Development of novel immune therapy for melanoma by targeting tumor associated macrophages

• Project/Area Number: 16K10143
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: Tohoku University
• Principal Investigator: Fujimura Taku 東北大学, 大学病院, 講師 (50396496)
• Co-Investigator(Kenkyū-buntansha): 神林 由美 東北大学, 医学系研究科, 助教 (50755303)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 悪性黒色腫 / 免疫療法 / 腫瘍随伴性マクロファージ / 皮膚悪性腫瘍 / sCD163 / 免疫調整因子 / 免疫チェックポイント阻害薬 / 治療効果予測メカニズム / 治療 / 免疫関連副作用 / 腫瘍免疫 / 腫瘍随伴マクロファージ / ケモカイン / 抑制型免疫環境 / PD-1/ PD-L1

Outline of Final Research Achievements

We have developed several novel systems for tumor immunology fields, especially in the areas of tumor associated macrophages. During this period, we have published 15 research studies about tumor associated macrophages. Among them, we have determined safety dose of IFN-beta in combination with anti-PD1 antibodies, which is based on the logics of tumor associated macrophages. Moreover, we also found the release of sCD163 and CXCL5 from tumor associated macrophages, which could be the biomarker for the prediction of the efficacy of anti-PD1 antibodies for the treatment of advanced, unresectable melanoma patients. Furthermore, we found that these biomarkers are also useful for the prediction of immune related adverse events in patients with melanoma who treated with anti-PD1 antibodies. According to these results, today, we have set up a clinical research for the development of optimal immune therapy using anti-PD1 antibody.

Academic Significance and Societal Importance of the Research Achievements

当該研究により、ほとんど全ての皮膚悪性腫瘍において、CD163陽性腫瘍随伴性マクロファージが腫瘍間質に存在することが明らかとなった。さらに、悪性黒色腫においては、この腫瘍随伴性マクロファージ由来であるsCD163が健常人に比べて有意に上昇していること、悪性黒色腫においては抗PD1抗体の使用前後に変動し、この変動により抗PD1抗体の治療効果を予想できることが推測される基礎データを取ることができた。これらの基礎データをもとにして、臨床研究を行い、現在、国際特許１件と特願２件を確保した。今後、本データは免疫チェックポイント阻害薬の効果予測のバイオマーカーを決定するに当たり、重要なデータとなりうる。

Research Products

• [Journal Article] First-in-human clinical study of novel technique to diagnose malignant melanoma via thermal conductivity measurements (2019)
  • Author(s): Okabe T, Fujimura T, Okajima J, Kambayashi Y, Aiba S, Maruyama S.
  • Journal Title: Sci Rep Volume: 9 Issue: 1 Pages: 1-7
  • DOI: 10.1038/s41598-019-40444-6
  • Peer Reviewed / Open Access
• [Journal Article] BRAF kinase inhibitors for treatment of melanoma: developments from early-stage animal studies to Phase II clinical trials (2018)
  • Author(s): Fujimura T, Hidaka T, Kambayashi Y, Aiba S
  • Journal Title: Expert Opin Investig Drugs Volume: 28 Issue: 2 Pages: 143-148
  • DOI: 10.1080/13543784.2019.1558442
  • Peer Reviewed
• [Journal Article] Serum Level of Soluble CD163 May Be a Predictive Marker of the Effectiveness of Nivolumab in Patients With Advanced Cutaneous Melanoma (2018)
  • Author(s): Fujimura T, Sato Y, Tanita K, Kambayashi Y, Otsuka A, Fujisawa Y, Yoshino K, Matsushita S, Funakoshi T, Hata H, Yamamoto Y, Uchi H, Nonomura Y, Tanaka R, Aoki M, Imafuku K, Okuhira H, Wada N, Irie H, Hidaka T, Hashimoto A, Aiba S.
  • Journal Title: Front Oncol Volume: 19 Pages: 530-530
  • DOI: 10.3389/fonc.2018.00530
  • NAID: 120007133653
  • Peer Reviewed / Open Access
• [Journal Article] Minocycline decreases Th2 chemokines from M2 macrophages: Possible mechanisms for the suppression of bullous pemphigoid by traditional bullous disease drugs (2018)
  • Author(s): Tanita K, Fujimura T, Sato Y, Lyu C, Aiba S.
  • Journal Title: Exp Dermatol Volume: 27 Issue: 11 Pages: 1268-1272
  • DOI: 10.1111/exd.13779
  • Peer Reviewed
• [Journal Article] Three patients with advanced cutaneous angiosarcoma treated with eribulin: investigation of serum soluble CD163 and chemokine (C-X-C motif) ligand 10 as possible biomarkers predicting the biological behaviour of angiosarcoma (2018)
  • Author(s): Fujimura T, Sato Y, Kambayashi Y, Tanita K, Tsukada A, Terui H, Hashimoto A, Aiba S.
  • Journal Title: Br J Dermatol Volume: 6 Issue: 6 Pages: 1392-1395
  • DOI: 10.1111/bjd.16676
  • Peer Reviewed
• [Journal Article] Serum levels of soluble CD163 and CXCL5 may be predictive markers for immune-related adverse events in patients with advanced melanoma treated with nivolumab: a pilot study. (2018)
  • Author(s): Fujimura T, Sato Y, Tanita K, Kambayashi Y, Otsuka A, Fujisawa Y, Yoshino K, Matsushita S, Funakoshi T, Hata H, Yamamoto Y, Uchi H, Nonomura Y, Tanaka R, Aoki M, Imafuku K, Okuhira H, Furudate S, Hidaka T, Aiba S.
  • Journal Title: Oncotarget. Volume: 9 Issue: 21 Pages: 15542-15551
  • DOI: 10.18632/oncotarget.24509
  • Peer Reviewed / Open Access
• [Journal Article] Tumor-associated macrophages: Therapeutic targets for skin cancer. (2018)
  • Author(s): Fujimura T, Kambayashi Y, Fujisawa Y, Hidaka T, Aiba S.
  • Journal Title: Frontier in Oncology Volume: 8 Pages: 3-3
  • DOI: 10.3389/fonc.2018.00003
  • NAID: 120007134526
  • Peer Reviewed / Open Access
• [Journal Article] The Expression of Matrix Metalloproteinases in Receptor Activator of Nuclear Factor Kappa-B Ligand (RANKL)-expressing Cancer of Apocrine Origin. (2018)
  • Author(s): Kambayashi Y, Fujimura T, Furudate S, Lyu C, Hidaka T, Kakizaki A, Sato Y, Tanita K, Aiba S.
  • Journal Title: Anticancer Res. Volume: 38 Pages: 113-120
  • Peer Reviewed
• [Journal Article] Increased serum production of soluble CD163 and CXCL5 in patients with moyamoya disease: Involvement of intrinsic immune reaction in its pathogenesis (2018)
  • Author(s): Fujimura M, Fujimura T, Kakizaki A, Sato-Maeda M, Niizuma K, Tomata Y, Aiba S, Tominaga T
  • Journal Title: Brain Res Volume: 1679 Pages: 39-44
  • DOI: 10.1016/j.brainres.2017.11.013
  • Peer Reviewed
• [Journal Article] Two cases of Vogt-Koyanagi Harada disease-like uveitis developing from an advanced melanoma patient treated by sequential administration of nivolumab and dabrafenib/ trametinib therapy. (2018)
  • Author(s): Fujimura T, Kambayashi Y, Tanita K, Sato Y, Hidaka T, Otsuka A, Tanaka H, Furudate S, Hashimoto A, Aiba S.
  • Journal Title: Journal of Dermatology Volume: 印刷中 Issue: 6 Pages: 735-737
  • DOI: 10.1111/1346-8138.14273
  • Peer Reviewed
• [Journal Article] Successful Treatment of Nivolumab-Resistant Multiple In-Transit Melanomas with Ipilimumab and Topical Imiquimod. (2018)
  • Author(s): Fujimura T, Kambayashi Y, Sato Y, Tanita K, Furudate S, Tsukada A, Tono H, Hashimoto A, Aiba S.
  • Journal Title: Case Reports in Oncology Volume: 11 Issue: 1 Pages: 1-5
  • DOI: 10.1159/000485612
  • Peer Reviewed / Open Access
• [Journal Article] Successful Treatment of Erythrodermic Mycosis Fungoides with Mogamulizumab Followed by Etoposide Monotherapy. (2018)
  • Author(s): Fujimura T, Tanita K, Sato Y, Kambayashi Y, Furudate S, Tsukada A, Hashimoto A, Aiba S.
  • Journal Title: Case Reports in Oncology Volume: 11 Issue: 1 Pages: 29-32
  • DOI: 10.1159/000486278
  • Peer Reviewed / Open Access
• [Journal Article] Intensity-Modulated Radiotherapy Triggers Onset of Bullous Pemphigoid in a Patient with Advanced Melanoma Treated with Nivolumab. (2018)
  • Author(s): Tanita K, Fujimura T, Kambayashi Y, Tsukada A, Sato Y, Hashimoto A, Aiba S.
  • Journal Title: Case Reports in Oncology Volume: 11 Issue: 1 Pages: 114-118
  • DOI: 10.1159/000487127
  • Peer Reviewed / Open Access
• [Journal Article] The Expression of Matrix Metalloproteinases in Receptor Activator of Nuclear Factor Kappa-B Ligand (RANKL)-expressing Cancer of Apocrine Origin. (2018)
  • Author(s): Kambayashi Y, Fujimura T, Furudate S, Lyu C, Hidaka T, Kakizaki A, Sato Y, Tanita K, Aiba S.
  • Journal Title: Anticancer Reserch Volume: 38 Pages: 113-120
  • Peer Reviewed
• [Journal Article] Successful treatment of relapsed folliculotropic mycosis fungoides with mogamulizumab followed by intensity-modulated radiotherapy. (2018)
  • Author(s): Fujimura T, Furudate S, Tanita K, Sato Y, Kambayashi Y, Hidaka T, Aiba S.
  • Journal Title: Journal of Dermatology Volume: 印刷中 Issue: 4
  • DOI: 10.1111/1346-8138.14111
  • Peer Reviewed
• [Journal Article] Severe erythema exudative multiforme developing from advanced melanoma treated with dabrafenib and trametinib followed by nivolumab. (2018)
  • Author(s): Fujimura T, Kambayashi Y, Hidaka T, Tamabuchi E, Otake E, Tono H, Mizuashi M, Furudate S, Aiba S.
  • Journal Title: Journal of Dermatology Volume: 45 Issue: 2
  • DOI: 10.1111/1346-8138.14085
  • Peer Reviewed
• [Journal Article] Successful control of phototherapy-resistant lymphomatoid papulosis with oral bexarotene. (2018)
  • Author(s): Fujimura T, Furudate S, Tanita K, Sato Y, Kambayashi Y, Hidaka T, Aiba S.
  • Journal Title: Journal of Dermatology Volume: 45 Issue: 2
  • DOI: 10.1111/1346-8138.14095
  • Peer Reviewed
• [Journal Article] Cytotoxic antimelanoma drugs suppress the activation of M2 macrophages. (2018)
  • Author(s): Fujimura T, Kakizaki A, Kambayashi Y, Sato Y, Tanita K, Lyu C, Furudate S, Aiba S.
  • Journal Title: Experimental Dermatology Volume: 27 Issue: 1 Pages: 64-70
  • DOI: 10.1111/exd.13417
  • Peer Reviewed / Open Access
• [Journal Article] Phase I study of nivolumab combined with IFN-b for patients with advanced melanoma. (2017)
  • Author(s): Fujimura T, Hidaka T, Kambayashi Y, Furudate S, Kakizaki A, Tono H, Tsukada A, Haga T, Hashimoto A, Morimoto R, Yamaguchi T, Takano T, Aiba S.
  • Journal Title: Oncotarget Volume: 8 Issue: 41 Pages: 71177-71181
  • DOI: 10.18632/oncotarget.17090
  • Peer Reviewed / Open Access
• [Journal Article] Immunomodulatory Effect of Imiquimod Through CCL22 Produced by Tumor-associated Macrophages in B16F10 Melanomas. (2017)
  • Author(s): Furudate S, Fujimura T, Kambayashi Y, Kakizaki A, Hidaka T, Aiba S.
  • Journal Title: Anticancer Research Volume: 37 Pages: 3461-3471
  • Peer Reviewed
• [Journal Article] The Immunological Roles of Periostin/Tumor-Associated Macrophage Axis in Development of Dermatofibrosarcoma Protuberans. (2017)
  • Author(s): Fujimura T, Kakizaki A, Sato Y, Tanita K, Furudate S, Aiba S.
  • Journal Title: Anticancer Research Volume: 37 Pages: 2867-2873
  • Peer Reviewed
• [Journal Article] Phospho-STAT5B Expression Is a Prognostic Marker for Merkel Cell Carcinoma. (2017)
  • Author(s): Fujimura T, Furudate S, Kambayahsi Y, Kakizaki A, Yamamoto Y, Okuhira H, Fujimoto N, Aiba S.
  • Journal Title: Anticancer Research Volume: 37 Pages: 2335-2341
  • Peer Reviewed
• [Journal Article] Keratoacanthoma, palmoplantar keratoderma developing in an advanced melanoma patient treated with vemurafenib regressed by blockade of mitogen-activated protein kinase kinase signaling. (2017)
  • Author(s): Furudate S, Fujimura T, Kambayashi Y, Hidaka T, Sato Y, Tanita K, Hashimoto A, Aiba S.
  • Journal Title: Journal of Dermatology Volume: 46 Issue: 9
  • DOI: 10.1111/1346-8138.13898
  • Peer Reviewed
• [Journal Article] Retrospective Investigation of Cutaneous Squamous Cell Carcinoma on the Lip Treated with Peplomycin Administered Through a Superficial Temporal Artery. (2017)
  • Author(s): Fujimura T, Takahashi K, Kambayashi Y, Furudate S, Hidaka T, Kakizaki A, Watabe A, Haga T, Hashimoto A, Aiba S.
  • Journal Title: Anticancer Research Volume: 37 Pages: 1885-1889
  • Peer Reviewed
• [Journal Article] Phospho-STAT5B expression is a prognostic marker for Merkel cell carcinoma. (2017)
  • Author(s): Fujimura T, Furudate S, Kambayashi Y, Kakizaki A, Yamamoto Y, Okuhira H, Fujimoto N, Aiba S.
  • Journal Title: Anticancer Research Volume: 1 Pages: 1-1
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Keratoacanthoma, palmoplantar keratoderma developing from an advanced melanoma patient treated with vemurafenib regressed by the blockade of MEK signaling. (2017)
  • Author(s): 3.Furudate S, Fujimura T, Kambayashi Y, Hidaka T, Sato Y, Tanita K, Hashimoto A, Aiba S
  • Journal Title: Journal of Dermatology Volume: 1 Pages: 1-1
  • Peer Reviewed
• [Journal Article] Phase I study of nivolumab combined with IFN-β for patients with advanced melanoma. (2017)
  • Author(s): Fujimura T, Hidaka T, Kambayashi Y, Furudate S, Kakizaki A, Tono H, Tsukada A, Haga T, Hashimoto A, Morimoto R, Yamaguchi T, Takano T, Aiba S.
  • Journal Title: Oncotarget Volume: 1 Pages: 1-1
  • Peer Reviewed / Open Access
• [Journal Article] Retrospective study of cutaneous squamous cell carcinoma on the lip treated with peplomycin administered through a superficial temporal artery. (2017)
  • Author(s): Fujimura T, Takahashi K, Kambayashi Y, Furudate S, Hidaka T, Kakizaki A, Watabe A, Haga T, Hashimoto A, Aiba S.
  • Journal Title: Anticancer Research Volume: 1 Pages: 1-1
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] The aryl hydrocarbon receptor AhR links atopic dermatitis and air pollution via induction of the neurotrophic factor artemin. (2017)
  • Author(s): Hidaka, T., Ogawa, E., Kobayashi, E.H., Suzuki, T., Funayama, R., Nagashima, T., Fujimura, T., Aiba, S., Nakayama, K., Okuyama, R., Yamamoto, M.
  • Journal Title: Nat. Immunol. Volume: 18 Issue: 1 Pages: 64-73
  • DOI: 10.1038/ni.3614
  • Peer Reviewed
• [Journal Article] Possible mechanisms of the crosstalk between Langerhans cells and regulatory T cells in extramammary Paget’s disease by receptor activator of nuclear factor kappa-B ligand (RANKL)/ RANK pathways. (2017)
  • Author(s): Fujimura T, Kambayashi Y, Furudate S, Kakizaki A, Takanori Hidaka, Setsuya Aiba.
  • Journal Title: British Journal of Dermatology Volume: 176 Issue: 2 Pages: 387-394
  • DOI: 10.1111/bjd.14864
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Peripheral blood Th9 cells are a possible pharmacodynamic biomarker of nivolumab treatment efficacy in metastatic melanoma patients. (2016)
  • Author(s): Nonomura Y, Otsuka A, Nakashima C, Seidel JA, Kitoh A, Dainichi T, Nakajima S, Sawada Y, Matsushita S, Aoki M, Takenouchi T, Fujimura T, Hatta N, Koreeda S, Fukushima S, Honda T, Kabashima K.
  • Journal Title: Oncoimmunology Volume: 5(12) Issue: 12 Pages: e1248327-e1248327
  • DOI: 10.1080/2162402x.2016.1248327
  • Peer Reviewed
• [Journal Article] Tumor-associated macrophages in skin: how to treat their heterogeneity and plasticity. (2016)
  • Author(s): Fujimura T, Kakizaki A, Furudate S, Kambayashi Y, Aiba S.
  • Journal Title: Journal of Dermatological Science Volume: 83 Issue: 3 Pages: 167-173
  • DOI: 10.1016/j.jdermsci.2016.05.015
  • Peer Reviewed
• [Journal Article] Tumor-associated M2 macrophages in mycosis fungoides aquired immunomodulatory function by interferon alpha and interferon gamma. (2016)
  • Author(s): Furudate S, Fujimura T, Kakizaki A, Hidaka T, Asano M, Aiba S.
  • Journal Title: Journal of Dermatological Science Volume: 83 Issue: 3 Pages: 182-189
  • DOI: 10.1016/j.jdermsci.2016.05.004
  • Peer Reviewed
• [Presentation] 皮膚T細胞リンパ腫の治療: 免疫背景から考えるベキサロテンの役割 (2018)
  • Author(s): 藤村卓
  • Organizer: 第82回日本皮膚科学会東京支部会
  • Invited
• [Presentation] 皮膚T細胞性リンパ腫治療におけるベキサロテンの役割 (2018)
  • Author(s): 藤村卓
  • Organizer: 第70回日本皮膚科学会西部支部会
  • Invited
• [Presentation] 15.The efficacy of eribulin methylate for patients with paclitaxel-resistant cutaneous angiosarcoma: interim result of multi-center, prospective observational study. (2018)
  • Author(s): Fujisawa Y, Yoshino K, Fujimura T, （他１２名）
  • Organizer: ESMO 2018 Congress
  • Int'l Joint Research
• [Presentation] エリブリン・メシル酸塩を使用したタキサン系抗癌剤抵抗性皮膚血管肉腫の３例 (2018)
  • Author(s): 藤村卓（他６名）
  • Organizer: 第82回日本皮膚科学会東部支部学術大会
• [Presentation] 進化し続ける悪性黒色腫の治療：理想的免疫療法をめざして (2018)
  • Author(s): 藤村卓
  • Organizer: 第34回日本皮膚悪性腫瘍学会総会
  • Invited
• [Presentation] 免疫チェックポイント阻害薬による免疫関連副作用の予測システムの開発 (2018)
  • Author(s): 藤村卓（他９名）
  • Organizer: 第117回日本皮膚科学会総会
• [Presentation] 非侵襲熱物性計測による皮膚腫瘍の早期診断手法の開発 (2018)
  • Author(s): 佐藤遥太、藤村卓（他５名）
  • Organizer: 第117回日本皮膚科学会総会
• [Presentation] 進化する悪性黒色腫治療：複合免疫療法の可能性 (2018)
  • Author(s): 藤村卓
  • Organizer: 第34回臨床皮膚科学会総会
  • Invited
• [Presentation] Safety dose and prediction of immune-related adverse event of nivolumab combined with IFN-beta in patients with advanced melanoma (2017)
  • Author(s): Taku Fujimura, Yumi Kambayashi, Sadanori Furudate, Takanori Hidaka, Hisayuki Tono, Yota Sato, Kayo Tanita, Akira Hashimoto, Setsuya Aiba
  • Organizer: European Society for Dermatological Research 47th annual meeting
  • Int'l Joint Research
• [Presentation] Phase I study of the nivolumab combined with IFN-beta in patients with advanced melanoma (2017)
  • Author(s): Taku Fujimura, Yumi Kambayashi, Sadanori Furudate, Takanori Hidaka, Hisayuki Tono, Akira Tsukada, Akira Hashimoto, Setsuya Aiba
  • Organizer: Society for Investigative Dermatology 76 th annual meeting
  • Int'l Joint Research
• [Presentation] IL-36γ stimulates tumor-associated macrophages to recruit IL-17 producing cells in cutaneous squamous cell carcinoma (2017)
  • Author(s): Yota Sato, Taku Fujimura, Kayo Tanita, Lyu Chunbing, Takeshi Yamauchi, Setsuya Aiba
  • Organizer: Society for Investigative Dermatology 76 th annual meeting
  • Int'l Joint Research
• [Presentation] Bexarotene modulates the production of CCL22 from tumor-associated macrophages in patients with mycosis fungoides. (2017)
  • Author(s): Kayo Tanita, Taku Fujimura, Yota Sato, Lyu Chunbing, Yumi Kambayashi, Sadanori Furudate, Setsuya Aiba
  • Organizer: Japanese Society for Investigative Dermatology 42th annual meeting
  • Int'l Joint Research
• [Presentation] Tumor-associated macrophages recruit IL-17 producing cells to promote development of cutaneous squamous cell carcinoma. (2017)
  • Author(s): Yota Sato, Taku Fujimura, Kayo Tanita, Lyu Chunbing, Takeshi Yamauchi, Setsuya Aiba
  • Organizer: Japanese Society for Investigative Dermatology 42th annual meeting
  • Int'l Joint Research
• [Presentation] Tumor-associated macrophages in skin: how to treat their heterogeneity and plasticity (2016)
  • Author(s): Taku Fujimura
  • Organizer: Annual meeting of Japanese Society for Investigative Dermatology
  • Place of Presentation: 仙台、仙台国際センター
  • Year and Date: 2016-12-09
  • Int'l Joint Research / Invited
• [Presentation] A possible interaction between periostin and CD163+ skin-resident macrophages in pemphigus vulgaris and bullous pemphigoid. (2016)
  • Author(s): Taku Fujimura, Aya Kakizaki, Sadanori Furudate, Setsuya Aiba
  • Organizer: Annual meeting of European Society for Dermatological Research
  • Place of Presentation: ミュンヘン、ドイツ
  • Year and Date: 2016-09-07
  • Int'l Joint Research
• [Presentation] 悪性黒色腫治療戦略：更なる発展のために (2016)
  • Author(s): 藤村 卓
  • Organizer: 第32回日本皮膚悪性腫瘍学会
  • Place of Presentation: 鹿児島、かごしま県民交流センター
  • Year and Date: 2016-05-27
  • Invited
• [Patent(Industrial Property Rights)] 特願 (2018)
  • Inventor(s): 藤村卓
  • Industrial Property Rights Holder: 藤村卓
  • Industrial Property Rights Type: 特許
  • Filing Date: 2018
• [Patent(Industrial Property Rights)] 米国特許 (2017)
  • Inventor(s): 藤村卓
  • Industrial Property Rights Holder: 藤村卓
  • Industrial Property Rights Type: 特許
  • Filing Date: 2017
  • Acquisition Date: 2019
  • Overseas
• [Patent(Industrial Property Rights)] 免疫チェックポイント阻害薬使用における免疫関連副作用の予測方法 (2017)
  • Inventor(s): Taku Fujimura
  • Industrial Property Rights Holder: Taku Fujimura
  • Industrial Property Rights Type: 特許
  • Filing Date: 2017
  • Overseas
• [Patent(Industrial Property Rights)] 体外診断薬 (2016)
  • Inventor(s): 藤村 卓
  • Industrial Property Rights Holder: 藤村 卓
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2016-131913
  • Filing Date: 2016-07-01