Vaccine nanotechnology

• US 9,474,717 B2
• Filed: 03/15/2013
• Issued: 10/25/2016
• 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): Long, Scott
• Application Number:
  US13/844,100
• Publication Number:
  US 20130287857A1
• Time in Patent Office: 1,320 Days
• 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 formed of linear, branched, or dendrimeric polymer selected from the group consisting of polyanhydrides, polyhydroxyacids, polyesters and copolymers thereof, having a mean diameter of between 60 nm and 400 nm, the nanoparticles comprising:

T cell antigen selected from the group consisting of infectious disease antigens, cancer antigens, atopic disease antigens, alloantigens, and hapten, and

an immunostimmulatory agent effective to enhance the immune response to the T cell antigen,

wherein the immunostimulatory agent is selected from the group consisting of toll-like receptor (TLR) agonists, cytokine receptor agonists, CD40 agonists, Fc receptor agonists, CpG-containing nucleic acids, complement receptor agonists,

wherein the T cell antigen is encapsulated within, and/or covalently bound to the polymer forming the nanoparticles

and

wherein the immunostimulatory agent is covalently bound to the nanoparticles or to a polymer from which the nanoparticles are formed.

2. The nanoparticles of claim 1, wherein the nanoparticles comprise B cell antigen bound to or present on the surface of the nanoparticles in a density effective to activate B cell receptors, B cell antigen encapsulated within the nanoparticles, or any combination thereof.

3. The nanoparticles of claim 1, wherein the T cell antigen is a cancer antigen.

4. The nanoparticles of claim 1, wherein the infectious disease antigen is a viral antigen.

5. The nanoparticles of claim 4, wherein the viral antigen is an antigen from a pox virus, smallpox virus, ebola virus, marburg virus, dengue fever virus, influenza virus, parainfluenza virus, respiratory syncytial virus, rubeola virus, human immunodeficiency virus, human papillomavirus, varicella-zoster virus, herpes simplex virus, cytomegalovirus, Epstein-Barr virus, JC virus, rhabdovirus, rotavirus, rhinovirus, adenovirus, papillomavirus, parvovirus, picornavirus, poliovirus, virus that causes mumps, virus that causes rabies, reovirus, rubella virus, togavirus, orthomyxovirus, retrovirus, hepadnavirus, coxsackievirus, equine encephalitis virus, Japanese encephalitis virus, yellow fever virus, Rift Valley fever virus, hepatitis A virus, hepatitis B virus, hepatitis C virus, hepatitis D virus, or hepatitis E virus.

6. The nanoparticles of claim 3, wherein the cancer antigen is selected from the group consisting of melan-A, dipeptidyl peptidase IV, adenosine deaminase-binding protein, cyclophilin b, the colorectal cancer antigen C017-1A/GA733, the carcinoembryonic antigen (CEA) and its immunogenic epitopes CAP-1 and CAP-2, etv6, aml1, prostate specific antigen (PSA) and its immunogenic epitopes PSA-1, PSA-2, and PSA-3, prostate-specific membrane antigen (PSMA), T-cell receptor/CD3-zeta chain, the MAGE-family of tumor antigens, the GAGE-family of tumor antigens, BAGE, RAGE, LAGE-1, NAG, GnT-V, MUM-1, CDK4, tyrosinase, p53, MUC family of tumor antigens, HER2/neu, p21ras, RCAS1, α

-fetoprotein, E-cadherin, α

-catenin, β

-catenin and γ

-catenin, p120ctn, gp100Pme1117, FRAME, NY-ESO-1, brain glycogen phosphorylase, SSX-1, SSX-2, SSX-1, SSX-4, SSX-5, SCP-1, CT-7, cdc27, adenomatous polyposis coli protein (APC), fodrin, P1A, Connexin 37, Ig-idiotype, p15, gp75, GM2 and GD2 gangliosides, viral products such as human papilloma virus proteins, Smad family of tumor antigens, lmp-1, EBV-encoded nuclear antigen (EBNA)-1, and c-erbB-2.

7. The nanoparticles of claim 1, wherein the nanoparticles further comprise a targeting moiety

associated covalently or non-covalently with the surface of the nanoparticles.

8. The nanoparticles of claim 1, formed of one or more polymers, wherein the one or more polymers is a water soluble, non-adhesive polymer, wherein the water soluble, non-adhesive polymer is a polyalkylene oxide.

9. The nanoparticles of claim 1, wherein the nanoparticles comprise a copolymer of a water soluble, non-adhesive polymer and a biodegradable polymer.

11. The nanoparticles of claim 9, wherein the nanoparticles are formed by self-assembly.

12. The nanoparticles of claim 8, wherein the polyalkylene oxide is a polyalkylene glycol.

10. The nanoparticles of claim DU 9, wherein the biodegradable polymer is poly(lactic acid) (PLA), poly(glycol) (PGA) or poly(lactide-co-glycolic) (PLGA).