ME03539B - Multispecifični konstrukti anтitela - Google Patents

Multispecifični konstrukti anтitela

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Publication number
ME03539B
ME03539B MEP-2019-274A MEP2019274A ME03539B ME 03539 B ME03539 B ME 03539B ME P2019274 A MEP2019274 A ME P2019274A ME 03539 B ME03539 B ME 03539B
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ME
Montenegro
Prior art keywords
gly
ser
multispecific
prt
pro
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MEP-2019-274A
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German (de)
English (en)
French (fr)
Inventor
Pallavi Bhatta
Emma Dave
Sam Philip Heywood
David Paul Humphreys
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Ucb Biopharma Sprl
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Publication of ME03539B publication Critical patent/ME03539B/me

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/46—Hybrid immunoglobulins
    • C07K16/468—Immunoglobulins having two or more different antigen binding sites, e.g. multifunctional antibodies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • 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
    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/31—Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/55—Fab or Fab'
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
    • C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
    • C07K2317/622—Single chain antibody (scFv)
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
    • C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
    • C07K2317/624—Disulfide-stabilized antibody (dsFv)
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
    • C07K2317/64—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising a combination of variable region and constant region components
    • 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
    • C07K2317/94—Stability, e.g. half-life, pH, temperature or enzyme-resistance
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Medicinal Chemistry (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Engineering & Computer Science (AREA)
  • Biotechnology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Peptides Or Proteins (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicinal Preparation (AREA)

Description

LISTA SEKVENCI <br>[0297] <br>LIST SEKVENCI <br>[0297] <br>< 11 > UCB Biopharma SPRL <br>< 120> Mul tispecificni konstrukti antitela <br>< 130> G0228_ WO <br><160> 80 <br>< 170> Patentln verzija . 5 <br><210> 1 <br><211> 11 <br><212> PRT <br><213> Vestacka sekvenca <br><220> <br><223> Albumin vezujuci peptid <br><400> 1 <br>Ser Gly Gly Gly G~y Thr Gly Gly Gly Gly Ser <br>1 5 10 <br><210> 2 <br><211> 11 <br><212> PRT <br><213> Vestacka sekvenca <br><220> <br><223> Albumin vezujuci peptid <br>29 <400> 2 <br>Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser <br>l 5 10 <br><210> <br><211 > 8 <br><212> PRT <br><213> Vestacka sekvenca <br><220> <br><22?> fleksibllni veznik <br><400> ? <br><210> 4 <br><211> 11 <br><212> PRT <br>8 Lya 1'hr Bis 'l' Ala Ala <br>l 5 <br><213> Vestacka sekvenca <br><220> <br><22?> fleksibllni veznik <br><400> 4 <br>?8? Lya rhr Ri.a t'hr ??? ?.:? Pro ??? i>ro Ala <br>l 5 10 <br><210> 5 <br><211> 18 <br><212> PRT <br><21 ?> Vestacka sekvenca <br><220> <br><22?> fleksibllni veznik <br><400> 5 <br>??? t.ya rhr Bis ??.: ??? i>ro Pro ??? Pro Ala ??r ??? Pro Pro ??• <br>1 S 10 lS <br>ProAla <br><210> 6 <br><211 > 25 <br><212> PRT <br><21 ?> Vestacka sekvenca <br>30 <220> <br><223> fleksibllni veznik <br><400> 6 <br>?8? Lya Th~ Bia ?h~ ??? Pro ?~? ??? i~o Al& Th~ ??? ?~? ?~? ??? <br>1 3 10 ? <br>??? Ala !'? ??? Pro ??? ??? ??? Ala <br><210> 7 <br><211> 30 <br><212> PRT <br>~? ~5 <br><213> Vestacka sekvenca <br><220> <br><223> fleksibllni veznik <br><400> 7 <br>?8? Lya ??~ Sia ?h~ ??? ?~? ?~? ??• Pro Ala Gly I.ya Pz;o 'l'hr Leu <br>1 ! 10 13 <br>Tyr A8d ser ~ val ??t sar ??? 'fhr A.la !ily 'l'?r ??? 'ryr <br>20 25 30 <br><210> 8 <br><211> 31 <br><212> PRT <br><213> Vestacka sekvenca <br><220> <br><223> fleksibllni veznik <br><400> 8 <br>?8? I.ya 'l'h~ Bia 'l'h~ ??? Pro ?~? ??? Pz;o Al& Gly Lya ?~? 'l'h~ ?i? <br>1 ! 10 15 <br>Val A8d Val ser Val Val ??t Ala Glu val ?8? Gly '!'? ??? ??~ <br><210> 9 <br><211> 15 <br><212> PRT <br>~? 25 ?? <br><213> Vestacka sekvenca <br><220> <br>31 <22?> fleksibllni veznik <br><400> 9 <br>??? 1.?? 1'br Ri? Thr ??? ??? Val Glu ??? Pro Pro ??? Pro Ala <br>1. 5 1.0 1.5 <br><210> 10 <br><211> 26 <br><212> PRT <br><21 ?> Vestacka sekvenca <br><220> <br><22?> fleksibllni veznik <br><400> 10 <br>??? L?? 'I'?r Si.8 'rhr ??? Pro Arq ??• ?~ Glu Pro :Ly• Sez; ??• ??? <br>1 .5 10 1.5 <br>'l'hr 5'~ Pro Pro ??? ?~ ~.rq ??? Pro Al& <br>~? ~.s <br><210> 11 <br><211> 11 <br><212> PRT <br><213> Vestacka sekvenca <br><220> <br><22?> fleksibllni veznik <br><400> 11 <br>??? :t.?? 'I'?z: Ri? t?r ??? Pz:o Ser ??• Pro Ala <br>1. 5 10 <br><210> 12 <br><211 > 7 <br><212> PRT <br><21 ?> Vestacka sekvenca <br><220> <br><223> fleksibllni veznik <br><400> 12 <br>Ser Gly Gly Gly Gly Ser Glu <br>1. 5 <br>32 <210> 13 <br><211 > 6 <br><212> PRT <br><213> Vestacka sekvenca <br><220> <br><223> fleksibllni veznik <br><400> 13 <br><210> 14 <br><211 > 6 <br><212> PRT <br><213> Vestacka sekvenca <br><220> <br><223> fleksibllni veznik <br><400> 14 <br><210> 15 <br><211> 11 <br><212> PRT <br><213> Vestacka sekvenca <br><220> <br><223> fleksibllni veznik <br><400> 15 <br>??? Lya Thr ?i? Th.r Ser <br>1 5 <br>Ser Gly Gly Gly Gly Ser <br>1 5 <br>Ser Gly Gly Gly Qly Ser Gly Gly Gly Gly Ser <br>1 5 10 <br><210> 16 <br><211> 16 <br><212> PRT <br><213> Vestacka sekvenca <br>33 <220> <br><223> fleksibllni veznik <br><400> 16 <br>Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser <br>1 5 10 15 <br><210> 17 <br><211>21 <br><212> PRT <br><213> Artificial Sequence <br><220> <br><223> fleksibllni veznik <br><400> 17 <br>S.r Oly Gly Gly Oly S.r Oly Gly Gly Gly Ser Oly Gly Gly Gly Ser <br>1 ~ 10 ? <br>Gly Gly Gly Gly Ser <br>20 <br><210> 18 <br><211 > 26 <br><212> PRT <br><213> Vestacka sekvenca <br><220> <br><223> fleksibllni veznik <br><400> 18 <br>S.r Oly Gly Gly Oly S.r Oly Gly Gly Gly Ser Oly Gly Gly Gly Ser <br>1 ~ ~ ? <br>Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser <br><210> 19 <br><211> 11 <br><212> PRT <br>20 25 <br><213> Vestacka sekvenca <br><220> <br><223> fleksibllni veznik <br><400> 19 <br>34 Ala Ala Ala Gly Ser Gly Gly Ala Ser Ala Ser <br><210> 20 <br><211> 16 <br><212> PRT <br>1 5 10 <br><21 ?> Vestacka sekvenca <br><220> <br><223> fleksibllni veznik <br><220> <br><221> misc_feature <br><222> (7) .• (7) <br><223> ??? moze ?iti amino kiselina koja se prirodno javlja <br><400> 20 <br>Ala Ala Al& Oly Ser Gly ?&& Gly Gly Gly Ser Gly Ala Ser Ala Ser <br>1 5 10 15 <br><210> 21 <br><211> 21 <br><212> PRT <br><213> Vestacka sekvenca <br><220> <br><223> Fleksibllni veznik <br><220> <br><221 > misc_feature <br><222> (7) .. (7) <br><223> ??? moze ?iti amino kiselina koja se prirodno javlja <br><220> <br><221 > misc_feature <br><222> (12) .. (12) <br><223> ??? moze ?iti amino kiselina koja se prirodno javlja <br><400> 21 <br>Al& Al& Ala Cily Ser (?? ?.? Cily Cily (?? Ser ?.? Cily Gly (?? Ser <br>1 3 10 13 <br><210> 22 <br><211 > 26 <br><212> PRT <br><213> Vestacka sekvenca <br><220> <br>35 <223> Fleksibllni veznik <br><220> <br><221 > misc_feature <br><222> (7) .. (7) <br><223> ??? moze ?iti amino kiselina koja se prirodno javlja <br><220> <br><221 > misc_feature <br><222> (12) .. (12) <br><223> ??? moze ?iti amino kiselina koja se prirodno javlja <br><220> <br><221> misc_feature <br><222> (17) .. (17) <br><223> ??? moze ?iti amino kiselina koja se prirodno javlja <br><400> 22 <br>Al& Ala Ala Cilly Sel:' Gly ??? Cilly Gly Gly Sel:' ??? Cilly Gly Gly Ser <br>1 ! 10 1! <br>XU. Gly Gly Gly s.r Gly Ala S.r Ala S~ <br>20 25 <br><210> 23 <br><211> 31 <br><212> PRT <br><213> Vestacka sekvenca <br><220> <br><223> fleksibllni veznik <br><220> <br><221 > misc_feature <br><222> (7) .. (7) <br><223> ??? moze ?iti amino kiselina koja se prirodno javlja <br><220> <br><221 > misc_feature <br><222> (12) .. (12) <br><223> ??? moze ?iti amino kiselina koja se prirodno javlja <br><220> <br><221 > misc_feature <br><222> (17) .. (17) <br><223> ??? moze ?iti amino kiselina koja se prirodno javlja <br><220> <br><221 > misc_feature <br><222> (22) .. (22) <br><223> ??? moze ?iti amino kiselina koja se prirodno javlja <br><400> 23 <br>36 Ala Ala Ala Gly Se~ Gly ??? Gly aly G~y S•~ ??? Gly Gly Gly Ser <br>1 ! 10 1! <br>??& Gly Gly Gly ?? ??& Gly Gly Gly SU Gly Ala S.r Ala SU <br>20 2! ?? <br><210> 24 <br><211> 13 <br><212> PRT <br><21 ?> Vestacka sekvenca <br><220> <br><223> Fleksibllni veznik <br><220> <br><221 > misc_feature <br><222> (7) .. (7) <br><223> ??? moze ?iti amino kiselina koja se prirodno javlja <br><400> 24 <br>Ala Ala Ala Gly Ser Gly ??& Se:r: Gly Ala Ser Ala Ser <br><210> 25 <br><211> 28 <br><212> PRT <br>1 5 10 <br><213> Vestacka sekvenca <br><220> <br><223> Fleksibllni veznik <br><400> 25 <br>Pro Gly Gly A8n A.l;fJ Gly D~ D~ Th~ Thr bl'iJ AriJ ??? IU& 'l'br Thr <br>1 ! 10 Hi <br>Dr Gly S.r su Pro Gly Pro nr GJ.:I su ?1? 'l'yr <br>20 25 <br><210> 26 <br><211> 11 <br><212> PRT <br><213> Vestacka sekvenca <br><220> <br><223> Fleksibllni veznik <br><400> 26 <br>Ala 'l'hr t'hr t'hr Gly Ser Ser Pro CRy Pro 'l'hr <br>1 5 10 <br>37 <210> 27 <br><211 > 6 <br><212> PRT <br><213> Vestacka sekvenca <br><220> <br><22?> Fleksibllni veznik <br><400> 27 <br><210> 28 <br><211> 21 <br><212> PRT <br><213> Vestacka sekvenca <br><220> <br><22?> Fleksibllni veznik <br><400> 28 <br>Ala Thr Thr Thr Gly Ser <br>1 5 <br>Olu ?~? Se~ Gly ?~ %le S.~ ??~ Ile Aan S•~ ?~? ?~? Se~ Ly• Glu <br>1 5 10 1! <br>ser Bil J.yl s? l'ro <br>2D <br><210> 29 <br><211> 15 <br><212> PRT <br><21 ?> Vestacka sekvenca <br><220> <br><22?> Fleksibllni veznik <br><400> 29 <br>Gly 'l'hr Val Ala Ala Pro Se~ Val Phe :tle ??? Pro Pro Ser ??? <br>1 5 u ~ <br><210> ?? <br><211> 15 <br><212> PRT <br><21 ?> Vestacka sekvenca <br>38 <220> <br><223> Fleksibllni veznik <br><400> 30 <br>Gly Gly Gly Gly Ile Ala Pro Ser ??t val Gly Gly Gly G~y Ser <br>1 5 10 15 <br><210> 31 <br><211> 15 <br><212> PRT <br><213> Vestacka sekvenca <br><220> <br><223> Fleksibllni veznik <br><400> 31 <br>Gly Gly Gly G~y Lya Val G~u Gly Ala Gly Gly Gly Gly Gly Ser <br>1 5 10 15 <br><210> 32 <br><211> 15 <br><212> PRT <br><213> Vestacka sekvenca <br><220> <br><223> Fleksibllni veznik <br><400> 32 <br>Gly Gly Gly G~y Ser ??t L?? Ser ?i? Asp Gly Gly Gly Gly Ser <br>1 5 ~ ~ <br><210> 33 <br><211> 15 <br><212> PRT <br><213> Vestacka sekvenca <br><220> <br><223> fleksibllni veznik <br><400> 33 <br>Gly Qly Gly Gly Asn Leu Ile ?hr Ile Val Gly G . ly Gly Gly Ser <br>1 s u u <br><210> 34 <br><211> 15 <br><212> PRT <br>39 <213> Vestacka sekvenca <br><220> <br><223> Fleksibllni veznik <br><400> 34 <br>Gly G~y Gly Gly V&l Val Pro Ser Leu Pro Gly Gly Gly Gly Ser <br>1 5 10 15 <br><210> 35 <br><211> 12 <br><212> PRT <br><213> Vestacka sekvenca <br><220> <br><223> Fleksibllni veznik <br><400> 35 <br>Gly Gly Glu Lya Ser Ile Pro Gly G~y Gly Gly Ser <br>1 5 10 <br><210> 36 <br><211>18 <br><212> PRT <br><213> Vestacka sekvenca <br><220> <br><223> Fleksibllni veznik <br><400> 36 <br>?9 Pro :t.eu S.or ??r Az.-9 Pz.-o Pz.-o ??• lil'~:o ??. Gly Phe Pro S.r Val <br>1 !5 10 1!5 <br><210> 37 <br><211> 18 <br><212> PRT <br><213> Vestacka sekvenca <br><220> <br><223> Fleksibllni veznik <br><400> 37 <br>??!: Pz.-o AI."YJ S.or I? '!?1: Ile MCiJ Ar9 Ar9 Hia Poro S.1: ?1:? Ser lAu <br>1 s 10 13 <br>'l'?r ??r <br>40 <210> 38 <br><211> 18 <br><212> PRT <br><213> Vestacka sekvenca <br><220> <br><223> Fleksibllni veznik <br><400> 38 <br>t'hr Pro Ser ?i? Leu Ser Bia Ile Leu l>ro Ser ??? Gly Leu Pro i'hr <br>1 s 10 15 <br>??? Aan <br><210> 39 <br><211> 18 <br><212> PRT <br><213> Vestacka sekvenca <br><220> <br><223> Fleksibllni veznik <br><400> 39 <br>Arq Pro Va1 Ser Pro Phe 1'tu: ??? Pro Arq l.eu Ser Aan Ser 'trp Leu <br>1 5 10 15 <br><210> 40 <br><211> 18 <br><212> PRT <br><213> Vestacka sekvenca <br><220> <br><223> Fleksibllni veznik <br><400> 40 <br>Ser Pro Ala Ala ?i? Phe Pro ArCJ Ser Ile Pro ArCJ Pro Gly Pro :Ile <br>1 <br>10 <br>1S <br>41 <210> 41 <br><211> 18 <br><212> PRT <br><213> Vestacka sekvenca <br><220> <br><223> Fleksibllni veznik <br><400> 41 <br>Al& Pro Qly Pro Ser Al& Pro S.r Bia Arq Sar Leu Pro Ser Arq Al& <br>1 ! 10 1!1 <br>??? Gly <br><210> 42 <br><211> 18 <br><212> PRT <br><213> Vestacka sekvenca <br><220> <br><223> Fleksibllni veznik <br><400> 42 <br>Pro ? A.rl Ser Ile Hi.a ??. l.eu Hia Pro l.eu l.eu Val Ala Pro 1.811 <br>1 5 10 1! <br>Gly Al.a <br><210> 43 <br><211> 18 <br><212> PRT <br><213> Vestacka sekvenca <br><220> <br><223> Fleksibllni veznik <br><400> 43 <br>Nat Pro Ser l.eu Ser Gly Val Leu Gln Val Arq 'l'yx Leu S.r Pro Pro <br>1 ! 10 15 <br>??? Leu <br><210> 44 <br>42 <211> 18 <br><212> PRT <br><213> Vestacka sekvenca <br><220> <br><223> fleksibllni veznik <br><400> 44 <br>Se.r Pro Gln ??r Pro Sez Pro Leu t'?r Leu ??r Leu Pro Pro Ris Pro <br>1 5 10 lS <br><210> 45 <br><211> 18 <br><212> PRT <br><213> Vestacka sekvenca <br><220> <br><223> Fleksibllni veznik <br><400> 45 <br>Alln Pro Ser Leu Alln Pro Pro Ser ??r Leu Hia Ar!J Ala li'ro Ser Arq <br>1 5 10 15 <br><210> 46 <br><211> 17 <br><212> PRT <br><213> Vestacka sekvenca <br><220> <br><223> Fleksibllni veznik <br><400> 46 <br>Leu Pro Trp Arq Thr Ser Leu Leu li'ro Ser Leu Pro :r.eu A:rq Arq Arq <br>1 s u u <br><210> 47 <br><211> 18 <br><212> PRT <br>43 <213> Vestacka sekvenca <br><220> <br><223> Fleksibllni veznik <br><400> 47 <br>Pro Pro Leu Phe Al.a L?? G~y Pro Val Gly Leu x.eu Ser Arq Ser Phe <br><210> 48 <br><211> 18 <br><212> PRT <br>1 <br>l'ro Pro <br><213> Vestacka sekvenca <br><220> <br><223> fleksibllni veznik <br><400> 48 <br>10 <br>Val Pro Pro Ala Pro Val Val S.r Leu ? Ser Ala lli? ?? ? Pro <br>1 s 10 15 <br>Pro Tyr <br><210> 49 <br><211> 17 <br><212> PRT <br><213> Vestacka sekvenca <br><220> <br><223> Fleksibllni veznik <br><400> 49 <br>Leu Arq l'ro Thr Pro Pro Arq Val Argo Ser ???- ??r ??? Cys Pro 'l'hr <br>1 ~ 10 1! <br>l'ro <br>44 <br>1~ <210> 50 <br><211> 18 <br><212> PRT <br><213> Vestacka sekvenca <br><220> <br><223> Fleksibllni veznik <br><400> 50 <br>?~? Aan Val Al& ?~• Val Le~ ?~? Le~ Leu Th~ Val ?~? ??? ?8? A8n <br>1 ~ 10 1! <br><210> 51 <br><211> 18 <br><212> PRT <br><213> Vestacka sekvenca <br><220> <br><223> Fleksibllni veznik <br><400> 51 <br>??• Aan Pro I.eu Leu Pro :Leu ??• Ala Ar9 Ser Pro Ala Val Ar9 Thr <br>1 5 10 lS <br>??? ?~? <br><210> 52 <br><211> 11 <br><212> PRT <br><213> Vestacka sekvenca <br><220> <br><223> Cvrsti veznik <br><400> 52 <br><210> 53 <br><211 > 4 <br><212> PRT <br>Gly Ala Pro Ala Pro Ala Ala Pro Ala Pro Ala <br>1 5 10 <br>45 <213> Vestacka sekvenca <br><220> <br><223> Cvrsti veznik <br><400> 53 <br><210> 54 <br><211> 11 <br><212> PRT <br><213> Vestacka sekvenca <br><220> <br><223> Albumin vezujuci peptid <br><400> 54 <br>Pro Pro Pro Pro <br>1 <br>??? Leu ??? Leu Arq ??? frp Gly ??? Leu 'l'rp <br>l 5 10 <br><210> 55 <br><211> 11 <br><212> PRT <br><213> Vestacka sekvenca <br><220> <br><223> Al?umin vezujuci peptid <br><400> 55 <br>??? Ile ??? Leu Pro Arq 'l'rp Gly ??? Leu trp <br>l 5 10 <br><210> 56 <br><211> 15 <br><212> PRT <br><213> Vestacka sekvenca <br><220> <br><223> Albumin vezujuci peptid <br><400> 56 <br>46 ??t Glu ??? Ile ??? Leu Pro Ar9 Trp Gly ??? :Leu Trp Gly ?8? <br>1 5 10 15 <br><210> 57 <br><211> 20 <br><212> PRT <br><213> Vestacka sekvenca <br><220> <br><223> Albumin vezujuci peptid <br><400> 57 <br>Gln Ar9 L8u Net Qlu ?8? 11• ??? Leu Pr:-o ? 'frp Gly ??? Leu 'l'rp <br>1 5 10 1! <br>Glu ??? Up Glu <br>20 <br><210> 58 <br><211 > 20 <br><212> PRT <br><213> Vestacka sekvenca <br><220> <br><223> Albumin vezujuci peptid <br><400> 58 <br>Gln Qly L8u tle Qly ?8? lle ??? ?.- P;r;o ? 'frp Gly ??? Leu 'l'rp <br>1 5 10 1! <br>Gly Acq Ser Val. <br>20 <br><210> 59 <br><211> 21 <br><212> PRT <br><213> Vestacka sekvenca <br><220> <br><223> AI?umin vezujuci peptid <br><400> 59 <br>Gln Gly L8u tle Qly ?8? lle ??• L4N P;r;o ? 'frp CJly ??? Leu 'l'rp <br>1 5 10 1! <br>Gly ~ S•r Val Ly• <br>20 <210> 60 <br><211> 15 <br><212> PRT <br><213> Vestacka sekvenca <br><220> <br><22?> Albumin vezujuci peptid <br><400> 60 <br>Glu ??? Ile ??? Leu Pro ?rq Trp Gly ??? Leu Trp Glu ??? .IUip <br>1 5 10 15 <br><210> 61 <br><211>18 <br><212> PRT <br><21 ?> Vestacka sekvenca <br><220> <br><22?> Albumin vezujuci peptid <br><400> 61 <br>Al:'q Leu *t Glu Alp :tle ??? :Leu ??;? ? ??;? Gly ??• J.tN ??? Qlu <br>1 3 10 13 <br><210> 62 <br><211> 16 <br><212> PRT <br><21 ?> Vestacka sekvenca <br><220> <br><22?> Albumin vezujuci peptid <br><400> 62 <br>Jfet Glu .1U1p Ile ??? Leu Pro Arq Trp Gly Cys Leu Trp Glu ??? .IUip <br>1 5 u u <br>48 <210> 63 <br><211> 15 <br><212> PRT <br><213> Vestacka sekvenca <br><220> <br><223> A!?umin vezujuci peptid <br><400> 63 <br>.Net Glu ?8? Ile ??? Leu Pro Ar9 Trp Gly ??• Leu Trp Glu ??? <br>1 5 10 lS <br><210> 64 <br><211> 18 <br><212> PRT <br><213> Vestacka sekvenca <br><220> <br><223> Albumin vezujuCi peptid <br><400> 64 <br>~~~~-~~~~~~~~~~~ <br>1 5 10 15 <br>?8? ??? <br><210> 65 <br><211> 20 <br><212> PRT <br><213> Vestacka sekvenca <br><220> <br><223> Albumin vezujuCi peptid <br><400> 65 <br>Qlu V&l ? Ser .Phe ??• 'l'hz:-~ ,.rp .Pz:-o ??.? Glu :t.y• Sez:- ??• ?.?• <br>1 ~ 10 1~ <br>Pro ~ ~ Gly <br>20 <br><210> 66 <br><211> 20 <br><212> PRT <br><213> Vestacka sekvenca <br>49 <220> <br><223> Albumin vezujuCi peptid <br><400> 66 <br>k9 Ala t~o Qlu Se~ t?. V&l ??• ??~ 'l"Ep Glu 'l'h~ lle ??? t?. Qlu <br>1 ! 10 1! <br>Arg Se~ Glu Gln <br>.?? <br><210> 67 <br><211> 11 <br><212> PRT <br><21 ?> Vestacka sekvenca <br><220> <br><223> Albumin vezujuci peptid <br><400> 67 <br>Glu Net ??? Tyr Phe Pro Gly Ile ??? t'rp Net <br>?. 5 ?.? <br><210> 68 <br><211> 20 <br><212> PRT <br><213> Vestacka sekvenca <br><220> <br><223> Albumin vezujuci peptid <br><400> 68 <br>Qly Qly Oly Oly Se~ Qly Qly Oly Gly Se~ Qly Qly Gly Gly Se~ Qly <br>1 ! ~ ~ <br>Gly Gly Gly Ser <br>20 <br><210> 69 <br><211> 16 <br><212> PRT <br><213> Vestacka sekvenca <br><220> <br><223> fleksibllni veznik <br>50 <400> 69 <br>Ser Gly Gly Gly Gly Ser Gly G1y Gly Gly Ser G1y Gly Gly Gly Ser <br>1 5 ~ u <br><210> 70 <br><211> 16 <br><212> PRT <br><213> Vestacka sekvenca <br><220> <br><223> fleksibllni veznik <br><400> 70 <br>Ser Gly G1y Gly Gly Ser Gly G1y Gly Gly Thr Gly G1y G~y G~y Ser <br>1 5 10 15 <br><210> 71 <br><211>10 <br><212> PRT <br><213 > Vestacko <br><220> <br><223> CDRH1 dAbH1 <br><400> 71 <br><210> 72 <br><211> 16 <br><212> PRT <br><213> vestacko <br><220> <br>Gly Ile Allp I.eu Ser Asn 'ryr Ala I.le ??n <br>1 5 10 <br><223> CDRH2 dAbH1 <br><400> 72 <br>Ile Ile Trp Ala Ser Gly 'fhr 'fhr Phe 'ryr Ala 'fhr t'rp Ala Lya Gly <br>1 s 10 15 <br><210> 73 <br>51 <211> 13 <br><212> PRT <br><213> Vestacko <br><220> <br><223> ?DR?? dAbH1 <br><400> 73 <br>?hr Val l>ro Gly 'fyr Ser Thr Ala Pro Tyr l'he ??? Leu <br>1 5 10 <br><210> 74 <br><211> 12 <br><212> PRT <br><213> Vestacko <br><220> <br><223> CDRL 1 d?? 1 <br><400> 74 <br>Gln Ser Ser l'ro Ser va.l Trp Ser Alm ??? Leu Ser <br>1 5 10 <br><210> 75 <br><211 > 7 <br><212> PRT <br><213> Artificial <br><220> <br><223> CDRL2 d?? 1 <br><400> 75 <br><210> 76 <br><211> 11 <br><212> PRT <br><213> Artificial <br>Glu Ala Ser Lya :teu Thr Ser <br>1 5 <br>52 <220> <br><223> CDRL? d?? 1 <br><400> 76 <br>Gly Gly Gly tyr Ser Ser Ile Ser ??? thr ~hr <br>?. s 10 <br><210> 77 <br><211> 121 <br><212> PRT <br><21 ?> Artificial <br><220> <br><223> Varijabllni domen teskog lanca anti Albumin antitela (nema ds) <br><400> 77 <br>Glu V.l Qln 1.tn1 Leu Qlu Se:r- Cilly Gly Gly Leu Val Cilln Pro Gly tily <br>1 ' ~ ~ <br>ser IAu Arq t.ev ser Cyt Ala va1 Ser G.ly Ile ?? t.?? s.r Atn ??:? <br>20 :2!1 30 <br>Ala tle ??n !'rp Val Arq Gln .Ua l'ro Gly l.ys Gly t.eu Glu txp Ile <br>?s •? •s <br>Gly :tle J:le 'l'rp Ala Ser Gly 'l'hr 'l'hr Phe Tyr Ala 'l'hr '!'rp ??. Ly4 <br>so 55 60 <br>Gly Arq ??? ?hr Ile Ser Arq ??? Aan Se.r l.ys Asn t'hr Val tyr Leu <br>6S 10 15 80 <br>G.ln ??t A8n S.r Leu Arq Ala Glu ?8? ??r Ala Val ??r ??r CYI Ala <br>85 90 95 <br>-~~~~~~~~~~~-~txp~ <br>100 10!1 110 <br>Gln Gly '!'?r Leu Val ?~ Val S.r Ser <br><210> 78 <br><211> 121 <br>115 120 <br>53 <212> PRT <br><213> Artificial <br><220> <br><223> Varijabllni domen teskog lanca anti Al?umin antetela (nema ds) <br><400> 78 <br>Gl11 Val Cilln Leu Leu Glu Sa:r Gly Gly Gly Leu Val Cilln :Pro Gly Cilly <br>1 3 ? ~ <br>Se.r Leu Arq Leu Se.r ??? Ala Val Ser Gly Ile Alrp Le'\1 Ser Aan 'l'yr <br>20 25 30 <br>Ala Ile Aan 'rrp V&l. A:rg Cilln ?1.? Pro Gly Lya ??? 1.811 1311.1 '1':rp Ile <br>35 40 45 <br>Gly tle 1le 'rrp Ala Se.r Gly Thr ?'?r Phe Ty:r Ala 'rhr 'trp Ala Lya <br>50 55 '? <br>G.ly Arq Pha 'l'hr Ile Se.r Arq A1rp Aan se.r Lya Aan 'l'hr Val ??r Leu <br>65 70 75 80 <br>Gln ?.t; .?? Ser loe!~ A:rg .U.a Qlu ??? ?hr Ala V.l 'tyr ??r ??? Ala <br>85 90 95 <br>ArcJ 'l'h.r val Pro Gly ??r se.r Thr Ala P.ro ??r Phe .up Leu ??:? Gly <br>100 105 110 <br><nn gly="" ??r="" leu="" val="" th.r="" va.l="" ser="" <br=""></nn>115 120 <br><210> 79 <br><211> 112 <br><212> PRT <br><213> Artificial <br><220> <br><223> Varijabllni domen lakog lanca anti Albumin antitela (nema ds) <br>54 <400> 79 <br>??? Ile Oln ?.t ?h~ Gln Se~ ?~? S.~ &?~ VaJ. Se~ Ala S.~ V&l Oly <br>1 .5 10 1.5 <br>??? Arg val 'I'?r Ile ??r ??? Gln S.r Sar Pro Ser Val 'l'rp Sar Aan <br>20 2$ ?? <br>??. :IAu Ser 'l'q:. ?t~: Gln Ciln Z.ya ?~? Gly Lya Ala ?~? loya Z..u :IAu <br>?s •? •s <br>lle ?t~ Glu Ala ??~ Lya J.e-g "rh~ ?? Gly V&l ?~? Se~ ? ??? Ser <br>50 55 60 <br>Gly ser Gly Sar Gly !'?r ?8? ??. ??.r :t..u fhr Ile Ser 8ar z..u Gln <br>65 70 75 80 <br>Pro Glu ??? Phe Al& 1'hr 'tyr 'tyr ??? Gly Gly Gly 'fyr Ser Ser Ile <br>85 90 95 <br>S.r ?8? 'rl\r '1'hr 1'?. Gly Gly Gly ??r Lya Val Glu Ile Lya ArQ !'hr <br>100 105 110 <br><210> 80 <br><211> 112 <br><212> PRT <br><213> Artificial <br><220> <br><223> Varijabllni domen lakog lanca anti Albumin antitela (nema ds) <br><400> 80 <br>55 ?8? Ile Gln ??t 'rhE' Gln Sez; Pz;o Sez: Sez: Val Sez; Ala Sez; Val Qly <br>1 3 10 13 <br>Up Arq val ?hr J:le ??r ??8 Gl.n Ser Ser Pro Ser val. '!'rp Ser Un <br>20 25 30 <br>Phe Leu. Se:~r ~ql '?r~r G1n Gln 1.?• P~ro Gly Ly• Ala P~ro Ly• Leu Leu. <br>?s •? •s <br>Il.e l'y:r Glu Al.a ser Lyl Leu 'l'?r Ser Gly Val Pro Ser Ar9 ??? Se:r <br>!? !5 60 <br>~~~~~??r~~~~~~~~~~ <br>6!1 70 7!1 80 <br>P:ro Glu ?8? ??. Ala ??r Ty:r 'l'yr ??8 Gly Gly Gly 'l'yr Ser Ser Ile <br>85 90 95 <br>S~ UP 'l'?r 'fhr ??. Gly ??• Gly 'fhr Ly• Val Glu Ile Lyl At'q Thr <br>100 10!1 110 <br>56

Claims (24)

1. Multispeclfični moleku!antltela obuhvatajući ili sastojeći se od: a) polipeptidnog lanca formule (1): ib) polipeptidnog lanca formule (ll): pri čemu: VH predstavlja varijabilni domen teškog lanca;CH, predstavlja domen konstantnog regiona teškog lanca, na primer, domen 1 istog; X predstavlja vezu lli veznik;Y predstavlja vezu ili veznik;v, predstavlja dsFv ili dsscFv;VL predstavlja varijabilni domen lakog lanca;Ct predstavlja domen iz konstantnog regiona lakog lanca, kao što je Ckappa;Vz predstavlja dsFv ili dsscFv.
2.Multlspeciflčni moleku!antitela prema patentnom zahtevu 1, pri čemu je X veznik.
3.Multispecifični moleku!antitela prema bilo kojem od patentnih zahteva od 1 do 2, pri čemu je Y veznik.
4.Multispeciflčni moleku!antitela prema bilo kojem od patentnih zahteva od 1 do 3, pri čemu v, je dsFv, i Vz je dsFv. S.
5. Multispeclflčnl moleku! antitela prema bilo kojem od patentnih zahteva od 1 do 3, pri čemu v, je dsscFv i Vz je dsscFv.
6.Multispecifičnl moleku! antitela prema bilo kojem od patentnih zahteva od 1 do 3, pri čemu v, je dsscFv i Vz je dsFv, ili pri čemu v, je dsFv, l Vz je dsscFv.
7.Multispecifični moleku! antitela prema bilo kojem od patentnih zahteva od 1 do 6, pri čemu je varijabilni domen lakog lanca ili varijabilni domen teškog lanca od v, spojen na X, na primer, putem peptldne veze.
8.Multtspeciflčnl moleku! antitela prema bilo kojem od patentnih zahteva od 1 do 7, pri čemu je varijabilni domen lakog lanca ili varijabilni domen teškog lanca od Vz spojen naY, na primer, putem pepttdne veze.
9. Multispecifičnimoleku! antttela prema bilo kojem od patentnih zahteva od 1 do 8, prt čemu su vartjabtlnt domeni lakog lanca iteškog lanca od v1 i/ili varijabilnidomene lakog lanca i teškog lanca od v2 povezaniputem disulfidne vezeizmeđu dva konstruisana ostatka cisteina. 59
10. Multispecifični moleku!antttela prema bilo kojem od patentnih zahteva od 1 do 9,pričemu su varijabilnidomeni teškog lanca i lakog lanca od v1 i/ili v2 povezani putem dtsulfidne veze između dva ostatka cisteina, prt čemu jepozicija para cisteinskih ostataka izabrana iz grupe obuhvatajući ili sastojeći se od : VH37 l VL95, VH44 t VL100, VH44 i VL105, VtAS l VL87, VH100 i VL50, VH100b j VL49, VH98 i VL46, VH101 i VL46, VH105 j VL43 j VH106 i VL57 (numertsanje prema Kabatu), prt čemu su vrednosti VH iVL nezavisno izabrane unutar datog v1 ili v2.
11. Multispecifični molekul antitela prema patentnom zahtevu 1O, prt čemu je pozicija para konstruisanlh ostataka cisteina VH44 iVL100.
12. Multispecifičnimoleku!antitela prema bilo kojem od patentnih zahteva od 1 do 11,pričemu je X pepttdnt veznik.
13. Multispectfičnimoleku!antitela prema patentnom zahtevu 12, prt čemu je X peptidniveznik izabran od SEK ID BR:1, 2, 69 i70.
14. Multispecifičnimoleku!antltela prema btlo kojem od patentnih zahteva 1 do13, prt čemu je Y peptidnt veznik.
15. Multispecifičnt moleku! antjtela prema patentnom zahtevu 14,prt čemu je Y peptidni veznik izabran od SEK ID BR:1, 2, 69 j 70.
16. Multispecifičnimoleku!antitela prema bilo kojem od patentnih zahteva 1 do 15, koji je tri-specifičan.
17. Tri-specifičnimoleku! antitela prema patentnom zahtevu 16, prt čemu svakiod trt vezujućih domena veže različite antigene.
18. Polinukleotid kojikodira multispecifičnimoleku!antitela prema bilo kojem od patentnih zahteva od 1 do 17.
19. Vektor kojiobuhvata polinukleotid definisan u patentnom zahtevu 18.
20. Ćelija domaćina koja obuhvata polinukleotid ili vektor iz patentnog zahteva 18 ili 19 respektivno.
21. Ćelija domaćina koja obuhvata dva lli trt vektora, svaki vektor obuhvata poltnukleottd koji kodira različiti lanac polipeptlda multispectftčnog molekula antitela prema bilo kojem od patentnih zahteva od 1 do 17.
22. Postupak koji obuhvata ekspresiju multispecifičnog molekula antitela tz ćelije domaćina deftnisanu u patentnom zahtevu 20 ill patentnom zahtevu 21.
23. Farmaceutska kompozicija, koja obuhvata multispectftčnimoleku!antitela prema bilo kojem od patentnih zahteva od 1 do 17 inajmanje jedan ekscipljent.
24. MulUspeclfični molekul antitela prema bilo kojem od patentnih zahteva od 1 do 17 lli farmaceutska kompozicija prema patentnom zahtevu 23,za upotrebu u tretmanu.
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