Dendrimer-based excipients for the attenuation of protein aggregation

Patent metadata

Field	Value
Publication number	US-9410142-B2
Application number	US-201113884420-A
Country	US
Kind code	B2
Filing date	Nov 11, 2011
Priority date	Nov 11, 2010
Publication date	Aug 9, 2016
Grant date	Aug 9, 2016

Abstract

One aspect of the invention is a salt comprising guanidinium groups, as shown in formula I. Another aspect of the invention is a salt comprising guanidinium groups, as shown in formula II. Another aspect of the invention is a salt comprising guanidinium groups, as shown in formula III. Another aspect of the invention is a salt comprising guanidinium groups, as shown in formula IV. Yet another aspect of the invention is a salt comprising guanidinium groups, as shown in formula I, II, III, and IV further comprising independently for each occurrence citrate, phosphate, or sulfate anion. Also disclosed are compositions comprising a protein and a salt comprising guanidinium groups, as shown in formula I, II, III, and IV. Also provided are methods of increasing shelf life of an aqueous solution of a protein and decreasing the amount of protein aggregation in an aqueous solution of a protein.

First claim

We claim:

1. A salt, comprising a plurality of anions; and a cation represented by formula I:

wherein, independently for each occurrence,
each anion is

Z is —CH 2 CH 2 —, —CH 2 CH 2 CH 2 —, —CH 2 CH 2 CH 2 CH 2 —, or —CH 2 CH 2 CH 2 CH 2 CH 2 —;
Y is —CH 2 —, —CH 2 CH 2 —, —CH 2 CH 2 CH 2 —, —CH 2 CH 2 CH 2 CH 2 —, or —CH 2 CH 2 CH 2 CH 2 CH 2 —;
X 1 is

X 2 is

and
X 3 is

2. A salt, comprising a plurality of anions; and a cation represented by formula II:

wherein, independently for each occurrence,
each anion is

Z is —CH 2 CH 2 —, —CH 2 CH 2 CH 2 —, —CH 2 CH 2 CH 2 CH 2 —, or —CH 2 CH 2 CH 2 CH 2 CH 2 —;
Y is —CH 2 —, —CH 2 CH 2 —, —CH 2 CH 2 CH 2 —, —CH 2 CH 2 CH 2 CH 2 —, or —CH 2 CH 2 CH 2 CH 2 CH 2 —;
X 1 is

X 2 is

and
X 3 is

3. A salt, comprising a plurality of anions; and a cation represented by formula III:

wherein, independently for each occurrence,
each anion is

X 1 is

X 2 is

X 3 is

 and
X 4 is

4. A salt, comprising a plurality of anions; and a cation represented by formula IV:

wherein, independently for each occurrence,
each anion is

Z is —CH 2 CH 2 —, —CH 2 CH 2 CH 2 —, —CH 2 CH 2 CH 2 CH 2 —, or —CH 2 CH 2 CH 2 CH 2 CH 2 —;
X 1 is

X 2 is

X 3 is

 and
X 4 is

5. The salt of claim 1 , wherein X 1 is

6. The salt of claim 1 , wherein X 1 is

and X 2 is

7. The salt of claim 1 , wherein X 1 is

and X 2 is

8. The salt of claim 1 , wherein Z is —CH 2 CH 2 —.

9. The salt of claim 1 , wherein Y is —CH 2 CH 2 —.

10. The salt of claim 1 , wherein Y is —CH 2 CH 2 —; and Z is —CH 2 CH 2 —.

11. The salt of claim 1 , wherein each anion is

12. The salt of claim 1 , wherein each anion is

13. The salt of claim 1 , wherein each anion is

14. A composition, comprising a protein; and a salt of claim 1 .

15. The composition of claim 14 , wherein the protein is selected from the group consisting of antibodies and enzymes.

16. A method of increasing shelf life of an aqueous solution of a protein, comprising:
combining an aqueous solution of a protein and an effective amount of a salt of claim 1 .

17. The method of claim 16 , wherein the protein is selected from the group consisting of antibodies and enzymes.

18. A method of decreasing the amount of protein aggregation in an aqueous solution of a protein, comprising:
combining an aqueous solution of a protein and an effective amount of a salt of claim 1 .

19. The method of claim 18 , wherein the protein is selected from the group consisting of antibodies and enzymes.

Assignees

• Trout Ii Bernhardt L
• Shukla Diwakar
• Schneider Curtiss P
• Massachusetts Inst Technology

Inventors

• Trout Ii Bernhardt L
• Shukla Diwakar
• Schneider Curtiss P

Classifications

• C12N9/96 Primary

  Stabilising an enzyme by forming an adduct or a composition; Forming enzyme conjugates · CPC title

• C07C279/12

  being further substituted by nitrogen atoms not being part of nitro or nitroso groups · CPC title