Granted Patent
B2
US 12,514,898 · App. 18/680,542 · Granted Jan 6, 2026
Methods of treating prostate cancer with GnRH antagonist
Inventors:
Tine Kold Olesen (New York, NY); Bo-Eric Persson (St-Prex, CH); Per Cantor (Charlottenlund, DK); Egbert A. van der Meulen (Dalby, SE); Jens-Kristian Slott Jensen (Bagsvaerd, DK)
Assignee:
Ferring B.V.
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Abstract
The invention provides methods and dosing regimens for safely and effectively treating androgen-dependent prostate cancer with a gonadotrophin releasing hormone (GnRH) antagonist without causing a testosterone spike and/or other side effect of GnRH agonist therapy such as a urinary tract infection, or an arthralgia-related or cardiovascular side effect.
Claims (10)
1 . A method of treating advanced stage prostate cancer in a human subject with a decreased likelihood of weight gain during treatment compared to treatment with a gonadotrophin releasing hormone (GnRH) agonist, comprising:
administering an initial dose of 240 mg of degarelix to the subject as two subcutaneous injections of 120 mg each at a concentration of 40 mg/mL on the same day, and
administering a maintenance dose of 80 mg of degarelix at a concentration of 20 mg/mL to the subject as one subcutaneous injection, wherein the maintenance dose is administered approximately every 28 days after the previous dose of degarelix for a duration of treatment,
wherein the treated subject has a decreased likelihood of weight gain during treatment compared to treatment with a gonadotrophin releasing hormone (GnRH) agonist.
2 . The method of claim 1 , wherein the subject has locally advanced prostate cancer.
3 . The method of claim 1 , wherein the subject has metastatic prostate cancer.
4 . The method of claim 1 , wherein the subject is less than 65 years old.
5 . The method of claim 1 , wherein the subject has a body mass index of less than 30 kg/m 2 .
6 . The method of claim 1 , wherein the GnRH agonist is leuprolide.
7 . The method of claim 1 , wherein the treatment with a GnRH agonist is treatment with monthly intramuscular injections of 7.5 mg leuprolide.
Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Jul 29, 2024
From: OLESEN, TINE KOLD; PERSSON, BO-ERIC; CANTOR, PER; VAN DER MEULEN, EGBERT A.; JENSEN, JENS-KRISTIAN SLOTT
To: FERRING B.V.
Reel/Frame 068109/0357 →
Priority Claims (1)
EP 08250703
· Feb 29, 2008
· regional
Continuity (7)
References Cited (345)
US 3773919A
· Boswell et al.
· 1973
[cited by applicant]
US 5506207A
· Rivier et al.
· 1996
[cited by applicant]
US 5516887A
· Deghenghi
· 1996
[cited by applicant]
US 5595760A
· Cherif-Cheikh
· 1997
[cited by applicant]
US 5821230A
· Jiang et al.
· 1998
[cited by applicant]
US 5860957A
· Jacobsen et al.
· 1999
[cited by applicant]
US 5863549A
· Tarantino
· 1999
[cited by applicant]
US 5925730A
· Semple et al.
· 1999
[cited by applicant]
US 6214798B1
· Semple et al.
· 2001
[cited by applicant]
US 6503534B1
· Pellet et al.
· 2003
[cited by applicant]
US 6875843B2
· Jacobson
· 2005
[cited by applicant]
US 8841081B2
· Persson
· 2014
[cited by applicant]
US 9415085B2
· Van Der Meulen et al.
· 2016
[cited by applicant]
US 9579359B2
· Olesen et al.
· 2017
[cited by applicant]
US 9592266B2
· Schwach et al.
· 2017
[cited by applicant]
US 9822146B2
· Rasmusse et al.
· 2017
[cited by applicant]
US 9877999B2
· Persson
· 2018
[cited by applicant]
US 20020001588A1
· Sinha
· 2002
[cited by applicant]
US 20040038903A1
· Luck et al.
· 2004
[cited by applicant]
US 20040138610A1
· Cormier et al.
· 2004
[cited by applicant]
US 20050245455A1
· Luck et al.
· 2005
[cited by applicant]
US 20050276854A1
· Trigg et al.
· 2005
[cited by applicant]
US 20070238647A1
· Bowen et al.
· 2007
[cited by applicant]
US 20090018085A1
· Luck et al.
· 2009
[cited by applicant]
US 20090203623A1
· Olesen et al.
· 2009
[cited by applicant]
US 20100286603A1
· Winderstrom
· 2010
[cited by applicant]
US 20110039787A1
· Petri et al.
· 2011
[cited by applicant]
US 20110053846A1
· Luck et al.
· 2011
[cited by applicant]
US 20120172302A1
· Petri et al.
· 2012
[cited by applicant]
US 20190167755A1
· Persson
· 2019
[cited by applicant]
US 20220218782A1
· Olesen et al.
· 2022
[cited by applicant]
US 20220218783A1
· Persson
· 2022
[cited by applicant]
US 20220323538A1
· Persson
· 2022
[cited by applicant]
US 20250134948A1
· Van Der Meulen et al.
· 2025
[cited by applicant]
CN 1411803A
· 2003
[cited by applicant]
CN 102204889
· 2011
[cited by applicant]
EP 02749B1
· 1983
[cited by applicant]
EP 2749811
· 1983
[cited by applicant]
EP 0556034A1
· 1993
[cited by applicant]
EP 1003774B1
· 2000
[cited by applicant]
EP 1630169A2
· 2006
[cited by applicant]
EP 1967202A1
· 2008
[cited by applicant]
FR 2776520
· 1999
[cited by applicant]
WO WO9734923A1
· 1997
[cited by applicant]
WO WO9846634A1
· 1998
[cited by applicant]
WO WO9926964A1
· 1999
[cited by applicant]
WO WO9948517
· 1999
[cited by applicant]
WO WO03006049A1
· 2003
[cited by applicant]
WO WO2006069779A2
· 2006
[cited by applicant]
WO WO2007130809A2
· 2007
[cited by applicant]
WO WO2008017664A2
· 2008
[cited by applicant]
WO WO2008135989A1
· 2008
[cited by applicant]
WO WO2009090189A1
· 2009
[cited by applicant]
WO WO2009101533A1
· 2009
[cited by applicant]
WO WO2010121835A1
· 2010
[cited by applicant]
WO WO2011004260A2
· 2011
[cited by applicant]
WO WO2011066386A1
· 2011
[cited by applicant]
WO WO2012013331A2
· 2012
[cited by applicant]
WO WO2012055905A1
· 2012
[cited by applicant]
U.S. Appl. No. 18/490,376, filed Oct. 19, 2023, Ferring B.V.
[cited by applicant]
U.S. Appl. No. 18/603,026, filed Mar. 12, 2024, Ferring B.V.
[cited by applicant]
U.S. Appl. No. 18/679,184, filed May 30, 2024, Ferring B.V.
[cited by applicant]
“Alkaline Phosphatase,” GP Notebook (Sep. 12, 2011), hitp://gpnotebook.co.uk/simplepage.cfrn?ID==—1932525548.
[cited by applicant]
‘Bone Specific Alkaline Phosphatase,’ The University of Iowa (UIHC), Department of Pathology, Laboratory Services Handbook (Sep. 11, 2011), http://www.healthcare.uiowa.edu/pathhandbook/handbook/iest2238.html.
[cited by applicant]
A. Plantade et al., Locally advanced prostate cancer: definition prognosis and treatment, Bull. Cancer, 94 (7 Suppl.):F50-61, Jul. 2007 (Abstract).
[cited by applicant]
Agerso, et al., “The dosing solution influence on the pharrnacokinetic of degarelix, a new GnRH antagonist, after s.c. administration to beagle dogs,” European Journal orPharmaceutical Sciences, vol. 20, pp. 335-340, 20…
[cited by applicant]
Albertsen et al., Reduced Risk of Cardiovascular (CV) Events and Death in Patients (PTS) Receiving Degarelix Compared with LHRH Agonists (2012).
[cited by applicant]
Albertsen, et aL “Cardiovascular Morbidity Associated with GonadotropinReleasing Hormone Agonist and an Antagonist,” European Urology (2013), https://dx.doi.org/10,16/j.eururo.2013.10,032.
[cited by applicant]
Aldrich, Handbook of Fine Chemicals and Laboratory Equipment—2003-2004 US, Dimethylfo, 734.
[cited by applicant]
Amblard et al., “Methods and Protocols of Modern Solid Phase Peptide Synthesis,” Mol. Biotechnol. 33: 239-254 (2006).
[cited by applicant]
Andersson et al., “Large-Scale Syntllesis of Peptides,” Biopolymers (Peptide Science), pp. 227-250, 2000.
[cited by applicant]
Excerpt from “Austria Codex Fach information 2005/2006 (MINRIN)”.
[cited by applicant]
Bak et al., “Physicochemical and Formulation Developability Assessment forTherapeutic Peptide Delivery—A Primer,” the AAPS Journal, vol. 17, No. 1, pp. 144-155, Jan. 2015.
[cited by applicant]
Behn, et al., “The obesity epidemic and its cardiovascular consequences,” (2006) Curr. Opin. Cardiol. vol. 21, pp. 353-360.
[cited by applicant]
Berges, et al., “Effect of a new leuprorelin formulation on testosterone levels in patients with advanced prostate cancer,” (2006), Cur. Med. Res. Opin., vol. 22, No. 4, pp. 649-655.
[cited by applicant]
Blagoeva et al., “Intramolecular Nucleophilic Attack on Carboxylate by Ureide Anion. General Acid-Base Catalysis of The Alkaline Cyclisation of 2,3,3,5-Tetramethylhydantoic Acid” Journal Chemical Society Perkin Transact…
[cited by applicant]
Boccon-Gibod et al., “Degarelix Compared to Leuprolide Depot 7.5 mg in a 12-Month Randomised, Open-Label, Parallel-Group Phase III Study in Prostate Cancer Patients,” Eur. Urol. Suppl. 7:205 (2008).
[cited by applicant]
Boccon-Gibod et al: “Optimising Hormone Therapy in Advanced Disease” European Urology Supllements, vol. 4, No. 8, Nov. 1, 2005 (Nov. 1, 2005), pp. 21-29, XP005112815 ISSN: 1569-9056.
[cited by applicant]
Boccon-Gibod, “Global Update on defining and treating high-risk localized prostate cancer with leuprorelin: a European perspective” JU International, Suppl 1 :2-5, 2007.
[cited by applicant]
Boccon-Gibod, et al., “Cyproterone Acetate Lead-In Prevents Initial Rise of Serum Testosterone Induced by Luteinizing Hormone-Releasing Hormone Analogs in the Treatment of Mestastatic Carcinoma of tl1e Prostate,” (1986)…
[cited by applicant]
Boyle et al: “Treatment of hormone sensitive prostate cancer” Europeanjournal of Cancer. Supplement, Pergamon, Oxford, GB, vol. 3, No. 3, Oct. 1, 2005 (Oct. 1, 2005), pp. 331-338, XP005130027 ISSN: 1359-6349.
[cited by applicant]
Bracarda et al., “Cancer of the Prostate,” Grit. Rev. Oncology i Hematology 56: 379-396 (2005).
[cited by applicant]
Bray, “Large-Scale manufacture of peptide therapeutics by chemical synthesis,” Nature Review, vol. 2, pp. 587-593, Jul. 2003.
[cited by applicant]
Broqua et al., “Effects of the New GNRH Antagonist FE200486 one the Growth of the Adrogen-Dependent Prostate Tumor Dunning R-3327H, 6th International Symposium on GnRH Analogues in Cancer and Human Reproduction,” Geneva…
[cited by applicant]
Broqua, et al., “Pllarmacological Profile of a New, Potent, and Long-Acting Gonadotropin-Releasing Hormone Antagonist: Degarelix,” The Journal ofPharmacology and Experimental Tllerapeutics, vol. 301, pp. 95-102, 2002.
[cited by applicant]
Bubley, “Is the Flare Phenomenon Clinically Significant?” Urology 58:5-9 (2001).
[cited by applicant]
C. Doehn et al., Drug evaluation: Degarelix—a potential new therapy for prostate cancer, IDrugs, 9(8):565-572, 2006.
[cited by applicant]
Cancer Trends Progress Report, 200.1: 2003 Update; 2005 Update; 2007 Update; 2009/2010 Update, http://progressreport.cancer.gov. (last visited Jun. 1, 2012).
[cited by applicant]
Castells et al., “Synthesis of a Chemically Bound Chiral Silica Phase,” Reactive Polymers 6:207-211 (1987).
[cited by applicant]
Cetrotide™ package insert (Aug. 11, 2000).
[cited by applicant]
Chernecky, and Berger, “Laboratory Tests and Diagnostic Procedures,” (2008) Fifth Edition, WB Saunders & Company, Philadelphia. ISBN-978-1-14160-3704-0.
[cited by applicant]
ClinicalTrials.gov, View of NCT00728533 titled “Open-Label, Randomised Parallel-Group Study,” Feb. 19, 2009.
[cited by applicant]
Conn, P. M. “Gonadotropin-releasing hormone and its analogs,” Ann. Rev. Med. (1994) 45:391-405.
[cited by applicant]
Council of Europe, Strasbourg, “European Pharmacopoeia 6263” European Directorate for tile Quality of Meicines & Healthcare (2007).
[cited by applicant]
Council of Europe, Strasbourg, “European PI1armacopoeia6748” European Directorate for tile Quality of Meicines & Healthcare (2007).
[cited by applicant]
Crawford et al., “A Phase III Extension Trial With a 1-Arm Crossover From Leuprolide to Degarelix: Comparison of Gonadotropin-Releasing Hormone Agonist and Antagonist Effect of Prostate Cancer,” 186 The Journal of Urolo…
[cited by applicant]
Crawford et al., “Long term tolerability and efficacy of degarelix: 5-year results from a phase III extension trial with a one-arm crossover from leuprolide to degarelix”, Urologic Oncology, School of Medicine, Universi…
[cited by applicant]
Crawford et al., Degarelix Versus LHRH Agonists: Differential Skeletall Morbidity Outcomes from a Pooled Analysis of Six Comparative Randomised Clinical Trials (2012).
[cited by applicant]
Damber et al., “Comparin 1 Testosterone and PSA for Different Baseline Testosterone Concentrations During Initiation of Degarelix and leuprolide Treatment,” European Urolo w Supplements (2009) 8(4), 130, Abstr No. 39.
[cited by applicant]
De la Rosette et al., “Efficacy and safety of androgen deprivation therapy afterswitching from monthly leuprolide to monthly degarelix in patients with prostate cancer,” 65(5) International Journal of Clinical Practice …
[cited by applicant]
De Pinieux, et al., “Clinical and Experimental Progression of a New Model of Human Prostate Cancer and Therapeutic Approach,” American Journal of Pathology, vol. 159, No. 2,Aug. 2001,753-764.
[cited by applicant]
Debruyne Franse M J: “Gonadotropin-releasing hormone antagonist in the management of prostate cancer.” Reviews in Urology 2004, vol. 6 Suppl 7, 2004, pp. 825-832, XP002527257 ISSN: 1523-6161.
[cited by applicant]
Debruyne, et al., “Abarelix for injectable suspension: first-in-class gonadotropin-releasing hormone antagonist for prostate cancer,” (2006) Future Oncol., vol. 2, pp. 677-696.
[cited by applicant]
Degarelix Study Group Tammela et al: “904Degarelix—a phase 11multicenter, randomized dose-escalating study testing a novel gnrh receptor blocker in prostate cancer patients” Euorpean Urology Supplements, vol. 4, No. 3, …
[cited by applicant]
Demers et al., “Biochemical Markers and Skeletal Metastases,” Cancer, vol. 88, pgsa 2919-2926, Mar. 2, 2000.
[cited by applicant]
Denis, et al., “Overview of Phase III Trials on Combined Androgen Treatment in Patients with Metastatic Prostate Cancer,” (1993) Cancer, vol. 72, pp. 3888-3895.
[cited by applicant]
Doehn Christian et al: “Drug evaluation: Degarelix—a potential new therapy for prostate cancer.” !Drugs: the Investigational Drugs Jounral Aug. 2006, vol. 9, No. 8, Aug. 2006 (Aug. 2006), pp. 565-572, XP009'!05353 ISSN:…
[cited by applicant]
Eastman et al., “Serum Alkaline Phosphatase: Normal Values by Sex and Age,” 23(9) Clinical Chemistry 1769-1770 (1977).
[cited by applicant]
EMEA, European Medicines Agency, “Assessment Report for Firmagon”, Doc. Ref., EMEA/CHMP/635761i2008, pp. 1-67.
[cited by applicant]
Etzioni, et al., “Cancer Surveillance Series: Interpreting Trends in Prostate Cancer—Part III: Quantifying the Link Between Population Prostate-Specific Antigen Testing and Recent Declines in Prostate Cancer Mortality,”…
[cited by applicant]
European Patent Office Communication pursuant to Article 94(3) EPC dated Apr. 10, 2014, in corresponding Application No. 11 776 745.9 (5 pages).
[cited by applicant]
European Search Report & Opinion, dated Oct. 2, 2012, EP Application No. 12168495.5.
[cited by applicant]
Extended European Search Report received in European Patent Application No. 23174353.5 dated Oct. 26, 2023.
[cited by applicant]
FDA Drug Information page—Plenaxis (abarelix for injectable suspension); http://www.fda.gov/cder/drug/infopage/planaxis/default.htm. (Feb. 2004).
[cited by applicant]
FDA Guidance for Industry Q3B(R2) Impurities in New Drug Products, Rev 2 (Jul. 2006).
[cited by applicant]
fda.gov, Label for Degarelix for injection (Dec. 24, 2008), available at www.accessdata.fda.gov/drugsatfda_docs/label/2008/022201 Ibl.pdf, last visited Jun. 4, 2013.
[cited by applicant]
Ferlay, et al., “Estimates of the cancer incidence and mortality in Europe in 2006,” Annals of Oncology, vol. 18, pp. 581-592 (2007).
[cited by applicant]
Ferring BV, “GnRH Antagonists”, Indian Granted Patent IN224650 based on PCT Application W09846634, dated Oct. 22, 1998, pp. 1-43.
[cited by applicant]
[cited by applicant]
Final Office Action received in U.S. Appl. No. 15/845,391 dated Sep. 13, 2023.
[cited by applicant]
Final Office Action received in U.S. Appl. No. 17/710,905 dated Aug. 29, 2022.
[cited by applicant]
Firmagon Package Insert (Dec. 2008).
[cited by applicant]
First Amended Complaint,
[cited by applicant]
Fleming,et al., “Post-therapy changes in PSA as an outcome measure in prostate cancer clinical Trials,” (2006) Nature Clinical Practice Oncolology, vol. 3, No. 12, pp. 658-667.
[cited by applicant]
Forbes, et al., “FDA'S Adverse Drug Reaction Drug Dictionary and Its Role in Post-Marketing Surveillance,” (1986) Drug Inf. J., vol. 20, pp. 135-145.
[cited by applicant]
Frampton et al., “Degarelix”, ADIS International, Drugs, 69 (14): 1967-1976 (2009).
[cited by applicant]
Fresenius Kabi's Initial Invalidity Contentions,
[cited by applicant]
Garnero et al., “Markers of Bone Tumover for the Management of Patients with Bone Metastases from Prostate Cancer,” Br. J. Cancer 82(4): 858-864 (2000).
[cited by applicant]
Garnero, “Markers of bone turnover in prostate cancer,” Cancer Treat. Rev., 27:187-192 (2001).
[cited by applicant]
Garnick M et al: “217 Increase in the electrocardiogramarval in men with prostate cancer undergoing androgen deprivation therapy: Results of three randomized controlled clinical studies”, European Urology Supplements, v…
[cited by applicant]
Gerlinger, et al., “Recommendation for Confidence interval and sample size calculations for the Pearl Index,” (2003) The European Journal of Contraception and Reproductive Health Care, vol. 8, pp. 87-92.
[cited by applicant]
Gillum, T., “The Merck Regulatory Dictionary: A Pragmatically Develop Drug Effects Vocabulary,” (1989) Drug Info. J., vol. 23, pp. 217-220.
[cited by applicant]
Gittelman et al., “A 1-Year, Open Label, Randomized Phase II Dose Finding Study of Degarelix for the Treatment of Prostate Cancer in North America,” J Urol, vol. 180, pp. 1986-1992 (Nov. 2008).
[cited by applicant]
Gittelman et al., “Degarelix: A gonadotropin-releasing hormone receptor (GnRH) blocker, tested in two one-year multicenter, randomized, dose-finding studies in prostate cancer patents,” J. Clin. Oncol. 24:14516 (2006).
[cited by applicant]
Gittelman et al: “MP-08.21: A multicentre, randomised one year dose-finding study of degarelix, a gonadotrophin-releasing hormone (GnRH) receptor blocker in prostate caner patients” Urology, Belle Mead, NJ, US vol. 70 N…
[cited by applicant]
Gonzalez-Barcena D et al: “Luteinzing hormone-releasing hormone hormone antagonist centrorelix as primary single therapy in patients with advanced prostatic cancer and paraplegia due to metastatic invasion of spinal cor…
[cited by applicant]
Gotsman et al., “Tcell costimulation and coinhibition in atherosclerosis,” Circulation Res 103:1220-1231 (2008).
[cited by applicant]
Granfors, et al., “Combined Orchiectomy and External Radiotherapy VersusRadiotherapy Alone for Nonmetastatic Prostate Cancer With or Without Pelvic Lymph Node Involvement: A Prospective Randomized Study,” J. UroL, (1998…
[cited by applicant]
Greiman et al., “Approach to Androgen Deprivation in the Prostate Cancer Patient with Pre-existing Cardiovascular Disease,” Cur Urol Rep 18:41 (2017).
[cited by applicant]
Hachmann et al., “Alternative to Piperidine in Fmoc Solid-Phase Synthesis,” J. Comb. Chem. 8:149 (2006).
[cited by applicant]
Hackman, et aL, “Emerging Risk Factors for Atl1eroslemtic Vascular Disease,” (2003), JAMA, vol. 290, pp. 932-940.
[cited by applicant]
Hegele et al., “Biochemical Markers of Bone Turnover in Patients with Localized andMetastasized Prostate Cancer,” Journal Compilation, vol. 99, pp. 330-334, Sep. 7, 2006.
[cited by applicant]
Heidenreich et al., “Welche Mechanisrnen Liegen Der Besseren Kontrolle Des Psa-Progressionsfreien Uberlebens Von Degarelix Im Vergleich Mit Leuprorelin Zugrunde?”, RWfH, Aache, Ferring Arzneimittel GmbH, Kiel, 4 pages.
[cited by applicant]
Hellerstedt, et al., “The Current State of Horrnonal Therapy for Prostate Cancer,” CA a Cancer Journal for Clinicians, vol. 52, pp. 154-179. (2002).
[cited by applicant]
Holdaway, et al. “Treatment of metastatic prostate carcinoma with the depot LRH analog Zoladex,” The Prostate 12: 199-127 (1988).
[cited by applicant]
Huggins et al., “I. The Effect of Castration, of Estro 1en and of Androgen Injection on Serum Phosphatases in Metastatic Carcinoma of ttie Prostate,” J. of Urol. (2002) 168:9-12.
[cited by applicant]
Huggins et al., “Studies on Prostatic Cancer I. The Effect of Castration, of Estrogenand of Androgen Injection on Serum Ptiosphatases in Metastatic Carcinoma of the Prostate,” Cancer Res. 1:293-297 (1941).
[cited by applicant]
Huggins et al., “Studies on Prostatic Cancer. I. The Effect of Castration, of Estrogenand of Androgen Injection on Serum Phosphatases in Metastatic Carcinoma of the Prostate,” Cancer Res. (194.1) 1 :293-297.
[cited by applicant]
Huirne J A et al: “Gonadotropin-releasing-hormone-receptor antagonists” Lancet The, Lancet Limited. London, GB, vol. 358, No. 9295, Nov. 24, 2001 (Nov. 24, 201), pp. '1793-1803, XP04805574 ISSN: 0140-6736.
[cited by applicant]
International Search Report issued on Sep. 12, 2002, in Application No. PCT/GB02/03⋅i 16.
[cited by applicant]
Isidro-Llobet et al., “Amino Acid-Protecting Groups,” Chern. Rev, pp. 2455-2504, 2009.
[cited by applicant]
Iversen et al., “Improved outcomes with degarelix monotherapy compared with luteinizing hormone-releasing hormone (LHRH) agonists plus antiandrogen in the treatment of men with advanced prostate cancer”, 29th Congress o…
[cited by applicant]
Iversen et al: “MP-08.18” Urology, Belle fVIEAD, NJ, US, vol. 68, Nov. 1, 2006 (Nov. 1, 2006), p. 102, XP05709326 ISSN 0090-4295.
[cited by applicant]
Iverson et al., “Determining the optimal initiation and maintenance dose of degarelix for hormone therapy of prostate cancer patients,” Urology 68 (Supplement 5A) (2006).
[cited by applicant]
Jadhav et al., “Semi-Mechanistic Pharmacodynamic Modeling for Degarelix, a Novel Gonadotrophin Releasing Hormone (GnRH) Blocker,” J. of Pharmacokinetics and Pharmacodynamics, vol. 13, No. 5, Oct. 2006.
[cited by applicant]
Jensen, Peptide Synthesis and Applications, 1047 Methods in Molecular Biology (Jensen et al., eds.) (2013) (252 pgs).
[cited by applicant]
Jiang et al., “Betidamino Acid-Scan of the GNRH Antagonist Acyline,” Journal of Medicinal Chemistry, American Chemical Socitey, Washington, US, vol. 40, 1997, pp. 3739-3748.
[cited by applicant]
Jiang, et al., “GnRH Antagonists: A New Generation of Long Acting Analogues Incorporating p-Ureido-phenylalanies at Positions 5 and 6,” (2001) J. Med. Chem, vol. 44, pp. 453-467.
[cited by applicant]
Kaneti et al., “Thorpe-Ingold effects in cyclizations to five-membered and six-membered rings containing planar segments. The rearrangement of N(1)-alkylsubstituted dihydroorotic acids to hydantoinacetic acids in base,”…
[cited by applicant]
Keating Nancy L et al: “Diabetes and cardiovascular disease during androgen deprivation therapy for prostate cancer.” Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology Sep. 20, …
[cited by applicant]
Kevin K.-C. Liu, Subas l'vt Sakya, Christopher J. O'donnell, Andrew C.Flick, and Jin Li, “Synthetic Approaches to the 2009 New Drugs”, Biorganic and Medicinal Chemistry 19, (2011), pp. 1136-1154.
[cited by applicant]
Kirk et al., “Immediate Versus deferred treatment for advanced prostatic cancer; initial results of the Medical Researcll Counsel trial.,” Britisll Journal of Urology, (1997) vol. 79, pp. 235-246.
[cited by applicant]
Klotz et al., “Disease Control Outcomes from Analysis of Pooled Individual Patient Data from Five Comparative Randomised Clinical Trials of Degarelix Versus Luteinizing Hormone-releasing Hormone Agonists,” European Urol…
[cited by applicant]
Klotz, et al., “The efficacy and safety of degarelix: a ⋅ 12-month, comparative, randomized, open-label, parallel-group phase III study in patients with prostate cancer,” BJU International, 102, pp. 1531-1538, Nov. 2.1,…
[cited by applicant]
Koedjikov et al., “B-Ureido Acid and Dihydrouracils. Part 15. Effect of Allylic Strain on Ring Opening of 1,6-Disubstituted Dihydrouracils” Journal Chemical Society Perkin Transactions II 1077-1081 (1984).
[cited by applicant]
Lee et al, “Prostate-Specific Antigen Doubling Time Predicts Clinical Outcome and Survival in Prostate Cancer Patients Treated with Combined Radiation and Hormone Therapy” Int J Radiation Oncology 63:456-462, 2005.
[cited by applicant]
Lehmann, “Testing Statistical Hypotheses,” (1986) Second Edition, John Wiley & Sons, New York, ISBN 0-471-84083-1.
[cited by applicant]
Levine, et al., “Androgen-Deprivation Therapy in Prostate Cancer and Cardiovascular Risk,” Circulation, 2010; 121; pp. 833-840.
[cited by applicant]
Lilja, et al., “Prostate-specific antigen and prostate cancer: prediction, detection and monitoring,” (2008) Nature Reviews/Cancer, vol. 8, pp. 268-278.
[cited by applicant]
Lukka, et al., “Maximal androgen blockade for the treatment of metastatic prostate cancer—a systematic review,” Current Oncology, vol. 13, No. 3, pp. 81-93. (2006).
[cited by applicant]
Lupron Depot Prescribing Information (2019).
[cited by applicant]
Lyseng-Williamson, Katherine A., “Degarelix: a guide to its use in advanced prostate cancer,” 28(5) Drugs Ther. Perspect. 6-10 (2012).
[cited by applicant]
M. Bolla et al., Improved Survival in Patients with Locally Advanced Prostate Cancer Treated with Radiotherapy and Goserelin, N. Eng. J. Med., 337(5)295-300 (1997).
[cited by applicant]
Magnusson P. et al, “Differences of bone alkaline phosphatase isoforms in metastatic bone disease and discrepant effects of clodronate on different skeletal sites indicated by the location of pain,” Clinical Chemistry (…
[cited by applicant]
Malkin, “Are techniques used for intramuscular injection based on research evidence?” nursingtimes.net, Nursing Times: 104; 50/51, 48-51 Dec. 16, 2008.
[cited by applicant]
Manning et al., “Stability of Protein Pharmaceuticals: An Update,” Pharmaceutical Research, vol. 27, No. 4, pp. 544-575, Apr. 2010.
[cited by applicant]
Mason et al., “Neoadjuvant Androgen Deprivation Therapy for Prostate Volume Reduction, Lower Urinary Tract Symptom Relief and Quality of Life Improvement in Men with Intermediate-to High-risk Prostate Cancer: A Randomis…
[cited by applicant]
Mason et al., “Neoadjuvant androgen deprivation therapy for prostate vol. reduction,” Clinical Oncology 25 (2013) 190-196.
[cited by applicant]
Mcneil, et al., “On the Elicitation of Preferences for Alternative Therapies,” (1982) N. Engl. J. Med., vol. 306, No. 21, pp. 1259-1262.
[cited by applicant]
MedDRA website, http://www.meddramsso.com. (2009).
[cited by applicant]
Messing, et al., “Immediate Hormonal Therapy Compared with Observation after Radical Prostatectomy and Pelvic Lyphadenectorny in Men with Node-Positive Prostate Cancer,” (1999), N. Eng. Jc Mede, vol. 341, pp. 1781-1788.
[cited by applicant]
Miller et al., Differential outcomes from an analysis of six comparative randomised clinical trials of degarelix versus luteinising hormone-releasing hormone (LHRH) agonists) (2012).
[cited by applicant]
Miller et al., “Disease control-related outcomes from an analysis of six comparative randomised clinical trials of degarelix versus luteinising llormone-releasing hormone(LHRH) agonists,” (2012).
[cited by applicant]
Mongiat-Artus Pet al: “Role of Luteinising Hormone Releasing Hormone (LHRH) Agonists and Hormonal Treatment in the Management of Prostate Cancer” European Urology Supplements, vol. 4, No. 5, Jul. 1, 205 (Jul. 1, 2005), …
[cited by applicant]
Mongiat-Artus, et al., “Abarelix: the first gonadotrophin-releasing hormone antagonist for the treatment of prostate cancer,” (2004), Expert Opin. Pharmacother, vol. 5, pp. 2171-2172'179.
[cited by applicant]
Montalbetti et aL, “Amide bond formation and peptide coupling,” Science Direct (Tetrahedron 2005), pp. '10827-10852.
[cited by applicant]
Nalesnik J.G. et al, “Anemia in men with advanced prostate cancer: Incidence, etiology, and treatment,” Reviews in Urology (2004) 6(1): 1-4.
[cited by applicant]
National Cholesterol Education Program (NCEP) Guidelines for Interpretation of Lipid Values, (2001; updated 2004) XP-02729834.
[cited by applicant]
NCEP ATP III Classification of Total Cholesterol, LDL-C, and HDL-C, XP-02729835 (2003 first publication; 2010).
[cited by applicant]
Non-Final Office Action issued on Jun. 3, 2022, in U.S. Appl. No. 17/710,905.
[cited by applicant]
Non-Final Office Action received in U.S. Appl. No. 15/845,391 dated Jan. 26, 2023.
[cited by applicant]
Non-Final Office Action received in U.S. Appl. No. 16/880,608 dated Oct. 27, 2022.
[cited by applicant]
Non-Final Office Action received in U.S. Appl. No. 17/199,733 dated Mar. 5, 2024.
[cited by applicant]
Non-Final Office Action received in U.S. Appl. No. 17/710,889 dated Jul. 11, 2022.
[cited by applicant]
Non-Final Office Action received in U.S. Appl. No. 17/710,889 dated Oct. 4, 2022.
[cited by applicant]
Non-Final Office Action received in U.S. Appl. No. 17/710,899 dated Aug. 18, 2022.
[cited by applicant]
Non-Final Office Action received in U.S. Appl. No. 17/710,899 dated Dec. 30, 2022.
[cited by applicant]
Non-Final Office Action received in U.S. Appl. No. 17/829,134 dated Nov. 4, 2022.
[cited by applicant]
Notice of Allowance received in U.S. Appl. No. 16/880,608 dated May 12, 2023.
[cited by applicant]
Notice of Allowance received in U.S. Appl. No. 17/710,899 dated Jul. 19, 2023.
[cited by applicant]
Notice of Opposition against EP2249859 to Ferring B.V., filed Jan. 23, 2015.
[cited by applicant]
Notice of Opposition against EP2505204 to Ferring B.V., filed Sep. 24, 2015.
[cited by applicant]
Notice of Opposition against EP2650012 to Ferring B.V., filed Dec. 24, 2015.
[cited by applicant]
Notice of Third Party Opposition, filed on Jan. 23, 2015, in EP 2249859.
[cited by applicant]
Office Action, dated Apr. 19, 2019) U.S. Appl. No. 15/405,552.
[cited by applicant]
Office Action dated Feb. 8, 2017, U.S. Appl. No. 14/747,218.
[cited by applicant]
Office Action dated Jan. 2, 2019, U.S. Appl. No. 15/205,108.
[cited by applicant]
Office Action dated Jan. 29, 2016, U.S. Appl. No. 12/155,897.
[cited by applicant]
Office Action dated Jan. 29, 2016, U.S. Appl. No. 12/901,270.
[cited by applicant]
Office Action dated Jan. 9, 2014, U.S. Appl. No. 12/829,467.
[cited by applicant]
Office Action dated Jul. 14, 2016, U.S. Appl. No. 14/454,825.
[cited by applicant]
Office Action dated Mar. 10, 2016, U.S. Appl. No. 14/139,922.
[cited by applicant]
Office Action dated Mar. 24, 2016, U.S. Appl. No. 13/458,330.
[cited by applicant]
Office Action dated Mar. 5, 2014, U.S. Appl. No. 12/155,897.
[cited by applicant]
Office Action dated Mar. 6, 2014, U.S. Appl. No. 12/901,270.
[cited by applicant]
Office Action dated Oct. 8, 2013, U.S. Appl. No. 13/381,762.
[cited by applicant]
Office Action dated Sep. 12, 2017, U.S. Appl. No. 12/901,270.
[cited by applicant]
Office Action mailed Apr. 8, 2016, U.S. Appl. No. 14/403,775.
[cited by applicant]
Office Action mailed May 20, 2014, in co-pending U.S. Appl. No. 13/458,330.
[cited by applicant]
Office Action dated Apr. 7, 2017, U.S. Appl. No. 12/368,935.
[cited by applicant]
Office Action dated Aug. 12, 2019, in U.S. Appl. No. 15/205,108.
[cited by applicant]
Office Action (non-final) dated Feb. 19, 2016, U.S. Appl. No. 14/454,825.
[cited by applicant]
Office Action (non-final) dated Jun. 16, 2016, U.S. Appl. No. 14/747,218.
[cited by applicant]
Office Action (non-final) dated Jun. 30, 2015, U.S. Appl. No. 13/458,330.
[cited by applicant]
Office Action (non-final) dated Jun. 5, 2015, U.S. Appl. No. 12/155,897.
[cited by applicant]
Office Action (non-final) mailed Jun. 4, 20.15, U.S. Appl. No. 14/139,922.
[cited by applicant]
Office Action (non-final) mailed Jun. 5, 20.15, U.S. Appl. No. 12/901,270.
[cited by applicant]
Office Action (non-final) mailed Sep. 3, 2015, U.S. Appl. No. 14/403,775.
[cited by applicant]
Office Action dated Apr. 10, 2018, U.S. Appl. No. 12/901,270.
[cited by applicant]
Office Action dated Dec. 19, 2017, U.S. Appl. No. 15/420,156.
[cited by applicant]
Office Action dated Jul. 25, 2013, U.S. Appl. No. 12/829,467.
[cited by applicant]
Office Action dated Jul. 26, 2013, U.S. Appl. No. 12/901,270.
[cited by applicant]
Office Action dated Jun. 11, 2013, U.S. Appl. No. 13/381,762.
[cited by applicant]
Office Action dated Jun. 28, 2018, U.S. Appl. No. 15/405,552.
[cited by applicant]
Office Action dated Jun. 6, 2013, U.S. Appl. No. 12/774,113.
[cited by applicant]
Office Action dated Mar. 26, 2018, U.S. Appl. No. 15/205,108.
[cited by applicant]
Office Action dated May 5, 2015, U.S. Appl. No. 13/881,751.
[cited by applicant]
Office Action dated Nov. 1, 2018, in U.S. Appl. No. 12/901,270.
[cited by applicant]
Office Action dated Sep. 11, 2013, in U.S. Appl. No. 12/771,199.
[cited by applicant]
Office Action dated Sep. 3, 2013, in U.S. Appl. No. 13/458,330.
[cited by applicant]
Office Action mailed Apr. 2, 2012, in U.S. Appl. No. 12/368,935.
[cited by applicant]
Office Action mailed Aug. 27, 2014 in U.S. Appl. No. 13/881,744.
[cited by applicant]
Office Action mailed Dec. 3, 2013, in U.S. Appl. No. 12/368,713.
[cited by applicant]
Office Action mailed Feb. 4, 2020, in U.S. Appl. No. 16/224,843.
[cited by applicant]
Office Action mailed Jan. 31, 2013, in U.S. Appl. No. 12/901,270.
[cited by applicant]
Office Action mailed Jul. 8, 2016, U.S. Appl. No. 15/205,108.
[cited by applicant]
Office Action mailed Mar. 1, 2011, in U.S. Appl. No. 12/368,713.
[cited by applicant]
Office Action mailed Mar. 30, 2017, in U.S. Appl. No. 14/454,825.
[cited by applicant]
Office Action mailed Mar. 8, 20.11, in U.S. Appl. No. 12/155,897.
[cited by applicant]
Office Action mailed Oct. 12, 2011, in U.S. Appl. No. 12/155,897.
[cited by applicant]
Office Action mailed Oct. 2, 2014, in U.S. Appl. No. 12/829,467.
[cited by applicant]
Office Action mailed Oct. 22, 2009, in U.S. Appl. No. 12/155,897.
[cited by applicant]
Office Action received in Japanese Patent Application No. 2022-142833, dated Sep. 26, 2023.
[cited by applicant]
Ozono, et al., “Efficacy and safety of a 3-month dosing regimen of degarelix in Japanese patients with prostate cancer: a phase II maintenance-dose-finding study, ”Jpn J Clin Oncol. (2017) 47(5): 438-446.
[cited by applicant]
Paragraph IV Letter, filed by Fresenius Kabi against Ferring Pharmaceutical, Feb. 10, 2020 (redacted).
[cited by applicant]
People's Republic of China First Office Action dated Feb. 25, 2013 in Application No. 201080019696.2, 2 pages.
[cited by applicant]
Persad, “Leuprorelin Acetate in Prostate Cancer: A European Update,” (2002) Int. J. Clin. Pract., vol. 56, No. 5, pp. 389-396.
[cited by applicant]
Price, Highlights from the 29th European Society for Medical Oncology Congress, Vienna, Austria Oct. 29 through Nov. 2, 2004—Update on the 36-Menth Data from the Phase 111 Trial D9901 of Proveoge® Immunotherapy hi Prost…
[cited by applicant]
Princivalle et al. “Rapid Suppression of Plasma Testosterone Levels and TumorGrowth in the Dunning Rat Model Treated with Degarelix, a New Gonadotrophin-Releasing Hormone Antagonist,” J. Pharrnacol. Exp. Ther. 320(3):11…
[cited by applicant]
Proteins and Proteomics: A Laboratory Manual 1st Edition by Richard J. Simpson Publisher: Cold Spring Harbor Laboratory Pr; 1st edition (Dec. 1, 2002)—“Reversed-phase High-performance Liquid Chromatography” (284 pages).
[cited by applicant]
Rahimy et al, “Suppression of Plasma Testosterone and Prostate Carcinoma Size by a Redox-Based, Brain-Targeted Estrogen Delivery System in the Rat” Prostate 23:79-90, 1993.
[cited by applicant]
Ramaswamy et al., “Serum Levels of Bone Alkaline Posphatase in Breast and Prostate Cancers with Bone Metastasis,” Indian Journal of Clinical Biochemistry, p 1s. 110-113, 15(2), 2000.
[cited by applicant]
Rivier, J. et al., “Gonadotropin-releasing hormone antagonists with N′- Triazolylomithine, -lysine, or -p-aminophenylalanine residues at positions 5 and 6.” Journal of Medical Chemistry (1992) 35:4270-4278.
[cited by applicant]
Romero-Corral, et al., “Association of bodyweight with total mortality and withcardiovascular events in coronary artery disease: a systematic review of cohort studies,” (2006) Lancet, 368:666-678.
[cited by applicant]
Ruczynski et al., “Problem of Aspartimide Formation in Fmoc-Based Solid-Phase Peptide Synthesis Using Dmab Group to Protect Side Chain of Aspartic Acid” J. Peptide Sci. 14:335-341 (2008).
[cited by applicant]
Saltzman, A, “Adverse Reaction Terminology Standardization: A Report on Schering-Plough's Use of the WHO Dictionary and the Formation of the WHO Adverse Reaction Terminology Users Group (WUG) Consortium,” (1985) Drug In…
[cited by applicant]
Samant et al., “Novel analogues of degarelix incorporating hydroxy-, methoxy- and pegylated-urea moieties at postions 3, 5, 6 and the N-terminus,” J. Med Chem. 49('12), pp. 3536-3543,2006.
[cited by applicant]
Sartor, 0. “Eligard® 6: A new form of treatment for prostate cancer,” European Urol. Supp. (2006) 5: 905-910.
[cited by applicant]
Schwach et al., “Biodegradable PLGA microparticles for sustained release of a new GnRH antagonist . . . ,” European Journal of Pharmaceutics and Biopharmaceuticals, May 1, 2004, vol. 57, No. 3, pp. 441-446.
[cited by applicant]
Schwach G. et al: “Biodegradable microparticles for sustained release of a new GnRH antagonist-pa1i l: screening commercial PLGA and formulation technologies”, European Journal of Pharmaceutics and Biopharmaceutics, Els…
[cited by applicant]
SEER Program and the National Center for Health Statistics, <http://seer.cancer.gov/.> (2000: 2005).
[cited by applicant]
Sep. 26, 2022 PIV Letter (Redacted).
[cited by applicant]
Shahani et al., “Androgen Deprivation Therapy in Prostate Cancer and Metabolic Rick for Atherosclerosis,” 93 J. Clin Endocrinol Metab, pp. 2042-0249, 2008.
[cited by applicant]
Shahani et al., “Androgen deprivation therapy in prostate cancer and metabolic risk for atherosclerosis,” J. Clin. Endocrinol. Metab. 93(6):2402-2049 (Jun. 2008).
[cited by applicant]
Sharma et al., “To scale or not to scale: the principles of does extrapolation,” British Journal of Pharmacology, pp. 907-921, 2009.
[cited by applicant]
Shore et al., “Oral Relugolix for Androgen-Deprivation Therapy in Advanced Prostate Cancer,” N Engl J Med 382:2187-96 (2020).
[cited by applicant]
Shamdas et al., Leukoerythroblastic anemia in metastatic prostate cancer, Cancer 71(11):3594-3600 (1993).
[cited by applicant]
Smith et al., “Cardiovascular Safety of Degarelix: Results From a 12-Month, Comparative, Randomized, Open Label, Parallel Group Phase III Trial in Patients With Prostate Cancer,” 184 The Journal of Urology 2313-2319 (20…
[cited by applicant]
Smith, M.R. et al., “Gonadotropin-Releasing Hormone Blockers and Cardiovascular Disease Risk: Analysis of Prospective Clinical Trials of Degarelix,” 186 The Journal of Urology 1835-1842 (2011).
[cited by applicant]
Sorbera et al., “Degarelix Acetate”, GnRH Antagonist Prostate Cancer TI1erapy; Drugs of the Future 2006, vol. 31, No. 9, pp. 755-766.
[cited by applicant]
Spilker, Bert, “Guide to Cinical Trials,” (199.1) Raven Press, Ud., New York, ISBN 0-88167-767-1.
[cited by applicant]
Spilker, Bert, “Quality of Life and Pharmacoeconomics in Clinical Trials,” (1996) Lippincott—Raven Publishers, New York, ISBN 0-7817-0332-8.
[cited by applicant]
Steinberg, et al., “Degarelix: A Gonadotropin-Releasing Hormone Antagonist for the Management of Prostate Cancer,” Clinical Therapeutics, vol. 31, p 1s. 2312-2331, 2009.
[cited by applicant]
Stephens, M.D.B., “The Detection of New Adverse Drug Reactions,” (1988) Stockton Press, New York, ISBN 0-333-45417-0.
[cited by applicant]
Studer et al, Using PSA to Guide Timing of Androgen Deprivation in Patients with T0-4 N0-2 M0 Prostate Cancer not Suitable for Local Curative Treatment (EORTC 30891) Eur Urol, 53, 941-949, 2008.
[cited by applicant]
Szczepanska et al., “Efficient Method for the Concentration Determination of Fmoc Groups Incorporated in the Core-Shell Materials by Fmoc-Glycine,” Molecules 25:3983 (2020).
[cited by applicant]
Takeuchi et al., “Urinary pyridinoline and deoxypyridinoline as potential markers of bone metastasis in patients with prostate cancer,” J. Urol. 156:1691-1695 (1996).
[cited by applicant]
Tammela et al, “Degarelix—A Phase | Multicentre, Randomized Dose-escalating Study Testing a Novel GnRH Receptor Blocker in Prostate Cancer Patients,” Eur. Urol. Supp. 4(3), p. 228, 2005 (abstract 904).
[cited by applicant]
Tanriverdi et al., “Expression of Gonadotropin-Releasing Hormone Type-I (GnRH-I) and Type-II (GnRH-II) in human peripheral blood mononuclear cells (PBMCs) and regulation of B-Lymphoblastoid cell proliferation by GnRH-I …
[cited by applicant]
Tarnmela et al., “Degarelix—A Phase II Multicentre, Randomized Dose-escalating Study Testing a Novel GnRH Receptor Blocker in Prostate Cancer Patients,” Eur. Urol. Supp. 4(3), p. 288, 2005.
[cited by applicant]
Teal, et al., “Adverse Drug Experience Management: A Brief Review of the McNeil Pharmaceutical System,” (1985) Drug Info. J., vol. 19, pp. '17-25.
[cited by applicant]
The K-Zone, Biophysical data tables: standard man, Jul. 2004; printed Mar. 14, 2009 from www.kevinboone.com/biodat stdman.11tml; 1 page.
[cited by applicant]
The Practical Guide, Identification, Evaluation, and Treatment of Overweight and Obesity in Adults, NHLBI Obesity Education Initiative, National Institutes of Health, Oct. 2000.
[cited by applicant]
Thompson, et al., “Sudden Death to Disease Flare With Luteinizing Hormone-Releasing Hormone Agonist Therapy for Carcinoma of the Prostate,” J. Urol., CI 990) vol. 144, pp. 1479-1480.
[cited by applicant]
Tofteng et al., “Effect of Residual Water and Microwave Heating on the Half-Life of the Reagents and Reactive Intermediates in Peptide Synthesis” Journal of European Chemistry (2012).
[cited by applicant]
Tolis, G. et al, “Tumor growth inhibition in patients with prostatic carcinoma treated with luteinizing hormone-releasing hormone agonists”, PNAS (1982) 79:1685-1662.
[cited by applicant]
Tombal et al., “Determining the dose of degarelix for effective therapy of prostatecancer patients as investigated by the degarelix study groups,” Annals of Oncology vol. H (Supplement 9), pp. ix144-ix157, ix 150, 2006 …
[cited by applicant]
Torn0e et al., “Population Pharmacokinetic Modeling of a Subcutaneous Depot for GnRH Antagonist Degarelix,” Pharmaceutical Research, vol. 21, No. 4, pp. 574-584,2004.
[cited by applicant]
Tsai Henry K et al: Androgen deprivation therapy for localized prostate cancer and the risk of cardiovascular mortality., Journal of the National Cancer Institute Oct. 17, 2007 LNKD-PUBMED:17925537, vol. 99, No. 20, Oct…
[cited by applicant]
Tucci, et al. “Prognostic significance of disordered calcium metabolism in hormone-refractory prostate cancer patients wiUi metastatic bone disease”, Prostate Cancer and Prostatic Diseases (2009) 12:94-99.
[cited by applicant]
Turner, et al., “The Processing of Adverse Reactoin Reports at FDA,” ('1986) Drug. Inf. J., vol. 20, pp. 147-150.
[cited by applicant]
Van Kerrebroeck et al., “Desmopressin in the Treatment of Nocturia: A Double-Sine!, Placebo-Controlled Study”, European Urology, 52, (Jan. 16, 2007).
[cited by applicant]
Van Poppel et al., “A One-Year, Multicentre, Randomised Stucly of Degarelix a Gonaclatrophin-Releasing Hormone (GNRH) Receptor Blocker, in Prostate CancerPatients,” Eur Urol Supppl 2006:5(2):251.
[cited by applicant]
Van Poppel et al., “Degarelix: A Novel Gonadotropin-Releasing Horrnone (GnRH) Receptor Blocker-Results from a 1-yr, Multicentre, Randornised, Phase 2 Dosage-Finding Study in the Treatment of Prostate Cancer”, European U…
[cited by applicant]
Van Poppel et al., “Long-Term Evaluation of Degarelix, A gonadotrophin-Releasing Hormone (GNRH) Receptor Blocker, Investigated in a Multicentre Randomised Study in Prostate Cnacner (CAP) Patients,” Eur Urol. Suppl. 6(2)…
[cited by applicant]
Van Poppel et al., “Testosterone Surge: Rationale for Gonaclotropin-Releasing Hormone Blockers,” Urology 71(6):1001-06 (2008).
[cited by applicant]
Van Poppel, “Evaluation of degarelix in the management of prostate cancer,” Cancer Management and Research, vol. 2, pp. 39-52, Published online Jan. 25, 2010.
[cited by applicant]
Van Poppel, A One-Year, Multicentre, Randomised Study of Degarelix, a Gonadatrophin-Releasing Hormone (GNRH) Receptor Blocker, in Prostate Cancer Patients, Eur Urol Suppl 2006; 5(2):251 (abstract 915).
[cited by applicant]
Versuchsbericht Zerfallzeit Ursprunglicher Dateiname:D⋅ 13, Beigefugt als:Other-evidence-⋅1 (Jul. 23, 2014).
[cited by applicant]
Wiegel et al., Neoadjuvant Androgen Deprivation Therapy for Prostate Volume Reduction, Lower Urinary Tract Symptom Relief and Quality of Life Improvement in Men with Intermediate-High-Risk Prostate Cancer: A Randomised …
[cited by applicant]
Wiegel et al., “Neoadjuvant Androgen Deprivation Therapy for Prostate vol. Reduction, Lower Urinary Tract Symptom Relief and Quality of Life Improvement in Men with Intermediate-to High-risk Prostate Cancer: A Randomise…
[cited by applicant]
Wilson, et al., “Leuprolide acetate: a drug of diverse clinical applications,” Expert Opin. Investig. Drugs, (2007), vol. 16, pp. -i851-1863.
[cited by applicant]
Wilson, et al., “Prediction of Coronary Heart Disease Using Risk Factor Categories,” (1998) Circulation, 97:1837-47.
[cited by applicant]
Wolff et al., “Cumulative analysis from six comparative randomised clinical trials of degarelix versus luteinising hormone-releasing hormone (LHRH) agonists: Better PSA-progressionfree survival confirmed in trials an ev…
[cited by applicant]
Yannucci, et al., “The Effect of Androgen Deprivation Therapy on Fasting Serum Lipid and Glucose Parameters,” (2006) J. Urol., vol. 176, pp. 520-525.
[cited by applicant]
Ye Let al, “Bone metastasis in prostate cancer: Molecular and cellular mechanisms (Review),” International Journal of Molecular Medicine (2007) 20″ 103-111.
[cited by applicant]
Zacharakas, E. et al., “Salvage HIFU Effectively Reduces PSA in Patients with Biochemical Recurrence After Attempted Curative Treatment for Prostate Cancer,” Urology, vol. 70, pp. 83-84 (2007).
[cited by applicant]
Final Office Action received in U.S. Appl. No. 17/199,733 dated Jun. 21, 2024.
[cited by applicant]
Non-Final Office Action dated Jul. 30, 2025, in U.S. Appl. No. 17/199,733.
[cited by applicant]