公开(公告)号：US10183992B2

公开(公告)日：2019-01-22

申请号：US15590514

申请日：2017-05-09

Applicant: IBC Pharmaceuticals, Inc.

Inventor： Chien-Hsing Chang ,  David M. Goldenberg ,  Edmund A. Rossi ,  Diane Rossi

IPC: C07K16/28 ,  C07K16/30 ,  C07K16/18 ,  A61K38/21 ,  A61K47/42 ,  A61K39/395 ,  A61K45/06 ,  A61K38/19 ,  C07K16/40 ,  C07K16/32 ,  C07K16/44 ,  A61K9/00 ,  A61K38/17 ,  A61K38/45 ,  C07K14/47 ,  C07K16/46 ,  C07K14/00 ,  C12N9/12 ,  A61K47/60 ,  A61K47/64 ,  A61K39/00 ,  A61K38/00

Abstract: The present invention concerns compositions and methods of use of T-cell redirecting complexes, with at least one binding site for a T-cell antigen and at least one binding site for an antigen on a diseased cell or pathogen. Preferably, the complex is a DNL™ complex. More preferably, the complex comprises a bispecific antibody (bsAb). Most preferably, the bsAb is an anti-CD3×anti-CD19 bispecific antibody, although antibodies against other T-cell antigens and/or disease-associated antigens may be used. The complex is capable of targeting effector T cells to induce T-cell-mediated cytotoxicity of cells associated with a disease, such as cancer, autoimmune disease or infectious disease. The cytotoxic immune response is enhanced by co-administration of interfon-based agents that comprise interferon-α, interferon-β, interferon-λ1, interferon-λ2 or interferon-λ3.

公开(公告)号：US09737617B2

公开(公告)日：2017-08-22

申请号：US14491189

申请日：2014-09-19

Applicant: IBC Pharmaceuticals, Inc.

Inventor： Chien-Hsing Chang ,  David M. Goldenberg ,  Edmund A. Rossi

IPC: A61K47/48 ,  C07K16/28 ,  A61K51/10 ,  C07K14/47 ,  A61K39/395

CPC classification number: A61K47/6807 ,  A61K39/3955 ,  A61K47/6811 ,  A61K47/6813 ,  A61K47/6815 ,  A61K47/6849 ,  A61K47/6851 ,  A61K47/6867 ,  A61K47/6885 ,  A61K51/1027 ,  A61K51/1045 ,  C07K14/47 ,  C07K2317/31 ,  C07K2317/732 ,  C07K2317/734 ,  C07K2319/33 ,  C07K2319/70 ,  C07K2319/74

Abstract: Disclosed herein are compositions and methods of use comprising hexavalent DNL complexes. Preferably, the complexes comprise anti-CD20 and/or anti-CD22 antibodies or fragments thereof. More preferably, the anti-CD20 antibody is veltuzumab and the anti-CD22 antibody is epratuzumab. Administration of the subject hexavalent DNL complexes induces apoptosis and cell death of target cells in diseases such as B-cell lymphomas or leukemias, autoimmune disease or immune dysfunction disease. In most preferred embodiments, the DNL complexes increase levels of phosphorylated p38 and PTEN, decrease levels of phosphorylated Lyn, Akt, ERK, IKKα/β and IκBα, increase expression of RKIP and Bax and decrease expression of Mcl-1, Bcl-xL, Bcl-2, and phospho-BAD in target cells. The subject DNL complexes show EC50 values for inhibiting tumor cell growth in the low nanomolar or even sub-nanomolar concentration range.

公开(公告)号：US09670286B2

公开(公告)日：2017-06-06

申请号：US15169903

申请日：2016-06-01

Applicant: IBC Pharmaceuticals, Inc.

Inventor： Chien-Hsing Chang ,  David M. Goldenberg ,  Edmund A. Rossi ,  Diane Rossi

IPC: C07K16/28 ,  C07K16/30 ,  A61K38/21 ,  A61K47/48 ,  A61K39/395 ,  A61K31/4745 ,  A61K45/06 ,  C07K16/44 ,  A61K39/00

CPC classification number: C07K16/30 ,  A61K31/4745 ,  A61K38/21 ,  A61K38/212 ,  A61K39/3955 ,  A61K39/39558 ,  A61K45/06 ,  A61K47/60 ,  A61K47/6803 ,  A61K47/6851 ,  A61K47/6857 ,  A61K47/6859 ,  A61K47/6863 ,  A61K2039/505 ,  A61K2039/507 ,  C07K16/2803 ,  C07K16/2809 ,  C07K16/2833 ,  C07K16/2863 ,  C07K16/2887 ,  C07K16/3007 ,  C07K16/44 ,  C07K2317/24 ,  C07K2317/31 ,  C07K2317/51 ,  C07K2317/515 ,  C07K2317/54 ,  C07K2317/55 ,  C07K2317/565 ,  C07K2317/622 ,  C07K2317/73 ,  C07K2317/732 ,  C07K2317/77 ,  A61K2300/00

Abstract: The present invention concerns compositions and methods of use of bispecific antibodies comprising at least one binding site for Trop-2 (EGP-1) and at least one binding site for CD3. The bispecific antibodies are of use for inducing an immune response against a Trop-2 expressing tumor, such as carcinoma of the esophagus, pancreas, lung, stomach, colon, rectum, urinary bladder, breast, ovary, uterus, kidney or prostate. The methods may comprising administering the bispecific antibody alone, or with one or more therapeutic agents such as antibody-drug conjugates, interferons (preferably interferon-α), and/or checkpoint inhibitor antibodies. The bispecific antibody is capable of targeting effector T cells, NK cells, monocytes or neutrophils to induce leukocyte-mediated cytotoxicity of Trop-2+ cancer cells. The cytotoxic immune response is enhanced by co-administration of interferon, checkpoint inhibitor antibody and/or ADC.

公开(公告)号：US20170021017A1

公开(公告)日：2017-01-26

申请号：US15287329

申请日：2016-10-06

Applicant: IBC Pharmaceuticals, Inc.

Inventor： Chien-Hsing Chang ,  David M. Goldenberg ,  Edmund A. Rossi ,  Diane Rossi

IPC: A61K39/395 ,  C07K16/30 ,  A61K38/21 ,  C07K16/28 ,  A61K45/06 ,  A61K9/00

CPC classification number: A61K39/3955 ,  A61K9/0019 ,  A61K38/21 ,  A61K38/212 ,  A61K39/39558 ,  A61K45/06 ,  A61K47/6803 ,  A61K47/6851 ,  A61K2039/505 ,  A61K2039/507 ,  A61K2039/54 ,  C07K16/2803 ,  C07K16/2809 ,  C07K16/2833 ,  C07K16/2863 ,  C07K16/2887 ,  C07K16/30 ,  C07K16/3007 ,  C07K16/44 ,  C07K2317/31 ,  C07K2317/54 ,  C07K2317/55 ,  C07K2317/622 ,  C07K2317/73 ,  A61K2300/00

Abstract: The present invention concerns combinations of two or more agents for inducing an immune response to cancer or infectious disease. Agents may include leukocyte redirecting complexes, antibody-drug conjugates, interferons (preferably interferon-α), and/or checkpoint inhibitor antibodies. The leukocyte redirecting complexes have at least one binding site for a leukocyte antigen and at least one binding site for an antigen on a diseased cell or pathogen. Preferably, the complex is a DNL™ complex. More preferably, the complex comprises a bispecific antibody (bsAb). Most preferably, the bsAb is an anti-CD3× anti-CD19 bispecific antibody, although antibodies against other leukocyte antigens and/or disease-associated antigens may be used. The complex is capable of targeting effector T cells, NK cells, monocytes or neutrophils to induce leukocyte-mediated cytotoxicity of cells associated with cancer or infectious disease. The cytotoxic immune response is enhanced by co-administration of interferon, checkpoint inhibitor antibody and/or ADC.

Abstract translation: 本发明涉及用于诱导对癌症或感染性疾病的免疫应答的两种或更多种试剂的组合。 试剂可以包括白细胞重定向复合物，抗体 - 药物偶联物，干扰素（优选干扰素-α）和/或检查点抑制剂抗体。 白细胞重定向复合物具有白细胞抗原的至少一个结合位点和患病细胞或病原体上的抗原的至少一个结合位点。 优选地，复合物是DNL TM复合物。 更优选地，复合物包含双特异性抗体（bsAb）。 最优选地，bsAb是抗CD3×抗CD19双特异性抗体，尽管可以使用针对其它白细胞抗原和/或疾病相关抗原的抗体。 该复合物能够靶向效应T细胞，NK细胞，单核细胞或嗜中性粒细胞，以诱导与癌症或感染性疾病相关的细胞的白细胞介导的细胞毒性。 通过共同给予干扰素，检查点抑制剂抗体和/或ADC来增强细胞毒性免疫应答。

公开(公告)号：US20160375108A1

公开(公告)日：2016-12-29

申请号：US15264747

申请日：2016-09-14

Applicant: Immunomedics, Inc. ,  IBC Pharmaceuticals, Inc.

Inventor： Chien-Hsing Chang ,  David M. Goldenberg ,  Edmund A. Rossi

IPC: A61K38/46 ,  C07K16/28 ,  A61K45/06 ,  C07K16/30 ,  A61K47/48 ,  A61K39/395

CPC classification number: A61K38/465 ,  A61K39/0011 ,  A61K39/39558 ,  A61K45/06 ,  A61K47/62 ,  A61K47/646 ,  A61K47/6897 ,  A61K51/088 ,  A61K51/1027 ,  A61K2039/505 ,  A61K2039/6056 ,  A61K2039/625 ,  B82Y5/00 ,  C07K16/2803 ,  C07K16/2833 ,  C07K16/2887 ,  C07K16/30 ,  C07K16/3007 ,  C07K16/468 ,  C07K2317/24 ,  C07K2317/31 ,  C07K2317/522 ,  C07K2317/524 ,  C07K2317/526 ,  C07K2317/55 ,  C07K2317/565 ,  C07K2317/567 ,  C07K2317/622 ,  C07K2317/76 ,  C07K2317/77 ,  C07K2317/92 ,  C07K2319/00 ,  C07K2319/30 ,  C12N9/96 ,  C12Y207/11011 ,  C12Y301/27

Abstract: The present invention concerns methods and compositions for forming immunotoxin complexes having a high efficacy and low systemic toxicity. In preferred embodiments, the toxin moiety is a ranpirnase (Rap), such as Rap(Q). In more preferred embodiments, the immunotoxin is made using dock-and-lock (DNL) technology. The immunotoxin exhibits improved pharmacokinetics, with a longer serum half-life and significantly greater efficacy compared to toxin alone, antibody alone, unconjugated toxin plus antibody or even other types of toxin-antibody constructs. In a most preferred embodiment the construct comprises an anti-Trop-2 antibody conjugated to Rap, although other combinations of antibodies, antibody fragments and toxins may be used to form the subject immunotoxins. The immunotoxins are of use to treat a variety of diseases, such as cancer, autoimmune disease or immune dysfunction.

Abstract translation: 本发明涉及用于形成具有高效力和低全身毒性的免疫毒素复合物的方法和组合物。 在优选的实施方案中，毒素部分是兰普瑞酶（Rap），例如Rap（Q）。 在更优选的实施方案中，免疫毒素使用对接 - 锁（DNL）技术制备。 与单独的毒素，单独的抗体，未缀合的毒素加抗体或甚至其它类型的毒素 - 抗体构建体相比，免疫毒素表现出改进的药代动力学，具有较长的血清半衰期和显着更高的功效。 在最优选的实施方案中，构建体包含与Rap结合的抗Trop-2抗体，尽管抗体，抗体片段和毒素的其它组合可用于形成受试者免疫毒素。 免疫毒素可用于治疗各种疾病，例如癌症，自身免疫性疾病或免疫功能障碍。

公开(公告)号：US20150050715A1

公开(公告)日：2015-02-19

申请号：US14521013

申请日：2014-10-22

Applicant: IBC Pharmaceuticals, Inc.

Inventor： Chien-Hsing Chang ,  David M. Goldenberg ,  William J. McBride ,  Edmund A. Rossi

IPC: C07K16/18

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 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.

公开(公告)号：US20150037283A1

公开(公告)日：2015-02-05

申请号：US14520596

申请日：2014-10-22

Applicant: IBC Pharmaceuticals, Inc.

Inventor： Chien-Hsing Chang ,  David M. Goldenberg ,  Edmund A. Rossi

IPC: C07K16/28 ,  A61K47/48

CPC classification number: A61K39/3955 ,  A61K31/7076 ,  A61K38/212 ,  A61K39/39541 ,  A61K45/06 ,  A61K47/48384 ,  A61K47/48415 ,  A61K47/48561 ,  A61K47/48569 ,  A61K47/487 ,  A61K47/6803 ,  A61K47/6811 ,  A61K47/6849 ,  A61K47/6851 ,  A61K47/6885 ,  A61K51/1027 ,  A61K51/1045 ,  A61K2039/505 ,  C07K14/47 ,  C07K16/2803 ,  C07K16/2833 ,  C07K16/2887 ,  C07K16/2896 ,  C07K2317/31 ,  C07K2317/51 ,  C07K2317/515 ,  C07K2317/522 ,  C07K2317/524 ,  C07K2317/526 ,  C07K2317/53 ,  C07K2317/55 ,  C07K2317/565 ,  C07K2317/73 ,  C07K2317/732 ,  C07K2317/734 ,  C07K2319/30 ,  C07K2319/55 ,  C07K2319/70

Abstract: Disclosed are compositions and methods comprising combinations of anti-CD74 antibodies with a therapeutic agent that is attached to the anti-CD74 antibody or separately administered. Preferably, the therapeutic agent is an antibody that binds to an antigen different from CD74, such as CD19, CD20, CD21, CD22, CD23, CD37, CD40, CD40L, CD52, CD80, IL-6, CXCR4 or HLA-DR. However, the therapeutic agent may be an immunomodulator, a cytokine, a toxin or other known therapeutic agent. Preferably, the anti-CD74 antibody is part of a DNL complex. More preferably, combination therapy with the anti-CD74 antibody and therapeutic agent is more effective than antibody alone, therapeutic agent alone, or the combination of unconjugated anti-CD74 antibody and therapeutic agent. Administration of combination induces apoptosis of target cells in diseases in which CD74 is overexpressed, such as solid tumors, B-cell lymphomas or leukemias, autoimmune disease, immune dysfunction disease or diabetes.

Abstract translation: 公开了包含抗CD74抗体与连接于抗CD74抗体或单独施用的治疗剂的组合的组合物和方法。 优选地，治疗剂是与CD74，例如CD19，CD20，CD21，CD22，CD23，CD37，CD40，CD40L，CD52，CD80，IL-6，CXCR4或HLA-DR不同的抗原结合的抗体。 然而，治疗剂可以是免疫调节剂，细胞因子，毒素或其它已知的治疗剂。 优选地，抗CD74抗体是DNL复合物的一部分。 更优选地，与抗CD74抗体和治疗剂的组合疗法比单独的抗体，单独的治疗剂或非共轭抗CD74抗体和治疗剂的组合更有效。 组合的施用诱导CD74过表达的疾病中靶细胞的凋亡，例如实体瘤，B细胞淋巴瘤或白血病，自身免疫疾病，免疫功能障碍性疾病或糖尿病。

公开(公告)号：US20150010982A1

公开(公告)日：2015-01-08

申请号：US14488921

申请日：2014-09-17

Applicant: IBC PHARMACEUTICALS, INC.

Inventor： Chien-Hsing Chang ,  David M. Goldenberg ,  William J. McBride ,  Edmund A. Rossi

IPC: C12N9/12 ,  C07K14/475 ,  C07K16/30 ,  C07K16/28

CPC classification number: A61K47/48438 ,  A61K31/00 ,  A61K38/00 ,  A61K47/48415 ,  A61K47/48484 ,  A61K47/485 ,  A61K47/48538 ,  A61K47/48546 ,  A61K47/48561 ,  A61K47/48569 ,  A61K47/6811 ,  A61K47/6817 ,  A61K47/6829 ,  A61K47/6833 ,  A61K47/6843 ,  A61K47/6845 ,  A61K47/6849 ,  A61K47/6851 ,  A61K2039/505 ,  B82Y5/00 ,  B82Y10/00 ,  B82Y15/00 ,  C07K14/475 ,  C07K16/18 ,  C07K16/22 ,  C07K16/28 ,  C07K16/2803 ,  C07K16/2833 ,  C07K16/2851 ,  C07K16/2863 ,  C07K16/2881 ,  C07K16/2887 ,  C07K16/2896 ,  C07K16/3007 ,  C07K16/3092 ,  C07K16/32 ,  C07K2317/31 ,  C07K2317/55 ,  C07K2317/76 ,  C07K2319/30 ,  C07K2319/35 ,  C07K2319/70 ,  C07K2319/74 ,  C12N9/12 ,  C12N9/22 ,  C12N9/96 ,  C12Y207/11001 ,  G01N33/54353 ,  G01N33/588 ,  Y02A50/491

Abstract: The present invention concerns methods and compositions for making and using bioactive assemblies of defined compositions, which may have multiple functionalities and/or binding specificities. In particular embodiments, the bioactive assembly is formed using dock-and-lock (DNL) methodology, which takes advantage of the specific binding interaction between dimerization and docking domains (DDD) and anchoring domains (AD) to form the assembly. In various embodiments, one or more effectors may be attached to a DDD or AD sequence. Complementary AD or DDD sequences may be attached to an adaptor module that forms the core of the bioactive assembly, allowing formation of the assembly through the specific DDD/AD binding interactions. Such assemblies may be attached to a wide variety of effector moieties for treatment, detection and/or diagnosis of a disease, pathogen infection or other medical or veterinary condition.

公开(公告)号：US20130295005A1

公开(公告)日：2013-11-07

申请号：US13904534

申请日：2013-05-29

Applicant: IBC Pharmaceuticals, Inc.

Inventor： Chien-Hsing Chang ,  David M. Goldenberg ,  Edmund A. Rossi

IPC: A61K39/395 ,  A61K38/21

CPC classification number: A61K39/3955 ,  A61K31/7076 ,  A61K38/212 ,  A61K39/39541 ,  A61K45/06 ,  A61K47/48384 ,  A61K47/48415 ,  A61K47/48561 ,  A61K47/48569 ,  A61K47/487 ,  A61K47/6803 ,  A61K47/6811 ,  A61K47/6849 ,  A61K47/6851 ,  A61K47/6885 ,  A61K51/1027 ,  A61K51/1045 ,  A61K2039/505 ,  C07K14/47 ,  C07K16/2803 ,  C07K16/2833 ,  C07K16/2887 ,  C07K16/2896 ,  C07K2317/31 ,  C07K2317/51 ,  C07K2317/515 ,  C07K2317/522 ,  C07K2317/524 ,  C07K2317/526 ,  C07K2317/53 ,  C07K2317/55 ,  C07K2317/565 ,  C07K2317/73 ,  C07K2317/732 ,  C07K2317/734 ,  C07K2319/30 ,  C07K2319/55 ,  C07K2319/70

Abstract: Disclosed are compositions and methods comprising combinations of anti-CD74 antibodies with a therapeutic agent that is attached to the anti-CD74 antibody or separately administered. Preferably, the therapeutic agent is an antibody that binds to an antigen different from CD74, such as CD19, CD20, CD21, CD22, CD23, CD37, CD40, CD40L, CD52, CD80, IL-6, CXCR4 or HLA-DR. However, the therapeutic agent may be an immunomodulator, a cytokine, a toxin or other known therapeutic agent. Preferably, the anti-CD74 antibody is part of a DNL complex. More preferably, combination therapy with the anti-CD74 antibody and therapeutic agent is more effective than antibody alone, therapeutic agent alone, or the combination of unconjugated anti-CD74 antibody and therapeutic agent. Administration of combination induces apoptosis of target cells in diseases in which CD74 is overexpressed, such as solid tumors, B-cell lymphomas or leukemias, autoimmune disease, immune dysfunction disease or diabetes.

公开(公告)号：US10308688B2

公开(公告)日：2019-06-04

申请号：US15064128

申请日：2016-03-08

Applicant: IBC Pharmaceuticals, Inc.

Inventor： Chien-Hsing Chang ,  David M. Goldenberg ,  Edmund A. Rossi ,  Diane Rossi

IPC: A61K39/395 ,  A61K9/19 ,  C07K16/30 ,  C07K16/28 ,  A61K38/21 ,  C07K14/00 ,  C07K16/18 ,  A61K47/42 ,  A61K45/06 ,  A61K38/19 ,  C07K16/40 ,  C07K16/32 ,  C07K16/44 ,  A61K9/00 ,  A61K38/17 ,  A61K38/45 ,  C07K14/47 ,  C07K16/46 ,  C12N9/12 ,  A61K47/60 ,  A61K47/64 ,  A61K39/00 ,  A61K38/00

Abstract: The present invention concerns compositions and methods of use of T-cell redirecting complexes, with at least one binding site for a T-cell antigen and at least one binding site for an antigen on a diseased cell or pathogen. Preferably, the complex is a DNL™ complex. More preferably, the complex comprises a bispecific antibody (bsAb). Most preferably, the bsAb is an anti-CD3×anti-CD19 bispecific antibody, although antibodies against other T-cell antigens and/or disease-associated antigens may be used. The complex is capable of targeting effector T cells to induce T-cell-mediated cytotoxicity of cells associated with a disease, such as cancer, autoimmune disease or infectious disease. The cytotoxic immune response is enhanced by co-administration of interferon-based agents that comprise interferon-α, interferon-β, interferon-λ1, interferon-λ2 or interferon-λ3.