Polyalkylene oxides having hindered ester-based biodegradable linkers

1. A compound of the Formula (I)

wherein:

A is

R 1 is a polyethylene glycol;

L 1 and L′ 1 are each —NH(CH 2 ) 4 —, wherein —NH is connected to L 2 ;

L 2 and L′ 2 are each —(CH 2 ) 2 —O—C(O)—, wherein —(CH 2 ) 2 is connected to R 1 ;

Y 1 and Y′ 1 are independently O;

R 2 , R′ 2 , R 3 , and R′ 3 are independently C 1-6 alkyl;

R 4 and R′ 4 are independently biologically active moieties containing a hydroxyl moiety to form an ester; and

(p) and (p′) are independently an integer from about 1 to about 3.

2. The compound of claim 1 , wherein the biologically active moiety is selected from the group consisting of pharmaceutically active compounds, enzymes, proteins, antibodies, monoclonal antibodies, single chain antibodies and peptides.

3. The compound of claim 1 , wherein -L 1 -C(R 2 )(R 3 )—C(═Y 1 )— and -L′ 1 —C(R′ 2 )(R′ 3 )—C(═Y′ 1 )— are independently

4. The compound of claim 1 having Formula (II)

5. The compound of claim 1 , wherein R 1 comprises a linear, terminally branched or multi-armed polyethylene glycol.

6. The compound of claim 5 , wherein the polyethylene glycol is selected from the group consisting of

—Y 71 —(CH 2 CH 2 O) n —CH 2 CH 2 Y 71 —,

—Y 71 —(CH 2 CH 2 O) n —CH 2 C(═Y 72 )—Y 71 —,

—Y 71 —C(═Y 72 )—(CH 2 ) a71 —Y 73 —(CH 2 CH 2 O) n —CH 2 CH 2 —Y 73 —(CH 2 ) a71 —C(═Y 72 )—Y 71 —, and

—Y 71 —(CR 71 R 72 ) a72 —Y 73 —(CH 2 ) b71 —O—(CH 2 CH 2 O) n —(CH 2 ) b71 —Y 73 —(CR 71 R 72 ) a72 —Y 71 —,

wherein:

Y 71 and Y 73 are independently O, S, SO, SO 2 , NR 73 or a bond;

Y 72 is O, S, or NR 74 ;

R 71-74 are independently the same moieties which can be used for R 2 ;

(a71), (a72), and (b71) are independently zero or a positive integer; and

(n) is an integer from about 10 to about 2300.

7. The compound of claim 5 , wherein the polyethylene glycol has the formula, —O—(CH 2 CH 2 O) n —

wherein (n) is an integer from about 10 to about 2,300.

8. The compound of claim 1 , wherein R 1 has an average molecular weight from about 2,000 to about 100,000 daltons.

9. The compound of claim 1 , wherein R 1 has an average molecular weight of from about 5,000 to about 60,000 daltons.

10. The compound of claim 1 , wherein R 1 has an average molecular weight from about 5,000 to about 25,000 daltons or from about 20,000 to about 45,000 daltons.

11. The compound of claim 1 wherein R 2 , R′ 2 , R 3 and R′ 3 are independently selected from the group consisting of methyl, ethyl and isopropyl.

12. A compound selected from the group consisting of:

wherein:

R 4 is a biologically active moiety;

(z) is a positive integer from about 1 to about 10;

(z′) is zero or a positive integer from about 1 to about 4;

PEG has the formula —O(CH 2 CH 2 O) n —; and

(n) is a positive integer from about 10 to about 2,300.

13. A compound selected from the group consisting of:

wherein:

drug is pharmaceutically active compounds, enzymes, proteins, antibodies, monoclonal antibodies, single chain antibodies and peptides;

(z) is a positive integer from about 1 to about 10;

(z′) is zero or a positive integer from about 1 to about 4;

PEG has the formula —O(CH 2 CH 2 O) n —; and

(n) is a positive integer from about 10 to about 2,300.