# US 10,117,907 B2 · Glycosylated PACAP/VIP analogues with enhanced CNS penetration for treatment of neurodegenerative diseases

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- Number: US 10,117,907 B2
- Document ID: US10117907B2
- Status: Granted
- Kind: B2
- Application number: 15/044,924
- Filed: 2016-02-16
- Published: 2016-06-16
- Granted: 2018-11-06
- Earliest claimed: 2013-08-14
- Assignees: Arizona Board of Regents on Behalf of the University of Arizona, a body corporate
- Applicants: The Arizona Board of Regents On Behalf of the University of Arizona
- Inventors: Robin Polt; Torsten A E Falk
- Web page: https://patentgrep.com/patent/US10117907B2

## CPC

- A61K 38/1709: {from mammals}
- A61K 38/2278: {Vasoactive intestinal peptide [VIP]; Related peptides (e.g. Exendin)}
- A61P 25/02: for peripheral neuropathies
- C07K 2317/21: from primates, e.g. man
- C07K 2317/41: Glycosylation, sialylation, or fucosylation
- C12N 5/0619: {Neurons}
- G01N 33/6896: {Neurological disorders, e.g. Alzheimer's disease}
- G01N 2800/2814: Dementia; Cognitive disorders
- G01N 2800/2821: Alzheimer
- 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
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

A glycosylated pleiotropic peptide pituitary adenylate cyclase-activating polypeptide (PACAP) which can both agonize PAC1 receptors, causing neuroprotective effects, and antagonize VPAC receptors, causing anti-inflammation in several models of acute neuronal damage and neurodegenerative diseases, including ALS, PD, migraines, and certain forms of dementia, is described. Also described is a method of relieving symptoms of ALS, PD, migraines, and certain forms of dementia, comprising administering to a subject in need thereof an effective amount of a glycosylated PACAP.

## Claims

### Claim 1

A pharmaceutical composition comprising a glycosylated pleiotropic peptide pituitary adenylate cyclase-activating polypeptide (PACAP) in a pharmaceutically acceptable carrier, wherein leucine 1 of said glycosylated PACAP is replaced with serine, and wherein said serine is glycosylated, and wherein said glycosylated PACAP comprises the amino acid sequence of SEQ ID NO:4.

### Claim 2 (depends on 1)

The pharmaceutical composition of claim 1, wherein the glycosylated PACAP comprises the amino acid sequence of SEQ ID NO:4 and is a 27-amino acid peptide.

### Claim 3 (depends on 1)

The pharmaceutical composition of claim 1, wherein the glycosylated PACAP comprises the amino acid sequence of SEQ ID NO:4 and is a 38-amino acid peptide.

### Claim 4 (depends on 1)

The pharmaceutical composition of claim 1, wherein said PACAP is glycosylated with a monosaccharide or disaccharide.

### Claim 5

A glycosylated pleiotropic peptide pituitary adenylate cyclase-activating polypeptide (PACAP), wherein the PACAP comprises the amino acid sequence of SEQ ID NO:3, and wherein leucine 1 of the PACAP is replaced with serine, and wherein said serine is glycosylated.

### Claim 6 (depends on 5)

The glycosylated PACAP of claim 5, wherein the PACAP comprises the amino acid sequence of SEQ ID NO:4 and is a 27-amino acid peptide.

### Claim 7 (depends on 5)

The glycosylated PACAP of claim 5, wherein said PACAP is glycosylated with a monosaccharide or a disaccharide.

### Claim 8 (depends on 5)

The glycosylated PACAP of claim 5, wherein said PACAP is glycosylated with a saccharide selected from the group consisting of ß-D-glucose, ß-maltose, ß-lactose, ß-melibiose, ß-maltotriose, sucrose, trehalose, saccharose, maltose, cellobiose, gentibiose, isomaltose, primeveose, galactose, xylose, mannose, manosaminic acid, fucose, GalNAc, GlcNAc, idose, iduronic acid, glucuronic acid and sialic acid.

### Claim 9 (depends on 1)

A method for promoting neuronal survival and neurite outgrowth in an individual with a neurodegenerative disease comprising administering to the individual in need thereof, a therapeutically effective amount of a composition of claim 1; wherein the neurodegenerative disease is selected from the group consisting of amyotrophic lateral sclerosis (ALS), Parkinson's Disease (PD), traumatic brain injury, stroke and dementia.

### Claim 10 (depends on 2, 9)

The method of claim 9, wherein the method comprises the administration of an effective amount of the glycosylated PACAP-of claim 2.

### Claim 11 (depends on 3, 9)

The method of claim 9, wherein said method comprises the administration of an effective amount of the glycosylated PACAP-of claim 3.

### Claim 12 (depends on 9)

The method of claim 9, wherein the therapeutically effective amount comprises a unit dose amount of between 0.1 and 10 milligrams per kilo.

### Claim 13 (depends on 12)

The method of claim 12, wherein the dose is administered once a day.

### Claim 14 (depends on 12)

The method of claim 12, wherein the dose is administered twice a day.