Methods for Inhibiting Yellow Color Formation in a Composition

• US 20120183531A1
• Filed: 07/13/2010
• Published: 07/19/2012
• Est. Priority Date: 07/14/2009
• Status: Abandoned Application

• Current Assignee: Biogen MA Inc. (Biogen, Inc.)
• Original Assignee: Biogen Idec MA Inc. (Biogen, Inc.)
• Inventors: Maloney, Kevin, Lucas, Karin
• Application Number:
  US13/384,178
• Publication Number:
  US 20120183531A1
• Time in Patent Office: Days
• US Class Current: 424/130.1
• CPC Class Codes: A61K 39/39591 Stabilisation, fragmentation
• CPC Class Codes: A61K 47/183 Amino acids, e.g. glycine, EDTA or aspartame
• CPC Class Codes: A61K 47/20 containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: C07K 16/00 Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies antibodies with enzymatic activity, e.g. abzymes C12N9/0002
• CPC Class Codes: Y10T 436/147777 Plural nitrogen in the same ring [e.g., barbituates, creatinine, etc.]

Abstract

The present invention is related to methods for preventing or retarding (i.e., inhibiting) yellow color or peroxide formation in a composition. The present invention is also related to methods of reducing or decreasing the amount of yellow color or peroxide in a composition. More specifically, the present invention relates to the use of an antioxidant, an oxygen scavenger, pH, a chelating agent, and/or at least two factors in the methods of the invention. The present invention is also related to methods for predicting the rate of yellow color or peroxide formation in a composition.

Claims

1. A method for preventing or retarding yellow color or peroxide formation in a composition, wherein the method comprises use of an antioxidant or oxygen scavenger in said composition, wherein said composition comprises a solution or formulation selected from the group consisting of:

a) a buffer solution;

b) a protein formulation;

c) a solution containing a protein; and

d) a solution containing an antibody.

3. The method of claim 1, wherein said composition comprises a compound selected from the group consisting of:

a) histidine;

b) citrate;

c) phosphate;

d) succinate;

e) acetate;

f) Tris; and

g) any combination of two or more of a, b, c, d, e, and f.

5. The method of claim 1, wherein said composition comprises an excipient, wherein said excipient is selected from the group consisting of:

a) a polysorbate compound;

b) polysorbate 20;

c) polysorbate 80;

d) NaCl;

e) sucrose;

f) glycerol;

g) arginine;

h) glycine;

i) trehalose;

j) mannitol;

k) xylitol;

l) lactose;

m) sorbitol;

n) a poloxamer;

o) a glycol;

p) CaCl₂;

q) imidazole;

r) benzyl alcohol;

s) urea;

t) leucine;

u) isoleucine;

v) threonine;

w) glutamate or glutamic acid;

x) phenylalanine;

y) cresol; and

z) any combination of two or more of a through y.

6. The method of claim 1, wherein said antioxidant or oxygen scavenger is selected from the group consisting of:

a) methionine;

b) ascorbic acid;

c) glutathione;

d) Vitamin A;

e) Vitamin E;

f) selenium;

g) retinyl palmitate;

h) cysteine;

i) sodium sulfite;

j) thioglycerol;

k) thioglycolic acid;

l) metabisulfite; and

m) any combination of two or more of a through l.

8. The method of claim 1, wherein the concentration of said antioxidant or oxygen scavenger is selected from the group consisting of:

a) about 0.0001 mM to about 10000 mM;

b) about 0.001 mM to about 1000 mM;

c) about 0.01 mM to about 100 mM; and

d) about 0.1 mM to about 10 mM.

9. The method of claim 1, wherein said composition further comprises a chelating agent.

10. The method of claim 9, wherein said chelating agent is selected from the group consisting of:

a) EDTA (ethylenediaminetetraacetic acid);

b) EGTA (ethyleneglycoltetraacetic acid);

c) ascorbic acid;

d) iminodiacetate;

e) tetrasodium iminodisuccinate;

f) citric acid;

g) dicarboxymethylglutamic acid;

h) EDDS (ethylenediaminedisuccinic acid);

i) DTPMP.Na (hepta sodium salt of diethylene triamine penta or methylene phosphonic acid);

j) malic acid;

k) NTA (nitrilotriacetic acid);

l) a nonpolar amino acid;

m) methioninie;

n) oxalic acid;

o) phosphoric acid;

p) a polar amino acid;

q) arginine;

r) asparagine;

s) aspartic acid;

t) glutamic acid;

u) glutamine;

v) lysine;

w) ornithine;

x) a siderophore;

y) Desferrioxamine B;

z) succinic acid;

aa) hydrolysed wool;

bb) a chelating resin; and

cc) a CHELEX®

resin.

11. The method of claim 1, further comprising decreasing exposure of said composition to oxygen, wherein said decreasing exposure is performed by a means selected from the group consisting of:

a) reducing the headspace gas content between the surface of the composition and a container closure;

b) reducing ambient oxygen content;

a) overlaying the composition with nitrogen;

d) sparging the composition with nitrogen, and

e) any combination of a, b, c, or d.

14. The method of claim 1, further comprising adjusting the pH of said composition, wherein the adjusted pH is other than about pH 6.0.

15. The method of claim 1, further comprising adjusting the pH of said composition, wherein the adjusted pH is selected from the group consisting of:

a) about 7.5 to about 7.0;

b) about 7.0 to about 6.5;

c) about 6.0 or less;

d) about 5.5 or less; and

e) about 5.0 or less.

16. The method of claim 1, further comprising use of container coloration and/or packaging to protect said composition from light.

2. A method of reducing or decreasing the amount of yellow color or peroxide in a composition, wherein the method comprises use of an antioxidant or oxygen scavenger in said composition, wherein said composition comprises a solution or formulation selected from the group consisting of:

a) a buffer solution;

b) a protein formulation;

c) a solution containing a protein; and

d) a solution containing an antibody.

22. The method of claim 2, wherein said reduction or decrease in the amount of yellow color in a composition is measured as a percent decrease in b* value.

4. (canceled)

7. (canceled)

12. (canceled)

13. (canceled)

17. (canceled)

18. A method for preventing or retarding yellow color or peroxide formation in a composition, the method comprising use of at least two factors to prevent or retard yellow color or peroxide formation, wherein said composition is selected from the group consisting of:

a) a buffer solution;

b) a protein formulation;

c) a solution containing a protein; and

d) a solution containing an antibody.

20. The method of claim 18, wherein said use of at least two factors comprises use of any combination of two or more factors selected from the group consisting of:

a) methionine;

b) decreased oxygen exposure;

c) NaCl;

d) a polysorbate compound;

e) polysorbate 20;

f) polysorbate 80;

g) arginine;

h) a pH of about 5.0;

i) a pH of about 5.5;

j) a pH of about 6.0;

k) a pH of about 6.5; and

l) a pH of about 7.0.

21. The method of either claim 18, wherein said use of at least two factors comprises use of one or more combinations selected from the group consisting of:

a) methionine and decreased oxygen exposure;

b) methionine and a pH of about 5;

c) methionine and a pH of about 6;

d) NaCl and polysorbate 80; and

e) arginine and a pH of about 7.

19. A method of reducing or decreasing the amount of yellow color or peroxide in a composition, wherein the method comprises use of at least two factors to reduce or decrease yellow color or peroxide formation, wherein said composition is selected from the group consisting of:

a) a buffer solution;

b) a protein formulation;

c) a solution containing a protein; and

d) a solution containing an antibody.

23. (canceled)

24. A method for predicting or determining the rate of yellow color or peroxide formation in a composition, wherein said composition comprises a solution or formulation selected from the group consisting of:

a) a buffer solution;

b) a protein formulation;

c) a solution containing a protein; and

d) a solution containing an antibody

and wherein the predicting or determining comprises the steps of incubating the composition at a specified range of temperatures, quantitating the amount of yellow color or peroxide formed as a function of time and temperature, and extrapolating a prediction or determination of the rate of yellow color or peroxide formation in said composition for any temperature inside or outside the specified range of temperatures.

25. The method of claim 24, wherein the method further comprises the steps of preparing a range of concentrations of the composition and extrapolating a prediction or determination of the rate of yellow color or peroxide formation in said composition for any concentration inside or outside the specified range of concentrations.

26. The method of claim 24, wherein said composition comprises a compound selected from the group consisting:

a) histidine;

b) citrate;

c) phosphate;

d) succinate;

e) Tris;

f) acetate; and

g) any combination of two or more of a, b, c, d, e, and f.

27. The method of claim 24, wherein the rate of yellow color or peroxide formation in said composition is predicted or determined as a function of composition storage temperature.

29. The method of claim 24, wherein the prediction or determination is calculated based on a two-factor interaction.

28. (canceled)

30. (canceled)