Thiol-mediated drug attachment to targeting peptides

• US 20050118099A1
• Filed: 03/10/2004
• Published: 06/02/2005
• Est. Priority Date: 03/10/2003
• Status: Abandoned Application

• Current Assignee: Biogen Idec MA Inc. (Biogen, Inc.)
• Original Assignee: Biogen Idec MA Inc. (Biogen, Inc.)
• Inventors: Chinn, Paul, Braslawsky, Gary R.
• Application Number:
  US10/796,158
• Publication Number:
  US 20050118099A1
• Time in Patent Office: Days
• US Class Current: 424/1.490
• CPC Class Codes: A61K 47/64 Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent peptidic linkers A61K47/65
• CPC Class Codes: A61K 51/083 the peptide being octreotide or a somatostatin-receptor-binding peptide
• CPC Class Codes: A61K 51/088 conjugates with carriers being peptides, polyamino acids or proteins antibodies A61K51/10
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07K 14/6555 at least 1 amino acid in D-form
• CPC Class Codes: G01N 2333/655 Somatostatins

Abstract

Compositions and methods for thiol-specific attachment of therapeutic and diagnostic agents to somatostatin and other targeting peptides.

Claims

1. A composition comprising a somatostatin analog of the formula:

(A−

B)

wherein;

A is cysteine, or a peptide chain comprising one or more cysteine residues, which is suitable for binding to a drug or chelator via a thiol linkage; and

B is a naturally occurring or synthetic somatostatin peptide, or fragment thereof, that binds to a somatostatin receptor.

2. The composition of claim 1, wherein A comprises the peptide sequence of any one of SEQ ID NOs:

1-3, or wherein A is a single cysteine residue.

3. The composition of claim 1, wherein B comprises SEQ ID NO:

4.

4. The composition of claim 1, wherein the somatostatin analog comprises a peptide of any one of SEQ ID NOs:

5-7.

5. The composition of claim 1, further comprising a drug, or chelator suitable for binding a drug, wherein the drug or chelator is bound to the one or more cysteines by a thiol linkage.

6. The composition of claim 5, wherein the drug is a therapeutic agent or a detectable label.

7. The composition of claim 6, wherein the therapeutic agent is a radioisotope, a cytotoxin, an immunostimulatory agent, an anti-angiogenic agent, a therapeutic gene, or a chemotherapeutic agent.

8. The composition of claim 5, wherein the chelator is a maleimido derivative of DTPA or a maleimido derivative of a DTPA analog.

9. The composition of claim 1, further comprising a somatostatin analog that specifically binds to mammalian SSTR-positive cells in vivo.

10. The composition of claim 1, wherein the SSTR-positive cells are human cancer cells.

11. A method for detecting SSTR-positive cells in a mammalian subject comprising:

(a) administering to the subject a composition comprising a somatostatin analog of the formula;

(A−

B)

wherein;

A is cysteine, or a peptide chain comprising one or more cysteine residues, wherein a detectable label is bound to the one or more cysteine residues via a thiol linkage; and

B is a naturally occurring or synthetic somatostatin peptide, or fragment thereof, which binds to a somatostatin receptor; and

(b) detecting the detectable label, whereby SSTR-positive cells are detected.

12. The method of claim 11, wherein A comprises the peptide sequence of any one of SEQ ID NOs:

1-3, or wherein A is a single cysteine residue.

13. The method of claim 11, wherein B comprises SEQ ID NO:

4.

14. The method of claim 11, wherein the somatostatin analog comprises a peptide of any one of SEQ ID NOs:

5-7.

15. A method for treating an SSTR-associated disorder in a mammalian subject, the method comprising administering to the subject a composition comprising a somatostatin analog of the formula:

(A−

B)

wherein;

A is cysteine, or a peptide chain comprising one or more cysteine residues, wherein a therapeutic agent is bound to the one or more cysteine residues via a thiol linkage; and

B is a naturally occurring or synthetic somatostatin peptide, or fragment thereof, which binds to a somatostatin receptor; and

whereby a SSTR-associated disorder is treated.

16. The method of claim 15, wherein A comprises the peptide sequence of any one of SEQ ID NOs:

1-3, or wherein A is a single cysteine residue.

17. The method of claim 15, wherein B comprises SEQ ID NO:

4.

18. The method of claim 15, wherein the somatostatin analog comprises a peptide of any one of SEQ ID NOs:

5-7.

19. The method of claim 15, wherein the therapeutic agent is selected from the group consisting of a radioisotope, a cytotoxin, an immunostimulatory agent, an anti-angiogenic agent, a therapeutic gene, and a chemotherapeutic agent.

20. The method of claim 15, wherein the SSTR-associated disorder is cancer.