Peptide analogues of insulin-like growth factor 1 (IGF-1) or factor 2 (IGF-2)

• US 5,164,370 A
• Filed: 08/24/1989
• Issued: 11/17/1992
• Est. Priority Date: 12/24/1987
• Status: Expired due to Term

• Current Assignee: Novozymes Biopharma DK A/S (Novozymes)
• Original Assignee: Gropep, Ltd.
• Inventors: Ballard, Francis J., Wells, Julian R. E., Wallace, John C.
• Primary Examiner(s): Cashion, Jr., Merrell C.
• Assistant Examiner(s): NOT, DEFINED
• Application Number:
  US07/408,518
• Time in Patent Office: 1,181 Days
• Field of Search: 514/2, 514/12, 514/3, 514/4, 530/330, 530/331, 530/303, 530/324, 930/120
• US Class Current: 514/8.5
• CPC Class Codes: 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
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 14/65 Insulin-like growth factors, i.e. somatomedins, e.g. IGF-1, IGF-2
• CPC Class Codes: Y10S 930/12 Growth hormone, growth factor other than t-cell or b-cell growth factor, and growth hormone releasing factor; related peptides

Abstract

Peptide analogues of insulin-like growth factor 1 and growth factor 2 are disclosed. When the analogue is an analogue of growth factor 1 the glutamic acid residue is absent from position 3 of the N-terminal and either the glutamic acid residue or the threonine residue adjacent to glutamic acid residue at position 3 is replaced by a different amino acid residue. When the peptide analogue is an analogue of insulin growth factor 2 the glutamic acid residue position 5 is absent. Preferred peptide analogues are disclosed. Methods of use in pharmaceutical and veterinary preparations are described.

Claims

1. A peptide analogue of insulin growth factor-1 (IGF-1) having a modified N-terminal sequence selected from:

##STR1## with the Cys residue shown being that normally at position 6 from the N-terminal, the remainder of the sequence corresponding to a human, bovine, ovine, porcine or chicken insulin growth factor-1.

2. A peptide analogue according to claim 1 which is human, bovine or porcine insulin growth factor-1 analogue.

3. A peptide analogue according to claim 2 in a biologically pure form.

4. A peptide analogue of insulin growth factor-2 (IGF-2) having a modified N-terminal sequence selected from:

Ala-Thr-Arg-Pro-Ser-Lys-Thr-Leu-Cys-Ala-Tyr-Arg-Pro-Ser-Arg-Thr-Leu-Cys-Ala-Tyr-Arg-Pro-Ser-Gly-Arg-Leu-Cys-Ala-Tyr-Arg-Pro-Ser-Gly-Arg-Leu-Cys-

with the Cys residue shown being that normally at position 9 from the N-terminal, the remainder of the sequence corresponding to a human, bovine, ovine, porcine or chicken insulin growth factor-2.

5. A peptide analogue according to claim 4 which is human, bovine, or porcine insulin growth factor-2 analogue.

6. A peptide analogue according to claim 5 in a biologically pure form.

7. A pharmaceutical or veterinary composition for the treatment of protein loss in humans or animals respectively, including an effective amount of a peptide analogue of insulin growth factor-1 (IGF-1) having a modified N-terminal sequence selected from:

##STR2## with the Cys residue shown being that normally at position 6 from the N-terminal, the remainder of the sequence corresponding to a human, bovine, ovine, porcine or chicken insulin growth factor-1.

8. A pharmaceutical or veterinary composition for the treatment of protein loss in humans or animals respectively, including an effective amount of a peptide analogue of insulin growth factor-2 (IGF-2) having a modified N-terminal sequence selected from:

Ala-Thr-Arg-Pro-Ser-Lys-Thr-Leu-Cys-Ala-Tyr-Arg-Pro-Ser-Arg-Thr-Leu-Cys-Ala-Tyr-Arg-Pro-Ser-Gly-Arg-Leu-Cys-Ala-Tyr-Arg-Pro-Ser-Gly-Thr-Leu-Cys-

with the Cys residue shown being that normally at position 9 from the N-terminal, the remainder of the sequence corresponding to a human, bovine, ovine, porcine or chicken insulin growth factor-2.