IP Library › Granted Patent US 12,655,225
Granted Patent B2
US 12,655,225 · App. 17/112,768 · Granted Jun 16, 2026

Formulations of anti-CD38 antibodies for subcutaneous administration

Inventors: Sylvain Huille (Paris, FR); Thomas Ballet (Paris, FR); Kiran Bangari (Bridgewater, NJ); Ravi Chari (Bridgewater, NJ); Bernardo Perez-Ramirez (Bridgewater, NJ); Filipe Vasco (Paris, FR)
Assignee: SANOFI-AVENTIS U.S. LLC
C07K16/2896C07K2317/565C07K2317/94
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Quick Facts
Patent No.
US 12,655,225
App. No.
17/112,768
Granted
Jun 16, 2026
Kind
B2
Abstract

Provided are formulations of anti-CD38 antibodies suitable for subcutaneous administration to a subject in need thereof. The formulations include a high concentration of antibody, a viscosity lowering agent, a stabilizing agent, a buffering agent and a surfactant. In certain embodiments, the viscosity of the solution is at most 25 mPa·s, and the pH of the solution is 5.9 to 7.0. In certain embodiments, the anti-CD38 antibody is isatuximab. The formulations will find use in treating CD38 + hematological malignancies, including multiple myeloma, as well as autoimmune and inflammatory diseases, in humans.

Claims (76)

1 . An antibody formulation suitable for subcutaneous administration comprising:

(i) 125-155 mg/ml isatuximab, and

(ii) excipients consisting of:

(a) histidine,

(b) 90-125 mM arginine (Arg),

(c) sucrose,

(c) 0.4% (w/v) Poloxamer 188,

wherein the antibody formulation has a pH of 5.9-6.3 and a viscosity of at most 25 mPa·s at 20° C.

2 . The antibody formulation of claim 1 , wherein the Arg is at a concentration of 110 mM Arg.

3 . The antibody formulation of claim 1 , wherein the histidine is at a concentration of 9 mM histidine.

4 . The antibody formulation of claim 1 , wherein the antibody formulation comprises 140 mg/ml isatuximab.

5 . The antibody formulation of claim 1 , wherein the sucrose is at a concentration of 2% (w/v) sucrose.

6 . The antibody formulation of claim 1 , wherein the pH is 6.2-6.3.

7 . The antibody formulation of claim 1 , wherein the formulation has a viscosity of at most 14 mPa·s at 20° C.

8 . The antibody formulation of claim 1 , wherein the subcutaneous administration comprises a large-volume subcutaneous infusion.

9 . The antibody formulation of claim 8 , wherein the large-volume subcutaneous infusion comprises an infusion volume of 5 mL to 30 mL.

10 . The antibody formulation of claim 9 , wherein the large-volume subcutaneous infusion comprises an infusion volume of 10 mL to 15 mL.

11 . The antibody formulation of claim 10 , wherein the large-volume subcutaneous infusion comprises an infusion volume of 10 mL to 12 mL.

12 . An antibody formulation suitable for subcutaneous administration, wherein the antibody formulation comprises:

(i) 125-155 mg/ml isatuximab, and

(ii) excipients consisting of:

(a) histidine,

(b) 90-125 mM arginine (Arg),

(c) sucrose, and

(d) Poloxamer 188,

wherein the antibody formulation has a pH of 5.9-6.3 and

wherein the subcutaneous administration comprises a large-volume subcutaneous infusion.

13 . The antibody formulation of claim 12 , wherein the large-volume subcutaneous infusion comprises an infusion volume of 5 mL to 30 mL.

14 . The antibody formulation of claim 13 , wherein the large-volume subcutaneous infusion comprises an infusion volume of 10 mL to 15 mL.

15 . The antibody formulation of claim 14 , wherein the large-volume subcutaneous infusion comprises an infusion volume of 10 mL to 12 mL.

16 . A packaged pharmaceutical product comprising a sterile container or a device, the sterile container or device comprising a therapeutically effective amount of a formulation suitable for subcutaneous administration comprising:

(i) 125-155 mg/ml isatuximab, and

(ii) excipients consisting of:

(a) histidine,

(b) 90-125 mM arginine (Arg),

(c) sucrose, and

(d) 0.4% (w/v) Poloxamer 188,

wherein the formulation has a pH of 5.9-6.3 and

wherein the subcutaneous administration comprises a large-volume subcutaneous infusion.

17 . The packaged pharmaceutical product of claim 16 , wherein the large-volume subcutaneous infusion comprises an infusion volume of 10 mL to 12 mL.

18 . The packaged pharmaceutical product of claim 16 , wherein the formulation has a viscosity of at most 25 mPa's at 20° C.

19 . The packaged pharmaceutical product of claim 16 , wherein the device is selected from a syringe, a syringe driver, a pre-filled syringe, and an infusion pump.

20 . An antibody formulation suitable for large volume subcutaneous administration, comprising:

(i) 125-155 mg/ml isatuximab, and

(ii) excipients consisting of:

(a) 9 mM histidine,

(b) 90-125 mM arginine (Arg),

(c) 2% (w/v) sucrose, and

(d) 0.4% (w/v) Poloxamer 188,

wherein the antibody formulation does not include hyaluronidase; and

wherein the large volume subcutaneous administration comprises an infusion volume of 10 mL to 12 mL.

21 . An antibody formulation suitable for subcutaneous administration, comprising:

(i) 125-155 mg/ml isatuximab, and

(ii) excipients consisting of:

(a) histidine,

(b) 90-125 mM arginine (Arg),

(c) sucrose, and

(d) Poloxamer 188,

wherein the antibody formulation has a pH of 5.9-6.3, wherein the subcutaneous administration comprises a large-volume subcutaneous infusion, and wherein the antibody formulation does not include hyaluronidase.

22 . The antibody formulation of claim 21 , wherein the formulation has a pH of 5.9-6.3 and a viscosity of at most 25 mPa·s at 20° C.

23 . The antibody formulation of claim 21 , wherein the antibody formulation has a viscosity of at most 14 mPa·s at 20° C.

24 . The antibody formulation of claim 21 , wherein the antibody formulation comprises 140 mg/ml isatuximab.

25 . The antibody formulation of claim 21 , wherein the large-volume subcutaneous infusion comprises an infusion volume of 5 mL to 30 mL.

26 . The antibody formulation of claim 21 , wherein the large-volume subcutaneous infusion comprises an infusion volume of 10 mL to 12 mL.

27 . An antibody formulation suitable for subcutaneous administration, wherein the antibody formulation comprises:

(i) 125-155 mg/ml isatuximab; and

(ii) excipients consisting of:

(a) 9 mM histidine,

(b) 90-125 mM arginine,

(c) 2% (w/v) sucrose, and

(d) 0.4% (w/v) Poloxamer 188, and

wherein the antibody formulation has a pH of 5.9-6.3 and a viscosity of at most 25 mPa·s at 20° C.

28 . The antibody formulation of claim 27 , wherein the Arg is at a concentration of 110 mM Arg.

29 . The antibody formulation of claim 27 , wherein the antibody formulation comprises 140 mg/ml isatuximab.

30 . The antibody formulation of claim 29 , wherein the pH is 6.2-6.3.

31 . The antibody formulation of claim 29 , wherein the antibody formulation has a viscosity of at most 14 mPa·s at 20° C.

Assignments (4)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 11, 2022
From: SANOFI-AVENTIS RECHERCHE & DEVELOPPEMENT
To: SANOFI-AVENTIS U.S. LLC
Reel/Frame 059953/0329 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 10, 2022
From: BALLET, THOMAS; HUILLE, SYLVAIN; FILIPE, VASCO
To: SANOFI-AVENTIS RECHERCHE & DEVELOPPEMENT
Reel/Frame 059880/0695 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 10, 2022
From: BANGARI, KIRAN; CHARI, RAVI; PEREZ-RAMIREZ, BERNARDO
To: GENZYME CORPORATION
Reel/Frame 059880/0805 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 10, 2022
From: GENZYME CORPORATION
To: SANOFI-AVENTIS U.S. LLC
Reel/Frame 059926/0354 →
Continuity (2)
Provisional Application 62944082 · Dec 5, 2019
Related Publication 20210188996A1 · Jun 24, 2021
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