Methods to increase white blood cell survival after chemotherapy
AssigneeUniversity of Southern California
InventorsKathleen E. Rodgers, Gere DiZerega
Life of this patent
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Abstract
The present invention provides improved methods, kits, and pharmaceutical compositions for increasing white blood cell survival following chemotherapy, and mobilizing hematopoietic progenitor cells from bone marrow into peripheral blood, comprising the administration of an effective amount of angiotensinogen, angiotensin I (AI), AI analogues, AI fragments and analogues thereof, angiotensin II (AII), AII analogues, AII fragments or analogues thereof or AII AT2 type 2 receptor agonists.
Claims18
A method for increasing white blood cell survival following chemotherapy comprising the administration of an amount effective for increasing white blood cell survival following chemotherapy of at least one active agent comprising a sequence of the following general formula:
- Asp-Arg-R1-R2-Ile-His-Pro-R3 (SEQ ID NO:42),
- wherein
- R1 is selected from the group consisting of Val, Pro, Lys, norLeu, and Leu;
- R2 is selected from the group consisting of Ala, Tyr, and Tyr(PO3)2;
- R3 is Phe or is absent;
- and
- wherein the active agent is not SEQ ID NO:1.
A pharmaceutical composition for use in increasing white blood cell survival and/or mobilizing hematopoietic progenitor cells from bone marrow into peripheral blood following chemotherapy comprising
- (a) an amount effective for increasing white blood cell survival and/or mobilizing hematopoietic progenitor cells from bone marrow into peripheral blood following chemotherapy of at least one active agent comprising a sequence of the following general formula:
- Asp-Arg-R1-R2-Ile-His-Pro-R3 (SEQ ID NO:42),
- wherein
- R1 is selected from the group consisting of Val, Pro, Lys, norLeu, and Leu;
- R2 is selected from the group consisting of Ala, Tyr, and Tyr(PO3)2;
- R3 is Phe or is absent;
- and
- wherein the active agent is not SEQ ID NO:1;
- (b) an amount effective for decreasing the growth of tumor cells of a cytotoxic agent;
- and
- (c) a pharmaceutically acceptable carrier.
A method for increasing white blood cell survival following chemotherapy comprising the administration of an amount effective for increasing white blood cell survival following chemotherapy of at least one active agent consisting of a sequence of at least four contiguous amino acids of groups R1-R8 in the sequence of general formula I:
- R1-R2-R3-R4-R5-R6R7-R8
- wherein R1 is selected from the group consisting of Asp, Glu, Asn, Acpc (1-aminocyclopentane carboxylic acid), Ala, Me2Gly, Pro, Bet, Glu(NH2), Gly, Asp(NH2) and Suc,
- R2 is selected from the group consisting of Arg, Lys, Ala, Om, Ser(Ac), Sar, D-Arg and D-Lys;
- R3 is selected from the group consisting of Val, Ala, Leu, Lys, norLeu, Ile, Gly, Pro, Aib, Acpc, and Tyr;
- R4 is selected from the group consisting of Tyr, Tyr(PO3)2, Thr, Ser, Ala, homoSer, and azaTyr;
- R5 is selected from the group consisting of Ile, Ala, Leu, norLeu, Val and Gly;
- R6 is selected from the group consisting of His, Arg and 6-NH2-Phe;
- R7 is selected from the group consisting of Pro and Ala;
- R8 is selected from the group consisting of Phe, Phe(Br), Ile and Tyr;
- excluding sequences including R4 as a terminal Tyr group;
- and
- wherein the active agent is not SEQ ID NO:1.
A method for increasing white blood cell survival following chemotherapy comprising the administration of an amount effective for increasing white blood cell survival following chemotherapy of at least one active agent consisting of a sequence selected from the group consisting of angiotensinogen, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID,NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID. NO:40, and SEQ ID-NO:41.
A method for increasing white blood cell survival following chemotherapy comprising the administration of an amount effective for increasing white blood cell survival following chemotherapy of an active agent comprising the sequence of SEQ ID NO:4, wherein the active agent does not consist of the sequence of SEQ ID NO:1.
A pharmaceutical composition comprising:
- (a) an active agent consisting of a sequence of at least four contiguous amino acids of groups R1-R8 in the sequence of general formula I:
- R1-R2-R3-R4-R5-R6R7-R8
- wherein R1 is selected from the group consisting of Asp, Glu, Asn, Acpc (1-aminocyclopentane carboxylic acid), Ala, Me2Gly, Pro, Bet, Glu(NH2), Gly, Asp(NH2) and Suc,
- R2 is selected from the group consisting of Arg, Lys, Ala, Om, Ser(Ac), Sar, D-Arg and D-Lys;
- R3 is selected from the group consisting of Val, Ala, Leu, Lys, norLeu, Ile, Gly, Pro, Aib, Acpc, and Tyr;
- R4 is selected from the group consisting of Tyr, Tyr(PO3)2, Thr, Ser, Ala, homoSer, and azaTyr;
- R5 is selected from the group consisting of Ile, Ala, Leu, norLeu, Val and Gly;
- R6 is selected from the group consisting of His, Arg and 6-NH2-Phe;
- R7 is selected from the group consisting of Pro and Ala;
- R8 is selected from the group consisting of Phe, Phe(Br), Ile and Tyr;
- excluding sequences including R4 as a terminal Tyr group;
- and
- wherein the active agent is not SEQ ID NO:
- 1;
- (b) an amount effective for decreasing the growth of tumor cells of a cytotoxic agent;
- and
- (c) a pharmaceutically acceptable carrier.
A pharmaceutical composition comprising
- (a) an active agent consisting of a sequence selected from the group consisting of angiotensinogen, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:
- 16, SEQ ID NO:
- 17, SEQ ID NO:
- 18, SEQ ID NO:
- 19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, and SEQ ID NO:41;
- (b) an amount effective for decreasing the growth of tumor cells of a cytotoxic agent;
- and
- (c) a pharmaceutically acceptable carrier.
A pharmaceutical composition comprising
- (a) an active agent comprising the sequence of SEQ ID NO:4, wherein the active agent is not SEQ ID NO:1;
- (b) an amount effective for decreasing the growth of tumor cells of a cytotoxic agent;
- and
- (c) a pharmaceutically acceptable carrier.
Dependencies are inferred from the claim text.