BIODEGRADABLE POLYMERIC PARTICLES ENCAPSULATING AN ACTIVE AGENT, PHARMACEUTICAL COMPOSITIONS AND USES THEREOF

• US 20180078507A1
• Filed: 09/15/2017
• Published: 03/22/2018
• Est. Priority Date: 09/16/2016
• Status: Active Grant

• Current Assignee: Altimmune, Inc., Auburn University
• Original Assignee: Altimmune, Inc., Auburn University
• Inventors: David, Allan E., Baker, Henry J., Johnson, Aime K., Roberts, M. Scot, Van Kampen, Kent R., Sangle, Prachi
• Granted Patent: US 11,395,802 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 2039/55555 Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers
• CPC Class Codes: A61K 39/12 Viral antigens
• CPC Class Codes: A61K 39/145 Orthomyxoviridae, e.g. influenza virus
• CPC Class Codes: A61K 39/235 Adenoviridae
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/0095 Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches A61K9/0007 takes precedence; eatable gels or foams A61K9/0056; oral mucosa adhesive forms A61K9/006
• CPC Class Codes: A61K 9/19 lyophilised , i.e. freeze-dried, solutions or dispersions lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00
• CPC Class Codes: A61K 9/5031 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poly(lactide-co-glycolide)
• CPC Class Codes: A61K 9/5036 Polysaccharides, e.g. gums, alginate; Cyclodextrin
• CPC Class Codes: A61K 9/5153 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61P 31/16 for influenza or rhinoviruses
• CPC Class Codes: A61P 31/20 for DNA viruses
• CPC Class Codes: C12N 2710/10034 Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• CPC Class Codes: C12N 2710/10343 viral genome or elements thereof as genetic vector
• CPC Class Codes: C12N 2760/16034 Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• CPC Class Codes: C12N 2760/16071 Demonstrated in vivo effect
• CPC Class Codes: C12N 2760/16134 Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein

Abstract

Therapeutic or prophylactic compositions providing an active agent, such as an antigen or a vector that contains and expresses an antigen, encapsulated in or incorporated into a biodegradable polymeric particle are provided. The compositions can also provide an active agent that is not encapsulated in or incorporated into the biodegradable polymeric particle in order to provide an initial or prime delivery of the active agent. Particles or composites providing an active agent encapsulated by a first and second polymer are also provided, wherein polymers are distributed in a gradient from a core of the composite to a surface of the composite, and configured to provide a delayed release of the active agent by a period of 7 days to 6 months. Methods of producing composites are also provided. Pharmaceutical formulations providing a single dose composition are also provided, along with methods for administering the pharmaceutical compositions to a subject in need thereof a therapeutically effective amount of an active agent are provided.

Claims

1-68. -68. (canceled)

69. :

A pharmaceutical composition comprising;

a) a biodegradable polymeric composite particle comprising;

at least one active agent encapsulated in a hollow or aqueous core by a shell comprising a mixture of a first polymer, wherein the first polymer is a hydrophobic polymer, and a second polymer, wherein the at least one active agent is released over a period of 7 days to 6 months; and

b) at least one active agent free from and not encapsulated by the polymeric composite particle;

wherein the at least one additional active agent provides an initial dose and the polymeric composite particle provides a delayed dose of the active agent, wherein the active agent encapsulated in the core and the active agent free from the particle can be the same active agent or different active agents.

70. :

The composition of claim 69, wherein the polymeric composite particle does not comprise alginate.

71. :

The composition of claim 69, wherein the polymeric composite particle does not comprise divalent or trivalent cations as cross-linking reagents.

72. :

The composition of claim 71, wherein the polymeric composite particle does not comprise divalent cations, selected from Ca²⁺, Sr²⁺, Zn²⁺, Co²⁺ or Ba²⁺, or trivalent cations Fe³⁺ or Al⁺.

73. :

The composition of claim 69, in a lyophilized for freeze-dried form.

74. :

The composition of claim 73, wherein the polymeric composite particle comprises between 1% and 10% water (w/v) at neutral pH, excluding the aqueous core.

75. :

The composition of claim 73, wherein the composition is reconstituted in an aqueous solution comprising a pharmaceutical acceptable excipient, diluent, or carrier.

76. :

The composition of claim 69, wherein the active agent is selected from a vaccine, a therapeutic agent, an immune mediator, a probiotic, a pharmaceutical, a vitamin, an adjuvant, or a cancer antigen.

77. :

The composition of claim 69, wherein the polymeric composite particles further comprise an enzyme or catalytic agent.

78. :

The composition of claim 69, wherein the second polymer is degraded via hydrolysis, enzymatic or catalytic activity, or a combination thereof.

79. :

The composition of claim 69, wherein the first polymer of the polymeric composite particle is poly (L-glycolic acid) (PLGA), polyglycolic acid (PGA), polylactic acid (PLA), poly(L-lactic acid) (PLLA), polyglycolide, poly-L-lactide, poly-D-lactide, poly(amino acids), polydioxanone, polycaprolactone, polygluconate, polylactic acid-polyethylene oxide copolymers, polyorthoesters, polyhydroxybutyrate, polyanhydride, polyphosphoester, poly(alpha-hydroxy acid), and the second polymer of the polymeric composite particle is chitosan, alginate, collagen, dextran, polyester, cellulose, carboxymethyl cellulose, modified cellulose, collagen, DNA, RNA or poly(amino acids).

80. :

A method for delivering an initial dose and a delayed dose in a single administration dose, comprising;

administering the pharmaceutical composition of claim 69 to an animal in need thereof.

81. :

The method of claim 80, further comprising reconstituting a lyophilized form of the pharmaceutical composition prior to administration.

82. :

The method of claim 80, wherein administration is selected from oral, intranasal, topical, intramuscular, mucosal, intravenous, or intraperitoneal.

83. :

The method of claim 80, wherein the animal is selected from a human, a horse, a dog, a cat, a pig, a cow, a sheep, a chicken, and a goat.

84. :

The method of claim 80, wherein the active agent is a vaccine to an infectious pathogen and the initial dose is a prime dose and the delayed dose is a boost dose.

85. :

The method of claim 84, wherein the delayed dose is delivered as a burst or bolus dose between 2 weeks and 6 months after administration of the pharmaceutical composition.

86. :

The method of claim 84, wherein the single administration dose induces and a rapid and prolonged immune response to the infectious pathogen.

87. :

The method of claim 86, wherein the infectious pathogen is a virus, bacterium, or fungus.

88. :

A biodegradable polymeric composite particle comprising;

at least one active agent encapsulated in core by a shell comprising a mixture of a first polymer, wherein the first polymer is a hydrophobic polymer, and a second polymer, wherein the shell is configured to provide a delayed release of the active agent(s) by a period of 7 days to 6 months.