HRP20201489T1 - Imunoglobulini konjugirani s cys80 - Google Patents
Imunoglobulini konjugirani s cys80 Download PDFInfo
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- HRP20201489T1 HRP20201489T1 HRP20201489TT HRP20201489T HRP20201489T1 HR P20201489 T1 HRP20201489 T1 HR P20201489T1 HR P20201489T T HRP20201489T T HR P20201489TT HR P20201489 T HRP20201489 T HR P20201489T HR P20201489 T1 HRP20201489 T1 HR P20201489T1
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- 108060003951 Immunoglobulin Proteins 0.000 title claims 46
- 102000018358 immunoglobulin Human genes 0.000 title claims 46
- 229940072221 immunoglobulins Drugs 0.000 title claims 3
- 235000001014 amino acid Nutrition 0.000 claims 34
- 150000001413 amino acids Chemical class 0.000 claims 27
- 150000001875 compounds Chemical class 0.000 claims 23
- 238000000034 method Methods 0.000 claims 14
- 239000003795 chemical substances by application Substances 0.000 claims 12
- NFGXHKASABOEEW-UHFFFAOYSA-N 1-methylethyl 11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate Chemical compound COC(C)(C)CCCC(C)CC=CC(C)=CC(=O)OC(C)C NFGXHKASABOEEW-UHFFFAOYSA-N 0.000 claims 9
- 235000018417 cysteine Nutrition 0.000 claims 8
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims 8
- 125000003275 alpha amino acid group Chemical group 0.000 claims 7
- 241000283973 Oryctolagus cuniculus Species 0.000 claims 6
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 claims 6
- 102000039446 nucleic acids Human genes 0.000 claims 6
- 108020004707 nucleic acids Proteins 0.000 claims 6
- 150000007523 nucleic acids Chemical class 0.000 claims 6
- 239000000427 antigen Substances 0.000 claims 5
- 102000036639 antigens Human genes 0.000 claims 5
- 108091007433 antigens Proteins 0.000 claims 5
- 125000000539 amino acid group Chemical group 0.000 claims 4
- 230000003115 biocidal effect Effects 0.000 claims 4
- 239000002738 chelating agent Substances 0.000 claims 4
- 229940079593 drug Drugs 0.000 claims 4
- 239000003814 drug Substances 0.000 claims 4
- 239000007850 fluorescent dye Substances 0.000 claims 4
- 238000011534 incubation Methods 0.000 claims 4
- 150000002632 lipids Chemical class 0.000 claims 4
- 229920001184 polypeptide Polymers 0.000 claims 4
- 102000004196 processed proteins & peptides Human genes 0.000 claims 4
- 108090000765 processed proteins & peptides Proteins 0.000 claims 4
- 150000003384 small molecules Chemical class 0.000 claims 4
- 239000000126 substance Substances 0.000 claims 4
- 102000003735 Mesothelin Human genes 0.000 claims 3
- 108090000015 Mesothelin Proteins 0.000 claims 3
- 150000003573 thiols Chemical class 0.000 claims 3
- 101100327302 Homo sapiens CD248 gene Proteins 0.000 claims 2
- 101000910338 Homo sapiens Carbonic anhydrase 9 Proteins 0.000 claims 2
- 101000576802 Homo sapiens Mesothelin Proteins 0.000 claims 2
- 230000001268 conjugating effect Effects 0.000 claims 2
- 102000051505 human CA9 Human genes 0.000 claims 2
- 239000011159 matrix material Substances 0.000 claims 2
- 230000001590 oxidative effect Effects 0.000 claims 2
- LGNCNVVZCUVPOT-FUVGGWJZSA-N (2s)-2-[[(2r,3r)-3-[(2s)-1-[(3r,4s,5s)-4-[[(2s)-2-[[(2s)-2-(dimethylamino)-3-methylbutanoyl]amino]-3-methylbutanoyl]-methylamino]-3-methoxy-5-methylheptanoyl]pyrrolidin-2-yl]-3-methoxy-2-methylpropanoyl]amino]-3-phenylpropanoic acid Chemical group CC(C)[C@H](N(C)C)C(=O)N[C@@H](C(C)C)C(=O)N(C)[C@@H]([C@@H](C)CC)[C@H](OC)CC(=O)N1CCC[C@H]1[C@H](OC)[C@@H](C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 LGNCNVVZCUVPOT-FUVGGWJZSA-N 0.000 claims 1
- 206010028980 Neoplasm Diseases 0.000 claims 1
- 201000011510 cancer Diseases 0.000 claims 1
- 238000010828 elution Methods 0.000 claims 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/40—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against enzymes
-
- 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
- A61K47/68—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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6835—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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
- A61K47/6849—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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a receptor, a cell surface antigen or a cell surface determinant
-
- 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
- A61K47/68—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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6835—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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
- A61K47/6851—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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell
-
- 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
- A61K47/68—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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6891—Pre-targeting systems involving an antibody for targeting specific cells
- A61K47/6897—Pre-targeting systems with two or three steps using antibody conjugates; Ligand-antiligand therapies
- A61K47/6898—Pre-targeting systems with two or three steps using antibody conjugates; Ligand-antiligand therapies using avidin- or biotin-conjugated antibodies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2851—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the lectin superfamily, e.g. CD23, CD72
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/44—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material not provided for elsewhere, e.g. haptens, metals, DNA, RNA, amino acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K19/00—Hybrid peptides, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes
-
- 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
- G01N33/531—Production of immunochemical test materials
- G01N33/532—Production of labelled immunochemicals
- G01N33/533—Production of labelled immunochemicals with fluorescent label
-
- 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
- A61K2039/507—Comprising a combination of two or more separate antibodies
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
-
- 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
- C07K2317/31—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
- C07K2317/50—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
-
- 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
- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
-
- 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
Claims (19)
1. Postupak dobivanja konjugiranog imunoglobulina, naznačen time što se postupak sastoji u:
skidanju kape s cisteina na aminokiselinskom položaju 80 ("Cys80") u varijabilnom području lakog lanca imunoglobulina dobivenog iz kunića, gdje se Cys80 bazira na sustavu obrojčavanja prema Kabatu ili Chothiji, gdje imunoglobulin sadrži varijabilno područje teškog lanca i varijabilno područje lakog lanca; i
konjugiranju spoja koji reagira s tiolom s Cys80, gdje spoj koji reagira s tiolom sadrži skupinu koja reagira s tiolom.
2. Postupak u skladu s patentnim zahtjevom 1, naznačen time što se skidanje kape sastoji u inkubiranju imunoglobulina s reducirajućim puferom, za čim slijedi inkubiranje imunoglobulina s oksidirajućim puferom.
3. Postupak u skladu s patentnim zahtjevom 2, naznačen time što postupak dodatno uključuje imobiliziranje imunoglobulina na matriksu prije inkubiranja s reducirajućim puferom i eluiranja imunoglobulina iz matriksa nakon inkubiranja s oksidirajućim puferom.
4. Postupak u skladu s bilo kojim od prethodnih patentnih zahtjeva, naznačen time što
(a) spoj koji reagira s tiolom je vezan na funkcionalno sredstvo, gdje funkcionalno sredstvo uključuje fluorofor, fluorescentno bojilo, polipeptid, imunoglobulin, antibiotik, nukleinsku kiselinu, radionuklid, kemijsku spojnicu, malu molekulu, kelator, lipid ili lijek, i/ili
(b) spoj koji reagira s tiolom je vezan na drugi spoj koji reagira s tiolom, gdje je drugi spoj koji reagira s tiolom vezan na drugi imunoglobulin koji ima drugo varijabilno područje teškog lanca i drugo varijabilno područje lakog lanca, gdje drugo varijabilno područje lakog lanca ima cistein na aminokiselinskom položaju 80 ("Cys802"), gdje se Cys802 bazira na sustavu obrojčavanja prema Kabatu ili Chothiji, gdje drugi spoj koji reagira s tiolom sadrži drugu skupinu koja reagira s tiolom vezanim na Cys802, i/ili
(c) Cys80 nije sparen, i/ili
(d) postupak dodatno uključuje zamjenu aminokiseline na položaju 83 aminokiselinskim ostatkom koji nije Phe, Lys ili Cys, gdje se položaj 83 bazira na sustavu obrojčavanja prema Kabatu ili Chothiji.
5. Postupak dobivanja molekule koja se veže na antigen, naznačen time što se postupak sastoji u inkubiranju prvog konjugiranog imunoglobulina s drugim konjugiranim imunoglobulinom kako bi se dobilo molekulu koja se veže na antigen, gdje:
prvi konjugirani imunoglobulin sadrži prvo varijabilno područje teškog lanca i prvo varijabilno područje lakog lanca, gdje prvo varijabilno područje lakog lanca ima cistein na položaju 80 ("Cys801"), gdje je Cys801 konjugiran s prvim spojem koji reagira s tiolom koji sadrži prvu skupinu koja reagira s tiolom, te gdje je imunoglobulin dobiven iz kunića, a Cys801 se bazira na sustavu obrojčavanja prema Kabatu ili Chothiji; i
drugi konjugirani imunoglobulin sadrži drugo varijabilno područje teškog lanca i drugo varijabilno područje lakog lanca, gdje drugo varijabilno područje lakog lanca ima cistein na položaju 80 ("Cys802"), gdje je Cys802 konjugiran s drugim spojem koji reagira s tiolom koji sadrži drugu skupinu koja reagira s tiolom, te gdje je imunoglobulin dobiven iz kunića, a Cys802 se bazira na sustavu obrojčavanja prema Kabatu ili Chothiji.
6. Postupak u skladu s patentnim zahtjevom 5, naznačen tme što
(a) Cys801, Cys802, ili oba, nije sparen, i/ili
(b) postupak dodatno uključuje, prije koraka inkubiranja,
skidanje kape s Cys801, Cys802, ili oba; i
konjugiranje prvog spoja koji reagira s tiolom s Cys801, drugog spoja koji reagira s tiolom s Cys802, ili oba, gdje prvi spoj koji reagira s tiolom sadrži prvu skupinu koja reagira s tiolom i drugi spoj koji reagira s tiolom sadrži drugu skupinu koja reagira s tiolom.
7. Postupak u skladu s bilo kojim od patentnih zahtjeva 5-6, naznačen time što
(a) prvi spoj koji reagira s tiolom dodatno sadrži prvo funkcionalno sredstvo, drugi spoj koji reagira s tiolom dodatno sadrži drugo funkcionalno sredstvo, ili oba, i/ili
(b) prvi imunoglobulin je prvi Fab, drugi imunoglobulin je drugi Fab, ili oba, i/ili
(c) postupak dodatno uključuje zamjenu aminokiseline na položaju 83 u prvom varijabilnom području lakog lanca aminokiselinskim ostatkom koji nije Phe, Lys ili Cys, zamjenu aminokiseline na položaju 83 u drugom varijabilnom području lakog lanca aminokiselinskim ostatkom koji nije Phe, Lys ili Cys, ili obje.
8. Molekula koja se veže na antigen, naznačena time što ju se proizvodi postupkom u skladu s bilo kojim od patentnih zahtjeva 5-7.
9. Imunoglobulin dobiven iz kunića naznačen time što sadrži varijabilno područje teškog lanca i varijabilno područje lakog lanca, gdje varijabilno područje lakog lanca ima cistein na položaju 80 ("Cys80"), gdje Cys80 nije sparen, i aminokiselinu koja nije Phe, Lys ili Cys na položaju 83, te gdje se Cys80 i položaj 83 baziraju na sustavu obrojčavanja prema Kabatu ili Chothiji.
10. Imunoglobulin u skladu s patentnim zahtjevom 9, naznačen time što je s Cys80 skinuta kapa.
11. Imunoglobulin u skladu s patentnim zahtjevom 9 ili 10, naznačen time što:
(A) imunoglobulin se imunospecifično veže na ljudski CA9 i sadrži:
a. varijabilno područje teškog lanca koje sadrži aminokiseline 20-141 u xil55D5HC (SEQ ID NO:52) i varijabilno područje lakog lanca koje sadrži aminokiseline 20-130 u xil55D5LC (SEQ ID NO:78);
b. varijabilno područje teškog lanca koje sadrži aminokiseline 20-144 u zul55D5HC (SEQ ID NO:54) i varijabilno područje lakog lanca koje sadrži aminokiseline 20-130 u zul55D5LC-3 (SEQ ID NO:84), zul55D5LC-4 (SEQ ID NO:86), zul55D5LC-5 (SEQ ID NO:88), zul55D5LC-6 (SEQ ID NO:90), zul55D5LC-7 (SEQ ID NO:92), zu155D5LC-huVK2-40 (SEQ ID NO:96), zu155D5LC-huVK4-1 (SEQ ID NO:100), zu155D5LChuVK6-21 (SEQ ID NO:102), zu155D5LC-huVK6D-41 (SEQ ID NO:104); ili zu155D5LC-huVK7-3-Glu8l (SEQ ID NO:106);
c. varijabilno područje teškog lanca koje sadrži aminokiseline 20-138 u xi1E4HC (SEQ ID NO:58) i varijabilno područje lakog lanca koje sadrži aminokiseline 20-130 u xi1E4LC (SEQ ID NO:110);
d. varijabilno područje teškog lanca koje sadrži aminokiseline 20-140 u zu1E4HC (SEQ ID NO:60) i varijabilno područje lakog lanca koje sadrži aminokiseline 20-130 u zu1E4LC-CXXA (SEQ ID NO:114);
e. varijabilno područje teškog lanca koje sadrži aminokiseline 20-142 u xi166B3HC (SEQ ID NO:74) i varijabilno područje lakog lanca koje sadrži aminokiseline 20-130 u xi166B3LC (SEQ ID NO:132); ili
f. varijabilno područje teškog lanca koje sadrži aminokiseline 20-145 u zu166B3HC (SEQ ID NO:76) i varijabilno područje lakog lanca koje sadrži aminokiseline 20-130 u zu166B3LC-CXXA (SEQ ID NO:136), ili
(B) imunoglobulin se imunospecifično veže na ljudski CA9 i sadrži:
a. CDR1, CDR2, te CDR3 teškog lanca u xi155D5HC, kao što je iznijeto u SEQ ID NO:146, 148, i 150, odnosno, i CDR1, CDR2, te CDR3 lakog lanca u xil55D5LC, kao što je iznijeto u SEQ ID NO:224, 226, i 228, odnosno;
b. CDR1, CDR2, te CDR3 teškog lanca u zul55D5HC, kao što je iznijeto u SEQ ID NO:152, 154, odnosno 156, i CDR1, CDR2, te CDR3 lakog lanca u zu155D5LC-3, kao što je iznijeto u SEQ ID NO:242, 244, odnosno 246, zu155D5LC-4, kao što je iznijeto u SEQ ID NO:248, 250, odnosno 252, zu155D5LC-5, kao što je iznijeto u SEQ ID NO:254, 256, odnosno 258, zu155D5LC-6, kao što je iznijeto u SEQ ID NO:260, 262, odnosno 264, zu155D5LC-7, kao što je iznijeto u SEQ ID NO:266, 268, odnosno 270, zu155D5LC-huVK2-40, kao što je iznijeto u SEQ ID NO: 278, 280, odnosno 282, zu155D5LC-huVK4-1, kao što je iznijeto u SEQ ID NO: 290, 292, odnosno 294, zu155D5LC-huVK6-21, kao što je iznijeto u SEQ ID NO: 296, 298, odnosno 300, zu155D5LC-huVK6D-41, kao što je iznijeto u SEQ ID NO: 302, 304, odnosno 306; ili zu155D5LC-huVK7-3-Glu81, kao što je iznijeto u SEQ ID NO: 308, 310, odnosno 312;
c. CDR1, CDR2, te CDR3 teškog lanca u xi1E4HC, kao što je iznijeto u SEQ ID: NO:164, 166, odnosno 168, i CDR1, CDR2, te CDR3 lakog lanca u xi1E4LC, kao što je iznijeto u SEQ ID NO:320, 322, odnosno 324;
d. CDR1, CDR2, te CDR3 teškog lanca u zu1E4HC, kao što je iznijeto u SEQ ID NO:170, 172, odnosno 174, i CDR1, CDR2, te CDR3 lakog lanca u zu1E4LC-CXXA, kao što je iznijeto u SEQ ID NO:332, 334, odnosno 336;
e. CDR1, CDR2, te CDR3 teškog lanca u xi166B3HC, kao što je iznijeto u SEQ ID NO:212, 214, odnosno 216, i CDR1, CDR2, te CDR3 lakog lanca u xil66B3LC, kao što je iznijeto u SEQ ID NO:386, 388, odnosno 390; ili
f. CDR1, CDR2, te CDR3 teškog lanca u zu166B3HC, kao što je iznijeto u SEQ ID NO:218, 220, odnosno 222, i CDR1, CDR2, te CDR3 lakog lanca u zu166B3LC-CXXA, kao što je iznijeto u SEQ ID NO:398, 400, odnosno 402, ili
(C) imunoglobulin se imunospecifično veže na ljudski TEM1 i sadrži varijabilno područje teškog lanca koje sadrži aminokiseline 20-139 u xi1-55-2HC (SEQ ID NO:56) i varijabilno područje lakog lanca koje sadrži aminokiseline 20-129 u xi1-55-2LC (SEQ ID NO:108), ili
(D) imunoglobulin se imunospecifično veže na ljudski TEM1 i sadrži CDR1, CDR2, te CDR3 teškog lanca u xi1-55-2HC, kao što je iznijeto u SEQ ID NO: 158, 160, odnosno 162, i CDR1, CDR2, te CDR3 lakog lanca u xi1-55-2LC, kao što je iznijeto u SEQ ID NO:314, 316, odnosno 318, ili
(E) imunoglobulin se imunospecifično veže na ljudski mezotelin i sadrži:
a. varijabilno područje teškog lanca koje sadrži aminokiseline 20-142 u xi33011HC (SEQ ID NO:62) i varijabilno područje lakog lanca koje sadrži aminokiseline 20-131 u xi33011LC (SEQ ID NO:116);
b. varijabilno područje teškog lanca koje sadrži aminokiseline 20-145 u zu33011HC (SEQ ID NO:64) i varijabilno područje lakog lanca koje sadrži aminokiseline 20-131 u zu33O11LC-CXXA (SEQ ID NO:120) ili zu33011LCCXXI (SEQ ID NO:122);
c. varijabilno područje teškog lanca koje sadrži aminokiseline 20-137 u xi324O5HC (SEQ ID NO:66) i varijabilno područje lakog lanca koje sadrži aminokiseline 20-127 u xi324O5LC (SEQ ID NO:124);
d. varijabilno područje teškog lanca koje sadrži aminokiseline 20-137 u xi178F16HC (SEQ ID NO:68) i varijabilno područje lakog lanca koje sadrži aminokiseline 20-127 u xi178F16LC (SEQ ID NO:126);
e. varijabilno područje teškog lanca koje sadrži aminokiseline 20-132 u xi237N18HC (SEQ ID NO:70) i varijabilno područje lakog lanca koje sadrži aminokiseline 20-127 u xi237N18LC (SEQ ID NO:128); ili
f. varijabilno područje teškog lanca koje sadrži aminokiseline 20-137 u xi383I18HC (SEQ ID NO:72) i varijabilno područje lakog lanca koje sadrži aminokiseline 20-127 u xi383I18LC (SEQ ID NO:130), ili
(F) imunoglobulin se imunospecifično veže na ljudski mezotelin i sadrži:
a. CDR1, CDR2, te CDR3 teškog lanca u xi33011HC, kao što je iznijeto u SEQ ID NO: 176, 178, odnosno 180, i CDR1, CDR2, te CDR3 lakog lanca u xi33011LC, kao što je iznijeto u SEQ ID NO:338, 340, odnosno 342;
b. CDR1, CDR2, te CDR3 teškog lanca u zu33011HC, kao što je iznijeto u SEQ ID NO:182, 184, odnosno 186, i CDR1, CDR2, te CDR3 lakog lanca u zu33O11LC-CXXA, kao što je iznijeto u SEQ ID NO:350, 352, odnosno 354, ili zu33011LC-CXXI, kao što je iznijeto u SEQ ID NO:356, 358, odnosno 360;
c. CDR1, CDR2, te CDR3 teškog lanca u xi324O5HC, kao što je iznijeto u SEQ ID NO:188, 190, odnosno 192, i CDR1, CDR2, te CDR3 lakog lanca u xi324O5LC, kao što je iznijeto u SEQ ID NO:362, 364, odnosno 366;
d. CDR1, CDR2, te CDR3 teškog lanca u xi178F16HC, kao što je iznijeto u SEQ ID NO:194, 196, odnosno 198, i CDR1, CDR2, te CDR3 lakog lanca u xi178F16LC, kao što je iznijeto u SEQ ID NO:368, 370, odnosno 372;
e. CDR1, CDR2, te CDR3 teškog lanca u xi237N18HC, kao što je iznijeto u SEQ ID NO:200, 202, odnosno 204, i CDR1, CDR2, te CDR3 lakog lanca u xi237N18LC, kao što je iznijeto u SEQ ID NO:374, 376, odnosno 378; ili
f. CDR1, CDR2, te CDR3 teškog lanca u xi383I18HC, kao što je iznijeto u SEQ ID NO:206, 208, odnosno 210, i CDR1, CDR2, te CDR3 lakog lanca u xi383I18LC, kao što je iznijeto u SEQ ID NO:380, 382, odnosno 384.
12. Konjugirani imunoglobulin, naznačen time što sadrži:
imunoglobulin u skladu s bilo kojim od patentnih zahtjeva 9-11, gdje je cistein na položaju 80 konjugiran sa spojem koji reagira s tiolom, gdje spoj koji reagira s tiolom koji sadrži skupinu koja reagira s tiolom.
13. Konjugirani imunoglobulin u skladu s patentnim zahtjevom 12, naznačen time što spoj koji reagira s tiolom dodatno sadrži funkcionalno sredstvo, gdje funkcionalno sredstvo uključuje fluorofor, fluorescentno bojilo, polipeptid, imunoglobulin, antibiotik, nukleinsku kiselinu, radionuklid, kemijsku spojnicu, malu molekulu, kelator, lipid ili lijek.
14. Konjugirani imunoglobulin protiv mezotelina namijenjen upotrebi u postupku liječenja raka kod subjekta, naznačen time što konjugirani imunoglobulin protiv mezotelina sadrži:
imunoglobulin u skladu s patentnim zahtjevom 11(E) ili 11(F), i
spoj koji reagira s tiolom koji sadrži skupinu koja reagira s tiolom, spojnicu, te funkcionalno sredstvo, gdje funkcionalno sredstvo uključuje fluorofor, fluorescentno bojilo, polipeptid, imunoglobulin, antibiotik, nukleinsku kiselinu, radionuklid, kemijsku spojnicu, malu molekulu, kelator, lipid ili lijek.
15. Konjugirani imunoglobulin protiv mezotelina namijenjen upotrebi u skladu s patentnim zahtjevom 14, naznačen time što je funkcionalno sredstvo auristatin F.
16. Molekula koja se veže na antigen, naznačena time što sadrži:
prvi konjugirani imunoglobulin, koji sadrži prvo varijabilno područje teškog lanca i prvo varijabilno područje lakog lanca, gdje prvo varijabilno područje lakog lanca ima cistein na položaju 80 ("Cys801"), gdje je Cys801 konjugiran s prvim spojem koji reagira s tiolom koji sadrži prvu skupinu koja reagira s tiolom, te gdje je imunoglobulin dobiven iz kunića, a Cys801 se bazira na sustavu obrojčavanja prema Kabatu ili Chothiji, i drugi konjugirani imunoglobulin, koji sadrži drugo varijabilno područje teškog lanca i drugo varijabilno područje lakog lanca, gdje drugo varijabilno područje lakog lanca ima cistein na položaju 80 ("Cys802"), gdje je Cys802 konjugiran s drugim spojem koji reagira s tiolom koji sadrži drugu skupinu koja reagira s tiolom, te gdje je imunoglobulin dobiven iz kunića, a Cys802 se bazira na sustavu obrojčavanja prema Kabatu ili Chothiji.
17. Molekula koja se veže na antigen u skladu s patentnim zahtjevom 16, naznačena time što
(a) Cys801, Cys802, ili oba, nije sparen, i/ili
(b) aminokiselina na položaju 83 u prvom imunoglobulinu, aminokiselina na položaju 83 u drugom imunoglobulinu, ili obje, je aminokiselinski ostatak koji nije Phe, Lys ili Cys, gdje se položaj 83 bazira na sustavu obrojčavanja prema Kabatu ili Chothiji, i/ili
(c) prvi spoj koji reagira s tiolom dodatno sadrži prvo funkcionalno sredstvo, drugi spoj koji reagira s tiolom dodatno sadrži drugo funkcionalno sredstvo, ili oba, gdje prvo i drugo funkcionalno sredstvo uključuju fluorofor, fluorescentno bojilo, polipeptid, imunoglobulin, antibiotik, nukleinsku kiselinu, radionuklid, kemijsku spojnicu, malu molekulu, kelator, lipid ili lijek, i/ili
(d) prvi imunoglobulin, drugi imunoglobulin, ili oba, je Fab.
18. Molekula nukleinske kiseline, naznačena time što kodira imunoglobulin u skladu s bilo kojim od patentnih zahtjeva 9-11.
19. Stanica domaćin, naznačena time što sadrži molekulu nukleinske kiseline u skladu s patentnim zahtjevom 18.
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US201562182020P | 2015-06-19 | 2015-06-19 | |
PCT/US2016/038041 WO2016205618A1 (en) | 2015-06-19 | 2016-06-17 | Cys80 conjugated immunoglobulins |
EP16736952.9A EP3310816B1 (en) | 2015-06-19 | 2016-06-17 | Cys80 conjugated immunoglobulins |
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US6904369B1 (en) * | 2000-06-29 | 2005-06-07 | The Trustees Of Columbia University In The City Of New York | Conjugated ligands for the stimulation of blood cell proliferation by effecting dimerization of the receptor for stem cell factor |
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