HRP20230823T1 - Derivati deoksi-citidina za uporabu u terapijama raka - Google Patents
Derivati deoksi-citidina za uporabu u terapijama raka Download PDFInfo
- Publication number
- HRP20230823T1 HRP20230823T1 HRP20230823TT HRP20230823T HRP20230823T1 HR P20230823 T1 HRP20230823 T1 HR P20230823T1 HR P20230823T T HRP20230823T T HR P20230823TT HR P20230823 T HRP20230823 T HR P20230823T HR P20230823 T1 HRP20230823 T1 HR P20230823T1
- Authority
- HR
- Croatia
- Prior art keywords
- compound
- use according
- cancer
- deoxycytidine
- pharmaceutically acceptable
- Prior art date
Links
- CKTSBUTUHBMZGZ-SHYZEUOFSA-N 2'‐deoxycytidine Chemical class O=C1N=C(N)C=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 CKTSBUTUHBMZGZ-SHYZEUOFSA-N 0.000 title 1
- 238000011275 oncology therapy Methods 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims 20
- 150000003839 salts Chemical class 0.000 claims 5
- 239000012453 solvate Substances 0.000 claims 5
- 206010028980 Neoplasm Diseases 0.000 claims 4
- 239000002246 antineoplastic agent Substances 0.000 claims 4
- 201000011510 cancer Diseases 0.000 claims 4
- HMUOMFLFUUHUPE-XLPZGREQSA-N 4-amino-1-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-(hydroxymethyl)pyrimidin-2-one Chemical compound C1=C(CO)C(N)=NC(=O)N1[C@@H]1O[C@H](CO)[C@@H](O)C1 HMUOMFLFUUHUPE-XLPZGREQSA-N 0.000 claims 3
- 201000007455 central nervous system cancer Diseases 0.000 claims 3
- HMUOMFLFUUHUPE-UHFFFAOYSA-N dhmC Natural products C1=C(CO)C(N)=NC(=O)N1C1OC(CO)C(O)C1 HMUOMFLFUUHUPE-UHFFFAOYSA-N 0.000 claims 3
- 230000002265 prevention Effects 0.000 claims 3
- QBADNGFALQJSIH-XLPZGREQSA-N 4-amino-1-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-2-oxopyrimidine-5-carbaldehyde Chemical compound C1=C(C=O)C(N)=NC(=O)N1[C@@H]1O[C@H](CO)[C@@H](O)C1 QBADNGFALQJSIH-XLPZGREQSA-N 0.000 claims 2
- UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 claims 2
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 claims 2
- BPEGJWRSRHCHSN-UHFFFAOYSA-N Temozolomide Chemical compound O=C1N(C)N=NC2=C(C(N)=O)N=CN21 BPEGJWRSRHCHSN-UHFFFAOYSA-N 0.000 claims 2
- 229960000684 cytarabine Drugs 0.000 claims 2
- 229960002949 fluorouracil Drugs 0.000 claims 2
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 claims 2
- 229960005277 gemcitabine Drugs 0.000 claims 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 2
- 229960004964 temozolomide Drugs 0.000 claims 2
- DLHNIFPAUZVLLA-XLPZGREQSA-N 2'-deoxy-5-hydroxymethyl-CTP Chemical compound C1=C(CO)C(N)=NC(=O)N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)C1 DLHNIFPAUZVLLA-XLPZGREQSA-N 0.000 claims 1
- 208000003174 Brain Neoplasms Diseases 0.000 claims 1
- DLGOEMSEDOSKAD-UHFFFAOYSA-N Carmustine Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 claims 1
- 208000032612 Glial tumor Diseases 0.000 claims 1
- 206010018338 Glioma Diseases 0.000 claims 1
- UIFNWSMURHAIJK-XLPZGREQSA-N [[(2r,3s,5r)-5-(4-amino-5-formyl-2-oxopyrimidin-1-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate Chemical compound C1=C(C=O)C(N)=NC(=O)N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)C1 UIFNWSMURHAIJK-XLPZGREQSA-N 0.000 claims 1
- 229940084910 gliadel Drugs 0.000 claims 1
- 208000005017 glioblastoma Diseases 0.000 claims 1
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 239000000825 pharmaceutical preparation Substances 0.000 claims 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/06—Pyrimidine radicals
- C07H19/073—Pyrimidine radicals with 2-deoxyribosyl as the saccharide radical
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
- A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
- A61K31/7068—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
- A61K31/7072—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
- A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
- A61K31/7068—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/17—Amides, e.g. hydroxamic acids having the group >N—C(O)—N< or >N—C(S)—N<, e.g. urea, thiourea, carmustine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/06—Pyrimidine radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/06—Pyrimidine radicals
- C07H19/10—Pyrimidine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Molecular Biology (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biotechnology (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Engineering & Computer Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Claims (15)
1. Spoj formule (Ila):
[image]
ili njegov stereoizomer, solvat, tautomer ili farmaceutski prihvatljiva sol za uporabu u liječenju ili prevenciji raka središnjeg živčanog sustava; naznačen time što:
X je -(CH2)n-X’, pri čemu je n od 0 do 6 i X’ je -CHO, -OH, -OR ili –
OC(=O)R, gdje je R metil; Rl je -OH ili -O(P(=O)(OH)O)nH gdje je n od 1 do
3; i
R2 je -OH.
2. Spoj za uporabu prema zahtjevu 1, naznačen time što spoj je spoj formule (Illa) ili (IIIc), ili njegov stereoizomer, solvat, tautomer ili farmaceutski prihvatljiva sol:
[image]
[image]
naznačen time što je X kako je definirano u zahtjevu 1.
3. Spoj za uporabu prema zahtjevu 1 ili zahtjevu 2, naznačen time što X je
a) -CHO ili -CH2OH; ili
b) -CH2OCH3 ili -CH2OC(=O)CH3.
4. Spoj za uporabu prema bilo kojem od zahtjeva 1 do 3, naznačen time što X je -CHO ili -CH2OH, poželjno CH2OH.
5. Spoj za uporabu prema bilo kojem od zahtjeva 1 do 4, naznačen time što je spoj 5-formil-2'-deoksicitidin, 5-hidroksimetil-2’-deoksicitidin, 5-formil-2’-deoksicitidin-5’-trifosfat ili 5-hidroksimetil-2’-deoksicitidin-5’-trifosfat, ili njihov stereoizomer, solvat, tautomer ili farmaceutski prihvatljiva sol.
6. Spoj za uporabu prema zahtjevu 5, naznačen time što je spoj 5-formil-2’-deoksicitidin ili 5-hidroksimetil-2’-deoksicitidin, ili njegov stereoizomer, solvat, tautomer ili farmaceutski prihvatljiva sol.
7. Spoj za uporabu prema zahtjevu 6, naznačen time što je spoj 5-hidroksimetil-2’-deoksicitidin ili njegov stereoizomer, solvat, tautomer ili farmaceutski prihvatljiva sol.
8. Spoj za uporabu prema bilo kojem od zahtjeva 1 do 7, naznačen time što rak je rak mozga.
9. Spoj za uporabu prema bilo kojem od zahtjeva 1 do 8, naznačen time što je rak gliom.
10. Spoj za uporabu prema zahtjevu 9, naznačen time što je rak glioblastom.
11. Spoj za uporabu prema bilo kojem od zahtjeva 1 do 10, naznačen time što rak je otporan na liječenje gemcitabinom, citarabinom, temozolomidom ili 5-fluorouracilom.
12. Spoj za uporabu prema bilo kojem od zahtjeva 1 do 11, naznačen time što navedeno liječenje nadalje uključuje primjenu daljnjeg sredstva protiv raka.
13. Komplet koji sadrži spoj kako je definiran u bilo kojem od zahtjeva 1 do 7 i nadalje sredstvo protiv raka za uporabu u liječenju ili prevenciji raka središnjeg živčanog sustava.
14. Farmaceutski pripravak za uporabu u liječenju ili prevenciji raka središnjeg živčanog sustava koji sadrži spoj kako je definiran u bilo kojem od zahtjeva 1 do 7 i izborno nadalje sredstvo protiv raka, zajedno s jednim ili više farmaceutski prihvatljivih ekscipijenata.
15. Spoj za uporabu prema zahtjevu 12, komplet za uporabu prema zahtjevu 13 ili farmaceutski pripravak za uporabu prema zahtjevu 14, naznačen time što je nadalje sredstvo protiv raka odabrano iz skupine koju čine gemcitabin, citarabin, temozolomid, 5-fluorouracil i gliadel (RTM ).
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB1901427.3A GB2580963B (en) | 2019-02-01 | 2019-02-01 | Cancer therapies |
| PCT/EP2020/052632 WO2020157335A1 (en) | 2019-02-01 | 2020-02-03 | Deoxy- cytidine or uridine derivatives for use in cancer therapies |
| EP20703447.1A EP3917538B1 (en) | 2019-02-01 | 2020-02-03 | Deoxy- cytidine derivatives for use in cancer therapies |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20230823T1 true HRP20230823T1 (hr) | 2023-10-27 |
Family
ID=65998012
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20230823TT HRP20230823T1 (hr) | 2019-02-01 | 2020-02-03 | Derivati deoksi-citidina za uporabu u terapijama raka |
Country Status (24)
| Country | Link |
|---|---|
| US (1) | US11963973B2 (hr) |
| EP (2) | EP4233879A1 (hr) |
| JP (2) | JP7314289B2 (hr) |
| KR (2) | KR102653041B1 (hr) |
| CN (2) | CN118078850A (hr) |
| AU (2) | AU2020215801B2 (hr) |
| BR (1) | BR112021014898A2 (hr) |
| CA (1) | CA3126512A1 (hr) |
| DK (1) | DK3917538T3 (hr) |
| ES (1) | ES2956508T3 (hr) |
| FI (1) | FI3917538T3 (hr) |
| GB (1) | GB2580963B (hr) |
| HR (1) | HRP20230823T1 (hr) |
| HU (1) | HUE062708T2 (hr) |
| IL (1) | IL285207A (hr) |
| LT (1) | LT3917538T (hr) |
| MX (1) | MX2021009206A (hr) |
| PL (1) | PL3917538T3 (hr) |
| PT (1) | PT3917538T (hr) |
| RS (1) | RS64515B1 (hr) |
| SG (1) | SG11202107281XA (hr) |
| SI (1) | SI3917538T1 (hr) |
| WO (1) | WO2020157335A1 (hr) |
| ZA (1) | ZA202106190B (hr) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2020334060A1 (en) * | 2019-08-19 | 2022-03-24 | Zogenix, Inc. | Polymorphic forms of deoxycytidine, compositions comprising the same and uses |
| WO2023068404A1 (ko) * | 2021-10-21 | 2023-04-27 | 한국생명공학연구원 | Eml4-alk 양성 비소세포폐암 환자의 치료 약물 선택을 위한 정보 제공 방법 및 alk 저해제 내성 비소세포폐암 치료용 조성물 |
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| US5545629A (en) * | 1994-04-12 | 1996-08-13 | Montefiore Medical Center | 5-ethoxy-2'-deoxyuridines |
| WO1996026743A1 (en) * | 1995-03-01 | 1996-09-06 | Human Gene Therapy Research Institute | Radiation enhanced gene therapy for treatment of tumors |
| CN1205640A (zh) * | 1995-12-22 | 1999-01-20 | 东卡罗来纳大学 | 治疗以胞苷脱氨酶或脱氧胞苷脱氨酶过量表达为特征的失调的方法 |
| US6136791A (en) | 1995-12-22 | 2000-10-24 | East Carolina University | Agent and method for treating disorders associated with cytidine deaminase or deoxycytidine deaminase overexpression |
| EP1156827B1 (en) | 1999-03-01 | 2006-09-20 | Halogenetics, Inc. | USE OF COMPOSITIONS COMPRISING CldC AS RADIOSENSITIZERS IN THE TREATMENT OF NEOPLASTIC DISEASES |
| AU6792700A (en) * | 1999-08-20 | 2001-03-19 | Research Foundation Of The State University Of New York, The | 5-propynylpyrimidine derivatives as cytotoxic enzyme inhibitors |
| WO2008085611A2 (en) * | 2006-11-27 | 2008-07-17 | University Of Miami | Designer theraphy of pancreatic tumors |
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| US20110230433A1 (en) * | 2010-03-16 | 2011-09-22 | University Of Washington | Compositions and methods for treatment of cancer |
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| CZ309218B6 (cs) * | 2014-08-26 | 2022-06-01 | Univerzita Palackého v Olomouci | Způsob stanovení aktivity enzymů přeměňujících cytosinové deriváty na uracilové deriváty v buňkách a tkáních |
| DE102014113936A1 (de) * | 2014-09-25 | 2016-03-31 | Christoph Pallua | Krebsmedikament |
| US20190328783A1 (en) * | 2016-04-15 | 2019-10-31 | Cellectis | A method of engineering prodrug-specific hypersensitive t-cells for immunotherapy by gene expression |
| AU2017354876A1 (en) * | 2016-11-04 | 2019-06-20 | Qiagen Sciences, Llc | Thiol-containing cleave reagents and oxidative wash |
| GB201913030D0 (en) | 2019-09-10 | 2019-10-23 | Francis Crick Institute Ltd | Treatment of hr deficient cancer |
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