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1. 发明申请

WO2017096368A1 BI-SPECIFIC MONOVALENT DIABODIES THAT ARE CAPABLE OF BINDING CD19 AND CD3, AND USES THEREOF 审中-公开
标题翻译：具有结合CD19和CD3能力的双特异性双价糖尿病及其用途
公开(公告)号：WO2017096368A1
公开(公告)日：2017-06-08
申请号：PCT/US2016/064958
申请日：2016-12-05
申请人： MACROGENICS, INC.
发明人： BONVINI, Ezio , JOHNSON, Leslie, S. , KOENIG, Scott , LAM, Chia-Ying, Kao , LIU, Liqin , MOORE, Paul, A.
IPC分类号： A61K39/00 , A61K39/395 , C07K16/00 , C07K16/18 , C07K16/28
CPC分类号： A61K39/39558 , A61K31/497 , A61K31/505 , A61K31/519 , A61K39/39541 , A61K47/6803 , A61K47/6849 , A61K47/6879 , A61K2039/505 , A61P35/00 , C07K16/2803 , C07K16/2809 , C07K16/3061 , C07K2317/31 , C07K2317/33 , C07K2317/35 , C07K2317/52 , C07K2317/524 , C07K2317/526 , C07K2317/56 , C07K2317/626 , C07K2317/64 , C07K2317/92 , C07K2317/94 , A61K2300/00
摘要： The present invention is directed to a combination therapy involving the administration of: (1) a bi-specific molecule capable of specifically binding to CD19 and to CD3 ( i.e. , a CD19 x CD3 bi-specific molecule), and (2) a Bruton's Tyrosine Kinase (BTK) inhibitor for the treatment of disease, in particular treatment of a disease associated with or characterized by the expression of CD 19. Preferably, such a CD 19 x CD3 bi-specific molecules are bi-specific monovalent diabodies. The invention is directed to pharmaceutical compositions that contain such a CD19 x CD3 bi-specific molecule, a BTK inhibitor, or a combination of such agents. The invention is additionally directed to methods for the use of such pharmaceutical compositions in the treatment of disease, in particular, treatment of a cancer associated with or characterized by the expression of CD 19.
摘要翻译：本发明涉及一种联合疗法，其涉及施用以下物质：（1）能够特异性结合CD19和CD3（即α CD19×CD3双特异性分子）和（2）布鲁顿氏酪氨酸激酶（BTK）抑制剂，用于治疗疾病，特别是治疗与CD19表达相关或以CD19表达为特征的疾病。优选地，这种CD19 x CD3双特异性分子是双特异性单价双抗体。本发明涉及含有这种CD19xCD3双特异性分子，BTK抑制剂或这些试剂的组合的药物组合物。本发明另外涉及使用此类药物组合物治疗疾病，特别是治疗与CD 19表达相关或以其为特征的癌症的方法。

2. 发明申请

WO2016122702A1 MULTIVALENT MOLECULES COMPRISING DR5-BINDING DOMAINS 审中-公开
标题翻译：包含DR5结合域的多重分子
公开(公告)号：WO2016122702A1
公开(公告)日：2016-08-04
申请号：PCT/US2015/033099
申请日：2015-05-29
申请人： MACROGENICS, INC.
发明人： MOORE, Paul, A. , JOHNSON, Leslie, S. , LI, Jonathan, C. , SHAH, Kalpana
IPC分类号： C07K16/28
CPC分类号： C07K16/2878 , A61K2039/505 , C07K16/30 , C07K2317/24 , C07K2317/35 , C07K2317/622 , C07K2317/73 , C07K2317/92
摘要： The present invention is directed to multivalent DR5 -Binding Molecules that comprise Binding Domain(s) of anti-DR5 antibodies, and particularly Binding Domain(s) of anti-human DR5 antibodies. The DR5 -Binding Molecules of the present invention include bivalent and tetravalent molecules having two, three or four DR5-Binding Domains each capable of binding human DR5. In particular, the present invention is directed to multivalent DR5 -Binding Molecules that comprise diabodies, and more particularly, diabodies that comprise a covalently bonded complex of two or more polypeptide chains. The invention particularly pertains to such multivalent DR5 -Binding Molecules that comprise fragments of the anti-DR5 antibodies DR5 mAb 1 and/or DR5 mAb 2, and/or humanized and chimeric versions of such antibodies.
摘要翻译：本发明涉及包含抗DR5抗体的结合域，特别是抗人DR5抗体的结合结构域的多价DR5-结合分子。本发明的DR5-结合分子包括具有两个，三个或四个能结合人DR5的DR5结合结构域的二价和四价分子。特别地，本发明涉及包含双抗体的多价DR5-结合分子，更具体地，涉及包含两个或多个多肽链的共价键合复合物的双抗体。本发明特别涉及包含抗DR5抗体DR5mAb1和/或DR5mAb2的片段，和/或这种抗体的人源化和嵌合形式的多价DR5-结合分子。

3. 发明申请

WO2016048938A1 BI-SPECIFIC MONOVALENT DIABODIES THAT ARE CAPABLE OF BINDING CD19 AND CD3, AND USES THEREOF 审中-公开
标题翻译：具有结合CD19和CD3的双特异性单价糖尿病及其用途
公开(公告)号：WO2016048938A1
公开(公告)日：2016-03-31
申请号：PCT/US2015/051314
申请日：2015-09-22
申请人： MACROGENICS, INC.
发明人： JOHNSON, Leslie, S. , BONVINI, Ezio , LAM, Chia-ying, Kao , MOORE, Paul, A. , LIU, Liqin , KOENIG, Scott
IPC分类号： C07K16/28
CPC分类号： C07K16/2803 , A61K39/39558 , A61K2039/505 , C07K16/2809 , C07K16/2896 , C07K16/3061 , C07K16/468 , C07K2317/31 , C07K2317/33 , C07K2317/35 , C07K2317/524 , C07K2317/526 , C07K2317/56 , C07K2317/569 , C07K2317/626 , C07K2317/73 , C07K2317/90 , C07K2317/92 , C07K2317/94
摘要： CD 19 x CD3 bi-specific monovalent diabodies, and particularly, CD 19 x CD3 bi- specific monovalent Fc diabodies, are capable of simultaneous binding to CD 19 and CD3, and are used in the treatment of hematologic malignancies.
摘要翻译： CD 19 x CD3双特异性单价双抗体，特别是CD 19 x CD3双特异性单价Fc双抗体能够同时结合CD19和CD3，并用于血液恶性肿瘤的治疗。

4. 发明申请

WO2010080538A1 COVALENT DIABODIES AND USES THEREOF 审中-公开
标题翻译：同性双胞胎及其用途
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。

5. 发明申请

WO2005110474A2 HUMANIZED FcγRIIB SPECIFIC ANTIBODIES AND METHODS OF USE THEREOF 审中-公开
标题翻译：人类FcγRIIB特异性抗体及其使用方法
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。

6. 发明申请

WO2019222104A1 OPTIMIZED GP41-BINDING MOLECULES AND USES THEREOF 审中-公开
公开(公告)号：WO2019222104A1
公开(公告)日：2019-11-21
申请号：PCT/US2019/032030
申请日：2019-05-13
申请人： MACROGENICS, INC. , DUKE UNIVERSITY
发明人： LAM, Chia-Ying, Kao , DIEDRICH, Gundo , NORDSTROM, Jeffrey, Lee , LIU, Liqin , JOHNSON, Leslie, S. , KOENIG, Scott , HAYNES, Barton, F. , FERRARI, Guido
IPC分类号： C07K16/10 , C07K16/28
摘要： The present invention is directed to optimized HIV-1 gp41-Binding Molecules having reduced immunogenicity. More specifically, the invention relates to optimized gp41-Binding Molecules that comprise a gp41-binding Variable Light Chain (VL) Domain and/or a gp41-binding Variable Heavy Chain (VH) Domain that has/have been optimized to reduce the immunogenicity of such Domain(s) upon administration to a recipient subject. The invention particularly pertains to gp41-Binding Molecules that are multispecific gp41-Binding Molecules (including bispecific diabodies (including DART® diabodies), BiTE®s, bispecific antibodies, trivalent binding molecules (including TRIDENT™ molecules), etc.) that comprise: (i) such optimized gp41-binding Variable Domain(s) and (ii) a domain capable of binding to an epitope of a molecule present on the surface of an effector cell. The invention is also directed to pharmaceutical compositions that comprise any of such gp41-Binding Molecules, and to methods involving the use of any of such gp41-Binding Molecules in the treatment of HIV-1 infection.

7. 发明申请

WO2017180813A1 NOVEL B7-H3 BINDING MOLECULES, ANTIBODY DRUG CONJUGATES THEREOF AND METHODS OF USE THEREOF 审中-公开
标题翻译：新的B7-H3结合分子，抗体药物偶联物及其使用方法
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。

8. 发明申请

WO2015200119A1 COVALENTLY BONDED DIABODIES HAVING IMMUNOREACTIVITY WITH PD-1 AND LAG-3, AND METHODS OF USE THEREOF 审中-公开
标题翻译：具有PD-1和LAG-3的具有免疫反应性的双重结合的双歧杆菌及其使用方法
公开(公告)号：WO2015200119A1
公开(公告)日：2015-12-30
申请号：PCT/US2015/036634
申请日：2015-06-19
申请人： MACROGENICS, INC.
发明人： BONVINI, Ezio , JOHNSON, Leslie, S. , SHAH, Kalpana , LA MOTTE-MOHS, Ross , MOORE, Paul, A. , KOENIG, Scott
IPC分类号： C07K16/28
CPC分类号： C07K16/2803 , C07K16/2818 , C07K16/468 , C07K2317/31 , C07K2317/626 , C07K2317/74
摘要： The present invention is directed to bi-specific diabodies that comprise two or more polypeptide chains and which possess at least one Epitope-Binding Site that is immunospecific for an epitope of PD-1 and at least one Epitope-Binding Site that is immunospecific for an epitope of LAG-3 (i.e., a "PD-I x LAG-3 bi-specific diabody"). More preferably, the present invention is directed to bi-specific diabodies that comprise four polypeptide chains and which possess two Epitope-Binding Sites that are immunospecific for one (or two) epitope(s) of PD-1 and two Epitope-Binding Site that are immunospecific for one (or two) epitope(s) of LAG-3 (i.e., a "PD-1 x LAG-3 bi-specific, tetra-valent diabody").
摘要翻译：本发明涉及包含两个或多个多肽链并且具有至少一个针对PD-1的表位具有免疫特异性的表位结合位点和至少一个对于一个或多个具有免疫特异性的表位结合位点的表位的双抗体 LAG-3表位（即，“PD-1×LAG-3双特异性双抗体”）。更优选地，本发明涉及包含四个多肽链并且具有对PD-1的一个或两个表位和两个表位结合位点具有免疫特异性的两个表位结合位点的双特异性双抗体，对于一个（或两个）LAG-3表位（即，“PD-1×LAG-3双特异性四价双抗体”）是免疫特异性的。

9. 发明申请

WO2012162067A3 CD3-BINDING MOLECULES CAPABLE OF BINDING TO HUMAN AND NON-HUMAN CD3 审中-公开
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.

10. 发明申请

WO2009123894A3 HER2/NEU-SPECIFIC ANTIBODIES AND METHODS OF USING SAME 审中-公开
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.

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