JP2012533631A - ヒト血清アルブミン（ＨＳＡ）の変異体と接合したαｖβ３インテグリンに対して選択的なポリペプチドおよびその医薬上の使用 - Google Patents
ヒト血清アルブミン（ＨＳＡ）の変異体と接合したαｖβ３インテグリンに対して選択的なポリペプチドおよびその医薬上の使用 Download PDFInfo
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- C—CHEMISTRY; METALLURGY
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- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
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Landscapes
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| US22694509P | 2009-07-20 | 2009-07-20 | |
| US61/226,945 | 2009-07-20 | ||
| PCT/US2010/042423 WO2011011315A1 (en) | 2009-07-20 | 2010-07-19 | POLYPEPTIDES SELECTIVE FOR AV β3 INTEGRIN CONJUGATED WITH A VARIANT OF HUMAN SERUM ALBUMIN (HSA) AND PHARMACEUTICAL USES THEREOF |
Publications (2)
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| JP2012533631A true JP2012533631A (ja) | 2012-12-27 |
| JP2012533631A5 JP2012533631A5 (https=) | 2013-09-05 |
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| US (1) | US20110015130A1 (https=) |
| EP (1) | EP2456454A4 (https=) |
| JP (1) | JP2012533631A (https=) |
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| CA (1) | CA2768360A1 (https=) |
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| RU (1) | RU2547592C2 (https=) |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2017060462A (ja) * | 2015-08-07 | 2017-03-30 | アレキソ セラピューティクス インク． | Ｓｉｒｐ−アルファ変異体構築物及びその使用 |
| US11208459B2 (en) | 2015-08-07 | 2021-12-28 | ALX Oncology Inc. | Constructs having a SIRP-alpha domain or variant thereof |
| US11613564B2 (en) | 2019-05-31 | 2023-03-28 | ALX Oncology Inc. | Methods of treating cancer |
| US12098214B2 (en) | 2021-05-13 | 2024-09-24 | ALX Oncology Inc. | Combination therapies for treating cancer |
| US12527838B2 (en) | 2019-11-27 | 2026-01-20 | ALX Oncology Inc. | Combination therapies comprising an agent that blocks the interaction between CD47 and SIRPα for treating gastric or gastroesphageal junction cancel |
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101722961B1 (ko) | 2009-02-11 | 2017-04-04 | 알부메딕스 에이/에스 | 알부민 변이체 및 접합체 |
| EP2493921B1 (en) | 2009-10-30 | 2018-09-26 | Albumedix Ltd | Albumin variants |
| US8357652B2 (en) * | 2009-11-20 | 2013-01-22 | Academia Sinica | Anti-tumor fibrillar human serum albumin methods and compositions |
| NZ600544A (en) * | 2009-12-23 | 2014-06-27 | Univ Nat Cheng Kung | Compositions and methods for the treatment of angiogenesis-related eye diseases |
| KR20130020765A (ko) | 2010-02-16 | 2013-02-28 | 메디뮨 엘엘씨 | Ｈｓａ-관련 조성물 및 사용방법 |
| EP2556087A1 (en) | 2010-04-09 | 2013-02-13 | Novozymes Biopharma DK A/S | Albumin derivatives and variants |
| US9045564B2 (en) | 2011-02-15 | 2015-06-02 | Medimmune, Llc | HSA-related compositions and methods of use |
| CA2830660A1 (en) | 2011-05-05 | 2012-11-08 | Novozymes Biopharma Dk A/S | Albumin variants |
| EP2780364A2 (en) | 2011-11-18 | 2014-09-24 | Eleven Biotherapeutics, Inc. | Proteins with improved half-life and other properties |
| DK2825556T3 (en) | 2012-03-16 | 2018-04-16 | Albumedix As | albumin Variants |
| MX2015005363A (es) | 2012-11-08 | 2015-11-06 | Novozymes Biopharma Dk As | Variantes de albumina. |
| JP6886917B2 (ja) * | 2014-08-22 | 2021-06-16 | 國立成功大學Ｎａｔｉｏｎａｌ Ｃｈｅｎｇ Ｋｕｎｇ Ｕｎｉｖｅｒｓｉｔｙ | ロドストミンバリアント、ロドストミンバリアントをコードするポリヌクレオチド、当該ポリヌクレオチドを含む組換え宿主細胞、及びロドストミンバリアントを含む医薬組成物 |
| WO2017001990A1 (en) * | 2015-06-28 | 2017-01-05 | Allgenesis Biotherapeutics Inc. | Fusion proteins for inhibiting angiogenesis |
| JP7007261B2 (ja) | 2015-08-20 | 2022-01-24 | アルブミディクス リミティド | アルブミン変異体及びコンジュゲート |
| US10336812B2 (en) * | 2016-05-10 | 2019-07-02 | Janssen Biotech, Inc. | GDF15 fusion proteins and uses thereof |
| EA202191105A1 (ru) | 2018-10-22 | 2021-08-03 | Янссен Фармацевтика Нв | Слитые белки, полученные из глюкагоноподобного пептида 1 (glp1) и ростового фактора дифференцировки 15 (gdf15), и их применение |
| US20240148839A1 (en) * | 2021-03-16 | 2024-05-09 | Km Biologics Co., Ltd. | Modified human serum albumin-thioredoxin fusion body |
| WO2026022392A1 (en) * | 2024-07-26 | 2026-01-29 | Ospedale San Raffaele S.R.L. | Peptide and conjugates thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH09512706A (ja) * | 1994-03-28 | 1997-12-22 | サイトメッド， インコーポレイテッド | ＫｉｔリガンドおよびＦＬＴ−３／ＦＬＫ−２リガンドの共有結合二量体 |
| WO2008088548A2 (en) * | 2006-12-26 | 2008-07-24 | National Taiwan University | Disintegrin variants and pharmaceutical uses thereof |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4179337A (en) * | 1973-07-20 | 1979-12-18 | Davis Frank F | Non-immunogenic polypeptides |
| JPS6023084B2 (ja) * | 1979-07-11 | 1985-06-05 | 味の素株式会社 | 代用血液 |
| US4640835A (en) * | 1981-10-30 | 1987-02-03 | Nippon Chemiphar Company, Ltd. | Plasminogen activator derivatives |
| US4496689A (en) * | 1983-12-27 | 1985-01-29 | Miles Laboratories, Inc. | Covalently attached complex of alpha-1-proteinase inhibitor with a water soluble polymer |
| EP0206448B1 (en) * | 1985-06-19 | 1990-11-14 | Ajinomoto Co., Inc. | Hemoglobin combined with a poly(alkylene oxide) |
| US4791192A (en) * | 1986-06-26 | 1988-12-13 | Takeda Chemical Industries, Ltd. | Chemically modified protein with polyethyleneglycol |
| AU5939890A (en) * | 1989-06-07 | 1991-01-07 | Genentech Inc. | Platelet aggregation inhibitors and related molecules |
| WO2003042354A2 (en) * | 2001-09-04 | 2003-05-22 | Aventis Pharmaceuticals Inc. | Abrogen polypeptides, nucleic acids encoding them and methods for using them to inhibit angiogenesis |
| WO2003040384A1 (en) * | 2001-11-05 | 2003-05-15 | Board Of Regents, The University Of Texas System | Recombinant antibodies for the detection and neutralization of anthrax toxin |
| KR101271635B1 (ko) * | 2001-12-21 | 2013-06-12 | 휴먼 게놈 사이언시즈, 인코포레이티드 | 알부민 융합 단백질 |
| JP2005529166A (ja) * | 2002-06-07 | 2005-09-29 | ウィスコンシン アルムニ リサーチ ファウンデーション | ペプチドカップリングのための試薬の化学合成 |
| EP1730187A1 (en) * | 2004-03-18 | 2006-12-13 | The University Court Of The University Of Glasgow | Immunosuppressive cytokine |
| WO2008056961A1 (en) * | 2006-11-10 | 2008-05-15 | Boryung Pharmaceutical Co., Ltd | A novel fusion protein, cell lines expressing the same and preparation method thereof |
| US8183201B2 (en) * | 2006-12-26 | 2012-05-22 | National Cheng Kung University | Methods of treating αvβ3 integrin-associated diseases by administering polypeptides selective for αvβ3 integrin |
| NZ600544A (en) * | 2009-12-23 | 2014-06-27 | Univ Nat Cheng Kung | Compositions and methods for the treatment of angiogenesis-related eye diseases |
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- 2010-07-19 AR ARP100102628A patent/AR077764A1/es unknown
- 2010-07-19 WO PCT/US2010/042423 patent/WO2011011315A1/en not_active Ceased
- 2010-07-19 JP JP2012521703A patent/JP2012533631A/ja active Pending
- 2010-07-19 EP EP10802718A patent/EP2456454A4/en not_active Withdrawn
- 2010-07-19 CA CA2768360A patent/CA2768360A1/en not_active Abandoned
- 2010-07-19 TW TW099123673A patent/TWI557224B/zh active
- 2010-07-19 CN CN2010800332967A patent/CN102470156A/zh active Pending
- 2010-07-19 US US12/838,926 patent/US20110015130A1/en not_active Abandoned
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2012
- 2012-01-08 IL IL217424A patent/IL217424A0/en unknown
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH09512706A (ja) * | 1994-03-28 | 1997-12-22 | サイトメッド， インコーポレイテッド | ＫｉｔリガンドおよびＦＬＴ−３／ＦＬＫ−２リガンドの共有結合二量体 |
| WO2008088548A2 (en) * | 2006-12-26 | 2008-07-24 | National Taiwan University | Disintegrin variants and pharmaceutical uses thereof |
Non-Patent Citations (1)
| Title |
|---|
| JPN6014047541; Ｅｕｒ． Ｊ． Ｐｈａｒｍ． Ｂｉｏｐｈａｒｍ． Ｖｏｌ．７２， Ｎｏ．２, 200906, ｐｐ．４０５-４１１ * |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2017060462A (ja) * | 2015-08-07 | 2017-03-30 | アレキソ セラピューティクス インク． | Ｓｉｒｐ−アルファ変異体構築物及びその使用 |
| JP2021166521A (ja) * | 2015-08-07 | 2021-10-21 | エーエルエックス オンコロジー インコーポレイテッド | Ｓｉｒｐ−アルファ変異体構築物及びその使用 |
| US11208459B2 (en) | 2015-08-07 | 2021-12-28 | ALX Oncology Inc. | Constructs having a SIRP-alpha domain or variant thereof |
| US11639376B2 (en) | 2015-08-07 | 2023-05-02 | ALX Oncology Inc. | Constructs having a SIRP-α domain or variant thereof |
| US11613564B2 (en) | 2019-05-31 | 2023-03-28 | ALX Oncology Inc. | Methods of treating cancer |
| US12527838B2 (en) | 2019-11-27 | 2026-01-20 | ALX Oncology Inc. | Combination therapies comprising an agent that blocks the interaction between CD47 and SIRPα for treating gastric or gastroesphageal junction cancel |
| US12098214B2 (en) | 2021-05-13 | 2024-09-24 | ALX Oncology Inc. | Combination therapies for treating cancer |
Also Published As
| Publication number | Publication date |
|---|---|
| IL217424A0 (en) | 2012-02-29 |
| EP2456454A4 (en) | 2013-03-20 |
| US20110015130A1 (en) | 2011-01-20 |
| RU2547592C2 (ru) | 2015-04-10 |
| TWI557224B (zh) | 2016-11-11 |
| MX2012000895A (es) | 2012-06-01 |
| AU2010276453A1 (en) | 2012-02-09 |
| NZ597580A (en) | 2013-11-29 |
| CA2768360A1 (en) | 2011-01-27 |
| AR077764A1 (es) | 2011-09-21 |
| EP2456454A1 (en) | 2012-05-30 |
| KR20120097481A (ko) | 2012-09-04 |
| WO2011011315A1 (en) | 2011-01-27 |
| TW201107471A (en) | 2011-03-01 |
| CN102470156A (zh) | 2012-05-23 |
| RU2012105915A (ru) | 2013-08-27 |
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