MX2015016263A - Polipeptidos que comprenden una secuencia de aminoacidos de bacteriofago modificado g3p con inmunogenicidad reducida. - Google Patents

Polipeptidos que comprenden una secuencia de aminoacidos de bacteriofago modificado g3p con inmunogenicidad reducida.

Info

Publication number
MX2015016263A
MX2015016263A MX2015016263A MX2015016263A MX2015016263A MX 2015016263 A MX2015016263 A MX 2015016263A MX 2015016263 A MX2015016263 A MX 2015016263A MX 2015016263 A MX2015016263 A MX 2015016263A MX 2015016263 A MX2015016263 A MX 2015016263A
Authority
MX
Mexico
Prior art keywords
polypeptides
amino acid
acid sequence
reduced immunogenicity
modified bacteriophage
Prior art date
Application number
MX2015016263A
Other languages
English (en)
Spanish (es)
Inventor
Timothy David Jones
Robert George Edward Holgate
Francis Joseph Carr
Richard A Fisher
Original Assignee
Neurophage Pharmaceuticals Inc
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Neurophage Pharmaceuticals Inc filed Critical Neurophage Pharmaceuticals Inc
Publication of MX2015016263A publication Critical patent/MX2015016263A/es

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
    • C07K14/01—DNA viruses
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0085—Brain, e.g. brain implants; Spinal cord
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A61P21/04—Drugs for disorders of the muscular or neuromuscular system for myasthenia gravis
    • 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
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • 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
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs
    • 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
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
    • C07K14/4711—Alzheimer's disease; Amyloid plaque core protein
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70503—Immunoglobulin superfamily
    • C07K14/70514—CD4
    • 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
    • C12N7/00—Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
    • 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
    • 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
    • C12N2795/00—Bacteriophages
    • C12N2795/00011—Details
    • C12N2795/14011—Details ssDNA Bacteriophages
    • C12N2795/14111—Inoviridae
    • C12N2795/14122—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
    • 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
    • C12N2795/00—Bacteriophages
    • C12N2795/00011—Details
    • C12N2795/14011—Details ssDNA Bacteriophages
    • C12N2795/14111—Inoviridae
    • C12N2795/14133—Use of viral protein as therapeutic agent other than vaccine, e.g. apoptosis inducing or anti-inflammatory

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Genetics & Genomics (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biochemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Biophysics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Molecular Biology (AREA)
  • Neurosurgery (AREA)
  • Immunology (AREA)
  • Zoology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Virology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Toxicology (AREA)
  • Psychology (AREA)
  • Epidemiology (AREA)
  • Wood Science & Technology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Cell Biology (AREA)
  • Biotechnology (AREA)
  • General Engineering & Computer Science (AREA)
  • Dermatology (AREA)
  • Microbiology (AREA)
  • Hospice & Palliative Care (AREA)
  • Psychiatry (AREA)
  • Physical Education & Sports Medicine (AREA)
MX2015016263A 2013-05-28 2014-05-28 Polipeptidos que comprenden una secuencia de aminoacidos de bacteriofago modificado g3p con inmunogenicidad reducida. MX2015016263A (es)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201361828004P 2013-05-28 2013-05-28
US201361828497P 2013-05-29 2013-05-29
PCT/US2014/039760 WO2014193935A1 (en) 2013-05-28 2014-05-28 Polypeptides comprising a modified bacteriophage g3p amino acid sequence with reduced immunogenicity

Publications (1)

Publication Number Publication Date
MX2015016263A true MX2015016263A (es) 2016-04-18

Family

ID=51168338

Family Applications (1)

Application Number Title Priority Date Filing Date
MX2015016263A MX2015016263A (es) 2013-05-28 2014-05-28 Polipeptidos que comprenden una secuencia de aminoacidos de bacteriofago modificado g3p con inmunogenicidad reducida.

Country Status (13)

Country Link
US (2) US9988444B2 (https=)
EP (1) EP3003349B1 (https=)
JP (1) JP2016526044A (https=)
KR (1) KR20160010618A (https=)
CN (1) CN105473153A (https=)
AU (1) AU2014274253B2 (https=)
CA (1) CA2913414A1 (https=)
EA (1) EA030389B1 (https=)
HK (1) HK1223285A1 (https=)
MX (1) MX2015016263A (https=)
PH (1) PH12015502585A1 (https=)
SG (1) SG11201509647WA (https=)
WO (1) WO2014193935A1 (https=)

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2857539C (en) 2011-11-29 2021-08-03 Neurophage Pharmaceuticals, Inc. Bacteriophage gene 3 protein compositions and use as amyloid binding agents
DK2906235T3 (en) 2012-10-02 2017-09-25 Proclara Biosciences Inc USE OF P3 OF BACTERIOPHAGIC FUSION PROTEINS AS AMYLOID BINDING AGENTS
BR112017011530A2 (pt) 2014-12-03 2018-03-13 Proclara Biosciences Inc polipeptídeos que compreendem uma sequência de aminoácidos g3p de bacteriófago modificada sem sinal de glicosilação
CN107384960B (zh) * 2017-07-25 2020-06-12 吉优诺（上海）基因科技有限公司 基于复制缺陷性重组腺病毒携带il-17结合分子转基因载体及其构建方法和应用
WO2019241628A1 (en) 2018-06-15 2019-12-19 Proclara Biosciences, Inc. General amyloid interaction motif (gaim)
US20240124889A1 (en) 2019-05-07 2024-04-18 Voyager Therapeutics, Inc. Compositions and methods for the vectored augmentation of protein destruction, expression and/or regulation
EP4185567A4 (en) 2020-07-24 2024-08-14 Jawaharlal Nehru Centre For Advanced Scientific Research NAPHTHALENE MONOIMIDE COMPOUNDS AND RELATED METHODS
CN114057858B (zh) 2020-08-10 2023-03-21 上海瑞吉康生物医药有限公司 对引起神经变性和神经退行性疾病的蛋白聚集具有解聚作用的多肽
AU2023403257A1 (en) 2022-12-02 2025-06-12 Alzheon, Inc. Methods for treating neurodegenerative disorders with tramiprosate

Family Cites Families (32)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3941763A (en) 1975-03-28 1976-03-02 American Home Products Corporation PGlu-D-Met-Trp-Ser-Tyr-D-Ala-Leu-Arg-Pro-Gly-NH2 and intermediates
US4215051A (en) 1979-08-29 1980-07-29 Standard Oil Company (Indiana) Formation, purification and recovery of phthalic anhydride
DE3572982D1 (en) 1984-03-06 1989-10-19 Takeda Chemical Industries Ltd Chemically modified lymphokine and production thereof
WO1990006952A1 (fr) 1988-12-22 1990-06-28 Kirin-Amgen, Inc. Facteur de stimulation de colonies de granulocytes modifies chimiquement
EP0939121B2 (de) 1989-09-12 2007-12-26 AHP Manufacturing B.V. TFN-bindende Proteine
US6552170B1 (en) 1990-04-06 2003-04-22 Amgen Inc. PEGylation reagents and compounds formed therewith
US5252714A (en) 1990-11-28 1993-10-12 The University Of Alabama In Huntsville Preparation and use of polyethylene glycol propionaldehyde
ATE240740T1 (de) 1991-03-15 2003-06-15 Amgen Inc Pegylation von polypeptiden
JP3068301B2 (ja) * 1992-01-08 2000-07-24 三菱電機株式会社 Ｉｃカード内のコネクタ支持固定機構
FR2686899B1 (fr) 1992-01-31 1995-09-01 Rhone Poulenc Rorer Sa Nouveaux polypeptides biologiquement actifs, leur preparation et compositions pharmaceutiques les contenant.
ATE311895T1 (de) 1992-05-26 2005-12-15 Immunex Corp Neue zytokine die cd30 binden
EP0983303B1 (en) 1997-05-21 2006-03-08 Biovation Limited Method for the production of non-immunogenic proteins
AU776910B2 (en) 1998-12-08 2004-09-23 Merck Patent Gesellschaft Mit Beschrankter Haftung Modifying protein immunogenicity
US20020052311A1 (en) 1999-09-03 2002-05-02 Beka Solomon Methods and compostions for the treatment and/or diagnosis of neurological diseases and disorders
US8022270B2 (en) 2000-07-31 2011-09-20 Biolex Therapeutics, Inc. Expression of biologically active polypeptides in duckweed
CN100522242C (zh) 2001-02-19 2009-08-05 默克专利有限公司 具有降低的免疫原性的人工蛋白质
KR20030082962A (ko) 2001-03-08 2003-10-23 메르크 파텐트 게엠베하 감소된 면역원성을 갖는 개질된과립구대식세포집락자극인자(ｇｍ-ｃｓｆ)
DE10238846A1 (de) 2002-08-20 2004-03-04 Nemod Immuntherapie Ag Aktive Fusionsproteine und Verfahren zu ihrer Herstellung
DK1853285T3 (da) * 2005-02-01 2011-06-27 Univ Ramot Fremgangsmåde til behandling af inflammation forbundet med amyloidaflejringer og hjerneinflammation som involverer aktiverede mikroglia
EP1991261A2 (en) 2006-02-15 2008-11-19 Ramot at Tel-Aviv University Ltd. Filamentous bacteriophage displaying protein as a binder of antibodies and immunocomplexes for delivery to the brain
US20090304726A1 (en) 2006-02-15 2009-12-10 Ramot At Tel Aviv University Ltd. Viral display vehicles for treating multiple sclerosis
WO2007109733A2 (en) 2006-03-21 2007-09-27 The Johns Hopkins University Diagnostic and prognostic markers and treatment strategies for multiple sclerosis
US20090105090A1 (en) 2006-04-06 2009-04-23 Fumiaki Uchiyama Phage Display By Novel Filamentous Bacteriophage
AU2007275258A1 (en) 2006-07-21 2008-01-24 Ramot At Tel Aviv University Ltd. Use of a phage displaying a peptide from an adhesion protein for treating a disease associated with intracellular formation of protein fibrillar inclusions or aggregates
KR101485202B1 (ko) 2006-10-11 2015-01-22 안티토페 리미티드 Ｔ 세포 에피토프 데이터베이스들
EP2303315A1 (en) 2008-05-22 2011-04-06 Ramot at Tel Aviv University Ltd. Method for treating disease characterized by plaque
NZ592928A (en) 2008-11-24 2012-12-21 Univ Ramot Method for treating parkinson' s disease using filamentous bacteriophage
WO2011084714A2 (en) 2009-12-17 2011-07-14 Biogen Idec Ma Inc. STABILIZED ANTI-TNF-ALPHA scFv MOLECULES OR ANTI-TWEAK scFv MOLECULES AND USES THEREOF
WO2012125555A1 (en) 2011-03-11 2012-09-20 Ramot At Tel-Aviv University Ltd. Method for treating neurodegenerative tauopathy
CA2857539C (en) * 2011-11-29 2021-08-03 Neurophage Pharmaceuticals, Inc. Bacteriophage gene 3 protein compositions and use as amyloid binding agents
DK2906235T3 (en) 2012-10-02 2017-09-25 Proclara Biosciences Inc USE OF P3 OF BACTERIOPHAGIC FUSION PROTEINS AS AMYLOID BINDING AGENTS
BR112017011530A2 (pt) 2014-12-03 2018-03-13 Proclara Biosciences Inc polipeptídeos que compreendem uma sequência de aminoácidos g3p de bacteriófago modificada sem sinal de glicosilação

Also Published As

Publication number Publication date
JP2016526044A (ja) 2016-09-01
WO2014193935A1 (en) 2014-12-04
US20180251534A1 (en) 2018-09-06
CN105473153A (zh) 2016-04-06
AU2014274253B2 (en) 2018-06-14
AU2014274253A1 (en) 2016-01-21
EA030389B1 (ru) 2018-07-31
PH12015502585A1 (en) 2016-02-29
KR20160010618A (ko) 2016-01-27
EP3003349A1 (en) 2016-04-13
HK1223285A1 (zh) 2017-07-28
CA2913414A1 (en) 2014-12-04
EA201592272A1 (ru) 2016-04-29
EP3003349B1 (en) 2018-12-12
US20170129945A9 (en) 2017-05-11
US9988444B2 (en) 2018-06-05
US20160115223A1 (en) 2016-04-28
SG11201509647WA (en) 2015-12-30

Similar Documents

Publication Publication Date Title
PH12015502585A1 (en) Polypeptides comprising a modified bacteriophage g3p amino acid sequence with reduced immunogenicity
PH12017501004A1 (en) Polypeptides comprising a modified bacteriophage g3p amino acid sequence lacking a glycosylation signal
SA518390954B1 (ar) لقاحات علاجية لفيروس الورم الحليمي البشري 18
MX361728B (es) Ácido nucleico que comprende o codifica un tallo-bucle de histona y una secuencia poli(a) o una señal de poliadenilación para incrementar la expresión de un antígeno tumoral codificado.
MY196882A (en) Recombinant binding proteins and their use
MX359953B (es) Ácido nucleico que comprende o que codifica un tallo-rizo de histona y una secuencia poli (a) o una señal de poliadenilación para incrementar la expresión de una proteína terapéutica codificada.
MX2022005291A (es) Vacunas para el tratamiento y prevencion del cancer.
WO2013120628A8 (en) Nucleic acid comprising or coding for a histone stem-loop and a poly(a) sequence or a polyadenylation signal for increasing the expression of an encoded pathogenic antigen
PH12017500032B1 (en) Improved a㟠protofibril binding antibodies
NZ703597A (en) Mutant fragments of ospa and methods and uses relating thereto
NZ721015A (en) Mutant fragments of ospa and methods and uses relating thereto
PH12017500450A1 (en) Flavivirus virus like particle
MX2014004953A (es) Ligadores basados en tirosina para la conexion desprendible de peptidos.
GB201118201D0 (en) Novel peptides
EP4406613A3 (en) Immunogenic arginase peptides
MX2018001964A (es) Polipeptidos mrka, anticuerpos y usos de los mismos.
MX2016005976A (es) Formulaciones de tripeptido liofilizado estables en almacenamiento.
MX2016012428A (es) Aumento de la expresion de proteina recombinante con cobre.
IL287987A (en) Improved dried formulations relating to hyaluronic acid and plasmatic proteins, and their uses
MX2015011064A (es) Vacuna contra el virus de la leucemia bovina.
WO2015132103A3 (en) Polypeptides derived from enterococcus and their use for vaccination and the generation of therapeutic antibodies
PH12016501608A1 (en) Peptides and methods of use
HK1232900A1 (en) IMPROVED Aß PROTOFIBRIL BINDING ANTIBODIES