HRP20170613T1 - Antikoagulacijski protuotrovi - Google Patents
Antikoagulacijski protuotrovi Download PDFInfo
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- HRP20170613T1 HRP20170613T1 HRP20170613TT HRP20170613T HRP20170613T1 HR P20170613 T1 HRP20170613 T1 HR P20170613T1 HR P20170613T T HRP20170613T T HR P20170613TT HR P20170613 T HRP20170613 T HR P20170613T HR P20170613 T1 HRP20170613 T1 HR P20170613T1
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- Prior art keywords
- dabigatran
- antibody
- seq
- etexilate
- patient
- Prior art date
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- 239000000729 antidote Substances 0.000 title claims 2
- 239000003146 anticoagulant agent Substances 0.000 title 1
- 229940127219 anticoagulant drug Drugs 0.000 title 1
- 229940075522 antidotes Drugs 0.000 title 1
- 229960003850 dabigatran Drugs 0.000 claims 30
- YBSJFWOBGCMAKL-UHFFFAOYSA-N dabigatran Chemical compound N=1C2=CC(C(=O)N(CCC(O)=O)C=3N=CC=CC=3)=CC=C2N(C)C=1CNC1=CC=C(C(N)=N)C=C1 YBSJFWOBGCMAKL-UHFFFAOYSA-N 0.000 claims 30
- 229960000288 dabigatran etexilate Drugs 0.000 claims 9
- KSGXQBZTULBEEQ-UHFFFAOYSA-N dabigatran etexilate Chemical compound C1=CC(C(N)=NC(=O)OCCCCCC)=CC=C1NCC1=NC2=CC(C(=O)N(CCC(=O)OCC)C=3N=CC=CC=3)=CC=C2N1C KSGXQBZTULBEEQ-UHFFFAOYSA-N 0.000 claims 9
- 239000008194 pharmaceutical composition Substances 0.000 claims 8
- 238000006386 neutralization reaction Methods 0.000 claims 7
- 150000003839 salts Chemical class 0.000 claims 7
- 229940002612 prodrug Drugs 0.000 claims 6
- 239000000651 prodrug Substances 0.000 claims 6
- 239000012634 fragment Substances 0.000 claims 5
- 230000035602 clotting Effects 0.000 claims 4
- 238000000034 method Methods 0.000 claims 3
- 206010053567 Coagulopathies Diseases 0.000 claims 2
- 108010021625 Immunoglobulin Fragments Proteins 0.000 claims 2
- 102000008394 Immunoglobulin Fragments Human genes 0.000 claims 2
- 238000004458 analytical method Methods 0.000 claims 2
- 238000003556 assay Methods 0.000 claims 2
- 238000007820 coagulation assay Methods 0.000 claims 2
- 206010056867 Activated protein C resistance Diseases 0.000 claims 1
- 102000008946 Fibrinogen Human genes 0.000 claims 1
- 108010049003 Fibrinogen Proteins 0.000 claims 1
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 claims 1
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 claims 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims 1
- 230000015556 catabolic process Effects 0.000 claims 1
- 238000004113 cell culture Methods 0.000 claims 1
- 238000012258 culturing Methods 0.000 claims 1
- 239000000539 dimer Substances 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 229940012952 fibrinogen Drugs 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 108020004707 nucleic acids Proteins 0.000 claims 1
- 102000039446 nucleic acids Human genes 0.000 claims 1
- 150000007523 nucleic acids Chemical class 0.000 claims 1
- 108090000765 processed proteins & peptides Proteins 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 claims 1
Classifications
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- 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
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39583—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials not provided for elsewhere, e.g. haptens, coenzymes
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/02—Antidotes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
-
- 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
-
- 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
- G01N33/86—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving blood coagulating time or factors, or their receptors
-
- 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
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/54—F(ab')2
-
- 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
- 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
- C07K2317/569—Single domain, e.g. dAb, sdAb, VHH, VNAR or nanobody®
-
- 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
- C07K2317/626—Diabody or triabody
-
- 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
- C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2500/00—Screening for compounds of potential therapeutic value
- G01N2500/02—Screening involving studying the effect of compounds C on the interaction between interacting molecules A and B (e.g. A = enzyme and B = substrate for A, or A = receptor and B = ligand for the receptor)
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2500/00—Screening for compounds of potential therapeutic value
- G01N2500/10—Screening for compounds of potential therapeutic value involving cells
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- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Immunology (AREA)
- Hematology (AREA)
- Molecular Biology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biochemistry (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Biomedical Technology (AREA)
- Microbiology (AREA)
- Urology & Nephrology (AREA)
- Genetics & Genomics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- Diabetes (AREA)
- Cell Biology (AREA)
- Mycology (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Physics & Mathematics (AREA)
- Food Science & Technology (AREA)
- Biotechnology (AREA)
- Analytical Chemistry (AREA)
- Toxicology (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Claims (20)
1. Molekula protutijela koja ima specifičnost vezanja na dabigatran, naznačena time, da obuhvaća varijabilnu domenu jakog lanca s CDR1 od SEQ ID NO:1, CDR2 od SEQ ID NO:7, CDR3 od SEQ ID NO:10, i varijabilnu domenu slabog lanca s CDR1 od SEQ ID NO:13, CDR2 od SEQ ID NO:14, i CDR3 od SEQ ID NO:15.
2. Molekula protutijela prema zahtjevu 1, naznačena time, da obuhvaća varijabilnu domenu jakog lanca od SEQ ID NO:24, i varijabilnu domenu slabog lanca od SEQ ID NO:27.
3. Molekula protutijela prema bilo kojem od prethodnih zahtjeva,
naznačena time, da je ona monoklonalno protutijelo, ljudsko protutijelo, humanizirano protutijelo, kimerno protutijelo, fragment protutijela, posebno fragment Fab, fragment Fab’, ili fragment F(ab’)2, protutijelo jednostrukog lanca, posebno varijabilni fragment jednostrukog lanca (scFv), mali modularni imunofarmaceutik (SmallModularImmunopharmaceutical – SMIP), ili diabody (dimer fragmenta imunoglobulina).
4. Molekula protutijela prema zahtjevu 3, naznačena time, da je ona scFv, pri čemu su varijabilna domena jakog lanca i varijabilna domena slabog lanca međusobno spojene kroz peptidnu poveznicu odabranu iz skupine koju čine: SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, i SEQ ID NO:31.
5. Molekula protutijela prema zahtjevu 3, naznačena time, da ima jaki lanac koji obuhvaća SEQ ID NO:40, i slabi lanac koji obuhvaća SEQ ID NO:35.
6. Protutijelo prema zahtjevu 3, naznačeno time, da je ono Fab-molekula s jednim Fd-fragmentom koji obuhvaća SEQ ID NO:36, ili SEQ ID NO:41, i sa slabim lancem koji obuhvaća SEQ ID NO:37.
7. Protutijelo prema zahtjevu 6, naznačeno time, da Fd-fragment obuhvaća SEQ ID NO:36, i ima slabi lanac koji obuhvaća SEQ ID NO:37.
8. Molekula protutijela prema bilo kojem od prethodnih zahtjeva,
naznačena time, da se upotrebljava kao lijek.
9. Molekula protutijela prema bilo kojem od prethodnih zahtjeva,
naznačena time, da se upotrebljava kao protuotrov protiv terapije dabigatrana ili dabigatran-eteksilata, i/ili za poništavanje prekomjerne doze
dabigatrana ili dabigatran-eteksilata.
10. Postupak za proizvodnju molekule protutijela prema bilo kojem od prethodnih zahtjeva, naznačen time, da obuhvaća sljedeće korake:
(a) pripremanje stanice domaćina koja obuhvaća jednu ili više nukleinskih kiselina koje kodiraju navedenu molekulu protutijela u funkcionalnom spoju s kontrolnom sekvencom ekspresije;
(b) kultiviranje navedene stanice domaćina;
(c) dobivanje molekule protutijela iz stanične kulture.
11. Garnitura, naznačena time, da obuhvaća sljedeće:
(a) protutijelo prema bilo kojem od zahtjeva 1 do 7, ili njegov farmaceutski sastav;
(b) farmaceutski sastav koji obuhvaća dabigatran, dabigatran-eteksilat, predlijek od dabigatrana ili njegovu farmaceutski prihvatljivu sol;
(c) spremnik; i
(d) etiketa.
12. Garnitura prema zahtjevu 11, naznačena time, da farmaceutski prihvatljiva sol dabigatran-eteksilata je mesilatna sol.
13. Garnitura prema zahtjevu 11 ili 12, naznačena time, da je jačina od dabigatrana, dabigatran-eteksilata, predlijeka od dabigastrana ili njegove farmaceutski prihvatljive soli, između 75 mg i 300 mg, po jedinici doze, bilo jednom dnevno (QD) ili dva puta dnevno (BID).
14. Garnitura, naznačena time, da obuhvaća sljedeće:
(a) prvi farmaceutski sastav koji obuhvaća dabigatran, dabigatran-eteksilat, predlijek od dabigatrana ili njegovu farmaceutski prihvatljivu sol;
(b) drugi farmaceutski sastav koji obuhvaća protutijelo prema bilo kojem od zahtjeva 1 do 7;
(c) upute za odvojenu primjenu prvog i drugog farmaceutskog sastava kod pacijenta;
pri čemu se navedeni prvi i drugi farmaceutski sastav nalaze u odvojenim spremnicima, dok se drugi farmaceutski sastav upotrebljava za primjenu kod pacijenta kojemu je potrebna neutralizacija ili djelomična neutralizacija dabigatrana ili 1-O-acilglukuronida od dabigatrana.
15. Protutijelo prema bilo kojem od zahtjeva 1 do 7, naznačeno time, da se upotrebljava u postupku za neutralizaciju ili djelomičnu neutralizaciju dabigatrana ili 1-O-acilglukuronida od dabigatrana, kod pacijenta koji je bio podvrgnut liječenju s dabigatranom, dabigatran-eteksilatom, predlijekom od dabigatrana ili s njegovom farmaceutski prihvatljivom soli.
16. Protutijelo prema bilo kojem od zahtjeva 1 do 7, naznačeno time, da se upotrebljava u postupku za neutralizaciju ili djelomičnu neutralizaciju dabigatrana ili 1-O-acilglukuronida od dabigatrana, kod pacijenta, pri čemu to obuhvaća sljedeće:
(a) utvrđivanje da je pacijent bio podvrgnut liječenju s dabigatranom, dabigatran-eteksilatom, predlijekom od dabigatrana ili s njegovom farmaceutski prihvatljivom soli, te izvještaj o količini koju je pacijent uzeo;
(b) neutralizacija dabigatrana ili 1-O-acilglukuronida od dabigatrana pomoću protutijela prema bilo kojem od zahtjeva 1 do 9, prije nego što se poduzme testiranje ili analiza zgrušavanja ili koagulacije, u kojem/kojoj bi dabigatran ili 1-O-acilglukuronid od dabigatrana ometao točan nalaz testa ili rezultate analize;
(c) izvođenje testiranja ili analize zgrušavanja ili koagulacije na uzorku koji je uzet od pacijenta, kako bi se odredila razina formiranja ugrušaka bez prisutnosti dabigatrana ili 1-O-acilglukuronida od dabigatrana; i
(d) namještanje količine dabigatrana, dabigatran-eteksilata, predlijeka od dabigatrana ili njegove farmaceutski prihvatljive soli, za primjenu kod pacijenta u svrhu dobivanja prikladne ravnoteže između formiranja ugrušaka i njihove razgradnje kod pacijenta.
17. Protutijelo za uporabu prema zahtjevima 15 ili 16, naznačeno time, da je količina protutijela prema dabigatranu ili 1-O-acilglukuronidu od dabigatrana, u molarnom omjeru između 0,1 i 100.
18. Protutijelo za uporabu prema zahtjevu 17, naznačeno time, da je količina protutijela prema dabigatranu ili 1-O-acilglukuronidu od dabigatrana, u molarnom omjeru između 0,1 i 10.
19. Protutijelo za uporabu prema zahtjevu 16, naznačeno time, da točan nalaz testa ili rezultat analize, odgovara točnom nalazu razina fibrinogena, aktiviranoj otpornosti proteina C, ili odgovarajućim testovima.
20. Farmaceutski sastav, naznačen time, da obuhvaća protutijelo prema bilo kojem od zahtjeva 1 do 7, i farmaceutski prihvatljiv nosač.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP10151239 | 2010-01-20 | ||
| US38391410P | 2010-09-17 | 2010-09-17 | |
| PCT/EP2011/050749 WO2011089183A2 (en) | 2010-01-20 | 2011-01-20 | Anticoagulant antidotes |
| EP11703410.8A EP2525812B1 (en) | 2010-01-20 | 2011-01-20 | Anticoagulant antidotes |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20170613T1 true HRP20170613T1 (hr) | 2017-06-30 |
Family
ID=42061991
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20170613TT HRP20170613T1 (hr) | 2010-01-20 | 2017-04-14 | Antikoagulacijski protuotrovi |
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Families Citing this family (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TWI513466B (zh) | 2010-01-20 | 2015-12-21 | Boehringer Ingelheim Int | 抗凝血劑解毒劑 |
| CA2858350A1 (en) | 2011-01-14 | 2013-07-19 | The Regents Of The University Of California | Therapeutic antibodies against ror-1 protein and methods for use of same |
| EP2665751A1 (en) * | 2011-01-19 | 2013-11-27 | Bayer Intellectual Property GmbH | Binding proteins to inhibitors of coagulation factors |
| PE20140964A1 (es) * | 2011-03-30 | 2014-08-17 | Boehringer Ingelheim Int | Antidotos anticoagulantes |
| PT2785700E (pt) | 2011-11-29 | 2016-06-02 | Perosphere Inc | Agentes de reversão de anticoagulantes |
| AR095499A1 (es) | 2013-03-14 | 2015-10-21 | Bayer Healthcare Llc | ANTICUERPOS MONOCLONALES CONTRA ANTITROMBINA b |
| EP3060583A1 (en) * | 2013-10-25 | 2016-08-31 | Boehringer Ingelheim International GmbH | Anticoagulant antidotes |
| TW201623331A (zh) * | 2014-03-12 | 2016-07-01 | 普羅帝納生物科學公司 | 抗黑色素瘤細胞黏著分子（ｍｃａｍ）抗體類及使用彼等之相關方法 |
| CN105223348A (zh) * | 2014-05-26 | 2016-01-06 | 北京九强生物技术股份有限公司 | 人抗凝血酶iii的胶乳增强免疫比浊法检测试剂盒 |
| EP2980218A1 (en) | 2014-07-30 | 2016-02-03 | Rheinische Friedrich-Wilhelms-Universität Bonn | Aptamer thrombin complex for use as an antidote to direct acting thrombin inhibitors |
| EP3611507B1 (en) * | 2014-07-31 | 2021-11-24 | Haemonetics Corporation | Detection of reversal of an anticoagulant using ecarin and factor xa clotting assays |
| US10300154B2 (en) | 2014-09-17 | 2019-05-28 | David R Elmaleh | Anticoagulant derivatives for cardiovascular imaging |
| EP4205743A1 (en) | 2014-12-31 | 2023-07-05 | Shenzhen Pharmacin Co., Ltd. | Pharmaceutical composition and preparation method therefor |
| US10449195B2 (en) | 2016-03-29 | 2019-10-22 | Shenzhen Pharmacin Co., Ltd. | Pharmaceutical formulation of palbociclib and a preparation method thereof |
| US11879014B2 (en) | 2017-03-17 | 2024-01-23 | Tusk Therapeutics Ltd. | Method of treating cancer or depleting regulatory T cells in a subject by administering a human IGG1 anti-CD25 antibody |
| SG11202005908WA (en) * | 2017-12-24 | 2020-07-29 | Noile Immune Biotech Inc | Immunocompetent cell that expresses a cell surface molecule specifically recognizing human mesothelin, il-7 and ccl19 |
| TW202003034A (zh) | 2018-03-13 | 2020-01-16 | 英商塔斯克療法有限公司 | 抗-cd25抗體藥劑 |
| CA3099974A1 (en) | 2018-05-11 | 2019-11-14 | Halcyon Therapeutics, Inc. | Binding proteins and chimeric antigen receptor t cells targeting gasp-1 granules and uses thereof |
| US20210395299A1 (en) | 2018-10-29 | 2021-12-23 | Huahai Us Inc. | Novel dipeptide compounds and uses thereof |
| WO2020180489A1 (en) | 2019-03-06 | 2020-09-10 | University Of Rochester | Anticoagulant compositions and uses thereof |
| CN114306245A (zh) | 2020-09-29 | 2022-04-12 | 深圳市药欣生物科技有限公司 | 无定形固体分散体的药物组合物及其制备方法 |
| TW202321311A (zh) * | 2021-08-02 | 2023-06-01 | 日商諾伊爾免疫生物科技股份有限公司 | 與scFv等之連接子結合的抗體 |
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