Pharmaceutical compositions and methods for delivering such compositions

View Patent ↗

Loading inventors, assignments & file history…

Monitor This Case

Get email alerts when status or documents change.

Order Certified Copies

Most orders are placed with the USPTO same day — all within 24 business hours.

Order via The Patent Place →

Pre-filled with this patent's details

Quick Facts

Patent No.: US 8,435,505
App. No.: 13/525,068
Granted: May 7, 2013
Kind: B2

External Links

USPTO Patent Center↗ Full Patent PDF↗

Abstract

The present invention provides pharmaceutical compositions comprising a pharmaceutically acceptable excipient and a conjugate having a degradable linkage. The conjugates include at least one of each the following: an aromatic moiety comprising an ionizable hydrogen atom, a spacer moiety, and a water-soluble polymer. Methods for delivering such compositions are also provided.

Claims (39)

1. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a conjugate of the following formula:

wherein:

POLY 1 is a first water-soluble polymer;

POLY 2 is a second water-soluble polymer;

X 1 is a first spacer moiety;

X 2 is a second spacer moiety;

H α is an ionizable hydrogen atom;

R 1 is H or an organic radical;

R 2 is H or an organic radical; and

Y 1 is O or S;

Y 2 is O or S; and

D is a residue of a biologically active agent.

2. The pharmaceutical composition of claim 1 , wherein each of POLY 1 and POLY 2 is a poly(ethylene glycol).

3. The pharmaceutical composition of claim 2 , wherein each poly(ethylene glycol) has a weight-average molecular weight in the range of from about 120 Daltons to about 6,000 Daltons.

4. The pharmaceutical composition of claim 2 , wherein each poly(ethylene glycol) has a weight-average molecular weight in the range of from about 6,000 Daltons to about 100,000 Daltons.

5. The pharmaceutical composition of claim 1 wherein the first spacer moiety is selected from the group consisting of —C(O)—NH—CH 2 —CH 2 —, —CH 2 —CH 2 —NH—C(O)—, —C(O)—NH—CH 2 —CH 2 —CH 2 —, —CH 2 —CH 2 —CH 2 —NH—C(O)—, —C(O)—NH—CH 2 —CH 2 —CH 2 —CH 2 —, —CH 2 —CH 2 —CH 2 —CH 2 —NH—C(O)—, —C(O)—NH—, —NH—C(O)—, —C(O)—NH—CH 2 —CH 2 —CH 2 —CH 2 —CH 2 —, —CH 2 —CH 2 —CH 2 —CH 2 —CH 2 —NH—C(O)—, —NH—C(O)—CH 2 —CH 2 —, —CH 2 —CH 2 —C(O)—NH—, —NH—C(O)—CH 2 —CH 2 —CH 2 —, —CH 2 —CH 2 —CH 2 —C(O)—NH—, —NH—C(O)—CH 2 —CH 2 —CH 2 —CH 2 —, —CH 2 —CH 2 —CH 2 —CH 2 —C(O)—NH—, —NH—C(O)—CH 2 —CH 2 —CH 2 —CH 2 —CH 2 —, —CH 2 —CH 2 —CH 2 —CH 2 —CH 2 —C(O)—NH—, —NH—C(O)—CH 2 —CH 2 —C(O)—, —C(O)—CH 2 —CH 2 —C(O)—NH—, —NH—C(O)—CH 2 —CH 2 —CH 2 —C(O)—, —C(O)—CH 2 —CH 2 —CH 2 —C(O)—NH—, —NH—C(O)—CH 2 —CH 2 —CH 2 —CH 2 —C(O)—, —C(O)—CH 2 —CH 2 —CH 2 —CH 2 —C(O)—NH—, —NH—C(O)—CH 2 —CH 2 —CH 2 —CH 2 —CH 2 —C(O)—, —C(O)—CH 2 —CH 2 —CH 2 —CH 2 —CH 2 —C(O)—NH—, —C(O)—CH 2 —CH 2 —, —CH 2 —CH 2 —C(O)—, —C(O)—CH 2 —CH 2 —CH 2 —, —CH 2 —CH 2 —CH 2 —C(O)—, —C(O)—CH 2 —CH 2 —CH 2 —CH 2 —, —CH 2 —CH 2 —CH 2 —CH 2 —C(O)—, —C(O)—CH 2 —CH 2 —CH 2 —CH 2 —CH 2 —, —CH 2 —CH 2 —CH 2 —CH 2 —CH 2 —C(O)—, —NH—CH 2 —CH 2 —(OCH 2 CH 2 ) 1-3 —NH—C(O)—, —C(O)—NH—(CH 2 CH 2 O) 1-3 —CH 2 —CH 2 —NH—, —C(O)—NH—CH 2 —CH 2 —(OCH 2 CH 2 ) 1-3 —NH—C(O)—, —C(O)—NH—(CH 2 CH 2 O) 1-3 —CH 2 —CH 2 —NH—C(O)—, —NH—C(O)—CH 2 —, —CH 2 —C(O)—NH—, —NH—C(O)—CH 2 —O—, —O—CH 2 —C(O)—NH—, —CH 2 —CH 2 —NH—C(O)—CH 2 —CH 2 —CH 2 —C(O)—NH—, —NH—C(O)—CH 2 —CH 2 —CH 2 —C(O)—NH—CH 2 —CH 2 —, —O—CH 2 —CH 2 —NH—C(O)—CH 2 —CH 2 —CH 2 —C(O)—NH—, —NH—C(O)—CH 2 —CH 2 —CH 2 —C(O)—NH—CH 2 —CH 2 —O—, —C(O)—NH—CH 2 —CH 2 —, —CH 2 —CH 2 —NH—C(O)—, —C(O)—NH—CH 2 —CH 2 —O—, and —O—CH 2 —CH 2 —NH—C(O)—, and the second spacer moiety is selected from the group consisting of —C(O)—NH—CH 2 —CH 2 —, —CH 2 —CH 2 —NH—C(O)—, —C(O)—NH—CH 2 —CH 2 —CH 2 —, —CH 2 —CH 2 —CH 2 —NH—C(O)—, —C(O)—NH—CH 2 —CH 2 —CH 2 —CH 2 —, —CH 2 —CH 2 —CH 2 —CH 2 —NH—C(O)—, —C(O)—NH—, —NH—C(O)—, —C(O)—NH—CH 2 —CH 2 —CH 2 —CH 2 —CH 2 —, —CH 2 —CH 2 —CH 2 —CH 2 —CH 2 —NH—C(O)—, —NH—C(O)—CH 2 —CH 2 —, —CH 2 —CH 2 —C(O)—NH—, —NH—C(O)—CH 2 —CH 2 —CH 2 —, —CH 2 —CH 2 —CH 2 —C(O)—NH—, —NH—C(O)—CH 2 —CH 2 —CH 2 —CH 2 —, —CH 2 —CH 2 —CH 2 —CH 2 —C(O)—NH—, —NH—C(O)—CH 2 —CH 2 —CH 2 —CH 2 —CH 2 —, —CH 2 —CH 2 —CH 2 —CH 2 —CH 2 —C(O)—NH—, —NH—C(O)—CH 2 —CH 2 —C(O)—, —C(O)—CH 2 —CH 2 —C(O)—NH—, —NH—C(O)—CH 2 —CH 2 —CH 2 —C(O)—, —C(O)—CH 2 —CH 2 —CH 2 —C(O)—NH—, —NH—C(O)—CH 2 —CH 2 —CH 2 —CH 2 —C(O)—, —C(O)—CH 2 —CH 2 —CH 2 —CH 2 —C(O)—NH—, —NH—C(O)—CH 2 —CH 2 —CH 2 —CH 2 —CH 2 —C(O)—, —C(O)—CH 2 —CH 2 —CH 2 —CH 2 —CH 2 —C(O)—NH—, —C(O)—CH 2 —CH 2 —, —CH 2 —CH 2 —C(O)—, —C(O)—CH 2 —CH 2 —CH 2 —, —CH 2 —CH 2 —CH 2 —C(O)—, —C(O)—CH 2 —CH 2 —CH 2 —CH 2 —, —CH 2 —CH 2 —CH 2 —CH 2 —C(O)—, —C(O)—CH 2 —CH 2 —CH 2 —CH 2 —CH 2 —, —CH 2 —CH 2 —CH 2 —CH 2 —CH 2 —C(O)—, —NH—CH 2 —CH 2 —(OCH 2 CH 2 ) 1-3 —NH—C(O)—, —C(O)—NH—(CH 2 CH 2 O) 1-3 —CH 2 —CH 2 —NH—, —C(O)—NH—CH 2 —CH 2 —(OCH 2 CH 2 ) 1-3 —NH—C(O)—, —C(O)—NH—(CH 2 CH 2 O) 1-3 —CH 2 —CH 2 —NH—C(O)—, —NH—C(O)—CH 2 —, —CH 2 —C(O)—NH—, —NH—C(O)—CH 2 —O—, —O—CH 2 —C(O)—NH—, —CH 2 —CH 2 —NH—C(O)—CH 2 —CH 2 —CH 2 —C(O)—NH—, —NH—C(O)—CH 2 —CH 2 —CH 2 —C(O)—NH—CH 2 —CH 2 —, —O—CH 2 —CH 2 —NH—C(O)—CH 2 —CH 2 —CH 2 —C(O)—NH—, —NH—C(O)—CH 2 —CH 2 —CH 2 —C(O)—NH—CH 2 —CH 2 —O—, —C(O)—NH—CH 2 —CH 2 —, —CH 2 —CH 2 —NH—C(O)—, —C(O)—NH—CH 2 —CH 2 —O—, and —O—CH 2 —CH 2 —NH—C(O)—.

6. The pharmaceutical composition of claim 1 , wherein R 1 is H and R 2 is H.

7. The pharmaceutical composition of claim 1 , wherein Y 1 is O and Y 2 is O.

8. The pharmaceutical composition of claim 1 , wherein the biologically active agent is a polypeptide.

9. The pharmaceutical composition of claim 1 , wherein the conjugate corresponds to the following formula: