公开(公告)号：US09649295B2

公开(公告)日：2017-05-16

申请号：US10586929

申请日：2005-01-20

申请人： Jochen Buck ,  Lonny R. Levin ,  Fritz A. Muhlschlegel

发明人： Jochen Buck ,  Lonny R. Levin ,  Fritz A. Muhlschlegel

IPC分类号： A61K31/415 ,  A61K31/4184 ,  C12Q1/527

CPC分类号： A61K31/415 ,  A61K31/4184 ,  C12Q1/527 ,  G01N2333/988 ,  Y02A50/411

摘要： The present invention relates to a method of treating a disorder mediated by soluble adenylyl cyclase in a subject. The method involves administering to a subject an effective amount of a compound disclosed herein that modulates soluble adenylyl cyclase, under conditions effective to treat the disorder mediated by soluble adenylyl cyclase. The present invention also relates to a method of treating a disorder mediated by soluble adenylyl cyclase in a subject, where the disorder is selected from the group consisting of: learning or memory disorders, malaria, fungal infection, spinal cord injury, Alzheimer's disease, amyotrophic lateral sclerosis, and peripheral neuropathy. The method involves modulating soluble adenylyl cyclase in the subject. Another aspect of the present invention relates to a method of modulating soluble adenylyl cyclase. The method involves contacting eukaryotic cells with a compound that modulates soluble adenylyl cyclase, under conditions effective to modulate soluble adenylyl cyclase.

公开(公告)号：US08859213B2

公开(公告)日：2014-10-14

申请号：US13642475

申请日：2011-04-06

申请人： Cynthia Magro ,  Jonathan Zippin ,  Lonny R. Levin ,  Jochen Buck

发明人： Cynthia Magro ,  Jonathan Zippin ,  Lonny R. Levin ,  Jochen Buck

IPC分类号： G01N33/53 ,  G01N33/574 ,  G01N33/50 ,  C12Q1/527 ,  G01N33/68

CPC分类号： G01N33/5743 ,  C12Q1/527 ,  G01N33/5026 ,  G01N33/5044 ,  G01N33/5076 ,  G01N33/6893 ,  G01N2800/20 ,  G01N2800/56

摘要： The invention provides a method for diagnosing a melanocytic proliferation in a subject comprising staining a sample of lesional melanocytes with an antibody against soluble adenylyl cyclase (sAC) and interpreting the sAC staining pattern, which is associated with a diagnosis of a melanocytic proliferation. The sAC staining pattern, which is complex, is discriminatory and distinctive according to the nature of the melanocytic proliferation. The sAC staining pattern comprises one or more of dot-like Golgi staining, broad granular Golgi staining, diffuse cytoplasmic staining, nucleolar staining, incomplete granular nuclear staining, and pan-nuclear staining. The method of the invention is particularly useful in confirming or disaffirming a diagnosis reached through conventional histologic examination of a sample. Additionally, the invention provides a kit for use in interpreting melanocytic proliferations.

摘要翻译： 本发明提供了用于诊断受试者中黑素细胞增殖的方法，其包括用针对可溶性腺苷酸环化酶（sAC）的抗体染色病变黑素细胞样品，并解释与诊断黑素细胞增殖相关的sAC染色模式。 根据黑素细胞增殖的性质，复杂的sAC染色模式具有歧视性和独特性。 sAC染色模式包括点状高尔基体染色，宽粒状高尔基体染色，弥漫性细胞质染色，核仁染色，不完全粒状核染色和泛核染色中的一种或多种。 本发明的方法特别可用于确认或不肯定通过常规的样品组织学检查达成的诊断。 另外，本发明提供了用于解释黑素细胞增殖的试剂盒。

公开(公告)号：US06544768B1

公开(公告)日：2003-04-08

申请号：US09568407

申请日：2000-05-11

申请人： Jochen Buck ,  Lonny R. Levin

发明人： Jochen Buck ,  Lonny R. Levin

IPC分类号： C12N988

CPC分类号： C12N9/88 ,  A61K38/00

摘要： The invention provides isolated animal soluble adenylyl cyclase and methods of modulating its expression and activity. Also provided are methods of utilizing soluble adenylyl cyclase for diagnosing pathological conditions and monitoring blood gases.

摘要翻译： 本发明提供了分离的动物可溶性腺苷酸环化酶和调节其表达和活性的方法。 还提供了利用可溶性腺苷酸环化酶诊断病理状况和监测血液气体的方法。

公开(公告)号：US20130065246A1

公开(公告)日：2013-03-14

申请号：US13642475

申请日：2011-04-06

申请人： Cynthia Magro ,  Jonathan Zippin ,  Lonny R. Levin ,  Jochen Buck

发明人： Cynthia Magro ,  Jonathan Zippin ,  Lonny R. Levin ,  Jochen Buck

IPC分类号： G01N33/574 ,  G01N33/577

CPC分类号： G01N33/5743 ,  C12Q1/527 ,  G01N33/5026 ,  G01N33/5044 ,  G01N33/5076 ,  G01N33/6893 ,  G01N2800/20 ,  G01N2800/56

摘要： The invention provides a method for diagnosing a melanocytic proliferation in a subject comprising staining a sample of lesional melanocytes with an antibody against soluble adenylyl cyclase (sAC) and interpreting the sAC staining pattern, which is associated with a diagnosis of a melanocytic proliferation. The sAC staining pattern, which is complex, is discriminatory and distinctive according to the nature of the melanocytic proliferation. The sAC staining pattern comprises one or more of dot-like Golgi staining, broad granular Golgi staining, diffuse cytoplasmic staining, nucleolar staining, incomplete granular nuclear staining, and pan-nuclear staining. The method of the invention is particularly useful in confirming or disaffirming a diagnosis reached through conventional histologic examination of a sample. Additionally, the invention provides a kit for use in interpreting melanocytic proliferations.

摘要翻译： 本发明提供了一种用于诊断受试者中黑素细胞增殖的方法，包括用针对可溶性腺苷酸环化酶（sAC）的抗体染色病变黑素细胞样品，并解释与诊断黑素细胞增殖相关的sAC染色模式。 根据黑素细胞增殖的性质，复杂的sAC染色模式具有歧视性和独特性。 sAC染色模式包括点状高尔基体染色，宽粒状高尔基体染色，弥漫性细胞质染色，核仁染色，不完全粒状核染色和泛核染色中的一种或多种。 本发明的方法特别可用于确认或不肯定通过常规的样品组织学检查达成的诊断。 另外，本发明提供了用于解释黑素细胞增殖的试剂盒。

公开(公告)号：US09017681B2

公开(公告)日：2015-04-28

申请号：US12523011

申请日：2008-01-11

申请人： Lonny Levin ,  Jochen Buck ,  Leo Brizuela ,  Michael Pinnisi

发明人： Lonny Levin ,  Jochen Buck ,  Leo Brizuela ,  Michael Pinnisi

IPC分类号： A61K31/122 ,  A61K31/415

CPC分类号： A61K31/415 ,  G01N2333/988 ,  G01N2500/00

摘要： The present invention relates to a method of preventing or treating a disease caused by bacterial infection by administering an effective amount of a modulator of bacterial adenylyl cyclase. The invention also provides pharmaceutical compositions useful for preventing or treating a disease, with the compositions containing a therapeutically effective amount of a modulator of bacterial adenylyl cyclase. The invention also provides screening methods for identifying selective modulators of bacterial adenylyl cyclase that do not substantially modulate adenylyl cyclase of the subject. The invention also provides methods for culturing bacterial pathogens and methods for inducing the pathogenic state in vitro.

摘要翻译： 本发明涉及通过施用有效量的细菌腺苷酸环化酶调节剂来预防或治疗由细菌感染引起的疾病的方法。 本发明还提供了可用于预防或治疗疾病的药物组合物，其中组合物含有治疗有效量的细菌腺苷酸环化酶调节剂。 本发明还提供了用于鉴定细菌腺苷酸环化酶的选择性调节剂的筛选方法，所述选择性调节剂基本上不调节受试者的腺苷酸环化酶。 本发明还提供培养细菌病原体的方法和在体外诱导致病状态的方法。

公开(公告)号：US6001803A

公开(公告)日：1999-12-14

申请号：US325240

申请日：1994-10-20

申请人： Peter Besmer ,  Jochen Buck ,  Malcolm A. S. Moore ,  Karl Nocka

发明人： Peter Besmer ,  Jochen Buck ,  Malcolm A. S. Moore ,  Karl Nocka

IPC分类号： A61K38/00 ,  A61K38/18 ,  A61K38/19 ,  A61K38/04 ,  C07K14/525 ,  C07K14/535

CPC分类号： A61K38/18 ,  A61K38/191 ,  A61K38/193 ,  C12N5/0639 ,  C12N5/0647 ,  C12N2501/125 ,  C12N2501/14 ,  C12N2501/21 ,  C12N2501/22 ,  C12N2501/2301 ,  C12N2501/2303 ,  C12N2501/2306 ,  C12N2501/25

摘要： A pharmaceutical composition which comprises the c-kit ligand (KL) purified by applicants or produced by applicants' recombinant methods in combination with other hematopoietic factors and a pharmaceutically acceptable carrier is provided as well as methods of treating patients which comprise administering to the patient the pharmaceutical composition of this invention. This invention provides combination therapies using c-kit ligand (KL) and a purified c-kit ligand (KL) polypeptide, or a soluble fragment thereof and other hematopoietic factors. It also provides methods and compositions for ex-vivo use of KL alone or in combination therapy. A mutated KL antagonist is also described. Such an antagonist may also be a small molecule. Antisense nucleic acids to KL as therapeutics are also described. Lastly, compositions and methods are described that take advantage of the role of KL in germ cells, mast cells and melanocytes.

摘要翻译： 提供了包含通过申请人纯化或由申请人的重组方法与其他造血因子组合产生的c-kit配体（KL）和药学上可接受的载体的药物组合物，以及治疗患者的方法，其包括向患者施用 本发明的药物组合物。 本发明提供了使用c-kit配体（KL）和纯化的c-kit配体（KL）多肽或其可溶性片段和其他造血因子的组合疗法。 它还提供单独使用KL或联合治疗的离体使用KL方法和组合物。 还描述了突变的KL拮抗剂。 这样的拮抗剂也可以是小分子。 还描述了作为治疗剂的KL的反义核酸。 最后，描述了利用KL在生殖细胞，肥大细胞和黑素细胞中的作用的组合物和方法。

公开(公告)号：US5521221A

公开(公告)日：1996-05-28

申请号：US682909

申请日：1991-04-09

申请人： Jochen Buck ,  Ulrich Hammerling ,  Fadila Derguini ,  Koji Nakanishi

发明人： Jochen Buck ,  Ulrich Hammerling ,  Fadila Derguini ,  Koji Nakanishi

IPC分类号： A01N37/18 ,  A01N37/34 ,  A61K31/07 ,  A61K31/23 ,  A61K31/70 ,  C07C403/08 ,  C07D303/14 ,  C07D317/20 ,  C07F7/18 ,  C12N1/38 ,  C12N5/078 ,  C12N5/0783 ,  C12N15/67 ,  C12P17/02 ,  C12P23/00 ,  C07C35/18 ,  C07C37/68

CPC分类号： C12P23/00 ,  C07C403/08 ,  C07C403/10 ,  C07C403/12 ,  C07D303/14 ,  C07F7/184 ,  C12N15/67 ,  C12N5/065 ,  C07B2200/09 ,  C07C2101/14 ,  C07C2101/16 ,  C12N2501/385

摘要： This invention provides a purified retro-retinoid compound characterized by a molecular mass of about 302 daltons. Also provided by this invention is a method of enhancing the growth of a cell in a vitamin A reduced environment which comprises contacting the cell with an effective growth enhancing amount of a compound having a structure: ##STR1## wherein the configuration of the C6, C8, C10 and C12 double bond independently is Z or E and the absolute configuration at C-14 is independently R or S; wherein R.sub.1 is alkyl, alkyl halide, alcohol, ester, ether, aldehyde, ketone, carboxylic acid, carboxylic ester, acid halide, amide, nitrile, or amine; and wherein R.sub.2 is hydroxyl, halide, alkoxy, ester, alkyl, alcohol, ether, aldehyde, ketone, carboxylic acid, carboxylic ester, nitrile, amine, azide, alkyl halide, acid halide, acid azide, or amide; or wherein R.sub.1 and R.sub.2 are replaced by a 14, 15-oxirane group; and wherein the retro structure is alpha or gamma. Further provided are a method for enhancing transcription of a gene regulated by retinoid in a cell, or a method for enhancing an immune response in a subject.

摘要翻译： 本发明提供了一种以分子质量为约302道尔顿为特征的纯化的后视色素化合物。 本发明还提供了增强维生素A还原环境中细胞生长的方法，其包括使细胞与有效生长增加量的具有以下结构的化合物接触：其中C6，C8的构型 ，C10和C12双键独立地为Z或E，C-14的绝对构型独立地为R或S; 其中R1是烷基，烷基卤，醇，酯，醚，醛，酮，羧酸，羧酸酯，酰卤，酰胺，腈或胺; 烷基，醇，醚，醛，酮，羧酸，羧酸酯，腈，胺，叠氮化物，烷基卤，酰卤，叠氮化物或酰胺; 或其中R 1和R 2被14,15-环氧乙烷基团取代; 并且其中所述复古结构是α或γ。 还提供了增强细胞中类视黄醇调节基因转录的方法，或增强受试者的免疫应答的方法。

公开(公告)号：US06403559B1

公开(公告)日：2002-06-11

申请号：US09371261

申请日：1999-08-10

申请人： Peter Besmer ,  Jochen Buck ,  Malcolm A. S. Moore ,  Karl Nocka

发明人： Peter Besmer ,  Jochen Buck ,  Malcolm A. S. Moore ,  Karl Nocka

IPC分类号： A61K3804

CPC分类号： A61K31/7072 ,  A61K38/00 ,  A61K38/193 ,  A61K38/202 ,  C07K14/475 ,  C07K14/52 ,  C07K14/705 ,  C07K14/71 ,  C07K14/715 ,  C07K16/22 ,  C12N15/87 ,  A61K2300/00

摘要： A pharmaceutical composition which comprises the c-kit ligand (KL) purified by applicants or produced by applicants' recombinant methods in combination with other hematopoietic factors and a pharmaceutically acceptable carrier is provided as well as methods of treating patients which comprise administering to the patient the pharmaceutical composition of this invention. This invention provides combination therapies using c-kit ligand (KL) and a purified c-kit ligand (KL) polypeptide, or a soluble fragment thereof and other hematopoietic factors. It also provides methods and compositions for ex-vivo use of KL alone or in combination therapy. A mutated KL antagonist is also described. Such an antagonist may also be a small molecule. Antisense nucleic acids to KL as therapeutics are also described. Lastly, compositions and methods are described that take advantage of the role of KL in germ cells, mast cells and melanocytes.

摘要翻译： 提供了包含通过申请人纯化或由申请人的重组方法与其他造血因子组合产生的c-kit配体（KL）和药学上可接受的载体的药物组合物，以及治疗患者的方法，其包括向患者施用 本发明的药物组合物。 本发明提供了使用c-kit配体（KL）和纯化的c-kit配体（KL）多肽或其可溶性片段和其他造血因子的组合疗法。 它还提供单独使用KL或联合治疗的离体使用KL方法和组合物。 还描述了突变的KL拮抗剂。 这样的拮抗剂也可以是小分子。 还描述了作为治疗剂的KL的反义核酸。 最后，描述了利用KL在生殖细胞，肥大细胞和黑素细胞中的作用的组合物和方法。

公开(公告)号：US5883136A

公开(公告)日：1999-03-16

申请号：US478411

申请日：1995-06-07

申请人： Ulrich Hammerling ,  Jochen Buck ,  Fadila Derguini ,  Koji Nakanishi

发明人： Ulrich Hammerling ,  Jochen Buck ,  Fadila Derguini ,  Koji Nakanishi

IPC分类号： A61K31/015 ,  A61K31/045 ,  A61K31/07 ,  A61K31/075 ,  A61K31/22 ,  A61K31/23

CPC分类号： A61K31/07 ,  A61K31/015 ,  A61K31/045 ,  A61K31/075 ,  A61K31/22 ,  A61K31/23

摘要： This invention provides methods of inhibiting the growth of cells, of treating a subject having a disease characterized by an uncontrolled growth of cells and of blocking an immune response as well as related inflammatory responses in a subject which comprises administering a compound having the structure: ##STR1##

摘要翻译： 本发明提供了抑制细胞生长的方法，该方法包括给予具有以下结构的化合物：治疗患有特征在于细胞不受控生长并且阻断免疫应答以及相关炎症反应的疾病的受试者， 图像>

公开(公告)号：US5767074A

公开(公告)日：1998-06-16

申请号：US341456

申请日：1994-11-17

申请人： Peter Besmer ,  Jochen Buck ,  Malcolm A.S. Moore ,  Karl Nocka

发明人： Peter Besmer ,  Jochen Buck ,  Malcolm A.S. Moore ,  Karl Nocka

IPC分类号： A61K38/00 ,  A61K38/17 ,  A61K38/18 ,  A61K38/19 ,  C07K14/475 ,  C07K14/52 ,  C07K14/705 ,  C07K14/71 ,  C07K14/715 ,  C07K16/22 ,  C12N15/87 ,  A61K38/04 ,  C07K14/435

CPC分类号： C12N15/87 ,  A61K38/193 ,  A61K38/2006 ,  A61K38/202 ,  A61K38/204 ,  C07K14/475 ,  C07K14/52 ,  C07K14/705 ,  C07K14/71 ,  C07K14/715 ,  C07K16/22 ,  A61K38/00

摘要： A pharmaceutical composition which comprises the c-kit ligand (KL) purified by applicants or produced by applicants' recombinant methods in combination with other hematopoietic factors and a pharmaceutically acceptable carrier is provided as well as methods of treating patients which comprise administering to the patient the pharmaceutical composition of this invention. This invention provides combination therapies using c-kit ligand (KL) and a purified c-kit ligand (KL) polypeptide, or a soluble fragment thereof and other hematopoietic factors. It also provides methods and compositions for ex-vivo use of KL alone or in combination therapy. A mutated KL antagonist is also described. Such an antagonist may also be a small molecule. Antisense nucleic acids to KL as therapeutics are also described. Lastly, compositions and methods are described that take advantage of the role of KL in germ cells, mast cells and melanocytes.

摘要翻译： 提供了包含通过申请人纯化或由申请人的重组方法与其他造血因子组合产生的c-kit配体（KL）和药学上可接受的载体的药物组合物，以及治疗患者的方法，其包括向患者施用 本发明的药物组合物。 本发明提供了使用c-kit配体（KL）和纯化的c-kit配体（KL）多肽或其可溶性片段和其他造血因子的组合疗法。 它还提供单独使用KL或联合治疗的离体使用KL方法和组合物。 还描述了突变的KL拮抗剂。 这样的拮抗剂也可以是小分子。 还描述了作为治疗剂的KL的反义核酸。 最后，描述了利用KL在生殖细胞，肥大细胞和黑素细胞中的作用的组合物和方法。