公开(公告)号：WO2012082618A3

公开(公告)日：2012-06-21

申请号：PCT/US2011/064407

申请日：2011-12-12

Applicant: IMMUNOMEDICS, INC. ,  D'SOUZA, Christopher, A. ,  MCBRIDE, William, J. ,  GOLDENBERG, David, M.

Inventor： D'SOUZA, Christopher, A. ,  MCBRIDE, William, J. ,  GOLDENBERG, David, M.

IPC: A61K31/33 ,  C07D225/00 ,  C07D255/02

Abstract: The present application discloses compositions and methods of synthesis and use of 18 F or 19 F-labeled molecules of use in PET, SPECT and/or MR imaging. Preferably, the 18F or 19 F is conjugated to a targeting molecule by formation of a complex with a group IIIA metal and binding of the complex to a bifunctional chelating agent, which may be directly or indirectly attached to the targeting molecule. In other embodiments, the 18 F or 19 F labeled moiety may comprise a targetable construct used in combination with a bispecific antibody to target a disease-associated antigen. The disclosed methods and compositions allow the simple and reproducible labeling of molecules at very high efficiency and specific activity in 30 minutes or less. In preferred embodiments, the labeled molecule may be used for imaging in a subject without purification after labeling.

公开(公告)号：WO2005069994A3

公开(公告)日：2009-04-16

申请号：PCT/US2005002193

申请日：2005-01-24

Applicant: IMMUNOMEDICS INC ,  HANSEN HANS J ,  MCBRIDE WILLIAM J ,  GOLDENBERG DAVID M ,  ROSSI EDMUND A ,  CHANG CHIEN-HSING KEN

Inventor： HANSEN HANS J ,  MCBRIDE WILLIAM J ,  GOLDENBERG DAVID M ,  ROSSI EDMUND A ,  CHANG CHIEN-HSING KEN

IPC: A61K39/395 ,  A01N43/04 ,  A61K38/00 ,  A61K38/43 ,  A61K47/48 ,  A61K48/00 ,  A61K51/00 ,  C07H21/02 ,  C07K14/47 ,  C07K14/705 ,  C07K16/00 ,  C12N9/02 ,  C12N9/22

CPC classification number: C12N9/22 ,  A61K33/24 ,  A61K38/00 ,  A61K38/19 ,  A61K45/06 ,  A61K47/551 ,  C07K14/705 ,  A61K2300/00

Abstract: Disclosed are conjugates and complexes that include a folate receptor ligand and one or more therapeutic molecules, such as onconase or a variant thereof such as rapLR1. The conjugates and complexes may be useful as primary therapeutic agents, which may be administered with additional therapeutic or diagnostic agents. Also disclosed are kits that include the conjugates and complexes.

Abstract translation: 公开了包含叶酸受体配体和一种或多种治疗分子（例如onconase或其变体）如rapLR1的缀合物和复合物。 缀合物和复合物可用作主要治疗剂，其可以与另外的治疗剂或诊断剂一起施用。 还公开了包含缀合物和复合物的试剂盒。

公开(公告)号：WO2005077071A3

公开(公告)日：2009-04-09

申请号：PCT/US2005004177

申请日：2005-02-11

Applicant: IMMUNOMEDICS INC ,  MCBRIDE WILLIAM J ,  GOLDENBERG DAVID M ,  NOREN CARL ,  HANSEN HANS J

Inventor： MCBRIDE WILLIAM J ,  GOLDENBERG DAVID M ,  NOREN CARL ,  HANSEN HANS J

IPC: A61K39/395 ,  A01N37/02 ,  A61K47/48 ,  A61K51/00 ,  A61K51/04 ,  A61K51/08 ,  A61K51/10 ,  C07C69/74 ,  C07K7/06 ,  C07K16/18 ,  C07K16/30 ,  C07K16/44 ,  C07K16/46

CPC classification number: A61K51/0497 ,  A61K47/665 ,  A61K51/04 ,  A61K51/0455 ,  A61K51/048 ,  A61K51/1048 ,  A61K51/1063 ,  A61K2039/505 ,  B82Y5/00 ,  C07K5/06078 ,  C07K5/1013 ,  C07K5/1016 ,  C07K5/1019 ,  C07K7/06 ,  C07K16/18 ,  C07K16/3007 ,  C07K16/3046 ,  C07K16/44 ,  C07K16/468 ,  C07K2317/12 ,  C07K2317/13 ,  C07K2317/24 ,  C07K2317/31 ,  C07K2317/55 ,  C07K2317/622 ,  C07K2319/00

Abstract: Disclosed are compounds that include two or more haptens conjugated by a spacer or a carrier. The haptens may include diethylenetriaminepentaacetate (DTPA), histimine-succinyl-glutamine (HSG), or combinations of DTPA and HSG. The compound also includes an effector molecule which may be conjugated to one or more of the haptens, the spacer/carrier, or both. The effector molecule may be conjugated by a number of linkages including an ester linkage, an imino linkage, an amino linkage, a sulfide linkage, a thiosemicarbazone linkage, a semicarbazone linkage, an oxime linkage, an ether linkage, or combinations of these linkages. Also disclosed are methods of synthesizing the compounds and/or precursors of the compounds.

Abstract translation: 公开了包含两个或多个通过间隔物或载体缀合的半抗原的化合物。 半抗原可以包括二亚乙基三胺五乙酸（DTPA），组氨酰胺 - 琥珀酰 - 谷氨酰胺（HSG）或DTPA和HSG的组合。 该化合物还包括可与半抗原，间隔物/载体或两者中的一个或多个缀合的效应分子。 效应分子可以通过多个键连接，包括酯键，亚氨基键，氨基键，硫键，硫代缩氨基脲键，缩氨基脲键，肟键，醚键或这些键的组合。 还公开了合成化合物的化合物和/或前体的方法。

公开(公告)号：WO2006107786A3

公开(公告)日：2008-08-07

申请号：PCT/US2006012084

申请日：2006-03-29

Applicant: IBC PHARMACEUTICALS INC ,  CHIEN HSING CHANG ,  GOLDENBERG DAVID M ,  MCBRIDE WILLIAM J ,  ROSSI EDMUND A

Inventor： CHIEN HSING CHANG ,  GOLDENBERG DAVID M ,  MCBRIDE WILLIAM J ,  ROSSI EDMUND A

IPC: A61K39/00 ,  A61K39/385 ,  A61K39/395 ,  A61K39/44 ,  C07K2/00 ,  C07K16/00 ,  C07K16/18 ,  C07K16/24 ,  C07K16/28 ,  C07K16/30 ,  C07K16/46

CPC classification number: C07K16/00 ,  A61K47/50 ,  A61K49/0004 ,  B82Y5/00 ,  B82Y10/00 ,  B82Y30/00 ,  C07K2317/626 ,  C07K2318/20

Abstract: The present invention concerns methods and compositions for stably tethered structures of defined compositions with multiple functionalities and/or binding specificities. Particular embodiments concern stably tethered structures comprising a homodimer of a first monomer, comprising a dimerization and docking domain attached to a first precursor, and a second monomer comprising an anchoring domain attached to a second precursor. The first and second precursors may be virtually any molecule or structure, such as antibodies, antibody fragments, antibody analogs or mimetics, aptamers, binding peptides, fragments of binding proteins, known ligands for proteins or other molecules, enzymes, detectable labels or tags, therapeutic agents, toxins, pharmaceuticals, cytokines, interleukins, interferons, radioisotopes, proteins, peptides, peptide mimetics, polynucleotides, RNAi, oligosaccharides, natural or synthetic polymeric substances, nanoparticles, quantum dots, organic or inorganic compounds, etc. The disclosed methods and compositions provide a simple, easy to purify way to obtain any binary compound attached to any monomeric compound, or any trinary compound.

Abstract translation: 本发明涉及用于具有多种功能和/或结合特异性的限定组合物的稳定束缚结构的方法和组合物。 具体实施方案涉及稳定的包含第一单体的同二聚体的束缚结构，其包含连接到第一前体的二聚化和对接结构域，以及包含连接到第二前体的锚定结构域的第二单体。 第一和第二前体实际上可以是任何分子或结构，例如抗体，抗体片段，抗体类似物或模拟物，适体，结合肽，结合蛋白片段，蛋白质或其他分子的已知配体，酶，可检测标签或标签， 治疗剂，毒素，药物，细胞因子，白介素，干扰素，放射性同位素，蛋白质，肽，肽模拟物，多核苷酸，RNAi，寡糖，天然或合成聚合物质，纳米颗粒，量子点，有机或无机化合物等。 组合物提供了一种简单，易于纯化的方式来获得连接到任何单体化合物或任何三元化合物上的任何二元化合物。

公开(公告)号：WO2007134037A2

公开(公告)日：2007-11-22

申请号：PCT/US2007/068449

申请日：2007-05-08

Applicant: IMMUNONOMEDICS, INC. ,  GOLDENBERG, David, M. ,  CHANG, Chien, Hsing ,  ROSSI, Edmund, A. ,  MCBRIDE, William, J.

Inventor： GOLDENBERG, David, M. ,  CHANG, Chien, Hsing ,  ROSSI, Edmund, A. ,  MCBRIDE, William, J.

IPC: H04M3/42

CPC classification number: A61K39/39583 ,  A61K31/4745 ,  A61K31/513 ,  A61K39/42 ,  A61K47/6809 ,  A61K47/6841 ,  A61K47/6879 ,  A61K2039/505 ,  C07K16/1045 ,  C07K16/1063 ,  C07K2317/732 ,  C07K2317/76

Abstract: The present invention concerns methods and compositions for treatment of HIV infection in a subject. The compositions may comprise a targeting molecule against an HIV antigen, such as an anti-HIV antibody or antibody fragment. The anti-HIV antibody or fragment may be conjugated to a variety of cytotoxic agents, such as doxorubicin. In a preferred embodiment, the antibody or fragment is P4/D10. Other embodiments may concern methods of imaging, detection or diagnosis of HIV infection in a subject using an anti-HIV antibody or fragment conjugated to a diagnostic agent. In alternative embodiments, a bispecific antibody with at least one binding site for an HIV antigen and at least one binding site for a carrier molecule may be administered, optionally followed by a clearing agent, followed by administration of a carrier molecule conjugated to a therapeutic agent.

Abstract translation: 本发明涉及用于治疗受试者的HIV感染的方法和组合物。 组合物可以包含针对HIV抗原的靶向分子，例如抗HIV抗体或抗体片段。 抗HIV抗体或片段可以与各种细胞毒剂如多柔比星缀合。 在优选的实施方案中，抗体或片段是P4 / D10。 其他实施方案可涉及使用抗HIV抗体或缀合至诊断剂的片段在受试者中成像，检测或诊断HIV感染的方法。 在替代实施方案中，可以施用具有HIV抗原的至少一个结合位点和载体分子的至少一个结合位点的双特异性抗体，任选地随后是清除剂，然后施用与治疗剂缀合的载体分子 。

公开(公告)号：WO2007027385A3

公开(公告)日：2007-07-12

申请号：PCT/US2006030992

申请日：2006-08-08

Applicant: IMMUNOMEDICS INC ,  MCBRIDE WILLIAM J ,  NOREN CARL

Inventor： MCBRIDE WILLIAM J ,  NOREN CARL

IPC: A61K51/00 ,  A61M36/14

CPC classification number: A61K51/088 ,  C07B59/008 ,  C07K1/13 ,  C07K14/375

Abstract: F-18 radiolabeled peptides are prepared by reacting a peptide comprising a hydroxylamine, a thiosemicarbazide, a hydrazine or a free amine group with 4-[18F]Fluorobenzaldehyde. Specific, non-limiting examples of F-18 radiolabeled peptides are described herein. The labeled peptides are useful, for example, in clinical positron emission tomography.

Abstract translation: 通过使包含羟胺，氨基硫脲，肼或游离胺基团的肽与4- [18 F]氟苯甲醛反应来制备F-18放射性标记的肽。 本文描述了F-18放射性标记肽的具体非限制性实例。 标记的肽可用于例如临床正电子发射断层摄影术。

公开(公告)号：WO2006107617A2

公开(公告)日：2006-10-12

申请号：PCT/US2006/010762

申请日：2006-03-24

Applicant: IBC PHARMACEUTICALS, INC. ,  CHIEN, Hsing, Chang ,  GOLDENBERG, David, M. ,  MCBRIDE, William, J. ,  ROSSI, Edmund, A.

Inventor： CHIEN, Hsing, Chang ,  GOLDENBERG, David, M. ,  MCBRIDE, William, J. ,  ROSSI, Edmund, A.

IPC: C07K16/46 ,  A61K39/395

CPC classification number: C07K16/18 ,  A61K39/395 ,  A61K47/65 ,  A61K47/6853 ,  A61K51/088 ,  A61K51/1048 ,  B82Y5/00 ,  B82Y10/00 ,  B82Y30/00 ,  C07K16/283 ,  C07K16/3007 ,  C07K16/468 ,  C07K2317/31 ,  C07K2317/55 ,  C07K2317/569 ,  C07K2319/00 ,  C07K2319/70

Abstract: The present invention concerns methods and compositions for stably tethered structures of defined compositions, which may have multiple functionalities and/or binding specificities. Particular embodiments concern homodimers comprising monomers that contain a dimerization and docking domain attached to a precursor. The precursors may be virtually any molecule or structure, such as antibodies, antibody fragments, antibody analogs or mimetics, aptamers, binding peptides, fragments of binding proteins, known ligands for proteins or other molecules, enzymes, detectable labels or tags, therapeutic agents, toxins, pharmaceuticals, cytokines, interleukins, interferons, radioisotopes, proteins, peptides, peptide mimetics, polynucleotides, RNAi, oligosaccharides, natural or synthetic polymeric substances, nanoparticles, quantum dots, organic or inorganic compounds, etc. Other embodiments concern tetramers comprising a first and second homodimer, which may be identical or different. The disclosed methods and compositions provide a facile and general way to obtain homodimers, homotetramers and heterotetramers of virtually any functionality and/or binding specificity.

Abstract translation: 本发明涉及可以具有多种功能和/或结合特异性的限定组合物的稳定的束缚结构的方法和组合物。 具体实施方案涉及包含单体的同型二聚体，其含有连接到前体的二聚化和对接结构域。 前体实际上可以是任何分子或结构，例如抗体，抗体片段，抗体类似物或模拟物，适体，结合肽，结合蛋白的片段，蛋白质或其他分子的已知配体，酶，可检测标记或标签，治疗剂， 毒素，药物，细胞因子，白细胞介素，干扰素，放射性同位素，蛋白质，肽，肽模拟物，多核苷酸，RNAi，寡糖，天然或合成聚合物质，纳米粒子，量子点，有机或无机化合物等。其他实施方案涉及四聚体， 和第二同二聚体，其可以相同或不同。 所公开的方法和组合物提供了实现任何功能和/或结合特异性的同源二聚体，同源四聚体和异源四聚体的简便和一般的方式。

公开(公告)号：WO2005021494A2

公开(公告)日：2005-03-10

申请号：PCT/US2004018646

申请日：2004-06-14

Applicant: IMMUNOMEDICS INC ,  MCBRIDE WILLIAM J ,  GOLDENBERG DAVID M

Inventor： MCBRIDE WILLIAM J ,  GOLDENBERG DAVID M

IPC: A61K38/00 ,  A61K49/00 ,  C07K5/10 ,  C07D

CPC classification number: C07K5/0815 ,  A61K38/00 ,  A61K47/6897 ,  A61K49/0002 ,  A61K51/109 ,  B82Y5/00 ,  C07K5/1008 ,  C07K5/1016 ,  C07K5/1019 ,  C07K5/1021 ,  C07K7/06

Abstract: The present invention provides compounds of the formula X-R1-D-[Dpr, Orn or Lys](A)-R2(Z)-D-[Dpr, Orn or Lys](B)-R3(Y)-NR4R5; or R1(X)-D-[Dpr, Orn or Lys](A)-R2(Z)-D-[Dpr, Orn or Lys](B)-R3(Y)-NR4R5, in which X is a hard acid cation chelator, a soft acid cation chelator or Ac-, R1, R2 and R3 are independently selected from a covalent bond or one or more D-amino acids that can be the same or different, Y is a hard acid cation chelator, a soft acid cation chelator or absent, Z is a hard acid cation chelator, a soft acid cation chelator or absent, and A and B are haptens or hard acid cation chelators and can be the same or different, and R4 and R5 are independently selected from the group consisting of hard acid cation chelators, soft acid cation chelators, enzymes, therapeutic agents, diagnostic agents and H. The present invention also provides methods of using these compounds and kits containing the compounds.

Abstract translation: 本发明提供式X-R1-D- [Dpr，Orn或Lys]（A）-R2（Z）-D- [Dpr，Orn或Lys]（B）-R3（Y）-NR4R5的化合物; 或R 1（X）-D- [Dpr，Orn或Lys]（A）-R2（Z）-D- [Dpr，Orn或Lys]（B）-R3（Y）-NR4R5，其中X为硬 酸阳离子螯合剂，软酸阳离子螯合剂或Ac-，R1，R2和R3独立地选自共价键或一个或多个可以相同或不同的D-氨基酸，Y是硬酸阳离子螯合剂， 软酸阳离子螯合剂或不存在，Z是硬酸阳离子螯合剂，软酸阳离子螯合剂或不存在，A和B是半抗原或硬酸阳离子螯合剂，可以相同或不同，并且R 4和R 5独立地选自 由硬酸阳离子螯合剂，软酸阳离子螯合剂，酶，治疗剂，诊断剂和H组成的组。本发明还提供使用这些化合物和含有该化合物的试剂盒的方法。

公开(公告)号：WO2004094613A2

公开(公告)日：2004-11-04

申请号：PCT/US2004/012662

申请日：2004-04-22

Applicant: IBC PHARMACEUTICALS ,  IMMUNOMEDICS, INC ,  ROSSI, Edmund, A. ,  CHANG, Chien-Hsing ,  MCBRIDE, William, J.

Inventor： ROSSI, Edmund, A. ,  CHANG, Chien-Hsing ,  MCBRIDE, William, J.

IPC: C12N

CPC classification number: C07K16/44 ,  A61K2039/505 ,  C07K16/3007 ,  C07K16/468 ,  C07K2317/24 ,  C07K2317/626 ,  C07K2318/20 ,  C07K2319/00

Abstract: The invention provides for a polyvalent protein complex (PPC) comprising two polypeptide chains generally arranged laterally to one another. Each polypeptide chain typically comprises 3 or 4 "v-regions", which comprise amino acid sequences capable of forming an antigen binding site when matched with a corresponding v-region on the opposite polypeptide chain. Up to about 6 "v-regions" can be used on each polypeptide, chain. The v-regions of each polypeptide chain are connected linearly to one another and may be connected by interspersed linking regions. When arranged in the form of the PPC, the v-regions on each polypeptide chain form individual antigen binding sites.

Abstract translation: 本发明提供了一种多价蛋白复合物（PPC），其包含通常横向彼此排列的两条多肽链。 每个多肽链通常包含3或4个“v区”，其包含当与相对的多肽链上的相应v-区域匹配时能够形成抗原结合位点的氨基酸序列。 每个多肽，链可以使用多达约6个“v区”。 每个多肽链的v-区域彼此线性连接并且可以通过散在的连接区域连接。 当以PPC的形式排列时，每个多肽链上的v-区域形成单独的抗原结合位点。

公开(公告)号：WO2002082041A2

公开(公告)日：2002-10-17

申请号：PCT/US2002/010235

申请日：2002-04-03

Applicant: IMMUNOMEDICS, INC. ,  HANSEN, Hans, J. ,  GRIFFITHS, Gary, L. ,  LEUNG, Shui-on ,  MCBRIDE, William, J. ,  QU, Zhengxing ,  GOLDENBERG, David, M.

Inventor： HANSEN, Hans, J. ,  GRIFFITHS, Gary, L. ,  LEUNG, Shui-on ,  MCBRIDE, William, J. ,  QU, Zhengxing ,  GOLDENBERG, David, M.

IPC: G01N

CPC classification number: C07K16/468 ,  A61K47/6863 ,  A61K47/6899 ,  A61K51/1048 ,  A61K51/1063 ,  A61K2039/505 ,  B82Y5/00 ,  C07K16/18 ,  C07K16/30 ,  C07K16/3007 ,  C07K16/3046 ,  C07K16/44 ,  C07K2317/12 ,  C07K2317/13 ,  C07K2317/24 ,  C07K2317/31 ,  C07K2317/55 ,  C07K2317/622 ,  C07K2319/00

Abstract: The present invention relates to a bi-specific antibody or antibody fragment having at least one arm that is reactive against a targeted tissue and at least one other arm that is reactive against a linker moiety. The linker moiety encompasses a hapten to which antibodies have been prepared. The antigenic linker is conjugated to one or more therapeutic or diagnostic agents or enzymes. The invention provides constructs and methods for producing the bi-specific antibodies or antibody fragments, as well as methods for using them.

Abstract translation: 本发明涉及一种双特异性抗体或抗体片段，其具有至少一个对靶组织有反应性的臂，以及至少一个对接头部分具有反应性的其它臂。 接头部分包括已经制备抗体的半抗原。 抗原性接头与一种或多种治疗剂或诊断剂或酶缀合。 本发明提供用于产生双特异性抗体或抗体片段的构建体和方法，以及使用它们的方法。