Anti-cd38 antibodies and formulations
AssigneeSanofi
InventorsMarielle CHIRON BLONDEL, Cendrine LEMOINE, Angela VIRONE-ODDOS, Béatrice CAMERON, Jacques DUMAS, Alain FOURNIER, Jonathan KINGSBURY, Brian MURRAY, Nathan OSTBERG, Sanket PATKE, Zichuan ZHANG
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Abstract
Provided herein are antibodies that specifically bind human CD38, formulations and unit dosage forms comprising the antibodies, methods of preparing the antibodies and methods of using the antibodies.
Claims26
An antibody that specifically binds human CD38, wherein the antibody comprises
- a) a heavy chain (HC) having an amino acid sequence of SEQ ID NO:
- 2 and a light chain (LC) having an amino acid sequence of SEQ ID NO:
- 7, or
- b) a heavy chain (HC) having an amino acid sequence of SEQ ID NO:
- 3 and a light chain (LC) having an amino acid sequence of SEQ ID NO:
- 7, or
- c) a heavy chain (HC) having an amino acid sequence of SEQ ID NO:
- 4 and a light chain (LC) having an amino acid sequence of SEQ ID NO:
- 7, or
- d) a heavy chain (HC) having an amino acid sequence of SEQ ID NO:
- 5 and a light chain (LC) having an amino acid sequence of SEQ ID NO:
- 8, or
- e) a heavy chain (HC) having an amino acid sequence of SEQ ID NO:
- 5 and a light chain (LC) having an amino acid sequence of SEQ ID NO:
- 9, or
- f) a heavy chain (HC) having an amino acid sequence of SEQ ID NO:
- 6 and a light chain (LC) having an amino acid sequence of SEQ ID NO:
- 8, or
- g) a heavy chain (HC) having an amino acid sequence of SEQ ID NO:
- 6 and a light chain (LC) having an amino acid sequence of SEQ ID NO:
- 9.
A pharmaceutical composition comprising a formulated antibody, wherein the formulated antibody comprises an antibody, sucrose, L-histidine, and polysorbate 80 (PS80), wherein the antibody specifically binds human CD38 and is present at a concentration of 50 mg/mL, the sucrose is present at a concentration of 8% (w/v), the L-histidine is present at a concentration of 10 mM, and the PS80 is present at a concentration of 0.05% (v/v), wherein the formulation has a pH of 6.2, and wherein the antibody comprises
- a) a heavy chain (HC) having an amino acid sequence of SEQ ID NO:
- 2 and a light chain (LC) having an amino acid sequence of SEQ ID NO:
- 7, or
- b) a heavy chain (HC) having an amino acid sequence of SEQ ID NO:
- 3 and a light chain (LC) having an amino acid sequence of SEQ ID NO:
- 7, or
- c) a heavy chain (HC) having an amino acid sequence of SEQ ID NO:
- 4 and a light chain (LC) having an amino acid sequence of SEQ ID NO:
- 7, or
- d) a heavy chain (HC) having an amino acid sequence of SEQ ID NO:
- 5 and a light chain (LC) having an amino acid sequence of SEQ ID NO:
- 8, or
- e) a heavy chain (HC) having an amino acid sequence of SEQ ID NO:
- 5 and a light chain (LC) having an amino acid sequence of SEQ ID NO:
- 9, or
- f) a heavy chain (HC) having an amino acid sequence of SEQ ID NO:
- 6 and a light chain (LC) having an amino acid sequence of SEQ ID NO:
- 8, or
- g) a heavy chain (HC) having an amino acid sequence of SEQ ID NO:
- 6 and a light chain (LC) having an amino acid sequence of SEQ ID NO:
- 9.
A unit dosage form of a formulated antibody that specifically binds human CD38, wherein the formulated antibody comprises 215 mg of the antibody, 6.21 mg L-histidine, 344 mg sucrose, and 2.15 mg polysorbate 80, wherein the formulated antibody is lyophilized, and wherein the antibody comprises
- a) a heavy chain (HC) having an amino acid sequence of SEQ ID NO:
- 2 and a light chain (LC) having an amino acid sequence of SEQ ID NO:
- 7, or
- b) a heavy chain (HC) having an amino acid sequence of SEQ ID NO:
- 3 and a light chain (LC) having an amino acid sequence of SEQ ID NO:
- 7, or
- c) a heavy chain (HC) having an amino acid sequence of SEQ ID NO:
- 4 and a light chain (LC) having an amino acid sequence of SEQ ID NO:
- 7, or
- d) a heavy chain (HC) having an amino acid sequence of SEQ ID NO:
- 5 and a light chain (LC) having an amino acid sequence of SEQ ID NO:
- 8, or
- e) a heavy chain (HC) having an amino acid sequence of SEQ ID NO:
- 5 and a light chain (LC) having an amino acid sequence of SEQ ID NO:
- 9, or
- f) a heavy chain (HC) having an amino acid sequence of SEQ ID NO:
- 6 and a light chain (LC) having an amino acid sequence of SEQ ID NO:
- 8, or
- g) a heavy chain (HC) having an amino acid sequence of SEQ ID NO:
- 6 and a light chain (LC) having an amino acid sequence of SEQ ID NO:
- 9.
A method for preparing a pharmaceutical composition comprising an antibody that specifically binds human CD38, wherein the antibody comprises
- a) a heavy chain (HC) having an amino acid sequence of SEQ ID NO:
- 2 and a light chain (LC) having an amino acid sequence of SEQ ID NO:
- 7, or
- b) a heavy chain (HC) having an amino acid sequence of SEQ ID NO:
- 3 and a light chain (LC) having an amino acid sequence of SEQ ID NO:
- 7, or
- c) a heavy chain (HC) having an amino acid sequence of SEQ ID NO:
- 4 and a light chain (LC) having an amino acid sequence of SEQ ID NO:
- 7, or
- d) a heavy chain (HC) having an amino acid sequence of SEQ ID NO:
- 5 and a light chain (LC) having an amino acid sequence of SEQ ID NO:
- 8, or
- e) a heavy chain (HC) having an amino acid sequence of SEQ ID NO:
- 5 and a light chain (LC) having an amino acid sequence of SEQ ID NO:
- 9, or
- f) a heavy chain (HC) having an amino acid sequence of SEQ ID NO:
- 6 and a light chain (LC) having an amino acid sequence of SEQ ID NO:
- 8, or
- g) a heavy chain (HC) having an amino acid sequence of SEQ ID NO:
- 6 and a light chain (LC) having an amino acid sequence of SEQ ID NO:
- 9,
- the method comprising the steps of:
- i) expressing the antibody in a cell culture;
- ii) subjecting the antibody to at least one purification step selected from the group consisting of chromatography and ultrafiltration to produce a purified antibody solution;
- and
- iii) adjusting the purified antibody solution to produce a formulated antibody comprising
- the purified antibody at a concentration of 50 mg/mL,
- sucrose at a concentration of 8% w/v,
- L-histidine at a concentration of 10 mM, and
- polysorbate 80 at a concentration of 0.05% v/v,
- wherein the formulated antibody has a pH of 6.2;
- and
- iv) lyophilizing the formulated antibody,
- thereby preparing the pharmaceutical composition.
A method for preparing a reconstituted formulated antibody, comprising
- a) providing a lyophilized antibody formulation comprising sucrose, L-histidine, polysorbate 80, and an antibody that specifically binds human CD38;
- and
- b) reconstituting the lyophilized antibody formulation in a diluent, wherein the reconstituted antibody formulation comprises
- the antibody at a concentration of 50 mg/mL,
- sucrose at a concentration of 8% w/v,
- L-Histidine at a concentration of 10 mM, and
- polysorbate 80 at a concentration of 0.05% v/v,
- wherein the reconstituted antibody formulation has a pH of 6.2;
- wherein the antibody comprises
- i) a heavy chain (HC) having an amino acid sequence of SEQ ID NO:
- 2 and a light chain (LC) having an amino acid sequence of SEQ ID NO:
- 7, or
- ii) a heavy chain (HC) having an amino acid sequence of SEQ ID NO:
- 3 and a light chain (LC) having an amino acid sequence of SEQ ID NO:
- 7, or
- iii) a heavy chain (HC) having an amino acid sequence of SEQ ID NO:
- 4 and a light chain (LC) having an amino acid sequence of SEQ ID NO:
- 7, or
- iv) a heavy chain (HC) having an amino acid sequence of SEQ ID NO:
- 5 and a light chain (LC) having an amino acid sequence of SEQ ID NO:
- 8, or
- v) a heavy chain (HC) having an amino acid sequence of SEQ ID NO:
- 5 and a light chain (LC) having an amino acid sequence of SEQ ID NO:
- 9, or
- vi) a heavy chain (HC) having an amino acid sequence of SEQ ID NO:
- 6 and a light chain (LC) having an amino acid sequence of SEQ ID NO:
- 8, or
- vii) a heavy chain (HC) having an amino acid sequence of SEQ ID NO:
- 6 and a light chain (LC) having an amino acid sequence of SEQ ID NO:
- 9.
A method of treating a patient in need thereof, comprising administering to the patient one or more doses of an antibody that specifically binds human CD38, wherein the patient has a disease that comprises CD38-expressing cells, wherein the antibody comprises
- a) a heavy chain (HC) having an amino acid sequence of SEQ ID NO:
- 2 and a light chain (LC) having an amino acid sequence of SEQ ID NO:
- 7, or
- b) a heavy chain (HC) having an amino acid sequence of SEQ ID NO:
- 3 and a light chain (LC) having an amino acid sequence of SEQ ID NO:
- 7, or
- c) a heavy chain (HC) having an amino acid sequence of SEQ ID NO:
- 4 and a light chain (LC) having an amino acid sequence of SEQ ID NO:
- 7, or
- d) a heavy chain (HC) having an amino acid sequence of SEQ ID NO:
- 5 and a light chain (LC) having an amino acid sequence of SEQ ID NO:
- 8, or
- e) a heavy chain (HC) having an amino acid sequence of SEQ ID NO:
- 5 and a light chain (LC) having an amino acid sequence of SEQ ID NO:
- 9, or
- f) a heavy chain (HC) having an amino acid sequence of SEQ ID NO:
- 6 and a light chain (LC) having an amino acid sequence of SEQ ID NO:
- 8, or
- g) a heavy chain (HC) having an amino acid sequence of SEQ ID NO:
- 6 and a light chain (LC) having an amino acid sequence of SEQ ID NO:
- 9.
(canceled)
Dependencies are inferred from the claim text.