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1. 发明授权

US5986059A T-cell selective interleukin-4 agonists 失效
标题翻译： T细胞选择性白细胞介素-4激动剂
公开(公告)号：US5986059A
公开(公告)日：1999-11-16
申请号：US874697
申请日：1997-06-13
申请人： Armen B. Shanafelt , Jeffrey Greve , Robert Gundel
发明人： Armen B. Shanafelt , Jeffrey Greve , Robert Gundel
IPC分类号： A61K38/00 , C07K14/54 , C07K14/52 , A61K38/19
CPC分类号： C07K14/5406 , A61K38/00 , Y10S930/141
摘要： The invention is directed to human IL-4 muteins numbered in accordance with wild-type IL-4 having T cell activating activity, but having reduced endothelial cell activating activity. In particular, the invention is related to human IL-4 muteins wherein the surface-exposed residues of the D helix of the wild-type IL-4 are mutated whereby the resulting mutein causes T cell proliferation, and causes reduced IL-6 secretion from HUVECs, relative to wild-type IL-4. This invention realizes a less toxic IL-4 mutant that allows greater therapeutic use of this interleukin. Further, the invention is directed to IL-4 muteins having single, double and triple mutations represented by the designators R121A, R121D, R121E, R121F, R121H, R1211, R121K, R121N, R121P, R121T, R121W; Y124A, Y124Q, Y124R, Y124S, Y124T; Y124A/S125A, T13D/R121E; and R121T/E122F/Y124Q, when numbered in accordance with wild type IL-4 (His=1). The invention also includes polynucleotides coding for the muteins of the invention, vectors containing the polynucleotides, transformed host cells, pharmaceutical compositions comprising the muteins, and therapeutic methods of treatment.
摘要翻译：本发明涉及根据具有T细胞活化活性但具有降低的内皮细胞活化活性的野生型IL-4编号的人IL-4突变蛋白。特别地，本发明涉及人IL-4突变蛋白，其中暴露于野生型IL-4的D螺旋的表面暴露残基被突变，由此产生的突变蛋白导致T细胞增殖，并导致IL-6分泌降低 HUVECs相对于野生型IL-4。本发明实现了一种毒性较小的IL-4突变体，可以更好地治疗这种白介素。此外，本发明涉及具有由指示符R121A，R121D，R121E，R121F，R121H，R1211，R121K，R121N，R121P，R121T，R121W表示的单，双和三重突变的IL-4突变蛋白; Y124A，Y124Q，Y124R，Y124S，Y124T; Y124A / S125A，T13D / R121E; 和R121T / E122F / Y124Q，根据野生型IL-4（His = 1）编号。本发明还包括编码本发明的突变蛋白的多核苷酸，含有多核苷酸的载体，转化的宿主细胞，包含突变蛋白的药物组合物和治疗方法。

2. 发明授权

US06433157B1 Polynucleotides encoding T-cell selective interleukin-4 agonists 失效
标题翻译：编码T细胞选择性白细胞介素-4激动剂的多核苷酸
公开(公告)号：US06433157B1
公开(公告)日：2002-08-13
申请号：US09408629
申请日：1999-09-30
申请人： Armen B. Shanafelt , Jeffrey Greve , Robert Gundel
发明人： Armen B. Shanafelt , Jeffrey Greve , Robert Gundel
IPC分类号： C07H2104
CPC分类号： C07K14/5406 , A61K38/00 , Y02A50/401 , Y02A50/411 , Y10S930/141
摘要： The invention is directed to human IL-4 muteins numbered in accordance with wild-type IL-4 having T cell activating activity, but having reduced endothelial cell activating activity. In particular, the invention is related to human IL-4 muteins wherein the surface-exposed residues of the D helix of the wild-type IL-4 are mutated whereby the resulting mutein causes T cell proliferation, and causes reduced IL-6 secretion from HUVECs, relative to wild-type IL-4. This invention realizes a less toxic IL-4 mutant that allows greater therapeutic use of this interleukin. Further, the invention is directed to IL-4 muteins having single, double and triple mutations represented by the designators R121A, R121D, R121E, R121F, R121H, R121I, R121K, R121N, R121P, R121T, R121W; Y124A, Y124Q, Y124R, Y124S, Y124T; Y124A/S125A, T13D/R121E; and R121T/E122F/Y124Q, when numbered in accordance with wild type IL-4 (His=1). The invention also includes polynucleotides coding for the muteins of the invention, vectors containing the polynucleotides, transformed host cells, pharmaceutical compositions comprising the muteins, and therapeutic methods of treatment.
摘要翻译：本发明涉及根据具有T细胞活化活性但具有降低的内皮细胞活化活性的野生型IL-4编号的人IL-4突变蛋白。特别地，本发明涉及人IL-4突变蛋白，其中暴露于野生型IL-4的D螺旋的表面暴露残基被突变，由此产生的突变蛋白导致T细胞增殖，并导致IL-6分泌降低 HUVECs相对于野生型IL-4。本发明实现了一种毒性较小的IL-4突变体，可以更好地治疗这种白介素。此外，本发明涉及具有由指示符R121A，R121D，R121E，R121F，R121H，R121I，R121K，R121N，R121P，R121T，R121W表示的单，双和三重突变的IL-4突变蛋白; Y124A，Y124Q，Y124R，Y124S，Y124T; Y124A / S125A，T13D / R121E; 和R121T / E122F / Y124Q，根据野生型IL-4（His = 1）编号。本发明还包括编码本发明的突变蛋白的多核苷酸，含有多核苷酸的载体，转化的宿主细胞，包含突变蛋白的药物组合物和治疗方法。

3. 发明授权

US06335426B1 T-cell selective interleukin-4 agonists 失效
标题翻译： T细胞选择性白细胞介素-4激动剂
公开(公告)号：US06335426B1
公开(公告)日：2002-01-01
申请号：US09298374
申请日：1999-04-23
申请人： Armen B. Shanafelt , Jeffrey M. Greve , Robert Gundel
发明人： Armen B. Shanafelt , Jeffrey M. Greve , Robert Gundel
IPC分类号： C07K100
CPC分类号： C07K14/5406 , A61K38/00 , Y02A50/401 , Y02A50/411
摘要： This invention realizes a less toxic IL-4 mutant that allows greater therapeutic use of interleukin 4. Further, the invention is directed to IL-4 muteins having single and double mutations represented by the designators R121E and T13D/R121E, numbered in accordance with wild type IL-4 (His=1). The invention also includes polynucleotides coding for the muteins of the invention, vectors containing the polynucleotides, transformed host cells, pharmaceutical compositions comprising the muteins, and therapeutic methods of treatment.
摘要翻译：本发明实现了一种毒性较小的IL-4突变体，其允许白细胞介素4的更大治疗用途。此外，本发明涉及具有按照野生型编号的指示符R121E和T13D / R121E表示的单突变和双突变的IL-4突变蛋白类型IL-4（His = 1）。本发明还包括编码本发明的突变蛋白的多核苷酸，含有多核苷酸的载体，转化的宿主细胞，包含突变蛋白的药物组合物和治疗方法。

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