# US 2010/0166806 A1 · Combination therapy comprising the use of protein kinase C modulators and Histone Deacetylase inhibitors for treating HIV-1 latency

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- Number: US 2010/0166806 A1
- Document ID: US20100166806A1
- Status: Published application
- Kind: A1
- Application number: 12/317,758
- Filed: 2008-12-29
- Published: 2010-07-01
- Earliest claimed: 2008-12-29
- Assignees: Aphios Corporation
- Inventors: Trevor Percival Castor
- Web page: https://patentgrep.com/patent/US20100166806A1

## CPC

- A61K 31/165: having aromatic rings, e.g. colchicine, atenolol, progabide
- A61K 31/19: Carboxylic acids, e.g. valproic acid (salicylic acid A61K31/60)
- A61K 31/366: having six-membered rings, e.g. delta-lactones
- A61P 31/18: for HIV
- C07D 493/22: in which the condensed system contains four or more hetero rings
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

The invention relates to a combination of treatments, more particularly a combination treatment for HIV-1 infection. The present invention is directed to the use of bryostatin-1 and their natural and synthetic derivatives for AIDS therapy, in particular to the use of bryostatins in combination with other active drugs such as Histone Deacetylases (HDACs) inhibitors and anti-retrovirals, for the treatment of HIV-1 latency. According to the present invention, we provide a combination therapy for the treatment of HIV-1 latency which employs bryostatin-1 (and analogues) and one of the following HDAC inhibitors; valproic acid, butyrate derivatives, hydroxamic acids and benzamides. While HDACi can be used in continuous dosing protocol, bryostatins can be used following a cyclical dosing protocol. Bryostatins can be formulated in pharmaceutical acceptable carriers including nanoparticles, phospholipids nanosomes and/or biodegradable polymer nanospheres. This combination therapy needs to be used in patients treated with antiretroviral therapy (HIV-1 protease inhibitors, HIV-1 reverse transcriptase inhibitors, HIV-1 integrase inhibitors, CCR5 co-receptor inhibitors and fusion inhibitors).

## Claims

### Claim 1

A drug for the treatment of HIV/AIDS latency consisting of protein kinase C modulators

### Claim 2 (depends on 1)

In the method of claim 1, the protein kinase C modulator is a cyclic macrolide such as bryostatin 1, bryostatin 2, bryostatin 3 and other bryostatins

### Claim 3 (depends on 2)

In the method of claim 2, bryostatins can be administered at low concentrations that minimize toxic side-effects

### Claim 4 (depends on 3)

In the method of claim 3, bryostatins can be administered at concentrations that would produce a level of around 10 nanomolar in the blood stream.

### Claim 5

A drug for treating HIV/AIDS latency consisting of a combination of: (i) protein kinase C modulators; and (ii) histone deacetylase inhibitors

### Claim 6 (depends on 5)

In the method of claim 5 where the combination of histone deacetylase inhibitors is synergistic with protein kinase C modulators, reducing the required blood concentration of protein kinase C modulator by an order of magnitude to 1 nanomolar

### Claim 7 (depends on 6)

In the method of claim 6, histone deacetylase inhibitors consist of compounds such as valproic acid, phenylbutyrate, hydroxamic acids and benzamides

### Claim 8 (depends on 7)

In the method of claim 7 where the preferred histone deacetylase is valporic acid and TSA

### Claim 9

A drug for treating HIV/AIDS latency consisting of a combination of: (i) protein kinase C modulators; (ii) histone deacetylase inhibitors; and (iii) antivirals.

### Claim 10 (depends on 9)

In the method of claim 9, the antivirals are for the treatment of HIV/AIDS.

### Claim 11 (depends on 10)

In the method of claim 10, the antivirals consist of one or more of the following: (i) protease inhibitors; (ii) nucleoside reverse transcriptase inhibitors; (iii) fusion inhibitors; (iv) integration inhibitors; (v) CCR5 co-receptor inhibitors and/or (vi) maturation inhibitors.

### Claim 12

A drug for treating HIV/AIDS latency consisting of a combination of: (i) protein kinase C modulators; (ii) histone deacetylase inhibitors; (iii) antivirals; and (iv) pharmaceutical acceptable carriers for improving drug stability and delivery.

### Claim 13 (depends on 12)

In the method of claim 12, pharmaceutical acceptable carriers include: (i) nanoparticles of the drugs; (ii) encapsulation of the drugs in phospholipids nanosomes; and/or (iii) biodegradable polymer nanospheres.