HRP20210410T1 - Konjugirana antitijela prema ly75 za liječenje raka - Google Patents
Konjugirana antitijela prema ly75 za liječenje raka Download PDFInfo
- Publication number
- HRP20210410T1 HRP20210410T1 HRP20210410TT HRP20210410T HRP20210410T1 HR P20210410 T1 HRP20210410 T1 HR P20210410T1 HR P20210410T T HRP20210410T T HR P20210410TT HR P20210410 T HRP20210410 T HR P20210410T HR P20210410 T1 HRP20210410 T1 HR P20210410T1
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- Croatia
- Prior art keywords
- antibody
- antigen
- cancer
- lymphoma
- seq
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Links
- 206010028980 Neoplasm Diseases 0.000 title claims 3
- 201000011510 cancer Diseases 0.000 title claims 3
- 239000000427 antigen Substances 0.000 claims 19
- 102000036639 antigens Human genes 0.000 claims 19
- 108091007433 antigens Proteins 0.000 claims 19
- 229940079593 drug Drugs 0.000 claims 6
- 239000003814 drug Substances 0.000 claims 6
- 150000007523 nucleic acids Chemical class 0.000 claims 5
- 102000039446 nucleic acids Human genes 0.000 claims 5
- 108020004707 nucleic acids Proteins 0.000 claims 5
- 206010025323 Lymphomas Diseases 0.000 claims 4
- 239000013604 expression vector Substances 0.000 claims 4
- 230000001105 regulatory effect Effects 0.000 claims 4
- 101001018034 Homo sapiens Lymphocyte antigen 75 Proteins 0.000 claims 3
- 102100033486 Lymphocyte antigen 75 Human genes 0.000 claims 3
- 125000003275 alpha amino acid group Chemical group 0.000 claims 3
- 208000003950 B-cell lymphoma Diseases 0.000 claims 2
- 208000031671 Large B-Cell Diffuse Lymphoma Diseases 0.000 claims 2
- 206010035226 Plasma cell myeloma Diseases 0.000 claims 2
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- 206010012818 diffuse large B-cell lymphoma Diseases 0.000 claims 2
- KQODQNJLJQHFQV-UHFFFAOYSA-N (-)-hemiasterlin Natural products C1=CC=C2C(C(C)(C)C(C(=O)NC(C(=O)N(C)C(C=C(C)C(O)=O)C(C)C)C(C)(C)C)NC)=CN(C)C2=C1 KQODQNJLJQHFQV-UHFFFAOYSA-N 0.000 claims 1
- KQODQNJLJQHFQV-MKWZWQCGSA-N (e,4s)-4-[[(2s)-3,3-dimethyl-2-[[(2s)-3-methyl-2-(methylamino)-3-(1-methylindol-3-yl)butanoyl]amino]butanoyl]-methylamino]-2,5-dimethylhex-2-enoic acid Chemical compound C1=CC=C2C(C(C)(C)[C@@H](C(=O)N[C@H](C(=O)N(C)[C@H](\C=C(/C)C(O)=O)C(C)C)C(C)(C)C)NC)=CN(C)C2=C1 KQODQNJLJQHFQV-MKWZWQCGSA-N 0.000 claims 1
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims 1
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- 208000026310 Breast neoplasm Diseases 0.000 claims 1
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- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 claims 1
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- 208000027190 Peripheral T-cell lymphomas Diseases 0.000 claims 1
- 206010038389 Renal cancer Diseases 0.000 claims 1
- 208000000453 Skin Neoplasms Diseases 0.000 claims 1
- 208000005718 Stomach Neoplasms Diseases 0.000 claims 1
- 208000031672 T-Cell Peripheral Lymphoma Diseases 0.000 claims 1
- 206010042971 T-cell lymphoma Diseases 0.000 claims 1
- 208000027585 T-cell non-Hodgkin lymphoma Diseases 0.000 claims 1
- 208000024770 Thyroid neoplasm Diseases 0.000 claims 1
- 208000003721 Triple Negative Breast Neoplasms Diseases 0.000 claims 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims 1
- 108010044540 auristatin Proteins 0.000 claims 1
- HXCHCVDVKSCDHU-LULTVBGHSA-N calicheamicin Chemical compound C1[C@H](OC)[C@@H](NCC)CO[C@H]1O[C@H]1[C@H](O[C@@H]2C\3=C(NC(=O)OC)C(=O)C[C@](C/3=C/CSSSC)(O)C#C\C=C/C#C2)O[C@H](C)[C@@H](NO[C@@H]2O[C@H](C)[C@@H](SC(=O)C=3C(=C(OC)C(O[C@H]4[C@@H]([C@H](OC)[C@@H](O)[C@H](C)O4)O)=C(I)C=3C)OC)[C@@H](O)C2)[C@@H]1O HXCHCVDVKSCDHU-LULTVBGHSA-N 0.000 claims 1
- 229930195731 calicheamicin Natural products 0.000 claims 1
- 239000000969 carrier Substances 0.000 claims 1
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- AMRJKAQTDDKMCE-UHFFFAOYSA-N dolastatin Chemical compound CC(C)C(N(C)C)C(=O)NC(C(C)C)C(=O)N(C)C(C(C)C)C(OC)CC(=O)N1CCCC1C(OC)C(C)C(=O)NC(C=1SC=CN=1)CC1=CC=CC=C1 AMRJKAQTDDKMCE-UHFFFAOYSA-N 0.000 claims 1
- 229930188854 dolastatin Natural products 0.000 claims 1
- 201000004101 esophageal cancer Diseases 0.000 claims 1
- 201000003444 follicular lymphoma Diseases 0.000 claims 1
- 206010017758 gastric cancer Diseases 0.000 claims 1
- 201000010536 head and neck cancer Diseases 0.000 claims 1
- 208000014829 head and neck neoplasm Diseases 0.000 claims 1
- 108010057806 hemiasterlin Proteins 0.000 claims 1
- 229930187626 hemiasterlin Natural products 0.000 claims 1
- 210000003701 histiocyte Anatomy 0.000 claims 1
- 238000002955 isolation Methods 0.000 claims 1
- 201000010982 kidney cancer Diseases 0.000 claims 1
- 208000032839 leukemia Diseases 0.000 claims 1
- 201000007270 liver cancer Diseases 0.000 claims 1
- 208000014018 liver neoplasm Diseases 0.000 claims 1
- 201000005202 lung cancer Diseases 0.000 claims 1
- 208000020816 lung neoplasm Diseases 0.000 claims 1
- 210000004698 lymphocyte Anatomy 0.000 claims 1
- 210000003563 lymphoid tissue Anatomy 0.000 claims 1
- 201000007919 lymphoplasmacytic lymphoma Diseases 0.000 claims 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 201000007924 marginal zone B-cell lymphoma Diseases 0.000 claims 1
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- 201000002528 pancreatic cancer Diseases 0.000 claims 1
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- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 201000000849 skin cancer Diseases 0.000 claims 1
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- 238000006467 substitution reaction Methods 0.000 claims 1
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- 201000002510 thyroid cancer Diseases 0.000 claims 1
- LZAJKCZTKKKZNT-PMNGPLLRSA-N trichothecene Chemical compound C12([C@@]3(CC[C@H]2OC2C=C(CCC23C)C)C)CO1 LZAJKCZTKKKZNT-PMNGPLLRSA-N 0.000 claims 1
- 229930013292 trichothecene Natural products 0.000 claims 1
- 208000022679 triple-negative breast carcinoma Diseases 0.000 claims 1
- 201000005112 urinary bladder cancer Diseases 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
- C07K16/18—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
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- A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
- A61K47/6803—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
- A61K47/68033—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being a maytansine
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Claims (15)
1. Izolirano antitijelo, ili njegov antigen-vezujući dio, koje se veže za LY75, pri čemu navedeno antitijelo sadrži:
a) varijabilnu regiju teškog lanca koja sadrži:
i) prvi vhCDR koji sadrži SEQ ID NO: 5;
ii) drugi vhCDR koji sadrži SEQ ID NO: 6; i
iii) treći vhCDR koji sadrži SEQ ID NO: 7; i
b) varijabilnu regiju lakog lanca koja sadrži:
i) prvi vlCDR koji sadrži SEQ ID NO: 8;
ii) drugi vlCDR koji sadrži SEQ ID NO: 9; i
iii) treći vlCDR koji sadrži SEQ ID NO: 10,
pri čemu bilo koja od jedne ili više od gore navedenih SEQ ID NO neovisno sadrže jednu ili dvije amino-kiselinske supstitucije i pri čemu je antitijelo internalizirano.
2. Izolirano antitijelo, ili njegov antigen-vezujući dio, koje se veže za LY75, pri čemu navedeno antitijelo sadrži:
a) varijabilnu regiju teškog lanca koja sadrži:
i) prvi vhCDR koji sadrži SEQ ID NO: 5;
ii) drugi vhCDR koji sadrži SEQ ID NO: 6; i
iii) treći vhCDR koji sadrži SEQ ID NO: 7; i
b) varijabilnu regiju lakog lanca koja sadrži:
i) prvi vlCDR koji sadrži SEQ ID NO: 8;
ii) drugi vlCDR koji sadrži SEQ ID NO: 9; i
iii) treći vlCDR koji sadrži SEQ ID NO: 10.
3. Izolirano antitijelo ili njegov antigen-vezujući dio u skladu sa patentnim zahtjevom 1 ili patentnim zahtjevom 2, koje sadrži teški lanac koji ima najmanje 80%, 85%, 90%, 95% ili 99% identiteta amino-kiselinske sekvence sa SEQ ID NO: 1 i laki lanac koji ima najmanje 80%, 85%, 90%, 95% ili 99% identiteta amino-kiselinske sekvence sa SEQ ID NO: 2.
4. Izolirano antitijelo ili njegov antigen-vezujući dio u skladu sa bilo kojim od patentnih zahtjeva 1 do 3 koje dodatno sadrži kovalentno vezani ostatak, izborno pri čemu je navedeni ostatak lijek.
5. Izolirano antitijelo ili njegov antigen-vezujući dio u skladu sa patentnim zahtjevom 4, naznačeno time što je navedeni lijek odabran iz grupe koja se sastoji od majtansinoida, dolastatina, hemiasterlina, auristatina, trihotecena, kaliheamicina, CC1065 i njihovih derivata, poželjno pri čemu je navedeni lijek majtansinoid odabran iz grupe koja se sastoji od DM4 i DM1.
6. Farmaceutski pripravak koji sadrži antitijelo ili njegov antigen-vezujući dio u skladu sa bilo kojim od prethodnih patentnih zahtjeva, zajedno sa jednim ili više farmaceutski prihvatljivih razrjeđivača, ekscipijenata ili nosača.
7. Nukleinska kiselina koja kodira:
i) teški lanac antitijela ili njegov antigen-vezujući dio prema bilo kojem od patentnih zahtjeva 1 do 5; i
ii) laki lanac antitijela ili njegov antigen-vezujući dio prema bilo kojem od patentnih zahtjeva 1 do 5.
8. Vektor ekspresije koji sadrži jednu ili obje od nukleinskih kiselina prema patentnom zahtjevu 7 operativno povezane sa jednim ili više regulatornih elemenata.
9. Stanica domaćina koja sadrži:
(i) vektor ekspresije koji sadrži nukleinske kiseline prema patentnom zahtjevu 7 operativno povezane sa jednim ili više regulatornih elemenata; ili
(ii) prvi vektor ekspresije koji sadrži nukleinsku kiselinu koja kodira teški lanac antitijela ili njegov antigen-vezujući dio prema patentnom zahtjevu 7 operativno povezanu sa jednim ili više regulatornih elemenata i drugi vektor ekspresije koji sadrži nukleinsku kiselinu koja kodira laki lanac antitijela ili njegov antigen-vezujući dio prema patentnom zahtjevu 7 operativno povezanu sa jednim ili više regulatornih elemenata.
10. Postupak za izradu antitijela ili njegovog antigen-vezujućeg dijela, koji sadrži uzgajanje stanice domaćina u skladu sa patentnim zahtjevom 9 pod uvjetima gdje se antitijelo ili njegov antigen-vezujući dio izražava i izborno izoliranje antitijela ili njegovog antigen-vezujućeg dijela.
11. Antitijelo ili njegov antigen-vezujući dio u skladu sa bilo kojim od patentnih zahtjeva 1 do 5 za uporabu u liječenju raka.
12. Antitijelo ili njegov antigen-vezujući dio za uporabu u skladu sa patentnim zahtjevom 11, naznačeno time što je antitijelo ili njegov antigen-vezujući dio internaliziran stanicom koja izražava LY75.
13. Antitijelo ili njegov antigen-vezujući dio za uporabu u skladu sa patentnim zahtjevom 11 ili 12, naznačeno time što antitijelo ili antigen-vezujući dio sadrži kovalentno vezan lijek konjugat, poželjno, pri čemu je kovalentno vezan lijek konjugat majtansinoid, poželjnije DM4.
14. Antitijelo ili njegov antigen-vezujući dio za uporabu u skladu sa bilo kojim od patentnih zahtjeva 11 do 13 naznačeno time što je navedeni rak odabran iz grupe koja se sastoji od raka gušterače, raka jajnika, raka dojke poželjno trostruko negativnog raka dojke, kolorektalnog raka, raka jednjaka, raka kože, raka štitne žlijezde, raka pluća, raka bubrega, raka jetre, raka glave i vrata, raka mjehura, raka želuca, leukemije, poželjno akutne mijeloidne leukemije ili kronične limfocitne leukemije, mijeloma, poželjno multiplog mijeloma i limfoma, poželjno difuznog krupnog B-staničnog limfoma (DLBCL), B-staničnog limfoma, folikularnog limfoma, limfoma plaštnih stanica, limfoma limfoidnog tkiva povezanog sa mukozom (MALT), T-stanicama/histiocitima bogatog B-staničnog limfoma, Burkittovog limfoma, limfoplazmocitnog limfoma, limfoma malih limfocita, limfoma marginalne zone, T-staničnog limfoma, perifernog T- staničnog limfoma, anaplastičnog krupnostaničnog limfoma i angioimunoblastnog T- staničnog limfoma.
15. Antitijelo, ili njegov antigen-vezujući dio, u skladu sa bilo kojim od patentnih zahtjeva 1 do 5 za uporabu u terapiji ili za uporabu kao medikament.
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GB201809746D0 (en) * | 2018-06-14 | 2018-08-01 | Berlin Chemie Ag | Pharmaceutical combinations |
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