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Nanocarrier compositions with uncoupled adjuvant

a technology of adjuvant and composition, applied in the direction of powder delivery, macromolecular non-active ingredients, inorganic non-active ingredients, etc., can solve the problem of not yet known optimal approach for augmenting the immune response with adjuvan

Inactive Publication Date: 2011-12-01
SELECTA BIOSCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0035]In other embodiments, the administration of adjuvant separate from synthetic nanocarriers leads to a rapid and strong systemic induction of cytokines that are important for a Th1 immune response, such as IFN-γ, IL-12 and / or IL-18. Therefore, the dose of the adjuvant or adjuvants in the compositions in some embodiments is a systemic dose that results in the systemic release of IFN-γ, IL-12 and / or IL-18. As such cytokines are important for a Th1 immune response, the administration of compositions provided herein can be beneficial to subjects where a Th1 immune response is desired. In some embodiments, the compositions provided are administered to such subjects. In embodiments, such subjects have or are at risk of having an atopic condition, asthma, chronic obstructive pulmonary disease (COPD) or a chronic infection. Methods for the administration of the compositions to such subjects are also provided.

Problems solved by technology

The optimal approach for augmenting the immune response with adjuvant, however, in a number of cases, is not yet known.

Method used

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  • Nanocarrier compositions with uncoupled adjuvant
  • Nanocarrier compositions with uncoupled adjuvant
  • Nanocarrier compositions with uncoupled adjuvant

Examples

Experimental program
Comparison scheme
Effect test

example 1

Administration of Nanocarrier and Admixed R848 Adjuvant Results in Strong Systemic Production of Inflammatory Cytokines

Materials for NC-R848-1 Nanocarrier Formulations

[0146]Ovalbumin peptide 323-339 amide acetate salt, was purchased from Bachem Americas Inc. (3132 Kashiwa Street, Torrance Calif. 90505. Part #4065609.) PLGA-R848 conjugate of 75 / 25 lactide / glycolide monomer composition and of approximately 4100 Da molecular weight having 5.2% w / w R848 content was synthesized. PLA-PEG-Nicotine with a nicotine-terminated PEG block of approximately 3,500 Da and DL-PLA block of approximately 15,000 Da was synthesized Polyvinyl alcohol (Mw=11,000-31,000, 87-89% hydrolyzed) was purchased from J.T. Baker (Part Number U232-08).

Methods for NC-R848-1 Nanocarrier Production

[0147]Solutions were prepared as follows:

[0148]Solution 1: Ovalbumin peptide 323-339 @ 70 mg / mL was prepared in 0.13N hydrochloric acid at room temperature.

[0149]Solution 2: PLGA-R848 @ 75 mg / mL and PLA-PEG-Nicotine @ 25 mg / mL...

example 2

Coupling of Nanocarrier to R848 Adjuvant does not Inhibit Systemic Production of Immune Cytokine IFN-γ

Materials for NC-R848 Nanocarrier Formulations

[0168]Ovalbumin peptide 323-339 amide acetate salt was purchased from Bachem Americas Inc. (3132 Kashiwa Street, Torrance Calif. 90505. Part #4065609.) PLGA-R848 conjugate of 75 / 25 lactide / glycolide monomer composition and of approximately 4100 Da molecular weight having 5.2% w / w R848 content was synthesized. PLA-PEG-Nicotine with a nicotine-terminated PEG block of approximately 3,500 Da and DL-PLA block of approximately 15,000 Da was synthesized. Polyvinyl alcohol (Mw=11,000-31,000, 87-89% hydrolyzed) purchased from J.T. Baker (Part Number U232-08).

Methods for NC-R848 Nanocarrier Production

[0169]Solutions were prepared as follows:

[0170]Solution 1: Ovalbumin peptide 323-339 @ 70 mg / mL was prepared in 0.13N hydrochloric acid at room temperature.

[0171]Solution 2: PLGA-R848 @ 75 mg / mL and PLA-PEG-Nicotine @ 25 mg / mL in dichloromethane was p...

example 3

Addition of Free Adjuvant Augments Immune Response

Materials for NC-Nic w / o R848 Nanocarrier Formulations

[0183]Ovalbumin peptide 323-339 amide TFA salt was purchased from Bachem Americas Inc. (3132 Kashiwa Street, Torrance Calif. 90505. Part #4064565.) PLA with an inherent viscosity of 0.19 dL / g was purchased from Boehringer Ingelheim (Ingelheim Germany. Product Code R202H). PLA-PEG-Nicotine with a nicotine-terminated PEG block of approximately 3,500 Da and DL-PLA block of approximately 15,000 Da was synthesized. Polyvinyl alcohol (Mw=11,000-31,000, 87-89% hydrolyzed) was purchased from J.T. Baker (Part Number U232-08).

Methods for NC-Nic w / o R848 Nanocarrier Production

[0184]Solutions were prepared as follows:

[0185]Solution 1: Ovalbumin peptide 323-339 @ 69 mg / mL was prepared in 0.13N hydrochloric acid at room temperature.

[0186]Solution 2: PLA @ 75 mg / mL and PLA-PEG-Nicotine @ 25 mg / mL in dichloromethane was prepared by dissolving PLA @ 100 mg / mL in dichloromethane and PLA-PEG-Nicotin...

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Abstract

Disclosed are synthetic nanocarrier compositions with separate adjuvant compositions as well as related methods.

Description

RELATED APPLICATIONS[0001]This application claims the benefit under 35 U.S.C. §119 of U.S. provisional applications 61 / 348,713, filed May 26, 2010, 61 / 348,717, filed May 26, 2010, 61 / 348,728, filed May 26, 2010, and 61 / 358,635, filed Jun. 25, 2010, the entire contents of each of which are incorporated herein by reference.FIELD OF THE INVENTION[0002]This invention relates to synthetic nanocarrier and separate adjuvant compositions, and related methods, such as for treating diseases in which generating an immune response is desirable.BACKGROUND OF THE INVENTION[0003]Adjuvants are generally important components for the majority of currently used vaccination regimens. The optimal approach for augmenting the immune response with adjuvant, however, in a number of cases, is not yet known. Therefore, improved compositions and therapeutic methods are needed to provide improved therapies for diseases in which generating an immune response and / or augmenting it is desirable.SUMMARY OF THE INVEN...

Claims

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Application Information

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IPC IPC(8): A61K9/127A61K47/30A61K47/42A61K39/385A61P29/00A61K9/14A61P35/00A61P31/00A61P17/00A61P11/06A61P11/00A61K39/00A61P37/00
CPCA61K9/5153A61K2039/55522A61K31/7115A61K33/06A61K39/0013A61K39/385A61K39/39A61K45/06A61K47/02A61K47/22A61K47/24A61K47/48176A61K47/482A61K47/48215A61K47/48853A61K2039/555A61K2039/55511A61K2039/55555A61K2039/6093A61K31/4745A61K2300/00A61K47/34A61K39/12C12N2730/10134C12N2760/16134A61K2039/6031A61K2039/60A61K2039/55561A61K2039/70A61K2039/6087A61K47/60A61K47/58A61K47/593A61K47/6921A61P1/16A61P11/00A61P11/06A61P11/08A61P17/00A61P17/04A61P25/28A61P25/30A61P25/34A61P25/36A61P29/00A61P3/00A61P31/00A61P31/04A61P31/10A61P31/12A61P31/14A61P31/16A61P31/20A61P31/22A61P35/00A61P37/00A61P37/02A61P37/04A61P37/08A61P39/02A61P43/00A61P5/00Y02A50/30A61K39/395A61K38/17A61K9/0012A61K39/0005A61K39/35A61K2039/54A61K2039/541A61K2039/542A61K2039/543A61K47/6931A61K47/68A61K47/646A61K47/6929
Inventor BRATZLER, ROBERT L.JOHNSTON, LLOYDLIPFORD, GRAYSON B.ZEPP, CHARLES
Owner SELECTA BIOSCI
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