IP Library › Granted Patent US 12,214,044
Granted Patent B2
US 12,214,044 · App. 18/165,774 · Granted Feb 4, 2025

Factor VIII zwitterionic polymer conjugates

Inventors: Stephen A. Charles (Ravenna, OH); Daniel Victor Perlroth (Palo Alto, CA); Li Song (Cupertino, CA); Martin Linsell (San Mateo, CA); Wayne To (San Mateo, CA); Didier Benoit (San Jose, CA); James Aggen (Westwood, MA)
Assignee: KODIAK SCIENCES INC.
A61K47/60A61K38/37A61K47/59A61K47/64C07K14/755C08F120/36C08G65/33324
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 12,214,044
App. No.
18/165,774
Granted
Feb 4, 2025
Kind
B2
Abstract

The present invention provides multi-armed high MW polymers containing hydrophilic groups conjugated to Factor VIII, and methods of preparing such polymers.

Claims (41)

1. A compound having the following formula:

wherein s is 1-20;

p is 1 to 12;

R2 is selected from the group consisting of alkyl, substituted alkyl, alkylene, alkoxy, carboxyalkyl, haloalkyl, cycloalkyl, cyclic alkyl ether, alkenyl, alkenylene, alkynyl, alkynylene, cycloalkylene, heterocycloalkyl, heterocycloalkylene, aryl, arylene, arylene-oxy, heteroaryl, amino, amido or any combination thereof; and

R3 is

 wherein R4, R5, and R6 are the same or different and are selected from the group consisting of:

 and

wherein Z is polymer, the polymer is synthesized with a monomer selected from the group consisting of:

 wherein

R7 is H or C 1 -6 alkyl, ZW is a zwitterion, and t is 1 to 6.

2. The compound of claim 1 , wherein R2 comprises a structure having the formula:

wherein m is an integer from 1 to 20.

3. The compound of claim 1 , wherein the zwitterion is phosphorylcholine.

4. The compound of claim 1 , wherein the monomer is 2-(methacryloyloxyethyl)-2′-(trimethylammoniumethyl) phosphate (MPC) or 2-(acryloyloxyethyl)-2′-(trimethylammoniumethyl) phosphate.

5. The compound of claim 4 , wherein the monomer is 2-(methacryloyloxyethyl)-2′-(trimethylammoniumethyl) phosphate (MPC).

6. The compound according to claim 1 , wherein the total molecular weight of the compound is about 500,000 to about 1,000,000 daltons.

7. The compound according to claim 6 , wherein the total molecular weight of the compound is about 650,000 to about 850,000 daltons.

8. The compound according to claim 7 , wherein the total molecular weight of the compound is about 750,000 daltons.

9. The compound of claim 1 , wherein R2 is

wherein X is 0 or an integer from 1 to 50, and Y is an integer from 1 to 50.

10. A method of synthesizing the compound of claim 1 , comprising coupling a functional agent

to an initiator having the structure R1-R2 R3) s , wherein:

s is 1-20;

R1 is —NH 2 ;

R2 is selected from the group consisting of alkyl, substituted alkyl, alkylene, alkoxy, carboxyalkyl, haloalkyl, cycloalkyl, cyclic alkyl ether, alkenyl, alkenylene, alkynyl, alkynylene, cycloalkylene, heterocycloalkyl, heterocycloalkylene, aryl, arylene, arylene-oxy, heteroaryl, amino, amido or any combination thereof; and

R3 is

 wherein R4, R5, and R6 are the same or different and are selected from the group consisting of:

 and

wherein Z is polymer, the polymer is synthesized with a monomer selected from the group consisting of:

 wherein R7 is H or C 1-6 alkyl, ZW is a zwitterion, and t is 1 to 6;

R8 is

 and

R9 is

wherein p is 1 to 12.

11. The method of claim 10 , wherein R2 comprises a structure having the formula:

wherein m is an integer from 1 to 20.

12. The method of claim 10 , wherein the zwitterion is phosphorylcholine.

13. The method of claim 10 , wherein the monomer is 2-(methacryloyloxyethyl)-2′-(trimethylammoniumethyl) phosphate (MPC) or 2-(acryloyloxyethyl)-2′-(trimethylammoniumethyl) phosphate.

14. The method of claim 13 , wherein the monomer is 2-(methacryloyloxyethyl)-2′-(trimethylammoniumethyl) phosphate (MPC).

15. The method of claim 10 , wherein R2 is

wherein X is 0 or an integer from 1 to 50, and Y is an integer from 1 to 50.

Assignments (3)
CHANGE OF NAME Recorded Jul 30, 2025
From: OLIGASIS, LLC
To: KODIAK SCIENCES INC.
Reel/Frame 072315/0791 →
EMPLOYEE AGREEMENT Recorded Dec 11, 2024
From: CHARLES, STEPHEN A.; SONG, LI; LINSELL, MARTIN S.; TO, WAYNE; AGGEN, JAMES
To: OLIGASIS, LLC
Reel/Frame 071809/0599 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 4, 2024
From: PERLROTH, D. VICTOR; BENOIT, DIDIER
To: KODIAK SCIENCES INC.
Reel/Frame 069585/0136 →
Continuity (4)
Continuation 16781869 · Feb 4, 2020
Continuation 14916180
Provisional Application 61875099 · Sep 8, 2013
Related Publication 20230173081A1 · Jun 8, 2023
References Cited (400)
US 4634664A · Oestberg · 1987 [cited by applicant]
US 4634666A · Engleman et al. · 1987 [cited by applicant]
US 4757006A · Toole, Jr. et al. · 1988 [cited by applicant]
US 4868112A · Toole, Jr. · 1989 [cited by applicant]
US 4892538A · Aebischer et al. · 1990 [cited by applicant]
US 5198349A · Kaufman · 1993 [cited by applicant]
US 5225539A · Winter · 1993 [cited by applicant]
US 5250421A · Kaufman et al. · 1993 [cited by applicant]
US 5283187A · Aebischer et al. · 1994 [cited by applicant]
US 5336603A · Capon et al. · 1994 [cited by applicant]
US 5530101A · Queen et al. · 1996 [cited by applicant]
US 5545806A · Lonberg et al. · 1996 [cited by applicant]
US 5565332A · Hoogenboom et al. · 1996 [cited by applicant]
US 5569825A · Lonberg et al. · 1996 [cited by applicant]
US 5585089A · Queen et al. · 1996 [cited by applicant]
US 5625126A · Lonberg et al. · 1997 [cited by applicant]
US 5633425A · Lonberg et al. · 1997 [cited by applicant]
US 5661016A · Lonberg et al. · 1997 [cited by applicant]
US 5663425A · Detroit et al. · 1997 [cited by applicant]
US 5681746A · Bodner et al. · 1997 [cited by applicant]
US 5733743A · Johnson et al. · 1998 [cited by applicant]
US 5733873A · Osterberg et al. · 1998 [cited by applicant]
US 5741923A · Driver et al. · 1998 [cited by applicant]
US 5763548A · Matyjaszewski et al. · 1998 [cited by applicant]
US 5770429A · Lonberg et al. · 1998 [cited by applicant]
US 5789487A · Matyjaszewski et al. · 1998 [cited by applicant]
US 5789650A · Lonberg et al. · 1998 [cited by applicant]
US 5807937A · Matyjaszewski et al. · 1998 [cited by applicant]
US 5814318A · Lonberg et al. · 1998 [cited by applicant]
US 5834597A · Tso et al. · 1998 [cited by applicant]
US 5837242A · Holliger et al. · 1998 [cited by applicant]
US 5858657A · Winter et al. · 1999 [cited by applicant]
US 5859205A · Adair et al. · 1999 [cited by applicant]
US 5871907A · Winter et al. · 1999 [cited by applicant]
US 5872218A · Wolf et al. · 1999 [cited by applicant]
US 5874299A · Lonberg et al. · 1999 [cited by applicant]
US 5877218A · Herzig et al. · 1999 [cited by applicant]
US 5877397A · Lonberg et al. · 1999 [cited by applicant]
US 5882644A · Chang et al. · 1999 [cited by applicant]
US 5919766A · Osterberg et al. · 1999 [cited by applicant]
US 5945491A · Matyjaszewski et al. · 1999 [cited by applicant]
US 5981786A · Kitano et al. · 1999 [cited by applicant]
US 6111022A · Matyjaszewski et al. · 2000 [cited by applicant]
US 6121371A · Matyjaszewski et al. · 2000 [cited by applicant]
US 6124411A · Matyjaszewski et al. · 2000 [cited by applicant]
US 6162882A · Matyjaszewski et al. · 2000 [cited by applicant]
US 6348554B1 · Roos et al. · 2002 [cited by applicant]
US 6407187B1 · Matyjaszewski et al. · 2002 [cited by applicant]
US 6407213B1 · Carter et al. · 2002 [cited by applicant]
US 6512060B1 · Matyjaszewski et al. · 2003 [cited by applicant]
US 6538091B1 · Matyjaszewski et al. · 2003 [cited by applicant]
US 6541580B1 · Matyjaszewski et al. · 2003 [cited by applicant]
US 6555593B1 · Hoyle et al. · 2003 [cited by applicant]
US 6583272B1 · Bailon · 2003 [cited by applicant]
US 6624262B2 · Matyjaszewski et al. · 2003 [cited by applicant]
US 6627314B2 · Matyjaszewski et al. · 2003 [cited by applicant]
US 6657043B1 · Guerret et al. · 2003 [cited by applicant]
US 6759491B2 · Matyjaszewski et al. · 2004 [cited by applicant]
US 6780428B2 · Ranger et al. · 2004 [cited by applicant]
US 6790919B2 · Matyjaszewski et al. · 2004 [cited by applicant]
US 6852816B2 · Lewis et al. · 2005 [cited by applicant]
US 6881557B2 · Foote · 2005 [cited by applicant]
US 6887962B2 · Matyjaszewski et al. · 2005 [cited by applicant]
US 6979556B2 · Simmons et al. · 2005 [cited by applicant]
US 7019082B2 · Matyjaszewski et al. · 2006 [cited by applicant]
US 7049373B2 · Matyjaszewski et al. · 2006 [cited by applicant]
US 7056455B2 · Matyjaszewski et al. · 2006 [cited by applicant]
US 7060271B2 · Ramakrishnan et al. · 2006 [cited by applicant]
US 7064166B2 · Matyjaszewski et al. · 2006 [cited by applicant]
US 7125938B2 · Matyjaszewski et al. · 2006 [cited by applicant]
US 7157530B2 · Matyjaszewski et al. · 2007 [cited by applicant]
US 7169901B2 · Baca et al. · 2007 [cited by applicant]
US 7200990B2 · Lewis et al. · 2007 [cited by applicant]
US 7300990B2 · Lewis et al. · 2007 [cited by applicant]
US 7306799B2 · Wiegand et al. · 2007 [cited by applicant]
US 7348424B2 · Miyazawa et al. · 2008 [cited by applicant]
US 7374757B2 · Papadopoulos et al. · 2008 [cited by applicant]
US 7375193B2 · Baca et al. · 2008 [cited by applicant]
US 7521541B2 · Eigenbrot et al. · 2009 [cited by applicant]
US 7569655B2 · Pacetti et al. · 2009 [cited by applicant]
US 7740850B2 · Zhu et al. · 2010 [cited by applicant]
US 7754208B2 · Ledbetter et al. · 2010 [cited by applicant]
US 7754855B1 · Cox, III et al. · 2010 [cited by applicant]
US 7759472B2 · Shima et al. · 2010 [cited by applicant]
US 7855178B2 · Alitalo et al. · 2010 [cited by applicant]
US 7893173B2 · Matyjaszewski et al. · 2011 [cited by applicant]
US 8003097B2 · Schroeter et al. · 2011 [cited by applicant]
US 8008453B2 · Gegg et al. · 2011 [cited by applicant]
US 8187597B2 · Shima et al. · 2012 [cited by applicant]
US 8206707B2 · Shima et al. · 2012 [cited by applicant]
US 8273353B2 · Davis-Smyth et al. · 2012 [cited by applicant]
US 8455622B2 · McDonagh et al. · 2013 [cited by applicant]
US 8486397B2 · Bagri et al. · 2013 [cited by applicant]
US 8492527B2 · Fuh et al. · 2013 [cited by applicant]
US 8512699B2 · Fuh et al. · 2013 [cited by applicant]
US 8765432B2 · Charles · 2014 [cited by applicant]
US 8815236B2 · Burke et al. · 2014 [cited by applicant]
US 8846021B2 · Charles · 2014 [cited by applicant]
US 9079953B2 · Harding et al. · 2015 [cited by applicant]
US 9416210B2 · Emrick et al. · 2016 [cited by applicant]
US 9840553B2 · Perlroth et al. · 2017 [cited by applicant]
US 10363290B2 · Perlroth et al. · 2019 [cited by applicant]
US 10702608B2 · Charles et al. · 2020 [cited by applicant]
US 11066465B2 · Perlroth et al. · 2021 [cited by applicant]
US 11071771B2 · Perlroth et al. · 2021 [cited by applicant]
US 11155610B2 · Perlroth et al. · 2021 [cited by applicant]
US 11584790B2 · Perlroth et al. · 2023 [cited by applicant]
US 11590235B2 · Charles et al. · 2023 [cited by applicant]
US 11819531B2 · Charles et al. · 2023 [cited by applicant]
US 11912784B2 · Ehrlich et al. · 2024 [cited by applicant]
US 12071476B2 · Jacobson et al. · 2024 [cited by applicant]
US 20030143596A1 · Bentley et al. · 2003 [cited by applicant]
US 20030204022A1 · Kennedy et al. · 2003 [cited by applicant]
US 20040063881A1 · Lewis et al. · 2004 [cited by applicant]
US 20040253596A1 · Pawlak et al. · 2004 [cited by applicant]
US 20050009988A1 · Harris et al. · 2005 [cited by applicant]
US 20050112088A1 · Zhao et al. · 2005 [cited by applicant]
US 20050118651A1 · Basi et al. · 2005 [cited by applicant]
US 20050123501A1 · Lews · 2005 [cited by applicant]
US 20050136049A1 · Ledbetter et al. · 2005 [cited by applicant]
US 20050159556A1 · Lewis et al. · 2005 [cited by applicant]
US 20050180945A1 · Chaikof et al. · 2005 [cited by applicant]
US 20050220880A1 · Lewis et al. · 2005 [cited by applicant]
US 20050276796A1 · Tomatsu et al. · 2005 [cited by applicant]
US 20060069203A1 · Lewis et al. · 2006 [cited by applicant]
US 20060135714A1 · Lewis et al. · 2006 [cited by applicant]
US 20060165804A1 · Lewis et al. · 2006 [cited by applicant]
US 20060167230A1 · Koga et al. · 2006 [cited by applicant]
US 20060217285A1 · Destarac · 2006 [cited by applicant]
US 20060234347A1 · Harding et al. · 2006 [cited by applicant]
US 20060234437A1 · Harding et al. · 2006 [cited by applicant]
US 20070041967A1 · Jung et al. · 2007 [cited by applicant]
US 20070111279A1 · Rosenberg · 2007 [cited by applicant]
US 20070141104A1 · Hauenstein · 2007 [cited by applicant]
US 20080008736A1 · Glauser · 2008 [cited by applicant]
US 20080124450A1 · Pacetti · 2008 [cited by applicant]
US 20080147175A1 · Pacetti et al. · 2008 [cited by applicant]
US 20080147178A1 · Pacetti et al. · 2008 [cited by applicant]
US 20080199464A1 · Plowman et al. · 2008 [cited by applicant]
US 20090060906A1 · Barry et al. · 2009 [cited by applicant]
US 20090061533A1 · Minami · 2009 [cited by applicant]
US 20090117103A1 · Devalaraja et al. · 2009 [cited by applicant]
US 20090324679A1 · Ippoliti et al. · 2009 [cited by applicant]
US 20100111942A1 · Shima et al. · 2010 [cited by applicant]
US 20100158850A1 · Baker, Jr. et al. · 2010 [cited by applicant]
US 20100166700A1 · Charles · 2010 [cited by applicant]
US 20110033378A1 · Dimasi et al. · 2011 [cited by applicant]
US 20110069176A1 · Lin et al. · 2011 [cited by applicant]
US 20110165648A1 · Campange et al. · 2011 [cited by applicant]
US 20110213105A1 · Jakubowski et al. · 2011 [cited by applicant]
US 20120100136A1 · Patel et al. · 2012 [cited by applicant]
US 20120213705A1 · Dimasi et al. · 2012 [cited by applicant]
US 20120282211A1 · Washburn et al. · 2012 [cited by applicant]
US 20120322738A1 · Behrens et al. · 2012 [cited by applicant]
US 20130040889A1 · Bolt et al. · 2013 [cited by applicant]
US 20130045522A1 · Charles et al. · 2013 [cited by applicant]
US 20130071394A1 · Troyer et al. · 2013 [cited by applicant]
US 20130259881A1 · Fandl et al. · 2013 [cited by applicant]
US 20130334517A1 · Hong et al. · 2013 [cited by applicant]
US 20140024776A1 · Charles et al. · 2014 [cited by applicant]
US 20140170140A1 · Bennett et al. · 2014 [cited by applicant]
US 20140242082A1 · Shima et al. · 2014 [cited by applicant]
US 20150004128A1 · Charles et al. · 2015 [cited by applicant]
US 20150050714A1 · Charles · 2015 [cited by applicant]
US 20150071861A1 · Kondo et al. · 2015 [cited by applicant]
US 20150093390A1 · Bansal · 2015 [cited by applicant]
US 20150158952A1 · Mao et al. · 2015 [cited by applicant]
US 20160008485A1 · Marquette et al. · 2016 [cited by applicant]
US 20160346400A1 · Emrick et al. · 2016 [cited by applicant]
US 20160369005A1 · Lippincott et al. · 2016 [cited by applicant]
US 20170007710A1 · Charles et al. · 2017 [cited by applicant]
US 20170143841A1 · Charles et al. · 2017 [cited by applicant]
US 20190270806A1 · Jacobson et al. · 2019 [cited by applicant]
US 20200000930A1 · Charles · 2020 [cited by applicant]
US 20200171179A1 · Charles et al. · 2020 [cited by applicant]
US 20200262905A1 · Perlroth et al. · 2020 [cited by applicant]
US 20210107999A1 · Ehrlich et al. · 2021 [cited by applicant]
US 20210324063A1 · Perlroth et al. · 2021 [cited by applicant]
US 20210402015A1 · Charles et al. · 2021 [cited by applicant]
US 20220096643A1 · Charles · 2022 [cited by applicant]
US 20230250133A1 · Zurbriggen et al. · 2023 [cited by applicant]
US 20230277616A9 · Charles et al. · 2023 [cited by applicant]
US 20230382983A1 · Perlroth et al. · 2023 [cited by applicant]
US 20240084043A1 · Ehrlich et al. · 2024 [cited by applicant]
US 20240197810A1 · Charles et al. · 2024 [cited by applicant]
US 20240209076A1 · Perlroth et al. · 2024 [cited by applicant]
US 20240238427A1 · Ehrlich et al. · 2024 [cited by applicant]
US 20240293585A1 · Charles et al. · 2024 [cited by applicant]
AU 2015207898 · 2015 [cited by applicant]
AU 2017201930 · 2017 [cited by applicant]
CN 1486995 · 2004 [cited by applicant]
CN 101053681 · 2007 [cited by applicant]
CN 101389690 · 2009 [cited by applicant]
CN 101575402 · 2009 [cited by applicant]
CN 102811713 · 2012 [cited by applicant]
CN 103193819 · 2013 [cited by applicant]
CN 103421039 · 2013 [cited by applicant]
CN 103492489 · 2014 [cited by applicant]
CN 106075466 · 2016 [cited by applicant]
CN 106432557 · 2017 [cited by applicant]
CN 107428824 · 2017 [cited by applicant]
CN 108712911 · 2018 [cited by applicant]
CO 12119310 · 2012 [cited by applicant]
CO 12203725 · 2013 [cited by applicant]
EP 0306968 · 1993 [cited by applicant]
EP 1465933 · 2007 [cited by applicant]
EP 1592719 · 2008 [cited by applicant]
EP 1988910 · 2008 [cited by applicant]
EP 1732621 · 2009 [cited by applicant]
EP 2260873 · 2010 [cited by applicant]
EP 2363414 · 2011 [cited by applicant]
EP 2512462 · 2012 [cited by applicant]
EP 2203180 · 2012 [cited by applicant]
EP 3222142 · 2017 [cited by applicant]
EP 3254678 · 2017 [cited by applicant]
EP 3041513 · 2020 [cited by applicant]
JP H09504299 · 1997 [cited by applicant]
JP H10139832 · 1998 [cited by applicant]
JP H11217588 · 1999 [cited by applicant]
JP 2000093169 · 2000 [cited by applicant]
JP 2002512265 · 2002 [cited by applicant]
JP 2003064132 · 2003 [cited by applicant]
JP 2003104913 · 2003 [cited by applicant]
JP 2005239989 · 2005 [cited by applicant]
JP 2005255969 · 2005 [cited by applicant]
JP 2006503549 · 2006 [cited by applicant]
JP 2007516302 · 2007 [cited by applicant]
JP 2007263935 · 2007 [cited by applicant]
JP 2007314736 · 2007 [cited by applicant]
JP 2008133434 · 2008 [cited by applicant]
JP 2008524247 · 2008 [cited by applicant]
JP 2008239997 · 2008 [cited by applicant]
JP 2008297488 · 2008 [cited by applicant]
JP 2009042617 · 2009 [cited by applicant]
JP 2009114283 · 2009 [cited by applicant]
JP 2009532330 · 2009 [cited by applicant]
JP 2009533519 · 2009 [cited by applicant]
JP 2009274998 · 2009 [cited by applicant]
JP 2009542862 · 2009 [cited by applicant]
JP 2009543895 · 2009 [cited by applicant]
JP 2010013651 · 2010 [cited by applicant]
JP 2010117189 · 2010 [cited by applicant]
JP 2012025820 · 2012 [cited by applicant]
JP 2013515099 · 2013 [cited by applicant]
JP 2013534931 · 2013 [cited by applicant]
JP 2014043453 · 2014 [cited by applicant]
JP 2014043456 · 2014 [cited by applicant]
JP 5745009 · 2015 [cited by applicant]
JP 5760007 · 2015 [cited by applicant]
JP 201614015 · 2016 [cited by applicant]
JP 5846044 · 2016 [cited by applicant]
JP 2016040371 · 2016 [cited by applicant]
JP 2016530302 · 2016 [cited by applicant]
JP 2017031410 · 2017 [cited by applicant]
JP 2018087330 · 2018 [cited by applicant]
JP 2019081765 · 2019 [cited by applicant]
JP 2020183404 · 2021 [cited by applicant]
KR 100808116 · 2008 [cited by applicant]
KR 20120123340 · 2012 [cited by applicant]
KR 20130097636 · 2013 [cited by applicant]
KR 101852044 · 2018 [cited by applicant]
MX 2012006970 · 2012 [cited by applicant]
MX 2012011876 · 2012 [cited by applicant]
MX 346423 · 2017 [cited by applicant]
MX 2016017290 · 2017 [cited by applicant]
WO WO9110741 · 1991 [cited by applicant]
WO WO9117271 · 1991 [cited by applicant]
WO WO9201047 · 1992 [cited by applicant]
WO WO9301221 · 1993 [cited by applicant]
WO WO9312227 · 1993 [cited by applicant]
WO WO9325673 · 1993 [cited by applicant]
WO WO9416748 · 1994 [cited by applicant]
WO WO9714702 · 1997 [cited by applicant]
WO WO9714703 · 1997 [cited by applicant]
WO WO9845331 · 1998 [cited by applicant]
WO WO0059968 · 2000 [cited by applicant]
WO WO0118080 · 2001 [cited by applicant]
WO WO0141827 · 2001 [cited by applicant]
WO WO02028929 · 2002 [cited by applicant]
WO WO03062290 · 2003 [cited by applicant]
WO WO03074026 · 2003 [cited by applicant]
WO WO03074090 · 2003 [cited by applicant]
WO WO2004020405 · 2004 [cited by applicant]
WO WO2004063237 · 2004 [cited by applicant]
WO WO2004091494 · 2004 [cited by applicant]
WO WO2004113394 · 2004 [cited by applicant]
WO WO2005028539 · 2005 [cited by applicant]
WO WO2005058367 · 2005 [cited by applicant]
WO WO2005117984 · 2005 [cited by applicant]
WO WO2006063055 · 2006 [cited by applicant]
WO WO2006118547 · 2006 [cited by applicant]
WO WO2007005253 · 2007 [cited by applicant]
WO WO2007075534 · 2007 [cited by applicant]
WO WO2007100902 · 2007 [cited by applicant]
WO WO2007100905 · 2007 [cited by applicant]
WO WO2007148230 · 2007 [cited by applicant]
WO WO2008003099 · 2008 [cited by applicant]
WO WO2008020827 · 2008 [cited by applicant]
WO WO2008025856 · 2008 [cited by applicant]
WO WO2008098930 · 2008 [cited by applicant]
WO WO2008112257 · 2008 [cited by applicant]
WO WO2008112289 · 2008 [cited by applicant]
WO WO2008144248 · 2008 [cited by applicant]
WO WO2008155134 · 2008 [cited by applicant]
WO WO2009052249 · 2009 [cited by applicant]
WO WO2005047334 · 2009 [cited by applicant]
WO WO2009066746 · 2009 [cited by applicant]
WO WO2009138473 · 2009 [cited by applicant]
WO WO2010040508 · 2010 [cited by applicant]
WO WO2010068862 · 2010 [cited by applicant]
WO WO2010068864 · 2010 [cited by applicant]
WO WO2010111625 · 2010 [cited by applicant]
WO WO2011075185 · 2011 [cited by applicant]
WO WO2011075736 · 2011 [cited by applicant]
WO WO2011130694 · 2011 [cited by applicant]
WO WO2013059137 · 2013 [cited by applicant]
WO WO2013093809 · 2013 [cited by applicant]
WO WO2014060401 · 2014 [cited by applicant]
WO WO2014160507 · 2014 [cited by applicant]
WO WO2015035342 · 2015 [cited by applicant]
WO WO2015200905 · 2015 [cited by applicant]
WO WO2017117464 · 2017 [cited by applicant]
WO WO2018191548 · 2018 [cited by applicant]
Office Action for European Application No. EP 20188750.2 in 4 pages, dated Dec. 11, 2023. [cited by applicant]
Office Action for Japanese Application No. JP 2022-184617 with English translation in 10 pages, dated Nov. 7, 2023. [cited by applicant]
Office Action for Japanese Application No. JP 2022-184617 with English translation in 6 pages, dated Sep. 3, 2024. [cited by applicant]
“Facts About Diabetic Eye Disease”, National Eye Institute, https://nei.nih.gov/health/diabetic/retinopathy, publication reviewed Sep. 2015, accessed Mar. 27, 2018, in 7 pages. The reference is a webpage, Applicants not… [cited by applicant]
“Papain”, MilliporeSigma, webpage accessed Aug. 10, 2021 [publication of information on webpage unknown], in 4 pages. URL: https://www.sigmaaldrich.com/US/en/technical-documents/technical-article/research-and-disease-ar… [cited by applicant]
Ambati et al., “Mechanisms of age-related macular degeneration,” Neuron, vol. 75, No. 1, pp. 26-39, 2012. [cited by applicant]
Anderson, W.F., “Human gene therapy,” Science, May 8, 1992, vol. 256, No. 5058, pp. 808-813. [cited by applicant]
Andrae et al., “Role of platelet-derived growth factors in physiology and medicine,” Genes & Development, vol. 22, pp. 1276-1312, 2008. [cited by applicant]
Armulik, A. et al., “Endothelial/Pericyte Interactions,” Circulation Research, vol. 97, Issue 6, pp. 512-523, Sep. 16, 2005. [cited by applicant]
Baluk, P. et al., “Cellular abnormalities of blood vessels as targets in cancer,” Current Opinion in Genetics & Development, vol. 15, Issue 1, pp. 102-111, Feb. 2005. [cited by applicant]
Bates, D.O. et al., “Vascular endothelial growth factor increases microvascular permeability via a Ca(2+)-dependent pathway,” American Journal of Physiology, vol. 273, No. 2, pp. H687-H694, Aug. 1, 1997. [cited by applicant]
Berthold, W. et al., “Protein Purification: Aspects of Processes for Pharmaceutical Products,” Biologicals, vol. 22, Issue 2, pp. 135-150, Jun. 1994. [cited by applicant]
Blong, M. Renee et al., “Tetramerization domain of human butyrylcholinesterase is at the C-terminus,” Biochemical Journal, vol. 327, No. 3, pp. 747-757, Nov. 1, 1997. [cited by applicant]
Bontempo, et al., “Cysteine-Reactive Polymers Synthesized by Atom Transfer Radical Polymerization for Conjugation to Proteins,” J. Am. Chem. Soc. (2004), 126, pp. 15372-15373. [cited by applicant]
Bowen-Pope et al., “History of Discovery: Platelet-derived Growth Factor,” Arterioscler Thromb Vasc Biol., vol. 31, No. 11, pp. 2397-2401, Nov. 2011. [cited by applicant]
Brown, D. et al., “Ranibizumab versus Verteporfin for Neovascular Age-Related Macular Degeneration,” The New England Journal of Medicine, vol. 355, No. 14, pp. 1432-1444, Oct. 5, 2006. [cited by applicant]
Cai, Y. et al., “Direct Synthesis and Stimulus-Responsive Micellization of Y-Shaped Hydrophilic Block Copolymers”, Macromolecules, vol. 37, No. 26, Dec. 2004, pp. 9728-9737. DOI: 10.1021/ma0487756. [cited by applicant]
Capon, D. et al., “Designing CD4 immunoadhesins for AIDS therapy,” Nature, 1989, vol. 337, pp. 525-531. [cited by applicant]
Carmeliet, “Mechanisms of angiogenesis and arteriogenesis,” Nature Medicine, vol. 6, No. 3, pp. 389-395, 2000. [cited by applicant]
Carmeliet, P., “Angiogenesis in health and disease,” Nature Medicine, vol. 9, pp. 653-660, (2003). [cited by applicant]
Carmeliet, P., “Synergism between vascular endothelial growth factor and placental growth factor contributes to angiogenesis and plasma extravasation in pathological conditions,” Nature Medicine, vol. 7, No. 5, pp. 575-… [cited by applicant]
Casset, F. et al. A Peptide Mimetic of an Anti0CD4 Monoclonal Antibody by Rational Design, Biochemical and Biophysical Research Communications, vol. 307, pp. 198-205, (2003). [cited by applicant]
Chakravarthy, R. et al., “Efficacy of extrinsic stain removal by novel dentifrice containing papain and bromelain extracts”, J. Young Pharm, 2012, vol. 4(4), pp. 245-249. [cited by applicant]
Chandler, W. et al., “Comparison of Three Methods for Measuring Factor VIII Levels in Plasma”, American Journal of Clinical Pathology, Jul. 2003, vol. 120, pp. 34-39. [cited by applicant]
Chen et al., “Factors affecting endotoxin removal from recombinant therapeutic proteins by anion exchange chromatography,” Protein Expression and Purification, vol. 64, pp. 76-81, 2009. [cited by applicant]
Chen, et al., “Lubrication at Physiological Pressures by Polyzwitterionic Brushes,” Science, (2009), 323, pp. 1698-1701. [cited by applicant]
Chen, et al., “Polymeric Phosphorylcholine-Camptothecin Conjugates Prepared by Controlled Free Radical Polymerization and Click Chemistry,” Bioconjugate Chem., Nov. 2009, vol. 20(12), pp. 2331-2341. [cited by applicant]
Chen, Y et al. “Selection and Analysis an Optimized Anti-VEGF Antibody: Crystal Structure of an Affinity-Matured Complex with Antigen”, J. Mol. Biol,, vol. 293, pp. 865-881 (1999). [cited by applicant]
Chothia, C. et al., “Canonical structures for the hypervariable regions of immunoglobulins,” Journal of Molecular Biology, Aug. 20, 1987, vol. 196, Issue 4, pp. 901-917. [cited by applicant]
Chothia, C. et al., “Conformations of immunoglobulin hypervariable regions,” Nature, Dec. 1989, vol. 342, pp. 877-883. [cited by applicant]
Christy, N.E. et al., “Antibiotic prophylaxis of postoperative endophthalmitis,” Annals of Ophthalmology, vol. 11, No. 8, pp. 1261-1265, Aug. 1, 1979. [cited by applicant]
Cohen, S.Y. et al., “Causes of unsuccessful ranibizumab treatment in exudative age-related macular degeneration in clinical settings,” Retina, vol. 32, Issue 8, pp. 1480-1485, Sep. 2012. [cited by applicant]
Crowe, et al., “Recombinant human respiratory syncytial virus (RSV) monoclonal antibody Fab is effective therapeutically when introduced directly into the lungs of RSV-infected mice,” Proc. Natl. Acad. Sci. USA, (1994) … [cited by applicant]
Curriculum Vitae of Didier G. Benoit, filed in U.S. Appl. No. 12/281,071, filed Feb. 4, 2013, in 6 pages. [cited by applicant]
Da Pieve, et al., “Conjugation of PolyPEG®, Linear PEG and Branched PEG to a Thiol-Modified Aptamer,” Poster, Warwick Effect Polymers Ltd, retrieved from <http:www.wep-ltd.co.uk> (2010). [cited by applicant]
Da Pieve, et al., “Modification of Thiol Functionalized Aptamers by Conjugation of Synthetic Polymers,” Bioconjugate Chem., (2010), 21:1, pp. 169-174. [cited by applicant]
Daneshian, M. et al., “In vitro pyrogen test for toxic or immunomodulatory drugs,” Journal of Immunological Methods, vol. 313, Issues 1-2, pp. 169-175, Jun. 30, 2006. [cited by applicant]
Database WPI Week 200833 Thomson Scientific, London, GB; AN 2008-E72441 XP002795732, & CN 101 053 681 A (Univ Tianjin), Oct. 17, 2007. [cited by applicant]
De Pascalis, R. et al., “Grafting of ‘abbreviated’ complementarity-determining regions containing specificity-determining residues essential for ligand contact to engineer a less immunogenic humanized monoclonal antibod… [cited by applicant]
Declaration of Didier G. Benoit, filed in U.S. Appl. No. 12/281,071, filed Feb. 5, 2013 (signed Jan. 31, 2013), in 8 pages. [cited by applicant]
Declaration of Harvey N. Masonson, M.D., under 37 C.F.R., for U.S. Appl. No. 12/465,051, filed May 13, 2009, including Exhibits A, B, and C, signed Jul. 6, 2011, in 50 pages. [cited by applicant]
Declaration of Stephen A. Charles under 37 CFR 1.132 filed in U.S. Appl. No. 13/959,563, dated Dec. 6, 2013, in 20 pages. [cited by applicant]
Dillon et al., “Structural and functional characterization of disulfide isoforms of the human IgG2 subclass,” The Journal of Biological Chemistry, vol. 283, No. 23, pp. 16206-16215, 2008. [cited by applicant]
Ding, J.L. et al., “A new era of pyrogen testing,” Trends in Biotechnology, vol. 19, Issue 8, pp. 277-281, Aug. 1, 2001. [cited by applicant]
Dong, et al., “ARGET ATRP of 2-(Dimethylamino)ethyl Methacrylate as an Intrinsic Reducing Agent,” Macromolecules, (2008), 41:19 pp. 6868-6870. [cited by applicant]
Dong, et al., “Well-Defined High-Molecular-Weight Polyacrylonitrile via Activators Regenerated by Electron Transfer ATRP,” Macromolecules, (2007), 40:9, pp. 2974-2977. [cited by applicant]
Du et al. “pH-Sensitive Vesicles based on a Biocompatible Zwitterionic Diblock Copolymer” J. Am. Chem. Soc., Dec. 1, 2005, 127, 17982-17983. [cited by applicant]
Edelman et al., “The covalent structure of an entire yG immunoglobulin molecule,” Proceedings of the National Academy of Sciences, vol. 63, pp. 78-85, May 1, 1969. [cited by applicant]
Engelgau, M et al. Evolving Diabetes Burden in the United States. Ann of Int Med. 140 (11): 945-951, 2004. [cited by applicant]
Exhibit D filed in U.S. Appl. No. 12/281,071, filed Feb. 4, 2013, in 1 page. [cited by applicant]
Exhibit E filed in U.S. Appl. No. 12/281,071, filed Feb. 4, 2013, in 1 page. [cited by applicant]
Fares, F.A. et al., “Design of a long-acting follitropin agonist by fusing the C-terminal sequence of the chorionic gonadotropin beta subunit to the follitropin beta subunit,” Proc Natl Acad Sci USA, vol. 89, No. 10, pp… [cited by applicant]
Ferrara, et al. “Development of Ranibizumab, An Anti-Vascular Endothelial Growth Factor Antigen Binding Fragment, as Therapy for Neovascular Age-Related Macular Degeneration”, Retina, The Journal of Retinal and Vitreous… [cited by applicant]
Ferrara, et al., “The Biology of VEGF and its Receptors”, Nature Medicine, vol. 9 No. 6, pp. 669-676, (2003). [cited by applicant]
Ferrara, N. et al., “The Biology of Vascular Endothelial Growth Factor,” Endocrine Reviews, vol. 18, No. 1, pp. 4-25, (1997). [cited by applicant]
Fiske, M. et al., “Method for reducing endotoxin in Moraxella catarrhalis UspA2 protein preparations,” Journal of Chromatography B: Biomedical Sciences and Applications, vol. 753, Issue 2, pp. 269-278, Apr. 5, 2001. [cited by applicant]
Folkman, J., “Angiogenesis: an organizing principle for drug discover?” Nature Reviews, Drug Discovery, vol. 6, pp. 273-286, Apr. 2007. [cited by applicant]
Fontaine et al., “Long-Term Stabilization of Maleimide-Thiol Conjugates,” Bioconjugate Chem., vol. 26, pp. 145-152, 2015. [cited by applicant]
Foster, Graham R., “Pegylated interferons for the treatment of chronic Hepatitis C,” Drugs, vol. 70, Issue 2, pp. 147-165, Jan. 2010. [cited by applicant]
Friedman, D.S. et al., “Prevalence of age-related macular degeneration in the United States,” Arch. Ophthalmol., vol. 122, No. 4, pp. 564-572, Apr. 2004. [cited by applicant]
Geng, J. et al. Site-Directed Conjugation of “Clicked” Glycopolymers to Form Glycoprotein Mimics: Binding to Mammalian Lectin and Induction of Immunological Function, J. Am. Chem. Soc., 2007, 129, pp. 15156-15163. [cited by applicant]
Gillies, E. R. et al., “Dendrimers and Dendritic Polymers in Drug Delivery,” Drug Delivery today, Jan. 2005, vol. 10, No. 1, pp. 35-43. [cited by applicant]
Greene, T. W. et al., “Protective Groups in Organic Synthesis,” 3rd Edition, John Wiley and Sons, Inc., New York, (1999). In 52 pages which includes only the Title Page and Table of Contents. [cited by applicant]
Haddleton, et al., “Phenolic Ester-Based Initiators for Transition Metal Mediated Living Polymerization,” Macromolecules, (1999), 32, pp. 8732-8739. [cited by applicant]
Haishima, Y et al. Estimation of uncertainty in kinetic-colorimetric assay of bacterial endotoxins, J Pharm Biomed Analysis, 32: 1, pp. 495-503, (2003). [cited by applicant]
Haupt, H. et al., “Isolierung und physikalisch-chemische Charakterisierung der Cholinesterase aus Humanserum,” Blut, vol. 14, Issue 2, pp. 65-75, Nov. 1966. (English summary found within article on p. 75). [cited by applicant]
Heise et al., “Starlike Polymeric Architectures by Atom Transfer Radical Polymerization: Templates for the Production of Low Dielectric Constant Thin Films,” Macromolecules, Jan. 17, 2000, 33:2346-2354. [cited by applicant]
Heise, et al., “Investigation of the Initiation Behavior of a Dendritic 12-Arm Initiator in Atom Transfer Radical Polymerization,” Macromolecules, (2001), 34:11, pp. 3798-3801. [cited by applicant]
Heredia, et al., “In Situ Preparation of Protein—‘Smart’ Polymer Conjugates with Retention of Bioactivity,” J. Am. Chem. Soc., (2005), 127, pp. 16955-16960. [cited by applicant]
Hirayama, C. et al., “Chromatographic removal of endotoxin from protein solutions by polymer particles,” Journal of Chromatography B, vol. 781, Issues 1-2, pp. 419-432, Dec. 5, 2002. [cited by applicant]
Hoffmann, S. et al., “International validation of novel pyrogen tests based on human monocytoid cells,” Journal of Immunological Methods, vol. 298, Issues 1-2, pp. 161-173, Mar. 2005. [cited by applicant]
Holash, J et al. VEGF-Trap: A VEGF Blocker with Potent Antitumor Effects, PNAS, vol. 9, No. 17, pp. 11393-11398, (2002). [cited by applicant]
Hong, et al., “Preparation of Segmented Copolymers in the Presence of an Immobilized/Soluble Hybrid ATRP Catalyst System,” Macromolecules, (2003), 36:1, pp. 27-35. [cited by applicant]
Huang, Y-S. et al., “Engineering a pharmacologically superior form of granulocyte-colony-stimulating factor by fusion with gelatin-like-protein polymer,” European Journal of Pharmaceutics and Biopharmaceutics, vol. 74, … [cited by applicant]
Humphreys et al., “Alternative antibody FAB′ fragment PEGylation strategies: combination of strong reducing agents, disruption of the interchain disulphide bond and disulphide engineering,” Protein Engineering, Design &… [cited by applicant]
Huston, James S., “Protein engineering of single-chain Fv analogs and fusion proteins,” Methods of Enzymology, vol. 203, pp. 46-96, 1991. [cited by applicant]
Inada, Y. et al., “Application of Polyethylene glycol-modified enzymes in biotechnological processes: organic solvent-soluble enzymes”, TIBTECH, Jul. 1986, pp. 190-194. [cited by applicant]
Cited By (1)
US 12,643,958