公开(公告)号：US5968895A

公开(公告)日：1999-10-19

申请号：US762747

申请日：1996-12-11

申请人： Malcolm L. Gefter ,  Nicholas Barker ,  Gary Musso ,  Christopher J. Molineaux

发明人： Malcolm L. Gefter ,  Nicholas Barker ,  Gary Musso ,  Christopher J. Molineaux

IPC分类号： A61K47/30 ,  A61K9/22 ,  A61K38/04 ,  A61K38/09 ,  A61K38/22 ,  A61K47/34 ,  A61K47/36 ,  A61K47/38 ,  A61K47/48 ,  A61P15/00 ,  A61P15/18 ,  A61P35/00 ,  A61R38/00

CPC分类号： B82Y5/00 ,  A61K38/09 ,  A61K47/4823 ,  A61K47/48961 ,  Y10S514/80

摘要： Sustained delivery formulations comprising a water-insoluble complex of a peptide and a carrier macromolecule are disclosed. The formulations of the invention allow for loading of high concentrations of peptide in a small volume and for delivery of a pharmaceutically active peptide for prolonged periods, e.g., one month, after administration of the complex. The complexes of the invention can be milled or crushed to a fine powder. In powdered form, the complexes form stable aqueous suspensions and dispersions, suitable for injection. In a preferred embodiment, the peptide of the complex is an LHRH analogue, preferably an LHRH antagonist, and the carrier macromolecule is an anionic polymer, preferably carboxymethylcellulose. Methods of making the complexes of the invention, and methods of using LHRH-analogue-containing complexes to treat conditions treatable with an LHRH analogue, are also disclosed.

摘要翻译： 公开了包含肽和载体大分子的水不溶性络合物的持续递送制剂。 本发明的制剂允许在施用复合物之后以较小的体积装载高浓度的肽并延长药物活性肽的递送时间，例如一个月。 本发明的络合物可以研磨或粉碎成细粉末。 以粉末形式，络合物形成稳定的水性悬浮液和分散体，适于注射。 在优选的实施方案中，复合物的肽是LHRH类似物，优选LHRH拮抗剂，载体大分子是阴离子聚合物，优选羧甲基纤维素。 还公开了制备本发明复合物的方法，以及使用含LHRH类似物的复合物治疗可用LHRH类似物治疗的病症的方法。

公开(公告)号：US5169939A

公开(公告)日：1992-12-08

申请号：US296375

申请日：1989-04-09

申请人： Malcolm L. Gefter ,  Mark Ptashne ,  Jacqueline Sharon

发明人： Malcolm L. Gefter ,  Mark Ptashne ,  Jacqueline Sharon

IPC分类号： C07K16/46 ,  C12N15/62

CPC分类号： C07K16/468 ,  C12N15/62 ,  C07K2319/00 ,  C07K2319/02

摘要： Chimeric antibodies comprised of the variable region of an antibody chain contiguous with a polypeptide other than the constant region of that antibody chain are disclosed. Such chimeric antibodies can be comprised of the variable region of a chain of an immunoglobulin of selected specificity and an extrinsic polypeptide. In addition to the variable region of a chain of an immunoglobulin of selected specifity and an extrinsic polypeptide, the chimeric antibodies can include at least a portion of the constant region of an immunoglobFUNDING SOURCESThe work described herein was supported by grants from the National Institutes of Health, the American Cancer Society and the Damon Runyon--Walter Winchell Cancer Fund.

摘要翻译： 公开了由与抗体链恒定区以外的多肽连接的抗体链的可变区组成的嵌合抗体。 这样的嵌合抗体可以由所选特异性的免疫球蛋白链的可变区和外在多肽组成。 除了所选特异性的免疫球蛋白链的可变区和外在多肽之外，嵌合抗体可以包括免疫球蛋白链的恒定区的至少一部分。

公开(公告)号：US20120071329A1

公开(公告)日：2012-03-22

申请号：US13051350

申请日：2011-03-18

申请人： Barry Morgan ,  Stephen Hale ,  Christopher C. Arico-Muendel ,  Matthew Clark ,  Richard Wagner ,  David I. Israel ,  Malcolm L. Gefter ,  Dennis Benjamin ,  Nils Jakob Vest Hansen ,  Malcolm J. Kavarana ,  Steffen Phillip Creaser ,  George J. Franklin ,  Paolo A. Centrella ,  Raksha A. Acharya

发明人： Barry Morgan ,  Stephen Hale ,  Christopher C. Arico-Muendel ,  Matthew Clark ,  Richard Wagner ,  David I. Israel ,  Malcolm L. Gefter ,  Dennis Benjamin ,  Nils Jakob Vest Hansen ,  Malcolm J. Kavarana ,  Steffen Phillip Creaser ,  George J. Franklin ,  Paolo A. Centrella ,  Raksha A. Acharya

IPC分类号： C40B20/04

CPC分类号： C12N15/1068 ,  C07H21/00

摘要： The present invention provides a method for identifying a compound of interest by screening libraries of molecules which include an encoding oligonucleotide tag.

摘要翻译： 本发明提供了通过筛选包括编码寡核苷酸标签的分子文库来鉴定感兴趣的化合物的方法。

公开(公告)号：US20110251089A1

公开(公告)日：2011-10-13

申请号：US13051314

申请日：2011-03-18

申请人： Barry Morgan ,  Stephen Hale ,  Christopher C. Arico-Muendel ,  Matthew Clark ,  Richard Wagner ,  David I. Israel ,  Malcolm L. Gefter ,  Dennis Benjamin ,  Nils Jakob Vest Hansen ,  Malcolm J. Kavarana ,  Steffen Phillip Creaser ,  George J. Franklin ,  Paolo A. Centrella ,  Raksha A. Acharya

发明人： Barry Morgan ,  Stephen Hale ,  Christopher C. Arico-Muendel ,  Matthew Clark ,  Richard Wagner ,  David I. Israel ,  Malcolm L. Gefter ,  Dennis Benjamin ,  Nils Jakob Vest Hansen ,  Malcolm J. Kavarana ,  Steffen Phillip Creaser ,  George J. Franklin ,  Paolo A. Centrella ,  Raksha A. Acharya

IPC分类号： C40B30/04 ,  C40B40/06 ,  C07H21/00 ,  C12P19/34 ,  C40B50/06

CPC分类号： C12N15/1068 ,  C07H21/00 ,  C40B50/10

摘要： The present invention provides a method of synthesizing libraries of molecules which include an encoding oligonucleotide tag.

公开(公告)号：US07972994B2

公开(公告)日：2011-07-05

申请号：US11450938

申请日：2006-06-09

申请人： Barry Morgan ,  Stephen Hale ,  Christopher C. Arico-Muendel ,  Matthew Clark ,  Richard Wagner ,  David I. Israel ,  Malcolm L. Gefter ,  Dennis Benjamin ,  Nils Jakob Vest Hansen ,  Malcolm J. Kavarana ,  Steffen Phillip Creaser ,  George J. Franklin ,  Paulo A. Centrella ,  Raksha A. Acharya

发明人： Barry Morgan ,  Stephen Hale ,  Christopher C. Arico-Muendel ,  Matthew Clark ,  Richard Wagner ,  David I. Israel ,  Malcolm L. Gefter ,  Dennis Benjamin ,  Nils Jakob Vest Hansen ,  Malcolm J. Kavarana ,  Steffen Phillip Creaser ,  George J. Franklin ,  Paulo A. Centrella ,  Raksha A. Acharya

IPC分类号： C40B50/16

CPC分类号： C12N15/1068 ,  C07H21/00 ,  C40B50/10

摘要： The present invention provides methods of synthesizing libraries of molecules comprising a functional moiety which is operatively linked to an encoding oligonucleotide, wherein the encoding oligonucleotide comprises a capping sequence containing degenerate nucleotides. The methods generally include providing a solution comprising initiator compounds comprising an initial functional moiety comprising n building blocks which is operatively linked to an initial oligonucleotide; dividing the solution into reaction vessels; reacting the initiator compounds in each reaction vessel with a building block comprising a complementary reactive group to form a covalent bond; and reacting the initial oligonucleotide in each aliquot with a distinct incoming oligonucleotide in the presence of an enzyme which catalyzes the ligation of the incoming oligonucleotide and the initial oligonucleotide, under conditions suitable for enzymatic ligation of the incoming oligonucleotide and the initial oligonucleotide to form an encoding oligonucleotide.

摘要翻译： 本发明提供了合成包含与编码寡核苷酸有效连接的功能部分的分子文库的方法，其中编码寡核苷酸包含含有简并核苷酸的封端序列。 所述方法通常包括提供包含引发剂化合物的溶液，所述引发剂化合物包含初始功能部分，其包含可操作地连接于初始寡核苷酸的n 将溶液分解成反应容器; 使每个反应容器中的引发剂化合物与包含互补反应性基团的构建块反应形成共价键; 并且在适合于引入寡核苷酸和初始寡​​核苷酸的酶连接的条件下，在催化引入的寡核苷酸和初始寡​​核苷酸的连接的酶存在下，使各等分试样中的初始寡核苷酸与不同的入侵寡核苷酸反应，形成编码 寡核苷酸。

公开(公告)号：US20110136697A1

公开(公告)日：2011-06-09

申请号：US13023599

申请日：2011-02-09

申请人： Barry MORGAN ,  Stephen Hale ,  Christopher C. Arico-Muendel ,  Matthew Clark ,  Richard Wagner ,  David I. Israel ,  Malcolm L. Gefter ,  Dennis Benjamin ,  Nils Jakob Vest Hansen ,  Malcolm J. Kavarana ,  Steffen Phillip Creaser ,  George J. Franklin ,  Paolo A. Centrella ,  Raksha A. Acharya

发明人： Barry MORGAN ,  Stephen Hale ,  Christopher C. Arico-Muendel ,  Matthew Clark ,  Richard Wagner ,  David I. Israel ,  Malcolm L. Gefter ,  Dennis Benjamin ,  Nils Jakob Vest Hansen ,  Malcolm J. Kavarana ,  Steffen Phillip Creaser ,  George J. Franklin ,  Paolo A. Centrella ,  Raksha A. Acharya

IPC分类号： C40B50/06

CPC分类号： C07H21/00 ,  C12N15/1068 ,  C40B50/10

摘要： The present invention provides a method of synthesizing libraries of molecules which include an encoding oligonucleotide tag.

摘要翻译： 本发明提供合成包含编码寡核苷酸标签的分子文库的方法。

公开(公告)号：US06689752B2

公开(公告)日：2004-02-10

申请号：US09895443

申请日：2001-06-29

申请人： Mark A. Findeis ,  Malcolm L. Gefter ,  Gary Musso ,  Ethan R. Signer ,  James Wakefield ,  Susan Molineaux ,  Joseph Chin ,  Jung-Ja Lee ,  Michael Kelley ,  Sonja Komar-Panicucci ,  Christopher C. Arico-Muendel ,  Kathryn Phillips ,  Neil J. Hayward

发明人： Mark A. Findeis ,  Malcolm L. Gefter ,  Gary Musso ,  Ethan R. Signer ,  James Wakefield ,  Susan Molineaux ,  Joseph Chin ,  Jung-Ja Lee ,  Michael Kelley ,  Sonja Komar-Panicucci ,  Christopher C. Arico-Muendel ,  Kathryn Phillips ,  Neil J. Hayward

IPC分类号： A61K3807

CPC分类号： C07K5/101 ,  A61K38/00 ,  C07K5/1027 ,  C07K7/06 ,  C07K14/4711 ,  G01N33/6896 ,  G01N2333/4709 ,  G01N2800/2821

摘要： Compounds that modulate natural &bgr; amyloid peptide aggregation are provided. The modulators of the invention comprise a peptide, preferably based on a &bgr; amyloid peptide, that is comprised entirely of D-amino acids. Preferably, the peptide comprises 3-5 D-amino acid residues and includes at least two D-amino acid residues independently selected from the group consisting of D-leucine, D-phenylalanine and D-valine. In a particularly preferred embodiment, the peptide is a retro-inverso isomer of a &bgr; amyloid peptide, preferably a retro-inverso isomer of A&bgr;17-21. In certain embodiments, the peptide is modified at the amino-terminus, the carboxy-terminus, or both. Preferred amino-terminal modifying groups include cyclic, heterocyclic, polycyclic and branched alkyl groups. Preferred carboxy-terminal modifying groups include an amide group, an alkyl amide group, an aryl amide group or a hydroxy group. Pharmaceutical compositions comprising the compounds of the invention, and diagnostic and treatment methods for amyloidogenic diseases using the compounds of the invention, are also disclosed.

摘要翻译： 提供调节天然β淀粉样肽聚集的化合物。 本发明的调节剂包含优选基于β-淀粉样肽的肽，其完全由D-氨基酸组成。 优选地，肽包含3-5个D-氨基酸残基，并且包括独立地选自D-亮氨酸，D-苯丙氨酸和D-缬氨酸的至少两个D-氨基酸残基。 在特别优选的实施方案中，肽是β淀粉样肽的逆反异构体，优选Abeta17-21的逆反异构体。 在某些实施方案中，肽在氨基末端，羧基末端或两者都被修饰。 优选的氨基末端修饰基团包括环状，杂环，多环和支链烷基。 优选的羧基末端修饰基团包括酰胺基，烷基酰胺基，芳基酰胺基或羟基。 还公开了包含本发明化合物的药物组合物，以及使用本发明化合物的淀粉样变性疾病的诊断和治疗方法。

公开(公告)号：US06277826B1

公开(公告)日：2001-08-21

申请号：US09356931

申请日：1999-07-19

申请人： Mark A. Findeis ,  Malcolm L. Gefter ,  Gary Musso ,  Ethan R. Signer ,  James Wakefield ,  Susan Molineaux ,  Joseph Chin ,  Jung-Ja Lee ,  Michael Kelley ,  Sonja Komar-Panicucci ,  Christopher C. Arico-Muendel ,  Kathryn Phillips ,  Neil J. Hayward

发明人： Mark A. Findeis ,  Malcolm L. Gefter ,  Gary Musso ,  Ethan R. Signer ,  James Wakefield ,  Susan Molineaux ,  Joseph Chin ,  Jung-Ja Lee ,  Michael Kelley ,  Sonja Komar-Panicucci ,  Christopher C. Arico-Muendel ,  Kathryn Phillips ,  Neil J. Hayward

IPC分类号： A61K3806

CPC分类号： C07K5/101 ,  A61K38/00 ,  C07K5/1027 ,  C07K7/06 ,  C07K14/4711 ,  G01N33/6896 ,  G01N2333/4709 ,  G01N2800/2821

摘要： Compounds that modulate natural &bgr; amyloid peptide aggregation are provided. The modulators of the invention comprise a peptide, preferably based on a &bgr; amyloid peptide, that is comprised entirely of D-amino acids. Preferably, the peptide comprises 3-5 D-amino acid residues and includes at least two D-amino acid residues independently selected from the group consisting of D-leucine, D-phenylalanine and D-valine. In a particularly preferred embodiment, the peptide is a retro-inverso isomer of a &bgr; amyloid peptide, preferably a retro-inverso isomer of A&bgr;17-21. In certain embodiments, the peptide is modified at the amino-terminus, the carboxy-terminus, or both. Preferred amino-terminal modifying groups include cyclic, heterocyclic, polycyclic and branched alkyl groups. Preferred carboxy-terminal modifying groups include an amide group, an alkyl amide group, an aryl amide group or a hydroxy group. Pharmaceutical compositions comprising the compounds of the invention, and diagnostic and treatment methods for amyloidogenic diseases using the compounds of the invention, are also disclosed.

摘要翻译： 提供调节天然β淀粉样肽聚集的化合物。 本发明的调节剂包含优选基于β-淀粉样肽的肽，其完全由D-氨基酸组成。 优选地，肽包含3-5个D-氨基酸残基，并且包括独立地选自D-亮氨酸，D-苯丙氨酸和D-缬氨酸的至少两个D-氨基酸残基。 在特别优选的实施方案中，肽是β淀粉样肽的逆反异构体，优选Abeta17-21的逆反异构体。 在某些实施方案中，肽在氨基末端，羧基末端或两者都被修饰。 优选的氨基末端修饰基团包括环状，杂环，多环和支链烷基。 优选的羧基末端修饰基团包括酰胺基，烷基酰胺基，芳基酰胺基或羟基。 还公开了包含本发明化合物的药物组合物，以及使用本发明化合物的淀粉样变性疾病的诊断和治疗方法。

公开(公告)号：US5854204A

公开(公告)日：1998-12-29

申请号：US612785

申请日：1996-03-14

申请人： Mark A. Findeis ,  Howard Benjamin ,  Marc B. Garnick ,  Malcolm L. Gefter ,  Arvind Hundal ,  Laura Kasman ,  Gary Musso ,  Ethan R. Signer ,  James Wakefield ,  Michael Reed ,  Susan Molineaux ,  William Kubasek ,  Joseph Chin ,  Jung-Ja Lee ,  Michael Kelley

发明人： Mark A. Findeis ,  Howard Benjamin ,  Marc B. Garnick ,  Malcolm L. Gefter ,  Arvind Hundal ,  Laura Kasman ,  Gary Musso ,  Ethan R. Signer ,  James Wakefield ,  Michael Reed ,  Susan Molineaux ,  William Kubasek ,  Joseph Chin ,  Jung-Ja Lee ,  Michael Kelley

IPC分类号： A61K39/02 ,  A61K31/00 ,  A61K38/00 ,  A61K51/00 ,  A61P25/00 ,  C07K7/06 ,  C07K14/47 ,  C07K14/435 ,  C07K7/08

CPC分类号： C07K14/4711 ,  A61K38/00

摘要： Compounds that modulate the aggregation of amyloidogenic proteins or peptides are disclosed. The modulators of the invention can promote amyloid aggregation or, more preferably, can inhibit natural amyloid aggregation. In a preferred embodiment, the compounds modulate the aggregation of natural .beta. amyloid peptides (.beta.-AP). In a preferred embodiment, the .beta. amyloid modulator compounds of the invention are comprised of an A.beta. aggregation core domain and a modifying group coupled thereto such that the compound alters the aggregation or inhibits the neurotoxicity of natural .beta. amyloid peptides when contacted with the peptides. Furthermore, the modulators are capable of altering natural .beta.-AP aggregation when the natural .beta.-APs are in a molar excess amount relative to the modulators. Pharmaceutical compositions comprising the compounds of the invention, and diagnostic and treatment methods for amyloidogenic diseases using the compounds of the invention, are also disclosed.

摘要翻译： 公开了调节淀粉样蛋白形成蛋白或肽聚集的化合物。 本发明的调节剂可以促进淀粉样蛋白聚集，更优选可以抑制天然淀粉样蛋白聚集。 在优选的实施方案中，化合物调节天然β淀粉样蛋白肽（β-AP）的聚集。 在优选的实施方案中，本发明的β淀粉样蛋白调节剂化合物由Aβ聚集核心结构域和与其偶联的修饰基团组成，使得当与肽接触时，该化合物改变聚集或抑制天然β淀粉样肽的神经毒性。 此外，当天然β-APs相对于调节剂摩尔过量时，调节剂能够改变天然的β-AP聚集。 还公开了包含本发明化合物的药物组合物，以及使用本发明化合物的淀粉样变性疾病的诊断和治疗方法。

公开(公告)号：US5780435A

公开(公告)日：1998-07-14

申请号：US573109

申请日：1995-12-15

申请人： Marc B. Garnick ,  Christopher J. Molineaux ,  Malcolm L. Gefter

发明人： Marc B. Garnick ,  Christopher J. Molineaux ,  Malcolm L. Gefter

IPC分类号： A61K38/00 ,  A61K38/04 ,  A61K38/09

CPC分类号： A61K38/09 ,  Y10S514/80

摘要： Methods for treating prostate cancer are disclosed. The methods of the invention generally feature administration to a subject of an LHRH-R antagonist, in combination with a second therapy. In one embodiment, this second therapy is performance of a procedure that removes or destroys prostatic tumor tissue, such as a radical prostatectomy, cryosurgery or X-ray therapy (external or interstitial). In another embodiment, the second therapy is treatment with an LHRH-R agonist, either simultaneous with or subsequent to LHRH-R antagonist therapy. The methods of the invention can further involve administering an antiandrogen and/or an inhibitor of sex steroid biosynthesis to the subject in combination with the LHRH-R antagonist.