Control of antibody responses to synthetic nanocarriers

a synthetic nanocarrier and antibody technology, applied in the field of synthetic nanocarrier compositions, can solve the problem that prior studies have not addressed the design of synthetic nanocarriers relative to optimizing humoral immune responses

Inactive Publication Date: 2013-02-14
SELECTA BIOSCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0022]In one embodiment, the composition further comprises one or more adjuvants.
[0023]In another embodiment, the composition further comprises one or more pharmaceutically acceptable excipients.

Problems solved by technology

The anti-carrier response is often of concern as it is not the intended effect of the vaccine and it may relate to undesirable side effects.
Prior studies have not addressed the design of synthetic nanocarriers relative to optimizing humoral immune responses.

Method used

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  • Control of antibody responses to synthetic nanocarriers
  • Control of antibody responses to synthetic nanocarriers
  • Control of antibody responses to synthetic nanocarriers

Examples

Experimental program
Comparison scheme
Effect test

example 1

Formulations of Synthetic Nanocarriers

Materials for Lot #1

[0165]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 approximately 4100 Da molecular weight having 5.2% w / w R848 content was synthesized by conjugation of R848 to the terminal-acid of commercially-supplied PLGA via an amide linkage. PLA-PEG-Nicotine with a nicotine-terminated PEG block of 3,500 Da and DL-PLA block of approximately 15,000 Da was synthesized. Polyvinyl alcohol (Mw=9,000-10,000, 80% hydrolyzed) was purchased from SIGMA (Part Number 360627).

Methods for Lot #1

[0166]Solutions were prepared as follows:

[0167]Solution 1: Ovalbumin peptide 323-339 amide acetate salt @ 70 mg / mL was prepared by dissolution in 0.13N hydrochloric acid at room temperature.

[0168]Solution 2: PLGA-R848 @ 75 mg / mL and PLA-PEG-Nicotine @ 25 mg / mL in dichloromethane was prepared...

example 2

Synthetic Nanocarriers with Increased Antigen Increases Antigen-Specific Antibody Generation and Decreases Anti-Carrier Antibody Generation

[0193]Mice were inoculated with nicotine-presenting R848-adjuvanted nanocarrier formulations. Groups 2 through 4 were evaluated for antigen-presentation and anti-carrier effect. The nicotine-presenting conjugate in the nanocarrier is a PLA-PEG3.5k-Nicotine construct of ˜15,350 Mw PLA and ˜3500 Mw PEG. The study groups used formulations having varied content of the PLA-PEG3.5k-Nicotine construct, partially-substituting the construct with either a ˜20 k Mw PLA polymer or with a PLA-PEG2k-OMe polymer of ˜18,700 Mw PLA and 2000 Mw PEG. Mice were immunized at days 0, 14, and 28 and serum was collected at days 26 and 40. The formulations are described as tabulated below and the anti-nicotine and resultant anti-PEG antibodies at day 40 are presented in FIG. 1.

TABLE 6Synthetic Nanocarrier Formulationsμg R848 / mgNP releasedPLGA-R848Polymer-AgReplacementR84...

example 3

Synthetic Nanocarriers with Increased Antigen or Increased Polymer Length Decreases Anti-Carrier Antibody Generation

[0196]Mice were inoculated with nicotine-presenting R848-adjuvanted nanocarrier formulations. All formulations were prepared on the same date using a consistent set of solutions and materials. All tested nanocarriers were formulated with a 50% PLGA-R848 polymer content, with the remaining 50% of the composition made up of one or more of the following polymers: PLA-PEG5k-Nicotine, PLA-PEG2k-OMe, PLA-PEG5k-OMe, or PLA.

TABLE 7Synthetic Nanocarrier FormulationsPLA-PEG-PLA-PEG2k-PLA-PEG5k-Ova PeptideR848NicOMeOMePLALoad (%LoadGr.NC Lot #(% w / w)(% w / w)(% w / w)(% w / w)w / w)(% w / w)142500252.04.12537.50012.51.84.436500001.03.9472525001.13.95837.512.5001.04.46937.5012.500.74.17102502500.14.08110050004.6912000500.74.2

[0197]Following a prime and two-boost inoculation schedule, the on-target (anti-nicotine) antibody titers and off-target (anti-PEG) antibody titers were determined by E...

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Abstract

Disclosed are synthetic nanocarrier compositions that comprise B cell antigen for desired antibody production and an off-target response attenuating polymeric coating as well as related methods.

Description

RELATED APPLICATIONS[0001]This application claims the benefit under 35 U.S.C. §119 of U.S. provisional application 61 / 513,496, 61 / 513,526 and 61 / 513,527, each filed Jul. 29, 2011, the entire contents of each of which are incorporated herein by reference.FIELD OF THE INVENTION[0002]This invention relates to synthetic nanocarrier compositions that comprise an off-target response attenuating polymeric coating, and related methods, such as for treating diseases or conditions in which generating an immune response against a B cell antigen is desirable.BACKGROUND OF THE INVENTION[0003]Anti-carrier antibody generation by a nanocarrier vaccine is an off-target side effect that may have direct unintended or undesirable impacts on pharmaceutical or biomedical formulations of related compositions, and may interfere with the generation of desired anti-B cell antigen antibodies. Therefore, improved compositions and therapeutic methods to avoid or minimize undesirable anti-carrier effects are nee...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K9/00A61P37/04A61K39/385B82Y5/00
CPCA61K39/385A61K39/39A61K2039/55555Y10T428/2982A61K47/482A61K47/48315A61K47/48192A61K47/59A61K47/593A61K47/645A61P31/00A61P31/12A61P31/14A61P31/16A61P31/18A61P31/20A61P33/02A61P33/06A61P35/00A61P37/02A61P37/04Y02A50/30A61K47/50A61K9/16A61K47/30
Inventor PITTET, LYNNELLE ANN MCNAMEEALTREUTER, DAVID H.GAO, YUNILYINSKII, PETRKUHLMAN, WILLIAM
Owner SELECTA BIOSCI
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