DK2646552T3 - Muteiner af human lipocalin 2 med affinitet til ctla-4 - Google Patents

Muteiner af human lipocalin 2 med affinitet til ctla-4 Download PDF

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DK2646552T3
DK2646552T3 DK11802007.2T DK11802007T DK2646552T3 DK 2646552 T3 DK2646552 T3 DK 2646552T3 DK 11802007 T DK11802007 T DK 11802007T DK 2646552 T3 DK2646552 T3 DK 2646552T3
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mutein
ser
ctla
asp
arg
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DK11802007.2T
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Gabriele Matschiner
Arne Skerra
Andreas Hohlbaum
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Pieris Pharmaceuticals Gmbh
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    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/10—Cells modified by introduction of foreign genetic material
    • 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
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
    • G01N33/57407—Specifically defined cancers
    • 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
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
    • G01N33/57484—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites
    • G01N33/57492—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites involving compounds localized on the membrane of tumor or cancer cells
    • 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
    • G01N2333/705—Assays involving receptors, cell surface antigens or cell surface determinants
    • G01N2333/70503—Immunoglobulin superfamily, e.g. VCAMs, PECAM, LFA-3
    • G01N2333/70521—CD28, CD152

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Claims (15)

  1. MUTEINER AF HUMAN LIPOCALIN 2 MED AFFINITET TIL CTLA-4 Patentkrav
    1. Lipocalinmutein, der er i stand til at binde human CTLA-4 med en affinitet med en Kd på ca. 1 nM eller lavere, hvor mutcinct omfatter mindst 9 muterede amino syrerester i aminosyresekvenspositionerne 44, 50, 79, 81, 98, 104, 125, 127, 128, 130 og/eller 134 af den lineære polypeptidsekvens af hNGAL som vist i SEQ ID NO: 20, hvor muteinet omfatter en muteret aminosyrerest i sekvensposition 44 af den lineære polypeptidsekvens af hNGAL.
  2. 2. Mutein ifølge krav 1, hvor aminosyresekvensen af muteinet omfatter et af følgende sæt af aminosyresubstitutioner: (a) Glu 44 —> Asp; Lys 50 —> Asn; Trp 79 —> Thr; Arg 81 —» Ala; Lys 125 —> Leu; Ser 127 -»· Glu; Gin 128 -»· Asp; Arg 130 Ala; Lys 134 -> Ala; (b) Glu 44 -> Asp; Lys 50 -> Asp; Trp 79 -* Pro; Arg 81 -> Ala; Thr 104 -> Trp; Lys 125 —» His; Ser 127 —> Asp; Gin 128 —> Thr; Arg 130 —> Tyr; Lys 134 —> Ser; (c) Glu 44 —> Gin; Lys 50 —> Leu; Trp 79 —* Pro; Arg 81 —> Ala; Thr 104 —* Val; Lys 125 —> His; Ser 127 —► Asp; Gin 128 —> Thr; Arg 130 —► Tyr; Lys 134 —► Ser; (d) Glu 44 —> Asp; Lys 50 —» Pro; Trp 79 —> Pro; Arg 81 —► Ala; Thr 104 —> Trp; Lys 125 —> His; Ser 127 —» Asp; Gin 128 —> Ser; Arg 130 —» Tyr; Lys 134 —> Ser; (e) Glu 44 —> Ser; Lys 50 —> Arg; Trp 79 —> Thr; Arg 81 —► Ala; Thr 104 —> Trp; Lys 125 —> His; Ser 127 —> Asp; Gin 128 —> Thr; Arg 130 —> Tyr; Lys 134 —> Ser; (f) Glu 44 —► Ser; Lys 50 Pro; Trp 79 Ser; Arg 81 —> Ala; Thr 104 —> Glu; Lys 125 —► Tyr; Gin 128 Asp; Arg 130 -^· Asp; Lys 134 —► Ser; og (g) Glu 44 —»· Leu; Lys 50 —> Pro; Trp 79 —> Pro; Arg 81 —> Ala; Lys 98 —> Arg; Lys 125 -^· His; Ser 127 —»· Asp; Gin 128 —> Thr; Arg 130 —> Tyr; Lys 134 —► Ser.
  3. 3. Lipocalinmutein ifølge et hvilket som helst af ovennævnte krav, der omfatter en aminosyresekvens valgt fra gruppen, der består af SEQ ID NO: 1 og 12-17, eller et fragment eller en variant deraf, hvilket fragment eller hvilken variant omfatter aminosyreresterne ifølge krav 1 eller 2.
  4. 4. Lipocalinmutein ifølge kravene 1 til 3, der har mindst 70 % identitet med et protein valgt fra gruppen, der består af SEQ ID NO: 1 og 12-17.
  5. 5. Mutein ifølge et hvilket som helst af kravene 1 til 4, hvor muteinet er konjugeret til en forbindelse valgt fra gruppen, der består af et organisk molekyle, et enzymmærke, et radioaktivt mærke, et farvet mærke, et fluorescerende mærke, et kromogent mærke, et luminescerende mærke, en hapten, digoxigenin, biotin, et cytostatisk middel, et toksin, et metalkompleks, et metal og kolloidt guld.
  6. 6. Mutein ifølge et hvilket som helst af kravene 1 til 5, hvor muteinet er konjugeret til en forbindelse, der forlænger muteinets halveringstid i serum, hvor forbindelsen, der forlænger halveringstiden i serum, er valgt fra gruppen, der består af et polyalkylenglycolmolekyle, hydroethylstivelse, en Fc-del af et immunoglobulin, et CH3-domæne af et immunoglobulin, et CH4-domæne af et immunoglobulin, et albuminbindende peptid og et albuminbindende protein.
  7. 7. Mutein ifølge et hvilket som helst af kravene 1 til 6 til anvendelse som en antagonist for CTLA-4.
  8. 8. Mutein ifølge et hvilket som helst af kravene 1 til 6 til anvendelse til terapi eller diagnosticering.
  9. 9. Nukleinsyremolekyle, der omfatter en nukleotidsekvens, der koder for et mutein ifølge et hvilket som helst af kravene 1 til 6.
  10. 10. Værtscelle, der indeholder et nukleinsyremolekyle ifølge krav 9.
  11. 11. Fremgangsmåde til fremstilling af et mutein ifølge et hvilket som helst af kravene 1 til 6, hvor muteinet, et fragment af muteinet eller et fusionsprotein af muteinet og et andet polypeptid dannes med udgangspunkt i nukleinsyren, der koder for muteinet, ved hjælp af gensplejsningsmetoder.
  12. 12. Farmaceutisk sammensætning, der omfatter et mutein ifølge et hvilket som helst af kravene 1 til 6 og et farmaceutisk acceptabelt excipiens.
  13. 13. Diagnostisk eller analytisk kit, der omfatter et mutein ifølge et hvilket som helst af kravene 1 til 6.
  14. 14. Farmaceutisk sammensætning, der indeholder et mutein ifølge et hvilket som helst af kravene 1 til 6 eller en farmaceutisk sammensætning ifølge krav 12 til anvendelse til behandling af cancer.
  15. 15. Fremgangsmåde til påvisning af tilstedeværelse af CTLA-4 i cn biologisk prøve, hvilken fremgangsmåde omfatter etablering af kontakt mellem prøven og et mutein ifølge et hvilket som helst af kravene 1 til 6 under betingelser, der åbner mulighed for dannelse af et kompleks mellem muteinet og CTLA-4.
DK11802007.2T 2010-12-02 2011-12-02 Muteiner af human lipocalin 2 med affinitet til ctla-4 DK2646552T3 (da)

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US41907210P 2010-12-02 2010-12-02
EP10193401 2010-12-02
PCT/EP2011/071650 WO2012072806A1 (en) 2010-12-02 2011-12-02 Muteins of human lipocalin 2 with affinity for ctla-4

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EP2646552B1 (en) 2017-07-05
US9221885B2 (en) 2015-12-29
WO2012072806A1 (en) 2012-06-07
US20140051645A1 (en) 2014-02-20
EP2646552A1 (en) 2013-10-09

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