CD38 ANTIBODY-BASED FORMULATIONS FOR SUBCUTANEOUS ADMINISTRATION

Claims

1. A formulation suitable for subcutaneous administration comprising at least 100 mg / ml of an anti-CD38 antibody, wherein the anti-CD38 antibody comprises a heavy chain variable region (VH) comprising three complementarity determining regions (CDRs) CDR-H1, CDR-H2 and CDR-H3 comprising the amino acid sequences of SEQ ID NO: 1-3, respectively, and a light chain variable region (VL) comprising three CDRs: CDR-L1, CDR-L2 and CDR-L3, comprising the amino acid sequences of SEQ ID NO: 4-6, respectively, the composition contains a viscosity reducer, a stabilizer, a buffering agent and a surfactant, The pH of the composition is 5.9-7.0 and the viscosity is no more than 25 mPa⋅s at 20°C.

2. A formulation suitable for subcutaneous administration comprising at least 100 mg / ml of an anti-CD38 antibody, wherein the anti-CD38 antibody comprises a heavy chain variable region (VH) comprising three complementarity determining regions (CDRs) CDR-H1, CDR-H2 and CDR-H3 comprising the amino acid sequences of SEQ ID NO: 1-3, respectively, and a light chain variable region (VL) comprising three CDRs: CDR-L1, CDR-L2 and CDR-L3, comprising the amino acid sequences of SEQ ID NO: 4-6, respectively, the composition contains a viscosity reducer, a stabilizer, a buffering agent and a surfactant, The pH of the composition is 5.9-7.0 and the viscosity is no more than 25 mPa⋅s at 20°C, and where subcutaneous administration is the subcutaneous administration of a large volume and is carried out by infusion or injection.

3. A formulation suitable for subcutaneous administration comprising at least 100 mg / ml of an anti-CD38 antibody, wherein the anti-CD38 antibody comprises a heavy chain variable region (VH) comprising three complementarity determining regions (CDRs) CDR-H1, CDR-H2 and CDR-H3 comprising the amino acid sequences of SEQ ID NO: 1-3, respectively, and a light chain variable region (VL) comprising three CDRs: CDR-L1, CDR-L2 and CDR-L3, comprising the amino acid sequences of SEQ ID NO: 4-6, respectively, the composition contains a viscosity reducing agent, stabilizer, buffering agent and surfactant, The pH of the composition is 5.9-7.0 and the viscosity is no more than 25 mPa⋅s at 20°C, and wherein the subcutaneous administration is by infusion in a volume of from 5 ml to 30 ml; and wherein the composition does not contain hyaluronidase.

4. The composition according to any one of paragraphs 1-3, wherein the viscosity reducing agent comprises: (i) 90-150 mM arginine (Arg); (ii) 90-125 mM Arg; (iii) 110 mM Arg; (iv) 90-150 mM Lys-Ac; or (v) 125 mM Lys-Ac.

5. The composition according to any one of paragraphs 1-4, wherein the surfactant contains: (i) Poloxamer 188; (ii) 0.4% (w / v) Poloxamer 188; (iii) Polysorbate 80; or (iv) 0.04% (w / v) Polysorbate 80.

6. A composition according to any one of paragraphs 1-5, wherein the surfactant comprises: (i) Polysorbate 80; or (ii) 0.04% (w / v) Polysorbate 80.

7. The composition according to any one of paragraphs 1-6, wherein the buffering agent comprises: (i) histidine; or (ii) 9 mM histidine.

8. The composition according to any one of paragraphs 1-7, wherein the stabilizer contains: (i) sucrose; or (ii) 2% (w / v) sucrose.

9. A composition according to any one of paragraphs 1-8, in which the composition: (i) has a pH of 5.9-6.5; (ii) has a pH of 6.2-6.3; (iii) has a viscosity of not more than 14 mPa⋅s at 20°C; (iv) contains Lys-Ac, sucrose and Polysorbate 80; or (v) contains Lys-Ac, sucrose, Polysorbate 80 and has a pH of 6.2 and a viscosity of not more than 14 mPa⋅s at 20°C.

10. The composition according to any one of paragraphs 1-9, wherein the antibody comprises: (i) the heavy chain variable domain (VH) of the anti-CD38 antibody comprises the amino acid sequences set forth in SEQ ID NO: 7, and the light chain variable domain (VL) of the anti-CD38 antibody comprises the amino acid sequences set forth in SEQ ID NO: 8; (ii) the heavy chain of the anti-CD38 antibody comprises the amino acid sequences set forth in SEQ ID NO: 9 and the light chain of the anti-CD38 antibody comprises the amino acid sequences set forth in SEQ ID NO: 10; or (iii) the CD38 antibody is isatuximab.

11. The composition according to any one of paragraphs 1-10, where the composition: (i) contains 125-155 mg / ml of antibody to CD38; (ii) contains 140 mg / ml antibody to CD38; (iii) is a large volume for subcutaneous infusion, comprising 10 to 12 ml; or (iv) is a device containing a therapeutically effective amount of the composition; or (vi) does not contain hyaluronidase.

12. Use of a composition according to any of paragraphs 1-11 for the treatment of a disease or condition characterized by: (i) the presence or activity of CD38+ cells; (ii) the presence or activity of CD38+ cells is a CD38+ hematological malignancy; (iii) the presence or activity of CD38+ cells is indicative of an autoimmune or inflammatory disease or condition; (iv) the presence or activity of CD38+ cells indicates a CD38+ hematological malignancy and the hematological malignancy is multiple myeloma; or (v) the presence or activity of CD38+ cells indicates a hematological malignancy, and the hematological malignancy is relapsed / refractory multiple myeloma.