# US 7,611,864 B2 · Proinsulin polypeptide-oligomer conjugates

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- Number: US 7,611,864 B2
- Document ID: US7611864B2
- Status: Granted
- Kind: B2
- Application number: 10/954,787
- Filed: 2004-09-30
- Published: 2005-04-14
- Granted: 2009-11-03
- Earliest claimed: 2004-09-30
- Assignees: Biocon Limited
- Inventors: Balasingam Radhakrishnan; Richard Soltero; Nnochiri N. Ekwuribe
- Web page: https://patentgrep.com/patent/US7611864B2

## CPC

- C07K 14/62: Insulins
- A61K 47/60: the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
- 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

Methods for synthesizing proinsulin polypeptides are described that include a contacting a proinsulin polypeptide including an insulin polypeptide coupled to one or more peptides by peptide bond(s) capable of being cleaved to yield the insulin polypeptide with an oligomer under conditions sufficient to couple the oligomer to the insulin polypeptide portion of the proinsulin polypeptide and provide a proinsulin polypeptide-oligomer conjugate, and cleaving the one or more peptides from the proinsulin polypeptide-oligomer conjugate to provide the insulin polypeptide-oligomer conjugate. Methods of synthesizing proinsulin polypeptide-oligomer conjugates are also described as are proinsulin polypeptide-oligomer conjugates. Methods of synthesizing C-peptide polypeptide-oligomer conjugates are also described.

## Claims

### Claim 1

A proinsulin-oligomer monoconjugate comprising a proinsulin and an oligomer,
wherein the proinsulin comprises an A-chain and a B-chain; a connecting C-peptide coupled at a first end to the C-terminus of the B-chain and coupled at a second end to the N-terminus of the A-chain polypeptide by peptide bonds; and a leader peptide coupled to the N-terminus of the B-chain polypeptide, by a peptide bond, and
wherein the oligomer comprises a hydrophilic moiety and a lipophilic moiety,
wherein the hydrophilic moiety comprises at least one polyalkylene glycol moiety, and
wherein the oligomer is coupled to a lysine residue of the B-Chain of the proinsulin.

### Claim 2 (depends on 1)

The monoconjugate according to claim 1, wherein the insulin polypeptide is human insulin.

### Claim 3 (depends on 1)

The monoconjugate according to claim 1, wherein the insulin polypeptide is insulin and wherein the lysine residue is at the B29 position of the insulin.

### Claim 4 (depends on 1)

The monoconjugate according to claim 1, wherein the polyalkylene glycol moiety is a polyethylene glycol moiety.

### Claim 5 (depends on 4)

The monoconjugate according to claim 4, wherein the polyalkylene glycol moiety has between 4 and 10 polyalkylene glycol subunits.

### Claim 6 (depends on 1)

The monoconjugate according to claim 1, wherein the lipophilic moiety is an alkyl or fatty acid moiety.

### Claim 7 (depends on 1)

The monoconjugate according to claim 1, wherein the lipophilic moiety has between 3 and 8 carbon atoms.

### Claim 8 (depends on 1)

The monoconjugate according to claim 1, wherein the leader peptide is devoid of lysine residues.