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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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application bearing no.2538/MUM/2007 containing

following claims,

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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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along with above explanation they have amended the claims

which reproduced as under,

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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.