Vaccine nanotechnology

• US 9,526,702 B2
• Filed: 03/15/2013
• Issued: 12/27/2016
• Est. Priority Date: 10/12/2007
• Status: Active Grant

• Current Assignee: Children's Medical Center Corporation, Massachusetts Institute of Technology
• Original Assignee: Brigham and Women's Hospital Incorporated, Children's Medical Center Corporation, President and Fellows of Harvard College (Harvard Corporation), Massachusetts Institute of Technology
• Inventors: von Andrian, Ulrich H., Farokhzad, Omid C., Langer, Robert S., Junt, Tobias, Moseman, Elliott Ashley, Zhang, Liangfang, Basto, Pamela, Iannacone, Matteo, Alexis, Frank
• Primary Examiner(s): EPPS -SMITH, JANET L
• Application Number:
  US13/844,258
• Publication Number:
  US 20130236533A1
• Time in Patent Office: 1,383 Days
• Field of Search: 424/184.1, 424/450, 424/489
• US Class Current: 1/1
• CPC Class Codes: A61K 2039/555 characterised by a specific combination antigen/adjuvant
• CPC Class Codes: A61K 2039/55555 Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers
• CPC Class Codes: A61K 2039/60 characteristics by the carrier linked to the antigen
• CPC Class Codes: A61K 39/00 Medicinal preparations containing antigens or antibodies materials for immunoassay G01N33/53
• CPC Class Codes: A61K 39/0011 Cancer antigens
• CPC Class Codes: A61K 39/001102 Receptors, cell surface antigens or cell surface determinants
• CPC Class Codes: A61K 39/001106 Her-2/neu/ErbB2, Her-3/ErbB3 or Her 4/ErbB4
• CPC Class Codes: A61K 39/001151 p53
• CPC Class Codes: A61K 39/001156 Tyrosinase and tyrosinase related proteinases [TRP-1 or TRP-2]
• CPC Class Codes: A61K 39/001158 Proteinases
• CPC Class Codes: A61K 39/001162 Kinases, e.g. Raf or Src
• CPC Class Codes: A61K 39/001166 Adhesion molecules, e.g. NRCAM, EpCAM or cadherins
• CPC Class Codes: A61K 39/00117 Mucins, e.g. MUC-1
• CPC Class Codes: A61K 39/001171 Gangliosides, e.g. GM2, GD2 or GD3
• CPC Class Codes: A61K 39/001181 Alpha-feto protein
• CPC Class Codes: A61K 39/001182 Carcinoembryonic antigen [CEA]
• CPC Class Codes: A61K 39/001184 Cancer testis antigens, e.g. SSX, BAGE, GAGE or SAGE
• CPC Class Codes: A61K 39/001186 MAGE
• CPC Class Codes: A61K 39/001188 NY-ESO
• CPC Class Codes: A61K 39/001191 Melan-A/MART
• CPC Class Codes: A61K 39/001194 : Prostate specific antigen [PSA]
• CPC Class Codes: A61K 39/001195 : Prostate specific membrane antigen [PSMA]
• CPC Class Codes: A61K 39/12 : Viral antigens
• CPC Class Codes: A61K 39/39 : characterised by the immunostimulating additives, e.g. chemical adjuvants
• CPC Class Codes: A61K 47/6911 : the form being a liposome
• CPC Class Codes: A61K 47/6937 : the polymer being PLGA, PLA or polyglycolic acid
• CPC Class Codes: A61K 9/14 : Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles microspheres A61K9/16; microcapsules A61K9/50; nanocapsules, nanoparticles of the matrix type A61K9/51
• CPC Class Codes: A61P 1/04 : for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 11/06 : Antiasthmatics
• CPC Class Codes: A61P 17/00 : Drugs for dermatological disorders
• CPC Class Codes: A61P 17/02 : for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 19/02 : for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 25/00 : Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/30 : for treating abuse or dependence
• CPC Class Codes: A61P 29/00 : Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/00 : Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/10 : for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/00 : Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 : Antibacterial agents
• CPC Class Codes: A61P 31/06 : for tuberculosis
• CPC Class Codes: A61P 31/10 : Antimycotics
• CPC Class Codes: A61P 31/12 : Antivirals
• CPC Class Codes: A61P 31/14 : for RNA viruses
• CPC Class Codes: A61P 31/16 : for influenza or rhinoviruses
• CPC Class Codes: A61P 31/18 : for HIV
• CPC Class Codes: A61P 33/00 : Antiparasitic agents
• CPC Class Codes: A61P 33/02 : Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
• CPC Class Codes: A61P 33/06 : Antimalarials
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 37/00 : Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 : Immunomodulators
• CPC Class Codes: A61P 37/04 : Immunostimulants
• CPC Class Codes: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 37/08 : Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 5/00 : Drugs for disorders of the endocrine system
• CPC Class Codes: A61P 5/14 : of the thyroid hormones, e.g. T3, T4
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: Y02A 50/30 : Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The present invention provides compositions and systems for delivery of nanocarriers to cells of the immune system. The invention provides vaccine nanocarriers capable of stimulating an immune response in T cells and/or B cells, in some embodiments, comprising at least one immunomodulatory agent, and optionally comprising at last one targeting moiety and optionally at least one immunostimulatory agent. The invention provides pharmaceutical compositions comprising inventive vaccine nanocarriers. The present invention provides methods of designing, manufacturing, and using inventive vaccine nanocarriers and pharmaceutical compositions thereof. The invention provides methods of prophylaxis and/or treatment of diseases, disorders, and conditions comprising administering at least one inventive vaccine nanocarrier to a subject in need thereof.

Claims

1. Nanoparticles having a geometric diameter of between greater than 60 nm and less than 250 nm, and formed of one or more polymers selected from the group consisting of polyesters, polyhydroxacids, poly(orthoesters);

polyanhydrides, polyalkylene oxides, and copolymers thereof,

wherein the nanoparticles selectively target the subcapsular macrophages and dendritic cells in the draining lymph nodes, and

wherein the nanoparticles comprise

a dendritic cell immunomodulatory agent selected from the group consisting of toll-like receptor agonists, CD40 agonists, and agents which promote dendritic cell maturation; and

a T cell peptide antigen for processing by dendritic cells and presentation with major histocompatibility complex (MHC) to T cells.

2. The nanoparticles of claim 1, wherein the immunomodulatory agent is covalently associated with the nanoparticle.

3. The nanoparticles of claim 1, wherein the immunomodulatory agent is non-covalently associated with the nanoparticle.

4. The nanoparticles of claim 1, wherein the nanoparticles comprise a lipid membrane.

5. The nanoparticles of claim 1, wherein the polymer is an amphiphilic polymer.

6. The nanoparticles of claim 5, wherein the hydrophobic end of the amphiphilic polymer is located within the interior of the nanoparticles.

7. The nanoparticles of claim 1, comprising an amphiphilic entity selected from the group consisting of phosphatidylcholine, lipid A, cholesterol, dolichol, sphingosine, sphingomyelin, ceramide, cerebroside, sulfatide, phytosphingosine, phosphatidylethanolamine, glycosylceramide, phosphatidylglycerol, phosphatidylinositol, phosphatidylserine, cardiolipin, phosphatidic acid, and lysophosphatides.

8. The nanoparticles of claim 1, wherein the T cell antigen is a degenerative disease antigen, an infectious disease antigen, or a cancer antigen.

9. The nanoparticles of claim 1, wherein the immunomodulatory agent is a CpG-containing immunomodulatory nucleic acid.

10. The nanoparticles of claim 1 wherein the T cell antigen is covalently bound to the nanoparticles or to a polymer from which the nanoparticles are formed.

11. The nanoparticles of claim 1 further comprising a dendritic cell targeting agent selected from the group consisting of CD11b;

CD169;

mannose receptor;

DC-205, CD11c;

BDCA-1;

BDCA-2;

BDCA-4;

class II MHC;

CD80;

CD86;

DC-SIGN;

Siglec-H;

CX3 CR1; and

CD21/35.

12. The nanoparticles of claim 1, wherein the immunomodulatory agent targets the nanoparticles to secondary lymphoid tissue or organs.

13. The nanoparticles of claim 1 wherein the immunomodulatory agent is on the surface of the nanoparticle, encapsulated within the nanoparticle, or both on the surface and encapsulated within the nanoparticle.

14. The nanoparticles of claim 1, wherein the immunomodulatory agent is a toll-like receptor agonist.

15. The nanoparticles of claim 1 having encapsulated therein T cell antigen in combination with an immunomodulatory agent.

16. The nanoparticles of claim 1 formed of a hydrophobic polymer providing a hydrophobic environment within the nanoparticles.

17. The nanoparticles of claim 1, wherein the copolymer is made from poly(lactide-co-glycolide) and polyethylene glycol.

18. The nanoparticles of claim 1, wherein the nanoparticles have a positive zeta potential.

19. The nanoparticles of claim 1, wherein the nanoparticle forms by self-assembly.

20. The nanoparticles of claim 1, wherein the zeta potential is between −

25 mV and +25 mV.

21. The nanoparticles of claim 1, wherein the immunomodulatory agent is less than 20% by weight of the nanoparticle.