Methods of treatment of cellulite

Patent metadata

Field	Value
Publication number	US-9775889-B2
Application number	US-201414243805-A
Country	US
Kind code	B2
Filing date	Apr 2, 2014
Priority date	Mar 6, 2008
Publication date	Oct 3, 2017
Grant date	Oct 3, 2017

Abstract

Methods and combinations are provided for controlling the duration of action, in vivo, of matrix-degrading enzymes. The methods and combinations permit temporary in-vivo activation of matrix-degrading enzymes upon administration to the extra cellular matrix (or “ECM”). Matrix-degrading enzymes having a controlled duration of action can be used to treat ECM-mediated diseases or disorders characterized by increased deposition or accumulation of one or more ECM components.

First claim

The invention claimed is:

1. A method for treating cellulite, comprising administering to a subject a composition comprising a cathepsin L enzyme, wherein:
the composition is administered by subcutaneous administration into the extracellular matrix (ECM) to effect treatment of the cellulite;
the pH of the composition containing the cathepsin L enzyme is 3 to 6.5, whereby the cathepsin L enzyme is active in the composition, and whereby, upon administration into the ECM, the cathepsin L enzyme is active for a limited time after administration to the subject, thereby treating the cellulite; and
the cathepsin L enzyme in the composition:
a) consists of the sequence of amino acid residues whose sequence is set forth in SEQ ID NO:1; or
b) consists of a sequence of amino acid residues that has at least 90% sequence identity with the sequence of amino acid residues set forth in SEQ ID NO:1 and has cathepsin L activity to cleave type I collagen; or
c) is a two-chain form of a) or b), and has cathepsin L activity to cleave type I collagen; or
d) is a catalytically active fragment of the enzymes of any of a)-c) that has cathepsin L activity to cleave type I collagen.

2. The method of claim 1 , wherein the pH of the composition is within a range of about 4.5 to 6.

3. The method of claim 1 , wherein the pH of the composition is within a range of 4 to 6.

4. The method of claim 1 , wherein the pH of the composition is within a range of about 5 to 6.

5. The method of claim 1 , wherein the cathepsin L enzyme is a two-chain form.

6. The method of claim 1 , wherein the cathepsin L enzyme comprises:
a heavy chain having the sequence of amino acids set forth as amino acids 1-175 of SEQ ID NO:1 or a sequence that exhibits at least 90% sequence identity to the sequence of amino acids 1-175; and
a light chain having the sequence of amino acids set forth as amino acids 179-220 of SEQ ID NO:1 or a sequence that exhibits at least 90% sequence identity to the sequence of amino acids 179-220.

7. The method of claim 1 , wherein the cathepsin L enzyme consists of the sequence of amino acid residues set forth in SEQ ID NO:1.

8. The method of claim 1 , wherein the cathepsin L enzyme in the composition is a mature cathepsin L enzyme that is generated from a cathepsin L zymogen by activation cleavage to cleave the prosegment of the Cathepsin L zymogen, thereby producing the mature cathepsin L enzyme.

9. The method of claim 8 , wherein the cleaved prosegment is removed from the composition.

10. The method of claim 8 , wherein the cathepsin L zymogen comprises:
the sequence of amino acids set forth as amino acids 18-333 of SEQ ID NO:62; or
a sequence of amino acids that exhibits at least 90% sequence identity to the sequence of amino acids set forth as amino acids 18-333 of SEQ ID NO:62.

11. The method of claim 8 , wherein the cathepsin L zymogen consists of:
the sequence of amino acids set forth as amino acids 18-333 SEQ ID NO:62; or
a sequence of amino acids that exhibits at least 90% sequence identity to the sequence of amino acids set forth as amino acids 18-333 of SEQ ID NO:62.

12. The method of claim 8 , wherein the cathepsin L zymogen is produced by expression of a nucleic acid encoding the polypeptide set forth in SEQ ID NO:62.

13. The method of claim 12 , wherein the nucleic acid has the sequence of nucleotides set forth in SEQ ID NO:61.

14. The method of claim 1 , wherein the composition comprising the cathepsin L enzyme is prepared by a method comprising:
providing a lyophilized preparation containing the cathepsin L enzyme; and
adding an acidic buffered solution at the acidic pH to the lyophilized preparation, thereby generating an acidic pH composition containing the cathepsin L enzyme.

15. The method of claim 14 , wherein the acidic buffered solution has a pH within a range of 4 to 6.

16. The method of claim 14 , wherein the pH of the acidic buffered solution has a pH within a range of 3.5 to 6.

17. The method of claim 1 , wherein administration is effected by injection.

18. The method of claim 1 , wherein the composition comprises a buffer containing an acid selected from among 2-(N-morpholino)ethanesulfonic acid) (MES), acetic acid, citric acid, succinic acid, lactic acid, maleic acid, glycine-hydrochloric acid, citric phosphate and histidine.

19. The method of claim 1 , wherein:
the composition comprises succinic acid; and
the pH of the composition is within a range of about 4 to 6.

20. The method of claim 1 , wherein the composition is administered to deliver the cathepsin L enzyme in a dosage range amount of, or about, 100 μg to 50 mg.

21. The method of claim 20 , wherein the composition is administered in a volume that is in a range of, or about, 1 mL to 50 mL.

22. The method of claim 1 , wherein:
the composition is administered to deliver the cathepsin L enzyme in a dosage range amount of, or about, 500 μg to 10 mg; and
the composition is administered in a volume that is in a range of, or about, 1 mL to 10 mL.

23. The method of claim 1 , wherein the pH of the composition comprising the cathepsin L is 4 to 6.

Assignees

• Halozyme Inc

Inventors

• Keller Gilbert
• Frost Gregory I

Classifications

• A61P37/02

  Immunomodulators · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P41/00

  Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution · CPC title

• A61P17/02

  for treating wounds, ulcers, burns, scars, keloids, or the like · CPC title