US2016039904A1PendingUtilityA1

Stabilized single human cd4 domains and fusion proteins

Assignee: US HEALTHPriority: Mar 15, 2013Filed: Mar 12, 2014Published: Feb 11, 2016

Est. expiryMar 15, 2033(~6.6 yrs left)· nominal 20-yr term from priority

Inventors:Dimiter S. Dimitrov Weizao Chen Prabakaran Ponraj

C07K 2319/00A61K 38/00C07K 2319/33A61K 47/6425A61K 38/162A61K 38/1774C07K 2319/30C07K 14/70514C07K 16/1145C07K 16/1063A61K 47/48276

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References

Claims

Abstract

The invention provides a polypeptide comprising a single domain CD4, as well a fusion protein comprising the single domain CD4 and one or more fusion partners. A nucleic acid encoding the polypeptide or fusion protein, as well as compositions or cells comprising the polypeptide, fusion protein, or nucleic acid also are provided.

Claims

exact text as granted — not AI-modified

1 . A polypeptide comprising the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2. 
     
     
         2 . A composition comprising the polypeptide of  claim 1  and a carrier. 
     
     
         3 . A fusion protein comprising (i) the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2 and (ii) one or more fusion partners, wherein the one or more fusion partners optionally is fused to the amino acid sequence of (i) via a linker. 
     
     
         4 . (canceled) 
     
     
         5 . The fusion protein of  claim 3 , wherein the one or more fusion partners is an engineered antibody domain (eAd), an HIV envelope glycoprotein, an Fc region or portion thereof, an immunoglobulin heavy chain constant region, an immunoglobulin light chain constant region, or a combination thereof. 
     
     
         6 . (canceled) 
     
     
         7 . The fusion protein of  claim 5 , wherein the one or more fusion partners is an eAd and the eAd binds to an HIV envelope glycoprotein. 
     
     
         8 . The fusion protein of  claim 7 , wherein the eAd comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 12-16. 
     
     
         9 . (canceled) 
     
     
         10 . The fusion protein of  claim 5 , wherein the one or more fusion partners is an HIV envelope glycoprotein and the HIV envelope glycoprotein is gp120. 
     
     
         11 .- 12 . (canceled) 
     
     
         13 . A fusion protein comprising:
 A-(optional linker)-C-(optional linker)-B   or   B-(optional linker)-D-(optional linker)-E-(optional linker)-B   
       wherein A is an antibody or antibody fragment, B is the polypeptide of  claim 1 , C is an immunoglobulin light chain constant region, D is an immunoglobulin heavy chain constant region, and E is an Fc region or portion thereof. 
     
     
         14 . The fusion protein of  claim 13 , wherein the antibody or antibody fragment of A comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 12-16. 
     
     
         15 . The fusion protein of claim  12 , wherein the Fc region or portion thereof is an IgG1 Fc region. 
     
     
         16 . The fusion protein of  claim 15 , wherein the Fc region or portion thereof comprises SEQ ID NO: 7 or SEQ ID NO: 8. 
     
     
         17 . The fusion protein of  claim 3 , wherein the linker comprises one or more G 4 S motifs. 
     
     
         18 . The fusion protein of  claim 3 , wherein the linker comprises the amino acid sequence of SEQ ID NO: 9, SEQ ID NO: 10, or SEQ ID NO: 11. 
     
     
         19 . A composition comprising the fusion protein of  claim 3  and a carrier. 
     
     
         20 . A nucleic acid encoding the polypeptide of  claim 1 . 
     
     
         21 . A nucleic acid encoding the fusion protein of  claim 3 . 
     
     
         22 . A recombinant vector comprising the nucleic acid of  claim 20 . 
     
     
         23 . A cell comprising the nucleic acid of  claim 20  or a vector comprising the nucleic acid. 
     
     
         24 . A composition comprising (i) the nucleic acid of  claim 20  a vector comprising the nucleic acid, or a cell comprising the nucleic acid or vector, and (ii) a carrier. 
     
     
         25 . A construct comprising
 two fusion proteins of A-(optional linker)-C(Formula (III)), and   two fusion proteins of B-(optional linker)-D-(optional linker)-E (Formula (IV)),   wherein A is an antibody or antibody fragment, B is the polypeptide of  claim 1 , C is an immunoglobulin light chain constant region, D is an immunoglobulin heavy chain constant region, and E is an Fc region or portion thereof.   
     
     
         26 . The construct of  claim 25 , wherein the fusion protein of Formula (III) comprises SEQ ID NO: 19 and the fusion protein of Formula (IV) comprises SEQ ID NO: 18. 
     
     
         27 . A construct comprising
 two fusion proteins of A-(optional linker)-C(Formula (III)), and   two fusion proteins of B-(optional linker)-D-(optional linker)-E-(optional linker)-B (Formula (II)),   wherein A is an antibody or antibody fragment, B is the polypeptide of  claim 1 , C is an immunoglobulin light chain constant region, D is an immunoglobulin heavy chain constant region, and E is an Fc region or portion thereof.   
     
     
         28 . The construct of  claim 27 , wherein the fusion protein of Formula (III) comprises SEQ ID NO: 21 and the fusion protein of Formula (II) comprises SEQ ID NO: 20. 
     
     
         29 . A construct comprising
 two fusion proteins of A-(optional linker)-C-(optional linker)-B (Formula (I)), and   two fusion proteins of B-(optional linker)-D-(optional linker)-E-(optional linker)-B (Formula (II)),   wherein A is an antibody or antibody fragment, B is the polypeptide of  claim 1 , C is an immunoglobulin light chain constant region, D is an immunoglobulin heavy chain constant region, and E is an Fc region or portion thereof.   
     
     
         30 . The construct of  claim 29 , wherein the fusion protein of Formula (I) comprises SEQ ID NO: 23 and the fusion protein of Formula (II) comprises SEQ ID NO: 22. 
     
     
         31 . (canceled) 
     
     
         32 . A composition comprising the construct of  claim 25  and a carrier. 
     
     
         33 . A conjugate comprising (a) the polypeptide of  claim 1  and (b) a cytotoxic agent. 
     
     
         34 . The conjugate of  claim 33 , wherein the cytotoxic agent is a toxin. 
     
     
         35 . A composition comprising the conjugate of  claim 33  and a carrier. 
     
     
         36 . A method of prophylactically or therapeutically inhibiting a viral infection in a cell or host comprising administering to the cell or host (i) the polypeptide of  claim 1 , a vector comprising the nucleic acid, or a cell comprising the nucleic acid or vector, or (ii) a composition thereof, such that the viral infection is inhibited. 
     
     
         37 . The method of  claim 36 , wherein the viral infection is an HIV infection. 
     
     
         38 . The method of  claim 37 , wherein the HIV infection is an HIV-1 infection. 
     
     
         39 . A method of eradicating viral-infected cells in a subject comprising administering the conjugate of  claim 33  or a composition thereof to the subject, thereby eradicating the viral-infected cells in the subject. 
     
     
         40 . The method of  claim 39 , wherein the viral-infected cells are HIV-infected cells. 
     
     
         41 . The method of  claim 40 , wherein the HIV-infected cells are HIV-1 infected cells.

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