Claims for Patent: 8,883,146

Summary for Patent: 8,883,146

Title:	Protein formulations and methods of making same
Abstract:	The invention provides an aqueous formulation comprising water and a protein, and methods of making the same. The aqueous formulation of the invention may be a high protein formulation and/or may have low levels of conductity resulting from the low levels of ionic excipients. Also included in the invention are formulations comprising water and proteins having low osmolality.
Inventor(s):	Fraunhofer; Wolfgang (Gurnee, IL), Bartl; Annika (Ludwigshafen, DE), Krause; Hans-Juergen (Biblis, DE), Tschoepe; Markus (Hessheim, DE), Kaleta; Katharina (Ludwigshafen, DE)
Assignee:	AbbVie Inc. (North Chicago, IL)
Application Number:	13/774,735
Patent Claims:	1. An aqueous formulation comprising an antibody, or antigen-binding fragment thereof, at a concentration of at least 50 mg/ml, a non-ionizable excipient, a buffer, and water, wherein the formulation has a conductivity of less than about 2.5 mS/cm, and the antibody, or antigen-binding fragment thereof, has a molecular weight (Mw) greater than about 47 kDa. 2. The formulation of claim 1, wherein the antibody, or antigen-binding fragment thereof, is selected from the group consisting of a chimeric antibody, a human antibody, a humanized antibody, and a domain antibody (dAb). 3. The formulation of claim 1, wherein the antibody, or antigen-binding fragment thereof, is an anti-tumor necrosis factor alpha (TNF.alpha.) antibody or an anti-interleukin-12 (IL-12) antibody. 4. The formulation of claim 1, wherein the antibody, or antigen-binding fragment thereof, is selected from the group consisting of adalimumab, alemtuzumab, Arcitumomab, cetuximab, trastuzumab, imciromab pentetate, capromab pendetide, infliximab, abciximab, rituximab, basiliximab, palivizumab, nofetumomab, omalizumab, daclizumab, ibritumomab tiuxetan, muromonab-CD3, edrecolomab, gemtuzumab ozogamicin, golimumab, certolizumab pegol, eculizumab, ustekinumab, panitumumab, tositumomab and I131 tositumomab, and bevacizumab. 5. The formulation of claim 1, wherein the concentration of the antibody, or antigen-binding fragment thereof, is 50 to 200 mg/ml. 6. The formulation of claim 1, wherein the non-ionizable excipient is a sugar or a polysorbate. 7. A device comprising the formulation of claim 1. 8. An article of manufacture comprising the device of claim 7. 9. An aqueous formulation comprising an antibody, or antigen-binding fragment thereof, at a concentration of at least 50 mg/ml, a non-ionizable excipient, a buffer, and water, wherein the formulation has a conductivity of less than about 2.5 mS/cm, wherein the antibody, or antigen-binding fragment thereof, has a light chain variable region (LCVR) having a CDR3 domain comprising the amino acid sequence of SEQ ID NO:3, a CDR2 domain comprising the amino acid sequence of SEQ ID NO:5, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 7, and a heavy chain variable region (HCVR) having a CDR3 domain comprising the amino acid sequence of SEQ ID NO:4, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 6, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO:8. 10. The formulation of claim 9, wherein the antibody, or antigen-binding portion thereof, has an LCVR comprising the amino acid sequence set forth in SEQ ID NO: 1, and an HCVR comprising the amino acid sequence set forth in SEQ ID NO: 2. 11. The formulation of claim 10, wherein the antibody, or antigen-binding portion thereof, is adalimumab. 12. The formulation of claim 9, wherein the non-ionizable excipient is selected from the group consisting of a sugar or a polysorbate. 13. A method of preparing an aqueous formulation of an antibody, or antigen-binding fragment thereof, at a concentration of at least 50 mg/ml, a non-ionizable excipient, and a buffer, the method comprising: a) providing the antibody, or antigen-binding fragment thereof, in a first solution; b) subjecting the first solution to diafiltration using water as a diafiltration medium until at least a five-fold volume exchange with the water has been achieved to thereby prepare a diafiltered antibody solution; c) concentrating the diafiltered antibody solution and d) adding a non-ionizable excipient and a buffer to the concentrated diafiltered antibody solution, thereby preparing the aqueous formulation of the antibody, or antigen-binding fragment thereof, at a concentration of at least 50 mg/ml, a non-ionizable excipient, and a buffer wherein the antibody, or antigen-binding fragment thereof, has a molecular weight (Mw) greater than about 47 kDa. 14. A method of preparing an aqueous formulation comprising an antibody, or antigen-binding fragment thereof, at a concentration of at least 50 mg/ml, a non-ionizable excipient, and a buffer and water, the method comprising: a) providing the antibody, or antigen-binding fragment thereof, in a first solution; b) subjecting the first solution to diafiltration using water as a diafiltration medium until at least a five-fold volume exchange with the water has been achieved, to prepare a second solution; and c) adding a non-ionizable excipient and a buffer to the second solution, thereby preparing the aqueous formulation, wherein the antibody, or antigen-binding fragment thereof, has a molecular weight (Mw) greater than about 47 kDa. 15. The method of claim 14 or 13, wherein the antibody, antibody, or antigen-binding fragment thereof, is selected from the group consisting of a chimeric antibody, a human antibody, a humanized antibody, and a domain antibody (dAb). 16. The method of claim 14 or 13, wherein the antibody, or antigen-binding fragment thereof, is an anti-tumor necrosis factor alpha (TNF.alpha.) antibody or an anti-interleukin-12 (IL-12) antibody. 17. The method of claim 14 or 13, wherein the antibody, or antigen-binding fragment thereof, is selected from the group consisting of adalimumab, alemtuzumab, Arcitumomab, cetuximab, trastuzumab, imciromab pentetate, capromab pendetide, infliximab, abciximab, rituximab, basiliximab, palivizumab, nofetumomab, omalizumab, daclizumab, ibritumomab tiuxetan, muromonab-CD3, edrecolomab, gemtuzumab ozogamicin, golimumab, certolizumab pegol, eculizumab, ustekinumab, panitumumab, tositumomab and I131 tositumomab, and bevacizumab. 18. The method of claim 14 or 15, wherein the non-ionizable excipient is a sugar or a polysorbate.

Details for Patent 8,883,146

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Centocor Ortho Biotech Products, L.p.	ORTHOCLONE OKT3	muromanab-cd3	Injection	103463	09/14/1992		2027-11-30
Janssen Biotech, Inc.	REOPRO	abciximab	Injection	103575	12/22/1994		2027-11-30
Aytu Bioscience, Inc.	PROSTASCINT	capromab pendetide	Injection	103608	10/28/1996		2027-11-30