Granted Patent
B2
US 12,458,639 · App. 18/306,191 · Granted Nov 4, 2025
Tubulin binding compounds and therapeutic use thereof
Inventors:
Lan Huang (New York, NY); Santosh Ambadas Khedkar (Lexington, MA); Michel O. Steinmetz (Villigen, CH)
Assignee:
BeyondSpring Pharmaceuticals, Inc.
View Patent ↗
Loading inventors, assignments & file history…
Abstract
Disclosed herein are compounds that can bind to tubulin and activate GEF-H1. Methods of using these compounds for treating cancer are also disclosed.
Claims (5)
1 . A method of treating or inhibiting the progression of cancer selected from the group consisting of breast cancer, colon cancer, rectal cancer, lung cancer, prostate cancer, melanoma, leukemia, ovarian cancer, gastric cancer, renal cell carcinoma, liver cancer, pancreatic cancer, lymphomas and myeloma, the method comprising:
administering to a subject in need thereof a compound selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
2 . A pharmaceutical composition comprising a pharmaceutically acceptable excipient, and a compound selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Jul 9, 2025
From: HUANG, LAN; KHEDKAR, SANTOSH AMBADAS; STEINMETZ, MICHAEL O.
To: BEYONDSPRING PHARMACEUTICALS, INC.
Reel/Frame 071647/0673 →
Continuity (3)
Division
16476242
Provisional Application
62443247
· Jan 6, 2017
References Cited (400)
US 4410537A
· Kneen
· 1983
[cited by applicant]
US 4535183A
· Kneen
· 1985
[cited by applicant]
US 5607934A
· Tone et al.
· 1997
[cited by applicant]
US 5733888A
· Bryans et al.
· 1998
[cited by applicant]
US 5852018A
· Bryans et al.
· 1998
[cited by applicant]
US 5872151A
· Rhodes
· 1999
[cited by applicant]
US 5874443A
· Kiely et al.
· 1999
[cited by applicant]
US 5886210A
· Rayle et al.
· 1999
[cited by applicant]
US 5891877A
· Brocchini et al.
· 1999
[cited by applicant]
US 5922683A
· Or et al.
· 1999
[cited by applicant]
US 5939098A
· Reidenberg et al.
· 1999
[cited by applicant]
US 5958980A
· Rhodes
· 1999
[cited by applicant]
US 6069146A
· Fenical et al.
· 2000
[cited by applicant]
US 6096786A
· Rhodes
· 2000
[cited by applicant]
US 6350759B1
· Casara et al.
· 2002
[cited by applicant]
US 6358957B1
· Fukumoto et al.
· 2002
[cited by applicant]
US 6500825B2
· Lan et al.
· 2002
[cited by applicant]
US 6506787B2
· Fujishita et al.
· 2003
[cited by applicant]
US 6509331B1
· Audia et al.
· 2003
[cited by applicant]
US 6583143B2
· Haddach
· 2003
[cited by applicant]
US 6713480B2
· Fukumoto et al.
· 2004
[cited by applicant]
US 6808710B1
· Wood et al.
· 2004
[cited by applicant]
US 6972289B1
· Kanzaki et al.
· 2005
[cited by applicant]
US 7026322B2
· Hayashi et al.
· 2006
[cited by applicant]
US 7064201B2
· Hayashi et al.
· 2006
[cited by applicant]
US 7488802B2
· Collins et al.
· 2009
[cited by applicant]
US 7629380B2
· McMorris et al.
· 2009
[cited by applicant]
US 7635757B2
· Freeman et al.
· 2009
[cited by applicant]
US 7674903B2
· Hayashi et al.
· 2010
[cited by applicant]
US 7700615B2
· Edwards et al.
· 2010
[cited by applicant]
US 7919497B2
· Palladino et al.
· 2011
[cited by applicant]
US 7935704B2
· Palladino et al.
· 2011
[cited by applicant]
US 7943743B2
· Korman et al.
· 2011
[cited by applicant]
US 7956058B2
· Hayashi et al.
· 2011
[cited by applicant]
US 8008449B2
· Korman et al.
· 2011
[cited by applicant]
US 8129527B2
· Palladino et al.
· 2012
[cited by applicant]
US 8168757B2
· Finnefrock et al.
· 2012
[cited by applicant]
US 8217149B2
· Irving et al.
· 2012
[cited by applicant]
US 8247552B2
· Palladino et al.
· 2012
[cited by applicant]
US 8618292B2
· Palladino et al.
· 2013
[cited by applicant]
US 9358289B2
· Korman et al.
· 2016
[cited by applicant]
US 9394368B2
· Brogdon et al.
· 2016
[cited by applicant]
US 20020028819A1
· Teng et al.
· 2002
[cited by applicant]
US 20020143021A1
· Fukumoto et al.
· 2002
[cited by applicant]
US 20040176372A1
· Suto et al.
· 2004
[cited by applicant]
US 20060079534A1
· Kanzaki et al.
· 2006
[cited by applicant]
US 20060167010A1
· Hayashi et al.
· 2006
[cited by applicant]
US 20060223822A1
· Hayashi et al.
· 2006
[cited by applicant]
US 20070293453A1
· Fisher et al.
· 2007
[cited by applicant]
US 20080199485A1
· Kundig et al.
· 2008
[cited by applicant]
US 20080255035A1
· Trieu et al.
· 2008
[cited by applicant]
US 20090170837A1
· Gourdeau et al.
· 2009
[cited by applicant]
US 20120041070A1
· Shengfan et al.
· 2012
[cited by applicant]
US 20130131018A1
· Leblond et al.
· 2013
[cited by applicant]
US 20150202291A1
· Bosch et al.
· 2015
[cited by applicant]
US 20160243153A1
· Sundaram et al.
· 2016
[cited by applicant]
US 20180028531A1
· Huang et al.
· 2018
[cited by applicant]
US 20200129504A1
· Mohanlal et al.
· 2020
[cited by applicant]
US 20200281921A1
· Huang
· 2020
[cited by applicant]
US 20210030843A1
· Mohanlal
· 2021
[cited by applicant]
US 20210161888A1
· Huang et al.
· 2021
[cited by applicant]
US 20210177952A1
· Mohanlal et al.
· 2021
[cited by applicant]
US 20220387365A1
· He
· 2022
[cited by applicant]
US 20230035763A1
· Tonra
· 2023
[cited by applicant]
US 20230181605A1
· Mohanlal et al.
· 2023
[cited by applicant]
US 20240197723A1
· Huang
· 2024
[cited by applicant]
CN 110240592
· 2017
[cited by applicant]
EA 010198B1
· 2008
[cited by applicant]
EA 016817B1
· 2012
[cited by applicant]
EP 0054924
· 1982
[cited by applicant]
EP 0655060
· 1998
[cited by applicant]
GB 2143823
· 1985
[cited by applicant]
JP 059164
· 1993
[cited by applicant]
JP 05255106
· 1993
[cited by applicant]
JP 10130266
· 1998
[cited by applicant]
JP 2002507612A
· 2002
[cited by applicant]
JP 2012144512
· 2012
[cited by applicant]
JP 2013501791
· 2013
[cited by applicant]
JP 2014508167
· 2014
[cited by applicant]
JP 2015030679
· 2015
[cited by applicant]
JP 2016516523
· 2016
[cited by applicant]
JP 2016518879
· 2016
[cited by applicant]
JP 2018036233
· 2018
[cited by applicant]
RU 2258702
· 2005
[cited by applicant]
RU 2011148945A
· 2010
[cited by applicant]
WO WO8705297
· 1987
[cited by applicant]
WO WO9407479
· 1994
[cited by applicant]
WO WO9506077
· 1995
[cited by applicant]
WO WO9521832
· 1995
[cited by applicant]
WO WO9620190
· 1996
[cited by applicant]
WO WO9938844
· 1999
[cited by applicant]
WO WO99048889
· 1999
[cited by applicant]
WO WO00012121
· 2000
[cited by applicant]
WO WO01053290
· 2001
[cited by applicant]
WO WO01070663
· 2001
[cited by applicant]
WO WO03074550
· 2003
[cited by applicant]
WO WO03097164
· 2003
[cited by applicant]
WO WO04016600
· 2004
[cited by applicant]
WO WO04054498
· 2004
[cited by applicant]
WO WO04093831
· 2004
[cited by applicant]
WO WO05077940
· 2005
[cited by applicant]
WO WO06121168
· 2006
[cited by applicant]
WO WO07035841
· 2007
[cited by applicant]
WO WO07113648
· 2007
[cited by applicant]
WO WO08128169
· 2008
[cited by applicant]
WO WO09064444
· 2009
[cited by applicant]
WO WO09089260
· 2009
[cited by applicant]
WO WO10001169
· 2010
[cited by applicant]
WO WO10083439
· 2010
[cited by applicant]
WO WO10101627
· 2010
[cited by applicant]
WO WO11034954
· 2011
[cited by applicant]
WO WO11050344
· 2011
[cited by applicant]
WO WO11066389
· 2011
[cited by applicant]
WO WO11079507
· 2011
[cited by applicant]
WO WO11109625
· 2011
[cited by applicant]
WO WO11146382
· 2011
[cited by applicant]
WO WO11151423
· 2011
[cited by applicant]
WO WO12014549
· 2012
[cited by applicant]
WO WO12035436
· 2012
[cited by applicant]
WO WO12074904
· 2012
[cited by applicant]
WO WO12145493
· 2012
[cited by applicant]
WO WO13078537
· 2013
[cited by applicant]
WO WO13090552
· 2013
[cited by applicant]
WO WO13177633
· 2013
[cited by applicant]
WO WO14036412
· 2014
[cited by applicant]
WO WO14066834
· 2014
[cited by applicant]
WO WO14130657
· 2014
[cited by applicant]
WO WO14160183
· 2014
[cited by applicant]
WO WO14183066
· 2014
[cited by applicant]
WO WO14195852
· 2014
[cited by applicant]
WO WO15069770
· 2015
[cited by applicant]
WO WO15069790
· 2015
[cited by applicant]
WO WO15160641
· 2015
[cited by applicant]
WO WO16081281
· 2016
[cited by applicant]
WO WO16165007
· 2016
[cited by applicant]
WO WO17062505
· 2017
[cited by applicant]
WO WO19194738
· 2019
[cited by applicant]
WO WO21225908
· 2021
[cited by applicant]
“Definition of ‘within’”. [Online] [2015 Archived version accessed on Aug. 13, 2020 from |https://web.archive.org/web/20151030162428/ https://dictionary.cambridge.org/us/dictionary/english/within. Cambridge English Dict…
[cited by applicant]
Abels, Christoph, Targeting of the Vascular System of Solid Tumours by Photodynamic Therapy (PDT), Photochem Photobiol Sci., (Mar. 2004) 3: 765-771.
[cited by applicant]
Abolhasani et al., Jan. 2015, In-silico investigation of tubulin binding modes of a series of novel antiproliferative spiroisoxazoline compounds using docking studies, Iranian Journal of Pharmaceutical Research, 14(1):1…
[cited by applicant]
Abstracts of The 1999 Joint Chubu and Kansai Branch Conference and Symposia of Japan Society for Bioscience, Biotechnology, and Agrochemistry, (1999) p. 48.
[cited by applicant]
Acquaviva et al., “Targeting KRAS-Mutant Non-Small Cell Lung Cancer with the Hsp90 Inhibitor Ganetespib”, Mol Cancer Ther, Dec. 2012, 11(12), pp. 2633-2643.
[cited by applicant]
Agarwal et al., “OP449, a Novel SET Antagonist, Is Cytotoxic To Leukemia Cells and Enhances Efficacy of Tyrosine Kinase Inhibitors in Drug-Resistant Myeloid Leukemias,” pursuant to an EMBASE record for a Conference Abst…
[cited by applicant]
Aggarwal et al., Antiangiogenic agents in the management of non-small cell lung cancer: Where do we stand now and where are we headed? Cancer Biology & Therapy (2012), 13(5), 247-263.
[cited by applicant]
Ahmed et al. “A new rapid and simple non-radioactive assay to monitor and determine the proliferation of lymphocytes: an alternative to [
[cited by applicant]
Akerlund et al., “Diketopiperazine-Based Polymers from Common Amino Acids,” Journal of Applied Polymer Science, (2000) 78 (12), 2213-2218.
[cited by applicant]
Algaier et al. “The effects of dimethyl sulfoxide on the kinetics of tubulin assembly.” Biochim. Biophys. Acta. 954, 235-43 (1988).
[cited by applicant]
Ali et al. “Toxicity of echinulin from Aspergillus chevalieri in rabbits.” Toxicology Letters. (1989) 48: 235-41.
[cited by applicant]
Asahina, T., “Spectrochemical Study of Amino-acid Anhydrides,” Bulletin of the Chemical Society of Japan, (1930) 5, 354-365.
[cited by applicant]
Augustin, M. “Die Umsetzung des 2,5-Diketopiperazins mit Aldehyden und Nitrosoverbindungen” Journal für Praktische Chemie, (1966) 32(4), 158-166.
[cited by applicant]
Aviel-Ronen et al., “K-ras Mutations in Non-Small-Cell Lung Carcinoma: A Review,”
[cited by applicant]
Bankowska et al., Derivatives of 1,2,3-triazole. Potential drugs?, Wiadomosci Chemiczne (2012), 66(11-12), 993-1022.
[cited by applicant]
Beavis et al., “Dual PD-1 and CTLA-4 Checkpoint Blockade Promotes Antitumor Immune Responses through CD4
[cited by applicant]
Bergman et al., Ariloxy Substituted N-arylpiperazinones as Dual Inhibitors of Farnesyltransferase and Geranylgeranyltransferase-1, Bioorg & Med Chem Lttrs. (Mar. 2001) 11: 1411-1415.
[cited by applicant]
Bertelsen et al., “Vascular effects of plinabulin (NPI-2358) and the influence on tumour response when given alone or combined with radiation,” International Journal of Radiation Biology (2011), 87(11), 1126-1134.
[cited by applicant]
Bertino J., et al., “Principles of Cancer Therapy.” Cecil Textbook of Medicine. Eds. Lee Goldman, et al. 21nd ed., (2000), Chapter 198, pp. 1060-1074.
[cited by applicant]
Blayney et al., “Plinabulin, a Novel Small Molecule That Ameliorates Chemotherapy-Induced Neutropenia, Is Administered on the Same Day of Chemotherapy and Has Anticancer Efficacy”, Meeting Info.: 58th Annual Meeting and…
[cited by applicant]
Bond et al. “The Synthesis of Viridamine, a Penicillium Viridicatum Mycotoxin.” Synthetic Commun. 19 (13&14), 2551-2566 (1989).
[cited by applicant]
Borisy, G.G. “A Rapid Method for Quantitative Determination of Microtubule Protein using DEAE-Cellulose Filters.” Anal. Biochem. 50, 373-385 (1972).
[cited by applicant]
Braga et al. “Crystal Polymorphism and Multiple Crystal Forms,” Struct Bond (2009) 132:25-50.
[cited by applicant]
Brahmer et al., “Safety and Activity of Anti-PD-L1 Antibody in Patients with Advanced Cancer,” N Engl J Med (2012) 366:2455-2465.
[cited by applicant]
Buchbinder et al., Feb. 2016, CTLA-4 and PD-1 pathways: similarities, differences, and implications of their inhibition, American Journal of Clinical Oncology, 39(1):98-106.
[cited by applicant]
Burtles, Sally, “Transition from Preclinical to first-in-man Phase”, Expert Scientific Group on Phase One Clinical Trials Final Report, Presentation Jun. 19, 2006, pp. 35-38.
[cited by applicant]
Cai, Small molecule vascular disrupting agents: potential new drugs for cancer treatment, a 2009 update, Frontiers in Anti-Cancer Drug Discovery (2010), 1, 380-427.
[cited by applicant]
Cai, Sui X., “Small Molecule Vascular Disrupting Agents: Potential New Drugs for Cancer Treatment”, Recent Pat Anticancer Drug Discov. (2007) 2(1): 79-101.
[cited by applicant]
Caira, 1998, Crystalline polymorphism of organic compounds, Topics in Current Chemistry, 198:163-208.
[cited by applicant]
Callahan et al., “At the Bedside: CTLA-4- and PD-1-blocking antibodies in cancer immunotherapy”, J Leukocyte Biol, vol. 94, Jul. 2013, pp. 41-53.
[cited by applicant]
Carter et al., “No patient left behind: The promise of immune priming with epigenetic agents,” Oncoimmunology (2017) vol. 6, No. 10, e1315486 (13 pages).
[cited by applicant]
Chaplin et al., “Antivascular approaches to solid tumour therapy: evaluation of tubulin binding agents”, Br. J. Cancer 1996, 74 (Suppl. XXVII), S86-S88.
[cited by applicant]
Chen et al., “Adjuvant effect of docetaxel on the immune responses to influenza A H1N1 vaccine in mice,” BMC Immunology (2012) 13:36, pp. 1-12.
[cited by applicant]
Chin et al., “Immune Intervention with Monoclonal Antibodies Targeting CD152 (CTLA-4) for Autoimmune and Malignant Diseases,” Chang Gung Med J (Jan.-Feb. 2008) vol. 31, No. 1, pp. 1-15.
[cited by applicant]
ClinicalTrials.gov Identifier NCT00892931, “Phase 2 study MPC-6827 for recurrent glioblastoma multiforme,” (Oct. 14, 2011). [retrieved from internet on Jul. 30, 2019] <URL: https://clinicaltrials.gov/ct2/show/NCT0089293…
[cited by applicant]
ClinicalTrials.gov Identifier NCT02846792, “Nivolumab and Plinabulin in Treating Patients With Stage IIIB-IV, Recurrent, or Metastatic Non-small Cell Lung Cancer,” (Jul. 27, 2016). [retrieved from internet on Sep. 17, 2…
[cited by applicant]
ClinicalTrials.gov Identifier NCT03294577, “Plinabulin vs. pegfilgrastim in prevention of TAC induced neutropenia” (Sep. 27, 2107). <URL:ttps://clinicaltrials.gov/ct2/show/NCT3294577> 4 pp.
[cited by applicant]
Cole, P., “Durvalumab, Human anti-PD-L1 monoclonal antibody Immune checkpoint inhibitor Oncolytic”, Drugs of the Future 2014, 39(12): pp. 843-847.
[cited by applicant]
Collins et al., 2014, Lipid tucaresol as an adjuvant for methamphetamine vaccine development, CHemComm, 50:4079-4081.
[cited by applicant]
Cooper et al., “Response to BRAF Inhibition in Melanoma Is Enhanced When Combined with Immune Checkpoint Blockade,” Published OnlineFirst Apr. 29, 2014; DOI: 10.1158/2326-6066.CIR-13-0215; Cancer Immunol Res (Jul. 2014)…
[cited by applicant]
Costa et al., “Analyses of selected safety endpoints in phase 1 and late-phase clinical trials of anti-PD-1 and PD-L1 inhibitors: prediction of immune-related toxicities,” Oncotarget (2017) vol. 8, No. 40, pp. 67782-677…
[cited by applicant]
Crawford, Aug. 2003, Once-per-cycle pegilgrastim (neulata) for the management of chemotherapy-induced neutropenia, Seminars in Oncology 30(4)Suppl 13:23-30.
[cited by applicant]
Cui et al. “Novel Mammalian Cell Cycle Inhibitors, Tryprostatins A, B and Other Diketopiperazines Produced by Aspergillus fumigatus.” J. Antibiotics. 49(6), 534-40 (1996).
[cited by applicant]
Cui et al. “Novel Mammalian Cell Cycle Inhibitors, Tryprostatins A, B and Other Diketopiperazines Produced by Aspergillus fumigatus.” J. Antibiotics. 49(6): 527-33 (1996).
[cited by applicant]
Dale, Oct. 2015, Neutropenia, John Wiley & Sons Ltd., www.els.net, 8 pp.
[cited by applicant]
Dalgleish, 2015, Rationale for combining immunotherapy with chemotherapy, Immunotherapy, 7(3):309-316.
[cited by applicant]
Das et al., Feb. 1, 2015, Combination therapy with anti-CLTA4 and antiPD1 leads to distinct immunologic changes in-vivo, J. Immunolog, 194(3):950-959.
[cited by applicant]
Davis et al., ZD6126: A Novel Vascular-targeting Agent That Causes Selective Destruction of Tumor Vasculature, Cancer Research (Dec. 15, 2002) 62: 7247-7253.
[cited by applicant]
Dorwald, F., “Side Reactions in Organic Synthesis” Wiley-VCH Verlag Gmbh & Co. KgaA, Weinheim, (2005), book cover and preface p. IX only.
[cited by applicant]
Drug Approval And Licensing Procedures in Japan 2001, 2001, pp. 243-244.
[cited by applicant]
Dunitz et al., “Disappearing Polymorphs,” Acc. Chem. Res. (1995) vol. 28, No. 4, pp. 193-200.
[cited by applicant]
Fernandez-Medarde et al., Mar. 2011, Ras in cancer and developmental diseases, Genes & Cancer, 2(3):344-358.
[cited by applicant]
Fernandez-Tejada et al., 2014, Design, synthesis, and immunologic evaluation of vaccine adjuvant conjugates based on QS-21 and tucaresol, Bioorganic & Medicinal Chemistry, 22:5917-5923.
[cited by applicant]
Fernandez-Tejada et al., 2016, Development of improved vaccine adjuvants based on the saponin natural product QS-21 through chemical synthesis, Accounts of Chemical Research 49:1741-1756.
[cited by applicant]
Ferrer et al., Plinabulin: tubulin polymerization inhibitor vascular-disrupting agent oncolytic, Drugs of the Future (2010), 35(1), 11-15.
[cited by applicant]
Fessas et al., 2017, A molecular and preclinical comparsion of the PC-1-targeted t-cell checkpoint inhibitors nivolumab and mebrolizumag, Seminars in Oncology, 44:136-140.
[cited by applicant]
Field et al., 2014, Microtubule-targeting agents are clinically successful due to both mitotic and interphase impairment of microtubule function, Bioorganic & Medicinal Chemistry, 22:5050-5059.
[cited by applicant]
Folkes et al., Synthesis and In Vitro Evaluation of a Series of Diketopiperazine Inhibitors of Plasminogen Activator Inhibitor-1, Bioorg & Med Chem Lttrs., (Jul. 2001) 11: 2589-2592.
[cited by applicant]
Folkman, Dec. 2002, Role of angiogenesis in tumor growth and metastasis, Semin Oncol, 29:15-18.
[cited by applicant]
Frost et al., Novel Syngeneic Pseudo-orthotopic Prostate Cancer Model: Vascular, Mitotic and Apoptotic Responses to Castration, Microvasc Research (Dec. 2004) 69: 1-9.
[cited by applicant]
Fukushima et al., “Biological Activities of Albonoursin,” J. Antibiotics, (1973) 26:175.
[cited by applicant]
Gallina et al., “Condensation of 1,4-diacetylpiperazine-2,5-dione with aldehydes”, Tetrahedron 1974, 30, 667-673.
[cited by applicant]
Gameiro et al., “Exploitation of differential homeostatic proliferation of T-cell subsets following chemotherapy to enhance the efficacy of vaccine-mediated antitumor responses,” Cancer Immunology Immunotherapy (2011) v…
[cited by applicant]
Garris et al., “Successful Anti-PD-1 Cancer Immunotherapy Requires T Cell-Dendritic Cell Crosstalk Involving the Cytokines IFN-( and IL-12,” Immunity (Dec. 18, 2018) 49, pp. 1-14, e1-e7 (22 pages).
[cited by applicant]
Goldani et al. “Treatment of murine pulmonary mucormycosis with SCH 42427, a broad-spectrum triazole antifungal drug”, Correspondence, J Antimicrob Chemother. 33, 369-372 (1994).
[cited by applicant]
Goldfarb et al., “Synthesis of β-2-thienylalanine,” Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, (1958) 98-100, as abstracted by Caplus.
[cited by applicant]
Gordon et al. “Reductive Alkylation on a Solid Phase: Synthesis of a Piperazinedione Combinatorial Library.” J. Bioorg. Med. Chem. Letters. 5, 47-50 (1995).
[cited by applicant]
Granville et al., Release of Cytochrome c1 Bax Migration, Bid Cleavage, and Activation of Caspases 2, 3, 6, 7, 8, and 9 during Endothelial Cell Apoptosis, Am J Path., (Oct. 1999) 155(4): 1021-1025.
[cited by applicant]
Gridelli et al., Vascular disrupting agents: a novel mechanism of action in the battle against non-small cell lung cancer, Oncologist (2009), 14(6), 612-620.
[cited by applicant]
Gu et al., “Identification of CTLA-4 isoforms produced by alternative splicing and their association with myasthenia gravis,” Clinical Immunology (Sep. 2008) vol. 128, Issue 3, pp. 374-381.
[cited by applicant]
Gura, Trisha, “Cancer Models: Systems for Identifying New Drugs are Often Faulty”, Science 7(Nov. 1997) 278(5340): 1041-1042.
[cited by applicant]
Hamel, E. “Antimitotic Natural Products and Their Interactions with Tubulin.” Med. Res. Rev. (1996) 16(2): 207-31.
[cited by applicant]
Hartwell et al. “Checkpoints: Controls that Ensure the Order of Cell Cycle Events.” Science. 246, 629-34 (1989).
[cited by applicant]
Hayakawa, Structure-activity relationship analysis, Japanese Journal of Cancer and Chemotherapy, (2004), 31(4):526-528.
[cited by applicant]
Hayashi et al., “Total Synthesis of Anti-microtubule Diketopiperazine Derivatives: Phenylahistin and Aurantiamine,” J. Org. Chem., (2000) 65: 8402-8405.
[cited by applicant]
Hayashi et al., Medicinal chemistry and chemical biology of diketopiperazine-type antimicrotubule and vascular-disrupting agents, Chemical & Pharmaceutical Bulletin (2013), 61(9), 889-901.
[cited by applicant]
Hayashi et al., Small peptide-based medicinal chemistry for intractable disease, Peptide Science (2009), Volume Date 2008, 45th, 139-140.
[cited by applicant]
He et al., “Low-dose paclitaxel enhances the anti-tumor efficacy of GM-CSF surface-modified whole-tumor-cell vaccine in mouse model of prostate cancer,” Cancer Immunology Immunotherapy (2011) vol. 60, No. 5, pp. 715-730…
[cited by applicant]
Heist et al., “Abstract C30: Phase 1/2 study of the vascular disrupting agent (VCA) plinabulin (NPI-2358) combined with docetaxel in patients with non-small cell lung cancer (NSCLC),” Mol. Cancer Ther., 2009; 8(12 Suppl…
[cited by applicant]
Heist et al., “Randomized Phase 2 Trial of Plinabulin (NPI-2358) Plus Docetaxel in Patients with Advanced Non-Small Lung Cancer (NSCLC),” 2014 ASCO Annual Meeting. . (abstr 8054) Poster Presentation. Retrieved from the …
[cited by applicant]
Heist et al., “Randomized phase 2 trial of plinabulin (NPI-2358) plus docetaxel in patients with advanced non-small cell lung cancer (NSCLC).” J. Clin. Oncol. (2014) vol. 32, No. 5s, (suppl; abstr 8054).
[cited by applicant]
Helleman et al. “The International Journal of Biochemistry & Cell Biology,” vol. 42, pp. 25-30 (2010).
[cited by applicant]
Hellmann et al., Nov. 21, 2019, Nivolumab plus ipilimumab in advanced non-small-cell lung cancer, The New England Journal of Medicine, 381:2020-2031.
[cited by applicant]
Hodi et al., Nov. 2016, Combined nivolumab and ipilimumab versus ipilimumab alone in patients with advanced melanoma: 2-year overall survival outcomes in a multicentre, randomised, controlled, phase 2 trial, Lancet Onco…
[cited by applicant]
Horak et al. “Structures of the Austalides A-E, Five Novel Toxic Metabolites from Aspergillus ustus.” J Chem Soc Chem Commun. (1981) 1265-67.
[cited by applicant]
http://scienceandresearch.homeoffice.gov.uk/animal-research/publications-and-reference/001-abstracts/abstracts2-2006/02november-2006/457?view=Html; “Abstract #457, Animals in Scientific Procedures (2006)”; (accessed on …
[cited by applicant]
Hursthouse et al., “Why Do Organic Compounds Crystallise Well or Badly or Ever so Slowly? Why Is Crystallisation Nevertheless Such a Good Purification Technique?,” Organic Process Res & Devel (2009) vol. 13, No. 6, pp. …
[cited by applicant]
Hwang et al., 2019, Heat shock proteins: a dual carrier-adjuvant for an anti-drug vaccine against heroin, Bioorganic & Medicinal Chemistry, 27:125-132.
[cited by applicant]
Hyun et al., “Valine dehydrogenase from Streptomyces albus: gene cloning, heterologous expression and identification of active site by site-directed mutagenesis,” FEMS Microbiology Letters (Jan. 1, 2000) 182: 29-34.
[cited by applicant]
Intlekofer et al., Jul. 2013, At the bench: preclinical rationale for CTLA-4 and PD-1 blockade as cancer immunotherapy, J. Leukoc Biol., 94(1):25-39.
[cited by applicant]
Iwasaki, S. “Antimitotic Agents: Chemistry and Recognition of Tubulin Molecule.” Med Res Rev. (1993) 13: 183-198.
[cited by applicant]
Iwasaki, S. “Bioactive Natural Products Interfering with Microtubule Function.” Kagaku to Seibutsu. 32(3): 153-159 (1994).
[cited by applicant]
Ji et al., Tubulin Colchicine Binding Site Inhibitors as Vascular Disrupting Agents in Clinical Developments, Current Medicinal Chemistry (2015), 22(11), 1348-1360.
[cited by applicant]
Jiang et al., “A Novel Peptide Isolated from a Phage Display Peptide Library with Trastuzumab Can Mimic Antigen Epitope of HER-2*,” (Feb. 11, 2005) J Biol Chem, vol. 280, No. 6, pp. 4656-4662.
[cited by applicant]
Johnson et al. “Kinetic Analysis of Microtubule Self-assembly in Vitro.” J. Mol. Biol. 117, 1-31 (1977).
[cited by applicant]
Jure-Kunkel M. et al., “Synergy between chemotherapeutic agents and CTLA-4 blockade in preclinical tumor models”, Cancer Immunol. Immunother. 2013, vol. 62, pp. 1533-1545.
[cited by applicant]
Kakoulidou et al., “Human Soluble CD80 is Generated by Alternative Splicing, and Recombinant Soluble CD80 Binds to CD28 and CD152 Influencing T-cell Activation,” Scandinavian J. Immunol (Nov. 2007) 66(5):529-537.
[cited by applicant]
Kamb, Alexander, “What's wrong with our cancer models?”, Nature Reviews Drug Discovery (Feb. 2005) 4: 161-165.
[cited by applicant]
Kanoh et al., “(−)-Phenylahistin: A New Mammalian Cell Cycle Inhibitor Produced by Aspergillus USTUS,” Bioorganic & Medicinal Chemistry Letters, (1997) 7: 2847-2852.
[cited by applicant]
Kanoh et al., “(−)-Phenylahistin Arrests Cells in Mitosis by Inhibiting Tubulin Polymerization,” The Journal of Antibiotics, (1999) 52: 134-141.
[cited by applicant]
Kanoh et al., “Antitumor Activity of Phenylahistin in Vitro and in Vivo,” Bioscience Biotechnology Biochemistry, (1999) 63(6): 1130-1133.
[cited by applicant]
Kanoh et al., “Synthesis and Biological Activities of Phenylahistin Derivatives,” Bioorganic & Medicinal Chemistry, (1999) 7: 1451-1457.
[cited by applicant]
Kanojia et al., May 2015, βIII-tubulin regulates breast cancer meastases to the brain, Mol Cancer Ther., 14(5):1152-1161.
[cited by applicant]
Kanthou et al., Microtubule depolymerizing vascular disrupting agents: novel therapeutic agents for oncology and other pathologies, International Journal of Experimental Pathology(2009), 90(3), 284-294.
[cited by applicant]
Kanzaki et al., A Novel Potent Cell Cycle Inhibitor Dehydrophenylahistin-Enzymatic Synthesis and Inhibitory Activity toward Sea Urchin Embryo, The Journal of Antibiotics, (Dec. 2002) 55(12):1042-1047.
[cited by applicant]
Kanzaki et al., “Effective Production of Dehydro Cyclic Dipeptide Albonoursin Exhibiting PronuclearFusion Inhibitory Activity, I. Taxonomy and Fermentation,” The Journal of Antibiotics, (1999) 52: 1017-1022.
[cited by applicant]
Kanzaki et al., “Effective Production of Dehydro Cyclic Dipeptide Albonoursin Exhibiting Pronuclear Fusion Inhibitory Activity, II. Biosynthetic and Bioconversion Studies,” The Journal of Antibiotics, (2000) 53(1): 58-6…
[cited by applicant]
Kanzaki et al., “Enzymatic dehydrogenation of cyclo(L-Phe-L-Leu) to a bioactive derivative, albonoursin,” Journal of Molecular Catalysis B: Enzymatic (1999) 6(3): 265-270.
[cited by applicant]
Kanzaki et al., “Enzymatic Synthesis of Physiologically Active Substances Utilizing a Novel System for the Synthesis of Diketopiperazines Comprising Dehydroamino Acids as Constituents,” Abstracts of Papers Presented at …
[cited by applicant]
Kanzaki et al., “Novel Cyclic Dipeptide Dehydrogenase and Assay Method for Its Activity,” Scientific Reports of the Faculty of Agriculture, Okayama University, (1999) 88: 7-11.
[cited by applicant]
Kashyap et al., Sep. 24, 2019, GEF-H1 signaling upon microtubule destabilization is required for dendritic cell activation and specific anti-tumor responses, Cell Reports, 28:3367-3380.
[cited by applicant]
Keepers et al. “Comparison of the Sulforhodamine B Protein and Tetrazolium (MTT) Assays for in vitro Chemosensitivity Testing.” Eur. J. Cancer. 27, 897-900 (1991).
[cited by applicant]
Kim et al. “Polymer attached cyclic peptides, tetrahedron: Asymmetry.” 3(11):1421-1430 (1992).
[cited by applicant]
Kingston, Correction to Tubulin-interactive natural products as anticancer agents, Journal of Natural Products (2011), 74(5), 1352.
[cited by applicant]
Kingston, Tubulin-Interactive Natural Products as Anticancer Agents, Journal of Natural Products (2009), 72(3), 507-515.
[cited by applicant]
Kobayashi et al., “Microtubule Assembly Regulators of Microbial Origin,” Abstract of Paper Read at the 1989 Symposium on the Chemistry of Natural Products, (1989) 51.
[cited by applicant]
Kola et al., “Can the pharmaceutical industry reduce attrition rates?”, Nature Reviews Drug Discovery (2004) 3: 711-715.
[cited by applicant]
Kondoh et al. “Effects of Tryprostatin Derivatives on Microtubule Assembly In Viro and In Situ.” J. Antibiotics. 51, 801-04 (1998).
[cited by applicant]
Kopple et al., “A Convenient Synthesis of 2,5-Piperazinediones 1a,” The Journal of Organic Chemistry, (1967) 33: 862-864.
[cited by applicant]
Kreamer K., “Immune checkpoint blockade: A New Paradigm in Treating Advanced Cancer”, J. Adv. Pract. Oncol., 2014, vol. 5, pp. 418-431.
[cited by applicant]
Krendel et al., Apr. 2002, Nucelotide exchange factor GEF-H1 mediates cross-talk between microtubules and the actin cytoskeleton, Nature Cell Biology, 4:294-301 and supplementary information.
[cited by applicant]
Krishan, A. “Rapid Flow Cytofluorometric Analysis of Mammalian Cell Cycle By Propidium lodide Staining.” J. Cell Biol. 66, 188-193 (1975).
[cited by applicant]
Kupchan et al. “Steganacin and Steganangin, Novel Antileukemic Lignan Lactones from Steganotaenia araliacea 1-3.” J. Am. Chem. Soc. (1973) 95(4): 1335-36.
[cited by applicant]
Küster & Koeppenhöfer, “Über eininge Pyrrolderivate,” Z. Physiol, Chem., (1927) 172:126-137.
[cited by applicant]
Lacey et al. “Interaction of Phomopsin A and Related Compounds with Purified Sheep Brain Tubulin.” Biochem. Pharmacol. 36, 2133-38 (1987).
[cited by applicant]
Laemmli, U.K. “Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4.” Nature. 227, 680-85 (1970).
[cited by applicant]
Larsen et al. “Aurantiamine, A Kiketopiperazine from Two Varieties of Penicillium Aurantiogriseum.” Phytochemistry. 31, 1613-1615 (1992).
[cited by applicant]
Leaf, Clifton, “Why are we losing the war on cancer (And how to win it)?”, Health Administrator (2005) XVII(1): 172-183.
[cited by applicant]
Lee et al. “The Reconstitution of Microtubules from Purified Calf Brain Tubulin.” Biochemistr. 14(23), 5183-87 (1975).
[cited by applicant]
Lee et al., “A practical guide to pharmaceutical polymorph screening & selection,” Asian Journal of Pharmaceutical Sciences (2014) vol. 9, pp. 163-175.
[cited by applicant]
Lee et al., Colchicine site inhibitors of microtubule integrity as vascular disrupting agents, Drug Development Research (2008), 69(6), 352-358.
[cited by applicant]
Li et al., May-Jun. 2017, Epitope mapping reveals the binding mechanism of a functional antibody cross-reactive to both human and murine programmed death 1, MABS, 9(4):628-637.
[cited by applicant]
Li, Y., et al. “Interaction of marine toxin dolastatin 10 with porcine brain tubulin: competitive inhibition of rhizoxin and phomopsin A binding.” Chem. Biol. Interact. 93, 175-83 (1994).
[cited by applicant]
Liao et al., “Design and synthesis of novel soluble 2,5-diketopiperazine derivatives as potential anticancer agents,” European J Med Chem (2014) 83:236-244.
[cited by applicant]
Liou et al., Aug. 12, 2004, Concise synthesis and structure-activity relationships of combretastatin A-4 analogues, 1-aroylindoles and 3-aroylindoles, as novel classes of potent antitubulin agents, Journal of Medicial C…
[cited by applicant]
Liu et al., “The BRAF and MEK Inhibitors Dabrafenib and Trametinib: Effects on Immune Function and in Combination with Immunomodulatory Antibodies Targeting PD-1, PD-L1, and CTLA-4,” Clin Cancer Res (2015) 21(7) 1639-16…
[cited by applicant]
Liwo et al. “Origin of the Ring-Ring Interaction in Cyclic Dipeptides Incorporating an Aromatic Amino Acid.” Tetrahedron Lett. 26, 1873-1876 (1985).
[cited by applicant]
Lloyd et al., 2015, Abstract A184: Activity of plinabulin in tumor models with kras mutations, Mol. Can. Thera. 14(12): Suppl. 2.
[cited by applicant]
Lloyd et al., Abstract A07: Plinabulin: Evidence for an immune-mediated mechanism of action, In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; Jan. 7-10, 2016; San…
[cited by applicant]
Lu et al., Nov. 2012, An overview of tubulin inhibitors that interact with the colchicine binding site, Pharmaceutical Research, 29(11):2943-2971.
[cited by applicant]
Luduena, R.F. “Contrasting Roles of Tau and Microtubule-associated Protein 2 in the Vinblastine-induced Aggregation of Brain Tubulin.” J. Biol. Chem. 259: 12890-98 (1984).
[cited by applicant]
Lyman et al., “Risk Models for Predicting Chemotherapy-Induced Neutropenia,” The Oncologist (2005) 10:427-437.
[cited by applicant]
Lynch et al., “Ipilimumab in Combination With Paclitaxel and Carboplatin As First-Line Treatment in Stage IIIB/IV Non-Small-Cell Lung Cancer: Results From a Randomized, Double-Blind, Multicenter Phase II Study,” (Jun. 1…
[cited by applicant]
Mahindroo et al., “Antitubulin Agents for the Treatment of Cancer—A Medicinal Chemistry Update”, Expert Opin. Ther. Patents (2006) 16(5): 647-691.
[cited by applicant]
Mahoney et al., “The Next Immune-Checkpoint Inhibitors: PD-1/PD-L1 Blockade in Melanoma,” Clinical Therapeutics (Apr. 2015) vol. 37, Issue 4, pp. 764-782. Abstract.
[cited by applicant]
Matsuda et al., “Pilot study of WT1 peptide-pulsed dendritic cell vaccination with docetaxel in esophageal cancer,” Oncology Letters (Jul. 2018) vol. 16, No. 1, pp. 1348-1356.
[cited by applicant]
Melero et al., Aug. 2015, Evolving synergistic combinations of targeted immunotherapies to combat cancer, Nature Reviews Cancer, 15:457-472.
[cited by applicant]
Millward et al., “Phase I trial of NPI-2358 (a novel vascular disrupting agent) plus docetaxel,” J. Clin. Oncol. (May 2009) 27(15S): 3571-3571, Abstract.
[cited by applicant]
Millward et al., “Phase 1 study of the novel vascular disrupting agent plinabulin (NPI-2358) and docetaxel,” The Journal of New Anticancer Agents, vol. 3, No. 30, Feb. 16, 2011 plinabulin (NPI-2358) and docetaxel, Inves…
[cited by applicant]
Mita et al., “Phase 1 First-in-Human Trial of the Vascular Disrupting Agent Plinabulin (NPI-2358) in Patients with Solid Tumors or Lymphomas,” Clinical Cancer Research (2010), 16(23), 5892-5899.
[cited by applicant]
Mita et al., “Phase II study of docetaxel with or without plinabulin (NPI-2358) in patients with non-small cell lung cancer (NSCLC)”,
[cited by applicant]
Mita et al., Randomized Phase 2 Study of Docetaxel +/− Plinabulin (NPI-2358) in Patients with Non-Small Cell Lung Cancer (NSCLC),
[cited by applicant]
Mitsudomi et al., “Mutations of ras genes distinguish a subset of non-small-cell lung cancer cell lines from small-cell lung cancer cell lines,”
[cited by applicant]
Mohanlal et al., “The plinabulin/docetaxel combination to mitigate the known safety concerns of docetaxel,” J Clin Oncol (2016) 34(15_suppl), Abstract e20595.
[cited by applicant]
Mohanlal et al., Feb. 10, 2018, Plinabulin, a novel small molecule clinical stage I0 agent with anti-cancer activity, to prevent chemo-induced neutropenia and immune related AEs, Journal of Clinical Oncology, 36(5 Suppl…
[cited by applicant]
Muguruma et al., OP-20: “Application of Fc-selective Z33-peptide to the preparation of non-covalent-type antibody-antimocrotubule plinabulin conjugate,” 34th European Peptide Symposium 2016 & 8th International Peptide S…
[cited by applicant]
Nabholz, 2001, Phase II study of docetaxel, doxorubiin, and cyclophosphamide as first-line chemotherapy for metastatic breast cancer, Journal of Clinical Oncology, 19:314-321.
[cited by applicant]
Nagaria et al., “Flavopiridol Synergizes with Sorafenib to Induce Cytotoxicity and Potentiate Antitumorigenic Activity in EGFR/HER02 and Mutant RAS/RAF Breast Cancer Model Systems,” Neoplasia (Aug. 2013) vol. 15, No. 8,…
[cited by applicant]
Natoli et al., Mar. 3, 2021. Plinabulin, a distinct microtubule-targeting chemotherapy, promotes M1-like macrophage polarization and anti-tumor immunity, Frontiers in Oncology, 11:1-14.
[cited by applicant]
Neidle, Stephen, ed., Cancer Drug Design and Discovery , 9th Edition, Elsevier/Academic Press, (2008) Chapter 18, pp. 427-431.
[cited by applicant]
Nema et al., Excipients and Their Role in Approved Injectable Products: Current Usage and Future Directions, PDA J Pharm Sci and Tech 2011, 65 287-332.
[cited by applicant]
Neuteboom et al., “450 Poster NPI-2358, a novel tumor vascular disrupting agent potentiates the anti-tumor activity of docetaxel in the non small cell lung cancer model MV522,” EJC Supplements (2008) 6(12):141.
[cited by applicant]
Nicholson et al., NPI-2358 is a tubulin-depolymerizing agent: in-vitro evidence for activity as a tumor vascular-disrupting agent, Anti-Cancer Drugs (2005), Volume Date 2006, 17(1), 25-31.
[cited by applicant]
Nielsen et al., Jun. 2005, Alternative splice variants of the human PD-1 gene, Cell Immunol., 235(2):109-116.
[cited by applicant]
Niemann et al., “The Synthesis of the Three Isomeric dl-β-Pyridylalanines” Journal of the American Chemical Society, (1942) 64(7):1678-1682.
[cited by applicant]
Nihei et al., “Evaluation of antivascular and antimitotic effects of tubulin binding agents in solid tumor therapy”, Jpn. J. Cancer. Res. 1999, 90, 1387-1395.
[cited by applicant]
Nitecki et al., “A Simple Route to Sterically Pure Diketopiperazines1,” The Journal of Organic Chemistry, (1968) 33:864-866.
[cited by applicant]
Ohaegbulam et al., “Human cancer immunotherapy with antibodies to the PD-1 and PD-L1 pathway,” Trends Mol Med, (Oct. 30, 2014) 21(1): pp. 24-33.
[cited by applicant]
Ott et al., “CTLA-4 and PD-1/PD-L1 Blockade: New Immunotherapeutic Modalities with Durable Clinical Benefit in Melanoma Patients,” Clin Cancer Res (Oct. 1, 2013) 19(19): pp. 5300-5309.
[cited by applicant]
Paik et al., “A Phase 2 Study of Weekly Albumin-Bound Paclitaxel (Abraxane®) Given as a Two-Hour Infusion”, Cancer Chemother. Pharmacol., Nov. 2011, vol. 68, No. 5, pp. 1331-1337.
[cited by applicant]
Pardoll et al., “The blockade of immune checkpoints in cancer immunotherapy,” Nat Rev Cancer (May 4, 2016) 12(4): 252-264.
[cited by applicant]
Pattingre et al., “Amino Acids Interfere with the ERK1/2-dependent Control of Macroautophagy by Controlling the Activation of Raf-1 in Human Colon Cancer HT-29 Cells,” J Biol Chem (May 9, 2003) vol. 278, No. 19, pp. 166…
[cited by applicant]
Perez, Edith A., “Paclitaxel in Breast Cancer,”
[cited by applicant]
Petrillo et al., Novel VEGF-independent strategies targeting tumor vasculature: clinical aspects, Current Pharmaceutical Design (2012), 18(19), 2702-2712.
[cited by applicant]
Pettit et al. “Antineoplastic Agents. 291. Isolation and Synthesis of Combretastatins A-4, A-5, and A-6 1a.” J. Med. Chem. (1995) 38: 1666-1672.
[cited by applicant]
Prior et al., “A Comprehensive Survey of Ras Mutations in Cancer”
[cited by applicant]
PRNnewswire.com, Jun. 22, 2010, Nereus Pharmaceuticals completes enrollment of phase 2 advance clinical trial of plinabulin in non-small cell lung cancer, 4 pp.
[cited by applicant]
Rathkopf, Jun. 20, 2008, Phase II trial of docetaxel with rapid androgen cycling for progressive noncastrate prostate cancer, J. Clin. Onc. 26(18):2959-2965.
[cited by applicant]
Raza et al., 2014, Polymorphism: the phenomenon affecting the performance of drugs, SOJ Pharmacy & Pharmaceutical Sciences, 10 pp.
[cited by applicant]
Reck, M., “What future opportunities may immuno-oncology provide for improving the treatment of patients with lung cancer?” (2012) Annals of Oncology (Sep. 2012) 23 (Supp. 8) viii28-viii34.
[cited by applicant]
Remington, “The Science and Practice of Pharmacy, 20th Ed” (2000) p. 709.
[cited by applicant]
Rhodes, John, “Section Review: Biologicals & Immunologicals: Therapeutic potential of Schiff base-forming drugs,” Expert Opinion on Investigational Drugs (1996) vol. 5, Issue 3, pp. 257-268.
[cited by applicant]
Riedel et al., Jun. 2007, A phase II trial of carboplatinvinorelbine with pegfilgrastim support for the treatment of patients with advanced non-small cell lung cancer, Journal of Thoracic Oncology, 2(6):520-525.
[cited by applicant]
Riemer et al., “Matching of trastuzumab (Herceptin®) epitope mimics onto the surface of Her-2/neu—a new method of epitope definition,” Mol Immunol 42 (2005) pp. 1121-1124.
[cited by applicant]
Roberge et al., “Antitumor Drug Fostriecin Inhibits the Mitotic Entry Checkpoint and Protein Phospatases 1 and 2A.” Cancer Res. 54, 6115-21 (1994).
[cited by applicant]
Roberts et al., “Trends in the Risks and Benefits to Patients with Cancer Participating in Phase 12 Clinical Trials”, JAMA (2004) 292(17): 2130-2140.
[cited by applicant]
Rowinsky et al., “The clinical pharmacology and use of antimicrotubule agents in cancer chemotherapeutics”, Pharmacol. Ther. 1991, 52, 35-84.
[cited by applicant]
Rowinsky et al. “Taxol: A Novel Investigational Antimicrotubule Agent.” J. Natl. Cancer Inst. 82(15): 1247-59 (1990).
[cited by applicant]
Rozali et al., “Programmed Death Ligand 2 in Cancer-Induced Immune Suppression,” Clinical and Developmental Immunology (2012) Article ID 656340, pp. 1-8.
[cited by applicant]
Sackett, D.L. “Podophyllotoxin, Steganacin and Combretastatin: Natural Products that Bind at the Colchicine Site of Tubulin.” Pharmacol. Ther. (1993) 59: 163-228.
[cited by applicant]
Saito et al., “Synthesis of novel octahydro-1, 5-imino-3-benzazocin-4, 7, 10-trione derivatives having a methyl group at the C-2 position as ABC ring models of saframycins,” Chemical & Pharmaceutical Bulletin (1997) 45(…
[cited by applicant]
Scholl et al., “Synthetic Lethal Interaction between Oncogenic KRAS Dependency and the STK33 Suppression in Human Cancer Cells”, Cell (May 29, 2009) 137 pp. 821-834.
[cited by applicant]
Selby et al., Sep. 9, 2016, Preclinical development of ipilimumab and nivolumab combination immunotherapy: mouse tumor models, in vitro functional studies, and cynomolgus macaque toxicology, PloS One, 11(9):e0161779, 19…
[cited by applicant]
Sele et al., Jul. 2016, Novel 4-(pyrimidin-2-yl)morpholines targeting the colchicine-binding site of tubuline, Cancer Research, 76(14):abstract 1364.
[cited by applicant]
Sezaki et al., “Drug Delivery Systems”, Drug Development, (Jul. 1989) 13: 116, Table 2. 29.
[cited by applicant]
Shen et al., NPI-2358 rapidly inhibit blood flow in tumor treatment by analyzing dynamic contrast enhanced magnetic resonance imaging parameters, Zhonghua Zhongliu Fangzhi Zazhi (2010), 17(7),488-490, 494.
[cited by applicant]
Shen et al., Time- and dose-dependent vascular changes induced by the novel vascular disrupting drug NPI-2358 in a murine cancer model monitored with DCE-MRI, U.S. Chinese Journal of Lymphology and Oncology(2010), 9(4),…
[cited by applicant]
Sherline et al. “Binding of Colchicine to Purifiied Microtubule Protein.” J. Biol. Chem. 250, 5481-86 (1975).
[cited by applicant]
Shi, Q et al, “Recent progress in the development of tubulin inhibitors as antimitotic antitumor agents”, Curr. Pharm. Des. 1998, 4, 219-248.
[cited by applicant]
Singh et al., “A novel vascular disrupting agent plinabulin triggers JNK-mediated apoptosis and inhibits angiogenesis in multiple myeloma cells,” Blood (2011), 117(21), 5692-5700.
[cited by applicant]
Siwicka et al., “Diastereodivergent Synthesis of 2,5-diketopiperazine Derivatives of Beta-Carboline and Isoquinoline from L-amino Acids,” Tetrahedron: Asymmetry (Mar. 7, 2005) 16(5): 975-993.
[cited by applicant]
Smedsgaard et al. “Using direct electrospray mass spectrometry in taxonomy and secondary metabolite profiling of crude fungal extracts.” J. Microbiol. Meth. (1996) 25: 5-17.
[cited by applicant]
Snegovoy AV, et al. Practical recommendations for the appointment of colony-stimulating factors in order to prevent the development of febrile neuropathy in cancer patients // Practical recommendations. Version 2016. p.…
[cited by applicant]
Sölter et al., Barettin, Revisited? Tetrahed Lttrs. (Mar. 2002) 43: 3385-3386.
[cited by applicant]
Spain et al., Feb. 6, 2016, Management of toxicities of immune checkpoint inhibitors, Cancer Treatment Reviews, 44:51-60.
[cited by applicant]
Spear et al., Vascular disrupting agents (VDA) in oncology: advancing towards new therapeutic paradigms in the clinic, Current Drug Targets (2011), 12(14), 2009-2015.
[cited by applicant]
Stein, J., ed. “Internal Medicine,” Fourth Edition, Mosby-Year Book, Inc., (1994), Chapters 71-72, pp. 699-729.
[cited by applicant]
Stenehjem et al., “PDI/PDLI inhibitors for the treatment of advanced urothelial bladder cancer,” OncoTargets and Therapy (2018) 11:5973-5989.
[cited by applicant]
Steyn, P.S. “The Structures of Five Diketopiperazines from Aspergillus Ustus.” Tetrahedron. 29, 107-120 (1973).
[cited by applicant]
Sugar et al. “Comparison of Three Methods of Antifungal Susceptibility Testing with the Proposed NCCLS Standard Broth Macrodilution Assay: Lack of Effect of Phenol Red.” Diagn Micro and Infect Diseases. 21, 129-133 (199…
[cited by applicant]
Takahashi et al. “Rhizoxin binding to tubulin at the maytansine-binding site.” Biochim. Biophys. Acta. 926, 215-23 (1987).
[cited by applicant]
Talmadge et al., Murine models to evaluate novel and conventional therapeutic strategies for cancer., Am J Pathol, 2007, vol. 170, Issue 3, pp. 793-804.
[cited by applicant]
Thorpe, Philip E., “Vascular Targeting Agents as Cancer Therapeutics,” Clinical Cancer Research, vol. 10, 415-427, Jan. 15, 2004.
[cited by applicant]
Tiwari et al. “A pH- and Temperature-Dependent Cycling Method that doubles the Yield of Microtubule Protein.” Anal. Biochem. 215, 96-103 (1993).
[cited by applicant]
Tonra et al., “Predictive models for tumour cell targeting with plinabulin, derived from in vitro screening and Affymetrix mRNA expression data,” Proc Am Assoc Cancer Res (2019) vol. 60, p. 321, Abstract #1254.
[cited by applicant]
Topalian et al., “Safety, Activity, and Immune Correlates of Anti-PD-1 Antibody in Cancer,” N Engl J Med. (Jun. 28, 2012) 366(26):2443-2454.
[cited by applicant]
Tozer et al., Tumour vascular disrupting agents: combating treatment Resistance, British Journal of Radiology (2008), 81(Spec. Iss. 1), S12-S20.
[cited by applicant]
Turner et al. “Recent Advances in the Medicinal Chemistry of Antifungal Agents.” Current Pharmaceutical Design. 2, 209-224 (1996).
[cited by applicant]
US Food and Drug Administration, Highlights of prescribing information, retrieved Apr. 16, 2020 from https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/125031s180lbl.pdf, Rev. Nov. 2015, Reference ID:4192944.
[cited by applicant]
Usui et al. “Tryprostatin A, a specific and novel inhibitor of microtubule assembly.” Biochem J. 333, 543-48 (1998).
[cited by applicant]
Vainas, 2012, Personalising docetaxel and G-CSF schedules in cancer patients by a clinically validated computational model, British J. Cancer, 107:814-822.
[cited by applicant]
Van der Waerden, B.L., “Wirksamkeits- und Konzentrationsbestimmung durch Tierversuche.” Arch Exp Pathol Pharmakol. 195, 389-412, (1940).
[cited by applicant]
Verdier-Pinard et al., “Structure-Activity Analysis of the Interaction of Curacin A, the Potent Colchicine Site Antimitotic Agent, with Tubulin and Effects of Analogs on the Growth of MCF-7 breast Cancer Cells.” Mol. Ph…
[cited by applicant]
Voskoglou-Nomikos et al., Clinical predictive value of the in vitro cell line, human xenograft, and mouse allograft preclinical cancer models, National Cancer Institute of Canada Clinical Trials Group et al., 2003, vol.…
[cited by applicant]
Wailoo, 2009, The risk of febrile neutropenia in patients with non-small-cell lung cancer treated with docetaxel: a systematic review and meta-analysis, British J. Cancer 100(3):436-441.
[cited by applicant]
Wang, T. et al. 1998 “Microtubule interfering agents activate c-Jun N-terminal kinase/stress-activated protein kinase through both Ras and apoptosis signal-regulating kinase pathways”. J Biol Chem. vol. 273, No. 9, pp. …
[cited by applicant]
Wang, Y. et al., “Structures of a diverse set of colchicine binding site inhibitors in complex with tubulin provide a rationale for drug discovery.” FEBS Journal (2016) 283, 102-111.
[cited by applicant]
Weisenberg et al. “The Colchicine-Binding Protein of Mammalian Brain and its Relation to Microtubules.” Biochemistry (1968) 7(12): 4466-79.
[cited by applicant]
Wilt et al. “Anal cancer in Alaska; a retrospective study of incidence, treatment, and outcomes”. Alaska Med Jul.-Sep. 2002; 44(3):56-9, 62.
[cited by applicant]
Yahara et al. “Microtubule Organization of Lymphocytes and its Modulation by Patch and Cap Formation.” Cell. 15, 251-259 (1978).
[cited by applicant]
Yamato et al., “Clinical importance of B7—H3 expression in human pancreatic cancer,” British Journal of Cancer (Oct. 20, 2009) 101, pp. 1709-1716.
[cited by applicant]