Granted Patent
B2
US 12,234,270 · App. 17/718,087 · Granted Feb 25, 2025
IL-12 heterodimeric Fc-fusion proteins
Inventors:
Matthew Bernett (Monrovia, CA); John R. Desjarlais (Pasadena, CA); Rajat Varma (Hamden, CT); Ke Liu (Glendora, CA); Nargess Hassanzadeh-Kiabi (Pasadena, CA); Rumana Rashid (Temple City, CA)
Assignee:
Xencor, Inc.
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Abstract
The present invention provides novel IL-12 Fc fusion proteins, methods of making and using the same. The IL-12 Fc fusion proteins are useful for treatment of cancer and can be used in combination with checkpoint blockade.
Claims (2)
1. A composition comprising a variant IL-12p40 subunit domain, wherein said variant IL-12p40 subunit domain comprises amino acid substitutions selected from the group consisting of E59K, E59K/K99Y, and E59K/K99Y/C252S, wherein said variant IL-12p40 subunit domain has at least 90% sequence identity to SEQ ID NO: 4.
2. A composition comprising a variant IL-12p40 subunit domain, wherein said variant IL-12p40 subunit domain comprises E59K/K99Y/C252S amino acid substitutions, and wherein said variant IL-12p40 subunit domain has at least 90% sequence identity to SEQ ID NO: 4.
Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Mar 22, 2023
From: BERNETT, MATTHEW; DESJARLAIS, JOHN R.; VARMA, RAJAT; LIU, KE; HASSANZADEH-KIABI, NARGESS; RASHID, RUMANA
To: XENCOR, INC.
Reel/Frame 063064/0839 →
Continuity (5)
Provisional Application
62848512
· May 15, 2019
Provisional Application
62810038
· Feb 25, 2019
Provisional Application
62740813
· Oct 3, 2018
References Cited (56)
US 5650492A
· Gately et al.
· 1997
[cited by applicant]
US 5744132A
· Warne et al.
· 1998
[cited by applicant]
US 6617135B1
· Gillies et al.
· 2003
[cited by applicant]
US 7141651B2
· Gillies et al.
· 2006
[cited by applicant]
EP 1418184
· 2004
[cited by applicant]
KR 100827757B1
· 2008
[cited by applicant]
WO WO1999029732A2
· 1999
[cited by applicant]
WO WO2001007081A1
· 2001
[cited by applicant]
WO WO2001010912
· 2001
[cited by applicant]
WO WO2001010912A1
· 2001
[cited by applicant]
WO WO2001058957A2
· 2001
[cited by applicant]
WO WO2001068802A2
· 2001
[cited by applicant]
WO WO2002002143A2
· 2002
[cited by applicant]
WO WO2002066514A2
· 2002
[cited by applicant]
WO WO2002072605A2
· 2002
[cited by applicant]
WO WO2002066514A3
· 2003
[cited by applicant]
WO WO2007076933A1
· 2007
[cited by applicant]
WO WO2007084364A2
· 2007
[cited by applicant]
WO WO2008134879A1
· 2008
[cited by applicant]
WO WO2011082301A2
· 2011
[cited by applicant]
WO WO2013053775A1
· 2013
[cited by applicant]
WO WO2013090296A1
· 2013
[cited by applicant]
WO WO2015095249A1
· 2015
[cited by applicant]
WO WO2016048903A1
· 2016
[cited by applicant]
WO WO2017041739A1
· 2017
[cited by applicant]
WO WO2017062953A1
· 2017
[cited by applicant]
WO WO2018030806A1
· 2018
[cited by applicant]
WO WO2018068008A1
· 2018
[cited by applicant]
WO WO2018213731A1
· 2018
[cited by applicant]
WO WO2019006472
· 2019
[cited by applicant]
WO WO2019129053
· 2019
[cited by applicant]
WO WO2020072821
· 2020
[cited by applicant]
WO WO2020086758
· 2020
[cited by applicant]
Edelman et al., The covalent structure of an entire γG immunoglobulin molecule., Proc Natl Acad Sci U S A. May 1969; 63(1): 78-85.
[cited by applicant]
Holscher C., “The power of combinatorial immunology: IL-12 and IL-12-related dimeric cytokines in infectious diseases”, Medical Microbiology and Immunology, Springer, Berlin, DE, vol. 193, No. 1, Jun. 27, 2003 (Jun. 27,…
[cited by applicant]
Ha et al., “Immunoglobulin Fe Heterodimer Platform Technology: From Design to Applications in Therapeutic Antibodies and Proteins”, Frontiers in Immunology, vol. 7, Oct. 6, 2016 (Oct. 6, 2016), pp. 1-16, XP055377975, DO…
[cited by applicant]
Jung et al., Heterodimeric Fc-fused IL12 shows potent antitumor activity by generating memory CD8
[cited by applicant]
Fallon et al., Enhanced antitumor effects by combining an IL-12/anti-DNA fusion protein with avelumab, an anti-PD-L1 antibody., Oncotarget, 2017, vol. 8, (No. 13), pp. 20558-20571.
[cited by applicant]
Strauss et al., First-in-Human Phase I Trial of a Tumor-Targeted Cytokine (NHS-IL12) in Subjects with Metastatic Solid Tumors., Clinical Trials: Immunotherapy, Clin Cancer Res; 25(1) Jan. 1, 2019.
[cited by applicant]
Kiefer et al., Immunocytokines and bispecific antibodies: two complementary strategies for the selective activation of immune cells at the tumor site., Immunol Rev Mar. 2016;270(1):178-92. doi: 10.1111/imr.12391.
[cited by applicant]
Wells, Additivity of mutational effects in proteins., Biochemistry 1990, 29, 37, 8509-8517.
[cited by applicant]
Ngo et al. “The Protein Folding Problem and Tertiary Structure Prediction, Chapter 14: Computational Complexity Protein Structure Prediction, and the Levinthal Paradox” pp. 433-440 and 492-495 only, (1994).
[cited by applicant]
Bork, Powers and Pitfalls in Sequence Analysis: The 70% Hurdle., (2000) Genome Research 10:398.
[cited by applicant]
Skolnick et al., From genes to protein structure and function: novel applications of computational approaches in the genomic era., (2000) Trends in Biotech. 18(1): 34.
[cited by applicant]
Doerks et al., Protein annotation: detective work for function prediction., (1998) Trends in Genetics 14(6): 248.
[cited by applicant]
Brenner, Errors in genome annotation., (1999) Trends in Genetics 15(4): 132.
[cited by applicant]
Keunok et al., “Heterodimeric Fc-fused IL12 shows potent antitumor activity by generating memory CD8 + T cells”, Oncoinimmunology, vol. {0} 7, No. {0} 7, Mar. 6, 2018 (Mar. 6, 2018), page e1438800, XP055653232.
[cited by applicant]