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    PROCESS FOR THE SYNTHESIS OF CONJUGATES OF GLYCOSAMINOGLYCANES (GAG) WITH BIOLOGICALLY ACTIVE MOLECULES, POLYMERIC CONJUGATES AND RELATIVE USES THEREOF
    4.
    发明申请
    PROCESS FOR THE SYNTHESIS OF CONJUGATES OF GLYCOSAMINOGLYCANES (GAG) WITH BIOLOGICALLY ACTIVE MOLECULES, POLYMERIC CONJUGATES AND RELATIVE USES THEREOF 审中-公开
    合成具有生物活性分子的糖蛋白氨基酸（GAG）结合的方法，聚合物共聚物及其相关用途

    公开(公告)号：WO2010145821A1

    公开(公告)日：2010-12-23

    申请号：PCT/EP2010/003634

    申请日：2010-06-04

    Applicant: FIDIA FARMACEUTICI S.P.A. ,  D'ESTE, Matteo ,  RENIER, Davide ,  PASUT, Gianfranco ,  ROSATO, Antonio

    Inventor： D'ESTE, Matteo ,  RENIER, Davide ,  PASUT, Gianfranco ,  ROSATO, Antonio

    IPC: C08B37/00

    CPC classification number: C08B37/0072 ,  A61K31/726 ,  C08B37/0063 ,  C08B37/0069 ,  C08B37/0075

    Abstract: The present invention relates to a process for the synthesis of conjugates of glycosaminoglycanes (GAG) with biologically active molecules of varying nature, comprising small molecules and macro-molecules. In particular, the present invention relates to the conjugation of hyaluronic acid (HA) and its derivatives with polypeptides and proteins with a biological action, such as, for example, interferons, erythropoietins, growth factors, insulin, cytokines, antibodies and hormones. An object of the present invention also relates to isolatable intermediates obtained by the partial or total reaction of GAG with protected amino aldehydes in the conjugation process mentioned above.

    Abstract translation: 本发明涉及一种用于合成糖胺聚糖（GAG）与不同性质的生物活性分子的缀合物的方法，其包含小分子和大分子。 特别地，本发明涉及透明质酸（HA）及其衍生物与具有生物作用的多肽和蛋白质（例如干扰素，促红细胞生成素，生长因子，胰岛素，细胞因子，抗体和激素）的缀合。 本发明的目的还涉及通过上述共轭方法中GAG与被保护的氨基醛的部分或全部反应获得的可分离的中间体。

    POLYMERIC CONJUGATES OF PHOSPHOLIPIDS
    5.
    发明申请
    POLYMERIC CONJUGATES OF PHOSPHOLIPIDS 审中-公开
    磷脂的聚合物

    公开(公告)号：WO2010143218A1

    公开(公告)日：2010-12-16

    申请号：PCT/IT2010/000258

    申请日：2010-06-09

    Applicant: UNIVERSITÀ DEGLI STUDI DI PADOVA ,  PASUT, Gianfranco ,  SCHIAVON, Oddone ,  VERONESE, Francesco

    Inventor： PASUT, Gianfranco ,  SCHIAVON, Oddone ,  VERONESE, Francesco

    IPC: A61K47/48 ,  A61K9/127 ,  C08G83/00

    CPC classification number: A61K9/1273

    Abstract: The present invention regards new polymeric conjugates of phospholipids comprehending at least a polymer conjugated, through a branched molecule, at least to two phospholipids, and their use, as such or in combination, with other amphypatic substances to deliver biologically active agents. The above reported new polymer-phospholipids conjugates can be used in preparations, 'kits', formulation of liposomes, for diagnostic application or in therapy.

    Abstract translation: 本发明涉及磷脂的新型聚合物缀合物，其包括至少一种通过支链分子缀合至少两个磷脂的聚合物，以及它们与其它amphypatic物质一起或组合用于递送生物活性剂的用途。 上述报道的新型聚合物 - 磷脂缀合物可用于制备“试剂盒”，脂质体制剂，用于诊断应用或治疗。

    NEW ACTIVATED POLY(ETHYLENE GLYCOLS) AND RELATED POLYMERS AND THEIR APPLICATIONS
    6.
    发明申请
    NEW ACTIVATED POLY(ETHYLENE GLYCOLS) AND RELATED POLYMERS AND THEIR APPLICATIONS 审中-公开
    新型活性聚（乙烯甘油）及相关聚合物及其应用

    公开(公告)号：WO2007112794A1

    公开(公告)日：2007-10-11

    申请号：PCT/EP2006/070265

    申请日：2006-12-29

    Applicant: KERYOS SPA ,  VERONESE, Francesco Maria ,  PASUT, Gianfranco ,  TONON, Giancarlo ,  SCHREPFER, RODOLFO

    Inventor： VERONESE, Francesco Maria ,  PASUT, Gianfranco ,  TONON, Giancarlo ,  SCHREPFER, RODOLFO

    IPC: C08G65/329 ,  A61K47/48

    CPC classification number: C08G65/329 ,  A61K47/60 ,  C07K1/1077 ,  C08G65/333

    Abstract: There are disclosed chemically active poly(ethylene glycols) and other hydrophilic polymers that are suitable for coupling to pharmaceutically or diagnostically active agents such as peptides, oligonucleotides, proteins or non- peptide molecules. The compounds are represented by the formula Poly-(X-NH-CO-A) n wherein: Poly is a hydrophilic polymer having a molecular weight of from about 300 to 100000 Daltons; A together with -NH-CO- forms a reactive group; X is a spacer moiety or a bond; n is an integer comprised between 1 and 50. The active agents of interest which may be conjugated to the disclosed compounds may be selected from hemoglobin, insulin, urokinase, alpha- interferon, G-CSF, hGH, asparaginase, adenosine deaminase, superoxide dismutase and catalase.

    Abstract translation: 公开了化学活性聚（乙二醇）和其它亲水性聚合物，其适于与药学或诊断活性剂如肽，寡核苷酸，蛋白质或非肽分子偶联。 所述化合物由下式表示：Poly-（X-NH-CO-A）n N n其中：Poly是分子量为约300至100000道尔顿的亲水性聚合物; A与-NH-CO-一起形成反应性基团; X是间隔部分或键; 可以与所公开的化合物缀合的感兴趣的活性剂可以选自血红蛋白，胰岛素，尿激酶，α-干扰素，G-CSF，hGH，天冬酰胺酶，腺苷脱氨酶，超氧化物歧化酶 和过氧化氢酶。

    POLYMERIC CONJUGATES CONTAINING PHOSPHINE - BASED CHELATING GROUPS
    7.
    发明申请
    POLYMERIC CONJUGATES CONTAINING PHOSPHINE - BASED CHELATING GROUPS 审中-公开
    含聚磷酸酯基团的聚合物

    公开(公告)号：WO2005011738A3

    公开(公告)日：2005-04-14

    申请号：PCT/IT2004000422

    申请日：2004-07-29

    Applicant: UNIV PADOVA ,  VERONESE FRANCESCO ,  MAZZI ULDERICO ,  PASUT GIANFRANCO ,  VISENTIN ROBERTA

    Inventor： VERONESE FRANCESCO ,  MAZZI ULDERICO ,  PASUT GIANFRANCO ,  VISENTIN ROBERTA

    IPC: A61K47/48 ,  A61K49/12 ,  A61K51/06

    CPC classification number: A61K51/065 ,  A61K47/60 ,  A61K49/085 ,  A61K49/126

    Abstract: Reactive polymers can be conjugated, directly or by means of linkers and/or others polymers to chelating agents comprising at least one phosphorous atom in the form of a phosphine or phosphine oxide (or precursors thereof) to form conjugates useful in diagnostic and therapeutic applications. In particular this invention provides conjugates comprising a hydrophilic polymer bound, directly or by means of other moieties, to at least one chelating group able to chelate metal radioisotopes comprising at least one phosphine or one phosphine oxide phosphorous. Such chelating groups can be conjugated to the hydrophilic polymer directly or via one or more linkers and/or one or more additional polymers. The use of additional polymers can provide increased loading of chelating agent. The linkers are preferably selected among alkyl groups or aromatic groups or cleavable peptides or other biodegradable sequences. Additionally, one or more targeting molecules can be linked to the hydrophilic polymer directly or by means of linkers and/or others polymers. Due to their polymeric structure, the conjugates according to the invention have enhanced specificity toward certain tissues, such as tumors, inflamed tissued and the liver. The specificity can be further increased by the additional provision of targeting moieties such as antibodies or sugars. These conjugates can be formulated for remaining in the blood circulation for a period for time suitable for diagnostic and therapeutic applications. Moreover they possess thermodynamic and kinetic stability, keeping the metal chelate intact under physiological conditions. The invention also provides a very simple and efficient method for the labelling of radiopharmaceuticals, which avoids the use of any additional reducing agent. Accordingly, metal ions like technetium or rhenium can be added as pertechnetate or pherrhenate to chelating agents comprising polymer and a phosphine and surprisingly it has been found that such chelating agents can act as reducing agents of the metal and the use of an additional reducing agent is not necessary. This allows the preparation of simple kits comprising a component (a) comprising the polymeric chelating agent and a component (b) comprising the metal ion in its highest oxidation state. These two components can be kept separately and combined together just before use to yield the metal complex without the need of further reducing step and purification.

    Abstract translation: 反应性聚合物可以直接或通过接头和/或其它聚合物与螯合剂共轭，所述螯合剂包含至少一种磷化氢或氧化膦（或其前体）形式的磷原子，以形成可用于诊断和治疗应用的缀合物。 特别地，本发明提供了缀合物，其包含直接或通过其它部分结合至少一个能够螯合包含至少一个膦或一种氧化膦磷的金属放射性同位素的螯合基团的亲水性聚合物。 这样的螯合基团可以直接或通过一种或多种接头和/或一种或多种另外的聚合物与亲水性聚合物缀合。 使用另外的聚合物可以提供增加螯合剂的负载量。 连接体优选选自烷基或芳族基团或可切割肽或其它可生物降解的序列。 另外，一个或多个靶向分子可以直接或通过接头和/或其它聚合物与亲水性聚合物连接。 由于其聚合物结构，根据本发明的缀合物对某些组织（例如肿瘤，发炎组织和肝脏）具有增强的特异性。 可以通过额外提供靶向部分例如抗体或糖来进一步提高特异性。 这些缀合物可以配制用于在血液循环中保持一段适合诊断和治疗应用的时间。 此外，它们具有热力学和动力学稳定性，在生理条件下保持金属螯合物完整。 本发明还提供了用于放射性药物标记的非常简单和有效的方法，其避免使用任何另外的还原剂。 因此，可以将诸如锝或铼的金属离子作为高锝酸盐或苯乙烯酸盐加入到包含聚合物和膦的螯合剂中，并且令人惊讶地发现，这种螯合剂可以作为金属的还原剂，并且使用另外的还原剂是 不必要。 这允许制备包含包含聚合物螯合剂的组分（a）和包含其最高氧化态的金属离子的组分（b）的简单试剂盒。 这两种组分可以在使用前分开保存并组合在一起以产生金属络合物，而不需要进一步的还原步骤和纯化。

    POLYMERIC CONJUGATES FOR DIAGNOSIS AND THERAPY
    8.
    发明申请
    POLYMERIC CONJUGATES FOR DIAGNOSIS AND THERAPY 审中-公开
    聚合物用于诊断和治疗

    公开(公告)号：WO2005011738A2

    公开(公告)日：2005-02-10

    申请号：PCT/IT2004/000422

    申请日：2004-07-29

    Applicant: UNIVERSITÀ DEGLI STUDI DI PADOVA ,  VERONESE, Francesco ,  MAZZI, Ulderico ,  PASUT, Gianfranco ,  VISENTIN, Roberta

    Inventor： VERONESE, Francesco ,  MAZZI, Ulderico ,  PASUT, Gianfranco ,  VISENTIN, Roberta

    IPC: A61K47/00

    CPC classification number: A61K51/065 ,  A61K47/60 ,  A61K49/085 ,  A61K49/126

    Abstract: Reactive polymers can be conjugated, directly or by means of linkers and/or others polymers to chelating agents comprising at least one phosphorous atom in the form of a phosphine or phosphine oxide (or precursors thereof) to form conjugates useful in diagnostic and therapeutic applications. In particular this invention provides conjugates comprising a hydrophilic polymer bound, directly or by means of other moieties, to at least one chelating group able to chelate metal radioisotopes comprising at least one phosphine or one phosphine oxide phosphorous. Such chelating groups can be conjugated to the hydrophilic polymer directly or via one or more linkers and/or one or more additional polymers. The use of additional polymers can provide increased loading of chelating agent. The linkers are preferably selected among alkyl groups or aromatic groups or cleavable peptides or other biodegradable sequences. Additionally, one or more targeting molecules can be linked to the hydrophilic polymer directly or by means of linkers and/or others polymers. Due to their polymeric structure, the conjugates according to the invention have enhanced specificity toward certain tissues, such as tumors, inflamed tissued and the liver. The specificity can be further increased by the additional provision of targeting moieties such as antibodies or sugars. These conjugates can be formulated for remaining in the blood circulation for a period for time suitable for diagnostic and therapeutic applications. Moreover they possess thermodynamic and kinetic stability, keeping the metal chelate intact under physiological conditions. The invention also provides a very simple and efficient method for the labelling of radiopharmaceuticals, which avoids the use of any additional reducing agent. Accordingly, metal ions like technetium or rhenium can be added as pertechnetate or pherrhenate to chelating agents comprising polymer and a phosphine and surprisingly it has been found that such chelating agents can act as reducing agents of the metal and the use of an additional reducing agent is not necessary. This allows the preparation of simple kits comprising a component (a) comprising the polymeric chelating agent and a component (b) comprising the metal ion in its highest oxidation state. These two components can be kept separately and combined together just before use to yield the metal complex without the need of further reducing step and purification.

    Abstract translation: 反应性聚合物可以直接或通过接头和/或其它聚合物与螯合剂共轭，所述螯合剂包含至少一种磷化氢或氧化膦（或其前体）形式的磷原子以形成用于诊断和治疗应用的缀合物。 特别地，本发明提供了包含直接或通过其它部分结合至少一个能够螯合包含至少一个膦或一种氧化膦磷的金属放射性同位素的至少一种螯合基团的亲水性聚合物的缀合物。 这样的螯合基团可以直接或通过一种或多种接头和/或一种或多种另外的聚合物与亲水聚合物缀合。 使用额外的聚合物可以提供增加螯合剂的负载量。 连接体优选选自烷基或芳族基团或可切割肽或其它可生物降解的序列。 另外，一个或多个靶向分子可以直接或通过接头和/或其它聚合物与亲水性聚合物连接。 由于其聚合物结构，根据本发明的缀合物对某些组织（例如肿瘤，发炎组织和肝脏）具有增强的特异性。 可以通过额外提供靶向部分例如抗体或糖来进一步提高特异性。 这些缀合物可以配制用于在血液循环中保持一段适合于诊断和治疗应用的时间。 此外，它们具有热力学和动力学稳定性，在生理条件下保持金属螯合物完整。 本发明还提供了一种用于标记放射性药物的非常简单和有效的方法，其避免使用任何另外的还原剂。 因此，可以将诸如锝或铼的金属离子作为高锝酸盐或苯乙烯酸酯加入到包含聚合物和膦的螯合剂中，并且令人惊讶地发现，这种螯合剂可以用作金属的还原剂，并且使用另外的还原剂是 不必要。 这允许制备包含包含聚合物螯合剂的组分（a）和包含其最高氧化态的金属离子的组分（b）的简单试剂盒。 这两种组分可以在使用前分开保存并组合在一起以产生金属络合物，而不需要进一步的还原步骤和纯化。

    POLYETHYLENE GLYCOL CONJUGATES RELEASING NITRIC OXIDE
    9.
    发明申请
    POLYETHYLENE GLYCOL CONJUGATES RELEASING NITRIC OXIDE 审中-公开
    聚乙二醇共聚物释放氮氧化物

    公开(公告)号：WO2004089420A1

    公开(公告)日：2004-10-21

    申请号：PCT/IB2004/001080

    申请日：2004-04-06

    Applicant: BIOPEG LTD. ,  VERONESE, Francesco ,  PASUT, Gianfranco

    Inventor： VERONESE, Francesco ,  PASUT, Gianfranco

    IPC: A61K47/48

    CPC classification number: A61K47/60

    Abstract: The present invention relates to polyethylene glycol derivatives having a controlled release nitric oxide as well as their use as drugs. It has been surprisingly found that is possible connect physically or by chemical bonds polyethylene glycol nitrate with pharmacologically active molecules, such as anti-inflammatory, antitumoral drugs, peptides, proteins and oligonucleotides thus obtaining compounds having a better activities profile.

    Abstract translation: 本发明涉及具有控制释放一氧化氮的聚乙二醇衍生物及其作为药物的用途。 已经令人惊奇地发现，可能物理连接或通过化学键与聚乙二醇硝酸盐与药理学活性分子例如抗炎，抗肿瘤药物，肽，蛋白质和寡核苷酸连接，从而获得具有更好活性概况的化合物。

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