IP Library Granted Patent US 12,371,481
Granted Patent B2
US 12,371,481 · App. 17/378,618 · Granted Jul 29, 2025

Methods for treating age-related macular degeneration

Inventors: Margarita Gekkieva (Basel, CH); Peter Sallstig (Summit, NJ); Werner Schmidt (Fort Worth, TX); James Warburton (Buckinghamshire, GB); Andreas Weichselberger (Basel, CH)
Assignee: Novartis AG
C07K16/22A61B3/12A61B5/4848A61K9/0048A61K39/3955A61K39/39591A61K2039/54A61K2039/545C07K2317/24C07K2317/52C07K2317/522C07K2317/56C07K2317/565C07K2317/567C07K2317/569C07K2317/622C07K2317/76C07K2317/94
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 12,371,481
App. No.
17/378,618
Granted
Jul 29, 2025
Kind
B2
Abstract

A method is provided for reducing the treatment burden for patients who have an intraocular neovascular disorder, the method comprising administering a therapeutically effective amount of VEGF antagonist on a dosing schedule that includes treatment intervals of 8 and/or 12 weeks.

Claims (21)

1. A method for treating age-related macular degeneration (AMD) in a patient in need thereof, the method comprising administering to the patient three individual doses of a VEGF antagonist at 4-week intervals, and thereafter administering to the patient an additional dose every 12 weeks or every 8 weeks, wherein each dose of the VEGF antagonist is at least 3 mg, wherein the VEGF antagonist is an anti-VEGF antibody comprising a variable heavy chain having the sequence as set forth in SEQ ID NO: 1 and a variable light chain having the sequence as set forth in SEQ ID NO: 2.

2. The method of claim 1 , wherein the VEGF antagonist is administered at 4-week intervals, and thereafter administering to the patient an additional dose every 12 weeks.

3. The method of claim 1 , wherein the VEGF antagonist is administered at 4-week intervals, and thereafter administering to the patient an additional dose every 8 weeks.

4. The method of claim 1 , wherein the VEGF antagonist is administered at 4-week intervals, and thereafter administering to the patient an additional dose every 12 weeks or every 8 weeks depending on the outcome of disease activity assessment, wherein the disease activity assessment includes determining the best-corrected visual acuity (BCVA), visual acuity (VA), central subfield thickness (CSFT) as measured by SD-OCT, and/or the presence of new or worsening intraretinal cysts/intraretinal fluid (IRC/IRF).

5. The method of claim 1 , wherein each dose of the VEGF antagonist is 3 mg.

6. The method of claim 1 , wherein each dose of the VEGF antagonist is 6 mg.

7. The method of claim 6 , wherein each dose of the VEGF antagonist is administered as a 50 μL intravitreal injection.

8. The method of claim 1 , wherein the VEGF antagonist comprises the sequence of SEQ ID NO: 3.

9. The method of claim 8 , wherein the VEGF antagonist is brolucizumab.

10. The method of claim 1 , wherein a 12-week treatment interval is switched to an 8-week treatment interval if the patient's disease activity is detected.

11. The method of claim 1 , wherein an 8-week treatment interval is switched to a 12-week treatment interval if the patient's disease activity is absent.

12. The method of claim 1 , wherein a 12-week treatment interval is switched to an 8-week treatment interval if the following criteria are met:

a) decrease in BCVA of ≥5 letters, due to nAMD disease activity, at Week 16 compared to Baseline,

b) decrease in BCVA of ≥5 letters, due to nAMD disease activity, at Week 16 compared to Week 12,

c) VA decline of ≥3 letters and CSFT increase ≥75 μm, at Week 16 compared to Week 12, and

d) new or worsening intraretinal cysts (IRC)/intraretinal fluid (IRF) at Week 16 compared to Week 12.

13. The method of claim 1 , wherein a 12-week treatment interval is switched to an 8-week treatment interval if the following criteria is met: decrease in BCVA of ≥5 letters, due to nAMD disease activity, at Week 20, 32, or 44 compared to Week 12.

14. The method of claim 1 , wherein a 12-week treatment interval is switched to an 8-week treatment interval if the following criteria is met: decrease in BCVA of ≥5 letters, due to nAMD disease activity, at Week 56, 68, or 80 compared to Week 12.

15. The method of claim 11 , wherein an 8-week treatment interval is switched to a 12-week treatment interval if the following criteria are not met:

a) decrease in BCVA of ≥5 letters, due to nAMD disease activity, at Week 48 compared to Week 32, and

b) new or worsening intraretinal cysts (IRC)/intraretinal fluid (IRF) at Week 48 compared to Week 32.

Assignments (5)
CORRECTIVE ASSIGNMENT TO CORRECT THE TYPO ON PAGE 1, PARAGRAPH 3, LINE 5, ENTITY ALCON LABORATORIES SHOULD BE NOVARTIS PHARMA AG PREVIOUSLY RECORDED ON REEL 59638 FRAME 339. ASSIGNOR(S) HEREBY CONFIRMS THE ASSIGNMENT. Recorded Dec 9, 2025
From: GEKKIEVA, MARGARITA; WARBURTON, JAMES; WEICHSELBERGER, ANDREAS
To: NOVARTIS PHARMA AG
Reel/Frame 073978/0195 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 19, 2022
From: SALLSTIG, PETER; SCHMIDT, WERNER
To: ALCON RESEARCH, LTD.
Reel/Frame 059637/0886 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 19, 2022
From: GEKKIEVA, MARGARITA; WARBURTON, JAMES; WEICHSELBERGER, ANDREAS
To: NOVARTIS PHARMA AG
Reel/Frame 059638/0339 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 19, 2022
From: ALCON RESEARCH, LTD.
To: NOVARTIS AG
Reel/Frame 059638/0441 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 19, 2022
From: NOVARTIS PHARMA AG
To: NOVARTIS AG
Reel/Frame 059640/0683 →
Continuity (5)
Division 16018244 · Jun 26, 2018
Division 14934731 · Nov 6, 2015
Provisional Application 62088061 · Dec 5, 2014
Provisional Application 62076770 · Nov 7, 2014
Related Publication 20210340242A1 · Nov 4, 2021
References Cited (66)
US 8293235B2 · Borras et al. · 2012 [cited by applicant]
US 8349322B2 · Borras et al. · 2013 [cited by applicant]
US 8673310B2 · Borras et al. · 2014 [cited by applicant]
US 8937162B2 · Borras et al. · 2015 [cited by applicant]
US 9090684B2 · Borras et al. · 2015 [cited by applicant]
US 9422366B2 · Borras et al. · 2016 [cited by applicant]
US 9593161B2 · Borras et al. · 2017 [cited by applicant]
US 9873737B2 · Borras et al. · 2018 [cited by applicant]
US 10035850B2 · Gekkieva et al. · 2018 [cited by applicant]
US 10087244B2 · Borras et al. · 2018 [cited by applicant]
US 10100111B2 · Borras et al. · 2018 [cited by applicant]
US 10590193B2 · Borras et al. · 2020 [cited by applicant]
US 10689438B2 · Zhang et al. · 2020 [cited by applicant]
US 20180127493A1 · Borras et al. · 2018 [cited by applicant]
US 20180371074A1 · Borras et al. · 2018 [cited by applicant]
US 20200172608A1 · Borras et al. · 2020 [cited by applicant]
US 20200190179A1 · Sigg et al. · 2020 [cited by applicant]
US 20200270336A1 · Zhang et al. · 2020 [cited by applicant]
US 20210017266A1 · Racine et al. · 2021 [cited by applicant]
EP 2311433A2 · 2011 [cited by applicant]
WO 2007011873A2 · 2007 [cited by applicant]
WO 2009155724A2 · 2009 [cited by applicant]
WO 2010006454A2 · 2010 [cited by applicant]
WO 2012097019A1 · 2012 [cited by applicant]
WO 2013166436A1 · 2013 [cited by applicant]
WO 2015086830A1 · 2015 [cited by applicant]
Anonymous/Drugspider. http://drugspider.com/drug/brolucizumab, retrieved on Nov. 7, 2016. (Year: 2016). [cited by examiner]
Anonymous, “Monthly and As-Needed Treatment in the SHORE Study Resulted in Similar Visual Acuity Gains in RVO”, Retina Today, Sep. 2014, pp. 14-17. [cited by applicant]
Anonymous-Broluciziumab (available on the internet at http://drugspider.com/drug/brolucizumab, retrieved on Nov. 7, 2016). [cited by applicant]
Chuprov et al., Visual acuity at intermediate distance after implantation of different models of intraocular lenses, Kazan Medical Journal, 2012, 458-460, 93-3. [cited by applicant]
Clinical Trial NCT04287348, Aug. 14, 2021, http:/clinicaltrials.gov. [cited by applicant]
Clinical Trial NCT04662944, Feb. 10, 2021, http://clinicaltrials.gov. [cited by applicant]
Clinical Trial NCT04679935, Feb. 2, 2021, http://clinicaltrials.gov. [cited by applicant]
Dugel et al., Hawk and Harrier: Phase 3, Multicenter, Randomized, Double-Masked Trials of Brolucizumab for Neovascular Age-Related Macular Degeneration, Ophthalmology, Apr. 12, 2019, pp. 72-84, vol. 127, No. 1. [cited by applicant]
Jeffrey S. Heier, “Intravitreal Aflibercept for AMD: 2-year results”, Retina Today, Mar. 2012, pp. 49-51. [cited by applicant]
Mantel et al., Reducing the Clinical Burden of ranibizumab treatment for neovascular age-related macular degeneration using an individually planned regimen, British Journal of Ophthalmology, Apr. 2014, 1192-1196, vol. 9… [cited by applicant]
Pravin Dugel, Results of ESBA 1008, a single-chain antibody fragment, for the treatment of neovascular AMD, American Society of Retina Specialists Annual Meeting, 2014. [cited by applicant]
Pravin U. Dugel, Novel molecule shows promise for future treatment of neovascular AMD, American Society of Retina Specialists Meeting, Aug. 11, 2014. [cited by applicant]
Tolentino et al., Drugs in Phase II clinical trials for the treatment of age-related macular degeneration, Expert Opinion on Investigational drugs, 2015, 183-199, 24-2. [cited by applicant]
Yannuzzi Nicolas et al., Brolucizumab: evidence to date in the treatment of neovascular age-related macular degeneration, Clinical Ophthalmology, 2019, 1323-1329, 13, Dove Medical Press Limited. [cited by applicant]
Clinical Trial NCT04597632, Oct. 22, 2020, http://clinicaltrials.gov. [cited by applicant]
Clinical Trial NCT04543331, Sep. 10, 2020, http://clinicaltrials.gov. [cited by applicant]
Clinical Trial NCT04047472, Aug. 6, 2019, http://clinicaltrials.gov. [cited by applicant]
Clinical Trial NCT01796964, Feb. 22, 2013, http://clinicaltrials.gov. [cited by applicant]
Clinical Trial NCT01304693, Feb. 25, 2011, http://clinicaltrials.gov. [cited by applicant]
Clinical Trial NCT01849692, May 8, 2013, http://clinicaltrials.gov. [cited by applicant]
Clinical Trial NCT02434328, May 5, 2015, http://clinicaltrials.gov. [cited by applicant]
Clinical Trial NCT02307682, Dec. 4, 2014, http://clinicaltrials.gov. [cited by applicant]
Clinical Trial NCT02507388, Jul. 23, 2015, http:/clinicaltrials.gov. [cited by applicant]
Clinical Trial NCT03954626, May 17, 2019, http://clinicaltrials.gov. [cited by applicant]
Clinical Trial NCT04264819, Feb. 11, 2020, http://clinicaltrials.gov. [cited by applicant]
Clinical Trial NCT04239027, Jan. 23, 2020, http://clinicaltrials.gov. [cited by applicant]
Clinical Trial NCT03930641, Apr. 29, 2019, http://clinicaltrials.gov. [cited by applicant]
Clinical Trial NCT04005352, Jul. 2, 2019, http://clinicaltrials.gov. [cited by applicant]
Clinical Trial NCT04278417, Feb. 20, 2020, http://clinicaltrials.gov. [cited by applicant]
Clinical Trial NCT04058067, Aug. 15, 2019, http://clinicaltrials.gov. [cited by applicant]
Clinical Trial NCT03710564, Oct. 18, 2018, http://clinicaltrials.gov. [cited by applicant]
Clinical Trial NCT03386474, Dec. 29, 2017, http://clinicaltrials.gov. [cited by applicant]
Clinical Trial NCT04079231, Sep. 6, 2019, http://clinicaltrials.gov. [cited by applicant]
Clinical Trial NCT03917472, Apr. 17, 2019, http://clinicaltrials.gov. [cited by applicant]
Clinical Trial NCT03481660, Mar. 29, 2018, http://clinicaltrials.gov. [cited by applicant]
Clinical Trial NCT03481634, Mar. 29, 2018, http://clinicaltrials.gov. [cited by applicant]
Clinical Trial NCT03810313, Jan. 18, 2019, http:/clinicaltrials.gov. [cited by applicant]
Clinical Trial NCT03802630, Jan. 14, 2019, http://clinicaltrials.gov. [cited by applicant]
Clinical Trial NCT05112835, Nov. 9, 2021, http://clinicaltrials.gov. [cited by applicant]
Veritti et al., “Neovascular age-related macular degeneration”, Ophthalmologica, Apr. 24, 2012, 227 (Suppl 1), pp. 11-20, DOI: 10.1159/000337154. [cited by applicant]