Microbiome Response To Agents

The text shown here has been derived from the original document's published images via a process of ´optical character recognition (OCR). Due to variations in image quality, and the imperfect nature of OCR process, this text may not be 100% accurate. To view the original published images, please refer to the PDF.


(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT)
(19) World Intellectual Property

Organization
International Bureau

(10) International Publication Number

(43) International Publication Date
5 November 2015 (05.11.2015)

P O

PCT

(51) International Patent Classification:
C12Q 1/02 (2006.0 1)
C12Q 1/04 (2006.0 1)
A61B 5/00 (2006.01)
C12Q 1/68 (2006.01)
A61K 35/66 (2015.01)
G01N 33/68 (2006.01)
A61K 35/741 (2015.01)
(21) International Application Number:
PCT/IL20 15/050442

(22) International Filing Date:
28 April 2015 (28.04.2015)

(25) Filing Language:

English

WO 2015/166492 A3

(81) Designated States (unless otherwise indicated, for every
kind of national protection available): AE, AG, AL, AM,
AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY,
BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM,
DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT,
HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR,
KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG,
MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM,
PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC,
SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN,
TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW.

(84) Designated States (unless otherwise indicated, for every
kind of regional protection available): ARIPO (BW, GH,
GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ,
(30) Priority Data:
TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU,
61/984,944
28 April 2014 (28.04.2014)
US
TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE,
62/048,065
9 September 2014 (09.09.2014)
US
DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU,
62/050,939 16 September 2014 (16.09.2014)
US
LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK,
(71) Applicant: YEDA RESEARCH AND DEVELOPMENT
SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ,
CO. LTD. [IL/IL]; at the Weizmann Institute of Science,
GW, KM, ML, MR, NE, SN, TD, TG).
P.O. Box 95, 7610002 Rehovot (IL).
Declarations under Rule 4.17 :
(72) Inventors: ELINAV, Eran; 16 HaGefen Street, 7680400
—
of inventorship (Rule 4. 1 7(iv))
Mazkeret Batia (IL). SEGAL, Eran; 40 Nachshon Street,
4730168 Ramat-HaSharon (IL).
Published:
(26) Publication Language:

English

(74) Agents: G. E. EHRLICH (1995) LTD. et al; 11 Menachem Begin Road, 5268 104 Ramat Gan (IL).

—

with international search report (Art. 21(3))

[Continued on next page]
(54) Title: MICROBIOME RESPONSE TO AGENTS

(57) Abstract: A method of determining tolerance
to an agent in a healthy subject is disclosed. The
method comprises: (a) determining a signature of a
microbiome in a sample of the healthy subject who
has been subjected to the agent or condition; and
(b) comparing the signature of the microbiome of
the healthy subject to at least one reference signa
ture of a pathological microbiome, wherein when
the signature of the microbiome of the healthy sub
ject is statistically significantly similar to the refer
ence signature of the pathological microbiome, it is
indicative that the healthy subject is intolerant to
the agent.

<

o

o

before the expiration of the time limit for amending the
claims and to be republished in the event of receipt of
amendments (Rule 48.2(h))
with sequence listing part of description (Rule 5.2(a))

(88) Date of publication of the international search report:
23 December 2015

A . CLASSIFICATION

INV.

O F SUBJECT

MATTER

A61B5/00
G01N33/68

C12Q1/02
C12Q1/68

A61K35/66

A61K35/741

C12Q1/04

ADD.
According

to International

Patent Classification

(IPC) o r t o both national classification

and IPC

B . FIELDS SEARCHED
Minimum documentation

G06F

C12Q

Documentation

Electronic

searched

searched

C . DOCUMENTS
Category*

system followed

during the international

WPI

CONSIDERED

Citation of document,

by classification

symbols)

G01N

other than minimum documentation

data base consulted

EPO-Internal ,

(classification

A61K

A61B

to the extent that such documents

are included

search (name of data base and, where practicable,

Data, BIOSIS,

COMPENDEX,

in the fields searched

search terms used)

FSTA, INSPEC

EMBASE,

T O B E RELEVANT
with indication,

where appropriate,

of the relevant passages

Relevant to claim No.

A. N. PAYNE ET AL: "Gut mi crobi al
adaptati on t o di etary consumpti on of
fructose,
arti f i ci al sweeteners and sugar
al cohol s : impl i cati ons for host-mi crobe
i nteracti ons contri buti ng t o obesi ty" ,
OBESITY REVI EWS,
vol . 13 , no. 9 , 1 1 June 2012 (2012-06-11)

pages 799-809 , XP055205060,
ISSN : 1467-7881 , DOI :
10. 1111/J . 1467-789X. 2012 . 01009 . x
ci ted i n the appl i cati on
the whol e document
abstract
tabl e 3 on page 803
page 803 , l eft col umn , l ast paragraph
r i ght col umn , l ast paragraph
page 807 , l eft col umn

1-50

,

-

-/X|

Further documents

* Special categories

are listed in the continuation

of cited documents

of Box C .

:

"A" document defining the general state of the art which is not considered
to be of particular relevance
"E" earlier application
filing date

o r patent but published

o n o r after the international

"L" documentwhich
may throw doubts o n priority claim(s) orwhich is
cited to establish the publication date of another citation o r other
special reason (as specified)
"O" document
means

referring to a n oral disclosure,

use, exhibition

o r other

"P" document published prior to the international
the priority date claimed

filing date but later than

Date of the actual completion

search

of the international

"T" later document published after the international filing date o r priority
date and not in conflict with the application but cited to understand
the principle o r theory underlying the invention
"X" document of particular relevance; the claimed invention cannot be
considered novel o r cannot b e considered to involve a n inventive
step when the document is taken alone
"Y" document of particular relevance; the claimed invention cannot be
considered to involve a n inventive step when the document is
combined with one o r more other such documents, such combination
being obvious to a person skilled in the art
"&" document

search report

20/10/2015

of the ISA/

European Patent Office, P.B. 5818 Patentlaan
N L - 2280 HV Rijswijk
Tel. (+31-70) 340-2040,
Fax: (+31-70) 340-3016

member of the same patent family

Date of mailing of the international

10 August 2015
Name and mailing address

See patent family annex.

Authorized

officer

2

Gal 1-Truchot,

A

C(Continuation).
Category*

X

DOCUMENTS CONSIDERED TO BE RELEVANT

Citation of document, with indication, where appropriate, of the relevant passages

THERESA E COWAN ET AL:

"Arti f i c i a l
sweetener consumpti on d i fferenti
al l y
affects
the gut mi crobi ota-host
metabol i c
i nteracti
ons - - Cowan et a l . 27 (1) : 224. 7
- - The FASEB Journal " ,

Relevant to claim No.

1 , 5 ,6,
8-14, 19 ,
22 ,24,
25 ,27 ,
39 ,44,45

THE FASEB JOURNAL,

vol . 27 , 1 Apri l 2013 (2013-04-01)
224. 7 , XP055205066,
ISSN : 0892-6638
c i ted i n the appl i cati on
the whol e document
Y

, page

2010/172874 Al (TURNBAUGH PETER J [US]
8 July 2010 (2010-07-08)
c i ted i n the appl i cati on
the whol e document
abstract
c l aims 18, 23
page 19 , paragraph
94 - page 20, paragraph
99
exampl e 2 , pages 22-23
c l aim 2 1

20,21

TH0MPS0N-CHAG0YAN 0 C ET AL:
" Faecal
mi crobi ota and short-chai
n fatty
aci d

1 ,6,7 ,
1 1 , 12 ,
14-18,
24-26,
39-45

US

ET AL)

X

l evel s i n faeces

from

i nfants

wi t h cow ' s

mi l k protei n a l l ergy" ,
INTERNATIONAL ARCHIVES OF ALLERGY AND
IMMUNOLOGY, KARGER AG, CH ,

Y

vol . 156, no. 3 ,
1 January 2011 (2011-01-01)
, pages
325-332 , XP009166971 ,
ISSN : 1018-2438
the whol e document
abstract
sentence bri dgi ng pages 325-326
page 327 , l eft col umn , l ast paragraph
r i ght col umn , thi r d paragraph : " FISH of
bacteri a l cel l s "
page 327 , r i ght col umn , l ast paragraph :
"Determi nati on of Faecal SCFA"
page 328, r i ght col umn , paragraph
2
"Bacteri a l Counts ( FISH-FC) " and tabl e 3
on page 328
page 328, r i ght col umn , l ast paragraph
page 329 , r i ght col umn , l ast paragraph
and
tabl e 4 on page 330

-/--

20,21

C(Continuation).
Category*

X, P

X, P

DOCUMENTS CONSIDERED TO BE RELEVANT

Citation of document, with indication, where appropriate, of the relevant passages

AL:
"The rol e of
commensal bacteri a i n the regul ati on of
sensi t i zati on t o food a l l ergens" ,
FEBS LETTERS, ELSEVI ER, AMSTERDAM, NL,
vol . 588, no. 22 , 1 May 2014 (2014-05-01)
pages 4258-4266, XP029083055 ,
ISSN : 0014-5793 , D0I :
10. 1016/J . FEBSLET.2014.04.026
the whol e document

Relevant to claim No.

1 ,5-22 ,
24-27 ,
39-45

CAO SEVERINE ET

,

J0THAM SUEZ ET AL:

"Arti f i c i a l sweeteners
i nduce g l ucose i ntol erance by a l teri ng the
gut mi crobi ota" ,

1 ,5-22 ,
24-27 ,
39-45

NATURE,
17 September

2014 (2014-09-17) ,
XP055205484,
ISSN : 0028-0836,
D0I : 10. 1038/naturel3793
the whol e document
X, P

SUEZ J ET AL:

"Non-cal ori c arti f i c i a l
sweeteners and the mi crobi ome: Fi ndi ngs
and chal l enges" ,
GUT MICROBES 20150401 TAYLOR AND FRANCIS
INC. USA,
vol . 6 , no. 2 , 1 Apri l 2015 (2015-04-01) ,
pages 149-155 , XP008177160,
ISSN : 1949-0976,
D0I :
10. 1080/19490976.2015 . 1017700
the whol e document

1 ,5-22 ,
24-27 ,
39-45

X, P

MARI E S. A. PALMNAS ET AL:

1 , 5 ,6,
8-10, 13 ,
14,24,
25 ,39

" Low-Dose
Aspartame Consumpti on Di fferenti
al l y
Affects
Gut Mi crobi ota-Host
Metabol i c
Interacti
ons i n the Di et-Induced
Obese
Rat" ,
PL0S ONE,

vol . 9 , no. 10,
14 October 2014 (2014-10-14) , page
el09841 , XP055205532 ,
D0I : 10. 1371/journal
.pone. 0109841
the whol e document
X, P

THAISS CHRIST0PH A ET AL:
"Transki ngdom
Control
of Mi crobi ota Di urnal Osci l l ati ons
Promotes Metabol i c Homeostasi s " ,
CELL, CELL PRESS, US,
vol . 159 , no. 3 ,
16 October 2014 (2014-10-16) , pages
514-529 , XP029084863 ,
ISSN : 0092-8674,
D0I :
10. 1016/J . CELL.2014.09 .048
the whol e document

-/--

1, 5 , 7 ,
1 1 , 12 ,
14-21 ,
24-26,
39-45

C(Continuation).
Category*

DOCUMENTS CONSIDERED TO BE RELEVANT

Citation of document, with indication, where appropriate, of the relevant passages

THAISS C A ET AL:
" A day i n the l i f e of
the meta-organi sm: Di urnal rhythms of the
i ntesti nal mi crobi ome and i t s host" ,
GUT MICROBES 20150422 TAYLOR AND FRANCIS
INC. USA,
vol . 6 , no. 2 , 22 Apri l 2015 (2015-04-22) ,
pages 137-142 , XP008177161 ,
ISSN : 1949-0976,
D0I :
10. 1080/19490976.2015 . 1016690
the whol e document

Relevant to claim No.

I ,5,7,
I I , 12 ,
14-21 ,
24-26,
39-45

International

INTERNATIONAL SEARCH REPORT
Box No. II

search report has not been established

in respect o f certain claims under Article

(2) (a) for the following reasons:

Claims Nos.:
because they relate to subject matter not required to be searched by this Authority, namely:

23, 38
Claims Nos.:
because they relate to parts of the international application that d o not comply with the prescribed
an extent that n o meaningful international search can be carried out, specifically:
FURTHER INFORMATION

□

Claims Nos.:
because they are dependent

Box No. Ill

requirements

to such

sheet PCT/ISA/21Q

claims and are not drafted in accordance

with the second and third sentences of Rule 6.4(a).

Observations where unity of invention is lacking (Continuation of item 3 of first sheet)

This International

Searching Authority found multiple inventions

see addi tional

1. 1

No.

Observations where certain claims were found unsearchable (Continuation of item 2 of first sheet)

This international

□

application

PCT/I L2015/05Q442

in this international

application,

as follows:

sheet

As all required additional search fees were timely paid by the applicant, this international

search report covers all searchable

' claims.

2.

I I As all searchable

claims could be searched without effort justifying

a n additional fees, this Authority did not invite payment o f

additional fees.

'

As only some o f the required additional search fees were timely paid by the applicant, this international
' only those claims for which fees were paid, specifically claims Nos. :

I I No required

additional search fees were timely paid by the applicant. Consequently, this international
restricted to the invention first mentioned in the claims; it is covered by claims Nos.:

1, 5 , 22-27,

39-45 (completely)

Remark on Protest

search report is

ly)

'

The additional search fees were accompanied
' payment o f a protest fee.

'

The additional search fees were accompanied by the applicant's protest but the applicable
' fee was not paid within the time limit specified in the invitation.

I INo protest
Form PCT/ISA/21 0 (continuation

; 6-21(partial

search report covers

accompanied

of first sheet (2)) (April 2005)

by the applicant's protest and, where applicable, the

the payment o f additional search fees.

protest

International Application No.

FURTHER INFORMATION CONTINUED FROM

PCT/ISA/

PCTV I L2015/ 050442

210

Thi s Internati onal Searchi ng Authori t y found mul t i pl e (groups of)
i nventi ons i n thi s i nternati onal appl i cati on , a s fol l ows :

1. cl aims : 1, 5 , 22-27 , 39-45 (compl etely) ; 6-21 (parti al ly)
methods of determi ni ng tol erance t o an agent i n a heal thy
subject, based on a si gnature of a mi crobi ome; ki t thereof

2 . cl aims : 2-4(compl etely) ; 6-21 (parti al ly)
methods of determi ni ng an effect

of an agent on a mi crobi

ome

3 . cl aims : 28-38
methods of restori ng the tol erance of a subject t o an agent
compri si ng admi ni steri ng a probi oti c or an anti bi oti c
composi t i on

4 . cl aims : 46-50
methods of provi di ng an anti bi oti c or probi oti c treatment

International

FURTHER INFORMATION CONTINUED FROM

PCT/ISA/

Application

No.

PCTV I L2015/ 050442

210

Conti nuati on of Box I I .
Cl aims Nos . :

23 , 38

Cl aims 23 and 38 refer t o mi crobes di scl osed i n Tabl e 4 . However, i n the
present appl i cati on , Tabl e 4 (on page 125) di spl ays cl i ni cal parameters
such a s BMI and wai st-hi p rati o but no mi crobe or mi crobe ' s cl ass i s
di scl osed. Therefore,
cl aims 23 and 38 are total l y uncl ear and l ack
support (Arti cl e s 5 and 6 PCT) . Thi s l ack of cl ari t y was so severe that
no search coul d be performed on thei r subject-matter.

The appl i cant ' s attenti

on i s drawn t o the fact that cl aims rel ati ng t o
i nventi ons i n respect of whi ch no i nternati onal search report has been
establ i shed need not be the subject of an i nternati onal prel imi nary
exami nati on (Rul e 66. 1(e) PCT) . The appl i cant i s advi sed that the EPO
pol i cy when acti ng a s an Internati onal Prel imi nary Exami ni ng Authori t y i s
normal l y not t o carry out a prel imi nary exami nati on on matter whi ch has
not been searched. Thi s i s the case i rrespecti ve of whether or not the
cl aims are amended fol l owi ng recei pt of the search report or duri ng any
Chapter I I procedure. I f the appl i cati on proceeds i nto the regi onal phase
before the EPO, the appl i cant i s remi nded that a search may be carri ed
out duri ng exami nati on before the EPO (see EPO Gui del i nes C-IV, 7 .2) ,
shoul d the probl ems whi ch l ed t o the Arti cl e 17 (2) decl arati on be
overcome.

Patent document
cited in search report

US

2010172874

Publication
date

Al

08-07-2010

Patent family
member(s)

2102350
2010172874
2014093478
2008076696

Publication
date

A2

Al
Al
A2

23-09-2009
08-07-2010
03-04-2014
26-06-2008



Sign in to the Lens

Feedback