Claims
- 1. A method of treating or preventing cytotoxic agent-induced damage to cells, comprising administering to an individual an effective amount of the polypeptide of SEQ ID NO:2 or an active variant or fragment thereof, wherein said cells are selected from the group consisting of:
(a) cells of connective tissue, except for bone marrow stem cells, hematopoietic cells, and multipotential progenitor cells; (b) epithelial cells; (c) muscle cells; and (d) cells of the nervous system.
- 2. The method of claim 1, wherein said cells of connective tissue are selected from the group consisting of: skeletal system cells, osteoblasts, osteoclasts, osteocytes, chondrocytes, adipose cells, periosteal cells, endosteal cells, odontoblasts, blood cells, erythrocytes, leukocytes, eosinophils, basophils, neutrophils, lymphocytes, monocytes, thrombocytes, tissue macrophages, organ-specific phagocytes, B-lymphocytes, T-lymphocytes, megaloblasts, monoblasts, myeloblasts, lymphoblasts, proerythroblasts, megakaryoblasts, promonocytes, promyelocytes, prolymphocytes, early normoblasts, megakaryocytes, intermediate normoblasts, metamyelocytes, and late normoblasts.
- 3. The method of claim 1, wherein said individual is undergoing therapy that kills dividing cells.
- 4. The method of claim 3, wherein said therapy is selected from chemotherapy, radiation therapy, or targeted radiotherapy.
- 5. The method of claim 1, wherein said individual is undergoing occupational or accidental exposure to cytotoxic agents.
- 6. The method of claim 4, wherein said polypeptide is administered prior to said therapy.
- 7. The method of claim 4, wherein said polypeptide is administered during said therapy.
- 8. The method of claim 4, wherein said polypeptide is administered after said therapy.
- 9. The method of claim 5, wherein said polypeptide is administered prior to said exposure.
- 10. The method of claim 5, wherein said polypeptide is administered during said exposure.
- 11. The method of claim 5, wherein said polypeptide is administered after said exposure.
- 12. The method of claim 4, wherein said therapy is targeted radiotherapy.
- 13. The method of claim 12, wherein said targeted radiotherapy is radioimmunotherapy.
- 14. The method of claim 1, wherein said individual is undergoing intentional exposure to cytoxic agents.
- 15. The method of claim 14, wherein said cytoxic agent is radiation.
- 16. The method of claim 15, wherein said polypeptide is administered prior to said exposure.
- 17. The method of claim 15, wherein said polypeptide is administered during said exposure.
- 18. The method of claim 15, wherein said polypeptide is administered after said exposure.
- 19. The method of claim 15, wherein said radiation is due to a nuclear explosion.
- 20. The method of claim 19, wherein said individual has need of protection from or treatment for radiation sickness or radiation burns.
- 21. An isolated polypeptide comprising a member selected from the group consisting of:
(a) an analog of MPIF-1 comprising a deletion of amino acid residues selected from the amino terminus or the carboxy terminus of MPIF-1 shown in FIG. 1 (SEQ ID NO:2); (b) the analog of (a) wherein the deletion comprises a deletion of from at least one amino acid to about 52 amino acids, excluding deletions to amino acid residues 17, 22, 23, and 24, from the amino terminus of MPIF-1 shown in FIG. 1 (SEQ ID NO:2); (c) the analog of (a) wherein the deletion comprises a deletion of from at least one amino acid to about 52 amino acids from the carboxy terminus of MPIF-1 shown in FIG. 1 (SEQ ID NO:2); (d) the analog of (a) wherein the deletion comprises a deletion of from at least one amino acid to about 34 amino acids from the amino terminus and a deletion of from at least one amino acid to about 52 amino acids from the carboxy terminus of MPIF-1 shown in FIG. 1 (SEQ ID NO:2); (e) an analog of MPIF-1 comprising an addition of from at least one amino acid to about 100 amino acids to the amino terminus of the mature form of MPIF-1 shown in FIG. 1 (SEQ ID NO:2); (f) an analog of MPIF-1 comprising the amino acid sequence of FIG. 20 (SEQ ID NO:7); (g) an analog of MPIF-1 comprising the substitution of a different amino acid residue for one or more of the amino acid residues from about 21 to about 53 of MPIF-1 shown in FIG. 1 (SEQ ID NO:2); (h) the analog of (g) wherein the amino acid substitution(s) result in a polypeptide with a reduced positive charge.
- 22. A method of inhibiting proliferation of leukemia cells comprising administering an effective amount of the polypeptide of claim 21, wherein said polypeptide is conjugated to a therapeutic moiety.
- 23. The method of claim 22, wherein said therapeutic moiety is a radioisotope.
- 24. A method of protecting LPP-CFC cells comprising contacting such cells with an effective amount of the polypeptide of claim 21.
- 25. A method of protecting LPP-CFC cells comprising contacting such cells with an effective amount of a MPIF-1 polypeptide selected from the group consisting of:
(a) the amino acid sequence of the MPIF-1 polypeptide having the complete amino acid sequence in FIG. 1 (SEQ ID NO:2); (b) the amino acid sequence of the mature MPIF-1 polypeptide having the amino acid sequence at positions 22-120 in FIG. 1 (SEQ ID NO:2); (c) the amino acid sequence of the MPIF-1 polypeptide having the complete amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 75676; and contained in ATCC Deposit No. 75676.
- 26. An isolated polypeptide comprising a member of the group consisting of:
(a) a fragment of the amino acid sequence of SEQ ID NO:2; and (b) a fragment of the MPIF-1 amino acid sequence encoded by the cDNA in ATCC Deposit No. 75676; and wherein said fragment has an activity selected from the group consisting of: chemotactic activity for leukocytes, and inhibitory activity for bone marrow stem cell colony formation.
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a divisional of U.S. application Ser. No. 09/689,693, filed Oct. 13, 2000; said Ser. No. 09/689,693 claims the benefit of U.S. Provisional Appl. Nos. 60/159,362, filed Oct. 14, 1999, 60/164,059, filed Nov. 8, 1999, 60/172,063, filed Dec. 23, 1999, 60/189,048, filed Mar. 14, 2000, 60/199,142, filed Apr. 24, 2000, 60/211,458, filed Jun. 13, 2000 and 60/212,658, filed Jun. 19, 2000, and is a continuation-in-part of U.S. application Ser. No. 09/571,013, filed May 15, 2000 and a continuation-in-part of U.S. application Ser. No. 09/334,951, filed Jun. 17,1999, now U.S. Pat. No. 6,451,562; said Ser. No. 09/571,013 is a continuation of U.S. application Ser. No. 08/941,020, filed Sep. 30, 1997 (abandoned); said Ser. No. 08/941,020 claims the benefit of U.S. Provisional Appl. Nos. 60/027,299 and 60/027,300, both filed Sep. 30, 1996, and is a continuation-in-part of U.S. application Ser. No. 08/722,723, filed Sep. 30, 1996 (abandoned), and a continuation-in-part of U.S. application Ser. No. 08/722,719, filed Sep. 30, 1996, now U.S. Pat. No. 6,001,606; said Ser. No. 09/334,951 is a continuation of said Ser. No. 08/722,719; said Ser. No. 08/722,723 and said Ser. No. 08/722,719 is each a continuation-in-part of U.S. application Ser. No. 08/468,775, filed Jun. 6, 1995 (abandoned), and a continuation-in-part of U.S. application Ser. No. 08/465,682, filed Jun. 6, 1995 (abandoned), and a continuation-in-part of U.S. application Ser. No. 08/446,881, filed May 5, 1995 (abandoned); said Ser. No. 08/468,775 and said Ser. No. 08/465,682 is each a continuation of said Ser. No. 08/446,881 and a continuation-in-part of U.S. application Ser. No. 08/208,339, filed Mar. 8, 1994, now U.S. Pat. No. 5,504,003; said Ser. No. 08/446,881 is a continuation-in-part of said Ser. No. 08/208,339; each of said applications is herein incorporated by reference.
Provisional Applications (9)
|
Number |
Date |
Country |
|
60159362 |
Oct 1999 |
US |
|
60164059 |
Nov 1999 |
US |
|
60172063 |
Dec 1999 |
US |
|
60189048 |
Mar 2000 |
US |
|
60199142 |
Apr 2000 |
US |
|
60211458 |
Jun 2000 |
US |
|
60212658 |
Jun 2000 |
US |
|
60027299 |
Sep 1996 |
US |
|
60027300 |
Sep 1996 |
US |
Divisions (3)
|
Number |
Date |
Country |
Parent |
09689693 |
Oct 2000 |
US |
Child |
10261950 |
Oct 2002 |
US |
Parent |
09571013 |
May 2000 |
US |
Child |
10261950 |
Oct 2002 |
US |
Parent |
09334951 |
Jun 1999 |
US |
Child |
10261950 |
Oct 2002 |
US |
Continuations (3)
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Number |
Date |
Country |
Parent |
08722723 |
Sep 1996 |
US |
Child |
09571013 |
|
US |
Parent |
08722719 |
Sep 1996 |
US |
Child |
09571013 |
|
US |
Parent |
08208339 |
Mar 1994 |
US |
Child |
08465682 |
|
US |
Continuation in Parts (2)
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Number |
Date |
Country |
Parent |
08465682 |
Jun 1995 |
US |
Child |
08722719 |
|
US |
Parent |
08446881 |
May 1995 |
US |
Child |
08722719 |
|
US |