Low, immune enhancing, dose MTOR inhibitors and uses thereof

Patent metadata

Field	Value
Publication number	US-10286069-B2
Application number	US-201816017173-A
Country	US
Kind code	B2
Filing date	Jun 25, 2018
Priority date	Nov 13, 2013
Publication date	May 14, 2019
Grant date	May 14, 2019

Abstract

The present invention relates, in part, to compositions and methods for enhancement of an immune response by partial mTOR inhibition, e.g., 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 a human subject age 65 or older, comprising administering to the human subject age 65 or older 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 human subject age 65 or older.

2. The method of claim 1 , wherein the human subject age 65 or older is immunocompromised.

3. The method of claim 1 , wherein the human subject age 65 or older has an infectious disease.

4. The method of claim 1 , wherein the human subject age 65 or older has an impaired immune response.

5. The method of claim 1 , wherein the human subject age 65 or older is immunosenescent.

6. The method of claim 1 , comprising treating the human subject age 65 or older for an age related condition.

7. The method of claim 6 , 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, immunosenescence, cancer, obesity, and diabetes.

8. A method of evaluating a human subject age 65 or older 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 human subject age 65 or older, and
comparing the baseline or pre-immunization level of anti-influenza antibody in the elderly human subject to the reference value,
wherein a baseline or pre-immunization level of anti-influenza antibody in the human subject age 65 or older less than the reference value is predictive of a greater RAD001 associated increase in antibody titer for the influenza antigen, and
wherein the human subject age 65 or older, 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.

9. The method of claim 7 , wherein the aging-related mobility disability is frailty.

10. The method of claim 7 , wherein the dementia is age-related dementia.

11. The method of claim 7 , 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

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P9/12

  Antihypertensives · CPC title

• A61P43/00

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

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title