Sortase-modified VHH domains and uses thereof

Patent metadata

Field	Value
Publication number	US-9751945-B2
Application number	US-201314394046-A
Country	US
Kind code	B2
Filing date	Apr 15, 2013
Priority date	Apr 13, 2012
Publication date	Sep 5, 2017
Grant date	Sep 5, 2017

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.

First claim

What is claimed is:

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.

2. 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.

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

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

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

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

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

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

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

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

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

12. 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.

13. 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.

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

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

Assignees

• Whitehead Inst Biomedical Res

Inventors

• Ploegh Hidde
• Popp Maximilian
• Cragnolini Juanjo

Classifications

• C12N9/52

  derived from bacteria {or Archaea} · CPC title

• A61K47/6849

  the antibody targeting a receptor, a cell surface antigen or a cell surface determinant · CPC title

• C07K2319/90

  containing a motif for post-translational modification · CPC title

• C07K16/468

  Immunoglobulins having two or more different antigen binding sites, e.g. multifunctional antibodies · CPC title

• C07K16/44

  against material not provided for elsewhere {, e.g. haptens, metals, DNA, RNA, amino acids} · CPC title