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1. 发明授权

US06440417B1 Antibodies to argatroban derivatives and their use in therapeutic and diagnostic treatments 失效
标题翻译：阿胺曲潘衍生物的抗体及其在治疗和诊断治疗中的应用
公开(公告)号：US06440417B1
公开(公告)日：2002-08-27
申请号：US09434605
申请日：1999-11-05
申请人： Karen Thibaudeau , Dominique Blanchard , Dominique P. Bridon , Alan M. Ezrin , Margaret Hardy , Nissab Boudjellab
发明人： Karen Thibaudeau , Dominique Blanchard , Dominique P. Bridon , Alan M. Ezrin , Margaret Hardy , Nissab Boudjellab
IPC分类号： C07K1644
CPC分类号： C07K16/44 , A61K2039/505
摘要： Antibodies to a therapeutic agent and its derivatives and conjugates are disclosed, including antibodies to argatroban and its derivatives and conjugates. The antibodies are useful as reagents in assays and diagnostic kits for determining the concentration of a therapeutic agent or its derivatives and conjugates in biological samples, and further have therapeutic uses in treatment for potential toxicity associated with stable therapeutic conjugates and derivatives, both in vivo and ex vivo.
摘要翻译：公开了治疗剂及其衍生物和缀合物的抗体，包括阿加曲班及其衍生物和缀合物的抗体。该抗体可用作用于测定和诊断试剂盒中的试剂，用于确定生物样品中治疗剂或其衍生物和缀合物的浓度，并且还具有用于治疗与稳定的治疗性缀合物和衍生物相关的潜在毒性的治疗用途，包括体内和离体

2. 发明授权

US06887470B1 Protection of endogenous therapeutic peptides from peptidase activity through conjugation to blood components 失效
标题翻译：通过与血液成分缀合，保护内源性治疗肽免受肽酶活性的影响
公开(公告)号：US06887470B1
公开(公告)日：2005-05-03
申请号：US09657276
申请日：2000-09-07
申请人： Dominique P. Bridon , Alan M. Ezrin , Peter G. Milner , Darren L. Holmes , Karen Thibaudeau
发明人： Dominique P. Bridon , Alan M. Ezrin , Peter G. Milner , Darren L. Holmes , Karen Thibaudeau
IPC分类号： A61K38/54 , A61K39/395 , C07K14/47 , C07K16/18 , C07K16/28 , C07K19/00
CPC分类号： C07K19/00
摘要： A method for protecting a peptide from peptidase activity in vivo, the peptide being composed of between 2 and 50 amino acids and having a C-terminus and an N-terminus and a C-terminus amino acid and an N-terminus amino acid is described. In the first step of the method, the peptide is modified by attaching a reactive group to the C-terminus amino acid, to the N-terminus amino acid, or to an amino acid located between the N-terminus and the C-terminus, such that the modified peptide is capable of forming a covalent bond in vivo with a reactive functionality on a blood component. In the next step, a covalent bond is formed between the reactive group and a reactive functionality on a blood component to form a peptide-blood component conjugate, thereby protecting said peptide from peptidase activity. The final step of the method involves the analyzing of the stability of the peptide-blood component conjugate to assess the protection of the peptide from peptidase activity.
摘要翻译：描述了一种在体内保护肽免受肽酶活性的方法，所述肽由2-50个氨基酸组成且具有C末端和N末端以及C末端氨基酸和N-末端氨基酸。在该方法的第一步中，通过将反应性基团连接到C末端氨基酸，N末端氨基酸或位于N末端和C末端之间的氨基酸来修饰肽，使得修饰的肽能够在体内与血液成分上的反应性官能团形成共价键。在下一步骤中，在反应性基团和血液成分上的反应性官能团之间形成共价键以形成肽 - 血液成分缀合物，从而保护所述肽免受肽酶活性。该方法的最后步骤包括分析肽 - 血液成分缀合物的稳定性，以评估肽对肽酶活性的保护。

3. 发明授权

US07256253B2 Protection of endogenous therapeutic peptides from peptidase activity through conjugation to blood components 失效
标题翻译：通过与血液成分缀合，保护内源性治疗肽免受肽酶活性的影响
公开(公告)号：US07256253B2
公开(公告)日：2007-08-14
申请号：US11066697
申请日：2005-02-25
申请人： Dominique P. Bridon , Alan M. Ezrin , Peter G. Milner , Darren L. Holmes , Karen Thibaudeau
发明人： Dominique P. Bridon , Alan M. Ezrin , Peter G. Milner , Darren L. Holmes , Karen Thibaudeau
IPC分类号： A61K38/00 , C07K14/00
CPC分类号： C07K19/00
摘要： A secretin or secretin derivative protected against peptidase activity. The secretin or derivative comprises a peptidic sequence and a reactive group selected from the group consisting of succinimidyl and maleimido groups capable of reacting with an amino group, hydroxyl group or thiol group on a blood component to form a stable covalent bond. The reactive group is attached at a position along the peptidic sequence that provides, when conjugated to a blood component, a higher stability against peptidase degradation than the unconjugated secretin or derivative, and therefore an increased maintenance of the therapeutic activity compared to the unconjugated secretin or derivative. Such a compound is thus effective to provide a source of secretin having a high stability against peptidases. A method for synthesizing such a compound is also described.
摘要翻译：保护蛋白酶活性的促胰液素或促胰液素衍生物。分泌素或衍生物包含肽类序列和选自能够与血液成分上的氨基，羟基或硫醇基反应形成稳定的共价键的琥珀酰亚胺基和马来酰亚胺基的反应性基团。反应性基团连接在沿着肽序列的位置，当与血液成分缀合时，其比非共轭分泌素或衍生物具有比肽酶降解更高的稳定性，因此与未缀合的促胰液素相比，治疗活性的维持得到增加衍生物。因此，这样的化合物有效地提供对肽酶具有高稳定性的促胰液素来源。还描述了合成这种化合物的方法。

4. 发明申请

US20090175821A1 Modified therapeutic peptides with extended half-lives in vivo 审中-公开
标题翻译：体内延长半衰期的修饰治疗肽
公开(公告)号：US20090175821A1
公开(公告)日：2009-07-09
申请号：US11982033
申请日：2007-10-31
申请人： Dominique P. Bridon , Alan M. Ezrin , Peter G. Milner , Darren L. Holmes , Karen Thibaudeau
发明人： Dominique P. Bridon , Alan M. Ezrin , Peter G. Milner , Darren L. Holmes , Karen Thibaudeau
IPC分类号： A61K38/38 , C07K19/00 , A61K38/21 , A61K38/28 , A61K38/22 , A61K38/18
CPC分类号： C07K14/57563 , A61K38/38 , A61K47/62 , A61K47/643
摘要： A method for protecting a peptide from peptidase activity in vivo, the peptide being composed of between 2 and 50 amino acids and having a C-terminus and an N-terminus and a C-terminus amino acid and an N-terminus amino acid is described. In the first step of the method, the peptide is modified by attaching a reactive group to the C-terminus amino acid, to the N-terminus amino acid, or to an amino acid located between the N-terminus and the C-terminus, such that the modified peptide is capable of forming a covalent bond in vivo with a reactive functionality on a blood component. In the next step, a covalent bond is formed between the reactive group and a reactive functionality on a blood component to form a peptide-blood component conjugate, thereby protecting said peptide from peptidase activity. The final step of the method involves the analyzing of the stability of the peptide-blood component conjugate to assess the protection of the peptide from peptidase activity.
摘要翻译：描述了一种在体内保护肽免受肽酶活性的方法，所述肽由2-50个氨基酸组成且具有C末端和N末端以及C末端氨基酸和N-末端氨基酸。在该方法的第一步中，通过将反应性基团连接到C末端氨基酸，N末端氨基酸或位于N末端和C末端之间的氨基酸来修饰肽，使得修饰的肽能够在体内与血液成分上的反应性官能团形成共价键。在下一步骤中，在反应性基团和血液成分上的反应性官能团之间形成共价键以形成肽 - 血液成分缀合物，从而保护所述肽免受肽酶活性。该方法的最后步骤包括分析肽 - 血液成分缀合物的稳定性，以评估肽对肽酶活性的保护。

5. 发明授权

US06849714B1 Protection of endogenous therapeutic peptides from peptidase activity through conjugation to blood components 失效
标题翻译：通过与血液成分缀合，保护内源性治疗肽免受肽酶活性的影响
公开(公告)号：US06849714B1
公开(公告)日：2005-02-01
申请号：US09623548
申请日：2000-05-17
申请人： Dominique P. Bridon , Alan M. Ezrin , Peter G. Milner , Darren L. Holmes , Karen Thibaudeau
发明人： Dominique P. Bridon , Alan M. Ezrin , Peter G. Milner , Darren L. Holmes , Karen Thibaudeau
IPC分类号： A61K38/00 , C07K1/107 , C07K17/00
CPC分类号： C07K1/1077 , A61K38/00 , Y02P20/55
摘要： A method of synthesizing a modified therapeutic peptide capable of forming a peptidase-stabilized therapeutic peptide conjugate, the peptide having between 3 and 50 amino acids, is k. In a first step of the method, a therapeutic peptide having a carboxy terminal amino acid and amino terminal amino acid is synthesized. In a second step, pairs of cysteine residues present in the therapeutic peptide are sequentially and selectively oxidized to form disulfide bridges in the therapeutic peptide. In a third step, a protecting group is attached to remaining cysteine residues that do not form disulfide bridges in the therapeutic peptide. Finally, the peptide is coupled to a reactive group capable of reacting with amino groups, hydroxyl groups or thiol groups on a blood component to form a covalent bond therewith.
摘要翻译：描述了能够形成肽酶稳定的治疗性肽缀合物的修饰的治疗肽的方法，所述肽具有3至50个氨基酸。在该方法的第一步中，合成具有羧基末端氨基酸和氨基末端氨基酸的治疗肽。在第二步中，存在于治疗肽中的成对的半胱氨酸残基被顺序地和选择性氧化，以在治疗肽中形成二硫键。在第三步中，将保护基连接到在治疗肽中不形成二硫键的剩余半胱氨酸残基。最后，肽与能够与血液成分上的氨基，羟基或硫醇基反应以形成与其共价键的反应性基团偶联。

6. 发明授权

US06329336B1 Long lasting insulinotropic peptides 失效
标题翻译：持久的促胰岛素肽
公开(公告)号：US06329336B1
公开(公告)日：2001-12-11
申请号：US09623618
申请日：2000-09-05
申请人： Dominique P. Bridon , Benoit L'Archeveque , Alan M. Ezrin , Darren L. Holmes , Anouk Leblanc , Serge St. Pierre
发明人： Dominique P. Bridon , Benoit L'Archeveque , Alan M. Ezrin , Darren L. Holmes , Anouk Leblanc , Serge St. Pierre
IPC分类号： A01N3718
CPC分类号： C07K14/005 , A61K38/00 , C07K14/605 , C12N2740/16122
摘要： Modified insulinotropic peptides are disclosed. The modified insulinotropic peptides are capable of forming a peptidase stabilized insulinotropic peptide. The modified insulinotropic peptides are capable of forming covalent bonds with one or more blood components to form a conjugate. The conjugates may be formed in vivo or ex vivo. The modified peptides are administered to treat humans with diabetes and other related diseases.
摘要翻译：公开了改进的促胰岛素肽。修饰的促胰岛素肽能够形成肽酶稳定的促胰岛素肽。修饰的促胰岛素肽能够与一种或多种血液成分形成共价键以形成缀合物。缀合物可以在体内或离体形成。施用修饰的肽以治疗患有糖尿病和其他相关疾病的人。

7. 发明授权

US06437092B1 Conjugates of opioids and endogenous carriers 失效
标题翻译：阿片样物质和内源性载体的结合物
公开(公告)号：US06437092B1
公开(公告)日：2002-08-20
申请号：US09445986
申请日：1999-12-16
申请人： Alan M. Ezrin , Dominique P. Bridon , Darren L. Holmes , Peter G. Milner
发明人： Alan M. Ezrin , Dominique P. Bridon , Darren L. Holmes , Peter G. Milner
IPC分类号： C07K700
CPC分类号： C07K14/70 , A61K38/00 , A61K47/64 , C07K14/665 , C07K2319/00
摘要： Conjugated are prepared from antinociceptive a agents, particularly opioids or opioid analoges, more particularly deltorphins, enkephalins or analogs thereof, by combining said antinociceptive agent with a material providing a functionally reactive group capable of reacting with a blood component (preferably cell or protein). Said conjugates permit extension of the therapeutic life of the antinociceptive agent. They may be administered to patients to alleviate pain, produce analgesic effects, or assist in cases of narcotics withdrawal, and may also be used as probes for receptor activity. The administration to the patient ma be made either in vivo or ex vivo and may be performed by either introducing the derivative including the reactive functional group into the patient's vascular system or preparing such a conjugate externally (or in vitro) and introducing that conjugate to the patient's vascular system.
摘要翻译：通过将所述抗伤害感受剂与提供能够与血液成分（优选细胞或蛋白质）反应的功能反应性基团的材料组合，由抗感受伤害性药物，特别是阿片样物质或阿片样物质类似物，特别是去角质素，脑啡肽或类似物制备缀合物。所述缀合物允许延长抗伤害感受剂的治疗寿命。可以向患者施用以缓解疼痛，产生镇痛作用或辅助麻醉药物撤出的情况，也可用作受体活性的探针。对患者的给药可以在体内或离体制备，并且可以通过将包含反应性官能团的衍生物引入患者的血管系统中或者从外部（或体外）引入该缀合物并将该缀合物引入到患者血管系统。

8. 发明授权

US06887849B2 Long lasting synthetic glucagon-like peptide {GLP-1} 失效
标题翻译：长效合成胰高血糖素样肽（GLP-1）
公开(公告)号：US06887849B2
公开(公告)日：2005-05-03
申请号：US10288340
申请日：2002-11-04
申请人： Dominique P. Bridon , Benoit L'Archeveque , Alan M. Ezrin , Darren L. Holmes , Anouk Leblanc , Serge St. Pierre
发明人： Dominique P. Bridon , Benoit L'Archeveque , Alan M. Ezrin , Darren L. Holmes , Anouk Leblanc , Serge St. Pierre
IPC分类号： A61K38/00 , C07K14/16 , C07K14/605 , A61K38/16 , C07K17/00 , C07K17/02 , C07K17/06
CPC分类号： C07K14/005 , A61K38/00 , A61K47/643 , C07K14/57563 , C07K14/605 , C12N2740/16122
摘要： Modified insulinotropic peptides are disclosed. The modified insulinotropic peptides are capable of forming a peptidase stabilized insulinotropic peptide. The modified insulinotropic peptides are capable of forming covalent bonds with one or more blood components to form a conjugate. The conjugates may be formed in vivo or ex vivo. The modified peptides are administered to treat humans with diabetes and other related diseases.
摘要翻译：公开了改进的促胰岛素肽。修饰的促胰岛素肽能够形成肽酶稳定的促胰岛素肽。修饰的促胰岛素肽能够与一种或多种血液成分形成共价键以形成缀合物。缀合物可以在体内或离体形成。施用修饰的肽以治疗患有糖尿病和其他相关疾病的人。

9. 发明授权

US06706892B1 Pulmonary delivery for bioconjugation 失效
公开(公告)号：US06706892B1
公开(公告)日：2004-03-16
申请号：US09656121
申请日：2000-09-06
申请人： Alan M. Ezrin , Angelica Fleser , Martin Robitaille , Peter G. Milner , Dominique P. Bridon
发明人： Alan M. Ezrin , Angelica Fleser , Martin Robitaille , Peter G. Milner , Dominique P. Bridon
IPC分类号： A61K314015
CPC分类号： A61K9/0075 , A61K47/50 , A61K47/643
摘要： Methods of and compositions for pulmonary delivery of therapeutic agents which are capable of forming covalent bonds with a site of interest or which have formed a covalent bond with a pulmonary solution protein are disclosed. Therapeutic agents useful in the invention include wound healing agents, antibiotics, anti-inflammatories, anti-oxidants, anti-proliferatives, immunosupressants, anti-infective and anti-cancer agents.

10. 发明授权

US06821949B2 Long lasting synthetic glucagon-like peptide (GLP-1) 失效
标题翻译：长效合成胰高血糖素样肽（GLP-1）
公开(公告)号：US06821949B2
公开(公告)日：2004-11-23
申请号：US10287892
申请日：2002-11-04
申请人： Dominique P. Bridon , Benoit L'Archeveque , Alan M. Ezrin , Darren L. Holmes , Anouk Leblanc , Serge St. Pierre
发明人： Dominique P. Bridon , Benoit L'Archeveque , Alan M. Ezrin , Darren L. Holmes , Anouk Leblanc , Serge St. Pierre
IPC分类号： A61K3800
CPC分类号： C07K14/005 , A61K38/00 , A61K47/643 , C07K14/57563 , C07K14/605 , C12N2740/16122
摘要： Modified insulinotropic peptides are disclosed. The modified insulinotropic peptides are capable of forming a peptidase stabilized insulinotropic peptide. The modified insulinotropic peptides are capable of forming covalent bonds with one or more blood components to form a conjugate. The conjugates may be formed in vivo or ex vivo. The modified peptides are administered to treat humans with diabetes and other related diseases.
摘要翻译：公开了改进的促胰岛素肽。修饰的促胰岛素肽能够形成肽酶稳定的促胰岛素肽。修饰的促胰岛素肽能够与一种或多种血液成分形成共价键以形成缀合物。缀合物可以在体内或离体形成。施用修饰的肽以治疗患有糖尿病和其他相关疾病的人。

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