Calcitonin drug-oligomer conjugates, and uses thereof

• US 7,713,932 B2
• Filed: 11/08/2002
• Issued: 05/11/2010
• Est. Priority Date: 06/04/2001
• Status: Expired due to Fees

• Current Assignee: Biocon Limited (Biocon Incorporated)
• Original Assignee: Biocon Limited (Biocon Incorporated)
• Inventors: Radhakrishnan, Balasingam, Ekwuribe, Nnochiri N.
• Primary Examiner(s): Tate; Christopher R.
• Assistant Examiner(s): TELLER, ROY R
• Application Number:
  US10/166,355
• Publication Number:
  US 20040091452A1
• Time in Patent Office: 2,741 Days
• Field of Search: None
• US Class Current: 514/11.9
• CPC Class Codes: A61K 47/60 the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: C07K 14/585 Calcitonins

Abstract

Calcitonin drug-oligomer conjugates that include a calcitonin drug coupled to an oligomer including a single polyalkylene glycol moiety consisting of between 4 and 10 polyalkylene glycol subunits are disclosed. Pharmaceutical compositions including such conjugates and methods of treating bone disorders by administering such conjugates are also disclosed.

Claims

1. A substantially monodispersed calcitonin oligomer conjugate mixture consisting of a salmon calcitonin coupled to two oligomer subunits, wherein each oligomer comprises a polyalkylene glycol moiety, wherein the conjugate consists of a first oligomer subunit and a second oligomer subunit wherein the first oligomer subunit is covalently coupled to Lys¹¹ of the calcitonin drug and the second oligomer subunit is covalently coupled to Lys¹⁸ of the calcitonin drug, wherein the substantially monodispersed calcitonin drug-oligomer conjugate consisting of the structure of Formula I:

2. The conjugate according to claim 1, wherein the calcitonin drug is salmon calcitonin.

3. The conjugate according to claim 1, wherein the oligomer is covalently coupled to an amine function of the calcitonin drug.

4. The conjugate according to claim 1, wherein the oligomer consist of a first oligomer and a second oligomer subunit, and wherein the first oligomer subunit and second oligomer subunit can be the same or different.

5. The conjugate according to claim 1, wherein x is from 7 to 9.

6. The conjugate according to claim 1, wherein y is from 4 to 8.

7. The conjugate according to claim 1, wherein x is 7 and y is 7.

8. A pharmaceutical composition comprising the conjugate mixture of claim 1;

and

a pharmaceutically acceptable carrier.

9. The pharmaceutical composition according to claim 8, wherein the oligomer is covalently coupled to an amine function of the calcitonin drug.

10. The pharmaceutical composition according to claim 8, wherein x is 9, y is 7, and z is 2.

11. The pharmaceutical composition according to claim 8, wherein x is 6, y is 8, and z is 2.

12. A method of treating a bone disorder in a subject in need of such treatment, said method comprising:

administering an effective amount of the calcitonin drug-oligomer conjugate according to claim 1 to the subject to treat the bone disorder.

13. The method according to claim 12, wherein the administration is oral.