IP Library Granted Patent US 9,334,367
Granted Patent B2
US 9,334,367 · App. 14/805,831 · Granted May 10, 2016

Carrier nanoparticles and related compositions, methods and systems

Inventors: Mark E. Davis (Pasadena, CA); Akinleye Alabi (Cambridge, MA)
Assignee: California Institute of Technology
C08G69/48A61K9/14A61K9/5146A61K31/337A61K31/4745A61K31/704A61K47/48092A61K47/48207A61K47/48907C08G59/4078
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 9,334,367
App. No.
14/805,831
Granted
May 10, 2016
Kind
B2
Abstract

Carrier nanoparticles comprising a polymer containing a polyol coupled to a polymer containing a boronic acid, configured to present the polymer containing a boronic acid to an environment external to the nanoparticle and related compositions, methods and systems.

Claims (50)

1. A nanoparticle comprising a polyol-containing polymer, a boronic acid-containing polymer, and at least one targeting ligand molecule;

wherein the boronic acid-containing polymer having a structure of formula:

wherein

R 3 and R 4 are independently (CH 2 CH 2 O) t , where t is from 2 to 2000,

X 1 is —NH—C(═O)—, —C(═O)—NH—CH 2 —, —C(═O)—NH—, —S—S—, —O—C(═O)— or —C(═O)—O—;

Y 1 is an alkylene with a carbon number of at least 1 or is an aromatic group;

Functional group 2 independently comprises —OCH 3 , —OH, —B(OH) 2 , —COOH, —NH 2 , or —(X 1 )—(Y 1 )—B(OH) 2 ;

r is 1;

a is 0; and

b is 1; and

said boronic acid-containing polymer being coupled to the polyol-containing polymer with reversible borate ester linkages formed between the —B(OH) 2 of the boronic acid-containing polymer and vicinal diols of the polyol-containing polymer;

said targeted nanoparticle being configured to present the boronic acid-containing polymer to an environment external to the nanoparticle; and

wherein the boronic acid-containing polymer is conjugated to the at least one targeting ligand molecule by coupling with the or Functional group 2.

2. The nanoparticle of claim 1 , wherein the polyol-containing polymer comprises mucic acid.

3. The nanoparticle of claim 1 , wherein the polyol-containing polymer further comprises polyethylene glycol linkages of formula:

where n is where n is from 1 to 20 at each occurrence.

4. The nanoparticle of claim 1 , wherein the polyol-containing polymer further comprises amidines groups, primary amine groups, secondary amine groups, tertiary amine groups, imidazolium groups, or protonated derivatives thereof.

5. The nanoparticle of claim 1 , wherein the polyol-containing polymer comprises mucic acid, polyethylene glycol linkages having 1 to 20 ethylene glycol moieties, and protonated amidine groups.

6. The nanoparticle of claim 1 , wherein Y 1 is phenyl.

7. The nanoparticle of claim 1 , wherein t is from 100 to 300.

8. The nanoparticle of claim 1 , wherein Functional group 2 independently comprises —COOH, —NH 2 , —OH, or —B(OH) 2 .

9. The nanoparticle of claim 1 wherein:

the polyol-containing polymer comprises mucic acid, polyethylene glycol linkages having 1 to 20 ethylene glycol moieties, and protonated amidine groups;

Y 1 is phenyl;

t is 20 to 300; and

Functional group 2 comprises —OH, —B(OH) 2 , —COOH, or —NH 2 .

10. The nanoparticle of claim 9 , wherein the nanoparticle is coupled to more than one targeting ligand molecules per nanoparticle.

11. The nanoparticle of claim 10 , wherein the targeting ligand molecule comprises an antibody, an antibody fragment, transferrin, folic acid, a ligand for a cellular receptor, a cellular receptor protein, an aptamer, or a fragment of an antibody, transferrin, a ligand for a cellular receptor, or a cellular receptor protein.

12. The nanoparticle of claim 10 , wherein the targeting ligand molecule comprises a small molecule, protein, protein fragment, peptide, full antibody, antibody fragment, monosaccharide, polysaccharide, nucleotide, or polynucleotide.

13. The nanoparticle of claim 10 , further comprising a therapeutic agent incorporated therein or coupled thereto.

14. The nanoparticle of claim 13 , wherein the therapeutic agent is a small molecule chemotherapeutic agent or a polynucleotide.

15. The nanoparticle of claim 13 , wherein the therapeutic agent is genomic DNA, cDNA, mRNA, siRNA, shRNA, miRNA, an antisense oligonucleotide, a viruses, or a chimeric polynucleotide.

16. The nanoparticle of claim 15 , wherein the therapeutic agent is an interfering RNA.

17. The nanoparticle of claim 13 , wherein the therapeutic agent comprises camptothecin, doxorubicin, or taxol.

18. An aqueous solution or dispersion of a plurality of nanoparticles of claim 10 .

19. The aqueous solution of dispersion of claim 18 , wherein each nanoparticle further comprises a therapeutic agent incorporated therein or coupled thereto.

20. The aqueous solution of dispersion of claim 19 , wherein therapeutic agent is a small molecule chemotherapeutic agent or a polynucleotide.

21. The aqueous solution of dispersion of claim 19 , wherein therapeutic agent is an interfering RNA.

22. The nanoparticle of claim 9 , wherein the nanoparticle is coupled to one targeting ligand molecule per nanoparticle.

23. The nanoparticle of claim 22 , wherein the targeting ligand molecule comprises an antibody, an antibody fragment, transferrin, folic acid, a ligand for a cellular receptor, a cellular receptor protein, an aptamer, or a fragment of an antibody, transferrin, a ligand for a cellular receptor, or a cellular receptor protein.

24. The nanoparticle of claim 22 , wherein the targeting ligand molecule comprises a small molecule, protein, protein fragment, peptide, full antibody, antibody fragment, monosaccharide, polysaccharide, nucleotide, or polynucleotide.

25. The nanoparticle of claim 22 , further comprising a therapeutic agent incorporated therein or coupled thereto.

26. The nanoparticle of claim 22 , wherein the therapeutic agent is a small molecule chemotherapeutic agent or a polynucleotide.

27. The nanoparticle of claim 25 , wherein the therapeutic agent is genomic DNA, cDNA, mRNA, siRNA, shRNA, miRNA, an antisense oligonucleotide, a viruses, or a chimeric polynucleotide.

28. The nanoparticle of claim 25 , wherein the therapeutic agent is an interfering RNA.

29. The nanoparticle of claim 25 , wherein the therapeutic agent comprises camptothecin, doxorubicin, or taxol.

30. An aqueous solution or dispersion of a plurality of nanoparticles of claim 22 .

31. The aqueous solution of dispersion of claim 30 , wherein each nanoparticle further comprises a therapeutic agent incorporated therein or coupled thereto.

32. The aqueous solution of dispersion of claim 30 , wherein therapeutic agent is a small molecule chemotherapeutic agent or a polynucleotide.

33. The aqueous solution of dispersion of claim 30 , wherein therapeutic agent is an interfering RNA.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 8, 2018
From: DAVIS, MARK E.; ALABI, CHRISTOPHER AKINLEYE
To: CALIFORNIA INSTITUTE OF TECHNOLOGY
Reel/Frame 046580/0430 →
CONFIRMATORY LICENSE Recorded Jul 23, 2015
From: CALIFORNIA INSTITUTE OF TECHNOLOGY
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 036160/0709 →
Continuity (5)
Continuation 14509118 · Oct 8, 2014
Continuation 13852303 · Mar 28, 2013
Division 12540319 · Aug 12, 2009
Provisional Application 61188855 · Aug 13, 2008
Related Publication 20150322207A1 · Nov 12, 2015