IP Library › Granted Patent US 12,338,293
Granted Patent B2
US 12,338,293 · App. 17/702,329 · Granted Jun 24, 2025

UPAR antibodies and fusion proteins with the same

Inventors: Jijun Dong (Weston, MA); Pinar Gurel (Cambridge, MA); Joshua Heiber (Watertown, MA); Yuan Hu (Belmont, MA)
Assignee: Mural Oncology, Inc.
C07K16/2896A61P35/00C07K14/5434A61K38/00A61K2039/505A61K2039/54A61K2039/545C07K2317/24C07K2317/55C07K2317/565C07K2317/622C07K2317/92C07K2319/30
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 12,338,293
App. No.
17/702,329
Granted
Jun 24, 2025
Kind
B2
Abstract

The disclosure provides urokinase plasminogen activator receptor (uPAR) binding polypeptides (e.g., uPAR antigen binding proteins), and fusion proteins comprising said uPAR binding polypeptides and a cytokine or variant thereof. The disclosure further provides pharmaceutical compositions comprising the uPAR binding polypeptides and fusion proteins of the disclosure and methods of treating cancer with the same. The disclosure further provides engineered IL-12 p35 and p40 polypeptides.

Claims (22)

1. A kit comprising a first pharmaceutical composition comprising a first fusion protein and a second pharmaceutical composition comprising a second fusion protein, wherein:

(a) the first fusion protein comprises:

(i) an antigen binding domain that binds specifically to a first epitope on urokinase plasminogen activator receptor (uPAR) comprising a heavy chain variable domain comprising a CDR1, a CDR2, and a CDR3 of SEQ ID NOs: 41, 20, and 21, respectively, and a light chain variable domain comprising a light chain variable domain comprising a CDR1, a CDR2, and a CDR3 of SEQ ID NOs: 22-24, respectively; and

(ii) a IL-12 p35 subunit comprising SEQ ID NO: 81, optionally wherein the IL-12 p35 subunit comprises one or more of the following amino acid substitutions in SEQ ID NO: 81 selected from the group of: M12S, S27D, N28R, Q35E, F39D, F39H, S44K, C74K, C74D, C74W, C74Y, C74Q, M111F, M111W, V114I, M119L, M145L, F150Y, L161D, L161Q, and D188N; and

(b) the second fusion protein comprises:

(i) an antigen binding domain that binds specifically to a second epitope on uPAR comprising a heavy chain variable domain comprising a CDR1, a CDR2, and a CDR3 of SEQ ID NOs: 3-5, respectively, and a light chain variable domain comprising a light chain variable domain comprising a CDR1, a CDR2, and a CDR3 of SEQ ID NOs: 6-8, respectively; and

(ii) a IL-12 p40 subunit comprising SEQ ID NO: 84, optionally wherein the IL-12 p40 subunit comprises one or two of the following amino acid substitutions in SEQ ID NO: 84: C177S, C177F, C177M, C177H, C177I, C177Q, and C252S.

2. The kit of claim 1 , wherein the antigen binding domain that binds specifically to the first epitope on uPAR comprises a heavy chain variable domain comprising SEQ ID NO: 37 and a light chain variable domain comprising SEQ ID NO: 40.

3. The kit of claim 1 , wherein the antigen binding domain that binds specifically to the second epitope on uPAR comprises a heavy chain variable domain comprising SEQ ID NO: 34 and a light chain variable domain comprising SEQ ID NO: 35.

4. The kit of claim 3 , wherein the light chain variable domain of the antigen binding domain that binds specifically to the second epitope on uPAR further comprises a light chain constant domain.

5. The kit of claim 4 , wherein the light chain constant domain comprises a lambda light chain constant domain.

6. The kit of claim 1 , wherein the IL-12 p35 subunit comprises the following amino acid substitutions in SEQ ID NO: 81: S27D, C74K, and D188N.

7. The kit of claim 6 , wherein the IL-12 p35 subunit comprises a sequence of SEQ ID NO: 83.

8. The kit of claim 1 , wherein the IL-12 p40 subunit comprises the following amino acid substitutions in SEQ ID NO: 84: C177S and C252S.

9. The kit of claim 8 , wherein the IL-12 p40 subunit comprises a sequence of SEQ ID NO: 87.

10. The kit of claim 1 , wherein the first fusion protein further comprises a linker disposed between the antigen binding domain that specifically binds to a first epitope on uPAR and the IL-12 p35 subunit, optionally, wherein the linker comprises (GGGGS) n (SEQ ID NO: 148), wherein N=2.

11. The kit of claim 10 , wherein the first fusion protein further comprises a second antigen binding domain that specifically binds to the first epitope on uPAR.

12. The kit of claim 11 , wherein the first fusion protein comprises a sequence of SEQ ID NO: 213.

13. The kit of claim 1 , wherein the second fusion protein comprises a first polypeptide and a second polypeptide, wherein the first polypeptide comprises the heavy chain variable domain of the antigen binding domain that specifically binds to the second epitope on uPAR fused to the IL-12 p40 subunit, wherein a linker is disposed between the heavy chain variable domain of the antigen binding domain that specifically binds to the second epitope on uPAR and the IL-12 p40 subunit; and

the second polypeptide comprises the light chain variable domain of the antigen binding domain that specifically binds to the second epitope on uPAR fused to a lambda light chain constant domain.

14. The kit of claim 13 , wherein the first polypeptide comprises a sequence of SEQ ID NO: 179 and the second polypeptide comprises a sequence of SEQ ID NO: 159.

15. The kit of claim 13 , wherein the linker comprises (GGGGS)n (SEQ ID NO: 148), wherein N=2.

Assignments (7)
RELEASE OF PATENT SECURITY AGREEMENTS Recorded Dec 24, 2024
From: MORGAN STANLEY SENIOR FUNDING, INC.
To: ALKERMES, INC.
Reel/Frame 069771/0616 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 16, 2024
From: ALKERMES, INC.
To: ALKERMES PLC
Reel/Frame 066479/0714 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 16, 2024
From: ALKERMES PLC
To: MURAL ONCOLOGY, INC.
Reel/Frame 066479/0814 →
RELEASE OF SECURITY INTEREST Recorded Nov 21, 2023
From: MORGAN STANLEY SENIOR FUNDING, INC.
To: ALKERMES PHARMA IRELAND LIMITED
Reel/Frame 065637/0300 →
SECURITY AGREEMENT Recorded Jul 17, 2023
From: ALKERMES, INC.
To: MORGAN STANLEY SENIOR FUNDING, INC.
Reel/Frame 064286/0931 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 28, 2022
From: DONG, JIJUN; GUREL, PINAR; HEIBER, JOSHUA
To: ALKERMES, INC.
Reel/Frame 061243/0280 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 28, 2022
From: HU, YUAN
To: ALKERMES, INC.
Reel/Frame 061243/0388 →
Continuity (2)
Provisional Application 63165313 · Mar 24, 2021
Related Publication 20220340678A1 · Oct 27, 2022
References Cited (167)
US 3992518A · Chien et al. · 1976 [cited by applicant]
US 5635599A · Pastan et al. · 1997 [cited by applicant]
US 5660848A · Moo-Young · 1997 [cited by applicant]
US 5756115A · Moo-Young et al. · 1998 [cited by applicant]
US 5821333A · Carter et al. · 1998 [cited by applicant]
US 5874104A · Adler-Moore et al. · 1999 [cited by applicant]
US 5916588A · Popsecu · 1999 [cited by applicant]
US 6011002A · Pastan et al. · 2000 [cited by applicant]
US 6043094A · Martin et al. · 2000 [cited by applicant]
US 6056973A · Allen et al. · 2000 [cited by applicant]
US 6126966A · Abra et al. · 2000 [cited by applicant]
US 6193980B1 · Efstathiou et al. · 2001 [cited by applicant]
US 6316024B1 · Allen et al. · 2001 [cited by applicant]
US 6715485B1 · Djupesland · 2004 [cited by applicant]
US 8734774B2 · Frelinger et al. · 2014 [cited by applicant]
US 9156897B2 · Alvarez et al. · 2015 [cited by applicant]
US 9212230B2 · Schuurman et al. · 2015 [cited by applicant]
US 9296801B2 · Alvarez et al. · 2016 [cited by applicant]
US 9359415B2 · Alvarez et al. · 2016 [cited by applicant]
US 9428563B2 · Alvarez · 2016 [cited by applicant]
US 9499634B2 · Dixit et al. · 2016 [cited by applicant]
US 10023623B2 · Alvarez et al. · 2018 [cited by applicant]
US 10183979B2 · Alvarez et al. · 2019 [cited by applicant]
US 10407481B2 · Alvarez · 2019 [cited by applicant]
US 11945870B2 · Losey et al. · 2024 [cited by applicant]
US 20040002585A1 · Holgersson · 2004 [cited by applicant]
US 20050260222A1 · Gupta et al. · 2005 [cited by applicant]
US 20050265995A1 · Tomlinson et al. · 2005 [cited by applicant]
US 20050287144A1 · Wallach et al. · 2005 [cited by applicant]
US 20070264234A1 · Sayers et al. · 2007 [cited by applicant]
US 20080152587A1 · Zhou et al. · 2008 [cited by applicant]
US 20080286211A1 · Barker · 2008 [cited by applicant]
US 20080300193A1 · Ahn et al. · 2008 [cited by applicant]
US 20100150945A1 · Bigler · 2010 [cited by examiner]
US 20100239554A1 · Schellenberger · 2010 [cited by applicant]
US 20100261872A1 · DeFrees et al. · 2010 [cited by applicant]
US 20100298236A1 · Grotzinger et al. · 2010 [cited by applicant]
US 20110112179A1 · Airan et al. · 2011 [cited by applicant]
US 20110243932A1 · Barrett et al. · 2011 [cited by applicant]
US 20120028911A1 · Shebuski et al. · 2012 [cited by applicant]
US 20130040845A1 · Springer et al. · 2013 [cited by applicant]
US 20130336924A1 · Alvarez et al. · 2013 [cited by applicant]
US 20130336925A1 · Alvarez et al. · 2013 [cited by applicant]
US 20130338067A1 · Alvarez et al. · 2013 [cited by applicant]
US 20140154254A1 · Kannan et al. · 2014 [cited by applicant]
US 20140234962A1 · Alvarez · 2014 [cited by applicant]
US 20150307628A1 · Kim et al. · 2015 [cited by applicant]
US 20160052983A1 · Alvarez et al. · 2016 [cited by applicant]
US 20160237132A1 · Alvarez et al. · 2016 [cited by applicant]
US 20170044228A1 · Alvarez · 2017 [cited by applicant]
US 20170233447A1 · Qin · 2017 [cited by applicant]
US 20180179273A1 · Fog et al. · 2018 [cited by applicant]
US 20180264110A1 · Yoo · 2018 [cited by examiner]
US 20200024337A1 · Kallunki · 2020 [cited by examiner]
US 20200040053A1 · Alvarez · 2020 [cited by applicant]
US 20200317758A1 · Torres · 2020 [cited by examiner]
JP 2003513656 · 2003 [cited by applicant]
JP 2003514552 · 2003 [cited by applicant]
JP 2004528014 · 2004 [cited by applicant]
JP 2005514442 · 2005 [cited by applicant]
JP 2006517191 · 2006 [cited by applicant]
JP 2008504001 · 2008 [cited by applicant]
JP 2008521489 · 2008 [cited by applicant]
JP 2009512433 · 2009 [cited by applicant]
JP 2010536341 · 2010 [cited by applicant]
JP 6388408 · 2018 [cited by applicant]
WO WO1995027732 · 1995 [cited by applicant]
WO WO1999046392 · 1999 [cited by applicant]
WO WO2001096565 · 2001 [cited by applicant]
WO WO2002062375 · 2002 [cited by applicant]
WO WO2003059376 · 2003 [cited by applicant]
WO WO2004016740 · 2004 [cited by applicant]
WO WO2005016950 · 2005 [cited by applicant]
WO WO2005034863 · 2005 [cited by applicant]
WO WO2005116077A2 · 2005 [cited by applicant]
WO WO2007020889 · 2007 [cited by applicant]
WO WO2007046006 · 2007 [cited by applicant]
WO WO2007062844 · 2007 [cited by applicant]
WO WO2007063907 · 2007 [cited by applicant]
WO WO2007120693A2 · 2007 [cited by applicant]
WO WO2008072075 · 2008 [cited by applicant]
WO WO2008144757 · 2008 [cited by applicant]
WO WO2009002562 · 2008 [cited by applicant]
WO WO2009153960 · 2009 [cited by applicant]
WO WO2010020766 · 2010 [cited by applicant]
WO WO2010091122 · 2010 [cited by applicant]
WO WO2010127029 · 2010 [cited by applicant]
WO WO2011100620A2 · 2011 [cited by applicant]
WO WO2011103049 · 2011 [cited by applicant]
WO WO2011123683 · 2011 [cited by applicant]
WO WO2012016203 · 2012 [cited by applicant]
WO WO2012040323 · 2012 [cited by applicant]
WO WO2012062904 · 2012 [cited by applicant]
WO WO2013184938 · 2013 [cited by applicant]
WO WO2013184939 · 2013 [cited by applicant]
WO WO2015124297A1 · 2015 [cited by applicant]
WO WO2017062953A1 · 2017 [cited by examiner]
WO WO2019010219A1 · 2019 [cited by applicant]
WO WO2019209965A2 · 2019 [cited by applicant]
WO WO2020072821A2 · 2020 [cited by applicant]
Bhattacharya et al., Impact of genetic variation on three dimensional structure and function of proteins, 2017, PLOS One, vol. 12, Issue 3, pp. 1-22 (Year: 2017). [cited by examiner]
Fenton et al., Rheostat positions: A new classification of protein positions relevant to pharmacogenomics, 2020, Medicinal Chemistry Research, vol. 29, pp. 1133-1146 (Year: 2020). [cited by examiner]
Guo et al., Protein tolerance to random amino acid change, 2004, PNAS, vol. 101, No. 25, pp. 9205-9921 (Year: 2004). [cited by examiner]
Sommavilla et al., Expression, engineering and characterization of the tumor-targeting heterodimeric immunocytokine F8-IL12, 2010, Protein Engineering, Design & Selection, vol. 23, No. 8, pp. 653-661 (Year: 2010). [cited by examiner]
Rabbani et al., Urokinase Receptor Antibody Can Reduce Tumor Volume and Detect the Presence of Occult Tumor Metastases in Vivo, 2002, Cancer Research, vol. 62, pp. 2390-2397 (Year: 2002). [cited by examiner]
Kontermann et al., Dual targeting strategies with bispecific antibodies, 2012, mAbs, vol. 4, Issue 2, pp. 182-197 (Year: 2012). [cited by examiner]
Chen et al., Fusion Protein Linkers: Property, Design and Functionality, 2013, Advanced Drug Delivery, vol. 65, Issue 10, pp. 1357-1369 (Year: 2013). [cited by examiner]
Ma et al., Antibody stability: A key to performance—Analysis, influences and improvement, 2020, Biochimie, vol. 177, pp. 213-225 (Year: 2020). [cited by examiner]
Sela-Culang et al., The structural basis of antibody-antigen recognition, 2013, Frontiers in Immunology, vol. 4, Article 302, pp. 1-13 (Year: 2013). [cited by examiner]
Kussie et al., A Single Engineered Amino Acid Substitution Changes Antibody Fine Specificity, 1994, Journal of Immunology, pp. 146-152 (Year: 1994). [cited by examiner]
U.S. Appl. No. 61/657,264, Alvarez et al., filed Jun. 8, 2012. [cited by applicant]
Al-Lazikani et al., “Standard conformations for the canonical structures of immunoglobulins.” Journal of molecular biology, Nov. 7, 1997, 273(4):927-48. [cited by applicant]
atcc.org [online] “U-937 CRL-1593.2,” retrieved from URL<https://www.atcc.org/products/crl-1593.2?matchtype=&network=g&device=c&adposition=&keyword=&gad_source=1&gclid=EAIaIQobChMIoP686uODhQMVUpxaBR28owYDEAAYASAAEgLgUvB… [cited by applicant]
Bird et al., “Single-chain antigen-binding proteins,” Science, Oct. 21, 1988, 242(4877):423-6. [cited by applicant]
Cao et al., “Tim-4 inhibition of T-cell activation and T helper type 17 differentiation requires both the immunoglobulin V and mucin domains and occurs via the mitogen-activated protein kinase pathway,” Immunology, Jun.… [cited by applicant]
Carter, “Bispecific human IgG by design.” Journal of Immunological methods, Feb. 1, 2001, 248(1-2):7-15. [cited by applicant]
CAS No. 6132-04-3, “Sodium citrate tribasic dihydrate,” Sigma-Aldrich, retrieved on Mar. 22, 2024, retrieved from URL <https://www.sigmaaldrich.com/US/en/substance/294106132043>, 5 pages. [cited by applicant]
Chaudhary et al., “A rapid method of cloning functional variable-region antibody genes in [cited by applicant]
Chen et al., “Fusion protein linkers: property, design and functionality,” Advanced drug delivery reviews, Oct. 15, 2013, 65(10):1357-69. [cited by applicant]
Cooper et al., “T-cell clones can be rendered specific for CD19: toward the selective augmentation of the graft-versus-B-lineage leukemia effect,” Blood, 101(4):1637-1644, 2003. [cited by applicant]
Edelman “The covalent structure of an entire γG immunoglobulin molecule,” Proceedings of the National Academy of Sciences, May 1969, 63(1):78-85. [cited by applicant]
Fontenot et al., “Human immunodeficiency virus (HIV) antigen: Structure and serology of multivalent human mucin MUC1-HIV V3 chimeric proteins,” Proceedings of the National Academy of Sciences, Jan. 1995, 92(1):315-319. [cited by applicant]
Grassot et al., “RTKdb: database of receptor tyrosine kinase,” Nucleic Acids Research, Jan. 2003, 31(1):353-358. [cited by applicant]
Gunasekaran et al., “Enhancing antibody Fc heterodimer formation through electrostatic steering effects: applications to bispecific molecules and monovalent IgG.” Journal of Biological Chemistry, Jun. 18, 2010, 285(25):… [cited by applicant]
Heeley et al., “Mutations flanking the polyglutamine repeat in the modulatory domain of rat glucocorticoid receptor lead to an increase in affinity for hormone,” Endocrine research, Jan. 2002, 28(3):217-29. [cited by applicant]
Honegger et al., “Yet another numbering scheme for immunoglobulin variable domains: an automatic modeling and analysis tool,” J. Mol. Biol. Jun. 8, 2001; 309(3):657-70. [cited by applicant]
International Preliminary Report on Patentability in International Appln. No. PCT/US2013/044556, mailed on Nov. 15, 2013, 7 pages. [cited by applicant]
International Search Report and Written Opinion in International Appln. No. PCT/US2013/044556, mailed on Nov. 15, 2013, 9 pages. [cited by applicant]
Jones, “Proteinase mutants of Saccharomyces cerevisiae,” Genetics, Jan. 1977, 85(1):23-33. [cited by applicant]
Karlin et al., “Methods for assessing the statistical significance of molecular sequence features by using general scoring schemes,” Proceedings of the National Academy of Sciences, Mar. 1990, 87(6):2264-2268. [cited by applicant]
Kim et al., “Hybrid restriction enzymes: zinc finger fusions to Fok I cleavage domain,” Proceedings of the National Academy of Sciences, Feb. 1996, 93(3):1156-60. [cited by applicant]
Kingsman et al., “Replication in Saccharomyces cerevisiae of plasmid pBR313 carrying DNA from the yeast trpl region.” Gene, Oct. 1979, 7(2):141-52. [cited by applicant]
Klein et al., “Progress in overcoming the chain association issue in bispecific heterodimeric IgG antibodies.” MAbs, Nov. 2012, 4(6):653-663. [cited by applicant]
Labrijn et al., Efficient generation of stable bispecific IgG1 by controlled Fab-arm exchange. Proceedings of the National Academy of Sciences, Mar. 26, 2013, 110(13):5145-50. [cited by applicant]
Lefranc et al., “IMGT unique numbering for immunoglobulin and T cell receptor variable domains and Ig superfamily V-like domains,” Dev Comp Immunol, 2003, Jan. 27(1):55-77. [cited by applicant]
Liljeblad et al., “Analysis of agalacto-IgG in rheumatoid arthritis using surface plasmon resonance,” Glycoconjugate journal, May 2000, 17:323-9. [cited by applicant]
Liu et al., “Design of polydactyl zinc-finger proteins for unique addressing within complex genomes,” Proceedings of the National Academy of Sciences, May 1997, 94(11):5525-30. [cited by applicant]
MacCallum et al., “Antibody-antigen interactions: contact analysis and binding site topography,” Journal of molecular biology, Oct. 11, 1996, 262(5):732-45. [cited by applicant]
Merrifield, “Solid Phase Peptide Synthesis. I. The Synthesis of a Tetrapeptide,” Journal of the American Chemical Society, Jul. 1963, 85(14):2149-2154. [cited by applicant]
Mortler et al., “Soluble interleukin-15 receptor α (IL-15Rα)-sushi as a selective and potent agonist of IL-15 action through IL-15Rβ/γ: hyperagonist IL-15. IL-15Rα fusion proteins,” Journal of Biological Chemistry, Jan.… [cited by applicant]
Muda et al., “Therapeutic assessment of SEED: a new engineered antibody platform designed to generate mono-and bispecific antibodies.” Protein Engineering, Design & Selection, May 2011, 24(5):447-54. [cited by applicant]
Nayeem et al., “A comparative study of available software for high-accuracy homology modeling: From sequence alignments to structural models,” Protein Science, Apr. 2006, 15(4):808-824. [cited by applicant]
Nomellini et al., “S-layer-mediated display of the immunoglobulin G-binding domain of streptococcal protein G on the surface of Caulobacter crescentus: development of an immunoactive reagent,” Applied and environmental … [cited by applicant]
Puskas et al., “Development of an attenuated interleukin-2 fusion protein that can be activated by tumour-expressed proteases,” Immunology, Jun. 2011, 133(2):206-220. [cited by applicant]
Ridgway et al., “‘Knobs-into-holes’ engineering of antibody CH3 domains for heavy chain heterodimerization.” Protein Engineering, Design and Selection, Jul. 1996, 9(7):617-21. [cited by applicant]
Scheraga, “Predicting three-dimensional structures of oligopeptides,” Reviews in computational chemistry, Jan. 1992, 1:73-142. [cited by applicant]
Shen, “Deletion of the linker connecting the catalytic and cellulose-binding domains of endoglucanase A (CenA) of Cellulomonas fimi alters its conformation and catalytic activity,” Journal of Biological Chemistry, Jun. … [cited by applicant]
Shikari et al., “Effect Of Topical IL-IRA on Signs And Symptoms Of Dry Eye Disease In Patients With Ocular Graft-versus-host Disease (GVHD),” Investigative Ophthalmology & Visual Science, Mar. 2012, 53(14):579 (Abstract… [cited by applicant]
Simon et al., “Identification of a Urokinase Receptor-Integrin Interaction Site,” J. Biol. Chem., Apr. 2000, 275:10228-34. [cited by applicant]
Stinchcomb et al., “Isolation and characterisation of a yeast chromosomal replicator,” Nature, Nov. 1979, 282(5734):39-43. [cited by applicant]
Tatusova et al., “BLAST 2 Sequences, a new tool for comparing protein and nucleotide sequences,” FEMS Microbiology Letters, Aug. 1999, 177(1):187-188. [cited by applicant]
Tschemper et al., “Sequence of yeast DNA fragmant containing a chromosomal replicator and the TRP1 gene,” 1980, Gene, 10:157-166. [cited by applicant]
UniProt Accession No. P18510.1, “IL1RA_Human,” dated May 8, 2019, 9 pages. [cited by applicant]
UniProt Accession No. Q8N307, “Mucin-20”, dated Nov. 20, 2014, 6 pages. [cited by applicant]
Van der Pluijm G et al., “Urokinase-receptor/integrin complexes are functionally involved in adhesion and progression of human breast cancer in vivo,” The American journal of pathology, Sep. 2001, 159(3):971-82. [cited by applicant]
Wranik et al., “LUZ-Y, a novel platform for the mammalian cell production of full-length IgG-bispecific antibodies,” Journal of Biological Chemistry, Dec. 21, 2012, 287(52):43331-9. [cited by applicant]
Gonias et al., “Urokinase receptor and resistance to targeted anticancer agents”, [cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2022/021522, mailed Aug. 18, 2022, 12 pages. [cited by applicant]
Leong et al., “Optimized expression and specific activity of IL-12 by directed molecular evolution”, [cited by applicant]
Lin et al., “Structure-based Engineering of Species Selectivity in the Interaction between Urokinase and Its Receptor”, [cited by applicant]
Mazar et al., “Development of Novel Therapeutics Targeting the Urokinase Plasminogen Activator Receptor (uPAR) and Their Translation Toward the Clinic”, [cited by applicant]
Venetz et al., “Targeted Reconstitution of Cytokine Activity upon Antigen Binding using Split Cytokine Antibody Fusion Proteins”, [cited by applicant]
Bouchaud et al., “The Exon-3-Encoded Domain of IL-15Rα Contributes to IL-15 High-Affinity Binding and Is Crucial for the IL-15 Antagonistic Effect of Soluble IL-15Rα,” Journal of Molecular Biology, Sep. 2008, 382(1):1-1… [cited by applicant]
Office Action in Eurasian Appln. No. 202392665, mailed on Sep. 25, 2024, 7 pages (with English translation). [cited by applicant]
Office Action in Japanese Appln. No. 2023-085990, mailed on Apr. 23, 2024, 6 pages (with English translation). [cited by applicant]
Rowley et al., “Expression of IL-15RA or an IL-15/IL-15RA fusion on CD81 T cells modifies adoptively transferred T-cell function in cis,” European Journal of Immunology, Feb. 2009, 39(2):491-506. [cited by applicant]
Extended European Search Report in European Appln. No. 22776558.3, mailed on Jan. 21, 2025, 12 pages. [cited by applicant]