IP Library Granted Patent US 12,516,112
Granted Patent B2
US 12,516,112 · App. 18/669,092 · Granted Jan 6, 2026

Single-chain chimeric polypeptides and uses thereof

Inventor: Hing Wong (Miramar, FL)
Assignee: ImmunityBio, Inc.
C07K16/18A61K39/00A61P3/10C07K16/2809C07K16/2818C07K16/2866C12N5/0636C12N5/0637C07K2317/24C07K2317/56C07K2317/622C07K2319/00C12N2501/998
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Quick Facts
Patent No.
US 12,516,112
App. No.
18/669,092
Granted
Jan 6, 2026
Kind
B2
Abstract

Provided herein are single-chain chimeric polypeptides that include: (i) a first target-binding domain; (ii) a soluble tissue factor domain; and (iii) a second target-binding domain. Also provided here are methods of using these single-chain chimeric polypeptides and nucleic acids encoding these single-chain chimeric polypeptides.

Claims (34)

1 . A method of treating a subject having hyperglycemia, the method comprising administering to the subject a therapeutically effective amount of a single-chain chimeric polypeptide comprising:

(i) a first target-binding domain comprising a sequence that is at least 80% identical to SEQ ID NO: 28;

(ii) a soluble tissue factor domain comprising a sequence that is at least 80% identical to SEQ ID NO: 9 and does not initiate blood coagulation; and

(iii) a second target-binding domain comprising a sequence that is at least 80% identical to SEQ ID NO: 28;

wherein the first target-binding domain and the second target-binding domain comprise interleukin-2 (IL-2), and

wherein the single-chain chimeric polypeptide does not stimulate blood coagulation in a mammal.

2 . The method of claim 1 , wherein the first target-binding domain and the soluble tissue factor domain directly abut each other.

3 . The method of claim 1 , wherein the single-chain chimeric polypeptide further comprises a linker sequence between the first target-binding domain and the soluble tissue factor domain.

4 . The method of claim 1 , wherein the soluble tissue factor domain and the second target-binding domain directly abut each other.

5 . The method of claim 1 , wherein the single-chain chimeric polypeptide further comprises a linker sequence between the soluble tissue factor domain and the second target-binding domain.

6 . The method of claim 1 , wherein:

the first target-binding domain comprises a sequence that is at least 90% identical to SEQ ID NO: 28;

the soluble tissue factor domain comprises a sequence that is at least 90% identical to SEQ ID NO: 9, and

the second target-binding domain comprises a sequence that is at least 90% identical to SEQ ID NO: 28.

7 . The method of claim 6 , wherein:

the first target-binding domain comprises a sequence that is at least 95% identical to SEQ ID NO: 28;

the soluble tissue factor domain comprises a sequence that is at least 95% identical to SEQ ID NO: 9; and

the second target-binding domain comprises a sequence that is at least 95% identical to SEQ ID NO: 28.

8 . The method of claim 7 , wherein:

the first target-binding domain comprises SEQ ID NO: 28;

the soluble tissue factor domain comprises SEQ ID NO: 9; and

the second target-binding domain comprises SEQ ID NO: 28.

9 . The method of claim 1 , wherein the soluble tissue factor domain is a soluble human tissue factor domain that does not have coagulation activity.

10 . The method of claim 1 , wherein the single-chain chimeric polypeptide comprises a sequence that is at least 90% identical to SEQ ID NO: 108.

11 . The method of claim 10 , wherein the single-chain chimeric polypeptide comprises a sequence that is at least 95% identical to SEQ ID NO: 108.

12 . The method of claim 11 , wherein the single-chain chimeric polypeptide comprises SEQ ID NO: 108.

13 . The method of claim 1 , wherein the single-chain chimeric polypeptide comprises a sequence that is at least 90% identical to SEQ ID NO: 110.

14 . The method of claim 13 , wherein the single-chain chimeric polypeptide comprises a sequence that is at least 95% identical to SEQ ID NO: 110.

15 . The method of claim 14 , wherein the single-chain chimeric polypeptide comprises SEQ ID NO: 110.

16 . The method of claim 1 , wherein the single-chain chimeric polypeptide comprises a sequence that is at least 80% identical to SEQ ID NO: 108.

17 . The method of claim 1 , wherein the single-chain chimeric polypeptide comprises a sequence that is at least 80% identical to SEQ ID NO: 110.

18 . The method of claim 1 , wherein fasting blood glucose levels are lowered.

19 . The method of claim 1 , wherein insulin resistance is reduced.

20 . The method of claim 1 , wherein the subject has type 2 diabetes mellitus.

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 May 23, 2024
From: WONG, HING
To: HCW BIOLOGICS, INC.
Reel/Frame 067508/0043 →
Continuity (10)
Continuation 17870373 · Jul 21, 2022
Division 16556040 · Aug 29, 2019
Provisional Application 62881039 · Jul 31, 2019
Provisional Application 62817241 · Mar 12, 2019
Provisional Application 62817244 · Mar 12, 2019
Provisional Application 62816683 · Mar 11, 2019
Provisional Application 62749506 · Oct 23, 2018
Provisional Application 62746832 · Oct 17, 2018
Provisional Application 62725038 · Aug 30, 2018
Related Publication 20240376187A1 · Nov 14, 2024
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 · 2010 [cited by examiner]
US 7723482B2 · Soulillou et al. · 2010 [cited by applicant]
US 7968094B2 · Jiao et al. · 2011 [cited by applicant]
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 11518792B2 · Wong · 2022 [cited by applicant]
US 11672826B2 · Wong · 2023 [cited by applicant]
US 11730762B2 · Wong · 2023 [cited by applicant]
US 11738052B2 · Wong · 2023 [cited by applicant]
US 20010044427A1 · Mazel et al. · 2001 [cited by applicant]
US 20030124678A1 · Epstein et al. · 2003 [cited by applicant]
US 20030219441A1 · Thorpe et al. · 2003 [cited by applicant]
US 20050014224A1 · Collins et al. · 2005 [cited by applicant]
US 20060159655A1 · Collins et al. · 2006 [cited by applicant]
US 20070160579A1 · Schmitz et al. · 2007 [cited by applicant]
US 20080025979A1 · Honjo et al. · 2008 [cited by applicant]
US 20090148942A1 · McDonagh et al. · 2009 [cited by applicant]
US 20120171197A1 · Eriksson et al. · 2012 [cited by applicant]
US 20120264920A1 · Wang et al. · 2012 [cited by applicant]
US 20130274446A1 · Kumagai et al. · 2013 [cited by applicant]
US 20140242077A1 · Choi · 2014 [cited by applicant]
US 20150218274A1 · Sabatos-Peyton et al. · 2015 [cited by applicant]
US 20150259429A1 · Benaroch et al. · 2015 [cited by applicant]
US 20160175397A1 · Umana et al. · 2016 [cited by applicant]
US 20160340413A1 · Duerner et al. · 2016 [cited by applicant]
US 20160367664A1 · Wang et al. · 2016 [cited by applicant]
US 20170051063A1 · Baum et al. · 2017 [cited by applicant]
US 20170198042A1 · Williams et al. · 2017 [cited by applicant]
US 20170283499A1 · Delhem et al. · 2017 [cited by applicant]
US 20180200366A1 · Wong · 2018 [cited by applicant]
US 20190078082A1 · Amorese et al. · 2019 [cited by applicant]
US 20190092846A1 · Ibebunjo et al. · 2019 [cited by applicant]
US 20190177406A1 · Ledbetter et al. · 2019 [cited by applicant]
US 20190315850A1 · Bedinger et al. · 2019 [cited by applicant]
US 20200071374A1 · Wong · 2020 [cited by applicant]
US 20200123607A1 · Serrano Marugan et al. · 2020 [cited by applicant]
US 20200392221A1 · Van Snick et al. · 2020 [cited by applicant]
US 20200399358A1 · Shapiro et al. · 2020 [cited by applicant]
US 20210060064A1 · Wong · 2021 [cited by applicant]
US 20210061897A1 · Ledbetter et al. · 2021 [cited by applicant]
US 20210070825A1 · Wong · 2021 [cited by applicant]
US 20210070826A1 · Wong · 2021 [cited by applicant]
US 20210100840A1 · Wong et al. · 2021 [cited by applicant]
US 20210137981A1 · Wong · 2021 [cited by applicant]
US 20210268022A1 · Wong et al. · 2021 [cited by applicant]
US 20210277054A1 · Wong et al. · 2021 [cited by applicant]
US 20210338724A1 · Wong · 2021 [cited by applicant]
US 20210355204A1 · Bedinger et al. · 2021 [cited by applicant]
US 20210403545A1 · Van Snick et al. · 2021 [cited by applicant]
US 20220073578A1 · Wong et al. · 2022 [cited by applicant]
US 20230039157A1 · Wong · 2023 [cited by applicant]
US 20230128292A1 · Wong · 2023 [cited by applicant]
US 20230174666A1 · Wong et al. · 2023 [cited by applicant]
US 20230272027A1 · Wong · 2023 [cited by applicant]
US 20230372399A1 · Wong · 2023 [cited by applicant]
US 20230372444A1 · Wong et al. · 2023 [cited by applicant]
US 20230381238A1 · 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 101653603 · 2010 [cited by applicant]
CN 101965364 · 2011 [cited by applicant]
CN 102153653 · 2011 [cited by applicant]
CN 1844150 · 2016 [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 WO2020047462 · 2020 [cited by applicant]
WO WO2020047473 · 2020 [cited by applicant]
WO WO2021163369 · 2021 [cited by applicant]
Diaz-de-Durana, Yaiza, et al. “IL-2 immunotherapy reveals potential for innate beta cell regeneration in the non-obese diabetic mouse model of autoimmune diabetes.” PloS one 8.10 (2013): e78483 (Year: 2013). [cited by examiner]
Chaudhury, Arun, et al. “Clinical review of antidiabetic drugs: implications for type 2 diabetes mellitus management.” Frontiers in endocrinology 8 (2017): 6 (Year: 2017). [cited by examiner]
Teng, Shaolei et al. International journal of computational biology and drug design vol. 3,4 (2010): 334-49 (Year: 2010). [cited by examiner]
Stryer, Biochemistry 4th, WH Freeman, New York. 1995 (Year: 1995). [cited by examiner]
Tam, James P., Jiaxi Xu, and Khee Dong Eom. “Methods and strategies of peptide ligation.” Peptide Science: Original Research on Biomolecules 60.3 (2001): 194-205. (Year: 2001). [cited by examiner]
Chandrudu S, Simerska P, Toth I. Chemical methods for peptide and protein production. Molecules. 2013;18(4):4373-4388. Published Apr. 12, 2013. doi: 10.3390/molecules18044373 (Year: 2013). [cited by examiner]
[No Author Listed], “CN Br-activated Sepharose 4 Fast Flow,” 1999, Affinity Chromatography, 4 pages. [cited by applicant]
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]
Ahmadi et al., “Tissue factor (coagulation factor III): a potential double-edge molecule to be targeted and re-targeted toward cancer,” Biomarker Research, Jun. 2023, 11(60):2-39. [cited by applicant]
Ait-Oufella et 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]
Bartscht et al., “Dasatinib blocks transcriptional and promigratory responses to transforming growth factor-beta in pancreatic adenocarcinoma cells through inhibition of Smad signalling: implications for in vivo mode of… [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. [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. [cited by applicant]
Bird et al., “TGFβ inhibition restores a regenerative response in acute liver injury by suppressing paracrine senescence,” Science translational medicine, Aug. 15, 2018, 10(454):eaan 1230, 15 pages. [cited by applicant]
Borea et al., “Pharmacology of Adenosine Receptors: The State of the Art,” Physiological Reviews, May 30, 2018, 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]
Brämer et al., “Membrane adsorber for the fast purification of a monoclonal antibody using protein a chromatography,” Membranes, Nov. 27, 2019, 9(12):159, 15 pages. [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. [cited by applicant]
Cai et al., “Chibby suppresses aerobic glycolysis and proliferation of nasopharyngeal carcinoma via the Wnt/B-catenin-Lin28/let7-PDK1 cascade,” Journal of Experimental & Clinical Cancer Research, Dec. 1, 2018, 37(1):104. [cited by applicant]
Cai et al., “Quercetin inhibits transforming growth factor β1-induced epithelial-mesenchymal transition in human retinal pigment epithelial cells via the Smad pathway,” Drug design, development and therapy, Dec. 6, 2018… [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]
Chabannon et al., “Manufacturing natural killer cells as medicinal products,” Frontiers in Immunology, Nov. 15, 2016, 7(504):1-9. [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]
Chan et al., “Molecular mechanisms of natural killer cell activation in response to cellular stress,” Cell Death & Differentiation, Jan. 2014, 21(1):5-14. [cited by applicant]
Chance et al., “A simple and rapid assay of oxidative phosphorylation,” Nature, Jun. 1955, 175(4469):1120-1121. [cited by applicant]
Chandrudu et al., “Chemical methods for peptide and protein production,” Molecules, 2013, 18(4):4373-4388. [cited by applicant]
Chang et al., “The dock and lock method: a novel platform technology for building multivalent, multifunctional structures of defined composition with retained bioactivity,” Clinical Cancer Research, Sep. 15, 2007, 13(18… [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., “A novel idea for establishing Parkinson's disease mouse model by intranasal administration of paraquat,” Neurological Research, 2021, 43(4):267-277. [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. [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 contributes 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. [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. [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 pag… [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:… [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. [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-B 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 in HLA-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 glycyl-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. [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., “Pre-association of IL-15 with IL-15Ra-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]
Fernando et al., “Targeting tumor endothelial marker 8 in the tumor vasculature of colorectal carcinomas in mice,” Cancer Research, Jun. 15, 2009, 69(12):5126-5132. [cited by applicant]
Ferreira et al., “Next-generation regulatory T cell therapy,” Nature Reviews Drug Discovery, Sep. 20, 2019, 18(10):749-769. [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 SkinCancer 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: It's 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]
Guha et al., “Affinity purification of human tissue factor: interaction of factor VII and tissue factor in detergent micelles,” Proceedings of the National Academy of Sciences, Jan. 1986, 83(2):299-302. [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 various biological effector functions,” Journal of Immunological methods, 2000, 237(1-2):131-145. [cited by applicant]
Hélie et al., “Application of the Protein Maker as a platform purification system for therapeutic antibody research and development,” Computational and Structural Biotechnology Journal, Jan. 1, 2016, 14:238-244. [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. [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., “Multiple soluble TGF-β receptors in addition to soluble endoglin are elevated in preeclamptic serum and they synergistically inhibit TGF-βsignalling.” Placenta, 2017 57:320. [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. [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]
Huang et al., “Targeting the vasculature of colorectal carcinoma with a fused protein of (RGD) 3-tTF” The Scientific World Journal, May 2013, 2013(637086):1-11. [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. [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]
Hui et al., “Butyrate inhibit collagen-induced arthritis via Treg/IL-10/Th17 axis,” International immunopharmacology, Mar. 1, 2019, 68: Abstract 1 page. [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]
Igarashi et al., “VEGF-C and TGF-β reciprocally regulate mesenchymal stem cell commitment to differentiation into lymphatic endothelial or osteoblastic phenotypes,” International Journal of Molecular Medicine, Apr. 1, 2… [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. [cited by applicant]
Infante-Duarte et al., “New developments in understanding and treating neuroinflammation,” Journal of Molecular Medicine, Sep. 2008, 86:975-985. [cited by applicant]
info.gbiosciences.com [Online], “G-Biosciences, The Basics of Affinity Purification/Affinity Chromatography,” Jul. 31, 2018, retrieved on Apr. 18, 2023, retrieved from URL<https://info.gbiosciences.com/blog/the-basics-o… [cited by applicant]
International Preliminary Report on Patentability in International Appln. No. PCT/US2019/048881, dated Mar. 11, 2021, 7 pages. [cited by applicant]
International Preliminary Report on Patentability in International Appln. No. PCT/US2019/048930, dated Mar. 11, 2021, 9 pages. [cited by applicant]
International Preliminary Report on Patentability in International Appln. No. PCT/US2019/049142, dated Mar. 11, 2021, 11 pages. [cited by applicant]
International Preliminary Report on Patentability in International Appln. No. PCT/US2019/049158, dated Mar. 11, 2021, 8 pages. [cited by applicant]
International Preliminary Report on Patentability in International Appln. No. PCT/US2020/035598, mailed Dec. 6, 2022, 7 pages. [cited by applicant]
International Preliminary Report on Patentability in International Appln. No. PCT/US2020/038717, dated Dec. 30, 2021, 9 pages. [cited by applicant]
International Preliminary Report on Patentability in International Appln. No. PCT/US2021/017620, dated Aug. 25, 2022, 12 pages. [cited by applicant]
International Preliminary Report on Patentability in International Appln. No. PCT/US2021/017621, dated Aug. 25, 2022, 8 pages. [cited by applicant]
International Preliminary Report on Patentability in International Appln. No. PCT/US2021/017714, dated Aug. 25, 2022, 12 pages. [cited by applicant]
International Preliminary Report on Patentability in International Appln. No. PCT/US2021/029920, dated Nov. 10, 2022, 11 pages. [cited by applicant]
International Preliminary Report on Patentability in International Appln. No. PCT/US2021/035285, mailed Dec. 15, 2022, 7 pages. [cited by applicant]
International Search Report and Written Opinion in International Appln. No. PCT/US2019/048881, dated Nov. 9, 2019, 16 pages. [cited by applicant]
International Search Report and Written Opinion in International Appln. No. PCT/US2019/048930, dated Nov. 20, 2019, 18 pages. [cited by applicant]
International Search Report and Written Opinion in International Appln. No. PCT/US2019/049142, dated Jun. 23, 2020, 20 pages. [cited by applicant]
International Search Report and Written Opinion in International Appln. No. PCT/US2019/049158, dated Jan. 20, 2020, 17 pages. [cited by applicant]
International Search Report and Written Opinion in International Appln. No. PCT/US2020/035598, dated Feb. 18, 2021, 12 pages. [cited by applicant]
International Search Report and Written Opinion in International Appln. No. PCT/US2020/038717, dated Oct. 16, 2020, 17 pages. [cited by applicant]
International Search Report and Written Opinion in International Appln. No. PCT/US2021/017620, dated Aug. 6, 2021, 22 pages. [cited by applicant]
International Search Report and Written Opinion in International Appln. No. PCT/US2021/017621, dated Jun. 9, 2021, 15 pages. [cited by applicant]
International Search Report and Written Opinion in International Appln. No. PCT/US2021/017714, dated Aug. 27, 2021, 22 pages. [cited by applicant]
International Search Report and Written Opinion in International Appln. No. PCT/US2021/029920, dated Oct. 6, 2021, 21 pages. [cited by applicant]
International Search Report and Written Opinion in International Appln. No. PCT/US2021/035285, dated Oct. 18, 2021, 14 pages. [cited by applicant]
International Search Report and Written Opinion in International Appln. No. PCT/US2023/065745, mailed on Jun. 26, 2023, 14 pages. [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. [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 et al., “The interaction of the antibody molecule with specific antigen,” In Immunobiology: The Immune System in Health and Disease, 5th edition, 5 pages, 2001. [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, Dec. 2, 2019, 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, Mar. 5, 2018, 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]
Klingemann et al., “Natural killer cells for immunotherapy-advantages of the NK-92 cell line over blood NK cells,” Frontiers in Immunology, Mar. 14, 2016, 7(91):1-7. [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]
Kozlowska et al., “Adoptive transfer of osteoclast-expanded natural killer cells for immunotherapy targeting cancer stem-like cells in humanized mice,” Cancer Immunology, Immunotherapy, Jul. 2016, 65:835-845. [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., “Lipid metabolism fuels cancer's spread,” Cell Metabolism, Feb. 7, 2017, 25(2):228-230. [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]
Li et al., “Transforming Growth Factor-β Regulation of Immune Responses,” Annu. Rev. Immunol., 2006, 24:99-146. [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 haemagglutinins 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 conventional T-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]
Matsuura et al., “Pole test is a useful method for evaluating the mouse movement disorder caused by striatal dopamine depletion,” Journal of Neuroscience Methods, 73(1):45-48, 1997. [cited by applicant]
Mccarron et al., “TGF-β prevents T follicular helper cell accumulation and B cell autoreactivity,” J Clin Invest., 2014, 124(10):4375-4386. [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. [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]
Mikayama et al., “Molecular cloning and functional expression of a cDNA encoding glycosylation-inhibiting factor,” Proc. Natl. Acad. Sci. USA, Nov. 1, 1993, 90(21):10056-10060. [cited by applicant]