IP Library › Granted Patent US 12,466,879
Granted Patent B2
US 12,466,879 · App. 18/165,233 · Granted Nov 11, 2025

Complement factor D antagonist antibodies and conjugates thereof

Inventors: Daniel Victor Perlroth (Palo Alto, CA); Wah Yuen To (San Mateo, CA); Hong Liang (Hillsborough, CA); Rachel Marie DeVay Jacobson (Belmont, CA); Fernando Corrêa (Hayward, CA)
Assignee: KODIAK SCIENCES INC.
C07K16/18A61K47/6843A61K47/6885C07K16/40C07K14/472C07K2317/24C07K2317/33C07K2317/34C07K2317/41C07K2317/51C07K2317/515C07K2317/55C07K2317/565C07K2317/734C07K2317/76C07K2317/92C07K2317/94C12Y304/21046
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Quick Facts
Patent No.
US 12,466,879
App. No.
18/165,233
Granted
Nov 11, 2025
Kind
B2
Abstract

The present invention provides antagonizing antibodies that bind to complement factor D (CFD), conjugates thereof, and methods of using same. The anti-CFD antibodies can be used therapeutically alone or in combination with other therapeutics to treat age related macular degeneration and other diseases.

Claims (89)

1 . A conjugate comprising:

an isolated antagonistic antibody that binds to complement factor D (CFD), the antibody comprising:

a CDR H 1 that is the CDR H 1 in SEQ ID NO: 520;

a CDR H 2 that is the CDR H 2 in SEQ ID NO: 520;

a CDR H 3 that is the CDR H 3 in SEQ ID NO: 520;

a CDR L 1 that is the CDR L 1 in SEQ ID NO: 525;

a CDR L 2 that is the CDR L 2 in SEQ ID NO: 525;

a CDR L 3 that is the CDR L 3 in SEQ ID NO: 525;

at least one of the following mutations (EU numbering): L234A, L235A, and G237A; and

at least one of the following mutations (EU numbering): Q347C or L443C; and

a polymer, wherein the polymer is covalently attached to the antibody.

2 . A conjugate comprising:

(a) an isolated antagonist antibody that specifically binds to complement factor D (CFD), wherein the antibody comprises:

a heavy chain variable region (VH) comprising:

a VH complementarity determining region 1 (CDR H 1) that is the CDR H 1 in SEQ ID NO: 520;

a CDR H 2 that is the CDR H 2 in SEQ ID NO: 520;

a CDR H 3 that is the CDRH3 in SEQ ID NO: 520; and

a light chain variable region (VL) comprising:

a VL complementarity determining region 1 (CDRL1) comprising H31, N33, G34 or E34 or F34 or S34, D35 or E35, T36 or S36 or V36, Y37, L38 or I38, and E39 (EU numbering);

a CDR L 2 comprising L51 or H51, 153 or V53, and K55 (EU numbering); and

a CDR L 3 comprising F94 or L94, Q95, G96, S97, V99 or N99 or Q99 or W99, P100, and P101 or V101 (EU numbering); and

(b) a phosphorylcholine containing polymer, wherein the polymer is covalently bonded to the antibody.

3 . The conjugate of claim 2 , wherein the conjugate is capable of blocking at least 80% of an interaction between CFD and C3bB.

4 . The conjugate of claim 2 , wherein the polymer is covalently bonded to the antibody at a non-native cysteine outside a variable region of the antibody.

5 . The conjugate of claim 2 , wherein the polymer is formed by 2 (methacryloyloxy)ethyl (2-(trimethylammonio)ethyl) phosphate (MPC) monomers.

6 . The conjugate of claim 2 , wherein the polymer has a peak molecular weight between 300,000 and 1,750,000 Daltons as measured by size exclusion chromatography-multi angle light scattering (hereinafter “SEC-MALS”).

7 . The conjugate of claim 2 , wherein the polymer has 2 or more arms.

8 . The conjugate of claim 2 , wherein the polymer is covalently bonded to a sulfhydryl group from a cysteine residue on the heavy chain.

9 . The conjugate of claim 8 , wherein the polymer is covalently bonded to a sulfhydryl group from a cysteine residue at position 347 or 443 (EU numbering).

10 . The conjugate of claim 2 , wherein the conjugate has a molecular weight between about 350,000 and 1,900,000 Daltons.

11 . The conjugate of claim 2 , wherein

the polymer has 9 arms; and

the polymer has a molecular weight of between about 600,000 to about 900,000 Da.

12 . The conjugate of claim 2 , which has the following structure:

wherein:

each heavy chain of the antibody is denoted by the letter H, and each light chain of the antibody is denoted by the letter L,

the polymer is bonded to the antibody through the sulfhydryl of C443 (EU numbering), which bond is depicted on one of the heavy chains,

PC is

 wherein the curvy line indicates the point of attachment to the rest of the polymer,

X is:

a) OR, wherein R is: methyl; ethyl; propyl; or isopropyl;

b) H; or

c) any halogen, and

n1, n2, n3, n4, n5, n6, n7, n8 and n9 are the same or different such that the sum of n1, n2, n3, n4, n5, n6, n7, n8 and n9 is 2500 plus or minus 15%.

13 . A pharmaceutical composition comprising a conjugate of claim 2 , and a pharmaceutically acceptable carrier.

14 . The conjugate of claim 2 , wherein

(a) when bound, the antibody is within 3 Å of residue 209 of SEQ ID NO: 1 of CFD, or

(b) when bound, the antibody is within 3 Å of residue 156 of SEQ ID NO: 1 of CFD, or

(c) the antibody binds to one or more of residues 156 or 209 of SEQ ID NO: 1 of CFD, or

(d) when bound to CFD, the antibody is not within 6 angstroms of at least one of 117, 118, and 156 of SEQ ID NO: 1.

15 . The conjugate of claim 2 , wherein the isolated antagonist antibody

(a) specifically binds to complement factor D (CFD) and directly inhibits a proteolytic activity of CFD, or

(b) specifically binds to complement factor D (CFD), inhibits a proteolytic activity of CFD, and inhibits CFD binding to C3bB complex, or

(c) specifically binds to complement factor D (CFD), wherein the antibody does not bind a human CFD mutant comprising mutations R157A and R207A, or

(d) binds an epitope on human CFD, wherein the epitope excludes positions R157 and R207.

16 . The conjugate of claim 2 , wherein the light chain variable region of the antibody comprises three complementarity determining regions (CDRs) comprising the amino acid sequences shown in SEQ ID NO: 525.

17 . The conjugate of claim 2 , wherein the heavy chain variable region (VH) of the antibody comprises three CDRs comprising the amino acid sequences shown in SEQ ID NO: 541, SEQ ID NO: 542, and SEQ ID NO: 543, and the light chain variable region (VL) of the antibody comprises three CDRs comprising the amino acid sequences shown in SEQ ID NO: 544, SEQ ID NO: 545, and SEQ ID NO: 546.

18 . The conjugate of claim 17 , wherein the VH comprises the amino acid sequences shown in SEQ ID NO: 520, and the VL comprises three CDRs comprising the amino acid sequences shown in SEQ ID NO: 544, SEQ ID NO: 545 and SEQ ID NO: 546.

19 . The conjugate of claim 18 , wherein the VL comprises the amino acid sequence shown in SEQ ID NO: 525.

20 . The conjugate of claim 2 , wherein the antibody comprises a heavy chain comprising the amino acid sequence shown in SEQ ID NO: 183, with or without the C-terminal lysine, and a light chain comprising the amino acid sequence shown in SEQ ID NO: 184.

21 . The conjugate of claim 12 , wherein X is Br.

22 . A conjugate comprising:

an isolated antagonist antibody that specifically binds to complement factor D (CFD), the antibody comprising:

a heavy chain variable region (VH) comprising 3 CDRs of the CDRs in SEQ ID NO: 339; and a light chain variable region (VH) comprising 3 CDRs of the CDRs in SEQ ID NO: 340; or

a VH comprising 3 CDRs of the CDRs in SEQ ID NO: 343; and a VL comprising 3 CDRs of the CDRs in SEQ ID NO: 344; or

a VH comprising 3 CDRs of the CDRs in SEQ ID NO: 435; and a VL comprising 3 CDRs of the CDRs in SEQ ID NO: 436; or

a VH comprising 3 CDRs of the CDRs in SEQ ID NO: 437; and a VL comprising 3 CDRs of the CDRs in SEQ ID NO: 438; or

a VH comprising 3 CDRs of the CDRs in SEQ ID NO: 441; and a VL comprising 3 CDRs of the CDRs in SEQ ID NO: 442; or

a VH comprising 3 CDRs of the CDRs in SEQ ID NO: 443; and a VL comprising 3 CDRs of the CDRs in SEQ ID NO: 444; or

a VH comprising 3 CDRs of the CDRs in SEQ ID NO: 445; and a VL comprising 3 CDRs of the CDRs in SEQ ID NO: 446; or

a VH comprising 3 CDRs of the CDRs in SEQ ID NO: 447; and a VL comprising 3 CDRs of the CDRs in SEQ ID NO: 448; or

a VH comprising 3 CDRs of the CDRs in SEQ ID NO: 351; and a VL comprising 3 CDRs of the CDRs in SEQ ID NO: 352; or

a VH comprising 3 CDRs of the CDRs in SEQ ID NO: 373; and a VL comprising 3 CDRs of the CDRs in SEQ ID NO: 374; or

a VH comprising 3 CDRs of the CDRs in SEQ ID NO: 387; and a VL comprising 3 CDRs of the CDRs in SEQ ID NO: 388; or

a VH comprising 3 CDRs of the CDRs in SEQ ID NO: 385; and a VL comprising 3 CDRs of the CDRs in SEQ ID NO: 386; or

a VH comprising 3 CDRs of the CDRs in SEQ ID NO: 389; and a VL comprising 3 CDRs of the CDRs in SEQ ID NO: 390; or

a VH comprising 3 CDRs of the CDRs in SEQ ID NO: 391; and a VL comprising 3 CDRs of the CDRs in SEQ ID NO: 392; or

a VH comprising 3 CDRs of the CDRs in SEQ ID NO: 509; and a VL comprising 3 CDRs of the CDRs in SEQ ID NO: 510; or

a VH comprising 3 CDRs of the CDRs in SEQ ID NO: 485; and a VL comprising 3 CDRs of the CDRs in SEQ ID NO: 486; or

a VH comprising 3 CDRs of the CDRs in SEQ ID NO: 495; and a VL comprising 3 CDRs of the CDRs in SEQ ID NO: 496; or

a VH comprising 3 CDRs of the CDRs in SEQ ID NO: 471; and a VL comprising 3 CDRs of the CDRs in SEQ ID NO: 472; or

a VH comprising 3 CDRs of the CDRs in SEQ ID NO: 337; and a VL comprising 3 CDRs of the CDRs in SEQ ID NO: 338; or

a VH comprising 3 CDRs of the CDRs in SEQ ID NO: 423; and a VL comprising 3 CDRs of the CDRs in SEQ ID NO: 424; or

a VH comprising 3 CDRs of the CDRs in SEQ ID NO: 439; and a VL comprising 3 CDRs of the CDRs in SEQ ID NO: 440; or

a VH comprising 3 CDRs of the CDRs in SEQ ID NO: 459; and a VL comprising 3 CDRs of the CDRs in SEQ ID NO: 460; or

a VH comprising 3 CDRs of the CDRs in SEQ ID NO: 477; and a VL comprising 3 CDRs of the CDRs in SEQ ID NO: 478; or

a VH comprising 3 CDRs of the CDRs in SEQ ID NO: 461; and a VL comprising 3 CDRs of the CDRs in SEQ ID NO: 462; or

a VH comprising 3 CDRs of the CDRs in SEQ ID NO: 493; and a VL comprising 3 CDRs of the CDRs in SEQ ID NO: 494; and

a phosphorylcholine containing polymer, wherein the polymer is covalently bonded to the antibody.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 24, 2025
From: PERLROTH, D. VICTOR; TO, WAH YUEN; LIANG, HONG; JACOBSON, RACHEL MARIE DEVAY; CORREA, FERNANDO
To: KODIAK SCIENCES INC.
Reel/Frame 070307/0275 →
Continuity (3)
Division 15952092 · Apr 12, 2018
Provisional Application 62485718 · Apr 14, 2017
Related Publication 20230382983A1 · Nov 30, 2023
References Cited (311)
US 4485045A · Regen · 1984 [cited by applicant]
US 4544545A · Ryan et al. · 1985 [cited by applicant]
US 4634664A · Oestberg · 1987 [cited by applicant]
US 4634666A · Engleman et al. · 1987 [cited by applicant]
US 4683195A · Mullis et al. · 1987 [cited by applicant]
US 4683202A · Mullis · 1987 [cited by applicant]
US 4754065A · Levenson et al. · 1988 [cited by applicant]
US 4777127A · Suni et al. · 1988 [cited by applicant]
US 4800159A · Mullis et al. · 1989 [cited by applicant]
US 4816567A · Cabilly et al. · 1989 [cited by applicant]
US 4892538A · Aebischer et al. · 1990 [cited by applicant]
US 5013556A · Woodle et al. · 1991 [cited by applicant]
US 5047335A · Paulson et al. · 1991 [cited by applicant]
US 5219740A · Dusty et al. · 1993 [cited by applicant]
US 5225539A · Winter · 1993 [cited by applicant]
US 5278299A · Wong et al. · 1994 [cited by applicant]
US 5283187A · Aebischer et al. · 1994 [cited by applicant]
US 5422120A · Kim et al. · 1995 [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 5580859A · Felgner et al. · 1996 [cited by applicant]
US 5585089A · Queen et al. · 1996 [cited by applicant]
US 5624821A · Winter et al. · 1997 [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 5770429A · Lonberg et al. · 1998 [cited by applicant]
US 5789650A · Lonberg et al. · 1998 [cited by applicant]
US 5814318A · Lonberg et al. · 1998 [cited by applicant]
US 5814482A · Dubensky, Jr. 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 6376471B1 · Lawrence, III et al. · 2002 [cited by applicant]
US 6407213B1 · Carter et al. · 2002 [cited by applicant]
US 6413942B1 · Felgner et al. · 2002 [cited by applicant]
US 6436908B1 · Koch et al. · 2002 [cited by applicant]
US 6624821B1 · Shin et al. · 2003 [cited by applicant]
US 6881557B2 · Foote · 2005 [cited by applicant]
US 6956107B2 · Fung · 2005 [cited by examiner]
US 7521541B2 · Eigenbrot et al. · 2009 [cited by applicant]
US 7667004B2 · Zhong 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 8067002B2 · An et al. · 2011 [cited by applicant]
US 8273352B2 · Huang et al. · 2012 [cited by applicant]
US 8455622B2 · McDonagh et al. · 2013 [cited by applicant]
US 8753625B2 · Fung et al. · 2014 [cited by applicant]
US 8765432B2 · Charles · 2014 [cited by applicant]
US 8846021B2 · Charles · 2014 [cited by applicant]
US 8969526B2 · Baehner et al. · 2015 [cited by applicant]
US 9840553B2 · Perlroth et al. · 2017 [cited by applicant]
US 10363290B2 · Perlroth et al. · 2019 [cited by applicant]
US 10407510B2 · Kelley 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 · 2023 [cited by examiner]
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 20030235536A1 · Blumberg et al. · 2003 [cited by applicant]
US 20050041080A1 · Hall et al. · 2005 [cited by applicant]
US 20060167230A1 · Koga et al. · 2006 [cited by applicant]
US 20080269318A1 · Romano · 2008 [cited by applicant]
US 20090060906A1 · Barry et al. · 2009 [cited by applicant]
US 20090249503A1 · Rosendahl · 2009 [cited by applicant]
US 20100166700A1 · Charles · 2010 [cited by examiner]
US 20100291065A1 · Kabanov et al. · 2010 [cited by applicant]
US 20110165648A1 · Campagne · 2011 [cited by examiner]
US 20120100166A1 · Roschke et al. · 2012 [cited by applicant]
US 20120213705A1 · Dimasi et al. · 2012 [cited by applicant]
US 20130045522A1 · Charles et al. · 2013 [cited by applicant]
US 20140024776A1 · Charles et al. · 2014 [cited by applicant]
US 20140065137A1 · Huang et al. · 2014 [cited by applicant]
US 20150004128A1 · Charles et al. · 2015 [cited by applicant]
US 20150050714A1 · Charles · 2015 [cited by applicant]
US 20150093390A1 · Bansal · 2015 [cited by applicant]
US 20150158952A1 · Mao et al. · 2015 [cited by applicant]
US 20150337053A1 · McCarthy et al. · 2015 [cited by applicant]
US 20150376271A1 · Perlroth · 2015 [cited by examiner]
US 20160017052A1 · Kelley · 2016 [cited by examiner]
US 20160287715A1 · Charles 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 20180319893A1 · Stephen et al. · 2018 [cited by applicant]
US 20190270806A1 · Jacobson et al. · 2019 [cited by applicant]
US 20190330335A1 · Schwabe 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 20230173081A1 · Charles et al. · 2023 [cited by applicant]
US 20230250133A1 · Zurbriggen 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]
US 20240368267A1 · Jacobson et al. · 2024 [cited by applicant]
CN 106905431 · 2017 [cited by applicant]
EP 0345242 · 1989 [cited by applicant]
EP 0282160 · 1995 [cited by applicant]
EP 0524968 · 1995 [cited by applicant]
WO WO9007936 · 1990 [cited by applicant]
WO WO9011092 · 1990 [cited by applicant]
WO WO9100904 · 1991 [cited by applicant]
WO WO9102805 · 1991 [cited by applicant]
WO WO9110741 · 1991 [cited by applicant]
WO WO9114445 · 1991 [cited by applicant]
WO WO9117271 · 1991 [cited by applicant]
WO WO9201047 · 1992 [cited by applicant]
WO WO9303769 · 1993 [cited by applicant]
WO WO9310218 · 1993 [cited by applicant]
WO WO9311230 · 1993 [cited by applicant]
WO WO9312227 · 1993 [cited by applicant]
WO WO9319191 · 1993 [cited by applicant]
WO WO9325234 · 1993 [cited by applicant]
WO WO9325673 · 1993 [cited by applicant]
WO WO9325698 · 1993 [cited by applicant]
WO WO9403622 · 1994 [cited by applicant]
WO WO9412649 · 1994 [cited by applicant]
WO WO9416748 · 1994 [cited by applicant]
WO WO9423697 · 1994 [cited by applicant]
WO WO9428938 · 1994 [cited by applicant]
WO WO9500655 · 1995 [cited by applicant]
WO WO9507994 · 1995 [cited by applicant]
WO WO9511984 · 1995 [cited by applicant]
WO WO9513796 · 1995 [cited by applicant]
WO WO9530763 · 1995 [cited by applicant]
WO WO9617072 · 1996 [cited by applicant]
WO WO9714702 · 1997 [cited by applicant]
WO WO9714703 · 1997 [cited by applicant]
WO WO9742338 · 1997 [cited by applicant]
WO WO9942133 · 1999 [cited by applicant]
WO WO0009560 · 2000 [cited by applicant]
WO WO2004020405 · 2004 [cited by applicant]
WO WO2007100902 · 2007 [cited by applicant]
WO WO2008020827 · 2008 [cited by applicant]
WO WO2008055206 · 2008 [cited by applicant]
WO WO2008155134 · 2008 [cited by applicant]
WO WO2009052249 · 2009 [cited by applicant]
WO WO2009052439 · 2009 [cited by applicant]
WO WO2009134711 · 2009 [cited by applicant]
WO WO2011057014 · 2011 [cited by applicant]
WO WO2011075185 · 2011 [cited by applicant]
WO WO2011075736 · 2011 [cited by applicant]
WO WO2011101284 · 2011 [cited by applicant]
WO WO2011130694 · 2011 [cited by applicant]
WO WO2012145746 · 2012 [cited by applicant]
WO WO2013059137 · 2013 [cited by applicant]
WO WO2013093809 · 2013 [cited by applicant]
WO WO2013093809A1 · 2013 [cited by examiner]
WO WO2015035342 · 2015 [cited by applicant]
WO WO2015168468 · 2015 [cited by applicant]
WO WO2015200905 · 2015 [cited by applicant]
WO WO2016061562 · 2016 [cited by applicant]
WO WO2017075173 · 2017 [cited by applicant]
WO WO2017117464 · 2017 [cited by applicant]
WO WO2017129064 · 2017 [cited by applicant]
WO WO2018191548 · 2018 [cited by applicant]
WO WO2019169341 · 2019 [cited by applicant]
Burgess et al., Journal of Cell Biology 111:2129-2138 (Year: 1990). [cited by examiner]
Nilsen et al., Communications Biology 3(181): 1-11 (Year: 2020). [cited by examiner]
Office Action for Australian Application No. AU 2022201163 in 4 pages, dated Apr. 26, 2024. [cited by applicant]
Office Action for Canadian Application No. CA 3,059,938 in 20 pages, dated Oct. 16, 2023. [cited by applicant]
U.S. Appl. No. 09/253,689, filed Feb. 20, 1999, Fung et al. [cited by applicant]
Anderson, W.F., “Human gene therapy,” Science, May 8, 1992, vol. 256, No. 5058, pp. 808-813. [cited by applicant]
Binder, S et al., “Transplantation of the RPE in AMD”, Progress in Retinal and Eye Research, 2007, vol. 26, pp. 516-554. [cited by applicant]
Boyd et al., “The effect of the removal of sialic acid, galactose and total carbohydrate on the functional activity of Campath-1H”, Molecular Immunology, Dec. 1995, vol. 32, pp. 1311-1318. [cited by applicant]
Capel, P. J. A. et al., “Heterogeneity of human IgG Fc receptors”, Immunomethods, Feb. 1994, vol. 4(1), pp. 25-34. [cited by applicant]
Capon, D. et al., “Designing CD4 immunoadhesins for AIDS therapy,” Nature, 1989, vol. 337, pp. 525-531. [cited by applicant]
Chiou, H. et al., “In Vivo Gene Therapy via Receptor-Mediated DNA Delivery”, in Gene Therapeutics: Methods and Applications of Direct Gene Transfer, J.A. Wolff, ed., 1994, in 14 pages. [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]
Connelly, S. et al., “In Vivo Gene Delivery and Expression of Physiological Levels of Functional Human Factor VIII in Mice”, Human Gene Therapy, 1995, vol. 6, pp. 185-193. [cited by applicant]
Curiel, D. et al., “High-Efficiency Gene Transfer Mediated by Adenovirus Coupled to DNA-Polylysine Complexes”, Human Gene Therapy, 1992, vol. 3(2), pp. 147-154. [cited by applicant]
Dayhoff, M.O. (ed.) Atlas of Protein Sequence and Structure, National Biomedical Research Foundation, Washington DC vol. 5, Suppl. 3, pp. 345-358. 1978. [cited by applicant]
De Haas et al., “Fc gamma receptors of phagocytes”, Journal of Laboratory and Clinical Medicine, 126(4): dated Oct. 1995, pp. 330-341. [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]
Edwards et al., “The Remarkable Flexibility of the Human Antibody Repertoire; Isolation of Over One Thousand Different Antibodies to a Single Protein, BLyS”, J. Mol. Biol., vol. 334, pp. 103-118, 2003. [cited by applicant]
Eppstein et al., “Biological activity of liposome-encapsulated murine interferon gamma is mediated by a cell membrane receptor”, Proc. Natl. Acad. Sci. USA, vol. 82: dated Jun. 1985 pp. 3688-3692. [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]
Findeis et al., “Targeted delivery of DNA for gene therapy via receptors” Trends Biotechnol., 1993, 11: pp. 202-205. [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]
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]
Guyer et al., “Immunoglobulin Binding by Mouse Intestinal Epithelial Cell Receptors”, The Journal of Immunology, 117(2): dated Aug. 1, 1976, pp. 587-893. [cited by applicant]
Hein J., 1990, Unified Approach to Alignment and Phylogenies pp. 626-645 Methods in Enzymology vol. 183, Academic Press, Inc., San Diego, CA. [cited by applicant]
Higgins, D.G. and Sharp, P.M., “Fast and sensitive multiple sequence alignments on a microcomputer” CABIOS 5: dated 1989, pp. 151-153. [cited by applicant]
Hinton et al., “Engineered human IgG antibodies with longer serum half-lives in primates”, Journal of Biological Chemistry, 279(8): dated Feb. 20, 2004 in 5 pages. [cited by applicant]
Hsu et al., “Differential N-Glycan Patterns of Secreted and Intracellular IgG Produced in Trichoplusia ni Cells” Journey of Biol. Chem. vol. 272: dated 1997, pp. 9062-9070. [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]
Hwang et al., “Hepatic uptake and degradation of unilamellar sphingomyelin/cholesterol liposomes: a kinetic study”, Proceedings of the National Academy of Sciences of the United States of America, 77(7): dated Jul. 1980… [cited by applicant]
Iwahashi, M. et al., “CDR substitutions of a humanized monoclonal antibody (CC49): contributions of individual CDRs to antigen binding and immunogenicity,” Mol. Immunol. 36: Issue 15-16, 1079-1091, 1999. [cited by applicant]
Jaffe, G. et al., “Intraocular drug delivery,” CRC Press, Mar. 2006 (Table of Contents only). [cited by applicant]
Jefferis et al., “Glycosylation of Antibody Molecules: Structural and Functional Significance”, Antibody Engineering, vol. 65: dated 1997, pp. 111-128. [cited by applicant]
Johnson et al., “Kabat Database and its applications: 30 years after the first variability plot”, Nucleic Acids Research, 28(1): Jan. 1, 2000, pp. 214-218. [cited by applicant]
Joralemon et al., PEGylated Polymers for Medicine From Conjugation to Self-Assembled Systems, Chemical Communications, vol. 46, No. 9, pp. 1377, 2010. [cited by applicant]
Kabat, E.A. et al., “Sequences of proteins of immunological interest,” in 10 pages, 1991 (Table of Contents only). [cited by applicant]
Kaplitt, “Long-term gene expression and phenotypic correction using adeno-associated virus vectors in the mammalian brain” Nature Genetics, 1994, 8:148. [cited by applicant]
Katschke, K. et al., “Inhibiting Alternative Pathway Complement Activation by Targeting the Factor D Exosite—Supplementary Material”, The Journal of Biological Chemistry, Apr. 2012, vol. 287, No. 16, in 11 pages. [cited by applicant]
Katschke, K. et al., “Inhibiting Alternative Pathway Complement Activation by Targeting the Factor D Exosite”, The Journal of Biological Chemistry, Apr. 2012, vol. 287, No. 16, pp. 12886-12892. [cited by applicant]
Kim et al., “Identifying amino acid residues that influence plasma clearance of murine IgG1 fragments by site-directed mutagenesis”, European Journal of Immunology, 24(3): dated Mar. 1994. [cited by applicant]
Kim, J.K. et al., “Localization of the site of the murine IgG1 molecule that is involved in binding to the murine intestinal Fc receptor”, European Journal of Immunology, Oct. 1994, vol. 24(10), pp. 2429-2434. [cited by applicant]
Kimura, “Retroviral Delivery of DNA into the Livers of Transgenic Mice Bearing Premalignant and Malignant Hepatocellular Carcinomas” Human Gene Therapy, 1994, 5(7): pp. 845-852. [cited by applicant]
Klein R, Klein BE, Jensen SC, Meuer SM. 1997. The five-year incidence and progression of age-related maculopathy: The Beaver Dam Eye Study. Ophthal. 104:7-21. [cited by applicant]
Kohler et al., “Continuous cultures of fused cells secreting antibody of predefined specificity”, Nature, vol. 256: dated 1975, pp. 495-497. [cited by applicant]
Kunik et al., “Paratome: an online tool for systematic identification of antigen-binding regions in antibodies based on sequence or structure”, Nucleic Acids Research, vol. 40: Jun. 6, 2012, W521-524. [cited by applicant]
Lazar et al., “Engineered antibody Fc variants with enhanced effector function”, Proc Natl Acad Sci U S A, 103(11): dated Mar. 14, 2006 in 6 pages. [cited by applicant]
Lefranc et al., “IMGT unique numbering for immunoglobulin and T cell receptor variable domains and Ig superfamily V-like domains”, Developmental and Comparative Immunology, vol. 27: dated 2003, pp. 55-77. [cited by applicant]
Lloyd et al., “Modeling the human immune response: performance of a 1011 human antibody repertoire against a broad panel of therapeutically relevant antigens”, Protein Engineering Design & Selection, vol. 22, No. 3, pp.… [cited by applicant]
Maccallum, R. et al., Antibody-Antigen Interactions: Contact Analysis and Binding Site Topography, J. Mol Biol., vol. 262, pp. 732-745, (1996). [cited by applicant]
Makabe et al., “Thermodynamic Consequences of Mutations in Vernier Zone Residues of a Humanized Anti-human Epidermal Growth Factor Receptor Murine Antibody, 528”, Journal of Biological Chemistry, vol. 283: dated Jan. 11… [cited by applicant]
Martin et al., “Modeling antibody hypervariable loops: A combined algorithm”, Proc. Natl. Acad. Sci. USA, vol. 86: dated Dec. 1989, pp. 9268-9272. [cited by applicant]
Mccafferty et al., “Phage antibodies: filamentous phage displaying antibody variable domains”, Nature, vol. 348: dated 1990, pp. 552-554. [cited by applicant]
Mcpherson, D. et al., “Production and Purification of a Recombinant Elastomeric Polypeptide, G-(VPGVG)19-VPGV, from [cited by applicant]
Neuberger, M., “Generating high-avidity human Mabs in mice,” Nature Biotechnology, vol. 14, pp. 826, 1996. [cited by applicant]
Östberg, L. et al., “Human X (mouse X human) hybridomas stably producing human antibodies,” Hybridoma, vol. 2, No. 4, pp. 361-367, 1983. [cited by applicant]
Padlan, Eduardo A., “A possible procedure for reducing the immunogenicity of antibody variable domains while preserving their ligand-binding properties,” Molecular Immunology, vol. 28, Issues 4-5, pp. 489-498, Apr.-May … [cited by applicant]
Paul, “Fv Structure and Diversity in Three Dimensions,” Fundamental Immunology, 1993, 3rd Edition, pp. 292-295. [cited by applicant]
Philip, “Efficient and sustained gene expression in primary T lymphocytes and primary and cultured tumor cells mediated by adeno-associated virus plasmid DNA complexed to cationic liposomes.” Mol. Cell Biol., 1994, 14(4… [cited by applicant]
Piatesi, A. et al., “Immunological Optimization of a Generic Hydrophobic Pocket for High Affinity Hapten Binding and Diels-Alder Activity”, ChemBio Chem, 2004, vol. 5, pp. 460-466. [cited by applicant]
Ravetch et al., “FC Receptors,” 1991, Ann. Rev. Immunol., vol. 9:457-92. [cited by applicant]
RecName: Full=Complement factor D; EC=3.4.21.46; AltName: Full=Adipsin; AltName: Full=C3 convertase activator; AltName: Full=Properdin factor D; Flags: Precursor, Uniprot, Jul. 21, 1986 (Jul. 21, 1986), XP002614847, [re… [cited by applicant]
Robinson, D.F, “Comparison of Labeled Trees with Valency Three,” Journal of Combinational Theory 11: pp. 105-119 (1971). [cited by applicant]
Roitt, I.M., “Immunology—Second Edition”, Gower Medical Publishing, 1989, p. 5.8, 5.9. [cited by applicant]
Rudikoff, S. et al., Single Amino Acid Substitution Altering Antigen-Binding Specificity, Proc Natl. Acad. Sci. USA, vol. 79, pp. 1979-1983, (1982). [cited by applicant]
Saitou, N., Nei, M., “The neighbor-joining method: a new method for reconstructing phylogenetic trees.” Mol. Biol. Evol. vol. 4: dated 1987, pp. 406-425. [cited by applicant]
Samudrala et al., “Ab initio protein structure prediction using a combined hierarchical approach”, Proteins, Structure, and Genetics Suppl, 37(S3): dated 1999, pp. 194-198. [cited by applicant]
Schellenberger, V. et al., “A recombinant polypeptide extends the in vivo half-life of peptides and proteins in a tunable manner,” Nature Biotechnology, vol. 27, pp. 1186-1190, 2009. [cited by applicant]
Schlapschy, M. et al., “Fusion of a recombinant antibody fragment with a homo-amino-acid polymer: effects on biophysical properties and prolonged plasma half-life,” Protein Eng Des Sel, vol. 20, Issue 6, pp. 273-284, Ju… [cited by applicant]
Tamura, M. et al., “Structural correlates of an anticarcinoma antibody: Identification of specificity-determining residues (SDRs) and development of a minimally immunogenic antibody variant by retention of SDRs only,” T… [cited by applicant]
Tonkinson, J. et al., “New Drugs: Antisense Oligodeoxynucleotides as Clinical Therapeutic Agents,” Cancer Investigation, vol. 14, No. 1, pp. 54-65, 1996. [cited by applicant]
Umana et al., “Engineered glycoforms of an antineuroblastoma IgG1 with optimized antibody-dependent cellular cytotoxic activity.” 1999, Nature Biotech. 17:176-180. [cited by applicant]
Vajdos, F. et al., “Comprehensive functional maps of the antigen-binding site of an anti-ErbB2 antibody obtained with shotgun scanning mutagenesis,” Journal of Molecular Biology, vol. 320, Issue 2, pp. 415-428, Jul. 5, … [cited by applicant]
Wagner, E. et al., “Transferrin-polycation conjugates as carriers for DNA uptake into cells,” Proc. Natl. Acad. Sci. USA, vol. 87, No. 9, pp. 3410-3414, May 1, 1990. [cited by applicant]
Wilbur, W.J. and Lipman, D.J., “Rapid similarity searches of nucleic acid and protein data banks” 1983, Proc. Natl. Acad. Sci. USA 80: pp. 726-730. [cited by applicant]
Wittwer et al., “Glycosylation at Asn-184 inhibits the conversion of single-chain to two-chain tissue-type plasminogen activator by plasmin”, Biochemistry, 29(17): dated May 1, 1990, pp. 4175-4180. [cited by applicant]
Woffendin, “Nonviral and viral delivery of a human immunodeficiency virus protective gene into primary human T cells” Proc. Natl. Acad. Sci., 1994, 91: pp. 11581-11585. [cited by applicant]
Wright et al., “Effect of glycosylation on antibody function: implications for genetic engineering”, Trends Biotechnol, 15(1): dated Jan. 1997, pp. 26-32. [cited by applicant]
Wu et al., “Incorporation of Adenovirus into a Ligand-based DNA Carrier System Results in Retention of Original Receptor Specificity and Enhances Targeted Gene Expression” J. Biol. Chem., 1994, 269 (15): pp. 11542-11546. [cited by applicant]
Wu et al., “Receptor-mediated Gene Delivery and Expression in Vivo” J. Biol. Chem., 1988, 263. [cited by applicant]
Wu et al., “Receptor-mediated Gene Delivery in Vivo” J. Biol. Chem., 1991, 266, pp. 14338-14342. [cited by applicant]
Wu, “Targeting Genes: Delivery and Persistent Expression of a Foreign Gene Driven by Mammalian Regulatory Elements in Vivo” J. Biol. Chem., 1989, 264(29):16985-19687. [cited by applicant]
Wu, G.Y. et al., “Receptor-mediated in vitro gene transformation by a soluble DNA carrier system,” Journal of Biological Chemistry, vol. 262, pp. 4429-4432, Apr. 5, 1987. [cited by applicant]
Wu, H et al., Humanization of a Murine Monoclonal Antibody by Simultaneous Optimization of Framework and CDR Residues, J. Mol. Biol., vol. 294, pp. 151-162, (1999). [cited by applicant]
Wyss et al., “The structural role of sugars in glycoproteins”, Current Opin. Biotech. 1996, vol. 7, pp. 409-416. [cited by applicant]
Yeh, P. et al., “Design of yeast-secreted albumin derivatives for human therapy: biological and antiviral properties of a serum albumin-CD4 genetic conjugate,” Proc Natl Acad Sci USA, vol. 89, No. 5, pp. 1904-1908, Mar.… [cited by applicant]
Zenke et al., “Receptor-mediated endocytosis of transferrin-polycation conjugates: an efficient way to introduce DNA into hematopoietic cells.” Proc. Natl. Acad. Sci. USA, 1990, 87(10):3655-3659. [cited by applicant]
Office Action for Australian Application No. AU 2018250695 in 4 pages, dated Feb. 22, 2021. [cited by applicant]
Office Action for Australian Application No. AU 2018250695 in 5 pages, dated Nov. 19, 2021. [cited by applicant]
Office Action for Australian Application No. AU 2018250695 in 5 pages, dated Feb. 9, 2022. [cited by applicant]
Office Action for Canadian Application No. 3,059,938 dated Sep. 30, 2020. [cited by applicant]
Office Action for Canadian Application No. CA 3,059,938 in 4 pages, dated Sep. 27, 2021. [cited by applicant]
Office Action for Canadian Application No. CA 3,059,938 in 4 pages, dated Aug. 12, 2022. [cited by applicant]
Extended Search Report for European Application No. 18784891.6 in 15 pages, dated Jan. 21, 2021. [cited by applicant]
Office Action for European Application No. EP 18784891.6 in 6 pages, dated Jan. 2, 2023. [cited by applicant]
Invitation to Pay Additional Fees for PCT/US2018/027378 dated Aug. 1, 2018. [cited by applicant]
International Search Report and Written Opinion for PCT/US2018/027378 dated Sep. 27, 2018. [cited by applicant]
International Preliminary Report on Patentability for PCT/US2018/027378 dated Oct. 24, 2019. [cited by applicant]
Restriction Requirement for U.S. Appl. No. 15/952,092 dated Mar. 3, 2020. [cited by applicant]
Office Action for U.S. Appl. No. 15/952,092 dated Jun. 30, 2020. [cited by applicant]
Final Office Action for U.S. Appl. No. 15/952,092 dated Nov. 27, 2020. [cited by applicant]
Office Action for U.S. Appl. No. 15/952,092 in 29 pages, dated May 21, 2021. [cited by applicant]
Office Action for U.S. Appl. No. 15/952,092 in 17 pages, dated Sep. 13, 2021. [cited by applicant]
Notice of Allowance for U.S. Appl. No. 15/952,092 in 10 pages, dated Feb. 8, 2022. [cited by applicant]
Notice of Allowance for U.S. Appl. No. 15/952,092 in 9 pages, dated May 27, 2022. [cited by applicant]
Notice of Allowance for U.S. Appl. No. 15/952,092 in 9 pages, dated Oct. 17, 2022. [cited by applicant]
Notice of Allowance for U.S. Appl. No. 15/952,092 in 3 pages, dated Jan. 19, 2023. [cited by applicant]
Office Action for U.S. Appl. No. 15/820,325 dated Jul. 29, 2019. [cited by applicant]
File History of U.S. Appl. No. 15/952,092, filed Apr. 12, 2018. [cited by applicant]
File History of U.S. Appl. No. 15/394,500, filed Dec. 29, 2016. [cited by applicant]
File History of U.S. Appl. No. 13/959,563, filed Aug. 5, 2013. [cited by applicant]
File History of U.S. Appl. No. 14/456,875, filed Aug. 11, 2014. [cited by applicant]
File History of U.S. Appl. No. 16/424,265, filed Aug. 11, 2014. [cited by applicant]
File History of U.S. Appl. No. 12/281,071, filed Aug. 28, 2008. [cited by applicant]
File History of U.S. Appl. No. 14/265,174, filed Apr. 29, 2014. [cited by applicant]
File History of U.S. Appl. No. 15/182,278, filed Jun. 14, 2016. [cited by applicant]
File History of U.S. Appl. No. 13/515,913, filed Aug. 27, 2012. [cited by applicant]
File History of U.S. Appl. No. 13/516,173, filed Aug. 27, 2012. [cited by applicant]
File History of U.S. Appl. No. 15/099,234, filed Apr. 14, 2016. [cited by applicant]
File History of U.S. Appl. No. 13/901,483, filed May 23, 2013. [cited by applicant]
File History of U.S. Appl. No. 15/368,376, filed Dec. 2, 2016. [cited by applicant]
File History of U.S. Appl. No. 13/641,342, filed Dec. 2, 2016. [cited by applicant]
File History of U.S. Appl. No. 16/781,869, filed Mar. 2, 2016. [cited by applicant]
File History of U.S. Appl. No. 14/916,180, filed Mar. 2, 2016. [cited by applicant]
File History of U.S. Appl. No. 16/795,450, filed Jun. 29, 2015. [cited by applicant]
File History of U.S. Appl. No. 15/820,325, filed Nov. 21, 2017. [cited by applicant]
File History of U.S. Appl. No. 14/932,913, filed Nov. 4, 2015. [cited by applicant]
File History of U.S. Appl. No. 16/402,602, filed Nov. 4, 2015. [cited by applicant]
File History of U.S. Appl. No. 16/290,128, filed Mar. 1, 2019. [cited by applicant]
Office Action for Australian Application No. AU 2022201163 in 4 pages, dated Oct. 29, 2024. [cited by applicant]
Office Action for Canadian Application No. CA 3,059,938 in 3 pages, dated Dec. 30, 2024. [cited by applicant]
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