Granted Patent
B2
US 12,281,165 · App. 17/677,283 · Granted Apr 22, 2025
Anti-B7-H4 antibodies and immunoconjugates
Inventors:
Steven R. Leong (Berkeley, CA); Andrew Polson (San Francisco, CA); Paul Polakis (Mill Valley, CA); Yan Wu (Foster City, CA); Wei-Ching Liang (Foster City, CA); Ron Firestein (Burlingame, CA)
Assignee:
Genentech, Inc.
C07K16/2827A61K31/404A61K31/5517A61K31/706A61K38/05A61K47/68031A61K47/68035A61K47/6809A61K47/6855A61K47/6869C07K16/3015C07K16/3069G01N33/57492A61K2039/505C07K2317/21C07K2317/24C07K2317/31C07K2317/33C07K2317/565C07K2317/567C07K2317/73C07K2317/77C07K2317/92
View Patent ↗
Loading inventors, assignments & file history…
Abstract
The invention provides anti-B7-H4 antibodies and immunoconjugates and methods of using the same.
Claims (28)
1. Isolated nucleic acid encoding
an antibody that binds to B7-H4, wherein the antibody comprises:
(a) (i) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 39, (ii) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 40, and (iii) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 128, (iv) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 42, (v) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 43, and (vi) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 129; or
(b) (i) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 39, (ii) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 40, and (iii) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 41, (iv) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 42, (v) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 43, and (vi) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 129.
2. A host cell comprising the nucleic acid of claim 1 .
3. A method of producing an antibody comprising culturing the host cell of claim 1 so that the antibody is produced.
4. The method of claim 3 , further comprising isolating the antibody.
5. The isolated nucleic acid of claim 1 , wherein the antibody further comprises a heavy chain framework FR3 sequence of SEQ ID NO: 53.
6. The isolated nucleic acid of claim 1 , wherein the antibody comprises a light chain framework FR3 sequence of SEQ ID NO: 47.
7. The isolated nucleic acid of claim 1 , wherein the antibody comprises:
(a) a VH sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 38;
(b) a VL sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 126; or
(c) a VH sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 127; or
(d) a VH sequence as in (a) and a VL sequence as in (b); or
(e) a VH sequence as in (c) and a VL sequence as in (b).
8. The isolated nucleic acid of claim 1 , wherein the antibody comprises a VH sequence of SEQ ID NO: 38 or 127.
9. The isolated nucleic acid of claim 1 , wherein the antibody comprises a VL sequence of SEQ ID NO: 126.
10. The isolated nucleic acid of claim 1 , wherein the antibody comprises: (a) a VH sequence of SEQ ID NO: 38 and a VL sequence of SEQ ID NO: 126; or (b) a VH sequence of SEQ ID NO: 127 and a VL sequence of SEQ ID NO: 126.
11. The isolated nucleic acid of claim 1 , wherein the antibody is a humanized or chimeric antibody.
12. The isolated nucleic acid of claim 1 , wherein the antibody is an antibody fragment that binds B7-H4.
13. The isolated nucleic acid of claim 1 , wherein the antibody is an IgG1, IgG2a or IgG2b antibody.
14. The isolated nucleic acid of claim 1 , wherein the antibody comprises one or more engineered cysteine amino acids residues.
15. The isolated nucleic acid of claim 14 , wherein the one or more engineered cysteine amino acid residues is located in the light chain.
16. The isolated nucleic acid of claim 15 , wherein the antibody comprises at least one mutation in the light chain constant region selected from K149C and V205C.
17. The isolated nucleic acid of claim 14 , wherein the one or more engineered cysteine amino acid residues is located in the heavy chain.
18. The isolated nucleic acid of claim 17 , wherein the antibody comprises at least one mutation in the heavy chain constant region selected from A118C and S400C.
19. The isolated nucleic acid of claim 1 , wherein the antibody comprises (a) a heavy chain sequence of SEQ ID NO: 132 and a light chain sequence of SEQ ID NO: 134; or (b) a heavy chain sequence of SEQ ID NO: 130 and a light chain sequence of SEQ ID NO: 140; or (c) a heavy chain sequence of SEQ ID NO: 130 and a light chain sequence of SEQ ID NO: 141; or (d) a heavy chain sequence of SEQ ID NO: 130 and a light chain sequence of SEQ ID NO: 145; or (e) a heavy chain sequence of SEQ ID NO: 130 and a light chain sequence of SEQ ID NO: 146.
20. The isolated nucleic acid of claim 1 , wherein is the antibody binds human B7-H4 of SEQ ID NO: 73.
Continuity (4)
Provisional Application
62049701
· Sep 12, 2014
References Cited (371)
US 3896111A
· Kupchan et al.
· 1975
[cited by applicant]
US 4137230A
· Hashimoto et al.
· 1979
[cited by applicant]
US 4151042A
· Higashide et al.
· 1979
[cited by applicant]
US 4248870A
· Miyashita et al.
· 1981
[cited by applicant]
US 4256746A
· Miyashita et al.
· 1981
[cited by applicant]
US 4260608A
· Miyashita et al.
· 1981
[cited by applicant]
US 4265814A
· Hashimoto et al.
· 1981
[cited by applicant]
US 4294757A
· Asai
· 1981
[cited by applicant]
US 4307016A
· Asai et al.
· 1981
[cited by applicant]
US 4308268A
· Miyashita et al.
· 1981
[cited by applicant]
US 4308269A
· Miyashita et al.
· 1981
[cited by applicant]
US 4309428A
· Miyashita et al.
· 1982
[cited by applicant]
US 4313946A
· Powell et al.
· 1982
[cited by applicant]
US 4315929A
· Freedman et al.
· 1982
[cited by applicant]
US 4317821A
· Miyashita et al.
· 1982
[cited by applicant]
US 4322348A
· Asai et al.
· 1982
[cited by applicant]
US 4331598A
· Hasegawa et al.
· 1982
[cited by applicant]
US 4361650A
· Asai et al.
· 1982
[cited by applicant]
US 4362663A
· Kida et al.
· 1982
[cited by applicant]
US 4364866A
· Asai et al.
· 1982
[cited by applicant]
US 4371533A
· Akimoto et al.
· 1983
[cited by applicant]
US 4424219A
· Hashimoto et al.
· 1984
[cited by applicant]
US 4450254A
· Isley et al.
· 1984
[cited by applicant]
US 4676980A
· Segal et al.
· 1987
[cited by applicant]
US 4816567A
· Cabilly et al.
· 1989
[cited by applicant]
US 5208020A
· Chari et al.
· 1993
[cited by applicant]
US 5362852A
· Geoghegan
· 1994
[cited by applicant]
US 5416064A
· Chari et al.
· 1995
[cited by applicant]
US 5500362A
· Robinson et al.
· 1996
[cited by applicant]
US 5571894A
· Wels et al.
· 1996
[cited by applicant]
US 5587458A
· King et al.
· 1996
[cited by applicant]
US 5624821A
· Winter et al.
· 1997
[cited by applicant]
US 5635483A
· Pettit et al.
· 1997
[cited by applicant]
US 5648237A
· Carter
· 1997
[cited by applicant]
US 5648260A
· Winter et al.
· 1997
[cited by applicant]
US 5663149A
· Pettit et al.
· 1997
[cited by applicant]
US 5712374A
· Kuntsmann et al.
· 1998
[cited by applicant]
US 5714586A
· Kunstmann et al.
· 1998
[cited by applicant]
US 5731168A
· Carter et al.
· 1998
[cited by applicant]
US 5739116A
· Hamann et al.
· 1998
[cited by applicant]
US 5750373A
· Garrard et al.
· 1998
[cited by applicant]
US 5767237A
· Sakakibara et al.
· 1998
[cited by applicant]
US 5767285A
· Hamann et al.
· 1998
[cited by applicant]
US 5770429A
· Lonberg et al.
· 1998
[cited by applicant]
US 5780588A
· Pettit et al.
· 1998
[cited by applicant]
US 5789199A
· Joly et al.
· 1998
[cited by applicant]
US 5821337A
· Carter et al.
· 1998
[cited by applicant]
US 5840523A
· Simmons et al.
· 1998
[cited by applicant]
US 5869046A
· Presta et al.
· 1999
[cited by applicant]
US 5959177A
· Hein et al.
· 1999
[cited by applicant]
US 6040498A
· Stomp et al.
· 2000
[cited by applicant]
US 6075181A
· Kucherlapati et al.
· 2000
[cited by applicant]
US 6124431A
· Sakakibara et al.
· 2000
[cited by applicant]
US 6150584A
· Kucherlapati et al.
· 2000
[cited by applicant]
US 6171586B1
· Lam et al.
· 2001
[cited by applicant]
US 6194551B1
· Idusogie et al.
· 2001
[cited by applicant]
US 6214345B1
· Firestone et al.
· 2001
[cited by applicant]
US 6248516B1
· Winter et al.
· 2001
[cited by applicant]
US 6267958B1
· Andya et al.
· 2001
[cited by applicant]
US 6333410B1
· Chari et al.
· 2001
[cited by applicant]
US 6417429B1
· Hein et al.
· 2002
[cited by applicant]
US 6420548B1
· Vezina et al.
· 2002
[cited by applicant]
US 6441163B1
· Chari et al.
· 2002
[cited by applicant]
US 6602684B1
· Umana et al.
· 2003
[cited by applicant]
US 6630579B2
· Chari et al.
· 2003
[cited by applicant]
US 6737056B1
· Presta
· 2004
[cited by applicant]
US 6884799B2
· Kamal et al.
· 2005
[cited by applicant]
US 6913748B2
· Widdison
· 2005
[cited by applicant]
US 6982321B2
· Winter
· 2006
[cited by applicant]
US 7041870B2
· Tomizuka et al.
· 2006
[cited by applicant]
US 7049311B1
· Thurston et al.
· 2006
[cited by applicant]
US RE39151E
· Chari et al.
· 2006
[cited by applicant]
US 7067511B2
· Thurston et al.
· 2006
[cited by applicant]
US 7087409B2
· Barbas et al.
· 2006
[cited by applicant]
US 7125978B1
· Vezina et al.
· 2006
[cited by applicant]
US 7265105B2
· Thurston et al.
· 2007
[cited by applicant]
US 7276497B2
· Chari et al.
· 2007
[cited by applicant]
US 7332581B2
· Presta
· 2008
[cited by applicant]
US 7371826B2
· Presta
· 2008
[cited by applicant]
US 7375078B2
· Feng
· 2008
[cited by applicant]
US 7498298B2
· Doronina et al.
· 2009
[cited by applicant]
US 7511032B2
· Liu et al.
· 2009
[cited by applicant]
US 7521541B2
· Eigenbrot et al.
· 2009
[cited by applicant]
US 7527791B2
· Adams et al.
· 2009
[cited by applicant]
US 7528126B2
· Howard et al.
· 2009
[cited by applicant]
US 7557099B2
· Howard et al.
· 2009
[cited by applicant]
US 7619068B2
· Pilkington et al.
· 2009
[cited by applicant]
US 7659241B2
· Senter et al.
· 2010
[cited by applicant]
US 9562099B2
· Leong et al.
· 2017
[cited by applicant]
US 20030157108A1
· Presta
· 2003
[cited by applicant]
US 20040093621A1
· Shitara et al.
· 2004
[cited by applicant]
US 20040110704A1
· Yamane et al.
· 2004
[cited by applicant]
US 20040132140A1
· Satoh et al.
· 2004
[cited by applicant]
US 20050079574A1
· Bond
· 2005
[cited by applicant]
US 20050163772A1
· Dong et al.
· 2005
[cited by applicant]
US 20050276812A1
· Ebens et al.
· 2005
[cited by applicant]
US 20060025576A1
· Miller et al.
· 2006
[cited by applicant]
US 20060104968A1
· Bookbinder et al.
· 2006
[cited by applicant]
US 20070117126A1
· Sidhu et al.
· 2007
[cited by applicant]
US 20070237764A1
· Birtalan et al.
· 2007
[cited by applicant]
US 20070292936A1
· Barthelemy et al.
· 2007
[cited by applicant]
US 20090136490A1
· Pilkington et al.
· 2009
[cited by applicant]
US 20110256157A1
· Howard et al.
· 2011
[cited by applicant]
US 20160146806A1
· Langermann et al.
· 2016
[cited by applicant]
US 20170239366A1
· Leong et al.
· 2017
[cited by applicant]
CN 0404097B1
· 1996
[cited by applicant]
CN 10544697
· 2009
[cited by applicant]
CN 103981150
· 2014
[cited by applicant]
WO 8101145A1
· 1981
[cited by applicant]
WO 0328147
· 1989
[cited by applicant]
WO 9301161A1
· 1993
[cited by applicant]
WO 9308829A1
· 1993
[cited by applicant]
WO 9316185A2
· 1993
[cited by applicant]
WO 9321232A1
· 1993
[cited by applicant]
WO 9411026A2
· 1994
[cited by applicant]
WO 9411026a3
· 1994
[cited by applicant]
WO 9429351A2
· 1994
[cited by applicant]
WO 0425235B1
· 1996
[cited by applicant]
WO 9730087A1
· 1997
[cited by applicant]
WO 9858964A1
· 1998
[cited by applicant]
WO 9922764
· 1999
[cited by applicant]
WO 9951642A1
· 1999
[cited by applicant]
WO 2004010957
· 2000
[cited by applicant]
WO 2000012507
· 2000
[cited by applicant]
WO 200061739
· 2000
[cited by applicant]
WO 0129246A1
· 2001
[cited by applicant]
WO 02031140A1
· 2002
[cited by applicant]
WO 02088172A2
· 2002
[cited by applicant]
WO 02088172A3
· 2002
[cited by applicant]
WO 02088172R1
· 2002
[cited by applicant]
WO 03011878A2
· 2003
[cited by applicant]
WO 2003026577
· 2003
[cited by applicant]
WO 2003043583
· 2003
[cited by applicant]
WO 03084570A1
· 2003
[cited by applicant]
WO 03085107A1
· 2003
[cited by applicant]
WO 03085119A1
· 2003
[cited by applicant]
WO 2004032828A2
· 2004
[cited by applicant]
WO 2004056312A2
· 2004
[cited by applicant]
WO 2004101756A2
· 2004
[cited by applicant]
WO 2005023814A1
· 2005
[cited by applicant]
WO 2005035586a1
· 2005
[cited by applicant]
WO 2005035778A1
· 2005
[cited by applicant]
WO 2005053742A1
· 2005
[cited by applicant]
WO 2005100402A1
· 2005
[cited by applicant]
WO 2006029879A2
· 2006
[cited by applicant]
WO 2006029879A3
· 2006
[cited by applicant]
WO 2006044908A2
· 2006
[cited by applicant]
WO 2006053110A2
· 2006
[cited by applicant]
WO 2007008603A1
· 2007
[cited by applicant]
WO 2007008848A2
· 2007
[cited by applicant]
WO 2007008848A3
· 2007
[cited by applicant]
WO 2008067283A2
· 2008
[cited by applicant]
WO 2008077546A1
· 2008
[cited by applicant]
WO 2009016516A2
· 2009
[cited by applicant]
WO 2009073533A2
· 2009
[cited by applicant]
WO 2009089004A1
· 2009
[cited by applicant]
WO 2009099741A1
· 2009
[cited by applicant]
WO 2010009124
· 2010
[cited by applicant]
WO 2011056983A1
· 2011
[cited by applicant]
WO 2011130598
· 2011
[cited by applicant]
WO 2013025779A1
· 2013
[cited by applicant]
WO 2013149159A1
· 2013
[cited by applicant]
WO 2014100483
· 2014
[cited by applicant]
WO 2014159835A1
· 2014
[cited by applicant]
Abdiche et al., “Assessing kinetic and epitopic diversity across orthogonal monoclonal antibody generation platforms,” MAbs. 8(2): 264-77 (2016).
[cited by applicant]
Ajani et al., “A Multi-Institutional Phase II Study of BMS-182248-01 (BR96-Doxorubicin Conjugate) Administered Every 21 Days in Patients with Advanced Gastric Adenocarcinoma” Cancer Journal 6:78-81 ( 2000).
[cited by applicant]
Alley, S.C. et al., “Controlling the location of drug attachment in antibody-drug conjugates, Abstract No. 627, American Association for Cancer Research, 2004 Annual Meeting, Mar. 27-31, 2004 Proceedings of the AACR” 45…
[cited by applicant]
Almagro et al., “Humanization of antibodies” Frontiers in Bioscience 13:1619-1633 (Jan. 2008).
[cited by applicant]
Amsberry and Borchardt, “The Lactonization of 2'-Hydroxy Hydrocinnamic Acid Amides: A Potential Prodrugs for Amines” J. Org. Chem 55(23):5867-5877 ( 1990).
[cited by applicant]
Antonow et al., “Structure-Activity Relationships of Monomeric C2-Aryl Pyrrolo[2,1-c][1,4]benzodiazepine (PBD) Antitumor Agents” J Med Chem(53):2927-2941 ( 2010).
[cited by applicant]
Baca et al., “Antibody humanization using monovalent phage display” J Biol Chem 272(16):10678-10684 ( 1997).
[cited by applicant]
Boerner et al., “Production of Antigen-Specific Human Monoclonal Antibodies From In Vitro-Primed Human Splenocytes” J Immunol 147(1):86-95 (Jul. 1991).
[cited by applicant]
Boyd et al., “Deep sequencing and human antibody repertoire analysis,” Current Opinion in Immunology 40: 103-109 (2016).
[cited by applicant]
Brennan et al., “Preparation of Biospecific Antibodies By Chemical Recombination of Monoclonal Immunoglobulin G1 Fragments” Science 229(4708):81-83 (Jul. 5, 1985).
[cited by applicant]
Bruggemann et al., “Comparison of the Effector Functions of Human Immunogobulins Using a Matched set of Chimeric Antibodies” Journal Exp. Med. 166:1351-1361 ( 1987).
[cited by applicant]
Bubendorf et al., “Tissue microarray (TMA) technology: miniaturized pathology archives for high-throughput in situ studies” J Pathol 195:72-79 ( 2001).
[cited by applicant]
Carter and Senter, “Antibody-drug Conjugates for Cancer Therapy” Cancer J. 14:154-169 (2008).
[cited by applicant]
Carter et al., “Humanization of an anti-p185 HER2 antibody for human cancer therapy” P Natl Acad Sci USA 89:4285-4289 (May 1992).
[cited by applicant]
Chari et al., “Immunoconjugates Containing Novel Maytansinoids: Promising Anticancer Drugs” Cancer Research 52:127-131 ( 1992).
[cited by applicant]
Chari, “Targeted Cancer Therapy: Conferring Specificity to Cytotoxic Drugs” Accounts of Chemical Research 41(1):98-107 ( 2008).
[cited by applicant]
Chen et al., “Selection and analysis of an optimized anti-VEGF antibody: crystal structure of an affinity-matured Fab in complex with antigen” J Mol Biol 293(4):865-881 (Nov. 5, 1999).
[cited by applicant]
Choi et al., “Genomic organization and expression analysis of B7-H4, an immune inhibitory molecule of the B7 family” J Immunol 171(9):4650-4654 (Nov. 1, 2003).
[cited by applicant]
Chothia et al., “Canonical structures for the hypervariable regions of immunoglobulins” J Mol Biol 196:901-917 ( 1987).
[cited by applicant]
Chowdhury, “Engineering hot spots for affinity enhancement of antibodies” Methods Molec Biol 207:179-196 ( 2008).
[cited by applicant]
Clackson et al., “Making antibody fragments using phage display libraries” Nature 352:624-628 (Aug. 15, 1991).
[cited by applicant]
Clynes et al., “Fc receptors are required in passive and active immunity to melanoma” P Natl Acad Sci USA 95(2):652-656 (Jan. 1998).
[cited by applicant]
Conroy et al., “Antibodies: From novel repertoires to defining and refining the structure of biologically important targets,” Methods. 1 (116): 12-22 (2017).
[cited by applicant]
Cragg et al., “Antibody Specificity Controls in Vivo Effector Mechanisms of Anti-CD20 Regents” Blood 103:2738-2743 ( 2004).
[cited by applicant]
Cragg, M.S. et al., “Complement-Mediated Lysis by Anti-CD20 mAb Correlates with Segregation into Lipid Rafts” Blood 101(3):1045-1051 (2003).
[cited by applicant]
Cree et al., “Methotrexate chemosensitivity by ATP luminescence in human leukemia cell lines and in breast cancer primary cultures: comparison of the TCA-100 assay with a clonogenic assay” Anticancer Drugs 6:398-404 ( 1…
[cited by applicant]
Crouch et al., “The use of ATP bioluminescence as a measure of cell proliferation and cytotoxicity” J. Immunol Methods 160:81-88 ( 1993).
[cited by applicant]
Cunningham and Wells, “High-resolution epitope mapping of hGH-receptor interactions by alanine-scanning mutagenesis” Science 24:1081-1085 (Jun. 2, 1989).
[cited by applicant]
Dall'Acqua et al., “Antibody humanization by framework shuffling” Methods 36(1):43-60 (Jan. 17, 2005).
[cited by applicant]
Doronina et al., “Development of potent monoclonal antibody auristatin conjugates for cancer therapy” Nat Biotechnol 21(7):778-784 (Jul. 2003).
[cited by applicant]
Doronina et al., “Enhanced activity of monomethylauristatin F through monoclonal antibody delivery: effects of linker technology on efficacy and toxicity” Bioconjug Chem 17(1):114-124 (Jan. 2006).
[cited by applicant]
Dubowchik and Radia, “Monomethoxytrityl (MMT) as a Versatile Amino Protecting Group for Complex Prodrugs on Anticancer Compounds Sensitive to Strong Acids, Bases and Nucleophiles” Tetrahedron Lett 38(30):5257-5260 ( 199…
[cited by applicant]
Dubowchik et al., “Doxorubicin immunoconjugates containing bivalent, lysosomally-cleavable dipeptide linkages” Bioorg Med Chem Lett 12:1529-1532 ( 2002).
[cited by applicant]
Duncan and Winter, “The Binding Site for Clq on IgG” Nature 332:738-740 (Apr. 21, 1988).
[cited by applicant]
Fellouse et al., “Synthetic antibodies from a four-amino-acid code: A dominant role for tyrosine in antigen recognition” P Natl Acad Sci USA 101(34):12467-12472 (Aug. 24, 2004).
[cited by applicant]
Ferrara et al., “Recombinant renewable polyclonal antibodies,” mAbs 7: 32-41 (2015).
[cited by applicant]
File history for U.S. Appl. No. 14/207,878, filed Mar. 13, 2014.
[cited by applicant]
File history for U.S. Appl. No. 14/773,334.
[cited by applicant]
File history for U.S. Appl. No. 15/386,577, filed Dec. 21, 2016.
[cited by applicant]
File history for U.S. Appl. No. 16/167,000, filed Oct. 22, 2018.
[cited by applicant]
File history for U.S. Appl. No. 17/547,528, filed Dec. 10, 2021.
[cited by applicant]
Flatman et al., “Process analytics for purification of monoclonal antibodies” Journal of Chromatography B 848:79-87 ( 2007).
[cited by applicant]
Foote et al., “Antibody Framework Residues Affecting the Conformation of the Hypervariable Loops” J Mol Biol 224:487-499 ( 1992).
[cited by applicant]
Fraker and Speck, “Protein and Cell Membrane Iodinations with a Sparingly Soluble Chloroamide, 1, 3, 4, 6-Tetrachloro-3a, 6a-Diphenylglycoluril” Biochem Biophysic Res Commun 80(4) (Feb. 28, 1978).
[cited by applicant]
Francisco et al., “cAC10-vcMMAE, an anti-CD30-monomethly auristatin E conjugate with potent and selective antitumor activity” Blood 102(4):1458-1465 (Aug. 15, 2003).
[cited by applicant]
Frisch et al., “Synthesis of Short Polyoxyethlene-Based Heterobifunctional Cross-Linking Reagents. Application to the Coupling of Peptides to Liposomes” Bioconjugate Chem 7(2):180-186 (Feb. 1, 1996).
[cited by applicant]
Gazzano-Santoro et al., “A non-radioactive complement-dependent cytotoxicity assay for anti-CD20 monoclonal antibody” J Immunol Methods 202:163-171 ( 1997).
[cited by applicant]
Geoghegan and Stroh, “Site-directed conjugation of nonpeptide groups to peptides and proteins via periodate oxidation of a 2-amino alcohol. Application to modification at N-terminal serine” Bioconjugate Chem. 3:138-146 …
[cited by applicant]
Gerngross, “Advances in the Production of Human Therapeutic Proteins in Yeasts and Filamentous Fungi” Nat. Biotech. 22:1409-1414 ( 2004).
[cited by applicant]
Graham et al., “Characteristics of a Human Cell Line Transformed by DNA form Human Adenovirus Type 5” J. Gen. Virol. 36:59 ( 1977).
[cited by applicant]
Grandi et al., “Novel anthracycline analogs” Cancer Treatment Reviews 17:133-138 ( 1990).
[cited by applicant]
Griffiths et al., “Human anti-self antibodies with high specificity from phage display libraries” Embo J 12(2):725-734 (Feb. 1993).
[cited by applicant]
Gruber et al., “Efficient tumor cell lysis mediated by a bispecific single chain antibody expressed in
[cited by applicant]
Guyer et al., “Immunoglobulin binding by mouse intestinal epithelial cell receptors” J Immunol 117(2):587-593 (Aug. 1976).
[cited by applicant]
Hamann, “Monoclonal antibody—drug conjugates” Expert Opin Ther Patents 15(9):1087-1103 ( 2005).
[cited by applicant]
Hamblett et al., (‘Effect of drug loading on the pharmacology, pharmacokinetics and toxicity of an anti-CD30 antibody-drug conjugate, Abstract No. 624, American Association for Cancer Research; 2004 Annual Meeting, Mar.…
[cited by applicant]
Hamblett et al., “Effects of drug loading on the antitumor activity of a monoclonal antibody drug conjugate” Clin Cancer Res 10:7063-7070 ( 2004).
[cited by applicant]
Hartley et al., “SG2285, a novel C2-aryl-substituted pyrrolobenzodiazepine dimer prodrug that cross-links DNA and exerts highly potent antitumor activity” Cancer Res. 70(17):6849-6858 ( 2010).
[cited by applicant]
Hay et al. et al., “A 2-Nitroimidazole Carbamate Produrg of 5-Amino-1-(Chloromethyl)-3-[(5,6, 7-Trimethoxyindol-2-YL) Carbonyl]-1,2-Dihydro-3H-Benz[E]Indole (Amino-Seco-CBI-TMI) for use with Adept and Gdept” Bioorg Med …
[cited by applicant]
He et al., “Research Progress of B7-H4,” J. Chronic Pathemathol. 14(2):123-126 (2013).
[cited by applicant]
Hellstrom et al., “Antitumor effects of L6, an IgG2a antibody that reacts with most human carcinomas” P Natl Acad Sci USA 83:7059-7063 (Sep. 1986).
[cited by applicant]
Hellstrom et al., “Strong antitumor activities of IgG3 antibodies to a human melanoma-associated ganglioside” P Natl Acad Sci USA 82:1499-1502 (Mar. 1985).
[cited by applicant]
Hinman et al., “Preparation and characterization of monoclonal antibody conjugates of the calicheamicins: A novel and potent family of antitumor antibiotics” Cancer Res 53:3336-3342 ( 1993).
[cited by applicant]
Hollinger et al., Proceedings of the National Academy of Sciences 90:6444-6448 (Jul. 1993).
[cited by applicant]
Holmes et al., “Identification of Heregulin, A Specific Activator of p185
[cited by applicant]
Hoogenboom et al., “By-passing immunisation. Human antibodies from synthetic repertoires of germline VH gene segments rearranged in vitro” J Mol Biol 227(2):381-388 (Sep. 1992).
[cited by applicant]
Hoogenboom et al., “Overview of antibody phage-display technology and its applications” Methods Mol Biol 178:1-37 ( 2002).
[cited by applicant]
Howard et al., “Synthesis of a novel C2/C2′-aryl-substituted pyrrolo[2,1-c][1,4]benzodiazepine dimer prodrug with improved water solubility and reduced DNA reaction rate” Bioorg Med Chem Lett 19(22):6463-6466 ( 2009).
[cited by applicant]
Hudson et al., “Engineered antibodies” Nature Medicine 9(1):129-134 (Jan. 2003).
[cited by applicant]
Hurley et al., “Covalent Binding of Antitumor Antibiotics in the Minor Groove of DNA. Mechanism of Action of CC-1065 and the Pyrrolo(1,4)benzodiazepines” Acc Chem Res 19:230-237 ( 1986).
[cited by applicant]
Idusogie et al., “Mapping of the C1q Binding Site on Rituxan, A Chimeric Antibody with a Human IgG1 Fc” J Immunol 164(8):4178-4184 ( 2000).
[cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2014/025285 filed Mar. 13, 2014, pp. 13 (mailed Jun. 26, 2014).
[cited by applicant]
International Search Report and Written Opinion for PCT Application No. PCT/US2015/049551, pp. 21 (mailed Feb. 16, 2016).
[cited by applicant]
Jeffrey et al., “Dipeptide-based highly potent doxorubicin antibody conjugates” Bioorganic & Medicinal Chemistry Letters 16:358-362 ( 2006).
[cited by applicant]
Kam et al., “Carbon nanotubes as multifunctional biological transporters and near-infrared agents for selective cancer cell destruction” PNAS 102(33):11600-11605 (Aug. 16, 2005).
[cited by applicant]
Kanda et al., “Comparison of cell lines for stable production of fucose-negative antibodies with enhanced ADCC” Biotechnol Bioeng 94(4):680-688 (Jul. 5, 2006).
[cited by applicant]
Kashmiri et al., “SDR grafting—a new approach to antibody humanization” Methods 36:25-34 ( 2005).
[cited by applicant]
Khan et al. “Cross-neutralizing anti-HIV-1 human single chain variable fragments(scFvs) against CD4 binding site and N332 glycan identified from a recombinant phage library,” Sci Rep 7: 45163 (2017). https://doi.org/10.…
[cited by applicant]
Kim et al., “Localization of the site of the murine IgGI molecule that is involved in binding to the murine intestinal Fc receptor” Eur J Immunol 24:2429-2434 ( 1994).
[cited by applicant]
Kinet et al., “Fc receptors” Annu Rev Immunol. 9:457-92 ( 1991).
[cited by applicant]
King et al., “Monoclonal antibody conjugates of doxorubicin prepared with branched peptide linkers: Inhibition of aggregation by methoxytriethyleneglycol chains” Journal of Medical Chemistry 45:4336-4343 ( 2002).
[cited by applicant]
Kingsbury et al., “A Novel Peptide Delivery System Involving Peptidase Activated Prodrugs as Antimicrobial Agents. Synthesis and Biological Activity of Peptidyl Derivatives of 5-Fluorouracil” J. Med. Chem. 27(11):1447-1…
[cited by applicant]
Klimka et al., “Human anti-CD30 recombinant antibodies by guided phage antibody selection using cell panning” Brit J Cancer 83(2):252-260 ( 2000).
[cited by applicant]
Klussman et al., “Secondary mAb-vcMMAE Conjugates Are Highly Sensitive REporters of Antibody Internalization via the Lysosome Pathway” Bioconjugate Chem. 15(4):765-773 (Jun. 18, 2004).
[cited by applicant]
Konitzer et al., “Generation of a highly diverse panel of antagonistic chicken monoclonal antibodies against the GIP receptor,” mAbs 9:536-549 (2017).
[cited by applicant]
Kostelny et al., “Formation of a bispecific antibody by the use of leucine zippers” J Immunol. 148:1547-1553 (Mar. 1, 1992).
[cited by applicant]
Kozbor et al., “A Human Hybrid Myeloma for Production of Human Monoclonal Antibodies” J Immunol 133(6):3001-3005 (Dec. 1, 1984).
[cited by applicant]
Kratz et al., “Prodrugs of anthracyclines in cancer chemotherapy” Curr Med Chem 13:477-523 ( 2006).
[cited by applicant]
Lee et al., “Bivalent antibody phage display mimics natural immunoglobulin” J Immunol Methods 284(1-2):119-132 ( 2004).
[cited by applicant]
Lee et al., “High-affinity human antibodies from phage-displayed synthetic Fab libraries with a single framework scaffold” J Mol Biol 340(5):1073-1093 ( 2004).
[cited by applicant]
Lee et al., “Molecular-level analysis of the serum antibody repertoire in young adults before and after seasonal influenza vaccination,” Nat Med. 22(12): 1456-1464 (2016).
[cited by applicant]
Leimgruber et al., “Isolation and characterization of anthramycin, a new antitumor antibiotic” J Am Chem Soc 87(24):5791-5793 ( 1965).
[cited by applicant]
Leimgruber et al., “The structure of anthramycin” J Am Chem Soc 87(24):5793-5795 ( 1965).
[cited by applicant]
Leong et al., “An anti-B7-H4 antibody-drug conjugate for the treatment of breast cancer” Molecular Pharmaceutics 12(6):1717-1729 (Apr. 8, 2015).
[cited by applicant]
Li et al., “Human antibodies for immunotherapy development generated via a human B cell hybridoma technology” P Natl Acad Sci USA 103(10):3557-62 (Mar. 2006).
[cited by applicant]
Li et al., “Optimization of humanized IgGs in glycoengineered Pichia pastoris” Nat Biotechnol 24(2):210-215 (Feb. 2006).
[cited by applicant]
Liu et al. et al., “Eradication of large colon tumor xenografts by targeted delivery of maytansinoids” P Natl Acad Sci USA 93(16):8618-8623 (Aug. 6, 1996).
[cited by applicant]
Lode et al., “Targeted therapy with a novel enediyene antibiotic calicheamicin V11 effectively suppresses growth and dissemination of liver metastases in a syngeneic model of murine neuroblastoma” Cancer Res 58:2925-292…
[cited by applicant]
Lonberg, “Fully human antibodies from transgenic mouse and phage display platforms” Current Opin Immunol 20:450-459 ( 2008).
[cited by applicant]
Lonberg, N., “Human antibodies from transgenic animals” Nat Biotechnol 23(9):1117-11125 ( 2005).
[cited by applicant]
Lyon et al., “Conjugation of anticancer drugs through endogenous monoclonal antibody cysteine residues” Methods Enzymol 502:123-138 ( 2012).
[cited by applicant]
Maccallum et al., “Antibody-antigen interactions: contact analysis and binding site topography” J Mol Biol 262(5):732-745 (Oct. 11, 1996).
[cited by applicant]
Mandler et al., “Immunoconjugates of geldanamycin and Anti-HER2 monoclonal antibodies: antiproliferative activity on human breast carcinoma cell lines” J National Cancer Institute 92(19):1573-1581 (Oct. 4, 2000).
[cited by applicant]
Mandler et al., “Modifications in synthesis strategy improve the yield and efficacy of geldanamycin—herceptin immunoconjugates” Bioconjugate Chem 13:786-791 ( 2002).
[cited by applicant]
Mandler et al., “Synthesis and evaluation of antiproliferative activity of a Geldanamycin-Herceptin™ immunoconjugate” Bioorg Med Chem Lett 10:1025-1028 ( 2000).
[cited by applicant]
Marks et al., “By-passing immunization, human antibodies from V-gene libraries displayed on phage” J Mol Biol 222:581-597 ( 1991).
[cited by applicant]
Marks et al., “Selection of Human Antibodies from Phage Display Libraries” Methods in Molecular Biology 248:161-176 ( 2003).
[cited by applicant]
Mather et al., “Culture of testicular cells in hormone—supplemented serum-free medium” Ann Ny Acad Sci 383:44-68 ( 1982).
[cited by applicant]
Mather, “Establishment and characterization of two distinct mouse testicular epithelial cell lines” Biol Reprod 23:243-252 ( 1980).
[cited by applicant]
McCafferty et al., “Phage Antibodies: Filamentous Phage Displaying Antibody Variable Domains” Nature 348:552-554 (Dec. 1990).
[cited by applicant]
McDonagh et al., “Engineered antibody-drug conjugates with defined sites and stoichiometries of drug attachment” Protein Engineering, Design & Selection 19(7):299-307 (Apr. 28, 2006).
[cited by applicant]
Milstein and Cuello, “Hybrid hybridomas and their use in immunohistochemistry” Nature 305:537-540 (Oct. 6, 1983).
[cited by applicant]
Morrison et al., “Chimeric human antibody molecules: Mouse antigen-binding domains with human constant region domains” P Natl Acad Sci USA 81:6851-6855 (Nov. 1984).
[cited by applicant]
Nagy et al., “Stability of cytotoxic luteinizing hormone-releasing hormone conjugate (AN-152) containing doxorubicin 14-O-hemiglutarate in mouse and human serum in vitro: implications for the design of preclinical studi…
[cited by applicant]
Neuberger et al., “Recombinant Antibodies Possessing Novel Effector Functions” Nature 312:604-608 (Dec. 13, 1984).
[cited by applicant]
Okazaki et al., “Fucose depletion from human IgG1 oligosaccharide enhances binding enthalpy and association rate between IgG1 and FcgammaRIIIa” J Mol Biol 336(5):1239-1249 (Mar. 5, 2004).
[cited by applicant]
Osbourn et al., “From rodent reagents to human therapeutics using antibody guided selection” Methods 36:61-68 ( 2005).
[cited by applicant]
Pacciarini et al., “Phase I/II trial of nemorubicin hydrochloride in combination with cisplatin is supported by new preclinical evidences of its mechanism of action” J Clin Oncol (Abstract from 2006 ASCO Annual Meeting …
[cited by applicant]
Padlan, “A possible procedure for reducing the immunogenicity of antibody variable domains while preserving their ligand-binding properties” Mol Immunol 28(4/4):489-498 ( 1991).
[cited by applicant]
Parola et al., “Integrating high-throughput screening and sequencing for monoclonal antibody discovery and engineering,” Immunology. 153(1): 31-41 (2018).
[cited by applicant]
Petkova et al., “Enhanced half-life of genetically engineered human IgG1 antibodies in a humanized FcRn mouse model: potential application in humorally mediated autoimmune disease” Int Immunol 18(12):1759-69 (Dec. 2006).
[cited by applicant]
Pettit et al., “Antineoplastic agents 365. Dolastatin 10 SAR probes” Anti-Cancer Drug Design 13:243-277 ( 1998).
[cited by applicant]
Pettit et al., “Dolastatins 24: synthesis of (−)-dolastatin 10
[cited by applicant]
Pettit et al., “Specific activities of dolastatin 10 and peptide derivatives against Cryptococcus neoformans” Antimicrob. Agents Chemother. 42(11):2961-2965 (Nov. 1985).
[cited by applicant]
Pettit et al., “The absolute configuration and synthesis of natural (−)-Dolastatin 10
[cited by applicant]
Pettit et al., “The dolastatins; 18: stereospecific synthesis of dolaproine” Synthesis:719-725 (Jun. 1996).
[cited by applicant]
Polakis, “Arming antibodies for cancer therapy” Curr Opin Pharm 5:382-387 ( 2005).
[cited by applicant]
Portolano et al., “Lack of promiscuity in autoantigen-specific H and L chain combinations as revealed by human H and L chain 'roulette” J Immunol 150(3):880-7 (Feb. 1, 1993).
[cited by applicant]
Presta et al., “Humanization of an Antibody Directed Against IgE” J Immunol 151(5):2623-2632 (Sep. 1, 1993).
[cited by applicant]
Presta et al., “Humanization of an Anti-Vascular Endothelial Growth Factor Monoclonal Antibody for the Therapy of Solid Tumors and Other Disorders” Cancer Res 57(20):4593-4599 (Oct. 15, 1997).
[cited by applicant]
Queen et al., “A humanized Antibody that Binds to the Interleukin 2 Receptor” P.N.A.S. USA 86:10029-10033 ( 1989).
[cited by applicant]
Quintieri et al., “Formation and antitumor activity of PNU-159682, a major metabolite of nemorubicin in human liver microsomes” Clin Cancer Res 11:1608-17 (Feb. 15, 2005).
[cited by applicant]
Quintieri et al., “In vitro cytotoxicity, cell cycle effects and DNA-binding properties of PNU-159682” Abstract (Abs #4649) Proceedings of the American Association of Cancer Research, pp. 925 (2003).
[cited by applicant]
Ravetch et al., “Fc receptors” Annu Rev Immunol. 9:457-92 (1991).
[cited by applicant]
Riechmann et al., “Reshaping Human Antibodies for Therapy” Nature 332(24):323-327 (Mar. 24, 1988).
[cited by applicant]
Ripamonti et al., “In vivo anti-tumour activity of FCE 23762, a methoxymorpholinyl derivative of doxorubicin active on doxorubicin-resistant tumour cells” Br J Cancer 65(5):703-707 ( 1992).
[cited by applicant]
Ripka et al., “Two chinese hamster ovary glycosylation mutants affected in the conversion of GDP-mannose to GDP-fucose” Arch Biochem Biophys 249(2):533-545 (Sep. 1986).
[cited by applicant]
Rodrigues et al., “Synthesis and Beta-Lactamase-mediated activation of a cephalosporin-taxol prodrug” Chemistry and Biology 2(4):223-227 (Apr. 1995).
[cited by applicant]
Rosok et al., “A combinatorial library strategy for the rapid humanization of anticarcinoma BR96 Fab” J Biol Chem 271(37):22611-22618 (Sep. 13, 1996).
[cited by applicant]
Saleh et al., “Phase I trial of the anti-Lewis Y drug immunoconjugate BR96-doxorubicin in patients with lewis Y-expressing epithelial tumors” J Clin Oncol 18(11):2282-2292 ( 2000).
[cited by applicant]
Sheehan et al., “Phage and Yeast Display,” Microbiol Spectrum 3(1): AID-0028-2014; 17 pages (2015).
[cited by applicant]
Shields et al. et al., “High resolution mapping of the binding site on human IgG1 for Fc gamma RI, Fc gamma RII, Fc gamma RIII, and FcRn and design of IgG1 variants with improved binding to the Fc gamma R” J Biol Chem 2…
[cited by applicant]
Sica et al., “B7-H4, a molecule of the B7 family, negatively regulates T cell immunity” Immunity 18(6):849-861 (Jun. 2003).
[cited by applicant]
Sidhu et al., “Phage-displayed antibody libraries of synthetic heavy chain complementarity determining regions” J Mol Biol 338(2):299-310 ( 2004).
[cited by applicant]
Sims et al., “A Humanized CD18 Antibody Can Block Function Without Cell Destruction” J Immunol 151(4):2296-2308 (Aug. 15, 1993).
[cited by applicant]
Storm et al., “Effect of small changes in orientation on reaction rate” J Am Chem Soc 94:5815-5825 ( 1972).
[cited by applicant]
Suh et al., “Generation and Characterization of B7-H4/B7S1/B7x-Deficient Mice” Mol. Cell. Biol. 26(17):6403-6411 (Sep. 2006).
[cited by applicant]
Sun et al., “Enabling ScFvs as multi-drug carriers: a dendritic approach” Bioorg Med Chem 11:1761-1768 ( 2003).
[cited by applicant]
Sun et al., “Syntheses of Dendritic Linkers Containing Chlorambucil REsidues for the Preparation of Antibody-Multidrug Immunoconjugates” Bioorg Med Chem Lett 12(16):2213-2215 (Apr. 19, 2002).
[cited by applicant]
Teicher, “Antibody-Drug Conjugate Targets” Current Cancer Drug Targets 9:982-1004 ( 2009).
[cited by applicant]
Thurston et al., “Synthesis of DNA-Interactive Pyrrolo[2,1-c] [1,4]benzodiazepines” Chem Rev 94:433-465 ( 1994).
[cited by applicant]
Toki et al., “Protease-Mediated Fragmentation of p-Amidobenzyl Ethers: A New Strategy for the Activation of Anticancer Prodrugs” J. Org. Chem. 67(6):1866-1872 ( 2002).
[cited by applicant]
Tolcher et al., “Randomized phase II study of BR96-doxorubicin conjugate in patients with metastatic breast cancer” J Clin Oncol 17(2):478-484 ( 1999).
[cited by applicant]
Torgov et al., “Generation of an intensely potent anthracycline by a monoclonal antibody-(beta)-galactosidase conjugate” Bioconjugate Chemistry 16:717-721 ( 2005).
[cited by applicant]
Traunecker et al., “Bispecific Single Chain Molecules (Janusins) Target Cytotoxic Lymphocytes on HIV Infected Cells” EMBO J 10(12):3655-3659 ( 1991).
[cited by applicant]
Tutt et al., “Trispecific F(ab')3 Derivatives that Use Cooperative Signaling Via the TCR/CD3 Complex and CD2 To Activate and Redirect Resting Cytotoxic T Cells” J Immunol 147(1):60-69 (Jul. 1991).
[cited by applicant]
Urlaub et al., “Isolation of chinese hamster cell mutants deficient in dihydrofolate reductase activity” P Natl Acad Sci USA 77(7):4216 (Jul. 1980).
[cited by applicant]
Van Dijk and van de Winkel, “Human antibodies as next generation therapeutics” Curr Opin Chem Biol 5(4):368-74 (Aug. 2001).
[cited by applicant]
Van Dongen et al., “Immuno-PET: A navigator in monoclonal antibody development and applications” Oncologist 12:1379-1389 ( 2007).
[cited by applicant]
Van Regenmortel “Development of a Preventive HIV Vaccine Requires Solving Inverse Problems Which is Unattainable by Rational Vaccine Design,” Front Immunol. 8: 2009 (2018).
[cited by applicant]
Verel et al., “
[cited by applicant]
Vollmers and Brandlein, “The ‘early birds’: Natural IgM antibodies and immune surveillance” Histol Histopathol 20:927-937 ( 2005).
[cited by applicant]
Walker, “A High Yielding Synthesis of N-Alkyl Maleimides Using a Novel Modification of the Mitsunobu Reaction” J. Org. Chem. 60(16):5352-5355 ( 1995).
[cited by applicant]
Widdison et al., “Semisynthetic Maytansine Analogues for the Targeted Treatment of Cancer” J Med Chem 49:4392-4408 ( 2006).
[cited by applicant]
Winter et al., “Making antibodies by phage display technology” Annu Rev Immunol 12:433-455 ( 1994).
[cited by applicant]
Woyke et al., “In vitro activities and postantifungal effects of the potent dolastatin 10 derivative auristatin PHE” Antimicrob Agents Chemother 45(12):3580-3584 (Dec. 2001).
[cited by applicant]
Wright et al., “Effect of glycosylation on antibody function: implications for genetic engineering” Trends Biotechnol. 15(1):26-32 ( 1997).
[cited by applicant]
Xu et al., “Expression and clinical significance of CD133 and B7-H4 in non-small cell lung cancer” Jiangsu Med. J. 37(4): 412-415 (2011) (English Abstract).
[cited by applicant]
Yamane-Ohnuki et al., “Establishment of FUT8 knockout Chinese hamster ovary cells: an ideal host cell line for producing completely defucosylated antibodies with enhanced antibody-dependent cellular cytotoxicity” Biotec…
[cited by applicant]
Yu et al., “The biosynthetic gene cluster of the maytansinoid antitumor agent ansamitocin from Actinosynnema pretiosum” PNAS 66(12):7968-7973 (Jun. 11, 2002).
[cited by applicant]
Zhou et al., “Structural Repertoire of HIV-1-Neutralizing Antibodies Targeting the CD4 Supersite in 14 Donors,” Cell 161: 1280-1292 (2015).
[cited by applicant]
Zhu et al., “B7-H4-deficient mice display augmented neutrophil-mediated innate immunity” Blood 113(8):1759-1767 ( 2009).
[cited by applicant]