Chimeric inhibitor molecules of complement activation

Patent metadata

Field	Value
Publication number	US-10294286-B2
Application number	US-201715400412-A
Country	US
Kind code	B2
Filing date	Jan 6, 2017
Priority date	Mar 5, 2010
Publication date	May 21, 2019
Grant date	May 21, 2019

Abstract

The present invention relates to novel chimeric molecules of ficolin-associated polypeptides, such as fusion polypeptides for the use in the treatment of conditions associated with inflammation, apoptosis, autoimmunity, coagulation, thrombotic or coagulopathic related diseases. The present invention further relates to nucleic acid molecules encoding such fusion polypeptides, vectors and host cells used in the production of the fusion polypeptides.

First claim

The invention claimed is:

1. A chimeric molecule of a ficolin-associated polypeptide comprising:
a) a human ficolin-associated polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 1 or a variant thereof having at least 80% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1; and
b) an immunoglobulin molecule or part thereof.

2. The chimeric molecule according to claim 1 , wherein said ficolin-associated polypeptide comprises the amino acid sequence of residues 20-297 of SEQ NO:3, or a functional variant thereof having at least 80% sequence identity to the amino acid sequence of residues 20-297 of SEQ ID NO: 3.

3. The chimeric molecule according to claim 1 , wherein said ficolin-associated polypeptide comprises the amino acid sequence of residues 20-380 of SEQ NO:1 or a functional variant thereof having at least 80% sequence identity to the amino acid sequence of residues 20-380 of SEQ ID NO: 1.

4. The chimeric molecule according to claim 1 , wherein said ficolin-associated polypeptide is in homodimer form.

5. The chimeric molecule according to claim 1 , wherein said ficolin-associated polypeptide consist of the amino acid sequence of residues 20-380 of SEQ ID NO 1.

6. The chimeric molecule according to claim 1 , wherein said ficolin-associated polypeptide comprises the amino acid sequence of SEQ ID NO:4 or variants or immunologic fragments thereof having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 4.

7. The chimeric molecule according to claim 1 , wherein said ficolin-associated polypeptide and said immunoglobulin molecule or part thereof are directly or indirectly fused to each other in the form of a fusion protein.

8. A composition comprising the chimeric molecule as defined in claim 1 .

9. The chimeric molecule of claim 1 , wherein said immunoglobulin molecule or part thereof consists of the Fc component of human IgG1, IgG2, IgG3, or IgG4.

10. The chimeric molecule of claim 1 , wherein said chimeric molecule directly or indirectly modulate complement activation when administered to a subject compared to complement activation in an appropriate control subject.

Assignees

• Rigshospitalet
• Kobenhavns Univ
• Univ Syddansk
• Omeros Corp

Inventors

• Garred Peter
• Glue Tina Hummelshoj
• Skjodt Mikkel-Ole

Classifications

• A61P37/02

  Immunomodulators · CPC title

• A61P7/02

  Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors · 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

• C07K14/8121

  Serpins · CPC title

• C07K2319/70

  containing domain for protein-protein interaction · CPC title