IP Library Granted Patent US 9,388,104
Granted Patent B2
US 9,388,104 · App. 14/248,245 · Granted Jul 12, 2016

Chemically modified small molecules

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Quick Facts
Patent No.
US 9,388,104
App. No.
14/248,245
Granted
Jul 12, 2016
Kind
B2
Abstract

Provided are methods of preparing a monodisperse oligo (ethylene glycol) reagent composition.

Claims (20)

1. A method of preparing a monodisperse oligo (ethylene glycol) reagent composition, comprising:

reacting a halo-terminated oligo (ethylene glycol) having (m) monomer subunits and a methoxy end-capping group with a first hydroxyl-terminated oligo (ethylene glycol) having (n) monomer subunits, wherein the first hydroxyl-terminated oligo (ethylene glycol) structure is HO—(CH 2 CH 2 O) n —H, under conditions effective to displace said halo group to thereby form an oligo (ethylene glycol) having (m)+(n) monomer subunits (OEG m+n ), wherein reacting the halo-terminated oligo(ethylene glycol) with the first hydroxyl-terminated oligo (ethylene glycol) comprises adding a 1:1 molar ratio of the halo-terminated oligo(ethylene glycol) to the first hydroxyl-terminated oligo (ethylene glycol) in a solution;

converting the terminal hydroxyl group of OEG m+n into a halo group, —X, to form OEG m+n -X; and

reacting OEG m+n -X with a second hydroxyl-terminated oligo (ethylene glycol) having (n) monomer subunits, wherein the second hydroxyl-terminated oligo structure is HO—(CH 2 CH 2 O) n —H, under conditions effective to displace said halo group to thereby form an oligo(ethylene glycol) having (m)+2(n) monomer subunits (OEG m+2n ), wherein reacting the OEG m+n -X with the second hydroxyl-terminated oligo (ethylene glycol) comprises adding a 1:1 molar ratio of the OEG m+n -X to the second hydroxyl-terminated oligo (ethylene glycol) in a solution;

wherein (m) and (n) each independently range from 1-10, and

wherein (OEG m+2n ) corresponds to the structure CH 3 O(CH 2 CH 2 O) m+2n H, and is present as part of a monodisperse composition of CH 3 O(CH 2 CH 2 O) m+2n H.

2. A method of preparing a monodisperse oligo (ethylene glycol) reagent composition, comprising:

reacting a halo-terminated oligo (ethylene glycol) having (m) monomer subunits and a methoxy end-capping group with a first hydroxyl-terminated oligo (ethylene glycol) having (n) monomer subunits, wherein the first hydroxyl-terminated oligo (ethylene glycol) structure is HO—(CH 2 CH 2 O) n —H, under conditions effective to displace said halo group to thereby form an oligo (ethylene glycol) having (m)+(n) monomer subunits (OEG m+n ), wherein reacting the halo-terminated oligo(ethylene glycol) with the first hydroxyl-terminated oligo (ethylene glycol) comprises adding a 1:1 molar ratio of the halo-terminated oligo(ethylene glycol) to the first hydroxyl-terminated oligo (ethylene glycol) in a solution;

converting the terminal hydroxyl group of OEG m+n into a halo group, —X, to form OEG m+n -X;

reacting OEG m+n -X with a second hydroxyl-terminated oligo (ethylene glycol) having (n) monomer subunits under conditions effective to displace said halo group to thereby form an oligo(ethylene glycol) having (m)+2(n) monomer subunits (OEG m+2n ), wherein OEG m+2n possesses a primary or secondary hydroxyl group, wherein reacting the OEG m+n -X with the second hydroxyl-terminated oligo (ethylene glycol) comprises adding a 1:1 molar ratio of the OEG m+n -X to the second hydroxyl-terminated oligo (ethylene glycol) in a solution;

converting said primary or secondary hydroxyl group into a halo group, —X, to form OEG m+2n -X; and

reacting OEG m+2n -X with a third hydroxyl-terminated oligo (ethylene glycol) having (n) monomer subunits under conditions effective to displace said halo group to thereby form an oligo (ethylene glycol) having m+3n monomer subunits (OEG m+3n ), wherein reacting the OEG m+2n -X with the third hydroxyl-terminated oligo (ethylene glycol) comprises adding a 1:1 molar ratio of the OEG m+2n -X to the third hydroxyl-terminated oligo (ethylene glycol) in a solution;

wherein (m) and (n) each independently range from 1-10; and

wherein (OEG m+3n ) corresponds to the structure CH 3 O(CH 2 CH 2 O) m+3n H, and is present as a monodisperse composition of CH 3 O(CH 2 CH 2 O) m+3n H.

3. The method of claim 1 , wherein (m) ranges from 1-3 and (n) ranges from 2-6.

4. The method of claim 2 , wherein (m) ranges from 1-3 and (n) ranges from 2-6.

5. The method of claim 1 , wherein each reacting step is carried out in the presence of a strong base.

6. The method of claim 2 , wherein each reacting step is carried out in the presence of a strong base.

7. The method of claim 1 , wherein each of the halo groups is Br.

8. The method of claim 2 , wherein each of the halo groups is Br.

Assignments (5)
RELEASE OF SECURITY INTEREST Recorded Jul 19, 2024
From: HCR REDHILL SPV, LLC
To: REDHILL BIOPHARMA INC.; REDHILL BIOPHARMA LTD.
Reel/Frame 068034/0458 →
SECURITY INTEREST Recorded Jul 10, 2024
From: HCR COLLATERAL MANAGEMENT, LLC, AS ADMINISTRATIVE AGENT
To: HCR REDHILL SPV, LLC, AS SUCCESSOR ADMINISTRATIVE AGENT
Reel/Frame 067953/0105 →
RELEASE OF SECURITY INTEREST Recorded Apr 17, 2020
From: TC LENDING, LLC, AS COLLATERAL AGENT
To: NEKTAR THERAPEUTICS
Reel/Frame 053180/0009 →
SECURITY INTEREST Recorded Feb 24, 2020
From: REDHILL BIOPHARMA INC.
To: HCR COLLATERAL MANAGEMENT, LLC, AS ADMINISTRATIVE AGENT
Reel/Frame 051909/0460 →
GRANT OF SECURITY INTEREST IN UNITED STATES PATENTS Recorded Oct 6, 2015
From: NEKTAR THERAPEUTICS
To: TC LENDING, LLC, AS COLLATERAL AGENT
Reel/Frame 036796/0562 →