IP Library › Granted Patent US 12,491,268
Granted Patent B2
US 12,491,268 · App. 17/819,180 · Granted Dec 9, 2025

Targeted protein contrast agents, methods of making, and uses thereof

Inventors: Jenny Jie Yang (Atlanta, GA); Fan Pu (Atlanta, GA); Shenghui Xue (Atlanta, GA); Jingjuan Qiao (Atlanta, GA); Shanshan Tan (Atlanta, GA); Mani Salarian (Atlanta, GA)
Assignee: Georgia State University Research Foundation, Inc.
A61K49/143A61K49/126A61K49/16C01G99/006C07K14/76C07K2319/32C07K2319/33C07K2319/70
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 12,491,268
App. No.
17/819,180
Granted
Dec 9, 2025
Kind
B2
Abstract

Provided herein are protein contrast agents and targeted protein contrast agents, formulations thereof, and methods of use, including but not limited to, as a magnetic resonance imaging contrast agent.

Claims (24)

1 . A protein contrast agent comprising:

a parvalbumin polypeptide, wherein the parvalbumin polypeptide has the amino acid sequence comprising SEQ ID NO: 10; and

a HER2 or HER1/EGFR targeting moiety directly fused or indirectly linked via a peptide linker to a terminus of the parvalbumin polypeptide.

2 . The protein contrast agent of claim 1 , wherein the targeting moiety is a HER2 targeting moiety.

3 . The protein contrast agent of claim 2 , wherein the HER2 targeting moiety is a HER2-specific affibody.

4 . The protein contrast agent of claim 1 , wherein the targeting moiety is a HER1/EGFR targeting moiety.

5 . The protein contrast agent of claim 4 , wherein the HER1/EGFR targeting moiety is a HER1/EGFR-specific affibody.

6 . The protein contrast agent of claim 1 , wherein the targeting moiety has a sequence according to SEQ ID NO: 54 or SEQ ID NO: 55.

7 . The protein contrast agent of claim 6 , wherein the targeting moiety has a sequence according to SEQ ID NO: 54.

8 . The protein contrast agent of claim 6 , wherein the targeting moiety has a sequence according to SEQ ID NO: 55.

9 . The protein contrast agent of claim 1 , wherein the targeting moiety is directly fused or indirectly linked via the peptide linker to the C-terminus, N-terminus, or both the C-terminus and the N-terminus of the parvalbumin polypeptide.

10 . The protein contrast agent of claim 1 , wherein the targeting moiety is directly fused or indirectly linked via the peptide linker to the C terminus of the parvalbumin polypeptide.

11 . The protein contrast agent of claim 1 , wherein the targeting moiety is directly fused or indirectly linked via the peptide linker to one or more amino acids between the C terminus and the N terminus of the parvalbumin polypeptide.

12 . The protein contrast agent of claim 1 , further comprising a paramagnetic ion, wherein the paramagnetic ion is directly bound to at least one amino acid of the parvalbumin polypeptide.

13 . The protein contrast agent of claim 12 , wherein the paramagnetic ion is Gd 3+ .

14 . The protein contrast agent of claim 1 , wherein the protein contrast agent is PEGylated.

15 . The protein contrast agent of claim 1 , wherein the hydrophobicity of the protein contrast agent is altered via an insertion, deletion, or substitution of an amino acid in the protein contrast agent.

16 . The protein contrast agent of claim 1 , wherein the hydrophilicity of the protein contrast agent is altered via insertion, deletion, or substitution of an amino acid in the protein contrast agent.

17 . A pharmaceutical composition comprising:

a protein contrast agent according to claim 1 ; and

a pharmaceutically acceptable carrier.

18 . A method of using a protein contrast agent for magnetic resonance imaging (MRI) of a subject in need thereof, comprising:

administering an effective amount of the protein contrast agent according to claim 1 to the subject; and

imaging at least a portion of the subject using MRI magnetic resonance imaging.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 7, 2023
From: YANG, JENNY JIE; PU, FAN; XUE, SHENGHUI; QIAO, JINGJUAN; TAN, SHANSHAN; SALARIAN, MANI
To: GEORGIA STATE UNIVERSITY RESEARCH FOUNDATION, INC.
Reel/Frame 064505/0563 →
Continuity (4)
Continuation 17015633 · Sep 9, 2020
Division 15572863
Provisional Application 62159685 · May 11, 2015
Related Publication 20230057249A1 · Feb 23, 2023
References Cited (31)
US 9956304B2 · Yang et al. · 2018 [cited by applicant]
US 10814020B2 · Yang · 2020 [cited by examiner]
US 10849993B2 · Yang et al. · 2020 [cited by applicant]
US 11419954B2 · Yang · 2022 [cited by examiner]
US 11426471B2 · Yang · 2022 [cited by examiner]
US 20030220482A1 · Huang et al. · 2003 [cited by applicant]
US 20050250700A1 · Sato et al. · 2005 [cited by applicant]
US 20090274625A1 · Denmeade et al. · 2009 [cited by applicant]
WO 2007081751A2 · 2007 [cited by applicant]
WO 2009146099A2 · 2009 [cited by applicant]
WO 2013184786A2 · 2013 [cited by applicant]
Xue, Georgia State University ScholarWorks@Georgia State University, Biology Dissertation, “Design of Novel Protein-based MRI Contrast Agents with High Relaxivity and Stability for Biomedical Imaging”, 334 pages (Year: … [cited by examiner]
Qiao et al, PLoS One, vol. 6, Issue 3, e18103, pp. 1-9 (Year: 2011). [cited by examiner]
Non-Final Office Action of U.S. Appl. No. 17/015,571, mailed Dec. 29, 2021, 11 pages. [cited by applicant]
International Search Report and Written Opinion issued for PCT/US2016/031900 mailed Oct. 28, 2016. [cited by applicant]
Yang et al., “Rational Design of Protein-based MRI Contrast Agents.” JACS. (2008) 130:92670-9267. [cited by applicant]
Yang et al., “Rational Design of a Calcium-Binding Protein.” JACS. (2003) 125:6165-6171. [cited by applicant]
Li et al., “Rational design of a conformation-switchable Ca2+ and Tb3+ -binding protein without the use of multiple coupled metal-binding sites.” FEBS. (2008) 275:5048-5061. [cited by applicant]
Li et al., “PEGylation of Protein-based MRI Contrast Agents Improves Relaxivities and Biocompatibilities.” J. Inorg. Biochem. (2012) 107:111-118. [cited by applicant]
Xue et al., “Design of a novel class of protein-based magnetic resonance imaging contrast agents for the molecular imaging of cancer biomarkers.” Interdiscip. Rev. Nanomed. Nanobiotechnol. (2013) 5(2):163-179. [cited by applicant]
Xue et al., “Design of ProCAs (Protein-based Gd3+ MRI Contrast Agents) with High Dose Efficiency and Capability for Molecular Imaging of Cancer Biomarkers.” Medicinal Res. Rev. (2014) 34:1070-1099. [cited by applicant]
Pfuhl et al., “NMR exchange broadening arising from specific low affinity protein self-association: Analysis of nitrogen-15 nuclear relaxation for rat CO2 domain 1.” J. Biomol. NMR (1999) 14(4):307-320. [cited by applicant]
Davis et al., “The role of charge residues mediating low affinity protein-protein recognition at the cell surface by CO2.” PNAS (1998) 95(10):5490-5494. [cited by applicant]
Evans et al., “Crystal Structure and Binding Properties of the CO2 and CD244 (2B4)-binding Protein CD48.” J. Biol. Chem. (2006) 281(39):29309-29320. [cited by applicant]
Luo et al., “Structure-Function Study and Anti-HIV Activity of Synthetic Peptide Analogues Derived from Viral Chemokine vMIP-11.” Biochem. (2000) 39:13545-13550. [cited by applicant]
Qiao et al, “Molecular imaging of EGFR/HER2 cancer biomarkers by protein MRI contrast agents.” J. Biol. Inorg. Chem. (2014) 19(2): 259-270. [cited by applicant]
European Search Report mailed on Nov. 26, 2018 for Application No. 16793465.2. [cited by applicant]
Shenghui Xue; et al: “Protein MRI contrast agent with unprecedented metal selectivity and sensitivity for liver cancer imaging”, Proceedings of the National Academy of Sciences of the United Stated of America, vol. 112,… [cited by applicant]
Shen, et al., “Evaluation of Phage Display Discovered Peptides as Ligands for Prostate-Specific Membrane Antigen (PSMA),” PLoS One, 2013, pp. 1-10, vol. 8, No. 7, doi: 10.1371/journal.pone.0068339. [cited by applicant]
Office Action issued for Canadian Application No. 2985075, dated May 6, 2022. [cited by applicant]
Reddy Chichili, V.P. et al. Linkers in the structural biology of protein-protein interactions. Protein Sci. 22(2):153-167 (Feb. 2013). [cited by applicant]