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INTELLECTUAL PROPERTY PHILIPPINES

Pharmasia-Cuvest, Inc., } IPC No. 11-2007-00117 Petitioner, } Petition for Cancellation

} Patent No. 26419 -versus­ } Date issued: 15 July 2007

} Title: "Infusion solutions of Bayer Healthcare AG, } 1-cyclopropyl-6-fluoro-1,4-oxo-7

Respondent-patentee. } (t-plperazlnylj-qulnollne-S } carboxylic acid" }

x-------------------------------------------x Decision No. 200q - 01

DECISION

For decision is the Petition for Cancellation of Letters Patent No. 26419 entitled Infusion solutions of 1-cyclopropyl-6-flouro-1 ,4-dihydro-4-oxo-7-(1-piperazylin) quinoline-3-carboxylic acid granted on 15 July 1992 in the name of Robert Lamens, Hans Friedrich Mahler and Peter Serno and assigned to Bayer Aktiengesellschaft, (hereinafter referred to as respondent-patentee), filed by Pharmasia-Cuvest, Inc. with address at 3rd Floor Montepino Building, Amorsolo cor Gamboa sts. Legaspi Village, Makati City.

The ground for cancellation of the patent is that the molecule covered by said patent, ie. CIPROFLOXACIN is not novel at the time the application. Petitioner alleges:

"In support of this petition, it is respectfully pointed out that Patent No. 26419 (the subject of this petition) recites certain aqueous infusion solutions to address the instability of ciprofloxacin comprising of:

a) Ciprofloxacin; and a b) Physiologically tolerated acid.

This patent was granted on the basis of Application No. 34403 in the name of Robert Lamens and Peter Serno. The said infusion solution was invented to address the problem of instability of ciprofloxacin.

In order to fully understand these grounds for cancellation, Section 9 of R.A. 165 is hereto reproduced as follows:

SEC. 9. Invention not considered new or patentable. ; yAn invention shall not be considered new or capable of being! Vr\

Republic of the Philippines INTELLECfUAL PROPERTY OFFICE

'l~ I ~ nil PIIV"t Avp, Mlllclltl ritv 1')00 Philirmines • www inonhil l>OV nh

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patented if it was known or used by others in the Philippines before the invention thereof by the inventor named in an application for patent for the invention XXX if it is the subject matter of a validly issued patent in the Philippines granted on an application filed before the filing of the application for patent therefor.

With the cited provisions of R.A. 165, the law existing and enforced when this Application No. 34403 was filed and when the corresponding Philippine Patent No. 26419 was issued, it is very apparent that this patent is not novel on the grounds that:

a) The subject matter thereof is the same as that recited in Patent No. 24099 whose application No. 31216 was filed earlier that Application No. 34403 of the patent subject matter of this cancellation (A copy thereof is hereto attached as EXHIBIT "B" for easy reference.)

b) It was known or used by Klaus Grohe, by filing an earlier application for a patent in his name in the Philippines covering the same subject matter of the patent herein assailed. On the other hand, Mr. Grohe is a person not named as the inventor of the patent herein assailed.

A reading of Philippine Patent No. 24099 reveals that the subject matter thereof is practically identical to the subject matter of Philippine Patent No. 26419, namely: the subject of this petition recites certain infusion solutions to address the instability of ciprofloxacin comprising of the same functional ingredients, namely ciprofloxacin and a tolerated acid particularly lactic acid. Aside from the discussions in the specifications, particular examples of this combination were described as Examples 3, 7 and 8 in Patent No. 26419 of page 10 thereof.

Consequently, the filing of an earlier application which matured into Philippine Patent No. 24099 for the same subject renders Philippine Patent No. 26419 not novel and/or lacking in inventiveness and therefore not patentable."

. In support of its Petition for Cancellation, petitioner submitted the following fj evidence: / I(Y)

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EXHIBIT DESCRIPTION

"An Affidavit of Jorge Cesar San Diego

"Bn Copy of Letters Patent 26419

"0 " Resume of Cesar San Diego

"G" Copy of Letters Patent 24099

In its Answer, respondent-registrant raised the following special and affirmative defenses, to wit:

"7. Respondent repleads all the foregoing allegations.

"8. The petitioner is guilty of laches.

"9. The petition is already barred. Under Section 28 of Republic Act No. 165, a maximum period of three (3) years from the date of publication of the issuance of the patent in the Official Gazette is fixed within which a petition for the cancellation of a patent or any claim thereof must be filed. Section 28 of Republic Act No. 165 provides:

SEC. 28 General grounds for cancellation. - Any person may on payment of the required fee, petition the Director within three (3) years from the date of publication of the issue of the patent in the Official Gazette, to cancel the patent or any claim thereof, on any of the following grounds:

(a) That the invention is not new or patentable in accordance with sections seven, eight and nine, or that the design or utility model is not new or patentable under section fifty-five.hereof;

"10. Petitioner does not have standing to file the petition. Beyond the period of three (3) years provided in Section 28, only the Solicitor General may file the petition for the cancellation of the patent. Section 29 of Republic Act No. 165 provides:

SEC. 29. When patent may be cancelled at any time. - A petition to cancel a patent on any of the grOUnd~

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specified in the next preceding section may be filed any time by the Solicitor General

"11. Petitioner's allegation that the ciprofloxacin molecule is no longer novel is misplaced and deserves scant consideration. While ciprofloxacin may be known in the art, a subsequent composition claim or claims containing ciprofloxacin in combination with other elements based on a distinct and different inventive concept can qualify as novel and inventive as well.

11 .1 Having passed merit examination, the composition claims of Patent No. 24619 enjoy a presumption of novelty. The burden of proving otherwise is upon the petitioner.

11.2 Petitioner has not presented a clear demonstration in its petition why the composition claims in Patent No. 26419 (apart from the cirpofloxacin molecule alone) should be considered as no longer novel. All that the petitioner has demonstrated is that the claims contain ciprofloxacin. Composition claims, however, are not rendered non­novel simple because of the presence of a known molecule such as cirpofloxacin.

"12. The disclosure in Patent No. 24099 does not unequivocally teach all the elements of the claims of Patent No. 26419. While Patent No. 24099 addresses the problem of instability, page 14 of the disclosure in Patent No. 26419 makes clear that the problem addresses in the second patent is, among others, that of toxicity. Neither is there any equivalence in term of scope, inventive concept or teaching between the claims or claimed invention of Patent No. 26419 and those of 24099.

12.1 Petitioner's sole witness analyzes in his affidavit only one independent claim, namely, Claim 1 of Patent No. 26419 whereas said patent has a total of 18 claims. The petition and the supporting affidavit therefore failed to provide a comparative analysis of each dependent claim vis-a-vis the disclosure in Patent No. 24099. No basis is given whatsoever f~r the claimed invalidity of claims 2 to 18 of Patent No. ~,A

26419. ~1"

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12.2 It is a well-settled rule that each claim of a patent is presumed valid independently of the validity of other claims. [Jones vs. hardy, 727 F.2d 1524, 220 USPQ 1021 (Fed. Cir. 1984); Vanderberg vs. Dairy Equip. Co., 740 F. 2d 1560, 224 USPQ 195 (Fed. Cir.1984); Shellcore Inc., vs. Durham Indus., Inc., 745 F.2d, 621, 223 USPQ 584 (Fed. Cir. 1984); Loctite Corp. vs. Ultraseal Ltd., 781 F.2d 861, 228 USPQ 90 (Fed. Cir. 1985)] It is therefore a legal error to make a sweeping conclusion that all dependent claims are void simply because the independent claim to which they refer back is alleged to be invalid. The burden is clearly upon the petitioner to establish the invalidity of each and every claim if petitioner asserts the invalidity of the patent.

12.3 In Shellcor, Inc., VS. Durham Indus., Inc., 745 F.2d 621, 223 USPQ 584 (Fed. Cir. 1984), it was held that where the challenger wishes to show that a dependent claim is invalid, he must submit evidence directed to that claim. This is but logical considering that a dependent claim contains other elements in addition to the basic elements of the independent claim.

"13. Patent No. 26419 is valid and covers a patentably distinct selection invention of the more generic invention set forth in Patent No. 24099. Patent No. 24099 recites a generic claim wherein ciprofloxacin is identified as one of the species compound. Amounts of ciprofloxacin per unit solution are not claimed in 24099 but are claimed in 26419. The claims directed to amounts and concentrations in Patent No. 26419 (which are not present in 24099) are not bereft of significance. The selection claims in Patent No. 26419 are novel and inventive and are purposive in that they are intended to attain delicate low toxicity levels while retaining effectivity against a broad spectrum of bacterial infection, apart from improving the stability of the solution. The Patent No. 26419 as species is patentably distinct from Patent No. 24099 is supported by ruling to the effect that genera do not anticipate species. [Corning Glass Works vs. Sumitomo Elec. USA, Inc., 868 F.2d 1251, USPQ 2d 1962 (Fed Cir. 1989)].

"14. The validity of Respondent's patent corresponding t~ J./t().. Patent No. 26419 has been affirmed in other jUrisdictionsl'!;fY 0

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Canadian patent Nos. 1,228,547 and 1,282,006 correspond, respectively, to Philippine Patent Nos. 24099 and 26419. In a Decision of Canadian Federal Court in the case of Bayer A.G. vs. Novopharma Ltd., the Canadian Federal Court confirmed the validity of Canadian Patent No. 1,282,006 (corresponding to Philippine Patent No. 26419) over Canadian Patent No. 1,228,547 (corresponding to Philippine Patent No, 24099). In upholding the validity and patentability of the claims of the second patent, the Canadian Federal Court held:

'The problems caused by the '547 patent were not known outside Bayer. It took a team of experts two years to develop the solution to the intolerance problem embodied in the '006 patent. In arriving at the solution, Bayer did not merely dilute one substance but had to find the correct balance between the active compound and other elements of the drug; and exercise for which there were a myriad of permutations and combinations."

Attached as Annex "A" hereof is a copy of the decision rendered by the Canadian Federal Court. Attached as Annexes "A-1" to "A-2" respectively are copies of Canadian Patent Nos. 1,228.547 and 1,282,006.

"15. Petitioner seeks relief in bad faith and does not come to court with clean hands. By its own admission in its petition, it has come to know of the existence of Respondent's patents through a patent search, and yet, without awaiting the final resolution of this Honorable Office regarding the validity of the said patents, and while yet one of said patents remains in force, it has already embarked on selling products covered by Respondent's patent. Evidently, Petitioner seeks relief from this Honorable Office under the patent law while its mocks and scoffs the very same patent law under which its seeks relief. Attached as Annex "B" is the Affidavit of witness Dr. Abola regarding Petitioner's infringement of the patent.

"16. Respondent further submits and makes part of this Answer as Annex "C" hereof the Affidavit (with annexes) of its expert witness.

In support of its position, respondent-registrant submitted the fOllowing~l evidence: f I !" I

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ANNEX DESCRIPTION

"AU Copy of document (Federal court judgment in Canada) between Bayer AG, Bayer Healthcare AG and Bayer, Inc. and Novopharm Limited and The Minister of Health dated March 24, 2006

US" Affidavit of Dr. Luis Abola

"C" Affidavit of Rosella L. Fernandez

A preliminary conference was set on 8 November 2007 but no amicable settlement was reached between the parties. The issues are whether the subject matter of the second patent, Patent No. 26419 is no longer novel or is obvious to a person skilled in the art and whether the petitioner has a standing to file the petition.

At the outset, respondent - registrant argues that the petition is already barred. It cites Sec. 28 of Republic Act 165, the law in force when the patent was granted.

The challenged Patent no. 26419 was granted under the old patent law, R.A. 165, hence, its rights shall be enforced citing the provisions of the old patent law, R.A. 165. Section 28 of Republic Act 165 provides for a period to file suit for cancellation of patented design, thus:

"Section 28. General grounds for cancellation. - Any person may on payment of the required fee petition the Director within three years from the date of publication of the issue of the patent in the Official Gazette, to cancel the patent or any claim thereof, on any of the following grounds:

(a) That the invention is not new or patentable in accordance with sections seven, eight and nine, or that the design or utility model is not new or patentable under section fifty-five thereof:xxx"

It is noted that more than three (3) years had lapsed from the publication of the issuance or grant of respondent-registrant's in 15 July 1992. However, this Bureau believes that the validity of the patent can still be questioned after three years from date of publication considering that it affect substantive rights. Respondent-patentee's claim that petitioner has no standing must be interpreted together with Section 236 of the neti law (Republic Act 8293) which states:

Section 236 provides:

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"Section 236. Preservation of Existing Rights. - Nothing herein shall adversely affect the rights on the enforcement of rights in patents, utility models, industrial designs, marks and works, acquired in good faith prior to the effective date of this Act."

No patent rights can be preserved if the invention is invalid for lack of novelty. It should be noted that there is a mere presumption of validity accorded by the issuance of a patent. But the presumption implies that its validity can be overcomed by substantial evidence.

Moreover, in the case of Bank of the Philippine Islands v. Court of Appeals GR No. 146923, April 30, 2003, the Supreme Court held that "Rules of procedure are used to help secure and not override substantial justice . Even the Rules of Court mandate a liberal construction in order to promote their objective of securing a just, speedy and inexpensive disposition of every action and proceeding. Since rules of procedure are mere tools designed to facilitate the attainment of justice, their strict and rigid application which would result in technicalities that tend to frustrate rather than promote substantial justice must always be avoided xxxx." Hence, we shall delve into the merits of the petition to determine the novelty and validity of the patent.

The subject matter of the challenged Patent No. 26419 as expressed in its abstract is as follows:

"An aqueous infusion solution containing 0.015 to 0.5g of 1-cyclopropyl-6-flouro­1,4-dihydro-4-oxo-7-(1-piperazylin) quinoline-3-carboxylic acid per 100 ml of aqueous solution and an amount of at least one physiologically tolerated acid which suffices to dissolve the active compound."

The claims of the Patent No. 26419 (Exhibit "B") are as follows:

WHAT 15 CLAIM 15:

"1. An aqueous infusion solution containing 0.015 to 0.5g of 1 ­cyclopropyl - 6 - flouro - 1, 4 - dihydro - 4 ­ oxo ­ 7 - (1-piperazinyl) - quinoline - 3 - carboxylic acid per 100 ml. Of aqueous solution and an amount of physiologically tolerated acid which suffices to dissolve the active compound.

"2. An infusion solution according to claim 1, containing a mixture of physiologically tolerated acids to dissolve the active compound.

"3. An infusion solution according to claim 1, wherein the acid is member selected from the group consisting of hydrochloric acid, methanesulphonic acid, propionic acid, succini acid, glutaric acid, citric acid, fumaric acid, maleic acid, tartaric acid, glutamic aCid'/(;1

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gluconic acid, glucoronic acid, galacturonic acid, ascorbic acid, phosphoric acid, nitric acid, acetic acid, malic acid, L-aspartic acid and lactic acid.

"4. An infusion solution according to claim 1, wherein the acid is selected from the group consisting of lactic acid, hydrochloric acid and mixtures of lactic acid.

"5. An infusion solution according to claim 1, containing up to 5 moles per mol of active compound, of the physiologically tolerated acids.

"6. An infusion solution according to claim 1, containing 0.9 to 5 mols per mol of active compound of the physiologically tolerated acids.

"7. An infusion solution according to claim 1, containing 1.04 to 2.2 mols per mol of active compound of the physiologically tolerated acids.

"8. An infusion solution according to claim 1, containing up to 5 mols per mol of active compound of lactic acid.

"9 . An infusion solution to claim 1, containing 0.99 to 1.50 mols of lactic acid per mol of active compound .

"10. An infusion solution according to claim 1, containing 1.12 to 1.24 mols of lactic acid per mol of active compound.

"11. An infusion solution according to claim 1, containing 0.9 to 5 mols per mol of active compound of lactic acid plus another physiologically tolerated acid.

"12. An infusion solution according to claim 1, having a pH from 3 to 5.2.

"13. An infusion solution according to claim, having a pH from 3.6 to 4.7.

"14. An infusion solution according to claim 1, having a pH from 3.9 to 4.5.

"15. An infusion solution according to claim 1, having a pH from 4.1 to 4.3.

"16. An infusion solution according to claim 1, which is isotonic.

"17. An infusion solution according to claim 1, containing 0.99 to 1.5 mols of lactic acid and 0.0 to 0.80 mol of hydrochloric acid per m"7[~

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of active compound and relative to 100 ml of solution, 0.6 to 2.2 g of NaCI.

"18. An infusion solution according to claim 1, containing 1.04 to 1.4 mols of lactic acid and 0.0 to 0.80 mol of hydrochloric acid per mol of active compound and relative to 100 ml of solution, 0.75 to 1.2 g of NaCI."

The compound ciprofloxacin is the molecular structure described in Claim 1 as 1­cyclopropyl-6-flouro-1, 4-dihydro-4-oxo-7(1-piperazinyl)-quinoline-3-carboxylic acid. The generic name was mentioned in line 2 page 3 of patent 26419.

The reason for using tolerated acid is actually to dissolve the active compound and to stabilize the solution (starting from the last par. of page 3 of said patent). On the 2nd paragraph of page 4 of patent 26419, lactic acid as tolerated acid is particularly preferred although other acids were named therein.

On the other hand, Patent 24099 is entitled "solutions of lactic acid salts of piperazinylquinolone and piperazinylazaquinolone-carboxylic acids" which was issued in 5 March 1990 based on an application filed in 17 September 1984.

As can be seen from the claims of Patent No. 24099, claim no. (3) states:

" A solution according to claim 1, which contains the lactate of 1 -cyclopropyl - 6 - flouro - 1, 4 - dihydro - 4 - oxo - 7 - (1-piperazinyl) - quinoline - 3 - carboxylic acid as the lactic salt thereof." (Exhibit "C")

The subject matter of Patent No. 24099 is also an infusion solution (Claim 1, the 1st abstract, par. page3). The active ingredient among others is ciprofloxacin (the

molecular structure of which is described as compound A in line 8, page 4 meaning 1­cyclopropyl-6-f1ouro-1 ,4-dihydro-4-oxo-7-(1-piperazinyl)-quinoline-3-carboxylic acid-the same molecular structure in patent no. 26419. Both are aqueous solutions (claim 1) and it uses acid preferably lactic acid which does not lead to precipitates.

The active compound of ciprofloxacin (the generic name given) of challenged Patent No. 26419 is identical to the active compound of claim 3 of earlier issued patent no. 24099. What remains to be determined is whether the infusion solution of 0.015 to 0.5g of the active compound is contained in a 100ml aqueous solution, which combines with an acid that dissolves the compound.

It is to be understood that paragraphs 15 to 20 on page 9 of Patent 24099 refer to formulations. It reads "The solutions according to the invention are prepared by dissolving the active substance or the lactic acid salt thereof and if appropriate customary auxiliaries, in a solution of lactic acid or mixture of lactic acid and, for example. sodium lactate. if necessary with slight warming. If appropriate. water o;JIY mixture of water and sodium hydroxide solution is also added to adjust the desire~

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concentrated of the active substance and/or the ph of the solution". The use of lactic acid is also embodied in the challenged invention as described in pages 3 and 3 of the Patent No. 26419 and particularly claims under paragraphs 2, 3 and 4.

Respondent-patentee argues that the 0.015 to .5g. of the active compound per 100 ml of aqueous solution embodied in Patent No. 26419 address toxicity levels. (Affidavit of Rosella Fernandez - Exhibit "C"). Yet, the ranges of the ratio of weight enumerated in the earlier patent are close to the claimed weight of 0.015 to 0.5g of the challenged patent. No remarkable difference has been except that the infusion solutions have low toxicity level. (page 14 of Patent 26419)

This specific formulation of Patent No. 26419 is non-inventive because it is within the knowledge of a person skilled in the art and also anticipated by its embodiment in an earlier filed application 31216 upon which Patent No. 24099 was granted. As stated in both patents, the intention of both patents is to make infusion solutions that will dissolve the active ingredient abstract of Patent No. 24099. Logic dictates that if you have an X weight of active ingredient that can be dissolved in 100 ml water, surely, it is easier to dissolve the same X amount of ingredient in 1000 ml water. That is precisely what Patent 26419 did.

As explained by the petitioner's witness in his affidavit (Affidavit of Jorge Cesar San Diego- Exhibit "A"), Patent No. 24099 provides certain examples of the infusion formulation, where compound A represents ciprofloxacin, namely:

Example 3 (page 10 of Exhibit "C")

Compound A 10 gm Lactic acid (90% by weight) 4.85 gm Water 1000 ml

Example 7

Compound A 300gm Lactic acid (90% by weight) 177.3 gm Water 1000 ml

Example 8

Compound A 200 gm Lactic acid (90% by weight) 75 gm Water 2000 ml

Thus by ratio and proportion ­

Example 3 has 10 grams ciprofloxacin to one liter of water Example 7 has 50 grams ciprofloxacin to one liter of wat1~

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Example 10 has 100 grams ciprofloxacin to one liter of water

On the other hand, Claim 1 of Patent No. 26419 has only 0.15 to 5 grams of ciprofloxacin to one liter of water which has been diluted almost ten times in Example 10 to two times in Example 3. The use of acids particularly lactic acids is termed in claim 1 of 26419 as to dissolve the active ingredient. In Patent No. 24099 it is called "which does not lead to precipitates"

The author, Trevor Cook in his book , A User's Guide to Patents (2002) p. 279.: explained "Claims to mixtures having no more than the additive utility of the components of the mixture are unlikely to be inventive unless at least one component does not form part of the state of the art. However, invention may lie in making a selection of components which provide an over-all effect greater than merely additive, although such 'synergy' should be disclosed in the patent, and can be hard to show, as in Richardson-Vicks Patent, where a patent to a mixture was held obvious. (1995) RPC 568; (1997) RPC 888, CA."

Respondent-registrant also cites the decision of the Canadian court submitted in the Answer. It is alleged that in a decision of a Federal Court in Canada, Patent NO.1 282 006 was held valid despite the existence of Canadian Patent No. 1222 547. In submitting this decision, Bayer contends that Philippine Patent No. 24099 is identical to Canadian Patent No.1 222 547 while Philippine Patent No. 26419 is identical to Canadian Patent NO.1 282 006.

For Philippine courts to apply the Canadian decision on the matter, it should first be considered whether or not the alleged patents involved are the same. The Bureau perceives that the patents are not the same. There is no question that Canadian Patent No. 1 282 006 (ANNEX "5" hereof) has 37 claims while the alleged corresponding Philippine Patent No. 26419 has only 18 claims.

Moreover, in par. [83] of the Canadian decision, the validity of Canadian Patent No. 1 282 006 was sustained because of its low toxicity and specifically claimed in Claim 36 of an infusion solution for the therapeutic use of human or animal body. Yet, the alleged corresponding Philippine Patent 26419 has only 18 claims and therefore has no Claim 36.

Considering that Application for Patent No. 24099 was filed before the application of Patent No. 26419, the latter should not be considered novel according to Section 9 of R.A. 165 which reads: an invention is not novel if it is the subject matter of a validly issued patent in the Philippines granted on an application filed before the filing of the application for a patent therefor.

WHEREFORE, premises considered the instant PETITION FOR CANCELLATION is hereby GRANTED. Accordingly, Letters Patent No. 26419 entitled Infusion solutions of 1-cyclopropyl-6-flouro-1 A-dihydro-4-oxo-7-(1-piperazylin) quinollne-Svcarboxylic acid granted on 15 July 1992 in the name of Robert Lame~

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Hans Friedrich Mahler and Peter Serno and assigned to Bayer Aktiengesellschaft, (hereinafter referred to as respondent-registrant), filed by Pharmasia-Cuvest, Inc.1­1996-52993 dated 5 May 2005, is as it is hereby CANCELLED.

Let a copy of this decision be forwarded to the Bureau of Patents for appropriate action in accordance with this Decision.

SO ORDERED.

Makati City, 25 January 2009 .

ES LUTA BELTRAN-ABELARDO D' ector, Bureau of Legal Affairs A

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