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1. (WO2019002456) PROCÉDÉS D’IDENTIFICATION D’AGENTS QUI INDUISENT UNE (RE)DIFFÉRENCIATION DANS DES CELLULES DE TUMEUR SOLIDE NON DIFFÉRENCIÉES OU DÉDIFFÉRENCIÉES



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INTERNATIONAL SEARCH REPORT (ISR)
Part 1:  1  2  3  4  5  6          Part 2:  A  B  C  D  E 
International application No. Applicant's or agent's file reference
PCT/EP2018/067397 181564WO EBO
International filing date (day/month/year) (Earliest) Priority Date (day/month/year)
28 June 2018 29 June 2017
Applicant
ESSER, Knud
FOR FURTHER ACTION: See Form PCT/ISA/220 as well as, where applicable, item 5 below.
This international search report has been prepared by this International Searching Authority and is transmitted to the applicant according to Article 18. A copy is being transmitted to the International Bureau.
It is also accompanied by a copy of each prior art document cited in this report.
1. Basis of the report
a. With regard to the language, the international search was carried out on the basis of:
the international application in the language in which it was filed.
a translation of the international application into                                          which is the language of a translation furnished for the purposes of international search (Rules 12.3(a) and 23.1(b)).
b.
This international search report has been established taking into account the rectification of an obvious mistake authorized by or notified to this Authority under Rule 91 (Rule 43.6bis(a)).
c.
With regard to any nucleotide and/or amino acid sequence disclosed in the international application, the international search was carried out on the basis of a sequence listing:
2. Certain claims were found unsearchable
3. Unity of invention is lacking
This International Searching Authority found multiple inventions in this international application, as follows:
1. claims: 1-18
Method for the identification of compounds inducing (re-)differentiation in non- or dedifferentiated cells, comprising:a) provision of a cell culture sample consisting of de-/ or undifferentiated tumour cells,b) bringing the compound of interest into contact with the cell culture sample,c) following the determination of the relative concentration of a first marker lactate in contrast to untreated cells, andd) following the determination of the relative concentration of a second marker neutral lipids in contrast to untreated cells,wherein steps c) and d) may be performed in reverse order if necessary
2. claim: 19
Vessel for the removal of liquids from cells via centrifugation characterized by comprising:- 4 side walls (ai, a2 , bi, b2 ), where the two opposing side walls have the same length (la , lb ), so that a rectangular shape is obtained,- a flat bottom (c) being connected in such a way with each of the side walls over all of the connecting area in a liquid proof way,- each of the side walls having a protrusion (da , db ) directed towards the inside of the vessel,- 2 of the 4 side walls being opposite to each other having recesses (ei, e2 ) positioned in the middle of the lengths la of the side wall on the upper surface of the respective side wall.
3. claims: 20, 21
Microtiter plate for culturing cells enabling addition of liquid via centrifugation, said plate comprising a surface (1) and wells (2), said wells being tapered towards the bottom (3) where an opening, especially a circular opening, is present.
1.
As all required additional search fees were timely paid by the applicant, this international search report covers all searchable claims.
2.
As all searchable claims could be searched without effort justifying additional fees, this Authority did not invite payment of additional fees.
3.
As only some of the required additional search fees were timely paid by the applicant, this international search report covers only those claims for which fees were paid, specifically claims Nos.:
4.
No required additional search fees were timely paid by the applicant. Consequently, this international search report is restricted to the invention first mentioned in the claims; it is covered by claims Nos.: 1-18
Remark on Protest
The additional search fees were accompanied by the applicant’s protest and, where applicable, the payment of a protest fee.
The additional search fees were accompanied by the applicant’s protest but the applicable protest fee was not paid within the time limit specified in the invitation.
No protest accompanied the payment of additional search fees.
4. Title of the invention
The text is approved as submitted by the applicant.
The text has been established by this Authority to read as follows:
METHODS FOR IDENTIFYING AGENTS WHICH INDUCE (RE) DIFFERENTIATION IN UN- OR DEDIFFERENTIATED SOLID TUMOR CELLS

5. Abstract
The text is approved as submitted by the applicant.
The text has been established, according to Rule 38.2, by this Authority as it appears in Box No. IV. The applicant may, within one month from the date of mailing of this international search report, submit comments to this Authority.
6. Drawings
a.
The figure of the drawings to be published with the abstract is Figure No.     1    
as suggested by the applicant.
as selected by this Authority, because the applicant failed to suggest a figure.
as selected by this Authority, because this figure better characterizes the invention.
b.
none of the figures is to be published with the abstract.

A. CLASSIFICATION OF SUBJECT MATTER

     G01N 33/50 (2006.01)i
According to International Patent Classification (IPC) or to both national classification and IPC

B. FIELDS SEARCHED

Minimum documentation searched (classification system followed by classification symbols):
     G01N
Documentation searched other than minimum documentation to the extent that such documents are included in the fields searched:
Electronic data base consulted during the international search (name of data base and, where practicable, search terms used):
EPO-Internal, BIOSIS, EMBASE, WPI Data

C. DOCUMENTS CONSIDERED TO BE RELEVANT

Category* Citation of document, with indication, where appropriate, of the relevant passages Relevant to claim No.
(1)
Y
HENRY WU ET AL, "Reduction in lactate accumulation correlates with differentiation-induced terminal cell division of leukemia cells*", DIFFERENTIATION.,Vol. 48, No. 1, 01 September 1991 (1991-09-01), page 51-58,
XP055456961
1-18
the whole document
(2)
Y
JEAN-MARC BLOUIN ET AL, "Butyrate elicits a metabolic switch in human colon cancer cells by targeting the pyruvate dehydrogenase complex", INTERNATIONAL JOURNAL OF CANCER,Vol. 128, No. 11, 08 October 2010 (2010-10-08), page 2591-2601,
XP055456743
1-18
figure 3d
(3)
Y
SANDRA VARUM ET AL, "Energy Metabolism in Human Pluripotent Stem Cells and Their Differentiated Counterparts", PLOS ONE,Vol. 6, No. 6, 17 June 2011 (2011-06-17), page e20914,
XP055457404
1-18
figure 3G
(4)
Y
HOFMANOVÁ JIRINA ET AL, "Lipid alterations in human colon epithelial cells induced to differentiation and/or apoptosis by butyrate and polyunsaturated fatty acids", THE JOURNAL OF NUTRITIONAL BIOCHEMISTRY,Vol. 23, No. 6, 2012, page 539-548,
XP028918963
1-18
Punkt 3.5;page 541
(5)
Y
HUI YAN ET AL, "Mechanism of Butyrate Stimulation of Triglyceride Storage and Adipokine Expression during Adipogenic Differentiation of Porcine Stromovascular Cells", PLOS ONE,Vol. 10, No. 12, 29 December 2015 (2015-12-29), page e0145940,
XP055456747
1-18
page 14, paragraph 1 - page 15, paragraph 1; figure 10
(6)
Y
VALÉRIE MARCIL ET AL, "Modulation of lipid synthesis, apolipoprotein biogenesis, and lipoprotein assembly by butyrate", AMERICAN JOURNAL OF PHYSIOLOGY - GASTROINTESTINAL AND LIVER PHYSIOLOGY,Vol. 283, No. 2, 01 August 2002 (2002-08-01), page G340-G346,
XP055457302
1-18
the whole document
(7)
Y
NÍVEA DIAS AMOÊDO ET AL, "Energy Metabolism in H460 Lung Cancer Cells: Effects of Histone Deacetylase Inhibitors", PLOS ONE,Vol. 6, No. 7, 18 July 2011 (2011-07-18), page e22264,
XP055457420
1-18
page 4, right-hand column, paragraph 2 - page 6, left-hand column, paragraph 1
(8)
Y
AJANTA CHAKRABORTY ET AL, "Long term induction by pterostilbene results in autophagy and cellular differentiation in MCF-7 cells via ROS dependent pathway", 10 January 2012 (2012-01-10), Vol. 355, No. 1, page 25-40,
XP028475246
[retrieved on  2012-01-16]
1-18
page 31, right-hand column, paragraph 1
(9)
Y
PUNJ V ET AL, "EFFECT OF VITAMIN D ANALOG (1ALPHA HYDROXY D5) IMMUNOCONJUGATED TO HER-2 ANTIBODY ON BREAST CANCER", INTERNATIONAL JOURNAL OF CA, JOHN WILEY & SONS, INC, US,Vol. 108, 01 January 2004 (2004-01-01), page 922-929,
XP008047279
1-18
page 922, right-hand column, paragraph 3
(10)
A
A. BELFIORE ET AL, "Insulin receptor and cancer", ENDOCRINE - RELATED CANCER,Vol. 18, No. 4, 23 May 2011 (2011-05-23), page R125-R147,
XP055422259
1-18
the whole document
(11)
A
SARAH F. ANDRES ET AL, "Insulin receptor isoform switching in intestinal stem cells, progenitors, differentiated lineages and tumors: evidence that IR-B limits proliferation", JOURNAL OF CELL SCIENCE,Vol. 126, No. 24, 14 October 2013 (2013-10-14), page 5645-5656,
XP055497343
1-18
the whole document
(12)
A
J. HEATH, "Appearance of functional insulin receptors during the differentiation of embryonal carcinoma cells", THE JOURNAL OF CELL BIOLOGY : JCB,Vol. 91, No. 1, 01 October 1981 (1981-10-01), page 293-297,
XP055497344
1-18
the whole document
*
Special categories of cited documents:
"A"
document defining the general state of the art which is not considered to be of particular relevance
"E"
earlier application or patent but published on or after the international filing date
"L"
document which may throw doubts on priority claim(s) or which is cited to establish the publication date of another citation or other special reason (as specified)
"O"
document referring to an oral disclosure, use, exhibition or other means
"P"
document published prior to the international filing date but later than the priority date claimed
"T"
later document published after the international filing date or priority date and not in conflict with the application but cited to understand the principle or theory underlying the invention
"X"
document of particular relevance; the claimed invention cannot be considered novel or cannot be considered to involve an inventive step when the document is taken alone
"Y"
document of particular relevance; the claimed invention cannot be considered to involve an inventive step when the document is combined with one or more other such documents, such combination being obvious to a person skilled in the art
"&"
document member of the same patent family
Name and mailing address of the ISA/:
European Patent Office
P.B. 5818, Patentlaan 2, 2280 HV Rijswijk,
Netherlands
Telephone No. (+31-70)340-2040
Facsimile No. (+31-70)340-3016
Date of the actual completion of the international search:
06 August 2018
Date of mailing of the international search report:
05 October 2018
Authorized officer:
Wiesner, Martina
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