IP Library › Granted Patent US 12,735,507
Granted Patent B2
US 12,735,507 · App. 17/291,986 · Granted Sep 15, 2026

Antibodies recognizing tau

Inventors: Tarlochan S. Nijjar (Orinda, CA); Robin Barbour (Walnut Creek, CA); Philip James Dolan, III (Foster City, CA); Yue Liu (Foster City, CA); Svetlana Alexander (Sunnyvale, CA); Mark E. Renz (Millbrae, CA)
Assignee: Prothena Biosciences Limited
C07K16/461A61K47/6843C07K16/18C07K2317/24C07K2317/52C07K2317/55C07K2317/622C07K2317/92
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Quick Facts
Patent No.
US 12,735,507
App. No.
17/291,986
Granted
Sep 15, 2026
Kind
B2
Abstract

The invention provides antibodies that specifically bind tau. The antibodies inhibit or delay tau-associated pathologies and associated symptomatic deterioration.

Claims (36)

1 . A humanized antibody or antigen-binding antibody fragment that binds specifically to human tau, comprising:

(a) a humanized mature heavy chain variable region comprising CDRs H1, H2, and H3 comprising SEQ ID NOs: 8, 9, and a sequence of LDF, respectively, and a humanized mature light chain variable region comprising CDRs L1, L2, and L3 comprising SEQ ID NOs: 12, 13, and 14, respectively;

(b) a humanized mature heavy chain variable region comprising CDRs H1, H2, and H3 comprising SEQ ID NOs: 8, 9, and a sequence of LDF, respectively, and a humanized mature light chain variable region comprising CDRs L1, L2, and L3 comprising SEQ ID NOs: 89, 13, and 14, respectively;

(c) a humanized mature heavy chain variable region comprising CDRs H1, H2, and H3 comprising SEQ ID NOs: 8, 87, and a sequence of LDF, respectively, and a humanized mature light chain variable region comprising CDRs L1, L2, and L3 comprising SEQ ID NOs: 12, 13, and 14, respectively;

(d) a humanized mature heavy chain variable region comprising CDRs H1, H2, and H3 comprising SEQ ID NOs: 8, 87, and a sequence of LDF, respectively, and a humanized mature light chain variable region comprising CDRs L1, L2, and L3 comprising SEQ ID NOs: 89, 13, and 14, respectively;

(e) a humanized mature heavy chain variable region comprising CDRs H1, H2, and H3 comprising SEQ ID NOs: 86, 87, and a sequence of LDF, respectively, and a humanized mature light chain variable region comprising CDRs L1, L2, and L3 comprising SEQ ID NOs: 12, 13, and 14, respectively;

(f) a humanized mature heavy chain variable region comprising CDRs H1, H2, and H3 comprising SEQ ID NOs: 86, 87, and a sequence of LDF, respectively, and a humanized mature light chain variable region comprising CDRs L1, L2, and L3 comprising SEQ ID NOs: 89, 13, and 14, respectively;

(g) a humanized mature heavy chain variable region comprising CDRs H1, H2, and H3 comprising SEQ ID NOs: 86, 88, and a sequence of LDF, respectively, and a humanized mature light chain variable region comprising CDRs L1, L2, and L3 comprising SEQ ID NOs: 12, 13, and 14, respectively;

(h) a humanized mature heavy chain variable region comprising CDRs H1, H2, and H3 comprising SEQ ID NOs: 86, 88, and a sequence of LDF, respectively, and a humanized mature light chain variable region comprising CDRs L1, L2, and L3 comprising SEQ ID NOs: 89, 13, and 14, respectively;

(i) a humanized mature heavy chain variable region comprising CDRs H1, H2, and H3 comprising SEQ ID NOs: 86, 92, and a sequence of LDF, respectively, and a humanized mature light chain variable region comprising CDRs L1, L2, and L3 comprising SEQ ID NOs: 12, 13, and 14, respectively; or

(j) a humanized mature heavy chain variable region comprising CDRs H1, H2, and H3 comprising SEQ ID NOs: 86, 92, and a sequence of LDF, respectively, and a humanized mature light chain variable region comprising CDRs L1, L2, and L3 comprising SEQ ID NOs: 89, 13, and 14, respectively;

wherein Kabat positions L7, L10, L15, L17, L37, L45, L83, L86, L100, and L106 are occupied by S, S, L, E, Q, R, V, Y, Q, and I, respectively.

2 . The humanized antibody or antigen-binding antibody A fragment of claim 1 , provided Kabat positions H1, H5, H11, H20, H23, H38, H42, H43, H66, H75, H76, H81, H91, H93, H94, H108, and H109 are occupied by E, V, V, I, K, R, G, K, R, T, D, E, F, S, T, L, and V, respectively.

3 . The humanized antibody or antigen-binding antibody fragment of claim 1 , that is a humanized antigen-binding antibody fragment.

4 . The humanized antibody or antigen-binding antibody fragment of claim 3 , wherein the humanized antigen-binding antibody fragment is a single-chain antibody, a Fab, or a Fab′ 2 fragment.

5 . The humanized antibody or antigen-binding antibody fragment of claim 1 , wherein the humanized antibody has a human IgG1 isotype.

6 . The humanized antibody or antigen-binding antibody fragment of claim 1 ,

wherein the humanized mature light chain variable region is fused to a light chain constant region and the humanized mature heavy chain variable region is fused to a heavy chain constant region.

7 . The humanized antibody or antigen-binding antibody fragment of claim 6 , wherein the heavy chain constant region is a mutant form of a natural human heavy chain constant region which has reduced binding to a Fcγ receptor relative to the natural human heavy chain constant region.

8 . The humanized antibody or antigen-binding antibody fragment of claim 6 , wherein the humanized mature heavy chain variable region is fused to a heavy chain constant region having the sequence of SEQ ID NO: 103 with or without the C-terminal lysine and/or the humanized mature light chain variable region is fused to a light chain constant region having the sequence of SEQ ID NO: 104.

9 . The humanized antibody or antigen-binding antibody fragment of claim 1 , wherein the humanized antibody has a human IgG2 or a human IgG4 isotype.

10 . A pharmaceutical composition comprising the humanized antibody or antigen-binding antibody fragment of claim 1 and a pharmaceutically-acceptable carrier.

11 . The humanized antibody or antigen-binding antibody fragment of claim 1 , wherein:

the humanized mature heavy chain variable region comprises SEQ ID NO: 77 and the humanized mature light chain variable region comprises SEQ ID NO: 85;

the humanized mature heavy chain variable region comprises SEQ ID NO: 78 and the humanized mature light chain variable region comprises SEQ ID NO: 85;

the humanized mature heavy chain variable region comprises SEQ ID NO: 79 and the humanized mature light chain variable region comprises SEQ ID NO: 85;

the humanized mature heavy chain variable region comprises SEQ ID NO: 80 and the humanized mature light chain variable region comprises SEQ ID NO: 85;

the humanized mature heavy chain variable region comprises SEQ ID NO: 90 and the humanized mature light chain variable region comprises SEQ ID NO: 85;

or

the humanized mature heavy chain variable region comprises SEQ ID NO: 91 and the humanized mature light chain variable region comprises SEQ ID NO: 85.

12 . The humanized antibody or antigen-binding antibody fragment of claim 11 , wherein the humanized mature heavy chain variable region comprises SEQ ID NO: 77 and the humanized mature light chain variable region comprises SEQ ID NO: 85.

13 . The humanized antibody or antigen-binding antibody fragment of claim 11 , wherein the humanized mature heavy chain variable region comprises SEQ ID NO: 78 and the humanized mature light chain variable region comprises SEQ ID NO: 85.

14 . The humanized antibody or antigen-binding antibody fragment of claim 11 , wherein the humanized mature heavy chain variable region comprises SEQ ID NO: 79 and the humanized mature light chain variable region comprises SEQ ID NO: 85.

15 . The humanized antibody or antigen-binding antibody fragment of claim 11 , wherein the humanized mature heavy chain variable region comprises SEQ ID NO: 80 and the humanized mature light chain variable region comprises SEQ ID NO: 85.

16 . The humanized antibody or antigen-binding antibody fragment of claim 11 , wherein the humanized mature heavy chain variable region comprises SEQ ID NO: 90 and the humanized mature light chain variable region comprises SEQ ID NO: 85.

17 . The humanized antibody or antigen-binding antibody fragment of claim 11 , wherein the humanized mature heavy chain variable region comprises SEQ ID NO: 91 and the humanized mature light chain variable region comprises SEQ ID NO: 85.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 11, 2021
From: NIJJAR, TARLOCHAN S.; BARBOUR, ROBIN; DOLAN, PHILIP JAMES, III; LIU, YUE; ALEXANDER, SVETLANA; RENZ, MARK E.
To: PROTHENA BIOSCIENCES INC
Reel/Frame 057145/0629 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 11, 2021
From: PROTHENA BIOSCIENCES INC
To: PROTHENA BIOSCIENCES LIMITED
Reel/Frame 057145/0858 →
Priority Claims (1)
WO PCT/US2018/059895 · Nov 8, 2018 · international
Continuity (2)
Provisional Application 62758421 · Nov 9, 2018
Related Publication 20220153821A1 · May 19, 2022
References Cited (355)
US 4634664A · Oestberg · 1987 [cited by applicant]
US 4634666A · Engleman et al. · 1987 [cited by applicant]
US 5057540A · Kensil et al. · 1991 [cited by applicant]
US 5194594A · Khawli et al. · 1993 [cited by applicant]
US 5208036A · Eppstein et al. · 1993 [cited by applicant]
US 5225539A · Winter · 1993 [cited by applicant]
US 5264618A · Felgner et al. · 1993 [cited by applicant]
US 5279833A · Rose · 1994 [cited by applicant]
US 5283185A · Epand et al. · 1994 [cited by applicant]
US 5304489A · Rosen · 1994 [cited by applicant]
US 5530101A · Queen et al. · 1996 [cited by applicant]
US 5545806A · Lonberg et al. · 1996 [cited by applicant]
US 5565332A · Hoogenboom et al. · 1996 [cited by applicant]
US 5569825A · Lonberg 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 5643576A · Johnston et al. · 1997 [cited by applicant]
US 5661016A · Lonberg et al. · 1997 [cited by applicant]
US 5733743A · Johnson et al. · 1998 [cited by applicant]
US 5736142A · Sette et al. · 1998 [cited by applicant]
US 5741957A · Deboer et al. · 1998 [cited by applicant]
US 5770429A · Lonberg et al. · 1998 [cited by applicant]
US 5786464A · Seed et al. · 1998 [cited by applicant]
US 5789650A · Lonberg et al. · 1998 [cited by applicant]
US 5814318A · Lonberg et al. · 1998 [cited by applicant]
US 5834597A · Tso et al. · 1998 [cited by applicant]
US 5837242A · Holliger et al. · 1998 [cited by applicant]
US 5849992A · Meade et al. · 1998 [cited by applicant]
US 5858657A · Winter et al. · 1999 [cited by applicant]
US 5859205A · Adair et al. · 1999 [cited by applicant]
US 5871907A · Winter et al. · 1999 [cited by applicant]
US 5874299A · Lonberg et al. · 1999 [cited by applicant]
US 5877218A · Herzig et al. · 1999 [cited by applicant]
US 5877397A · Lonberg et al. · 1999 [cited by applicant]
US 5888809A · Allison et al. · 1999 [cited by applicant]
US 6063598A · Enenkel et al. · 2000 [cited by applicant]
US 6114148A · Seed et al. · 2000 [cited by applicant]
US 6407213B1 · Carter et al. · 2002 [cited by applicant]
US 6624821B1 · Shin et al. · 2003 [cited by applicant]
US 6881557B2 · Foote · 2005 [cited by applicant]
US 7442516B2 · Ohno et al. · 2008 [cited by applicant]
US 7569339B2 · Kaufmann et al. · 2009 [cited by applicant]
US 8012936B2 · Sigurdsson et al. · 2011 [cited by applicant]
US 8455622B2 · McDonagh et al. · 2013 [cited by applicant]
US 8778343B2 · Kayed · 2014 [cited by applicant]
US 8926974B2 · Griswold-Prenner et al. · 2015 [cited by applicant]
US 8987419B2 · Barghorn et al. · 2015 [cited by applicant]
US 9051367B2 · Griswold-Prenner et al. · 2015 [cited by applicant]
US 9321841B2 · Jones et al. · 2016 [cited by applicant]
US 9605054B2 · Brady et al. · 2017 [cited by applicant]
US 10196439B2 · Pedersen et al. · 2019 [cited by applicant]
US 10253100B2 · Igawa et al. · 2019 [cited by applicant]
US 10301379B2 · Wadia et al. · 2019 [cited by applicant]
US 10501531B2 · Seubert et al. · 2019 [cited by applicant]
US 10711058B2 · Adolfsson et al. · 2020 [cited by applicant]
US 10752679B2 · Seubert et al. · 2020 [cited by applicant]
US 10766953B2 · Mercken et al. · 2020 [cited by applicant]
US 10829547B2 · Roberts et al. · 2020 [cited by applicant]
US 10836817B2 · Adolfsson et al. · 2020 [cited by applicant]
US 10889638B2 · Barbour et al. · 2021 [cited by applicant]
US 10906964B2 · Barbour et al. · 2021 [cited by applicant]
US 10961302B2 · Barbour et al. · 2021 [cited by applicant]
US 20050009150A1 · Basi et al. · 2005 [cited by applicant]
US 20050114912A1 · Botas et al. · 2005 [cited by applicant]
US 20050132424A1 · Lowe et al. · 2005 [cited by applicant]
US 20070042359A1 · Throsby et al. · 2007 [cited by applicant]
US 20080050383A1 · Sigurdsson et al. · 2008 [cited by applicant]
US 20080076145A1 · Cummings et al. · 2008 [cited by applicant]
US 20090028851A1 · Stuhmer et al. · 2009 [cited by applicant]
US 20100022026A1 · Rump et al. · 2010 [cited by applicant]
US 20100216703A1 · Akassoglou et al. · 2010 [cited by applicant]
US 20100267927A1 · Garrett et al. · 2010 [cited by applicant]
US 20100316564A1 · Sigurdsson · 2010 [cited by applicant]
US 20110053264A1 · Kashmiri et al. · 2011 [cited by applicant]
US 20110206702A1 · Polakis et al. · 2011 [cited by applicant]
US 20120023911A1 · Liu et al. · 2012 [cited by applicant]
US 20120100152A1 · Roberts et al. · 2012 [cited by applicant]
US 20120142602A1 · Brady et al. · 2012 [cited by applicant]
US 20120149880A1 · Cheung et al. · 2012 [cited by applicant]
US 20120204275A1 · Schenk et al. · 2012 [cited by applicant]
US 20120288507A1 · Qian et al. · 2012 [cited by applicant]
US 20120301473A1 · Binder et al. · 2012 [cited by applicant]
US 20120308480A1 · Smith et al. · 2012 [cited by applicant]
US 20130189289A1 · Inoue et al. · 2013 [cited by applicant]
US 20130209453A1 · Black et al. · 2013 [cited by applicant]
US 20130295021A1 · Chen et al. · 2013 [cited by applicant]
US 20140056901A1 · Agadjanyan et al. · 2014 [cited by applicant]
US 20140086921A1 · Griswold-Prenner et al. · 2014 [cited by applicant]
US 20140171373A1 · Ashe et al. · 2014 [cited by applicant]
US 20140294731A1 · Pfeifer et al. · 2014 [cited by applicant]
US 20140294839A1 · Kuret et al. · 2014 [cited by applicant]
US 20150050215A1 · Novak et al. · 2015 [cited by applicant]
US 20150050270A1 · Sanofi · 2015 [cited by applicant]
US 20150056721A1 · Siman · 2015 [cited by applicant]
US 20150166661A1 · Chen et al. · 2015 [cited by applicant]
US 20150175682A1 · Pfeifer et al. · 2015 [cited by applicant]
US 20150196663A1 · Shusta et al. · 2015 [cited by applicant]
US 20150253341A1 · McAvoy et al. · 2015 [cited by applicant]
US 20150266947A1 · Sierks et al. · 2015 [cited by applicant]
US 20150344553A1 · Weinreb et al. · 2015 [cited by applicant]
US 20160031976A1 · Seubert et al. · 2016 [cited by applicant]
US 20160289309A1 · Griswold-Prenner et al. · 2016 [cited by applicant]
US 20160376341A1 · Adolfsson et al. · 2016 [cited by applicant]
US 20170355756A1 · Julien et al. · 2017 [cited by applicant]
US 20180142007A1 · Novak et al. · 2018 [cited by applicant]
US 20180209994A1 · Lannfelt et al. · 2018 [cited by applicant]
US 20190322728A1 · Seubert et al. · 2019 [cited by applicant]
US 20190330314A1 · Barbour et al. · 2019 [cited by applicant]
US 20190330316A1 · Barbour et al. · 2019 [cited by applicant]
US 20200030445A1 · John et al. · 2020 [cited by applicant]
US 20200123239A1 · Seubert et al. · 2020 [cited by applicant]
US 20200131255A1 · Kerchner et al. · 2020 [cited by applicant]
US 20200181245A1 · Masliah et al. · 2020 [cited by applicant]
US 20210023216A1 · Angstenberger et al. · 2021 [cited by applicant]
US 20210032319A1 · Seubert et al. · 2021 [cited by applicant]
US 20210130449A1 · Barbour et al. · 2021 [cited by applicant]
US 20210261652A1 · Nijjar et al. · 2021 [cited by applicant]
US 20230250161A1 · Barbour · 2023 [cited by examiner]
CN 103339146 · 2013 [cited by applicant]
CN 104185640 · 2014 [cited by applicant]
EP 0673418B1 · 1998 [cited by applicant]
EP 1355949B1 · 2010 [cited by applicant]
EP 3080611B1 · 2018 [cited by applicant]
GB 2220211 · 1990 [cited by applicant]
JP 2009056790A · 2009 [cited by applicant]
JP 2010511388A · 2010 [cited by applicant]
JP 2011501655A · 2011 [cited by applicant]
JP 2011521623A · 2011 [cited by applicant]
JP 2012500020A · 2012 [cited by applicant]
JP 2014530597A · 2014 [cited by applicant]
JP 2015520685A · 2015 [cited by applicant]
JP 2015530971 · 2015 [cited by applicant]
JP 2016512551A · 2016 [cited by applicant]
WO WO9110741 · 1991 [cited by applicant]
WO WO9117271 · 1991 [cited by applicant]
WO WO9201047 · 1992 [cited by applicant]
WO WO9220791 · 1992 [cited by applicant]
WO WO9312227 · 1993 [cited by applicant]
WO WO9412629 · 1994 [cited by applicant]
WO WO9507707 · 1995 [cited by applicant]
WO WO199615452A1 · 1996 [cited by applicant]
WO WO9634625 · 1996 [cited by applicant]
WO WO9823635 · 1998 [cited by applicant]
WO WO9840100 · 1998 [cited by applicant]
WO WO00072880 · 2000 [cited by applicant]
WO WO03057838 · 2003 [cited by applicant]
WO WO2004050884 · 2004 [cited by applicant]
WO WO2005019442 · 2005 [cited by applicant]
WO WO2008012142 · 2008 [cited by applicant]
WO WO2008081008 · 2008 [cited by applicant]
WO WO2008103472 · 2008 [cited by applicant]
WO WO2008107388 · 2008 [cited by applicant]
WO WO2009027471 · 2009 [cited by applicant]
WO WO2009134711A1 · 2009 [cited by applicant]
WO WO2011053565A2 · 2011 [cited by applicant]
WO WO2011154321A1 · 2011 [cited by applicant]
WO WO2012049570A1 · 2012 [cited by applicant]
WO WO2013004717A1 · 2013 [cited by applicant]
WO WO2013007839A1 · 2013 [cited by applicant]
WO WO2013028810A1 · 2013 [cited by applicant]
WO WO2013041962A1 · 2013 [cited by applicant]
WO WO2013151762A1 · 2013 [cited by examiner]
WO WO2014008404A1 · 2014 [cited by applicant]
WO WO20141006000A2 · 2014 [cited by applicant]
WO WO2014152157A2 · 2014 [cited by applicant]
WO WO2014165271A2 · 2014 [cited by applicant]
WO WO2014165271A3 · 2014 [cited by applicant]
WO WO2015197823A3 · 2016 [cited by applicant]
WO WO2016079597A1 · 2016 [cited by applicant]
WO WO2016137950A1 · 2016 [cited by applicant]
WO 2016196726A1 · 2016 [cited by applicant]
WO WO2015200806A1 · 2016 [cited by applicant]
WO WO2016196726A9 · 2016 [cited by applicant]
WO WO2017005732A1 · 2017 [cited by applicant]
WO WO2017062672A2 · 2017 [cited by applicant]
WO WO2017091512 · 2017 [cited by applicant]
WO WO2017191559A1 · 2017 [cited by applicant]
WO WO2017191560A1 · 2017 [cited by applicant]
WO WO2017191561A1 · 2017 [cited by applicant]
WO WO2018017370 · 2018 [cited by applicant]
WO WO2018106781A1 · 2018 [cited by applicant]
WO WO2018107125A1 · 2018 [cited by applicant]
WO WO2018152359A1 · 2018 [cited by applicant]
WO WO2018156250A1 · 2018 [cited by applicant]
WO WO2018178077A1 · 2018 [cited by applicant]
WO WO2018204546A2 · 2018 [cited by applicant]
WO WO2018231254A1 · 2018 [cited by applicant]
WO WO2019094595A2 · 2019 [cited by applicant]
WO WO2019110571A1 · 2019 [cited by applicant]
WO WO2019186276A2 · 2019 [cited by applicant]
WO WO2019207159A1 · 2019 [cited by applicant]
WO WO2020096608A1 · 2020 [cited by applicant]
WO WO2020097561A1 · 2020 [cited by applicant]
WO WO2020106598A1 · 2020 [cited by applicant]
WO WO2020163817A1 · 2020 [cited by applicant]
WO WO2020180819A1 · 2020 [cited by applicant]
WO WO2020193520A1 · 2020 [cited by applicant]
WO WO2021010712A1 · 2021 [cited by applicant]
Nohubara et al. Tau Antibody Targeting Pathological Species Blocks Neuronal Uptake and Interneuron Propagation of Tau in Vitro. Am J Pathol. Jun. 2017; 187(6):1399-1412. (Year: 2017). [cited by examiner]
Almagro et al. Progress and Challenges in the Design and Clinical Development of Antibodies for Cancer Therapy. Front Immunol. Jan. 4, 2018;8:1751 (Year: 2008). [cited by examiner]
Gonzales et al., “Minimizing the Immunogenicity of Antibodies for Clinical Application,” Tumour Biol., Jan./Feb. 2005, 26(1):31-43. [cited by applicant]
Kunik et al., “Structural consensus among antibodies defines the antigen binding site,” PLoS Comput Biol., Feb. 23, 2012, 8(2):e1002388, 12 pages. [cited by applicant]
Panka et al., “Variable region framework differences result in decreased or increased affinity of variant anti-digoxin antibodies,” Proc Natl Acad Sci USA, May 1988, 85(9):3080-4. [cited by applicant]
Sela-Culang et al., “The Structural Basis of Antibody-Antigen Recognition,” Front. Immunol., Oct. 8, 2013, 4:302, 13 pages. [cited by applicant]
Wark et al., et al., “Latest technologies for the enhancement of antibody affinity,” Adv. Drug Deliv. Rev., Aug. 7, 2006, 58(5-6):657-670. [cited by applicant]
Goedert, et al., “Cloning and sequencing of the cDNA encoding a core protein of the paired helical filament of Alzheimer disease: Identification as the microtubule-associated protein tau” Proc. Natl. Acad. Sci. USA, vol… [cited by applicant]
PCT/US2014/025044 International Search Report and Written Opinion mailed Nov. 3, 2014. [cited by applicant]
Vigo-Pelfrey, et al., “Elevation of microtubule-associated protein tau in the cerebrospinal fluid of patients with Alzheimer's disease”, [cited by applicant]
PCT/US2014/025044 Invitation to Pay Additional Fees and, Where Applicable, Protest Fee mailed Aug. 15, 2014. [cited by applicant]
EP 14778358.2 European Supplementary Search Report completed Nov. 3, 2016. [cited by applicant]
Castillo-Carranza, et al., “Tau aggregates as immunotherapeutic targets,” [cited by applicant]
Ghoshal, et al., “Tau Conformational Changes Correspond to Impairments of Episodic Memory in Mild Cognitive Impairment and Alzheimer's Disease,” [cited by applicant]
Jicha, et al., “Sequence Requirements for Formation of Conformational Variants of Tau Similar to Those Found in Alzheimer's Disease,” [cited by applicant]
Morris, “Epitope Mapping of Protein Antigens by Competition ELISA,” [cited by applicant]
Dubel, “Molecular Engineering I: Humanization,” [cited by applicant]
Yanamandra, et al., “Anti-Tau Antibodies that Block Tau Aggregate Seeding In Vitro Markedly Decrease Pathology and Improve Cognition in Vivo,” [cited by applicant]
PCT/US2014/025044 International Preliminary Report on Patentability completed Oct. 9, 2014. [cited by applicant]
U.S. Appl. No. 14/776,724 Restriction Requirement mailed Jan. 19, 2017. [cited by applicant]
U.S. Appl. No. 14/776,724 Non-Final Office Action mailed Jun. 1, 2017. [cited by applicant]
Chen, et al., “Enhancement and destruction of antibody function by somatic mutation: unequal occurrence is controlled by V gene combinatorial associations,” [cited by applicant]
Kussie, et al., “A Single Engineered Amino Acid Substitution Changes Antibody Fine Specificity,” [cited by applicant]
Oddo, et al., “Reduction of Soluble Aβ and Tau, but Not Soluble Aβ Alone, Ameliorates Cognitive Decline in Transgenic Mice with Plaques and Tangles,” [cited by applicant]
Hasegawa, et al., “Characterization of Two distinct Monoclonal Antibodies to Paired Helical Filaments: Further Evidence for Fetal-Type Phosphorylation of the T in Paired Helical Filaments”, Journal of Neurochemistry, vo… [cited by applicant]
Leger, et al., “Antibody Drug Discovery Chapter 1: Humanization of Antibodies”, Molecular medicine and Medicinal Chemistry, pp. 1-23 XP055119233 (Jan. 1, 2011). [cited by applicant]
Almagro, et al., “Humanization of antibodies”, [cited by applicant]
Lazar, et al., “A molecular immunology approach to antibody humanization and functional optimization”, [cited by applicant]
Wu, et al., “Simultaneous Humanization and Affinity Optimization of Monoclonal Antibodies”, [cited by applicant]
PCT/IB2017/052544 Search Report and Written Opinion mailed Jul. 31, 2017. [cited by applicant]
PCT/IB2017/052545 Search Report and Written Opinion mailed Aug. 1, 2017. [cited by applicant]
Bacskai, et al., “Imaging of amyloid-β deposits in brains of living mice permits direct observation of clearance of plaques with immunotherapy,” [cited by applicant]
PCT/IB2017/052544 Search Report and Written Opinion mailed Jul. 19, 2017. [cited by applicant]
Agadjanyan, et al., “Humanized monoclonal antibody armanezumab specific to N-terminus of pathological tau: characterization and therapeutic potency,” [cited by applicant]
Kontsekova, et al., “First-in-man tau vaccine targeting structural determinants essential for pathological tau-tau interaction reduces tau oligomerisation and neurofibrillary degeneration in an Alzheimer's disease model… [cited by applicant]
Rosseels, et al., “Tau Monoclonal Antibody Generation Based on Humanized Yeast Models,” [cited by applicant]
PCT/IB2017/052543 International Report on Patentability issued Nov. 6, 2018. [cited by applicant]
PCT/IB2017/052544 International Report on Patentability issued Nov. 6, 2018. [cited by applicant]
PCT/IB2017/052545 International Report on Patentability issued Nov. 6, 2018. [cited by applicant]
U.S. Appl. No. 14/776,724 Final Office Action mailed Oct. 31, 2018. [cited by applicant]
U.S. Appl. No. 14/776,724 Advisory Action mailed Mar. 12, 2019. [cited by applicant]
U.S. Appl. No. 14/776,724 Notice of Allowance mailed Apr. 10, 2019. [cited by applicant]
PCT/US2018/030739 International Search Report and Written Opinion mailed Nov. 5, 2018. [cited by applicant]
PCT/US2018/059895 International Search Report and Written Opinion mailed Apr. 12, 2019. [cited by applicant]
PCT/US2018/030739 International Search Report and Written Opinion mailed Sep. 18, 2018. [cited by applicant]
U.S. Appl. No. 14/776,724 Notice of Allowance mailed Jul. 29, 2019. [cited by applicant]
U.S. Appl. No. 16/091,060 Restriction Requirement mailed Sep. 17, 2019. [cited by applicant]
U.S. Appl. No. 16/092,439 Notice of Allowance mailed Oct. 16, 2019. [cited by applicant]
Pedersen, et al., “Tau immunotherapy for Alzheimer's disease,” Trends in Molecular Medicine, vol. 21, No. 6, pp. 394-402, (Jun. 2015). [cited by applicant]
PCT/US2018/030739 International Preliminary Report on Patentability mailed Nov. 5, 2019. [cited by applicant]
U.S. Appl. No. 16/097,445 Restriction Requirement mailed Feb. 18, 2020. [cited by applicant]
U.S. Appl. No. 16/091,060 Non-Final Office Action mailed Feb. 21, 2020. [cited by applicant]
U.S. Appl. No. 16/092,439 Notice of Allowance and Interview Summary mailed Apr. 10, 2020. [cited by applicant]
PCT/US2019/060616 International Search Report and Written Opinion mailed Mar. 20, 2020. [cited by applicant]
PCT/US2020/017357 Invitation to Pay Additional Fees mailed Apr. 23, 2020. [cited by applicant]
U.S. Appl. No. 16/097,445 Non-Final Office Action mailed May 27, 2020. [cited by applicant]
PCT/US2020/017357 International Search Report and Written Opinion mailed Jun. 17, 2020. [cited by applicant]
Kawahara, et al., “The Novel Monoclonal Antibody 9F5 Reveals Expression of a Fragment of GPNMB/Osteoactivin Processed by Furin-like Protease(s) in a Subpopulation of Microglia in Neonatal Rat Brain,” GLIA, vol. 64, No. … [cited by applicant]
Strang, et al., “Generation and characterization of new monoclonal antibodies targeting the PHF1 and AT8 epitopes on human tau,” Acta Neuropathologica Communications, 5:58, (2017). [cited by applicant]
Croft, et al., “Novel monoclonal antibodies targeting the microtubule-binding domain of human tau,” PLoS ONE, 13(4): e0195211, (Apr. 2018). [cited by applicant]
PCT/US2020/020704 Invitation to Pay Additional Fees mailed Jun. 3, 2020. [cited by applicant]
EP 19213368 Extended European Search Report mailed Jun. 24, 2020. [cited by applicant]
Florenzano, et al., “Extracellular truncated tau causes early presynaptic dysfunction associated with Alzheimer's disease and other tauopathies,” Oncotarget, vol. 8, No. 29, pp. 64745-46778, (Apr. 2017). [cited by applicant]
Gershoni, et al., “Epitope Mapping, The First Step in Developing Epitope-Based Vaccines,” Biodrugs, 21:(3), p. 145-156. (2007). [cited by applicant]
PCT/US2020/020704 Search Report and Written Opinion mailed Aug. 4, 2020. [cited by applicant]
U.S. Appl. No. 16/091,060 Notice of Allowance and Interview Summary mailed Aug. 19, 2020. [cited by applicant]
U.S. Appl. No. 16/097,445 Corrected Notice of Allowance mailed Oct. 6, 2020. [cited by applicant]
U.S. Appl. No. 16/097,445 Notice of Allowance mailed Oct. 2, 2020. [cited by applicant]
EP 18795047 Extended European Search Report mailed Feb. 2, 2021. [cited by applicant]
U.S. Appl. No. 16/667,647 Restriction Requirement mailed Jan. 13, 2021. [cited by applicant]
U.S. Appl. No. 16/808,209 Notice of Allowance mailed Dec. 31, 2020. [cited by applicant]
PCT/US2018/059895 International Preliminary Report on Patentability mailed May 11, 2021. [cited by applicant]
PCT/US2019/060616 International Preliminary Report on Patentability mailed May 11, 2021. [cited by applicant]
U.S. Appl. No. 16/667,647 Non-Final Office Action mailed Jun. 28, 2021. [cited by applicant]
Ladner, “Mapping the Epitopes of Antibodies,” Biotechnology and Genetic Engineering Reviews, vol. 24, 1-30, (2007). [cited by applicant]
PCT/US2020/017357 International Preliminary Report on Patentability mailed Aug. 10, 2021. [cited by applicant]
PCT/US2020/020704 International Preliminary Report on Patentability mailed Aug. 25, 2021. [cited by applicant]
Yanamandra et al., “Anti-tau antibody reduces insoluble tau and decreases brain atrophy,” Annals of Clinical and Translational Neurology 2, 278-288 (2015). [cited by applicant]
U.S. Appl. No. 16/933,792 Non-Final Office Action mailed Dec. 15, 2021. [cited by applicant]
Alexander et al., “Development of High Potency Universal DR-Restricted Helper Epitopes by Modification of High Affinity DR-Blocking Peptides,” Immunity, Dec. 1994, 1:751-761. [cited by applicant]
Andreadis et al., “Structure and novel exons of the human .tau. gene,” Biochemistry, 1992, 31:10626-10633. [cited by applicant]
Atwal et al., “A Therapeutic Antibody Targeting BACE1 Inhibits Amyloid-β Production in Vivo,” Sci. Translation Med., May 2011, 84(3):1-12. [cited by applicant]
Banner et al., “Mapping the conformational space accessible to BACE2 using surface mutants and cocrystals with Fab fragments, Fynomers and Xaperones,” Acta. Crystallogr. D. Biol. Crystallogr., 2013, 69(Pt6): 1124-1137. [cited by applicant]
Bertschinger et al., “Selection of single domain binding proteins by covalent DNA display,” Protein Eng. Des. Sel., Feb. 2007, 20:57-68. [cited by applicant]
Bett et al., “Packaging Capacity and Stability of Human Adenovirus Type 5 Vectors,” J. Virol., 1993, 67:5911-5921. [cited by applicant]
Boris-Lawrie et al., “Recent advances in retrovirus vector technology,” Current Opinion in Genetics & Development, Feb. 1993, 3(1):102-109. [cited by applicant]
Brack et al., “A bispecific HER2-targeting FynomAb with superior antitumor activity and novel mode of action,” Mol. Cancer Ther., 2014, 13:2030-2039. [cited by applicant]
Chicz et al., “Specificity and promiscuity among naturally processed peptides bound to HLA-DR alleles,” J. Exp. Med., Jul. 1993, 178(1):27-47. [cited by applicant]
Chothia et al., “Canonical structures for the hypervariable regions of immunoglobulins,” Journal of Molecular Biology, Aug. 1987, 196(4):901-917. [cited by applicant]
Chothia et al., “Conformations of immunoglobulin hypervariable regions,” Nature, Dec. 1989, 342:878-883. [cited by applicant]
Co et al., “Chimeric and humanized antibodies with specificity for the CD33 antigen,” J. Immunol., Feb. 1992, 148(4): 1149-1154. [cited by applicant]
Dafferner et al., “Immunopurification of Acetylcholinesterase from Red Blood Cells for Detection of Nerve Agent Exposure,” Chemical Research in Toxicology, 2017, 30(10):1897-1910. [cited by applicant]
Deshpande et al., “The RCSB Protein Data Bank: a redesigned query system and relational database based on the mmCIF schema,” Nucleic Acids Res., Jan. 2005, 33:D233-D237. [cited by applicant]
Dubensky et al., “Sindbis virus DNA-based expression vectors: utility for in vitro and in vivo gene transfer,” J. Virol., Jan. 1996, 70(1):508-519. [cited by applicant]
Edelman et al., “The Covalent Structure of an Entire y G Immunoglobulin Molecule,” Proc. Natl. Acad. USA, May 1969, 63(1)78-85. [cited by applicant]
Extended European Search Report in European AppIn No. 19881978.1, dated Jul. 12, 2022, 9 pages. [cited by applicant]
Falk et al., “Pool sequencing of natural HLA-DR, DQ, and DP ligands reveals detailed peptide motifs, constraints of processing, and general rules,” Immunogenetics, 1994, 39:230-242. [cited by applicant]
Foote et al., “Antibody framework residues affecting the conformation of the hypervariable loops,” Journal of Molecular Biology, Mar. 1992, 224(2):487-499. [cited by applicant]
Friden et al., “Anti-transferrin receptor antibody and antibody-drug conjugates cross the blood-brain barrier,” Proc. Natl. Acad Sci. USA, Jun. 1991, 88(11):4771-4775. [cited by applicant]
Friden et al., “Blood-Brain Barrier Penetration and in Vivo Activity of an NGF Conjugate,” Science, Jan. 1993, 259(5093):373-377. [cited by applicant]
GenBank Accession No. AAZ09048.1, “immunoglobulin kappa light chain variable region, partial [ [cited by applicant]
GenBank Accession No. ARX71335.1, “anti-human acetylcholinesterase immunoglobulin light chain variable region, partial [ [cited by applicant]
GenBank Accession No. BAC01986.1, “immunoglobulin heavy chain VHDJ region, partial [ [cited by applicant]
Goedert et al., “Cloning and sequencing of the cDNA encoding an isoform of microtubule-associated protein tau containing four tandem repeats: differential expression of tau protein mRNAs in human brain,” EMBO J., 1989, … [cited by applicant]
Goedert et al., “Multiple isoforms of human microtubule-associated protein tau: sequences and localization in neurofibrillary tangles of Alzheimer's disease,” Neuron, Oct. 1989, 3(4):519-526. [cited by applicant]
Gonzales et al., “SDR grafting of a murine antibody using multiple human germline templates to minimize its immunogenicity,” Mol. Immunol., Jul. 2004, 41(9):863-872. [cited by applicant]
Grabulovski et al., “A Novel, Non-immunogenic Fyn SH3-derived Binding Protein with Tumor Vascular Targeting Properties,” J Biol. Chem., Feb. 2007, 282(5):3196-3204. [cited by applicant]
Hammer et al., “Promiscuous and allele-specific anchors in HLA-DR-binding peptides,” Cell, Jul. 1993, 74(1):197-203. [cited by applicant]
Hazra et al., “Linking radiosilver to monoclonal antibodies reduced by ascorbic acia,” Cell Biophys., Jan. 1994, 24-25:1-7. [cited by applicant]
Hinton et al., “Engineered Human IgG Antibodies with Longer Serum Half-lives in Primates,” J. Biol. Chem., Feb. 2004, 279(8):6213-6216. [cited by applicant]
Ittner et al., “Parkinsonism and impaired axonal transport in a mouse model of frontotemporal dementia,” Proc. Natl. Acad. Sci. USA, Oct. 2008, 105(41):15997-16002. [cited by applicant]
Iwahashi et al., “CDR substitutions of a humanized monoclonal antibody (CC49): contributions of individual CDRs to antigen binding and immunogenicity,” Mol. Immunol., 1999, 36(15-16): 1079-1091. [cited by applicant]
Jack et al., “Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade,” The Lancet Neurology, Jan. 2010, 9(1):119-128. [cited by applicant]
Jones et al., “The INNs and outs of antibody nonproprietary names,” mAbs, 2016, 8(1):1-9. [cited by applicant]
Junghans et al., “Anti-Tac-H, a Humanized Antibody to the Interleukin 2 Receptor with New Features for Immunotherapy in Malignant and Immune Disorders,” Cancer Res., Mar. 1990, 50(5): 1495-1502. [cited by applicant]
Khlistunova et al., “Inhibition of Tau Aggregation in Cell Models of Tauopathy,” Current Alzheimer Research, 2007, 4(5):544-546. [cited by applicant]
Kostelny et al., “Formation of a bispecific antibody by the use of leucine zippers,” Journal of Immunology, Mar. 1992, 148(5):1547-1553. [cited by applicant]
Lazar et al., “Engineered antibody Fc variants with enhanced effector function,” Proc. Natl. Acad. Sci. USA, Mar. 2006, 103(11):4005-4010. [cited by applicant]
Lee et al., “The microtubule binding domain of tau protein,” Neuron, Jun. 1989, 2(6):1615-1624. [cited by applicant]
Lefranc et al., “IMGT unique numbering for immunoglobulin and T cell receptor constant domains and Ig superfamily C-like domains,” Dev. Comp. Immunol., 2005, 29(3):185-203. [cited by applicant]
Lewis et al., “Neurofibrillary tangles, amyotrophy and progressive motor disturbance in mice expressing mutant (P301L) tau protein,” Nature Genetics, 2000, 25:402-405. [cited by applicant]
Liu et al., “N-terminal Glutamate to Pyroglutamate Conversion in Vivo for Human IgG2 Antibodies,” J. Biol. Chem., Apr. 2011, 286(13):11211-11217. [cited by applicant]
Martin et al., “Structural Families in Loops of Homologous Proteins: Automatic Classification, Modelling and Application to Antibodies,” Journal of Molecular Biology, Nov. 1996, 263(5):800-815. [cited by applicant]
McGee et al., “The encapsulation of a model protein in poly (D, L lactide-co-glycolide) microparticles of various sizes: an evaluation of process reproducibility,” Journal of Microencapsulation, 1997, 14(2):197-210. [cited by applicant]
Neuberger, “Generating high-avidity human mabs in mice,” Nat. Biotechnol., 1996, 14:826. [cited by applicant]
Ohe et al., “Construction of a Novel Bovine Papillomavirus Vector Without Detectable Transforming Activity Suitable for Gene Transfer,” Human Gene Therapy, 1995, 6(3):325-333. [cited by applicant]
Ostberg et al., “Human X (Mouse X Human) Hybridomas Stably Producing Human Antibodies,” Hybridoma, 1983, 2(4):361-367. [cited by applicant]
Padlan, “A possible procedure for reducing the immunogenicity of antibody variable domains while preserving their ligand-binding properties,” Mol. Immunol., 1991, 28(4-5):489-498. [cited by applicant]
Pascalis et al., “Grafting of “Abbreviated” Complementarity-Determining Regions Containing Specificity-Determining Residues Essential for Ligand Contact to Engineer a Less Immunogenic Humanized Monoclonal Antibody,” J I… [cited by applicant]
Piechotta et al., “Structural and functional analyses of pyroglutamate-amyloid-β-specific antibodies as a basis for Alzheimer immunotherapy,” Journal of Biological Chemistry, Jul. 2017, 292(30):12713-12724. [cited by applicant]
Pietersz et al., “Novel Synthesis and in Vitro Characterization of Disulfide-linked Ricin-Monoclonal Antibody Conjugates Devoid of Galactose Binding Activity,” Cancer Research, Aug. 1988, 48(16):4469-4476. [cited by applicant]
Polito et al., “The conjugate Rituximab/saporin-S6 completely inhibits clonogenic growth of CD20-expressing cells and produces a synergistic toxic effect with Fludarabine,” Leukemia, 2004, 18:1215-1222. [cited by applicant]
Poorkaj et al., “Tau is a candidate gene for chromosome 17 frontotemporal dementia,” Annals of Neurology, 1998, 43(6):815-825. [cited by applicant]
Powilleit et al., “Exploiting the Yeast L-A Viral Capsid for the In Vivo Assembly of Chimeric VLPs as Platform in Vaccine Development and Foreign Protein Expression,” PLoS ONE, May 2007, 2(5):e415. [cited by applicant]
Queen et al., “Cell-Type Specific Regulation of a K Immunoglobulin Gene by Promoter and Enhancer Elements,” Immunol. Rev., Feb. 1986, 89(1):49-68. [cited by applicant]
Schiele et al., “Structure-guided residence time optimization of a dabigatran reversal agent,” mAbs, 2015, 7(5):871-880. [cited by applicant]
Schilling et al., “Glutaminyl cyclases from animals and plants: a case of functionally convergent protein evolution,” Biol. Chem., Aug. 2008, 389(8):983-991. [cited by applicant]
Schlatter et al., “Generation, characterization and structural data of chymase binding proteins based on the human Fyn kinase SH3 domain,” mAbs, 2012, 4:497-508. [cited by applicant]
Sinigaglia et al., “A malaria T-cell epitope recognized in association with most mouse and human MHC class II molecules,” Nature, Dec. 1988, 336:778-780. [cited by applicant]
Songsivilai et al., “Bispecific antibody: a tool for diagnosis and treatment of disease,” Clin. Exp. Immunol., Mar. 1990, 79(3):315-321. [cited by applicant]
Southwood et al., “Several Common HLA-DR Types Share Largely Overlapping Peptide Binding Repertoires,” J. Immunology, Apr. 1998, 160(7):3363-3373. [cited by applicant]
Stoute et al., “A Preliminary Evaluation of a Recombinant Circumsporozoite Protein Vaccine against Plasmodium falciparum Malaria,” The New England Journal of Medicine, Jan. 1997, 336(2):86-91. [cited by applicant]
Tamura et al., “Structural Correlates of an Anticarcinoma Antibody: Identification of Specificity-Determining Residues (SDRs) and Development of a Minimally Immunogenic Antibody Variant by Retention of SDRs Only,” The J… [cited by applicant]
Thorpe et al., “The Preparation and Cytotoxic Properties of Antibody-Toxin Conjugates,” Immunological Reviews, Feb. 1982, 62(1):119-158. [cited by applicant]
UniProt Accession No. P10636, “Microtubule-associated protein tau,” Jan. 16, 2019, 32 pages. [cited by applicant]
Vajdos et al., “Comprehensive Functional Maps of the Antigen-binding Site of an Anti-ErbB2 Antibody Obtained with Shotgun Scanning Mutagenesis,” Journal of Molecular Biology, Jul. 2002, 320(2):415-428. [cited by applicant]
Wang et al., “Two-Stage PCR Protocol Allowing Introduction of Multiple Mutations, Deletions and Insertions Using QuikChangeTM Site-Directed Mutagenesis,” BioTechniques, 1999, 26(4):680-682. [cited by applicant]
Wedemayer et al., “Structural Insights into the Evolution of an Antibody Combining Site,” Science, Jun. 1997, 276(5319):1665-1669. [cited by applicant]
who.int [online], “International Nonproprietary Names (INN) for biological and biotechnological substances (a review),” available on or before Aug. 24, 2015, via Internet Archive: Wayback Machine URL <https://web.archiv… [cited by applicant]
Witzig, “Radioimmunotherapy for patients with relapsed B-cell non-Hodgkin lymphoma,” Cancer Chemotherapy and Pharmacology, Jul. 2001, 48:S91-S95. [cited by applicant]
Wu et al., “Generation and Characterization of a Dual Variable Domain Immunoglobulin (DVD-Ig™) Molecule,” Antibody Engineering, 2010, 2:239-250. [cited by applicant]
Xiao et al., “High Efficiency, Long-Term Clinical Expression of Cottontail Rabbit Papillomavirus (CRPV) DNA in Rabbit Skin Following Particle-Mediated DNA Transfer,” Nucleic Acids. Res., Jul. 1996, 24(13):2620-2622. [cited by applicant]
Yu et al., “Boosting Brain Uptake of a Therapeutic Antibody by Reducing Its Affinity for a Transcytosis Target,” Sci. Trans. Med., May 2011, 3(84):84ra44. [cited by applicant]
Zhou et al., “Adeno-associated virus 2-mediated high efficiency gene transfer into immature and mature subsets of hematopoietic progenitor cells in human umbilical cord blood,” J. Exp. Med., Jun. 1994, 179(6):1867-1875. [cited by applicant]
Office Action in Chinese Appln. No. 201980073684.9, mailed on Dec. 14, 2023, 18 pages (with Machine translation). [cited by applicant]