公开(公告)号：WO1995013830A1

公开(公告)日：1995-05-26

申请号：PCT/US1994013343

申请日：1994-11-17

Applicant: MASSACHUSETTS INSTITUTE OF TECHNOLOGY ,  CHILDREN'S MEDICAL CENTER CORPORATION

Inventor： MASSACHUSETTS INSTITUTE OF TECHNOLOGY ,  CHILDREN'S MEDICAL CENTER CORPORATION ,  SASISEKHARAN, Ramnath ,  MOSES, Marsha, A. ,  NUGENT, Matthew, A. ,  COONEY, Charles, L. ,  LANGER, Robert, S.

IPC: A61K38/51

CPC classification number: C12N9/88 ,  A61K38/00

Abstract: Pharmaceutical compositions for delivering an effective dose to a desired site of a heparinase. These compositions are based on the discovery that heparinase alone can inhibit angiogenesis. The effective dosage is dependent not only on the heparinase, but also on the method and means of delivery, which can be localized or systemic. For example, in some applications, as in the treatment of psoriasis or diabetic retinopathy, the inhibitor is delivered in a topical ophthalmic carrier. In other applications, as in the treatment of solid tumors, the inhibitor is delivered by means of a biodegradable, polymeric implant.

Abstract translation: 用于将有效剂量递送至肝素酶的所需位点的药物组合物。 这些组合物基于单独的肝素酶可以抑制血管发生的发现。 有效剂量不仅取决于肝素酶，而且还取决于递送的方法和手段，其可以是局部的或全身性的。 例如，在一些应用中，如在牛皮癣或糖尿病性视网膜病变的治疗中，抑制剂在局部眼科载体中递送。 在其他应用中，如在实体瘤的治疗中，抑制剂通过可生物降解的聚合物植入物递送。

公开(公告)号：WO1994012618A1

公开(公告)日：1994-06-09

申请号：PCT/US1993011541

申请日：1993-11-30

Applicant: MASSACHUSETTS INSTITUTE OF TECHNOLOGY ,  UNIVERSITY OF IOWA RESEARCH FOUNDATION

Inventor： MASSACHUSETTS INSTITUTE OF TECHNOLOGY ,  UNIVERSITY OF IOWA RESEARCH FOUNDATION ,  SASISEKHARAN, Ramnath ,  LOHSE, Daniel, L. ,  COONEY, Charles, L. ,  LINHARDT, Robert, J. ,  LANGER, Robert, S.

IPC: C12N09/00

CPC classification number: C12N9/88 ,  Y10S435/822 ,  Y10S435/85

Abstract: A single, reproducible scheme to simultaneously purify all three of the heparin lyases from F. heparinum to apparent homogeneity is disclosed herein. The kinetic properties of the heparin lyases have been determined as well as the conditions to optimize their activity and stability. Monoclonal antibodies to the three heparinases are also described and are useful for detection, isolation and characterization of the heparinases.

Abstract translation: 本文公开了将来自肝素肝素的所有三种肝素裂解酶同时纯化到表观均一性的单一可再现方案。 已经确定了肝素裂解酶的动力学性质以及优化其活性和稳定性的条件。 还描述了三种肝素酶的单克隆抗体，并且其可用于肝素酶的检测，分离和表征。

公开(公告)号：WO1993008289A1

公开(公告)日：1993-04-29

申请号：PCT/US1992009124

申请日：1992-10-22

Applicant: MASSACHUSETTS INSTITUTE OF TECHNOLOGY

Inventor： MASSACHUSETTS INSTITUTE OF TECHNOLOGY ,  SASISEKHARAN, Ramnath ,  MOREMEN, Kelley ,  COONEY, Charles, L. ,  ZIMMERMANN, Joseph, J. ,  LANGER, Robert, S.

IPC: C12N15/60

CPC classification number: C12N9/88

Abstract: The cloning of the heparinase gene from Flavobacterium Heparinum using the polymerase chain reaction is described. The Open Reading Frame (ORF) corresponded to 1152 base pairs encoding a precursor protein of MW 43,800 daltons. The amino acid sequence reveals a 20-residue leader peptide. The gene was expressed in two expression systems in E. Coli.

Abstract translation: 描述了使用聚合酶链反应从肝炎杆菌中克隆肝素酶基因。 开放阅读框（ORF）对应于编码MW 43,800道尔顿的前体蛋白质的1152个碱基对。 氨基酸序列显示20个残基的前导肽。 该基因在大肠杆菌的两个表达系统中表达。

公开(公告)号：EP0726773A1

公开(公告)日：1996-08-21

申请号：EP95902610.0

申请日：1994-11-17

Applicant: MASSACHUSETTS INSTITUTE OF TECHNOLOGY ,  CHILDREN'S MEDICAL CENTER CORPORATION

Inventor： SASISEKHARAN, Ramnath ,  MOSES, Marsha A. ,  NUGENT, Matthew A. ,  COONEY, Charles L. ,  LANGER, Robert S.

IPC: A61K47 ,  A61K35 ,  A61K38 ,  A61P9 ,  A61P17 ,  A61P27 ,  A61P35 ,  C12N9

CPC classification number: C12N9/88 ,  A61K38/00

Abstract: Pharmaceutical compositions for delivering an effective dose to a desired site of a heparinase. These compositions are based on the discovery that heparinase alone can inhibit angiogenesis. The effective dosage is dependent not only on the heparinase, but also on the method and means of delivery, which can be localized or systemic. For example, in some applications, as in the treatment of psoriasis or diabetic retinopathy, the inhibitor is delivered in a topical ophthalmic carrier. In other applications, as in the treatment of solid tumors, the inhibitor is delivered by means of a biodegradable, polymeric implant.

公开(公告)号：EP0670892B1

公开(公告)日：2005-06-22

申请号：EP94902450.9

申请日：1993-11-30

Applicant: MASSACHUSETTS INSTITUTE OF TECHNOLOGY ,  UNIVERSITY OF IOWA RESEARCH FOUNDATION

Inventor： SASISEKHARAN, Ramnath ,  LOHSE, Daniel L. ,  COONEY, Charles L. ,  LINHARDT, Robert J. ,  LANGER, Robert S.

IPC: C12N9/88

CPC classification number: C12N9/88 ,  Y10S435/822 ,  Y10S435/85

Abstract: A single, reproducible scheme to simultaneously purify all three of the heparin lyases from F. heparinum to apparent homogeneity is disclosed herein. The kinetic properties of the heparin lyases have been determined as well as the conditions to optimize their activity and stability. Monoclonal antibodies to the three heparinases are also described and are useful for detection, isolation and characterization of the heparinases.

公开(公告)号：EP0670892A1

公开(公告)日：1995-09-13

申请号：EP94902450.0

申请日：1993-11-30

Applicant: MASSACHUSETTS INSTITUTE OF TECHNOLOGY ,  UNIVERSITY OF IOWA RESEARCH FOUNDATION

Inventor： SASISEKHARAN, Ramnath ,  LOHSE, Daniel L. ,  COONEY, Charles L. ,  LINHARDT, Robert J. ,  LANGER, Robert S.

IPC: G01N33 ,  C07K16 ,  C12N9 ,  C12P19 ,  C12P21 ,  C12R1

CPC classification number: C12N9/88 ,  Y10S435/822 ,  Y10S435/85

Abstract: A single, reproducible scheme to simultaneously purify all three of the heparin lyases from F. heparinum to apparent homogeneity is disclosed herein. The kinetic properties of the heparin lyases have been determined as well as the conditions to optimize their activity and stability. Monoclonal antibodies to the three heparinases are also described and are useful for detection, isolation and characterization of the heparinases.

公开(公告)号：EP0610408A1

公开(公告)日：1994-08-17

申请号：EP92923556.0

申请日：1992-10-22

Applicant: MASSACHUSETTS INSTITUTE OF TECHNOLOGY

Inventor： SASISEKHARAN, Ramnath ,  MOREMEN, Kelley ,  COONEY, Charles, L. ,  ZIMMERMANN, Joseph, J. ,  LANGER, Robert, S.

IPC: C12N15 ,  C12N1 ,  C12N9 ,  C12R1

CPC classification number: C12N9/88

Abstract: Clonage du gène codant l'héparinase exprimé dans Flavobacterium Heparinum à l'aide de l'amplification enzymatique du génome. Le cadre de lecture ouvert correspondait à 1152 paires de bases codant une protéine précurseur d'un poids moléculaire de 43.800 daltons. La séquence d'acides aminés révèle un peptide leader à 20 restes. Ledit gène a été exprimé dans deux systèmes d'expression de E. Coli.