CA3197506A1 - Fusion proteins comprising sulfoglucosamine sulfohydrolase enzymes and methods thereof - Google Patents
Fusion proteins comprising sulfoglucosamine sulfohydrolase enzymes and methods thereofInfo
- Publication number
- CA3197506A1 CA3197506A1 CA3197506A CA3197506A CA3197506A1 CA 3197506 A1 CA3197506 A1 CA 3197506A1 CA 3197506 A CA3197506 A CA 3197506A CA 3197506 A CA3197506 A CA 3197506A CA 3197506 A1 CA3197506 A1 CA 3197506A1
- Authority
- CA
- Canada
- Prior art keywords
- polypeptide
- sgsh
- amino acid
- acid sequence
- protein
- 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.)
- Pending
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2881—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against CD71
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/62—DNA sequences coding for fusion proteins
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y310/00—Hydrolases acting on sulfur-nitrogen bonds (3.10)
- C12Y310/01—Hydrolases acting on sulfur-nitrogen bonds (3.10) acting on sulfur-nitrogen bonds (3.10.1)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y310/00—Hydrolases acting on sulfur-nitrogen bonds (3.10)
- C12Y310/01—Hydrolases acting on sulfur-nitrogen bonds (3.10) acting on sulfur-nitrogen bonds (3.10.1)
- C12Y310/01001—N-Sulfoglucosamine sulfohydrolase (3.10.1.1)
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/40—Immunoglobulins specific features characterized by post-translational modification
- C07K2317/41—Glycosylation, sialylation, or fucosylation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/52—Constant or Fc region; Isotype
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Genetics & Genomics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- Immunology (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Epidemiology (AREA)
- Biophysics (AREA)
- Gastroenterology & Hepatology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Diabetes (AREA)
- Physics & Mathematics (AREA)
- Plant Pathology (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Enzymes And Modification Thereof (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US202063091800P | 2020-10-14 | 2020-10-14 | |
| US63/091,800 | 2020-10-14 | ||
| PCT/US2021/054860 WO2022081765A1 (en) | 2020-10-14 | 2021-10-13 | Fusion proteins comprising sulfoglucosamine sulfohydrolase enzymes and methods thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA3197506A1 true CA3197506A1 (en) | 2022-04-21 |
Family
ID=78725609
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA3197506A Pending CA3197506A1 (en) | 2020-10-14 | 2021-10-13 | Fusion proteins comprising sulfoglucosamine sulfohydrolase enzymes and methods thereof |
Country Status (18)
| Country | Link |
|---|---|
| US (2) | US11884944B2 (https=) |
| EP (1) | EP4229192A1 (https=) |
| JP (1) | JP2023545707A (https=) |
| KR (1) | KR20230086703A (https=) |
| CN (1) | CN116916947A (https=) |
| AR (1) | AR123788A1 (https=) |
| AU (1) | AU2021362209B2 (https=) |
| CA (1) | CA3197506A1 (https=) |
| CL (1) | CL2023001034A1 (https=) |
| CO (1) | CO2023005260A2 (https=) |
| CR (1) | CR20230178A (https=) |
| EC (1) | ECSP23035251A (https=) |
| IL (1) | IL302029A (https=) |
| MA (1) | MA71661A (https=) |
| MX (1) | MX2023004335A (https=) |
| PE (1) | PE20231931A1 (https=) |
| TW (1) | TW202229547A (https=) |
| WO (1) | WO2022081765A1 (https=) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110506055A (zh) | 2017-02-17 | 2019-11-26 | 戴纳立制药公司 | 工程改造的转铁蛋白受体结合多肽 |
| CR20200129A (es) | 2017-10-02 | 2020-08-22 | Denali Therapeutics Inc | Proteínas de fusión que comprenden enzimas de terapia de reemplazo de enzimas |
| BR112021015656A2 (pt) | 2019-02-20 | 2021-10-05 | Denali Therapeutics Inc. | Anticorpos anti-trem2 e métodos de uso dos mesmos |
| PH12022551598A1 (en) | 2019-12-23 | 2023-11-20 | Denali Therapeutics Inc | Progranulin variants |
| TW202542190A (zh) | 2023-12-20 | 2025-11-01 | 美商戴納立製藥公司 | 包含酸性α—葡萄糖苷酶之融合蛋白及其方法 |
Family Cites Families (52)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5863782A (en) | 1995-04-19 | 1999-01-26 | Women's And Children's Hospital | Synthetic mammalian sulphamidase and genetic sequences encoding same |
| US6194551B1 (en) | 1998-04-02 | 2001-02-27 | Genentech, Inc. | Polypeptide variants |
| WO2003057179A2 (en) | 2002-01-11 | 2003-07-17 | Biomarin Pharmaceutical, Inc. | Use of p97 as an enzyme delivery system for the delivery of therapeutic lysosomal enzymes |
| US20050142141A1 (en) | 2002-11-27 | 2005-06-30 | Pardridge William M. | Delivery of enzymes to the brain |
| AU2003286870A1 (en) | 2003-06-05 | 2005-01-04 | Salk Institute For Biological Studies | Targeting polypeptides to the central nervous system |
| CA2711590C (en) | 2008-01-18 | 2021-03-23 | Biomarin Pharmaceutical Inc. | Manufacture of active highly phosphorylated human lysosomal sulfatase enzymes and uses thereof |
| EP2394667A1 (en) | 2010-06-10 | 2011-12-14 | Laboratorios Del Dr. Esteve, S.A. | Vectors and sequences for the treatment of diseases |
| PT3103469T (pt) | 2010-06-25 | 2021-03-04 | Shire Human Genetic Therapies | Administração de agentes terapêuticos no snc |
| JP6073783B2 (ja) | 2010-06-25 | 2017-02-01 | シャイアー ヒューマン ジェネティック セラピーズ インコーポレイテッド | ヘパランｎ−スルファターゼのｃｎｓ送達のための方法および組成物 |
| ES2692268T5 (en) | 2011-03-29 | 2025-02-26 | Roche Glycart Ag | Antibody fc variants |
| AU2012294673B2 (en) | 2011-08-05 | 2015-11-26 | Bioasis Technologies Inc. | p97 fragments with transfer activity |
| CA3140358A1 (en) | 2012-07-31 | 2014-02-06 | Bioasis Technologies, Inc. | Dephosphorylated lysosomal storage disease proteins and methods of use thereof |
| HUE045144T2 (hu) | 2012-08-29 | 2019-12-30 | Hoffmann La Roche | Véragygát-shuttle |
| AU2014243816B2 (en) | 2013-03-13 | 2019-01-31 | Bioasis Technologies Inc. | Fragments of p97 and uses thereof |
| EP2970940B1 (en) | 2013-03-14 | 2018-07-25 | Translate Bio, Inc. | Mrna therapeutic compositions and use to treat diseases and disorders |
| JP6692293B2 (ja) | 2013-07-22 | 2020-05-13 | アーマジェン・インコーポレイテッドＡｒｍａｇｅｎ， Ｉｎｃ． | Ｃｎｓにおける酵素活性を増大するための方法および組成物 |
| SI2970413T1 (sl) | 2014-04-01 | 2018-10-30 | Swedish Orphan Biovitrum Ab (Publ) | Modificirana sulfamidaza in proizvodja le-te |
| DK3215528T3 (da) | 2014-11-06 | 2019-10-07 | Hoffmann La Roche | Fc-regionvarianter med modificeret FcRn-binding og anvendelsesfremgangsmåder |
| WO2016081640A1 (en) | 2014-11-19 | 2016-05-26 | Genentech, Inc. | Anti-transferrin receptor / anti-bace1 multispecific antibodies and methods of use |
| EA039366B1 (ru) | 2015-06-24 | 2022-01-19 | Джей Си Ар ФАРМАСЬЮТИКАЛЗ КО., ЛТД. | Антитело к рецептору трансферрина человека, проникающее через гематоэнцефалический барьер |
| HUE057952T2 (hu) | 2015-06-24 | 2022-06-28 | Hoffmann La Roche | Anti-transzferrin receptor antitestek testreszabott affinitással |
| DK3386534T3 (da) | 2015-12-08 | 2020-11-30 | Regeneron Pharma | Sammensætninger og fremgangsmåder til internalisering af enzymer |
| AR107483A1 (es) | 2016-01-29 | 2018-05-02 | Hanmi Pharm Ind Co Ltd | Conjugado de enzimas terapéuticas |
| MX2018010196A (es) | 2016-02-24 | 2018-11-19 | Biomarin Pharm Inc | Proteinas de fusion de enzimas lisosomales terapeuticas dirigidas, formulaciones asociadas y usos de las mismas. |
| EP3494216B1 (en) | 2016-08-06 | 2025-10-15 | Ossianix, Inc. | In vivo methods for selecting peptides that cross the blood brain barrier, related compositions and methods of use |
| SG11201901495YA (en) | 2016-08-25 | 2019-03-28 | Jcr Pharmaceuticals Co Ltd | Method for producing antibody fusion protein |
| US20190352335A1 (en) | 2016-12-19 | 2019-11-21 | Hanmi Pharm. Co., Ltd. | Brain targeting long-acting protein conjugate |
| KR102497564B1 (ko) | 2016-12-26 | 2023-02-07 | 제이씨알 파마 가부시키가이샤 | 혈액뇌관문을 통과하는 신규한 항인간 트랜스페린 수용체 항체 |
| AU2017386888B2 (en) | 2016-12-28 | 2024-08-08 | Jcr Pharmaceuticals Co., Ltd. | Lyophilized preparation |
| WO2018152285A1 (en) | 2017-02-17 | 2018-08-23 | Denali Therapeutics Inc. | Transferrin receptor transgenic models |
| CN110506055A (zh) | 2017-02-17 | 2019-11-26 | 戴纳立制药公司 | 工程改造的转铁蛋白受体结合多肽 |
| SG11201907422RA (en) | 2017-02-17 | 2019-09-27 | Denali Therapeutics Inc | Anti-tau antibodies and methods of use thereof |
| GB201702863D0 (en) | 2017-02-22 | 2017-04-05 | Evox Therapeutics Ltd | Improved loading of EVs with therapeutic proteins |
| AU2018295994B2 (en) | 2017-07-07 | 2025-02-06 | Hanmi Pharm. Co., Ltd. | Novel therapeutic enzyme fusion protein and use thereof |
| EP3665194A4 (en) | 2017-08-10 | 2021-07-07 | Denali Therapeutics Inc. | AFFINITY BASED METHODS OF USING TRANSFERRIN RECEPTOR BINDING PROTEINS |
| CR20200129A (es) | 2017-10-02 | 2020-08-22 | Denali Therapeutics Inc | Proteínas de fusión que comprenden enzimas de terapia de reemplazo de enzimas |
| WO2019094608A1 (en) | 2017-11-08 | 2019-05-16 | Denali Therapeutics Inc. | Anti-bace1 antibodies and methods of use thereof |
| CN111511910B (zh) | 2017-12-22 | 2024-11-08 | 韩美药品株式会社 | 具有新颖结构的治疗酶融合蛋白及其用途 |
| TW201934573A (zh) | 2018-01-10 | 2019-09-01 | 美商戴納立製藥公司 | 轉鐵蛋白受體結合性多肽及其用途 |
| WO2019145500A1 (en) | 2018-01-26 | 2019-08-01 | Swedish Orphan Biovitrum Ab (Publ) | Method of treatment |
| JP7337099B2 (ja) * | 2018-05-25 | 2023-09-01 | アレクトル エルエルシー | 抗ｓｉｒｐａ抗体およびその使用法 |
| WO2019246071A1 (en) | 2018-06-18 | 2019-12-26 | Denali Therapeutics Inc. | Fusion proteins comprising progranulin |
| WO2020037150A2 (en) | 2018-08-16 | 2020-02-20 | Denali Therapeutics Inc. | Engineered bispecific proteins |
| JP2021534220A (ja) | 2018-08-22 | 2021-12-09 | デナリ セラピューティクス インコーポレイテッドDenali Therapeutics Inc. | 抗ｈｅｒ２ポリペプチド及びそれらの使用の方法 |
| CR20210155A (es) * | 2018-08-31 | 2021-05-10 | Alector Llc | Anticuerpos anti-cd33 y métodos para usarlos |
| CA3134538A1 (en) | 2019-04-03 | 2020-10-08 | Denali Therapeutics Inc. | Formulations of protein molecules comprising iduronate 2-sulfatase |
| WO2021133907A1 (en) | 2019-12-23 | 2021-07-01 | Denali Therapeutics Inc. | Progranulin variants |
| PH12022551598A1 (en) | 2019-12-23 | 2023-11-20 | Denali Therapeutics Inc | Progranulin variants |
| WO2021146256A1 (en) | 2020-01-13 | 2021-07-22 | Denali Therapeutics Inc. | Anti-trem2 antibodies and methods of use thereof |
| JP2023512450A (ja) | 2020-01-13 | 2023-03-27 | デナリ セラピューティクス インコーポレイテッド | 抗ｔｒｅｍ２抗体及びその使用方法 |
| WO2021158986A1 (en) | 2020-02-07 | 2021-08-12 | Denali Therapeutics Inc. | Methods for the treatment of hunter syndrome |
| AU2021224200A1 (en) | 2020-02-19 | 2022-09-08 | Denali Therapeutics Inc. | Engineered anti-HER2 bispecific proteins |
-
2021
- 2021-10-13 EP EP21811560.8A patent/EP4229192A1/en active Pending
- 2021-10-13 PE PE2023001396A patent/PE20231931A1/es unknown
- 2021-10-13 CR CR20230178A patent/CR20230178A/es unknown
- 2021-10-13 WO PCT/US2021/054860 patent/WO2022081765A1/en not_active Ceased
- 2021-10-13 AU AU2021362209A patent/AU2021362209B2/en active Active
- 2021-10-13 MA MA71661A patent/MA71661A/fr unknown
- 2021-10-13 MX MX2023004335A patent/MX2023004335A/es unknown
- 2021-10-13 IL IL302029A patent/IL302029A/en unknown
- 2021-10-13 CA CA3197506A patent/CA3197506A1/en active Pending
- 2021-10-13 KR KR1020237014440A patent/KR20230086703A/ko active Pending
- 2021-10-13 JP JP2023521078A patent/JP2023545707A/ja active Pending
- 2021-10-13 CN CN202180069692.3A patent/CN116916947A/zh active Pending
- 2021-10-14 TW TW110138229A patent/TW202229547A/zh unknown
- 2021-10-14 AR ARP210102838A patent/AR123788A1/es unknown
-
2022
- 2022-06-30 US US17/855,543 patent/US11884944B2/en active Active
-
2023
- 2023-04-11 CL CL2023001034A patent/CL2023001034A1/es unknown
- 2023-04-25 CO CONC2023/0005260A patent/CO2023005260A2/es unknown
- 2023-05-12 EC ECSENADI202335251A patent/ECSP23035251A/es unknown
-
2024
- 2024-01-12 US US18/411,592 patent/US20240150736A1/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| IL302029A (en) | 2023-06-01 |
| MX2023004335A (es) | 2023-05-04 |
| MA71661A (fr) | 2025-05-30 |
| TW202229547A (zh) | 2022-08-01 |
| AU2021362209B2 (en) | 2026-02-12 |
| CN116916947A (zh) | 2023-10-20 |
| US11884944B2 (en) | 2024-01-30 |
| JP2023545707A (ja) | 2023-10-31 |
| CR20230178A (es) | 2023-07-26 |
| WO2022081765A1 (en) | 2022-04-21 |
| US20240150736A1 (en) | 2024-05-09 |
| AU2021362209A1 (en) | 2023-05-18 |
| US20230062800A1 (en) | 2023-03-02 |
| EP4229192A1 (en) | 2023-08-23 |
| AR123788A1 (es) | 2023-01-11 |
| KR20230086703A (ko) | 2023-06-15 |
| ECSP23035251A (es) | 2023-10-31 |
| CL2023001034A1 (es) | 2023-10-06 |
| CO2023005260A2 (es) | 2023-05-19 |
| PE20231931A1 (es) | 2023-12-01 |
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Free format text: FEE DESCRIPTION TEXT: MF (APPLICATION, 3RD ANNIV.) - STANDARD Year of fee payment: 3 |
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