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：US10022427B2

公开(公告)日：2018-07-17

申请号：US14997843

申请日：2016-01-18

Applicant: IBC Pharmaceuticals, Inc.

Inventor： Chien-Hsing Chang ,  David M. Goldenberg ,  Donglin Liu

IPC: A61K38/21 ,  A61K39/00 ,  A61K39/395 ,  A61K47/68 ,  C07K14/555 ,  C07K16/22 ,  C07K16/30 ,  C07K16/40 ,  C07K16/46 ,  C07K16/28 ,  A61K47/48 ,  C07K16/00 ,  G01N33/68 ,  A61K45/06 ,  A61K9/00 ,  C07K16/18 ,  C07K16/44 ,  B82Y30/00

Abstract: The present invention concerns methods and compositions for forming complexes of interferon-λ with an antibody or antigen-binding antibody fragment. In preferred embodiments, the interferon-λ and the antibody or fragment are fusion proteins, each comprising a dimerization and docking domain (DDD) moiety from human protein kinase A or an anchor domain (AD) moiety from an A-kinase anchoring protein (AKAP). In more preferred embodiments, the interferon-antibody complex is more efficacious for treatment of cancer, asthma, Alzheimer's disease, multiple sclerosis or viral infection than interferon-λ alone, antibody alone, or the combination of unconjugated interferon-λ and antibody.

公开(公告)号：US09862770B2

公开(公告)日：2018-01-09

申请号：US14505595

申请日：2014-10-03

Applicant: IBC Pharmaceuticals, Inc.

Inventor： Chien-Hsing Chang ,  David M. Goldenberg

IPC: C07K16/30 ,  C07K17/06 ,  C07K16/46 ,  C07K16/28 ,  A61K51/10 ,  A61K47/68 ,  A61K39/00

CPC classification number: C07K16/2863 ,  A61K47/6813 ,  A61K47/6845 ,  A61K47/6851 ,  A61K51/103 ,  A61K51/1045 ,  A61K2039/505 ,  C07K16/30 ,  C07K2317/24 ,  C07K2317/31 ,  C07K2317/35 ,  C07K2317/522 ,  C07K2317/53 ,  C07K2317/55 ,  C07K2317/565 ,  C07K2317/73 ,  C07K2317/76

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 produced by binding interaction between anchor domain moiety of A-kinase anchoring protein and dimerization and docking domain moiety of protein kinase A regulatory subunit) complex. Preferably, the DNL™ (complex produced by binding interaction between anchor domain moiety of A-kinase anchoring protein and dimerization and docking domain moiety of protein kinase A regulatory subunit) 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.

公开(公告)号：US09839689B2

公开(公告)日：2017-12-12

申请号：US14969901

申请日：2015-12-15

Applicant: IBC Pharmaceuticals, Inc.

Inventor： Chien-Hsing Chang ,  David M. Goldenberg

IPC: A61K39/395 ,  A61K31/00 ,  C07K16/10 ,  C07K19/00 ,  A61K31/704 ,  A61K47/48 ,  A61K39/00

CPC classification number: A61K39/39575 ,  A61K31/00 ,  A61K31/704 ,  A61K39/3955 ,  A61K39/42 ,  A61K39/44 ,  A61K47/60 ,  A61K47/6803 ,  A61K47/6809 ,  A61K47/6839 ,  A61K47/6879 ,  A61K2039/505 ,  C07K16/1063 ,  C07K16/2887 ,  C07K2317/35 ,  C07K2317/51 ,  C07K2317/55 ,  C07K2317/64 ,  C07K2317/73 ,  C07K2317/732 ,  C07K2317/76

Abstract: The present invention concerns methods and compositions for treatment of HIV infection in a subject, utilizing a DNL® complex comprising at least one anti-HIV therapeutic agent, attached to an antibody, antibody fragment or PEG. In a preferred embodiment, the antibody or fragment binds to an antigen selected from gp120, gp41, CD4 and CCR5. In a more preferred embodiment the antibody is P4/D10 or 2G12, although other anti-HIV antibodies are known and may be utilized. In a most preferred embodiment, the anti-HIV therapeutic agent is a fusion inhibitor, such as T20, T61, T651, T1249, T2635, CP32M or T-1444, although other anti-HIV therapeutic agents are known and may be utilized. The DNL® complex may be administered alone or may be co-administered with one or more additional anti-HIV therapeutic agents.

公开(公告)号：US20170283511A1

公开(公告)日：2017-10-05

申请号：US15620126

申请日：2017-06-12

Applicant: IBC Pharmaceuticals, Inc.

Inventor： David M. Goldenberg ,  Rongxiu Li ,  Chien-Hsing Chang

IPC: C07K16/46 ,  C07K16/24

CPC classification number: C07K16/468 ,  A61K45/06 ,  A61K47/6801 ,  A61K47/6803 ,  A61K47/6845 ,  A61K47/6889 ,  A61K2039/505 ,  C07K14/46 ,  C07K16/241 ,  C07K16/248 ,  C07K2317/24 ,  C07K2317/31 ,  C07K2317/33 ,  C07K2317/55 ,  C07K2317/565 ,  C07K2317/60 ,  C07K2317/76 ,  C07K2317/92 ,  C07K2319/00 ,  C07K2319/70

Abstract: The present invention concerns compositions and methods of use of bispecific antibodies comprising at least one anti-TNF-α antibody or antigen-binding fragment thereof and at least one anti-IL-6 antibody or antigen-binding fragment thereof. Preferably, the bispecific antibody is in the form of a DNL® complex. The anti-TNF-α or anti-IL-6 antibodies may comprise specific CDR sequences disclosed herein. The compositions and methods are of use to treat autoimmune disease, immune system dysfunction or inflammatory disease, as disclosed herein.

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.