Desmoglein 2 (DSG2) binding proteins and uses therefor

Patent metadata

Field	Value
Publication number	US-12466859-B2
Application number	US-202318475950-A
Country	US
Kind code	B2
Filing date	Sep 27, 2023
Priority date	Sep 24, 2013
Publication date	Nov 11, 2025
Grant date	Nov 11, 2025

Abstract

Disclosed are recombinant adenoviral compositions and methods for their use in treating disorders associated with epithelial tissues.

First claim

We claim:

1 . A method for enhancing access to epithelial cells, the method comprising administering to a subject with a disorder associated with epithelial cells:
a) a cellular immunotherapy agent; and b) a recombinant AdB-⅔ fiber polypeptide, comprising:
one or more AdB-⅔ fiber polypeptide shaft domain motifs;
an AdB-⅔ fiber polypeptide knob domain operatively linked to and located C-terminal to the one or more AdB-⅔ fiber polypeptide shaft domain motifs,
wherein the AdB-⅔ fiber polypeptide knob domain comprises the peptide of SEQ ID NO: 4 wherein:
X2 is H, L, or P;
X3 is K or E;
X4 is T, F, S, or L;
X5 is V, or D;
X6 is E or G;
X7 is Y or F;
X8 is T, K, or E; and
X9 is N or S; and
wherein at least one of the following is true: X2 is P; X3 is E; X4 is S, or L; X5 is D; X6 is G; X7 is F; X8 is E; or X9 is S; and
one or more non-AdB-⅔-derived dimerization domains operatively linked to and located N-terminal to the one or more AdB-⅔ fiber polypeptide shaft domain motifs.

2 . The method of claim 1 , wherein the cellular immunotherapy agent comprises a T-cell or a dendritic cell.

3 . The method of claim 1 , wherein the disorder is selected from the group consisting of solid tumors, irritable bowel syndrome, inflammatory bowel disorder, Crohn's disease, ulcerative colitis, constipation, gastroesophageal reflux disease, Barrett's esophagus, chronic obstructive pulmonary disease, asthma, bronchitis, pulmonary emphysema, cystic fibrosis, interstitial lung disease, pneumonia, primary pulmonary hypertension, pulmonary embolism, pulmonary sarcoidosis, tuberculosis, pancreatitis, pancreatic duct disorders, bile duct obstruction, cholecystitis, choledocholithiasis, brain disorders, psoriasis, dermatitis, glomerulonephritis, hepatitis, diabetes, thyroid disorders, cellulitis, infection, pyelonephritis, and gallstones.

4 . The method of claim 1 , wherein the disorder associated with epithelial tissue is a solid tumor.

5 . The method of claim 4 , wherein the solid tumor is selected from the group consisting of breast tumors, lung tumors, colon tumors, rectal tumors, stomach tumors, prostate tumors, ovarian tumors, uterine tumors, skin tumors, endocrine tumors, cervical tumors, kidney tumors, melanomas, pancreatic tumors, liver tumors, brain tumors, bead and neck tumors, nasopharyngeal tumors, gastric tumors, squamous cell carcinomas, adenocarcinomas, bladder tumors, and esophageal tumors.

6 . The method of claim 1 , wherein the method further comprises administering an antibody, a nucleic acid, a chemotherapeutic agent, or a radioactive particle.

7 . The method of claim 6 , wherein the antibody comprises trastuzumab, cetumiximab, petuzumab, apomab, conatumumab, lexatumumab, bevacizumab, bevacizumab, denosumab, zanolimumab, lintuzumab, edrecolomab, rituximab, ticilimumab, tositumomab, alemtuzumab, epratuzumab, mitumomab, gemtuzumab ozogamicin, oregovomab, pemtumomab, daclizumab, panitumumab, catumaxomab, ofatumumab, or ibritumomab.

8 . The method of claim 6 , wherein the antibody selectively binds CTLA-4.

9 . The method of claim 6 , wherein the chemotherapeutic agent comprises docetaxel, doxorubicin, irinotecan, or paclitaxel.

10 . The method of claim 6 , wherein the chemotherapeutic agent comprises doxorubicin.

11 . The method of claim 6 , wherein the chemotherapeutic agent comprises PEGylated liposomal doxorubicin.

12 . The method of claim 1 , wherein the method further comprises administering an anti-inflammatory agent.

13 . The pharmaceutical composition of claim 12 , wherein the anti-inflammatory agent is conjugated to the recombinant AdB-⅔ fiber polypeptide.

14 . The method of claim 1 , wherein the method further comprises administering a corticosteroid.

15 . The method of claim 1 , wherein the method further comprises administering one or more of dexamethasone, prednisone, cyclophosphamide, pentostatin, rituximab, methotrexate, and vincristine.

16 . The method of claim 1 , wherein the AdB-⅔ fiber polypeptide knob domain comprises the peptide of any one of SEQ ID NOS: 5-11.

17 . The method of claim 1 , wherein the AdB-⅔ fiber polypeptide does not include an AdB-⅔ fiber polypeptide tail domain.

18 . The method of claim 1 , wherein each shaft domain motif is selected from the group consisting of an Ad3 fiber polypeptide shaft domain motif, an Ad7 fiber polypeptide shaft domain motif, an Ad11 fiber polypeptide shaft domain motif, an Ad14 fiber polypeptide shaft domain motif, an Ad14a fiber polypeptide shaft domain motif, and combinations thereof.

19 . The method of claim 1 , wherein the one or more AdB-⅔ fiber polypeptide shaft domain motifs comprise 1-22 shaft domain motifs.

20 . The method of claim 1 , wherein each shaft domain motif comprises an amino acid sequence selected from the group consisting of SEQ ID NOS: 43-48.

21 . The method of claim 1 , wherein the one or more shaft domain motifs are the shaft domain motif of SEQ ID NO: 43.

22 . The method of claim 1 , wherein the AdB-⅔ fiber polypeptide contains a single AdB-⅔ fiber polypeptide shaft domain motif.

23 . The method of claim 1 , wherein the dimerization domain comprises an amino acid sequence selected from the group consisting of EVSALEK (SEQ ID NO:24) and/or KVSALKE (SEQ ID NO: 25).

24 . The method of claim 1 , wherein the recombinant AdB-⅔ fiber polypeptide comprises the amino acid sequence selected from the group consisting of:

a) (M/-)

(SEQ ID NO: 28)

GSKVSALKEKVSALKEKVSALKEKVSALKEKVSALKEGSGGGSGGGSGG

GSNSIALKNNTLWTGPKPEANCIIEYGKQNPDSKLTLILVKNGGIVNGY

VTLMGASDYVNTLFKNKNVSINVELYFDATGHILPDSSSLKTDLELKYK

QTADFSARGFMPSTTAYPFVLPNAGTHNENFIFGQCYYKASDGALFPLE

VTVMLNKRLPDSRTSYVMTFLWSLNAGLAPETTQATLITSPFTFSYIRE

DD;

b) (M/-)

(SEQ ID NO: 29)

GSKVSALKEKVSALKEKVSALKEKVSALKEKVSALKEGSGGGSGGGSGG

GSNSIALKNNTLWTGPKPEANCIIEYGKQNPDSKLTLILVKNGGIVNGY

VTLMGASDYVNTLFKNKNVSINVELYFDATGHILPDSSSLKTDLEL

YKQTADSSARGFMPSTTAYPFVLPNAGTHNENYIFGQCYYKASDGALF

PLEVTVMLNKRLPDSRTSYVMTFLWSLNAGLAPETTQATLITSPFTFS

YIREDD;

c) (M/-)

(SEQ ID NO: 30)

GSKVSALKEKVSALKEKVSALKEKVSALKEKVSALKEGSGGGSGGGSG

GGSNSIALKNNTLWTGPKPEANCIIEYGKQNPDSKLTLILVKNGGIVN

Assignees

• Univ Washington Through Its Center For Commercialization

Inventors

• Lieber Andre
• Wang Hongjie

Classifications

• G01N2500/20

  cell-free systems · CPC title

• G01N2500/02

  Screening involving studying the effect of compounds C on the interaction between interacting molecules A and B (e.g. A = enzyme and B = substrate for A, or A = receptor and B = ligand for the receptor) · CPC title

• G01N33/94

  involving narcotics {or drugs or pharmaceuticals, neurotransmitters or associated receptors} · CPC title

• C12N2710/10033

  Use of viral protein as therapeutic agent other than vaccine, e.g. apoptosis inducing or anti-inflammatory · CPC title

• C12N2710/10022

  New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes · CPC title