IP Library › Granted Patent US 7,795,223
Granted Patent B2
US 7,795,223 · App. 11/597,320 · Granted Sep 14, 2010

Treatment of inflammatory airway disease

Assignee: Novozymes Biopharma Au Ltd.
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Quick Facts
Patent No.
US 7,795,223
App. No.
11/597,320
Granted
Sep 14, 2010
Kind
B2
Abstract

This invention relates to methods of treatment of inflammatory airway disease, and in particular to methods of treatment of asthma and chronic obstructive pulmonary disease. The invention is applicable to both allergic (atopic) and non-allergic (intrinsic) asthma. In one form the method comprises the step of administering an effective amount of a compound which has the ability to inhibit one or more functions of the T cell receptor (TCR) to a subject in need of such treatment, which is preferably a peptide whose sequence is derived from an invariant region of (a) the TCR α transmembrane domain; (b) the TCR β transmembrane domain; (c) the TCR α intracellular domain; or (d) the CD3-γ, -δ, -ε, η or ξ chain.

Claims (241)

1. A method of treatment of inflammatory airway or lung disease, comprising the step of administering an effective amount of a peptide which has the ability to inhibit one or more functions of the T cell receptor (TCR) to a subject in need of such treatment, in which the peptide has a sequence selected from the grow consisting of:

(SEQ. ID. NO. 1)

NH 2 -Gly-Leu-Arg-Ile-Leu-Leu-Leu-Lys-Val-OH;

(SEQ. ID. NO. 2)

NH 2 -Leu-Lys-Ile-Leu-Leu-Leu-Arg-Val-OH;

(SEQ. ID. NO. 3)

NH 2 -Gly-Phe-Arg-Ile-Leu-Leu-Leu-Lys-Val-OH;

(SEQ. ID. NO. 4)

NH 2 -Val-Phe-Arg-Ile-Leu-Leu-Leu-Lys-Val-OH;

(SEQ. ID. NO. 5)

NH 2 -Phe-Lys-Ile-Leu-Leu-Leu-Arg-Val-OH;

(SEQ. ID. NO. 6)

NH 2 -Ala-Arg-Leu-Pro-Val-Leu-Lys-Leu-Val-OH;

(SEQ. ID. NO. 7)

NH 2 -Arg-Val-Met-Ala-Pro-Arg-Ala-Leu-Leu-OH;

(SEQ. ID. NO. 8)

NH 2 -Val-Lys-Leu-Phe-Pro-Val-Lys-Leu-Phe-Pro-OH;

(SEQ. ID. NO. 9)

NH 2 -Leu-Arg-Ile-Leu-Leu-Leu-Ile-Lys-Val-OH;

(SEQ. ID. NO. 10)

NH 2 -Leu-Arg-Leu-Leu-Leu-Lys-Val-OH.

(SEQ. ID. NO. 11)

NH 2 -Met-Gly-Leu-Arg-Ile-Leu-Leu-Leu-OH;

(SEQ. ID. NO. 12)

NH 2 -Leu-Asp-Ile-Leu-Leu-Leu-Glu-Val-OH;

(SEQ. ID. NO. 13)

NH 2 -Ile-Leu-Leu-Leu-Lys-Val-Ala-Gly-Phe-OH;

(SEQ. ID. NO. 14)

NH 2 -Ile-Leu-Leu-Leu-Lys-Val-Ala-Gly-OH;

(SEQ. ID. NO. 15)

NH 2 -Leu-Arg-Ile-Leu-Leu-Leu-Gly-Val-OH;

(SEQ. ID. NO. 16)

NH 2 -Leu-Gly-Ile-Leu-Leu-Leu-Lys-Val-OH;

(SEQ. ID. NO. 17)

NH 2 -Ile-Leu-Leu-Gly-Lys-Ala-Thr-Leu-Tyr-OH;

(SEQ. ID. NO. 18)

NH 2 -Leu-Leu-Met-Thr-Leu-Arg-Leu-Trp-Ser-Ser-OH;

(SEQ. ID. NO. 19)

NH 2 -Ile-Ile-Val-Thr-Asp-Val-Ile-Ala-Thr-Leu-OH;

(SEQ. ID. NO. 20)

NH 2 -Ile-Val-Ile-Val-Asp-Ile-Cys-Ile-Thr-OH;

(SEQ. ID. NO. 21)

NH 2 -Phe-Leu-Phe-Ala-Glu-Ile-Val-Ser-Ile-OH;

(SEQ. ID. NO. 22)

NH 2 -Tyr-Gly-Arg-Ala-Asp-Cys-Gly-Ile-Thr-Ser-OH;

(SEQ. ID. NO. 23)

NH 2 -Trp-Gly-Arg-Ala-Asp-Cys-Gly-Ile-Thr-Ser-OH;

(SEQ. ID. NO. 24)

NH 2 -Tyr-Gly-Arg-Ala-Asp-Cys-Ile-Thr-Ser-OH;

and

(SEQ. ID. NO. 25)

NH 2 -Ser-Ser-Asp-Val-Pro-Cys-Asp-Ala-Thr-Leu-Thr-

OH;

wherein the C-terminus of said peptide is conjugated to a lipid moiety selected from: N-palmitoyl-S-[2,3-bis(palmitoyloxy)propyl]cysteine (Pam3Cys), or an analogue thereof in which only two acyl substituents are present.

2. A method according to claim 1 , in which the peptide is NH 2 -Leu-Arg-Ile-Leu-Leu-Leu-Gly-Val-OH (SEQ. ID. NO. 15), NH 2 -Leu-Leu-Met-Thr-Leu-Arg-Leu-Trp-Ser-Ser-OH (SEQ. ID. NO. 18) or NH 2 -Ile-Val-Ile-Val-Asp-Ile-Cys-Ile-Thr-OH (SEQ. ID. NO. 20).

3. A method according to claim 1 , in which the peptide is NH 2 -Ile-Val-Ile-Val-Asp-Ile-Cys-Ile-Thr-OH (SEQ. ID. NO. 20).

4. A method according to claim 1 , in which the peptide comprises a cysteine residue, and has the ability to destabilize the interchain disulphide bond between the TCR α and TCR β chains.

5. A method of treatment of inflammatory airway or lung disease, comprising the step of administering an effective amount of a peptide which has the ability to inhibit one or more functions of the T cell receptor (TCR) to a subject, in which the peptide has a sequence selected from the group consisting of:

(SEQ. ID. NO. 1)

NH 2 -Gly-Leu-Arg-Ile-Leu-Leu-Leu-Lys-Val-OH;

(SEQ. ID. NO. 2)

NH 2 -Leu-Lys-Ile-Leu-Leu-Leu-Arg-Val-OH;

(SEQ. ID. NO. 3)

NH 2 -Gly-Phe-Arg-Ile-Leu-Leu-Leu-Lys-Val-OH;

(SEQ. ID. NO. 4)

NH 2 -Val-Phe-Arg-Ile-Leu-Leu-Leu-Lys-Val-OH;

(SEQ. ID. NO. 5)

NH 2 -Phe-Lys-Ile-Leu-Leu-Leu-Arg-Val-OH;

(SEQ. ID. NO. 6)

NH 2 -Ala-Arg-Leu-Pro-Val-Leu-Lys-Leu-Val-OH;

(SEQ. ID. NO. 7)

NH 2 -Arg-Val-Met-Ala-Pro-Arg-Ala-Leu-Leu-OH;

(SEQ. ID. NO. 8)

NH 2 -Val-Lys-Leu-Phe-Pro-Val-Lys-Leu-Phe-Pro-OH;

(SEQ. ID. NO. 9)

NH 2 -Leu-Arg-Ile-Leu-Leu-Leu-Ile-Lys-Val-OH;

(SEQ. ID. NO. 10)

NH 2 -Leu-Arg-Leu-Leu-Leu-Lys-Val-OH;

(SEQ. ID. NO. 11)

NH 2 -Met-Gly-Leu-Arg-Ile-Leu-Leu-Leu-OH;

(SEQ. ID. NO. 12)

NH 2 -Leu-Asp-Ile-Leu-Leu-Leu-Glu-Val-OH;

(SEQ. ID. NO. 13)

NH 2 -Ile-Leu-Leu-Leu-Lys-Val-Ala-Gly-Phe-OH;

(SEQ. ID. NO. 14)

NH 2 -Ile-Leu-Leu-Leu-Lys-Val-Ala-Gly-OH;

(SEQ. ID. NO. 15)

NH 2 -Leu-Arg-Ile-Leu-Leu-Leu-Gly-Val-OH;

(SEQ. ID. NO. 16)

NH 2 -Leu-Gly-Ile-Leu-Leu-Leu-Lys-Val-OH;

(SEQ. ID. NO. 17)

NH 2 -Ile-Leu-Leu-Gly-Lys-Ala-Thr-Leu-Tyr-OH;

(SEQ. ID. NO. 18)

NH 2 -Leu-Leu-Met-Thr-Leu-Arg-Leu-Trp-Ser-Ser-OH;

(SEQ. ID. NO. 19)

NH 2 -Ile-Ile-Val-Thr-Asp-Val-Ile-Ala-Thr-Leu-OH;

(SEQ. ID. NO. 20)

NH 2 -Ile-Val-Ile-Val-Asp-Ile-Cys-Ile-Thr-OH;

(SEQ. ID. NO. 21)

NH 2 -Phe-Leu-Phe-Ala-Glu-Ile-Val-Ser-Ile-OH;

(SEQ. ID. NO. 22)

NH 2 -Tyr-Gly-Arg-Ala-Asp-Cys-Gly-Ile-Thr-Ser-OH;

(SEQ. ID. NO. 23)

NH 2 -Trp-Gly-Arg-Ala-Asp-Cys-Gly-Ile-Thr-Ser-OH;

(SEQ. ID. NO. 24)

NH 2 -Tyr-Gly-Arg-Ala-Asp-Cys-Ile-Thr-Ser-OH;

and

(SEQ. ID. NO. 25)

NH 2 -Ser-Ser-Asp-Val-Pro-Cys-Asp-Ala-Thr-Leu-Thr-OH;

wherein the C-terminus of said peptide is conjugated to a lipid moiety selected from: N-palmitoyl-S-[2,3-bis(palmitoyloxy)propyl]cysteine (Pam3Cys), or an analogue thereof in which only two acyl substituents are present.

6. A method according to claim 1 , in which the inflammatory airway or lung disease is asthma.

7. A method according to claim 1 , in which the inflammatory airway or lung disease is chronic obstructive pulmonary disease.

8. A method according to claim 1 , in which the peptide is administered intravenously, subcutaneously, intratracheally, intrabronchially, intranasally or via inhalation.

9. A method according to claim 8 , in which the peptide is administered via inhalation.

10. A method according to claim 9 , in which the peptide is administered utilising an aerosol, nebuliser or dry powder inhalation device.

11. A composition comprising a peptide selected from the group consisting of:

(SEQ. ID. NO. 1)

NH 2 -Gly-Leu-Arg-Ile-Leu-Leu-Leu-Lys-Val-OH;

(SEQ. ID. NO. 2)

NH 2 -Leu-Lys-Ile-Leu-Leu-Leu-Arg-Val-OH;

(SEQ. ID. NO. 3)

NH 2 -Gly-Phe-Arg-Ile-Leu-Leu-Leu-Lys-Val-OH;

(SEQ. ID. NO. 4)

NH 2 -Val-Phe-Arg-Ile-Leu-Leu-Leu-Lys-Val-OH;

(SEQ. ID. NO. 5)

NH 2 -Phe-Lys-Ile-Leu-Leu-Leu-Arg-Val-OH;

(SEQ. ID. NO. 6)

NH 2 -Ala-Arg-Leu-Pro-Val-Leu-Lys-Leu-Val-OH;

(SEQ. ID. NO. 7)

NH 2 -Arg-Val-Met-Ala-Pro-Arg-Ala-Leu-Leu-OH;

(SEQ. ID. NO. 8)

NH 2 -Val-Lys-Leu-Phe-Pro-Val-Lys-Leu-Phe-Pro-OH;

(SEQ. ID. NO. 9)

NH 2 -Leu-Arg-Ile-Leu-Leu-Leu-Ile-Lys-Val-OH;

(SEQ. ID. NO. 10)

NH 2 -Leu-Arg-Leu-Leu-Leu-Lys-Val-OH;

(SEQ. ID. NO. 11)

NH 2 -Met-Gly-Leu-Arg-Ile-Leu-Leu-Leu-OH;

(SEQ. ID. NO. 12)

NH 2 -Leu-Asp-Ile-Leu-Leu-Leu-Glu-Val-OH;

(SEQ. ID. NO. 13)

NH 2 -Ile-Leu-Leu-Leu-Lys-Val-Ala-Gly-Phe-OH;

(SEQ. ID. NO. 14)

NH 2 -Ile-Leu-Leu-Leu-Lys-Val-Ala-Gly-OH;

(SEQ. ID. NO. 15)

NH 2 -Leu-Arg-Ile-Leu-Leu-Leu-Gly-Val-OH;

(SEQ. ID. NO. 16)

NH 2 -Leu-Gly-Ile-Leu-Leu-Leu-Lys-Val-OH;

(SEQ. ID. NO. 17)

NH 2 -Ile-Leu-Leu-Gly-Lys-Ala-Thr-Leu-Tyr-OH;

(SEQ. ID. NO. 18)

NH 2 -Leu-Leu-Met-Thr-Leu-Arg-Leu-Trp-Ser-Ser-OH;

(SEQ. ID. NO. 19)

NH 2 -Ile-Ile-Val-Thr-Asp-Val-Ile-Ala-Thr-Leu-OH;

(SEQ. ID. NO. 20)

NH 2 -Ile-Val-Ile-Val-Asp-Ile-Cys-Ile-Thr-OH;

(SEQ. ID. NO. 21)

NH 2 -Phe-Leu-Phe-Ala-Glu-Ile-Val-Ser-Ile-OH;

(SEQ. ID. NO. 22)

NH 2 -Tyr-Gly-Arg-Ala-Asp-Cys-Gly-Ile-Thr-Ser-OH;

(SEQ. ID. NO. 23)

NH 2 -Trp-Gly-Arg-Ala-Asp-Cys-Gly-Ile-Thr-Ser-OH;

(SEQ. ID. NO. 24)

NH 2 -Tyr-Gly-Arg-Ala-Asp-Cys-Ile-Thr-Ser-OH;

and

(SEQ. ID. NO. 25)

NH 2 -Ser-Ser-Asp-Val-Pro-Cys-Asp-Ala-Thr-Leu-Thr-OH;

wherein the C-terminus of said peptide is conjugated to a lipid moiety selected from: N-palmitoyl-S-[2,3-bis(palmitoyloxy)propyl]cysteine (Pam3Cys), or an analogue thereof in which only two acyl substituents are present.

12. A composition according to claim 11 , which is in ready-to-administer form in a sealed vial, container or cartridge.

13. A composition according to claim 11 , in which the composition is sterile.

14. A composition according to claim 11 , in which the composition comprises a stabilizer and/or a bulking agent.

15. A composition according to claim 12 , in which the composition is suitable for delivery by inhalation, and in which the sealed vial, container or cartridge is an inhalation device adapted to deliver the composition to a patient via inhalation.

16. A composition according to claim 15 , in which the inhalation device comprises an aerosol, nebuliser or dry powder delivery mechanism.

17. A composition according to claim 15 , in which the inhalation device comprises an aerosol.

18. A composition according to claim 15 , in which the inhalation device delivers the composition in dry powder form.

19. A composition according to claim 15 , in which the inhalation device comprises a nebuliser.

20. A composition according to claim 11 , in which the composition does not require reconstitution before use.

21. An article of manufacture, comprising a peptide selected from the group consisting of:

(SEQ. ID. NO. 1)

NH 2 -Gly-Leu-Arg-Ile-Leu-Leu-Leu-Lys-Val-OH;

(SEQ. ID. NO. 2)

NH 2 -Leu-Lys-Ile-Leu-Leu-Leu-Arg-Val-OH;

(SEQ. ID. NO. 3)

NH 2 -Gly-Phe-Arg-Ile-Leu-Leu-Leu-Lys-Val-OH;

(SEQ. ID. NO. 4)

NH 2 -Val-Phe-Arg-Ile-Leu-Leu-Leu-Lys-Val-OH;

(SEQ. ID. NO. 5)

NH 2 -Phe-Lys-Ile-Leu-Leu-Leu-Arg-Val-OH;

(SEQ. ID. NO. 6)

NH 2 -Ala-Arg-Leu-Pro-Val-Leu-Lys-Leu-Val-OH;

(SEQ. ID. NO. 7)

NH 2 -Arg-Val-Met-Ala-Pro-Arg-Ala-Leu-Leu-OH;

(SEQ. ID. NO. 8)

NH 2 -Val-Lys-Leu-Phe-Pro-Val-Lys-Leu-Phe-Pro-OH;

(SEQ. ID. NO. 9)

NH 2 -Leu-Arg-Ile-Leu-Leu-Leu-Ile-Lys-Val-OH;

(SEQ. ID. NO. 10)

NH 2 -Leu-Arg-Leu-Leu-Leu-Lys-Val-OH;

(SEQ. ID. NO. 11)

NH 2 -Met-Gly-Leu-Arg-Ile-Leu-Leu-Leu-OH;

(SEQ. ID. NO. 12)

NH 2 -Leu-Asp-Ile-Leu-Leu-Leu-Glu-Val-OH;

(SEQ. ID. NO. 13)

NH 2 -Ile-Leu-Leu-Leu-Lys-Val-Ala-Gly-Phe-OH;

(SEQ. ID. NO. 14)

NH 2 -Ile-Leu-Leu-Leu-Lys-Val-Ala-Gly-OH;

(SEQ. ID. NO. 15)

NH 2 -Leu-Arg-Ile-Leu-Leu-Leu-Gly-Val-OH;

(SEQ. ID. NO. 16)

NH 2 -Leu-Gly-Ile-Leu-Leu-Leu-Lys-Val-OH;

(SEQ. ID. NO. 17)

NH 2 -Ile-Leu-Leu-Gly-Lys-Ala-Thr-Leu-Tyr-OH;

(SEQ. ID. NO. 18)

NH 2 -Leu-Leu-Met-Thr-Leu-Arg-Leu-Trp-Ser-Ser-OH;

(SEQ. ID. NO. 19)

NH 2 -Ile-Ile-Val-Thr-Asp-Val-Ile-Ala-Thr-Leu-OH;

(SEQ. ID. NO. 20)

NH 2 -Ile-Val-Ile-Val-Asp-Ile-Cys-Ile-Thr-OH;

(SEQ. ID. NO. 21)

NH 2 -Phe-Leu-Phe-Ala-Glu-Ile-Val-Ser-Ile-OH;

(SEQ. ID. NO. 22)

NH 2 -Tyr-Gly-Arg-Ala-Asp-Cys-Gly-Ile-Thr-Ser-OH;

(SEQ. ID. NO. 23)

NH 2 -Trp-Gly-Arg-Ala-Asp-Cys-Gly-Ile-Thr-Ser-OH;

(SEQ. ID. NO. 24)

NH 2 -Tyr-Gly-Arg-Ala-Asp-Cys-Ile-Thr-Ser-OH;

and

(SEQ. ID. NO. 25)

NH 2 -Ser-Ser-Asp-Val-Pro-Cys-Asp-Ala-Thr-Leu-Thr-OH;

wherein the C-terminus of said peptide is conjugated to a lipid moiety selected from: N-palmitoyl-S-[2,3-bis(palmitoyloxy)propyl]cysteine (Pam3Cys), or an analogue thereof in which only two acyl substituents are present together with a pharmaceutically acceptable carrier, in a dosage form suitable for administration by a patient.

22. An article of manufacture according to claim 21 , in which the dosage form is labeled with, or accompanied by, instructions for treating or preventing inflammatory airway or lung disease in a human.

23. An article of manufacture according to claim 21 , which is a sealed vial, container or cartridge containing a ready-to-administer composition.

24. An article of manufacture according to claim 21 , in which the article of manufacture is a sterile composition.

25. An article of manufacture according to claim 21 , in which the article of manufacture is a composition comprising a stabilizer and/or a bulking agent.

26. An article of manufacture according to claim 23 , in which the sealed vial, container or cartridge is an inhalation device adapted to deliver the composition to the patient via inhalation.

27. An article of manufacture according to claim 26 , in which the inhalation device comprises an aerosol.

28. An article of manufacture according to claim 26 , in which the inhalation device delivers the composition in dry powder form.

29. An article of manufacture according to claim 26 , in which the inhalation device comprises a nebuliser.

30. An article of manufacture according to claim 21 , in which the article of manufacture is a composition that does not require reconstitution before use.

31. An article of manufacture according to claim 21 , further comprising said peptide in a dosage form suitable for administration to a patient with asthma.

32. An article of manufacture according to claim 21 , further comprising said peptide in a dosage form suitable for administration to a patient suffering from chronic obstructive pulmonary disease.

Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 2, 2010
From: NOVOZYMES BIOPHARMA AU LIMITED
To: NOVOZYMES BIOPHARMA DK A/S
Reel/Frame 025436/0584 →
CHANGE OF NAME Recorded Jun 17, 2010
From: GROPEP LIMITED
To: NOVOZYMES GROPEP LIMITED
Reel/Frame 024550/0302 →
CHANGE OF NAME Recorded Jun 17, 2010
From: NOVOZYMES GROPEP LIMITED
To: NOVOZYMES BIOPHARMA AU LIMITED
Reel/Frame 024550/0515 →
Continuity (2)
Provisional Application 6057459200 · May 27, 2004
Related Publication 20080200394A1 · Aug 21, 2008