Granted Patent
B2
US 12,404,337 · App. 18/391,233 · Granted Sep 2, 2025
Compositions, doses, and methods for treatment of thyroid eye disease
Assignee:
Viridian Therapeutics, Inc.
C07K16/2863A61P5/14A61P27/02A61P37/00A61K2039/505A61K2039/54A61K2039/545C07K2317/21C07K2317/24C07K2317/565C07K2317/76C07K2317/77C07K2317/92
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Abstract
Antibodies and compositions against IGF-1R and uses thereof are provided herein.
Claims (13)
1. A method of treating active thyroid eye disease (TED) in a subject in need thereof, the method comprising:
administering a first dose of a pharmaceutical composition comprising an anti-IGF-IR antibody at 10 mg/kg, and
administering a subsequent dose of the pharmaceutical composition comprising the anti-IGF-1R antibody at 10 mg/kg three weeks after the first dose, such that the subject has a reduction in proptosis or an improvement in CAS score within 6 weeks of the first dose,
wherein administration of the antibody is by intravenous infusion,
wherein the anti-IGF-1R antibody comprises a light chain and a heavy chain, and
wherein the heavy chain comprises a HCDR1 of SEQ ID NO: 7, a HCDR2 of SEQ ID NO: 8, and a HCDR3 of SEQ ID NO: 9 and the light chain comprises a LCDRI of SEQ ID NO: 4,a LCDR2 of SEQ ID NO: 5 and a LCDR3 of SEQ ID NO: 6.
2. The method of claim 1 , wherein the light chain comprises a variable region having the amino acid sequence of SEQ ID NO: 2 and the heavy chain comprises a variable region sequence having the amino acid sequence of SEQ ID NO: 3.
3. The method of claim 2 , wherein the light chain comprises an amino acid sequence of SEQ ID NO: 11, and the heavy chain comprises an amino acid sequence of SEQ ID NO: 10.
4. The method of claim 1 , wherein the antibody is administered by intravenous infusion over 45 minutes to about 90 minutes.
5. The method of claim 1 , wherein the CAS score has an improvement of at least −2.
6. The method of claim 1 , wherein the antibody is administered by intravenous infusion over 60 minutes to about 90 minutes.
7. The method of claim 1 , wherein the CAS score has an improvement of at least −3.
8. The method of claim 1 , wherein the CAS score has an improvement of at least −4.
Assignments (2)
INTELLECTUAL PROPERTY SECURITY AGREEMENT
Recorded Oct 20, 2025
From: VIRIDIAN THERAPEUTICS, INC.
To: HERCULES CAPITAL, INC., AS AGENT
Reel/Frame 073121/0769 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Feb 6, 2024
From: O'SHAUGHNESSY, DENIS; KATZ, BARRETT
To: VIRIDIAN THERAPEUTICS, INC.
Reel/Frame 066394/0579 →
Continuity (4)
Provisional Application
63261744
· Sep 28, 2021
Provisional Application
63260133
· Aug 10, 2021
References Cited (292)
US 4439196A
· Higuchi
· 1984
[cited by applicant]
US 4447224A
· Decant et al.
· 1984
[cited by applicant]
US 4447233A
· Mayfield
· 1984
[cited by applicant]
US 4487603A
· Harris
· 1984
[cited by applicant]
US 4596556A
· Morrow et al.
· 1986
[cited by applicant]
US 4790824A
· Morrow et al.
· 1988
[cited by applicant]
US 4816567A
· Cabilly et al.
· 1989
[cited by applicant]
US 4941880A
· Burns
· 1990
[cited by applicant]
US 4949778A
· Saito et al.
· 1990
[cited by applicant]
US 5064413A
· Mckinnon et al.
· 1991
[cited by applicant]
US 5260203A
· Ladner et al.
· 1993
[cited by applicant]
US 5312335A
· Mckinnon et al.
· 1994
[cited by applicant]
US 5383851A
· Mckinnon et al.
· 1995
[cited by applicant]
US 5399163A
· Peterson et al.
· 1995
[cited by applicant]
US 5475096A
· Gold et al.
· 1995
[cited by applicant]
US 5831012A
· Nilsson et al.
· 1998
[cited by applicant]
US 6004746A
· Brent et al.
· 1999
[cited by applicant]
US 6005079A
· Casterman et al.
· 1999
[cited by applicant]
US 6096002A
· Landau
· 2000
[cited by applicant]
US 6620135B1
· Weston et al.
· 2003
[cited by applicant]
US 6794144B1
· Saksela et al.
· 2004
[cited by applicant]
US 6818418B1
· Lipovsek et al.
· 2004
[cited by applicant]
US 6994982B1
· Watt et al.
· 2006
[cited by applicant]
US 7083784B2
· Dall et al.
· 2006
[cited by applicant]
US 7166697B1
· Galanis et al.
· 2007
[cited by applicant]
US 7186524B2
· Kolmar et al.
· 2007
[cited by applicant]
US 7250297B1
· Beste et al.
· 2007
[cited by applicant]
US 7417130B2
· Stumpp et al.
· 2008
[cited by applicant]
US 7572897B2
· Graus et al.
· 2009
[cited by applicant]
US 7670600B2
· Dall et al.
· 2010
[cited by applicant]
US 7803907B2
· Stemmer et al.
· 2010
[cited by applicant]
US 7838629B2
· Fiedler et al.
· 2010
[cited by applicant]
US 7998681B2
· Smith et al.
· 2011
[cited by applicant]
US 8137933B2
· Saha
· 2012
[cited by applicant]
US 8153121B2
· Smith et al.
· 2012
[cited by applicant]
US 8394925B2
· Chamberlain et al.
· 2013
[cited by applicant]
US 8951790B2
· Saha
· 2015
[cited by applicant]
US 9045536B2
· Merchant et al.
· 2015
[cited by applicant]
US 9982036B2
· Bossenmaier et al.
· 2018
[cited by applicant]
US 20040023334A1
· Prior
· 2004
[cited by applicant]
US 20040132094A1
· Etzerodt et al.
· 2004
[cited by applicant]
US 20040146938A1
· Nguyen et al.
· 2004
[cited by applicant]
US 20040157209A1
· Yilmaz et al.
· 2004
[cited by applicant]
US 20040202651A1
· Cohen et al.
· 2004
[cited by applicant]
US 20040209243A1
· Nixon et al.
· 2004
[cited by applicant]
US 20060286103A1
· Kolhe et al.
· 2006
[cited by applicant]
US 20070041972A1
· Rother et al.
· 2007
[cited by applicant]
US 20080014203A1
· Hansen et al.
· 2008
[cited by applicant]
US 20080112888A1
· Wang
· 2008
[cited by applicant]
US 20080226635A1
· Koll et al.
· 2008
[cited by applicant]
US 20090275126A1
· Graus et al.
· 2009
[cited by applicant]
US 20100104645A1
· Ali et al.
· 2010
[cited by applicant]
US 20100119446A1
· Grabulovski et al.
· 2010
[cited by applicant]
US 20100143340A1
· Kolhe et al.
· 2010
[cited by applicant]
US 20100260668A1
· Ghayur et al.
· 2010
[cited by applicant]
US 20110014117A1
· Wang et al.
· 2011
[cited by applicant]
US 20110014207A1
· Gualberto et al.
· 2011
[cited by applicant]
US 20110044980A1
· Ghayur et al.
· 2011
[cited by applicant]
US 20110229933A1
· Krishnan et al.
· 2011
[cited by applicant]
US 20110263827A1
· Ghayur et al.
· 2011
[cited by applicant]
US 20120014957A1
· Ghayur et al.
· 2012
[cited by applicant]
US 20120076778A1
· Koll et al.
· 2012
[cited by applicant]
US 20120100166A1
· Roschke et al.
· 2012
[cited by applicant]
US 20120201746A1
· Liu et al.
· 2012
[cited by applicant]
US 20120237507A1
· Bossenmaier et al.
· 2012
[cited by applicant]
US 20120263722A1
· Ghayur et al.
· 2012
[cited by applicant]
US 20130004416A1
· Wu et al.
· 2013
[cited by applicant]
US 20130195871A1
· Ghayur et al.
· 2013
[cited by applicant]
US 20130259868A1
· Roschke et al.
· 2013
[cited by applicant]
US 20140050729A1
· Yao
· 2014
[cited by applicant]
US 20140079665A1
· Goetsch et al.
· 2014
[cited by applicant]
US 20150017168A1
· Ghayur et al.
· 2015
[cited by applicant]
US 20150056191A1
· Sathyanarayanan et al.
· 2015
[cited by applicant]
US 20150168424A1
· Wang
· 2015
[cited by applicant]
US 20160060299A1
· Luesch
· 2016
[cited by applicant]
US 20160096894A1
· Cohen et al.
· 2016
[cited by applicant]
US 20160151487A1
· Hartmann et al.
· 2016
[cited by applicant]
US 20170218091A1
· Ambrosi
· 2017
[cited by applicant]
US 20180243432A1
· Poma et al.
· 2018
[cited by applicant]
US 20210253719A1
· Sherman
· 2021
[cited by examiner]
US 20210284741A1
· Madden et al.
· 2021
[cited by applicant]
US 20220088231A1
· Burak et al.
· 2022
[cited by applicant]
US 20220235137A1
· Bedian et al.
· 2022
[cited by applicant]
US 20220267450A1
· Bedian et al.
· 2022
[cited by applicant]
US 20220267451A1
· Bedian et al.
· 2022
[cited by applicant]
US 20220275096A1
· Bedian et al.
· 2022
[cited by applicant]
US 20230002495A1
· Bedian et al.
· 2023
[cited by applicant]
US 20230084477A1
· O'shaughnessy et al.
· 2023
[cited by applicant]
US 20240043546A1
· Bedian et al.
· 2024
[cited by applicant]
US 20240343814A1
· Bedian et al.
· 2024
[cited by applicant]
US 20240352133A1
· Bedian et al.
· 2024
[cited by applicant]
US 20240360227A1
· Bedian et al.
· 2024
[cited by applicant]
US 20240368282A1
· Schlegel et al.
· 2024
[cited by applicant]
US 20250099583A1
· Huyghe et al.
· 2025
[cited by applicant]
CN 101229371A
· 2008
[cited by applicant]
CN 101292036A
· 2008
[cited by applicant]
CN 113402602A
· 2021
[cited by applicant]
EP 0404097A2
· 1990
[cited by applicant]
EP 1399483B1
· 2010
[cited by applicant]
EP 1689782B1
· 2010
[cited by applicant]
EP 2235059A1
· 2010
[cited by applicant]
EP 1959014B1
· 2011
[cited by applicant]
EP 2230254B1
· 2013
[cited by applicant]
EP 2681239B1
· 2015
[cited by applicant]
EP 2032989B2
· 2015
[cited by applicant]
EP 2681240B1
· 2017
[cited by applicant]
EP 2194067B1
· 2017
[cited by applicant]
EP 2863947B1
· 2018
[cited by applicant]
EP 2714733B1
· 2019
[cited by applicant]
EP 1469879B1
· 2019
[cited by applicant]
EP 2970433B1
· 2019
[cited by applicant]
EP 2814500B1
· 2020
[cited by applicant]
EP 2322550B1
· 2020
[cited by applicant]
EP 3458101B1
· 2020
[cited by applicant]
TW 202228775A
· 2022
[cited by applicant]
WO 8801649A1
· 1988
[cited by applicant]
WO 9311161A1
· 1993
[cited by applicant]
WO 9404678A1
· 1994
[cited by applicant]
WO 9425591A1
· 1994
[cited by applicant]
WO 03100008A2
· 2003
[cited by applicant]
WO 03106621A2
· 2003
[cited by applicant]
WO 2006060419A2
· 2006
[cited by applicant]
WO 2007062037A2
· 2007
[cited by applicant]
WO 2008005469A2
· 2008
[cited by applicant]
WO 2008076278A2
· 2008
[cited by applicant]
WO 2008079849A2
· 2008
[cited by applicant]
WO 2011028811A2
· 2011
[cited by applicant]
WO 2011161119A1
· 2011
[cited by applicant]
WO 2014177459A2
· 2014
[cited by applicant]
WO 2016064716A1
· 2016
[cited by applicant]
WO 2017011773A2
· 2017
[cited by applicant]
WO 2019084026A1
· 2019
[cited by applicant]
WO 2019084030A1
· 2019
[cited by applicant]
WO 2019173352A1
· 2019
[cited by applicant]
WO 2019183523A1
· 2019
[cited by applicant]
WO 2020006486A1
· 2020
[cited by applicant]
WO 2020132091A2
· 2020
[cited by applicant]
WO 2021041773A1
· 2021
[cited by applicant]
WO WO2021041773
· 2021
[cited by examiner]
WO WO2021243014
· 2021
[cited by examiner]
WO 2022081799A1
· 2022
[cited by applicant]
WO 2022081804A1
· 2022
[cited by applicant]
WO 2022187510A1
· 2022
[cited by applicant]
WO 2023001917A1
· 2023
[cited by applicant]
WO 2023019171A1
· 2023
[cited by applicant]
WO 2023122714A2
· 2023
[cited by applicant]
WO 2023133485A2
· 2023
[cited by applicant]
WO 2023133486A2
· 2023
[cited by applicant]
WO 2023133561A1
· 2023
[cited by applicant]
WO 2025014774A1
· 2025
[cited by applicant]
Smith et al., N Engl J Med. May 4, 2017; 376(18): 1748-1761.
[cited by examiner]
International Search Report for PCT/US2021/054907 dated Feb. 23, 2022 (5 pages).
[cited by applicant]
International Search Report for PCT/US2021/054914 dated Feb. 23, 2022 (6 pages).
[cited by applicant]
International Search Report for PCT/US2022/074764 dated Nov. 4, 2022 (4 pages).
[cited by applicant]
International Search Report for PCT/US2022/082214 dated Jul. 3, 2023 (6 pages).
[cited by applicant]
International Search Report for PCT/US2023/060206 dated Jun. 21, 2023 (5 pages).
[cited by applicant]
International Search Report for PCT/US2023/060207 dated Jun. 30, 2023 (5 pages).
[cited by applicant]
International Search Report for PCT/US2024/036800 dated Dec. 12, 2024 (7 pages).
[cited by applicant]
International Search Report for PCT/US2024/036803 dated Dec. 12, 2024 (8 pages).
[cited by applicant]
International Search Report for PCT/US2024/045630 dated Jan. 27, 2025 (5 pages).
[cited by applicant]
International Search Report for PCT/US2024/060579 dated Apr. 3, 2025 (6 pages).
[cited by applicant]
International Search Report for PCT/US2025/010700 dated Apr. 24, 2025 (5 pages).
[cited by applicant]
Partial Search Report for PCT/US2024/036800 dated Oct. 21, 2024 (13 pages).
[cited by applicant]
Partial Search Report for PCT/US2024/036803 dated Oct. 21, 2024 (30 pages).
[cited by applicant]
Partial Search Report for PCT/US2025/010706 dated May 13, 2025 (11 pages).
[cited by applicant]
Partial Search Report for PCT/US2025/010718 dated May 12, 2025 (34 pages).
[cited by applicant]
“A Randomized, Active Controlled, Safety and Tolerability Study of VRDN-001 in Participants With Thyroid Eye Disease (TED)”, ClinicalTrials.gov, U.S. National Library of Medicine, May 23, 2024, NCT06384547 (8 pages).
[cited by applicant]
“A Safety, Tolerability and Efficacy Study of Veligrotug (VRDN 001) in Healthy Volunteers and Participants with Thyroid Eye Disease (TED) (THRIVE)”, ClinicalTrials.gov, U.S. National Library of Medicine, Dec. 3, 2021, N…
[cited by applicant]
“A Study Evaluating TEPEZZA® Treatment in Patients With Chronic (Inactive) Thyroid Eye Disease”, ClinicalTrials.gov, U.S. National Library of Medicine, Oct. 12, 2020, NCT04583735, (9 pages).
[cited by applicant]
“An Efficacy, Safety, and Tolerability Study of Veligrotug (VRDN-001), in Participants with Chronic Thyroid Eye Disease (TED)”, ClinicalTrials.gov, U.S. National Library of Medicine, Nov. 14, 2023, NCT06021054 (9 pages).
[cited by applicant]
“Anti-insulin-like Growth Factor-1 Receptor (IGF-1R) Antibodies in Graves' Disease and Graves' Orbitopahty (IGF1RAbsGO)”, ClinicalTrials.gov, U.S. National Library of Medicine, Apr. 13, 2018, NCT03498417, (7 pages).
[cited by applicant]
“Expanded Access Protocol of Teprotumumab (HZN-001) for Patients With Active Thyroid Eye Disease (EAP)”, ClinicalTrials.gov, U.S. National Library of Medicine, Aug. 1, 2019, NCT04040894, (7 pages).
[cited by applicant]
“International Nonproprietary Names for Pharmaceutical Substances (INN)”, Who Drug Information, vol. 22, No. 4, Jan. 1, 2008 URL: https://cdn.who.int/media/docs/default-source/international-nonproprietary-names-(inn)/pl…
[cited by applicant]
“Teprotumumab (RV 001) Treatment in Patient with Active Thyroid Eye Disease”, Clinicaltrials.gov, U.S. National Library of Medicine, Jun. 5, 2013, NCT01868997 (9 pages).
[cited by applicant]
“Treatment of Graves' Orbitopathy (Thyroid Eye Disease) to Reduce Proptosis With Teprotumumab Infusions in a Randomized, Placebo-Controlled, Clinical Study (OPTIC)”, ClinicalTrials.gov, U.S. National Library of Medicine…
[cited by applicant]
“Treatment of Graves' Orbitopathy to Reduce Proptosis With Teprotumumab Infusions in an Open-Label Clinical Extension Study (OPTIC-X)”, ClinicalTrials.gov, U.S. National Library of Medicine, Mar. 9, 2018, NCT03461211, (…
[cited by applicant]
Allen, Richard C., et al., “A Perspective on the Current Role of Teprotumumab in Treatment of Thyroid Eye Disease”, American Academy of Ophthalmology, vol. 128, No. 8, Aug. 2021, pp. 1125-1128, DOI: 10.1016/j.ophtha.202…
[cited by applicant]
Baert, Filip , et al., “Influence of Immunogenicity on the Long-Term Efficacy of Infliximab in Crohn's Disease”, The New England Journal of Medicine, vol. 348, 2003, pp. 601-608, DOI: 10.1056/NEJMoa020888, (8 pages).
[cited by applicant]
Beniaminovitz, Ainat , et al., “Prevention of Rejection in Cardiac Transplantation by Blockade of the Interleukin-2 Receptor with a Monoclonal Antibody”, The New England Journal of Medicine, vol. 342, 2000, pp. 613-619,…
[cited by applicant]
Chen, Hong , et al., “Teprotumumab, an IGF-1R Blocking Monoclonal Antibody Inhibits TSH and IGF-1 Action in Fibrocytes”, Journal of Clinical Endocrinology and Metabolism, vol. 99, No. 9, Sep. 1, 2014, pp. E1635-E1640, D…
[cited by applicant]
Chiou, Carolina A., et al., “Teprotumumab for the treatment of mild compressive optic neuropathy in thyroid eye disease: A report of two cases”, American Journal of Ophthalmology Case Reports, vol. 22, Jun. 2021, 101075…
[cited by applicant]
Chothia, Cyrus , et al., “Canonical structures for the hypervariable regions of immunoglobulins”, Journal of Molecular Biology, vol. 196, No. 4, Aug. 20, 1987, pp. 901-917, DOI: 10.1016/0022-2836(87)90412-8, (18 pages).
[cited by applicant]
Chothia, Cyrus , et al., “Conformations of immunoglobulin hypervariable regions”, Nature, vol. 342, Dec. 1989, pp. 877-883, DOI: 10.1038/342877a0, (7 pages).
[cited by applicant]
Cui, Xuejiao , et al., “A review of TSHR- and IGF-1R-related pathogenesis and treatment of Graves; orbitopathy”, Frontiers in Immunology, vol. 19, Jan. 19, 2023 (12 pages).
[cited by applicant]
Dall'acqua, William F., et al., “Properties of human lgG1 s engineered for enhanced binding to the neonatal Fe receptor (FcRn)”, Journal of Biological Chemistry, vol. 281, No. 33, Jun. 21, 2006 (pp. 23514-23524).
[cited by applicant]
Diniz, Stefania B., et al., “Early Experience With the Clinical Use of Teprotumumab in a Heterogenous Thyroid Eye Disease Population”, Ophthalmic Plastic and Reconstructive Surgery, vol. 37, No. 6, 2021, pp. 583-591, DO…
[cited by applicant]
Dolgin, Elie , “IGF-1R drugs travel from cancer cradle to Graves”, Nature Biotechnology, vol. 38, 2020, pp. 385-388, DOI: 10.1038/s41587-020-0481-8, (4 pages).
[cited by applicant]
Dosiou, Chrysoula , et al., “Thyroid Eye Disease: Navigating the New Treatment Landscape”, Journal of the Endocrine Society, vol. 5, No. 5, 2021, Author Manuscript (40 pages).
[cited by applicant]
Douglas, Raymond S., et al., “Aberrant Expression of the Insulin-Like Growth Factor-1 Receptor by T Cells from Patients with Graves' Disease May Carry Functional Consequences for Disease Pathogenesis”, The Journal of Im…
[cited by applicant]
Douglas, Raymond S., et al., “B Cells from Patients with Graves' Disease Aberrantly Express the IGF-1 Receptor: Implications for Disease Pathogenesis”, The Journal of Immunology, vol. 181, No. 8, 2008, pp. 5768-5774, DO…
[cited by applicant]
Douglas, Raymond S., et al., “Teprotumumab for the Treatment of Active Thyroid Eye Disease”, The New England Journal of Medicine, vol. 382, No. 4, 2020, pp. 341-352, DOI: 10.1056/NEJMoa1910434, (12 pages).
[cited by applicant]
Douglas, Raymond S., “Teprotumumab, an insulin-like growth factor-1 receptor antagonist antibody, in the treatment of active thyroid eye disease: a focus on proptosis”, Eye, vol. 33, 2019, pp. 183-190, DOI: 10.1038/s414…
[cited by applicant]
Edmunds, Matthew Ross, “Investigation of Candidate Biomarkers in Graves' Disease and Thyroid-Associated Ophthalmopathy”, University of Birmingham, 2016, (306 pages).
[cited by applicant]
Foster, Kelly , et al., “6461 VRDN-003, A Full Antagonist Antibody To The IGF-1 Receptor For Thyroid Eye Disease (TED): Safety And Pharmacokinetic Results Of Subcutaneous Administration In Healthy Volunteers”, Abstract,…
[cited by applicant]
Foster, Kelly , et al., “Thyroid FRI546 VRDN-001, A Full Antagonist Antibody To IGF-1 Receptor In Development For Thyroid Eye Disease (TED): Pharmacodynamic Responses In Healthy Volunteers And Patients With Active TED”,…
[cited by applicant]
Ghosh, Subrata , et al., “Natalizumab for Active Crohn's Disease”, The New England Journal of Medicine, vol. 348, No. 1, Jan. 2, 2003, pp. 24-32, DOI: 10.1056/NEJMoa020732, (9 pages).
[cited by applicant]
Gualberto A., et al., “Emerging role of insulin-like growth factor receptor inhibitors in oncology: early clinical trial results and future directions”, Oncogene, vol. 28, No. 34, 2009, pp. 3009-3021, DOI:10.1038/onc.20…
[cited by applicant]
Herold, Kevan C., et al., “Anti-CD3 Monoclonal Antibody in New-Onset Type 1 Diabetes Mellitus”, The New England Journal of Medicine, vol. 346, No. 22, May 30, 2002, pp. 1692-1698, DOI: 10.1056/NEJMoa012864, (7 pages).
[cited by applicant]
Hoa, Neil , et al., “Nuclear Targeting of IGF-1 Receptor in Orbital Fibroblasts from Graves' Disease: Apparent Role of ADAM17”, PLoS One, vol. 7, No. 4, Apr. 2012, e34173, DOI: 10.1371/journal.pone.0034173, (9 pages).
[cited by applicant]
Holliger, Philipp , et al., ““Diabodies”: small bivalent and bispecific antibody fragments”, Proceedings of the National Academy of Sciences, vol. 90, No. 14, 1993, pp. 6444-6448, (5 pages).
[cited by applicant]
Holliger, Philipp , et al., “Engineered antibody fragments and the rise of single domains”, Nature Biotechnology, vol. 23, No. 9, 2005, pp. 1126-1136, DOI: 10.1038/nbt1142, (12 pages).
[cited by applicant]
Jain, Amy Patel, “Teprotumumab reduces extraocular muscle and orbital fat volume in thyroid eye disease”, British Journal of Ophthalmology, vol. 106, No. 2, 2020, pp. 1-7, DOI: 10.1136/bjophthalmol-2020-317806, (7 pages…
[cited by applicant]
Janssen, Joseph A.M.J.L., et al., “Lessons Learned from Targeting IGF-I Receptor in Thyroid-Associated Ophthalmopathy”, Cell, vol. 10, No. 2, 2021, 383, DOI: 10.3390/cells10020383, (17 pages).
[cited by applicant]
Kabat, Elvin A., et al., “Unusual distributions of amino acids in complementarity determining (hypervariable) segments of heavy and light chains of immunoglobulins and their possible roles in specificity of antibody-com…
[cited by applicant]
Kahaly, George J, “Management of Graves Thyroidal and Extrathyroidal Disease: An Update”, The Journal of Clinical Endocrinology & Metabolism, vol. 105, No. 12, Dec. 2020, pp. 3704-3720, DOI: 10.1210/clinem/dgaa646, (17 …
[cited by applicant]
Kamboj , et al., “Emerging Therapies in the Medical Management of Thyroid Eye Disease”, Frontiers in Ophthalmology, vol. 3, 1295902, Dec. 12, 2023, DOI:10.3389/fopht.2023.1295902 (5 pages).
[cited by applicant]
Keenan, Gregory F., et al., “A First-in-Human Phase 1 Randomized, Single-Ascending Dose Study of Lonigutamab, an Anit-IGF-1R Monoclonal Antibody, in Healthy Volunteers”, Poster Presentation, 49th North American Neuro-Op…
[cited by applicant]
Krieger, Christine C., et al., “Bidirectional TSH and IGF-1 Receptor Cross Talk Mediates Stimulation of Hyaluronan Secretion by Graves' Disease Immunoglobins”, The Journal of Clinical Endocrinology & Metabolism, vol. 10…
[cited by applicant]
Krieger, Christine C., et al., “Is There Evidence for IGF1R-Stimulating Abs in Graves' Orbitopathy Pathogenesis?”, International Journal of Molecular Sciences, vol. 21, No. 18, 2020, 6561, DOI: 10.3390/ijms21186561, (13…
[cited by applicant]
Krieger, Christine C., et al., “Thyrotropin/IGF-1 Receptor Cross Talk in Graves' Ophthalmopathy Pathogenesis”, The Journal of Clinical Endocrinology & Metabolism, vol. 101, No. 6, Jun. 1, 2016, pp. 2340-2347, DOI: 10.12…
[cited by applicant]
Kumar, Seema , et al., “A Stimulatory Thyrotropin Receptor Antibody Enhances Hyaluronic Acid Synthesis in Graves' Orbital Fibroblasts: Inhibition by an IGF-I Receptor Blocking Antibody”, The Journal of Clinical Endocrin…
[cited by applicant]
Lanzolla, G. , et al., “Putative protective role of autoantibodies against the insulin-like growth factor-1 receptor in Graves' Disease: results of a pilot study”, Journal of Endocrinological Investigation, vol. 43, No.…
[cited by applicant]
Lathe, R. , “Synthetic oligonucleotide probes deduced from amino acid sequence data: Theoretical and practical considerations”, Journal of Molecular Biology, vol. 183, No. 1, May 5, 1985, pp. 1-12, DOI: 10.1016/0022-283…
[cited by applicant]
Lipsky, Peter E., “Infliximab and Methotrexate in the Treatment of Rheumatoid Arthritis”, The New England Journal of Medicine, vol. 343, No. 22, 2000, pp. 1594-1602, DOI: 10.1056/NEJM200011303432202, (9 pages).
[cited by applicant]
Liu, Alvin Y., et al., “Chimeric mouse-human IgG1 antibody that can mediate lysis of cancer cells”, Proceedings of the National Academy of Sciences, vol. 84, No. 10. May 15, 1987, pp. 3439-3443, DOI: 10.1073/pnas.84.10.…
[cited by applicant]
Liu, Alvin Y., et al., “Production of a mouse-human chimeric monoclonal antibody to CD20 with potent Fc-dependent biologic activity”, The Journal of Immunology, vol. 139, No. 10, Nov. 15, 1987, pp. 3521-3526, DOI: 10.40…
[cited by applicant]
Liu, Clarence , et al., “Randomised, double blind, placebo controlled study of interferon ß-1a in relapsing-remitting multiple sclerosis analysed by area under disability/time curves”, Journal of Neurology, Neurosurgery…
[cited by applicant]
Ludgate, Marian , “Fibrosis in dysthyroid eye disease”, EYE, vol. 34, No. 2, Dec. 16, 2019 (pp. 279-284).
[cited by applicant]
Marinó, M. , et al., “Serum antibodies against the insulin-like growth factor-1 receptor (IGF-1R) in Graves' disease and Graves' orbitopathy”, Journal of Endocrinological Investigation, vol. 42, 2019, pp. 471-480, DOI: …
[cited by applicant]
Markham, Anthony , “Teprotumumab: First Approval”, Drugs, vol. 80, No. 5, 2020, pp. 509-512, DOI: 10.1007/s40265-020-01287-y, (4 pages).
[cited by applicant]
Marks, James D., et al., “By-passing Immunization: Human Antibodies from V-gene Libraries Displayed on Phage”, Journal of Molecular Biology, vol. 222, 1991, pp. 581-597 (17 pages).
[cited by applicant]
Milgrom, Henry , et al., “Treatment of Allergic Asthma with Monoclonal Anti-IgE Antibody”, The New England Journal of Medicine, vol. 341, 1999, pp. 1966-1973, DOI: 10.1056/NEJM199912233412603, (8 pages).
[cited by applicant]
Morgan, Sarah L., et al., “Thyrotropin and Insulin-Like Growth Factor 1 Receptor Crosstalk Upregulates Sodium-lodide Symporter Expression in Primary Cultures of Human Thyrocytes”, Thyroid, vol. 26, No. 12, 2016, DOI: 10…
[cited by applicant]
Morrison, Sherie L., et al., “Chimeric human antibody molecules: Mouse antigen-binding domains with human constant region domains”, Proceedings of the National Academy of Sciences USA, Immunology, vol. 81, Nov. 1984, pp…
[cited by applicant]
Mueller, John P., et al., “Humanized porcine VCAM-specific monoclonal antibodies with chimeric lgG2/G4 constant regions block human leukocyte binding to porcine endothelial cells”, Molecular Immunology, vol. 34, No. 6, …
[cited by applicant]
Muyldermans, Serge , et al., “Recognition of antigens by single-domain antibody fragments: the superfluous luxury of paired domains”, Trends in Biochemical Sciences, vol. 26, No. 4, Apr. 1, 2001, pp. 230-235, DOI: 10.10…
[cited by applicant]
Neumann, Susanne , et al., “Targeting TSH and IGF-1 Receptors to Treat Thyroid Eye Disease”, European Thyroid Journal, vol. 9, No. 1,Nov. 2, 2020, pp. 59-65, DOI: 10.1159/000511538, (7 pages).
[cited by applicant]
Osher, Eliot , et al., “Therapeutic Targeting of the IGF Axis”, Cells, vol. 8, No. 8, 2019, 895, DOI: 10.3390/cells8080895, (25 pages).
[cited by applicant]
Ozzello, Daniel J., et al., “Early experience with teprotumumab for chronic thyroid eye disease”, American Journal of Ophthalmology Case Reports, vol. 19, 2020, 100744, DOI: 10.1016/j.ajoc.2020.100744, (3 pages).
[cited by applicant]
Patel, Amy , et al., “A New Era in the Treatment of Thyroid Eye Disease”, American Journal of Ophthalmology, vol. 208, Aug. 1, 2019 (pp. 281-288).
[cited by applicant]
Place, Robert F., et al., “Inhibiting thyrotropin/insulin-like growth factor 1 receptor crosstalk to treat Graves' ophthalmopathy: studies in orbital fibroblasts in vitro”, British Journal of Pharmacology, vol. 174, No.…
[cited by applicant]
Plückthun, A. , “Antibodies from
[cited by applicant]
Portielje, Johanna E., et al., “IL-12: a promising adjuvant for cancer vaccination”, Cancer Immunology, Immunotherapy, vol. 52, 2003, pp. 133-144, DOI: 10.1007/s00262-002-0356-5, (12 pages).
[cited by applicant]
Presta, Leonard G., “Selection, design, and engineering of therapeutic antibodies”, Journal of Allergy and Clinical Immunology, vol. 116, No. 4, Oct. 2005, pp. 731-736, DOI: 10.1016/j.jaci.2005.08.003, (6 pages).
[cited by applicant]
Pritchard, Jane , et al., “Immunoglobulin Activation of T Cell Chemoattractant Expression in Fibroblasts from Patients with Graves' Disease Is Mediated Through the Insulin-Like Growth Factor I Receptor Pathway”, The Jou…
[cited by applicant]
Riechmann, Lutz , et al., “Reshaping human antibodies for therapy”, Nature, vol. 332, 1988, pp. 323-327, DOI: 10.1038/332323a0 (5 pages).
[cited by applicant]
Riechmann, Lutz , et al., “Single domain antibodies: comparison of camel VH and camelised human VH domains”, Journal of Immunological Methods, vol. 231, No. 1-2, Dec. 10, 1999, pp. 25-38, DOI: 10.1016/S0022-1759(99)0013…
[cited by applicant]
Robbie, Gabriel J., et al., “A Novel Investigational Fe-Modified Humanized Monoclonal Antibody, Motavizumab-YTE, Has an Extended Half-Life in Healthy Adults”, Antimicrobial Agents and Chemotherapy, vol. 57, No. 12, Sep.…
[cited by applicant]
Safo, Myra B., et al., “A case of ulcerative colitis associated with teprotumumab treatment for thyroid eye disease”, American Journal of Ophthalmology Case Reports, vol. 22, Jun. 2021, 101069, DOI: 10.1016/j.ajoc.2021.…
[cited by applicant]
Salvi, M. , et al., “Medical Treatment of Graves' Orbitopathy”, Hormone and Metabolic Research, vol. 47, No. 10, 2015, pp. 779-788, DOI: 10.1055/s-0035-1554721, (10 pages).
[cited by applicant]
Salvi, Mario , “Immunotherapy for Graves' ophthalmopathy”, Current Opinion in Endocrinology & Diabetes and Obesity, vol. 21, No. 5, Oct. 2014, pp. 409-414, DOI: 10.1097/MED.0000000000000097, Abstract (1 page).
[cited by applicant]
Slamon, Dennis J., et al., “Use of Chemotherapy plus a Monoclonal Antibody against HER2 for Metastatic Breast Cancer That Overexpresses HER2”, The New England Journal of Medicine, vol. 344, No. 11, Mar. 15, 2001, pp. 78…
[cited by applicant]
Slentz, Dane H., et al., “Teprotumumab: a novel therapeutic monoclonal antibody for thyroid-associated ophthalmopathy”, Expert Opinion on Investigational Drugs, vol. 29, No. 7, pp. 645-649, DOI: 10.1080/13543784.2020.17…
[cited by applicant]
Smith, Terry J., et al., “Immunoglobulins from Patients with Graves' Disease Induce Hyaluronan Synthesis in Their Orbital Fibroblasts through the Self-Antigen, Insulin-Like Growth Factor-I Receptor”, The Journal of Clin…
[cited by applicant]
Smith, Terry J., “Teprotumumab as a Novel Therapy for Thyroid-Associated Ophthalmopathy”, Frontiers in Endocrinology, vol. 11, 2020, DOI: 10.3389/fendo.2020.610337, (10 pages).
[cited by applicant]
Smith, Terry J., et al., “Teprotumumab for Thyroid-Associated Ophthalmopathy”, The New England Journal of Medicine, vol. 376, N. 18, 2017, pp. 1748-1761, DOI: 10.1056/NEJMoa1614949, (14 pages).
[cited by applicant]
Storz, Ulrich , “Intellectual property protection”, mAbs, vol. 3, No. 3, 2011, pp. 310-317, DOI: 10.4161/mabs.3.3.15530, (9 pages).
[cited by applicant]
Taylor, Peter N., et al., “New insights into the pathogenesis and nonsurgical management of Graves orbitopathy”, Nature Reviews Endocrinology, vol. 16, No. 2, 2020, pp. 104-116, DOI: 10.1038/s41574-019-0305-4, (13 pages…
[cited by applicant]
Tsui, Shanli , et al., “Evidence for an Association between Thyroid-Stimulating Hormone and Insulin-Like Growth Factor 1 Receptors: A Tale of Two Antigens Implicated in Graves' Disease”, The Journal of Immunology, vol. …
[cited by applicant]
Tsurushita, Naoya , et al., “Humanization of a chicken anti-IL-12 monoclonal antibody”, Journal of Immunological Methods, vol. 295, No. 1-2, Dec. 2004, pp. 9-19, DOI: 10.1016/j.jim.2004.08.018, (11 pages).
[cited by applicant]
Ugradar, Shoaib , et al., “A Paradigm Shift in the Management of Thyroid Eye Disease How Teprotumumab Has Changed the Therapeutic Interface.”, Journal of neuro-ophthalmology: the official journal of the North American N…
[cited by applicant]
Ugradar, Shoaib , et al., “Improvement of asymmetric thyroid eye disease with teprotumumab”, British Journal of Ophthalmology, 2021, DOI: 10.1136/bjophthalmol-2020-318314, (5 pages).
[cited by applicant]
Ugradar, Shoaib , et al., “Teprotumumab for non-inflammatory thyroid eye disease (TED): evidence for increased IGF-1R expression”, Eye, vol. 35, No. 9, 2021, pp. 2607-2612, DOI: 10.1038/s41433-020-01297-w, (6 pages).
[cited by applicant]
Ugradar, Shoaib , et al., “Teprotumumab for the treatment of chronic thyroid eye disease”, Eye (London, England), vol. 36, No. 8, Aug. 2022, pp. 1553-1559, DOI:10.1038/s41433-021-01593-z (7 pages).
[cited by applicant]
Weightman, David R., et al., “Autoantibodies to Igf-1 Binding Sites in Thyroid Associated Ophthalmopathy”, Autoimmunity, vol. 16, No. 4, 1993, pp. 251-257, DOI: 10.3109/08916939309014643, (7 pages).
[cited by applicant]
Xin, Yan , et al., “Pharmacokinetics and Exposure-Response Relationship of Teprotumumab, an Insulin-Like Growth Factor-1 Receptor-Blocking Antibody, in Thyroid Eye Disease”, Clinical Pharmacokinetics, vol. 60, 2021, pp.…
[cited by applicant]
Yang, James C., et al., “A Randomized Trial of Bevacizumab, an Anti-Vascular Endothelial Growth Factor Antibody, for Metastatic Renal Cancer”, The New England Journal of Medicine, vol. 349, No. 5, Jul. 31, 2003, pp. 427…
[cited by applicant]
Yu, Run , “Thyroid function suppression after initiation of teprotumumab treatment”, Endocrine, vol. 73, No. 3, 2021, pp. 561-562, DOI: 10.1007/s12020-021-02676-3, (2 pages).
[cited by applicant]
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