JP2002505574A - ポリアルキレンオキシド修飾された単鎖ポリペプチド - Google Patents
ポリアルキレンオキシド修飾された単鎖ポリペプチドInfo
- Publication number
- JP2002505574A JP2002505574A JP54734798A JP54734798A JP2002505574A JP 2002505574 A JP2002505574 A JP 2002505574A JP 54734798 A JP54734798 A JP 54734798A JP 54734798 A JP54734798 A JP 54734798A JP 2002505574 A JP2002505574 A JP 2002505574A
- Authority
- JP
- Japan
- Prior art keywords
- antigen
- polypeptide
- binding
- chain
- polyalkylene oxide
- 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
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- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6854—Immunoglobulins
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- 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
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- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
Abstract
Description
Claims (1)
- 【特許請求の範囲】 1.抗原結合単鎖ポリペプチド−ポリアルキレンオキシド結合体であって、以下 : (a)抗体の重鎖または軽鎖の可変領域の抗原結合部分を含む第一のポリペプ チド; (b)抗体の重鎖または軽鎖の可変領域の抗原結合部分を含む第二のポリペプ チド;ならびに (c)該第一のポリペプチド(a)および該第二のポリペプチド(b)を連結 して、抗原結合部位を有する単鎖ポリペプチドにするペプチドリンカー を含む抗原結合単鎖ポリペプチド、を含む結合体であって、 ここで、該抗原結合単鎖ポリペプチドがポリアルキレンオキシドと結合体化さ れ、そして、ここで該抗原結合単鎖ポリペプチド−ポリアルキレンオキシド結合 体が、その結合体化されていない形態における該抗原結合単鎖ポリペプチドの抗 原結合親和性の約1倍〜約10倍の範囲にある抗原結合親和性を有する、 結合体。 2.抗原結合単鎖ポリペプチド−ポリアルキレンオキシド結合体であって、以下 : (a)抗体の重鎖または軽鎖の可変領域の抗原結合部分を含む第一のポリペプ チド; (b)抗体の重鎖または軽鎖の可変領域の抗原結合部分を含む第二のポリペプ チド;ならびに (c)該第一のポリペプチド(a)および該第二のポリペプチド(b)を連結 して、抗原結合部位を有する単鎖ポリペプチドにするペプチドリンカー を含む抗原結合単鎖ポリペプチド、を含む結合体であって、 ここで、該抗原結合単鎖ポリペプチドがポリアルキレンオキシドと結合体化さ れ、そして、ここで、該抗原結合単鎖ポリペプチド−ポリアルキレンオキシド結 合体が、その結合体化されていない形態における該抗原結合単鎖ポリペプチドの 抗原結合親和性の約10倍以内の抗原結合親和性を有する、 結合体。 3.抗原結合単鎖ポリペプチド−ポリアルキレンオキシド結合体であって、以下 : (a)抗体の重鎖または軽鎖の可変領域の抗原結合部分を含む第一のポリペプ チド; (b)抗体の重鎖または軽鎖の可変領域の抗原結合部分を含む第二のポリペプ チド;ならびに (c)該第一のポリペプチド(a)および該第二のポリペプチド(b)を連結 して、抗原結合部位を有する単鎖ポリペプチドにするペプチドリンカー を含む抗原結合単鎖ポリペプチド、を含む結合体であって、 ここで、該抗原結合単鎖ポリペプチドがポリアルキレンオキシドと結合体化さ れ、そして、ここで、該抗原結合単鎖ポリペプチド−ポリアルキレンオキシド結 合体が、その結合体化されていない形態における該抗原結合単鎖ポリペプチドの 抗原結合親和性の約5倍以内の抗原結合親和性を有する、 結合体。 4.抗原結合単鎖ポリペプチド−ポリアルキレンオキシド結合体であって、以下 : (a)抗体の重鎖または軽鎖の可変領域の抗原結合部分を含む第一のポリペプ チド; (b)抗体の重鎖または軽鎖の可変領域の抗原結合部分を含む第二のポリペプ チド;ならびに (c)該第一のポリペプチド(a)および該第二のポリペプチド(b)を連結 して、抗原結合部位を有する単鎖ポリペプチドにするペプチドリンカー を含む抗原結合単鎖ポリペプチド、を含む結合体であって、 ここで、該抗原結合単鎖ポリペプチドがポリアルキレンオキシドと結合体化さ れ、そして、ここで、該抗原結合単鎖ポリペプチド−ポリアルキレンオキシド結 合体が、その結合体化されていない形態における該抗原結合単鎖ポリペプチドの 抗原結合親和性の約2倍以内の抗原結合親和性を有する、 結合体。 5.ポリアルキレンオキシド結合体化をし得る抗原結合単鎖ポリペプチドであっ て、以下: (a)抗体の重鎖または軽鎖の可変領域の抗原結合部分を含む第一のポリペプ チド; (b)抗体の重鎖または軽鎖の可変領域の抗原結合部分を含む第二のポリペプ チド;ならびに (c)該第一のポリペプチド(a)および該第二のポリペプチド(b)を連結 して、抗原結合部位を有する単鎖ポリペプチドにするペプチドリンカー を含む抗原結合単鎖ポリペプチドであって、 ここで、該抗原結合単鎖ポリペプチドが、ボリアルキレンオキシド結合体化を し得る少なくとも1つのCys残基を有し、ここで、該Cys残基が以下: (i)該軽鎖可変領域のアミノ酸11位、12位、13位、14位、または1 5位; (ii)該軽鎖可変領域のアミノ酸77位、78位、または79位; (iii)該重鎖可変領域のアミノ酸11位、12位、13位、14位、また は15位; (iv)該重鎖可変領域のアミノ酸82B位、82C位、または83位; (v)該ペプチドリンカーの任意のアミノ酸位置; (vi)ポリペプチド(a)またはポリペプチド(b)のC末端の近傍;およ び (vii)それらの組合せ、 からなる群から選択される位置に位置し、 ここで、該ポリアルキレンオキシド結合体化された抗原結合単鎖ポリペプチド が抗原に結合し得る、 ポリペプチド。 6.前記ポリアルキレン結合体化をし得るCys残基が以下: (i’)前記軽鎖可変領域のアミノ酸77位; (ii’)前記重鎖可変領域のアミノ酸82B位; (iii’)前記ペプチドリンカーのアミノ酸3位; (iv’)前記ポリペプチド(a)または前記ポリペプチド(b)のC末端の 近傍;および (v’)それらの組合せ、 からなる群から選択される位置に位置する、 請求項5に記載の抗原結合単鎖ポリペプチド。 7.前記第一のポリペプチド(a)が抗体軽鎖の可変領域の抗原結合部分を含み 、そして前記第二のポリペプチド(b)が抗体重鎖の可変領域の抗原結合部分を 含む、請求項5に記載の抗原結合単鎖ポリペプチド。 8.前記第二のポリペプチド(b)のC末端がネイティブなC末端である、請求 項5に記載の抗原結合単鎖ポリペプチド。 9.前記第二のポリペプチド(b)のC末端は、該第二のポリペプチドの残りの N末端アミノ酸残基が、前記ポリアルキレンオキシド結合体化された抗原結合単 鎖ポリペプチドが抗原を結合し得るのに十分であるように、1または複数のアミ ノ酸残基の欠失を含む、請求項5に記載の抗原結合単鎖ポリペプチド。 10.前記第二のポリペプチド(b)のC末端は、前記ポリアルキレンオキシド 結合体化された抗原結合単鎖ポリペプチドが抗原を結合し得るように、1または 複数のアミノ酸残基の付加を含む、請求項5に記載の抗原結合単鎖ポリペプチド 。 11.前記ポリアルキレンオキシド結合体化をし得るCys残基がポリアルキレ ンオキシド部分に結合している、請求項5に記載の抗原結合単鎖ポリペプチド。 12.前記ポリアルキレンオキシド結合体化された抗原結合単鎖ポリペプチドが 、1または複数の、ペプチド、脂質、核酸、薬物、毒素、キレート剤、ホウ素付 加物または検出可能な標識分子に結合体化されている、請求項11に記載のポリ アルキレンオキシド結合体化された抗原結合単鎖ポリペプチド。 13.前記ポリアルキレンオキシド結合体化された抗原結合単鎖ポリペプチドが 、キャリアに結合体化されており、該キャリアが、該キャリアに結合した、1ま たは複数の、ペプチド、脂質、核酸、薬物、毒素、キレート剤、ホウ素付加物ま たは検出可能な標識分子を有する、請求項11に記載のポリアルキレンオキシド 結合体化された抗原結合単鎖ポリペプチド。 14.ポリアルキレンオキシド結合体化をし得る抗原結合単鎖ポリペプチドをコ ードするポリヌクレオチド配列であって、以下: (a)抗体の重鎖または軽鎖の可変領域の抗原結合部分を含む第一のポリペプ チド; (b)抗体の重鎖または軽鎖の可変領域の抗原結合部分を含む第二のポリペプ チド;ならびに (c)該第一のポリペプチド(a)および該第二のポリペプチド(b)を連結 して、抗原結合部位を有する単鎖ポリペプチドにするペプチドリンカー を含む、ポリヌクレオチド配列であって、 ここで、該抗原結合単鎖ポリペプチドが、ポリアルキレンオキシド結合体化を し得る少なくとも1つのCys残基を有し、ここで、該Cys残基が以下: (i)該軽鎖可変領域のアミノ酸11位、12位、13位、14位、または1 5位; (ii)該軽鎖可変領域のアミノ酸77位、78位、または79位; (iii)該重鎖可変領域のアミノ酸11位、12位、13位、14位、また は15位; (iv)該重鎖可変領域のアミノ酸82B位、82C位、または83位; (v)該ペプチドリンカーの任意のアミノ酸位置; (vi)該ポリペプチド(a)または該ポリペプチド(b)のC末端の近傍; および (vii)それらの組合せ、 からなる群から選択される位置に位置し、そして ここで、該ポリアルキレンオキシド結合体化された抗原結合単鎖ポリペプチド が抗原に結合し得る、 ポリヌクレオチド配列。 15.前記ポリアルキレンオキシド結合体化をし得るCys残基が以下: (i’)前記軽鎖可変領域のアミノ酸77位; (ii’)前記重鎖可変領域のアミノ酸82B位; (iii’)前記ペプチドリンカーのアミノ酸3位; (iv’)前記ポリペプチド(a)または前記ポリペプチド(b)のC末端の 近傍;および (v’)それらの組合せ、 からなる群から選択される位置に位置する、 請求項14に記載のポリヌクレオチド配列。 16.請求項14に記載のポリヌクレオチド配列を含む、複製可能なクローニン グまたは発現ビヒクル。 17.プラスミドである、請求項16に記載のビヒクル。 18.請求項17に記載のポリヌクレオチドで形質転換した、宿主細胞。 19.細菌細胞、酵母細胞もしくは他の真菌細胞、昆虫細胞、または哺乳動物細 胞株である、請求項18に記載の宿主細胞。 20.Pichia pastorisである、請求項19に記載の宿主細胞。 21.抗原結合単鎖ポリペプチドを含む、抗原結合単鎖ポリペプチド−ポリアル キレンオキシド結合体を産生する方法であって、以下の工程: (a)抗体の重鎖または軽鎖の可変領域の抗原結合部分を含む第一のポリペプ チドをコードする第一の遺伝的配列を提供する工程; (b)抗体の重鎖または軽鎖の可変領域の抗原結合部分を含む第二のポリペプ チドをコードする第二の遺伝的配列を提供する工程;ならびに (c)該第一の遺伝的配列(a)および該第二の遺伝的配列(b)を、リンカ ーをコードする第三の遺伝的配列と連結して、抗原結合部位を有する単鎖ポリペ プチドをコードする第四の遺伝的配列にする工程、 を包含し、 ここで、該抗原結合単鎖ポリペプチドは、ポリアルキレンオキシド結合体化が され得、そして、 ここで、該抗原結合単鎖ポリペプチド−ポリアルキレンオキシド結合体が、そ の結合体化されていない形態における該抗原結合単鎖ポリペプチドの抗原結合親 和性の約1倍〜約10倍の範囲にある抗原結合親和性を保持する、 方法。 22.ポリアルキレンオキシド結合体化をし得る抗原結合単鎖ポリペプチドを産 生する方法であって、以下の工程: (a)抗体の重鎖または軽鎖の可変領域の抗原結合部分を含む第一のポリペプ チドをコードする第一の遺伝的配列を提供する工程; (b)抗体の重鎖または軽鎖の可変領域の抗原結合部分を含む第二のポリペプ チドをコードする第二の遺伝的配列を提供する工程;ならびに (c)該第一の遺伝的配列(a)および該第二の遺伝的配列(b)を、ペプチ ドリンカーをコードする第三の遺伝的配列と連結して、抗原結合部位を有する単 鎖ポリペプチドをコードする第四の遺伝的配列にする工程であって、 ここで、該抗原結合単鎖ポリペプチドがポリアルキレンオキシド結合体化をし 得る少なくとも1つのCys残基を有し、ここで、該Cys残基が以下: (i)該軽鎖可変領域のアミノ酸11位、12位、13位、14位、または1 5位; (ii)該軽鎖可変領域のアミノ酸77位、78位、または79位; (iii)該重鎖可変領域のアミノ酸11位、12位、13位、14位、また は15位; (iv)該重鎖可変領域のアミノ酸82B位、82C位、または83位; (v)該ペプチドリンカーの任意のアミノ酸位置; (vi)該ポリペプチド(a)または該ポリペプチド(b)のC末端の近傍; および (vii)それらの組合せ、 からなる群から選択される位置に位置し、そして ここで、該ポリアルキレンオキシド結合体化された抗原結合単鎖ポリペプチド が抗原に結合し得る、工程; (d)工程(c)の該抗原結合単鎖ポリペプチドをコードする該第四の遺伝的 配列で宿主細胞を形質転換する工程;ならびに (e)工程(c)の該抗原結合単鎖ポリペプチドを該宿主において発現させて 、それにより、ポリアルキレンオキシド結合体化をし得る抗原結合単鎖ポリペプ チドを産生する工程、 を包含する、方法。 23.前記ポリアルキレンオキシド結合体化をし得るCys残基が以下: (i’)前記軽鎖可変領域のアミノ酸77位; (ii’)前記重鎖可変領域のアミノ酸82B位; (iii’)前記ペプチドリンカーのアミノ酸3位; (iv’)前記ポリペプチド(a)または前記ポリペプチド(b)のC末端の 近傍;および (v’)それらの組合せ、 からなる群から選択される位置に位置する、 請求項22に記載の方法。 24.第一のポリペプチド(a)をコードする前記第一の遺伝的配列が、抗体軽 鎖の可変領域の抗原結合部分を含み、そして前記第二のポリペプチド(b)をコ ードする第二の遺伝的配列が、抗体重鎖の可変領域の抗原結合部分を含む、請求 項22に記載の方法。 25.前記第二のポリペプチド(b)のC末端がネイティブなC末端である、請 求項22に記載の方法。 26.前記第二のポリペプチド(b)のC末端は、該第二のポリペプチドの残り のN末端アミノ酸残基が、前記ポリアルキレンオキシド結合体化された抗原結合 単鎖ポリペプチドが抗原を結合し得るのに十分であるように、1または複数のア ミノ酸残基の欠失を含む、請求項22に記載の方法。 27.前記第二のポリペプチド(b)のC末端は、前記ポリアルキレンオキシド 結合体化された抗原結合単鎖ポリペプチドが抗原を結合し得るように、1または 複数のアミノ酸残基の付加を含む、請求項22に記載の方法。 28.2以上の抗原結合単鎖ポリペプチドを含む多価抗原結合単鎖ポリペプチド ポリアルキレンオキシド結合体であって、該抗原結合単鎖ポリペプチドの各々が 以下: (a)抗体の重鎖または軽鎖の可変領域の抗原結合部分を含む第一のポリペプ チド; (b)抗体の重鎖または軽鎖の可変領域の抗原結合部分を含む第二のポリペプ チド;ならびに (c)該第一のポリペプチド(a)および該第二のポリペプチド(b)を連結 して、抗原結合部位を有する単鎖ポリペプチドにするペプチドリンカー を含み、 ここで、該抗原結合単鎖ポリペプチドがポリアルキレンオキシドと結合体化さ れ、そして、ここで、該抗原結合単鎖ポリペプチド−ポリアルキレンオキシド結 合体が、その結合体化されていない形態における該抗原結合単鎖ポリペプチドの 抗原結合親和性の約1倍〜約10倍の範囲にある抗原結合親和性を保持する、 結合体。 29.2以上の抗原結合単鎖ポリペプチドを含む多価抗原結合単鎖タンパク質で あって、該抗原結合単鎖ポリペプチドの各々が以下: (a)抗体の重鎖または軽鎖の可変領域の抗原結合部分を含む第一のポリペプ チド; (b)抗体の重鎖または軽鎖の可変領域の抗原結合部分を含む第二のポリペプ チド;ならびに (c)該第一のポリペプチドおよび該第二のポリペプチドを連結するペプチド リンカー を含み、 ここで、2つのうちの1つの抗原結合単鎖ポリペプチドが、ポリアルキレンオ キシド結合体化をし得る少なくとも1つのCys残基を有し、ここで、該Cys 残基が以下: (i)該軽鎖可変領域のアミノ酸11位、12位、13位、14位、または1 5位; (ii)該軽鎖可変領域のアミノ酸77位、78位、または79位; (iii)該重鎖可変領域のアミノ酸11位、12位、13位、14位、また は15位; (iv)該重鎖可変領域のアミノ酸82B位、82C位、または83位; (v)該ペプチドリンカーの任意のアミノ酸位置; (vi)該ポリペプチド(a)または該ポリペプチド(b)のC末端の近傍; および (vii)それらの組合せ、 からなる群から選択される位置に位置し、そして ここで、該ポリアルキレンオキシド結合体化された抗原結合単鎖ポリペプチド が抗原に結合し得る、 多価タンパク質。 30.前記ポリアルキレンオキシド結合体化をし得るCys残基が以下: (i’)前記軽鎖可変領域のアミノ酸77位; (ii’)前記重鎖可変領域のアミノ酸82B位; (iii’)前記ペプチドリンカーのアミノ酸3位; (iv’)前記ポリペプチド(a)または前記ポリペプチド(b)のC末端の 近傍;および (v’)それらの組合せ、 からなる群から選択される位置に位置する、 請求項29に記載の多価タンパク質。 31.前記第一のポリペプチド(a)が、抗体軽鎖の可変領域の抗原結合部分を 含み、そして前記第二のポリペプチド(b)が、抗体重鎖の可変領域の抗原結合 部分を含む、請求項29に記載の多価タンパク質。 32.前記第二のポリペプチド(b)のC末端がネイティブなC末端である、請 求項29に記載の多価タンパク質。 33.前記第二のポリペプチド(b)のC末端は、該第二のポリペプチドの残り のN末端アミノ酸残基が、前記ポリアルキレンオキシド結合体化された抗原結合 単鎖ポリペプチドが抗原を結合し得るのに十分であるように、1または複数のア ミノ酸残基の欠失を含む、請求項29に記載の多価タンパク質。 34.前記第二のポリペプチドのC末端は、前記ポリアルキレンオキシド結合体 化された抗原結合単鎖ポリペプチドが抗原を結合し得るように、1または複数の アミノ酸残基の付加を含む、請求項29に記載の多価タンパク質。 35.前記ポリアルキレンオキシド結合体化をし得るCys残基が、ポリアルキ レンオキシド部分に結合している、請求項29に記載の多価タンパク質。 36.前記ポリアルキレンオキシド結合体化された多価タンパク質が、1または 複数の、ペプチド、脂質、核酸、薬物、毒素、キレート剤、ホウ素付加物または 検出可能な標識分子に結合体化されている、請求項35に記載のポリアルキレン オキシド結合体化された多価タンパク質。 37.サンプル中に存在すると疑われる抗原を検出する方法であって、以下の工 程: (a)請求項1または11に記載のポリアルキレンオキシド結合体化されたポ リペプチドまたはタンパク質と該サンプルとを接触させる工程であって、ここで 、該ポリアルキレンオキシド結合体化されたポリペプチドまたはタンパク質は、 1もしくは複数の検出可能な標識分子と結合体化されているか、またはキャリア と結合体化されており、該キャリアは、該キャリアに結合した1または複数の検 出可能な標識分子を有する、工程;ならびに (b)該ポリアルキレンオキシド結合体化された抗原結合単鎖ポリペプチドま たはタンパク質が該抗原に結合したか否かを検出する工程、 を包含する方法。 38.動物の内部構造を画像化する方法であって、以下の工程: 該動物に、請求項1または11に記載のポリアルキレンオキシド結合体化され たポリペプチドまたはタンパク質の有効量を投与する工程であって、ここで、該 ポリアルキレンオキシド結合体化されたポリペプチドまたはタンパク質は、1も しくは複数の検出可能な標識分子またはキレート剤分子と結合体化されているか 、またはキャリアと結合体化されており、該キャリアは、該キャリアに結合した 1または複数の検出可能な標識分子またはキレート剤分子を有する、工程;およ び 該動物に関連する検出可能な放射線を測定する工程、 を包含する、方法。 39.前記動物がヒトを含む、請求項38に記載の方法。 40.標的化された疾患を処置するための方法であって、以下の工程: 請求項1または11に記載のポリアルキレンオキシド結合体化されたポリペプ チドまたはタンパク質および薬学的に受容可能なキャリアビヒクルを含む組成物 の有効量を投与する工程であって、ここで、該ポリアルキレンオキシド結合体化 されたポリペプチドまたはタンパク質は、1または複数の、ペプチド、脂質、核 酸、薬物、毒素、ホウ素付加物または放射性同位体分子に結合体化されているか 、またはキャリアと結合体化されており、該キャリアが、該キャリアに結合した 、1または複数の、ペプチド、脂質、核酸、薬物、毒素、ホウ素付加物または放 射性同位体分子を有する、工程、 を包含する方法。 41.ポリアルキレンオキシド結合体化をし得る抗原結合単鎖ポリペプチドであ って、以下: (a)抗体の重鎖または軽鎖の可変領域の抗原結合部分を含む第一のポリペプ チド; (b)抗体の重鎖または軽鎖の可変領域の抗原結合部分を含む第二のポリペプ チド;ならびに (c)該第一のポリペプチド(a)および該第二のポリペプチド(b)を連結 して、抗原結合部位を有する単鎖ポリペプチドにするペプチドリンカー を含み、 ここで、該抗原結合単鎖ポリペプチドが、ポリアルキレンオキシド結合体化を し得る少なくとも3つの連続するLys残基を有し、そしてここで、該連続する Lys残基の任意の1つが以下: (i)該ペプチドリンカーの任意のアミノ酸位置; (ii)該第二のポリペプチド(b)のC末端の近傍;および (iii)それらの組合せ、 からなる群から選択される位置に位置し、 ここで、該ポリアルキレンオキシド結合体化された抗原結合単鎖ポリペプチド が抗原に結合し得る、 ポリペプチド。 42.ポリアルキレンオキシド結合体化をし得る抗原結合単鎖ポリペプチドをコ ードするポリヌクレオチド配列であって、以下: (a)抗体の重鎖または軽鎖の可変領域の抗原結合部分を含む第一のポリペプ チド; (b)抗体の重鎖または軽鎖の可変領域の抗原結合部分を含む第二のポリペプ チド;ならびに (c)該第一のポリペプチド(a)および該第二のポリペプチド(b)を連結 して、抗原結合部位を有する単鎖ポリペプチドにするペプチドリンカー を含み、 ここで、該抗原結合単鎖ポリペプチドが、ポリアルキレンオキシド結合体化を し得る少なくとも3つの連続するLys残基を有し、そしてここで、該連続する Lys残基のうちの任意の1つが以下: (i)該ペプチドリンカーの任意のアミノ酸位置; (ii)該第二のポリペプチド(b)のC末端の近傍;および (iii)それらの組合せ、 からなる群から選択される位置に位置し、 ここで、該ポリアルキレンオキシド結合体化された抗原結合単鎖ポリペプチド が抗原に結合し得る、 ポリヌクレオチド配列。 43.請求項42に記載のポリヌクレオチド配列を含む、複製可能なクローニン グまたは発現ビヒクル。 44.プラスミドである、請求項43に記載のビヒクル。 45.請求項42に記載のポリヌクレオチドで形質転換した、宿主細胞。 46.細菌細胞、酵母細胞もしくは他の真菌細胞、昆虫細胞、もしくは哺乳動物 細胞株である、請求項39に記載の宿主細胞。 47.Pichia pastorisである、請求項46に記載の宿主細胞。 48.ポリアルキレンオキシド結合体化をし得る抗原結合単鎖ポリペプチドを産 生する方法であって、該ポリペプチドが以下: (a)抗体の重鎖または軽鎖の可変領域の抗原結合部分を含む第一のポリペプ チド; (b)抗体の重鎖または軽鎖の可変領域の抗原結合部分を含む第二のポリペプ チド;ならびに (c)該第一のポリペプチド(a)および該第二のポリペプチド(b)を連結 して、抗原結合部位を有する単鎖ポリペプチドにするペプチドリンカー を含み、 ここで、該抗原結合単鎖ポリペプチドが、ポリアルキレンオキシド結合体化を し得る少なくとも3つの連続するLys残基を有し、そしてここで、該連続する Lys残基のうちの任意の1つが以下: (i)該ペプチドリンカーの任意のアミノ酸位置; (ii)該第二のポリペプチド(b)のC末端の近傍;および (iii)それらの組合せ、 からなる群から選択される位置に位置し、 ここで、該ポリアルキレンオキシド結合体化された抗原結合単鎖ポリペプチド が抗原に結合し得る、 方法。 49.前記ポリアルキレンオキシド結合体化をし得る連続するLys残基のうち の任意の1つが、ポリアルキレンオキシド部分に結合している、請求項41に記 載の抗原結合単鎖ポリペプチド。 50.前記ポリアルキレンオキシド結合体化された抗原結合単鎖ポリペプチドが 、1または複数の、ペプチド、脂質、核酸、薬物、毒素、キレート剤、ホウ素付 加物または検出可能な標識分子に結合体化されている、請求項49に記載のポリ アルキレンオキシド結合体化された抗原結合単鎖ポリペプチド。 51.前記ポリアルキレンオキシド結合体化された抗原結合単鎖ポリペプチドが 、キャリアに結合体化されており、該キャリアが、該キャリアに結合した、1ま たは複数の、ペプチド、脂質、核酸、薬物、毒素、キレート剤、ホウ素付加物ま たは検出可能な標識分子を有する、請求項49に記載のポリアルキレンオキシド 結台体化された抗原結合単鎖ポリペプチド。 52.ポリアルキレンオキシド結合体化をし得る抗原結合単鎖ポリペプチドを産 生する方法であって、以下の工程: (a)抗体の重鎖または軽鎖の可変領域の抗原結合部分を含む第一のポリペプ チドをコードする第一の遺伝的配列を提供する工程; (b)抗体の重鎖または軽鎖の可変領域の抗原結合部分を含む第二のポリペプ チドをコードする第二の遺伝的配列を提供する工程;ならびに (c)該第一の遺伝的配列(a)および該第二の遺伝的配列(b)を、ペプチ ドリンカーをコードする第三の遺伝的配列と連結して、抗原結合部位を有する単 鎖ポリペプチドをコードする第四の遺伝的配列にする工程であって、 ここで、該抗原結合単鎖ポリペプチドが、ポリアルキレンオキシド結合体化を し得る少なくとも3つの連続するLys残基を有し、そしてここで、該連続する Lys残基のうちの任意の1つが以下: (i)該ペプチドリンカーの任意のアミノ酸位置; (ii)該第二のポリペプチド(b)のC末端の近傍;および (iii)それらの組合せ、 からなる群から選択される位置に位置し、 ここで、該ポリアルキレンオキシド結合体化された抗原結合単鎖ポリペプチド が抗原に結合し得る、工程; (d)工程(c)の該抗原結合単鎖ポリペプチドをコードする該第四の遺伝的 配列で宿主細胞を形質転換する工程;ならびに (e)工程(c)の該抗原結合単鎖ポリペプチドを該宿主において発現させて 、それにより、ポリアルキレンオキシド結合体化をし得る抗原結合単鎖ポリペプ チドを産生する工程、 を包含する、方法。 53.第一のポリペプチド(a)をコードする前記第一の遺伝的配列が、抗体軽 鎖の可変領域の抗原結合部分を含み、そして第二のポリペプチド(b)をコード する前記第二の遺伝的配列が、抗体重鎖の可変領域の抗原結合部分を含む、請求 項52に記載の方法。 54.前記第二のポリペプチド(b)のC末端がネイティブなC末端である、請 求項52に記載の方法。 55.前記第二のポリペプチド(b)のC末端は、該第二のポリペプチドの残り のN末端アミノ酸残基が、前記ポリアルキレンオキシド結合体化された抗原結合 単鎖ポリペプチドが抗原を結合し得るのに十分であるように、1または複数のア ミノ酸残基の欠失を含む、請求項52に記載の方法。 56.前記第二のポリペプチド(b)のC末端は、前記ポリアルキレンオキシド 結合体化された抗原結合単鎖ポリペプチドが抗原を結合し得るように、1または 複数のアミノ酸残基の付加を含む、請求項52に記載の方法。 57.2以上の抗原結合単鎖ポリペプチドを含む多価抗原結合単鎖タンパク質で あって、該抗原結合単鎖ポリペプチドの各々が以下: (a)抗体の重鎖または軽鎖の可変領域の抗原結合部分を含む第一のポリペプ チド; (b)抗体の重鎖または軽鎖の可変領域の抗原結合部分を含む第二のポリペプ チド;ならびに (c)該第一のポリペプチド(a)および該第二のポリペプチド(b)を連結 するペプチドリンカー を含み、 ここで、2つのうちの1つの抗原結合単鎖ポリペプチドが、ポリアルキレンオ キシド結合体化をし得る少なくとも3つの連続するLys残基を有し、そしてこ こで、該連続するLys残基のうちの任意の1つが以下: (i)該ペプチドリンカーの任意のアミノ酸位置; (ii)該第二のポリペプチド(b)のC末端の近傍;および (iii)それらの組合せ、 からなる群から選択される位置に位置し、 ここで、該ポリアルキレンオキシド結合体化された抗原結合単鎖ポリペプチド が抗原に結合し得る、 多価タンパク質。 58.前記第一のポリペプチド(a)が、抗体軽鎖の可変領域の抗原結合部分を 含み、そして前記第二のポリペプチド(b)が、抗体重鎖の可変領域の抗原結合 部分を含む、請求項57に記載の多価タンパク質。 59.前記第二のポリペプチド(b)のC末端がネイティブなC末端である、請 求項57に記載の多価タンパク質。 60.前記第二のポリペプチド(b)のC末端は、該第二のポリペプチドの残り のN末端アミノ酸残基が、前記ポリアルキレンオキシド結合体化された抗原結合 単鎖ポリペプチドが抗原を結合し得るのに十分であるように、1または複数のア ミノ酸残基の欠失を含む、請求項57に記載の多価タンパク質。 61.前記第二のポリペプチドのC末端は、前記ポリアルキレンオキシド結合体 化された抗原結合単鎖ポリペプチドが抗原を結合し得るように、1または複数の アミノ酸残基の付加を含む、請求項57に記載の多価タンパク質。 62.ボリアルキレンオキシド結合体化をし得る前記連続するLys残基の任意 の1つが、ポリアルキレンオキシド部分に結合している、請求項57に記載の多 価タンパク質。 63.前記ポリアルキレンオキシド結合体化された多価タンパク質が、1または 複数の、ペプチド、脂質、核酸、薬物、毒素、キレート剤、ホウ素付加物または 検出可能な標識分子に結合体化されている、請求項62に記載のポリアルキレン オキシド結合体化された多価タンパク質。
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
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Families Citing this family (363)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2288994C (en) | 1997-04-30 | 2011-07-05 | Enzon, Inc. | Polyalkylene oxide-modified single chain polypeptides |
US20040009166A1 (en) * | 1997-04-30 | 2004-01-15 | Filpula David R. | Single chain antigen-binding polypeptides for polymer conjugation |
US6333396B1 (en) | 1998-10-20 | 2001-12-25 | Enzon, Inc. | Method for targeted delivery of nucleic acids |
AU768295B2 (en) * | 1998-11-03 | 2003-12-04 | Centocor Inc. | Modified antibodies and antibody fragments with increased duration of activity |
US6610286B2 (en) | 1999-12-23 | 2003-08-26 | Zymogenetics, Inc. | Method for treating inflammation using soluble receptors to interleukin-20 |
US7122632B2 (en) | 1999-12-23 | 2006-10-17 | Zymogenetics, Inc. | Soluble Interleukin-20 receptor |
SK11672002A3 (sk) | 2000-01-10 | 2002-12-03 | Maxygen Holdings Ltd. | Polypeptidový konjugát, spôsob jeho výroby, farmaceutický prostriedok s jeho obsahom a jeho použitie |
JP2003521930A (ja) | 2000-02-11 | 2003-07-22 | マキシゲン・エイピーエス | 第VII因子または第VIIa因子様分子 |
US20030027207A1 (en) * | 2000-02-29 | 2003-02-06 | Filpula David Ray | Anti-platelet binding proteins and polymer conjugates containing the same |
US6410246B1 (en) * | 2000-06-23 | 2002-06-25 | Genetastix Corporation | Highly diverse library of yeast expression vectors |
US6410271B1 (en) * | 2000-06-23 | 2002-06-25 | Genetastix Corporation | Generation of highly diverse library of expression vectors via homologous recombination in yeast |
CZ2003678A3 (cs) * | 2000-09-08 | 2004-03-17 | Gryphon Therapeutics, Inc. | Syntetické proteiny stimulující erytropoézu |
US7118737B2 (en) * | 2000-09-08 | 2006-10-10 | Amylin Pharmaceuticals, Inc. | Polymer-modified synthetic proteins |
US8110218B2 (en) * | 2000-11-30 | 2012-02-07 | The Research Foundation Of State University Of New York | Compositions and methods for less immunogenic protein-lipid complexes |
AU2002223350A1 (en) * | 2000-12-01 | 2002-06-11 | Eleanor N. Fish | Cytokine receptor binding peptides |
US6979556B2 (en) | 2000-12-14 | 2005-12-27 | Genentech, Inc. | Separate-cistron contructs for secretion of aglycosylated antibodies from prokaryotes |
US7195923B2 (en) * | 2001-01-31 | 2007-03-27 | Scripps Laboratories, Inc. | Ratiometric determination of glycated protein |
EP2080771A3 (en) | 2001-02-27 | 2010-01-06 | Maxygen Aps | New interferon beta-like molecules |
KR100968664B1 (ko) | 2001-08-27 | 2010-07-06 | 제넨테크, 인크. | 항체 발현 및 조립을 위한 시스템 |
US7795210B2 (en) * | 2001-10-10 | 2010-09-14 | Novo Nordisk A/S | Protein remodeling methods and proteins/peptides produced by the methods |
US7214660B2 (en) | 2001-10-10 | 2007-05-08 | Neose Technologies, Inc. | Erythropoietin: remodeling and glycoconjugation of erythropoietin |
US8008252B2 (en) | 2001-10-10 | 2011-08-30 | Novo Nordisk A/S | Factor VII: remodeling and glycoconjugation of Factor VII |
US7173003B2 (en) | 2001-10-10 | 2007-02-06 | Neose Technologies, Inc. | Granulocyte colony stimulating factor: remodeling and glycoconjugation of G-CSF |
US7157277B2 (en) | 2001-11-28 | 2007-01-02 | Neose Technologies, Inc. | Factor VIII remodeling and glycoconjugation of Factor VIII |
WO2003051384A1 (en) | 2001-12-17 | 2003-06-26 | Zymogenetics, Inc. | Method for treating cervical cancer |
WO2003062278A1 (en) | 2002-01-25 | 2003-07-31 | G2 Therapies Ltd | MONOCLONAL ANTIBODIES AGAINST EXTRACELLULAR LOOPS OF C5aR |
WO2004000366A1 (en) | 2002-06-21 | 2003-12-31 | Novo Nordisk Health Care Ag | Pegylated factor vii glycoforms |
MXPA04012496A (es) | 2002-06-21 | 2005-09-12 | Novo Nordisk Healthcare Ag | Glicoformos del factor vii pegilados. |
US9321832B2 (en) | 2002-06-28 | 2016-04-26 | Domantis Limited | Ligand |
US20050026866A1 (en) * | 2002-08-02 | 2005-02-03 | Pawelek John M. | Agents and methods for treatment of disease by oligosaccharide targeting agents |
US20040067532A1 (en) | 2002-08-12 | 2004-04-08 | Genetastix Corporation | High throughput generation and affinity maturation of humanized antibody |
AU2003262845A1 (en) * | 2002-08-28 | 2004-03-19 | Millipore Corporation | Compositions of solution for sequencing reaction clean-up |
US8129330B2 (en) | 2002-09-30 | 2012-03-06 | Mountain View Pharmaceuticals, Inc. | Polymer conjugates with decreased antigenicity, methods of preparation and uses thereof |
US20040062748A1 (en) * | 2002-09-30 | 2004-04-01 | Mountain View Pharmaceuticals, Inc. | Polymer conjugates with decreased antigenicity, methods of preparation and uses thereof |
US8034900B2 (en) | 2002-12-30 | 2011-10-11 | Amylin Pharmaceuticals, Inc. | Water-soluble thioester and selenoester compounds and methods for making and using the same |
US20040229793A1 (en) * | 2003-02-05 | 2004-11-18 | Balasubramanian Sathyamangalam V. | Compositions and methods for less immunogenic protein formulations |
US7351688B2 (en) * | 2003-02-05 | 2008-04-01 | The Research Foundation Of State University Of New York | Compositions and methods for less immunogenic protein formulations |
JP2006523211A (ja) | 2003-03-14 | 2006-10-12 | ネオス テクノロジーズ インコーポレイテッド | 分岐水溶性ポリマーとその複合物 |
EP1615945B1 (en) | 2003-04-09 | 2011-09-28 | BioGeneriX AG | Glycopegylation methods and proteins/peptides produced by the methods |
US8791070B2 (en) | 2003-04-09 | 2014-07-29 | Novo Nordisk A/S | Glycopegylated factor IX |
CA2524936A1 (en) * | 2003-05-09 | 2004-12-02 | Neose Technologies, Inc. | Compositions and methods for the preparation of human growth hormone glycosylation mutants |
US9005625B2 (en) * | 2003-07-25 | 2015-04-14 | Novo Nordisk A/S | Antibody toxin conjugates |
US20050069578A1 (en) * | 2003-08-05 | 2005-03-31 | Balasubramanian Sathyamangalam V. | Reconstitution medium for protein and peptide formulations |
US20050055024A1 (en) * | 2003-09-08 | 2005-03-10 | James Anthony H. | Orthopaedic implant and screw assembly |
DE602004029173D1 (de) | 2003-10-10 | 2010-10-28 | Novo Nordisk As | Il-21-derivate |
EP2641611A3 (en) | 2003-10-17 | 2013-12-18 | Novo Nordisk A/S | Combination therapy |
WO2005052000A2 (en) * | 2003-11-21 | 2005-06-09 | Zymogenetics, Inc. | Anti-il-20 antibodies and binding partners and methods of using in inflammation |
US8633157B2 (en) | 2003-11-24 | 2014-01-21 | Novo Nordisk A/S | Glycopegylated erythropoietin |
US20080305992A1 (en) | 2003-11-24 | 2008-12-11 | Neose Technologies, Inc. | Glycopegylated erythropoietin |
US7956032B2 (en) | 2003-12-03 | 2011-06-07 | Novo Nordisk A/S | Glycopegylated granulocyte colony stimulating factor |
US20060040856A1 (en) | 2003-12-03 | 2006-02-23 | Neose Technologies, Inc. | Glycopegylated factor IX |
AU2004296376B2 (en) | 2003-12-05 | 2010-03-04 | Bristol-Myers Squibb Company | Inhibitors of type 2 vascular endothelial growth factor receptors |
US20080220049A1 (en) * | 2003-12-05 | 2008-09-11 | Adnexus, A Bristol-Myers Squibb R&D Company | Compositions and methods for intraocular delivery of fibronectin scaffold domain proteins |
EP1765853B1 (en) | 2004-01-08 | 2015-10-28 | ratiopharm GmbH | O-linked glycosylation of G-CSF peptides |
GB2429207A (en) | 2004-02-02 | 2007-02-21 | Ambrx Inc | Modified human interferon polypeptides and their uses |
JP2008503217A (ja) | 2004-06-18 | 2008-02-07 | アンブレツクス・インコーポレイテツド | 新規抗原結合ポリペプチド及びそれらの使用 |
WO2006010143A2 (en) | 2004-07-13 | 2006-01-26 | Neose Technologies, Inc. | Branched peg remodeling and glycosylation of glucagon-like peptide-1 [glp-1] |
US20090292110A1 (en) * | 2004-07-23 | 2009-11-26 | Defrees Shawn | Enzymatic modification of glycopeptides |
US20060045866A1 (en) * | 2004-09-01 | 2006-03-02 | Chris Chappelow | Novel high purity and high molecular weight mPEG alcohol compositions |
US8268967B2 (en) | 2004-09-10 | 2012-09-18 | Novo Nordisk A/S | Glycopegylated interferon α |
EP3061461A1 (en) | 2004-10-29 | 2016-08-31 | ratiopharm GmbH | Remodeling and glycopegylation of fibroblast growth factor (fgf) |
MX2007007587A (es) | 2004-12-22 | 2007-12-11 | Ambrx Inc | Formulaciones de la hormona del crecimiento humano que comprenden un aminoacido codificado de manera no natural. |
WO2006073846A2 (en) | 2004-12-22 | 2006-07-13 | Ambrx, Inc. | Methods for expression and purification of recombinant human growth hormone |
CN101087875B (zh) | 2004-12-22 | 2012-08-22 | Ambrx公司 | 氨酰基-tRNA合成酶的组合物及其用途 |
BRPI0519430A2 (pt) | 2004-12-22 | 2009-02-10 | Ambrx Inc | hormânio do crescimento humano modificado |
WO2006074467A2 (en) | 2005-01-10 | 2006-07-13 | Neose Technologies, Inc. | Glycopegylated granulocyte colony stimulating factor |
RU2007132188A (ru) | 2005-01-25 | 2009-03-10 | Селл Терапьютикс, Инк. (Us) | Конъюгаты биологически активных белков, имеющие модифицированное время полужизни in vivo |
WO2006097682A1 (en) * | 2005-03-18 | 2006-09-21 | Ucl Business Plc | Mechano growth factor peptides and their use |
WO2006102659A2 (en) * | 2005-03-23 | 2006-09-28 | Nektar Therapeutics Al, Corporation | CONJUGATES OF AN hGH MOIETY AND A POLYMER |
JP2008534640A (ja) | 2005-04-05 | 2008-08-28 | イステイチユート・デイ・リチエルケ・デイ・ビオロジア・モレコラーレ・ピ・アンジエレツテイ・エツセ・ピー・アー | タンパク質の機能部位またはエピトープの遮蔽方法 |
EP1871795A4 (en) | 2005-04-08 | 2010-03-31 | Biogenerix Ag | COMPOSITIONS AND METHOD FOR PRODUCING GLYCOSYLATION MUTANTS OF A PROTEASE-RESISTANT HUMAN GROWTH HORMONE |
WO2006127910A2 (en) | 2005-05-25 | 2006-11-30 | Neose Technologies, Inc. | Glycopegylated erythropoietin formulations |
US20110003744A1 (en) * | 2005-05-25 | 2011-01-06 | Novo Nordisk A/S | Glycopegylated Erythropoietin Formulations |
EP1891231A4 (en) | 2005-05-25 | 2011-06-22 | Novo Nordisk As | GLYCOPEGYLATED FACTOR IX |
CA2609205A1 (en) | 2005-06-03 | 2006-12-14 | Ambrx, Inc. | Improved human interferon molecules and their uses |
US8028453B2 (en) * | 2005-06-16 | 2011-10-04 | Hold That Thought, Inc. | Apparatus and methods for displaying a card |
ES2553160T3 (es) | 2005-06-17 | 2015-12-04 | Novo Nordisk Health Care Ag | Reducción y derivatización selectivas de proteínas Factor VII transformadas por ingeniería que comprenden al menos una cisteína no nativa |
JP2008543943A (ja) * | 2005-06-20 | 2008-12-04 | ペプゲン コーポレイション | ヒトインターフェロンアルファ類似体とインターフェロンタウの低毒性長期循環性キメラ |
US7695710B2 (en) * | 2005-06-20 | 2010-04-13 | Pepgen Corporation | Antitumor and antiviral combination therapies using low-toxicity, long-circulating human interferon-alpha analogs |
WO2007002886A2 (en) * | 2005-06-29 | 2007-01-04 | The Research Foundation Of State University Of New York | Compositions and methods for less immunogenic pr0tein-lip1d complexes |
WO2007021822A2 (en) * | 2005-08-09 | 2007-02-22 | The Research Foundation Of State Of University Of New York At Buffalo | Compositions and methods of preparation of liposomal microparticulate il-12 |
US20070105755A1 (en) | 2005-10-26 | 2007-05-10 | Neose Technologies, Inc. | One pot desialylation and glycopegylation of therapeutic peptides |
WO2007026972A2 (en) * | 2005-09-01 | 2007-03-08 | Canon Kabushiki Kaisha | Binding protein molecule |
US8168592B2 (en) | 2005-10-21 | 2012-05-01 | Amgen Inc. | CGRP peptide antagonists and conjugates |
US20090048440A1 (en) | 2005-11-03 | 2009-02-19 | Neose Technologies, Inc. | Nucleotide Sugar Purification Using Membranes |
WO2007059312A2 (en) | 2005-11-16 | 2007-05-24 | Ambrx, Inc. | Methods and compositions comprising non-natural amino acids |
US7875288B2 (en) * | 2006-03-30 | 2011-01-25 | The Research Foundation Of State University Of New York | Method for treating blood coagulation disorders |
EP2007357B1 (en) * | 2006-03-30 | 2016-11-09 | The Research Foundation Of State University Of New York | Compositions of less immunogenic and long-circulating protein-lipid complexes |
US7645860B2 (en) * | 2006-03-31 | 2010-01-12 | Baxter Healthcare S.A. | Factor VIII polymer conjugates |
EP2010222A1 (en) | 2006-03-31 | 2009-01-07 | Baxter International Inc. | Pegylated factor viii |
US7985839B2 (en) * | 2006-03-31 | 2011-07-26 | Baxter International Inc. | Factor VIII polymer conjugates |
US7982010B2 (en) * | 2006-03-31 | 2011-07-19 | Baxter International Inc. | Factor VIII polymer conjugates |
EP2004231A4 (en) | 2006-04-07 | 2013-07-10 | Nektar Therapeutics | CONJUGATES OF ANTI-TNF-ALPHA ANTIBODY |
EP2444499A3 (en) | 2006-05-02 | 2012-05-09 | Allozyne, Inc. | Amino acid substituted molecules |
US20080096819A1 (en) * | 2006-05-02 | 2008-04-24 | Allozyne, Inc. | Amino acid substituted molecules |
EP2213733A3 (en) | 2006-05-24 | 2010-12-29 | Novo Nordisk Health Care AG | Factor IX analogues having prolonged in vivo half life |
CN101484471B (zh) | 2006-06-30 | 2013-11-06 | 诺沃-诺迪斯克有限公司 | 抗-nkg2a抗体及其用途 |
CN101516388B (zh) | 2006-07-21 | 2012-10-31 | 诺和诺德公司 | 通过o-联糖基化序列的肽的糖基化 |
EP2615108B1 (en) | 2006-09-08 | 2016-10-26 | Ambrx, Inc. | Modified human plasma polypeptide or fc scaffolds and thier uses |
CA2662753C (en) | 2006-09-08 | 2016-02-23 | Ambrx, Inc. | Hybrid suppressor trna for vertebrate cells |
JP2008069073A (ja) * | 2006-09-12 | 2008-03-27 | Yokohama Tlo Co Ltd | ラクトフェリン複合体及びその製造方法 |
AU2007296056B2 (en) * | 2006-09-15 | 2012-09-13 | Enzon Pharmaceuticals, Inc. | Targeted polymeric prodrugs containing multifunctional linkers |
US8367065B2 (en) * | 2006-09-15 | 2013-02-05 | Enzon Pharmaceuticals, Inc. | Targeted polymeric prodrugs containing multifunctional linkers |
US7985783B2 (en) | 2006-09-21 | 2011-07-26 | The Regents Of The University Of California | Aldehyde tags, uses thereof in site-specific protein modification |
EP2054521A4 (en) | 2006-10-03 | 2012-12-19 | Novo Nordisk As | METHODS OF PURIFYING CONJUGATES OF POLYPEPTIDES |
MX2009005466A (es) * | 2006-11-22 | 2009-08-17 | Adnexus A Bristol Myers Sqibb | Terapeuticos dirigidos a base de proteinas manipuladas para receptores de tirosina cinasas, incluyendo receptor de factor de crecimiento tipo insulina-i. |
WO2008074032A1 (en) | 2006-12-15 | 2008-06-19 | Baxter International Inc. | Factor viia- (poly) sialic acid conjugate having prolonged in vivo half-life |
CN103755789B (zh) * | 2007-01-30 | 2016-12-07 | 埃皮瓦克斯公司 | 调节性t细胞表位、组合物及其用途 |
ATE516814T1 (de) * | 2007-02-02 | 2011-08-15 | Bristol Myers Squibb Co | 10fn3 domain zur behandlung von krankheiten begleitet von unerwünschter angiogenese |
KR20160121601A (ko) | 2007-03-30 | 2016-10-19 | 암브룩스, 인코포레이티드 | 변형된 fgf-21 폴리펩티드 및 그 용도 |
CA2682897C (en) | 2007-04-03 | 2016-11-22 | Biogenerix Ag | Methods of treatment using glycopegylated g-csf |
EP2076533B1 (en) | 2007-05-02 | 2014-10-08 | Ambrx, Inc. | Modified interferon beta polypeptides and their uses |
WO2008154639A2 (en) | 2007-06-12 | 2008-12-18 | Neose Technologies, Inc. | Improved process for the production of nucleotide sugars |
US7968811B2 (en) * | 2007-06-29 | 2011-06-28 | Harley-Davidson Motor Company Group, Inc. | Integrated ignition and key switch |
US20090110679A1 (en) * | 2007-07-13 | 2009-04-30 | Luk-Chiu Li | Methods and compositions for pulmonary administration of a TNFa inhibitor |
CA2707840A1 (en) | 2007-08-20 | 2009-02-26 | Allozyne, Inc. | Amino acid substituted molecules |
CA3128656A1 (en) | 2007-08-22 | 2009-02-26 | The Regents Of The University Of California | Activatable binding polypeptides and methods of identification and use thereof |
US8207112B2 (en) | 2007-08-29 | 2012-06-26 | Biogenerix Ag | Liquid formulation of G-CSF conjugate |
US8877688B2 (en) | 2007-09-14 | 2014-11-04 | Adimab, Llc | Rationally designed, synthetic antibody libraries and uses therefor |
BRPI0816785A2 (pt) | 2007-09-14 | 2017-05-02 | Adimab Inc | bibliotecas de anticorpos sintéticos racionalmente desenhadas, e, usos para as mesmas |
AU2008322886A1 (en) * | 2007-11-15 | 2009-05-22 | Australasian Food Group Pty Ltd. | Production of food products with enhanced in mouth and mental refreshment |
US8946148B2 (en) | 2007-11-20 | 2015-02-03 | Ambrx, Inc. | Modified insulin polypeptides and their uses |
CN101946171B (zh) * | 2007-12-14 | 2014-03-12 | 拜奥蒂乌姆股份有限公司 | 荧光化合物 |
DK2222706T4 (en) | 2007-12-14 | 2016-11-21 | Novo Nordisk As | Antibodies that bind to NKG2D and its use |
RU2010133892A (ru) | 2008-01-24 | 2012-02-27 | Ново Нордиск А/С (DK) | Гуманизированные моноклональные антитела против человеческого nkg2a |
NZ586947A (en) | 2008-02-08 | 2012-11-30 | Ambrx Inc | Modified leptin polypeptides and their uses |
JP2011517314A (ja) * | 2008-02-14 | 2011-06-02 | ブリストル−マイヤーズ スクイブ カンパニー | Egfrに結合する操作されたタンパク質に基づく標的化された治療薬 |
MX2010009190A (es) | 2008-02-20 | 2010-09-10 | G2 Inflammation Pty Ltd | Anticuerpos anti-c5ar humanizados. |
CN101965200B (zh) | 2008-02-27 | 2013-06-19 | 诺沃-诺迪斯克有限公司 | 缀合的因子ⅷ分子 |
EP2799448A1 (en) | 2008-05-22 | 2014-11-05 | Bristol-Myers Squibb Company | Multivalent fibronectin based scaffold domain proteins |
US10138283B2 (en) | 2008-07-23 | 2018-11-27 | Ambrx, Inc. | Modified bovine G-CSF polypeptides and their uses |
NZ601659A (en) | 2008-09-26 | 2014-02-28 | Ambrx Inc | Modified animal erythropoietin polypeptides and their uses |
EA201170493A1 (ru) | 2008-09-26 | 2011-10-31 | Амбркс, Инк. | Микроорганизмы и вакцины, зависимые от репликации неприродных аминокислот |
KR20110112301A (ko) | 2008-11-18 | 2011-10-12 | 메리맥 파마슈티컬즈, 인크. | 인간 혈청 알부민 링커 및 그 콘쥬게이트 |
TWI496582B (zh) | 2008-11-24 | 2015-08-21 | 必治妥美雅史谷比公司 | 雙重專一性之egfr/igfir結合分子 |
CA2745317C (en) | 2008-12-22 | 2019-03-05 | Ida Hilden | Antibodies against tissue factor pathway inhibitor |
CA2749339A1 (en) | 2009-01-12 | 2010-07-15 | Cytomx Therapeutics, Llc | Modified antibody compositions, methods of making and using thereof |
US9181341B2 (en) | 2009-01-19 | 2015-11-10 | Innate Pharma | Anti-KIR3D antibodies |
CA2753294A1 (en) | 2009-02-23 | 2010-08-26 | Cytomx Therapeutics, Inc. | Proproteins and methods of use thereof |
US8067201B2 (en) * | 2009-04-17 | 2011-11-29 | Bristol-Myers Squibb Company | Methods for protein refolding |
WO2010150213A1 (en) * | 2009-06-25 | 2010-12-29 | Danisco A/S | Protein |
EP2448593B1 (en) | 2009-07-03 | 2020-11-25 | Bionor Immuno AS | Hiv related peptides combination or fusion for use in hiv vaccine composition or as diagnostic means |
AU2010277438B2 (en) | 2009-07-27 | 2015-08-20 | Baxalta GmbH | Glycopolysialylation of non-blood coagulation proteins |
EP3093029A1 (en) | 2009-07-27 | 2016-11-16 | Baxalta GmbH | Blood coagulation protein conjugates |
US8809501B2 (en) | 2009-07-27 | 2014-08-19 | Baxter International Inc. | Nucleophilic catalysts for oxime linkage |
US8642737B2 (en) | 2010-07-26 | 2014-02-04 | Baxter International Inc. | Nucleophilic catalysts for oxime linkage |
DK2459224T3 (en) * | 2009-07-27 | 2016-07-25 | Baxalta GmbH | Blodstørkningsproteinkonjugater |
EP2475682B1 (en) | 2009-09-10 | 2018-01-31 | UCB Biopharma SPRL | Multivalent antibodies |
US8658434B2 (en) * | 2009-10-28 | 2014-02-25 | Biotium, Inc. | Fluorescent pyrene compounds |
GB0920127D0 (en) * | 2009-11-17 | 2009-12-30 | Ucb Pharma Sa | Antibodies |
MX349301B (es) | 2009-12-21 | 2017-07-21 | Ambrx Inc | Polipéptidos de somatotropina bovina modificados y sus usos. |
WO2011087810A1 (en) | 2009-12-21 | 2011-07-21 | Ambrx, Inc. | Modified porcine somatotropin polypeptides and their uses |
TWI513466B (zh) | 2010-01-20 | 2015-12-21 | Boehringer Ingelheim Int | 抗凝血劑解毒劑 |
WO2011100508A2 (en) * | 2010-02-12 | 2011-08-18 | Arizona Board Of Regents For And On Behalf Of Arizona State University | Methods and compositions related to glycoprotein-immunoglobulin fusions |
RS61082B1 (sr) | 2010-02-26 | 2020-12-31 | Novo Nordisk As | Stabilno antitelo koje sadrži kompozicije |
JP6148013B2 (ja) | 2010-03-05 | 2017-06-14 | リグショスピタレト | 補体活性化のキメラ抑制分子 |
TW201138808A (en) | 2010-05-03 | 2011-11-16 | Bristol Myers Squibb Co | Serum albumin binding molecules |
EP2569331A1 (en) | 2010-05-10 | 2013-03-20 | Perseid Therapeutics LLC | Polypeptide inhibitors of vla4 |
ES2573108T3 (es) | 2010-05-26 | 2016-06-06 | Bristol-Myers Squibb Company | Proteínas de armazón a base de fibronectina que tienen estabilidad mejorada |
KR20130086144A (ko) | 2010-05-28 | 2013-07-31 | 노보 노르디스크 에이/에스 | 항체 및 보존제를 포함하는 안정한 다중-투여 조성물 |
US9127052B2 (en) | 2010-06-29 | 2015-09-08 | Centre National De La Recherche Scientifique | LLT-1 antibodies with new functional properties |
TW201212938A (en) | 2010-06-30 | 2012-04-01 | Novo Nordisk As | Antibodies that are capable of specifically binding tissue factor pathway inhibitor |
KR102159272B1 (ko) | 2010-07-16 | 2020-09-24 | 아디맵 엘엘씨 | 항체 라이브러리 |
US9567386B2 (en) | 2010-08-17 | 2017-02-14 | Ambrx, Inc. | Therapeutic uses of modified relaxin polypeptides |
RS65223B1 (sr) | 2010-08-17 | 2024-03-29 | Ambrx Inc | Modifikovani polipeptidi relaksina i njihova primena |
TWI480288B (zh) | 2010-09-23 | 2015-04-11 | Lilly Co Eli | 牛顆粒細胞群落刺激因子及其變體之調配物 |
CA2822591C (en) | 2010-12-22 | 2020-12-29 | Baxter International Inc. | Materials and methods for conjugating a water soluble fatty acid derivative to a protein |
KR20140009437A (ko) | 2011-03-30 | 2014-01-22 | 베링거 인겔하임 인터내셔날 게엠베하 | 항응고제 해독제 |
JP6038121B2 (ja) | 2011-04-21 | 2016-12-07 | ガーバン インスティテュート オブ メディカル リサーチ | 修飾された可変ドメイン分子及びその製造及び使用の方法b |
CN103702721A (zh) | 2011-05-31 | 2014-04-02 | 诺沃—诺迪斯克有限公司 | Il-21表位和il-21配体 |
CN103596982B (zh) | 2011-06-06 | 2016-11-02 | 诺沃—诺迪斯克有限公司 | 治疗性抗体 |
CA2838220C (en) | 2011-06-17 | 2020-07-21 | Novo Nordisk A/S | Use of nkg2a antibodies for treatment of bone loss |
KR20140054009A (ko) | 2011-07-01 | 2014-05-08 | 바이엘 인텔렉쳐 프로퍼티 게엠베하 | 릴랙신 융합 폴리펩타이드 및 그의 용도 |
CN103747807B (zh) | 2011-07-05 | 2016-12-07 | 比奥阿赛斯技术有限公司 | P97‑抗体缀合物和使用方法 |
WO2013011062A2 (en) | 2011-07-18 | 2013-01-24 | Novo Nordisk A/S | Oscar antagonists |
WO2013011063A1 (en) | 2011-07-18 | 2013-01-24 | Novo Nordisk A/S | Antagonistic antibodies against oscar |
WO2013011059A1 (en) | 2011-07-18 | 2013-01-24 | Novo Nordisk A/S | Antagonist antibodies against oscar |
WO2013011061A1 (en) | 2011-07-18 | 2013-01-24 | Novo Nordisk A/S | Antagonistic antibodies against oscar |
WO2013092983A2 (en) | 2011-12-23 | 2013-06-27 | Innate Pharma | Enzymatic conjugation of polypeptides |
HUE036955T2 (hu) | 2012-02-15 | 2018-08-28 | Novo Nordisk As | Antitestek, amelyek a trigger receptort kötik és blokkolják, amely Myeloid-sejteken-1 (TREM-1) van expresszálva |
US9550830B2 (en) | 2012-02-15 | 2017-01-24 | Novo Nordisk A/S | Antibodies that bind and block triggering receptor expressed on myeloid cells-1 (TREM-1) |
LT2814842T (lt) | 2012-02-15 | 2018-11-12 | Novo Nordisk A/S | Antikūnai, kurie suriša peptidoglikaną atpažįstantį baltymą 1 |
CN104717974A (zh) | 2012-06-06 | 2015-06-17 | 比奥诺尔免疫有限公司 | 疫苗 |
EP3505534A1 (en) | 2012-06-08 | 2019-07-03 | Sutro Biopharma, Inc. | Antibodies comprising sitespecific nonnatural amino acid residues, methods of their preparation and methods of their use |
US9732161B2 (en) | 2012-06-26 | 2017-08-15 | Sutro Biopharma, Inc. | Modified Fc proteins comprising site-specific non-natural amino acid residues, conjugates of the same, methods of their preparation and methods of their use |
WO2014006230A1 (en) | 2012-07-06 | 2014-01-09 | Novo Nordisk A/S | Il-20 epitopes and il-20 ligands |
WO2014009426A2 (en) | 2012-07-13 | 2014-01-16 | Innate Pharma | Screening of conjugated antibodies |
AU2013296557B2 (en) | 2012-07-31 | 2019-04-18 | Bioasis Technologies Inc. | Dephosphorylated lysosomal storage disease proteins and methods of use thereof |
WO2014036520A1 (en) | 2012-08-30 | 2014-03-06 | Merrimack Pharmaceuticals, Inc. | Combination therapies comprising anti-erbb3 agents |
PL3584255T3 (pl) | 2012-08-31 | 2022-05-16 | Sutro Biopharma, Inc. | Modyfikowane aminokwasy zawierające grupę azydkową |
US10036010B2 (en) | 2012-11-09 | 2018-07-31 | Innate Pharma | Recognition tags for TGase-mediated conjugation |
WO2014074218A1 (en) | 2012-11-12 | 2014-05-15 | Redwood Bioscience, Inc. | Compounds and methods for producing a conjugate |
WO2014078733A1 (en) | 2012-11-16 | 2014-05-22 | The Regents Of The University Of California | Pictet-spengler ligation for protein chemical modification |
US9310374B2 (en) | 2012-11-16 | 2016-04-12 | Redwood Bioscience, Inc. | Hydrazinyl-indole compounds and methods for producing a conjugate |
US10077315B2 (en) | 2013-02-05 | 2018-09-18 | Engmab Sàrl | Bispecific antibodies against CD3 and BCMA |
EP2762496A1 (en) | 2013-02-05 | 2014-08-06 | EngMab AG | Method for the selection of antibodies against BCMA |
EP2970433B1 (en) | 2013-03-13 | 2019-09-18 | Bioasis Technologies Inc. | Fragments of p97 and uses thereof |
US9896513B2 (en) | 2013-03-15 | 2018-02-20 | Novo Nordisk A/S | Antibodies capable of specifically binding two epitopes on tissue factor pathway inhibitor |
US10611824B2 (en) | 2013-03-15 | 2020-04-07 | Innate Pharma | Solid phase TGase-mediated conjugation of antibodies |
EP2789630A1 (en) | 2013-04-09 | 2014-10-15 | EngMab AG | Bispecific antibodies against CD3e and ROR1 |
WO2014202773A1 (en) | 2013-06-20 | 2014-12-24 | Innate Pharma | Enzymatic conjugation of polypeptides |
JP6744212B2 (ja) | 2013-06-21 | 2020-08-19 | イナート・ファルマ・ソシエテ・アノニムInnate Pharma Pharma S.A. | ポリペプチドの酵素的結合 |
US9764039B2 (en) | 2013-07-10 | 2017-09-19 | Sutro Biopharma, Inc. | Antibodies comprising multiple site-specific non-natural amino acid residues, methods of their preparation and methods of their use |
WO2015007337A1 (en) | 2013-07-19 | 2015-01-22 | Bionor Immuno As | Method for the vaccination against hiv |
WO2015031673A2 (en) | 2013-08-28 | 2015-03-05 | Bioasis Technologies Inc. | Cns-targeted conjugates having modified fc regions and methods of use thereof |
US9840493B2 (en) | 2013-10-11 | 2017-12-12 | Sutro Biopharma, Inc. | Modified amino acids comprising tetrazine functional groups, methods of preparation, and methods of their use |
EA201690780A1 (ru) | 2013-10-15 | 2016-08-31 | Сиэтл Дженетикс, Инк. | Пегилированные лекарственные средства-линкеры для улучшенной фармакокинетики конъюгатов лиганд-лекарственное средство |
US20160297892A1 (en) | 2013-11-07 | 2016-10-13 | Novo Nordisk A/S | Novel Methods and Antibodies for Treating Coagulapathy |
CN115504924A (zh) | 2013-11-27 | 2022-12-23 | 雷德伍德生物科技股份有限公司 | 肼基-吡咯并化合物及用于生成缀合物的方法 |
JOP20200094A1 (ar) | 2014-01-24 | 2017-06-16 | Dana Farber Cancer Inst Inc | جزيئات جسم مضاد لـ pd-1 واستخداماتها |
JOP20200096A1 (ar) | 2014-01-31 | 2017-06-16 | Children’S Medical Center Corp | جزيئات جسم مضاد لـ tim-3 واستخداماتها |
MX370138B (es) | 2014-02-26 | 2019-12-03 | Univ Texas | Liberación de protones de nitrobenzaldehído para la manipulación de la acidosis celular. |
LT3116909T (lt) | 2014-03-14 | 2020-02-10 | Novartis Ag | Antikūno molekulės prieš lag-3 ir jų panaudojimas |
EP3119423B1 (en) | 2014-03-15 | 2022-12-14 | Novartis AG | Treatment of cancer using chimeric antigen receptor |
SG11201607820QA (en) | 2014-03-20 | 2016-10-28 | Bristol Myers Squibb Co | Serum albumin-binding fibronectin type iii domains |
AU2015279316B2 (en) | 2014-06-27 | 2021-03-04 | Innate Pharma | Multispecific NKp46 binding proteins |
CA2952532A1 (en) | 2014-06-27 | 2015-12-30 | Innate Pharma | Multispecific antigen binding proteins |
EP3026061A1 (en) | 2014-11-26 | 2016-06-01 | Novo Nordisk A/S | Site directed mutagenesis of trem-1 antibodies for decreasing viscosity. |
KR20240029114A (ko) | 2014-07-17 | 2024-03-05 | 노보 노르디스크 에이/에스 | 점도를 감소시키기 위한 trem-1 항체의 부위 지정 돌연변이유발 |
EP2975056A1 (en) | 2014-07-17 | 2016-01-20 | Novo Nordisk A/S | Site directed mutagenesis of TREM-1 antibodies for decreasing viscosity |
WO2016014553A1 (en) | 2014-07-21 | 2016-01-28 | Novartis Ag | Sortase synthesized chimeric antigen receptors |
ES2805475T3 (es) | 2014-07-21 | 2021-02-12 | Novartis Ag | Tratamiento del cáncer utilizando un receptor antigénico quimérico de CD33 |
EP3193915A1 (en) | 2014-07-21 | 2017-07-26 | Novartis AG | Combinations of low, immune enhancing. doses of mtor inhibitors and cars |
EP3172237A2 (en) | 2014-07-21 | 2017-05-31 | Novartis AG | Treatment of cancer using humanized anti-bcma chimeric antigen receptor |
EP3660042B1 (en) | 2014-07-31 | 2023-01-11 | Novartis AG | Subset-optimized chimeric antigen receptor-containing t-cells |
AU2015301460B2 (en) | 2014-08-14 | 2021-04-08 | Novartis Ag | Treatment of cancer using GFR alpha-4 chimeric antigen receptor |
EP3712171A1 (en) | 2014-08-19 | 2020-09-23 | Novartis AG | Treatment of cancer using a cd123 chimeric antigen receptor |
MX2017003645A (es) | 2014-09-17 | 2017-05-30 | Novartis Ag | Direccion de celulas citotoxicas con receptores quimericos para inmunoterapia adoptiva. |
WO2016055592A1 (en) | 2014-10-09 | 2016-04-14 | Engmab Ag | Bispecific antibodies against cd3epsilon and ror1 |
PE20171067A1 (es) | 2014-10-14 | 2017-07-24 | Novartis Ag | Moleculas de anticuerpo que se unen a pd-l1 y usos de las mismas |
CA2965502A1 (en) | 2014-10-24 | 2016-04-28 | Bristol-Myers Squibb Company | Modified fgf-21 polypeptides and uses thereof |
WO2016090034A2 (en) | 2014-12-03 | 2016-06-09 | Novartis Ag | Methods for b cell preconditioning in car therapy |
WO2016102657A1 (en) | 2014-12-23 | 2016-06-30 | Novo Nordisk A/S | Alpha-cell re-generation combined with conversion to beta cells |
US10253086B2 (en) | 2015-04-08 | 2019-04-09 | Novartis Ag | CD20 therapies, CD22 therapies, and combination therapies with a CD19 chimeric antigen receptor (CAR)-expressing cell |
EP3286211A1 (en) | 2015-04-23 | 2018-02-28 | Novartis AG | Treatment of cancer using chimeric antigen receptor and protein kinase a blocker |
EP3313876A2 (en) | 2015-06-23 | 2018-05-02 | Innate Pharma | Multispecific antigen binding proteins |
WO2016207278A1 (en) | 2015-06-23 | 2016-12-29 | Innate Pharma | Multispecific nk engager proteins |
WO2017019897A1 (en) | 2015-07-29 | 2017-02-02 | Novartis Ag | Combination therapies comprising antibody molecules to tim-3 |
ES2878188T3 (es) | 2015-07-29 | 2021-11-18 | Novartis Ag | Terapias de combinación que comprenden moléculas de anticuerpos contra LAG-3 |
DK3331910T3 (da) | 2015-08-03 | 2020-03-16 | Engmab Sarl | Monoklonale antistoffer mod humant b-cellemodningsantigen (bcma) |
KR20180056701A (ko) | 2015-09-23 | 2018-05-29 | 브리스톨-마이어스 스큅 컴퍼니 | 패스트-오프 레이트 혈청 알부민 결합 피브로넥틴 유형 iii 도메인 |
TWI814699B (zh) | 2015-12-04 | 2023-09-11 | 美商思進公司 | 四級胺化妥布賴森(tubulysin)化合物之結合物 |
US11793880B2 (en) | 2015-12-04 | 2023-10-24 | Seagen Inc. | Conjugates of quaternized tubulysin compounds |
KR20180094977A (ko) | 2015-12-17 | 2018-08-24 | 노파르티스 아게 | c-Met 억제제와 PD-1에 대한 항체 분자의 조합물 및 그의 용도 |
MX2018007423A (es) | 2015-12-17 | 2018-11-09 | Novartis Ag | Moleculas de anticuerpo que se unen a pd-1 y usos de las mismas. |
MA55746A (fr) | 2016-01-21 | 2022-03-02 | Novartis Ag | Molécules multispécifiques ciblant cll-1 |
RU2018134771A (ru) | 2016-03-04 | 2020-04-06 | Новартис Аг | Клетки, экспрессирующие множество молекул химерных антигенных рецепторов (car), и их применение |
WO2017165683A1 (en) | 2016-03-23 | 2017-09-28 | Novartis Ag | Cell secreted minibodies and uses thereof |
WO2017165851A1 (en) | 2016-03-25 | 2017-09-28 | Seattle Genetics, Inc. | Process for the preparation of pegylated drug-linkers and intermediates thereof |
ES2944607T3 (es) | 2016-04-15 | 2023-06-22 | Novartis Ag | Composiciones y métodos para la expresión selectiva de receptores quiméricos para el antígeno |
DK3458478T3 (da) | 2016-05-18 | 2021-03-22 | Boehringer Ingelheim Int | Anti-pd-1- og anti-lag3-antistoffer til cancerbehandling |
EP3463449A1 (en) | 2016-05-27 | 2019-04-10 | ALK-Abelló A/S | Immunogenic proteins and fragments thereof from allergenic mites |
WO2017210617A2 (en) | 2016-06-02 | 2017-12-07 | Porter, David, L. | Therapeutic regimens for chimeric antigen receptor (car)- expressing cells |
US10501775B2 (en) | 2016-07-12 | 2019-12-10 | Kite Pharma, Inc. | Antigen binding molecules and methods of use thereof |
JP7219376B2 (ja) | 2016-07-15 | 2023-02-08 | ノバルティス アーゲー | キメラ抗原受容体をキナーゼ阻害薬と併用して使用したサイトカイン放出症候群の治療及び予防 |
KR20190034588A (ko) | 2016-07-28 | 2019-04-02 | 노파르티스 아게 | 키메라 항원 수용체 및 pd-1 억제제의 조합 요법 |
CN110267677A (zh) | 2016-08-01 | 2019-09-20 | 诺华股份有限公司 | 使用与原m2巨噬细胞分子抑制剂组合的嵌合抗原受体治疗癌症 |
EP3523331A1 (en) | 2016-10-07 | 2019-08-14 | Novartis AG | Chimeric antigen receptors for the treatment of cancer |
MX2019004621A (es) | 2016-11-02 | 2019-11-28 | Engmab Sarl | Anticuerpo biespecifico contra bcma y cd3 y un farmaco inmunologico para uso combinado en el tratamiento del mieloma multiple. |
US11135307B2 (en) | 2016-11-23 | 2021-10-05 | Mersana Therapeutics, Inc. | Peptide-containing linkers for antibody-drug conjugates |
US11129906B1 (en) | 2016-12-07 | 2021-09-28 | David Gordon Bermudes | Chimeric protein toxins for expression by therapeutic bacteria |
EP3360898A1 (en) | 2017-02-14 | 2018-08-15 | Boehringer Ingelheim International GmbH | Bispecific anti-tnf-related apoptosis-inducing ligand receptor 2 and anti-cadherin 17 binding molecules for the treatment of cancer |
EP3559032A1 (en) | 2016-12-23 | 2019-10-30 | Innate Pharma | Heterodimeric antigen binding proteins |
US11535662B2 (en) | 2017-01-26 | 2022-12-27 | Novartis Ag | CD28 compositions and methods for chimeric antigen receptor therapy |
TW201837051A (zh) | 2017-02-08 | 2018-10-16 | 美商必治妥美雅史谷比公司 | 包含藥物動力學增強劑之經修飾之鬆弛素(relaxin)多肽及其用途 |
EP3589647A1 (en) | 2017-02-28 | 2020-01-08 | Novartis AG | Shp inhibitor compositions and uses for chimeric antigen receptor therapy |
IL269398B1 (en) | 2017-03-24 | 2024-01-01 | Seagen Inc | A process for the preparation of glucuronide-drug binders and their intermediates |
EP3615068A1 (en) | 2017-04-28 | 2020-03-04 | Novartis AG | Bcma-targeting agent, and combination therapy with a gamma secretase inhibitor |
US20200055948A1 (en) | 2017-04-28 | 2020-02-20 | Novartis Ag | Cells expressing a bcma-targeting chimeric antigen receptor, and combination therapy with a gamma secretase inhibitor |
PE20200717A1 (es) | 2017-06-22 | 2020-07-21 | Novartis Ag | Moleculas de anticuerpo que se unen a cd73 y usos de las mismas |
CA3066747A1 (en) | 2017-06-27 | 2019-01-03 | Novartis Ag | Dosage regimens for anti-tim-3 antibodies and uses thereof |
TWI820031B (zh) | 2017-07-11 | 2023-11-01 | 美商坎伯斯治療有限責任公司 | 結合人類cd137之促效劑抗體及其用途 |
JP2020527572A (ja) | 2017-07-20 | 2020-09-10 | ノバルティス アーゲー | 抗lag−3抗体の投薬量レジメンおよびその使用 |
US11718679B2 (en) | 2017-10-31 | 2023-08-08 | Compass Therapeutics Llc | CD137 antibodies and PD-1 antagonists and uses thereof |
CA3081602A1 (en) | 2017-11-16 | 2019-05-23 | Novartis Ag | Combination therapies |
US11851497B2 (en) | 2017-11-20 | 2023-12-26 | Compass Therapeutics Llc | CD137 antibodies and tumor antigen-targeting antibodies and uses thereof |
US20200325232A1 (en) | 2017-11-21 | 2020-10-15 | Innate Pharma | Multispecific antigen binding proteins |
EP3732254A4 (en) | 2017-12-26 | 2021-12-22 | Becton, Dickinson and Company | DEEP UV-EXCITABLE WATER-SOLVATIZED POLYMER DYES |
EP3746116A1 (en) | 2018-01-31 | 2020-12-09 | Novartis AG | Combination therapy using a chimeric antigen receptor |
US10844228B2 (en) | 2018-03-30 | 2020-11-24 | Becton, Dickinson And Company | Water-soluble polymeric dyes having pendant chromophores |
PE20201343A1 (es) | 2018-04-02 | 2020-11-25 | Bristol Myers Squibb Co | Anticuerpos anti-trem-1 y usos de los mismos |
US20210147547A1 (en) | 2018-04-13 | 2021-05-20 | Novartis Ag | Dosage Regimens For Anti-Pd-L1 Antibodies And Uses Thereof |
EP3784351A1 (en) | 2018-04-27 | 2021-03-03 | Novartis AG | Car t cell therapies with enhanced efficacy |
EP3569618A1 (en) | 2018-05-19 | 2019-11-20 | Boehringer Ingelheim International GmbH | Antagonizing cd73 antibody |
CN112384534A (zh) | 2018-05-21 | 2021-02-19 | 指南针制药有限责任公司 | 用于增强nk细胞对靶细胞的杀死的组合物和方法 |
WO2019226658A1 (en) | 2018-05-21 | 2019-11-28 | Compass Therapeutics Llc | Multispecific antigen-binding compositions and methods of use |
WO2019227003A1 (en) | 2018-05-25 | 2019-11-28 | Novartis Ag | Combination therapy with chimeric antigen receptor (car) therapies |
WO2019232244A2 (en) | 2018-05-31 | 2019-12-05 | Novartis Ag | Antibody molecules to cd73 and uses thereof |
MX2020013443A (es) | 2018-06-13 | 2021-02-26 | Novartis Ag | Receptores de antigeno quimerico de bcma y usos de los mismos. |
US20210238268A1 (en) | 2018-06-19 | 2021-08-05 | Atarga, Llc | Antibody molecules to complement component 5 and uses thereof |
AR116109A1 (es) | 2018-07-10 | 2021-03-31 | Novartis Ag | Derivados de 3-(5-amino-1-oxoisoindolin-2-il)piperidina-2,6-diona y usos de los mismos |
WO2020023300A1 (en) | 2018-07-22 | 2020-01-30 | Bioasis Technologies, Inc. | Treatment of lymmphatic metastases |
WO2020021465A1 (en) | 2018-07-25 | 2020-01-30 | Advanced Accelerator Applications (Italy) S.R.L. | Method of treatment of neuroendocrine tumors |
JP7441826B2 (ja) | 2018-09-11 | 2024-03-01 | アンブルックス,インコーポレイテッド | インターロイキン-2ポリペプチド抱合物およびその使用 |
WO2020082057A1 (en) | 2018-10-19 | 2020-04-23 | Ambrx, Inc. | Interleukin-10 polypeptide conjugates, dimers thereof, and their uses |
GB201818477D0 (en) | 2018-11-13 | 2018-12-26 | Emstopa Ltd | Tissue plasminogen activator antibodies and method of use thereof |
CA3119161A1 (en) | 2018-11-13 | 2020-05-22 | Compass Therapeutics Llc | Multispecific binding constructs against checkpoint molecules and uses thereof |
EP3897637A1 (en) | 2018-12-20 | 2021-10-27 | Novartis AG | Dosing regimen and pharmaceutical combination comprising 3-(1-oxoisoindolin-2-yl)piperidine-2,6-dione derivatives |
JP2022513255A (ja) | 2018-12-20 | 2022-02-07 | ノバルティス アーゲー | HDM2-p53相互作用阻害剤とBCL2阻害剤との組み合わせ及び癌を処置するためのその使用 |
SG11202108254YA (en) | 2019-02-12 | 2021-08-30 | Ambrx Inc | Compositions containing, methods and uses of antibody-tlr agonist conjugates |
EA202192019A1 (ru) | 2019-02-15 | 2021-11-02 | Новартис Аг | Производные 3-(1-оксо-5-(пиперидин-4-ил)изоиндолин-2-ил)пиперидин-2,6-диона и пути их применения |
US10871640B2 (en) | 2019-02-15 | 2020-12-22 | Perkinelmer Cellular Technologies Germany Gmbh | Methods and systems for automated imaging of three-dimensional objects |
CN113329792A (zh) | 2019-02-15 | 2021-08-31 | 诺华股份有限公司 | 取代的3-(1-氧代异吲哚啉-2-基)哌啶-2,6-二酮衍生物及其用途 |
US20220088075A1 (en) | 2019-02-22 | 2022-03-24 | The Trustees Of The University Of Pennsylvania | Combination therapies of egfrviii chimeric antigen receptors and pd-1 inhibitors |
MA55519A (fr) | 2019-03-29 | 2022-02-09 | Atarga Llc | Anticorps anti-fgf23 |
US11208477B2 (en) | 2019-04-01 | 2021-12-28 | Novo Nordisk A/S | Antibodies and use thereof |
US20220332817A1 (en) | 2019-07-15 | 2022-10-20 | Bristol-Myers Squibb Company | Antibodies against human trem-1 and uses thereof |
JP2022540674A (ja) | 2019-07-15 | 2022-09-16 | ブリストル-マイヤーズ スクイブ カンパニー | 抗trem-1抗体およびその使用 |
KR20220077127A (ko) * | 2019-09-06 | 2022-06-08 | 더 리전츠 오브 더 유니버시티 오브 캘리포니아 | 암 치료를 위한 키메라 항원 수용체 및 관련 방법 및 조성물 |
JP2022553306A (ja) | 2019-10-21 | 2022-12-22 | ノバルティス アーゲー | Tim-3阻害剤およびその使用 |
BR112022007376A2 (pt) | 2019-10-21 | 2022-07-05 | Novartis Ag | Terapias de combinação com venetoclax e inibidores de tim-3 |
EP4065158A2 (en) | 2019-11-26 | 2022-10-05 | Novartis AG | Chimeric antigen receptors binding bcma and cd19 and uses thereof |
BR112022011902A2 (pt) | 2019-12-20 | 2022-09-06 | Novartis Ag | Terapias de combinação |
CN113186185B (zh) * | 2020-01-14 | 2023-05-26 | 东北林业大学 | 一种从哺乳动物粪便中高效富集宿主dna的方法 |
CA3167413A1 (en) | 2020-01-17 | 2021-07-22 | Novartis Ag | Combination comprising a tim-3 inhibitor and a hypomethylating agent for use in treating myelodysplastic syndrome or chronic myelomonocytic leukemia |
CN115298322A (zh) | 2020-01-17 | 2022-11-04 | 贝克顿迪金森公司 | 用于单细胞分泌组学的方法和组合物 |
CN115397460A (zh) | 2020-02-27 | 2022-11-25 | 诺华股份有限公司 | 制备表达嵌合抗原受体的细胞的方法 |
KR20220151202A (ko) | 2020-03-11 | 2022-11-14 | 암브룩스, 인코포레이티드 | 인터류킨-2 폴리펩타이드 접합체 및 그의 사용 방법 |
US20210355468A1 (en) | 2020-05-18 | 2021-11-18 | Bioasis Technologies, Inc. | Compositions and methods for treating lewy body dementia |
JP2023504675A (ja) | 2020-05-19 | 2023-02-06 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | ガンの処置のための結合分子 |
US20210371503A1 (en) | 2020-05-29 | 2021-12-02 | University Of Cologne | Neutralizing antibodies against sars-related coronavirus |
US20210393787A1 (en) | 2020-06-17 | 2021-12-23 | Bioasis Technologies, Inc. | Compositions and methods for treating frontotemporal dementia |
MX2022015852A (es) | 2020-06-23 | 2023-01-24 | Novartis Ag | Regimen de dosificacion que comprende derivados de 3-(1-oxoisoindolin-2-il)piperidina-2,6-diona. |
EP4182025A1 (en) | 2020-07-16 | 2023-05-24 | Novartis AG | Anti-betacellulin antibodies, fragments thereof, and multi-specific binding molecules |
WO2022026592A2 (en) | 2020-07-28 | 2022-02-03 | Celltas Bio, Inc. | Antibody molecules to coronavirus and uses thereof |
EP4188549A1 (en) | 2020-08-03 | 2023-06-07 | Novartis AG | Heteroaryl substituted 3-(1-oxoisoindolin-2-yl)piperidine-2,6-dione derivatives and uses thereof |
US20230296611A1 (en) | 2020-08-10 | 2023-09-21 | Innate Pharma | Cell surface mica and micb detection using antibodies |
TW202227449A (zh) | 2020-08-20 | 2022-07-16 | 美商Ambrx 公司 | 抗體-tlr促效劑偶聯物、其方法及用途 |
EP4204021A1 (en) | 2020-08-31 | 2023-07-05 | Advanced Accelerator Applications International S.A. | Method of treating psma-expressing cancers |
EP4204020A1 (en) | 2020-08-31 | 2023-07-05 | Advanced Accelerator Applications International S.A. | Method of treating psma-expressing cancers |
TW202233668A (zh) | 2020-10-21 | 2022-09-01 | 德商百靈佳殷格翰國際股份有限公司 | 用於治療眼部疾病之雙特異性抗-VEGF及抗-TrkB結合分子 |
JP2023548034A (ja) | 2020-10-22 | 2023-11-15 | ヤンセン バイオテツク,インコーポレーテツド | デルタ様リガンド3(dll3)抗原結合ドメインを含むタンパク質及びその使用 |
EP4240765A2 (en) | 2020-11-06 | 2023-09-13 | Novartis AG | Antibody fc variants |
CA3198447A1 (en) | 2020-11-13 | 2022-05-19 | Novartis Ag | Combination therapies with chimeric antigen receptor (car)-expressing cells |
WO2022162569A1 (en) | 2021-01-29 | 2022-08-04 | Novartis Ag | Dosage regimes for anti-cd73 and anti-entpd2 antibodies and uses thereof |
WO2022182872A2 (en) | 2021-02-24 | 2022-09-01 | Alladapt Immunotherapeutics, Inc. | Compositions and methods for identification of cross-reactive allergenic proteins and treatment of allergies |
CA3207652A1 (en) | 2021-03-26 | 2022-09-29 | Stephanie Cornen | Cytokine anchors for nkp46-binding nk cell engager proteins |
TW202304990A (zh) | 2021-03-26 | 2023-02-01 | 美商健生生物科技公司 | 針對成對螺旋絲tau之人源化抗體及其用途 |
KR20240004342A (ko) | 2021-04-03 | 2024-01-11 | 암브룩스, 인코포레이티드 | 항-her2 항체-약물 접합체 및 이의 용도 |
KR20230165913A (ko) | 2021-04-05 | 2023-12-05 | 이나뜨 파르마 에스.에이. | 면역조직화학 방법 및 kir3dl2-특이적 시약 |
TW202304979A (zh) | 2021-04-07 | 2023-02-01 | 瑞士商諾華公司 | 抗TGFβ抗體及其他治療劑用於治療增殖性疾病之用途 |
AR125874A1 (es) | 2021-05-18 | 2023-08-23 | Novartis Ag | Terapias de combinación |
EP4095156A1 (en) | 2021-05-28 | 2022-11-30 | Universität zu Köln | Neutralizing antibodies against hepatitis c virus |
EP4352098A1 (en) | 2021-06-09 | 2024-04-17 | Innate Pharma | Multispecific proteins binding to nkp46, a cytokine receptor, a tumour antigen and cd16a |
IL308531A (en) | 2021-06-09 | 2024-01-01 | Innate Pharma | Multiple specific antibodies that bind to CD20, NKP46, CD16 and are equipped with IL-2 |
WO2022258678A1 (en) | 2021-06-09 | 2022-12-15 | Innate Pharma | Multispecific proteins binding to nkp30, a cytokine receptor, a tumour antigen and cd16a |
WO2022258691A1 (en) | 2021-06-09 | 2022-12-15 | Innate Pharma | Multispecific proteins binding to nkg2d, a cytokine receptor, a tumour antigen and cd16a |
EP4355778A1 (en) | 2021-06-17 | 2024-04-24 | Boehringer Ingelheim International GmbH | Novel tri-specific binding molecules |
WO2023044483A2 (en) | 2021-09-20 | 2023-03-23 | Voyager Therapeutics, Inc. | Compositions and methods for the treatment of her2 positive cancer |
EP4155349A1 (en) | 2021-09-24 | 2023-03-29 | Becton, Dickinson and Company | Water-soluble yellow green absorbing dyes |
WO2023092004A1 (en) | 2021-11-17 | 2023-05-25 | Voyager Therapeutics, Inc. | Compositions and methods for the treatment of tau-related disorders |
EP4190810A1 (en) | 2021-12-01 | 2023-06-07 | Universität zu Köln | Neutralizing antibodies against sars-related coronavirus |
WO2023099688A1 (en) | 2021-12-01 | 2023-06-08 | Universität Zu Köln | Neutralizing antibodies against sars-related coronavirus |
TW202342548A (zh) | 2022-02-07 | 2023-11-01 | 美商威特拉公司 | 抗獨特型(anti-idiotype)抗體分子及其用途 |
WO2023170295A1 (en) | 2022-03-11 | 2023-09-14 | Janssen Pharmaceutica Nv | Multispecific antibodies and uses thereof |
WO2023170290A1 (en) | 2022-03-11 | 2023-09-14 | Janssen Pharmaceutica Nv | Multispecific antibodies and uses thereof |
TW202400636A (zh) | 2022-03-11 | 2024-01-01 | 比利時商健生藥品公司 | 多特異性抗體及其用途(一) |
WO2023220695A2 (en) | 2022-05-13 | 2023-11-16 | Voyager Therapeutics, Inc. | Compositions and methods for the treatment of her2 positive cancer |
WO2024007016A2 (en) | 2022-07-01 | 2024-01-04 | Beckman Coulter, Inc. | Novel fluorescent dyes and polymers from dihydrophenanthrene derivatives |
US20240052065A1 (en) | 2022-07-15 | 2024-02-15 | Boehringer Ingelheim International Gmbh | Binding molecules for the treatment of cancer |
WO2024030976A2 (en) | 2022-08-03 | 2024-02-08 | Voyager Therapeutics, Inc. | Compositions and methods for crossing the blood brain barrier |
WO2024044327A1 (en) | 2022-08-26 | 2024-02-29 | Beckman Coulter, Inc. | Dhnt monomers and polymer dyes with modified photophysical properties |
WO2024056861A1 (en) | 2022-09-15 | 2024-03-21 | Avidicure Ip B.V. | Multispecific antigen binding proteins for stimulating nk cells and use thereof |
Family Cites Families (58)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4179337A (en) | 1973-07-20 | 1979-12-18 | Davis Frank F | Non-immunogenic polypeptides |
US5049504A (en) * | 1986-11-24 | 1991-09-17 | Genex Corporation | Bioadhesive coding sequences |
US5202236A (en) * | 1984-09-13 | 1993-04-13 | Enzon Labs Inc. | Method of producing bioadhesive protein |
US5202256A (en) * | 1984-09-13 | 1993-04-13 | Enzon Labs, Inc. | Bioadhesive precursor protein expression vectors |
US4946778A (en) * | 1987-09-21 | 1990-08-07 | Genex Corporation | Single polypeptide chain binding molecules |
US4881175A (en) * | 1986-09-02 | 1989-11-14 | Genex Corporation | Computer based system and method for determining and displaying possible chemical structures for converting double- or multiple-chain polypeptides to single-chain polypeptides |
US5869620A (en) | 1986-09-02 | 1999-02-09 | Enzon, Inc. | Multivalent antigen-binding proteins |
US4704692A (en) * | 1986-09-02 | 1987-11-03 | Ladner Robert C | Computer based system and method for determining and displaying possible chemical structures for converting double- or multiple-chain polypeptides to single-chain polypeptides |
US5260203A (en) * | 1986-09-02 | 1993-11-09 | Enzon, Inc. | Single polypeptide chain binding molecules |
US5166320A (en) * | 1987-04-22 | 1992-11-24 | University Of Connecticut | Carrier system and method for the introduction of genes into mammalian cells |
US5258498A (en) | 1987-05-21 | 1993-11-02 | Creative Biomolecules, Inc. | Polypeptide linkers for production of biosynthetic proteins |
US5091513A (en) * | 1987-05-21 | 1992-02-25 | Creative Biomolecules, Inc. | Biosynthetic antibody binding sites |
US4904582A (en) * | 1987-06-11 | 1990-02-27 | Synthetic Genetics | Novel amphiphilic nucleic acid conjugates |
US5122614A (en) * | 1989-04-19 | 1992-06-16 | Enzon, Inc. | Active carbonates of polyalkylene oxides for modification of polypeptides |
US5358932A (en) * | 1989-12-29 | 1994-10-25 | Zymogenetics, Inc. | Hybrid protein C |
GB9012995D0 (en) * | 1990-06-11 | 1990-08-01 | Celltech Ltd | Multivalent antigen-binding proteins |
US5766897A (en) * | 1990-06-21 | 1998-06-16 | Incyte Pharmaceuticals, Inc. | Cysteine-pegylated proteins |
WO1992016555A1 (en) | 1991-03-18 | 1992-10-01 | Enzon, Inc. | Hydrazine containing conjugates of polypeptides and glycopolypeptides with polymers |
US5212075A (en) | 1991-04-15 | 1993-05-18 | The Regents Of The University Of California | Compositions and methods for introducing effectors to pathogens and cells |
US5872222A (en) | 1991-04-19 | 1999-02-16 | Tanox Biosystems, Inc. | Conjugates of polymers and antibodies specific for T lymphocytes, and their use as adjuvants |
US6787153B1 (en) * | 1991-06-28 | 2004-09-07 | Mitsubishi Chemical Corporation | Human monoclonal antibody specifically binding to surface antigen of cancer cell membrane |
US5521291A (en) | 1991-09-30 | 1996-05-28 | Boehringer Ingelheim International, Gmbh | Conjugates for introducing nucleic acid into higher eucaryotic cells |
US5981273A (en) * | 1991-09-30 | 1999-11-09 | Boehringer Ingelheim Int'l. Gmbh | Composition comprising an endosomolytic agent for introducing nucleic acid complexes into higher eucaryotic cells |
NZ244306A (en) * | 1991-09-30 | 1995-07-26 | Boehringer Ingelheim Int | Composition for introducing nucleic acid complexes into eucaryotic cells, complex containing nucleic acid and endosomolytic agent, peptide with endosomolytic domain and nucleic acid binding domain and preparation |
AU3178993A (en) | 1991-11-25 | 1993-06-28 | Enzon, Inc. | Multivalent antigen-binding proteins |
US6025165A (en) * | 1991-11-25 | 2000-02-15 | Enzon, Inc. | Methods for producing multivalent antigen-binding proteins |
ATE419355T1 (de) | 1992-02-06 | 2009-01-15 | Novartis Vaccines & Diagnostic | Marker für krebs und biosynthetisches bindeprotein dafür |
US5714350A (en) | 1992-03-09 | 1998-02-03 | Protein Design Labs, Inc. | Increasing antibody affinity by altering glycosylation in the immunoglobulin variable region |
US6113946A (en) | 1992-04-03 | 2000-09-05 | The Regents Of The University Of California | Self-assembling polynucleotide delivery system comprising dendrimer polycations |
US6329507B1 (en) | 1992-08-21 | 2001-12-11 | The Dow Chemical Company | Dimer and multimer forms of single chain polypeptides |
AU5670194A (en) | 1992-11-20 | 1994-06-22 | Enzon, Inc. | Linker for linked fusion polypeptides |
US5359030A (en) * | 1993-05-10 | 1994-10-25 | Protein Delivery, Inc. | Conjugation-stabilized polypeptide compositions, therapeutic delivery and diagnostic formulations comprising same, and method of making and using the same |
AU8052194A (en) | 1993-10-20 | 1995-05-08 | Enzon, Inc. | 2'- and/or 7- substituted taxoids |
US5880131A (en) | 1993-10-20 | 1999-03-09 | Enzon, Inc. | High molecular weight polymer-based prodrugs |
US5443953A (en) * | 1993-12-08 | 1995-08-22 | Immunomedics, Inc. | Preparation and use of immunoconjugates |
US5844107A (en) * | 1994-03-23 | 1998-12-01 | Case Western Reserve University | Compacted nucleic acids and their delivery to cells |
US5656465A (en) * | 1994-05-04 | 1997-08-12 | Therion Biologics Corporation | Methods of in vivo gene delivery |
US5730990A (en) * | 1994-06-24 | 1998-03-24 | Enzon, Inc. | Non-antigenic amine derived polymers and polymer conjugates |
US5888773A (en) | 1994-08-17 | 1999-03-30 | The United States Of America As Represented By The Department Of Health And Human Services | Method of producing single-chain Fv molecules |
US5670132A (en) | 1994-09-20 | 1997-09-23 | Immunomedics, Inc. | Modified radioantibody fragments for reduced renal uptake |
US5763733A (en) | 1994-10-13 | 1998-06-09 | Enzon, Inc. | Antigen-binding fusion proteins |
ATE202145T1 (de) | 1994-11-01 | 2001-06-15 | Winfried Wels | Nukleinsäure-einbringungssystem |
AU6255096A (en) | 1995-06-07 | 1996-12-30 | Mount Sinai School Of Medicine Of The City University Of New York, The | Pegylated modified proteins |
US5853723A (en) | 1995-09-21 | 1998-12-29 | University Of Utah Research Foundation | Targeting of peg antibody conjugates to islet cells |
BR9606706A (pt) | 1995-10-16 | 1999-04-06 | Unilever Nv | Análogo de fragmento de anticorpo biespecífico ou bivalente uso processo para produzir o mesmo |
US6090382A (en) * | 1996-02-09 | 2000-07-18 | Basf Aktiengesellschaft | Human antibodies that bind human TNFα |
CZ292465B6 (cs) * | 1996-02-09 | 2003-09-17 | Abbott Laboratories (Bermuda) Ltd. | Lidské protilátky k lidskému TNFalfa |
GB9625640D0 (en) | 1996-12-10 | 1997-01-29 | Celltech Therapeutics Ltd | Biological products |
US6025158A (en) | 1997-02-21 | 2000-02-15 | Genentech, Inc. | Nucleic acids encoding humanized anti-IL-8 monoclonal antibodies |
DK0968291T3 (da) | 1997-02-21 | 2004-06-07 | Genentech Inc | Antistoffragment-polymerkonjugater |
US6117980A (en) * | 1997-02-21 | 2000-09-12 | Genentech, Inc. | Humanized anti-IL-8 monoclonal antibodies |
US5830698A (en) * | 1997-03-14 | 1998-11-03 | Idec Pharmaceuticals Corporation | Method for integrating genes at specific sites in mammalian cells via homologous recombination and vectors for accomplishing the same |
CA2288994C (en) * | 1997-04-30 | 2011-07-05 | Enzon, Inc. | Polyalkylene oxide-modified single chain polypeptides |
GB9812545D0 (en) | 1998-06-10 | 1998-08-05 | Celltech Therapeutics Ltd | Biological products |
US6333396B1 (en) * | 1998-10-20 | 2001-12-25 | Enzon, Inc. | Method for targeted delivery of nucleic acids |
US6908963B2 (en) * | 2001-10-09 | 2005-06-21 | Nektar Therapeutics Al, Corporation | Thioester polymer derivatives and method of modifying the N-terminus of a polypeptide therewith |
PL369739A1 (en) * | 2001-11-12 | 2005-05-02 | Merck Patent Gmbh | Modified anti-tnf alpha antibody |
US7101978B2 (en) * | 2003-01-08 | 2006-09-05 | Applied Molecular Evolution | TNF-α binding molecules |
-
1998
- 1998-04-30 CA CA2288994A patent/CA2288994C/en not_active Expired - Lifetime
- 1998-04-30 AU AU72666/98A patent/AU7266698A/en not_active Abandoned
- 1998-04-30 JP JP54735198A patent/JP4187277B2/ja not_active Expired - Lifetime
- 1998-04-30 EP EP98920001A patent/EP0979102A4/en not_active Withdrawn
- 1998-04-30 WO PCT/US1998/008654 patent/WO1998048837A1/en active Application Filing
- 1998-04-30 EP EP98920006A patent/EP0981548A4/en not_active Withdrawn
- 1998-04-30 US US09/069,821 patent/US6323322B1/en not_active Expired - Lifetime
- 1998-04-30 JP JP54734798A patent/JP2002505574A/ja active Pending
- 1998-04-30 AU AU72668/98A patent/AU7266898A/en not_active Abandoned
- 1998-04-30 WO PCT/US1998/008662 patent/WO1998049198A1/en active Application Filing
- 1998-04-30 CA CA2288992A patent/CA2288992C/en not_active Expired - Lifetime
-
2001
- 2001-02-26 US US09/791,578 patent/US6872393B2/en not_active Expired - Lifetime
- 2001-02-26 US US09/791,540 patent/US6824782B2/en not_active Expired - Lifetime
- 2001-09-20 US US09/956,086 patent/US6743896B2/en not_active Expired - Lifetime
- 2001-09-20 US US09/956,087 patent/US6743908B2/en not_active Expired - Lifetime
-
2004
- 2004-04-23 US US10/831,063 patent/US20050042680A1/en not_active Abandoned
- 2004-08-02 US US10/909,948 patent/US7632504B2/en not_active Expired - Fee Related
- 2004-08-10 US US10/915,069 patent/US7150872B2/en not_active Expired - Fee Related
-
2008
- 2008-01-17 JP JP2008008563A patent/JP2008115193A/ja not_active Withdrawn
-
2009
- 2009-12-10 JP JP2009281051A patent/JP2010051331A/ja not_active Withdrawn
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2007516195A (ja) * | 2003-06-30 | 2007-06-21 | ドマンティス リミテッド | ポリペプチド |
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CA2288994A1 (en) | 1998-11-05 |
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EP0981548A1 (en) | 2000-03-01 |
CA2288992A1 (en) | 1998-11-05 |
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EP0981548A4 (en) | 2005-11-23 |
JP4187277B2 (ja) | 2008-11-26 |
WO1998048837A9 (en) | 1999-04-22 |
WO1998048837A1 (en) | 1998-11-05 |
EP0979102A1 (en) | 2000-02-16 |
US20020061307A1 (en) | 2002-05-23 |
JP2010051331A (ja) | 2010-03-11 |
US7150872B2 (en) | 2006-12-19 |
US6323322B1 (en) | 2001-11-27 |
US20050042680A1 (en) | 2005-02-24 |
CA2288994C (en) | 2011-07-05 |
US6824782B2 (en) | 2004-11-30 |
AU7266898A (en) | 1998-11-24 |
US20050048064A1 (en) | 2005-03-03 |
US7632504B2 (en) | 2009-12-15 |
US6872393B2 (en) | 2005-03-29 |
EP0979102A4 (en) | 2005-11-23 |
JP2002516610A (ja) | 2002-06-04 |
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