公开(公告)号：WO1993014778A1

公开(公告)日：1993-08-05

申请号：PCT/US1993000492

申请日：1993-01-21

Applicant: VICAL, INC.

Inventor： VICAL, INC. ,  RHODES, Gary, H. ,  DWARKI, Varavani, J. ,  FELGNER, Philip, L. ,  HWANG-FELGNER, Jiin-Yu ,  MANTHORPE, Marston

IPC: A61K37/00

CPC classification number: A61K38/57 ,  A61K9/1272 ,  A61K35/12 ,  A61K38/00 ,  A61K38/185 ,  A61K39/0003 ,  A61K39/12 ,  A61K39/21 ,  A61K48/00 ,  A61K2039/5156 ,  A61K2039/53 ,  A61K2039/55555 ,  C07K14/48 ,  C12N2740/16134

Abstract: A method for delivering a polypeptide to the interior of a cell of a vertebrate ex vivo is provided comprising the steps of: removing live cells from the vertebrate, contacting the cells with a preparation comprising an effective amount of polynucleotide operatively coding for the polypeptide and lipid effective to deliver the polynucleotide in the cells; and freezing or returning the cells to the vertebrate within 48 hours after the contacting step so that the cells express the polynucleotide in vivo. The method additionally can comprise substantially separating the cells from the surrounding extracellular matrix.

Abstract translation: 提供了一种将多肽递送到离体脊椎动物细胞内部的方法，包括以下步骤：从脊椎动物中除去活细胞，使细胞与包含有效量的可操作地编码多肽和脂质的多核苷酸的制剂接触 有效地将细胞中的多核苷酸递送; 并且在接触步骤后48小时内将细胞冷冻或返回到脊椎动物，使得细胞在体内表达多核苷酸。 该方法另外可以包括基本上将细胞与周围细胞外基质分离。

公开(公告)号：WO1991017424A1

公开(公告)日：1991-11-14

申请号：PCT/US1991002962

申请日：1991-04-29

Applicant: VICAL, INC.

Inventor： VICAL, INC. ,  FELGNER, Philip, L.

IPC: G01N21/00

CPC classification number: A61K9/1271 ,  A61K9/1272

Abstract: Disclosed are methods and compositions for facilitating intracellular delivery of biologically active substances of pharmaceutical agents, comprising self-assembling complexes of positively and negatively charged lipid species capable of interacting with a substance to be delivered. The assembled complexes have a net positive charge suitable for spontaneously attaching to negatively charged cell membranes, and may comprise a neutral or positively charged bioactive substance first encapsulated in or complexed with negatively charged lipid vesicles which are next complexed with cationic lipid vesicles having a net positive charge before or in the process of administration to the cell.

Abstract translation: 公开了用于促进药物的生物活性物质的细胞内递送的方法和组合物，包括能够与待递送物质相互作用的带正电荷和带负电荷的脂质物质的自组装复合物。 组装的复合物具有适合于自发附着到带负电荷的细胞膜的净正电荷，并且可以包含首先包封在带负电荷的脂质囊泡中或与带负电荷的脂质囊泡络合的中性或带正电荷的生物活性物质，其随后与具有净阳性的阳离子脂质囊泡复合 在给予细胞前或给药过程中进行电荷注射。

公开(公告)号：WO1991016024A1

公开(公告)日：1991-10-31

申请号：PCT/US1991002691

申请日：1991-04-18

Applicant: VICAL, INC.

Inventor： VICAL, INC. ,  FELGNER, Philip, L. ,  KUMAR, Raj ,  BASAVA, Channa ,  BORDER, Richard, C. ,  HWANG-FELGNER, Jiin-Yu

IPC: A61F13/00

CPC classification number: C12N15/88 ,  A61K9/0014 ,  A61K9/0019 ,  A61K9/1272 ,  A61K47/186 ,  A61K47/54 ,  A61K47/544 ,  A61K47/645

Abstract: Disclosed are cationic lipids capable of facilitating transport of biologically active agents into cells, including the transfection of cells by therapeutic polynucleotides, the delivery of antiviral drugs, and the introduction of immunogenic peptides. The cationic lipids, comprising an ammonium group, have general structure (I). Also disclosed are adducts of these compounds comprising additional cationic sites that enhance the transfective or transport activity. Structure-activity correlations provide for the selection of preferred compounds to be synthesized for this purpose. Compositions disclosed for use of these cationic lipids include formulations for in vitro transfection and pharmaceutical formulations for parenteral and topical administration of therapeutic agents.

公开(公告)号：WO1993003709A1

公开(公告)日：1993-03-04

申请号：PCT/US1992004225

申请日：1992-05-19

Applicant: VICAL, INC.

Inventor： VICAL, INC. ,  FELGNER, Philip, L. ,  ABAI, Anna, M. ,  MANTHORPE, Marston, C.

IPC: A61K09/127

CPC classification number: C07K14/4712 ,  A61K9/1271 ,  A61K9/1272 ,  A61K38/465 ,  A61K47/543 ,  A61K48/00 ,  C12Y301/21001 ,  A61K2300/00

Abstract: Disclosed is a pharmaceutical composition suitable for the pulmonary administration of therapeutically effective amounts of DNase, a macromolecule operatively coding for a functional protein to remedy the cellular defect associated with cystic fibrosis and sufficient lipid to form cationic complexes with the macromolecule, effective to deliver the macromolecule into pulmonary cells in vivo. Additionally disclosed are methods for the treatment of cystic fibrosis.

Abstract translation: 公开了适用于肺部给予治疗有效量的DNA酶的药物组合物，其是可操作地编码功能性蛋白质的大分子，用于补救与囊性纤维化相关的细胞缺陷和足够的脂质与大分子形成阳离子配合物，有效递送大分子 在体内进入肺细胞。 另外公开了治疗囊性纤维化的方法。

公开(公告)号：WO1990011092A1

公开(公告)日：1990-10-04

申请号：PCT/US1990001515

申请日：1990-03-21

Applicant: VICAL, INC. ,  WISCONSIN ALUMNI RESEARCH FOUNDATION

Inventor： VICAL, INC. ,  WISCONSIN ALUMNI RESEARCH FOUNDATION ,  FELGNER, Philip, L. ,  WOLFF, Jon, Asher ,  RHODES, Gary, H. ,  MALONE, Robert, Wallace ,  CARSON, Dennis, A.

IPC: A61K48/00

CPC classification number: A61K39/00 ,  A61K9/1272 ,  A61K48/00 ,  A61K2039/53 ,  A61K2039/55555 ,  C07K14/005 ,  C07K14/61 ,  C12N9/0069 ,  C12N9/1033 ,  C12N9/1247 ,  C12N9/78 ,  C12N15/87 ,  C12N2740/16122 ,  C12Y113/12007

Abstract: A method for delivering an isolated polynucleotide to the interior of a cell in a vertebrate, comprising the interstitial introduction of an isolated polynucleotide into a tissue of the vertebrate where the polynucleotide is taken up by the cells of the tissue and exerts a therapeutic effect on the vertebrate. The method can be used to deliver a therapeutic polypeptide to the cells of the vertebrate, to provide an immune response upon in vivo translation of the polynucleotide, to deliver antisense polynucleotides, to deliver receptors to the cells of the vertebrate, or to provide transitory gene therapy.

Abstract translation: 一种用于将分离的多核苷酸递送至脊椎动物细胞内部的方法，包括将分离的多核苷酸间插入脊椎动物的组织中，其中所述多核苷酸被组织的细胞吸收并对其施用治疗效果 脊椎动物。 该方法可用于将治疗性多肽递送至脊椎动物的细胞，以在多核苷酸的体内翻译中提供免疫应答，递送反义多核苷酸，将受体递送至脊椎动物的细胞，或提供短暂基因 治疗。