Granted Patent
B2
US 12,187,763 · App. 17/173,767 · Granted Jan 7, 2025
Chromatography resin and uses thereof
Assignee:
ImmunityBio, Inc.
C07K1/22B01D15/3809B01D61/027B01D61/145B01D61/58C07K14/5443C07K14/7155C07K14/745C07K16/36B01D2315/16C07K2317/565C07K2319/00
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Abstract
An affinity chromatography resin comprising an anti-tissue factor antibody or antigen-binding fragment thereof attached to a base resin, and methods of using the same.
Claims (70)
1. A method of purifying a multi-chain chimeric polypeptide, the method comprising:
loading an affinity chromatography resin with a liquid comprising the multi-chain chimeric polypeptide;
washing the affinity chromatography resin using one or more wash buffer(s); and
eluting the multi-chain chimeric polypeptide using an elution buffer, wherein:
the affinity chromatography resin comprises an anti-tissue factor antibody or antigen-binding fragment thereof comprising a heavy chain variable domain comprising a CDR1 of SEQ ID NO: 1, a CDR2 of SEQ ID NO: 2 or 9, and a CDR3 of SEQ ID NO: 3, and a light chain variable domain comprising a CDR1 of SEQ ID NO: 4, a CDR2 of SEQ ID NO: 5, and a CDR3 of SEQ ID NO: 6, attached to a base resin;
the multi-chain chimeric polypeptide comprises:
(a) a first chimeric polypeptide comprising:
(i) a first target-binding domain comprising a sequence that is at least 80% identical to amino acids 19 to 305 of SEQ ID NO: 70;
(ii) a soluble tissue factor domain comprising a sequence that is at least 80% identical to SEQ ID NO: 10; and
(iii) a first domain of a pair of affinity domains comprising a sequence that is at least 80% identical to SEQ ID NO: 125; and
(b) a second chimeric polypeptide comprising:
(i) a second domain of a pair of affinity domains comprising a sequence that is at least 80% identical to SEQ ID NO: 123; and
(ii) a second target-binding domain comprising a sequence that is at least 80% identical to amino acids 19 to 305 of SEQ ID NO: 70;
the first chimeric polypeptide and the second chimeric polypeptide associate through the binding of the first domain and the second domain of the pair of affinity domains; and
the multi-chain chimeric polypeptide does not stimulate blood coagulation in a mammal.
2. The method of claim 1 , wherein the liquid comprising the multi-chain chimeric polypeptide is a clarified liquid culture medium.
3. The method of claim 1 , wherein the liquid comprising the multi-chain chimeric polypeptide comprises a cell lysate.
4. The method of claim 1 , wherein the one or more wash buffer(s) are:
(i) a first wash buffer comprising phosphate buffered saline; and
(ii) a second wash buffer comprising 0.01 M to 0.2 M citrate and having a pH of 4.5 to 5.5.
5. The method of claim 4 , wherein:
(i) the first wash buffer is phosphate buffered saline; and
(ii) the second wash buffer is 0.1 M citrate, pH 5.0.
6. The method of claim 1 , wherein the elution buffer comprises 0.01 M to 0.2 M acetate and has a pH of 2.5 to 3.5.
7. The method of claim 6 , wherein the elution buffer comprises 0.1 M acetate and has a pH of 2.9.
8. The method of claim 1 , wherein the method further comprises:
performing one or more additional unit operations on an eluate obtained from the step of eluting the multi-chain chimeric polypeptide.
9. The method of claim 8 , wherein the one or more additional unit operations comprises, in sequential order:
performing low pH viral inactivation;
performing depth filtration;
performing polishing chromatography;
performing nanofiltration; and
performing ultrafiltration and diafiltration (UF/DF).
10. The method of claim 1 , wherein the heavy chain variable domain comprises a sequence that is at least 90% identical to SEQ ID NO: 7, and the light chain variable domain comprises a sequence that is at least 90% identical to SEQ ID NO: 8.
11. The method of claim 10 , wherein the heavy chain variable domain comprises SEQ ID NO: 7, and the light chain variable domain comprises SEQ ID NO: 8.
12. The method of claim 1 , wherein the base resin is sepharose.
13. The method of claim 1 , wherein the base resin is any support material.
14. The method of claim 13 , wherein the support material is agarose or a capto resin.
15. The method of claim 1 , wherein the anti-tissue factor antibody or antigen-binding fragment thereof is non-covalently attached to the base resin.
16. The method of claim 1 , wherein the anti-tissue factor antibody or antigen-binding fragment thereof is covalently attached to the base resin.
17. The method of claim 16 , wherein the anti-tissue factor antibody or antigen-binding fragment thereof is covalently attached to the base resin through the formation of a disulfide bond between a cysteine in the anti-tissue factor antibody or antigen-binding fragment thereof and a chemical group on the base resin.
18. The method of claim 16 , wherein the anti-tissue factor antibody or antigen-binding fragment thereof is covalently attached to the base resin through the formation of a covalent bond between a free amine of the anti-tissue factor antibody or antigen-binding domain and a chemical group on the base resin.
19. The method of claim 18 , wherein the base resin is CNBr-activated or N-hydroxysuccinimide (NHS)-activated solid support material.
20. The method of claim 18 , wherein the covalent bond is represented by Formula I below:
wherein R represents the anti-tissue factor antibody or antigen-binding fragment thereof.
21. The method of claim 1 , wherein the first target-binding domain and the soluble tissue factor domain directly abut each other in the first chimeric polypeptide.
22. The method of claim 1 , wherein the first chimeric polypeptide further comprises a linker sequence between the first target-binding domain and the soluble tissue factor domain in the first chimeric polypeptide.
23. The method of claim 1 , wherein the soluble tissue factor domain and the first domain of the pair of affinity domains directly abut each other in the first chimeric polypeptide.
24. The method of claim 1 , wherein the first chimeric polypeptide further comprises a linker sequence between the soluble tissue factor domain and the first domain of the pair of affinity domains in the first chimeric polypeptide.
25. The method of claim 1 , wherein the second domain of the pair of affinity domains and the second target-binding domain directly abut each other in the second chimeric polypeptide.
26. The method of claim 1 , wherein the second chimeric polypeptide further comprises a linker sequence between the second domain of the pair of affinity domains and the second target-binding domain in the second chimeric polypeptide.
27. The method of claim 1 , wherein the soluble tissue factor domain is a soluble human tissue factor domain.
28. The method of claim 1 , wherein:
the first target-binding domain comprises a sequence that is at least 90% identical to amino acids 19 to 305 of SEQ ID NO: 70;
the soluble tissue factor domain comprises a sequence that is at least 90% identical to SEQ ID NO: 10;
the first domain of the pair of affinity domains comprises a sequence that is at least 90% identical to SEQ ID NO: 125;
the second target-binding domain comprises a sequence that is at least 90% identical to amino acids 19 to 305 of SEQ ID NO: 70; and
the second domain of the pair of affinity domains comprises a sequence that is at least 90% identical to SEQ ID NO: 123.
29. The method of claim 28 , wherein:
the first target-binding domain comprises a sequence that is at least 95% identical to amino acids 19 to 305 of SEQ ID NO: 70;
the soluble tissue factor domain comprises a sequence that is at least 95% identical to SEQ ID NO: 10;
the first domain of the pair of affinity domains comprises a sequence that is at least 95% identical to SEQ ID NO: 125;
the second target-binding domain comprises a sequence that is at least 95% identical to amino acids 19 to 305 of SEQ ID NO: 70; and
the second domain of the pair of affinity domains comprises a sequence that is at least 95% identical to SEQ ID NO: 123.
30. The method of claim 29 , wherein:
the first target-binding domain comprises a sequence of amino acids 19 to 305 of SEQ ID NO: 70;
the soluble tissue factor domain comprises SEQ ID NO: 10;
the first domain of the pair of affinity domains comprises SEQ ID NO: 125;
the second target-binding domain comprises a sequence of amino acids 19 to 305 of SEQ ID NO: 70; and
the second domain of the pair of affinity domains comprises SEQ ID NO: 123.
Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Jul 17, 2024
From: HCW BIOLOGICS INC.
To: IMMUNITYBIO, INC.
Reel/Frame 068014/0474 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Mar 16, 2021
From: WONG, HING C.; JIAO, JIN-AN; PRENDES, CAITLIN
To: HCW BIOLOGICS, INC.
Reel/Frame 055600/0489 →
Continuity (3)
Provisional Application
62982002
· Feb 26, 2020
Provisional Application
62975141
· Feb 11, 2020
References Cited (400)
US 6117980A
· Gonzalez et al.
· 2000
[cited by applicant]
US 7452537B2
· Bauer et al.
· 2008
[cited by applicant]
US 7482436B2
· Sugimura et al.
· 2009
[cited by applicant]
US 7488802B2
· Collins et al.
· 2009
[cited by applicant]
US 7521051B2
· Collins et al.
· 2009
[cited by applicant]
US 7612181B2
· Wu et al.
· 2009
[cited by applicant]
US 7691380B2
· Thorpe et al.
· 2010
[cited by applicant]
US 7723482B2
· Soulillou et al.
· 2010
[cited by applicant]
US 7968094B2
· Jiao
· 2011
[cited by examiner]
US 8007795B2
· Jiao et al.
· 2011
[cited by applicant]
US 8133485B2
· Levi-Schaffer et al.
· 2012
[cited by applicant]
US 8217149B2
· Irving et al.
· 2012
[cited by applicant]
US 8258268B2
· Wu et al.
· 2012
[cited by applicant]
US 8475792B2
· Dall'Acqua et al.
· 2013
[cited by applicant]
US 8552156B2
· Takayanagi et al.
· 2013
[cited by applicant]
US 8586714B2
· Ghayur et al.
· 2013
[cited by applicant]
US 8716450B2
· Ghayur et al.
· 2014
[cited by applicant]
US 8722855B2
· Ghayur et al.
· 2014
[cited by applicant]
US 8735546B2
· Ghayur et al.
· 2014
[cited by applicant]
US 8741604B2
· Campbell et al.
· 2014
[cited by applicant]
US 8753640B2
· Wu et al.
· 2014
[cited by applicant]
US 8759494B2
· Bachmann et al.
· 2014
[cited by applicant]
US 8822645B2
· Ghayur et al.
· 2014
[cited by applicant]
US 9035026B2
· Hoffmann et al.
· 2015
[cited by applicant]
US 9067997B2
· Romagne et al.
· 2015
[cited by applicant]
US 9085623B2
· Rother et al.
· 2015
[cited by applicant]
US 9090684B2
· Borras et al.
· 2015
[cited by applicant]
US 9226962B2
· Le Gall et al.
· 2016
[cited by applicant]
US 9238084B2
· Liu et al.
· 2016
[cited by applicant]
US 9273136B2
· Rader et al.
· 2016
[cited by applicant]
US 9371395B2
· Takahashi et al.
· 2016
[cited by applicant]
US 9441034B2
· Sivakumar et al.
· 2016
[cited by applicant]
US 9505843B2
· Kim et al.
· 2016
[cited by applicant]
US 9617345B2
· Berne et al.
· 2017
[cited by applicant]
US 9701758B2
· Cooper et al.
· 2017
[cited by applicant]
US 20010044427A1
· Mazel et al.
· 2001
[cited by applicant]
US 20060159655A1
· Collins et al.
· 2006
[cited by applicant]
US 20070160579A1
· Schmitz et al.
· 2007
[cited by applicant]
US 20120171197A1
· Eriksson et al.
· 2012
[cited by applicant]
US 20120264920A1
· Wang
· 2012
[cited by examiner]
US 20140242077A1
· Choi
· 2014
[cited by applicant]
US 20150259429A1
· Benaroch et al.
· 2015
[cited by applicant]
US 20160175397A1
· Umana et al.
· 2016
[cited by applicant]
US 20170198042A1
· Williams et al.
· 2017
[cited by applicant]
US 20180200366A1
· Wong
· 2018
[cited by applicant]
US 20200123607A1
· Serrano Marugan et al.
· 2020
[cited by applicant]
US 20210061897A1
· Ledbetter et al.
· 2021
[cited by applicant]
US 20230372399A1
· Wong
· 2023
[cited by applicant]
US 20230398151A1
· Wong
· 2023
[cited by applicant]
US 20240124543A1
· Wong
· 2024
[cited by applicant]
US 20240124544A1
· Wong
· 2024
[cited by applicant]
US 20240132561A1
· Wong
· 2024
[cited by applicant]
CN 1844150
· 2006
[cited by applicant]
CN 101653603
· 2010
[cited by applicant]
CN 101965364
· 2011
[cited by applicant]
CN 102153653
· 2011
[cited by applicant]
CN 106255703
· 2016
[cited by applicant]
CN 109513003
· 2019
[cited by applicant]
EP 1245676
· 2002
[cited by applicant]
EP 1719528
· 2006
[cited by applicant]
EP 2537933
· 2012
[cited by applicant]
EP 3029069
· 2016
[cited by applicant]
EP 3348276
· 2018
[cited by applicant]
JP 2005124568
· 2005
[cited by applicant]
JP 2008536487
· 2008
[cited by applicant]
JP 2009512433
· 2009
[cited by applicant]
JP 4361133
· 2009
[cited by applicant]
KR 20160127688
· 2016
[cited by applicant]
KR 101778439
· 2017
[cited by applicant]
WO WO1995015341
· 1995
[cited by applicant]
WO WO1996001653
· 1996
[cited by applicant]
WO WO2001083755
· 2001
[cited by applicant]
WO WO2002083152
· 2002
[cited by applicant]
WO WO2003037911
· 2003
[cited by applicant]
WO WO2003104425
· 2003
[cited by applicant]
WO WO2004076488
· 2004
[cited by applicant]
WO WO2006096828
· 2006
[cited by applicant]
WO WO2006097743
· 2006
[cited by applicant]
WO WO2006119897
· 2006
[cited by applicant]
WO WO2008096158
· 2008
[cited by applicant]
WO WO2011127324
· 2011
[cited by applicant]
WO WO2012040323
· 2012
[cited by applicant]
WO WO2012120125
· 2012
[cited by applicant]
WO WO2012170470
· 2012
[cited by applicant]
WO WO2012175222
· 2012
[cited by applicant]
WO WO2012175692
· 2012
[cited by applicant]
WO WO2013068946
· 2013
[cited by applicant]
WO WO2014007513
· 2014
[cited by applicant]
WO WO2014026054
· 2014
[cited by applicant]
WO WO2014095808
· 2014
[cited by applicant]
WO WO2014130635
· 2014
[cited by applicant]
WO WO2014159531
· 2014
[cited by applicant]
WO WO2015089881
· 2015
[cited by applicant]
WO WO2016106221
· 2016
[cited by applicant]
WO WO2016154585
· 2016
[cited by applicant]
WO WO2016166348
· 2016
[cited by applicant]
WO WO2017053748
· 2017
[cited by applicant]
WO WO2017083612
· 2017
[cited by applicant]
WO WO2017149538
· 2017
[cited by applicant]
WO WO2017189526
· 2017
[cited by applicant]
WO WO2018067825
· 2018
[cited by applicant]
WO WO2018075989
· 2018
[cited by applicant]
WO WO2018129007
· 2018
[cited by applicant]
WO WO2018158350
· 2018
[cited by applicant]
WO WO2018183169
· 2018
[cited by applicant]
WO WO2018165208
· 2018
[cited by applicant]
WO WO2019046313
· 2019
[cited by applicant]
WO WO2020047299
· 2020
[cited by applicant]
WO WO2020047333
· 2020
[cited by applicant]
WO WO2020047462
· 2020
[cited by applicant]
WO WO2020047473
· 2020
[cited by applicant]
WO WO2021163369
· 2021
[cited by applicant]
Guha et al., Affinity purification of human tissue factor: Interaction of factor VII and tissue factor in detergent micelles, 1986, Biochemistry, vol. 83, pp. 299-302 (Year: 1986).
[cited by examiner]
Urh et al., Affinity Chromotography: General Methods, 2009, Methods in Enzymology, vol. 463 (Year: 2009).
[cited by examiner]
G-Biosciences, The Basics of Affinity Purification/Affinity Chromatography, 2018, pp. 1-4 (Year: 2018).
[cited by examiner]
Helie et al., Application of the Protein Maker as a platform purification system for therapeutic antibody research and development, 2016, Computational and Structural Biotechnology Journal, vol. 14, pp. 238-244 (Year: 2…
[cited by examiner]
Bramer et al., Membrane Adsorber for the Fast Purification of a Monoclonal Antibody Using Protein A Chromatography, 2019, Membranes, vol. 9, Issue 159, pp. 1-15 (Year: 2019).
[cited by examiner]
Amersham Pharmacia Biotech, CNBr-activated Sepharose 4 Fast Flow, 1999, Affinity Chromatography, pp. 1-4 (Year: 1999).
[cited by examiner]
ThermoFisher, Covalent Immobilization of Affinity Ligands, 2018, pp. 1-22, retrieved from: https://www.thermofisher.com/us/en/home/life-science/protein-biology/protein-biology-learning-center/protein-biology-resource-li…
[cited by examiner]
Abbott et al., “Genomic organization, exact localization, and tissue expression of the human CD26 (dipeptidyl peptidase IV) gene,” Immunogenetics, Sep. 1994, 40(5):331-338.
[cited by applicant]
Abdul-Aziz et al., “Acute myeloid leukemia induces protumoral p16INK4a-driven senescence in the bone marrow microenvironment,” Blood, Jan. 31, 2019, 133(5):446-456.
[cited by applicant]
Aertgeerts et al., “Crystal structure of human dipeptidyl peptidase IV in complex with a decapeptide reveals details on substrate specificity and tetrahedral intermediate formation,” Protein Science, Feb. 2004, 13(2):41…
[cited by applicant]
Ait-Oufella el al., “Natural regulatory T cells control the development of atherosclerosis in mice,” Nature Medicine, Feb. 5, 2006, 12:178-180.
[cited by applicant]
Akbari, et al., “Design, expression and evaluation of a novel humanized single chain antibody against epidermal growth factor receptor (EGFR),” Protein Expr. Purif., 2016, 127:8-15.
[cited by applicant]
Ali et al., “Regulatory T cells in skin,” Immunology, Jul. 12, 2017, 152(3):372-381.
[cited by applicant]
Angevin et al., “First-in-human phase 1 of YS110, a monoclonal antibody directed against CD26 in advanced CD26-expressing cancers,” British Journal of Cancer, Mar. 14, 2017, 116(9):1126-1134.
[cited by applicant]
Bachelet et al., “Mast Cell Costimulation by CD226/CD112 (DNAM-1/Nectin-2) A Novel Interface in the Allergic Process,” Journal of Biological Chemistry, Sep. 15, 2006, 281(37):27190-6.
[cited by applicant]
Baker, et al., “Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders,” Nature, 2011, 479(7372): 232-236.
[cited by applicant]
Bennett et al., “Erratum: Killing the old: cell senescence in atherosclerosis,” Nature Reviews Cardiology, Jan. 12, 2017, 14(3):132.
[cited by applicant]
Bennett et al., “Killing the old: cell senescence in atherosclerosis,” Nature Reviews Cardiology, Dec. 12, 2016, 14(1):8-9, 2 pages.
[cited by applicant]
Bentebibel et al., “A First-in-Human Study and Biomarker Analysis of NKTR-214, a Novel IL2Raf Biased Cytokine, in Patients with Advanced or Metastatic Solid Tumors,” Cancer Discovery, Jun. 2019, 9(6):711-721.
[cited by applicant]
Bhat et al., “Astrocyte Senescence as a Component of Alzheimer's Disease,” PLoS One, Sep. 12, 2012, 7(9):e45069, 10 pages.
[cited by applicant]
Biran et al., “Senescent cells communicate via intercellular protein transfer,” Genes & Development, Apr. 8, 2015, 29(8):791-802, 13 pages.
[cited by applicant]
Borea et al., “Pharmacology of Adenosine Receptors: The State of the Art,” Physiological Reviews, May 31, 2918, 98(3):1591-1625.
[cited by applicant]
Borgerding et al., “B-lymphoma cells escape rituximab-triggered elimination by NK cells through increased HLA class I expression,” Experimental Hematology, Mar. 1, 2010, 38(3):213-21.
[cited by applicant]
Bork, “Powers and Pitfalls in Sequence Analysis: The 70% Hurdle,” Genome Research, 2000, 10:398-400.
[cited by applicant]
Bourgeois et al., “Regulation of cellular senescence via the FOXO4-p53 axis,” FEBS Lett., 2018, 592(12): 2083-2097.
[cited by applicant]
Bowie et al., “Deciphering the Message in Protein Sequences: Tolerance to Amino Acid Substitutions,” Science, 1990, 247:1306-1310.
[cited by applicant]
Boyman et al., “IL-7/Anti-IL-7 mAb Complexes Restore T Cell Development and Induce Homeostatic T Cell Expansion without Lymphopenia,” The Journal of Immunology, Jun. 1, 2008, 180:7265-7275.
[cited by applicant]
Boyman et al., “Selective Stimulation of T Cell Subsets with Antibody-Cytokine Immune Complexes,” Science, Mar. 31, 2006, 311(5769):1924-1927.
[cited by applicant]
Brennan et al., “Structural determination of lipid antigens captured at the CD1d-T-cell receptor interface,” PNAS, 2017, 114(31):8348-8353.
[cited by applicant]
Brighton et al., “Clearance of senescent decidual cells by uterine natural killer cells in cycling human endometrium,” Elife, Dec. 11, 2017, 6:e31274, 23 pages.
[cited by applicant]
Brooks et al., “Combined inhibition of PD1 and CD96 checkpoints improves survival in a resectable murine model of pancreatic cancer,” European Journal of Cancer, Jul. 1, 2016, 61:S189, 1 page.
[cited by applicant]
Broxmeyer et al., “Modulation of Hematopoietic Chemokine Effects In Vitro and In Vivo by DPP-4/CD26,” Stem Cells and Development, Mar. 4, 2016, 25(8):575-585.
[cited by applicant]
Brunstein et al., “Infusion of Ex Vivo Expanded T Regulatory Cells in Adults Transplanted with Umbilical Cord Blood: Safety Profile and Detection Kinetics,” Blood, Jan. 20, 2011, 117(3):1061-1070.
[cited by applicant]
Brunstein et al., “Umbilical cord blood-derived T regulatory cells to prevent GVHD:kinetics, toxicity profile, and clinical effect,” Blood, Feb. 25, 2016, 127(8):1044-1051.
[cited by applicant]
Buhling et al., “Functional role of CD26 on human B lymphocytes,” Immunology Letters, Feb. 1995, 45(1-2):47-51.
[cited by applicant]
Burgess et al., “Possible Dissociation of the Heparin-binding and Mitogenic Activities of Heparin-binding (Acidic Fibroblast) GrowthFactor-1 from Its Receptor-binding Activities by Site-directed Mutagenesis of a Single …
[cited by applicant]
Bussian et al., “Clearance of senescent glial cells prevents tau-dependent pathology and cognitive decline,” Nature, Sep. 19, 2018, 562(7728):578-582, 21 pages.
[cited by applicant]
Cai et al., “Chibby suppresses aerobic glycolysis and proliferation of nasopharyngeal carcinoma via the Wnt/β-catenin-Lin28/let7-PDK1 cascade,” Journal of Experimental & Clinical Cancer Research, Dec. 1, 2018, 37(1):104.
[cited by applicant]
Cao et al., “Expression and characterization of recombinant humanized anti-HER2 single-chain antibody in Pichia pastoris for targeted cancer therapy,” Biotechnology Letters, Jul. 1, 2015, 37(7):1347-54.
[cited by applicant]
Cao, “Self-regulation and cross-regulation of pattern-recognition receptor signaling in health and disease,” Nature Reviews Immunology, Dec. 29, 2015, 16(1):35-50.
[cited by applicant]
Carr et al., “NK Cell-Mediated Lysis of Autologous HCMV-Infected Skin Fibroblasts Is Highly Variable among NK Cell Clones and Polyclonal NK Cell Lines,” Clinical Immunology, Nov. 2002, 105(2):126-140.
[cited by applicant]
Catania et al., “The tumor-targeting immunocytokine F16-IL2 in combination with doxorubicin: dose escalation in patients with advanced solid tumors and expansion into patients with metastatic breast cancer,” Cell Adhesi…
[cited by applicant]
Cavinato et al., “Molecular mechanisms of UVB-induced senescence of dermal fibroblasts and its relevance for photoaging of the human skin,” Experimental Gerontology. Aug. 2017, 94:78-82.
[cited by applicant]
Chalan et al., “Expression of Lectin-Like Transcript 1, the Ligand for CD161, in Rheumatoid Arthritis,” PLoS One, 2015, 10(7):e0132436.
[cited by applicant]
Chambers et al., “Can blocking inflammation enhance immunity during aging?,” Journal of Allergy and Clinical Immunology, May 2020, 145(5):1323-1331.
[cited by applicant]
Chance et al., “A simple and rapid assay of oxidative phosphorylation,” Nature, Jun. 1955, 175(4469):1120-1121.
[cited by applicant]
Chattopadyhay et al., “Structural Basis of Inducible Costimulator Ligand Costimulatory Function: Determination of the Cell Surface Oligomeric State and Functional Mapping of the Receptor Binding Site of the Protein1,” J…
[cited by applicant]
Chen et al., “Sterile inflammation: sensing and reacting to damage,” Nature Reviews Immunology, Nov. 19, 2010, 10(12):826-837.
[cited by applicant]
Chichili et al., “Linkers in the structural biology of protein-protein interactions,” Protein Science, Feb. 2013, 22(2):153-67.
[cited by applicant]
Childs et al., “Senescent cells: an emerging target for diseases of ageing,” Nature Reviews Drug Discovery, Jul. 21, 2017, 16(10):718-735, 18 pages.
[cited by applicant]
Childs et al., “Senescent intimal foam cells are deleterious at all stages of atherosclerosis,” Science, Oct. 28, 2016, 354(6311):472-477.
[cited by applicant]
Chinta, et al., “Cellular senescence is induced by the environmental neurotoxin paraquat and bontributes to neuropathology linked to Parkinson's Disease,” Cell Rep., 2018, 22(4): 930-940.
[cited by applicant]
Chong et al., “CD36 initiates the secretory phenotype during the establishment of cellular senescence,” EMBO Rep., May 18, 2018, 19(6):e45274, 13 pages.
[cited by applicant]
Ciaglia, et al., “Recognition by natural killer cells of N6-isopentenyladensoine-treated human glioma cell lines,” Int. J. Cancer, 2018 142(1): 176-190.
[cited by applicant]
Cichocki et al., “GSK3 inhibition drives maturation of NK cells and enhances their antitumor activity,” Cancer Research, Oct. 15, 2017, 77(20):5664-75.
[cited by applicant]
Cifaldi et al., “Boosting Natural Killer Cell-Based Immunotherapy with Anticancer Drugs: a Perspective,” Trends Molecular Medicine, Dec. 2017, 23(12):1156-1175, 20 pages.
[cited by applicant]
Cipriani et al., “Hippocampal Radial Glial Subtypes and Their Neurogenic Potential in Human Fetuses and Healthy and Alzheimer's Disease Adults,” Cerebral Cortex, May 2, 2018, 28(7):2458-2478, 21 pages.
[cited by applicant]
Clayton et al., “Soluble T Cell Immunoglobulin Mucin Domain 3 Is Shed from CD8 T Cells by the Sheddase ADAM10, Is Increased in Plasma during Untreated HIV Infection, and Correlates with HIV Disease Progression,” J Viral…
[cited by applicant]
Collado et al., “Senescence in tumours: evidence from mice and humans,” Nature Reviews Cancer, Jan. 2010, 10(1):51-57.
[cited by applicant]
Conarello et al., “Mice lacking dipeptidyl peptidase IV are protected against obesity and insulin resistance,” Proc. Natl. Acad. Sci. U.S.A., May 27, 2003, 100(11):6825-6830.
[cited by applicant]
Conlon et al., “Abstract CT082: Phase (Ph) I/Ib study of NIZ985 with and without spartalizumab (PDR001) in patients (pts) with metastatic/unresectable solid tumors,” Cancer Res. 79(13 Suppl.):CT082, Jul. 1, 2019, 2 page…
[cited by applicant]
Coppe et al., “Tumor Suppressor and Aging Biomarker p16INK4a Induces Cellular Senescence without the Associated Inflammatory Secretory Phenotype,” Journal of Biological Chemistry, Oct. 21, 2011, 286(42): 36396-36403.
[cited by applicant]
Cosman et al., “ULBPs, novel MHC class I-related molecules, bind to CMV glycoprotein UL16 and stimulate NK cytotoxicity through the NKG2D receptor,” Immunity, Feb. 1, 2001, 14(2):123-33.
[cited by applicant]
Costa et al., “Targeting the epidermal growth factor receptor can counteract the inhibition of natural killer cell function exerted by colorectal tumor-associated fibroblasts,” Frontiers in Immunology, May 29, 2018, 9:1…
[cited by applicant]
Crews et al., “Molecular mechanisms of neurodegeneration in Alzheimer's disease,” Human Molecular Genetics, Apr. 22, 2010, 19(R1):R12-R20, 9 pages.
[cited by applicant]
Cromie et al., “Nanobodies and their use in GPCR drug discovery,” Current Topics in Medicinal Chemistry, Dec. 1, 2015, 15(24):2543-57.
[cited by applicant]
Czaja et al., “A comprehensive analysis of the binding of anti-KIR antibodies to activating KIRs,” Genes and Immunity, Jan. 2014, 15(1), 15 pages.
[cited by applicant]
Da Silva et al., “Dipeptidylpeptidase 4 inhibition enhances lymphocyte trafficking, improving both naturally occurring tumor immunity and immunotherapy,” Nature Immunology, Jun. 15, 2015, 16(8):850-858, 11 pages.
[cited by applicant]
Dall'Era et al., “Adoptive Regulatory T Cell Therapy in a Patient with Systemic Lupus Erythematosus,” Arthritis Rheumatology, Mar. 2019, 71(3):431-440.
[cited by applicant]
De Crescenzo et al., “Engineering TGF-β Traps: Artificially Dimerized Receptor Ectodomains as High-affinity Blockers of TGF-β Action,” Transforming Growth Factor-β in Cancer Therapy, vol. II, 2008, Humana Press, 671-84.
[cited by applicant]
De Genst et al., “Antibody repertoire development in camelids,” Developmental & Comparative Immunology, Jan. 1, 2006, 30(1-2):187-98.
[cited by applicant]
De Meyer et al., “Nanobody-based products as research and diagnostic tools,” Trends in Biotechnology, May 1, 2014, 32(5):263-70.
[cited by applicant]
De Stefano et al., “Establishing pathological cut-offs of brain atrophy rates in multiple sclerosis,” Journal of Neurology, Neurosurgery, and Psychiatry, Jan. 2016, 87(1):93-99.
[cited by applicant]
Deacon, “Physiology and Pharmacology of DPP-4 in Glucose Homeostasis and the Treatment of Type 2 Diabetes,” Frontiers in Endocrinology, Feb. 2019, 10:80, 14 pages.
[cited by applicant]
Deaglio et al., “Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression,” Journal of Experimental Medicine, May 14, 2007, 204(6):1257-1265.
[cited by applicant]
Demaria et al., “An Essential Role for Senescent Cellsin Optimal Wound Healing through Secretion of PDGF-AA,” Developmental Cell, Dec. 22, 2014, 31(6):722-733.
[cited by applicant]
Deyev et al., “Design of multivalent complexes using the barnase⋅ barstar module,” Nature Biotechnology, Dec. 2003, 21(12):1486-92.
[cited by applicant]
Di Ianni et al., “Tregs prevent GVHD and promote immune reconstitution inHLA-haploidentical transplantation,” Blood, Apr. 7, 2011, 117(14):3921-3928.
[cited by applicant]
Dietel et al., “Decreased numbers of regulatory T cells are associated with human atherosclerotic lesion vulnerability and inversely correlate with infiltrated mature dendritic cells,” Atherosclerosis, Sep. 2013, 230:92…
[cited by applicant]
DiGiammarino et al., “Design and generation of DVD-Ig™ molecules for dual-specific targeting,” Therapeutic Proteins: Methods and Protocols, Methods in Molecular Biology, 2012, Humana Press, Totowa, NJ., 899:145-516.
[cited by applicant]
Dikov et al., “New fluorescent method for the histochemical detection of tripeptidyl peptidase I using glycy1-1-prolyl-1-met-2-anthraquinonyl hydrazide as substrate,” Cellular and Molecular Biology, Jan. 1, 2004, 50 Onl…
[cited by applicant]
Dimri et al., “A biomarker that identifies senescent human cells in culture and in aging skin in vivo,” Proceedings of the National Academy of Sciences, Sep. 29, 1995, 92(20):9363-9367.
[cited by applicant]
Dinarello, “Interleukin 1 and interleukin 18 as mediators of inflammation and the aging process,” The American Journal of Clinical Nutrition, Feb. 1, 2006, 83(2):447S-455S.
[cited by applicant]
Docagne et al., “A soluble transforming growth factor-β (TGF-β) type I receptor mimics TGF-β responses,” Journal of Biological Chemistry, Dec. 7, 2001, 276(49):46243-50.
[cited by applicant]
Dong et al., “Characterization of adenosine deaminase binding to human CD26 on T cells and its biologic role in immune response,” Journal of Immunology, Feb. 15, 1996, 156(4):1349-1355.
[cited by applicant]
Dong et al., “Determination of adenosine deaminase binding domain on CD26 and its immunoregulatory effect on T cell activation,” Journal of Immunology, Dec. 15, 1997, 159(12):6070-6076.
[cited by applicant]
Dong et al., “Loss of methylation at the IFNG promoter and CNS-1 is associated with the development of functional IFN-γ memory in human CD4+T lymphocytes,” European Journal of Immunology, 2013, 43(3), 793-804.
[cited by applicant]
Dou et al., “Cytoplasmic chromatin triggers inflammation in senescence and cancer,” Nature, Oct. 4, 2017, 550(7676):402-406, 21 pages.
[cited by applicant]
Drees, et al., “Soluble production of a biologically active single-chain antibody against murine PD-L1 in
[cited by applicant]
Dubois et al., “Preassociation of IL-15 with IL-15Rα-IgG1-Fc Enhances Its Activity on Proliferation of NK and CD8+/CD44high T Cells and Its Antitumor Action,” The Journal of Immunology, Feb. 15, 2008, 180:2099-2106.
[cited by applicant]
Edwardraja et al., “Redesigning of anti-c-met single chain Fv antibody for the cytoplasmic folding and its structural analysis,” Biotechnology and Bioengineering, Jun. 15, 2010, 106(3):367-75.
[cited by applicant]
Eisenhut et al., “Ion Channels in Inflammation,” Pflugers Archive, Jan. 29, 2011, 461(4):401-421.
[cited by applicant]
Elgueta et al., “Molecular mechanism and function of CD40/CD40L engagement in the immune system,” Immunological Reviews, 2009, 229(1):152-172 doi.org/10.1111/j.1600-065X.2009.00782.x.
[cited by applicant]
Elpek et al., “Mature natural killer cells with phenotypic and functional alterations accumulate upon sustained stimulation with IL-15/IL-15Rα complexes,” Proceedings of the National Academy of Science, Dec. 14, 2010, 1…
[cited by applicant]
Engel et al., “The crystal structure of dipeptidyl peptidase IV (CD26) reveals its functional regulation and enzymatic mechanism,” Proc. Natl. Acad. Sci. U.S.A., Apr. 29, 2003, 100(9):5063-5068.
[cited by applicant]
Epardaud et al., “Interleukin-15/Interleukin-15RA Complexes Promote Destruction of Established Tumors by Reviving Tumor-Resident CD8+ T Cells,” Cancer Research 68: Apr. 15, 2008, 2972-2983.
[cited by applicant]
Esensten et al., “Regulatory T-cell therapy for autoimmune and autoinflammatory diseases: The next frontier,” The Journal of Allergy and Clinical Immunology, Dec. 1, 2018, 142(6):1710-1718.
[cited by applicant]
Farr, et al., “Targeting cellular senescence prevents age-related bone loss in mice,” Nat. Med., 2017, 23(9): 1072-1079.
[cited by applicant]
Fehniger et al., “A Phase 1 Trial of CNDO-109—Activated Natural Killer Cells in Patients with High-Risk Acute Myeloid Leukemia,” Biology of Blood and Marrow Transplantation, Aug. 2018, 24(8):1581-1589.
[cited by applicant]
Feng et al., “The yin and yang functions of extracellular ATP and adenosine in tumor immunity,” Cancer Cell International, Apr. 7, 2020, 20:110, 11 pages.
[cited by applicant]
Ferreira et al., “Next-generation regulatory T cell therapy,” Nature Reviews Drug Discovery, Sep. 20, 2019, 18(10):749-769, 21 pages.
[cited by applicant]
Ferrucci et al., “The origins of age-related proinflammatory state,” Blood, Mar. 15, 2005, 105(6):2294-2299.
[cited by applicant]
Finkelman et al., “Anti-cytokine antibodies as carrier proteins. Prolongation of in vivo effects of exogenous cytokines by injection of cytokine-anti-cytokine antibody complexes,” The Journal of Immunology, Aug. 1, 1993…
[cited by applicant]
Finkelstein et al., “Obesity and Severe Obesity Forecasts Through 2030,” American Journal of Preventative Medicine, Jun. 2012, 42(6):563-570.
[cited by applicant]
Ford et al., “TREM and TREM-like receptors in inflammation and disease,” Current Opinion in Immunology, Feb. 21, 2009, 21(1):38-46.
[cited by applicant]
Franceschi et al., “Inflamm-aging. An evolutionary perspective on immunosenescence,” Annals of the New York Academy of Sciences, Jun. 2000, 908:244-254.
[cited by applicant]
Frutoso et al., “Emergence of NK Cell Hyporesponsiveness after Two IL-15 Stimulation Cycles,” Journal of Immunology, May 30, 2018, 201: 493-506.
[cited by applicant]
Ganesh et al., “TGF-β Inhibition and Immunotherapy: Checkmate,” Immunity, Apr. 17, 2018, 48(4):626-628.
[cited by applicant]
Garber, “Bispecific antibodies rise again,” Nat. Rev. Drug Discov., 2014, 13:799-801.
[cited by applicant]
Gaulton et al., “Characterization of a monoclonal rat anti-mouse interleukin 2 (IL-2) receptor antibody and its use in the biochemical characterization of the murine IL-2 receptor,” Clinical Immunology and Immunopatholo…
[cited by applicant]
Gejima et al., “Human single-chain Fv (scFv) antibody specific to human IL-6 with the inhibitory activity on IL-6-signaling,” Human Antibodies, Jan. 1, 2002, 11(4):121-9.
[cited by applicant]
Geng et al., “A novel anti-TNF scFv constructed with human antibody frameworks and antagonistic peptides,” Immunol. Res. 62(3):377-385, 2015.
[cited by applicant]
Georgilis et al., “PTBP1-Mediated Alternative Splicing Regulates the Inflammatory Secretome and the Pro-tumorigenic Effects of Senescent Cells,” Cancer Cell, Jul. 9, 2018, 34(1):85-102.
[cited by applicant]
Ghosh et al., “The Senescence-Associated Secretory Phenotype: Critical Effector in Skin Cancer and Aging,” Journal of Investigative Dermatology, Nov. 2016, 136(11):2133-2139.
[cited by applicant]
Gibbs et al., “Identification of the factor VIIa binding site on tissue factor by homologous loop swap and alanine scanning mutagenesis,” Biochemistry, Nov. 1, 1994, 33(47):14003-10.
[cited by applicant]
Gong et al., “DAMP-sensing receptors in sterile inflammation and inflammatory diseases,” Nature Reviews Immunology, Sep. 26, 2019, 20(2):95-112.
[cited by applicant]
Gorrell et al., “Expression of the rat CD26 Antigen (dipeptidyl peptidase IV) on subpopulations of rat lymphocytes,” Cellular Immunology, Apr. 15, 1991, 134(1):205-215.
[cited by applicant]
Greenspan et al., “Defining epitopes: Its not as easy as it seems,” Nature Biotechnology, 1999, 17:936-937.
[cited by applicant]
Grupp et al., “Chimeric Antigen Receptor-Modified T Cells for Acute Lymphoid Leukemia,” The New England Journal of Medicine, Apr. 18, 2013, 368(16):1509-1518.
[cited by applicant]
Gu et al., “Human CD39hi regulatory T cells present stronger stability and function under inflammatory conditions,” Cellular and Molecular Immunology, Jul. 4, 2016, 14(6):521-528.
[cited by applicant]
Guo et al., “Immunobiology of the IL-15-IL-15R complex as an antitumor and antiviral agent,” 2017, Cytokine & Growth Factor Reviews, 38:10-21.
[cited by applicant]
Gutschmidt et al., “A quantitative histochemical study of dipeptidyl peptidase IV (DPP IV),” Histochemistry, 1981, 73(2):285-304.
[cited by applicant]
Haile et al., “Soluble CD80 Restores T Cell Activation and Overcomes Tumor Cell Programmed Death Ligand 1-Mediated Immune Suppression,” J. Immunol., 2013, 191(5):2829-2836.
[cited by applicant]
Hayflick et al., “The serial cultivation of human diploid cell strains,” Experimental Cell Research, Dec. 1961, 25:585-621.
[cited by applicant]
He et al., “Senescence in Health and Disease,” Cell, Jun. 1, 2017, 169(6):1000-1011.
[cited by applicant]
Hebbar et al., “Detection of circulating soluble CD28 in patients with systemic lupus erythematosus, primary Sjögren's syndrome and systemic sclerosis,” Clinical & Experimental Immunology, May 2004, 136(2):388-92.
[cited by applicant]
Helfrich et al., “A rapid and versatile method for harnessing scFv antibody fragments with varous biological effector functions,” Journal of Immunological methods, 2000, 237(1-2):131-145 DOI:1O.1O16/S0022-1759(99)OO220-…
[cited by applicant]
Heneka et al., “Inflammasome signaling in brain function and neurodegenerative disease,” Nature Reviews Neuroscience, Sep. 11, 2018, 19(10):610-621.
[cited by applicant]
Heneka et al., “NLRP3 is activated in Alzheimer's disease and contributes to pathology in APP/PS1 mice,” Nature, Jan. 31, 2013, 493(7434):674-678, 8 pages.
[cited by applicant]
Heng et al., “G Protein-Coupled Receptors Revisited: Therapeutic Applications Inspired by Synthetic Biology,” Annual Review of Pharmacology and Toxicology, Jan. 2014, 54:227-249.
[cited by applicant]
Heng et al., Sophea, et al. “Multiple soluble TGF-β receptors in addition to soluble endoglin are elevated in preeclamptic serum and they synergistically inhibit TGF-β signalling.” Placenta, 2017 57:320 (1 page).
[cited by applicant]
Highfill et al., “Overcoming Challenges in Process Development of Cellular Therapies,” Current Hematologic Malignancy Reports, Jul. 6, 2019, 14(4):269-277, 9 pages.
[cited by applicant]
Hoare et al., “The Power Behind the Throne: Senescence and the Hallmarks of Cancer,” Annual Review of Cancer Biology, 2018, 2:175-194.
[cited by applicant]
Hoffmann et al., “Large-scale in vitro expansion of polyclonal human CD4+CD25high regulatory T Cells,” Blood, Aug. 2004, 104(3):895-903.
[cited by applicant]
Hollande et al., “Inhibition of the dipeptidyl peptidase DPP4 (CD26) reveals IL-33-dependent eosinophil-mediated control of tumor growth,” Nature Immunology, Feb. 18, 2019, 20(3):257-264.
[cited by applicant]
Hombach et al., “Generation of the single chain antibody fragment conserves the idiotypic profile of the anti-CD30 monoclonal antibody HRS3,” Scandinavian Journal of Immunology, Nov. 1998, 48(5):497-501.
[cited by applicant]
Hu et al., “Discovery of a novel IL-15 based protein with improved developability and efficacy for cancer immunotherapy,” Scientific Reports, 2018, 8:7675, 11 pages.
[cited by applicant]
Huang et al., “Substrate recognition by tissue factor-factor VIIa Evidence for interaction of residues Lys165 and Lys166 of tissue factor with the 4-carboxyglutamate-rich domain of factor X,” Journal of Biological Chemi…
[cited by applicant]
Hudak et al., “Glycocalyx engineering reveals a Siglec-based mechanism for NK cell immunoevasion,” Nature Chemical Biology, Jan. 2014, 10(1), 20 pages.
[cited by applicant]
Hudson et al., “Targeting RAGE Signaling in Inflammatory Disease,” Annual Review of Medicine, Jan. 2018, 69:349-364, 16 pages.
[cited by applicant]
Huell et al., “Interleukin-6 is present in early stages of plaque formation and is restricted to the brains of Alzheimer's disease patients,” Acta Neuropathologica, Nov. 1995, 89(6):544-551.
[cited by applicant]
Hughes, et al., “Transfer of a TCR gene derived from a patient with a marked antitumor response conveys highly active T-cell effector functions,” Hum. Gene Ther., 2005, 16:457-72.
[cited by applicant]
Hynes et al., “In vitro analysis of cell metabolism using a long-decay pH-sensitive lanthanide probe and extracellular acidification assay,” Analytical biochemistry, Jul. 1, 2009, 390(1):21-28.
[cited by applicant]
Iannello et al., “p53-dependent chemokine production by senescent tumor cells supports NKG2D-dependent tumor elimination by natural killer cells,” Journal of Experimental Medicine, Sep. 23, 2013, 210(10):2057-69.
[cited by applicant]
Iihoshi et al., “Aclarubicin, an anthracycline anti-cancer drug, fluorescently contrasts mitochondria and reduces the oxygen consumption rate in living human cells,” Toxicology Letters, Aug. 5, 2017, 277:109-114, 22 pag…
[cited by applicant]
Inzucchi et al., “New Drugs for the Treatment of Diabetes, Part II: Incretin-Based Therapy and Beyond,” Circulation, Jan. 29, 2008, 117(4):574-584, 21 pages.
[cited by applicant]
Jain et al., “Mitochondrial Reactive Oxygen Species Regulate Transforming Growth Factor-β Signaling,” Journal of Biological Chemistry, Jan. 11, 2013, 288(2):770-777.
[cited by applicant]
Jakob et al., “Structure reveals function of the dual variable domain immunoglobulin (DVD-Ig™) molecule,” Mabs, May 1, 2013, Taylor & Francis, 5(3):358-63.
[cited by applicant]
Janeway, “Approaching the Asymptote? Evolution and Revolution in Immunology,” Cold Spring Harbor Symposia on Quantitative Biology, 1989, 54 Pt 1:1-13.
[cited by applicant]
Jeannin et al., “Soluble CD86 Is a Costimulatory Molecule for Human T Lymphocytes,” Immunity, 2000, 13(3):303-312.
[cited by applicant]
Jin et al., “Novel Insights Into the NLRP3 Inflammasome in Atherosclerosis,” Journal of the American Heart Association, Jun. 11, 2019, 8(12):e012219, 12 pages.
[cited by applicant]
Justice et al., “Senolytics in idiopathic pulmonary fibrosis: Results from a first-in-human, open-label, pilot study,” EBioMedicine, Feb. 2019, 40:554-563.
[cited by applicant]
Kain et al., “The identification of the endogenous ligands of natural killer T cells reveals the presence of mammalian α-linked glycosylceramides,” Immunity, Oct. 16, 2014, 41(4):543-54.
[cited by applicant]
Karin et al., “Senescent cell turnover slows with age providing an explanation for the Gompertz law,” Nature Communications, 10:5495, 9 pages.
[cited by applicant]
Karkera et al., “The anti-interleukin-6 antibody siltuximab down-regulates genes implicated in tumorigenesis in prostate cancer patients from a phase I study,” The Prostate, Feb. 14, 2011, 71(13):1455-1465.
[cited by applicant]
Katsuumi et al., “Vascular Senescence in Cardiovascular and Metabolic Diseases,” Frontiers in Cardiovascular Medicine, 5:18, 13 pages.
[cited by applicant]
Kellner et al., “Enhancing natural killer cell-mediated lysis of lymphoma cells by combining therapeutic antibodies with CD20-specific immunoligands engaging NKG2D or NKp30,” Oncoimmunology, Jan. 2, 2016, 5(1):e1058459,…
[cited by applicant]
Kijanka et al., “Nanobody-based cancer therapy of solid tumors,” Nanomedicine, Jan. 2015, 10(1):161-74.
[cited by applicant]
Kim et al., “Experimental malaria infection triggers early expansion of natural killer cells,” Infection and Immunity, Dec. 1, 2008, 76(12):5873-82.
[cited by applicant]
Kim et al., “Identification of senescent cell surface targetable protein DPP4,” Genes & Development, 2017, 31(15):1529-1534.
[cited by applicant]
Kim et al., “SCAMP4 enhances the senescent cell secretome,” Genes & Development, 2018, 32(13-14):909-914.
[cited by applicant]
Kirchhofer et al., “The tissue factor region that interacts with substrates factor IX and factor X,” Biochemistry, Jun. 27, 2000, 39(25):7380-7.
[cited by applicant]
Kirkland et al., “Cellular Senescence: A Translational Perspective,” EBioMedicine, Jul. 2017, 21:21-28.
[cited by applicant]
Klein et al., “Cergutuzumab amunaleukin (CEA-IL2v), a CEA-targeted IL-2 variant-based immunocytokine for combination cancer immunotherapy: Overcoming limitations of aldesleukin and conventional IL-2-based immunocytokine…
[cited by applicant]
Klein et al., “Design and characterization of structured protein linkers with differing flexibilities,” Protein Engineering, Design & Selection, 2014, 27(10):325-30.
[cited by applicant]
Klemann et al., “Cut to the chase: a review of CD26/dipeptidyl peptidase-4's (DPP4) entanglement in the immune system,” Clinical and Experimental Immunology, Feb. 25, 2016, 185(1):1-21.
[cited by applicant]
Klingenberg et al., “Depletion of FOXP3+ regulatory T cells promotes hypercholesterolemia and atherosclerosis,” The Journal of Clinical Investigation, Feb. 15, 2013, 123:1323-1334.
[cited by applicant]
Kondo et al., “Requirements for the functional expression of OX40 ligand on human activated CD4+ and CD8+ T cells,” Human Immunology, 2007, 68(7):563-571.
[cited by applicant]
Kovaleva et al., “Shark variable new antigen receptor biologics—a novel technology platform for therapeutic drug development,” Expert Opinion on Biological Therapy, Oct. 1, 2014, 14(10):1527-39.
[cited by applicant]
Krah et al., “Single-domain antibodies for biomedical applications,” Immunopharmacology and Immunotoxicology, Jan. 2, 2016, 38(1):21-8.
[cited by applicant]
Kritsilis et al., “Ageing, Cellular Senescence and Neurodegenerative Disease,” International Journal of Molecular Sciences, Sep. 27, 2018, 19(10):2937, 37 pages.
[cited by applicant]
Krizhanovsky et al., “Senescence of activated stellate cells limits liver fibrosis,” Cell, Aug. 22, 2008, 134(4):657-67.
[cited by applicant]
Kumagai et al., “Monitoring of glutamate-induced excitotoxicity by mitochondrial oxygen consumption,” Synapse, Jan. 2019, 73(1):e22067, 24 Pages.
[cited by applicant]
Lambeir et al., “Dipeptidyl-Peptidase IV from Bench to Bedside: An Update on Structural Properties, Functions, and Clinical Aspects of the Enzyme DPP IV,” Critical Reviews in Clinical Laboratory Sciences, Sep. 29, 2003,…
[cited by applicant]
Lamkanfi et al., “Mechanisms and Functions of Inflammasomes,” Cell, May 22, 2014, 157(5):1013-1022.
[cited by applicant]
Lansigan et al., “DI-Leu16-IL2, an Anti-CD20-Interleukin-2 Immunocytokine, Is Safe and Active in Patients with Relapsed and Refractory B-Cell Lymphoma: A Report of Maximum Tolerated Dose, Optimal Biologic Dose, and Reco…
[cited by applicant]
Latz et al., “Activation and regulation of the inflammasomes,” Nature Reviews Immunology, May 24, 2013, 13(6):397-411.
[cited by applicant]
Latz et al., “NLRP3 inflammasome activation in inflammaging,” Seminars in Immunology, Dec. 2018, 40:61-73, 13 pages.
[cited by applicant]
Lau et al., “RNA-associated autoantigens activate B cells by combined B cell antigen receptor/Toll-like receptor 7 engagement,” The Journal of Experimental Medicine, Oct. 31, 2005, 202(9):1171-1177.
[cited by applicant]
Lazar et al., “Transforming Growth Factor Alpha: Mutation of Aspartic Acid 47 and Leucine 48 Results in Different Biological Activities,” Mol. Cell. Biol., 1988, 8:1247-1252.
[cited by applicant]
Li et al., “A Novel I L2-based Immunotherapeutic Protein Prevents the Development of Atherosclerosis in ApoE-/mice and LDLR-/- mice,” Journal of Immunology, May 1, 2020, 204(1):Supplement (Abstract Only), 2 pages.
[cited by applicant]
Li et al., “Adoptive transfer of natural killer cells in combination with chemotherapy improves outcomes of patients with locally advanced colon carcinoma,” Cytotherapy, Jan. 2018, 20(1):134-148, 15 pages.
[cited by applicant]
Li et al., “The cGAS-cGAMP-STING pathway connects DNA damage to inflammation, senescence, and cancer,” Journal of Experimental Medicine, Apr. 5, 2018, 215(5):1287-1299.
[cited by applicant]
Liton et al., “Cellular senescence in the glaucomatous outflow pathway,” Experimental Gerontology, Aug.-Sep. 2005, 40(8-9):745-748.
[cited by applicant]
Liu et al., “A Novel Fusion of ALT-803 (IL-15 Superagonist) with an Antibody Demonstrates Antigen-specific Antitumor Responses,” Journal of Biological Chemistry, 2016, 291(46):23869-23881.
[cited by applicant]
Liu et al., “Evaluation of the biological activities of the IL-15 superagonist complex, ALT-803, following intravenous versus subcutaneous administration in murine models,” Cytokine, Jul. 2018, 107: 105-112, 8 pages.
[cited by applicant]
Loster et al., “The Cysteine-Rich Region of Dipeptidyl Peptidase IV (CD 26) Is the Collagen Binding Site,” Biochemical and Biophysical Research Communications, Dec. 5, 1995, 217(1):341-348.
[cited by applicant]
Lu et al., “Molecular basis of binding between novel human coronavirus MERS-CoV and its receptor CD26,” Nature, Jul. 7, 2013, 500(7461):227-231.
[cited by applicant]
Lujambio et al., “Non-Cell-Autonomous Tumor Suppression by p53,” Cell, Apr. 11, 2013, 153(2):449-460.
[cited by applicant]
Maeda et al., “Original Ligand for LTβR Is LIGHT: Insight into Evolution of the LT/LTβR System,” J Immunol., 2018, 201(1):202-214.
[cited by applicant]
Maganto-García et al., “Dynamic Changes in Regulatory T Cells Are Linked to Levels of Diet-Induced Hypercholesterolemia,” Circulation, Jun. 20, 2011, 124:185-195.
[cited by applicant]
Mandelboim et al., “Recognition of haemaglutinins on virus-infected cells by NKp46 activates lysis by human NK cells,” Nature, Feb. 2001, 409(6823):1055.
[cited by applicant]
Marguet et al., “Enhanced insulin secretion and improved glucose tolerance in mice lacking CD26,” Proc. Natl. Acad. Sci. U.S.A., Jun. 6, 2000, 97(12):6874-6879.
[cited by applicant]
Martelli et al., “HLA-haploidentical transplantation with regulatory and conventionalT-cell adoptive immunotherapy prevents acute leukemia relapse,” Blood, Jul. 24, 2014, 124(4):638-644.
[cited by applicant]
Masoumi et al., “The role of hypoxia as the driving force for non-erythroid production of globin chains in preeclamptic placentas,” Placenta. 2017;57:320.
[cited by applicant]
McHugh et al., “Senescence and aging: Causes, consequences, and therapeutic avenues,” Journal of Cellular Biology, Nov. 7, 2017, 217(1):65-77.
[cited by applicant]
Mehta et al., “Why do trials for Alzheimer's disease drugs keep failing? A discontinued drug perspective for 2010-2015,” Expert Opinion on Investigational Drugs, May 2017, 26(6):735-739.
[cited by applicant]
Menshawy et al., “CD58; leucocyte function adhesion-3 (LFA-3) could be used as a differentiating marker between immune and non-immune thyroid disorders,” Comparative Clinical Pathology, 2018, 27(3), 721-727, doi.org/10.…
[cited by applicant]
Mentlein et al., “Dipeptidyl-peptidase IV (CD26)-role in the inactivation of regulatory peptides,” Regulatory Peptides, Nov. 30, 1999, 85(1):9-24.
[cited by applicant]
Miah et al., “KIR2DL4 differentially signals downstream functions in human NK cells through distinct structural modules,” The Journal of Immunology, Mar. 1, 2008, 180(5):2922-32.
[cited by applicant]
Michelet et al., “Metabolic reprogramming of natural killer cells in obesity limits antitumor responses,” Nature Immunology, Nov. 12, 2018, 19(12):1330-1340.
[cited by applicant]
Milanovic et al., “Senescence-associated reprogramming promotes cancer stemness,” Nature, Dec. 20, 2017, 553(7686):96-100.
[cited by applicant]
Milanovic et al., “The Senescence-Stemness Alliance—A Cancer-Hijacked Regeneration Principle,” Trends in Cellular Biology, Dec. 2018, 28(12):1049-1061, 13 pages.
[cited by applicant]
Miller et al., “Soluble CD70: a novel immunotherapeutic agent for experimental glioblastoma,” J Neurosurg., 2010, 113(2):280-285.
[cited by applicant]
Miller et al., “Successful adoptive transfer and in vivo expansion of human haploidentical NK cells in patients with cancer,” Blood, Apr. 15, 2005, 105(8):3051-3057.
[cited by applicant]
Minamino et al., “A crucial role for adipose tissue p53 in the regulation of insulin resistance,” Nature Medicine, Aug. 30, 2009, 15(9):1082-1087.
[cited by applicant]
Mitterberger et al., “Adipogenic Differentiation Is Impaired in Replicative Senescent Human Subcutaneous Adipose-Derived Stromal/Progenitor Cells,” The Journals of Gerontology: Series A, Biological Sciences and Medical …
[cited by applicant]
Miyazaki et al., “Abstract 3265: NKTR-255, a polymer-conjugated IL-15 enhances anti-tumor NK cell responses and synergizes with monoclonal antibodies to provide long-term survival in human lymphoma model,” Proceedings: …
[cited by applicant]
Moesta et al., “Targeting CD39 in cancer,” Nature Reviews Immunology, Jul. 29, 2020, 20(12):739-755, 17 pages.
[cited by applicant]
Moiseeva et al., “Metformin inhibits the senescence-associated secretory phenotype by interfering with IKK/NF-κB activation,” Aging Cell, Mar. 23, 2013, 12(3):489-498.
[cited by applicant]
Molema et al., “The use of bispecific antibodies in tumor cell and tumor vasculature directed immunotherapy,” Journal of Controlled Release, 2000, 64(1-3):229-239.
[cited by applicant]
Molgora et al., “Regulatory role of IL-1R8 in immunity and disease,” Frontiers in Immunology, Apr. 20, 2016, 7:149.
[cited by applicant]
Mookerjee et al., “Measurement and Analysis of Extracellular Acid Production to Determine Glycolytic Rate,” Journal of Visualized Experiments : Jove, Dec. 2015, (106):e53464, 9 Pages.
[cited by applicant]
Moore et al., “Macrophages in atherosclerosis: a dynamic balance,” Nature Reviews Immunology, Sep. 2, 2013, 13:709-721, 13 pages.
[cited by applicant]
Moreno et al., “Molecular Evidence of Adenosine Deaminase Linking Adenosine A2A Receptor and CD26 Proteins,” Frontiers in Pharmacology, Feb. 15, 2018, 9:106, 18 pages.
[cited by applicant]
Moretta et al., “CD69-mediated pathway of lymphocyte activation: anti-CD69 monoclonal antibodies trigger the cytolytic activity of different lymphoid effector cells with the exception of cytolytic T lymphocytes expressi…
[cited by applicant]
Mujić-Delić et al., “GPCR-targeting nanobodies: attractive research tools, diagnostics, and therapeutics,” Trends in Pharmacological Sciences, May 1, 2014, 35(5):247-55.
[cited by applicant]
Muller et al., “Antibody fusions with immunomodulatory proteins for cancer therapy,” Pharmacology and Therapeutics, 2015, 154:57-66.
[cited by applicant]
Mulvihill et al., “Pharmacology, Physiology, and Mechanisms of Action of Dipeptidyl Peptidase-4 Inhibitors,” Endocrine Reviews, Dec. 1, 2014, 35(6):992-1019.
[cited by applicant]
Munoz-Espin et al., “Cellular senescence: from physiology to pathology,” Nature Reviews Molecular Cellular Biology, Jun. 23, 2014, 15(7):482-496.
[cited by applicant]
Munoz-Espin et al., “Programmed Cell Senescence during Mammalian Embryonic Development,” Cell, Nov. 21, 2013, 155(5):1104-1118.
[cited by applicant]
Musi et al., “Tau protein aggregation is associated with cellular senescence in the brain,” Aging Cell, Aug. 20, 2018, 17(6):e12840, 13 pages.
[cited by applicant]
Must et al., “The Disease Burden Associated with Overweight and Obesity,” Endotext, Feingold et al. (eds.), South Dartmouth, MA, 2000, 35 pages.
[cited by applicant]
Muyldermans et al., “Recognition of antigens by single-domain antibody fragments: the superfluous luxury of paired domains,” Trends in Biochemical Sciences, Apr. 1, 2001, 26(4):230-5.
[cited by applicant]
Muyldermans, “Nanobodies: natural single-domain antibodies,” Annual Review of Biochemistry, Jun. 2, 2013, 82:775-97.
[cited by applicant]
Muyldermans, “Single domain camel antibodies: current status,” Reviews in Molecular Biotechnology, Jun. 1, 2001, 74(4):277-302.
[cited by applicant]
Myung et al., “Evidence of DNA damage in Alzheimer disease: phosphorylation of histone H2AX in astrocytes,” Age, Apr. 23, 2008, 30(4):209-215.
[cited by applicant]
Nag et al., “Soluble MHC II-peptide complexes induce antigen-specific apoptosis in T cells,” Cellular Immunology, May 25, 1996, 170(1):25-33.
[cited by applicant]
Nayyar et al., “Overcoming Resistance to Natural Killer Cell Based Immunotherapies for Solid Tumors,” Frontiers in Oncology, 2019, 9: DOI:10.3389/fonc.2019.00051.
[cited by applicant]
Nelson et al., “A senescent cell bystander effect: senescence-induced senescence,” Aging Cell, Feb. 9, 2012, 11(2):345-349.
[cited by applicant]
Nilsson et al., “Targeted delivery of tissue factor to the ED-B domain of fibronectin, a marker of angiogenesis, mediates the infarction of solid tumors in mice,” Cancer Research, American Association for Cancer Researc…
[cited by applicant]
Nishida et al., “CD26 is a potential therapeutic target by humanized monoclonal antibody for the treatment of multiple myeloma,” Blood Cancer Journal, Oct. 22, 2018, 8(11):99, 17 pages.
[cited by applicant]
O'Sullivan et al., “Natural Killer Cell Memory,” Immunity, Oct. 20, 2015, 43(4):634-645.
[cited by applicant]
Oberle et al., “Rapid Suppression of Cytokine Transcription in Human CD4+CD25-T Cells by CD4+Foxp3+ Regulatory T Cells: Independence of IL-2 Consumption, TGF-β, and Various Inhibitors of TCR Signaling,” The Journal of I…
[cited by applicant]
Ogrodnik et al., “Cellular senescence drives age-dependent hepatic steatosis,” Nat Commun. Jun. 13, 2017;8:15691, 12 pages.
[cited by applicant]
Ogrodnik et al., “Obesity-Induced Cellular Senescence Drives Anxiety and Impairs Neurogenesis,” Cell Metabolism, May 2019, 29(5):1061-1077, 25 pages.
[cited by applicant]
Ohnuma et al., “Blockade of CD26-mediated T cell costimulation with soluble caveolin-1-Ig fusion protein induces anergy in CD4+T cells,” Biochemical and Biophysics Research Communications, Aug. 21, 2009, 386(2):327-332.
[cited by applicant]
Ohnuma et al., “CD26 Mediates Dissociation of Tollip and IRAK-1 from Caveolin-1 and Induces Upregulation of CD86 on Antigen-Presenting Cells,” Molecular and Cellular Biology, Sep. 1, 2005, 25(17):7743-7757.
[cited by applicant]
Ohnuma et al., “CD26 up-regulates expression of CD86 on antigen-presenting cells by means of caveolin-1,” Proc. Natl. Acad. Sci. U.S.A., Sep. 28, 2004, 101(39):14186-14191.
[cited by applicant]
Ohnuma et al., “Role of CD26/dipeptidyl peptidase IV in human T cell activation and function,” Frontiers in Bioscience, Jan. 1, 2008, 13:2299-2310.
[cited by applicant]
Ohnuma et al., “Soluble CD26/Dipeptidyl Peptidase IV Induces T Cell Proliferation Through CD86 Up-Regulation on APCs,” Journal of Immunology, Dec. 15, 2001, 167(12):6745-6755.
[cited by applicant]
Ovadya et al., “Strategies targeting cellular senescence,” The Journal of Clinical Investigation, Apr. 2, 2018, 128(4):1247-54.
[cited by applicant]
Owicki et al., “Biosensors based on the energy metabolism of living cells: the physical chemistry and cell biology of extracellular acidification,” Biosensors and Bioelectronics, Jan. 1, 1992, 7(4):255-272.
[cited by applicant]
Padutsch et al., “Superior Treg-Expanding Properties of a Novel Dual-Acting Cytokine Fusion Protein,” Frontiers in Pharmacology, Dec. 18, 2019, 10:1490, 10 pages.
[cited by applicant]
Palmer et al., “Cellular Senescence in Type 2 Diabetes: A Therapeutic Opportunity,” Diabetes, Jul. 2015, 64(7):2289-2298.
[cited by applicant]
Parker et al., “Design, production, and characterization of a single-chain variable fragment (ScFv) derived from the prostate specific membrane antigen (PSMA) monoclonal antibody J591,” Protein Expression and Purificati…
[cited by applicant]
PCT International Preliminary Report on Patentability in International Appln. No. PCT/US2019/048881, dated Mar. 11, 2021, 7 pages.
[cited by applicant]
PCT International Preliminary Report on Patentability in International Appln. No. PCT/US2019/048930, dated Mar. 11, 2021, 9 pages.
[cited by applicant]