Granted Patent
B2
US 12,692,320 · App. 17/923,317 · Granted Jul 28, 2026
Bispecific antibodies against CD3 and CD20
Inventors:
Tahamtan Ahmadi (Rydal, PA); Manish Gupta (Skillman, NJ); Tommy R. Li (Edison, NJ); Roberto Oliveri (Copenhagen, DK); Dena DeMarco (Chatham, NJ); Ida Hiemstra (Utrecht, NL); Christopher Chiu (Warren, NJ); Brian Elliott (Hoboken, NJ); Ada Azaryan (North Bethesda, MD)
Assignee:
GENMAB A/S
C07K16/2887A61K31/573A61K39/3955A61K45/06A61P35/00C07K16/2809A61K39/00A61K2039/505A61K2039/545C07K2317/21C07K2317/24C07K2317/31
View Patent ↗
Loading inventors, assignments & file history…
Abstract
The present invention relates to bispecific antibodies (bsAbs) and the use of such antibodies in the treatment of disease in subjects. Moreover, advantageous treatment regimens are provided for the treatment of B-cell Non-Hodgkin Lymphoma (B-NHL).
Claims (37)
1 . A method of treating a B-cell non-Hodgkin lymphoma (B-NHL) in a human subject, the method comprising subcutaneously administering a dose of 0.16 mg of epcoritamab to the subject on day one (1) of treatment and subcutaneously administering a dose of 0.8 mg of epcoritamab to the subject on day eight (8) of treatment,
wherein the subject does not experience cytokine release syndrome (CRS) or experiences manageable cytokine release syndrome of grade 1 or grade 2, and
wherein after day eight (8) of treatment a dose of 48 mg of epcoritamab is subcutaneously administered in intervals to the subject until progressive disease develops or unacceptable toxicity occurs.
2 . The method of claim 1 , wherein 48 mg of epcoritamab is administered subcutaneously to the human subject on days 15 and 22 of treatment.
3 . The method of claim 1 , wherein said B-NHL is selected from the group consisting of diffuse large B-cell lymphoma (DLBCL), high-grade B-cell lymphoma (HGBCL), primary mediastinal large B-cell lymphoma (PMBCL), mantle cell lymphoma (MCL), follicular lymphoma (FL), marginal-zone lymphoma (MZL), chronic lymphocytic leukemia (CLL), and small lymphocytic lymphoma (SLL).
4 . The method of claim 3 , wherein said B-NHL is diffuse large B-cell lymphoma (DLBCL).
5 . The method of claim 3 , wherein said B-NHL is mantle cell lymphoma (MCL).
6 . The method of claim 3 , wherein said B-NHL is follicular lymphoma (FL).
7 . The method of claim 3 , wherein said B-NHL is marginal-zone lymphoma (MZL).
8 . The method of claim 3 , wherein said B-NHL is small lymphocytic lymphoma (SLL).
9 . The method of claim 3 , wherein said B-NHL is relapsed or refractory B-NHL.
10 . The method of claim 3 , wherein said B-NHL is chronic lymphocytic lymphoma (CLL).
11 . The method of claim 1 , wherein prior to the day 1 of treatment with epcoritamab the human subject has received at least one prior line of treatment for the B-NHL.
12 . The method of claim 1 , wherein prior to the day 1 of treatment with epcoritamab the human subject has received at least two prior lines of treatment for the B-NHL.
13 . The method of claim 2 , wherein said B-NHL is selected from the group consisting of diffuse large B-cell lymphoma (DLBCL), high-grade B-cell lymphoma (HGBCL), primary mediastinal large B-cell lymphoma (PMBCL), mantle cell lymphoma (MCL), follicular lymphoma (FL), marginal-zone lymphoma (MZL), chronic lymphocytic leukemia (CLL), and small lymphocytic lymphoma (SLL), and wherein the patient achieves a complete response (CR).
14 . The method of claim 13 , wherein said B-NHL is diffuse large B-cell lymphoma (DLBCL).
15 . The method of claim 13 , wherein said B-NHL is mantle cell lymphoma (MCL).
16 . The method of claim 13 , wherein said B-NHL is follicular lymphoma (FL).
17 . The method of claim 13 , wherein said B-NHL is marginal-zone lymphoma (MZL).
18 . The method of claim 13 , wherein said B-NHL is small lymphocytic lymphoma (SLL).
19 . The method of claim 13 , wherein said B-NHL is relapsed or refractory B-NHL.
20 . The method of claim 13 , wherein said B-NHL is chronic lymphocytic lymphoma (CLL).
21 . A method of treating a B-cell non-Hodgkin lymphoma (B-NHL) in a human subject, the method comprising administering epcoritamab subcutaneously in 28-day cycles, wherein:
a) a priming dose of 0.16 mg is administered on day 1, an intermediate dose of 0.8 mg is administered on day 8, and a full dose of 48 mg is administered on days 15 and 22 of the first cycle;
b) a full dose of 48 mg is administered on days 1, 8, 15 and 22 of cycles 2-3;
c) a full dose of 48 mg is administered on days 1 and 15 of cycles 4-9; and
d) a full dose of 48 mg is administered on day 1 of subsequent cycles until progressive disease develops or unacceptable toxicity occurs.
22 . The method of claim 21 , wherein said B-NHL is selected from the group consisting of diffuse large B-cell lymphoma (DLBCL), high-grade B-cell lymphoma (HGBCL), primary mediastinal large B-cell lymphoma (PMBCL), mantle cell lymphoma (MCL), follicular lymphoma (FL), marginal-zone lymphoma (MZL), chronic lymphocytic leukemia (CLL), and small lymphocytic lymphoma (SLL).
23 . The method of claim 22 , wherein said B-NHL is diffuse large B-cell lymphoma (DLBCL).
24 . The method of claim 22 , wherein said B-NHL is mantle cell lymphoma (MCL).
25 . The method of claim 22 , wherein said B-NHL is follicular lymphoma (FL).
26 . The method of claim 22 , wherein said B-NHL is marginal-zone lymphoma (MZL).
27 . The method of claim 22 , wherein said B-NHL is small lymphocytic lymphoma (SLL).
28 . The method of claim 22 , wherein said B-NHL is relapsed or refractory B-NHL.
29 . The method of claim 22 , wherein said B-NHL is chronic lymphocytic lymphoma (CLL).
30 . The method of claim 21 , wherein prior to the day 1 of treatment with epcoritamab the human subject has received at least one prior line of treatment for the B-NHL.
31 . The method of claim 21 , wherein prior to the day 1 of treatment with epcoritamab the human subject has received at least two prior lines of treatment for the B-NH.
Assignments (3)
SECURITY INTEREST
Recorded Dec 15, 2025
From: GENMAB A/S; GENMAB B.V.; GENMAB HOLDING B.V.
To: MORGAN STANLEY SENIOR FUNDING, INC.
Reel/Frame 073933/0597 →
NOTICE OF GRANT OF SECURITY INTEREST IN PATENTS
Recorded Dec 15, 2025
From: GENMAB A/S; GENMAB B.V.; GENMAB HOLDING B.V.
To: WILMINGTON TRUST, NATIONAL ASSOCIATION
Reel/Frame 073949/0722 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Nov 30, 2022
From: AHMADI, TAHAMTAN; CHIU, CHRISTOPHER; ELLIOTT, BRIAN; AZARYAN, ADA; GUPTA, MANISH; LI, TOMMY; OLIVERI, ROBERTO; DEMARCO, DENA; HIEMSTRA, IDA
To: GENMAB A/S
Reel/Frame 062025/0129 →
Continuity (4)
Provisional Application
63022212
· May 8, 2020
Provisional Application
63078667
· Sep 15, 2020
Provisional Application
63121690
· Dec 4, 2020
Related Publication
20230227570A1
· Jul 20, 2023
References Cited (400)
US 4946778A
· Ladner et al.
· 1990
[cited by applicant]
US 5589466A
· Felgner et al.
· 1996
[cited by applicant]
US 5731168A
· Carter et al.
· 1998
[cited by applicant]
US 5736137A
· Anderson et al.
· 1998
[cited by applicant]
US 5739277A
· Presta et al.
· 1998
[cited by applicant]
US 5973972A
· Kwon et al.
· 1999
[cited by applicant]
US 6077835A
· Hanson et al.
· 2000
[cited by applicant]
US 7262028B2
· Van Berkel et al.
· 2007
[cited by applicant]
US 7375118B2
· Sircar et al.
· 2008
[cited by applicant]
US 7612181B2
· Wu et al.
· 2009
[cited by applicant]
US 7951918B2
· Glaser et al.
· 2011
[cited by applicant]
US 8236308B2
· Kischel et al.
· 2012
[cited by applicant]
US 9150663B2
· Labrijn et al.
· 2015
[cited by applicant]
US 9212230B2
· Schuurman et al.
· 2015
[cited by applicant]
US 20040167319A1
· Teeling et al.
· 2004
[cited by applicant]
US 20100015513A1
· Nakahama et al.
· 2010
[cited by applicant]
US 20100105874A1
· Schuurman et al.
· 2010
[cited by applicant]
US 20100155133A1
· Makwinski et al.
· 2010
[cited by applicant]
US 20100297106A1
· Sloey et al.
· 2010
[cited by applicant]
US 20120301400A1
· Williams et al.
· 2012
[cited by applicant]
US 20130039913A1
· Labrijn et al.
· 2013
[cited by applicant]
US 20130216556A1
· Fowler et al.
· 2013
[cited by applicant]
US 20140088295A1
· Smith et al.
· 2014
[cited by applicant]
US 20140303356A1
· Gramer et al.
· 2014
[cited by applicant]
US 20150071943A1
· Bishop et al.
· 2015
[cited by applicant]
US 20150166661A1
· Chen et al.
· 2015
[cited by applicant]
US 20150209430A1
· Benedict et al.
· 2015
[cited by applicant]
US 20150225479A1
· Huille et al.
· 2015
[cited by applicant]
US 20150337049A1
· Labrijn et al.
· 2015
[cited by applicant]
US 20160046727A1
· Labrijn et al.
· 2016
[cited by applicant]
US 20160159330A1
· Anderson et al.
· 2016
[cited by applicant]
US 20160168247A1
· Van Den Brink et al.
· 2016
[cited by applicant]
US 20160199399A1
· Knudsen
· 2016
[cited by applicant]
US 20160333095A1
· Van Den Brink et al.
· 2016
[cited by applicant]
US 20170233497A1
· Labrijn et al.
· 2017
[cited by applicant]
US 20170349657A1
· Saville et al.
· 2017
[cited by applicant]
US 20170355767A1
· Engelberts et al.
· 2017
[cited by applicant]
US 20200123255A1
· Van Den Brink et al.
· 2020
[cited by applicant]
US 20200199231A1
· Engelberts et al.
· 2020
[cited by applicant]
US 20210032358A1
· Valbjoern et al.
· 2021
[cited by applicant]
US 20210230301A1
· De Jong et al.
· 2021
[cited by applicant]
US 20220088070A1
· Albertson et al.
· 2022
[cited by applicant]
US 20220112309A1
· Elliott et al.
· 2022
[cited by applicant]
US 20220389101A1
· Rademaker et al.
· 2022
[cited by applicant]
US 20220411505A1
· Valbjoern et al.
· 2022
[cited by applicant]
US 20230227495A1
· Gramer et al.
· 2023
[cited by applicant]
US 20230227570A1
· Ahmadi et al.
· 2023
[cited by applicant]
US 20230241211A1
· Chiu et al.
· 2023
[cited by applicant]
US 20230303693A1
· Chiu et al.
· 2023
[cited by applicant]
US 20230310599A1
· Benonisson et al.
· 2023
[cited by applicant]
US 20230312757A1
· Elliott et al.
· 2023
[cited by applicant]
US 20230312758A1
· Elliott et al.
· 2023
[cited by applicant]
US 20230312759A1
· Elliott et al.
· 2023
[cited by applicant]
US 20230322947A1
· Labrijn et al.
· 2023
[cited by applicant]
US 20230355753A1
· Elliott et al.
· 2023
[cited by applicant]
US 20230357440A1
· Elliott et al.
· 2023
[cited by applicant]
US 20230374131A1
· Van Den Brink et al.
· 2023
[cited by applicant]
US 20240034812A1
· Elliott et al.
· 2024
[cited by applicant]
US 20240174761A1
· Elliott et al.
· 2024
[cited by applicant]
US 20240209117A1
· Labrijn et al.
· 2024
[cited by applicant]
US 20240301078A1
· Elliott et al.
· 2024
[cited by applicant]
US 20240368297A1
· Li et al.
· 2024
[cited by applicant]
US 20240400685A1
· Hibbert et al.
· 2024
[cited by applicant]
US 20240409656A1
· Kilavuz et al.
· 2024
[cited by applicant]
US 20250101102A1
· Chiu et al.
· 2025
[cited by applicant]
US 20250115665A1
· Chiu et al.
· 2025
[cited by applicant]
US 20250304689A1
· Elliott et al.
· 2025
[cited by applicant]
CN 101309703A
· 2008
[cited by applicant]
CN 102250246A
· 2011
[cited by applicant]
CN 1729203B
· 2014
[cited by applicant]
CN 103796677B
· 2014
[cited by applicant]
CN 104271122A
· 2015
[cited by applicant]
CN 104922668A
· 2015
[cited by applicant]
CN 104922688A
· 2015
[cited by applicant]
CN 103703024B
· 2017
[cited by applicant]
CN 107660214B
· 2018
[cited by applicant]
EA 033992B1
· 2018
[cited by applicant]
EA 201891694A1
· 2019
[cited by applicant]
EP 0629240A1
· 1994
[cited by applicant]
EP 1870459A1
· 2007
[cited by applicant]
EP 4137574A1
· 2023
[cited by applicant]
JP 2009511521A
· 2009
[cited by applicant]
JP 2010527621A
· 2010
[cited by applicant]
JP 2010527622A
· 2010
[cited by applicant]
JP 2013531470A
· 2013
[cited by applicant]
WO 9222653A1
· 1992
[cited by applicant]
WO 9850431A2
· 1998
[cited by applicant]
WO 200046147A2
· 2000
[cited by applicant]
WO 0070087A1
· 2000
[cited by applicant]
WO 2003074569A2
· 2003
[cited by applicant]
WO 2004035607A2
· 2004
[cited by applicant]
WO 2005004809A2
· 2005
[cited by applicant]
WO 2005061547A2
· 2005
[cited by applicant]
WO 2005103081A2
· 2005
[cited by applicant]
WO 2007042261A2
· 2007
[cited by applicant]
WO 2007059782A1
· 2007
[cited by applicant]
WO 2007110205A2
· 2007
[cited by applicant]
WO 2008003116A2
· 2008
[cited by applicant]
WO 2008119353A1
· 2008
[cited by applicant]
WO 2008119567A2
· 2008
[cited by applicant]
WO 2008145137A2
· 2008
[cited by applicant]
WO 2008145140A2
· 2008
[cited by applicant]
WO 2008145141A1
· 2008
[cited by applicant]
WO 2008157379A2
· 2008
[cited by applicant]
WO 2009009407A1
· 2009
[cited by applicant]
WO 2009040562A1
· 2009
[cited by applicant]
WO 2009058383A2
· 2009
[cited by applicant]
WO 2009080254A1
· 2009
[cited by applicant]
WO 2009089004A1
· 2009
[cited by applicant]
WO 2010015792A1
· 2010
[cited by applicant]
WO 2010026923A1
· 2010
[cited by applicant]
WO 2010059315A1
· 2010
[cited by applicant]
WO 2010080538A1
· 2010
[cited by applicant]
WO 2010111625A1
· 2010
[cited by applicant]
WO 2010129304A2
· 2010
[cited by applicant]
WO 2010134666A1
· 2010
[cited by applicant]
WO 2011014659A2
· 2011
[cited by applicant]
WO 2011028952A1
· 2011
[cited by applicant]
WO 2011066501A1
· 2011
[cited by applicant]
WO 2011069104A2
· 2011
[cited by applicant]
WO 2011090762A1
· 2011
[cited by applicant]
WO 2011117329A1
· 2011
[cited by applicant]
WO 2011131746A2
· 2011
[cited by applicant]
WO 11143545A1
· 2011
[cited by applicant]
WO 2012023053A2
· 2012
[cited by applicant]
WO 2012025525A1
· 2012
[cited by applicant]
WO 2012025530A1
· 2012
[cited by applicant]
WO 2012058768A1
· 2012
[cited by applicant]
WO 2012073985A1
· 2012
[cited by applicant]
WO 2012143524A2
· 2012
[cited by applicant]
WO 2012158818A2
· 2012
[cited by applicant]
WO 2012162067A2
· 2012
[cited by applicant]
WO 2013026833A1
· 2013
[cited by applicant]
WO 2013060867A2
· 2013
[cited by applicant]
WO 2013123114A2
· 2013
[cited by applicant]
WO 2013157953A1
· 2013
[cited by applicant]
WO 2014047231A1
· 2014
[cited by applicant]
WO 2014081202A1
· 2014
[cited by applicant]
WO 2014108483A1
· 2014
[cited by applicant]
WO 2014131694A1
· 2014
[cited by applicant]
WO 2014131711A1
· 2014
[cited by applicant]
WO 2015001085A1
· 2015
[cited by applicant]
WO 2015006749A2
· 2015
[cited by applicant]
WO 2015143079A1
· 2015
[cited by applicant]
WO 2016007854A1
· 2016
[cited by applicant]
WO 2016081490A1
· 2016
[cited by applicant]
WO 2016110576A1
· 2016
[cited by applicant]
WO 2016164404A1
· 2016
[cited by applicant]
WO 2017123650A2
· 2017
[cited by applicant]
WO 2017136433A1
· 2017
[cited by applicant]
WO 2017210485A1
· 2017
[cited by applicant]
WO 2018165631A1
· 2018
[cited by applicant]
WO 2019034580A1
· 2019
[cited by applicant]
WO 2019155008A1
· 2019
[cited by applicant]
WO 2019224715A1
· 2019
[cited by applicant]
WO 2019224717A2
· 2019
[cited by applicant]
WO 2020088605A1
· 2020
[cited by applicant]
WO 2020102770A1
· 2020
[cited by applicant]
WO 2021028587A1
· 2021
[cited by applicant]
WO 2021224499A1
· 2021
[cited by applicant]
WO 2022053653A1
· 2022
[cited by applicant]
WO 2022053654A1
· 2022
[cited by applicant]
WO 2022053655A1
· 2022
[cited by applicant]
WO 2022053656A1
· 2022
[cited by applicant]
WO 2022053657A1
· 2022
[cited by applicant]
WO 2022053658A1
· 2022
[cited by applicant]
WO 2022098628A2
· 2022
[cited by applicant]
WO 2023198839A2
· 2023
[cited by applicant]
Lugtenburg et al. First-in-Human, Phase 1/2 Trial to Assess the Safety andClinical Activity of Subcutaneous GEN3013 (DuoBody (R)-CD3xCD20) in B-Cell Non-Hodgkin Lymphomas. (Blood (2019) 134 (Supplement_1) (Year: 2019).
[cited by examiner]
NCT03625037 (Viewing V3 (Sep. 13, 2018)). First-in-Human (FIH) Trial in Patients With Relapsed, Progressive or Refractory B-Cell Lymphoma (EPCORE™ NHL-1) (Year: 2018).
[cited by examiner]
Withoff, S. et al., Characterization of BIS20x3, a bi-specific antibody activating and retargeting T-cells to CD20-positve B-cells,: British Journal of Cancer, vol. 84(8):1115-1121 (2001).
[cited by applicant]
Committee for Medicinal Products for Human Use (CHMP), “Guideline on the evaluation of anticancer medicinal products in man,” European Medicines Agency, Science Medicines Health, EMA/CHMP/205/95 Rev.5, Sep. 22, 2017, 43…
[cited by applicant]
Morschhauser F. et al. “Rituximab plus Lenalidomide in Advanced Untreated Follicular Lymphoma” New England Journal of Medicine, vol. 379(10): 934-947 (2018).
[cited by applicant]
Muller, D, et al., “Bispecific antibodies for cancer immunotherapy: Current perspectives,” BioDrugs, vol. 24(2): 89-98 (2010).
[cited by applicant]
Niemann, C et al., “Venetoclax and Ibrutinib for Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia (R/R CLL)—15-Month Safety, Response and MRD Evaluation: Third Interim Analysis from the Phase II Vision HO1…
[cited by applicant]
Oken, M et al., “Toxicity and response criteria of the Eastern Cooperative Oncology Group,” Am J Clin Oncol, vol. 5(6): 649-655 (1982).
[cited by applicant]
Olejniczak, S et al., “A quantitative exploration of surface antigen expression in common B-cell malignancies using flow cytometry,” Immunol Invest, vol. 35(1): 93-114 (2006).
[cited by applicant]
Paraplatin®, retrieved on Feb. 9, 2022 www.accessdata.fda.gov/drugsatfda_docs/label/2010/020452s005lbl.pdf, 21 pages.
[cited by applicant]
Patel K. et al., “Preliminary Safety and Anti-Tumor Activity of XmAb13676, an Anti-CD20 x Anti-CD3 Bispecific Antibody, in Patients with Relapsed/Refractory Non-Hodgkin's Lymphoma and Chronic Lymphocytic Leukemia”, Bloo…
[cited by applicant]
Mondello, P. et al. “Bendamustine plus Rituximab Versus R-CHOP as First-Line Treatment for Patients with Follicular Lymphoma Grade 3A: Evidence from a Multicenter, Retrospective Study,” The Oncologist, vol. 23(4):454-46…
[cited by applicant]
Pedersen, I. et al., “The chimeric anti-CD20 antibody rituximab induces apoptosis in B-cell chronic lymphocytic leukemia cells through a p38 mitogen activated protein-kinase-dependent mechanism,” Blood, vol. 99(4): 1314…
[cited by applicant]
Perks, B. et al., “Bispecific antibodies direct the immune system against blood; cancers,” The Pharmaceutical Journal, URI: 20068566: 2 pages (2015).
[cited by applicant]
Prescribing Information for Cyclophosphamide, Retrieved on Feb. 9, 2022, www.accessdata.fda.gov/drugsatfda_docs/label/2013/012141s090,012142s112lbl.pdf, 18 pages.
[cited by applicant]
Prescribing Information for Eloxatin Retrieved on Feb. 9, 2022, www.accessdata.fda.gov/drugsatfda_docs/label/2020/021759s023lbl.pdf, 42 pages.
[cited by applicant]
Prescribing Information for Gemzar, Retrieved on Feb. 9, 2022, www.accessdata.fda.gov/drugsatfda_docs/label/2014/020509s077lbl.pdf 18 pages.
[cited by applicant]
Prescribing Information For Infugem, Retrieved on Feb. 9, 2022, www.accessdata.fda.gov/drugsatfda_docs/label/2018/208313Orig1s000lbl.pdf, 30 pages.
[cited by applicant]
Prescribing Information for Rituxan®, Retrieved on Feb. 9, 2022, www.accessdata.fda.gov/drugsatfda_docs/label/2013/103705s5414lbl.pdf, 41 pages.
[cited by applicant]
Prescribing Information for Treanda, 11 pages, (2008) retrieved on Feb. 9, 2022 https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022303lbl.pdf.
[cited by applicant]
Prescribing Infromation for Bendeka Retrieved on Feb. 9, 2022, www.accessdata.fda.gov/drugsatfda_docs/label/2015/208194s000lbl.pdf. 23 pages.
[cited by applicant]
Prescribing Infromation for Revlimid, Retrieved on Feb. 9, 2022, www.accessdata.fda.gov/drugsatfda_docs/label/2013/021880s034lbl.pdf, 33 pages.
[cited by applicant]
Prevodnik, V. et al., “The predictive significance of CD20 expression in; B-cell lymphomas,” Diagn Pathol., vol. 6(33): 6 pages (2011).
[cited by applicant]
Shipp et al., “A predictive model for aggressive non-Hodgkin's lymphoma,” N Engl J Med., vol. 329(14): 987-994 (1993).
[cited by applicant]
Shen, Qiu-Dan, et al. “Gemcitabine-oxaliplatin plus rituximab (R-GemOx) as first-line treatment in elderly patients with diffuse large B-cell lymphoma: a single-arm, open-label, phase 2 trial,” Lancet Haematology, vol. …
[cited by applicant]
Relander, T. et al., “Prognostic factors in follicular lymphoma,” J Clin Oncol, vol. 28(17): 2902-2913 (2010).
[cited by applicant]
Rigacci, L. et al., “Oxaliplatin-based chemotherapy (dexamethasone, high-dose cytarabine, and oxaliplatin) ± rituximab is an effective salvage regimen in patients with relapsed or refractory lymphoma,” Cancer, vol. 116(…
[cited by applicant]
Rossi, D et al., “Integrated mutational and cytogenetic analysis identifies new prognostic subgroups in chronic lymphocytic leukemia,” Blood, vol. 121(8):1403-1412 (2013).
[cited by applicant]
Rudikoff, S. et al., “Single amino acid substitution altering antigen-binding specificity,” PNAS, vol. 79(6):1979-83 (1982).
[cited by applicant]
Rummel, M. et al.,“Bendamustine plus rituximab versus CHOP plus rituximab as first-line treatment for patients with indolent and mantle-cell lymphomas: an open-label, multicentre, randomised, phase 3 non-inferiority tri…
[cited by applicant]
Safety and Efficacy Trial of Epcoritamab Combinations in Subjects With B-cell Non-Hodgkin Lymphoma, https://clinicaltrials.gov/ct2/show/NCT04663347 ClinicalTrials.gov Identifier: NCT04663347, Nov. 3, 2021, 13 pages.
[cited by applicant]
Salles, G. et al., “Efficacy and safety of idelalisib in patients with relapsed, rituximab- and alkylating agent-refractory follicular lymphoma: a subgroup analysis of a phase 2 study,” Haematologica, vol. 102(4):e159 (…
[cited by applicant]
Sarkozy, C. et al., “New drugs for the management of relapsed or refractory diffuse large B-cell lymphoma,” Ann Lymphoma, vol. 3(10) 19 pages (2019).
[cited by applicant]
Sehn, L. et al., “The revised International Prognostic Index (R-IPI) is a better predictor of outcome than the standard IPI for patients with diffuse large B-cell lymphoma treated with R-CHOP,” Blood, vol. 109(5):1857-1…
[cited by applicant]
Seymour, JF et al., “Venetoclax-Rituximab in Relapsed or Refractory Chronic Lymphocytic Leukemia,” N Engl J Med, vol. 378(12): 1107-1120 (2018).
[cited by applicant]
Siegel, R et al., “Cancer statistics, 2019,” 2019, CA Cancer J Clin, vol. 69(1):7-34 (2019).
[cited by applicant]
Smith, E. et al.“A novel, native-format bispecific antibody triggering T-cell killing of B-cells is robustly active in mouse tumor models and cynomolgus monkeys,” Nat. Sci. Rep., vol. 5:17943: 12 pages (2015).
[cited by applicant]
Staerz, U. et al., “Hybrid antibodies can target sites for attack by T cells,” 1985, Nature, vol. 314(6012):628-31(1985).
[cited by applicant]
Tam, C. et al., “Ibrutinib (Ibr) Plus Venetoclax (Ven) for First-Line Treatment of Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL): Results from the MRD Cohort of the Phase 2 Captivate Study,” Blood,…
[cited by applicant]
Tixier, F et al., “Comparative toxicities of 3 platinum-containing chemotherapy regimens in relapsed/refractory lymphoma patients,” Hematol Oncol., vol. 35(4):584-590 (2016).
[cited by applicant]
Uhm, J., “Recent advances in chronic lymphocytic leukemia therapy,” Blood Res Seoul, vol. 55(S1):S72-S82(2020).
[cited by applicant]
Vajdos, F. et al., “Comprehensive functional maps of the antigen-binding site of an anti-ErbB2 antibody obtained with shotgun scanning mutagenesis,” J Mol Biol., vol. 320(2): 415-28 (2002).
[cited by applicant]
Van der Horst, H. et al., “Duobody-CD3xCD20 Induces Potent Anti-Tumor Activity in Malignant Lymph Node B Cells from Patients with DLBCL, FL and MCL Ex Vivo, Irrespective of Prior Treatment with CD20 Monoclonal Antibodie…
[cited by applicant]
Varadarajan I, et al., “Management of Cytokine Release Syndrome,” Chimeric Antigen receptor T-cell therapies for Cancer, Chapter 5 :45-64 (2020).
[cited by applicant]
VinCRIStine Sulfate Rx only Injection, USP, Retrieved on Feb. 9, 2022, www.accessdata.fda.gov/drugsatfda_docs/label/2014/071484s042lbl.pdf, 9 pages.
[cited by applicant]
Wagner-Johnston, N. et al., “Outcomes of transformed follicular lymphoma in the modern era: a report from the National LymphoCare Study (NLCS),” Blood, vol. 126(7): 851-857 (2015).
[cited by applicant]
Wierda, W et al., “Multivariable model for time to first treatment in patients with chronic lymphocytic leukemia,” Journ Clin Oncol., vol. 29(31): 4088-4095 (2011).
[cited by applicant]
Wolchok, J et al., “Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria,” Clin Cancer Res, vol. 15(23): 7412-7420 (2009).
[cited by applicant]
Xiong, D. et al., “Efficient inhibition of human B-cell lymphoma xenografts with an anti-CD20 x anti-CD3 bispecific diabody,” Cancer Letters., vol. 177(1):29-39 (2002).
[cited by applicant]
Zenz, T. et al., “From pathogenesis to treatment of chronic lymphocytic leukaemia,” Nat Rev Cancer, vol. 10(1):37-50 (2010).
[cited by applicant]
Adriamycin (DOXOrubicin HCl) for Injection, retieved on Feb. 9, 2022 www.accessdata.fda.gov/drugsatfda_docs/label/2012/062921s022lbl.pdf, 1 page.
[cited by applicant]
Almasri, N et al., “Reduced expression of CD20 antigen as a characteristic marker for chronic lymphocytic leukemia,” Am J Hematol, vol. 40(4):259-63 (1992).
[cited by applicant]
Amgen, Blinatumomab prescribing information and medication guide, Dec. 2014, 24 pages.
[cited by applicant]
Bacac, M. et al., “CD20-TCB with obinutuzumab pretreatment as next generation treatment of hematological malignancies,” Clin Cancer Res., vol. 24(19):4785-4797 (2018).
[cited by applicant]
Barrington, S. et al., “Role of imaging in the staging and response assessment of lymphoma: consensus of the International Conference on Malignant Lymphomas Imaging Working Group,” J Clin Oncol., vol. 32(27):3048-58 (20…
[cited by applicant]
Bedouelle, H. et al., “Diversity and junction residues as hotspots of binding energy in an antibody neutralizing the dengue virus,” FEBS J., vol. 273(1):34-46 (2006).
[cited by applicant]
Berek, J. et al., “Catumaxomab for the treatment of malignant ascites in patients with chemotherapy-refractory ovarian cancer: a phase II study,” Int. J. Gynecol. Cancer, vol. 24(9): 1583-1589 (2014).
[cited by applicant]
Brown, M. et al., “Tolerance of single, but not multiple, amino acid replacements in antibody VH CDR 2: a means of minimizing B cell wastage from somatic hypermutation?,” J Immunol., vol. 156(9):3285-91 (1996).
[cited by applicant]
Burger, J. et al., “Randomized trial of ibrutinib vs ibrutinib plus rituximab in patients with chronic lymphocytic leukemia,” Blood, vol. 133(10):1011-1019 (2019).
[cited by applicant]
Casulo, C. et al., “Autologous Transplantation in Follicular Lymphoma with Early Therapy Failure: A National LymphoCare Study and Center for International Blood and Marrow Transplant Research Analysis,” Biol Bood Marrow…
[cited by applicant]
Cheson, B. et al., “Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification,” J Clin Oncol., vol. 32(27):3059-68 (2014).
[cited by applicant]
Cheson, B. et al., “Refinement of the Lugano Classification lymphoma response criteria in the era of immunomodulatory therapy,” Blood, vol. 128(21):2489-96 (2016).
[cited by applicant]
Chiorazzi, N. et al., “Chronic lymphocytic leukemia,” N Engl J Med., vol. 352(8):804-15. (2005).
[cited by applicant]
Chu, S. et al., “3111 Immunotherapy with Long-Lived Anti-CD20 x Anti-CD3 Bispecific Antibodies Stimulates Potent T Cell-Mediated Killing of Human B Cell Lines and of Circulating and Lymphoid B Cells in Monkeys: A Potent…
[cited by applicant]
CLL-IPI, “An international prognostic index for patients with chronic lymphocytic leukaemia (CLL-IPI): a meta-analysis of individual patient data,” Lancet Oncol., vol. 17(6):779-790 (2016).
[cited by applicant]
Coiffier, K. et al., “Guidelines for the management of pediatric and adult tumor lysis syndrome: an evidence-based review,” J Clin Oncol., vol. 26(16):2767-2708 (2008).
[cited by applicant]
Colman, P., “Effects of amino acid sequence changes on antibody-antigen interactions,” Res Immunol., vol. 145(1):33-6 (1994).
[cited by applicant]
Cytarabine—cytarabine injection, solution Hospira, Inc., lebeling, retrieved on Feb. 9, 2022, labeling.pfizer.com/ShowLabeling.aspx?id=4397.
[cited by applicant]
D'Arena, G et al., “Quantitative flow cytometry for the differential diagnosis of leukemic B-cell chronic lymphoproliferative disorders,” Am J Hematol, vol. 64(4): 275-281 (2000).
[cited by applicant]
Dexamethasone Sodium Phosphate Label, Retrieved on Feb. 9, 2022, www.accessdata.fda.gov/drugsatfda_docs/label/2014/40572s002lbledt.pdf, 2 pages.
[cited by applicant]
Doxorubicin Hydrochloride for Injection, usp, retrieved on Feb. 9, 2022 www.accessdata.fda.gov/drugsatfda_docs/label/2010/050467s070lbl.pdf, 22 pages.
[cited by applicant]
Fisher, K. et al., “Venetoclax and Obinutuzumab in Patients with CLL and Coexisting Conditions,” N Engl J Med., vol. 380 (23):2225-2236 (2019).
[cited by applicant]
Fitzmaurice, C et al., “Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life-Years for 29 Cancer Groups, 1990 to 2016: A Systematic An…
[cited by applicant]
Garber, K., “Bispecific antibodies rise again,” Nat. Rev. Drug Discov., vol. 13(11): 799-801 (2014).
[cited by applicant]
GEN3013 Trial in Patients With Relapsed, Progressive or Refractory B-Cell Lymphoma, https://clinicaltrials.gov/ct2/show/study/NCT03625037, GEN3013 Trial in Patients With Relapsed . . . —Full Text View—ClinicalTrials.pdf…
[cited by applicant]
Ginaldi, L. et al., “Levels of expression of CD19 and CD20 in chronic B cell leukaemias,” J Clin Pathol., vol. 51(5): 364-369 (1988).
[cited by applicant]
Gisselbrecht, C et al., “Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era,” J Clin Oncol., vol. 28 (27): 4184-90 (2010).
[cited by applicant]
Goede, V et al., “Obinutuzumab plus chlorambucil in patients with CLL and coexisting conditions,” N Engl J Med., vol. 370(12):1101-10 (2014).
[cited by applicant]
Gokarn Y. R. et al., “Self-buffering antibody formulations,” Journal of Pharmaceutical Sciences, American Chemical Society and American Pharmaceutical Association US, vol. 97(8): 3051-66 (2008).
[cited by applicant]
Hallek, M. et al., “Chronic lymphocytic leukaemia,” The Lancet, vol. 391(10129):1524-1537 (2018).
[cited by applicant]
Hallek, M. et al., “Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, phase 3 trial,” 2010, Lancet, vol. 376 (9747): 1164-1174 (2010).
[cited by applicant]
Hiddemann, W. et al., “Frontline therapy with rituximab added to the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) significantly improves the outcome for patients with advanced-stage f…
[cited by applicant]
Howard, S. et al., “The tumor lysis syndrome,” N Engl J Med, vol. 364(19): 1844-1854 (2011).
[cited by applicant]
International Search Report and Written Opinion, PCT/EP2020/072927, dated Nov. 18, 2020, 10 pages.
[cited by applicant]
Ito K et al., “Influence of R-CHOP Therapy on Immune System Restoration in Patients with B-Cell Lymphoma,” Oncology, vol. 91(6):302-310 (2016).
[cited by applicant]
Jabbour, E. et al., “Phase II Study Of The Hyper-CVAD Regimen In Combination With Ofatumumab As Frontline Therapy For Adults With CD-20 Positive Acute Lymphoblastic Leukemia (ALL),” Blood, vol. 122(21):2664: 5 pages (20…
[cited by applicant]
Jardin F., “ Improving R-CHOP in diffuse large B-cell lymphoma is still a challenge” Lancet Oncology, vol. 20 (5): 605-606 (2019).
[cited by applicant]
Jurinovic, V et al., “Autologous Stem Cell Transplantation for Patients with Early Progression of Follicular Lymphoma: A Follow-Up Study of 2 Randomized Trials from the German Low Grade Lymphoma Study Group,” Biol Blood…
[cited by applicant]
Kang J, et al, “Rapid formulation Development for Monoclonal Antibodies” Bioprocess International, 6 page, Apr. 12, 2016.
[cited by applicant]
Khan, Y et al., “Acalabrutinib and its use in treatment of chronic lymphocytic leukemia,” Future Oncol., vol. 15(6): 579-589 (2019).
[cited by applicant]
Kontermann, R. et al., “Bispecific Antibodies,” Drug Discov Today, vol. 20(7):838-847 (2015).
[cited by applicant]
Konternamm R., “Dual targeting strategies with bispecific antibodies” mAbs vol. 4(2):182-197 (2012).
[cited by applicant]
Kurokawa, T. et al., “Immune reconstitution of B-cell lymphoma patients receiving CHOP-based chemotherapy containing rituximab,” Hematol Oncol., vol. 29(1): 5-9 (2011).
[cited by applicant]
Labrijn, AF et al., “Efficient generation of stable bispecific IgG1 by controlled Fab-arm exchange,” PNAS, vol. 110(13):5145-5150 (2013).
[cited by applicant]
Labrijn, A. et al., “Controlled Fab-arm exchange for the generation of stable bispecific IgG1,” Nature Protocols, vol. 9(10): 2450-63 (2014).
[cited by applicant]
Lee, D et al., “ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells,” Biol Blood Marrow Transplant, vol. 25(4): 625-638 (2019).
[cited by applicant]
Leonard, J. P et al., “AUGMENT: A Phase III Study of Lenalidomide Plus Rituximab Versus Placebo Plus Rituximab in Relapsed or Refractory Indolent Lymphoma,” J Clin Oncol., vol. 37(14):1188-99 (2019).
[cited by applicant]
Locke, F et al., “Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): a single-arm, multicentre, phase 1-2 trial,” Lancet Oncol., vol. 20(1):31-42 (2019).
[cited by applicant]
Lum and Thakur, “Targeting T cells with bispecific antibodies for cancer therapy,” BioDrugs, vol. 25(6): 365-379 (2011).
[cited by applicant]
Mau-Soerensen, M. et al. “A phase I trial of intravenous catumaxomab: a bispecific monoclonal antibody targeting EpCAM and the T cell coreceptor CD,” Cancer Chemother. Pharmacol., vol. 75(5): 1065-1073 (2015).
[cited by applicant]
MedlinePlus. Lenalidomide, Mar. 22, 2022 pp. 1-7 (2022).
[cited by applicant]
Mendez MJ, et al., “Functional transplant of megabase human immunoglobulin loci recapitulates human antibody response in mice,” Nat Genet., vol. 15(2):146-56 (1997).
[cited by applicant]
Mølhøj M, et al., “CD19-/CD3-bispecific antibody of the BiTE class is far superior to tandem diabody with respect to redirected tumor cell lysis,” Mol Immunol., vol. 44(8):1935-43 (2007).
[cited by applicant]
Mounier, N. et al., “Rituximab plus gemcitabine and oxaliplatin in patients with refractory/relapsed diffuse large B-cell lymphoma who are not candidates for high-dose therapy. A phase II Lymphoma Study Association tria…
[cited by applicant]
Mounier, N., “Rituximab plus CHOP (R-CHOP) overcomes bcl-2—associated resistance to chemotherapy in elderly patients with diffuse large B-cell lymphoma (DLBCL),” Blood, vol. 101: 4279-4284 (2003).
[cited by applicant]
Myers EW et al., “Optimal alignments in linear space,” Comput Appl Biosci., vol. 4(1):11-17 (1988).
[cited by applicant]
NCT04358458, pp. 1-7, Apr. 20, 2020. (2020).
[cited by applicant]
Needleman and Wunsch, J., “A general method applicable to the search for similarities in the amino acid sequence of two proteins,” Mol. Biol., vol. 48(3): 444-453 (1970).
[cited by applicant]
Neelapu SS, et al., “Chimeric antigen receptor T-cell therapy—assessment and management of toxicities,” Nat Rev Clin Oncol., vol. 15(1):47-62 (2018).
[cited by applicant]
Paino, T. et al., “CD20 positive cells are undetectable in the majority of multiple myeloma cell lines and are not associated with a cancer stem cell phenotype,” Diagnostic Pathology, vol. 6:33 (2011).
[cited by applicant]
Parren PW, et al., “On the interaction of IgG subclasses with the low affinity Fc gamma RIIa (CD32) on human monocytes, neutrophils, and platelets, Analysis of a functional polymorphism to human IgG2,” J Clin Invest., v…
[cited by applicant]
Patrizia, M. et al. “Bendamustine plus Rituximab Versus R-CHOP as First-Line Treatment for Patients with Follicular Lymphoma Grade 3A: Evidence from a Multicenter, Retrospective Study,” The Oncologist, vol. 23(4):454-46…
[cited by applicant]
Paul, W. Fundamental Immunology Ch. 7 ( 2nd ed. Raven Press, N.Y. (1989).
[cited by applicant]
Pearce LA, et al., “Linear gene fusions of antibody fragments with streptavidin can be linked to biotin labelled secondary molecules to form bispecific reagents,” Biochem Mol Biol Int., vol. 42(6):1179-1188 (1997).
[cited by applicant]
Pluckthun in ‘The Pharmacology of Monoclonal Antibodies’, vol. 113, Rosenburg and Moore eds. Springer-Verlag, New York, pp. 269 315 (1994).
[cited by applicant]
Poncelet P, et al., “Cytofluorometric quantification of cell-surface antigens by indirect immunofluorescence using monoclonal antibodies,” J Immunol Methods, vol. 85(1):65-74 (1985).
[cited by applicant]
Prescribing Information for Imbruvica®, Retrieved on May 4, 2023, https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/205552s007lbl.pdf, 32 pages.
[cited by applicant]
Prescribing Information for Polivy®, Retrieved on May 4, 2023, https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/761121s000lbl.pdf, 19 pages.
[cited by applicant]
Project et al., “A predictive model for aggressive non-Hodgkin's lymphoma,” N Engl J Med., vol. 329(14):987-994 (1993) Shipp.
[cited by applicant]
Rasouli M. “Basic concepts and practical equations on osmolality: Biochemical approach,” Clin Biochem., vol. 49(12):936-941 (2016).
[cited by applicant]
Remington: The Science and Practice of Pharmacy, 19th Edition, Gennaro, Ed., Mack Publishing Co., Easton, PA, 1995.
[cited by applicant]
Revets H, et al., “Nanobodies as novel agents for cancer therapy,” Expert Opin Biol Ther., vol. 5(1):111-24 (2005).
[cited by applicant]
Rummel, M. et al., Lymphoma: Chemotherapy, Excluding Pre-Clinical Models Non-Hodgkin Lymphoma Therapy, Blood, vol. 114 (22) (Abstract No. 405):3 pages (2009).
[cited by applicant]
Sambrook et al., 1989, Molecular Cloning: A laboratory Manual, New York: Cold Spring Harbor Laboratory Press, Ch. 15.
[cited by applicant]
Sarkozy and Sehn, “Management of relapsed/refractory DLBCL,” Best Practice & Research in Clinical Hematology, vol. 31: 209-216 (2018).
[cited by applicant]
Sarkozy, C. et al., “Cause of Death in Follicular Lymphoma in the First Decade of the Rituximab Era: A Pooled Analysis of French and US Cohorts,” J Clin Oncol., vol. 37:144-152. (2018).
[cited by applicant]
Schakowski F, et al., “A novel minimal-size vector (MIDGE) improves transgene expression in colon carcinoma cells and avoids transfection of undesired DNA,” Mol Ther., vol. 3(5 Pt 1):793-800 (2001).
[cited by applicant]
Schoonjans R, et al., “Fab chains as an efficient heterodimerization scaffold for the production of recombinant bispecific and trispecific antibody derivatives,” J Immunol., vol. 165(12):7050-7 (2000).
[cited by applicant]
Seiler and Hiddemann, “Advances in the management of follicular lymphoma,” Current Opinion in Oncology, vol. 24(6): 742-747 (2012).
[cited by applicant]
Sykes KF, et al., “Linear expression elements: a rapid, in vivo, method to screen for gene functions,” Nat Biotechnol., vol. 17(4):355-9 (1999).
[cited by applicant]
Tessoulin, B. et al., “Carboplatin instead of cisplatin in combination with dexamethasone, high-dose cytarabine with or without rituximab (DHAC+/−R) is an effective treatment with low toxicity in Hodgkin's and non-Hodgk…
[cited by applicant]
The EMA Guideline on the Evaluation of Anti-cancer Medicinal Products in Man (EMA, 2012).
[cited by applicant]
The EMA Guideline on the Evaluation of Anti-cancer Medicinal Products in Man (EMA, 2017).
[cited by applicant]
Thieblemont, C. et al., “Epcoritamab, a Novel, Subcutaneous CD3xCD20 Bispecific T-Cell-Engaging Antibody, in Relapsed or Refractory Large B-Cell Lymphoma: Dose Expansion in a Phase I/II Trial,” Clinical Oncology, vol. 4…
[cited by applicant]
U.S. Department of Health and Human Services, FDA, Center for Drug Evaluation and Research (CDER), Jul. 2005, pp. i-iii and 1-27. (2005).
[cited by applicant]
Van Heeke G, et al. “Expression of human asparagine synthetase in
[cited by applicant]
Wang, W. et al., “Antibody Structure, Instability, and Formulation,” J Pharm Sci., vol. 96(1)1-26 (2007).
[cited by applicant]
Ward, E. et al. “Binding activities of a repertoire of single immunoglobulin variable domains secreted from
[cited by applicant]
Webster DM, et al., “Engineering antibody affinity and specificity,” Int J Cancer Suppl., vol. 3:13-6 (1988).
[cited by applicant]
Wigler M., et al. “Biochemical transfer of single-copy eucaryotic genes using total cellular DNA as donor,” Cell, vol. 14(3):725-31 (1978).
[cited by applicant]
Wranik BJ et al., “LUZ-Y, a novel platform for the mammalian cell production of full-length IgG-bispecific antibodies,” J Biol Chem., vol. 287(52):43331-9 (2012).
[cited by applicant]
Wu et al., Generation and Characterization of a Dual Variable Domain Immunoglobulin (DVD-Ig™) Molecule, In: Antibody Engineering, Springer Berlin Heidelberg (2010).
[cited by applicant]
Zalevsky J, et al., “Enhanced antibody half-life improves in vivo activity,” Nat Biotechnol., vol. 28(2):157-9 (2010).
[cited by applicant]
Zheng, L., et al., “Expression Improvement and Mechanistic Study of the Retro-Diels-Alderase Catalytic Antibody 10F11 by Site-directed Mutagenesis,” Journal of Molecular Biology, vol. 341(3), 807-14 (2004).
[cited by applicant]
Zhu X. et al., “COMBODY: one-domain antibody multimer with improved avidity,” Immunol Cell Biol., vol. 88(6):667-75 (2010).
[cited by applicant]
Jabbour, E. et al., “Phase II Study Of The Hyper-CVAD Regimen In Combination With Ofatumumab As Frontline Therapy For Adults With CD-20 Positive Acute Lymphoblastic Leukemia (ALL),” Blood, vol. 122(21):2664: 3 pages (20…
[cited by applicant]
Kontermann R., “Dual targeting strategies with bispecific antibodies” mAbs vol. 4(2):182-197 (2012).
[cited by applicant]
Labrijn et al, “Controlled fab-arm exchange for the generation of stable bispecific IgG1,” Nature Protocols, vol. 9 (10): 2450-2463 (2014).
[cited by applicant]
Labrijn et al., “Efficient generation of stable bispecific IgG1 by controlled Fab-arm exchange,” Proc Natl Acad Sci., vol. 110(13):5145-5150 (2013).
[cited by applicant]
Le Tourneau et al., “Dose escalation methods in phase I cancer clinical trials,” Clinical Trials, J Natl Cancer Inst, vol. 101(10):708-720 (2009).
[cited by applicant]
Li T. et al., “Novel Semi-Mechanistic Model Leveraging Preclinical and Clinical Data to Inform the Recommended Phase 2 Dose (RP2D) Selection for Epcoritamab (DuoBody CD3xCD20)”, Nov. 5, 2020 (Nov. 5, 2020), pp. 1-3, Ret…
[cited by applicant]
Lugtenburg P., et al., “First-in-Human, Phase 1/2 Trial to Assess the Safety and Clinical Activity of Subcutaneous GEN3O13 (DuoBody-CD3xCD2O) in B-Cell Non-Hodgkin Lymphomas,” Blood, American Society of Hematology, US, …
[cited by applicant]
Oganesyan, V et al., “Structural characterization of a human Fc fragment engineered for lack of effector functions,” Acta. Cryst., D64, 700-704 (2008).
[cited by applicant]
Overdijk, M et al., “Crosstalk between human IgG isotypes and murine effector cells,” J. Immunol., vol. 189(7): 3430-3438 (2012).
[cited by applicant]
Parren, P. et al., “Induction of T-cell proliferation by recombinant mouse and chimeric mouse/human anti-CD3 monoclonal antibodies,” Res Immunol., vol. 142(9): 749-763 (1991).
[cited by applicant]
Prescribing Information for Bendeka Retrieved on Feb. 9, 2022, www.accessdata.fda.gov/drugsatfda_docs/label/2015/208194s000lbl.pdf. 23 pages.
[cited by applicant]
Prescribing Information for Revlimid, Retrieved on Feb. 9, 2022, www.accessdata.fda.gov/drugsatfda_docs/label/2013/021880s034lbl.pdf, 33 pages.
[cited by applicant]
Schuster, S et al., “Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma,” N Engl J Med, vol. 380(1): 45-56 (2019).
[cited by applicant]
Shields, Robert L. et al., “High Resolution Mapping of the Binding Site on Human IgG1 for FcyRI, FcyRII, FcyRIII, and FcRn and Design of IgG1 Variants with Improved Binding to the FcyR,” The Journal of Biological Chemis…
[cited by applicant]
Stanglmaier, M et al., “Bi20 (fBTA05), a novel trifunctional bispecific antibody (anti-CD20 x anti-CD3), mediates efficient killing of B-cell lymphoma cells even with very low CD20 expression levels,” Int. J. Cancer, vo…
[cited by applicant]
Sun, L et al., “Anti-CD20/CD3 T cell-dependent bispecific antibody; for the treatment of B cell malignancies,” Science Transl Medicine, vol. 7(287): 1-11 (2015).
[cited by applicant]
Tedder, T. et al., “The B cell surface molecule B1 is functionally linked with B cell activation and differentiation,” J. Immunol., vol. 135(2):973-979 (1985).
[cited by applicant]
Valentine, M. et al., “Phosphorylation of the CD20 phosphoprotein in resting B lymphocytes. Regulation by protein kinase C,” J. Biol. Chem., vol. 264(19):11282-11287 (1989).
[cited by applicant]
Van der Neut-Kolfschoten, M. et al., “Anti-inflammatory activity of human IgG4 antibodies by dynamic Fab arm exchange,” Science, vol. 317(5844):1554-1557 (2007).
[cited by applicant]
Wu, C. et al., “Simultaneous targeting of multiple disease mediators by a dual-variable-domain immunoglobulin,” Nat Biotechnol., vol. 25(11): 1290-1297 (2007).
[cited by applicant]
Xu, D. et al., “In vitro characterization of five humanized OKT3 effector function variant antibodies,” Cell Immunol., vol. 200(1):16-26 (2000).
[cited by applicant]
Alvaro-Naranjo, T. et al., “CD20-negative DLBCL transformation after rituximab treatment in follicular lymphoma: a new case report and review of the literature,” Ann Hematol., vol. 82:585-588 (2003).
[cited by applicant]
ASCO Post Staff, “Will Bispecific Antibodies Compete With CAR T-Cell Therapy in Lymphoma?,” pp. 1-5 (2020).
[cited by applicant]
Ausubel, F. et al., ed. Current Protocols in Molecular Biology, Greene Publishing and Wiley InterScience New York (1987).
[cited by applicant]
Bargou, R. et al., “Tumor Regression in Cancer Patients by Very Low Doses of a I Cell-Engaging Antibody,” Science, vol. 321:974-977 (2008).
[cited by applicant]
Bebbington, C.R. et al., “High-level expression of a recombinant antibody from myeloma cells using a glutamine synthetase gene as an amplifiable selectable marker,” Biotechnology, vol. 10(2):169-75 (1992).
[cited by applicant]
Bird, R.E. et al., “Single-chain antigen-binding proteins,” Science, vol. 242(4877):423?426 (1988).
[cited by applicant]
Blankenship JW, et al., “Abstract #5465: CD79BxDR ScorpionTM molecule: a single chain, bispecific Immunotherapeutic with potent in vitro activity against B cell lymphoma ,” AACR 100th Annual Meeting, Cancer Res/, vol. 6…
[cited by applicant]
Blinatumomab prescribing information and medication guide, Dec. 2014, pp. 1-20 and 1-4 (2014).
[cited by applicant]
Bostrom, J. et al., “Variants of the antibody herceptin that interact with HER2 and VEGF at the antigen binding site,” Science, vol. 323 (5921): 1610-1614 (2009).
[cited by applicant]
Brochet X., “IMGT/V-QUEST: the highly customized and integrated system for IG and TR standardized V-J and V-D-J sequence analysis,” Nucl Acids Res., vol. 36:W503-508 (2008).
[cited by applicant]
Brok, H. et al., “An Extensive Monoclonal Antibody Panel for the Phenotyping of Leukocyte Subsets in the Common Marmoset and the Cotton-Top Tamarin,” Cytometry, vol. 45:294-303 (2001).
[cited by applicant]
Bruhns, P. et al., “Specificity and affinity of human Fcgamma receptors and their polymorphic variants for human IgG subclasses,” Blood, vol. 113(16): 3716-3725 (2009).
[cited by applicant]
Buckner , C. et al., “Priming B cell-mediated anti-HIV envelope responses by vaccination allows for the long-tem control of infection in macaques exposed to a R5-tropic SHIN,” Virology, vol. 320, 167-180 (2004).
[cited by applicant]
Chavez, J. et al., “CAR T cell therapy for B-cell lymphomas,” Best Pract Res Clin Haematol., vol. 31(2):135-146 (2018).
[cited by applicant]
Chiu, H. et al., “Combination lenalidomide-rituximab immunotherapy activates anti-tumour immunity and induces tumour cell death by complementary mechanisms of action in follicular lymphoma,” British Journal of Haematolo…
[cited by applicant]
Chothia and Lesk J., “Canonical structures for the hypervariable regions of immunoglobulins,” Mol. Biol., vol. 196(4): 901-917 (1987).
[cited by applicant]
Coraro and Pearson, “Enhancing the efficiency of DNA-mediated gene transfer in mammalian cells,” Somatic Cell Genetics, vol. 7(5):603-615 (1981).
[cited by applicant]
Dall'Acqua, W. et al., “Properties of human IgG1s engineered for enhanced binding to the neonatal Fc receptor (FcRn),” J. Biol. Chem., vol. 281(33):23514-23524 (2006).
[cited by applicant]
Deo YM, et al. “Bispecific molecules directed to the Fc receptor for IgA (Fc alpha RI, CD89) and tumor antigens efficiently promote cell-mediated cytotoxicity of tumor targets in whole blood,” J Immunol., vol. 160(4):16…
[cited by applicant]
Dick LW et al., “C-terminal lysine variants in fully human monoclonal antibodies: investigation of test methods and possible causes,” Biotechnol Bioeng., vol. 100(6):1132-43 (2008).
[cited by applicant]
Dimasi, N., et al., “The design and characterization of oligospecific antibodies for simultaneous targeting of multiple disease mediators,” J Mol Biol., vol. 393(3): 672-92 (2009).
[cited by applicant]
Doppalapudi VR, et al., “Chemically programmed antibodies: endothelin receptor targeting CovX-Bodies,” Bioorg Med Chem Lett., vol. 17(2):501-6 (2007).
[cited by applicant]
Edelman GM, et al., “The covalent structure of an entire gammaG immunoglobulin molecule,” Proc Natl Acad Sci., vol. 63(1):78-85 (1969).
[cited by applicant]
Evans MJ, et al., “Rapid expression of an anti-human C5 chimeric Fab utilizing a vector that replicates in COS and 293 cells,” J Immunol Methods, vol. 84(1):123-38(1995).
[cited by applicant]
Friend, P.J. et al., “Phase I study of an engineered aglycosylated humanized CD3 antibody in renal transplant rejection,” Transplantation, vol. 68 (11): 13 pages (1999).
[cited by applicant]