Methods of treating or preventing cell, tissue, and organ damage using human myeloid progenitor inhibitory factor-1 (MPIF-1)
AssigneeHuman Genome Sciences, Inc.
InventorsHaodong Li, Steven M. Ruben, Krzysztof J. Grzegorzewski, Craig A. Rosen, Vikram Patel, Reinder L. Gentz
Life of this patent
Estimating the term…
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.
Claims26
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.
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.
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.
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.
Dependencies are inferred from the claim text.