CN1891716B - 一种无丝裂原活性抗cd3小分子抗体的设计方法 - Google Patents
一种无丝裂原活性抗cd3小分子抗体的设计方法 Download PDFInfo
- Publication number
- CN1891716B CN1891716B CN2005100829453A CN200510082945A CN1891716B CN 1891716 B CN1891716 B CN 1891716B CN 2005100829453 A CN2005100829453 A CN 2005100829453A CN 200510082945 A CN200510082945 A CN 200510082945A CN 1891716 B CN1891716 B CN 1891716B
- Authority
- CN
- China
- Prior art keywords
- antibody
- mini
- ycd3
- antibodies
- gene
- 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.)
- Expired - Fee Related
Links
- 230000000694 effects Effects 0.000 title claims abstract description 32
- 239000003226 mitogen Substances 0.000 title claims abstract description 24
- 238000000034 method Methods 0.000 title description 24
- 208000023275 Autoimmune disease Diseases 0.000 claims abstract description 3
- 230000001154 acute effect Effects 0.000 claims abstract description 3
- 239000003814 drug Substances 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 230000001404 mediated effect Effects 0.000 claims description 2
- 125000003275 alpha amino acid group Chemical group 0.000 claims 4
- 102000009109 Fc receptors Human genes 0.000 abstract description 8
- 108010087819 Fc receptors Proteins 0.000 abstract description 8
- 230000027455 binding Effects 0.000 abstract description 7
- 238000002054 transplantation Methods 0.000 abstract description 6
- 230000001506 immunosuppresive effect Effects 0.000 abstract description 3
- 210000000056 organ Anatomy 0.000 abstract description 3
- 230000000890 antigenic effect Effects 0.000 abstract description 2
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 abstract 1
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 abstract 1
- 238000012407 engineering method Methods 0.000 abstract 1
- 230000002265 prevention Effects 0.000 abstract 1
- 230000001737 promoting effect Effects 0.000 abstract 1
- 210000000278 spinal cord Anatomy 0.000 abstract 1
- 108090000623 proteins and genes Proteins 0.000 description 35
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 23
- 238000003752 polymerase chain reaction Methods 0.000 description 21
- 108090000790 Enzymes Proteins 0.000 description 13
- 102000004190 Enzymes Human genes 0.000 description 13
- 239000012634 fragment Substances 0.000 description 13
- 230000008859 change Effects 0.000 description 12
- 108091008146 restriction endonucleases Proteins 0.000 description 12
- 238000013461 design Methods 0.000 description 11
- 102000017420 CD3 protein, epsilon/gamma/delta subunit Human genes 0.000 description 10
- 210000004027 cell Anatomy 0.000 description 10
- 238000002474 experimental method Methods 0.000 description 10
- 230000004936 stimulating effect Effects 0.000 description 10
- 238000012360 testing method Methods 0.000 description 10
- 239000000427 antigen Substances 0.000 description 9
- 102000036639 antigens Human genes 0.000 description 9
- 108091007433 antigens Proteins 0.000 description 9
- 239000013604 expression vector Substances 0.000 description 9
- 150000001413 amino acids Chemical class 0.000 description 8
- 238000003114 enzyme-linked immunosorbent spot assay Methods 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 108090000695 Cytokines Proteins 0.000 description 7
- 102000004127 Cytokines Human genes 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 7
- 238000010367 cloning Methods 0.000 description 7
- 238000001962 electrophoresis Methods 0.000 description 7
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 7
- 230000006870 function Effects 0.000 description 7
- 229920000936 Agarose Polymers 0.000 description 6
- 108010076504 Protein Sorting Signals Proteins 0.000 description 5
- 238000000137 annealing Methods 0.000 description 5
- 230000004087 circulation Effects 0.000 description 5
- 238000010276 construction Methods 0.000 description 5
- 238000011156 evaluation Methods 0.000 description 5
- 210000004698 lymphocyte Anatomy 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- 238000005457 optimization Methods 0.000 description 5
- 230000000638 stimulation Effects 0.000 description 5
- 231100000331 toxic Toxicity 0.000 description 5
- 230000002588 toxic effect Effects 0.000 description 5
- 102100037850 Interferon gamma Human genes 0.000 description 4
- 108010074328 Interferon-gamma Proteins 0.000 description 4
- 239000012980 RPMI-1640 medium Substances 0.000 description 4
- 229940024606 amino acid Drugs 0.000 description 4
- 235000001014 amino acid Nutrition 0.000 description 4
- 230000003321 amplification Effects 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 230000008034 disappearance Effects 0.000 description 4
- 230000008629 immune suppression Effects 0.000 description 4
- 238000003199 nucleic acid amplification method Methods 0.000 description 4
- 239000002773 nucleotide Substances 0.000 description 4
- 125000003729 nucleotide group Chemical group 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 102000004196 processed proteins & peptides Human genes 0.000 description 4
- 108090000765 processed proteins & peptides Proteins 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 101100230376 Acetivibrio thermocellus (strain ATCC 27405 / DSM 1237 / JCM 9322 / NBRC 103400 / NCIMB 10682 / NRRL B-4536 / VPI 7372) celI gene Proteins 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 3
- 241000699802 Cricetulus griseus Species 0.000 description 3
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 3
- 108010002350 Interleukin-2 Proteins 0.000 description 3
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 3
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 3
- 239000002131 composite material Substances 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 230000035772 mutation Effects 0.000 description 3
- 210000001672 ovary Anatomy 0.000 description 3
- 238000001262 western blot Methods 0.000 description 3
- ARPVSMCNIDAQBO-YUMQZZPRSA-N Gln-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H](N)CCC(N)=O ARPVSMCNIDAQBO-YUMQZZPRSA-N 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 210000001744 T-lymphocyte Anatomy 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 238000005094 computer simulation Methods 0.000 description 2
- 239000008367 deionised water Substances 0.000 description 2
- 229910021641 deionized water Inorganic materials 0.000 description 2
- UQLDLKMNUJERMK-UHFFFAOYSA-L di(octadecanoyloxy)lead Chemical compound [Pb+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O UQLDLKMNUJERMK-UHFFFAOYSA-L 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 230000013595 glycosylation Effects 0.000 description 2
- 238000006206 glycosylation reaction Methods 0.000 description 2
- 230000005847 immunogenicity Effects 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 238000003032 molecular docking Methods 0.000 description 2
- 239000000178 monomer Substances 0.000 description 2
- 210000005087 mononuclear cell Anatomy 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 210000005259 peripheral blood Anatomy 0.000 description 2
- 239000011886 peripheral blood Substances 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- NFGXHKASABOEEW-UHFFFAOYSA-N 1-methylethyl 11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate Chemical compound COC(C)(C)CCCC(C)CC=CC(C)=CC(=O)OC(C)C NFGXHKASABOEEW-UHFFFAOYSA-N 0.000 description 1
- -1 37 °C 1 hour Chemical compound 0.000 description 1
- 244000201986 Cassia tora Species 0.000 description 1
- 235000014552 Cassia tora Nutrition 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 208000000059 Dyspnea Diseases 0.000 description 1
- 206010013975 Dyspnoeas Diseases 0.000 description 1
- 240000004859 Gamochaeta purpurea Species 0.000 description 1
- 101000878602 Homo sapiens Immunoglobulin alpha Fc receptor Proteins 0.000 description 1
- 101000611183 Homo sapiens Tumor necrosis factor Proteins 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- 108010091135 Immunoglobulin Fc Fragments Proteins 0.000 description 1
- 102100038005 Immunoglobulin alpha Fc receptor Human genes 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- DEFJQIDDEAULHB-IMJSIDKUSA-N L-alanyl-L-alanine Chemical compound C[C@H](N)C(=O)N[C@@H](C)C(O)=O DEFJQIDDEAULHB-IMJSIDKUSA-N 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- 238000012408 PCR amplification Methods 0.000 description 1
- 208000003251 Pruritus Diseases 0.000 description 1
- 206010052779 Transplant rejections Diseases 0.000 description 1
- 206010044565 Tremor Diseases 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 108010056243 alanylalanine Proteins 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 239000013599 cloning vector Substances 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- 206010052015 cytokine release syndrome Diseases 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- ZFGMDIBRIDKWMY-PASTXAENSA-N heparin Chemical compound CC(O)=N[C@@H]1[C@@H](O)[C@H](O)[C@@H](COS(O)(=O)=O)O[C@@H]1O[C@@H]1[C@@H](C(O)=O)O[C@@H](O[C@H]2[C@@H]([C@@H](OS(O)(=O)=O)[C@@H](O[C@@H]3[C@@H](OC(O)[C@H](OS(O)(=O)=O)[C@H]3O)C(O)=O)O[C@@H]2O)CS(O)(=O)=O)[C@H](O)[C@H]1O ZFGMDIBRIDKWMY-PASTXAENSA-N 0.000 description 1
- 229960001008 heparin sodium Drugs 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 229940126619 mouse monoclonal antibody Drugs 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 208000005333 pulmonary edema Diseases 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000000452 restraining effect Effects 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000002864 sequence alignment Methods 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 235000020183 skimmed milk Nutrition 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000003153 stable transfection Methods 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000008280 toxic mechanism Effects 0.000 description 1
- 238000010023 transfer printing Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
Images
Landscapes
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
Description
Claims (4)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN2005100829453A CN1891716B (zh) | 2005-07-08 | 2005-07-08 | 一种无丝裂原活性抗cd3小分子抗体的设计方法 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN2005100829453A CN1891716B (zh) | 2005-07-08 | 2005-07-08 | 一种无丝裂原活性抗cd3小分子抗体的设计方法 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN1891716A CN1891716A (zh) | 2007-01-10 |
CN1891716B true CN1891716B (zh) | 2012-11-21 |
Family
ID=37596938
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN2005100829453A Expired - Fee Related CN1891716B (zh) | 2005-07-08 | 2005-07-08 | 一种无丝裂原活性抗cd3小分子抗体的设计方法 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN1891716B (zh) |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP3112382A1 (en) * | 2009-12-29 | 2017-01-04 | Emergent Product Development Seattle, LLC | Heterodimer binding proteins and uses thereof |
CN102727888B (zh) * | 2011-03-31 | 2014-06-11 | 熊慧 | 一种抗人t淋巴细胞cd3表面抗原单克隆抗体在制备治疗糖尿病肾病药物中的应用 |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1122317A1 (en) * | 1998-10-13 | 2001-08-08 | Ono Pharmaceutical Co., Ltd. | Antibody against glycerylaldehyde-3-phosphate dehydrogenase and utilization thereof |
CN1583753A (zh) * | 2004-05-26 | 2005-02-23 | 中国药科大学 | 具有释放NO功能的噁二唑并[3,4-d]嘧啶苷类化合物及其药学上的用途 |
-
2005
- 2005-07-08 CN CN2005100829453A patent/CN1891716B/zh not_active Expired - Fee Related
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1122317A1 (en) * | 1998-10-13 | 2001-08-08 | Ono Pharmaceutical Co., Ltd. | Antibody against glycerylaldehyde-3-phosphate dehydrogenase and utilization thereof |
CN1583753A (zh) * | 2004-05-26 | 2005-02-23 | 中国药科大学 | 具有释放NO功能的噁二唑并[3,4-d]嘧啶苷类化合物及其药学上的用途 |
Non-Patent Citations (1)
Title |
---|
郑军华!200003上海等.鼠抗人CD3、CD4单克隆抗体治疗肾移植后急性排斥反应的疗效观察.《中华器官移植杂志》.2000,第21卷(第01期), * |
Also Published As
Publication number | Publication date |
---|---|
CN1891716A (zh) | 2007-01-10 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP7273453B2 (ja) | IL-15/IL-15RアルファFc融合タンパク質およびPD-1抗体の断片を含む二重特異性ヘテロ二量体融合タンパク質 | |
EP3882276A1 (en) | Bispecific antibody, preparation method therefor and application thereof | |
TW201900674A (zh) | 含有TGF-β受體的融合蛋白及其醫藥用途 | |
JP2020529832A (ja) | IL−15/IL−15Rαおよび抗原結合ドメインを含む標的化ヘテロダイマーFc融合タンパク質 | |
KR20210010862A (ko) | IL-15/IL-15Rα Fc-융합 단백질 및 PD-1 항원 결합 도메인을 함유하는 PD-1 표적화 이종이량체 융합 단백질 및 이의 용도 | |
CN109476747A (zh) | 结合免疫调节性蛋白和肿瘤抗原的双特异性结合蛋白 | |
CN107969128A (zh) | 具有可调的亲和力的免疫调节蛋白 | |
CN106414497A (zh) | 三特异性结合分子和其使用方法 | |
BR112021006783A2 (pt) | proteína de fusão fc heterodimérica de il-15/r¿ direcionada, composição de ácido nucleico, composição de vetor de expressão, célula hospedeira, e, métodos de produção da proteína de fusão fc heterodimérica de il-15/r¿ direcionada e de tratamento de um câncer. | |
CN104093841A (zh) | 基于IL-15和IL-15Rα SUSHI结构域的免疫细胞因子 | |
JP2022521937A (ja) | NKp30に結合する抗体分子およびその使用 | |
CN104788567A (zh) | 一种靶向鼠T淋巴细胞CD3和人肿瘤抗原EpCAM的双特异性抗体制备方法及应用 | |
KR20210107747A (ko) | 항체 융합 단백질, 이의 제조 방법 및 이의 적용 | |
IL301027A (en) | Mutant AI 2 and its application | |
CN114945596A (zh) | 用于调节免疫细胞衔接效应的手段和方法 | |
EP4303231A1 (en) | Bispecific antibody | |
JP2019529368A (ja) | 共刺激受容体およびチェックポイント受容体に連結する二重特異性免疫調節抗体 | |
JP2023554119A (ja) | 安定化されたtcrコンストラクト及び使用方法 | |
TW202229353A (zh) | 抗tspan8-抗cd3雙特異性抗體及抗tspan8抗體 | |
CN1891716B (zh) | 一种无丝裂原活性抗cd3小分子抗体的设计方法 | |
WO2020135804A1 (zh) | 异源二聚体融合蛋白 | |
JP2022522815A (ja) | Tsg-6抗体およびその用途 | |
US20230265185A1 (en) | Anti-cd22 single domain antibodies and therapeutic constructs | |
KR20240019786A (ko) | Cd20, nkp46, cd16에 결합하고 il-2에 접합된 다중특이적 항체 | |
WO2021145946A1 (en) | Multispecific treg binding molecules |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
DD01 | Delivery of document by public notice |
Addressee: Li Yan Document name: Notification of an Office Action |
|
C53 | Correction of patent of invention or patent application | ||
CB02 | Change of applicant information |
Address after: Branch of Beijing economic and Technological Development Zone of Beijing City fourteen street 101111 No. ninety-nine Building No. 3 102 Applicant after: BEIJING MABWORKS BIOTECH Co.,Ltd. Address before: 100176, Beijing economic and Technological Development Zone Hongda North Road No. 12, block B, zone 3, 2 floor Applicant before: BEIJING MABWORKS BIOTECH Co.,Ltd. |
|
C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
CP02 | Change in the address of a patent holder |
Address after: Branch of Beijing economic and Technological Development Zone fourteen 101111 street Beijing City Hospital No. 20, No. 16 Building 5 unit 3 Patentee after: BEIJING MABWORKS BIOTECH Co.,Ltd. Address before: Branch of Beijing economic and Technological Development Zone of Beijing City fourteen street 101111 No. ninety-nine Building No. 3 102 Patentee before: BEIJING MABWORKS BIOTECH Co.,Ltd. |
|
CP02 | Change in the address of a patent holder | ||
TR01 | Transfer of patent right |
Effective date of registration: 20211215 Address after: 100850 No. 27 Taiping Road, Beijing, Haidian District Patentee after: ACADEMY OF MILITARY MEDICAL SCIENCES Address before: 101111 3rd floor, unit 5, building 16, courtyard 20, Kechuang 14th Street, Beijing Economic and Technological Development Zone, Beijing Patentee before: BEIJING MABWORKS BIOTECH Co.,Ltd. |
|
TR01 | Transfer of patent right | ||
DD01 | Delivery of document by public notice |
Addressee: BEIJING MABWORKS BIOTECH Co.,Ltd. Person in charge of patentsThe principal of patent Document name: Notification of conformity |
|
DD01 | Delivery of document by public notice | ||
CF01 | Termination of patent right due to non-payment of annual fee | ||
CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20121121 |