Desmoglein 2 (DSG2) binding proteins and uses therefor

Patent metadata

Field	Value
Publication number	US-9688727-B2
Application number	US-201414429803-A
Country	US
Kind code	B2
Filing date	Sep 24, 2014
Priority date	Sep 24, 2013
Publication date	Jun 27, 2017
Grant date	Jun 27, 2017

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 recombinant AdB-2/3 fiber polypeptide, comprising:
(a) one or more AdB-2/3 fiber polypeptide shaft domain motifs;
(b) 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 SEQ ID NO:4 TLWTGPKPEA NCIIEYGKQN PDSKLTLILV KNGG(I/L)VNGYV TLMGASDYVN TLFKNKNVSI NVELYFDATG HILPDSSSLK TDLEX2 X3YKQTAD X4 SARGFMP STTAYPFX5LP NAGTHNX6NX7 IFGQCYY X8 ASDGALFPLEVTV MLNKRLPDSR TSYVMTFLWS LX9AGLAPETT QATLITSPFT FSYIREDD (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
(c) 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.

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

3. The recombinant AdB-2/3 fiber polypeptide 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.

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

5. The recombinant AdB-2/3 fiber polypeptide of claim 1 , wherein each shaft domain motif comprises an amino acid sequence selected from the group consisting of SEQ ID NOS: 43-48.

6. The recombinant AdB-2/3 fiber polypeptide 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).

7. The recombinant AdB-2/3 fiber polypeptide of claim 1 , wherein the one or more shaft domain motifs are the shaft domain motif of SEQ ID NO:43.

8. The recombinant AdB-2/3 fiber polypeptide of claim 1 , comprising the amino acid sequence of

(a)

(SEQ ID NO: 28)

(M/)GSKVSALKEKVSALKEKVSALKEKVSALKEKVSALKEGSGGGSGGG

SGGGSNSIALKNNTLWTGPKPEANCIIEYGKQNPDSKLTLILVKNGGIVN

GYVTLMGASDYVNTLFKNKNVSINVELYFDATGHILPDSSSLKTDLELKY

KQTADFSARGFMPSTTAYPFVLPNAGTHNENFIFGQCYYKASDGALFPLE

VTVMLNKRLPDSRTSYVMTFLWSLNAGLAPETTQATLITSPFTFSYIRED

D;

(b)

(SEQ ID NO: 29)

(M/)GSKVSALKEKVSALKEKVSALKEKVSALKEKVSALKEGSGGGSGGG

SGGGSNSIALKNNTLWTGPKPEANCIIEYGKQNPDSKLTLILVKNGGIVN

GYVTLMGASDYVNTLFKNKNVSINVELYFDATGHILPDSSSLKTDLELEY

KQTADSSARGFMPSTTAYPFVLPNAGTHNENYIFGQCYYKASDGALFPLE

VTVMLNKRLPDSRTSYVMTFLWSLNAGLAPETTQATLITSPFTFSYIRED

D;

(c)

(SEQ ID NO: 30)

(M/-)GSKVSALKEKVSALKEKVSALKEKVSALKEKVSALKEGSGGGSGG

GSGGGSNSIALKNNTLWTGPKPEANCIIEYGKQNPDSKLTLILVKNGGIV

NGYVTLMGASDYVNTLFKNKNVSINVELYFDATGHILPDSSSLKTDLELK

YKQTADFSARGFMPSTTAYPFVLPNAGTHNENYIFGQCYYKASDGALFPL

EVTVMLNKRLPDSRTSYVMTFLWSLSAGLAPETTQATLITSPFTFSYIRE

DD;

(d)

(SEQ ID NO: 31)

(M/-)GSKVSALKEKVSALKEKVSALKEKVSALKEKVSALKEGSGGGSGG

GSGGGSNSIALKNNTLWTGPKPEANCIIEYGKQNPDSKLTLILVKNGGIV

NGYVTLMGASDYVNTLFKNKNVSINVELYFDATGHILPDSSSLKTDLELK

YKQTADFSARGFMPSTTAYPFDLPNAGTHNENYIFGQCYYKASDGALFPL

EVTVMLNKRLPDSRTSYVMTFLWSLNAGLAPETTQATLITSPFTFSYIRE

DD;

(e)

(SEQ ID NO: 32)

(M/-)GSKVSALKEKVSALKEKVSALKEKVSALKEKVSALKEGSGGGSGG

GSGGGSNSIALKNNTLWTGPKPEANCIIEYGKQNPDSKLTLILVKNGGIL

VNGYVTLMGASDYVNTLFKNKNVSINVELYFDATGHILPDSSSLKTDLEP

KYKQTADFSARGFMPSTTAYPFVLPNAGTHNENYIFGQCYYFASDGALFP

LEVTVMLNKRLPDSRTSYVMTFLWSLNAGLAPETTQATLITSPFTFSYIR

EDD;

(F)

(SEQ ID NO: 33)

(M/-)GSKVSALKEKVSALKEKVSALKEKVSALKEKVSALKEGSGGGSGG

GSGGGSNSIALKNNTLWTGPKPEANCIIEYGKQNPDSKLTLILVKNGGIV

NGYVTLMGASDYVNTLFKNKNVSINVELYFDATGHILPDSSSLKTDLELK

YKQTADLSARGFMPSTTAYPFVLPNAGTHNENYIFGQCYYKASDGALFPL

EVTVMLNKRLPDSRTSYVMTFLWSLNAGLAPETTQATLITSPFTFSYIRE

DD; 

and/or

(g)

(SEQ ID NO: 34)

(M/-)GSKVSALKEKVSALKEKVSALKEKVSALKEKVSALKEGSGGGSGG

GSGGGSNSIALKNNTLWTGPKPEANCIIEYGKQNPDSKLTLILVKNGGIV

NGYVT

Assignees

• Univ Washington Through Its Center For Commercialization
• Univ Washington

Inventors

• Lieber Andre
• Wang Hongjie

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P9/12

  Antihypertensives · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P31/06

  for tuberculosis · CPC title