Hematopoietic stem cell growth-promoting compositions containing a fibroblast-derived fragment of fibronectin and a growth factor, and methods employing them in vitro or in vivo

• US 5,668,104 A
• Filed: 04/26/1994
• Issued: 09/16/1997
• Est. Priority Date: 03/31/1992
• Status: Expired due to Fees

• Current Assignee: Toray Industries Incorporated
• Original Assignee: Toray Industries Incorporated
• Inventors: Nakahata, Tatsutoshi, Sudo, Tetsuo, Kojima, Katsuaki, Kawano, Genji
• Primary Examiner(s): Walsh, Stephen G.
• Assistant Examiner(s): Fitzgerald, David L.
• Application Number:
  US08/142,449
• Time in Patent Office: 1,239 Days
• Field of Search: 530/380, 530/381, 530/350, 530/351, 530/395, 435/69.1, 435/240.2, 435/252.3, 435/254.11, 514/2, 514/8, 424/85.1
• US Class Current: 424/85.2
• 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: C07K 14/475 Growth factors; Growth regulators

Abstract

An 18 kDa protein, denominated FDF-3, has been isolated from cultures of human fibroblasts and has been found to potentiate the growth- and differentiation-promoting activities of certain cytokines toward hematopoietic progenitor cells. The amino acid sequence of the FDF-3 protein, shown in SEQ ID NO: 14, corresponds to the sequence of a C-terminal domain of human fibronectin. The protein is useful in combination with IL-3, G-CSF, GM-CSF, or SCF (stem cell factor) in the expansion of hematopoietic cell populations in vitro or in therapeutic methods to promote recovery from leukopenia or myelosuppresion in vivo.

Claims

1. A therapeutic composition comprising:

an FDF-3 polypeptide having a molecular weight of 18±

2 kDa as determined by SDS-PAGE and having an amino acid sequence which comprises residues 1-162 as set forth in SEQ ID NO;

14; and

a cytokine selected from the group consisting of IL-3, G-CSF, GM-CSF, and stem cell factor.

2. A composition according to claim 1, wherein the FDF-3 polypeptide has the amino acid sequence shown as residues 1-162 of SEQ ID NO:

14.

3. A composition according to claim 1, wherein the FDF-3 polypeptide has the amino acid sequence shown as residues 1-163 of SEQ ID NO:

14.

4. A composition according to claim 1, wherein the FDF-3 polypeptide has the amino acid sequence shown as residues 1-164 of SEQ ID NO:

14.

5. A composition according to claim 1, wherein the FDF-3 polypeptide has the amino acid sequence shown as residues 1-165 of SEQ ID NO:

14.

6. A composition according to claim 1, wherein the FDF-3 polypeptide has the amino acid sequence shown as residues 1-166 of SEQ ID NO:

14.

7. A composition according to claim 1, wherein the FDF-3 polypeptide has the amino acid shown as residues 1-167 of SEQ ID NO:

14.

8. A composition according to claim 1, wherein the FDF-3 polypeptide has the amino acid sequence shown as residues 1-168 of SEQ ID NO:

14.

9. A composition according to claim 1, wherein the FDF-3 polypeptide has the amino acid sequence shown as residues 1-188 of SEQ ID NO:

14.

10. A method for promoting the growth and differentiation of hematopoietic progenitor cells, comprising the step of contacting a population of progenitor cells with a composition according to any one of claims 1-9.

11. A method according to claim 10, wherein said progenitor cells are present in a patient and the method comprises the step of administering said composition to said patient.