( 12 ) United States Patent
`Yancopoulos
`
`( 10 ) Patent No .: US 10,888,601 B2
`( 45 ) Date of Patent :
`* Jan . 12 , 2021
`
`US010888601B2
`
`( 54 ) USE OF A VEGF ANTAGONIST TO TREAT
`ANGIOGENIC EYE DISORDERS
`( 71 ) Applicant : REGENERON
`PHARMACEUTICALS , INC . ,
`Tarrytown , NY ( US )
`( 72 ) Inventor : George D. Yancopoulos , Yorktown
`Heights , NY ( US )
`( 73 ) Assignee : REGENERON
`PHARMACEUTICALS , INC . ,
`Tarrytown , NY ( US )
`Subject to any disclaimer , the term of this
`patent is extended or adjusted under 35
`U.S.C. 154 ( b ) by 0 days .
`This patent is subject to a terminal dis
`claimer .
`( 21 ) Appl . No .: 16 / 397,267
`( 22 ) Filed :
`Apr. 29 , 2019
`( 65 )
`Prior Publication Data
`Aug. 15 , 2019
`US 2019/0247463 A1
`
`( * ) Notice :
`
`( 63 )
`
`Related U.S. Application Data
`Continuation of application No. 16 / 159,282 , filed on
`Oct. 12 , 2018 , which is a continuation of application
`No. 15 / 471,506 , filed on Mar. 28 , 2017 , now Pat . No.
`10,130,691 , which is a continuation of application
`No. 14 / 972,560 , filed on Dec. 17 , 2015 , now Pat . No.
`9,669,069 , which is a continuation of application No.
`13 / 940,370 , filed on Jul . 12 , 2013 , now Pat . No.
`9,254,338 , which is a continuation - in - part of
`application No. PCT / US2012 / 020855 , filed on Jan.
`11 , 2012 .
`( 60 ) Provisional application No. 61 / 432,245 , filed on Jan.
`13 , 2011 , provisional application No. 61 / 434,836 ,
`filed on Jan. 21 , 2011 , provisional application No.
`61 / 561,957 , filed on Nov. 21 , 2011 .
`Int . Cl .
`( 2006.01 )
`A61K 38/17
`CO7K 14/71
`( 2006.01 )
`( 2006.01 )
`COZK 19/00
`COOK 16/22
`( 2006.01 )
`A61K 9/00
`( 2006.01 )
`( 2006.01 )
`A61K 39/00
`U.S. Cl .
`A61K 38/179 ( 2013.01 ) ; A61K 9/0048
`CPC
`( 2013.01 ) ; C07K 14/71 ( 2013.01 ) ; CO7K 16/22
`( 2013.01 ) ; A61K 2039/505 ( 2013.01 ) ; CO7K
`2319/30 ( 2013.01 ) ; CO7K 2319/32 ( 2013.01 )
`Field of Classification Search
`None
`See application file for complete search history .
`References Cited
`U.S. PATENT DOCUMENTS
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`7,070,959 B1
`12/2007 Wiegand
`7,303,746 B2
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`6/2017 Yancopoulos
`11/2018 Yancopoulos
`9/2019 Dix et al .
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`11/2005 Wiegand et al .
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`1/2020 Furfine et al .
`
`FOREIGN PATENT DOCUMENTS
`
`JP
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`
`2010-509369
`WO 2000/75319
`WO 2004/106378 A2
`WO 2005/000895 A2
`WO 2006/047325
`WO 2007/022101 A2
`WO 2008/063932
`WO 2012/097019
`
`3/2010
`12/2000
`12/2004
`1/2005
`3/2006
`2/2007
`5/2008
`7/2012
`
`OTHER PUBLICATIONS
`Updated Information from ClinicalTrials.gov archive History of
`Changes for Study : NCT01012973 Vascular Endothelial Growth
`Factor ( VEGF ) Trap - Eye : Investigation of Efficacy and Safety in
`Central Retinal Vein Occlusion ( CRVO ) ( GALILEO ) 38 pages ,
`Latest version submitted Oct. 27 , 2014 on Clinical Trials.gov
`( NCT01012973_01182013_27424.1 ) .
`Updated Information from Clinical Trials.gov archive History of
`Changes for Study : NCT01012973 Vascular Endothelial Growth
`Factor ( VEGF ) Trap - Eye : Investigation of Efficacy and Safety in
`Central Retinal Vein Occlusion ( CRVO ) ( GALILEO ) 10 pages ,
`Latest version submitted Oct. 27 , 2014 on Clinical Trials.gov
`( NCT01012973_01252011_27433.1 ) .
`( Continued )
`
`Primary Examiner Christine J Saoud
`Assistant Examiner Jon M Lockard
`( 74 ) Attorney , Agent , or Firm - Thomas Triolo ; Karl
`Bozicevic
`
`( 57 )
`ABSTRACT
`The present invention provides methods for treating angio
`genic eye disorders by sequentially administering multiple
`doses of a VEGF antagonist to a patient . The methods of the
`present invention include the administration of multiple
`doses of a VEGF antagonist to a patient at a frequency of
`once every 8 or more weeks . The methods of the present
`invention are useful for the treatment of angiogenic eye
`disorders such as age related macular degeneration , diabetic
`retinopathy , diabetic macular edema , central retinal vein
`occlusion , branch retinal vein occlusion , and corneal neo
`vascularization .
`
`47 Claims , 1 Drawing Sheet
`Specification includes a Sequence Listing .
`
`Mylan Exhibit 1001
`Mylan v. Regeneron, IPR2022-01226
`Page 1
`
`

`

`US 10,888,601 B2
`Page 2
`
`( 56 )
`
`References Cited
`
`OTHER PUBLICATIONS
`Updated Information from ClinicalTrials.gov archive History of
`Changes for Study : NCT01012973 Vascular Endothelial Growth
`Factor ( VEGF ) Trap - Eye : Investigation of Efficacy and Safety in
`Central Retinal Vein Occlusion ( CRVO ) ( GALILEO ) 11 pages ,
`Latest version submitted Oct. 27 , 2014 on Clinical Trials.gov
`( NCT01012973_01262012_27428.1 ) .
`Updated Information from ClinicalTrials.gov archive History of
`Changes for Study : NCT01012973 Vascular Endothelial Growth
`Factor ( VEGF ) Trap - Eye : Investigation of Efficacy and Safety in
`Central Retinal Vein Occlusion ( CRVO ) ( GALILEO ) 38 pages ,
`Latest version submitted Oct. 27 , 2014 on Clinical Trials.gov
`( NCT01012973_01302013_27423.1 ) .
`Updated Information from ClinicalTrials.gov archive History of
`Changes for Study : NCT01012973 Vascular Endothelial Growth
`Factor ( VEGF ) Trap - Eye : Investigation of Efficacy and Safety in
`Central Retinal Vein Occlusion ( CRVO ) ( GALILEO ) 12 pages ,
`Latest version submitted Oct. 27 , 2014 on Clinical Trials.gov
`( NCT01012973_02092010_27442.1 ) .
`Updated Information from ClinicalTrials.gov archive History of
`Changes for Study : NCT01012973 Vascular Endothelial Growth
`Factor ( VEGF ) Trap - Eye : Investigation of Efficacy and Safety in
`Central Retinal Vein Occlusion ( CRVO ) ( GALILEO ) 11 pages ,
`Latest version submitted Oct. 27 , 2014 on Clinical Trials.gov
`( NCT01012973_02202012_27427.1 ) .
`Updated Information from ClinicalTrials.gov archive History of
`Changes for Study : NCT01012973 Vascular Endothelial Growth
`Factor ( VEGF ) Trap - Eye : Investigation of Efficacy and Safety in
`Central Retinal Vein Occlusion ( CRVO ) ( GALILEO ) 12 pages ,
`Latest version submitted Oct. 27 , 2014 on ClinicalTrials.gov
`( NCT01012973_03162010_27441.1 ) .
`Updated Information from ClinicalTrials.gov archive History of
`Changes for Study : NCT01012973 Vascular Endothelial Growth
`Factor ( VEGF ) Trap - Eye : Investigation of Efficacy and Safety in
`Central Retinal Vein Occlusion ( CRVO ) ( GALILEO ) 10 pages ,
`Latest version submitted Oct. 27 , 2014 on Clinical Trials.gov
`( NCT01012973_04082011_27432.1 ) .
`Updated Information from ClinicalTrials.gov archive History of
`Changes for Study : NCT01012973 Vascular Endothelial Growth
`Factor ( VEGF ) Trap - Eye : Investigation of Efficacy and Safety in
`Central Retinal Vein Occlusion ( CRVO ) ( GALILEO ) 12 pages ,
`Latest version submitted Oct. 27 , 2014 on Clinical Trials.gov
`( NCT01012973_04162010_27440.1 ) .
`Updated Information from ClinicalTrials.gov archive History of
`Changes for Study : NCT01012973 Vascular Endothelial Growth
`Factor ( VEGF ) Trap - Eye : Investigation of Efficacy and Safety in
`Central Retinal Vein Occlusion ( CRVO ) ( GALILEO ) 10 pages ,
`Latest version submitted Oct. 27 , 2014 on Clinical Trials.gov
`( NCT01012973_06232011_27431.1 ) .
`Updated Information from ClinicalTrials.gov archive History of
`Changes for Study : NCT01012973 Vascular Endothelial Growth
`Factor ( VEGF ) Trap - Eye : Investigation of Efficacy and Safety in
`Central Retinal Vein Occlusion ( CRVO ) ( GALILEO ) 12 pages ,
`Latest version submitted Oct. 27 , 2014 on Clinical Trials.gov
`( NCT01012973_07222010_27439.1 ) .
`Updated Information from ClinicalTrials.gov archive History of
`Changes for Study : NCT01012973 Vascular Endothelial Growth
`Factor ( VEGF ) Trap - Eye : Investigation of Efficacy and Safety in
`Central Retinal Vein Occlusion ( CRVO ) ( GALILEO ) 12 pages ,
`Latest version submitted Oct. 27 , 2014 on Clinical Trials.gov
`( NCT01012973_08252010_27438.1 ) .
`Updated Information from ClinicalTrials.gov archive History of
`Changes for Study : NCT01012973 Vascular Endothelial Growth
`Factor ( VEGF ) Trap - Eye : Investigation of Efficacy and Safety in
`Central Retinal Vein Occlusion ( CRVO ) ( GALILEO ) 10 pages ,
`Latest version submitted Oct. 27 , 2014 on Clinical Trials.gov
`( NCT01012973_08262010_27437.1 ) .
`
`Updated Information from Clinical Trials.gov archive History of
`Changes for Study : NCT01012973 Vascular Endothelial Growth
`Factor ( VEGF ) Trap - Eye : Investigation of Efficacy and Safety in
`Central Retinal Vein Occlusion ( CRVO ) ( GALILEO ) 10 pages ,
`Latest version submitted Oct. 27 , 2014 on Clinical Trials.gov
`( NCT01012973_09082010_27436.1 ) .
`Updated Information from ClinicalTrials.gov archive History of
`Changes for Study : NCT01012973 Vascular Endothelial Growth
`Factor ( VEGF ) Trap - Eye : Investigation of Efficacy and Safety in
`Central Retinal Vein Occlusion ( CRVO ) ( GALILEO ) 10 pages ,
`Latest version submitted Oct. 27 , 2014 on ClinicalTrials.gov
`( NCT01012973_09192011_27430.1 ) .
`Updated Information from ClinicalTrials.gov archive History of
`Changes for Study : NCT01012973 Vascular Endothelial Growth
`Factor ( VEGF ) Trap - Eye : Investigation of Efficacy and Safety in
`Central Retinal Vein Occlusion ( CRVO ) ( GALILEO ) 10 pages ,
`Latest version submitted Oct. 27 , 2014 on Clinical Trials.gov
`( NCT01012973_10042010_27435.1 ) .
`Updated Information from Clinical Trials.gov archive History of
`Changes for Study : NCT01012973 Vascular Endothelial Growth
`Factor ( VEGF ) Trap - Eye : Investigation of Efficacy and Safety in
`Central Retinal Vein Occlusion ( CRVO ) ( GALILEO ) 38 pages ,
`Latest version submitted Oct. 27 , 2014 on Clinical Trials.gov
`( NCT01012973_10232012_27426.1 ) .
`Updated Information from ClinicalTrials.gov archive History of
`Changes for Study : NCT01012973 Vascular Endothelial Growth
`Factor ( VEGF ) Trap - Eye : Investigation of Efficacy and Safety in
`Central Retinal Vein Occlusion ( CRVO ) ( GALILEO ) 38 pages ,
`Latest version submitted Oct. 27 , 2014 on Clinical Trials.gov
`( NCT01012973_10272013_27422.1 ) .
`Updated Information from ClinicalTrials.gov archive History of
`Changes for Study : NCT01012973 Vascular Endothelial Growth
`Factor ( VEGF ) Trap - Eye : Investigation of Efficacy and Safety in
`Central Retinal Vein Occlusion ( CRVO ) ( GALILEO ) 10 pages ,
`Latest version submitted Oct. 27 , 2014 on Clinical Trials.gov
`( NCT01012973_11012010_27434.1 ) .
`Updated Information from ClinicalTrials.gov archive History of
`Changes for Study : NCT01012973 Vascular Endothelial Growth
`Factor ( VEGF ) Trap - Eye : Investigation of Efficacy and Safety in
`Central Retinal Vein Occlusion ( CRVO ) ( GALILEO ) 12 pages ,
`Latest version submitted Oct. 27 , 2014 on Clinical Trials.gov
`( NCT01012973_11132009_27444.1 ) .
`Updated Information from ClinicalTrials.gov archive History of
`Changes for Study : NCT01012973 Vascular Endothelial Growth
`Factor ( VEGF ) Trap - Eye : Investigation of Efficacy and Safety in
`Central Retinal Vein Occlusion ( CRVO ) ( GALILEO ) 10 pages ,
`Latest version submitted Oct. 27 , 2014 on Clinical Trials.gov
`( NCT01012973_11292011_27429.1 ) .
`Updated Information from Clinical Trials.gov archive History of
`Changes for Study : NCT01012973 Vascular Endothelial Growth
`Factor ( VEGF ) Trap - Eye : Investigation of Efficacy and Safety in
`Central Retinal Vein Occlusion ( CRVO ) ( GALILEO ) 38 pages ,
`Latest version submitted Oct. 27 , 2014 on Clinical Trials.gov
`( NCT01012973_12182012_27425.1 ) .
`Updated Information from Clinical Trials.gov archive History of
`Changes for Study : NCT01012973 Vascular Endothelial Growth
`Factor ( VEGF ) Trap - Eye : Investigation of Efficacy and Safety in
`Central Retinal Vein Occlusion ( CRVO ) ( GALILEO ) 12 pages ,
`Latest version submitted Oct. 27 , 2014 on Clinical Trials.gov
`( NCT01012973_12212010_27443.1 ) .
`U.S. Appl . No. 16 / 055,847 — Third Party Submissions dated May 1 ,
`2019 .
`U.S. Appl . No. 16 / 159,282 — Third Party Submissions dated May
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`
`Mylan Exhibit 1001
`Mylan v. Regeneron, IPR2022-01226
`Page 2
`
`

`

`US 10,888,601 B2
`Page 3
`
`( 56 )
`
`References Cited
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`results first posted Nov. 22 , 2012 ; last update posted Nov. 3 , 2014 ;
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`
`Mylan Exhibit 1001
`Mylan v. Regeneron, IPR2022-01226
`Page 3
`
`

`

`US 10,888,601 B2
`Page 4
`
`( 56 )
`
`References Cited
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`
`Mylan Exhibit 1001
`Mylan v. Regeneron, IPR2022-01226
`Page 4
`
`

`

`US 10,888,601 B2
`Page 5
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