Claims for Patent: 8,754,195

Summary for Patent: 8,754,195

Title:	Antibody formulations
Abstract:	The present invention relates to formulations comprising sucrose, and methods of making such formulations, wherein the sucrose content promotes the reduction or elimination of the reversible self-association (RSA) tendency of the antibody in the formulation. The present invention also relates to formulations comprising an anti-PDGFR-alpha antibody or antibody fragment. Such antibodies can be used in various methods of treatment. The application further relates to a method of eliminating or reducing the RSA tendency of antibodies in a formulation.
Inventor(s):	Dimitrova; Mariana N. (Frederick, MD), Mody; Neil (Clarksburg, MD)
Assignee:	MedImmune, LLC (Gaithersburg, MD)
Application Number:	13/175,522
Patent Claims:	1. A formulation, comprising: a) an aqueous carrier; b) 1 mg/ml to 100 mg/ml of an antibody or antibody fragment that specifically binds to PDGFR-alpha and inhibits growth of cells that express PDGFR-alpha, wherein said antibody or antibody fragment in said formulation has substantially similar reversible self-association (RSA) characteristics at 2-8.degree. C. and 23-27.degree. C., as determined by analytical ultracentrifugation (AUC); c) 4% to 20% (weight/volume) sucrose; d) 0.01% to 0.1% (weight/volume) polysorbate 80 (PS80); and e) sodium-acetate buffer, wherein said formulation has a pH of pH 4.0 to pH 6.0. 2. The formulation of claim 1, wherein said antibody or antibody fragment is present at a concentration of from 20 mg/ml to 50 mg/ml. 3. The formulation of claim 1, wherein the antibody or antibody fragment comprises a VH CDR1 having the amino acid sequence of SEQ ID NO: 3; a VH CDR2 having the amino acid sequence of SEQ ID NO: 4; a VH CDR3 having the amino acid sequence of SEQ ID NO: 5: a VL CDR1 having the amino acid sequence of SEQ ID NO: 6; a VL CDR2 having the amino acid sequence of SEQ ID NO: 7; and a VL CDR3 having the amino acid sequence of SEQ ID NO: 8. 4. The formulation of claim 1, comprising 10% (w/v) sucrose. 5. The formulation of claim 1, wherein the formulation is substantially free of histidine. 6. The formulation of claim 1, wherein the formulation is substantially free of any additional surfactant. 7. The formulation of claim 1, wherein the formulation is substantially free of any additional saccharide or polyol. 8. A formulation, consisting essentially of: a) sterile water; b) 20 mg/ml of an antibody or antibody fragment that specifically binds to PDGFR-alpha and inhibits growth of cells that express PDGFR-alpha; c) 10% (weight/volume) sucrose; d) 0.05% (weight/volume) polysorbate 80 (PS80); and e) 50 mM sodium-acetate buffer, wherein said formulation has a pH of pH 5.5. 9. The formulation of claim 8, wherein the antibody or antibody fragment comprises a VH CDR1 having the amino acid sequence of SEQ ID NO: 3; a VH CDR2 having the amino acid sequence of SEQ ID NO: 4; a VH CDR3 having the amino acid sequence of SEQ ID NO: 5: a VL CDR1 having the amino acid sequence of SEQ ID NO: 6; a VL CDR2 having the amino acid sequence of SEQ ID NO: 7; and a VL CDR3 having the amino acid sequence of SEQ ID NO: 8. 10. The formulation of claim 8, wherein the formulation is not suitable for lyophilization. 11. A formulation, comprising: a) an aqueous carrier; b) 1 mg/ml to 100 mg/ml of an antibody or antibody fragment; c) 4% to 20% (weight/volume) sucrose; d) 0.01% to 0.1% (weight/volume) polysorbate 80 (PS80); and e) sodium-acetate buffer, wherein said formulation has a pH of pH 4.0 to pH 6.0, and wherein said antibody or antibody fragment in said formulation has substantially the same non-RSA tendency when evaluated at about 2-8.degree. C. versus at about 23-27.degree. C. 12. A formulation, comprising: a) an aqueous carrier; b) 1 mg/ml to 100 mg/ml of an antibody or antibody fragment; c) 4% to 20% (weight/volume) sucrose; d) 0.01% to 0.1% (weight/volume) polysorbate 80 (PS80); and e) sodium-acetate buffer, wherein said formulation has a pH of pH 4.0 to pH 6.0, and wherein greater than 95% of said antibody or antibody fragment in said formulation is in non-self-associated, monomeric form at 2-8.degree. C. 13. A formulation comprising an antibody or antibody fragment produced according to a method for eliminating or reducing reversible self-association (RSA) of an antibody in a formulation, said method comprising providing an initial formulation comprising the antibody or antibody fragment, wherein RSA of said antibody or antibody fragment in said initial formulation is measurable by HPSEC (i) at approximately 2-8.degree. C. and/or (ii) at a concentration of greater than 4 mg/ml, and which antibody or antibody fragment in said initial formulation contains high molecular weight forms; adding sucrose to said initial formulation to provide an altered formulation having about 4% to about 20% (weight/volume) sucrose, wherein RSA of the antibody or antibody fragment in the altered formulation is eliminated or reduced relative to that of the initial formulation, when compared at a given antibody concentration at approximately 2-8.degree. C. 14. The formulation of claim 1, comprising 6% to 12% (w/v) sucrose.

Details for Patent 8,754,195

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Merck Sharp & Dohme Corp.	ZOSTAVAX	zoster vaccine live	For Injection	125123	05/25/2006		2030-07-02