# US 10,501,524 B2 · Albumin variants

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- Number: US 10,501,524 B2
- Document ID: US10501524B2
- Status: Granted
- Kind: B2
- Application number: 14/685,112
- Filed: 2015-04-13
- Published: 2015-07-30
- Granted: 2019-12-10
- Earliest claimed: 2012-11-08
- Assignees: Albumedix Ltd
- Applicants: Albumedix Ltd
- Inventors: Jason Cameron; Karen Ann Delahay; Jens Erik Nielsen; Andrew Plumridge; Jan Terje Andersen
- Web page: https://patentgrep.com/patent/US10501524B2

## CPC

- C07K 14/765: Serum albumin, e.g. HSA
- A61K 39/385: Haptens or antigens, bound to carriers
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A61K 38/385: {Serum albumin}
- C07K 2319/00: Fusion polypeptide
- C07K 2319/31: fusions, other than Fc, for prolonged plasma life, e.g. albumin
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## 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.

## Claims

### Claim 1

A method of altering the binding activity of a polypeptide, which is a variant of albumin, a fragment thereof or a fusion polypeptide comprising said variant albumin or fragment thereof, to FcRn as compared with the FcRn binding activity of a parent albumin, reference albumin, fragment thereof or a fusion polypeptide comprising said parent albumin, reference albumin or fragment or fusion thereof, comprising contacting FcRn with said polypeptide, wherein said polypeptide further comprises a substitution to K, L, or M at a position corresponding to 550 in SEQ ID NO: 2, a substitution to P, Y, W, H, F, T, I, or V at a position corresponding to 573 in SEQ ID NO: 2, and a substitution to K or R at a position corresponding to 580 in SEQ ID NO: 2, wherein said polypeptide has a stronger binding affinity to FcRn or longer plasma half-life than a parent albumin, reference albumin, fragment thereof or fusion polypeptide comprising said parent albumin, reference albumin or fragment or fusion thereof.

### Claim 2 (depends on 1)

The method of claim 1, wherein within said polypeptide further comprises:
a) a substitution to A, C, D, E, F, G, H, I, L, M, N P, Q, R, S, T, V, W, or Y at a position corresponding to position 574 of SEQ ID NO: 2; or
b) a substitution to N at a position corresponding to position 574 of SEQ ID NO: 2, a substitution to K at a position corresponding to position 580 of SEQ ID NO: 2, and a substitution at a position corresponding to position 492 of SEQ ID NO: 2.

### Claim 3 (depends on 1)

The method of claim 1, wherein within said polypeptide further comprises:
a substitution to P at a position corresponding to position 573 of SEQ ID NO: 2, a substitution to K at a position corresponding to position 580 of SEQ ID NO: 2, and a substitution at a position corresponding to position 492 or 574 of SEQ ID NO: 2.

### Claim 4 (depends on 1)

The method of claim 1, wherein within said polypeptide further comprises:
a) a substitution to A, C, D, E, F, G, H, I, L, M, N, P, Q, R, S, T, V, W, or Y, at a position corresponding to position 492 of SEQ ID NO: 2; or
b) a substitution to N at a position corresponding to position 492 of SEQ ID NO: 2, a substitution to K at a position corresponding to position 573 of SEQ ID NO: 2, and a substitution at a position corresponding to position 574 of SEQ ID NO: 2.

### Claim 5 (depends on 1)

The method of claim 1, wherein said polypeptide further comprises a substitution at one or more positions selected from positions corresponding to positions 492 and 574 in SEQ ID NO: 2.

### Claim 6 (depends on 1)

The method of claim 1, wherein the reference albumin is HSA (SEQ ID NO: 2) or a fragment thereof, or a fusion polypeptide comprising HSA or a fragment thereof.

### Claim 7 (depends on 1)

The method of claim 1, wherein the sequence identity of said polypeptide to SEQ ID NO: 2 is more than 80%, more than 90%, more than 95%, more than 96%, more than 97%, more than 98% or more than 99%.

### Claim 8 (depends on 1)

The method of claim 1, wherein said fusion comprises a fusion partner polypeptide selected from a therapeutic, prophylactic, diagnostic, imaging or other beneficial moiety.

### Claim 9 (depends on 1)

The method of claim 1, wherein said polypeptide further comprises a non-albumin moiety covalently attached to said polypeptide.

### Claim 10 (depends on 1)

The method of claim 1, wherein said polypeptide further comprises a non-albumin moiety noncovalently associated with said polypeptide.

### Claim 11

A method for altering the circulating half-life of a molecule comprising providing a variant of albumin, a fragment thereof or a fusion polypeptide comprising said variant albumin or fragment thereof; and
a) where the molecule is a polypeptide, fusing or conjugating the molecule to said variant of albumin, fragment thereof or fusion polypeptide comprising said variant albumin or fragment thereof; or
b) where the molecule is not a polypeptide, conjugating the molecule to said variant of albumin, fragment thereof or fusion polypeptide comprising said variant albumin or fragment thereof; or
c) contacting the molecule with said variant of albumin, fragment thereof or fusion polypeptide comprising said variant albumin or fragment thereof, wherein said contacting results in a noncovalent association between said molecule and variant of albumin, fragment thereof or fusion polypeptide comprising said variant albumin or fragment thereof;
wherein said variant of albumin, fragment thereof or fusion polypeptide comprising said variant albumin or fragment thereof comprises a substitution to K, L, or M at a position corresponding to 550 in SEQ ID NO: 2, a substitution to P, Y, W, H, F, T, I, or V at a position corresponding to 573 in SEQ ID NO: 2, and a substitution to K or R at a position corresponding to 580 in SEQ ID NO: 2, wherein said polypeptide has a stronger binding affinity to FcRn or longer plasma half-life than a parent albumin, reference albumin, fragment thereof or fusion polypeptide comprising said parent albumin, reference albumin or fragment or fusion thereof.

### Claim 12 (depends on 11)

The method of claim 11, wherein within said polypeptide further comprises:
a) a substitution to A, C, D, E, F, G, H, I, L, M, N, P, Q, R, S, T, V, W, or Y at a position corresponding to position 574 of SEQ ID NO: 2; or
b) a substitution to N at a position corresponding to position 574 of SEQ ID NO: 2, a substitution to K at a position corresponding to position 580 of SEQ ID NO: 2, and a substitution at a position corresponding to position 492 of SEQ ID NO: 2.

### Claim 13 (depends on 11)

The method of claim 11, wherein within said polypeptide further comprises:
a substitution to P at a position corresponding to position 573 of SEQ ID NO: 2, a substitution to K at a position corresponding to position 580 of SEQ ID NO: 2, and a substitution at a position corresponding to a position selected from the group consisting of 492 and 574 of SEQ ID NO: 2.

### Claim 14 (depends on 11)

The method of claim 11, wherein within said polypeptide further comprises:
a) a substitution to A, C, D, E, F, G, H, I, L, M, N, P, Q, R, S, T, V, W, or Y at a position corresponding to position 492 of SEQ ID NO: 2; or
b) a substitution to N at a position corresponding to position 492 of SEQ ID NO: 2, a substitution to K at a position corresponding to position 573 of SEQ ID NO: 2, and a substitution at a position corresponding to position 574 of SEQ ID NO: 2.

### Claim 15 (depends on 11)

The method of claim 11, wherein said polypeptide further comprises a substitution at one or more positions selected from positions corresponding to positions 492 and 574 in SEQ ID NO: 2.

### Claim 16 (depends on 1)

The method of claim 1, wherein said variant of albumin, fragment thereof or fusion polypeptide comprising said variant albumin or fragment thereof comprises a substitution to P, Y, or W at a position corresponding to 573.

### Claim 17 (depends on 1)

The method of claim 1, wherein said variant of albumin, fragment thereof or fusion polypeptide comprising said variant albumin or fragment thereof comprises a substitution to P at a position corresponding to 573.

### Claim 18 (depends on 1)

The method of claim 1, wherein said variant of albumin, fragment thereof or fusion polypeptide comprising said variant albumin or fragment thereof comprises a substitution to L at a position corresponding to 550, a substitution to P at a position corresponding to 573, and a substitution to K at a position corresponding to 580.

### Claim 19 (depends on 11)

The method of claim 11, wherein said variant of albumin, fragment thereof or fusion polypeptide comprising said variant albumin or fragment thereof comprises a substitution to P, Y, or W at a position corresponding to 573.

### Claim 20 (depends on 11)

The method of claim 11, wherein said variant of albumin, fragment thereof or fusion polypeptide comprising said variant albumin or fragment thereof comprises a substitution to P at a position corresponding to 573.

### Claim 21 (depends on 11)

The method of claim 11, wherein said variant of albumin, fragment thereof or fusion polypeptide comprising said variant albumin or fragment thereof comprises a substitution to L at a position corresponding to 550, a substitution to P at a position corresponding to 573, and a substitution to K at a position corresponding to 580.

### Claim 22 (depends on 1)

The method of claim 1, wherein said variant of albumin, fragment thereof or fusion polypeptides comprising said variant albumin or fragment thereof comprises a substitution to M at a position corresponding to position 550 of SEQ ID NO: 2, a substitution to P at a position corresponding to position 573 of SEQ ID NO: 2, and a substitution to K at a position corresponding to position 580 of SEQ ID NO: 2.

### Claim 23 (depends on 1)

The method of claim 1, wherein said variant of albumin, fragment thereof or fusion polypeptides comprising said variant albumin or fragment thereof comprises a substitution to K at a position corresponding to position 550 of SEQ ID NO: 2, a substitution to P at a position corresponding to position 573 of SEQ ID NO: 2, and a substitution to K at a position corresponding to position 580 of SEQ ID NO: 2.

### Claim 24 (depends on 11)

The method of claim 11, wherein said variant of albumin, fragment thereof or fusion polypeptides comprising said variant albumin or fragment thereof comprises a substitution to M at a position corresponding to position 550 of SEQ ID NO: 2, a substitution to P at a position corresponding to position 573 of SEQ ID NO: 2, and a substitution to K at a position corresponding to position 580 of SEQ ID NO: 2.

### Claim 25 (depends on 11)

The method of claim 11, wherein said variant of albumin, fragment thereof or fusion polypeptides comprising said variant albumin or fragment thereof comprises a substitution to K at a position corresponding to position 550 of SEQ ID NO: 2, a substitution to P at a position corresponding to position 573 of SEQ ID NO: 2, and a substitution to K at a position corresponding to position 580 of SEQ ID NO: 2.