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- 238000000034 method Methods 0.000 claims description 46
- 239000000203 mixture Substances 0.000 claims description 35
- 102100025221 CD70 antigen Human genes 0.000 claims description 16
- 101000934356 Homo sapiens CD70 antigen Proteins 0.000 claims description 16
- 206010028980 Neoplasm Diseases 0.000 claims description 16
- 201000011510 cancer Diseases 0.000 claims description 16
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims description 12
- 208000031261 Acute myeloid leukaemia Diseases 0.000 claims description 12
- 201000003793 Myelodysplastic syndrome Diseases 0.000 claims description 12
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 12
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 claims description 10
- 210000003289 regulatory T cell Anatomy 0.000 claims description 10
- NFGXHKASABOEEW-UHFFFAOYSA-N 1-methylethyl 11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate Chemical compound COC(C)(C)CCCC(C)CC=CC(C)=CC(=O)OC(C)C NFGXHKASABOEEW-UHFFFAOYSA-N 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 8
- 230000004044 response Effects 0.000 claims description 8
- 229940124597 therapeutic agent Drugs 0.000 claims description 8
- NMUSYJAQQFHJEW-KVTDHHQDSA-N 5-azacytidine Chemical compound O=C1N=C(N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 NMUSYJAQQFHJEW-KVTDHHQDSA-N 0.000 claims description 6
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 claims description 6
- 239000002246 antineoplastic agent Substances 0.000 claims description 6
- 229960002756 azacitidine Drugs 0.000 claims description 6
- 210000004027 cell Anatomy 0.000 claims description 6
- 229940127089 cytotoxic agent Drugs 0.000 claims description 6
- 230000004083 survival effect Effects 0.000 claims description 6
- LQBVNQSMGBZMKD-UHFFFAOYSA-N venetoclax Chemical compound C=1C=C(Cl)C=CC=1C=1CC(C)(C)CCC=1CN(CC1)CCN1C(C=C1OC=2C=C3C=CNC3=NC=2)=CC=C1C(=O)NS(=O)(=O)C(C=C1[N+]([O-])=O)=CC=C1NCC1CCOCC1 LQBVNQSMGBZMKD-UHFFFAOYSA-N 0.000 claims description 6
- 229960001183 venetoclax Drugs 0.000 claims description 6
- 229940124307 fluoroquinolone Drugs 0.000 claims description 5
- 230000033581 fucosylation Effects 0.000 claims description 5
- MFRNYXJJRJQHNW-DEMKXPNLSA-N (2s)-2-[[(2r,3r)-3-methoxy-3-[(2s)-1-[(3r,4s,5s)-3-methoxy-5-methyl-4-[methyl-[(2s)-3-methyl-2-[[(2s)-3-methyl-2-(methylamino)butanoyl]amino]butanoyl]amino]heptanoyl]pyrrolidin-2-yl]-2-methylpropanoyl]amino]-3-phenylpropanoic acid Chemical compound CN[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N(C)[C@@H]([C@@H](C)CC)[C@H](OC)CC(=O)N1CCC[C@H]1[C@H](OC)[C@@H](C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 MFRNYXJJRJQHNW-DEMKXPNLSA-N 0.000 claims description 4
- IEDXPSOJFSVCKU-HOKPPMCLSA-N [4-[[(2S)-5-(carbamoylamino)-2-[[(2S)-2-[6-(2,5-dioxopyrrolidin-1-yl)hexanoylamino]-3-methylbutanoyl]amino]pentanoyl]amino]phenyl]methyl N-[(2S)-1-[[(2S)-1-[[(3R,4S,5S)-1-[(2S)-2-[(1R,2R)-3-[[(1S,2R)-1-hydroxy-1-phenylpropan-2-yl]amino]-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl]-3-methoxy-5-methyl-1-oxoheptan-4-yl]-methylamino]-3-methyl-1-oxobutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]-N-methylcarbamate Chemical group CC[C@H](C)[C@@H]([C@@H](CC(=O)N1CCC[C@H]1[C@H](OC)[C@@H](C)C(=O)N[C@H](C)[C@@H](O)c1ccccc1)OC)N(C)C(=O)[C@@H](NC(=O)[C@H](C(C)C)N(C)C(=O)OCc1ccc(NC(=O)[C@H](CCCNC(N)=O)NC(=O)[C@@H](NC(=O)CCCCCN2C(=O)CCC2=O)C(C)C)cc1)C(C)C IEDXPSOJFSVCKU-HOKPPMCLSA-N 0.000 claims description 4
- 230000005888 antibody-dependent cellular phagocytosis Effects 0.000 claims description 4
- 230000009827 complement-dependent cellular cytotoxicity Effects 0.000 claims description 4
- 239000012636 effector Substances 0.000 claims description 4
- 229940075628 hypomethylating agent Drugs 0.000 claims description 4
- 239000002955 immunomodulating agent Substances 0.000 claims description 4
- 230000002584 immunomodulator Effects 0.000 claims description 4
- 229940121354 immunomodulator Drugs 0.000 claims description 4
- 108010093470 monomethyl auristatin E Proteins 0.000 claims description 4
- 108010059074 monomethylauristatin F Proteins 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 230000001225 therapeutic effect Effects 0.000 claims description 4
- 238000011269 treatment regimen Methods 0.000 claims description 4
- 206010066901 Treatment failure Diseases 0.000 claims description 2
- 238000001990 intravenous administration Methods 0.000 claims description 2
- 238000002560 therapeutic procedure Methods 0.000 claims description 2
- 238000011282 treatment Methods 0.000 claims description 2
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
Description
本発明は、以下の実施例を参照することによってより十分に理解されるであろう。しかし、それらは本発明の範囲の制限と解釈されてはならない。本明細書で記載される実施例及び実施形態は、単に例示目的であり、それを考慮して種々の改変又は変更が当業者に示唆され、本出願及び添付の特許請求の範囲の趣旨及び範囲内に含まれるべきであるということは理解される。
例えば、本発明は以下の実施形態を包含する：
［実施形態１］対象においてCD70発現がんを処置する方法であって、対象に非フコシル化抗CD70抗体の治療有効量を投与することを含み、前記方法は、対象においてがん細胞の枯渇をもたらし、対象においてCD70+制御性T細胞(CD70+Treg)の枯渇をもたらさず、抗CD70抗体が、抗CD70抗体のCDRがKabat番号付けスキームによって規定される、配列番号1の3つのCDRを含む重鎖可変領域、配列番号2の3つのCDRを含む軽鎖可変領域及びFcドメインを含み、がんが骨髄異形成症候群(MDS)及び急性骨髄性白血病(AML)からなる群から選択される、方法。
［実施形態２］抗CD70抗体が、配列番号1のアミノ酸配列に対して少なくとも85%同一のアミノ酸配列を含む重鎖可変領域及び配列番号2のアミノ酸配列に対して少なくとも85%同一のアミノ酸配列を含む軽鎖可変領域を含む、実施形態1に記載の方法。
［実施形態３］抗CD70抗体が、配列番号1のアミノ酸配列を含む重鎖可変領域及び配列番号2のアミノ酸配列を含む軽鎖可変領域を含む、実施形態1に記載の方法。
［実施形態４］Fcドメインが、抗体依存性細胞傷害(ADCC)、抗体依存性細胞貪食(ADCP)及び補体依存性細胞傷害(CDC)のうち1つ以上を媒介する抗体エフェクタードメインである、実施形態1から3のいずれかに記載の方法。
［実施形態５］Fcドメインが、ADCCを媒介する抗体エフェクタードメインである、実施形態1から3のいずれかに記載の方法。
［実施形態６］FcドメインがヒトFcドメインである、実施形態1から5のいずれかに記載の方法。
［実施形態７］抗CD70抗体がボルセツズマブである、実施形態1から6のいずれかに記載の方法。
［実施形態８］抗体が治療剤にコンジュゲートされている、実施形態1から7のいずれかに記載の方法。
［実施形態９］治療剤が、化学療法剤又は免疫調節剤である、実施形態8に記載の方法。
［実施形態１０］治療剤が化学療法剤である、実施形態8に記載の方法。
［実施形態１１］化学療法剤が、モノメチルアウリスタチンE(MMAE)又はモノメチルアウリスタチンF(MMAF)である、実施形態10に記載の方法。
［実施形態１２］治療剤が免疫調節剤である、実施形態8に記載の方法。
［実施形態１３］前記方法が抗CD70抗体の集団を投与することを含み、抗CD70抗体の集団中の各抗体が、抗CD70抗体のCDRがKabat番号付けスキームによって規定される、配列番号1の3つのCDRを含む重鎖可変領域、配列番号2の3つのCDRを含む軽鎖可変領域及びFcドメインを含み、抗CD70抗体の集団中の抗CD70抗体の少なくとも50%がコアフコシル化を欠く、実施形態1から12のいずれかに記載の方法。
［実施形態１４］抗CD70抗体の集団中の抗CD70抗体の少なくとも70%が、コアフコシル化を欠く、実施形態13に記載の方法。
［実施形態１５］抗CD70抗体の集団中の抗CD70抗体の少なくとも90%が、コアフコシル化を欠く、実施形態13に記載の方法。
［実施形態１６］がんがMDSである、実施形態1から15のいずれかに記載の方法。
［実施形態１７］MDSが再発性又は難治性MDSである、実施形態16に記載の方法。
［実施形態１８］対象が、MDSのための以前の低メチル化剤(HMA)療法後に処置失敗を経験した、実施形態17に記載の方法。
［実施形態１９］がんがAMLである、実施形態1から15のいずれかに記載の方法。
［実施形態２０］AMLが再発性又は難治性AMLである、実施形態19に記載の方法。
［実施形態２１］対象が、AMLを処置するために2つの以前の処置レジメンを受けた、実施形態20に記載の方法。
［実施形態２２］対象が、AMLを処置するために3つの以前の処置レジメンを受けた、実施形態20に記載の方法。
［実施形態２３］がん細胞の少なくとも約0.1%、少なくとも約1%、少なくとも約2%、少なくとも約3%、少なくとも約4%、少なくとも約5%、少なくとも約6%、少なくとも約7%、少なくとも約8%、少なくとも約9%、少なくとも約10%、少なくとも約15%、少なくとも約20%、少なくとも約25%、少なくとも約30%、少なくとも約35%、少なくとも約40%、少なくとも約45%、少なくとも約50%、少なくとも約60%、少なくとも約70%又は少なくとも約80%が、CD70を発現する、実施形態1から22のいずれかに記載の方法。
［実施形態２４］対象に非フコシル化抗CD70抗体を投与することが、対象に非フコシル化抗CD70抗体を投与する前のがん細胞の量と比較して、少なくとも約5%、少なくとも約6%、少なくとも約7%、少なくとも約8%、少なくとも約9%、少なくとも約10%、少なくとも約15%、少なくとも約20%、少なくとも約25%、少なくとも約30%、少なくとも約35%、少なくとも約40%、少なくとも約45%、少なくとも約50%、少なくとも約60%、少なくとも約70%、少なくとも約80%、少なくとも約90%、少なくとも約95%又は約100%のがん細胞の枯渇をもたらす、実施形態1から23のいずれかに記載の方法。
［実施形態２５］対象に非フコシル化抗CD70抗体を投与することが、対象に脱フコシル化抗CD70抗体を投与する前のCD70+Tregの量と比較して、約20%、約10%、約9%、約8%、約7%、約6%、約5%、約4%、約3%、約2%、約1%又は約0.1%以下のCD70+Tregの枯渇をもたらす、実施形態1から24のいずれかに記載の方法。
［実施形態２６］ベースラインに対して、非フコシル化抗CD70抗体の投与後に対象において1つ以上の治療効果が改善される、実施形態1から25のいずれかに記載の方法。
［実施形態２７］1つ以上の治療効果が、客観的奏効率、応答の持続期間、応答までの期間、無増悪生存期間及び全生存期間からなる群から選択される、実施形態26に記載の方法。
［実施形態２８］客観的奏効率が、少なくとも約20%、少なくとも約25%、少なくとも約30%、少なくとも約35%、少なくとも約40%、少なくとも約45%、少なくとも約50%、少なくとも約60%、少なくとも約70%又は少なくとも約80%である、実施形態1から27のいずれかに記載の方法。
［実施形態２９］対象が、非フコシル化抗CD70抗体の投与後に少なくとも約1カ月、少なくとも約2カ月、少なくとも約3カ月、少なくとも約4カ月、少なくとも約5カ月、少なくとも約6カ月、少なくとも約7カ月、少なくとも約8カ月、少なくとも約9カ月、少なくとも約10カ月、少なくとも約11カ月、少なくとも約12カ月、少なくとも約18カ月、少なくとも約2年、少なくとも約3年、少なくとも約4年又は少なくとも約5年の無増悪生存期間を示す、実施形態1から28のいずれかに記載の方法。
［実施形態３０］対象が、非フコシル化抗CD70抗体の投与後に少なくとも約1カ月、少なくとも約2カ月、少なくとも約3カ月、少なくとも約4カ月、少なくとも約5カ月、少なくとも約6カ月、少なくとも約7カ月、少なくとも約8カ月、少なくとも約9カ月、少なくとも約10カ月、少なくとも約11カ月、少なくとも約12カ月、少なくとも約18カ月、少なくとも約2年、少なくとも約3年、少なくとも約4年又は少なくとも約5年の全生存期間を示す、実施形態1から29のいずれかに記載の方法。
［実施形態３１］抗CD70抗体に対する応答の持続期間が、非フコシル化抗CD70抗体の投与後に少なくとも約1カ月、少なくとも約2カ月、少なくとも約3カ月、少なくとも約4カ月、少なくとも約5カ月、少なくとも約6カ月、少なくとも約7カ月、少なくとも約8カ月、少なくとも約9カ月、少なくとも約10カ月、少なくとも約11カ月、少なくとも約12カ月、少なくとも約18カ月、少なくとも約2年、少なくとも約3年、少なくとも約4年又は少なくとも約5年である、実施形態1から30のいずれかに記載の方法。
［実施形態３２］抗CD70抗体の投与経路が静脈内である、実施形態1から31のいずれかに記載の方法。
［実施形態３３］対象がヒトである、実施形態1から32のいずれかに記載の方法。
［実施形態３４］抗CD70抗体が、アザシチジンと組み合わせて投与される、実施形態1から33のいずれかに記載の方法。
［実施形態３５］抗CD70抗体が、ベネトクラクスと組み合わせて投与される、実施形態1から33のいずれかに記載の方法。
［実施形態３６］抗CD70抗体が、アザシチジン及びベネトクラクスと組み合わせて投与される、実施形態1から33のいずれかに記載の方法。
［実施形態３７］抗CD70抗体が、フルオロキノロン（fluoroquinalone）と組み合わせて投与される、実施形態1から35のいずれかに記載の方法。
［実施形態３８］CD70発現がんの処置のための医薬組成物であって、非フコシル化抗CD70抗体と、少なくとも1つの薬学的に適合する成分とを含み、抗CD70抗体が、抗CD70抗体のCDRがKabat番号付けスキームによって規定される、配列番号1の3つのCDRを含む重鎖可変領域、配列番号2の3つのCDRを含む軽鎖可変領域及びFcドメインを含み、前記組成物が、実施形態1から37のいずれかに記載の方法における使用のためのものである、医薬組成物。
［実施形態３９］非フコシル化抗CD70抗体と、実施形態1から37のいずれかに記載の方法において抗CD70抗体を使用するための使用説明書とを含むキットであって、抗CD70抗体が、抗CD70抗体のCDRがKabat番号付けスキームによって規定される、配列番号1の3つのCDRを含む重鎖可変領域、配列番号2の3つのCDRを含む軽鎖可変領域及びFcドメインを含む、キット。
The invention will be more fully understood by reference to the following examples. However, they should not be construed as limiting the scope of the invention. The examples and embodiments described herein are for illustrative purposes only, and various modifications or changes may be suggested to those skilled in the art in light of the same and within the spirit and scope of this application and the appended claims. It is understood that it should be included within.
For example, the invention encompasses the following embodiments:
[Embodiment 1] A method of treating a CD70-expressing cancer in a subject, the method comprising administering to the subject a therapeutically effective amount of a non-fucosylated anti-CD70 antibody, said method causing depletion of cancer cells in the subject. and does not result in depletion of CD70+ regulatory T cells (CD70+ Tregs) in the subject, and the anti-CD70 antibody is a heavy antibody containing three CDRs of SEQ ID NO: 1, where the CDRs of the anti-CD70 antibody are defined by the Kabat numbering scheme. a chain variable region, a light chain variable region comprising the three CDRs of SEQ ID NO: 2, and an Fc domain, wherein the cancer is selected from the group consisting of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). .
[Embodiment 2] An anti-CD70 antibody has a heavy chain variable region comprising an amino acid sequence that is at least 85% identical to the amino acid sequence of SEQ ID NO: 1 and an amino acid sequence that is at least 85% identical to the amino acid sequence of SEQ ID NO: 2. 2. The method of embodiment 1, comprising a light chain variable region comprising:
[Embodiment 3] The method according to Embodiment 1, wherein the anti-CD70 antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 1 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 2.
[Embodiment 4] The Fc domain is an antibody effector domain that mediates one or more of antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and complement-dependent cellular cytotoxicity (CDC), The method according to any of embodiments 1-3.
[Embodiment 5] The method according to any one of Embodiments 1 to 3, wherein the Fc domain is an antibody effector domain that mediates ADCC.
[Embodiment 6] The method according to any one of Embodiments 1 to 5, wherein the Fc domain is a human Fc domain.
[Embodiment 7] The method according to any one of Embodiments 1 to 6, wherein the anti-CD70 antibody is borcetuzumab.
[Embodiment 8] The method of any of embodiments 1 to 7, wherein the antibody is conjugated to a therapeutic agent.
[Embodiment 9] The method according to Embodiment 8, wherein the therapeutic agent is a chemotherapeutic agent or an immunomodulator.
[Embodiment 10] The method according to Embodiment 8, wherein the therapeutic agent is a chemotherapeutic agent.
[Embodiment 11] The method according to Embodiment 10, wherein the chemotherapeutic agent is monomethyl auristatin E (MMAE) or monomethyl auristatin F (MMAF).
[Embodiment 12] The method of embodiment 8, wherein the therapeutic agent is an immunomodulator.
[Embodiment 13] The method comprises administering a population of anti-CD70 antibodies, each antibody in the population of anti-CD70 antibodies having a CDR of SEQ ID NO: 1, wherein the CDRs of the anti-CD70 antibody are defined by the Kabat numbering scheme. A heavy chain variable region comprising three CDRs, a light chain variable region comprising three CDRs of SEQ ID NO: 2, and an Fc domain, and at least 50% of the anti-CD70 antibodies in the population of anti-CD70 antibodies lack core fucosylation. The method according to any of Forms 1 to 12.
[Embodiment 14] The method of embodiment 13, wherein at least 70% of the anti-CD70 antibodies in the population of anti-CD70 antibodies lack core fucosylation.
[Embodiment 15] The method of embodiment 13, wherein at least 90% of the anti-CD70 antibodies in the population of anti-CD70 antibodies lack core fucosylation.
[Embodiment 16] The method according to any one of Embodiments 1 to 15, wherein the cancer is MDS.
[Embodiment 17] The method according to Embodiment 16, wherein the MDS is relapsed or refractory MDS.
[Embodiment 18] The method of embodiment 17, wherein the subject experienced treatment failure after previous hypomethylating agent (HMA) therapy for MDS.
[Embodiment 19] The method according to any one of Embodiments 1 to 15, wherein the cancer is AML.
[Embodiment 20] The method according to Embodiment 19, wherein the AML is relapsed or refractory AML.
[Embodiment 21] The method of embodiment 20, wherein the subject has received two previous treatment regimens to treat AML.
[Embodiment 22] The method of embodiment 20, wherein the subject has received three previous treatment regimens to treat AML.
[Embodiment 23] At least about 0.1%, at least about 1%, at least about 2%, at least about 3%, at least about 4%, at least about 5%, at least about 6%, at least about 7%, at least about 8%, at least about 9%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least 23. The method of any of embodiments 1-22, wherein about 50%, at least about 60%, at least about 70% or at least about 80% express CD70.
[Embodiment 24] Administering the non-fucosylated anti-CD70 antibody to the subject results in a reduction in the amount of cancer cells of at least about 5%, at least about 6% compared to the amount of cancer cells before administering the non-fucosylated anti-CD70 antibody to the subject. %, at least about 7%, at least about 8%, at least about 9%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40 %, at least about 45%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, at least about 95% or about 100% depletion of cancer cells. The method according to any of Forms 1 to 23.
[Embodiment 25] Administering the non-fucosylated anti-CD70 antibody to the subject reduces the amount of CD70+ Tregs by about 20%, about 10%, compared to the amount of CD70+ Tregs before administering the defucosylated anti-CD70 antibody to the subject. Implementation that results in depletion of CD70+ Tregs of less than about 9%, about 8%, about 7%, about 6%, about 5%, about 4%, about 3%, about 2%, about 1%, or about 0.1% The method according to any of Forms 1 to 24.
[Embodiment 26] The method of any of embodiments 1-25, wherein one or more therapeutic effects are improved in the subject after administration of the non-fucosylated anti-CD70 antibody relative to baseline.
[Embodiment 27] The method according to embodiment 26, wherein the one or more therapeutic effects are selected from the group consisting of objective response rate, duration of response, time to response, progression-free survival, and overall survival. Method.
[Embodiment 28] The objective response rate is at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%. , at least about 70% or at least about 80%.
[Embodiment 29] The subject is at least about 1 month, at least about 2 months, at least about 3 months, at least about 4 months, at least about 5 months, at least about 6 months, at least about 7 months after administration of the non-fucosylated anti-CD70 antibody. at least about 8 months, at least about 9 months, at least about 10 months, at least about 11 months, at least about 12 months, at least about 18 months, at least about 2 years, at least about 3 years, at least about 4 years, or at least about 5 29. The method of any of embodiments 1-28, showing progression free survival in years.
[Embodiment 30] The subject is at least about 1 month, at least about 2 months, at least about 3 months, at least about 4 months, at least about 5 months, at least about 6 months, at least about 7 months after administration of the non-fucosylated anti-CD70 antibody. at least about 8 months, at least about 9 months, at least about 10 months, at least about 11 months, at least about 12 months, at least about 18 months, at least about 2 years, at least about 3 years, at least about 4 years, or at least about 5 30. The method of any of embodiments 1-29, showing overall survival in years.
[Embodiment 31] The duration of the response to the anti-CD70 antibody is at least about 1 month, at least about 2 months, at least about 3 months, at least about 4 months, at least about 5 months, at least about 6 months, at least about 7 months, at least about 8 months, at least about 9 months, at least about 10 months, at least about 11 months, at least about 12 months, at least about 18 months, at least about 2 years, at least about 3 years, at least 31. The method of any of embodiments 1-30, wherein the method is about 4 years or at least about 5 years.
[Embodiment 32] The method according to any one of Embodiments 1 to 31, wherein the administration route of the anti-CD70 antibody is intravenous.
[Embodiment 33] The method according to any one of Embodiments 1 to 32, wherein the subject is a human.
[Embodiment 34] The method according to any of embodiments 1 to 33, wherein the anti-CD70 antibody is administered in combination with azacytidine.
[Embodiment 35] The method of any of embodiments 1 to 33, wherein the anti-CD70 antibody is administered in combination with venetoclax.
[Embodiment 36] The method of any of embodiments 1 to 33, wherein the anti-CD70 antibody is administered in combination with azacytidine and venetoclax.
[Embodiment 37] The method of any of embodiments 1 to 35, wherein the anti-CD70 antibody is administered in combination with a fluoroquinolone.
[Embodiment 38] A pharmaceutical composition for the treatment of CD70-expressing cancer, comprising a non-fucosylated anti-CD70 antibody and at least one pharmaceutically compatible component, wherein the anti-CD70 antibody is an anti-CD70 antibody. The composition comprises a heavy chain variable region comprising the three CDRs of SEQ ID NO: 1, a light chain variable region comprising the three CDRs of SEQ ID NO: 2, and an Fc domain, the CDRs of which are defined by the Kabat numbering scheme, 38. A pharmaceutical composition for use in the method of any of embodiments 1-37.
[Embodiment 39] A kit comprising a non-fucosylated anti-CD70 antibody and instructions for using the anti-CD70 antibody in the method of any of embodiments 1 to 37, wherein the anti-CD70 antibody comprises: A kit comprising a heavy chain variable region comprising three CDRs of SEQ ID NO: 1, a light chain variable region comprising three CDRs of SEQ ID NO: 2, and an Fc domain, wherein the CDRs of an anti-CD70 antibody are defined by the Kabat numbering scheme.
Claims (31)
（ii）抗CD70抗体が、ベネトクラクスと組み合わせて投与される、
（iii）抗CD70抗体が、アザシチジン及びベネトクラクスと組み合わせて投与される、
（iv）抗CD70抗体が、フルオロキノロン（fluoroquinalone）と組み合わせて投与される、
（v）抗CD70抗体が、アザシチジン及びフルオロキノロンと組み合わせて投与される、
（vi）抗CD70抗体が、ベネトクラクス及びフルオロキノロンと組み合わせて投与される、あるいは
（vii）抗CD70抗体が、アザシチジン、ベネトクラクス及びフルオロキノロンと組み合わせて投与される、
請求項1から28のいずれか一項に記載の組成物。 (i) the anti-CD70 antibody is administered in combination with azacytidine;
(ii) the anti-CD70 antibody is administered in combination with venetoclax;
(iii) the anti-CD70 antibody is administered in combination with azacytidine and venetoclax;
(iv) the anti-CD70 antibody is administered in combination with a fluoroquinolone;
(v) the anti-CD70 antibody is administered in combination with azacytidine and a fluoroquinolone;
(vi) the anti-CD70 antibody is administered in combination with venetoclax and a fluoroquinolone; or
(vii) the anti-CD70 antibody is administered in combination with azacitidine, venetoclax and a fluoroquinolone;
29. A composition according to any one of claims 1 to 28 .
30. A kit comprising a non-fucosylated anti-CD70 antibody and instructions for using the composition according to any one of claims 1 to 29 , wherein the anti-CD70 antibody has a CDR of the anti-CD70 antibody. A kit comprising a heavy chain variable region comprising the three CDRs of SEQ ID NO: 1, a light chain variable region comprising the three CDRs of SEQ ID NO: 2, and an Fc domain, as defined by the Kabat numbering scheme.
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| US63/011,906 | 2020-04-17 | ||
| PCT/US2020/067173 WO2021138264A1 (en) | 2019-12-30 | 2020-12-28 | Methods of treating cancer with nonfucosylated anti-cd70 antibodies |
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| GB2487551A (en) | 2011-01-26 | 2012-08-01 | Rolls Royce Plc | Coupling having a threaded interconnector to limit torque |
| US10196445B1 (en) | 2015-03-17 | 2019-02-05 | Bristol-Myers Squibb Company | Ipilimumab variant with enhanced ADCC |
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2020
- 2020-12-25 TW TW109146217A patent/TW202138388A/en unknown
- 2020-12-28 US US17/134,963 patent/US11820827B2/en active Active
- 2020-12-28 AU AU2020416193A patent/AU2020416193A1/en active Pending
- 2020-12-28 MX MX2022007974A patent/MX2022007974A/en unknown
- 2020-12-28 KR KR1020227026079A patent/KR20220133889A/en unknown
- 2020-12-28 EP EP20845735.8A patent/EP4085073A1/en active Pending
- 2020-12-28 CN CN202080097661.4A patent/CN115605509A/en active Pending
- 2020-12-28 IL IL294262A patent/IL294262A/en unknown
- 2020-12-28 JP JP2022539657A patent/JP2023508496A/en active Pending
- 2020-12-28 WO PCT/US2020/067173 patent/WO2021138264A1/en unknown
- 2020-12-28 BR BR112022012885A patent/BR112022012885A2/en unknown
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