公开(公告)号：US06831070B2

公开(公告)日：2004-12-14

申请号：US09811323

申请日：2001-03-16

Applicant: Michael German ,  Ira D. Goldfine ,  Stephen S. Rothman

Inventor： Michael German ,  Ira D. Goldfine ,  Stephen S. Rothman

IPC: A61K4800

CPC classification number: A61K38/28 ,  A61K38/27 ,  A61K48/00 ,  C07K14/61

Abstract: The present invention provides methods of delivering a secreted protein into the bloodstream of a mammal. A nucleic acid molecule encoding the protein is introduced into the gastrointestinal tract of the mammal, and the nucleic acid molecule enters an intestinal epithelial cell, where the protein is produced and secreted into the bloodstream of the mammal.

Abstract translation: 本发明提供了将分泌蛋白递送到哺乳动物的血液中的方法。 编码蛋白质的核酸分子被引入到哺乳动物的胃肠道中，核酸分子进入肠上皮细胞，其中蛋白质被产生并分泌到哺乳动物的血液中。

公开(公告)号：US06818627B1

公开(公告)日：2004-11-16

申请号：US09485421

申请日：2000-10-05

Applicant: Sundarasamy Mahalingam ,  Velpandi Ayyavoo ,  Mamata Patel ,  Thomas Kieber-Emmons ,  David B. Weiner

Inventor： Sundarasamy Mahalingam ,  Velpandi Ayyavoo ,  Mamata Patel ,  Thomas Kieber-Emmons ,  David B. Weiner

IPC: A61K4800

CPC classification number: C07K14/005 ,  A61K47/64 ,  A61K47/6901 ,  A61K48/00 ,  A61K2039/53 ,  C12N2740/16322 ,  G01N33/56988 ,  G01N2500/00

Abstract: Conjugated compositions comprising a fragment of HIV-1 Vpr or a non-HIV-1 Vpr protein conjugated to a therapeutic compound and methods of using the same to deliver therapeutic compounds to a cell's nucleus or for the preparation of drug delivery particles are disclosed. Functional fragments of HIV-1 Vpr and functional non-HIV-1 Vpr proteins, and pharmaceutical compositions comprising the same are disclosed. Methods of inhibiting cell proliferation and methods of treating an individual who has a hyperproliferative disease are disclosed. Methods of identifying compounds that inhibit Vpr protein binding to the p6 domain of p55 or to p6 protein and kits for performing such methods are disclosed.

Abstract translation: 公开了包含与治疗性化合物缀合的HIV-1Vpr片段或非HIV-1Vpr蛋白的片段的共轭组合物及其使用方法将治疗性化合物递送至细胞核或用于制备药物递送颗粒。 公开了HIV-1Vpr和功能性非HIV-1 Vpr蛋白的功能片段和包含其的药物组合物。 公开了抑制细胞增殖的方法和治疗具有过度增殖性疾病的个体的方法。 公开了鉴定抑制Vpr蛋白与p55或p6蛋白的p6结构域结合的化合物的方法和用于进行这些方法的试剂盒。

公开(公告)号：US06814963B2

公开(公告)日：2004-11-09

申请号：US10050665

申请日：2002-01-16

Applicant: Jyh-Lyh Juang ,  Dung-Fang Lee

Inventor： Jyh-Lyh Juang ,  Dung-Fang Lee

IPC: A61K4800

CPC classification number: C12N15/86 ,  C12N7/00 ,  C12N2710/14121 ,  C12N2710/14143

Abstract: Compositions and methods are provided that relate to a recombinant virus-based vector, e.g., a baculovirus-based vector, that allows the expression of an exogenous target protein in non-permissive cells (e.g., non-permissive insect cells or mammalian cells) in the absence of expression of a detectable selection marker. The vector includes a nucleic acid sequence encoding a detectable selection marker which is controlled by a promoter that is active in host cells used to screen for recombinant virus but is silent in the non-permissive cell used for expression of the exogenous target protein. The vector also includes an exogenous nucleic acid sequence encoding a target protein under the control of a promoter that is active in the non-permissive cell. This system allows the selection marker to be expressed during viral plaque screening, but not while the target protein is being produced.

Abstract translation: 提供的组合物和方法涉及基于重组病毒的载体，例如基于杆状病毒的载体，其允许在非允许细胞（例如，非允许昆虫细胞或哺乳动物细胞）中表达外源靶蛋白 不存在可检测选择标记的表达。 载体包括编码可检测选择标记的核酸序列，其由在用于筛选重组病毒的宿主细胞中有活性但在用于表达外源靶蛋白的非允许细胞中沉默的启动子控制。 载体还包括编码在非允许细胞中有活性的启动子控制下的靶蛋白的外源核酸序列。 该系统允许在病毒斑块筛选期间表达选择标记，而不是在靶蛋白产生时表达。

公开(公告)号：US06803361B2

公开(公告)日：2004-10-12

申请号：US10077489

申请日：2002-02-15

Applicant: Franciscus Antonius Maria Rijsewijk ,  Remco Siebren Schrijver ,  Johannes Theodorus Van Oirschot

Inventor： Franciscus Antonius Maria Rijsewijk ,  Remco Siebren Schrijver ,  Johannes Theodorus Van Oirschot

IPC: A61K4800

CPC classification number: A61K39/265 ,  A61K39/12 ,  A61K39/155 ,  A61K2039/5256 ,  A61K2039/54 ,  A61K2039/552 ,  C12N2710/16734 ,  C12N2710/16743 ,  C12N2760/18534 ,  C12N2760/18543

Abstract: Disclosed and claimed is the use of a liquid jet intradermal administration apparatus that administers a composition: without a needle; and in the epidermis, dermis and/or hypodermis, such as a Pigjet apparatus, for administering bovine vaccines or immunogenic compositions, especially bovine plasmid vaccines or immunogenic compositions. Accordingly, the invention involves bovine immunogenic or vaccine compositions in such an apparatus, and methods for vaccinating bovines or for inducing an immunogenic response in bovines employing such an apparatus, as well as the apparatus containing bovine immunogenic or vaccine compositions.

Abstract translation: 公开并要求保护的是使用无喷针施用组合物的液体喷射皮内给药装置; 以及表皮，真皮和/或皮下组织，例如Pigjet装置，用于施用牛疫苗或免疫原性组合物，特别是牛质粒疫苗或免疫原性组合物。 因此，本发明涉及这种装置中的牛免疫原性或疫苗组合物，以及使用这种装置的牛中疫苗接种或用于诱导免疫原性应答的方法，以及含有牛免疫原性或疫苗组合物的装置。

公开(公告)号：US06800281B2

公开(公告)日：2004-10-05

申请号：US10008610

申请日：2001-11-08

Applicant: Patrick Aebischer ,  Susan Mary Kingsman ,  Stuart Naylor ,  Nicholas Mazarakis

Inventor： Patrick Aebischer ,  Susan Mary Kingsman ,  Stuart Naylor ,  Nicholas Mazarakis

IPC: A61K4800

CPC classification number: C12N15/86 ,  A61K48/00 ,  C07K14/4756 ,  C12N2740/15043

Abstract: Disclosed and claimed are methods for treating or preventing neurodegenerative diseases, conditions or maladies or symptoms or physiology associated therewith, such as treating or preventing Parkinson's disease or symptoms or physiology associated therewith such as motor deficits or nigrostriatal degeneration; or, for inducing nigrostriatal regeneration. Advantageously, the methods involve administering a lentiviral vector that expresses GDNF, such as human GDNF, or a variant, homolog, analog or derivative thereof.

Abstract translation: 公开并要求保护的是用于治疗或预防神经变性疾病，病症或疾病或症状或与之相关的生理学的方法，例如治疗或预防帕金森病或与之相关的症状或生理学，例如运动缺陷或黑质纹状体变性; 或用于诱导黑质纹状体再生。 有利地，所述方法包括施用表达GDNF的慢病毒载体，例如人GDNF，或其变体，同系物，类似物或衍生物。

公开(公告)号：US06774119B1

公开(公告)日：2004-08-10

申请号：US09299817

申请日：1999-04-26

Applicant: Steven L. Wechsler ,  Anthony B. Nesburn ,  Guey-Chuen Perng ,  John S. Yu ,  Keith L. Black

Inventor： Steven L. Wechsler ,  Anthony B. Nesburn ,  Guey-Chuen Perng ,  John S. Yu ,  Keith L. Black

IPC: A61K4800

CPC classification number: C12N7/00 ,  A61K39/00 ,  A61K48/00 ,  C07K14/005 ,  C12N15/86 ,  C12N2710/16622 ,  C12N2710/16643 ,  C12N2710/16661

Abstract: Disclosed is a method of selectively inhibiting the growth of malignant cells in mammals, including humans. The method selectively inhibits the growth of malignant cells of all varieties, and is particularly useful in treating brain tumors and other malignancies of the central nervous system. The method employs HSV-1-derived vectors containing a DNA having a deletion in both copies of the LAT gene and both copies of the ICP34.5 gene of HSV-1. The vectors are delivered to malignant cells either in vivo or in vitro, in accordance with the method. The HSV-1-derived expression vectors are non-neurovirulent and do not spontaneously reactivate from latency, and they optionally contain a functional HSV thymidine kinase gene, which can enhance the effectiveness against cancer of drug treatment with gancyclovir or acyclovir. Alternatively, the HSV-1-derived vectors contain at least one transcriptional unit of a LAT promoter sequence operatively linked to a nucleic acid having a nucleotide sequence encoding a polypeptide toxic for cells expressing the vector, for example, human interferon-&ggr;. A method of expressing in a mammalian cell a gene encoding a preselected protein, a method of treating a genetic defect, and a method of detecting an HSV-1 expressing cell also employ vectors of the present invention that contain at least one transcriptional unit of a constitutive LAT promoter operatively linked to and controlling the transcription of a gene encoding a preselected protein. Also, disclosed are kits for expressing in a mammalian cell a gene encoding a preselected protein, useful for practicing the methods, and mammalian cells containing the HSV-derived vectors.

Abstract translation: 公开了一种选择性抑制包括人在内的哺乳动物中恶性细胞生长的方法。 该方法选择性地抑制所有品种的恶性细胞的生长，并且特别可用于治疗中枢神经系统的脑肿瘤和其他恶性肿瘤。 该方法使用含有两个拷贝的LAT基因和HSV-1的ICP34.5基因的两个拷贝的具有缺失的DNA的HSV-1衍生载体。 根据该方法，在体内或体外将载体递送至恶性细胞。 HSV-1衍生的表达载体是非神经毒性的，并且不会从潜伏期自发地再激活，并且它们任选地含有功能性HSV胸苷激酶基因，其可以增强用喷昔洛维或阿昔洛韦进行药物治疗的癌症的有效性。 或者，HSV-1衍生的载体含有至少一个LAT启动子序列的转录单位，该转录单位可操作地连接到具有编码对表达载体的细胞有毒的多肽的核苷酸序列的核酸，例如人类干扰素-γ。 在哺乳动物细胞中表达编码预选蛋白质的基因，治疗遗传缺陷的方法和检测表达HSV-1的细胞的方法的方法也采用本发明的载体，其含有至少一个转录单位 组成型LAT启动子与编码预选蛋白质的基因的转录有效连接并控制其转录。 此外，公开了用于在哺乳动物细胞中表达编码用于实施该方法的预选蛋白质的基因和含有HSV衍生载体的哺乳动物细胞的试剂盒。

公开(公告)号：US06737413B2

公开(公告)日：2004-05-18

申请号：US09910087

申请日：2001-07-20

Applicant: Peter Anthony Koopman ,  Peter Neville Goodfellow

Inventor： Peter Anthony Koopman ,  Peter Neville Goodfellow

IPC: A61K4800

CPC classification number: C07K14/4705 ,  A61K38/00 ,  A61K48/00

Abstract: This invention relates to an isolated DNA molecule encoding a Sox-9 gene which codes for the Sox-9 polypeptide. The human SOX-9 gene has been mapped to chromosome 17 in the same region as CMPD-1, the locus for Campomelic Dysplasia (CD). Sox-9 appears to have a role in mammalian skeletal development, and is used in the treatment of diseases involving bone or cartilage deficiency.

Abstract translation: 本发明涉及编码Sox-9多肽的Sox-9基因的分离的DNA分子。 人类SOX-9基因已被定位于与CMPD-1（Campomelic发育不良（CD））的相同区域的染色体17。 Sox-9似乎在哺乳动物骨骼发育中起作用，用于治疗涉及骨骼或软骨缺陷的疾病。

公开(公告)号：US06710037B2

公开(公告)日：2004-03-23

申请号：US10137057

申请日：2002-05-01

Applicant: Lynn Wang ,  Richard W. Bond ,  Jonathan A. Pachter

Inventor： Lynn Wang ,  Richard W. Bond ,  Jonathan A. Pachter

IPC: A61K4800

CPC classification number: C12N15/86 ,  A61K38/443 ,  A61K48/00 ,  C12N2710/10343 ,  A61K2300/00

Abstract: Novel methods of treating subjects afflicted with an androgen-dependent disorder, such as prostate cancer and benign prostatic hyperplasia are disclosed. Specifically, methods of treating androgen-dependent disorders by introducing a polypeptide or a polynucleotide encoding the polypeptide, which enhances inactivation of active androgens, are described.

Abstract translation: 公开了治疗患有雄激素依赖性疾病如前列腺癌和良性前列腺增生的受试者的新方法。 具体地，描述了通过引入增强活化雄激素失活的多肽或编码多肽的多核苷酸来治疗雄激素依赖性病症的方法。

公开(公告)号：US06710036B2

公开(公告)日：2004-03-23

申请号：US09858728

申请日：2001-05-16

Applicant: Gary J. Kurtzman ,  Edgar G. Engelman ,  Greg M. Podsakoff ,  Dirk G. Brockstedt

Inventor： Gary J. Kurtzman ,  Edgar G. Engelman ,  Greg M. Podsakoff ,  Dirk G. Brockstedt

IPC: A61K4800

CPC classification number: B60R21/01532 ,  B60N2/002 ,  B60R21/0152

Abstract: The present invention relates generally to immunization methods using recombinant viral vectors. In particular, the invention relates to methods and compositions for immunizing a subject with a nucleic acid molecule encoding an antigen of interest, wherein the nucleic acid molecule is delivered to the subject via a recombinant AAV virion.

Abstract translation: 本发明一般涉及使用重组病毒载体的免疫方法。 特别地，本发明涉及用编码感兴趣的抗原的核酸分子免疫受试者的方法和组合物，其中核酸分子通过重组AAV病毒粒子递送给受试者。

公开(公告)号：US06692738B2

公开(公告)日：2004-02-17

申请号：US09770339

申请日：2001-01-26

Applicant: David T. MacLaughlin ,  Joseph P. Vacanti ,  Patricia K. Donahoe ,  Peter T. Masiakos

Inventor： David T. MacLaughlin ,  Joseph P. Vacanti ,  Patricia K. Donahoe ,  Peter T. Masiakos

IPC: A61K4800

CPC classification number: C12N5/0656 ,  A61K38/22 ,  A61K48/00 ,  B33Y10/00 ,  B33Y30/00 ,  B33Y70/00 ,  B33Y80/00 ,  C12N2510/02

Abstract: Normal cells, such as fibroblasts or other tissue or organ cell types, are genetically engineered to express biologically active, therapeutic agents, such as proteins that are normally produced in small amounts, for example, MIS, or other members of the TGF-beta family Herceptin™, interferons, andanti-angiogenic factors. These cells are seeded into a matrix for implantation into the patient to be treated. Cells may also be engineered to include a lethal gene, so that implanted cells can be destroyed once treatment is completed. Cells can be implanted in a variety of different matrices. In a preferred embodiment, these matrices are implantable and biodegradable over a period of time equal to or less than the expected period of treatment, when cells engraft to form a functional tissue producing the desired biologically active agent. Implantation may be ectopic or in some cases orthotopic. Representative cell types include tissue specific cells, progenitor cells, and stem cells. Matrices can be formed of synthetic or natural materials, by chemical coupling at the time of implantation, using standard techniques for formation of fibrous matrices from polymeric fibers, and using micromachining or microfabrication techniques. These devices and strategies are used as delivery systems via standard or minimally invasive implantation techniques for any number of parenterally deliverable recombinant proteins, particularly those that are difficult to produce in large amounts and/or active forms using conventional methods of purification, for the treatment of a variety of conditions that produce abnormal growth, including treatment of malignant and benign neoplasias, vascular malformations (hemangiomas), inflammatory conditions, keloid formation, abdominal or plural adhesions, endometriosis, congenital or endocrine abnormalities, and other conditions that can produce abnormal growth such as infection. Efficacy of treatment with the therapeutic biologicals is detected by determining specific criteria, for example, cessation of cell proliferation, regression of abnormal tissue, or cell death, or expression of genes or proteins reflecting the above.