# US 10,369,192 B2 · Methods and compositions for delivery of exogenous factors to nervous system sites

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- Number: US 10,369,192 B2
- Document ID: US10369192B2
- Status: Granted
- Kind: B2
- Application number: 14/078,329
- Filed: 2013-11-12
- Published: 2014-08-14
- Granted: 2019-08-06
- Earliest claimed: 2008-03-05
- Assignees: Regenerative Research Foundation
- Applicants: Regenerative Research Foundation
- Inventors: Sally Temple Stern; Natalia Lowry; Jeffrey Stern; Susan K. Goderie
- Web page: https://patentgrep.com/patent/US10369192B2

## CPC

- A61K 38/1709: {from mammals}
- A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)}
- A61K 9/19: lyophilised {, i.e. freeze-dried, solutions or dispersions (lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00)}
- A61K 35/30: Nerves; Brain; Eyes; Corneal cells; Cerebrospinal fluid; Neuronal stem cells; Neuronal precursor cells; Glial cells; Oligodendrocytes; Schwann cells; Astroglia; Astrocytes; Choroid plexus; Spinal cord tissue
- A61K 38/18: Growth factors; Growth regulators
- A61P 25/00: Drugs for disorders of the nervous system
- C12N 5/0623: {Stem cells}
- 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
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

The present invention relates to treatment methods and methods for sustained delivery of one or more exogenous factors to desired nervous system sites. In certain embodiments, the invention relates to the use of biodegradable microspheres to deliver exogenous factors, such as the morphogenic factor, sonic hedgehog (Shh), to the site of spinal cord injury. In certain embodiments, the Shh-releasing microspheres are administered together with stem cells, which may be spinal cord neural stem cells. In certain embodiments, the invention relates to regrowth of neural cells in both the central and peripheral nervous systems.

## Claims

### Claim 1

A method for treating a spinal cord injury in a mammal in need thereof, comprising administering a pharmaceutical formulation comprising poly lactic-co-glycolic acid (PLGA) microspheres and a single active agent consisting of sonic hedgehog (Shh) at the injury site in an amount effective for treating the spinal cord injury, wherein a single administration provides sustained delivery of the Shh for at least 7 days, and wherein an improvement in motor or sensory function is measured after 28 days from initial administration.

### Claim 2 (depends on 1)

The method of claim 1, wherein the mammal is a human.

### Claim 3 (depends on 1)

The method of claim 1, wherein the pharmaceutical formulation is administered by at least one injection, wherein a first injection is administered at the site of the spinal cord injury.

### Claim 4 (depends on 3)

The method of claim 3, wherein a second injection is administered at a site rostral to the site of the spinal cord injury.

### Claim 5 (depends on 1)

The method of claim 1, wherein said sustained delivery provides at least 5 ng/ml Shh per day for at least 7 days.

### Claim 6

A method for increasing neural cell growth or regenerating neural cells in a mammal having spinal cord injury, comprising administering a sustained release pharmaceutical formulation comprising poly lactic-co-glycolic acid (PLGA) microspheres and a single active agent consisting of sonic hedgehog (Shh) at the injury site in an amount effective for increasing neural cell growth or regenerating neural cells, wherein a single administration provides sustained delivery of the Shh for at least 7 days, and wherein an improvement in motor or sensory function is measured after 28 days from initial administration.

### Claim 7 (depends on 6)

The method of claim 6, wherein the mammal is a human.

### Claim 8 (depends on 6)

The method of claim 6, wherein the neural cell is selected from the group consisting of neurons, glial cells, and progenitor cells.

### Claim 9 (depends on 6)

The method of claim 6, which comprises administering at least one injection of the pharmaceutical formulation at a site at which it is desired to increase neural cell growth or regenerate neural cells.

### Claim 10 (depends on 9)

The method of claim 9, which comprises administering a second injection of the pharmaceutical formulation at a site at which it is desired to increase neural cell growth or regenerate neural cells.