JPWO2021178779A5 - - Google Patents
Download PDFInfo
- Publication number
- JPWO2021178779A5 JPWO2021178779A5 JP2022553139A JP2022553139A JPWO2021178779A5 JP WO2021178779 A5 JPWO2021178779 A5 JP WO2021178779A5 JP 2022553139 A JP2022553139 A JP 2022553139A JP 2022553139 A JP2022553139 A JP 2022553139A JP WO2021178779 A5 JPWO2021178779 A5 JP WO2021178779A5
- Authority
- JP
- Japan
- Prior art keywords
- cancer
- seq
- amino acid
- acid sequence
- antibody
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 34
- 239000000427 antigen Substances 0.000 claims description 12
- 102000036639 antigens Human genes 0.000 claims description 12
- 108091007433 antigens Proteins 0.000 claims description 12
- 239000012634 fragment Substances 0.000 claims description 12
- 229940125904 compound 1 Drugs 0.000 claims description 8
- 206010028980 Neoplasm Diseases 0.000 claims description 6
- 201000011510 cancer Diseases 0.000 claims description 6
- 206010025323 Lymphomas Diseases 0.000 claims description 4
- 201000010536 head and neck cancer Diseases 0.000 claims description 4
- 208000014829 head and neck neoplasm Diseases 0.000 claims description 4
- 201000001441 melanoma Diseases 0.000 claims description 4
- 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 2
- 208000031261 Acute myeloid leukaemia Diseases 0.000 claims description 2
- 208000009746 Adult T-Cell Leukemia-Lymphoma Diseases 0.000 claims description 2
- 208000016683 Adult T-cell leukemia/lymphoma Diseases 0.000 claims description 2
- 206010061424 Anal cancer Diseases 0.000 claims description 2
- 208000007860 Anus Neoplasms Diseases 0.000 claims description 2
- 208000003950 B-cell lymphoma Diseases 0.000 claims description 2
- 206010005003 Bladder cancer Diseases 0.000 claims description 2
- 206010006187 Breast cancer Diseases 0.000 claims description 2
- 208000026310 Breast neoplasm Diseases 0.000 claims description 2
- 208000011691 Burkitt lymphomas Diseases 0.000 claims description 2
- 206010008342 Cervix carcinoma Diseases 0.000 claims description 2
- 206010009944 Colon cancer Diseases 0.000 claims description 2
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 2
- 206010014733 Endometrial cancer Diseases 0.000 claims description 2
- 206010014759 Endometrial neoplasm Diseases 0.000 claims description 2
- 208000000461 Esophageal Neoplasms Diseases 0.000 claims description 2
- 208000022072 Gallbladder Neoplasms Diseases 0.000 claims description 2
- 208000017604 Hodgkin disease Diseases 0.000 claims description 2
- 208000021519 Hodgkin lymphoma Diseases 0.000 claims description 2
- 208000010747 Hodgkins lymphoma Diseases 0.000 claims description 2
- 101000611936 Homo sapiens Programmed cell death protein 1 Proteins 0.000 claims description 2
- 208000008839 Kidney Neoplasms Diseases 0.000 claims description 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 2
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 claims description 2
- 206010052178 Lymphocytic lymphoma Diseases 0.000 claims description 2
- 208000002030 Merkel cell carcinoma Diseases 0.000 claims description 2
- 208000034578 Multiple myelomas Diseases 0.000 claims description 2
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 claims description 2
- 206010029266 Neuroendocrine carcinoma of the skin Diseases 0.000 claims description 2
- 206010030155 Oesophageal carcinoma Diseases 0.000 claims description 2
- 206010033128 Ovarian cancer Diseases 0.000 claims description 2
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 2
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 2
- 206010035226 Plasma cell myeloma Diseases 0.000 claims description 2
- 206010060862 Prostate cancer Diseases 0.000 claims description 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 2
- 206010038389 Renal cancer Diseases 0.000 claims description 2
- 206010039491 Sarcoma Diseases 0.000 claims description 2
- 208000000453 Skin Neoplasms Diseases 0.000 claims description 2
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 2
- 208000024770 Thyroid neoplasm Diseases 0.000 claims description 2
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 2
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims description 2
- 208000033559 Waldenström macroglobulinemia Diseases 0.000 claims description 2
- 201000006966 adult T-cell leukemia Diseases 0.000 claims description 2
- 201000011165 anus cancer Diseases 0.000 claims description 2
- 210000004027 cell Anatomy 0.000 claims description 2
- 201000010881 cervical cancer Diseases 0.000 claims description 2
- 230000001684 chronic effect Effects 0.000 claims description 2
- 208000017763 cutaneous neuroendocrine carcinoma Diseases 0.000 claims description 2
- 201000004101 esophageal cancer Diseases 0.000 claims description 2
- 201000010175 gallbladder cancer Diseases 0.000 claims description 2
- 206010017758 gastric cancer Diseases 0.000 claims description 2
- 208000005017 glioblastoma Diseases 0.000 claims description 2
- 206010073071 hepatocellular carcinoma Diseases 0.000 claims description 2
- 231100000844 hepatocellular carcinoma Toxicity 0.000 claims description 2
- 102000048362 human PDCD1 Human genes 0.000 claims description 2
- 238000001990 intravenous administration Methods 0.000 claims description 2
- 201000010982 kidney cancer Diseases 0.000 claims description 2
- 208000032839 leukemia Diseases 0.000 claims description 2
- 201000007270 liver cancer Diseases 0.000 claims description 2
- 208000014018 liver neoplasm Diseases 0.000 claims description 2
- 201000005202 lung cancer Diseases 0.000 claims description 2
- 208000020816 lung neoplasm Diseases 0.000 claims description 2
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 2
- 230000035772 mutation Effects 0.000 claims description 2
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims description 2
- 201000002528 pancreatic cancer Diseases 0.000 claims description 2
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 2
- 201000009410 rhabdomyosarcoma Diseases 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims description 2
- 201000000849 skin cancer Diseases 0.000 claims description 2
- 230000000087 stabilizing effect Effects 0.000 claims description 2
- 201000011549 stomach cancer Diseases 0.000 claims description 2
- 201000002510 thyroid cancer Diseases 0.000 claims description 2
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims description 2
- 201000005112 urinary bladder cancer Diseases 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims 6
- 229940079593 drug Drugs 0.000 claims 2
- 238000000034 method Methods 0.000 description 23
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
Description
本明細書で説明されるものに加えて、本発明の様々な修正は、前述の説明から当業者には明らかとなろう。そのような修正は、添付の特許請求の範囲の範囲内にあることが意図される。本出願で引用された全ての特許、特許出願、及び刊行物を含む各参考文献は、その全体が参照により本明細書に組み込まれる。
また、本願は、下記の態様も包含する。
［態様１］
患者のがんを治療する方法であって、前記患者に、
（ｉ）以下の構造を有する化合物１：
（ｉｉ）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であって、前記抗体が、（ｉｉ－１）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、及び（ｉｉ－２）ＶＬ ＣＤＲ１、ＶＬ ＣＤＲ２及びＶＬ ＣＤＲ３を含む軽鎖可変（ＶＬ）ドメインを含み、
（ａ）前記ＶＨ ＣＤＲ１がアミノ酸配列ＳＹＷＭＮ（配列番号６）を含み、
（ｂ）前記ＶＨ ＣＤＲ２がアミノ酸配列ＶＩＨＰＳＤＳＥＴＷＬＤＱＫＦＫＤ（配列番号７）を含み、
（ｃ）前記ＶＨ ＣＤＲ３がアミノ酸配列ＥＨＹＧＴＳＰＦＡＹ（配列番号８）を含み、
（ｄ）前記ＶＬ ＣＤＲ１がアミノ酸配列ＲＡＳＥＳＶＤＮＹＧＭＳＦＭＮＷ（配列番号９）を含み、
（ｅ）前記ＶＬ ＣＤＲ２がアミノ酸配列ＡＡＳＮＱＧＳ（配列番号１０）を含み、
（ｆ）前記ＶＬ ＣＤＲ３がアミノ酸配列ＱＱＳＫＥＶＰＹＴ（配列番号１１）を含む、前記抗体またはその抗原結合フラグメントと、
を投与することを含む、前記方法。
［態様２］
化合物１及び前記抗体が同時に投与される、態様１に記載の方法。
［態様３］
化合物１及び前記抗体が逐次的に投与される、態様１に記載の方法。
［態様４］
化合物１が経口投与される、態様１に記載の方法。
［態様５］
前記抗体または抗原結合フラグメントが、静脈内投与を介して投与される、態様１～４のいずれか１つに記載の方法。
［態様６］
前記抗体または抗原結合フラグメントが、３７５ｍｇの用量で、３週間ごとに１回投与される、態様１～５のいずれか１つに記載の方法。
［態様７］
前記抗体または抗原結合フラグメントが、５００ｍｇの用量で、４週間ごとに１回投与される、態様１～５のいずれか１つに記載の方法。
［態様８］
前記抗体または抗原結合フラグメントが、７５０ｍｇの用量で、４週間ごとに１回投与される、態様１～５のいずれか１つに記載の方法。
［態様９］
前記ＶＨドメインが、配列番号４に示されるアミノ酸配列を含む、態様１～８のいずれか１つに記載の方法。
［態様１０］
前記ＶＬドメインが、配列番号５に示されるアミノ酸配列を含む、態様１～９のいずれか１つに記載の方法。
［態様１１］
前記ＶＨドメインが配列番号４に示されるアミノ酸配列を含み、前記ＶＬドメインが配列番号５に示されるアミノ酸配列を含む、態様１～８のいずれか１つに記載の方法。
［態様１２］
（ａ）前記抗体がＦｃ領域及びヒンジドメインを含み、
（ｂ）前記Ｆｃ領域及び前記ヒンジドメインはＩｇＧ４タイプであり、
（ｃ）前記ヒンジドメインが安定化をもたらす変異を含む、
態様１～１１のいずれか１つに記載の方法。
［態様１３］
前記抗体が重鎖を含み、前記重鎖が配列番号２に示されるアミノ酸配列を含む、態様１～１２のいずれか１つに記載の方法。
［態様１４］
前記抗体が軽鎖を含み、前記軽鎖が配列番号３に示されるアミノ酸配列を含む、態様１～１３のいずれか１つに記載の方法。
［態様１５］
前記抗体が重鎖及び軽鎖を含み、前記重鎖が配列番号２に示されるアミノ酸配列を含み、前記軽鎖が配列番号３に示されるアミノ酸配列を含む、態様１～１２のいずれか１つに記載の方法。
［態様１６］
前記抗体が、ＩｇＧ１タイプであるＦｃ領域を含む、態様１～１１のいずれか１つに記載の方法。
［態様１７］
前記抗体が重鎖を含み、前記重鎖が配列番号１３に示されるアミノ酸配列を含む、態様１～１２及び態様１６のいずれか１つに記載の方法。
［態様１８］
前記抗体が軽鎖及び重鎖を含み、前記重鎖が配列番号１３に示されるアミノ酸配列を含み、前記軽鎖が配列番号３に示されるアミノ酸配列を含む、態様１～１２及び態様１６のいずれか１つに記載の方法。
［態様１９］
前記抗体がヒト化抗体である、態様１～１８のいずれか１つに記載の方法。
［態様２０］
前記がんが、肝細胞癌、膀胱癌、乳癌、子宮頸癌、結腸直腸癌、子宮内膜癌、肛門癌、メルケル細胞癌、胃癌、頭頸部癌、腎臓癌、肝臓癌、肺癌、卵巣癌、前立腺癌、食道癌、胆嚢癌、膵臓癌、甲状腺癌、皮膚癌、白血病、多発性骨髄腫、慢性リンパ性リンパ腫、成人Ｔ細胞白血病、Ｂ細胞リンパ腫、急性骨髄性白血病、ホジキンリンパ腫または非ホジキンリンパ腫、ワルデンストレームマクログロブリン血症、有毛細胞リンパ腫、バーキットリンパ腫、膠芽腫、黒色腫、及び横紋肉腫から選択される、態様１～１９のいずれか１つに記載の方法。
［態様２１］
前記がんが、肉腫、頭頸部癌、黒色腫、及び非小細胞肺癌から選択される、態様１～１９のいずれか１つに記載の方法。
Various modifications of the invention in addition to those described herein will become apparent to those skilled in the art from the foregoing description. Such modifications are intended to be within the scope of the appended claims. Each reference, including all patents, patent applications, and publications cited in this application is incorporated by reference in its entirety.
The present application also includes the following aspects.
[Aspect 1]
A method of treating cancer in a patient, the method comprising:
(i) Compound 1 having the following structure:
(ii) an antibody or antigen-binding fragment thereof that binds to human PD-1, the antibody comprising: (ii-1) a heavy chain variable ( (ii-2) a light chain variable (VL) domain comprising VL CDR1, VL CDR2 and VL CDR3;
(a) the VH CDR1 comprises the amino acid sequence SYWMN (SEQ ID NO: 6);
(b) the VH CDR2 comprises the amino acid sequence VIHPSDSETWLDQKFKD (SEQ ID NO: 7);
(c) the VH CDR3 comprises the amino acid sequence EHYGTSPFAY (SEQ ID NO: 8);
(d) the VL CDR1 comprises the amino acid sequence RASESVDNYGMSFMNW (SEQ ID NO: 9);
(e) the VL CDR2 comprises the amino acid sequence AASNQGS (SEQ ID NO: 10);
(f) the antibody or antigen-binding fragment thereof, wherein the VL CDR3 comprises the amino acid sequence QQSKEVPYT (SEQ ID NO: 11);
The method comprising administering.
[Aspect 2]
2. The method of embodiment 1, wherein Compound 1 and said antibody are administered simultaneously.
[Aspect 3]
2. The method of embodiment 1, wherein Compound 1 and said antibody are administered sequentially.
[Aspect 4]
A method according to aspect 1, wherein Compound 1 is administered orally.
[Aspect 5]
5. The method according to any one of aspects 1 to 4, wherein said antibody or antigen-binding fragment is administered via intravenous administration.
[Aspect 6]
The method according to any one of aspects 1 to 5, wherein said antibody or antigen binding fragment is administered at a dose of 375 mg once every three weeks.
[Aspect 7]
The method according to any one of aspects 1 to 5, wherein said antibody or antigen binding fragment is administered at a dose of 500 mg once every four weeks.
[Aspect 8]
The method according to any one of aspects 1 to 5, wherein said antibody or antigen binding fragment is administered at a dose of 750 mg once every four weeks.
[Aspect 9]
9. The method according to any one of aspects 1 to 8, wherein said VH domain comprises the amino acid sequence shown in SEQ ID NO: 4.
[Aspect 10]
The method according to any one of aspects 1 to 9, wherein the VL domain comprises the amino acid sequence shown in SEQ ID NO: 5.
[Aspect 11]
9. The method according to any one of aspects 1 to 8, wherein the VH domain comprises the amino acid sequence shown in SEQ ID NO: 4 and the VL domain comprises the amino acid sequence shown in SEQ ID NO: 5.
[Aspect 12]
(a) the antibody comprises an Fc region and a hinge domain;
(b) the Fc region and the hinge domain are of IgG4 type;
(c) the hinge domain comprises a stabilizing mutation;
The method according to any one of aspects 1 to 11.
[Aspect 13]
13. The method according to any one of aspects 1 to 12, wherein said antibody comprises a heavy chain, said heavy chain comprising the amino acid sequence set forth in SEQ ID NO:2.
[Aspect 14]
14. The method according to any one of aspects 1 to 13, wherein said antibody comprises a light chain, said light chain comprising the amino acid sequence set forth in SEQ ID NO:3.
[Aspect 15]
Any one of aspects 1 to 12, wherein the antibody comprises a heavy chain and a light chain, the heavy chain comprising the amino acid sequence shown in SEQ ID NO: 2, and the light chain comprising the amino acid sequence shown in SEQ ID NO: 3. The method described in.
[Aspect 16]
The method according to any one of aspects 1 to 11, wherein said antibody comprises an Fc region that is of the IgG1 type.
[Aspect 17]
17. The method according to any one of embodiments 1-12 and embodiment 16, wherein the antibody comprises a heavy chain, and the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 13.
[Aspect 18]
Any of aspects 1 to 12 and aspect 16, wherein the antibody comprises a light chain and a heavy chain, the heavy chain comprising the amino acid sequence shown in SEQ ID NO: 13, and the light chain comprising the amino acid sequence shown in SEQ ID NO: 3. The method described in one of the above.
[Aspect 19]
The method according to any one of aspects 1 to 18, wherein said antibody is a humanized antibody.
[Aspect 20]
The cancer is hepatocellular carcinoma, bladder cancer, breast cancer, cervical cancer, colorectal cancer, endometrial cancer, anal cancer, Merkel cell carcinoma, gastric cancer, head and neck cancer, kidney cancer, liver cancer, lung cancer, ovarian cancer. , prostate cancer, esophageal cancer, gallbladder cancer, pancreatic cancer, thyroid cancer, skin cancer, leukemia, multiple myeloma, chronic lymphocytic lymphoma, adult T-cell leukemia, B-cell lymphoma, acute myeloid leukemia, Hodgkin lymphoma or non-Hodgkin 20. The method according to any one of aspects 1 to 19, selected from lymphoma, Waldenström's macroglobulinemia, hairy cell lymphoma, Burkitt's lymphoma, glioblastoma, melanoma, and rhabdomyosarcoma.
[Aspect 21]
The method according to any one of aspects 1 to 19, wherein the cancer is selected from sarcoma, head and neck cancer, melanoma, and non-small cell lung cancer.
Claims (21)
（ｉ）以下の構造：
（ｉｉ）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であって、前記抗体が、（ｉｉ－１）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、及び（ｉｉ－２）ＶＬ ＣＤＲ１、ＶＬ ＣＤＲ２及びＶＬ ＣＤＲ３を含む軽鎖可変（ＶＬ）ドメインを含み、
（ａ）前記ＶＨ ＣＤＲ１がアミノ酸配列ＳＹＷＭＮ（配列番号６）を含み、
（ｂ）前記ＶＨ ＣＤＲ２がアミノ酸配列ＶＩＨＰＳＤＳＥＴＷＬＤＱＫＦＫＤ（配列番号７）を含み、
（ｃ）前記ＶＨ ＣＤＲ３がアミノ酸配列ＥＨＹＧＴＳＰＦＡＹ（配列番号８）を含み、
（ｄ）前記ＶＬ ＣＤＲ１がアミノ酸配列ＲＡＳＥＳＶＤＮＹＧＭＳＦＭＮＷ（配列番号９）を含み、
（ｅ）前記ＶＬ ＣＤＲ２がアミノ酸配列ＡＡＳＮＱＧＳ（配列番号１０）を含み、
（ｆ）前記ＶＬ ＣＤＲ３がアミノ酸配列ＱＱＳＫＥＶＰＹＴ（配列番号１１）を含む、
前記抗体またはその抗原結合フラグメントと、
を含む、前記組合せ医薬。 A combination medicine for treating cancer in a patient, the combination comprising :
( i) Structure of:
(ii) an antibody or antigen-binding fragment thereof that binds to human PD-1, the antibody comprising: (ii-1) a heavy chain variable ( (ii-2) a light chain variable (VL) domain comprising VL CDR1, VL CDR2 and VL CDR3;
(a) the VH CDR1 comprises the amino acid sequence SYWMN (SEQ ID NO: 6);
(b) the VH CDR2 comprises the amino acid sequence VIHPSDSETWLDQKFKD (SEQ ID NO: 7);
(c) the VH CDR3 comprises the amino acid sequence EHYGTSPFAY (SEQ ID NO: 8);
(d) the VL CDR1 comprises the amino acid sequence RASESVDNYGMSFMNW (SEQ ID NO: 9);
(e) the VL CDR2 comprises the amino acid sequence AASNQGS (SEQ ID NO: 10);
(f) said VL CDR3 comprises the amino acid sequence QQSKEVPYT (SEQ ID NO: 11);
the antibody or antigen-binding fragment thereof;
The said combination medicine comprising .
（ｂ）前記Ｆｃ領域及び前記ヒンジドメインはＩｇＧ４タイプであり、
（ｃ）前記ヒンジドメインが安定化をもたらす変異を含む、
請求項１～１１のいずれか１項に記載の組合せ医薬。 (a) the antibody comprises an Fc region and a hinge domain;
(b) the Fc region and the hinge domain are of IgG4 type;
(c) the hinge domain comprises a stabilizing mutation;
The pharmaceutical combination according to any one of claims 1 to 11.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US202062986482P | 2020-03-06 | 2020-03-06 | |
| US62/986,482 | 2020-03-06 | ||
| PCT/US2021/021053 WO2021178779A1 (en) | 2020-03-06 | 2021-03-05 | Combination therapy comprising axl/mer and pd-1/pd-l1 inhibitors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2023516441A JP2023516441A (en) | 2023-04-19 |
| JPWO2021178779A5 true JPWO2021178779A5 (en) | 2024-03-13 |
Family
ID=75223508
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2022553139A Pending JP2023516441A (en) | 2020-03-06 | 2021-03-05 | Combination therapy comprising an AXL/MER inhibitor and a PD-1/PD-L1 inhibitor |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US20210275666A1 (en) |
| EP (1) | EP4114401A1 (en) |
| JP (1) | JP2023516441A (en) |
| KR (1) | KR20230017165A (en) |
| CN (1) | CN115697343A (en) |
| AU (1) | AU2021230385A1 (en) |
| CA (1) | CA3174539A1 (en) |
| CL (1) | CL2022002410A1 (en) |
| IL (1) | IL296065A (en) |
| MX (1) | MX2022010860A (en) |
| TW (1) | TW202140027A (en) |
| WO (1) | WO2021178779A1 (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CR20180516A (en) | 2016-03-28 | 2019-03-05 | Incyte Corp | IPRROLOTRIAZINE COMPOUNDS AS TAM INHIBITORS |
| US11241438B2 (en) | 2018-06-29 | 2022-02-08 | Incyte Corporation | Formulations of an AXL/MER inhibitor |
| IL289525B2 (en) * | 2021-12-30 | 2023-03-01 | B G Negev Technologies And Applications Ltd At Ben Gurion Univ | Antibody conjugates for the treatment of cancer |
Family Cites Families (76)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5179017A (en) | 1980-02-25 | 1993-01-12 | The Trustees Of Columbia University In The City Of New York | Processes for inserting DNA into eucaryotic cells and for producing proteinaceous materials |
| US4399216A (en) | 1980-02-25 | 1983-08-16 | The Trustees Of Columbia University | Processes for inserting DNA into eucaryotic cells and for producing proteinaceous materials |
| US4634665A (en) | 1980-02-25 | 1987-01-06 | The Trustees Of Columbia University In The City Of New York | Processes for inserting DNA into eucaryotic cells and for producing proteinaceous materials |
| US5156840A (en) | 1982-03-09 | 1992-10-20 | Cytogen Corporation | Amine-containing porphyrin derivatives |
| US5057313A (en) | 1986-02-25 | 1991-10-15 | The Center For Molecular Medicine And Immunology | Diagnostic and therapeutic antibody conjugates |
| WO1988007089A1 (en) | 1987-03-18 | 1988-09-22 | Medical Research Council | Altered antibodies |
| IL162181A (en) | 1988-12-28 | 2006-04-10 | Pdl Biopharma Inc | A method of producing humanized immunoglubulin, and polynucleotides encoding the same |
| US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
| DE3920358A1 (en) | 1989-06-22 | 1991-01-17 | Behringwerke Ag | BISPECIFIC AND OLIGO-SPECIFIC, MONO- AND OLIGOVALENT ANTI-BODY CONSTRUCTS, THEIR PRODUCTION AND USE |
| US5859205A (en) | 1989-12-21 | 1999-01-12 | Celltech Limited | Humanised antibodies |
| ATE255131T1 (en) | 1991-06-14 | 2003-12-15 | Genentech Inc | HUMANIZED HEREGULIN ANTIBODIES |
| EP1136556B1 (en) | 1991-11-25 | 2005-06-08 | Enzon, Inc. | Method of producing multivalent antigen-binding proteins |
| US5714350A (en) | 1992-03-09 | 1998-02-03 | Protein Design Labs, Inc. | Increasing antibody affinity by altering glycosylation in the immunoglobulin variable region |
| US5521184A (en) | 1992-04-03 | 1996-05-28 | Ciba-Geigy Corporation | Pyrimidine derivatives and processes for the preparation thereof |
| US5827690A (en) | 1993-12-20 | 1998-10-27 | Genzyme Transgenics Corporatiion | Transgenic production of antibodies in milk |
| US5731168A (en) | 1995-03-01 | 1998-03-24 | Genentech, Inc. | Method for making heteromultimeric polypeptides |
| US5869046A (en) | 1995-04-14 | 1999-02-09 | Genentech, Inc. | Altered polypeptides with increased half-life |
| PT859841E (en) | 1995-08-18 | 2002-11-29 | Morphosys Ag | PROTEIN LIBRARIES / (POLY) PEPTIDES |
| JP4516690B2 (en) | 1998-08-11 | 2010-08-04 | ノバルティス アーゲー | Isoquinoline derivatives having angiogenesis inhibitory activity |
| US6133031A (en) | 1999-08-19 | 2000-10-17 | Isis Pharmaceuticals Inc. | Antisense inhibition of focal adhesion kinase expression |
| GB9905075D0 (en) | 1999-03-06 | 1999-04-28 | Zeneca Ltd | Chemical compounds |
| GB0004890D0 (en) | 2000-03-01 | 2000-04-19 | Astrazeneca Uk Ltd | Chemical compounds |
| BR0212760A (en) | 2001-09-19 | 2004-12-07 | Aventis Pharma Sa | Chemical compounds |
| ATE335490T1 (en) | 2001-10-30 | 2006-09-15 | Novartis Pharma Gmbh | STAUROSPORINE DERIVATIVES AS INHIBITORS OF FLT3 RECEPTOR TYROSINE KINASE ACTION |
| CA2466279A1 (en) | 2001-11-13 | 2003-05-22 | Dana-Farber Cancer Institute, Inc. | Agents that modulate immune cell activation and methods of use thereof |
| PL220952B1 (en) | 2002-01-22 | 2016-01-29 | Warner Lambert Co | 2-(Pyridin-2-ylamino) pyrido [2,3-d] pyrimidin -7-ones |
| PE20040522A1 (en) | 2002-05-29 | 2004-09-28 | Novartis Ag | DIARYLUREA DERIVATIVES DEPENDENT ON PROTEIN KINASE |
| GB0215676D0 (en) | 2002-07-05 | 2002-08-14 | Novartis Ag | Organic compounds |
| TWI335913B (en) | 2002-11-15 | 2011-01-11 | Vertex Pharma | Diaminotriazoles useful as inhibitors of protein kinases |
| UA80767C2 (en) | 2002-12-20 | 2007-10-25 | Pfizer Prod Inc | Pyrimidine derivatives for the treatment of abnormal cell growth |
| ATE514713T1 (en) | 2002-12-23 | 2011-07-15 | Wyeth Llc | ANTIBODIES TO PD-1 AND THEIR USE |
| JP2006524039A (en) | 2003-01-09 | 2006-10-26 | マクロジェニクス，インコーポレーテッド | Identification and production of antibody containing mutant Fc region and use thereof |
| WO2004065416A2 (en) | 2003-01-16 | 2004-08-05 | Genentech, Inc. | Synthetic antibody phage libraries |
| US20050008625A1 (en) | 2003-02-13 | 2005-01-13 | Kalobios, Inc. | Antibody affinity engineering by serial epitope-guided complementarity replacement |
| GB0305929D0 (en) | 2003-03-14 | 2003-04-23 | Novartis Ag | Organic compounds |
| JP4667383B2 (en) | 2003-06-13 | 2011-04-13 | バイオジェン・アイデック・エムエイ・インコーポレイテッド | Aglycosyl anti-CD154 (CD40 ligand) antibody and use thereof |
| NZ545776A (en) | 2003-08-22 | 2009-05-31 | Biogen Idec Inc | Improved antibodies having altered effector function and methods for making the same |
| AR045944A1 (en) | 2003-09-24 | 2005-11-16 | Novartis Ag | ISOQUINOLINE DERIVATIVES 1.4-DISPOSED |
| BRPI0517887A (en) | 2004-11-24 | 2008-10-21 | Novartis Ag | combinations of inhibitors of jaks |
| EP2161336B2 (en) | 2005-05-09 | 2017-03-29 | ONO Pharmaceutical Co., Ltd. | Human monoclonal antibodies to programmed death 1(PD-1) and methods for treating cancer using anti-PD-1 antibodies alone or in combination with other immunotherapeutics |
| AU2006265108C1 (en) | 2005-07-01 | 2013-01-17 | E. R. Squibb & Sons, L.L.C. | Human monoclonal antibodies to programmed death ligand 1 (PD-L1) |
| CN102131828B (en) | 2007-06-18 | 2015-06-17 | 默沙东有限责任公司 | Antibodies to human programmed death receptor pd-1 |
| EP2231656A1 (en) | 2007-12-19 | 2010-09-29 | Amgen Inc. | Fused pyridine, pyrimidine and triazine compounds as cell cycle inhibitors |
| EP2262837A4 (en) | 2008-03-12 | 2011-04-06 | Merck Sharp & Dohme | Pd-1 binding proteins |
| WO2010036959A2 (en) | 2008-09-26 | 2010-04-01 | Dana-Farber Cancer Institute | Human anti-pd-1, pd-l1, and pd-l2 antibodies and uses therefor |
| KR20210060670A (en) | 2008-12-09 | 2021-05-26 | 제넨테크, 인크. | Anti-pd-l1 antibodies and their use to enhance t-cell function |
| PA8852901A1 (en) | 2008-12-22 | 2010-07-27 | Lilly Co Eli | PROTEIN CINASE INHIBITORS |
| US8741295B2 (en) | 2009-02-09 | 2014-06-03 | Universite De La Mediterranee | PD-1 antibodies and PD-L1 antibodies and uses thereof |
| US20130017199A1 (en) | 2009-11-24 | 2013-01-17 | AMPLIMMUNE ,Inc. a corporation | Simultaneous inhibition of pd-l1/pd-l2 |
| WO2011082400A2 (en) | 2010-01-04 | 2011-07-07 | President And Fellows Of Harvard College | Modulators of immunoinhibitory receptor pd-1, and methods of use thereof |
| UY33227A (en) | 2010-02-19 | 2011-09-30 | Novartis Ag | PIRROLOPIRIMIDINE COMPOUNDS AS INHIBITORS OF THE CDK4 / 6 |
| US9163087B2 (en) | 2010-06-18 | 2015-10-20 | The Brigham And Women's Hospital, Inc. | Bi-specific antibodies against TIM-3 and PD-1 for immunotherapy in chronic immune conditions |
| US8907053B2 (en) | 2010-06-25 | 2014-12-09 | Aurigene Discovery Technologies Limited | Immunosuppression modulating compounds |
| SG10201508715YA (en) | 2010-10-25 | 2015-11-27 | G1 Therapeutics Inc | Cdk inhibitors |
| AU2012230896B9 (en) | 2011-03-23 | 2015-06-18 | Amgen Inc. | Fused tricyclic dual inhibitors of CDK 4/6 and FLT3 |
| CN116333138A (en) | 2015-07-30 | 2023-06-27 | 宏观基因有限公司 | PD-1 binding molecules and methods of use thereof |
| MA52119A (en) | 2015-10-19 | 2018-08-29 | Ncyte Corp | HETEROCYCLIC COMPOUNDS USED AS IMMUNOMODULATORS |
| EP3377488B1 (en) | 2015-11-19 | 2022-08-10 | Incyte Corporation | Heterocyclic compounds as immunomodulators |
| ES2916874T3 (en) | 2015-12-17 | 2022-07-06 | Incyte Corp | N-phenyl-pyridine-2-carboxamide derivatives and their use as modulators of the PD-1/PD-L1 protein/protein interaction |
| MD3394033T2 (en) | 2015-12-22 | 2021-04-30 | Incyte Corp | Heterocyclic compounds as immunomodulators |
| CR20180516A (en) | 2016-03-28 | 2019-03-05 | Incyte Corp | IPRROLOTRIAZINE COMPOUNDS AS TAM INHIBITORS |
| AR108396A1 (en) | 2016-05-06 | 2018-08-15 | Incyte Corp | HETEROCYCLIC COMPOUNDS AS IMMUNOMODULATORS |
| MA45116A (en) | 2016-05-26 | 2021-06-02 | Incyte Corp | HETEROCYCLIC COMPOUNDS AS IMMUNOMODULATORS |
| JP7000357B2 (en) | 2016-06-20 | 2022-01-19 | インサイト・コーポレイション | Heterocyclic compounds as immunomodulators |
| WO2018013789A1 (en) | 2016-07-14 | 2018-01-18 | Incyte Corporation | Heterocyclic compounds as immunomodulators |
| MA46045A (en) | 2016-08-29 | 2021-04-28 | Incyte Corp | HETEROCYCLIC COMPOUNDS USED AS IMMUNOMODULATORS |
| JP7303108B2 (en) | 2016-12-22 | 2023-07-04 | インサイト・コーポレイション | Bicyclic heteroaromatic compounds as immunomodulators |
| WO2018119221A1 (en) | 2016-12-22 | 2018-06-28 | Incyte Corporation | Pyridine derivatives as immunomodulators |
| MD3558990T2 (en) | 2016-12-22 | 2023-02-28 | Incyte Corp | Tetrahydro imidazo[4,5-c]pyridine derivatives as PD-L1 internalization inducers |
| WO2018119236A1 (en) | 2016-12-22 | 2018-06-28 | Incyte Corporation | Triazolo[1,5-a]pyridine derivatives as immunomodulators |
| JP7101678B2 (en) | 2016-12-22 | 2022-07-15 | インサイト・コーポレイション | Heterocyclic compounds as immunomodulators |
| US20180177784A1 (en) | 2016-12-22 | 2018-06-28 | Incyte Corporation | Heterocyclic compounds as immunomodulators |
| MX2020003375A (en) | 2017-09-27 | 2020-08-03 | Incyte Corp | Salts of pyrrolotriazine derivatives useful as tam inhibitors. |
| AU2019245288C1 (en) | 2018-03-30 | 2024-01-18 | Incyte Corporation | Heterocyclic compounds as immunomodulators |
| PE20211918A1 (en) | 2018-05-11 | 2021-09-28 | Incyte Corp | TETRAHYDRO-IMIDAZO [4,5-C] PYRIDIN DERIVATIVES AS PD-L1 IMMUNOMODULATORS |
| US11241438B2 (en) | 2018-06-29 | 2022-02-08 | Incyte Corporation | Formulations of an AXL/MER inhibitor |
-
2021
- 2021-03-05 CA CA3174539A patent/CA3174539A1/en active Pending
- 2021-03-05 IL IL296065A patent/IL296065A/en unknown
- 2021-03-05 EP EP21714578.8A patent/EP4114401A1/en active Pending
- 2021-03-05 WO PCT/US2021/021053 patent/WO2021178779A1/en unknown
- 2021-03-05 US US17/193,631 patent/US20210275666A1/en active Pending
- 2021-03-05 CN CN202180030900.9A patent/CN115697343A/en active Pending
- 2021-03-05 KR KR1020227034644A patent/KR20230017165A/en active Search and Examination
- 2021-03-05 TW TW110107831A patent/TW202140027A/en unknown
- 2021-03-05 JP JP2022553139A patent/JP2023516441A/en active Pending
- 2021-03-05 MX MX2022010860A patent/MX2022010860A/en unknown
- 2021-03-05 AU AU2021230385A patent/AU2021230385A1/en active Pending
-
2022
- 2022-09-05 CL CL2022002410A patent/CL2022002410A1/en unknown
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2020504141A5 (en) | ||
| CN109963592B (en) | Use of PD-1 antibodies in combination with VEGF ligands or VEGF receptor inhibitors for the preparation of a medicament for the treatment of tumors | |
| KR20200020902A (en) | Immune treatment for hepatocellular carcinoma (HCC) | |
| JP2020515577A5 (en) | ||
| EP3258965A2 (en) | Combination therapy for cancer treatment | |
| JP2020527332A5 (en) | ||
| RU2679119C2 (en) | Treatment of neoplastic diseases | |
| JP2024016024A5 (en) | ||
| JP2023037000A5 (en) | ||
| US20190117787A1 (en) | Combinations of cd33 antibody drug conjugates with hypomethylating agents | |
| JPWO2021178779A5 (en) | ||
| US20220387404A1 (en) | Treatment of cancer using a combination comprising multi-tyrosine kinase inhibitor and immune checkpoint inhibitor | |
| WO2021213523A1 (en) | Uses of combination of anti-pd-1 antibody and anti-ctla-4 antibody in preventing or treating cancer | |
| JPWO2019228514A5 (en) | ||
| TW202207976A (en) | Methods and combinations for the treatment of cancer using immune checkpoint inhibitor antibodies | |
| JPWO2021224499A5 (en) | ||
| CN115461079A (en) | Combined medicine for treating kidney cancer | |
| JPWO2021190622A5 (en) | ||
| JPWO2020218951A5 (en) | ||
| CN111093703A (en) | Application of immunotherapy agent, nucleoside antimetabolite and platinum combination in preparation of medicine for treating tumors | |
| CN117815387A (en) | Combination pharmaceutical composition of CDK4/6 inhibitor and anti-PD-L1 antibody | |
| KR20240038769A (en) | How to Treat Acute Myeloid Leukemia Using Anti-ILT3 Antibodies | |
| CN116370641A (en) | Combined medicine for treating digestive system malignant tumor | |
| CN113993544A (en) | Multiple variable dose method for treating EGFR-high expressing cancers | |
| JPWO2021178657A5 (en) |