JPWO2019228514A5 - - Google Patents
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- JPWO2019228514A5 JPWO2019228514A5 JP2021517092A JP2021517092A JPWO2019228514A5 JP WO2019228514 A5 JPWO2019228514 A5 JP WO2019228514A5 JP 2021517092 A JP2021517092 A JP 2021517092A JP 2021517092 A JP2021517092 A JP 2021517092A JP WO2019228514 A5 JPWO2019228514 A5 JP WO2019228514A5
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- Prior art keywords
- amino acid
- seq
- acid sequence
- antibody
- cdr3
- Prior art date
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- 125000003275 alpha amino acid group Chemical group 0.000 claims description 147
- 102000004965 antibodies Human genes 0.000 claims description 68
- 108090001123 antibodies Proteins 0.000 claims description 68
- 239000003795 chemical substances by application Substances 0.000 claims description 30
- 239000000203 mixture Substances 0.000 claims description 30
- 201000010099 disease Diseases 0.000 claims description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims description 12
- 238000006467 substitution reaction Methods 0.000 claims description 12
- 201000011510 cancer Diseases 0.000 claims description 9
- 230000004927 fusion Effects 0.000 claims description 9
- 108010047041 Complementarity Determining Regions Proteins 0.000 claims description 8
- 230000035693 Fab Effects 0.000 claims description 6
- NFGXHKASABOEEW-UHFFFAOYSA-N (+)-methoprene Chemical compound COC(C)(C)CCCC(C)CC=CC(C)=CC(=O)OC(C)C NFGXHKASABOEEW-UHFFFAOYSA-N 0.000 claims description 3
- 208000003950 B-Cell Lymphoma Diseases 0.000 claims description 3
- 206010008342 Cervix carcinoma Diseases 0.000 claims description 3
- 206010017758 Gastric cancer Diseases 0.000 claims description 3
- 206010020243 Hodgkin's disease Diseases 0.000 claims description 3
- 201000006743 Hodgkin's lymphoma Diseases 0.000 claims description 3
- 210000004185 Liver Anatomy 0.000 claims description 3
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 3
- 206010025650 Malignant melanoma Diseases 0.000 claims description 3
- 208000002030 Merkel Cell Carcinoma Diseases 0.000 claims description 3
- 206010028980 Neoplasm Diseases 0.000 claims description 3
- 208000002154 Non-Small-Cell Lung Carcinoma Diseases 0.000 claims description 3
- 108009000071 Non-small cell lung cancer Proteins 0.000 claims description 3
- 208000006265 Renal Cell Carcinoma Diseases 0.000 claims description 3
- 108010070144 Single-Chain Antibodies Proteins 0.000 claims description 3
- 102000005632 Single-Chain Antibodies Human genes 0.000 claims description 3
- 208000000587 Small Cell Lung Carcinoma Diseases 0.000 claims description 3
- 206010041067 Small cell lung cancer Diseases 0.000 claims description 3
- 210000001635 Urinary Tract Anatomy 0.000 claims description 3
- 239000002246 antineoplastic agent Substances 0.000 claims description 3
- 201000010881 cervical cancer Diseases 0.000 claims description 3
- 108091006028 chimera Proteins 0.000 claims description 3
- 201000011231 colorectal cancer Diseases 0.000 claims description 3
- 150000002019 disulfides Chemical class 0.000 claims description 3
- 238000007918 intramuscular administration Methods 0.000 claims description 3
- 238000007912 intraperitoneal administration Methods 0.000 claims description 3
- 238000001990 intravenous administration Methods 0.000 claims description 3
- 201000005202 lung cancer Diseases 0.000 claims description 3
- 201000001441 melanoma Diseases 0.000 claims description 3
- 230000035772 mutation Effects 0.000 claims description 3
- 201000011549 stomach cancer Diseases 0.000 claims description 3
- 238000007920 subcutaneous administration Methods 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 229940079593 drugs Drugs 0.000 claims description 2
- 102100007290 CD274 Human genes 0.000 claims 1
- 101710012053 CD274 Proteins 0.000 claims 1
- 239000012216 imaging agent Substances 0.000 description 1
Description
本明細書に記載の抗ＰＤ－Ｌ１抗体剤およびイメージング剤のいずれか１つを含む組成物、キットおよび製造物品も提供される。
特定の実施形態では、例えば以下の項目が提供される。
（項目１）
個体の疾患または状態を処置するための医薬の調製における抗ＰＤ－Ｌ１抗体剤の有効量の使用であって、
前記抗体剤が、重鎖可変領域（Ｖ
Ｈ
）および軽鎖可変領域（Ｖ
Ｌ
）を含む抗体部分を含み、
ａ）前記Ｖ
Ｈ
が、配列番号４１のアミノ酸配列を含む重鎖相補性決定領域１（ＨＣ－ＣＤＲ１）、配列番号４２のアミノ酸配列を含むＨＣ－ＣＤＲ２、および配列番号４３のアミノ酸配列を含むＨＣ－ＣＤＲ３、または前記ＨＣ－ＣＤＲに最大合計約５つのアミノ酸置換を含むそのバリアントを含み；および
ｂ）前記Ｖ
Ｌ
が、配列番号４４のアミノ酸配列を含む軽鎖相補性決定領域１（ＬＣ－ＣＤＲ１）、配列番号４５のアミノ酸配列を含むＬＣ－ＣＤＲ２、および配列番号４６のアミノ酸配列を含むＬＣ－ＣＤＲ３、または前記ＬＣ－ＣＤＲに最大合計約５つのアミノ酸置換を含むそのバリアントを含む、使用。
（項目２）
ａ）前記Ｖ
Ｈ
が、配列番号４１のアミノ酸配列を含むＨＣ－ＣＤＲ１と、配列番号４２のアミノ酸配列を含むＨＣ－ＣＤＲ２と、配列番号４３のアミノ酸配列を含むＨＣ－ＣＤＲ３とを含み；および
ｂ）前記Ｖ
Ｌ
が、配列番号４４のアミノ酸配列を含むＬＣ－ＣＤＲ１と、配列番号４５のアミノ酸配列を含むＬＣ－ＣＤＲ２と、配列番号４６のアミノ酸配列を含むＬＣ－ＣＤＲ３を含む、
項目１に記載の使用。
（項目３）
ａ）前記Ｖ
Ｈ
が、配列番号１、５、９、１１および１３のいずれか１つのアミノ酸配列に対して少なくとも約８０％の配列同一性を有するアミノ酸配列を含み；および／または
ｂ）前記Ｖ
Ｌ
が、配列番号３、７、１５、１７および１９のいずれか１つのアミノ酸配列に対して少なくとも約８０％の配列同一性を有するアミノ酸配列を含む、
項目１または２に記載の使用。
（項目４）
前記抗体部分が、
（ａ）配列番号９のアミノ酸配列を含むＶ
Ｈ
、および配列番号１５のアミノ酸配列を含むＶ
Ｌ
；
（ｂ）配列番号９のアミノ酸配列を含むＶ
Ｈ
、および配列番号１７のアミノ酸配列を含むＶ
Ｌ
；
（ｃ）配列番号９のアミノ酸配列を含むＶ
Ｈ
、および配列番号１９のアミノ酸配列を含むＶ
Ｌ
；
（ｄ）配列番号１１のアミノ酸配列を含むＶ
Ｈ
、および配列番号１５のアミノ酸配列を含むＶ
Ｌ
；
（ｅ）配列番号１１のアミノ酸配列を含むＶ
Ｈ
、および配列番号１７のアミノ酸配列を含むＶ
Ｌ
；
（ｆ）配列番号１１のアミノ酸配列を含むＶ
Ｈ
、および配列番号１９のアミノ酸配列を含むＶ
Ｌ
；
（ｇ）配列番号１３のアミノ酸配列を含むＶ
Ｈ
、および配列番号１５のアミノ酸配列を含むＶ
Ｌ
；
（ｈ）配列番号１３のアミノ酸配列を含むＶ
Ｈ
、および配列番号１７のアミノ酸配列を含むＶ
Ｌ
；または
（ｉ）配列番号１３のアミノ酸配列を含むＶ
Ｈ
、および配列番号１９のアミノ酸配列を含むＶ
Ｌ
を含む、
項目３に記載の使用。
（項目５）
前記抗体部分が、配列番号２１または２３のアミノ酸配列に対して少なくとも約８０％の配列同一性を有するアミノ酸配列を含む、項目１に記載の使用。
（項目６）
個体の疾患または状態を処置するための医薬の調製における抗ＰＤ－Ｌ１抗体剤の有効量の使用であって、
前記抗体剤が、
ａ）配列番号１、５、９、１１および１３のいずれかで示される配列を有する重鎖可変領域（Ｖ
Ｈ
）内のＣＤＲ１、ＣＤＲ２およびＣＤＲ３のアミノ酸配列をそれぞれ含む、ＨＣ－ＣＤＲ１、ＨＣ－ＣＤＲ２およびＨＣ－ＣＤＲ３と、
ｂ）配列番号３、７、１５、１７および１９のいずれかで示される配列を有する軽鎖可変領域（Ｖ
Ｌ
）内のＣＤＲ１、ＣＤＲ２およびＣＤＲ３のアミノ酸配列をそれぞれ含む、ＬＣ－ＣＤＲ１、ＬＣ－ＣＤＲ２およびＬＣ－ＣＤＲ３と
を含む抗体部分を含む、使用。
（項目７）
前記抗体部分が、キメラのものであるか、またはヒト化されている、項目１から６のいずれか一項に記載の使用。
（項目８）
前記抗体部分が、一本鎖Ｆｖ（ｓｃＦｖ）、Ｆａｂ、Ｆａｂ’、Ｆ（ａｂ’）２、Ｆｖ断片、ジスルフィド安定化Ｆｖ断片（ｄｓＦｖ）、（ｄｓＦｖ）
２
、Ｖ
Ｈ
Ｈ、Ｆｖ－Ｆｃ融合体、ｓｃＦｖ－Ｆｃ融合体、ｓｃＦｖ－Ｆｖ融合体、ダイアボディ、トリボディおよびテトラボディからなる群から選択される、項目１から４、６および７のいずれか一項に記載の使用。
（項目９）
前記抗体部分が、一本鎖抗体である、項目１から４および６から８のいずれか一項に記載の使用。
（項目１０）
前記抗体部分が、ｓｃＦｖである、項目９に記載の使用。
（項目１１）
前記抗体部分が、Ｆｃ断片を含む、項目１から４および６から８のいずれか一項に記載の使用。
（項目１２）
前記抗体部分が、全長抗体である、項目１１に記載の使用。
（項目１３）
前記抗体部分が、ＩｇＧ、ＩｇＭ、ＩｇＡ、ＩｇＤおよびＩｇＥからなる群から選択されるアイソタイプを有する、項目１２に記載の使用。
（項目１４）
前記Ｆｃ断片が、ＩｇＧのＦｃ断片である、項目１１から１３のいずれか一項に記載の使用。
（項目１５）
前記Ｆｃ断片が、ＩｇＧ１またはＩｇＧ４のＦｃ断片である、項目１４に記載の使用。
（項目１６）
前記Ｆｃ断片が、Ｈ３１０ＡおよびＨ４３５Ｑ変異を含み、前記アミノ酸位置が、Ｋａｂａｔ番号付けシステムに基づく、項目１１から１５のいずれか一項に記載の使用。
（項目１７）
前記個体が、ヒトである、項目１から１６のいずれか一項に記載の使用。
（項目１８）
前記疾患または状態が、がんである、項目１から１７のいずれか一項に記載の使用。
（項目１９）
前記がんが、黒色腫、腎細胞癌、結腸直腸がん、尿路上皮癌、ホジキンリンパ腫、小細胞肺がん、非小細胞肺がん、頭頸部腫瘍、胃がん、Ｂ細胞リンパ腫、メルケル細胞癌、肝臓がんおよび子宮頸がんからなる群から選択される、項目１８に記載の使用。
（項目２０）
前記抗体剤が、静脈内、腹腔内、筋肉内、皮下または経口投与に好適である、項目１から１９のいずれか一項に記載の使用。
（項目２１）
前記医薬が、第２の薬剤の有効量と組み合わせて使用される、項目１から２０のいずれか一項に記載の使用。
（項目２２）
前記第２の薬剤が、化学療法剤である、項目２１に記載の使用。
（項目２３）
個体の疾患または状態を処置する方法であって、抗ＰＤ－Ｌ１抗体剤の有効量を前記個体に投与するステップを含み、前記抗ＰＤ－Ｌ１抗体剤が、重鎖可変領域（Ｖ
Ｈ
）および軽鎖可変領域（Ｖ
Ｌ
）を含む抗体部分を含み、
ａ）前記Ｖ
Ｈ
が、配列番号４１のアミノ酸配列を含む重鎖相補性決定領域（ＨＣ－ＣＤＲ）１、配列番号４２のアミノ酸配列を含むＨＣ－ＣＤＲ２、および配列番号４３のアミノ酸配列を含むＨＣ－ＣＤＲ３、または前記ＨＣ－ＣＤＲに最大合計約５つのアミノ酸置換を含むそのバリアントを含み；および
ｂ）前記Ｖ
Ｌ
が、配列番号４４のアミノ酸配列を含む軽鎖相補性決定領域（ＬＣ－ＣＤＲ）１、配列番号４５のアミノ酸配列を含むＬＣ－ＣＤＲ２、および配列番号４６のアミノ酸配列を含むＬＣ－ＣＤＲ３、または前記ＬＣ－ＣＤＲに最大合計約５つのアミノ酸置換を含むそのバリアントを含む、方法。
（項目２４）
前記抗ＰＤ－Ｌ１抗体剤の前記有効量が、前記個体の全体重のｋｇ当たり約０．００５μｇ～約５ｇである、項目２３に記載の方法。
（項目２５）
抗ＰＤ－Ｌ１抗体剤および薬学的に許容される担体を含む医薬組成物であって、前記抗体剤が、重鎖可変領域（Ｖ
Ｈ
）および軽鎖可変領域（Ｖ
Ｌ
）を含む抗体部分を含み、
ａ）前記Ｖ
Ｈ
が、配列番号４１のアミノ酸配列を含むＨＣ－ＣＤＲ１、配列番号４２のアミノ酸配列を含むＨＣ－ＣＤＲ２、および配列番号４３のアミノ酸配列を含むＨＣ－ＣＤＲ３、または前記ＨＣ－ＣＤＲに最大合計約５つのアミノ酸置換を含むそのバリアントを含み；および
ｂ）前記Ｖ
Ｌ
が、配列番号４４のアミノ酸配列を含むＬＣ－ＣＤＲ１、配列番号４５のアミノ酸配列を含むＬＣ－ＣＤＲ２、および配列番号４６のアミノ酸配列を含むＬＣ－ＣＤＲ３、または前記ＬＣ－ＣＤＲに最大合計約５つのアミノ酸置換を含むそのバリアントを含む、医薬組成物。
（項目２６）
凍結乾燥されている、項目２５に記載の医薬組成物。
（項目２７）
溶液である、項目２５に記載の医薬組成物。
（項目２８）
約０．００１μｇ～約１０ｇの抗体部分を含む、項目２５から２７のいずれか一項に記載の医薬組成物。
（項目２９）
個体の疾患または状態を処置するためのキットであって、項目２５から２８のいずれか一項に記載の医薬組成物および指示を含むキット。
Also provided are compositions, kits and manufactured articles containing any one of the anti-PD-L1 antibody agents and imaging agents described herein.
In certain embodiments, for example, the following items are provided.
(Item 1)
The use of an effective amount of an anti-PD-L1 antibody agent in the preparation of a pharmaceutical for treating an individual's disease or condition.
The antibody agent comprises an antibody moiety comprising a heavy chain variable region ( VH ) and a light chain variable region ( VL ).
a) The VH contains the heavy chain complementarity determining regions 1 (HC-CDR1) containing the amino acid sequence of SEQ ID NO: 41, HC-CDR2 containing the amino acid sequence of SEQ ID NO: 42, and HC containing the amino acid sequence of SEQ ID NO: 43. -Contains CDR3, or a variant thereof in which the HC-CDRs contain up to a total of about 5 amino acid substitutions; and
b) The VL contains the light chain complementarity determining regions 1 (LC-CDR1) containing the amino acid sequence of SEQ ID NO: 44, LC-CDR2 containing the amino acid sequence of SEQ ID NO: 45, and LC containing the amino acid sequence of SEQ ID NO: 46. -CDR3, or a variant thereof containing up to a total of about 5 amino acid substitutions in said LC-CDR, used.
(Item 2)
a) The VH comprises HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 41, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 42, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 43;
b) The VL comprises LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 44, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 45, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 46.
Use described in item 1.
(Item 3)
a) The VH comprises an amino acid sequence having at least about 80% sequence identity to any one of the amino acid sequences of SEQ ID NOs: 1, 5, 9, 11 and 13; and / or
b) The VL comprises an amino acid sequence having at least about 80% sequence identity to any one of the amino acid sequences of SEQ ID NOs: 3, 7, 15, 17 and 19.
Use according to item 1 or 2.
(Item 4)
The antibody portion
(A) VH containing the amino acid sequence of SEQ ID NO: 9 and VL containing the amino acid sequence of SEQ ID NO : 15.
(B) VH containing the amino acid sequence of SEQ ID NO: 9 and VL containing the amino acid sequence of SEQ ID NO : 17.
(C) VH containing the amino acid sequence of SEQ ID NO: 9 and VL containing the amino acid sequence of SEQ ID NO : 19.
(D) VH containing the amino acid sequence of SEQ ID NO: 11 and VL containing the amino acid sequence of SEQ ID NO : 15.
(E) VH containing the amino acid sequence of SEQ ID NO: 11 and VL containing the amino acid sequence of SEQ ID NO : 17.
(F) VH containing the amino acid sequence of SEQ ID NO: 11 and VL containing the amino acid sequence of SEQ ID NO : 19.
(G) VH containing the amino acid sequence of SEQ ID NO: 13 and VL containing the amino acid sequence of SEQ ID NO : 15.
(H) V H containing the amino acid sequence of SEQ ID NO: 13, and VL containing the amino acid sequence of SEQ ID NO: 17 ; or
(I) Includes VH comprising the amino acid sequence of SEQ ID NO: 13 and VL comprising the amino acid sequence of SEQ ID NO: 19 .
Use described in item 3.
(Item 5)
The use according to item 1, wherein the antibody moiety comprises an amino acid sequence having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 21 or 23.
(Item 6)
The use of an effective amount of an anti-PD-L1 antibody agent in the preparation of a pharmaceutical for treating an individual's disease or condition.
The antibody agent
a) HC-CDR1, HC-containing the amino acid sequences of CDR1, CDR2 and CDR3 in the heavy chain variable region ( VH ) having the sequence represented by any of SEQ ID NOs: 1, 5, 9, 11 and 13, respectively. With CDR2 and HC-CDR3,
b) LC-CDR1, LC- containing the amino acid sequences of CDR1, CDR2 and CDR3 within the light chain variable region ( VL ) having the sequence set forth in any of SEQ ID NOs: 3, 7, 15, 17 and 19, respectively. With CDR2 and LC-CDR3
Including antibody moieties containing, use.
(Item 7)
The use according to any one of items 1 to 6, wherein the antibody moiety is chimeric or humanized.
(Item 8)
The antibody moiety is a single chain Fv (scFv), Fab, Fab', F (ab') 2, Fv fragment, disulfide stabilized Fv fragment (dsFv), (dsFv) 2 , VH H , Fv-Fc fusion. The use according to any one of items 1 to 4, 6 and 7, selected from the group consisting of body, scFv-Fc fusion, scFv-Fv fusion, diabody, tribody and tetrabody.
(Item 9)
The use according to any one of items 1 to 4 and 6 to 8, wherein the antibody moiety is a single chain antibody.
(Item 10)
The use according to item 9, wherein the antibody moiety is scFv.
(Item 11)
The use according to any one of items 1 to 4 and 6 to 8, wherein the antibody moiety comprises an Fc fragment.
(Item 12)
The use according to item 11, wherein the antibody moiety is a full-length antibody.
(Item 13)
The use according to item 12, wherein the antibody moiety has an isotype selected from the group consisting of IgG, IgM, IgA, IgD and IgE.
(Item 14)
The use according to any one of items 11 to 13, wherein the Fc fragment is an IgG Fc fragment.
(Item 15)
The use according to item 14, wherein the Fc fragment is an IgG1 or IgG4 Fc fragment.
(Item 16)
The use according to any one of items 11 to 15, wherein the Fc fragment comprises the H310A and H435Q mutations and the amino acid position is based on the Kabat numbering system.
(Item 17)
The use according to any one of items 1 to 16, wherein the individual is a human.
(Item 18)
The use according to any one of items 1 to 17, wherein the disease or condition is cancer.
(Item 19)
The cancers include melanoma, renal cell carcinoma, colorectal cancer, urinary tract epithelial cancer, hodgkin lymphoma, small cell lung cancer, non-small cell lung cancer, head and neck tumor, gastric cancer, B-cell lymphoma, merkel cell cancer, and liver. The use according to item 18, selected from the group consisting of lung and cervical cancer.
(Item 20)
The use according to any one of items 1 to 19, wherein the antibody agent is suitable for intravenous, intraperitoneal, intramuscular, subcutaneous or oral administration.
(Item 21)
The use according to any one of items 1 to 20, wherein the drug is used in combination with an effective amount of the second agent.
(Item 22)
21. The use according to item 21, wherein the second agent is a chemotherapeutic agent.
(Item 23)
A method of treating a disease or condition of an individual comprising administering to the individual an effective amount of an anti-PD-L1 antibody agent, wherein the anti-PD-L1 antibody agent comprises a heavy chain variable region ( VH ) and Contains an antibody moiety containing a light chain variable region ( VL ),
a) The VH contains the heavy chain complementarity determining regions (HC-CDR) 1 containing the amino acid sequence of SEQ ID NO: 41, HC-CDR2 containing the amino acid sequence of SEQ ID NO: 42, and HC containing the amino acid sequence of SEQ ID NO: 43. -Contains CDR3, or a variant thereof in which the HC-CDRs contain up to a total of about 5 amino acid substitutions; and
b) The VL contains the light chain complementarity determining regions (LC-CDR) 1 containing the amino acid sequence of SEQ ID NO: 44, LC-CDR2 containing the amino acid sequence of SEQ ID NO: 45, and LC containing the amino acid sequence of SEQ ID NO: 46. -A method comprising CDR3, or a variant thereof, wherein the LC-CDR comprises up to a total of about 5 amino acid substitutions.
(Item 24)
23. The method of item 23, wherein the effective amount of the anti-PD-L1 antibody agent is from about 0.005 μg to about 5 g per kg of the total weight of the individual.
(Item 25)
A pharmaceutical composition comprising an anti-PD-L1 antibody agent and a pharmaceutically acceptable carrier, wherein the antibody agent comprises an antibody moiety comprising a heavy chain variable region ( VH ) and a light chain variable region ( VL ). Including,
a) The VH is assigned to HC-CDR1 containing the amino acid sequence of SEQ ID NO: 41, HC-CDR2 containing the amino acid sequence of SEQ ID NO: 42, and HC-CDR3 containing the amino acid sequence of SEQ ID NO: 43, or the HC-CDR. Includes its variants containing up to a total of about 5 amino acid substitutions; and
b) The VL is the LC-CDR1 containing the amino acid sequence of SEQ ID NO: 44, the LC-CDR2 containing the amino acid sequence of SEQ ID NO: 45, and the LC-CDR3 containing the amino acid sequence of SEQ ID NO: 46, or the LC-CDR. A pharmaceutical composition comprising the variant comprising up to a total of about 5 amino acid substitutions.
(Item 26)
25. The pharmaceutical composition according to item 25, which has been lyophilized.
(Item 27)
25. The pharmaceutical composition according to item 25, which is a solution.
(Item 28)
The pharmaceutical composition according to any one of items 25 to 27, comprising an antibody moiety of about 0.001 μg to about 10 g.
(Item 29)
A kit for treating a disease or condition of an individual, comprising the pharmaceutical composition and instructions according to any one of items 25-28.
Claims (50)
前記抗体剤が、重鎖可変領域（ＶＨ）および軽鎖可変領域（ＶＬ）を含む抗体部分を含み、
ａ）前記ＶＨが、配列番号４１のアミノ酸配列を含む重鎖相補性決定領域１（ＨＣ－ＣＤＲ１）、配列番号４２のアミノ酸配列を含むＨＣ－ＣＤＲ２、および配列番号４３のアミノ酸配列を含むＨＣ－ＣＤＲ３、または前記ＨＣ－ＣＤＲに最大合計約５つのアミノ酸置換を含むそのバリアントを含み；および
ｂ）前記ＶＬが、配列番号４４のアミノ酸配列を含む軽鎖相補性決定領域１（ＬＣ－ＣＤＲ１）、配列番号４５のアミノ酸配列を含むＬＣ－ＣＤＲ２、および配列番号４６のアミノ酸配列を含むＬＣ－ＣＤＲ３、または前記ＬＣ－ＣＤＲに最大合計約５つのアミノ酸置換を含むそのバリアントを含む、使用。 The use of an effective amount of an anti-PD-L1 antibody agent in the preparation of a pharmaceutical for treating an individual's disease or condition.
The antibody agent comprises an antibody moiety comprising a heavy chain variable region ( VH ) and a light chain variable region ( VL ).
a) The VH contains the heavy chain complementarity determining regions 1 (HC-CDR1) containing the amino acid sequence of SEQ ID NO: 41, HC-CDR2 containing the amino acid sequence of SEQ ID NO: 42, and HC containing the amino acid sequence of SEQ ID NO: 43. -CDR3, or a variant thereof containing up to about 5 amino acid substitutions in the HC-CDR; and b) the light chain complementarity determining regions 1 (LC-CDR1) in which the VL comprises the amino acid sequence of SEQ ID NO: 44. ), LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 45, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 46, or variants thereof comprising a total of about 5 amino acid substitutions in said LC-CDR.
ｂ）前記ＶＬが、配列番号４４のアミノ酸配列を含むＬＣ－ＣＤＲ１と、配列番号４５のアミノ酸配列を含むＬＣ－ＣＤＲ２と、配列番号４６のアミノ酸配列を含むＬＣ－ＣＤＲ３を含む、
請求項１に記載の使用。 a) The VH comprises HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 41, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 42, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 43; and b. ) The VL comprises LC-CDR1 containing the amino acid sequence of SEQ ID NO: 44, LC-CDR2 containing the amino acid sequence of SEQ ID NO: 45, and LC-CDR3 containing the amino acid sequence of SEQ ID NO: 46.
Use according to claim 1.
ｂ）前記ＶＬが、配列番号３、７、１５、１７および１９のいずれか１つのアミノ酸配列に対して少なくとも約８０％の配列同一性を有するアミノ酸配列を含む、
請求項１または２に記載の使用。 a) said V H comprises an amino acid sequence having at least about 80% sequence identity to any one of the amino acid sequences of SEQ ID NOs: 1, 5, 9, 11 and 13; and / or b) said V L comprises an amino acid sequence having at least about 80% sequence identity to any one of the amino acid sequences of SEQ ID NOs: 3, 7, 15, 17 and 19.
Use according to claim 1 or 2.
（ａ）配列番号９のアミノ酸配列を含むＶＨ、および配列番号１５のアミノ酸配列を含むＶＬ；
（ｂ）配列番号９のアミノ酸配列を含むＶＨ、および配列番号１７のアミノ酸配列を含むＶＬ；
（ｃ）配列番号９のアミノ酸配列を含むＶＨ、および配列番号１９のアミノ酸配列を含むＶＬ；
（ｄ）配列番号１１のアミノ酸配列を含むＶＨ、および配列番号１５のアミノ酸配列を含むＶＬ；
（ｅ）配列番号１１のアミノ酸配列を含むＶＨ、および配列番号１７のアミノ酸配列を含むＶＬ；
（ｆ）配列番号１１のアミノ酸配列を含むＶＨ、および配列番号１９のアミノ酸配列を含むＶＬ；
（ｇ）配列番号１３のアミノ酸配列を含むＶＨ、および配列番号１５のアミノ酸配列を含むＶＬ；
（ｈ）配列番号１３のアミノ酸配列を含むＶＨ、および配列番号１７のアミノ酸配列を含むＶＬ；または
（ｉ）配列番号１３のアミノ酸配列を含むＶＨ、および配列番号１９のアミノ酸配列を含むＶＬを含む、
請求項３に記載の使用。 The antibody portion
(A) VH containing the amino acid sequence of SEQ ID NO: 9 and VL containing the amino acid sequence of SEQ ID NO: 15.
(B) VH containing the amino acid sequence of SEQ ID NO: 9 and VL containing the amino acid sequence of SEQ ID NO: 17.
(C) VH containing the amino acid sequence of SEQ ID NO: 9 and VL containing the amino acid sequence of SEQ ID NO: 19.
(D) VH containing the amino acid sequence of SEQ ID NO: 11 and VL containing the amino acid sequence of SEQ ID NO: 15.
(E) VH containing the amino acid sequence of SEQ ID NO: 11 and VL containing the amino acid sequence of SEQ ID NO: 17.
(F) VH containing the amino acid sequence of SEQ ID NO: 11 and VL containing the amino acid sequence of SEQ ID NO: 19.
(G) VH containing the amino acid sequence of SEQ ID NO: 13 and VL containing the amino acid sequence of SEQ ID NO: 15.
(H) V H comprising the amino acid sequence of SEQ ID NO: 13 and VL comprising the amino acid sequence of SEQ ID NO: 17; or (i) V H comprising the amino acid sequence of SEQ ID NO: 13 and the amino acid sequence of SEQ ID NO: 19. Including VL ,
Use according to claim 3.
前記抗体剤が、
ａ）配列番号１、５、９、１１および１３のいずれかで示される配列を有する重鎖可変領域（ＶＨ）内のＣＤＲ１、ＣＤＲ２およびＣＤＲ３のアミノ酸配列をそれぞれ含む、ＨＣ－ＣＤＲ１、ＨＣ－ＣＤＲ２およびＨＣ－ＣＤＲ３と、
ｂ）配列番号３、７、１５、１７および１９のいずれかで示される配列を有する軽鎖可変領域（ＶＬ）内のＣＤＲ１、ＣＤＲ２およびＣＤＲ３のアミノ酸配列をそれぞれ含む、ＬＣ－ＣＤＲ１、ＬＣ－ＣＤＲ２およびＬＣ－ＣＤＲ３と
を含む抗体部分を含む、使用。 The use of an effective amount of an anti-PD-L1 antibody agent in the preparation of a pharmaceutical for treating an individual's disease or condition.
The antibody agent
a) HC-CDR1, HC-containing the amino acid sequences of CDR1, CDR2 and CDR3 in the heavy chain variable region ( VH ) having the sequence represented by any of SEQ ID NOs: 1, 5, 9, 11 and 13, respectively. With CDR2 and HC-CDR3,
b) LC-CDR1, LC- containing the amino acid sequences of CDR1, CDR2 and CDR3 within the light chain variable region ( VL ) having the sequence set forth in any of SEQ ID NOs: 3, 7, 15, 17 and 19, respectively. Use, including an antibody moiety containing CDR2 and LC-CDR3.
ａ）前記ＶＨが、配列番号４１のアミノ酸配列を含む重鎖相補性決定領域（ＨＣ－ＣＤＲ）１、配列番号４２のアミノ酸配列を含むＨＣ－ＣＤＲ２、および配列番号４３のアミノ酸配列を含むＨＣ－ＣＤＲ３、または前記ＨＣ－ＣＤＲに最大合計約５つのアミノ酸置換を含むそのバリアントを含み；および
ｂ）前記ＶＬが、配列番号４４のアミノ酸配列を含む軽鎖相補性決定領域（ＬＣ－ＣＤＲ）１、配列番号４５のアミノ酸配列を含むＬＣ－ＣＤＲ２、および配列番号４６のアミノ酸配列を含むＬＣ－ＣＤＲ３、または前記ＬＣ－ＣＤＲに最大合計約５つのアミノ酸置換を含むそのバリアントを含む、組成物。 A composition comprising an anti-PD-L1 antibody agent for treating a disease or condition of an individual , wherein the composition is administered to the individual in an effective amount of the anti-PD-L1 antibody agent. The anti - PD-L1 antibody agent comprises an antibody moiety containing a heavy chain variable region ( VH ) and a light chain variable region ( VL ).
a) The VH contains the heavy chain complementarity determining regions (HC-CDR) 1 containing the amino acid sequence of SEQ ID NO: 41, HC-CDR2 containing the amino acid sequence of SEQ ID NO: 42, and HC containing the amino acid sequence of SEQ ID NO: 43. -CDR3, or a variant thereof containing up to about 5 amino acid substitutions in the HC-CDR; and b) the light chain complementarity determining regions (LC-CDRs) in which the VL comprises the amino acid sequence of SEQ ID NO: 44. 1. A composition comprising LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 45, LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 46, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDR.
ａ）前記ＶＨが、配列番号４１のアミノ酸配列を含むＨＣ－ＣＤＲ１、配列番号４２のアミノ酸配列を含むＨＣ－ＣＤＲ２、および配列番号４３のアミノ酸配列を含むＨＣ－ＣＤＲ３、または前記ＨＣ－ＣＤＲに最大合計約５つのアミノ酸置換を含むそのバリアントを含み；および
ｂ）前記ＶＬが、配列番号４４のアミノ酸配列を含むＬＣ－ＣＤＲ１、配列番号４５のアミノ酸配列を含むＬＣ－ＣＤＲ２、および配列番号４６のアミノ酸配列を含むＬＣ－ＣＤＲ３、または前記ＬＣ－ＣＤＲに最大合計約５つのアミノ酸置換を含むそのバリアントを含む、医薬組成物。 A pharmaceutical composition comprising an anti-PD-L1 antibody agent and a pharmaceutically acceptable carrier, wherein the antibody agent comprises an antibody moiety comprising a heavy chain variable region ( VH ) and a light chain variable region ( VL ). Including,
a) The VH is assigned to HC-CDR1 containing the amino acid sequence of SEQ ID NO: 41, HC-CDR2 containing the amino acid sequence of SEQ ID NO: 42, and HC-CDR3 containing the amino acid sequence of SEQ ID NO: 43, or the HC-CDR. Includes variants thereof containing up to a total of about 5 amino acid substitutions; and b) LC- CDR1 containing the amino acid sequence of SEQ ID NO: 44, LC-CDR2 containing the amino acid sequence of SEQ ID NO: 45, and SEQ ID NO: 46. A pharmaceutical composition comprising LC-CDR3 comprising the amino acid sequence of, or a variant thereof comprising up to a total of about 5 amino acid substitutions in said LC-CDR.
ｂ）前記Ｖ b) The V ＬL が、配列番号４４のアミノ酸配列を含むＬＣ－ＣＤＲ１と、配列番号４５のアミノ酸配列を含むＬＣ－ＣＤＲ２と、配列番号４６のアミノ酸配列を含むＬＣ－ＣＤＲ３を含む、Includes LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 44, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 45, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 46.
請求項２３に記載の組成物。23. The composition according to claim 23.
ｂ）前記Ｖ b) The V ＬL が、配列番号３、７、１５、１７および１９のいずれか１つのアミノ酸配列に対して少なくとも約８０％の配列同一性を有するアミノ酸配列を含む、Includes an amino acid sequence having at least about 80% sequence identity to any one of the amino acid sequences of SEQ ID NOs: 3, 7, 15, 17 and 19.
請求項２３または３０に記載の組成物。The composition according to claim 23 or 30.
（ａ）配列番号９のアミノ酸配列を含むＶ (A) V containing the amino acid sequence of SEQ ID NO: 9. ＨH 、および配列番号１５のアミノ酸配列を含むＶ, And V comprising the amino acid sequence of SEQ ID NO: 15. ＬL ；;
（ｂ）配列番号９のアミノ酸配列を含むＶ (B) V containing the amino acid sequence of SEQ ID NO: 9. ＨH 、および配列番号１７のアミノ酸配列を含むＶ, And V containing the amino acid sequence of SEQ ID NO: 17. ＬL ；;
（ｃ）配列番号９のアミノ酸配列を含むＶ (C) V containing the amino acid sequence of SEQ ID NO: 9. ＨH 、および配列番号１９のアミノ酸配列を含むＶ, And V comprising the amino acid sequence of SEQ ID NO: 19. ＬL ；;
（ｄ）配列番号１１のアミノ酸配列を含むＶ (D) V containing the amino acid sequence of SEQ ID NO: 11. ＨH 、および配列番号１５のアミノ酸配列を含むＶ, And V containing the amino acid sequence of SEQ ID NO: 15. ＬL ；;
（ｅ）配列番号１１のアミノ酸配列を含むＶ (E) V containing the amino acid sequence of SEQ ID NO: 11. ＨH 、および配列番号１７のアミノ酸配列を含むＶ, And V containing the amino acid sequence of SEQ ID NO: 17. ＬL ；;
（ｆ）配列番号１１のアミノ酸配列を含むＶ (F) V containing the amino acid sequence of SEQ ID NO: 11. ＨH 、および配列番号１９のアミノ酸配列を含むＶ, And V comprising the amino acid sequence of SEQ ID NO: 19. ＬL ；;
（ｇ）配列番号１３のアミノ酸配列を含むＶ (G) V containing the amino acid sequence of SEQ ID NO: 13. ＨH 、および配列番号１５のアミノ酸配列を含むＶ, And V comprising the amino acid sequence of SEQ ID NO: 15. ＬL ；;
（ｈ）配列番号１３のアミノ酸配列を含むＶ (H) V containing the amino acid sequence of SEQ ID NO: 13. ＨH 、および配列番号１７のアミノ酸配列を含むＶ, And V containing the amino acid sequence of SEQ ID NO: 17. ＬL ；または;or
（ｉ）配列番号１３のアミノ酸配列を含むＶ (I) V containing the amino acid sequence of SEQ ID NO: 13. ＨH 、および配列番号１９のアミノ酸配列を含むＶ, And V comprising the amino acid sequence of SEQ ID NO: 19. ＬL を含む、including,
請求項３１に記載の組成物。The composition according to claim 31.
前記抗体剤が、 The antibody agent
ａ）配列番号１、５、９、１１および１３のいずれかで示される配列を有する重鎖可変領域（Ｖ a) Heavy chain variable region (V) having the sequence represented by any of SEQ ID NOs: 1, 5, 9, 11 and 13. ＨH ）内のＣＤＲ１、ＣＤＲ２およびＣＤＲ３のアミノ酸配列をそれぞれ含む、ＨＣ－ＣＤＲ１、ＨＣ－ＣＤＲ２およびＨＣ－ＣＤＲ３と、), Which contains the amino acid sequences of CDR1, CDR2 and CDR3, respectively, with HC-CDR1, HC-CDR2 and HC-CDR3.
ｂ）配列番号３、７、１５、１７および１９のいずれかで示される配列を有する軽鎖可変領域（Ｖ b) Light chain variable region (V) having the sequence set forth in any of SEQ ID NOs: 3, 7, 15, 17 and 19. ＬL ）内のＣＤＲ１、ＣＤＲ２およびＣＤＲ３のアミノ酸配列をそれぞれ含む、ＬＣ－ＣＤＲ１、ＬＣ－ＣＤＲ２およびＬＣ－ＣＤＲ３と) Containing the amino acid sequences of CDR1, CDR2 and CDR3, respectively, with LC-CDR1, LC-CDR2 and LC-CDR3.
を含む抗体部分を含む、組成物。A composition comprising an antibody moiety comprising.
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| CN116529260A (en) | 2020-06-02 | 2023-08-01 | 当康生物技术有限责任公司 | anti-CD 93 constructs and uses thereof |
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| CN115073599B (en) * | 2021-03-16 | 2023-04-28 | 北京天广实生物技术股份有限公司 | Antibodies that bind PD-L1 and uses thereof |
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| SG11201602283UA (en) * | 2013-09-27 | 2016-04-28 | Genentech Inc | Anti-pdl1 antibody formulations |
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- 2019-05-31 WO PCT/CN2019/089606 patent/WO2019228514A1/en unknown
- 2019-05-31 JP JP2021517092A patent/JP2021525806A/en active Pending
- 2019-05-31 AU AU2019275737A patent/AU2019275737A1/en active Pending
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