THE PATENTS ACT, 1970 (AMENDED BY THE PATENTS ACT 2005) AND THE PATENT RULES, 2003 (AMENDED

BY THE PATENTS RULES 2006)

In the matter of patent Application no.85/DEL/1995 filed on 23/01/1995

AND

In the matter of opposition by way of representation U/s 25(1) on said application no.85/DEL/1995
Eli Lilly & Co., Lilly Corporate Center, Indianopolis, IN 46285, USA Ajanta Pharma Ltd., Ajanta House, Govt. Indl.Area, Charkop, Kandivili (W), Mumbai 400067, India ....The Opponent The Applicant

Hearing held on 30th MAY 2006

Present: Sh. Sanjay Kumar, Smt Ranjana Mehta Dutt, Smt Richa pandey, Smt Deepa Tikko M/s Remfry & Sagar,Attorneys for the Applicant Sh S Majumdar M/s S. Majumdar & Co.Attorney for the Opponent And Sh Sonewane, Company Secretary, M/s Ajanta Pharma Ltd...The opponent DECISION An application titled as ,Tetracyclic derivatives, process of preparation and use was filed on 23rd January 1995 by Laboratoires Glaxo S.A., 43, Rue Vineuse, 75016 Paris, France for grant of the patent as indicated in the application form filed by their agents, M/s Remfry & Sagar, Gurgaon, NCR, India. The application was assigned to ICOS Corporation, 22021-20th Avenue SE, Bothell, WA 98021, USA as recorded in the Patent

Office, Delhi in December 1997. A change in the name of the applicant from Laboratoires Glaxo S.A to Laboratoires Glaxo Wellcome was recorded in the Patent office, Delhi on 17th February 1998. ICOS Corporation further assigned rights to M/s Eli Lilly & Co., Lilly Corporate Centre, Indianapolis, IN 46285, USA and recorded change of applicant in the Patent office on 29th August 2003. Thus presently on record the applicant is M/s Eli Lilly & Co. The application claimed priority of UK application no. 9401090.7 dated 21st January 1994. The present application was filed u/s 5(2) of the Patents Act, 1970. The application was also filed for grant of EMR (EMR/3/2003) granted on 26th August 2004. The application has been published u/s 11(A) of the Act on 4th March 2005 in the VIIth volume of the Patent Office journal, page 8408. However, later to this the EMR ordered as no effect should be given to EMR certificate issued on 26/8/2004 without the leave of the court by the Hon' High court of Kolkatta on a WP no. 2075/2004 and T no. 359/2004. This order was notified in Gazette of India, part III, section 2 on November 27, 2004. The order is effective till date. The application relates to tetracyclic derivatives of formula I, sub groups of compounds of formula I, its isomers and tautomers, pharmaceutically acceptable salts and metal salts, individual compounds of formula I and pharmaceutical composition comprising the compound of formula I. The application also discloses processes for preparation of compounds of formula I and its individual compounds and method of treatment of various ailments by the use of compound of formula I. It is disclosed that the tetracyclic derivatives of formula I are potent and selective inhibitors of cyclic guanosine 3, 5monophosphate specific phophodiesterase (cGMP specific PDE). Thus compounds of formula I are useful for treatment of such conditions where inhibition of cGMP specific PDE is thought to be beneficial, including treatment of cardiovascular disorders. Various use of the tetracyclic derivatives of formula I has been disclosed in page 2 and 7 to 10 of the complete specification. No prior art of the claimed invention has been discussed in the application. The application as filed had 16 claims. Claims 1 to 11 (product claims) pertained to the compound of formula I and its isomers, Claims 12, 13 and 14 pertained to the use of the compound, method of treatment by the compound and pharmaceutical composition

comprising the compound of formula I, respectively. Claim15 (product claim) related to the intermediates in the preparation of compound of formula I. Claim16 pertained to the omnibus claim of the compound of formula I. Later on the applicant added 44 claims voluntarily by applying in prescribed manner on 7th January 2003. The application came up for examination and first examination report was issued on 12th April 2005. The application as examined had 60 revised claims. The added claims 16 to 57 pertained to processes of preparation of the compound of formula I and claims 58 to 60 pertained to omnibus claims of the process and product. The examiner raised objections on the grounds of non-patentability u/s 2(1)(j), 3(i), 3(e) and 3(d), conflicting claims with the claims of 792/DEL/1999 and non-allowability of product claims as the compound was invented prior to 1995 and this application was filed under WTO category. In reply, the applicant made amendments and the number of claims were reduced to 28. Presently the claims 1 to 7 relate to the tetracyclic derivatives of formula I, claims 8 to 10 relate to its isomer, claims 11 to 25 relate to the process of preparation of the tetracyclic derivatives of formula I and its cis isomer and claims 26 to 28 are omnibus claims of the compound, its isomer and process of preparing the isomer. A pre grant opposition by way of representation was filed by Ajanta Pharma Ltd. u/s 25(1) of the Act on 30th January 2006. The opponent filed a revised opposition on 30th March 2006 which included an expert evidence of Dr Nityanand. The reason for filing revised opposition was stated that the original representation dated 30/1/06 was based on the corresponding US patent application because the specification as published in India was not available during the filing of the earlier representation. In the interest of justice, the revised representation was taken on record by the office. The applicant filed a reply statement u/r 55(4) of the Patent Rules, 2003 on 2nd March 2006 and a revised reply statement was filed on 28th April 2006 to contest the revised opposition of the opponent with the prayer that the revised representation may not be taken on record. The opponents in view of prayer of applicant that the revised representation, which is containing expert evidence, should not be taken on record filed an interlocutory petition on 25th May 2006 to take their evidence on record. The applicant opposed on 26th May 2006, the interlocutary petition and such allowance of revised opposition dated 30/3/2006 including

an evidence of Dr Nityanand, due to absence of any such provision in the Patent law. However, in the interest of justice and keeping in view the basic intent of section 25(1) of the Patent Act, 1970 i.e. to help the controller in allowing the valid patent, I take the said revised opposition with evidence on record filed by the opponent. The said evidence of the opponent serves as evidence in support of grounds of opposition for deciding the validity of the claims of the present application. To arrive on my abovesaid conclusion, I rely on 49 RPC 565 as detailed below. In his decision the Controller disregarded the publications on the ground that they were inadmissible at this stage. The opponent appealed to the Law officer- Held, that the Comptroller is bound in the public interest to consider any alleged prior publication which may be brought to his notice after the hearing and before the issue of his decision. Opponents raised various issues in their representation and argued the various grounds of opposition at length. The grounds taken up in the representation are as under 1. Prior publication 2. Prior claiming 3. Prior public knowledge or prior public use 4. Lack of Inventive step 5. Not an invention u/s 2(1)(j), 3(d), 3(e), 3(i) 6. Insufficiency of description 7. Non disclosure regarding foreign filing of the invention During the hearing, the opponents withdrew 1st, 2nd and 7th grounds. Now I shall discuss each remaining issue in details herein below. 1. Lack of Inventive step The opponent has cited and relied upon the following two documents to show that the claims of the present application are obvious.

(i) US 3,917,599 dated 4th Nov 1975 (Exhibit 1) (ii) Journal of Medicinal Chemistry, 1973, Vol 16, No.5, pages 561-564 (Exhibit 2) The opponent has also furnished an expert evidence of Dr Nityanand in respect of obviousness supported by Exhibit 3 (Indian Journal of Chemistry, Vol 11, May 1973, pp-417-421 by Anil Kr Saxena et al.), Exhibit 4 (Synthesis from dltryptophan and aldehydes, Jan 1948) and Exhibit 5 ( Journal of American Chemical Society, 1980, 102, 6976-6984). Exhibit 1 relates to 2-substituted-1,2,3,4,6,7,12,12a-

octahydropyrazino[2,1:6,1}pyrido[3,4-b] indoles that corresponds to formula I(E) where Z and Y = H,O ; R2 = H, lower alkyl group ; X = straight or branched chain alkylene group optionally interrupted by a CO or CHOH group ; R = H, lower alkyl, aryl, aryloxy, cyano, carboxy, dialkylamino, benzodioxanyl or 4-pyridyl and X and R may together be H.. The Opponents in their statement has tried to point out similarities between the process for preparation of compound of formula I of present invention and compounds as disclosed in Exhibits 1 and 2. The process steps followed in exhibit 1 are (i)Condensation of dl-tryptophan with aldehyde to yield formula II, (ii)Condensing formula II with acetyl chloride to yield formula V, (iii) Condensation of formula V with primary amines to yield compounds of formula I. The opponent alleges that the steps (i) and (ii) are same as that of the process disclosed in the instant application. In step (iii) the compounds of formula I of instant application differs from compounds of formula (I ) of exhibit 1 only in the presence of substituent R2 on the pyrazino pyrido indole ring where R2 is optionally substituted monocyclic aromatic ring selected from benzene, thiophene, furan, pyridine or optionally substituted bicyclic ring attatched to the rest of the molecule of the formula I via one of the benzene ring carbon atoms and wherein the fused ring A is a 5,6 membered ring which may be saturated or partially or fully unsaturated and comprises carbon atoms and optionally one or two hetero atoms selected from O, S and N. The above process essentially employs the same starting material (dl-tryptophan and aldehyde) to yield same intermediates as that of the process of the instant application.

The opponent has compared the structure of the compound claimed in the instant application with the compound as disclosed in exhibit 1 and has shown that the said two compounds differs only in the presence of R2 substituent on the pyrazino pyrido indole ring. The opponent alleges that the claimed compound of formula I is mere substitution of groups in the generic compound of Exhibit 1, that is obvious to a person skilled in the art. The opponent further has compared the use of the compound of the instant application to that of the exhibit 1. The compounds of exhibit 1 has strong tranquilizing and hypotensive activities and are used to treat cardiovascular disorders. The compounds of the instant application are potent and selective inhibitors of cyclic guanosine 3, 5monophosphate specific phosphodiesterase having various therapeutic utilities including the treatment of cardiovascular disorder. The opponent points out at example 122 in the specification of the instant application which shows the hypotensive effects of formula I. According to the opponent a case of obviousness can be made when chemical compounds have very close structural similarities, can be prepared by same process steps and have similar utilities. Different uses of the claimed compound are obvious extension over the prior art. Changing a substituent group in the claimed class of compound would still render the compound as obvious and not a subject matter of subsequent patent. The opponent argues that upon the expiration of the patent referred as Exhibit 1, the public should be free to use not only the claimed invention but also the obvious modifications or variants of the invention. Hence, the opponent states that the applicants compound is obvious with respect to exhibit 1 and lacks inventive step. Exhibit 2 (Article by Saxena et al, Journal of Medicinal Chemistry, 16(5), 1973, 561-564 entitled,Agents acting on CNS) relates to the synthesis of 1,2,3,4,6,7,12,12aoctahydropyrazino[2,1:6,1}pyrido[3,4-b] indoles, a ring system which incorporates both tryptamine and piperazine. The Opponents in their statement has compared the process claimed in the instant application with the process as disclosed in exhibit 2. The process steps followed in exhibit 2 are

(i) Cyclization of dl-tryptophan (starting material) with formaldehyde followed by esterification yields dl-methyl 1,2,3,4-tetrahydro-9H-pyrido [3,4-b] indole-3-carboxylate, formula (a), (ii) Condensation of formula (a) with chloro acetyl choride yields dl-methyl-2chloroacetyl-1, 2,3,4-tetrahydro-(H-pyrido[3,4-b]-indole-3-carboxylate of formula (b), (iii) Reaction of formula (b) with diethylaminoethylamine gives dl-2-(betadiethylaminoethyl-1)-1,4-dioxo-1,2,3,4,6,7,12,12-octahydropyrazino [2,1: 6,1] pyrido [3,4-b] indole, formula (c ), (iv) Formula (c ) on LiAlH4 reduction gives the compound (Ia). The opponent alleges that the steps (i) and (ii) are same as that of the process disclosed in the instant application. In step (iii) secondary amines are used instead of primary amines as used in instant application. The compounds of formula I of instant application differs from compounds of formula (c ) of Exhibit 2 only in the presence of substituents R1 and R2 on the pyrazino pyrido indole ring, R1 being diethylaminoethyl substituent and R2 being hydrogen. The opponent states that the process disclosed in exhibit 2 essentially employ the same starting material i.e. dl-tryptophane, formula IV of the instant application. Formula III and formula II of the instant application are same as formula (a) and formula (b) respectively of exhibit 2. The only difference in the process disclosed in the instant application is reacting formula II with primary amines to make the same generic compound as disclosed in prior arts Exhibit 1 and 2. The opponent has quoted Ex parte A, 17 USPQ2d 1716 (Bd. Pat. App. & Inter. 1990) (Annexure I) The opponent argued based on the above judgment that the class of compounds claimed by the applicants is a mere substitution of groups on the generic compound (intermediate compound, formula (c ) of Exhibit 2) and thus an obvious extension of teachings of prior art as disclosed in Exhibits 1 and 2. The applicant has denied the ground of obviousness and argued that the process of the Exhibit I has not been claimed in the present application. The claimed compounds are not

produced from formaldehyde but from an aldehyde having different structure from any aldehyde disclosed in exhibit 1. The applicants stated that the single compound tested in Exhibit I (column 8, line 30 through column 9, line 36) does not have similar structure and differs in three ways from the presently claimed compound i.e. (i) A substantial difference exists at the R2 position of the compound, (ii) the sole compound tested is free of oxo groups in the tetracyclic ring structure, (iii) corresponding R1 group of the tested compound is not encompassed by the presently claimed R1 groups. The compounds of Exhibit 1 contains an R1 group that corresponds to the R2 group of the claimed compounds and an X-R moiety that corresponds to the R1 group of the claimed compound. The applicant pointed that in the broadest disclosure, R1 of compounds of Exhibit 1 is H or a lower alkyl group and X-R is an alkylene group, optionally containing CO or CHOH (i.e. X), bonded to hydrogen, lower alkyl, aryl, aryloxy, cyano, carboxy, carbalkoxy, dialkylamino, benzodioxanyl or 4-pyridyl (i.e.R) or X-R is H. The presently claimed compounds contain a cyclic aromatic R2 group that is substantially different from the R1 group of the compounds disclosed in Exhibit 1. The applicants denied the strong hypotensive effects of the compounds of Exhibit 1 and invited the attention of tribunal towards column 9, lines 28-30 of Exhibit 1 which states that compound produced no significant effect on blood pressure or respiration. The applicant argued that the opponent has not pointed out any test in Exhibit 1 using a compound having a structure similar to the presently claimed compound. Regarding Exhibit 2, the applicant argued that the compounds of Exhibit 2 and the presently claimed compounds do not have similar structure viz. (i) substantial difference exists in both R1 and R2 groups, (ii) compounds of Exhibit 2 are free of oxo groups on the ring structure. The Exhibit 2 discloses compounds having only an H at the R2 position of the present claims and an R group corresponding to R1. The applicant stated that the Exhibit 2 contains three compounds (compounds 10, 13 and 14) having an R1

group being lower alkyl, but these compounds either lack activity (10) or are depressants (13,14). Further the applicant argued that the presently claimed compounds are not produced from formaldehyde. Also the tested compounds of Exhibit 2 differ greatly in activity. Therefore, due to unpredictability of the compounds to provide a specific pharmacological effect, a person skilled in the art could not anticipate the activity of tested compounds, let alone the activity of compounds in a different class of compounds i.e presently claimed di-oxo compounds. The applicant argued that Exhibit 2 fail to suggest or provide any motivation to modify the disclosed compounds to arrive at the presently claimed compounds as a whole in addition to the fact that Exhibit 2 shows that the art is quiet unpredictable. The applicant invited the tribunals attention to Table 1, Gross effects and Remarks columns and page 561 of Exhibit 2. The applicant stated that the Table 1 shows that very minor changes in the R group results in substantial changes with respect to the activity of the compounds, including a change to inactivity. Very few compounds demonstrated hypotensive activity and this activity is disclosed as mild (page 562-563, Exhibit 2). Further, the applicant submitted that an important feature of the presently claimed compounds is the existence of two stereo centers. The Exhibits 1 and 2 do not teach or suggest how to provide a compound having the correct stereochemistry at the carbon atom of the R2 group. The compounds disclosed in Exhibit 2 have hydrogen at this position, which completely eliminates this asymmetric carbon atom. The applicant stated that one must examine the invention as a whole, rather than looking at a snapshot of segments found in the reference and drawing a conclusion. The applicant also stated that anticipation exists only when the disclosure of a single prior art reveals every element of claimed invention. During the hearing, the opponent drew the attention of the tribunal to the affidavit filed by Dr Nityanand, who has opined that the presently claimed compounds are obvious in view of disclosure of Exhibits 1 and 2. The opponent stated that according to the

affidavit, Pfizer conducted studies in the year 1986 and discovered the anti hypertensive effects of Viagra (sildenafil citrate). Later in 1992 Viagra was used to treat erectile dysfunction. Sildenafil citrate acts by inhibiting PDE5 and thereby maintaining high concentrations of cGMP. The presently claimed compounds are also potent and selective inhibitor of cGMP specific PDE having utility in variety of therapeutic areas including treatment of cardiovascular disorders. Therefore, it is evident form the evidence filed by the opponent that the drugs that inhibit PDE5 may share both properties of anti hypertensives and treatment of erectile dysfunction. Exhibit 1 also discloses that the same class of compounds are useful to treat hypertension. Dr Nityanand also pointed out in his affidavits that distribution of stereocenters and R2 substitution in generic compound as claimed in Exhibit 1 is obvious derivatization to obtain compound of the present invention as discussed in the prior art disclosures submitted as Exhibits 3, 4 and 5. According to him, when a claim recites an invention in generic terms, the disclosure of a specific example within the definition of the generic claim anticipates and/or obviates the generic claim.There is nothing on record to dispute the expertise of Dr Nityanand in the relevant field of technology. Furthermore, the applicants did not have any material arguments or evidence to dispute the opinion of Dr Nityanand. During the hearing, the opponent drew attention of the tribunal to Exhibit 1, lines 1-3, column 2, which states that the compounds of this invention have useful biological activities, in particular, strong tranquilizing and hypotensive activities. The opponent also quoted paragraphs bridging columns 3 and 4, which specifically teaches the stereo chemical configuration at the asymmetric centers. The opponent relied upon the following decisions to argue their point during hearing Decision of the Technical Board of Appeal T 882/94 (para 4.4.3) where it is stated Where it is obvious from the state of the art that is certain measure will bring about an improvement of a certain property, a surprising degree of this improvement cannot make this per se obvious measure non obvious. Decision of the Technical Board of Appeal of the EPO T 913/94 where it is stated -

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If the manifestations of the second more serious disease are known to run through the manifestations of the first disease and this assumption reliably substantiated was not confuted, then the activity of the medicament against the more serious disease would already strongly suggests an effect also against the other less serious one. Decision T 20/81 and T197/86 collectively states In order to render the alleged advantages relevant to the definition of the problem underlying the invention, said advantages should be supported by sufficient evidence where comparison is made with highly pertinent prior art and that in case where comparative tests are chosen to demonstrate an inventive step, the nature of comparison with the closest state of art must be such that the effect is convincingly shown to have its origin in distinguishing feature of the invention. For this purpose, it may be necessary to modify the elements of comparison so that they differ only by such a distinguishing feature. The opponent also drew attention of the tribunal to references Bishwanath Prasad Radhey Shyam v. M/s Hindustan Metal Works, Supreme court (para 23) which states as under It is importatnt to bear in mind that in order to be patentable an improvement on something known before 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. I have perused through the invention as claimed in the instant application and the disclosure in the documents cited by the opponent including the documents cited by Dr Nityanand in his affidavit alongwith the arguments made by both the parties. Following differences have been shown by the applicant between the claimed compounds of the instant application and the compounds disclosed in documents cited by the opponent i.e

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(i) different R1 (ii) different R2 (iii) no compounds with oxo group in USP599' demonstrated in the working examples (iv) difference in pharmaceutical properties i.e claimed compound of the instant application has more enhanced pharmaceutical effects (v) stereochemical differences at the Carbon atoms i.e presence of assymetric carbon atoms. I have observed after going through all the documents that the R0, R1 and R3 substituent of the presently claimed compounds overlap substantially with the compounds disclosed in Exhibit 1. I agree with the opponent that there are minor variations in the R0, R1 and R3 substitutions which are obvious and workshop improvements in the generic tetracyclic compounds as claimed in Exhibit 1. The said modification may be easily carried out by the scientists having ordinary skill in the art as there routine scientific trials. The major distinctive substitution indicated by the applicant is that of R2 which has been stated to be a major cause of improvements in the properties of the claimed compound as compared to the compound of the prior art. In this connection, I agree with Dr Nityanands affidavit substantiated with the Exhibits 3 4 and 5 that clearly shows that the R2 substitution is obvious. The R2 substitution is achieved by the condensation of tryptophan with appropriate R2CHO (an aldehyde containing desired R2 group). Citations enclosed with the affidavit as Exhibits 3,4 and 5 clearly shows that incorporating R2 is an obvious extension of a compound of Exhibit 1 (USP599'). Further I find that teachings of Exhibit 1 clearly encompass oxo-free compounds including mono and di-oxo compounds. The above said derivatisation or modification of a known generic molecule may be considered to have an inventive step if any unexpected or significant change has been developed by in the properties of new molecule with respect to its utility. However the opening statement of the instant specification (renumbered page 2) reveals, invention relates to tetracyclic derivatives which are potent and selective

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inhibitors of cyclic guanosine 3',5' monophosphate specific phospho diesterase (cGMP specific PDE) having utility in varieties of therapeutic areas where such inhibition is thought to be beneficial, including cardiovascular disorders. Further on renumbered pages 7 and 8 of the specification, it is disclosed as a consequence of the selective PDE5 inhibition exhibited by the compounds of the present invention cGMP levels are elevated, which in turn gives rise to beneficial....... Thus it is clear from the above-mentioned discussion that all the therapeutic activity of the compound is due to its characteristic of cGMP specific PDE5 inhibition. It is further clear from the disclosure in Exhibit 1, 2 and affidavit sworn in by Dr Nityanand as expert evidence, including the history of 'sildenafil citrate-ViagraTM' that the drugs which inhibits cGMP specific PDE5 are found to be useful as antihypotensive, treating erectile dysfunction as well as cardiovascular disorders. Inference drawn is the tetracyclic derivatives as disclosed in exhibits 1 and in the instant application are having the same inhibitory properties for cGMP specific PDE5 and therefore can treat all related diseases. Therefore it appears no improvement in the properties of the compound as claimed in claims 1 to 10 of the instant application resulting out of further derivatisation of the tertacyclic derivatives of the prior art. It has been observed from the process for preparation of the compound of formula I of the present application that the process steps to obtain the claimed compound are almost similar as that of in exhibits 1 and 2 except some of the variations as are required to insert substituent groups R1, R2 and R3 etc. Such a minor change in the ingredients/reactants and conditions, a reaction leads to only process being inventive but not the resultant product. The new substituent represented as R0, R1, R2 and R3 in the tetracyclic derivative of the present application have been introduced at the known part of the process as disclosed in exhibit 1 and 2, resulting to the said tetracyclic derivative with obvious derivatization and finally obtaining an obvious tetracyclic derivative as represented by formula I of the present application. The present derivative of the tetracyclic compound has been said to have two stereocentres, which was not so in the compounds as disclosed in exhibit 1 and 2. The description on renumbered page 11 of the present application clearly indicates

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that assignment of stereochemistry for formula I is an automatic process depending on selection of material i.e. d or l tryptophan alkyl ester. Thereafter, the assignment of stereo centers of the final compound becomes automatic. The starting material i.e d,l tryptophan alkyl ester of the instant application and of exhibit 1 matches with each other. Therefore, the stereo chemical aspect of compound of formula I of the instant application does not contribute any inventiveness to the compounds of the present invention. Therefore the stereo chemical aspect is an obvious factor in the prior art. As regards the process claim from 11 to 25 and 28 for preparation of the compounds of formula I in the instant application comprise the steps of cyclisation of a compound of formula VIII in an organic solvent and in the presence of reducing agent. The opponent has failed to establish the obviousness in process as claimed in the present application. I have perused through the Exhibit 1 and 2 and find that the process disclosed do not have similar steps as that of the instant application except the starting material and steps are similar in these two processes which has not been claimed by the applicant. It may therefore be inferred that the processes in exhibit 1 and 2 appear to be different from the presently claimed process in claims 11 to 25. Therefore, I agree with the applicants argument that the processes of Exhibits 1 and 2 have not been claimed in the instant application and possess inventive step. Therefore, in view of the above mentioned discussion, I hold that process claims from 11 to 25 and 28 possess inventive step while the claims 1 to 10, 26 and 27 relating to compound of formula 1 is obvious to a person skilled in the art in view of disclosure of the exhibit 1 and 2 read with the expert evidence of Dr Nityanand's affidavit. 2. Prior public knowledge or prior public use The opponent has cited the following two documents to establish this ground (i) US 3,917,599 dated 4th Nov 1975 (Exhibit 1) and (ii) Journal of Medicinal Chemistry, 1973, Vol 16, No.5, pages 561-564 (Exhibit 2).

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The opponent states that the said documents have been in public domain much prior to the date of the instant application. The opponent also states that the process of preparation disclosed in the instant application has been used in India and elsewhere. The applicant has denied the opponents allegations. The applicant argues that the processes disclosed in the references are different as that of the present application and also there are structural differences between the compounds of the references and the claimed compound. I hold that since no document mentioned by the opponent anticipating the present invention in toto and no evidence has been placed before the tribunal by the opponents regarding establishing prior public knowledge and use, the opponents failed to establish this ground. 3. Not an invention/Not patentable The opponent states that the claims pertaining to the process of preparing cis-isomer of formula I represented by formula Ib (claim 26) overlaps with the claim 7 of Indian patent IN183942 and claims 27 to 37 overlaps with claims 8 to 18 of IN183942. The opponent state that IN183942 (77/DEL/95) in the name of ICOS Corporation was filed on 20th January 1995 and have priority of UK dated 21st January 1994. It relates to the process of preparation of tetracyclic beta carboline derivatives. The opponent states that the present invention is devoid of inventive step u/s 2(1)(ja) of The Patent (Amended) Act, 2005 because it is neither a technical advancement over the prior art nor have any economic significance and obvious to a person skilled in the art. The opponent state that the applicants invention is not a new invention u/s 2(1)(l) of The Patents (Amended) Act, 2005 as it is anticipated by publication in any document or used in the country or elsewhere before the date of filing of the application and the present invention is anticipated by publications in exhibits 1 and 2.

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The opponent states that the applicants invention falls u/s 3(d) of The Patents (Amended) Act, 2005 as the present invention is a result of the known process disclosed in exhibit 1 which uses the same reactants. The opponent states that the claim 14 of the instant application falls u/s 3(e) of The Patents (Amended) Act, 2005 as the claimed composition is a mere admixture resulting only in the aggregation of properties of the compound of formula I and pharmaceutically acceptable diluents or carrier and does not show any synergism. The opponent states that the claim 13 of the instant application falls u/s 3(i) of The Patents (Amended) Act, 2005 as the claim discloses a method of treatment using the compounds of formula I in different diseased conditions. The applicants in their reply statement have denied the above said allegations of opponents on these grounds - The applicant states that the process claimed in IN183942 (77/DEL/1995) is different from the process presently recited in claim 11. In context of the economic significance, the applicant drew the attention of the Learned Controller to the product marketed as CialisR that covers the presently claimed compound as active ingredient, for treating male erectile dysfunction. The said product had worldwide sales over USD700 million in 2005. The applicant alleges that the Exhibit 6 dated 20th August 2005 placed by the opponent mentions that Cialis has enjoyed sales of over USD1 billion in less than 2 years and the opponents filing of two representations testifies to the economic significance. The applicant mentioned that the opponent has made a representation against the EMR granted on the present invention on 26th August 2004 before the Honble Calcutta High Court and preferred a writ petition AST No. 1148 of 2004. - The applicants argued that the presently claimed compounds are not a new form of a known substance, but are novel compounds and also does not rely upon a new property or use of an old compound. The claimed processes also result in new product. Because the

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compounds are novel, they cannot use the same reactants as in Exhibit 1. Further the applicant stated that the diseases purportedly recited in claims 11 and 12 are no longer being claimed. Hence, the applicant argued that the presently claimed compounds couldnt fall u/s 3(d) of the Patents (Amended) Act, 2005. - The applicant submitted that the present claims are directed to novel compounds and processes for preparing said compounds. The claims are not directed to composition and the referred claim 14 is no longer in the application. Hence, section 3(e) of the Patents (Amended) Act, 2005 is not applicable. - The applicant submitted that claim 13 is no longer in the application. So section 3(i) of the Patents (Amended) Act, 2005 is not applicable on the instant application. The opponent during hearing alleged that due to discovery by Pfizer regarding use of class of claimed compounds for correction of erectile dysfunction, the economic achievement stated by the applicant is not a surprising phenomenon but a well settled proposition. Further the specification does not mention the use of the claimed compounds for the treatment of erectile dysfunction. I have perused through the claims of the instant application and I find that the applicant has already deleted all such claims, which fall u/s 3(i) and 3(e) during the course of prosecution of the application. Therefore, the ground of opposition u/s 3(i) and 3(e) does not stand. Regarding the claims 1 to 28 falling u/s 3(d) , I conclude that the process claims from 11 to 25 and 28 do have inventive step and may be considered as out of the limits of section 3(d). However the product claims from 1 to 10 and 26 to27 fall u/s 3(d) of the Patents (Amended) Act, 2005. Section 3(d) with the explanation appended to it explicitly states that The mere discovery of a new form of a known substance which does not result in the enhancement of the known efficacy of that substance or mere discovery of any new property or new use for a known substance or of the mere use of a known process,

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machine or apparatus unless such known process results in a new product or employs at least one new reactant. Explanation For the purpose of this clause, salts, esters, ethers, polymorphs, metabolites, pure form, particle size, isomers, mixtures of isomers, complexes, combination and other derivatives of known substance shall be considered to be a same substance, unless they differ significantly in properties in regards to efficacy. The compounds of the present invention are the other derivatives of known substance as disclosed in prior art document US3, 917,599 published on Nov 4, 1975. These derivatives may be considered as same substances as defined in section 3(d) of the Patent (Amended) Act, 2005. The description of the claimed invention in complete specification does not describe anything relevant that can show new derivative differ significantly in properties with the known generic compounds. Therefore claims 1 to 10 and 26,27 are not patentable u/s 3(d) of the Patents (Amended) Act, 2005. 4. Insufficiency of disclosure Opponents states that nowhere in the specification experimental data is given which proves the use of compounds of formula 1 in different diseased conditions. Hence the paragraph 4 of page 7 of the complete specification, which discloses the use of the claimed compound, is hypothetical without any experimental proof. The applicant has denied that the assertions as the utility are unsubstantiated by any data. The applicant stated that the diseases as indicated by the opponents are no longer being claimed and the utility has been well documented at pages 8 and 71 to 77 of the complete specification. To satisfy the tribunal, the applicant has submitted clinical human studies conducted by them, annexed as Exhibit A. These details already form part of the specification in the case of the EMR granted to the present invention where the said

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studies were required to be submitted. The applicants submitted that the same should be considered in these proceedings. In my opinion, though it appears that there is no mandate that the applicant should provide details of clinical trials in patent specification, however I feel that the sufficiency of disclosure in accordance with section 10 particularly with regards to the utility of the product of the kind as mentioned in explanation appended to section 3(d) of the Patent (Amended) Act, 2005 has to be examined in strict sense because of the insertion of the said explanation. The reason for this may be that by allowing product claims the state is going to allow stronger rights. The criteria appears to be relaxed in respect of the process claims because of absence of such strict requirements in the explanation as appended to the section 3(d) of the Patent (Amended) Act, 2005. The documents relating to human clinical trials conducted by the applicant to substantiate the utility of the invention claimed by the applicant in EMR application fails to properly establish the utility of the claimed compound. Moreover, the said documents relating to substantiation of the utility was neither incorporated in the specification at the time of filing nor during prosecution of the instant application. Such amendments have to be carried out in prescribed manner in accordance with the Patent Rules. Thus, the applicant has not substantiated the utility of the compound in the complete specification by experimental proof such as clinical trials in the instant application. In view of my findings above and considering the submissions made by both the parties, their evidence, arguments at the hearing and all circumstances of this case, I hereby conclude that the claims relating to process i.e. 11 to 25 and 28 are allowable and claims 1 to 10, 26 and 27 of the instant application are not allowable as being obvious to a person skilled in the art i.e. do not involve an inventive step. Therefore, the claims do not constitute an invention u/s 2(1)(j) of the Patents (Amended) Act, 2005. The claims 1 to 10, 26 and 27 also fall u/s 3(d) of the Patents (Amended) Act,

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2005. The description of the invention in the complete specification is also insufficient with respect to the utility of the claimed compound. Therefore I hereby order to allow the application no. 85/DEL/1995 for the grant of patent with claims 11 to 25 and 28. The claims from 1 to 10, 26 and 27 i.e. the product claims pertaining to the compounds of formula I are rejected for the reasons mentioned above. The applicants are directed to submit the revised claims as per the directions given above within 30 days from the date of dispatch of this order. No orders for cost. Dated 22nd day of March 2007 (HARDEV KARAR) Asstt. Controller of Patents and Designs

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