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CELL MIGRATION MODULATOR

Foreign code F130007171
File No. S2012-0845-N0
Posted date Feb 25, 2013
Country WIPO
International application number 2011JP079263
International publication number WO 2012081711
Date of international filing Dec 12, 2011
Date of international publication Jun 21, 2012
Priority data
  • P2010-276777 (Dec 13, 2010) JP
Title CELL MIGRATION MODULATOR
Abstract Provided are: a cell migration modulator, a cell migration modulation method, a medical composition containing the modulator, and the like, which make possible the promotion and suppression of cell migration. This cell migration modulator is characterized in comprising the entire length of blood coagulation factor IX, a portion where the trypsin domain has been removed from the entire length of blood coagulation factor IX, a light chain of blood coagulation factor IX, or a peptide, derivative thereof, or salt thereof, the peptide including the EGF1 domain of blood coagulation factor IX or the EGF3 domain of endothelial cell locus-1 protein.
Outline of related art and contending technology BACKGROUND ART
9 Hemostatic clotting factors that are involved in the coagulation of the long-known (F9) is an essential and blood coagulation factors, protein known as the cause of hemophilia. F9 Is, in the course of the coagulation reaction (F11) coagulation factor 11 by the two fragments of the 2 (heavy chain, light chain) or the like can be cleaved by activated, to promote the coagulation reaction. F9 In, coagulation factor has a function as a critical part is the C-terminal side of the trypsin domain (heavy chain) and, the function of the N-terminal side (light chain) is not well known. Thrombus caused by blood coagulation, comprising a coagulation factor composed of a variety of proteins. Up to now, is easily formed within the thrombus or blood vessels, thrombus formation rate found in cancer patients confirmed that cancer metastasis is high (for example, non-patent document 1;Gerotziafas GT et al., see Thromb.,2008,vol.36(3-4), p.204-11 Clinical studies with anticoagulants to improve survival in cancer patients.Pathophysiol Haemost.), The mechanism and the main molecule has still not constant inconclusive. The relationship between the cancer metastasis and the thrombus was demonstrated by statistically, cancer metastasis by administering an anticoagulant to prevent the been made an attempt, a significant inhibition of cancer metastasis was confirmed. However, the use of anti-coagulant because it involves the risk of bleeding, there is a limit to the amount used. In addition, experience has shown that the methods are effective, mechanism is unknown, and widely have not yet been accomplished. However, cell migration, phenomenon which is essential in the life activities of the human body, human body involved in a wide range of phenomenon occurs but, at the same time, metastasis may cause undesirable results are known. In addition, other receptors involved in cell migration phenomenon may be, or angiogenesis, wound healing and the like are known.
In such a situation, enhancement or inhibition of cell migration can be performed with a cell migration-modulating agents, a method of controlling cell migration, and a pharmaceutical composition comprising the modulating agent has been desired development of. The present invention is, in consideration of the above circumstances with an object, shown below, cell migration modulating agent (for example, cell migration promoting agents, cell migration inhibitor), a method of controlling cell migration (for example, promoting cell migration, cell migration inhibition method), a pharmaceutical composition comprising the modifier (angiogenesis-promoting, wound or ulcer for, a cancer metastasis suppressing or inhibitory, or angiogenesis inhibitor or a pharmaceutical composition for the inhibition), as well as, for promoting the expansion of the cells, epithelial-like sequence of the cell holding method, developed The composition of cells, and cells of epithelial-like sequence composition and the like for holding system according to the invention. (1) 9 The entire length of the blood clotting factors, blood clotting factors of the total length of the portion except for the 9 trypsin domain, light chain 9 of the blood clotting factors, blood clotting factors 9 or EGF1 domain, EGF3 domain of the protein or endothelial cells a peptide containing the -1 locus, its derivatives or salts thereof and, cell migration-modulating agents. (2) (A) or (b) the following peptide, its derivatives or salts thereof and, cell migration-modulating agents. (a) Shown in SEQ ID NO:2, 4, 6, 8 or 12 comprising an amino acid sequence. (b) Amino acid sequence shown in SEQ ID NO:2, 4, 6, 8 or 12 in 1 or an amino acid deletion, substitution or addition of the amino acid sequence, and, a peptide having the cell migration activity. (3) (A) or (b) the following peptide, its derivatives or salts thereof and, cell migration promoting agent. (a) SEQ ID NO:6, or 8 comprising an amino acid sequence shown in 12. (b) SEQ ID NO:6, 1 or 8 the amino acid sequence shown in 12 or an amino acid deletion, substitution or addition of the amino acid sequence, and, a peptide having the activity to promote cell migration. (4) (A) or (b) the following peptide, its derivatives or salts thereof characterized in that, the cell migration inhibitor. (a) SEQ ID NO:2, 4, 8 or comprising an amino acid sequence shown in 12. (b) Amino acid sequence shown in SEQ ID NO:2, 4, 8 or 12 in 1 or an amino acid deletion, substitution or addition of the amino acid sequence, and, a peptide having cell migration inhibitory activity. (5) Animals of claims 1 or 2 and adjusted to be administered, method for the regulation of cell migration. (6) Promoter according to claim 3 animals and administering, promoting cell migration. (7) Inhibitor according to claim 4 animals characterized by administering, method of inhibiting cell migration. (8) Modifier of claims 1 or 2, the pharmaceutical composition. (9) Of an accelerator according to claim 3, pro-angiogenic pharmaceutical composition. (10) Of an accelerator according to claim 3, a pharmaceutical composition for wound or ulcer. (11) An inhibitor of according to claim 4, a pharmaceutical composition for inhibiting or blocking cancer metastasis. (12) An inhibitor of according to claim 4, a pharmaceutical composition for inhibiting or blocking angiogenesis. (13) Of the accelerating agents according to claim 3 characterized in that, for promoting the expansion of the cells. (14) According to claim 4 and inhibitors of, epithelial-like sequence of the cell holding method. And (14) in the methods of the above (13), cells include, for example and the cultured cells. (15) Of an accelerator according to claim 3, deployment of cells The composition. (16) Of an inhibitor according to claim 4, epithelial-like sequence composition for holding cells. And (16) in the compositions of the above (15), cells include, for example and the cultured cells. According to the present invention, enhancement or inhibition of cell migration cell migration-modulating agents can be performed, for example, to stimulate or inhibit the cell migration agent can be provided. Of the present invention cell migration-modulating agents include, for example, promoting angiogenesis, wound or ulcer treatment, inhibits or prevents cancer metastasis, or inhibit angiogenesis or inhibit be used in a pharmaceutical composition, and medical and pharmaceutical field of, is extremely useful. In addition, cell migration-modulating agents are of the present invention, by the promotion of cell migration to facilitate spreading of the cells (particularly the cells in culture) or, by the inhibition of cell migration of epithelial cells (particularly the cells in culture) of a target-like sequence may be used to hold is also effective.
Scope of claims (In Japanese)請求の範囲 [請求項1]
血液凝固第9因子の全長、血液凝固第9因子の全長からトリプシンドメインを除いた部分、血液凝固第9因子の軽鎖、若しくは血液凝固第9因子のEGF1ドメイン、又は内皮細胞遺伝子座-1タンパク質のEGF3ドメインを含むペプチド、その誘導体あるいはこれらの塩を含むことを特徴とする、細胞遊走調節剤。

[請求項2]
以下の(a)又は(b)のペプチド、その誘導体あるいはこれらの塩を含むことを特徴とする、細胞遊走調節剤。
 (a)配列番号2、4、6、8若しくは12に示されるアミノ酸配列を含むペプチド。
 (b)配列番号2、4、6、8若しくは12に示されるアミノ酸配列において1若しくは数個のアミノ酸が欠失、置換若しくは付加されたアミノ酸配列を含み、かつ、細胞遊走調節活性を有するペプチド。

[請求項3]
以下の(a)又は(b)のペプチド、その誘導体あるいはこれらの塩を含むことを特徴とする、細胞遊走促進剤。
 (a)配列番号6、8若しくは12に示されるアミノ酸配列を含むペプチド。
 (b)配列番号6、8若しくは12に示されるアミノ酸配列において1若しくは数個のアミノ酸が欠失、置換若しくは付加されたアミノ酸配列を含み、かつ、細胞遊走促進活性を有するペプチド。

[請求項4]
以下の(a)又は(b)のペプチド、その誘導体あるいはこれらの塩を含むことを特徴とする、細胞遊走抑制剤。
 (a)配列番号2、4、8若しくは12に示されるアミノ酸配列を含むペプチド。
 (b)配列番号2、4、8若しくは12に示されるアミノ酸配列において1若しくは数個のアミノ酸が欠失、置換若しくは付加されたアミノ酸配列を含み、かつ、細胞遊走抑制活性を有するペプチド。

[請求項5]
被験動物に請求項1又は2記載の調節剤を投与することを特徴とする、細胞遊走調節方法。

[請求項6]
被験動物に請求項3記載の促進剤を投与することを特徴とする、細胞遊走促進方法。

[請求項7]
被験動物に請求項4記載の抑制剤を投与することを特徴とする、細胞遊走抑制方法。

[請求項8]
請求項1又は2記載の調節剤を含む、医薬組成物。

[請求項9]
請求項3記載の促進剤を含む、血管新生促進用医薬組成物。

[請求項10]
請求項3記載の促進剤を含む、創傷又は潰瘍治療用医薬組成物。

[請求項11]
請求項4記載の抑制剤を含む、癌転移抑制又は阻害用医薬組成物。

[請求項12]
請求項4記載の抑制剤を含む、血管新生抑制又は阻害用医薬組成物。

[請求項13]
請求項3記載の促進剤を用いることを特徴とする、細胞の展開促進方法。

[請求項14]
請求項4記載の抑制剤を用いることを特徴とする、細胞の上皮様配列保持方法。

[請求項15]
細胞が培養細胞である、請求項13又は14記載の方法。

[請求項16]
請求項3記載の促進剤を含む、細胞の展開促進用組成物。

[請求項17]
請求項4記載の抑制剤を含む、細胞の上皮様配列保持用組成物。

[請求項18]
細胞が培養細胞である、請求項16又は17記載の組成物。

  • Applicant
  • ※All designated countries except for US in the data before July 2012
  • NIHON UNIVERSITY
  • Inventor
  • HIDAI, Chiaki
  • KITANO, Hisataka
  • MAMIYA, Atsushi
IPC(International Patent Classification)
Specified countries National States: AE AG AL AM AO AT AU AZ BA BB BG BH BR BW BY BZ CA CH CL CN CO CR CU CZ DE DK DM DO DZ EC EE EG ES FI GB GD GE GH GM GT HN HR HU ID IL IN IS KE KG KM KN KP KR KZ LA LC LK LR LS LT LU LY MA MD ME MG MK MN MW MX MY MZ NA NG NI NO NZ OM PE PG PH PL PT QA RO RS RU RW SC SD SE SG SK SL SM ST SV SY TH TJ TM TN TR TT TZ UA UG US UZ VC VN ZA ZM ZW
ARIPO: BW GH GM KE LR LS MW MZ NA RW SD SL SZ TZ UG ZM ZW
EAPO: AM AZ BY KG KZ MD RU TJ TM
EPO: AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR
OAPI: BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG
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