THE PATENTS ACT, 1970 (As amended by Patent Act 2005) & The Patent Rules 2003 (As amended by Patent Rules,2006)

In

the

matter

2632/DELNP/2005

of

Patent

made

by

Application

no.

BOEHRINGER

INGELHEIM PHARMA GMBH &CO. KG., A German company, of Binger Strasse 173, D-55216 Ingelheim, Germany

And In the matter of representation by way of an opposition thereto by CI PLA Ltd. An Indian company Of LBS Marg, Vikhroli, Mumbai.

And IN THE MATTER In of opposition U/S 25(1) of Indian Patent Act,1970 and

Rule 55 of the

Patent Rules. Hearing Held on 27th March, 2008 Present:: Mr. SHUKDEV KHURAIJAM………………………….Agents for the Applicant Mr. R. K. Dewan……………………………………… Agents for Opponent

DECISION An application for Patent No. 2632/DELNP/2005 was filed by M/S Remfry & Sagar at Delhi on 15.06.2005 for grant of Patent on behalf of the applicants M/S Boehringer Ingelheim gmbh & Co, Germany for an Invention Titled “Powder medicament for inhlation comprising a tiotropium salt and salmeteral xinafoate” 1

The application as filed had 16 claims the first claim pertained to "Inhalable powder containing tiotropium 1' and salmeterol xinafoate _2 which is characterized

by

a

melting

point

of

about

124°C,

mixed

with

a

physiologically acceptable excipients." And claims 15 & 16 pertained to Inhalation Kit, The request for examination was filed on 15.06.2005 and the first Examination report sent by the Examiner on 16.10.2007 with objections that the invention is not patentable due to lacking of Novelty and inventive step u/s 2(1) j a and claims 15 & 16 falls u/s 3(f) of the Patent Act 1970, The response for FER has been filed by the Agent for applicant on 29.02.2008 with revised claims and the No. of claims were radiuses to 12, Claims 1 to 9 & 12 pertained to “A capsule containing an inhallable powder and claims 10 to 11 pertained to kit . A pre grant opposition u/s 25(1) by way of representation was filed by m/s CIPLA,Ltd hearinafter referred as opponent, an Indian compny of LBS marg, Vujgroli(w) Mumbai, Maharastra India through there representative m/s R.K.Dwan & Compny, Trade marks & Patents Attorneys podar chambers, S.A. Brelvi Road, Fort Mumbai on 29.08.2007 and a copy of representation by way of opposition filed by the opponent has been sent to Agents for applicants on 16.10.2007, A reply statement has been filed by the applicants agent on 16.01.2008, The case was heard by the controller on 27.03.2008. The opponents raised various issues in their representation and during the course of their arguments that were heard at length on 27.03.2008, Now I have discuss each remaining Issue in details herein below.

Novelty Section 25(1)(b) that the invention as far as claimed in the claim of the complete specification has been published before the priority date of the claim: (ii) In India or elsewhere in any other document. Section 25(1)(c) that the invention so far as claimed in any claim of the complete specification is claimed in a claim of a complete specification published on or after priority date of the applicant’s claim and filed in pursuance of an application for a patent in India, being a claim of which the priority date is earlier than that of the applicant’s claim;

2

Opponent submitted that a synergistic combination of salmeterol xinafoate and titropium is disclosed in WO00/69468, published on 23rd Nov.2000,which is well before the priority date of the 2632/DELNP/2005 application (Claimed Priority date of the 2632/DELNP/2005 application 20th Dec,2002). The PCT equivalent patent application for the 2632/DELNP/2005 application disclose and claim the same manner in material particular, the finding of the International Search Report (ISR) published along with the PCT equivalent hold true for the 2632/DELNP/2005 application without any limitation. Provided herein below is a list of “X” type of documents as cited in the International Search Report of the aforementioned PCT equivalent. •

WO 02/060532 A ( BOEHRINGER INGELHEIM PHARMA ; BOZUNG KARL-HEINZ (DE); WALLAND ALEXANDE) 8 August 2002 (2002-08-08).

•

WO 02/38154 A ( BOEHRINGER INFELHEIM PHARMA; NAGEL JUERGEN (DE); SCHMELZER CHRISTEL() 16 May 2002 (2002-05-16)

•

WO 00/69468 A ( BOEHRINGER INGELHEIM PHARMA; BOZUNG KARL HEINZ ( DE); WALLAND ALEXANDE) 23 Nov 2000 (2000-11-23)

•

WO 02/30390 A ( BOWHRINGER INGEHIEM PHARMA ; BOECK GEORG (DE); WALZ MICHAEL (DE) 18 APRIL 2002 (2002-0418)

An “ X” type document as defined in international Search Report is a document of particular relevance on the basis of which the invention can’t be considered to be novel when such document is taken alone.

Opponent further submitted that the body of the originally filed specification. Pages 2-5 deal with prior art and problems in the prior art. The admissions made in the prior art by the Applicant are as follows: 3

•

Tiotropium bromide is known from European Patent Application EP418716. (Page 1, line 6)

•

The betamimetic salmeterol is also known from the prior art. (Page 1, line 13)

•

Pharmaceutical combinations of long acting betamimetics with long acting anticholinergics which are characterized by the synergistic effect (Pagel, last paragraph)

•

Specific pharmaceutical combination of titotropium bromide and salmeterol xinafoate.(page2,line1)

Moreover, by Applicant own admission, a pharmaceutical combination in the forms of inhalable powder composition comprising salnieterol xinafoate and tiotropium bromide showing synergistic effect is known through PCT Application WOOO/69468[corresponding Indian Patent 211375granted on Equivalent Indian Application 382/MUMNP/2005 was submitted to the Controller during hearing). In accordance with 3(d) of the act the polymorph of salmeterol having melting point of about 124 °C will have to be treated as same substance, since no data as regards to enhanced efficacy of the new form or of the combination as a whole over the known combination is provided in the specification. It is therefore sincerely submitted that u/s 25(1) b read with 3 (d) all the claims of the 2632/DELNP/2005 application should be rejected for being non-novel over the disclosures made in the above mentioned patent document. Agent for Applicant submitted that International Preliminary Examination Report, has considered the invention disclosed in this Patent application no. 2632/DELNP/2005, novel after taking into due consideration the documents cited in the International Search Report. It is once again reiterated that the Opponent chose to ignore the International Preliminary Examination Report and myopically highlighted the International Search Report only in a juvenile attempt to mislead the Controller.

With respect to the document WO 00/69468, it has been incorporated in the specification of the Applicant’s patent application. This document report about the finding that the co-administration of a long-acting anti-cholinergic drug, 4

preferably a Tiotropium salt (1), and a long-acting beta-2-agonist(LABA), preferably Formoterol or Salmeterol in a suitable salt form (2), exhibit synergistic (in the meaning of over-additive) effects with respect to reduction of an induced bronchospasm

in

animals.

The

possibility

to

combine

a

long-acting

anticholinergic drug (1) and a LABA (2) can be deduced from the teaching of WO 00/69468 A1. The given formulation examples do not contain any specific information on optimized formulations in the sense as defined in the Applicant’s impugned application. The said prior art document does not anticipate the invention as disclosed in the original claims (as evident from the IPER) as well as the amended set of claims filed thereafter with the response to the first examination report which is directed to a capsule containing as inhalable powder comprising a tiotropium salt and Salmeterol xinafoate with the parameters as disclosed in the main claim. It is a well established patent principle that single documents should anticipate the invention in question in entirety if the document is to be considered to destroy the novelty of the invention in question. Since, the Opponent failed to present or identify any document in this context, the ground of lack of novelty under Section 25(1)(b) taken by the Opponent is not maintainable and hence should be rejected.

Applicant further submitted that the opponent has chosen to deliberately mislead and confuse the learned Controller in a juvenile attempt at garnering a prima facie opinion in his favor. It is not disputed that the prior art documents WO 02/060532, WO 02/38154A, WO 00/69468A and WO 02/30390 have been cited in the "X" category in the International Search Report (ISR). The opponent's elucidation on the significance of an "X" type document with respect to the novelty of an invention is also not disputed. However, it is to be appreciated that the International Search Report is the basis on which the International Preliminary Examination Report (IPER) is rendered. Accordingly, the learned Controller's attention is respectfully invited to the IPER, which has been carried out by the same searching authority on the basis of all pertinent documents including those mentioned by the opponent. The opponent has enclosed the same as "Exhibit II" in its representation. The

5

relevant portion of the IPER with respect to novelty is reproduced below for the learned Controller's reference: "The subject matter of the present application is novel since none of the cited

documents

describes

an

inhalation

powder

containing

tiotropium(Tio) and Salmeterol xinafoate(SalX)characterized by a melting point approximately 124°C, mixed with a physiologically unproblematic auxiliary substance." The above paragraph is clear affirmation of the novelty of the subject matter of the application as filed by the applicant.

I agree that it is a well-established patent principle that single documents should anticipate the invention in question in entirety if the document is to be considered to destroy the novelty of the invention in question. The same has also been admitted by the opponent when “X” category document is defined in their submissions which is as follows: An “X” type document as defined in international Search Report is a document of particular relevance on the basis of which the invention can’t be considered to be novel when such document is taken alone. I also agree that the document WO 00/69468 do not disclose the formulation, which contains specific information on optimized formulation in the sense as defined in the Applicant’s impugned application. It is further observed that none of the document in single discloses, teaches or suggests entirely that “The subject matter of the present application is novel since none of the cited documents describes an inhalation powder containing tiotropium(Tio) and Salmeterol xinafoate(SalX)characterized by a melting point approximately 124°C, mixed with a physiologically unproblematic auxiliary substance."

Therefore, I conclude that invention disclosed in this impugned patent application shall be considered as novel. Consequently, these grounds cannot be maintained and is liable to be rejected.

6

Inventive step

Section 25(1)(e): that the invention as far as claimed in the claims of the complete specification does not involve any inventive step, having regard to matter

published

in

Indian

patent

application,

other

documents

and

specifications of Indian patent and foreign patent, and having regard to what is used in India before the priority date of the claims. The Opponent submitted that the subject matter of the invention as claimed in claims 1 to 12 lacks an inventive step and is obvious to a person skilled in the art in the light of the prior art known to a person skilled in the art. Provided herein below is a summary of combined prior art references which teach, suggest and provide substantial background to motivate a person skilled in the art to conceive the invention as claimed in the 2632/DELNP/2005 application.

a. PCT application WOOO/28979, published on 25.05.2000 and its equivalent US Patent 6645466 Keller discloses “ a dry powder formulation for inhalation” preferably comprising magnesium stearate to improve moisture resistance, a betamimetic, and/or an anticholinergic, and/or a corticosteroid in the form of a pharmaceutically acceptable salt or ester , wherein suitable betamimetics

include

salmeterol

xinafoate,

and

suitable anticholinergics include tiotropium bromide. The typical active concentration in the formulation can be approximately 0.1-10% by weight,in particular 0.1-5% by weight based on the total formulation . Inhalable dry powders are known to be stored in pre-dosed units, such as capsules and blister packs

and that the use of magnesium-stearate containing

formulations is suitable for improving the resistance to moisture of predosed units, for example, in the form of capsules . The active agents to be inhalable these must be obtained having a particle size of approximately 1 - 1 0 microns, preferably 1-6 microns, which can be obtained by conventionally known techniques, such as controlled precipitation, micronization, or by spray drying. Suitable carriers include mono- or disaccharides, such as glucose (i.e. a monosaccharide), lactose (i.e. a

7

disaccharide), lactose monohydrate, sugar alcohols, etc., wherein lactose monohydrate is particularly preferred.

b.

US Patent 5795594 (PCT WO9501324), york [published on 18th August, 1998] teaches salmeterol xinafoate polymorph with a melting point of about 123.5 °C [Refer Fig 4, peak heat flow from 119.94 to124.3 °C] with and having bulk density 0.137g.cm~3, which is closer to0.134 g.cm3 .

c.

WO/0069468 and its equivalent granted Indian patent 211375 an inhalable pharmaceutical composition comprising

teaches

salmeterol

salt

application

CA

and tiotropium salt.

d.

WO02/38154 2429012

and

discloses

its a

Equivalent capsule

Canadian

containing

an

inhalable

powder

formulation comprising salmeterol sulfate and tiotropium bromide with a total inhalable powder fill of 5mg. This Application also indicates the use of

salmeterol xinafoate .

e. US application US 20020179087 provided hereto and attached herewith as teaches a capsule containing inhalable powderd formulation comprising

salmeterol

xinafoate

and

oxitropium

bromide

and lactose (disaccharide carrier) with a powder fill of 12.5mg wherein the proportion of salmeterol xinafoate in the inhalable powder is 0.4% by mass of the total mass of the inhalable powder inside a capsule.

f.

US application 2002/0189610 teaches a capsule containing inhalable powder formulation comprising salmeterol xinafoate and ipratropium bromide wherein the proportion of salmeterol xinafoate in the inhalable powder is 0.4% by mass of the total mass of the inhalable powder inside a capsule.

8

It would have been but obvious for a normal person skilled in the art to employ one of the known polymorphs having known physicochemical properties in an inhalable powder formulation and encapsulating such formulation. An ordinary skilled artisan would have had a reasonable expectation of success upon combination of tiotropium bromide and salmeterol xinafoate to obtain a inhalable dry powder, because both compounds are known for use in inhalable formulations and their combination is suggested by the prior art.

Regarding the proportion of salmeterol xinafoate with respect to the total mass of the inhalable powder in a capsule, encapsulated formulation with salmeterol xinafoate in an amount of 0.4 % by mass of the total mass of the inhalable powder [which is within the range of 0.363% to 0.508% ] were disclosed in two US applications US 20020179087 and US application 2002/0189610 in the name of the applicant before the claimed priority date of the 2632/DELNP/2005 application. Again with respect to claim 10 and 11 of the amended set of claims the accompanying diagram of the inhalation kit as published in the 2632/DELNP/2005 application and the accompanying diagram of the inhalation kit as published in US application 2002/0189610 in the name of the applicant are strikingly similar. Against the backdrop of the knowledge of inhalation kit as disclosed in US application 2002/0189610 the inhalation kit as claimed in claims 10 and 11 of the 2632/DELNP/2005 application is obvious to a person skilled in the art.

AIR 1981 SUPREME COURT 1444, Patents Act (39 of 1970), S.2 (1) (j), and S.64.

It is important that in order to be patentable an improvement on something known before or a combination of different matters already known, should be something more than a mere workshop improvement; and must independently satisfy the test of invention or an 'inventive step'. To be patentable, the improvement or the

combination must produce a new process or improved

results. Mere collection of more than one integers or things not involving the exercise of any inventive faculty, does not qualify for the grant of a patent, (para 21)

9

In Ram Narain Kher v. M/s., Ambassador Industries New Delhi & others., AIR 1976 DELHI 87, PRITHVI RAJ. J, It was held that "It would therefore be seen that having regard to the previous date of knowledge at the time the patent is granted to a party it is essential that the party claiming patent should specify what particular features of his device distinguish it from those which had gone before and show the nature of the improvement which is said to constitute the invention. A person claiming a patent has not only to allege the improvement in art in the form but also that the improvement effected a new and very useful addition to the existing state of knowledge. The novelty or the invention has to be succinctly stated in the claim. It is no doubt true that the claim made is addressed to the skilled persons in the art or trade and not a common man yet there can be no escape from the fact that the novelty of the claim or the advantage derived by the invention has to be succinctly stated in the claim and must not to be left to an inference raised on a general review of the specification"

Opponent

further

submitted

that

the

even

the

International

Preliminary

Examination Report issued in respect of the corresponding PCT Application has declared the subject matter of the 2632/DELNP/2005 application to be obvious.

Furthermore, all the claims of the corresponding US application 20040152720 have been rejected before the abandonment of the application on the grounds of being obvious. Similarly, the claims made in another corresponding application US 2007 0128125 have also been rejected in a non-final rejection based on similar ground.

Also in accordance with the English translation of International Preliminary Report (published on 27th July 2005) IPER subject matter of the alleged invention as disclosed in the PCT equivalent is obvious and it does not involve an inventive step.

Provided herein below are the findings from IPER that substantiates the lack of inventive step in the alleged invention as disclosed in the 2632/DELNP/2005 application.

10

•

“D6 (WO 02/30390) the document which is considered the closet prior art, disclose a method for producing inhalation inhalation powders containing an active substance combination which can be an anticholinergic with a betamimetic ( see page 8, lines 23-29). Tiotropium bromide is the preferred anticholinergic (see page7, line11) and Salmetrol xinafoate is the preferred beat mimetic ( see page 6, line 30). The method enable the production of inhalation powders characterized by a high degree of homogeneity in the sense of the uniformity of content and accuracy of individual dosing ( see page 1, lines 33-35 and page 9,lines 1-10).

•

The only difference between the aforementioned closest prior art document and the 2632/DELNP/2005 application is characterized by a melting point of 124.C, whereas there is no indication as to the melting point of the salmeterol xinafote used in the prior art document D6 (WO 02/30390).

ii.

The alleged invention as disclosed in the 2632/DELNP/2005 application is directed to prepare an inhalable powder containing a tiotropium salt and salmeterol xinafoate, which is characterized by a high degree of homogeneity and uniformity of dispersion. (Page5, lines 1-3 of 2632 application is to provide an inhalable powder, which allows the inhalable provide an inhalable powder, which allows the inhalable proportion of active substance to be administered with lowest possible variability. (page 5, lines 3-5 of the 2632/DELNP/2005 application)

The problem addressed in the 2632/DELNP/2005 application is therefore how to obtain inhalable powders having the aforementioned advantages.

The

solution

proposed

to

the

aforementioned

problem

in

the

2632/DELNP/2005 application is the use of a salmeterol xinafote characterized by a melting point of approximately 124*C.

11

Provided herein below are the findings from the IPER which cite three documents, the combined teaching of which render the alleged invention in the 2632/DELNP/2005 application obvious.

a. D7 (see abstract) or D8 (page 9, lines 1-5, table on page 10, page 11,claim 23) or D9 (column 1, lines 5-10, examples 1-4,9,11,12 claims 1,9, 11,13-15,figures 4,5,22-23,30,34-36,44-48) teach that salmeterol xinafoate (Sal X) characterized by a melting point of approximately 124*C or an x-ray diagram as in the 2632 application enables the production

of

inhalation

powder

having

less

agglomeration,

electrostatic charge and adhesion. b. To a person skilled in the art, it is obvious to combine the teaching of D7, D8 or D9 with the proposed active substance ( salmeterol xinafote and a titropium salt) combination and method of production of D6 ( or D3- D5) so as to arrive at the alleged invention as provided in the 2632 application. iii.

Reproduced herein below is the opinion provided in IPER as far as the in Inventive step involved in the alleged invention as disclosed in 2632 application is concerned:

“It is not possible to acknowledge

“an inventive step , since the

invention appears to consist merely in the succession of a combination of known features which each function in a normal manner, which does not give rise to an inventive functional interaction” It is therefore respectfully submitted that the alleged invention as disclosed in the 2632/DELNP/2005 is obvious to a person skilled in art. Accordingly, claims of the 2632/DELNP/2005 application lack an inventive step.

Applicant submitted that the arguments on inventive step were lifted from the observations in the International Preliminary Examination Report. The Opponent further lifted arguments from the official letters of the corresponding applications of the US applications mainly based on the prior art documents cited therein.

12

The Opponent also alluded to two Supreme Court decisions which highlighted the fact to be patentable that an improvement on something known before or a combination of different matters already known should be something more than a mere workshop improvement and must independently satisfy the test of inventive step. The case laws presented by the Opponent’s Attorney merely provides an insight to the definition of inventive step as laid down under Section 2(1)(j) of the Indian Patents Act.

The Opponent went further and made a wrong and misleading submission that the corresponding applications (US 10/736,264 and US 11/537,674 have been finally abandoned/rejected in the face of some of these citations. The Applicant clarified that US 10/736,264 was abandoned not for the reasons of the prior art documents cited against but on the filing of a continuation application, which is US 11/537,674. The Opponent further contended that US 11/537,674 has been finally rejected in the official letter dated August 13, 2007. The Applicant apprised that it was just another gross and wrong submission as the said official letter is not a final rejection letter and moreover, a response to the same has been filed on February 11, 2008 with claims which are similar as those pending in the subject Indian application conclusively rebutting the Examiner’s objections.

The Applicant also presented the “Technical Affidavit” from Prof. Steckel in support of the inventive step of the invention disclosed in the subject application. The Applicant further submitted that considering the prior art cited, the problem to be solved is to provide an inhalable powder with improved stability and more even disability. It is submitted that the said qualities are achieved by the claimed invention as follows: •

A first requirement is that there is a range for both tiotropium and Salmeterol xinafoate in terms of the amount per dosage. This amount should be sufficient to achieve the desired therapeutic effect.

•

A second requirement is to dilute the active compounds in order to guarantee even disability, because the amount required for achieving the therapeutic effect are small and thus a broad variability of the

13

actual delivered doses would result from their administration in pure form. This is why carriers are used. •

In summary, sufficient amounts of the actives at the right degree of dilution by carriers are to be administered. Thus, the problem to be solved is to find the optimum capsule fill weight satisfying the aforementioned

requirements

while

providing

good

product

functionality. Based on this framework of requirements, capsules containing from 8 to 12 mg inhalation power have proven beneficial. •

It has been found now, that in case of capsules containing a fill weight of from 8 to 12 mg inhalable powder, the stability of the active compounds depends from their concentration, i.e. the ratio between their amount and the amount of the carrier. Salmeterol xinafoate stability decreases with increasing fill weight, i.e. with decreasing Salmeterol xinafoate concentration. It has been found that 400C/75% r.h. the Salmeterol xinafoate ratio decreases by 4.8% over a period of 3 months at a capsule fill weight of 5.5 mg; by 5.8% at a capsule fill weight of 11 mg and by 7.9% at a capsule fill weight of 16.5 mg, all for Salmeterol xinafoate weights of 50μg.

Further, it has been found that the variation of the delivered dose of 50μg Salmeterol xinafoate at 400C/75% r.h. decreases more when increasing the capsule fill weight from 5.5 mg to 11 mg than by increasing the capsule fill weight from 11 mg to 16.5 mg. Specifically, delivered dose variation is 6.9% at 5.5 mg fill weight, 4.1% at 11 mg fill weight and 2.7% at 16.5 mg.

Moreover, it has been found that the fine particle dose (<5μm) of 50 μg salmeterol amounts to 20.0 μg at a capsule fill weight of 5.5. mg to 18.0 μg at a capsule fill weight of 11 mg and to 16.4 μg at a capsule fill weight of 16.5 mg, which reflects a significant decrease.

14

The capsule fill weights from 8 mg to 12 mg are optimal because the fine particle dose is high, the variation of the delivered dose is already lower and the stability of Salmeterol in the composition is still high.

As regards the citations referred in the International Preliminary Examination Report and those dwelled upon by the Opponent, it is submitted that:

Schmelzer and Nagel (WO 02138154 A1) describes a novel medicament composition containing a Tiotropium salt (1) and a Salmeterol salf (2) either combined dosage form or divided into two separate dosage forms. The rationale for such a combined use of a (long-acting) anti-cholinergic drug (1) and a long-acting beta) is based on the finding that the co-administration of these two drugs leads to an unexpected synergistic treatment effect. Different dosage forms and formulations are described in this patent application, among those aqueous-based solutions for the use with a soft-mist inhaler and propellant-based formulations to be used with a metered dose inhaler.What is claimed is inhalation containing the two active moieties with or without a physiologically acceptable carrier. Additionally, a preferential particle size is given for the carrier substance. Furthermore, it is claimed that the powder blend is filled into capsules and could be dry powder inhalation device. The examples given in the description of the invention contain 10.8 μg of (1) and 27.9 μg of (2) in a powder blend of 5 mg total mass. Other formulation examples contain a higher amount of actives in the total mg powder formulation importantly, formulations are excluded containing Tiotropium bromide and Salmeterol xinafoate; all examples given make reference to salt of Salmeterol.

In summary, it is the teaching of WO 02/38154 A1 that co administration of the longacting anti-cholinergic drug Tiotropium bromide and any salt of the long-acting beta2-agonist Salmeterol is beneficial for the therapy of respiratory disorders. General, but non-optimized formulations of the aqueous-based systems, metered dose inhalers and dry powder formulations are described. Non-optimized in this context shall mean that applications are only given for clarity reasons. The cited formulations are not optimized to any of the specific requirements of inhalation drug products such as chemical and physical stability and dose delivery characteristics.

15

In WO 00/69468 A1, Pairet et al report about the finding that the co-administration of a long-acting anti-cholinergic drug, preferably a Tiotropium salt (1), and a longacting beta-2-agonist, preferably Formoterol or Salmeterol in a suitable salt form (2), exhibit synergistic (in the meaning of over-additive) effects with respect to reduction of an induced bronchospasm in animals. In addition, the simultaneous administration of such two compounds significantly reduces the typical side effects of (2), such as the typically found increase in heart beat rate of the studied animals. Again formulation examples are given for metered dose inhalers, aqueous-based systems and carrier-based dry powder formulations. One example for a dry powder formulation is given in the descriptive part of the invention, which contains 6 μg of Tiotropium bromide and 6 μg of Formoterol fumarate in their respective stable hydrate forms in a powder blend of 25 mg Lactose monohydrate. This powder blend is then filled into capsules which chemical composition is not further specified. Such composition is then also included into the dependent claim 13 which discloses a blend of (1) and (2) and eventually a carrier. Again, no specific details are given on either the ratio of (1) and (2) and no information is provided on the total quantity of the powder to be filed into capsules.

In summary, the possibility to combine a long-acting anticholinergic drug (1) and a LABA (2) can be deduced from the teaching of WO 00/69468 A1. The given formulation examples do not contain any specific information on optimized formulations in the sense as defined above.

In WO 02/060532 A1, Bozung et al. report about a comparable finding as described in the previous patent applications. The main finding as described in this document is that the co-administration of Ipratropium salts (1) and long-acting beta-2-agonists (2) is able to reduce the systemic side effects caused by the LABA substance. In a preferred embodiment of the described invention, the combination products contain the anticholinergic drug (1) Ipratropium bromide (as referred to in examples A. 1A.3, B.1 – B3 and C.1 – C.4) and the LABA’s Formoterol fumarate dihydrate or Salmeterol in form of its xinafoate or hemisulfate salt (2). Also in this patent application, exemplifications are given for metered dose inhalers, aqueous-based systems and dry powder inhaler formulations. Typical examples for such dry powder inhaler formulations are given in claims 12-16 and claim 36, disclosing 16

powder formulations containing (1) and (2) plus a physiologically acceptable carrier substance or a mixture of such carrier substances. Also, the particle size distribution of the carrier substances is specified. The powder formulations are filled into capsules and are administered to the patient’s lung with a device known as Handihaler. Carrier-free compositions may be used as well. The exemplifications given in the description of the application contain 100 or 200 μg of Ipratropium bromide and either 12 μg Formoterol fumarate dihydrate or 50 μg Salmeterol xinafoate The carrier used in exemplify the powder compositions is Lactose monohydrate in a quantity of up to 12.5 mg and 25 mg of total powder mass per dose respectively. No additional teaching on the composition of the powder blends can be derived from the disclosed examples.

In summary, the teaching that can be derived from this patent specification is that the co-administration of Ipratropium salts and a LABA is able to reduce the typical side effects seen after single administration of LABA’s. The exemplifications of potential formulations are non-specific and common knowledge to a formulation scientist.

While the subject of three discussed documents (WO 02/38154 A1, WO 00/69468 A1, WO 02/060532 A1) is the combination of anti-cholinergic drug substances with longbeta-2-agonists, supplemented with formulation exemplifications for fixed combination products of these drugs, the teaching of WO 02/30390 A2 by Boeck and Walz is how to obtain a homogeneous powder blend consisting of a carrier material and an active drug substance. The carrier material preferably has an active drug substance. The carrier material preferably has an average particle size from 15 to 80 μm and may contain a suitable amount of finely divided carrier particles having an average particle size of 1 to 9 μm, whereas the active drug substance is present in micronized form, i.e., has got an average particle size from 0.5 to 10 μm. Described and claimed is a process to obtain a homogeneous powder blend of said substances, specified in that the powders are charged in layers into the mixing vessel and subsequently blended. Different formulation examples are given to exemplify the invention describing the charging procedure of the powders and the blending process. The examples given represent the state of the art knowledge on how to compose a formulation for dry powder inhalation. Those exemplified 17

compositions contain Lactose monohydrate as a carrier and Tiotropium bromide monohydrate at a level) of 22.5 pg per dose in a total powder mass of 5.5 mg, such powder being filled into either hard gelatine or polyethylene capsules Such powder blends may also contain more than one active drug substance.

In summary, the teaching of WO 02/30390 A2 is a specific blending process to obtain homogeneous powder blends of one or more micronized active substances and a carrier material, such as Lactose monohydrate.

US 6645466 relates to improving moisture resistance and stability of powder formulations by including magnesium stearate in those formulations. As asserted by the Opponent, the said document discloses combinations of betaminetics and anticholinergics but lacks the express teaching of Salmeterol xinafoate being characterized by a melting point of about 1240C. US 5795594 according to the Opponent, cures this defect. However, both documents do not disclose all the features of claim 1, namely weight percent of salmeterol xinafoate in the inhalable powder and the total amount of inhalable powder in the capsule, the importance of which has been discussed and is one again reiterated.

An objective of the present invention is to provide an inhalable powder with improved stability and with little to no variability in dosing. For example, tiotropium and salmeterol xinafoate should be present inan amount per dose that achieves a desired therapeutic effect. However, it is necessary to dilute the active compounds with an excipients/carrier(s) in order to guarantee an even distribution during administration. This is true because the amount of active required for achieving a therapeutic effect if small and there would be large variability in the actual delivered dose resulting from administration in pure form. The objective is thus to prepare an inhalable powder where there is a sufficient amount of active for a therapeutic effect, while achieving the correct dilution of the actives with carriers/excipients. The presently claimed invention describes the optimal capsule fill weight satisfying the aforementioned requirements while providing good product functionality. It has been discovered that in case of capsules containing a fill weight of from 8 to 12 mg inhalable powder, the stability of the active compounds depends from its concentration, i.e., the ratio between the active amount and carrier amount. Thus, 18

capsule fill weights from 8 mg to 12 mg are optimal because the fine particle dose is high, the variation of the delivered dose is already lower and the stability of Salmeterol in the composition is still high. Therefore, the teachings of these two documents even when combined do not obviate the inventive step of presently claimed invention.

The combination of active drug substances within one inhalation powder formulation can be regarded as prior art. Specifically, the combination of anti-cholinergic drug substances and long-acting beta-2-agonists are well described in the mentioned documents. Also, the teaching of the manufacture of homogeneous powder blends of such substances with an inert carrier can be derived from the literature.

During the formulation of the inhalation drug product in question containing a therapeutic dose of Tiotropium bromide and Salmeterol xinafoate, respectively, a concentration-dependent degradation of both active drug substances was observed. The degradation rate of Salmeterol xinafoate was found to be on a higher level and, therefore, needed special consideration. Surprisingly, it was found that the variability of the delivered drug dose out of the capsule is also dependent on the fill weight of the capsule. This finding is an un-expected result and has not yet been reported in the scientific literature. Surprisingly, it was also found that the dose variability is fairly stable during storage when a certain capsule fill weight is selected.

In summary, there are three un-expected elements:

Firstly, it is known from the literature that a higher level of homogeneity in powder blends can be obtained with increasing drug content in the powder blend. Surprisingly, it was now found that a higher level of homogeneity (expressed as % CV of the delivered dose results) was obtained when lower drug content is used in the prepared powder blends. In addition, it was found that storage of said optimized formulation did not affect the delivered dose uniformity upon storage, which could also not be expected as opposite results are published in the literature for the fine particle dose variability.

19

Secondly it was found that the blend containing a combination of two active drug lower delivered dose variability as a commercialized product with a single active drug substance but used at the same concentration level (72.5 μg per 12.5 mg powder blend) as the investigational blends.

Thirdly, the optimized powder formulation containing Tiotropium bromide and Salmeterol xinafoate at the desired concentration levels was found to exhibit sufficient chemical stability to make it utilizable in a drug product.

Finally, it is the combination of all these findings that make the developed drug formulation containing Tiotropium bromide and Salmeterol xinafoate in a blend with Lactose monohydrate unique (“novel”) in its composition and inventive, as the reported findings for the optimized formulation could not be expected from the current knowledge of a person skilled in the art.

In view of the above, it is respectfully submitted that the prior art cited by the opponent, alone or in any combination, does not provide the skilled person with the information to solve the above-stated problem and arrive at the teaching of claim 1. Accordingly, the Opponent’s representation against the application under this ground is not maintainable and ought to be rejected.

I find that various cited documents clearly disclose or teaches all the features of the claimed invention and invention consist merely in the succession of a combination of known features, which does not give rise to an inventive functional interaction. Now let me reproduce final claim1: “A capsule, containing an inhalable powder comprising tiotropium 1' and from 0.363% by weight to 0.508% by weight of salmeterol xinafoate 2, which 2 has a melting point of about 124°C, in a mixture with a physiologically acceptable carrier, wherein said capsule contains from 8 to 12 mg inhalable powder.”

PCT application WOOO/28979, published on 25.05.2000 and its equivalent US Patent 6645466 discloses “a dry powder formulation for inhalation” preferably comprising magnesium stearate to improve moisture resistance, a betamimetic, 20

and/or

an

anticholinergic,

and/or

a

corticosteroid

in

the

form

of

a

pharmaceutically acceptable salt or ester, wherein suitable betamimetics include

salmeterol

xinafoate, and

suitable anticholinergics include

tiotropium bromide. The typical active concentration in the formulation can be approximately 0.1-10% by weight,in particular 0.1-5% by weight based on the total formulation . Inhalable dry powders are known to be stored in pre-dosed units, such as capsules and blister packs and that the use of magnesium-stearate containing formulations is suitable for improving the resistance to moisture of predosed units, for example, in the form of capsules. The active agents to be inhalable these must be obtained having a particle size of approximately 1 - 1 0 microns, preferably 1-6 microns, which can be obtained by conventionally known techniques, such as controlled precipitation, micronization, or by spray drying. Suitable carriers include mono- or disaccharides, such as glucose (i.e. a monosaccharide), lactose (i.e. a disaccharide), lactose monohydrate, sugar alcohols, etc., wherein lactose monohydrate is particularly preferred. US Patent 5795594, [published on 18th August, 1998] teaches salmeterol xinafoate polymorph with a melting point of about 123.5 °C [peak heat flow from 119.94 to124.3 °C] with and having bulk density

0.137g.cm~3 [which is

closer to0.134 g.cm’3].

WO/0069468 and its equivalent granted Indian patent 211375

teaches an

inhalable pharmaceutical composition comprising

salt

salmeterol

and

tiotropium salt.

WO02/38154

and

its

Equivalent

Canadian

application

CA

2429012

discloses a capsule containing an inhalable powder formulation comprising salmeterol sulfate and tiotropium bromide with a total inhalable powder fill of 5mg. Application also indicates the use of

salmeterol xinafoate.

US application US 20020179087 teaches a capsule containing inhalable powderd formulation comprising

salmeterol

xinafoate

and

oxitropium

bromide

and lactose (disaccharide carrier) with a powder fill of 12.5mg wherein the

21

proportion of salmeterol xinafoate in the inhalable powder is 0.4% by mass of the total mass of the inhalable powder inside a capsule,

US application 2002/0189610 teaches a capsule containing inhalable powder formulation comprising salmeterol xinafoate and ipratropium bromide wherein the proportion of salmeterol xinafoate in the inhalable powder is 0.4% by mass of the total mass of the inhalable powder inside a capsule.

Applicant claimed that the optimized formulation powder as claimed has resulted in to improved stability and more even disability. After going through the specification it is observed that the application 2632/DELNP/2005 do speak about optimization of parameters to prepare a formulation such as "high stability of the active substance in grinding process is absolutely essential”, “the active substance used to prepare the pharmaceutical compositions mentioned above should be as pure as possible”, “ stability during long term storage should be guaranteed under a variety of ambient conditions”, "uniform distribution of the drug in the formulation is also a critical factor" ,”polymorphic changes grinding process”, “choice of excipients”,” good flow properties”, good emptying characteristics of the capsules”,”high degree of homogeneity of the powder mixture”,

However, no experimental data with respect to the analysis of the inhalable powder so as to show that how this optimized powder has shown improved results on various parameters stated above.

In the absence of any data as regards the purity, long term stability, homogeneity and dispersion of the active ingredients in the powder, quantitative measure of flow property of the inhalable powder, it is not possible to ascertain any inventive technical contribution and these appears to me as mere statements whereas all inventive technical features of the claimed invention are already disclosed in the cited documents.

I agree to the contention of opponent that one of the supposedly 'most unique' characterizing feature, the specific melting point of the powder or one of the 22

active ingredients, has not been even been mentioned in any of the exemplified formulations as a property of salmeterol xinafoate or that of the powder taken as a whole and there is no mention of this feature and its significance in the body of the specification or even in the test data provided by Dr. Steckel.

I am also not able to ascertain that how this particular characterizing feature of melting point of one of the active ingredients or of the powder taken as a whole helps attain the objectives as enunciated or how it solves the problems enunciated has not been provided anywhere in the specification. It is further difficult to ascertain in absence of data that when the active substances when subjected to high stress on surface of the crystals coupled with input of energy during the grinding process and micronization undergo polymorphic changes, how the stability of the particular crystal form of salmeterol xinafoate shall be affected. Although Applicant tried to differentiate his invention with respect to cited documents, but no difference in terms of contribution by the claimed invention over the parameters and features discussed above has been brought before me by the Agent for Applicant.

I strongly condemn the argument of the applicant that opponent has lifted arguments on inventive step from the observations in the International Preliminary Examination Report and from the official letters of the corresponding applications of the US applications and mainly based on the prior art documents cited therein. How does it matters, from wherever the arguments lifted from, if they have a relevance and vital to meet the ends of justice.

I can not ignore that the even the International Preliminary Examination Report issued in respect of the corresponding PCT Application has declared the subject matter of the 2632/DELNP/2005 application to be obvious. Furthermore, all the claims of the corresponding US application 20040152720 have been rejected before the abandonment of the application on the grounds of being obvious. Similarly, the claims made in another corresponding application US 2007 0128125 have also been rejected in a non-final rejection based on similar ground. It

23

doesn’t matter whether it is non-final one because as of now this non- final rejection is only final one and has merit in itself.

I abide by the honourable Supreme court principle as laid down in AIR 1981 SUPREME COURT 1444, Patents Act (39 of 1970), S.2 (1)(j), S.64, which is as follows:

“ It is important that in order to be patentable an improvement on something known before or a combination of different matters already known, should be something more than a mere workshop improvement; and must independently satisfy the test of invention or an 'inventive step'. To be patentable, the improvement or the

combination must produce a new process or improved

results. Mere collection of more than one integers or things not involving the exercise of any inventive faculty, does not qualify for the grant of a patent.”

In view of above, I conclude that claimed invention and so do the claims lacks inventive step. Therefore, this ground is hereby maintained.

Non- Patentable subject matter Section 25(1) (f): That the subject of any claim of the complete specification is not an invention within the meaning of this Act, and is not patent able under this Act. Section 3 (d): The mere discovery of new form of a known substance which does not result in the enhancement of the known efficacy of that substance or the mere discovery of any new property or mere new use for a known substance or of the mere use of a known process, machine or apparatus unless such known process results in a new product or employs new reactant. Opponent submitted that the inhalable powdered combination of salmeterol xinafote and a titotropium salt as claimed is merely a combination of new forms of known substances, having known properties and for known uses: Furthermore, there is no mention about the enhancement in efficacy of the said combination with respect to the known combination, let alone its own efficacy. It is therefore respectfully submitted that the alleged invention as claimed in claims is not an invention within the meaning of section 3 (d) of the Act.

24

The subject matter of claims of the 2632/DELNP/2005 application falls under non-patentable subject matter u/s 3(d) of the Act for one or more of the following reasons. •

The subject matter of claims pertains to a capsule formulation of a known

combination of known pharmaceutically active ingredients salmeterol Xinafoate and a tiotropium salt. •

One of the pharmaceutically active substances namely salmeterol xinafoate that

is used in the claimed composition of the 2632/DELNP/2005 application is merely a new form of a known substance characterized by a melting point, bulk density and an XRD pattern while the other pharmaceutically active ingredient is admittedly a known substance. •

No where in the 2632/DELNP/2005 specification, it is suggested, indicated and

substantiated that the use of the characterized salmeterol xinafoate form results in increased biological activity or enhanced therapeutic efficacy in comparison with the biological activity and therapeutic efficacy as shown by the known and reported form of salmeterol xinafoate.

•

Synergistic effect exhibited by the composition because of the combination of

the active ingredients irrespective of their physical forms is admittedly known (see page 1 last paragraph of the 2632/DELNP/2005 specification) WOOO/69468 is

cited

by

the applicants for a synergjstic combination of salmeterol xinafoate and tiotropium bromide) In the matter of Novartis Vs Controller general of Patents and Designs, the Madras High court, held that: ... "It (Section 3(d)) only declares that the very discovery of a new form of a known substance which does not result in the enhancement of the known efficacy of that substance, will not be treated as an invention. The position therefore is, if the discovery of a new form of a known substance must be treated as an invention then the patent applicant should show that the substance so discovered has a better therapeutic effect."

25

“Borland’s medical dictionary defines the expression efficacy in the field of pharmacology as "the ability of a drug to produce a desired therapeutic effect" and efficacy is independent of potency of the drug. Dictionary meaning of Therapeutic is "healing of diseases- having a good effect on the body". Going by the meaning for the word "efficacy" and therapeutic extracted above , what the patent applicant is expected to show is, how effective the new discovery made would be in healing a disease / having a good effect on the body ? In other words, the patent applicant is definitely aware as to what is the therapeutic effect of the drug for which he had already got a patent and what is the difference between the therapeutic effect of the patented drug and the drug in respect of which patent is asked for. Therefore there is simple exercise of, though proceeded by research, we state - for any patent applicant to place on record what is the therapeutic effect/efficacy of a known substance and what is the enhancement in that known efficacy". It is further submitted that the applicant has not provided any data whatsoever which proves any enhancement in efficacy. It is sincerely submitted that the alleged improvement which- constitutes the subject matter of the 2632/DELNP/2005 application is directed to optimization of parameters to prepare a formulation comprising a known combination of active substances except for the fact that one of the active substance is in the form of a particular known polymorph (which is merely a new form of known substance). It is particularly emphasized that neither the so-called optimized formulation contributes to healing of the disease nor does it help in having a good effect on the body. No such comparative data that substantiates the enhancement in efficacy as compared to the earlier known inhalable powder formulations comprising the same active substances is provided in the 2632/DELNP/2005 application. Therefore, the subject matter as claimed in the 2632/DELNP/2005 application is not -patentable and is liable for rejection u/s 25(1) (f) read with 3(d).

Applicant submitted that the provisions of section 3(d) of the Act are not attracted. The applicant's invention is directed to a capsule comprising an inhalable powder with improved stability, which does not fall within the purview of Section 3(d).

26

Applicant further submitted that the term 'enhanced efficacy' is one unique to Indian patent law and as such it cannot be expected that explicit disclosures in respect of such enhanced efficacy be present in the specification more so in view of the fact that the present application is a national phase application. Accordingly, the ground of opposition is not sustainable and is liable to be rejected.

Applicant also submitted that the Opponent submitted that the claimed invention falls within the provisions of Section 3(d) and quoted a recent Chennai High Court decision, which enunciates the applicability of the said Section. It is clarified that the matter is sub-judice in this context and that the Section 3(d) is not attracted.

After going through the specification and prior art documents, submissions and evidence, I find that claims of this instant application pertains to a capsule formulation

of

a

known

combination of known pharmaceutically active ingredients salmeterol Xinafoate and a tiotropium salt and one of the pharmaceutically active substances namely salmeterol

xinafoatethat

2632/DELNP/2005

is

used

application

in

the

is

claimed merely

composition a

new

of

the form

of a known substance characterized by a melting point, bulk density and an XRD pattern while the other pharmaceutically active ingredient is admittedly a known substance. No where in the 2632/DELNP/2005 specification, it is suggested, indicated and substantiated that the use of the characterized salmeterol xinafoate form results in increased biological activity or enhanced therapeutic

efficacy in comparison with the

biological activity and therapeutic efficacy as shown by the known and reported form of salmeterol xinafoate.

No such comparative data that substantiates the enhancement in efficacy as compared to the earlier known inhalable powder formulations comprising the same active substances is provided in the 2632/DELNP/2005 application.

27

I am abiding by the hon’ble Madras High court, In the matter of Novartis Vs Controller general of Patents and Designs, held that: ... "It (Section 3(d)) only declares that the very discovery of a new form of a known substance which does not result in the enhancement of the known efficacy of that substance, will not be treated as an invention. The position therefore is, if the discovery of a new form of a known substance must be treated as an invention then the patent applicant should show that the substance so discovered has a better therapeutic effect."

In view of above I state that the subject matter for application no. 2632/DELNP/2005 is not patentable under section 3(d)

Section 3 (e) A substance obtained by a mere admixture resulting only in the aggregation of the properties of the components thereof or process for producing such substance. Opponent submitted that invention as claimed relates to a substance which is an mere admixture of two known active in a known way therapeutic agents namely a salt of tiotropium and Salmeterol xinafoate in a powdered form meant for inhalation It is therefore that subject matter as claimed falls under non patentable subject matter u/s 3 (e)

Applicant submitted that the Opponent only made a vague statement that the applicant’s invention falls under Section 3(e) as it comprises a mere admixture of known substances in a known way. The applicant reiterated the submission made in the reply statement and submitted that the applicant’s invention is directed to an inhalable powder powder comprising the components as disclosed in the main claim. It was also brought to the attention of the learned Controller that the weight percentages of the components have been disclosed in the main claim itself. The Opponent’s contention is therefore wrong and misplaced. After reading the specification and prior arts, it is beyond doubt that salt of tiotropium and Salmeterol xinafoate as established on other granted patents that this composition exhibits synergistic effects and which is beyond mere aggregation of the properties.

28

Consequently, this salt of tiotropium and Salmeterol xinafoate in a powdered form meant for inhalation is not a mere admixture of two known active substances in a known way. Therefore this ground of opponent is not maintainable and hereby rejected.

Disclose the Information u/s 8 to the Controller

Section 25(1) (h): that the applicant has failed to disclose to the Controller the information required by section 8 or has

furnished the information which in any

material particular was false to his knowledge. The Opponent pleaded that he was not privy to the details of the corresponding applications of the subject application. The Opponent alleged that information required u/s 8 of the Act was not furnished in time and was incomplete. The Opponent also contended that the ‘Form-3’ filed on February 28, 2008 cannot be taken on record as it has been filed late and there is not provision to take the same on record.

In reply, the Applicant submitted that they has been communicating the details of corresponding applications to the Patent Office on Form-3 along with requisite petitions where applicable and invited the attention of the Controller to Form-3’ filed at the time of filing of the application and ‘Form-3’ filed along with the response to the first examination report on February 28, 2008 The Applicant submitted that the Opponent’s contentions were untenable and there are clear provisions in the Act to take the same on record. Moreover, the ‘Form-3’ filed on February 28, 2008 has been filed with the requisite petition.

I found from the records made available to me that Form 3 u/s 8 of the Act was filed at the time of filing of the Application but without the details of the status of corresponding foreign application. The Applicant further filed form-3 on February 29, 2008 along with petition u/r 137 and paying requisite fee showing status of corresponding foreign filings, which can be allowed.

Therefore this ground of opponent is hereby rejected. 29

Insufficiency of disclosure Section 25(1) (g). That the complete specification does not sufficiently and clearly describe the invention or the method by which it is to be performed.

The Opponent alleged that the description does not sufficiently and clearly define the invention or the method by which it is to be performed. The opponent brought to the notice that no experimental data with respect to the analysis of the inhalable powder so as to show that how this optimized powder has shown improved results on various parameters stated above. Most unique characterizing feature specific melting point 124 degree centigrade has even not been mentioned in any of the exemplified formulations.

The Opponent further argued that most of the examples are not workable in light of the amended set of claims on record.

The Applicant submitted that the original claims encompassed all the examples and the claims were amended to meet the prior art documents cited. The amended claims are supported by examples 8 to 12, 20 to 24 and 32 to 36 of the description as also accepted by the Opponent.

After going through the specification I agree to the Applicant to the extent that specification do describe about the selection of excipient lactose monohydrate , Preparation

of

salmeterol

xinafoate,

moicronisation

of

salmeterol

xinafoate,Micronisation of crystalline titropium bromide monohydrate, x-ray structural alalysis, determining particle size, surface area, enthalpy of solution and examples 1-36 on preparation of the powder formulation according to invention etc. on workability front. But it is agreed that no reference to achieving most unique characterizing feature of specific melting point 124 degree centigrade has been provided in any of the exemplified formulations. The opponent contention regarding no experimental data with respect to the analysis of the inhalable powder so as to show that how this optimized powder has

30

shown improved results on various parameters has already been discussed earlier.

Therefore, specification needs to be described sufficiently to support the claim and this ground is maintained.

Affidavit not in proper format Opponent submitted that the proceedings that took place on 27th March, 2008 were in nature of formal opposition proceedings U/S 25(1). Therefore section 79 read with rule 126 will be applicable to the submitting of evidence in the course of these proceedings. The relevant section 76 and rule 126 are reproduced herein below. Section79. Evidence how to be given and powers of Controller in respect thereof. - Subject to any rules made in this behalf, in any proceeding under this Act before the Controller, evidence shall be given by affidavit in the absence of directions by the Controller to the contrary, but in any case in which the Controller thinks it right so to do, he may take oral evidence in lieu of, or in addition to, evidence by an affidavit, or may allow any party to be cross-examined on the contents of his affidavit. Rule 126(1) The affidavits required to be filed by the Act or the Rules (for preparing evidence) to be filed at the Patent Office or furnished to the Controller should be duly sworn in the manner as prescribed in Rule 126(3) Rule 126(2) "The Affidavits required to be filed by way of evidence under the Act of the Rules should also be confined to such facts as the deponent is able to his own knowledge, to prove, except in interlocutory matters, where statements of belief of the deponent may be admitted, provided that the grounds thereof are given."

Rule 126(3) 31

The Affidavits should be sworn to as follows: In India - before any court or person having by law authority to receive evidence, or before any officer empowered by such court as aforesaid to administer oaths or take affidavits, If any country or place outside India - before a diplomatic or consular office, within the meaning of the Diplomatic and Consular Officers (Oaths & Fees) Act,1948 (41 of 1948), in such country or place or before a notary of the country or place, recognized by the Central Government under Section 14 of Notaries Act,1952 (53 of 1952) or before a judge or Magistrate of the country or place.

Rule 126(4) Alterations and interlineations shall, before an affidavit is sworn to or affirmed be authenticated by the initials of the person before whom the affidavit is sworn.

It appears that the applicant provided some data to Prof. Steckel and Dr. Steckel is providing an opinion on the data supplied by Applicant. The data is therefore not in the personal knowledge of Prof. Steckel and since the applicant is an interested party the question of authenticity of the data is questionable. Therefore, it cannot be said that the opinion is an independent, impersonal and objective opinion. Therefore, firstly even if the document were to be considered as an affidavit under rule 126, the contents of the document, which are other than, fact and which are not to the knowledge of deponent must be expunged and not taken on the record.

It is sincerely brought to the notice of the learned Controller that under the guise of the expert opinion, the applicant has merely made an attempt to substantiate the alleged novelty and non-obviousness of the subject matter as claimed in 2632/DELNP/2005 application on the basis of experimental data set, which is not present in the specification itself. The fact that the applicant is relying on data from experiments which is not provided in the specification [neither in examples nor in the description] for establishing the novelty and non-obviousness of the specification directly implies that the experimental data as provided in the examples and in the specification is not sufficient enough to fully and particularly establish the novelty and non-obviousness of the claimed subject matter. 32

Therefore, either the applicant must admit to the insufficiency of data as provided in the specification or it should establish and substantiate the novelty and nonobviousness of the claimed subject matter of the 2632/DELNP/2005 application solely on the basis of experimental data as provided in the specification itself.

Without prejudice to the submission in the above paragraph, even if the experimental data as used in the supposed expert opinion were to be relied in assessing the novelty and non-obviousness of the subject matter as claimed in the 2632/DELNP/2005 specification, it still falls far short of establishing any significant enhancement in efficacy of the composition claimed, therefore, it is respectfully reiterated that the subject matter of the 2632/DELNP/2005 application is not patentable subject matter u/s 3(d), since it pertains to a combination of merely new forms of known substances without any enhancement in efficacy.

It is also sincerely reiterated that again in the data provided by the applicant to Dr Steckel, it has not made any mention of the particular melting point of salmeterol xinafoate. Dr. Steckel is also silent as to the prior knowledge of polymorph of salmeterol xinafoate with the specific melting point (about 124°C). It is thus respectfully submitted that the Dr. Steckel has not relied on all the documents for assessing the novelty and non-obviousness of the subject matter claimed in the 2632 application. It is for this reason that it is reiterated that the opinion of Dr. Steckel is biased and is unduly inclined in the favor of the applicant.

The Opponent contended that the evidence Prof .Dr. Hartwig Steckel of ChristianAlbrechts University, Gutenberg, Germany, submitted by the Applicant is not an affidavit and therefore cannot be taken on record as evidence. The Applicant refuted this contention and submitted that is the Controller is of the opinion that the affidavit is not in the proper format; an opportunity may be presented to the Applicant to submit the same in the proper format as directed.

The above argument confirms that the Opponent’s contentions are baseless and that the representation filed by the Opponent is frivolous and has been filed merely to delay the grant of the patent.

33

I find that affidavit submitted by the Applicant as evidence by Prof .Dr. Hartwig Steckel of Christian-Albrechts University, Gutenberg, Germany, is duly notarized outside the country and can be considered as evidence. I personally believe that evidence in any form or manner if it helps to meet the ends of justice can be considered. But I agree to the contention of the Opponent that the data provided by the applicant to Dr Steckel, has not made any mention of the particular melting point of salmeterol xinafoate and Dr. Steckel is also silent as to the prior knowledge of polymorph of salmeterol xinafoate with the specific melting point (about 124°C). It is further true that evidence still falls short of establishing enhancement in efficacy of the composition claimed in terms of various parameters discussed in specification. Therefore, evidence of Dr, Seckle does not have much relevance to establish inventive step.

In view of above findings and

the facts on records, the present application

2632/DELNP/2005 is hereby refused to proceed for grant of Patent on the grounds 25(1)(e), read with 2(1) j, and 25(1)(f) read with 3 (d) and 25(1) (g), The application stands disposed off with no cost to either party.

Dated. June 11, 2008

(N R Meena ) Assistant Controller of Patents and Designs The Patent Office, New Delhi.

34