IP Library Granted Patent US 8,445,544
Granted Patent B2
US 8,445,544 · App. 12/688,461 · Granted May 21, 2013

Hydrolysable polymeric FMOC-linker

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Quick Facts
Patent No.
US 8,445,544
App. No.
12/688,461
Granted
May 21, 2013
Kind
B2
Abstract

The invention relates to Fmoc (9-fluorenyl-methoxycarbonyl)-based polymeric conjugates. These conjugates are useful for extending the in-vivo circulation of protein and peptide drugs.

Claims (23)

1. A process for the preparation of a compound of formula (2)

said process comprising the step of subjecting a compound of formula:

and an intermediate compound having a formula

to a coupling reaction to form the compound of formula (2),

wherein

PSA is polysialic acid;

R 1 is at each occurrence independently a (C 1 -C 8 )-alkyl;

R 2 is independently selected from the group consisting of —C(O)NR—, —C(O)NR—(C 1 -C 8 )-alkyl-NR—, —NRC(O)— and —NRC(O)—(C 1 -C 8 )-alkyl-NR,

R is independently either hydrogen or (C 1 -C 8 )-alkyl;

X is —SO 3 —R 3 ;

R 3 is independently selected from the group consisting of hydrogen, (C 1 -C 8 )-alkyl and (C 1 -C 8 )-alkyl-R 4 ;

R 4 is a polymer,

n is an integer selected from 0, 1, 2, 3, or 4; and

m is an integer selected from 1, 2, 3, or 4.

2. The process according to claim 1 , wherein R 2 is either —C(O)NR— or —NRC(O)— and wherein R is independently either hydrogen or C 1 -C 8 -alkyl.

3. The process according to claim 1 , further comprising reacting the compound of formula (2) and a protein or peptide drug to form a protein or peptide drug conjugate having the formula:

4. The process according to claim 3 , wherein the protein or peptide drug is selected from the group consisting of Factor VII, von Willebrand Factor (VWF), Factor VIIa, Factor VIII, and Factor IX.

5. The process according to claim 1 , wherein the PSA has a molecular weight of 5000 to 25000 Dalton.

6. The process according to claim 1 , wherein the PSA has a molecular weight of 5000 to 10000 Dalton.

7. The process according to claim 3 , wherein the PSA has a molecular weight of 5000 to 25000 Dalton.

8. The process according to claim 3 , wherein the PSA has a molecular weight of 5000 to 10000 Dalton.

9. The process according to claim 5 , wherein the PSA has a molecular weight of 5000 to 25000 Dalton.

10. The process according to claim 5 , wherein the PSA has a molecular weight of 5000 to 10000 Dalton.

Assignments (4)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 31, 2021
From: BAXALTA GMBH; BAXALTA INCORPORATED
To: TAKEDA PHARMACEUTICAL COMPANY LIMITED
Reel/Frame 055189/0005 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 17, 2015
From: BAXTER HEALTHCARE SA
To: BAXALTA GMBH; BAXALTA INCORPORATED
Reel/Frame 036362/0001 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 17, 2015
From: BAXTER INTERNATIONAL INC.
To: BAXALTA GMBH; BAXALTA INCORPORATED
Reel/Frame 036374/0001 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 14, 2013
From: TURECEK, PETER; SIEKMANN, JUERGEN
To: BAXTER INTERNATIONAL INC.; BAXTER HEALTHCARE S.A.
Reel/Frame 029810/0921 →