Methods for treating systemic sclerosis

Patent metadata

Field	Value
Publication number	US-11827671-B2
Application number	US-202016881863-A
Country	US
Kind code	B2
Filing date	May 22, 2020
Priority date	May 24, 2019
Publication date	Nov 28, 2023
Grant date	Nov 28, 2023

Abstract

The invention provides methods for treating Systemic Sclerosis by administering a dual-V region bispecific antibody that specifically binds IL-4 and IL-13.

First claim

What is claimed is:

1. A method for treating systemic sclerosis (SSc) in a human subject with SSc, the methods comprising administering about 200 mg of a dual-V-region bispecific antibody or antigen-binding fragment that specifically binds IL-4 and IL-13 subcutaneously to the subject, wherein a portion of human subjects treated have an improved modified Rodnan Skin Score (mRSS) of at least 20% at 24 weeks after initial administration of the bispecific antibody or antigen-binding fragment compared to baseline.

2. The method of claim 1 , wherein 200 mg of the bispecific antibody is administered to the subject about once per week or about every 5 to 9 days.

3. The method of claim 1 , wherein the treatment is given for at least about 24 weeks.

4. The method of claim 1 , wherein the bispecific antibody is in a pharmaceutical formulation.

5. The method of claim 4 , wherein the pharmaceutical formulation comprises about 100 mg/ml bispecific antibody, about 6.3 mM monobasic sodium phosphate, about 37 mM Tris, about 5% (w/v) sucrose, about 3% (w/v) proline, and about 0.2% (w/v) polysorbate 80, wherein the pH of the formulation is about 7.0.

6. The method of claim 5 , wherein the formulation is reconstituted from a lyophilized formulation.

7. The method of claim 1 , wherein the bispecific antibody is administered in combination with another agent.

8. The method of claim 7 , wherein the another agent is administered before, simultaneous with, or after administration of the bispecific antibody.

9. The method of claim 1 , wherein the systemic sclerosis is diffuse cutaneous systemic sclerosis.

10. The method of claim 1 , wherein the bispecific antibody or bispecific antibody fragment thereof comprises a light chain polypeptide comprising a light chain variable domain VL hB-B13 and a light chain variable domain VL hBD4-8 , and a heavy chain polypeptide comprising a heavy chain variable domain VH hB-B13 and a heavy chain variable domain VH hBD4-8 , wherein:
VL hB-B13 comprises the three CDRs comprising the amino acid sequences

(SEQ ID NO: 8)

RASESVDSYGQSYMH,

(SEQ ID NO: 9)

LASNLES,

and

(SEQ ID NO: 10)

QQNAEDSRT;

VL hBD4-8 comprises the three CDRs comprising the amino acid sequences

(SEQ ID NO: 14)

HASQNIDVWLS,

(SEQ ID NO: 15)

KASNLHTG,

and

(SEQ ID NO: 16)

QQAHSYPFT,

VH hB-B13 comprises the three CDRs comprising the amino acid sequences

(SEQ ID NO: 11)

GFSLTDSSIN,

(SEQ ID NO: 12)

DGRID,

and

(SEQ ID NO: 13)

DGYFPYAMDF,

VH hBD4-8 comprises the three CDRs comprising the amino acid sequences

(SEQ ID NO: 17)

GYSFTSYWIH,

(SEQ ID NO: 18)

IDPSDGETR

and

(SEQ ID NO: 19)

LKEYGNYDSFYFDV.

11. The method of claim 10 , 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, and
VH hBD4-8 comprises an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO:4.

12. The method of claim 10 , wherein:
VL hB-B13 comprises the amino acid sequence of SEQ ID NO:1,
VL hBD4-8 comprises the amino acid sequence of SEQ ID NO:3,
VH hB-B13 comprises the amino acid sequence of SEQ ID NO:2, and
VH hBD4-8 comprises the amino acid sequence of SEQ ID NO:4.

13. The method of claim 10 , wherein the light chain polypeptide comprises the structure N-VL hB-B13 -linker-VL hBD4-8 -CL-C and the heavy chain polypeptide comprises the structure N-VH hB-B13 -linker-V hBD4-8 -CH1-C.

14. The method of claim 10 , wherein the light chains comprise the structure N-VL hB-B13 -linker-VL hBD4-8 -CL-C and the heavy chains comprise the structure N-VH hB-B13 -linker-VH hBD4-8 -CH1-CH2-CH3-C.

15. The method of claim 14 , wherein the linker comprises the amino acid sequence of SEQ ID NO:6.

16. The method of claim 10 , wherein the bispecific antibody or bispecific antibody fragment thereof comprises two identical light chain polypeptides and two identical heavy chain polypeptides.

17. The method of claim 10 , wherein the light chain polypeptide comprises an amino acid sequence having at least about 90% identity to the amino acid sequence of SEQ ID NO:22 and the heavy chain polypeptide comprises an amino acid sequence having at least about 90% identit

Assignees

• Sanofi Sa

Inventors

• Soubrane Christina
• Esperet Corinne
• Marrache Frederic
• Wung Peter

Classifications

• A61K47/02

  Inorganic compounds · CPC title

• A61K9/19

  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 title

• A61K47/18

  Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids · CPC title

• A61K47/183

  Amino acids, e.g. glycine, EDTA or aspartame · CPC title

• A61K47/26

  Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin · CPC title