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公开(公告)号：US20230287117A1
公开(公告)日：2023-09-14
申请号：US17961442
申请日：2022-10-06
发明人： Samuel Davis , Eric Smith , Tong Zhang , Supriya Patel
IPC分类号： C07K16/28
CPC分类号： C07K16/2809 , C07K16/2803 , C07K16/2887 , C07K2317/24 , C07K2317/31 , C07K2317/526 , C07K2317/53 , C07K2317/71 , C07K2317/732 , C07K2317/90
摘要： The invention provides antibody heavy chain constant regions with a hinge region modified to reduce binding to Fcy receptors. The modification occurs within positions 233-236 by replacement of natural residues by glycine(s) and/or deletion(s). Such modifications can reduce binding of an antibody bearing such a constant region to Fcy receptors to background levels. The constant regions can be incorporated into any format of antibody or Fc fusion protein. Such antibodies or fusion proteins can be used in methods of treatment, particularly those in which the mechanisms of action of the antibody or Fc fusion protein is not primarily or at all dependent on effector functions, as is the case when an antibody inhibits a receptor-ligand interaction or agonizes a receptor.
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公开(公告)号：US20230272078A1
公开(公告)日：2023-08-31
申请号：US18077137
申请日：2022-12-07
发明人： Andrew J. Murphy , Dimitris Skokos , Janelle Waite , Erica Ullman , Aynur Hermann , Eric Smith , Lauric Haber , George D. Yancopoulos
CPC分类号： C07K16/2818 , C07K16/3069 , A61K2039/505
摘要： The present invention provides bispecific antigen-binding molecules comprising a first antigen-binding domain that specifically binds human CD28, and a second antigen-binding molecule that specifically binds human PSMA. In certain embodiments, the bispecific antigen-binding molecules of the present invention are capable of inhibiting the growth of tumors expressing PSMA, such as prostate tumors. The antibodies and bispecific antigen-binding molecules of the invention are useful for the treatment of diseases and disorders in which an up-regulated or induced targeted immune response is desired and/or therapeutically beneficial.
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公开(公告)号：US20230220101A1
公开(公告)日：2023-07-13
申请号：US17875295
申请日：2022-07-27
IPC分类号： C07K16/28
CPC分类号： C07K16/2809 , C07K16/2887 , C07K2317/31 , C07K2317/24 , C07K2317/565 , C07K2317/52
摘要： The present invention provides bispecific antibodies that bind to CD3 and tumor antigens and methods of using the same. According to certain embodiments, the bispecific antibodies of the invention exhibit reduced effector functions and have a unique binding profile with regard to Fcγ receptors. The bispecific antibodies are engineered to efficiently induce T cell-mediated killing of tumor cells. According to certain embodiments, the present invention provides bispecific antigen-binding molecules comprising a first antigen-binding domain that specifically binds human CD3, a second antigen-binding molecule that specifically binds human CD20, and an Fc domain that binds Fcγ receptors with a specific binding pattern. In certain embodiments, the bispecific antigen-binding molecules of the present invention are capable of inhibiting the growth of B-cell or melanoma tumors expressing CD20. The bispecific antibodies of the invention are useful for the treatment of various cancers as well as other CD20-related diseases and disorders.
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公开(公告)号：US20230094591A1
公开(公告)日：2023-03-30
申请号：US17749728
申请日：2022-05-20
发明人： Sean Stevens , Tammy T. Huang , Joel H. Martin , Jeanette L. Fairhurst , Ashique Rafique , Eric Smith , Kevin J. Pobursky , Nicholas J. Papadopoulos , James P. Fandl , Gang Chen , Margaret Karow
摘要： A human antibody or an antigen-binding fragment which binds human IL-6 receptor (hIL-6R) with a KD of about 500 pM or less and blocks IL-6 activity with an IC50 of 200 pM or less, is provided. In preferred embodiments, the antibody the antibody or antigen-binding fragment binds hIL-6R with an affinity at least 2-fold higher relative to its binding monkey IL-6R.
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公开(公告)号：US11548947B2
公开(公告)日：2023-01-10
申请号：US16448462
申请日：2019-06-21
发明人： Andrew J. Murphy , Dimitris Skokos , Janelle Waite , Erica Ullman , Aynur Hermann , Eric Smith , Lauric Haber , George D. Yancopoulos
摘要： The present invention provides bispecific antigen-binding molecules comprising a first antigen-binding domain that specifically binds human CD28, and a second antigen-binding molecule that specifically binds human PSMA. In certain embodiments, the bispecific antigen-binding molecules of the present invention are capable of inhibiting the growth of tumors expressing PSMA, such as prostate tumors. The antibodies and bispecific antigen-binding molecules of the invention are useful for the treatment of diseases and disorders in which an up-regulated or induced targeted immune response is desired and/or therapeutically beneficial.
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6.发明授权公开(公告)号：US11155621B2
公开(公告)日：2021-10-26
申请号：US15934447
申请日：2018-03-23
摘要： The present invention provides antibodies that bind to CD3 and methods of using the same. According to certain embodiments, the antibodies of the invention bind human CD3 with high affinity and induce human T cell proliferation. The invention includes antibodies that bind CD3 and induce T cell-mediated killing of tumor cells. According to certain embodiments, the present invention provides bispecific antigen-binding molecules comprising a first antigen-binding domain that specifically binds human CD3, and a second antigen-binding molecule that specifically binds human CD20. In certain embodiments, the bispecific antigen-binding molecules of the present invention are capable of inhibiting the growth of B-cell tumors expressing CD20. The antibodies and bispecific antigen-binding molecules of the invention are useful for the treatment of diseases and disorders in which an upregulated or induced targeted immune response is desired and/or therapeutically beneficial. For example, the antibodies of the invention are useful for the treatment of various cancers as well as other CD20-related diseases and disorders.
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公开(公告)号：US10738130B2
公开(公告)日：2020-08-11
申请号：US15713574
申请日：2017-09-22
发明人： Lauric Haber , Eric Smith , Marcus Kelly , Jessica R. Kirshner , Sandra Coetzee , Alison Crawford , Thomas Nittoli , Yashu Liu
IPC分类号： C07K16/30 , C07K16/46 , A61K39/395 , C07K16/28 , C07K16/44 , A61K47/68 , G01N33/574 , A61K39/00
摘要： Mucin 16 (MUC16) is highly expressed in ovarian cancer and expression on cancer cells is shown to protect tumor cells from the immune system. The present invention provides novel full-length human IgG antibodies that bind to human and MUC16 (monospecific antibodies). The present invention also provides novel bispecific antibodies (bsAbs) that bind to both MUC16 and CD3 and activate T cells via the CD3 complex in the presence of MUC16-expressing tumors. According to certain embodiments, the present invention provides bispecific antigen-binding molecules comprising a first antigen-binding domain that specifically binds human and monkey CD3, and a second antigen-binding molecule that specifically binds human and monkey MUC16. In certain embodiments, the bispecific antigen-binding molecules of the present invention are capable of inhibiting the growth of tumors expressing MUC16. The bispecific antigen-binding molecules of the invention are useful for the treatment of diseases and disorders in which an upregulated or induced MUC16-targeted immune response is desired and/or therapeutically beneficial. For example, the bispecific antibodies of the invention are useful for the treatment of various cancers, including ovarian cancer. The present invention also includes anti-MUC16 antibody drug conjugates which inhibit tumor growth in vivo. In some embodiments, the anti-MUC16 antibodies are useful in diagnostic methods for identifying the presence of MUC16 in tissue and/or plasma samples.
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公开(公告)号：US10550193B2
公开(公告)日：2020-02-04
申请号：US14661334
申请日：2015-03-18
摘要： The present invention provides bispecific antibodies that bind to CD3 and tumor antigens and methods of using the same. According to certain embodiments, the bispecific antibodies of the invention exhibit reduced effector functions and have a unique binding profile with regard to Fcγ receptors. The bispecific antibodies are engineered to efficiently induce T cell-mediated killing of tumor cells. According to certain embodiments, the present invention provides bispecific antigen-binding molecules comprising a first antigen-binding domain that specifically binds human CD3, a second antigen-binding molecule that specifically binds human CD20, and an Fc domain that binds Fcγ receptors with a specific binding pattern. In certain embodiments, the bispecific antigen-binding molecules of the present invention are capable of inhibiting the growth of B-cell or melanoma tumors expressing CD20. The bispecific antibodies of the invention are useful for the treatment of various cancers as well as other CD20-related diseases and disorders.
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公开(公告)号：US20190256606A1
公开(公告)日：2019-08-22
申请号：US16119695
申请日：2018-08-31
发明人： Sean Stevens , Tammy T. Huang , Joel H. Martin , Jeanette L. Fairhurst , Ashique Rafique , Eric Smith , Kevin J. Pobursky , Nicholas J. Papadopoulos , James P. Fandl , Gang Chen , Margaret Karow
IPC分类号： C07K16/28
摘要： A human antibody or an antigen-binding fragment which binds human IL-6 receptor (hIL-6R) with a KD of about 500 pM or less and blocks IL-6 activity with an IC50 of 200 pM or less, is provided. In preferred embodiments, the antibody the antibody or antigen-binding fragment binds hIL-6R with an affinity at least 2-fold higher relative to its binding monkey IL-6R.
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公开(公告)号：US20190031713A1
公开(公告)日：2019-01-31
申请号：US15961669
申请日：2018-04-24
发明人： Samuel Davis , Eric Smith , Douglas MacDonald , Kara Louise Olson
摘要： A bispecific antibody format providing ease of isolation is provided, comprising immunoglobulin heavy chain variable domains that are differentially modified in the CH3 domain, wherein the differential modifications are non-immunogenic or substantially non-immunogenic with respect to the CH3 modifications, and at least one of the modifications results in a differential affinity for the bispecific antibody for an affinity reagent such as Protein A, and the bispecific antibody is isolable from a disrupted cell, from medium, or from a mixture of antibodies based on its affinity for Protein A.
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