公开(公告)号：US09963516B2

公开(公告)日：2018-05-08

申请号：US15592871

申请日：2017-05-11

Applicant: Immunomedics, Inc.

Inventor： Li Zeng ,  Rohini Mitra ,  Edmund A. Rossi ,  Hans J. Hansen ,  David M. Goldenberg

IPC: C07K16/30 ,  C07K16/28 ,  A61K51/08 ,  A61K51/10 ,  A61K39/00

CPC classification number: C07K16/3092 ,  A61K9/0019 ,  A61K9/08 ,  A61K39/3955 ,  A61K39/39591 ,  A61K45/06 ,  A61K47/48369 ,  A61K47/48561 ,  A61K47/48638 ,  A61K47/48676 ,  A61K47/48746 ,  A61K47/6849 ,  A61K47/6869 ,  A61K47/6879 ,  A61K47/6897 ,  A61K51/088 ,  A61K51/1027 ,  A61K51/1045 ,  A61K2039/505 ,  A61K2039/54 ,  A61K2039/545 ,  A61K2039/55505 ,  A61K2039/55511 ,  B82Y5/00 ,  C07K16/065 ,  C07K16/2803 ,  C07K16/2833 ,  C07K16/2851 ,  C07K16/2887 ,  C07K16/2896 ,  C07K16/30 ,  C07K16/3007 ,  C07K16/3069 ,  C07K2317/24 ,  C07K2317/31 ,  C07K2317/51 ,  C07K2317/515 ,  C07K2317/52 ,  C07K2317/56 ,  C07K2317/94

Abstract: Disclosed are methods, compositions and uses of high concentration antibody or immunoglobulin formulations for subcutaneous, intramuscular, transdermal or other local (regional) administration, in a volume of than 3, less than 2 or less than 1 ml. Preferably, the formulation contains a high concentration formulation (HCF) buffer comprising phosphate, citrate, polysorbate 80 and mannitol at a pH of about 5.2. The formulation more preferably comprises at least 100, 150, 200, 250 mg/ml or 300 mg/ml of antibody. The methods for preparing the high concentration formulation include ultrafiltration and diafiltration to concentrate the antibody and exchange the medium for HCF buffer. Other embodiments concern use of non-G1m1 (nG1m1) allotype antibodies, such as G1m3 and/or a nG1m1,2 antibodies. The nG1m1 antibodies show decreased immunogenicity compared to G1m1 antibodies.

公开(公告)号：US09683050B2

公开(公告)日：2017-06-20

申请号：US14876200

申请日：2015-10-06

Applicant: Immunomedics, Inc.

Inventor： Li Zeng ,  Rohini Mitra ,  Edmund A. Rossi ,  Hans J. Hansen ,  David M. Goldenberg

IPC: A61K39/395 ,  C07K16/30 ,  A61K47/48 ,  C07K16/28 ,  A61K9/08 ,  A61K9/00

CPC classification number: C07K16/3092 ,  A61K9/0019 ,  A61K9/08 ,  A61K39/3955 ,  A61K39/39591 ,  A61K45/06 ,  A61K47/48369 ,  A61K47/48561 ,  A61K47/48638 ,  A61K47/48676 ,  A61K47/48746 ,  A61K47/6849 ,  A61K47/6869 ,  A61K47/6879 ,  A61K47/6897 ,  A61K51/088 ,  A61K51/1027 ,  A61K51/1045 ,  A61K2039/505 ,  A61K2039/54 ,  A61K2039/545 ,  A61K2039/55505 ,  A61K2039/55511 ,  B82Y5/00 ,  C07K16/065 ,  C07K16/2803 ,  C07K16/2833 ,  C07K16/2851 ,  C07K16/2887 ,  C07K16/2896 ,  C07K16/30 ,  C07K16/3007 ,  C07K16/3069 ,  C07K2317/24 ,  C07K2317/31 ,  C07K2317/51 ,  C07K2317/515 ,  C07K2317/52 ,  C07K2317/56 ,  C07K2317/94

Abstract: Disclosed are methods, compositions and uses of high concentration antibody or immunoglobulin formulations for subcutaneous, intramuscular, transdermal or other local (regional) administration, in a volume of than 3, less than 2 or less than 1 ml. Preferably, the formulation contains a high concentration formulation (HCF) buffer comprising phosphate, citrate, polysorbate 80 and mannitol at a pH of about 5.2. The formulation more preferably comprises at least 100, 150, 200, 250 mg/ml or 300 mg/ml of antibody. The methods for preparing the high concentration formulation include ultrafiltration and diafiltration to concentrate the antibody and exchange the medium for HCF buffer. Other embodiments concern use of non-G1m1 (nG1m1) allotype antibodies, such as G1m3 and/or a nG1m1,2 antibodies. The nG1m1 antibodies show decreased immunogenicity compared to G1m1 antibodies.

公开(公告)号：US20150165076A1

公开(公告)日：2015-06-18

申请号：US14632480

申请日：2015-02-26

Applicant: Immunomedics, Inc.

Inventor： Donglin Liu ,  David V. Gold ,  Chien-Hsing Chang ,  Serengulam V. Govindan ,  David M. Goldenberg

IPC: A61K51/10 ,  A61K49/00 ,  A61K49/04 ,  A61B8/08 ,  G01N33/574 ,  A61B6/03 ,  A61B5/055 ,  C07K16/44 ,  A61K49/16

CPC classification number: C07K16/18 ,  A61B5/055 ,  A61B6/037 ,  A61B8/481 ,  A61K31/404 ,  A61K31/519 ,  A61K31/5377 ,  A61K31/7068 ,  A61K33/24 ,  A61K38/19 ,  A61K38/193 ,  A61K38/20 ,  A61K38/21 ,  A61K38/212 ,  A61K38/215 ,  A61K38/217 ,  A61K38/28 ,  A61K38/29 ,  A61K39/39558 ,  A61K45/06 ,  A61K47/486 ,  A61K47/48746 ,  A61K47/6859 ,  A61K47/6897 ,  A61K49/0058 ,  A61K49/04 ,  A61K49/16 ,  A61K51/0406 ,  A61K51/0491 ,  A61K51/08 ,  A61K51/088 ,  A61K51/1057 ,  A61K51/1081 ,  A61K51/109 ,  A61K51/1093 ,  A61K2039/505 ,  A61K2039/507 ,  A61K2300/00 ,  B82Y5/00 ,  B82Y15/00 ,  C07K16/303 ,  C07K16/3092 ,  C07K16/44 ,  C07K2317/21 ,  C07K2317/24 ,  C07K2317/31 ,  C07K2317/34 ,  C07K2317/54 ,  C07K2317/55 ,  C07K2317/565 ,  C07K2317/567 ,  G01N33/57438 ,  G01N2333/4725

Abstract: Described herein are compositions and methods of use of anti-pancreatic cancer antibodies or fragments thereof, such as murine, chimeric, humanized or human PAM4 antibodies. The antibodies show novel and useful diagnostic characteristics, such as binding with high specificity to pancreatic and other cancers, but not to normal or benign pancreatic tissues and binding to a high percentage of early stage pancreatic cancers. Preferably, the antibodies bind to an epitope located within the second to fourth cysteine-rich domains of MUC5ac (amino acid residues 1575-2052) and are of use for the detection and diagnosis of early stage pancreatic cancer. In more preferred embodiments, the anti-pancreatic cancer antibodies can be used for immunoassay of serum samples, wherein the immunoassay detects a marker for early stage pancreatic cancer in serum. Most preferably, the serum is extracted with an organic phase, such as butanol, before immunoassay.

Abstract translation: 本文描述了使用抗胰腺癌抗体或其片段的组合物和方法，例如鼠，嵌合，人源化或人PAM4抗体。 抗体显示出新的和有用的诊断特征，例如对胰腺癌和其他癌症具有高特异性结合，但不对正常或良性胰腺组织结合并结合高百分比的早期胰腺癌。 优选地，抗体结合位于MUC5ac的第二至第四半胱氨酸富集结构域（氨基酸残基1575-2052）内的表位，并且可用于早期胰腺癌的检测和诊断。 在更优选的实施方案中，抗胰腺癌抗体可用于血清样品的免疫测定，其中免疫测定检测血清中早期胰腺癌的标志物。 最优选地，在免疫测定之前，用有机相如丁醇萃取血清。

公开(公告)号：US20140377177A1

公开(公告)日：2014-12-25

申请号：US14273163

申请日：2014-05-08

Applicant: Immunomedics, Inc.

Inventor： Christopher A. D'Souza ,  William J. McBride ,  David M. Goldenberg

IPC: A61K51/08 ,  A61K51/04

CPC classification number: A61K51/08 ,  A61B5/055 ,  A61K47/48746 ,  A61K47/6897 ,  A61K49/06 ,  A61K51/0406 ,  A61K51/041 ,  A61K51/044 ,  A61K51/0482 ,  A61K51/0491 ,  A61K51/082 ,  A61K51/083 ,  A61K51/088 ,  A61K51/109 ,  B82Y5/00 ,  C07D225/00 ,  C07F13/005

Abstract: The present application discloses compositions and methods of synthesis and use of 18F or 19F-labeled molecules of use in PET, SPECT and/or MR imaging. Preferably, the 18F or 19F 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 18F or 19F 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：US08883162B2

公开(公告)日：2014-11-11

申请号：US13688812

申请日：2012-11-29

Applicant: IBC Pharmaceuticals, Inc.

Inventor： Chien-Hsing Chang ,  David M. Goldenberg

IPC: A61K39/395 ,  A61K39/44 ,  C07K16/30 ,  A61P35/02 ,  A61P35/00 ,  A61K51/08 ,  B82Y5/00 ,  C07K16/46 ,  A61K47/48 ,  C07K16/28 ,  B82Y10/00

CPC classification number: A61K39/39558 ,  A61K47/48746 ,  A61K47/6897 ,  A61K51/088 ,  B82Y5/00 ,  B82Y10/00 ,  C07K16/2863 ,  C07K16/30 ,  C07K16/3007 ,  C07K16/468 ,  C07K2317/24 ,  C07K2317/35 ,  C07K2317/522 ,  C07K2317/526 ,  C07K2317/53 ,  C07K2317/55 ,  C07K2317/64 ,  C07K2317/73 ,  C07K2317/77 ,  C07K2317/92 ,  C07K2319/00 ,  C07K2319/30 ,  C07K2319/70 ,  A61K2300/00

Abstract: The present invention concerns methods and compositions comprising an anti-IGF-1R antibody or fragment thereof for treatment of cancer or autoimmune disease. Preferably, the cancer is renal cell carcinoma, breast cancer or pancreatic cancer. The anti-IGF-1R antibody or fragment may be part of a complex, such as a DOCK-AND-LOCK™ (DNL™) complex. Preferably, the DNL™ complex also comprises a second antibody, a second antibody fragment, an affibody or a cytokine. More preferably, the cytokine is interferon-α2b. Most preferably, the second antibody, second fragment or affibody binds to IGF-1R, TROP2 or CEACAM6. The anti-IGF-1R antibody or complex may be administered alone or in combination with a therapeutic agent, such as an mTOR inhibitor.

Abstract translation: 本发明涉及包含用于治疗癌症或自身免疫性疾病的抗IGF-1R抗体或其片段的方法和组合物。 优选地，癌症是肾细胞癌，乳腺癌或胰腺癌。 抗IGF-1R抗体或片段可以是复合物的一部分，例如DOCK-AND-LOCK TM（DNL TM）复合物。 优选地，DNL TM复合物还包含第二抗体，第二抗体片段，亲和体或细胞因子。 更优选地，细胞因子是干扰素-α2b。 最优选地，第二抗体，第二片段或亲和体结合IGF-1R，TROP2或CEACAM6。 抗IGF-1R抗体或复合物可以单独施用或与治疗剂如mTOR抑制剂组合施用。

公开(公告)号：US20140271687A1

公开(公告)日：2014-09-18

申请号：US13838667

申请日：2013-03-15

Applicant: Imre KOVESDI ,  Tibor BAKÁCS ,  Miklós SZABÓ

Inventor： Imre KOVESDI ,  Tibor BAKÁCS ,  Miklós SZABÓ

IPC: A61K47/48

CPC classification number: A61K47/48746 ,  A61K47/48615 ,  A61K47/4863 ,  A61K47/48638 ,  A61K47/48753 ,  A61K47/6863 ,  A61K47/6867 ,  A61K47/6869 ,  A61K47/6898

Abstract: The invention provides a method of targeting T-cells to tumor cells using a tumor-associated antigen (TAA) specific antibody and a T-cell specific antibody, wherein the two antibodies can bind to each other through a high affinity avidin/biotin or streptavidin/biotin connection. The invention further provides methods to target activated T-cells to different tumor types by using a T-cell specific antibody that is specific to an activated T-cell surface molecule like CTLA-4.

Abstract translation: 本发明提供了使用肿瘤相关抗原（TAA）特异性抗体和T细胞特异性抗体将T细胞靶向肿瘤细胞的方法，其中两种抗体可以通过高亲和素亲和素/生物素或链霉抗生物素蛋白 /生物素连接。 本发明还提供了通过使用对活化的T细胞表面分子如CTLA-4特异性的T细胞特异性抗体来将活化的T细胞靶向不同肿瘤类型的方法。

公开(公告)号：US08758726B2

公开(公告)日：2014-06-24

申请号：US14012582

申请日：2013-08-28

Applicant: Immunomedics, Inc.

Inventor： Christopher A. D'Souza ,  William J. McBride ,  David M. Goldenberg

IPC: A61B5/055 ,  A61K51/04 ,  A61K49/06 ,  C07F13/00 ,  C07D225/00

CPC classification number: A61K51/08 ,  A61B5/055 ,  A61K47/48746 ,  A61K47/6897 ,  A61K49/06 ,  A61K51/0406 ,  A61K51/041 ,  A61K51/044 ,  A61K51/0482 ,  A61K51/0491 ,  A61K51/082 ,  A61K51/083 ,  A61K51/088 ,  A61K51/109 ,  B82Y5/00 ,  C07D225/00 ,  C07F13/005

Abstract: The present application discloses compositions and methods of synthesis and use of 18F or 19F-labeled molecules of use in PET, SPECT and/or MR imaging. Preferably, the 18F or 19F 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 18F or 19F 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.

Abstract translation: 本申请公开了在PET，SPECT和/或MR成像中合成和使用18F或19F标记的分子的组合物和方法。 优选地，18F或19F通过与IIIA族金属形成络合物并将该复合物与双功能螯合剂结合（其可以直接或间接连接到靶向分子）而与靶向分子缀合。 在其它实施方案中，18F或19F标记的部分可以包含与靶向疾病相关抗原的双特异性抗体组合使用的可靶向构建体。 所公开的方法和组合物允许在30分钟或更短时间内非常高的效率和比活性的分子的简单且可重现的标记。 在优选的实施方案中，标记的分子可以在标记后不经纯化用于受试者的成像。

公开(公告)号：US20130309177A1

公开(公告)日：2013-11-21

申请号：US13918236

申请日：2013-06-14

Applicant: Immunomedics, Inc.

Inventor： William J. McBride ,  Christopher A. D'Souza ,  David M. Goldenberg

IPC: A61K49/16

CPC classification number: A61K51/1045 ,  A61K47/48746 ,  A61K47/6897 ,  A61K49/0002 ,  A61K49/16 ,  A61K51/0406 ,  A61K51/0474 ,  A61K51/0482 ,  A61K51/0491 ,  A61K51/08 ,  A61K51/082 ,  A61K51/083 ,  A61K51/088 ,  A61K51/109 ,  B82Y5/00

Abstract: The present application discloses compositions and methods of synthesis and use involving click chemistry reactions for in vivo or in vitro formation of therapeutic and/or diagnostic complexes. Preferably, the diagnostic complex is of use for 18F imaging, while the therapeutic complex is of use for targeted delivery of chemotherapeutic drugs or toxins. More preferably, a chelating moiety or targetable construct may be conjugated to a targeting molecule, such as an antibody or antibody fragment, using a click chemistry reaction involving cyclooctyne, nitrone or azide reactive moieties. In most preferred embodiments, the click chemistry reaction occurs in vivo. In vivo click chemistry is not limited to 18F labeling but can be used for delivering a variety of therapeutic and/or diagnostic agents.

公开(公告)号：US08496912B2

公开(公告)日：2013-07-30

申请号：US13752877

申请日：2013-01-29

Applicant: Immunomedics, Inc.

Inventor： William J. McBride ,  Christopher A. D'Souza ,  David M. Goldenberg

IPC: A61K49/04

CPC classification number: A61K51/1045 ,  A61K47/48746 ,  A61K47/6897 ,  A61K49/0002 ,  A61K49/16 ,  A61K51/0406 ,  A61K51/0474 ,  A61K51/0482 ,  A61K51/0491 ,  A61K51/08 ,  A61K51/082 ,  A61K51/083 ,  A61K51/088 ,  A61K51/109 ,  B82Y5/00

Abstract: The present application discloses compositions and methods of synthesis and use involving click chemistry reactions for in vivo or in vitro formation of therapeutic and/or diagnostic complexes. Preferably, the diagnostic complex is of use for 18F imaging, while the therapeutic complex is of use for targeted delivery of chemotherapeutic drugs or toxins. More preferably, a chelating moiety or targetable construct may be conjugated to a targeting molecule, such as an antibody or antibody fragment, using a click chemistry reaction involving cyclooctyne, nitrone or azide reactive moieties. In most preferred embodiments, the click chemistry reaction occurs in vivo. In vivo click chemistry is not limited to 18F labeling but can be used for delivering a variety of therapeutic and/or diagnostic agents.

公开(公告)号：US20130095033A1

公开(公告)日：2013-04-18

申请号：US13688812

申请日：2012-11-29

Applicant: IBC Pharmaceuticals, Inc.

Inventor： Chien-Hsing Chang ,  David M. Goldenberg

IPC: A61K39/395

CPC classification number: A61K39/39558 ,  A61K47/48746 ,  A61K47/6897 ,  A61K51/088 ,  B82Y5/00 ,  B82Y10/00 ,  C07K16/2863 ,  C07K16/30 ,  C07K16/3007 ,  C07K16/468 ,  C07K2317/24 ,  C07K2317/35 ,  C07K2317/522 ,  C07K2317/526 ,  C07K2317/53 ,  C07K2317/55 ,  C07K2317/64 ,  C07K2317/73 ,  C07K2317/77 ,  C07K2317/92 ,  C07K2319/00 ,  C07K2319/30 ,  C07K2319/70 ,  A61K2300/00

Abstract: The present invention concerns methods and compositions comprising an anti-IGF-1R antibody or fragment thereof for treatment of cancer or autoimmune disease. Preferably, the cancer is renal cell carcinoma, breast cancer or pancreatic cancer. The anti-IGF-1R antibody or fragment may be part of a complex, such as a DOCK-AND-LOCK™ (DNL™) complex. Preferably, the DNL™ complex also comprises a second antibody, a second antibody fragment, an affibody or a cytokine. More preferably, the cytokine is interferon-α2b. Most preferably, the second antibody, second fragment or affibody binds to IGF-1R, TROP2 or CEACAM6. The anti-IGF-1R antibody or complex may be administered alone or in combination with a therapeutic agent, such as an mTOR inhibitor.

Abstract translation: 本发明涉及包含用于治疗癌症或自身免疫性疾病的抗IGF-1R抗体或其片段的方法和组合物。 优选地，癌症是肾细胞癌，乳腺癌或胰腺癌。 抗IGF-1R抗体或片段可以是复合物的一部分，例如DOCK-AND-LOCK TM（DNL TM）（DNL TM）复合物。 优选地，DNL TM复合物还包含第二抗体，第二抗体片段，亲和体或细胞因子。 更优选地，细胞因子是干扰素-α2b。 最优选地，第二抗体，第二片段或亲和体结合IGF-1R，TROP2或CEACAM6。 抗IGF-1R抗体或复合物可以单独施用或与治疗剂如mTOR抑制剂组合施用。