ME03667B - Metodi lečenja tauopatije - Google Patents

Metodi lečenja tauopatije

Info

Publication number
ME03667B
ME03667B MEP-2020-44A MEP202044A ME03667B ME 03667 B ME03667 B ME 03667B ME P202044 A MEP202044 A ME P202044A ME 03667 B ME03667 B ME 03667B
Authority
ME
Montenegro
Prior art keywords
gly
ser
pro
lys
ala
Prior art date
Application number
MEP-2020-44A
Other languages
German (de)
English (en)
French (fr)
Inventor
Irene Griswold-Prenner
Nancy E Stagliano
Vu Dang
Original Assignee
Ipierian 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 Ipierian Inc filed Critical Ipierian Inc
Publication of ME03667B publication Critical patent/ME03667B/me

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    • 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
    • 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
    • A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
    • A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
    • 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
    • A61K47/56—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 organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
    • A61K47/59—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 organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
    • A61K47/60—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 organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
    • 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
    • A61K47/62—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 a protein, peptide or polyamino acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
    • A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
    • A61K51/04—Organic compounds
    • A61K51/08—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins
    • A61K51/10—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody
    • 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
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/46—Hybrid immunoglobulins
    • C07K16/461—Igs containing Ig-regions, -domains or -residues form different species
    • 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
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
    • G01N33/6896—Neurological disorders, e.g. Alzheimer's disease
    • 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
    • C07K2317/20—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
    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/34—Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C07K2317/565—Complementarity determining region [CDR]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C07K2317/567—Framework region [FR]
    • 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
    • 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
    • C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
    • C07K2319/10—Fusion polypeptide containing a localisation/targetting motif containing a tag for extracellular membrane crossing, e.g. TAT or VP22
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
    • G01N2333/46—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans from vertebrates
    • G01N2333/47—Assays involving proteins of known structure or function as defined in the subgroups
    • G01N2333/4701—Details
    • G01N2333/4709—Amyloid plaque core protein
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/52—Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis

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  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Immunology (AREA)
  • Biomedical Technology (AREA)
  • Molecular Biology (AREA)
  • Organic Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biochemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Genetics & Genomics (AREA)
  • Hematology (AREA)
  • Urology & Nephrology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Microbiology (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Biophysics (AREA)
  • Epidemiology (AREA)
  • Biotechnology (AREA)
  • Physics & Mathematics (AREA)
  • Cell Biology (AREA)
  • Food Science & Technology (AREA)
  • Analytical Chemistry (AREA)
  • General Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Mycology (AREA)
  • Endocrinology (AREA)
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Description

METODI LEČENJA TAUOPATIJE
LISTING SEKVENCI
[0440]
<110> Griswold-Prenner, Irene
Stagliano, Nancy E.
Dang, Vu
<120> METODI LEČENJA TAUOPATIJE
<130> IPRN-745WO
<150> US 61/833,355
<151> 2013-06-10
<150> US 61/833,355
<151> 2013-04-19
<150> US 61/833,355
<151> 2013-03-14
<150> US 61/754,085
<151> 2013-01-18
<150> US 61/683,902
<151> 2012-08-16
<160> 86
<170> PatentIn verzija 3.5
<210> 1
<211> 16
<212> PRT
<213> Veštačka sekvenca
<220>
<223> Sintetička aminokiselinska sekvenca
<400> 1
Arg Ser Ser Gln Thr Ile Leu His Ser Asn Gly Asn Thr Tyr Leu Glu
1 5 10 15
<210> 2
<211> 7
<212> PRT
<213> Veštačka sekvenca
<220>
<223> Sintetička aminokiselinska sekvenca
<400> 2
Lys Val Ser Lys Arg Phe Ser
1 5
<210> 3
<211> 9
<212> PRT
<213> Veštačka sekvenca
<220>
<223> Sintetička aminokiselinska sekvenca
<400> 3
Phe Gln Gly Ser Leu Val Pro Trp Ala
1 5
<210> 4
<211> 5
<212> PRT
<213> Veštačka sekvenca
<220>
<223> Sintetička aminokiselinska sekvenca
<400> 4
Ser Tyr Gly Met Ser
1 5
<210> 5
<211> 17
<212> PRT
<213> Veštačka sekvenca
<220>
<223> Sintetička aminokiselinska sekvenca
<400> 5
Thr Ile Ser Ser Ser Gly Ser Arg Thr Tyr Phe Pro Asp Ser Val Lys
1 5 10 15
Gly
<210> 6
<211> 8
<212> PRT
<213> Veštačka sekvenca
<220>
<223> Sintetička aminokiselinska sekvenca
<400> 6
Thr Trp Asp Gly Ala Met Asp Tyr
1 5
<210> 7
<211> 16
<212> PRT
<213> Veštačka sekvenca
<220>
<223> Sintetička aminokiselinska sekvenca
<400> 7
Lys Ser Ser Gln Ser Ile Val His Ser Asn Gly Asn Thr Tyr Leu Glu
1 5 10 15
<210> 8
<211> 7
<212> PRT
<213> Veštačka sekvenca
<220>
<223> Sintetička aminokiselinska sekvenca
<400> 8
Lys Val Ser Asn Arg Phe Ser
1 5
<210> 9
<211> 9
<212> PRT
<213> Veštačka sekvenca
<220>
<223> Sintetička aminokiselinska sekvenca
<400> 9
Phe Gln Gly Ser Leu Val Pro Trp Ala
1 5
<210> 10
<211> 5
<212> PRT
<213> Veštačka sekvenca
<220>
<223> Sintetička aminokiselinska sekvenca
<400> 10
Lys Tyr Gly Met Ser
1 5
<210> 11
<211> 17
<212> PRT
<213> Veštačka sekvenca
<220>
<223> Sintetička aminokiselinska sekvenca
<400> 11
Thr Ile Ser Ser Ser Gly Ser Arg Thr Tyr Tyr Pro Asp Ser Val Lys
1 5 10 15
Gly
<210> 12
<211> 8
<212> PRT
<213> Veštačka sekvenca
<220>
<223> Sintetička aminokiselinska sekvenca
<400> 12
Ser Trp Asp Gly Ala Met Asp Tyr
1 5
<210> 13
<211> 112
<212> PRT
<213> Veštačka sekvenca
<220>
<223> Sintetička aminokiselinska sekvenca
<400> 13
Asp Val Leu Met Thr Gln Thr Pro Leu Ser Leu Ala Val Asn Leu Gly
1 5 10 15
Asp Gln Ala Ser Leu Ser Cys Arg Ser Ser Gln Thr Ile Leu His Ser
20 25 30
Asn Gly Asn Thr Tyr Leu Glu Trp Tyr Leu Gln Lys Pro Gly Gln Ser
35 40 45
Pro Arg Leu Leu Ile Tyr Lys Val Ser Lys Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Asp Asp Leu Gly Ile Tyr Tyr Cys Phe Gln Gly
85 90 95
Ser Leu Val Pro Trp Ala Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys
100 105 110
<210> 14
<211> 117
<212> PRT
<213> Veštačka sekvenca
<220>
<223> Sintetička aminokiselinska sekvenca
<400> 14
Glu Val Gln Leu Val Glu Ser Gly Glu Asp Leu Val Lys Pro Gly Gly
1 5 10 15
Ser Leu Lys Leu Ser Cys Val Ala Ser Gly Phe Ala Phe Ser Ser Tyr
20 25 30
Gly Met Ser Trp Val Arg Gln Thr Pro Asp Met Arg Leu Glu Trp Val
35 40 45
Ala Thr Ile Ser Ser Ser Gly Ser Arg Thr Tyr Phe Pro Asp Ser Val
50 55 60
Lys Gly Arg Leu Thr Ile Ser Arg Asp Asn Asp Lys Asn Ile Leu Tyr
65 70 75 80
Leu Gln Met Ser Ser Leu Arg Ser Glu Asp Thr Ala Met Tyr Tyr Cys
85 90 95
Thr Ile Thr Trp Asp Gly Ala Met Asp Tyr Trp Gly Arg Gly Ile Ser
100 105 110
Val Thr Val Ser Ser
115
<210> 15
<211> 112
<212> PRT
<213> Veštačka sekvenca
<220>
<223> Sintetička aminokiselinska sekvenca
<400> 15
Asp Val Leu Met Thr Gln Thr Pro Leu Ser Leu Pro Val Ser Leu Gly
1 5 10 15
Asp Gln Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Ile Val His Ser
20 25 30
Asn Gly Asn Thr Tyr Leu Glu Trp Tyr Leu Gln Lys Pro Gly Gln Ser
35 40 45
Pro Lys Leu Leu Val Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Leu Gly Thr Tyr Tyr Cys Phe Gln Gly
85 90 95
Ser Leu Val Pro Trp Ala Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys
100 105 110
<210> 16
<211> 117
<212> PRT
<213> Veštačka sekvenca
<220>
<223> Sintetička aminokiselinska sekvenca
<400> 16
Glu Val His Leu Val Glu Ser Gly Gly Ala Leu Val Lys Pro Gly Gly
1 5 10 15
Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Ser Phe Ser Lys Tyr
20 25 30
Gly Met Ser Trp Val Arg Gln Thr Pro Asp Lys Arg Leu Glu Trp Val
35 40 45
Ala Thr Ile Ser Ser Ser Gly Ser Arg Thr Tyr Tyr Pro Asp Ser Val
50 55 60
Lys Gly Gln Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Ser Ser Leu Lys Ser Glu Asp Thr Ala Met Tyr Tyr Cys
85 90 95
Ser Ile Ser Trp Asp Gly Ala Met Asp Tyr Trp Gly Gln Gly Thr Ser
100 105 110
Val Thr Val Ser Ser
115
<210> 17
<211> 336
<212> DNK
<213> Veštačka sekvenca
<220>
<223> Sintetička sekvenca nukleinske kiseline
<400> 17
gatgttttga tgacccaaac tccgctctcc ctggcagtca atcttggaga tcaagcctcc 60
ctctcttgca gatcgagtca gactatttta catagtaatg gaaataccta tttagaatgg 120
tatttgcaga aaccaggcca gtctccaaga ctcctgatct acaaagtttc taaacgattt 180
tctggggtcc cagacaggtt cagtggcagt ggatcaggga cagatttcac actcaagatc 240
agcagagtgg aggctgacga tctgggaatt tattactgct ttcaaggttc acttgttcct 300
tgggcgttcg gtggaggcac caagctggaa atcaaa 336
<210> 18
<211> 351
<212> DNK
<213> Veštačka sekvenca
<220>
<223> Sintetička sekvenca nukleinske kiseline
<400> 18
gaggtgcagt tggtggagtc tggggaagac ttagtgaagc ctggagggtc cctgaaactc 60
tcctgtgtcg cttctggatt cgctttcagt agctatggca tgtcttgggt tcgccagact 120
ccagacatga ggctggagtg ggtcgcaaca attagtagca gtggtagtcg cacctacttt 180
ccagacagtg tgaaggggcg actcaccatc tccagagaca atgacaagaa catcctatac 240
ctacaaatga gcagtctgag gtctgaggac acagccatgt actattgtac gattacctgg 300
gacggtgcta tggactactg gggtcgtgga atatcagtca ccgtctcctc a 351
<210> 19
<211> 336
<212> DNK
<213> Veštačka sekvenca
<220>
<223> Sintetička sekvenca nukleinske kiseline
<400> 19
gatgttttga tgacccaaac tccactctcc ctgcctgtca gtcttggaga tcaagcctcc 60
atctcttgca aatctagtca gagcattgta catagtaatg gaaacaccta tttagaatgg 120
tacctgcaga aaccaggcca gtctccaaag ctcctggtct acaaagtttc caatcgattt 180
tctggggtcc cagacaggtt cagtggcagt ggatcaggga cagatttcac actcaagatc 240
agcagagtgg aggctgagga tctgggaact tattactgct ttcaaggttc acttgttcct 300
tgggcgttcg gtggaggcac caagctggaa atcaaa 336
<210> 20
<211> 351
<212> DNK
<213> Veštačka sekvenca
<220>
<223> Sintetička sekvenca nukleinske kiseline
<400> 20
gaggttcatc tggtggagtc tgggggagcc ttagtgaagc ctggagggtc cctgaaactc 60
tcctgtgcag cctctggatt cagtttcagt aaatatggca tgtcttgggt tcgccagact 120
ccagacaaga ggctggagtg ggtcgcaacc attagtagta gtgggagtcg cacctactat 180
ccagacagtg tgaagggcca attcaccatc tccagagaca atgccaagaa caccctgtac 240
ctgcaaatga gcagtctgaa gtctgaggac acagccatgt attactgttc aattagctgg 300
gacggtgcta tggactactg gggtcaaggg acctcagtca ccgtctcctc a 351
<210> 21
<211> 441
<212> PRT
<213> Veštačka sekvenca
<220>
<223> Sintetička aminokiselinska sekvenca
<400> 21
Met Ala Glu Pro Arg Gln Glu Phe Glu Val Met Glu Asp His Ala Gly
1 5 10 15
Thr Tyr Gly Leu Gly Asp Arg Lys Asp Gln Gly Gly Tyr Thr Met His
20 25 30
Gln Asp Gln Glu Gly Asp Thr Asp Ala Gly Leu Lys Glu Ser Pro Leu
35 40 45
Gln Thr Pro Thr Glu Asp Gly Ser Glu Glu Pro Gly Ser Glu Thr Ser
50 55 60
Asp Ala Lys Ser Thr Pro Thr Ala Glu Asp Val Thr Ala Pro Leu Val
65 70 75 80
Asp Glu Gly Ala Pro Gly Lys Gln Ala Ala Ala Gln Pro His Thr Glu
85 90 95
Ile Pro Glu Gly Thr Thr Ala Glu Glu Ala Gly Ile Gly Asp Thr Pro
100 105 110
Ser Leu Glu Asp Glu Ala Ala Gly His Val Thr Gln Ala Arg Met Val
115 120 125
Ser Lys Ser Lys Asp Gly Thr Gly Ser Asp Asp Lys Lys Ala Lys Gly
130 135 140
Ala Asp Gly Lys Thr Lys Ile Ala Thr Pro Arg Gly Ala Ala Pro Pro
145 150 155 160
Gly Gln Lys Gly Gln Ala Asn Ala Thr Arg Ile Pro Ala Lys Thr Pro
165 170 175
Pro Ala Pro Lys Thr Pro Pro Ser Ser Gly Glu Pro Pro Lys Ser Gly
180 185 190
Asp Arg Ser Gly Tyr Ser Ser Pro Gly Ser Pro Gly Thr Pro Gly Ser
195 200 205
Arg Ser Arg Thr Pro Ser Leu Pro Thr Pro Pro Thr Arg Glu Pro Lys
210 215 220
Lys Val Ala Val Val Arg Thr Pro Pro Lys Ser Pro Ser Ser Ala Lys
225 230 235 240
Ser Arg Leu Gln Thr Ala Pro Val Pro Met Pro Asp Leu Lys Asn Val
245 250 255
Lys Ser Lys Ile Gly Ser Thr Glu Asn Leu Lys His Gln Pro Gly Gly
260 265 270
Gly Lys Val Gln Ile Ile Asn Lys Lys Leu Asp Leu Ser Asn Val Gln
275 280 285
Ser Lys Cys Gly Ser Lys Asp Asn Ile Lys His Val Pro Gly Gly Gly
290 295 300
Ser Val Gln Ile Val Tyr Lys Pro Val Asp Leu Ser Lys Val Thr Ser
305 310 315 320
Lys Cys Gly Ser Leu Gly Asn Ile His His Lys Pro Gly Gly Gly Gln
325 330 335
Val Glu Val Lys Ser Glu Lys Leu Asp Phe Lys Asp Arg Val Gln Ser
340 345 350
Lys Ile Gly Ser Leu Asp Asn Ile Thr His Val Pro Gly Gly Gly Asn
355 360 365
Lys Lys Ile Glu Thr His Lys Leu Thr Phe Arg Glu Asn Ala Lys Ala
370 375 380
Lys Thr Asp His Gly Ala Glu Ile Val Tyr Lys Ser Pro Val Val Ser
385 390 395 400
Gly Asp Thr Ser Pro Arg His Leu Ser Asn Val Ser Ser Thr Gly Ser
405 410 415
Ile Asp Met Val Asp Ser Pro Gln Leu Ala Thr Leu Ala Asp Glu Val
420 425 430
Ser Ala Ser Leu Ala Lys Gln Gly Leu
435 440
<210> 22
<211> 383
<212> PRT
<213> Veštačka sekvenca
<220>
<223> Sintetička aminokiselinska sekvenca
<400> 22
Met Ala Glu Pro Arg Gln Glu Phe Glu Val Met Glu Asp His Ala Gly
1 5 10 15
Thr Tyr Gly Leu Gly Asp Arg Lys Asp Gln Gly Gly Tyr Thr Met His
20 25 30
Gln Asp Gln Glu Gly Asp Thr Asp Ala Gly Leu Lys Ala Glu Glu Ala
35 40 45
Gly Ile Gly Asp Thr Pro Ser Leu Glu Asp Glu Ala Ala Gly His Val
50 55 60
Thr Gln Ala Arg Met Val Ser Lys Ser Lys Asp Gly Thr Gly Ser Asp
65 70 75 80
Asp Lys Lys Ala Lys Gly Ala Asp Gly Lys Thr Lys Ile Ala Thr Pro
85 90 95
Arg Gly Ala Ala Pro Pro Gly Gln Lys Gly Gln Ala Asn Ala Thr Arg
100 105 110
Ile Pro Ala Lys Thr Pro Pro Ala Pro Lys Thr Pro Pro Ser Ser Gly
115 120 125
Glu Pro Pro Lys Ser Gly Asp Arg Ser Gly Tyr Ser Ser Pro Gly Ser
130 135 140
Pro Gly Thr Pro Gly Ser Arg Ser Arg Thr Pro Ser Leu Pro Thr Pro
145 150 155 160
Pro Thr Arg Glu Pro Lys Lys Val Ala Val Val Arg Thr Pro Pro Lys
165 170 175
Ser Pro Ser Ser Ala Lys Ser Arg Leu Gln Thr Ala Pro Val Pro Met
180 185 190
Pro Asp Leu Lys Asn Val Lys Ser Lys Ile Gly Ser Thr Glu Asn Leu
195 200 205
Lys His Gln Pro Gly Gly Gly Lys Val Gln Ile Ile Asn Lys Lys Leu
210 215 220
Asp Leu Ser Asn Val Gln Ser Lys Cys Gly Ser Lys Asp Asn Ile Lys
225 230 235 240
His Val Pro Gly Gly Gly Ser Val Gln Ile Val Tyr Lys Pro Val Asp
245 250 255
Leu Ser Lys Val Thr Ser Lys Cys Gly Ser Leu Gly Asn Ile His His
260 265 270
Lys Pro Gly Gly Gly Gln Val Glu Val Lys Ser Glu Lys Leu Asp Phe
275 280 285
Lys Asp Arg Val Gln Ser Lys Ile Gly Ser Leu Asp Asn Ile Thr His
290 295 300
Val Pro Gly Gly Gly Asn Lys Lys Ile Glu Thr His Lys Leu Thr Phe
305 310 315 320
Arg Glu Asn Ala Lys Ala Lys Thr Asp His Gly Ala Glu Ile Val Tyr
325 330 335
Lys Ser Pro Val Val Ser Gly Asp Thr Ser Pro Arg His Leu Ser Asn
340 345 350
Val Ser Ser Thr Gly Ser Ile Asp Met Val Asp Ser Pro Gln Leu Ala
355 360 365
Thr Leu Ala Asp Glu Val Ser Ala Ser Leu Ala Lys Gln Gly Leu
370 375 380
<210> 23
<211> 352
<212> PRT
<213> Veštačka sekvenca
<220>
<223> Sintetička aminokiselinska sekvenca
<400> 23
Met Ala Glu Pro Arg Gln Glu Phe Glu Val Met Glu Asp His Ala Gly
1 5 10 15
Thr Tyr Gly Leu Gly Asp Arg Lys Asp Gln Gly Gly Tyr Thr Met His
20 25 30
Gln Asp Gln Glu Gly Asp Thr Asp Ala Gly Leu Lys Ala Glu Glu Ala
35 40 45
Gly Ile Gly Asp Thr Pro Ser Leu Glu Asp Glu Ala Ala Gly His Val
50 55 60
Thr Gln Ala Arg Met Val Ser Lys Ser Lys Asp Gly Thr Gly Ser Asp
65 70 75 80
Asp Lys Lys Ala Lys Gly Ala Asp Gly Lys Thr Lys Ile Ala Thr Pro
85 90 95
Arg Gly Ala Ala Pro Pro Gly Gln Lys Gly Gln Ala Asn Ala Thr Arg
100 105 110
Ile Pro Ala Lys Thr Pro Pro Ala Pro Lys Thr Pro Pro Ser Ser Gly
115 120 125
Glu Pro Pro Lys Ser Gly Asp Arg Ser Gly Tyr Ser Ser Pro Gly Ser
130 135 140
Pro Gly Thr Pro Gly Ser Arg Ser Arg Thr Pro Ser Leu Pro Thr Pro
145 150 155 160
Pro Thr Arg Glu Pro Lys Lys Val Ala Val Val Arg Thr Pro Pro Lys
165 170 175
Ser Pro Ser Ser Ala Lys Ser Arg Leu Gln Thr Ala Pro Val Pro Met
180 185 190
Pro Asp Leu Lys Asn Val Lys Ser Lys Ile Gly Ser Thr Glu Asn Leu
195 200 205
Lys His Gln Pro Gly Gly Gly Lys Val Gln Ile Val Tyr Lys Pro Val
210 215 220
Asp Leu Ser Lys Val Thr Ser Lys Cys Gly Ser Leu Gly Asn Ile His
225 230 235 240
His Lys Pro Gly Gly Gly Gln Val Glu Val Lys Ser Glu Lys Leu Asp
245 250 255
Phe Lys Asp Arg Val Gln Ser Lys Ile Gly Ser Leu Asp Asn Ile Thr
260 265 270
His Val Pro Gly Gly Gly Asn Lys Lys Ile Glu Thr His Lys Leu Thr
275 280 285
Phe Arg Glu Asn Ala Lys Ala Lys Thr Asp His Gly Ala Glu Ile Val
290 295 300
Tyr Lys Ser Pro Val Val Ser Gly Asp Thr Ser Pro Arg His Leu Ser
305 310 315 320
Asn Val Ser Ser Thr Gly Ser Ile Asp Met Val Asp Ser Pro Gln Leu
325 330 335
Ala Thr Leu Ala Asp Glu Val Ser Ala Ser Leu Ala Lys Gln Gly Leu
340 345 350
<210> 24
<211> 412
<212> PRT
<213> Veštačka sekvenca
<220>
<223> Sintetička aminokiselinska sekvenca
<400> 24
Met Ala Glu Pro Arg Gln Glu Phe Glu Val Met Glu Asp His Ala Gly
1 5 10 15
Thr Tyr Gly Leu Gly Asp Arg Lys Asp Gln Gly Gly Tyr Thr Met His
20 25 30
Gln Asp Gln Glu Gly Asp Thr Asp Ala Gly Leu Lys Glu Ser Pro Leu
35 40 45
Gln Thr Pro Thr Glu Asp Gly Ser Glu Glu Pro Gly Ser Glu Thr Ser
50 55 60
Asp Ala Lys Ser Thr Pro Thr Ala Glu Ala Glu Glu Ala Gly Ile Gly
65 70 75 80
Asp Thr Pro Ser Leu Glu Asp Glu Ala Ala Gly His Val Thr Gln Ala
85 90 95
Arg Met Val Ser Lys Ser Lys Asp Gly Thr Gly Ser Asp Asp Lys Lys
100 105 110
Ala Lys Gly Ala Asp Gly Lys Thr Lys Ile Ala Thr Pro Arg Gly Ala
115 120 125
Ala Pro Pro Gly Gln Lys Gly Gln Ala Asn Ala Thr Arg Ile Pro Ala
130 135 140
Lys Thr Pro Pro Ala Pro Lys Thr Pro Pro Ser Ser Gly Glu Pro Pro
145 150 155 160
Lys Ser Gly Asp Arg Ser Gly Tyr Ser Ser Pro Gly Ser Pro Gly Thr
165 170 175
Pro Gly Ser Arg Ser Arg Thr Pro Ser Leu Pro Thr Pro Pro Thr Arg
180 185 190
Glu Pro Lys Lys Val Ala Val Val Arg Thr Pro Pro Lys Ser Pro Ser
195 200 205
Ser Ala Lys Ser Arg Leu Gln Thr Ala Pro Val Pro Met Pro Asp Leu
210 215 220
Lys Asn Val Lys Ser Lys Ile Gly Ser Thr Glu Asn Leu Lys His Gln
225 230 235 240
Pro Gly Gly Gly Lys Val Gln Ile Ile Asn Lys Lys Leu Asp Leu Ser
245 250 255
Asn Val Gln Ser Lys Cys Gly Ser Lys Asp Asn Ile Lys His Val Pro
260 265 270
Gly Gly Gly Ser Val Gln Ile Val Tyr Lys Pro Val Asp Leu Ser Lys
275 280 285
Val Thr Ser Lys Cys Gly Ser Leu Gly Asn Ile His His Lys Pro Gly
290 295 300
Gly Gly Gln Val Glu Val Lys Ser Glu Lys Leu Asp Phe Lys Asp Arg
305 310 315 320
Val Gln Ser Lys Ile Gly Ser Leu Asp Asn Ile Thr His Val Pro Gly
325 330 335
Gly Gly Asn Lys Lys Ile Glu Thr His Lys Leu Thr Phe Arg Glu Asn
340 345 350
Ala Lys Ala Lys Thr Asp His Gly Ala Glu Ile Val Tyr Lys Ser Pro
355 360 365
Val Val Ser Gly Asp Thr Ser Pro Arg His Leu Ser Asn Val Ser Ser
370 375 380
Thr Gly Ser Ile Asp Met Val Asp Ser Pro Gln Leu Ala Thr Leu Ala
385 390 395 400
Asp Glu Val Ser Ala Ser Leu Ala Lys Gln Gly Leu
405 410
<210> 25
<211> 776
<212> PRT
<213> Veštačka sekvenca
<220>
<223> Sintetička aminokiselinska sekvenca
<400> 25
Met Ala Glu Pro Arg Gln Glu Phe Glu Val Met Glu Asp His Ala Gly
1 5 10 15
Thr Tyr Gly Leu Gly Asp Arg Lys Asp Gln Gly Gly Tyr Thr Met His
20 25 30
Gln Asp Gln Glu Gly Asp Thr Asp Ala Gly Leu Lys Glu Ser Pro Leu
35 40 45
Gln Thr Pro Thr Glu Asp Gly Ser Glu Glu Pro Gly Ser Glu Thr Ser
50 55 60
Asp Ala Lys Ser Thr Pro Thr Ala Glu Asp Val Thr Ala Pro Leu Val
65 70 75 80
Asp Glu Gly Ala Pro Gly Lys Gln Ala Ala Ala Gln Pro His Thr Glu
85 90 95
Ile Pro Glu Gly Thr Thr Ala Glu Glu Ala Gly Ile Gly Asp Thr Pro
100 105 110
Ser Leu Glu Asp Glu Ala Ala Gly His Val Thr Gln Glu Pro Glu Ser
115 120 125
Gly Lys Val Val Gln Glu Gly Phe Leu Arg Glu Pro Gly Pro Pro Gly
130 135 140
Leu Ser His Gln Leu Met Ser Gly Met Pro Gly Ala Pro Leu Leu Pro
145 150 155 160
Glu Gly Pro Arg Glu Ala Thr Arg Gln Pro Ser Gly Thr Gly Pro Glu
165 170 175
Asp Thr Glu Gly Gly Arg His Ala Pro Glu Leu Leu Lys His Gln Leu
180 185 190
Leu Gly Asp Leu His Gln Glu Gly Pro Pro Leu Lys Gly Ala Gly Gly
195 200 205
Lys Glu Arg Pro Gly Ser Lys Glu Glu Val Asp Glu Asp Arg Asp Val
210 215 220
Asp Glu Ser Ser Pro Gln Asp Ser Pro Pro Ser Lys Ala Ser Pro Ala
225 230 235 240
Gln Asp Gly Arg Pro Pro Gln Thr Ala Ala Arg Glu Ala Thr Ser Ile
245 250 255
Pro Gly Phe Pro Ala Glu Gly Ala Ile Pro Leu Pro Val Asp Phe Leu
260 265 270
Ser Lys Val Ser Thr Glu Ile Pro Ala Ser Glu Pro Asp Gly Pro Ser
275 280 285
Val Gly Arg Ala Lys Gly Gln Asp Ala Pro Leu Glu Phe Thr Phe His
290 295 300
Val Glu Ile Thr Pro Asn Val Gln Lys Glu Gln Ala His Ser Glu Glu
305 310 315 320
His Leu Gly Arg Ala Ala Phe Pro Gly Ala Pro Gly Glu Gly Pro Glu
325 330 335
Ala Arg Gly Pro Ser Leu Gly Glu Asp Thr Lys Glu Ala Asp Leu Pro
340 345 350
Glu Pro Ser Glu Lys Gln Pro Ala Ala Ala Pro Arg Gly Lys Pro Val
355 360 365
Ser Arg Val Pro Gln Leu Lys Ala Arg Met Val Ser Lys Ser Lys Asp
370 375 380
Gly Thr Gly Ser Asp Asp Lys Lys Ala Lys Thr Ser Thr Arg Ser Ser
385 390 395 400
Ala Lys Thr Leu Lys Asn Arg Pro Cys Leu Ser Pro Lys His Pro Thr
405 410 415
Pro Gly Ser Ser Asp Pro Leu Ile Gln Pro Ser Ser Pro Ala Val Cys
420 425 430
Pro Glu Pro Pro Ser Ser Pro Lys His Val Ser Ser Val Thr Ser Arg
435 440 445
Thr Gly Ser Ser Gly Ala Lys Glu Met Lys Leu Lys Gly Ala Asp Gly
450 455 460
Lys Thr Lys Ile Ala Thr Pro Arg Gly Ala Ala Pro Pro Gly Gln Lys
465 470 475 480
Gly Gln Ala Asn Ala Thr Arg Ile Pro Ala Lys Thr Pro Pro Ala Pro
485 490 495
Lys Thr Pro Pro Ser Ser Ala Thr Lys Gln Val Gln Arg Arg Pro Pro
500 505 510
Pro Ala Gly Pro Arg Ser Glu Arg Gly Glu Pro Pro Lys Ser Gly Asp
515 520 525
Arg Ser Gly Tyr Ser Ser Pro Gly Ser Pro Gly Thr Pro Gly Ser Arg
530 535 540
Ser Arg Thr Pro Ser Leu Pro Thr Pro Pro Thr Arg Glu Pro Lys Lys
545 550 555 560
Val Ala Val Val Arg Thr Pro Pro Lys Ser Pro Ser Ser Ala Lys Ser
565 570 575
Arg Leu Gln Thr Ala Pro Val Pro Met Pro Asp Leu Lys Asn Val Lys
580 585 590
Ser Lys Ile Gly Ser Thr Glu Asn Leu Lys His Gln Pro Gly Gly Gly
595 600 605
Lys Val Gln Ile Ile Asn Lys Lys Leu Asp Leu Ser Asn Val Gln Ser
610 615 620
Lys Cys Gly Ser Lys Asp Asn Ile Lys His Val Pro Gly Gly Gly Ser
625 630 635 640
Val Gln Ile Val Tyr Lys Pro Val Asp Leu Ser Lys Val Thr Ser Lys
645 650 655
Cys Gly Ser Leu Gly Asn Ile His His Lys Pro Gly Gly Gly Gln Val
660 665 670
Glu Val Lys Ser Glu Lys Leu Asp Phe Lys Asp Arg Val Gln Ser Lys
675 680 685
Ile Gly Ser Leu Asp Asn Ile Thr His Val Pro Gly Gly Gly Asn Lys
690 695 700
Lys Ile Glu Thr His Lys Leu Thr Phe Arg Glu Asn Ala Lys Ala Lys
705 710 715 720
Thr Asp His Gly Ala Glu Ile Val Tyr Lys Ser Pro Val Val Ser Gly
725 730 735
Asp Thr Ser Pro Arg His Leu Ser Asn Val Ser Ser Thr Gly Ser Ile
740 745 750
Asp Met Val Asp Ser Pro Gln Leu Ala Thr Leu Ala Asp Glu Val Ser
755 760 765
Ala Ser Leu Ala Lys Gln Gly Leu
770 775
<210> 26
<211> 758
<212> PRT
<213> Veštačka sekvenca
<220>
<223> Sintetička aminokiselinska sekvenca
<400> 26
Met Ala Glu Pro Arg Gln Glu Phe Glu Val Met Glu Asp His Ala Gly
1 5 10 15
Thr Tyr Gly Leu Gly Asp Arg Lys Asp Gln Gly Gly Tyr Thr Met His
20 25 30
Gln Asp Gln Glu Gly Asp Thr Asp Ala Gly Leu Lys Glu Ser Pro Leu
35 40 45
Gln Thr Pro Thr Glu Asp Gly Ser Glu Glu Pro Gly Ser Glu Thr Ser
50 55 60
Asp Ala Lys Ser Thr Pro Thr Ala Glu Asp Val Thr Ala Pro Leu Val
65 70 75 80
Asp Glu Gly Ala Pro Gly Lys Gln Ala Ala Ala Gln Pro His Thr Glu
85 90 95
Ile Pro Glu Gly Thr Thr Ala Glu Glu Ala Gly Ile Gly Asp Thr Pro
100 105 110
Ser Leu Glu Asp Glu Ala Ala Gly His Val Thr Gln Glu Pro Glu Ser
115 120 125
Gly Lys Val Val Gln Glu Gly Phe Leu Arg Glu Pro Gly Pro Pro Gly
130 135 140
Leu Ser His Gln Leu Met Ser Gly Met Pro Gly Ala Pro Leu Leu Pro
145 150 155 160
Glu Gly Pro Arg Glu Ala Thr Arg Gln Pro Ser Gly Thr Gly Pro Glu
165 170 175
Asp Thr Glu Gly Gly Arg His Ala Pro Glu Leu Leu Lys His Gln Leu
180 185 190
Leu Gly Asp Leu His Gln Glu Gly Pro Pro Leu Lys Gly Ala Gly Gly
195 200 205
Lys Glu Arg Pro Gly Ser Lys Glu Glu Val Asp Glu Asp Arg Asp Val
210 215 220
Asp Glu Ser Ser Pro Gln Asp Ser Pro Pro Ser Lys Ala Ser Pro Ala
225 230 235 240
Gln Asp Gly Arg Pro Pro Gln Thr Ala Ala Arg Glu Ala Thr Ser Ile
245 250 255
Pro Gly Phe Pro Ala Glu Gly Ala Ile Pro Leu Pro Val Asp Phe Leu
260 265 270
Ser Lys Val Ser Thr Glu Ile Pro Ala Ser Glu Pro Asp Gly Pro Ser
275 280 285
Val Gly Arg Ala Lys Gly Gln Asp Ala Pro Leu Glu Phe Thr Phe His
290 295 300
Val Glu Ile Thr Pro Asn Val Gln Lys Glu Gln Ala His Ser Glu Glu
305 310 315 320
His Leu Gly Arg Ala Ala Phe Pro Gly Ala Pro Gly Glu Gly Pro Glu
325 330 335
Ala Arg Gly Pro Ser Leu Gly Glu Asp Thr Lys Glu Ala Asp Leu Pro
340 345 350
Glu Pro Ser Glu Lys Gln Pro Ala Ala Ala Pro Arg Gly Lys Pro Val
355 360 365
Ser Arg Val Pro Gln Leu Lys Ala Arg Met Val Ser Lys Ser Lys Asp
370 375 380
Gly Thr Gly Ser Asp Asp Lys Lys Ala Lys Thr Ser Thr Arg Ser Ser
385 390 395 400
Ala Lys Thr Leu Lys Asn Arg Pro Cys Leu Ser Pro Lys His Pro Thr
405 410 415
Pro Gly Ser Ser Asp Pro Leu Ile Gln Pro Ser Ser Pro Ala Val Cys
420 425 430
Pro Glu Pro Pro Ser Ser Pro Lys His Val Ser Ser Val Thr Ser Arg
435 440 445
Thr Gly Ser Ser Gly Ala Lys Glu Met Lys Leu Lys Gly Ala Asp Gly
450 455 460
Lys Thr Lys Ile Ala Thr Pro Arg Gly Ala Ala Pro Pro Gly Gln Lys
465 470 475 480
Gly Gln Ala Asn Ala Thr Arg Ile Pro Ala Lys Thr Pro Pro Ala Pro
485 490 495
Lys Thr Pro Pro Ser Ser Gly Glu Pro Pro Lys Ser Gly Asp Arg Ser
500 505 510
Gly Tyr Ser Ser Pro Gly Ser Pro Gly Thr Pro Gly Ser Arg Ser Arg
515 520 525
Thr Pro Ser Leu Pro Thr Pro Pro Thr Arg Glu Pro Lys Lys Val Ala
530 535 540
Val Val Arg Thr Pro Pro Lys Ser Pro Ser Ser Ala Lys Ser Arg Leu
545 550 555 560
Gln Thr Ala Pro Val Pro Met Pro Asp Leu Lys Asn Val Lys Ser Lys
565 570 575
Ile Gly Ser Thr Glu Asn Leu Lys His Gln Pro Gly Gly Gly Lys Val
580 585 590
Gln Ile Ile Asn Lys Lys Leu Asp Leu Ser Asn Val Gln Ser Lys Cys
595 600 605
Gly Ser Lys Asp Asn Ile Lys His Val Pro Gly Gly Gly Ser Val Gln
610 615 620
Ile Val Tyr Lys Pro Val Asp Leu Ser Lys Val Thr Ser Lys Cys Gly
625 630 635 640
Ser Leu Gly Asn Ile His His Lys Pro Gly Gly Gly Gln Val Glu Val
645 650 655
Lys Ser Glu Lys Leu Asp Phe Lys Asp Arg Val Gln Ser Lys Ile Gly
660 665 670
Ser Leu Asp Asn Ile Thr His Val Pro Gly Gly Gly Asn Lys Lys Ile
675 680 685
Glu Thr His Lys Leu Thr Phe Arg Glu Asn Ala Lys Ala Lys Thr Asp
690 695 700
His Gly Ala Glu Ile Val Tyr Lys Ser Pro Val Val Ser Gly Asp Thr
705 710 715 720
Ser Pro Arg His Leu Ser Asn Val Ser Ser Thr Gly Ser Ile Asp Met
725 730 735
Val Asp Ser Pro Gln Leu Ala Thr Leu Ala Asp Glu Val Ser Ala Ser
740 745 750
Leu Ala Lys Gln Gly Leu
755
<210> 27
<211> 352
<212> PRT
<213> Veštačka sekvenca
<220>
<223> Sintetička aminokiselinska sekvenca
<400> 27
Met Ala Glu Pro Arg Gln Glu Phe Glu Val Met Glu Asp His Ala Gly
1 5 10 15
Thr Tyr Gly Leu Gly Asp Arg Lys Asp Gln Gly Gly Tyr Thr Met His
20 25 30
Gln Asp Gln Glu Gly Asp Thr Asp Ala Gly Leu Lys Ala Glu Glu Ala
35 40 45
Gly Ile Gly Asp Thr Pro Ser Leu Glu Asp Glu Ala Ala Gly His Val
50 55 60
Thr Gln Ala Arg Met Val Ser Lys Ser Lys Asp Gly Thr Gly Ser Asp
65 70 75 80
Asp Lys Lys Ala Lys Gly Ala Asp Gly Lys Thr Lys Ile Ala Thr Pro
85 90 95
Arg Gly Ala Ala Pro Pro Gly Gln Lys Gly Gln Ala Asn Ala Thr Arg
100 105 110
Ile Pro Ala Lys Thr Pro Pro Ala Pro Lys Thr Pro Pro Ser Ser Gly
115 120 125
Glu Pro Pro Lys Ser Gly Asp Arg Ser Gly Tyr Ser Ser Pro Gly Ser
130 135 140
Pro Gly Thr Pro Gly Ser Arg Ser Arg Thr Pro Ser Leu Pro Thr Pro
145 150 155 160
Pro Thr Arg Glu Pro Lys Lys Val Ala Val Val Arg Thr Pro Pro Lys
165 170 175
Ser Pro Ser Ser Ala Lys Ser Arg Leu Gln Thr Ala Pro Val Pro Met
180 185 190
Pro Asp Leu Lys Asn Val Lys Ser Lys Ile Gly Ser Thr Glu Asn Leu
195 200 205
Lys His Gln Pro Gly Gly Gly Lys Val Gln Ile Val Tyr Lys Pro Val
210 215 220
Asp Leu Ser Lys Val Thr Ser Lys Cys Gly Ser Leu Gly Asn Ile His
225 230 235 240
His Lys Pro Gly Gly Gly Gln Val Glu Val Lys Ser Glu Lys Leu Asp
245 250 255
Phe Lys Asp Arg Val Gln Ser Lys Ile Gly Ser Leu Asp Asn Ile Thr
260 265 270
His Val Pro Gly Gly Gly Asn Lys Lys Ile Glu Thr His Lys Leu Thr
275 280 285
Phe Arg Glu Asn Ala Lys Ala Lys Thr Asp His Gly Ala Glu Ile Val
290 295 300
Tyr Lys Ser Pro Val Val Ser Gly Asp Thr Ser Pro Arg His Leu Ser
305 310 315 320
Asn Val Ser Ser Thr Gly Ser Ile Asp Met Val Asp Ser Pro Gln Leu
325 330 335
Ala Thr Leu Ala Asp Glu Val Ser Ala Ser Leu Ala Lys Gln Gly Leu
340 345 350
<210> 28
<211> 351
<212> DNK
<213> Veštačka sekvenca
<220>
<223> Sintetička sekvenca nukleinske kiseline
<400> 28
gaggttcatc tggtggagtc tgggggagcc ttagtgaagc ctggagggtc cctgagactc 60
tcctgtgcag cctctggatt cagtttcagt aaatatggca tgtcttgggt tcgccaggcc 120
ccaggcaagg gcctggagtg ggtcgcaacc attagtagta gtgggagtcg cacctactat 180
ccagacagtg tgaagggcag attcaccatc tccagagaca atgccaagaa caccctgtac 240
ctgcaaatga gcagtctgaa gtctgaggac acagccatgt attactgttc aattagctgg 300
gacggtgcta tggactactg gggtcaaggg acctcagtca ccgtctcctc a 351
<210> 29
<211> 351
<212> DNK
<213> Veštačka sekvenca
<220>
<223> Sintetička sekvenca nukleinske kiseline
<400> 29
gaggttcatc tggtggagtc tgggggagcc ttagtgaagc ctggagggtc cctgagactc 60
tcctgtgcag cctctggatt cagtttcagt aaatatggca tgtcttgggt tcgccaggcc 120
ccaggcaagg gcctggagtg ggtcgcaacc attagtagta gtgggagtcg cacctactat 180
ccagacagtg tgaagggcag attcaccatc tccagagaca atgccaagaa caccctgtac 240
ctgcaaatga acagtctgag agccgaggac acagccatgt attactgttc aattagctgg 300
gacggtgcta tggactactg gggtcaaggg accaccgtca ccgtctcctc a 351
<210> 30
<211> 351
<212> DNK
<213> Veštačka sekvenca
<220>
<223> Sintetička sekvenca nukleinske kiseline
<400> 30
gaggttcagc tggtggagtc tgggggagcc ttagtgaagc ctggagggtc cctgagactc 60
tcctgtgcag cctctggatt cagtttcagt aaatatggca tgtcttgggt tcgccaggcc 120
ccaggcaagg gcctggagtg ggtcgcaacc attagtagta gtgggagtcg cacctactat 180
ccagacagtg tgaagggcag attcaccatc tccagagaca atgccaagaa caccctgtac 240
ctgcaaatga acagtctgag agccgaggac acagccatgt attactgttc aattagctgg 300
gacggtgcta tggactactg gggtcaaggg accaccgtca ccgtctcctc a 351
<210> 31
<211> 351
<212> DNK
<213> Veštačka sekvenca
<220>
<223> Sintetička sekvenca nukleinske kiseline
<400> 31
gaggttcagc tggtggagtc tgggggagcc ttagtgaagc ctggagggtc cctgagactc 60
tcctgtgcag cctctggatt cagtttcagt aaatatggca tgtcttgggt tcgccaggcc 120
ccaggcaagg gcctggagtg ggtcgcaacc attagtagta gtgggagtcg cacctactat 180
ccagacagtg tgaagggcag attcaccatc tccagagaca atgccaagaa caccctgtac 240
ctgcaaatga acagtctgag agccgaggac acagccatgt attactgtgc cattagctgg 300
gacggtgcta tggactactg gggtcaaggg accaccgtca ccgtctcctc a 351
<210> 32
<211> 336
<212> DNK
<213> Veštačka sekvenca
<220>
<223> Sintetička sekvenca nukleinske kiseline
<400> 32
gatgttttga tgacccaaag cccactctcc ctgcctgtca cccttggaca gcccgcctcc 60
atctcttgca aatctagtca gagcattgta catagtaatg gaaacaccta tttagaatgg 120
tacctgcaga aaccaggcca gtctccacag ctcctggtct acaaagtttc caatcgattt 180
tctggggtcc cagacagatt cagtggcagt ggatcaggga cagatttcac actcaagatc 240
agcagagtgg aggctgagga tgtgggaact tattactgct ttcaaggctc acttgttcct 300
tgggcgttcg gtggaggcac caaggtggaa atcaaa 336
<210> 33
<211> 336
<212> DNK
<213> Veštačka sekvenca
<220>
<223> Sintetička sekvenca nukleinske kiseline
<400> 33
gatgttgtga tgacccaaag cccactctcc ctgcctgtca cccttggaca gcccgcctcc 60
atctcttgca aatctagtca gagcattgta catagtaatg gaaacaccta tttagaatgg 120
tacctgcaga aaccaggcca gtctccacag ctcctggtct acaaagtttc caatcgattt 180
tctggggtcc cagacagatt cagtggcagt ggatcaggga cagatttcac actcaagatc 240
agcagagtgg aggctgagga tgtgggaact tattactgct ttcaaggctc acttgttcct 300
tgggcgttcg gtggaggcac caaggtggaa atcaaa 336
<210> 34
<211> 336
<212> DNK
<213> Veštačka sekvenca
<220>
<223> Sintetička sekvenca nukleinske kiseline
<400> 34
gatgttgtga tgacccaaag cccactctcc ctgcctgtca cccttggaca gcccgcctcc 60
atctcttgca aatctagtca gagcattgta catagtaatg gaaacaccta tttagaatgg 120
tacctgcaga aaccaggcca gtctccacag ctcctggtct acaaagtttc caatcgattt 180
tctggggtcc cagacagatt cagtggcagt ggatcaggga cagatttcac actcaagatc 240
agcagagtgg aggctgagga tgtgggagtg tattactgct ttcaaggctc acttgttcct 300
tgggcgttcg gtggaggcac caaggtggaa atcaaa 336
<210> 35
<211> 336
<212> DNK
<213> Veštačka sekvenca
<220>
<223> Sintetička sekvenca nukleinske kiseline
<400> 35
gatgttgtga tgacccaaag cccactctcc ctgcctgtca cccttggaca gcccgcctcc 60
atctcttgca aatctagtca gagcattgta catagtaatg gaaacaccta tttagaatgg 120
tacctgcaga aaccaggcca gtctccacag ctcctgatct acaaagtttc caatcgattt 180
tctggggtcc cagacagatt cagtggcagt ggatcaggga cagatttcac actcaagatc 240
agcagagtgg aggctgagga tgtgggagtg tattactgct ttcaaggctc acttgttcct 300
tgggcgttcg gtggaggcac caaggtggaa atcaaa 336
<210> 36
<211> 117
<212> PRT
<213> Veštačka sekvenca
<220>
<223> Sintetička aminokiselinska sekvenca
<400> 36
Glu Val His Leu Val Glu Ser Gly Gly Ala Leu Val Lys Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ser Phe Ser Lys Tyr
20 25 30
Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ala Thr Ile Ser Ser Ser Gly Ser Arg Thr Tyr Tyr Pro Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Ser Ser Leu Lys Ser Glu Asp Thr Ala Met Tyr Tyr Cys
85 90 95
Ser Ile Ser Trp Asp Gly Ala Met Asp Tyr Trp Gly Gln Gly Thr Ser
100 105 110
Val Thr Val Ser Ser
115
<210> 37
<211> 117
<212> PRT
<213> Veštačka sekvenca
<220>
<223> Sintetička aminokiselinska sekvenca
<400> 37
Glu Val His Leu Val Glu Ser Gly Gly Ala Leu Val Lys Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ser Phe Ser Lys Tyr
20 25 30
Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ala Thr Ile Ser Ser Ser Gly Ser Arg Thr Tyr Tyr Pro Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Met Tyr Tyr Cys
85 90 95
Ser Ile Ser Trp Asp Gly Ala Met Asp Tyr Trp Gly Gln Gly Thr Thr
100 105 110
Val Thr Val Ser Ser
115
<210> 38
<211> 117
<212> PRT
<213> Veštačka sekvenca
<220>
<223> Sintetička aminokiselinska sekvenca
<400> 38
Glu Val Gln Leu Val Glu Ser Gly Gly Ala Leu Val Lys Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ser Phe Ser Lys Tyr
20 25 30
Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ala Thr Ile Ser Ser Ser Gly Ser Arg Thr Tyr Tyr Pro Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Met Tyr Tyr Cys
85 90 95
Ser Ile Ser Trp Asp Gly Ala Met Asp Tyr Trp Gly Gln Gly Thr Thr
100 105 110
Val Thr Val Ser Ser
115
<210> 39
<211> 117
<212> PRT
<213> Veštačka sekvenca
<220>
<223> Sintetička aminokiselinska sekvenca
<400> 39
Glu Val Gln Leu Val Glu Ser Gly Gly Ala Leu Val Lys Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ser Phe Ser Lys Tyr
20 25 30
Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ala Thr Ile Ser Ser Ser Gly Ser Arg Thr Tyr Tyr Pro Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Met Tyr Tyr Cys
85 90 95
Ala Ile Ser Trp Asp Gly Ala Met Asp Tyr Trp Gly Gln Gly Thr Thr
100 105 110
Val Thr Val Ser Ser
115
<210> 40
<211> 112
<212> PRT
<213> Veštačka sekvenca
<220>
<223> Sintetička aminokiselinska sekvenca
<400> 40
Asp Val Leu Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Ile Val His Ser
20 25 30
Asn Gly Asn Thr Tyr Leu Glu Trp Tyr Leu Gln Lys Pro Gly Gln Ser
35 40 45
Pro Gln Leu Leu Val Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Thr Tyr Tyr Cys Phe Gln Gly
85 90 95
Ser Leu Val Pro Trp Ala Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105 110
<210> 41
<211> 112
<212> PRT
<213> Veštačka sekvenca
<220>
<223> Sintetička aminokiselinska sekvenca
<400> 41
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Ile Val His Ser
20 25 30
Asn Gly Asn Thr Tyr Leu Glu Trp Tyr Leu Gln Lys Pro Gly Gln Ser
35 40 45
Pro Gln Leu Leu Val Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Thr Tyr Tyr Cys Phe Gln Gly
85 90 95
Ser Leu Val Pro Trp Ala Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105 110
<210> 42
<211> 112
<212> PRT
<213> Veštačka sekvenca
<220>
<223> Sintetička aminokiselinska sekvenca
<400> 42
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Ile Val His Ser
20 25 30
Asn Gly Asn Thr Tyr Leu Glu Trp Tyr Leu Gln Lys Pro Gly Gln Ser
35 40 45
Pro Gln Leu Leu Val Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Phe Gln Gly
85 90 95
Ser Leu Val Pro Trp Ala Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105 110
<210> 43
<211> 112
<212> PRT
<213> Veštačka sekvenca
<220>
<223> Sintetička aminokiselinska sekvenca
<400> 43
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Ile Val His Ser
20 25 30
Asn Gly Asn Thr Tyr Leu Glu Trp Tyr Leu Gln Lys Pro Gly Gln Ser
35 40 45
Pro Gln Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Phe Gln Gly
85 90 95
Ser Leu Val Pro Trp Ala Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105 110
<210> 44
<211> 171
<212> PRT
<213> Veštačka sekvenca
<220>
<223> Sintetička aminokiselinska sekvenca
<400> 44
Ala Glu Pro Arg Gln Glu Phe Glu Val Met Glu Asp His Ala Gly Thr
1 5 10 15
Tyr Gly Leu Gly Asp Arg Lys Asp Gln Gly Gly Tyr Thr Met His Gln
20 25 30
Asp Gln Glu Gly Asp Thr Asp Ala Gly Leu Lys Ala Glu Glu Ala Gly
35 40 45
Ile Gly Asp Thr Pro Ser Leu Glu Asp Glu Ala Ala Gly His Val Thr
50 55 60
Gln Ala Arg Met Val Ser Lys Ser Lys Asp Gly Thr Gly Ser Asp Asp
65 70 75 80
Lys Lys Ala Lys Gly Ala Asp Gly Lys Thr Lys Ile Ala Thr Pro Arg
85 90 95
Gly Ala Ala Pro Pro Gly Gln Lys Gly Gln Ala Asn Ala Thr Arg Ile
100 105 110
Pro Ala Lys Thr Pro Pro Ala Pro Lys Thr Pro Pro Ser Ser Gly Glu
115 120 125
Pro Pro Lys Ser Gly Asp Arg Ser Gly Tyr Ser Ser Pro Gly Ser Pro
130 135 140
Gly Thr Pro Gly Ser Arg Ser Arg Thr Pro Ser Leu Pro Thr Pro Pro
145 150 155 160
Thr Arg Glu Pro Lys Lys Val Ala Val Val Arg
165 170
<210> 45
<211> 175
<212> PRT
<213> Veštačka sekvenca
<220>
<223> Sintetička aminokiselinska sekvenca
<400> 45
Ala Glu Pro Arg Gln Glu Phe Glu Val Met Glu Asp His Ala Gly Thr
1 5 10 15
Tyr Gly Leu Gly Asp Arg Lys Asp Gln Gly Gly Tyr Thr Met His Gln
20 25 30
Asp Gln Glu Gly Asp Thr Asp Ala Gly Leu Lys Ala Glu Glu Ala Gly
35 40 45
Ile Gly Asp Thr Pro Ser Leu Glu Asp Glu Ala Ala Gly His Val Thr
50 55 60
Gln Ala Arg Met Val Ser Lys Ser Lys Asp Gly Thr Gly Ser Asp Asp
65 70 75 80
Lys Lys Ala Lys Gly Ala Asp Gly Lys Thr Lys Ile Ala Thr Pro Arg
85 90 95
Gly Ala Ala Pro Pro Gly Gln Lys Gly Gln Ala Asn Ala Thr Arg Ile
100 105 110
Pro Ala Lys Thr Pro Pro Ala Pro Lys Thr Pro Pro Ser Ser Gly Glu
115 120 125
Pro Pro Lys Ser Gly Asp Arg Ser Gly Tyr Ser Ser Pro Gly Ser Pro
130 135 140
Gly Thr Pro Gly Ser Arg Ser Arg Thr Pro Ser Leu Pro Thr Pro Pro
145 150 155 160
Thr Arg Glu Pro Lys Lys Val Ala Val Val Arg Thr Pro Pro Lys
165 170 175
<210> 46
<211> 150
<212> PRT
<213> Veštačka sekvenca
<220>
<223> Sintetička aminokiselinska sekvenca
<400> 46
Ala Glu Pro Arg Gln Glu Phe Glu Val Met Glu Asp His Ala Gly Thr
1 5 10 15
Tyr Gly Leu Gly Asp Arg Lys Asp Gln Gly Gly Tyr Thr Met His Gln
20 25 30
Asp Gln Glu Gly Asp Thr Asp Ala Gly Leu Lys Ala Glu Glu Ala Gly
35 40 45
Ile Gly Asp Thr Pro Ser Leu Glu Asp Glu Ala Ala Gly His Val Thr
50 55 60
Gln Ala Arg Met Val Ser Lys Ser Lys Asp Gly Thr Gly Ser Asp Asp
65 70 75 80
Lys Lys Ala Lys Gly Ala Asp Gly Lys Thr Lys Ile Ala Thr Pro Arg
85 90 95
Gly Ala Ala Pro Pro Gly Gln Lys Gly Gln Ala Asn Ala Thr Arg Ile
100 105 110
Pro Ala Lys Thr Pro Pro Ala Pro Lys Thr Pro Pro Ser Ser Gly Glu
115 120 125
Pro Pro Lys Ser Gly Asp Arg Ser Gly Tyr Ser Ser Pro Gly Ser Pro
130 135 140
Gly Thr Pro Gly Ser Arg
145 150
<210> 47
<211> 121
<212> PRT
<213> Veštačka sekvenca
<220>
<223> Sintetička aminokiselinska sekvenca
<400> 47
Ala Glu Pro Arg Gln Glu Phe Glu Val Met Glu Asp His Ala Gly Thr
1 5 10 15
Tyr Gly Leu Gly Asp Arg Lys Asp Gln Gly Gly Tyr Thr Met His Gln
20 25 30
Asp Gln Glu Gly Asp Thr Asp Ala Gly Leu Lys Ala Glu Glu Ala Gly
35 40 45
Ile Gly Asp Thr Pro Ser Leu Glu Asp Glu Ala Ala Gly His Val Thr
50 55 60
Gln Ala Arg Met Val Ser Lys Ser Lys Asp Gly Thr Gly Ser Asp Asp
65 70 75 80
Lys Lys Ala Lys Gly Ala Asp Gly Lys Thr Lys Ile Ala Thr Pro Arg
85 90 95
Gly Ala Ala Pro Pro Gly Gln Lys Gly Gln Ala Asn Ala Thr Arg Ile
100 105 110
Pro Ala Lys Thr Pro Pro Ala Pro Lys
115 120
<210> 48
<211> 67
<212> PRT
<213> Veštačka sekvenca
<220>
<223> Sintetička aminokiselinska sekvenca
<400> 48
Ala Glu Pro Arg Gln Glu Phe Glu Val Met Glu Asp His Ala Gly Thr
1 5 10 15
Tyr Gly Leu Gly Asp Arg Lys Asp Gln Gly Gly Tyr Thr Met His Gln
20 25 30
Asp Gln Glu Gly Asp Thr Asp Ala Gly Leu Lys Ala Glu Glu Ala Gly
35 40 45
Ile Gly Asp Thr Pro Ser Leu Glu Asp Glu Ala Ala Gly His Val Thr
50 55 60
Gln Ala Arg
65
<210> 49
<211> 12
<212> PRT
<213> Veštačka sekvenca
<220>
<223> Sintetička aminokiselinska sekvenca
<400> 49
Asp His Ala Gly Thr Tyr Gly Leu Gly Asp Arg Lys
1 5 10
<210> 50
<211> 30
<212> PRT
<213> Veštačka sekvenca
<220>
<223> Sintetička aminokiselinska sekvenca
<400> 50
Ala Gly Thr Tyr Gly Leu Gly Asp Arg Lys Asp Gln Gly Gly Tyr Thr
1 5 10 15
Met His Gln Asp Gln Glu Gly Asp Thr Asp Ala Gly Leu Lys
20 25 30
<210> 51
<211> 10
<212> PRT
<213> Veštačka sekvenca
<220>
<223> Sintetička aminokiselinska sekvenca
<400> 51
Ala Gly Thr Tyr Gly Leu Gly Asp Arg Lys
1 5 10
<210> 52
<211> 10
<212> PRT
<213> Veštačka sekvenca
<220>
<223> Sintetička aminokiselinska sekvenca
<220>
<221> RAZNOVRS_KARAKTERISTIKA
<222> (4)..(4)
<223> Aminokielina na ovom položaju je fosforilisana
<400> 52
Ala Gly Thr Tyr Gly Leu Gly Asp Arg Lys
1 5 10
<210> 53
<211> 18
<212> PRT
<213> Veštačka sekvenca
<220>
<223> Sintetička aminokiselinska sekvenca
<400> 53
Met Ala Glu Pro Arg Gln Glu Phe Glu Val Met Glu Asp His Ala Gly
1 5 10 15
Thr Tyr
<210> 54
<211> 23
<212> PRT
<213> Veštačka sekvenca
<220>
<223> Sintetička aminokiselinska sekvenca
<220>
<221> RAZNOVRS_KARAKTERISTIKA
<222> (3)..(3)
<223> X na ovom položaju je L ili V
<400> 54
Asp Val Xaa Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys
20
<210> 55
<211> 15
<212> PRT
<213> Veštačka sekvenca
<220>
<223> Sintetička aminokiselinska sekvenca
<220>
<221> RAZNOVRS_KARAKTERISTIKA
<222> (14)..(14)
<223> X na ovom položaju je V ili I
<400> 55
Trp Tyr Leu Gln Lys Pro Gly Gln Ser Pro Gln Leu Leu Xaa Tyr
1 5 10 15
<210> 56
<211> 32
<212> PRT
<213> Veštačka sekvenca
<220>
<223> Sintetička aminokiselinska sekvenca
<220>
<221> RAZNOVRS_KARAKTERISTIKA
<222> (29)..(29)
<223> X na ovom položaju je T ili V
<400> 56
Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr
1 5 10 15
Leu Lys Ile Ser Arg Val Glu Ala Glu Asp Val Gly Xaa Tyr Tyr Cys
20 25 30
<210> 57
<211> 10
<212> PRT
<213> Veštačka sekvenca
<220>
<223> Sintetička aminokiselinska sekvenca
<400> 57
Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
1 5 10
<210> 58
<211> 5
<212> PRT
<213> Veštačka sekvenca
<220>
<223> Sintetička aminokiselinska sekvenca
<400> 58
Gly Ser Gly Gly Ser
1 5
<210> 59
<211> 4
<212> PRT
<213> Veštačka sekvenca
<220>
<223> Sintetička aminokiselinska sekvenca
<400> 59
Gly Gly Gly Ser
1
<210> 60
<211> 4
<212> PRT
<213> Veštačka sekvenca
<220>
<223> Sintetička aminokiselinska sekvenca
<400> 60
Gly Gly Ser Gly
1
<210> 61
<211> 5
<212> PRT
<213> Veštačka sekvenca
<220>
<223> Sintetička aminokiselinska sekvenca
<400> 61
Gly Gly Ser Gly Gly
1 5
<210> 62
<211> 5
<212> PRT
<213> Veštačka sekvenca
<220>
<223> Sintetička aminokiselinska sekvenca
<400> 62
Gly Ser Gly Ser Gly
1 5
<210> 63
<211> 5
<212> PRT
<213> Veštačka sekvenca
<220>
<223> Sintetička aminokiselinska sekvenca
<400> 63
Gly Ser Gly Gly Gly
1 5
<210> 64
<211> 5
<212> PRT
<213> Veštačka sekvenca
<220>
<223> Sintetička aminokiselinska sekvenca
<400> 64
Gly Gly Gly Ser Gly
1 5
<210> 65
<211> 5
<212> PRT
<213> Veštačka sekvenca
<220>
<223> Sintetička aminokiselinska sekvenca
<400> 65
Gly Ser Ser Ser Gly
1 5
<210> 66
<211> 5
<212> PRT
<213> Veštačka sekvenca
<220>
<223> Sintetička aminokiselinska sekvenca
<400> 66
His His His His His
1 5
<210> 67
<211> 6
<212> PRT
<213> Veštačka sekvenca
<220>
<223> Sintetička aminokiselinska sekvenca
<400> 67
His His His His His His
1 5
<210> 68
<211> 10
<212> PRT
<213> Veštačka sekvenca
<220>
<223> Sintetička aminokiselinska sekvenca
<400> 68
Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu
1 5 10
<210> 69
<211> 8
<212> PRT
<213> Veštačka sekvenca
<220>
<223> Sintetička aminokiselinska sekvenca
<400> 69
Asp Tyr Lys Asp Asp Asp Asp Lys
1 5
<210> 70
<211> 8
<212> PRT
<213> Veštačka sekvenca
<220>
<223> Sintetička aminokiselinska sekvenca
<400> 70
Trp Ser His Pro Gln Phe Glu Lys
1 5
<210> 71
<211> 9
<212> PRT
<213> Veštačka sekvenca
<220>
<223> Sintetička aminokiselinska sekvenca
<400> 71
Tyr Pro Tyr Asp Val Pro Asp Tyr Ala
1 5
<210> 72
<211> 5
<212> PRT
<213> Veštačka sekvenca
<220>
<223> Sintetička aminokiselinska sekvenca
<400> 72
Arg Tyr Ile Arg Ser
1 5
<210> 73
<211> 4
<212> PRT
<213> Veštačka sekvenca
<220>
<223> Sintetička aminokiselinska sekvenca
<400> 73
Phe His His Thr
1
<210> 74
<211> 17
<212> PRT
<213> Veštačka sekvenca
<220>
<223> Sintetička aminokiselinska sekvenca
<400> 74
Trp Glu Ala Ala Ala Arg Glu Ala Cys Cys Arg Glu Cys Cys Ala Arg
1 5 10 15
Ala
<210> 75
<211> 19
<212> PRT
<213> Veštačka sekvenca
<220>
<223> Sintetička aminokiselinska sekvenca
<400> 75
Thr Phe Phe Tyr Gly Gly Cys Arg Gly Lys Arg Asn Asn Phe Lys Thr
1 5 10 15
Glu Glu Tyr
<210> 76
<211> 19
<212> PRT
<213> Veštačka sekvenca
<220>
<223> Sintetička aminokiselinska sekvenca
<400> 76
Thr Phe Phe Tyr Gly Gly Ser Arg Gly Lys Arg Asn Asn Phe Lys Thr
1 5 10 15
Glu Glu Tyr
<210> 77
<211> 20
<212> PRT
<213> Veštačka sekvenca
<220>
<223> Sintetička aminokiselinska sekvenca
<400> 77
Cys Thr Phe Phe Tyr Gly Gly Ser Arg Gly Lys Arg Asn Asn Phe Lys
1 5 10 15
Thr Glu Glu Tyr
20
<210> 78
<211> 20
<212> PRT
<213> Veštačka sekvenca
<220>
<223> Sintetička aminokiselinska sekvenca
<400> 78
Thr Phe Phe Tyr Gly Gly Ser Arg Gly Lys Arg Asn Asn Phe Lys Thr
1 5 10 15
Glu Glu Tyr Cys
20
<210> 79
<211> 16
<212> PRT
<213> Veštačka sekvenca
<220>
<223> Sintetička aminokiselinska sekvenca
<400> 79
Thr Phe Val Tyr Gly Gly Cys Arg Ala Lys Arg Asn Asn Phe Lys Ser
1 5 10 15
<210> 80
<211> 17
<212> PRT
<213> Veštačka sekvenca
<220>
<223> Sintetička aminokiselinska sekvenca
<400> 80
Ala Glu Pro Arg Gln Glu Phe Glu Val Met Glu Asp His Ala Gly Thr
1 5 10 15
Tyr
<210> 81
<211> 16
<212> PRT
<213> Veštačka sekvenca
<220>
<223> Sintetička aminokiselinska sekvenca
<400> 81
Glu Val Met Glu Asp His Ala Gly Thr Tyr Gly Leu Gly Asp Arg Lys
1 5 10 15
<210> 82
<211> 8
<212> PRT
<213> Veštačka sekvenca
<220>
<223> Sintetička aminokiselinska sekvenca
<400> 82
Ala Gly Thr Tyr Gly Leu Gly Asp
1 5
<210> 83
<211> 30
<212> PRT
<213> Veštačka sekvenca
<220>
<223> Sintetička aminokiselinska sekvenca
<220>
<221> RAZNOVRS_KARAKTERISTIKA
<222> (3)..(3)
<223> X na ovom položaju je H ili Q
<400> 83
Glu Val Xaa Leu Val Glu Ser Gly Gly Ala Leu Val Lys Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ser Phe Ser
20 25 30
<210> 84
<211> 14
<212> PRT
<213> Veštačka sekvenca
<220>
<223> Sintetička aminokiselinska sekvenca
<400> 84
Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala
1 5 10
<210> 85
<211> 32
<212> PRT
<213> Veštačka sekvenca
<220>
<223> Sintetička aminokiselinska sekvenca
<220>
<221> RAZNOVRS_KARAKTERISTIKA
<222> (18)..(18)
<223> X na ovom položaju je S ili N
<220>
<221> RAZNOVRS_KARAKTERISTIKA
<222> (20)..(20)
<223> X na ovom položaju je S ili L
<220>
<221> RAZNOVRS_KARAKTERISTIKA
<222> (21)..(21)
<223> X na ovom položaju je K ili R
<220>
<221> RAZNOVRS_KARAKTERISTIKA
<222> (22)..(22)
<223> X na ovom položaju je S ili A
<220>
<221> RAZNOVRS_KARAKTERISTIKA
<222> (31)..(31)
<223> X na ovom položaju je S ili A
<400> 85
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr Leu Gln
1 5 10 15
Met Xaa Ser Xaa Xaa Xaa Glu Asp Thr Ala Met Tyr Tyr Cys Xaa Ile
20 25 30
<210> 86
<211> 11
<212> PRT
<213> Veštačka sekvenca
<220>
<223> Sintetička aminokiselinska sekvenca
<220>
<221> RAZNOVRS_KARAKTERISTIKA
<222> (6)..(6)
<223> X na ovom položaju je S ili T
<400> 86
Trp Gly Gln Gly Thr Xaa Val Thr Val Ser Ser
1 5 10

Claims (22)

1. Antitelo koje se specifično vezuje za Tau, naznačeno time, što antitelo uključuje:a) varijabilni region teškog lanca koji sadrži aminokiselinsku sekvencu navedenu u SEQ ID NO:37 i varijabilni region lakog lanca koji sadrži aminokiselinsku sekvencu navedenu u SEQ ID NO:41;b) varijabilni region teškog lanca koji sadrži aminokiselinsku sekvencu navedenu u SEQ ID NO:36 i varijabilni region lakog lanca koji sadrži aminokiselinsku sekvencu navedenu u SEQ ID NO:40;c) varijabilni region teškog lanca koji sadrži aminokiselinsku sekvencu navedenu u SEQ ID NO:36 i varijabilni region lakog lanca koji sadrži aminokiselinsku sekvencu navedenu u SEQ ID NO:41;d) varijabilni region teškog lanca koji sadrži aminokiselinsku sekvencu navedenu u SEQ ID NO:36 i varijabilni region lakog lanca koji sadrži aminokiselinsku sekvencu navedenu u SEQ ID NO:42;e) varijabilni region teškog lanca koji sadrži aminokiselinsku sekvencu navedenu u SEQ ID NO:36 i varijabilni region lakog lanca koji sadrži aminokiselinsku sekvencu navedenu u SEQ ID NO:43;f) varijabilni region teškog lanca koji sadrži aminokiselinsku sekvencu navedenu u SEQ ID NO:37 i varijabilni region lakog lanca koji sadrži aminokiselinsku sekvencu navedenu u SEQ ID NO:40;g) varijabilni region teškog lanca koji sadrži aminokiselinsku sekvencu navedenu u SEQ ID NO:37 i varijabilni region lakog lanca koji sadrži aminokiselinsku sekvencu navedenu u SEQ ID NO:42;h) varijabilni region teškog lanca koji sadrži aminokiselinsku sekvencu navedenu u SEQ ID NO:37 i varijabilni region lakog lanca koji sadrži aminokiselinsku sekvencu navedenu u SEQ ID NO:43;i) varijabilni region teškog lanca koji sadrži aminokiselinsku sekvencu navedenu u SEQ ID NO:38 i varijabilni region lakog lanca koji sadrži aminokiselinsku sekvencu navedenu u SEQ ID NO:40;j) varijabilni region teškog lanca koji sadrži aminokiselinsku sekvencu navedenu u SEQ ID NO:38 i varijabilni region lakog lanca koji sadrži aminokiselinsku sekvencu navedenu u SEQ ID NO:41;k) varijabilni region teškog lanca koji sadrži aminokiselinsku sekvencu navedenu u SEQ ID NO:38 i varijabilni region lakog lanca koji sadrži aminokiselinsku sekvencu navedenu u SEQ ID NO:42;l) varijabilni region teškog lanca koji sadrži aminokiselinsku sekvencu navedenu u SEQ ID NO:38 i varijabilni region lakog lanca koji sadrži aminokiselinsku sekvencu navedenu u SEQ ID NO:43;m) varijabilni region teškog lanca koji sadrži aminokiselinsku sekvencu navedenu u SEQ ID NO:39 i varijabilni region lakog lanca koji sadrži aminokiselinsku sekvencu navedenu u SEQ ID NO:40;n) varijabilni region teškog lanca koji sadrži aminokiselinsku sekvencu navedenu u SEQ ID NO:39 i varijabilni region lakog lanca koji sadrži aminokiselinsku sekvencu navedenu u SEQ ID NO:41;o) varijabilni region teškog lanca koji sadrži aminokiselinsku sekvencu navedenu u SEQ ID NO:39 i varijabilni region lakog lanca koji sadrži aminokiselinsku sekvencu navedenu u SEQ ID NO:42; ilip) varijabilni region teškog lanca koji sadrži aminokiselinsku sekvencu navedenu u SEQ ID NO:39 i varijabilni region lakog lanca koji sadrži aminokiselinsku sekvencu navedenu u SEQ ID NO:43.
2. Antitelo iz patentnog zahteva 1, naznačeno time, što antitelo uključuje varijabilni region teškog lanca koji sadrži aminokiselinsku sekvencu navedenu u SEQ ID NO:37 i varijabilni region lakog lanca koji sadrži aminokiselinsku sekvencu navedenu u SEQ ID NO:41.
3. Antitelo iz patentnog zahteva 1 ili 2, naznačeno time, što antitelo uključuje konstantni region teškog lanca izotipa IgG1, IgG2, IgG3, ili IgG4.
4. Antitelo iz patentnog zahteva 1 ili 2, naznačeno time, što antitelo uključuje teški lanac koji sadrži varijabilni region teškog lanca i konstantni region humanog IgG4 teškog lanca.
5. Antitelo iz patentnog zahteva 1 ili 2, naznačeno time, što antitelo uključuje teški lanac koji sadrži varijabilni region teškog lanca i konstantni region humanog IgG4 teškog lanca, pri čemu teški lanac uključuje region zgloba koji sadrži supstituciju S241P (Kabatovo numerisanje).
6. Antitelo iz patentnog zahteva 1 ili 2, naznačeno time, što antitelo uključuje (i) teški lanac koji uključuje varijabilni region teškog lanca i konstantni region humanog IgG4 teškog lanca, i (ii) laki lanac koji uključuje varijabilni region lakog lanca i konstantni region humanog kapa lakog lanca.
7. Antitelo iz patentnog zahteva 1 ili 2, naznačeno time, što antitelo uključuje (i) teški lanac koji uključuje varijabilni region teškog lanca i konstantni region humanog IgG4 teškog lanca, pri čemu teški lanac uključuje zglobni region koji sadrži supstituciju S241P (numerisanje po Kabatu), i (ii) laki lanac koji uključuje varijabilni region lakog lanca i konstantni region humanog kapa lakog lanca.
8. Antitelo iz patentnog zahteva 1 ili 2, naznačeno time, što je antitelo Fv, scFv, Fab, F(ab')2, ili Fab'.
9. Antitelo iz bilo kojeg od prethodnih patentnih zahteva, naznačeno time, što antitelo uključuje kovalentno vezani nepeptidni sintetski polimer.
10. Antitelo iz patentnog zahteva 9, naznačeno time, što je sintetski polimer poli(etilen glikol) polimer.
11. Antitelo iz bilo kojeg od prethodnih patentnih zahteva, naznačeno time, što je antitelo fuzionisano, direktno ili preko linkera, sa nosačkim molekulom, peptidom ili proteinom koji pokreće prolazak kroz krvno-moždanu barijeru.
12. Farmaceutska kompozicija, naznačena time, što uključuje: a) antitelo iz bilo kojeg od patentnih zahteva 1 do 11; ib) farmaceutski prihvatljivi ekscipijent.
13. Farmaceutska kompozicija iz patentnog zahteva 12, naznačena time, što je antitelo inkapsulirano u lipozom.
14. Farmaceutska kompozicija iz patentnog zahteva 12 ili 13,naznačenotime, što je antitelo formulisano sa sredstvom koje olakšava prolazak kroz krvno-moždanu barijeru.
15. Rekombinantni ekspresioni vektor, naznačen time, što uključuje nukleotidnu sekvencu koja kodira antitelo iz bilo kojeg od patentnih zahteva 1 do 11, pri čemu je nukleotidna sekvenca operabilno povezana sa transkripcionim kontrolnim elementom koji je aktivan u eukariotskoj ćeliji.
16. In vitro ćelija-domaćin, naznačena time, što je genetički modifikovana rekombinantnim ekspresionim vektorom iz patentnog zahteva 15.
17. Antitelo iz bilo kojeg od patentnih zahteva 1 do 11, ili farmaceutska kompozicija iz bilo kojeg od patentnih zahteva 12 do 14, za upotrebu u lečenju tauopatije kod humanog subjekta.
18. Antitelo ili farmaceutska kompozicija za upotrebu iz patentnog zahteva 17, naznačena time, što je tauopatija progresivna supranuklearna palsija.
19. Antitelo ili farmaceutska kompozicija za upotrebu iz patentnog zahteva 17, naznačena time, što je tauopatija frontotemporalna demencija.
20. Antitelo ili farmaceutska kompozicija za upotrebu iz patentnog zahteva 17, naznačena time, što je tauopatija Alzheimerova bolest.
21. Metod praćenja tauopatije kod humanog subjekta, naznačen time, što uključuje: a) određivanje prvog nivoa Tau polipeptida u biološkom uzorku dobijenom od humanog subjekta u prvoj vremenskoj tački;b) određivanje drugog nivoa Tau polipeptida u biološkom uzorku dobijenom od humanog subjekta u u drugoj vremenskoj tački; ic) upoređivanje drugog nivoa Tau sa prvim nivoom Tau, pri čemu pomenuto određivanje uključuje: i) dovođenje u kontakt biološkog uzorka sa antitelom iz bilo kojeg od patentnih zahteva 1 do 11; iii) kvantifikovanje vezivanja antitela za Tau polipeptid prisutan u uzorku.
22. Antitelo iz bilo kojeg od patentnih zahteva 1 do 11 za upotrebu u metodu detektovanja Tau polipeptida u živom humanom subjektu kod kojeg je antitelo primenjeno, pri čemu pomenuti metod uključuje detektovanje vezivanja antitela za Tau polipeptid u moždanom tkivu živog humanog subjekta, korišćenjem metoda dobijanja slike.
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