Methods and compositions for treating and preventing hiv

Patent metadata

Field	Value
Publication number	US-2020101152-A1
Application number	US-201916708787-A
Country	US
Kind code	A1
Filing date	Dec 10, 2019
Priority date	Sep 26, 2017
Publication date	Apr 2, 2020
Grant date	—

Abstract

Methods and compositions are provided that can be used to vaccinate against and treat HIV. Specifically contemplated are vaccine compositions and methods of using these compositions treat HIV in patients. Aspects of the disclosure relate to an anti-CD40 antibody-HIV antigen fusion protein comprising (i) an anti-CD40 heavy chain (HCD40)-HIV antigen (Ag) fusion protein comprising the formula: HCD40-Ag, wherein Ag is a polypeptide with at least 80% sequence identity to SEQ ID NO:1; and (ii) an anti-CD40 light chain (LCD40).

First claim

What is claimed is:

1 . A polynucleotide encoding a fusion protein, wherein said fusion protein is an anti-Dendritic Cell (DC) receptor antibody-HIV antigen fusion protein comprising,
(i) an anti-DC receptor heavy chain (HDCR)-HIV antigen (Ag) fusion protein comprising the formula: HDCR-Ag, wherein Ag is a polypeptide with at least 80% sequence identity to SEQ ID NO:1; and (ii) an anti-DC receptor light chain (LDCR).

2 . The polynucleotide of claim 1 , wherein the fusion protein further comprises one or more peptide linkers (PL).

3 . The fusion protein of claim 1 , wherein the fusion protein comprises:
(i) HDCR-PL-Ag; and (ii) LDCR.

4 . The polynucleotide of claim 1 , wherein the fusion protein further comprises one or more joining sites (JS), wherein the joining site comprises alanine and serine residues.

5 . The polynucleotide of claim 1 , wherein the fusion protein further comprises one or more joining sites (JS), wherein the joining site consists of alanine and serine residues.

6 . The polynucleotide of claim 1 , wherein the fusion protein comprises:
(i) HDCR-JS-PL-JS-Ag-JS; and (ii) LCD40; wherein JS is a joining site and PL is a peptide linker, and LCD40 is an anti-CD40 light chain.

7 . The polynucleotide of claim 2 , wherein the peptide linker comprises a polypeptide with at least 80% sequence identity to SEQ ID NO:2.

8 . The polynucleotide of claim 3 , wherein PL-Ag comprises a polypeptide with at least 80% identity to SEQ ID NO:3.

9 . The polynucleotide of claim 3 , wherein the fusion protein is an anti-CD40 antibody-HIV antigen fusion protein comprising
(i) an anti-CD40 heavy chain (HCD40)-HIV antigen (Ag) fusion protein comprising the formula: HCD40-Ag, wherein Ag is a polypeptide with at least 80% sequence identity to SEQ ID NO:1; and (ii) an anti-CD40 light chain (LCD40).

10 . The polynucleotide of claim 9 , wherein the anti-CD40 antibody is a human or humanized anti-CD40 antibody.

11 . The polynucleotide of claim 9 , wherein the anti-CD40 antibody comprises human IgG4 heavy chain constant region.

12 . The polynucleotide of claim 11 , wherein the human IgG4 heavy chain constant region comprises one or both of S241P and L248E substitutions.

13 . The polynucleotide of claim 9 , wherein the HCD40 comprises a polypeptide with at least 80% sequence identity to SEQ ID NO:4.

14 . The polynucleotide of claim 9 , wherein the LCD40 comprises a polypeptide with at least 80% sequence identity to SEQ ID NO:5.

15 . The polynucleotide of claim 9 , wherein HCDR comprises the complementarity determining regions CDR1H, CDR2H and CDR3H, the CDR1H having the amino acid sequence GFTFSDYYMY (SEQ ID NO:10), the CDR2H having the amino acid sequence YINSGGGSTYYPDTVKG (SEQ ID NO.:11), and the CDR3H having the amino acid sequence RGLPFHAMDY (SEQ ID NO.:12).

16 . The polynucleotide of claim 9 , wherein LCD40 comprises the complementarity determining regions CDR1L, CDR2L and CDR3L, the CDR1L having the amino acid sequence SASQGISNYLN (SEQ ID NO.:13) the CDR2L having the amino acid sequence YTSILHS (SEQ ID NO.:14) and the CDR3L having the amino acid sequence QQFNKLPPT (SEQ ID NO.:15).

17 . The polynucleotide of claim 9 , comprising
(i) a HCD40-Ag fusion protein comprising an amino acid sequence with at least 80% sequence identity to SEQ ID NO:6; and (ii) a LCD40 comprising an amino acid sequence with at least 80% identity to SEQ ID NO:5.

18 . The polynucleotide of claim 9 , wherein HCDR comprises the complementarity determining regions CDR1H, CDR2H and CDR3H, the CDR1H having the amino acid sequence GYSFTGYYMH (SEQ ID NO.:18), the CDR2H having the amino acid sequence RINPYNGATSYNQNFKD (SEQ ID NO.:19), and the CDR3H having the amino acid sequence EDYVY (SEQ ID NO.:20).

19 . The polynucleotide of claim 9 , wherein LCD40 comprises the complementarity determining regions CDR1L, CDR2L and CDR3L, the CDR1L having the amino acid sequence RSSQSLVHSNGNTYLH (SEQ ID NO.:21) the CDR2L having the amino acid sequence KVSNRFS (SEQ ID NO.:22) and the CDR3L having the amino acid sequence SQSTHVPWT (SEQ ID NO.:23).

20 . The polynucleotide of claim 9 , wherein HCDR comprises the complementarity determining regions CDR1H, CDR2H and CDR3H, the CDR1H having the amino acid sequence GYTFTDYVLH (SEQ ID NO.:26), the CDR2H having the amino acid sequence YINPYNDGTKYNEKFKG (SEQ ID NO.:27), and the CDR3H having the amino acid sequence GYPAYSGYAMDY (SEQ ID NO.:28).

21 . The polynucleotide of claim 9 , wherein LCD40 comprises the complementarity determining regions CDR1L, CDR2L and CDR3L, the CDR1L having the amino acid sequence RASQDISNYLN (SEQ ID NO.:29) the CDR2L having the amino acid sequence YTSRLHS (SEQ ID NO.:30) and the CDR3L having the amino acid sequence HHGNTLPWT (SEQ ID NO.:31)

22 . A polynucleotide comprising a nucleotide sequence that is at least 80% identical to SEQ ID NO: 7.

23 . A polynucleotide comprising a nucleotide sequence that is at least 80% identical to SEQ ID NO: 8.

24 . An expression vector comprising the polynucleotides of claim 22 , and wherein the the expression vector further comprises a polynucleotide comprising a nucleotide sequence that is at least 80% identical to SEQ ID NO: 8.

25 . An expression vector comprising the polynucleotide of claim 1 .

26 . A host cell comprising the polynucleotide of claim 1 .

27 . The host cell of claim 26 , wherein the host cell is a mammalian cell.

28 . The host cell of claim 27 , wherein the mammalian cell is a CHO cell.

29 . A fusion protein produced from the host cell of claim 26 .

Assignees

• Inst Nat Sante Rech Med
• Baylor Res Institute
• Univ Paris Val De Marne
• Hopitaux Paris Assist Publique

Inventors

• Levy Yves
• Zurawski Gerard
• Zurawski Sandra
• Flamar Anne-Laure

Classifications

• C12N2740/16034

  Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein · CPC title

• C07K16/28

  against receptors, cell surface antigens or cell surface determinants · CPC title

• A61K39/12

  Viral antigens · CPC title

• C07K2317/34

  Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues · CPC title

• C07K2317/76

  Antagonist effect on antigen, e.g. neutralization or inhibition of binding · CPC title