IP Library › Granted Patent US 12,570,708
Granted Patent B2
US 12,570,708 · App. 18/761,743 · Granted Mar 10, 2026

Recombinant proteins and their therapeutic uses

Inventors: Keith Alan Charlton (Aberdeen, GB); Erik D'Hondt (Bazel, BE)
C07K14/485A61K39/0005A61K39/0011C07K14/28C07K14/4748C07K14/475C07K14/4753C07K14/48C07K14/495C07K14/50C07K14/65C07K14/71C12N9/12C12N9/6424A61K2039/645A61K2039/70C07K2319/40Y02P20/582
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Quick Facts
Patent No.
US 12,570,708
App. No.
18/761,743
Granted
Mar 10, 2026
Kind
B2
Abstract

A recombinant protein expressing one or more human growth factors, tumor antigens, and/or receptors or epitopes thereof on or within an immunogenic expression creating a recombinant protein in which one or more epitopes are presented on the surface of the sequence in their natural configuration. The growth factor, tumor antigen, and/or receptor, sequence(s) may be expressed within the encoding sequence at appropriate internal positions or at the termini as single expressions or as two or more tandem repeats.

Claims (13)

1 . A recombinant protein, comprising:

an immunogenic polypeptide; and

a polypeptide comprising Cys6, Cys14, Cys20, Cys31, and Cys33 of human Epidermal Growth Factor (SEQ ID NO: 25), wherein the polypeptide includes a single mutation of Cys33 selected from the group consisting of Ala33 or Gly33.

2 . The recombinant protein according to claim 1 , wherein said immunogenic polypeptide sequence includes a cholera toxin B (CT-B) protein.

3 . The recombinant protein according to claim 1 , wherein the polypeptide includes a full length or neutralizing domain of at least two different growth factors.

4 . The recombinant protein according claim 1 , wherein the polypeptide includes a full length or neutralizing domain of one or more growth factors in said protein as a single domain or as two or more tandem repeats.

5 . The recombinant protein according claim 1 , wherein the immunogenic polypeptide and the polypeptide are separated by a peptide spacer.

6 . A recombinant protein according claim 5 , wherein said peptide spacer comprises in part a growth factor or neutralizing domain thereof.

7 . A recombinant protein according claim 5 , wherein said peptide spacer includes one or more host T-cell epitopes or said peptide spacer is selected from the group consisting of SSGGG (SEQ. ID NO: 4), GGSGG (SEQ. ID NO: 3), SSGGGSGG (SEQ. ID NO: 8), SSGGGGSGGG (SEQ. ID NO: 9), TSGGGSG (SEQ. ID NO: 10), TSGGGGSGG (SEQ. ID NO: 11), SSGGGSGGSSG (SEQ. ID NO: 12), GGSGGTSGGGSG (SEQ. ID NO: 13), SGGTSGGGGSGG (SEQ. ID NO: 14), GGSGGTSGGGGSGG (SEQ. ID NO: 15), SSGGGGSGGGSSG (SEQ. ID NO: 16), SSGGGSGGSSGGG (SEQ. ID NO: 17), SSGGGGSGGGSSGGG (SEQ. ID NO: 18), and GGSGGTRPSTAATS (SEQ. ID NO: 19).

8 . A process of preparing a multivalent molecule comprising:

assembling multimers from monomeric sub-units of the recombinant protein of claim 1 to form a multivalent molecule.

9 . A process of preparing a vaccine formulation comprising:

mixing one or more multivalent molecules of claim 8 together to prepare the vaccine formulation.

Continuity (7)
Continuation 17521121 · Nov 8, 2021
Continuation 15814723 · Nov 16, 2017
Continuation 14996553 · Jan 15, 2016
Continuation 13813844
Provisional Application 61654401 · Jun 1, 2012
Provisional Application 61563128 · Nov 23, 2011
Related Publication 20250066439A1 · Feb 27, 2025
References Cited (51)
US 5894018A · Davila et al. · 1999 [cited by applicant]
US 5984018A · Yamamoto et al. · 1999 [cited by applicant]
US 7201905B2 · Chen et al. · 2007 [cited by applicant]
US 7320795B2 · Milich et al. · 2008 [cited by applicant]
US 7763243B2 · Lum et al. · 2010 [cited by applicant]
US 9902760B2 · Charlton et al. · 2018 [cited by applicant]
US 11198716B2 · Charlton et al. · 2021 [cited by applicant]
US 20020094956A1 · Cosgrove · 2002 [cited by applicant]
US 20030176655A1 · Shi et al. · 2003 [cited by applicant]
US 20050037967A1 · Rosenblum · 2005 [cited by applicant]
US 20050130886A1 · Holmgren et al. · 2005 [cited by applicant]
US 20060194292A1 · Upton et al. · 2006 [cited by applicant]
US 20060246087A1 · Arakawa et al. · 2006 [cited by applicant]
US 20080170991A1 · Shi et al. · 2008 [cited by applicant]
US 20080176934A1 · Verbeuren et al. · 2008 [cited by applicant]
US 20100226923A1 · Rao et al. · 2010 [cited by applicant]
US 20120065380A1 · Yoo et al. · 2012 [cited by applicant]
CN 101595219A · 2009 [cited by applicant]
EP 1921149A1 · 2008 [cited by applicant]
EP 2041177 · 2011 [cited by applicant]
JP H07285883 · 1995 [cited by applicant]
JP 2005052135A · 2005 [cited by applicant]
JP 2009543071A · 2009 [cited by applicant]
JP 2010508861A · 2010 [cited by applicant]
JP 2011187653A · 2011 [cited by applicant]
WO 2007118660A2 · 2007 [cited by applicant]
WO 2008005992A2 · 2008 [cited by applicant]
WO 2008058944A1 · 2008 [cited by applicant]
WO 2012058768A1 · 2012 [cited by applicant]
Kazemi et al (Biotechnology and Environmental Science: Molecular Approaches, pp. 211-218, 1992). [cited by applicant]
Li. S et al., Pentabody-mediated antigen delivery induces antigen-specific mucosal immune response:, Molecular immunology, Pergamon, GB, vol. 46, No. 8-9, May 1, 2009, pp. 1718-1726. [cited by applicant]
Jiang Hua et al., “Application of EGFP-EGF fusions to explore mechanism of endocytosis of epidermal growth factor”, Acta Pharmacologica Sinica, vol. 28., No. 1, Jan. 2007, pp. 111-117. [cited by applicant]
Lebens M. et al., a mucosally administered recombinant fusion protein vaccine against schistosomiasis protecting against immunopathology and infection:, Vaccine, Elsevier Ltd., GB, vol. 21., No. 5-6, Jan. 17, 2003. [cited by applicant]
Bargou M.D., Ralf C. et al. Sustained Response During Seen after Treatment with Single Agent Blinatumomab MT103/MEDI-538) in the Ongoing Phase I Study MT103-104 in Patients with Relapsed NHL. 50th ASH annual Meeting and… [cited by applicant]
Dixit, Rakesh, et al. Toxicokinetics and Physiologically Based Toxicokinetics in Toxicology and Risk Assessment. Journal of Toxicology and Environmental Health Part B: Critical Reviews, 6(1): 1-40, 2011. [cited by applicant]
Lum M.D., Lawrence G. T Cell-Based Immunotherapy For Cancer: A Virtual Reality? CA-A Cancer Journal for Clinicians, 49(2): 74-100, 1999. [cited by applicant]
Geuijan Cecilia A.W., et al. A Proteomic Approach to Tumour Target Identification Using PH Display, Affinity Purification and Mass Spectrometry. European Journal of Cancer, 41(1): 178-187, 2005. [cited by applicant]
Dong, Jianying et al. A Stable IgG-like Bispecific Antibody Targeting the Epidermal Growth Factor Receptor and the Type 1 Insulin-like Growth Factor Receptor Demonstrates Superior Anti-Tumor Activity. Landes Bioscience … [cited by applicant]
Moore, Paul A. et al. Applicaton of Dual Affinity Retargeting Molecules to Achieve Optimal Redirected Cell Killing of B-cell Lymphoma. Blood Journal. The American Society of Hematology, 117(17): 4542-4551, 2011. [cited by applicant]
Schoeberl, Birgit. Mathematical Modeling of Signal Transduction Pathways In Mammalian Cells at the Example Jf the EGF Induced MAP Kinase Cascade and TNF Receptor Crosstalk. Stuttgart, Univ. Diss., 2004. [cited by applicant]
Mabry, Robert, et al. Engineering of Stable Bispecific Antibodies Targeting IL-17A and IL-23. Protein Engineering, Design & Selection, 23(3): 115-127, 2010. [cited by applicant]
Strop, Pavel et al. Generating Bispecific Human IgG1 and IgG2 Anitbodies from Any Anitbody Pair. Journal of Molecular Biology, 420(3): 204-219, 2012. [cited by applicant]
K.N. Srinivasan, P. et al., Scorpion, a Molecular Database of Scorpion Toxins. Toxicon, 40(1 ): 23-31, 2002. [cited by applicant]
Chu, PhD, Seung Y. et al., Reduction of Total IgE by Targeted Coengagement of IgE B-Cell Receptor and FcyRllb with Fe-Engineered Antibody. Journal of Allergy and Clinical Immunology, 129(4): 1102-1115, 2012. [cited by applicant]
Zhukovsky E., et al. Recruit-Tandab AFM13—Overcoming Limitations of Monoclonal Antibodies in Hodkin Lymphoma. European Society for Medical Oncology, 23(9): ix350-ix351, 2012. [cited by applicant]
Wang et al. Cancer Biotherapy & Radiopharmaceuticals vol. 17, No. 6, pp. 665-671, 2002. [cited by applicant]
Zimmermann et al. Hybridoma vol. 10, No. 1, pp. 65-76, 1991. [cited by applicant]
Extended European Search Report in corresponding EP application No. 20170470.7 dated Oct. 26, 2020. [cited by applicant]
Lu, B. et al. Isomers of Epidermal Growth Factor with Ser Cys Mutation at the N-Terminal Sequence: Isomerization, Stability, Unfolding, Refolding, and Structure dated Jul. 18, 2005. [cited by applicant]
Zhang, Z. et al. Entropic Folding Pathway of Human Epidermal Growth Factor Explored by Disulfide Scrambling and Amplified Collective Motion Simulations dated Jul. 26, 2006. [cited by applicant]
Stortelers, C. et al. Epidermal Growth Factor Contains Both Positive and Negative Determinants for Interaction with ErbB-2/ErbB-3 Heterodimers dated Nov. 2, 2001. [cited by applicant]