Granted Patent
B2
US 12,222,349 · App. 17/216,514 · Granted Feb 11, 2025
Compositions, methods and systems for protein corona analysis and uses thereof
Inventors:
Hongwei Xia (Fremont, CA); Lyndal Hesterberg (Loveland, CO); Michael Figa (San Mateo, CA); Xiaoyan Zhao (Foster City, CA); Gregory Troiano (Pembroke, MA); William Manning (Redwood City, CA); John Blume (Bellingham, WA); Omid Farokhzad (Waban, MA); Matthew McLean (Redwood City, CA); Craig Stolarczyk (San Mateo, CA); Marwin Ko (Redwood City, CA); Theodore Platt (Danville, CA)
Assignee:
Seer, Inc.
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Abstract
Compositions, methods, and systems for analyzing the protein corona are described herein, as well as its application in the discovery of advanced diagnostic tools as well as therapeutic targets.
Claims (49)
1. A kit for identifying proteins in a biological sample, comprising:
(a) a plurality of magnetic particles configured to bind a plurality of proteins in the biological sample when the plurality of magnetic particles is incubated with the biological sample, wherein the plurality of magnetic particles comprise a polymer, wherein the polymer comprises an ammonium functional group, wherein the polymer comprises a recurring unit of:
wherein the plurality of magnetic particles comprise a positive zeta potential, and wherein the positive zeta potential of the plurality of magnetic particles range from 10 mV to 60 mV;
(b) a reducing agent configured to reduce the plurality of proteins; and
(c) an enzymatic agent configured to digest the plurality of proteins.
2. The kit of claim 1 , wherein the polymer comprises poly(N-(3-(dimethylamino)propyl)methacrylamide) (PDMAPMA).
3. The kit of claim 2 , wherein the plurality of magnetic particles comprises iron oxide.
4. The kit of claim 3 , wherein the plurality of magnetic particles comprise a plurality of nanoparticles.
5. The kit of claim 4 , wherein a polydispersity index of the plurality of magnetic particles is less than 0.5.
6. The kit of claim 1 , further comprising an alkylating agent for alkylating the plurality of proteins.
7. The kit of claim 6 , further comprising an elution buffer for eluting digested proteins.
8. The kit of claim 1 , wherein the plurality of magnetic particles is configured to bind at least 200 unique proteins when incubated with the biological sample.
9. The kit of claim 1 , wherein the positive zeta potential of the plurality of magnetic particles range from 20 mV to 40 mV.
10. The kit of claim 1 , further comprising (d) a solid-phase for purifying a plurality of peptides using solid-phase extraction.
11. A kit for identifying proteins in a biological sample, comprising:
(a) a plurality of magnetic particles configured to bind a plurality of proteins in the biological sample when the plurality of magnetic particles is incubated with the biological sample, wherein the plurality of magnetic particles comprise a polymer, wherein the polymer comprises an ammonium functional group, wherein the ammonium functional group comprises a tertiary ammonium, wherein the plurality of magnetic particles comprise a positive zeta potential, and wherein the positive zeta potential of the plurality of magnetic particles range from 10 mV to 60 mV;
(b) a reducing agent configured to reduce the plurality of proteins; and
(c) an enzymatic agent configured to digest the plurality of proteins.
12. A kit for identifying proteins in a biological sample, comprising:
(a) a plurality of magnetic particles configured to bind a plurality of proteins in the biological sample when the plurality of magnetic particles is incubated with the biological sample, wherein the plurality of magnetic particles comprise a polymer, wherein the polymer comprises an ammonium functional group, wherein the ammonium functional group comprises a quaternary ammonium, wherein the plurality of magnetic particles comprise a positive zeta potential, and wherein the positive zeta potential of the plurality of magnetic particles range from 10 mV to 60 mV;
(b) a reducing agent configured to reduce the plurality of proteins; and
(c) an enzymatic agent configured to digest the plurality of proteins.
13. The kit of claim 1 , wherein the plurality of magnetic particles comprises a plurality of microparticles.
14. The kit of claim 1 , wherein the polymer is cross-linked.
15. A kit for identifying proteins in a biological sample, comprising:
(a) a plurality of magnetic particles configured to bind a plurality of proteins in the biological sample when the plurality of magnetic particles is incubated with the biological sample, wherein the plurality of magnetic particles comprise a polymer, wherein the polymer comprises divinylbenzene, and wherein the plurality of magnetic particles comprise a positive zeta potential;
(b) a reducing agent configured to reduce the plurality of proteins; and
(c) an enzymatic agent configured to digest the plurality of proteins.
16. The kit of claim 1 , further comprising (d) a buffer configured to maintain acidic pH conditions when the plurality of magnetic particles is incubated with the biological sample.
17. The kit of claim 8 , wherein the plurality of magnetic particles is configured to bind to at least 400 unique proteins when incubated with the biological sample.
18. The kit of claim 1 , wherein the plurality of magnetic particles are porous.
19. The kit of claim 11 , wherein the plurality of magnetic particles comprises iron oxide.
20. The kit of claim 19 , wherein the plurality of magnetic particles comprise a plurality of nanoparticles.
21. The kit of claim 11 , wherein the plurality of magnetic particles is configured to bind at least 200 unique proteins when incubated with the biological sample.
22. The kit of claim 11 , further comprising (d) a solid-phase for purifying a plurality of peptides using solid-phase extraction.
23. The kit of claim 11 , wherein the plurality of magnetic particles comprises a plurality of microparticles.
24. The kit of claim 11 , wherein the polymer is cross-linked.
25. The kit of claim 12 , wherein the plurality of magnetic particles comprises iron oxide.
26. The kit of claim 25 , wherein the plurality of magnetic particles comprise a plurality of nanoparticles.
27. The kit of claim 12 , wherein the plurality of magnetic particles is configured to bind at least 200 unique proteins when incubated with the biological sample.
28. The kit of claim 12 , further comprising (d) a solid-phase for purifying a plurality of peptides using solid-phase extraction.
29. The kit of claim 12 , wherein the plurality of magnetic particles comprises a plurality of microparticles.
30. The kit of claim 12 , wherein the polymer is cross-linked.
31. The kit of claim 15 , wherein the plurality of magnetic particles comprises iron oxide.
32. The kit of claim 31 , wherein the plurality of magnetic particles comprise a plurality of nanoparticles.
33. The kit of claim 15 , wherein the plurality of magnetic particles is configured to bind at least 200 unique proteins when incubated with the biological sample.
34. The kit of claim 15 , further comprising (d) a solid-phase for purifying a plurality of peptides using solid-phase extraction.
35. The kit of claim 15 , wherein the plurality of magnetic particles comprises a plurality of microparticles.
36. The kit of claim 15 , wherein the polymer is cross-linked.
Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Jul 8, 2022
From: XIA, HONGWEI; HESTERBERG, LYNDAL; FIGA, MICHAEL; ZHAO, XIAOYAN; TROIANO, GREGORY; MANNING, WILLIAM; BLUME, JOHN; FAROKHZAD, OMID; MCLEAN, MATTHEW; STOLARCZYK, CRAIG; KO, MARWIN; PLATT, THEODORE
To: SEER, INC.
Reel/Frame 060460/0048 →
Continuity (5)
Continuation
PCTUS2019000061
· Nov 7, 2019
Provisional Application
62756960
· Nov 7, 2018
Provisional Application
62824278
· Mar 26, 2019
Provisional Application
62874862
· Jul 16, 2019
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