# US 9,751,945 B2 · Sortase-modified VHH domains and uses thereof

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

- Number: US 9,751,945 B2
- Document ID: US9751945B2
- Status: Granted
- Kind: B2
- Application number: 14/394,046
- Filed: 2013-04-15
- Published: 2015-03-26
- Granted: 2017-09-05
- Earliest claimed: 2012-04-13
- Assignees: Whitehead Institute for Biomedical Research
- Applicants: Whitehead Institute for Biomedical Research
- Inventors: Hidde Ploegh; Maximilian Popp; Juanjo Cragnolini
- Web page: https://patentgrep.com/patent/US9751945B2

## CPC

- C07K 16/2833: {against MHC-molecules, e.g. HLA-molecules}
- A61K 47/6849: {the antibody targeting a receptor, a cell surface antigen or a cell surface determinant}
- A61K 47/6851: {the antibody targeting a determinant of a tumour cell}
- A61P 37/02: Immunomodulators
- C07K 1/13: Labelling of peptides
- C07K 16/108: Orthomyxoviridae (F), e.g. influenza virus
- C07K 16/44: against material not provided for elsewhere {, e.g. haptens, metals, DNA, RNA, amino acids}
- C07K 16/468: {Immunoglobulins having two or more different antigen binding sites, e.g. multifunctional antibodies}
- C12N 9/52: derived from bacteria {or Archaea}
- G01N 33/582: {with fluorescent label}
- A61K 2039/505: {comprising antibodies}
- C07K 2317/22: from camelids, e.g. camel, llama or dromedary
- C07K 2317/569: Single domain, e.g. dAb, sdAb, VHH, VNAR or nanobody®
- C07K 2319/90: containing a motif for post-translational modification
- 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
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

In some aspects, polypeptides comprising single domain antibodies and methods of identifying single domain antibodies are provided. In some embodiments polypeptides comprising a single domain antibody and a sortase recognition sequence, are provided. In some aspects, products and methods of use in modulating the immune system, e.g., modulating an immune response, are provided.

## Claims

### Claim 1

A method of modulating the immune response of a subject to an antigen, the method comprising administering an agent comprising (a) a targeting moiety A comprising a VHH that binds to MHCII complexes HLA-DR1, HLA-DR2 and HLA-DR4, wherein the VHH comprises SEQ ID NO: 59 or competes for binding to MHCII complexes HLA-DR1, HLA-DR2 and HLA-DR4 with a VHH comprising SEQ ID NO: 59; and (b) an antigen B that comprises a polypeptide, polysaccharide, or lipid that is from a pathogen or tumor cell, wherein the targeting moiety A and antigen B are physically associated with each other, or a composition comprising the agent and an adjuvant to the subject.

### Claim 2 (depends on 1)

The method of claim 1, wherein the targeting moiety A further comprises that binds to MHCII complex an antibody, an antibody chain, an antibody fragment, an scFv, a VHH domain, a single-domain antibody, an adnectin, or an aptamer, that binds to an MHCII complex.

### Claim 3 (depends on 1)

The method of claim 1, wherein the targeting moiety A comprises a VHH domain.

### Claim 4 (depends on 1)

The method of claim 1, wherein the antigen obtained from a pathogen.

### Claim 5 (depends on 1)

The method of claim 1, wherein the antigen comprises a tumor antigenan.

### Claim 6 (depends on 1)

The method of claim 1, wherein the antigen comprises a peptide.

### Claim 7 (depends on 1)

The method of claim 1, wherein the subject is human.

### Claim 8 (depends on 1)

The method of claim 1, wherein modulating the immune response comprises stimulating an immune response to the antigen.

### Claim 9 (depends on 1)

The method of claim 1, wherein the targeting moiety and the antigen are covalently linked.

### Claim 10 (depends on 1)

The method of claim 1, wherein the antigen is a viral antigen.

### Claim 11 (depends on 1)

The method of claim 1, wherein the antigen is a bacterial antigen.

### Claim 12 (depends on 1)

The method of claim 1, wherein the antigen is an envelope protein, capsid protein, secreted protein, structural protein, cell wall protein, cell wall polysaccharide, capsule protein, capsule polysaccharide, enzyme, or toxin.

### Claim 13 (depends on 1)

The method of claim 1, wherein the antigen comprises a fragment at least 15 amino acids long of a viral, bacterial, fungal, or parasite polypeptide.

### Claim 14 (depends on 1)

The method of claim 1, wherein the antigen comprises a recombinantly produced polypeptide.

### Claim 15 (depends on 1)

The method of claim 1, wherein the polypeptide, polysaccharide, or lipid is isolated from a source from which it originates.
