公开(公告)号：US20010034327A1

公开(公告)日：2001-10-25

申请号：US09836323

申请日：2001-04-18

Inventor： Niels Brunner ,  John Romer ,  Vincent Ellis ,  Charles Pyke ,  Jan Grondahl-Hansen ,  Helle Pedersen Pappot ,  Heine Hoi Hansen ,  Keld Dano

IPC: G01N033/574 ,  A61K038/55

CPC classification number: G01N33/573 ,  A61K38/49 ,  A61K38/57 ,  A61K48/00 ,  C07K16/38 ,  G01N33/574 ,  G01N2333/47 ,  G01N2333/4704 ,  G01N2333/81

Abstract: The present invention relates to methods for inhibiting malignant tumour growth, invasion and/or metastasis in a patient, the method comprising suppressing the inhibitory activity of an inhibitor of a protease or of a non-proteolytic matrix-degrading enzyme (IPNME) in malignant tumour tissue or potential malignant tumour tissue. The suppression may be brought about by administering compounds interacting with the IPNME, but also administration of compounds interacting with transcription of genes encoding the IPNME is a possibility. The invention also relates to methods of selecting and identifying compounds in the therapeutical methods, as well of the use of such compounds in the treatment of malignancies.

Abstract translation: 本发明涉及抑制患者恶性肿瘤生长，侵袭和/或转移的方法，所述方法包括抑制蛋白酶抑制剂或非蛋白水解基质降解酶（IPNME）在恶性肿瘤中的抑制活性 组织或潜在的恶性肿瘤组织。 抑制可能是通过施用与IPNME相互作用的化合物引起的，但也可能与编码IPNME的基因的转录相互作用的化合物的施用是可能的。 本发明还涉及在治疗方法中选择和鉴定化合物的方法，以及这些化合物在恶性肿瘤治疗中的应用。

公开(公告)号：US06171587B2

公开(公告)日：2001-01-09

申请号：US09054782

申请日：1998-04-03

Applicant: Tze Chein Wun ,  Kuniko K. Kretzmer ,  George J. Broze, Jr.

Inventor： Tze Chein Wun ,  Kuniko K. Kretzmer ,  George J. Broze, Jr.

IPC: C07K1624

CPC classification number: C07K16/38 ,  A61K38/00 ,  A61K2039/505 ,  C07K14/8114

Abstract: A cDNA clone having a base sequence for human tissue factor inhibitor (TFI) has been developed and characterized and the amino acid sequence of the TFI has been determined. Antibodies having a binding region specific to human tissue factor inhibitor are disclosed.

Abstract translation: 已经开发并表征了具有人组织因子抑制剂（TFI）碱基序列的cDNA克隆，并且已经确定了TFI的氨基酸序列。 公开了具有对人组织因子抑制剂特异性结合区的抗体。

公开(公告)号：US6114506A

公开(公告)日：2000-09-05

申请号：US933983

申请日：1997-09-19

Applicant: Guy L. Reed ,  Linda Harris ,  Jurgen Bajorath ,  Gary Matsueda ,  Mei-Yin Hsu ,  Jiri Novotny

Inventor： Guy L. Reed ,  Linda Harris ,  Jurgen Bajorath ,  Gary Matsueda ,  Mei-Yin Hsu ,  Jiri Novotny

IPC: G01N33/53 ,  A61K38/00 ,  A61K39/395 ,  A61K45/00 ,  A61P7/02 ,  A61P9/10 ,  A61P11/00 ,  C07K16/18 ,  C07K16/38 ,  C07K16/46 ,  C12N5/10 ,  C12N15/09 ,  C12N15/13 ,  C12P21/08 ,  C12R1/91 ,  G01N33/86 ,  C07K16/00

CPC classification number: G01N33/86 ,  A61K39/395 ,  A61K39/3955 ,  C07K16/38 ,  A61K2039/505 ,  A61K38/00 ,  C07K2317/24 ,  C07K2319/00

Abstract: The present invention relates to a novel alpha-2-antiplasmin-binding molecules and treatment for pulmonary embolism, myocardial infarction, thrombosis or stroke in a patient which comprises administering an alpha-2-antiplasmin-binding molecule capable of preventing inhibition of plasmin by endogenous alpha-2-antiplasmin. The invention also relates to a treatment for pulmonary embolism, myocardial infarction, thrombosis or stroke in a patient comprising coadministrating an alpha-2-antiplasmin-binding molecule of the invention together with a thrombolytic agent.

公开(公告)号：US5914392A

公开(公告)日：1999-06-22

申请号：US111070

申请日：1998-07-07

Applicant: Phillip R. Hawkins ,  Lynn E. Murry

Inventor： Phillip R. Hawkins ,  Lynn E. Murry

IPC: A61K38/00 ,  C07K14/81 ,  C07K16/38 ,  C07K16/00 ,  A61K39/395

CPC classification number: C07K16/38 ,  C07K14/8146 ,  A61K38/00

Abstract: The present invention provides a nucleic acid sequence which identifies and encodes a novel tissue inhibitor of metalloproteinases (TIMP-4) which was isolated from cells of human uterus. The invention provides for TIMP-4 antisense molecules and genetically engineered expression vectors and host cells comprising nucleic acid sequence encoding TIMP-4. The invention also provides for purified TIMP-4; antibodies, antagonists and inhibitors which specifically bind TIMP-4; and pharmaceutical compositions and methods of treatment based on TIMP-4, its antagonists and inhibitors. The invention provides for diagnostic assays which utilize diagnostic compositions comprising nucleic acid sequences encoding to TIMP-4, or complements thereof, and antibodies which specifically bind to TIMP-4.

Abstract translation: 本发明提供了鉴定和编码从人子宫细胞分离的金属蛋白酶（TIMP-4）的新型组织抑制剂的核酸序列。 本发明提供TIMP-4反义分子和遗传工程改造的表达载体以及包含编码TIMP-4的核酸序列的宿主细胞。 本发明还提供了纯化的TIMP-4; 特异性结合TIMP-4的抗体，拮抗剂和抑制剂; 以及基于TIMP-4，其拮抗剂和抑制剂的药物组合物和治疗方法。 本发明提供了利用包含编码TIMP-4或其互补序列的核酸序列以及特异性结合TIMP-4的抗体的诊断组合物的诊断测定法。

公开(公告)号：US5902582A

公开(公告)日：1999-05-11

申请号：US699897

申请日：1996-08-15

Applicant: David T. Hung

Inventor： David T. Hung

IPC: A61K38/00 ,  A61K38/19 ,  A61K38/20 ,  A61K38/57 ,  C07K14/81 ,  C07K16/38

CPC classification number: A61K38/191 ,  A61K38/2006 ,  A61K38/204 ,  A61K38/57 ,  C07K14/8114 ,  C07K16/38

Abstract: The invention provides for the inhibition of the activity of TFPI to prevent TFPI from countering the procoagulant activities associated with many tumors. Inhibition of TFPI activity by the method of the invention facilitates the propensity toward thrombosis in malignancies and therefore promotes tumor cell death. The method of the invention also includes, in addition to the administration of an inhibitor of TFPI, co-administration of an agent capable of inducing or augmenting in the targeted tumor the release or induction of factors that initiate or enhance clotting, such as TF and Factors VIIa and Xa.

Abstract translation: 本发明提供抑制TFPI预防TFPI抵抗与许多肿瘤相关的促凝血活性的活性。 通过本发明的方法抑制TFPI活性有助于恶性肿瘤中血栓形成的倾向，从而促进肿瘤细胞死亡。 除了施用TFPI抑制剂之外，本发明的方法还包括：能够诱导或增强靶向肿瘤的药剂的共同给药，释放或诱导引发或增强凝血的因子，例如TF和 因素VIIa和Xa。

公开(公告)号：US5849875A

公开(公告)日：1998-12-15

申请号：US463323

申请日：1995-06-05

Applicant: Tze-Chein Wun ,  Kuniko K. Kretzmer ,  George J. Broze, Jr.

Inventor： Tze-Chein Wun ,  Kuniko K. Kretzmer ,  George J. Broze, Jr.

IPC: A61K38/00 ,  C07K14/81 ,  C07K16/38 ,  C12N15/12 ,  C07K14/00

CPC classification number: C07K16/38 ,  C07K14/8114 ,  A61K2039/505 ,  A61K38/00

Abstract: A cDNA clone having a base sequence for human tissue factor inhibitor (TFI) has been developed and characterized and the amino acid sequence of the TFI has been determined.

公开(公告)号：US5643752A

公开(公告)日：1997-07-01

申请号：US588163

申请日：1996-01-18

Applicant: Phillip R. Hawkins ,  Lynn E. Murry

Inventor： Phillip R. Hawkins ,  Lynn E. Murry

IPC: A61K38/00 ,  C07K14/81 ,  C07K16/38 ,  C12N15/00 ,  C12N15/11 ,  C12N15/63 ,  C12N15/85

CPC classification number: C07K16/38 ,  C07K14/8146 ,  A61K38/00

Abstract: The present invention provides a nucleic acid sequence which encodes a novel tissue inhibitor of metalloproteinases (TIMP-4) which was isolated from cells of human uterus. The invention provides for genetically engineered expression vectors and host cells comprising nucleic acid sequence encoding TIMP-4. The invention also provides for purified TIMP-4.

Abstract translation: 本发明提供了编码从人子宫细胞分离的金属蛋白酶组织抑制剂（TIMP-4）的核酸序列。 本发明提供了基因工程表达载体和包含编码TIMP-4的核酸序列的宿主细胞。 本发明还提供了纯化的TIMP-4。

公开(公告)号：US5491066A

公开(公告)日：1996-02-13

申请号：US29582

申请日：1993-03-11

Applicant: Shuichi Hiyamuta ,  Keiko Shimizu ,  Akihiko Kodota

Inventor： Shuichi Hiyamuta ,  Keiko Shimizu ,  Akihiko Kodota

IPC: C07K16/38 ,  C12N5/20 ,  C12N15/12 ,  C12P21/08 ,  G01N33/573 ,  G01N33/577

CPC classification number: C07K16/38 ,  Y10S436/811

Abstract: Disclosed is a monoclonal antibody which specifically reacts with active human ceruloplasmin as well as a method for diagnosing Wilson's disease using the same. The monoclonal antibody of the present invention specifically reacts with active human ceruloplasmin, it neutralizes the peroxidase activity of the active human ceruloplasmin upon binding thereto, and it does not specifically react with inactive human ceruloplasmin.

公开(公告)号：US5470970A

公开(公告)日：1995-11-28

申请号：US121714

申请日：1993-09-01

Applicant: Ruth Sager ,  Anthony Anisowicz ,  Zhiqiang Zou

Inventor： Ruth Sager ,  Anthony Anisowicz ,  Zhiqiang Zou

IPC: A61K38/00 ,  C07K14/47 ,  C07K14/81 ,  C07K16/38 ,  C12N15/15 ,  C12Q1/68 ,  G01N33/50 ,  G01N33/574 ,  C12N1/21 ,  C12N5/10

CPC classification number: C07K16/38 ,  C07K14/47 ,  C07K14/811 ,  C12Q1/6841 ,  C12Q1/6886 ,  G01N33/5011 ,  G01N33/57484 ,  A61K38/00 ,  C12Q2600/112 ,  C12Q2600/136 ,  C12Q2600/158 ,  Y10S530/828

Abstract: An isolated DNA encoding a polypeptide substantially identical to maspin (SEQ ID NO:1); a substantially purified preparation of maspin; an antibody specific for maspin; and use of such DNAs and antibodies in diagnostic, screening, and therapeutic methods.

Abstract translation: 编码与maspin基本相同的多肽的分离的DNA（SEQ ID NO：1）; 一种基本上纯化的maspin制剂; 对maspin具有特异性的抗体; 以及在诊断，筛选和治疗方法中使用这样的DNA和抗体。

公开(公告)号：US5422249A

公开(公告)日：1995-06-06

申请号：US121974

申请日：1993-09-15

Applicant: Manfred Liersch ,  Hans Rink ,  Walter Marki ,  Markus G. Grutter ,  Bernd Meyhack

Inventor： Manfred Liersch ,  Hans Rink ,  Walter Marki ,  Markus G. Grutter ,  Bernd Meyhack

IPC: C12N15/09 ,  A61K35/62 ,  A61K35/74 ,  A61K38/55 ,  A61P7/02 ,  C07H21/00 ,  C07H21/04 ,  C07K1/20 ,  C07K14/00 ,  C07K14/815 ,  C07K16/00 ,  C07K16/38 ,  C12N1/00 ,  C12N5/00 ,  C12N5/10 ,  C12N9/99 ,  C12N15/00 ,  C12N15/10 ,  C12N15/15 ,  C12P21/00 ,  C12P21/02 ,  C12R1/125 ,  C12R1/19 ,  C12R1/865 ,  C12N15/70

CPC classification number: C07H21/00 ,  C07K14/815 ,  C07K16/38 ,  C12N15/10

Abstract: The invention relates to DNA sequences that code for the amino acid sequence of the thrombin inhibitor hirudin, hybrid vectors containing such DNA sequences, host cells transformed with such hybrid vectors, novel polypeptides with thrombin-inhibiting activity produced from such transformed host cells, processes for the manufacture of these DNA sequences, hybrid vectors and transformed host cells, and processes for the manufacture of these thrombin-inhibitors using the transformed host cells. The hirudin compounds that can be produced according to the invention have valuable pharmacological properties.

Abstract translation: 本发明涉及编码凝血酶抑制剂水蛭素的氨基酸序列的DNA序列，含有这些DNA序列的杂交载体，用这种杂交载体转化的宿主细胞，由这种转化的宿主细胞产生的具有凝血酶抑制活性的新多肽， 这些DNA序列的制造，杂合载体和转化的宿主细胞，以及使用转化的宿主细胞制备这些凝血酶抑制剂的方法。 根据本发明可以生产的水蛭素化合物具有有价值的药理学性质。