Desmoglein 2 (DSG2) binding proteins and uses therefor

Patent metadata

Field	Value
Publication number	US-11820795-B2
Application number	US-202117559391-A
Country	US
Kind code	B2
Filing date	Dec 22, 2021
Priority date	Sep 24, 2013
Publication date	Nov 21, 2023
Grant date	Nov 21, 2023

Abstract

The present invention provides recombinant adenoviral compositions and methods for their use in treating disorders associated with epithelial tissues.

First claim

We claim:

1. A pharmaceutical composition, comprising:
a) a first therapeutic agent, wherein the first therapeutic agent comprises a recombinant AdB-2/3 fiber polypeptide, comprising:
1) one or more AdB-2/3 fiber polypeptide shaft domain motifs;
2) an AdB-2/3 fiber polypeptide knob domain operatively linked to and located C-terminal to the one or more AdB-2/3 fiber polypeptide shaft domain motifs, wherein the AdB-2/3 fiber polypeptide knob domain comprises the peptide of any one of SEQ ID NOS: 5-11; and
3) one or more non-AdB-2/3-derived dimerization domains operatively linked to and located N-terminal to the one or more AdB-2/3 fiber polypeptide shaft domain motifs;

b) a second therapeutic agent; and
c) a pharmaceutically acceptable carrier.

2. The pharmaceutical composition of claim 1 , wherein the second therapeutic agent is a corticosteroid.

3. The pharmaceutical composition of claim 1 , wherein the second therapeutic agent is selected from dexamethasone, prednisone, cyclophosphamide, pentostatin, rituximab, methotrexate, and vincristine.

4. The pharmaceutical composition of claim 1 , wherein the second therapeutic agent is an anti-tumor therapeutic.

5. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is formulated for oral administration.

6. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is formulated for intravenous administration.

7. The pharmaceutical composition of claim 1 , wherein the AdB-2/3 fiber polypeptide does not include an AdB-2/3 fiber polypeptide tail domain.

8. The pharmaceutical composition 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 Ad 14 fiber polypeptide shaft domain motif, an Ad14a fiber polypeptide shaft domain motif, and combinations thereof.

9. The pharmaceutical composition of claim 1 , wherein the one or more AdB-2/3 fiber polypeptide shaft domain motifs comprise 1-22 shaft domain motifs.

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

11. The pharmaceutical composition 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).

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

13. The pharmaceutical composition of claim 1 , comprising the amino acid sequence selected from the group consisting of:

a) (M/-)

(SEQ ID NO: 28)

GSKVSALKEKVSALKEKVSALKEKVSALKEKVSALKEGSGGGSGGGSGG

GSNSIALKNNTLWTGPKPEANCIIEYGKQNPDSKLTLILVKNGGIVNGY

VTLMGASDYVNTLFKNKNVSINVELYFDATGHILPDSSSLKTDLELKYK

QTADFSARGFMPSTTAYPFVLPNAGTHNEN FIFGQCYYKASDGALFPL

EVTVMLNKRLPDSRTSYVMTFLWSLNAGLAPETTQATLITSPFTFSYIR 

EDD;

b) (M/-)

(SEQ ID NO: 29)

GSKVSALKEKVSALKEKVSALKEKVSALKEKVSALKEGSGGGSGGGSGG

GSNSIALKNNTLWTGPKPEANCIIEYGKQNPDSKLTLILVKNGGIVNGY

VTLMGASDYVNTLFKNKNVSINVELYFDATGHILPDSSSLKTDLEL YK

QTADSSARGFMPSTTAYPFVLPNAGTHNENYIFGQCYYKASDGALFPLE

VTVMLNKRLPDSRTSYVMTFLWSLNAGLAPETTQATLITSPFTFSYIRE 

DD;

c) (M/-)

(SEQ ID NO: 30)

GSKVSALKEKVSALKEKVSALKEKVSALKEKVSALKEGSGGGSGGGSGG

GSNSIALKNNTLWTGPKPEANCIIEYGKQNPDSKLTLILVKNGGIVNGY

VTLMGASDYVNTLFKNKNVSINVELYFDATGHILPDSSSLKTDLELKYK

QTADFSARGFMPSTTAYPFVLPNAGTHNENYIFGQCYYKASDGALFPLE

VTVMLNKRLPDSRTSYVMTFLWSL AGLAPETTQATLITSPFTFSYIRE 

DD;

d) (M/-)

(SEQ ID NO: 31)

GSKVSALKEKVSALKEKVSALKEKVSALKEKVSALKEGSGGGSGGGSGG

GSNSIALKNNTLWTGPKPEANCIIEYGKQNPDSKLTLILVKNGGIVNGY

VTLMGASDYVNTLFKNKNVSINVELYFDATGHILPDSSSLKTDLELKYK

QTADFSARGFMPSTTAYPF LPNAGTHNENYIFGQCYYKASDGALFPLE

VTVMLNKRLPDSRTSYVMTFLWSLNAGLAPETTQATLITSPFTFSYIRE 

DD;

e) (M/-)

(SEQ ID NO: 32)

GSKVSALKEKVSALKEKVSALKEKVSALKEKVSALKEGSGGGSGGGSGG

GSNSIALKNNTLWTGPKPEANCIIEYGKQNPDSKLTLILVKNGG VNGY

VTLMGASDYVNTLFKNKNVSINVELYFDATGHILPDSSSLKTDLE KYK

QTADFSARGFMPSTTAYPFVLPNAGTHNENYIFGQCYY ASDGALFPLE

VTVMLNKRLPDSRTSYVMTFLWSLNAGLAPETTQATLITSPFTFSYIRE 

DD;

f)(M/-)

(SEQ ID NO: 33)

GSKVSALKEKVSALKEKVSALKEKVSALKEKVSALKEGSGGGSGGGSGG

GSNSIALKNNTLWTGPKPEANCIIEYGKQNPDSKLTLILVKNGGIVNGY

VTLMGASDYVNTLFKNKNVSINVELYFDATGHILPDSSSLKTDLELKYK

QTAD SARGFMPSTTAYPFVLPNAGTHNENYIFGQCYYKASDGALFPLE

VTVMLNKRLPDSRTSYVMTFLWSLNAGLAPETTQATLITSPFTFSYIRE

DD;

Assignees

• Univ Washington Through Its Center For Commercialization
• Univ Washington

Inventors

• Lieber Andre
• Wang Hongjie

Classifications

• C12N15/86

  Viral vectors · CPC title

• C12N15/10

  Processes for the isolation, preparation or purification of DNA or RNA (chemical preparation of DNA or RNA C07H21/00; preparation of non-structural polynucleotides from microorganisms or with enzymes C12P19/34) · CPC title

• C12N7/00

  Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof (preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00) · CPC title

• C12N5/0652

  Cells of skeletal and connective tissues; Mesenchyme · CPC title

• C07K14/005 Primary

  from viruses · CPC title