公开(公告)号：US09457100B2

公开(公告)日：2016-10-04

申请号：US13589575

申请日：2012-08-20

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

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

IPC: A61K38/18 ,  A61K47/48 ,  A61K38/19 ,  A61K38/20 ,  A61K38/21 ,  A61K51/08 ,  A61K51/10 ,  C07K14/00 ,  B82Y5/00 ,  B82Y10/00

CPC classification number: A61K47/6835 ,  A61K38/1816 ,  A61K38/193 ,  A61K38/212 ,  A61K47/60 ,  A61K47/65 ,  A61K47/6853 ,  A61K51/1048 ,  B82Y5/00 ,  B82Y10/00 ,  C07K2319/00 ,  C07K2319/70

Abstract: The present invention concerns methods and compositions for forming PEGylated complexes of defined stoichiometry and structure. In preferred embodiments, the PEGylated complex is formed using dock-and-lock technology, by attaching a target agent to a DDD sequence and attaching a PEG moiety to an AD sequence and allowing the DDD sequence to bind to the AD sequence in a 2:1 stoichiometry, to form PEGylated complexes with two target agents and one PEG moiety. In alternative embodiments, the target agent may be attached to the AD sequence and the PEG to the DDD sequence to form PEGylated complexes with two PEG moieties and one target agent. In more preferred embodiments, the target agent may comprise any peptide or protein of physiologic or therapeutic activity. The PEGylated complexes exhibit a significantly slower rate of clearance when injected into a subject and are of use for treatment of a wide variety of diseases.

Abstract translation: 本发明涉及用于形成定义化学计量和结构的聚乙二醇化配合物的方法和组合物。 在优选的实施方案中，使用对接和锁定技术形成聚乙二醇化复合物，通过将目标试剂连接到DDD序列并将PEG部分连接到AD序列并允许DDD序列以2： 1化学计量，以形成与两个靶剂和一个PEG部分的聚乙二醇化复合物。 在替代实施方案中，靶物质可以连接到AD序列，并将PEG连接到DDD序列以形成具有两个PEG部分和一个目标试剂的PEG化复合物。 在更优选的实施方案中，靶剂可以包含生理或治疗活性的任何肽或蛋白质。 当注射到受试者中时，聚乙二醇化复合物表现出明显较慢的清除率，并且可用于治疗各种各样的疾病。

公开(公告)号：US08906377B2

公开(公告)日：2014-12-09

申请号：US12968936

申请日：2010-12-15

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

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

IPC: A61K39/395 ,  C07K16/46 ,  C07K16/28 ,  C07K14/52 ,  A61K38/19 ,  C07K16/18 ,  C07K16/22 ,  C07K16/44 ,  A61K47/48 ,  A61K51/08 ,  A61K51/10 ,  B82Y5/00 ,  B82Y10/00 ,  B82Y30/00 ,  C07K16/30

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.

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，可检测标记或标签， 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：US08883160B2

公开(公告)日：2014-11-11

申请号：US13036820

申请日：2011-02-28

Applicant: Chien-Hsing Chang ,  David M. Goldenberg

Inventor： Chien-Hsing Chang ,  David M. Goldenberg

IPC: C07K16/28 ,  A61K47/48 ,  A61K51/08 ,  A61K51/10 ,  C12N9/12 ,  C07K14/47

CPC classification number: C07K16/46 ,  A61K47/6811 ,  A61K47/6849 ,  A61K47/6851 ,  A61K51/08 ,  A61K51/1027 ,  A61K51/1045 ,  C07K14/47 ,  C07K2317/31 ,  C07K2317/55 ,  C07K2317/732 ,  C07K2317/734 ,  C07K2319/70 ,  C12N9/12

Abstract: The prediction of protein function as well as the reconstruction of evolutionary genesis employing sequence comparison at large is still the most powerful tool in sequence analysis. Due to the exponential growth of the number of known protein sequences and the subsequent quadratic growth of the similarity matrix, the computation of the Similarity Matrix of Proteins (SIMAP) becomes a computational intensive task. The SIMAP database provides a comprehensive and up-to-date pre-calculation of the protein sequence similarity matrix, sequence-based features and sequence clusters. As of September 2009, SIMAP covers 48 million proteins and more than 23 million non-redundant sequences. Novel features of SIMAP include the expansion of the sequence space by including databases such as ENSEMBL as well as the integration of metagenomes based on their consistent processing and annotation. Furthermore, protein function predictions by Blast2GO are pre-calculated for all sequences in SIMAP and the data access and query functions have been improved. SIMAP assists biologists to query the up-to-date sequence space systematically and facilitates large-scale downstream projects in computational biology. Access to SIMAP is freely provided through the web portal for individuals (http://mips.gsf.de/simap/) and for programmatic access through DAS (http://webclu.bio.wzw.tum.de/das/) and Web-Service (http://mips.gsf.de/webservices/services/SimapService2.0?wsd1).

Abstract translation: 本文公开了包含选自AKAP蛋白质和选自蛋白激酶A调节亚基的DDD部分的AD部分的方法和组合物封闭和锁定（DNL）复合物。 还公开了包含连接到效应子部分的AD部分或DDD部分的融合蛋白。 DDD部分形成结合AD部分形成DNL复合物的二聚体。 效应部分可以选自产生一种或多种生理效应的广泛范围的已知效应部分，包括但不限于细胞死亡。 DNL复合物可进一步包含一种或多种诊断和/或治疗剂。 DNL复合物可用于治疗和/或诊断各种疾病或病症。

公开(公告)号：US08722047B2

公开(公告)日：2014-05-13

申请号：US12754140

申请日：2010-04-05

Applicant: David M. Goldenberg ,  Hans J. Hansen ,  Chien-Hsing Chang

Inventor： David M. Goldenberg ,  Hans J. Hansen ,  Chien-Hsing Chang

IPC: C07K16/28 ,  C07K16/46 ,  A61K39/395 ,  C07H21/04

CPC classification number: C07K16/2833 ,  A61K39/3955 ,  A61K39/39558 ,  A61K45/06 ,  A61K47/6849 ,  A61K47/6867 ,  A61K51/1027 ,  A61K51/1093 ,  A61K2039/505 ,  A61K2039/507 ,  C07K16/28 ,  C07K16/2887 ,  C07K16/4241 ,  C07K19/00 ,  C07K2317/24 ,  C07K2317/52 ,  C07K2317/56 ,  C07K2317/565 ,  C07K2317/71 ,  C07K2317/73 ,  C07K2317/732 ,  C07K2317/734 ,  C07K2317/75 ,  C07K2317/92

Abstract: The present invention concerns compositions and methods of use of humanized anti-HLA-DR antibodies. In preferred embodiments, the antibodies induce apoptosis and inhibit proliferation of lymphoma cells without inducing CDC or ADCC. In more preferred embodiments, the humanized anti-HLA-DR antibodies bind to the same epitope of HLA-DR as, or compete for binding to HLA-DR with, a murine L243 antibody. Most preferably, the humanized anti-HLA-DR antibody exhibits a higher affinity for HLA-DR than the parental murine antibody. The humanized HLA-DR antibody is of use for therapy of various diseases such as cancer, autoimmune disease or immune dysregulatory function, and is of particular use for therapy of B cell lymphomas and leukemias. In most preferred embodiments, the humanized anti-HLA-DR antibody is capable of inducing at least partial remission of lymphomas that are resistant to other B cell antibodies, such as rituximab.

Abstract translation: 本发明涉及使用人源化抗HLA-DR抗体的组合物和方法。 在优选的实施方案中，抗体诱导凋亡并抑制淋巴瘤细胞的增殖而不诱导CDC或ADCC。 在更优选的实施方案中，人源化抗HLA-DR抗体与鼠L243抗体结合HLA-DR相同的表位或与鼠L243抗体竞争结合HLA-DR。 最优选地，人源化抗HLA-DR抗体对亲本鼠抗体的HLA-DR表现出更高的亲和力。 人源化HLA-DR抗体可用于治疗各种疾病如癌症，自身免疫疾病或免疫调节功能，并且特别用于治疗B细胞淋巴瘤和白血病。 在最优选的实施方案中，人源化抗HLA-DR抗体能够诱导对其它B细胞抗体如利妥昔单抗有抗性的淋巴瘤的至少部分缓解。

公开(公告)号：US08597659B2

公开(公告)日：2013-12-03

申请号：US13219940

申请日：2011-08-29

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

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

IPC: A61K39/44 ,  A61K39/00 ,  A61K38/18 ,  A61K38/20 ,  A61K38/21 ,  A61K39/385 ,  C07K16/28 ,  C07K16/30 ,  C07K14/505 ,  C07K14/535 ,  C07K14/56 ,  A61K39/395 ,  C07K16/44

CPC classification number: A61K47/48423 ,  A61K39/395 ,  A61K47/65 ,  A61K47/6813 ,  A61K47/6853 ,  A61K51/1048 ,  A61K2039/505 ,  B82Y5/00 ,  B82Y10/00 ,  B82Y30/00 ,  C07K16/2803 ,  C07K16/283 ,  C07K16/2833 ,  C07K16/2863 ,  C07K16/2887 ,  C07K16/3007 ,  C07K16/44 ,  C07K16/468 ,  C07K2317/31 ,  C07K2317/55 ,  C07K2317/732 ,  C07K2317/734 ,  C07K2319/00 ,  C07K2319/30 ,  C07K2319/70

Abstract: The present invention concerns methods and compositions for forming cytokine-antibody complexes using dock-and-lock technology. In preferred embodiments, the cytokine-MAb DNL complex comprises an IgG antibody attached to two AD (anchor domain) moieties and four cytokines, each attached to a DDD (docking and dimerization domain) moiety. The DDD moieties form dimers that bind to the AD moieties, resulting in a 2:1 ratio of DDD to AD. The cytokine-MAb complex exhibits improved pharmacokinetics, with a significantly longer serum half-life than either naked cytokine or PEGylated cytokine. The cytokine-MAb complex also exhibits significantly improved in vitro and in vivo efficacy compared to cytokine alone, antibody alone, unconjugated cytokine plus antibody or cytokine-MAb DNL complexes incorporating an irrelevant antibody. In more preferred embodiment the cytokine is G-CSF, erythropoietin or INF-α2b.

Abstract translation: 本发明涉及使用基座和锁定技术形成细胞因子 - 抗体复合物的方法和组合物。 在优选的实施方案中，细胞因子-MAb DNL复合物包含连接到两个AD（锚结构域）部分的IgG抗体和四个细胞因子，每个连接到DDD（对接和二聚化结构域）部分。 DDD部分形成与AD部分结合的二聚体，导致DDD与AD的比例为2:1。 细胞因子-MAb复合物表现出改善的药代动力学，其具有比裸细胞因子或聚乙二醇化细胞因子显着更长的血清半衰期。 细胞因子-MAb复合物与单独的细胞因子，单独的抗体，未缀合的细胞因子+抗体或掺入无关抗体的细胞因子-MAb DNL复合物相比，还显示出显着改善的体外和体内功效。 在更优选的实施方案中，细胞因子是G-CSF，红细胞生成素或INF-α2b。

公开(公告)号：US08491896B2

公开(公告)日：2013-07-23

申请号：US12537803

申请日：2009-08-07

Applicant: David M. Goldenberg ,  Hans J. Hansen ,  Chien-Hsing Chang ,  David V. Gold

Inventor： David M. Goldenberg ,  Hans J. Hansen ,  Chien-Hsing Chang ,  David V. Gold

IPC: A61K39/395

CPC classification number: A61K51/088 ,  A61K47/6897 ,  A61K51/0406 ,  A61K51/0491 ,  A61K51/08 ,  A61K51/109 ,  A61K2039/505 ,  A61K2039/507 ,  B82Y5/00 ,  C07K16/303 ,  C07K16/3092 ,  C07K16/44 ,  C07K2317/24 ,  C07K2317/31 ,  C07K2317/34 ,  C07K2317/54 ,  C07K2317/55 ,  C07K2317/565

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 subject antibodies show a number of novel and useful therapeutic 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. In preferred embodiments, the antibodies bind to pancreatic cancer mucins. The antibodies and fragments are of use for the detection, diagnosis and/or treatment of cancer, such as pancreatic cancer. The antibodies, such as PAM4 antibodies, bind to a PAM4 antigen that shows unique cell and tissue distributions compared with other known antibodies such as CA19.9, DUPAN2, SPAN1, Nd2, B72.3, and Lea and Le(y) antibodies that bind to the Lewis antigens.

公开(公告)号：US08481041B2

公开(公告)日：2013-07-09

申请号：US13288202

申请日：2011-11-03

Applicant: Chien-Hsing Chang ,  David M. Goldenberg

Inventor： Chien-Hsing Chang ,  David M. Goldenberg

IPC: A61K39/00 ,  C07K16/08 ,  C07K19/00

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.

Abstract translation: 本发明涉及用于治疗受试者中HIV感染的方法和组合物，其利用与抗体，抗体片段或PEG连接的至少一种抗HIV治疗剂的DNL复合物。 在优选的实施方案中，抗体或片段与选自gp120，gp41，CD4和CCR5的抗原结合。 在更优选的实施方案中，抗体是P4 / D10或2G12，尽管其它抗HIV抗体是已知的并且可以被利用。 在最优选的实施方案中，抗HIV治疗剂是融合抑制剂，例如T20，T61，T651，T1249，T2635，CP32M或T-1444，尽管其它抗HIV治疗剂是已知的并且可以被利用。 DNL复合物可以单独施用，或者可以与一种或多种另外的抗HIV治疗剂共同施用。

公开(公告)号：US20130034492A1

公开(公告)日：2013-02-07

申请号：US13606899

申请日：2012-09-07

Applicant: Hans J. Hansen ,  Chien-Hsing Chang ,  David M. Goldenberg

Inventor： Hans J. Hansen ,  Chien-Hsing Chang ,  David M. Goldenberg

IPC: A61K39/395 ,  A61P29/00 ,  A61P5/00 ,  A61P31/00 ,  A61K51/00 ,  A61K51/10

CPC classification number: C07K16/3007 ,  A61K39/39558 ,  A61K47/55 ,  A61K47/60 ,  A61K47/6801 ,  A61K47/6807 ,  A61K47/6813 ,  A61K47/6815 ,  A61K47/6817 ,  A61K47/6819 ,  A61K47/6829 ,  A61K47/6849 ,  A61K47/6851 ,  A61K47/6853 ,  A61K49/0058 ,  A61K49/221 ,  A61K51/088 ,  A61K51/1027 ,  A61K51/1093 ,  A61K51/1096 ,  A61K2039/505 ,  A61K2039/545 ,  C07K14/54 ,  C07K16/2803 ,  C07K16/3076 ,  C07K2317/24 ,  C07K2317/31 ,  C07K2317/33 ,  C07K2317/515 ,  C07K2317/53 ,  C07K2317/55 ,  C07K2317/56 ,  C07K2317/565 ,  C07K2317/567 ,  C07K2317/76 ,  C07K2317/92 ,  C07K2319/00 ,  C07K2319/30 ,  A61K2300/00

Abstract: The present invention provides compositions and methods of use of humanized, chimeric or human Class I anti-CEA antibodies or fragments thereof, preferably comprising the light chain variable region CDR sequences SASSRVSYIH (SEQ ID NO:1); GTSTLAS (SEQ ID NO:2); and QQWSYNPPT (SEQ ID NO:3); and the heavy chain variable region CDR sequences DYYMS (SEQ ID NO:4); FIANKANGHTTDYSPSVKG (SEQ ID NO:5); and DMGIRWNFDV (SEQ ID NO:6). The Class I anti-CEA antibodies or fragments are useful for treating diseases, such as cancer, wherein the diseased cells express CEACAM5 and/or CEACAM6 antigens. The Class I anti-CEA antibodies or fragments are also of use for interfering with specific processes, such as metastasis, invasiveness and/or adhesion of cancer cells, or for enhancing sensitivity of cancer cells to cytotoxic agents and have favorable effects on the survival of subjects with cancer.

公开(公告)号：US08338140B2

公开(公告)日：2012-12-25

申请号：US13246389

申请日：2011-09-27

Applicant: Serengulam V. Govindan ,  Sung-Ju Moon ,  David M. Goldenberg ,  Chien-Hsing Chang

Inventor： Serengulam V. Govindan ,  Sung-Ju Moon ,  David M. Goldenberg ,  Chien-Hsing Chang

IPC: C07D491/22 ,  C07G11/00 ,  C07K16/00 ,  C07K9/00 ,  C08B37/02 ,  C08B37/16

CPC classification number: A61K47/48315 ,  A61K31/4745 ,  A61K31/704 ,  A61K38/05 ,  A61K47/556 ,  A61K47/61 ,  A61K47/62 ,  A61K47/645 ,  A61K47/646 ,  A61K47/65 ,  A61K47/665 ,  A61K47/6951 ,  B82Y5/00 ,  C07K14/001 ,  C08B37/0021 ,  C08G83/003 ,  C08G83/004 ,  Y02A50/403

Abstract: The present invention concerns methods and compositions for delivery of therapeutic agents to target cells, tissues or organisms. In preferred embodiments, the therapeutic agents are delivered in the form of therapeutic-loaded polymers that may comprise many copies of one or more therapeutic agents. In more preferred embodiments, the polymer may be conjugated to a peptide moiety that contains one or more haptens, such as HSG. The agent-polymer-peptide complex may be delivered to target cells by, for example, a pre-targeting technique utilizing bispecific or multispecific antibodies or fragments, having at least one binding arm that recognizes the hapten and at least a second binding arm that binds specifically to a disease or pathogen associated antigen, such as a tumor associated antigen. Methods for synthesizing and using such therapeutic-loaded polymers and their conjugates are provided.

Abstract translation: 本发明涉及用于将治疗剂递送至靶细胞，组织或生物体的方法和组合物。 在优选的实施方案中，治疗剂以治疗负荷聚合物的形式递送，其可以包含许多拷贝的一种或多种治疗剂。 在更优选的实施方案中，聚合物可以与含有一种或多种半抗原如HSG的肽部分缀合。 药剂 - 聚合物 - 肽复合物可以通过例如利用双特异性或多特异性抗体或片段的预靶向技术递送至靶细胞，所述双特异性或多特异性抗体或片段具有识别半抗原的至少一个结合臂和至少一个结合的结合臂 具体涉及疾病或病原体相关抗原，例如肿瘤相关抗原。 提供了合成和使用这种治疗负载型聚合物及其共轭物的方法。

公开(公告)号：US08333971B2

公开(公告)日：2012-12-18

申请号：US11745692

申请日：2007-05-08

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

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

IPC: A61K39/00 ,  A61K39/395

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抗体或片段可以与多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 。