Albumin variants

Inactive Publication Date: 2014-05-08
NOVOZYMES BIOPHARMA DK AS
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The invention allows for the customization of the half-life of albumin and its variants to meet the needs of users. This is achieved by tailoring the binding affinity and half-life of the albumin. The patent describes various parameters that can be used to determine and compare the binding affinity, such as FcRn and coupling chemistry. The coupling method involves injecting the protein and using specific buffer solutions for regeneration of surfaces. Overall, the invention provides a flexible solution for creating customized albumin-based products with specific properties.

Problems solved by technology

.). However, the studies of Kenanova et al are limited to domain III of HSA and therefore do not consider HSA in its native intact configurat
ion. Furthermore, the identified positions result in a decrease in affinity for the FcRn rece

Method used

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  • Albumin variants
  • Albumin variants
  • Albumin variants

Examples

Experimental program
Comparison scheme
Effect test

embodiment 1

2. The polypeptide wherein the polypeptide comprises alterations at two or more positions selected from positions corresponding to positions (a) 492 and 580; (b) 492 and 574; (c) 492 and 550; (d) 550 and 573; (e) 550 and 574; (f) 550 and 580 in SEQ ID NO: 2.

3. The polypeptide according to embodiment 1 or 2 comprising alterations at positions corresponding to positions 492 and 580 of SEQ ID NO: 1, further comprising one or more (several) alterations at positions corresponding to positions selected from the group consisting of 550, 573 and 574 of SEQ ID NO: 2.

4. The polypeptide according to embodiment 1, 2 or 3 comprising alterations at positions corresponding to positions 492 and 574 of SEQ ID NO: 1, further comprising one or more (several) alterations at positions corresponding to positions selected from the group consisting 550, 573 and 580 of SEQ ID NO:

5. The polypeptide according to any preceding embodiment comprising alterations at positions corresponding to positions 492 and 5...

embodiment 14

15. The polypeptide of embodiment 14 wherein the substitution at the position corresponding to position 492 is to G, D, F, H, M or R.

16. The polypeptide of embodiment 14 or 15 wherein the substitution at the position corresponding to position 492 is to G or D.

17. The polypeptide of any of embodiments 13 to 15 wherein the substitution at the position corresponding to position 492 is to G.

18. The polypeptide of any of embodiments 13 to 15 wherein the substitution at the position corresponding to position 492 is to D.

19. The polypeptide of any of embodiments 13 to 18 wherein the substitution at the position corresponding to position 550 is to K, L, M E, or R.

20. The polypeptide of any of embodiments 13 to 19 wherein the substitution at the position corresponding to position 550 is to K, L or M.

21. The polypeptide of any of embodiments 13 to 20 wherein the substitution at the position corresponding to position 550 is to K.

22. The polypeptide of any of embodiments 13 to 21 wherein the al...

embodiment 32

33. The polypeptide of embodiment 32 wherein the polypeptide comprises alterations at positions corresponding to the following positions of SEQ ID NO: 2: 574H+580K+573P (e.g. SEQ ID NO: 135); 550K+574H+573P (e.g. SEQ ID NO: 131); 492D+550K+573P (e.g. SEQ ID NO: 253); 550M+573P+580K (e.g. SEQ ID NO: 252); 550L+573P+580K (e.g. SEQ ID NO: 253); 492G+573P+580K (e.g. SEQ ID NO: 242); 550M+573P+574H (e.g. SEQ ID NO: 250); 492G+550K+573P (e.g. SEQ ID NO: 254); 550L+573P+574H (e.g. SEQ ID NO: 246); 492D+573P+580K (e.g. SEQ ID NO: 234); 492D+573P+574H (e.g. SEQ ID NO: 233); 492G+574H+580K (e.g. SEQ ID NO: 263); 492G+550K+580K (e.g. SEQ ID NO: 259); 492D+550K+580K (e.g. SEQ ID NO: 258); 492D+574H+580K (e.g. SEQ ID NO: 262); or 492G+550K+574H (e.g. SEQ ID NO: 255).

34. The polypeptide according to any preceding embodiment wherein the polypeptide comprises four or more alterations at positions selected from the group consisting of positions corresponding to the following positions of SEQ ID NO: ...

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Abstract

The present invention relates to variants of a parent albumin, the variants having altered plasma half-life compared with the parent albumin. The present invention also relates to polynucleotides encoding the variants; nucleic acid constructs, vectors, and host cells comprising the polynucleotides; and methods of using the variants.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application claims priority or the benefit under 35 U.S.C. 119 of European application no. 12191856.9 filed Nov. 8, 2012 and U.S. provisional application No. 61 / 724,669 filed Nov. 9, 2012, the contents of which are fully incorporated herein by reference.REFERENCE TO A SEQUENCE LISTING[0002]This application contains a Sequence Listing in computer readable form, which is incorporated herein by reference.BACKGROUND OF THE INVENTION[0003]1. Field of the Invention[0004]The invention relates to variants of albumin or fragments thereof or fusion polypeptides comprising variant albumin or fragments thereof having a change in binding affinity to FcRn and / or a change in half-life compared to the albumin, fragment thereof or fusion polypeptide comprising albumin or a fragment thereof. The invention allows tailoring of binding affinity and / or half-life of an albumin to the requirements and desires of a user or application.[0005]2. Description of...

Claims

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Application Information

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IPC IPC(8): C07K14/765
CPCC07K14/765C07K2319/31A61K39/385A61K38/385C07K2319/00A61P43/00A61K38/00
InventorCAMERON, JASONDELAHAY, KAREN ANNNIELSEN, JENS ERIKPLUMRIDGE, ANDREWANDERSEN, JAN TERJE
OwnerNOVOZYMES BIOPHARMA DK AS