IP Library Granted Patent US 10,487,115
Granted Patent B2
US 10,487,115 · App. 16/074,690 · Granted Nov 26, 2019

Proteinaceous compounds and uses therefor

Inventors: Sudha Rao (Deakin, AU); Peter Milburn (O'Connor, AU)
Assignee: UNIVERSITY OF CANBERRA
C07K7/08A61K38/17A61K38/43A61P35/00A61K38/00
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Quick Facts
Patent No.
US 10,487,115
App. No.
16/074,690
Granted
Nov 26, 2019
Kind
B2
Abstract

Disclosed are proteinaceous molecules and their use in conditions associated with PKC-θ overexpression, such as cancer. More particularly, the present invention discloses proteinaceous molecules and their use in altering at least one of (i) formation; (ii) proliferation; (iii) maintenance; (iv) epithelial to mesenchymal cell transition; or (v) mesenchymal to epithelial cell transition of a PKC-θ overexpressing cell.

Claims (72)

1. A method of altering at least one of (i) formation; (ii) proliferation; (iii) maintenance; (iv) epithelial to mesenchymal cell transition; or (v) mesenchymal to epithelial cell transition of a PKC-θ overexpressing cell, comprising contacting said PKC-θ overexpressing cell with an isolated or purified proteinaceous molecule represented by Formula I:

Z 1 X 1 X 2 X 3 X 4 IDX 5 PPX 6 X 7 X 8 X 9 X 10 X 11 Z 2   (I)

wherein:

“Z 1 ” and “Z 2 ” are independently absent or are independently selected from at least one of a proteinaceous moiety comprising from about 1 to about 50 amino acid residues, and a protecting moiety;

“X 1 ” is absent or is selected from basic amino acid residues including R, K and modified forms thereof;

“X 2 ” and “X 3 ” are independently selected from basic amino acid residues including R, K and modified forms thereof;

“X 4 ” is selected from charged amino acid residues including R, K, D, E and modified forms thereof;

“X 5 ” is absent or is W or modified forms thereof;

“X 6 ” is selected from aromatic or basic amino acid residues including F, Y, W, R, K and modified forms thereof;

“X 7 ” is selected from basic amino acid residues including R, K and modified forms thereof;

“X 8 ” is absent or is P or modified forms thereof;

“X 9 ” is selected from basic amino acid residues including R, K and modified forms thereof;

“X 10 ” is selected from hydrophobic residues including V, L, I, M and modified forms thereof and P and modified forms thereof;

“X 11 ” is selected from basic amino acid residues including R, K and modified forms thereof.

2. The method according to claim 1 , wherein the PKC-θ overexpressing cell is a cancer stem cell or a non-cancer stem cell tumor cell.

3. A method of treating or preventing a cancer in a subject, wherein the cancer comprises at least one PKC-θ overexpressing cell, comprising administering to the subject an isolated or purified proteinaceous molecule represented by Formula I as defined in claim 1 .

4. The method according to claim 1 , wherein “X 1 ” is absent or is R.

5. The method according to claim 1 , wherein “X 2 ” is R.

6. The method according to claim 1 , wherein “X 3 ” is K.

7. The method according to claim 1 , wherein “X 4 ” is E or R.

8. The method according to claim 1 , wherein “X 5 ” is absent or is W.

9. The method according to claim 1 , wherein “X 6 ” is F or R.

10. The method according to claim 1 , wherein “X 7 ” is R.

11. The method according to claim 1 , wherein “X 9 ” is K.

12. The method according to claim 1 , wherein “X 10 ” is V or P.

13. The method according to claim 1 , wherein “X 11 ” is K.

14. The method according to claim 1 , wherein “Z 1 ” is a proteinaceous molecule represented by Formula II:

X 12 X 13 X 14 X 15 X 16   (II)

wherein:

“X 12 ” is absent or is a protecting moiety;

“X 13 ” is absent or is selected from P and basic amino acid residues including R, K and modified forms thereof;

“X 14 ” is absent or is selected from P and basic amino acid residues including R, K and modified forms thereof;

“X 15 ” is absent or is selected from P and basic amino acid residues including R, K and modified forms thereof;

“X 16 ” is absent or is selected from P and basic amino acid residues including R, K and modified forms thereof.

15. The method according to claim 1 , wherein “Z 1 ” and “Z 2 ” are absent.

16. The method according to claim 1 , wherein the proteinaceous molecule of Formula I comprises an amino acid sequence represented by SEQ ID NO: 1 or 2:

[SEQ ID NO: 1]

RKEIDPPFRPKVK

or

[SEQ ID NO: 2]

RRKRIDWPPRRKPK.

17. The method according to claim 1 , wherein the proteinaceous molecule of Formula I further comprises at least one membrane permeating moiety, wherein the membrane permeating moiety is a myristoyl group.

18. An isolated or purified proteinaceous molecule represented by Formula I:

Z 1 X 1 X 2 X 3 X 4 IDX 5 PPX 6 X 7 X 8 X 9 X 10 X 11 Z 2   (I)

wherein:

“Z 1 ” and “Z 2 ” are independently absent or are independently selected from at least one of a proteinaceous moiety comprising from about 1 to about 50 amino acid residues, and a protecting moiety;

“X 1 ” is absent or is selected from basic amino acid residues including R, K and modified forms thereof;

“X 2 ” and “X 3 ” are independently selected from basic amino acid residues including R, K and modified forms thereof;

“X 4 ” is selected from charged amino acid residues including R, K, D, E and modified forms thereof;

“X 5 ” is absent or is W or modified forms thereof;

“X 6 ” is selected from aromatic or basic amino acid residues including F, Y, W, R, K and modified forms thereof;

“X 7 ” is selected from basic amino acid residues including R, K and modified forms thereof;

“X 8 ” is absent or is P or modified forms thereof;

“X 9 ” is selected from basic amino acid residues including R, K and modified forms thereof;

“X 10 ” is selected from hydrophobic residues including V, L, I, M and modified forms thereof and P or modified forms thereof;

“X 11 ” is selected from basic amino acid residues including R, K and modified forms thereof;

wherein the proteinaceous molecule is other than a proteinaceous molecule consisting of the amino acid sequence of SEQ ID NO: 1:

[SEQ ID NO: 1]

RKEIDPPFRPKVK.

19. The proteinaceous molecule according to claim 18 , wherein “X 1 ” is absent or is R.

20. The proteinaceous molecule according to claim 18 , wherein “X 2 ” is R.

21. The proteinaceous molecule according to claim 18 , wherein “X 3 ” is K.

22. The proteinaceous molecule according to claim 18 , wherein “X 4 ” is E or R.

23. The proteinaceous molecule according to claim 18 , wherein “X 5 ” is absent or is W.

24. The proteinaceous molecule according to claim 18 , wherein “X 6 ” is F or R.

25. The proteinaceous molecule according to claim 18 , wherein “X 7 ” is R.

26. The proteinaceous molecule according to claim 18 , wherein “X 9 ” is K.

27. The proteinaceous molecule according to claim 18 , wherein “X 10 ” is V or P.

28. The proteinaceous molecule according to claim 18 , wherein “X 11 ” is K.

29. The proteinaceous molecule according to claim 18 , wherein the proteinaceous molecule comprises the amino acid sequence of SEQ ID NO: 2:

[SEQ ID NO: 2]

RRKRIDWPPRRKPK.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 22, 2019
From: UNIVERSITY OF CANBERRA
To: EPIAXIS THERAPEUTICS PTY LTD
Reel/Frame 051085/0376 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 10, 2019
From: RAO, SUDHA; MILBURN, PETER
To: UNIVERSITY OF CANBERRA
Reel/Frame 050700/0413 →
Priority Claims (1)
AU 2016900314 · Feb 1, 2016 · national
Continuity (1)
Related Publication 20190040103A1 · Feb 7, 2019