• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
  • 引用文献
  • 法律状态
  • 优先权
    • 专利摘要:

    公开号:ES2593583T9
    申请号:ES10708865.0T
    申请日:2010-03-10
    公开日:2017-06-05
    发明作者:Susan L. Kalled；Yen-Ming Hsu
    申请人:Biogen MA Inc；
    IPC主号:
    专利说明:

    image 1
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    Figure 5 depicts staining by flow cytometry for plasma cells (PC) in the human CD45 + compartment of splenocyte isolated from HSC / NSG mice treated with anti-BCMA antibody (chC12A3.2 or chC13F12.1) or human IgG1 control . The mice received an i.p. of Ab anti-BCMA or control of
    5 HIgG1 twice a week for 2 weeks. ** p <0.0001; * p = 0.0066.
    Figure 6 depicts flow cytometry staining for plasma cells (PC) in the human CD45 + compartment of splenocyte isolated from HSC / NSG mice treated with anti-BCMA antibody (chCHD5.1 or chA7D12.2) or human IgG1 control . The mice received an i.p. of anti-BCMA or control antibody
    10 of HIgG1 twice a week for 2 weeks.
    Table 1. Brief description of the sequences
    SEQ ID NO Sequence description
    one A7D12.2 mature heavy chain variable domain protein sequence
    2 A7D12.2 mature light chain variable domain protein sequence
    3 C11D5.3 mature heavy chain variable domain protein sequence
    4 mature light chain variable domain protein sequence A C11D5.3
    5 C12A3.2 mature heavy chain variable domain protein sequence
    6 C12A3.2 mature light chain variable domain protein sequence
    7 C13F12.1 mature heavy chain variable domain protein sequence
    8 C13F12.1 mature light chain variable domain protein sequence
    9 BCMA protein sequence
    10 huBCMA-huFc (as defined by N-terminal sequence analysis)
    eleven C11D5.3 mature light chain variable domain protein sequence B
    12 C11D5.3 mature light chain variable domain protein sequence C
    13 chA7D12.2 chimeric mature heavy chain protein sequence
    14 chA7D12.2 chimeric mature light chain protein sequence
    fifteen chC11 mature chimeric heavy chain protein sequence D5.3
    16 chC11 mature light chain protein sequence A chC11 D5.3
    17 chC11 mature chimeric light chain protein C sequence D5.3
    18 chC12A3.2 chimeric mature heavy chain protein sequence
    19 chC12A3.2 chimeric mature light chain protein sequence
    twenty chC13F12.1 chimeric mature heavy chain protein sequence
    twenty-one chC13F12.1 chimeric mature light chain protein sequence
    22 Humanized mature light chain variable domain sequence huC11D5.3L1
    2. 3 Humanized mature light chain variable domain sequence huC11D5.3L2
    24 Humanized mature light chain variable domain sequence huC11D5.3L3
    25 Humanized mature heavy chain variable domain sequence huC11D5.3H0
    26 Humanized mature heavy chain variable domain sequence huC11D5.3H1
    27 Humanized mature heavy chain variable domain sequence huC11D5.3H2
    28 Humanized mature heavy chain variable domain sequence huC11D5.3H3
    29 Humanized mature heavy chain variable domain sequence huC11D5.3H4
    30 Humanized mature light chain variable domain sequence huC12A3.2L0
    31 Humanized mature light chain variable domain sequence huC12A3.2L1
    32 Humanized mature light chain variable domain sequence huC12A3.2L2
    33 Humanized mature light chain variable domain sequence huC12A3.2L3
    3. 4 Humanized mature heavy chain variable domain sequence huC12A3.2H0
    35 Humanized mature heavy chain variable domain sequence huC12A3.2H1
    36 Humanized mature heavy chain variable domain sequence huC12A3.2H2
    37 Humanized mature heavy chain variable domain sequence huC12A3.2H3
    38 Humanized mature heavy chain variable domain sequence huC12A3.2H4
    39 Humanized mature light chain variable domain sequence huC13F12.1L0
    40 Humanized mature light chain variable domain sequence huC13F12.1L1
    41 Humanized mature light chain variable domain sequence huC13F12.1L2
    42 Humanized mature light chain variable domain sequence huC13F12.1 L3
    43 Humanized mature heavy chain variable domain sequence huC13F12.1H0
    44 Humanized mature heavy chain variable domain sequence huC13F12.1H1
    4
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    B. Antibody variable domain sequence
    The antibodies of the invention may comprise the heavy chain variable domain sequences of SEQ ID NO: 3, SEQ ID NO: 5 or SEQ ID NO: 7. The heavy chain variable domain sequences may consist essentially essentially of the SEQ ID NO: 3, SEQ ID NO: 5 or SEQ ID NO: 7.
    The antibodies of the invention may comprise the light chain variable domain sequences of SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 11, or SEQ ID NO: 12. Light chain variable domain sequences can basically consist of SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 11,
    10 wave SEQIDNO: 12.
    In addition, a variable domain sequence is described herein comprising a sequence that is at least 80%, at least 85%, at least 90%, or at least 95% identical to the selected sequence of the SEQ ID NO: 1, SEQ ID NO: 3, SEQ ID NO: 5, and SEQ ID NO: 7. In addition, a variable domain sequence comprising a sequence that is at least 80 is described herein. %, at least 85%, at least 90%, or at least 95% identical to the selected sequence of SEQ ID NO: 2, SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 8 , SEQ ID NO: 11, and SEQ ID NO: 12. Antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least one are also described herein. 90%, or at least 95% identical to SEQ ID NO: 1 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95% identical to SEQ ID NO: 2. Antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95 are also described herein. % identical to SEQ ID NO: 3 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95% identical to SEQ ID NO : 25 4, SEQ ID NO: 11, or SEQ ID NO: 12. Antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, are also described herein. at least 90%, or at least 95% identical to SEQ ID NO: 5 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95% identical to SEQ ID NO:
    6. Antibodies comprising a variable domain sequence are also described herein.
    30 heavy chain that is at least 80%, at least 85%, at least 90%, or at least 95% identical to SEQ ID NO: 7 and a light chain variable domain sequence that is at at least 80%, at least 85%, at least 90%, or at least 95% identical to SEQ ID NO: 8.
    The invention also provides antibodies with particular complementarity determining regions (CDRs). Table 2 defines the amino acid coordinates of CDR1, CDR2 and CDR3 of SEQ ID NO: 1 to 8, 11 and 12.
    Table 2. CDR amino acid coordinates
    SEQ ID NO Description
    3 C11D5.3 VH31-3550-6699-106
    4 C11D5.3 VL A24-3854-6093-101
    C12A3.2 VH 31-3550-6699-106
    6 C12A3.2 VL24-3854-6093-101
    7 C13F12.1 VH31-3550-6699-106
    8 C13F12.1 VL24-3854-6093-101
    eleven C11D5.3 VL B24-3854-6093-101
    12 C11D5.3 VL C24-3854-6093-101
    40 The CDRs are designated using the definitions of Kabat (Johnson and Wu (2000), Nucleic Acids Res 28: 214-218). As used herein, the "corresponding CDR" refers to the CDR in the most similar position within the variable domain amino acid sequence.
    The variable heavy chain antibody domain of the invention may comprise CDR such that one,
    Two or three of the CDRs are identical to the corresponding CDRs of SEQ ID NO: 3; identical to the corresponding CDRs of SEQ ID NO: 5; or identical to the corresponding CDRs of SEQ ID NO: 7. The antibody light chain variable domain of the invention may comprise CDRs such that one, two or three of the CDRs are identical to the corresponding CDRs of SEQ ID. NO: 4; identical to the corresponding CDRs of SEQ ID NO: 6; identical to the corresponding CDRs of SEQ ID NO: 8; identical to the corresponding CDRs of
    7
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    microencapsulated Biodegradable and biocompatible polymers, such as ethylene vinyl acetate, polyanhydrides, polyglycolic acid, collagen, polyorthoesters and polylactic acid can be used. The methods for preparing such formulations will be apparent to those skilled in the art. The materials can also be obtained commercially from Alza Corporation and Nova Pharmaceuticals, Inc. Liposomal suspensions (including liposomes
    5 directed to cells infected with monoclonal antibodies to viral antigens) can also be used as pharmaceutically acceptable carriers. Additionally, the antibodies or antibody fragments of the invention can be used to direct the liposomal suspensions to B lymphocytes or subclasses thereof, to which the particular antibody binds. These can be prepared according to methods known to those skilled in the art, for example, as described in US Patent No. 4,522,811.
    10 Parenteral compositions can be formulated in a unit dosage form to facilitate administration and achieve dosage uniformity. Unit dosage forms, as used herein, refer to physically separate units suitable as unit dosages for the subject to be treated; each unit containing a predetermined amount of antibody calculated for
    15 produce the desired therapeutic effect together with the necessary pharmaceutical vehicle. The specification for the unit dosage forms of the invention is subject to and depends directly on the unique characteristics of the active compound and the particular therapeutic effect that is desired to be achieved.
    Pharmaceutical compositions comprising an antibody of the invention may be included in a container, package or dispenser, together with instructions for administration. Example 1. Generation and conjugation with biotin of human anti-BCMA monoclonal antibodies
    Anti-BCMA monoclonal antibodies (mAb) were generated by immunizing female RBF mice with protein
    25 BCMA-Fc / KLH i.p. in CFA, followed by additional immunizations at regular intervals with IFA, except that the last stimulus used RIBI instead of IFA, before the fusion of splenocytes with the myeloma cell line FL653 according to the method of Harlow and Lane (1998), Using Antibodies: A Laboratory Manual: Portable Protocol No. I, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY. In summary, splenocytes isolated from a mouse 3 days after the final stimulus were washed twice and mixed in a 7: 1 ratio with cells of
    30 FL653 logarithmic phase myeloma with two washes. The cell mixture was separated into four, sedimented and incubated in PEG at 37 ° C for 1 min, during which time the cells were gently resuspended, followed by the careful addition of 10 ml of ice-cold DMEM. The cells were mixed, sedimented and resuspended in AAT hybridoma growth selection medium. The cell supernatants were analyzed to determine the specific reactivity for BCMA by ELISA and flow cytometry. Clones
    35 with a positive result for BCMA and negative for Fe specificity in an ELISA format, positive for cells transfected with BCMA and negative for cells transfected with mock, were expanded and subcloned. Four clones specific to BCMA were selected for further evaluation: C11D5.3 (IgG1), C12A3.2 (IgG1), C13F12.1 (IgG1) and A7D12.2 (IgG2b). The anti-BCMA monoclonal antibodies were conjugated with biotin for use in ELISA and FACS experiments described below using a kit of
    40 according to the manufacturer's recommendations (Molecular Probes, Eugene, OR). Example 2. Cloning of variable regions of murine human anti-BCMA monoclonal antibodies
    Total murine hybridoma cell cellular RNA was prepared using a Qiagen RNeasy mini kit, following the
    45 protocol recommended by the manufacturer. Variable regions encoding cDNAs of light and heavy chains were cloned by RT-PCR from total cellular RNA, using random hexamers to prime the first chain cDNA. For PCR amplification of the murine immunoglobulin variable domains with intact signal sequences, a cocktail of redundant direct primers that hybridize with multiple signal sequences of the murine immunoglobulin gene family and a single reverse primer was used.
    50 specific for the 5 'end of the murine constant domain. PCR was performed using the Clontech Advantage 2 polymerase mixture, following the protocol recommended by the manufacturer. The PCR products were gel purified and subcloned into the pCR2.1TOPO vector of Invitrogen using their TOPO cloning kit, following the protocol recommended by the manufacturer. The inserts of multiple independent subclones were sequenced to establish a consensus sequence. The N ends of mature immunoglobulin were
    55 consistent with those determined by Edman degradation from the hybridoma. Assignment to specific subsets was based on the BLAST analysis, using consensus immunoglobulin variable domain sequences from the Kabat database (Johnson and Wu (2000), Nucleic Acids Res 28: 214-218). The CDRs were designated using the definitions of Kabat (Johnson and Wu (2000), Nucleic Acids Res 28: 214-218).
    12
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    Markers used to exclude specific cell populations were anti-mouse CD45 and anti-human CD3. The cells identified as PC were human CD45 +, human CD19 +, human CD3 +, human CD27 +, human IgD and human CD38bright. To identify BCMA + lymphocytes, the anti-human BCMA mAB conjugated with biotin C12A3.2 and A7D12.2 were used.
    5 In vivo cell depletion test
    HSC / NSG mice 5-6 months of age received chimeric anti-BCMA mAB i.p. Human IgG1 without known reactivity (Protos Immunoresearch) was used as a negative control. Blood was collected to prepare serum for
    10 the analysis of human Ig isoform levels. At the end of the study, the spleen was removed, a single cell suspension was prepared, the RBCs were lysed and the cells were washed 3 times with 5% PBS / FCS and the amount of cells was determined. The cells were evaluated by flow cytometry to determine the cells of the T lineage, the cells of the B lineage and the plasma cells.
    15 Evaluation of human Ig isotypes in serum
    Serum human IgM and IgG levels were determined using an ELISA format (Bethyl Laboratories Inc., Montgomery, TX) and a human immunoglobulin isotype determination kit (Millipore, Billerica, MA), respectively, according to the protocol manufacturer.
    20 Results
    Analysis of HSC / NSG mice of 5-6 months of age revealed that, among the various cell subsets evaluated, BCMA + lymphocytes were only found in the B lymphocyte lineage. Within the lymphocyte lineage
    25 B, only BCMA was found in splenic PCs (human CD19 +, human CD27 +, IgD- and CD38 bright) (Figure 4) and not in untreated B lymphocytes (human CD19 +, human CD27 + and IgD +), lymphocytes Unchanged memory B (human GD19 +, human CD27 + and human IgD +) or memory B lymphocytes with changes (human CD19 +, human CD27 + and human IgD) (data not shown).
    30 To assess the ability of human anti-BCMA chimeric mAbs to deplete human PCs, HSC / NSG mice received various amounts of human anti-BCMA chimeric clones chACHD5.3, chC12A3.2, chC13F12.1 and chA7D12.2 (Example 7) twice a week ip for 2 weeks, after which the presence of splenic PCs was determined. Splenic PCs from the control group treated with HIgG1 were analyzed for BCMA expression using clones A7D12.2 and C12A3.2 and confirmed to express the
    35 BCMA cell surface (data not shown). The PCs were identified using the flow cytometric parameters described above, and the amounts of total cells were determined from the flow cytometric point diagrams (calculated as a percentage of the amount of total human cells). The amounts of untreated human B lymphocytes, human memory B lymphocytes unchanged and human memory B lymphocytes with changes were also determined.
    40 Treatment with chC12A3.2 (N = 5) resulted in a statistically significant decrease, of 93% and 95%, in the amount of splenic PC at the dose levels of 200 µg and 20 µg, respectively, compared with mice treated with control HIgG (N = 5), while the 2 µg dose also showed a marked decrease (32%), although it was not statistically significant. The treatment with chC13F12.1 (N = 5) gave as
    A statistically significant decrease of 88% and 51% resulted in the amount of splenic PC at the dose levels of 200 µg and 20 µg, respectively (Figure 5). No impact on the number of other subsets of B lymphocytes or T lymphocytes with chC12A3.2 and chC13F12.1 was observed (data not shown).
    Treatment with 200 µg of chC11D5.1 (N = 2) or chA7D12.2 (N = 1) resulted in a reduction of 89% and
    97%, respectively, in human PCs in the spleen, compared to control mice treated with HIgG (N = 5) (Figure 6). Treatment with chA7D12.1 also resulted in a 2.6-fold decrease in the amount of memory B cells with splenic human changes, compared to mice treated with HIgG (575 vs. 217 pcs / 105 HuCD45 + cells, for HIgG and chA7D12.1, respectively). Although BCMA could not be detected on the surface of memory B cells with changes in untreated humanized mice, it seems
    55 that while the BCMA level was below the detection limit by flow cytometry, it was sufficient to result in Ab-mediated elimination.
    To determine the impact of human PC depletion on serum human Ig levels in the HSC / NSG mice described above, subsets of human Ig were analyzed. Chimeric anti-BCMA mAbs
    17
    权利要求:
    Claims (1)
    [1]
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    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    US4522811A|1982-07-08|1985-06-11|Syntex Inc.|Serial injection of muramyldipeptides and liposomes enhances the anti-infective activity of muramyldipeptides|
    US5225539A|1986-03-27|1993-07-06|Medical Research Council|Recombinant altered antibodies and methods of making altered antibodies|
    US4946778A|1987-09-21|1990-08-07|Genex Corporation|Single polypeptide chain binding molecules|
    US5859205A|1989-12-21|1999-01-12|Celltech Limited|Humanised antibodies|
    US7018809B1|1991-09-19|2006-03-28|Genentech, Inc.|Expression of functional antibody fragments|
    US5736137A|1992-11-13|1998-04-07|Idec Pharmaceuticals Corporation|Therapeutic application of chimeric and radiolabeled antibodies to human B lymphocyte restricted differentiation antigen for treatment of B cell lymphoma|
    US20060067933A1|1999-01-07|2006-03-30|Gross Jane A|Soluble receptor BR43x2 and methods of using|
    EE05460B1|1999-01-07|2011-08-15|Zymogenetics, Inc.|Soluble receptor BR43x2 and methods for its use|
    US7833529B1|1999-01-07|2010-11-16|Zymogenetics, Inc.|Methods for inhibiting B lymphocyte proliferation with soluble ztnf4 receptor|
    US6475987B1|1999-05-06|2002-11-05|National Jewish Medical And Research Center|Tall-1 receptor homologues|
    NZ517782A|1999-08-17|2004-01-30|Biogen Inc|A beta-cell activating factor receptor belonging to the TNF family is used as a pharmaceutical agent and in the treatment of disease|
    AT329610T|2000-02-16|2006-07-15|Genentech Inc|ANTI-APRIL ANTIBODIES AND HYBRIDOMA CELLS|
    US20040002068A1|2000-03-01|2004-01-01|Corixa Corporation|Compositions and methods for the detection, diagnosis and therapy of hematological malignancies|
    US7371388B1|2000-05-04|2008-05-13|Human Genome Sciences, Inc.|Treatment of Sjogren's syndrome by administration of TR18 polypeptides|
    EE05411B1|2000-09-18|2011-04-15|Biogen, Inc.|Receptor nucleic acids and pol peptides|
    JP2004533997A|2001-02-20|2004-11-11|ザイモジェネティクス，インコーポレイティド|Antibodies that bind both BCMA and TACI|
    CU23007A1|2001-04-06|2004-12-17|Ct De Inmunologia Molecular Ct De Inmunologia Mole|IMMUNOTHERAPEUTIC COMBINATIONS FOR THE TREATMENT IMMUNOTHERAPEUTIC COMBINATIONS FOR THE TREATMENT OF TUMORS THAT OVER-EXPRESS GANGLIOSIDES TO OF TUMORS THAT OVER-EXPRESS GANGLOSIDES|
    WO2003013582A1|2001-08-06|2003-02-20|Genset S.A.|Genoxit agonists and antagonists for use in the treatment of metabolic disorders|
    US20080267965A1|2002-02-21|2008-10-30|Kalled Susan L|Use of Bcma as an Immunoregulatory Agent|
    EP3483183B1|2002-03-01|2021-04-21|Immunomedics, Inc.|Immunoconjugate comprising humanised rs7 antibodies|
    JP2006517785A|2002-10-29|2006-08-03|ジェネンテック・インコーポレーテッド|Novel compositions and methods for the treatment of immune related diseases|
    NZ543712A|2003-06-05|2008-06-30|Genentech Inc|Combination therapy for B cell disorders|
    US20050163775A1|2003-06-05|2005-07-28|Genentech, Inc.|Combination therapy for B cell disorders|
    US20090226440A1|2005-08-12|2009-09-10|Shane Grey|Prophylactic and/or Therapeutic Method for Treatment of Autoimmune Disease|
    JP5905184B2|2005-10-13|2016-04-20|ヒューマン ジノーム サイエンシーズ， インコーポレイテッドＨｕｍａｎ Ｇｅｎｏｍｅ Ｓｃｉｅｎｃｅｓ， Ｉｎｃ．|Methods and compositions for use in treating patients with autoantibody positive disease|
    DOP2006000277A|2005-12-12|2007-08-31|Bayer Pharmaceuticals Corp|ANTI MN ANTIBODIES AND METHODS FOR USE|
    JP2007309746A|2006-05-17|2007-11-29|Osaka Univ|Method of analyzing binding site of cell membrane surface substance|
    US20100074916A1|2006-10-10|2010-03-25|Government Of The United States Of America, As Represented By The Secretary, Dept. Of Health And|Avian influenza vaccine|EP2640750A1|2010-11-16|2013-09-25|Boehringer Ingelheim International GmbH|Agents and methods for treating diseases that correlate with bcma expression|
    US20130101599A1|2011-04-21|2013-04-25|Boehringer Ingelheim International Gmbh|Bcma-based stratification and therapy for multiplemyeloma patients|
    WO2012158818A2|2011-05-16|2012-11-22|Fabion Pharmaceuticals, Inc.|Multi-specific fab fusion proteins and methods of use|
    UA112434C2|2011-05-27|2016-09-12|Ґлаксо Ґруп Лімітед|ANTIGENCY BINDING SPECIFICALLY Binds to ALL|
    BR112013028779B8|2011-05-27|2021-04-20|Glaxo Group Ltd|antigen-binding protein or immunoconjugate, immunoconjugate, pharmaceutical composition, and, use of a composition|
    TWI679212B|2011-11-15|2019-12-11|美商安進股份有限公司|Binding molecules for e3 of bcma and cd3|
    CN104379179A|2012-04-11|2015-02-25|美国卫生和人力服务部|Chimeric antigen receptors targeting b-cell maturation antigen|
    US10189906B2|2012-11-01|2019-01-29|Max-Delrück-Centrum Für Molekulare Medizin|Antibody that binds CD269suitable for use in the treatment of plasma cell diseases such as multiple myeloma and autoimmune diseases|
    AU2013204922B2|2012-12-20|2015-05-14|Celgene Corporation|Chimeric antigen receptors|
    EP2762496A1|2013-02-05|2014-08-06|EngMab AG|Method for the selection of antibodies against BCMA|
    EP3620468A1|2013-02-05|2020-03-11|EngMab Sàrl|Method for the selection of antibodies against bcma|
    EP2762497A1|2013-02-05|2014-08-06|EngMab AG|Bispecific antibodies against CD3epsilon and BCMA|
    AR095374A1|2013-03-15|2015-10-14|Amgen ResGmbh|UNION MOLECULES FOR BCMA AND CD3|
    AU2014240083C1|2013-03-15|2019-10-24|Celgene Corporation|Modified T lymphocytes|
    KR102135006B1|2014-04-25|2020-07-17|블루버드 바이오, 인코포레이티드.|Mnd promoter chimeric antigen receptors|
    US10144782B2|2014-04-30|2018-12-04|Max-Delbrück-Centrum Für Molekulare Medizin In Der Helmholtz-Gemeinschaft|Humanized antibodies against CD269 |
    SG10201810723VA|2014-06-06|2018-12-28|Bluebird Bio Inc|Improved t cell compositions|
    SG11201700476VA|2014-07-21|2017-02-27|Novartis Ag|Treatment of cancer using humanized anti-bcma chimeric antigen receptor|
    SG11201700496WA|2014-07-22|2017-02-27|Cb Therapeutics Inc|Anti-pd-1 antibodies|
    BR112017001498A2|2014-07-24|2018-02-20|Bluebird Bio, Inc.|bcma chimeric antigen receptors|
    EP2982692A1|2014-08-04|2016-02-10|EngMab AG|Bispecific antibodies against CD3epsilon and BCMA|
    US10435470B2|2014-08-05|2019-10-08|Cb Therapeutics, Inc.|Anti-PD-L1 antibodies|
    EP3023437A1|2014-11-20|2016-05-25|EngMab AG|Bispecific antibodies against CD3epsilon and BCMA|
    EP3029068A1|2014-12-03|2016-06-08|EngMab AG|Bispecific antibodies against CD3epsilon and BCMA for use in the treatment of diseases|
    AU2015357533B2|2014-12-05|2021-10-07|Eureka Therapeutics, Inc.|Antibodies targeting B-cell maturation antigen and methods of use|
    EP3227432A4|2014-12-05|2018-08-22|Memorial Sloan Kettering Cancer Center|Chimeric antigen receptors targeting b-cell maturation antigen and uses thereof|
    MX2017007575A|2014-12-12|2018-03-01|Bluebird Bio Inc|Bcma chimeric antigen receptors.|
    ES2807591T3|2015-04-13|2021-02-23|Pfizer|Chimeric antigen receptors targeting B-cell maturation antigen|
    KR102110557B1|2015-04-13|2020-05-15|화이자 인코포레이티드|Therapeutic antibodies and uses thereof|
    EA202090931A3|2015-05-18|2020-10-30|Тср2 Терапьютикс Инк.|COMPOSITIONS AND METHODS FOR TCR REPROGRAMMING WITH HYBRID PROTEINS|
    RU2748655C2|2015-07-24|2021-05-28|Онкотрэкер, Инк.|Gamma-secretase inhibitors for treatment of immune system dysfunction|
    ES2777602T3|2015-08-03|2020-08-05|Engmab Sàrl|Monoclonal antibodies against human b-cell maturation antigen |
    HUE050556T2|2015-08-17|2020-12-28|Janssen Pharmaceutica Nv|Anti-bcma antibodies, bispecific antigen binding molecules that bind bcma and cd3, and uses thereof|
    WO2017058850A1|2015-09-28|2017-04-06|Regents Of The University Of Minnesota|Chimeric antigen receptort cells as therapeutic interventions for auto- and allo-immunity|
    JP6901493B2|2015-11-13|2021-07-14|アメリカ合衆国|Anti-BCMA polypeptides and proteins|
    CA3010019A1|2016-01-12|2017-07-20|James Richard BERENSON|Improved methods for monitoring immune status of a subject|
    AU2017216230A1|2016-02-03|2018-07-19|Amgen Inc.|BCMA and CD3 bispecific T cell engaging antibody constructs|
    EA201891753A1|2016-02-03|2019-01-31|Эмджен РисерчГмбх|BISPECIFIC CONSTRUCTIONS OF ANTIBODIES TO PSMA AND CD3, INVOLVING T-CELLS|
    KR20180107111A|2016-02-17|2018-10-01|시애틀 지네틱스, 인크.|BCMA antibodies and their uses for treating cancer and immunological disorders|
    US20200281973A1|2016-03-04|2020-09-10|Novartis Ag|Cells expressing multiple chimeric antigen receptormolecules and uses therefore|
    EP3430058A4|2016-03-15|2019-10-23|GeneronCorporation Ltd.|Multispecific fab fusion proteins and use thereof|
    SG10201912515XA|2016-04-01|2020-02-27|Kite Pharma Inc|Bcma binding molecules and methods of use thereof|
    MX2018012017A|2016-04-01|2019-07-04|Kite Pharma Inc|Chimeric antigen and t cell receptors and methods of use.|
    JP2019513370A|2016-04-01|2019-05-30|カイト ファーマ インコーポレイテッドＫｉｔｅ Ｐｈａ|Chimeric receptor and method of using the same|
    WO2018026953A1|2016-08-02|2018-02-08|TCR2 Therapeutics Inc.|Compositions and methods for tcr reprogramming using fusion proteins|
    AU2017341048A1|2016-10-07|2019-05-23|TCR2 Therapeutics Inc.|Compositions and methods for T-cell receptors reprogramming using fusion proteins|
    EA201990787A1|2016-11-02|2019-12-30|Энгмаб Сарл|SPECIFIC ANTIBODY TO BCMA AND CD3 AND IMMUNOLOGICAL MEDICINE FOR COMBINED USE IN TREATMENT OF MULTIPLE MYELOMA|
    RU2019122880A3|2016-12-21|2021-04-28|
    CN110582509A|2017-01-31|2019-12-17|诺华股份有限公司|Treatment of cancer using chimeric T cell receptor proteins with multispecific properties|
    RU2019128662A3|2017-02-17|2021-06-18|
    CA3051062A1|2017-02-28|2018-09-07|Affimed Gmbh|Tandem diabody for cd16a-directed nk-cell engagement|
    EP3604340A4|2017-03-24|2021-01-06|Zenyaku Kogyo Co., Ltd|ANTI-IgM/B CELL SURFACE ANTIGEN BISPECIFIC ANTIBODY|
    EP3615055A1|2017-04-28|2020-03-04|Novartis AG|Cells expressing a bcma-targeting chimeric antigen receptor, and combination therapy with a gamma secretase inhibitor|
    EP3615068A1|2017-04-28|2020-03-04|Novartis AG|Bcma-targeting agent, and combination therapy with a gamma secretase inhibitor|
    SG11201910143TA|2017-05-01|2019-11-28|Juno Therapeutics Inc|Combination of a cell therapy and an immunomodulatory compound|
    EP3638319A1|2017-06-14|2020-04-22|Dana-Farber Cancer Institute, Inc.|B-cell maturation antigen -directed nanoparticles|
    US20210147564A1|2017-06-20|2021-05-20|Teneobio, Inc.|Anti-bcma heavy chain-only antibodies|
    JP2020524000A|2017-06-20|2020-08-13|テネオワン， インコーポレイテッド|Anti-BCMA heavy chain only antibody|
    CN110997721A|2017-08-01|2020-04-10|免疫医疗有限责任公司|BCMA monoclonal antibody-drug conjugates|
    WO2019035938A1|2017-08-16|2019-02-21|Elstar Therapeutics, Inc.|Multispecific molecules that bind to bcma and uses thereof|
    BR112020004846A2|2017-09-13|2020-09-15|Teneobio, Inc.|heavy chain antibodies that bind to ectoenzymes|
    CA3076972A1|2017-09-29|2019-04-04|Mogam Institute For Biomedical Research|Anti-bcma antibody having high affinity for bcma and pharmaceutical composition for treatment of cancer, comprising same|
    EP3697436A1|2017-10-18|2020-08-26|Novartis AG|Compositions and methods for selective protein degradation|
    AU2018358067A1|2017-11-01|2020-05-07|Juno Therapeutics, Inc.|Antibodies and chimeric antigen receptors specific for B-cell maturation antigen|
    KR20200116077A|2017-11-01|2020-10-08|주노 쎄러퓨티크스 인코퍼레이티드|Chimeric antigen receptor and coding polynucleotide specific for B cell maturation antigen|
    BR112020008812A2|2017-11-06|2020-10-27|Juno Therapeutics Inc|combination of cell therapy and a gamma secretase inhibitor|
    WO2019099639A1|2017-11-15|2019-05-23|Navartis Ag|Bcma-targeting chimeric antigen receptor, cd19-targeting chimeric antigen receptor, and combination therapies|
    EP3717907A1|2017-11-30|2020-10-07|Novartis AG|Bcma-targeting chimeric antigen receptor, and uses thereof|
    JP2021505168A|2017-12-08|2021-02-18|ジュノー セラピューティクス インコーポレイテッド|Methods for Producing Manipulated T Cell Compositions|
    EP3720949A1|2017-12-08|2020-10-14|Juno Therapeutics, Inc.|Serum-free media formulation for culturing cells and methods of use thereof|
    US20210095022A1|2017-12-22|2021-04-01|TaneoBio, Inc.|Heavy chain antibodies binding to cd22|
    EP3737408A1|2018-01-08|2020-11-18|Novartis AG|Immune-enhancing rnas for combination with chimeric antigen receptor therapy|
    EP3746116A1|2018-01-31|2020-12-09|Novartis AG|Combination therapy using a chimeric antigen receptor|
    WO2019149250A1|2018-02-01|2019-08-08|南京驯鹿医疗技术有限公司|Chimeric antigen receptorbinding to bcma, and uses thereof|
    TW202138390A|2018-02-01|2021-10-16|大陸商信達生物製藥（蘇州）有限公司|Full-human anti-b cell mature antigensingle chain antibody and use thereof|
    EP3674328A4|2018-02-01|2021-11-24|Nanjing Iaso Biotherapeutics Co., Ltd.|Chimeric antigen receptorbinding to bcma, and uses thereof|
    WO2019160956A1|2018-02-13|2019-08-22|Novartis Ag|Chimeric antigen receptor therapy in combination with il-15r and il15|
    KR20210028140A|2018-03-02|2021-03-11|씨디알-라이프 아게|Trispecific antigen binding protein|
    CN113880952A|2018-04-13|2022-01-04|艾菲默德有限责任公司|Natural killer cell-conjugated antibody fusion constructs|
    WO2019226658A1|2018-05-21|2019-11-28|Compass Therapeutics Llc|Multispecific antigen-binding compositions and methods of use|
    WO2020004934A1|2018-06-26|2020-01-02|에이비엘바이오 주식회사|Anti-bcma antibody and use thereof|
    AU2019297451A1|2018-07-03|2021-01-28|Marengo Therapeutics, Inc.|Anti-TCR antibody molecules and uses thereof|
    CN112351997A|2018-07-20|2021-02-09|特尼奥生物股份有限公司|Heavy chain antibodies that bind to CD19|
    SG11202101204TA|2018-08-09|2021-03-30|Juno Therapeutics Inc|Processes for generating engineered cells and compositions thereof|
    CA3108698A1|2018-08-09|2020-02-13|Juno Therapeutics, Inc.|Methods for assessing integrated nucleic acids|
    CN112639083A|2018-08-31|2021-04-09|诺华股份有限公司|Method for producing cells expressing chimeric antigen receptor|
    WO2020047449A2|2018-08-31|2020-03-05|Novartis Ag|Methods of making chimeric antigen receptor-expressing cells|
    AU2019367218A1|2018-10-26|2021-06-03|Teneobio, Inc.|Heavy chain antibodies binding to CD38|
    WO2020089343A1|2018-10-31|2020-05-07|Juno Therapeutics Gmbh|Methods for selection and stimulation of cells and apparatus for same|
    SG11202104188VA|2018-11-01|2021-05-28|Juno Therapeutics Inc|Methods for treatment using chimeric antigen receptors specific for b-cell maturation antigen|
    EP3873937A2|2018-11-01|2021-09-08|Juno Therapeutics, Inc.|Chimeric antigen receptors specific for g protein-coupled receptor class c group 5 member d |
    US20220008477A1|2018-11-08|2022-01-13|Juno Therapeutics, Inc.|Methods and combinations for treatment and t cell modulation|
    RU2762942C1|2019-01-16|2021-12-24|Карибу Байосайенсиз, Инк.|Humanized antibody to bcma and bcma-car-t cells|
    CA3126087A1|2019-02-25|2020-09-03|Novartis Ag|Mesoporous silica particles compositions for viral delivery|
    EP3942025A1|2019-03-21|2022-01-26|Novartis AG|Car-t cell therapies with enhanced efficacy|
    KR20210149076A|2019-04-05|2021-12-08|테네오바이오, 인코포레이티드|Heavy chain antibody that binds PSMA|
    WO2020210678A1|2019-04-12|2020-10-15|Novartis Ag|Methods of making chimeric antigen receptor-expressing cells|
    WO2020219742A1|2019-04-24|2020-10-29|Novartis Ag|Compositions and methods for selective protein degradation|
    EP3964238A1|2019-05-07|2022-03-09|Gracell BiotechnologiesCo., Ltd.|Bcma-targeting engineered immune cell and use thereof|
    KR20220017914A|2019-05-07|2022-02-14|그라셀 바이오테크놀로지스컴퍼니, 리미티드|Engineered immune cells targeting BCMA and uses thereof|
    KR20220020810A|2019-06-14|2022-02-21|테네오바이오, 인코포레이티드|Multispecific heavy chain antibodies that bind to CD22 and CD3|
    WO2021022304A2|2019-07-30|2021-02-04|Qlsf Biotherapeutics, Inc.|MULTISPECIFIC BINDING COMPOUNDS THAT BIND TO LRRC15 AND CD3ε|
    WO2021018168A1|2019-07-30|2021-02-04|上海翰森生物医药科技有限公司|Anti-bcma antibody, antigen-binding fragment thereof and medical use thereof|
    CN112409482A|2019-08-20|2021-02-26|杭州尚健生物技术有限公司|BCMA antibodies|
    WO2021051390A1|2019-09-20|2021-03-25|上海吉倍生物技术有限公司|Bcma-targeted antibody and chimeric antigen receptor|
    WO2021108661A2|2019-11-26|2021-06-03|Novartis Ag|Chimeric antigen receptors and uses thereof|
    WO2021127489A1|2019-12-18|2021-06-24|Teneobio, Inc.|Heavy chain antibodies binding to cd38|
    WO2021132746A1|2019-12-24|2021-07-01|Abl Bio, Inc.|Anti-bcma/anti-4-1bb bispecific antibodies and uses thereof|
    KR20220012314A|2020-01-03|2022-02-03|살루브리스바이오테크 코., 리미티드|Antibodies that bind BCMA and uses thereof|
    CN111234020B|2020-01-23|2020-10-23|和铂医药有限公司|BCMA binding protein and preparation method and application thereof|
    WO2021154887A1|2020-01-28|2021-08-05|Juno Therapeutics, Inc.|Methods for t cell transduction|
    WO2021163389A1|2020-02-12|2021-08-19|Juno Therapeutics, Inc.|Bcma-directed chimeric antigen receptor t cell compositions and methods and uses thereof|
    CN113248611A|2020-02-13|2021-08-13|湖南华康恒健生物技术有限公司|anti-BCMA antibody, pharmaceutical composition and application thereof|
    WO2021173995A2|2020-02-27|2021-09-02|Novartis Ag|Methods of making chimeric antigen receptor-expressing cells|
    WO2021173985A2|2020-02-27|2021-09-02|Novartis Ag|Methods of making chimeric antigen receptor-expressing cells|
    WO2021207689A2|2020-04-10|2021-10-14|Juno Therapeutics, Inc.|Methods and uses related to cell therapy engineered with a chimeric antigen receptor targeting b-cell maturation antigen|
    WO2021222330A2|2020-04-28|2021-11-04|Juno Therapeutics, Inc.|Combination of bcma-directed t cell therapy and an immunomodulatory compound|
    US11186639B2|2020-04-29|2021-11-30|Teneoone, Inc.|Multispecific heavy chain antibodies with modified heavy chain constant regions|
    WO2021222578A1|2020-04-29|2021-11-04|Teneobio, Inc.|Multispecific heavy chain antibodies with modified heavy chain constant regions|
    WO2021228783A1|2020-05-11|2021-11-18|Janssen Pharmaceutica Nv|Methods for treating multiple myeloma|
    WO2021231657A1|2020-05-13|2021-11-18|Juno Therapeutics, Inc.|Methods of identifying features associated with clinical response and uses thereof|
    WO2021252920A1|2020-06-11|2021-12-16|Novartis Ag|Zbtb32 inhibitors and uses thereof|
    WO2022006316A1|2020-06-30|2022-01-06|Teneobio, Inc.|Multi-specific antibodies binding to bcma|
    WO2022040586A2|2020-08-21|2022-02-24|Novartis Ag|Compositions and methods for in vivo generation of car expressing cells|
    CN113024671A|2020-12-31|2021-06-25|北京艺妙神州医药科技有限公司|anti-BCMA antibody and application thereof|
    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    US15894209P| true| 2009-03-10|2009-03-10|
    US158942P|2009-03-10|
    US16292409P| true| 2009-03-24|2009-03-24|
    US162924P|2009-03-24|
    PCT/US2010/026825|WO2010104949A2|2009-03-10|2010-03-10|Anti-bcma antibodies|
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