US20020006400A1 - Recombinant human CLN2 protein and methods of its production and use - Google Patents

Recombinant human CLN2 protein and methods of its production and use Download PDF

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Publication number
US20020006400A1
US20020006400A1 US09/852,918 US85291801A US2002006400A1 US 20020006400 A1 US20020006400 A1 US 20020006400A1 US 85291801 A US85291801 A US 85291801A US 2002006400 A1 US2002006400 A1 US 2002006400A1
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US
United States
Prior art keywords
protein
cln2
cln2 protein
cells
lincl
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.)
Abandoned
Application number
US09/852,918
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English (en)
Inventor
Peter Lobel
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Rutgers Health
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Individual
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Filing date
Publication date
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Priority to US09/852,918 priority Critical patent/US20020006400A1/en
Priority to EP01937337A priority patent/EP1292326B1/de
Priority to JP2001581853A priority patent/JP4843774B2/ja
Priority to AT01937337T priority patent/ATE360438T1/de
Priority to DE60128084T priority patent/DE60128084T2/de
Priority to PCT/US2001/015386 priority patent/WO2001085200A2/en
Priority to MXPA02011162A priority patent/MXPA02011162A/es
Priority to CA2408380A priority patent/CA2408380C/en
Priority to AU2001263085A priority patent/AU2001263085A1/en
Priority to BR0110746-1A priority patent/BR0110746A/pt
Assigned to MEDICINE AND DENTISTRY OF NEW JERSEY, UNIVERSITY OF reassignment MEDICINE AND DENTISTRY OF NEW JERSEY, UNIVERSITY OF ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: LOBEL, PETER
Publication of US20020006400A1 publication Critical patent/US20020006400A1/en
Priority to US10/255,317 priority patent/US20030091554A1/en
Priority to US11/507,945 priority patent/US7811559B2/en
Assigned to NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT reassignment NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT EXECUTIVE ORDER 9424, CONFIRMATORY LICENSE Assignors: UNIVERSITY OF MED/DENT NJ NEWARK
Priority to US12/881,066 priority patent/US8029781B2/en
Priority to US13/220,572 priority patent/US8277800B2/en
Priority to US13/598,556 priority patent/US20130273018A1/en
Abandoned legal-status Critical Current

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    • 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)
    • A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
    • A61K38/4813—Exopeptidases (3.4.11. to 3.4.19)
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y304/00—Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
    • C12Y304/14—Dipeptidyl-peptidases and tripeptidyl-peptidases (3.4.14)
    • C12Y304/14009—Tripeptidyl-peptidase I (3.4.14.9)

Definitions

  • the CLN2 protein may be administered in a composition with pharmaceutically acceptable carriers and/or excipients.
  • pharmaceutically acceptable refers to molecular entities and compositions that are physiologically tolerable and do not typically produce an undesired reaction, such as gastric upset, dizziness, allergic reactions and the like, when administered.
  • pharmaceutically acceptable means approved by a regulatory agency of the Federal or a state government or listed in the U.S. Pharmacopeia or other generally recognized pharmacopeia for use in animals, and more particularly in humans, although a pharmaceutically acceptable carrier of the invention may share the attributes of such an approved carrier without itself having been approved.
  • an amount of CLN2 protein effective to reduce or eliminate the symptoms caused by the deficiency in CLN2 protein is readily determined by the skilled practitioner.
  • alleviation i.e. reduction or elimination
  • the measurement may be made on cell samples, for example brain neurons, by determining the amount of storage products present in lysosomes and comparing with normal control cells to confirm relief of the condition.
  • the dosage may be determined by a skilled practitioner depending on the age, size, and condition of the patient.
  • CLN2 protein or composition can be delivered in a controlled release system.
  • a controlled release system may be administered using intravenous infusion, an implantable osmotic pump, a transdermal patch, liposomes, or other modes of administration.
  • a pump may be used (see Langer, supra; Sefton, CRC Crit. Ref. Biomed. Eng. 14:201 (1987); Buchwald et al., Surgery 88:507 (1980); Saudek et al., N. Engl. J. Med. 321:574 (1989)).
  • polymeric materials can be used (see Medical Applications of Controlled Release, Langer and Wise (eds.), CRC Pres., Boca Raton, Fla.
  • the TPP-I activity in conditioned medium was assayed and the highest expressor was treated with MTX to select for clones that had undergone gene amplification.
  • the TPP-I activity level in conditioned medium was increased by 15 fold over endogenous level after transfection and G418 selection and further increased to >1000-fold over untransfected cells after MTX amplification (FIG. 1).
  • the cells were lysed by adding 1% Nonidet P40/10 mM Tris pH 7.5/150 mM NaCl (0.2 ml/well) and incubated for 1 hour at 4° C. on a rocking platform. The lysate was transferred to microfuge tubes and centrifuged for 20 min at 13,000 ⁇ g. The supernatant was used for enzyme activity and protein (Lowry, et al. (1951) J Biol Chem 193, 265-275) assays.
  • the TPP-I activity reflects either the mature CLN2 protein (triangles) or both precursor and mature CLN2 protein (circles) present within the neurons (FIG. 12 ).
  • concentrations of recombinant CLN2 protein where there was a significant increase of TPP-I activity over endogenous levels >3 nM in the absence of M6P and >10 nM in the presence of M6P
  • ⁇ 80% of the endocytosed CLN2 protein was in the mature form (FIG. 12). This indicates that the enzyme is targeted to an acidic intracellular compartment but that this process is slower or less efficient than in fibroblasts.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Organic Chemistry (AREA)
  • Epidemiology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Immunology (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Biochemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • Hospice & Palliative Care (AREA)
  • Psychiatry (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Enzymes And Modification Thereof (AREA)
  • Medicinal Preparation (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Compounds Of Unknown Constitution (AREA)
  • Saccharide Compounds (AREA)
  • Optical Integrated Circuits (AREA)
US09/852,918 2000-05-11 2001-05-10 Recombinant human CLN2 protein and methods of its production and use Abandoned US20020006400A1 (en)

Priority Applications (15)

Application Number Priority Date Filing Date Title
US09/852,918 US20020006400A1 (en) 2000-05-11 2001-05-10 Recombinant human CLN2 protein and methods of its production and use
AU2001263085A AU2001263085A1 (en) 2000-05-11 2001-05-11 Recombinant human cln2 protein and methods of its production and use
BR0110746-1A BR0110746A (pt) 2000-05-11 2001-05-11 Proteìna cln2 recombinante humana e processos de produção e uso da mesma
JP2001581853A JP4843774B2 (ja) 2000-05-11 2001-05-11 組換えヒトｃｌｎ２タンパク質およびその生成方法ならびに使用
AT01937337T ATE360438T1 (de) 2000-05-11 2001-05-11 Verwendung von inaktives cln2 proenzym zur behandlung von lincl
DE60128084T DE60128084T2 (de) 2000-05-11 2001-05-11 Verwendung von inaktivem CLN2-Proenzym zur Behandlung von LINCL
PCT/US2001/015386 WO2001085200A2 (en) 2000-05-11 2001-05-11 Recombinant human cln2 protein and methods of its production and use
MXPA02011162A MXPA02011162A (es) 2000-05-11 2001-05-11 Proteina cln2 recombinante de humano y metodos para su reduccion y uso.
CA2408380A CA2408380C (en) 2000-05-11 2001-05-11 Recombinant human cln2 protein and methods of its production and use
EP01937337A EP1292326B1 (de) 2000-05-11 2001-05-11 Verwendung von inaktives cln2 proenzym zur behandlung von lincl
US10/255,317 US20030091554A1 (en) 2001-05-10 2002-09-26 Recombinant human CLN2 protein and methods of its production and use
US11/507,945 US7811559B2 (en) 2000-05-11 2006-08-22 Methods of reducing storage products using tripeptidyl peptidase I (CLN2) protein
US12/881,066 US8029781B2 (en) 2000-05-11 2010-09-13 Methods of treating a deficiency of functional tripeptidyl peptidase I (CLN2) protein
US13/220,572 US8277800B2 (en) 2000-05-11 2011-08-29 Methods of treating a deficiency of functional tripeptidyl peptidase I (CLN2) protein
US13/598,556 US20130273018A1 (en) 2000-05-11 2012-08-29 Recombinant human cln2 protein and methods of its production and use

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US20340700P 2000-05-11 2000-05-11
US09/852,918 US20020006400A1 (en) 2000-05-11 2001-05-10 Recombinant human CLN2 protein and methods of its production and use

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US10/255,317 Continuation US20030091554A1 (en) 2000-05-11 2002-09-26 Recombinant human CLN2 protein and methods of its production and use

Publications (1)

Publication Number Publication Date
US20020006400A1 true US20020006400A1 (en) 2002-01-17

Family

ID=26898578

Family Applications (5)

Application Number Title Priority Date Filing Date
US09/852,918 Abandoned US20020006400A1 (en) 2000-05-11 2001-05-10 Recombinant human CLN2 protein and methods of its production and use
US11/507,945 Expired - Lifetime US7811559B2 (en) 2000-05-11 2006-08-22 Methods of reducing storage products using tripeptidyl peptidase I (CLN2) protein
US12/881,066 Expired - Fee Related US8029781B2 (en) 2000-05-11 2010-09-13 Methods of treating a deficiency of functional tripeptidyl peptidase I (CLN2) protein
US13/220,572 Expired - Fee Related US8277800B2 (en) 2000-05-11 2011-08-29 Methods of treating a deficiency of functional tripeptidyl peptidase I (CLN2) protein
US13/598,556 Abandoned US20130273018A1 (en) 2000-05-11 2012-08-29 Recombinant human cln2 protein and methods of its production and use

Family Applications After (4)

Application Number Title Priority Date Filing Date
US11/507,945 Expired - Lifetime US7811559B2 (en) 2000-05-11 2006-08-22 Methods of reducing storage products using tripeptidyl peptidase I (CLN2) protein
US12/881,066 Expired - Fee Related US8029781B2 (en) 2000-05-11 2010-09-13 Methods of treating a deficiency of functional tripeptidyl peptidase I (CLN2) protein
US13/220,572 Expired - Fee Related US8277800B2 (en) 2000-05-11 2011-08-29 Methods of treating a deficiency of functional tripeptidyl peptidase I (CLN2) protein
US13/598,556 Abandoned US20130273018A1 (en) 2000-05-11 2012-08-29 Recombinant human cln2 protein and methods of its production and use

Country Status (10)

Country Link
US (5) US20020006400A1 (de)
EP (1) EP1292326B1 (de)
JP (1) JP4843774B2 (de)
AT (1) ATE360438T1 (de)
AU (1) AU2001263085A1 (de)
BR (1) BR0110746A (de)
CA (1) CA2408380C (de)
DE (1) DE60128084T2 (de)
MX (1) MXPA02011162A (de)
WO (1) WO2001085200A2 (de)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20120315263A1 (en) * 2011-06-10 2012-12-13 Olmstead Stephen F Pharmaceutical compositions containing protease and methods for the treatment of lysosomal storage diseases

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7442372B2 (en) 2003-08-29 2008-10-28 Biomarin Pharmaceutical Inc. Delivery of therapeutic compounds to the brain and other tissues
ES2432653B1 (es) * 2012-05-23 2015-09-17 Centro De Investigacion Biomedica En Red De Enfermedades Raras Un procedimiento y kit para el diagnostico diferencial de una enfermedad que cursa con afectación muscular.
TWI752907B (zh) * 2015-05-08 2022-01-21 美商拜奧馬林製藥公司 用於治療cln2疾病之tpp1調配物及方法
AU2020336984B2 (en) 2019-08-29 2026-04-23 Biomarin Pharmaceutical Inc. Methods for treating CLN2 disease in pediatric subjects
JP2025515567A (ja) * 2022-04-06 2025-05-20 ラトガーズ、ザ ステイト ユニバーシティ オブ ニュージャージー ライソゾーム蓄積症を治療するための方法
WO2025221877A1 (en) 2024-04-17 2025-10-23 Five Prime Sciences Incorporated Tripeptidyl peptidase 1-related compositions and methods for the treatment and diagnosis of amyotrophic lateral sclerosis

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6302685B1 (en) * 1997-09-16 2001-10-16 University Of Medicine And Dentistry Of New Jersey Human lysosomal protein and methods of its use

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20120315263A1 (en) * 2011-06-10 2012-12-13 Olmstead Stephen F Pharmaceutical compositions containing protease and methods for the treatment of lysosomal storage diseases
US9387236B2 (en) * 2011-06-10 2016-07-12 Prothera Inc. Pharmaceutical compositions containing protease and methods for the treatment of lysosomal storage diseases

Also Published As

Publication number Publication date
DE60128084T2 (de) 2008-01-03
US20130273018A1 (en) 2013-10-17
ATE360438T1 (de) 2007-05-15
EP1292326B1 (de) 2007-04-25
US8277800B2 (en) 2012-10-02
US20120014935A1 (en) 2012-01-19
CA2408380A1 (en) 2001-11-15
WO2001085200A3 (en) 2002-04-11
US7811559B2 (en) 2010-10-12
EP1292326A2 (de) 2003-03-19
JP4843774B2 (ja) 2011-12-21
US20110014172A1 (en) 2011-01-20
CA2408380C (en) 2012-04-17
US20090022701A1 (en) 2009-01-22
JP2004519415A (ja) 2004-07-02
WO2001085200A2 (en) 2001-11-15
DE60128084D1 (de) 2007-06-06
BR0110746A (pt) 2003-07-22
AU2001263085A1 (en) 2001-11-20
US8029781B2 (en) 2011-10-04
MXPA02011162A (es) 2003-07-28

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AS Assignment

Owner name: MEDICINE AND DENTISTRY OF NEW JERSEY, UNIVERSITY O

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:LOBEL, PETER;REEL/FRAME:012064/0135

Effective date: 20010727

STCB Information on status: application discontinuation

Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION

AS Assignment

Owner name: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF

Free format text: EXECUTIVE ORDER 9424, CONFIRMATORY LICENSE;ASSIGNOR:UNIVERSITY OF MED/DENT NJ NEWARK;REEL/FRAME:020873/0290

Effective date: 20011227