Uses of a dual V region antibody-like protein

Patent metadata

Field	Value
Publication number	US-11008389-B2
Application number	US-201615206045-A
Country	US
Kind code	B2
Filing date	Jul 8, 2016
Priority date	Mar 16, 2011
Publication date	May 18, 2021
Grant date	May 18, 2021

Abstract

Uses of a dual V region antibody-like protein or a fragment of a dual V region antibody-like region.

First claim

The invention claimed is:

1. A stable lyophilized antibody formulation comprising:
100 mg/mL of a bispecific antibody or a bispecific antigen binding fragment thereof, wherein the bispecific antibody or bispecific antibody fragment comprises a light chain variable domain VL hB-B13 , a light chain variable domain VL hBD4-8 , a heavy chain variable domain VH hB-B13 and a heavy chain variable domain VH hBD4-8 , wherein:
VL hB-B13 comprises CDRs comprising the amino acid sequences RASESVDSYGQSYMH (SEQ ID NO:8), LASNLES (SEQ ID NO:9), and QQNAEDSRT (SEQ ID NO:10);
VL hBD4-8 comprises CDRs comprising the amino acid sequences HASQNIDVWLS (SEQ ID NO:14), KASNLHTG (SEQ ID NO:15), and QQAHSYPFT (SEQ ID NO:16),
VH hB-B13 comprises CDRs comprising the amino acid sequences GFSLTDSSIN (SEQ ID NO:11), DGRID (SEQ ID NO:12), and DGYFPYAMDF (SEQ ID NO:13),
VH hBD4-8 comprises CDRs comprising the amino acid sequences GYSFTSYWIH (SEQ ID NO:17), IDPSDGETR (SEQ ID NO:18) and LKEYGNYDSFYFDV (SEQ ID NO:19) or the amino acid sequences GYSFTSYWIH (SEQ ID NO:20), IDASDGETR (SEQ ID NO:21), and LKEYGNYDSFYFDV (SEQ ID NO:22);

10 mM of a buffering system, wherein the buffering system comprises a tromethamine buffer concentration of 3.7 mM and a monobasic sodium phosphate buffer concentration of 6.3 mM;
0.2% (w/v) polysorbate 80;
5% (w/v) sucrose; and
3% (w/v) proline;
wherein the pH of the formulation is about pH 7.

2. The formulation of claim 1 , wherein the bispecific antibody or fragment thereof comprises a heavy chain variable region comprising the amino acid sequences of SEQ ID NOs: 2 and 4, and a light chain variable region comprising the amino acid sequences of SEQ ID NOs: 1 and 3.

3. The formulation of claim 1 , wherein the bispecific antibody or fragment thereof comprises a heavy chain variable region comprising the amino acid sequences of SEQ ID NOs: 2 and 5, and a light chain variable region comprising the amino acid sequences of SEQ ID NOs: 1 and 3.

4. The formulation of claim 1 , wherein:
VL hB-B13 comprises an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO:1,
VL hBD4-8 comprises an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO:3,
VH hB-B13 comprises an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO:2,
VH hBD4-8 comprises an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO:4 or SEQ ID NO:5.

5. The formulation of claim 1 , wherein the bispecific antibody or bispecific antigen fragment comprises light chains comprising the structure N-VL hB-B13 -linker-VL hBD4-8 -CL-C and the heavy chains comprising the structure N-VH hB-B13 -linker-VH hBD4-8 -CH1-CH2-CH3-C.

6. The formulation of claim 5 , wherein the linker comprises the amino acid sequence of SEQ ID NO:6.

7. The formulation of claim 5 , wherein the bispecific antibody or bispecific antibody fragment thereof comprises two light chains and two heavy chains.

8. The formulation of claim 1 , wherein the bispecific antibody or bispecific antibody fragment comprises light chains comprising the structure N-VL hBD4-8 -linker-VL hB-B13 -CL-C and the heavy chains comprising the structure N-VH hBD4-8 -linker-VH hB-B13 -CH1-CH2-CH3-C.

9. The formulation of claim 8 , wherein the linker comprises the amino acid sequence of SEQ ID NO:6.

10. The formulation of claim 8 , wherein the bispecific antibody or bispecific antibody fragment thereof comprises two light chains and two heavy chains.

11. The formulation of claim 1 , wherein the formulation is for administration to an individual in need thereof subcutaneously at a dose of 10 mg to 300 mg.

Assignees

• Sanofi Sa

Inventors

• Bender Florent C
• Li Danxi
• Minnich Anne
• Naadimuthu Amirtha
• Rao Ercole
• Swanson Brian N
• Tang Lei
• Yu Haixin
• Boussif Otmane
• Carayon Sophie

Classifications

• C07K2317/64

  comprising a combination of variable region and constant region components · CPC title

• C07K2317/75

  Agonist effect on antigen · CPC title

• C07K2317/73

  Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation · CPC title

• C07K2317/76

  Antagonist effect on antigen, e.g. neutralization or inhibition of binding · CPC title

• C07K2317/565

  Complementarity determining region [CDR] · CPC title