DOCSLIB.ORG

(12) Patent Application Publication (10) Pub. No.: US 2014/0228233 A1 Pawlowski Et Al

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
(12) Patent Application Publication (10) Pub. No.: US 2014/0228233 A1 Pawlowski Et Al US 20140228233A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2014/0228233 A1 Pawlowski et al. (43) Pub. Date: Aug. 14, 2014 (54) CIRCULATING BOMARKERS FOR CANCER Publication Classification (76) Inventors: Traci Pawlowski, Laguna Hills, CA (51) Int. Cl. (US); Kimberly Yeatts, Tempe, AZ GOIN33/574 (2006.01) (US); Ray Akhavan, Haymarket, VA CI2O I/68 (2006.01) (US) (52) U.S. Cl. CPC ........ G0IN33/57434 (2013.01): CI2O I/6886 (21) Appl. No.: 14/124.548 (2013.01) USPC .............................. 506/9; 435/7.92; 435/723 (22) PCT Fled: Jun. 7, 2012 (57) ABSTRACT (86) PCT NO.: PCT/US 12/41387 Biomarkers can be assessed for diagnostic, therapy-related or S371 (c)(1), prognostic methods to identify phenotypes, such as a condi (2), (4) Date: Mar. 24, 2014 tion or disease, or the stage or progression of a disease, select candidate treatment regimens for diseases, conditions, dis ease stages, and stages of a condition, and to determine treat Related U.S. Application Data ment efficacy. Circulating biomarkers from a bodily fluid can (60) Provisional application No. 61/494,196, filed on Jun. be used in profiling of physiological states or determining 7, 2011, provisional application No. 61/494,355, filed phenotypes. These include nucleic acids, protein, and circu on Jun. 7, 2011, provisional application No. 61/507, lating structures Such as vesicles, and nucleic acid-protein 989, filed on Jul. 14, 2011. complexes. Patent Application Publication US 2014/0228233 A1 ?oueoseuon]-, ?oueoseuon]-, ?oueoseuon]-, Patent Application Publication Aug. 14, 2014 Sheet 3 of 22 US 2014/0228233 A1 ?oueoseuon]-, ?oueoseuon]-, ?oueoseuon]-, Patent Application Publication Aug. 14, 2014 Sheet 4 of 22 US 2014/0228233 A1 Patent Application Publication Aug. 14, 2014 Sheet 5 of 22 US 2014/0228233 A1 Z099 |||99 ?un?deO Patent Application Publication Aug. 14, 2014 Sheet 6 of 22 US 2014/0228233 A1 Z999|9990999 ZZ99 Patent Application Publication Aug. 14, 2014 Sheet 7 of 22 US 2014/0228233 A1 s (Y) () iu/ S : Patent Application Publication Aug. 14, 2014 Sheet 9 of 22 US 2014/0228233 A1 pe08=peægqZ96|peagWWOdE |n/6u00g 00,6Z 00°99 O Patent Application Publication Aug. 14, 2014 Sheet 10 of 22 US 2014/0228233 A1 miR21 Expression with CD-9 Bead Capture oEead Captured supernatant SE . 3. E. :au?e Elseratant Patent Application Publication Aug. 14, 2014 Sheet 11 of 22 US 2014/0228233 A1 swax. sws: & Patent Application Publication Aug. 14, 2014 Sheet 12 of 22 US 2014/0228233 A1 & SS uds N S ¿n?a.SS SS N. S ae ŠašŠ ()euuseid?••~----- ! Patent Application Publication Aug. 14, 2014 Sheet 13 of 22 US 2014/0228233 A1 s s &x. XXXX-XXX-XXXX-XXXX-XXXX-XXX-XXX-X 8. Patent Application Publication Aug. 14, 2014 Sheet 14 of 22 Patent Application Publication Aug. 14, 2014 Sheet 16 of 22 US 2014/0228233 A1 SYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYY-SYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYY Patent Application Publication Aug. 14, 2014 Sheet 17 of 22 US 2014/0228233 A1 VSOdpeÐH HI«pis-lawX. HL<HWNX ?Idues ÎHI>IHWX Patent Application Publication Aug. 14, 2014 Sheet 18 of 22 US 2014/0228233 A1 g 3H H. e CC O h CD .9 V CD D S AIAI)SueS Patent Application Publication Aug. 14, 2014 Sheet 19 of 22 US 2014/0228233 A1 Patent Application Publication Aug. 14, 2014 Sheet 20 of 22 US 2014/0228233 A1 Vesicle Test Negatives Converting false negatives to true positives improves sensitivity True Negatives False Negatives Use payload to identify true positives False True Negatives Positives Vesicle Test Positives Converting false positives to true negatives improves specificity False True Positives Positives Use payload to identify true positives True False Negatives Positives • Mishandled samples • Undiagnosed disease • Confounding disease FIG. 13A-B Patent Application Publication Aug. 14, 2014 Sheet 21 of 22 US 2014/0228233 A1 tio Z. Patent Application Publication Aug. 14, 2014 Sheet 22 of 22 US 2014/0228233 A1 3. e e s k s c s s y N star & LeoS8.30 GSS Ae e3e3Selo QSS Ae 8. L & O e C s * V • V g CX D O CD 5 s . * ?a %, L k s 3380Saoli nSS 8Ae- 33480Seol (SSS We s * &% reas wes - g5 ic % & eu83Sejol (SSg. We 308) Sejo (SSg Aes US 2014/0228233 A1 Aug. 14, 2014 CIRCULATING BOMARKERS FOR CANCER 0007. The identification of specific biomarkers, such as DNA, RNA and proteins, can provide biosignatures that are CROSS REFERENCE used for the diagnosis, prognosis, or theranosis of conditions 0001. This application claims the benefit of U.S. Provi or diseases. Biomarkers can be detected in bodily fluids, sional Patent Application Nos. 61/494,196, filed Jun. 7, 2011; including circulating DNA, RNA, proteins, and vesicles. Cir 61/494,355, filed Jun. 7, 2011; and 61/507,989, filed Jul. 14, culating biomarkers include proteins such as PSA and 2011; all of which applications are incorporated herein by CA125, and nucleic acids such as SEPT9 DNA and PCA3 reference in their entirety. messenger RNA (mRNA). Circulating biomarkers can be 0002 This application is a continuation-in-part of Inter associated with circulating vesicles. Vesicles are membrane national Patent Application PCT/US2012/025741, filed Feb. encapsulated structures that are shed from cells and have been 17, 2012, which application claims the benefit of U.S. Provi found in a number of bodily fluids, including blood, plasma, sional Patent Application Nos. 61/446.313, filed Feb. 24. serum, breast milk, ascites, bronchoalveolar lavage fluid and 2011: 61/501,680, filed Jun. 27, 2011: 61/471,417, filed Apr. urine. Vesicles can take part in the communication between 4, 2011: 61/523,763, filed Aug. 15, 2011; and 61/445,273, cells as transport vehicles for proteins, RNAs, DNAs, viruses, filed Feb. 22, 2011; all of which applications are incorporated and prions. MicroRNAs are short RNAs that regulate the herein by reference in their entirety. transcription and degradation of messenger RNAS. MicroR 0003. This application is also a continuation-in-part of NAs have been found in bodily fluids and have been observed International Patent Application PCT/US2011/048327, filed as a component within vesicles shed from tumor cells. The Aug. 18, 2011, which application claims the benefit of U.S. analysis of circulating biomarkers associated with diseases, Provisional Patent Application Nos. 61/374,951, filed Aug. including vesicles and/or microRNA, can aid in detection of 18, 2010: 61/379,670, filed Sep. 2, 2010: 61/381,305, filed disease or severity thereof, determining predisposition to a Sep. 9, 2010: 61/383,305, filed Sep. 15, 2010: 61/391,504, disease, as well as making treatment decisions. filed Oct. 8, 2010: 61/393,823, filed Oct. 15, 2010: 61/411, 0008 Vesicles present in a biological sample provide a 890, filed Nov. 9, 2010: 61/414,870, filed Nov. 17, 2010; Source of biomarkers, e.g., the markers are present within a 61/416,560, filed Nov. 23, 2010: 61/421,851, filed Dec. 10, vesicle (vesicle payload), or are present on the Surface of a 2010: 61/423,557, filed Dec. 15, 2010: 61/428,196, filed Dec. vesicle. Characteristics of vesicles (e.g., size, Surface anti 29, 2010; all of which applications are incorporated herein by gens, determination of cell-of-origin, payload) can also pro reference in their entirety. vide a diagnostic, prognostic or theranostic readout. There 0004. This application is also a continuation-in-part of remains a need to identify biomarkers that can be used to International Patent Application PCT/US2011/026750, filed detect and treat disease. microRNA, proteins and other biom Mar. 1, 2011, which application claims is a continuation-in arkers associated with vesicles as well as the characteristics of part application of U.S. patent application Ser. No. 12/591, a vesicle can provide a diagnosis, prognosis, or theranosis. 226, filed Nov. 12, 2009, which claims the benefit of U.S. 0009. The present invention provides methods and sys Provisional Application Nos. 61/114,045, filed Nov. 12, tems for characterizing a phenotype by detecting biomarkers 2008: 61/114,058, filed Nov. 12, 2008: 61/114,065, filed Nov. that are indicative of disease or disease progress. The biom 13, 2008: 61/151,183, filed Feb. 9, 2009: 61/278,049, filed arkers can be circulating biomarkers including without limi Oct. 2, 2009: 61/250,454, filed Oct. 9, 2009; and 61/253,027 tation vesicle markers, protein, nucleic acids, mRNA, or filed Oct. 19, 2009; and which application also claims the microRNA. The biomarkers can be nucleic acid-protein com benefit of U.S. Provisional Application Nos. 61/274,124. plexes. filed Mar. 1, 2010: 61/357,517, filed Jun. 22, 2010: 61/364, 785, filed Jul. 15, 2010; all of which applications are incor SUMMARY porated herein by reference in their entirety. 0010 Disclosed herein are methods and compositions for 0005. This application is also a continuation-in-part of characterizing a phenotype by analyzing circulating biomar International Patent Application PCT/US2011/031479, filed kers, such as a vesicle, microRNA or protein present in a Apr. 6, 2011, which application claims the benefit of U.S. biological sample. Characterizing a phenotype for a subject Provisional Patent Application Nos. 61/321,392, filed Apr. 6, or individual may include, but is not limited to, the diagnosis 2010: 61/321,407, filed Apr. 6, 2010: 61/332,174, filed May of a disease or condition, the prognosis of a disease or con 6, 2010: 61/348,214, filed May 25, 2010, 61/348,685, filed dition, the determination of a disease stage or a condition May 26, 2010: 61/354,125, filed Jun.
Load more

Recommended publications
  • HER2 Inhibition in Gastro-Oesophageal Cancer: a Review Drawing on Lessons Learned from Breast Cancer
    Submit a Manuscript: http://www.f6publishing.com World J Gastrointest Oncol 2018 July 15; 10(7): 159-171 DOI: 10.4251/wjgo.v10.i7.159 ISSN 1948-5204 (online) REVIEW HER2 inhibition in gastro-oesophageal cancer: A review drawing on lessons learned from breast cancer Hazel Lote, Nicola Valeri, Ian Chau Hazel Lote, Nicola Valeri, Centre for Molecular Pathology, Accepted: May 30, 2018 Institute of Cancer Research, Sutton SM2 5NG, United Kingdom Article in press: May 30, 2018 Published online: July 15, 2018 Hazel Lote, Nicola Valeri, Ian Chau, Department of Medicine, Royal Marsden Hospital, Sutton SM2 5PT, United Kingdom ORCID number: Hazel Lote (0000-0003-1172-0372); Nicola Valeri (0000-0002-5426-5683); Ian Chau (0000-0003-0286-8703). Abstract Human epidermal growth factor receptor 2 (HER2)- Author contributions: Lote H wrote the original manuscript and revised it following peer review comments; Valeri N reviewed inhibition is an important therapeutic strategy in HER2- the manuscript; Chau I reviewed and contributed to the content of amplified gastro-oesophageal cancer (GOC). A significant the manuscript. proportion of GOC patients display HER2 amplification, yet HER2 inhibition in these patients has not displayed Supported by National Health Service funding to the National the success seen in HER2 amplified breast cancer. Mu- Institute for Health Research Biomedical Research Centre at ch of the current evidence surrounding HER2 has been the Royal Marsden NHS Foundation Trust and The Institute of obtained from studies in breast cancer, and we are only re- Cancer Research, No. A62, No. A100, No. A101 and No. A159; Cancer Research UK funding, No.
    [Show full text]
  • WO 2018/223101 Al 06 December 2018 (06.12.2018) W !P O PCT
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2018/223101 Al 06 December 2018 (06.12.2018) W !P O PCT (51) International Patent Classification: (71) Applicant: JUNO THERAPEUTICS, INC. [US/US]; 400 A 61K 35/1 7 (20 15.0 1) A 61P 35/00 (2006 .0 1) Dexter Ave. N., Suite 1200, Seattle, WA 98109 (US). (21) International Application Number: (72) Inventor: ALBERTSON, Tina; 400 Dexter Ave. N., Suite PCT/US2018/035755 1200, Seattle, WA 98109 (US). (22) International Filing Date: (74) Agent: AHN, Sejin et al; Morrison & Foerster LLP, 1253 1 0 1 June 2018 (01 .06.2018) High Bluff Drive, Suite 100, San Diego, CA 92130-2040 (US). (25) Filing Language: English (81) Designated States (unless otherwise indicated, for every (26) Publication Language: English kind of national protection available): AE, AG, AL, AM, (30) Priority Data: AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, 62/5 14,774 02 June 2017 (02.06.2017) US CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, 62/5 15,530 05 June 2017 (05.06.2017) US DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, 62/521,366 16 June 2017 (16.06.2017) u s HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, 62/527,000 29 June 2017 (29.06.2017) u s KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, 62/549,938 24 August 2017 (24.08.2017) u s MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, 62/580,425 0 1 November 2017 (01 .11.2017) u s OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, 62/593,871 0 1 December 2017 (01 .12.2017) u s SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, 62/596,764 08 December 2017 (08.12.2017) u s TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW.
    [Show full text]
  • Or Ramucirumab (IMC-1121B) Plus Mitoxantrone and Prednisone in Men with Metastatic Docetaxel-Pretreated Castration-Resistant Prostate Cancer
    European Journal of Cancer (2015) 51, 1714– 1724 Available at www.sciencedirect.com ScienceDirect journal homepage: www.ejcancer.com A randomised non-comparative phase II trial of cixutumumab (IMC-A12) or ramucirumab (IMC-1121B) plus mitoxantrone and prednisone in men with metastatic docetaxel-pretreated castration-resistant prostate cancer Maha Hussain a,1,⇑, Dana Rathkopf b,1, Glenn Liu c,1, Andrew Armstrong d,1, Wm. Kevin Kelly e, Anna Ferrari f, John Hainsworth g, Adarsh Joshi h, Rebecca R. Hozak i, Ling Yang h, Jonathan D. Schwartz h,2, Celestia S. Higano j,1 a University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, United States b Memorial Sloan-Kettering, New York, NY, United States c University of Wisconsin, Carbone Cancer Center, Madison, WI, United States d Duke Cancer Institute and Duke Prostate Center, Duke University, Durham, NC, United States e Thomas Jefferson University, Philadelphia, PA, United States f New York University Clinical Cancer Center, New York, NY, United States g Sarah Cannon Research Institute, Nashville, TN, United States h Eli Lilly and Company, Bridgewater, NJ, United States i Eli Lilly and Company, Indianapolis, IN, United States j University of Washington, Fred Hutchinson Cancer Research Center, Seattle, WA, United States Received 11 February 2015; received in revised form 27 April 2015; accepted 10 May 2015 Available online 13 June 2015 KEYWORDS Abstract Background: Cixutumumab, a human monoclonal antibody (HuMAb), targets the Ramucirumab insulin-like growth factor receptor. Ramucirumab is a recombinant HuMAb that binds to vas- Cixutumumab cular endothelial growth factor receptor-2. A non-comparative randomised phase II study Mitoxantrone evaluated cixutumumab or ramucirumab plus mitoxantrone and prednisone (MP) in Prednisone metastatic castration-resistant prostate cancer (mCRPC).
    [Show full text]
  • Tanibirumab (CUI C3490677) Add to Cart
    5/17/2018 NCI Metathesaurus Contains Exact Match Begins With Name Code Property Relationship Source ALL Advanced Search NCIm Version: 201706 Version 2.8 (using LexEVS 6.5) Home | NCIt Hierarchy | Sources | Help Suggest changes to this concept Tanibirumab (CUI C3490677) Add to Cart Table of Contents Terms & Properties Synonym Details Relationships By Source Terms & Properties Concept Unique Identifier (CUI): C3490677 NCI Thesaurus Code: C102877 (see NCI Thesaurus info) Semantic Type: Immunologic Factor Semantic Type: Amino Acid, Peptide, or Protein Semantic Type: Pharmacologic Substance NCIt Definition: A fully human monoclonal antibody targeting the vascular endothelial growth factor receptor 2 (VEGFR2), with potential antiangiogenic activity. Upon administration, tanibirumab specifically binds to VEGFR2, thereby preventing the binding of its ligand VEGF. This may result in the inhibition of tumor angiogenesis and a decrease in tumor nutrient supply. VEGFR2 is a pro-angiogenic growth factor receptor tyrosine kinase expressed by endothelial cells, while VEGF is overexpressed in many tumors and is correlated to tumor progression. PDQ Definition: A fully human monoclonal antibody targeting the vascular endothelial growth factor receptor 2 (VEGFR2), with potential antiangiogenic activity. Upon administration, tanibirumab specifically binds to VEGFR2, thereby preventing the binding of its ligand VEGF. This may result in the inhibition of tumor angiogenesis and a decrease in tumor nutrient supply. VEGFR2 is a pro-angiogenic growth factor receptor
    [Show full text]
  • Therapeutic Targeting of the IGF Axis
    cells Review Therapeutic Targeting of the IGF Axis Eliot Osher and Valentine M. Macaulay * Department of Oncology, University of Oxford, Oxford, OX3 7DQ, UK * Correspondence: [email protected]; Tel.: +44-1865617337 Received: 8 July 2019; Accepted: 9 August 2019; Published: 14 August 2019 Abstract: The insulin like growth factor (IGF) axis plays a fundamental role in normal growth and development, and when deregulated makes an important contribution to disease. Here, we review the functions mediated by ligand-induced IGF axis activation, and discuss the evidence for the involvement of IGF signaling in the pathogenesis of cancer, endocrine disorders including acromegaly, diabetes and thyroid eye disease, skin diseases such as acne and psoriasis, and the frailty that accompanies aging. We discuss the use of IGF axis inhibitors, focusing on the different approaches that have been taken to develop effective and tolerable ways to block this important signaling pathway. We outline the advantages and disadvantages of each approach, and discuss progress in evaluating these agents, including factors that contributed to the failure of many of these novel therapeutics in early phase cancer trials. Finally, we summarize grounds for cautious optimism for ongoing and future studies of IGF blockade in cancer and non-malignant disorders including thyroid eye disease and aging. Keywords: IGF; type 1 IGF receptor; IGF-1R; cancer; acromegaly; ophthalmopathy; IGF inhibitor 1. Introduction Insulin like growth factors (IGFs) are small (~7.5 kDa) ligands that play a critical role in many biological processes including proliferation and protection from apoptosis and normal somatic growth and development [1]. IGFs are members of a ligand family that includes insulin, a dipeptide comprised of A and B chains linked via two disulfide bonds, with a third disulfide linkage within the A chain.
    [Show full text]
  • Stems for Nonproprietary Drug Names
    USAN STEM LIST STEM DEFINITION EXAMPLES -abine (see -arabine, -citabine) -ac anti-inflammatory agents (acetic acid derivatives) bromfenac dexpemedolac -acetam (see -racetam) -adol or analgesics (mixed opiate receptor agonists/ tazadolene -adol- antagonists) spiradolene levonantradol -adox antibacterials (quinoline dioxide derivatives) carbadox -afenone antiarrhythmics (propafenone derivatives) alprafenone diprafenonex -afil PDE5 inhibitors tadalafil -aj- antiarrhythmics (ajmaline derivatives) lorajmine -aldrate antacid aluminum salts magaldrate -algron alpha1 - and alpha2 - adrenoreceptor agonists dabuzalgron -alol combined alpha and beta blockers labetalol medroxalol -amidis antimyloidotics tafamidis -amivir (see -vir) -ampa ionotropic non-NMDA glutamate receptors (AMPA and/or KA receptors) subgroup: -ampanel antagonists becampanel -ampator modulators forampator -anib angiogenesis inhibitors pegaptanib cediranib 1 subgroup: -siranib siRNA bevasiranib -andr- androgens nandrolone -anserin serotonin 5-HT2 receptor antagonists altanserin tropanserin adatanserin -antel anthelmintics (undefined group) carbantel subgroup: -quantel 2-deoxoparaherquamide A derivatives derquantel -antrone antineoplastics; anthraquinone derivatives pixantrone -apsel P-selectin antagonists torapsel -arabine antineoplastics (arabinofuranosyl derivatives) fazarabine fludarabine aril-, -aril, -aril- antiviral (arildone derivatives) pleconaril arildone fosarilate -arit antirheumatics (lobenzarit type) lobenzarit clobuzarit -arol anticoagulants (dicumarol type) dicumarol
    [Show full text]
  • Primary and Acquired Resistance to Immunotherapy in Lung Cancer: Unveiling the Mechanisms Underlying of Immune Checkpoint Blockade Therapy
    cancers Review Primary and Acquired Resistance to Immunotherapy in Lung Cancer: Unveiling the Mechanisms Underlying of Immune Checkpoint Blockade Therapy Laura Boyero 1 , Amparo Sánchez-Gastaldo 2, Miriam Alonso 2, 1 1,2,3, , 1,2, , José Francisco Noguera-Uclés , Sonia Molina-Pinelo * y and Reyes Bernabé-Caro * y 1 Institute of Biomedicine of Seville (IBiS) (HUVR, CSIC, Universidad de Sevilla), 41013 Seville, Spain; [email protected] (L.B.); [email protected] (J.F.N.-U.) 2 Medical Oncology Department, Hospital Universitario Virgen del Rocio, 41013 Seville, Spain; [email protected] (A.S.-G.); [email protected] (M.A.) 3 Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), 28029 Madrid, Spain * Correspondence: [email protected] (S.M.-P.); [email protected] (R.B.-C.) These authors contributed equally to this work. y Received: 16 November 2020; Accepted: 9 December 2020; Published: 11 December 2020 Simple Summary: Immuno-oncology has redefined the treatment of lung cancer, with the ultimate goal being the reactivation of the anti-tumor immune response. This has led to the development of several therapeutic strategies focused in this direction. However, a high percentage of lung cancer patients do not respond to these therapies or their responses are transient. Here, we summarized the impact of immunotherapy on lung cancer patients in the latest clinical trials conducted on this disease. As well as the mechanisms of primary and acquired resistance to immunotherapy in this disease. Abstract: After several decades without maintained responses or long-term survival of patients with lung cancer, novel therapies have emerged as a hopeful milestone in this research field.
    [Show full text]
  • Eisai Submits Marketing Authorization Application in Japan
    N o. 20-15 March 26, 2020 Eisai Co., Ltd. EISAI SUBMITS MARKETING AUTHORIZATION APPLICATION IN JAPAN FOR ANTICANCER AGENT DENILEUKIN DIFTITOX (GENETIC RECOMBINANT) FOR CUTANEOUS T-CELL LYMPHOMA AND PERIPHERAL T-CELL LYMPHOMA Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”) announced today that it has submitted in Japan a marketing authorization application of the anticancer agent denileukin diftitox (genetic recombinant) (generic name, development code: E7777) for relapsed or refractory Cutaneous T-cell Lymphoma (CTCL) and Peripheral T-cell Lymphoma (PTCL). This application is based on data from a multicenter, open-label, single-arm Phase II clinical study (study 205) conducted in Japan for patients with relapsed or refractory CTCL or PTCL to evaluate the efficacy and safety of this agent. This study achieved the primary endpoint and exceeded a predetermined threshold with statistical significance: the objective response rate (ORR) of CTCL and PTCL patients in total (n=36) was 36.1% (95% confidence interval (CI): 20.8-53.8). The ORRs of each subtype were 31.6% (95% CI：12.6-56.6) for CTCL (n=19) and 41.2% (95%CI: 18.4-67.1) for PTCL (n=17). The five most frequent adverse events observed in this study were increased aspartate aminotransferase (AST) (89.2%), increased alanine aminotransferase (ALT) (86.5%), hypoalbuminaemia (70.3%), lymphopenia (70.3%), and pyrexia (51.4%). Denileukin diftitox (genetic recombinant) is a fusion protein of the receptor-binding portion of interleukin-2 (IL-2) and diphtheria toxin that specifically binds to the IL-2 receptor on the surface of tumoral lymphocyte.
    [Show full text]
  • A Bispecific Enediyne-Energized Fusion Protein Targeting Both Epidermal Growth Factor Receptor and Insulin-Like Growth Factor 1
    www.impactjournals.com/oncotarget/ Oncotarget, 2017, Vol. 8, (No. 16), pp: 27286-27299 Research Paper A bispecific enediyne-energized fusion protein targeting both epidermal growth factor receptor and insulin-like growth factor 1 receptor showing enhanced antitumor efficacy against non- small cell lung cancer Xiao-Fang Guo1, Xiao-Fei Zhu2,3, Hai-Ying Cao1, Gen-Shen Zhong4, Liang Li5, Bao-Guo Deng1, Ping Chen1, Pei-Zhen Wang1, Qing-Fang Miao5, Yong-Su Zhen5 1Department of Microbiology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, China 2Department of Clinical Immunology, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, China 3Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, Xinxiang, China 4Laboratory of Cancer Biotherapy, Institute of Neurology, The First Affiliated Hospital of Xinxiang Medical University, Weihui, China 5Department of Oncology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Perking Union Medical College, Beijing, China Correspondence to: Xiao-Fang Guo, email: [email protected] Yong-Su Zhen, email: [email protected] Keywords: EGFR, IGF-1R, lidamycin, bispecific fusion protein, NSCLC Received: July 04, 2016 Accepted: February 20, 2017 Published: March 06, 2017 Copyright: Guo et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC-BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited ABSTRACT Epidermal growth factor receptor (EGFR) and insulin-like growth factor 1 receptor (IGF-1R) both overexpressed on non-small cell lung cancer (NSCLC) and are known cooperatively to promote tumor progression and drug resistance. This study was to construct a novel bispecific fusion protein EGF-IGF-LDP-AE consisting of EGFR and IGF-IR specific ligands (EGF and IGF-1) and lidamycin, an enediyne antibiotic with potent antitumor activity, and investigate its antitumor efficacy against NSCLC.
    [Show full text]
  • A Randomized, Open-Label, Phase 3 Trial of Brentuximab Vedotin
    Title: A Randomized, Open-Label, Phase 3 Trial of brentuximab vedotin (SGN-35) Versus Physician's Choice (Methotrexate or Bexarotene) in Patients With CD30-Positive Cutaneous T- Cell Lymphoma NCT Number: NCT01578499 Protocol Approve Date: 02 December 2014 Certain information within this protocol has been redacted (ie, specific content is masked irreversibly from view with a black/blue bar) to protect either personally identifiable information (PPD) or company confidential information (CCI). This may include, but is not limited to, redaction of the following: Named persons or organizations associated with the study. Proprietary information, such as scales or coding systems, which are considered confidential information under prior agreements with license holder. • Other information as needed to protect confidentiality of Takeda or partners, personal information, or to otherwise protect the integrity of the clinical study. Brentuximab vedotin (SGN-35) Clinical Study Protocol C25001 Amendment 5, EudraCT: 2010-024215-14 CLINICAL STUDY PROTOCOL C25001 AMENDMENT 5 Brentuximab vedotin (SGN-35) A Randomized, Open-Label, Phase 3 Trial of brentuximab vedotin (SGN-35) Versus Physician's Choice (Methotrexate or Bexarotene) in Patients With CD30-Positive Cutaneous T-Cell Lymphoma Protocol Number: C25001 Indication: CD30 Positive Cutaneous T-Cell Lymphoma Phase: 3 Sponsor: Millennium Pharmaceuticals, Inc. EudraCT Number: 2010-024215-14 Therapeutic Area: Oncology Protocol History Original 11 July 2011 Amendment 1 21 December 2011 Amendment 2 24 February 2012 Amendment 3 04 March 2013 Amendment 4 03 July 2013 Amendment 5 02 December 2014 Millennium Pharmaceuticals, Inc. 40 Landsdowne Street Cambridge, MA USA 02139 Telephone: +1 (617) 679-7000 Approved by: Note: If this document was approved electronically, the electronic approval signatures may be found at the end of the document.
    [Show full text]
  • Role of Denileukin Diftitox in the Treatment of Persistent Or Recurrent Cutaneous T-Cell Lymphoma
    Cancer Management and Research Dovepress open access to scientific and medical research Open Access Full Text Article R EVIEW Role of denileukin diftitox in the treatment of persistent or recurrent cutaneous T-cell lymphoma Frederick Lansigan1 Abstract: Denileukin diftitox (Ontak®) is indicated for the treatment of patients with persistent Diane M Stearns1 or recurrent cutaneous T-cell lymphoma (CTCL), a rare lymphoproliferative disorder of the Francine Foss2 skin. Denileukin diftitox was the first fusion protein toxin approved for the treatment of a human disease. This fusion protein toxin combines the IL2 protein with diphtheria toxin, and targets the 1Hematology/Oncology, Norris Cotton Cancer Center, Dartmouth CD25 subunit of the IL2 receptor, resulting in the unique delivery of a cytocidal agent to CD-25 Hitchcock Medical Center, Lebanon, bearing T-cells. Historically, immunotherapy targeting malignant T-cells including monoclonal 2 NH, USA; Yale Comprehensive antibodies has been largely ineffective as cytocidal agents compared to immunotherapy directed Cancer Center, Yale University School of Medicine, New Haven, CT, USA against B-cells such as rituximab. This review will summarize the development of denileukin diftitox, its proposed mechanism of action, the pivotal clinical trials that led to its FDA approval, For personal use only. the improvements in quality of life, and the common toxicities experienced during the treatment of patients with CTCL. CTCL is often a chronic progressive lymphoma requiring the sequential use of treatments
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2009/0005722 A1 Jennings-Spring (43) Pub
    US 20090005722A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2009/0005722 A1 Jennings-Spring (43) Pub. Date: Jan. 1, 2009 (54) SKIN-CONTACTING-ADHESIVE FREE Publication Classification DRESSING (51) Int. Cl. Inventor: Barbara Jennings-Spring, Jupiter, A61N L/30 (2006.01) (76) A6F I3/00 (2006.01) FL (US) A6IL I5/00 (2006.01) Correspondence Address: AOIG 7/06 (2006.01) Irving M. Fishman AOIG 7/04 (2006.01) c/o Cohen, Tauber, Spievack and Wagner (52) U.S. Cl. .................. 604/20: 602/43: 602/48; 4771.5; Suite 2400, 420 Lexington Avenue 47/13 New York, NY 10170 (US) (57) ABSTRACT (21) Appl. No.: 12/231,104 A dressing having a flexible sleeve shaped to accommodate a Substantially cylindrical body portion, the sleeve having a (22) Filed: Aug. 29, 2008 lining which is substantially non-adherent to the body part being bandaged and having a peripheral securement means Related U.S. Application Data which attaches two peripheral portions to each other without (63) Continuation-in-part of application No. 1 1/434,689, those portions being circumferentially adhered to the sleeve filed on May 16, 2006. portion. Patent Application Publication Jan. 1, 2009 Sheet 1 of 9 US 2009/0005722 A1 Patent Application Publication Jan. 1, 2009 Sheet 2 of 9 US 2009/0005722 A1 10 8 F.G. 5 Patent Application Publication Jan. 1, 2009 Sheet 3 of 9 US 2009/0005722 A1 13 FIG.6 2 - Y TIII Till "T fift 11 10 FIG.7 8 13 6 - 12 - Timir" "in "in "MINIII.
    [Show full text]