Granted Patent
B2
US 12,492,245 · App. 17/870,593 · Granted Dec 9, 2025
Anti-CCL8 antibodies and treatment of lung injury by CCL8 inhibition
Inventors:
Hippokratis Kiaris (Irmo, SC); Ioulia Chatzistamou (Irmo, SC); Asieh Naderi (Columbia, SC); Bernardo Chavez (Columbia, SC)
Assignee:
UNIVERSITY OF SOUTH CAROLINA
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Abstract
Methods for treating lung injury by administration of an anti-CCL8 antibody are disclosed. Also disclosed are methods for evaluating lung therapies by use of an animal model of the genus Peromyscus.
Claims (4)
1 . A method for treating a subject diagnosed with acute respiratory distress syndrome or a severe acute respiratory syndrome (SARS) associated coronavirus infection comprising administering an anti-CCL8 antibody or antigen binding fragment thereof to pulmonary tissue of the subject, wherein the anti-CCL8 antibody or antigen binding fragment thereof includes SEQ ID NO: 4 and SEQ ID NO: 12 or includes SEQ ID NO: 4 and SEQ ID NO: 20.
2 . The method of claim 1 , wherein the antibody is a monoclonal antibody.
3 . The method of claim 1 , wherein the antibody or antigen binding fragment thereof is an antigen binding fragment that comprises a Fab, a Fab′, a F(ab′)2, a Fv, a disulfide linked Fv, or a scFv.
4 . The method of claim 1 , wherein the anti-CCL8 antibody or antigen binding fragment thereof is administered in an amount of between 1 ng/kg body weight/day and 100 mg/kg body weight/day.
Assignments (2)
CONFIRMATORY LICENSE
Recorded Feb 3, 2025
From: UNIVERSITY OF SOUTH CAROLINA
To: NATIONAL SCIENCE FOUNDATION
Reel/Frame 070084/0481 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded May 3, 2023
From: KIARIS, HIPPOKRATIS; CHATZISTAMOU, IOULIA; NADERI, ASIEH; CHAVEZ, BERNARDO
To: UNIVERSITY OF SOUTH CAROLINA
Reel/Frame 063521/0598 →
Continuity (2)
Provisional Application
63246423
· Sep 21, 2021
References Cited (129)
US 4522811A
· Eppstein et al.
· 1985
[cited by applicant]
US 4868116A
· Morgan et al.
· 1989
[cited by applicant]
US 4980286A
· Morgan et al.
· 1990
[cited by applicant]
US 5135917A
· Burch
· 1992
[cited by applicant]
US 5168053A
· Altman et al.
· 1992
[cited by applicant]
US 5176996A
· Hogan et al.
· 1993
[cited by applicant]
US 5334711A
· Sproat et al.
· 1994
[cited by applicant]
US 5476766A
· Gold et al.
· 1995
[cited by applicant]
US 5543293A
· Gold et al.
· 1996
[cited by applicant]
US 5580967A
· Joyce
· 1996
[cited by applicant]
US 5595873A
· Joyce
· 1997
[cited by applicant]
US 5624824A
· Yuan et al.
· 1997
[cited by applicant]
US 5631115A
· Ohtsuka et al.
· 1997
[cited by applicant]
US 5646042A
· Stinchcomb et al.
· 1997
[cited by applicant]
US 5652107A
· Lizardi et al.
· 1997
[cited by applicant]
US 5683873A
· George et al.
· 1997
[cited by applicant]
US 5683874A
· Kool
· 1997
[cited by applicant]
US 5728521A
· Yuan et al.
· 1998
[cited by applicant]
US 5861254A
· Schneider et al.
· 1999
[cited by applicant]
US 5861288A
· Usman et al.
· 1999
[cited by applicant]
US 5869248A
· Yuan et al.
· 1999
[cited by applicant]
US 5869253A
· Draper
· 1999
[cited by applicant]
US 5874566A
· Veerapanane et al.
· 1999
[cited by applicant]
US 5877162A
· Werner et al.
· 1999
[cited by applicant]
US 5910408A
· Szostak et al.
· 1999
[cited by applicant]
US 5962426A
· Glazer
· 1999
[cited by applicant]
US 5989906A
· Thompson
· 1999
[cited by applicant]
US 5994320A
· Low et al.
· 1999
[cited by applicant]
US 6017756A
· Draper
· 2000
[cited by applicant]
US 6022962A
· Chowrira et al.
· 2000
[cited by applicant]
US 6030776A
· Eaton et al.
· 2000
[cited by applicant]
US 6046319A
· Power et al.
· 2000
[cited by applicant]
US 6051698A
· Janjic et al.
· 2000
[cited by applicant]
US 6057437A
· Kamiya et al.
· 2000
[cited by applicant]
US 6562347B1
· Kwak et al.
· 2003
[cited by applicant]
US 20010046496A1
· Brettman
· 2001
[cited by examiner]
US 20110082185A1
· Caballero et al.
· 2011
[cited by applicant]
US 20110287036A1
· Matsumura et al.
· 2011
[cited by applicant]
US 20130189367A1
· Zhang et al.
· 2013
[cited by applicant]
US 20130251752A1
· Antonia et al.
· 2013
[cited by applicant]
US 20130261058A1
· Schally et al.
· 2013
[cited by applicant]
US 20140186468A1
· Gonzalo et al.
· 2014
[cited by applicant]
US 20140303133A1
· Pientenpol et al.
· 2014
[cited by applicant]
US 20160272702A1
· Kiaris et al.
· 2016
[cited by applicant]
CN 102319241
· 2012
[cited by applicant]
JP 2010229038
· 2010
[cited by applicant]
JP 2016222656A
· 2016
[cited by examiner]
WO WO8907136
· 1989
[cited by applicant]
WO WO9002806
· 1990
[cited by applicant]
WO WO9718312
· 1997
[cited by applicant]
WO WO9858058
· 1998
[cited by applicant]
WO WO2008052566
· 2008
[cited by applicant]
Honda et al. Pathogenic roles and therapeutic potential of the CCL8-CCR8 axis in a murine model of IgG4-related sialadenitis. Arthritis Res Ther 23, 214 (2021). https://doi.org/10.1186/s13075-021-02597-6 (Year: 2021).
[cited by examiner]
Stone et al. IgG4-Related Disease. N Engl J Med 2012; 366:539-551. DOI: 10.1056/NEJMra1104650. 2012 (Year: 2012).
[cited by examiner]
Medina et al. Ribavirin, human convalescent plasma and anti-B 3 integrin antibody inhibit infection by Sin Nombre virus in the deer mouse model. Journal of General Virology. vol. 88, Issue 2. Published: Feb. 1, 2007 htt…
[cited by examiner]
Griffin et al. SARS-CoV-2 infection and transmission in the North American deer mouse. Nat Commun 12, 3612 (2021). https://doi.org/10.1038/s41467-021-23848-9 (Year: 2021).
[cited by examiner]
Ascoli et al. Overlooked benefits of using polyclonal antibodies. BioTechniques, vol. 65, No. 3. 2018 https://doi.org/10.2144/btn-2018-0065 (Year: 2018).
[cited by examiner]
WIPO translation of the description section of JP-2016222656-A (Year: 2016).
[cited by examiner]
Pathogenic Definition & Meaning—Merriam-Webster: https://www.merriam-webster.com/dictionary/pathogenic. accessed online Dec. 26, 2023 (Year: 2023).
[cited by examiner]
Matute-Bello et al. Animal models of acute lung injury. American Journal of Physiology-Lung Cellular and Molecular Physiology 2008 295:3, L379-L399 (Year: 2008).
[cited by examiner]
Sipahi et al. Experimental Models of Acute Lung Injury. Eurasian J Pulmonol 2014; 16: 69-77, p. 70, 2nd col. 3rd paragraph (Year: 2014).
[cited by examiner]
Miller et al. Inflammation-associated gene transcription and expression in mouse lungs induced by low molecular weight compounds from fungi from the built environment. Chemico-Biological Interactions 183 (2010) 113-124 …
[cited by examiner]
Melchjorsen et al. Expression and function of chemokines during viral infections: from molecular mechanisms to in vivo function. Journal of Leukocyte Biology vol. 74, Sep. 2003 (Year: 2003).
[cited by examiner]
Dulek et al. Allergic Airway Inflammation Decreases Lung Bacterial Burden following Acute Klebsiella pneumoniae Infection in a Neutrophil- and CCL8-Dependent Manner. Infection and Immunity. vol. 82. No. 9. p. 3723-3739 …
[cited by examiner]
Franz Puttur et al. Pulmonary environmental cues drive group 2 innate lymphoid cell dynamics in mice and humans. Sci. Immunol. 4, eaav7638(2019).DOI:10.1126/sciimmunol.aav7638). (Year: 2019).
[cited by examiner]
Kamisawa et al. IgG4-related disease. vol. 385, Iss 9976, P1460-1471. 2015. DOI: https://doi.org/10.1016/S0140-6736(14)60720-0 (Year: 2015).
[cited by examiner]
Khalil et al. (2021). Chemokines and chemokine receptors during COVID-19 infection. Computational and structural biotechnology journal, 19, 976-988 (Year: 2021).
[cited by examiner]
Wigen et al. Converging pathways in pulmonary fibrosis and Covid-19—The fibrotic link to disease severity. Respiratory Medicine: X vol. 2 (2020) 100023 (Year: 2020).
[cited by examiner]
Liu et al. CC Chemokines in Idiopathic Pulmonary Fibrosis: Pathogenic Role and Therapeutic Potential. Biomolecules 2023, 13, 333 . https://doi.org/10.3390/ biom13020333 (Year: 2023).
[cited by examiner]
Naderi et al. Beneficial effects of CCL8 inhibition at lipopolysaccharide-induced lung injury. 2022. vol. 25, Issue 12, 105520 (Year: 2022).
[cited by examiner]
Li et al. 2021. The chemokine CCL1 triggers an AMFR-SPRY1 pathway that promotes differentiation of lung fibroblasts into myofibroblasts and drives pulmonary fibrosis. Immunity 54, 2042-2056 (Year: 2021).
[cited by examiner]
Kawano-Dourado L, Bonfiglioli K, Medeiros-Ribeiro AC, et al. AB0716 Plasma Biomarkers in Rheumatoid Arthritis-Associated Interstitial Lung Disease (RA-ILD): Fibrotic Versus Non-Fibrotic Disease (Bertha Study Baseline Da…
[cited by examiner]
Almagro et al., Humanization of Antibodies, Frontiers in Bioscience, vol. 13, 2008, 1619-1633. https://doi.org/10.2741/2786 https://article.imrpress.com/bri/Landmark/articles/pdf/Landmark2786.pdf.
[cited by applicant]
Ashcroft et al., Simple Method of Estimating Severity of Pulmonary Fibrosis on a Numerical Scale, Journal of Clinical Pathology, vol. 41, No. 4, 1988, 467-470. https://doi.org/10.1136/jcp.41.4.467.
[cited by applicant]
Azadeh et al., The Role of Infection in Interstitial Lung Diseases: A Review, Chest, vol. 152, No. 4, 2017, 842-852. https://doi.org/10.1016/j.chest.2017.03.033.
[cited by applicant]
Baudouin, Manipulation of Inflammation in ARDS: Achievable Goal or Distant Target?, Thorax, vol. 61, No. 6, 2006, 464-465. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2111215/.
[cited by applicant]
Bedford et al., Peromyscus Mice as a Model for Studying Natural Variation, eLIFE Sciences, vol. 4, 2015, e06813, pp. 1-13. https://doi.org/10.7554/elife.06813.
[cited by applicant]
Bennett et al., Evaluation of Cyclosporine-Treated Mice as Hosts for Growing and Testing the Chemosensitivity of First-Transplant-Generation Human Tumor Xenografts Implanted Under the Kidney Capsule, Journal of the Nati…
[cited by applicant]
Bhowmick et al., TGF-β Signaling in Fibroblasts Modulates the Oncogenic Potential of Adjacent Epithelia, Science, vol. 303, Issue No. 5659, 2004, 848-851. https://doi.org/10.1126/science.1090922.
[cited by applicant]
Blanco-Melo et al., Imbalanced Host Response to SARS-CoV-2 Drives Development of COVID-19, Cell, vol. 181, No. 5, 2020, 1036-1045. https://doi.org/10.1016/j.cell.2020.04.026.
[cited by applicant]
Bradley, TNF-Mediated Inflammatory Disease, The Journal of Pathology, vol. 214, Issue 2, 149-160. https://doi.org/10.1002/path.2287.
[cited by applicant]
Cassetta et al., Human Tumor-Associated Macrophage and Monocyte Transcriptional Landscapes Reveal Cancer-Specific Reprogramming, Biomarkers, and Therapeutic Targets, Cancer Cell, vol. 35, No. 4, 2019, 588-602. https://d…
[cited by applicant]
Chatzistamou et al., The Value of Outbred Rodent Models in Cancer Research, Trends in Cancer, vol. 4, No. 7, 2018, 468-471. (Abstract Only) https://doi.org/10.1016/j.trecan.2018.05.004.
[cited by applicant]
Churchill et al., The Collaborative Cross, a Community Resource for the Genetic Analysis of Complex Traits, Nature Genetics, vol. 36, No. 11, 2004, 1133-1137. https://doi.org/10.1038/ng1104-1133.
[cited by applicant]
Day et al., Preclinical Mouse Cancer Models: A Maze of Opportunities and Challenges, Cell, vol. 163, No. 1, 2015, 39-53. https://doi.org/10.1016/j.cell.2015.08.068.
[cited by applicant]
De Genst et al., Antibody Repertoire Development in Camelids, Developmental & Comparative Immunology, vol. 30, vol. 30, 2006, 187-198.
[cited by applicant]
De Souza Xavier Costa et al., Early and Late Pulmonary Effects of Nebulized LPS in Mice: An Acute Lung Injury Model, PLoS One, vol. 12, No. 9, 2017, e0185474, 16 Pages. https://doi.org/10.1371/journal.pone.0185474.
[cited by applicant]
Domscheit et al., Molecular Dynamics of Lipopolysaccharide-Induced Lung Injury in Rodents, Frontiers in Physiology, vol. 11, Article 36, 2020, 8 Pages. https://doi.org/10.3389%2Ffphys.2020.00036.
[cited by applicant]
Fan et al., COVID-19-Associated Acute Respiratory Distress Syndrome: Is a Different Approach to Management Warranted? Lancet, Respiratory Medicine, vol. 8, No. 8, 2020, 816-821. https://doi.org/10.1016/s2213˜2600(20)303…
[cited by applicant]
Farmaki et al., A CCL8 Gradient Drives Breast Cancer Cell Dissemination, Oncogene, vol. 35, No. 49, 2016, 6309-6318. https://doi.org/10.1038/onc.2016.161.
[cited by applicant]
Farmaki et al., CCL8 Promotes Postpartum Breast Cancer by Recruiting M2 Macrophages, iScience, vol. 23, No. 6, 2020, 101217, 18 Pages. https://doi.org/10.1016%2Fj.isci.2020.101217.
[cited by applicant]
Fernandez et al., New Cellular and Molecular Mechanisms of Lung Injury and Fibrosis in Idiopathic Pulmonary Fibrosis, Lancet, vol. 380, No. 9842, 2012, 680-688. https://doi.org/10.1016/s0140-6736(12)61144-1.
[cited by applicant]
Fidler, The Pathogenesis of Cancer Metastasis: The ‘Seed and Soil’ Hypothesis Revisited, Nature Reviews Cancer, vol. 3, 2003, 453-458. https://doi.org/10.1038/nrc1098.
[cited by applicant]
Fingert et al., Transplantation of Human or Rodent Tumors into Cyclosporine-Treated Mice: A Feasible for Studies of Tumor Biology and Chemotherapy, Proceedings of the National Academy of Sciences of the United States of…
[cited by applicant]
Fraser, Long Term Respiratory Complications of COVID-19, BMJ, 2020, 370m3001, 2 Pages. https://doi.org/10.1136/bmj.m3001.
[cited by applicant]
Gallelli et al., Severe Acute Lung Injury Related to COVID-19 Infection: A Review and the Possible Role for Escin, Journal of Clinical Pharmacology, vol. 60, No. 7, 2020, 815-825. https://doi.org/10.1002/jcph.1644.
[cited by applicant]
Gilbert, Advancing Towards Precision Medicine in ARDS, Lancet Respiratory Medicine, vol. 6, Issue 7, 2018, 494-495. https://doi.org/10.1016/S2213-2600(18)30156-5.
[cited by applicant]
Goodman et al., A Model of Human Melanoma in Cyclosporine-Immunosuppressed Rats, Journal of Investigative Dermatology, vol. 88, No. 2, 1987, 141-144. https://doi.org/10.1111/1523˜1747.ep12525289.
[cited by applicant]
Havighorst et al., Differential Regulation of the Unfolded Protein Response in Outbred Deer Mice and Susceptibility to Metabolic Disease, Disease Models & Mechanisms, vol. 12, No. 2, 2019, dmm037242, https://doi.org/10.…
[cited by applicant]
Havighorst et al., Peromyscus as a Model of Human Disease, Seminars in Cell & Developmental Biology, vol. 61, 2017, 150-155. https://doi.org/10.1016/j.semodb.2016.06.020.
[cited by applicant]
Hori et al., CCL8 is a Potential Molecular Candidate for the Diagnosis of Graft-Versus-Host Disease, Blood, vol. 111, No. 8, 2008, 4403-4412. https://doi.org/10.1182/blood-2007-06˜097287.
[cited by applicant]
Igarashi et al., CCL8 Deficiency in Host Strongly Inhibits Early Mortality and Morbidity of Graft-Versus-Host Disease in Mice, Blood, vol. 124, Issue 21, 2014, 1096. https://doi.org/10.1182/blood.V124.21.1096.1096.
[cited by applicant]
Jenkins, IPF: Moving from Idiopathic to Infectious Pulmonary Fibrosis? American Journal of Respiratory and Critical Care Medicine, List of Issues, vol. 196, Issue 2, 2017, 125-127. https://doi.org/10.1164/rccm.201702-03…
[cited by applicant]
King, Idiopathic Pulmonary Fibrosis, Lancet, vol. 378, No. 9807, 2011, 1949-1961. (Abstract Only) https://doi.org/10.1016/s0140-6736(11)60052˜4.
[cited by applicant]
Lebleu, et al. “PGC-1α mediates mitochondrial biogenesis and oxidative phosphorylation in cancer cells to promote metastasis”
[cited by applicant]
Lee et al., Gene Profile of Fibroblasts Identify Relation of CCL8 with Idiopathic Pulmonary Fibrosis, Respiratory Research, vol. 18.3, No. 1, 2017, 12 Pages. https://doi.org/10.1186/s12931˜016˜0493˜6.
[cited by applicant]
Liu et al., Induction of CCL8/MCP-2 by Mycobacteria Through the Activation of TLR2/PI3K/Akt Signaling Pathway, PLoS One, vol. 8, No. 2, 2013, e56815, 12 Pages. https://doi.org/10.1371/journal.pone.0056815.
[cited by applicant]
Luzina et al., Transcriptomic Evidence of Immune Activation in Macroscopically Normal-Appearing and Scarred Lung Tissues in Idiopathic Pulmonary Fibrosis, Cell Immunology, vol. 325, Nos. 1-13, 27 Pages. https://doi.org/…
[cited by applicant]
Mason et al., Acute Respiratory Distress Syndrome, Clinical Medicine, vol. 17, No. 5, 2017, 439-443. https://doi.org/10.7861%2Fclinmedicine.17-5-439.
[cited by applicant]
Ota et al., Upregulation of Plasma CCL8 in Mouse Model of Graft-VS-Host Disease, Experimental Hematology, vol. 37, 2009, 525-531. https://doi.org/10.1016/j.exphem.2008.12.006.
[cited by applicant]
Parameswaran et al., Tumor Necrosis Factor-α Signaling in Macrophages, Crit Rev Eukaryot Gene Expr, vol. 20, No. 2, 2010, 87-103. https://doi.org/10.1615%2Fcritreveukargeneexpr.v20.12.10.
[cited by applicant]
Pitteri et al., Tumor Microenvironment-Derived Proteins Dominate the Plasma Proteome Response During Breast Cancer Induction and Progression, Cancer Research, vol. 71, No. 15, 2011, 5090-5100. https://www.ncbi.nlm.nih.g…
[cited by applicant]
Rafikov et al. Lipopolysaccharide-Induced Lung Injury Involves The Nitration-Mediated Activation of RhoA, Journal of Biological Chemistry, vol. 289, No. 8, 2014, 4710-4722. https://doi.org/10.1074/jbc.m114.547596.
[cited by applicant]
Rajaram et al., System-Wide Analysis Reveals a Complex Network of Tumor-Fibroblast Interactions Involved in Tumorigenicity, PLoS Genetics, vol. 9, Issue 9, e1002789, 2013, 1-16. https://doi.org/10.1371/journal.pgen.1003…
[cited by applicant]
Satija et al., Heterogeneity in Immune Responses: From Populations to Single Cells, Trends in Immunology, vol. 35, No. 5, 2014, 219-229. https://doi.org/10.1016/j.it.2014.03.004.
[cited by applicant]
Schwaiblmair et al., Drug Induced Interstitial Lung Disease, The Open Respiratory Medicine Journal, vol. 6, 2012, 63-74. https://doi.org/10.2174/1874306401206010063.
[cited by applicant]
Severa et al., The Transcriptional Repressor BLIMP1 Curbs Host Defenses by Suppressing Expression of the Chemokine CCL8, Journal of Immunology, vol. 192, No. 5, 2014, 2291-2304. https://doi.org/10.4049/jimmunol.1301799.
[cited by applicant]
Svenson et al., High-Resolution Genetic Mapping Using the Mouse Diversity Outbred Population, Genetics, vol. 190, 2012, 437-447. https://doi.org/10.1534/genetics.111.132597.
[cited by applicant]
Tale et al. Post-COVID-19 Pneumonia Pulmonary Fibrosis, QJM: An International Journal of Medicine, vol. 113, Issue 11, 2020, 837-838. https://doi.org/10.1093/qjmed/hcaa255.
[cited by applicant]
Taub et al., Monocyte Chemotactic Protein-1 (MCP-1), -2, and -3 Are Chemotactic for Human T Lymphocytes, Journal of Clinical Investigation Inc., vol. 95, 1995, 1370-1376. http://dx.doi.org/10.1172/JC1117788.
[cited by applicant]
Thomas et al., CC Chemokines are Differentially Expressed in Breast Cancer and are Associated with Disparity in Overall Survival, Scientific Reports, vol. 9, Article No. 4014, 2019, 12 Pages. https://www.nature.com/arti…
[cited by applicant]
Thoutam et al., Coronavirus: A Shift in Focus Away from IFN Response and Towards Other Inflammatory Targets, Journal of Cell Communication and Signaling, vol. 1-2, 2020, 2 Pages. https://doi.org/10.1007/s12079-020-00574…
[cited by applicant]
Torres et al., Proteome Profiling of Cancer-Associated Fibroblasts Identifies Novel Proinflammatory Signatures and Prognostic Markers for Colorectal Cancer, Clinical Cancer Research, vol. 19, No. 21, 2013, 6006-6019. ht…
[cited by applicant]
Vanharanta et al., Origins of Metastatic Traits, Cancer Cell, vol. 24, Issue 4, 2013, 410-421. https://doi.org/10.1016/j.ccr.2013.09.007.
[cited by applicant]
Wade et al., Genetic Variation in Laboratory Mice, Nature Genetics, vol. 37, No. 11, 2005, 1175-1180. https://doi.org/10.1038/ng1666.
[cited by applicant]
Yoshinaga et al., Ig L-Chain Shuffling for Affinity Maturation of Phage Library-Derived Human Anti-Human MCP-1 Antibody Blocking its Chemotactic Activity, Japanese Biochemical Society, vol. 143, No. 5, 2008, 593-601.
[cited by applicant]