IP Library › Granted Patent US 12,343,376
Granted Patent B2
US 12,343,376 · App. 18/444,102 · Granted Jul 1, 2025

Methods for inhibiting diazepam binding protein

Inventors: Guido Kroemer (Paris, FR); José Manuel Bravo San Pedro (Paris, FR)
Assignees: INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE; ASSISTANCE PUBLIQUE-HÔPITAUX DE PARIS (APHP); UNIVERSITÉ PARIS CITÉ; SORBONNE UNIVERSITÉ
A61K38/17A61K39/0005A61K39/39A61P3/04C07K16/18C07K16/286G01N33/68A61K2039/505A61K2039/545C07K2317/21C07K2317/24
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Quick Facts
Patent No.
US 12,343,376
App. No.
18/444,102
Granted
Jul 1, 2025
Kind
B2
Abstract

Autophagy is typically activated by starvation, allowing cells and organisms to mobilize their energy reserves. It is known that pharmacological modulation of autophagy represents a therapeutic potential. Here the inventors report that a protein that is released from cells in an unconventional, autophagy-dependent manner, namely, diazepam binding inhibitor (DBI), regulates autophagy. In particular, the inventors demonstrate that DBI inhibits autophagy and that the supply of recombinant DBI to mice enhanced glycolysis, enhanced lipogenesis, and inhibited fatty acid oxidation. The inventors show that neutralisation of DBI by a monoclonal antibody and an active immunization by means of an immunogenic DBI derivative eliciting autoantibodies induce autophagy and lead to metabolic changes that increase starvation-induced weight loss, reduce food intake upon refeeding, and reduce weight gain in response to hypercaloric diets. Accordingly, the present invention relates to methods and pharmaceutical compositions for modulating autophagy based on the modulation of the activity or expression of DBI.

Claims (17)

1. A method comprising contacting a tissue of a patient with an antibody that binds human extracellular diazepam binding inhibitor (DBI) at a dosage sufficient to reduce the activity of human extracellular DBI in the patient, as determined in an in vitro assay performed on a sample obtained from the patient, wherein the patient suffers from metabolic syndrome.

2. The method of claim 1 , wherein the tissue is a liver tissue.

3. The method of claim 2 , wherein the dosage is sufficient to reduce an hepatic lipogenesis-stimulatory factor (FASN) in the liver tissue of the patient, relative to a level of FASN in the liver tissue prior to the contacting.

4. The method of claim 1 , wherein the tissue is a brown adipose tissue.

5. The method of claim 4 , wherein the dosage is sufficient to increase an uncoupling protein 1 (UCP1) in the brown adipose tissue of the patient, relative to a level of UCP1 prior to the contacting.

6. The method of claim 1 , wherein the dosage is sufficient to increase plasma glucose levels in the patient, as determined in an in vitro assay, relative to prior to contacting.

7. The method of claim 1 , wherein the dosage is sufficient to reduce plasma insulin levels in the patient, relative to prior to the contacting.

8. The method of claim 1 , wherein the dosage is sufficient to reduce C-peptide levels in the patient, relative to prior to the contacting.

9. The method of claim 1 , wherein the dosage is sufficient to reduce a gastric inhibitory peptide in the patient, relative to prior to the contacting.

10. The method of claim 1 , wherein the antibody is a monoclonal antibody.

11. The method of claim 10 , wherein the monoclonal antibody is a chimeric antibody, a monoclonal humanised antibody, or a monoclonal human antibody.

12. The method of claim 1 , wherein the patient suffering from the metabolic syndrome is overweight.

13. The method of claim 1 , wherein the patient suffering from the metabolic syndrome also suffers from liver disease.

14. The method of claim 13 , wherein the liver disease is a non-alcoholic fatty liver disease (NAFLD).

15. The method of claim 14 , wherein the NAFLD is nonalcoholic steatohepatitis (NASH).

16. The method of claim 1 , wherein the patient suffering from the metabolic syndrome also suffers from diabetes.

17. The method of claim 1 , wherein the patient suffering from the metabolic syndrome also suffers from cancer.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 21, 2024
From: KROEMER, GUIDO; BRAVO SAN PEDRO, JOSE MANUEL
To: INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE; ASSISTANCE PUBLIQUE-HÔPITAUX DE PARIS (APHP); SORBONNE UNIVERSITÉ; UNIVERSITE DE PARIS
Reel/Frame 066641/0775 →
CHANGE OF NAME Recorded Feb 21, 2024
From: UNIVERSITE DE PARIS
To: UNIVERSITÉ PARIS CITÉ
Reel/Frame 066642/0027 →
Priority Claims (1)
EP 173062293 · Sep 20, 2017 · regional
Continuity (3)
Continuation 17935261 · Sep 26, 2022
Continuation 16648744
Related Publication 20240245750A1 · Jul 25, 2024
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