Complexes of types of MHC class II that bind to collagen type II peptides and their use on diagnosis and treatment

Patent metadata

Field	Value
Publication number	US-10774129-B2
Application number	US-201514953484-A
Country	US
Kind code	B2
Filing date	Nov 30, 2015
Priority date	Apr 5, 2011
Publication date	Sep 15, 2020
Grant date	Sep 15, 2020

Abstract

Novel complexes of peptides from human collagen type II and types of MHC class II associated with rheumatoid arthritis are provided. There is also provided novel therapies and methods for diagnosis of rheumatoid arthritis.

First claim

I claim:

1. A complex of a human recombinant MHC class II protein fragment of HLA-DRB1 *1001 and the synthesized or recombinantly produced peptide consisting of SEQ ID NO 46, wherein said fragment of said human recombinant MEW class II protein excludes at least the transmembrane domains of said MEW class II protein and is stabilized by at least one of: retaining parts of the alpha 2 and beta 2 inner domains, introducing a leucine zipper structure to the inner domains, introducing cysteine residues that form disulfide bridges linking the alpha and the beta chains, and introducing a peptide in the peptide binding groove that is covalently linked to an elongation of the beta domain.

2. A kit of parts comprising the complex of claim 1 .

3. The kit according to claim 2 additionally comprising at least one cell culture vessel.

4. The kit according to claim 2 comprising means for detecting the expression of at least one protein selected from the group consisting of CD3, CD4, Foxp3, CD25, TNF alpha, interferon gamma, interleukin-17A, interleukin-17F, CD154, CD69, Ki 67, interleukin-2, interleukin-13 and interleukin-10.

5. The kit according to claim 4 where the means for detection is an antibody against said protein.

6. The kit according to claim 4 where the means for detection is a set of primers for RT-PCR.

7. A composition comprising the complex of claim 1 and an additive or excipient.

8. The complex of claim 1 , wherein said complex is stable in solution.

9. The complex of claim 8 , wherein said human recombinant WIC class II protein fragment excluding said transmembrane domains is stabilized by retaining parts of the alpha 2 and beta 2 inner domains.

10. The complex of claim 8 , wherein the inner domains of said human recombinant WIC class II protein fragment excluding said transmembrane domains are stabilized by the introduction of a leucine zipper structure.

11. The complex of claim 8 , wherein said human recombinant WIC class II protein fragment excluding said transmembrane domains is stabilized by introducing cysteine residues that form disulfide bridges linking the alpha and the beta chains.

12. The complex of claim 8 , wherein said human recombinant WIC class II protein fragment excluding said transmembrane domains is stabilized by introducing a peptide in the peptide binding groove that is covalently linked to an elongation of the beta domain.

Assignees

• Fraunhofer Ges Forschung

Inventors

• Holmdahl Rikard

Classifications

• A61K38/014

  from connective tissue peptides, e.g. gelatin, collagen · CPC title

• C12N9/88

  Lyases (4.) · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• C12Y402/01011

  Phosphopyruvate hydratase (4.2.1.11), i.e. enolase · CPC title

• A61K38/00

  Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) · CPC title