Granted Patent
B2
US 12,312,403 · App. 18/175,420 · Granted May 27, 2025
Antibodies against TIM3 and uses thereof
Inventors:
Xiao Min Schebye (San Carlos, CA); Mark J. Selby (San Francisco, CA); Michelle Minhua Han (Piedmont, CA); Christine Bee (San Francisco, CA); Andy X. Deng (San Mateo, CA); Anan Chuntharapai (Daly City, CA); Brigitte Devaux (Palo Alto, CA); Huiming Li (Lexington, MA); Paul O. Sheppard (Granite Falls, WA); Alan J. Korman (Piedmont, CA); Daniel F. Ardourel (Woodinville, WA); Ekaterina Deyanova (Lawrenceville, NJ); Richard Huang (Bridgewater, NJ); Guodong Chen (East Brunswick, NJ); Michelle Kuhne (San Francisco, CA); Hong-An Truong (San Francisco, CA)
Assignee:
Bristol-Myers Squibb Company
C07K16/2803A61K47/6849A61P35/00C07K16/2818C07K16/2827C07K16/2878C07K16/30C07K16/3046G01N33/57492A61K2039/505A61K2039/507C07K2317/21C07K2317/24C07K2317/31C07K2317/33C07K2317/34C07K2317/41C07K2317/52C07K2317/55C07K2317/56C07K2317/565C07K2317/71C07K2317/732C07K2317/734C07K2317/74C07K2317/76C07K2317/92C07K2317/94
View Patent ↗
Loading inventors, assignments & file history…
Abstract
Provided herein are antibodies, or antigen-binding portions thereof, that bind to T-cell immunoglobulin and mucin-domain containing-3 (TIM3) protein. Also provided are uses of these antibodies, or antigen-binding portions thereof, in therapeutic applications, such as treatment of cancer. Further provided are cells that produce the antibodies, or antigen-binding portions thereof, polynucleotides encoding the heavy and/or light chain regions of the antibodies, or antigen-binding portions thereof, and vectors comprising the polynucleotides encoding the heavy and/or light chain regions of the antibodies, or antigen-binding portions thereof.
Claims (23)
1. A method of stimulating an immune response in a subject, comprising administering to the subject an antibody that binds to human T-cell immunoglobulin and mucin-domain containing-3 (TIM3), wherein the antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises a heavy chain CDR1, CDR2, and CDR3 comprising the amino acid sequences set forth in SEQ ID NOs: 41, 122, and 126, respectively, and the VL comprises a light chain CDR1, CDR2, and CDR3 comprising the amino acid sequences set forth in SEQ ID NOs: 64, 66, and 68, respectively.
2. The method of claim 1 , wherein the immune response comprises an antigen-specific T cell response.
3. The method of claim 1 , wherein T cell activation is stimulated, T cell proliferation is stimulated, IFN-γ production by T cells is stimulated, or a combination thereof.
4. The method of claim 1 , wherein the subject has a tumor and an immune response against the tumor is stimulated.
5. The method of claim 1 , wherein the VH comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 364, and wherein the VL comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 60.
6. The method of claim 1 , wherein the VH comprises the amino acid sequence set forth in SEQ ID NO: 364, and wherein the VL comprises the amino acid sequence set forth in SEQ ID NO: 60.
7. The method of claim 1 , wherein
(a) the heavy chain comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 349 and the light chain comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 29;
(b) the heavy chain comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 351 and the light chain comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 29;
(c) the heavy chain comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 353 and the light chain comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 29;
(d) the heavy chain comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 350 and the light chain comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 29;
(e) the heavy chain comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 352 and the light chain comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 29; or
(f) the heavy chain comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 354 and the light chain comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 29.
8. The method of claim 1 , wherein the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 349 and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 29.
9. The method of claim 1 , wherein the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 351 and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 29.
10. The method of claim 1 , wherein the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 353 and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 29.
11. The method of claim 1 , wherein the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 350 and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 29.
12. The method of claim 1 , wherein the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 352 and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 29.
13. The method of claim 1 , wherein the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 354 and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 29.
14. The method of claim 1 , wherein the antibody is selected from the group consisting of an IgGI, an IgG2, an IgG3, an IgG4, and a variant thereof.
15. The method of claim 1 , wherein the antibody comprises an effectorless IgG1 Fc.
16. The method of claim 1 , further comprising administering one or more additional therapeutic.
17. The method of claim 16 , wherein the additional therapeutic comprises an anti-PD-1 antibody, an anti-LAG-3 antibody, an anti-CTLA-4 antibody, an anti-GITR antibody, or an anti-PD-L1 antibody.
Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Aug 25, 2023
From: SCHEBYE, XIAO MIN; SELBY, MARK J.; HAN, MICHELLE MINHUA; BEE, CHRISTINE; DENG, ANDY X.; CHUNTHARAPAI, ANAN; DEVAUX, BRIGITTE; LI, HUIMING; SHEPPARD, PAUL O.; KORMAN, ALAN J.; ARDOUREL, DANIEL F.; DEYANOVA, EKATERINA; HUANG, RICHARD; CHEN, GUODONG; KUHNE, MICHELLE; TRUONG, HONG-AN
To: BRISTOL-MYERS SQUIBB COMPANY
Reel/Frame 064708/0563 →
Continuity (6)
Provisional Application
62459499
· Feb 15, 2017
Provisional Application
62362541
· Jul 14, 2016
References Cited (397)
US 4399216A
· Axel et al.
· 1983
[cited by applicant]
US 4439196A
· Higuchi
· 1984
[cited by applicant]
US 4447224A
· Decant, Jr. et al.
· 1984
[cited by applicant]
US 4447233A
· Mayfield
· 1984
[cited by applicant]
US 4475196A
· La Zor
· 1984
[cited by applicant]
US 4486194A
· Ferrara
· 1984
[cited by applicant]
US 4487603A
· Harris
· 1984
[cited by applicant]
US 4522811A
· Eppstein et al.
· 1985
[cited by applicant]
US 4596556A
· Morrow et al.
· 1986
[cited by applicant]
US 4634665A
· Axel et al.
· 1987
[cited by applicant]
US 4683195A
· Mullis et al.
· 1987
[cited by applicant]
US 4790824A
· Morrow et al.
· 1988
[cited by applicant]
US 4816567A
· Cabilly et al.
· 1989
[cited by applicant]
US 4881175A
· Ladner
· 1989
[cited by applicant]
US 4941880A
· Burns
· 1990
[cited by applicant]
US 4946778A
· Ladner et al.
· 1990
[cited by applicant]
US 5013653A
· Huston et al.
· 1991
[cited by applicant]
US 5064413A
· McKinnon et al.
· 1991
[cited by applicant]
US 5091513A
· Huston et al.
· 1992
[cited by applicant]
US 5132405A
· Huston et al.
· 1992
[cited by applicant]
US 5179017A
· Axel et al.
· 1993
[cited by applicant]
US 5223409A
· Ladner et al.
· 1993
[cited by applicant]
US 5225539A
· Winter
· 1993
[cited by applicant]
US 5258498A
· Huston et al.
· 1993
[cited by applicant]
US 5260203A
· Ladner et al.
· 1993
[cited by applicant]
US 5312335A
· McKinnon et al.
· 1994
[cited by applicant]
US 5374548A
· Caras, I
· 1994
[cited by applicant]
US 5383851A
· McKinnon, Jr. et al.
· 1995
[cited by applicant]
US 5399163A
· Peterson et al.
· 1995
[cited by applicant]
US 5399331A
· Loughrey et al.
· 1995
[cited by applicant]
US 5403484A
· Ladner et al.
· 1995
[cited by applicant]
US 5416016A
· Low et al.
· 1995
[cited by applicant]
US 5427908A
· Dower et al.
· 1995
[cited by applicant]
US 5455030A
· Ladner et al.
· 1995
[cited by applicant]
US 5476786A
· Huston
· 1995
[cited by applicant]
US 5476996A
· Wilson et al.
· 1995
[cited by applicant]
US 5482858A
· Huston et al.
· 1996
[cited by applicant]
US 5530101A
· Queen et al.
· 1996
[cited by applicant]
US 5545806A
· Lonberg et al.
· 1996
[cited by applicant]
US 5545807A
· Surani et al.
· 1996
[cited by applicant]
US 5569825A
· Lonberg et al.
· 1996
[cited by applicant]
US 5571698A
· Ladner et al.
· 1996
[cited by applicant]
US 5580717A
· Dower et al.
· 1996
[cited by applicant]
US 5585089A
· Queen et al.
· 1996
[cited by applicant]
US 5624821A
· Winter et al.
· 1997
[cited by applicant]
US 5625126A
· Lonberg et al.
· 1997
[cited by applicant]
US 5633425A
· Lonberg et al.
· 1997
[cited by applicant]
US 5648260A
· Winter et al.
· 1997
[cited by applicant]
US 5661016A
· Lonberg et al.
· 1997
[cited by applicant]
US 5677425A
· Bodmer et al.
· 1997
[cited by applicant]
US 5693762A
· Queen et al.
· 1997
[cited by applicant]
US 5698767A
· Wilson et al.
· 1997
[cited by applicant]
US 5714350A
· Co et al.
· 1998
[cited by applicant]
US 5770429A
· Lonberg et al.
· 1998
[cited by applicant]
US 5789650A
· Lonberg et al.
· 1998
[cited by applicant]
US 5811097A
· Allison et al.
· 1998
[cited by applicant]
US 5814318A
· Lonberg et al.
· 1998
[cited by applicant]
US 5837243A
· Deo et al.
· 1998
[cited by applicant]
US 5869046A
· Presta et al.
· 1999
[cited by applicant]
US 5874299A
· Lonberg et al.
· 1999
[cited by applicant]
US 5877397A
· Lonberg et al.
· 1999
[cited by applicant]
US 5885793A
· Griffiths et al.
· 1999
[cited by applicant]
US 5922845A
· Deo et al.
· 1999
[cited by applicant]
US 5939598A
· Kucherlapati et al.
· 1999
[cited by applicant]
US 5969108A
· McCafferty et al.
· 1999
[cited by applicant]
US 6075181A
· Kucherlapati et al.
· 2000
[cited by applicant]
US 6114598A
· Kucherlapati et al.
· 2000
[cited by applicant]
US 6121022A
· Presta et al.
· 2000
[cited by applicant]
US 6150584A
· Kucherlapati et al.
· 2000
[cited by applicant]
US 6162963A
· Kucherlapati et al.
· 2000
[cited by applicant]
US 6165745A
· Ward et al.
· 2000
[cited by applicant]
US 6172197B1
· McCafferty et al.
· 2001
[cited by applicant]
US 6180370B1
· Queen et al.
· 2001
[cited by applicant]
US 6194551B1
· Idusogie et al.
· 2001
[cited by applicant]
US 6207156B1
· Kuchroo et al.
· 2001
[cited by applicant]
US 6277375B1
· Ward
· 2001
[cited by applicant]
US 6350861B1
· Co et al.
· 2002
[cited by applicant]
US 6437095B1
· Lilie et al.
· 2002
[cited by applicant]
US 6521404B1
· Griffiths et al.
· 2003
[cited by applicant]
US 6544731B1
· Griffiths et al.
· 2003
[cited by applicant]
US 6555313B1
· Griffiths et al.
· 2003
[cited by applicant]
US 6582915B1
· Griffiths et al.
· 2003
[cited by applicant]
US 6593081B1
· Griffiths et al.
· 2003
[cited by applicant]
US 6737056B1
· Presta
· 2004
[cited by applicant]
US 6989452B2
· Ng et al.
· 2006
[cited by applicant]
US 7087600B2
· Ng et al.
· 2006
[cited by applicant]
US 7129261B2
· Ng et al.
· 2006
[cited by applicant]
US 7317091B2
· Lazar et al.
· 2008
[cited by applicant]
US 7635757B2
· Freeman et al.
· 2009
[cited by applicant]
US 7943743B2
· Korman et al.
· 2011
[cited by applicant]
US 8101720B2
· Lazar et al.
· 2012
[cited by applicant]
US 8217149B2
· Irving et al.
· 2012
[cited by applicant]
US 8841418B2
· Karsunky et al.
· 2014
[cited by applicant]
US 9103832B2
· Takayanagi et al.
· 2015
[cited by applicant]
US 9334331B2
· Igawa et al.
· 2016
[cited by applicant]
US 9556270B2
· Takayanagi et al.
· 2017
[cited by applicant]
US 20040014194A1
· Beyer et al.
· 2004
[cited by applicant]
US 20090145493A1
· Lee
· 2009
[cited by applicant]
US 20100069614A1
· Houtzager et al.
· 2010
[cited by applicant]
US 20110007023A1
· Abrahamsson et al.
· 2011
[cited by applicant]
US 20110150892A1
· Thudium et al.
· 2011
[cited by applicant]
US 20140065142A1
· Roschke et al.
· 2014
[cited by applicant]
US 20190248893A1
· Schebye et al.
· 2019
[cited by applicant]
US 20210363242A1
· Schebye et al.
· 2021
[cited by applicant]
CN 102492038A
· 2012
[cited by applicant]
CN 103721255A
· 2014
[cited by applicant]
CN 104592388A
· 2015
[cited by applicant]
CN 103936853B
· 2016
[cited by applicant]
CN 106632675A
· 2017
[cited by applicant]
EP 0154316A2
· 1985
[cited by applicant]
EP 0338841A1
· 1989
[cited by applicant]
EP 0401384A1
· 1990
[cited by applicant]
EP 1176195A1
· 2002
[cited by applicant]
EP 2535355A2
· 2012
[cited by applicant]
JP 2006517581A
· 2006
[cited by applicant]
JP 2008278814A
· 2008
[cited by applicant]
KR 20160113272A
· 2016
[cited by applicant]
KR 20170035089A
· 2017
[cited by applicant]
WO WO8704462A1
· 1987
[cited by applicant]
WO WO8901036A1
· 1989
[cited by applicant]
WO WO9203918A1
· 1992
[cited by applicant]
WO WO9312227A1
· 1993
[cited by applicant]
WO WO9425585A1
· 1994
[cited by applicant]
WO WO9429351A2
· 1994
[cited by applicant]
WO WO9517886A1
· 1995
[cited by applicant]
WO WO9627603A1
· 1996
[cited by applicant]
WO WO9632478A1
· 1996
[cited by applicant]
WO WO9713852A1
· 1997
[cited by applicant]
WO WO9734631A1
· 1997
[cited by applicant]
WO WO9824884A1
· 1998
[cited by applicant]
WO WO9842752A1
· 1998
[cited by applicant]
WO WO9945962A1
· 1999
[cited by applicant]
WO WO9954342A1
· 1999
[cited by applicant]
WO WO0037504A2
· 2000
[cited by applicant]
WO WO0042072A2
· 2000
[cited by applicant]
WO WO0114424A2
· 2001
[cited by applicant]
WO WO0158957A2
· 2001
[cited by applicant]
WO WO0206919A2
· 2002
[cited by applicant]
WO WO0243478A2
· 2002
[cited by applicant]
WO WO02092780A2
· 2002
[cited by applicant]
WO WO02096910A1
· 2002
[cited by applicant]
WO WO03002722A2
· 2003
[cited by applicant]
WO WO03035835A2
· 2003
[cited by applicant]
WO WO03063792A2
· 2003
[cited by applicant]
WO WO03074679A2
· 2003
[cited by applicant]
WO WO03099196A2
· 2003
[cited by applicant]
WO WO2004016750A2
· 2004
[cited by applicant]
WO WO2004029207A2
· 2004
[cited by applicant]
WO WO2004035752A2
· 2004
[cited by applicant]
WO WO2004063351A2
· 2004
[cited by applicant]
WO WO2004074455A2
· 2004
[cited by applicant]
WO WO2004099249A2
· 2004
[cited by applicant]
WO WO2005027854A2
· 2005
[cited by applicant]
WO WO2005033144A2
· 2005
[cited by applicant]
WO WO2005040217A2
· 2005
[cited by applicant]
WO WO2005044853A2
· 2005
[cited by applicant]
WO WO2005070963A1
· 2005
[cited by applicant]
WO WO2005092925A2
· 2005
[cited by applicant]
WO WO2005097211A2
· 2005
[cited by applicant]
WO WO2006020114A2
· 2006
[cited by applicant]
WO WO2006029879A2
· 2006
[cited by applicant]
WO WO2006105021A2
· 2006
[cited by applicant]
WO WO2006121168A1
· 2006
[cited by applicant]
WO WO2006122150A1
· 2006
[cited by applicant]
WO WO2007005874A2
· 2007
[cited by applicant]
WO WO2007038658A2
· 2007
[cited by applicant]
WO WO2007051081A1
· 2007
[cited by applicant]
WO WO2007059404A2
· 2007
[cited by applicant]
WO WO2007075598A2
· 2007
[cited by applicant]
WO WO2008036642A2
· 2008
[cited by applicant]
WO WO2008036653A2
· 2008
[cited by applicant]
WO WO2008060617A2
· 2008
[cited by applicant]
WO WO2008083312A2
· 2008
[cited by applicant]
WO WO2008103693A2
· 2008
[cited by applicant]
WO WO2008132601A1
· 2008
[cited by applicant]
WO WO2009014708A2
· 2009
[cited by applicant]
WO WO2009015777A1
· 2009
[cited by applicant]
WO WO2009044273A2
· 2009
[cited by applicant]
WO WO2009052623A1
· 2009
[cited by applicant]
WO WO2009059278A1
· 2009
[cited by applicant]
WO WO2009073620A2
· 2009
[cited by applicant]
WO WO2009097394A2
· 2009
[cited by applicant]
WO WO2009114335A2
· 2009
[cited by applicant]
WO WO2009120899A2
· 2009
[cited by applicant]
WO WO2009120903A2
· 2009
[cited by applicant]
WO WO2009120905A2
· 2009
[cited by applicant]
WO WO2010019570A2
· 2010
[cited by applicant]
WO WO2010084999A1
· 2010
[cited by applicant]
WO WO2010117057A1
· 2010
[cited by applicant]
WO WO2011028683A1
· 2011
[cited by applicant]
WO WO2011056652A1
· 2011
[cited by applicant]
WO WO2011066389A1
· 2011
[cited by applicant]
WO WO2011070024A1
· 2011
[cited by applicant]
WO WO2011072204A1
· 2011
[cited by applicant]
WO WO2011097603A1
· 2011
[cited by applicant]
WO WO2011107553A1
· 2011
[cited by applicant]
WO WO2011109400A2
· 2011
[cited by applicant]
WO WO2011131407A1
· 2011
[cited by applicant]
WO WO2011140249A2
· 2011
[cited by applicant]
WO WO2011155607A1
· 2011
[cited by applicant]
WO WO2011159877A2
· 2011
[cited by applicant]
WO WO2011161699A2
· 2011
[cited by applicant]
WO WO2011163311A1
· 2011
[cited by applicant]
WO WO2011163314A1
· 2011
[cited by applicant]
WO WO2012032433A1
· 2012
[cited by applicant]
WO WO2012042237A1
· 2012
[cited by applicant]
WO WO2012145493A1
· 2012
[cited by applicant]
WO WO2012148873A2
· 2012
[cited by applicant]
WO WO2013006490A2
· 2013
[cited by applicant]
WO WO2013006727A1
· 2013
[cited by applicant]
WO WO2013079174A1
· 2013
[cited by applicant]
WO WO2013087699A1
· 2013
[cited by applicant]
WO WO2013119716A1
· 2013
[cited by applicant]
WO WO2013124324A1
· 2013
[cited by applicant]
WO WO2013124327A1
· 2013
[cited by applicant]
WO WO2013132044A1
· 2013
[cited by applicant]
WO WO2013169264A1
· 2013
[cited by applicant]
WO WO2013173223A1
· 2013
[cited by applicant]
WO WO2014008218A1
· 2014
[cited by applicant]
WO WO2014022332A1
· 2014
[cited by applicant]
WO WO2014036357A1
· 2014
[cited by applicant]
WO WO2015018735A2
· 2015
[cited by applicant]
WO WO2015031667A2
· 2015
[cited by applicant]
WO WO2015048312A1
· 2015
[cited by applicant]
WO WO2015069770A1
· 2015
[cited by applicant]
WO WO2015109931A1
· 2015
[cited by applicant]
WO WO2015117002A1
· 2015
[cited by applicant]
WO WO2015175340A1
· 2015
[cited by applicant]
WO WO2015184099A1
· 2015
[cited by applicant]
WO WO2015187835A2
· 2015
[cited by applicant]
WO WO2016007513A1
· 2016
[cited by applicant]
WO WO2016054638A1
· 2016
[cited by applicant]
WO WO2016057705A1
· 2016
[cited by applicant]
WO WO2016057841A1
· 2016
[cited by applicant]
WO WO2016057846A1
· 2016
[cited by applicant]
WO WO2016068802A1
· 2016
[cited by applicant]
WO WO2016068803A1
· 2016
[cited by applicant]
WO WO2016070051A2
· 2016
[cited by applicant]
WO WO2016071448A1
· 2016
[cited by applicant]
WO WO2016081746A2
· 2016
[cited by applicant]
WO WO2016111947A2
· 2016
[cited by applicant]
WO WO2016123285A1
· 2016
[cited by applicant]
WO WO2016141357A1
· 2016
[cited by applicant]
WO WO2016144803A2
· 2016
[cited by applicant]
WO WO2016161270A1
· 2016
[cited by applicant]
WO WO2016166139A1
· 2016
[cited by applicant]
WO WO2016168716A1
· 2016
[cited by applicant]
WO WO2016168771A2
· 2016
[cited by applicant]
WO WO2016171722A1
· 2016
[cited by applicant]
WO WO2016172417A2
· 2016
[cited by applicant]
WO WO2016179194A1
· 2016
[cited by applicant]
WO WO2016179472A2
· 2016
[cited by applicant]
WO WO2017019897A1
· 2017
[cited by applicant]
WO WO2017021526A1
· 2017
[cited by applicant]
WO WO2017031242A1
· 2017
[cited by applicant]
WO WO2017055399A1
· 2017
[cited by applicant]
WO WO2017055404A1
· 2017
[cited by applicant]
WO WO2017079112A1
· 2017
[cited by applicant]
WO WO2017079115A1
· 2017
[cited by applicant]
WO WO2017079116A2
· 2017
[cited by applicant]
WO WO2017178493A1
· 2017
[cited by applicant]
WO WO2017205721A1
· 2017
[cited by applicant]
WO WO2018013818A2
· 2018
[cited by applicant]
WO WO2018036561A1
· 2018
[cited by applicant]
WO WO2018039020A1
· 2018
[cited by applicant]
WO WO2018058123A1
· 2018
[cited by applicant]
WO WO2018085469A2
· 2018
[cited by applicant]
WO WO2018106529A1
· 2018
[cited by applicant]
WO WO2018106588A1
· 2018
[cited by applicant]
WO WO2018126233A1
· 2018
[cited by applicant]
WO WO2018185232A1
· 2019
[cited by applicant]
WO WO2018191074A1
· 2019
[cited by applicant]
WO WO2019099838A1
· 2020
[cited by applicant]
Anderson, A.C., “Tim-3: an Emerging Target in the Cancer Immunotherapy Landscape ,” Cancer Immunology Research 2(5):393-398, American Association for Cancer Research, United States (2014).
[cited by applicant]
Bird, R.E., et al., “Single-chain Antigen-binding Proteins,” Science 242(4877):423-426, Association for the Advancement of Science, United States (Oct. 1988).
[cited by applicant]
Brennan, M., et al., “Preparation of Bispecific Antibodies by Chemical Recombination of Monoclonal Immunoglobulin G1 Fragments,” Science 229(4708):81-83, American Association for the Advancement of Science, United State…
[cited by applicant]
Brummell, D.A., et al., “Probing the Combining Site of an Anti-Carbohydrate Antibody by Saturation-Mutagenesis: Role of the Heavy-Chain CDR3 Residues,” Biochemistry 32(4):1180-1187, American Chemical Society, United Sta…
[cited by applicant]
Burks, E.A., et al., “In vitro Scanning Saturation Mutagenesis of an Antibody Binding Pocket,” Proceedings of the National Academy of Sciences USA 94(2):412-417, Plenum Publishing Corporation, United States (1997).
[cited by applicant]
Cox, J.P., et al., “A Directory of Human Germ-line V kappa Segments Reveals a Strong Bias in their Usage,” European Journal of Immunology 24(4):827-836, Verlag Chemie GmbH, Germany (Apr. 1994).
[cited by applicant]
Cunningham, B.C. and Wells, J.A., “High-resolution Epitope Mapping of hGH-receptor Interactions by Alanine-scanning Mutagenesis,” Science 244(4908):1081-1085, American Association for the Advancement of Science, United …
[cited by applicant]
Dall Acqua, W.F., et al., “Increasing the Affinity of a Human IgG1 for the Neonatal Fc Receptor: Biological Consequences,” The Journal of Immunology 169(9):5171-5180, American Association of Immunologists, United States…
[cited by applicant]
Dall'Acqua, W.F., et al., “Properties of Human IgG1s Engineered for Enhanced Binding to the Neonatal Fc Receptor (FcRn),” The Journal of Biological Chemistry 281(33):23514-23524, American Society for Biochemistry and Mo…
[cited by applicant]
Dranoff, G., et al., “Vaccination With Irradiated Tumor Cells Engineered to Secrete Murine Granulocyte-macrophage Colony-stimulating Factor Stimulates Potent, Specific, and Long-lasting Anti-tumor Immunity,” Proceedings…
[cited by applicant]
Fourcade, J., et al., “Upregulation of Tim-3 and PDd-1 Expression Is Associated With Tumor Antigen-specific CD8+ T Cell Dysfunction in Melanoma Patients,” The Journal of Experimental Medicine 207(10):2175-2186, Rockefel…
[cited by applicant]
Gala, F.A. and Morrison, S.L., “V Region Carbohydrate and Antibody Expression,” The Journal of Immunology 172(9):5489-5494, Williams & Wilkins, United States (2004).
[cited by applicant]
GenBank, “HAVCR2 protein [
[cited by applicant]
GenBank, “Hepatitis A Virus Cellular Receptor 2 Precursor [
[cited by applicant]
GenBank, “
[cited by applicant]
GenBank, “
[cited by applicant]
Glennie, M.J., et al., “Preparation and Performance of Bispecific F(Ab' Gamma)2 Antibody Containing Thioether-linked Fab' Gamma Fragments,” Journal of Immunology 139(7):2367-2375, American Association of Immunologists, …
[cited by applicant]
Han, G., et al., “Tim-3: an Activation Marker and Activation Limiter of Innate Immune Cells,” Frontiers in Immunology 4:449, Frontiers Research, Switzerland (2013).
[cited by applicant]
He, Y-F., et al., “Blocking Programmed Death-1 Ligand-PD-1 Interactions by Local Gene Therapy Results in Enhancement of Antitumor Effect of Secondary Lymphoid Tissue Chemokine,” The Journal of Immunology 173(8):4919-492…
[cited by applicant]
Hinton, P.R., et al., “An Engineered Human IgG1 Antibody with Longer Serum Half-Life,” Journal of Immunology 176(1):346-356, American Association of Immunologists, United States (2006).
[cited by applicant]
Hinton, P.R., et al., “Engineered Human IgG Antibodies With Longer Serum Half-lives in Primates,” The Journal of Biological Chemistry 279(8):6213-6216, American Society for Biochemistry and Molecular Biology, United Sta…
[cited by applicant]
Holliger, P., et al., “Diabodies: Small Bivalent and Bispecific Antibody Fragments,” Proceedings of the National Academy of Sciences USA 90(14):6444-6448, National Academy of Sciences, United States (Jul. 1993).
[cited by applicant]
Hurwitz, A.A., et al., “CTLA-4 Blockade Synergizes With Tumor-derived Granulocyte-macrophage Colony-stimulating Factor for Treatment of an Experimental Mammary Carcinoma,” Proceedings of the National Academy of Sciences…
[cited by applicant]
Huston, J.S., et al., “Protein Engineering of Antibody Binding Sites: Recovery of Specific Activity in an Anti-digoxin Single-chain Fv Analogue Produced in
[cited by applicant]
Hutloff, A., et al., “ICOS is an Inducible T-cell Co-stimulator Structurally and Functionally Related to CD28,” Nature 397(6716):263-266, Nature Publishing Group, England (Jan. 1999).
[cited by applicant]
Hyer, M.L., et al., “Synthetic Triterpenoids Cooperate With Tumor Necrosis Factor-related Apoptosis-inducing Ligand to Induce Apoptosis of Breast Cancer Cells,” Cancer Research 65(11):4799-4808, American Association for…
[cited by applicant]
Kabat, E.A., et al., “Sequences of Proteins of Immunological Interest,” 5th Edition, U.S. Department of Public Health and Human Services, Public Health Service, National Institutes of Health, Bethesda (1991).
[cited by applicant]
Keinanen, K. and Laukkanen, M.L., “Biosynthetic Lipid-tagging of Antibodies,” FEBS Letters 346(1):123-126, John Wiley & Sons Ltd, England (1994).
[cited by applicant]
Kobayashi, H., et al., “Tryptophan H33 Plays an Important Role in Pyrimidine (6-4) Pyrimidone Photoproduct Binding by a High-Affinity Antibody,” Protein Engineering Design and Selection 12(10):879-884, Oxford University…
[cited by applicant]
Kostelny, S.A., et al., “Formation of a Bispecific Antibody by the Use of Leucine Zippers,” The Journal of Immunology 148(5):1547-1553, American Association of Immunologists, United States (Mar. 1992).
[cited by applicant]
Krishnamurthy, R. and Manning, M.C., “The Stability Factor: Importance in Formulation Development,” Current Pharmaceutical Biotechnology 3(4):361-371, Bentham Science Publishers, Netherlands (2002).
[cited by applicant]
Liu, M.A., et al., “Heteroantibody Duplexes Target Cells for Lysis by Cytotoxic T Lymphocytes,” Proceedings of the National Academy of Sciences of the United States of America 82(24):8648-8652, National Academy of Scien…
[cited by applicant]
Lonberg, N. and Huszar, D., “Human Antibodies from Transgenic Mice,” International Reviews of Immunology 13(1):65-93, Informa Healthcare, England (1995).
[cited by applicant]
Lonberg, N., et al., “Antigen-specific Human Antibodies from Mice Comprising Four Distinct Genetic Modifications,” Nature 368(6474):856-859, Nature Publishing Group, United States (Apr. 1994).
[cited by applicant]
McCafferty, J., et al., “Phage Antibodies: Filamentous Phage Displaying Antibody Variable Domains,” Nature 348(6301):552-554, Nature Publishing Group, London (Dec. 1990).
[cited by applicant]
Melero, I., et al., “Monoclonal Antibodies Against the 4-1BB T-cell Activation Molecule Eradicate Established Tumors,” Nature Medicine 3(6):682-685, Nature Publishing Company, United States (1997).
[cited by applicant]
Mimura, Y., et al., “The Influence of Glycosylation on the Thermal Stability and Effector Function Expression of Human IgG1-Fc: Properties of a Series of Truncated Glycoforms,” Molecular Immunology 37(12-13):697-706, Pe…
[cited by applicant]
Mokyr, M.B., et al., “Realization of the Therapeutic Potential of CTLA-4 Blockade in Low-dose Chemotherapy-treated Tumor-bearing Mice,” Cancer Research 58(23):5301-5304, American Association for Cancer Research, United …
[cited by applicant]
Morrison, S.L., “Transfectomas Provide Novel Chimeric Antibodies,” Science 229(4719):1202-1207, Association for the Advancement of Science, United States (Sep. 1985).
[cited by applicant]
Murray, A., et al., “Epitope Affinity Chromatography and Biophysical Studies of Monoclonal Antibodies and Recombinant Antibody Fragments,” Journal of Chromatographic Science 40(6):343-349, Oxford University Press, Unite…
[cited by applicant]
Nakayama, M., et al., “Tim-3 Mediates Phagocytosis of Apoptotic Cells and Cross-presentation,” Blood 113(16):3821-3830, American Society of Hematology, United States (2009).
[cited by applicant]
Ngiow, S.F., et al., “Anti-TIM3 Antibody Promotes T Cell IFN-γ-mediated Antitumor Immunity and Suppresses Established Tumors,” Cancer Research 71(10):3540-3451, American Association for Cancer Research, United States (2…
[cited by applicant]
Parekh, R.B., et al., “Association of Rheumatoid Arthritis and Primary Osteoarthritis with Changes in the Glycosylation Pattern of Total Serum IgG,” Nature 316(6027):452-457, Nature Publishing Group, England (1985).
[cited by applicant]
Zhou, Q., et al., “Coexpression of Tim-3 and PD-1 Identifies a CD8+ T-Cell Exhaustion Phenotype in Mice With Disseminated Acute Myelogenous Leukemia,” Blood 117(17):4501-4510, American Society of Hematology, United Stat…
[cited by applicant]
Pei-Show Juo., The Concise Dictionary of Biomedicine and Molecular Biology, 2nd Edition, CRC Press, United States (2002).
[cited by applicant]
Poljak, R.J., “Production and Structure of Diabodies,” Structure 2(12):1121-1123, Cell Press, United States (1994).
[cited by applicant]
Queen, C., et al., “A Humanized Antibody that Binds to the Interleukin 2 Receptor,” Proceedings of the National Academy of Sciences USA 86(24):10029-10033, National Academy of Sciences, United States (Dec. 1989).
[cited by applicant]
Riechmann, L., et al., “Reshaping Human Antibodies for Therapy,” Nature 332(6162):323-327, Nature Publishing Group, United States (Mar. 1988).
[cited by applicant]
Riedl, S., et al., “In Search of a Novel Target—Phosphatidylserine Exposed by Non-apoptotic Tumor Cells and Metastases of Malignancies With Poor Treatment Efficacy,” Biochimica Et Biophysica Acta 1808(11):2638-2645, Els…
[cited by applicant]
Rosenberg, S.A., “A New Era for Cancer Immunotherapy Based on the Genes That Encode Cancer Antigens,” Immunity 10(3):281-287, Cell Press, United States (1999).
[cited by applicant]
Sarmay, G., et al., “Mapping and Comparison of the Interaction Sites on the Fc Region of IgG Responsible for Triggering Antibody Dependent Cellular Cytotoxicity (ADCC) Through Different Types of Human Fc Gamma Receptor,…
[cited by applicant]
Senter, P.D., “Potent Antibody Drug Conjugates for Cancer Therapy,” Current Opinion in Chemical Biology 13(3):235-244, Elsevier, England (2009).
[cited by applicant]
Shields, R.L., et al., “High Resolution Mapping of the Binding Site on Human IgG1 for Fc gamma RI, Fc gamma RII, Fc gamma RIII, and FcRn and Design of IgG1 Variants with Improved Binding to the Fc gamma R,” The Journal …
[cited by applicant]
Shields, R.L., et al., “Lack of Fucose on Human IgG1 N-linked Oligosaccharide Improves Binding to Human Fcgamma RIII and Antibody-Dependent Cellular Toxicity,” The Journal of Biological Chemistry 277(30):26733-26740, Am…
[cited by applicant]
Songsivilai, S. and Lachmann, P.J., “Bispecific Antibody: A Tool for Diagnosis and Treatment of Disease,” Clinical and Experimental Immunology 79(3):315-321, Blackwell Scientific Publications, England (1990).
[cited by applicant]
Spiro, R.G., “Protein Glycosylation: Nature, Distribution, Enzymatic Formation, and Disease Implications of Glycopeptide Bonds,” Glycobiology 12(4):43R-56R, IRL Press at Oxford University Press, England (2002).
[cited by applicant]
Stavenhagen, J.B., et al., “Fc Optimization of Therapeutic Antibodies Enhances Their Ability to Kill Tumor Cells in Vitro and Controls Tumor Expansion in Vivo via Low-affinity Activating Fcgamma Receptors,” Cancer Resea…
[cited by applicant]
Strohl, W.R., “Optimization of Fc-mediated Effector Functions of Monoclonal Antibodies,” Current Opinion in Biotechnology 20(6):685-691, Elsevier, England (2009).
[cited by applicant]
Taylor, L.D., et al., “A Transgenic Mouse That Expresses a Diversity of Human Sequence Heavy and Light Chain Immunoglobulins,” Nucleic Acids Research 20(23):6287-6295, Oxford University Press, England (1992).
[cited by applicant]
Tomizuka, K., et al., “Double Trans-chromosomic Mice: Maintenance of Two Individual Human Chromosome Fragments Containing Ig Heavy and kappa loci and Expression of Fully Human Antibodies,” Proceedings of the National Ac…
[cited by applicant]
Tomlinson, I.M., et al., “The Repertoire of Human Germline VH Sequences Reveals about Fifty Groups of VH Segments with Different Hypervariable Loops,” Journal of Molecular Biology 227(3):776-798, Elsevier, Netherlands (…
[cited by applicant]
Tuaillon, N., et al., “Biased Utilization of DHQ52 and JH4 Gene Segments in a Human Ig Transgenic Minilocus Is Independent of Antigenic Selection,” The Journal of Immunology 152(6):2912-2920, Williams & Wilkins, United …
[cited by applicant]
Tuaillon, N., et al., “Human Immunoglobulin Heavy-chain Minilocus Recombination in Transgenic Mice: Gene-segment Use in Mu and Gamma Transcripts,” Proceedings of the National Academy of Sciences of the United States of …
[cited by applicant]
Umana, P., et al., “Engineered Glycoforms of an Antineuroblastoma IgG1 with Optimized Antibody-Dependent Cellular Cytotoxic Activity,” Nature Biotechnology 17(2):176-180, Nature America Publishing, United States (1999).
[cited by applicant]
Urlaub, G. and Chasin, L.A., “Isolation of Chinese Hamster Cell Mutants Deficient in Dihydrofolate Reductase Activity,” Proceedings of the National Academy of Sciences USA 77(7):4216-4220, National Academy of Sciences, …
[cited by applicant]
Wallick, S.C., et al., “Glycosylation of a Vh Residue of a Monoclonal Antibody Against Alpha (1-6) Dextran Increases Its Affinity for Antigen,” The Journal of Experimental Medicine 168(3):1099-1109, Rockefeller Universi…
[cited by applicant]
Ward, E.S., et al., “Binding Activities of a Repertoire of Single Immunoglobulin Variable Domains Secreted from
[cited by applicant]
Weinberg, A.D., et al., “Engagement of the OX-40 Receptor in Vivo Enhances Antitumor Immunity,” Journal of Immunology 164(4):2160-2169, American Association of Immunologists, United States (2000).
[cited by applicant]
Yeung, Y.A., et al., “Engineering Human IgG1 Affinity to Human Neonatal Fc Receptor: Impact of Affinity Improvement on Pharmacokinetics in Primates,” Journal of Immunology 182(12):7663-7671, American Association of Immu…
[cited by applicant]
Freeman, G., et al., “TIM genes: a family of cell surface phosphatidlyserine receptors that regulate innate and adaptive immunity,” Immunol Rev. 235(1):172-189, Elsevier, Netherlands (2010).
[cited by applicant]
Dekruyff, R.H., et al., “T Cell/Transmembrne, Ig, and Mucin-3 Allelic variants Differentially Recognize Phosphatidylserine and mdiate Phagocytosis of Apoptotic cells,” Journal of Immunology 184:1918-1930, American Assoc…
[cited by applicant]
Jefferis,R., et al., “Human Immunoglobulin allotypes,” MAbs 1(4):332-338, Taylor & Francis, United Kingdom (2009).
[cited by applicant]
Protein Data Bank, “Human T-cell immunoglobulin and mucin domain protein 3 (hTIM-3),” 5F71, accessed at http://www.rcsb.org/pdb/explore/explore.do?pdbId=5F71 , accessed on Jul. 27, 2017, 2 pages.
[cited by applicant]
Protein Data Bank, “Structure of Tim-3 in complex with phosphatidylserine,” 3KAA, accessed at http://www.rcsb.org/pdb/explore/explore.do?structureId=3kaa, accessed on Jul. 27, 2017, 2 pages.
[cited by applicant]
Mcintire, J.J., et al., “Identification of Tapr (An Airway Hyperreactivity Regulatory Locus) and the Linked Tim Gene Family,” Nature Immunology 2(12):1109-1116, Nature America Inc, United States (Dec. 2001).
[cited by applicant]
Monney, L., et al., “Identification and Characterization of Novel Cell Surface Molecules Expressed on TH1 cells,” Scandinavian Journal of Immunology 54:35, (2001).
[cited by applicant]
Monney, L., et al., “Th1-Specific Cell Surface Protein Tim-3 Regulates Macrophage Activation and Severity of an Autoimmune Disease,” Nature 415(6871):536-541, Nature Publishing Group, England (Jan. 2002).
[cited by applicant]
Kikushige, Y., et al., “TIM-3 as a novel therapeutic target for eradicating acute myelogenous leukemia stem cells,”
[cited by applicant]
Ferris, R.L., et al., “Too Much of a Good thing? Tim-3 and TCR Signaling in T Cell Exhaustion,”
[cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2017/041946, European Patent Office, Iceland, mailed on Jan. 3, 2018, 22 pages.
[cited by applicant]
Kreig, C., et al., “Functional analysis of B and T lymphocyte attenuator engagement on CD4+ and CD8+ T cells,” J Immunol 175(10):6420-7 (Nov. 2005).
[cited by applicant]
Justice et al., “Using the mouse to model human disease: increasing validity and reproducibility,” Disease, Models & Mechanisms 9: 101-103 (Feb. 2016).
[cited by applicant]
Tokuriki et al., “Stability effects of mutations and protein evolvability,”
[cited by applicant]
Fenton et al., “Rheostat positions: A new classification of protein positions relevant to pharmacogenomics,”
[cited by applicant]
De Pascalis et al., “Grafting of ‘abbreviated’ complementarity-determining regions containing specificity-determining residues essential for ligant contact to engineer a less immunogenic humanized monoclonal antibody,”
[cited by applicant]
Bose and Sinha, “Problems in using statistical analysis of replacement and silent mutations in antibody genes for determining antigen-driven affinity selection,”
[cited by applicant]
Vajdos et al., “Comprehensive functional maps of the antigen-binding site of an anti-ErobB2 antibody obtained with shotgun scanning mutagenesis,”
[cited by applicant]
Guo et al., “Protein tolerance to random amino acid change,”
[cited by applicant]
Ha et al., “Animal models of melanoma,”
[cited by applicant]
Non-final Office Action mailed Dec. 19, 2022, in U.S. Appl. No. 16/316,991, filed Jan. 10, 2019 (22 pages).
[cited by applicant]
McKinney and Holmen, “Animal models of melanoma: a somatic cell gene delivery mouse model allows rapid evaluation of genes implicated in human melanoma,”
[cited by applicant]
Final Office Action mailed Jul. 5, 2023, in U.S. Appl. No. 16/316,991, filed Jan. 10, 2019 (13 pages).
[cited by applicant]
Non-final Office Action mailed Feb. 14, 2022, in U.S. Appl. No. 16/697,653, filed Nov. 27, 2019 (7 pages).
[cited by applicant]
Non-final Office Action mailed Jan. 18, 2019, in U.S. Appl. No. 16/017,489, filed Jun. 25, 2018 (8 pages).
[cited by applicant]
Final Office Action mailed May 13, 2019, in U.S. Appl. No. 16/017,489, filed Jun. 25, 2018 (7 pages).
[cited by applicant]
Non-final Office Action mailed Nov. 6, 2017, in U.S. Appl. No. 15/649,380, filed Jul. 13, 2017 (7 pages).
[cited by applicant]
Gros, A., et al., “PD-1 identifies the patient-specific CD8+ tumor-reactive repertoire infiltrating human tumors,”
[cited by applicant]
Baitsch, L., et al., “Exhaustion of tumor-specific CD8+ T cells in metastases from melanoma patients,”
[cited by applicant]
Morris, G.E., et al., “Epitope Mapping of Protein Antigens by Competition ELISA,” The Protein Protocols Handbook, pp. 595-600, Humana Press, United States (1996).
[cited by applicant]
Non-final Office Action dated Aug. 7, 2024, in U.S. Appl. No. 18/481,884, filed Oct. 5, 2023, 14 pages.
[cited by applicant]