Methods of inhibiting hematopoietic stem cells using human myeloid progenitor inhibitory factor-1 (MPIF-1) (Ckbeta-8/MIP-3)

• US 6,495,129 B1
• Filed: 10/13/2000
• Issued: 12/17/2002
• Est. Priority Date: 03/08/1994
• Status: Expired due to Fees

• Current Assignee: Human Genome Sciences Incorporated (GlaxoSmithKline PLC)
• Original Assignee: Human Genome Sciences Incorporated (GlaxoSmithKline PLC)
• Inventors: Ruben, Steven M., Li, Haodong
• Primary Examiner(s): MERTZ, PREMA MARIA
• Application Number:
  US09/689,693
• Time in Patent Office: 795 Days
• Field of Search: 424/85.1, 424/885, 514/2, 514/8, 514/12
• US Class Current: 424/85.1
• CPC Class Codes: A61K 2121/00 Preparations for use in therapy
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 41/0038 Radiosensitizing, i.e. administration of pharmaceutical agents that enhance the effect of radiotherapy radiotherapy per se A61N5/10
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: C07K 1/113 without change of the primary structure
• CPC Class Codes: C07K 1/36 by a combination of two or more processes of different types
• CPC Class Codes: C07K 14/50 Fibroblast growth factor [FGF]
• CPC Class Codes: C07K 14/521 Chemokines
• CPC Class Codes: C07K 14/523 Beta-chemokines, e.g. RANTES, I-309/TCA-3, MIP-1alpha, MIP-1beta/ACT-2/LD78/SCIF, MCP-1/MCAF, MCP-2, MCP-3, LDCF-1, LDCF-2
• CPC Class Codes: C07K 16/24 against cytokines, lymphokines or interferons
• CPC Class Codes: C07K 2319/00 Fusion polypeptide
• CPC Class Codes: C12N 15/72 Expression systems using regulatory sequences derived from the lac-operon
• CPC Class Codes: C12N 2799/026 where the vector is derived from a baculovirus

Abstract

There are disclosed therapeutic compositions and methods using isolated nucleic acid molecules encoding a human myeloid progenitor inhibitory factor-1 (MPIF-1) polypeptide (previously termed MIP-3 and chemokine β8 (CKβ8 or ckb-8)), as well as MPIF-1 polypeptide itself, as are vectors, host cells and recombinant methods for producing the same.

Claims

1. A method for inhibiting bone marrow stem cells, comprising:

(a) administering to a subject in need thereof a polypeptide comprising a fragment of the amino acid sequence of SEQ ID NO;

2, wherein said fragment comprises the conserved Cys residues at positions 54 and 94 of SEQ ID NO;

2 and inhibits bone marrow stem cells; and

thereby

(b) inhibiting bone marrow stem cells in said subject.

2. The method of claim 1, wherein said polypeptide comprises a heterologous polypeptide.

3. The method of claim 1, wherein said polypeptide is administered to protect hematopoietic stem cells during cancer chemotherapy.

4. The method of claim 1, wherein said polypeptide is administered in combination with a pharmaceutically acceptable carrier.

5. The method of claim 1, wherein said polypeptide comprises a Met residue at the N-terminus.

6. The method of claim 5, wherein said polypeptide comprises a heterologous polypeptide.

7. The method of claim 5, wherein said polypeptide is administered to protect hematopoietic stem cells during cancer chemotherapy.

8. The method of claim 5, wherein said polypeptide is administered in combination with a pharmaceutically acceptable carrier.

9. A method for inhibiting bone marrow stem cells, comprising:

(a) administering to a subject in need thereof a polypeptide comprising a fragment of human myeloid progenitor inhibitory factor-1 (MPIF-1) amino acid sequence encoded by the cDNA in ATCC Deposit No. 75676, wherein said fragment comprises the conserved Cys residues at posidbns 54 and 94 of SEQ ID NO;

2 and inhibits bone marrow stem cells; and

thereby

(b) inhibiting bone marrow stem cells in said subject.

10. The method of claim 9, wherein said polypeptide comprises a heterologous polypeptide.

11. The method of claim 9, wherein said polypeptide is administered to protect hematopoietic stem cells during cancer chemotherapy.

12. The method of claim 9, wherein said polypeptide is administered in combination with a pharmaceutically acceptable carrier.

13. The method of claim 9, wherein said polypeptide comprises a Met residue at the N-terminus.

14. The method of claim 13, wherein said polypeptide comprises a heterologous polypeptide.

15. The method of claim 13, wherein said polypeptide is administered to protect hematopoietic stem cells during cancer chemotherapy.

16. The method of claim 13, wherein said polypeptide is administered in combination with a pharmaceutically acceptable carrier.