IP Library Granted Patent US 12,291,552
Granted Patent B2
US 12,291,552 · App. 17/729,534 · Granted May 6, 2025

Chimeric protein in the treatment of amyloidosis

Inventors: Christophe De Romeuf (Lambersart, FR); Christophe Sirac (Limoges, FR); Jean-Claude Brouet (Paris, FR)
Assignees: CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (CNRS); UNIVERSITÉDE LIMOGES
C07K14/4711A61K38/1716A61K45/06C07K14/47C12N15/62G01N33/6896C07K2319/00C07K2319/30G01N2800/2821G01N2800/2828G01N2800/2835
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 12,291,552
App. No.
17/729,534
Granted
May 6, 2025
Kind
B2
Abstract

The present invention relates to a chimeric protein comprising at least one human amyloid P component and at least one fragment of an Fc region of a human antibody, the human amyloid P component and the fragment of an Fc region with which it is associated being bound to each other by means of a hinge region.

Claims (28)

1. A method for treating in an individual with systemic amyloidosis comprising administering an effective amount of a chimeric protein to the individual, wherein the chimeric protein comprises from N-terminal part to C-terminal part

(i) a human serum amyloid P compound (SAP);

(ii) a first hinge region;

(iii) a first Fc region of a human antibody;

(iv) a spacer chain;

(v) a second hinge region; and

(vi) a second Fc region of a human antibody;

wherein the chimeric protein is a single polypeptide chain comprising a functional dimeric Fc region.

2. The method of claim 1 , wherein the human SAP comprises an amino acid sequence having at least 80 % identity with the amino acid sequence set forth in SEQ ID NO: 1.

3. The method of claim 2 , wherein the SAP comprises the amino acid sequence set forth in SEQ ID NO:1.

4. The method of claim 1 , wherein the first Fc region and the second Fc region comprise an Fc region of an IgG1 antibody or an IgG2 antibody.

5. The method of claim 1 , wherein the first Fc region and the second Fc region comprise an Fc region of an IgG1 antibody.

6. The method of claim 1 , wherein the first Fc region comprises at least one amino acid sequence having at least 80% identity with the amino acid sequence set forth in SEQ ID NO:3.

7. The method of claim 1 , wherein the first Fc region and the second Fc region are identical.

8. The method of claim 1 , wherein the first Fc region and the second Fc region are not identical.

9. The method of claim 1 , wherein the first hinge region or second hinge region comprises an amino acid sequence having at least 80% identity with a sequence set forth in SEQ ID NOs: 13 or 15-19.

10. The method of claim 1 , wherein the first hinge region and the second hinge region are identical.

11. The method of claim 1 , wherein the first hinge region and the second hinge region are not identical.

12. The method of claim 1 , wherein the spacer chain comprises the amino acid sequence set forth in SEQ ID NO:5.

13. The method of claim 1 , wherein the spacer chain comprises the amino acid sequence set forth in SEQ ID NO: 5, GGGGS, repeated 3 times.

14. The method of claim 1 , wherein the chimeric protein is a monomeric SAP-ScFc.

15. The method of claim 1 , wherein the chimeric protein is administered via intravenous, subcutaneous, or intramuscular route.

16. The method of claim 1 , wherein the chimeric protein is recombinantly produced in a CHO cell, an SP2/0 cell, or a YB2/0 cell.

17. The method of claim 1 , wherein the individual is human.

18. The method of claim 1 , wherein the individual has AL amyloidosis.

19. The method of claim 1 , wherein the individual has AA amyloidosis.

20. The method of claim 1 , wherein the individual has ATTR amyloidosis.

21. The method of claim 1 , wherein the individual has amyloid deposits in the kidney.

Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 27, 2022
From: DE ROMEUF, CHRISTOPHE; SIRAC, CHRISTOPHE
To: LABORATOIRE FRANCAIS DU FRACTIONNEMENT ET DES BIOTECHNOLOGIES; CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (CNRS); UNIVERSITÉ DE LIMOGES
Reel/Frame 059744/0161 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 27, 2022
From: LABORATOIRE FRANCAIS DU FRACTIONNEMENT ET DES BIOTECHNOLOGIES
To: CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (CNRS); UNIVERSITÉ DE LIMOGES
Reel/Frame 059750/0005 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 27, 2022
From: BROUET, JEAN-CLAUDE
To: CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (CNRS); UNIVERSITÉ DE LIMOGES
Reel/Frame 059750/0044 →
Continuity (3)
Continuation 15977489 · May 11, 2018
Division 15032542
Related Publication 20220356219A1 · Nov 10, 2022
References Cited (64)
US 8808666B2 · Wall et al. · 2014 [cited by applicant]
US 9683017B2 · Wall et al. · 2017 [cited by applicant]
US 10046050B2 · Wall et al. · 2018 [cited by applicant]
US 10213506B2 · Wall et al. · 2019 [cited by applicant]
US 10308685B2 · Wall et al. · 2019 [cited by applicant]
US RE47838E · Wall et al. · 2020 [cited by applicant]
US 10646568B2 · Wall et al. · 2020 [cited by applicant]
US 11345730B2 · Romeuf et al. · 2022 [cited by applicant]
US 20080260738A1 · Moore et al. · 2008 [cited by applicant]
US 20090191196A1 · Pepys · 2009 [cited by applicant]
US 20090252729A1 · Farrington et al. · 2009 [cited by applicant]
US 20100317596A1 · Willett et al. · 2010 [cited by applicant]
US 20160264637A1 · Romeuf et al. · 2016 [cited by applicant]
US 20180298071A1 · De Romeuf et al. · 2018 [cited by applicant]
US 20220160831A1 · Pons · 2022 [cited by applicant]
FR 3012453A1 · 2015 [cited by applicant]
WO 199505394A1 · 1995 [cited by applicant]
WO 2002042462A2 · 2002 [cited by applicant]
WO 2006053301A2 · 2006 [cited by applicant]
WO 2008143954A2 · 2008 [cited by applicant]
WO 2009000926A1 · 2008 [cited by applicant]
WO 2010106180A2 · 2010 [cited by applicant]
WO 2010141918A1 · 2010 [cited by applicant]
WO 2010148234A1 · 2010 [cited by applicant]
WO 2011119608A1 · 2011 [cited by applicant]
WO 2013096847A1 · 2013 [cited by applicant]
WO 2015017548A2 · 2015 [cited by applicant]
WO 2015063728A1 · 2015 [cited by applicant]
WO 2016032949A1 · 2016 [cited by applicant]
WO 2019197651A1 · 2019 [cited by applicant]
WO 2022094630A1 · 2022 [cited by applicant]
Bharadwaj, D. et al. (Jun. 2001). “Serum Amyloid P Component Binds to Fcγ Receptors and Opsonizes Particles for Phagocytosis,” The Journal of Immunology 166(11):6735-6741. [cited by applicant]
Bodin, K. et al. (Nov. 4, 2010, e-pub. May 1, 2011). “Antibodies to Human Serum Amyloid P Component Eliminate Visceral Amyloid Deposits,” Nature 468(7320):93-97, 10 pages. [cited by applicant]
Czajkowsky, D.M. et al. (Oct. 2012).“Fc-Fusion Proteins: New Developments and Future Perspectives,” EMBO Mol. Med. 4(10):1015-1028. [cited by applicant]
International Search Report and Written Opinion of the Searching Authority mailed Mar. 16, 2015, for Patent Application No. PCT/IB2014/065734, filed Oct. 31, 2014, 20 pages. (English Translation). [cited by applicant]
Janeway Jr, C.A. et al. (2001). “The Structure of a Typical Antibody Molecule,” in Immunobiology: The Immune System in Health and Disease, 5th edition, Garland Science. [cited by applicant]
Lagassé, H.D. et al. (Jul. 2019). “Fc-Fusion Drugs Have Fcγr/C1q Binding and Signaling Properties That May Affect Their Immunogenicity,” The AAPS Journal 21(4):62, 10 pages. [cited by applicant]
Picken, M.M. (May 2007). “New Insights Into Systemic Amyloidosis: The Importance of Diagnosis of Specific Type,” Current Opinion In Nephrology and Hypertension 16(3):196-203. [cited by applicant]
Pilling, D. et al. (Oct. 16, 2018). “The Development of Serum Amyloid P as a Possible Therapeutic,” Frontiers in immunology 9:2328, 1-10. [cited by applicant]
Rosenzweig, M. (Dec. 2011). “Light Chain (AL) Amyloidosis: Update on Diagnosis and Management,” Journal of Hematology & Oncology 4(47):1-8. [cited by applicant]
Shoji-Hosaka, E. et al. (2006). “Enhanced Fc-Dependent Cellular Cytotoxicity of Fc Fusion Proteins Derived from TNF Receptor II and LFA-3 by Fucose Removal from Asn-Linked Oligosaccharides,” J. Biochem. 140(6):777-783. [cited by applicant]
Tennent, G.A. et al. (May 1995). “Serum Amyloid P Component Prevents Proteolysis of the Amyloid Fibrils of Alzheimer Disease and Systemic Amyloidosis,” Proceedings of the National Academy of Sciences 92(10):4299-4303. [cited by applicant]
Almagro, J.C. et al. (Jan. 4, 2018). “Progress and Challenges in the Design and Clinical Development of Antibodies for Cancer Therapy.” Front. Immunol. 8(1751):1-19. [cited by applicant]
Beierle, S.P. et al. (2016). “A Novel Murine Model of Light Chain Associated (AL) Amyloidosis For Validating Peptide Amyloid Imaging Agents—A SPECT/CT and Microautoradiography Study,” 2016 World Molecular Imaging Congre… [cited by applicant]
Cox, N. et al. (Aug. 15, 2014, e-pub. Aug. 15, 2015). “Distinct Fcγ Receptors Mediate the Effect of Serum Amyloid P on Neutrophil Adhesion and Fibrocyte Differentiation,” J. Immunol. 193(4):1701-1708, 24 pages. [cited by applicant]
Elliott, J.M. et al. (2014). “Antiparallel Conformation of Knob and Hole Aglycosylated Half-Antibody Homodimers Is Mediated by a CH2-CH3 Hydrophobic Interaction,” Journal of Molecular Biology 426:1947-1957. [cited by applicant]
Foster, J.S. et al. (Mar. 2017, e-pub. Mar. 1, 2018). “Preliminary Characterization of a Novel Peptide-Fc-Fusion Construct for Targeting Amyloid Deposits,” Amyloid 24(SUP1):26-27, 3 pages. [cited by applicant]
Lee, S. et al. (2013). “Dual Isotope SPECT Imaging of I-123 and I-125,” IEEE Medical Imaging Conference, Seoul, South Korea, Oct. 27-Nov. 2, 2013, 4 pages. [cited by applicant]
Liu, H. et al. (Jan. 26, 2017). “Fc Engineering for Developing Therapeutic Bispecific Antibodies and Novel Scaffolds,” Frontiers in Immunology 8(38):1-15. [cited by applicant]
Martin, E.B. et al. (2014). “Detection of Cardiac Amyloidosis by SPECT/CT Imaging Using Both 125I-Serum Amyloid P-Component and the Novel 125I-p5R+14 Peptide,” XIVth International Symposium on Amyloidosis, Indianapolis,… [cited by applicant]
Martin, E.B. et al. (Mar. 3, 2016). “Comparative Evaluation of p5+ 14 With SAP and Peptide p5 by Dual-Energy SPECT Imaging of Mice With AA Amyloidosis,” Scientific Reports 6(22695):1-10. [cited by applicant]
Morgan, G.J. et al. (2020). “The Process of Amyloid Formation Due to Monoclonal Immunoglobulins,” Hematology/ Oncology Clinics of North America 34(6):1041-1054. [cited by applicant]
Sirac, C. et al. (Nov. 5, 2021). “Pre-Clinical Characterization of a Novel Fusion Protein (AT-03), With Pan-Amyloid Binding and Removal,” Blood 138 (Suppl 1):1207, 2 pages. [cited by applicant]
Wall, J. et al. (May 2011). “The 99mTc-p31 Peptide Offers Enhanced Amyloid Imaging as Compared to SAP-A Quantitative Biodistribution and Dual Energy SPECT Imaging Study,” The Journal of Nuclear Medicine 52 (Suppl 1)228:… [cited by applicant]
Wall, J. S. et al. (2006). “Micro-Imaging of Amyloid in Mice,” Methods in Enzymology 412:161-182, 20 pages. [cited by applicant]
Wall, J.S. et al. (2010). “99mTc-Labeled Serum Amyloid P Component as a Tool for Evaluating Novel Amyloid Imaging Agents,” XII International Symposium on Amyloidosis, Rome, Italy, Apr. 18-21, 2010, P-103:140-141. [cited by applicant]
Wall, J.S. et al. (2010). “Rapid Dehalogenation of 124I-SAP in Mice Enhances the Specific Detection of Amyloid: A Dynamic microPET Imaging Study,” XII International Symposium on Amyloidosis, Rome, Italy, Apr. 18-21, 201… [cited by applicant]
Wall, J.S. et al. (2017, e-pub. Aug. 21, 2017). “Pretargeting Immunotherapy: A Novel Treatment Approach for Systemic Amyloidosis,” Pharmaceutical Patent Analyst 6(5):215-223. [cited by applicant]
Wall, J.S. et al. (2018, e-pub. Oct. 30, 2018). “Bifunctional Amyloid-Reactive Peptide Promotes Binding of Antibody 11-1F4 to Diverse Amyloid Types and Enhances Therapeutic Efficacy,” PNAS 115(46):E10839-E10848. [cited by applicant]
Wall, J.S. et al. (Aug. 2012). “Comparative Analysis of Peptide p5 and Serum Amyloid P Component for Imaging AA Amyloid in Mice Using Dual-Isotope SPECT,” Molecular Imaging and Biology 14(4):402-407, 1-13. [cited by applicant]
Wall, J.S. et al. (Dec. 2008). “Quantitative Tomography of Early-Onset Spontaneous AA Amyloidosis in Interleukin 6 Transgenic Mice,” Comparative Medicine 58(6):542-550. [cited by applicant]
Wall, J.S. et al. (Dec. 26, 2012). “AL Amyloid Imaging and Therapy With a Monoclonal Antibody to a Cryptic Epitope on Amyloid Fibrils,” PloS One 7(12):e52686, 10 pages. [cited by applicant]
Wall, J.S. et al. (Sep. 18, 2013). “Evaluation of SPECT Detection of Cardiac Amyloidosis in Mice by Using 125I-p5R+14 Peptide or 125I-SAP,” World Molecular Imaging Congress, Savannah, GA, Sep. 18-21, 2013, Poster Sessio… [cited by applicant]
Wall, J.S. et al. (Sep. 2005). “Quantitative High-Resolution Microradiographic Imaging of Amyloid Deposits in a Novel Murine Model of AA Amyloidosis,” Amyloid 12(3):149-156. [cited by applicant]