# US 2016/0354431 A1 · Compositions for preserving insulin-producing cells and insulin production and treating diabetes

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- Number: US 2016/0354431 A1
- Document ID: US20160354431A1
- Status: Published application
- Kind: A1
- Application number: 15/181,059
- Filed: 2016-06-13
- Published: 2016-12-08
- Earliest claimed: 2011-10-06
- Assignees: Vanderbilt University
- Applicants: Vanderbilt University
- Inventors: Jack J. Hawiger; Daniel J. Moore; Ruth Ann Veach; Jozef Zienkiewicz
- Web page: https://patentgrep.com/patent/US20160354431A1

## CPC

- A61K 38/17: from animals; from humans {(enzyme inhibitors A61K38/005)}
- C07K 14/4702: {Regulators; Modulating activity}
- C07K 14/62: Insulins
- A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00)
- C07K 2319/10: containing a tag for extracellular membrane crossing, e.g. TAT or VP22
- 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)
- 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)

## Abstract

Nuclear Transport Modifiers such as cSN50 and cSN50.1, afford in vivo islet protection following a 2-day course of intense treatment in autoimmune diabetes-prone, non-obese diabetic (NOD) mice, a widely used model of Type 1 diabetes (T1D), which resulted in a diabetes-free state for one year without apparent toxicity and the need to use insulin. cSN50 precipitously reduces the accumulation of islet-destructive autoreactive lymphocytes while enhancing activation-induced cell death of T and B lymphocytes derived from NOD mice. cSN50 attenuated pro-inflammatory cytokine and chemokine production in immune cells in this model of human T1D. cSN50 also provides cytoprotection of beta cells, therefore preserving residual insulin-producing capacity. Because intracellular delivery of a Nuclear Transport Modifier peptide such as cSN50 and cSN50.1 can result in lowering of fasting blood glucose levels and may ameliorate (e.g., reduce, eliminate) insulin resistance, the compositions, methods and cells described herein can also be used for treating Type 2 diabetes (T2D).

## Claims

### Claim at position 1

1: A composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a Nuclear Transport Modifier comprising the sequence Xaa Xaa Xaa Xaa Leu Leu Pro Xaa Xaa Leu Leu Ala Leu Leu Ala Pro Xaa Xaa Xaa Gln Arg Lys Arg Gln Lys Xaa Xaa Xaa Xaa (SEQ ID NO: 3), wherein Xaa is any amino acid or is absent.

### Claim at position 2 (depends on 1)

2: The composition of claim 1, wherein the Nuclear Transport Modifier is cSN50.1 having the sequence set forth in SEQ ID NO: 2.

### Claim at position 3 (depends on 1)

3: The composition of claim 1, wherein the therapeutically effective amount is sufficient for preserving viability of insulin-producing beta cells and insulin-producing capacity of the cells in a subject.

### Claim at position 4 (depends on 1)

4: The composition of claim 1, wherein the therapeutically effective amount is sufficient for treating Diabetes in a subject.

### Claim at position 5 (depends on 4)

5: The composition of claim 4, wherein the Diabetes is Type 1 or Type 2 Diabetes.

### Claim at position 6

6: Insulin-producing beta cells comprising a Nuclear Transport Modifier comprising the sequence Xaa Xaa Xaa Xaa Leu Leu Pro Xaa Xaa Leu Leu Ala Leu Leu Ala Pro Xaa Xaa Xaa Gln Arg Lys Arg Gln Lys Xaa Xaa Xaa Xaa (SEQ ID NO: 3), wherein Xaa is any amino acid or is absent.

### Claim at position 7 (depends on 6)

7: The insulin-producing beta cells of claim 6, wherein the Nuclear Transport Modifier is cSN50.1 having the sequence set forth in SEQ ID NO: 2.

### Claim at position 8 (depends on 6)

8: The insulin-producing beta cells of claim 6, wherein the Nuclear Transport Modifier is an amount sufficient for decreasing or preventing autoimmune inflammation-induced apoptosis of the population of insulin-producing beta cells.

### Claim at position 9 (depends on 6)

9: The insulin-producing beta cells of claim 6, wherein the Nuclear Transport Modifier is an amount sufficient for decreasing or preventing metabolic inflammation-induced apoptosis of the population of insulin-producing beta cells.

### Claim at position 10 (depends on 6)

10: The insulin-producing beta cells of claim 6, wherein the Nuclear Transport Modifier is in an amount sufficient for preserving viability of the insulin-producing beta cells and insulin-producing capacity of the insulin-producing beta cells.