited by applicant]
Trevisani et al. (Jun. 2002) “Ethanol Elicits and Potentiates Nociceptor Responses via the Vanilloid Receptor-1”, Nature Neuroscience, 5(6):546-551.
[cited by applicant]
Trevisani et al. (Jun. 2004) “Ethanol Causes Inflammation in the Airways by a Neurogenic and TRPV1-Dependent Mechanism”, Journal of Pharmacology and Experimental Therapeutics, 309(3): 1167-1173.
[cited by applicant]
Tyagi et al. (Jan. 2004) “Urodynamic and Immunohistochemical Evaluation of Intravesical Capsaicin Delivery using Thermosensitive Hydrogel and Liposomes”, The Journal of Urology, 171 (1):483-489.
[cited by applicant]
Ulloa-Aguirre et al., “Pharmacologic Rescue of Conformationally-Defective Proteins: Implications for the Treatment of Human Disease,” Traffic, 2004, vol. 5, pp. 821-837.
[cited by applicant]
Urlaub et al. (Jul. 1980) “Isolation of Chinese Hamster Cell Mutants Deficient in Dihydrofolate Reductase Activity”, PNAS, 77(7):4216-4220.
[cited by applicant]
Valencia et al. (Mar. 15, 2013) “In Vitro Selection of Proteins with Desired Characteristics Using mRNA-display”, Methods, 60(1):32 pages.
[cited by applicant]
Valitutti (May 11, 1995) “Serial Triggering of Many T-Cell Receptors by a Few Peptide-MHC Complexes”, Nature, 375(6527):148-151.
[cited by applicant]
Van Den Bergh et al. (2015) “Interleukin-15: New Kid on the Block for Antitumor Combination Therapy”, Cytokine and Growth Factor Reviews, 26:15-24.
[cited by applicant]
Verbist et al., Functions of IL-15 in Anti-Viral Immunity: Multiplicity and Variety. Cytokine. Sep. 2012; 59(3):467-478.
[cited by applicant]
Villinger et al. (Sep. 3, 2004) “IL-15 is Superior to IL-2 in the Generation of Long-Lived Antigen Specific Memory CD4 And CD8 T Cells in Rhesus Macaques”, Vaccine, 22(25-26):3510-3521.
[cited by applicant]
Vincent et al. (Aug. 1, 2013) “Tumor Targeting of the IL-15 Superagonist RU by an anti-GD2 Antibody Strongly Enhances Its Antitumor Potency”, International Journal of Cancer, 133(3):757-765.
[cited by applicant]
Vincent et al. (Nov. 2013) “Antitumor Activity of an Immunocytokine Composed of an Anti-GD2 Antibody and the IL-15 Superagonist RLI”, Oncolmmunology, e26441, 2(11):3 pages.
[cited by applicant]
Vincent et al. (Oct. 2011) “Development of Two IL 15 Immunocytokines Targeting Either GD2- or CD20-tumoral Bearing Cells”, Cytokine, 56(1):1 page.
[cited by applicant]
Wahl et al. (1987) “Molecular Hybridization of Immobilized Nucleic Acids: Theoretical Concepts and Practical Considerations”, Methods in Enzymology, 152:399-407.
[cited by applicant]
Waldmann et al., IL-15 Receptor, 2000, pp. 1521-1528.
[cited by applicant]
Waldmann, Thomas A., “The biology of interleukin-2 and interleukin-15: implications for cancer therapy and vaccine design,” Nature Reviews Immunology, vol. 6 Issue 8 (2006):595-601.
[cited by applicant]
Wang et al. (Aug. 15, 2009) “Structural Basis of the CD8αβ/MHC Class I Interaction: Focused Recognition Orients CD8B to a T Cell Proximal Position”, The Journal of Immunology, 183(4):2554-2564.
[cited by applicant]
Ward et al. (Nov. 2009) “
[cited by applicant]
Wei et al. (2001) “The Sushi Domain of Soluble IL-15 Receptor a Is Essential for Binding IL-15 and Inhibiting Inflammatory and Allogenic Responses In Vitro and In Vivo”, The Journal of Immunology, 167:277-282.
[cited by applicant]
Weidanz et al. (Dec. 1, 1996) “Display of Functional αβ Single-Chain T-Cell Receptor Molecules on the Surface of Bacteriophage”, Journal of Immunological Methods, 221 (1-2):59-76.
[cited by applicant]
Weidle et al. (2013) “The Emerging Role of New Protein Scaffold-based Agents for Treatment of Cancer”, Cancer Genomics and Proteomics, 10(4):155-168.
[cited by applicant]
Weiner (Sep. 2007) “Building Better Magic Bullets—Improving Unconjugated Monoclonal Antibody Therapy for Cancer”, Nature Reviews Cancer, 7:701-706.
[cited by applicant]
Wells (Sep. 18, 1990) “Additivity of Mutational Effects in Proteins”, Biochemistry, 29(37):8509-8517.
[cited by applicant]
Wen et al. (2008) “Targeting Activity of a TCR/IL-2 Fusion Protein Against Established Tumors” Cancer Immunology Immunother, 57(12):1781-1794.
[cited by applicant]
Whitlow et al. (Apr. 1991) “Single-Chain Fv Proteins and their Fusion Proteins”, Methods: A Companion to Methods in Enzymology, 2(2):97-105.
[cited by applicant]
Wong et al. (2011) “Interleukin-15: Interleukin-15 Receptor a Scaffold for Creation of Multivalent Targeted Immune Molecules”, Protein Engineering, Design & Selection, 24(4):373-383.
[cited by applicant]
Wong et al. (May 1, 2012) “Efficacy and mechanism-of-action of a novel superagonist IL-15:IL-15Rα/Fc fusion complex in murine multiple myeloma syngeneic mouse models (46.44)”, The Journal of Immunology, 188(Suppl 1):04 …
[cited by applicant]
Wong et al. (Nov. 1, 2013) “The IL-15-based superagonist ALT-803 promotes the antigen-independent conversion of memory CD8+ T cells into innate-like effector cells with antitumor activity”, Oncoimmunology, 2(11): e26442…
[cited by applicant]
Wooldridge et al. (Jul. 29, 2005) “Interaction between the CD8 Coreceptor and Major Histocompatibility Complex Class I Stabilizes T Cell Receptor-Antigen Complexes at the Cell Surface”, The Journal of Biological Chemist…
[cited by applicant]
Wu (Oct. 28, 2013) “IL-15 Agonists: The Cancer Cure Cytokine”, Journal of Molecular and Genetic Medicine, 7(4):6 pages.
[cited by applicant]
Wu, IL-15 Agonists: The Cancer Cure Cytokine. J Mol Genet Med. Feb. 28, 2014; 7(85):1-6.
[cited by applicant]
Xiao et al. “Antitumor Efficacy of Intravesical BCG, Gemcitabine, Interferon- and Interleukin-2 as Mono- or Combination-Therapy for Bladder Cancer in an Orthotopic Tumor Model,” Clinical Medicine Insights: Oncology, 201…
[cited by applicant]
Xiong et al., “Efficient inhibition of human B-cell lymphoma xenografts with an anti-CD20 + anti-CD3 bispecific diabody,” Cancer Letters, 2002, vol. 177, pp. 29-39.
[cited by applicant]
Xu et al. (May 15, 2013) “Efficacy and Mechanism-of-Action of a Novel Superagonist Interleukin-15: Interieukin-15 Receptor αSu/Fc Fusion Complex in Syngeneic Murine Models of Multiple Myeloma”, Therapeutics, Targets and…
[cited by applicant]
Xuan et al. (Apr. 8, 2010) “Targeted Delivery of Interferon-Alpha via Fusion to Anti-CD20 Results in Potent Antitumor Activity against B-Cell Lymphoma”, Blood, 115(14):2864-2871.
[cited by applicant]
Yang et al. (Nov.-Dec. 2008) “Clinical-Scale Lentiviral Vector Transduction of PBL for TCR Gene Therapy and Potential for Expression in Less Differentiated Cells”, Journal of Immunotherapy, 31 (9):830-839.
[cited by applicant]
Yu et al. (Apr. 17, 2012) “Simultaneous Inhibition ofTwo Regulatory T-Cell Subsets Enhanced Interleukin-15 Efficacy in a Prostate Tumor Model”, Proceedings of the National Academy of Sciences of the United States of Ame…
[cited by applicant]
Yu et al. (Dec. 15, 2010), e-Published (Oct. 5, 2010) “Simultaneous Blockade of Multiple Immune System Inhibitory Checkpoints Enhances Antitumor Activity Mediated by Interleukin-15 in a Murine Metastto Colon Crcinoma Mo…
[cited by applicant]