IP Library Granted Patent US 12,280,074
Granted Patent B2
US 12,280,074 · App. 16/087,471 · Granted Apr 22, 2025

Preparation of platelet pellet lysate and its use for treating neurological disorders

Inventors: David Devos (Lille, FR); Thierry Burnouf (Lille, FR); Jean-christophe Devedjian (Lille, FR); Ming-Li Chou (Taoyuan, TW)
Assignees: Centre Hospitalier Regional et Universitaire de Lille (CHRU); Universite de Lille; Universite du Littoral Cote D'Opale; Inserm (Institut National de La Sante et de la Recherche Medicale); Taipei Medical University
A61K35/19A61P25/16A61P25/28
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Quick Facts
Patent No.
US 12,280,074
App. No.
16/087,471
Granted
Apr 22, 2025
Kind
B2
Abstract

A process for preparing a modified heat-treated platelet pellet lysate, said process comprising the steps of: a) Providing a platelet pellet lysate, b) Heat-treating the platelet pellet lysate at a temperature of 55° C. to 65° C. during 20 to 40 minutes, c) Purifying the heat-treated platelet pellet lysate of step b) so as to obtain a modified heat treated platelet pellet lysate having a total protein content of less than 70% of the total protein content of the platelet pellet lysate of step a).

Claims (40)

1. A method for treating a neurological disorder selected from Parkinson's disease and amyotrophic lateral sclerosis, comprising a step of administering an effective amount of a platelet pellet lysate which is modified by a heat treatment at a temperature of 55° C. to 65° C. for 20 to 40 minutes to a patient in need thereof, said lysate having a total protein content of less than 70 % of the total protein content of non-heated platelet pellet lysate, wherein the platelet pellet lysate is prepared using a method comprising steps of:

i. providing a platelet concentrate from human blood;

ii. centrifuging the platelet concentrate to obtain a platelet pellet and a plasma supernatant;

iii. removing the plasma supernatant and suspending the platelet pellet;

iv. subjecting the suspended platelet pellet to freeze/thaw cycles to lyse platelets of the suspended platelet pellet and obtain a suspension; and

v. removing cell debris of the suspension obtained in step iv by centrifugation to obtain a platelet pellet lysate.

2. The method according to claim 1 , wherein the platelet pellet lysate is administered by intrathecal, intraocular, intranasal or intra cerebroventricular route.

3. The method of claim 1 , wherein said platelet pellet lysate is administered by intra cerebroventricular route.

4. The method of claim 1 , wherein said platelet pellet lysate is administered with a pump.

5. The method of claim 1 , wherein said platelet pellet lysate has a total protein content of less than 60% of the total protein content of non heat-treated platelet pellet lysate.

6. The method of claim 1 , wherein said platelet pellet lysate has a total protein content of less than 50% of the total protein content of non heat-treated platelet pellet lysate.

7. The method of claim 1 , wherein said platelet pellet lysate is administered into the right lateral ventricle.

8. The method of claim 1 , wherein said platelet pellet lysate is administered into the third ventricle.

9. A method for treating Parkinson's disease, comprising a step of administering an effective amount of a platelet pellet lysate which is modified by a heat treatment at a temperature of 55°° C. to 65° C. for 20 to 40 minutes to a patient in need thereof, said lysate having a total protein content of less than 70 % of the total protein content of non-heated platelet pellet lysate, wherein the platelet pellet lysate is prepared using a method comprising steps of:

i. providing a platelet concentrate from human blood;

ii. centrifuging the platelet concentrate to obtain a platelet pellet and a plasma supernatant;

iii. removing the plasma supernatant and suspending the platelet pellet;

iv. subjecting the suspended platelet pellet to freeze/thaw cycles to lyse platelets of the suspended platelet pellet and obtain a suspension; and

v. removing cell debris of the suspension obtained in step iv by centrifugation to obtain a platelet pellet lysate.

10. The method according to claim 9 , wherein the platelet pellet lysate is administered by intrathecal, intraocular, intranasal or intra cerebroventricular route.

11. The method of claim 9 , wherein said platelet pellet lysate has a total protein content of less than 60% of the total protein content of non heat-treated platelet pellet lysate.

12. The method of claim 9 , wherein said platelet pellet lysate has a total protein content of less than 50% of total protein content of non heat-treated platelet pellet lysate.

13. The method of claim 9 , wherein said platelet pellet lysate is administered into the right lateral ventricle.

14. The method of claim 9 , wherein said platelet pellet lysate is administered into the third ventricle.

15. A method for treating amyotrophic lateral sclerosis, comprising a step of administering an effective amount of a platelet pellet lysate which is modified by a heat treatment at a temperature of 55° C. to 65° C. for 20 to 40 minutes to a patient in need thereof, said lysate having a total protein content of less than 70% of the total protein content of non-heated platelet pellet lysate, wherein the platelet pellet lysate is prepared using a method comprising steps of:

i. providing a platelet concentrate from human blood;

ii. centrifuging the platelet concentrate to obtain a platelet pellet and a plasma supernatant;

iii. removing the plasma supernatant and suspending the platelet pellet;

iv. subjecting the suspended platelet pellet to freeze/thaw cycles to lyse platelets of the suspended platelet pellet and obtain a suspension; and

v. removing cell debris of the suspension obtained in step iv by centrifugation to obtain a platelet pellet lysate.

16. The method according to claim 15 , wherein the platelet pellet lysate is administered by intrathecal, intraocular, intranasal or intra cerebroventricular route.

17. The method of claim 15 , wherein said platelet pellet lysate has a total protein content of less than 60% of the total protein content of non heat-treated platelet pellet lysate.

18. The method of claim 15 , wherein said platelet pellet lysate has a total protein content of less than 50% of total protein content of non heat-treated platelet pellet lysate.

19. The method of claim 15 , wherein said platelet pellet lysate is administered into the right lateral ventricle.

20. The method of claim 15 , wherein said platelet pellet lysate is administered into the third ventricle.

21. The method according to claim 1 , wherein the platelet pellet lysate is modified by the heat treatment for 30 minutes.

22. The method according to claim 1 , wherein the platelet pellet lysate is modified by the heat treatment at 56° C.

23. The method according to claim 21 , wherein the platelet pellet lysate is modified by the heat treatment at 56° C.

24. The method according to claim 1 , wherein following the heat treatment the platelet pellet lysate is purified by centrifugation or filtration.

25. The method according to claim 23 , wherein following the heat treatment, the platelet pellet lysate is purified by centrifugation or filtration.

Assignments (2)
MERGER Recorded Sep 9, 2024
From: UNIVERSITE DE LILLE 2 DROIT ET SANTE
To: UNIVERSITÉ DE LILLE
Reel/Frame 068894/0039 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 10, 2023
From: DEVOS, DAVID; BURNOUF, THIERRY; DEVEDJIAN, JEAN-CHRISTOPHE; CHOU, MING-LI
To: CENTRE HOSPITALIER REGIONAL ET UNIVERSITAIRE DE LILLE (CHRU); UNIVERSITE DE LILLE 2 DROIT ET SANTE; UNIVERSITE DU LITTORAL COTE D'OPALE; INSERM ( INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE); TAIPEI MEDICAL UNIVERSITY
Reel/Frame 065528/0866 →
Priority Claims (1)
EP 16305332 · Mar 23, 2016 · regional
Continuity (1)
Related Publication 20190099448A1 · Apr 4, 2019
References Cited (52)
US 11744863B2 · Devos et al. · 2023 [cited by examiner]
US 20070265203A1 · Eriksson et al. · 2007 [cited by examiner]
WO WO2009155069A1 · 2009 [cited by examiner]
Choi et al. “Effect of platelet lysate on growth and sulfated glycosaminoglycan synthesis in articular chondrocyte cultures”, Arthritis & Rheumatism, vol. 23, No. 2, 1980, pp. 220-224, (Year: 1980). [cited by examiner]
Hayon et al. “Platelet lysates stimulate angiogenesis, neurogenesis and neuroprotection after stroke” Thromb Haemost 2013, 110: 323-330. (Year: 2013). [cited by examiner]
Chou et al. “Ex vivo Expansion of Bovine Corneal Endothelial Cells in Xeno-Free Medium Supplemented with Platelet Releasate” PLOS ONE 2014, 9(6): e99145, 8 pages. (Year: 2014). [cited by examiner]
Anitua et al. “Intranasal Delivery of Plasma and Platelet Growth Factors Using PRGF-Endoret System Enhances Neurogenesis in a Mouse Model of Alzheimer's Disease” PLoS ONE 2013, 8(9): e73118, 13 pages. (Year: 2013). [cited by examiner]
Bonin et al. “Treatment of refractory acute GVHD with third-party MSC expanded in platelet lysate-containing medium” Bone Marrow Transplantation (2009) 43, 245-251. (Year: 2009). [cited by examiner]
Choi et al. (1980) “Effect of platelet lysate on growth and sulfated glycosaminoglycan synthesis in articular chondrocyte cultures” Arthritis and Rheumatism, vol. 22, No. 2, pp. 220-224. (Year: 1980). [cited by examiner]
Copland et al. (2013) “The effect of platelet lysate fibrinogen on the functionality of MSCs in immunotherapy” Biomaterials, 34(32), 7840-7850. (Year: 2013). [cited by examiner]
Chou et al. (2017) “Tailor-made purified human platelet lysate concentrated in neurotrophins for treatment of Parkinson's disease” Biomaterials, 142, 77-89. (Year: 2017). [cited by examiner]
The International Search Report and Written Opinion, mailed on May 9, 2017, in the related PCT Appl. No. PCT/EP2017/057004. [cited by applicant]
Choi et al: “Effect of platelet lysate on growth and sulfated glycosaminoglycan synthesis in articular chondrocyte cultures”, Arthritis & Rheumatism, vol. 23, No. 2, Jan. 1, 1980 (Jan. 1, 1980), pp. 220-224. [cited by applicant]
Tang et al.: “Survival effect ofPDGF-CC rescues neurons from apoptosis in both brain and retina by regulating GSK3 beta phosphorylation”, Journal of Experimental Medicine, vol. 207, 2010, pp. 867-880. [cited by applicant]
Hara et al. “Platelets as a Source of Growth-promoting Factor(s) for Tumor Cells”, Cancer Research, Apr. 1, 1980 (Apr. 1, 1980), pp. 1212-1216. [cited by applicant]
Aron et al., “Repairing the parkinsonian brain with neurotrophic factors,” Trends Neurosci 2011;34: 88-100. [cited by applicant]
Barrientos et al., “Growth factors and cytokines in wound healing,” Wound Repair Regen 2008;16: 585-601. [cited by applicant]
Blair et al., “Platelet alpha-granules: basic biology and clinical correlates,” Blood Rev 2009;23: 177-89. [cited by applicant]
Burnouf et al., “Nanofiltration of plasma bio-pharmaceutical products [invited review] . Haemophilia,” 2003, 9: 24-37. [cited by applicant]
Burnouf et al., Place of nanofiltration for assuring viral safety of biologicals. Current Nanoscience, 2005; 1: 189-201. [cited by applicant]
Burnouf et al., “Human platelet concentrates: a source of solvent/detergent-treated highly enriched brain-derived neurotrophic factor,” Transfusion 2012;52: 1721-8. [cited by applicant]
Burnouf et al., “A chromatographically purified human TGF-betaI fraction from virally inactivated platelet lysates,” Vox Sang 2011;101: 215-20. [cited by applicant]
Burnouf et al., “Antimicrobial activity of platelet (PLT)-poor plasma, PLT-rich plasma, PLT gel, and solvent/detergent-treated PLT lysate biomaterials against wound bacteria,” Transfusion 2013 ;53: 138-46. [cited by applicant]
Burnouf et al., “Blood-derived biomaterials and, platelet growth factors in regenerative medicine,” Blood Rev 2013;27: 77-89. [cited by applicant]
Falk et al., “Vascular endothelial growth factor-B is neuroprotective in an in vivo rat model of Parkinson's disease,” Neurosci Lett 2011;496: 43-7. [cited by applicant]
Gash et al., “Functional recovery in parkinsonian monkeys treated with GDNF,” Nature 1996;380: 252-5. [cited by applicant]
Gonzalez et al., “Antiparkinsonian trophic action of glial cell line-derived neurotrophic factor and transforming growth factor beta 1 is enhanced after co-infusion in rats,” Experimental Neurology 2010;226: 136-47. [cited by applicant]
Hayon et al., “Platelet lysates stimulate angiogenesis, neurogenesis and neuroprotection after stroke,” Thromb Haemost 2013;110: 323-30. [cited by applicant]
Hefti et al., “Function of neurotrophic factors in the adult and aging brain and their possible use in the treatment of neurodegenerative diseases,” Neurobiol Aging 1989;10:515-33. [cited by applicant]
Hoffer et al., “Glial cell line-derived neurotrophic factor reverses toxin-induced injury to midbrain dopaminergic neurons in vivo,” Neurosci Lett 1994;182: 107-11. [cited by applicant]
Huang et al., “Neurotrophins: roles in neuronal development and function,” Annu Rev Neurosci 2001;24: 677-736. [cited by applicant]
Kearns et al., “GDNF protects nigral dopamine neurons against 6-hydroxydopamine in vivo,” Brain Res 1995;672: 104-11. [cited by applicant]
Kirik et al., “Localized striatal delivery of GDNF as a treatment for Parkinson disease,” Nat Neurosci 2004;7: 105-10. [cited by applicant]
Klein HG, “Should blood be an essential medicine?” N Engl J Med 2013;368: 199-201. [cited by applicant]
Laloux et al., “MPTP-treated mice: long-lasting loss of nigral TH-ir neurons but not paradoxical sleep alterations,” Experimental Brain Research 2008;186: 635-42. [cited by applicant]
Mohapel et al., “Platelet-derived growth factor (PDGF-BB) and brain-derived neurotrophic factor (BDNF) induce striatal neurogenesis in adult rats with 6-hydroxydopamine lesions,” Neuroscience 2005;132: 767-76. [cited by applicant]
Nurden et al., “Platelets and wound healing,” Front Biosci 2008;13: 3532-48. [cited by applicant]
Nutt et al., “Randomized, double-blind trial of glial cell line-derived neurotrophic factor (GDNF) in PD,” Neurology 2003;60: 69-73. [cited by applicant]
Rodrigues et al., “Challenges and Promises in the Development of Neurotrophic Factor-Based Therapies for Parkinson's Disease,” Drugs & Aging 2014;31: 239-61. [cited by applicant]
Roussa et al, “TGF-beta in dopamine neuron development, maintenance and neuroprotection,” Adv Exp Med Biol 2009;651: 81-90. [cited by applicant]
Ruozi et al., “Neurotrophic factors and neurodegenerative diseases: a delivery issue,” Int. Rev. Neurobiol 2012;102: 207-47. [cited by applicant]
Ryu et al., “Fibrinogen signal transduction in the nervous system. Journal of thrombosis and heamostasis,” 2009; vol. 7, issue supplement si, 151-154. [cited by applicant]
Santo et al., “Chitosan-chondrotin sulphate nanoparticles for controlled delivery of platelet lysates in bone regenerative medicine. Journal of Tissue Engineering and Regenerative Medicine,” Dec. 2012, vol. 6, issue S3,… [cited by applicant]
Schabitz et al., “Intravenous brain-derived neurotrophic factor enhances poststroke sensorimotor recovery and stimulates neurogenesis,” Stroke 2007;38:2165-72. [cited by applicant]
Scholz et al., “Rapid, complete and large-scale generation of post-mitotic neurons from the human LUHMES cell line,” J Neurochem 2011;119: 957-71. [cited by applicant]
Su et al., “Quantitative assessment of the kinetics of growth factors release from platelet gel,” Transfusion 2008;48: 2414-20. [cited by applicant]
Su CY, Kuo YP, Lin YC, et al. A virally inactivated functional growth factor preparation from human platelet concentrates. Vox Sang 2009;97: 119-28. [cited by applicant]
Timmer et al., “Fibroblast growth factor (FGF)-2 and FGF receptor 3 are required for the development of the substantia nigra, and FGF-2 plays a crucial role for the rescue of dopaminergic neurons after 6-hydroxydopamine… [cited by applicant]
Tomac et al., “Protection and repair of the nigrostriatal dopaminergic system by GDNF in vivo,” Nature 1995;373: 335-9. [cited by applicant]
Burnouf et al., “Human platelet lysate: replacing fetal bovine serum as a gold standard for human cell propagation?” Biomaterials;76: 371-87, Jan. 2016. [cited by applicant]
Golebiewska et al., “Platelet secretion: From haemostasis to wound healing and beyond,” Blood Rev;29: 153-62, May 2015. [cited by applicant]
Shih et al., “Preparation, quality criteria, and properties of human blood platelet lysate supplements for ex vivo stem cell expansion,” New Biotechnology, vol. 32, Issue 1, pp. 199-211, Jan. 25, 2015. [cited by applicant]