IP Library Granted Patent US 11,298,408
Granted Patent B2
US 11,298,408 · App. 16/331,306 · Granted Apr 12, 2022

Methods of treating hypertension

Inventors: William Hanes (East Setauket, NY); Kevin J. Tracey (Old Greenwich, CT); Peder Olofsson (Lidingö, SE)
Assignee: THE FEINSTEIN INSTITUTES FOR MEDICAL RESEARCH
A61K38/45A61K35/17C12N9/1029C12Y203/01006
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Quick Facts
Patent No.
US 11,298,408
App. No.
16/331,306
Granted
Apr 12, 2022
Kind
B2
Abstract

Provided are CD4+ T-cell-based compositions and methods for treating hypertension.

Claims (20)

1. A method for treating hypertension in a subject, or for reducing development of hypertension in a subject, comprising:

administering to a subject in need thereof an amount of CD4+ T-cells, engineered to express increased levels of choline acetyltransferase relative to non-engineered CD4+ T-cells of the same type, effective to treat or reduce development of hypertension;

wherein the CD4+ T-cells are engineered by having been transformed with a nucleic acid comprising the sequence set forth in SEQ ID NO:1 (hChAT-TAL-VP64);

wherein the CD4+ T-cells have been modified to functionally impair, or to reduce expression of, an endogenous T-cell receptor (TCR) of the T-cell,

wherein the CD4+ T-cells are allogenic to the subject;

wherein the CD4+ T-cells are autologous to the subject;

and/or wherein the CD4+ T-cells are also engineered to further comprise a suicide gene, wherein said suicide gene induces expression of the protein HSV-TK.

2. The method of claim 1 , wherein the method is to treat hypertension in a subject.

3. The method of claim 1 , wherein the method is to reduce development of hypertension in a subject.

4. The method of claim 1 , wherein the CD4+ T-cells are engineered by having been transformed with a nucleic acid comprising the sequence set forth in SEQ ID NO:1 (hChAT-TAL-VP64).

5. The method of claim 1 , wherein the CD4+ T-cells have been modified to functionally impair, or to reduce expression of, an endogenous T-cell receptor (TCR) of the T-cell.

6. The method of claim 1 , wherein the amount of CD4+ T-cells administered is sufficient to effect a reduction in a hypertension symptom in said subject.

7. The method of claim 6 , wherein the reduction in a hypertension symptom is a reduction in mean arterial pressure (MAP) in a subject or a stabilization of MAP of a subject.

8. The method of claim 1 , wherein the CD4+ T-cells are allogenic to the subject.

9. The method of claim 1 , wherein the CD4+ T-cells are autologous to the subject.

10. The method of claim 9 , further comprising obtaining the CD4+ T-cells from the subject prior to engineering the cells to express increased levels of choline acetyltransferase.

11. The method of claim 1 , wherein the CD4+ T-cells are also engineered to further comprise a suicide gene, wherein said suicide gene induces expression of the protein HSV-TK.

12. A method comprising administering to a subject an amount of CD4+ T-cells engineered to express increased levels of choline acetyltransferase relative to non-engineered CD4+ T-cells of the same type, wherein the CD4+ T-cells are engineered by having been transformed with a nucleic acid comprising the sequence set forth in SEQ ID NO:1 (hChAT-TAL-VP64), wherein the CD4+ T-cells have been modified to functionally impair, or to reduce expression of, an endogenous T-cell receptor (TCR) of the T-cell, wherein the CD4+ T-cells are allogenic to the subject, wherein the CD4+ T-cells are autologous to the subject, and/or wherein the CD4+ T-cells are also engineered to further comprise a suicide gene, wherein said suicide gene induces expression of the protein HSV-TK.

13. The method of claim 12 , wherein the CD4+ T-cells are allogenic to the subject.

14. The method of claim 12 , wherein the CD4+ T-cells are autologous to the subject.

Assignments (3)
CONFIRMATORY LICENSE Recorded Nov 7, 2022
From: EINSTEIN INSTITUTE FOR MEDICAL RESEARCH
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 061673/0818 →
CORRECTIVE ASSIGNMENT TO CORRECT THE 2ND PROPERTY NUMBER PREVIOUSLY RECORDED AT REEL: 050188 FRAME: 0819-0826. ASSIGNOR(S) HEREBY CONFIRMS THE ASSIGNMENT. Recorded Nov 10, 2020
From: THE FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH
To: THE FEINSTEIN INSTITUTES FOR MEDICAL RESEARCH
Reel/Frame 054372/0951 →
CHANGE OF NAME Recorded Aug 27, 2019
From: THE FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH
To: THE FEINSTEIN INSTITUTES FOR MEDICAL RESEARCH
Reel/Frame 050188/0819 →
Continuity (2)
Provisional Application 62385335 · Sep 9, 2016
Related Publication 20190201499A1 · Jul 4, 2019