TREATING INFLAMMATORY CONDITIONS

• US 20110224645A1
• Filed: 09/10/2009
• Published: 09/15/2011
• Est. Priority Date: 09/10/2008
• Status: Active Grant

• Current Assignee: Tla Targeted Immunotherapies AB
• Original Assignee: Ith Immune Therapy Holdings AB
• Inventors: Cotton, Graham, Winqvist, Ola
• Granted Patent: US 8,877,177 B2
• Time in Patent Office: Days
• US Class Current: 604/500
• CPC Class Codes: A61M 1/3618 Magnetic separation
• CPC Class Codes: A61M 1/3679 by absorption A61M1/3675 takes precedence
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: B01J 20/262 obtained otherwise than by reactions only involving carbon to carbon unsaturated bonds, e.g. obtained by polycondensation macromolecular compounds obtained otherwise than by reactions only involving unsaturated carbon-to-carbon bonds per se C08G
• CPC Class Codes: B01J 20/267 Cross-linked polymers
• CPC Class Codes: B01J 20/28004 Sorbent size or size distribution, e.g. particle size
• CPC Class Codes: B01J 20/28009 Magnetic properties
• CPC Class Codes: B01J 20/28016 Particle form
• CPC Class Codes: B01J 20/3085 Chemical treatments not covered by groups B01J20/3007 - B01J20/3078
• CPC Class Codes: B01J 20/3212 consisting of a polymer obtained by reactions otherwise than involving only carbon to carbon unsaturated bonds
• CPC Class Codes: B01J 20/3219 involving a particular spacer or linking group, e.g. for attaching an active group
• CPC Class Codes: B01J 20/3242 Layers with a functional group, e.g. an affinity material, a ligand, a reactant or a complexing group
• CPC Class Codes: B01J 20/3272 Polymers obtained by reactions otherwise than involving only carbon to carbon unsaturated bonds
• CPC Class Codes: B01J 20/3274 Proteins, nucleic acids, polysaccharides, antibodies or antigens
• CPC Class Codes: B01J 2220/58 Use in a single column
• CPC Class Codes: C07K 14/52 Cytokines; Lymphokines; Interferons
• CPC Class Codes: C07K 14/521 Chemokines
• CPC Class Codes: C07K 17/06 attached to the carrier via a bridging agent
• CPC Class Codes: C07K 17/10 : the carrier being a carbohydrate

Abstract

An apheresis column loaded with a solid support comprises one or more chemokines, in particular biotinylated chemokines, immobilized directly or indirectly on the support, in particular on a support carrying streptavidin. Also disclosed are uses of the column and the support and a method of depleting cells, in particular leukocytes, from the peripheral blood of a person suffering from an inflammatory condition such as Inflammatory Bowel Disease (IBD).

Claims

1. An apheresis column loaded with a solid support comprising one or more chemokines immobilized directly or indirectly on the support to permit removal of a cell expressing the cognate receptor of the one or more chemokines from the peripheral blood of a patient.

2. The column of claim 1, wherein said one or more chemokines are biotinylated and wherein the support comprises streptavidin immobilized thereon and wherein the one or more biotinylated chemokines are bound to the streptavidin on the support.

5. The column of claim 1, wherein the support comprises or consists of a carbohydrate having a molecular weight of more than 100 kDa, optionally cross-linked.

7. The column of claim 1, wherein said one or more chemokines is selected from CCL25, MIP-Ia, MIP-Ib, MCP-I, MCP-2, MCP-3, MCP-4, TARC, MDC, MIP-3, MIP-3a, MIP3b, MIP-4, 1-309, HCC-I, HCC-2, SLC, IL-8, GROa, GROb, GROg, RANTES, NAP-2, ENA78, GCP-2, MG, I-TAC, SDF, fractalkine, lymphotactin, eotaxin, eotaxin-2, 1-309, and BLC.

8. The column of claim 7, wherein said one or more chemokines is CCL25.

9. The column of claim 7, wherein the support is in the form of spheres, beads or particles of irregular form having an average size from 50 μ

m to 2 mm.

10. The column of claim 1, wherein the support has been treated with an agent to provide it with anti-coagulation properties, such as a heparinized support.

3-4. -4. (canceled)

6. (canceled)

11. (canceled)

12. A method of removing a cell expressing a cognate receptor of one or more chemokines from the peripheral blood of a patient, comprising:

a. contacting collected peripheral blood with one or more chemokines immobilized on a solid support for a period of time sufficient to make said cell adhere to the support; and

b. separating the blood depleted in regard of said cell from the support.

14. The method of claim 12 further comprising, following step b, infusing the depleted blood to the patient.

15. The method of claim 12 wherein the cell is a leukocyte.

16. The method of claim 15 wherein the leukocyte is selected from a T lymphocyte, monocyte, neutrophil granulocyte or eosinophil granulocyte.

17. The method of claim 12 which is used to treat an inflammatory condition.

20. The method of claim 12, wherein said one or more chemokines are biotinylated and wherein the support comprises streptavidin immobilized thereon and wherein the one or more biotinylated chemokines are bound to the streptavidin on the support.

23. The method of claim 12, wherein said one or more chemokine is selected from CMS, MIP-Ia, MIP-Ib, MCP-I, MCP-2, MCP-3, MCP-4, TARC, MDC, MIP3, MIP-3a, MIP3b, MIP-4, 1-309, HCC-I, HICC-2, SLC, IL-8, GROa, GROb, GROg, RANTES, NAP-2, ENA78, GCP-2, IP-40, MIG, I-TAC, SDF, fractalkine, lymphotactin, eotaxin, eotaxin-2, 1-309, and BLC.

24. The method of claim 23, wherein said one or more chemokines is CCL25.

25. The method of claim 12, wherein the peripheral blood is continuously collected from the patient and the depleted blood is continuously infused to the patient.

28. The method of claim 12, wherein the support has been treated with an agent to provide it with anti-coagulation properties, such as a heparinized support and/or the peripheral blood has been treated with an anti-coagulant.

13. (canceled)

18-19. -19. (canceled)

21-22. -22. (canceled)

26-27. -27. (canceled)

29-35. -35. (canceled)

36. A truncated CCL25 chemokine comprising the amino acid sequence set forth as SEQ ID NO:

1 and which is biotinylated at position 72 (lysine) in order to permit immobilization of the chemokine on a solid support.

37. The chemokine of claim 36 further comprising a PEG spacer between the biotin and the lysine residue.