CA2166208A1 - Phosphazene polyelectrolytes as immunoadjuvants - Google Patents

Phosphazene polyelectrolytes as immunoadjuvants

Info

Publication number
CA2166208A1
CA2166208A1 CA002166208A CA2166208A CA2166208A1 CA 2166208 A1 CA2166208 A1 CA 2166208A1 CA 002166208 A CA002166208 A CA 002166208A CA 2166208 A CA2166208 A CA 2166208A CA 2166208 A1 CA2166208 A1 CA 2166208A1
Authority
CA
Canada
Prior art keywords
aliphatic
composition
group
antigen
polyphosphazene
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CA002166208A
Other languages
French (fr)
Other versions
CA2166208C (en
Inventor
Alexander K. Andrianov
Sharon A. Jenkins
Lendon G. Payne
Bryan E. Roberts
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Celldex Therapeutics Inc
Original Assignee
Individual
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Individual filed Critical Individual
Publication of CA2166208A1 publication Critical patent/CA2166208A1/en
Application granted granted Critical
Publication of CA2166208C publication Critical patent/CA2166208C/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/385—Haptens or antigens, bound to carriers
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G79/00—Macromolecular compounds obtained by reactions forming a linkage containing atoms other than silicon, sulfur, nitrogen, oxygen, and carbon with or without the latter elements in the main chain of the macromolecule
    • C08G79/02—Macromolecular compounds obtained by reactions forming a linkage containing atoms other than silicon, sulfur, nitrogen, oxygen, and carbon with or without the latter elements in the main chain of the macromolecule a linkage containing phosphorus
    • C08G79/025—Polyphosphazenes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/39—Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/54—Medicinal preparations containing antigens or antibodies characterised by the route of administration
    • A61K2039/541—Mucosal route
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
    • A61K2039/55511—Organic adjuvants
    • A61K2039/55555—Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

An immunoadjuvant soluble polyphosphazene polyelectrolyte is disclosed. In one embodiment, the polymeric adjuvant is a poly(organophosphazene) with (i) ionized or ionizable pendant groups that contain, for example, carboxylic acid, sulfonic acid, or hydroxyl moieties, and (ii) pendant groups that are susceptible to hydrolysis under the conditions of use, to impart biodegradability to the polymer.

Claims (37)

1. A vaccine composition comprising a watersoluble polyphosphazene polyelectrolyte in combination with an antigen.
2. The composition of claim 1 wherein the polyphosphazene polyelectrolyte is of the formula wherein A and B can vary independently in the polymer, and can be:
(i) a group that is susceptible to hydrolysis under the conditions of use; or (ii) a group that is not susceptible to hydrolysis under the conditions of use selected from the group consisting of aliphatic, aryl, aralkyl, alkaryl, carboxylic acid, heteroaromatic, heteroalkyl, (aliphatic)amino-, heteroaralkyl, di(aliphatic)aminoarylamino-, diarylamino-, alkylarylamino-, -oxyaryl, -oxyphenylCO2H, -oxyphenylSO3H, -oxyphenylhydroxyl, -oxyphenylPO3H, -oxyaliphatic, -oxyalkyl, -oxy(aliphatic)CO2H, -oxy(aliphatic)SO3H, -oxy(aliphatic)PO3H, -oxy(aliphatic)hydroxyl, -oxyalkaryl, -oxyaralkyl, -thioaryl, -thioaliphatic, -thioalkaryl, thioaralkyl, or -NHC(O)O-(aryl or aliphatic), -O-[(CH2)xO]y-(CH2)xNH2 -O-[(CH2)xO]y(CH2)xNH(CH2)xSO3H, and -O-[(CH2)xO]y-(aryl or aliphatic), wherein x is 1-8 and y is an integer of 1 to 20;
and wherein n is an interger.
3. The composition of claim 2, wherein the polymer contains at least 10 percent or more of repeating units that are not susceptible to hydrolysis under the conditions of use.
4. The composition of claim 2, wherein the polymer contains at least 90 percent or more of repeating units that are not susceptible to hydrolysis under the conditions of use.
5. The composition of claim 2, wherein the hydrolyzable groups are independently selected from the group consisting of chlorine, amino acid or amino acid ester (bound through the amino group), imidazole, glycerol, and glucosyl.
6. The composition of claim 1 wherein the polyphosphazene polyelectrolyte is biodegradable.
7. The composition of claim 1 wherein the polyphosphazene is mixed with the antigen.
8. The composition of claim 8 wherein the polyphosphazene polyelectrolyte is cross-linked with a multivalent cation.
9. The composition of claim 8 wherein the multivalent cation is selected from the group consisting of calcium, copper, aluminum, magnesium, strontium, barium, tin, zinc, iron, poly(amino acid), poly(ethyleneimine), poly(vinylamine) and polysaccharides.
10. The composition of claim 1 wherein the antigen is selected from the group consisting of a compound derived from a cell, bacteria, or virus particle, or portion thereof, wherein the compound is selected from the group consisting of proteins, peptides, polysaccharides, glycoproteins, glycolipids, nucleic acid, or combinations thereof.
11. The composition of claim 10 wherein the antigen is selected from the group consisting of influenza proteins, human immunodeficiency virus (HIV) proteins, hepatitis B
proteins, bacterial proteins and bacterial lipopoly-saccharides.
12. The composition of claim 1 wherein the polyphosphazene polyelectrolyte is covalently conjugated with the antigen.
13. The composition of claim 2 wherein the polypphosphazene polyelectrolyte is a phosphazene that has acidic side chains selected from the group consisting of carboxylic acid, sulfonic acid, and hydroxyl groups.
14. The composition of claim 10 wherein the phosphazene polyelectrolyte is biodegradable.
15. The composition of claim 1 for oral delivery.
16. The composition of claim 1 for delivery to the nasal associated lymphoid tissue.
17. The composition of claim 1 for delivery to therectum.
18. The composition of claim 1 for delivery to the
19. A method of causing an immune response in an animal comprising the steps of administering to the animal an antigen in combination with a water-soluble polyphosphazene polyelectrolyte.
20. The method of claim 19, wherein the antigen is conjugated with the polyphosphazene polyelectrolyte.
21. The method of claim 19 wherein the antigen and polyphosphazene are administered separately to proximate sites.
22. The method of claim 19 wherein the antigen and polyphosphazene are first combined and the combination is administered to the animal.
23. The method of claim 19 wherein the method of administration is parenteral.
24. The method of claim 19 wherein the method of administration is oral.
25. The method of claim 19 wherein the polyphosphazene polyelectrolyte is of the formula wherein A and B can vary independently in the polymer, and can be:
(i) a group that is susceptible to hydrolysis under the conditions of use; or (ii) a group that is not susceptible to hydrolysis under the conditions of use selected from the group consisting of aliphatic, aryl, aralkyl, alkaryl, carboxylic acid, heteroaromatic, heteroalkyl, (aliphatic)amino-, heteroaralkyl, di(aliphatic)aminoarylamino-, diarylamino-, alkylarylamino-, -oxyaryl, -oxyphenylCO2H, -oxyphenylSO3H, -oxyphenylhydroxyl, -oxyphenylPO3H, -oxyaliphatic, -oxyalkyl, -oxy(aliphatic)CO2H, -oxy(aliphatic)SO3H, -oxy(aliphatic)PO3H, -oxy(aliphatic)hydroxyl, -oxyalkaryl, -oxyaralkyl, -thioaryl, -thioaliphatic, -thioalkaryl, thioaralkyl, -NHC(O)O-(aryl or aliphatic), -O-[(CH2)xO]y-CH2) -O-[(CH2)xO]yCH2)xNH(CH2)xSO3H, or -O-[(CH2)xO]y-(aryl or aliphatic), wherein x is 1-8 and y wherein n is an integer.
26. The method of claim 25, wherein the polymer contains at least 10 percent or more of repeating units that are not susceptible to hydrolysis under the conditions of use.
27. The method of claim 25, wherein the polymer contains at least 90 percent or more of repeating units 'hat are not susceptible to hydrolysis under the conditions of use.
28. The method of claim 19 wherein the polyphosphazene polyelectrolyte is biodegradable.
29. The method of claim 28 wherein the polyphosphazene polyelectrolyte contains hydrolyzable side chains selected from the group consisting of amino acid, amino acid ester, chlorine, imidazole, glycerol, and glucosyl.
30. The method of claim 19 wherein the polyphosphazene polyelectrolyte is cross-linked by a multivalent cation.
31. The method of claim 19 wherein the polyphosphazene polyelectrolyte is physically mixed with the antigen.
32. The method of claim 19 wherein the antigen is selected from the group consisting of a compound derived from a cell, bacteria, or virus particle, or portion thereof, wherein the compound is selected from the group consisting of proteins, peptides, polysaccharides, glycoproteins, glycolipids, nucleic acid, or combinations thereof.
33. The method of claim 32 wherein the antigen is selected from the group consisting of influenza proteins, human immunodeficiency virus (HIV) proteins, hepatitis B
proteins, bacterial proteins and bacterial lipopolysaccharides.
34. The method of claim 19 for oral delivery.
35. The method of claim 19 for delivery to the nasal associated lymphoid tissue.
36. The method of claim 19 for delivery to the respiratory tract.
37. The method of claim 19 for delivery to the rectum.
CA2166208A 1993-07-12 1994-07-08 Phosphazene polyelectrolytes as immunoadjuvants Expired - Fee Related CA2166208C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US08/090,841 1993-07-12
US08/090,841 US5562909A (en) 1993-07-12 1993-07-12 Phosphazene polyelectrolytes as immunoadjuvants
PCT/US1994/007665 WO1995002415A1 (en) 1993-07-12 1994-07-08 Phosphazene polyelectrolytes as immunoadjuvants

Publications (2)

Publication Number Publication Date
CA2166208A1 true CA2166208A1 (en) 1995-01-26
CA2166208C CA2166208C (en) 2010-04-20

Family

ID=22224581

Family Applications (1)

Application Number Title Priority Date Filing Date
CA2166208A Expired - Fee Related CA2166208C (en) 1993-07-12 1994-07-08 Phosphazene polyelectrolytes as immunoadjuvants

Country Status (16)

Country Link
US (3) US5562909A (en)
EP (1) EP0710117B1 (en)
JP (1) JPH09500629A (en)
KR (2) KR100352336B1 (en)
CN (1) CN1134265C (en)
AT (1) ATE207505T1 (en)
AU (1) AU691824B2 (en)
BR (1) BR9407051A (en)
CA (1) CA2166208C (en)
DE (1) DE69428795T2 (en)
DK (1) DK0710117T3 (en)
ES (1) ES2166376T3 (en)
NZ (1) NZ269396A (en)
PT (1) PT710117E (en)
SG (1) SG46659A1 (en)
WO (2) WO1995002415A1 (en)

Families Citing this family (147)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5643578A (en) * 1992-03-23 1997-07-01 University Of Massachusetts Medical Center Immunization by inoculation of DNA transcription unit
US5855895A (en) * 1995-06-07 1999-01-05 Virus Research Institute Polyphosphazene polyelectrolyte immunoadjuvants
AU738698B2 (en) * 1994-07-08 2001-09-27 Avant Immunotherapeutics, Inc. Polyphosphazene polyelectrolyte immunoadjuvants
FR2732605B1 (en) * 1995-04-07 1997-05-16 Pasteur Merieux Serums Vacc COMPOSITION FOR INDUCING MUCOSAL IMMUNE RESPONSE
US6428771B1 (en) * 1995-05-15 2002-08-06 Pharmaceutical Discovery Corporation Method for drug delivery to the pulmonary system
US5891444A (en) * 1995-06-07 1999-04-06 Virus Research Institute, Inc. HIV-1 prophylactic composition and method
US5900238A (en) * 1995-07-27 1999-05-04 Immunex Corporation Vaccine delivery system
US5914231A (en) * 1995-08-17 1999-06-22 Universiteit Utrecht Introgene B.V. Poly(organo)phosphazenes for use in synthetic transfection systems
EP0965336A1 (en) * 1995-11-09 1999-12-22 Microbiological Research Authority Microencapsulated DNA for gene therapy
US6126964A (en) * 1996-01-04 2000-10-03 Mirus Corporation Process of making a compound by forming a polymer from a template drug
US5898062A (en) * 1996-04-10 1999-04-27 The Penn State Research Foundation Poly (organophosphazene) hydrogels
US5807757A (en) * 1996-07-02 1998-09-15 Virus Research Institute, Inc. Preparation of ionically cross-linked polyphosphazene microspheresy by coacervation
US6303300B1 (en) * 1996-08-16 2001-10-16 Introgen B.V. Poly (organo) phosphazenes for use in synthetic transfection systems
US5858389A (en) * 1996-08-28 1999-01-12 Shaker H. Elsherbini Squalene is an antiviral compound for treating hepatitis C virus carriers
US6077662A (en) * 1996-11-27 2000-06-20 Emory University Virus-like particles, methods and immunogenic compositions
AU7563798A (en) * 1997-04-30 1998-11-24 Emory University Methods and compositions for administering dna to mucosal surfaces
US6077916A (en) * 1997-06-04 2000-06-20 The Penn State Research Foundation Biodegradable mixtures of polyphoshazene and other polymers
US5760271A (en) * 1997-08-18 1998-06-02 Virus Research Institute, Inc. Production of polyorganophosphazenes
WO1999009956A1 (en) * 1997-08-29 1999-03-04 Corixa Corporation Rapid release encapsulated bioactive agents for inducing or potentiating an immune response and methods of using thereof
US5958414A (en) * 1997-09-03 1999-09-28 Heska Corporation Composition to protect a mammal against Bartonella henselae infection
US6726934B1 (en) 1997-10-09 2004-04-27 Vanderbilt University Micro-particulate and nano-particulate polymeric delivery system
EP1021168A4 (en) * 1997-10-09 2006-08-30 Univ Vanderbilt Micro-particulate and nano-particulate polymeric delivery system
US6969520B2 (en) 1997-10-20 2005-11-29 Acambis Inc. Active immunization against clostridium difficile disease
DE69829400T2 (en) 1997-10-20 2006-04-13 Acambis, Inc., Cambridge PASSIVE IMMUNIZATION AGAINST CLOSTRIDIUM DIFFICILE DISEASE
US6207171B1 (en) * 1998-03-27 2001-03-27 Avant Immunotherapeutics, Inc. Polyphosphazene microspheres
SE9801288D0 (en) 1998-04-14 1998-04-14 Astra Ab Vaccine delivery system and method of production
US6506385B1 (en) 1998-04-17 2003-01-14 Embrex, Inc. Live vaccines and methods of treatment therewith
WO1999058134A1 (en) * 1998-05-11 1999-11-18 Purdue Research Foundation Methods and compositions for nucleic acid delivery
US6368625B1 (en) 1998-08-12 2002-04-09 Cima Labs Inc. Orally disintegrable tablet forming a viscous slurry
US7087236B1 (en) * 1998-09-01 2006-08-08 Merrion Research I Limited Method for inducing a cell-mediated immune response and improved parenteral vaccine formulations thereof
US6696089B2 (en) 1998-09-03 2004-02-24 Board Of Regents Of The University Of Nebraska Nanogel networks including polyion polymer fragments and biological agent compositions thereof
US6333051B1 (en) * 1998-09-03 2001-12-25 Supratek Pharma, Inc. Nanogel networks and biological agent compositions thereof
US5952232A (en) * 1998-09-17 1999-09-14 Rothman; James Edward Expandible microparticle intracellular delivery system
US6261573B1 (en) * 1998-10-30 2001-07-17 Avant Immunotherapeutics, Inc. Immunoadjuvants
ATE422364T1 (en) * 1998-12-17 2009-02-15 Sanofi Pasteur Ltd MULTIVALENT IMMUNOGENIC COMPOSITION CONTAINING AN RSV SUBUNIT COMPOSITION AND AN INFLUENZA VIRUS PREPARATION
AU3347000A (en) 1999-01-19 2000-08-01 Children's Hospital Of Philadelphia, The Hydrogel compositions for controlled delivery of virus vectors and methods of use thereof
US6586501B1 (en) 1999-01-20 2003-07-01 Cabot Corporation Aggregates having attached polymer groups and polymer foams
US6258864B1 (en) 1999-01-20 2001-07-10 Cabot Corporation Polymer foam containing chemically modified carbonaceous filler
AT407958B (en) * 1999-02-11 2001-07-25 Immuno Ag INACTIVATED INFLUENZA VIRUS VACCINE FOR NASAL OR ORAL APPLICATION
US6521431B1 (en) * 1999-06-22 2003-02-18 Access Pharmaceuticals, Inc. Biodegradable cross-linkers having a polyacid connected to reactive groups for cross-linking polymer filaments
WO2001001964A2 (en) 1999-06-23 2001-01-11 Sedum Laboratories, Inc. Ionically formulated biomolecule microcarriers
PT1196430E (en) * 1999-06-29 2012-04-18 Mannkind Corp Purification and stabilization of peptide and protein pharmaceutical agents
US9006175B2 (en) * 1999-06-29 2015-04-14 Mannkind Corporation Potentiation of glucose elimination
US20020009466A1 (en) * 1999-08-31 2002-01-24 David J. Brayden Oral vaccine compositions
WO2001015727A2 (en) * 1999-09-02 2001-03-08 Antigenics Inc. Compositions of immunostimulatory polymers and saponin adjuvants and uses thereof
DE60038971D1 (en) 1999-10-22 2008-07-03 Aventis Pasteur PROCESS FOR EXPLORING AND / OR REINFORCING THE IMMUNE RESPONSE AGAINST TUMORANTIGENE
GB0000001D0 (en) * 2000-01-05 2000-02-23 Du Pont Uk Pharmaceutical compositions and their preparation
CA2408997C (en) 2000-04-11 2008-08-05 Universitat Heidelberg Poly-tri-fluoro-ethoxypolyphosphazene coverings and films for medical devices
EP1792995A3 (en) 2000-05-08 2007-06-13 Sanofi Pasteur Limited Chlamydia secretory locus orf and uses thereof
EP1282702B1 (en) 2000-05-10 2006-11-29 Sanofi Pasteur Limited Immunogenic polypeptides encoded by mage minigenes and uses thereof
US6605237B2 (en) * 2000-06-29 2003-08-12 The Penn State Research Foundation Polyphosphazenes as gel polymer electrolytes
US6740409B1 (en) * 2000-11-15 2004-05-25 Board Of Trustees Of University Of Illinois Polymer films
DE10100961B4 (en) 2001-01-11 2005-08-04 Polyzenix Gmbh Body-compatible material and substrate coated with this material for the cultivation of cells and artificial organic implants constructed or grown from cells
US9080146B2 (en) 2001-01-11 2015-07-14 Celonova Biosciences, Inc. Substrates containing polyphosphazene as matrices and substrates containing polyphosphazene with a micro-structured surface
ES2178961B1 (en) * 2001-03-06 2004-07-01 Instituto Cientifico Y Tecnologico De Navarra, S.A. MANUFACTURE OF NANOPARTICULES BASED ON THE COPYLIMER OF METHYL VINYL ETER AND MALEIC ANHYDRIDE FOR THE ADMINISTRATION OF PHARMACES OF HYDROPHYLICAL NATURE, IN PARTICULAR OF PURIC BASES AND PYRIMIDINICS.
WO2003005952A2 (en) * 2001-07-10 2003-01-23 Corixa Corporation Compositions and methods for delivery of proteins and adjuvants encapsulated in microspheres
CA2457018C (en) 2001-08-17 2010-12-14 Polyzenix Gmbh Device based on nitinol, a process for its production and its use
WO2003046054A2 (en) * 2001-11-29 2003-06-05 Parallel Solutions, Inc. Copolymer libraries and production and use thereof
US8088388B2 (en) * 2002-02-14 2012-01-03 United Biomedical, Inc. Stabilized synthetic immunogen delivery system
EP1894591B1 (en) 2002-03-20 2013-06-26 MannKind Corporation Cartridge for an inhalation apparatus
AU2003222137A1 (en) * 2002-03-29 2003-10-13 The Regents Of The University Of California Microgel particles for the delivery of bioactive materials
DE10224352A1 (en) * 2002-06-01 2003-12-11 Mueller Schulte Detlef Thermosensitive polymer carrier with changeable physical structure for biochemical analysis, diagnostics and therapy
US20080226723A1 (en) * 2002-07-05 2008-09-18 Celonova Biosciences, Inc. Loadable Polymeric Particles for Therapeutic Use in Erectile Dysfunction and Methods of Preparing and Using the Same
AU2003269904A1 (en) * 2002-07-10 2004-01-23 The Ohio State University Research Foundation Antigen-polymer compositions
US20040161470A1 (en) * 2002-11-22 2004-08-19 Alexander Andrianov Preparation of polyphosphazene microspheres
US20040131631A1 (en) * 2002-11-22 2004-07-08 Alexander Andrianov Polyphosphazene immunostimulants
ITMI20031617A1 (en) * 2003-08-06 2005-02-07 Fond Carlo E Dirce Callerio Onlus MICROCAPSULE WITH DOUBLE LAYER OF USE POLISACCHARIDES
US7338171B2 (en) * 2003-10-27 2008-03-04 Jen-Chuen Hsieh Method and apparatus for visual drive control
CN101027082A (en) * 2004-01-12 2007-08-29 曼恩坎德公司 Method of reducing serum proinsulin levels in type 2 diabetics
ATE449161T1 (en) * 2004-03-04 2009-12-15 Leukocare Ag LEUKOCYTE STIMULATION MATRIX
US20080090753A1 (en) 2004-03-12 2008-04-17 Biodel, Inc. Rapid Acting Injectable Insulin Compositions
US20080248999A1 (en) * 2007-04-04 2008-10-09 Biodel Inc. Amylin formulations
US7074256B2 (en) * 2004-05-13 2006-07-11 Battelle Energy Alliance, Llc Phosphazene membranes for gas separations
CN101010305B (en) 2004-08-20 2010-08-11 曼金德公司 Catalysis of diketopiperazine synthesis
PL2322180T3 (en) 2004-08-23 2015-10-30 Mannkind Corp Diketopiperazine salts for drug delivery
US20070292523A1 (en) * 2004-09-27 2007-12-20 Joey Moodley Dihydropyrimidine Formulations
KR101153785B1 (en) * 2004-10-25 2012-07-09 셀로노바 바이오사이언시스 저머니 게엠베하 Loadable polymeric particles for therapeutic and/or diagnostic applications and methods of preparing and using the same
US9114162B2 (en) 2004-10-25 2015-08-25 Celonova Biosciences, Inc. Loadable polymeric particles for enhanced imaging in clinical applications and methods of preparing and using the same
US9107850B2 (en) 2004-10-25 2015-08-18 Celonova Biosciences, Inc. Color-coded and sized loadable polymeric particles for therapeutic and/or diagnostic applications and methods of preparing and using the same
US20210299056A9 (en) 2004-10-25 2021-09-30 Varian Medical Systems, Inc. Color-Coded Polymeric Particles of Predetermined Size for Therapeutic and/or Diagnostic Applications and Related Methods
US20060193820A1 (en) 2005-02-18 2006-08-31 Andrianov Alexander K Immunostimulating polyphosphazene compounds
US8741454B2 (en) * 2005-03-29 2014-06-03 Toyota Motor Engineering & Manufacturing North America, Inc. Proton exchange membrane for fuel cell
CN104324362B (en) 2005-09-14 2018-04-24 曼金德公司 Method for preparation of drug based on improving affinity of the active agent to crystalline microparticle surfaces
US20070086952A1 (en) * 2005-09-29 2007-04-19 Biodel, Inc. Rapid Acting and Prolonged Acting Inhalable Insulin Preparations
US7713929B2 (en) 2006-04-12 2010-05-11 Biodel Inc. Rapid acting and long acting insulin combination formulations
US8084420B2 (en) 2005-09-29 2011-12-27 Biodel Inc. Rapid acting and long acting insulin combination formulations
KR100784485B1 (en) * 2006-01-18 2007-12-11 한국과학기술연구원 Biodegradable and thermosensitive polyorganophosphazene hydrogel, preparation method thereof and use thereof
CN104383546B (en) 2006-02-22 2021-03-02 曼金德公司 Method for improving the pharmaceutical properties of microparticles comprising diketopiperazines and an active agent
WO2007098607A1 (en) 2006-03-03 2007-09-07 Amorfix Life Sciences Ltd. Methods and compositions to treat and detect misfolded-sod1 mediated diseases
AU2007238114B2 (en) 2006-04-12 2010-10-14 Biodel, Inc. Rapid acting and long acting insulin combination formulations
CA2690539C (en) 2006-10-10 2014-10-07 Celonova Biosciences, Inc. Bioprosthetic heart valve with polyphosphazene
JP2010528893A (en) * 2007-05-18 2010-08-26 ハイアー ディメンション マテリアルズ，インコーポレイティド Flame-retardant and heat-insulating flexible material provided with an expansion protection plate, and method for producing the same
US20090016935A1 (en) * 2007-07-09 2009-01-15 Andrianov Alexander K Coating formulations including polyphosphazene polyelectrolytes and biologically active agents and asperities coated with such formulations
AU2008275743A1 (en) * 2007-07-09 2009-01-15 Apogee Technology, Inc. Immunostimulating polyphosphazene compounds for intradermal immunization
JP5501969B2 (en) 2007-09-11 2014-05-28 ユニバーシティ オブ グェルフ Polysaccharide immunogens derived from Clostridium difficile
KR101679812B1 (en) 2007-09-14 2016-11-28 사노피 파스테르 바이오로직스, 엘엘씨 Pharmaceutical compositions containing clostridium difficile toxoids a and b
WO2011163272A1 (en) 2010-06-21 2011-12-29 Mannkind Corporation Dry powder drug delivery system and methods
US20090110738A1 (en) * 2007-10-26 2009-04-30 Celonova Biosciences, Inc. Loadable Polymeric Particles for Cosmetic and Reconstructive Tissue Augmentation Applications and Methods of Preparing and Using the Same
US20090111763A1 (en) * 2007-10-26 2009-04-30 Celonova Biosciences, Inc. Loadable polymeric particles for bone augmentation and methods of preparing and using the same
CA2703947C (en) 2007-10-26 2018-12-04 Governing Council Of The University Of Toronto Therapeutic and diagnostic methods using tim-3
US20090110730A1 (en) * 2007-10-30 2009-04-30 Celonova Biosciences, Inc. Loadable Polymeric Particles for Marking or Masking Individuals and Methods of Preparing and Using the Same
US20090110731A1 (en) * 2007-10-30 2009-04-30 Celonova Biosciences, Inc. Loadable Polymeric Microparticles for Therapeutic Use in Alopecia and Methods of Preparing and Using the Same
US8485180B2 (en) 2008-06-13 2013-07-16 Mannkind Corporation Dry powder drug delivery system
DK2293833T3 (en) 2008-06-13 2016-05-23 Mannkind Corp DRY POWDER INHALER AND MEDICINAL ADMINISTRATION SYSTEM
KR101628410B1 (en) 2008-06-20 2016-06-08 맨카인드 코포레이션 An interactive apparatus and method for real-time profiling of inhalation efforts
TWI494123B (en) 2008-08-11 2015-08-01 Mannkind Corp Use of ultrarapid acting insulin
NZ601345A (en) 2008-10-16 2014-05-30 Univ Dalhousie Combination adjuvant formulation
US8314106B2 (en) 2008-12-29 2012-11-20 Mannkind Corporation Substituted diketopiperazine analogs for use as drug delivery agents
US9060927B2 (en) 2009-03-03 2015-06-23 Biodel Inc. Insulin formulations for rapid uptake
DK2405963T3 (en) 2009-03-11 2013-12-16 Mannkind Corp DEVICE, SYSTEM AND PROCEDURE FOR MEASURING RESISTANCE IN AN INHALATOR
WO2010123971A2 (en) * 2009-04-22 2010-10-28 Board Of Regents, The University Of Texas System Hydrogels for combinatorial delivery of immune-modulating biomolecules
GB2483815B (en) 2009-05-18 2013-12-25 Sigmoid Pharma Ltd Composition comprising oil drops
BRPI1013154B1 (en) 2009-06-12 2020-04-07 Mannkind Corp MICROPARTICLES OF DICETOPIPERAZINE WITH SPECIFIC SURFACE AREAS DEFINED, DRY POWDER UNDERSTANDING THE REFERRED MICROPARTICLES, METHOD FOR FORMATION OF THE REFERENCESMICROPARTICLES AND THE FORMATION OF MICROPARTYSTEMS
JP5911799B2 (en) 2009-08-12 2016-04-27 シグモイド・ファーマ・リミテッドＳｉｇｍｏｉｄ Ｐｈａｒｍａ Ｌｉｍｉｔｅｄ Immunomodulatory composition comprising a polymer matrix and an oil phase
EP2496295A1 (en) 2009-11-03 2012-09-12 MannKind Corporation An apparatus and method for simulating inhalation efforts
JP2013509963A (en) 2009-11-09 2013-03-21 スポットライト テクノロジー パートナーズ エルエルシー Fragmented hydrogel
WO2011057131A1 (en) 2009-11-09 2011-05-12 Spotlight Technology Partners Llc Polysaccharide based hydrogels
US9252455B1 (en) * 2010-04-14 2016-02-02 Hrl Laboratories, Llc Lithium battery structures employing composite layers, and fabrication methods to produce composite layers
SG194034A1 (en) 2011-04-01 2013-11-29 Mannkind Corp Blister package for pharmaceutical cartridges
CN102219911B (en) * 2011-04-28 2012-10-17 北京化工大学 Injectable polyphosphazene/gelatin composite hydrogel and preparation method thereof
WO2012174472A1 (en) 2011-06-17 2012-12-20 Mannkind Corporation High capacity diketopiperazine microparticles
AU2012328885B2 (en) 2011-10-24 2017-08-31 Mannkind Corporation Methods and compositions for treating pain
EP3536340A1 (en) * 2012-01-20 2019-09-11 Fernando Thome Kreutz Autologous cancer cell vaccine
BR112014018732A8 (en) 2012-02-01 2017-07-11 Univ Arizona IMMUNOGENIC COMPOSITIONS AGAINST CAMPYLOBACTER AND USES THEREOF
US9597385B2 (en) 2012-04-23 2017-03-21 Allertein Therapeutics, Llc Nanoparticles for treatment of allergy
GB201212010D0 (en) 2012-07-05 2012-08-22 Sigmoid Pharma Ltd Formulations
CN108057154B (en) 2012-07-12 2021-04-16 曼金德公司 Dry powder drug delivery system and method
CN103110941B (en) * 2012-10-09 2014-09-03 江苏康为世纪生物科技有限公司 Novel immunological adjuvant and quick immunization scheme
WO2014066856A1 (en) 2012-10-26 2014-05-01 Mannkind Corporation Inhalable influenza vaccine compositions and methods
ES2928365T3 (en) 2013-03-15 2022-11-17 Mannkind Corp Microcrystalline diketopiperazine compositions, methods of preparation and use thereof
EP3021834A1 (en) 2013-07-18 2016-05-25 MannKind Corporation Heat-stable dry powder pharmaceutical compositions and methods
CN105517607A (en) 2013-08-05 2016-04-20 曼金德公司 Insufflation apparatus and methods
GB201319791D0 (en) 2013-11-08 2013-12-25 Sigmoid Pharma Ltd Formulations
US10307464B2 (en) 2014-03-28 2019-06-04 Mannkind Corporation Use of ultrarapid acting insulin
US10561806B2 (en) 2014-10-02 2020-02-18 Mannkind Corporation Mouthpiece cover for an inhaler
HUE053624T2 (en) 2014-11-07 2021-07-28 Sublimity Therapeutics Ltd Compositions comprising cyclosporin
KR101762003B1 (en) 2015-07-16 2017-07-26 연세대학교 산학협력단 Delivery carrier of oral virus vaccine
WO2017079833A1 (en) 2015-11-09 2017-05-18 The University Of British Columbia Epitopes in amyloid beta mid-region and conformationally-selective antibodies thereto
EP3377560A4 (en) * 2015-11-18 2019-07-17 University of Maryland, College Park Polyphosphazenes, methods of making, and uses thereof
WO2018009672A1 (en) * 2016-07-06 2018-01-11 University Of Maryland, College Park Polyphosphazene polyelectrolytes and uses thereof
US20180125920A1 (en) * 2016-11-09 2018-05-10 The University Of British Columbia Methods for preventing and treating A-beta oligomer-associated and/or -induced diseases and conditions
EP3764991A4 (en) * 2018-03-13 2022-12-07 Capsular Technologies Pty Ltd. Vaccine composition
US11939429B1 (en) * 2018-06-29 2024-03-26 Hrl Laboratories, Llc Infrared-transparent polymers and methods of making and using the same
CN113271966A (en) * 2019-01-10 2021-08-17 首尔大学校产学协力团 Oral vaccine composition comprising hydrogel-encapsulated inactivated cells
IT201900007060A1 (en) 2019-05-21 2020-11-21 St Superiore Di Sanita Engineered tumor cells and their uses
US20200383932A1 (en) * 2019-06-05 2020-12-10 The Florida International University Board Of Trustees Biotherapy for viral infections using biopolymer based micro/nanogels
IT201900012540A1 (en) 2019-07-22 2021-01-22 Humanitas Mirasole Spa CHI3L1 inhibitors and their uses

Family Cites Families (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3893980A (en) * 1974-03-29 1975-07-08 Pennsylvania Res Corp Poly(amino acid alkyl ester phosphazenes)
FR2321896A1 (en) * 1975-08-29 1977-03-25 Anvar ACTIVE IMMUNOLOGICAL ADJUSTING AGENTS IN AQUEOUS SOLUTION
US4055520A (en) * 1976-07-14 1977-10-25 Armstrong Cork Company Polyphosphazene blends
US4026839A (en) * 1976-08-30 1977-05-31 Armstrong Cork Company Polyphosphazene polymer/silicone rubber blends and foams therefrom
US4209014A (en) * 1977-12-12 1980-06-24 Canadian Patents And Development Limited Dispensing device for medicaments
US4353888A (en) * 1980-12-23 1982-10-12 Sefton Michael V Encapsulation of live animal cells
US4495174A (en) * 1982-06-21 1985-01-22 Research Corporation Anesthetic polyorganophosphazenes
US4440921A (en) * 1982-06-21 1984-04-03 Research Corporation Coupling of polyorganophosphazenes to carboxylic acid
US4636387A (en) * 1982-06-21 1987-01-13 Research Corporation Anesthetic polyorganophosphazenes
US4451647A (en) * 1982-06-21 1984-05-29 Research Corporation Heparinized polyorganophosphazenes
US4639366A (en) * 1984-06-06 1987-01-27 Merck & Co., Inc. Polymers containing pendant acid functionalities and labile backbone bonds
US4880622A (en) * 1986-05-20 1989-11-14 Research Corporation Technologies, Inc. Water-soluble phosphazene polymers having pharmacological applications
NZ221306A (en) * 1986-08-15 1990-02-26 Commw Scient Ind Res Org 2-component immunoadjuvant comprising a mycobacterial free immunoadjuvant oil and a polycationic polyelectrolyte immunoadjuvant and vaccines thereof
US5075109A (en) * 1986-10-24 1991-12-24 Southern Research Institute Method of potentiating an immune response
GB8826116D0 (en) * 1988-11-08 1988-12-14 Danbiosyst Ltd Adhesive drug delivery composition
US4975280A (en) * 1989-01-23 1990-12-04 Ethyl Corporation Bioerodable sustained release implants
US4946938A (en) * 1989-08-01 1990-08-07 The University Of Pittsburgh A process for the catalytic synthesis of polyphosphazenes
US5104947A (en) * 1989-08-07 1992-04-14 Ethyl Corporation Polyphosphazenes and their synthesis
US5053451A (en) * 1990-01-19 1991-10-01 The Pennsylvania Research Corporation Ionically cross-linkable polyphosphazene: poly(bis(carboxylatophenoxy) phosphazene) and its hydrogels and membranes
US5126147A (en) * 1990-02-08 1992-06-30 Biosearch, Inc. Sustained release dosage form
US5149543A (en) * 1990-10-05 1992-09-22 Massachusetts Institute Of Technology Ionically cross-linked polymeric microcapsules
EP0539571A4 (en) * 1991-05-14 1993-12-15 Blue Sky Research, Inc. Dynamic shearing interferometer

Also Published As

Publication number Publication date
US5562909A (en) 1996-10-08
JPH09500629A (en) 1997-01-21
DK0710117T3 (en) 2002-02-18
ATE207505T1 (en) 2001-11-15
US5529777A (en) 1996-06-25
AU691824B2 (en) 1998-05-28
EP0710117A1 (en) 1996-05-08
DE69428795T2 (en) 2002-06-13
CN1134265C (en) 2004-01-14
EP0710117A4 (en) 1996-08-07
EP0710117B1 (en) 2001-10-24
KR960703620A (en) 1996-08-31
AU7326194A (en) 1995-02-13
BR9407051A (en) 1996-08-13
US5494673A (en) 1996-02-27
SG46659A1 (en) 1998-02-20
KR100352336B1 (en) 2003-04-16
PT710117E (en) 2002-04-29
NZ269396A (en) 1999-09-29
WO1995002628A1 (en) 1995-01-26
WO1995002415A1 (en) 1995-01-26
ES2166376T3 (en) 2002-04-16
KR960703617A (en) 1996-08-31
KR100353496B1 (en) 2003-03-03
DE69428795D1 (en) 2001-11-29
CA2166208C (en) 2010-04-20
CN1128954A (en) 1996-08-14

Similar Documents

Publication Publication Date Title
CA2166208A1 (en) Phosphazene polyelectrolytes as immunoadjuvants
US5855895A (en) Polyphosphazene polyelectrolyte immunoadjuvants
US8716217B2 (en) Polyglutamic acids functionalized by cationic groups and hydrophobic groups and applications thereof, in particular therapeutic applications thereof
US9687546B2 (en) Immunostimulating polyphosphazene compounds
KR920006912B1 (en) Water soluble high molecular polymerized pharmacentical preparation
ES2269694T3 (en) BLOCK COPOLYMER LOADED AFFILILE NEGATIVELY AS A VEHICLE FOR PHARMACES AND THE SAME COMPLEX WITH POSITIVELY LOADED PHARMACO.
US4863735A (en) Biodegradable polymeric drug delivery system with adjuvant activity
Ullah et al. Synthesis of polyphosphazenes with different side groups and various tactics for drug delivery
CA2145502A1 (en) Alginate-bioactive agent conjugates
CA2167081A1 (en) Hydrogel microencapsulated vaccines
CA2489010A1 (en) Bisacyloxypropylcysteine conjugates and their use
JPH0832781B2 (en) Biodegradable polymers for depot formulations and process for their preparation
CN105611936B (en) Immunopotentiating agent
WO2001015727A2 (en) Compositions of immunostimulatory polymers and saponin adjuvants and uses thereof
KR20170123767A (en) Method of Preparing Polygammaglutamic Acid-Chitosan Nanoparticles
AU738698B2 (en) Polyphosphazene polyelectrolyte immunoadjuvants
Andrianov Polyphosphazenes as vaccine adjuvants
EP1578441A2 (en) Polyphosphazene immunocstimulants
US20170258900A1 (en) Immunostimulating Polyphosphazene Compounds
Janovska et al. CHITOSAN NANOPARTICLES AS DELIVERY SYSTEM FOR NASAL IMMUNISATION.
Frère et al. Peptide Nanostructured Conjugates for Therapeutics: The Example of P140 Peptide for the Treatment of Systemic Lupus Erythematosus
CA1297627C (en) Biologically degradable polymers for depot preparations havingcontrolled release of the active compound
Vyas et al. 25 Chitosan/Chitosan Derivatives as Carriers and Immunoadjuvants in Vaccine Delivery

Legal Events

Date Code Title Description
EEER Examination request
MKLA Lapsed

Effective date: 20140708