| EP3303400 - CELL-BASED ASSAY FOR DETECTING ANTI-CD3 HOMODIMERS [Right-click to bookmark this link] | Status | No opposition filed within time limit Status updated on 16.07.2021 Database last updated on 09.04.2026 | |
| Former | The patent has been granted Status updated on 07.08.2020 | ||
| Former | Grant of patent is intended Status updated on 29.03.2020 | ||
| Former | Examination is in progress Status updated on 25.01.2019 | ||
| Former | Request for examination was made Status updated on 09.03.2018 | ||
| Former | The international publication has been made Status updated on 02.12.2016 | Most recent event Tooltip | 13.09.2024 | Lapse of the patent in a contracting state New state(s): MT | published on 16.10.2024 [2024/42] | Applicant(s) | For all designated states Genentech, Inc. 1 DNA Way South San Francisco, CA 94080-4990 / US | [2018/15] | Inventor(s) | 01 /
CAREY, Kendall 545 Miller Avenue, Apt. No.5 South San Francisco, CA 94080 / US | [2020/37] |
| Former [2018/15] | 01 /
CAREY, Kendall c/o Genentech, Inc. 1 DNA Way South San Francisco, CA 94080-4990 / US | Representative(s) | Mewburn Ellis LLP Aurora Building Counterslip Bristol BS1 6BX / GB | [2020/37] |
| Former [2018/15] | Denison, Christopher Marcus Mewburn Ellis LLP City Tower 40 Basinghall Street London EC2V 5DE / GB | Application number, filing date | 16732377.3 | 27.05.2016 | [2018/15] | WO2016US34868 | Priority number, date | US201562167761P | 28.05.2015 Original published format: US 201562167761 P | [2018/15] | Filing language | EN | Procedural language | EN | Publication | Type: | A1 Application with search report | No.: | WO2016191750 | Date: | 01.12.2016 | Language: | EN | [2016/48] | Type: | A1 Application with search report | No.: | EP3303400 | Date: | 11.04.2018 | Language: | EN | The application published by WIPO in one of the EPO official languages on 01.12.2016 takes the place of the publication of the European patent application. | [2018/15] | Type: | B1 Patent specification | No.: | EP3303400 | Date: | 09.09.2020 | Language: | EN | [2020/37] | Search report(s) | International search report - published on: | EP | 01.12.2016 | Classification | IPC: | C07K16/28, C07K16/46, C12N5/0783, G01N33/50, G01N33/68 | [2018/15] | CPC: |
C07K16/2809 (EP,IL,KR,US);
G01N33/505 (EP,IL,KR,US);
G01N33/68 (IL,KR);
G01N33/6854 (IL,KR,US);
C07K16/2887 (EP,IL,KR,US);
C12N5/0636 (EP,IL,KR,US);
C12Q1/6897 (IL,KR);
G01N33/6845 (EP,IL,KR,US);
C07K2317/31 (EP,IL,KR,US);
| Designated contracting states | AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LI, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, TR [2018/15] | Extension states | BA | Not yet paid | ME | Not yet paid | Validation states | MA | Not yet paid | MD | Not yet paid | Title | German: | ZELLENBASIERTES TESTVERFAHREN ZUM NACHWEIS VON ANTI-CD3-HOMODIMEREN | [2020/15] | English: | CELL-BASED ASSAY FOR DETECTING ANTI-CD3 HOMODIMERS | [2018/15] | French: | TEST CELLULAIRE DE DÉTECTION D'HOMODIMÈRES ANTI-CD3 | [2020/15] |
| Former [2018/15] | ZELLBASIERTER TEST ZUM NACHWEIS VON ANTI-CD3-HOMODIMEREN | ||
| Former [2018/15] | ESSAI À BASE DE CELLULES POUR DÉTECTER DES HOMODIMÈRES ANTI-CD3 | Entry into regional phase | 15.12.2017 | National basic fee paid | 15.12.2017 | Designation fee(s) paid | 15.12.2017 | Examination fee paid | Examination procedure | 13.12.2017 | Date on which the examining division has become responsible | 15.12.2017 | Examination requested [2018/15] | 09.08.2018 | Amendment by applicant (claims and/or description) | 25.01.2019 | Despatch of a communication from the examining division (Time limit: M06) | 05.06.2019 | Reply to a communication from the examining division | 30.03.2020 | Communication of intention to grant the patent | 03.08.2020 | Fee for grant paid | 03.08.2020 | Fee for publishing/printing paid | 03.08.2020 | Receipt of the translation of the claim(s) | Divisional application(s) | EP20190490.1 / EP3795679 | Opposition(s) | 10.06.2021 | No opposition filed within time limit [2021/33] | Fees paid | Renewal fee | 07.05.2018 | Renewal fee patent year 03 | 08.05.2019 | Renewal fee patent year 04 | 30.03.2020 | Renewal fee patent year 05 |
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| Responsibility for the accuracy, completeness or quality of the data displayed under the link provided lies entirely with the Unified Patent Court. | Lapses during opposition Tooltip | HU | 27.05.2016 | AL | 09.09.2020 | CY | 09.09.2020 | CZ | 09.09.2020 | DK | 09.09.2020 | EE | 09.09.2020 | FI | 09.09.2020 | LT | 09.09.2020 | LV | 09.09.2020 | MC | 09.09.2020 | MK | 09.09.2020 | MT | 09.09.2020 | RS | 09.09.2020 | SK | 09.09.2020 | SM | 09.09.2020 | BG | 09.12.2020 | NO | 09.12.2020 | IS | 09.01.2021 | PT | 11.01.2021 | LU | 27.05.2021 | [2024/42] |
| Former [2024/22] | HU | 27.05.2016 | |
| AL | 09.09.2020 | ||
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| SK | 09.09.2020 | ||
| SM | 09.09.2020 | ||
| BG | 09.12.2020 | ||
| NO | 09.12.2020 | ||
| IS | 09.01.2021 | ||
| PT | 11.01.2021 | ||
| LU | 27.05.2021 | ||
| Former [2023/30] | HU | 27.05.2016 | |
| AL | 09.09.2020 | ||
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| BG | 09.12.2020 | ||
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| IS | 09.01.2021 | ||
| PT | 11.01.2021 | ||
| LU | 27.05.2021 | ||
| Former [2023/29] | HU | 27.05.2016 | |
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| BG | 09.12.2020 | ||
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| IS | 09.01.2021 | ||
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| LU | 27.05.2021 | ||
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| IS | 09.01.2021 | ||
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| LU | 27.05.2021 | ||
| Former [2022/07] | AL | 09.09.2020 | |
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| NO | 09.12.2020 | Cited in | International search | [A] WO2014047231 (REGENERON PHARMA et al.) | [XYI] STEL A. ET AL.: "The role of B cell-mediated T cell costimulation in the efficacy of the T cell retargeting bispecific antibody BIS20x3", J. IMMUNOL., vol. 173, no. 10, November 2004 (2004-11-01), pages 6009 - 6016, XP055089413 DOI: http://dx.doi.org/10.4049/jimmunol.173.10.6009 | [Y] SUN L.L. ET AL.: "Anti-CD20/CD3 T cell-dependent bispecific antibody for the treatment of B cell malignancies", SCI. TRANSLAT. MED., vol. 7, no. 287, 287RA70, 13 May 2015 (2015-05-13), pages 1 - 10, XP055241859 DOI: http://dx.doi.org/10.1126/scitranslmed.aaa4802 | [Y] BRISCHWEIN K. ET AL.: "Strictly target cell dependent activation of T cells by bispecific single chain antibody constructs of the Bite Class", J. IMMUNOTHER., vol. 30, no. 8, November 2007 (2007-11-01), pages 798 - 807, XP055276936 DOI: http://dx.doi.org/10.1097/CJI.0b013e318156750c | [A] JUNTTILA T.T. ET AL.: "Antitumor efficacy of a bispecific antibody that targets HER2 and activates T cells", CANCER RES., vol. 74, no. 19, October 2014 (2014-10-01), pages 5561 - 5571, XP055216350 DOI: http://dx.doi.org/10.1158/0008-5472.CAN-13-3622-T | by applicant | US5641870 | EP0404097 | WO9311161 | WO9308829 | US5731168 | WO2009089004 | US4676980 | WO2005035572 | WO03035694 | WO0029004 | WO02051870 | US4816567 | US5693780 | US5500362 | US5821337 | WO9411026 | US5534615 | US5648237 | US5789199 | US5840523 | US7521541 | US5591669 | US5589369 | US5545807 | US5565332 | US5573905 | US5567610 | US5229275 | WO9316185 | US5571894 | US5587458 | WO9404690 | WO9100360 | WO9220373 | EP0308936 | US2006067930 | US5208020 | US5712374 | KABAT ET AL.: "Sequences of Proteins of Immunological Interest", 1991, NATIONAL INSTITUTES OF HEALTH | CHOTHIA; LESK, J. MOL. BIOL., vol. 196, 1987, pages 901 - 917 | ZAPATA ET AL., PROTEIN ENG, vol. 8, no. 10, 1995, pages 1057 - 1062 | PLUCKTHUN: "The Pharmacology of Monoclonal Antibodies", vol. 113, 1994, SPRINGER-VERLAG, pages: 269 - 315 | HOLLINGER ET AL., PROC. NATL. ACAD. SCI. USA, vol. 90, 1993, pages 6444 - 6448 | MILSTEIN; CUELLO, NATURE, vol. 305, 1983, pages 537 | TRAUNECKER ET AL., EMBO J., vol. 10, 1991, pages 3655 | BRENNAN ET AL., SCIENCE, vol. 229, 1985, pages 81 | KOSTELNY ET AL., J. IMMUNOL., vol. 148, no. 5, 1992, pages 1547 - 1553 | GRUBER ET AL., J. IMMUNOL., vol. 152, 1994, pages 5368 | TUTT ET AL., J. IMMUNOL., vol. 147, 1991, pages 60 | WARD, ES ET AL., NATURE, vol. 341, 1989, pages 544 - 546 | DOOLEY, H. ET AL., DEV COMP IMMUNOL, vol. 30, 2006, pages 43 - 56 | MUYLDEMANS S ET AL., TREND BIOCHEM SCI, vol. 26, 2001, pages 230 - 235 | HOLT, LJ ET AL., TRENDS BIOTECHNOL, vol. 21, 2003, pages 484 - 490 | DAVIES, J ET AL., FEBS LETT, vol. 339, 1994, pages 285 - 290 | KOHLER ET AL., NATURE, vol. 256, 1975, pages 495 | CLACKSON ET AL., NATURE, vol. 352, 1991, pages 624 - 628 | MARKS ET AL., J. MOL. BIOL., vol. 222, 1991, pages 581 - 597 | MORRISON ET AL., PROC. NATL. ACAD. SCI. USA, vol. 81, 1984, pages 6851 - 6855 | JONES ET AL., NATURE, vol. 321, 1986, pages 522 - 525 | RIECHMANN ET AL., NATURE, vol. 332, 1988, pages 323 - 329 | PRESTA, CURR. OP. STRUCT. BIOL., vol. 2, 1992, pages 593 - 596 | RAVETCH; KINET, ANNU. REV. IMMUNOL, vol. 9, 1991, pages 457 - 92 | CLYNES ET AL., PROC. NATL. ACAD. SCI. (USA), vol. 95, 1998, pages 652 - 656 | DARON, ANNU. REV. IMMUNOL., vol. 15, 1997, pages 203 - 234 | CAPEL ET AL., IMMUNOMETHODS, vol. 4, 1994, pages 25 - 34 | DE HAAS ET AL., J. LAB. CLIN. MED., vol. 126, 1995, pages 330 - 41 | GUYER ET AL., J. IMMUNOL., vol. 117, 1976, pages 587 | KIM ET AL., J. IMMUNOL., vol. 24, 1994, pages 249 | DE GAST GC ET AL., CANCER IMMUNOL IMMUNOTHER, vol. 40, no. 6, 1995, pages 390 - 396 | BUHMANN R ET AL., BONE MARROW TRANSPLANT., vol. 43, no. 5, 2009, pages 383 - 397 | CHAN JK ET AL., CLIN CANCER RES., vol. 12, no. 6, 2006, pages 1859 - 1867 | CHAMES, P.; BATY, D., MABS, vol. 1, no. 6, 2009, pages 539 - 547 | FOURNIER, P.; SCHIRRMACHER, V., BIODRUGS, vol. 27, no. 1, 2013, pages 35 - 53 | ZWEIFACH A, IMMUNOL REV., vol. 231, no. 1, 2009, pages 160 - 173 | PIPKIN, ME ET AL., IMMUNOL REV., vol. 235, no. 1, 2010, pages 55 - 72 | PARDO, J ET AL., INT IMMUNOL., vol. 15, no. 12, 2003, pages 1441 - 1450 | KROGSGAARD M ET AL., SEMIN IMMUNOL, vol. 15, no. 6, 2003, pages 307 - 315 | PATTU V ET AL., FRONT IMMUNOL., vol. 4, 2013, pages 411 | KLIEGER Y ET AL., EUR J IMMUNOL., vol. 44, no. 1, 2014, pages 58 - 68 | SCHWARTZ JC ET AL., NAT IMMUNOL., vol. 3, no. 5, 2002, pages 427 - 434 | BROWN, WM, CURR OPIN INVESTIG DRUGS, vol. 7, 2006, pages 381 - 388 | FERRAN, C ET AL., EXP NEPHROL, vol. 1, 1993, pages 83 - 89 | MF ET AL., J. LEUKOC. BIOL., vol. 57, 1995, pages 767 - 773 | SHAPIRO VS ET AL., J. IMMUNOL., vol. 161, no. 12, 1998, pages 6455 - 6458 | SHANNON, MF ET AL., J. LEUKOC. BIOL., vol. 57, 1995, pages 767 - 773 | BROGAN J ET AL., RADIAT RES., vol. 177, no. 4, 2012, pages 508 - 513 | MIRAGLIA LJ ET AL., COMB CHEM HIGH THROUGHPUT SCREEN., vol. 14, no. 8, 2011, pages 648 - 657 | NAKAJIMA Y; OHMIYA Y, EXPERT OPIN DRUG DISCOVERY, vol. 5, no. 9, 2010, pages 835 - 849 | PAREKH BS ET AL., MABS, vol. 4, no. 3, 2012, pages 310 - 318 | SVOBODOVA K; CAJTHAM L T., APPL MICROBIOL BIOTECHNOL., vol. 88, no. 4, 2010, pages 839 - 847 | OSAKA, G ET AL., J PHARM SCI., vol. 85, 1996, pages 612 - 618 | NAKAMURA, GR ET AL., J. VIROL., vol. 67, no. 10, 1993, pages 6179 - 6191 | NALDINI, L. ET AL., SCIENCE, vol. 272, 1996, pages 263 - 267 | CHARLTON: "Methods in Molecular Biology", vol. 248, 2003, HUMANA PRESS, pages: 245 - 254 | CARTER ET AL., BIOLTECHNOLOGY, vol. 10, 1992, pages 163 - 167 | GODING: "Monoclonal Antibodies: Principles and Practice", 1986, ACADEMIC PRESS, pages: 59 - 103 | KOZBOR, J. IMMUNOL., vol. 133, 1984, pages 3001 | BRODEUR ET AL.: "Monoclonal Antibody Production Techniques and Applications", 1987, MARCEL DEKKER, INC., pages: 51 - 63 | MUNSON ET AL., ANAL. BIOCHEM., vol. 107, 1980, pages 220 | SKERRA ET AL., CURR. OPINION IN IMMUNOL., vol. 5, 1993, pages 256 - 262 | PLC THUN, IMMUNOL. REVS., vol. 130, 1992, pages 151 - 188 | MCCAFFERTY ET AL., NATURE, vol. 348, 1990, pages 552 - 554 | MARKS ET AL., BIOLTECHNOLOGY, vol. 10, 1992, pages 779 - 783 | WATERHOUSE ET AL., NUC. ACIDS. RES., vol. 21, 1993, pages 2265 - 2266 | MORRISON ET AL., PROC. NATL ACAD. SCI. USA, vol. 81, 1984, pages 6851 | RIECHMANN ET AL., NATURE, vol. 332, 1988, pages 323 - 327 | VERHOEYEN ET AL., SCIENCE, vol. 239, 1988, pages 1534 - 1536 | SIMS ET AL., J. IMMUNOL., vol. 151, 1993, pages 2296 | CHOTHIA ET AL., J. MOL. BIOL., vol. 196, 1987, pages 901 | CARTER ET AL., PROC. NATL. ACAD. SCI. USA, vol. 89, 1992, pages 4285 | PRESTA ET AL., J. IMMUNOL., vol. 151, 1993, pages 2623 | JAKOBOVITS ET AL., PROC. NATL. ACAD. SCI. USA, vol. 90, 1993, pages 2551 | JAKOBOVITS ET AL., NATURE, vol. 362, 1993, pages 255 - 258 | BRUGGERMANN ET AL., YEAR IN IMMUNO, vol. 7, 1993, pages 33 | MCCAFFERTY ET AL., NATURE, vol. 348, 1990, pages 552 - 553 | JOHNSON, KEVIN S.; CHISWELL, DAVID J., CURRENT OPINION IN STRUCTURAL BIOLOGY, vol. 3, 1993, pages 564 - 571 | GRIFFITH ET AL., EMBO J., vol. 12, 1993, pages 725 - 734 | MORIMOTO ET AL., JOURNAL OF BIOCHEMICAL AND BIOPHYSICAL METHODS, vol. 24, 1992, pages 107 - 117 | CARTER ET AL., BIOL1'ECHNOLOGY, vol. 10, 1992, pages 163 - 167 | MILLSTEIN ET AL., NATURE, vol. 305, 1983, pages 537 - 539 | TRAUNECKER ET AL., EMBO J., vol. 10, 1991, pages 3655 - 3659 | SURESH ET AL., METHODS IN ENZYMOLOGY, vol. 121, 1986, pages 210 | CARON ET AL., J. EXP MED., vol. 176, 1992, pages 1191 - 1195 | SHOPES, B. J., IMMUNOL, vol. 148, 1992, pages 2918 - 2922 | WOLFF ET AL., CANCER RESEARCH, vol. 53, 1993, pages 2560 - 2565 | STEVENSON ET AL., ANTI-CANCER DRUG DESIGN, vol. 3, 1989, pages 219 - 230 | CUNNINGHAM; WELLS, SCIENCE, vol. 244, 1989, pages 1081 - 1085 | A. L. LEHNINGER: "Biochemistry", 1975, WORTH PUBLISHERS, pages: 73 - 75 | VITETTA ET AL., SCIENCE, vol. 238, 1987, pages 1098 | GENNARO, A.R.,: "Remington's Pharmaceutical Sciences, 18th edition,", 1990 | SHIPKOVA M, CLIN. CHIM. ACTA, vol. 413, 2012, pages 1338 - 49 | ZIEGLER SF, ET AL., STEM CELLS, vol. 12, no. 5, 1994, pages 465 - 465 |