IP Library › Granted Patent US 12,325,742
Granted Patent B2
US 12,325,742 · App. 17/259,677 · Granted Jun 10, 2025

Anti-mesothelin antibodies

Inventors: Jose Munoz-Olaya (Cambridge, GB); Remi Fertin (Cambridge, GB); Francisca Wollerton (Cambridge, GB); Mihriban Tuna (Cambridge, GB); Neil Brewis (Cambridge, GB)
Assignee: INVOX PHARMA LIMITED
C07K16/18A61P35/00C07K16/2878G01N33/57496A61K2039/505C07K2317/31C07K2317/33C07K2317/524C07K2317/526C07K2317/55C07K2317/565C07K2317/732C07K2317/76C07K2317/92
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 12,325,742
App. No.
17/259,677
Granted
Jun 10, 2025
Kind
B2
Abstract

The present application relates to antibody molecules that bind mesothelin (MSLN). The antibody molecules find application in the treatment and diagnosis of diseases and disorders, such as cancer.

Claims (72)

1. An antibody molecule that binds mesothelin (MSLN), wherein the antigen-binding site of the antibody molecule comprises the VH domain CDR1, CDR2 and CDR3 and the VL domain CDR1, CDR2 and CDR3 of antibody:

(i) FS28-256-271 set forth in SEQ ID NO: 98, 73, 99, 20, 21, and 44, respectively;

(ii) FS28-024-052 set forth in SEQ ID NO: 10, 11, 41, 20, 21 and 22, respectively;

(iii) FS28-256-021 set forth in SEQ ID NO: 98, 73, 99, 20, 21 and 34, respectively;

(iv) FS28-256-012 set forth in SEQ ID NO: 98, 73, 99, 20, 21 and 25, respectively;

(v) FS28-256-023 set forth in SEQ ID NO: 101, 73, 103, 20, 21 and 34, respectively;

(vi) FS28-256-024 set forth in SEQ ID NO: 98, 73, 99, 20, 21 and 43, respectively;

(vii) FS28-256-026 set forth in SEQ ID NO: 101, 73, 103, 20, 21 and 43, respectively;

(viii) FS28-256-027 set forth in SEQ ID NO: 98, 73, 99, 20, 21 and 44, respectively;

(ix) FS28-256-001 set forth in SEQ ID NO: 85, 73, 75, 20, 21 and 34, respectively;

(x) FS28-256-005 set forth in SEQ ID NO: 85, 73, 75, 20, 21 and 43, respectively;

(xi) FS28-256-014 set forth in SEQ ID NO: 111, 73, 113, 20, 21 and 25, respectively;

(xii) FS28-256-018 set forth in SEQ ID NO: 101, 73, 103, 20, 21 and 25, respectively;

(xiii) FS28-256 set forth in SEQ ID NO: 71, 73, 75, 20, 21 and 25, respectively;

(xiv) FS28-024-051 set forth in SEQ ID NO: 10, 11, 32, 20, 21 and 22, respectively;

(xv) FS28-024-053 set forth in SEQ ID NO: 10, 11, 51, 20, 21 and 22, respectively; or

(xvi) FS28-024 set forth in SEQ ID NO: 10, 11, 12, 20, 21 and 22, respectively; and

wherein the CDR sequences are defined according to the ImMunoGeneTics (IMGT) numbering scheme; and/or

wherein the antigen-binding site of the antibody molecule comprises the VH domain CDR1, CDR2 and CDR3 and the VL domain CDR1, CDR2 and CDR3 of antibody:

(i) FS28-256-271 set forth in SEQ ID NO: 97, 182, 100, 23, 24, and 44, respectively;

(ii) FS28-024-052 set forth in SEQ ID NO: 13, 14, 42, 23, 24 and 22, respectively;

(iii) FS28-256-021 set forth in SEQ ID NO: 97, 74, 100, 23, 24 and 34, respectively;

(iv) FS28-256-012 set forth in SEQ ID NO: 97, 74, 100, 23, 24 and 25, respectively;

(v) FS28-256-023 set forth in SEQ ID NO: 102, 74, 104, 23, 24 and 34, respectively;

(vi) FS28-256-024 set forth in SEQ ID NO: 97, 74, 100, 23, 24 and 43, respectively;

(vii) FS28-256-026 set forth in SEQ ID NO: 102, 74, 104, 23, 24 and 43, respectively;

(viii) FS28-256-027 set forth in SEQ ID NO: 97, 74, 100, 23, 24 and 44, respectively;

(ix) FS28-256-001 set forth in SEQ ID NO: 86, 74, 76, 23, 24 and 34, respectively;

(x) FS28-256-005 set forth in SEQ ID NO: 86, 74, 76, 23, 24 and 43, respectively;

(xi) FS28-256-014 set forth in SEQ ID NO: 112, 74, 114, 23, 24 and 25, respectively;

(xii) FS28-256-018 set forth in SEQ ID NO: 102, 74, 104, 23, 24 and 25, respectively;

(xiii) FS28-256 set forth in SEQ ID NO: 72, 74, 76, 23, 24 and 25, respectively;

(xiv) FS28-024-051 set forth in SEQ ID NO: 13, 14, 33, 23, 24 and 22, respectively;

(xiv) FS28-024-053 set forth in SEQ ID NO: 13, 14, 52, 23, 24 and 22, respectively; or

(xvi) FS28-024 set forth in SEQ ID NO: 13, 14, 15, 23, 24 and 22, respectively; and

wherein the CDR sequences are defined according to the Kabat numbering scheme; and

wherein the antibody molecule does not comprise a CD137 antigen-binding site located in a CH3 domain of the antibody molecule, said CD137 antigen-binding site comprising a first sequence as set forth in SEQ ID NO: 198 located in the AB structural loop of the CH3 domain and a second sequence as set forth in SEQ ID NO: 199 located in the EF structural loop of the CH3 domain.

2. The antibody molecule according to claim 1 , comprising the VH domain and VL domain of antibody:

(i) FS28-256-271 set forth in SEQ ID NO: 180 and 56, respectively;

(ii) FS28-024-052 set forth in SEQ ID NO: 39 and 18, respectively;

(iii) FS28-256-021 set forth in SEQ ID NO: 109 and 93, respectively;

(iv) FS28-256-012 set forth in SEQ ID NO: 109 and 79, respectively;

(v) FS28-256-023 set forth in SEQ ID NO: 121 and 93, respectively;

(vi) FS28-256-024 set forth in SEQ ID NO: 109 and 53, respectively;

(vii) FS28-256-026 set forth in SEQ ID NO: 121 and 53, respectively;

(viii) FS28-256-027 set forth in SEQ ID NO: 109 and 56, respectively;

(ix) FS28-256-001 set forth in SEQ ID NO: 63 and 93, respectively;

(x) FS28-256-005 set forth in SEQ ID NO: 63 and 53, respectively;

(xi) FS28-256-014 set forth in SEQ ID NO: 115 and 79, respectively;

(xii) FS28-256-018 set forth in SEQ ID NO: 121 and 79, respectively;

(xiii) FS28-256 set forth in SEQ ID NO: 69 and 79, respectively;

(xiv) FS28-024-051 set forth in SEQ ID NO: 30 and 18, respectively;

(xv) FS28-024-053 set forth in SEQ ID NO: 49 and 18, respectively; or

(xvi) FS28-024 set forth in SEQ ID NO: 8 and 18, respectively.

3. The antibody molecule according to claim 1 , wherein the antigen-binding site of the antibody molecule comprises the VH domain CDR1, CDR2 and CDR3 and the VL domain CDR1, CDR2 and CDR3 of antibody FS28-256-271 set forth in SEQ ID NO: 98, 73, 99, 20, 21, and 44, respectively, wherein the CDR sequences are defined according to the IMGT numbering scheme; the VH domain CDR1, CDR2 and CDR3 and the VL domain CDR1, CDR2 and CDR3 of antibody FS28-256-271 set forth in SEQ ID NO: 97, 182, 100, 23, 24, and 44, respectively, wherein the CDR sequences are defined according to the Kabat numbering scheme; and/or the VH and VL domain of antibody FS28-256-271 set forth in SEQ ID NO: 180 and 56, respectively.

4. The antibody molecule according to claim 1 , wherein the antigen-binding site of the antibody molecule comprises the VH domain CDR1, CDR2 and CDR3 and the VL domain CDR1, CDR2 and CDR3 of antibody FS28-024-052 set forth in SEQ ID NO: 10, 11, 41, 20, 21 and 22, respectively, wherein the CDR sequences are defined according to the IMGT numbering scheme; the VH domain CDR1, CDR2 and CDR3 and the VL domain CDR1, CDR2 and CDR3 of antibody FS28-024-052 set forth in SEQ ID NO: 13, 14, 42, 23, 24 and 22, respectively, wherein the CDR sequences are defined according to the Kabat numbering scheme; and/or the VH and VL domain of antibody FS28-024-052 set forth in SEQ ID NO: 39 and 18, respectively.

5. The antibody molecule according to claim 1 , wherein antibody molecule is a multispecific antibody molecule and comprises a second antigen-binding site that binds a second antigen.

6. The antibody molecule according to claim 5 , wherein the second antigen-binding site is located in a constant domain of the antibody molecule.

7. The antibody molecule according to claim 6 , wherein the constant domain is a CH3 domain.

8. The antibody molecule according to claim 5 , wherein the second antigen-binding site binds an immune cell antigen.

9. The antibody molecule according to claim 8 , wherein the immune cell antigen is a member of the tumour necrosis factor receptor superfamily (TNFRSF).

10. The antibody molecule according to claim 9 , wherein the member of the TNFRSF is CD137.

11. The antibody molecule according to claim 6 , wherein the second antigen-binding site comprises a first sequence, a second sequence, and/or a third sequence, wherein the first sequence, second sequence and third sequence are located in the AB structural loop, the CD structural loop and the EF structural loop of the constant domain, respectively.

12. The antibody molecule according to claim 8 , wherein the antibody molecule is capable of activating an immune cell in the presence of MSLN.

13. The antibody molecule according to claim 12 , wherein the immune cell is a T cell, B cell, natural killer (NK) cell, natural killer T (NKT) cell, or dendritic cell (DC).

14. The antibody molecule according to claim 1 , wherein the antibody molecule has been modified to reduce or abrogate binding of the CH2 domain of the antibody molecule to one or more Fcγ receptors.

15. The antibody molecule according to claim 14 , wherein the antibody molecule does not bind to one or more Fcγ receptors.

16. A nucleic acid molecule or molecules encoding the antibody molecule according claim 1 .

17. A recombinant host cell comprising the nucleic acid molecules(s) according to claim 16 .

18. A pharmaceutical composition comprising the antibody molecule according to claim 1 and a pharmaceutically acceptable excipient.

19. A method of detecting or diagnosing a cancer in an individual, the method comprising the use of the antibody molecule according to claim 1 .

20. A method of treating cancer in an individual comprising administering to the individual a therapeutically effective amount of the antibody molecule according to claim 1 .

Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 24, 2024
From: F-STAR THERAPEUTICS LIMITED
To: INVOX PHARMA LIMITED
Reel/Frame 068673/0457 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 13, 2021
From: F-STAR BETA LIMITED
To: F-STAR THERAPEUTICS LIMITED
Reel/Frame 058373/0445 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 24, 2021
From: MUNOZ-OLAYA, JOSE; FERTIN, REMI; WOLLERTON, FRANCISCA; TUNA, MIHRIBAN; BREWIS, NEIL
To: F-STAR BETA LIMITED
Reel/Frame 055695/0840 →
Priority Claims (1)
GB 1811415 · Jul 12, 2018 · national
Continuity (1)
Related Publication 20220267421A1 · Aug 25, 2022
References Cited (366)
US 3909459A · Friese et al. · 1975 [cited by applicant]
US 3967230A · Kamigaito et al. · 1976 [cited by applicant]
US 4004183A · Oki et al. · 1977 [cited by applicant]
US 5595756A · Bally et al. · 1997 [cited by applicant]
US 6380664B1 · Pollner · 2002 [cited by applicant]
US 7288638B2 · Jure-Kunkel et al. · 2007 [cited by applicant]
US 7592426B2 · Ebel et al. · 2009 [cited by applicant]
US 8217149B2 · Irving et al. · 2012 [cited by applicant]
US 8383796B2 · Korman et al. · 2013 [cited by applicant]
US 8911732B2 · Dennis et al. · 2014 [cited by applicant]
US 9567399B1 · Campbell et al. · 2017 [cited by applicant]
US 9617338B1 · Campbell et al. · 2017 [cited by applicant]
US 10090646B2 · Takaoka et al. · 2018 [cited by applicant]
US 10205305B2 · Uegaki et al. · 2019 [cited by applicant]
US 10233258B2 · Akamatsu et al. · 2019 [cited by applicant]
US 10604576B2 · Campbell et al. · 2020 [cited by applicant]
US 11214618B2 · Tuna et al. · 2022 [cited by applicant]
US 11214620B2 · Campbell et al. · 2022 [cited by applicant]
US 11548948B2 · Tuna et al. · 2023 [cited by applicant]
US 11629193B2 · Tuna et al. · 2023 [cited by applicant]
US 12103976B2 · Lakins et al. · 2024 [cited by applicant]
US 20030030355A1 · Honda · 2003 [cited by applicant]
US 20070071675A1 · Wu et al. · 2007 [cited by applicant]
US 20090055944A1 · Korman et al. · 2009 [cited by applicant]
US 20120237498A1 · Ahrens et al. · 2012 [cited by applicant]
US 20120276104A1 · Woisetschlager · 2012 [cited by applicant]
US 20130034559A1 · Queva et al. · 2013 [cited by applicant]
US 20140004121A1 · Fanslow, III et al. · 2014 [cited by applicant]
US 20140341917A1 · Nastri et al. · 2014 [cited by applicant]
US 20150214697A1 · Yoshida et al. · 2015 [cited by applicant]
US 20150259420A1 · Triebel et al. · 2015 [cited by applicant]
US 20150307620A1 · Vella et al. · 2015 [cited by applicant]
US 20160043531A1 · Firstenberg et al. · 2016 [cited by applicant]
US 20160137740A1 · Hammond et al. · 2016 [cited by applicant]
US 20160244528A1 · Gray et al. · 2016 [cited by applicant]
US 20170198050A1 · Eckelman et al. · 2017 [cited by applicant]
US 20170355756A1 · Julien et al. · 2017 [cited by applicant]
US 20170362321A1 · Campbell et al. · 2017 [cited by applicant]
US 20180118841A1 · Ellmark et al. · 2018 [cited by applicant]
US 20180175592A1 · Uegaki et al. · 2018 [cited by applicant]
US 20180194862A1 · Akamatsu et al. · 2018 [cited by applicant]
US 20180339031A1 · Masternak et al. · 2018 [cited by applicant]
US 20190106494A1 · Wang et al. · 2019 [cited by applicant]
US 20190202920A1 · Tuna et al. · 2019 [cited by applicant]
US 20190256602A1 · Campbell et al. · 2019 [cited by applicant]
US 20190330344A1 · Tuna et al. · 2019 [cited by applicant]
US 20190330351A1 · Campbell et al. · 2019 [cited by applicant]
US 20190338032A1 · Campbell et al. · 2019 [cited by applicant]
US 20190338049A1 · Tuna et al. · 2019 [cited by applicant]
US 20200407446A1 · McCourt et al. · 2020 [cited by applicant]
US 20210139590A1 · Tuna et al. · 2021 [cited by applicant]
US 20210237498A1 · Yoda et al. · 2021 [cited by applicant]
US 20210238299A1 · Pechouckova et al. · 2021 [cited by applicant]
US 20210277134A1 · Lakins et al. · 2021 [cited by applicant]
US 20210301022A1 · Wollerton et al. · 2021 [cited by applicant]
US 20210309753A1 · Tuna et al. · 2021 [cited by applicant]
US 20210355228A1 · Lakins et al. · 2021 [cited by applicant]
US 20220048996A1 · Tuna et al. · 2022 [cited by applicant]
US 20220049007A1 · Lakins et al. · 2022 [cited by applicant]
US 20220185890A1 · Tuna et al. · 2022 [cited by applicant]
US 20220185894A1 · Campbell et al. · 2022 [cited by applicant]
US 20220275092A1 · Morrow et al. · 2022 [cited by applicant]
US 20230357413A1 · Tuna et al. · 2023 [cited by applicant]
US 20230406935A1 · Tuna et al. · 2023 [cited by applicant]
CN 101802006A · 2010 [cited by applicant]
CN 104955845A · 2015 [cited by applicant]
CN 104968364A · 2015 [cited by applicant]
CN 107523546A · 2017 [cited by applicant]
CN 109563171A · 2019 [cited by applicant]
EP 1025230B1 · 2006 [cited by applicant]
EP 1180123B1 · 2008 [cited by applicant]
EP 2407487A1 · 2012 [cited by applicant]
EP 2546268A1 · 2013 [cited by applicant]
EP 2242771B1 · 2013 [cited by applicant]
EP 2905030A1 · 2015 [cited by applicant]
EP 2215121B1 · 2016 [cited by applicant]
EP 3354661A1 · 2018 [cited by applicant]
EP 3470426A1 · 2019 [cited by applicant]
JP S51046628A · 1976 [cited by applicant]
JP 2003022886A · 2003 [cited by applicant]
JP 22011521905A · 2011 [cited by applicant]
JP 2012500006A · 2012 [cited by applicant]
JP 2016513467A · 2016 [cited by applicant]
JP 2016533395A · 2016 [cited by applicant]
JP 2017010741A · 2017 [cited by applicant]
JP 2018508475A · 2018 [cited by applicant]
RU 2017112379A · 2018 [cited by applicant]
TW 201642897A · 2016 [cited by applicant]
WO WO2001077342A1 · 2001 [cited by applicant]
WO WO2005035584A1 · 2005 [cited by applicant]
WO WO2006072620A1 · 2006 [cited by applicant]
WO WO2006088447A1 · 2006 [cited by applicant]
WO WO2006099141A1 · 2006 [cited by applicant]
WO WO2008003103A2 · 2008 [cited by applicant]
WO WO2008068048A2 · 2008 [cited by applicant]
WO WO2009000006A1 · 2008 [cited by applicant]
WO WO2009068204A1 · 2009 [cited by applicant]
WO WO2009126944A1 · 2009 [cited by applicant]
WO WO2009132876A1 · 2009 [cited by applicant]
WO WO2010019570A2 · 2010 [cited by applicant]
WO WO2010057047A1 · 2010 [cited by applicant]
WO WO2010111282A1 · 2010 [cited by applicant]
WO WO2010124797A1 · 2010 [cited by applicant]
WO WO2012130831A1 · 2012 [cited by applicant]
WO WO2013181634A2 · 2013 [cited by applicant]
WO WO2014004549A2 · 2014 [cited by applicant]
WO WO2014008218A1 · 2014 [cited by applicant]
WO WO2014052064A1 · 2014 [cited by applicant]
WO WO2014089113A1 · 2014 [cited by applicant]
WO WO2014140180A1 · 2014 [cited by applicant]
WO WO2014151910A1 · 2014 [cited by applicant]
WO WO2015048312A1 · 2015 [cited by applicant]
WO WO2015049537A1 · 2015 [cited by applicant]
WO WO2015119923A1 · 2015 [cited by applicant]
WO WO2015138920A1 · 2015 [cited by applicant]
WO WO2015198312A1 · 2015 [cited by applicant]
WO WO2015200119A1 · 2015 [cited by applicant]
WO WO2016028672A1 · 2016 [cited by applicant]
WO WO2016040880A1 · 2016 [cited by applicant]
WO WO2016110584A1 · 2016 [cited by applicant]
WO WO2016111645A1 · 2016 [cited by applicant]
WO WO2016162505A1 · 2016 [cited by applicant]
WO WO2016177802A1 · 2016 [cited by applicant]
WO WO2016185016A1 · 2016 [cited by applicant]
WO WO2016200782A1 · 2016 [cited by applicant]
WO WO2017009456A1 · 2017 [cited by applicant]
WO WO2017015560A2 · 2017 [cited by applicant]
WO WO2017019846A8 · 2017 [cited by applicant]
WO WO2017025498A1 · 2017 [cited by applicant]
WO WO2017049452A1 · 2017 [cited by applicant]
WO WO2017052241A1 · 2017 [cited by applicant]
WO WO2017055398A2 · 2017 [cited by applicant]
WO WO2017062888A1 · 2017 [cited by applicant]
WO WO2017077085A2 · 2017 [cited by applicant]
WO WO2017087589A2 · 2017 [cited by applicant]
WO WO2017087901A2 · 2017 [cited by applicant]
WO WO2017123650A2 · 2017 [cited by applicant]
WO WO2017182672A1 · 2017 [cited by applicant]
WO WO2017193032A2 · 2017 [cited by applicant]
WO WO2017205738A1 · 2017 [cited by applicant]
WO WO2017220555A1 · 2017 [cited by applicant]
WO WO2017220569A1 · 2017 [cited by applicant]
WO WO2017220990A9 · 2017 [cited by applicant]
WO WO2018017673A1 · 2018 [cited by applicant]
WO WO2018056821A1 · 2018 [cited by applicant]
WO WO2018060480A1 · 2018 [cited by applicant]
WO WO2018091740A2 · 2018 [cited by applicant]
WO WO2018115859A1 · 2018 [cited by applicant]
WO WO2018127610A1 · 2018 [cited by applicant]
WO WO2018222711A2 · 2018 [cited by applicant]
WO WO2019025545A1 · 2019 [cited by applicant]
Lamberts et. al. (Clin. Cancer Res. 22(7) 1642-1652. (2016)) (Year: 2016). [cited by examiner]
Brinkmann et. al. MABS. 9(2):182-212. (2017) (Year: 2017). [cited by examiner]
U.S. Appl. No. 17/534,315, filed Nov. 23, 2021, Tuna et al. [cited by applicant]
U.S. Appl. No. 17/533,230, filed Nov. 23, 2021, Campbell et al. [cited by applicant]
U.S. Appl. No. 18/166,202, filed Feb. 8, 2023, Tuna et al. [cited by applicant]
U.S. Appl. No. 18/063,521, filed Dec. 8, 2022, Tuna et al. [cited by applicant]
U.S. Appl. No. 17/610,873, filed Nov. 12, 2021, Morrow et al. [cited by applicant]
[No Author Listed] Abstract for CHI Immuno-Oncology Summit Europe. Mar. 18-22, 2019. 1 page. PDR303. [cited by applicant]
[No Author Listed] First-in-Class bispecific antibodies for cancer immunotherapy. Presentation at Takeda. Dec. 13, 2016. 24 pages. PDR160. [cited by applicant]
[No Author Listed] F-Star Modular Bispecific Antibodies. Summary for ATLAS deck. Presented at JP Morgan. Jan. 2017. 1 page. PDR159. [cited by applicant]
[No Author Listed], Pipeline Overview: F-star is developing a pipeline of bispecific antibodies focused on oncology and immuno-oncology. F-Start website update. Sep. 2016. 2 pages. PDR126. [cited by applicant]
Ascierto et al., Initial efficacy of anti-lymphocyte activation gene-3 (anti-LAG-3:BMS-986016) in combination with nivolumab (nivo) in pts with melanoma (MEL) previously treated with anti-PD-1/PD-L1 therapy. J Clin Onco… [cited by applicant]
Bernett et al., Abstract P122: Multiple bispecific checkpoint combinations enhance T cell activity. J Immunother Cancer. 2016;4(Suppl 1):P122. 2 pages. [cited by applicant]
Bernett et al., Multiple bispecific checkpoint combinations enhance T cell activity. Xencor Poster Presentation. 2016. 1 page. [cited by applicant]
Bodhankar et al., PD-L1 Monoclonal Antibody Treats Ischemic Stroke by Controlling Central Nervous System Inflammation. Stroke. Oct. 2015;46(10):2926-34. doi: 10.1161/STROKEAHA.115.010592. Epub Aug. 25, 2015. [cited by applicant]
Brewis, Development of an anti-PD-L1 Fcab. Presentation. Human Antibodies and Hybrodomas Conference. Oct. 22, 2018. PDR 312. [cited by applicant]
Brewis, Identification of a PD-L1 binding Fcab: a potent inhibitor of immunosuppressive signals. Abstract. Huamn Antibodies and Hybridomas 2018. Jun. 11, 2018. 1 page. PDR282. [cited by applicant]
Brewis, The use of bispecific antibodies to modulate anti-tumour immune responses. Oral Presentation at ELRIG—Research and Innovation. Mar. 29, 2017. 33 pages. PDR177. [cited by applicant]
Brewis, The use of bispecific antibodies to modulate anti-tumour immune responses. Oral Presentation at PEPtalk. Jan. 12, 2017. 26 pages. PDR163. [cited by applicant]
Burova et al., Abstract 1484: Combined treatment with anti-LAG-3 and anti-PD-1 fully human monoclonal antibodies inhibits tumor growth in immunocompetent double-humanized LAG-3/PD-1 mice. Proceedings: AACR 107th Annual … [cited by applicant]
Burova et al., Abstract P195: A novel anti-human LAG-3 antibody in combination with anti-human PD-1 (REGN2810) shows enhanced anti-tumor activity in PD-1 x LAG-3 dual-humanized mice and favorable pharmacokinetic and saf… [cited by applicant]
Camisaschi et al., LAG-3 expression defines a subset of CD4(+)CD25(high)Foxp3(+) regulatory T cells that are expanded at tumor sites. J Immunol. Jun. 1, 2010;184(11):6545-51. doi: 10.4049/jimmunol.0903879. Epub Apr. 26,… [cited by applicant]
Cemerski et al., T cell activation and anti-tumor efficacy of anti-LAG-3 antibodies is independent of LAG-3-MHCII blocking capacity. Poster Presentation. 30th Annual Meeting and Associated Programs of the Society for Im… [cited by applicant]
Curran et al., PD-1 and CTLA-4 combination blockade expands infiltrating T cells and reduces regulatory T and myeloid cells within B16 melanoma tumors. Proc Natl Acad Sci U S A. Mar. 2, 2010;107(9):4275-80. doi: 10.1073… [cited by applicant]
Davies, Analytical challenges for next generation biologics. Oral Presentation at Waters Biopharma Mini-Seminar. May 24, 2017. 20 pages. PDR191. [cited by applicant]
Davies, Bispecific Antibodies: New Opportunities for Novel Therapies. Oral Presentation at Bioprocess UK 2016. Nov. 26, 2016. 14 pages. PDR 135. [cited by applicant]
Davies, Overcoming the Manufacturing Challenges for Bispecific mAbs. Oral Presentation at 5th Annual Cell Culture and Bioprocessing Congress. Nov. 6, 2016. 16 pages. PDR142. [cited by applicant]
Davies, Overcoming the Manufacturing Challenges for Bispecific mAbs. Oral Presentation at Biopronet 3rd Annual Scientific Symposium. Oct. 20, 2016. 16 pages. PDR136. [cited by applicant]
Daxini et al., Vasculitis associated with immune checkpoint inhibitors—a systematic review. Clin Rheumatol. Sep. 2018;37(9):2579-2584. doi: 10.1007/s10067-018-4177-0. Epub Jun. 19, 2018. [cited by applicant]
Demeure et al., T Lymphocytes infiltrating various tumour types express the MHC class II ligand lymphocyte activation gene-3 (LAG-3): role of LAG-3/MHC class II interactions in cell-cell contacts. Eur J Cancer. Sep. 200… [cited by applicant]
Deng et al., LAG-3 confers poor prognosis and its blockade reshapes antitumor response in head and neck squamous cell carcinoma. Oncoimmunology. Oct. 7, 2016;5(11):e1239005. doi: 10.1080/2162402X.2016.1239005. [cited by applicant]
Doody et al., Abstract B091: A LAG-3/PD-L1 bispecific antibody inhibits tumor growth in two syngeneic colon carcinoma models. Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science … [cited by applicant]
Doody, An anti-murine LAG-3/PD-L1 bispecific antibody which modulates T cell activity and inhibits tumour growth. Oral Presentation at 2nd Annual Advances in Immuno-Oncology Congress. May 16, 2017. 17 pages. PDR188. [cited by applicant]
Doody, In vivo Efficacy of bispecific antibodies targeting two immune-modulatory receptors. Oral Presentation at PEGS Europe. Nov. 4, 2016. 16 pages. PDR144. [cited by applicant]
Everett et al., A LAG-3/PD-L1 bispecific antibody inhibits tumour growth in two syngeneic colon carcinoma models. Poster Presentation. AACR Tumor Immunology and Immunotherapy. Oct. 21, 2016. 1 page. PDR137. [cited by applicant]
Everett et al., Abstract PR06: A LAG-3/PD-L1 bispecific antibody inhibits tumour growth in two syngeneic colon carcinoma models. AACR Special Conference on Tumor Immunology and Immunotherapy. Oct. 20-23, 2016. Boston, M… [cited by applicant]
Everett, A LAG-3/PD-L1 Bispecific Antibody Inhibits Tumour Growth in Two Syngeneic Colon Carcinoma Models. Oral Presentation at AACR Tumor Immunology and Immunotherapy. Boston, MA. Oct. 20-23, 2016. 5 pages. PDR141. [cited by applicant]
Fiehler, Development of an anti-PD-L1 Fcab. Presentation. European Antibody Congress. Oct. 29, 2018. 26 pages. PDR312. [cited by applicant]
Foy et al., Poxvirus-Based Active Immunotherapy with PD-1 and LAG-3 Dual Immune Checkpoint Inhibition Overcomes Compensatory Immune Regulation, Yielding Complete Tumor Regression in Mice. PLoS One. Feb. 24, 2016;11(2):e… [cited by applicant]
F-Star, First-in-Class Bispecific Antibodies for Cancer Immunotherapy. Jul. 2016. Presentation. 14 pages. PDR119. [cited by applicant]
Gandhi et al., Expression of LAG-3 by tumor-infiltrating lymphocytes is coincident with the suppression of latent membrane antigen-specific CD8+ T-cell function in Hodgkin lymphoma patients. Blood. Oct. 1, 2006;108(7):2… [cited by applicant]
Gliddon, Pushing all the buttons: innovating in immuno-oncology with mAb. Oral Presentation at Phacilitate Immunotherapy World 2017. Jan. 18, 2017. 11 pages. PDR165. [cited by applicant]
Grosso et al., Programmed death-ligand 1 (PD-L1) expression in various tumor types. J Immunother Cancer. 2013;1(Suppl 1):P53. http://www.immunotherapyofcancer.org/content/1/S1/P53. 1 page. [cited by applicant]
Haines et al., Abstract 4714: Blockade of LAG-3 amplifies immune activation signatures and augments curative antitumor responses to anti-PD-1 therapy in immune competent mouse models of cancer. Proceedings: AACR Annual … [cited by applicant]
Herbst et al., Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature. Nov. 27, 2014;515(7528):563-7. doi: 10.1038/nature14011. Author Manuscript. [cited by applicant]
Hid Cadena et al., Checks and Balances in Autoimmune Vasculitis. Front Immunol. Feb. 22, 2018;9:315. doi: 10.3389/fimmu.2018.00315. [cited by applicant]
Horn et al., CD3xPDL1 bi-specific T cell engager (BiTE) simultaneously activates T cells and NKT cells, kills PDL1+ tumor cells, and extends the survival of tumor-bearing humanized mice. Oncotarget. Aug. 3, 2017;8(35):5… [cited by applicant]
Huang et al., Abstract PR03: Combinatorial blockade of PD-1, CTLA-4, and LAG-3 pathways inhibits murine ovarian tumor growth. Abstracts: AACR Special Conference: Advances in Ovarian Cancer Research: Exploiting Vulnerabi… [cited by applicant]
Iwai et al., Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade. Proc Natl Acad Sci U S A. Sep. 17, 2002;99(19):12293-7. doi: 10.1073/pnas.192461099. Epub… [cited by applicant]
Jochems et al., Analyses of functions of an anti-PD-L1/TGFBR2 bispecific fusion protein (M7824). Oncotarget. Sep. 8, 2017;8(43):75217-75231. doi: 10.18632/oncotarget.20680. [cited by applicant]
Kehry et al., Abstract 271: Targeting PD-1, TIM-3 and LAG-3 in combination for improved immunotherapy combinations. AACR 106th Annual Meeting. Apr. 18-22, 2015. Philadelphia, PA. doi: 10.1158/1538-7445.AM2015-271. 8 pag… [cited by applicant]
Klooster et al., Abstract B088: Generation of immuno-modulatory receptor binding bispecific antibodies to modulate tumor immunity. Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Sci… [cited by applicant]
Koopmans et al., A novel bispecific antibody for EGFR-directed blockade of the PD-1/PD-L1 immune checkpoint. Oncoimmunology. May 31, 2018;7(8):e1466016. doi: 10.1080/2162402X.2018.1466016. [cited by applicant]
Kraman et al., A LAG-3/PD-L1 bispecific antibody inhibits tumour growth in two syngeneic colon carcinoma models. Poster Presentation. BSI/NVVI Congress. Dec. 6, 2016. 1 page. PDR153. [cited by applicant]
Kraman et al., A LAG-3/PD-L1 bispecific antibody inhibits tumour growth in two syngeneic colon carcinoma models. Abstract B091. Poster Presentation. CRI-CIMT-EATI-AACR Cancer Immunotherapy Conference. Sep. 26, 2016. 1 p… [cited by applicant]
Kraman et al., A LAG-3/PD-L1 bispecific antibody inhibits tumour growth in two syngeneic colon carcinoma models. Poster 003. Poster Presentation. 2nd Annual Advances in Immuno-Oncology Congress. May 15, 2017. 1 page. PD… [cited by applicant]
Kraman et al., A LAG-3/PD-L1 bispecific antibody inhibits tumour growth in two syngeneic colon carcinoma models. Poster 1103. Poster Presentation. Keystone Symposium—Cancer Immunology and Immunotherapy. Mar. 19, 2017. 1… [cited by applicant]
Kraman et al., A LAG-3/PD-L1 bispecific antibody inhibits tumour growth in two syngeneic colon carcinoma models. Poster 128. Poster Presentation at SITC. Nov. 9, 2016. 1 page. PDR143. [cited by applicant]
Kraman et al., A LAG-3/PD-L1 bispecific antibody inhibits tumour growth in two syngeneic colon carcinoma models. Poster 5651. Poster Presentation. AACR Annual Meeting. Apr. 1, 2017. 1 page. PDR176. [cited by applicant]
Kraman et al., A LAG-3/PD-L1 bispecific antibody inhibits tumour growth in two syngeneic colon carcinoma models. Poster Presentation. International Conference on Human & Translational Immunology. Sep. 16, 2016. 1 page. … [cited by applicant]
Kraman et al., A LAG-3/PD-L1 bispecific antibody inhibits tumour growth in two syngeneic colon carcinoma models. Poster 3005. Poster Presentation. Keystome Symposium—Biobetters and Next-Generation Biologics. Jan. 22-26,… [cited by applicant]
Kraman et al., Abstract 5651:A LAG-3/PD/L1 bispecific antibody inhibits tumor growth in two syngeneic colon carcinoma models. AACR Annual Meeting 2017. Apr. 1-5, 2017. Washington, DC. Doi: 10.1158/1538-7445.AM2017-5651.… [cited by applicant]
La Motte-Mohs et al., Abstract 3217: MGD013, a bispecific PD-1 x LAG-3 Dual-Affinity Re-Targeting (DART®) protein with T-cell immunomodulatory activity for cancer treatment. AACR 107th Annual Meeting. Apr. 16-20, 2016. … [cited by applicant]
La Motte-Mohs et al., MGD013, a bispecific PD-1 x LAG-3 Dual-Affinity Re-Targeting (DART®) protein with T-cell immunomodulatory activity for cancer treatment. Poster Presentation. 2016. http://ir.macrogenics.com/events.… [cited by applicant]
Larkin et al., Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma. N Engl J Med. Jul. 2, 2015;373(1):23-34. doi: 10.1056/NEJMoa1504030. Epub May 31, 2015. Erratum in: N Engl J Med. Nov. 29, 2018;379(… [cited by applicant]
Liu et al., Dual Targeting of Innate and Adaptive Checkpoints on Tumor Cells Limits Immune Evasion. Cell Rep. Aug. 21, 2018;24(8):2101-2111. doi: 10.1016/j.celrep.2018.07.062. [cited by applicant]
McCourt et al., KY1055; a novel ICOS/PD-L1 bispecific antibody, enhance T cell activation and delivers potent monotherapy anti-tumour response in vivo. Abstract. CIMT 2018. Feb. 28, 2018. 1 page. PDR245. [cited by applicant]
McCourt et al., KY1055; a novel ICOS/PD-L1 bispecific antibody, enhance T cell activation and delivers potent monotherapy anti-tumour response in vivo. Poster Presentation. CIMT Conference. May 9, 2018. 1 page. PDR 264. [cited by applicant]
McCourt et al., KY1055; a novel ICOS/PD-L1 bispecific antibody, enhance T cell activation and delivers potent monotherapy anti-tumour response in vivo. Presentation. CIMT Conference. May 9, 2018. 13 pages. PDR265. [cited by applicant]
Munoz-Olaya, Development of an anti-PD-L1 Fcab. Presentation. PEGS Lisbon. Nov. 16, 2018. 24 pages. PDR321. [cited by applicant]
Pavlidou et al., Simultaneous costimulatory T-cell engagement and checkpoint inhibition by PRS-344/ONC0055, a 4-1BB/PD-L1 bispecific compound for tumor localized activation of the immune system. SITC 2018. Poster Presen… [cited by applicant]
Powles et al., MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer. Nature. Nov. 27, 2014;515(7528):558-62. doi: 10.1038/nature13904. [cited by applicant]
Sainson et al., KY1055, a novel ICOS/PD-L1 bispecific antibody, efficiently enhances T cell activation and delivers a potent anti-tumour response in vivo. Abstract. AACR. Jan. 22, 2018. 1 page. PDR236. [cited by applicant]
Sainson et al., KY1055, a novel ICOS/PD-L1 bispecific antibody, efficiently enhances T cell activation and delivers a potent anti-tumour response in vivo. Poster Presentation. AACR 2018. Apr. 4, 2018. 1 page. PDR254. [cited by applicant]
Strauss et al., Phase I Trial of M7824 (MSB0011359C), a Bifunctional Fusion Protein Targeting PD-L1 and TGFβ, in Advanced Solid Tumors. Clin Cancer Res. Mar. 15, 2018;24(6):1287-1295. doi: 10.1158/1078-0432.CCR-17-2653.… [cited by applicant]
Tuna, Identification of a PD-L1 binding FCAB: a potent inhibitor of immunosuppressive signals. Abstract. European Antibody Congress. May 3, 2018. 1 page. PDR270. [cited by applicant]
Tuna, The use of bispecific antibodies to modulate anti-tumour immune responses. Oral Presentation at 10th Annual Proteins and Antibodies Congress. Apr. 24, 2017. 26 pages. PDR183. [cited by applicant]
Weismann, A LAG-3/PD-L1 Bispecific Antibody Inhibits Tumour Growth In Two Syngeneic Colon Carcinoma Models. International Conference on Human and Translational Immunology. Rhodes, Greece. Sep. 16-21, 2016. Presentation.… [cited by applicant]
Wherry, T cell exhaustion. Nat Immunol. Jun. 2011;12(6):492-9. doi: 10.1038/ni.2035. [cited by applicant]
Wilton, KY1055, a bispecific mAb2 targeting ICOS and PD-L1. Presentation. Feb. 21, 2018. 17 pages. PDR238. [cited by applicant]
Wolchok et al., Nivolumab plus ipilimumab in advanced melanoma. N Engl J Med. Jul. 11, 2013;369(2):122-33. doi: 10.1056/NEJMoa1302369. Epub Jun. 2, 2013. Erratum in: N Engl J Med. Nov. 29, 2018;379(22):2185. Author Manu… [cited by applicant]
Woo et al., Immune inhibitory molecules LAG-3 and PD-1 synergistically regulate T-cell function to promote tumoral immune escape. Cancer Res. Feb. 15, 2012;72(4):917-27. doi: 10.1158/0008-5472.CAN-11-1620. Epub Dec. 20,… [cited by applicant]
Workman et al., Negative regulation of T cell homeostasis by lymphocyte activation gene-3 (CD223). J Immunol. Jan. 15, 2005;174(2):688-95. doi: 10.4049/jimmunol.174.2.688. [cited by applicant]
Workman et al., The CD4-related molecule, LAG-3 (CD223), regulates the expansion of activated T cells. Eur J Immunol. Apr. 2003;33(4):970-9. doi: 10.1002/eji.200323382. [cited by applicant]
Wydro, Bispecific antibodies: new opportunities for novel therapies. Oral Presentation at 7th Annual Biologics Symposium. Mar. 1, 2017. 24 pages. PDR172. [cited by applicant]
Wykes et al., Immune checkpoint blockade in infectious diseases. Nat Rev Immunol. Feb. 2018;18(2):91-104. doi: 10.1038/nri.2017.112. Epub Oct. 9, 2017. [cited by applicant]
Zhang et al., Structural basis of a novel PD-L1 nanobody for immune checkpoint blockade. Cell Discov. Mar. 7, 2017;3:17004. doi: 10.1038/celldisc.2017.4. [cited by applicant]
[No Author Listed], FS118 First in Human Study in Patients With Advanced Malignancies. Sponsored by F-star Therapeutics Limited. Clinical Trial. Retreived from https://clinicaltrials.gov/ct2/show/NCT03440437. Feb. 22, 2… [cited by applicant]
Asgarov et al., A new anti-mesothelin antibody targets selectively the membrane-associated form. MAbs. Apr. 2017;9(3):Supplementary Data. doi: 10.1080/19420862.2017.1288770. 6 pages. [cited by applicant]
Awuah et al., Reduced Shedding of Surface Mesothelin Improves Efficacy of Mesothelin-Targeting Recombinant Immunotoxins. Mol Cancer Ther. Jul. 2016;15(7):1648-55. doi: 10.1158/1535-7163.MCT-15-0863. Epub May 18, 2016. [cited by applicant]
Callahan et al., Targeting T Cell Co-receptors for Cancer Therapy. Immunity. May 17, 2016;44(5):1069-78. doi: 10.1016/j.immuni.2016.04.023. [cited by applicant]
Chatterjee et al., Noninvasive Imaging of Immune Checkpoint Ligand PD-L1 in Tumors and Metastases for Guiding Immunotherapy. Mol Imaging. Dec.-Jan. 2017; 16:1536012117718459. doi: 10.1177/1536012117718459. 5 pages. [cited by applicant]
Chu et al., An Update on Anti-CD137 Antibodies in Immunotherapies for Cancer. Int J Mol Sci. Apr. 12, 2019;20(8):1822. doi: 10.3390/ijms20081822. 17 pages. [cited by applicant]
Del Bano et al., A Bispecific Antibody-Based Approach for Targeting Mesothelin in Triple Negative Breast Cancer. Front Immunol. Jul. 10, 2019;10:1593. doi: 10.3389/fimmu.2019.01593. [cited by applicant]
El-Khoueiry et al., The relationship of pharmacodynamics (PD) and pharmacokinetics (PK) to clinical outcomes in a phase I study of OX40 agonistic monoclonal antibody (mAb) PF-04518600 (PF-8600). J Clin Oncol. May 20, 20… [cited by applicant]
Faroudi et al., Abstract 2399: LAG-3/PD-L1 mAb2 can overcome PD-L1-mediated compensatory upregulation of LAG-3 induced by single-agent checkpoint blockade. Proceedings: AACR Annual Meeting 2019; Mar. 29-Apr. 3, 2019. At… [cited by applicant]
Faroudi et al., Abstract B009: FS118, a LAG-3/PD-L1 bispecific antibody, capable of driving potent anti-tumour immune responses and overcome PD-(L)1-mediated compensatory. Sep. 25-28, 2019. Fifth CRI-CIMT-EATI-AACR Inte… [cited by applicant]
Faroudi et al., FS118, a LAG-3/PD-L1 bispecific antibody, capable of driving potent anti-tumour immune responses and overcome PD-(L)1-mediated compensatory. Sep. 25-28, 2019. Poster. Fifth CRI-CIMT-EATI-AACR Internation… [cited by applicant]
Frenzel et al., Phage display-derived human antibodies in clinical development and therapy. MAbs. Oct. 2016;8(7):1177-1194. doi: 10.1080/19420862.2016.1212149. Epub Jul. 14, 2016. [cited by applicant]
F-Star, Next-Generation Bispecifics for Cancer Immunotherapy. Feb. 2020. Presented on Mar. 11, 2020 at Immuno-Oncology Summit Europe 2020. London. 46 pages. [cited by applicant]
F-Star, Redirecting T Cells. Overcoming Cancer. Improving Lives. Oct. 2019 Presentation in Investor Meeting. 36 pages. [cited by applicant]
F-Star, Redirecting T Cells. Overcoming Cancer. Improving Lives. Apr. 2020 Presentation in Investor Meeting. 43 pages. [cited by applicant]
F-Star, Redirecting T Cells. Overcoming Cancer. Improving Lives. Jan. 2020 Presentation in Investor Meeting. 41 pages. [cited by applicant]
Gaspar et al., FS120 mAb2, a dual agonist bispecific antibody targeting OX40 and CD137, activates T cells in vitro and induces FcyR-independent anti-tumour activity. SITC 2018. Nov. 7, 2018. Poster. 10 pages. [cited by applicant]
Gaspar, FS120 mAb2, a dual agonist bispecific antibody targeting OX40 and CD137. SITC 2018. Nov. 11, 2018. Presentation. 12 pages. [cited by applicant]
Geuijen et al., Abstract 541: An unbiased screen identifies a CD137xPD-L1 bispecific IgG1 antibody with unique T cell activation and binding properties. Cancer Res. 2019;79(13_Supplement):541. Poster Presentation AACR C… [cited by applicant]
Glisson et al., Phase 1 study of MEDI0562, a humanized OX40 agonist monoclonal antibody (mAb), in adult patients (pts) with advanced solid tumors. Annals Onocol. Oct. 1, 2016;27(6):vi361. doi: 10.1093/annonc/mdw378.07. [cited by applicant]
Gunde et al., Abstract 1532: A novel, monovalent tri-specific antibody-based molecule that simultaneously modulates PD-L1 and 4-1BB exhibits potent anti-tumoral activity in vivo. Cancer Res. 2019;79(13_Supplement):1532.… [cited by applicant]
Hassan et al., Mesothelin Immunotherapy for Cancer: Ready for Prime Time? J Clin Oncol. Dec. 2016;34(34):4171-4179. doi: 10.1200/JCO.2016.68.3672. Epub Oct. 31, 2016. [cited by applicant]
Hassan et al., Phase II clinical trial of amatuximab, a chimeric antimesothelin antibody with pemetrexed and cisplatin in advanced unresectable pleural mesothelioma. Clin Cancer Res. Dec. 1, 2014;20(23):5927-36. doi: 10… [cited by applicant]
Hebb et al., Administration of low-dose combination anti-CTLA4, anti-CD137, and anti-OX40 into murine tumor or proximal to the tumor draining lymph node induces systemic tumor regression. Cancer Immunol Immunother. Jan.… [cited by applicant]
Ho et al., A novel high-affinity human monoclonal antibody to mesothelin. Int J Cancer. May 1, 2011;128(9):2020-30. doi: 10.1002/ijc.25557. [cited by applicant]
Kraman et al., Dual blockade of PD-L1 and LAG-3 with FS118, a unique bispecific antibody, induces CD8+ T-cell activation and modulates the tumour microenvironment to promote anti-tumour immune responses. Apr. 14-18, 201… [cited by applicant]
Kraman et al., Dual blockade of PD-L1 and LAG-3 with FS118, a unique bispecific antibody, induces T-cell activation with the potential to drive potent anti-tumour immune responses. Nov. 7, 2017;5 Suppl 2 (87):Abstract P… [cited by applicant]
Kraman et al., Dual blockade of PD-L1 and LAG-3 with FS118, a unique bispecific antibody, induces T-cell activation with the potential to drive potent anti-tumour immune responses. Apr. 14-18, 2018;78(13 Suppl);Abstract… [cited by applicant]
Kraman et al., Dual blockade of PD-L1 and LAG-3 with FS118, a unique bispecific antibody, induces T-cell activation with the potential to drive potent anti-tumour immune responses. Poster P348. 32nd Annual Meeting and P… [cited by applicant]
Kraman et al., FS118, a Bispecific Antibody Targeting LAG-3 and PD-L1, Enhances T-Cell Activation Resulting in Potent Antitumor Activity. Clin Cancer Res. Jul. 1, 2020;26(13):3333-3344. doi: 10.1158/1078-0432.CCR-19-354… [cited by applicant]
Kunik et al., Structural consensus among antibodies defines the antigen binding site. PLoS Comput Biol. 2012;8(2):e1002388. doi: 10.1371/journal.pcbi.1002388. Epub Feb. 23, 2012. 12 pages. [cited by applicant]
Kvarnhammar et al., The CTLA-4 x OX40 bispecific antibody ATOR-1015 induces anti-tumor effects through tumor-directed immune activation. J Immunother Cancer. Apr. 11, 2019;7(1):103. doi: 10.1186/s40425-019-0570-8. [cited by applicant]
Lakins et al., FS222 mAb2, a bispecific conditional agonist antibody targeting CD137 and PD-L1, induces potent lymphocyte activation and has a favourable safety profile. F-star, Cambridge, UK. Poster Presentation. AACR … [cited by applicant]
Lakins et al., Optimising TNFRSF agonism and checkpoint blockade with a novel CD137/PD-L1 bispecific antibody. Abstracts Therapeutic Development. Dec. 1, 2018;29(Supplement 10):X30. doi: 10.1093/annonc/mdy487.014. 1 pag… [cited by applicant]
Levitan, Amgen Halts Rilotumumab Development Due to Increased Death Signal. Cancer Network. Nov. 26, 2014. Retrieved from www.cancernetwork.com/view/amgen-halts-rilotumumab-development-due-increased-death-signal. 3 page… [cited by applicant]
Li et al., Discovery and preclinical characterization of the antagonist anti-PD-L1 monoclonal antibody LY3300054. J Immunother Cancer. Apr. 30, 2018;6(1):31. doi: 10.1186/s40425-018-0329-7. Erratum in: J Immunother Canc… [cited by applicant]
Ma et al., Recognition of mesothelin by the therapeutic antibody MORAb-009: structural and mechanistic insights. J Biol Chem. Sep. 28, 2012;287(40):33123-31. doi: 10.1074/jbc.M112.381756. Epub Jul. 11, 2012. [cited by applicant]
Mayes et al., Abstract 539: A bispecific Fc-silenced IgG1 antibody (MCLA-145) requires PD-L1 binding to activate CD137. Cancer Res. 2019;79(13_Supplement):539. AACR Presentation 2019. Jul. 1, 2019. doi: 10.1158/1538-744… [cited by applicant]
McCourt, Development of an ICOS/PD-L1 Bispecific, Mar. 18-22, 2019. Abstract. Cambridge Healthtech Institute's 4th Annual Immuno-Oncology Summit Europe 2019 (London). [cited by applicant]
Melero et al., Clinical development of immunostimulatory monoclonal antibodies and opportunities for combination. Clin Cancer Res. Mar. 1, 2013;19(5):997-1008. doi: 10.1158/1078-0432.CCR-12-2214. [cited by applicant]
Perez-Ruiz et al., Anti-CD137 and PD-1/PD-L1 Antibodies En Route toward Clinical Synergy. Clin Cancer Res. Sep. 15, 2017;23(18):5326-5328. doi: 10.1158/1078-0432.CCR-17-1799. Epub Aug. 8, 2017. [cited by applicant]
Poon et al., Dual agonist bispecific antibody targeting OX40 and DC137 mediates anti-tumour immunity and synergises with PD-1/PD-L1 blockade to improve survival in a syngeneic mouse model. AACR 2019. Mar. 29, 2019. Post… [cited by applicant]
Ryan et al., A novel biologic platform elicits profound T cell costimulatory activity and antitumor immunity in mice. Cancer Immunol Immunother. Apr. 2018;67(4):605-613. doi: 10.1007/s00262-018-2116-1. Epub Jan. 11, 201… [cited by applicant]
Tang et al., A human single-domain antibody elicits potent antitumor activity by targeting an epitope in mesothelin close to the cancer cell surface. Mol Cancer Ther. Apr. 2013;12(4):416-26. doi: 10.1158/1535-7163.MCT-1… [cited by applicant]
Tuna, Delivering the next immuno-oncology breakthrough. PEGS Europe 2018. Nov. 11, 2018. Presentation. 24 pages. [cited by applicant]
Yap et al., A first-in-human phase I study of FS118, an anti-LAG-3/PD-L1 bispecific antibody in patients with solid tumors that have progressed on prior PD-1/PD-L1 therapy. Journal of Clinical Oncology. Jun. 1, 2019. Po… [cited by applicant]
Yap et al., A first-in-human phase I study of FS118, an anti-LAG-3/PD-L1 bispecific antibody in patients with solid tumors that have progressed on prior PD-1/PD-L1 therapy. Journal of Clinical Oncology. May 26, 2019;37(… [cited by applicant]
Yap et al., Abstract TPS2652: A first-in-human phase I study of FS118, an anti-LAG-3/PD-L1 bispecific antibody in patients with solid tumors that have progressed on prior PD-1/PD-L1 therapy. Journal of Clinical Oncology… [cited by applicant]
Yonezawa et al., Boosting Cancer Immunotherapy with Anti-CD137 Antibody Therapy. Clin Cancer Res. Jul. 15, 2015;21(14):3113-20. doi: 10.1158/1078-0432.CCR-15-0263. Epub Apr. 23, 2015. [cited by applicant]
Zhao et al., Novel Antibody Therapeutics Targeting Mesothelin In Solid Tumors. Clin Cancer Drugs. Oct. 2016;3(2):76-86. doi: 10.2174/2212697X03666160218215744. [cited by applicant]
International Search Report and Written Opinion for Application No. PCT/EP2019/068800, mailed Nov. 5, 2019. [cited by applicant]
International Preliminary Report on Patentability for Application No. PCT/EP2019/068800, mailed Jan. 21, 2021. [cited by applicant]
[No Author Listed] F-star Alpha: A new asset centric company. Retrieved from http://www.onenucleus.com/media/Events/LSLS/11%20feb%202014/Jane%20Dancer.pdf on Jan. 8, 2015. 15 pages. [cited by applicant]
Asgarov et al., A new anti-mesothelin antibody targets selectively the membrane-associated form. MAbs. Apr. 2017;9(3):567-577. doi: 10.1080/19420862.2017.1288770. [cited by applicant]
Bacac et al., Abstract 1494: CEA TCB: A novel head-to-tail 2:1 T cell bispecific antibody for treatment of CEA-positive solid tumors. Oncoimmunology. Aug. 2016; 5(Abstract): e1203498. Epub Jun. 24, 2016. doi: 10.1080/21… [cited by applicant]
Chester et al., 4-1BB agonism: adding the accelerator to cancer immunotherapy. Cancer Immunol Immunother. Oct. 2016;65(10):1243-8. doi: 10.1007/s00262-016-1829-2. Epub Mar. 31, 2016. [cited by applicant]
Chester et al., Dual antibody therapy to harness the innate anti-tumor immune response to enhance antibody targeting of tumors. Curr Opin Immunol. Apr. 2015;33:1-8. doi: 10.1016/j.coi.2014.12.010. Epub Jan. 7, 2015. [cited by applicant]
Goding et al., Combination of adoptive cell transfer, anti-PD-L1 and anti-LAG-3 antibodies for the treatment of recurrent tumors: better with more. OncoImmunology. Oct. 22, 2013;2(8):e25050-1-e25050-3. [cited by applicant]
Hasenhindl et al., Creating stable stem regions for loop elongation in Fcabs—insights from combining yeast surface display, in silico loop reconstruction and molecular dynamics simulations. Biochim Biophys Acta. 2014;18… [cited by applicant]
Hasenhindl et al., Stability assessment on a library scale: a rapid method for the evaluation of the commutability and insertion of residues in C-terminal loops of the CH3 domains of IgG1-Fc. Protein Eng Des Sel. 2013;2… [cited by applicant]
Jing et al., Combined immune checkpoint protein blockade and low dose whole body irradiation as immunotherapy for myeloma. Journal of Immunotherapy of Cancer. doi: 10.1186/S40425-014-0043-Z. Jan. 20, 2015. 15 pages. [cited by applicant]
Kraman et al., A LAG-3/PD-L1 bispecific antibody inhibits tumor growth in two syngeneic colon carcinoma models. Journal of ImmunoTherapy of Cancer. 2016;4(Suppl 1):82(abstract P124). [cited by applicant]
Kraman et al., A LAG-3/PD-L1 bispecific antibody inhibits tumor growth in two syngeneic colon carcinoma models. Retrieved from http://www.f-star.com/media/73722/A-LAG-3-PD-L1-bispecific-antibody-inhibits-tumour-growth-i… [cited by applicant]
Lakins et al., A Novel CD137/PD-L1 Bispecific Antibody Modulates the Tumour Microenvironmentby Activating CD8+ T cells and Results in Tumour Growth Inhibition. F-Star Poster. Nov. 7, 2018. 1 page. Retrieved from https:/… [cited by applicant]
Lee et al., 4-1BB and OX40 dual costimulation synergistically stimulate primary specific CD8 T cells for robust effector function. J Immunol. Sep. 1, 2004;173(5):3002-12. doi: 10.4049/jimmunol.173.5.3002. [cited by applicant]
Leung et al., A HER2-specific Modified Fc Fragment (Fcab) Induces Antitumor Effects Through Degradation of HER2 and Apoptosis. Mol Ther. Nov. 2015;23(11):1722-1733. doi: 10.1038/mt.2015.127. Epub Aug. 3, 2015. Erratum i… [cited by applicant]
Lobner et al., Engineered IgG1-Fc—one fragment to bind them all. Immunol Rev. Mar. 2016;270(1):113-31. doi: 10.1111/imr.12385. [cited by applicant]
Lobner et al., Two-faced Fcab prevents polymerization with VEGF and reveals thermodynamics and the 2.15 Å crystal structure of the complex. MAbs. Oct. 2017;9(7):1088-1104. doi: 10.1080/19420862.2017.1364825. Epub Aug. 1… [cited by applicant]
Lundqvist et al., 31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016): Part One. Journal for Immunotherapy of Cancer. Nov. 16, 2016;4(1):74(abstract P124). [cited by applicant]
Qui et al., CD134 plus CD137 dual costimulation induces Eomesodermin in CD4 T cells to program cytotoxic Th1 differentiation. J Immunol. Oct. 1, 2011;187(7):3555-64. doi: 10.4049/jimmunol.1101244. Epub Aug. 31, 2011. [cited by applicant]
Ramelet et al., Beneficial outcome of combination therapy with 4-1BB targeting antibody. Eur J Cancer. Nov. 29, 2016;69(Suppl 1):S96-S97. [cited by applicant]
Sallin et al., The anti-lymphoma activities of anti-CD137 monoclonal antibodies are enhanced in FcγRIII(−/−) mice. Cancer Immunol Immunother. Sep. 2014;63(9):947-58. doi: 10.1007/s00262-014-1567-2. Epub Jun. 14, 2014. [cited by applicant]
Schlothauer et al., Novel human IgG1 and IgG4 Fc-engineered antibodies with completely abolished immune effector functions. Protein Eng Des Sel. Oct. 2016;29(10):457-466. doi: 10.1093/protein/gzw040. Epub Aug. 29, 2016. [cited by applicant]
Shindo et al., Combination immunotherapy with 4-1BB activation and PD-1 blockade enhances antitumor efficacy in a mouse model of subcutaneous tumor. Anticancer Res. Jan. 2015;35(1):129-36. [cited by applicant]
Vilgelm et al., Combinatorial approach to cancer immunotherapy: strength in numbers. Journal of Leukocyte Biology. 2016;100(2):275-90. Epub Jun. 2, 2016. [cited by applicant]
Wozniak-Knopp et al., Designing Fcabs: well-expressed and stable high affinity antigen-binding Fc fragments. Protein Eng Des Sel. Sep. 1, 2017;30(9):657-671. doi: 10.1093/protein/gzx042. [cited by applicant]
Wozniak-Knopp et al., Introducing antigen-binding sites in structural loops of immunoglobulin constant domains: Fc fragments with engineered HER2/neu-binding sites and antibody properties. Protein Eng Des Sel. 2010;23(4… [cited by applicant]
Xu et al., In vitro characterization of five humanized OKT3 effector function variant antibodies. Cell Immunol. Feb. 2, 20005;200(1):16-26. [cited by applicant]
U.S. Appl. No. 16/955,450, filed Jun. 18, 2020, Tuna et al. [cited by applicant]
U.S. Appl. No. 17/259,634, filed Jan. 12, 2021, Munoz-Olaya et al. [cited by applicant]
U.S. Appl. No. 17/259,680, filed Jan. 12, 2021, Pechouckova et al. [cited by applicant]
U.S. Appl. No. 17/259,754, filed Jan. 12, 2021, Lakins et al. [cited by applicant]
U.S. Appl. No. 17/259,642, filed Jan. 12, 2021, Wollerton et al. [cited by applicant]
U.S. Appl. No. 17/259,714, filed Jan. 12, 2021, Tuna et al. [cited by applicant]
U.S. Appl. No. 17/259,791, filed Jan. 12, 2021, Lakins et al. [cited by applicant]
U.S. Appl. No. 17/259,796, filed Jan. 12, 2021, Tuna et al. [cited by applicant]
PCT/EP2019/068800, Nov. 5, 2019, International Search Report and Written Opinion. [cited by applicant]
PCT/EP2019/068800, Jan. 21, 2021, International Preliminary Report on Patentability. [cited by applicant]
Dahlén et al., Bispecific antibodies in cancer immunotherapy. Ther Adv Vaccines Immunother. Feb. 2018;6(1):3-17. doi: 10.1177/2515135518763280. Epub Mar. 28, 2018. [cited by applicant]
Golfier et al., Anetumab ravtansine: a novel mesothelin-targeting antibody-drug conjugate cures tumors with heterogeneous target expression favored by bystander effect. Mol Cancer Ther. Jun. 2014;13(6):1537-48. doi: 10.… [cited by applicant]
Schroeder, Chapter 13: Immunoglobulins and Their Genes. From Arthritis and Allied Conditions: A Textbook of Rheumatology. 15th Ed. vol 1. Eds Koopman et al.Lippincot Williams & Wilkins. pp. 289-304. Supplied by the Brit… [cited by applicant]
[No Author Listed], mesothelin isoform 1 preproprotein [ [cited by applicant]
[No Author Listed], mesothelin isoform 1 preproprotein [Mus musculus]. NCBI Reference Sequence: NP_001343215.1. Jun. 18, 2024. Retrieved from https://www.ncbi.nlm.nih.gov/protein/NP_001343215.1. 3 pages. [cited by applicant]
[No Author Listed], Molecular biological basis of immunotherapy. New and Orphan Drugs for Leukemia Therapeutics. Sep. 30, 2016. 387-390. Retrieved on Dec. 18, 2023. 7 pages. [cited by applicant]
[No Author Listed], Predicted: mesothelin isoform X4 [Macaca fascicularis]. NCBI Reference Sequence: XP_005590874.2. Jan. 25, 2016. Retrieved from https://www.ncbi.nlm.nih.gov/protein/XP_005590874.2. 2 pages. [cited by applicant]
[No Author Listed], tumor necrosis factor receptor superfamily member 9 precursor [ [cited by applicant]
Badri et al., Optimization of radiation dosing schedules for proneural glioblastoma. J Math Biol. Apr. 2016;72(5):1301-36. doi: 10.1007/s00285-015-0908-x. [cited by applicant]
Baylot et al., TCTP Has a Crucial Role in the Different Stages of Prostate Cancer Malignant Progression. Results Probl Cell Differ. 2017;64:255-261. doi: 10.1007/978-3-319-67591-6_13. [cited by applicant]
Chen et al., Enhancement and destruction of antibody function by somatic mutation: unequal occurrence is controlled by V gene combinatorial associations. Embo J. Jun. 15, 1995;14(12):2784-94. doi: 10.1002/j.1460-2075.19… [cited by applicant]
Cooper, The Development and Causes of Cancer. From The Cell: Molecular Approach. 2nd Ed. Sunderland, MA. Sinauer Associates. 2000. 9 pages. [cited by applicant]
Edwards et al., The remarkable flexibility of the human antibody repertoire; isolation of over one thousand different antibodies to a single protein, BLyS. J Mol Biol. Nov. 14, 2003;334(1):103-18. doi: 10.1016/j.jmb.200… [cited by applicant]
Han et al., Bispecific anti-CD3 x anti-HER2 antibody mediates T cell cytolytic activity to HER2-positive colorectal cancer in vitro and in vivo. Int J Oncol. Dec. 2014;45(6):2446-54. doi: 10.3892/ijo.2014.2663. Epub Sep… [cited by applicant]
Heppner et al., Tumor heterogeneity: biological implications and therapeutic consequences. Cancer Metastasis Rev. 1983;2(1):5-23. doi: 10.1007/BF00046903. [cited by applicant]
Koenig et al., Mutational landscape of antibody variable domains reveals a switch modulating the interdomain conformational dynamics and antigen binding. Proc Natl Acad Sci U S A. Jan. 24, 2017;114(4):E486-E495. doi: 10… [cited by applicant]
Kussie et al., A single engineered amino acid substitution changes antibody fine specificity. J Immunol. Jan. 1, 1994;152(1):146-52. [cited by applicant]
Lin et al., Fc-dependent expression of CD137 on human NK cells: insights into “agonistic” effects of anti-CD137 monoclonal antibodies. Blood. Aug. 1, 2008;112(3):699-707. doi: 10.1182/blood-2007-11-122465. Epub Jun. 2, … [cited by applicant]
Link et al., Abstract 3752: Preclinical pharmacology of MP0310: a 4-1BB/FAP bispecific DARPin drug candidate promoting tumor-restricted T-cell costimulation. Cancer Res. Jul. 1, 2018;78(13_Supplement):3752. [cited by applicant]
Liu et al., Abstract 3642: Tumor-antigen expression-dependent activation of the CD137 costimulatory pathway by bispecific DART® proteins. Cancer Res. Jul. 1, 2017;77(13_Supplement):3642. [cited by applicant]
Lo et al., Effector-attenuating Substitutions That Maintain Antibody Stability and Reduce Toxicity in Mice. J Biol Chem. Mar. 3, 2017;292(9):3900-3908. doi: 10.1074/jbc.M116.767749. Epub Jan. 11, 2017. [cited by applicant]
Muller et al., Spliceosomal peptide P140 for immunotherapy of systemic lupus erythematosus: results of an early phase II clinical trial. Arthritis Rheum. Dec. 2008;58(12):3873-83. doi: 10.1002/art.24027. [cited by applicant]
Reichen et al., Abstract 3029: FAP-mediated tumor accumulation of a T-cell agonistic FAP/4-1BB DARPin drug candidate analyzed by SPECT/CT and quantitative biodistribution. Cancer Res. Jul. 1, 2018;78(13_Supplement):3029. [cited by applicant]
Seckinger et al., Development and characterization of NILK-2301, a novel CEACAM5xCD3 κλ bispecific antibody for immunotherapy of CEACAM5-expressing cancers. J Hematol Oncol. Dec. 12, 2023;16(1):117. doi: 10.1186/s13045-… [cited by applicant]
Segal et al., Results from an Integrated Safety Analysis of Urelumab, an Agonist Anti-CD137 Monoclonal Antibody. Clin Cancer Res. Apr. 15, 2017;23(8):1929-1936. doi: 10.1158/1078-0432.CCR-16-1272. Epub Oct. 18, 2016. [cited by applicant]
Shen, et al. Single variable domain-IgG fusion. A novel recombinant approach to Fc domain-containing bispecific antibodies. J Biol Chem. Apr. 21, 2006;281(16):10706-14. doi: 10.1074/jbc.M513415200. Epub Feb. 15, 2006. [cited by applicant]
Torres et al., The immunoglobulin constant region contributes to affinity and specificity. Trends Immunol. Feb. 2008;29(2):91-7. doi: 10.1016/j.it.2007.11.004. Epub Jan. 10, 2008. [cited by applicant]
Wang et al., Retargeting T cells for HER2-positive tumor killing by a bispecific Fv-Fc antibody. PLoS One. Sep. 23, 2013;8(9):e75589. doi: 10.1371/journal.pone.0075589. eCollection 2013. [cited by applicant]
Durham et al., Lymphocyte Activation Gene 3 (LAG-3) modulates the ability of CD4 T-cells to be suppressed in vivo. PLoS One. Nov. 5, 2014;9(11):e109080. doi: 10.1371/journal.pone.0109080. 13 pages. [cited by applicant]
Gide et al., Distinct Immune Cell Populations Define Response to Anti-PD-1 Monotherapy and Anti-PD-1/Anti-CTLA-4 Combined Therapy. Cancer Cell. Feb. 11, 2019;35(2):238-255.e6. doi: 10.1016/j.ccell.2019.01.003. [cited by applicant]
Gough et al., OX40 agonist therapy enhances CD8 infiltration and decreases immune suppression in the tumor. Cancer Res. Jul. 1, 2008;68(13):5206-15. doi: 10.1158/0008-5472.CAN-07-6484. [cited by applicant]
Hong et al., An Agonistic Anti-CD137 Antibody Disrupts Lymphoid Follicle Structure and T-Cell-Dependent Antibody Responses. Cell Rep Med. Jun. 23, 2020;1(3):100035. doi: 10.1016/j.xcrm.2020.100035. [cited by applicant]
Kaas et al., IG, TR and IgSF, MHC and MhcSF: what do we learn from the IMGT Colliers de Perles? Brief Funct Genomic Proteomic. Dec. 2007;6(4):253-64. doi: 10.1093/bfgp/elm032. Epub Jan. 21, 2008. [cited by applicant]
Koyama et al., Adaptive resistance to therapeutic PD-1 blockade is associated with upregulation of alternative immune checkpoints. Nat Commun. Feb. 17, 2016;7:10501. doi: 10.1038/ncomms10501. 9 pages. [cited by applicant]
Matsuzaki et al., Tumor-infiltrating NY-ESO-1-specific CD8+ T cells are negatively regulated by LAG-3 and PD-1 in human ovarian cancer. Proc Natl Acad Sci U S A. Apr. 27, 2010;107(17):7875-80. doi: 10.1073/pnas.10033451… [cited by applicant]
Otano et al., CD137 (4-1BB) costimulation of CD8+ T cells is more potent when provided in cis than in trans with respect to CD3-TCR stimulation. Nat Commun. Dec. 15, 2021;12(1):7296. doi: 10.1038/s41467-021-27613-w. [cited by applicant]
Shepherd et al., T Cell Immunity to Bacterial Pathogens: Mechanisms of Immune Control and Bacterial Evasion. Int J Mol Sci. Aug. 26, 2020;21(17):6144. doi: 10.3390/ijms21176144. [cited by applicant]
Turaj et al., Augmentation of CD134 (OX40)-dependent NK anti-tumour activity is dependent on antibody cross-linking. Sci Rep. Feb. 2, 2018;8(1):2278. doi: 10.1038/s41598-018-20656-y. [cited by applicant]
Ye et al., CD137, an attractive candidate for the immunotherapy of lung cancer. Cancer Sci. May 2020;111(5):1461-1467. doi: 10.1111/cas.14354. Epub Apr. 3, 2020. [cited by applicant]
Yuan et al., Contributions of Costimulatory Molecule CD137 in Endothelial Cells. J Am Heart Assoc. Jun. 2021;10(11):e020721. doi: 10.1161/JAHA.120.020721. Epub May 22, 2021. [cited by applicant]