IP Library › Granted Patent US 12,428,465
Granted Patent B2
US 12,428,465 · App. 17/365,881 · Granted Sep 30, 2025

Therapeutic peptides and methods for treating type 2 diabetes

Inventors: David H. Wagner, Jr. (Denver, CO); Martin G. Yussman (Denver, CO); Charles W. Henry (Denver, CO)
Assignee: OP-T LLC
C07K14/70575A61K38/191A61K38/08A61K38/10A61K38/1774A61K40/4215
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Quick Facts
Patent No.
US 12,428,465
App. No.
17/365,881
Granted
Sep 30, 2025
Kind
B2
Abstract

The present disclosure provides, among other things, small peptides that are capable of interacting with CD40, thereby interfering with the ability of CD40 to interact with CD154, which impacts, e.g., inflammation and atherosclerosis. The present disclosure further provides use of such peptides in the treatment of, e.g., type 2 diabetes and auto-inflammatory disease. In particular, small peptides that are capable of interacting with CD40, thereby interfering with the ability of CD40 to interact with CD154, impact inflammation and type 2 diabetes.

Claims (20)

1. A method for treating type 2 diabetes in a subject, the method comprising administering to the subject a therapeutically effective amount of a peptide of 6 amino acids in length and having an amino acid sequence of SEQ ID NO: 28 or 29.

2. The method of claim 1 , wherein the peptide binds to a CD40 protein in the subject.

3. The method of claim 2 , wherein the peptide binds to the CD40 protein with a Kd of no more than 1×10 −6 M.

4. The method of claim 1 , wherein the peptide inhibits the binding of CD40 to CD154 in the subject.

5. The method of claim 1 , wherein the peptide binds to multiple bone marrow derived cell types that express CD40 of approximately 45 kDa.

6. The method of claim 5 , wherein the bone marrow derived cell types that express CD40 of approximately 45 kDa comprise splenic CD4 + cells, CD8 + cells, and antigen presenting cells.

7. The method of claim 1 , wherein the peptide has an amino acid sequence of SEQ ID NO: 28.

8. The method of claim 1 , wherein the peptide has an amino acid sequence of SEQ ID NO: 29.

9. The method of claim 1 , wherein the subject is human.

10. The method of claim 1 , wherein the method treats glucose intolerance and/or insulin insensitivity in the subject.

11. The method of claim 1 , wherein administration of the peptide increases glucose transport protein 4 (GLUT 4) in the subject.

12. The method of claim 1 , wherein administration of the peptide reduces expression of IL-2 in the subject.

13. The method of claim 1 , wherein administration of the peptide reduces expression of IFNγ in the subject.

14. The method of claim 1 , wherein the peptide is administered in an amount sufficient to reduce or inhibit interleukin-2 signaling in the subject.

15. The method of claim 1 , wherein the peptide is administered in an amount sufficient to reduce or inhibit interleukin 17 (IL-17) signaling.

16. The method of claim 1 , wherein administration of the peptide reduces expression of IL-17A in the subject.

17. A method of increasing glucose tolerance in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a peptide of 6 amino acids in length and having an amino acid sequence of SEQ ID NO: 28 or 29.

18. A method of increasing insulin sensitivity in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a peptide of 6 amino acids in length and having an amino acid sequence of SEQ ID NO: 28 or 29.

19. A method of decreasing plasma insulin levels in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a peptide of 6 amino acids in length and having an amino acid sequence of SEQ ID NO: 28 or 29.

20. A method of increasing expression of GLUT4 in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a peptide of 6 amino acids in length and having an amino acid sequence of SEQ ID NO: 28 or 29.

Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 16, 2023
From: YUSSMAN, MARTIN GLENN; HENRY, CHARLES W.
To: OP-T LLC
Reel/Frame 065584/0207 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 16, 2023
From: WAGNER, DAVID
To: THE REGENTS OF THE UNIVERSITY OF COLORADO, A BODY CORPORATE
Reel/Frame 065584/0415 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 16, 2023
From: THE REGENTS OF THE UNIVERSITY OF COLORADO, A BODY CORPORATE
To: OP-T LLC
Reel/Frame 065584/0519 →
Continuity (4)
Continuation 16240630 · Jan 4, 2019
Continuation In Part 16184129 · Nov 8, 2018
Provisional Application 62669918 · May 10, 2018
Related Publication 20210332104A1 · Oct 28, 2021
References Cited (320)
US 4642295A · Baker · 1987 [cited by applicant]
US 6264951B1 · Armitage · 2001 [cited by applicant]
US 6319671B1 · U'ren et al. · 2001 [cited by applicant]
US 6812203B1 · Pype et al. · 2004 [cited by applicant]
US 7087573B1 · Lazarus · 2006 [cited by applicant]
US 7098322B2 · Pype et al. · 2006 [cited by applicant]
US 7189518B2 · Schonbeck et al. · 2007 [cited by applicant]
US 7601335B2 · McCutcheon et al. · 2009 [cited by applicant]
US 7741280B2 · Guichard et al. · 2010 [cited by applicant]
US 8476008B2 · Nagalla et al. · 2013 [cited by applicant]
US 9409987B2 · Toporik et al. · 2016 [cited by applicant]
US 9562088B2 · Wagner · 2017 [cited by examiner]
US 10882911B2 · Park et al. · 2021 [cited by applicant]
US 11130795B2 · Wagner · 2021 [cited by applicant]
US 11744875B2 · Wagner, Jr. · 2023 [cited by examiner]
US 11793854B2 · Wagner, Jr. et al. · 2023 [cited by applicant]
US 12048734B2 · Wagner, Jr. et al. · 2024 [cited by applicant]
US 20030078269A1 · Pearson et al. · 2003 [cited by applicant]
US 20040072750A1 · Phillips et al. · 2004 [cited by applicant]
US 20050101769A1 · Pype et al. · 2005 [cited by applicant]
US 20050202531A1 · Toporik · 2005 [cited by applicant]
US 20060234316A1 · Wagner · 2006 [cited by applicant]
US 20070041971A1 · Wagner · 2007 [cited by applicant]
US 20070243259A1 · Sung et al. · 2007 [cited by applicant]
US 20080050369A1 · Yellin et al. · 2008 [cited by applicant]
US 20080058360A1 · Schonbeck et al. · 2008 [cited by applicant]
US 20100062471A1 · Kantor et al. · 2010 [cited by applicant]
US 20100172869A1 · Masuoka · 2010 [cited by applicant]
US 20110177556A1 · Prussak et al. · 2011 [cited by applicant]
US 20110178000A1 · Freyberg et al. · 2011 [cited by applicant]
US 20110229495A1 · Wagner · 2011 [cited by applicant]
US 20120282291A1 · Berghman et al. · 2012 [cited by applicant]
US 20130203719A1 · Kalergis et al. · 2013 [cited by applicant]
US 20130209463A1 · Rotman et al. · 2013 [cited by applicant]
US 20130236495A1 · Wagner · 2013 [cited by applicant]
US 20130306034A1 · Hamedovic et al. · 2013 [cited by applicant]
US 20140044641A1 · Toporik et al. · 2014 [cited by applicant]
US 20140135684A1 · Kuo et al. · 2014 [cited by applicant]
US 20140170141A1 · Toporik et al. · 2014 [cited by applicant]
US 20150366946A1 · Vol et al. · 2015 [cited by applicant]
US 20160200823A1 · Burkly et al. · 2016 [cited by applicant]
US 20160296609A1 · Oh et al. · 2016 [cited by applicant]
US 20160347816A1 · Toporik et al. · 2016 [cited by applicant]
US 20160356771A1 · Smith et al. · 2016 [cited by applicant]
US 20170108514A1 · Wagner · 2017 [cited by applicant]
US 20170232062A1 · Rotman et al. · 2017 [cited by applicant]
US 20170306034A1 · Honczarenko et al. · 2017 [cited by applicant]
US 20170319671A1 · Faulkner et al. · 2017 [cited by applicant]
US 20170355747A1 · Wagner · 2017 [cited by applicant]
US 20180194829A1 · Toporik et al. · 2018 [cited by applicant]
US 20180194847A1 · Park et al. · 2018 [cited by applicant]
US 20190194290A1 · Wagner, Jr. et al. · 2019 [cited by applicant]
US 20190231848A1 · Rotman et al. · 2019 [cited by applicant]
US 20190263888A1 · Wagner, Jr. et al. · 2019 [cited by applicant]
US 20200072837A1 · Wagner, Jr. et al. · 2020 [cited by applicant]
US 20200297795A1 · Wagner, Jr. et al. · 2020 [cited by applicant]
US 20200326333A1 · Wagner, Jr. et al. · 2020 [cited by applicant]
US 20210008162A1 · Wagner, Jr. et al. · 2021 [cited by applicant]
US 20210332104A1 · Wagner, Jr. et al. · 2021 [cited by applicant]
US 20220000979A1 · Wagner, Jr. et al. · 2022 [cited by applicant]
US 20220106381A1 · Wagner · 2022 [cited by applicant]
US 20230101772A1 · Wagner, Jr. et al. · 2023 [cited by applicant]
US 20240115651A1 · Wagner, Jr. et al. · 2024 [cited by applicant]
WO WO1999011263A1 · 1999 [cited by applicant]
WO WO2005006949A2 · 2005 [cited by applicant]
WO WO2007090280A1 · 2007 [cited by applicant]
WO WO2008036675A2 · 2008 [cited by applicant]
WO WO2010055510A2 · 2010 [cited by applicant]
WO WO2012054584A2 · 2012 [cited by applicant]
WO WO2012154215A1 · 2012 [cited by applicant]
WO WO2015148389A2 · 2015 [cited by applicant]
WO WO2019032945A1 · 2019 [cited by applicant]
WO WO2019094581A1 · 2019 [cited by applicant]
WO WO2019136307A1 · 2019 [cited by applicant]
WO WO2020210726A1 · 2020 [cited by applicant]
WO WO2021011437A1 · 2021 [cited by applicant]
WO WO2021212013A2 · 2021 [cited by applicant]
WO WO2021231898A2 · 2021 [cited by applicant]
Nathan, Diabetes Advances in Diagnosis and Treatment. JAMA, 2015; 314(10):1052-1062. (Year: 2015). [cited by examiner]
Mach et al. “Reduction of atherosclerosis in mice by inhibition of CD40 signalling”, Nature, vol. 3694, pp. 200-203, Jul. 9, 1998. [cited by applicant]
Shi et al., “Ldlr-Deficient Mice with and Atherosclerosis-Resistant Background Develop Severe Hyperglycemia and Type 2 Diabetes on a Western-Type Diet,” Biomedicines 10(6): 12 pages (2022). [cited by applicant]
“Society commits $19.4 Million for New MS Research Projects,” National Multiple Sclerosis Society, 2013 retrieved from http://vitaminad.nositio.net/news/New_Research_Fall_2013.pdf, 28 pages. [cited by applicant]
Aarts et al., “Inhibition of CD4-TRAF6 interactions by the small molecule Inhibitor 6877002 reduces neuroinflammation,” Journal of Neuroinflammation, 14(105): 105-118 (2017). [cited by applicant]
Aarts et al., “The CD40-CD40L dyad in Experimental Autoimmune Encephalomyelitis and Multiple Sclerosis,” Chapter 2 Front. Immunol., 8(1791): 24-45 (2017). [cited by applicant]
Abdelhak et al., “Primary Progressive Multiple Sclerosis: Putting Together the Puzzle,” Frontiers in Neurology, 8:234 (2017). [cited by applicant]
Alaoui-Ismaili et al., “Design of second generation therapeutic recombinant bone morphogenetic proteins,” Cytokine & Growth Factor Reviews, 20: 501-507 (2009). [cited by applicant]
Allen et al., “Therapeutic peptidomimetic strategies for autoimmune diseases: costimulation blockade,” The Journal of Peptide Research, 65(6): 591-604 (2005). [cited by applicant]
Anderson et al., “Multiple sclerosis, seizures, and antiepileptics: role of IL-18, IDO, and melatonin,” European Journal of Neurology, 18(5): 680-685 (2011). [cited by applicant]
Angelini et al., “Analysis of HLA DP, DQ, and DR alleles in adult Italian rheumatoid arthritis patients,” Human Immunology, 34(2): 135-141 (1992). [cited by applicant]
Arbour et al., “A new clinically relevant approach to expand myelin specific T cells,” Journal of Immunological Methods, 310(1-2): 53-61 (2006). [cited by applicant]
Armitage et al., “CD40L: a multi-functional ligand,” Seminars in Immunology, 5: 401-412 (1993). [cited by applicant]
Aruffo et al., “The CD40 Ligand, gp39, is Defective in Activated T Cells from Patients with X-Linked Hyper-IgM Syndrome,” Cell, 72: 291-300 (1993). [cited by applicant]
Attwood et al., “The Babel of Bioinformatics,” Science, 290(5491): 471-473 (2000). [cited by applicant]
Bai et al., “Cerebrospinal Fluid and Blood Cytokines as Biomarkers for Multiple Sclerosis: A Systematic Review and Meta-Analysis of 226 Studies With 13,526 Multiple Sclerosis Patients,” [cited by applicant]
Baker et al., “CD40 on NOD CD4 T cells contributes to their activation and pathogenicity,” Journal of Autoimmunity, 31(4): 385-392 (2008). [cited by applicant]
Balasa et al., “CD40 Ligand-CD40 Interactions are Necessary for the Initiation of Insulitis and Diabetes in Nonobese Diabetic Mice,” The Journal of Immunology, 159: 4620-4627 (1997). [cited by applicant]
Barker et al., “Prediction of Autoantibody Positivity and Progression to Type 1 Diabetes: Diabetes Autoimmunity Study in the Young (DAISY),” Journal of Clinical Endocrinology & Metabolism, 89(8):3896-3902 (2004). [cited by applicant]
Becker et al., “CD40, an extracellular receptor for binding and uptake of Hsp70-peptide complexes,” The Journal of Cell Biology, 158(7): 1277-1285 (2002). [cited by applicant]
Bee et al., “Exploring the Dynamic Range of the Kinetic Exclusion Assay in Characterizing Antigen-Antibody Interactions,” Plos One, 7(4): e36261 (2012). [cited by applicant]
Benveniste et al., “Molecular regulation of CD40 gene expression in macrophages and microglia,” Brain, Behavior, and Immunity, 18(1): 7-12 (2004). [cited by applicant]
Bojadzic et al., “CD40-targeting KGYY15 peptides do not efficiently block the CD40-CD40L interaction,” Diabetologia, 62: 2158-2160 (2019). [cited by applicant]
Bonifacio, “Predicting Type 1 Diabetes Using Biomarkers,” Diabetes Care, 38: 989-996 (2015). [cited by applicant]
Boon et al., “Prevention of Experimental Autoimmune Encephalomyelitis in the Common Marmoset ( [cited by applicant]
Bourgeois et al., “A Role for CD40 Expression on CD8+ T cells in the Generation of CD8+ T Cell Memory,” Science, 297: 2060-2063 (2002). [cited by applicant]
Bowie et al., “Deciphering the Message in Protein Sequences: Tolerance to Amino Acid Substitutions,” Science, 247(4948): 1306-1310 (1990). [cited by applicant]
Bretscher, “The two-signal model of lympocyte activation twenty-one years later,” Immunology Today, 13(2): 74-76 (1992). [cited by applicant]
Burge et al., “The Role of a Coronary Artery Calcium Scan in Type 1 Diabetes,” Diabetes Technology & Therapeutics, 18(9): 594-603 (2016). [cited by applicant]
Burgess et al., “Possible Dissociation of the Heparin-binding and Mitogenic Activities of Heparin-binding (Acidic Fibroblast) Growth Factor-1 from Its Receptor-binding Activities by Site-directed Mutagenesis of a Single… [cited by applicant]
Buzzard et al., “Multiple Sclerosis: Basic and Clinical,” Adv. Neurobiol., 2017, 15: 211-252. [cited by applicant]
Campean et al., “CD40-CD154 expression in calcified and non-calcified coronary lesions of patients with chronic renal failure,” Atherosclerosis, 190(1): 156-166 (2007). [cited by applicant]
Carter et al., “CD40 engagement of CD4+CD40+ T cells in a neo-self antigen disease model ablates CTLA-4 expression and indirectly impacts tolerance,” European Journal of Immunology, 42: 424-435 (2012). [cited by applicant]
Ceccarelli et al., “Microglia extracellular vesicles: focus on molecular composition and biological function,” [cited by applicant]
Chatzigeorgiou et al., “Blocking CD40-TRAF6 signaling is a therapeutic target in obesity-associated insulin resistance,” PNAS, 111(7): 2686-2691 (2014). [cited by applicant]
Chen et al., “CD40/CD40L dyad in the inflammatory and immune responses in the central nervous system,” [cited by applicant]
Christensen et al., “Systemic Inflammation in Progressive Multiple Sclerosis Involves Follicular T-Helper, Th17- and Activated B-Cells and Correlates with Progression,” PLOS ONE, 8(3): e57820 (2013). [cited by applicant]
Cipollone et al., “Enhanced soluble CD40 ligand contributes to endothelial cell dysfunction in vitro and monocyte activation in patients with diabetes mellitus: effect of improved metabolic control,” Diabetologia, 48: 1… [cited by applicant]
Cooper et al., “Cutting Edge: TCR Revision Occurs in Germinal Centers,” The Journal of Immunology, 173: 6532-6536 (2004). [cited by applicant]
Davidson et al., “Co-Stimulatory Blockade in the Treatment of Murine Systemic Lupus Erythematosus,” Ann. NY Acad. Sci, 987: 188-198 (2003). [cited by applicant]
De Ramon et al., “CD154-CD40 T-cell co-stimulation pathway is a key mechanism in kidney ischemia-reperfusion injury,” Kidney International, 88: 538-549 (2015). [cited by applicant]
Deambrosis et al., “Inhibition of CD40-CD154 costimulatory pathway by a cyclic peptide targeting CD154,” J. Mol. Med., 87: 181-197 (2009). [cited by applicant]
DeGraba et al., “Efficacy of an Interdisciplinary Intensive Outpatient Program in Treating Combat-Related Traumatic Brain Injury and Psychological Health Conditions,” [cited by applicant]
Devaraj et al., “Increased Monocytic Activity and Biomarkers of Inflammation in Patients With Type 1 Diabetes,” Diabetes, 55: 774-779 (2006). [cited by applicant]
Druzd et al., “Lymphocyte Circadian Clocks Control Lymph Node Trafficking and Adaptive Immune Responses,” Immunity, 2017; 46: 120-32 [PubMed: 28087238]. [cited by applicant]
Durie et al., “Prevention of Collagen-Induced Arthritis with an Antibody to gp39, the Ligand for CD40,” Science, 261: 1328-1330 (1993). [cited by applicant]
Edwards et al., “Interleukin-6 is associated with acute concussion in military combat personnel,” [cited by applicant]
Elliott et al., “Chronic white matter lesion activity predicts clinical progression in primary progressive multiple sclerosis,” [cited by applicant]
Ellmark et al., “Modulation or the CD40-CD40 ligand interaction using human anti-CD40 single-chain antibody fragments obtained from the n-CoDeR phage display library,” Immunology, 106: 456-463 (2002). [cited by applicant]
Eshaghi et al., “Progression of regional grey matter atrophy in multiple sclerosis,” [cited by applicant]
Fan et al., “The emerging role of exosome-derived non-coding RNAs in cancer biology,” [cited by applicant]
Fanslow et al., “Recombinant CD40 Ligand Exerts Potent Biologic Effect on T Cells,” Journal of Immunology, 152: 4262-4269 (1994). [cited by applicant]
Fisniku et al., “Disability and T2 MRI lesions: a 20-year follow-up of patients with relapse onset of multiple sclerosis,” Brain, 131(3): 808-817 (2008). [cited by applicant]
Fox, “Clinical features, pathogenesis, and treatment of Sjogren's syndrome,” Current Opinion in Rheumatology, 8(5): 438-445 (1996) (Abstract Only). [cited by applicant]
Garlichs et al., “Upregulation of CD40 and CD40 ligand (CD154) in patients with moderate hypercholesterolemia,” Circulation, 104: 2395-2400 (2001). [cited by applicant]
Gerritse et al., “CD40-CD40 ligand interactions in experimental allergic encephalomyelitis and multiple sclerosis,” PNAS, 93: 2499-2504 (1996). [cited by applicant]
Girvin et al., “CD40/CD40L Interaction is Essential for the Induction of EAE in the Absence of CD28-Mediated Co-stimulation,” Journal of Autoimmunity, 18(2): 83-94 (2002). [cited by applicant]
Giuliani et al., “Minocycline attenuates T cell and microglia activity to impair cytokine production in T cell-microglia interaction,” Journal of Leukocyte Biology, 78: 135-143 (2005). [cited by applicant]
Goetzl et al., “Altered levels of plasma neuron-derived exosomes and their cargo proteins characterize acute and chronic mild traumatic brain injury,” [cited by applicant]
Goetzl et al., “Traumatic brain injury increases plasma astrocyte-derived exosome levels of neurotoxic complement proteins,” [cited by applicant]
Goodnow, “Pathways for self-tolerance and the treatment of autoimmune diseases,” Lancet, 357: 2115-2121 (2001). [cited by applicant]
Goverman et al., “Transgenic mice that express a myelin basic protein-specific T cell receptor develop spontaneous autoimmunity,” Cell, 72(4): 3018-3027 (1993). [cited by applicant]
Graber et al., “Interleukin-17 in transverse myelitis and multiple sclerosis,” Journal of Neuroimmunology, 196(1-2): 124-132 (2008). [cited by applicant]
Grabstein, “The Regulation or T Cell-Dependent Antibody Formation in Vitro by CD40 Liqand and IL-2,” The Journal of Immunology, 150(8): 3141-3147 (1993). [cited by applicant]
Grossman, “Avoiding Tolerance Against Prostatic Antigens With Subdominant Peptide Epitopes,” Journal of Immunotherapy, 23(3): 237-241 (2001). [cited by applicant]
Guo et al., “CD40L-Dependant Pathway is Active at Various Stages of Rheumatoid Arthritis Disease Progression,” The Journal of Immunology, 198: 4490-4501 (2017). [cited by applicant]
Guo et al., “Protein tolerance to random amino acid change,” PNAS, 101(25): 9205-9210 (2004). [cited by applicant]
Hafler et al., “Risk alleles for multiple sclerosis identified by a genomewide study,” New England Journal of Medicine, 357(9): 851-862 (2007). [cited by applicant]
Hamlett et al., “Neuronal exosomes reveal Alzheimer's disease biomarkers in Down syndrome,” [cited by applicant]
Harrington et al., “Differential tolerance is induced in T cells recognizing distinct epitopes of myelin basic protein,” Immunity, 8(5): 571-580 (1998). [cited by applicant]
Hart et al., “Preclinical assessment of therapeutic antibodies against human CD40 and human interleukin-12/23p40 in a nonhuman primate model of multiple sclerosis,” [cited by applicant]
Hartung et al., “Diagnosis of multiple sclerosis: revisions of the McDonald criteria 2017—continuity and change,” [cited by applicant]
Heath et al., “Monoclonal antibodies to murine CD40 define two distinct functional epitopes,” Eur. J. Immunol., 24: 1828-1834 (1994). [cited by applicant]
Hemmer et al., “New concepts in the immunopathogenesis of multiple sclerosis,” Nature Reviews Neuroscience, 3(4): 291-301 (2002). [cited by applicant]
Hernandez et al., “CD40-CD40 Ligand Interaction between Dendritic Cells and CDS+ T Celis is Needed to Stimulate Maximal T Cell Responses in the Absence of CD4+ T Cell Help,” The Journal of Immunology, 178: 2844-2852 (20… [cited by applicant]
Hoffjan et al., “The genetics of multiple sclerosis: an update 2010,” Molecular and Cellular Probes, 24(5): 237-243 (2010). [cited by applicant]
Homann et al., “CD40L Blockade Prevents Autoimmune Diabetes by Induction of Bitypic NK/DC Reaulatorv Geils,” Immunity, 16: 403-415 (2002). [cited by applicant]
Howard et al., “Immunotherapy Targeting the CD40/CD154 Costimulatory Pathway for Treatment of Autoimmune Disease,” Autoimmunity, 37(5): 411-418 (2004). [cited by applicant]
Huseby et al., “A pathogenic role for myelin-specific CD8+ T cells in a model for multiple sclerosis,” Journal of Experimental Medicine, 194(5): 669-676 (2001). [cited by applicant]
Ichikawa et al., “Increased Fas antigen on T cells in multiple sclerosis,” Journal of Neuroimmunology, 71(1-2): 125-129 (1996). [cited by applicant]
Iezzi et al., “CD40-CD40L cross-talk integrates strong antigenic signals and microbial stimuli to induce development of IL-17-producing CD4+ T cells,” Proc Natl Acad Sci USA, 106: 876-881 (2009). [cited by applicant]
Ilonen et al., “Abnormalities within CD4 and CD8 T lymphocyte subsets in type 1 (insulin-dependent) diabetes,” Clin. exp. Immunol., 85(2): 278-281 (1991). [cited by applicant]
Jensen et al., “Increased T cell expression of CD154 (CD40-ligand) in multiple sclerosis,” European Journal of Neurology, 8: 321-328 (2001). [cited by applicant]
Kalatha et al., “Glial and neuroaxonal biomarkers in a multiple sclerosis (MS) cohort,” [cited by applicant]
Karpusas et al., “2 .ANG. crystal structure of an extracellular fragment of human CD40 ligand,” Structure, 3,(10): 1031-1039 (1995). [cited by applicant]
Kennedy et al., “Acute Exercise Induces GLUT4 Translocation in Skeletal Muscle of Normal Human Subjects and Subjects With Type 2 Diabetes,” Diabetes, 48: 1-6 (1999). [cited by applicant]
Kent et al., “Expanded T cells from pancreatic lymph nodes of type 1 diabetic subjects recognize an insulin epitope,” Nature, 435(7039): 224-228 (2005). [cited by applicant]
Khambhati et al., “Immunotherapy for the prevention of atherosclerotic cardiovascular disease: Promise and possibilities,” Atherosclerosis 276: 1-9 (2018). [cited by applicant]
Khan et al., “Differential peptide binding to CD40 evokes counteractive responses,” Human Immunology, 73: 465-469 (2012). [cited by applicant]
King et al., “The Use of Animal Models in Diabetes Research,” British Journal of Pharmacology, 166: 877-894 (2012). [cited by applicant]
Kitagawa et al., “Identification of three novel peptides that inhibit CD40-CD154 interaction,” Mod. Rheumatol, 15: 423-426 (2005). [cited by applicant]
Kobata et al., “Role of costimulatory molecules in autoimmunity,” Reviews in Immunogenetics, 2: 74-80 (2000). [cited by applicant]
Kuo et al., “IL-17 and CD40 ligand synergistically stimulate the chronicity of diabetic nephropathy,” Nephrol Dial Transplant, 33: 248-256 (2018). [cited by applicant]
Kutzelnigg et al., “Cortical demyelination and diffuse white matter injury in multiple sclerosis,” [cited by applicant]
Laemmli ., “Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4,” Nature, 227: 680-685 (1970). [cited by applicant]
Laman et al., “Protection of marmoset monkeys against EAE by treatment with a murine antibody blocking CD40 (mu5D12),” Eur. J. Immunol., 32: 2218-2228 (2002). [cited by applicant]
Laman et al., “Therapy with antibodies against CD40L (CD154) and CD44-variant isoforms reduces experimental autoimmune encephalomyelitis induced by a proteolipid protein peptide,” Multiple Sclerosis, 4: 147-153 (1998). [cited by applicant]
Lederman et al., “Identification of a Novel Surface Protein on Activated CD4+ T Cells That Induces Contact-dependant B Cell Differentiation (Help),” J. Exp. Med., 175: 1091-1101 (1992). [cited by applicant]
Lederman et al., “Molecular Interactions Mediating T-B Lymphocyte Collaboration in Human Lymphoid Follicies: Roles of T Cell-B Cell-Activating Molecule (5c8 Antigen) and CD40 in Contact-Dependent Help,” The Journal of I… [cited by applicant]
Ledreux et al., “Assessment of Long-Term Effects of Sports-Related Concussions: Biological Mechanisms and Exosomal Biomarkers,” [cited by applicant]
Ledreux et al., “Small Neuron-Derived Extracellular Vesicles from Individuals with Down Syndrome Propagate Tau Pathology in the Wildtype Mouse Brain,” [cited by applicant]
Lee et al., “Mouse models of atherosclerosis: a historical perspective and recent advances,” Lipids in Health and Disease, 16: 1-11 (2017). [cited by applicant]
Liu et al., “CD127 expression inversely correlates with FoxP3 and suppressive function of human CD4+T reg cells,” Journal of Experimental Medicine, 203(7): 1701-1711 (2006). [cited by applicant]
Liu et al., “NG2 glia are required for maintaining microglia homeostatic state,” [cited by applicant]
Liu et al., “Targeted exosome-mediated delivery of opioid receptor Mu siRNA for the treatment of morphine relapse,” [cited by applicant]
Lovett-Racke et al., “Decreased dependence of myelin basic protein-reactive T cells on CD28-mediated costimulation in multiple sclerosis patients,” Journal of Clincial Investigation, 101(4): 725-730 (1998). [cited by applicant]
Lucchinetti et al., “Inflammatory Cortical Demyelination in Early Multiple Sclerosis,” New England Journal of Medicine, 365(23): 2188-2197 (2011). [cited by applicant]
Lutgens et al., “Long-term reversal of hypercholesterolemia in low density lipoprotein receptor (LDLR)-deficient mice by adenovirus-mediated LDLR gene transfer combined with CD154 blockade,” Nature Medicine, 5: 1313-131… [cited by applicant]
Lutterotti et al., “Antigen-specific tolerance by autologous myelin peptide-coupled cells: a phase 1 trial in multiple sclerosis,” Science Translational Medicine, 5(188) 20 pages (2013). [cited by applicant]
Macaron et al., “Diagnosis and Management of Progressive Multiple Sclerosis,” [cited by applicant]
Mackey et al., “Calcifications, arterial stiffness, and atherosclerosis,” Atherosclerosis, Large Arteries and Cardiovascular Risk. Adv Cardiol., 44: 234-244 (2008). [cited by applicant]
Maggi et al., “Chronic White Matter Inflammation and Serum Neurofilament Levels in Multiple Sclerosis,” [cited by applicant]
Marsh, “Nomenclature for factors of the HLA system, updated Jan. 2012,” Human Immunology, 73: 593-596 (2012). [cited by applicant]
Mayo Clinic Diabetes, mayoclinic.org/diseases-conditions/diabetes/symptoms-causes/syc-2037 1444?; pp. 1-7; mayoclinic.org/diseases-conditions/diabetes/diagnosis-treatment/drc-20371451?p=1; pp. 1-1 1, downloaded Feb. 20,… [cited by applicant]
Mayo Clinic: Arteriosclerosis / Athersclerosis, mayoclinic.org/diseases-conditions/arteriosclerosis atherosclerosis/symptoms-causes /syc-20350569?, pp. 1-4; mayoclinic.org/diseases-conditions/arteriosclerosis- atheroscl… [cited by applicant]
McMahon et al., “Epitope spreading initiates in the CNS in two mouse models of multiple sclerosis,” Nature Medicine, 11(3): 335-339 (2005). [cited by applicant]
Mcwhirter et al., “Crystallographic analysis of CD40 recognition and signaling by human TRAF2,” Proc. Natl. Acad. Sci. USA, 96: 8408-8413 (1999). [cited by applicant]
Miller et al., “Antigen presentation in the CNS by myeloid dendritic cells drives progression of relapsing experimental autoimmune encephalomyelitis,” Annals of the New York Academy of Sciences, 1103: 179-191 (2007). [cited by applicant]
Miller et al., “Clinically isolated syndromes,” Lancet Neurology, 11(2): 157-169 (2012). [cited by applicant]
Miller et al., “The role of magnetic resonance techniques in understanding and managing multiple sclerosis,” Brain, 121: 3-24 (1998). [cited by applicant]
Miller et al., “Virus-induced autoimmunity: epitope spreading to myelin autoepitopes in Theiler's virus infection of the central nervous system,” Advances in Virus Research, 56: 199-217 (2001). [cited by applicant]
Munroe et al., “Pro-Inflammatory⋅ Adaptive Cytokines and Shed Tumor Necrosis Factor Receptors are Elevated Preceding Systemic Lupus Erythematosus Disease Flare,” Arthritis Rheumatol., 66(7): 1888-1899 (2014). [cited by applicant]
Najafian et al., “T cell costimulatory pathways: blockade for autoimmunity,” [cited by applicant]
Nguyen et al., “CD+CD40+ T cell levels predict risk of developing type I diabetes pre-diabetics,” J Invest Med, Abstract, 62(1): 151-152 (2014). [cited by applicant]
Nyakeriga et al., “TCR-induced T cell activation leads to simultaneous phosphorylation at Y505 and Y394 of p56(1ck) residues,” Cytometry A, 81(9): 797-805 (2012). [cited by applicant]
O'Connor et al., “Antibodies from inflamed central nervous system tissue recognize myelin oligodendrocyte glycoprotein,” Journal of Immunology, 175(3): 1974-1982 (2005). [cited by applicant]
Ontaneda., “Progressive Multiple Sclerosis,” [cited by applicant]
Pawson et al., “Assembly of Cell Regulatory Systems Through Protein Interaction Domains,” Science, 300: 445-452 (2003). [cited by applicant]
Peng et al., “Microglia-Derived Exosomes Improve Spinal Cord Functional Recovery after Injury via Inhibiting Oxidative Stress and Promoting the Survival and Function of Endothelia Cells,” [cited by applicant]
Poggi et al., “The inflammatory receptor CD40 is expressed on human adipocytes: contribution to crosstalk between lymphocytes and adipocytes,” Diabetologia, 52: 1152-1163 (2009). [cited by applicant]
Polman et al., “Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria,” Annals of Neurology, 69(2): 292-302 (2011). [cited by applicant]
Polman et al., “Drug treatment of multiple sclerosis,” Medicine Cabinent, 173: 398-402 (2000). [cited by applicant]
Polman et al., “Multiple sclerosis diagnostic criteria: three years later,” Multiple Sclerosis Journal, 11(1): 5-12 (2005). [cited by applicant]
Pullen et al., “CD40 Signaling through Tumor Necrosis Factor Receptor-associated Factors (TRAFs),” The Journal of Biological Chemistry, 274(20): 14246-14254 (1999). [cited by applicant]
Pulliam et al., “Plasma neuronal exosomes serve as biomarkers of cognitive impairment in HIV infection and Alzheimer's disease,” [cited by applicant]
Quezada et al., “Distinct Mechanisms of Action of Anti-CD154 in Early Versus Late Treatment of Murine Lupus Nephritis,” Arthritis & Rheumatism, 48(9): 2541-2554 (2003). [cited by applicant]
Ramsdell et al., “CD40 Ligand Acts as a Costimulatory Signal for Neonatal Thymic Gamma Delta T Cells,” The Journal of Immunology, 152: 2190-2197 (1994). [cited by applicant]
Resetkova et al., “Antibody to gp39, the Ligand for CD40 Significantly Inhibits the Humoral Response from Graves' Thyroid Tissues Xenografted into Severe Combined Immunodeficient (SCID) Mice,” Thyroid, 6(4): 267-273 (19… [cited by applicant]
Richards et al., “A peptide containing a novel FPGN CD40-binding sequence enhances adenoviral infection of murine and human dendritic cells,” Eur. J. Biochem., 270: 2287-2294 (2003). [cited by applicant]
Rolink et al., “The SCID but Not the RAG-2 Gene Product is Required for S?- S? Heavy Chain Class Switching,” Immunity, 5(4): 319-330 (1996). [cited by applicant]
Rosetti et al., “The many faces of Mac-1 in autoimmune disease,” Immunological Reviews, 269: 175-193 (2016). [cited by applicant]
Ruiz et al., “Resolution of inflammation during multiple sclerosis,” [cited by applicant]
Russo et al., “Platelet-Activating Factor Mediates CD40-Dependent Angiogenesis and Endothelial-Smooth Muscle Cell Interaction,” The Journal of Immunology, 5489-5497 (2003). [cited by applicant]
Santilli et al., “CD40/CD40L system and vascular disease,” [cited by applicant]
Sarawar et al., “Stimulation via CD40 can substitute for CD4 T cell function in preventing reactivation of latent herpesvirus,” PNAS, 98: 6325-6329 (2001). [cited by applicant]
Sawcer et al., “Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis,” Nature, 476(7359): 214-219 (2011). [cited by applicant]
Sawcer, “The complex genetics of multiple sclerosis: pitfalls and prospects,” Brain, 131: 3118-3131 (2008). [cited by applicant]
Schonbeck et al., “Molecules in focus, CD154 (CD40 ligand),” The International Journal of Biochemistry & Cell Biology 32: 687-693 (2000). [cited by applicant]
Schonbeck et al., “The CD40/CD154 receptor/ligand dyad,” CMLS—Cellular and Molecular Life Sciences, 58: 4-43 (2001). [cited by applicant]
Schuh et al., “Features of Human CD3+CD20+ T Cells,” [cited by applicant]
Seijkens et al., “CD40-CD40L: linking pancreatic, adipose tissue and vascular inflammation in type 2 diabetes and its complications,” Diab Vasc Dis Res, 10: 115-122 (2012). [cited by applicant]
Seko et al., “Expression of Tumor Necrosis Factor (TNF) Receptor/Ligand Superfamily Co-Stimulatory Molecules CD40, CD30L, CD27L, and Ox40L in Murine Hearts with Chronic Ongoing Myocarditis Caused by Coxsackie Virus B3,”… [cited by applicant]
Sharma et al., “Glioma-derived exosomes drive the differentiation of neural stem cells to astrocytes,” [cited by applicant]
Siebert et al., “An analytical workflow for investigating cytokine profiles,” Cytometry A, 73(4): 289-298 (2008). [cited by applicant]
Siracusa et al., “Astrocytes: Role and Functions in Brain Pathologies,” [cited by applicant]
Skolnick et al., “From genes to protein structure and function: novel applications of computational approaches in the genomic era,” Trends in Biotech, 18: 34-39 (2000). [cited by applicant]
Smith et al., “Multi-peptide coupled-cell tolerance ameliorates ongoing relapsing EAE associated with multiple pathogenic autoreactivities,” Journal of Autoimmunity, 27(4): 218-231 (2007). [cited by applicant]
Steck et al., “Genetics of type 1 cliabetes,” Clinical Chemistry, 57(2): 176-185 (2011). [cited by applicant]
Stein et al., “Long-term reversal of hypercholesterolemia in low density lipoprotein receptor (LDLR)-deficient mice by adenovirus-mediated LDLR gene transfer combined with CD154 blockade,” The Journal of Gene Medicine, … [cited by applicant]
Stumpf et al., “Enhanced levels or CD154 (CD40 ligand) on platelets in patients with chronic heart failure,” The European Journal of Heart Failure, 5: 629-637 (2003). [cited by applicant]
Stys et al., “Recent advances in understanding multiple sclerosis,” [cited by applicant]
Sun et al., “Characterization and Biomarker Analyses of Post-COVID-19 Complications and Neurological Manifestations,” [cited by applicant]
Sun et al., “Co-stimulation agonists as a new immunotherapy for autoimmune diseases,” TRENDS in Molecular Medicine, 9(11): 483-489 (2003). [cited by applicant]
Takada et al., “Integrin Binding to the Trimeric Interface of CD40L Plays a Critical Role in CD40/CD40L Signaling,” J. Immunol., 203: 1383-1391 (2019). [cited by applicant]
Takahashi et al., “The role of extracellular vesicle microRNAs in cancer biology,” [cited by applicant]
Takeda et al., “Neuronal Differentiation of Human Mesenchymal Stem Cells Using Exosomes Derived from Differentiating Neuronal Cells,” [cited by applicant]
Thorsby et al., “Particular HLA-DQ molecules play a dominant role in determining susceptibility or resistance to Type 1 (insulin-dependent) diabetes mellitus,” Diabetologia, 36(5): 371-377 (1993)(Abstract Only). [cited by applicant]
Thouvenot., “Update on clinically isolated syndrome,” Presse Med., 2015, 44(4 Pt 2): e121-136. [cited by applicant]
Toubi et al., “The Role of CD40-CD154 Interactions in Autoimmunity and the Benefit of Disrupting this Pathway,” Autoimmunity, 37: 457-464 (2004). [cited by applicant]
Townsend et al., “CD40 signaling regulates innate and adaptive activation of microglia in response to amyloid b-peptide,” Eur. J. Immunol., 35: 901-910 (2005). [cited by applicant]
Vaitaitis et al, “Cutting Edge: CD40-Induced Expression of Recombination Activating Gene (RAG) 1 and RAG2: A Mechanism for the Generation of Autoaggressive T Cells in the Periphery,” The Journal of Immunology, 170: 3455… [cited by applicant]
Vaitaitis et al., “A CD40 targeting peptide prevents severe symptoms in experimental autoimmune encephalomyelitis,” [cited by applicant]
Vaitaitis et al., “A CD40-targeted peptide controls and reverses type 1 diabetes in NOD mice,” Diabetologia, 57: 2366-2373 (2014). [cited by applicant]
Vaitaitis et al., “An Alternative Role for Foxp3 as an Effector T Cell Regulator Controlled through CD40,” The Journal of Immunology, 191: 717-725 (2013). [cited by applicant]
Vaitaitis et al., “Biomarker discovery in pre-Type 1 Diabetes; Th40 cells as a predictive risk factor,” [cited by applicant]
Vaitaitis et al., “CD40 glycoforms and TNF-receptors 1 and 2 in the formation of CD40 receptor(s) in autoimmunity,” Molecular Immunology, 47: 2303-2313 (2010). [cited by applicant]
Vaitaitis et al., “CD40 interacts directly with RAG1 and RAG2 in autoaggressive T cells and Fas prevents CD40 induced RAG expression,” Cellular and Molecular Immunology, 10(6): 483-489 (2013). [cited by applicant]
Vaitaitis et al., “CD40-mediated signalling influences trafficking, T-cell receptor expression, and T-cell pathogenesis, in the NOD model of type 1 diabetes,” Immunology, 152: 243-254 (2017). [cited by applicant]
Vaitaitis et al., “CD40-targeted peptide proposed for type 1 diabetes therapy lacks relevant binding affinity to its cognate receptor Reply to Pagni PP, Wolf A, Lo Conte M et al [letter],” Diabetologia, 62: 1730-1731 (2… [cited by applicant]
Vaitaitis et al., “Galectin-9 Controls CD40 Signaling through a Time Independent Mechanism and Redirects the Cytokine Profile of Pathogenic T Cells in Autoimmunity,” PLoS ONE, 7(6): e38708:1-13 (2012). [cited by applicant]
Vaitaitis et al., “High Distribution of CD40 and TRAF2 in TMO T Cell Rafts Leads to Preferential Survival of this Auto-Aggressive Population in Autoimmunity,” PLoS ONE, 3(4): e2076: 1-11 (2008). [cited by applicant]
Vaitaitis et al., “Th40 cells (CD4+CD40+ Tcells) drive a more severe form of Experimental Autoimmune Encephalomyelitis than conventional CD4 T cells,” PLoS ONE, 12: e0172037 pp. 1-24 (2017). [cited by applicant]
Vaitaitis et al., “The Expanding Role of TNF-Receptor Super Family Member CD40 (tnfrsf5) in Autoimmune Disease: Focus on Th40 Cells,” Current Immunology Reviews, 6(2): 130-136 (2010). [cited by applicant]
Van Kooten et al., “CD40-CD40 ligand,” [cited by applicant]
Varo et al., “Soluble CD40L—Risk Prediction After Acute Coronary Syndromes,” Circulation, 108: 1049-1052 (2003). [cited by applicant]
Vaz et al., “Phenotypic Effects of Wild-Type and Mutant SOD1 Expression in N9 Murine Microglia at Steady State, Inflammatory and Immunomodulatory Conditions,” [cited by applicant]
Verma et al., “Not Just an Adhesion Molecule: LFA-1 Contact Tunes the T Lymphocyte Program,” The Journal of Immunology, 199: 1213-1221 (2017). [cited by applicant]
Wagner et al., “Expression of CD40 identifies a unique pathogenic T cell population in type 1 diabetes,” PNAS, 99(6): 3782-3787 (2002). [cited by applicant]
Wagner et al., “Increased expression of CD40 on thymocytes and peripheral T cells in autoimmunity: A mechanism for acquiring changes in the peripheral T cell receptor repertoire,” International Journal of Molecular Medi… [cited by applicant]
Waid et al., “A unique T cell subset described as CD4loCD40+ T cells (TCD40) in human type 1 diabetes,” Clinical Immunology, 124: 138-148 (2007). [cited by applicant]
Waid et al., “A unique T cell subset, Th40, are pathogenic and diagnostic in mulitple sclerosis,” Journal of Immunology, 186(1): Meeting Abstract (2011). [cited by applicant]
Waid et al., “Defining a New Biomarker for the Autoimmune Component of Multiple Sclerosis: Th40 cells,” J. Neuroimmunol., 270: 75-85 (2014). [cited by applicant]
Waid et al., “Disruption of the homeostatic balance between autoaggressive (CD4+CD40+) and regulatory (CD4+CD25+FoxP3+) T cells promotes diabetes,” Journal of Leukocyte Biology, 84: 431-439 (2008). [cited by applicant]
Waid et al., “Peripheral CD4loCD40+ auto-aggressive T cell expansion during insulin-dependent diabetes mellitus,” Eur. J. Immunol, 34: 1488-1497 (2004). [cited by applicant]
Walling et al., “LFA-1 in T Cell Migration and Differentiation,” Frontiers in Immunology, 9: Article 952 (2018). [cited by applicant]
Winer et al., “B Lymphocytes promote insulin resistance through modulation of T Lymphocytes and production of pathogenic IgG antibody,” Nat Med, 17: 610-617 (2011). [cited by applicant]
Winston et al., “Assessing Neuronal and Astrocyte Derived Exosomes From Individuals With Mild Traumatic Brain Injury for Markers of Neurodegeneration and Cytotoxic Activity,” [cited by applicant]
Wucherpfennig et al., “A Review of T-Cell Receptors in Multiple Sclerosis: Clonal Expansion and Persistence of Human T-Cells Specific for an Immunodominant Myelin Basic Protein Peptidea,” Annals of the New York Academy … [cited by applicant]
Yu et al., “Reduced oligodendrocyte exosome secretion in multiple system atrophy involves SNARE dysfunction,” [cited by applicant]
Yu et al., “Targeting CD40 with a Selective Phage Display Derived Peptide,” pp. 61-74. [cited by applicant]
Zhang et al., “T cell and antibody responses in remitting-relapsing experimental autoimmune encephalomyelitis in (C57BL/6 x SJL) F1 mice,” Journal of Neuroimmunology, 148(1-2): 1-10 (2004). [cited by applicant]
Zhang et al., “The regulation of integrin function by divalent cations,” Cell Adhesion & Migration, 6(1): 20-29 (2012). [cited by applicant]
Amer. Diabetes Association Diagnosis and Classification of Diabetes Mellitus, Diabetes Care, 2014, 37, Suppl.I :S8 I-S90. [cited by applicant]
Bak et al., “Physicochemical and Formulation Developability Assessment for Therapeutic Peptide Delivery—A Primer,” The AAPS Journal, 17(1): 144-155 (2015). [cited by applicant]
Biosyn., “Why acetylate and amidate a peptide,” accessed on Mar. 22, 2021 at <https://biosyn.com/faq/why-acetylate-and-amidate-apeptide.aspx>: 1 page (2008). [cited by applicant]
Catchpole et al., “Canine diabetes mellitus: can old dogs teach us new tricks?,” Diabetologia, 48: 1948-1956 (2005). [cited by applicant]
Gottlieb et al., “Managing feline diabetes: current perspectives,” Vet Med (Auckl), 9: 33-42 (2018). [cited by applicant]
Grant application entitled “Developing a small peptide to control autoimmune inflammation in type 1 diabetes” by PI: David H, Wagner and received on Sep. 2, 2016 and publicly available on Jan. 5, 2018, p. 1-46 (2018). [cited by applicant]
Grossman, “Avoiding Tolerance Against Prostatic Antigens With Subdominant Peptide Epitopes,” Journal of Immunotherapy, 24(3): 237-241 (2001). [cited by applicant]
Hancock., “Preventing and managing diabetes: an exemplar for NCDS,” C3 Collaborating for Health: pp. 1-8 (2012). [cited by applicant]
Harigai, “Involvement of CD40-D154 interaction in immunopathogenesis of collagen diseases and its application to a novel therapeutic strategy”, Jpn. J. Clin. Imnunol., 27 (6) 379-388 (2004). [cited by applicant]
Huang et al., Resolving the Conundrum of Islet Transplantation by Linking Metabolic Dysregulation, Inflammation, and Immune Regulation, Endocrine Reviews, 29(5): 603-630 (2008). [cited by applicant]
Johnson et al., “Diabetes, Insulin Resistance, and Metabolic Syndrome in Horses,” J Diabetes Sci Technol, 6(3): 534-540 (2012). [cited by applicant]
Leighton et al., “A Practical Review of C-Peptide Testing in Diabetes,” Diabetes Ther, 8(3): 475-487 (2017). [cited by applicant]
Matthews et al., “Utility of murine models for the study of spontaneous autoimmune type 1 diabetes,” Pediatric Diabetes, 6: 165-177 (2005). [cited by applicant]
Nelson et al., “Classification and etiology of diabetes in dogs and cats,” Thematic Review, T1-T9 (2014). [cited by applicant]
O'Kell et al., “Comparative Pathogenesis of Autoimmune Diabetes in Humans, NOD Mice, and Canines: Has a Valuable Animal Model of Type 1 Diabetes Been Overlooked?,” Diabetes, 66(7): 1443-1452 (2017). [cited by applicant]
Partial Supplementary European Search Report for EP Application No. EP 20840056.4 dated Mar. 23, 2023. [cited by applicant]
Patel et al., “Recent developments in protein and peptide parenteral delivery approaches,” Ther. Deliv., 5(3): 337-365 (2014). [cited by applicant]
Poggi et al., “OP 27 New pathways involved in the cross talk between immune cells and metabolic tissues” Diabelologia 55:[Suppll JS1-S538 (2012). [cited by applicant]
Pullen et al., “CD40 Signaling through Tumor Necrosis Factor Receptor-associated Factors (TRAFs): Binding Site Specificity and Activation of Downstream Pathways by Distinct TRAFs,” J Biol Chem, 274(20): 14246-14254 (199… [cited by applicant]
Shukshith et al., “Water for Pharmaceutical Use,” Int. J. Pharm. Sci. Rev. Res., 36(1): 199-204 (2016). [cited by applicant]
Vaitaitis, G.M. et al.—2012—PlosOne—vol. 7, e38708, p. 1-13. [cited by applicant]
Wang et al., “Parenteral Formulations of Proteins and Peptides: Stability and Stabilizers,” Journal of Parenteral Science and Technology, 42(2S): S3-S25 (1988). [cited by applicant]
Wikipedia, “Phosphate-buffered saline,” <https://en.wikipedia.org/wiki/Phosphate-buffered saline>: Accessed on Mar. 25, 2022 (Year: 2022). [cited by applicant]
Balla et al., “Iron Homeostasis in chronic inflammation” Acta Physiolgica Hungarica, vol. 94, Issue 1-2, pp. 95-106 (2007). [cited by applicant]
Barichello et al., “Biomarkers for sepsis: more than just fever and leukocytosis—a narrative review” Critical Care, 26:14 (2022). [cited by applicant]
Barichello et al., “Neurochemical effects of sepsis on the brain” Clinical Science, vol. 137, p. 401-414 (2023). [cited by applicant]
Barichello et al., “The blood-brain barrier dysfunction in sepsis” Tissue Barriers, vol. 9, No. 1. (2021). [cited by applicant]
Chew et al., “Soluble CD40L (CD154) is increased in patients with shock” Inflammation Research, vol. 59, p. 979-982 (2010). [cited by applicant]
Extended European Search Report for EP Application No. 23181309.8 dated Sep. 19, 2023. [cited by applicant]
Gambichler et al., “Prognostic Performance of Inflammatory Biomarkers Based on Complete Blood Counts in COVID-19 Patients” Viruses, vol. 15 (2023). [cited by applicant]
Hager et al., “Affinity and Epitope Profiling of Mouse Anti?CD40 Monoclonal Antibodies”, Scandinavian journal of immunology 57.6: 517-524 (2003). [cited by applicant]
Hao et al., “Increased inflammatory mediators levels are associated with clinical outcomes and prolonged illness in severe COVID-19 patients” International Immunopharmacology, vol. 123 (2023). [cited by applicant]
Liu et al., “CD11b is a Novel Alternate Receptor for CD154 during Alloimmunity” Am J Transplant, vol. 20, No. 8, p. 2216-2225 (2020). [cited by applicant]
Matsumoto et al., “The clinical importance of a cytokine network in the acute phase of sepsis” Scientific Reports, vol. 8 (2018). [cited by applicant]
Michels et al., “CD40-CD40 Ligand Pathway Is a Major Component of Acute Neuroinflammation and Contributes to Long-term Cognitive Dysfunction after Sepsis” Molecular Medicine, vol. 21 (2015). [cited by applicant]
Nolan et al., “CD40 but Not CD154 Knockout Mice Have Reduced Inflammatory Response in Polymicrobial Sepsis: A Potential Role for [cited by applicant]
Sekino et al., “Sepsis-associated brain injury: underlying mechanisms and potential therapeutic strategies for acute and long-term cognitive impairments” Journal of Neuroinflammation, vol. 19 (2022). [cited by applicant]
Tang et al., “Molecular basis and therapeutic implications of CD40/CD40L immune checkpoint” Pharmacol Ther, vol. 219 (2021). [cited by applicant]
Urbanski et al., “Serum ferritin/C-reactive protein ratio is a simple and effective biomarker for diagnosing iron deficiency in the context of systemic inflammation” QJM: An International Journal of Medicine (2023). [cited by applicant]
Yao et al., “Neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and systemic immune inflammation index (SII) to predict postoperative pneumonia in elderly hip fracture patients” Journal of Orthopa… [cited by applicant]