公开(公告)号：WO2010080538A1

公开(公告)日：2010-07-15

申请号：PCT/US2009/068577

申请日：2009-12-17

申请人： MACROGENICS, INC. ,  JOHNSON, Leslie, S. ,  HUANG, Ling

发明人： JOHNSON, Leslie, S. ,  HUANG, Ling

IPC分类号： A61K39/00

CPC分类号： C07K16/283 ,  A61K2039/505 ,  C07K16/2803 ,  C07K16/2809 ,  C07K16/32 ,  C07K16/44 ,  C07K2317/34 ,  C07K2317/52 ,  C07K2317/56 ,  C07K2317/626 ,  C07K2317/64 ,  C07K2317/73 ,  C07K2317/92 ,  C07K2319/00

摘要： The present invention is directed to diabody molecules and uses thereof in the treatment of a variety of diseases and disorders, including immunological disorders, infectious disease, intoxication and cancers. The diabody molecules of the invention comprise two polypeptide chains that associate to form at least two epitope binding sites, which may recognize the same or different epitopes on the same or differing antigens. Additionally, the antigens may be from the same or different molecules. The individual polypeptide chains of the diabody molecule may be covalently bound through non-peptide bond covalent bonds, such as, but not limited to, disulfide bonding of cysteine residues located within each polypeptide chain. In particular embodiments, the diabody molecules of the present invention further comprise an Fc region, which allows antibody- like functionality to engineered into the molecule.

摘要翻译： 本发明涉及双抗体分子及其在治疗各种疾病和病症（包括免疫学疾病，感染性疾病，中毒和癌症）中的用途。 本发明的双抗体分子包含两个缔合以形成至少两个表位结合位点的多肽链，其可识别相同或不同抗原上相同或不同的表位。 另外，抗原可以来自相同或不同的分子。 双抗体分子的单个多肽链可以通过非肽键共价键共价结合，例如但不限于位于每个多肽链内的半胱氨酸残基的二硫键。 在具体实施方案中，本发明的双抗体分子还包含Fc区，其允许类似抗体的功能改造成分子。

公开(公告)号：WO2008105886A2

公开(公告)日：2008-09-04

申请号：PCT/US2007/069767

申请日：2007-05-25

申请人： MACROGENICS, INC. ,  JOHNSON, Leslie S. ,  HUANG, Ling

发明人： JOHNSON, Leslie S. ,  HUANG, Ling

IPC分类号： A61K39/395 ,  A61P43/00 ,  C07H21/04 ,  C07K16/18 ,  C12N15/00 ,  C12N5/06 ,  C12P21/04 ,  G01N33/564

CPC分类号： A61K39/39 ,  A61K2039/505 ,  A61K2039/55516 ,  C07K16/283 ,  C07K2317/24 ,  C07K2317/34 ,  C07K2317/52 ,  G01N33/564 ,  G01N33/6893 ,  G01N2800/24

摘要： The present invention relates to humanized FcγRIIB antibodies, fragments, and variants thereof that bind human FcγRIIB with a greater affinity than said antibody binds FcγRIIA. The invention encompasses the use of the humanized antibodies of the invention for the treatment of any disease related to loss of balance of Fc receptor mediated signaling, such as cancer, autoimmune and inflammatory disease. The invention provides methods of enhancing the therapeutic effect of therapeutic antibodies by administering the humanized antibodies of the invention to enhance the effector function of the therapeutic antibodies. The invention also provides methods of enhancing the efficacy of a vaccine composition by administering the humanized antibodies of the invention. The invention encompasses methods for treating an autoimmune disease and methods for elimination of cancer cells that express FcγRIIB.

摘要翻译： 本发明涉及以比所述抗体更大的亲和力结合FcγRIIA的结合人FcγRIIB的人源化FcγRIIB抗体，其片段和变体。 本发明包括本发明的人源化抗体用于治疗与Fc受体介导的信号传导的平衡丧失有关的任何疾病（例如癌症，自身免疫性和炎症性疾病）的用途。 本发明提供了通过施用本发明的人源化抗体来增强治疗性抗体的治疗效果以增强治疗性抗体的效应子功能的方法。 本发明还提供了通过施用本发明的人源化抗体来增强疫苗组合物的功效的方法。 本发明包括治疗自身免疫疾病的方法和消除表达FcγRIIB的癌细胞的方法。

公开(公告)号：WO2006088494A9

公开(公告)日：2006-08-24

申请号：PCT/US2005/024645

申请日：2005-07-12

申请人： MACROGENICS, INC. ,  STAVENHAGEN, Jeffrey ,  VIJH, Sujata ,  RANKIN, Christopher ,  GORLATOV, Sergey ,  HUANG, Ling

发明人： STAVENHAGEN, Jeffrey ,  VIJH, Sujata ,  RANKIN, Christopher ,  GORLATOV, Sergey ,  HUANG, Ling

IPC分类号： A61K39/395 ,  C07K16/28

摘要： The present invention relates to molecules, particularly polypeptides, more particularly immunoglobins ( e.g ., antibodies), comprising a variant Fc region, wherein said variant Fc region comprises at least one amino acid modification relative to a wild-type Fc region, which variant Fc region binds FcγRIIIA and/or FcγRIIA with a greater affinity, relative to a comparable molecule comprising the wild-type Fc region. The molecules of the invention are particularly useful in preventing, treating, or ameliorating one or more symptoms associated with a disease, disorder, or infection. The molecules of the invention are particularly useful for the treatment or prevention of a disease or disorder where an enhanced efficacy of effector cell function ( e.g ., ADCC) mediated by FcγR is desired, e.g ., cancer, infectious disease, and in enhancing the therapeutic efficacy of therapeutic antibodies the effect of which is mediated by ADCC.

公开(公告)号：WO2005110474A2

公开(公告)日：2005-11-24

申请号：PCT/US2005/016260

申请日：2005-05-10

申请人： MACROGENICS, INC. ,  JOHNSON, Leslie, S. ,  HUANG, Ling

发明人： JOHNSON, Leslie, S. ,  HUANG, Ling

IPC分类号： A61K39/395

CPC分类号： C07K16/283 ,  A61K2039/505 ,  C07K2317/24 ,  C07K2317/34

摘要： The present invention relates to humanized FcγRIIB antibodies, fragments, and variants thereof that bind human FcγRIIB with a greater affinity than said antibody binds FcγRIIA. The invention encompasses the use of the humanized antibodies of the invention for the treatment of any disease related to loss of balance of Fc receptor mediated signaling, such as cancer, autoimmune and inflammatory disease. The invention provides methods of enhancing the therapeutic effect of therapeutic antibodies by administering the humanized antibodies of the invention to enhance the effector function of the therapeutic antibodies. The invention also provides methods of enhancing the efficacy of a vaccine composition by administering the humanized antibodies of the invention. The invention encompasses methods for treating an autoimmune disease and methods for elimination of cancer cells that express FcγRIIB.

摘要翻译： 本发明涉及以与抗体结合FcγRIIA更大的亲和力结合人FcγRIIB的人源化FcγRIIB抗体，其片段和变体。 本发明包括本发明的人源化抗体用于治疗与Fc受体介导的信号传导的平衡失去相关的任何疾病（例如癌症，自身免疫性和炎性疾病）的用途。 本发明提供了通过施用本发明的人源化抗体来增强治疗性抗体的治疗效果以增强治疗性抗体的效应子功能的方法。 本发明还提供了通过施用本发明的人源化抗体来增强疫苗组合物的功效的方法。 本发明包括治疗自身免疫疾病的方法和用于消除表达FcγRIIB的癌细胞的方法。

公开(公告)号：WO2017180813A1

公开(公告)日：2017-10-19

申请号：PCT/US2017/027317

申请日：2017-04-13

申请人： MACROGENICS, INC.

发明人： LOO, Deryk, T. ,  HUANG, Ling ,  JOHNSON, Leslie, S. ,  SON, Thomas ,  SCRIBNER, Juniper ,  BONVINI, Ezio

IPC分类号： A61K39/395 ,  A61K47/68 ,  C07K16/28

摘要： The present invention is directed to novel B7-H3-binding molecules capable of binding to human and non-human B7-H3, and in particular to such molecules that are cross-reactive with B7-H3 of a non-human primate (e.g., a cynomolgus monkey). The invention additionally pertains to B7-H3-binding molecules that comprise Variable Light Chain and/or Variable Heavy Chain (VH) Domains that have been humanized and/or deimmunized so as to exhibit a reduced immunogenicity upon administration to recipient subjects. The invention particularly pertains to bispecific, trispecific or multispecific B7-H3-binding molecules, including bispecific diabodies, BiTEs, bispecific antibodies, trivalent binding molecules, etc. that comprise: (i) such B7-H3-binding Variable Domains and (ii) a domain capable of binding to an epitope of a molecule present on the surface of an effector cell. The invention also particularly pertains to a molecule that comprises the human B7-H3 binding domain of a humanized anti-human B7-H3 antibody conjugated to at least one drug moiety (a "B7-H3-ADC").

摘要翻译： 本发明涉及能够结合人和非人B7-H3的新型B7-H3结合分子，特别是涉及与B7-H3交叉反应的分子 非人灵长类动物（例如食蟹猴）。 本发明另外涉及包含可变轻链和/或可变重链（VH）结构域的B7-H3结合分子，所述可变轻链和/或可变重链（VH）结构域已被人源化和/或去免疫化，以便在给予受体对象时表现出降低的免疫原性。 本发明特别涉及双特异性，三特异性或多特异性B7-H3结合分子，包括双特异性双抗体，BiTE，双特异性抗体，三价结合分子等，其包含：（i）此类结合B7-H3的可变结构域和（ii） 能够结合存在于效应细胞表面上的分子的表位的结构域。 本发明还特别涉及包含与至少一个药物部分（“B7-H3-ADC”）缀合的人源化抗人B7-H3抗体的人B7-H3结合结构域的分子。

公开(公告)号：WO2012162067A3

公开(公告)日：2012-11-29

申请号：PCT/US2012/038219

申请日：2012-05-16

申请人： MACROGENICS, INC. ,  HUANG, Ling ,  JOHNSON, Leslie, S.

发明人： HUANG, Ling ,  JOHNSON, Leslie, S.

IPC分类号： C07K16/00

摘要： CD3-binding molecules capable of binding to human and non-human CD3, and in particular to such molecules that are cross-reactive with CD3 of a non-human mammal (e.g., a cynomolgus monkey) are presented. Uses of such antibodies and antigen-binding fragments in the treatment of cancer, autoimmune and/or inflammatory diseases and other conditions are presented.

公开(公告)号：WO2009123894A3

公开(公告)日：2009-10-08

申请号：PCT/US2009/038201

申请日：2009-03-25

申请人： MACROGENICS, INC. ,  JOHNSON, Leslie, S. ,  HUANG, Ling ,  TUAILLON, Nadine ,  BONVINI, Ezio

发明人： JOHNSON, Leslie, S. ,  HUANG, Ling ,  TUAILLON, Nadine ,  BONVINI, Ezio

IPC分类号： A61K39/00 ,  C12P21/08

摘要： This invention relates to antibodies that specifically bind HER2/neu, and particularly chimeric 4D5 antibodies to HER2/neu, which have reduced glycosylation as compared to known 4D5 antibodies. The invention also relates to methods of using the 4D5 antibodies and compositions comprising them in the diagnosis, prognosis and therapy of diseases such as cancer, autoimmune diseases, inflammatory disorders, and infectious disease.

公开(公告)号：WO2006031825A2

公开(公告)日：2006-03-23

申请号：PCT/US2005/032587

申请日：2005-09-13

申请人： MACROGENICS, INC. ,  JOHNSON, Leslie, S. ,  HUANG, Ling

发明人： JOHNSON, Leslie, S. ,  HUANG, Ling

IPC分类号： A61K39/42 ,  C07K16/08

CPC分类号： C07K16/1081 ,  A61K2039/505 ,  C07K2317/24 ,  C07K2317/565 ,  C07K2317/567 ,  G01N33/56983 ,  G01N2333/18 ,  G01N2469/20 ,  Y02A50/386 ,  Y02A50/388 ,  Y02A50/394 ,  Y02A50/396 ,  Y02A50/53 ,  Y02A50/60

摘要： The present invention relates to compositions comprising humanized antibodies or fragments thereof that immunospecifically bind to one or more antigens of a flavivirus, particularly of West Nile Virus (WNV) and methods for preventing, treating or ameliorating symptoms associated with a flavivirus, particularly of West Nile Virus (WNV) infection utilizing said compositions. In particular, the present invention relates to methods for preventing, treating or ameliorating to a human subject an effective amount of one or more humanized antibodies or fragments thereof that immunospecifically bind to a WNV antigen. The present invention also relates to detectable or diagnostic compositions comprising humanized antibodies or fragments thereof that immunospecifically bind to a WNV antigen and methods for detecting or diagnosing WNV infection utilizing said compositions.

摘要翻译： 本发明涉及包含免疫特异性结合黄病毒特别是西尼罗河病毒（WNV）的一种或多种抗原的人源化抗体或其片段的组合物，以及预防，治疗或改善相关症状的方法 与利用所述组合物的黄病毒，特别是西尼罗病毒（WNV）感染。 特别地，本发明涉及预防，治疗或改善人类受试者有效量的一种或多种免疫特异性结合WNV抗原的人源化抗体或其片段的方法。 本发明还涉及包含免疫特异性结合WNV抗原的人源化抗体或其片段的可检测或诊断组合物，以及利用所述组合物检测或诊断WNV感染的方法。

公开(公告)号：WO2019160904A1

公开(公告)日：2019-08-22

申请号：PCT/US2019/017772

申请日：2019-02-13

申请人： MACROGENICS, INC.

发明人： BONVINI, Ezio ,  HUANG, Ling ,  LAM, Chia-Ying, Kao ,  CHICHILI, Gurunadh, Reddy ,  ALDERSON, Ralph, Froman ,  MOORE, Paul, A. ,  JOHNSON, Leslie, S.

IPC分类号： A61K39/395 ,  C07K16/28 ,  C07K16/30 ,  C07K16/32 ,  C07K16/44

摘要： The present invention is directed to DA x CD3 Binding Molecules comprising a vCD3- Binding Domain, which comprises a CDRHI Domain, a CDRH2 Domain, a CDRH3 Domain, a CDRL I Domain, a CDRL2 Domain, and a CDRL3 Domain, at least one of which differs in amino acid sequence from the amino acid sequence of the corresponding CDR of a rCD3- Binding Domain, wherein the DA x CD3 Binding Molecule comprising such vCD3-Binding Domain exhibits an altered affinity for CD3, relative to a DA x CD3 Binding Molecule comprising such rCD3-Binding Domain. The invention particularly concerns to such DA x CD3 Binding Molecules comprising a vCD3-Binding Domain which exhibit reduced affinity for CD3 and are capable of mediating redirected killing of target cells expressing a DA and exhibit lower levels of cytokine release relative to a DA x CD3 Binding Molecule comprising a rCD3-Binding Domain. The invention particularly concerns the use of DA x CD3 Binding Molecules comprising a vCD3 -Binding Domain in the treatment of cancer and pathogen-associated diseases. The present invention is also directed to pharmaceutical compositions that comprise such molecule(s).

公开(公告)号：WO2015026892A1

公开(公告)日：2015-02-26

申请号：PCT/US2014/051790

申请日：2014-08-20

申请人： MACROGENICS, INC.

发明人： BONVINI, Ezio ,  JOHNSON, Leslie, S. ,  HUANG, Ling ,  MOORE, Paul, A. ,  CHICHILI, Gurunadh, Reddy ,  ALDERSON, Ralph, Froman

IPC分类号： A61K39/395 ,  C07K16/28 ,  C07K17/14

CPC分类号： C07K16/2896 ,  A61K2039/505 ,  C07K16/2809 ,  C07K16/2866 ,  C07K2317/31 ,  C07K2317/33 ,  C07K2317/56 ,  C07K2317/626 ,  C07K2317/73 ,  C07K2317/92 ,  C07K2319/30 ,  C07K2319/31

摘要： The present invention is directed to sequence-optimized CD 123 x CD3 bi-specific monovalent diabodies that are capable of simultaneous binding to CD 123 and CD3, and to the uses of such diabodies in the treatment of hematologic malignancies.

摘要翻译： 本发明涉及能够同时结合CD123和CD3的序列优化的CD123×CD3双特异性一抗双抗体，以及这种双抗体在治疗血液恶性肿瘤中的用途。