IP Library Granted Patent US 9,920,128
Granted Patent B2
US 9,920,128 · App. 15/001,349 · Granted Mar 20, 2018

Synthetic antiserum for rapid-turnaround therapies

Inventors: Jeffrey S. Lin (Silver Spring, MD); Andrew B. Feldman (Columbia, MD); Jared D. Evans (Ellicott City, MD); Joshua T. Wolfe (Bethesda, MD); David Weitz (Bolton, MA); John Heyman (Somerville, MA); Andrew S. Pekosz (Towson, MD)
Assignee: The Johns Hopkins University
C07K16/30C07K16/00
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Quick Facts
Patent No.
US 9,920,128
App. No.
15/001,349
Granted
Mar 20, 2018
Kind
B2
Abstract

A method for synthesizing an antiserum for rapid-turnaround therapies includes collecting antibody-secreting cells from a test subject, wherein the test subject has been exposed to a target biological agent and has produced an antibody response; selecting a subset of the antibody-secreting cells, the subset of the antibody-secreting cells producing antibodies that neutralize the target biological agent; generating variable-region-coding DNA sequences from the antibodies that neutralize the target biological agent; tagging amplicons of the variable-region-coding DNA sequences with unique nucleic acid identifiers to associate the variable-region-coding DNA sequences derived from individual ones of the subset of the antibody-secreting cells; analyzing antibody-type distribution in a natural immune response; synthesizing antibodies from the variable-region-coding DNA sequences to form synthetic antibodies; and mixing the synthetic antibodies in a proportion equal to the antibody-type distribution in the natural immune response to form the antiserum.

Claims (22)

1. A method for synthesizing an antiserum for rapid-turnaround therapies, the method comprising:

collecting antibody-secreting cells from a test subject, wherein the test subject has been exposed to a target biological agent and has produced a successful antibody response;

selecting a subset of the antibody-secreting cells, the subset of the antibody-secreting cells producing antibodies that neutralize the target biological agent;

generating variable-region-coding DNA sequences from the antibodies that neutralize the target biological agent;

tagging amplicons of the variable-region-coding DNA sequences with unique nucleic acid identifiers to associate the variable-region-coding DNA sequences derived from individual ones of the subset of the antibody-secreting cells;

analyzing antibody-type distribution in a natural immune response;

synthesizing antibodies from the variable-region-coding DNA sequences to form synthetic antibodies; and

mixing the synthetic antibodies in a proportion equal to the antibody-type distribution in the natural immune response to form the antiserum.

2. The method according to claim 1 , wherein collecting the antibody-secreting cells from the test subject comprises:

extracting a sample containing white blood cells from blood or bone marrow of the test subject; and

isolating at least one of B cells or plasma cells from the sample.

3. The method according to claim 1 , wherein selecting the subset of the antibody-secreting cells comprises:

encapsulating each antibody-secreting cell in a droplet via droplet microfluidics;

screening each antibody-secreting cell for neutralization of the target biological agent via a binding assay within the droplet; and

selecting the subset of the antibody-secreting cells that neutralize the target biological agent.

4. The method according to claim 1 , further comprising an initial operation of priming the antibody response in the test subject.

5. The method according to claim 4 , wherein priming the antibody response in the test subject comprises vaccinating the test subject or selecting a previously infected test subject.

6. The method according to claim 5 , further comprising boosting the natural immune response in the test subject.

7. The method according to claim 4 , further comprising challenging the natural immune response in the test subject after priming the antibody response in the test subject and prior to collecting the antibody-secreting cells from the test subject.

8. The method according to claim 1 , further comprising validating neutralization properties of the antiserum after synthesis.

9. The method according to claim 1 , wherein the test subject comprises a human or a non-human animal.

10. The method according to claim 1 , wherein the target biological agent comprises at least one of a virus, a bacterium, a prion, a toxin, a cancer, or any combination thereof.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 30, 2016
From: FELDMAN, ANDREW B.; EVANS, JARED D.; WOLFE, JOSHUA T.
To: THE JOHNS HOPKINS UNIVERSITY
Reel/Frame 038139/0757 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 20, 2016
From: LIN, JEFFREY S.; PEKOSZ, ANDREW S.
To: THE JOHNS HOPKINS UNIVERSITY
Reel/Frame 037531/0009 →
Continuity (2)
Provisional Application 62108676 · Jan 28, 2015
Related Publication 20160215282A1 · Jul 28, 2016