US 8,524,868 B2Granted

Polypeptide fragments of the hepatitis E virus, the vaccine composition comprising said fragments and the diagnostic kits

AssigneesBeijing Wantai Biological Pharmacy Enterprise Co., Ltd., Xiamen University

InventorsNingshao Xia, Jun Zhang, Shaowei Li, Shengxiang Ge, Ying Gu, Zhiqiang He

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Abstract

The present invention relates to polypeptide(s) comprising the amino acid sequence as set forth in SEQ ID No. 1 of hepatitis E virus ORF 2 or its fragment, which is in the form of n-polymeric polypeptide, wherein n is an integer from 1-180; to a chimeric protein consisting of a polypeptide of the present invention and a conserved fragment of hemagglutin antigen from influenza virus; to a polypeptide of the present invention bound to a polypeptide containing epitope from hepatitis E virus ORF3 or an immunogenic fragment thereof; to a recombinant expression vector comprising the DNA molecule encoding the above polypeptides and the host cell transformed with said recombinant expression vector which is able to express polypeptide of the present invention. The present invention further relates to a vaccine composition against hepatitis E virus which comprises the above-mentioned polypeptide, or diagnostic kit for hepatitis E virus infection comprising the above-mentioned polypeptide, which includes IgG, IgM, or total antibody diagnostic kit for hepatitis E virus, and to the use of vaccine composition and diagnostic kit for prophylaxis, diagnosis and/or treatment of hepatitis E virus infection.

Claims26

Dependent claims

A multimer of purified monomeric polypeptides, wherein said multimer is formed by 2-180 purified monomeric polypeptides via self-aggregation, and each said purified monomeric polypeptide is selected from the group consisting of

(a) a fragment of SEQ ID No. 1 of hepatitis E virus ORF 2 wherein the amino terminus starts from between amino acid residues 370 and 469, and the carboxyl terminus ends from between amino add residues 601 and 628, wherein the fragment of SEQ ID No. 1 is selected from the group consisting of
a polypeptide having the amino acid sequence of amino acid residues 394 to 628 from SEQ ID No. 1,
a polypeptide having the amino acid sequence of amino acid residues 394 to 618 from SEQ ID No. 1,
a polypeptide having the amino acid sequence of amino acid residues 394 to 602 from SEQ ID No. 1,
a polypeptide having the amino acid sequence of amino acid residues 394 to 601 from SEQ ID No. 1,
a polypeptide having the amino acid sequence of amino acid residues 394 to 606 from SEQ ID No. 1,
a polypeptide having the amino acid sequence of amino acid residues 390 to 603 from SEQ ID No. 1,
a polypeptide having the amino acid sequence of amino acid residues 374 to 618 from SEQ ID No. 1,
a polypeptide having the amino acid sequence of amino acid residues 414 to 602 from SEQ ID No. 1,
a polypeptide having the amino acid sequence of amino acid residues 414 to 601 from SEQ ID No. 1, and
a polypeptide having the amino acid sequence of amino acid residues 459 to 628 from SEQ ID No. 1, and
(b) a polypeptide having the amino acid sequence of amino acid residues X to 603 from SEQ ID No. 1 with Met added at the N-terminus and a modified C-terminus, wherein the modified C-terminus is an addition, in the 5′ to 3′ direction, of amino acid sequence -Pro-Pro-Arg at amino acid residue 603, Pro, on its 3′ end and wherein
when X is amino acid residue 394, the polypeptide is as set forth in SEQ ID No. 2;
when X is amino acid residue 414, the polypeptide is as set forth in SEQ ID No. 3;
when X is amino acid residue 429, the polypeptide is as set forth in SEQ ID No. 4;
when X is amino acid residue 439, the polypeptide is as set forth in SEQ ID No. 7;
when X is amino acid residue 449, the polypeptide is as set forth in SEQ ID No. 8;
when X is amino acid residue 459, the polypeptide is as set forth in SEQ ID No. 9;
or
when X is amino acid residue 469, the polypeptide is as set forth in SEQ ID No. 10.

17 more elements

A chimeric protein comprising a polypeptide selected from the group consisting of

a polypeptide having the amino acid sequence of amino acid residues 394 to 628 from SEQ ID No. 1,
a polypeptide having the amino acid sequence of amino acid residues 394 to 618 from SEQ ID No. 1,
a polypeptide having the amino acid sequence of amino acid residues 394 to 602 from SEQ ID No. 1,
a polypeptide having the amino acid sequence of amino acid residues 394 to 601 from SEQ ID No. 1,
a polypeptide having the amino acid sequence of amino acid residues 394 to 606 from SEQ ID No. 1,
a polypeptide having the amino acid sequence of amino acid residues 390 to 603 from SEQ ID No. 1,
a polypeptide having the amino acid sequence of amino acid residues 374 to 618 from SEQ ID No. 1,
a polypeptide having the amino acid sequence of amino acid residues 414 to 602 from SEQ ID No. 1,
a polypeptide having the amino acid sequence of amino acid residues 414 to 601 from SEQ ID No. 1,
a polypeptide having the amino acid sequence of amino acid residues 459 to 628 from SEQ ID No.1, and
a polypeptide having the amino acid sequence of amino acid residues X to 603 from SEQ ID No. 1 with Met added at the N-terminus and a modified C-terminus, wherein the modified C-terminus is an addition, in the 5′ to 3′ direction, of amino acid sequence -Pro-Pro-Arg at amino acid residue 603, Pro, on its 3′ end and wherein
when X is amino acid residue 394, the polypeptide is as set forth in SEQ ID No. 2;
when X is amino acid residue 414, the polypeptide is as set forth in SEQ ID No. 3;
when X is amino acid residue 429, the polypeptide is as set forth in SEQ ID No. 4;
when X is amino acid residue 439, the polypeptide is as set forth in SEQ ID No. 7;
when X is amino acid residue 449, the polypeptide is as set forth in SEQ ID No. 8;
when X is amino acid residue 459, the polypeptide is as set forth in SEQ ID No. 9;
or
when X is amino acid residue 469, the polypeptide is as set forth in SEQ ID No. 10;
and a conserved fragment of hemagglutinin antigen from influenza virus.

17 more elements

A chimeric protein comprising a polypeptide selected from the group consisting of

a polypeptide having the amino acid sequence of amino acid residues 394 to 628 from SEQ ID No. 1,
a polypeptide having the amino acid sequence of amino acid residues 394 to 618 from SEQ ID No. 1,
a polypeptide having the amino acid sequence of amino acid residues 394 to 602 from SEQ ID No. 1,
a polypeptide having the amino acid sequence of amino acid residues 394 to 601 from SEQ ID No. 1,
a polypeptide having the amino acid sequence of amino acid residues 394 to 606 from SEQ ID No. 1,
a polypeptide having the amino acid sequence of amino acid residues 390 to 603 from SEQ ID No. 1,
a polypeptide having the amino acid sequence of amino acid residues 374 to 618 from SEQ ID No. 1,
a polypeptide haying the amino acid sequence of amino acid residues 414 to 602 from SEQ ID No. 1,
a polypeptide having the amino acid sequence of amino acid residues 414 to 601 from SEQ ID No. 1,
a polypeptide having the amino acid sequence of amino acid residues 459 to 628 from SEQ ID No. 1, and
a polypeptide having the amino acid sequence of amino acid residues X to 603 from SEQ ID No. 1 with Met added at the N-terminus and a modified C-terminus, wherein the modified C-terminus is an addition, in the 5′ to 3′ direction, of amino acid sequence -Pro-Pro-Arg at amino acid residue 603, Pro, on its 3′ end and wherein
when X is amino acid residue 394, the polypeptide is as set forth in SEQ ID No. 2;
when X is amino acid residue 414, the polypeptide is as set forth in SEQ ID No. 3;
when X is amino acid residue 429, the polypeptide is as set forth in SEQ ID No. 4;
when X is amino acid residue 439, the polypeptide is as set forth in SEQ ID No. 7;
when X is amino acid residue 449, the polypeptide is as set forth in SEQ ID No. 8;
when X is amino acid residue 459, the polypeptide is as set forth in SEQ ID No. 9;
or when X is amino acid residue 469, the polypeptide is as set forth in SEQ ID No. 10;
and an immunogenic epitope from hepatitis E virus ORF3 or an immunogenic fragment thereof.

16 more elements

A recombinant expression vector comprising the nucleotide sequence encoding a polypeptide selected from the group consisting of

a polypeptide having the amino acid sequence of amino acid residues 394 to 628 from SEQ ID No. 1,
a polypeptide having the amino acid sequence of amino acid residues 394 to 618 from SEQ ID No. 1,
a polypeptide having the amino acid sequence of amino acid residues 394 to 602 from SEQ ID No. 1,
a polypeptide having the amino acid sequence of amino acid residues 394 to 601 from SEQ ID No. 1,
a polypeptide having the amino acid sequence of amino acid residues 394 to 606 from SEQ ID No. 1,
a polypeptide having the amino acid sequence of amino acid residues 390 to 603 from SEQ ID No. 1,
a polypeptide having the amino acid sequence of amino acid residues 374 to 618 from SEQ ID No. 1,
a polypeptide having the amino acid sequence of amino acid residues 414 to 602 from SEQ ID No. 1,
a polypeptide having the amino acid sequence of amino acid residues 414 to 601 from SEQ ID No. 1,
a polypeptide having the amino acid sequence of amino acid residues 459 to 628 from SEQ ID No.1, and
a polypeptide having the amino acid sequence of amino acid residues X to 603 from SEQ ID No. 1 with Met added at the N-terminus and a modified C-terminus, wherein the modified C-terminus is an addition, in the 5′ to 3′ direction, of amino acid sequence -Pro-Pro-Arg at amino acid residue 603, Pro, on its 3′ end and wherein
when X is amino acid residue 394, the polypeptide is as set forth in SEQ ID No. 2;
when X is amino acid residue 414, the polypeptide is as set forth in SEQ ID No. 3;
when X is amino acid residue 429, the polypeptide is as set forth in SEQ ID No. 4;
when X is amino acid residue 439, the polypeptide is as set forth in SEQ ID No. 7;
when X is amino acid residue 449, the polypeptide is as set forth in SEQ ID No. 8;
when X is amino acid residue 459, the polypeptide is as set forth in SEQ ID No. 9;
or
when X is amino acid residue 469, the polypeptide is as set forth in SEQ ID No. 10.

16 more elements

A vaccine composition for prophylaxis of hepatitis E virus infection in mammals, which comprises a polypeptide selected from the group consisting of

a polypeptide having the amino acid sequence of amino acid residues 394 to 628 from SEQ ID No. 1,
a polypeptide having the amino acid sequence of amino acid residues 394 to 618 from SEQ ID No. 1,
a polypeptide having the amino acid sequence of amino acid residues 394 to 602 from SEQ ID No. 1,
a polypeptide having the amino acid sequence of amino acid residues 394 to 601 from SEQ ID No. 1,
a polypeptide having the amino acid sequence of amino acid residues 394 to 606 from SEQ ID No. 1,
a polypeptide having the amino acid sequence of amino acid residues 390 to 603 from SEQ ID No. 1,
a polypeptide having the amino acid sequence of amino acid residues 374 to 618 from SEQ ID No. 1,
a polypeptide having the amino acid sequence of amino acid residues 414 to 602 from SEQ ID No. 1,
a polypeptide having the amino acid sequence of amino acid residues 414 to 601 from SEQ ID No. 1,
a polypeptide having the amino acid sequence of amino acid residues 459 to 628 from SEQ ID No. 1, and
a polypeptide having the amino acid sequence of amino acid residues X to 603 from SEQ ID No. 1 with Met added at the N-terminus and a modified C-terminus, wherein the modified C-terminus is an addition, in the 5′ to 3′ direction, of amino acid sequence -Pro-Pro-Arg at amino acid residue 603, Pro, on its 3′ end and wherein
when X is amino acid residue 394, the polypeptide is as set forth in SEQ ID No. 2;
when X is amino acid residue 414, the polypeptide is as set forth in SEQ ID No. 3;
when X is amino acid residue 429, the polypeptide is as set forth in SEQ ID No. 4;
when X is amino acid residue 439, the polypeptide is as set forth in SEQ ID No. 7;
when X is amino acid residue 449, the polypeptide is as set forth in SEQ ID No. 8;
when X is amino acid residue 459, the polypeptide is as set forth in SEQ ID No. 9;
or
when X is amino acid residue 469, the polypeptide is as set forth in SEQ ID No. 10;
and
optionally, pharmaceutically acceptable vehicles and/or an adjuvant.

18 more elements

A diagnostic kit for the diagnosis of hepatitis E virus infection in biological sample, which comprises a diagnosis effective amount of a polypeptide selected from the group consisting of

a polypeptide having the amino acid sequence of amino acid residues 394 to 628 from SEQ ID No. 1,
a polypeptide having the amino acid sequence of amino acid residues 394to 618 from SEQ ID No. 1,
a polypeptide having the amino acid sequence of amino acid residues 394 to 602 from SEQ ID No. 1,
a polypeptide having the amino acid sequence of amino acid residues 394 to 601 from SEQ ID No. 1,
a polypeptide having the amino acid sequence of amino acid residues 394 to 606 from SEQ ID No. 1,
a polypeptide having the amino acid sequence of amino acid residues 390 to 603 from SEQ ID No. 1,
a polypeptide having the amino acid sequence of amino acid residues 374 to 618 from SEQ ID No. 1,
a polypeptide having the amino acid sequence of amino acid residues 414 to 602 from SEQ ID No. 1,
a polypeptide having the amino acid sequence of amino acid residues 414 to 601 from SEQ ID No. 1,
a polypeptide having the amino acid sequence of amino acid residues 459 to 628 from SEQ ID No.1, and
a polypeptide having the amino acid sequence of amino acid residues X to 603 from SEQ ID No. 1 with Met added at the N-terminus and a modified C-terminus, wherein the modified C-terminus is an addition, in the 5′ to 3′ direction, of amino acid sequence -Pro-Pro-Arg at amino acid residue 603, Pro, on its 3′ end and wherein
when X is amino acid residue 394, the polypeptide is as set forth in SEQ ID No. 2;
when X is amino acid residue 414, the polypeptide is as set forth in SEQ ID No. 3;
when X is amino acid residue 429, the polypeptide is as set forth in SEQ ID No. 4;
when X is amino acid residue 439, the polypeptide is as set forth in SEQ ID No. 7;
when X is amino acid residue 449, the polypeptide is as set forth in SEQ ID No. 8;
when X is amino acid residue 459, the polypeptide is as set forth in SEQ ID No. 9;
or
when X is amino acid residue 469, the polypeptide is as set forth in SEQ ID No. 10.

16 more elements

Dependencies are inferred from the claim text.

Facts

Application: 12/614,896Filed 9 Nov 2009 · continuation
Priority: CN 00 1 3063430 Sep 2000
Published: US 2010/0143410 A117 Jun 2010
Granted: 3 Sep 2013
Term ends: Not estimatedThe source records don’t support an estimate.

Classification23 codes

C07K 14/005
Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof: from viruses
A61K 39/12
Medicinal preparations containing antigens or antibodies: viral antigens
A61K 39/29
Viral antigens: hepatitis virus
A61P 1/16
Drugs for disorders of the alimentary tract or the digestive system: for liver or gallbladder disorders, e.g. hepatoprotective agents,…

Family

PCT/CN01/01469Parent of this division · filed 30 Sep 2001
Application12/557,741Parent of this continuation · filed 11 Sep 2009
US 2010/0150962 A1Pre-grant publication · published 17 Jun 2010
Application10/381,770Parent of this division
US 7,615,228 B2Parent of this division
Application12/557,741Parent of this division
US 2004/0052813 A1Published application
US 2010/0143410 A1Published application
US 8,715,695 B2Related patent
US 8,524,868 B2This patent

From the US filing history. Foreign family members aren’t listed.