IP Library Granted Patent US 12,371,461
Granted Patent B2
US 12,371,461 · App. 17/723,921 · Granted Jul 29, 2025

Nemo coiled coil mimics and methods of using same

Inventors: Paramjit S. Arora (Cold Spring Harbor, NY); Ethel Cesarman (Jersey City, NJ); Michael G. Wuo (Brooklyn, NY); Jouliana Sadek (Roosevelt Island, NY)
Assignees: NEW YORK UNIVERSITY; CORNELL UNIVERSITY
C07K14/4702A61K47/65A61P35/00C07C49/04C07K7/02C07K7/08A61K38/00A61K45/06
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 12,371,461
App. No.
17/723,921
Granted
Jul 29, 2025
Kind
B2
Abstract

This invention relates to macrostructures (and pharmaceutical formulations containing them) that include a parallel coiled-coil structure, wherein the parallel coiled-coil comprises a first coil of Formula I and a second coil of Formula II: T 1 -f 0 -g 0 -a 1 -b 1 -c 1 -d 1 -e 1 -f 1 -g 1 -a 2 -b 2 -c 2 -d 2 -e 2 -f 2 -g 2 -a 3 -b 3 -c 3 -d 3 -e 3 -T 2   (I) T 3 -g′ 0 -a′ 1 -b′ 1 -c′ 1 -d′ 1 -e′ 1 -f′ 1 -g′ 1 -a′ 2 -b′ 2 -c′ 2 -d′ 2 -e′ 2 -f′ 2 -g′ 2 -a′ 3 -b′ 3 -c′ 3 -d′ 3 -e′ 3 -f′ 3 -T 4   (II), as described in the present application. Methods of using these macrostructures are also disclosed.

Claims (11)

1. A method of inhibiting interaction between NEMO and a target molecule that binds to a helix dimer consisting of HLX1 and HLX2 of NEMO, said method comprising:

contacting NEMO and/or the target molecule with a macrostructure comprising a parallel coiled-coil selected from the group consisting of CHD1 NEMO , CHD2 NEMO , CHD3 NEMO , and CHD4 NEMO under conditions effective to inhibit interaction between NEMO and the target molecule, wherein the target molecule is vFLIP.

2. The method of claim 1 , wherein said contacting is carried out in vivo.

3. The method of claim 1 , wherein said contacting is carried out in a cell.

4. The method of claim 1 , wherein said contacting is carried out in a subject.

5. The method of claim 3 , wherein said contacting induces apoptosis of the cell, inhibits proliferation of the cell, and/or inhibits NFκB translocation in the cell.

6. The method of claim 3 , wherein the cells are mammalian cells.

7. The method of claim 3 , wherein the cells are primate cells.

8. The method of claim 3 , wherein the cells are lymphoma cells or Kaposi sarcoma (“KS”) cells.

9. The method of claim 1 , wherein the method is carried out in a subject.

10. The method of claim 1 , wherein the macrostructure comprising the parallel coiled-coil is CHD3 NEMO .

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 28, 2025
From: ARORA, PARAMJIT S.; WUO, MICHAEL G.
To: NEW YORK UNIVERSITY
Reel/Frame 070659/0220 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 28, 2025
From: CESARMAN, ETHEL; SADEK, JOULIANA
To: CORNELL UNIVERSITY
Reel/Frame 070672/0471 →
Continuity (3)
Continuation 16684082 · Nov 14, 2019
Provisional Application 62768373 · Nov 16, 2018
Related Publication 20220289802A1 · Sep 15, 2022
References Cited (38)
US 10851133B2 · Arora et al. · 2020 [cited by applicant]
US 11440938B2 · Arora et al. · 2022 [cited by applicant]
US 11891422B2 · Arora · 2024 [cited by examiner]
US 20180162907A1 · Arora et al. · 2018 [cited by applicant]
US 20200190155A1 · Arora et al. · 2020 [cited by applicant]
WO 9916883A2 · 1999 [cited by applicant]
WO 2016201007A1 · 2016 [cited by applicant]
Del Rizzo et al., “ATP Synthase b Subunit Dimerization Domain: A Right-Handed Coiled Coil with Offset Helices,” J. Mol. Biol. 364:735-46 (2006). [cited by applicant]
European Patent Application No. 16808232.9, Examination Report (Aug. 27, 2020). [cited by applicant]
Hodges, “De Novo Design of Alpha-Helical Proteins: Basic Research to Medical Applications, ” Biochem. Cell Biol. 74:133-54 (1996). [cited by applicant]
Holub & Kirshenbaum, “Tricks with Clicks: Modification of Peptidomimetic Oligomers via Copper-Catalyzed Azide-Alkyne [3 + 2] Cycloaddition,” Chem. Soc. Rev. 39:1325-37 (2010). [cited by applicant]
Monera et al., “Comparison of Antiparallel and Parallel Two-Stranded Alpha-Helical Coiled-Coils: Design, Synthesis, and Characterization,” J. Biol. Chem. 268(26):19218-27 (1993). [cited by applicant]
Zhou et al., “Disulfide Bond Contribution to Protein Stability: Positional Effects of Substitution in the Hydrophobic Core of the Two-Stranded Alpha-Helical Coiled-Coil,” Biochemistry 32:3178-87 (1993). [cited by applicant]
Examination Report for European Application No. 16808232.9 (dated May 27, 2022). [cited by applicant]
Hadley et al., “Preferred Side-Chain Constellations at Antiparallel Coiled-Coil Interfaces,” PNAS 105(2):530-35 (2008). [cited by applicant]
Hadley et al., “Preferred Side-Chain Constellations at Antiparallel Coiled-Coil Interfaces,” PNAS 105(2):530 (2008), Supporting Information (pp. 1-29), May 3, 2024. [cited by applicant]
Keating et al., “Side-Chain Repacking Calculations for Predicting Structures and Stabilities of Heterodimeric Coiled Coils,” PNAS 98(26):14825-30 (2001). [cited by applicant]
Keating et al., “Side-Chain Repacking Calculations for Predicting Structures and Stabilities of Heterodimeric Coiled Coils,” PNAS 98(26):14825 (2001), Supporting Information (pp. 1-4). [cited by applicant]
Mason et al., “Semirational Design of Jun-Fos Coiled Coils with Increased Affinity: Universal Implications for Leucine Zipper Prediction and Design,” PNAS 103(24):8989-94 (2006). [cited by applicant]
Mason et al., “Semirational Design of Jun-Fos Coiled Coils with Increased Affinity: Universal Implications for Leucine Zipper Prediction and Design,” PNAS 103(24):8989-94 (2006), Supporting Information (pp. 1-7). [cited by applicant]
Oberoi et al., “Structural Basis for the Assembly of the SMRT/NCoR Core Transcriptional Repression Machinery,” Nat. Struct. Mol. Biol. 18(2): 177-84 (2011) (Europe PMC Funders Author Manuscript Version). [cited by applicant]
Oberoi et al., “Structural Basis for the Assembly of the SMRT/NCoR Core Transcriptional Repression Machinery,” Nat. Struct. Mol. Biol. 18(2):177 (2011), Supplementary Material (pp. 1-8). [cited by applicant]
PCT/US2016/036531, International Search Report and Written Opinion (Oct. 6, 2016). [cited by applicant]
Poster, Wuo & Arora, “An Effective Strategy for Stabilizing Minimal Coiled-Coil Mimetics,” presented at Albany 2015: Conversation 19 (Jun. 9, 2015). [cited by applicant]
Poster, Wuo & Arora, “Short, Stabilized Coiled Coils as Potential Modulators of Protein-Mediated Interactions,” presented at the New York Academy of Sciences (Sep. 15, 2014). [cited by applicant]
Wuo et al., “An Effective Strategy for Stabilizing Minimal Coiled Coil Mimetics,” J. Am. Chem. Soc. 137:11618-21 (2015). [cited by applicant]
Wuo et al., “An Effective Strategy for Stabilizing Minimal Coiled Coil Mimetics,” J. Am. Chem. Soc. 137:11618 (2015), Supporting Information (pp.S1-S23). [cited by applicant]
PCT/US2016/36531, International Preliminary Report on Patentability (Dec. 21, 2017). [cited by applicant]
U.S. Appl. No. 15/580,987, Restriction Requirement and Election of Species (Jan. 11, 2019). [cited by applicant]
U.S. Appl. No. 15/580,987, Restriction Requirement and Election of Species (Jul. 25, 2019). [cited by applicant]
U.S. Appl. No. 15/580,987, Office Action Dated Nov. 27, 2019. [cited by applicant]
European Patent Application No. 16808232.9, Supplementary European Search Report (Jan. 22, 2019). [cited by applicant]
Horne et al., “Heterocyclic Peptide Backbone Modifications in an α-Helical Coiled Coil,” J. Am. Chem. Soc. 126:15366-15367 (2004). [cited by applicant]
Sun et al., “A Stable Transcription Factor Complex Nucleated by Oligomeric AML1-ETO Controls Leukaemogenesis,” Nature 500:93-98 (2013). [cited by applicant]
Betts, “Amino Acid Properties and Consequences of Substitutions,” Bioinformatics for Geneticists, Chapter 14, pp. 289-316 (2003). [cited by applicant]
Bagneris, “Crystal Structure of a vFlip-IKKg Complex: Insights into Viral Activation of the IKK Signalosome,” Molecular Cell 30:620-631 (2008). [cited by applicant]
Watkins, “Protein-Protein Interactions Mediated by Helical Tertiary Structure Motifs,” JACS 137:11622-11630 (2015). [cited by applicant]
Office Action in U.S. Appl. No. 16/684,082, mailed Jan. 19, 2022. [cited by applicant]