ANTI-CD19 ANTIBODY FORMULATIONS

• US 20190322742A1
• Filed: 06/27/2017
• Published: 10/24/2019
• Est. Priority Date: 06/27/2016
• Status: Active Grant

• Current Assignee: Incyte Corporation
• Original Assignee: Morphosys Ag
• Inventors: Garidel, Patrick, Langer, Andreas, Hessling, Martin, Weinfurtner, Daniel, Brocks, Bodo
• Granted Patent: US 11,352,423 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 31/715 Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
• CPC Class Codes: A61K 39/39591 Stabilisation, fragmentation
• CPC Class Codes: A61K 47/36 Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
• CPC Class Codes: A61K 47/549 Sugars, nucleosides, nucleotides or nucleic acids
• 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: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07K 16/2803 against the immunoglobulin superfamily

Abstract

The present disclosure describes a pharmaceutical formulation of an anti-CD19 antibody.

Claims

1. :

A stable lyophilized pharmaceutical formulation, the formulation comprising an anti-CD19 antibody in a concentration of 20 mg/ml to 125 mg/ml, a buffer, polysorbate in a concentration of 0.005% (w/v) to 0.06% (w/v), and pH of 6.0, wherein the formulation further comprises

a) trehalose in a concentration of 180 mM to 240 mM or

b) mannitol in a concentration of 180 mM to 240 mM and sucrose in a concentration of 10 mM to 50 mM,

and wherein said anti-CD19 antibody comprises a heavy chain constant domain of the sequence ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYS LSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPDVFLFPP KPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVV HQDWLNGKEYKCKVSNKALPAPEEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFY PSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYT QKSLSLSPGK (SEQ ID NO;

     8) and a light chain constant domain of the sequence RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKD STYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC. (SEQ ID NO;

     9).

2. :

The formulation of claim 1, wherein said anti-CD19 antibody in the formulation is 40 mg/ml.

3. :

The formulation of claim 1, wherein said buffer is citrate buffer or phosphate buffer.

4. :

The formulation of claim 3, wherein said citrate buffer or phosphate buffer are in a concentration of between 20 and 50 mM.

5. :

The formulation of claim 4, wherein said citrate buffer or phosphate buffer are in a concentration of 25 mM.

6. :

The formulation of claim 1, wherein said trehalose in the formulation is 200 mM.

7. :

The formulation of claim 1, wherein said mannitol in the formulation is 219 mM and said sucrose in the formulation is 29 mM.

8. :

The formulation of claim 1 wherein said polysorbate in the formulation is polysorbate 20.

9. :

The formulation of claim 1, wherein said polysorbate in the formulation is 0.02%.

10. :

The formulation of claim 1, wherein said anti-CD19 antibody is an IgG1, an IgG2, an IgG3 or an IgG4 antibody.

11. :

The formulation of claim 1, wherein the formulation is stable at 2-8°

C. for at least 6 months, at least 12 months, at least 18 months, at least 24 months or at least 36 months.

12. :

The formulation of claim 1, wherein said anti-CD19 antibody is in an amount of 40 mg/mL, said citrate buffer in a concentration of 25 mM, said trehalose in a concentration of 200 mM, said polysorbate in a concentration of 0.02% (w/v) and said formulation has a pH of 6.0.

13. :

The formulation of claim 1, wherein said anti-CD19 antibody is in an amount of 40 mg/mL, said citrate buffer in a concentration of 25 mM, said mannitol in a concentration of 219 mM and said sucrose in a concentration of 29 mM, said polysorbate in a concentration of 0.02% (w/v) and said formulation has a pH of 6.0.

14. :

An article of manufacture comprising a container holding the stable lyophilized pharmaceutical formulation of claim 1.

15. :

A method of treating a disease or disorder in a subject comprising administering an effective amount of the formulation of claim 1 to the subject, wherein the disease or disorder is cancer.