DOCSLIB.ORG

(12) United States Patent (10) Patent No.: US 9,677,055 B2 Jones Et Al

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
(12) United States Patent (10) Patent No.: US 9,677,055 B2 Jones Et Al USOO96770.55B2 (12) United States Patent (10) Patent No.: US 9,677,055 B2 Jones et al. (45) Date of Patent: Jun. 13, 2017 (54) MODIFIED FORMS OF PSEUDOMONAS 2008.0125363 A1 5/2008 Filpula et al. EXOTOXINA 2008/O193976 A1 8, 2008 Harding 2009, O142341 A1 6/2009 Pastan et al. 2009/0305411 A1 12/2009 FitzGerald et al. (71) Applicant: Intrexon Corporation, Blacksburg, VA 2010, 0215656 A1 8, 2010 Pastan et al. (US) 2012/0263674 A1 10, 2012 Pastan et al. (72) Inventors: Timothy David Jones, Cambs (GB); FOREIGN PATENT DOCUMENTS Francis Joseph Carr, Aberdeen (GB) WO WO 88,02401 A1 4f1988 Assignee: Interxon Corporation, Blacksburg, VA WO WO 89.10971 A1 11, 1989 (73) WO WO 90,12592 A1 11, 1990 (US) WO WO 91,09949 A1 7, 1991 WO WO 91,09965 A1 7, 1991 (*) Notice: Subject to any disclaimer, the term of this WO WO 91 18018 A1 11F1991 patent is extended or adjusted under 35 WO WO91f18099 A1 11, 1991 U.S.C. 154(b) by 0 days. WO WO 91.18100 A1 11F1991 WO WO92fO9613 A1 6, 1992 WO WO 93.07.286 A1 4f1993 (21) Appl. No.: 15/234,297 WO WO 93,25690 A1 12, 1993 WO WO 94,04689 A1 3, 1994 (22) Filed: Aug. 11, 2016 WO WO 97,13529 A1 4f1997 WO WO 98/20135 A2 5, 1998 (65) Prior Publication Data WO WO 98/41641 A1 9, 1998 WO WO 99,28471 A2 6, 1999 US 2017/OO37386 A1 Feb. 9, 2017 WO WO O2/40545 A2 5, 2002 WO WO 2004/050849 A2 6, 2004 Related U.S. Application Data (Continued) (63) Continuation of application No. 14/984,006, filed on Dec. 30, 2015, now Pat. No. 9,447,387, which is a OTHER PUBLICATIONS continuation of application No. 14/561,707, filed on Siegall et al., “Cell-Specific Toxicity of a Chimeric Protein Com Dec. 5, 2014, now Pat. No. 9,371,517, which is a posed of Interleukin-6 and Pseudomonas Exotoxin (IL6-PE40) on continuation of application No. 13/604,173, filed on Tumor Cells.” Mol. Cell. Biol., vol. 10, No. 6, pp. 2443-2447, Sep. 5, 2012, now Pat. No. 8,932,586. American Society for Microbiology, Jun. 1990. Pastan et al., “Recombinant Toxins for Cancer Treatment,” Science (60) Provisional application No. 61/531,576, filed on Sep. Mag., vol. 254, pp. 1173-1177, Nov. 22, 1991. Retrieved on Aug. 6, 2011. 29, 2011 from www.sciencemag.org. Siegallet al., “Analysis of Sequences in Domain II of Pseudomonas Exotoxin A Which Mediate Translocation,” Biochem., vol. 30, No. (51) Int. C. 29, pp. 7154-7159. American Chemical Society, 1991. CI2N 9/10 (2006.01) Theuer et al., “Immunotoxins Made with a Recombinant Form of (52) U.S. C. Pseudomonas Exotoxin A That Do Not Require Proteolysis for CPC. CI2N 9/1077 (2013.01); CI2Y 204/02036 Activity.” Cancer Res., vol. 53, pp. 340-347, American Assoc. for Cancer Research, Jan. 15, 1993. Retrieved on Jan. 9, 2014 from (2013.01) www.cancerres.aacjournals.org. (58) Field of Classification Search None (Continued) See application file for complete search history. Primary Examiner — Amber D Steele (56) References Cited Assistant Examiner — Schuyler Milton (74) Attorney, Agent, or Firm — Intrexon Corporation U.S. PATENT DOCUMENTS (57) ABSTRACT 4,545,985 A 10, 1985 Pastan et al. 4,892,827 A 1/1990 Pastan et al. Pseudomonas exotoxin A or “PE is a 66 kD. highly potent, 5,458,878 A 10, 1995 Pastan et al. cytotoxic protein secreted by the bacterium Pseudomonas 5,512,658 A 4, 1996 Pastan et al. 5,602,095 A 2f1997 Pastan et al. aeruginosa. Various forms of PE have been coupled to other 5,696,237 A 12/1997 FitzGerald et al. proteins, such as antibodies, to generate therapeutically 5,705,156 A 1/1998 Pastan et al. useful cytotoxin conjugates that selectively target cells of a 5,705,163 A 1/1998 Pastan et al. desired phenotype (Such as tumor cells). In the present 5,821,238 A 10, 1998 Pastan et al. invention, peptides spanning the sequence of an approxi 5,854,044 A 12/1998 Pastan et al. 5,863,745 A 1/1999 Fitzgerald et al. mately 38 kD form of Pseudomonas exotoxin A protein were 5,980,895 A 11/1999 Pastan et al. analyzed for the presence of immunogenic CD4+ T cell 5,981,726 A 11/1999 Pastan et al. epitopes. Six immunogenic T cell epitopes were identified. 6,051.405 A 4/2000 FitzGerald et al. Residues were identified within each epitope for introduc 6,074,644 A 6, 2000 Pastan et al. 6.426,075 B1 7/2002 Fitzgerald et al. tion of targeted amino acid Substitutions to reduce or prevent 7,314.632 B1 1/2008 Fitzgerald immunogenic T-cell responses in PE molecules which may 7,750,136 B2 7, 2010 Baker et al. be administered to a heterologous host. 8,092,809 B2 1/2012 FitzGerald 2006/0051359 A1 3, 2006 Pastan et al. 23 Claims, 12 Drawing Sheets US 9,677,055 B2 Page 2 (56) References Cited mor Activity in Mice,” J Immunother; vol. 33, No. 3, pp. 297-304. Lippincott Williams & Wilkins, Apr. 2010. Hwang et al., “Functional Domains of Pseudomonas Exotoxin FOREIGN PATENT DOCUMENTS Identified by Deletion Analysis of the Gene Expressed in E. coli,” Cell, vol. 48, pp. 129-136, Cell Press, Jan. 16, 1987. WO WO 2006/065867 A2 6, 2006 Kreitman et al., “Recombinant immunotoxins and other therapies WO WO 2007/O16150 A2 2, 2007 for relapsed/refractory hairy cell leukemia,” Leukemia & Lym WO WO 2009/032954 A1 3, 2009 WO WO 2011/032022 A1 3, 2011 phoma, vol. 52, No. S2, pp. 82-86, Informa UK. Ltd., Jun. 2011. WO WO 2012/154530 A1 11, 2012 Shapira et al., “An Immunoconjugate of Anti-CD24 and WO WO 2012/170617 A1 12/2012 Pseudomonas Exotoxin Selectively Kills Human Colorectal Tumors WO WO 2013/040141 A1 3, 2013 in Mice,” Gastroenterology, vol. 140, No. 3, pp. 935-946, Mar. 2011. Chaudhary et al., “Pseudomonas exotoxin contains a specific OTHER PUBLICATIONS sequence at the carboxyl terminus that is required for cytotoxicity.” Benhar et al., “Pseudomonas Exotoxin A Mutants.” The Journal of Proc. Natl. Acad. Sci. USA, vol. 87, pp. 308-312, Jan. 1990. Biol. Chem., vol. 269, No. 18, pp. 13398-13404, May 6, 1994. Hu et al., “Investigation of a plasmid containing a novel Thomas et al., “Abrogation of Head and Neck Squamous Cell immunotoxin VEGF165-PE38 gene for antiangiogenic therapy in a Carcinoma Growth by Epidermal Growth Factor Receptor Ligand malignant glioma model.” Int. J. Cancer, vol. 127, pp. 2222-2229, Fused to Pseudomonas Exotoxin Transforming Growth Factor 2010. O-PE38.” Clin. Cancer Res., vol. 10, pp. 7079-7087, American Itoi et al., “Targeting of Locus Ceruleus Noradrenergic Neurons Assoc. for Cancer Research, Oct. 15, 2004. Retrieved on Aug. 29. Expressing Human Interleukin-2 Receptor O-Subunit in Transgenic 2012 from www.clincancerres.aacjournals.org. Mice by a Recombinant Immunotoxin anti-Tac(Fv)-PE38: A Study Bang et al., “HA22 (R490A) Is a Recombinant Immunotoxin with for Exploring Noradrenergic Influence upon Anxiety-Like and Increased Antitumor Activity without an Increase in Animal Tox Depression-Like Behaviors.” The Journal of Neuroscience, vol. 31. icity.” Clin. Cancer Res., vol. 11, pp. 1545-1550, American Assoc. No. 16, pp. 6132-6139, Society for Neuroscience, Apr. 20, 2011. for Cancer Research, Feb. 15, 2005. Retrieved on Jan. 9, 2014 from Kuan et al., “Affinity-matured anti-glycoprotein NMB recombinant www.clincancerres.aacjournals.org. immunotoxins targeting malignant gliomas and melanomas,” Ini J Onda et al., “An immunotoxin with greatly reduced immunogenic Cancer; vol. 129, No. 1, pp. 111-121. International Union Against ity by identification and removal of B cell epitopes.” PNAS, vol. Cancer, Jul. 1, 2011. 105, No. 32, pp. 11311-11316. Aug. 12, 2008. Mareeva et al., “A Novel Composite Immunotoxin That Suppresses Weldon et al., “A protease-resistant immunotoxin against CD22 Rabies Virus Production by the Infected Cells,”J Immunol Methods, with greatly increased activity against CLL and diminished animal vol. 353, Nos. 1-2, pp. 1-18, Elsevier B.V., Feb. 28, 2010. toxicity,” Blood, vol. 113, No. 16, pp. 3792-3800, Apr. 16, 2009. Nagata, S. and Pastan, I., “Removal of B cell epitopes as a practical Retrieved on Jan. 9, 2014 from www.bloodjournal. approach for reducing the immunogenicity of foreign protein-based hematologylibrary.org. therapeutics.” Adv. Drug Deliv Rey, vol. 61, No. 11, pp. 977-985, Baker et al., “Pre-Clinical Considerations in the Assessment of Elsevier Science Publishers B.V., Sep. 30, 2009. Immunogenicity for Protein Therapeutics.” Current Drug Safety, Seetharam et al., “Increased Cytotoxic Activity of Pseudomonas vol. 5, No. 4, pp. 1-6, Bentham Science Publishers Ltd., Feb. 19. Exotoxin and Two Chimeric Toxins Ending in KDEL.” The Journal 2010. of Biological Chemistry, vol. 266, No. 26, pp. 17376-17381, Ameri Kreitman et al., “Antibody Fusion Proteins: Anti-CD22 Recombi can Society for Biochemistry and Molecular Biology, Sep. 15, 1991. nant Immunotoxin Moxetumomab Pasudotox,” Clin. Cancer Res., Stish et al., “Design and modification of EGF4KDEL 7Mut, a novel vol. 17, No. 20, pp. 6398-6405, American Assoc. for Cancer bispecific ligand-directed toxin, with decreased immunogenicity Research, Oct. 15, 2011. and potent anti-mesothelioma activity.” British Journal of Cancer, Onda et al., “Recombinant immunotoxin against B-cell malignan vol. 101, Cancer Research UK, Sep. 15, 2009. cies with no immunogenicity in mice by removal of B-cell Theuer et al., “A Recombinant Form of Pseudomonas Exotoxin epitopes.” PNAS, vol.
Load more

Recommended publications
  • Fig. L COMPOSITIONS and METHODS to INHIBIT STEM CELL and PROGENITOR CELL BINDING to LYMPHOID TISSUE and for REGENERATING GERMINAL CENTERS in LYMPHATIC TISSUES
    (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 Χ 23 February 2012 (23.02.2012) WO 2U12/U24519ft ft A2 (51) International Patent Classification: AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, A61K 31/00 (2006.01) CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, (21) International Application Number: HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, PCT/US201 1/048297 KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, (22) International Filing Date: ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, 18 August 201 1 (18.08.201 1) NO, NZ, OM, PE, PG, PH, PL, PT, QA, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, (25) Filing Language: English TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, (26) Publication Language: English ZW. (30) Priority Data: (84) Designated States (unless otherwise indicated, for every 61/374,943 18 August 2010 (18.08.2010) US kind of regional protection available): ARIPO (BW, GH, 61/441,485 10 February 201 1 (10.02.201 1) US GM, KE, LR, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, 61/449,372 4 March 201 1 (04.03.201 1) US ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, (72) Inventor; and EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, ΓΓ, LT, LU, (71) Applicant : DEISHER, Theresa [US/US]; 1420 Fifth LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, Avenue, Seattle, WA 98101 (US).
    [Show full text]
  • Inclusion and Exclusion Criteria for Each Key Question
    Supplemental Table 1: Inclusion and exclusion criteria for each key question Chronic HBV infection in adults ≥ 18 year old (detectable HBsAg in serum for >6 months) Definition of disease Q1 Q2 Q3 Q4 Q5 Q6 Q7 HBV HBV infection with infection and persistent compensated Immunoactive Immunotolerant Seroconverted HBeAg HBV mono-infected viral load cirrhosis with Population chronic HBV chronic HBV from HBeAg to negative population under low level infection infection anti-HBe entecavir or viremia tenofovir (<2000 treatment IU/ml) Adding 2nd Stopped antiviral therapy antiviral drug Interventions and Entecavir compared Antiviral Antiviral therapy compared to continued compared to comparisons to tenofovir therapy therapy continued monotherapy Q1-2: Clinical outcomes: Cirrhosis, decompensated liver disease, HCC and death Intermediate outcomes (if evidence on clinical outcomes is limited or unavailable): HBsAg loss, HBeAg seroconversion and Outcomes HBeAg loss Q3-4: Cirrhosis, decompensated liver disease, HCC, relapse (viral and clinical) and HBsAg loss Q5: Renal function, hypophosphatemia and bone density Q6: Resistance, flare/decompensation and HBeAg loss Q7: Clinical outcomes: Cirrhosis, decompensated liver disease, HCC and death Study design RCT and controlled observational studies Acute HBV infection, children and pregnant women, HIV (+), HCV (+) or HDV (+) persons or other special populations Exclusions such as hemodialysis, transplant, and treatment failure populations. Co treatment with steroids and uncontrolled studies. Supplemental Table 2: Detailed Search Strategy: Ovid Database(s): Embase 1988 to 2014 Week 37, Ovid MEDLINE(R) In-Process & Other Non- Indexed Citations and Ovid MEDLINE(R) 1946 to Present, EBM Reviews - Cochrane Central Register of Controlled Trials August 2014, EBM Reviews - Cochrane Database of Systematic Reviews 2005 to July 2014 Search Strategy: # Searches Results 1 exp Hepatitis B/dt 26410 ("hepatitis B" or "serum hepatitis" or "hippie hepatitis" or "injection hepatitis" or 2 178548 "hepatitis type B").mp.
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 9.468,689 B2 Zeng Et Al
    USOO9468689B2 (12) United States Patent (10) Patent No.: US 9.468,689 B2 Zeng et al. (45) Date of Patent: *Oct. 18, 2016 (54) ULTRAFILTRATION CONCENTRATION OF (56) References Cited ALLOTYPE SELECTED ANTIBODES FOR SMALL-VOLUME ADMINISTRATION U.S. PATENT DOCUMENTS 5,429,746 A 7/1995 Shadle et al. (71) Applicant: Immunomedics, Inc., Morris Plains, NJ 5,789,554 A 8/1998 Leung et al. (US) 6,171,586 B1 1/2001 Lam et al. 6,187,287 B1 2/2001 Leung et al. (72) Inventors: Li Zeng, Edison, NJ (US); Rohini 6,252,055 B1 6/2001 Relton Mitra, Brigdewater, NJ (US); Edmund 6,676,924 B2 1/2004 Hansen et al. 6,870,034 B2 3/2005 Breece et al. A. Rossi, Woodland Park, NJ (US); 6,893,639 B2 5/2005 Levy et al. Hans J. Hansen, Picayune, MS (US); 6,991,790 B1 1/2006 Lam et al. David M. Goldenberg, Mendham, NJ 7,038,017 B2 5, 2006 Rinderknecht et al. (US) 7,074,403 B1 7/2006 Goldenberg et al. 7,109,304 B2 9, 2006 Hansen et al. 7,138,496 B2 11/2006 Hua et al. (73) Assignee: Immunomedics, Inc., Morris Plains, NJ 7,151,164 B2 * 12/2006 Hansen et al. ............. 530,387.3 (US) 7,238,785 B2 7/2007 Govindan et al. 7,251,164 B2 7/2007 Okhonin et al. (*) Notice: Subject to any disclaimer, the term of this 7.282,567 B2 10/2007 Goldenberg et al. patent is extended or adjusted under 35 7,300,655 B2 11/2007 Hansen et al.
    [Show full text]
  • Curriculum Vitae: Daniel J
    CURRICULUM VITAE: DANIEL J. WALLACE, M.D., F.A.C.P., M.A.C.R. Up to date as of January 1, 2019 Personal: Address: 8750 Wilshire Blvd, Suite 350 Beverly Hills, CA 90211 Phone: (310) 652-0010 FAX: (310) 360-6219 E mail: [email protected] Education: University of Southern California, 2/67-6/70, BA Medicine, 1971. University of Southern California, 9/70-6/74, M.D, 1974. Postgraduate Training: 7/74-6/75 Medical Intern, Rhode Island (Brown University) Hospital, Providence, RI. 7/75-6/77 Medical Resident, Cedars-Sinai Medical Center, Los Angeles, CA. 7/77-6/79 Rheumatology Fellow, UCLA School of Medicine, Los Angeles, CA. Medical Boards and Licensure: Diplomate, National Board of Medical Examiners, 1975. Board Certified, American Board of Internal Medicine, 1978. Board Certified, Rheumatology subspecialty, 1982. California License: #G-30533. Present Appointments: Medical Director, Wallace Rheumatic Study Center Attune Health Affiliate, Beverly Hills, CA 90211 Attending Physician, Cedars-Sinai Medical Center, Los Angeles, 1979- Clinical Professor of Medicine, David Geffen School of Medicine at UCLA, 1995- Professor of Medicine, Cedars-Sinai Medical Center, 2012- Expert Reviewer, Medical Board of California, 2007- Associate Director, Rheumatology Fellowship Program, Cedars-Sinai Medical Center, 2010- Board of Governors, Cedars-Sinai Medical Center, 2016- Member, Medical Policy Committee, United Rheumatology, 2017- Honorary Appointments: Fellow, American College of Physicians (FACP) Fellow, American College of Rheumatology (FACR)
    [Show full text]
  • Fontolizumab, a Humanised Anti-Interferon C Antibody
    1131 INFLAMMATORY BOWEL DISEASE Gut: first published as 10.1136/gut.2005.079392 on 28 February 2006. Downloaded from Fontolizumab, a humanised anti-interferon c antibody, demonstrates safety and clinical activity in patients with moderate to severe Crohn’s disease D W Hommes, T L Mikhajlova, S Stoinov, D Sˇtimac, B Vucelic, J Lonovics, M Za´kuciova´, G D’Haens, G Van Assche, S Ba, S Lee, T Pearce ............................................................................................................................... Gut 2006;55:1131–1137. doi: 10.1136/gut.2005.079392 See end of article for Introduction: Interferon c is a potent proinflammatory cytokine implicated in the inflammation of Crohn’s authors’ affiliations ....................... disease (CD). We evaluated the safety and efficacy of fontolizumab, a humanised anti-interferon c antibody, in patients with moderate to severe CD. Correspondence to: Methods: A total of 133 patients with Crohn’s disease activity index (CDAI) scores between 250 and 450, Dr D W Hommes, Department inclusive, were randomised to receive placebo or fontolizumab 4 or 10 mg/kg. Forty two patients Gastroenterology and received one dose and 91 patients received two doses on days 0 and 28. Investigators and patients were Hepatology, Academic unaware of assignment. Study end points were safety, clinical response (decrease in CDAI of 100 points or Medical Centre, C2-111, ( Meibergdreef 9 1105 AZ, more), and remission (CDAI 150). Amsterdam, the Results: There was no statistically significant difference in the primary end point of the study (clinical Netherlands; response) between the fontolizumab and placebo groups after a single dose at day 28. However, patients d.w.hommes@ receiving two doses of fontolizumab demonstrated doubling in response rate at day 56 compared with amc.uva.nl placebo: 32% (9/28) versus 69% (22/32, p = 0.02) and 67% (21/31, p = 0.03) for the placebo, and 4 Revised version received and 10 mg/kg fontolizumab groups, respectively.
    [Show full text]
  • New Biological Therapies: Introduction to the Basis of the Risk of Infection
    New biological therapies: introduction to the basis of the risk of infection Mario FERNÁNDEZ RUIZ, MD, PhD Unit of Infectious Diseases Hospital Universitario “12 de Octubre”, Madrid ESCMIDInstituto de Investigación eLibraryHospital “12 de Octubre” (i+12) © by author Transparency Declaration Over the last 24 months I have received honoraria for talks on behalf of • Astellas Pharma • Gillead Sciences • Roche • Sanofi • Qiagen Infections and biologicals: a real concern? (two-hour symposium): New biological therapies: introduction to the ESCMIDbasis of the risk of infection eLibrary © by author Paul Ehrlich (1854-1915) • “side-chain” theory (1897) • receptor-ligand concept (1900) • “magic bullet” theory • foundation for specific chemotherapy (1906) • Nobel Prize in Physiology and Medicine (1908) (together with Metchnikoff) Infections and biologicals: a real concern? (two-hour symposium): New biological therapies: introduction to the ESCMIDbasis of the risk of infection eLibrary © by author 1981: B-1 antibody (tositumomab) anti-CD20 monoclonal antibody 1997: FDA approval of rituximab for the treatment of relapsed or refractory CD20-positive NHL 2001: FDA approval of imatinib for the treatment of chronic myelogenous leukemia Infections and biologicals: a real concern? (two-hour symposium): New biological therapies: introduction to the ESCMIDbasis of the risk of infection eLibrary © by author Functional classification of targeted (biological) agents • Agents targeting soluble immune effector molecules • Agents targeting cell surface receptors
    [Show full text]
  • WO 2015/028850 Al 5 March 2015 (05.03.2015) P O P C T
    (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 2015/028850 Al 5 March 2015 (05.03.2015) P O P C T (51) International Patent Classification: AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, C07D 519/00 (2006.01) A61P 39/00 (2006.01) BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, C07D 487/04 (2006.01) A61P 35/00 (2006.01) DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, A61K 31/5517 (2006.01) A61P 37/00 (2006.01) HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KN, KP, KR, A61K 47/48 (2006.01) KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, (21) International Application Number: OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, PCT/IB2013/058229 SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, (22) International Filing Date: TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, 2 September 2013 (02.09.2013) ZW. (25) Filing Language: English (84) Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, GH, (26) Publication Language: English GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, SZ, TZ, (71) Applicant: HANGZHOU DAC BIOTECH CO., LTD UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, [US/CN]; Room B2001-B2019, Building 2, No 452 Sixth TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, Street, Hangzhou Economy Development Area, Hangzhou EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, City, Zhejiang 310018 (CN).
    [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]
  • Phage Display-Based Strategies for Cloning and Optimization of Monoclonal Antibodies Directed Against Human Pathogens
    Int. J. Mol. Sci. 2012, 13, 8273-8292; doi:10.3390/ijms13078273 OPEN ACCESS International Journal of Molecular Sciences ISSN 1422-0067 www.mdpi.com/journal/ijms Review Phage Display-based Strategies for Cloning and Optimization of Monoclonal Antibodies Directed against Human Pathogens Nicola Clementi *,†, Nicasio Mancini †, Laura Solforosi, Matteo Castelli, Massimo Clementi and Roberto Burioni Microbiology and Virology Unit, “Vita-Salute” San Raffaele University, Milan 20132, Italy; E-Mails: [email protected] (N.M.); [email protected] (L.S.); [email protected] (M.C.); [email protected] (M.C.); [email protected] (R.B.) † These authors contributed equally to this work. * Author to whom correspondence should be addressed; E-Mail: [email protected]; Tel.: +39-2-2643-5082; Fax: +39-2-2643-4288. Received: 16 March 2012; in revised form: 25 June 2012 / Accepted: 27 June 2012 / Published: 4 July 2012 Abstract: In the last two decades, several phage display-selected monoclonal antibodies (mAbs) have been described in the literature and a few of them have managed to reach the clinics. Among these, the anti-respiratory syncytial virus (RSV) Palivizumab, a phage-display optimized mAb, is the only marketed mAb directed against microbial pathogens. Palivizumab is a clear example of the importance of choosing the most appropriate strategy when selecting or optimizing an anti-infectious mAb. From this perspective, the extreme versatility of phage-display technology makes it a useful tool when setting up different strategies for the selection of mAbs directed against human pathogens, especially when their possible clinical use is considered.
    [Show full text]
  • Promising Therapeutic Targets for Treatment of Rheumatoid Arthritis
    REVIEW published: 09 July 2021 doi: 10.3389/fimmu.2021.686155 Promising Therapeutic Targets for Treatment of Rheumatoid Arthritis † † Jie Huang 1 , Xuekun Fu 1 , Xinxin Chen 1, Zheng Li 1, Yuhong Huang 1 and Chao Liang 1,2* 1 Department of Biology, Southern University of Science and Technology, Shenzhen, China, 2 Institute of Integrated Bioinfomedicine and Translational Science (IBTS), School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China Rheumatoid arthritis (RA) is a systemic poly-articular chronic autoimmune joint disease that mainly damages the hands and feet, which affects 0.5% to 1.0% of the population worldwide. With the sustained development of disease-modifying antirheumatic drugs (DMARDs), significant success has been achieved for preventing and relieving disease activity in RA patients. Unfortunately, some patients still show limited response to DMARDs, which puts forward new requirements for special targets and novel therapies. Understanding the pathogenetic roles of the various molecules in RA could facilitate discovery of potential therapeutic targets and approaches. In this review, both Edited by: existing and emerging targets, including the proteins, small molecular metabolites, and Trine N. Jorgensen, epigenetic regulators related to RA, are discussed, with a focus on the mechanisms that Case Western Reserve University, result in inflammation and the development of new drugs for blocking the various United States modulators in RA. Reviewed by: Åsa Andersson, Keywords: rheumatoid arthritis, targets, proteins, small molecular metabolites, epigenetic regulators Halmstad University, Sweden Abdurrahman Tufan, Gazi University, Turkey *Correspondence: INTRODUCTION Chao Liang [email protected] Rheumatoid arthritis (RA) is classified as a systemic poly-articular chronic autoimmune joint † disease that primarily affects hands and feet.
    [Show full text]
  • Looking for Therapeutic Antibodies in Next Generation Sequencing Repositories
    bioRxiv preprint doi: https://doi.org/10.1101/572958; this version posted March 10, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. Title: Looking for Therapeutic Antibodies in Next Generation Sequencing Repositories. Authors: Konrad Krawczyk1*, Matthew Raybould2, Aleksandr Kovaltsuk2, Charlotte M. Deane2 1 NaturalAntibody, Hamburg, Germany 2 Oxford University Department of Statistics, Oxford, UK *Correspondence to [email protected] Abstract: Recently it has become possible to query the great diversity of natural antibody repertoires using Next Generation Sequencing (NGS). These methods are capable of producing millions of sequences in a single experiment. Here we compare Clinical Stage Therapeutic antibodies to the ~1b sequences from 60 independent sequencing studies in the Observed Antibody Space Database. Of the 242 post Phase I antibodies, we find 16 with sequence identity matches of 95% or better for both heavy and light chains. There are also 54 perfect matches to therapeutic CDR-H3 regions in the NGS outputs, suggesting a nontrivial amount of convergence between naturally observed sequences and those developed artificially. This has potential implications for both the discovery of antibody therapeutics and the legal protection of commercial antibodies. Introduction Antibodies are proteins in jawed vertebrates that recognize noxious molecules (antigens) for elimination. An organism expresses millions of diverse antibodies to increase the chances that some of them will be able to bind the foreign antigen, initiating the adaptive immune response.
    [Show full text]
  • Modifications to the Harmonized Tariff Schedule of the United States To
    U.S. International Trade Commission COMMISSIONERS Shara L. Aranoff, Chairman Daniel R. Pearson, Vice Chairman Deanna Tanner Okun Charlotte R. Lane Irving A. Williamson Dean A. Pinkert Address all communications to Secretary to the Commission United States International Trade Commission Washington, DC 20436 U.S. International Trade Commission Washington, DC 20436 www.usitc.gov Modifications to the Harmonized Tariff Schedule of the United States to Implement the Dominican Republic- Central America-United States Free Trade Agreement With Respect to Costa Rica Publication 4038 December 2008 (This page is intentionally blank) Pursuant to the letter of request from the United States Trade Representative of December 18, 2008, set forth in the Appendix hereto, and pursuant to section 1207(a) of the Omnibus Trade and Competitiveness Act, the Commission is publishing the following modifications to the Harmonized Tariff Schedule of the United States (HTS) to implement the Dominican Republic- Central America-United States Free Trade Agreement, as approved in the Dominican Republic-Central America- United States Free Trade Agreement Implementation Act, with respect to Costa Rica. (This page is intentionally blank) Annex I Effective with respect to goods that are entered, or withdrawn from warehouse for consumption, on or after January 1, 2009, the Harmonized Tariff Schedule of the United States (HTS) is modified as provided herein, with bracketed matter included to assist in the understanding of proclaimed modifications. The following supersedes matter now in the HTS. (1). General note 4 is modified as follows: (a). by deleting from subdivision (a) the following country from the enumeration of independent beneficiary developing countries: Costa Rica (b).
    [Show full text]