Mpl ligand (thrombopoietin), nucleic acids encoding such, and methods of treatment using mpl ligand
AssigneeGenentech, Inc.
InventorsDan L. Eaton, Frederic J. de Sauvage
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Abstract
Isolated thrombopoietin (TPO), isolated DNA encoding TPO, and recombinant or synthetic methods of preparing and purifying TPO are disclosed. Various forms of TPO are shown to influence the replication, differentiation or maturation of blood cells, especially megakaryocytes and megakaryocyte progenitor cells. Accordingly, these compounds may be used for treatment of thrombocytopenia.
Claims22
An isolated substantially homogeneous mpl ligand having thrombopoietic activity and having at least 70% sequence identity with the human mpl ligand amino acid sequence from Cys7 through Cys151 inclusive (hML(7-151) as shown in SEQ ID NO.:
- 1.
A human mpl ligand fragment, comprising one or more amino acid sequences selected from the group consisting of
- SPAPPACDLRVLSKLLRDSHVL as shown in SEQ ID NO.:
- 110,
- HSRLSQCPEVHPLPTPVLLPAVDF as shown in SEQ ID NO.:
- 111,
- SLGEWKTQMEETKAQDILGAVTL as shown in SEQ ID NO.:
- 112,
- LLEGVMAARGQLGPTCLSSLL as shown in SEQ ID NO.:
- 113,
- GQLSGQVRLLLGALQS as shown in SEQ ID NO.:
- 114,
- LLGTQLPPQGRTTAHKDPNAIF as shown in SEQ ID NO.:
- 115, and
- LSFWHLLRGKVRFLMLVGGSTLCVR as shown in SEQ ID NO.:
- 116.
An isolated nucleic acid molecule comprising the open reading frame nucleic acid sequence shown in SEQ ID NO.:
- 2.
A process for the biosynthesis of a human mpl ligand having thrombopoietic activity and having at least 70% sequence identity with the human mpl ligand amino acid sequence from Cys7 through Cys151 inclusive as shown in SEQ ID NO.:
- 1, comprising
- (a) growing a host cell culture containing DNA encoding the human mpl ligand,
- (b) recovering the human mpl ligand from the culture, and
- (c) purifying the mpl ligand so as to obtain substantially homogeneous human mpl ligand having thrombopoietic activity.
A method of treating a human having or at risk of thrombocytopenia comprising administering to the human in need of such treatment a sterile composition comprising a physiologically acceptable vehicle, carrier, excipient, or stabilizer and a thrombopoietin molecule capable of binding to and activating human mpl selected from the group consisting of:
- (a) substantially homogeneous human thrombopoietin comprising the hML amino acid sequence from Cys7 through Cys151 inclusive as shown in SEQ ID NO.:
- 1;
- and
- (b) Substantially homogeneous thrombopoietin having an amino acid sequence that is at least 95% identical to the human thrombopoietin in (a).
Dependencies are inferred from the claim text.