Anti-TNF antibody formulations

• US 9,085,619 B2
• Filed: 10/03/2014
• Issued: 07/21/2015
• Est. Priority Date: 11/30/2007
• Status: Active Grant

• Current Assignee: AbbVie Biotechnology Ltd. (Puerto Rico) (Abbvie Incorporated)
• Original Assignee: AbbVie Biotechnology Ltd. (Puerto Rico) (Abbvie Incorporated)
• Inventors: Fraunhofer, Wolfgang, Bartl, Annika, Krause, Hans-Juergen, Tschoepe, Markus
• Primary Examiner(s): Landsman, Robert
• Assistant Examiner(s): Hissong, Bruce D
• Application Number:
  US14/506,576
• Publication Number:
  US 20150023977A1
• Time in Patent Office: 291 Days
• US Class Current: 1/1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 38/21 Interferons [IFN]
• CPC Class Codes: A61K 38/385 Serum albumin
• CPC Class Codes: A61K 38/46 Hydrolases (3)
• CPC Class Codes: A61K 38/4893 Botulinum neurotoxin (3.4.24.69)
• CPC Class Codes: A61K 38/50 acting on carbon-nitrogen bonds, other than peptide bonds (3.5), e.g. asparaginase
• CPC Class Codes: A61K 39/395 Antibodies agglutinins A61K38/36 ; as drug carriers A61K47/50; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61K 39/39591 Stabilisation, fragmentation
• 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: A61K 9/08 Solutions composition of solutions A61K47/00
• CPC Class Codes: A61K 9/19 lyophilised , i.e. freeze-dried, solutions or dispersions lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00
• CPC Class Codes: C07K 1/34 by filtration, ultrafiltration or reverse osmosis
• CPC Class Codes: C07K 16/241 Tumor Necrosis Factors
• CPC Class Codes: C07K 16/244 Interleukins [IL]
• CPC Class Codes: C07K 2317/21 from primates, e.g. man
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C07K 2317/94 Stability, e.g. half-life, pH, temperature or enzyme-resistance

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.

Claims

1. An aqueous pharmaceutical formulation consisting essentially of:

(a) an anti-tumor necrosis factor alpha antibody comprising 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, wherein the concentration of the antibody is 50 to 200 mg/ml; and

(b) water.

2. The formulation of claim 1, wherein the antibody comprises a LCVR comprising the amino acid sequence set forth in SEQ ID NO:

1, and a HCVR comprising the amino acid sequence set forth in SEQ ID NO;

2.

3. The formulation of claim 2, wherein the antibody is adalimumab.

4. The formulation of claim 1, wherein the pH of the formulation is from 4 to 8.

5. The formulation of claim 3, wherein the pH of the formulation is from 4 to 8.

6. An aqueous pharmaceutical formulation comprising:

(a) an anti-tumor necrosis factor alpha antibody comprising 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, wherein the concentration of the antibody is 50 to 200 mg/ml; and

(b) water;

wherein the formulation does not comprise a tonicity modifier.

7. The formulation of claim 6, wherein the antibody comprises a LCVR comprising the amino acid sequence set forth in SEQ ID NO:

1, and a HCVR comprising the amino acid sequence set forth in SEQ ID NO;

2.

8. The formulation of claim 7, wherein the antibody is adalimumab.

9. The formulation of claim 6, wherein the pH of the formulation is from 4 to 8.

10. The formulation of claim 6, wherein the pH of the formulation is from 4 to 6.

11. The formulation of claim 6, wherein the pH of the formulation is from 5 to 6.

12. The formulation of claim 8, wherein the pH of the formulation is from 4 to 8.

13. The formulation of claim 8, wherein the pH of the formulation is from 4 to 6.

14. The formulation of claim 8, wherein the pH of the formulation is from 5 to 6.

15. The formulation of claim 8, wherein the pH of the formulation is 5.2.

16. An aqueous pharmaceutical formulation comprising:

(a) an anti-tumor necrosis factor alpha antibody comprising 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, wherein the concentration of the antibody is 50 to 200 mg/ml; and

(b) water;

wherein the formulation does not comprise a buffering system.

17. The formulation of claim 16, wherein the antibody comprises a LCVR comprising the amino acid sequence set forth in SEQ ID NO:

1, and a HCVR comprising the amino acid sequence set forth in SEQ ID NO;

2.

18. The formulation of claim 17, wherein the antibody is adalimumab.

19. The formulation of claim 16, wherein the formulation further comprises a non-ionizable excipient.

20. The formulation of claim 16, wherein the formulation further comprises a polyol.

21. The formulation of claim 20, wherein the polyol is selected from the group consisting of mannitol, sorbitol, and sucrose.

22. The formulation of claim 16, wherein the formulation further comprises a surfactant.

23. The formulation of claim 22, wherein the surfactant is selected from the group consisting of polysorbate 80 and polysorbate 20.

24. The formulation of claim 16, wherein the pH of the formulation is from 4 to 8.

25. The formulation of claim 16, wherein the pH of the formulation is from 4 to 6.

26. The formulation of claim 16, wherein the pH of the formulation is from 5 to 6.

27. The formulation of claim 18, wherein the pH of the formulation is from 4 to 8.

28. The formulation of claim 18, wherein the pH of the formulation is from 4 to 6.

29. The formulation of claim 18, wherein the pH of the formulation is from 5 to 6.

30. The formulation of claim 18, wherein the pH of the formulation is 5.2.