JP6162358B2 - 高分子−第ix因子部分の抱合体 - Google Patents
高分子−第ix因子部分の抱合体 Download PDFInfo
- Publication number
- JP6162358B2 JP6162358B2 JP2011221316A JP2011221316A JP6162358B2 JP 6162358 B2 JP6162358 B2 JP 6162358B2 JP 2011221316 A JP2011221316 A JP 2011221316A JP 2011221316 A JP2011221316 A JP 2011221316A JP 6162358 B2 JP6162358 B2 JP 6162358B2
- Authority
- JP
- Japan
- Prior art keywords
- factor
- conjugate
- moiety
- composition
- poly
- 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.)
- Active
Links
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
- A61K38/482—Serine endopeptidases (3.4.21)
- A61K38/4846—Factor VII (3.4.21.21); Factor IX (3.4.21.22); Factor Xa (3.4.21.6); Factor XI (3.4.21.27); Factor XII (3.4.21.38)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/59—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
- A61K47/60—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/745—Blood coagulation or fibrinolysis factors
- C07K14/755—Factors VIII, e.g. factor VIII C (AHF), factor VIII Ag (VWF)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
- C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
- C12N9/64—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
- C12N9/6421—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
- C12N9/6424—Serine endopeptidases (3.4.21)
- C12N9/644—Coagulation factor IXa (3.4.21.22)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/96—Stabilising an enzyme by forming an adduct or a composition; Forming enzyme conjugates
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y304/00—Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
- C12Y304/21—Serine endopeptidases (3.4.21)
- C12Y304/21022—Coagulation factor IXa (3.4.21.22)
Description
フェニルアラニンは、PheまたはF;ロイシンは、LeuまたはL;イソロイシンは、IleまたはI;メチオニンは、MetまたはM;バリンは、ValまたはV;セリンは、SerまたはS;プロリンは、ProまたはP;スレオニンは、ThrまたはT;アラニンは、AlaまたはA;チロシンは、TyrまたはY;ヒスチジンは、HisまたはH;グルタミン(Glutarnine)は、GlnまたはQ;アスパラギンは、AsnまたはN;リシンは、LysまたはK;アスパラギン酸は、AspまたはD;グルタミン酸は、GluまたはE;システインは、CysまたはC;トリプトファンは、TrpまたはW;アルギニンは、ArgまたはR;グリシンは、GlyまたはG。
polyaおよびpolybは、メトキシポリ(エチレングリコール)のような、(同一の、または異なる)PEG骨格である;
R”は、H、メチル、またはPEG骨格のような非反応性部分である:且つ
PおよびQは、非反応性結合である}。1つ以上の実施態様では、分岐PEG高分子は、メトキシポリ(エチレングリコール)二置換リシンである。使用される特定の第IX因子に依存して、二置換リシンの反応性エステル官能基は、第IX因子部分内のターゲットグループとの反応に好適な官能基を形成するように、さらに改変することが可能である。
(n)は、2乃至3400の値を有する整数である;
Xは、スペーサ部分であり、メチレン(「−CH2−」)、エチレン(「−CH2CH2−」)、およびプロピレン(「−CH2CH2CH2−」)のうちの1つのであることが好ましい;
R1は、有機ラジカルであり、Hまたはメチル(「−CH3」)であることが好ましい;且つ
F9は、第IX因子部分である}。
各(n)は、それぞれ2乃至3400の値を有する整数である;
Xは、スペーサ部分である;
(b)は、2乃至6の値を有する整数である;
(c)は、2乃至6の値を有する整数である;
各発生におけるR2は、それぞれHまたは低級アルキルである;
F9は、第IX因子部分である}。
各(n)は、それぞれ2乃至3400の値を有する整数である;
(a)は、ゼロでまたは1である;
Xは、存在する場合、1つ以上の原子を含むスペーサ部分である;
(b’)は、ゼロまたは1乃至10の値を有する整数である;
(c)は、1乃至10の値を有する整数である;
各発生におけるR2は、それぞれHまたは有機ラジカルである;
各発生におけるR3は、それぞれHまたは有機ラジカルである;且つ
F9は、第IX因子部分である}。
本発明の実施は、特に明記しない限り、従来技術の範囲内にある、有機合成などの従来の技術を用いる。このような技術は、文献において完全に説明される。試薬および物質は、逆に定められていなければ市販のものである。前掲の、J.March、Organic Chamistry:Reactions Mechanisms and Structure、4th Ed.(New York:Wiley−Interscience、1992)を参照のこと。
実施例1
mPEG−SMB(30kDa)による第IX因子のPEG化
(高分子と第IX因子の比率 1:1;エタノールなし)
実施例2
mPEG−SMB(30kDa)による第IX因子のPEG化
(高分子と第IX因子の比率10:1;エタノールなし)
実施例3
分岐mPEG2−N−ヒドロキシスクシンイミド(40kDa)による第IX因子のPEG化
(高分子と第IX因子の比率1:1;エタノールなし)
実施例4
分岐mPEG2−N−ヒドロキシスクシンイミド(40kDa)による第IX因子のPEG化
(高分子と第IX因子の比率10:1;エタノールなし)
実施例5
mPEG−SMB(30kDa)による第IX因子のPEG化
(高分子と第IX因子の比率10:1;エタノールあり)
実施例6
mPEG−SMB(30kDa)による第IX因子のPEG化
(高分子と第IX因子の比率20:1;エタノールあり)
実施例7
分岐mPEG2−N−ヒドロキシスクシンイミド(40kDa)による第IX因子のPEG化
(高分子と第IX因子の比率10:1;エタノールあり)
実施例8
分岐mPEG2−N−ヒドロキシスクシンイミド(40kDa)による第IX因子のPEG化
(高分子と第IX因子の比率20:1;エタノールあり)
実施例9
mPEG−SMB(30kDa)による第IX因子のPEG化
(高分子と第IX因子の比率20:1;エタノールなし)
実施例10
mPEG−SPA(20kDa)による第IX因子のPEG化
(高分子と第IX因子の比率20:1;エタノールなし)
実施例11
mPEG−SPA(20kDa)による第IX因子のPEG化
(高分子と第IX因子の比率40:1;エタノールなし)
実施例12
分岐mPEG−ブチルアルデヒド(20kDa)による第IX因子のPEG化
(高分子と第IX因子の比率10:1;エタノールなし)
実施例13
分岐mPEG−ブチルアルデヒド(20kDa)による第IX因子のPEG化
(高分子と第IX因子の比率20:1;エタノールなし)
実施例14
mPEG−SPA(20kDa)による第IX因子のPEG化
(高分子と第IX因子の比率53:1;エタノールなし)
実施例15
mPEG−SPA(20kDa)による第IX因子のPEG化
(高分子と第IX因子の比率110:1;エタノールなし)
実施例16
分岐mPEG−ブチルアルデヒド(20kDa)による第IX因子のPEG化
(高分子と第IX因子の比率は20:1;エタノールあり)
実施例17
mPEG−SBAによる第IXa因子のPEG化
実施例19
mPEG−KALによるシステイン挿入第IX因子の抱合、20K
実施例20
典型的な第IX因子−PEG抱合体の生体外活性
Claims (35)
- 第IX因子ポリペプチド内に含まれるシステイン残基のチオール基を介して、第IX因子ポリペプチドに共有結合された1又は2の水溶性ポリマーを含む抱合体であって、当該第IX因子ポリペプチドが第IX因子及び第IXa因子から選択され、そして当該第IX因子ポリペプチドが、上記1又は2の水溶性ポリマーが共有結合するところの上記システイン残基を含むように改変される、前記抱合体。
- 前記第IX因子ポリペプチドが第IX因子である、請求項1に記載の抱合体。
- 前記第IX因子ポリペプチドが第IXa因子である、請求項1に記載の抱合体。
- 前記水溶性ポリマーが、ポリ(エチレングリコール)であり、そして前記抱合体がモノPEG化される、請求項2又は3に記載の抱合体。
- 前記水溶性ポリマーが、ポリ(エチレングリコール)であり、そして前記抱合体がジPEG化される、請求項2又は3に記載の抱合体。
- 前記水溶性ポリマーが、6,000ダルトン〜90,000ダルトンの範囲の総重量平均分子量を有する、請求項2又は3に記載の抱合体。
- 前記第IX因子が、グリコシル化されている、請求項1に記載の抱合体。
- 前記第IX因子ポリペプチドがグリコシル化されていない、請求項1に記載の抱合体。
- 前記第IX因子ポリペプチドが、組み替え第IX因子ポリペプチドである、請求項2又は3に記載の抱合体。
- マレイミド末端水溶性ポリマーを、前記システイン残基のチオール基と反応させることにより形成される、請求項2又は3に記載の抱合体。
- チオエーテル結合を介して第IX因子ポリペプチドに共有結合される水溶性ポリマーを含む抱合体であって、当該第IX因子ポリペプチドが、第IX因子及び第IXa因子から選択され、そして当該第IX因子ポリペプチドが、上記水溶性ポリマーがチオエーテル結合を介して共有結合されるところのシステイン残基を含むように改変された前記抱合体。
- 前記第IX因子ポリペプチドが第IX因子である、請求項11に記載の抱合体。
- 前記第IX因子ポリペプチドが第IXa因子である、請求項11に記載の抱合体。
- 前記水溶性ポリマーが、ポリ(エチレングリコール)であり、そして前記抱合体がモノペグ化されている、請求項12に記載の抱合体。
- 前記水溶性ポリマーが、ポリ(エチレングリコール)であり、そして前記抱合体がモノペグ化されている、請求項13に記載の抱合体。
- 複数の請求項4に記載のモノペグ化ポリペプチド抱合体、又は請求項5に記載のジペグ化第IX因子ポリペプチド抱合体を含む組成物。
- 各ポリ(エチレングリコール)が、ヒドロキシ、アルコキシ、置換アルコキシ、アルケンオキシ、置換アルケンオキシ、アルキノキシ、置換アルキノキシ、アリールオキシ及び置換アリールオキシからなる群から選ばれる末端キャップ部分で末端キャップされている、請求項16に記載の組成物。
- 各ポリ(エチレングリコール)がメトキシで末端キャップされている、請求項17に記載の組成物。
- 各ポリ(エチレングリコール)がヒドロキシで末端キャップされている、請求項17に記載の組成物。
- 各ポリ(エチレングリコール)が、5000ダルトン〜150,000ダルトンの範囲の総重量平均分子量を有する、請求項16に記載の組成物。
- 各ポリ(エチレングリコール)が、6,000ダルトン〜100,000ダルトンの範囲の総重量平均分子量を有する、請求項20に記載の組成物。
- 各ポリ(エチレングリコール)が、10,000ダルトン〜85,000ダルトンの範囲の総重量平均分子量を有する、請求項20に記載の組成物。
- 各ポリ(エチレングリコール)が、20,000ダルトン〜85,000ダルトンの範囲の総重量平均分子量を有する、請求項22に記載の組成物。
- 各抱合体が、同一の直線状ポリ(エチレングリコール)を含む、請求項16に記載の組成物。
- 各抱合体が、同一の分岐状ポリ(エチレングリコール)を含む、請求項16に記載の組成物。
- 各抱合体が、組換え第IX因子ポリペプチドを含む、請求項16に記載の組成物。
- 前記組成物が、アルブミンを実質的に伴わない、請求項16に記載の組成物。
- 前記組成物が、第IX因子活性を有さないタンパク質を実質的に含まない、請求項16に記載の組成物。
- 前記組成物が、非共有結合性水溶性ポリマーを実質的に含まない、請求項16に記載の組成物。
- 凍結乾燥形態の、請求項16に記載の組成物。
- 液体形態の、請求項16に記載の組成物。
- 医薬として許容される賦形剤をさらに含む、請求項16に記載の組成物。
- 各抱合体が、第IX因子ポリペプチド及びポリ(エチレングリコール)とのあいだのチオエーテル結合を含む、請求項16に記載の組成物。
- 各抱合体が、第IX因子ポリペプチド及びポリ(エチレングリコール)とのあいだのジスルフィド結合を含む、請求項16に記載の組成物。
- 前記水溶性ポリマーが、ポリ(アルキレンオキシド)、ポリ(ビニルピロリドン)、ポリ(サッカライド)、ポリ(ビニルアルコール)、ポリオキサゾリン、及びポリ(アクリロイルモルフォリン)からなる群から選ばれる、請求項1に記載の抱合体。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US58450504P | 2004-06-30 | 2004-06-30 | |
US60/584,505 | 2004-06-30 |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2007519528A Division JP2008505119A (ja) | 2004-06-30 | 2005-06-30 | 高分子−第ix因子部分の抱合体 |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2017022364A Division JP6585643B2 (ja) | 2004-06-30 | 2017-02-09 | 高分子−第ix因子部分の抱合体 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2012025768A JP2012025768A (ja) | 2012-02-09 |
JP6162358B2 true JP6162358B2 (ja) | 2017-07-12 |
Family
ID=35429498
Family Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2007519528A Pending JP2008505119A (ja) | 2004-06-30 | 2005-06-30 | 高分子−第ix因子部分の抱合体 |
JP2011221316A Active JP6162358B2 (ja) | 2004-06-30 | 2011-10-05 | 高分子−第ix因子部分の抱合体 |
JP2017022364A Active JP6585643B2 (ja) | 2004-06-30 | 2017-02-09 | 高分子−第ix因子部分の抱合体 |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2007519528A Pending JP2008505119A (ja) | 2004-06-30 | 2005-06-30 | 高分子−第ix因子部分の抱合体 |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2017022364A Active JP6585643B2 (ja) | 2004-06-30 | 2017-02-09 | 高分子−第ix因子部分の抱合体 |
Country Status (11)
Country | Link |
---|---|
US (10) | US7579444B2 (ja) |
EP (1) | EP1765411B2 (ja) |
JP (3) | JP2008505119A (ja) |
KR (2) | KR101100059B1 (ja) |
AU (1) | AU2005260763B2 (ja) |
CA (1) | CA2571292C (ja) |
ES (1) | ES2390082T5 (ja) |
IL (1) | IL180115A (ja) |
MX (1) | MXPA06015234A (ja) |
NO (1) | NO342927B1 (ja) |
WO (1) | WO2006005058A2 (ja) |
Families Citing this family (55)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7083787B2 (en) * | 2000-11-15 | 2006-08-01 | Globeimmune, Inc. | Yeast-dendritic cell vaccines and uses thereof |
US7214660B2 (en) | 2001-10-10 | 2007-05-08 | Neose Technologies, Inc. | Erythropoietin: remodeling and glycoconjugation of erythropoietin |
US7173003B2 (en) | 2001-10-10 | 2007-02-06 | Neose Technologies, Inc. | Granulocyte colony stimulating factor: remodeling and glycoconjugation of G-CSF |
US20070026485A1 (en) | 2003-04-09 | 2007-02-01 | Neose Technologies, Inc. | Glycopegylation methods and proteins/peptides produced by the methods |
WO2005012484A2 (en) | 2003-07-25 | 2005-02-10 | Neose Technologies, Inc. | Antibody-toxin conjugates |
US20080305992A1 (en) | 2003-11-24 | 2008-12-11 | Neose Technologies, Inc. | Glycopegylated erythropoietin |
KR101100059B1 (ko) * | 2004-06-30 | 2011-12-29 | 넥타르 테라퓨틱스 | 중합체인자 ix 부분의 접합체 |
AU2014280936B2 (en) * | 2004-06-30 | 2016-12-15 | Nektar Therapeutics | Polymer-factor ix moiety conjugates |
EP1771066A2 (en) | 2004-07-13 | 2007-04-11 | Neose Technologies, Inc. | Branched peg remodeling and glycosylation of glucagon-like peptide-1 glp-1 |
ES2572779T3 (es) | 2004-10-29 | 2016-06-02 | Ratiopharm Gmbh | Remodelación y glucopegilación del Factor de Crecimiento de Fibroblastos (FGF) |
ES2449195T3 (es) | 2005-01-10 | 2014-03-18 | Ratiopharm Gmbh | Factor estimulante de colonias de granulocitos glicopegilado |
EP2386571B1 (en) | 2005-04-08 | 2016-06-01 | ratiopharm GmbH | Compositions and methods for the preparation of protease resistant human growth hormone glycosylation mutants |
JP5335422B2 (ja) | 2005-06-17 | 2013-11-06 | ノボ ノルディスク ヘルス ケア アクチェンゲゼルシャフト | 少なくとも1つの非天然のシステインを含んでいる操作されたタンパク質の選択的な還元および誘導体化 |
US20070105755A1 (en) | 2005-10-26 | 2007-05-10 | Neose Technologies, Inc. | One pot desialylation and glycopegylation of therapeutic peptides |
US20090048440A1 (en) | 2005-11-03 | 2009-02-19 | Neose Technologies, Inc. | Nucleotide Sugar Purification Using Membranes |
EP2213733A3 (en) | 2006-05-24 | 2010-12-29 | Novo Nordisk Health Care AG | Factor IX analogues having prolonged in vivo half life |
US9187532B2 (en) | 2006-07-21 | 2015-11-17 | Novo Nordisk A/S | Glycosylation of peptides via O-linked glycosylation sequences |
CA2659990C (en) | 2006-08-04 | 2016-03-22 | Prolong Pharmaceuticals, Inc. | Polyethylene glycol erythropoietin conjugates |
EP2054521A4 (en) | 2006-10-03 | 2012-12-19 | Novo Nordisk As | METHODS OF PURIFYING CONJUGATES OF POLYPEPTIDES |
NZ577728A (en) * | 2006-12-27 | 2012-01-12 | Baxter Int | Von willebrand factor- and factor viii-polymer conjugates having a releasable linkage |
US8507653B2 (en) * | 2006-12-27 | 2013-08-13 | Nektar Therapeutics | Factor IX moiety-polymer conjugates having a releasable linkage |
WO2008119815A1 (en) * | 2007-04-02 | 2008-10-09 | Novo Nordisk A/S | Subcutaneous administration of coagulation factor ix |
CA2682897C (en) | 2007-04-03 | 2016-11-22 | Biogenerix Ag | Methods of treatment using glycopegylated g-csf |
CN101778859B (zh) | 2007-06-12 | 2014-03-26 | 诺和诺德公司 | 改良的用于生产核苷酸糖的方法 |
EP2209487A4 (en) * | 2007-10-15 | 2012-06-20 | Univ North Carolina | VARIANTS OF HUMAN FACTOR IX WITH EXTENDED HALF-TIME |
US20130189239A1 (en) | 2008-02-27 | 2013-07-25 | Novo Nordisk A/S | Conjugated Factor VIII Molecules |
CA2721362A1 (en) * | 2008-04-16 | 2009-11-19 | Bayer Healthcare Llc | Site-directed modification of factor ix |
NZ588854A (en) * | 2008-04-24 | 2011-12-22 | Celtic Pharma Peg Ltd | Factor ix-polyethylene conjugates with extended half-lives |
WO2010045568A1 (en) * | 2008-10-17 | 2010-04-22 | Baxter International Inc. | Modified blood factors comprising a low degree of water soluble polymer |
GB201007356D0 (en) | 2010-04-30 | 2010-06-16 | Leverton Licence Holdings Ltd | Conjugated factor VIIa |
EP3578205A1 (en) | 2010-08-06 | 2019-12-11 | ModernaTX, Inc. | A pharmaceutical formulation comprising engineered nucleic acids and medical use thereof |
US20120237975A1 (en) | 2010-10-01 | 2012-09-20 | Jason Schrum | Engineered nucleic acids and methods of use thereof |
EP2691101A2 (en) | 2011-03-31 | 2014-02-05 | Moderna Therapeutics, Inc. | Delivery and formulation of engineered nucleic acids |
WO2012167076A2 (en) * | 2011-06-01 | 2012-12-06 | The Regents Of The University Of Michigan | Nanochannel-guided patterning for polymeric substrates |
US9464124B2 (en) | 2011-09-12 | 2016-10-11 | Moderna Therapeutics, Inc. | Engineered nucleic acids and methods of use thereof |
CA2850624A1 (en) | 2011-10-03 | 2013-04-11 | Moderna Therapeutics, Inc. | Modified nucleosides, nucleotides, and nucleic acids, and uses thereof |
KR20140102759A (ko) | 2011-12-16 | 2014-08-22 | 모더나 세라퓨틱스, 인코포레이티드 | 변형된 뉴클레오사이드, 뉴클레오타이드 및 핵산 조성물 |
US9878056B2 (en) | 2012-04-02 | 2018-01-30 | Modernatx, Inc. | Modified polynucleotides for the production of cosmetic proteins and peptides |
US9283287B2 (en) | 2012-04-02 | 2016-03-15 | Moderna Therapeutics, Inc. | Modified polynucleotides for the production of nuclear proteins |
CA2868398A1 (en) | 2012-04-02 | 2013-10-10 | Moderna Therapeutics, Inc. | Modified polynucleotides for the production of cosmetic proteins and peptides |
US9572897B2 (en) | 2012-04-02 | 2017-02-21 | Modernatx, Inc. | Modified polynucleotides for the production of cytoplasmic and cytoskeletal proteins |
EP2838566A2 (en) * | 2012-04-16 | 2015-02-25 | Cantab Biopharmaceuticals Patents Limited | Optimised subcutaneous therapeutic agents |
JP6144355B2 (ja) | 2012-11-26 | 2017-06-07 | モデルナティエックス インコーポレイテッドModernaTX,Inc. | 化学修飾mRNA |
US8980864B2 (en) | 2013-03-15 | 2015-03-17 | Moderna Therapeutics, Inc. | Compositions and methods of altering cholesterol levels |
EP3052106A4 (en) | 2013-09-30 | 2017-07-19 | ModernaTX, Inc. | Polynucleotides encoding immune modulating polypeptides |
JP2016538829A (ja) | 2013-10-03 | 2016-12-15 | モデルナ セラピューティクス インコーポレイテッドModerna Therapeutics,Inc. | 低密度リポタンパク質受容体をコードするポリヌクレオチド |
AU2016324310B2 (en) | 2015-09-17 | 2021-04-08 | Modernatx, Inc. | Compounds and compositions for intracellular delivery of therapeutic agents |
CA3007955A1 (en) | 2015-12-10 | 2017-06-15 | Modernatx, Inc. | Lipid nanoparticles for delivery of therapeutic agents |
PL3394030T3 (pl) | 2015-12-22 | 2022-04-11 | Modernatx, Inc. | Związki i kompozycje do wewnątrzkomórkowego dostarczania środków |
WO2018089540A1 (en) | 2016-11-08 | 2018-05-17 | Modernatx, Inc. | Stabilized formulations of lipid nanoparticles |
EP3596042B1 (en) | 2017-03-15 | 2022-01-12 | Modernatx, Inc. | Crystal forms of amino lipids |
HUE060693T2 (hu) | 2017-03-15 | 2023-04-28 | Modernatx Inc | Vegyület és készítmények terápiás szerek intracelluláris bejuttatására |
US11874480B2 (en) | 2017-12-20 | 2024-01-16 | The Regents Of The University Of Michigan | Plasmonic lithography for patterning high aspect-ratio nanostructures |
JP2022548304A (ja) | 2019-09-19 | 2022-11-17 | モデルナティエックス インコーポレイテッド | 治療薬の細胞内送達のための分岐状尾部脂質化合物及び組成物 |
US11524023B2 (en) | 2021-02-19 | 2022-12-13 | Modernatx, Inc. | Lipid nanoparticle compositions and methods of formulating the same |
Family Cites Families (56)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4179337A (en) * | 1973-07-20 | 1979-12-18 | Davis Frank F | Non-immunogenic polypeptides |
US4361510A (en) * | 1980-05-27 | 1982-11-30 | Cutter Laboratories, Inc. | Blood coagulation promoting product |
US4470968A (en) * | 1983-01-13 | 1984-09-11 | Miles Laboratories, Inc. | Pasteurized therapeutically active blood coagulation factor concentrates |
US5614500A (en) * | 1983-03-04 | 1997-03-25 | The Scripps Research Institute | Compositions containing highly purified factor IX proteins prepared by immunoaffinity chromatography |
JPS59172425A (ja) * | 1983-03-18 | 1984-09-29 | Nippon Chemiphar Co Ltd | 新規な血液凝固因子誘導体およびその製造法ならびにそれを含有する血液凝固促進剤 |
US5171569A (en) * | 1985-03-15 | 1992-12-15 | National Research Development Corporation | Factor IX preparations uncontaminated by plasma components or pox virus |
AU5864086A (en) | 1985-04-22 | 1986-11-18 | Genetics Institute Inc. | High yield production of active factor ix |
US4786726A (en) * | 1986-01-06 | 1988-11-22 | Blood Systems, Inc. | Factor IX therapeutic blood product, means and methods of preparing same |
US5166322A (en) * | 1989-04-21 | 1992-11-24 | Genetics Institute | Cysteine added variants of interleukin-3 and chemical modifications thereof |
ATE158816T1 (de) | 1990-11-26 | 1997-10-15 | Genetics Inst | Expression von pace in wirtszellen und verfahren zu dessen verwendung |
AT402261B (de) * | 1991-01-25 | 1997-03-25 | Immuno Ag | Komplex enthaltend den gerinnungsfaktor ix |
US5595732A (en) * | 1991-03-25 | 1997-01-21 | Hoffmann-La Roche Inc. | Polyethylene-protein conjugates |
US6037452A (en) * | 1992-04-10 | 2000-03-14 | Alpha Therapeutic Corporation | Poly(alkylene oxide)-Factor VIII or Factor IX conjugate |
AU5006993A (en) | 1992-08-21 | 1994-03-15 | Enzon, Inc. | Novel attachment of polyalkylene oxides to bio-effecting substances |
US5298643A (en) * | 1992-12-22 | 1994-03-29 | Enzon, Inc. | Aryl imidate activated polyalkylene oxides |
US5321095A (en) | 1993-02-02 | 1994-06-14 | Enzon, Inc. | Azlactone activated polyalkylene oxides |
US5621039A (en) | 1993-06-08 | 1997-04-15 | Hallahan; Terrence W. | Factor IX- polymeric conjugates |
US5919455A (en) * | 1993-10-27 | 1999-07-06 | Enzon, Inc. | Non-antigenic branched polymer conjugates |
US6372716B1 (en) | 1994-04-26 | 2002-04-16 | Genetics Institute, Inc. | Formulations for factor IX |
US5629384A (en) | 1994-05-17 | 1997-05-13 | Consiglio Nazionale Delle Ricerche | Polymers of N-acryloylmorpholine activated at one end and conjugates with bioactive materials and surfaces |
US5714583A (en) | 1995-06-07 | 1998-02-03 | Genetics Institute, Inc. | Factor IX purification methods |
SE9503380D0 (sv) * | 1995-09-29 | 1995-09-29 | Pharmacia Ab | Protein derivatives |
WO1997018833A1 (en) * | 1995-11-22 | 1997-05-29 | Amgen Inc. | Methods of increasing lean tissue mass using ob protein compositions |
US6320029B1 (en) | 1996-11-29 | 2001-11-20 | The American National Red Cross | Methods of production and use of liquid formulations of plasma proteins |
US5925738A (en) | 1995-12-01 | 1999-07-20 | The American National Red Cross | Methods of production and use of liquid formulations of plasma proteins |
US5770700A (en) | 1996-01-25 | 1998-06-23 | Genetics Institute, Inc. | Liquid factor IX formulations |
US6753165B1 (en) * | 1999-01-14 | 2004-06-22 | Bolder Biotechnology, Inc. | Methods for making proteins containing free cysteine residues |
US6159722A (en) * | 1997-12-03 | 2000-12-12 | Boehringer Mannheim Gmbh | Chimeric serine proteases |
KR100614212B1 (ko) * | 1998-08-06 | 2006-08-21 | 마운틴 뷰 파마슈티컬즈 인크. | 피이지-유레이트 옥시데이즈 접합체 및 그의 이용 |
US6660843B1 (en) * | 1998-10-23 | 2003-12-09 | Amgen Inc. | Modified peptides as therapeutic agents |
CN1810832B (zh) * | 1998-10-23 | 2012-12-12 | 麒麟-安姆根有限公司 | 与MPl受体结合并具有血小板生成活性的模拟二聚体血小板生成素肽 |
US6423626B1 (en) * | 1998-11-02 | 2002-07-23 | Micron Technology, Inc. | Removal of metal cusp for improved contact fill |
KR100619612B1 (ko) * | 1999-10-04 | 2006-09-01 | 넥타르 테라퓨틱스 에이엘, 코포레이션 | 폴리머 안정화 신경펩타이드 |
US7355019B2 (en) * | 2000-06-06 | 2008-04-08 | Sibtech, Inc. | Cysteine-containing peptide tag for site-specific conjugation of proteins |
US6423826B1 (en) | 2000-06-30 | 2002-07-23 | Regents Of The University Of Minnesota | High molecular weight derivatives of vitamin K-dependent polypeptides |
RU2003109746A (ru) * | 2000-09-08 | 2005-01-27 | Грифон Терапьютикс, Инк. (Us) | Синтетические белки, стимулирующие эритропоэз |
JP2002112782A (ja) * | 2000-10-04 | 2002-04-16 | Ajinomoto Co Inc | 抗血栓活性を有する蛋白質及びその製造法 |
DE10112825A1 (de) | 2001-03-16 | 2002-10-02 | Fresenius Kabi De Gmbh | HESylierung von Wirkstoffen in wässriger Lösung |
US7214660B2 (en) * | 2001-10-10 | 2007-05-08 | Neose Technologies, Inc. | Erythropoietin: remodeling and glycoconjugation of erythropoietin |
NZ532027A (en) * | 2001-10-10 | 2008-09-26 | Neose Technologies Inc | Remodeling and glycoconjugation of peptides |
US7125843B2 (en) * | 2001-10-19 | 2006-10-24 | Neose Technologies, Inc. | Glycoconjugates including more than one peptide |
US7179617B2 (en) | 2001-10-10 | 2007-02-20 | Neose Technologies, Inc. | Factor IX: remolding and glycoconjugation of Factor IX |
US7026440B2 (en) * | 2001-11-07 | 2006-04-11 | Nektar Therapeutics Al, Corporation | Branched polymers and their conjugates |
WO2003049760A1 (en) * | 2001-12-07 | 2003-06-19 | Intermune, Inc. | Compositions and method for treating hepatitis virus infection |
US7459435B2 (en) * | 2002-08-29 | 2008-12-02 | Hoffmann-La Roche Inc. | Treatment of disturbances of iron distribution |
US20040106779A1 (en) | 2002-12-03 | 2004-06-03 | Bigler Douglas E. | Modified factor IX preparation |
CA2509260C (en) * | 2002-12-31 | 2012-10-02 | Nektar Therapeutics Al, Corporation | Maleamic acid polymer derivatives and their bioconjugates |
US20040180054A1 (en) | 2003-03-13 | 2004-09-16 | Hanmi Pharm. Co., Ltd. | Physiologically active polypeptide conjugate having prolonged in vivo half-life |
US20050176108A1 (en) | 2003-03-13 | 2005-08-11 | Young-Min Kim | Physiologically active polypeptide conjugate having prolonged in vivo half-life |
US7610156B2 (en) * | 2003-03-31 | 2009-10-27 | Xencor, Inc. | Methods for rational pegylation of proteins |
ES2725808T3 (es) * | 2003-05-23 | 2019-09-27 | Nektar Therapeutics | Derivados de PEG que contienen dos cadenas de PEG |
US7141544B2 (en) * | 2003-10-10 | 2006-11-28 | Baxter International, Inc. | Stabilization of pharmaceutical protein formulations with small peptides |
WO2005055950A2 (en) * | 2003-12-03 | 2005-06-23 | Neose Technologies, Inc. | Glycopegylated factor ix |
AU2005224078B2 (en) * | 2004-03-17 | 2011-01-27 | Anticancer, Inc. | Methods for increasing protein polyethylene glycol (PEG) conjugation |
KR101100059B1 (ko) * | 2004-06-30 | 2011-12-29 | 넥타르 테라퓨틱스 | 중합체인자 ix 부분의 접합체 |
PL1824988T3 (pl) * | 2004-11-12 | 2018-01-31 | Bayer Healthcare Llc | Ukierunkowana na miejsce modyfikacja czynnika VIII |
-
2005
- 2005-06-30 KR KR1020077002327A patent/KR101100059B1/ko active IP Right Grant
- 2005-06-30 EP EP05767845.0A patent/EP1765411B2/en active Active
- 2005-06-30 AU AU2005260763A patent/AU2005260763B2/en active Active
- 2005-06-30 KR KR1020117005370A patent/KR101146160B1/ko active IP Right Grant
- 2005-06-30 ES ES05767845.0T patent/ES2390082T5/es active Active
- 2005-06-30 JP JP2007519528A patent/JP2008505119A/ja active Pending
- 2005-06-30 MX MXPA06015234A patent/MXPA06015234A/es active IP Right Grant
- 2005-06-30 WO PCT/US2005/023745 patent/WO2006005058A2/en active Application Filing
- 2005-06-30 CA CA2571292A patent/CA2571292C/en active Active
- 2005-06-30 US US11/172,459 patent/US7579444B2/en active Active
-
2006
- 2006-12-17 IL IL180115A patent/IL180115A/en active IP Right Grant
-
2007
- 2007-01-29 NO NO20070552A patent/NO342927B1/no unknown
-
2009
- 2009-07-08 US US12/499,770 patent/US20090280550A1/en not_active Abandoned
- 2009-12-15 US US12/638,744 patent/US20100130684A1/en not_active Abandoned
- 2009-12-15 US US12/638,904 patent/US20100130428A1/en not_active Abandoned
- 2009-12-15 US US12/638,811 patent/US8586711B2/en active Active
- 2009-12-15 US US12/638,874 patent/US20100137511A1/en not_active Abandoned
-
2010
- 2010-06-07 US US12/795,461 patent/US20100249033A1/en not_active Abandoned
-
2011
- 2011-10-05 JP JP2011221316A patent/JP6162358B2/ja active Active
-
2013
- 2013-11-08 US US14/076,116 patent/US9347054B2/en active Active
-
2016
- 2016-05-17 US US15/157,343 patent/US20170035896A1/en not_active Abandoned
-
2017
- 2017-02-09 JP JP2017022364A patent/JP6585643B2/ja active Active
-
2020
- 2020-10-05 US US17/063,654 patent/US20210023186A1/en not_active Abandoned
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6585643B2 (ja) | 高分子−第ix因子部分の抱合体 | |
US11141465B2 (en) | Method of making a water-soluble polymer-factor VIII moiety conjugate | |
AU2014280936B2 (en) | Polymer-factor ix moiety conjugates | |
WO2012088123A1 (en) | Polymer-factor vii moiety conjugates | |
AU2012203323A1 (en) | Polymer-factor IX moiety conjugates |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20111104 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20111104 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20130212 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20130513 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20130516 |
|
A711 | Notification of change in applicant |
Free format text: JAPANESE INTERMEDIATE CODE: A711 Effective date: 20130618 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20130809 |
|
RD02 | Notification of acceptance of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7422 Effective date: 20130809 |
|
RD03 | Notification of appointment of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7423 Effective date: 20130902 |
|
RD04 | Notification of resignation of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7424 Effective date: 20130920 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20131022 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20140121 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20140124 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20141028 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20150302 |
|
A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20150507 |
|
A912 | Re-examination (zenchi) completed and case transferred to appeal board |
Free format text: JAPANESE INTERMEDIATE CODE: A912 Effective date: 20150619 |
|
A711 | Notification of change in applicant |
Free format text: JAPANESE INTERMEDIATE CODE: A711 Effective date: 20151228 |
|
RD02 | Notification of acceptance of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7422 Effective date: 20160614 |
|
RD03 | Notification of appointment of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7423 Effective date: 20160614 |
|
RD04 | Notification of resignation of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7424 Effective date: 20160623 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20161109 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20170209 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20170615 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6162358 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |