METHODS OF ENHANCING IMMUNE RESPONSE

• US 20180161319A1
• Filed: 11/22/2017
• Published: 06/14/2018
• Est. Priority Date: 11/23/2016
• Status: Active Grant

• Current Assignee: Novartis Ag
• Original Assignee: Novartis Ag
• Inventors: Mannick, Joan, Morris, Melody
• Granted Patent: US 10,441,584 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/436 the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
• CPC Class Codes: A61K 31/4745 condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48
• CPC Class Codes: A61P 1/02 Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 13/02 of urine or of the urinary tract, e.g. urine acidifiers
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/16 for influenza or rhinoviruses

Abstract

The present invention relates to a method of enhancing immune response in a subject.

Claims

1. A method comprising the step of administering as a monotherapy a low dose of BEZ235 or a pharmaceutically acceptable salt thereof to a patient, wherein the patient experiences fewer illnesses due to infection than a patient not administered BEZ235 or a pharmaceutically acceptable salt thereof.

2. The method according to claim 1, wherein the patient'"'"'s innate immunity is enhanced.

3. The method according to claim 2, wherein antigen-specific immunity is not enhanced.

4. The method according to claim 2, wherein at least one interferon-inducing gene (ISG) is upregulated.

5. The method according to claim 14, wherein the infection is a urinary tract infection.

6. The method according to claim 14, wherein the infection is a respiratory tract infection.

7. The method according to claim 14, wherein the infection is an oral infection including a periodontal infection.

8. The method according to claim 14, wherein the infection is a viral infection.

9. The method according to claim 1, wherein the patient is elderly.

10. The method according to claim 1, wherein the patient is at least 65 years old.

11. The method according to claim 1, wherein the patient is at least 75 years old.

12. The method according to claim 1, wherein the patient is at least 85 years old.

13. The method according to claim 1, wherein the low dose of BEZ235 or a pharmaceutically acceptable salt thereof, is administered to the patient for up to about 6 consecutive weeks.

14. The method according to claim 13, wherein the patient continues to experience fewer illnesses due to infection from about 1 day until about 1 year after the administration of the BEZ235 or a pharmaceutically acceptable salt thereof.

15. The method according to claim 13, wherein the patient continues to experience fewer illnesses due to infection for at least 1 month and until about 1 year after the administration of the BEZ235 or a pharmaceutically acceptable salt thereof.

16. The method according to claim 13, wherein the patient continues to experience fewer illnesses due to infection for at least 3 months and until about 1 year after the administration of the BEZ235 or a pharmaceutically acceptable salt thereof.

17. The method according to claim 13, wherein the patient continues to experience fewer illnesses due to infection for at least 6 months after the administration of the BEZ235 or a pharmaceutically acceptable salt thereof.

21. The method according to claim 1, wherein the pharmacokinetic AUC variability of patients receiving the low dose of BEZ235 or a pharmaceutically acceptable salt thereof is lower than a patient receiving a higher dose of BEZ235 or a pharmaceutically acceptable salt thereof.

23. The method according to claim 1, wherein BEZ235 or a pharmaceutically acceptable salt thereof is the monotosylate salt.

25. The method according to claim 1, comprising the administration of 1-20 mg of BEZ235 or a pharmaceutically acceptable salt thereof.

26. The method according to claim 1, wherein the subject is immunocompromised.

27. The method according to claim 1, wherein the subject has an impaired immune response.

28. The method according to claim 1, wherein the subject is immunosenescent.

34. The method according to claim 1, wherein the BEZ235 or a pharmaceutically acceptable salt thereof is administered daily to the patient for up to about 16 consecutive weeks.

35. The method according to claim 1, wherein the BEZ235 or a pharmaceutically acceptable salt thereof is administered daily to the patient for up to about 24 consecutive weeks.

18-20. -20. (canceled)

22. (canceled)

24. (canceled)

29. A method of upregulating at least one interferon-inducing gene (ISG), comprising administering as a monotherapy a low dose of BEZ235 or a pharmaceutically acceptable salt thereof, to a patient.

30. A method of upregulating at least one protein involved in extracellular matrix remodeling, comprising administering as a monotherapy a low dose of BEZ235 or a pharmaceutically acceptable salt thereof, to a patient.

31. The method of claim 30, wherein the protein involved in extracellular matrix remodeling is significantly upregulated following treatment for at least about 3 weeks.

32. A method of treating a disease or condition associated with aberrant extracellular matrix remodeling, comprising administering as a monotherapy a low dose of BEZ235 or a pharmaceutically acceptable salt thereof, to a patient.

33. The method of claim 32, wherein the disease or condition associated with aberrant extracellular matrix remodeling is selected from heart failure, heart failure with preserved ejection fraction, chronic renal failure, glomerunephropathy, skin aging, NASH, hepatitis fibrosis/cirrhosis, pulmonary fibrosis including idiopathic pulmonary fibrosis, aging-related tendon dysfunction/stiffening, arthritis including osteoarthritis, sarcopenia, myelofibrosis, myelodysplasia, aging-related dysfunction of the blood brain barrier, diabetic nephropathy, atherosclerosis, or wound healing.