Antibody formulations and methods

1. A pharmaceutical formulation comprising:

(a) an antibody comprising a light chain having the amino acid sequence comprising the sequence of SEQ ID NO: 5 and a heavy chain having the amino acid sequence comprising the sequence of SEQ ID NO: 10, wherein the antibody is present at a concentration of about 40 mg/ml and the antibody is in the form of a tetramer comprising two copies of the heavy chain and two copies of the light chain;

(b) citrate buffer present at a concentration of about 20 mM;

(c) trehalose present at a concentration of about 230 mM; and

(d) polysorbate 20 present at a concentration of about 0.02% by weight;

wherein the formulation is characterized by a pH of about 6.0;

wherein about indicates variation of ±5%; and

wherein at least 95% of protein appears as a single peak on high performance size exclusion chromatography after storage for at least 30 days at 38-42° C., storage for at least a year at 20-24° C., and/or storage for at least three years at 2-4° C.

2. The formulation of claim 1 , wherein the citrate buffer comprises sodium citrate dihydrate and citric acid monohydrate.

3. The formulation of claim 2 , wherein the sodium citrate dihydrate is present at a concentration within the range from about 15 mM to about 20 mM and the citric acid monohydrate is present at a concentration within the range from about 2 mM to about 6 mM.

4. The formulation of claim 1 , which is characterized by an osmolality of about 335 mOsm/kg.

5. The formulation of claim 1 , which further comprises a bulking agent.

6. The formulation of claim 1 , which is sterile.

7. The formulation of claim 1 , wherein:

(a) the antibody comprises a light chain having the amino acid sequence comprising SEQ ID NO: 29 and a heavy chain having the amino acid sequence comprising SEQ ID NO: 32 with or without the C-terminal lysine, and which is present at a concentration of about 40 mg/mL;

(b) a citrate buffer present at a concentration of 20 mM;

(c) trehalose present at a concentration of 230 mM;

(d) polysorbate 20 present at a concentration of 0.02%; and

(e) a pH of 6.0.

8. A lyophilized formulation of an antibody, comprising

(a) an antibody comprising a light chain having the amino acid sequence comprising SEQ ID NO: 5 and a heavy chain having the amino acid sequence comprising SEQ ID NO: 10 and the antibody is in the form of a tetramer comprising two copies of the heavy chain and two copies of the light chain;

(b) citrate;

(c) trehalose; and

(d) polysorbate 20.

9. The lyophilized formulation of claim 8 , which, on adding water, reconstitutes to a formulation having a pH of between about 5.5 to about 6.5.

10. The lyophilized formulation of claim 9 , wherein the formulation has a pH of about 6.0 when reconstituted.

11. The lyophilized formulation of claim 8 , comprising about 10 mg to about 40 mg of the antibody.

12. The lyophilized formulation of claim 8 , wherein the polysorbate 20 is present in an amount within the range from about 0.01% to about 0.05% by weight.

13. The lyophilized formulation of claim 8 which is reconstitutable by adding water to an aqueous solution comprising:

(a) an antibody comprising a light chain having the amino acid sequence comprising SEQ ID NO: 29 and a heavy chain having the amino acid sequence comprising SEQ ID NO: 32, with or without the C-terminal lysine, and which is present at a concentration of about 40 mg/mL;

(b) a citrate buffer present at a concentration of about 20 mM;

(c) trehalose present at a concentration of about 230 mM;

(d) polysorbate 20 present at a concentration of about 0.02%; and

(e) a pH of about 6.0.

14. The lyophilized formulation of claim 13 , wherein the lyophilized formulation comprises about 200 mg of the antibody and enables reconstitution with sterile water.

15. The lyophilized formulation of claim 8 , comprising:

(a) 200 mg of the antibody;

(b) 25 mg of sodium citrate dihydrate;

(c) 2.15 mg citric acid monohydrate;

(d) 435 mg trehalose dihydrate; and

(e) 1 mg polysorbate 20.

16. A pharmaceutical product, comprising:

(a) a vial comprising in powder form:

(i) about 200 mg antibody;

(ii) about 25 mg sodium citrate dehydrate;

(iii) about 2.15 mg citric acid monohydrate;

(iv) about 435 mg trehalose dehydrate; and

(v) about 1 mg polysorbate 20;

(b) instructions for reconstitution of the antibody; and

(c) instructions for preparing the reconstituted antibody for infusion,

wherein:

(i) the antibody comprises a light chain having the amino acid sequence comprising SEQ ID NO: 29 and a heavy chain having the amino acid sequence comprising SEQ ID NO: 32, with or without the C-terminal lysine; and

(ii) the reconstitution instructions require initial reconstitution with water to a volume of about 5 mL.

17. The formulation of claim 1 , wherein:

(a) the antibody comprises a light chain having the amino acid sequence comprising SEQ ID NO: 29 and a heavy chain having the amino acid sequence comprising SEQ ID NO: 31 with or without the C-terminal lysine, and which is present at a concentration of about 40 mg/mL;

(b) a citrate buffer present at a concentration of about 20 mM;

(c) trehalose present at a concentration of about 230 mM;

(d) polysorbate 20 present at a concentration of about 0.02%; and

(e) a pH of about 6.0.

18. The lyophilized formulation of claim 8 which is reconstitutable by adding water to an aqueous solution comprising:

(a) an antibody comprising a light chain having the amino acid sequence comprising SEQ ID NO: 29 and a heavy chain having the amino acid sequence comprising SEQ ID NO: 31, with or without the C-terminal lysine, and which is present at a concentration of about 40 mg/mL;

(b) a citrate buffer present at a concentration of about 20 mM;

(c) trehalose present at a concentration of about 230 mM;

(d) polysorbate 20 present at a concentration of about 0.02%; and

(e) a pH of about 6.0.

19. The lyophilized formulation of claim 8 , comprising about 40 mg to about 1000 mg of the antibody.

20. The lyophilized formulation of claim 8 , comprising:

(a) 200 mg of the antibody;

(b) 25 mg of sodium citrate dihydrate;

(c) 3.15 mg citric acid monohydrate;

(d) 435 mg trehalose dihydrate; and

(e) 1 mg polysorbate 20.

21. A pharmaceutical product, comprising:

(a) a vial comprising in powder form:

(i) about 200 mg antibody;

(ii) about 25 mg sodium citrate dehydrate;

(iii) about 3.15 mg citric acid monohydrate;

(iv) about 435 mg trehalose dehydrate; and

(v) about 1 mg polysorbate 20;

(b) instructions for reconstitution of the antibody; and

(c) instructions for preparing the reconstituted antibody for infusion,

wherein:

(i) the antibody comprises a light chain having the amino acid sequence comprising SEQ ID NO: 29 and a heavy chain having the amino acid sequence comprising SEQ ID NO: 32, with or without the C-terminal lysine; and

(ii) the reconstitution instructions require initial reconstitution with water to a volume of about 5 mL.

22. The formulation of claim 1 , wherein less than about 5% of the antibody is present as an aggregate in the formulation.

23. The formulation of claim 1 consisting essentially of the antibody, citrate buffer, trehalose and polysorbate.