干细胞领域知识发现平台

提升科研信息化水平
支撑研究所科技创新

  融合多源信息    打通数据孤岛
  挖掘知识关联    放大数据价值
  集成知识计算    促进知识发现

免费注册账号
查看全文和研发动态、知识导航以及收藏您喜欢的数据等操作,您需要注册一个免费帐户并登录。

写笔记

您最近的笔记
Inhibitor and stimulator of stem cell proliferation and uses thereof
公开时间: 1999-03-29
申请时间: 1998-04-01
申请号: ZA19980002746
发明专利

ZA9802746A

摘要


主权项

WHAT IS CLAIMED IS:| 1. A polypeptide comprising hemoglobin alpha chain wherein the C-terminal hydrophobic domain has been substituted or deleted.| 2. A polypeptide comprising hemoglobin alpha chain wherein the C-terminal haptoglobin-binding domain has been substituted or deleted.| 3. A polypeptide comprising amino acids 1-97 of the human alpha hemoglobin chain.| 4. A pharmaceutical composition comprising (a) a polypeptide as in claim 1 or 2 and (b) a pharmaceutically acceptable carrier.| 5. A pharmaceutical composition comprising a polypeptide consisting of amino acids 1-97 of the human alpha hemoglobin chain and a pharmaceutically acceptable carrier.| 6. A pharmaceutical composition comprising a polypeptide consisting of amino acids 1-94 of the human alpha hemoglobin chain and a pharmaceutically acceptable carrier.| 7. A pharmaceutical composition as in claim 4-6 in unit dosage form.| 8. A pharmaceutical composition as in claim 7 comprising 0.1 mgs. to 6 gms. of one or two compounds selected from the group consisting of a polypeptide having the sequence of amino acids 1-97 of the human alpha hemoglobin chain and a polypeptide having the sequence of amino acids 1-94 of the human alpha hemoglobin chain.| 110| 9. The use of a polypeptide of either one of claims 1 or 2 in the preparation of a medicament for use in a method of inhibiting stem cell proliferation.| 10. The use as in claim 9 wherein said polypeptide is selected from the group consisting of a polypeptide having the sequence of amino acids 1-97 of the human alpha hemoglobin chain, a polypeptide having the sequence of amino acids 1-94 of the human alpha hemoglobin chain and a peptide having the sequence Phe-Leu-Gly-Phe-Pro-Thr.| 11. The use of a polypeptide of either one of claims 1 or 2 in the preparation of a medicament for use in a method of stimulating the growth of B cells.| 12. The use of a polypeptide of either one of claims 1 or 2 in the preparation of a medicament for use in a method of treating cancer in a mammal suffering therefrom which method comprises the steps of:| a) administering radiotherapy or chemotherapy, and b) administering a medicament with a stem cell proliferation inhibiting amount of a polypeptide as in claim 1 or 2.| 13. The use as in claim 12 wherein said polypeptide is selected from the group consisting of a polypeptide having the sequence of amino acids 1-97 of the human alpha hemoglobin chain and a polypeptide having the sequence of amino acids 1-94 of the human alpha hemoglobin chain.| 14. The use as in claim 12 wherein steps a and b are repeated one or more times.| 15. The use as in claim 12 wherein step a is conducted after step b.| Ill| 16. The use as in claim 12 wherein step b is conducted within 24 hours before or after step a.| 17. A method for treating cancer in a mammal comprising:| a) removing hematopoietic cells from said mammal,| b) treating said hematopoietic cells ex vivo with a preparation comprising a polypeptide as in claim 1 or 2,| c) treating said hematopoietic cells of step b with chemotherapy or radiation,| d) performing myeloablative treatment on said mammal, and e) transplanting into said mammal the hematopoietic cells of step c.| 18. A method as in claim 17 wherein said polypeptide in step (b) is selected from the group consisting of a polypeptide having the sequence of amino acids 1-97 of the human alpha hemoglobin chain and a polypeptide having the sequence of amino acids 1-94 of the human alpha hemoglobin chain.| 19. The use of a polypeptide as in claim 1 or 2 in the preparation of a medicament for use in a method of inhibiting stem ceil division in a mammal exposed to an agent which damages or destroys stem cells.| 20. The use as in claim 19 wherein said polypeptide is selected from the group consisting of a polypeptide having the sequence of amino acids 1-97 of the human alpha hemoglobin chain, a polypeptide having the sequence of amino acids 1-94 of the human alpha hemoglobin chain and a peptide having the sequence Phe-Leu-Gly-Phe-Pro-Thr.| 21. The use as in claim 19 wherein said agent is an antiviral agent.| 112| 22. A method of maintaining mammalian hematopoietic stem cells ex vivo comprising contacting hematopoietic cells with a stem cell proliferation inhibiting amount of a polypeptide as in claim 1 or 2.| 23. A method as in claim 22 wherein said polypeptide is selected from the group consisting of a polypeptide having the sequence of amino acids 1-97 of the human alpha hemoglobin chain, a polypeptide having the sequence of amino acids 1-94 of the human alpha hemoglobin chain chain, and a peptide having the sequence Phe-Leu-Gly-Phe-Pro-Thr.| 24. A method as in claim 22 wherein said hematopoietic cells are selected from the group consisting of bone marrow cells, peripheral blood cells, mobilized peripheral blood cells, fetal liver and umbilical cord blood cells.| 25. The use of a polypeptide as in claim 1 or 2 in the preparation of a medicament for use in a method of treating a myeloproliferative or autoimmune disease or epithelial stem cell hyperproliferation in a mammal suffering therefrom.| 26. The use as in claim 25 wherein said myeloproliferative disease is a myelodysplastic syndrome.| 27. The use of a polypeptide as in claim 1 or 2 in the preparation of a medicament for use in a method for differentially protecting normal stem cells and not cancer cells in a mammal from chemotherapy or radiation.| 113| 28. The use as in claim 27 wherein said polypeptide is selected from the group consisting of a polypeptide having the sequence of amino acids 1-97 of the human alpha hemoglobin chain, a polypeptide having the sequence of amino acids 1-94 of the human alpha hemoglobin chain, and a peptide having the sequence Phe-Leu-Gly-Phe-Pro-Thr.| 29. The use as in claim 27 wherein said polypeptide is administered after said normal stem cells are induced to proliferate by exposure to a cytotoxic drug or radiation.| 30. The use of a polypeptide as in claim 1 or 2 in the preparation of an adjuvant for use in a method of vaccinating a mammal by administering the adjuvant before, during or after administration of a vaccine.| 31. The use of a polypeptide as in claim 1 or 2 in the preparation of a medicament for use in a method of treating a mammal having immunodepression caused by stem cell hyperproliferation.| 32. A method of conducting gene therapy in a mammal comprising:| a) removing hematopoietic cells from said mammal,| b) transfecting said hematopoietic cells with a predetermined gene,| c) contacting said transfected hematopoietic cells ex vivo with a preparation comprising a polypeptide as in claim 1 or 2,| d) transplanting into said mammal the hematopoietic cells of step c.| 33. A method as in claim 32 wherein said polypeptide in step (c) is selected from the group consisting of a polypeptide having the sequence of amino acids 1-97 of the human alpha hemoglobin chain and a polypeptide having the sequence of amino acids 1-94 of the human alpha hemoglobin chain.| 114| • •| 34. A method as in claim 32 further comprising after step (a) treating said hematopoietic cells with at least one stimulatory cytokine to induce stem cell proliferation.| 35. A method as in claim 32 further comprising after step (d) treating the mammal in vivo with said polypeptide.| 36. A method for conducting ex vivo stem cell expansion comprising contacting hematopoietic cells with a polypeptide as in claim 1 or 2 and at least one stimulatory cytokine.| 37. A method as in claim 36 wherein said polypeptide is selected from the group consisting of a polypeptide having the sequence of amino acids 1-97 of the human alpha hemoglobin chain and a polypeptide having the sequence of amino acids 1-94 of the human alpha hemoglobin chain.| 38. A method as in claim 36 wherein said hematopoietic cells are cells selected from the group consisting of bone marrow cells, peripheral blood cells, mobilized peripheral blood cells, fetal liver and umbilical cord blood cells.| 39. A pharmaceutical composition comprising (a) a polypeptide as in claim 1 or 2 and (b) at least one inhibitory compound selected from the group consisting of MIP-la, TGFj3, TNFa, INFa, INFp, INFy, the pentapeptide pyroGlu-Glu-Asp-Cys-Lys, the tetrapeptide N-Acetyl-Ser-Asp-Lys-Pro, and the tripeptide glutathione (Gly-Cys-^Glu).| 40. A composition as in claim 39 wherein said polypeptide is selected from the group consisting of a polypeptide having the sequence of amino acids 1-97 of the human alpha hemoglobin chain and a polypeptide having the sequence of amino acids 1-94 of the human alpha hemoglobin chain.| 115| 41. A pharmaceutical composition comprising (a) a polypeptide as in claim 1 or 2 and (b) at least one stimulatory compound selected from the group consisting of IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-9, IL-11, IL-13, IL-14, IL-15, G-CSF, GM-CSF, M-CSF, erythropoietin, thrombopoietin, stem cell factor, and flk2/flt3 ligand.| 42. A composition as in claim 41 wherein said polypeptide is selected from the group consisting of a polypeptide having the sequence of amino acids 1-97 of the human alpha hemoglobin chain and a polypeptide having the sequence of amino acids 1-94 of the human alpha hemoglobin chain.| 43. A method for expressing alpha hemoglobin or substitution or deletion analogs thereof comprising expressing said alpha hemoglobin or substitution or deletion analogs as a ubiquitin fusion.| 44. A method as in claim 43 wherein said expressing step is done in E. coli.| 45. A method as in claim 43 wherein said expressing step includes expressing a ubiquitin cleaving enzyme.| 46. A peptide having the sequence selected from the group consisting of biotin-Phe-Pro-His-Phe-Asp-Leu-Ser-His-Gly-Ser-Ala-Gln-Val, (iodo)Phe-Pro-His-Phe-Asp-Leu-Ser-His-Gly-Ser-Ala-Gln-Val, Phe-Pro-His-(iodo)Phe-Asp-Leu-Ser-His-Gly-Ser-Ala-Gln-Val and (iodo)Phe-Pro-His-(iodo)Phe-Asp-Leu-Ser-His-Gly-Ser-Ala-Gln-Val.| 116| 47. A method of stimulating stem cell proliferation comprising contacting hematopoietic cells with a stem cell proliferation stimulating amount of INPROL and/or an opiate compound.| 48. A method as in claim 47 wherein said INPROL is selected from the group consisting of the alpha chain of hemoglobin,the beta chain of hemoglobin,the gamma chain of hemoglobin, the delta chain of hemoglobin, the epsilon chain of hemoglobin, the zeta chain of hemoglobin,| a polypeptide having the sequence of amino acids 1-97 of the human alpha hemoglobin chain, and a polypeptide having the sequence of amino acids 1-94 of the human alpha hemoglobin chain.| 49. A method as in claim 47 wherein said INPROL is selected from the group consisting of peptides having the sequence: Phe-Pro-His-Phe-Asp-Leu-Ser-His-Gly-Ser-Ala-Gln-Val, Cys-Phe-Pro-His-Phe-Asp-Leu-Ser-His-Gly-Ser-Ala-Gln-Val-Cys| (where the two Cys residues form a disulfide bond), Asp-Ala-Leu-Thr-Asn-Ala-Val-Ala-His-Val-Asp-Asp-Met-Pro-Asn-Ala-Leu-Ser-Ala, Phe-Leu-Gly-Phe-Pro-Thr,| Leu-V al-V al-Tyr-Pro-Trp-Thr-Gln-Arg-Phe,| Leu-Val-Val-Tyr-Pro-Trp-Thr-Gln-Arg,| Leu-Val-Val-Tyr-Pro-Trp-Thr-Gln,| Leu-Val-Val-Tyr-Pro-Trp-Thr,| Leu-Val-V al-T yr-Pro-Trp,| Leu-Val-V al-T yr-Pro,| Val-Val-Tyr-Pro-Trp-Thr-Gln,| 117| Tyr-Pro-Trp-Thr-Gln-Arg-Phe,| Tyr-Pro-Trp-Thr-Gln-Arg,| Tyr-Pro-Trp-Thr-Gln, and Tyr-Pro-Trp-Thr.| 50. A method as in claim 47 wherein said opiate compound is selected from the group consisting of morphine, etorphine, codeine, heroin, hydromorphone, oxymorphone, levorphanol, levallorphan, codeine, hydrocodone, oxycodone, nalorphine, naloxone, naltrexone, buprenorphine, butanorphanol, nalbuphine, meperidine, alphaprodine, diphenoxylate, fentanyl, DAMGO, DALDA and nociceptin.| 51. A method of stimulating stem cell proliferation comprising contacting hematopoietic cells with a compound capable of binding opiate receptors.| 52. A method as in claim 51 wherein said compound has selectivity for the mu subclass of opiate receptor.| 53. A method of stimulating or inhibiting stem cell proliferation comprising contacting hematopoietic cells with a compound capable of binding nociceptin receptors.| 54. A method of stimulating or inhibiting stem cell proliferation comprising contacting hematopoietic cells with a compound capable of activating the Ginhibitory subclass of GTP binding proteins.| 55. A method of stimulating or inhibiting stem cell proliferation comprising contacting hematopoietic cells with a compound capable of binding to an opiate-like receptor not including the classical mu, kappa or delta opiate receptors or ORL1, wherein| 118| said receptor (a) has stem cell stimulating and/or inhibiting properties and (b) has said stem cell stimulating and/or inhibiting ability antagonizable by naloxone.| 56. A method as in claim 55 wherein said opiate-like receptor has the ability to bind the peptide Phe-Pro-His-Phe-Asp-Leu-Ser-His-Gly-Ser-Ala-Gin-Val with a dissociation constant (K<j) less than or equal to 1 micromolar.| 57. A method as in claim 55 wherein the dissociation constant is less than or equal to 10 nanomolar.| 58. A method of identifying a receptor for INPROL comprising contacting a material which contains said receptor with INPROL in a receptor-binding assay.| 59. A method as in method 58 wherein said INPROL is selected from the group the alpha chain of hemoglobin,the beta chain of hemoglobin,the gamma chain of hemoglobin,| the delta chain of hemoglobin, the epsilon chain of hemoglobin, the zeta chain of hemoglobin,| a polypeptide having the sequence of amino acids 1-97 of the human alpha hemoglobin chain,| a polypeptide having the sequence of amino acids 1-94 of the human alpha hemoglobin chain,| Phe-Pro-His-Phe-Asp-Leu-Ser-His-Gly-Ser-Ala-Gln-Val, biotin-Phe-Pro-His-Phe-Asp-Leu-Ser-His-Gly-Ser-Ala-Gln-Val, (iodo)Phe-Pro-His-Phe-Asp-Leu-Ser-His-Gly-Ser-Ala-Gln-Val, Phe-Pro-His-(iodo)Phe-Asp-Leu-Ser-His-Gly-Ser-Ala-Gln-Val, (iodo)Phe-Pro-His-(iodo)Phe-Asp-Leu-Ser-His-Gly-Ser-Ala-Gln-Val,| 119| Cys-Phe-Pro-His-Phe-Asp-Leu-Ser-His-Gly-Ser-Ala-Gin-Val-Cys, and Asp-Ala-Leu-Thr-Asn-Ala-Val-Ala-His-Val-Asp-Asp-Met-Pro-Asn-Ala-Leu-Ser-Ala.| 60. A method of identifying a receptor for INPROL comprising contacting a material which contains said receptor with INPROL in an adenylate cyclase assay.| 61. A method as in method 60 wherein said INPROL is selected from the group the alpha chain of hemoglobin,the beta chain of hemoglobin,the gamma chain of hemoglobin, the delta chain of hemoglobin, the epsilon chain of hemoglobin, the zeta chain of hemoglobin a polypeptide having the sequence of amino acids 1-97 of the human alpha hemoglobin chain,| a polypeptide having the sequence of amino acids 1-94 of the human alpha hemoglobin chain,| Phe-Pro-His-Phe-Asp-Leu-Ser-His-Gly-Ser-AIa-Gln-Val, biotin-Phe-Pro-His-Phe-Asp-Leu-Ser-His-Gly-Ser-Ala-Gin-Val, (iodo)Phe-Pro-His-Phe-Asp-Leu-Ser-His-Gly-Ser-Ala-Gln-Val, Phe-Pro-His-(iodo)Phe-Asp-Leu-Ser-His-Gly-Ser-Ala-Gln-Val, (iodo)Phe-Pro-His-(iodo)Phe-Asp-Leu-Ser-His-Gly-Ser-Ala-Gln-Val, Cys-Phe-Pro-His-Phe-Asp-Leu-Ser-His-Gly-Ser-Ala-Gln-Val-Cys, and Asp-Ala-Leu-Thr-Asn-Ala-Val-Ala-His-Val-Asp-Asp-Met-Pro-Asn-Ala-Leu-Ser-Ala.| 62. The use of INPROL and/or an opiate compound in the preparation of a medicament for use in a method of treating cancer in a mammal suffering therefrom comprising the steps of:| a) administering radiotherapy and/or chemotherapy, and b) administering a medicament with stem cell proliferation stimulatory amount of INPROL and/or an opiate compound.| 1on| 63. The use as in claim 62 wherein steps a and b are repeated one or more times.| 64. The use as in claim 62 wherein step a is conducted before step b.| 65. The use as in claim 62 wherein said opiate compound is selected from the group of morphine, etorphine, codeine, heroin, hydromorphone, oxymorphone, levorphanol, levallorphan, codeine, hydrocodone, oxycodone, nalorphine, naloxone, naltrexone, buprenorphine, butanorphanol, nalbuphine, meperidine, alphaprodine, diphenoxylate, fentanyl, DAMGO, DALDA and nociceptin..| 66. The use of INPROL and/or an opiate compound in the preparation of a medicament for use in a method of stimulating stem cell division in a mammal exposed to an agent which damages or destroys stem cells.| 67. The use as in claim 66 wherein said agent is an antiviral agent or an antineoplastic agent.| 68. The use as in claim 66 wherein said opiate compound is selected from the group of morphine, etorphine, codeine, heroin, hydromorphone, oxymorphone, levorphanol, levallorphan, codeine, hydrocodone, oxycodone, nalorphine, naloxone, naltrexone, buprenorphine, butanorphanol, nalbuphine, meperidine, alphaprodine, diphenoxylate, fentanyl, DAMGO, DALDA and nociceptin.| 69. A method of maintaining mammalian hematopoietic stem cells ex vivo comprising contacting hematopoietic cells with a stem cell proliferation stimulating amount of INPROL and/or an opiate compound.| 121| 70. A method as in claim 69 wherein said hematopoietic cells are selected from the group consisting of bone marrow cells, peripheral blood cells, mobilized peripheral blood cells, fetal liver and umbilical cord blood cells.| 71. A method as in claim 69 wherein said opiate compound is selected from the group of morphine, etorphine, codeine, heroin, hydromorphone, oxymorphone, levorphanol, levallorphan, codeine, hydrocodone, oxycodone, nalorphine, naloxone, naltrexone, buprenorphine, butanorphanol, nalbuphine, meperidine, alphaprodine, diphenoxylate, fentanyl, DAMGO, DALDA and nociceptin.| 72. The use of INPROL and/or an opiate compound in the preparation of a medicament for use in a method of treating a myeloproliferative disease, hematopoieitic or epithelial stem cell hypoproliferation in a mammal suffering therefrom.| 73. The use . as in claim 72 wherein said myeloproliferative disease is a myelodysplastic syndrome or aplastic anemia.| 74. The use as in claim 72 wherein said opiate compound is selected from the group of morphine, etorphine, codeine, heroin, hydromorphone, oxymorphone, levorphanol, levallorphan, codeine, hydrocodone, oxycodone, nalorphine, naloxone, naltrexone, buprenorphine, butanorphanol, nalbuphine, meperidine, alphaprodine, diphenoxylate, fentanyl, DAMGO, DALDA and nociceptin.| 75. The use of INPROL and/or an opiate compound in the preparation of a medicament for use in a method for treating or preventing stem cell exhaustion.| 122| 76. The use as in claim 75 wherein said stem cell exhaustion is due to an acquired immune deficiency syndrome.| 77. The use as in claim 75 wherein said opiate compound is selected from the group of morphine, etorphine, codeine, heroin, hydromorphone, oxymorphone, levorphanol, levallorphan, codeine, hydrocodone, oxycodone, nalorphine, naloxone, naltrexone, buprenorphine, butanorphanol, nalbuphine, meperidine, alphaprodine, diphenoxylate, fentanyl, DAMGO, DALDA and nociceptin.| 78. The use of an opiate compound in the preparation of a medicament for use in a method for differentially protecting normal stem cells in a mammal from chemotherapy or radiation.| 79. The use as in claim 78 wherein said opiate compound is selected from the group of morphine, etorphine, codeine, heroin, hydromorphone, oxymorphone, levorphanol, levallorphan, codeine, hydrocodone, oxycodone, nalorphine, naloxone, naltrexone, buprenorphine, butanorphanol, nalbuphine, meperidine, alphaprodine, diphenoxylate, fentanyl, DAMGO, DALDA and nociceptin.| 80. A method of conducting gene therapy in a mammal comprising:| a) removing hematopoietic cells from said mammal,| b) treating said hematopoietic cells ex vivo with a stem cell stimulatory amount of INPROL and/or an opiate compound,| c) transfecting or infecting said hematopoietic cells with a predetermined gene,| d) contacting said transfected hematopoietic cells ex vivo with a stem cell inhibitory amount of INPROL and/or an opiate compound,| 123| e) transplanting into said mammal the hematopoietic cells of step d f) optionally treating said mammal in vivo with a stem cell inhibitory or stimulatory quantity INPROL and/or an opiate compound.| 81. A method as in claim 80 wherein said opiate compound is selected from the group of morphine, etorphine, codeine, heroin, hydromorphone, oxymorphone, levorphanol, levallorphan, codeine, hydrocodone, oxycodone, nalorphine, naloxone, naltrexone, buprenorphine, butanorphanol, nalbuphine, meperidine, alphaprodine, diphenoxylate, fentanyl, DAMGO, DALDA and nociceptin.| 82. A method for conducting ex vivo stem cell expansion comprising contacting hematopoietic cells with a stem cell stimulatory amount of INPROL and/or an opiate compound.| 83. A method as in claim 80 wherein said hematopoietic cells are cells selected from the group consisting of bone marrow cells, peripheral blood cells, mobilized peripheral blood cells, fetal liver and umbilical cord blood cells.| 84. A method as in claim 80 wherein said opiate compound is selected from the group of morphine, etorphine, codeine, heroin, hydromorphone, oxymorphone, levorphanol, levallorphan, codeine, hydrocodone, oxycodone, nalorphine, naloxone, naltrexone, buprenorphine, butanorphanol, nalbuphine, meperidine, alphaprodine, diphenoxylate, fentanyl, DAMGO, DALDA and nociceptin.| 85. A pharmaceutical composition comprising (a) an opiate compound and (b) at least one inhibitory compound selected from the group consisting of MIP-la, TGFj3, TNFa, INFa, INF(3, INFy, the pentapeptide pyroGlu-Glu-Asp-Cys-Lys, the tetrapeptide N-Acetyl-Ser-Asp-Lys-Pro, and the tripeptide glutathione (Gly-Cys-TGlu).| 124| 86. A pharmaceutical composition comprising (a) an opiate compound and (b) at least one stimulatory compound selected from the group consisting of IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-9, IL-11, IL-13, IL-14, IL-15, G-CSF, GM-CSF, M-CSF, erythropoietin, thrombopoietin, stem cell factor, and flk2/flt3 ligand.| 87. The use of INPROL in the manufacture of a medicament for use in a method of treating pain in a mammal,| 88. The use as in claim 87 wherein said INPROL is selected from the group the alpha chain of hemoglobin,the beta chain of hemoglobin,the gamma chain of hemoglobin, the delta chain of hemoglobin, the epsilon chain of hemoglobin, the zeta chain of hemoglobin,| a polypeptide having the sequence of amino acids 1-97 of the human alpha hemoglobin chain,| a polypeptide having the sequence of amino acids 1-94 of the human alpha hemoglobin chain,| Phe-Pro-His-Phe-Asp-Leu-Ser-His-Gly-Ser-Ala-Gln-Val, Cys-Phe-Pro-His-Phe-Asp-Leu-Ser-His-Gly-Ser-Ala-Gln-Val-Cys, and Asp-Ala-Leu-Thr-Asn-Ala-Val-Ala-His-Val-Asp-Asp-Met-Pro-Asn-Ala-Leu-Ser-Ala.| 89. The use of"INPROL in the manufacture of a medicament for use in a method of treating immune deficiency in a mammal.| 125| 88. The use as in claim 89 wherein said INPROL is selected from the group the alpha chain of hemoglobin,the beta chain of hemoglobin,the gamma chain of hemoglobin, the delta chain of hemoglobin, the epsilon chain of hemoglobin, the zeta chain of hemoglobin,| a polypeptide having the sequence of amino acids 1-97 of the human alpha hemoglobin chain,| a polypeptide having the sequence of amino acids 1-94 of the human alpha hemoglobin chain,| Phe-Pro-His-Phe-Asp-Leu-Ser-His-Gly-Ser-Ala-Gln-Val, Cys-Phe-Pro-His-Phe-Asp-Leu-Ser-His-Gly-Ser-Ala-Gln-Val-Cys, and Asp-Ala-Leu-Thr-Asn-Ala-Val-Ala-His-Val-Asp-Asp-Met-Pro-Asn-Ala-Leu-Ser-Ala.| 126| 89. A polypeptide of any one of claims 1 to 3 substantially as herein described with reference to the accompanying examples.| 90. A pharmaceutical composition comprising a polypeptide of claim 89 and a pharmaceutically acceptable carrier.| 91. The use of a polypeptide of either one of claims 1 or 2 in the manufacture of a preparation for use in a method of treating cancer which method comprises:| a) removing hematopoietic cells from said mammal,| b) treating said hematopoietic cells ex vivo with a preparation comprising a polypeptide as in claim| 1 or 2,| c) treating said hematopoietic cells of step b with chemotherapy or radiation,| d) performing myeloablative treatment on said mammal, and e) transplanting into said mammal the hematopoietic cells of step c.| 92. The use of a polypeptide of any one of claims 1 or 2 in the manufacture of a preparation for use in a method of maintaining mammalian hematopoietic skin cells ex vivo.| 93 . The use of a polypeptide of either one of claims 1 to 2 in the manufacture of preparation for use in a method of conducting gene therapy in a mammal which method comprises:| a) removing hematopoietic cells from said mammal,| b) transfecting said hematopoietic cells with a predetermined gene,| c) contacting said transfected hematopoietic cells ex vivo with a preparation comprising a polypeptide as in claim 1 or 2,| d) transplanting into said mammal the hematopoietic cells of sep c.| 94. The use of a polypeptide of either one of claims 1 or 2 in the manufacture of a preparation for use in a method of| 127| « •| 95. The use of INPROL and/or an opiate compound in the manufacture of a preparation for use in a method of stem cell proliferation.| 96. The use of a compound capable of binding opiate receptors in the manufacture of a preparation for use in a method of stimulating stem cell proliferation.| 97. The use of a compound capable of binding nociceptin receptors in the manufacture of a preparation for use in a method of stimulating or inhibiting stem cell proliferation.| 98. The use of a compound capable of activating the Ginhibitory subclass of GTP binding proteins in the manufacture of a preparation for use in a method of stimulating or inhibiting stem cell proliferation.| 99. The use of a compound capable of binding to an opiate-like receptor not including the classical mu, kappa or delta opiate receptors of 0RL1, wherein said receptor (a) has stem cell stimulating and/or inhibiting properties and (b) has said stem cell stimulating and/or inhibiting ability antagonizable by naloxone, in the manufacture of a preparation for use in a method of stimulating or inhibiting stem cell proliferation.| 100. The use of INPROL and or an opiate compound in the manufacture of a preparation for use in a method of maintaining mammalian hematopoietic stem cells ex vivo.| 101. The use of INPROL and/or an opiate compound in the manufacture of a preparation for use in a method of conducting gene therapy in a mammal which method comprises:| a) removing hematopoietic cells from said mammal,| b) treating said hematopoietic cells ex vivo with a stem cell stimulatory amount of INPROL and/or an opiate compound,| c) transfecting or infecting said hematopoietic cells with a predetermined gene,| d) contacting said transfected hematopoietic cells ex vivo with a stem cell inhibitory amount of INPROL and/or an opiate| «•| a predetermined gene,| d) contacting said transfected hematopoietic cells ex vivo with a stem cell inhibitory amount of INPROL and/or an opiate compound,| e) transplanting into said mammal the hematopoietic cells of step d,| f) optionally treating said mammal ex vivo with a stem cell inhibitory or stimulatory quantity INPROL and/or an opiate compound.| 102. The use of INPROL and/or an opiate compound in the manufacture of a preparation for use in a method for conducting ex vivo stem cell expansion.| 129|


申请人


发明人


优先权信息

  • US19970832443

申请人地址


代理人信息

  •  

IPC分类号


CPC分类号


USPC分类号