公开(公告)号：WO1998020890A1

公开(公告)日：1998-05-22

申请号：PCT/US1997020743

申请日：1997-11-14

Applicant: CREATIVE BIOMOLECULES, INC.

Inventor： CREATIVE BIOMOLECULES, INC. ,  SAMPATH, Kuber ,  RUEGER, David, C. ,  COHEN, Charles, M. ,  CHARETTE, Marc, F. ,  JIN, Donald, F.

IPC: A61K38/18

CPC classification number: A61K38/1875

Abstract: Disclosed are methods and compositions for the treatment and prophylaxis of sensory perception deficits. Methods involve the administration of certain morphogenic compositions.

Abstract translation: 公开了用于治疗和预防感觉知觉缺陷的方法和组合物。 方法涉及给予某些形态发生组合物。

公开(公告)号：WO1995030003A2

公开(公告)日：1995-11-09

申请号：PCT/US1995005467

申请日：1995-04-28

Applicant: CREATIVE BIOMOLECULES, INC. ,  THE LUDWIG INSTITUTE FOR CANCER RESEARCH ,  DIJKE, Peter, T. ,  MIYAZANO, Kohei ,  SAMPATH, Kuber, T. ,  HELDIN, Carl-Henrik

Inventor： CREATIVE BIOMOLECULES, INC. ,  THE LUDWIG INSTITUTE FOR CANCER RESEARCH

IPC: C12N15/12

CPC classification number: G01N33/6845 ,  A61K38/00 ,  C07K14/51 ,  C07K14/71 ,  G01N33/566 ,  G01N33/567 ,  G01N33/68 ,  G01N33/6887 ,  G01N33/74 ,  G01N2500/00 ,  G01N2500/04

Abstract: Disclosed are: (1) nucleic acid sequences, amino acid sequences, homologies, structural features and various other data characterizing a morphogen cell surface receptors particularly OP-1-binding cell surface receptors; (2) methods for producing receptor proteins, including fragments thereof, using recombinant DNA technology; (3) methods for identifying novel morphogen receptors and their encoding DNAs; (4) methods and compositions for identifying compounds capable of modulating endogenous morphogen receptor levels; and (5) methods and compositions for identifying morphogen receptor binding analogs useful in the design of morphogen agonists and antagonists for therapeutic, diagnostic and experimental uses.

Abstract translation: 公开的是：（1）核酸序列，氨基酸序列，同源性，结构特征以及表征形态发生细胞表面受体，特别是OP-1结合细胞表面受体的各种其它数据; （2）使用重组DNA技术生产受体蛋白，包括其片段的方法; （3）鉴定新型形态发生受体及其编码DNA的方法; （4）鉴定能够调节内源性形态发生物受体水平的化合物的方法和组合物; 和（5）用于鉴定形态发生受体结合类似物的方法和组合物，其可用于设计用于治疗，诊断和实验用途的形态发生激动剂和拮抗剂。

公开(公告)号：WO1994006449A2

公开(公告)日：1994-03-31

申请号：PCT/US1993008808

申请日：1993-09-16

Applicant: CREATIVE BIOMOLECULES, INC.

Inventor： CREATIVE BIOMOLECULES, INC. ,  KUBERASAMPATH, Thangavel ,  RUEGER, David, C. ,  OPPERMANN, Hermann ,  PANG, Roy, H., L. ,  COHEN, Charles, M. ,  OZKAYNAK, Engin ,  SMART, John, E.

IPC: A61K37/00

CPC classification number: A61K38/1875 ,  A61F2310/00365 ,  A61K48/00 ,  A61L27/227 ,  A61L27/24 ,  C07K14/51 ,  C07K16/22

Abstract: Disclosed are therapeutic treatment methods, compositions and devices for maintaining liver function in a mammal, including means for regenerating lost or damaged hepatic tissue, means for enhancing viability and integration of hepatic tissue and organ transplants, and means for correcting liver function deficiencies, including means for enhancing diminished liver function due to tissue injury or disease. The methods, compositions and devices on this invention all provide a therapeutically effective morphogen concentration to the hepatic cells to be treated. Also disclosed are methods and compositions useful in a gene therapy or drug delivery protocol for correcting a protein deficiency in a mammal.

Abstract translation: 公开了用于维持哺乳动物肝功能的治疗方法，组合物和装置，包括用于再生损伤或损伤的肝组织的手段，用于增强肝组织和器官移植的活力和整合的手段，以及用于矫正肝功能缺陷的手段，包括手段 用于增强由于组织损伤或疾病引起的肝功能减退。 本发明的方法，组合物和装置都提供对待治疗的肝细胞的治疗有效的形态发生浓度。 还公开了可用于校正哺乳动物蛋白质缺乏症的基因治疗或药物递送方案中的方法和组合物。

公开(公告)号：WO1994003200A1

公开(公告)日：1994-02-17

申请号：PCT/US1993007231

申请日：1993-07-29

Applicant: CREATIVE BIOMOLECULES, INC.

Inventor： CREATIVE BIOMOLECULES, INC. ,  RUEGER, David, C. ,  KUBERASAMPATH, Thangavel ,  OPPERMANN, Hermann ,  OZKAYNAK, Engin ,  PANG, Roy, H., L. ,  COHEN, Charles, M.

IPC: A61K37/02

CPC classification number: C07K16/22 ,  A61F2310/00365 ,  A61K38/1875 ,  A61K48/00 ,  A61L27/227 ,  A61L27/24 ,  A61L2430/32 ,  C07K14/51

Abstract: Disclosed are therapeutic treatment methods, compositions and devices for maintaining neural pathways in a mammal, including enhancing survival of neurons at risk of dying, inducing cellular repair of damaged neurons and neural pathways, and stimulating neurons to maintain their differentiated phenotype. In one embodiment, the invention provides means for stimulating CAM expression in neurons. The invention also provides means for evaluating the status of nerve tissue, including means for detecting and monitoring neuropathies in a mammal. The methods, devices and compositions include a morphogen-stimulating agent provided to the mammal in a therapeutically effective concentration.

Abstract translation: 公开了用于在哺乳动物中维持神经通路的治疗治疗方法，组合物和装置，包括增加有死亡风险的神经元的存活，诱导受损神经元和神经通路的细胞修复，以及刺激神经元维持其分化表型。 在一个实施方案中，本发明提供用于刺激神经元中的CAM表达的装置。 本发明还提供了用于评估神经组织状态的手段，包括用于检测和监测哺乳动物神经病变的手段。 方法，装置和组合物包括以治疗有效浓度提供给哺乳动物的形态发生剂刺激剂。

公开(公告)号：WO1992010567A1

公开(公告)日：1992-06-25

申请号：PCT/US1991009275

申请日：1991-12-10

Applicant: CREATIVE BIOMOLECULES, INC.

Inventor： CREATIVE BIOMOLECULES, INC. ,  PANG, Roy, H., L. ,  COHEN, Charles, M. ,  KECK, Peter, C.

IPC: C12N15/11

CPC classification number: C07K14/001 ,  A61L24/106 ,  A61L27/227

Abstract: This invention pertains to a synthetic adhesive composition for use in aqueous environments. The composition comprises polypeptide chains having an α-helical structure in aqueous environments and capable of cohesive and adhesive interactions. The polypeptide chains comprise polar and apolar amino acids, the apolar and polar amino acids being arranged to define apolar and polar vertical spiraling stripes on the helix surface. The apolar strips allow the polypeptide chains to aggregate into superhelical structures and the polar stripes allow interchain crosslinking within and between the superhelical structures.

公开(公告)号：WO1991005565A1

公开(公告)日：1991-05-02

申请号：PCT/US1990006006

申请日：1990-10-18

Applicant: CREATIVE BIOMOLECULES, INC.

Inventor： CREATIVE BIOMOLECULES, INC. ,  COHEN, Charles, M.

IPC: A61K37/24

CPC classification number: C07K14/495 ,  A61K38/00

Abstract: Disclosed are constructs of truncated transforming growth factor-beta (TGF- beta ) produced by expression of recombinant DNA in a prokaryotic host cell. These constructs include at least one polypeptide chain of fewer than about 112 amino acides and fewer than 9 cysteine residues. The sequence of amino acids in these constructs is sufficiently duplicative of the sequence of native transforming growth factor-beta such that it is capable of inducing an anti-proliferative effect on mammalian epithelial cells in vitro. Also disclosed are methods of producing analogs of TGF- beta using recombinant DNA technology, and methods of using such analogs.

Abstract translation: 公开了通过在原核宿主细胞中表达重组DNA产生的截短的转化生长因子-β（TGF-β）的构建体。 这些构建体包括至少一个少于约112个氨基酸和少于9个半胱氨酸残基的多肽链。 这些构建体中的氨基酸序列与天然转化生长因子-β的序列充分重复，使得其能够在体外诱导哺乳动物上皮细胞的抗增殖作用。 还公开了使用重组DNA技术生产TGF-β类似物的方法，以及使用这些类似物的方法。

公开(公告)号：WO1989004675A1

公开(公告)日：1989-06-01

申请号：PCT/US1988003611

申请日：1988-10-17

Applicant: CREATIVE BIOMOLECULES, INC.

Inventor： CREATIVE BIOMOLECULES, INC. ,  HUSTON, James, S. ,  BAIRD, Lynn ,  COHEN, Charles ,  OPPERMAN, Hermann

IPC: A61M01/36

CPC classification number: A61M1/3679 ,  C07K14/31 ,  C07K17/06

Abstract: Disclosed is a method and a family of materials useful for removing immune complexes from blood preferentially to soluble antibodies. The material comprises analogs of proteins which bind to the Fc region of immunoglobulin. The analogs are produced by truncating or otherwise altering the amino acid sequence of the binding protein to reduce their affinity for Fc. An array of such analogs disposed about the surface of an insoluble matrix has the ability to form multiple points of attachment to the multiple Fc's in a complex so as to bind complex strongly, whereas only weak associations are developed between the Fc region of soluble IgG and individual analogs. The preferred analogs are truncated proteins homologous to a portion of the domains of Protein A or Protein G which bind with Fc. Complex may be removed from whole blood or serum using the material and conventional plasmapheresis techniques.

Abstract translation: 公开了一种用于从血液中将免疫复合物优先地去除可溶性抗体的方法和一系列材料。 该材料包含与免疫球蛋白Fc区结合的蛋白质的类似物。 通过截短或以其他方式改变结合蛋白的氨基酸序列来降低它们对Fc的亲和力来产生类似物。 在不溶性基质的表面附近设置的这种类似物的阵列具有在复合物中形成与多个Fc的多个连接点的能力，以便强烈地结合复合物，而仅在可溶性IgG的Fc区和 个别类似物。 优选的类似物是与蛋白A或蛋白G的结合部分与Fc结合的截短的蛋白质。 可以使用材料和常规的血浆置换技术从全血或血清中除去复合物。

公开(公告)号：WO1988007085A1

公开(公告)日：1988-09-22

申请号：PCT/US1988000717

申请日：1988-03-04

Applicant: CREATIVE BIOMOLECULES, INC.

Inventor： CREATIVE BIOMOLECULES, INC. ,  HUSTON, James, S. ,  COHEN, Charles, M. ,  KECK, Peter, C. ,  RUEGER, David, C. ,  CHARETTE, Marc, F. ,  CREA, Roberto ,  OPPERMANN, Hermann ,  RIDGE, Richard, J.

IPC: C12N15/00

CPC classification number: C12N15/62 ,  C07K14/485 ,  C07K14/585 ,  C07K2319/00 ,  C07K2319/02 ,  C07K2319/036 ,  C07K2319/50 ,  C07K2319/75

Abstract: Disclosed is a method for the isolation and purification of polypeptides expressed in host cells by recombinant DNA techniques. A fused polypeptide is produced containing a desired polypeptide fused to additional amino acids. The additional amino acids define a leader sequence having properties exploitable in purification, a hinge region, and a cleavage site. The hinge region is cysteine-free and has a secondary structure which serves to expose the cleavage site to a selected endopeptidase. The method of the invention involves the production of a fused polypeptide which may be efficiently isolated by exploiting the properties of the leader sequence, and then efficiently cleaved at the cleavage site in an appropriate aqueous environment by virtue of the influence of the hinge on the cleavage agent/cleavage site reaction and other properties of the fused polypeptide.

Abstract translation: 公开了通过重组DNA技术分离和纯化在宿主细胞中表达的多肽的方法。 产生融合的多肽，其含有与另外的氨基酸融合的所需多肽。 另外的氨基酸定义具有在纯化中可利用的性质，铰链区和切割位点的前导序列。 铰链区域是无半胱氨酸的并且具有用于将切割位点暴露于所选择的内肽酶的二级结构。 本发明的方法涉及产生融合多肽，其可以通过利用前导序列的性质而有效分离，然后由于铰链对切割的影响，在合适的水性环境中的切割位点处有效地切割 试剂/裂解位点反应和融合多肽的其他性质。

公开(公告)号：WO1997034626A1

公开(公告)日：1997-09-25

申请号：PCT/US1997004177

申请日：1997-03-21

Applicant: CREATIVE BIOMOLECULES, INC. ,  THE GENERAL HOSPITAL CORPORATION

Inventor： CREATIVE BIOMOLECULES, INC. ,  THE GENERAL HOSPITAL CORPORATION ,  CHARETTE, Marc, F. ,  FINKLESTEIN, Seth, P.

IPC: A61K38/18

CPC classification number: A61K38/1875

Abstract: The present invention provides methods and compositions for treatment of mammals afflicted with an ischemic or traumatic injury of the central nervous system. The present invention capitalizes in part upon the discovery that administration of a morphogen to such a mammal provides significant improvement in central nervous system function, even when administered after central nervous system tissue has been damaged. The methods involve the administration of dimeric proteins defined as morphogens, inducers of these morphogens, or agonists of the corresponding morphogen receptors, or implantation of cells stimulated by exposure to the morphogens. The proteins defined as morphogens comprise a structurally and functionally distinct family within the TGF-β superfamily. Osteogenic protein-1 (OP-1) is considered to be an exemplary and preferred member of this morphogen family.

公开(公告)号：WO1997005241A2

公开(公告)日：1997-02-13

申请号：PCT/US1996012054

申请日：1996-07-22

Applicant: CREATIVE BIOMOLECULES, INC.

Inventor： CREATIVE BIOMOLECULES, INC. ,  SAMPATH, Kuber, T.

IPC: C12N05/16

CPC classification number: C07K14/51 ,  A61K38/00 ,  C12Q1/6897

Abstract: Disclosed herein are methods and compositions for identifying morphogen analogs. Preferred methods rest on the use of test cells comprising DNA defining a morphogen-responsive transcription activating element operatively associated with a reporter gene. In certain embodiments, the methods involve an osteogenic protein 1 (OP-1) responsive transcription activating element. Substances that activate the OP-1 responsive transcription activating element are considered herein likely to be useful for reproducing in vivo effects of morphogens such as OP-1.

Abstract translation: 本文公开了用于鉴定形态发生类似物的方法和组合物。 优选的方法在于使用测试细胞，所述测试细胞包含限定与报告基因操作相关的形态发生反应性转录激活元件的DNA。 在某些实施方案中，所述方法涉及成骨蛋白1（OP-1）响应转录激活元件。 本文认为激活OP-1反应性转录激活元件的物质可能用于再现诸如OP-1的形态发生体的作用。