IP Library Granted Patent US 12,365,743
Granted Patent B2
US 12,365,743 · App. 18/172,987 · Granted Jul 22, 2025

Anti-CD28 x anti-PSMA antibodies

Inventors: John R. Desjarlais (Pasadena, CA); Gregory Moore (Azusa, CA); Michael Hedvat (Encino, CA); Juan Diaz (Anaheim Hills, CA); Veronica Gusti Zeng (Duarte, CA); Matthew Adam Dragovich (Monrovia, CA); Joseph Erhardt (Sellersville, PA); Theresa McDevitt (Warminster, PA); Fouad Moussa (Allentown, PA); Pankaj Seth (Norristown, PA); Fei Shen (Collegeville, PA); Adam Zwolak (Bala Cynwyd, PA)
Assignee: Xencor, Inc.
C07K16/468C07K16/2818C07K16/3069C07K2317/31C07K2317/565C07K2317/622
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 12,365,743
App. No.
18/172,987
Granted
Jul 22, 2025
Kind
B2
Abstract

Provided herein are novel anti-CD28× anti-PSMA antibodies and methods of using such antibodies for the treatment of PSMA-associated cancers. Subject anti-CD28× anti-PSMA antibodies are capable of agonistically binding to CD28 costimulatory molecules on T cells and PSMA on tumor cells. Thus, such antibodies selectively enhance anti-tumor activity at tumor sites while minimizing peripheral toxicity. The subject antibodies provided herein are particularly useful in combination with other anti-cancer therapies (e.g., anti-CD3× anti-PSMA antibodies) for the treatment of prostate cancers.

Claims (10)

1. A heterodimeric antibody comprising:

a) a first monomer comprising:

i) a single chain variable fragment (scFv); and

ii) a first Fc domain, wherein the scFv is covalently attached to the N-terminus of the first Fc domain using a domain linker;

b) a second monomer comprising, from N-terminal to C-terminal, a VH1-CH1-hinge-CH2-CH3, wherein VH1 is a first variable heavy domain and CH2-CH3 is a second Fc domain; and

c) a light chain comprising, from N-terminal to C-terminal, VL1-CL, wherein VL1 is a first variable light domain and CL is a constant light domain,

wherein the scFv comprises a second VH domain (VH2), a scFv linker, and a second variable light domain (VL2),

wherein the VH1 and the VL1 together form a first antigen binding domain (ABD) and the VH2 and the VL2 together form a second ABD, and

wherein the first ABD binds Prostate Specific Membrane Antigen (PSMA) and the second ABD binds CD28, and

wherein the VH1 has an amino acid sequence of SEQ ID NO: 214, the VH2 has an amino acid sequence of SEQ ID NO: 396, the VL1 has an amino acid of SEQ ID NO: 218, and the VL2 has an amino acid sequence of SEQ ID NO: 400.

Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 3, 2023
From: JANSSEN RESEARCH & DEVELOPMENT, LLC
To: JANSSEN BIOTECH, INC.
Reel/Frame 063524/0914 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 3, 2023
From: DESJARLAIS, JOHN R.; MOORE, GREGORY; HEDVAT, MICHAEL; DIAZ, JUAN; GUSTI ZENG, VERONICA; DRAGOVICH, MATTHEW ADAM
To: XENCOR, INC.
Reel/Frame 063529/0805 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 3, 2023
From: ERHARDT, JOSEPH; MCDEVITT, THERESA; MOUSSA, FOUAD; SETH, PANKAJ; SHEN, FEI; ZWOLAK, ADAM
To: JANSSEN RESEARCH & DEVELOPMENT, LLC
Reel/Frame 063529/0964 →
Continuity (2)
Provisional Application 63313233 · Feb 23, 2022
Related Publication 20230265218A1 · Aug 24, 2023
References Cited (238)
US 5601819A · Wong et al. · 1997 [cited by applicant]
US 6551592B2 · Lindhofer et al. · 2003 [cited by applicant]
US 6699715B1 · Ledbetter et al. · 2004 [cited by applicant]
US 6881557B2 · Foote · 2005 [cited by applicant]
US 6994853B1 · Lindhofer et al. · 2006 [cited by applicant]
US 7538196B2 · Jung · 2009 [cited by applicant]
US 8709421B2 · Heiss et al. · 2014 [cited by applicant]
US 9017676B2 · Lindhofer · 2015 [cited by applicant]
US 9382329B2 · Chang et al. · 2016 [cited by applicant]
US 9441034B2 · Sivakumar · 2016 [cited by examiner]
US 10208119B2 · Fang et al. · 2019 [cited by applicant]
US 10227410B2 · Moore et al. · 2019 [cited by applicant]
US 10259887B2 · Bernett et al. · 2019 [cited by applicant]
US 10294300B2 · Raum et al. · 2019 [cited by applicant]
US 10364287B2 · Mary et al. · 2019 [cited by applicant]
US 10428155B2 · Moore et al. · 2019 [cited by applicant]
US 10517949B2 · Wang et al. · 2019 [cited by applicant]
US 10669337B2 · Irving et al. · 2020 [cited by applicant]
US 10752697B2 · Park · 2020 [cited by examiner]
US 11370828B2 · Westendorf · 2022 [cited by examiner]
US 11396544B2 · Murphy et al. · 2022 [cited by applicant]
US 11591401B2 · Desjarlais · 2023 [cited by examiner]
US 11623957B2 · Moore et al. · 2023 [cited by applicant]
US 11913023B2 · Boyle et al. · 2024 [cited by applicant]
US 11919956B2 · Desjarlais et al. · 2024 [cited by applicant]
US 12037604B2 · Boyle et al. · 2024 [cited by applicant]
US 20010001310A1 · Weiner et al. · 2001 [cited by applicant]
US 20020076406A1 · Leung · 2002 [cited by applicant]
US 20020103345A1 · Zhu · 2002 [cited by applicant]
US 20020115134A1 · Jung · 2002 [cited by applicant]
US 20030185832A1 · Thorpe · 2003 [cited by applicant]
US 20040253250A1 · Ledbetter et al. · 2004 [cited by applicant]
US 20050079170A1 · Le Gall et al. · 2005 [cited by applicant]
US 20050175606A1 · Huang et al. · 2005 [cited by applicant]
US 20060115481A1 · Lindhofer et al. · 2006 [cited by applicant]
US 20060188493A1 · Thomas · 2006 [cited by applicant]
US 20070036783A1 · Humeau et al. · 2007 [cited by applicant]
US 20070212350A1 · Govindan et al. · 2007 [cited by applicant]
US 20080145362A1 · Kipriyanov et al. · 2008 [cited by applicant]
US 20080299137A1 · Svendsen et al. · 2008 [cited by applicant]
US 20080305105A1 · Kufer et al. · 2008 [cited by applicant]
US 20090117108A1 · Wang et al. · 2009 [cited by applicant]
US 20090246204A1 · Hunig · 2009 [cited by applicant]
US 20100291112A1 · Kellner et al. · 2010 [cited by applicant]
US 20100322933A1 · Lindhofer et al. · 2010 [cited by applicant]
US 20100330034A1 · Bigler et al. · 2010 [cited by applicant]
US 20110189735A1 · Hanke et al. · 2011 [cited by applicant]
US 20110313135A1 · Vanhove et al. · 2011 [cited by applicant]
US 20130078236A1 · Mary et al. · 2013 [cited by applicant]
US 20140348839A1 · Chowdhury et al. · 2014 [cited by applicant]
US 20150119555A1 · Jung et al. · 2015 [cited by applicant]
US 20160137980A1 · Abbot et al. · 2016 [cited by applicant]
US 20160355608A1 · Bernett et al. · 2016 [cited by applicant]
US 20170335016A1 · Takahashi · 2017 [cited by applicant]
US 20180079798A1 · Protzer et al. · 2018 [cited by applicant]
US 20180112000A1 · Nolle et al. · 2018 [cited by applicant]
US 20180118836A1 · Bernett et al. · 2018 [cited by applicant]
US 20180127501A1 · Bernett et al. · 2018 [cited by applicant]
US 20190106504A1 · Wu et al. · 2019 [cited by applicant]
US 20190233534A1 · Mehlin et al. · 2019 [cited by applicant]
US 20190375852A1 · Lindhofer et al. · 2019 [cited by applicant]
US 20190389951A1 · Murphy et al. · 2019 [cited by applicant]
US 20200024360A1 · Anderson et al. · 2020 [cited by applicant]
US 20200048350A1 · Eckelman et al. · 2020 [cited by applicant]
US 20200071421A1 · Zhou · 2020 [cited by applicant]
US 20200140552A1 · Wu et al. · 2020 [cited by applicant]
US 20200157213A1 · Zhu et al. · 2020 [cited by applicant]
US 20200157222A1 · Fang et al. · 2020 [cited by applicant]
US 20200199233A1 · Murphy et al. · 2020 [cited by applicant]
US 20200199234A1 · Georges et al. · 2020 [cited by applicant]
US 20200239576A1 · Murphy et al. · 2020 [cited by applicant]
US 20200247862A1 · Bernett et al. · 2020 [cited by applicant]
US 20200299388A1 · Skokos et al. · 2020 [cited by applicant]
US 20200376136A1 · Rudge et al. · 2020 [cited by applicant]
US 20210040210A1 · Ganesan et al. · 2021 [cited by applicant]
US 20210047435A1 · Luo et al. · 2021 [cited by applicant]
US 20210171596A1 · Moore et al. · 2021 [cited by applicant]
US 20220073876A1 · Boyle et al. · 2022 [cited by applicant]
US 20220089766A1 · DiLillo et al. · 2022 [cited by applicant]
US 20220098306A1 · Desjarlais · 2022 [cited by examiner]
US 20220119525A1 · Desjarlais et al. · 2022 [cited by applicant]
US 20220119530A1 · Desjarlais · 2022 [cited by examiner]
US 20220135684A1 · Desjarlais et al. · 2022 [cited by applicant]
US 20220233690A1 · Olson et al. · 2022 [cited by applicant]
US 20230040715A1 · Zwolak et al. · 2023 [cited by applicant]
US 20230137343A1 · Boyle et al. · 2023 [cited by applicant]
US 20230383012A1 · Moore et al. · 2023 [cited by applicant]
US 20240002793A1 · Boyle et al. · 2024 [cited by applicant]
US 20240034995A1 · Boyle et al. · 2024 [cited by applicant]
US 20240059789A1 · McDevitt · 2024 [cited by examiner]
US 20240218082A1 · Desjarlais · 2024 [cited by examiner]
US 20250043001A1 · Moore et al. · 2025 [cited by applicant]
US 20250084179A1 · Bernett et al. · 2025 [cited by applicant]
US 20250084186A1 · Nisthal et al. · 2025 [cited by applicant]
EP 1874821B1 · 2013 [cited by applicant]
EP 3575319A1 · 2019 [cited by applicant]
EP 2981281B1 · 2020 [cited by applicant]
EP 3177645B1 · 2021 [cited by applicant]
WO WO1998004592A1 · 1998 [cited by applicant]
WO WO1999037791A1 · 1999 [cited by applicant]
WO WO200247721A1 · 2002 [cited by applicant]
WO WO2002051871A2 · 2002 [cited by applicant]
WO WO2003048194A2 · 2003 [cited by applicant]
WO WO2003057732A2 · 2003 [cited by applicant]
WO WO2003074566A2 · 2003 [cited by applicant]
WO WO2003078468A2 · 2003 [cited by applicant]
WO WO2004087876A2 · 2004 [cited by applicant]
WO WO2004087876A3 · 2005 [cited by applicant]
WO WO2005095456A1 · 2005 [cited by applicant]
WO WO2009062001A1 · 2009 [cited by applicant]
WO WO2010151792A1 · 2010 [cited by applicant]
WO WO2011097603A1 · 2011 [cited by applicant]
WO WO2012088302A2 · 2012 [cited by applicant]
WO WO2014055897A2 · 2014 [cited by applicant]
WO WO2014110601A1 · 2014 [cited by applicant]
WO WO2014145806A2 · 2014 [cited by applicant]
WO WO2014165818A2 · 2014 [cited by applicant]
WO WO2014165818A3 · 2014 [cited by applicant]
WO WO2015112805A1 · 2015 [cited by applicant]
WO WO2016086186A2 · 2016 [cited by applicant]
WO WO2015112805A8 · 2016 [cited by applicant]
WO WO2016185016A1 · 2016 [cited by applicant]
WO WO2017023761A1 · 2017 [cited by applicant]
WO WO2017100372A1 · 2017 [cited by applicant]
WO WO2017103003A1 · 2017 [cited by applicant]
WO WO2017134158A1 · 2017 [cited by applicant]
WO WO2017205738A1 · 2017 [cited by applicant]
WO WO2017220990A1 · 2017 [cited by applicant]
WO WO2018005706A1 · 2018 [cited by applicant]
WO WO2018059502A1 · 2018 [cited by applicant]
WO WO2018184966A1 · 2018 [cited by applicant]
WO WO2019009726A1 · 2019 [cited by applicant]
WO WO2019016392A1 · 2019 [cited by applicant]
WO WO2019080872A1 · 2019 [cited by applicant]
WO WO2019190327A2 · 2019 [cited by applicant]
WO WO2019197583A1 · 2019 [cited by applicant]
WO WO2019224718A2 · 2019 [cited by applicant]
WO WO2019241758A1 · 2019 [cited by applicant]
WO WO2019245991A1 · 2019 [cited by applicant]
WO WO2020006509A1 · 2020 [cited by applicant]
WO WO2020011868A1 · 2020 [cited by applicant]
WO WO2020014270A1 · 2020 [cited by applicant]
WO WO2020023553A1 · 2020 [cited by applicant]
WO WO2020033702A1 · 2020 [cited by applicant]
WO WO2020076970A1 · 2020 [cited by applicant]
WO WO2020103100A1 · 2020 [cited by applicant]
WO WO2020127618A1 · 2020 [cited by applicant]
WO WO2020132066A1 · 2020 [cited by applicant]
WO WO2020180726A1 · 2020 [cited by applicant]
WO WO2020227515A1 · 2020 [cited by applicant]
WO WO2021026387A2 · 2021 [cited by applicant]
WO WO2021030657A1 · 2021 [cited by applicant]
WO WO2021155071A1 · 2021 [cited by applicant]
WO WO2021155380A1 · 2021 [cited by applicant]
WO WO2021173307A1 · 2021 [cited by applicant]
WO WO2021181233A2 · 2021 [cited by applicant]
WO WO2021197359A1 · 2021 [cited by applicant]
WO WO2021207242A2 · 2021 [cited by applicant]
WO WO2021229507A2 · 2021 [cited by applicant]
WO WO2021231969A1 · 2021 [cited by applicant]
WO WO2021259890A1 · 2021 [cited by applicant]
WO WO2021260064A1 · 2021 [cited by applicant]
WO WO2022040482A1 · 2022 [cited by applicant]
WO WO2022056199A1 · 2022 [cited by applicant]
WO WO2022061098A1 · 2022 [cited by applicant]
WO WO2022081886A1 · 2022 [cited by applicant]
WO WO2022162518A3 · 2022 [cited by examiner]
WO WO2022056197A1 · 2022 [cited by applicant]
WO WO2022162518A2 · 2022 [cited by applicant]
WO WO2022165171A1 · 2022 [cited by applicant]
WO WO2022200443A1 · 2022 [cited by applicant]
WO WO2022201053A1 · 2022 [cited by applicant]
WO WO2023046322A1 · 2023 [cited by applicant]
WO WO2023164627A1 · 2023 [cited by applicant]
WO WO2023164640A1 · 2023 [cited by applicant]
WO WO2025049613A1 · 2025 [cited by applicant]
Stebbings et al., After TGN1412: Recent developments in cytokine release assays., J Immunotoxicol. Jan. 2013; 10(1): 75-82. [cited by applicant]
Waite et al., Tumor-targeted CD28 bispecific antibodies enhance the antitumor efficacy of PD-1 immunotherapy., Sci. Transl. Med. 12, eaba2325 (2020). [cited by applicant]
McCarthy et al. Altering the fine specificity of an anti-Legionella single chain antibody by a single amino acid insertion., J. Immunol. Methods, 251(1-2): 137-149, 2001. [cited by applicant]
Lin et al. Improved affinity of a chicken single-chain antibody to avian infectious bronchitis virus by site-directed mutagenesis of complementarity-determining region H3., African Journal of Biotechnology, 10(79): 1829… [cited by applicant]
Yu, Ph.D, Hangxing, Analyzing antibody sequence for recombinant antibody expression. GenScript, May 20, 2015. [cited by applicant]
Bluemel et al., Epitope distance to the target cell membrane and antigen size determine the potency of T cell-mediated lysis by BiTE antibodies specific for a large melanoma surface antigen., Cancer Immunol Immunother. … [cited by applicant]
Moore et al., A robust heterodimeric Fo platform engineered for efficient development of bispecific antibodies of multiple formats., Methods. Feb. 1, 2019;154:38-50. doi:10.1016/j.ymeth.2018.10.006. Epub Oct. 23, 2018. [cited by applicant]
Brinkmann et al., The making of bispecific antibodies“, MABS, vol. 9, No. 2, Jan. 10, 2017 (Jan. 10, 2017), pp. 182-212”. [cited by applicant]
Moore, Gregory et al., Abstract 1880: PDLI-targeted CD28 costimulatory bispecific antibodies enhance T cell activation in solid tumors., Cancer Research, Jul. 1, 2021 (Jul. 1, 2021), XP055881520, Retrieved from the Inte… [cited by applicant]
Moore, Gregory et al., PDLI-targeted CD28 costimulatory bispecific antibodies enhance T cell activation in solid tumors., Jul. 1, 2021 (Jul. 1, 20211), XP055881523, Retrieved from the Internet: URL:https://investors.xen… [cited by applicant]
Almagro et al., Humanization of antibodies. Front Biosci. Jan. 1, 2008 ;13:1619-33. (Year: 2008). [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. (Year: 1994). [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. (Year: 2003). [cited by applicant]
Mullard, Asher, Trispecific antibodies take to the clinic., Nature Reviews Drug Discovery, Nature, Publishing Group, GB, vol. 19, No. 10, Sep. 11, 2020 (Sep. 11, 2020), pp. 657-658. [cited by applicant]
Singh et al., Overcoming the challenges associated with CD3+ T-cell redirection in cancer., Br J Cancer. Mar. 16, 2021; 124(6): 1037-1048. [cited by applicant]
Majocchi et al., Abstract 2884: Optimized CD28 bispecific antibodies for targeted activation of T cells within the tumor microenvironment., Cancer Res (2022) 82 (12_Supplement): 2884. [cited by applicant]
Poirier et al., CD28-Specific Immunomodulating Antibodies: What Can Be Learned From Experimental Models?: CD28-Specific Immunomodulating Antibodies., American Journal of Transplantation, vol. 12, No. 7, Jul. 1, 2012 (Ju… [cited by applicant]
Liu et al., Bispecific antibody targeting TROP2xCD3 suppresses tumor growth of triple negative breast cancer., J Immunother Cancer. Oct. 2021;9(10):e003468. doi: 10.1136/jitc-2021-003468. [cited by applicant]
Elshiaty et al., Principles and Current Clinical Landscape of Multispecific Antibodies against Cancer., Int J Mol Scl. May 26, 2021;22(11):5632. doi: 10.3390/ijms22115632. [cited by applicant]
Zeng et al., 1073 Costimulatory CD28 trispecific antibodies targeting PDL1 and PDL2 enhance T cell activation in solid tumors., Journal for Immunotherapy of Cancer, vol. 10, No. Suppl 2,Nov. 1, 2022 (Nov. 1, 2022), p. A… [cited by applicant]
Seamen et al., Eradication of Tumors through Simultaneous Ablation of CD276/B7-H3-Positive Tumor Cells and Tumor Vasculature., Cancer Cell 31, 501-515, Apr. 10, 2017. [cited by applicant]
Skokos et al., A class of costimulatory CD28-bispecific antibodies that enhance the antitumor activity of CD3-bispecific antibodies., Sci Transl Med. Jan. 8, 2020;12(525):eaaw7888. doi: 10.1126/scitranslmed.aaw7888. [cited by applicant]
Steffen Dickopf et al, “Format and geometries matter: Structure-based design defines the functionality of bispecific antibodies”, [cited by applicant]
Roda-Navarro Pedro et al, “Understanding the Spatial Topology of Artificial Immunological Synapses Assembled in T Cell-Redirecting Strategies: A Major Issue in Cancer Immunotherapy”, Frontiers in Cell and Developmental … [cited by applicant]
Suurs Frans V et al, “A review of bispecific antibodies and antibody constructs in oncology and clinical challenges”, Apr. 24, 2019 (Apr. 24, 2019), vol. 201, p. 103-119. [cited by applicant]
Chen Shixue et al, “Immunoglobulin Gamma-Like Therapeutic Bispecific Antibody Formats for Tumor Therapy”, US Feb. 11, 2019 (Feb. 11, 2019), vol. 2019, p. 1-13. [cited by applicant]
Van Blarcom, Thomas et al, “Productive common light chain libraries yield diverse panels of high affinity bispecific antibodies”, MABS,vol. 10, No. 2, Dec. 14, 2017 (Dec. 14, 2017), p. 256-268. [cited by applicant]
Hedvat Michael et al, “697?Tumor-targeted CD28 costimulatory bispecific antibodies enhance T cell activation in solid tumors”, Journal for Immunotherapy of Cancer,vol. 8, No. Suppl 3, Nov. 1, 2020 (Nov. 1, 2020), p. A73… [cited by applicant]
Liu et al., Tumor-targeted CD28 bispecific POWERbody for safe and synergistic T cell-mediated immunotherapy., 2022 AACR Annual Meeting, Abstract No. 2888 (poster). [cited by applicant]
Liu et al., Abstract 2888: Tumor-targeted CD28 bispecific POWERbody for safe and synergistic T cell-mediated immunotherapy., Cancer Res (2022) 82 (12_Supplement): 2888. [cited by applicant]
Ahmed et al., Humanized Affinity-matured Monoclonal Antibody 8H9 Has Potent Antitumor Activity and Binds to FG Loop of Tumor Antigen B7-H3*., The Journal of Biological Chemistry vol. 290, No. 50, pp. 30018-30029, Dec. 1… [cited by applicant]
Bohlen et al., Cytolysis of Leukemic B-Cells by T-Cells Activated via Two Bispecific Antibodies., Cancer Research 53, 4310-4314, Sep. 15, 1993. [cited by applicant]
Correnti et al., Simultaneous multiple interaction T-cell engaging (SMITE) bispecific antibodies overcome bispecific T-cell engager (BiTE) resistance via CD28 co-stimulation., Leukemia (2018) 32:1239-1243. [cited by applicant]
Hodge et al., Induction of Antitumor Immunity by Recombinant Vaccinia Viruses Expressing B7-1 or B7-2 Costimulatory Molecules., Cancer Research 54, 5552-5555, Nov. 1, 1994. [cited by applicant]
Hui et al., T cell costimulatory receptor CD28 is a primary target for PD-1-mediated inhibition., Science 10.1126/science.aaf1292, Mar. 9, 2017. [cited by applicant]
Jansen et al., An intra-tumoral niche maintains and differentiates stem-like CD8 T cells., Nature vol. 576, pp. 465-470 (2019). [cited by applicant]
Kamphorst et al., Rescue of exhausted CD8 T cells by PD-1-targeted therapies is CD28-dependent., Science 10.1126/science.aaf0683, Mar. 9, 2017. [cited by applicant]
Loo et al., Development of an Fc-Enhanced Anti-B7-H3 Monoclonal Antibody with Potent Antitumor Activity., Clin Cancer Res; 18(14) Jul. 15, 2012. [cited by applicant]
Mary et al., Antagonist properties of monoclonal antibodies targeting human CD28: role of valency and the heavy-chain constant domain., MAbs. Jan.-Feb. 2013;5(1):47-55. doi: 10.4161/mabs.22697. Epub Dec. 5, 2012. [cited by applicant]
Poirier et al., Advantages of Papio anubis for preclinical testing of immunotoxicity of candidate therapeutic antagonist antibodies targeting CD28., mAbs, 6:3, 697-706, DOI: 10.4161/mabs.28375. [cited by applicant]
Poirier et al., First-in-Human Study in Healthy Subjects with FR104, a Pegylated Monoclonal Antibody Fragment Antagonist of CD28., J Immunol. Dec. 15, 2016;197(12):4593-4602. doi: 10.4049/jimmunol.1601538. Epub Nov. 14,… [cited by applicant]
Seaman et al., Genes that Distinguish Physiological and Pathological Angiogenesis., Cancer Cell. Jun. 2007; 11(6):539-54. doi: 10.1016/j.ccr.2007.04.017. [cited by applicant]
Shiao et al., Immunomodulatory Properties of FK734, a Humanized Anti-CD28 Monoclonal Antibody With Agonistic and Antagonistic Activities., Transplantation. Feb. 15, 2007;83(3):304-13. doi: 10.1097/01.tp.0000251426.46312… [cited by applicant]
Moore et al., A robust heterodimeric Fc platform engineered for efficient development of bispecific antibodies of multiple formats., Methods. Feb. 1, 2019;154:38-50. doi:10.1016/j.ymeth.2018.10.006. Epub Oct. 23, 2018. [cited by applicant]
Moore, Gregory et al., PDLI-targeted CD28 costimulatory bispecific antibodies enhance T cell activation in solid tumors., Jul. 1, 2021 (Jul. 1, 2021), XP055881523, Retrieved from the Internet: URL:https://investors.xenc… [cited by applicant]
Marchalonis et al., The antibody repertoire in evolution: chance, selection, and continuity., Dev Comp Immunol. 2006;30(1-2):223-47. doi: 10.1016/j.dci.2005.06.011. [cited by applicant]
Lippow et al., Computational design of antibody-affinity improvement beyond in vivo maturation., Nat Biotechnol. Oct. 2007;25(10):1171-6. doi: 10.1038/nbt1336. Epub Sep. 23, 2007. [cited by applicant]
Altshuler et al., Generation of Recombinant Antibodies and Means for Increasing Their Affinity., Biochemistry (Moscow), 75(13):1584-1605 (2010). [cited by applicant]
Vajda et al., Progress toward improved understanding of antibody maturation., Current Opinion in Structural Biology, 67 pp. 226-231 (2021). [cited by applicant]
Marks et al., How repertoire data are changing antibody science., J Biol Chem. Jul. 17, 2020;295(29):9823-9837. doi: 10.1074/jbc.REV120.010181. [cited by applicant]
Akbar et al., A compact vocabulary of paratope-epitope interactions enables predictability of antibody-antigen binding., Cell Rep. Mar. 16, 2021;34(11):108856. doi: 10.1016/j.celrep.2021.108856. [cited by applicant]
Lo et al., Conformational epitope matching and prediction based on protein surface spiral features., BMC Genomics 2021, 22(Suppl 2): 116. https://doi.org/10.1186/s12864-020-07303-5. [cited by applicant]
David E Szymkowski et al: “Creating the next generation of protein therapeutics through rational drug design”, Current Opinion in Drug Discovery & Development, Sep. 1, 2005 (Sep. 1, 2005), England, pp. 590, XP055354917,… [cited by applicant]
Tang Y et al: “Selection of linkers for a catalytic single-chain antibody using phage display technology”, Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, US, vol. 271, No. 26, … [cited by applicant]
Cuesta et al., Multivalent antibodies: when design surpasses evolution., Trends Biotechnol. Jul. 2010;28(7):355-62. doi: 10.1016/j.tibtech.2010.03.007. Epub May 4, 2010. [cited by applicant]
Mertens, Nico, Tribodies: Fab-scFv Fusion Proteins as a Platform to Create Multifunctional Pharmaceuticals., In: “Bispecific Antibodies”, Jan. 1, 2011 (Jan. 1, 2011), Springer Berlin Heidelberg, Berlin, Heidelberg, XP05… [cited by applicant]
Jin Yixin et al.: “Development of STEAP1 targeting chimeric antigen receptor foradoptive cell therapy against cancer”, Molecular Therapy—Oncolytics, [Online] vol. 26, Sep. 15, 2022 (Sep. 15, 2022), pp. 189-206. [cited by applicant]
Bhatia Vipul et al: “Targeting advanced prostate cancer with STEAP1 chimeric antigen receptor T cell therapy”, bioRxiv, May 17, 2022 (May 17, 2022), pp. 1-47, XP093203200. [cited by applicant]
Dragovich Matthew A. et al: “Abstract 2983: Tumor-specific CD28 costimulatory bispecific antibodies enhance T cell activation in solid tumors”, Cancer Research, vol. 83, No. 7_Supplement, Apr. 4, 2023 (Apr. 4, 2023), pp… [cited by applicant]
Warwas Karsten M. et al: “Co-Stimulatory Bispecific Antibodies Induce Enhanced T Cell Activation and Tumor Cell Killing in Breast Cancer Models”, Frontiers in Immunology, vol. 12, Aug. 16, 2021 (Aug. 16, 2021), XP093070… [cited by applicant]
Brandl Martina et al.: “Bispecific antibody fragments with CD20 x CD28 specificity allow effective autologous and allogeneic T-cell activation against malignant cells in peripheral blood and bone marrow cultures from pa… [cited by applicant]
Otz, T., Große-Hovest, L., Hofmann, M et al. A bispecific single-chain antibody that mediates target cell-restricted, supra-agonistic CD28 stimulation and killing of lymphoma cells. Leukemia 23, 71-77 (2009). https://do… [cited by applicant]