1
BEFORE THE CONTROLLER OF PATENTS
PATENT OFFICE, MUMBAI,
PATENTS ACT 1970
(SECTION 15)
In the matter of Patent Act, 1970 and as
amended Patent (Amendment) Act 2005
In the mater of Patents Rule, 2003 and as
amended Patent (Amendment) Rule 2006
In the matter of Patent Application No.
1399/MUMNP/2010.
M/S.Cipla Limited - Applicant
Hearing Date: 20/02/2016
Present: - Dr.Indrani Bhattacharya, An authorized Patent Agent.
ORDER UNDER SECTION. 15
1. The instant Patent Application bearing No.
1399/MUMNP/2010 was filed on 30/06/2010, at Patent
Office, Mumbai, by M/s. CIPLA LIMITED, An Indian
Company, having its address at 289 Bellasis Road, Mumbai
Central, Mumbai, Maharashtra, India, filed an application for
grant of Patent for the titled invention “ANTI-RETROVIRAL
COMBINATION” claiming the priority of Indian patent
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2. The said Patent Application was published under section 11
(B) on 29/04/2011 in a Patent Office Journal and the Request for
Examination in Form -18 filed on 22/11/2011, the request no
assigned as 4197/RQ-MUM/2011.
3. After filing the Request for Examination the subject Patent
Application is examined in accordance with the provisions
of the Patents Act, 1970 (As amended) and under the Patent
Rules, 2003 ( as amended ) on examination the following
statement of objections have been generated the first
examination report was issued to their Authorized Patent
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Agent D.P.AHUJA & CO., 53, SYED AMIR ALI AVENUE, CALCUTTA 700
019, WEST BENGAL, INDIA on 27/10/2014, along with an indication
regarding last date for putting application in order for grant
and / or reply under section 21(1) of the Patents Act, 1970
( as amended) i.e on 27/10/2015
The Claims 1 to 22 do not constitute an invention u/s
2(1)(j) of the Patents Act, 1970, as they are not novel
and do not involve inventive step in view of the prior
published documents:
D1: WO 2006/055455; D2: WO2006005720A1; D3:
SEKAR V J ET AL: "Pharmacokinetic interaction
between darunavir boosted with ritonavir and
omeprazole or ranitidine in human
immunodeficiency virus-negative healthy
volunteers" ANTIMICROBIAL AGENTS AND
CHEMOTHERAPY, AMERICAN SOCIETY FOR
MICROBIOLOGY,-vol. 51, no. 3, 8 January 2007,
pages 958-961; D4: US 2005/084529; D5: WO
2006/091529.
D1 discloses a single solid dosage form comprising
darunavir (300 - 600mg) (p.5, lin. 11), tipranavir,
and optionally ritonavir (p.4, lin. 13-15).
D2 discloses an anti-HIV combination comprising (i)
tenofovir or its disoproxil fumarate derivative; (ii)
ritonavir; and (iii) TMC 114 (darunavir), useful for
the treatment or prevention of HIV infections. It
further relates to pharmaceutical formulations
containing such combinations. Each of the
ingredients of the combination according to the
invention can be co-formulated in one
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pharmaceutical form and do not have to be
administered in a separate pharmaceutical form. The
daily therapeutic antiretroviral amount of the
ingredients of the present combination of such co-
formulated single pharmaceutical form may then be
given in a single unit dosage form or even in
multiple unit dosage forms, such as two, three, four,
five or even more unit dosage forms. Such unit
dosage forms unit may contain for example about
300 mg of tenofovir disoproxil fumarate; for
example 100 to 400 mg, preferably 100 to 200 mg of
ritonavir; and for example 400 to 1200 mg, of TMC
114 (See abstract; page 7, lin. 1-10).
Therefore, claims 1, 8, 10, 12 and 22 are not novel.
D3 discloses the co-administration of ritonavir and
darunavir for the treatment of HIV. D3 does not
disclose a bi-layer tablet or the use of a polymer as
excipient, but only refers to the combined
application of the drugs. The problem to be solved
by the present invention may therefore be regarded
as providing a pharmaceutical composition which
contains ritonavir as well as darunavir. The solution
proposed in the present application cannot be
considered as involving an inventive stepbecause.
D4 and D5 already mention that pharmaceutical
compositions comprising one or more HIV protease
inhibitor can be prepared in form of bi-layer tablets
with a polymer as excipient. The tablets can be
prepared by using, for example melt- extrusion (D4:
[0073]; D5: p. 11, lin. 26 - p. 12, lin. 7).
In view of the above disclosures, it would have been
obvious for the skilled person to combine the
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teachings of D3 with that of D4 or D5. Therefore,
the claims 1-22 do not involve inventive step and do
not constitute an invention u/s 2(1)(j) of the Patents
Act, 1970.
2 Claims 10 and 22 are use claims, which are not
allowable u/s 2 (1) (j) of the Act, as what is claimed
therein does not constitute an invention as defined
under said Section of the Act.
3 Claim 12 are directed to methods of treatments,
which are statutorily barred from the patentability u/s
3 (i) of the Act and hence claims 12 is not a
patentable subject-matter as per the provision of said
Section of the Act.
4 Details regarding the search and/or examination
report including claims of the application allowed, as
referred to in Rule 12(3) of the Patent Rule, 2003, in
respect of same or substantially the same invention
filed in all the major Patent offices along with
appropriate translation where applicable, should be
submitted within a period of Six months from the
date of receipt of this communication as provided
under section 8(2) of the Indian Patents Act.
5 Details regarding application for Patents which
may be filed outside India from time to time for the
same or substantially the same invention should be
furnished within Six months from the date of filing
of the said application under clause(b) of sub
section(1) of secton 8 and rule 12(1) of Indian Patent
Act.
c) You are requested to comply with the objections
by filing your reply by way of explanation and/or
amendments within 12 months from the date of issue
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of FER failing which you application will be treated
as "Deemed to have been abandoned" under section
21(1) of the Act. The last Date is 27/10/2015.
d) You are advised to file your reply at the earliest so
that the office can further proceed with application
and complete the process within the prescribed
period.
4. An authorized Patent Agent D.P.Ahuja & Co, 53, Syed Amir
Ali Avenue, Calcutta – 700 019, on behalf of the Applicant
submitted their reply against to the first examination report
before expiry of the last date i.e. on 27/10/2015,
The reply to FER submitted reproduced below,
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5. On receipt of the reply further examination had been carried
out in accordance with section 13(3), thoroughly and found
that the reply as submitted could not complied the objection
raised in First Examination Report, and the Authorized Patent
Agent on behalf of the Applicant requested for an
opportunity of hearing being heard the case in case of any
adverse action Under section 14 of the Act,
6. Accordingly, a hearing being offered under section 14 of the
Patents Act, 1970 (as amended) to discuss an outstanding
objections raised at First Examination Report, having been
communicated following objections vide this Office letter No.
1791 Dated 02/02/2016, along with a date and time of
hearing was scheduled on 19/02/2016 at 12.00 am.
The submissions in your letter dated 20th Oct 2015 have
been considered carefully. The requirements of paragraphs 1-
2 of FER have not been met.
D6: US 2005/0048112.
D6 solid pharmaceutical dosage forms comprising
ritonavir (abstract and paras. [0037], [0084], [0085]) and,
optionally, further comprises a second species of HIV
protease inhibitor. D6 identifies 24 species of HIV
protease inhibitor other than ritonavir, including TMC-114
(darunavir), (see paras. [0013]-[0036], especially para.
[0027]). Therefore, D6 provides strong motivation to
formulate a solid pharmaceutical dosage form that
comprises both ritonavir and darunavir. D6 additionally
discloses that the solid pharmaceutical dosage form
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comprises "at least one pharmaceutically acceptable water-
soluble polymer" (abstract and para. [0008]).
D6 thereafter identifies "a copolymer of about 60% by
weight of the copolymer, N-vinyl pyrrolidone and about
40% by weight of the copolymer, vinyl acetate" as the
"particularly preferred polymer" (para. [0065]; see also
Tables 1 and 2 at paras. [0084]-[0085]).
D6 additionally discloses that " dosage forms according to
the invention may be provided as dosage forms consisting
of several layers, for example laminated or multilayer
tablets" (para. [0080]). D6 further discloses that
"multilayer forms have the advantage that two active
ingredients which are incompatible with one another can
be processed, or that the release characteristics of the
active ingredient(s) can be controlled" (para. [0080]). "For
example," D6 discloses, "it is possible to provide an initial
dose by including an active ingredient in one of the outer
layers, and a maintenance dose by including the active
ingredient in the inner layer(s )" (para. [0080]).
Referring to paragraph 1, the reply submissions are
unacceptable in view of D1-D5 and D6, composition
comprising darunavir and ritonavir and its use known from
D1-D6. Further claimed subject matter do not clearly
show advantage/surprising effect over prior art
composition.
Present claimed composition consider the new layered
form of a known combination of prior art, which are
statutorily barred from the patentability u/s 3 (d) of the Act
and hence claims 1-7 is not a patentable subject-matter as
per the provision of said Section of the Act. It is only the
therapeutic effect of the compounds in question, which is
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relevant for the assessment of inventive step and
patentability u/s 3(d), not the physical property.
6 The Applicants Authorized Patent Agent Ms.Indrani
Bhattacharya of the D.P.Ahuja & Co, has attended the
hearing , upon hearing the agent has submitted the written
reply and amended the claims. The reply as submitted
reproduce below,
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Findings:
7. At the outset, the alleged invention relates to a novel
antiretroviral combination in particular, to a pharmaceutically
stable composition and process for manufacturing the same
thereof, with a view to above the inventors have developed a
phamramceutical composition having novel antiretroviral
combination which may be administered simultaneously,
separately or sequentially, which has the superior efficacy ,
and the combination has highly potent against wild type and
multidrug –resistant HIV strain.
8. Accordingly, the final primary claim amended after hearing
which reads as follow,
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9. The outstanding objection pertain to inventive step and
section 3(d) still remain due to following reason that the ,
Claims 1 to 8 do not constitute an invention u/s 2(1)(j) of the
Patents Act, 1970, as they do not involve inventive step in
view of the prior published documents: the most closest prior
art D3: SEKAR V J ET AL: "Pharmacokinetic interaction
between darunavir boosted with ritonavir and omeprazole or
ranitidine in human immunodeficiency virus-negarive
healthy volunteers" ANTIMICROBIAL AGENTS AND
CHEMOTHERAPY, AMERICAN SOCIETY FOR
MICROBIOLOGY,-vol. 51, no. 3, 8 January 2007, pages
958-961; D3 discloses the co-administration of ritonavir and
darunavir for the treatment of HIV cited and discussed
during the course of hearing along with co – cited documents
D1, D4 – D6.
The D1: WO 2006/055455;
D1 discloses a single solid dosage form comprising darunavir
(300 - 600mg) (p.5, lin. 11), tipranavir, and optionally
ritonavir (p.4, lin. 13-15).
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D2: WO2006005720A1 discloses an anti-HIV combination
comprising (i) tenofovir or its disoproxil fumarate derivative;
(ii) ritonavir; and (iii) TMC 114 (darunavir), useful for the
treatment or prevention of HIV infections. It further relates to
pharmaceutical formulations containing such combinations.
Each of the ingredients of the combination according to the
invention can be co-formulated in one pharmaceutical form
and do not have to be administered in a separate
pharmaceutical form. The daily therapeutic antiretroviral
amount of the ingredients of the present combination of such
co-formulated single pharmaceutical form may then be given
in a single unit dosage form or even in multiple unit dosage
forms, such as two, three, four, five or even more unit dosage
forms. Such unit dosage forms unit may contain for example
about 300 mg of tenofovir disoproxil fumarate; for example
100 to 400 mg, preferably 100 to 200 mg of ritonavir; and for
example 400 to 1200 mg, of TMC 114 (See abstract; page 7,
lin. 1-10).
D3 discloses the co-administration of ritonavir and darunavir
for the treatment of HIV. D3 does not disclose a bi-layer
tablet or the use of a polymer as excipient, but only refers to
the combined application of the drugs. The problem to be
solved by the present invention may therefore be regarded as
providing a pharmaceutical composition which contains
ritonavir as well as darunavir. The solution proposed in the
present application cannot be considered as involving an
inventive step because. D4 and D5 already mention that
pharmaceutical compositions comprising one or more HIV
protease inhibitor can be prepared in form of bi-layer tablets
with a polymer as excipient. The tablets can be prepared by
using, for example melt- extrusion (D4: D4: US 2005/084529;
[0073]; D5: D5: WO 2006/091529 p. 11, lin. 26 - p. 12, lin.
7).
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10. D6: US 2005/0048112.
D6 solid pharmaceutical dosage forms comprising ritonavir
(abstract and paras. [0037], [0084], [0085]) and, optionally,
further comprises a second species of HIV protease inhibitor.
D6 identifies 24 species of HIV protease inhibitor other than
ritonavir, including TMC-114 (darunavir), (see paras. [0013]-
[0036], especially para. [0027]). Therefore, D6 provides
strong motivation to formulate a solid pharmaceutical dosage
form that comprises both ritonavir and darunavir. D6
additionally discloses that the solid pharmaceutical dosage
form comprises "at least one pharmaceutically acceptable
water-soluble polymer" (abstract and para. [0008]).
D6 thereafter identifies "a copolymer of about 60% by
weight of the copolymer, N-vinyl pyrrolidone and about 40%
by weight of the copolymer, vinyl acetate" as the
"particularly preferred polymer" (para. [0065]; see also
Tables 1 and 2 at paras. [0084]-[0085]).
D6 additionally discloses that " dosage forms according to
the invention may be provided as dosage forms consisting of
several layers, for example laminated or multilayer tablets"
(para. [0080]). D6 further discloses that "multilayer forms
have the advantage that two active ingredients which are
incompatible with one another can be processed, or that the
release characteristics of the active ingredient(s) can be
controlled" (para. [0080]). "For example," D6 discloses, "it is
possible to provide an initial dose by including an active
ingredient in one of the outer layers, and a maintenance dose
by including the active ingredient in the inner layer(s )" (para.
[0080]).
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the reply submissions are unacceptable in view of D1-D5 and
D6, composition comprising darunavir and ritonavir and its
use known from D1-D6. Further claimed subject matter do
not clearly show advantage/surprising effect over prior art
composition.
Present claimed composition consider the new layered form
of a known combination of prior art, which are statutorily
barred from the patentability u/s 3 (d) of the Act and hence
claims 1-8 subject-matter as per the provision of said Section
of the Act.
In view of the above disclosures, it would have been obvious
for the skilled person to combine the teachings of D3 with
that of D4 or D5-D6. Therefore, the claims 1-8 do not
involve inventive step and do not constitute an invention u/s
2(1)(j) of the Patents Act, 1970.
11. In view of above finding and upon consideration of all
the documents available on record and in view of above
outstanding objections, under the circumstances of the case, I
refuse to grant the Patent on this Patent application No.
1399/MUMNP/2010
Dated this 01st Day of April, 2016.
(N.Ramchander)
Dy. Controller of Patents & Designs
Copy : - Ms. Indrani Bhattacharya of D.P.Ahuja & Co, 53, Syed
Amir Ali Avenue, Calcutta – 700 019.