IP Library › Granted Patent US 12,655,159
Granted Patent B2
US 12,655,159 · App. 18/008,083 · Granted Jun 16, 2026

Deuterated IRAK degraders and uses thereof

Inventor: Xiaozhang Zheng (Lexington, MA)
Assignee: Kymera Therapeutics, Inc.
C07D519/00
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 12,655,159
App. No.
18/008,083
Granted
Jun 16, 2026
Kind
B2
Abstract

The present invention provides deuterium-enriched compounds, compositions thereof, and methods of using the same.

Claims (443)

1 . A compound of formula I:

or a pharmaceutically acceptable salt thereof, wherein:

each of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 , R 20 , R 21 , R 22 , R 23 , R 24 , R 25 , R 26 , R 27 , R 28 , R 29 , R 30 , R 31 , R 32 , R 33 , R 34 , R 35 , R 36 , R 37 , R 38 , R 39 , R 40 , R 41 , R 42 , R 43 , R 44 , R 45 , R 46 , R 47 , R 48 , and R 49 is independently H or D,

provided that at least two of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 , R 20 , R 21 , R 22 , R 23 , R 24 , R 25 , R 26 , R 27 , R 28 , R 29 , R 30 , R 31 , R 32 , R 33 , R 34 , R 35 , R 36 , R 37 , R 38 , R 39 , R 40 , R 41 , R 42 , R 43 , R 44 , R 45 , R 46 , R 47 , R 48 , and R 49 is D.

2 . The compound of claim 1 , wherein at least one of R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 , R 20 , R 21 , R 22 , R 23 , R 24 , R 25 , R 26 , R 27 , R 28 , R 29 , R 30 , R 31 , R 32 , R 33 , R 34 , and R 35 is D.

3 . The compound of claim 1 or 2 , wherein R 6 is D.

4 . The compound of claim 1 or 2 , wherein one or more of R 7 , R 8 , and R 9 is D.

5 . The compound of claim 1 or 2 , wherein R 10 , R 11 , and R 12 is D.

6 . The compound of claim 1 or 2 , wherein R 36 is D.

7 . The compound of claim 1 or 2 , wherein R 39 is D.

8 . The compound of claim 1 or 2 , wherein one or more of R 40 and R 41 is D.

9 . The compound of claim 1 or 2 , wherein at least one of R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 , R 20 , R 21 , R 22 , R 23 , R 24 , R 25 , R 26 , R 27 , R 28 , R 29 , R 30 , R 31 , R 32 , R 33 , R 34 , and R 35 has a % deuterium incorporation of about 50% or greater.

10 . The compound of claim 1 or 2 , wherein at least one of R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 , R 20 , R 21 , R 22 , R 23 , R 24 , R 25 , R 26 , R 27 , R 28 , R 29 , R 30 , R 31 , R 32 , R 33 , R 34 , and R 35 has a % deuterium incorporation of about 80% or greater.

11 . The compound of claim 1 or 2 , wherein at least one of R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 , R 20 , R 21 , R 22 , R 23 , R 24 , R 25 , R 26 , R 27 , R 28 , R 29 , R 30 , R 31 , R 32 , R 33 , R 34 , and R 35 has a % deuterium incorporation of about 90% or greater.

12 . The compound of claim 1 or 2 , wherein each of R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 , R 20 , R 21 , R 22 , R 23 , R 24 , R 25 , R 26 , R 27 , R 28 , R 29 , R 30 , R 31 , R 32 , R 33 , R 34 , and R 35 has a % deuterium incorporation of about 95% or greater.

13 . The compound of claim 1 or 2 , wherein the compound is represented by Formula I-a, I-b, I-c, I-d, I-e, I-f, I-g, I-h, or I-i:

or a pharmaceutically acceptable salt thereof.

14 . The compound of claim 1 or 2 , wherein each of R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 36 , R 39 , R 40 , and R 41 is as defined in an entry set forth below:

Entry

R 6

R 7

R 8

R 9

R 10

R 11

R 12

R 36

R 39

R 40

R 41

i

D

D

D

D

H

H

H

H

H

H

H

ii

D

H

H

H

D

D

D

H

H

H

H

iii

D

H

H

H

H

H

H

D

H

H

H

iv

D

H

H

H

H

H

H

H

D

H

H

v

D

H

H

H

H

H

H

H

H

D

D

vi

H

D

D

D

D

D

D

H

H

H

H

vii

H

D

D

D

H

H

H

D

H

H

H

viii

H

D

D

D

H

H

H

H

D

H

H

ix

H

D

D

D

H

H

H

H

H

D

D

x

H

H

H

H

D

D

D

D

H

H

H

xi

H

H

H

H

D

D

D

H

D

H

H

xii

H

H

H

H

D

D

D

H

H

D

D

xiii

H

H

H

H

H

H

H

D

D

H

H

xiv

H

H

H

H

H

H

H

D

H

D

D

xv

H

H

H

H

H

H

H

H

D

D

D

xvi

H

H

H

H

D

D

H

H

H

H

H

xvii

H

H

H

H

H

D

D

H

H

H

H

xviii

H

H

H

H

D

H

D

H

H

H

H

xix

H

H

H

H

D

D

H

D

H

H

H

xx

H

H

H

H

H

D

D

D

H

H

H

xxi

H

H

H

H

D

H

D

D

H

H

H

xxii

H

H

H

H

D

D

H

H

D

H

H

xxiii

H

H

H

H

H

D

D

H

D

H

H

xxiv

H

H

H

H

D

H

D

H

D

H

H

xxv

H

H

H

H

D

D

H

H

H

D

H

xxvi

H

H

H

H

H

D

D

H

H

D

H

xxvii

H

H

H

H

D

H

D

H

H

D

H

xxviii

H

H

H

H

D

D

H

H

H

H

D

xxix

H

H

H

H

H

D

D

H

H

H

D

xxx

H

H

H

H

D

H

D

H

H

H

D

xxxi

H

H

H

H

D

D

H

H

H

D

D

xxxii

H

H

H

H

H

D

D

H

H

D

D

xxxiii

H

H

H

H

D

H

D

H

H

D

D

or a pharmaceutically acceptable salt thereof.

15 . The compound of claim 13 , wherein each position indicated as “D” has a % deuterium incorporation of about 50% or greater.

16 . The compound of claim 13 , wherein each position indicated as “D” has a % deuterium incorporation of about 80% or greater.

17 . The compound of claim 13 , wherein each position indicated as “D” has a % deuterium incorporation of about 90% or greater.

18 . A compound selected from any one of the following:

or a pharmaceutically acceptable salt thereof.

19 . The compound of claim 18 , wherein each position indicated as “D” has a % deuterium incorporation of about 80% or greater.

20 . The compound of claim 18 , wherein each position indicated as “D” has a % deuterium incorporation of about 90% or greater.

21 . The compound of claim 18 , wherein each position indicated as “D” has a % deuterium incorporation of about 95% or greater.

22 . A composition comprising a compound according to claim 1 or claim 2 and a pharmaceutically acceptable carrier or excipient.

23 . The pharmaceutical composition according to claim 22 , further comprising an additional therapeutic agent.

24 . A method of degrading IRAK1, IRAK2 and/or IRAK4 protein kinase in a patient or biological sample comprising administering to said patient, or contacting said biological sample with a compound according to claim 1 or claim 2 , or a pharmaceutical composition thereof.

25 . A method of treating an IRAK4-mediated disorder, disease, or condition in a patient comprising administering to said patient a compound according to claim 1 or claim 2 , or a pharmaceutical composition thereof,

wherein the IRAK4-mediated disorder, disease or condition is an inflammatory disorder,

wherein the inflammatory disorder is selected from the group consisting of ocular allergy, conjunctivitis, keratoconjunctivitis sicca, vernal conjunctivitis, allergic rhinitis, systemic lupus erythematosus, rheumatoid arthritis, scleroderma, dermatomyositis, ulcerative colitis, Crohn's disease, multiple sclerosis, Sjögren's syndrome, interstitial lung fibrosis, psoriatic arthritis, systemic juvenile idiopathic arthritis, aging, asthma, anaphylaxis, Type 1 diabetes, Type 2 diabetes, atopic dermatitis, allergy, dermatitis, hidradenitis suppurativa, peritonitis, rhinitis, dermatitis herpetiformis, urticaria, acute gout, chronic gout, chronic gouty arthritis, psoriasis, juvenile rheumatoid arthritis, and Cryopyrin Associated Periodic Syndrome (CAPS).

26 . The method according to claim 25 , further comprising administration of an additional therapeutic agent.

27 . The method according to claim 25 , wherein the inflammatory disorder is atopic dermatitis or hidradenitis suppurativa.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 2, 2022
From: ZHENG, XIAOZHANG
To: KYMERA THERAPEUTICS, INC.
Reel/Frame 061961/0024 →
Continuity (2)
Provisional Application 63033959 · Jun 3, 2020
Related Publication 20230250110A1 · Aug 10, 2023
References Cited (400)
US 4650750A · Giese · 1987 [cited by applicant]
US 4709016A · Giese · 1987 [cited by applicant]
US 5217866A · Summerton et al. · 1993 [cited by applicant]
US 5360811A · Tegeler et al. · 1994 [cited by applicant]
US 5360819A · Giese · 1994 [cited by applicant]
US 5516931A · Giese et al. · 1996 [cited by applicant]
US 5602273A · Giese et al. · 1997 [cited by applicant]
US 5604104A · Giese et al. · 1997 [cited by applicant]
US 5610020A · Giese et al. · 1997 [cited by applicant]
US 5650270A · Giese et al. · 1997 [cited by applicant]
US 5721246A · Yoshino et al. · 1998 [cited by applicant]
US 6306663B1 · Kenten et al. · 2001 [cited by applicant]
US 6552065B2 · Remiszewski et al. · 2003 [cited by applicant]
US 6559280B2 · Kenten et al. · 2003 [cited by applicant]
US 6627754B2 · Blumenkopf et al. · 2003 [cited by applicant]
US 6949537B2 · Garlich et al. · 2005 [cited by applicant]
US 7041298B2 · Deshaies et al. · 2006 [cited by applicant]
US 7071189B2 · Kawashima et al. · 2006 [cited by applicant]
US 7074620B2 · Kenten et al. · 2006 [cited by applicant]
US 7173015B2 · Schreiber et al. · 2007 [cited by applicant]
US 7208157B2 · Dashaies et al. · 2007 [cited by applicant]
US 7273920B2 · Kenten et al. · 2007 [cited by applicant]
US 7307077B2 · Kawashima et al. · 2007 [cited by applicant]
US 7390799B2 · Bruncko et al. · 2008 [cited by applicant]
US 7402325B2 · Addington · 2008 [cited by applicant]
US 7449458B2 · Bhamidipati et al. · 2008 [cited by applicant]
US 7501496B1 · Endl et al. · 2009 [cited by applicant]
US 7514444B2 · Honigberg et al. · 2009 [cited by applicant]
US 7528143B2 · Noronha et al. · 2009 [cited by applicant]
US 7557210B2 · Singh et al. · 2009 [cited by applicant]
US 7598257B2 · Rodgers et al. · 2009 [cited by applicant]
US 7622496B2 · Larsen et al. · 2009 [cited by applicant]
US 7667039B2 · Garcia-Echeverria et al. · 2010 [cited by applicant]
US 7713943B2 · Klippel-Giese et al. · 2010 [cited by applicant]
US 7781433B2 · Chuckowree et al. · 2010 [cited by applicant]
US 7932260B2 · Fowler et al. · 2011 [cited by applicant]
US 7989622B2 · Bajjalieh et al. · 2011 [cited by applicant]
US 8138347B2 · Knight et al. · 2012 [cited by applicant]
US 8185616B2 · Nagata et al. · 2012 [cited by applicant]
US 8217035B2 · Burger et al. · 2012 [cited by applicant]
US 8338439B2 · Singh et al. · 2012 [cited by applicant]
US 8486941B2 · Burns et al. · 2013 [cited by applicant]
US 8906682B2 · June et al. · 2014 [cited by applicant]
US 9500653B2 · Crews et al. · 2016 [cited by applicant]
US 9632089B2 · Crews et al. · 2017 [cited by applicant]
US 9694084B2 · Bradner et al. · 2017 [cited by applicant]
US 9750816B2 · Bradner et al. · 2017 [cited by applicant]
US 9770512B2 · Bradner et al. · 2017 [cited by applicant]
US 9821068B2 · Bradner et al. · 2017 [cited by applicant]
US 9969710B2 · Jorand-Lebrun et al. · 2018 [cited by applicant]
US 10125114B2 · Bradner et al. · 2018 [cited by applicant]
US 10336744B2 · Harling et al. · 2019 [cited by applicant]
US 10874743B2 · Mainolfi et al. · 2020 [cited by applicant]
US 11065231B2 · Crew et al. · 2021 [cited by applicant]
US 11117889B1 · Mainolfi et al. · 2021 [cited by applicant]
US 11318205B1 · Mainolfi et al. · 2022 [cited by applicant]
US 11352350B2 · Mainolfi et al. · 2022 [cited by applicant]
US 11591332B2 · Weiss et al. · 2023 [cited by applicant]
US 11685750B2 · Zheng · 2023 [cited by examiner]
US 11707457B2 · Weiss · 2023 [cited by applicant]
US 11723980B2 · Mainolfi et al. · 2023 [cited by applicant]
US 11773103B2 · Rong et al. · 2023 [cited by applicant]
US 11779578B2 · Weiss · 2023 [cited by applicant]
US 11807636B2 · Mainolfi et al. · 2023 [cited by applicant]
US 12168057B2 · Mainolfi et al. · 2024 [cited by applicant]
US 12171768B2 · Gollob et al. · 2024 [cited by applicant]
US 12187744B2 · Leong et al. · 2025 [cited by applicant]
US 12258341B2 · Mainolfi et al. · 2025 [cited by applicant]
US 20010053782A1 · Blumenkopf et al. · 2001 [cited by applicant]
US 20020042427A1 · Tang et al. · 2002 [cited by applicant]
US 20020068063A1 · Deshaies et al. · 2002 [cited by applicant]
US 20020183360A1 · Muller et al. · 2002 [cited by applicant]
US 20040029902A1 · Singh et al. · 2004 [cited by applicant]
US 20040048859A1 · Germann et al. · 2004 [cited by applicant]
US 20040106569A1 · Klippel-Giese et al. · 2004 [cited by applicant]
US 20040116421A1 · Kawashima et al. · 2004 [cited by applicant]
US 20040242631A1 · Garlich et al. · 2004 [cited by applicant]
US 20050014802A1 · Attardo et al. · 2005 [cited by applicant]
US 20050075306A1 · Schreiber et al. · 2005 [cited by applicant]
US 20060211657A1 · Singh et al. · 2006 [cited by applicant]
US 20070098719A1 · Smith et al. · 2007 [cited by applicant]
US 20070135461A1 · Rodgers et al. · 2007 [cited by applicant]
US 20070191405A1 · Noronha et al. · 2007 [cited by applicant]
US 20080076768A1 · Chuckowree et al. · 2008 [cited by applicant]
US 20080108636A1 · Honigberg et al. · 2008 [cited by applicant]
US 20080194579A1 · Garcia-Echeverria et al. · 2008 [cited by applicant]
US 20080275067A1 · Fowler et al. · 2008 [cited by applicant]
US 20090055944A1 · Korman et al. · 2009 [cited by applicant]
US 20090136494A1 · Ponath et al. · 2009 [cited by applicant]
US 20090233903A1 · Rodgers et al. · 2009 [cited by applicant]
US 20100087440A1 · Bajjalieh et al. · 2010 [cited by applicant]
US 20100150892A1 · Han · 2010 [cited by applicant]
US 20100197671A1 · Burns et al. · 2010 [cited by applicant]
US 20100197686A1 · Xing et al. · 2010 [cited by applicant]
US 20100203056A1 · Irving et al. · 2010 [cited by applicant]
US 20100233183A1 · Triebel et al. · 2010 [cited by applicant]
US 20100247554A1 · Lemke et al. · 2010 [cited by applicant]
US 20100249092A1 · Singh et al. · 2010 [cited by applicant]
US 20100249126A1 · Burger et al. · 2010 [cited by applicant]
US 20100279316A1 · Gorelik et al. · 2010 [cited by applicant]
US 20110008331A1 · Triebel · 2011 [cited by applicant]
US 20110053941A1 · Mautino et al. · 2011 [cited by applicant]
US 20110136796A1 · Mautino et al. · 2011 [cited by applicant]
US 20110165156A1 · Dimoudis et al. · 2011 [cited by applicant]
US 20110196150A1 · Man et al. · 2011 [cited by applicant]
US 20110223611A1 · Salamone et al. · 2011 [cited by applicant]
US 20110274683A1 · Wong et al. · 2011 [cited by applicant]
US 20120015962A1 · Arora et al. · 2012 [cited by applicant]
US 20120189639A1 · Schebye et al. · 2012 [cited by applicant]
US 20120277217A1 · Mautino et al. · 2012 [cited by applicant]
US 20120283238A1 · Romero et al. · 2012 [cited by applicant]
US 20120329997A1 · Fertig et al. · 2012 [cited by applicant]
US 20130005949A1 · Fertig et al. · 2013 [cited by applicant]
US 20130149236A1 · Johnson et al. · 2013 [cited by applicant]
US 20130190340A1 · Hedstrom et al. · 2013 [cited by applicant]
US 20130231328A1 · Harriman et al. · 2013 [cited by applicant]
US 20130274241A1 · Jorand-Lebrun et al. · 2013 [cited by applicant]
US 20140018343A1 · Romero et al. · 2014 [cited by applicant]
US 20140018357A1 · Harriman et al. · 2014 [cited by applicant]
US 20140018361A1 · Harriman et al. · 2014 [cited by applicant]
US 20140066625A1 · Mautino et al. · 2014 [cited by applicant]
US 20140079699A1 · Wong et al. · 2014 [cited by applicant]
US 20140079706A1 · Cannarile et al. · 2014 [cited by applicant]
US 20140093511A1 · Lonberg et al. · 2014 [cited by applicant]
US 20140155379A1 · Ho et al. · 2014 [cited by applicant]
US 20140194404A1 · McElroy et al. · 2014 [cited by applicant]
US 20140302523A1 · Crews et al. · 2014 [cited by applicant]
US 20140329799A1 · Seganish et al. · 2014 [cited by applicant]
US 20140336363A1 · Fertig et al. · 2014 [cited by applicant]
US 20140341917A1 · Nastri et al. · 2014 [cited by applicant]
US 20140356322A1 · Crews et al. · 2014 [cited by applicant]
US 20150011532A1 · Paidi et al. · 2015 [cited by applicant]
US 20150018344A1 · Paidi et al. · 2015 [cited by applicant]
US 20150025093A1 · Romero et al. · 2015 [cited by applicant]
US 20150045347A1 · Dodd et al. · 2015 [cited by applicant]
US 20150094305A1 · Romero et al. · 2015 [cited by applicant]
US 20150133451A1 · Yoshida et al. · 2015 [cited by applicant]
US 20150141396A1 · Crosignani et al. · 2015 [cited by applicant]
US 20150191464A1 · Santella et al. · 2015 [cited by applicant]
US 20150225410A1 · Castro et al. · 2015 [cited by applicant]
US 20150225449A1 · Donnell et al. · 2015 [cited by applicant]
US 20150274708A1 · Seganish et al. · 2015 [cited by applicant]
US 20150274738A1 · Gray et al. · 2015 [cited by applicant]
US 20150284382A1 · Bhide et al. · 2015 [cited by applicant]
US 20150284405A1 · Trzupek et al. · 2015 [cited by applicant]
US 20150291562A1 · Crew et al. · 2015 [cited by applicant]
US 20150299224A1 · Seganish et al. · 2015 [cited by applicant]
US 20150329498A1 · Romero et al. · 2015 [cited by applicant]
US 20150374678A1 · Chamberlain et al. · 2015 [cited by applicant]
US 20150376167A1 · Jorand-Lebrun et al. · 2015 [cited by applicant]
US 20150376206A1 · Jorand-Lebrun et al. · 2015 [cited by applicant]
US 20160002265A1 · Jenkins et al. · 2016 [cited by applicant]
US 20160022642A1 · Crews et al. · 2016 [cited by applicant]
US 20160045607A1 · Crew et al. · 2016 [cited by applicant]
US 20160058872A1 · Crew et al. · 2016 [cited by applicant]
US 20160145252A1 · Jorand-Lebrun et al. · 2016 [cited by applicant]
US 20160176916A1 · Bradner et al. · 2016 [cited by applicant]
US 20160214972A1 · Jin et al. · 2016 [cited by applicant]
US 20160235730A1 · Bradner et al. · 2016 [cited by applicant]
US 20160235731A1 · Bradner et al. · 2016 [cited by applicant]
US 20160243247A1 · Bradner et al. · 2016 [cited by applicant]
US 20160256468A1 · Schafer et al. · 2016 [cited by applicant]
US 20160272596A1 · Chen et al. · 2016 [cited by applicant]
US 20160272639A1 · Crew et al. · 2016 [cited by applicant]
US 20160311833A1 · Bothe et al. · 2016 [cited by applicant]
US 20160311839A1 · Kelley et al. · 2016 [cited by applicant]
US 20160326151A1 · Gummadi et al. · 2016 [cited by applicant]
US 20160340366A1 · Gummadi et al. · 2016 [cited by applicant]
US 20170001990A1 · Chen et al. · 2017 [cited by applicant]
US 20170008896A1 · Dahmann et al. · 2017 [cited by applicant]
US 20170008904A1 · Crew et al. · 2017 [cited by applicant]
US 20170022189A1 · Zhang · 2017 [cited by applicant]
US 20170037004A1 · Crew et al. · 2017 [cited by applicant]
US 20170065719A1 · Qian et al. · 2017 [cited by applicant]
US 20170121321A1 · Crews et al. · 2017 [cited by applicant]
US 20170152263A1 · Gummadi et al. · 2017 [cited by applicant]
US 20170204093A1 · Chan et al. · 2017 [cited by applicant]
US 20170247388A1 · Altman et al. · 2017 [cited by applicant]
US 20170281784A1 · Wang et al. · 2017 [cited by applicant]
US 20170327469A1 · Crew et al. · 2017 [cited by applicant]
US 20170369476A1 · Chen et al. · 2017 [cited by applicant]
US 20180009779A1 · Bradner et al. · 2018 [cited by applicant]
US 20180015087A1 · Liu et al. · 2018 [cited by applicant]
US 20180051027A1 · Lim et al. · 2018 [cited by applicant]
US 20180051028A1 · Lim et al. · 2018 [cited by applicant]
US 20180051029A1 · Lim et al. · 2018 [cited by applicant]
US 20180051030A1 · Lim et al. · 2018 [cited by applicant]
US 20180051035A1 · Lim et al. · 2018 [cited by applicant]
US 20180085465A1 · Bradner et al. · 2018 [cited by applicant]
US 20180118733A1 · Harling et al. · 2018 [cited by applicant]
US 20180127432A1 · Trzupek et al. · 2018 [cited by applicant]
US 20180134684A1 · Bradner et al. · 2018 [cited by applicant]
US 20180147202A1 · Crew et al. · 2018 [cited by applicant]
US 20180169097A1 · Hammerman et al. · 2018 [cited by applicant]
US 20180186799A1 · Gardner et al. · 2018 [cited by applicant]
US 20180194724A1 · Kemp et al. · 2018 [cited by applicant]
US 20180201609A1 · Gummadi et al. · 2018 [cited by applicant]
US 20180208605A1 · Gummadi et al. · 2018 [cited by applicant]
US 20180228907A1 · Crew et al. · 2018 [cited by applicant]
US 20180230157A1 · Bacon et al. · 2018 [cited by applicant]
US 20180298015A1 · Bryan et al. · 2018 [cited by applicant]
US 20180327419A1 · Bradner et al. · 2018 [cited by applicant]
US 20190071415A1 · Bradner et al. · 2019 [cited by applicant]
US 20190076539A1 · Phillips et al. · 2019 [cited by applicant]
US 20190076540A1 · Phillips et al. · 2019 [cited by applicant]
US 20190076541A1 · Phillips et al. · 2019 [cited by applicant]
US 20190076542A1 · Phillips et al. · 2019 [cited by applicant]
US 20190151295A1 · Crew et al. · 2019 [cited by applicant]
US 20190151457A1 · Bradner et al. · 2019 [cited by applicant]
US 20190192532A1 · Bradner et al. · 2019 [cited by applicant]
US 20190192668A1 · Mainolfi et al. · 2019 [cited by applicant]
US 20190276474A1 · Chan et al. · 2019 [cited by applicant]
US 20190374528A1 · Gray et al. · 2019 [cited by applicant]
US 20200010468A1 · Ji et al. · 2020 [cited by applicant]
US 20200347045A1 · Mainolfi et al. · 2020 [cited by applicant]
US 20200377469A1 · Mainolfi et al. · 2020 [cited by applicant]
US 20210002296A1 · Mainolfi et al. · 2021 [cited by applicant]
US 20210147382A1 · Bellenie et al. · 2021 [cited by applicant]
US 20210228562A1 · Weiss · 2021 [cited by applicant]
US 20210323952A1 · Mainolfi et al. · 2021 [cited by applicant]
US 20210395273A1 · Zheng et al. · 2021 [cited by applicant]
US 20230069104A1 · Mainolfi et al. · 2023 [cited by applicant]
US 20230089916A1 · Mainolfi et al. · 2023 [cited by applicant]
US 20230122219A1 · Weiss · 2023 [cited by examiner]
US 20230132715A1 · Ji et al. · 2023 [cited by applicant]
US 20230190940A1 · Zhang et al. · 2023 [cited by applicant]
US 20230219945A1 · Mainolfi et al. · 2023 [cited by applicant]
US 20230234953A1 · Weiss et al. · 2023 [cited by applicant]
US 20230241075A1 · Campbell et al. · 2023 [cited by applicant]
US 20230303526A1 · Mainolfi et al. · 2023 [cited by applicant]
US 20230405012A1 · Rong et al. · 2023 [cited by applicant]
US 20230406866A1 · Zheng · 2023 [cited by examiner]
US 20240059674A1 · Mainolfi et al. · 2024 [cited by applicant]
US 20240131016A1 · Weiss · 2024 [cited by applicant]
US 20240252656A1 · Hencken · 2024 [cited by applicant]
US 20240383887A1 · Weiss · 2024 [cited by applicant]
US 20250000985A1 · Mainolfi et al. · 2025 [cited by applicant]
US 20250082645A1 · Gollob et al. · 2025 [cited by applicant]
US 20250084105A1 · Leong et al. · 2025 [cited by applicant]
US 20250121073A1 · Mainolfi et al. · 2025 [cited by applicant]
US 20250163042A1 · Mainolfi et al. · 2025 [cited by applicant]
CN 105085620B · 2018 [cited by applicant]
WO WO1996007655A1 · 1996 [cited by applicant]
WO WO2001042246A2 · 2001 [cited by applicant]
WO WO2002020740A2 · 2002 [cited by applicant]
WO WO2002088112A1 · 2002 [cited by applicant]
WO WO2003063794A2 · 2003 [cited by applicant]
WO WO2004019973A1 · 2004 [cited by applicant]
WO WO2004089925A1 · 2004 [cited by applicant]
WO WO2004106328A1 · 2004 [cited by applicant]
WO WO2005007623A2 · 2005 [cited by applicant]
WO WO2005113554A2 · 2005 [cited by applicant]
WO WO2006029879A2 · 2006 [cited by applicant]
WO WO2006078846A1 · 2006 [cited by applicant]
WO WO2006105021A2 · 2006 [cited by applicant]
WO WO2006122806A2 · 2006 [cited by applicant]
WO WO2007005874A2 · 2007 [cited by applicant]
WO WO2007016176A2 · 2007 [cited by applicant]
WO WO2007044729A2 · 2007 [cited by applicant]
WO WO2007053452A1 · 2007 [cited by applicant]
WO WO2007070514A1 · 2007 [cited by applicant]
WO WO2007084786A1 · 2007 [cited by applicant]
WO WO2007129161A2 · 2007 [cited by applicant]
WO WO2008039218A2 · 2008 [cited by applicant]
WO WO2008109943A1 · 2008 [cited by applicant]
WO WO2008118802A1 · 2008 [cited by applicant]
WO WO2008132601A1 · 2008 [cited by applicant]
WO WO2009009116A2 · 2009 [cited by applicant]
WO WO2009044273A2 · 2009 [cited by applicant]
WO WO2009073620A2 · 2009 [cited by applicant]
WO WO2009114512A1 · 2009 [cited by applicant]
WO WO2009132238A2 · 2009 [cited by applicant]
WO WO2010019570A2 · 2010 [cited by applicant]
WO WO2010077634A1 · 2010 [cited by applicant]
WO WO2011028683A1 · 2011 [cited by applicant]
WO WO2011043371A1 · 2011 [cited by applicant]
WO WO2011056652A1 · 2011 [cited by applicant]
WO WO2011070024A1 · 2011 [cited by applicant]
WO WO2011090760A1 · 2011 [cited by applicant]
WO WO2011107553A1 · 2011 [cited by applicant]
WO WO2011109400A2 · 2011 [cited by applicant]
WO WO2011131407A1 · 2011 [cited by applicant]
WO WO2011140249A2 · 2011 [cited by applicant]
WO WO2012003281A2 · 2012 [cited by applicant]
WO WO2012007375A1 · 2012 [cited by applicant]
WO WO2012032433A1 · 2012 [cited by applicant]
WO WO2012068546A1 · 2012 [cited by applicant]
WO WO2012078559A2 · 2012 [cited by applicant]
WO WO2012084704A1 · 2012 [cited by applicant]
WO WO2012097013A1 · 2012 [cited by applicant]
WO WO2012129258A1 · 2012 [cited by applicant]
WO WO2012142237A1 · 2012 [cited by applicant]
WO WO2012145493A1 · 2012 [cited by applicant]
WO WO2013042137A1 · 2013 [cited by applicant]
WO WO2013066729A1 · 2013 [cited by applicant]
WO WO2013079174A1 · 2013 [cited by applicant]
WO WO2013087699A1 · 2013 [cited by applicant]
WO WO2013106535A1 · 2013 [cited by applicant]
WO WO2013106612A1 · 2013 [cited by applicant]
WO WO2013106614A1 · 2013 [cited by applicant]
WO WO2013106641A1 · 2013 [cited by applicant]
WO WO2013106643A2 · 2013 [cited by applicant]
WO WO2013106646A2 · 2013 [cited by applicant]
WO WO2013119716A1 · 2013 [cited by applicant]
WO WO2013132044A1 · 2013 [cited by applicant]
WO WO2013169264A1 · 2013 [cited by applicant]
WO WO2014008218A1 · 2014 [cited by applicant]
WO WO2014008992A1 · 2014 [cited by applicant]
WO WO2014011902A1 · 2014 [cited by applicant]
WO WO2014011906A2 · 2014 [cited by applicant]
WO WO2014011911A2 · 2014 [cited by applicant]
WO WO2014036357A1 · 2014 [cited by applicant]
WO WO2014044622A1 · 2014 [cited by applicant]
WO WO2014058685A1 · 2014 [cited by applicant]
WO WO2014058691A1 · 2014 [cited by applicant]
WO WO2014063061A1 · 2014 [cited by applicant]
WO WO2014074660A1 · 2014 [cited by applicant]
WO WO2014074675A1 · 2014 [cited by applicant]
WO WO2014108452A1 · 2014 [cited by applicant]
WO WO2014121931A1 · 2014 [cited by applicant]
WO WO2014121942A1 · 2014 [cited by applicant]
WO WO2014142237A1 · 2014 [cited by applicant]
WO WO2014143672A1 · 2014 [cited by applicant]
WO WO2015048281A1 · 2015 [cited by applicant]
WO WO2015068856A1 · 2015 [cited by applicant]
WO WO2015071393A1 · 2015 [cited by applicant]
WO WO2015091426A1 · 2015 [cited by applicant]
WO WO2015103453A1 · 2015 [cited by applicant]
WO WO2015104662A1 · 2015 [cited by applicant]
WO WO2015104688A1 · 2015 [cited by applicant]
WO WO2015150995A1 · 2015 [cited by applicant]
WO WO2015160845A2 · 2015 [cited by applicant]
WO WO2015164374A1 · 2015 [cited by applicant]
WO WO2015193846A1 · 2015 [cited by applicant]
WO WO2016011390A1 · 2016 [cited by applicant]
WO WO2016053769A1 · 2016 [cited by applicant]
WO WO2016053770A1 · 2016 [cited by applicant]
WO WO2016053771A1 · 2016 [cited by applicant]
WO WO2016053772A1 · 2016 [cited by applicant]
WO WO2016081679A1 · 2016 [cited by applicant]
WO WO2016105518A1 · 2016 [cited by applicant]
WO WO2016118666A1 · 2016 [cited by applicant]
WO WO2016144844A1 · 2016 [cited by applicant]
WO WO2016144846A1 · 2016 [cited by applicant]
WO WO2016144847A1 · 2016 [cited by applicant]
WO WO2016144848A1 · 2016 [cited by applicant]
WO WO2016144849A1 · 2016 [cited by applicant]
WO WO2016149668A1 · 2016 [cited by applicant]
WO WO2016169989A1 · 2016 [cited by applicant]
WO WO2016172560A1 · 2016 [cited by applicant]
WO WO2016174183A1 · 2016 [cited by applicant]
WO WO2016197032A1 · 2016 [cited by applicant]
WO WO2016197114A1 · 2016 [cited by applicant]
WO WO2016210034A1 · 2016 [cited by applicant]
WO WO2017004133A1 · 2017 [cited by applicant]
WO WO2017004134A1 · 2017 [cited by applicant]
WO WO2017007612A1 · 2017 [cited by applicant]
WO WO2017009798A1 · 2017 [cited by applicant]
WO WO2017009806A1 · 2017 [cited by applicant]
WO WO2017011371A1 · 2017 [cited by applicant]
WO WO2017011590A1 · 2017 [cited by applicant]
WO WO2017030814A1 · 2017 [cited by applicant]
WO WO2017033093A1 · 2017 [cited by applicant]
WO WO2017049068A1 · 2017 [cited by applicant]
WO WO2017059280A1 · 2017 [cited by applicant]
WO WO2017079267A1 · 2017 [cited by applicant]
WO WO2017108723A2 · 2017 [cited by applicant]
WO WO2017117473A1 · 2017 [cited by applicant]
WO WO2017117474A1 · 2017 [cited by applicant]
WO WO2017127430A1 · 2017 [cited by applicant]
WO WO2017161119A1 · 2017 [cited by applicant]
WO WO2017176708A1 · 2017 [cited by applicant]
WO WO2017176957A1 · 2017 [cited by applicant]
WO WO2017176958A1 · 2017 [cited by applicant]
WO WO2017197036A1 · 2017 [cited by applicant]
WO WO2017197046A1 · 2017 [cited by applicant]
WO WO2017197051A1 · 2017 [cited by applicant]
WO WO2017197055A1 · 2017 [cited by applicant]
WO WO2017197056A1 · 2017 [cited by applicant]
WO WO2017201449A1 · 2017 [cited by applicant]
WO WO2017205762A1 · 2017 [cited by applicant]
WO WO2017205766A1 · 2017 [cited by applicant]
WO WO2017207385A1 · 2017 [cited by applicant]
WO WO2017211924A1 · 2017 [cited by applicant]
WO WO2018052058A1 · 2018 [cited by applicant]
WO WO2018089736A1 · 2018 [cited by applicant]
WO WO2018098367A1 · 2018 [cited by applicant]
WO WO2018119441A1 · 2018 [cited by applicant]
WO WO2018144649A1 · 2018 [cited by applicant]
WO WO2018209012A1 · 2018 [cited by applicant]
WO WO2018237026A1 · 2018 [cited by applicant]
WO WO2019043214A1 · 2019 [cited by applicant]
WO WO2019060693A1 · 2019 [cited by applicant]
WO WO2019060742A1 · 2019 [cited by applicant]
WO WO2019084026A1 · 2019 [cited by applicant]
WO WO2019084030A1 · 2019 [cited by applicant]
WO WO2019099868A2 · 2019 [cited by applicant]
WO WO2019099926A1 · 2019 [cited by applicant]
WO WO2019133531A1 · 2019 [cited by applicant]
WO WO2019140380A1 · 2019 [cited by applicant]