公开(公告)号：US06207804B1

公开(公告)日：2001-03-27

申请号：US08575724

申请日：1995-12-18

Applicant: James S. Huston ,  Hermann Oppermann

Inventor： James S. Huston ,  Hermann Oppermann

IPC: C12P2108

CPC classification number: C07K16/18 ,  C07K16/00 ,  C07K16/464 ,  C07K16/468 ,  C07K2317/24 ,  C07K2317/622 ,  C07K2317/624 ,  C07K2319/00 ,  C07K2319/02 ,  C07K2319/705

Abstract: Disclosed are a family of synthetic proteins having affinity for a preselected antigen. The proteins are characterized by one or more sequences of amino acids constituting a region which behaves as a biosynthetic antibody binding site (BABS). The sites comprise 1) non-covalently associated or disulfide bonded synthetic VH and VL dimers, 2) VH-VL or VL-VH single chains wherein the VH and VL are attached by a polypeptide linker, or 3) individual VH or VL domains. The binding domains comprise linked CDR and FR regions, which may be derived from separate immunoglobulins. The proteins may also include other polypeptide sequences which function e.g., as an enzyme, toxin, binding site, or site of attachment to an immobilization media or radioactive atom. Methods are disclosed for producing the proteins, for designing BABS having any specificity that can be elicited by in vivo generation of antibody, and for producing analogs thereof.

Abstract translation: 公开了对预选抗原具有亲和力的合成蛋白家族。 蛋白质的特征在于构成表现为生物合成抗体结合位点（BABS）的区域的一个或多个氨基酸序列。 所述位点包括1）非共价缔合或二硫键合的合成的VH和VL二聚体，2）其中VH和VL通过多肽接头连接的VH-VL或VL-VH单链，或3）个体VH或VL结构域。 结合域包含连接的CDR和FR区，其可以衍生自单独的免疫球蛋白。 蛋白质还可以包括其它多肽序列，其例如作为酶，毒素，结合位点或与固定化介质或放射性原子的连接位点起作用。 公开了用于生产蛋白质的方法，用于设计具有可通过体内产生抗体引发的任何特异性的BABS和用于制备其类似物的方法。

公开(公告)号：US6093547A

公开(公告)日：2000-07-25

申请号：US459951

申请日：1995-06-02

Applicant: Donald F. Jin ,  Hermann Oppermann ,  Thangavel Kuberasampath ,  John E. Smart

Inventor： Donald F. Jin ,  Hermann Oppermann ,  Thangavel Kuberasampath ,  John E. Smart

IPC: C07K14/705 ,  G01N33/53 ,  G01N33/567

CPC classification number: C07K14/705 ,  Y10S435/81 ,  Y10S435/975

Abstract: Disclosed are (1) nucleic acid sequences, amino acid sequences, homologies, structural features and various other data characterizing a morphogen cell surface receptor; (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 for identifying compounds capable of modulating endogenous morphogen receptor levels; and (5) methods for identifying morphogen receptor binding analogs useful in the design of morphogen agonists and antagonists for therapeutic, diagnostic and experimental uses.

Abstract translation: 公开了（1）表征形态发生细胞表面受体的核酸序列，氨基酸序列，同源性，结构特征和各种其他数据; （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; 以及（5）用于鉴定形态发生受体结合类似物的方法，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：US6077823A

公开(公告)日：2000-06-20

申请号：US445467

申请日：1995-05-22

Applicant: Thangavel Kuberasampath ,  Roy H. L. Pang ,  Hermann Oppermann ,  David C. Rueger ,  Charles M. Cohen ,  John E. Smart

Inventor： Thangavel Kuberasampath ,  Roy H. L. Pang ,  Hermann Oppermann ,  David C. Rueger ,  Charles M. Cohen ,  John E. Smart

IPC: A01N1/02 ,  A61F2/00 ,  A61K6/00 ,  A61K38/17 ,  A61K38/18 ,  A61L27/22 ,  A61L27/24 ,  C07K14/495 ,  C07K14/51 ,  C07K16/22

CPC classification number: A61K38/17 ,  A01N1/0226 ,  A61K38/1703 ,  A61K38/1875 ,  A61L27/227 ,  A61L27/24 ,  C07K14/495 ,  C07K14/51 ,  C07K16/22 ,  A61F2310/00365 ,  G01N2500/10

Abstract: The present invention is directed to methods and compositions for alleviating tissue destructive effects associated with the inflammatory response to tissue injury in a mammal. The methods and compositions include administering a therapeutically effective concentration of a morphogen or morphogen-stimulating agent sufficient to alleviate immune cell-mediated tissue destruction.

Abstract translation: 本发明涉及减轻与哺乳动物对组织损伤的炎症反应相关的组织破坏作用的方法和组合物。 所述方法和组合物包括施用足以减轻免疫细胞介导的组织破坏的治疗有效浓度的形态发生剂或形态发生剂。

公开(公告)号：US6071695A

公开(公告)日：2000-06-06

申请号：US486343

申请日：1995-06-07

Applicant: Engin Ozkaynak ,  Hermann Oppermann

Inventor： Engin Ozkaynak ,  Hermann Oppermann

IPC: C07K14/51 ,  C12Q1/68 ,  C12N5/10 ,  C12N15/85 ,  C12Q1/02

CPC classification number: C07K14/51 ,  A61L2430/02

Abstract: Disclosed are methods and compositions for screening compounds for their ability to modulate expression of a tissue morphogenetic protein, particularly OP-1, OP-1 homologs and closely related proteins, using one or more OP-1-specific, noncoding nucleotide sequences and a suitable reporter gene.

Abstract translation: 公开了使用一种或多种OP-1特异性，非编码核苷酸序列和适合的方法来筛选化合物调节组织形态发生蛋白，特别是OP-1，OP-1同源物和密切相关蛋白的表达的能力的方法和组合物 记者基因。

公开(公告)号：US5972884A

公开(公告)日：1999-10-26

申请号：US461397

申请日：1995-06-05

Applicant: Charles M. Cohen ,  Marc F. Charette ,  Thangavel Kuberasampath ,  David C. Rueger ,  Hermann Oppermann ,  Roy H. L. Pang

Inventor： Charles M. Cohen ,  Marc F. Charette ,  Thangavel Kuberasampath ,  David C. Rueger ,  Hermann Oppermann ,  Roy H. L. Pang

IPC: A01N1/02 ,  A61F2/00 ,  A61K6/00 ,  A61K38/00 ,  A61K38/18 ,  A61L27/22 ,  A61L27/24 ,  C07K14/51 ,  C07K16/22

CPC classification number: C07K16/22 ,  A61K38/1875 ,  A61L27/227 ,  A61L27/24 ,  C07K14/51 ,  A61F2310/00365 ,  G01N2500/10 ,  G01N2800/06

Abstract: Disclosed are methods and compositions for maintaining the integrity of the gastrointestinal tract luminal lining in a mammal, including (1) limiting epithelial cell proliferation, (2) inhibiting ulcerative lesion formation, (3) inhibiting inflammation normally associated with ulcerative diseases, and (4) stimulating the repair of ulcerative lesions and the regeneration of the luminal tissue. The methods and compositions include a therapeutically effective amount of a morphogen as defined herein.

Abstract translation: 公开了用于维持哺乳动物胃肠道腔内衬的完整性的方法和组合物，包括（1）限制上皮细胞增殖，（2）抑制溃疡性病变形成，（3）抑制通常与溃疡性疾病相关的炎症，和（4 ）刺激溃疡性病变的修复和管腔组织的再生。 方法和组合物包括治疗有效量的如本文所定义的形态发生素。

公开(公告)号：US5958441A

公开(公告)日：1999-09-28

申请号：US449699

申请日：1995-05-24

Applicant: Hermann Oppermann ,  Engin Ozkaynak ,  Thangavel Kuberasampath ,  David C. Rueger ,  Roy H. L. Pang

Inventor： Hermann Oppermann ,  Engin Ozkaynak ,  Thangavel Kuberasampath ,  David C. Rueger ,  Roy H. L. Pang

IPC: A61C8/00 ,  A61F2/00 ,  A61K6/00 ,  A61K9/00 ,  A61K38/00 ,  A61K38/18 ,  A61L27/22 ,  A61L27/24 ,  A61L27/34 ,  A61L27/36 ,  A61L27/56 ,  C04B14/12 ,  C04B20/06 ,  C07K14/51

CPC classification number: A61K9/0024 ,  A61K38/1875 ,  A61L27/227 ,  A61L27/24 ,  A61L27/34 ,  A61L27/3604 ,  A61L27/3608 ,  A61L27/365 ,  A61L27/3654 ,  A61L27/3683 ,  A61L27/54 ,  A61L27/56 ,  C04B14/12 ,  C04B20/068 ,  C07K14/51 ,  A61C8/0006 ,  A61F2310/00365 ,  A61L2300/412 ,  A61L2430/02 ,  Y10S530/84

Abstract: Disclosed are (1) osteogenic devices comprising a matrix containing substantially pure natural-sourced mammalian osteogenic protein; (2) DNA and amino acid sequences for novel polypeptide chains useful as subunits of dimeric osteogenic proteins; (3) vectors carrying sequences encoding these novel polypeptide chains and host cells transfected with these vectors; (4) methods of producing these polypeptide chains using recombinant DNA technology; (5) antibodies specific for these novel polypeptide chains; (6) osteogenic devices comprising these recombinantly produced proteins in association with an appropriate carrier matrix; and (7) methods of using the osteogenic devices to mimic the natural course of endochondral bone formation in mammals.

Abstract translation: 公开的是（1）包含含有基本上纯天然来源的哺乳动物成骨蛋白质的基质的成骨装置; （2）可用作二聚成骨蛋白亚基的新型多肽链的DNA和氨基酸序列; （3）携带编码这些新型多肽链的序列的载体和用这些载体转染的宿主细胞; （4）使用重组DNA技术生产这些多肽链的方法; （5）对这些新型多肽链具有特异性的抗体; （6）包含这些重组产生的蛋白质与合适的载体基质相结合的成骨装置; 和（7）使用成骨装置来模拟哺乳动物软骨内骨形成的自然过程的方法。

公开(公告)号：US5854071A

公开(公告)日：1998-12-29

申请号：US901200

申请日：1997-07-28

Applicant: Hermann Oppermann ,  Engin Ozkaynak ,  Thangavel Kuberasampath ,  David C. Rueger ,  Roy H. L. Pang ,  Charles M. Cohen

Inventor： Hermann Oppermann ,  Engin Ozkaynak ,  Thangavel Kuberasampath ,  David C. Rueger ,  Roy H. L. Pang ,  Charles M. Cohen

IPC: A01N1/02 ,  A61F2/00 ,  A61K6/00 ,  A61K38/00 ,  A61L27/22 ,  A61L27/24 ,  C07K14/51 ,  C07K14/625 ,  C07K16/22 ,  C12Q1/68 ,  C12N5/06 ,  C07K14/00 ,  C12N5/08

CPC classification number: C12Q1/6881 ,  A01N1/02 ,  A61L27/227 ,  A61L27/24 ,  C07K14/51 ,  C07K14/625 ,  C07K16/22 ,  A61F2310/00365 ,  A61K38/00 ,  C12Q2600/156 ,  C12Q2600/158 ,  G01N2500/10

Abstract: Disclosed are (1) nucleic acid and amino acid sequences for a novel morphogenic protein; (2) methods for producing and expressing the protein in a biologically active form; and (3) methods for utilizing the protein to induce tissue morphogenesis in a mammal, including methods for increasing a progenitor cell population in a mammal, methods for stimulating progenitor cells to differentiate and maintain their differentiated phenotype in vivo or in vitro, methods for inducing tissue-specific growth in vivo and methods for the replacement of diseased or damaged tissue in vivo.

Abstract translation: 公开了（1）新型形态发生蛋白的核酸和氨基酸序列; （2）以生物活性形式生产和表达蛋白质的方法; 和（3）利用蛋白质诱导哺乳动物组织形态发生的方法，包括增加哺乳动物祖细胞群的方法，用于刺激祖细胞在体内或体外分化和维持其分化表型的方法，诱导方法 体内的组织特异性生长和体内替换患病或受损组织的方法。

公开(公告)号：US5849686A

公开(公告)日：1998-12-15

申请号：US445468

申请日：1995-05-22

Applicant: Thangavel Kuberasampath ,  David C. Rueger ,  Hermann Oppermann ,  Roy H. L. Pang ,  Charles M. Cohen

Inventor： Thangavel Kuberasampath ,  David C. Rueger ,  Hermann Oppermann ,  Roy H. L. Pang ,  Charles M. Cohen

IPC: A01N1/02 ,  A61F2/00 ,  A61K6/00 ,  A61K38/00 ,  A61K38/18 ,  A61L27/22 ,  A61L27/24 ,  A61P1/16 ,  C07K14/51 ,  C07K16/22 ,  A61K38/17

CPC classification number: C07K16/22 ,  A01N1/0226 ,  A61K38/1875 ,  A61L27/227 ,  A61L27/24 ,  C07K14/51 ,  A61F2310/00365 ,  G01N2500/10

Abstract: Disclosed are therapeutic treatment methods, compositions and devices for maintaining liver function in a mammal, including methods, compositions and devices for regenerating lost or damaged hepatic tisse, enhancing viability and integration of hepatic tissue and organ transplants, and correcting liver function deficiencies. The methods, compositions and devices on this invention all provide a therapeutically effective morphogen concentration to the hepatic cells to be treated.

Abstract translation: 本发明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方法，组合物和装置，增强肝组织和器官移植的活力和整合以及纠正肝功能缺陷。 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。

公开(公告)号：US5831050A

公开(公告)日：1998-11-03

申请号：US357533

申请日：1994-12-16

Applicant: Donald F. Jin ,  Hermann Oppermann ,  Thangavel Kuberasampath ,  John E. Smart

Inventor： Donald F. Jin ,  Hermann Oppermann ,  Thangavel Kuberasampath ,  John E. Smart

IPC: C07K14/705 ,  C07H21/04

CPC classification number: C07K14/705 ,  Y10S435/81 ,  Y10S435/975

Abstract: Disclosed are (1) nucleic acid sequences, amino acid sequences, homologies, structural features and various other data characterizing a morphogen cell surface receptor; (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 for identifying compounds capable of modulating endogenous morphogen receptor levels; and (5) methods for identifying morphogen receptor binding analogs useful in the design of morphogen agonists and antagonists for therapeutic, diagnostic and experimental uses.

公开(公告)号：US5814604A

公开(公告)日：1998-09-29

申请号：US417071

申请日：1995-04-04

Applicant: Hermann Oppermann ,  Thangavel Kuberasampath ,  David C. Rueger ,  Engin Ozkaynak

Inventor： Hermann Oppermann ,  Thangavel Kuberasampath ,  David C. Rueger ,  Engin Ozkaynak

IPC: C12N15/02 ,  A61C8/00 ,  A61F2/00 ,  A61K9/00 ,  A61K38/00 ,  A61K39/395 ,  A61L27/00 ,  A61L27/22 ,  A61L27/24 ,  A61L27/34 ,  A61L27/36 ,  A61L27/56 ,  A61P1/02 ,  A61P43/00 ,  C07H21/04 ,  C07K1/20 ,  C07K1/22 ,  C07K7/06 ,  C07K7/08 ,  C07K14/00 ,  C07K14/51 ,  C07K14/78 ,  C07K16/00 ,  C12N1/19 ,  C12N1/21 ,  C12N5/10 ,  C12N15/09 ,  C12N15/12 ,  C12N15/18 ,  C12P21/02 ,  C12P21/08 ,  C12Q1/68 ,  C12R1/07 ,  C12R1/19 ,  C12R1/645 ,  C12R1/91 ,  A61K38/16

CPC classification number: A61K9/0024 ,  A61L27/227 ,  A61L27/24 ,  A61L27/34 ,  A61L27/3604 ,  A61L27/3608 ,  A61L27/365 ,  A61L27/3654 ,  A61L27/56 ,  C07K14/51 ,  A61C8/0006 ,  A61F2310/00365 ,  A61K38/00 ,  A61L2430/02

Abstract: Disclosed are 1) osteogenic devices comprising a matrix containing osteogenic protein and methods of inducing endochondral bone growth in mammals using the devices; 2) amino acid sequence data, amino acid composition, solubility properties, structural features, homologies and various other data characterizing osteogenic proteins, 3) methods of producing osteogenic proteins using recombinant DNA technology, and 4) osteogenically and chondrogenically active synthetic protein constructs.

Abstract translation: 公开的是1）包含含有成骨蛋白的基质的成骨装置和使用该装置在哺乳动物中诱导软骨内骨生长的方法; 2）氨基酸序列数据，氨基酸组成，溶解性，结构特征，同源性和各种其他数据表征成骨蛋白，3）使用重组DNA技术生产成骨蛋白的方法，以及4）成骨和软骨形成活性合成蛋白质构建体。