Biotinylated compositions

• US 8,669,236 B2
• Filed: 05/12/2006
• Issued: 03/11/2014
• Est. Priority Date: 05/12/2005
• Status: Active Grant

• Current Assignee: Children's Medical Center Corporation, The General Hospital Corporation (Mass General Brigham, Inc.)
• Original Assignee: Children's Medical Center Corporation, The General Hospital Corporation (Mass General Brigham, Inc.)
• Inventors: Elmaleh, David R., Zetter, Bruce R., Weinstein, Earl, Bhisitkul, Jacqueline Banyard
• Primary Examiner(s): WHITEMAN, BRIAN A
• Application Number:
  US11/914,332
• Publication Number:
  US 20090220433A1
• Time in Patent Office: 2,860 Days
• Field of Search: 435/6, 435/91.1, 435/91.31, 435/455, 514/1, 514/2, 514/44, 514/44.A, 536/23.1, 536/24.5, 536/26.6, 536/106, 536/127
• US Class Current: 514/44.A
• CPC Class Codes: A61K 47/549 Sugars, nucleosides, nucleotides or nucleic acids
• CPC Class Codes: A61K 47/551 one of the codrug's components being a vitamin, e.g. niacinamide, vitamin B3, cobalamin, vitamin B12, folate, vitamin A or retinoic acid
• CPC Class Codes: A61K 47/557 the modifying agent being biotin
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C12N 15/111 General methods applicable to biologically active non-coding nucleic acids
• CPC Class Codes: C12N 15/1135 against oncogenes or tumor suppressor genes
• CPC Class Codes: C12N 2310/14 interfering N.A.
• CPC Class Codes: C12N 2310/351 Conjugate
• CPC Class Codes: C12N 2320/32 Special delivery means, e.g. tissue-specific

Abstract

Novel biotinylated composition comprising a nucleic acid, e.g. siRNA, that are useful for targeting therapeutic and imaging agents to sites of infection and tumors are disclosed.

Claims

1. A composition consisting of a polymer scaffold conjugated to (i) one, two, three, or four biotin moieties, and (ii) one or two therapeutic double-stranded RNA molecules having a sense strand and an antisense strand, wherein the sense or the antisense strand is conjugated to one or two biotin moieties.

2. The composition of claim 1, wherein said therapeutic double-stranded RNA molecule is siRNA.

3. The composition of claim 1, wherein the sense strand is conjugated to two biotin moieties.

4. The composition of claim 1, wherein the antisense strand is conjugated to two biotin moieties.

5. The composition of claim 1, wherein the sense strand and the antisense strand are each conjugated to two biotin moieties.

6. A pharmaceutical composition, comprising a composition of claim 1 or claim 2, and a pharmaceutically acceptable excipient.

7. The composition of claim 1, wherein the sense strand is conjugated to one biotin moiety;

and the antisense strand is conjugated to one biotin moiety.

8. The composition of claim 1, wherein the sense strand is conjugated to two biotin moieties;

and the antisense strand is conjugated to one biotin moiety.

9. The composition of claim 1, wherein the antisense strand is conjugated to two biotin moieties;

and the sense strand is conjugated to one biotin moiety.

10. A method of delivering a therapeutic double-stranded RNA molecule to a cell or tissue comprising the step of

contacting the cell or tissue with a composition of claim 1.

11. A method of treating a disease in a mammal in need thereof, comprising the step of

administering to said mammal a therapeutically effective amount of a composition of claim 1.

12. The method of claim 11, wherein said disease is a bacterial infection, viral infection, or cancer.