JPWO2019246110A5 - - Google Patents
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- JPWO2019246110A5 JPWO2019246110A5 JP2021520087A JP2021520087A JPWO2019246110A5 JP WO2019246110 A5 JPWO2019246110 A5 JP WO2019246110A5 JP 2021520087 A JP2021520087 A JP 2021520087A JP 2021520087 A JP2021520087 A JP 2021520087A JP WO2019246110 A5 JPWO2019246110 A5 JP WO2019246110A5
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- 125000003275 alpha amino acid group Chemical group 0.000 claims description 64
- 102000004965 antibodies Human genes 0.000 claims description 54
- 108090001123 antibodies Proteins 0.000 claims description 54
- 239000000427 antigen Substances 0.000 claims description 39
- 102000038129 antigens Human genes 0.000 claims description 39
- 108091007172 antigens Proteins 0.000 claims description 39
- 206010014733 Endometrial cancer Diseases 0.000 claims description 26
- 201000011510 cancer Diseases 0.000 claims description 9
- 206010061424 Anal cancer Diseases 0.000 claims description 6
- 201000011165 anus cancer Diseases 0.000 claims description 6
- 108010047041 Complementarity Determining Regions Proteins 0.000 claims description 4
- 102000010567 DNA Polymerase II Human genes 0.000 claims description 4
- 108010063113 DNA Polymerase II Proteins 0.000 claims description 4
- 101700008821 EXO Proteins 0.000 claims description 4
- 101700083023 EXRN Proteins 0.000 claims description 4
- 230000035693 Fab Effects 0.000 claims description 4
- 208000002030 Merkel Cell Carcinoma Diseases 0.000 claims description 4
- 229920002393 Microsatellite Polymers 0.000 claims description 4
- 206010029266 Neuroendocrine carcinoma of the skin Diseases 0.000 claims description 4
- 230000033607 mismatch repair Effects 0.000 claims description 4
- 230000035772 mutation Effects 0.000 claims description 4
- 206010005003 Bladder cancer Diseases 0.000 claims description 2
- 206010006187 Breast cancer Diseases 0.000 claims description 2
- 206010018338 Glioma Diseases 0.000 claims description 2
- 206010073071 Hepatocellular carcinoma Diseases 0.000 claims description 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 2
- 206010025323 Lymphomas Diseases 0.000 claims description 2
- 206010029260 Neuroblastoma Diseases 0.000 claims description 2
- 208000002154 Non-Small-Cell Lung Carcinoma Diseases 0.000 claims description 2
- 108009000071 Non-small cell lung cancer Proteins 0.000 claims description 2
- 206010025310 Other lymphomas Diseases 0.000 claims description 2
- 206010033128 Ovarian cancer Diseases 0.000 claims description 2
- 208000008443 Pancreatic Carcinoma Diseases 0.000 claims description 2
- 206010035226 Plasma cell myeloma Diseases 0.000 claims description 2
- 206010038038 Rectal cancer Diseases 0.000 claims description 2
- 206010038389 Renal cancer Diseases 0.000 claims description 2
- 206010039491 Sarcoma Diseases 0.000 claims description 2
- 201000009030 carcinoma Diseases 0.000 claims description 2
- 201000011231 colorectal cancer Diseases 0.000 claims description 2
- 230000002950 deficient Effects 0.000 claims description 2
- 231100000844 hepatocellular carcinoma Toxicity 0.000 claims description 2
- 201000010982 kidney cancer Diseases 0.000 claims description 2
- 201000005202 lung cancer Diseases 0.000 claims description 2
- 201000009251 multiple myeloma Diseases 0.000 claims description 2
- 201000002528 pancreatic cancer Diseases 0.000 claims description 2
- 201000001275 rectum cancer Diseases 0.000 claims description 2
- 201000005112 urinary bladder cancer Diseases 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 30
Description
その他の実施形態
本発明の態様を下記項にさらに記載する：
［項１］
子宮内膜癌の治療を必要とするヒト対象における前記子宮内膜癌を治療する方法であって、ヒトＰＤ－１に結合する抗体またはその抗原結合フラグメントの治療有効量を前記ヒト対象に投与することを含み、前記抗体またはその抗原結合フラグメントが、ＶＨ相補性決定領域（ＣＤＲ）１、ＶＨ ＣＤＲ２、及びＶＨ ＣＤＲ３を含む重鎖可変（ＶＨ）ドメインであって、
前記ＶＨ ＣＤＲ１が、アミノ酸配列ＳＹＷＭＮ（配列番号６）を含み、
前記ＶＨ ＣＤＲ２が、アミノ酸配列ＶＩＨＰＳＤＳＥＴＷＬＤＱＫＦＫＤ（配列番号７）を含み、
前記ＶＨ ＣＤＲ３が、アミノ酸配列ＥＨＹＧＴＳＰＦＡＹ（配列番号８）を含む、前記ＶＨドメインを含み、
前記抗体が、ＶＬ ＣＤＲ１、ＶＬ ＣＤＲ２、及びＶＬ ＣＤＲ３を含む軽鎖可変（ＶＬ）ドメインであって、
前記ＶＬ ＣＤＲ１が、アミノ酸配列ＲＡＳＥＳＶＤＮＹＧＭＳＦＭＮＷ（配列番号９）を含み、
前記ＶＬ ＣＤＲ２が、アミノ酸配列ＡＡＳＮＱＧＳ（配列番号１０）を含み、
前記ＶＬ ＣＤＲ３が、アミノ酸配列ＱＱＳＫＥＶＰＹＴ（配列番号１１）を含む、前記ＶＬドメインを含む、前記方法。
［項２］
前記子宮内膜癌が、高頻度マイクロサテライト不安定性子宮内膜癌である、上記項１に記載の方法。
［項３］
前記子宮内膜癌が、ミスマッチ修復機構欠損（ｄＭＭＲ）子宮内膜癌である、上記項１に記載の方法。
［項４］
前記子宮内膜癌が、ＤＮＡポリメラーゼε（ＰＯＬＥ）エキソヌクレアーゼドメイン変異陽性子宮内膜癌である、上記項１に記載の方法。
［項５］
メルケル細胞癌の治療を必要とするヒト対象における前記メルケル細胞癌を治療する方法であって、ヒトＰＤ－１に結合する抗体またはその抗原結合フラグメントの治療有効量を前記ヒト対象に投与することを含み、前記抗体またはその抗原結合フラグメントが、ＶＨ ＣＤＲ１、ＶＨ ＣＤＲ２、及びＶＨ ＣＤＲ３を含むＶＨドメインであって、
前記ＶＨ ＣＤＲ１が、アミノ酸配列ＳＹＷＭＮ（配列番号６）を含み、
前記ＶＨ ＣＤＲ２が、アミノ酸配列ＶＩＨＰＳＤＳＥＴＷＬＤＱＫＦＫＤ（配列番号７）を含み、
前記ＶＨ ＣＤＲ３が、アミノ酸配列ＥＨＹＧＴＳＰＦＡＹ（配列番号８）を含む、前記ＶＨドメインを含み、
前記抗体が、ＶＬ ＣＤＲ１、ＶＬ ＣＤＲ２、及びＶＬ ＣＤＲ３を含むＶＬドメインであって、
前記ＶＬ ＣＤＲ１が、アミノ酸配列ＲＡＳＥＳＶＤＮＹＧＭＳＦＭＮＷ（配列番号９）を含み、
前記ＶＬ ＣＤＲ２が、アミノ酸配列ＡＡＳＮＱＧＳ（配列番号１０）を含み、
前記ＶＬ ＣＤＲ３が、アミノ酸配列ＱＱＳＫＥＶＰＹＴ（配列番号１１）を含む、前記ＶＬドメインを含む、前記方法。
［項６］
肛門癌の治療を必要とするヒト対象における前記肛門癌を治療する方法であって、ヒトＰＤ－１に結合する抗体またはその抗原結合フラグメントの治療有効量を前記ヒト対象に投与することを含み、前記抗体またはその抗原結合フラグメントが、ＶＨ ＣＤＲ１、ＶＨ ＣＤＲ２、及びＶＨ ＣＤＲ３を含むＶＨドメインであって、
前記ＶＨ ＣＤＲ１が、アミノ酸配列ＳＹＷＭＮ（配列番号６）を含み、
前記ＶＨ ＣＤＲ２が、アミノ酸配列ＶＩＨＰＳＤＳＥＴＷＬＤＱＫＦＫＤ（配列番号７）を含み、
前記ＶＨ ＣＤＲ３が、アミノ酸配列ＥＨＹＧＴＳＰＦＡＹ（配列番号８）を含む、前記ＶＨドメインを含み、
前記抗体が、ＶＬ ＣＤＲ１、ＶＬ ＣＤＲ２、及びＶＬ ＣＤＲ３を含むＶＬドメインであって、
前記ＶＬ ＣＤＲ１が、アミノ酸配列ＲＡＳＥＳＶＤＮＹＧＭＳＦＭＮＷ（配列番号９）を含み、
前記ＶＬ ＣＤＲ２が、アミノ酸配列ＡＡＳＮＱＧＳ（配列番号１０）を含み、
前記ＶＬ ＣＤＲ３が、アミノ酸配列ＱＱＳＫＥＶＰＹＴ（配列番号１１）を含む、前記ＶＬドメインを含む、前記方法。
［項７］
前記抗体または抗原結合フラグメントが、１ｍｇ／ｋｇの用量で２週間に１回投与される、上記項１～６のいずれか１項に記載の方法。
［項８］
前記抗体または抗原結合フラグメントが、３ｍｇ／ｋｇの用量で２週間に１回投与される、上記項１～６のいずれか１項に記載の方法。
［項９］
前記抗体または抗原結合フラグメントが、３ｍｇ／ｋｇの用量で４週間に１回投与される、上記項１～６のいずれか１項に記載の方法。
［項１０］
前記抗体または抗原結合フラグメントが、１０ｍｇ／ｋｇの用量で２週間に１回投与される、上記項１～６のいずれか１項に記載の方法。
［項１１］
前記抗体または抗原結合フラグメントが、１０ｍｇ／ｋｇの用量で４週間に１回投与される、上記項１～６のいずれか１項に記載の方法。
［項１２］
がんの治療を必要とするヒト対象における前記がんを治療する方法であって、ヒトＰＤ－１に結合する抗体またはその抗原結合フラグメントの有効固定用量を前記ヒト対象に投与することを含み、前記抗体またはその抗原結合フラグメントが、ＶＨ ＣＤＲ１、ＶＨ ＣＤＲ２、及びＶＨ ＣＤＲ３を含むＶＨドメインであって、
前記ＶＨ ＣＤＲ１が、アミノ酸配列ＳＹＷＭＮ（配列番号６）を含み、
前記ＶＨ ＣＤＲ２が、アミノ酸配列ＶＩＨＰＳＤＳＥＴＷＬＤＱＫＦＫＤ（配列番号７）を含み、
前記ＶＨ ＣＤＲ３が、アミノ酸配列ＥＨＹＧＴＳＰＦＡＹ（配列番号８）を含む、前記ＶＨドメインを含み、
前記抗体が、ＶＬ ＣＤＲ１、ＶＬ ＣＤＲ２、及びＶＬ ＣＤＲ３を含むＶＬドメインであって、
前記ＶＬ ＣＤＲ１が、アミノ酸配列ＲＡＳＥＳＶＤＮＹＧＭＳＦＭＮＷ（配列番号９）を含み、
前記ＶＬ ＣＤＲ２が、アミノ酸配列ＡＡＳＮＱＧＳ（配列番号１０）を含み、
前記ＶＬ ＣＤＲ３が、アミノ酸配列ＱＱＳＫＥＶＰＹＴ（配列番号１１）を含む、前記ＶＬドメインを含む、前記方法。
［項１３］
前記がんが、肛門癌、膀胱癌、乳癌、結腸直腸癌、子宮内膜癌、肝細胞癌、神経膠腫、腎臓癌、肺癌、メルケル細胞癌、多発性骨髄腫、神経芽腫、非ホジキンリンパ腫、非小細胞肺癌、卵巣癌、膵臓癌、直腸癌、または肉腫である、上記項１２に記載の方法。
［項１４］
前記子宮内膜癌が、高頻度マイクロサテライト不安定性（ＭＳＩ－Ｈ）子宮内膜癌、ミスマッチ修復機構欠損（ｄＭＭＲ）子宮内膜癌、及びＤＮＡポリメラーゼε（ＰＯＬＥ）エキソヌクレアーゼドメイン変異陽性子宮内膜癌からなる群より選択される、上記項１３に記載の方法。
［項１５］
前記ＶＨドメインが、配列番号４に記載のアミノ酸配列を含む、上記項１～１４のいずれか１項に記載の方法。
［項１６］
前記抗体が、重鎖を含み、前記重鎖が、配列番号２に記載のアミノ酸配列を含む、上記項１～１４のいずれか１項に記載の方法。
［項１７］
前記ＶＬドメインが、配列番号５に記載のアミノ酸配列を含む、上記項１～１４のいずれか１項に記載の方法。
［項１８］
前記抗体が、軽鎖を含み、前記軽鎖が、配列番号３に記載のアミノ酸配列を含む、上記項１～１４のいずれか１項に記載の方法。
［項１９］
前記ＶＨドメインが、配列番号４に記載のアミノ酸配列を含み、前記ＶＬドメインが、配列番号５に記載のアミノ酸配列を含む、上記項１～１４のいずれか１項に記載の方法。
［項２０］
前記抗体が、重鎖及び軽鎖を含み、前記重鎖が、配列番号２に記載のアミノ酸配列を含み、前記軽鎖が、配列番号３に記載のアミノ酸配列を含む、上記項１～１４のいずれか１項に記載の方法。
［項２１］
前記抗体が、ヒト化抗体である、上記項１～１４のいずれか１項に記載の方法。
［項２２］
前記抗原結合フラグメントが、１本鎖抗体、Ｆａｂフラグメント、Ｆ（ａｂ’）２フラグメント、Ｆａｂ’フラグメント、Ｆｓｃフラグメント、Ｆｖフラグメント、ｓｃＦｖ、ｓｃ（Ｆｖ）２、またはダイアボディである、上記項１～１４のいずれか１項に記載の方法。
［項２３］
前記抗体または抗原結合フラグメントが、静脈内に投与される、上記項１～２２のいずれか１項に記載の方法。
［項２４］
前記抗体または抗原結合フラグメントが、３７５ｍｇの用量で３週間に１回投与される、上記項１～２３のいずれか１項に記載の方法。
［項２５］
前記抗体または抗原結合フラグメントが、５００ｍｇの用量で４週間に１回投与される、上記項１～２３のいずれか１項に記載の方法。
［項２６］
前記抗体または抗原結合フラグメントが、７５０ｍｇの用量で４週間に１回投与される、上記項１～２３のいずれか１項に記載の方法。
本発明をその詳細な説明と併せて説明してきたが、以上の説明は、添付の特許請求の範囲によって定義される本発明の範囲を例示することを意図しており、限定することは意図していない。その他の態様、利点、及び変更は以下の特許請求の範囲内にある。
Other embodiments
The embodiments of the present invention are further described in the following sections:
[Item 1]
A method of treating the endometrial cancer in a human subject requiring treatment of the endometrial cancer, wherein a therapeutically effective amount of an antibody that binds to human PD-1 or an antigen-binding fragment thereof is administered to the human subject. The antibody or antigen binding fragment thereof is a heavy chain variable (VH) domain comprising VH complementarity determining regions (CDRs) 1, VH CDR2, and VH CDR3.
The VH CDR1 comprises the amino acid sequence SYWMN (SEQ ID NO: 6).
The VH CDR2 comprises the amino acid sequence VIHPSDSETWLDQKFKD (SEQ ID NO: 7).
The VH CDR3 comprises the VH domain comprising the amino acid sequence EHYGTSPFAY (SEQ ID NO: 8).
The antibody is a light chain variable (VL) domain comprising VL CDR1, VL CDR2, and VL CDR3.
The VL CDR1 comprises the amino acid sequence RASESVDNYGMSFMNW (SEQ ID NO: 9).
The VL CDR2 comprises the amino acid sequence AASNQGS (SEQ ID NO: 10).
The method, wherein the VL CDR3 comprises the VL domain comprising the amino acid sequence QQSKEVPYT (SEQ ID NO: 11).
[Item 2]
Item 2. The method according to Item 1, wherein the endometrial cancer is a high-frequency microsatellite instability endometrial cancer.
[Item 3]
Item 2. The method according to Item 1, wherein the endometrial cancer is a mismatch repair mechanism deficient (dMMR) endometrial cancer.
[Item 4]
Item 2. The method according to Item 1, wherein the endometrial cancer is a DNA polymerase ε (POLE) exonuclease domain mutation-positive endometrial cancer.
[Item 5]
A method for treating the Merkel cell carcinoma in a human subject requiring treatment for the Merkel cell carcinoma, wherein a therapeutically effective amount of an antibody that binds to human PD-1 or an antigen-binding fragment thereof is administered to the human subject. The antibody or antigen-binding fragment thereof comprises a VH domain comprising VH CDR1, VH CDR2, and VH CDR3.
The VH CDR1 comprises the amino acid sequence SYWMN (SEQ ID NO: 6).
The VH CDR2 comprises the amino acid sequence VIHPSDSETWLDQKFKD (SEQ ID NO: 7).
The VH CDR3 comprises the VH domain comprising the amino acid sequence EHYGTSPFAY (SEQ ID NO: 8).
The antibody is a VL domain comprising VL CDR1, VL CDR2, and VL CDR3.
The VL CDR1 comprises the amino acid sequence RASESVDNYGMSFMNW (SEQ ID NO: 9).
The VL CDR2 comprises the amino acid sequence AASNQGS (SEQ ID NO: 10).
The method, wherein the VL CDR3 comprises the VL domain comprising the amino acid sequence QQSKEVPYT (SEQ ID NO: 11).
[Item 6]
A method of treating the anal cancer in a human subject in need of treatment for the anal cancer, comprising administering to the human subject a therapeutically effective amount of an antibody that binds to human PD-1 or an antigen-binding fragment thereof. The antibody or antigen-binding fragment thereof is a VH domain containing VH CDR1, VH CDR2, and VH CDR3.
The VH CDR1 comprises the amino acid sequence SYWMN (SEQ ID NO: 6).
The VH CDR2 comprises the amino acid sequence VIHPSDSETWLDQKFKD (SEQ ID NO: 7).
The VH CDR3 comprises the VH domain comprising the amino acid sequence EHYGTSPFAY (SEQ ID NO: 8).
The antibody is a VL domain comprising VL CDR1, VL CDR2, and VL CDR3.
The VL CDR1 comprises the amino acid sequence RASESVDNYGMSFMNW (SEQ ID NO: 9).
The VL CDR2 comprises the amino acid sequence AASNQGS (SEQ ID NO: 10).
The method, wherein the VL CDR3 comprises the VL domain comprising the amino acid sequence QQSKEVPYT (SEQ ID NO: 11).
[Item 7]
Item 6. The method according to any one of Items 1 to 6 above, wherein the antibody or antigen-binding fragment is administered at a dose of 1 mg / kg once every two weeks.
[Item 8]
Item 6. The method according to any one of Items 1 to 6 above, wherein the antibody or antigen-binding fragment is administered at a dose of 3 mg / kg once every two weeks.
[Item 9]
Item 6. The method according to any one of Items 1 to 6 above, wherein the antibody or antigen-binding fragment is administered at a dose of 3 mg / kg once every 4 weeks.
[Item 10]
Item 6. The method according to any one of Items 1 to 6 above, wherein the antibody or antigen-binding fragment is administered at a dose of 10 mg / kg once every two weeks.
[Item 11]
Item 6. The method according to any one of Items 1 to 6 above, wherein the antibody or antigen-binding fragment is administered at a dose of 10 mg / kg once every 4 weeks.
[Item 12]
A method of treating the cancer in a human subject in need of treatment, comprising administering to the human subject an effective fixed dose of an antibody that binds to human PD-1 or an antigen-binding fragment thereof. The antibody or antigen-binding fragment thereof is a VH domain containing VH CDR1, VH CDR2, and VH CDR3.
The VH CDR1 comprises the amino acid sequence SYWMN (SEQ ID NO: 6).
The VH CDR2 comprises the amino acid sequence VIHPSDSETWLDQKFKD (SEQ ID NO: 7).
The VH CDR3 comprises the VH domain comprising the amino acid sequence EHYGTSPFAY (SEQ ID NO: 8).
The antibody is a VL domain comprising VL CDR1, VL CDR2, and VL CDR3.
The VL CDR1 comprises the amino acid sequence RASESVDNYGMSFMNW (SEQ ID NO: 9).
The VL CDR2 comprises the amino acid sequence AASNQGS (SEQ ID NO: 10).
The method, wherein the VL CDR3 comprises the VL domain comprising the amino acid sequence QQSKEVPYT (SEQ ID NO: 11).
[Item 13]
The cancers are anal cancer, bladder cancer, breast cancer, colorectal cancer, endometrial cancer, hepatocellular carcinoma, glioma, kidney cancer, lung cancer, Mercell cell carcinoma, multiple myeloma, neuroblastoma, non-hodgkin. Item 12. The method according to Item 12, wherein the method is lymphoma, non-small cell lung cancer, ovarian cancer, pancreatic cancer, rectal cancer, or sarcoma.
[Item 14]
The endometrial cancers include high-frequency microsatellite instability (MSI-H) endometrial cancer, mismatch repair mechanism deficiency (dMMR) endometrial cancer, and DNA polymerase ε (POLE) exonuclease domain mutation-positive endometrial cancer. Item 13. The method according to Item 13, which is selected from the group consisting of cancer.
[Item 15]
The method according to any one of Items 1 to 14, wherein the VH domain comprises the amino acid sequence set forth in SEQ ID NO: 4.
[Item 16]
The method according to any one of Items 1 to 14, wherein the antibody comprises a heavy chain, and the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 2.
[Item 17]
The method according to any one of Items 1 to 14, wherein the VL domain comprises the amino acid sequence set forth in SEQ ID NO: 5.
[Item 18]
The method according to any one of Items 1 to 14, wherein the antibody comprises a light chain, wherein the light chain comprises the amino acid sequence set forth in SEQ ID NO: 3.
[Item 19]
The method according to any one of Items 1 to 14, wherein the VH domain comprises the amino acid sequence set forth in SEQ ID NO: 4, and the VL domain comprises the amino acid sequence set forth in SEQ ID NO: 5.
[Item 20]
Items 1 to 14 above, wherein the antibody comprises a heavy chain and a light chain, the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 2, and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 3. The method according to any one.
[Item 21]
Item 6. The method according to any one of Items 1 to 14, wherein the antibody is a humanized antibody.
[Item 22]
Items 1 to 1 above, wherein the antigen-binding fragment is a single-chain antibody, Fab fragment, F (ab') 2 fragment, Fab'fragment, Fsc fragment, Fv fragment, scFv, sc (Fv) 2, or diabody. The method according to any one of 14.
[Item 23]
Item 6. The method according to any one of Items 1 to 22, wherein the antibody or antigen-binding fragment is administered intravenously.
[Item 24]
Item 6. The method according to any one of Items 1 to 23 above, wherein the antibody or antigen-binding fragment is administered at a dose of 375 mg once every 3 weeks.
[Item 25]
Item 6. The method according to any one of Items 1 to 23 above, wherein the antibody or antigen-binding fragment is administered at a dose of 500 mg once every 4 weeks.
[Item 26]
Item 6. The method according to any one of Items 1 to 23 above, wherein the antibody or antigen-binding fragment is administered at a dose of 750 mg once every 4 weeks.
Although the present invention has been described in conjunction with its detailed description, the above description is intended to illustrate and limit the scope of the invention as defined by the appended claims. Not. Other aspects, advantages, and changes are within the scope of the following claims.
Claims (26)
前記ＶＨ ＣＤＲ１が、アミノ酸配列ＳＹＷＭＮ（配列番号６）を含み、
前記ＶＨ ＣＤＲ２が、アミノ酸配列ＶＩＨＰＳＤＳＥＴＷＬＤＱＫＦＫＤ（配列番号７）を含み、
前記ＶＨ ＣＤＲ３が、アミノ酸配列ＥＨＹＧＴＳＰＦＡＹ（配列番号８）を含む、前記ＶＨドメインを含み、
前記抗体またはその抗原結合フラグメントが、ＶＬ ＣＤＲ１、ＶＬ ＣＤＲ２、及びＶＬ ＣＤＲ３を含む軽鎖可変（ＶＬ）ドメインであって、
前記ＶＬ ＣＤＲ１が、アミノ酸配列ＲＡＳＥＳＶＤＮＹＧＭＳＦＭＮＷ（配列番号９）を含み、
前記ＶＬ ＣＤＲ２が、アミノ酸配列ＡＡＳＮＱＧＳ（配列番号１０）を含み、
前記ＶＬ ＣＤＲ３が、アミノ酸配列ＱＱＳＫＥＶＰＹＴ（配列番号１１）を含む、前記ＶＬドメインを含む、前記医薬組成物。 A pharmaceutical composition for treating the endometrial cancer in a human subject in need of treatment of the endometrial cancer, comprising an antibody that binds to human PD-1 or an antigen-binding fragment thereof , said antibody or The antigen binding fragment is a heavy chain variable (VH) domain comprising VH complementarity determining regions (CDRs) 1, VH CDR2, and VH CDR3.
The VH CDR1 comprises the amino acid sequence SYWMN (SEQ ID NO: 6).
The VH CDR2 comprises the amino acid sequence VIHPSDSETWLDQKFKD (SEQ ID NO: 7).
The VH CDR3 comprises the VH domain comprising the amino acid sequence EHYGTSPFAY (SEQ ID NO: 8).
The antibody or antigen-binding fragment thereof is a light chain variable (VL) domain containing VL CDR1, VL CDR2, and VL CDR3.
The VL CDR1 comprises the amino acid sequence RASESVDNYGMSFMNW (SEQ ID NO: 9).
The VL CDR2 comprises the amino acid sequence AASNQGS (SEQ ID NO: 10).
The pharmaceutical composition comprising the VL domain, wherein the VL CDR3 comprises the amino acid sequence QQSKEVPYT (SEQ ID NO: 11).
前記ＶＨ ＣＤＲ１が、アミノ酸配列ＳＹＷＭＮ（配列番号６）を含み、
前記ＶＨ ＣＤＲ２が、アミノ酸配列ＶＩＨＰＳＤＳＥＴＷＬＤＱＫＦＫＤ（配列番号７）を含み、
前記ＶＨ ＣＤＲ３が、アミノ酸配列ＥＨＹＧＴＳＰＦＡＹ（配列番号８）を含む、前記ＶＨドメインを含み、
前記抗体またはその抗原結合フラグメントが、ＶＬ ＣＤＲ１、ＶＬ ＣＤＲ２、及びＶＬ ＣＤＲ３を含むＶＬドメインであって、
前記ＶＬ ＣＤＲ１が、アミノ酸配列ＲＡＳＥＳＶＤＮＹＧＭＳＦＭＮＷ（配列番号９）を含み、
前記ＶＬ ＣＤＲ２が、アミノ酸配列ＡＡＳＮＱＧＳ（配列番号１０）を含み、
前記ＶＬ ＣＤＲ３が、アミノ酸配列ＱＱＳＫＥＶＰＹＴ（配列番号１１）を含む、前記ＶＬドメインを含む、前記医薬組成物。 A pharmaceutical composition for treating the Merkel cell carcinoma in a human subject in need of treatment for Merkel cell carcinoma, comprising an antibody that binds to human PD-1 or an antigen-binding fragment thereof , said antibody or an antigen thereof. The binding fragment is a VH domain comprising VH CDR1, VH CDR2, and VH CDR3.
The VH CDR1 comprises the amino acid sequence SYWMN (SEQ ID NO: 6).
The VH CDR2 comprises the amino acid sequence VIHPSDSETWLDQKFKD (SEQ ID NO: 7).
The VH CDR3 comprises the VH domain comprising the amino acid sequence EHYGTSPFAY (SEQ ID NO: 8).
The antibody or antigen-binding fragment thereof is a VL domain containing VL CDR1, VL CDR2, and VL CDR3.
The VL CDR1 comprises the amino acid sequence RASESVDNYGMSFMNW (SEQ ID NO: 9).
The VL CDR2 comprises the amino acid sequence AASNQGS (SEQ ID NO: 10).
The pharmaceutical composition comprising the VL domain, wherein the VL CDR3 comprises the amino acid sequence QQSKEVPYT (SEQ ID NO: 11).
前記ＶＨ ＣＤＲ１が、アミノ酸配列ＳＹＷＭＮ（配列番号６）を含み、
前記ＶＨ ＣＤＲ２が、アミノ酸配列ＶＩＨＰＳＤＳＥＴＷＬＤＱＫＦＫＤ（配列番号７）を含み、
前記ＶＨ ＣＤＲ３が、アミノ酸配列ＥＨＹＧＴＳＰＦＡＹ（配列番号８）を含む、前記ＶＨドメインを含み、
前記抗体またはその抗原結合フラグメントが、ＶＬ ＣＤＲ１、ＶＬ ＣＤＲ２、及びＶＬ ＣＤＲ３を含むＶＬドメインであって、
前記ＶＬ ＣＤＲ１が、アミノ酸配列ＲＡＳＥＳＶＤＮＹＧＭＳＦＭＮＷ（配列番号９）を含み、
前記ＶＬ ＣＤＲ２が、アミノ酸配列ＡＡＳＮＱＧＳ（配列番号１０）を含み、
前記ＶＬ ＣＤＲ３が、アミノ酸配列ＱＱＳＫＥＶＰＹＴ（配列番号１１）を含む、前記ＶＬドメインを含む、前記医薬組成物。 A pharmaceutical composition for treating the anal cancer in a human subject in need of treatment for the anal cancer, comprising an antibody that binds to human PD-1 or an antigen-binding fragment thereof , and the antibody or an antigen-binding fragment thereof. Is a VH domain comprising VH CDR1, VH CDR2, and VH CDR3.
The VH CDR1 comprises the amino acid sequence SYWMN (SEQ ID NO: 6).
The VH CDR2 comprises the amino acid sequence VIHPSDSETWLDQKFKD (SEQ ID NO: 7).
The VH CDR3 comprises the VH domain comprising the amino acid sequence EHYGTSPFAY (SEQ ID NO: 8).
The antibody or antigen-binding fragment thereof is a VL domain containing VL CDR1, VL CDR2, and VL CDR3.
The VL CDR1 comprises the amino acid sequence RASESVDNYGMSFMNW (SEQ ID NO: 9).
The VL CDR2 comprises the amino acid sequence AASNQGS (SEQ ID NO: 10).
The pharmaceutical composition comprising the VL domain, wherein the VL CDR3 comprises the amino acid sequence QQSKEVPYT (SEQ ID NO: 11).
前記ＶＨ ＣＤＲ１が、アミノ酸配列ＳＹＷＭＮ（配列番号６）を含み、
前記ＶＨ ＣＤＲ２が、アミノ酸配列ＶＩＨＰＳＤＳＥＴＷＬＤＱＫＦＫＤ（配列番号７）を含み、
前記ＶＨ ＣＤＲ３が、アミノ酸配列ＥＨＹＧＴＳＰＦＡＹ（配列番号８）を含む、前記ＶＨドメインを含み、
前記抗体またはその抗原結合フラグメントが、ＶＬ ＣＤＲ１、ＶＬ ＣＤＲ２、及びＶＬ ＣＤＲ３を含むＶＬドメインであって、
前記ＶＬ ＣＤＲ１が、アミノ酸配列ＲＡＳＥＳＶＤＮＹＧＭＳＦＭＮＷ（配列番号９）を含み、
前記ＶＬ ＣＤＲ２が、アミノ酸配列ＡＡＳＮＱＧＳ（配列番号１０）を含み、
前記ＶＬ ＣＤＲ３が、アミノ酸配列ＱＱＳＫＥＶＰＹＴ（配列番号１１）を含む、前記ＶＬドメインを含む、前記医薬組成物。 A pharmaceutical composition for treating the cancer in a human subject in need of treatment of the cancer, which comprises an antibody that binds to human PD-1 or an antigen-binding fragment thereof, and is administered at an effective fixed dose. An antibody or antigen-binding fragment thereof is a VH domain comprising VH CDR1, VH CDR2, and VH CDR3.
The VH CDR1 comprises the amino acid sequence SYWMN (SEQ ID NO: 6).
The VH CDR2 comprises the amino acid sequence VIHPSDSETWLDQKFKD (SEQ ID NO: 7).
The VH CDR3 comprises the VH domain comprising the amino acid sequence EHYGTSPFAY (SEQ ID NO: 8).
The antibody or antigen-binding fragment thereof is a VL domain containing VL CDR1, VL CDR2, and VL CDR3.
The VL CDR1 comprises the amino acid sequence RASESVDNYGMSFMNW (SEQ ID NO: 9).
The VL CDR2 comprises the amino acid sequence AASNQGS (SEQ ID NO: 10).
The pharmaceutical composition comprising the VL domain, wherein the VL CDR3 comprises the amino acid sequence QQSKEVPYT (SEQ ID NO: 11).
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| US62/756,319 | 2018-11-06 | ||
| PCT/US2019/037750 WO2019246110A1 (en) | 2018-06-20 | 2019-06-18 | Anti-pd-1 antibodies and uses thereof |
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