# US 10,308,701 B2 · Modified glucagon molecules

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- Number: US 10,308,701 B2
- Document ID: US10308701B2
- Status: Granted
- Kind: B2
- Application number: 15/745,483
- Filed: 2016-07-22
- Published: 2018-10-18
- Granted: 2019-06-04
- Earliest claimed: 2015-07-22
- Assignees: Purdue Research Foundation
- Applicants: Purdue Research Foundation
- Inventors: Elizabeth M. Murphy Topp; Hamed Tabatabaei Ghomi; Markus Lill; Shenbaga Moorthy Balakrishnan
- Web page: https://patentgrep.com/patent/US10308701B2

## CPC

- C07K 14/605: Glucagons
- A61K 38/26: Glucagons
- A61K 47/52: the modifying agent being an inorganic compound, e.g. an inorganic ion that is complexed with the active ingredient
- 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: 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)
- 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)

## Abstract

The invention generally relates to modified glucagon molecules. In certain embodiments, the invention provides a glucagon molecule that includes one or more modified amino acids, e.g., phosphorylation and/or sulfation, to result in the glucagon molecule being soluble at a substantially neutral pH and resistant to fibrillation.

## Claims

### Claim 1

A glucagon molecule comprising one or more phosphorylated amino acids.

### Claim 2 (depends on 1)

The glucagon molecule according to claim 1, wherein the glucagon molecule comprises two or more phosphorylated amino acids.

### Claim 3 (depends on 1)

The glucagon molecule according to claim 1, wherein the glucagon molecule comprises three or more phosphorylated amino acids.

### Claim 4 (depends on 1)

The glucagon molecule according to claim 1, wherein the one or more phosphorylated amino acids are selected from the group consisting of His1, Ser2, Thr5, Thr7, Ser8, Tyr10, Ser11, Tyr13, Ser16, Thr29, and combinations thereof.

### Claim 5 (depends on 4)

The glucagon molecule according to claim 4, wherein the one or more phosphorylated amino acids are selected from the group consisting of Thr5, Ser8, Ser16 and combinations thereof.

### Claim 6

A glucagon prodrug comprising one or more modified amino acids such that the glucagon prodrug is soluble at a substantially neutral pH, wherein the one or more modified amino acids are modified with a functional group that imparts a charge to the one or more modified amino acids and the functional group is cleaved upon administration of the prodrug, and wherein the one or more modified amino acids are one or more amino acids that have been modified with a phosphate group and the one or more amino acids that have been modified with a phosphate group are selected from the group consisting of Thr5, Ser8, and combinations thereof.

### Claim 7 (depends on 6)

The glucagon prodrug according to claim 6, wherein the functional group is chemically or enzymatically cleaved.

### Claim 8 (depends on 6)

The glucagon prodrug according to claim 6, wherein two amino acids have been modified with a phosphate group.
