Antigen Binding Proteins To Proprotein Convertase Subtilisin Kexin Type 9 (Pcsk9) - EP3666797

EP3666797

AMGEN
Application Number
EP19207796A
Filing Date
Aug 22, 2008
Status
Granted And Under Opposition
Apr 14, 2023
Grant Date
May 17, 2023
External Links
Slate, Register, Google Patents

Bibliography

The patent EP3666797B1 was granted to Amgen on May 17, 2023 following the initial filing on Aug 22, 2008 under the application number EP19207796A . The current legal status of the patent is Granted And Under Opposition.

Patent Summary

Patent Family

Patent Family

Patent Oppositions (3)

Patent oppositions filed by competitors challenge the validity of a granted patent. These oppositions are typically based on claims of prior art, lack of novelty, or non-obviousness. They are a key part of the process for determining a patent's strength and enforceability.

CompanyOpposition DateOpposition Status

Get instant alerts for new oppositions and patent status changes

REGENERON PHARMACEUTICALSFeb 19, 2024ADMISSIBLE
SANOFI AVENTIS DEUTSCHLANDNov 10, 2023ADMISSIBLE
SANOFI AVENTIS DEUTSCHLAND SANOFI AVENTIS GROUPE SANOFI WINTHROP INDUSTRIENov 10, 2023ADMISSIBLE

Patent Citations New

Patent citations refer to prior patents cited during different phases such as opposition or international search.

Citation PhasePatent NumberPatent Link
DESCRIPTIONUS19900466008-
DESCRIPTIONUS19900574748-
DESCRIPTIONUS19900575962-
DESCRIPTIONUS19900610515-
DESCRIPTIONUS19910810279-
DESCRIPTIONUS19920853408-
DESCRIPTIONUS19920904068-
DESCRIPTIONUS19920919297-
DESCRIPTIONUS19920922649-
DESCRIPTIONUS19920990860-
DESCRIPTIONUS19930031801-
DESCRIPTIONUS19930053131-
DESCRIPTIONUS19930096762-
DESCRIPTIONUS19930112848-
DESCRIPTIONUS19930155301-
DESCRIPTIONUS19930161739-
DESCRIPTIONUS19930165699-
DESCRIPTIONUS19940209741-
DESCRIPTIONUS19940234145-
DESCRIPTIONUS19950376279-
DESCRIPTIONUS19950430938-
DESCRIPTIONUS19950462513-
DESCRIPTIONUS19950462837-
DESCRIPTIONUS19950463191-
DESCRIPTIONUS19950464582-
DESCRIPTIONUS19950464584-
DESCRIPTIONUS19950486853-
DESCRIPTIONUS19950486857-
DESCRIPTIONUS19950486859-
DESCRIPTIONUS19960724752-
DESCRIPTIONUS19960759620-
DESCRIPTIONUS19990428082-
DESCRIPTIONWO1993US00829-
DESCRIPTIONWO1994US01875-
DESCRIPTIONEP0036676
DESCRIPTIONEP0058481
DESCRIPTIONEP0088046
DESCRIPTIONEP0133988
DESCRIPTIONEP0143949
DESCRIPTIONEP0463151
DESCRIPTIONEP0546073
DESCRIPTIONEP0773288
DESCRIPTIONEP0843961
DESCRIPTIONJP3068180B
DESCRIPTIONJP3068506B
DESCRIPTIONJP3068507B
DESCRIPTIONUS2003093820
DESCRIPTIONUS3773919
DESCRIPTIONUS4179337
DESCRIPTIONUS4301144
DESCRIPTIONUS4399216
DESCRIPTIONUS4496689
DESCRIPTIONUS4640835
DESCRIPTIONUS4670417
DESCRIPTIONUS4740461
DESCRIPTIONUS4791192
DESCRIPTIONUS4912040
DESCRIPTIONUS4946778
DESCRIPTIONUS4959455
DESCRIPTIONUS5260203
DESCRIPTIONUS5530101
DESCRIPTIONUS5545806
DESCRIPTIONUS5545807
DESCRIPTIONUS5565332
DESCRIPTIONUS5585089
DESCRIPTIONUS5591669
DESCRIPTIONUS5612205
DESCRIPTIONUS5625126
DESCRIPTIONUS5625825
DESCRIPTIONUS5633425
DESCRIPTIONUS5643763
DESCRIPTIONUS5661016
DESCRIPTIONUS5693761
DESCRIPTIONUS5693762
DESCRIPTIONUS5721367
DESCRIPTIONUS5766886
DESCRIPTIONUS5770429
DESCRIPTIONUS5789215
DESCRIPTIONUS5789650
DESCRIPTIONUS5814318
DESCRIPTIONUS5859205
DESCRIPTIONUS5869619
DESCRIPTIONUS5874299
DESCRIPTIONUS5877397
DESCRIPTIONUS5885793
DESCRIPTIONUS5939598
DESCRIPTIONUS5981175
DESCRIPTIONUS6023010
DESCRIPTIONUS6054297
DESCRIPTIONUS6072035
DESCRIPTIONUS6075181
DESCRIPTIONUS6114598
DESCRIPTIONUS6133426
DESCRIPTIONUS6150584
DESCRIPTIONUS6162963
DESCRIPTIONUS6180370
DESCRIPTIONUS6255458
DESCRIPTIONUS6660843
DESCRIPTIONWO0076310
DESCRIPTIONWO0183525
DESCRIPTIONWO8801649
DESCRIPTIONWO9203918
DESCRIPTIONWO9222645
DESCRIPTIONWO9222647
DESCRIPTIONWO9222670
DESCRIPTIONWO9312227
DESCRIPTIONWO9400569
DESCRIPTIONWO9402602
DESCRIPTIONWO9425585
DESCRIPTIONWO9614436
DESCRIPTIONWO9634096
DESCRIPTIONWO9713852
DESCRIPTIONWO9824884
DESCRIPTIONWO9824893
DESCRIPTIONWO9925044
OPPOSITIONEP2615114
OPPOSITIONUS2005158303
OPPOSITIONUS2005282230
OPPOSITIONUS2007059312
OPPOSITIONWO2004022718
OPPOSITIONWO2007089753
OPPOSITIONWO2008105797
OPPOSITIONWO2008125623
OPPOSITIONWO2009055783
OPPOSITIONWO2009100297
OPPOSITIONWO2009100318
OPPOSITIONWO2010077854
OPPOSITIONWO9824893
OTHEREP2215124
OTHEREP2641917
OTHERWO2009100297
SEARCHWO2008125623
SEARCHWO2009100297

Non-Patent Literature (NPL) Citations New

NPL citations refer to non-patent references such as research papers, articles, or other publications cited during examination or opposition phases.

Citation PhaseReference TextLink
DESCRIPTION- BOWIE, Science, (19910000), vol. 253, pages 164 - 170-
DESCRIPTION- BRAMS et al., J.Immunol., (19980000), vol. 160, pages 2051 - 2058-
DESCRIPTION- BRENNER, Curr. Op. Struct. Biol., (19970000), vol. 7, no. 3, pages 369 - 376-
DESCRIPTION- BROWN MS et al., "Calcium cages, acid baths and recycling receptors", Nature, (19970000), vol. 388, pages 629 - 630-
DESCRIPTION- BRUNGER, A.T. et al., "Crystallography & NMR system: A new software suite for macromolecular structure detennination", Acta Crystallogr D Biol Crystallogr, (19980000), vol. 54, pages 905 - 21-
DESCRIPTION- BRUNGER, A.T. et al., "Crystallography & NMR system: A new software suite for macromolecular structure determination", Acta Crystallogr D Biol Crystallogr, (19980000), vol. 54, pages 905 - 21-
DESCRIPTION- CAPALDI et al., Biochem. Biophys. Res. Comm., (19770000), vol. 76, page 425-
DESCRIPTION- CARBALLIDO et al., Nat. Med., (20000000), vol. 6, pages 103 - 106-
DESCRIPTION- CHEUNG et al., Virology, (19900000), vol. 176, pages 546 - 552-
DESCRIPTION- CHOTHIA et al., J. Mol. Biol., (19860000), vol. 196, pages 901 - 17-
DESCRIPTION- CHOTHIA et al., Nature, (19890000), vol. 342, pages 878 - 883-
DESCRIPTION- CHOTHIALESK, J. Mol. Biol., (19870000), vol. 196, pages 901 - 917-
DESCRIPTION- CHOU, Ann. Rev. Biochem., vol. 47, pages 251 - 276-
DESCRIPTION- CHOU et al., Adv. Enzymol. Relat. Areas Mol. Biol., (19780000), vol. 47, pages 345 - 148-
DESCRIPTION- CHOU et al., Biochemistry, (19740000), vol. 113, no. 2, pages 211 - 222-
DESCRIPTION- CHOU et al., Biophys. J., (19790000), vol. 26, pages 367 - 384-
DESCRIPTION- CHOWDHURYPASTAN, Nature Biotech., (19990000), vol. 17, pages 568 - 572-
DESCRIPTION- CHU, Gene, (19810000), vol. 13, page 197-
DESCRIPTION- CO et al., Mol. Immunol., (19930000), vol. 30, pages 1361 - 1367-
DESCRIPTION- COHEN et al., "Sequence variations in PCSK9, low LDL, and protection against coronary heart disease", N Engl J Med, (20060000), vol. 354, pages 1264 - 1272-
DESCRIPTION- COSTET et al., "Hepatic PCSK9 Expression is Regulated by Nutirtional Status via Insulin and Sterol Regulatiory Element-binding Protein 1C", J. Biol. Chem., (20060000), vol. 281, pages 6211 - 6218-
DESCRIPTION- COSTET et al., "Hepatic PCSK9 expression is regulated by nutritional status via insulin and sterol regulatory element-binding protein 1 c", J. Biol. Chem., (20060000), vol. 281, no. 10, pages 6211 - 18-
DESCRIPTION- DAYHOFF, M. 0., Atlas of Protein Sequence and Structure, National Biomedical Research Foundation, (19720000), vol. 5, pages 101 - 110-
DESCRIPTION- ENGELHARD et al., Proc. Nat. Acad. Sci. (USA, (19940000), vol. 91, pages 3224 - 7-
DESCRIPTION- EPPSTEIN et al., Proc. Natl. Acad. Sci. USA, (19850000), vol. 82, pages 3688 - 3692-
DESCRIPTION- EVANS et al., J. Med. Chem., (19870000), vol. 30, page 1229-
DESCRIPTION- FAUCHERE, J., Adv. Drug Res., (19860000), vol. 15, page 29-
DESCRIPTION- GILLILAND, J. Immunol, (19990000), vol. 62, no. 6, pages 3663 - 71-
DESCRIPTION- GRAHAM et al., Virology, (19730000), vol. 52, page 456-
DESCRIPTION- GRIBSKOV, Meth. Enzym., (19900000), vol. 183, pages 146 - 159-
DESCRIPTION- GRIBSKOV, Proc. Nat. Acad. Sci. USA, (19870000), vol. 84, no. 13, pages 4355 - 4358-
DESCRIPTION- HENIKOFF et al., Proc. Natl. Acad. Sci. U.S.A., (19920000), vol. 89, pages 10915 - 10919-
DESCRIPTION- HOLM et al., Nucl. Acid. Res., (19990000), vol. 27, no. 1, pages 244 - 247-
DESCRIPTION- HOOGENBOOM et al., J. Mol. Biol., (19910000), vol. 227, page 381-
DESCRIPTION- HUDSON, Curr. Opin. Biotech., (19990000), vol. 9, pages 395 - 402-
DESCRIPTION- IFVERSEN, Sem. Immunol., (19960000), vol. 8, pages 243 - 248-
DESCRIPTION- ISHIDA et al., Cloning Stem Cells, (20020000), vol. 4, pages 91 - 102-
DESCRIPTION- JIA et al., J. Immunological Methods, (20040000), vol. 288, pages 91 - 98-
DESCRIPTION- JOHNSONWU, Nucleic Acids Res., (20000000), vol. 28, pages 214 - 8-
DESCRIPTION- JONES, D., Curr. Opin. Struct. Biol., (19970000), vol. 7, no. 3, pages 377 - 87-
DESCRIPTION- JONES, Nature, (19860000), vol. 321, pages 522 - 525-
DESCRIPTION- KEARNEY et al., J Immunol., (19790000), vol. 123, pages 1548 - 1550-
DESCRIPTION- KIRKLAND, J. lmmunol., (19860000), vol. 137, pages 3614 - 3619-
DESCRIPTION- KOSTELNY et al., J. Immunol., (19920000), vol. 148, pages 1547 - 1553-
DESCRIPTION- KYTE et al., J. Mol. Biol., (19820000), vol. 157, pages 105 - 131-
DESCRIPTION- LANGER, Chem. Tech., (19820000), vol. 12, pages 98 - 105-
DESCRIPTION- LANGER et al., J. Biomed. Mater. Res., (19810000), vol. 15, pages 167 - 277-
DESCRIPTION- MACCALLUIN, J. Mol. Biol., (19960000), vol. 5, pages 732 - 45-
DESCRIPTION- MARKS et al., J Mol Biol, (19910000), vol. 222, page 581-
DESCRIPTION- MARTENSSON et al., Immunol., (19940000), vol. 83, pages 1271 - 179-
DESCRIPTION- MARTENSSON, Immunol., (19950000), vol. 84, pages 224 - 230-
DESCRIPTION- MARTIN et al., Proc Natl Acad Sci (USA, (19890000), vol. 86, pages 9268 - 9272-
DESCRIPTION- MCCUNE et al., Science, (19880000), vol. 241, pages 1532 - 1639-
DESCRIPTION- MENDEZ et al., Nature Genetics, (19970000), vol. 15, pages 146 - 156-
DESCRIPTION- MOLDENHAUER et al., Scand. J. Immunol., (19900000), vol. 32, pages 77 - 82-
DESCRIPTION- MOREL et al., Molec. Immunol., (19880000), vol. 25, pages 7 - 15-
DESCRIPTION- MOULT J., Curr. Op. in Biotech., (19960000), vol. 7, no. 4, pages 422 - 427-
DESCRIPTION- MULLINAX et al., Proc Natl Acad Sci (USA, (19900000), vol. 87, pages 8095 - 8099-
DESCRIPTION- MURPHY, Blood, (19950000), vol. 86, pages 1946 - 1953-
DESCRIPTION- NANEVICZ, T., J. Biol. Chem., (19950000), vol. 270, no. 37, pages 21619 - 21625-
DESCRIPTION- NEEDLEMAN, J. Mol. Biol., (19700000), vol. 48, pages 443 - 453-
DESCRIPTION- OTWINOWSKI, Z.BOREK, D.MAJEWSKI, W.MINOR, W., "Multiparametric scaling of diffraction intensities", Acta Crystallogr A, (20030000), vol. 59, pages 228 - 34-
DESCRIPTION- OUGUERRAM K et al., "Apolipoprotein B100 metabolism in autosomal-dominant hypercholesterolemia related to mutations in PCSK9", Arterioscler thromb Vase Biol., (20040000), vol. 24, pages 1448 - 1453-
DESCRIPTION- RIECHMANN et al., Nature, (19880000), vol. 335, pages 256 - 259-
DESCRIPTION- RIZOGIERASCH, Ann. Rev. Biochem., (19920000), vol. 61, page 387-
DESCRIPTION- ROGUSKA et al., Prot. Engineer., (19960000), vol. 9, pages 895 - 904-
DESCRIPTION- RUDENKO, G. et al., "Structure of the LDL receptor extracellular domain at endosomal pH", Science, (20020000), vol. 298, pages 2353 - 8-
DESCRIPTION- SAITOUNEI, Molecular Biology and Evolution, (19870000), vol. 4, pages 406 - 425-
DESCRIPTION- SALDANHA, Mol Immunol, (19990000), vol. 36, pages 709 - 19-
DESCRIPTION- SAMUDRALA, "Ab Initio Protein Structure Prediction Using a Combined Hierarchical Approach", PROTEINS, Structure, Function and Genetics Suppl., (19990000), vol. 3, pages 194 - 198, XP001146416-
DESCRIPTION- SIDMAN, Biopolymers, (19830000), vol. 22, pages 547 - 556-
DESCRIPTION- SIPPL et al., Structure, (19960000), vol. 4, no. 1, pages 15 - 19-
DESCRIPTION- SMITH et al., J. Virol., (19830000), vol. 46, page 584-
DESCRIPTION- SONGSIVILAILACHMANN, Clin. Exp. Immunol., (19900000), vol. 79, pages 315 - 321-
DESCRIPTION- STAHLI, Methods in Enzymology, (19830000), vol. 9, pages 242 - 253-
DESCRIPTION- SUN X-M et al., "Evidence for effect of mutant PCSK9 on apoliprotein B secretion as the cause of unusually severe dominant hypercholesterolemia", Human Molecular Genetics, (20050000), vol. 14, pages 1161 - 1169-
DESCRIPTION- "The CCP4 suite: programs for protein crystallography", Acta Crystallogr D Biol Crystallogr, (19940000), vol. 50, pages 760 - 3-
DESCRIPTION- THOMPSON et al., Nucleic Acids Res., (19940000), vol. 22, pages 4673 - 4680-
DESCRIPTION- THORNTON et al., Nature, (19910000), vol. 354, page 105-
DESCRIPTION- VASWAMI et al., Annals of Allergy, Asthma, & Immunol., (19980000), vol. 81, page 105-
DESCRIPTION- VEBERFREIDINGER, TINS, (19850000), page 392-
DESCRIPTION- WINTER, FEBS Letts., (19980000), vol. 430, pages 92 - 94-
DESCRIPTION- ZUPNICK, A. et al., J Biol. Chem., (20060000), vol. 281, no. 29, pages 20464 - 20473-
DESCRIPTION- BISSAN AI-LAZIKANIARTHUR M. LESKCYRUS CHOTHIA, "Standard conformations for the canonical structures of immunoglobulins", Journal of Molecular Biology, (19971107), vol. 273, no. 4, doi:10.1006/jmbi.1997.1354, pages 927 - 948, XP004461383
DESCRIPTION- TIMMS KM et al., "A mutation in PCSK9 causing autosomal-dominant hypercholesterolemia in a Utah pedigree", Hum. Genet., (20040000), vol. 114, doi:10.1007/s00439-003-1071-9, pages 349 - 353, XP055264602
DESCRIPTION- PIPER, D.E. et al., "The crystal structure of PCSK9: a regulator of plasma LDL-cholesterol", Structure, (20070000), vol. 15, doi:10.1016/j.str.2007.04.004, pages 545 - 52, XP022069542
DESCRIPTION- SEIDAH NG et al., "The secretory proprotein convertase neural apoptosis-regulated convertase 1 (NARC-1): Liver regeneration and neuronal differentiation", PNAS, (20030000), vol. 100, doi:10.1073/pnas.0335507100, pages 928 - 933, XP002495458
EXAMINATION- NI Y.G., "A proprotein convertase subtilisin-like/Kexin type 9 (PCSK9) C-terminal domain antibody antigen-binding fragment inhibits PCSK9 internalisation and restores low density lipoprotein uptake", J. BIOL. CHEM, (20100423), vol. 285, no. 17, doi:10.1074/JBC.M110.113035, pages 12882 - 12891, XP002619048
EXAMINATION- YAN G NI ET AL, "A PCSK9-binding antibody that structurally mimics the EGF(A) domain of LDL-receptor reduces LDL cholesterol in vivo", JOURNAL OF LIPID RESEARCH, AMERICAN SOCIETY FOR BIOCHEMISTRY AND MOLECULAR BIOLOGY, INC, US, vol. 52, no. 1, doi:10.1194/JLR.M011445, ISSN 0022-2275, (20110101), pages 78 - 86, (20101019), XP002686538
OPPOSITION- Adnexus, A Bristol-Myers Squibb R&d Company, "CT-322 in Treating Patients With Advanced Solid Tumors and Non-Hodgkin's Lymphoma", Clinical Trials, ClinicalTrials.gov, Clinical Trials, URL: https://clinicaltrials.gov/study/NCT00374179?term=NCT00374179%20&rank=1&tab=history&a=1#version-content-panel, XP093259162-
OPPOSITION- Anonymous, "Antibody therapeutics approved or in regulatory review in the EU or US", Antibody Society, Antibody Society, URL: https://www.antibodysociety.org/resources/approved-antibodies, XP093259149-
OPPOSITION- Anonymous, "pIRES2-EGFP Vector Information", Clontech, vol. 15, no. 1, doi:10.1038/s41598-024-84295-2, Clontech, URL: http://www.synthesisgene.com/vector/pIRES2-EGFP.pdf, XP093259131-
OPPOSITION- Anonymous, "Sivastatin", Wikipedia, (20230523), pages 1 - 4, Wikipedia, URL: https://en.wikipedia.org/w/index.php?title=Simvastatin&oldid=, (20240307), XP093138866-
OPPOSITION- Anonymous, "Xolair 75 mg powder and solvent for solution for injection - ANNEX I SUMMARY OF PRODUCT CHARACTERISTICS", EMA, (20050101), vol. 13, no. 3, doi:10.3390/cancers13030404, page 404, XP093259157-
OPPOSITION- Bristol-Myers Squibb, "Single Ascending Dose Safety Study of BMS-962476 in Healthy Subjects and Patients With Elevated Cholesterol on Statins", Clinical Trials, ClinicalTrials.gov, Clinical Trials, URL: https://clinicaltrials.gov/study/NCT01587365?term=NCT01587365%20&rank=1&tab=history&a=1#version-content-panel, XP093259173-
OPPOSITION- C. J. Sweeney, E. G. Chriorean, M. M. Mita, K. P. Papadopoulos, B. Silver, M. Freed, J. Gokemeijer, C. Eaton, E. Furfine and A. W. Tolcher, "Phase I study of CT-322, first Adnectin protein therapeutic and potent inhibitor of VEGFR-2, in patients (pts) with advanced solid tumors (ST)", (20080501), Database accession no. 3523, XP002699158-
OPPOSITION- D142 - Decision of the UPC Central Division (Action No: UPC 1/2023)-
OPPOSITION- D143 - Examination Report for 08798550.3 dated 24.07.2014-
OPPOSITION- D144 - Printout from patentee’s website (www.repathahcp.com)-
OPPOSITION- D145 - Patentee's internal research plan (June 2006)-
OPPOSITION- D146 - MINUTES US COURT Delaware-
OPPOSITION- D148 - Second declaration of Prof. Horton (including CV)-
OPPOSITION- D149 - Declaration of Dr Redshaw (including CV)-
OPPOSITION- D150 - Second declaration of Prof. Schwartz-
OPPOSITION- D159 - Excerpt of deposition of N. Papadopoulos in Amgen v Sanofi-
OPPOSITION- D161 - https://clinicaltrials.gov/study-basics/glossary-
OPPOSITION- D166 - Journal impact factors-
OPPOSITION- D180 - Extract from trial transcript for US District Court case of Amgen v Sanofi-
OPPOSITION- D181 - Page 2 of Exhibit 3221 from US District Court case of Amgen v Sanof-
OPPOSITION- D182 - Extract from Brief for Respondents in Amgen v Sanofi (US Supreme Court)-
OPPOSITION- D185 - Second declaration of Prof. Boyd (including CV)-
OPPOSITION- D200 - Zetia FDA-approved label-
OPPOSITION- D201 - Declaration of Dr Riechmann-
OPPOSITION- D218: UPC INFRINGEMENT ACTION - PROPRIETOR’S STATEMENT OF CLAIM-
OPPOSITION- DUFF CHRISTOPHER J ET AL, "Antibody-mediated disruption of the interaction between PCSK9 and the low-density lipoprotein receptor.", Biochemical Journal, Published by Portland Press on behalf of the Biochemical Society., GB, GB , (20090501), vol. 419, no. 3, ISSN 0264-6021, pages 577 - 584, XP002619050-
OPPOSITION- John McCafferty and Kevin S. Johnson, "Construction and Screening of Antibody Display Libraries", John McCafferty and Kevin S. Johnson, Kay Brian K, Winter Jill, Mccafferty John, Phage Display of Peptides and Proteins, a Laboratory Manual, Burlington, Elsevier Science, (19960101), pages 79 - 111, ISBN 978-0-08-053870-9, XP093138885-
OPPOSITION- Jonathan C Cohen et al, "Sequence Variations in PCSK9, Low LDL, and Protection against Coronary Heart Disease", N Engl J Med Copyright © Massachusetts Medical Society, (20060101), pages 1264 - 72, N Engl J Med Copyright © Massachusetts Medical Society, URL: http://www.nejm.org/doi/pdf/10.1056/NEJMoa054013, XP055336902-
OPPOSITION- Lopez, D., "PCSK9: An enigmatic protease", Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, ELSEVIER, AMSTERDAM, NL, AMSTERDAM, NL , (20080202), vol. 1781, no. 4, ISSN 1388-1981, pages 184 - 191, XP022554055-
OPPOSITION- Martin S. Lipsky, Lisa K. Sharp, "From Idea to Market: The Drug Approval Process", (J Am Board Fam Pract, (20010901), vol. 14, no. 5, pages 362 - 367, XP055012825-
OPPOSITION- TSUTSUMI Y., ET AL., "CHEMICAL MODIFICATION OF NATURAL HUMAN TUMOR NECROSIS FACTOR-APHA WITH POLYETHYLENE GLYCOL INCREASES ITS ANTI-TUMOR POTENCY.", JAPANESE JOURNAL OF CANCER RESEARCH, AMSTERDAM, NL, NL , (19940101), vol. 85., no. 01., pages 09 - 12., XP002913448-
OPPOSITION- Marvin C. McMaster, "12 Drug Discovery and Benchtop LC/MS", Marvin C. McMaster, MARVIN C. McMASTER, LCS A Practical User's Guide, Wiley-Interscience, (20050101), pages 111 - 118, doi:10.1002/0471736589.ch12, ISBN 0-471-65531-7, XP009561182
OPPOSITION- Conte, L.L. Chothia, C. Janin, J., "The atomic structure of protein-protein recognition sites", Journal of Molecular Biology, Academic Press, United Kingdom, United Kingdom , (19990205), vol. 285, no. 5, doi:10.1006/jmbi.1998.2439, ISSN 0022-2836, pages 2177 - 2198, XP004464323
OPPOSITION- M. Wilchek & E. A. Bayer , "Chapter 4 Avidin-Biotin Immobilisation Systems", M. Wilchek & E. A. Bayer , U.B. Sleytr, P. Messner, D. Rum and M. Sara, Immobilised Macromolecules: Application Potentials , United Kingdom, Springer, (19920101), pages 51 - 60, doi:10.1007/978-1-4471-3479-4_4, ISSN 1431-8539, ISBN 978-1-4471-3481-7, XP009560043
OPPOSITION- COLEMAN D.L., "EFFECTS OF PARABIOSIS OF OBESE WITH DIABETES AND NORMAL MICE.", Diabetologia, Springer Berlin Heidelberg, Berlin/Heidelberg, Berlin/Heidelberg, (19730101), vol. 09., doi:10.1007/BF01221857, ISSN 0012-186X, pages 294 - 298., XP000611604
OPPOSITION- Nabil G. Seidah ; Annik Prat, "The proprotein convertases are potential targets in the treatment of dyslipidemia", Journal of Molecular Medicine, Springer, Berlin, DE, Berlin, DE , (20070310), vol. 85, no. 7, doi:10.1007/s00109-007-0172-7, ISSN 1432-1440, pages 685 - 696, XP019529780
OPPOSITION- Kirsten M. Timms et al, "A mutation in PCSK9 causing autosomal-dominant hypercholesterolemia in a Utah pedigree", Human Genetics, Springer Berlin Heidelberg, Berlin/Heidelberg, Berlin/Heidelberg, (20040301), vol. 114, no. 4, doi:10.1007/s00439-003-1071-9, ISSN 0340-6717, pages 349 - 353, XP055264602
OPPOSITION- Goldstein, J.L. ; Brown, M.S., "Familial hypercholesterolemia - A genetic regulatory defect in cholesterol metabolism", AMERICAN JOURNAL OF MEDICINE., Excerpta Medica, Inc., United States, United States , (19750201), vol. 58, no. 2, doi:10.1016/0002-9343(75)90563-X, ISSN 0002-9343, pages 147 - 150, XP023221016
OPPOSITION- Weinstein, J.N. ; van Osdol, W., "The macroscopic and microscopic pharmacology of monoclonal antibodies", INTERNATIONAL JOURNAL OF IMMUNOPHARMACOLOGY, ELMSFORD,NY, US, US , (19920401), vol. 14, no. 3, doi:10.1016/0192-0561(92)90176-L, ISSN 0192-0561, pages 457 - 463, XP023812662
OPPOSITION- Eric P. Dixon , Stephen Simkins , Katherine E. Kilpatrick , "Chapter 58 - Rapid Development of Monoclonal Antibodies Using Repetitive Immunizations, Multiple Sites", Eric P. Dixon , Stephen Simkins , Katherine E. Kilpatrick , Julio E. Celis, Cell Biology. A Laboratory Handbook; Third Edition, Academic Press, (20051109), vol. 1, pages 483 - 490, doi:10.1016/B978-012164730-8/50059-9, ISBN 0-12-164731-5, XP009561183
OPPOSITION- Csala, M. Marcolongo, P. Lizak, B. Senesi, S. Margittai, E. Fulceri, R. Magyar, J.E. Benedetti, A. Banhegyi, G., "Transport and transporters in the endoplasmic reticulum", Biochimica et Biophysica Acta, ELSEVIER, AMSTERDAM, NL, AMSTERDAM, NL , (20070524), vol. 1768, no. 6, doi:10.1016/j.bbamem.2007.03.009, ISSN 0005-2736, pages 1325 - 1341, XP022095184
OPPOSITION- Piper, D.E. et al, "The Crystal Structure of PCSK9: A Regulator of Plasma LDL-Cholesterol", Structure, ELSEVIER, AMSTERDAM, NL, AMSTERDAM, NL , (20070510), vol. 15, no. 5, doi:10.1016/j.str.2007.04.004, ISSN 0969-2126, pages 545 - 552, XP022069542
OPPOSITION- HORTON JAY D ET AL, "Molecular biology of PCSK9: its role in LDL metabolism.", TRENDS IN BIOCHEMICAL SCIENCES FEB 2007, (20070201), vol. 32, no. 2, doi:10.1016/j.tibs.2006.12.008, pages 71 - 77, XP002507535
OPPOSITION- McPherson, A., "Introduction to protein crystallization", Methods, Academic Press, NL, NL , (20041101), vol. 34, no. 3, doi:10.1016/j.ymeth.2004.03.019, ISSN 1046-2023, pages 254 - 265, XP004528287
OPPOSITION- Hoogenboom, H.R. Chames, P., "Natural and designer binding sites made by phage display technology", Immunology today, ELSEVIER PUBLICATIONS, CAMBRIDGE., GB, GB , (20000801), vol. 21, no. 8, doi:10.1016/S0167-5699(00)01667-4, ISSN 0167-5699, pages 371 - 378, XP004215164
OPPOSITION- GLENNIE-MJ ET AL., "Clinical trials of antibody therapy", Immunology today, ELSEVIER PUBLICATIONS, CAMBRIDGE., GB, GB , (20000801), vol. 21, no. 8, doi:10.1016/S0167-5699(00)01669-8, ISSN 0167-5699, pages 403 - 410, XP002191166
OPPOSITION- JOSEPH A. DIMASI, RONALD W. HANSEN AND HENRY G. GRABOWSKI, "THE PRICE OF INNOVATION: NEW ESTIMATES OF DRUG DEVELOPMENT COSTS", Journal of Health Economics, North-Holland, AMSTERDAM, NL, AMSTERDAM, NL , (20030301), vol. 22, no. 2, doi:10.1016/S0167-6296(02)00126-1, ISSN 0167-6296, pages 151 - 185, XP009079032
OPPOSITION- HOOGENBOOM H R, "DESIGNING AND OPTIMIZING LIBRARY SELECTION STRATEGIES FOR GENERATING HIGH-AFFINITY ANTIBODIES", TRENDS IN BIOTECHNOLOGY., ELSEVIER PUBLICATIONS, CAMBRIDGE., GB, GB , (19970201), vol. 15, doi:10.1016/S0167-7799(97)84205-9, ISSN 0167-7799, pages 62 - 70, XP000669466
OPPOSITION- F. Pirrone, Roxana E. Iacob, John R. Engen, "Applications of hydrogen/deuterium exchange MS from 2012 to 2014", ANALYTICAL CHEMISTRY, (20150101), vol. 87, doi:10.1021/ac5040242, pages 99 - 118, XP055746626
OPPOSITION- Dong Yongzhi, Shannon Curtis, "Heterogeneous Immunosensing Using Antigen and Antibody Monolayers on Gold Surfaces with Electrochemical and Scanning Probe Detection", Analytical Chemistry, American Chemical Society, (20000601), vol. 72, no. 11, doi:10.1021/ac991450g, ISSN 0003-2700, pages 2371 - 2376, XP093259133
OPPOSITION- Dincer Ayse B., Lu Yang, Schweppe Devin K., Oh Sewoong, Noble William Stafford, "Reducing Peptide Sequence Bias in Quantitative Mass Spectrometry Data with Machine Learning", JOURNAL OF PROTEOME RESEARCH, American Chemical Society, (20220701), vol. 21, no. 7, doi:10.1021/acs.jproteome.2c00211, ISSN 1535-3893, pages 1771 - 1782, XP093241041
OPPOSITION- Dall'acqua William, Goldman Ellen R, Lin Wenhong, Teng Connie, Tsuchiya Daisuke, Li Hongmin, Ysern Xavier, Braden Bradford C, Li Yili, Smith-Gill Sandra J, Mariuzza Roy A, "A Mutational alysis ofBinding Interactions in an Antigen-Antibody Protein-Protein Comple", Biochemistry, American Chemical Society, (19980601), vol. 37, no. 22, doi:10.1021/bi980148j, ISSN 0006-2960, pages 7981 - 7991, XP093259190
OPPOSITION- Neil S. Greenspan; Enrico Di Cera, "Defining epitopes: It's not as easy as it seems", Nature Biotechnology, Nature Publishing Group US, New York, New York, (19991001), vol. 17, no. 10, doi:10.1038/13590, ISSN 1087-0156, pages 936 - 937, XP008118453
OPPOSITION- REICHERT J M ET AL, "Monoclonal antibody successes in the clinic", Nature Biotechnology, Nature Publishing Group US, New York, New York, (20050901), vol. 23, no. 9, doi:10.1038/nbt0905-1073, ISSN 1087-0156, pages 1073 - 1078, XP002555770
OPPOSITION- HOOGENBOOM H R, "Selecting and screening recombinant antibody libraries.", Nature Biotechnology, Nature Publishing Group US, New York, New York, (20050901), vol. 23, no. 9, doi:10.1038/nbt1126, ISSN 1087-0156, pages 1105 - 1116, XP002348401
OPPOSITION- ABIFADEL M, ET AL, "Mutations in PCSK9 cause autosomal dominant hypercholesterolemia.", Nature Genetics, Nature Publishing Group US, New York, New York, (20030620), vol. 34, no. 2, doi:10.1038/ng1161, ISSN 1061-4036, pages 154 - 156, XP002253513
OPPOSITION- COHEN J., ET AL., "Low LDL Cholesterol in Individuals of African Descent Resulting from Frequent Nonsense Mutations in PCSK9", Nature Genetics, Nature Publishing Group US, New York, New York, (20050201), vol. 37, no. 2, doi:10.1038/ng1509, ISSN 1061-4036, pages 161 - 165, XP008102949
OPPOSITION- Ismail Kola, John Landis, "Can the pharmaceutical industry reduce attrition rates?", Nature Reviews Drug Discovery, Nature Publishing Group, GB, GB , (20040801), vol. 3, no. 8, doi:10.1038/nrd1470, ISSN 1474-1776, pages 711 - 715, XP055599147
OPPOSITION- Scott Duncan E., Bayly Andrew R., Abell Chris, Skidmore John, "Small molecules, big targets: drug discovery faces the protein-protein interaction challenge", Nature Reviews Drug Discovery, Nature Publishing Group, GB, GB , (20160801), vol. 15, no. 8, doi:10.1038/nrd.2016.29, ISSN 1474-1776, pages 533 - 550, XP093259168
OPPOSITION- TURK BORIS, "Targeting proteases: successes, failures and future prospects.", Nature Reviews Drug Discovery, Nature Publishing Group, GB, GB , (20060901), vol. 5, no. 9, doi:10.1038/nrd2092, ISSN 1474-1776, pages 785 - 799, XP002556191
OPPOSITION- CARTER P J, "POTENT ANTIBODY THERAPEUTICS BY DESIGN", Nature Reviews Immunology, Nature Publishing Group UK, London, London, (20060407), vol. 6, doi:10.1038/nri1837, ISSN 1474-1733, pages 343 - 357, XP007901440
OPPOSITION- CUNNINGHAM DAVID, ET AL, "Structural and biophysical studies of PCSK9 and its mutants linked to familial hypercholesterolemia.", Nature Structural & Molecular Biology, Nature Publishing Group US, New York, New York , (20070501), vol. 14, no. 5, doi:10.1038/NSMB1235, ISSN 1545-9993, pages 413 - 419, XP002507497
OPPOSITION- Li Jun et al, "Secreted PCSK9 promotes LDL receptor degradation independently of proteolytic activity", Biochemical Journal, Published by Portland Press on behalf of the Biochemical Society., GB, GB , (20070901), vol. 406, no. 2, doi:10.1042/BJ20070664, ISSN 0264-6021, pages 203 - 207, XP055980671
OPPOSITION- Roguin L. P., Retegui L. A., "Monoclonal Antibodies Inducing Conformational Changes on the Antigen Molecule", SCANDINAVIAN JOURNAL OF IMMUNOLOGY, BLACKWELL SCIENCE PUBL., OXFORD, GB, GB , (20031001), vol. 58, no. 4, doi:10.1046/j.1365-3083.2003.01320.x, ISSN 0300-9475, pages 387 - 394, XP093259194
OPPOSITION- SEIDAH NABIL G, ET AL, "The secretory proprotein convertase neural apoptosis-regulated convertase 1 (NARC-1): liver regeneration and neuronal differentiation.", Proceedings of the National Academy of Sciences, National Academy of Sciences, (20030204), vol. 100, no. 3, doi:10.1073/pnas.0335507100, ISSN 0027-8424, pages 928 - 933, XP002495458
OPPOSITION- MAXWELL KARA N. , BRESLOW JAN L., "Adenoviral-mediated expression of Pcsk9 in mice results in a low-density lipoprotein receptor knockout phenotype", Proceedings of the National Academy of Sciences, National Academy of Sciences, (20040504), vol. 101, no. 18, doi:10.1073/pnas.0402133101, ISSN 0027-8424, pages 7100 - 7105, XP002493244
OPPOSITION- Maxwell Kara N. et al, "Overexpression of PCSK9 accelerates the degradation of the LDLR in a post-endoplasmic reticulum compartment", Proceedings of the National Academy of Sciences, National Academy of Sciences, (20050208), vol. 102, no. 6, doi:10.1073/pnas.0409736102, ISSN 0027-8424, pages 2069 - 2074, XP093139280
OPPOSITION- Shirya Rashid et al, "Decreased plasma cholesterol and hypersensitivity to statins in mice lacking Pcsk9", Proceedings of the National Academy of Sciences, National Academy of Sciences, (20050412), vol. 102, no. 15, doi:10.1073/pnas.0501652102, ISSN 0027-8424, pages 5374 - 5379, XP002478031
OPPOSITION- E. N. Hampton et al, "The self-inhibited structure of full-length PCSK9 at 1.9 A reveals structural homology with resistin within the C-terminal domain", Proceedings of the National Academy of Sciences, National Academy of Sciences, (20070911), vol. 104, no. 37, doi:10.1073/pnas.0703402104, ISSN 0027-8424, pages 14604 - 14609, XP055264535
OPPOSITION- Hyock Joo Kwon, et al, "Molecular basis for LDL receptor recognition by PCSK9", Proceedings of the National Academy of Sciences, National Academy of Sciences, (20080212), vol. 105, no. 6, doi:10.1073/pnas.0712064105, ISSN 0027-8424, pages 1820 - 1825, XP007912351
OPPOSITION- Mcnutt Markey C. et al, "Catalytic Activity Is Not Required for Secreted PCSK9 to Reduce Low Density Lipoprotein Receptors in HepG2 Cells", Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, US, US , (20070701), vol. 282, no. 29, doi:10.1074/jbc.C700095200, ISSN 0021-9258, pages 20799 - 20803, XP093131607
OPPOSITION- BENJANNET SUZANNE ET AL, "NARC-1/PCSK9 and its natural mutants: zymogen cleavage and effects on the low density lipoprotein (LDL) receptor and LDL cholesterol.", Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, US, US , (20041119), vol. 279, no. 47, doi:10.1074/jbc.M409699200, ISSN 0021-9258, pages 48865 - 48875, XP002480952
OPPOSITION- PARK SAHNG WOOK, MOON Y-A, HORTON J D, "Post-transcriptional regulation of low density lipoprotein receptor protein by proprotein convertase subtilisin/kexin type 9a in mouse liver.", Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, US, US , (20041126), vol. 279, no. 48, doi:10.1074/jbc.M410077200, ISSN 0021-9258, pages 50630 - 50638, XP002495459
OPPOSITION- T. S. Fisher et al, "Effects of pH and Low Density Lipoprotein (LDL) on PCSK9-dependent LDL Receptor Regulation", Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, US, US , (20070713), vol. 282, no. 28, doi:10.1074/jbc.M701634200, ISSN 0021-9258, pages 20502 - 20512, XP055265234
OPPOSITION- ZHANG DA-WEI ET AL, "Binding of proprotein convertase subtilisin/kexin type 9 to epidermal growth factor-like repeat a of low density lipoprotein receptor decreases receptor recycling and increases degradation", JOURNAL OF BIOLOGICAL CHEMISTRY, (20070601), vol. 282, no. 25, doi:10.1074/jbc.M702027200, pages 18602 - 18612, XP002574508
OPPOSITION- M. J. Bottomley et al, "Structural and Biochemical Characterization of the Wild Type PCSK9-EGF(AB) Complex and Natural Familial Hypercholesterolemia Mutants", Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, (20080101), vol. 284, no. 2, doi:10.1074/jbc.M808363200, ISSN 00219258, pages 1313 - 1323, XP055061668
OPPOSITION- Sarkar Samantha K. et al, "A transient amphipathic helix in the prodomain of PCSK9 facilitates binding to low-density lipoprotein particles", Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, US, US , (20200201), vol. 295, no. 8, doi:10.1074/jbc.RA119.010221, ISSN 0021-9258, pages 2285 - 2298, XP093040649
OPPOSITION- Zhenze Zhao et al, "Molecular Characterization of Loss-of-Function Mutations in PCSK9 and Identification of a Compound Heterozygote", The American Journal of Human Genetics, American society of human genetics , Chicago , IL, US, US , (20060901), vol. 79, no. 3, doi:10.1086/507488, ISSN 0002-9297, pages 514 - 523, XP055265231
OPPOSITION- Katherine E. Kilpatrick, Wring Stephen A., Walker Duncan H., Macklin Michael D., Payne J. Alan, Su Jui-Lan, Champion Brian R., Caterson Bruce, Mcintyre Gordon D., "Rapid Development of Affinity Matured Monoclonal Antibodies Using RIMMS", Hybridoma, (19970801), vol. 16, no. 4, doi:10.1089/hyb.1997.16.381, ISSN 0272457X, pages 381 - 389, XP055010201
OPPOSITION- Sun Xi-Ming et al, "Evidence for effect of mutant PCSK9 on apolipoprotein B secretion as the cause of unusually severe dominant hypercholesterolaemia", Human Molecular Genetics, Oxford University Press, GB, GB , (20050501), vol. 14, no. 9, doi:10.1093/hmg/ddi128, ISSN 0964-6906, pages 1161 - 1169, XP093139257
OPPOSITION- Jamie Cameron et al, "Effect of mutations in the PCSK9 gene on the cell surface LDL receptors", Human Molecular Genetics, Oxford University Press, GB, GB , (20060501), vol. 15, no. 9, doi:10.1093/hmg/ddl077, ISSN 0964-6906, pages 1551 - 1558, XP055686203
OPPOSITION- Gao Feng et al, "A common polymorphism in the LDL receptor gene has multiple effects on LDL receptor function", Human Molecular Genetics, Oxford University Press, GB, GB , (20130401), vol. 22, no. 7, doi:10.1093/hmg/dds559, ISSN 0964-6906, pages 1424 - 1431, XP093138876
OPPOSITION- D. Kuroda et al, "Computer-aided antibody design", Protein Engineering Design and Selection, IRL Press, (20121001), vol. 25, no. 10, doi:10.1093/protein/gzs024, ISSN 17410126, pages 507 - 522, XP055056463
OPPOSITION- Weiner Louis M, "Fully human therapeutic monoclonal antibodies", Journal of Immunotherapy, Lippincott Williams & Wilkins, US, US , (20060101), vol. 29, no. 1, doi:10.1097/01.cji.0000192105.24583.83, ISSN 1524-9557, pages 1 - 9, XP009118693
OPPOSITION- Alexander McPherson; Jose A. Gavira, "Introduction to protein crystallization", Acta Crystallographica Section F Structural Biology and Crystallization Communications, International Union of Crystallography - IUCr, Oxford, Oxford , (20140113), vol. 70, no. 1, doi:10.1107/S2053230X13033141, ISSN 2053-230X, pages 2 - 20, XP072457354
OPPOSITION- Jp Hughes, Rees S, Kalindjian Sb, Philpott Kl, "Principles of early drug discovery", British journal of pharmacology, Wiley-Blackwell, UK, UK , (20110301), vol. 162, no. 6, doi:10.1111/j.1476-5381.2010.01127.x, ISSN 0007-1188, pages 1239 - 1249, XP055606121
OPPOSITION- Mitchell Tracy; Chao Ginger; Sitkoff Doree; Lo Fred; Monshizadegan Hossain; Meyers Daniel; Low Simon; Russo Katie; DiBella Rose; Denhez Fabienne; Gao Mian; Myers Joseph; Duke Gerald; Witmer Mark; Miao Bowman; Ho Siew P; Khan Javed; Parker Rex A, "Pharmacologic Profile of the Adnectin BMS-962476, a Small Protein Biologic Alternative to PCSK9 Antibodies for Low-Density Lipoprotein Lowering", The journal of pharmacology and experimental therapeutics, Elsevier Inc, United States, United States, (20140801), vol. 350, no. 2, doi:10.1124/jpet.114.214221, ISSN 0022-3565, pages 412 - 424, XP009184954
OPPOSITION- Brown Michael S., Joseph L. Goldstein , "Lowering LDL—Not Only How Low, But How Long?", Science, American Association for the Advancement of Science, US, US , (20060324), vol. 311, doi:10.1126/science.1125226, ISSN 0036-8075, pages 1721 - 1723, XP093139252
OPPOSITION- Knut Erik Berge et al, "Missense Mutations in the PCSK9 Gene Are Associated With Hypocholesterolemia and Possibly Increased Response to Statin Therapy", Translational Sciences, Lippincott, Williams & Wilkins, (20060119), vol. 26, no. 5, doi:10.1161/01.ATV.0000204337.81286.1c, ISSN 1079-5642, pages 1094 - 1100, XP055144155
OPPOSITION- T. N. Wight, Mervyn Merrilees, "Proteoglycans in Atherosclerosis and Restenosis: Key Roles for Versican", Circulation Research, Lippincott Williams & Wilkins, (20040514), vol. 94, no. 9, doi:10.1161/01.RES.0000126921.29919.51, ISSN 00097330, pages 1158 - 1167, XP055055218
OPPOSITION- SHIMANO H, ET AL., "Isoform 1c of sterol regulatory element binding protein is less active than isoform 1a in livers of transgenic mice and in cultured cells", The Journal of Clinical Investigation, B M J Group, (19970301), vol. 99, no. 5, doi:10.1172/JCI119248, pages 846 - 854, XP002976194
OPPOSITION- LAGACE THOMAS A ET AL, "Secreted PCSK9 decreases the number of LDL receptors in hepatocytes and in livers of parabiotic mice", The Journal of Clinical Investigation, B M J Group, (20061101), vol. 116, no. 11, doi:10.1172/JCI29383, pages 2995 - 3005, XP002493243
OPPOSITION- Twisk Jaap et al, "The role of the LDL receptor in apolipoprotein B secretion", Journal of Clinical Investigation, (20000215), vol. 105, no. 4, doi:10.1172/JCI8623, ISSN 0021-9738, pages 521 - 532, XP093131606
OPPOSITION- Malo Jonathan, Parajuli Arun, Walker Simon W, "PCSK9: from molecular biology to clinical applications", Annals of clinical biochemistry, BRITISH MEDICAL ASSOCIATION, LONDON., GB, GB , (20200101), vol. 57, no. 1, doi:10.1177/0004563219864379, ISSN 0004-5632, pages 7 - 25, XP093259164
OPPOSITION- Holla Øystein L. et al, "Degradation of the LDL receptors by PCSK9 is not mediated by a secreted protein acted upon by PCSK9 extracellularly", BMC CELL BIOLOGY, BIOMED CENTRAL, LONDON, GB, GB , (20070301), vol. 8, no. 1, doi:10.1186/1471-2121-8-9, ISSN 1471-2121, page 9, XP021021973
OPPOSITION- GRAHAM MARK J ET AL, "Antisense inhibition of proprotein convertase subtilisin/kexin type 9 reduces serum LDL in hyperlipidemic mice", JOURNAL OF LIPID RESEARCH, American Society for Biochemistry and Molecular Biology, Inc., US, US , (20070401), vol. 48, no. 4, doi:10.1194/jlr.C600025-JLR200, ISSN 0022-2275, pages 763 - 767, XP002471923
OPPOSITION- Yan G. Ni et al, "A PCSK9-binding antibody that structurally mimics the EGF(A) domain of LDL-receptor reduces LDL cholesterol in vivo", JOURNAL OF LIPID RESEARCH, American Society for Biochemistry and Molecular Biology, Inc., US, US , (20110101), vol. 52, no. 1, doi:10.1194/jlr.m011445, ISSN 0022-2275, pages 78 - 86, XP002686538
OPPOSITION- Y.-W. Qian et al, "Secreted PCSK9 downregulates low density lipoprotein receptor through receptor-mediated endocytosis", JOURNAL OF LIPID RESEARCH, American Society for Biochemistry and Molecular Biology, Inc., US, US , vol. 48, no. 7, doi:10.1194/jlr.M700071-JLR200, ISSN 0022-2275, pages 1488 - 1498, XP055265230
OPPOSITION- Seidah Nabil G, Prat Annik, "The Multifaceted Biology of PCSK9", ENDOCRINE REVIEWS, The Endocrine Society, US, US , (20220512), vol. 43, no. 3, doi:10.1210/endrev/bnab035, ISSN 0163-769X, pages 558 - 582, XP093040633
OPPOSITION- Sacks Frank M., Campos Hannia, "Low-Density Lipoprotein Size and Cardiovascular Disease: A Reappraisal", Journal of Clinical Endocrinology and Metabolism, The Endocrine Society, US, US , (20031001), vol. 88, no. 10, doi:10.1210/jc.2003-030636, ISSN 0021-972X, pages 4525 - 4532, XP093259135
OPPOSITION- Yasmina Noubia Abdiche, Andy Yik Yeung, Irene Ni, Donna Stone, Adam Miles, Winse Morishige, Andrea Rossi, Pavel Strop, "Antibodies Targeting Closely Adjacent or Minimally Overlapping Epitopes Can Displace One Another", PloS one, Public Library of Science (PLoS), United States, United States , doi:10.1371/journal.pone.0169535, pages e0169535 - e0169535, PloS one, URL: https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0169535&type=printable, XP055736286
OPPOSITION- Geoffrey Davis, Xiao-Chi, Xiao Feng, Mary Haak-Frendscho, "Production of Human Antibodies from Transgenic Mice", Geoffrey Davis, Xiao-Chi, Xiao Feng, Mary Haak-Frendscho, Lo Benny K. C. (ed.), Antibody Engineering : Methods and Protocols; IN: IN: Methods in molecular biology , ISSN 1064-3745 ; Vol. 248, Totowa, NJ , Humana Press , (20040101), vol. 248, pages 191 - 200, doi:10.1385/1-59259-666-5:191, ISBN 978-1-58829-092-2, XP055265232
OPPOSITION- Ramasamy Indra, "Recent advances in physiological lipoprotein metabolism", CLINICAL CHEMISTRY AND LABORATORY MEDICINE, De Gruyter, DE, DE , (20140101), vol. 52, no. 12, doi:10.1515/cclm-2013-0358, ISSN 1434-6621, pages 1695 - 1727, XP093138603
OPPOSITION- Maggon Krishan, "Monoclonal Antibody "Gold Rush"", Current medicinal chemistry, Bentham, NL, NL , (20070801), vol. 14, no. 18, doi:10.2174/092986707781368504, ISSN 0929-8673, pages 1978 - 1987, XP093138895
OPPOSITION- Bregenholt Soren, et al, "Recombinant human polyclonal antibodies: A new class of therapeutic antibodies against viral infections.", Current Pharmaceutical Design, Bentham Science Publishers, NL, NL , (20060101), vol. 12, no. 16, doi:10.2174/138161206777442173, ISSN 1381-6128, pages 2007 - 2015, XP008080864
OTHER- Mcnutt, M.C., Thomas A.Lagace, Jay D.Horton , "Catalytic activity is not required for secreted PCSK9 to reduce low density lipoprotein receptors in HepG2 Cells ", J. Biological Chem., (20070720), vol. 282, no. 29, pages 20700 - 20803, XP055980668-
OTHER- Swinney David C., "Molecular Mechanism of Action (MMoA) in Drug Discovery", Annual Reports in Medicinal Chemistry, (20110101), vol. 46, no. 18, pages 301 - 317, XP093033812-
OTHER- Swinney David C., "Molecular Mechanism of Action (MMoA) in Drug Discovery", Elsevier, (20110101), vol. 46, no. 18, pages 301 - 317, XP093033812-
OTHER- COHEN J., ET AL., "Low LDL Cholesterol in Individuals of African Descent Resulting from Frequent Nonsense Mutations in PCSK9", Nature Genetics, Nature Publishing Group US, New York, New York, (20050201), vol. 37, no. 2, doi:10.1038/ng1509, ISSN 1061-4036, pages 161 - 165, XP008102949
OTHER- SEIDAH NABIL G, ET AL, "The secretory proprotein convertase neural apoptosis-regulated convertase 1 (NARC-1): liver regeneration and neuronal differentiation.", Proceedings of the National Academy of Sciences, National Academy of Sciences, (20030204), vol. 100, no. 3, doi:10.1073/pnas.0335507100, ISSN 0027-8424, pages 928 - 933, XP002495458
OTHER- Hyock Joo Kwon, et al, "Molecular basis for LDL receptor recognition by PCSK9", Proceedings of the National Academy of Sciences, National Academy of Sciences, (20080212), vol. 105, no. 6, doi:10.1073/pnas.0712064105, ISSN 0027-8424, pages 1820 - 1825, XP007912351
OTHER- Sarkar Samantha K. et al, "A transient amphipathic helix in the prodomain of PCSK9 facilitates binding to low-density lipoprotein particles", Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, US, US , (20200201), vol. 295, no. 8, doi:10.1074/jbc.RA119.010221, ISSN 0021-9258, pages 2285 - 2298, XP093040649
OTHER- Seidah Nabil G, Prat Annik, "The Multifaceted Biology of PCSK9", ENDOCRINE REVIEWS, The Endocrine Society, US, US , (20220512), vol. 43, no. 3, doi:10.1210/endrev/bnab035, ISSN 0163-769X, pages 558 - 582, XP093040633
SEARCH- PIPER ET AL, "The Crystal Structure of PCSK9: A Regulator of Plasma LDL-Cholesterol", STRUCTURE, ELSEVIER, AMSTERDAM, NL, (20070510), vol. 15, no. 5, doi:10.1016/J.STR.2007.04.004, ISSN 0969-2126, pages 545 - 552, XP022069542 [A] 1-5
SEARCH- CUNNINGHAM DAVID ET AL, "Structural and biophysical studies of PCSK9 and its mutants linked to familial hypercholesterolemia", NAT. STRUCT. MOL. BIOL, NATURE PUBLISHING GROUP US, NEW YORK, (20070501), vol. 14, no. 5, doi:10.1038/NSMB1235, ISSN 1545-9993, pages 413 - 419, XP002507497 [A] 1-5
SEARCH[ ] - DIRK J. BLOM ET AL, "A 52-Week Placebo-Controlled Trial of Evolocumab in Hyperlipidemia", NEW ENGLAND JOURNAL OF MEDICINE, (20140508), vol. 370, no. 19, doi:10.1056/NEJMoa1316222, ISSN 0028-4793, pages 1809 - 1819, XP055136587
SEARCH- MAXWELL KARA N ET AL, "Adenoviral-mediated expression of Pcsk9 in mice results in a low-density lipoprotein receptor knockout phenotype", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF USA, NATIONAL ACADEMY OF SCIENCE, WASHINGTON, DC.; US, (20040504), vol. 101, no. 18, ISSN 0027-8424, pages 7100 - 7105, XP002493244 [X] 1-2,4 * see "Materials" on pages 7100 and 7101 *
SEARCH- RASHID S ET AL, "Decreased plasma cholesterol and hypersensitivity to statins in mice lacking Pcsk9", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF USA, NATIONAL ACADEMY OF SCIENCE, WASHINGTON, DC.; US, (20050412), vol. 102, no. 15, ISSN 0027-8424, pages 5374 - 5379, XP002478031 [X] 1-2,4 * See "Antibodies and immunoblot analysis", page 5375 *
SEARCH[ ] - E. N. HAMPTON ET AL, "The self-inhibited structure of full-length PCSK9 at 1.9 A reveals structural homology with resistin within the C-terminal domain", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES, US, (20070911), vol. 104, no. 37, doi:10.1073/pnas.0703402104, ISSN 0027-8424, pages 14604 - 14609, XP055264535
SEARCH- BENJANNET SUZANNE ET AL, The proprotein convertase (PC) PCSK9 is inactivated by furin and/or PC5/6A: functional consequences of natural mutations and post-translational modifications., THE JOURNAL OF BIOLOGICAL CHEMISTRY 13 OCT 2006, VOL. 281, NR. 41, PAGE(S) 30561 - 30572, (20061013), ISSN 0021-9258, XP002506016 [X] 1-2,4 * see "experimental procedures - anti PCSK9 antibodies" page 30562 *
SEARCH- DA-WEI ZHANG ET AL, "Binding of Proprotein Convertase Subtilisin/Kexin Type 9 to Epidermal Growth Factor-like Repeat A of Low Density Lipoprotein Receptor Decreases Receptor Recycling and Increases Degradation*", JOURNAL OF BIOLOGICAL CHEMISTRY, AMERICAN SOCIETY FOR BIOCHEMISTRY AND MOLECULAR BIOLOGY, US, vol. 282, no. 25, doi:10.1074/JBC.M702027200, ISSN 0021-9258, (20070622), pages 18602 - 18612, (20070423), XP007912352 [A] 1-5
SEARCH- ZHENZE ZHAO ET AL, "Molecular Characterization of Loss-of-Function Mutations in PCSK9 and Identification of a Compound Heterozygote", AMERICAN JOURNAL OF HUMAN GENETICS, US, (20060901), vol. 79, no. 3, doi:10.1086/507488, ISSN 0002-9297, pages 514 - 523, XP055265231 [X] 1-2,4 * the whole document * [Y] 3,5
SEARCH- JAMIE CAMERON ET AL, "Effect of mutations in the PCSK9 gene on the cell surface LDL receptors", HUMAN MOLECULAR GENETICS, (20060329), vol. 15, no. 9, doi:10.1093/hmg/ddl077, ISSN 0964-6906, pages 1551 - 1558, XP055686203 [A] 1-5
SEARCH- GROZDANOV PETAR N ET AL, "Expression and localization of PCSK9 in rat hepatic cells", BIOCHEMISTRY AND CELL BIOLOGY. BIOCHIMIE ET BIOLOGIE CELLULAIRE, XX, XX, (20060201), vol. 84, no. 1, ISSN 0829-8211, pages 80 - 92, XP008095646 [X] 1-2,4 * see "antibodies" page 81 *
SEARCH[ ] - N. G. SEIDAH ET AL, "PCSK9: A Key Modulator of Cardiovascular Health", CIRCULATION RESEARCH, US, (20140314), vol. 114, no. 6, doi:10.1161/CIRCRESAHA.114.301621, ISSN 0009-7330, pages 1022 - 1036, XP055221336
SEARCH- LAGACE THOMAS A ET AL, "Secreted PCSK9 decreases the number of LDL receptors in hepatocytes and in livers of parabiotic mice", JOURNAL OF CLINICAL INVESTIGATION, AMERICAN SOCIETY FOR CLINICAL INVESTIGATION, US, (20061101), vol. 116, no. 11, ISSN 0021-9738, pages 2995 - 3005, XP002493243 [X] 1-2,4 * see "methods - antibodies" page 3003 * [Y] 3,5
SEARCH[ ] - HORTON J.D., COHEN J.C & HOBBS H.H., "PCSK9: a convertase that coordinates LDL catabolism", J. LIPID RES., (200904), vol. 50 SUPP, pages S172 - S177, XP002798712

Download Citation Report

Get a free citation report including examiner, opposition, and international search citations.

Get Citation Report

Dossier Documents

The dossier documents provide a comprehensive record of the patent’s prosecution history - including filings, correspondence, and decisions made by patent offices - and are crucial for understanding the patent’s legal journey and any challenges it may have faced during examination.

  • Date

    Description

  • Get instant alerts for new documents