WO2002003961B1 - Microspheres and adjuvants for dna vaccine delivery - Google Patents
Microspheres and adjuvants for dna vaccine deliveryInfo
- Publication number
- WO2002003961B1 WO2002003961B1 PCT/US2001/021780 US0121780W WO0203961B1 WO 2002003961 B1 WO2002003961 B1 WO 2002003961B1 US 0121780 W US0121780 W US 0121780W WO 0203961 B1 WO0203961 B1 WO 0203961B1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- nucleic acid
- microspheres
- deliven
- dna
- acid molecules
- Prior art date
Links
- 239000004005 microsphere Substances 0.000 title claims abstract 14
- 239000002671 adjuvant Substances 0.000 title claims abstract 4
- 229960005486 vaccine Drugs 0.000 title 1
- 102000039446 nucleic acids Human genes 0.000 claims abstract 25
- 108020004707 nucleic acids Proteins 0.000 claims abstract 25
- 150000007523 nucleic acids Chemical class 0.000 claims abstract 25
- 238000000034 method Methods 0.000 claims abstract 11
- 229910019142 PO4 Inorganic materials 0.000 claims abstract 2
- -1 aminoalkyl glucosaminide Chemical class 0.000 claims abstract 2
- 238000005538 encapsulation Methods 0.000 claims abstract 2
- 239000010452 phosphate Substances 0.000 claims abstract 2
- 239000000839 emulsion Substances 0.000 claims 5
- 229920000642 polymer Polymers 0.000 claims 4
- 238000000605 extraction Methods 0.000 claims 3
- 208000035473 Communicable disease Diseases 0.000 claims 2
- 206010028980 Neoplasm Diseases 0.000 claims 2
- 201000011510 cancer Diseases 0.000 claims 2
- 230000008014 freezing Effects 0.000 claims 2
- 238000007710 freezing Methods 0.000 claims 2
- 208000015181 infectious disease Diseases 0.000 claims 2
- 239000000243 solution Substances 0.000 claims 2
- 239000002904 solvent Substances 0.000 claims 2
- 206010006187 Breast cancer Diseases 0.000 claims 1
- 208000026310 Breast neoplasm Diseases 0.000 claims 1
- 101100314454 Caenorhabditis elegans tra-1 gene Proteins 0.000 claims 1
- 239000002253 acid Substances 0.000 claims 1
- 239000007864 aqueous solution Substances 0.000 claims 1
- 150000001735 carboxylic acids Chemical group 0.000 claims 1
- 125000004185 ester group Chemical group 0.000 claims 1
- 239000003381 stabilizer Substances 0.000 claims 1
- 201000008827 tuberculosis Diseases 0.000 claims 1
- 102000053602 DNA Human genes 0.000 abstract 3
- 108020004414 DNA Proteins 0.000 abstract 3
- 230000003308 immunostimulating effect Effects 0.000 abstract 2
- 108010041986 DNA Vaccines Proteins 0.000 abstract 1
- 229940021995 DNA vaccine Drugs 0.000 abstract 1
- 238000004321 preservation Methods 0.000 abstract 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1641—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
- A61K9/1647—Polyesters, e.g. poly(lactide-co-glycolide)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
- A61P31/06—Antibacterial agents for tuberculosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Abstract
A nucleic acid delivery system that offers, in one system, a combination of high encapsulation efficiency, rapid release kinetics and preservation of DNA in supercoiled form is provided. The nucleic delivery system comprises nucleic acid molecules, such as deoxyribonucleic acid (DNA), encapsulated in biodegradable microspheres, and is particularly suited for delivery DNA vaccines. The ivnention futher provides a method for encapsulating nucleic acid molecules in microspheres. The invention additionally provides a composition comprising nucleic acid molecules encapsulated in microspheres produced by a method of the invention, and a method for delivering a nucleic acid molecule to a subject. The invention futher provides an adjuvant for modulating the immunostimulatory efficacy of microspheres encapsulating nucleic acid molecules comprising an aminoalkyl glucosaminide 4-phosphate (AGP). The invention also provides a method for modulating the immunostimulatory efficacy of microspheres encapsulating nucleic acid molecules.
Claims
1. A nucleic acid deliven7 system comprising deoxvπbonucleic acid (DNA) encapsulated in biodegradable polymeric microspheres, wherein the DNA is maintained above freezing temperature and below 37°C prior to the encapsulation, wherein at least 50% of the DNA compπses supercoiled DNA, and wherein at least 50% of the DNA is released from the microspheres after 7 days at about 37°C.
2. The nucleic acid dekverv system of claim 1 , wherein the microspheres have an encapsulauon efficiency of at least about 40%.
3. The nucleic acid deliven' system of claim 1 or 2, wherein at least about 70% of the DNA is released from the microspheres after 7 davs at about 37°C.
4. The nucleic acid deliven system of anv one of claims 1 to 3, wherein at least about 90° o of the microspheres are about 1 to about 10 μm in diameter.
5. The nucleic acid deliven- system of any one of claims 1 to 4, wherein the microspheres comprise poly(lacto-co-glvcolιde) (PLG).
6. The nucleic acid deliven system of anv one of claims 1 to 5, further comprising an adjuvant.
7. The nucleic acid deliven system of claim 6, wherein the adjuvant comprises an aminoalkyl glucosaminide 4-phosphate (AGP).
8. The nucleic acid deliven system of any one of claims 1 to 7, wherein the DNA encodes an anαgen associated with cancer or infectious disease.
9. The nucleic acid deliven system of claim 8, wherein the cancer is breast cancer.
10. The nucleic acid deliven system of claim 9, wherein the anαgen is her2/neu.
1. The nucleic acid deliver)' system of claim 8, wherein the infectious disease is tuberculosis.
12. The nucleic acid delιvenr system of claim 11, wherein the anUgen is TbH9.
13. A method for encapsulating nucleic acid molecules in microspheres comprising:
(a) dissolving a polymer in a solvent to form a polymer solution;
(b) adding an aqueous solution containing nucleic acid molecules to the polymer solution to form a primary emulsion;
(c) homogenizing the primary emulsion;
(d) mixing the priman' emulsion with a process medium comprising a stabilizer to form a secondary emulsion; and
(e) extracting the solvent from the secondary emulsion to form microspheres encapsulating nucleic acid molecules, wherein the nucleic acid molecules are maintained above freezing temperature and below 37°C prior to the extraction.
14. The method of claim 13, wherein the polymer comprises PLG.
15. The method of claim 14, wherein the PLG includes ester end groups or carboxylic acid end groups.
16. The method of claim 14 or 15, wherein the PLG has a molecular weight of from about 8 kDa to about 65 kDa.
17. The method of any one of claims 13 to 16, wherein the nucleic acid molecules are maintained at about 2°C to about 35°C prior to the extraction.
18. The method of claim 17, wherein the nucleic acid molecules are maintained at about 4°C to about 25°C prior to the extraction.
Priority Applications (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP01951039A EP1299087A1 (en) | 2000-07-07 | 2001-07-09 | Microspheres and adjuvants for dna vaccine delivery |
| CA002414926A CA2414926A1 (en) | 2000-07-07 | 2001-07-09 | Microspheres and adjuvants for dna vaccine delivery |
| AU2001271976A AU2001271976A1 (en) | 2000-07-07 | 2001-07-09 | Microspheres and adjuvants for dna vaccine delivery |
| JP2002508416A JP2004502721A (en) | 2000-07-07 | 2001-07-09 | Microspheres and adjuvants for DNA vaccine delivery |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US21660400P | 2000-07-07 | 2000-07-07 | |
| US60/216,604 | 2000-07-07 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| WO2002003961A1 WO2002003961A1 (en) | 2002-01-17 |
| WO2002003961B1 true WO2002003961B1 (en) | 2002-04-04 |
Family
ID=22807736
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/US2001/021780 WO2002003961A1 (en) | 2000-07-07 | 2001-07-09 | Microspheres and adjuvants for dna vaccine delivery |
Country Status (6)
| Country | Link |
|---|---|
| US (2) | US20020032165A1 (en) |
| EP (1) | EP1299087A1 (en) |
| JP (1) | JP2004502721A (en) |
| AU (1) | AU2001271976A1 (en) |
| CA (1) | CA2414926A1 (en) |
| WO (1) | WO2002003961A1 (en) |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20030139356A1 (en) * | 2001-05-18 | 2003-07-24 | Persing David H. | Prophylactic and therapeutic treatment of infectious and other diseases with mono- and disaccharide-based compounds |
| WO2003005952A2 (en) | 2001-07-10 | 2003-01-23 | Corixa Corporation | Compositions and methods for delivery of proteins and adjuvants encapsulated in microspheres |
| GB0201736D0 (en) * | 2002-01-25 | 2002-03-13 | Glaxo Group Ltd | DNA dosage forms |
| JP2005525344A (en) * | 2002-02-04 | 2005-08-25 | コリクサ コーポレイション | Immunostimulatory composition comprising aminoalkyl glucosaminide phosphate and saponin |
| US7094410B2 (en) * | 2002-03-02 | 2006-08-22 | The Scripps Research Institute | DNA vaccine against proliferating endothelial cells and methods of use thereof |
| US6923958B2 (en) | 2002-03-02 | 2005-08-02 | The Scripps Research Institute | DNA vaccines encoding CEA and a CD40 ligand and methods of use thereof |
| EP1549352A4 (en) * | 2002-05-06 | 2005-07-27 | Nucleonics Inc | Methods for delivery of nucleic acids |
| GB0228689D0 (en) * | 2002-12-09 | 2003-01-15 | Elan Drug Delivery Ltd | Compositions |
| US7053783B2 (en) | 2002-12-18 | 2006-05-30 | Biovigilant Systems, Inc. | Pathogen detector system and method |
| WO2004060396A2 (en) | 2002-12-27 | 2004-07-22 | Chiron Corporation | Immunogenic compositions containing phospholpid |
| MXPA05012270A (en) * | 2003-05-12 | 2006-02-10 | Univ Florida | Materials and methods for immunizing against fiv infection. |
| US7658927B2 (en) * | 2003-05-12 | 2010-02-09 | University Of Florida Research Foundation, Inc. | Materials and methods for immunizing against FIV infection |
| SE527505C2 (en) * | 2003-06-10 | 2006-03-28 | Anna Imberg | Composite materials and particles |
| JP4871868B2 (en) | 2004-07-30 | 2012-02-08 | バイオヴィジラント システムズ インコーポレイテッド | Pathogen and particulate detection system and detection method |
| EP1907818A4 (en) * | 2005-07-15 | 2012-03-14 | Biovigilant Systems Inc | Pathogen and particle detector system and method |
| US8628976B2 (en) * | 2007-12-03 | 2014-01-14 | Azbil BioVigilant, Inc. | Method for the detection of biologic particle contamination |
| CN104981236B (en) * | 2012-09-27 | 2019-01-22 | 珠海圣美生物诊断技术有限公司 | Stimulate sensibility particle and application method |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2050911C (en) * | 1989-05-04 | 1997-07-15 | Thomas R. Tice | Encapsulation process and products therefrom |
| ATE359831T1 (en) * | 1997-01-22 | 2007-05-15 | Zycos Inc | MICROPARTICLES FOR ADMINISTRATION OF NUCLEIC ACIDS |
| US6048551A (en) * | 1997-03-27 | 2000-04-11 | Hilfinger; John M. | Microsphere encapsulation of gene transfer vectors |
| US6197229B1 (en) * | 1997-12-12 | 2001-03-06 | Massachusetts Institute Of Technology | Method for high supercoiled DNA content microspheres |
| GB9810236D0 (en) * | 1998-05-13 | 1998-07-08 | Microbiological Res Authority | Improvements relating to encapsulation of bioactive agents |
-
2001
- 2001-07-09 AU AU2001271976A patent/AU2001271976A1/en not_active Abandoned
- 2001-07-09 CA CA002414926A patent/CA2414926A1/en not_active Abandoned
- 2001-07-09 WO PCT/US2001/021780 patent/WO2002003961A1/en not_active Application Discontinuation
- 2001-07-09 EP EP01951039A patent/EP1299087A1/en not_active Withdrawn
- 2001-07-09 JP JP2002508416A patent/JP2004502721A/en active Pending
- 2001-07-09 US US09/901,829 patent/US20020032165A1/en not_active Abandoned
-
2003
- 2003-04-22 US US10/420,482 patent/US20040009941A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| JP2004502721A (en) | 2004-01-29 |
| AU2001271976A1 (en) | 2002-01-21 |
| WO2002003961A1 (en) | 2002-01-17 |
| EP1299087A1 (en) | 2003-04-09 |
| CA2414926A1 (en) | 2002-01-17 |
| US20020032165A1 (en) | 2002-03-14 |
| US20040009941A1 (en) | 2004-01-15 |
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