US2011118193A1PendingUtilityA1

Treatment of liquid cancers

Individually held — no corporate assignee on recordPriority: May 9, 2000Filed: Dec 23, 2009Published: May 19, 2011

Est. expiryMay 9, 2020(expired)· nominal 20-yr term from priority

Inventors:Christopher R. Tudan Ahmed Merzouk Lakhdar Arab Geeta Saxena Connie Eaves Joanne Cashman Ian Clark-Lewis Mary A. Richter Michael Clark-Lewis Hassan Salari

A61K 38/10A61P 35/02C12N 5/0647C12N 2501/21A61K 48/00C07K 14/522C07K 14/4703A61P 35/00A61K 38/1709A61P 43/00

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References

Claims

Abstract

A use of a composition comprising an SDF-1 peptide having the sequence KGVSLSYR is taught. The composition can be used in the manufacture of a medicament for the treatment of a blood cancer in a mammal by administering the medicament in a therapeutically effective amount.

Claims

exact text as granted — not AI-modified

1 . A composition comprising a peptide having KGVSLSYR (residues 1-8 of SEQ ID NO: 14), wherein the composition is used in the manufacture of a medicament for the treatment of a blood cancer in a mammal by administering the medicament in a therapeutically effective amount.

2 . The composition of claim 1 comprising a peptide consisting of KGVSLSYRC (SEQ ID NO:14).

3 . The composition of claim 1 comprising a peptide consisting of KGVSLSYRCPCRFFESH (SEQ ID NO:13).

4 . A composition comprising a dimer having the peptide of claim 1 , 2 , or 3 , wherein the composition is used in the manufacture of a medicament for increasing hematopoietic cell multiplication in a mammal by administering the medicament in a therapeutically effective amount.

5 . The composition of claim 1 comprising a dimer consisting of SDF-1(1-8[P2G]) 2 .

6 . The composition of claim 1 comprising a dimer consisting of SDF-1(1-9[P2G]) 2 .

7 . The composition of claim 1 comprising a dimer consisting of:

wherein KGVSLSYR (SEQ ID NO: 3) is dimerized with the linker X.

8 . The composition of claim 1 comprising a dimer consisting of:

wherein KGVSLSYRC (SEQ ID NO: 4) is dimerized with the linker X.

9 . The composition of claim 1 comprising a dimer consisting of:

wherein KGVSLSYRCPCRFFESH (SEQ ID NO: 1) is dimerized using a linker X.

10 . The composition of claim 7 , 8 , or 9 , wherein the X comprises K.

11 . A composition comprising an SDF-1 analog that binds to a CXC chemokine receptor 4 (CXCR4), wherein the analog is selected from the group consisting of:
1) a first SDF-1 analog consisting of:
(i) an N-terminal region consisting of from 14 to about 17 amino acids that comprise a conserved KGVS (residues 1-4 in SEQ ID NO:1) motif in residue positions 1-4, and a conserved CPCRFF (residues 9-14 in SEQ ID NO:1) in residue positions 9-14;
(ii) a C-terminal region consisting of LKWIQEYLEKALN (residues 55-67 in SEQ ID NO:1); and
(iii) a linker consisting of either 4 natural amino acids or an aminoalkanoic acid having up to 20 carbons, where the linker connects the N-terminal region to the C-terminal region to form the SDF-1 analog; and
2) a second SDF-1 analog consisting of the first SDF-1 analog having conservative amino acid substitutions, wherein the conservative amino acid substitutions occur in any of residues 9-14 of the N-terminal region or the C-terminal region; wherein the first or second SDF-1 analog is optionally modified with an acyl group, acetyl group, an amide group, a detectable substance, a modifier capable of reducing the ability of the analog to act as a substrate for carboxypeptidases, or a modifier capable of reducing the ability of the analog to act as a substrate for aminopeptidases; and wherein the composition is used in the manufacture of a medicament for the treatment of a blood cancer in a mammal by administering the medicament in a therapeutically effective amount.

12 . The composition of claim 11 , wherein the N-terminal region of the SDF-1 analog consists of KGVSLSYRCPCRFF (residues 1-14 of SEQ ID NO:13).

13 . The composition of claim 11 , wherein the N-terminal region of the SDF-1 analog consists of KGVSLSYRCPCRFFESH (SEQ ID NO:13).

14 . The composition of claim 11 , wherein the linker is GGGG (residues 15-18 of SEQ ID NO: 74).

15 . The composition of claim 11 , wherein the C-terminal region of the SDF-1 analog is cyclized at residue positions corresponding to K 56 and E 60 of SEQ ID NO: 1.

16 . The composition of claim 11 , wherein the C-terminal region of the SDF-1 analog is cyclized at residue positions corresponding to E 60 and K 64 of SEQ ID NO:1.

17 . A composition comprising an SDF-1 analog that binds to a CXC chemokine receptor 4 (CXCR4), wherein the analog is selected from the group consisting of SEQ ID NOs: 74, 75, 137, 138, and 139, wherein the composition is used in the manufacture of a medicament for the treatment of a blood cancer in a mammal by administering the medicament in a therapeutically effective amount.

18 . A composition comprising an SDF-1 analog that binds to a CXC chemokine receptor 4 (CXCR4), wherein the analog consists of:
(i) an N-terminal region selected from the group consisting of:
a) residues 1-14 of SEQ ID NO:1,
b) residues 1-15 of SEQ ID NO:1,
c) residues 1-16 of SEQ ID NO:1, and
d) residues 1-17 of SEQ ID NO:1;
(ii) a C-terminal region consisting of LKWIQEYLEKALN (residues 55-67 in SEQ ID NO:1); and (iii) a linker consisting of either 4 natural amino acids or an aminoalkanoic acid having up to 20 carbons, where the linker connects the N-terminal region to the C-terminal region to form the SDF-1 analog; wherein the SDF-1 analog is optionally modified with an acyl group, acetyl group, an amide group, a detectable substance, a modifier capable of reducing the ability of the analog to act as a substrate for carboxypeptidases, or a modifier capable of reducing the ability of the analog to act as a substrate for aminopeptidases; and wherein the composition is used in the manufacture of a medicament for the treatment of a blood cancer in a mammal by administering the medicament in a therapeutically effective amount.

19 . The composition of claim 18 , wherein the C-terminal region of the SDF-1 analog is cyclized at residue positions corresponding to K 56 and E 66 of SEQ ID NO: 1.

20 . The composition of claim 18 , wherein the C-terminal region of the SDF-1 analog is cyclized at residue positions corresponding to E 66 and K 64 of SEQ ID NO: 1.

21 . The composition of claim 1 , wherein the blood cancer comprises a leukemia.

22 . The composition of claim 1 , wherein the blood cancer comprises acute myelogenous leukemia.

23 . The composition of claim 1 , wherein the blood cancer comprises a lymphoma.

24 . The composition of claim 1 , wherein the mammal is murine.

25 . The composition of claim 1 , wherein the mammal is human.

26 . A method of treating a blood cancer in a mammal, wherein the method comprises administering the composition of claim 1 to a mammal in a therapeutically effective amount.

27 . The method of claim 26 , wherein the blood cancer comprises a leukemia.

28 . The method of claim 26 , wherein the blood cancer comprises acute myelogenous leukemia.

29 . The method of claim 26 , wherein the blood cancer comprises a lymphoma.

30 . The method of claim 26 , wherein the mammal is murine.

31 . The method of claim 26 , wherein the mammal is human.

32 . A method of treating a blood cancer in a mammal, wherein the method comprises administering the composition of claim 7 to a mammal in a therapeutically effective amount.

33 . The method of claim 32 , wherein X is lysine.

34 . The method of claim 32 , wherein the blood cancer comprises a leukemia.

35 . The method of claim 32 , wherein the blood cancer comprises acute myelogenous leukemia.

36 . The method of claim 32 , wherein the blood cancer comprises a lymphoma.

37 . The method of claim 32 , wherein the mammal is murine.

38 . The method of claim 32 , wherein the mammal is human.

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