# US 10,870,679 B2 · Modulation of structured polypeptide specificity

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- Number: US 10,870,679 B2
- Document ID: US10870679B2
- Status: Granted
- Kind: B2
- Application number: 16/013,795
- Filed: 2018-06-20
- Published: 2018-12-20
- Granted: 2020-12-22
- Earliest claimed: 2013-04-11
- Assignees: BicycleRD Limited
- Applicants: BicyleRD Limited
- Inventors: Daniel Paul Teufel; Catherine Stace; Edward Walker; John Tite
- Web page: https://patentgrep.com/patent/US10870679B2

## CPC

- C07K 7/08: having 12 to 20 amino acids (gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68)
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 11/02: Nasal agents, e.g. decongestants
- A61P 17/00: Drugs for dermatological disorders
- A61P 17/04: Antipruritics
- A61P 27/02: Ophthalmic agents
- A61P 27/16: Otologicals
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P 35/00: Antineoplastic agents
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- A61P 37/08: Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14)
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07K 7/06: having 5 to 11 amino acids
- C07K 7/50: Cyclic peptides containing at least one abnormal peptide link
- C07K 7/54: with at least one abnormal peptide link in the ring
- C12N 9/6445: {Kallikreins (3.4.21.34; 3.4.21.35)}
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

The invention describes peptide ligands specific for human plasma Kallikrein.

## Claims

### Claim 1

A peptide ligand specific for human Kallikrein comprising a polypeptide comprising three reactive groups, separated by two loop sequences, and a molecular scaffold which forms covalent bonds with the reactive groups of the polypeptide such that two polypeptide loops are formed on the molecular scaffold, wherein the loops of the peptide ligand comprise five amino acids and wherein the polypeptide comprises the motif Grx1x2x3x4x5Grx6x7x8x9x10Gr, wherein x1 and x9 are independently any amino acid, x2 is tryptophan or phenylalanine, x3 is proline or azetidine carboxylic acid, x4 is alanine or tyrosine, x5 is arginine, N-methyl arginine, homoarginine, or guanidylphenylalanine, x6 is tyrosine, leucine or alanine, x7 is histidine, x8 is glutamine or threonine, x10 is leucine, and Gr represents cysteine; and wherein the peptide bond between x6 and x7 is replaced by ΨCH2NH.

### Claim 2 (depends on 1)

The peptide ligand according to claim 1, wherein in the first loop x3 is azetidine carboxylic acid; and/or in the first loop x5 is N-methyl arginine or homoarginine or guanidylphenylalanine.

### Claim 3 (depends on 2)

The peptide ligand according to claim 2, wherein the polypeptide comprises a first loop which comprises the motif Grx1Fx3Yx5Gr (SEQ ID NO: 6), wherein x3 is azetidine carboxylic acid and/or x5 is N-methyl arginine or homoarginine or guanidylphenylalanine.

### Claim 4 (depends on 1)

The peptide ligand according to claim 1, wherein the molecular scaffold is a tris(bromomethyl)benzene, or a derivative thereof.

### Claim 5 (depends on 4)

The peptide ligand according to claim 4, wherein the molecular scaffold is 1,3,5-tris(bromomethyl)-2,4,6-trimethylbenzene, 1,3,5-tris(bromomethyl)benzene, or 1,3,5-tris(bromomethyl)-2,4,6-triethylbenzene.

### Claim 6 (depends on 4)

The peptide ligand according to claim 4, wherein the molecular scaffold is 1,3,5-tris(bromomethyl)benzene.

### Claim 7 (depends on 1)

The peptide ligand according to claim 1, wherein the peptide ligand is attached to an antibody or a fragment thereof.

### Claim 8 (depends on 7)

The peptide ligand according to claim 7, wherein in the first loop x3 is azetidine carboxylic acid; and/or in the first loop x5 is N-methyl arginine or homoarginine or guanidylphenylalanine.

### Claim 9 (depends on 7)

The peptide ligand according to claim 7, wherein the polypeptide comprises a first loop which comprises the motif Grx1Fx3Yx5Gr (SEQ ID NO: 6), wherein x3 is azetidine carboxylic acid and/or x5 is N-methyl arginine or homoarginine or guanidylphenylalanine.

### Claim 10 (depends on 7)

The peptide ligand according to claim 7, wherein the peptide ligand comprises: Cys Ser1 Phe 2 Aze3 Tyr4 HArg5 Cys Ala(ΨCH2NH)6 His7 Gln8 Asp9 Leu10 Cys (SEQ ID NO: 201).

### Claim 11 (depends on 7)

The peptide ligand according to claim 7, wherein the antibody fragment is selected from an antibody light chain constant region (CL), an antibody CH1 heavy chain domain, an antibody CH2 heavy chain domain, an antibody CH3 heavy chain domain, or any combination thereof, in addition to the one or more constant region domains.

### Claim 12 (depends on 7)

The peptide ligand according to claim 7, wherein the antibody or fragment thereof comprises a hinge region of an antibody.

### Claim 13 (depends on 12)

The peptide ligand according to claim 12, wherein the hinge region comprises the region between the CH1 and CH2 domains of an IgG molecule.

### Claim 14 (depends on 7)

The peptide ligand according to claim 7, wherein the antibody or fragment thereof comprises an Fc region of an IgG molecule.

### Claim 15 (depends on 7)

The peptide ligand according to claim 7, wherein the peptide ligand comprises:

### Claim 16 (depends on 15)

The peptide ligand according to claim 15, wherein the peptide ligand is attached to an antibody or a fragment thereof, wherein the antibody fragment is selected from an antibody light chain constant region (CL), an antibody CH1 heavy chain domain, an antibody CH2 heavy chain domain, an antibody CH3 heavy chain domain, or any combination thereof, in addition to the one or more constant region domains.

### Claim 17 (depends on 15)

The peptide ligand according to claim 15, wherein the peptide ligand is attached to an antibody or a fragment thereof, which comprises a hinge region of an antibody.

### Claim 18 (depends on 17)

The peptide ligand according to claim 17, wherein the hinge region comprises the region between the CH1 and CH2 domains of an IgG molecule.

### Claim 19 (depends on 15)

The peptide ligand according to claim 15, wherein the peptide ligand is attached to an antibody or a fragment thereof, which comprises an Fc region of an IgG molecule.

### Claim 20 (depends on 1)

A pharmaceutical composition comprising the peptide ligand according to claim 1 and a pharmacologically appropriate carrier.

### Claim 21 (depends on 7)

A pharmaceutical composition comprising the peptide ligand according to claim 7 and a pharmacologically appropriate carrier.