# US 2022/0033448 A1 · Methods for aggregation of proteins

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 2022/0033448 A1
- Document ID: US20220033448A1
- Status: Published application
- Kind: A1
- Application number: 17/402,016
- Filed: 2021-08-13
- Published: 2022-02-03
- Earliest claimed: 2011-03-11
- Assignees: Vib Vzw; Vrije Universiteit Brussel; Katholieke Universiteit Leuven, KU LEUVEN R&D; Universiteit Gent
- Applicants: Vib Vzw; Vrije Universiteit Brussel; Katholieke Universiteit Leuven, K.U. Leuven R&D; Universiteit Gent
- Inventors: Joost Schymkowitz; Frederic Rousseau
- Web page: https://patentgrep.com/patent/US20220033448A1

## CPC

- C07K 14/40: from Candida
- A61L 27/00: Materials for {grafts or} prostheses or for coating {grafts or} prostheses (dental prostheses A61C13/00; shape or structure of prostheses A61F2/00; use of preparations for artificial teeth A61K6/80; artificial kidneys A61M1/14)
- A61L 29/16: Biologically active materials, e.g. therapeutic substances {(A61L29/048 takes precedence)}
- A61L 31/08: Materials for coatings
- A61L 31/16: Biologically active materials, e.g. therapeutic substances {(A61L31/047 takes precedence)}
- A61P 27/02: Ophthalmic agents
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 31/04: Antibacterial agents
- A61P 31/10: Antimycotics
- A61P 31/12: Antivirals
- A61P 35/00: Antineoplastic agents
- A61L 2300/25: Peptides having up to 20 amino acids in a defined sequence
- A61L 2300/404: Biocides, antimicrobial agents, antiseptic agents
- C07K 2319/21: containing a His-tag
- C07K 2319/42: containing a HA(hemagglutinin)-tag
- C07K 2319/43: containing a FLAG-tag
- 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)
- A61L: METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES (preservation of bodies or disinfecting characterised by the agents employed A01N; preserving, e.g. sterilising, food or foodstuffs A23; preparations for medical, dental or toiletry purposes A61K)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present application belongs to the field of functional peptides and more particularly to the field of controlled protein aggregation. The invention discloses molecules of a peptide structure as defined in the claims and methods of using such molecules for therapeutic applications and for diagnostic uses, as well as in other applications such as in the agbio field and in industrial biotechnology. The molecules can be used for curing and/or stabilizing infections such as bacterial,fimgal and viral diseases, but are also useful in non-infectious human and veterinary diseases. The molecules can also be used for the detection of protein biomarkers and for the prognosis and diagnosis of a variety of diseases.

## Claims

### Claim at position 1

-76. (canceled)

### Claim 77

A method for down-regulating the biological function of a protein, comprising
(a) contacting the protein with a molecule of structure (B), (C), (D), or (E):
(B) Z0—X1—Y1—X2—Z1—X3—Y2—X4—Z2, wherein Z1 is a linker and Z2 is selected from a linker or nothing,
(C) Z0—X1—Y1—X2—Z1—X3—Y2—X4—Z2—X5—Y3—X6—Z3, wherein Z1 and Z2 are each independently a linker and Z3 is selected from a linker or nothing,
(D) Z0—X1—Y1—X2—Z1—X3—Y2—X4—Z2—X5—Y3—X6—Z3—X7—Y4—X8—Z4, wherein Z1, Z2, and Z3 are each independently a linker and Z4 is selected from a linker or nothing,
(E) Z0—X1—Y1—X2—Z1—X3—Y2—X4—Z2—X5—Y3—X6—Z0—Y4-X8—Z4—X0—Y5—X10—Z5, wherein Z1, Z2, Z3, and Z4 are each independently a linker and Z5 is selected from a linker or nothing
wherein:
Z0 is a linker or nothing,
at least one of Y1, Y2, Y3, Y4, and Y5 is identical to, or differs by 1 or 2 amino acid substitutions from, a stretch of contiguous amino acids naturally occurring in the protein,
X1, X2, X3, X4, X5, X6, X7, X8, X9, and X10 are independently selected from 1 to 4 contiguous amino acids selected from arginine (R), lysine (K), glutamatic acid (E), aspartic acid (D), or proline (P),
Y1, Y2, Y3, Y4, and Y5, are independently selected from a stretch of 6 to 16 contiguous amino acids, wherein:
at least 50% of the contiguous amino acids are hydrophobic amino acids,
at least one aliphatic residue or phenylalanine (F) is present, and
if only one aliphatic residue or F is present, then at least one other residue is selected from tyrosine (Y), tryptophan (W), alanine (A), methionine (M) and threonine (T), and each of Y1, Y2, Y3, Y4, and Y5 contains no more than 1 each of a P, R, K, D or E residue, and
the molecule is devoid of a carrier or solubilizing moiety and
(b) inducing co-aggregation with the protein, thereby down-regulating the biological function of the protein.

### Claim 78 (depends on 77)

The method of claim 77, wherein the down-regulating of the biological function is functional inhibition.

### Claim 79 (depends on 77)

The method of claim 77, wherein the protein is a disease-related protein.

### Claim 80 (depends on 79)

The method of claim 79, wherein the disease-related protein is a protein whose overexpression is causatively linked to cancer.

### Claim 81 (depends on 79)

The method of claim 79, wherein the disease-related protein is a protein whose overexpression is causatively linked to age-related macular degeneration (AMD).

### Claim 82 (depends on 77)

The method of claim 77, the disease-related protein is a protein whose overexpression is causatively linked to inflammation or an inflammatory disease.

### Claim 83 (depends on 77)

The method of claim 77, wherein X1, X2, X3, X4, X5, X6, X7, X8, X9, and X10 are 1 or 2 amino acids.

### Claim 84 (depends on 77)

The method of claim 77, wherein Z1 in molecule (B), Z1 and Z2 in molecule (C) , Z1, Z2, and Z3 in molecule (D), and Z1, Z2, Z3, and Z4 in molecule (E) are each independently selected from a stretch of between 0 and 20 identical or non-identical units, wherein a unit is an amino acid, a monosaccharide, a nucleotide or a monomer.

### Claim 85 (depends on 77)

The method of claim 77, wherein the molecule is of structure (B), Z1 is a linker and Z2 is nothing or), Z0 is nothing and Z2 is nothing.

### Claim 86 (depends on 77)

The method of claim 77, further comprising a detectable label as an N- or C-terminal fusion to the molecule.

### Claim 87 (depends on 77)

The method of claim 77, wherein at least one of Y1, Y2, Y3, Y4, and Y5 is identical to a stretch of contiguous amino acids naturally occurring in the protein.

### Claim 88 (depends on 77)

The method of claim 77, wherein in molecules (B), (C), (D), and (E), X1, X2, X3, X4, X5, X6, X7, X8, X9, and Xio are independently selected from 1 to 4 contiguous amino acids selected from R, D, or P.

### Claim 89 (depends on 77)

The method of claim 77, wherein in molecules (B), (C), (D), and (E), each of Y1, Y2, Y3, Y4, and Y5 contains no P, R, K, D or E residue.

### Claim 90 (depends on 77)

The method of claim 77, wherein at least one of Y1, Y2, Y3, Y4, and Y5 differs by 1 amino acid substitution from a stretch of contiguous amino acids naturally occurring in the protein.

### Claim 91 (depends on 77)

The method of claim 77, wherein at least one of Y1, Y2, Y3, Y4, and Y5 differs by 2 amino acid substitutions from a from a stretch of contiguous amino acids naturally occurring in the protein.

### Claim 92 (depends on 77)

The method of claim 77, wherein at least two of Y1, Y2, Y3, Y4, and Y5 are each independently identical to a stretch of contiguous amino acids naturally occurring in the protein, or each independently differ by 1 or 2 amino acid substitutions from a stretch of contiguous amino acids naturally occurring in the protein.

### Claim 93 (depends on 92)

The method of claim 92, wherein at least one of Y1, Y2, Y3, Y4, and Y5 differs by 1 amino acid substitution from a stretch of contiguous amino acids naturally occurring in the protein.

### Claim 94 (depends on 92)

The method of claim 92, wherein at least one of Y1, Y2, Y3, Y4, and Y5 differs by 2 amino acid substitutions from a stretch of contiguous amino acids naturally occurring in the protein.

### Claim 95 (depends on 77)

The method of claim 77, where in Y1, Y2, Y3, Y4 and Y5 are independently selected from a stretch of 6 to 16 contiguous amino acids, at least 50% of which are hydrophobic amino acids, wherein at least one aliphatic residue or F is present, and if only one aliphatic residue or F is present, then at least two other residues are selected from Y, W, A, M and T, and each of Y1, Y2, Y3, Y4 and Y5 contains no more than 1 each of P, R, K, D or E residue.

### Claim 96 (depends on 77)

The method of claim 77, wherein Y1, Y2, Y3, Y4 and Y5 are independently selected from a stretch of 6 to 16 contiguous amino acids, at least 50% of which are hydrophobic amino acids, wherein at least one aliphatic residue or F is present, and if only one aliphatic residue or F is present, then at least one other residue are selected from Y, W, A, M and T, and each of Y1, Y2, Y3, Y4 and Y5 contains no more than 1 each of P, R, K, D or E residue.

### Claim 97 (depends on 77)

The method of claim 77, wherein at least one of Y1, Y2, Y3, Y4 and Y5 is identical to, or differs by 1 or 2 amino acid substitutions from, a stretch of contiguous amino acids naturally occurring in the protein.