IP Library Granted Patent US 9,701,728
Granted Patent B2
US 9,701,728 · App. 14/808,828 · Granted Jul 11, 2017

Methods and compositions for delivering interleukin-1 receptor antagonist

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Quick Facts
Patent No.
US 9,701,728
App. No.
14/808,828
Granted
Jul 11, 2017
Kind
B2
Abstract

Methods and compositions generating and using an interleukin-1 receptor antagonist (IL-1ra)-rich solution. Methods for generating and isolating interleukin-1 receptor antagonist include incubating a liquid volume of white blood cells and platelets with polyacrylamide beads to produce interleukin-1 receptor antagonist. The interleukin-1 receptor antagonist is isolated from the polyacrylamide beads to obtain the solution rich in interleukin-1 receptor antagonist. Methods for treating a site of inflammation in a patient include administering to the site of inflammation the solution rich in interleukin-1 receptor antagonist.

Claims (26)

1. A method of treating inflammation in a subject, comprising:

contacting a liquid volume comprising white blood cells with polyacrylamide beads, the white blood cells at a concentration at least equal to a concentration of white blood cells in whole blood;

separating the polyacrylamide beads from the liquid volume to obtain a composition comprising interleukin 1 receptor antagonist (IL-1ra); and

administering the composition to the subject.

2. The method of claim 1 , wherein the liquid volume comprises whole blood, a white blood cell fraction, a buffy coat fraction, a white blood cell isolate, platelet-rich plasma, or a combination thereof.

3. The method of claim 1 , wherein contacting comprises incubating the liquid volume with the polyacrylamide beads for a time from about 30 seconds to about 24 hours.

4. The method claim 1 , wherein the concentration of IL-1ra is at least 10,000 pg/ml.

5. A method of treating inflammation in a subject, comprising activating a liquid volume comprising white blood cells using a porous material to generate a composition comprising at least 10,000 pg/ml interleukin-1 receptor antagonist (IL-1ra), wherein the liquid volume has a concentration of white blood cells greater than a concentration of white blood cells in whole blood; and administering the composition to a site of inflammation in the subject.

6. The method of claim 5 , wherein the porous material comprises absorptive beads.

7. The method of claim 5 , wherein administering includes mixing the composition with fibrinogen, thrombin, calcium, an antibiotic, or a combination thereof, and applying the mixture to the site of inflammation.

8. The method of claim 5 , wherein activating includes allowing the porous material to absorb a fluid of the liquid volume.

9. The method of claim 5 , wherein the composition further comprises at least one protein selected from soluble tumor necrosis factor receptor-I, platelet-derived growth factor-AB, transforming growth factor β1, insulin-like growth factor-1, basic fibroblast growth factor, or vascular endothelial growth factor, wherein the selected protein is at a concentration greater than a concentration of the selected protein in whole blood.

10. A method of treating inflammation in a subject, comprising;

providing a liquid volume comprising white blood cells at a concentration greater than a concentration of white blood cells in whole blood;

concentrating the liquid volume to produce a composition having a concentration of interleukin-1 receptor antagonist (IL-1ra) of at least 10,000 pg/ml, including removing a portion of a fluid from the liquid volume; and

administering the composition to a site of inflammation in the subject.

11. The method of claim 10 , wherein the white blood cells are isolated from a volume of whole blood, Of comprise a fraction of whole blood, a buffy coat fraction, platelet-rich plasma, or a combination thereof.

12. The method of claim 10 , wherein concentrating includes mixing the liquid volume with an absorptive material.

13. The method of claim 10 , wherein concentrating includes mixing the liquid volume with polyacrylamide beads.

14. The method of claim 10 , wherein the liquid volume has a concentration of white blood cells of at least about 24,000/μL.

15. The method of claim 10 , wherein the composition comprises at least about 20,000 pg/ml IL-1ra.

16. The method of claim 10 , wherein the composition comprises at least about 30,000 pg/ml IL-1ra.

17. The method of claim 10 , wherein concentrating includes removing at least about 50% of the fluid.

18. The method of claim 10 , wherein the composition further comprises at least one protein selected from soluble tumor necrosis factor receptor-I, platelet-derived growth factor-AB, transforming growth factor β1, insulin-like growth factor-1, basic fibroblast growth factor, or vascular endothelial growth factor, wherein the selected protein has a concentration greater than a concentration of the selected protein in the whole blood or plasma of the subject.

19. The method of claim 10 , wherein the composition comprises white blood cells, platelets, or both, of the subject.

20. The method of claim 10 , further comprising administering to the site of inflammation an antibiotic, fibrinogen, thrombin, calcium from a source other than the composition, or a combination thereof.

Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 12, 2018
From: BIOMET BIOLOGICS, LLC
To: BIOMET, INC.
Reel/Frame 045914/0262 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 12, 2018
From: ZB MANUFACTURING, LLC
To: BIOMET MANUFACTURING, LLC
Reel/Frame 045914/0335 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 12, 2018
From: BIOMET, INC.
To: ZB MANUFACTURING, LLC
Reel/Frame 045914/0350 →