IP Library › Granted Patent US 12,492,261
Granted Patent B2
US 12,492,261 · App. 17/516,794 · Granted Dec 9, 2025

Subcutaneous dosing of anti-CD20/anti-CD3 bispecific antibodies

Inventors: Chi-Chung Li (South San Francisco, CA); Carol Elaine O'Hear (South San Francisco, CA); Hong Wang (South San Francisco, CA); Brendan Christian Bender (South San Francisco, CA); Iraj Hosseini (South San Francisco, CA)
Assignee: Genentech, Inc.
C07K16/2887A61K31/573A61K39/3955A61P35/00A61P35/02C07K16/2809C07K16/2866A61K2039/505A61K2039/545C07K2317/24C07K2317/31
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Quick Facts
Patent No.
US 12,492,261
App. No.
17/516,794
Granted
Dec 9, 2025
Kind
B2
Abstract

The present invention relates to the treatment of subjects having CD20-positive cell proliferative disorders (e.g., B cell proliferative disorders, such as non-Hodgkin's lymphomas). More specifically, the invention pertains to the treatment of subjects having a B cell proliferative disorder by subcutaneous administration of an anti-CD20/anti-CD3 bispecific antibody.

Claims (48)

1 . A method of treating a subject having a non-Hodgkin's lymphoma (NHL) comprising subcutaneously administering to the subject mosunetuzumab in a dosing regimen comprising eight dosing cycles, wherein:

(a) the first dosing cycle comprises a first subcutaneous dose (C1D1), a second subcutaneous dose (C1D2), and a third subcutaneous dose (C1D3) of mosunetuzumab, wherein:

(i) the C1D1 is 5 mg;

(ii) the C1D2 is 45 mg; and

(iii) the C1D3 is 45 mg; and

(b) the second to eighth dosing cycles each comprises a single subcutaneous dose (C2D1-C8D1) of mosunetuzumab, wherein each of the C2D1-C8D1 of mosunetuzumab is 45 mg,

wherein the eight cycles are 21-day dosing cycles; or the first dosing cycle is a 21-day dosing cycle and the second to eighth dosing cycles are 28-day dosing cycles, and wherein the method comprises administering to the subject the C1D1, the C1D2, and the C1D3 on or about Days 1, 8, and 15, respectively, of the first dosing cycle and administering to the subject the C2D1-C8D1 on Day 1 of each of the second to eighth dosing cycles.

2 . The method of claim 1 , wherein the NHL is a previously untreated (1L) NHL, a relapsed or refractory NHL, a diffuse-large B cell lymphoma (DLBCL), a follicular lymphoma (FL), a mantle cell lymphoma (MCL), a high-grade B cell lymphoma or an Ann Arbor stage III or IV NHL, or a primary mediastinal (thymic) large B cell lymphoma (PMLBCL).

3 . The method of claim 2 , wherein the DLBCL is a Richter's transformation.

4 . The method of claim 2 , wherein the FL is a transformed FL.

5 . The method of claim 1 , wherein the subject had previously been administered at least one prior line of systemic therapy.

6 . The method of claim 5 , wherein at least one prior line of systemic therapy comprised an anti-CD20 antibody or a Bruton's tyrosine kinase (BTK) inhibitor.

7 . The method of claim 6 , wherein the prior line of systemic therapy comprising the anti-CD20 antibody additionally comprises an alkylating agent, vincristine, fludarabine, or an anthracycline.

8 . The method of claim 1 , wherein the dosing regimen comprises one or more additional dosing cycles.

9 . The method of claim 8 , wherein each additional dosing cycle is a 21-day dosing cycle or a 28-day dosing cycle.

10 . The method of claim 8 , wherein each additional dosing cycle comprises administration of an additional dose of mosunetuzumab.

11 . The method of claim 10 , wherein each additional dose of mosunetuzumab is 45 mg.

12 . The method of claim 10 , wherein the method comprises administering to the subject each additional dose of mosunetuzumab on Day 1 of each respective additional dosing cycle.

13 . The method of claim 1 , wherein mosunetuzumab is administered to the subject as a monotherapy or as a combination therapy.

14 . The method of claim 1 , wherein mosunetuzumab is administered to the subject concurrently with an additional therapeutic agent, prior to the administration of an additional therapeutic agent, or subsequent to the administration of one or more additional therapeutic agent.

15 . The method of claim 14 , wherein the additional therapeutic agent is obinutuzumab or tocilizumab.

16 . The method of claim 1 , wherein the subject has a cytokine release syndrome event, and the method further comprises treating the symptoms of the cytokine release syndrome event while suspending treatment with mosunetuzumab.

17 . The method of claim 16 , wherein the method further comprising administering to the subject an effective amount of tocilizumab and/or an effective amount of a corticosteroid to treat the cytokine release syndrome event.

18 . The method of claim 1 , wherein the subject is a human.

19 . The method of claim 8 , wherein the dosing regimen comprises one to nine additional dosing cycles.

20 . The method of claim 19 , wherein each additional dosing cycle is a 21-day dosing cycle.

21 . The method of claim 20 , wherein each additional dosing cycle comprises administration of an additional dose of mosunetuzumab.

22 . The method of claim 21 , wherein each additional dose of mosunetuzumab is 45 mg.

23 . The method of claim 21 , wherein the method comprises administering to the subject each additional dose of mosunetuzumab on Day 1 of each respective additional dosing cycle.

24 . The method of claim 1 , wherein the dosing regimen comprises one to nine additional dosing cycles, wherein each additional dosing cycle is a 21-day dosing cycle, and wherein each additional dosing cycle comprises administration of an additional dose of 45 mg of mosunetuzumab on Day 1 of each respective additional dosing cycle.

25 . The method of claim 19 , wherein each additional dosing cycle is a 28-day dosing cycle.

26 . The method of claim 25 , wherein each additional dosing cycle comprises administration of an additional dose of mosunetuzumab.

27 . The method of claim 26 , wherein each additional dose of mosunetuzumab is 45 mg.

28 . The method of claim 26 , wherein the method comprises administering to the subject each additional dose of mosunetuzumab on Day 1 of each respective additional dosing cycle.

29 . The method of claim 1 , wherein the dosing regimen comprises one to nine additional dosing cycles, wherein each additional dosing cycle is a 28-day dosing cycle, and wherein each additional dosing cycle comprises administration of an additional dose of 45 mg of mosunetuzumab on Day 1 of each respective additional dosing cycle.

30 . The method of claim 8 , wherein the dosing regimen comprises nine additional dosing cycles.

31 . The method of claim 30 , wherein each additional dosing cycle is a 21-day dosing cycle.

32 . The method of claim 31 , wherein each additional dosing cycle comprises administration of an additional dose of mosunetuzumab.

33 . The method of claim 32 , wherein each additional dose of mosunetuzumab is 45 mg.

34 . The method of claim 32 , wherein the method comprises administering to the subject each additional dose of mosunetuzumab on Day 1 of each respective additional dosing cycle.

35 . The method of claim 30 , wherein each additional dosing cycle is a 28-day dosing cycle.

36 . The method of claim 35 , wherein each additional dosing cycle comprises administration of an additional dose of mosunetuzumab.

37 . The method of claim 36 , wherein each additional dose of mosunetuzumab is 45 mg.

38 . The method of claim 36 , wherein the method comprises administering to the subject each additional dose of mosunetuzumab on Day 1 of each respective additional dosing cycle.

39 . The method of claim 1 , wherein the eight cycles are 21-day dosing cycles.

40 . The method of claim 39 , wherein the dosing regimen comprises nine additional dosing cycles, wherein each additional dosing cycle is a 21-day dosing cycle, and wherein each additional dosing cycle comprises administration of an additional dose of 45 mg of mosunetuzumab on Day 1 of each respective additional dosing cycle.

41 . The method of claim 1 , wherein the first dosing cycle is a 21-day dosing cycle and the second to eighth dosing cycles are 28-day dosing cycles.

42 . The method of claim 41 , wherein the dosing regimen comprises nine additional dosing cycles, wherein each additional dosing cycle is a 28-day dosing cycle, and wherein each additional dosing cycle comprises administration of an additional dose of 45 mg of mosunetuzumab on Day 1 of each respective additional dosing cycle.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 21, 2022
From: LI, CHI-CHUNG; O'HEAR, CAROL ELAINE; WANG, HONG; BENDER, BRENDAN CHRISTIAN; HOSSEINI, IRAJ
To: GENENTECH, INC.
Reel/Frame 060802/0252 →
Continuity (4)
Provisional Application 63273566 · Oct 29, 2021
Provisional Application 63188561 · May 14, 2021
Provisional Application 63109777 · Nov 4, 2020
Related Publication 20220153858A1 · May 19, 2022
References Cited (391)
US 5500362A · Robinson et al. · 1996 [cited by applicant]
US 5595756A · Bally et al. · 1997 [cited by applicant]
US 5624821A · Winter et al. · 1997 [cited by applicant]
US 5648260A · Winter et al. · 1997 [cited by applicant]
US 5731168A · Carter et al. · 1998 [cited by applicant]
US 5821337A · Carter et al. · 1998 [cited by applicant]
US 5869046A · Presta et al. · 1999 [cited by applicant]
US 6194551B1 · Idusogie et al. · 2001 [cited by applicant]
US 6248516B1 · Winter et al. · 2001 [cited by applicant]
US 6455043B1 · Grillo-Lopez · 2002 [cited by applicant]
US 6602684B1 · Umana et al. · 2003 [cited by applicant]
US 6737056B1 · Presta · 2004 [cited by applicant]
US 7332581B2 · Presta · 2008 [cited by applicant]
US 7371826B2 · Presta · 2008 [cited by applicant]
US 7612181B2 · Wu et al. · 2009 [cited by applicant]
US 7682612B1 · White et al. · 2010 [cited by applicant]
US 7695936B2 · Carter et al. · 2010 [cited by applicant]
US 7799900B2 · Adams et al. · 2010 [cited by applicant]
US 8219149B2 · Lafata et al. · 2012 [cited by applicant]
US 8258268B2 · Wu et al. · 2012 [cited by applicant]
US 8562992B2 · Adams et al. · 2013 [cited by applicant]
US 8709421B2 · Heiss et al. · 2014 [cited by applicant]
US 8722859B2 · Miller et al. · 2014 [cited by applicant]
US 8895702B2 · Williams et al. · 2014 [cited by applicant]
US 8969526B2 · Baehner et al. · 2015 [cited by applicant]
US 9011864B2 · Schulz et al. · 2015 [cited by applicant]
US 9017676B2 · Lindhofer · 2015 [cited by applicant]
US 9308257B2 · Sharma, Sr. et al. · 2016 [cited by applicant]
US 9315567B2 · Chang et al. · 2016 [cited by applicant]
US 9493563B2 · Blein et al. · 2016 [cited by applicant]
US 9587021B2 · Huang et al. · 2017 [cited by applicant]
US 9657102B2 · Smith et al. · 2017 [cited by applicant]
US 10000576B1 · Weisser et al. · 2018 [cited by applicant]
US 10105391B2 · Wu et al. · 2018 [cited by applicant]
US 10357571B2 · Williams et al. · 2019 [cited by applicant]
US 10561686B2 · Xiao et al. · 2020 [cited by applicant]
US 11466094B2 · Chu et al. · 2022 [cited by applicant]
US 20020164328A1 · Shinkawa et al. · 2002 [cited by applicant]
US 20030115614A1 · Kanda et al. · 2003 [cited by applicant]
US 20030157108A1 · Presta · 2003 [cited by applicant]
US 20040093621A1 · Shitara et al. · 2004 [cited by applicant]
US 20040109865A1 · Niwa et al. · 2004 [cited by applicant]
US 20040110282A1 · Kanda et al. · 2004 [cited by applicant]
US 20040110704A1 · Yamane et al. · 2004 [cited by applicant]
US 20040132140A1 · Satoh et al. · 2004 [cited by applicant]
US 20050014934A1 · Hinton et al. · 2005 [cited by applicant]
US 20050095243A1 · Chan et al. · 2005 [cited by applicant]
US 20050123546A1 · Umana et al. · 2005 [cited by applicant]
US 20090075279A1 · Frantz et al. · 2009 [cited by applicant]
US 20090252683A1 · Kischel et al. · 2009 [cited by applicant]
US 20090304719A1 · Daugherty et al. · 2009 [cited by applicant]
US 20100015133A1 · Igawa et al. · 2010 [cited by applicant]
US 20100150918A1 · Kufer et al. · 2010 [cited by applicant]
US 20100331527A1 · Davis et al. · 2010 [cited by applicant]
US 20110020322A1 · Wilkins et al. · 2011 [cited by applicant]
US 20110123532A1 · Gurney et al. · 2011 [cited by applicant]
US 20110178279A1 · Williams et al. · 2011 [cited by applicant]
US 20120244577A1 · Dixit et al. · 2012 [cited by applicant]
US 20120251531A1 · Baehner et al. · 2012 [cited by applicant]
US 20130129723A1 · Blankenship et al. · 2013 [cited by applicant]
US 20130165638A1 · Hsu et al. · 2013 [cited by applicant]
US 20130171095A1 · Bernett et al. · 2013 [cited by applicant]
US 20130266568A1 · Brinkmann et al. · 2013 [cited by applicant]
US 20130287774A1 · Zugmaier et al. · 2013 [cited by applicant]
US 20140079689A1 · Elliott et al. · 2014 [cited by applicant]
US 20140088295A1 · Smith et al. · 2014 [cited by applicant]
US 20140112914A1 · Nezu et al. · 2014 [cited by applicant]
US 20140170149A1 · Neijssen et al. · 2014 [cited by applicant]
US 20140187753A1 · Blein et al. · 2014 [cited by applicant]
US 20140302064A1 · Moore · 2014 [cited by applicant]
US 20140377270A1 · Moore et al. · 2014 [cited by applicant]
US 20150098900A1 · Ebens et al. · 2015 [cited by applicant]
US 20150133640A1 · Blein et al. · 2015 [cited by applicant]
US 20150166661A1 · Chen et al. · 2015 [cited by applicant]
US 20150266966A1 · Smith et al. · 2015 [cited by applicant]
US 20150284475A1 · Zhou et al. · 2015 [cited by applicant]
US 20160000916A1 · Crotts et al. · 2016 [cited by applicant]
US 20160017058A1 · Kim et al. · 2016 [cited by applicant]
US 20160075785A1 · Ast et al. · 2016 [cited by applicant]
US 20160090416A1 · Gunde et al. · 2016 [cited by applicant]
US 20160145339A1 · Zhou et al. · 2016 [cited by applicant]
US 20160152711A1 · Williams et al. · 2016 [cited by applicant]
US 20160159906A1 · Sun et al. · 2016 [cited by applicant]
US 20160194399A1 · Irving et al. · 2016 [cited by applicant]
US 20160368985A1 · Hotzel et al. · 2016 [cited by applicant]
US 20160368994A1 · Kelley et al. · 2016 [cited by applicant]
US 20170008971A1 · Dennis et al. · 2017 [cited by applicant]
US 20170022274A1 · Chang et al. · 2017 [cited by applicant]
US 20170158773A1 · Adams et al. · 2017 [cited by applicant]
US 20170204194A1 · Chen et al. · 2017 [cited by applicant]
US 20170209573A1 · Bacac et al. · 2017 [cited by applicant]
US 20170218074A1 · Williams et al. · 2017 [cited by applicant]
US 20170224818A1 · Lindhofer et al. · 2017 [cited by applicant]
US 20170267783A1 · Nezu et al. · 2017 [cited by applicant]
US 20180057593A1 · Dennis · 2018 [cited by applicant]
US 20180134798A1 · Chu · 2018 [cited by examiner]
US 20180148508A1 · Wang et al. · 2018 [cited by applicant]
US 20180193479A1 · Williams et al. · 2018 [cited by applicant]
US 20200129617A1 · Brownstein et al. · 2020 [cited by applicant]
US 20200164077A1 · Williams et al. · 2020 [cited by applicant]
US 20200199578A1 · Short et al. · 2020 [cited by applicant]
US 20200308309A1 · Bardroff · 2020 [cited by examiner]
US 20200339686A1 · Sato et al. · 2020 [cited by applicant]
CN 102281902A · 2011 [cited by applicant]
CN 102369218A · 2012 [cited by applicant]
CN 103025759A · 2013 [cited by applicant]
CN 101675077B · 2013 [cited by applicant]
CN 104321081A · 2015 [cited by applicant]
CN 106029696A · 2016 [cited by applicant]
EP 1870459A1 · 2007 [cited by applicant]
EP 1923072A1 · 2008 [cited by applicant]
EP 1870459A4 · 2010 [cited by applicant]
EP 2482212A1 · 2012 [cited by applicant]
EP 2578230A1 · 2013 [cited by applicant]
EP 2647707A1 · 2013 [cited by applicant]
EP 2647707A4 · 2014 [cited by applicant]
EP 2769989A1 · 2014 [cited by applicant]
EP 2840091A1 · 2015 [cited by applicant]
EP 1870459B1 · 2016 [cited by applicant]
JP 2008291036A · 2008 [cited by applicant]
JP 2009539413A · 2009 [cited by applicant]
JP 2013515509A · 2013 [cited by applicant]
JP 2013528569A · 2013 [cited by applicant]
JP 2013529084A · 2013 [cited by applicant]
JP 2015509951A · 2015 [cited by applicant]
JP 2015509952A · 2015 [cited by applicant]
JP 2018527887A · 2018 [cited by applicant]
KR 1020160098464A · 2016 [cited by applicant]
RU 2539112C2 · 2015 [cited by applicant]
TW 201508008A · 2015 [cited by applicant]
TW 201827075A · 2018 [cited by applicant]
WO WO9103493A1 · 1991 [cited by applicant]
WO WO9222653A1 · 1992 [cited by applicant]
WO WO9404679A1 · 1994 [cited by applicant]
WO WO9429351A2 · 1994 [cited by applicant]
WO WO9601126A1 · 1996 [cited by applicant]
WO WO9627011A1 · 1996 [cited by applicant]
WO WO9730087A1 · 1997 [cited by applicant]
WO WO9850431A2 · 1998 [cited by applicant]
WO WO9858964A1 · 1998 [cited by applicant]
WO WO9850431A3 · 1999 [cited by applicant]
WO WO9922764A1 · 1999 [cited by applicant]
WO WO9951642A1 · 1999 [cited by applicant]
WO WO0061739A1 · 2000 [cited by applicant]
WO WO0129246A1 · 2001 [cited by applicant]
WO WO0231140A1 · 2002 [cited by applicant]
WO WO03011878A2 · 2003 [cited by applicant]
WO WO03084570A1 · 2003 [cited by applicant]
WO WO03085107A1 · 2003 [cited by applicant]
WO WO03085119A1 · 2003 [cited by applicant]
WO WO2004056312A2 · 2004 [cited by applicant]
WO WO2005035586A1 · 2005 [cited by applicant]
WO WO2005035778A1 · 2005 [cited by applicant]
WO WO2005053742A1 · 2005 [cited by applicant]
WO WO2005083431A2 · 2005 [cited by applicant]
WO WO2005100402A1 · 2005 [cited by applicant]
WO WO2006029879A2 · 2006 [cited by applicant]
WO WO2007005874A2 · 2007 [cited by applicant]
WO WO2007042261A2 · 2007 [cited by applicant]
WO WO2007110205A2 · 2007 [cited by applicant]
WO WO2007146968A2 · 2007 [cited by applicant]
WO WO2008077546A1 · 2008 [cited by applicant]
WO WO2008119566A2 · 2008 [cited by applicant]
WO WO2008119567A2 · 2008 [cited by applicant]
WO WO2009070642A1 · 2009 [cited by applicant]
WO WO2009106321A1 · 2009 [cited by applicant]
WO WO2010057109A1 · 2010 [cited by applicant]
WO WO2010077643A1 · 2010 [cited by applicant]
WO WO2010114940A1 · 2010 [cited by applicant]
WO WO2011028945A1 · 2011 [cited by applicant]
WO WO2011028952A1 · 2011 [cited by applicant]
WO WO2011090754A1 · 2011 [cited by applicant]
WO WO2011090762A1 · 2011 [cited by applicant]
WO WO2011121110A1 · 2011 [cited by applicant]
WO WO2011131746A2 · 2011 [cited by applicant]
WO WO2011143545A1 · 2011 [cited by applicant]
WO WO2012025525A1 · 2012 [cited by applicant]
WO WO2012058768A1 · 2012 [cited by applicant]
WO WO2012058768A8 · 2012 [cited by applicant]
WO WO2012073985A1 · 2012 [cited by applicant]
WO WO2012075581A1 · 2012 [cited by applicant]
WO WO2012123949A1 · 2012 [cited by applicant]
WO WO2012143524A2 · 2012 [cited by applicant]
WO WO2012158818A2 · 2012 [cited by applicant]
WO WO2012162067A2 · 2012 [cited by applicant]
WO WO2013026831A1 · 2013 [cited by applicant]
WO WO2013128027A1 · 2013 [cited by applicant]
WO WO2013128194A1 · 2013 [cited by applicant]
WO WO2014022540A1 · 2014 [cited by applicant]
WO WO2014028560A2 · 2014 [cited by applicant]
WO WO2014047231A1 · 2014 [cited by applicant]
WO WO2014028560A3 · 2014 [cited by applicant]
WO WO2014083178A1 · 2014 [cited by applicant]
WO WO2014108483A1 · 2014 [cited by applicant]
WO WO2014122251A2 · 2014 [cited by applicant]
WO WO2014141152A2 · 2014 [cited by applicant]
WO WO2014144722A2 · 2014 [cited by applicant]
WO WO2014153002A1 · 2014 [cited by applicant]
WO WO2014122251A3 · 2014 [cited by applicant]
WO WO2014170063A1 · 2014 [cited by applicant]
WO WO2014141152A3 · 2014 [cited by applicant]
WO WO2014191113A1 · 2014 [cited by applicant]
WO WO2014193973A2 · 2014 [cited by applicant]
WO WO2014210064A1 · 2014 [cited by applicant]
WO WO2015006749A2 · 2015 [cited by applicant]
WO WO2014191113A8 · 2015 [cited by applicant]
WO WO2015095392A1 · 2015 [cited by applicant]
WO WO2015143079A1 · 2015 [cited by applicant]
WO WO2015184203A1 · 2015 [cited by applicant]
WO WO2015184207A1 · 2015 [cited by applicant]
WO WO2016014942A1 · 2016 [cited by applicant]
WO WO2016019969A1 · 2016 [cited by applicant]
WO WO2016020065A1 · 2016 [cited by applicant]
WO WO2016036678A1 · 2016 [cited by applicant]
WO WO2016049214A1 · 2016 [cited by applicant]
WO WO2016081490A1 · 2016 [cited by applicant]
WO WO2016090210A1 · 2016 [cited by applicant]
WO WO2016110576A1 · 2016 [cited by applicant]
WO WO2016179003A1 · 2016 [cited by applicant]
WO WO2016191750A1 · 2016 [cited by applicant]
WO WO2016201300A1 · 2016 [cited by applicant]
WO WO2016204966A1 · 2016 [cited by applicant]
WO WO2016205520A1 · 2016 [cited by applicant]
WO WO2016205531A2 · 2016 [cited by applicant]
WO WO2017132279A1 · 2017 [cited by applicant]
WO WO2018093821A1 · 2018 [cited by applicant]
WO WO2020232169A1 · 2020 [cited by applicant]
WO WO2022098648A2 · 2022 [cited by applicant]
Paul, Fundamental Immunology, 3rd Edition, 1993, pp. 292-295. [cited by examiner]
Rudikoff et al., Proc. Natl. Acad. Sci. USA, 79(6): 1979-1983, Mar. 1982. [cited by examiner]
Pascalis et al., Journal of Immunology, 2002, vol. 169, pp. 3076-3084. [cited by examiner]
Casset et al., Biochemical and Biophysical Research Communications, 2003, vol. 307, pp. 198-205. [cited by examiner]
Holm et al., Molecular Immunology, 2007, vol. 44, pp. 1075-1084. [cited by examiner]
Audino et al., “Polatuzumab Vedotin, an Antibody-Drug Conjugate Targeting CD79b, Is a Highly Active Agent Against Burkitt Lymphoma and Primary Mediastinal B-Cell Lymphoma,” Blood. 134(Supplement 1):3963 (2019) (5 pages). [cited by applicant]
Forero-Torres et al., “Polatuzumab Vedotin Combined with Obinutuzumab, Cyclophosphamide, Doxorubicin, and Prednisone (G-CHP) for Patients with Previously Untreated Diffuse Large B-Cell Lymphoma (DLBCL): Preliminary Resu… [cited by applicant]
Goebeler et al., “Bispecific T-cell Engager (BiTE) Antibody Construct Blinatumomab for the Treatment of Patients With Relapsed/Refractory Non-Hodgkin Lymphoma: Final Results From a Phase I Study,” J Clin Oncol. 34(10):1… [cited by applicant]
Olszewski et al., “401 Single-agent mosunetuzumab is a promising safe and efficacious chemotherapy-free regimen for elderly/unfit patients with previously untreated diffuse large B-cell lymphoma,” 62nd American Society … [cited by applicant]
Engelberts et al., “DuoBody-CD3xCD20 induces potent T-cell-mediated killing of malignant B cells in preclinical models and provides opportunities for subcutaneous dosing,” EBioMedicine 52:102625 (Jan. 2020) (13 pages). [cited by applicant]
Falchi et al., “An Evidence-based Review of Anti-CD20 Antibody-containing Regimens for the Treatment of Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia, Diffuse Large B-cell Lymphoma, or Follicular Lym… [cited by applicant]
Xu et al., “Production of bispecific antibodies in ‘knobs-into-holes’ using a cell-free expression system,” [cited by applicant]
Yuraszeck et al., “A quantitative systems pharmacology (QSP) model to assess the action of blinatumomab in NHL patients (pts),” Journal of Clinical Oncology 34(15_suppl) Abstract e14511 (May 20, 2016) (3 pages). [cited by applicant]
Office Action for Taiwan Patent Application No. 110140852, dated Dec. 14, 2022 (20 pages). [cited by applicant]
Budde et al., “Mosunetuzumab, a Full-Length Bispecific CD20/CD3 Antibody, Displays Clinical Activity in Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma (NHL): Interim Safety and Efficacy Results from a Phase 1 Study,” B… [cited by applicant]
Goebeler et al., “Bispecific T-cell Engager (BiTE) Antibody Construct Blinatumomab for the Treatment of Patients With Relapsed/Refractory Non-Hodgkin Lymphoma: Final Results From a Phase I Study,” J Clin Oncol. 34(10):1… [cited by applicant]
Hernandez et al., “Pharmacodynamic Effects and Immune Correlates of Response to the CD20/CD3 Bispecific Antibody Mosunetuzumab in Relapsed or Refractory Non-Hodgkin Lymphoma,” Blood. 134(Supplement 1):1585 (2019) (4 pag… [cited by applicant]
Hutchings et al., “Dose escalation of subcutaneous epcoritamab in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: an open-label, phase 1/2 study,” Lancet. 398(10306):1157-69 (2021). [cited by applicant]
Li et al., “Exposure-response analyses indicate a promising benefit/risk profile of mosunetuzumab in relapsed and refractory non-Hodgkin lymphoma,” Blood. 134(Supplement 1):1285 (2019) (8 pages). [cited by applicant]
Olszewski et al., “Single-agent mosunetuzumab is a promising safe and efficacious chemotherapy-free regimen for elderly/unfit patients with previously untreated diffuse large B-cell lymphoma,” American Society of Hemato… [cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2021/057676, mailed Mar. 21, 2022 (18 pages). [cited by applicant]
“History of Changes for Study: NCT02500407: A Safety, Efficacy and Pharmacokinetic Study of BTCT4465A (Mosunetuzumab) as a Single Agent and Combined With Atezolizumab in Non-Hodgkin's Lymphoma (NHL) and Chronic Lymphocy… [cited by applicant]
Auerbach et al., “Angiogenesis assays: problems and pitfalls,” Cancer Metastasis Rev. 19(1-2):167-72 (2000). [cited by applicant]
Bartlett et al., “610 Mosunetuzumab Monotherapy Demonstrates Durable Efficacy with a Manageable Safety Profile in Patients with Relapsed/Refractory Follicular Lymphoma Who Received greater than or equal to 2 Prior Thera… [cited by applicant]
Beans, Carolyn, “Targeting metastasis to halt cancer's spread,” PNAS. 115(50):12539-43 (Dec. 11, 2018). [cited by applicant]
Choi et al, “Reference values of hematology, biochemistry, and blood type in cynomolgus monkeys from cambodia origin,” Lab Anim Res. 32(1):46-55 (Mar. 2016). [cited by applicant]
Curigliano et al., “Safety and Tolerability of Phosphatidylinositol-3-Kinase (PI3K) Inhibitors in Oncology,” Drug Safety. 42:247-62 (Jan. 16, 2019). [cited by applicant]
Dornan et al., “Therapeutic potential of an anti-CD79b antibody-drug conjugate, anti-CD79b-vc-MMAE, for the treatment of non-Hodgkin lymphoma,” Blood. 114(13):2721-9 (2009). [cited by applicant]
Gravanis et al., “The changing world of cancer drug development: the regulatory bodies' perspective,” Chin Clin Oncol. 3(2):22 (2014) (5 pages). [cited by applicant]
Gura, “Systems for identifying new drugs are often faulty,” Science. 278(5340):1041-2 (1997). [cited by applicant]
Hait, William, “Anticancer drug development: the grand challenges,” Nature Reviews/Drug Discovery. 9(4):253-4 (2010). [cited by applicant]
Harris et al., “The World Health Organization Classification of Neoplasms of the Hematopoietic and Lymphoid Tissues: Report of the Clinical Advisory Committee Meeting—Airlie House, Virginia, Nov. 1997,” The Hematology J… [cited by applicant]
Heppner et al., “Tumor heterogeneity: biological implications and therapeutic consequences,” Cancer Metastasis Reviews. 2(1):5-23 (1983). [cited by applicant]
Jain, “Barriers to drug delivery in solid tumors,” Sci Am. 271(1):58-65 (1994). [cited by applicant]
Olszewski et al., “Mosunetuzumab and Polatuzumab Vedotin Demonstrates Preliminary Efficacy in Elderly Unfit/Frail Patients with Previously Untreated Diffuse Large B-Cell Lymphoma,” Blood, 142 (Supplement 1), 855-858 (20… [cited by applicant]
Shao et al., “Distinguishing Hairy Cell Leukemia Variant from Hairy Cell Leukemia: Development and Validation of Diagnostic Criteria,” available in PMC Aug. 30, 2017, published in final edited form as: Leuk Res. 37(4):4… [cited by applicant]
Sporn et al., “Chemoprevention of cancer,” Carcinogenesis. 21(3):525-30 (2000). [cited by applicant]
Wang, et al., “Fixed Duration Mosunetuzumab Plus Polatuzumab Vedotin Has Promising Efficacy and a Manageable Safety Profile in Patients with BTKi Relapsed/Refractory Mantle Cell Lymphoma: Initial Results from a Phase Ib… [cited by applicant]
International Preliminary Report on Patentability for International Patent Application No. PCT/US2021/057676, dated May 8, 2023 (8 pages). [cited by applicant]
“Purified Mouse Anti-Human CD3-epsilon Clone SP34,” BD Biosciences, <https://www.bdbiosciences.com/us/reagents/research/antibodies-buffers/immunology-reagents/anti-non-human-primate-antibodies/cell-surface-antigens/puri… [cited by applicant]
Anderson et al., “G19.4(alpha CD3) x B43(alpha CD19) monoclonal antibody heteroconjugate triggers CD19 antigen-specific lysis of t(4;11) acute lymphoblastic leukemia cells by activated CD3 antigen-positive cytotoxic T c… [cited by applicant]
Atwell et al., “Stable heterodimers from remodeling the domain interface of a homodimer using a phage display library,” J Mol Biol. 270(1):26-35 (1997). [cited by applicant]
Baeuerle et al., “Bispecific T-cell engaging antibodies for cancer therapy,” Cancer Res. 69(12):4941-4 (2009). [cited by applicant]
Bortoletto et al., “Optimizing anti-CD3 affinity for effective T cell targeting against tumor cells,” Eur J Immunol. 32(11):3102-7 (2002). [cited by applicant]
Brack et al., “A Bispecific HER2-Targeting FynomAb with Superior Antitumor Activity and Novel Mode of Action,” Mol Cancer Ther. 13(8):2030-39 (2014) (11 pages). [cited by applicant]
Brinkmann et al., “The making of bispecific antibodies,” MAbs. 9(2):182-212 (2017). [cited by applicant]
Brown et al., “Tolerance to single, but not multiple, amino acid replacements in antibody V [cited by applicant]
Brüggemann et al., “Comparison of the effector functions of human immunoglobulins using a matched set of chimeric antibodies,” J Exp Med. 166(5):1351-61 (1987). [cited by applicant]
Buhmann et al., “Immunotherapy of recurrent B-cell malignancies after allo-SCT with Bi20 (FBTA05), a trifunctional anti-CD3 x anti-CD20 antibody and donor lymphocyte infusion,” Bone Marrow Transplant. 43(5):383-97 (2009… [cited by applicant]
Buhmann et al., “Immunotherapy with FBTA05 (Bi20), a trifunctional bispecific anti-CD3 x anti-CD20 antibody and donor lymphocyte infusion (DLI) in relapsed or refractory B-cell lymphoma after allogeneic stem cell transp… [cited by applicant]
Carter, “Bispecific human IgG by design,” J Immunol Methods. 248(1-2):7-15 (2001). [cited by applicant]
Choi et al., “Bispecific antibodies engage T cells for antitumor immunotherapy,” Expert Opin Biol Ther. 11(7):843-53 (2011). [cited by applicant]
Chu et al., “Immunotherapy with long-lived anti-CD20 x anti-CD3 bispecific antibodies stimulates potent T cell-mediated killing of human B cell lines and of circuating and lymphoid B cells in monkeys: a potential therap… [cited by applicant]
Clynes et al., “Fc receptors are required in passive and active immunity to melanoma,” Proc Natl Acad Sci U S A. 95(2):652-6 (1998). [cited by applicant]
Cragg et al., “Antibody specificity controls in vivo effector mechanisms of anti-CD20 reagents,” Blood. 103(7):2738-43 (2004). [cited by applicant]
Cragg et al., “Complement-mediated lysis by anti-CD20 mAb correlates with segregation into lipid rafts,” Blood. 101(3):1045-52 (2003). [cited by applicant]
Desnoyers et al., “Tumor-Specific Activation of an EGFR-Targeting Probody Enhances Therapeutic Index,” Sci Transl Med. 5(207):207ra144 (2013) (10 pages). [cited by applicant]
Desnoyers et al., “Tumor-specific activation of an EGFR-targeting probody enhances therapeutic index,” Sci Transl Med. 5(207):207ra144 (2013) (2 pages) (Abstract only). [cited by applicant]
Diefenbach et al., “An individualized risk mitigation approach for safety: experience from the mosunetuzumab (CD20/CD3 bispecific antibody) development program in relation to neurotoxicity risk,” 61st ASH Annual Meeting… [cited by applicant]
Donaldson et al., “Design and development of masked therapeutic antibodies to limit off-target effects: application to anti-EGFR antibodies,” available in PMC Jan. 16, 2013, published in final edited form as: Cancer Bio… [cited by applicant]
Donaldson et al., “Design and development of masked therapeutic antibodies to limit off-target effects: application to anti-EGFR antibodies,” Cancer Biol Ther. 8(22): 2145-50 (2009) (6 pages). [cited by applicant]
Drent et al., “A Rational Strategy for Reducing On-Target Off-Tumor Effects of CD38-Chimeric Antigen Receptors by Affinity Optimization,” Mol Ther. 25(8): 1946-58 (2017). [cited by applicant]
Duncan et al., “The binding site for C1q on IgG,” Nature. 332(6166):738-40 (1988). [cited by applicant]
Edelman et al., “The covalent structure of an entire gammaG immunoglobulin molecule,” Proc Natl Acad Sci U S A. 63(1):78-85 (1969). [cited by applicant]
Erster et al., “Site-specific targeting of antibody activity in vivo mediated by disease-associated proteases,” J Control Release. 161(3): 804-12 (2012) (2 pages) (Abstract only). [cited by applicant]
Gaston et al., “Intracellular delivery of therapeutic antibodies into specific cells using antibody- peptide fusions,” Sci Rep. 9(1): 18688 (2019) (12 pages). [cited by applicant]
Gazzano-Santoro et al., “A non-radioactive complement-dependent cytotoxicity assay for anti- CD20 monoclonal antibody,” J Immunol Methods. 202(2):163-71 (1997). [cited by applicant]
Gonzales et al., “Minimizing the Immunogenicity of Antibodies for Clinical Application,” Tumour Biol. 26(1):31-43 (2005) (1 page) (Abstract only). [cited by applicant]
Guyer et al., “Immunoglobulin binding by mouse intestinal epithelial cell receptors,” J Immunol. 117(2):587-93 (1976). [cited by applicant]
Haile et al., “Soluble CD80 Restores T Cell Activation and Overcomes Tumor Cell Programmed Death Ligand 1-Mediated Immune Suppression,” J Immunol. 191(5):2829-36 (2013) (9 pages). [cited by applicant]
Han et al., “Masked Chimeric Antigen Receptor for Tumor-Specific Activation,” Mol Ther. 25(1):274-84 (2017). [cited by applicant]
Hellström et al., “Antitumor effects of L6, an IgG2a antibody that reacts with most human carcinomas,” Proc Natl Acad Sci U S A. 83(18):7059-63 (1986). [cited by applicant]
Hellström et al., “Strong antitumor activities of IgG3 antibodies to a human melanoma-associated ganglioside,” Proc Natl Acad Sci U S A. 82(5):1499-502 (1985). [cited by applicant]
Holliger et al., “Diabodies': small bivalent and bispecific antibody fragments,” Proc Natl Acad Sci USA. 90(14):6444-8 (1993). [cited by applicant]
Holliger et al., “Specific killing of lymphoma cells by cytotoxic T-cells mediated by a bispecific diabody,” Protein Eng. 9(3):299-305 (1996). [cited by applicant]
Honeychurch et al., “Bispecific Ab therapy of B-cell lymphoma: target cell specificity of antibody derivatives appears critical in determining therapeutic outcome,” Cancer Immunol Immunother. 45(3-4):171-3 (1997). [cited by applicant]
Hosseini et al., “Abstract B043: Systems pharmacology modeling of anti-CD20/CD3 T-cell dependent bispecific antibody and its application to clinical trial design,” Proceedings of the Second CRI-CIMT-EATI-AACR Internatio… [cited by applicant]
Hosseini et al., “Mitigating The Risk Of Cytokine Release Syndrome In A Phase I Trial Of CD20/CD3 Bispecific Antibody Mosunetuzumab In NHL: Impact Of Translational System Modeling,” NPJ Syst Biol Appl. 6(1):28 (2020) (1… [cited by applicant]
Hosseini et al., “Systems pharmacology modeling of anti-CD20/CD3 T-cell dependent bispecific antibody and its application to clinical trial design,” American Conference on Pharmacometrics 7; Oct. 25; Bellevue, WA. (2016… [cited by applicant]
Huang et al., “In Vivo Deamidation Characterization of Monoclonal Antibody by LC/MS/MS,” Anal Chem. 77(5):1432-9 (2005). [cited by applicant]
Huang et al., “Structural chemistry and therapeutic intervention of protein-protein interactions in immune response, human immunodeficiency virus entry, and apoptosis,” Pharmacol Ther. 86(3):201-215 (2000). [cited by applicant]
Hudson et al., “Engineered antibodies,” Nat Med. 9(1):129-34 (2003). [cited by applicant]
Huehls et al., “Bispecific T-cells engagers for cancer immunotherapy,” Immunol Cell Biol. 93(3):290-6 (2015). [cited by applicant]
Idusogie et al., “Mapping of the C1q Binding Site on Rituxan, A Chimeric Antibody with a Human IgG1 Fc,” J Immunol. 164(8):4178-84 (2000). [cited by applicant]
Igawa et al., “VH/VL interface engineering to promote selective expression and inhibit conformational isomerization of thrombopoietin receptor agonist single-chain diabody,” Protein Eng Des Sel. 23(8):667-77 (2010) (11 … [cited by applicant]
Jager et al., “The trifunctional antibody ertumaxomab destroys tumor cells that express low levels of human epidermal growth factor receptor 2,” Cancer Res. 69(10):4270-6 (2009). [cited by applicant]
Junttila et al., “Antitumor Efficacy of a Bispecific Antibody That Targets HER2 and Activates T Cells,” Cancer Res. 74(19):5561-71 (2014). [cited by applicant]
Kanda et al., “Comparison of cell lines for stable production of fucose-negative antibodies with enhanced ADCC,” Biotechnol Bioeng. 94(4):680-8 (2006). [cited by applicant]
Kelley et al., “Thermodynamic Analysis of an Antibody Functional Epitope,” Biochemistry. 32(27):6828-35 (1993). [cited by applicant]
Kiewe et al., “Phase I trial of the trifunctional anti-HER2 x anti-CD3 antibody ertumaxomab in metastatic breast cancer,” 2005 ASCO Annual Meeting Proceedings. J Clin Oncol. 23(16S):Abstract 2530 (2005) (1 page). [cited by applicant]
Kiewe et al., “Phase I trial of the trifunctional anti-HER2 x anti-CD3 antibody ertumaxomab in metastatic breast cancer,” Clin Cancer Res. 12(10):3085-91 (2006). [cited by applicant]
Kim et al., “Localization of the site of the murine IgG1 molecule that is involved in binding to the murine intestinal Fc receptor,” Eur J Immunol. 24(10):2429-34 (1994). [cited by applicant]
Kipriyanov et al., “Bispecific tandem diabody for tumor therapy with improved antigen binding and pharmacokinetics,” J Mol Biol. 293(1):41-56 (1999). [cited by applicant]
Klein et al., “Progress in overcoming the chain association issue in bispecific heterodimeric IgG antibodies,” MAbs. 4(6):653-63 (2012). [cited by applicant]
Kontermann, “Dual targeting strategies with bispecific antibodies,” mAbs. 4(2):182-97 (2012). [cited by applicant]
Kortt et al., “Dimeric and trimeric antibodies: high avidity scFvs for cancer targeting,” Biomol Eng. 18(3):95-108 (2001) (15 pages). [cited by applicant]
Law et al., “Expression and characterization of recombinant soluble human CD3 molecules: presentation of antigenic epitopes defined on the native TCR-CD3 complex” Int Immunol 14(4):389-400 (2002). [cited by applicant]
Leabman et al., “Effects of altered FcγR binding on antibody pharmacokinetics in cynomolgus monkeys,” mAbs. 5(6):896-903 (2013). [cited by applicant]
Lee et al., “Current concepts in the diagnosis and management of cytokine release syndrome,” Blood. 124(2):188-95 (2014) (18 pages). [cited by applicant]
Li et al., “Exposure-response analyses indicate a promising benefit/risk profile of mosunetuzumab in relapsed and refractory non-Hodgkin lymphoma,” 61st ASH Annual Meeting & Exposition, Dec. 7-10, 2019, Orlando, Florida… [cited by applicant]
Li, “Successful QSP modeling in drug development starts with the right questions,” American Conference on Pharmacometrics 8, Oct. 16, Fort Lauderdale, FL. (2017) (20 pages). [cited by applicant]
Lippow et al., “Computational Design of Antibody-Affinity Improvement Beyond in Vivo Maturation,” available in PMC Jan. 7, 2010, published in final edited form as: Nat Biotechnol. 25(10):1171-6 (2007) (14 pages). [cited by applicant]
Liu et al., “Affinity-Tuned ErbB2 or EGFR Chimeric Antigen Receptor T Cells Exhibit an Increased Therapeutic Index against Tumors in Mice,” Cancer Res. 75(17):3596-607 (2015) (13 pages). [cited by applicant]
Liu et al., “Heteroantibody duplexes target cells for lysis by cytotoxic T lymphocytes,” Proc Natl Acad Sci U S A. 82(24):8648-52 (1985). [cited by applicant]
Liu et al., “Improvement in soluble expression levels of a diabody by exchanging expression vectors,” Protein Expr Purif. 62(1): 15-20 (2008) (6 pages). [cited by applicant]
Lord et al., “Structure-based engineering to restore high affinity binding of an isoform-selective anti-TGFß1 antibody,” MAbs. 10(3):444-452 (2018). [cited by applicant]
Lu et al., “Tetravalent anti-CD20/CD3 bispecific antibody for the treatment of B cell lymphoma,” Biochem Biophys Res Commun. 473(4):808-813 (2016) (3 pages) (Abstract only). [cited by applicant]
Lum et al., “Targeting T cells with bispecific antibodies for cancer therapy,” available in PMC Oct. 8, 2013, published in final edited form as: BioDrugs. 25(6):365-79 (2011) (24 pages). [cited by applicant]
Mariuzza et al., “The structural basis of antigen-antibody recognition,” Annu Rev Biophys Biophys Chem. 16:139-159 (1987) (2 pages) (Abstract only). [cited by applicant]
Merchant et al., “An efficient route to human bispecific IgG,” Nat Biotechnol. 16(7):677-81 (1998). [cited by applicant]
Metz et al., “Bispecific antibody derivatives with restricted binding functionalities that are activated by proteolytic processing,” Protein Eng Des Sel. 25(10):571-80 (2012). [cited by applicant]
Milne et al., “Systematic Analysis of Immune Infiltrates in High-Grade Serous Ovarian Cancer Reveals CD20, FoxP3 and TIA-1 as Positive Prognostic Factors,” PLoS One. 4(7):e6412 (2009) (14 pages). [cited by applicant]
Moore et al., “Application of dual affinity retargeting molecules to achieve optimal redirected T-cell killing of B-cell lymphoma,” Blood. 117(17):4542-51 (2011) (11 pages). [cited by applicant]
Nagorsen et al., “Immunomodulatory therapy of cancer with T cell-engaging BiTE antibody blinatumomab,” Exp Cell Res. 317(9):1255-60 (2011). [cited by applicant]
NIH/NCI, “anti-PD-1 fusion protein AMP-224,” dated Jul. 10, 2015, accessed Jul. 31, 2019 (1 page). [cited by applicant]
Nishimoto et al., “Toxicity, pharmacokinetics, and dose-finding study of repetitive treatment with the humanized anti-interleukin 6 receptor antibody MRA in rheumatoid arthritis. Phase I/II clinical study,” J Rheumatol.… [cited by applicant]
Okazaki et al., “Fucose depletion from human IgG1 oligosaccharide enhances binding enthalpy and association rate between IgG1 and FcgammaRIIIa,” J Mol Biol. 336(5):1239-49 (2004). [cited by applicant]
Paino et al., “Reply to ‘Response to “CD20 Positive Cells Are Undetectable in the Majority of Multiple Myeloma Cell Lines and Are Not Associated With a Cancer Stem Cell Phenotype,’”” Haematologica. 97(7):1110-1114 (2012… [cited by applicant]
Pessano et al., “The T3/T cell receptor complex: antigenic distinction between the two 20-kd T3 (T3-δand T3-ε) subunits,” EMBO J. 4(2):337-44 (1985). [cited by applicant]
Petkova et al., “Enhanced half-life of genetically engineered human IgG1 antibodies in a humanized FcRn mouse model: potential application in humorally mediated autoimmune disease,” Int Immunol. 18(12):1759-69 (2006). [cited by applicant]
Polu et al., “Probody therapeutics for targeting antibodies to diseased tissue,” Expert Opin Biol Ther. 14(8):1049-53 (2014). [cited by applicant]
Ravetch et al., “Fc receptors,” Annu Rev Immunol. 9:457-92 (1991). [cited by applicant]
Reusch et al., “A tetravalent bispecific TandAb (CD19/CD3), AFM11, efficiently recruits T cells for the potent lysis of CD19(+) tumor cells,” MAbs. 7(3):584-604 (2015) (22 pages). [cited by applicant]
Reusch et al., “Anti-CD3 x anti-epidermal growth factor receptor (EGFR) bispecific antibody redirects T-cell cytolytic activity to EGFR-positive cancers in vitro and in an animal model,” Clin Cancer Res. 12(1):183-90 (2… [cited by applicant]
Ridgway et al., “‘Knobs-into-holes’ engineering of antibody C [cited by applicant]
Riedle et al., “In vivo activation and expansion of T cells by a bi-specific antibody abolishes metastasis formation of human melanoma cells in SCID mice,” Int J Cancer. 75(6):908-18 (1998). [cited by applicant]
Ripka et al., “Two Chinese hamster ovary glycosylation mutants affected in the conversion of GDP-mannose to GDP-fucose,” Arch Biochem Biophys. 249(2):533-45 (1986). [cited by applicant]
Roosnek et al., “Triggering T Cells by Otherwise Inert Hybrid Anti-CD3/Antitumor Antibodies Requires Encounter with the Specific Target Cell,” J Exp Med. 170(1):297-302 (1989) (6 pages). [cited by applicant]
Salmerón et al., “A conformational epitope expressed upon association of CD3-epsilon with either CD3-delta or CD3-gamma is the main target for recognition by anti-CD3 monoclonal antibodies,” J Immunol. 147(9): 3047-52 (… [cited by applicant]
Saphire et al., “Crystal structure of a neutralizing human IgG against HIV-1: a template for vaccine design,” Science. 293(5532):1155-9 (2001). [cited by applicant]
Schuster et al., “Immunotherapy with the trifunctional anti-CD20 x anti-CD3 antibody FBTA05 (Lymphomun) in paediatric high-risk patients with recurrent CD20-positive B cell malignancies,” Br J Haematol. 169:90-102 (2015… [cited by applicant]
Seimetz et al., “Development and approval of the trifunctional antibody catumaxomab (anti-EpCAM x anti-CD3) as a targeted cancer immunotherapy,” Cancer Treat Rev. 36(6):458-67 (2010). [cited by applicant]
Sen et al., “Use of Anti-CD3 x Anti-HER2/neu Bispecific Antibody for Redirecting Cytotoxicity of Activated T Cells Toward HER2/neu+ Tumors,” J Hematother Stem Cell Res. 10(2):247-60 (2001). [cited by applicant]
Shalaby et al., “Bispecific HER2 x CD3 antibodies enhance T-cell cytotoxicity in vitro and localize to HER2-overexpressing xenografts in nude mice,” Clin Immunol Immunopathol. 74(2):185-92 (1995). [cited by applicant]
Shen et al., “Preparation and characterization for bispecific antibodies of anti-CD3 x anti-idiotype to B cell lymphocytic leukemia,” J Tongji Med Univ. 19(3):166-9 (1999) (4 pages). [cited by applicant]
Shi et al., “Margin-Infiltrating CD20+ B Cells Display an Atypical Memory Phenotype and Correlate with Favorable Prognosis in Hepatocellular Carcinoma,” Clin Cancer Res. 19(21):5994-6005 (2013). [cited by applicant]
Shields et al., “High resolution mapping of the binding site on human IgG1 for FcγRI, FcγRII, FcγRIII, and FcRn and design of IgG1 variants with improved binding to the FcγR,” J Biol Chem. 276(9):6591-604 (2001). [cited by applicant]
Somasundaram et al., “Will Engineered T Cells Expressing CD20 scFv Eradicate Melanoma?” Mol Ther. 19(4):638-40 (2011). [cited by applicant]
Sondermann et al., “The 3.2-A crystal structure of the human IgG1 Fc fragment-FcγRIII complex,” Nature. 406(6793):267-73 (2000). [cited by applicant]
Spiess et al., “Alternative molecular formats and therapeutic applications for bispecific antibodies,” Mol Immunol. 67(2 pt A):95-106 (2015). [cited by applicant]
Spiess et al., “Bispecific antibodies with natural architecture produced by co-culture of bacteria expressing two distinct half-antibodies,” Nat Biotechnol. 31(8):753-8 (2013) (7 pages). [cited by applicant]
Stanglmaier 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. 123(5):… [cited by applicant]
Stein et al., “Novel and Emerging Drugs for Acute Myeloid Leukemia,” available in PMC May 22, 2014, published in final edited form as: Curr Cancer Drug Targets. 12(5):522-530 (2012) (19 pages). [cited by applicant]
Stieglmaier et al., “Utilizing the BiTE (bispecific T-cell engager) platform for immunotherapy of cancer,” Expert Opin Biol Ther. 15(8):1093-9 (2015) (8 pages). [cited by applicant]
Stubenrauch et al., “Impact of molecular processing in the hinge region of therapeutic IgG4 antibodies on disposition profiles in cynomolgus monkeys,” Drug Metab Dispos. 38(1):84-91 (2010). [cited by applicant]
Sun et al., “Anti-CD20/CD3 T cell-dependent bispecific antibody for the treatment of B cell malignancies,” Sci Transl Med. 7(287):287ra70 (2015) (11 pages). [cited by applicant]
Wakefield et al., “Addition of a C-terminal extension sequence to transforming growth factor-beta 1 interferes with biosynthetic processing and abolishes biological activity,” Growth Factors. 5(3):243-53 (1991) (2 pages… [cited by applicant]
Wark et al., “Latest technologies for the enhancement of antibody affinity,” Adv Drug Deliv Rev. 58(5-6):657-70 (2006). [cited by applicant]
Weidle et al., “The Intriguing Options of Multispecific Antibody Formats for Treatment of Cancer,” Cancer Genomics Proteomics. 10(1):1-18 (2013) (18 pages). [cited by applicant]
Wells et al., “Reaching for high-hanging fruit in drug discovery at protein-protein interfaces,” Nature. 450(7172):1001-9 (2007). [cited by applicant]
Westin et al., “Safety and activity of PD1 blockade by pidilizumab in combination with rituximab in patients with relapsed follicular lymphoma: a single group, open-label, phase 2 trial,” Lancet Oncol. 15(1):69-77 (2014… [cited by applicant]
Wright et al., “Effect of glycosylation on antibody function: implications for genetic engineering,” Trends Biotechnol. 15(1):26-32 (1997). [cited by applicant]
Wu et al., “Humanization of a Murine Monoclonal Antibody by Simultaneous Optimization of Framework and CDR Residues,” J Mol Biol. 294(1):151-162 (1999). [cited by applicant]
Wuellner et al., “Bispecific CD3/HER2 Targeting FynomAb Induces Redirected T Cell-Mediated Cytolysis with High Potency and Enhanced Tumor Selectivity,” Antibodies. 4(4):426-440 (2015) (15 pages). [cited by applicant]
Yamane-Ohnuki et al., “Establishment of FUT8 knockout Chinese hamster ovary cells: an ideal host cell line for producing completely defucosylated antibodies with enhanced antibody-dependent cellular cytotoxicity,” Biote… [cited by applicant]
Yan et al., “Succinimide Formation at Asn 55 in the Complementarity Determining Region of a Recombinant Monoclonal Antibody IgG1 Heavy Chain,” J Pharm Sci. 98(10):3509-21 (2009). [cited by applicant]
Yang et al., “Generation and characterization of a target-selectively activated antibody against epidermal growth factor receptor with enhanced anti-tumor potency,” MAbs. 7(2):440-50 (2015). [cited by applicant]
Zhu et al., “Engineering high affinity humanized anti-p185HER2/anti-CD3 bispecific F(ab')2 for efficient lysis of p185HER2 overexpressing tumor cells,” Int J Cancer. 62(3):319-24 (1995). [cited by applicant]
Zhu et al., “Identification of heavy chain residues in a humanized anti-CD3 antibody important for efficient antigen binding and T cell activation,” J Immunol. 155(4):1903-10 (1995). [cited by applicant]
Budde et al., “Single-Agent Mosunetuzumab Shows Durable Complete Responses in Patients with Relapsed or Refractory B-Cell Lymphomas: Phase I Dose-Escalation Study,” J Clin Oncol 40:481-49 (Dec. 2021). [cited by applicant]
Budde et al., “1628 Subcutaneous Mosunetuzumab Is Active with a Manageable Safety Profile in Patients (pts) with Relapsed/Refractory (R/R) B-Cell Non-Hodgkin Lymphomas (B-NHLs): Update Results from a Phase I/II Study,” … [cited by applicant]
Cleveland Clinic, “Non-Hodgkin Lymphoma” https://my.clevelandclinic.org/health/diseases/15662-non-hodgkin-lymphoma; accessed online Jul. 29, 2024. [cited by applicant]
International Nonproprietary Names for Pharmaceutical Substances, WHO Drug Information, vol. 31, No. 2, 2017. [cited by applicant]
Cited By (1)
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