IP Library › Granted Patent US 50,288
Granted Patent E1
US 50,288 · App. 18/153,894 · Granted Feb 4, 2025

Factor IX polypeptide mutant, its uses and a method for its production

Inventor: Paolo Simioni (Padua, IT)
Assignee: UNIQURE BIOPHARMA B.V.
C12N9/644A61K38/4846A61P7/04C12Y304/21022
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 50,288
App. No.
18/153,894
Granted
Feb 4, 2025
Kind
E1
Abstract

Disclosed are a modified FIX (factor IX) polypeptide comprising a leucine, cysteine, aspartic acid, glutamic acid, histidine, lysine, asparagine, glutamine or tyrosine in position 338; pharmaceutical preparations containing said modified FIX polypeptide; a nucleotide sequence coding for the modified FIX polypeptide; and a method for producing the modified FIX polypeptide.

Claims (25)

1. A pharmaceutical composition comprising:

a modified recombinant FIX (factor IX) polypeptide comprising at least 70% identity to SEQ ID NO: 2 and a leucine in position 338 of SEQ ID NO: 2; the modified recombinant FIX polypeptide in an amount suitable to provide a daily dosage comprised between 0.1 μg/kg and 400 μg/kg body weight, and

at least one pharmaceutically acceptable excipient.

2. The pharmaceutical composition according to claim 1 , wherein the polypetide comprises at least 90% identity to SEQ ID NO: 2.

3. The pharmaceutical composition according to claim 1 formulated for oral, parenteral or rectal administration or suited to administration by inhalation or insufflation.

4. A method of treatment, the method comprising administering to an individual in need thereof the pharmaceutical composition according to claim 1 .

5. The method according to claim 4 wherein the administering is performed to treat at least one coagulopathy in the individual.

6. A sequence of nucleotides encoding a modified FIX (Factor IX) polypeptide comprising at least 70% identity to SEQ ID NO: 2 and a leucine at position 338 of SEQ ID NO: 2.

7. The sequence of nucleotides according to claim 6 , wherein the nucleotide sequence has at least 90% homology with the sequence having accession number K02402 (GenBank).

8. A nucleotide sequence encoding a modified FIX (Factor IV) polypeptide comprising 100% identity to SEQ ID NO: 2 except for an alanine at position 148 and a leucine at position 338 of SEQ ID NO: 2 in combination with positions corresponding to positions 34098, 34099 and 34100 of a sequence having accession number K02402 (GenBank) having a triplet selected from the group consisting of: TTA, UUA, TTG, UUG, CTT, CUU, CTC, CUC, CTA, CUA, CTG, and CUG, GAT, GAU and GAC.

9. A nucleic acid comprising the nucleotide sequence according to claim 6 .

10. The nucleic acid according to claim 9 , the nucleic acid comprising a promoter in operational linkage with said nucleotide sequence.

11. A vector comprising the nucleic acid according to claim 9 .

12. A pharmaceutical composition comprising the sequence of nucleotide according to claim 6 .

13. A method for producing a modified FIX (Factor IX) polypeptide, the method comprising

expressing the modified FIX polypeptide by means of a nucleic acid according to claim 9 .

14. A method to perform gene therapy, the method comprising

administering to an individual in need thereof the nucleotide sequence according to claim 6 via a vector configured for gene therapy.

15. The method according to claim 14 , wherein the administering is performed to treat at least one coagulopathy in the individual.

16. The nucleotide sequence of claim 8 , wherein the triplet is selected from the group consisting of CTC and CTG.

17. The nucleotide sequence of claim 8 , wherein the triplet is selected from the group consisting of CUC and CUG.

18. The nucleotide sequence of claim 8 , wherein the triplet is CTC.

19. The nucleotide sequence of claim 8 , wherein the triplet is CTG.

20. The nucleotide sequence of claim 8 , wherein the triplet is CUC.

21. The nucleotide sequence of claim 8 , wherein the triplet is CUG.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 30, 2024
From: SIMIONI, PAOLO
To: UNIQURE BIOPHARMA B.V.
Reel/Frame 066299/0844 →
Priority Claims (2)
IT BO2008A000564 · Sep 15, 2008 · national
IT BO2009A000275 · May 6, 2009 · national
Continuity (1)
Reissue 13063898 · Sep 15, 2009
References Cited (400)
US 4994371A · Davie et al. · 1991 [cited by applicant]
US 5171569A · Anson et al. · 1992 [cited by applicant]
US 5223408A · Goeddel et al. · 1993 [cited by applicant]
US 6046380A · Clark · 2000 [cited by applicant]
US 6227618B1 · Ligon, Sr. et al. · 2001 [cited by applicant]
US 6277618B1 · Kopetzki et al. · 2001 [cited by applicant]
US 6315995B1 · Pinsky et al. · 2001 [cited by applicant]
US 6531298B2 · Stafford et al. · 2003 [cited by applicant]
US 6610906B1 · Kurachi et al. · 2003 [cited by applicant]
US 6759050B1 · Sista et al. · 2004 [cited by applicant]
US 7125841B2 · Sheehan · 2006 [cited by applicant]
US 7341871B2 · Kurachi et al. · 2008 [cited by applicant]
US 7700734B2 · Lin et al. · 2010 [cited by applicant]
US 7888067B2 · Lin et al. · 2011 [cited by applicant]
US 8383388B2 · Oyhenart et al. · 2013 [cited by applicant]
US 8778870B2 · Madison et al. · 2014 [cited by applicant]
US 9249405B2 · Simioni · 2016 [cited by examiner]
US 9982248B2 · Simioni · 2018 [cited by examiner]
US 10465180B2 · Simioni · 2019 [cited by applicant]
US 10888628B2 · Wang et al. · 2021 [cited by applicant]
US 11452749B2 · Nijmeijer et al. · 2022 [cited by applicant]
US 20020031799A1 · Stafford et al. · 2002 [cited by applicant]
US 20020166130A1 · Velander et al. · 2002 [cited by applicant]
US 20040102388A1 · High et al. · 2004 [cited by applicant]
US 20040110675A1 · Sheehan · 2004 [cited by applicant]
US 20040110688A1 · Bajaj et al. · 2004 [cited by applicant]
US 20040133930A1 · Cooper et al. · 2004 [cited by applicant]
US 20040146938A1 · Nguyen et al. · 2004 [cited by applicant]
US 20040254106A1 · Carr et al. · 2004 [cited by applicant]
US 20050100982A1 · DeFrees et al. · 2005 [cited by applicant]
US 20050276787A1 · Couto et al. · 2005 [cited by applicant]
US 20060031956A1 · Kurachi et al. · 2006 [cited by applicant]
US 20060040856A1 · DeFrees et al. · 2006 [cited by applicant]
US 20060188482A1 · Kay et al. · 2006 [cited by applicant]
US 20060292117A1 · Loiler et al. · 2006 [cited by applicant]
US 20070093443A1 · Madison et al. · 2007 [cited by applicant]
US 20070172846A1 · Zhang et al. · 2007 [cited by applicant]
US 20070243526A1 · Kay et al. · 2007 [cited by applicant]
US 20070243615A1 · Qu et al. · 2007 [cited by applicant]
US 20070244036A1 · Scheiflinger et al. · 2007 [cited by applicant]
US 20070274908A1 · Pasqualini et al. · 2007 [cited by applicant]
US 20070280906A1 · Petras · 2007 [cited by applicant]
US 20080003202A1 · Guyon et al. · 2008 [cited by applicant]
US 20080102115A1 · Oyhenart et al. · 2008 [cited by applicant]
US 20080167219A1 · Lin et al. · 2008 [cited by applicant]
US 20080260820A1 · Borrelly et al. · 2008 [cited by applicant]
US 20080305991A1 · DeFrees et al. · 2008 [cited by examiner]
US 20110154516A1 · Stafford et al. · 2011 [cited by applicant]
US 20120164130A1 · Brooks et al. · 2012 [cited by applicant]
US 20150283267A1 · Vandendriessche et al. · 2015 [cited by applicant]
US 20160304851A1 · Schuttrumpf et al. · 2016 [cited by applicant]
US 20160375110A1 · High et al. · 2016 [cited by applicant]
US 20170260516A1 · Tan et al. · 2017 [cited by applicant]
US 20170326256A1 · Doering et al. · 2017 [cited by applicant]
US 20190076550A1 · Wang et al. · 2019 [cited by applicant]
BR 0705943 · 2008 [cited by applicant]
EP 0107278 · 1984 [cited by applicant]
EP 2048236 · 2009 [cited by applicant]
EP 1781782 · 2010 [cited by applicant]
EP 2337849 · 2011 [cited by applicant]
EP 2368983 · 2016 [cited by applicant]
EP 2767587 · 2017 [cited by applicant]
WO 9600577 · 1996 [cited by applicant]
WO WO9903496 · 1999 [cited by examiner]
WO 9949880 · 1999 [cited by applicant]
WO 0170763 · 2001 [cited by applicant]
WO 0204544 · 2002 [cited by applicant]
WO 0240544 · 2002 [cited by applicant]
WO 02096454 · 2002 [cited by applicant]
WO 03020764 · 2003 [cited by applicant]
WO 2006018204 · 2006 [cited by applicant]
WO 2006018201 · 2006 [cited by applicant]
WO 2006031226 · 2006 [cited by applicant]
WO 2006036502 · 2006 [cited by applicant]
WO 2006048777 · 2006 [cited by applicant]
WO 2006066066 · 2006 [cited by applicant]
WO 2007059876 · 2007 [cited by applicant]
WO 2007075976 · 2007 [cited by applicant]
WO 2007089632 · 2007 [cited by applicant]
WO 2007135182 · 2007 [cited by applicant]
WO 2007149406 · 2007 [cited by applicant]
WO 2007149852 · 2007 [cited by applicant]
WO 2008092643 · 2008 [cited by applicant]
WO 2008118507 · 2008 [cited by applicant]
WO 2008119815 · 2008 [cited by applicant]
WO 2008127654 · 2008 [cited by applicant]
WO 2009051717 · 2009 [cited by applicant]
WO 2009130198 · 2009 [cited by applicant]
WO 2009140015 · 2009 [cited by applicant]
WO WO2009137254 · 2009 [cited by examiner]
WO 2010012451 · 2010 [cited by applicant]
WO 2010029178 · 2010 [cited by applicant]
WO 2010151736 · 2010 [cited by applicant]
WO 2011014890 · 2011 [cited by applicant]
WO 2016146757 · 2016 [cited by applicant]
WO 2017024060 · 2017 [cited by applicant]
WO 2020016318 · 2020 [cited by applicant]
Stafford, Thrombosis Journal, 14 (Suppl. 1): 35, pp. 87-91. (Year: 2016). [cited by examiner]
Souid, Pediatric Emergency Medicine, Chapter 130—Disorders of Coagulation, pp. 917-926 (Year: 2008). [cited by examiner]
GenBank Accession No. K02402: Human coagulation Factor IX gene, complete cds, 12 pages (Year: 1996). [cited by examiner]
“Abnormal Uterine Bleeding”, Wikipedia Article, Oct. 14, 2018, 3 pages. [cited by applicant]
“Agreement between Avigen, Inc. and Bayer Corporation”, Form 10-Q Ex-10.43, Feb. 13, 2001, 83 pages. [cited by applicant]
“Annex to Examining Division Summons for Divisional Application EP3252157”, Dec. 17, 2018, 3 pages. [cited by applicant]
“Annual Report Pursuant to Section 13 or 15(D) of the Securities Exchange Act of 1934”, United States Securities and Exchange Commission, Form 20-F, Accessed from Internet on Feb. 23, 2022, 255 pages. [cited by applicant]
“Avigen Dropping AAV Gene Therapy”, LexisNexis, Feb. 22, 2022, 2 pages. [cited by applicant]
“BeneFIX Coagulation Factor IX (Recombinant)”, Hoffmann Eitle, Exhibit No. D16, Mar. 12, 2019, 16 pages. [cited by applicant]
“Cardiovascular Disease”, Wikipedia Article, Feb. 17, 2019, 25 pages. [cited by applicant]
“Current Report Pursuant to Section 13 or 15(D) of the Securities and Exchange Act of 1934”, Avigen, Inc., United States Securities and Exchange Commission, Accessed from Internet on Feb. 23, 2022, 6 pages. [cited by applicant]
“Deposition of Dr. Lili Wang”, Errata Sheet, Sep. 15, 2020, pp. 251-252. [cited by applicant]
“Deposition of Dr. Lili Wang, Ph.D.”, Errata Sheet, Feb. 9, 2021, 5 pages. [cited by applicant]
“Fields Virology”, Knipe & Howley Eds., 5th Edition, 2007, 33 pages. [cited by applicant]
“Freeline Presents Long-Term Follow-Up Data from Phase 1/2 B-Amaze Trial in Hemophilia B at the 2021 ASH Annual Meeting and Announces Early Initiation of Phase 1/2 B-Lieve Dose-Confrmation Trial”, Globe Newswire, Dec. 1… [cited by applicant]
“Guidance for Human Somatic Cell Therapy and Gene Therapy”, U.S. Department of Health and Human Services Food and Drug Administration, Center for Biologics Evaluation and Research, Mar. 1998, 30 pages. [cited by applicant]
“Hematologic Disease”, Wikipedia Article, Dec. 30, 2018, 4 pages. [cited by applicant]
“Hemophilia”, UniQure, Available online at <http://uniqure.com/gene-therapy/hemophilia.php>, Accessed from Internet on: Jan. 9, 2021, 4 pages. [cited by applicant]
“Human Coagulation Factor IX Gene, Complete Cds”, GenBank Reference Sequence: K02402.1, Apr. 30, 1996, 12 pages. [cited by applicant]
“Human Gene Therapy for Hemophilia, Guidance for Industry”, U.S. Depart of Health and Human Services, Food and Drugs Administration, 2020, 17 pages. [cited by applicant]
“Hydrophobicity Scales”, Rockefeller University, Available Online at: http://web.archive.org/web/20200222103717/http://prowl.rockefell er.edu/aainfo/hydro.htm, Feb. 22, 2020, 2 pages. [cited by applicant]
“Investigational Medicinal Product Dossier”, AAV5-hFIXco-Padua, Version 4.0, (IMPD) (redacted), Oct. 24, 2019, 14 pages. [cited by applicant]
“Investigator's Brochure (IB)”, AAV5-hFIXco and AAV-hFIXco-Padua, Version 1.0, (IB) (redacted), Feb. 13, 2020, 46 pages. [cited by applicant]
“IPR2020-00388”, Coagulation cascade drawing by Dr. Lili Wang, Sep. 15, 2020, 1 page. [cited by applicant]
“IPR2020-00388”, Affidavit of Elizabeth Rosenberg, Gao PDF Version, Aug. 7, 2020, 10 pages. [cited by applicant]
“IPR2020-00388”, Declaration of Lili Wang, Exhibit 1003 of Petition for Inter Partes review of U.S. Pat. No. 9,249,405, Jan. 3, 2020, 105 pages. [cited by applicant]
“IPR2020-00388”, Affidavit of Duncan Hall, submitted as Exhibit 1093, Jan. 11, 2021, 11 pages. [cited by applicant]
“IPR2020-00388”, Affidavit of Elizabeth Rosenberg, Schuettrumpf TOC, Aug. 7, 2020, 12 pages. [cited by applicant]
“IPR2020-00388”, Patent Owners Objections to Petition Evidence, Jul. 27, 2020, 12 pages. [cited by applicant]
“IPR2020-00388”, Affidavit of Rachel J. Watters, Aug. 6, 2020, 13 pages. [cited by applicant]
“IPR2020-00388”, Declaration of Rachel J. Watters, Submitted as Exhibit 1086, Jan. 7, 2021, 14 pages. [cited by applicant]
“IPR2020-00388”, Declaration of Lili Wang, Exhibit 1003 of Petition for Inter Partes review of U.S. Pat. No. 9,249,405, Jan. 13, 2021, 146 pages. [cited by applicant]
“IPR2020-00388”, Revised Declaration of Dr. Christopher Doering, Dec. 2, 2020, 149 pages. [cited by applicant]
“IPR2020-00388”, Declaration of Dr. Christopher Doering, Oct. 13, 2020, 149 pages. [cited by applicant]
“IPR2020-00388”, Affidavit of Elizabeth Rosenberg, Gao TOC, Aug. 7, 2020, 15 pages. [cited by applicant]
“IPR2020-00388”, Declaration of Star Andrews, Aug. 8, 2020, 15 pages. [cited by applicant]
“IPR2020-00388”, Affidavit of Elizabeth Rosenberg, Gao HTML Version, Aug. 7, 2020, 16 pages. [cited by applicant]
“IPR2020-00388”, Preliminary Guidance, Patent Owner's Motion to Amend, Feb. 3, 2021, 16 pages. [cited by applicant]
“IPR2020-00388”, Definition of Individual at Dictionary.com, Apr. 15, 2020, 2 pages. [cited by applicant]
“IPR2020-00388”, Transcript of Telephonic Hearing held, Feb. 23, 2021, 20 pages. [cited by applicant]
“IPR2020-00388”, Transcript of Teleconference, Oct. 1, 2020, 25 pages. [cited by applicant]
“IPR2020-00388”, Affidavit of Elizabeth Rosenberg, Schuettrumpf HTML Version, Aug. 7, 2020, 27 pages. [cited by applicant]
“IPR2020-00388”, Declaration of James L. Mullins, Ph.D., Aug. 10, 2020, 280 pages. [cited by applicant]
“IPR2020-00388”, Deposition of Lili Wang, Feb. 9, 2021, 293 pages. [cited by applicant]
“IPR2020-00388”, Email from Patent and Trial Appeal Board to Dov Grossman and Justin Krieger, submitted as Exhibit 2069, Mar. 3, 2021, 3 pages. [cited by applicant]
“IPR2020-00388”, Patent Owner's Notice of Withdrawal of Motion to Amend, Mar. 4, 2021, 3 pages. [cited by applicant]
“IPR2020-00388”, Affidavit of Duncan Hall, submitted as Exhibit 1084, Jan. 11, 2021, 32 pages. [cited by applicant]
“IPR2020-00388”, Decision Granting Institution of Inter Partes Review, Jul. 13, 2020, 32 pages. [cited by applicant]
“IPR2020-00388”, Deposition of Lee Pedersen, Sep. 17, 2020, 321 pages. [cited by applicant]
“IPR2020-00388”, Deposition of Lili Wang, Sep. 15, 2020, 330 pages. [cited by applicant]
“IPR2020-00388”, Patent Owner's Revised Non-Contingent Motion to Amend, Dec. 2, 2020, 34 pages. [cited by applicant]
“IPR2020-00388”, Patent Owners Non-Contingent Motion to Amend, Oct. 13, 2020, 34 pages. [cited by applicant]
“IPR2020-00388”, Petitioner's Opoosition to Patent Owner's Revised Non-Contingent Motion to Amend, Jan. 13, 2021, 35 pages. [cited by applicant]
“IPR2020-00388”, Deposition Transcript of Dr. Christopher Doering, Dec. 3, 2020, 355 pages. [cited by applicant]
“IPR2020-00388”, Disclaimer of Claims 6 and 9-13 in U.S. Pat. No. 9,249,405, Apr. 16, 2020, 4 pages. [cited by applicant]
“IPR2020-00388”, Revised Declaration of Elizabeth Heijink redacted, Dec. 7, 2020, 4 pages. [cited by applicant]
“IPR2020-00388”, Patent Owner's Motion to Terminate Proceeding, Mar. 4, 2021, 4 pages. [cited by applicant]
“IPR2020-00388”, Transcript of Telephonic Meeting, Nov. 24, 2020, 43 pages. [cited by applicant]
“IPR2020-00388”, Declaration of James L. Mullins, Ph.D. re: EX1017, EX1083, and EX1082, Jan. 13, 2021, 472 pages. [cited by applicant]
“IPR2020-00388”, Affidavit of Elizabeth Rosenberg, Hasbrouck Online TOC, Aug. 7, 2020, 5 pages. [cited by applicant]
“IPR2020-00388”, Affidavit of Elizabeth Rosenberg, Schuettrumpf PDF, Aug. 7, 2020, 5 pages. [cited by applicant]
“IPR2020-00388”, Email from Justin Krieger to Patent Trial and Appeal Board, Exhibit 1094, Mar. 5, 2021, 5 pages. [cited by applicant]
“IPR2020-00388”, Order Conduct of the Proceeding, Oct. 2, 2020, 5 pages. [cited by applicant]
“IPR2020-00388”, Patent Owner Preliminary Response, Apr. 17, 2020, 51 pages. [cited by applicant]
“IPR2020-00388”, Selected File History of U.S. Pat. No. 10,465,180, as Exhibit 2014, Apr. 17, 2020, 51 pages. [cited by applicant]
“IPR2020-00388”, Deposition Transcript of Dr. Elizabeth Heijink (Dec. 10, 2020) (Redacted), 2020, 6 pages. [cited by applicant]
“IPR2020-00388”, submitted as Exhibit 2070, Disclaimer in Patent under 37 C.F.R. 1.321(a), Mar. 4, 2021, 6 pages. [cited by applicant]
“IPR2020-00388”, Order Conduct of the Proceeding, Nov. 27, 2020, 6 pages. [cited by applicant]
“IPR2020-00388”, Declaration of Elisabeth Heijink, Oct. 13, 2020, 6 pages. [cited by applicant]
“IPR2020-00388”, Patent Examination Policy—MPEP Staff—35 USC 112 1st Para—Enablement of Chemical/Biotechnical Applications, Apr. 17, 2020, 71 pages. [cited by applicant]
“IPR2020-00388”, Declaration of Lee Pedersen, Ph.D., executed Jan. 3, 2020, Exhibit 1002 of Petition for Inter Partes review of U.S. Pat. No. 9,249,405, Jan. 3, 2020, 73 pages. [cited by applicant]
“IPR2020-00388”, Petition for Inter Partes Review of U.S. Pat. No. 9,249,405, Jan. 4, 2020, 75 pages. [cited by applicant]
“IPR2020-00388”, Affidavit of Elizabeth Rosenberg, Advanced Online Publication of Hasbrouck, Aug. 7, 2020, 9 pages. [cited by applicant]
“IPR2020-00388”, Petitioner's Opposition to Patent Owner's Motion to Terminate, Mar. 16, 2021, 9 pages. [cited by applicant]
“IPR2021-00925”, Patent Owner's Response to Petitioner's Notice Regarding Multiple Petitions in IPR2021-00925 and IPR2021-00926, Aug. 21, 2021, 8 pages. [cited by applicant]
“IPR2021-00925”, Patent Owner Preliminary Response, Aug. 21, 2021, 80 pages. [cited by applicant]
“IPR2021-00925”, Patent Owner Preliminary Response, Aug. 23, 2021, 80 pages. [cited by applicant]
“IPR2021-00926”, Patent Owner's Response to Petitioner's Notice Regarding Multiple Petitions in IPR2021-00925 and IPR2021-00926, Aug. 21, 2021, 8 pages. [cited by applicant]
“IPR2021-00926”, Patent Owner Preliminary Response, Aug. 21, 2021, 80 pages. [cited by applicant]
“IPR2021-00926”, Patent Owner Preliminary Response, Aug. 23, 2021, 80 pages. [cited by applicant]
“IPR2021-00928”, Email from Patent and Trial Appeal Board to Dov Grossman, (Exhibit 2087), Jul. 21, 2021, 2 pages. [cited by applicant]
“IPR2021-00928”, Third Party Submission, File History of U.S. Pat. No. 10,465,180, (Exhibit 2080), Mar. 14, 2019, 25 pages. [cited by applicant]
“IPR2021-00928”, Information Disclosure Statement, File History for U.S. Pat. No. 9,249,405, (Exhibit 2010), Mar. 31, 2014, 3 pages. [cited by applicant]
“IPR2021-00928”, Patent Owner Preliminary Response, Aug. 24, 2021, 83 pages. [cited by applicant]
“Long-Acting Factor Vlla had Longer Duration of Action in Hemophilic A Mice”, ISTH 2009 Daily, XXII Congress International Society on Thrombosis and Haemostasis, 2009, 12 pages. [cited by applicant]
“National Case Law on Peer Reviewed Documents”, Jan. 23, 2019, 2 pages. [cited by applicant]
“ [cited by applicant]
“Pfizer Initiates Pivotal Phase 3 Program for Investigational Hemophilia B Gene Therapy”, Spark Therapeutics Press Release, Available online at https://sparktx.com/press_releases/pfizer-initiates-pivotal-phase-3-program… [cited by applicant]
“Press Release: Spark Therapeutics to Present with Pfizer Inc. Preclinical Data on Their Lead SPK-FIX Product Candidate for Hemophilia B at the 2015 International Society of Thrombosis and Haemostasis Congress in June”,… [cited by applicant]
“STN—The Choice of Patent Experts”, CAS Registry Fact Sheet, 2014, 1 page. [cited by applicant]
“Supplementary Table 1. Inclusion/exclusion Criteria”, Supplementary Data, uniQure 2128, 2006, 1 page. [cited by applicant]
“Textbook of Hemophilia”, Third Edition, 2014, 25 pages. [cited by applicant]
“The Value of Treatment Advances in Hemophilia”, Pfizer, Value of Medicine, Available Online at: https://cdn.pfizer.com/pfizercom/health/VoM, Dec. 2016, 5 pages. [cited by applicant]
“UniQure Announces Achievement of Target Patient Dosing in HOPE-B Pivotal Trial of AMT-061 (Etranacogene Dezaparvovec) in Hemophilia B”, UniQure, Available Online at: https:piplelinereview.com/index.php/2020032774138/DN… [cited by applicant]
“UniQure Announces FDA Removes Clinical Hold on Hemophilia B Gene Therapy Program”, UniQure Press Release, Available online at : https://tools.eurolandir.com/tools/Pressreleases/GetPressRelease/?ID=3902770&lang=en-GB&co… [cited by applicant]
“Uniqure Announces First Patient Treated in Pivotal Trial”, UniQure, Available Online at: https://drug-dev.com/uniqure-announces-first-patient-treated-in-pivotal-trial/, Oct. 13, 2020, 34 pages. [cited by applicant]
“What is Gene Therapy?”, U.S. Food & Drug Admin, Available Online at: https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/what-gene-therapy, Accessed from Internet on Jan. 9, 2021, 2 pages. [cited by applicant]
Court File No. T-2118-22, Between Pfizer Canada ULC and Pfizer Inc. and Uniqure BioPharma B.V., Written Representations of the Plaintiffs (Defendant's Motion for a Stay), Before the Federal Court, Mar. 23, 2023, 28 page… [cited by applicant]
U.S. Appl. No. 13/063,898 , “Final Office Action”, Dec. 31, 2014, 21 pages. [cited by applicant]
U.S. Appl. No. 13/063,898 , “Non-Final Office Action”, Apr. 3, 2014, 14 pages. [cited by applicant]
U.S. Appl. No. 13/063,898 , “Notice of Allowance”, Nov. 12, 2015, 4 pages. [cited by applicant]
U.S. Appl. No. 13/063,898 , “Notice of Allowance”, Sep. 28, 2015, 7 pages. [cited by applicant]
U.S. Appl. No. 14/981,981 , “Non-Final Office Action”, Dec. 7, 2017, 13 pages. [cited by applicant]
U.S. Appl. No. 15/650,070 , “Non-Final Office Action”, Dec. 15, 2017, 15 pages. [cited by applicant]
U.S. Appl. No. 15/650,070 , “Notice of Allowance”, Apr. 10, 2018, 5 pages. [cited by applicant]
U.S. Appl. No. 15/989,665 , “Non-Final Office Action”, Apr. 8, 2019, 7 pages. [cited by applicant]
U.S. Appl. No. 15/989,665 , “Notice of Allowance”, Oct. 7, 2019, 2 pages. [cited by applicant]
U.S. Appl. No. 15/989,665 , “Notice of Allowance”, Jul. 31, 2019, 5 pages. [cited by applicant]
U.S. Appl. No. 16/589,851 , “Non-Final Office Action”, Dec. 20, 2021, 23 pages. [cited by applicant]
U.S. Appl. No. 16/707,414 , “Non-Final Office Action”, Mar. 11, 2021, 16 pages. [cited by applicant]
U.S. Appl. No. 16/787,456 , “Non-Final Office Action”, Jul. 8, 2021, 19 pages. [cited by applicant]
U.S. Appl. No. 17/213,848 , “Advisory Action”, Dec. 21, 2021, 9 pages. [cited by applicant]
U.S. Appl. No. 17/213,848 , “Final Office Action”, Sep. 13, 2021, 18 pages. [cited by applicant]
U.S. Appl. No. 17/213,848 , “Non-Final Office Action”, Jul. 7, 2022, 12 pages. [cited by applicant]
U.S. Appl. No. 17/213,848 , “Non-Final Office Action”, May 28, 2021, 16 pages. [cited by applicant]
U.S. Appl. No. 17/213,897 , “Advisory Action”, Dec. 21, 2021, 6 pages. [cited by applicant]
U.S. Appl. No. 17/213,897 , “Final Office Action”, Sep. 14, 2021, 19 pages. [cited by applicant]
U.S. Appl. No. 17/213,897 , “Non-Final Office Action”, Jun. 1, 2021, 18 pages. [cited by applicant]
U.S. Appl. No. 17/213,897 , “Non-Final Office Action”, Jul. 12, 2022, 23 pages. [cited by applicant]
U.S. Appl. No. 17/447,372 , “Non-Final Office Action”, Jun. 21, 2023, 31 pages. [cited by applicant]
U.S. Appl. No. 17/643,326 , “Non-Final Office Action”, May 15, 2023, 18 pages. [cited by applicant]
U.S. Appl. No. 60/999,035 , “U.S. Provisional Patent Application No.”, Human Factory IX Variants With an Extended Half Life, Oct. 15, 2007, 42 pages. [cited by applicant]
Ahmad et al., “The Role of the First Growth Factor Domain of Human Factor IXa in Binding to Platelets and in Factor X Activation”, The Journal of Biological Chemistry, vol. 267, No. 12, Apr. 25, 1992, pp. 8571-8576. [cited by applicant]
Altschul et al., “Basic Local Alignment Search Tool”, Journal of Molecular Biology, vol. 215, No. 3, Oct. 5, 1990, pp. 403-410. [cited by applicant]
Altschul et al., “Gapped Blast and PSI-Blast: A New Generation of Protein Database Search Programs”, Nucleic Acids Research, vol. 25, No. 17, Sep. 1, 1997, pp. 3389-3402. [cited by applicant]
Ameri et al., “Myocardial Fibrosis in Mice with Over-Expression of Human Blood Coagulation Factor IX”, Blood, vol. 101, No. 5, Apr. 2003, 10 pages. [cited by applicant]
Anson et al., “The Gene Structure of Human Anti-Haemophilic Factor IX”, The EMBO Journal, vol. 3, No. 5, May 1984, pp. 1053-1060. [cited by applicant]
Armentano et al., “Expression of Human Factor IX in Rabbit Hepatocytes by Retrovirus-Mediated Gene Transfer: Potential for Gene Therapy of Hemophilia B”, Proceedings of the National Academy of Sciences of the United Sta… [cited by applicant]
Armstrong , “UniQure Turns the Screw on Spark and Pfizer”, Evaluate Vantage, Feb. 2019, 2 pages. [cited by applicant]
Aucoin et al., “Critical Assessment of Current Adeno-Associated Viral Vector Production and Quantification Methods”, Biotechnology Advances, vol. 26, No. 1, Jan.-Feb. 2008, pp. 73-88. [cited by applicant]
Bajaj et al., “Factor IXa: Factor Villa Interaction. Helix 330-338 of Factor Ixa Interacts with Residues 558-565 and Spatially Adjacent Regions of the a2 Subunit of Factor Villa”, The Journal of Biological Chemistry, vo… [cited by applicant]
Bassett et al., “Recent Developments in Hemophilia: Gene Therapy”, MedPage Today, Available Online At https://www.medpagetoday.com/recent-developments/hemophilia/78500, Mar. 11, 2019, 5 pages. [cited by applicant]
Benefix , “Coagulation Factor IX (Recombinant) label”, 2006, 2 pages. [cited by applicant]
Betts et al., “Amino Acid Properties and Consequences of Substitutions”, Bioinformatics for Geneticists, Feb. 21, 2003, 28 pages. [cited by applicant]
Bezemer et al., “F9 Malmo, Factor IX And Deep Vein Thrombosis”, Haematologica, vol. 94, No. 5, May 2009, pp. 693-699. [cited by applicant]
Bond et al., “Biochemical Characterization of Recombinant Factor IX”, Seminars in Hematology, vol. 35, No. 2, 1998, pp. 11-17. [cited by applicant]
Bottema et al., “The Pattern of Spontaneous Germ-Line Mutation: Relative Rates of Mutation at or Near CpG Dinucleotides in the Factor IX Gene”, Human Genetics, vol. 91, No. 5, Jun. 1993, pp. 496-503. [cited by applicant]
Bowen , “Haemophilia A and Haemophilia B: Molecular Insights”, Molecular Pathology, vol. 55, No. 2, 2002, pp. 127-144. [cited by applicant]
Bowie et al., “Deciphering the Message in Protein Sequences: Tolerance to Amino Acid Substitutions”, Science, vol. 247, No. 4948, Mar. 16, 1990, pp. 1306-1310. [cited by applicant]
Branca , “Gene Therapy: Cursed or Inching Towards Credibility?”, Nature Biotechnology, vol. 23, No. 5, May 2005, pp. 519-521. [cited by applicant]
Branden et al., “Introduction to Protein Structure”, Garland Publishing, 2012, 73 pages. [cited by applicant]
Brandstetter et al., “X-Ray Structure of Clotting Factor IXa: Active Site and Module Structure Related to Xase Activity and Hemophilia B”, Proceedings of the National Academy of Sciences, vol. 92, No. 21, Oct. 10, 1995,… [cited by applicant]
Brickhous et al., “Recombinant Human Factor IX: Replacement Therapy, Prophylaxis, and Pharmacokinetics in Canine Hemophilia B”, Blood, vol. 88, No. 7, Oct. 1, 1996, pp. 2603-2610. [cited by applicant]
Brown et al., “Development of a Clinical Candidate AAV3 Vector for Gene Therapy of Hemophilia B”, Human Gene Therapy, vol. 31, Nos. 19-20, Oct. 2020, pp. 1114-1123. [cited by applicant]
Brownlee , “The Molecular Genetics of Haemophilia A and B”, Journal of Cell Science, No. 4, 1986, pp. 445-458. [cited by applicant]
Brunetti-Pierri et al., “Bioengineered Factor IX Molecules with Increased Catalytic Activity Improve the Therapeutic Index of Gene Therapy Vectors for Hemophilia B”, Human Gene Therapy, vol. 20, No. 5, May 2009, pp. 479… [cited by applicant]
Bueler , “Adeno-Associated Viral Vectors for Gene Transfer and Gene Therapy”, Journal of Biological Chemistry, vol. 380, No. 6, Jun. 1999, pp. 613-622. [cited by applicant]
Cancio et al., “Developments in the Treatment of Hemophilia B: Focus on Emerging Gene Therapy”, The Application of Clinical Genetics, vol. 6, 2013, pp. 91-101. [cited by applicant]
Cantore et al., “Hyperfunctional Coagulation Factor IX Improves the Efficacy of Gene Therapy in Hemophilic Mice”, Blood, vol. 120, No. 23, Nov. 29, 2012, pp. 4517-4520. [cited by applicant]
Case IPR2021-00925 , “Declaration of Cindy Kan in Support of Exhibits 2025, 2075, 2076, 2088”, Before the Patent Trial and Appeal Board, Dec. 16, 2021, 5 pages. [cited by applicant]
Case IPR2021-00925 , “Declaration of Dr. Christopher Doering Under 37 C.f.r. § 1.68”, Before the Patent Trial and Appeal Board, Mar. 3, 2022, 403 pages. [cited by applicant]
Case IPR2021-00925 , “Declaration of James M. Lyons in Support of Motion for Admission Pro Hac Vice”, Before the Patent Trial and Appeal Board, Dec. 20, 2021, 4 pages. [cited by applicant]
Case IPR2021-00925 , “Declaration of Joshua L. Stern in Support of Motion for Admission Pro Hac Vice”, Before the Patent Trial and Appeal Board, Dec. 20, 2021, 4 pages. [cited by applicant]
Case IPR2021-00925 , “Declaration of P. Clint Spiegel, Ph.D.”, Before the Patent Trial and Appeal Board, Mar. 3, 2022, 100 pages. [cited by applicant]
Case IPR2021-00925 , “Deposition of Lee Grant Pedersen, Ph.D. Conducted Virtually”, Planet Depos, Before the Patent Trial and Appeal Board, Feb. 22, 2022, 141 pages. [cited by applicant]
Case IPR2021-00925 , “Final Written Decision Determining All Challenged Claims Unpatentable 35 U.S.C. § 318(a)”, Before the Patent Trial and Appeal Board, Nov. 15, 2022, 50 pages. [cited by applicant]
Case IPR2021-00925 , “Notice of Joint Stipulation to Modify the Scheduling Order”, Before the Patent Trial and Appeal Board, Dec. 22, 2021, 4 pages. [cited by applicant]
Case IPR2021-00925 , “Patent Owner's Motion for Admission Pro Hac Vice of James M. Lyons”, Before the Patent Trial and Appeal Board, Dec. 20, 2021, 12 pages. [cited by applicant]
Case IPR2021-00925 , “Patent Owner's Motion for Admission Pro Hac Vice of Joshua L. Stern”, Before the Patent Trial and Appeal Board, Dec. 20, 2021, 12 pages. [cited by applicant]
Case IPR2021-00925 , “Patent Owner's Notice of Deposition of Lee Pedersen, Ph.D.”, Before the Patent Trial and Appeal Board, Feb. 2, 2022, 3 pages. [cited by applicant]
Case IPR2021-00925 , “Patent Owner's Notice of Deposition of Lili Wang, Ph.D.”, Before the Patent Trial and Appeal Board, Feb. 2, 2022, 3 pages. [cited by applicant]
Case IPR2021-00925 , “Patent Owner's Objections to Evidence Pursuant to 37 CFR 42.64”, Before the Patent Trial and Appeal Board, Dec. 2, 2021, 14 pages. [cited by applicant]
Case IPR2021-00925 , “Patent Owner's Second Update to Mandatory Notices Under 37 C.F.R. § 42.8”, Before the Patent Trial and Appeal Board, Dec. 20, 2021, 5 pages. [cited by applicant]
Case IPR2021-00925 , “Petitioner's Motion to Submit Supplemental Information Pursuant to 37 C.f.r § 42.123(A)”, Before the Patent Trial and Appeal Board, Jan. 6, 2022, 8 pages. [cited by applicant]
Case IPR2021-00925 , “Petitioner's Objections to Evidence”, Before the Patent Trial and Appeal Board, Mar. 10, 2022, 28 pages. [cited by applicant]
Case IPR2021-00925 , “Petitioner's Objections to Patent Owner's Preliminary Response Evidence”, Before the Patent Trial and Appeal Board, Dec. 2, 2021, 12 pages. [cited by applicant]
Case IPR2021-00925 , “Transcript of Lili Wang, Ph.D.”, Planet Depos, Before the Patent Trial and Appeal Board, Feb. 16, 2022, 191 pages. [cited by applicant]
Case IPR2021-00925 , “Videotaped Videoconference Deposition of Lee Pedersen, Ph.D.”, Before the Patent Trial and Appeal Board, Sep. 17, 2020, 321 pages. [cited by applicant]
Case IPR2021-00926 , “Final Written Decision Determining All Challenged Claims Unpatentable 35 U.S.C. § 318(a)”, Before the Patent Trial and Appeal Board, Nov. 15, 2022, 60 pages. [cited by applicant]
Case IPR2021-00926 , “Notice of Joint Stipulation to Modify the Scheduling Order”, Before the Patent Trial and Appeal Board, Dec. 22, 2021, 4 pages. [cited by applicant]
Case IPR2021-00926 , “Patent Owner Response”, Before the Patent Trial and Appeal Board, Mar. 3, 2022, 89 pages. [cited by applicant]
Case IPR2021-00926 , “Patent Owner's Motion for Admission Pro Hac Vice of James M. Lyons”, Before the Patent Trial and Appeal Board, Dec. 20, 2021, 12 pages. [cited by applicant]
Case IPR2021-00926 , “Patent Owner's Motion for Admission Pro Hac Vice of Joshua L. Stern”, Before the Patent Trial and Appeal Board, Dec. 20, 2021, 13 pages. [cited by applicant]
Case IPR2021-00926 , “Patent Owner's Notice of Deposition of Lee Pedersen, PH.D.”, Before the Patent Trial and Appeal Board, Feb. 2, 2022, 3 pages. [cited by applicant]
Case IPR2021-00926 , “Patent Owner's Notice of Deposition of Lili Wang, PH.D.”, Before the Patent Trial and Appeal Board, Feb. 2, 2022, 3 pages. [cited by applicant]
Case IPR2021-00926 , “Patent Owner's Objections to Evidence Pursuant to 37 C.F.R. § 42.64”, Before the Patent Trial and Appeal Board, Dec. 2, 2021, 13 pages. [cited by applicant]
Case IPR2021-00926 , “Patent Owner's Second Update to Mandatory Notices Under 37 C.F.R. § 42.8”, Before the Patent Trial and Appeal Board, Dec. 20, 2021, 5 pages. [cited by applicant]
Case IPR2021-00926 , “Petitioner's Motion to Submit Supplemental Information Pursuant to 37 C.F.R § 42.123(a)”, Before the Patent Trial and Appeal Board, Jan. 6, 2022, 8 pages. [cited by applicant]
Case IPR2021-00926 , “Petitioner's Objections to Evidence”, Before the Patent Trial and Appeal Board, Mar. 10, 2022, 28 pages. [cited by applicant]
Case IPR2021-00926 , “Petitioner's Objections to Patent Owner's Preliminary Response Evidence”, Before the Patent Trial and Appeal Board, Dec. 2, 2021, 11 pages. [cited by applicant]
Case IPR2021-00928 , “Final Written Decision Determining All Challenged Claims Unpatentable 35 U.S.C. § 318(a)”, Before the Patent Trial and Appeal Board, Nov. 15, 2022, 50 pages. [cited by applicant]
Case IPR2021-00928 , “Notice of Joint Stipulation to Modify the Scheduling Order”, Before the Patent Trial and Appeal Board, Dec. 22, 2021, 4 pages. [cited by applicant]
Case IPR2021-00928 , “Patent Owner Response”, Before the Patent Trial and Appeal Board, Mar. 3, 2022, 85 pages. [cited by applicant]
Case IPR2021-00928 , “Patent Owner's Motion for Admission Pro Hac Vice of James M. Lyons”, Before the Patent Trial and Appeal Board, Dec. 20, 2021, 12 pages. [cited by applicant]
Case IPR2021-00928 , “Patent Owner's Motion for Admission Pro Hac Vice of Joshua L. Stern”, Before the Patent Trial and Appeal Board, Dec. 20, 2021, 13 pages. [cited by applicant]
Case IPR2021-00928 , “Patent Owner's Notice of Deposition of Lee Pedersen, PH.D.”, Before the Patent Trial and Appeal Board, Feb. 2, 2022, 3 pages. [cited by applicant]
Case IPR2021-00928 , “Patent Owner's Notice of Deposition of Lili Wang, PH.D.”, Before the Patent Trial and Appeal Board, Feb. 2, 2022, 3 pages. [cited by applicant]
Case IPR2021-00928 , “Patent Owner's Objections to Evidence Pursuant to 37 C.F.R. § 42.64”, Before the Patent Trial and Appeal Board, Dec. 2, 2021, 13 pages. [cited by applicant]
Case IPR2021-00928 , “Patent Owner's Second Update to Mandatory Notices Under 37 C.F.R. § 42.8”, Before the Patent Trial and Appeal Board, Dec. 20, 2021, 5 pages. [cited by applicant]
Case IPR2021-00928 , “Petitioner's Motion to Submit Supplemental Information Pursuant to 37 C.F.R § 42.123(a)”, Before the Patent Trial and Appeal Board, Jan. 6, 2022, 8 pages. [cited by applicant]
Case IPR2021-00928 , “Petitioner's Objections to Evidence”, Before the Patent Trial and Appeal Board, Mar. 10, 2022, 28 pages. [cited by applicant]
Case IPR2021-00928 , “Petitioner's Objections to Patent Owner's Preliminary Response Evidence”, Before the Patent Trial and Appeal Board, Dec. 2, 2021, 12 pages. [cited by applicant]
Chamberlain , “Acute Hemorrhagic Gastritis”, Gastroenterol Clinics of North America, vol. 22, No. 4, Dec. 1993, pp. 843-873. [cited by applicant]
Chang et al., “Changing Residue 338 in Human Factor IX from Arginine to Alanine Causes an Increase in Catalytic Activity”, The Journal of Biological Chemistry, vol. 273, No. 20, May 15, 1998, pp. 12089-12094. [cited by applicant]
Chang et al., “Identification of Functionally Important Residues of the Epidermal Growth Factor-2 Domain of Factor IX by Alanine-Scanning Mutagenesis Residues ASN89-GLY93 are Critical for Binding Factor VIIIa”, Journal … [cited by applicant]
Chang et al., “Residues 330-338 in Catalytic Domain of Factor IX Represent an Interactive Site for Both Factor VIIIa and Factor X”, Blood, Abstract #744, The American Society of Hematology Fortieth Annual Meeting, 1998. [cited by applicant]
Cheung et al., “The Binding of Human Factor IX to Endothelial Cells Is Mediated by Residues 3-11”, The Journal of Biological Chemistry, vol. 267, No. 29, Oct. 15, 1992, pp. 20529-20531. [cited by applicant]
Choi et al., “Production of Recombinant Adeno-Associated Viral Vectors for In Vitro and In Vivo Use”, Current Protocols in Molecular Biology, vol. 16, Issue 25, Apr. 2007, pp. 1-25. [cited by applicant]
Cooley et al., “Dysfunctional Endogenous Fix Impairs Prophylaxis in a Mouse Hemophilia B Model”, Blood, vol. 133, No. 22, May 30, 2019, pp. 2445-2451. [cited by applicant]
Cooley et al., “Prophylactic Efficacy of BeneFIX vs Alprolix in Hemophilia B Mice”, Blood, vol. 128, No. 2, Jul. 14, 2016, pp. 286-292. [cited by applicant]
Coppens et al., “Adults with Haemophilia B Receiving Etranacogene Dezaparvovec in the Hope-B Phase 3 Trial Experience a Stable Increase in Mean Factor IX Activity and Durable Haemostatic Protection after 24 Months' Foll… [cited by applicant]
Couzin et al., “As Gelsinger Case Ends, Gene Therapy Suffers Another Blow”, Science, vol. 307, No. 5712, Feb. 18, 2005, 2 pages. [cited by applicant]
Crick, “The Origin of the Genetic Code”, Journal of Molecular Biology , vol. 38, No. 3, Dec. 28, 1968, pp. 367-379. [cited by applicant]
Crystal , “Adenovirus: The First Effective in Vivo Gene Delivery Vector”, Human Gene Therapy, vol. 25, No. 1, Jan. 2014, pp. 3-11. [cited by applicant]
Dale et al., “From Genes to Genomes: Concepts and Applications of DNA Technology”, John Wiley & Sons, 2011, 94 pages. [cited by applicant]
Davidoff et al., “Purification of Recombinant Adeno-Associated Virus Type 8 Vectors by Ion Exchange Chromatography Generates Clinical Grade Vector Stock”, Journal of Virological Methods, vol. 121, No. 2, Nov. 2004, pp. … [cited by applicant]
Davie et al., “The Coagulation Cascade: Initiation, Maintenance, and Regulation”, Biochemistry, vol. 30, No. 43, Oct. 1991, pp. 10363-10370. [cited by applicant]
Daya et al., “Gene Therapy Using Adeno-Associated Virus Vectors”, Clinical Microbiology Reviews, vol. 21, No. 4, Oct. 2008, pp. 583-593. [cited by applicant]
Dayhoff et al., “A Model of Evolutionary Change in Proteins”, Atlas of Protein Sequence and Structure, vol. 5, 1978, pp. 345-352. [cited by applicant]
Devereux et al., “A Comprehensive Set of Sequence Analysis Programs for the VAX”, Nucleic Acids Research, vol. 12, No. 1, Jan. 11, 1984, pp. 387-395. [cited by applicant]
Driscoll et al., “A Codon 338 Nonsense Mutation in the Factor IX Gene in Unrelated Hemophilia B Patients: Factor IX338 New York”, Blood, vol. 74, No. 2, Sep. 1989, pp. 737-742. [cited by applicant]
Enayat et al., “Mutation Analysis in F9 Gene of 17 Families with Haemophilia B from Iran”, Haemophilia, vol. 10, No. 6, Nov. 2004, pp. 751-755. [cited by applicant]
EP09748260.8 , “Decision Revoking the European Patent”, Mar. 17, 2021, 2 pages. [cited by applicant]
EP09748260.8 , “Declaration by Dr Tagariello”, Dec. 17, 2018, 1 page. [cited by applicant]
EP09748260.8 , “EPO Submission by the Patentee”, May 10, 2016, 10 pages. [cited by applicant]
EP09748260.8 , “EPO Submission by the Patentee”, May 31, 2017, 11 pages. [cited by applicant]
EP09748260.8 , “Letter from Patentee”, Sep. 21, 2015, 12 pages. [cited by applicant]
EP09748260.8 , “Notice of Opposition—Baxalta GmbH”, Mar. 12, 2019, 56 pages. [cited by applicant]
EP09748260.8 , “Notice of Opposition—Greaves Brewster LLP”, Mar. 13, 2019, 12 pages. [cited by applicant]
EP09748260.8 , “Notice of Opposition—Pfizer Inc.”, Mar. 12, 2019, 25 pages. [cited by applicant]
EP09748260.8 , “Notice of Opposition—Strawman Limited”, Dec. 17, 2018, 30 pages. [cited by applicant]
EP09748260.8 , “Notice of Opposition—Weinzierl Gerhard Dr.”, Mar. 12, 2019, 26 pages. [cited by applicant]
EP09748260.8 , “Office Action”, Dec. 14, 2015, 4 pages. [cited by applicant]
EP09748260.8 , “Office Action”, Jan. 26, 2017, 4 pages. [cited by applicant]
EP09748260.8 , “Preliminary Opinion”, Oct. 17, 2019, 12 pages. [cited by applicant]
EP09748260.8 , “Sequence Alignment”, (D12 Opposition Procedure), Feb. 22, 2018, 1 page. [cited by applicant]
EP09748260.8 , “Sequence Alignment”, (D23 Opposition Procedure), Feb. 22, 2018, 1 page. [cited by applicant]
EP09748260.8 , “Response to Summons to Attend Oral Proceedings—Weinzierl Gerhard Dr.”, Apr. 14, 2020, 13 pages. [cited by applicant]
EP09748260.8 , “Summons to Attend Oral Proceedings”, Oct. 17, 2019, 11 pages. [cited by applicant]
EP09748260.8 , “Written Submission—Strawman Limited”, Mar. 11, 2021, 2 pages. [cited by applicant]
EP17175191.0 , “Decision to Refuse”, Jul. 5, 2019, 14 pages. [cited by applicant]
EP17175191.0 , “Extended European Search Report”, Nov. 8, 2017, 10 pages. [cited by applicant]
EP17175191.0 , “Office Action”, Mar. 2, 2018, 14 pages. [cited by applicant]
EP17175191.0 , “Office Action”, May 25, 2018, 4 pages. [cited by applicant]
EP17175191.0 , “Office Action”, Feb. 12, 2018, 8 pages. [cited by applicant]
EP17175191.0 , “Summons to Attend Oral Proceedings”, Nov. 29, 2018, 6 pages. [cited by applicant]
EP19174517.3 , “Office Action”, Apr. 14, 2021, 4 pages. [cited by applicant]
EP19174517.3 , “Office Action”, Apr. 26, 2022, 5 pages. [cited by applicant]
EP19174517.3 , “Partial European Search Report”, Nov. 25, 2019, 16 pages. [cited by applicant]
EP19174517.3 , “Notice of Opposition”, Sep. 27, 2023, 49 pages. [cited by applicant]
EP2009074826.0 , “Third Party Observation”, Jul. 25, 2017, 3 pages. [cited by applicant]
EP2009074826.0 , “Third Party Observation”, Aug. 14, 2017, 8 pages. [cited by applicant]
Ertl et al., “Impact of AAV Capsid-specific T-Cell Responses on Design and Outcome of Clinical Gene Transfer Trials With Recombinant Adeno-Associated Viral Vectors: An Evolving Controversy”, Human Gene Therapy, vol. 28,… [cited by applicant]
Evans et al., “Molecular Cloning of a cDNA Encoding Canine Factor IX”, Blood, vol. 74, No. 1, Jul. 1989, pp. 202-212. [cited by applicant]
Evens et al., “Haemophilia Gene Therapy: From Trailblazer to Gamechanger”, Haemophilia, vol. 24, 2018, pp. 50-59. [cited by applicant]
Fallaux et al., “Who's Afraid of Replication-competent Adenoviruses?”, Gene Therapy, vol. 6, No. 5, May 1999, pp. 709-712. [cited by applicant]
Finn et al., “Factor IX-R338L (FIX Padua) as a Novel Alternative for the Treatment of Canine Severe Hemophilia B”, Molecular Therapy, vol. 18, Supplement 1, May 2010, p. S239. [cited by applicant]
Finn et al., “FIX-R338L (FIX Padua) as a Successful Alternative for the Treatment of Canine Severe Hemophilia B”, Blood, vol. 114, No. 22, Nov. 2009, pp. 694-694. [cited by applicant]
Finn et al., “The Efficacy and the Risk of Immunogenicity of FIX Padua (R338L) in Hemophilia B Dogs Treated by AAV Muscle Gene Therapy”, Blood, The Journal of the American Society of Hematology, vol. 120, No. 23, Nov. 2… [cited by applicant]
Flotte et al., “Adeno-Associated Viral Vectors for Gene Therapy”, Laboratory Techniques in Biochemistry and Molecular Biology, vol. 31, 2005, 45 pages. [cited by applicant]
Franchini et al., “Treatment of Hemophilia B: Focus on Recombinant Factor IX”, Biologics: Targets and Therapy, vol. 7, No. 1, 2013, pp. 33-38. [cited by applicant]
French et al., “Complete Correction of Hemophilia B Phenotype by Fix-padua Skeletal Muscle Gene Therapy in an Inhibitor-Prone Dog Model”, Blood Advances, vol. 2, No. 5, Mar. 13, 2018, pp. 505-508. [cited by applicant]
French et al., “What is a Conservative Substitution?”, Journal of Molecular Evolution, vol. 19, Mar. 1983, pp. 171-175. [cited by applicant]
Friedler et al., “Development of a Functional Backbone Cyclic Mimetic of the HIV-1 Tat Arginine-Rich Motif”, The Journal of Biological Chemistry, vol. 275, No. 31, Aug. 2000, pp. 23783-23789. [cited by applicant]
Furie et al., “A Practical Guide to the Evaluation and Treatment of Hemophilia”, Blood, vol. 84, No. 1, Jul. 1, 1994, pp. 3-9. [cited by applicant]
Gao et al., “Clades of Adeno-Associated Viruses Are Widely Disseminated in Human Tissues”, Journal of Virology, vol. 78, No. 12, Jun. 2004, pp. 6381-6388. [cited by applicant]
Gao et al., “Novel Adeno-Associated Viruses from Rhesus Monkeys as Vectors for Human Gene Therapy”, Proceedings of the National Academy of Sciences of the United States of America, vol. 99, No. 18, Sep. 3, 2002, pp. 118… [cited by applicant]
George et al., “Hemophilia B Gene Therapy with a High-Specific-Activity Factor IX Variant”, The New England Journal of Medicine, vol. 377, No. 23 (Exhibit 2079), Dec. 7, 2017, pp. 2215-2227. [cited by applicant]
Giannelli et al., “Haemophilia B (Sixth Edition): A Database of Point Mutations and Short Additions and Deletions”, Nucleic Acids Research, vol. 24, No. 1, Jan. 1, 1996, pp. 103-118. [cited by applicant]
Giannelli et al., “Haemophilia B: Database of Point Mutations and Short Additions and Deletions”, Nucleic Acids Research, vol. 18, No. 14, 1990, pp. 4053-4059. [cited by applicant]
Goree et al., “Characterization of the Mutations Causing Hemophilia B in 2 Domestic Cats”, Journal of Veterinary Internal Medicine, vol. 19, No. 2, Mar.-Apr. 2005, pp. 200-204. [cited by applicant]
Gostout et al., “Germline Mutations in The Factor Ix Gene: A Comparison Of The Pattern In Caucasians And Non-Caucasians”, Human Molecular Genetics, vol. 2, No. 3, Mar. 1993, pp. 293-298. [cited by applicant]
Graham et al., “The Malmo Polymorphism of Coagulation Factor IX, An Immunologic Polymorphism Due to Dimorphism of Residue 148 That is in Linkage Disequilibrium with Two Other F.IX Polymorphisms”, American Journal of Hum… [cited by applicant]
Green , “Hemophilia B Mutational Analysis”, Hemostasis and Thrombosis Protocols, vol. 31, 1999, pp. 159-167. [cited by applicant]
Gui et al., “Circulating and Binding Characteristics of Wild-Type Factor IX and Certain Gia Domain Mutants in Vivo”, Blood, vol. 100, No. 1, 2002, pp. 153-158. [cited by applicant]
Hamaguchi et al., “Expression and Characterization of Human Factor IX”, The Journal of Biological Chemistry, vol. 266, No. 23, Aug. 15, 1991, pp. 15213-15220. [cited by applicant]
Hamaguchi et al., “Mutations in the Catalytic Domain of Factor IX That Are Related to the Subclass Hemophilia Bm”, Biochemistry, vol. 32, No. 25, Jun. 29, 1993, pp. 6324-6329. [cited by applicant]
Hasbrouck et al., “AAV-Mediated Gene Transfer for the Treatment of Hemophilia B: Problems and Prospects”, Gene Therapy, vol. 15, No. 11, Jul. 2008, pp. 870-875. [cited by applicant]
Hertzberg et al., “Construction, Expression, and Characterization of a Chimera of Factor IX and Factor X”, The Journal of Biological Chemistry, vol. 267, No. 21, Jul. 25, 1992, pp. 14759-14766. [cited by applicant]
Herzog et al., “Influence of Vector Dose on Factor Ix-specific T and B Cell Responses in Muscle-directed Gene Therapy”, Human Gene Therapy, vol. 13, No. 11, Jul. 20, 2002, pp. 1281-1291. [cited by applicant]
Herzog et al., “Long-Term Correction of Canine Hemophilia B by Gene Transfer of Blood Coagulation Factor IX Mediated by Adeno-Associated Viral Vector”, Nature Medicine, vol. 5, No. 1, Jan. 1999, pp. 56-63. [cited by applicant]
Herzog et al., “Stable Gene Transfer and Expression of Human Blood Coagulation Factor IX After Intramuscular Injection of Recombinant Adeno-associated Virus”, Proceedings of the National Academy of Sciences of the Unite… [cited by applicant]
High , “The Gene Therapy Journey for Hemophilia: Are We There Yet?”, Blood, vol. 120, No. 23, Nov. 29, 2012, pp. 4482-4487. [cited by applicant]
Hopfner et al., “Converting Blood Coagulation Factor 1Xa into Factor Xa: Dramatic Increase in Amidolytic Activity Identifies Important Active Site Determinants”, The European Molecular Biology Organization Journal, vol.… [cited by applicant]
IPR2020-00388 , “Judgement Granting Request for Adverse Judgement after Institution of Trial”, Mar. 25, 2021, 6 pages. [cited by applicant]
IPR2021-00925 , “Affidavit of Duncan Hall re: Internet Archive Records regarding Ex. 1062, Monahan; Ex. 1063, Monahan II; submitted as Exhibit 1086”, May 4, 2021, 280 pages. [cited by applicant]
IPR2021-00925 , “Corrected Declaration of James L. Mullins. Ph.D.”, Before the Patent Trial and Appeal Board, Jan. 6, 2022, 831 pages. [cited by applicant]
IPR2021-00925 , “Decision Granting Institution of Inter Partes Review”, Nov. 17, 2021, 33 pages. [cited by applicant]
IPR2021-00925 , “Decision Granting Patent Owner's Unopposed Motions for Admission Pro Hac Vice of Joshua L. Stern and James M. Lyons 37 C.F.R. § 42.10”, Before the Patent Trial and Appeal Board, Feb. 8, 2022, 4 pages. [cited by applicant]
IPR2021-00925 , “Decision Granting Petitioner's Motions for Pro Hac Vice Admission of Kathryn S. Kayali 37 C.F.R. § 42.10”, Before the Patent Trial and Appeal Board, Jan. 25, 2022, 4 pages. [cited by applicant]
IPR2021-00925 , “Declaration of James L. Mullins, Ph.D., Exhibit 1061”, May 6, 2021, 1659 pages. [cited by applicant]
IPR2021-00925 , “Declaration of Kathryn S. Kayali in Support of Motion for Pro Hac Vice Admission Pursuant to 37 C.F.R. § 42.10(C)”, Before the Patent Trial and Appeal Board, Jan. 10, 2022, 5 pages. [cited by applicant]
IPR2021-00925 , “Declaration of Lee Pedersen, Ph.D., Executed May 6, 2021 Exhibit 1094”, Jun. 5, 2021, 90 pages. [cited by applicant]
IPR2021-00925 , “File History of U.S. Appl. No. 14/981,981, Exhibit 1090”, May 11, 2021, 2672 pages. [cited by applicant]
IPR2021-00925 , “File History of U.S. Appl. No. 15/650,070, Exhibit 1091”, May 11, 2021, 150 pages. [cited by applicant]
IPR2021-00925 , “File History of U.S. Appl. No. 15/989,665, Exhibit 1089”, May 11, 2021, 137 pages. [cited by applicant]
IPR2021-00925 , “File History of U.S. Pat. No. 9,249,405, as Exhibit 1010”, May 11, 2021, 174 pages. [cited by applicant]
IPR2021-00925 , “Order Granting Petitioner's Motions for Pro Hac Vice Admission of Kathryn S. Kayali 37 C.F.R. § 42.10”, Before the Patent Trial and Appeal Board, Jan. 25, 2022, 4 pages. [cited by applicant]
IPR2021-00925 , “Order Granting Petitioner's Unopposed Motion for Supplemental Information 37 C.F.R § 42.123(a)”, Before the Patent Trial and Appeal Board, Jan. 12, 2022, 4 pages. [cited by applicant]
IPR2021-00925 , “Patent Owner's Sur-Reply”, Sep. 21, 2021, 11 pages. [cited by applicant]
IPR2021-00925 , “Petition for Inter Partes Review of U.S. Pat. No. 9,982,248”, May 11, 2021, 81 pages. [cited by applicant]
IPR2021-00925 , “Petitioner Pfizer Inc.'s First Updated Mandatory Notices”, Before the Patent Trial and Appeal Board, Jan. 11, 2022, 5 pages. [cited by applicant]
IPR2021-00925 , “Petitioner's Authorized Reply to Patent Owner's Preliminary Response”, Sep. 14, 2021, 5 pages. [cited by applicant]
IPR2021-00925 , “Pfizer Inc.'s Motion for Pro Hac Vice Admission of Kathryn S. Kayali Pursuant to 37 C.F.R. § 42.10(C)”, Before the Patent Trial and Appeal Board, Jan. 11, 2022, 18 pages. [cited by applicant]
IPR2021-00925 , “PTAB email”, Sep. 8, 2021, pp. 1-2. [cited by applicant]
IPR2021-00925 , “Scheduling Order”, Nov. 17, 2021, 12 pages. [cited by applicant]
IPR2021-00925 , “Statutory Disclaimer under 37 CFR § 1.321(a) for U.S. Pat. No. 9,249,405 filed May 31, 2011, Exhibit 1092”, May 11, 2021, 4 pages. [cited by applicant]
IPR2021-00925 , “UniQure N.V. SEC Form 10-K”, Petition for Inter Partes Review of U.S. Pat. No. 9,982,248, Exhibit 1049, Mar. 1, 2021, 259 pages. [cited by applicant]
IPR2021-00926 , “Decision Granting Institution of Inter Partes Review”, Nov. 17, 2021, 41 pages. [cited by applicant]
IPR2021-00926 , “Declaration of Kathryn S. Kayali in Support of Motion for Pro Hac Vice Admission Pursuant to 37 C.F.R. § 42.10(c)”, Before the Patent Trial and Appeal Board, Jan. 10, 2022, 5 pages. [cited by applicant]
IPR2021-00926 , “Patent Owner's Sur-reply”, Sep. 21, 2021, 11 pages. [cited by applicant]
IPR2021-00926 , “Petition for Inter Partes Review of U.S. Pat. No. 9,982,248”, May 11, 2021, 80 pages. [cited by applicant]
IPR2021-00926 , “Petitioner Pfizer Inc.'s First Updated Mandatory Notices”, Before the Patent Trial and Appeal Board, Jan. 11, 2022, 5 pages. [cited by applicant]