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Polypeptides For Generating Anti Influenza Antibodies And Uses Thereof

Abstract: The present disclosure relates to a polypeptide comprising hemagglutinin stem domain fragments that can elicit broadly cross-reactive anti-influenza antibodies and confer protection against influenza virus. The disclosure also provides a method of preparing the polypeptide with biochemical and biophysical properties that enhance its immunogenic properties. Also provided are recombinant DNA constructs, vectors, and host cells comprising the nucleic acid encoding the polypeptide, as well as uses of the polypeptide, particularly in the prevention, and detection of influenza.

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Notices, Deadlines & Correspondence

Patent Information

Application #
Filing Date
01 May 2014
Publication Number
01/2016
Publication Type
INA
Invention Field
BIOTECHNOLOGY
Status
Email
lsmds@lakshmisri.com
Parent Application
Patent Number
Legal Status
Grant Date
2022-01-25
Renewal Date

Applicants

INDIAN INSTITUTE OF SCIENCE
Indian Institute of Science, Bangalore - 560012

Inventors

1. VARADARAJAN, Raghavan
Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560012
2. MALLAJOSYULA, Vamsee V Aditya
Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560012

Specification

CLIAMS:1. A polypeptide comprising a first subunit, a second subunit, and a third subunit, wherein the amino acid sequence of the first subunit shares atleast 70%-100% sequence similarity to an amino acid sequence as set forth in SEQ ID NO: 1, wherein the amino acid sequence of the second subunit shares atleast 70%-100% sequence similarity to an amino acid sequence as set forth in SEQ ID NO: 2, wherein the amino acid sequence of the third subunit shares atleast 70%-100% sequence similarity to an amino acid sequence as set forth in SEQ ID NO: 3, and wherein each subunit is connected by a linker.
2. The polypeptide as claimed in claim 1, wherein each of the first, second, and third subunit is further modified.
3. The polypeptide as claimed in claim 1, wherein the second subunit having amino acid sequence atleast 70% similar to a sequence as set forth in SEQ ID NO: 2 is modified at amino acid residues selected from the group consisting of I9, V12, I14, and C17, and wherein the third subunit having amino acid sequence atleast 70% similar to a sequence as set forth in SEQ ID NO: 3 is modified at amino acid residues selected from the group consisting of V26, F70, F23, L33, S14, and N42.
4. The polypeptide as claimed in claim 1, wherein the nucleotide sequence encoding the first subunit shares atleast 70%-100% sequence similarity to a polynucleotide sequence as set forth in SEQ ID NO: 4, wherein the nucleotide sequence encoding the second subunit shares atleast 70%-100% sequence similarity to a polynucleotide sequence as set forth in SEQ ID NO: 5, and wherein the nucleotide sequence encoding the third subunit shares atleast 70%-100% sequence similarity to a polynucleotide sequence as set forth in SEQ ID NO: 6.
5. The polypeptide as claimed in claim 1, wherein the amino acid sequence of the first subunit is selected from the group consisting of SEQ ID NO: 7, SEQ ID NO: 8, and SEQ ID NO: 9, wherein the amino acid sequence of the second subunit is selected from the group consisting of SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, and SEQ ID NO: 13, and wherein the amino acid sequence of the third subunit is selected from the group consisting of SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, and SEQ ID NO: 17.
6. The polypeptide as claimed in claim 5, wherein the nucleotide sequence encoding the first subunit is selected from the group consisting of SEQ ID NO: 18, SEQ ID NO: 19, and SEQ ID NO: 20, wherein the nucleotide sequence encoding the second subunit is selected from the group consisting of SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, and SEQ ID NO: 24, and wherein the nucleotide sequence encoding the third subunit is selected from the group consisting of SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, and SEQ ID NO: 28.
7. The polypeptide as claimed in claim 1, wherein the linkers of variable length have amino acid sequence selected from the group consisting of GSA, SEQ ID NO: 47, and SEQ ID NO: 30.
8. The polynucleotide as claimed in claim 7, wherein the nucleotide sequence encoding the linkers is selected from the group consisting of GGCAGCGCG, SEQ ID NO: 48, and SEQ ID NO: 29.
9. The polynucleotide as claimed in claim 1, further comprising a C-terminal trimerization motif.
10. The polynucleotide as claimed in claim 9, wherein the C-terminal trimerization motif amino acid sequence selected from the group consisting of SEQ ID NO: 31, and SEQ ID NO: 32.
11. The polynucleotide as claimed in claim 10, wherein the nucleotide sequence encoding the C-terminal trimerization motif is selected from the group consisting of SEQ ID NO: 33, and SEQ ID NO: 34.
12. The polypeptide as claimed in claim 1, wherein the amino acid sequence of the polypeptide is selected from the group consisting of SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39 and SEQ ID NO: 40.
13. The polypeptide as claimed in claim 12, wherein the nucleotide sequence encoding the polypeptide is selected from the group consisting of SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45 and SEQ ID NO: 46.
14. A recombinant DNA construct comprising a polynucleotide fragment operably linked to a promoter, wherein said polynucleotide fragment encodes a polypeptide as claimed in claim 1.
15. A recombinant vector comprising a recombinant DNA construct as claimed in claim 14.
16. A recombinant host cell comprising a recombinant vector as claimed in claim 15, wherein the recombinant host cell is selected from the group consisting of a bacterial cell, fungal cell, and mammalian cell, preferably E.coli.
17. An influenza vaccine comprising a polypeptide as claimed in any of the claims 1-13.
18. A method to produce a vaccine against influenza, said method comprising:
a. obtaining a polypeptide as claimed in any of the claims 1-13;
b. expressing the polypeptide from(a)in a host cell as claimed in claim 16; and
c. purifying the expressed polypeptide from (b).
19. An influenza vaccine comprising a polynucleotide fragment encoding a polypeptide as claimed in claim 1.
,TagSPECI:As Attached

Documents

Application Documents

# Name Date
1 SQ.txt 2014-05-02
2 SPEC FOR FILING.pdf 2014-05-02
3 FORM 5.pdf 2014-05-02
4 FORM 3.pdf 2014-05-02
5 FIGURES FOR FILING.pdf 2014-05-02
6 2208-CHE-2014 POWER OF ATTORNEY 04-06-2014.pdf 2014-06-04
7 2208-CHE-2014 CORRESPONDENCE OTHERS 04-06-2014.pdf 2014-06-04
8 2208-CHE-2014 FORM-1 29-10-2014.pdf 2014-10-29
9 2208-CHE-2014 CORRESPONDENCE OTHERS 29-10-2014.pdf 2014-10-29
10 PD012942PCT_Request for Priority Documents-PCT.pdf 2015-06-01
11 Form 3 [10-03-2017(online)].pdf 2017-03-10
12 2208-CHE-2014-FORM 18 [20-03-2018(online)].pdf 2018-03-20
13 2208-CHE-2014-FER.pdf 2020-06-11
14 2208-CHE-2014-Information under section 8(2) [08-12-2020(online)].pdf 2020-12-08
15 2208-CHE-2014-FORM 3 [08-12-2020(online)].pdf 2020-12-08
16 2208-CHE-2014-FER_SER_REPLY [08-12-2020(online)].pdf 2020-12-08
17 2208-CHE-2014-CLAIMS [08-12-2020(online)].pdf 2020-12-08
18 2208-CHE-2014-Annexure [08-12-2020(online)].pdf 2020-12-08
19 2208-CHE-2014-EDUCATIONAL INSTITUTION(S) [12-11-2021(online)].pdf 2021-11-12
20 2208-CHE-2014-US(14)-HearingNotice-(HearingDate-06-01-2022).pdf 2021-11-23
21 2208-CHE-2014-Correspondence to notify the Controller [26-11-2021(online)].pdf 2021-11-26
22 2208-CHE-2014-FORM-26 [05-01-2022(online)].pdf 2022-01-05
23 2208-CHE-2014-Written submissions and relevant documents [20-01-2022(online)].pdf 2022-01-20
24 2208-CHE-2014-PatentCertificate25-01-2022.pdf 2022-01-25
25 2208-CHE-2014-IntimationOfGrant25-01-2022.pdf 2022-01-25
26 387309.Form 27.pdf 2023-11-20

Search Strategy

1 SearchStrategy2208CHE2014E_05-06-2020.pdf

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