JP2012510461A - Cd38を特異的に認識する抗体およびメルファランを含有する抗腫瘍性組合せ剤 - Google Patents
Cd38を特異的に認識する抗体およびメルファランを含有する抗腫瘍性組合せ剤 Download PDFInfo
- Publication number
- JP2012510461A JP2012510461A JP2011538092A JP2011538092A JP2012510461A JP 2012510461 A JP2012510461 A JP 2012510461A JP 2011538092 A JP2011538092 A JP 2011538092A JP 2011538092 A JP2011538092 A JP 2011538092A JP 2012510461 A JP2012510461 A JP 2012510461A
- Authority
- JP
- Japan
- Prior art keywords
- seq
- amino acid
- antibody
- nos
- acid sequence
- 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.)
- Withdrawn
Links
- SGDBTWWWUNNDEQ-LBPRGKRZSA-N melphalan Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N(CCCl)CCCl)C=C1 SGDBTWWWUNNDEQ-LBPRGKRZSA-N 0.000 title claims abstract description 36
- 229960001924 melphalan Drugs 0.000 title claims abstract description 33
- 102100031585 ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Human genes 0.000 title claims abstract description 18
- 101000777636 Homo sapiens ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Proteins 0.000 title claims abstract description 18
- 230000000259 anti-tumor effect Effects 0.000 title description 7
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 53
- 206010028980 Neoplasm Diseases 0.000 claims description 39
- 108010047041 Complementarity Determining Regions Proteins 0.000 claims description 33
- 239000003814 drug Substances 0.000 claims description 11
- 201000011510 cancer Diseases 0.000 claims description 8
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 claims description 5
- 230000004540 complement-dependent cytotoxicity Effects 0.000 claims description 5
- 230000006907 apoptotic process Effects 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 3
- 210000004027 cell Anatomy 0.000 description 13
- 238000002347 injection Methods 0.000 description 13
- 239000007924 injection Substances 0.000 description 13
- 238000011282 treatment Methods 0.000 description 13
- 230000022534 cell killing Effects 0.000 description 11
- 241001465754 Metazoa Species 0.000 description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- 238000000034 method Methods 0.000 description 10
- 229940079593 drug Drugs 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- 239000000203 mixture Substances 0.000 description 8
- 230000001225 therapeutic effect Effects 0.000 description 8
- 239000007864 aqueous solution Substances 0.000 description 7
- 230000034994 death Effects 0.000 description 7
- 239000012634 fragment Substances 0.000 description 7
- 241000699670 Mus sp. Species 0.000 description 6
- 231100000419 toxicity Toxicity 0.000 description 6
- 230000001988 toxicity Effects 0.000 description 6
- 206010035226 Plasma cell myeloma Diseases 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 230000004580 weight loss Effects 0.000 description 5
- 208000034578 Multiple myelomas Diseases 0.000 description 4
- 241000699666 Mus <mouse, genus> Species 0.000 description 4
- 230000030833 cell death Effects 0.000 description 4
- 208000032839 leukemia Diseases 0.000 description 4
- 231100000956 nontoxicity Toxicity 0.000 description 4
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 4
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 4
- 229920000053 polysorbate 80 Polymers 0.000 description 4
- 229940068968 polysorbate 80 Drugs 0.000 description 4
- 230000004614 tumor growth Effects 0.000 description 4
- BQOHYSXSASDCEA-KEOHHSTQSA-N Cyclic ADP-Ribose Chemical compound C([C@@H]1[C@H]([C@H]([C@@H](O1)N1C=2N=CN3C(C=2N=C1)=N)O)O)OP(O)(=O)OP(O)(=O)OC[C@@H]1[C@@H](O)[C@@H](O)[C@H]3O1 BQOHYSXSASDCEA-KEOHHSTQSA-N 0.000 description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
- 230000001154 acute effect Effects 0.000 description 3
- 229940100198 alkylating agent Drugs 0.000 description 3
- 239000002168 alkylating agent Substances 0.000 description 3
- 239000002246 antineoplastic agent Substances 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- 201000005787 hematologic cancer Diseases 0.000 description 3
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 description 3
- 238000002513 implantation Methods 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 201000001441 melanoma Diseases 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 201000009030 Carcinoma Diseases 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 238000011579 SCID mouse model Methods 0.000 description 2
- 239000000427 antigen Substances 0.000 description 2
- 102000036639 antigens Human genes 0.000 description 2
- 108091007433 antigens Proteins 0.000 description 2
- 239000007900 aqueous suspension Substances 0.000 description 2
- 230000001588 bifunctional effect Effects 0.000 description 2
- 238000004364 calculation method Methods 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000002512 chemotherapy Methods 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 230000009260 cross reactivity Effects 0.000 description 2
- 230000003111 delayed effect Effects 0.000 description 2
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 2
- 230000005847 immunogenicity Effects 0.000 description 2
- 231100000682 maximum tolerated dose Toxicity 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 239000002953 phosphate buffered saline Substances 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 210000002536 stromal cell Anatomy 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 230000002195 synergetic effect Effects 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 238000002054 transplantation Methods 0.000 description 2
- PWJFNRJRHXWEPT-UHFFFAOYSA-N ADP ribose Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(=O)OCC(O)C(O)C(O)C=O)C(O)C1O PWJFNRJRHXWEPT-UHFFFAOYSA-N 0.000 description 1
- SRNWOUGRCWSEMX-KEOHHSTQSA-N ADP-beta-D-ribose Chemical compound C([C@H]1O[C@H]([C@@H]([C@@H]1O)O)N1C=2N=CN=C(C=2N=C1)N)OP(O)(=O)OP(O)(=O)OC[C@H]1O[C@@H](O)[C@H](O)[C@@H]1O SRNWOUGRCWSEMX-KEOHHSTQSA-N 0.000 description 1
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 1
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 1
- 208000036762 Acute promyelocytic leukaemia Diseases 0.000 description 1
- 208000003950 B-cell lymphoma Diseases 0.000 description 1
- 208000011691 Burkitt lymphomas Diseases 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 201000008808 Fibrosarcoma Diseases 0.000 description 1
- 208000032612 Glial tumor Diseases 0.000 description 1
- 206010018338 Glioma Diseases 0.000 description 1
- 101000633786 Homo sapiens SLAM family member 6 Proteins 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 1
- 102000008394 Immunoglobulin Fragments Human genes 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
- 206010023347 Keratoacanthoma Diseases 0.000 description 1
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 108091007491 NSP3 Papain-like protease domains Proteins 0.000 description 1
- 206010029260 Neuroblastoma Diseases 0.000 description 1
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 1
- 102100029197 SLAM family member 6 Human genes 0.000 description 1
- 206010042971 T-cell lymphoma Diseases 0.000 description 1
- 208000027585 T-cell non-Hodgkin lymphoma Diseases 0.000 description 1
- 102100023935 Transmembrane glycoprotein NMB Human genes 0.000 description 1
- 201000006083 Xeroderma Pigmentosum Diseases 0.000 description 1
- 208000009956 adenocarcinoma Diseases 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 229940098174 alkeran Drugs 0.000 description 1
- 238000011394 anticancer treatment Methods 0.000 description 1
- 230000001640 apoptogenic effect Effects 0.000 description 1
- 210000001130 astrocyte Anatomy 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 239000003560 cancer drug Substances 0.000 description 1
- 125000005626 carbonium group Chemical group 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 210000003679 cervix uteri Anatomy 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 229940044683 chemotherapy drug Drugs 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 208000035250 cutaneous malignant susceptibility to 1 melanoma Diseases 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 230000010013 cytotoxic mechanism Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 208000010932 epithelial neoplasm Diseases 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 210000003128 head Anatomy 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 210000004408 hybridoma Anatomy 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000006882 induction of apoptosis Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 230000000527 lymphocytic effect Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 229960004961 mechlorethamine Drugs 0.000 description 1
- HAWPXGHAZFHHAD-UHFFFAOYSA-N mechlorethamine Chemical class ClCCN(C)CCCl HAWPXGHAZFHHAD-UHFFFAOYSA-N 0.000 description 1
- 238000000302 molecular modelling Methods 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- 201000000050 myeloid neoplasm Diseases 0.000 description 1
- 210000003739 neck Anatomy 0.000 description 1
- 230000001613 neoplastic effect Effects 0.000 description 1
- 208000007538 neurilemmoma Diseases 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 150000002895 organic esters Chemical class 0.000 description 1
- 201000008968 osteosarcoma Diseases 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 210000001428 peripheral nervous system Anatomy 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 238000002823 phage display Methods 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 150000002993 phenylalanine derivatives Chemical class 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 201000009410 rhabdomyosarcoma Diseases 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 206010039667 schwannoma Diseases 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 206010041823 squamous cell carcinoma Diseases 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- 208000001608 teratocarcinoma Diseases 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 210000001685 thyroid gland Anatomy 0.000 description 1
- 108091007466 transmembrane glycoproteins Proteins 0.000 description 1
- 210000003932 urinary bladder Anatomy 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
Classifications
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
- A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
-
- 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
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Peptides Or Proteins (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Description
log10細胞死滅=T−C(日数)/3.32×Td
式中、T−Cは腫瘍増殖の遅延を表し、腫瘍があらかじめ定めた値(例えば、1g)に達するまでの日数の、治療群についての中央値(T)および対照群についての中央値(C)であり、Tdは、対照動物で腫瘍体積が2倍になるのに必要な日数を表す[T.H.Corbett et al.,Cancer,40:2660−2680 (1977);F.M.Schabel et al.,Cancer Drug Development,Part B,Methods in Cancer Research,17:3−51,NewYork,Academic Press Inc.(1979)]。log10細胞死滅が0.7以上であれば、この完成品は活性であると判断される。log10細胞死滅が2.8より大きければ、この完成品は非常に活性が高いと判断される。
0日目、実験に供される動物(一般にマウス)に、腫瘍断片30から60mgを両側に皮下移植する。腫瘍を持たされた動物を、この腫瘍の大きさに関して無作為に割り振って様々な治療と対照に供する。移植後、腫瘍があらかじめ定めた大きさに到達したら、腫瘍の種類に依存して、化学療法を開始し、動物を毎日観察する。治療中、それぞれの動物群の重さを、重さの減少が最大になり、続いて重さが完全に回復するまで、毎日測定する。次いで、試験終了まで、動物群の重さを週に1回か2回測定する。腫瘍は、約2gに達するか動物が死亡する(腫瘍が2gに達する前にそうなってしまった場合)まで、腫瘍が2倍になる時間に依存して、週に1回から5回測定する。動物を、安楽死即ち死後直ちに死体解剖する。
・≧20%体重減少または≧10%薬物死を誘導する投薬量では毒性であるとした、
・log10細胞死滅=(T−C)/[3.32×(腫瘍が2倍になる日数)]を計算することにより抗腫瘍効力を求めた
(Tは、処置したマウスで1000mgに達するまでの時間の中央値を意味し、Cは対照マウスで同じ大きさに達するまでの時間の中央値(25.3日)を意味する;無再発生存個体はこれらの計算から排除し別々に集計する。)。log細胞死滅<0.7では抗腫瘍活性はないものとした。log細胞死滅≧2.8では治療は非常に活性が高いものとした
・無再発生存個体(TFS):研究の全期間(最後の処置から100日後以降)について触診限界(63mg)未満の完全回復に相当する。
・治療的相乗作用:ある組合せ剤が研究の最良の薬剤単独よりも活性が高い(少なくとも1のlog細胞死滅の差)ならばこの組合せ剤は治療的相乗作用を有する。
・≧20%体重減少または≧10%薬物死を誘導する投薬量では毒性であるとした、
・log10細胞死滅=(T−C)/[3.32×(腫瘍が2倍になる日数)]を計算することにより抗腫瘍効力を求めた
(Tは、処置したマウスで1000mgに達するまでの時間の中央値を意味し、Cは対照マウスで同じ大きさに達するまでの時間の中央値(16.8日)を意味する;無再発生存個体はこれらの計算から排除し別々に集計する。)。log細胞死滅<0.7では抗腫瘍活性はないものとした。log細胞死滅≧2.8では治療は非常に活性が高いものとした
・治療的相乗作用:ある組合せ剤が研究の最良の薬剤単独よりも活性が高い(少なくとも1のlog細胞死滅の差)ならばこの組合せ剤は治療的相乗作用を有する。
Claims (10)
- アポトーシス、抗体依存性細胞媒介性細胞傷害(ADCC)、および補体依存性細胞傷害(CDC)により、CD38+細胞を死滅させることができる、CD38を特異的に認識する抗体、および少なくともメルファランを含む薬学的組合せ剤。
- 抗体がヒト化抗体である、請求項1に記載の組合せ剤。
- 前記抗体が、配列番号:1、2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、24、25、26、27、28、29、30、31、32、33、34、35、および36からなる群より選択されるアミノ酸配列を有する相補性決定領域を1つ以上含む、請求項2に記載の組合せ剤。
- 前記抗体が、少なくとも1本の重鎖および少なくとも1本の軽鎖を含み、前記重鎖は配列番号66で表されるアミノ酸配列を有するとともに前記重鎖は配列番号:13、14、および15で表されるアミノ酸配列を有する3つの連続した相補性決定領域を含み、ならびに前記軽鎖は配列番号:62および64からなる群より選択されるアミノ酸配列を有するとともに軽鎖は配列番号:16、17、および18で表されるアミノ酸配列を有する3つの連続した相補性決定領域を含む、請求項3に記載の組合せ剤。
- 前記抗体が、少なくとも1本の重鎖および少なくとも1本の軽鎖を含み、前記重鎖は配列番号72で表されるアミノ酸配列を有するとともに重鎖は配列番号:25、26、および27で表されるアミノ酸配列を有する3つの連続した相補性決定領域を含み、ならびに前記軽鎖は配列番号:68および70からなる群より選択されるアミノ酸配列を有するとともに軽鎖は配列番号:28、29、および30で表されるアミノ酸配列を有する3つの連続した相補性決定領域を含む、請求項3に記載の組合せ剤。
- 癌治療用医薬を製造するための請求項1に記載の薬学的組合せ剤を調製するためのCD38を特異的に認識する抗体の使用。
- 抗体がヒト化抗体である、請求項6に記載の使用。
- 前記抗体が、配列番号:1、2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、24、25、26、27、28、29、30、31、32、33、34、35、および36からなる群より選択されるアミノ酸配列を有する相補性決定領域を1つ以上含む、請求項7に記載の使用。
- 前記抗体が、少なくとも1本の重鎖および少なくとも1本の軽鎖を含み、前記重鎖は配列番号66で表されるアミノ酸配列を有するとともに重鎖は配列番号:13、14、および15で表されるアミノ酸配列を有する3つの連続した相補性決定領域を含み、ならびに前記軽鎖は配列番号:62および64からなる群より選択されるアミノ酸配列を有するとともに軽鎖は配列番号:16、17、および18で表されるアミノ酸配列を有する3つの連続した相補性決定領域を含む、請求項8に記載の使用。
- 前記抗体が、少なくとも1本の重鎖および少なくとも1本の軽鎖を含み、前記重鎖は配列番号72で表されるアミノ酸配列を有するとともに前記重鎖は配列番号:25、26、および27で表されるアミノ酸配列を有する3つの連続した相補性決定領域を含み、ならびに前記軽鎖は配列番号:68および70からなる群より選択されるアミノ酸配列を有するとともに軽鎖は配列番号:28、29、および30で表されるアミノ酸配列を有する3つの連続した相補性決定領域を含む、請求項8に記載の使用。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP08291116.5 | 2008-11-28 | ||
EP08291116A EP2191840A1 (en) | 2008-11-28 | 2008-11-28 | Antitumor combinations containing antibodies recognizing specifically CD38 and melphalan |
PCT/IB2009/055389 WO2010061357A1 (en) | 2008-11-28 | 2009-11-27 | Antitumor combinations containing antibodies recognizing specifically cd38 and melphalan |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2015107404A Division JP6148696B2 (ja) | 2008-11-28 | 2015-05-27 | Cd38を特異的に認識する抗体およびメルファランを含有する抗腫瘍性組合せ剤 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2012510461A true JP2012510461A (ja) | 2012-05-10 |
JP2012510461A5 JP2012510461A5 (ja) | 2012-11-22 |
Family
ID=40578382
Family Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2011538092A Withdrawn JP2012510461A (ja) | 2008-11-28 | 2009-11-27 | Cd38を特異的に認識する抗体およびメルファランを含有する抗腫瘍性組合せ剤 |
JP2015107404A Active JP6148696B2 (ja) | 2008-11-28 | 2015-05-27 | Cd38を特異的に認識する抗体およびメルファランを含有する抗腫瘍性組合せ剤 |
JP2017037860A Pending JP2017141233A (ja) | 2008-11-28 | 2017-03-01 | Cd38を特異的に認識する抗体およびメルファランを含有する抗腫瘍性組合せ剤 |
Family Applications After (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2015107404A Active JP6148696B2 (ja) | 2008-11-28 | 2015-05-27 | Cd38を特異的に認識する抗体およびメルファランを含有する抗腫瘍性組合せ剤 |
JP2017037860A Pending JP2017141233A (ja) | 2008-11-28 | 2017-03-01 | Cd38を特異的に認識する抗体およびメルファランを含有する抗腫瘍性組合せ剤 |
Country Status (33)
Country | Link |
---|---|
US (1) | US9259406B2 (ja) |
EP (2) | EP2191840A1 (ja) |
JP (3) | JP2012510461A (ja) |
KR (1) | KR101733252B1 (ja) |
CN (1) | CN102264385B (ja) |
AR (1) | AR074219A1 (ja) |
AU (1) | AU2009321249B2 (ja) |
BR (1) | BRPI0921864B1 (ja) |
CA (1) | CA2744990C (ja) |
CL (1) | CL2011001254A1 (ja) |
CO (1) | CO6440557A2 (ja) |
CR (1) | CR20110280A (ja) |
EA (1) | EA026867B1 (ja) |
EC (1) | ECSP11011062A (ja) |
HK (1) | HK1164165A1 (ja) |
HN (1) | HN2011001417A (ja) |
IL (1) | IL213116B (ja) |
MA (1) | MA32896B1 (ja) |
ME (1) | ME01136B (ja) |
MX (1) | MX342625B (ja) |
MY (1) | MY164577A (ja) |
NI (1) | NI201100105A (ja) |
NZ (1) | NZ593027A (ja) |
PA (1) | PA8850101A1 (ja) |
PE (1) | PE20120340A1 (ja) |
SG (1) | SG171820A1 (ja) |
SV (1) | SV2011003924A (ja) |
TN (1) | TN2011000232A1 (ja) |
TW (1) | TWI454260B (ja) |
UA (1) | UA107069C2 (ja) |
UY (1) | UY32263A (ja) |
WO (1) | WO2010061357A1 (ja) |
ZA (1) | ZA201103925B (ja) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2015530399A (ja) * | 2012-09-25 | 2015-10-15 | モルフォシス エージー | 組み合わせ及びその使用 |
Families Citing this family (41)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP2191840A1 (en) | 2008-11-28 | 2010-06-02 | Sanofi-Aventis | Antitumor combinations containing antibodies recognizing specifically CD38 and melphalan |
WO2011130624A2 (en) | 2010-04-16 | 2011-10-20 | Immune Disease Institute, Inc. | Sustained polypeptide expression from synthetic, modified rnas and uses thereof |
WO2012019168A2 (en) | 2010-08-06 | 2012-02-09 | Moderna Therapeutics, Inc. | Engineered nucleic acids and methods of use thereof |
HUE031956T2 (en) | 2010-09-27 | 2017-08-28 | Morphosys Ag | Anti-CD38 antibody and lenalidomide or bortezomib for the treatment of multiple myeloma and NHL |
DE19177059T1 (de) | 2010-10-01 | 2021-10-07 | Modernatx, Inc. | N1-methyl-pseudouracile enthältendes ribonucleinsäuren sowie ihre verwendungen |
UA112170C2 (uk) * | 2010-12-10 | 2016-08-10 | Санофі | Протипухлинна комбінація, що містить антитіло, яке специфічно розпізнає cd38, і бортезоміб |
JOP20210044A1 (ar) | 2010-12-30 | 2017-06-16 | Takeda Pharmaceuticals Co | الأجسام المضادة لـ cd38 |
DE12722942T1 (de) | 2011-03-31 | 2021-09-30 | Modernatx, Inc. | Freisetzung und formulierung von manipulierten nukleinsäuren |
US9464124B2 (en) | 2011-09-12 | 2016-10-11 | Moderna Therapeutics, Inc. | Engineered nucleic acids and methods of use thereof |
JP6113737B2 (ja) | 2011-10-03 | 2017-04-12 | モデルナティエックス インコーポレイテッドModernaTX,Inc. | 修飾型のヌクレオシド、ヌクレオチドおよび核酸、ならびにそれらの使用方法 |
MX2014007233A (es) | 2011-12-16 | 2015-02-04 | Moderna Therapeutics Inc | Composiciones de nucleosidos, nucleotidos y acidos nucleicos modificados. |
US9283287B2 (en) | 2012-04-02 | 2016-03-15 | Moderna Therapeutics, Inc. | Modified polynucleotides for the production of nuclear proteins |
US10501512B2 (en) | 2012-04-02 | 2019-12-10 | Modernatx, Inc. | Modified polynucleotides |
EP2834259A4 (en) | 2012-04-02 | 2016-08-24 | Moderna Therapeutics Inc | MODIFIED POLYNUCLEOTIDES |
US9572897B2 (en) | 2012-04-02 | 2017-02-21 | Modernatx, Inc. | Modified polynucleotides for the production of cytoplasmic and cytoskeletal proteins |
CA2892529C (en) | 2012-11-26 | 2023-04-25 | Moderna Therapeutics, Inc. | Terminally modified rna |
UA118255C2 (uk) * | 2012-12-07 | 2018-12-26 | Санофі | Композиція, яка містить антитіло до cd38 і леналідомід |
US10342869B2 (en) | 2012-12-07 | 2019-07-09 | The Regents Of The University Of California | Compositions comprising anti-CD38 antibodies and lenalidomide |
US8980864B2 (en) | 2013-03-15 | 2015-03-17 | Moderna Therapeutics, Inc. | Compositions and methods of altering cholesterol levels |
WO2015048744A2 (en) | 2013-09-30 | 2015-04-02 | Moderna Therapeutics, Inc. | Polynucleotides encoding immune modulating polypeptides |
CA2926218A1 (en) | 2013-10-03 | 2015-04-09 | Moderna Therapeutics, Inc. | Polynucleotides encoding low density lipoprotein receptor |
US20150118251A1 (en) | 2013-10-31 | 2015-04-30 | Sanofi | Specific anti-cd38 antibodies for treating human cancers |
US9603927B2 (en) | 2014-02-28 | 2017-03-28 | Janssen Biotech, Inc. | Combination therapies with anti-CD38 antibodies |
US9732154B2 (en) | 2014-02-28 | 2017-08-15 | Janssen Biotech, Inc. | Anti-CD38 antibodies for treatment of acute lymphoblastic leukemia |
US10617757B2 (en) | 2014-08-08 | 2020-04-14 | The Regents Of The University Of California | Methods for treating multiple myeloma |
ES2890669T3 (es) | 2014-09-09 | 2022-01-21 | Janssen Biotech Inc | Terapias de combinación con anticuerpos anti-CD38 |
KR102597989B1 (ko) | 2014-12-04 | 2023-11-02 | 얀센 바이오테크 인코포레이티드 | 급성 골수성 백혈병을 치료하기 위한 항-cd38 항체 |
US10766965B2 (en) | 2015-05-20 | 2020-09-08 | Janssen Biotech, Inc. | Anti-CD38 antibodies for treatment of light chain amyloidosis and other CD38-positive hematological malignancies |
CR20170587A (es) | 2015-06-22 | 2018-04-03 | Janssen Biotech Inc | Terapias de combinación para enfermedades malignas hematológicas con anticuerpos anti-cd38 e inhibidores de survivina |
US20170044265A1 (en) | 2015-06-24 | 2017-02-16 | Janssen Biotech, Inc. | Immune Modulation and Treatment of Solid Tumors with Antibodies that Specifically Bind CD38 |
US10781261B2 (en) | 2015-11-03 | 2020-09-22 | Janssen Biotech, Inc. | Subcutaneous formulations of anti-CD38 antibodies and their uses |
WO2017079150A1 (en) | 2015-11-03 | 2017-05-11 | Janssen Biotech, Inc. | Subcutaneous formulations of anti-cd38 antibodies and their uses |
WO2019035938A1 (en) | 2017-08-16 | 2019-02-21 | Elstar Therapeutics, Inc. | MULTISPECIFIC MOLECULES BINDING TO BCMA AND USES THEREOF |
AU2018359527A1 (en) | 2017-10-31 | 2020-05-07 | Janssen Biotech, Inc. | Methods of treating high risk multiple myeloma |
WO2019130228A1 (en) * | 2018-01-01 | 2019-07-04 | Orbicular Pharmaceutical Technologies Pvt. Ltd., | Stable liquid compositions of melphalan |
CN113574071A (zh) | 2019-03-15 | 2021-10-29 | 莫佛塞斯公司 | 用于治疗自身抗体介导的自身免疫疾病的抗-cd38抗体及其药物组合物 |
US11655302B2 (en) | 2019-06-10 | 2023-05-23 | Sanofi | Anti-CD38 antibodies and formulations |
EP4069743A1 (en) | 2019-12-05 | 2022-10-12 | Sanofi-Aventis U.S. LLC | Formulations of anti-cd38 antibodies for subcutaneous administration |
AU2022208200A1 (en) | 2021-01-14 | 2023-07-20 | Morphosys Ag | Anti-cd38 antibodies and their uses |
TW202302642A (zh) | 2021-03-01 | 2023-01-16 | 德商莫菲西斯公司 | 用於治療抗體介導移植物排斥用途之抗cd38抗體 |
TW202321303A (zh) | 2021-07-19 | 2023-06-01 | 德商莫菲西斯公司 | 抗pla2r自體抗體媒介膜性腎病變之治療 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2003524587A (ja) * | 1998-06-05 | 2003-08-19 | マヨ ファウンデーション フォー メディカル エデュケーション アンド リサーチ | 多発性骨髄腫を処置するための、cd38に対する、遺伝子操作した抗体の使用 |
WO2008047242A2 (en) * | 2006-10-19 | 2008-04-24 | Sanofi-Aventis | Novel anti-cd38 antibodies for the treatment of cancer |
JP2008533977A (ja) * | 2005-03-23 | 2008-08-28 | ゲンマブ エー/エス | 多発性骨髄腫の治療のためのcd38に対する抗体 |
Family Cites Families (28)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB750155A (en) | 1953-03-17 | 1956-06-13 | Nat Res Dev | Substituted alanines |
US3032585A (en) | 1954-12-03 | 1962-05-01 | Nat Res Dev | Process for the production of p-bis-(2-chloroethyl)-aminophenylalanine |
US4444887A (en) | 1979-12-10 | 1984-04-24 | Sloan-Kettering Institute | Process for making human antibody producing B-lymphocytes |
US4716111A (en) | 1982-08-11 | 1987-12-29 | Trustees Of Boston University | Process for producing human antibodies |
GB8607679D0 (en) | 1986-03-27 | 1986-04-30 | Winter G P | Recombinant dna product |
US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
GB8928874D0 (en) | 1989-12-21 | 1990-02-28 | Celltech Ltd | Humanised antibodies |
DK0710719T3 (da) | 1990-01-12 | 2007-07-09 | Amgen Fremont Inc | Frembringelse af xenogene antistoffer |
US5814318A (en) | 1990-08-29 | 1998-09-29 | Genpharm International Inc. | Transgenic non-human animals for producing heterologous antibodies |
US5545806A (en) | 1990-08-29 | 1996-08-13 | Genpharm International, Inc. | Ransgenic non-human animals for producing heterologous antibodies |
EP0519596B1 (en) | 1991-05-17 | 2005-02-23 | Merck & Co. Inc. | A method for reducing the immunogenicity of antibody variable domains |
CA2103059C (en) | 1991-06-14 | 2005-03-22 | Paul J. Carter | Method for making humanized antibodies |
US5565332A (en) | 1991-09-23 | 1996-10-15 | Medical Research Council | Production of chimeric antibodies - a combinatorial approach |
US5639641A (en) | 1992-09-09 | 1997-06-17 | Immunogen Inc. | Resurfacing of rodent antibodies |
ATE390933T1 (de) | 1995-04-27 | 2008-04-15 | Amgen Fremont Inc | Aus immunisierten xenomäusen stammende menschliche antikörper gegen il-8 |
EP0823941A4 (en) | 1995-04-28 | 2001-09-19 | Abgenix Inc | HUMAN ANTIBODIES DERIVED FROM IMMUNIZED XENO MOUSES |
US5916771A (en) | 1996-10-11 | 1999-06-29 | Abgenix, Inc. | Production of a multimeric protein by cell fusion method |
EP0942968B1 (en) | 1996-12-03 | 2008-02-27 | Amgen Fremont Inc. | Fully human antibodies that bind EGFR |
PL193780B1 (pl) | 1997-04-14 | 2007-03-30 | Micromet Ag | Sposób wytwarzania receptora przeciw ludzkim antygenom, ludzkie przeciwciało i środek farmaceutyczny |
US6235883B1 (en) | 1997-05-05 | 2001-05-22 | Abgenix, Inc. | Human monoclonal antibodies to epidermal growth factor receptor |
US7223397B1 (en) | 1999-01-07 | 2007-05-29 | Research Development Foundation | Potentiation of anti-CD38-Immunotoxin cytotoxicity |
GB0221574D0 (en) | 2002-09-17 | 2002-10-23 | Isis Innovation | Treatments |
NZ548990A (en) | 2004-02-06 | 2009-06-26 | Morphosys Ag | Anti-CD38 human antibodies and uses therefor |
TR201910145T4 (tr) | 2006-09-26 | 2019-08-21 | Genmab As | Tümörlerin tedavi edilmesine yönelik anti-CD38 artı kortikosteroidler artı bir kortikosteroid-olmayan kemoterapötik. |
US20080092384A1 (en) * | 2006-10-16 | 2008-04-24 | Schaake Mark D | Installation of Middle Bearing for a Crankshaft |
EP2191843A1 (en) | 2008-11-28 | 2010-06-02 | Sanofi-Aventis | Antitumor combinations containing antibodies recognizing specifically CD38 and cyclophosphamide |
EP2191841A1 (en) | 2008-11-28 | 2010-06-02 | Sanofi-Aventis | Antitumor combinations containing antibodies recognizing specifically CD38 and vincristine |
EP2191840A1 (en) | 2008-11-28 | 2010-06-02 | Sanofi-Aventis | Antitumor combinations containing antibodies recognizing specifically CD38 and melphalan |
-
2008
- 2008-11-28 EP EP08291116A patent/EP2191840A1/en not_active Ceased
-
2009
- 2009-11-25 TW TW098140158A patent/TWI454260B/zh active
- 2009-11-25 AR ARP090104545A patent/AR074219A1/es not_active Application Discontinuation
- 2009-11-25 PA PA20098850101A patent/PA8850101A1/es unknown
- 2009-11-25 UY UY0001032263A patent/UY32263A/es not_active Application Discontinuation
- 2009-11-27 CN CN200980148094.4A patent/CN102264385B/zh active Active
- 2009-11-27 MX MX2011005670A patent/MX342625B/es active IP Right Grant
- 2009-11-27 JP JP2011538092A patent/JP2012510461A/ja not_active Withdrawn
- 2009-11-27 KR KR1020117014746A patent/KR101733252B1/ko active IP Right Grant
- 2009-11-27 BR BRPI0921864-5A patent/BRPI0921864B1/pt active IP Right Grant
- 2009-11-27 US US13/130,862 patent/US9259406B2/en active Active
- 2009-11-27 SG SG2011037967A patent/SG171820A1/en unknown
- 2009-11-27 MY MYPI2011002367A patent/MY164577A/en unknown
- 2009-11-27 CA CA2744990A patent/CA2744990C/en not_active Expired - Fee Related
- 2009-11-27 UA UAA201108006A patent/UA107069C2/uk unknown
- 2009-11-27 ME MEP-2011-93A patent/ME01136B/me unknown
- 2009-11-27 EA EA201100864A patent/EA026867B1/ru not_active IP Right Cessation
- 2009-11-27 EP EP09775302A patent/EP2370094A1/en not_active Withdrawn
- 2009-11-27 WO PCT/IB2009/055389 patent/WO2010061357A1/en active Application Filing
- 2009-11-27 PE PE2011001107A patent/PE20120340A1/es active IP Right Grant
- 2009-11-27 NZ NZ593027A patent/NZ593027A/xx unknown
- 2009-11-27 AU AU2009321249A patent/AU2009321249B2/en active Active
-
2011
- 2011-05-11 TN TN2011000232A patent/TN2011000232A1/fr unknown
- 2011-05-19 EC EC2011011062A patent/ECSP11011062A/es unknown
- 2011-05-24 IL IL213116A patent/IL213116B/en active IP Right Grant
- 2011-05-26 CR CR20110280A patent/CR20110280A/es unknown
- 2011-05-27 NI NI201100105A patent/NI201100105A/es unknown
- 2011-05-27 HN HN2011001417A patent/HN2011001417A/es unknown
- 2011-05-27 ZA ZA2011/03925A patent/ZA201103925B/en unknown
- 2011-05-27 CL CL2011001254A patent/CL2011001254A1/es unknown
- 2011-05-27 CO CO11065644A patent/CO6440557A2/es unknown
- 2011-05-27 SV SV2011003924A patent/SV2011003924A/es unknown
- 2011-06-13 MA MA33937A patent/MA32896B1/fr unknown
-
2012
- 2012-05-25 HK HK12105154.7A patent/HK1164165A1/xx unknown
-
2015
- 2015-05-27 JP JP2015107404A patent/JP6148696B2/ja active Active
-
2017
- 2017-03-01 JP JP2017037860A patent/JP2017141233A/ja active Pending
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2003524587A (ja) * | 1998-06-05 | 2003-08-19 | マヨ ファウンデーション フォー メディカル エデュケーション アンド リサーチ | 多発性骨髄腫を処置するための、cd38に対する、遺伝子操作した抗体の使用 |
JP2008533977A (ja) * | 2005-03-23 | 2008-08-28 | ゲンマブ エー/エス | 多発性骨髄腫の治療のためのcd38に対する抗体 |
WO2008047242A2 (en) * | 2006-10-19 | 2008-04-24 | Sanofi-Aventis | Novel anti-cd38 antibodies for the treatment of cancer |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2015530399A (ja) * | 2012-09-25 | 2015-10-15 | モルフォシス エージー | 組み合わせ及びその使用 |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6148696B2 (ja) | Cd38を特異的に認識する抗体およびメルファランを含有する抗腫瘍性組合せ剤 | |
JP6215429B2 (ja) | Cd38を特異的に認識する抗体とシクロホスファミドとを含有する抗腫瘍組合せ | |
JP6072854B2 (ja) | Cd38を特異的に認識する抗体とシタラビンを含有する抗腫瘍性組合せ剤 | |
JP6130871B2 (ja) | Cd38を特異的に認識する抗体とビンクリスチンとを含有する抗腫瘍組合せ | |
TWI596116B (zh) | 包含專一性辨識cd38之抗體及硼替佐米(bortezomib)之抗腫瘤組合 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20121003 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20121003 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20131224 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20140317 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20140325 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20140623 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20150127 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20150527 |
|
A761 | Written withdrawal of application |
Free format text: JAPANESE INTERMEDIATE CODE: A761 Effective date: 20150618 |