JP6004494B2 - デュピュイトラン病の治療 - Google Patents
デュピュイトラン病の治療 Download PDFInfo
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- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
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- C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
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- C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
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Description
また、上述する局所用製剤及び組合せも含まれる。
100人を超えるデュピュイトラン病患者の試料を収集して、筋線維芽細胞分布について検討した。100人を超えるデュピュイトラン病患者の筋に関する本発明者らのデータは、大多数の患者において、筋線維芽細胞が、患部の関節レベルで、手掌に位置する結節に集中することを示す(図1を参照)。図1によれば、筋線維芽細胞に多く存在する結節は、指関節の近傍に位置する。図1は次のことを示す。A:デュピュイトラン病患者の筋の手術時の観察。印をつけたのは、近位指節間関節(PIPJ; 1)の位置である。B:平滑筋アクチンが染色された組織切片の低倍率の顕微鏡写真。結節におけるα‐SMAを多く含む細胞の集合は、PIPJの近傍に位置する。C:α‐SMA陽性細胞(筋線維芽細胞)を示す、結節部位の高倍率写真。
次いで、結節を、他の細胞型、具体的には炎症細胞の存在において検討した。マクロファージ及びマスト細胞の多くが共に、筋の結節のない部位ではなく、結節に含まれることが分かった。
デュピュイトラン病患者の組織、及び手掌皮膚と非手掌皮膚の両方でRAGEの分布について検討した。本発明者らは、デュピュイトラン病患者の結節中のRAGEに対する多くの染色を発見し、これは、筋線維芽細胞と共に局在化していた(図8を参照)。指の筋の試料を縦方向に二分し、ホルマリンに固定した。組織切片を筋切断面から採取し、連続切片を、(A、C)α‐SMA及び(B、D)RAGE抗体について染色した。スケールバーを示す。像は、15の患者試料のものを表す。RAGEは、デュピュイトラン病患者の結節のα‐SMA分布と共に局在化する。
手掌線維芽細胞への外因性HMGB1の添加の影響について検討した。手掌線維芽細胞に接種したコラーゲンゲルを、TNF‐α(1 ng/ml)若しくはHMGB1(1 ng/ml)若しくはTGF‐β1(10 ng/ml)の存在下、又はこれがない状態(PS単独)で、24時間培養し、また、(Verjee et al, Hand Surg Am, 34, 1785-1794, 2009、及びVerjee et al, J Cell Physiol, 2010に記載されているような培養力モニター技術を利用して)等尺性の力収縮を定量した。試験データを、3回の試験(2回のHMGB1以外)の+/−SDとして図12に示す。
デュピュイトラン病患者の結節(筋線維芽細胞を含む)由来の初代継代培養細胞を、上述の培養力モニターを使用して、10 μg/mlの量で、モノクローナルヒトTNF‐α抗体(モノクローナルIGG1培養物#1825、R&Dシステムズ社(R&D Systems)(カナダ)から入手可能)によって処理した。かかる初代継代細胞の対照培養物と比較して、抗TNF‐α処理細胞は、30%以上の量の対照によって、24時間にわたり収縮することが分かった(対照と比較して、30%を超える効果的な筋線維芽細胞失活に相当すると考えられる。)。このことを図13に示し、24時間にわたる勾配(又は収縮の割合;ダイン/時間)を、対照細胞及びTNF‐α抗体処理細胞のそれぞれについて示す。
Claims (17)
- TNF-αアンタゴニストを含む、初期病状のデュピュイトラン病の処置用医薬組成物であって、前記初期病状とは、患者の手掌及び/又は指に結節が存在し、指の拘縮が20°未満である段階をいう、医薬組成物。
- TNF-αアンタゴニストが、抗TNF抗体若しくはその機能性断片、抗TNF抗体の機能性断片を含む融合タンパク質、TNF受容体若しくはTNF受容体の融合タンパク質、又は可溶性TNFαアンタゴニストである、請求項1記載の医薬組成物。
- TNF-αアンタゴニストが、抗TNF抗体又はその機能性断片である、請求項1又は2記載の医薬組成物。
- 抗TNF抗体又はその機能性断片が、ヒトモノクローナル抗体、組換えヒトモノクローナル抗体、完全ヒトモノクローナル抗体、又はヒト化抗体断片である、請求項3記載の医薬組成物。
- 抗TNF抗体又はその機能性断片が、完全ヒトモノクローナル抗体又はその機能性断片である、請求項3記載の医薬組成物。
- TNF-αアンタゴニストは、疾患部位又はその症状が発現している部位に局所投与される請求項1〜5のいずれか1項に記載の医薬組成物。
- TNF-αアンタゴニストは、患者の手の中の患部組織に直接注射される請求項1〜6のいずれか1項に記載の医薬組成物。
- TNF-αアンタゴニストは、患者の手の中の臨床的な結節中に注射により投与される請求項7記載の医薬組成物。
- TNF-αアンタゴニストは、マトリックスメタロプロテイナーゼ及び/又はコラゲナーゼを用いる補助的及び/又は併用処置と共に、主たる処置として投与される請求項1〜8記載の医薬組成物。
- TNF-αアンタゴニストと、マトリックスメタロプロテイナーゼ及び/又はコラゲナーゼとを含む請求項9記載の医薬組成物。
- TNF-αアンタゴニストが、インフリキシマブ、アダリムマブ、セルトリズマブペゴール、ゴリムマブ及びエタネルセプトから選ばれる1又は複数である請求項1〜10のいずれか1項に記載の医薬組成物。
- TNF-αアンタゴニストの、初期病状のデュピュイトラン病の処置用医薬の製造のための使用であって、前記初期病状とは、患者の手掌及び/又は指に結節が存在し、指の拘縮が20°未満である段階をいう、使用。
- TNF-αアンタゴニストが、抗TNF抗体若しくはその機能性断片、抗TNF抗体の機能性断片を含む融合タンパク質、TNF受容体若しくはTNF受容体の融合タンパク質、又は可溶性TNF-αアンタゴニストである、請求項12記載の使用。
- TNF-αアンタゴニストが、抗TNF抗体若しくはその機能性断片である、請求項12又は13記載の使用。
- 抗TNF抗体又はその機能性断片が、ヒトモノクローナル抗体、組換えヒトモノクローナル抗体、完全ヒトモノクローナル抗体、又はヒト化抗体断片である、請求項14記載の使用。
- 抗TNF抗体又はその機能性断片が、完全ヒトモノクローナル抗体又はその機能性断片である、請求項14記載の使用。
- TNF-αアンタゴニストが、インフリキシマブ、アダリムマブ、セルトリズマブペゴール、ゴリムマブ及びエタネルセプトから選ばれる1種である請求項12〜16のいずれか1項に記載の使用。
Applications Claiming Priority (7)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GBGB1018325.9A GB201018325D0 (en) | 2010-10-30 | 2010-10-30 | Treatment for dupuytren's disease |
GB1018325.9 | 2010-10-30 | ||
GB1018362.2 | 2010-11-01 | ||
GBGB1018362.2A GB201018362D0 (en) | 2010-11-01 | 2010-11-01 | Treatment of dupuytren's disease |
GBGB1113718.9A GB201113718D0 (en) | 2011-08-10 | 2011-08-10 | Treatment of Dupuytren's Disease |
GB1113718.9 | 2011-08-10 | ||
PCT/EP2011/069147 WO2012056044A1 (en) | 2010-10-30 | 2011-10-31 | Treatment for dupuytren's disease |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
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JP2016166524A Division JP2017014266A (ja) | 2010-10-30 | 2016-08-29 | デュピュイトラン病の治療 |
Publications (3)
Publication Number | Publication Date |
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JP2013540803A JP2013540803A (ja) | 2013-11-07 |
JP2013540803A5 JP2013540803A5 (ja) | 2014-12-18 |
JP6004494B2 true JP6004494B2 (ja) | 2016-10-12 |
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JP2013535462A Active JP6004494B2 (ja) | 2010-10-30 | 2011-10-31 | デュピュイトラン病の治療 |
JP2016166524A Pending JP2017014266A (ja) | 2010-10-30 | 2016-08-29 | デュピュイトラン病の治療 |
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JP2016166524A Pending JP2017014266A (ja) | 2010-10-30 | 2016-08-29 | デュピュイトラン病の治療 |
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Country | Link |
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US (3) | US9138458B2 (ja) |
EP (1) | EP2632446B1 (ja) |
JP (2) | JP6004494B2 (ja) |
AU (2) | AU2011322482B2 (ja) |
CA (1) | CA2847197C (ja) |
DK (1) | DK2632446T3 (ja) |
ES (1) | ES2715204T3 (ja) |
RU (1) | RU2013123796A (ja) |
WO (1) | WO2012056044A1 (ja) |
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DK2632446T3 (en) | 2010-10-30 | 2019-04-01 | Univ Oxford Innovation Ltd | TREATMENT OF DUPUYTRY CONTRACT |
JP2015521169A (ja) | 2012-05-01 | 2015-07-27 | プロテオリース リミテッド | 抜歯する方法 |
US20130297023A1 (en) * | 2012-05-07 | 2013-11-07 | Hee-Jeong Im Sampen | Methods and Devices For Treating Intervertebral Disc Disease |
WO2015006469A2 (en) * | 2013-07-11 | 2015-01-15 | 180 Therapeutics Lp | Method of treating fibroproliferative disorders including dupuytren ' s disease with one or more specific human matrix metalloproteinase and a tnf antagonist |
US20180036404A1 (en) | 2015-03-02 | 2018-02-08 | 180 Therapeutics Lp | Method of treating a localized fibrotic disorder using a tnf receptor 2 antagonist |
CA3020327A1 (en) | 2016-04-08 | 2017-10-12 | 180 Therapeutics Lp | Method of treating early stage dupuytren's disease |
WO2018045213A1 (en) * | 2016-09-02 | 2018-03-08 | 180 Therapeutics Lp | Method of treating systemic fibrotic disorders using an il-33/tnf bispecific antibody |
EP3570865A4 (en) * | 2016-09-02 | 2020-05-20 | 180 Therapeutics LP | METHOD FOR THE TREATMENT OF LOCALIZED FIBROTIC DISORDERS USING A BISPECIFIC ANTI-IL-33 / TNF ANTIBODY |
US11564963B2 (en) | 2017-11-22 | 2023-01-31 | Progeneron, Llc | Topical compositions, process of large-scale manufacture, and method of use |
WO2020247808A1 (en) * | 2019-06-07 | 2020-12-10 | Dale Biotech, Llc | Method for treating dupuytren's disease |
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US7431927B2 (en) * | 2005-03-24 | 2008-10-07 | Epitomics, Inc. | TNFα-neutralizing antibodies |
WO2010102262A1 (en) | 2009-03-06 | 2010-09-10 | Halozyme, Inc. | Temperature sensitive mutants of matrix metalloprotease 1 und uses thereof |
EP2403353B1 (en) | 2009-03-06 | 2019-08-14 | Kenneth William Gregg | Composition for controlling fish |
DK2632446T3 (en) | 2010-10-30 | 2019-04-01 | Univ Oxford Innovation Ltd | TREATMENT OF DUPUYTRY CONTRACT |
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AU2011322482A1 (en) | 2013-05-23 |
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ES2715204T3 (es) | 2019-06-03 |
DK2632446T3 (en) | 2019-04-01 |
AU2017204267B2 (en) | 2019-05-23 |
JP2017014266A (ja) | 2017-01-19 |
US20130287760A1 (en) | 2013-10-31 |
CA2847197A1 (en) | 2012-05-03 |
CA2847197C (en) | 2020-11-03 |
WO2012056044A1 (en) | 2012-05-03 |
RU2013123796A (ru) | 2014-12-10 |
US9138458B2 (en) | 2015-09-22 |
US10669334B2 (en) | 2020-06-02 |
EP2632446B1 (en) | 2018-12-12 |
AU2017204267A1 (en) | 2017-07-13 |
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