ENGRAFTMENT OF STEM CELLS WITH A COMBINATION OF AN AGENT THAT TARGETS STEM CELLS AND MODULATION OF IMMUNOREGULATORY SIGNALING

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(11)

EP 3 656 869 A8

(12)	CORRECTED EUROPEAN PATENT APPLICATION
	Note: Bibliography reflects the latest situation

(15)	Correction information:
	Corrected version no 1 (W1 A1)

(48)	Corrigendum issued on:
	10.06.2020 Bulletin 2020/24

(43)	Date of publication:
	27.05.2020 Bulletin 2020/22

(21)	Application number: 19198976.3

(22)	Date of filing: 26.08.2015

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International Patent Classification (IPC):

A61K 39/395^(2006.01)
A61K 38/17^(2006.01)
C07K 16/30^(2006.01)

A61K 35/28^(2015.01)
C12Q 1/68^(2018.01)
A61P 37/06^(2006.01)

(84)	Designated Contracting States:
	AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR

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Priority:

26.08.2014 US 201462041989 P

(62)	Application number of the earlier application in accordance with Art. 76 EPC:
	15835482.9 / 3186395

(71)	Applicant: The Board of Trustees of the Leland Stanford Junior University
	Stanford, CA 94305-2038 (US)

(72)	Inventors:
	SHIZURU, Judith, A. Palo Alto, CA California 94301 (US) WEISKOPF, Kipp Andrew Menlo Park, CA California 94025 (US) RING, Aaron Michael New Haven, CT 06511 (US) CHHABRA, Akanksha San Francisco, CA California 94117 (US) SCHNORR, Peter Sudbury, MA Massachusetts 01776 (US) WEISSMAN, Irving L. Stanford, CA California 94305 (US)

(74)	Representative: Chapman, Desmond Mark
	Carpmaels & Ransford LLP One Southampton Row London WC1B 5HA London WC1B 5HA (GB)


	Remarks:
	This application was filed on 23.09.2019 as a divisional application to the application mentioned under INID code 62.


	Remarks:
	Claims filed after the date of receipt of the application (Rule 68(4) EPC).

(54)	ENGRAFTMENT OF STEM CELLS WITH A COMBINATION OF AN AGENT THAT TARGETS STEM CELLS AND MODULATION OF IMMUNOREGULATORY SIGNALING

(57) The present invention provides a clinically applicable method of stem cell transplantation that facilitates engraftment and reconstitutes immunocompetence of the recipient without requiring radiotherapy or chemotherapy, and without development of GVHD or graft rejection. Aspects of the present invention are based on the discovery that the depletion of the endogenous stem cell niche facilitates efficient engraftment of stem cells into that niche. In particular, the present invention combines the use of selective ablation of endogenous stem cells with a combination of antibodies specific for CD117, and agents that modulate immunoregulatory signaling pathways, e.g. agonists of immune costimulatory molecules, in combination with the administration to the recipient of exogenous stem cells, resulting in efficient, long-term engraftment, even in immunocompetent recipients.