JPWO2021141977A5 - - Google Patents
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- JPWO2021141977A5 JPWO2021141977A5 JP2022541785A JP2022541785A JPWO2021141977A5 JP WO2021141977 A5 JPWO2021141977 A5 JP WO2021141977A5 JP 2022541785 A JP2022541785 A JP 2022541785A JP 2022541785 A JP2022541785 A JP 2022541785A JP WO2021141977 A5 JPWO2021141977 A5 JP WO2021141977A5
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Description
[本発明1001]
メチルチオアデノシンホスホリラーゼ活性を有するポリペプチドを含む組成物であって、該ポリペプチドの少なくとも1つのアミノ酸残基が、コンジュゲーション部位を排除するように操作されている、前記組成物。
[本発明1002]
ポリペプチドが、SEQ ID NO: 1の少なくとも100個の連続するアミノ酸と少なくとも80%の配列同一性を有するアミノ酸配列を含み、かつ、SEQ ID NO: 1のトレオニン18、トレオニン197、セリン178、バリン233およびメチオニン196に対応するアミノ酸を含む、本発明1001の組成物。
[本発明1003]
ポリペプチドの前記少なくとも1つのアミノ酸残基が、第1のリジンまたは第1のシステインを含む、本発明1001の組成物。
[本発明1004]
SEQ ID NO: 1のリジン225に対応するアミノ酸が、コンジュゲーション部位を排除するように操作されている、本発明1002のいずれかの組成物。
[本発明1005]
SEQ ID NO: 1のリジン238に対応するアミノ酸が、コンジュゲーション部位を排除するように操作されている、本発明1002のいずれかの組成物。
[本発明1006]
リジン225に対応するアミノ酸またはリジン238に対応するアミノ酸が、アルギニンで置換されている、本発明1004または1005の組成物。
[本発明1007]
メチルチオアデノシンのメチルチオリボースリン酸およびアデニンへの加リン酸分解に対するポリペプチドのK cat /K m が、少なくとも1.5×10 5 M -1 s -1 である、本発明1001～1006のいずれかの組成物。
[本発明1008]
メチルチオアデノシンのメチルチオリボースリン酸およびアデニンへの加リン酸分解に対するポリペプチドのK cat /K m が、約1.5×10 5 M -1 s -1 ～3.0×10 5 M -1 s -1 である、本発明1001～1006のいずれかの組成物。
[本発明1009]
メチルチオアデノシンのメチルチオリボースリン酸およびアデニンへの加リン酸分解に対するポリペプチドのK cat /K m が、SEQ ID NO: 1を含むメチルチオアデノシンホスホリラーゼのV max の少なくとも50%である、本発明1001～1006のいずれかの組成物。
[本発明1010]
メチルチオアデノシンのメチルチオリボースリン酸およびアデニンへの加リン酸分解に対するポリペプチドのV max が、SEQ ID NO: 1を含むメチルチオアデノシンホスホリラーゼのV max の少なくとも50%である、本発明1001～1006のいずれかの組成物。
[本発明1011]
メチルチオアデノシンのメチルチオリボースリン酸およびアデニンへの加リン酸分解に対するポリペプチドのK m が、SEQ ID NO: 1を含むメチルチオアデノシンホスホリラーゼのK m の2倍以下である、本発明1001～1006のいずれかの組成物。
[本発明1012]
本発明1001～1008のいずれかのポリペプチドにコンジュゲートされた少なくとも1つの重合体を含む組成物であって、該重合体が、該ポリペプチドの血清中半減期を、コンジュゲートされていないポリペプチドと比較して増加させる、前記組成物。
[本発明1013]
少なくとも1つの重合体が、ポリエチレングリコールである、本発明1012の組成物。
[本発明1014]
ポリエチレングリコールが、約5000 kDaの平均分子量を有する、本発明1013の組成物。
[本発明1015]
ポリエチレングリコールが、約500 kDa～約1000 kDa、約800 kDa～約1600 kDa、約1500 kDa～約3000 kDa、約2000 kDa～約4000 kDa、約2500 kDa～約5000 kDa、約3000 kDa～約6000 kDa、約4,000 kDa～約8,000 kDa、約6,000 kDa～約12,000 kDa、約10,000 kDa～約20,000 kDa、または約15,000 kDa～約30,000 kDaの平均分子量を有する、本発明1013の組成物。
[本発明1016]
少なくとも1つの重合体が、ポリペプチドの第2のリジンまたは第2のシステインにコンジュゲートされている、本発明1014または1015の組成物。
[本発明1017]
本発明1001～1016のいずれかのポリペプチドの集団を含む組成物であって、該集団が該ポリペプチドの三量体を含む、前記組成物。
[本発明1018]
本発明1001～1017のいずれかのポリペプチドの集団を含む組成物であって、該ポリペプチドの少なくとも80%が前記少なくとも1つの重合体を含む、前記組成物。
[本発明1019]
ポリペプチドの少なくとも80%が、前記少なくとも1つの重合体の少なくとも3つを含む、本発明1018の組成物。
[本発明1020]
ポリペプチドの少なくとも80%が、前記少なくとも1つの重合体の少なくとも6つを含む、本発明1019の組成物。
[本発明1021]
ポリペプチド当たりの重合体の数が、ガウス分布を含む、本発明1018～1020のいずれかの組成物。
[本発明1022]
ガウス分布が、ポリペプチド当たり2±1、3±1、4±1、または6±1個の重合体の最頻値(mode)を有する、本発明1021の組成物。
[本発明1023]
ガウス分布が、ポリペプチド当たり8±3個の重合体の最頻値を有する、本発明1021の組成物。
[本発明1024]
メチルチオアデノシンのメチルチオリボースリン酸およびアデニンへの加リン酸分解に対するポリペプチドのK cat /K m が、少なくとも1.5×10 5 M -1 s -1 である、本発明1012～1021のいずれかの組成物。
[本発明1025]
メチルチオアデノシンのメチルチオリボースリン酸およびアデニンへの加リン酸分解に対するポリペプチドのK cat /K m が、約1.5×10 5 M -1 s -1 ～3.0×10 5 M -1 s -1 である、本発明1012～1021のいずれかの組成物。
[本発明1026]
メチルチオアデノシンのメチルチオリボースリン酸およびアデニンへの加リン酸分解に対するポリペプチドのK cat /K m が、SEQ ID NO: 1を含むメチルチオアデノシンホスホリラーゼのV max の少なくとも50%である、本発明1012～1021のいずれかの組成物。
[本発明1027]
ポリペプチドのメチルチオアデノシンホスホリラーゼ活性のV max が、SEQ ID NO: 1を含むメチルチオアデノシンホスホリラーゼのメチルチオアデノシンホスホリラーゼ活性のV max の少なくとも50%である、本発明1012～1021のいずれかの組成物。
[本発明1028]
ポリペプチドのメチルチオアデノシンホスホリラーゼ活性のK m が、SEQ ID NO: 1を含むメチルチオアデノシンホスホリラーゼのメチルチオアデノシンホスホリラーゼ活性のK m の2倍以下である、本発明1012～1021のいずれかの組成物。
[本発明1029]
異種ペプチドセグメントをさらに含む、本発明1001～1028のいずれかの組成物。
[本発明1030]
異種ペプチドセグメントが、ターゲティング部分を含む、本発明1029の組成物。
[本発明1031]
ターゲティング部分が、抗体もしくはその断片、またはペプチドを含む、本発明1027の組成物。
[本発明1032]
本発明1001～1031のいずれかのポリペプチドをコードするヌクレオチド配列を含む、核酸。
[本発明1033]
細菌、真菌、昆虫、または哺乳動物における発現のためにコドン最適化されている、本発明1032の核酸。
[本発明1034]
細菌における発現のためにコドン最適化されている、本発明1033の核酸。
[本発明1035]
細菌が大腸菌(E. coli)である、本発明1034の核酸。
[本発明1036]
SEQ ID NO: 4および6のうちの1つに記載の配列を含む、本発明1032の核酸。
[本発明1037]
本発明1032～1035のいずれかの核酸を含む、発現ベクター。
[本発明1038]
本発明1032～1036のいずれかの核酸を含む、宿主細胞。
[本発明1039]
細菌細胞、真菌細胞、昆虫細胞、または哺乳動物細胞である、本発明1038の宿主細胞。
[本発明1040]
細菌細胞が大腸菌細胞である、本発明1039の宿主細胞。
[本発明1041]
薬学的に許容される担体中に本発明1001～1040のいずれかの組成物を含む、薬学的製剤。
[本発明1042]
以下の段階を含む、腫瘍を有する患者を処置する方法：
メチルチオアデノシンホスホリラーゼ活性を有するポリペプチドを含む組成物の有効量を該患者に投与する段階であって、該ポリペプチドが、少なくとも36時間の血清中半減期を有する、段階。
[本発明1043]
組成物が本発明1041の薬学的製剤である、本発明1042の方法。
[本発明1044]
患者が以前、腫瘍と診断された、本発明1042または1043の方法。
[本発明1045]
患者が固形腫瘍を有する、本発明1042または1043の方法。
[本発明1046]
腫瘍が血液学的腫瘍を含む、本発明1042または1043の方法。
[本発明1047]
腫瘍が黒色腫を含む、本発明1042または1043の方法。
[本発明1048]
腫瘍が乳がんを含む、本発明1042または1043の方法。
[本発明1049]
腫瘍が結腸がんを含む、本発明1042または1043の方法。
[本発明1050]
腫瘍が骨肉腫、膵臓がん、脊索腫、中皮腫、T細胞ALL、神経膠腫、腎細胞がん、黒色腫、扁平上皮がん、胆嚢がん、胃がん、または肝細胞がんを含む、本発明1042または1043の方法。
[本発明1051]
腫瘍がMTAP欠失を有する、本発明1042の方法。
[本発明1052]
腫瘍が、参照レベルと比べて減少したレベルのメチルチオアデノシンホスホリラーゼポリペプチドを有する、本発明1042～1051のいずれかの方法。
[本発明1053]
腫瘍が、参照レベルと比べて減少したレベルのメチルチオアデノシンホスホリラーゼ活性を有する、本発明1042～1051のいずれかの方法。
[本発明1054]
腫瘍が、参照レベルと比べて増加したレベルのCD73を有する、本発明1042～1051のいずれかの方法。
[本発明1055]
腫瘍が、参照レベルと比べて増加したレベルのCD39を有する、本発明1042～1051のいずれかの方法。
[本発明1056]
腫瘍が、参照レベルと比べて増加したレベルのMTAを有する、本発明1042～1051のいずれかの方法。
[本発明1057]
腫瘍が、参照レベルと比べて増加したレベルのADOを有する、本発明1042～1051のいずれかの方法。
[本発明1058]
参照レベルが、健常対象におけるレベルである、本発明1052～1057のいずれかの方法。
[本発明1059]
参照レベルが、患者の健常組織におけるレベルである、本発明1052～1057のいずれかの方法。
[本発明1060]
患者がヒト患者である、本発明1042～1059のいずれかの方法。
[本発明1061]
製剤が、腫瘍内に、静脈内に、皮内に、動脈内に、腹腔内に、病巣内に、頭蓋内に、関節内に、前立腺内に、胸膜内に、気管内に、眼内に、鼻腔内に、硝子体内に、膣内に、直腸内に、筋肉内に、皮下に、結膜下に、小胞内に、粘膜に、心膜内に、臍帯内に、経口的に、吸入により、注射により、注入により、持続注入により、標的細胞を直接浸す局所灌流により、カテーテルによって、または洗浄によって投与される、本発明1042～1060のいずれかの方法。
[本発明1062]
薬学的組成物が、免疫療法に対する感受性を増加させる、本発明1042～1061のいずれかの方法。
[本発明1063]
患者が以前、免疫チェックポイント阻害剤の投与に応答することができなかった、本発明1062の方法。
[本発明1064]
対象に少なくとも第2の抗がん療法を施す段階をさらに含む、本発明1042～1063のいずれかの方法。
[本発明1065]
第2の抗がん療法が、外科療法、化学療法、放射線療法、凍結療法、ホルモン療法、免疫療法、またはサイトカイン療法を含む、本発明1064の方法。
[本発明1066]
第2の抗がん療法が、免疫チェックポイント阻害剤を含む、本発明1064の方法。
[本発明1067]
免疫チェックポイント阻害剤が、抗PD-L1抗体を含む、本発明1066の方法。
[本発明1068]
抗PD-L1抗体が、アテゾリズマブ、アベルマブ、デュルバルマブ、BMS-036559、またはCK-301を含む、本発明1067の方法。
[本発明1069]
免疫チェックポイント阻害剤が、抗PD1抗体を含む、本発明1066の方法。
[本発明1070]
抗PD1抗体が、ニボルマブ、ペムブロリズマブ、ピディリズマブ、AMP-223、AMP-514、セミプリマブ、またはPDR-001を含む、本発明1069の方法。
[本発明1071]
免疫チェックポイント阻害剤が、抗CTLA-4抗体を含む、本発明1066の方法。
[本発明1072]
抗CTLA-4療法が、イピリムマブまたはトレメリムマブを含む、本発明1071の方法。
[本発明1073]
第2の抗がん療法が、養子T細胞療法を含む、本発明1066の方法。
[本発明1074]
養子T細胞療法が、MTAP酵素の投与に続いて施される、本発明1074の方法。
[本発明1075]
以下の段階を含む、腫瘍を有する患者を処置する方法：
MTAP酵素を発現するように操作されているT細胞を含む養子T細胞療法を該患者に施す段階。
[本発明1076]
がんの転移が遅延、低減、または抑止される、本発明1042～1075のいずれかの方法。
[本発明1077]
腫瘍を有する患者への治療適用のための医薬の製造のための、本発明1001～1031のいずれかのMTAP酵素、本発明1032～1036のいずれかの核酸、または本発明1041の薬学的組成物の使用。
本発明の他の目的、特徴および利点は、以下の詳細な説明から明らかになるであろう。しかしながら、詳細な説明および具体例は、本発明の好ましい態様を示しているが、例示としてのみ与えられていることを理解すべきである。というのは、本発明の趣旨および範囲内のさまざまな変更および修飾がこの詳細な説明から当業者には明らかになるからである。
[Invention 1001]
A composition comprising a polypeptide having methylthioadenosine phosphorylase activity, wherein at least one amino acid residue of the polypeptide has been engineered to exclude a conjugation site.
[Present invention 1002]
the polypeptide comprises an amino acid sequence having at least 80% sequence identity with at least 100 contiguous amino acids of SEQ ID NO: 1, and threonine 18, threonine 197, serine 178, valine of SEQ ID NO: 1; The composition of the invention 1001, comprising amino acids corresponding to 233 and methionine 196.
[Present invention 1003]
The composition of the invention 1001, wherein said at least one amino acid residue of the polypeptide comprises a first lysine or a first cysteine.
[Present invention 1004]
Any composition of the invention 1002, wherein the amino acid corresponding to lysine 225 of SEQ ID NO: 1 has been engineered to eliminate the conjugation site.
[Present invention 1005]
Any composition of the invention 1002, wherein the amino acid corresponding to lysine 238 of SEQ ID NO: 1 has been engineered to eliminate the conjugation site.
[Present invention 1006]
The composition of the present invention 1004 or 1005, wherein the amino acid corresponding to lysine 225 or the amino acid corresponding to lysine 238 is substituted with arginine.
[Present invention 1007]
The composition of any of the inventions 1001 to 1006, wherein the polypeptide has a K cat /K m for phosphorolysis of methylthioadenosine to methylthiolibose phosphate and adenine of at least 1.5×10 5 M −1 s −1 thing.
[Present invention 1008]
The K cat /K m of the polypeptide for phosphorolysis of methylthioadenosine to methylthiolibose phosphate and adenine is about 1.5×10 5 M −1 s −1 to 3.0×10 5 M −1 s −1 , the composition according to any one of the present inventions 1001 to 1006.
[Present invention 1009]
Invention 1001-, wherein the K cat /K m of the polypeptide for phosphorolysis of methylthioadenosine to methylthiolibose phosphate and adenine is at least 50% of the V max of methylthioadenosine phosphorylase comprising SEQ ID NO: 1. Any composition of 1006.
[Present invention 1010]
Any of the inventions 1001-1006, wherein the V max of the polypeptide for phosphorolysis of methylthioadenosine to methylthiolibose phosphate and adenine is at least 50% of the V max of methylthioadenosine phosphorylase comprising SEQ ID NO: 1. composition.
[Present invention 1011]
Any of the inventions 1001 to 1006, wherein the K m of the polypeptide for phosphorolysis of methylthioadenosine to methylthiolibose phosphate and adenine is less than or equal to twice the K m of methylthioadenosine phosphorylase comprising SEQ ID NO: 1. composition.
[Invention 1012]
A composition comprising at least one polymer conjugated to a polypeptide of any of the inventions 1001-1008, wherein the polymer reduces the serum half-life of the polypeptide to an unconjugated polypeptide. said composition increasing compared to a peptide.
[Present invention 1013]
The composition of this invention 1012, wherein at least one polymer is polyethylene glycol.
[Present invention 1014]
The composition of the invention 1013, wherein the polyethylene glycol has an average molecular weight of about 5000 kDa.
[Present invention 1015]
Polyethylene glycol is about 500 kDa to about 1000 kDa, about 800 kDa to about 1600 kDa, about 1500 kDa to about 3000 kDa, about 2000 kDa to about 4000 kDa, about 2500 kDa to about 5000 kDa, about 3000 kDa to about 6000 kDa A composition of the invention 1013 having an average molecular weight of kDa, about 4,000 kDa to about 8,000 kDa, about 6,000 kDa to about 12,000 kDa, about 10,000 kDa to about 20,000 kDa, or about 15,000 kDa to about 30,000 kDa.
[Invention 1016]
The composition of the invention 1014 or 1015, wherein the at least one polymer is conjugated to a second lysine or a second cysteine of the polypeptide.
[Invention 1017]
A composition comprising a population of the polypeptides of any of the invention 1001-1016, wherein said population comprises trimers of said polypeptides.
[Invention 1018]
A composition comprising a population of polypeptides of any of the invention 1001-1017, wherein at least 80% of said polypeptides comprises said at least one polymer.
[Invention 1019]
1018. The composition of the invention, wherein at least 80% of the polypeptide comprises at least three of said at least one polymer.
[Invention 1020]
The composition of the invention 1019, wherein at least 80% of the polypeptide comprises at least 6 of said at least one polymer.
[Invention 1021]
The composition of any of the inventions 1018-1020, wherein the number of polymers per polypeptide comprises a Gaussian distribution.
[Invention 1022]
The composition of the invention 1021, wherein the Gaussian distribution has a mode of 2±1, 3±1, 4±1, or 6±1 polymers per polypeptide.
[Invention 1023]
The composition of the invention 1021, wherein the Gaussian distribution has a mode of 8±3 polymers per polypeptide.
[Invention 1024]
The composition of any of the inventions 1012-1021, wherein the polypeptide has a K cat /K m for phosphorolysis of methylthioadenosine to methylthiolibose phosphate and adenine of at least 1.5×10 5 M −1 s −1 thing.
[Invention 1025]
The K cat /K m of the polypeptide for phosphorolysis of methylthioadenosine to methylthiolibose phosphate and adenine is about 1.5×10 5 M −1 s −1 to 3.0×10 5 M −1 s −1 , the composition according to any one of Inventions 1012 to 1021.
[Invention 1026]
Invention 1012-, wherein the K cat /K m of the polypeptide for phosphorolysis of methylthioadenosine to methylthiolibose phosphate and adenine is at least 50% of the V max of methylthioadenosine phosphorylase comprising SEQ ID NO: 1. Any composition of 1021.
[Invention 1027]
The composition of any of the inventions 1012-1021, wherein the V max of methylthioadenosine phosphorylase activity of the polypeptide is at least 50% of the V max of methylthioadenosine phosphorylase activity of the methylthioadenosine phosphorylase comprising SEQ ID NO: 1 .
[Invention 1028]
The composition of any of the inventions 1012 to 1021, wherein the K m of the methylthioadenosine phosphorylase activity of the polypeptide is less than or equal to twice the K m of the methylthioadenosine phosphorylase activity of the methylthioadenosine phosphorylase comprising SEQ ID NO: 1 .
[Invention 1029]
The composition of any of the inventions 1001-1028, further comprising a heterologous peptide segment.
[Invention 1030]
A composition of the invention 1029, wherein the heterologous peptide segment comprises a targeting moiety.
[Present invention 1031]
1027. The composition of the invention, wherein the targeting moiety comprises an antibody or fragment thereof, or a peptide.
[Invention 1032]
A nucleic acid comprising a nucleotide sequence encoding any of the polypeptides of the present invention 1001-1031.
[Present invention 1033]
Nucleic acids of the invention 1032 that are codon-optimized for expression in bacteria, fungi, insects, or mammals.
[Present invention 1034]
Nucleic acids of the invention 1033 that are codon-optimized for expression in bacteria.
[Invention 1035]
The nucleic acid of the present invention 1034, wherein the bacterium is E. coli.
[Invention 1036]
A nucleic acid according to the invention 1032, comprising a sequence according to one of SEQ ID NO: 4 and 6.
[Present invention 1037]
An expression vector comprising any of the nucleic acids of the present invention 1032 to 1035.
[Invention 1038]
A host cell comprising any of the nucleic acids of the present invention 1032-1036.
[Invention 1039]
The host cell of the invention 1038 is a bacterial cell, fungal cell, insect cell, or mammalian cell.
[Invention 1040]
The host cell of the invention 1039, wherein the bacterial cell is an E. coli cell.
[Present invention 1041]
A pharmaceutical formulation comprising any of the compositions of the invention 1001-1040 in a pharmaceutically acceptable carrier.
[Invention 1042]
A method of treating a patient with a tumor, including the following steps:
administering to the patient an effective amount of a composition comprising a polypeptide having methylthioadenosine phosphorylase activity, wherein the polypeptide has a serum half-life of at least 36 hours.
[Invention 1043]
The method of this invention 1042, wherein the composition is a pharmaceutical formulation of this invention 1041.
[Present invention 1044]
The method of the invention 1042 or 1043, wherein the patient was previously diagnosed with a tumor.
[Invention 1045]
1043. The method of the invention 1042 or 1043, wherein the patient has a solid tumor.
[Invention 1046]
The method of the invention 1042 or 1043, wherein the tumor comprises a hematological tumor.
[Invention 1047]
The method of the invention 1042 or 1043, wherein the tumor comprises melanoma.
[Invention 1048]
The method of the invention 1042 or 1043, wherein the tumor comprises breast cancer.
[Invention 1049]
The method of the invention 1042 or 1043, wherein the tumor comprises colon cancer.
[Invention 1050]
The tumor includes osteosarcoma, pancreatic cancer, chordoma, mesothelioma, T-cell ALL, glioma, renal cell carcinoma, melanoma, squamous cell carcinoma, gallbladder cancer, gastric cancer, or hepatocellular carcinoma , the method of the invention 1042 or 1043.
[Present invention 1051]
1042. The method of the invention 1042, wherein the tumor has an MTAP deletion.
[Invention 1052]
The method of any of the inventions 1042-1051, wherein the tumor has a decreased level of methylthioadenosine phosphorylase polypeptide compared to a reference level.
[Present invention 1053]
The method of any of the inventions 1042-1051, wherein the tumor has a decreased level of methylthioadenosine phosphorylase activity compared to a reference level.
[Invention 1054]
The method of any of the inventions 1042-1051, wherein the tumor has an increased level of CD73 compared to a reference level.
[Present invention 1055]
The method of any of the inventions 1042-1051, wherein the tumor has an increased level of CD39 compared to a reference level.
[Invention 1056]
The method of any of the inventions 1042-1051, wherein the tumor has an increased level of MTA compared to a reference level.
[Present invention 1057]
The method of any of the inventions 1042-1051, wherein the tumor has an increased level of ADO compared to a reference level.
[Invention 1058]
The method of any of the inventions 1052-1057, wherein the reference level is a level in a healthy subject.
[Invention 1059]
The method of any of the inventions 1052-1057, wherein the reference level is a level in healthy tissue of the patient.
[Invention 1060]
The method of any of the inventions 1042-1059, wherein the patient is a human patient.
[Present invention 1061]
The preparation may be administered intratumorally, intravenously, intradermally, intraarterially, intraperitoneally, intralesionally, intracranially, intraarticularly, prostatically, intrapleurally, intratracheally, intraocularly. , intranasally, intravitreally, vaginally, rectally, intramuscularly, subcutaneously, subconjunctivally, intravesicularly, mucosally, intrapericardially, intraumbilically, orally, by inhalation. The method of any of the inventions 1042-1060, wherein the method is administered by injection, by infusion, by continuous infusion, by local perfusion directly bathing the target cells, by catheter, or by lavage.
[Invention 1062]
The method of any of the inventions 1042-1061, wherein the pharmaceutical composition increases susceptibility to immunotherapy.
[Invention 1063]
1062. The method of the invention 1062, wherein the patient has previously failed to respond to administration of an immune checkpoint inhibitor.
[Invention 1064]
The method of any of the inventions 1042-1063, further comprising administering at least a second anti-cancer therapy to the subject.
[Invention 1065]
1064. The method of the invention 1064, wherein the second anti-cancer therapy comprises surgical therapy, chemotherapy, radiation therapy, cryotherapy, hormonal therapy, immunotherapy, or cytokine therapy.
[Invention 1066]
1064. The method of the invention, wherein the second anti-cancer therapy comprises an immune checkpoint inhibitor.
[Invention 1067]
1066. The method of the invention, wherein the immune checkpoint inhibitor comprises an anti-PD-L1 antibody.
[Invention 1068]
1067. The method of the invention 1067, wherein the anti-PD-L1 antibody comprises atezolizumab, avelumab, durvalumab, BMS-036559, or CK-301.
[Invention 1069]
1066. The method of the invention, wherein the immune checkpoint inhibitor comprises an anti-PD1 antibody.
[Invention 1070]
1069. The method of the invention 1069, wherein the anti-PD1 antibody comprises nivolumab, pembrolizumab, pidilizumab, AMP-223, AMP-514, cemiplimab, or PDR-001.
[Present invention 1071]
1066. The method of the invention 1066, wherein the immune checkpoint inhibitor comprises an anti-CTLA-4 antibody.
[Invention 1072]
1071. The method of the invention 1071, wherein the anti-CTLA-4 therapy comprises ipilimumab or tremelimumab.
[Invention 1073]
1066. The method of the invention 1066, wherein the second anti-cancer therapy comprises adoptive T cell therapy.
[Present invention 1074]
1074. The method of the invention 1074, wherein adoptive T cell therapy is administered subsequent to administration of the MTAP enzyme.
[Present invention 1075]
A method of treating a patient with a tumor, including the following steps:
Subjecting the patient to adoptive T cell therapy comprising T cells that have been engineered to express the MTAP enzyme.
[Invention 1076]
The method of any of the inventions 1042-1075, wherein metastasis of cancer is delayed, reduced, or prevented.
[Invention 1077]
MTAP enzyme of any of the inventions 1001-1031, nucleic acid of any of the inventions 1032-1036, or pharmaceutical composition of the invention 1041 for the manufacture of a medicament for therapeutic application to patients with tumors. Use of.
Other objects, features and advantages of the invention will become apparent from the detailed description below. It is to be understood, however, that the detailed description and specific examples, while indicating preferred embodiments of the invention, are given by way of example only. From this detailed description, various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art.
Claims (15)
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| LT3472207T (en) | 2016-06-20 | 2021-05-10 | F-Star Delta Limited | Binding molecules binding pd-l1 and lag-3 |
| GB201611530D0 (en) | 2016-07-01 | 2016-08-17 | Alligator Bioscience Ab | Novel polypeptides |
| JOP20190013A1 (en) | 2016-08-25 | 2019-01-31 | Lilly Co Eli | Anti-tim-3 antibodies |
| CN110062885A (en) | 2016-11-01 | 2019-07-26 | 安奈普泰斯生物有限公司 | For the antibody of T cell immunoglobulin and mucin 3 (TIM-3) |
| GB201619648D0 (en) | 2016-11-21 | 2017-01-04 | Alligator Bioscience Ab | Novel antibodies and uses thereof |
| EP3548638A1 (en) * | 2016-12-01 | 2019-10-09 | GlaxoSmithKline Intellectual Property Development Limited | Methods of treating cancer |
| US20200024351A1 (en) | 2017-04-03 | 2020-01-23 | Jounce Therapeutics, Inc. | Compositions and Methods for the Treatment of Cancer |
| US20220135670A1 (en) | 2017-04-27 | 2022-05-05 | Tesaro, Inc. | Antibody agents directed against lymphocyte activation gene-3 (lag-3) and uses thereof |
| JP2020518622A (en) | 2017-05-02 | 2020-06-25 | アリゲーター・バイオサイエンス・アーベー | Bispecific antibodies to OX40 and CTLA-4 |
| JP7016958B2 (en) | 2017-12-21 | 2022-02-07 | ボード オブ リージェンツ，ザ ユニバーシティ オブ テキサス システム | Enzyme-mediated depletion of adenosine and / or methylthioadenosine |
| WO2021141977A1 (en) | 2020-01-07 | 2021-07-15 | Board Of Regents, The University Of Texas System | Improved human methyl thioadenosine/adenosine depleting enzyme variants for cancer therapy |
-
2021
- 2021-01-06 WO PCT/US2021/012291 patent/WO2021141977A1/en unknown
- 2021-01-06 CA CA3161733A patent/CA3161733A1/en active Pending
- 2021-01-06 AU AU2021206202A patent/AU2021206202A1/en active Pending
- 2021-01-06 US US17/427,519 patent/US11396647B2/en active Active
- 2021-01-06 CN CN202180017988.0A patent/CN115244175A/en active Pending
- 2021-01-06 MX MX2022008412A patent/MX2022008412A/en unknown
- 2021-01-06 KR KR1020227024213A patent/KR20220124718A/en unknown
- 2021-01-06 BR BR112022012918A patent/BR112022012918A2/en not_active Application Discontinuation
- 2021-01-06 EP EP21738966.7A patent/EP4087922A4/en active Pending
- 2021-01-06 JP JP2022541785A patent/JP2023509516A/en active Pending
- 2021-01-06 IL IL294557A patent/IL294557A/en unknown
- 2021-11-01 US US17/516,639 patent/US11591579B2/en active Active
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