IP Library › Granted Patent US 12,685,771
Granted Patent B2
US 12,685,771 · App. 17/215,604 · Granted Jul 21, 2026

Methods for treating or preventing asthma by administering an IL-4R antagonist

Inventors: Gianluca Pirozzi (Berkeley Heights, NJ); Franck Skobieranda (Flourtown, PA); Yongtao Li (Springfield, NJ); Neil Graham (Croton-on-Hudson, NY); Steven P. Weinstein (Hartsdale, NY)
Assignees: SANOFI BIOTECHNOLOGY; REGENERON PHARMACEUTICALS, INC.
A61K39/3955A61K31/00A61K31/137A61K31/167A61K31/56A61K31/569A61K31/58C07K16/2866A61K2039/54A61K2039/545C07K2317/21
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 12,685,771
App. No.
17/215,604
Filed
Mar 29, 2021
Granted
Jul 21, 2026
Kind
B2
Art Unit
1643
USPC
424/144.1
Abstract

The invention provides methods for treating or preventing asthma and associated conditions in a patient. The methods featured in the invention comprise administering to a subject in need thereof a therapeutic composition comprising an interleukin-4 receptor (IL-4R) antagonist, such as an anti-IL-4R antibody.

Claims (74)

1 . A method for add-on maintenance treatment of moderate to severe asthma in a subject in need thereof comprising administering to the subject an initial dose of 600 mg of an antibody that specifically binds to interleukin-4 receptor (IL-4R) comprising three heavy chain complementarity determining region (HCDR) sequences comprising SEQ ID NOs: 3, 4 and 5, and three light chain complementarity determining region (LCDR) sequences comprising SEQ ID NOs: 6, 7 and 8, and

one or more secondary doses of 300 mg of the antibody.

2 . The method of claim 1 , wherein the antibody that specifically binds to IL-4R comprises a heavy chain variable region (HCVR) comprising the amino acid sequence of SEQ ID NO: 1 and a light chain variable region (LCVR) comprising the amino acid sequence of SEQ ID NO: 2.

3 . The method of claim 2 , wherein the antibody is dupilumab.

4 . The method of claim 3 , wherein the one or more secondary doses are administered every other week (q2w).

5 . The method of claim 4 , wherein the one or more secondary doses are administered for at least 24 weeks.

6 . The method of claim 5 , wherein the dupilumab is administered to the subject subcutaneously.

7 . The method of claim 6 , wherein the subject has a blood eosinophil count of greater than or equal to 300 cells/μL.

8 . The method of claim 6 , wherein one or both of inhaled corticosteroid (ICS) and long-acting beta-agonist (LABA) are administered for the duration of administration of the dupilumab, wherein the ICS is selected from the group consisting of mometasone furoate, budesonide, and fluticasone propionate, and wherein the LABA is selected from the group consisting of formoterol and salmeterol.

9 . A method for increasing forced expiratory volume in 1 second (FEV1) in liters to treat moderate to severe asthma in a subject in need thereof comprising administering to the subject a combination therapy comprising:

i) one or more maintenance doses of an ICS,

ii) one or more maintenance doses of a LABA,

iii) an initial dose of 600 mg of an antibody that specifically binds to IL-4R comprising three HCDR sequences comprising SEQ ID NOs: 3, 4 and 5, and three LCDR sequences comprising SEQ ID NOs: 6, 7 and 8, and

iv) one or more secondary doses of 300 mg of the antibody,

wherein the ICS and LABA are administered for the duration of administration of the antibody.

10 . A method for improving one or more moderate to severe asthma-associated parameter(s) in a subject in need thereof comprising administering to the subject a combination therapy comprising:

i.) One or more maintenance doses of an ICS,

ii) one or more maintenance doses of a LABA,

iii) an initial dose of 600 mg of an antibody that specifically binds to IL-4R comprising three HCDR sequences comprising SEQ ID NOs: 3, 4 and 5, and three light chain complementarity determining region (LCDR) sequences comprising SEQ ID NOs: 6, 7 and 8, and

iv) one or more secondary doses of 300 mg of the antibody,

wherein the ICS and LABA are administered for the duration of administration of the antibody.

11 . A method for reducing an asthma patient's dependence on one or both of ICS and LABA for the treatment of one or more moderate to severe asthma exacerbations comprising:

(a) selecting a patient who has moderate-to-severe asthma that is uncontrolled with a background asthma therapy comprising an ICS, a LABA, or a combination thereof; and

(b) administering to the patient a combination therapy comprising:

i) one or more maintenance doses of an ICS,

ii) one or more maintenance doses of a LABA,

iii) an initial dose of 600 mg of an antibody that specifically binds to IL-4R comprising three HCDR sequences comprising SEQ ID NOs: 3, 4 and 5, and three LCDR sequences comprising SEQ ID NOs: 6, 7 and 8, and

iv) one or more secondary doses of 300 mg of the antibody, wherein the ICS and LABA are administered for the duration of administration of the antibody.

12 . The method of claim 8 , wherein the subject is 12 years of age and above.

13 . A method for add-on maintenance treatment of moderate to severe asthma in a subject in need thereof comprising administering to the subject

an initial dose of 400 mg of an antibody or that specifically binds to IL-4R comprising three HCDR sequences comprising SEQ ID NOs: 3, 4, and 5, and three LCDR sequences comprising SEQ ID NOs: 6, 7, and 8, and

one or more secondary doses of 200 mg of the antibody.

14 . The method of claim 13 , wherein the antibody that specifically binds to IL-4R comprises an HCVR comprising the amino acid sequence of SEQ ID NO: 1 and an LCVR comprising the amino acid sequence of SEQ ID NO: 2.

15 . The method of claim 14 , wherein the antibody is dupilumab.

16 . The method of claim 15 , wherein the one or more secondary doses are administered every other week (q2w).

17 . The method of claim 16 , wherein the secondary doses are administered for at least 24 weeks.

18 . The method of claim 3 , wherein the dupilumab is administered to the subject subcutaneously.

19 . The method of claim 18 , wherein the subject has a blood eosinophil count of greater than or equal to 300 cells/μL.

20 . The method of claim 18 , wherein one or both of ICS and LABA are administered for the duration of administration of the dupilumab, wherein the ICS is selected from the group consisting of mometasone furoate, budesonide, and fluticasone propionate, and wherein the LABA is selected from the group consisting of formoterol and salmeterol.

21 . The method of claim 20 , wherein the subject is 12 years of age and above.

22 . A method for increasing FEV1 in liters to treat moderate to severe asthma in a subject in need thereof comprising administering to the subject a combination therapy comprising:

i) one or more maintenance doses of an ICS,

ii) one or more maintenance doses of a LABA,

iii) an initial dose of 400 mg of an antibody that specifically binds to IL-4R comprising three HCDR sequences comprising SEQ ID NOs: 3, 4, and 5, and three LCDR sequences comprising SEQ ID NOs: 6, 7, and 8, and

iv) one or more secondary doses of 200 mg of the antibody,

wherein the ICS and LABA are administered for the duration of administration of the antibody.

23 . A method for improving one or more moderate to severe asthma-associated parameter(s) in a subject in need thereof comprising administering to the subject a combination therapy comprising:

i) one or more maintenance doses of an ICS,

ii) one or more maintenance doses of a LABA,

iii) an initial dose of 400 mg of an antibody that specifically binds to IL-4R comprising three HCDR sequences comprising SEQ ID NOs: 3, 4, and 5, and three LCDR sequences comprising SEQ ID NOs: 6, 7, and 8, and

iv) one or more secondary doses of 200 mg of the antibody,

wherein the ICS and LABA are administered for the duration of administration of the antibody.

24 . A method for reducing an asthma patient's dependence on one or both of ICS and LABA for the treatment of one or more exacerbations of moderate to severe asthma comprising:

(a) selecting a patient who has moderate to severe asthma that is uncontrolled with a background asthma therapy comprising an ICS, a LABA, or a combination thereof; and

(b) administering to the patient a combination therapy comprising:

i) one or more maintenance doses of an ICS,

ii) one or more maintenance doses of a LABA,

iii) an initial dose of 400 mg of an antibody that specifically binds to IL-4R comprising three HCDR sequences comprising SEQ ID NOs: 3, 4, and 5, and three LCDR sequences comprising SEQ ID NOs: 6, 7, and 8, and

iv) one or more secondary doses of 200 mg of the antibody,

wherein the ICS and LABA are administered for the duration of administration of the antibody.

25 . A method for add-on maintenance treatment of moderate to severe asthma in a subject in need thereof, comprising administering to the subject by subcutaneous injection an initial dose of 600 mg of dupilumab, and one or more secondary doses of 300 mg of dupilumab administered every other week (q2w), wherein the subject is 12 years of age and above, and wherein the subject has an eosinophilic phenotype.

26 . A method for add-on maintenance treatment of moderate to severe asthma in a subject in need thereof, comprising administering to the subject by subcutaneous injection an initial dose of 400 mg of dupilumab, and one or more secondary doses of 200 mg of dupilumab administered every other week (q2w), wherein the subject is 12 years of age and above, and wherein the subject has an eosinophilic phenotype.

27 . The method of claim 6 , where the dupilumab is administered subcutaneously using an autoinjector, a needle and syringe, or a pen delivery device.

28 . The method of claim 18 , where the dupilumab is administered subcutaneously using an autoinjector, a needle and syringe, or a pen delivery device.

29 . The method of claim 6 , wherein the subject has a blood eosinophil count of 200 to 299 cells/μL.

30 . The method of claim 3 , wherein the subject has a blood eosinophil count of less than 200 cells/μL.

31 . The method of claim 18 , wherein the subject has a blood eosinophil count of 200 to 299 cells/μL.

32 . The method of claim 18 , wherein the subject has a blood eosinophil count of less than 200 cells/μL.

33 . The method of claim 25 , wherein the subject has a blood eosinophil count of greater than or equal to 300 cells/μL.

34 . The method of claim 26 , wherein the subject has a blood eosinophil count of greater than or equal to 300 cells/μL.

35 . The method of claim 33 , wherein the subject has moderate persistent asthma.

36 . The method of claim 33 , wherein the subject has severe persistent asthma.

37 . The method of claim 34 , wherein the subject has moderate persistent asthma.

38 . The method of claim 34 , wherein the subject has severe persistent asthma.

Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 16, 2024
From: LI, YONGTAO; PIROZZI, GIANLUCA; SKOBIERANDA, FRANCK
To: SANOFI
Reel/Frame 068316/0964 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 16, 2024
From: GRAHAM, NEIL; WEINSTEIN, STEVEN P.
To: REGENERON PHARMACEUTICALS, INC.
Reel/Frame 068317/0143 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 16, 2024
From: SANOFI
To: SANOFI BIOTECHNOLOGY
Reel/Frame 068317/0494 →
Priority Claims (1)
EP 14306413 · Sep 15, 2014 · regional
Continuity (5)
Continuation 16157708 · Oct 11, 2018
Continuation 14627728 · Feb 20, 2015
Provisional Application 62077669 · Nov 10, 2014
Provisional Application 61943019 · Feb 21, 2014
Related Publication 20210322546A1 · Oct 21, 2021
References Cited (400)
US 5599905A · Mosley et al. · 1997 [cited by applicant]
US 5714146A · Lewis et al. · 1998 [cited by applicant]
US 5717072A · Mosley et al. · 1998 [cited by applicant]
US 5856296A · Mosley et al. · 1999 [cited by applicant]
US 5985280A · Ritter et al. · 1999 [cited by applicant]
US 6156877A · Ritter et al. · 2000 [cited by applicant]
US 6391581B1 · Mosley et al. · 2002 [cited by applicant]
US 6548655B1 · Mosley et al. · 2003 [cited by applicant]
US 6596541B2 · Murphy et al. · 2003 [cited by applicant]
US 6716587B2 · Mosley et al. · 2004 [cited by applicant]
US 6927044B2 · Stahl et al. · 2005 [cited by applicant]
US 7141653B2 · Greenfeder et al. · 2006 [cited by applicant]
US 7186809B2 · Pluenneke · 2007 [cited by applicant]
US 7317090B2 · Mosley et al. · 2008 [cited by applicant]
US 7422742B2 · Greenfeder et al. · 2008 [cited by applicant]
US 7465450B2 · Pluenneke · 2008 [cited by applicant]
US 7531169B2 · Singh et al. · 2009 [cited by applicant]
US 7582298B2 · Stevens et al. · 2009 [cited by applicant]
US 7605237B2 · Stevens et al. · 2009 [cited by applicant]
US 7608693B2 · Martin et al. · 2009 [cited by applicant]
US 7794717B2 · Stevens et al. · 2010 [cited by applicant]
US 8030003B2 · Rothenberg · 2011 [cited by applicant]
US 8075887B2 · Martin et al. · 2011 [cited by applicant]
US 8075897B2 · Spertini et al. · 2011 [cited by applicant]
US 8092802B2 · Stevens et al. · 2012 [cited by applicant]
US 8092804B2 · Eriksson et al. · 2012 [cited by applicant]
US 8178098B2 · Lahn et al. · 2012 [cited by applicant]
US 8252284B2 · Singh et al. · 2012 [cited by applicant]
US 8324192B2 · Dohil et al. · 2012 [cited by applicant]
US 8337839B2 · Martin et al. · 2012 [cited by applicant]
US 8338135B2 · Stevens et al. · 2012 [cited by applicant]
US 8497528B2 · Lee et al. · 2013 [cited by applicant]
US 8604171B2 · Singh et al. · 2013 [cited by applicant]
US 8637239B2 · Furuta et al. · 2014 [cited by applicant]
US 8735095B2 · Martin et al. · 2014 [cited by applicant]
US 8945559B2 · Dix et al. · 2015 [cited by applicant]
US 9238692B2 · Dix et al. · 2016 [cited by applicant]
US 9415015B2 · Jacobi et al. · 2016 [cited by applicant]
US 9574004B2 · Ardeleanu · 2017 [cited by examiner]
US 9864091B2 · Chen et al. · 2018 [cited by applicant]
US 10059771B2 · Mannent et al. · 2018 [cited by applicant]
US 10066017B2 · Mannent et al. · 2018 [cited by applicant]
US 10137193B2 · Pirozzi · 2018 [cited by examiner]
US 10392439B2 · Stahl et al. · 2019 [cited by applicant]
US 10485844B2 · Radin · 2019 [cited by applicant]
US 10676530B2 · Stahl et al. · 2020 [cited by applicant]
US 10815205B2 · Collin-Kropelin et al. · 2020 [cited by applicant]
US 11034768B2 · Amin · 2021 [cited by examiner]
US 11167004B2 · Radin et al. · 2021 [cited by applicant]
US 11214621B2 · Mannent et al. · 2022 [cited by applicant]
US 11292847B2 · Bansal et al. · 2022 [cited by applicant]
US 11485788B2 · Stahl et al. · 2022 [cited by applicant]
US 11771743B2 · Hamilton et al. · 2023 [cited by applicant]
US 11845800B2 · Ardeleanu et al. · 2023 [cited by applicant]
US 11866503B2 · Orengo et al. · 2024 [cited by applicant]
US 11964016B2 · Asrat et al. · 2024 [cited by applicant]
US 12090201B2 · Bansal et al. · 2024 [cited by applicant]
US 12398212B2 · Staudinger et al. · 2025 [cited by applicant]
US 20020002132A1 · Pluenneke · 2002 [cited by applicant]
US 20030103938A1 · Jinquan et al. · 2003 [cited by applicant]
US 20030113387A1 · Tsuchida et al. · 2003 [cited by applicant]
US 20030124121A1 · Pluenneke · 2003 [cited by applicant]
US 20050031609A1 · Hultsch et al. · 2005 [cited by applicant]
US 20050032164A1 · Watson et al. · 2005 [cited by applicant]
US 20050074462A1 · Holmgren et al. · 2005 [cited by applicant]
US 20050118176A1 · Mosley et al. · 2005 [cited by applicant]
US 20050255532A1 · Ruben et al. · 2005 [cited by applicant]
US 20050282181A1 · Yan et al. · 2005 [cited by applicant]
US 20060013811A1 · Dina · 2006 [cited by applicant]
US 20070041976A1 · Pluenneke et al. · 2007 [cited by applicant]
US 20070274996A1 · Carter et al. · 2007 [cited by applicant]
US 20080054606A1 · Mitsuo et al. · 2008 [cited by applicant]
US 20080160035A1 · Stevens et al. · 2008 [cited by applicant]
US 20090062168A1 · Timar et al. · 2009 [cited by applicant]
US 20090074793A1 · Martin et al. · 2009 [cited by applicant]
US 20090098142A1 · Kassalan et al. · 2009 [cited by applicant]
US 20090264392A1 · Warndahl et al. · 2009 [cited by applicant]
US 20100021476A1 · Stevens et al. · 2010 [cited by applicant]
US 20100047254A1 · Martin et al. · 2010 [cited by applicant]
US 20100144646A1 · Paterson · 2010 [cited by applicant]
US 20100291107A1 · Stevens et al. · 2010 [cited by applicant]
US 20110195500A1 · Rothenberg · 2011 [cited by applicant]
US 20120004205A1 · Rothenberg · 2012 [cited by applicant]
US 20120047954A1 · Coppola et al. · 2012 [cited by applicant]
US 20120052072A1 · Martin et al. · 2012 [cited by applicant]
US 20120088814A1 · Gregory · 2012 [cited by applicant]
US 20120097565A1 · Dix et al. · 2012 [cited by applicant]
US 20120135010A1 · Stevens et al. · 2012 [cited by applicant]
US 20120164080A1 · Hill et al. · 2012 [cited by applicant]
US 20120207815A1 · Benhamou et al. · 2012 [cited by applicant]
US 20120240930A1 · Kristensson et al. · 2012 [cited by applicant]
US 20130052190A1 · Collins et al. · 2013 [cited by applicant]
US 20130078675A1 · Martin et al. · 2013 [cited by applicant]
US 20130324435A1 · Rothenberg et al. · 2013 [cited by applicant]
US 20140056920A1 · Ardeleanu et al. · 2014 [cited by applicant]
US 20140072583A1 · Ardeleanu et al. · 2014 [cited by applicant]
US 20140187523A1 · Dohil et al. · 2014 [cited by applicant]
US 20140271658A1 · Murphy et al. · 2014 [cited by applicant]
US 20140271681A1 · Martin et al. · 2014 [cited by applicant]
US 20140356372A1 · Stahl et al. · 2014 [cited by applicant]
US 20150017182A1 · Mannent et al. · 2015 [cited by applicant]
US 20150185228A1 · Reisacher · 2015 [cited by applicant]
US 20150246119A1 · Pirozzi et al. · 2015 [cited by applicant]
US 20160102147A1 · Dix et al. · 2016 [cited by applicant]
US 20160152718A1 · Kostic et al. · 2016 [cited by applicant]
US 20160185866A1 · Mannent et al. · 2016 [cited by applicant]
US 20180016343A1 · Ardeleanu et al. · 2018 [cited by applicant]
US 20180155436A1 · Orengo et al. · 2018 [cited by applicant]
US 20190040146A1 · Mannent et al. · 2019 [cited by applicant]
US 20190040147A1 · Mannent et al. · 2019 [cited by applicant]
US 20190078160A1 · Dressen et al. · 2019 [cited by applicant]
US 20190125865A1 · Pirozzi et al. · 2019 [cited by applicant]
US 20190169299A1 · Amin · 2019 [cited by applicant]
US 20190364622A1 · Carlsson et al. · 2019 [cited by applicant]
US 20190367622A1 · Graham · 2019 [cited by applicant]
US 20210000949A1 · Goulaouic et al. · 2021 [cited by applicant]
US 20210032354A1 · Staudinger et al. · 2021 [cited by applicant]
US 20210087284A1 · Xu et al. · 2021 [cited by applicant]
US 20210322546A1 · Pirozzi et al. · 2021 [cited by applicant]
US 20210380705A1 · Amin et al. · 2021 [cited by applicant]
US 20220169739A1 · Xu et al. · 2022 [cited by applicant]
US 20220204631A1 · Mannent et al. · 2022 [cited by applicant]
US 20230146317A1 · Stjepanovic et al. · 2023 [cited by applicant]
US 20230183362A1 · Laws et al. · 2023 [cited by applicant]
US 20230340101A1 · Haddad et al. · 2023 [cited by applicant]
US 20240199751A1 · Ardeleanu et al. · 2024 [cited by applicant]
US 20240360232A1 · Abdulai et al. · 2024 [cited by applicant]
AU 2009231482A1 · 2009 [cited by applicant]
CA 2737044A1 · 2010 [cited by applicant]
CN 101522716A · 2009 [cited by applicant]
CN 102046658A · 2011 [cited by applicant]
CN 102197052A · 2011 [cited by applicant]
CN 105517570A · 2016 [cited by applicant]
CN 106232140A · 2016 [cited by applicant]
CN 107206073A · 2017 [cited by applicant]
EP 1229034B1 · 2005 [cited by applicant]
EP 1113818B1 · 2006 [cited by applicant]
EP 1527100B1 · 2009 [cited by applicant]
EP 1283851B1 · 2012 [cited by applicant]
EP 2888281A1 · 2015 [cited by applicant]
EP 2970460A2 · 2016 [cited by applicant]
EP 3010539A1 · 2016 [cited by applicant]
EP 3107575A1 · 2016 [cited by applicant]
EP 3218412A1 · 2017 [cited by applicant]
EP 3470432A1 · 2019 [cited by applicant]
EP 3613432A1 · 2020 [cited by applicant]
EP 3703818A1 · 2020 [cited by applicant]
EP 3962515A1 · 2022 [cited by applicant]
JP 2012507294A · 2012 [cited by applicant]
JP 2015527364A · 2015 [cited by applicant]
JP 2015528576 · 2015 [cited by applicant]
JP 6463351B2 · 2019 [cited by applicant]
RU 2162711C2 · 2001 [cited by applicant]
RU 2453303C1 · 2012 [cited by applicant]
RU 2674680C2 · 2018 [cited by applicant]
TW 201029664A · 2010 [cited by applicant]
WO WO1992019259A1 · 1992 [cited by applicant]
WO WO1994014975A1 · 1994 [cited by applicant]
WO WO2000016804A1 · 2000 [cited by applicant]
WO WO2003048083A2 · 2003 [cited by applicant]
WO WO2003085089A2 · 2003 [cited by applicant]
WO WO2006003407A2 · 2006 [cited by applicant]
WO WO2006083390A2 · 2006 [cited by applicant]
WO WO2007085815A2 · 2007 [cited by applicant]
WO WO2008116165A2 · 2008 [cited by applicant]
WO WO2009081201A2 · 2009 [cited by applicant]
WO WO2009124954A1 · 2009 [cited by applicant]
WO WO2010065557A2 · 2010 [cited by applicant]
WO WO2011026966A2 · 2011 [cited by applicant]
WO WO2011159821A1 · 2011 [cited by applicant]
WO WO2011156000A2 · 2011 [cited by examiner]
WO WO2012049278A1 · 2012 [cited by examiner]
WO WO2012094643A2 · 2012 [cited by applicant]
WO WO2012177945A2 · 2012 [cited by applicant]
WO WO2013051928A1 · 2013 [cited by applicant]
WO WO2013066780A2 · 2013 [cited by applicant]
WO WO2013155010A1 · 2013 [cited by applicant]
WO WO2014031610A1 · 2014 [cited by applicant]
WO WO2014059178A1 · 2014 [cited by applicant]
WO WO2014164959A2 · 2014 [cited by applicant]
WO WO2014031610A8 · 2014 [cited by applicant]
WO WO2017143270A1 · 2017 [cited by applicant]
WO WO2018102597A1 · 2018 [cited by applicant]
WO WO2018190990A1 · 2018 [cited by applicant]
WO WO2019028367A1 · 2019 [cited by applicant]
WO WO2019089473A1 · 2019 [cited by applicant]
WO WO2019224246A1 · 2019 [cited by applicant]
WO WO2020096381A1 · 2020 [cited by applicant]
WO WO2020135710A1 · 2020 [cited by applicant]
WO WO2020223541A1 · 2020 [cited by applicant]
WO WO2021011614A1 · 2021 [cited by applicant]
WO WO2021119028A1 · 2021 [cited by applicant]
Peters SP, Ferguson G, Deniz Y, Reisner C. Uncontrolled asthma: a review of the prevalence, disease burden and options for treatment. Respir Med. Jul. 2006; 100(7):1139-51. doi: 10.1016/j.rmed.2006.03.031. Epub May 18, … [cited by examiner]
Brandt EB, Sivaprasad U. Th2 Cytokines and Atopic Dermatitis. J Clin Cell Immunol. Aug. 10, 2011;2(3):110. doi: 10.4172/2155-9899.1000110. PMID: 21994899; PMCID: PMC3189506. (Year: 2011). [cited by examiner]
Asthma Medications https://web.archive.org/web/20140122192705/http://www.drugs.com/condition/asthma.html (Year: 2014). [cited by examiner]
Peters et al. Uncontrolled asthma: a review of the prevalence, disease burden and options for treatment. Respir Med. Jul. 2006;100(7):1139-51. doi: 10.1016/j.rmed.2006.03.031 (Year: 2006). [cited by examiner]
Wenzel et al. Dupilumab in Persistent Asthma with Elevated Eosinophil Levels. N Engl J Med 2013;368:2455-66. (Year: 2013). [cited by examiner]
Abonia, et al. (Apr. 2013) “High Prevalence of Eosinophilic Esophagitis in Patients with Inherited Connective Tissue Disorders”, Journal of Allergy and Clinical Immunology, vol. 132, No. 2, pp. 378-386. [cited by applicant]
Aceves, et al. (Feb. 29, 2009) “Relationships Between Eosinophilic Inflammation, Tissue Remodeling and Fibrosis in Eosinophilic Esophagitis”, Immunology and Allergy Clinics of North America, vol. 29, No. 1, pp. 197-211. [cited by applicant]
Alving, et al. (1993) “Increased amount of nitric oxide in exhaled air of asthmatics”, European Respiratory Journal, vol. 6, pp. 1368-1370. [cited by applicant]
“Annual Report 2013”, Receptos Inc., Apr. 2013, 411 Pages. [cited by applicant]
Assa'Ad, et al. (Aug. 10, 2011) “An Antibody Against IL-5 Reduces Numbers of Esophageal Intraepithelial Eosinophils in Children with Eosinophilic Esophagitis”, Gastroenterology, vol. 141, Number 5, pp. 1593-1604. [cited by applicant]
Avdeeva, et al. (Apr. 2018) “Precision Medicine in Chronic Rhinosinusitis with Nasal Polyps”, Current Allergy and Asthma Reports, vol. 18, No. 4, p. 25. [cited by applicant]
Bachert et al., “Burden of Disease on Chronic Rhinosinusitis with Nasal Polyps”, Journal of Asthma and Allergy, 2021, 14: 127-134. [cited by applicant]
Balint, et al. (Dec. 27, 1993) “Antibody Engineering by Parsimonious Mutagenesis”, Gene, vol. 137, Issue 1, pp. 109-118. [cited by applicant]
Barthelemy, “Comprehensive analysis of the factors contributing to the stability and solubility of autonomous human VH domains”, Journal of Biological Chemistry, 2008, 283:3639-3654. [cited by applicant]
Beiboer et al., “Guided selection of a pan carcinoma specific antibody reveals similar binding characteristics yet structural divergence between the original murine antibody and its human equivalent”, Journal of Molecul… [cited by applicant]
Beyer, et al. (Apr. 2, 2002) “Human Milk-Specific Mucosal Lymphocytes of the Gastrointestinal Tract Display a Th2 Cytokine Profile”, Journal of Allergy and Clinical Immunology, vol. 109, Issue 4, pp. 707-713. [cited by applicant]
Bhardwaj, et al. (Sep. 2012) “Biomarkers for Eosinophilic Esophagitis: A Review”, Annals of Allergy, Asthma & Immunology, vol. 109, Issue 3, pp. 155-159. [cited by applicant]
Blanchard, et al. (Apr. 2010) “Coordinate Interaction Between IL-13 and Epithelial Differentiation Cluster Genes in Eosinophilic Esophagitis”, The Journal of Immunology, vol. 184, No. 7 (2010), pp. 4033-4041. [cited by applicant]
Blanchard, et al. (Aug. 24, 2005) “Inhibition of Human Interleukin-13-Induced Respiratory and Oesophageal Inflammation by Anti-Human-Interleukin-13 Antibody (CAT-354)”, Clinical & Experimental Allergy, vol. 35, No. 8, p… [cited by applicant]
Blanchard, et al. (Dec. 2, 2007) “IL-13 Involvement in Eosinophilic Esophagitis: Transcriptome Analysis and Reversibility with Glucocorticoids”, Journal of Allergy and Clinical Immunology, vol. 120, No. 6, pp. 1292-1300. [cited by applicant]
Blanchard, et al. (Feb. 2005) “Eotaxin-3 and a Uniquely Conserved Gene-Expression Profile in Eosinophilic Esophagitis”, The Journal of Clinical Investigation, vol. 116, No. 2, pp. 536-547. [cited by applicant]
Blanchard, et al. (Feb. 2009) “Chemotactic Factors Associated with Eosinophilic Gastrointestinal Diseases”, Immunology and allergy clinics of North America, vol. 29, No. 1, pp. 141-148. [cited by applicant]
Blanchard, et al. (Jan. 1, 2011) “A Striking Local Esophageal Cytokine Expression Profile in Eosinophilic Esophagitis”, Journal of Allergy and Clinical Immunology, vol. 127, No. 1, pp. 208-217. [cited by applicant]
Blankestijn et al., “Could Duratumumab be used to treat severe allergy?”, Journal of Allergy and Clinical Immunology, vol. 139, No. 5, Jan. 19, 2017, p. 1677-1678.e3. [cited by applicant]
Brahmer, et al., “Safety and Activity of Anti-PD-L1 Antibody in Patients With Advanced Cancer”, New England Journal of Medicine, vol. 366, pp. 2455-2465, Jun. 28, 2012. [cited by applicant]
Buddenkotte et al., “Pathophysiology and therapy of pruritis in allergic and atopic diseases”, Allergy 65 (2010), 805-821. [cited by applicant]
Carr, Topical Calcineurin Inhibitors for Atopic Dermatitis: Review and Treatment Recommendations, Pediatric Drugs, 2013, vol. 15, pp. 303-310. [cited by applicant]
Carter, Paul J. (May 2006) “Potent Antibody Therapeutics by Design”, Nature Reviews Immunology, vol. 6, No. 5, pp. 343-357. [cited by applicant]
Castro et al. (Jun. 28, 2018) “Dupilumab Efficacy and Safety in Moderate-to-Severe Uncontrolled Asthma”, New England Journal of Medicine, vol. 378, No. 26, pp. 2486-2496. [cited by applicant]
Castro et al. (Nov. 1, 2018) “Dupilumab Efficacy and Safety in Uncontrolled, Moderate-to-Severe Allergic Asthma in the Phase 3 Liberty Asthma Quest Study”, Annals of Allergy, Asthma and Immunology, p. S8. [cited by applicant]
Chan et al. (Jun. 2009) “An update on the classifications, diagnosis, and treatment of rhinosinusitis”, Current Opinion in Otolaryngology & Head and Neck Surgery, vol. 17, Issue 3, pp. 204-208. [cited by applicant]
Chehade, et al. (Feb. 2009) “The Role of Lymphocytes in Eosinophilic Gastrointestinal Disorders”, Immunology and Allergy Clinics of North America, vol. 29, Issue 1, pp. 149-158. [cited by applicant]
Chin et al., “Nasal polyposis: an inflammatory condition requiring effective anti-inflammatory treatment”, Current Opinion in Otolaryngology & Head and Neck Surgery, Feb. 2013, 21(1): 23-30. [cited by applicant]
Choi et al., “Predicting antibody complementarity determining region structures without classification”, Molecular Biosystems, 2011, 7:3327-334. [cited by applicant]
Cleveland Clinic (Feb. 2017) “Nasal Polyps”, Nasal Polyps: Symptoms, Causes, Prevention and Treatment, pp. 1-6. [cited by applicant]
ClinicalTrials.gov Identifier: NTC02407756, Last Update posted Aug. 22, 2016, A Study to Determine the Safety and Tolerability of Dupilumab (REGN668/SAR231893) in Patients Aged >6 to <18 Years With Atopic Dermatitis (Ec… [cited by applicant]
Colice, et al. (Aug. 2004) “Categorizing Asthma Severity: An Overview of National Guidelines”, Clinical Medicine & Research, vol. 2, No. 3, pp. 155-163. [cited by applicant]
Cork et al., An open-label phase lla trial assessing the pharmacokinetics, safety and efficacy of dupilumab in a paediatric population with moderate-to-severe atopic dermatitis, P94, British Association of Dermatologist… [cited by applicant]
Corren et al. (2010) “A Randomized, Controlled, Phase 2 Study of AMG 317, an IL-4R Antagonist, in Patients with Asthma,” Am. J. Respir. Crit. Care Med. 181(8):788-796. [cited by applicant]
Corren et al. (Nov. 1, 2019) “D201 Dupilumab Efficacy in Patients with Uncontrolled, Moderate-to-Severe Asthma and Serologic Evidence of Allergic Bronchopulmonary Aspergillosis”, Annals of Allergy, vol. 123, No. 5. [cited by applicant]
Darsow et al., “Pruritus and Atopic Dermatitis”, Clinic Rev Allerg Immunol (2011) 41:237-244. [cited by applicant]
Davis, et al. (Aug. 2004) “The Evolutionary and Structural ‘Logic’ of Antigen Receptor Diversity”, Seminars in Immunology, vol. 16, Issue 4, pp. 239-243. [cited by applicant]
De Genst et al., “Antibody repertoire development in camelids”, Developmental and Comparative Immunology, 30 (2006); 187-198. [cited by applicant]
Dellon, Evan S. (Apr. 27, 2013) “The Pathogenesis of Eosinophilic Esophagitis: Beyond the Eosinophil”, Digestive Diseases and Sciences, vol. 58, pp. 1445-1448. [cited by applicant]
Desreumaux, et al. (Mar. 1, 1996) “Interleukin 3, Granulocyte-Macrophage Colony-Stimulating Factor, and Interleukin 5 in Eosinophilic Gastroenteritis”, Gastroenterology, vol. 110, No. 3, pp. 768-774. [cited by applicant]
Djukanovic, et al. (2002) “Standardised Methodology of Sputum Induction and Processing”, European Respiratory Journal, pp. 1S-2S. [cited by applicant]
Dupixent (dupilumab) Injection, for Subcutaneous Use, Patient Information, Issued Mar. 2017, 34 pages. [cited by applicant]
“Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma”, National Heart, Blood and Lung Institute, NIH, Aug. 28, 2007, 440 Pages. [cited by applicant]
Extended European Search Report received for European Application No. 19187112.8, mailed on Jan. 23, 2020, 13 Pages. [cited by applicant]
Extended European Search Report for European Patent Application No. 21191120.1, mailed Mar. 2, 2022. [cited by applicant]
Extended European Search Report for European Patent Application No. 21199451.2, mailed May 9, 2022. [cited by applicant]
Fillon, et al. (2009) “Epithelial Function in Eosinophilic Gastrointestinal Diseases”, Immunology and Allergy Clinics of North America, vol. 29, No. 1, pp. 171-178. [cited by applicant]
Foroughi, et al. (Sep. 1, 2007) “Anti-IgE Treatment of Eosinophil-Associated Gastrointestinal Disorders”, Journal of Allergy and Clinical Immunology, vol. 120, Issue 3, pp. 594-601. [cited by applicant]
Franciosi, et al. (Feb. 2009) “Eosinophilic Esophagitis”, Immunology and Allergy Clinics of North America, vol. 29, Issue 1, pp. 19-27. [cited by applicant]
Frieri, Marianne (Mar. 28, 2014) “Asthma Linked with Rhinosinusitis: An Extensive Review”, Allergy & Rhinology (Providence), vol. 5, No. 1, pp. e41-e49. [cited by applicant]
Frois et al. (2009) “Inhaled corticosteroids or long-acting beta-agonists alone or in fixed-dose combinations in asthma treatment: a systematic review of fluticasone/budesonide and formoterol/salmeterol,” Clinical Thera… [cited by applicant]
Green, et al. (2012) “Molecular Cloning: A Laboratory Manual”, Cold Spring Harbor Laboratory Press, Fourth Edition, 34 Pages. [cited by applicant]
Griffiths et al., “Human anti-self antibodies with high specificity from phage display libraries”, The EMBO Journal, 1993, 12:725-734. [cited by applicant]
Hambly, et al., “Monoclonal Antibodies for the Treatment of Refractory Asthma”, Current Opinion in Pulmonary Medicine, vol. 20, Issue 1, pp. 87-94, Jan. 2014. [cited by applicant]
Healio Gastroenterology, “Novel therapy improved disease features in EoE”, Oct. 8, 2019, located online at: https://www.healio.com/news/gastroenterology/20191008/novel-therapy-improves-disease-features-in-eoe, 2 pages. [cited by applicant]
Healthline website (Jan. 25, 2021) “Nasal Polyps”, Nasal Polyps: Causes, Symptoms, and Diagnosis, pp. 1-11. [cited by applicant]
Hijnen, et al. (Feb. 2004) “Serum Thymus and Activation-Regulated Chemokine (TARC) and Cutaneous T Cell-Attracting Chemokine (CTACK) Levels in Allergic Diseases”, Journal of Allergy and Clinical Immunology, vol. 113, No… [cited by applicant]
Hirano et al., “Efficacy of Dupilumab in a Phase 2 Randomized Trial of Adults with Active Eosinophilic Esophagitis”, Gastroenterology 2020; 158: 111-122. [cited by applicant]
Hong et al. (2011) “Management of Itch in Atopic Dermatitis,” Semin. Cutan. Med. Surg. 30(2):71-86. [cited by applicant]
International Nonproprietary Names for Pharmaceutical Substances (INN), WHO Drug Information, 2012, vol. 26, No. 4, obtained from url: https://www.who.int/medicines/publications/druginformation/issues/PL_108.pdf. [cited by applicant]
“International Nonproprietary Names for Pharmaceutical Substances (INN)”, WHO Drug Information records—World Health Organization, Jan. 1, 2014, pp. 379-422. [cited by applicant]
International Search Report and Written Opinion for PCT International Patent Application No. PCT/US2018/058039, mailed Jan. 28, 2019. [cited by applicant]
International Search Report and Written Opinion for PCT International Patent Application No. PCT/US2020/030824, dated Sep. 1, 2020. [cited by applicant]
Ivashkin, et al. (2012) “Eosinophilic Esophagitis: A Review of the Literature and a Description of its Own Observation”, FUGHC, vol. 22, No. 1, Available at: <<RZHGGK online—www.gastro-j.ru>>, pp. 71-81. [cited by applicant]
Jahnz-Rozyk, et al. (Apr. 6, 2005) “Serum Thymus and Activation-Regulated Chemokine, Macrophage-Derived Chemokine and Eotaxin as Markers of Severity of Atopic Dermatitis”, Allergy, vol. 60, No. 5, pp. 685-688. [cited by applicant]
Jakubke, et al. (1985) “Amino Acids, Peptides, Proteins”, M: Mir, pp. 92-94. [cited by applicant]
Jyonouchi, et al. (2013) “Invariant Natural Killer T cells in children with Eosinophilic Esophagitis”, Basic Mechanisms in Allergic Disease, Clinical & Experimental Allergy, vol. 44, No. 1, pp. 58-68. [cited by applicant]
Kagami, et al. (2003) “Significant Elevation of Serum Levels of Eotaxin-3/CCL26, but not of Eotaxin-2/CCL24, in Patients with Atopic Dermatitis: Serum Eotaxin-3/CCL26 Levels Reflect the Disease Activity of Atopic Dermat… [cited by applicant]
Kakinuma, et al. (2002) “Serum Macrophage-Derived Chemokine (MDC) Levels are Closely Related with the Disease Activity of Atopic Dermatitis”, Clinical & Experimental Immunology, vol. 127, No. 2, pp. 270-273. [cited by applicant]
Kakinuma, et al. (Mar. 1, 2001) “Thymus and Activation-Regulated Chemokine in Atopic Dermatitis: Serum Thymus and Activation-Regulated Chemokine Level is Closely Related with Disease Activity”, Journal of Allergy and Cl… [cited by applicant]
Katial, Rohit (Feb. 2009) “Biomarkers for Nononcologic Gastrointestinal Diseases”, Immunology and Allergy Clinics of North America, vol. 29, Issue 1, pp. 119-127. [cited by applicant]
Kegg Drug: D10354, Dupilumab, originally retrieved on Aug. 16, 2019, obtained from url: https://www.genome.jp/dbget-bin/www_bget?dr:D10354. [cited by applicant]
Kim, et al. (Dec. 1, 2004) “Rebound Eosinophilia after Treatment of Hypereosinophilic Syndrome and Eosinophilic Gastroenteritis with Monoclonal Anti-IL-5 Antibody SCH55700”, Journal of Allergy and Clinical Immunology, v… [cited by applicant]
Klementina, et al. (Mar. 24, 2018) “Precision Medicine in Chronic Rhinosinusitis with Nasal Polyps”, Allergy and Asthma Reports, vol. 18, No. 4, 8 Pages. [cited by applicant]
Klimka et al., “Human anti-CD30 recombinant antibodies by guided phage antibody selection using cell panning”, British Journal of Cancer, 2000, 83:252-260. [cited by applicant]
Konikoff, et al. (Nov. 1, 2006) “A Randomized, Double-Blind, Placebo-Controlled Trial of Fluticasone Propionate for Pediatric Eosinophilic Esophagitis”, Gastroenterology, vol. 131, No. 5, pp. 1381-1391. [cited by applicant]
Kottyan, et al. (Aug. 2014) “Genome-Wide Association Analysis of Eosinophilic Esophagitis Provides Insight into the Tissue Specificity of this Allergic Disease”, Nature Genetics, vol. 46, No. 8, pp. 895-900. [cited by applicant]
Kroegel, et al. (May 2009) “Global Initiative for Asthma (GINA) guidelines: 15 Years of Application”, Expert Review of Clinical Immunology, vol. 5, No. 3, pp. 239-249. [cited by applicant]
Kulis, et al. (Nov. 19, 2010) “Single-Tree Nut Immunotherapy Attenuates Allergic Reactions in Mice with Hypersensitivity to Multiple Tree Nuts”, Journal of Allergy and Clinical Immunology, vol. 127, No. 1, pp. 81-88. [cited by applicant]
Lange et al., “The Sino-Nasal Outcome Test 22 validated for Danish patients”, Dan Med Bull., 2011, 58(2): A4235. [cited by applicant]
Leung, et al. (Apr. 2004) “New Insights into Atopic Dermatitis”, The Journal of Clinical Investigation, vol. 113, No. 5, pp. 651-657. [cited by applicant]
Leung, et al. (Mar. 13, 2003) “Effect of Anti-IgE Therapy in Patients with Peanut Allergy”, New England Journal of Medicine, vol. 348, No. 11, pp. 986-993. [cited by applicant]
Liacouras, et al. (Apr. 8, 2011) “Eosinophilic Esophagitis: Updated Consensus Recommendations for Children and Adults”, Journal of Allergy and Clinical Immunology, vol. 128, No. 1, pp. 3-20. [cited by applicant]
Liu, et al. (Aug. 9, 1999) “Hydrodynamics-Based Transfection in Animals by Systemic Administration of Plasmid DNA”, Gene Therapy, vol. 6, No. 7, pp. 1258-1266. [cited by applicant]
Lommatzsch et al. (Dec. 12, 2014) “Severe Asthma Definiteion, Diagnosis and Treatment”, Deutsches Arzteblatt International Feb. 2013, vol. 111, No. 50, pp. 847-855. [cited by applicant]
Lucendo, et al. (Nov. 1, 2012) “Adult Versus Pediatric Eosinophilic Esophagitis: Important Differences and Similarities for the Clinician to Understand”, Expert Review of Clinical Immunology, vol. 8, No. 8, pp. 733-745. [cited by applicant]
Lwin, et al. (Apr. 2011) “Eosinophilic Gastritis: Histopathological Characterization and Quantification of the Normal Gastric Eosinophil Content”, Modern Pathology, vol. 24, No. 4, pp. 556-563. [cited by applicant]
Maes, et al., “Targeting Interleukin-4 in Asthma: Lost in Translation?”, American Journal of Respiratory Cell and Molecular Biology, vol. 47, pp. 261-270, 2012. [cited by applicant]
Mannon, et al. (2012) “Interleukin 13 and its Role in Gut Defence and Inflammation”, Gut, vol. 61, No. 12, pp. 1765-1773. [cited by applicant]
Masterson, et al. (Oct. 2011) “Update on Clinical and Immunological Features of Eosinophilic Gastrointestinal Diseases”, Current Opinion in Gastroenterology, vol. 27, No. 6, pp. 515-522. [cited by applicant]
Mayo Clinic (Jan. 25, 2021) “Nasal Polyps”, Nasal Polyps—Symptoms and Causes, pp. 1-4. [cited by applicant]
Mayo Foundation for Medical Education and Research (MFMER), “Chronic Sinusitis”, Aug. 1, 2020. [cited by applicant]
Mendelsohn, et al., “Revision Rates after Endoscopic Sinus Surgery: A Recurrence Analysis”, Annals of Otology, Rhinology & Laryngology, vol. 120, No. 3, pp. 162-166., 2011. [cited by applicant]
Mishra, et al. (Jan. 1, 2001) “An Etiological Role for Aeroallergens and Eosinophils in Experimental Esophagitis”, The Journal of Clinical Investigation, vol. 107, No. 1, pp. 83-90. [cited by applicant]
Mishra, et al. (Mar. 1, 2002) “IL-5 Promotes Eosinophil Trafficking to the Esophagus”, The Journal of Immunology, vol. 168, No. 5, pp. 2464-2469. [cited by applicant]
Mishra, et al. (Nov. 1, 2003) “Intratracheal IL-13 Induces Eosinophilic Esophagitis by an IL-5, Eotaxin-1, and STAT6-Dependent Mechanism”, Gastroenterology, vol. 125, No. 5, pp. 1419-1427. [cited by applicant]
Naclerio, et al. (Feb. 1, 2017) “Dupilumab Improves Sense of Smell and Reduces Anosmia Among Patients with Nasal Polyposis and Chronic Sinusitis: Results from a Phase 2a Trial”, Journal of Allergy and Clinical Immunolog… [cited by applicant]
Nadeau, et al. (Jun. 2011) “Rapid Oral Desensitization in Combination with Omalizumab Therapy in Patients with Cow's Milk Allergy”, The Journal of Allergy and Clinical Immunology, vol. 127, No. 6, pp. 1622-1624. [cited by applicant]
Nagaraju et al., “Bortezomib treatment diminishes hazelnut-induced intestinal anaphylaxis in mice: Immunomodulation”, European Journal of Immunology, vol. 46, No. 7, May 11, 2016, pp. 1727-1736. [cited by applicant]
Nguyen, et al. (Jul. 2011) “Immune Modulation for Treatment of Allergic Disease”, Immunological Reviews, vol. 242, No. 1, pp. 258-271. [cited by applicant]
Niederberger, Verena (Feb. 2009) “Allergen Specific Immunotherapy”, Immunology Letters, vol. 122, Issue 2, pp. 131-133. [cited by applicant]
Ohno, et al. (May 1, 1985) “Antigen-Binding Specificities of Antibodies are Primarily Determined by Seven Residues of VH”, Proceedings of the National Academy of Sciences, vol. 82, No. 9, pp. 2945-2949. [cited by applicant]
Ong, Peck Y. (2012) “Editorial Update on Emerging Treatments of Atopic Dermatitis”, Expert Opinion on Emerging Drugs, vol. 17, No. 2, pp. 129-133. [cited by applicant]
Otani, et al. (Apr. 29, 2013) “Anti-IL-5 Therapy Reduces Mast Cell and IL-9 Cell Numbers in Pediatric Patients with Eosinophilic Esophagitis”, Journal of Allergy and Clinical Immunology, vol. 131, Number 6, pp. 1576-158… [cited by applicant]
Oyoshi, et al. (Jan. 1, 2009) “Cellular and Molecular Mechanisms in Atopic Dermatitis”, Advances in Immunology, vol. 102, pp. 135-226. [cited by applicant]
Peserico, et al. (2008) “Reduction of Relapses of Atopic Dermatitis with Methylprednisolone Aceptonate Cream Twice Weekly in Addition to Maintenance Treatment with Enrollment: A Multicentre, Randomized, Double-Blind, Co… [cited by applicant]
Powell, et al. (Sep.-Oct. 1998) “Compendium of Excipients for Parenteral Formulations”, PDA Journal of Pharmaceutical Science and Technology, vol. 52, No. 5, pp. 238-311. [cited by applicant]
Prieto, et al. (May 24, 2013) “Eosinophilic Esophagitis in Adults: An Update on Medical Management”, Current Gastroenterology Reports, vol. 15, No. 6, p. 324. [cited by applicant]
Prussin, et al. (Dec. 1, 2009) “Eosinophilic Gastrointestinal Disease and Peanut Allergy are Alternatively Associated with IL-51 and IL-5—TH2 Responses”, Journal of Allergy and Clinical Immunology, vol. 124, No. 6, pp. … [cited by applicant]
Rafi, et al. (Jan. 1, 2010) “Effects of Omalizumab in Patients with Food Allergy”, In Allergy & Asthma Proceedings, vol. 31, No. 1, pp. 76-83. [cited by applicant]
Rayapudi (Aug. 2010) “Indoor insect Allergens are Potent Inducers of Experimental Eosinophilic Esophagitis in Mice”, Journal of Leukocyte Biology, vol. 88, No. 2, pp. 337-346. [cited by applicant]
Regeneron Pharmaceuticals (Oct. 16, 2017) Regeneron and Sanofi Announce Positive Phase 2 Study Results for Dupilumab in Patients Active Moderate'-to-severe Eosinophilic Esophagitis , Acquire Media, 4 Pages. [cited by applicant]
Rizk, Habib (2011) “Role of Aspirin Desensitization in the Management of Chronic Rhinosinusitis”, Current Opinion in Otolaryngology & Head and Neck Surgery, vol. 19, Issue 3, pp. 210-217. [cited by applicant]
Roll, et al. (Jan. 1, 2006) “Safety of Specific Immunotherapy using a Four-Hour Ultra-Rush Induction Scheme in Bee and Wasp Allergy”, Journal of Investigational Allergology and Clinical Immunology, vol. 16, No. 2, pp. 7… [cited by applicant]
Rothenberg, Marc E. (Jan. 1, 2004) “Eosinophilic Gastrointestinal Disorders (EGID)”, Journal of Allergy and Clinical Immunology, vol. 113, No. 1, pp. 11-28. [cited by applicant]
Rothenberg, Marc E. (Oct. 2009) “Eosinophilic Esophagitis: Biology to Therapy”, Gastroenterology, vol. 137, No. 4, pp. 1238-1249. [cited by applicant]
Sampson, et al. (May 2011) “A Phase II, Randomized, Double-Blind, Parallel-Group, Placebo0controlled Oral Food Challenge Trial of Xolair (Omalizumab) in Peanut Allergy”, The Journal of Allergy and Clinical Immunology, v… [cited by applicant]
Sanofi (43671) “A Controlled Clinical Study of Dupilumab in Patients with Bilateral Nasal Polyps (Sinus-24)”, ClinicalTrials.gov Identifier: NCT02912468, 18 Pages. [cited by applicant]
Sanofi (May 18, 2020) “Evaluation of SAR440340 and as Combination Therapy with Dupilumab in Moderate-to-Severe Asthma Participants”, Clinical Trials Accession No. NCT03387852, Retrieved from: <<https://clinicaltrials.go… [cited by applicant]
Sanofi (Oct. 19, 2018) “Evaluation of Dupilumab in Patients with Severe Steroid Dependent Asthma (Venture)”, Archive History for NCT02528214, Retrieved at url: <<https://clinicaltrials.gov/ct2/history/NCT02528214?V_38=V… [cited by applicant]
Schmitt, et al. (Dec. 1, 2007) “What are the Best Outcome Measurements for Atopic Eczema? A Systematic Review”, Journal of Allergy and Clinical Immunology, vol. 120, No. 6, pp. 1389-1398. [cited by applicant]
Schneider, et al. (Dec. 1, 2002) “A Pilot Study of Omalizumab to Facilitate Rapid Oral Desensitization in High-Risk Peanut-Allergic Patients”, Journal of Allergy and Clinical Immunology, vol. 132, No. 6, pp. 1368-1374. [cited by applicant]
“Section 3, The Four Components of Asthma Management”, Guidelines for the Diagnosis and Management of Asthma, Aug. 28, 2007, 1 Page. [cited by applicant]
Sefton, MV (Jan. 1, 1987) “Implantable Pumps”, Critical Reviews in Biomedical Engineering, vol. 14, No. 3, pp. 201-240. [cited by applicant]
Sigfried et al., (2019) “Use of Dupilimab in pediatric atopic dermatits: Access, dosing, and implications for managing severe atopic dermatits”, Pediatric Dermatology, 36: 172-176. [cited by applicant]
Sriaroon et al. (Aug. 17, 2014) “Biological Modulators in Eosinophilic Diseases”, Clinical Reviews in Allergy and Immunology, vol. 50, No. 2, pp. 252-272. [cited by applicant]
Stein, et al. (Dec. 1, 2006) “Anti-IL-5 (Mepolizumab) Therapy for Eosinophilic Esophagitis”, Journal of Allergy and Clinical Immunology, vol. 118, No. 6, pp. 1312-1319. [cited by applicant]
Stone, et al. (Dec. 2008) “Immunomodulatory Therapy of Eosinophil-Associated Gastrointestinal Diseases”, Clinical & Experimental Allergy, vol. 38, No. 12, pp. 1858-1865. [cited by applicant]
Straumann, et al. (Feb. 1, 2005) “Eosinophilic Esophagitis: Escalating Epidemiology?”, Journal of Allergy and Clinical Immunology, vol. 115, 2, pp. 418-419. [cited by applicant]
Straumann, et al. (Feb. 1, 2009) “Clinical Evaluation of the Adult who has Eosinophilic Esophagitis”, Immunology and Allergy Clinics of North America, vol. 29, No. 1, pp. 11-18. [cited by applicant]
Straumann, et al. (Jan. 1, 2010) “Anti-Interleukin-5 Antibody Treatment (Mepolizumab) in Active Eosinophilic Oesophagitis: A Randomised, Placebo-Controlled, Double-Blind Trial”, Gut, vol. 59, No. 1, pp. 21-30. [cited by applicant]
Straumman et al. (2008) “Anti-TNF-a (infliximab) therapy for severe adult eosinophilic esophagitis,” J. Allergy Clin. Immunol., 122(2):425-427. [cited by applicant]
Tang, et al. (2010) “YKL-40 in Asthmatic Patients, and its Correlations with Exacerbation, Eosinophils and Immunoglobulin E”, European Respiratory Society, vol. 35, pp. 757-760. [cited by applicant]
Tsubouchi et al. (Jan. 1, 2019) “Successful Treatment with Mepolizumab in a Case of Allergic Bronchopulmonary Aspergillosis Complicated with Nontuberculosis Mycobacterial Infection” Respiratory Medicine CME, vol. 28. [cited by applicant]
US Securities and Exchange Commission Web Site 2019, Form S-1, Dec. 21, 2018, XP055720304, Retrieved from url:<https://www.sec.gov/Archives/edgar/data/1728117/000119312518356444/d626950ds1.htm>. [cited by applicant]
Van Zele et al. (2006) “Differentiation of chronic sinus diseases by measurement of inflammatory mediators,” Allergy. 61:1280-1289. [cited by applicant]
Veerappan, et al. (Apr. 1, 2009) “Prevalence of Eosinophilic Esophagitis in an Adult Population Undergoing Upper Endoscopy: A Prospective Study”, Clinical Gastroenterology and Hepatology, vol. 7, No. 4, pp. 420-426. [cited by applicant]
Vestergaard, et al. (Oct. 1, 2000) “A Th2 Chemokine, TARC, Produced by Keratinocytes May Recruit CLA+CCR4+ Lymphocytes into Lesional Atopic Dermatitis Skin”, Journal of Investigative Dermatology, vol. 115, No. 4, pp. 64… [cited by applicant]
Wang, et al. (Dec. 1, 2008) “The IIL-17 Cytokine Family and their Role in Allergic Inflammation”, Current Opinion in Immunology, vol. 20 Number, pp. 697-702. [cited by applicant]
Ward et al., Binding activities of a repertoire of single immunoglobin variable domains secreted from [cited by applicant]
Wark, et al. (Aug. 7, 2006) “Latest Technologies for the Enhancement of Antibody Affinity”, Advanced Drug Delivery Reviews, vol. 58, No. 5-6, pp. 657-670. [cited by applicant]
Weber, et al. (Mar. 13, 2012) “Anti-IL-4 as a New Strategy in Allergy”, Chemical immunology and Allergy, vol. 96, pp. 120-125. [cited by applicant]
Weihrauch, et al. (Jul. 1, 2005) “Elevated Serum Levels of CC Thymus and Activation-Related Chemokine (Tarc) in Primary Hodgkin's Disease: Potential for a Prognostic Factor”, Cancer Research, vol. 65, No. 13, pp. 5516-5… [cited by applicant]
Weinbrand-Goichberg, et al. (Jul. 1, 2013) “Eosinophilic Esophagitis: An Immune-Mediated Esophageal Disease”, Immunologic Research, vol. 56, No. 2-3, pp. 249-260. [cited by applicant]
Wenzel et al. (2007) “Effect of an interleukin-4 variant on late phase asthmatic response to allergen challenge in asthmatic patients: results of two phase 2a studies,” The Lancet. 370(9596):1422-1431. [cited by applicant]
Wershil, Barry K. (Feb. 1, 2009) “Exploring the Role of Mast Cells in Eosinophilic Esophagitis”, Immunology and Allergy Clinics of North America, vol. 29, No. 1, pp. 189-195. [cited by applicant]
Whalley, et al. (Feb. 2004) “A New Instrument for Assessing Quality of Life in Atopic Dermatitis: International Development of the Quality of Life Index for Atopic Dermatitis (Qoliad)”, British Journal of Dermatology, v… [cited by applicant]
“WHO Drug Information”, 2012, vol. 26, No. 4, Proposed INN: List 108, p. 412. [cited by applicant]
Wilhelm, et al. (Nov. 28, 2011) “Innate Lymphoid Cells and Type 2 (TH2) Mediated Immune Responses—Pathogenic or Beneficial?”, Frontiers in Immunology, vol. 2, Article 68, pp. 1-4. [cited by applicant]
Winter et al., “Pathogenic Long-Lived Plasma Cells and Their Survival Niches in Autoimmunity, Malignancy, and Allergy”, The Journal of Immunology, vol. 189, No. 11, Nov. 19, 2012, pp. 5105-5111. [cited by applicant]
Yasuhara, et al. (Jul. 2010) “Fundamentals of Clinical Pharmacokinetics”, Clinical Pharmacology, vol. 41, Issue 4, pp. 155-158. [cited by applicant]
Zhu et al., “Potential New Targets for Drug Development in Severe Asthma”, World Allergy Organization Journal, Oct. 25, 2018, 11(30): 1-9. [cited by applicant]
Barnes, “Scientific rationale for inhaled combination therapy with long-acting β2-agonists and corticosteroids”, The European Respiratory Journal, Jan. 2002, 19(1): 182-191. [cited by applicant]
Gibaldi, “Biopharmaceutics and Clinical Pharmacokinetics”, 4th Edition, 1991, Lea & Febiger, pp. 12-13, cited in Opposition against European Patent No. 3107575 (EP Application No. 15708991.3), filed on May 4, 2022, on b… [cited by applicant]
International Nonproprietary Names for Pharmaceutical Substances (INN), pp. 401, 402 and 412 of WHO Drug Information, 2012, 26(4):401-471, cited in Annex to the Notice of Opposition against European Patent No. 3107575 (… [cited by applicant]
Chapter 19, “Dosage regimens”, of Aulton's Pharmaceutics: The Science of Dosage Form Design, 2nd Edition, 2001, cited in Annex to the Notice of Opposition against European Patent No. 3107575 (EP Application No. 15708991… [cited by applicant]
Panaccione et al., “Optimal use of biologics in the management of Crohn's disease”, Ther. Adv. Gastroenterol., 2010, 3(3):179-189, which is a review article relating to the optimal use of biologics in the inflammatory d… [cited by applicant]
Global Initiative for Asthma, pp. 29 to 31 and 58 of the Global Strategy for Asthma Management and Prevention, 2009, cited in Annex to the Notice of Opposition against European Patent No. 3107575 (EP Application No. 157… [cited by applicant]
Brusselle et al., “Targeting Immune Pathways for Therapy in Asthma and Chronic Obstructive Pulmonary Disease”, Ann Am Thorac Soc, 2014, 11(Suppl. 5): S322-S328, cited in Notice of Opposition against European Patent No. … [cited by applicant]
Liang et al., “Moderate Accuracy of Peripheral Eosinophil Count for Predicting Eosinophilic Phenotype in Steroid-Naïve Non-Atopic Adult Asthmatics”, Intern Med., 2012, 51: 717-722, cited in Notice of Opposition against … [cited by applicant]
Notice of Opposition against European Patent No. 3470432 (Application No. 18194745.8) filed on Jul. 5, 2022, on behalf of Secerna LLP. [cited by applicant]
D1—Wenzel, Severe Asthma: from characteristics to phenotypes to endotypes (review), Clinical & Experimental Allergy, Jan. 18, 2012, 42: 650-658, cited in Notice of Opposition against European Patent No. 3470432 (Applica… [cited by applicant]
D2—Wenzel, Asthma phenotypes: the evolution from clinical to molecular approaches (review), Nature Medicine, May 4, 2012, 18(5): 716-725, cited in Notice of Opposition against European Patent No. 3470432 (Application No… [cited by applicant]
D3—GINA Report Dec. 2011, Global Strategy for Asthma Management and Prevention, GINA ©2011 & Global Initiative for Asthma, reprinted with permission, Available from www.ginasthma org, cited in Notice of Opposition again… [cited by applicant]
D4—GINA Report Dec. 2012, Global Strategy for Asthma Management and Prevention, GINA @2012 & Global Initiative for Asthma, reprinted with permission, Available from www.ginasthma.org, cited in Notice of Opposition again… [cited by applicant]
D5—Wenzel et al., Dupilumab in persistent asthma with elevated eosinophil levels, N Engl J Med., May 21, 2013, 368(26):2455-2466, cited in Notice of Opposition against European Patent No. 3470432 (Application No. 181947… [cited by applicant]
D6—Protocol for: Wenzel et al., Dupilumab in persistent asthma with elevated eosinophil levels, N Engl J Med., May 21, 2013, 368(26): 2455-2466, cited in Notice of Opposition against European Patent No. 3470432 (Applica… [cited by applicant]
D8—U.S. Pat. No. 8,075,887 B2, High Affinity Human Antibodies to Human IL-4 Receptor, issued Dec. 13, 2011, cited in Notice of Opposition against European Patent No. 3470432 (Application No. 18194745.8) filed on Jul. 5,… [cited by applicant]
D9—PCT International Publication No. WO 2010/053751 A1, High Affinity Human Antibodies to Human IL-4 Receptor, published May 14, 2010, cited in Notice of Opposition against European Patent No. 3470432 (Application No. 1… [cited by applicant]
D10—Study NCT01312961 (v31), Efficacy, Safety, and Tolerability of SAR231893 (REGN668) in Patients with Persistent Moderate to Severe Eosinophilic Asthma, Aug. 20, 2012, cited in Notice of Opposition against European Pa… [cited by applicant]
D11—Press release: Regeneron reports fourth quarter and full year 2011 financial and operating results, Feb. 13, 2012, https://investor.regeneron.com/news-releases/news-release-details/regeneron-reports-fourth-quarter-a… [cited by applicant]
D12—Otulana et al., A Phase 2b Study of Inhaled Pitrakinra, an IL-4 / IL-13 antagonist, successfully identified responder subpopulations of patients with uncontrolled asthma, American Journal of Respiratory and Critical… [cited by applicant]
D13—Corren et al., A randomized, controlled, Phase 2 study of AMG 317, an IL-4Ra antagonist, in patients with asthma, Am J Respir Crit Care Med., Jan. 7, 2010, 181(8):788-796, cited in Notice of Opposition against Europ… [cited by applicant]
D14—Hashimoto & Bel, Targeting IL-5 in severe asthma: a Dream come true?, The Lancet, Aug. 8, 2012, 380(9842): 626-627, cited in Notice of Opposition against European Patent No. 3470432 (Application No. 18194745.8) file… [cited by applicant]
D15—Pavord al., Mepolizumab for severe eosinophilic asthma (Dream): a multicentre, double-blind, placebo-controlled trial, Lancet, Aug. 18, 2012; 380: 651-659, cited in Notice of Opposition against European Patent No. 3… [cited by applicant]
D16—Szefler et al., Asthma Outcomes: Biomarkers, J Allergy Clin Immunol., Mar. 1, 2012, 129: S9-23, cited in Notice of Opposition against European Patent No. 3470432 (Application No. 18194745.8) filed on Jul. 5, 2022, o… [cited by applicant]
D17—Spector & Tan, Is a single blood eosinophil count a reliable marker for “eosinophilic asthma?”, Journal of Asthma, Aug. 20, 2012, 49.8: Early Online: 1-4, cited in Notice of Opposition against European Patent No. 34… [cited by applicant]
D18—WHO Drug Information, vol. 26, No.4, p. 412, Dec. 9, 2012, cited in Notice of Opposition against European Patent No. 3470432 (Application No. 18194745.8) filed on Jul. 5, 2022, on behalf of Secerna LLP. [cited by applicant]
D19—Firszt & Kraft, Pharmacotherapy of Severe Asthma, Curr Opin Pharmacol., Jun. 2010, 10(3): 266-271, cited in Notice of Opposition against European Patent No. 3470432 (Application No. 18194745.8) filed on Jul. 5, 2022… [cited by applicant]
D20—Darveax & Busse, Biologics in asthma—the next step to personalised treatment, J Allergy Clin Immunol Pract., Mar.-Apr. 2015, 3(2): 152-161, cited in Notice of Opposition against European Patent No. 3470432 (Applicat… [cited by applicant]
D21—Eisenstein, Something new under the skin, Nature Biotechnology, Feb. 7, 2011, 29(2): 107-109, cited in Notice of Opposition against European Patent No. 3470432 (Application No. 18194745.8) filed on Jul. 5, 2022, on … [cited by applicant]
D22—Chapter 19, “Dosage regimens” of Aulton's Pharmaceutics: The Science of Dosage Form Design, 2nd Edition, 2001, cited in Notice of Opposition against European Patent No. 3470432 (Application No. 18194745.8) filed on … [cited by applicant]
Notice of Opposition against European Patent No. 3470432 (Application No. 18194745.8) filed on Jul. 5, 2022, on behalf of Dr. Hans Ulrich Dorries. [cited by applicant]
P6—French Patent Application No. 1356994, filed Jul. 16, 2013, cited in Notice of Opposition against European Patent No. 3470432 (Application No. 18194745.8) filed on Jul. 5, 2022, on behalf of Dr. Hans Ulrich Dorries. [cited by applicant]
PA—PCT International Publication No. 2014/031610 A1 published Feb. 27, 2014, cited in Notice of Opposition against European Patent No. 3470432 (Application No. 18194745.8) filed on Jul. 5, 2022, on behalf of Dr. Hans Ul… [cited by applicant]
D1—Wenzel et al., Dupilumab in persistent asthma with elevated eosinophil levels, N Engl J Med., May 21, 2013, 368(26): 2455-2466, cited in Notice of Opposition against European Patent No. 3470432 (Application No. 18194… [cited by applicant]
D2—WHO Drug Information, vol. 26, No.4, pp. 401-471, Proposed INN: List 108, Dec. 9, 2012, cited in Notice of Opposition against European Patent No. 3470432 (Application No. 18194745.8) filed on Jul. 5, 2022, on behalf … [cited by applicant]
D4—Corren et al., A randomized, controlled, Phase 2 study of AMG 317, an IL-4Ra antagonist, in patients with asthma, Am J Respir Crit Care Med., Jan. 7, 2010, 181(8):788-796, cited in Notice of Opposition against Europe… [cited by applicant]
D5—PCT International Publication No. WO 2010/053751 A1, High Affinity Human Antibodies to Human IL-4 Receptor, published May 14, 2010, cited in Notice of Opposition against European Patent No. 3470432 (Application No. 1… [cited by applicant]
D6—Gibaldi, Biopharmaceutics and Clinical Pharmakokinetics, 4 [cited by applicant]
Notice of Opposition against European Patent No. 3470432 (Application No. 18194745.8) filed on Jul. 6, 2022, on behalf of D. Young & Co. [cited by applicant]
D1—Corren et al., A randomized, controlled, Phase 2 study of AMG 317, an IL-4Ra antagonist, in patients with asthma, Am J Respir Crit Care Med., Jan. 7, 2010, 181(8):788-796, cited in Notice of Opposition against Europe… [cited by applicant]
D2—pp. 17, 28, 32, 34, 59 and 61 of the Global Initiative for Asthma: Global Strategy for Asthma Management and Prevention, 2009, cited in Notice of Opposition against European Patent No. 3470432 (Application No. 181947… [cited by applicant]
D4—U.S. Pat. No. 8,075,887 B2, High Affinity Human Antibodies to Human IL-4 Receptor, issued Dec. 13, 2011, cited in Notice of Opposition against European Patent No. 3470432 (Application No. 18194745.8) filed on Jul. 6,… [cited by applicant]
D5—Chapter 19, Dosage Regimens, Alton's Pharmaceutics: The Science of Dosage Form Design, 2 [cited by applicant]
D7—Panaccione and Ghosh, Ther Adv Gastroenterol., 2010, 3(3): 179-189, cited in Notice of Opposition against European Patent No. 3470432 (Application No. 18194745.8) filed on Jul. 6, 2022, on behalf of D. Young & Co. [cited by applicant]
Notice of Opposition against European Patent No. 3470432 (Application No. 18194745.8) filed on Jul. 6, 2022, on behalf of Ms. Regina Neuefeind. [cited by applicant]
A—PCT International Publication No. 2014/031610 published Feb. 27, 2014, cited in Notice of Opposition against European Patent No. 3470432 (Application No. 18194745.8) filed on Jul. 6, 2022, on behalf of Ms. Regina Neue… [cited by applicant]
D1—Brusselle and Bracke, Ann Am Thorac Soc., 2014, 11(Suppl. 5): S322-S328, cited in Notice of Opposition against European Patent No. 3470432 (Application No. 18194745.8) filed on Jul. 6, 2022, on behalf of Ms. Regina N… [cited by applicant]
D2—Woodruff et al., Am J Respir Crit Care Med., 2009, 180: 388-395, cited in Notice of Opposition against European Patent No. 3470432 (Application No. 18194745.8) filed on Jul. 6, 2022, on behalf of Ms. Regina Neuefeind. [cited by applicant]
D3—Liang et al., Intern Med., 2012, 51: 717-722, cited in Notice of Opposition against European Patent No. 3470432 (Application No. 18194745.8) filed on Jul. 6, 2022, on behalf of Ms. Regina Neuefeind. [cited by applicant]
D4—Gibson, Aust Prescr, 1996, 19: 44-47, cited in Notice of Opposition against European Patent No. 3470432 (Application No. 18194745.8) filed on Jul. 6, 2022, on behalf of Ms. Regina Neuefeind. [cited by applicant]
D5—WHO Drug Information, vol. 26, No. 4, p. 412, 2012, cited in Notice of Opposition against European Patent No. 3470432 (Application No. 18194745.8) filed on Jul. 6, 2022, on behalf of Ms. Regina Neuefeind. [cited by applicant]