Dry powder formulations of thymic stromal lymphopoietin (TSLP)-binding antibodies and methods of use thereof

Patent metadata

Field	Value
Publication number	US-11904053-B2
Application number	US-202017081821-A
Country	US
Kind code	B2
Filing date	Oct 27, 2020
Priority date	Oct 28, 2019
Publication date	Feb 20, 2024
Grant date	Feb 20, 2024

Abstract

The present technology relates generally to dry powder formulations of antibodies specific for thymic stromal lymphopoietin (TSLP), as well as methods of treating asthma, using the dry powder formulations, suitably via pulmonary delivery.

First claim

What is claimed is:

1. A dry powder formulation comprising a plurality of microparticles, the microparticles comprising:
a. about 8% to about 11% leucine by weight;
b. about 2% to about 4% trileucine by weight; and
c. an antigen binding fragment of an anti-thymic stromal lymphopoietin (TSLP) antibody comprising:
a heavy chain variable domain comprising:
i. a heavy chain CDR1 sequence consisting of the amino acid sequence set forth in SEQ ID NO:1;
ii. a heavy chain CDR2 sequence consisting of the amino acid sequence set forth in SEQ ID NO:2; and
iii. a heavy chain CDR3 sequence consisting of the amino acid sequence set forth in SEQ ID NO:3, and

a light chain variable domain comprising:
i. a light chain CDR1 sequence consisting of the amino acid sequence set forth in SEQ ID NO:5;
ii. a light chain CDR2 sequence consisting of the amino acid sequence set forth in SEQ ID NO:6, and
iii. a light chain CDR3 sequence consisting of the amino acid sequence set forth in SEQ ID NO:7.

2. The dry powder formulation of claim 1 , wherein the dry powder formulation has a compressed bulk density of about 0.4-1.0 g/cm 3 .

3. The dry powder formulation of claim 1 , further comprising a glass stabilization agent.

4. The dry powder formulation of claim 3 , wherein:
a. the glass stabilization agent is an amorphous saccharide or a buffer; or
b. the glass stabilization agent comprises an amorphous saccharide and a buffer.

5. The dry powder formulation of claim 4 , wherein the amorphous saccharide is selected from the group consisting of trehalose, sucrose, raffinose, inulin, dextran, mannitol, and cyclodextrin.

6. The dry powder formulation of claim 4 , wherein the buffer is selected from the group consisting of a citrate buffer, a phosphate buffer, a histidine buffer, a glycine buffer, an acetate buffer and a tartrate buffer.

7. The dry powder formulation of claim 4 , wherein the amorphous saccharide is trehalose.

8. The dry powder formulation of claim 1 , wherein the formulation comprises about 10.5% leucine by weight and about 2% trileucine by weight.

9. The dry powder formulation of claim 1 , wherein the formulation further comprises a surfactant, and wherein the surfactant is selected from polysorbate-20 (PS-20), polysorbate-40 (PS-40), polysorbate-60 (PS-60), polysorbate-80 (PS-80) and poloxamer-188.

10. The dry powder formulation of claim 9 , wherein the surfactant is PS-80, and wherein PS-80 is present at a concentration in the range of from about 0.27% by weight to about 2.7% by weight, or from about 0.67% by weight to about 1.33% by weight.

11. The dry powder formulation of claim 10 , wherein the PS-80 is present at a concentration of about 1.1% by weight.

12. A dry powder formulation comprising a plurality of microparticles, the microparticles comprising:
a. about 10.5% leucine by weight;
b. about 2% trileucine by weight;
c. from about 1% to about 40% by weight of an antigen binding fragment of an anti-thymic stromal lymphopoietin (TSLP) antibody comprising:
a heavy chain variable domain comprising:
i. a heavy chain CDR1 sequence consisting of the amino acid sequence set forth in SEQ ID NO:1;
ii. a heavy chain CDR2 sequence consisting of the amino acid sequence set forth in SEQ ID NO:2; and
iii. a heavy chain CDR3 sequence consisting of the amino acid sequence set forth in SEQ ID NO:3, and

a light chain variable domain comprising:
i. a light chain CDR1 sequence consisting of the amino acid sequence set forth in SEQ ID NO:5;
ii. a light chain CDR2 sequence consisting of the amino acid sequence set forth in SEQ ID NO:6, and
iii. a light chain CDR3 sequence consisting of the amino acid sequence set forth in SEQ ID NO:7;

d. about 1.1% by weight polysorbate-80;
e. buffer; and
f. trehalose in an amount by weight to make up to 100%.

13. The dry powder formulation of claim 1 , wherein the
a. the heavy chain variable domain comprises SEQ ID NO:4; and
b. the light chain variable domain comprises SEQ ID NO:8.

14. The dry powder formulation of claim 12 , wherein:
a. the heavy chain variable domain comprises SEQ ID NO:4; and
b. the light chain variable domain comprises SEQ ID NO:8.

15. The dry powder formulation of claim 14 , wherein the heavy chain has the sequence set forth in SEQ ID NO:28 and the light chain has the sequence set forth in SEQ ID NO:29.

16. The dry powder formulation of claim 1 , wherein the antigen binding fragment is selected from Fab, Fab′, F(ab′)2, scFv, minibody, or diabody.

17. The dry powder formulation of claim 16 , wherein the antigen binding fragment is a Fab.

18. The dry powder formulation of claim 17 , wherein the Fab is human or humanized.

19. The dry powder formulation of claim 1 , wherein the anti-TSLP antibody from which the antigen binding fragment is derived is an IgG1.

Assignees

• Medimmune Ltd

Inventors

• Huntington Catherine Eugenie Chaillan
• Hoe Susan
• Manikwar Prakash
• Kolbeck Roland Wilhelm
• Cohen Emma Suzanne
• Lechuga-Ballesteros David
• Hansen Kellisa Beth
• D'Sa Dexter Joseph
• Ghazvini Saba

Classifications

• A61K9/1623 Primary

  Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules · CPC title

• A61K9/0075 Primary

  for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles · CPC title

• A61K9/1652

  Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin (homeopathic globules A61K9/1623) · CPC title

• C07K16/244 Primary

  Interleukins [IL] · CPC title

• C07K2317/24

  containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered · CPC title