JP6204915B2 - 悪液質治療 - Google Patents
悪液質治療 Download PDFInfo
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Description
本出願は、2011年9月23日に出願された米国仮特許出願第61/538,309号明細書からの優先権を主張するものである。
従来の免疫学的及び分子生物学的技法を伴う方法が、本明細書で記載される。免疫学的方法(例えば、抗原−Ab複合体の検出及び位置確認のためのアッセイ、免疫沈降反応、イムノブロッティング等)は、当該技術分野で一般的に既知であり、Current Protocols in Immunology、Coliganら編集、John Wiley&Sons,ニューヨークなどの方法学論文に記載されている。分子生物学の技法は、Molecular Cloning:A Laboratory Manual、第2版、1−3巻、Sambrookら編集、Cold Spring Harbor Laboratory Press、ニューヨーク州コールドスプリングハーバー、2001年;及びCurrent Protocols in Molecular Biology、Ausubelら編集、Greene Publishing and Wiley−Interscience、ニューヨークなどの論文で詳細に記載されている。Ab法は、Handbook of Therapeutic Abs、Dubel,S.編集、Wiley−VCH、2007年に記載されている。医学的治療の一般的な方法は、McPhee及びPapadakis著、Current Medical Diagnosis and Treatment 2010年、第49版、McGraw−Hill Medical、2010年;及びFauciら著、Harrison’s Principles of Internal Medicine、第17版、McGraw−Hill Professional、2008年に記載されている。
本明細書に記載の組成物及び方法は、対象における悪液質の少なくとも1つの特性を改善するために有効な、及び/又は悪液質(特に、癌関連悪液質)を有する哺乳動物対象の生存期間を延長させるために有効な、IL−1α標的化剤の量を含有する医薬組成物を対象に投与することによって、哺乳動物対象における悪液質を治療するために有用である。哺乳動物対象は、ヒト、イヌ、ネコ、ウマ、ウシ、ヒツジ、ヤギ及びブタを含める悪液質に冒された任意の対象であり得る。ヒト対象は、男性、女性、成人、小児、又は高齢者(65歳以上)であり得る。哺乳動物対象は、癌(特に、転移性癌、固形腫瘍癌、並びにステージII、III、又はIVの癌)、HIV感染症、TB、COPD、CHF、慢性腎不全、ホルモン失調症、重度外傷(例えば、火傷)、代謝亢進(例えば、所定の対象に関する正常値を少なくとも6bpm超える持続しかつ上昇した心拍数)、過剰な交感神経活動、超炎症性状態(例えば、CRPレベルの上昇、IL−6レベルの増加、TNFαレベルの増加、及び/又はIFNγレベルの増加)、二か月以内の>5lbの体重減少、及び/又は<20cal/kgの推定された1日のカロリー摂取量を有する対象であり得る。癌を有する対象は、24、18、12、又は6ヶ月未満の期待寿命を有する対象であり得る。対象はまた、ステロイド、栄養補給、及び/又は食欲増進剤で処置中、又は処置された対象であってもよい。
IL−1αに特異的に結合し、対象における悪液質の特性を低減する及び/又は悪液質を有する哺乳動物対象の生存期間を延長させる任意の好適なタイプのAb又はその他の生物学的薬剤(例えば、IL−1受容体などのIL−1α結合成分を含める融合タンパク質)が、本発明で使用され得る。例えば、使用される抗−IL−1αは、mAb、ポリクローナルAb、mAbの混合物、又はAb断片若しくはscFvなどの操作されたAb様分子であり得る。AbのKaは、好ましくは少なくとも1×109M−1以上(例えば、9×1010M−1、8×1010M−1、7×1010M−1、6×1010M−1、5×1010M−1、4×1010M−1、3×1010M−1、2×1010M−1、又は1×1010M−1を超える)である。好ましい実施形態では、本発明は、(i)ヒトIL−1αに対して非常に高い結合親和性(例えば、少なくともナノモル又はピコモルの)を呈する抗原に結合する可変領域と、(ii)定常領域とを含有する完全なヒトmAbを利用する。ヒトAbは、IgG1であることが好ましいが、これはIgM、IgA、若しくはIgE、又はIgG2、IgG3、若しくはIgG4などのサブクラスなどの異なるイソ型であってもよい。特に有用なmAbの一例は、MABp1であり、これは2009年6月1日に出願された米国特許出願第12/455,458号明細書に記載されるIL−1αに特異的なIgG1 mAbである。その他の有用なmAbは、MABp1の少なくとも1つのCDR、しかし好ましくは全てのCDRを含有するものである。CDRは、Ofranら著、J.Immunol.、181:6230、2008年;及びAntibody Engineering 第2巻、第2版、Konterman及びDubel(編集)、Springer、2010年に記載されるような既知の方法により決定されてもよい。
抗−IL−1α Ab組成物は、投与のモード及び経路並びに標準的医薬調製法に基づいて選択される薬学的に許容し得る担体(例えば、無菌生理食塩水)中で動物又はヒトに投与され得る。薬学的に許容し得る担体、並びに医薬品製剤の列挙は、レミントンの薬剤科学(Remington’s Pharmaceutical Sciences)、本分野における標準的テキスト、及びUSP/NFで見ることができる。その他の物質が組成物に添加されてもよく、組成物を安定化及び/若しくは保存するために、並びに/又は対象へのこれらの投与を容易にするためのその他の工程が使用されてもよい。
Xilonix(商標)は、安定化等張緩衝液(pH 6.4)中、15mg/mLのMABp1の無菌注射可能液体製剤である。各々の10mLのI型ホウ珪酸ガラス血清バイアルは、4、5又は10mLの製剤を含有し、20mmのDaikyo Flurotecブチルゴム製ストッパー及びフリップオフアルミニウムシールで密封する。製剤を、室温までの可動域が許容されて、5±3℃で保管する。製剤の正確な組成を以下に示す。
計算された容量を、好適な注射器を用いて、薬剤(mAb)含有バイアルから抜き取る。次いで、薬剤を、100mLの通常生理食塩水(0.9%のNaCl)を含有する小型IVバッグに注入し、反転させることで混合する。希釈した製剤は、投与前3時間にわたって室温で保管することができ、これを、投与後症状の徴候について対象を監視しながら、1時間にわたって注入する。輸注セット内に保持され得るいずれの製剤も送達させるために、輸注に最小限30mLの通常の生理食塩水を追加する。
背景:炎症誘発性サイトカインIL−1αは、食欲不振−悪液質症候群、筋肉質量の減少に関連する複合代謝障害及び病的炎症応答で重要な役割を果たす。MABp1は、IL−1αに対して高い親和性を有する最初の完全なヒトモノクローナル抗体である。第I相の患者のコホートにおける身体構成、栄養摂取及び生活の質に及ぼすMABp1の効果を判定した。
実施例2に記載された臨床試験で登録され、処置された患者の大部分は、難治性転移性結腸直腸癌を有した(42人中14人)。DEXAで評価された18人の対象のうち、7人が転移性結腸直腸癌を有し、これら7人のうち5人がLBTの増加で応答した。これら患者の7人全てについてのLBTの平均増加は3%であって、応答した対象については、増加平均値は4.6%であった。この臨床試験で登録された対象を、RECIST 1.1を用いて腫瘍反応についても評価した。それに伴い、疾患進行のX線検査の証拠のために、一部の対象は投与を中止した。結腸直腸癌を有する14人の患者の中では、生存期間中央値は129日(4.3ヶ月)であった(これらデータポイントの4つが中途で打ち切られた)。試験薬の少なくとも3用量を受容した10人/14人(71%)の患者については、生存期間中央値は224日(7.5ヶ月)であった。生存期間中央値はまた、LBTの増加と密接に関連した。ベースラインから8週までのLBTの増加の客観的証拠を有した5人(36%)の患者については、生存期間中央値は、474日(15.8ヶ月)であった。一方、LBT増加の証拠を示さなかった9人の患者は、72日(2.4ヶ月)の生存期間中央値を示したに過ぎない。同様な集団で実施された試験に基づくと、難治性結腸直腸癌患者についての予期される全生存期間は、約4.6ヶ月である(Jonker,D.ら著、Cetuximab for the Treatment of Colorectal Cancer、N Engl J Med 2006;357:2040−8)。
平均で5つの過去の全身的化学療法レジメンに対して難治性の進行性癌を有する合計で42人の患者(女性57%が、年齢中央値61歳)が、実施例2に記載される臨床試験に登録した。結腸直腸癌は、試験集団全体の三分の一(14人/42人)を占める最もよくみられる悪性腫であることを見出した。23人(55%)の患者は、3つ以上のサイクルを完了し、一方ベースライン及びサイクル3終了時のDEXA測定は、18人の患者に有効であった。分析時までに、合計で18人/42人(43%)の死亡が報告された。平均生存期間は、161日の生存期間中央値で、278±38日であった。
実施例2に記載される試験において、合計で18人の患者が、スクリーニング時及びサイクル3の15日目に有効なDEXA測定値を有し、そのうち12人/18人(67%)が応答患者(≧0kgのLBT変化)であった。図1に示すように、応答患者の中での全生存期間は、377±286日(中央値339日)であり、非応答患者については、313±226日(中央値277日)であった。応答患者群では、8人の患者が中途打ち切りされ、4人が死亡した。非応答患者の中では5人/6人の患者が死亡した(対数順位検定p=0.143)。
本発明は、その詳細な説明と共に記載されてきたが、前述の説明は例示の目的のためであり、添付の特許請求の範囲によって定義される本発明の範囲を限定するよう意図するものではないことを理解されたい。その他の態様、利点、及び修正形態は、以下の特許請求の範囲内にある。
Claims (14)
- 癌を有する人対象における除脂肪体重の減少を軽減するための医薬組成物であって、薬学的に許容し得る担体と、抗−IL−1α抗体(Ab)を前記対象における除脂肪体重の減少を軽減するために有効な量で含むことを特徴とする医薬組成物。
- 請求項1に記載の医薬組成物において、前記抗−IL−1α Abがモノクローナル抗体(mAb)であることを特徴とする医薬組成物。
- 請求項2に記載の医薬組成物において、前記mAbがIgG1であることを特徴とする医薬組成物。
- 請求項2に記載の医薬組成物において、前記mAbが、MABp1の相補性決定領域を含むことを特徴とする医薬組成物。
- 請求項2に記載の医薬組成物において、前記mAbがMABp1であることを特徴とする医薬組成物。
- 請求項1に記載の医薬組成物において、前記対象の体重を増加させる効能を有することを特徴とする医薬組成物。
- 請求項1に記載の医薬組成物において、前記対象の食欲を改善する効能を有することを特徴とする医薬組成物。
- 請求項1に記載の医薬組成物において、前記対象が末期癌を有する人を含むことを特徴とする医薬組成物。
- 請求項1に記載の医薬組成物において、前記対象の筋肉量を増加させる効能を有することを特徴とする医薬組成物。
- 癌と、悪液質に関連する除脂肪体重の減少を有する人対象における寿命を前記対象の前記予測された寿命に比較して少なくとも10%まで延ばすための医薬組成物であって、薬学的に許容し得る担体と、抗−IL−1α抗体(Ab)を含むことを特徴とする医薬組成物。
- 請求項10に記載の医薬組成物において、前記抗−IL−1α Abがモノクローナル抗体(mAb)であることを特徴とする医薬組成物。
- 請求項11に記載の医薬組成物において、前記mAbが、MABp1であることを特徴とする医薬組成物。
- 請求項10に記載の医薬組成物において、前記対象が末期癌を有する人を含むことを特徴とする医薬組成物。
- 請求項10に記載の医薬組成物において、前記医薬組成物の用量が、約0.2乃至20mg/kg体重であることを特徴とする医薬組成物。
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Families Citing this family (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
PT2582391T (pt) | 2010-06-18 | 2019-01-11 | Xbiotech Inc | Tratamento da artrite |
DK2608808T3 (en) | 2010-08-23 | 2017-04-24 | Xbiotech Inc | TREATMENT OF NEOPLASTIC DISEASES |
US9724409B2 (en) | 2011-04-01 | 2017-08-08 | Xbiotech, Inc. | Treatment of inflammatory skin disease |
KR102039198B1 (ko) | 2011-09-23 | 2019-10-31 | 엑스바이오테크, 인크. | 악액질 치료법 |
US9545441B2 (en) | 2012-09-18 | 2017-01-17 | Xbiotech, Inc. | Treatment of diabetes |
US10485502B2 (en) * | 2016-12-20 | 2019-11-26 | General Electric Company | System and method for assessing muscle function of a patient |
JP7145162B2 (ja) | 2017-02-16 | 2022-09-30 | ヤンセン バイオテク,インコーポレイテッド | 化膿性汗腺炎の処置 |
US10975146B2 (en) | 2018-06-29 | 2021-04-13 | Cedars-Sinai Medical Center | Interleukin-1 inhibition for combination treatment of pancreatic cancer |
Family Cites Families (60)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CH652145A5 (de) | 1982-01-22 | 1985-10-31 | Sandoz Ag | Verfahren zur in vitro-herstellung von hybridomen welche humane monoklonale antikoerper erzeugen. |
US5672347A (en) | 1984-07-05 | 1997-09-30 | Genentech, Inc. | Tumor necrosis factor antagonists and their use |
US5168062A (en) | 1985-01-30 | 1992-12-01 | University Of Iowa Research Foundation | Transfer vectors and microorganisms containing human cytomegalovirus immediate-early promoter-regulatory DNA sequence |
US4965198A (en) | 1985-12-24 | 1990-10-23 | Konica Corporation | Monoclonal antibody and method of manufacturing hybridoma producing the same |
DE3631229A1 (de) | 1986-09-13 | 1988-03-24 | Basf Ag | Monoklonale antikoerper gegen humanen tumornekrosefaktor (tnf) und deren verwendung |
DK590387A (da) | 1986-11-13 | 1988-05-14 | Otsuka Pharma Co Ltd | Antistoffer mod interleukin-1 |
US5034316A (en) | 1987-03-30 | 1991-07-23 | The Regents Of The University Of California | In vitro human monoclonal IgG rheumatoid factor autoantibody |
FR2640146B1 (fr) | 1988-12-08 | 1993-12-24 | Commissariat A Energie Atomique | Anticorps monoclonaux anti-interleukines 1(alpha) et 1(beta), leur procede de production et applications desdits anticorps a la detection des interleukines 1(alpha) et 1(beta) et en therapeutique |
US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
CA2049342A1 (en) | 1989-03-27 | 1990-09-28 | Sally Bolmer | Formulations for stabilizing of igm antibodies |
GB9122820D0 (en) | 1991-10-28 | 1991-12-11 | Wellcome Found | Stabilised antibodies |
JPH08502300A (ja) | 1992-10-14 | 1996-03-12 | スターリング ウィンスロップ アイエヌシー. | 治療および診断像形成組成物および方法 |
ES2159529T5 (es) | 1993-03-05 | 2011-03-09 | Bayer Corporation | Anticuerpos monoclonales humanos anti-tnf alfa. |
US5959085A (en) | 1993-11-23 | 1999-09-28 | Schering Corporation | Human monoclonal antibodies against human cytokines and methods of making and using such antibodies |
EP0659766A1 (en) | 1993-11-23 | 1995-06-28 | Schering-Plough | Human monoclonal antibodies against human cytokines and methods of making and using such antibodies |
GB9509620D0 (en) | 1995-05-12 | 1995-07-05 | Nat Blood Authority | Transepithelial transport of molecular species |
US6140470A (en) | 1995-06-30 | 2000-10-31 | Yale University | Human monoclonal anti-tumor antibodies |
US6090382A (en) | 1996-02-09 | 2000-07-18 | Basf Aktiengesellschaft | Human antibodies that bind human TNFα |
SE9802402D0 (sv) | 1998-07-03 | 1998-07-03 | Karolinska Innovations Ab | Method of diagnosing cardiovascular disease and early atherosclerosis |
US20030040617A9 (en) | 1999-03-12 | 2003-02-27 | Rosen Craig A. | Nucleic acids, proteins and antibodies |
US20030232054A1 (en) | 2000-01-25 | 2003-12-18 | Tang Y. Tom | Novel nucleic acids and polypeptides |
US6623736B2 (en) | 2000-05-02 | 2003-09-23 | Edward L. Tobinick | Interleukin antagonists for the treatment of neurological, retinal and muscular disorders |
AU2007202323C1 (en) | 2000-06-29 | 2012-04-12 | Abbvie Inc. | Dual specificity antibodies and methods of making and using |
WO2002033094A1 (fr) | 2000-10-19 | 2002-04-25 | Kyowa Hakko Kogyo Co., Ltd. | Anticorps inhibant l'activite vplf |
US20030026806A1 (en) | 2000-10-27 | 2003-02-06 | Amgen Inc. | Antibodies and other selective IL-1 binding agents that allow binding to IL-1 receptor but not activation thereof |
US7211602B2 (en) | 2001-11-16 | 2007-05-01 | Als Therapy Development Foundation, Inc. | Treatment of neurodegenerative disorders through the modulation of the polyamine pathway |
CN104178491B (zh) | 2002-09-06 | 2018-07-03 | 安姆根有限公司 | 治疗性人抗-il-1r1单克隆抗体 |
JP4450644B2 (ja) | 2003-03-03 | 2010-04-14 | 日本化薬株式会社 | Amf類を有効成分とする医薬製剤 |
US20040224893A1 (en) | 2003-05-06 | 2004-11-11 | Li-Hsien Wang | Methods of using IL-1 antagonists to treat neointimal hyperplasia |
HN2004000285A (es) | 2003-08-04 | 2006-04-27 | Pfizer Prod Inc | ANTICUERPOS DIRIGIDOS A c-MET |
US7799327B2 (en) | 2003-12-24 | 2010-09-21 | Henry John Smith | Autoantibodies utilized as carrier agents for pharmaceutical compounds used in cancer treatment |
US7105183B2 (en) | 2004-02-03 | 2006-09-12 | The Regents Of The University Of California | Chlorite in the treatment of neurodegenerative disease |
WO2006001967A2 (en) | 2004-05-25 | 2006-01-05 | Sloan-Kettering Institute For Cancer Research | Migrastatin analogs in the treatment of cancer |
US20050276807A1 (en) | 2004-06-15 | 2005-12-15 | Advanced Biotherapy, Inc. | Treatment of acne |
WO2006036936A2 (en) | 2004-09-27 | 2006-04-06 | Bridge Pharma, Inc. | The s-isomer of 2-{2-[n-(2-indanyl)-n-phenylamino]ethyl}piperidine and other dermal anesthetic agents |
KR101281501B1 (ko) | 2004-12-09 | 2013-07-15 | 얀센 바이오테크 인코포레이티드 | 항인테그린 면역 컨쥬게이트, 방법 및 용도 |
US8187817B2 (en) | 2005-08-02 | 2012-05-29 | Xbiotech, Inc. | Diagnosis, treatment, and prevention of vascular disorders using IL-1 autoantibodies |
US20090215992A1 (en) | 2005-08-19 | 2009-08-27 | Chengbin Wu | Dual variable domain immunoglobulin and uses thereof |
US7612181B2 (en) | 2005-08-19 | 2009-11-03 | Abbott Laboratories | Dual variable domain immunoglobulin and uses thereof |
JP5312028B2 (ja) | 2005-09-28 | 2013-10-09 | サイトス バイオテクノロジー アーゲー | インターロイキン−1コンジュゲート及びその使用 |
WO2007120828A1 (en) | 2006-04-14 | 2007-10-25 | Novartis Ag | Use of il-i antibodies for treating ophthalmic disorders |
ES2384278T3 (es) | 2006-05-15 | 2012-07-03 | Xbiotech, Inc | IL-1-alfa para su uso en un procedimiento de tratamiento de placas ateroscleróticas |
US20110008282A1 (en) | 2006-05-15 | 2011-01-13 | Xbiotech, Inc. | IL-1alpha immunization induces autoantibodies protective against atherosclerosis |
AU2007252990B2 (en) | 2006-05-22 | 2011-10-27 | Xbiotech Inc. | Treatment of cancer with anti-IL-1alpha antibodies |
RS53168B (en) | 2006-05-30 | 2014-06-30 | Genentech Inc. | Antibodies and Immunoconjugates and Their Use |
WO2008082651A2 (en) | 2006-12-29 | 2008-07-10 | Abbott Laboratories | Dual-specific il-1a/ il-1b antibodies |
EP2265125B1 (en) | 2008-04-15 | 2019-08-14 | SARcode Bioscience Inc. | Topical lfa-1 antagonists for use in localized treatment of immune related disorders |
PL2285409T3 (pl) * | 2008-05-30 | 2016-10-31 | Przeciwciała il-1 alfa | |
WO2010030979A2 (en) | 2008-09-12 | 2010-03-18 | Xbiotech, Inc. | Targeting pathogenic monocytes |
EP2391652A4 (en) * | 2009-01-29 | 2013-01-02 | Abbott Lab | IL-1 BINDING PROTEINS |
EP2488201A4 (en) | 2009-10-15 | 2013-12-25 | Abbvie Inc | IL-1 BINDING PROTEINS |
PT2582391T (pt) | 2010-06-18 | 2019-01-11 | Xbiotech Inc | Tratamento da artrite |
DK2608808T3 (en) | 2010-08-23 | 2017-04-24 | Xbiotech Inc | TREATMENT OF NEOPLASTIC DISEASES |
US9724409B2 (en) | 2011-04-01 | 2017-08-08 | Xbiotech, Inc. | Treatment of inflammatory skin disease |
US20120251548A1 (en) | 2011-04-01 | 2012-10-04 | Xbiotech, Inc. | Treatment of Dermatological Pathologies |
KR102039198B1 (ko) | 2011-09-23 | 2019-10-31 | 엑스바이오테크, 인크. | 악액질 치료법 |
US20130195877A1 (en) | 2012-01-31 | 2013-08-01 | Xbiotech, Inc. | Treatment of cachexia by targeting interleukin-1 beta |
US9545441B2 (en) | 2012-09-18 | 2017-01-17 | Xbiotech, Inc. | Treatment of diabetes |
AU2013327501B2 (en) | 2012-10-04 | 2018-08-09 | Xbiotech Inc. | Treating vascular disease and complications thereof |
CN104684581A (zh) | 2012-10-04 | 2015-06-03 | 埃克斯生物科技公司 | 精神病症的治疗 |
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AU2012312225A1 (en) | 2014-04-10 |
JP2014526559A (ja) | 2014-10-06 |
ES2695102T3 (es) | 2019-01-02 |
US20130078258A1 (en) | 2013-03-28 |
KR20140078690A (ko) | 2014-06-25 |
CN103906536A (zh) | 2014-07-02 |
HK1199616A1 (en) | 2015-07-10 |
KR102039198B1 (ko) | 2019-10-31 |
IL231622A0 (en) | 2014-05-28 |
CA2849710A1 (en) | 2013-03-28 |
CN108404127A (zh) | 2018-08-17 |
US10202449B2 (en) | 2019-02-12 |
EP2750709A2 (en) | 2014-07-09 |
PT2750709T (pt) | 2018-11-22 |
MX2014003402A (es) | 2015-03-05 |
US20180037647A1 (en) | 2018-02-08 |
EP2750709B1 (en) | 2018-08-15 |
CA2849710C (en) | 2020-04-28 |
ZA201402057B (en) | 2016-08-31 |
DK2750709T3 (en) | 2018-12-03 |
EP2750709A4 (en) | 2015-06-10 |
US9809649B2 (en) | 2017-11-07 |
AU2012312225B2 (en) | 2017-10-05 |
WO2013043973A2 (en) | 2013-03-28 |
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