JP2021500349A - 抗cd47剤ベースの卵巣癌療法 - Google Patents
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- GBABOYUKABKIAF-IELIFDKJSA-N vinorelbine Chemical compound C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC([C@]23[C@H]([C@@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC GBABOYUKABKIAF-IELIFDKJSA-N 0.000 description 1
- 229960002066 vinorelbine Drugs 0.000 description 1
- CILBMBUYJCWATM-PYGJLNRPSA-N vinorelbine ditartrate Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O.OC(=O)[C@H](O)[C@@H](O)C(O)=O.C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC([C@]23[C@H]([C@@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC CILBMBUYJCWATM-PYGJLNRPSA-N 0.000 description 1
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Abstract
Description
本出願は、2017年10月18日に出願された米国仮出願第62/573,835号の利益を主張し、これは、あらゆる目的で参照によりその全体が本明細書に組み込まれる。
本出願は、ASCIIフォーマットで電子的に提出された配列表を含み、その全体が参照により本明細書に組み込まれる。2018年9月26日に作成された前述のASCIIコピーは、41619WO_CRF_sequencelisting.txtという名称であり、サイズは6,241バイトである。
%RO=100−((MFI試験−MFI未染色)/(MFI飽和STD−MFI未染色))×100
抗CD47剤の治療用量で対象を処置するための方法が提供される。本発明の方法は、プライミング剤を対象に投与する工程と、その後に治療上有効な用量の抗CD47剤を対象に投与する工程とを含む。いくつかの実施形態では、治療上有効な用量を投与する工程は、プライミング剤の投与の開始後、少なくとも約3日(例えば、少なくとも約4日、少なくとも約5日、少なくとも約6日、少なくとも約7日、少なくとも約8日、少なくとも約9日、または少なくとも約10日)後に実行される。この期間は、例えば、個体による網状赤血球産生の増強を提供するのに十分である。
本明細書で提供されるのは、卵巣癌を有する個体を処置するか、または対象における卵巣癌のサイズを減少させるための方法であって、以下:対象に対して治療上有効な量の抗CD47抗体;及び任意で、対象に対して治療上有効な量の少なくとも1つの追加の薬剤;を投与する工程を含む、方法である。
「がん」、「新生物」、及び「腫瘍」という用語は、本明細書では互換的に使用され、自律的で無秩序な成長を示し、その結果、細胞増殖に対する制御の有意な喪失を特徴とする異常な成長表現型を示す細胞を指す。本出願における検出、分析、または処置の対象となる細胞としては、前癌性(例えば、良性)、悪性、前転移性、転移性、及び非転移性細胞が挙げられる。ほぼ全ての組織のがんが知られている。「がん負荷」という語句は、対象におけるがん細胞の量またはがんの容積を指す。したがって、がんの負担を軽減するとは、対象のがん細胞の数またはがんの体積を減少させることを指す。本明細書で使用される「がん細胞」という用語は、がん細胞であるか、またはがん細胞に由来する任意の細胞、例えば、がん細胞のクローンを指す。癌腫、肉腫、神経膠芽腫、黒色腫、リンパ腫、骨髄腫などの固形腫瘍、及び白血病などの循環癌を含む、多くの種類のがんが当業者に公知である。がんの例としては、限定するものではないが、卵巣癌、乳癌、結腸癌、肺癌、前立腺癌、肝細胞癌、胃癌、膵臓癌、子宮頸癌、卵巣癌、肝臓癌、膀胱癌、尿路の癌、甲状腺癌、腎臓癌、癌腫、黒色腫、頭頸部癌、及び脳癌が挙げられる。
本明細書に記載される方法は、ベースラインと比較して少なくとも1つの改善されたエンドポイントをもたらす。
本明細書に記載の方法は、抗体(複数可)の投与、すなわち、抗CD47抗体の投与、及びいくつかの実施形態では、追加の抗体の投与を含む。上記のように、「抗体」という用語は、特定の抗原と免疫学的に反応する免疫グロブリン分子への言及を含み、ポリクローナル抗体とモノクローナル抗体の両方を含む。この用語はまた、キメラ抗体(例えば、ヒト化マウス抗体)及びヘテロコンジュゲート抗体などの遺伝子操作された形態を含む。「抗体」という用語はまた、抗原結合能を有するフラグメント(例えば、Fab’、F(ab’)2、Fab、Fv、及びrIgG)を含む、抗体の抗原結合形態を含む。この用語はまた、組換え単鎖Fvフラグメント(scFv)も指す。抗体という用語には、二価または二重特異性分子、ダイアボディ、トリアボディ、及びテトラボディも含まれる。
本明細書に記載の方法は、抗CD47抗体の投与を含む。
本明細書に記載の方法は、治療上有効な用量の組成物、すなわち、治療上有効な用量の抗CD47抗体及び、任意で、追加の薬剤の投与を含む。
本明細書に記載の方法のいくつかの実施形態では、治療上有効な用量の抗CD47抗体を個体に投与する前に、プライミング剤を投与する。適切なプライミング剤は、赤血球新生刺激剤(ESA)、及び/または抗CD47抗体の初回刺激用量を含む。プライミング剤の投与後、網状赤血球産生の増大に有効な期間を与えた後、治療用量の抗CD47抗体が投与される。投与は、参照により本明細書に具体的に組み込まれる同時係属特許出願USSN 14/769,069に記載されている方法に従って行ってもよい。
本明細書に記載の方法では、組成物、例えば、抗CD47抗体及び、任意で、追加の薬剤が対象に投与される。組成物は、非経口、局所、静脈内、腹腔内、腫瘍内、経口、皮下、動脈内、頭蓋内、腹腔内、鼻腔内または筋肉内の手段によって投与されてもよい。典型的な投与経路は、静脈内または腫瘍内であるが、他の経路も同様に効果的であり得る。
本明細書に記載の方法は、抗CD47抗体及び/または追加の薬剤を含む薬学的組成物の投与を含む。
また、本明細書には、抗CD47抗体などの活性薬剤、及び任意で追加の薬剤、及びその製剤、ならびに使用説明書を含むキットが記載されている。このキットは、少なくとも1つの追加の試薬、例えば、化学療法薬物、ESAなどをさらに含んでもよい。キットには、通常、キットの内容の使用目的を示すラベルが含まれている。ラベルという用語には、キット上またはキットとともに提供される、またはキットに別の方法で付随する、任意の書面または記録された資料が含まれる。
いくつかの実施形態では、本明細書に記載される方法は、本明細書に記載される配列;例えば、本明細書に記載の重鎖、軽鎖、及び/またはCDR配列を有する抗体の投与を含む。投与される抗体の配列は、本明細書に記載される配列と例えば、少なくとも95、96、97、98、99、または100%同一であり得る。
第I相臨床試験において、ヒトのがん患者は、0.1mg/kg(n=1)、0.3mg/kg(n=2)、1.0mg/kg(n=6)、及び3.0mg/kg(n=2)でHu−5F9−G4の様々な初回刺激用量を投与された。
卵巣癌を有する5人の女性のがん患者は、単剤療法としてHu−5F9−G4で処置された。2017年7月現在のそれぞれの投与プロトコール及び応答を表Aにまとめている。
卵巣癌患者を、抗CD47抗体の投与のために選択する。
卵巣癌患者を、抗CD47抗体の投与のために選択する。
Claims (69)
- 上皮性卵巣癌を有するヒト対象を処置するか、またはヒト対象における上皮性卵巣癌のサイズを減少させる方法であって、前記対象に抗CD47抗体を投与する工程を含む、前記方法。
- (a)抗CD47抗体の初回刺激用量を対象に投与する工程であって、前記初回刺激用量は約0.5〜約5mg/kgの抗体である、前記工程;及び
(b)治療上有効な用量の抗CD47抗体を対象に投与する工程であって、工程(a)の開始後少なくとも約3〜14日後に、任意で(a)の7日後に行われる、前記工程
を含む、請求項1に記載の方法。 - (a)抗CD47抗体の前記初回刺激用量を、1日目に1mg/kgの抗体の用量で対象に投与する工程;及び、(b)抗CD47抗体の前記治療上有効な用量を、8日目に20mg/kgの抗体、30mg/kgの抗体、45mg/kgの抗体、60mg/kgの抗体、または67.5mg/kgの抗体の用量で対象に投与する工程、を含む、請求項2に記載の方法。
- 上皮性卵巣癌が漿液性腫瘍、粘液性腫瘍、明細胞腫瘍、類内膜腫瘍(endometriod tumor)、移行上皮腫瘍、ブレナー腫瘍、癌肉腫腫瘍、混合上皮腫瘍、境界上皮腫瘍、未分化癌腫瘍、卵管腫瘍、または原発性腹膜腫瘍である、請求項1に記載の方法。
- 前記上皮性卵巣癌が漿液性腫瘍である、請求項1に記載の方法。
- 前記漿液性卵巣癌が、組織学的分析の細分類によって決定される低悪性度または高悪性度である、請求項5に記載の方法。
- 少なくとも1つの追加の薬剤をヒト対象に投与する工程をさらに含む、先行請求項のいずれか1項に記載の方法。
- 卵巣癌を有するヒト対象を処置するか、またはヒト対象における上皮性卵巣癌のサイズを減少させる方法であって、抗CD47抗体を前記ヒト対象に投与する工程;及び、少なくとも1つの追加の薬剤を前記ヒト対象に投与する工程、を含む、前記方法。
- 前記追加の薬剤が、化学療法剤、VEGF阻害剤、PARP阻害剤、免疫チェックポイント阻害剤、免疫抗がん剤、及び葉酸阻害剤の少なくとも1つを含む、請求項8に記載の方法。
- 前記追加の薬剤が化学療法剤である、請求項9に記載の方法。
- 前記化学療法剤が白金(シスプラチン/カルボプラチン)である、請求項10に記載の方法。
- 前記化学療法剤が、タキサン(パクリタキセル(Taxol(登録商標))またはドセタキセル(Taxotere(登録商標)))、ゲムシタビン、アルブミン結合パクリタキセル(nab−パクリタキセル、Abraxane(登録商標))、アルトレタミン(Hexalen(登録商標))、カペシタビン(Xeloda(登録商標))、シクロホスファミド(Cytoxan(登録商標))、エトポシド(VP−16)、ゲムシタビン(Gemzar(登録商標))、イホスファミド(Ifex(登録商標))、イリノテカン(CPT−11、Camptosar(登録商標))、リポソームドキソルビシン(Doxil(登録商標))、メルファラン、ペメトレキセド(Alimta(登録商標))、トポテカン、ビノレルビン(Navelbine(登録商標))、またはトラベクテジン(Yondelis(登録商標))である、請求項10に記載の方法。
- 前記追加の薬剤が、VEGF阻害剤、任意でベバシズマブ(Avastin(登録商標))、レゴラフェニブ(Stivarga(登録商標))、またはアフリベルセプト(Eylea(登録商標))である、請求項9に記載の方法。
- 前記追加の薬剤がPARP阻害剤であり、任意で前記PARP阻害剤がルカパリブ(Rubraca(登録商標))、ニラパリブ(Zejula(登録商標))、オラパリブ(Lynparza(登録商標))、タラゾパリブ(BMN−673)、またはベリパリブ(ABT−888)である、請求項9に記載の方法。
- 前記追加の薬剤が免疫チェックポイント阻害剤であり、任意で、前記追加の薬剤がCTLA4、PD1、及びPDL1の少なくとも1つを阻害する、請求項9に記載の方法。
- 前記追加の薬剤が、葉酸代謝を阻害するかまたは葉酸受容体を標的とする葉酸阻害剤である、請求項9に記載の方法。
- 前記抗CD47抗体及び追加の薬剤が、同時にまたは順次投与される、先行請求項のいずれか1項に記載の方法。
- 前記抗CD47抗体がIgG4 Fcを含む、先行請求項のいずれか1項に記載の方法。
- 前記抗CD47抗体がCD47への結合についてHu5F9−G4と競合する、先行請求項のいずれか1項に記載の方法。
- 前記抗CD47がHu5F9−G4と同じCD47エピトープに結合する、先行請求項のいずれか1項に記載の方法。
- 前記抗CD47抗体がHu5F9−G4である、先行請求項のいずれか1項に記載の方法。
- 前記抗体が、薬学的に許容される賦形剤とともに薬学的組成物として製剤化される、先行請求項のいずれか1項に記載の方法。
- 前記ヒト対象が白金感受性である、先行請求項のいずれか1項に記載の方法。
- 前記ヒト対象が白金耐性である、請求項21を除く先行請求項のいずれか1項に記載の方法。
- 前記抗体が静脈内投与される、先行請求項のいずれか1項に記載の方法。
- 前記抗体が腹腔内投与される、先行請求項のいずれか1項に記載の方法。
- 前記抗体が腫瘍内投与される、先行請求項のいずれか1項に記載の方法。
- 前記抗体の投与がベースラインと比較して対象におけるCA125のレベルを低下させ、任意でCA125のレベルが月に約1回測定される、先行請求項のいずれか1項に記載の方法。
- 前記抗体の投与が、対象におけるCA125のレベルを、ベースラインと比較して少なくとも30〜90、40〜80、50〜70、30、40、50、60、70、80、または90%低下させる、先行請求項のいずれか1項に記載の方法。
- 前記抗体の投与が、任意で画像化により測定されるがんまたはその転移のサイズを、ベースラインと比較して減少させ、任意で、前記画像化はCT/PET/CTまたはMRIであり、最初はベースラインからサイズが増大するがその後減少する疾患が任意で含まれる、先行請求項のいずれか1項に記載の方法。
- 前記抗体の投与が、ベースラインと比較して、CA125、HE4(ヒト精巣上体タンパク質4)、CA−72−4、CA−19−9、及びCEAのうち少なくとも1つのレベルを低下させる、先行請求項のいずれか1項に記載の方法。
- 卵巣癌が上皮性卵巣癌、任意で漿液性腫瘍、粘液性腫瘍、明細胞腫瘍、類内膜腫瘍、移行上皮腫瘍、ブレナー腫瘍、癌肉腫腫瘍、混合上皮腫瘍、境界上皮腫瘍、未分化癌腫瘍、卵管腫瘍、または原発性腹膜腫瘍である、先行請求項のいずれか1項に記載の方法。
- 前記卵巣癌が漿液性腫瘍である、先行請求項のいずれか1項に記載の方法。
- 前記漿液性腫瘍が、組織学的分析によって決定される低悪性度または高悪性度である、請求項33に記載の方法。
- 腫瘍の種類が組織学的分析によって決定される、先行請求項のいずれか1項に記載の方法。
- 初回刺激用量の抗CD47抗体を投与する工程をさらに含む、先行請求項のいずれか1項に記載の方法。
- 初回刺激用量のエリスロポエチン刺激剤を投与する工程をさらに含む、先行請求項のいずれか1項に記載の方法。
- 前記抗CD47抗体が、約0.5〜約5mg/kgの抗体の範囲、任意で1mg/kgの抗体の初回刺激用量として対象に投与される、請求項36のいずれかに記載の方法。
- 前記抗CD47抗体が、約20〜約67.5mg/kgの抗体の範囲、任意で20mg/kgの抗体、30mg/kgの抗体、45mg/kgの抗体、60mg/kgの抗体、または67.5mg/kgの抗体の用量として対象に投与される、先行請求項のいずれか1項に記載の方法。
- 前記抗CD47抗体が、毎週、2週間ごと、または3週間ごとに対象に投与される、先行請求項のいずれか1項に記載の方法。
- (a)前記抗CD47抗体の初回刺激用量を対象に投与する工程であって、前記初回刺激用量は約0.5〜約5mg/kgの抗体である、前記工程;及び
(b)治療上有効な用量の前記抗CD47抗体を対象に投与する工程であって、工程(a)の開始後少なくとも約3〜14日後に、任意で(a)の7日後に行われる、前記工程
を含む、先行請求項のいずれか1項に記載の方法。 - (a)抗CD47抗体の前記初回刺激用量を、1日目に1mg/kgの抗体の用量で対象に投与する工程;及び、(b)抗CD47抗体の前記治療上有効な用量を、8日目に20mg/kgの抗体、30mg/kgの抗体、45mg/kgの抗体、60mg/kgの抗体、または67.5mg/kgの抗体の用量で対象に投与する工程、を含む、請求項41に記載の方法。
- 前記初回刺激用量の有効性が、前記初回刺激用量の投与後の対象の貧血状態に基づいて決定される、請求項36〜42のいずれか1項に記載の方法。
- 対象のヘモグロブリンレベルの低下が8.0g/dL以上である;かつ/または
対象のヘモグロビンレベルの絶対低下が3.0〜3.75g/dL未満である
ならば、前記初回刺激用量が有効であると見なされる、請求項36〜42のいずれか1項に記載の方法。 - 工程(a)の後かつ工程(b)の前に、前記初回刺激用量の投与が有効であったか否かを決定する工程をさらに含む、請求項41に記載の方法。
- 前記決定工程が、網状赤血球カウントを行うことを含み、前記網状赤血球カウントが1Lあたり約100×109個の網状赤血球〜1Lあたり約1000×109個の網状赤血球である場合、前記初回刺激用量の投与が有効であったと決定される、請求項42に記載の方法。
- 前記決定工程が、網状赤血球カウントを行うことを含み、血液中の網状赤血球のパーセンテージが約1.5%を超える場合、前記初回刺激用量の投与が有効であったと決定される、請求項46に記載の方法。
- 前記決定工程が、網状赤血球カウントを行うことを含み、網状赤血球指数が約2%を超える場合、プライミング剤の投与が有効であったと決定される、請求項46に記載の方法。
- 前記初回刺激用量が、約0.05mg/ml〜約0.5mg/mlの濃度の抗CD47抗体を含む注入剤としてヒト対象に投与される、請求項41〜48のいずれか1項に記載の方法。
- 前記注入剤が、少なくとも約1〜3、8〜10、1、2、3、4、5、6、7、8、9、または10時間の期間にわたって送達される、請求項49に記載の方法。
- 前記注入剤が、少なくとも約3時間の期間にわたって送達される、請求項49に記載の方法。
- 前記注入剤が、約2.5時間〜約6時間の期間にわたって送達される、請求項49に記載の方法。
- 前記初回刺激用量が、約6時間〜約3日の期間にわたって連続ポンプによって送達される、請求項41〜48のいずれか1項に記載の方法。
- 前記初回刺激用量が皮下送達される、請求項41〜53のいずれか1項に記載の方法。
- 前記初回刺激用量が、赤血球上のCD47部位の少なくとも約50%〜100%、任意で赤血球上のCD47部位の100%を飽和させる、請求項41〜54のいずれか1項に記載の方法。
- 前記用量が、
対象へのある用量の非標識抗CD47剤の投与後に血液試料を得て、検出可能に標識された抗CD47抗体の飽和用量と組み合わせる、受容体占有率アッセイ;及び
結合のレベルを決定すること
によって決定される、請求項55に記載の方法。 - (b)の前記治療上有効な用量が、ある持続期間にわたって、100、250、500、または1000μg/mlを超える循環レベルの前記抗CD47抗体を達成するのに十分であり、任意で、前記持続期間は少なくとも1〜28日、7〜28日、7〜21日、14〜28日、または21〜28日である、請求項41〜56のいずれか1項に記載の方法。
- 前記持続期間が約1、2、3、または4週間である、請求項57に記載の方法。
- 前記初回刺激用量が1mg/kgの抗体である、請求項41〜58に記載の方法。
- 前記治療上有効な用量が20mg/kgの抗体である、請求項41〜58に記載の方法。
- 前記治療上有効な用量が30mg/kgの抗体である、請求項41〜58に記載の方法。
- 前記治療上有効な用量が45mg/kgの抗体である、請求項41〜58に記載の方法。
- 前記治療上有効な用量が60mg/kgの抗体である、請求項41〜58に記載の方法。
- 前記治療上有効な用量が67.5mg/kgの抗体である、請求項41〜58に記載の方法。
- 前記治療上有効な用量が、約7、14、21、または28日ごとに投与される、請求項41〜64のいずれか1項に記載の方法。
- 前記治療上有効な用量が7日ごとに投与される、請求項41〜65のいずれか1項に記載の方法。
- 非上皮性卵巣癌を有するヒト対象を処置する方法であって、前記対象に抗CD47抗体を投与する工程を含み、任意で、前記非上皮性卵巣癌は悪性性索腫瘍または悪性生殖細胞腫瘍である、前記方法。
- 抗CD47抗体及び少なくとも1つの追加の薬剤を含む組成物であって、任意で、前記追加の薬剤は、化学療法剤、VEGF阻害剤、PARP阻害剤、免疫チェックポイント阻害剤、免疫抗がん剤、または葉酸阻害剤である、前記組成物。
- 抗CD47抗体、少なくとも1つの追加の薬剤、及び使用説明書を備えるキットであって、任意で、前記追加の薬剤は、化学療法剤、VEGF阻害剤、PARP阻害剤、免疫チェックポイント阻害剤、免疫抗がん剤、または葉酸阻害剤である、前記キット。
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PL3697817T3 (pl) | 2017-10-18 | 2023-01-23 | Forty Seven, Inc. | Terapia nowotworu złośliwego jajnika w oparciu o środek anty-cd47 |
WO2019157432A1 (en) | 2018-02-12 | 2019-08-15 | Forty Seven, Inc. | Anti-cancer regimen using anti-cd47 and anti-cd20 antibodies |
WO2020047651A1 (en) * | 2018-09-04 | 2020-03-12 | Trillium Therapeutics Inc. | Cd47 blockade with parp inhibition for disease treatment |
WO2021124073A1 (en) | 2019-12-17 | 2021-06-24 | Pfizer Inc. | Antibodies specific for cd47, pd-l1, and uses thereof |
EP4168449A1 (en) * | 2020-06-22 | 2023-04-26 | MorphoSys AG | Anti-tumor combination therapy comprising anti-cd19 antibody and polypeptides blocking the sirpa-cd47 innate immune checkpoint |
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Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2017049251A2 (en) * | 2015-09-18 | 2017-03-23 | Tioma Therapeutics, Inc. | Therapeutic cd47 antibodies |
WO2017127707A1 (en) * | 2016-01-21 | 2017-07-27 | The Board Of Trustees Of The Leland Stanford Junior University | Treatment of cancer with combinations of immunoregulatory agents |
Family Cites Families (35)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DK3056514T3 (da) | 2008-01-15 | 2019-07-01 | Univ Leland Stanford Junior | Fremgangsmåder til at manipulere fagocytose medieret af cd47 |
US20160095939A1 (en) | 2014-10-07 | 2016-04-07 | Immunomedics, Inc. | Neoadjuvant use of antibody-drug conjugates |
SI2477648T1 (sl) | 2009-09-15 | 2022-09-30 | The Board Of Trustees Of The Leland Stanford Junior University | Sinergijska terapija proti CD47 za krvne rake |
US9151760B2 (en) | 2009-09-29 | 2015-10-06 | The Board Of Trustees Of The Leland Stanford Junior University | Isolation and use of melanoma cancer stem cells |
DK2569013T3 (da) | 2010-05-14 | 2017-02-13 | Univ Leland Stanford Junior | Humaniserede og kimære monoklonale antistoffer til cd47 |
WO2012088309A1 (en) | 2010-12-21 | 2012-06-28 | The Board Of Trustees Of The Leland Stanford Junior University | Therapeutic and diagnostic methods for manipulating phagocytosis through calreticulin and low density lipoprotein-related receptor |
PL2804617T3 (pl) | 2012-01-17 | 2020-11-30 | The Board Of Trustees Of The Leland Stanford Junior University | Reagenty sirp-alfa o wysokim powinowactwie |
WO2014093678A2 (en) | 2012-12-12 | 2014-06-19 | Frazier William A | Therapeutic cd47 antibodies |
CA2903773A1 (en) | 2013-03-15 | 2014-09-25 | The Board Of Trustees Of The Leland Stanford Junior University | Methods for achieving therapeutically effective doses of anti-cd47 agents |
CA2910466A1 (en) | 2013-04-29 | 2014-11-06 | The Board Of Trustees Of The Leland Stanford Junior University | Use of anti-cd47 agents to enhance immunization |
WO2014186761A2 (en) | 2013-05-17 | 2014-11-20 | The Board Of Trustes Of The Leland Stanford Junior University | Methods for determining responsiveness to an anti-cd47 agent |
WO2015138600A2 (en) | 2014-03-11 | 2015-09-17 | The Board Of Trustees Of The Leland Stanford Junior University | Anti sirp-alpha antibodies and bi-specific macrophage enhancing antibodies |
WO2016023001A1 (en) | 2014-08-08 | 2016-02-11 | The Board Of Trustees Of The Leland Stanford Junior University | Multispecific high affinity pd-1 agents and methods of use |
US9546206B2 (en) | 2014-08-08 | 2017-01-17 | The Board Of Trustees Of The Leland Stanford Junior University | High affinity PD-1 agents and methods of use |
EP3209769B1 (en) | 2014-10-24 | 2020-08-05 | The Board of Trustees of the Leland Stanford Junior University | Compositions and methods for inducing phagocytosis of mhc class i positive cells and countering anti-cd47/sirpa resistance |
TWI595006B (zh) | 2014-12-09 | 2017-08-11 | 禮納特神經系統科學公司 | 抗pd-1抗體類和使用彼等之方法 |
US10780117B2 (en) | 2015-01-21 | 2020-09-22 | The Board Of Trustees Of The Leland Stanford Junior University | Macrophages eat cancer cells using their own calreticulin as a guide |
US10358472B2 (en) | 2015-05-06 | 2019-07-23 | The Board Of Trustees Of The Leland Stanford Junior University | High affinity CD47 analogs |
US20180147257A1 (en) | 2015-05-22 | 2018-05-31 | The Board Of Trustees Of The Leland Stanford Junior University | Btn3a ectodomain proteins and methods of use |
WO2017019767A1 (en) | 2015-07-27 | 2017-02-02 | Myosotis, Llc | Inhibition of CXCL12 in Cancer Immunotherapy |
AU2016310348B2 (en) | 2015-08-26 | 2023-01-05 | The Board Of Trustees Of The Leland Stanford Junior University | Enhanced depletion of targeted cells with CD47 blockade and an immune costimulatory agonist |
CA3005911A1 (en) | 2015-12-11 | 2017-06-15 | The Board Of Trustees Of The Leland Stanford Junior University | Treatment of cancer with dual targeting of cd47 and egfr |
WO2017117196A1 (en) | 2015-12-28 | 2017-07-06 | Syndax Pharmaceuticals, Inc. | Combination of hdac inhibitor and anti-pd-l1 antibody for treatment of ovarian cancer |
CN114716552B (zh) | 2016-01-11 | 2024-05-24 | 四十七公司 | 人源化、小鼠或嵌合抗cd47单克隆抗体 |
AU2017250809B2 (en) | 2016-04-15 | 2024-02-29 | The Board Of Trustees Of The Leland Stanford Junior University | Methods for determining and achieving therapeutically effective doses of anti-CD47 agents in treatment of cancer |
EP3493845A4 (en) | 2016-08-03 | 2020-04-15 | The Board of Trustees of the Leland Stanford Junior University | INTERRUPTION OF FC RECEPTOR USE ON MACROPHAGES TO IMPROVE THE EFFECTIVENESS OF ANTI-SIRPALPHA ANTIBODY THERAPY |
US10934331B2 (en) | 2016-08-12 | 2021-03-02 | The Board Of Trustees Of The Leland Stanford Junior University | Methods for enhancing immune responsiveness in an individual toward a target cancer cell population comprising apoptotic cells |
US10995152B2 (en) | 2016-10-26 | 2021-05-04 | The Board Of Trustees Of The Leland Stanford Junior University | Modified immunoglobulin hinge regions to reduce hemagglutination |
WO2018165015A1 (en) | 2017-03-09 | 2018-09-13 | The Board Of Trustees Of The Leland Stanford Junior University | Treatment of pediatric brain tumors with targeting of cd47 pathway |
PL3697817T3 (pl) | 2017-10-18 | 2023-01-23 | Forty Seven, Inc. | Terapia nowotworu złośliwego jajnika w oparciu o środek anty-cd47 |
CA3078430A1 (en) | 2017-10-18 | 2019-04-25 | Forty Seven, Inc. | Treatment of ovarian cancer with anti-cd47 and anti-pd-l1 |
EP3807319A4 (en) | 2018-06-13 | 2022-05-25 | The Board of Trustees of the Leland Stanford Junior University | COMPOSITIONS AND METHODS FOR INDUCING PHAGOCYTOSIS |
US20220091104A1 (en) | 2018-09-28 | 2022-03-24 | The Board Of Trustees Of The Leland Stanford Junior University | Analysis of polymorphisms in sirp-alpha for evaluating response to immunotherapy |
WO2020160285A1 (en) | 2019-02-01 | 2020-08-06 | The Board Of Trustees Of The Leland Stanford Junior University | SIRPα EXPRESSION ON T CELLS IS A BIOMARKER FOR FUNCTIONAL T CELLS DURING EXHAUSTION |
WO2020163692A1 (en) | 2019-02-08 | 2020-08-13 | The Board Of Trustees Of The Leland Stanford Junior University | Treatment of cutaneous t cell lymphoma with targeting of cd47 pathway |
-
2018
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- 2018-10-18 JP JP2020522016A patent/JP7308191B2/ja active Active
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-
2022
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-
2023
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Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2017049251A2 (en) * | 2015-09-18 | 2017-03-23 | Tioma Therapeutics, Inc. | Therapeutic cd47 antibodies |
WO2017127707A1 (en) * | 2016-01-21 | 2017-07-27 | The Board Of Trustees Of The Leland Stanford Junior University | Treatment of cancer with combinations of immunoregulatory agents |
Non-Patent Citations (6)
Title |
---|
CANCER RESEARCH, 2016, VOL.76, NO.14, ABSTRACT 4001, JPN6022041551, ISSN: 0004992129 * |
EUROPEAN JOURNAL OF CANCER, 2014, VOL.50, SUPPL.5, P.S13, JPN6022041552, ISSN: 0004992130 * |
GYNECOLOGIC ONCOLOGY, 2016, VOL.143, NO.2, PP.393-397, JPN6023006175, ISSN: 0004992132 * |
ONCOTARGET, 2017.03, VOL.8, NO.24, PP.39021-39032, JPN6022041547, ISSN: 0004992127 * |
PLOS ONE, 2015, VOL.10, NO.9, ARTICLE NO.E0137345, PP.1-23, JPN6022041553, ISSN: 0004992131 * |
PNAS, 2012, VOL.109, NO.17, PP.6662-6667, JPN6022041548, ISSN: 0004992128 * |
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