Low, immune enhancing, dose mtor inhibitors and uses thereof

Patent metadata

Field	Value
Publication number	US-10004803-B2
Application number	US-201615292088-A
Country	US
Kind code	B2
Filing date	Oct 12, 2016
Priority date	Nov 13, 2013
Publication date	Jun 26, 2018
Grant date	Jun 26, 2018

Abstract

The present invention relates, in part, to compositions and methods for enhancement of an immune response by partial mTOR inhibition, for example, with low, immune enhancing, doses of an mTOR inhibitor, such as RAD001.

First claim

What is claimed is:

1. A method of promoting an immune response in an immunosenescent human subject, comprising administering to the immunosenescent human subject a low, immune enhancing, dose of about 0.1 mg of RAD001, orally and once daily, thereby enhancing or promoting an immune response in the immunosenescent human subject.

2. The method of claim 1 , wherein the immunosenescent human subject is immunocompromised.

3. The method of claim 1 , wherein the immunosenescent human subject has an infectious disease.

4. The method of claim 1 , wherein the immunosenescent human subject has an impaired immune response.

5. The method of claim 1 , comprising treating the immunosenescent human subject for an age related condition.

6. The method of claim 5 , wherein the age related condition is selected from the group consisting of sarcopenia, skin atrophy, muscle wasting, brain atrophy, atherosclerosis, arteriosclerosis, pulmonary emphysema, osteoporosis, osteoarthritis, high blood pressure, erectile dysfunction, dementia, Huntington's disease, Alzheimer's disease, cataracts, age-related macular degeneration, prostate cancer, stroke, diminished life expectancy, impaired kidney function, and age-related hearing loss, aging-related mobility disability, cognitive decline, memory impairment, tendon stiffness, heart dysfunction, cancer, obesity, and diabetes.

7. A method of evaluating an immunosenescent human subject for treatment with a low, immune enhancing, dose of RAD001 to promote or enhance an immune response to an influenza vaccine or antigen, comprising:
establishing a reference baseline or pre-immunization level of anti-influenza antibody,
measuring a baseline or pre-immunization level of anti-influenza antibody in the immunosenescent human subject, and
comparing the baseline or pre-immunization level of anti-influenza antibody in the immunosenescent human subject to the reference value,
wherein a baseline or pre-immunization level of anti-influenza antibody in the immunosenescent human subject less than the reference value is predictive of a greater RAD001 associated increase in antibody titer for the influenza antigen,
and wherein the immunosenescent human subject, once evaluated, is then treated with a low, immune enhancing dose of RAD001,
wherein treatment comprises administering a dose of about 0.1 mg of RAD001, orally and once daily.

8. A composition comprising
(a) a vaccine antigen; and
(b) about 0.1 mg of RAD001.

9. The method of claim 6 , wherein the aging-related mobility disability is frailty.

10. The method of claim 6 , wherein the dementia is age-related dementia.

11. The method of claim 6 , wherein the heart dysfunction is cardiac hypertrophy or systolic or diastolic dysfunction.

Assignees

• Novartis Ag

Inventors

• Mannick Joan
• Glass David
• Murphy Leon

Classifications

• A61K31/436 Primary

  the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin · CPC title

• A61P37/04

  Immunostimulants · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P9/12

  Antihypertensives · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title