CA2841738C - Combination therapy with an anti-cd19 antibody and a purine analog - Google Patents
Combination therapy with an anti-cd19 antibody and a purine analog Download PDFInfo
- Publication number
- CA2841738C CA2841738C CA2841738A CA2841738A CA2841738C CA 2841738 C CA2841738 C CA 2841738C CA 2841738 A CA2841738 A CA 2841738A CA 2841738 A CA2841738 A CA 2841738A CA 2841738 C CA2841738 C CA 2841738C
- Authority
- CA
- Canada
- Prior art keywords
- lymphoma
- seq
- sequence
- use according
- hodgkin
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 125000000561 purinyl group Chemical class N1=C(N=C2N=CNC2=C1)* 0.000 title abstract 2
- 238000002648 combination therapy Methods 0.000 title 1
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 claims abstract description 85
- 238000011282 treatment Methods 0.000 claims abstract description 74
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 claims abstract description 60
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 claims abstract description 38
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 claims abstract description 37
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 claims abstract description 35
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 claims abstract description 33
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 claims abstract description 32
- GIUYCYHIANZCFB-FJFJXFQQSA-N fludarabine phosphate Chemical compound C1=NC=2C(N)=NC(F)=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@@H]1O GIUYCYHIANZCFB-FJFJXFQQSA-N 0.000 claims description 93
- 229960000390 fludarabine Drugs 0.000 claims description 91
- 102100024222 B-lymphocyte antigen CD19 Human genes 0.000 claims description 69
- 101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 claims description 67
- 239000003814 drug Substances 0.000 claims description 21
- 238000001990 intravenous administration Methods 0.000 claims description 21
- 239000000203 mixture Substances 0.000 claims description 19
- 208000032839 leukemia Diseases 0.000 claims description 18
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims description 10
- 230000001154 acute effect Effects 0.000 claims description 8
- 208000011691 Burkitt lymphomas Diseases 0.000 claims description 7
- 201000003444 follicular lymphoma Diseases 0.000 claims description 7
- 239000011885 synergistic combination Substances 0.000 claims description 7
- 206010012818 diffuse large B-cell lymphoma Diseases 0.000 claims description 6
- 208000031671 Large B-Cell Diffuse Lymphoma Diseases 0.000 claims description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 230000001684 chronic effect Effects 0.000 claims description 2
- 238000009472 formulation Methods 0.000 claims 16
- 208000036170 B-Cell Marginal Zone Lymphoma Diseases 0.000 claims 4
- 201000003791 MALT lymphoma Diseases 0.000 claims 4
- 208000025205 Mantle-Cell Lymphoma Diseases 0.000 claims 4
- 201000007924 marginal zone B-cell lymphoma Diseases 0.000 claims 4
- 208000021937 marginal zone lymphoma Diseases 0.000 claims 4
- 238000004519 manufacturing process Methods 0.000 claims 2
- 210000004027 cell Anatomy 0.000 description 41
- 206010022000 influenza Diseases 0.000 description 39
- 206010028980 Neoplasm Diseases 0.000 description 24
- 150000003212 purines Chemical class 0.000 description 23
- 238000000034 method Methods 0.000 description 22
- 210000003719 b-lymphocyte Anatomy 0.000 description 21
- 241000282412 Homo Species 0.000 description 16
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 16
- 230000004083 survival effect Effects 0.000 description 15
- 230000000694 effects Effects 0.000 description 14
- 238000004364 calculation method Methods 0.000 description 13
- 230000004614 tumor growth Effects 0.000 description 13
- 229940079593 drug Drugs 0.000 description 12
- 238000001727 in vivo Methods 0.000 description 12
- 238000002474 experimental method Methods 0.000 description 11
- 230000002195 synergetic effect Effects 0.000 description 11
- 206010025323 Lymphomas Diseases 0.000 description 10
- 201000011510 cancer Diseases 0.000 description 10
- 201000010099 disease Diseases 0.000 description 10
- 102000004169 proteins and genes Human genes 0.000 description 10
- 108090000623 proteins and genes Proteins 0.000 description 10
- 238000011579 SCID mouse model Methods 0.000 description 9
- 230000004044 response Effects 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- 108010019670 Chimeric Antigen Receptors Proteins 0.000 description 8
- WYWHKKSPHMUBEB-UHFFFAOYSA-N tioguanine Chemical compound N1C(N)=NC(=S)C2=C1N=CN2 WYWHKKSPHMUBEB-UHFFFAOYSA-N 0.000 description 8
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 7
- 210000004369 blood Anatomy 0.000 description 7
- 239000008280 blood Substances 0.000 description 7
- 210000004698 lymphocyte Anatomy 0.000 description 7
- 125000003275 alpha amino acid group Chemical group 0.000 description 6
- 230000030833 cell death Effects 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 6
- 208000035475 disorder Diseases 0.000 description 6
- 230000005764 inhibitory process Effects 0.000 description 6
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 6
- 238000002560 therapeutic procedure Methods 0.000 description 6
- 241000699670 Mus sp. Species 0.000 description 5
- 210000001744 T-lymphocyte Anatomy 0.000 description 5
- 230000000996 additive effect Effects 0.000 description 5
- 229960004641 rituximab Drugs 0.000 description 5
- 206010006187 Breast cancer Diseases 0.000 description 4
- 208000026310 Breast neoplasm Diseases 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 230000008485 antagonism Effects 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 description 4
- 229960002170 azathioprine Drugs 0.000 description 4
- 230000027455 binding Effects 0.000 description 4
- 239000011230 binding agent Substances 0.000 description 4
- 210000001185 bone marrow Anatomy 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 238000013401 experimental design Methods 0.000 description 4
- 239000003112 inhibitor Substances 0.000 description 4
- 238000013507 mapping Methods 0.000 description 4
- 230000010534 mechanism of action Effects 0.000 description 4
- GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 description 4
- 229960001428 mercaptopurine Drugs 0.000 description 4
- 108090000765 processed proteins & peptides Proteins 0.000 description 4
- 102000004196 processed proteins & peptides Human genes 0.000 description 4
- 238000012552 review Methods 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 229960003087 tioguanine Drugs 0.000 description 4
- -1 CVID3 Proteins 0.000 description 3
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 3
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 3
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 3
- 150000001413 amino acids Chemical class 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 239000000427 antigen Substances 0.000 description 3
- 102000036639 antigens Human genes 0.000 description 3
- 108091007433 antigens Proteins 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 229960004397 cyclophosphamide Drugs 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 238000009169 immunotherapy Methods 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 238000011081 inoculation Methods 0.000 description 3
- 230000003993 interaction Effects 0.000 description 3
- 230000036210 malignancy Effects 0.000 description 3
- 230000003211 malignant effect Effects 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 230000002503 metabolic effect Effects 0.000 description 3
- 108020004707 nucleic acids Proteins 0.000 description 3
- 102000039446 nucleic acids Human genes 0.000 description 3
- 150000007523 nucleic acids Chemical class 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 208000037914 B-cell disorder Diseases 0.000 description 2
- 208000003950 B-cell lymphoma Diseases 0.000 description 2
- 101710117995 B-lymphocyte antigen CD19 Proteins 0.000 description 2
- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 description 2
- 230000006820 DNA synthesis Effects 0.000 description 2
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 2
- 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 description 2
- 239000007760 Iscove's Modified Dulbecco's Medium Substances 0.000 description 2
- 238000001793 Wilcoxon signed-rank test Methods 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 230000003042 antagnostic effect Effects 0.000 description 2
- 238000009175 antibody therapy Methods 0.000 description 2
- 230000022534 cell killing Effects 0.000 description 2
- 239000006285 cell suspension Substances 0.000 description 2
- 238000009096 combination chemotherapy Methods 0.000 description 2
- 238000011284 combination treatment Methods 0.000 description 2
- 231100000433 cytotoxic Toxicity 0.000 description 2
- 229940127089 cytotoxic agent Drugs 0.000 description 2
- 239000002254 cytotoxic agent Substances 0.000 description 2
- 231100000599 cytotoxic agent Toxicity 0.000 description 2
- 231100000135 cytotoxicity Toxicity 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 239000000890 drug combination Substances 0.000 description 2
- 239000012636 effector Substances 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000008029 eradication Effects 0.000 description 2
- 229960005304 fludarabine phosphate Drugs 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 230000002962 histologic effect Effects 0.000 description 2
- 238000002169 hydrotherapy Methods 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 238000011221 initial treatment Methods 0.000 description 2
- 230000002452 interceptive effect Effects 0.000 description 2
- 238000012417 linear regression Methods 0.000 description 2
- 210000003563 lymphoid tissue Anatomy 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 210000003519 mature b lymphocyte Anatomy 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 210000004877 mucosa Anatomy 0.000 description 2
- 239000007922 nasal spray Substances 0.000 description 2
- 210000004180 plasmocyte Anatomy 0.000 description 2
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 2
- 229960004618 prednisone Drugs 0.000 description 2
- 210000001948 pro-b lymphocyte Anatomy 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000004088 simulation Methods 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 238000002054 transplantation Methods 0.000 description 2
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 2
- 229960004528 vincristine Drugs 0.000 description 2
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 2
- 230000003442 weekly effect Effects 0.000 description 2
- OZFAFGSSMRRTDW-UHFFFAOYSA-N (2,4-dichlorophenyl) benzenesulfonate Chemical compound ClC1=CC(Cl)=CC=C1OS(=O)(=O)C1=CC=CC=C1 OZFAFGSSMRRTDW-UHFFFAOYSA-N 0.000 description 1
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- 206010000830 Acute leukaemia Diseases 0.000 description 1
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
- 229930024421 Adenine Natural products 0.000 description 1
- 240000000662 Anethum graveolens Species 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 208000025324 B-cell acute lymphoblastic leukemia Diseases 0.000 description 1
- 208000028564 B-cell non-Hodgkin lymphoma Diseases 0.000 description 1
- 241000208199 Buxus sempervirens Species 0.000 description 1
- 229940124292 CD20 monoclonal antibody Drugs 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 102000000844 Cell Surface Receptors Human genes 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 1
- 208000011231 Crohn disease Diseases 0.000 description 1
- 230000004543 DNA replication Effects 0.000 description 1
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 1
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical group [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
- 206010013710 Drug interaction Diseases 0.000 description 1
- 239000012591 Dulbecco’s Phosphate Buffered Saline Substances 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 208000017604 Hodgkin disease Diseases 0.000 description 1
- 101100383038 Homo sapiens CD19 gene Proteins 0.000 description 1
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 description 1
- 108010019476 Immunoglobulin Heavy Chains Proteins 0.000 description 1
- 102000013463 Immunoglobulin Light Chains Human genes 0.000 description 1
- 108010065825 Immunoglobulin Light Chains Proteins 0.000 description 1
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 208000034578 Multiple myelomas Diseases 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 208000007452 Plasmacytoma Diseases 0.000 description 1
- 208000033766 Prolymphocytic Leukemia Diseases 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 108010041388 Ribonucleotide Reductases Proteins 0.000 description 1
- 102000000505 Ribonucleotide Reductases Human genes 0.000 description 1
- 230000018199 S phase Effects 0.000 description 1
- 208000025317 T-cell and NK-cell neoplasm Diseases 0.000 description 1
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 1
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 210000005006 adaptive immune system Anatomy 0.000 description 1
- 229960000643 adenine Drugs 0.000 description 1
- 229940009456 adriamycin Drugs 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 230000000735 allogeneic effect Effects 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 230000000340 anti-metabolite Effects 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 229940100197 antimetabolite Drugs 0.000 description 1
- 239000002256 antimetabolite Substances 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000002449 bone cell Anatomy 0.000 description 1
- 210000002798 bone marrow cell Anatomy 0.000 description 1
- BQRGNLJZBFXNCZ-UHFFFAOYSA-N calcein am Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC(CN(CC(=O)OCOC(C)=O)CC(=O)OCOC(C)=O)=C(OC(C)=O)C=C1OC1=C2C=C(CN(CC(=O)OCOC(C)=O)CC(=O)OCOC(=O)C)C(OC(C)=O)=C1 BQRGNLJZBFXNCZ-UHFFFAOYSA-N 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000011712 cell development Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 229940044683 chemotherapy drug Drugs 0.000 description 1
- 208000018805 childhood acute lymphoblastic leukemia Diseases 0.000 description 1
- 108700010039 chimeric receptor Proteins 0.000 description 1
- 230000002301 combined effect Effects 0.000 description 1
- 238000012875 competitive assay Methods 0.000 description 1
- 238000004590 computer program Methods 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 229910052805 deuterium Inorganic materials 0.000 description 1
- 239000002532 enzyme inhibitor Substances 0.000 description 1
- 230000003325 follicular Effects 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 201000009277 hairy cell leukemia Diseases 0.000 description 1
- 230000028996 humoral immune response Effects 0.000 description 1
- 230000004727 humoral immunity Effects 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 210000003297 immature b lymphocyte Anatomy 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 238000010874 in vitro model Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000011396 initial chemotherapy Methods 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 229940079322 interferon Drugs 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 238000011418 maintenance treatment Methods 0.000 description 1
- 201000000638 mature B-cell neoplasm Diseases 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229940097496 nasal spray Drugs 0.000 description 1
- 208000010915 neoplasm of mature B-cells Diseases 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 238000012261 overproduction Methods 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 238000010837 poor prognosis Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- XJMOSONTPMZWPB-UHFFFAOYSA-M propidium iodide Chemical compound [I-].[I-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CCC[N+](C)(CC)CC)=C1C1=CC=CC=C1 XJMOSONTPMZWPB-UHFFFAOYSA-M 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 239000002213 purine nucleotide Substances 0.000 description 1
- 238000004445 quantitative analysis Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229940121503 tafasitamab Drugs 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 238000002424 x-ray crystallography Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
- A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
- A61K31/7076—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Immunology (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Molecular Biology (AREA)
- Epidemiology (AREA)
- Biochemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Endocrinology (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161523862P | 2011-08-16 | 2011-08-16 | |
| EP11177660.5 | 2011-08-16 | ||
| US61/523,862 | 2011-08-16 | ||
| EP11177660 | 2011-08-16 | ||
| PCT/EP2012/065904 WO2013024095A1 (en) | 2011-08-16 | 2012-08-14 | Combination therapy with an anti - cd19 antibody and a purine analog |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2841738A1 CA2841738A1 (en) | 2013-02-21 |
| CA2841738C true CA2841738C (en) | 2022-12-06 |
Family
ID=47714800
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2841738A Active CA2841738C (en) | 2011-08-16 | 2012-08-14 | Combination therapy with an anti-cd19 antibody and a purine analog |
Country Status (25)
| Country | Link |
|---|---|
| US (3) | US20140227277A1 (OSRAM) |
| EP (2) | EP2744826B1 (OSRAM) |
| JP (1) | JP6114273B2 (OSRAM) |
| KR (3) | KR102117202B1 (OSRAM) |
| CN (1) | CN103703027B (OSRAM) |
| AU (1) | AU2012296905B2 (OSRAM) |
| BR (1) | BR112013033916B1 (OSRAM) |
| CA (1) | CA2841738C (OSRAM) |
| CY (1) | CY1125148T1 (OSRAM) |
| DK (1) | DK2744826T3 (OSRAM) |
| ES (1) | ES2909720T3 (OSRAM) |
| HR (1) | HRP20220224T1 (OSRAM) |
| HU (1) | HUE058855T2 (OSRAM) |
| IL (1) | IL230295B (OSRAM) |
| LT (1) | LT2744826T (OSRAM) |
| MX (1) | MX353589B (OSRAM) |
| PL (1) | PL2744826T3 (OSRAM) |
| PT (1) | PT2744826T (OSRAM) |
| RS (1) | RS63121B1 (OSRAM) |
| RU (1) | RU2664462C9 (OSRAM) |
| SG (1) | SG10201606788VA (OSRAM) |
| SI (1) | SI2744826T1 (OSRAM) |
| SM (1) | SMT202200160T1 (OSRAM) |
| WO (1) | WO2013024095A1 (OSRAM) |
| ZA (1) | ZA201401835B (OSRAM) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2514591A (en) * | 2013-05-30 | 2014-12-03 | Mologen Ag | Predictive biomarker for cancer therapy |
| ES2523901B1 (es) * | 2013-05-31 | 2015-12-02 | Universidad Autónoma de Madrid | Uso de la deguelina como terapia suplementaria de la leucemia linfoide crónica |
| IL249533A0 (en) * | 2014-06-16 | 2017-02-28 | Xencor Inc | Treatment of chronic lymphocytic leukemia |
| US20170137516A1 (en) * | 2014-06-16 | 2017-05-18 | Xencor, Inc. | Treatment for chronic lymphocytic leukemia (cll) |
| US10617691B2 (en) * | 2015-05-26 | 2020-04-14 | Morphosys Ag | Combination of an anti-CD19 antibody and a Bruton's tyrosine kinase inhibitor and uses thereof |
| DK3337506T3 (da) | 2015-08-21 | 2021-09-06 | Morphosys Ag | Kombinationer og anvendelser deraf |
| SMT202100291T1 (it) * | 2016-05-30 | 2021-07-12 | Morphosys Ag | Metodi per prevedere il beneficio terapeutico di una terapia anti-cd19 in pazienti |
| SG10202104036QA (en) * | 2016-10-28 | 2021-05-28 | Morphosys Ag | Combination of anti cd19 antibody with a bcl-2 inhibitor and uses thereof |
| CA3062400A1 (en) | 2017-05-31 | 2018-12-06 | Morphosys Ag | Treatment paradigm for an anti-cd19 antibody and venetoclax combination treatment |
| CN110945028B (zh) | 2017-07-10 | 2023-09-08 | 国际药物发展生物技术公司 | 用非岩藻糖基化促凋亡抗cd19抗体与抗cd20抗体或化疗剂联合治疗b细胞恶性肿瘤 |
| KR20200030337A (ko) | 2018-09-12 | 2020-03-20 | 주식회사 녹십자랩셀 | 종양 치료를 위한 항-cd 19 항체 및 자연살해세포를 포함하는 약학적 조합물 |
| WO2020150513A1 (en) * | 2019-01-17 | 2020-07-23 | Fred Hutchinson Cancer Research Center | Methods to enhance the selectivity and effectiveness of cancer treatments |
| TW202334231A (zh) * | 2021-12-22 | 2023-09-01 | 德商莫菲西斯公司 | 抗cd19抗體療法的治療範例 |
| WO2025012080A1 (en) | 2023-07-13 | 2025-01-16 | Christian-Albrechts-Universität Zu Kiel | Humanized anti-cd7 antibody |
Family Cites Families (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11852A (en) | 1854-10-31 | Abraham bassford | ||
| US106A (en) | 1915-08-24 | Specipication | ||
| US4708871A (en) | 1983-03-08 | 1987-11-24 | Commonwealth Serum Laboratories Commission | Antigenically active amino acid sequences |
| US5686072A (en) | 1992-06-17 | 1997-11-11 | Board Of Regents, The University Of Texas | Epitope-specific monoclonal antibodies and immunotoxins and uses thereof |
| JP2002522511A (ja) * | 1998-08-11 | 2002-07-23 | アイデック ファーマスーティカルズ コーポレイション | 抗ｃｄ２０抗体の投与を含むｂ細胞リンパ腫の併用療法 |
| WO2000074718A1 (en) | 1999-06-09 | 2000-12-14 | Immunomedics, Inc. | Immunotherapy of autoimmune disorders using antibodies which target b-cells |
| CN1592645A (zh) | 2000-09-18 | 2005-03-09 | 拜奥根Idec公司 | 使用b细胞耗尽/免疫调节抗体组合治疗自身免疫病的联合疗法 |
| US7771951B2 (en) | 2001-12-03 | 2010-08-10 | Amgen Fremont Inc. | Antibody categorization based on binding characteristics |
| US20080260731A1 (en) * | 2002-03-01 | 2008-10-23 | Bernett Matthew J | Optimized antibodies that target cd19 |
| EP1648512A4 (en) | 2003-07-31 | 2009-01-21 | Immunomedics Inc | ANTI-CD19 ANTIBODIES |
| US7902338B2 (en) * | 2003-07-31 | 2011-03-08 | Immunomedics, Inc. | Anti-CD19 antibodies |
| US8444973B2 (en) | 2005-02-15 | 2013-05-21 | Duke University | Anti-CD19 antibodies and uses in B cell disorders |
| JP5215180B2 (ja) | 2005-06-20 | 2013-06-19 | メダレックス インコーポレーティッド | Ｃｄ１９抗体およびその使用法 |
| US20070136826A1 (en) * | 2005-12-02 | 2007-06-14 | Biogen Idec Inc. | Anti-mouse CD20 antibodies and uses thereof |
| ES2365046T3 (es) * | 2005-12-30 | 2011-09-21 | Merck Patent Gmbh | Anticuerpos anti-cd19 con inmunogenicidad reducida. |
| ME01786B (me) * | 2006-08-14 | 2014-09-20 | Xencor Inc | Optimizovana antitela usmerena na cd19 |
| CN103694349A (zh) | 2006-09-08 | 2014-04-02 | 米迪缪尼有限公司 | 人源化抗cd19抗体及其在治疗癌症、移植病和自身免疫病中的应用 |
| EP3392273A1 (en) | 2007-05-30 | 2018-10-24 | Xencor, Inc. | Methods and compositions for inhibiting cd32b expressing cells |
| CN101903403B (zh) | 2007-10-19 | 2016-03-16 | 西雅图基因公司 | Cd19结合剂及其应用 |
| WO2010095031A2 (en) | 2009-02-23 | 2010-08-26 | Glenmark Pharmaceuticals S.A. | Humanized antibodies that bind to cd19 and their uses |
| CA2765080C (en) | 2009-06-24 | 2018-07-17 | The Feinstein Institute For Medical Research | Methods for treating chronic lymphocytic leukemia |
| TWI409079B (zh) * | 2009-08-14 | 2013-09-21 | Roche Glycart Ag | 非典型岩藻醣化ｃｄ２０抗體與苯達莫斯汀（ｂｅｎｄａｍｕｓｔｉｎｅ）之組合療法 |
| AR077867A1 (es) * | 2009-08-14 | 2011-09-28 | Roche Glycart Ag | Terapia combinatoria de un anticuerpo cd20 afucosilado con fludarabina y/o mitoxantrona |
| WO2011057222A1 (en) * | 2009-11-06 | 2011-05-12 | Infinity Pharmaceuticals, Inc. | Oral formulations of a hedgehog pathway inhibitor |
-
2012
- 2012-08-14 HU HUE12745883A patent/HUE058855T2/hu unknown
- 2012-08-14 BR BR112013033916-0A patent/BR112013033916B1/pt active IP Right Grant
- 2012-08-14 DK DK12745883.4T patent/DK2744826T3/da active
- 2012-08-14 EP EP12745883.4A patent/EP2744826B1/en active Active
- 2012-08-14 SM SM20220160T patent/SMT202200160T1/it unknown
- 2012-08-14 ES ES12745883T patent/ES2909720T3/es active Active
- 2012-08-14 RS RS20220314A patent/RS63121B1/sr unknown
- 2012-08-14 CN CN201280036572.4A patent/CN103703027B/zh active Active
- 2012-08-14 KR KR1020197022418A patent/KR102117202B1/ko active Active
- 2012-08-14 KR KR1020207014644A patent/KR20200060779A/ko not_active Withdrawn
- 2012-08-14 HR HRP20220224TT patent/HRP20220224T1/hr unknown
- 2012-08-14 SI SI201231992T patent/SI2744826T1/sl unknown
- 2012-08-14 PL PL12745883T patent/PL2744826T3/pl unknown
- 2012-08-14 SG SG10201606788VA patent/SG10201606788VA/en unknown
- 2012-08-14 JP JP2014525432A patent/JP6114273B2/ja active Active
- 2012-08-14 PT PT127458834T patent/PT2744826T/pt unknown
- 2012-08-14 EP EP22155604.6A patent/EP4083071A3/en active Pending
- 2012-08-14 LT LTEPPCT/EP2012/065904T patent/LT2744826T/lt unknown
- 2012-08-14 MX MX2013014935A patent/MX353589B/es active IP Right Grant
- 2012-08-14 KR KR1020147006942A patent/KR20140071368A/ko not_active Ceased
- 2012-08-14 WO PCT/EP2012/065904 patent/WO2013024095A1/en not_active Ceased
- 2012-08-14 AU AU2012296905A patent/AU2012296905B2/en active Active
- 2012-08-14 CA CA2841738A patent/CA2841738C/en active Active
- 2012-08-14 RU RU2014103490A patent/RU2664462C9/ru active
- 2012-08-14 US US14/127,217 patent/US20140227277A1/en not_active Abandoned
-
2014
- 2014-01-02 IL IL230295A patent/IL230295B/en active IP Right Grant
- 2014-03-12 ZA ZA2014/01835A patent/ZA201401835B/en unknown
-
2020
- 2020-04-03 US US16/839,903 patent/US20200352975A1/en not_active Abandoned
-
2022
- 2022-04-14 CY CY20221100284T patent/CY1125148T1/el unknown
-
2024
- 2024-02-20 US US18/581,959 patent/US20240424012A1/en active Pending
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20240424012A1 (en) | Combinations and uses thereof | |
| US12194095B2 (en) | Combinations and uses thereof | |
| AU2012296905A1 (en) | Combination therapy with an anti - CD19 antibody and a purine analog | |
| EP2744515B1 (en) | Combination therapy with an anti-cd19 antibody and a nitrogen mustard | |
| JP2014525925A5 (OSRAM) | ||
| AU2012296907A1 (en) | Combination therapy with an anti - CD19 antibody and a nitrogen mustard | |
| HK40081594A (en) | Combination therapy with an anti-cd19 antibody and a nitrogen mustard | |
| HK40069168A (en) | Combinations and uses thereof | |
| NZ617771B2 (en) | Combination therapy with an anti - cd19 antibody and a purine analog | |
| HK1195322A (en) | Combination therapy with an anti-cd19 antibody and a purine analog | |
| HK1195322B (en) | Combination therapy with an anti-cd19 antibody and a purine analog |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20170726 |
|
| EEER | Examination request |
Effective date: 20170726 |
|
| EEER | Examination request |
Effective date: 20170726 |
|
| EEER | Examination request |
Effective date: 20170726 |
|
| EEER | Examination request |
Effective date: 20170726 |