IP Library › Granted Patent US 12,291,575
Granted Patent B2
US 12,291,575 · App. 17/744,262 · Granted May 6, 2025

Methods for treatment of CD20-positive proliferative disorder with mosunetuzumab and polatuzumab vedotin

Inventors: Carol Elaine O'Hear (South San Francisco, CA); Yasuhiro Oki (South San Francisco, CA); Iris Tranthuyngan To (South San Francisco, CA)
Assignee: Genentech, Inc.
C07K16/2887A61P35/00C07K16/2866C07K16/2896A61K2039/507A61K2039/545
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,291,575
App. No.
17/744,262
Granted
May 6, 2025
Kind
B2
Abstract

The present invention relates to the treatment of subjects having a CD20-positive cell proliferative disorder. More specifically, the invention pertains to the treatment of subjects having a CD20-positive cell proliferative disorder by administering a combination of mosunetuzumab and polatuzumab vedotin.

Claims (166)

1. A method of treating a subject having a B cell proliferative disorder comprising subcutaneously administering to the subject mosunetuzumab and intravenously administering to the subject polatuzumab vedotin in a dosing regimen comprising at least a first 21-day dosing cycle and a second 21-day dosing cycle, wherein:

(a) the first dosing cycle comprises a first dose (C1D1) of mosunetuzumab, a second dose (C1D2) of the mosunetuzumab, a third dose (C1D3) of mosunetuzumab, and a first dose (C1D1) of polatuzumab vedotin, wherein the C1D1 of mosunetuzumab is 5 mg, the C1D2 of mosunetuzumab is 15 mg, and the C1D3 of mosunetuzumab is 45 mg, and wherein the C1D1 of polatuzumab vedotin is 1.8 mg/kg; and

(b) the second dosing cycle comprises a single dose (C2D1) of mosunetuzumab and a single dose (C2D1) of polatuzumab vedotin, wherein the C2D1 of mosunetuzumab is 45 mg, and wherein the C2D1 of polatuzumab vedotin is 1.8 mg/kg, and

wherein the C1D1, C1D2, and C1D3 of mosunetuzumab are administered on or about Days 1, 8, and 15, respectively, of the first dosing cycle, the C1D1 of polatuzumab vedotin is administered on Day 1 of the first dosing cycle, the C2D1 of polatuzumab vedotin is administered on Day 1 of the second dosing cycle, and the C1D1 of polatuzumab vedotin is administered prior to administration of the C1D1 of mosunetuzumab.

2. The method of claim 1 , wherein:

(a) wherein the C2D1 of polatuzumab vedotin is administered prior to administration of the C2D1 of mosunetuzumab; and/or

(b) the method further comprises one or more additional dosing cycles.

3. The method of claim 2 , wherein the method comprises six additional dosing cycles.

4. The method of claim 2 , wherein:

(a) each additional dosing cycle is a 21-day dosing cycle; and/or

(b) the one or more of the additional dosing cycles each comprise an additional single dose of mosunetuzumab and an additional single dose of polatuzumab vedotin, or the one or more of the additional dosing cycles each comprise an additional single dose of mosunetuzumab and do not comprise administration of polatuzumab vedotin.

5. The method of claim 4 , wherein:

(a) the additional single dose of polatuzumab vedotin is 1.8 mg/kg;

(b) each additional single dose of polatuzumab vedotin is administered to the subject on Day 1 of each additional dosing cycle comprising an additional dose of polatuzumab vedotin;

(c) the additional single dose of mosunetuzumab is 45 mg; and/or

(d) each additional single dose of mosunetuzumab is administered to the subject on Day 1 of each additional dosing cycle comprising an additional dose of mosunetuzumab.

6. The method of claim 4 , wherein the dosing regimen comprises six additional dosing cycles, wherein each of the six additional dosing cycles comprises a single dose of mosunetuzumab, and wherein no more than four of the six additional dosing cycles comprise administration of polatuzumab vedotin.

7. A method of treating a subject having a B cell proliferative disorder comprising subcutaneously administering to the subject mosunetuzumab and intravenously administering to the subject polatuzumab vedotin in a dosing regimen comprising eight 21-day dosing cycles, wherein:

(a) the first dosing cycle comprises:

(i) a first dose (C1D1) of mosunetuzumab, a second dose (C1D2) of mosunetuzumab, and a third dose (C1D3) of mosunetuzumab, wherein the C1D1 of mosunetuzumab is 5 mg, the C1D2 of mosunetuzumab is 45 mg, and the C1D3 of mosunetuzumab is 45 mg; and

(ii) a single dose (C1D1) of polatuzumab vedotin, wherein the C1D1 of polatuzumab vedotin is 1.8 mg/kg;

(b) the second to sixth dosing cycles each comprises a single dose (C2D1-C6D1) of mosunetuzumab and a single dose (C2D1-C6D1) of polatuzumab vedotin, wherein each single dose C2D1-C6D1 of mosunetuzumab is 45 mg, and wherein each single dose C2D1-C6D1 of polatuzumab vedotin is 1.8 mg/kg; and

(c) the seventh and eighth dosing cycles each comprises a single dose C7D1 and C8D1, respectively, of mosunetuzumab and does not comprise administration of polatuzumab vedotin, wherein each single dose C7D1 and C8D1 is 45 mg, and

wherein the C1D1, C1D2, and C1D3 of mosunetuzumab are administered on or about Days 1, 8, and 15, respectively, of the first dosing cycle, each single dose of the C2D1-C8D1 of mosunetuzumab is administered on Day 1 of each respective dosing cycle, and each single dose of the C1D1-C6D1 of polatuzumab vedotin is administered on Day 1 of each respective dosing cycle.

8. The method of claim 7 , wherein:

(a) the C1D1 of polatuzumab vedotin is administered prior to administration of the C1D1 of mosunetuzumab, and wherein the C2D1 of polatuzumab vedotin is administered prior to administration of the C2D1 of mosunetuzumab; and/or

(b) each single dose C3D1-C6D1 of polatuzumab vedotin is administered prior to administration of each single dose C3D1-C6D1 of mosunetuzumab, respectively.

9. The method of claim 8 , wherein polatuzumab vedotin is administered at least about 60 minutes prior to administration of mosunetuzumab.

10. The method of claim 1 , wherein the method further comprises administering to the subject one or more additional therapeutic agents.

11. The method of claim 10 , wherein the one or more additional therapeutic agents is a corticosteroid or an IL-6R antagonist.

12. The method of claim 11 , wherein:

(a) the IL-6R antagonist is tocilizumab, and wherein tocilizumab is administered:

(i) to the subject as a single dose of 8 mg/kg or 12 mg/kg, and wherein the single dose does not exceed 800 mg; and/or

(ii) intravenously;

(b) the corticosteroid is dexamethasone, and wherein dexamethasone is administered:

(i) as a single dose of 10 mg every 6 hours;

(ii) as a single dose of 20 mg prior to administration of any dose of mosunetuzumab; and/or

(iii) orally or intravenously;

(c) the corticosteroid is prednisone, and wherein prednisone is administered:

(i) at a dose of 10-30 mg/day; and/or

(ii) orally; or

(d) the corticosteroid is methylprednisolone, and wherein methylprednisolone is administered:

(i) at a dose of 1000 mg/day; and/or

(ii) intravenously.

13. The method of claim 10 , wherein the one or more additional therapeutic agents is:

(a) acetaminophen or paracetamol, wherein acetaminophen or paracetamol is administered:

(i) as a single dose of 500-1000 mg prior to administration of any dose of polatuzumab vedotin; and/or

(ii) orally; or

(b) diphenhydramine, wherein diphenhydramine is administered:

(i) as a single dose of 50-100 mg prior to administration of any dose of polatuzumab vedotin; and/or

(ii) orally.

14. The method of claim 1 , wherein the B cell proliferative disorder is a non-Hodgkin's lymphoma (NHL), a chronic lymphoid leukemia (CLL), or a central nervous system lymphoma (CNSL).

15. The method of claim 14 , wherein the NHL is:

(a) a diffuse-large B cell lymphoma (DLBCL), a follicular lymphoma (FL), a high-grade B cell lymphoma (HGBL), a mantle cell lymphoma (MCL), a high-grade B cell lymphoma, a primary mediastinal (thymic) large B cell lymphoma (PMLBCL), a diffuse B cell lymphoma, a small lymphocytic lymphoma, a marginal zone lymphoma (MZL), a Burkitt lymphoma, or a lymphoplasmacytic lymphoma;

(b) a relapsed and/or refractory (R/R) NHL; and/or

(c) an aggressive NHL, wherein the aggressive NHL is a DLBCL, a transformed FL, or a Grade 3b FL.

16. The method of claim 15 , wherein the NHL is:

(a) a DLBCL, and wherein the DLBCL is:

(i) an R/R DLBCL; and/or

(ii) a Richter's transformation;

(b) an FL, and wherein the FL is:

(i) an R/R FL; and/or

(ii) a transformed FL; or

(c) a HGBL, and wherein the HGBL is an R/R HGBL.

17. The method of claim 1 , wherein the subject:

(a) is ineligible for autologous stem cell transplant (ASCT);

(b) has relapsed after or is refractory to two or more prior lines of therapy; and/or

(c) is human.

18. A method of treating a population of subjects having a B cell proliferative disorder comprising subcutaneously administering to the subjects of the population mosunetuzumab and intravenously administering to the subjects of the population polatuzumab vedotin in a dosing regimen comprising eight 21-day dosing cycles, wherein:

(a) the first dosing cycle comprises:

(i) a first dose (C1D1) of mosunetuzumab, a second dose (C1D2) of mosunetuzumab, and a third dose (C1D3) of mosunetuzumab, wherein the C1D1 of mosunetuzumab is 5 mg, the C1D2 of mosunetuzumab is 45 mg, and the C1D3 of mosunetuzumab is 45 mg; and

(ii) a single dose (C1D1) of polatuzumab vedotin, wherein the C1D1 of polatuzumab vedotin is 1.8 mg/kg;

(b) the second to sixth dosing cycles each comprises a single dose (C2D1-C6D1) of mosunetuzumab and a single dose (C2D1-C6D1) of polatuzumab vedotin, wherein each single dose C2D1-C6D1 of mosunetuzumab is 45 mg, and wherein each single dose C2D1-C6D1 of polatuzumab vedotin is 1.8 mg/kg; and

(c) the seventh and eighth dosing cycles each comprises a single dose C7D1 and C8D1, respectively, of mosunetuzumab and does not comprise administration of polatuzumab vedotin, wherein each single dose C7D1 and C8D1 is 45 mg, and

wherein the C1D1, C1D2, and C1D3 of mosunetuzumab are administered on or about Days 1, 8, and 15, respectively, of the first dosing cycle, each single dose of the C2D1-C8D1 of mosunetuzumab is administered on Day 1 of each respective dosing cycle, and each single dose of the C1D1-C6D1 of polatuzumab vedotin is administered on Day 1 of each respective dosing cycle.

19. The method of claim 18 , wherein:

(a) the average duration of progression-free survival of the population of subjects is higher than a reference average duration of progression-free survival of a reference population of subjects;

(b) the complete response rate in the population of subjects is higher than a reference complete response rate in a reference population of subjects;

(c) the objective response rate in the population of subjects is higher than a reference objective response rate in a reference population of subjects;

(d) the average duration of response of the population of subjects is higher than a reference average duration of response of a reference population of subjects; and/or

(e) the average duration of complete response of the population of subjects is higher than a reference average duration of complete response of a reference population of subjects.

20. The method of claim 19 , wherein the reference population of subjects is administered a combination therapy comprising rituximab, gemcitabine, and oxaliplatin.

21. The method of claim 20 , wherein:

(a) the combination therapy is administered to the reference population of subjects in a dosing cycle comprising eight dosing cycles and/or about every two weeks (Q2W); and/or

(b) rituximab is administered intravenously at a dose of 375 mg/m 2 Q2W, gemcitabine is administered intravenously at a dose of 1000 mg/m 2 Q2W, and oxaliplatin is administered intravenously at a dose of 100 mg/m 2 Q2W.

22. The method of claim 21 , wherein each dosing cycle is a 14-day dosing cycle.

23. The method of claim 19 , wherein each subject in the reference population of subjects has a B cell proliferative disorder.

24. The method of claim 18 , wherein the B cell proliferative disorder is a non-Hodgkin's lymphoma (NHL), a chronic lymphoid leukemia (CLL), or a central nervous system lymphoma (CNSL).

25. The method of claim 24 , wherein the NHL is:

(a) a diffuse-large B cell lymphoma (DLBCL), a follicular lymphoma (FL), a high-grade B cell lymphoma (HGBL), a mantle cell lymphoma (MCL), a high-grade B cell lymphoma, a primary mediastinal (thymic) large B cell lymphoma (PMLBCL), a diffuse B cell lymphoma, a small lymphocytic lymphoma, a marginal zone lymphoma (MZL), a Burkitt lymphoma, or a lymphoplasmacytic lymphoma;

(b) a relapsed and/or refractory (R/R) NHL; and/or

(c) an aggressive NHL, wherein the aggressive NHL is a DLBCL, a transformed FL, or a Grade 3b FL.

26. The method of claim 25 , wherein the NHL is:

(a) a DLBCL, and wherein the DLBCL is:

(i) an R/R DLBCL; and/or

(ii) a Richter's transformation;

(b) an FL, and wherein the FL is:

(i) an R/R FL; and/or

(ii) a transformed FL; or

(c) a HGBL, and wherein the HGBL is an R/R HGBL.

27. The method of claim 18 wherein each subject in the population of subjects:

(a) is ineligible for autologous stem cell transplant (ASCT);

(b) has relapsed after or is refractory to two or more prior lines of therapy; and/or

(c) is human.

28. The method of claim 19 , wherein each subject in the reference population of subjects:

(a) is ineligible for autologous stem cell transplant (ASCT);

(b) has relapsed after or is refractory to two or more prior lines of therapy; and/or

(c) is human.

29. The method of claim 23 , wherein the B cell proliferative disorder is a non-Hodgkin's lymphoma (NHL), a chronic lymphoid leukemia (CLL), or a central nervous system lymphoma (CNSL).

30. The method of claim 29 , wherein the NHL is:

(a) a diffuse-large B cell lymphoma (DLBCL), a follicular lymphoma (FL), a high-grade B cell lymphoma (HGBL), a mantle cell lymphoma (MCL), a high-grade B cell lymphoma, a primary mediastinal (thymic) large B cell lymphoma (PMLBCL), a diffuse B cell lymphoma, a small lymphocytic lymphoma, a marginal zone lymphoma (MZL), a Burkitt lymphoma, or a lymphoplasmacytic lymphoma;

(b) a relapsed and/or refractory (R/R) NHL; and/or

(c) an aggressive NHL, wherein the aggressive NHL is a DLBCL, a transformed FL, or a Grade 3b FL.

31. The method of claim 30 , wherein the NHL is:

(a) a DLBCL, and wherein the DLBCL is:

(i) an R/R DLBCL; and/or

(ii) a Richter's transformation;

(b) an FL, and wherein the FL is:

(i) an R/R FL; and/or

(ii) a transformed FL; or

(c) a HGBL, and wherein the HGBL is an R/R HGBL.

32. A method of treating a subject having a B cell proliferative disorder comprising subcutaneously administering to the subject mosunetuzumab and intravenously administering to the subject polatuzumab vedotin in a dosing regimen comprising at least a first 21-day dosing cycle and a second 21-day dosing cycle, wherein:

(a) the first dosing cycle comprises a first dose (C1D1) of mosunetuzumab, a second dose (C1D2) of the mosunetuzumab, a third dose (C1D3) of mosunetuzumab, and a first dose (C1D1) of polatuzumab vedotin, wherein the C1D1 of mosunetuzumab is 5 mg, the C1D2 of mosunetuzumab is 45 mg, and the C1D3 of mosunetuzumab is 45 mg, and wherein the C1D1 of polatuzumab vedotin is 1.8 mg/kg; and

(b) the second dosing cycle comprises a single dose (C2D1) of mosunetuzumab and a single dose (C2D1) of polatuzumab vedotin, wherein the C2D1 of mosunetuzumab is 45 mg, and wherein the C2D1 of polatuzumab vedotin is 1.8 mg/kg, and

wherein the C1D1, C1D2, and C1D3 of mosunetuzumab are administered on or about Days 1, 8, and 15, respectively, of the first dosing cycle, the C1D1 of polatuzumab vedotin is administered on Day 1 of the first dosing cycle, the C2D1 of polatuzumab vedotin is administered on Day 1 of the second dosing cycle, and the C1D1 of polatuzumab vedotin is administered prior to administration of the C1D1 of mosunetuzumab.

33. The method of claim 32 , wherein:

(a) the C1D1 of polatuzumab vedotin is administered prior to administration of the C1D1 of mosunetuzumab, and wherein the C2D1 of polatuzumab vedotin is administered prior to administration of the C2D1 of mosunetuzumab; and/or

(b) the method further comprises one or more additional dosing cycles.

34. The method of claim 33 , wherein the method comprises six additional dosing cycles.

35. The method of claim 33 , wherein:

(a) each additional dosing cycle is a 21-day dosing cycle; and/or

(b) the one or more of the additional dosing cycles each comprise an additional single dose of mosunetuzumab and an additional single dose of polatuzumab vedotin, or the one or more of the additional dosing cycles each comprise an additional single dose of mosunetuzumab and do not comprise administration of polatuzumab vedotin.

36. The method of claim 35 , wherein:

(a) the additional single dose of polatuzumab vedotin is 1.8 mg/kg;

(b) each additional single dose of polatuzumab vedotin is administered to the subject on Day 1 of each additional dosing cycle comprising an additional dose of polatuzumab vedotin;

(c) the additional single dose of mosunetuzumab is 45 mg; and/or

(d) each additional single dose of mosunetuzumab is administered to the subject on Day 1 of each additional dosing cycle comprising an additional dose of mosunetuzumab.

37. The method of claim 35 , wherein the dosing regimen comprises six additional dosing cycles, wherein each of the six additional dosing cycles comprises a single dose of mosunetuzumab, and wherein no more than four of the six additional dosing cycles comprise administration of polatuzumab vedotin.

38. The method of claim 32 , wherein the method further comprises administering to the subject one or more additional therapeutic agents.

39. The method of claim 38 , wherein the one or more additional therapeutic agents is a corticosteroid or an IL-6R antagonist.

40. The method of claim 39 , wherein:

(a) the IL-6R antagonist is tocilizumab, and wherein tocilizumab is administered:

(i) to the subject as a single dose of 8 mg/kg or 12 mg/kg, and wherein the single dose does not exceed 800 mg; and/or

(ii) intravenously;

(b) the corticosteroid is dexamethasone, and wherein dexamethasone is administered:

(i) as a single dose of 10 mg every 6 hours;

(ii) as a single dose of 20 mg prior to administration of any dose of mosunetuzumab; and/or

(iii) orally or intravenously;

(c) the corticosteroid is prednisone, and wherein prednisone is administered:

(i) at a dose of 10-30 mg/day; and/or

(ii) orally; or

(d) the corticosteroid is methylprednisolone, and wherein methylprednisolone is administered:

(i) at a dose of 1000 mg/day; and/or

(ii) intravenously.

41. The method of claim 38 , wherein the one or more additional therapeutic agents is:

(a) acetaminophen or paracetamol, wherein acetaminophen or paracetamol is administered:

(i) as a single dose of 500-1000 mg prior to administration of any dose of polatuzumab vedotin; and/or

(ii) orally; or

(b) diphenhydramine, wherein diphenhydramine is administered:

(i) as a single dose of 50-100 mg prior to administration of any dose of polatuzumab vedotin; and/or

(ii) orally.

42. The method of claim 32 , wherein the B cell proliferative disorder is a non-Hodgkin's lymphoma (NHL), a chronic lymphoid leukemia (CLL), or a central nervous system lymphoma (CNSL).

43. The method of claim 42 , wherein the NHL is:

(a) a diffuse-large B cell lymphoma (DLBCL), a follicular lymphoma (FL), a high-grade B cell lymphoma (HGBL), a mantle cell lymphoma (MCL), a high-grade B cell lymphoma, a primary mediastinal (thymic) large B cell lymphoma (PMLBCL), a diffuse B cell lymphoma, a small lymphocytic lymphoma, a marginal zone lymphoma (MZL), a Burkitt lymphoma, or a lymphoplasmacytic lymphoma;

(b) a relapsed and/or refractory (R/R) NHL; and/or

(c) an aggressive NHL, wherein the aggressive NHL is a DLBCL, a transformed FL, or a Grade 3b FL.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 16, 2022
From: O'HEAR, CAROL ELAINE; OKI, YASUHIRO; TO, IRIS TRANTHUYNGAN
To: GENENTECH, INC.
Reel/Frame 060227/0421 →
Continuity (3)
Provisional Application 63292887 · Dec 22, 2021
Provisional Application 63188695 · May 14, 2021
Related Publication 20220411528A1 · Dec 29, 2022
References Cited (400)
US 5500362A · Robinson et al. · 1996 [cited by applicant]
US 5624821A · Winter et al. · 1997 [cited by applicant]
US 5648260A · Winter et al. · 1997 [cited by applicant]
US 5677171A · Hudziak 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 7435797B2 · Lowman et al. · 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 7951546B2 · Frantz et al. · 2011 [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 9714294B2 · De Goeij 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 · 2022 [cited by examiner]
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 20140170148A1 · De Goeij 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 20150079093A1 · Stuhler · 2015 [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 20160082120A1 · Polson · 2016 [cited by examiner]
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 et al. · 2018 [cited by applicant]
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 20200339686A1 · Sato et al. · 2020 [cited by applicant]
US 20220153842A1 · Li et al. · 2022 [cited by applicant]
CN 102281902A · 2011 [cited by applicant]
CN 102369218A · 2012 [cited by applicant]
CN 102471380A · 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 2789630A1 · 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 2010524435A · 2010 [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 WO03087131A2 · 2003 [cited by applicant]
WO WO2004056312A2 · 2004 [cited by applicant]
WO WO2004106380A2 · 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 WO2010120561A1 · 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 WO2014012085A2 · 2014 [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 WO2014081955A1 · 2014 [cited by applicant]
WO WO2014082179A1 · 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 WO2015013671A1 · 2015 [cited by applicant]
WO WO2014191113A8 · 2015 [cited by applicant]
WO WO2015018527A1 · 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 WO2016135239A1 · 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]
Wolska-Washer et al (Drug Safety, 2019, 42: 295-314). [cited by examiner]
Trněný et al.(Haematologica, 2018, 103(8): 1351-1358). [cited by examiner]
WHO Drug Information (vol. 31, No. 2, 2017). [cited by examiner]
“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/purif… [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]
Brekke et al., “Human IgG isotype-specific amino acid residues affecting complement-mediated cell lysis and phagocytosis,” Eur J Immunol. 24(10):2542-7 (1994). [cited by applicant]
Brinkmann et al., “The making of bispecific antibodies,” mAbs. 9(2):182-212 (Nov. 2017). [cited by applicant]
Brown et al., “Tolerance of single, but not multiple, amino acid replacements in antibody VH CDR2: a means of minimizing B cell wastage from somatic hypermutation?” J Immunol. 156(9):3285-91 (1996). [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]
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]
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 circulating and lymphoid B cells in monkeys: a potential thera… [cited by applicant]
Clark et al., “Affinity enhancement of an in vivo matured therapeutic antibody using structure-based computational design,” Protein Sci. 15(5):949-60 (2006). [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,” 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 (Aug. 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]
Genentech, “A Phase I Study of BTRC4017A in Participants With Locally Advanced or Metastatic HER2-Expressing Cancers,” ClinicalTrials.gov, <https://clinicaltrials.gov/ct2/show/NCT03448042?term=BTRC4017 A&draw=2&rank=1>,… [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]
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 (Jan. 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]
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]
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, “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-cell engagers for cancer immunotherapy,” Immunol Cell Biol. 93(3):290-6 (2015). [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 (Sep. 2021). [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]
Kegg Drug Database Accession No. D03257, “Drug: Trastuzumab,” <https://www.genome.jp/dbget-bin/www_bget?dr:D03257>, retrieved on Jan. 8, 2019 (2 pages). [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]
Kong et al., “Characterization and function of human Ly-6/uPAR molecules,” BMB Rep. 45(11):595-603 (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 (2019) (1 page). [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-TGFβ1 antibody,” MAbs. 10(3):444-452 (2018) (10 pages). [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 (May 2016) (Abstract only) (3 pages). [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]
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]
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-delta and T3-epsilon) 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]
Philips et al., “Therapeutic uses of anti-PD-1 and anti-PD-L1 antibodies,” Int Immunol 27(1):39-46 (2014). [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):183-190 (… [cited by applicant]
Ridgway et al., “‘Knobs-into-holes’ engineering of antibody CH3 domains for heavy chain heterodimerization,” Protein Eng. 9(7):617-21 (1996). [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]
Schuster et al., “Mosunetuzumab Induces Complete Remissions in Poor Prognosis Non-Hodgkin Lymphoma Patients, Including Those Who Are Resistant to or Relapsing After Chimeric Antigen Receptor T-Cell (CAR-T) Therapies, an… [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 [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 [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, retrieved from <https://www.sciencedirect.com/science/article/pii/S016158901500005X?… [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]
Yang et al., “Improving Trastuzumab's Stability Profile by Removing the Two Degradation Hotspots,” J Pharm Sci. 104(6):1960-70 (2015). [cited by applicant]
“Small data transmission (S2-113410),” IPWireless Inc., SA WG2 Meeting #86, Jul. 11-15, Naantali, Finland, agenda item 9.4 (2011) (6 pages). [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]
Extended European Search Report for European Patent Application No. 20170466.5, dated Sep. 24, 2020 (14 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]
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]
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. 1, 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]
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]
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]
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]