Claims
- 1. An analog of mpl ligand, wherein
- (a) said mpl ligand comprises a sequence of amino acids selected from the group consisting of amino acid sequences 7-151 through 1-332, inclusive of SEQ ID NO:2,
- (b) said analog of mpl ligand has at least one added N-linked glycosylation site in said sequence of amino acids,
- (c) said analog of mpl ligand has a biological activity of specifically stimulating or increasing megakaryocytes or platelets, and
- (d) said at least one added N-linked glycosylation site is selected from the group consisting of:
- (Asn164);
- (Asn163); and
- (Asn30, Thr32, Asn56, Asn120, Thr122, Asn164).
- 2. An analog of claim 1, wherein the mpl ligand has an amino acid sequence selected from the group consisting of:
- ______________________________________mpl ligand 1-332 amino acids 1-332 of SEQ ID NO: 2mpl ligand 1-199 amino acids 1-199 of SEQ ID NO: 2mpl ligand 1-191 amino acids 1-191 of SEQ ID NO: 2mpl ligand 1-183 amino acids 1-183 of SEQ ID NO: 2mpl ligand 1-174 amino acids 1-174 of SEQ ID NO: 2mpl ligand 7-332 amino acids 7-332 of SEQ ID NO: 2mpl ligand 7-191 amino acids 7-191 of SEQ ID NO: 2mpl ligand 7-199 amino acids 7-199 of SEQ ID NO: 2mpl ligand 7-183 amino acids 7-183 of SEQ ID NO: 2 andmpl ligand 7-174 amino acids 7-174 of SEQ ID NO: 2.______________________________________
- 3. An analog of claim 2, wherein the mpl ligand has an amino acid sequence consisting of amino acids 1-199 of SEQ ID NO: 2.
- 4. An analog of mpl ligand according to claim 2 which is;
- (Asn30, Thr32, Asn56, Asn120, Thr122, Asn164) mpl ligand 1-199 of SEQ ID NO:2.
- 5. An analog according to any one of claims 1-4, which is the product of expression of an exogenous DNA sequence in a eukaryotic cell.
- 6. An analog according to claim 5, wherein said eukaryotic cell is a mammalian cell.
- 7. An analog according to claim 6, wherein said mammalian cell is CHO.
- 8. A composition comprising an mpl ligand analog according to any one of claims 1-4 together with a pharmaceutically acceptable diluent, adjuvant or carrier.
Parent Case Info
This application is a continuation-in-part of U.S. Ser. No. 08/591,070, filed Feb. 9, 1996, now U.S. Pat. No. 5,756,083, which is a continuation-in-part of U.S. Ser. No. 08/388,779, filed Feb. 15, 1995, now U.S. Pat. No. 5,696,250, which is a divisional application of U.S. Ser. No. 08/451,086, filed May 25, 1995, each of which is incorporated herein by reference.
US Referenced Citations (2)
Number |
Name |
Date |
Kind |
5217881 |
Park |
Jun 1993 |
|
5218092 |
Sasaki et al. |
Jun 1993 |
|
Foreign Referenced Citations (14)
Number |
Date |
Country |
0 428 267 A2 |
Oct 1990 |
EPX |
0 668 352 A1 |
Aug 1995 |
EPX |
0 675 201 A1 |
Oct 1995 |
EPX |
2 714 670 A1 |
Jul 1995 |
FRX |
195 00 030 A1 |
Jul 1995 |
DEX |
WO 9505465 |
Feb 1995 |
WOX |
WO 9518858 |
Jul 1995 |
WOX |
WO 9521920 |
Aug 1995 |
WOX |
WO 9521919 |
Aug 1995 |
WOX |
WO 9526746 |
Oct 1995 |
WOX |
WO 9617062 |
Jun 1996 |
WOX |
WO 9625498 |
Aug 1996 |
WOX |
WO 9623888 |
Aug 1996 |
WOX |
WO 9814476 |
Apr 1998 |
WOX |
Non-Patent Literature Citations (3)
Entry |
Delorme et al., Biochemistry, 31:9871-9876 (1992). |
Eaton et al., "Biological Activity of Human Thrombopoietin (TPO), the C-mpl Ligand and TPO Variants and the Chromosomal Localization of TPO", Blood, 84(10), (1994); Abstract No. 948, XP 000567760. |
Hoffman, et al., "Peptide, disulfide, and glycosylation mapping of recombinant human thrombopoietin from Ser1 to Arg246", Biochemistry, 35(47), pp. 14849-14861, (1996). |
Divisions (1)
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Date |
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451086 |
May 1995 |
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Continuation in Parts (2)
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591070 |
Feb 1996 |
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Parent |
388779 |
Feb 1995 |
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