Polyfluoreno[4,5-cde]oxepine polymers and conjugates thereof

Patent metadata

Field	Value
Publication number	US-9896538-B2
Application number	US-201715469952-A
Country	US
Kind code	B2
Filing date	Mar 27, 2017
Priority date	Mar 28, 2016
Publication date	Feb 20, 2018
Grant date	Feb 20, 2018

Abstract

The invention provides for polyfluoreno[4,5-cde]oxepine conjugates and their use in methods of analyte detection.

First claim

What is claimed is:

1. A polymer comprising monomers
of formula A

wherein X is the number of monomer A units in the polymer wherein the monomer units are consecutive or nonconsecutive and wherein X is from 6 to 100; and one or more monomers selected from the group consisting of
monomer of formula B

wherein Y is the number of monomer B units in the polymer wherein the monomer units are consecutive or nonconsecutive and wherein Y is from 0 to 99; and
monomer of formula C

wherein Z is the number of monomer C units in the polymer wherein the monomer units are consecutive or nonconsecutive and wherein Z is from 0 to 99;
wherein R1 to R6 independently is hydrogen, an alkyl, a polyethyleneglycol (PEG), an aryl, a heteroaryl group, or a biological substrate conjugated via a linker (L-BS);
wherein SG1 to SG6 independently is an alkyl, a water soluble group or a L-BS; and
wherein the polymer includes end groups HG1 and HG2 wherein HG1 and HG2 independently is a hydrogen, an alkyl, a halogen, a boronyl, an aryl, a heteroaryl group or a L-BS;
wherein the ratio of X to Y+Z is >1,
wherein the sum of X+Y+Z is >10.

2. The polymer of claim 1 , wherein the polymer comprises an L-BS and the ratio of BS to polymer is 0.2-3.

3. The polymer of claim 1 wherein monomer unit B and monomer unit C are different.

4. The polymer of claim 1 , wherein the monomer units are directly connected to one another.

5. The polymer of claim 1 , wherein the linker comprises an alkyl, a PEG, a carboxamide, a thioether, an ester, an imine, a hydrazine, an oxime, an alkyl amine, an ether, an aryl amine, a boronate ester, an N-acylurea or anhydride, a platinum complex, an aminotriazine, a triazinyl ether, an amidine, a urea, a urethane, a thiourea, a phosphite ester, a silyl ether, a sulfonamides, a sulfonate ester, a 1,2,3-triazole, a pyradazine, a thiazolidine, a 2-diphenylphosphonyl-benzoamide, an isoxazole or a succinimide group.

6. The polymer according to claim 1 , wherein:
(i) R1 to R6 independently represent hydrogen, methyl, or ethyl; and/or
(ii) SG1 to SG6 independently represent a PEG, an alkyl, a carboxyalkyl, a sulfonylalkyl, a phosphonylalkyl, an aminoalkyl or L-BS; and/or
(iii) L is an alkyl chain or a PEG chain; and/or
(iv) BS is an antibody, a peptide, a protein, an oligonucleotide, a nucleic acid or a carbohydrate; and/or
(v) HG1 and HG2 independently represent a hydrogen, an aryl, a halogen or a boronyl; and/or
(vi) x is an integer from 11-80 and y and z are each an integer independently selected from 0-80, provided that (1) the ratio of BS/polymer is 1-2, (2) the ratio of x/(y+z) is >1, and (3) the sum of x+y+z is >20.

7. The polymer according to claim 1 , wherein:
(i) R1 to R6 are hydrogen; and/or
(ii) SG1 and SG2 are PEG; and/or
(iii) SG3 to SG6 independently represent a PEG, an alkyl, a carboxyalkyl, a sulfonylalkyl, a phosphonylalkyl, an aminoalkyl or a L-BS.

8. The polymer according to claim 1 , wherein:
(i) SG3 to SG6 independently represent a PEG, an alkyl, a carboxyalkyl, or a L-BS; or
(ii) SG3 to SG6 independently represent a PEG, an alkyl, an aminoalkyl or a L-BS.

9. The polymer of claim 8 , wherein alkyl is a methyl group.

10. The polymer of claim 1 , wherein R1 to R6 are hydrogen; wherein SG1 to SG6 independently represent a PEG, an alkyl, a carboxyalkyl, a sulfonylalkyl, a phosphonylalkyl, or an aminoalkyl; wherein HG1 and HG2 independently represent a hydrogen, an aryl, a halogen, a boronyl or a L-BS; wherein L comprises an alkyl chain or a PEG chain; wherein BS is an antibody, a peptide, a protein, an oligonucleotide, a nucleic acid or a carbohydrate; and wherein x is an integer from 16-80 and y and z are each an integer independently selected from 0-80, provided that (1) the ratio of BS/polymer is 1-2, (2) the ratio of x/(y+z) is >1, and (3) the sum of x+y+z is >20.

11. The polymer according to claim 1 , wherein SG1 and SG2 are independently PEG6 to PEG18.

12. The polymer according to claim 1 , wherein the ratio of BS/polymer is 1; x is an integer from 16-80, y and z are each an integer independently selected from 0-64 and wherein the sum of x+y+z is 30-80.

13. The polymer according to claim 1 , wherein:
(i) HG1 and HG2 independently represent a hydrogen, a carboxyaryl, or a L-BS; or
(ii) HG1 and HG2 independently represent a halogen, a boronyl, a carboxyaryl, or a L-BS.

14. A polymer comprising monomers
of formula D

wherein W is the number of monomer D units in the polymer wherein the monomer units are consecutive or nonconsecutive and wherein W is from 6 to 100; and one or more monomers selected from the group consisting of
monomer of formula E

wherein X is the number of monomer E units in the polymer wherein the monomer units are consecutive or nonconsecutive and wherein X is from 0 to 98;
monomer of formula F

wherein Y is the number of monomer F units in the polymer wherein the monomer units are consecutive or nonconsecutive and wherein Y is from 1 to 20; and
monomer of formula G

wherein Z is the number of monomer G units in the polymer wherein the monomer units are consecutive or nonconsecutive and wherein Z is from 0 to 98; and
wherein R1 to R6 independently is hydrogen, an alkyl, a polyethyleneglycol (PEG), an aryl, a heteroaryl group, or a biological substrate conjugated via a linker (L-BS);
wherein SG1 to SG7 independently is an alkyl, a water soluble group or a L-BS; and
wherein the polymer includes end groups HG1 and HG2 wherein HG1 and HG2 independently is a hydrogen, an alkyl, a halogen, a boronyl, an aryl, a heteroaryl group or a L-BS;
wherein the ratio of W to X+Y+Z is >1,
wherein the sum of W+X+Y+Z is >10,
wherein FP is a fluorophore or fluorescent dye that has absorption maximum longer than 450 nm and emission maximum longer than 500 nm with fluorescence quantum yield greater than 5%.

15. The polymer of claim 14 , wherein the polymer comprises an L-BS and the ratio of BS to polymer is 0.2-3.

16. The polymer of claim 14 wherein monomer unit E and monomer unit G are different.

17. The polymer according to claim 14 , wherein the monomer units are directly connected to one another.

18. The polymer according to claim 14 , wherein the linker comprises an alkyl, a PEG, an FP, a carboxamide, a thioether, an ester, an imine, a hydrazine, an oxime, an alkyl amine, an ether, an aryl amine, a boronate ester, an N-acylurea or anhydride, a platinum complex, an aminotriazine, a triazinyl ether, an amidine, a urea, a urethane, a thiourea, a phosphite ester, a silyl ether, a sulfonamides, a sulfonate ester, a 1,2,3-triazole, a pyradazine, a thiazolidine, a 2-diphenylphosphonyl-benzoamide, an isoxazole or a succinimide

Assignees

• Aat Bioquest Inc
• Affymetrix Inc

Inventors

• Diwu Zhenjun
• Guo Haitao
• Peng Ruogu
• Zhao Qin
• Jennings Travis
• Funatake Castle

Classifications

• C08G2261/143

  Side-chains containing nitrogen · CPC title

• C08G2261/522

  fluorescent · CPC title

• C08G2261/77

  grafting · CPC title

• C08G2261/94

  Applications in sensors, e.g. biosensors · CPC title

• C08G2261/3242

  containing one or more oxygen atoms as the only heteroatom, e.g. benzofuran · CPC title