Abstract: The present invention relates to plasmids encoding insulin antigens and cytokines for use in tolerizing immunization in particular for the prevention and/or delay of e.g. type 1 diabetes.
1. A plasmid which encodes:
i. an insulin antigen; ii. TGF-3; and iii. IL-10.
2. The plasmid according to claim 1, wherein said insulin antigen is selected from the group consisting of: proinsulin, pre-proinsulin, and a functional or immuno-dominant peptide fragment thereof.
3. The plasmid according to any one of the preceding claims, wherein said insulin antigen is endosomally targeted insulin.
4. The plasmid according to any one of the preceding claims, wherein said plasmid expresses insulin antigen and TGF-3 in an amount of at least 2 fold lower than IL-10.
5. The plasmid according to any one of the preceding claims, wherein said plasmid furthermore co-expresses lnterleukin-2 (IL-2).
6. The plasmid according to any one of the preceding claims, wherein said plasmid comprises: (i) an FMDV 2A element separating the insulin antigen encoding sequence and the TGF-3 encoding sequence, (ii) an EMCV IRES element separating the TGF-3 encoding sequence and the IL-10 encoding sequence, and (iii) a 2A element separating the IL-10 encoding sequence and the IL-2 encoding sequence.
7. The plasmid according to any one of the preceding claims, wherein the TGF-3 encoding sequence encodes constitutively active TGF-3-
8. The plasmid according to any one of the preceding claims, wherein said plasmid comprises: (i) an endosomally targeted pre-pro-insulin encoding sequence, (ii) an FMDV 2A element, (iii) a TGF-3 encoding sequence, (iv) an EMCV IRES element, (v) an IL-10 encoding sequence, (vi) a P 2A element, (vii) an IL-2 encoding sequence, (viii) a polyadenylation / termination element, (ix) a selection gene, (x) an origin of
replication, (xi) a eukaryotic promoter element, (xii) a eukaryotic translational start sequence, (xiii) an endosomal sorting sequence, and (xiv) optionally an intron.
9. A DNA immuno-therapy vaccine comprising a plasmid according to any one of the preceding claims.
10. The DNA immuno-therapy vaccine according to claim 9, or a plasmid according to any one of claims 1-8, for use in delaying or preventing type I diabetes.
11. The DNA immuno-therapy vaccine according to claim 9, or a plasmid according to any one of claims 1-8, for subcutaneous administration.
12. The DNA immuno-therapy vaccine according to claim 9, or a plasmid according to any one of claims 1-8, for intra-muscular administration.
13. A pharmaceutical composition comprising the DNA immuno-therapy vaccine according to claim 9, or a plasmid according to any one of claims 1-8, wherein said pharmaceutical composition comprises a saline solution and/or a buffer and/or a chelator.
14. The pharmaceutical composition according to claim 13, wherein said buffer does not comprise any virus, lipid co-packing agent, or condensation agent.
15. The pharmaceutical composition according to any one of claims 13-14, wherein said composition furthermore comprises a GLP-1R agonist.
| # | Name | Date |
|---|---|---|
| 1 | 201947019298.pdf | 2019-05-15 |
| 2 | 201947019298-STATEMENT OF UNDERTAKING (FORM 3) [15-05-2019(online)].pdf | 2019-05-15 |
| 3 | 201947019298-SEQUENCE LISTING(PDF) [15-05-2019(online)].pdf | 2019-05-15 |
| 4 | 201947019298-SEQUENCE LISTING [15-05-2019(online)].txt | 2019-05-15 |
| 5 | 201947019298-PRIORITY DOCUMENTS [15-05-2019(online)].pdf | 2019-05-15 |
| 6 | 201947019298-POWER OF AUTHORITY [15-05-2019(online)].pdf | 2019-05-15 |
| 7 | 201947019298-FORM 18 [15-05-2019(online)].pdf | 2019-05-15 |
| 8 | 201947019298-FORM 1 [15-05-2019(online)].pdf | 2019-05-15 |
| 9 | 201947019298-FIGURE OF ABSTRACT [15-05-2019(online)].jpg | 2019-05-15 |
| 10 | 201947019298-DRAWINGS [15-05-2019(online)].pdf | 2019-05-15 |
| 11 | 201947019298-DECLARATION OF INVENTORSHIP (FORM 5) [15-05-2019(online)].pdf | 2019-05-15 |
| 12 | 201947019298-COMPLETE SPECIFICATION [15-05-2019(online)].pdf | 2019-05-15 |
| 13 | Correspondence by Agent_Form-5, POA, PCT AND SEQUENCE LISTING(CD)_20-05-2019.pdf | 2019-05-20 |
| 14 | 201947019298-Proof of Right (MANDATORY) [06-11-2019(online)].pdf | 2019-11-06 |
| 15 | 201947019298-FORM 3 [06-11-2019(online)].pdf | 2019-11-06 |
| 16 | 201947019298-FORM-26 [18-12-2019(online)].pdf | 2019-12-18 |
| 17 | 201947019298-FORM 3 [27-04-2020(online)].pdf | 2020-04-27 |
| 18 | 201947019298-FORM 3 [20-10-2020(online)].pdf | 2020-10-20 |
| 19 | 201947019298-FORM 3 [19-04-2021(online)].pdf | 2021-04-19 |
| 20 | 201947019298-Information under section 8(2) [05-10-2021(online)].pdf | 2021-10-05 |
| 21 | 201947019298-FORM 3 [05-10-2021(online)].pdf | 2021-10-05 |
| 22 | 201947019298-FER.pdf | 2021-10-18 |
| 23 | 201947019298-FER_SER_REPLY [20-12-2021(online)].pdf | 2021-12-20 |
| 24 | 201947019298-DRAWING [20-12-2021(online)].pdf | 2021-12-20 |
| 25 | 201947019298-COMPLETE SPECIFICATION [20-12-2021(online)].pdf | 2021-12-20 |
| 26 | 201947019298-CLAIMS [20-12-2021(online)].pdf | 2021-12-20 |
| 27 | 201947019298-US(14)-HearingNotice-(HearingDate-03-03-2022).pdf | 2022-01-30 |
| 28 | 201947019298-REQUEST FOR ADJOURNMENT OF HEARING UNDER RULE 129A [24-02-2022(online)].pdf | 2022-02-24 |
| 29 | 201947019298-US(14)-ExtendedHearingNotice-(HearingDate-04-04-2022).pdf | 2022-03-14 |
| 30 | 201947019298-Correspondence to notify the Controller [28-03-2022(online)].pdf | 2022-03-28 |
| 31 | 201947019298-Information under section 8(2) [31-03-2022(online)].pdf | 2022-03-31 |
| 32 | 201947019298-FORM 3 [31-03-2022(online)].pdf | 2022-03-31 |
| 33 | 201947019298-Written submissions and relevant documents [13-04-2022(online)].pdf | 2022-04-13 |
| 34 | 201947019298-Annexure [13-04-2022(online)].pdf | 2022-04-13 |
| 35 | 201947019298-PatentCertificate25-04-2022.pdf | 2022-04-25 |
| 36 | 201947019298-IntimationOfGrant25-04-2022.pdf | 2022-04-25 |
| 37 | 201947019298-PROOF OF ALTERATION [21-12-2022(online)].pdf | 2022-12-21 |
| 38 | 201947019298-FORM-26 [12-01-2023(online)].pdf | 2023-01-12 |
| 39 | 201947019298-RELEVANT DOCUMENTS [11-09-2023(online)].pdf | 2023-09-11 |
| 40 | 201947019298-FORM-26 [28-12-2023(online)].pdf | 2023-12-28 |
| 1 | 2021-06-2308-19-31E_23-06-2021.pdf |