IP Library › Granted Patent US 12,409,190
Granted Patent B2
US 12,409,190 · App. 17/595,045 · Granted Sep 9, 2025

Milk derived extracellular vesicles for use in treating inflammatory bowel disease

Inventors: Shimon Reif (Jerusalem, IL); Regina Golan-Gerstl (Maale Michmash, IL)
Assignee: HADASIT MEDICAL RESEARCH SERVICES & DEVELOPMENT LTD.
A61K35/20A61K9/0053A61K9/127A61K31/7105A61K38/1841A61P1/12
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Quick Facts
Patent No.
US 12,409,190
App. No.
17/595,045
Granted
Sep 9, 2025
Kind
B2
Abstract

The present invention is directed to compositions containing exosomes isolated from milk and methods and uses thereof for treating inflammatory bowel disease (IBD) and conditions related thereto. In particular, disclosed are exosomes derived from milk and enteral formulations supplemented therewith for use in treating IBD. The compositions are preferably formulated for rectal administration and the exosomes comprise one or more miRNA molecules and TGF-β.

Claims (18)

1. A method of treating an inflammatory bowel disease (IBD) comprising administering to a subject in need of such treatment a composition comprising a therapeutically effective amount of exosomes isolated from milk by centrifugation and filtration but without any structural modification after isolation, wherein the exosomes comprise one or more miRNA molecules, and TGF-β, wherein the composition is administered by enteral route of administration, thereby treating the IBD.

2. The method according to claim 1 , wherein the milk is bovine, goat, or human milk.

3. The method according to claim 1 , wherein the exosomes are isolated from a skim fraction of the milk and/or from a fat fraction of the milk.

4. The method according to claim 1 , wherein the one or more miRNA molecules are selected from the group consisting of let-7a, miR-320, miR-375, and miR-148a.

5. The method according to claim 1 , wherein the TGF-β is TGF-β1.

6. The method according to claim 1 , wherein the exosomes further comprise at least one biologically active compound selected from the group consisting of proteins, peptides, nucleic acid molecules, and lipids.

7. The method according to claim 1 , wherein the exosomes comprise less than about 20% (w/w) casein of the total protein of the exosomes.

8. A method of treating an inflammatory bowel disease (IBD) selected from the group consisting of Crohn's disease and ulcerative colitis, comprising administering to a subject in need of such treatment a composition comprising a therapeutically effective amount of exosomes isolated from milk by centrifugation and filtration but without any structural modification after isolation, wherein the exosomes comprise one or more miRNA molecules, and TGF-β, wherein the composition is administered by enteral route of administration, thereby treating the IBD.

9. The method according to claim 8 , wherein ulcerative colitis is distal colitis.

10. The method according to claim 9 , wherein distal colitis is selected from the group consisting of proctitis, proctosigmoiditis, and left-sided colitis.

11. The method according to claim 1 , wherein the composition is administered by oral administration or by tube feeding.

12. The method according to claim 1 wherein the composition is administered by rectal administration.

13. The method according to claim 12 , wherein the composition is formulated as an enema, suppository, or foam.

14. The method according to claim 1 , wherein the therapeutically effective amount of the exosomes ranges from about 0.1 mg to about 250 mg/kg body weight of the subject.

15. The method according to claim 13 , wherein the milk in the composition is bovine, goat, or human natural milk.

16. The method according to claim 15 , wherein the one or more miRNA molecules are selected from the group consisting of let-7a, miR-320, miR-375, and miR-148a.

17. The method according to claim 15 , wherein the exosomes further comprise at least one biologically active compound selected from the group consisting of proteins, peptides, nucleic acid molecules, and lipids.

18. A method of treating an inflammatory bowel disease (IBD) comprising administering to a subject in need of such treatment a composition comprising a therapeutically effective amount of exosomes isolated from bovine, goat, or human milk by centrifugation and filtration but without any structural modification after isolation, wherein the exosomes comprise one or more miRNA molecules selected from the group consisting of let-7a, miR-320, miR-375, and miR-148a and comprise less than about 20% (w/w) casein of the total protein of the exosomes, with the composition further comprising TGF-β1 and at least one biologically active compound selected from the group consisting of proteins, peptides, nucleic acid molecules, and lipids, wherein the composition is administered by enteral route of administration and the therapeutically effective amount of the exosomes ranges from about 0.1 mg to about 250 mg/kg body weight of the subject, thereby treating the IBD.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 7, 2021
From: REIF, SHIMON; GOLAN-GERSTL, REGINA
To: HADASIT MEDICAL RESEARCH SERVICES & DEVELOPMENT LTD.
Reel/Frame 058039/0218 →
Continuity (2)
Provisional Application 62847339 · May 14, 2019
Related Publication 20220202866A1 · Jun 30, 2022
References Cited (51)
US 10874114B2 · Reif · 2020 [cited by examiner]
US 20040097714A1 · Maubois et al. · 2004 [cited by applicant]
US 20140302205A1 · Melnik · 2014 [cited by applicant]
US 20160000710A1 · Gupta et al. · 2016 [cited by applicant]
US 20180343882A1 · Reif et al. · 2018 [cited by applicant]
CN 101874108A · 2010 [cited by applicant]
CN 105412153A · 2016 [cited by applicant]
EP 1800675A1 · 2007 [cited by applicant]
EP 2455486A1 · 2012 [cited by applicant]
EP 2896294A1 · 2015 [cited by applicant]
EP 3192518A1 · 2017 [cited by examiner]
FR 2827290A1 · 2003 [cited by applicant]
WO WO2013023982A1 · 2012 [cited by applicant]
WO WO2014036726A1 · 2014 [cited by applicant]
WO WO2014134132A1 · 2014 [cited by applicant]
WO WO2017090049A1 · 2017 [cited by examiner]
WO 2018102397A1 · 2018 [cited by applicant]
WO WO2018170332A1 · 2018 [cited by examiner]
WO WO2019236873A1 · 2019 [cited by examiner]
Axelrad et al. (2016) World J. Gastroenterol. 22(20): 4794-4801. (Year: 2016). [cited by examiner]
Casella et al. (2010) J. Crohn's and Colitis 4, 384-389. (Year: 2010). [cited by examiner]
Danese et al. (2005) World J. Gastroenterol. 11(46): 7227-7236. (Year: 2005). [cited by examiner]
Pieters et al. (2015) PLoS ONE 10(3): 14 pages (Year: 2015). [cited by examiner]
Veloso (2004) Aliment. Pharmacol. Ther. 20(Suppl. 4): 50-53. (Year: 2004). [cited by examiner]
Chen et al., “Decreased miRNA-148a is associated with lymph node metastasis and poor clinical outcomes and functions as a suppressor of tumor metastasis in non-small cell lung cancer,” Oncology Reports, 30: 1832-1840 (2… [cited by applicant]
Melnik et al., “Milk: an exosomal microRNA transmitter promoting thymic regulatory T cell maturation preventing the development of atopy?,” Journal of Translational Medicine, 12:43 (2014). [cited by applicant]
Admyre et al., (2007) Exosomes with immune modulatory features are present in human breast milk. J Immunol 179 (3): 1969-1978. [cited by applicant]
Alsaweed et al., (2015) MicroRNAs in Breastmilk and the Lactating Breast: Potential Immunoprotectors and Developmental Regulators for the Infant and the Mother. Int J Environ Res Public Health 12(11): 13981-14020. [cited by applicant]
Arntz et al., (2015) Oral administration of bovine milk derived extracellular vesicles attenuates arthritis in two mouse models. Mol Nutr Food Res 59(9): 1701-1712. [cited by applicant]
Benmoussa et al., “Concentrates of two subsets of extracellular vesicles from cow's milk modulate symptoms and inflammation in experimental colitis,” Scientific Reports, 9:14661 (2019). [cited by applicant]
Bernstein et al., (2001) Cancer risk in patients with inflammatory bowel disease: a population-based study. Cancer 91(4): 854-862. [cited by applicant]
Chen et al., (2016) Porcine milk-derived exosomes promote proliferation of intestinal epithelial cells. Sci Rep 6: 33862; 12 pages. [cited by applicant]
El Andaloussi et al., (2013) Extracellular vesicles: biology and emerging therapeutic opportunities. Nat Rev Drug Discov 12(5): 347-357. [cited by applicant]
Golan-Gerstl et al., (2016) Expression and biological function of miRNA in breast milk. 10th Congress of the International Society of Nutrigenetics/Nutrigenomics (ISNN). May 22-26, 2016, Tel Aviv, Israel. J Nutrigenet N… [cited by applicant]
Golan-Gerstl et al., (2017) Characterization and biological function of milk-derived miRNAs. Mol Nutr Food Res 61(10): 1700009; 11 pages. [cited by applicant]
Hartnett and Egan (2012) Inflammation, DNA methylation and colitis-associated cancer. Carcinogenesis 33(4): 723-731. [cited by applicant]
Kanwar et al., (2016) Comparative activities of milk components in reversing chronic colitis. J Dairy Sci 99(4): 2488-2501. [cited by applicant]
Mao et al., (2017) Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells Relieve Inflammatory Bowel Disease in Mice. Biomed Res Int 2017: 5356760; 13 pages. [cited by applicant]
Pieters et al., (2015) Commercial cow milk contains physically stable extracellular vesicles expressing immunoregulatory TGF-β. PLoS One 10(3): e0121123; 14 pages. [cited by applicant]
Verhasselt et al., (2008) Breast milk-mediated transfer of an antigen induces tolerance and protection from allergic asthma. Nat Med 14(2): 170-175. [cited by applicant]
Wang et al., (2017) Exosomes Derived from Dendritic Cells Treated with Schistosoma japonicum Soluble Egg Antigen Attenuate DSS-Induced Colitis. Front Pharmacol 8: 651; 10 pages. [cited by applicant]
Wolf et al., (2015) The Intestinal Transport of Bovine Milk Exosomes Is Mediated by Endocytosis in Human Colon Carcinoma Caco-2 Cells and Rat Small Intestinal IEC-6 Cells. J Nutr 145(10): 2201-2206. [cited by applicant]
Yang et al., (2015) Extracellular Vesicles Derived from Bone Marrow Mesenchymal Stem Cells Protect against Experimental Colitis via Attenuating Colon Inflammation, Oxidative Stress and Apoptosis. PLoS One 10(10): e01405… [cited by applicant]
Zhou et al., (2012) Immune-related microRNAs are abundant in breast milk exosomes. Int J Biol Sci 8(1): 118-123. [cited by applicant]
International Application No. PCT/IL2020/050518, International Search Report, mailed Aug. 18, 2020. [cited by applicant]
International Application No. PCT/IL2020/050518, Written Opinion of the International Searching Authority, mailed Aug. 18, 2020. [cited by applicant]
Li et al., “Bovine milk-derived exosomes enhance goblet cell activity and prevent the development of experimental necrotizing enterocolitis,” PLoS ONE 14(1): e0211431 (2019). [cited by applicant]
Ordas et al., “Anti-TNF Monoclonal Antibodies in Inflammatory Bowel Disease: Pharmacokinetics-Based Dosing Paradigms,” Clinical Pharmacology & Therapeutics, 91(4): 635-646 (2012). [cited by applicant]
Huguet et al., “Systematic Review With Meta-Analysis: Anti-TNF Therapy in Refractory Pouchitis and Crohn's Disease—Like Complications of the Pouch After lleal Pouch-Anal Anastomosis Following Colectomy for Ulcerative Co… [cited by applicant]
Akane Hasegawa, 2011, vol. 49, No. 6, pp. 392-397. [cited by applicant]
Hibi et al, 2001, vol. 22, No. 2, pp. 115-121. [cited by applicant]