8-K

UNITED STATES
SECURITIES AND EXCHANGE COMMISSION

WASHINGTON, D.C. 20549

FORM 8-K

CURRENT REPORT
PURSUANT TO SECTION 13 OR 15 (d) OF
THE SECURITIES EXCHANGE ACT OF 1934

Date of Report (Date of earliest event reported): April 2, 2004

MYLAN LABORATORIES INC.

(Exact name of registrant as specified in its charter)

Pennsylvania
(State or other jurisdiction
of incorporation Number) 1-9114
(Commission File
Number) 25-1211621
(I.R.S. Employer
Identification No.)

1500 Corporate Drive
Canonsburg, PA 15317
(Address of principal executive offices)

(724) 514-1800
(Registrant’s telephone number, including area code)

Item 5. Other Events and Regulation FD Disclosure.

     On April 2, 2004, correspondence was submitted to the FDA on behalf of Mylan Laboratories Inc. (the “Company”), with regard to the Company’s generic transdermal fentanyl product, in response to correspondence submitted on behalf of Alza Corporation. Copies of such correspondence are attached hereto as Exhibits 99.1 and 99.2.

Item 7. Financial Statements and Exhibits.

(c) Exhibits.

Exhibit No.	Description
99.1	Letter to the FDA submitted on behalf of the Company, dated April 2, 2004.
99.2	Letter to the FDA submitted on behalf of the Alza Corporation, dated March 31, 2004.

SIGNATURE

     Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

Date: April 2, 2004	MYLAN LABORATORIES INC.
	By:	/s/ Robert J. Coury
		Robert J. Coury
		Vice Chairman and Chief Executive Officer

EXHIBIT INDEX

Exhibit No.	Description
99.1	Letter to the FDA submitted on behalf of the Company, dated April 2, 2004.
99.2	Letter to the FDA submitted on behalf of the Alza Corporation, dated March 31, 2004.

  EX-99.1 3 j0675101exv99w1.txt LETTER TO THE FDA DATED APRIL 2, 2004 Exhibit 99.1 LAW OFFICES ROTHWELL, FIGG, ERNST & MANBECK A PROFESSIONAL CORPORATION G. FRANKLIN ROTHWELL 1425 K STREET, N.W. MARTHA CASSIDY, Ph.D. E. ANTHONY FIGG SUITE 800 ROBERT H. CAMERON BARBARA G. ERNST WASHINGTON, D.C. 20005 THOMAS E. McKIERNAN HARRY F. MANBECK, JR. MICHAEL J. MORAN, Ph.D. GEORGE R. REPPER TELEPHONE (202) 783-6040 ANNE M. STERBA STEVEN LIEBERMAN FACSIMILE (202) 783-6031 LISA N. PHILLIPS* VINCENT M. DeLUCA www.rothwellfigg.com LEIGH Z. CALLANDER JOSEPH A. HYNDS C. NICHOLE GIFFORD ELIZABETH A. LEFF REGINA A. BAILEY RICHARD WYDEVEN April 2, 2004 MONICA S. DAVIS* MARTIN M. ZOLTICK PATRICK T. SKACEL MINAKSI BHATT VIA FACSIMILE AND HAND DELIVERY BRIAN S. ROSENBLOOM MICHAEL G. SULLIVAN TARA J. PATE SHARON L. DAVIS MONICA C. KITTS ROBERT B. MURRAY BRIAN A. TOLLEFSON* CARLA C. CALCAGNO JOYCE H. A. VON NATZMER JEFFREY L. IHNEN JOO MEE KIM* GLENN E. KARTA CHRISTOPHER M. DURKEE STEVEN M. GIOVANNETTI* OF COUNSEL *NOT ADMITTED IN D.C. STEPHEN B. PARKER JOHN A. McCAHILL BARBARA WEBB WALKER Gary J. Buehler Director, Office of Generic Drugs Center for Drug Evaluation and Research Food and Drug Administration MPN II, HFD-600 7500 Standish Place Rockville, MD 20855 Daniel E. Troy, Esq. Chief Counsel Food and Drug Administration 5600 Fishers Lane, GCF-1 Rockville, MD 20857 RE: MYLAN TECHNOLOGIES INC. ANDA NO. 76-258 Dear Messrs. Buehler and Troy: On March 26, 2004, we wrote on behalf of Mylan Technologies Inc. ("Mylan") to explain why pediatric exclusivity does not apply to Mylan's already-approved ANDA. Alza Corporation ("Alza") is not entitled to the regulatory exclusivities of the Hatch-Waxman amendments, because it did not sue Mylan within the 45-day statutory period after receiving Mylan's notice of a Paragraph IV certification. Contrary to Alza' argument, so-called pediatric exclusivity is not a patent term extension. Instead, this exclusivity is in the form of a stay of regulatory approval that Congress grafted into the regulatory stays already embodied in Hatch-Waxman. Entitlement to pediatric exclusivity is statutorily predicated on compliance with the 45-day deadline for initiating patent infringement litigation. This result is clear under the statute because: - Mylan submitted an ANDA containing a Paragraph IV certification to Alza's Orange-Book-listed patent number 4,588,580 (the "580 Patent") and properly served Alza with notice of that certification pursuant to 21 U.S.C. Section 355(j)(2)(A)(vii)(IV). Mr. Gary Buehler ROTHWELL, FIGG, ERNST & MANBECK Daniel E. Troy, Esq. April 2, 2004 Page 2 - Because Alza did not sue Mylan within 45 days (a fact confirmed by the FDA in the letter attached to Mylan's March 26, 2004 letter), Alza lost the benefit of any otherwise applicable Hatch-Waxman exclusivities and Mylan's ANDA became approvable effective "immediately." 21 U.S.C. Section 355(j)(5)(B). - FDA was cognizant of this fact and issued a final approval of Mylan's ANDA, not a tentative approval, on November 21, 2003. - The Hatch-Waxman provision governing application of so-called "pediatric exclusivity" in cases in which a Paragraph IV certification has been submitted is 21 U.S.C. Section 355a(c)(2)(B), and no other. This provision expressly defines pediatric exclusivity as an extension of "the period during which an application may not be approved under section 505(c)(3) or section 505(j)(5)(B)," the latter of which applies to ANDAs, like Mylan's, containing Paragraph IV certifications. This provision does not extend the patent expiration date. - In the case of ANDAs containing Paragraph IV certifications, section 355(j)(5)(B) defines "the period during which an application may not be approved" as the 30-month period commencing with receipt of the applicant's notice or until a court decision finding the patent valid and infringed. (Referred to herein for convenience as the 30-month period.) As the FDA has already recognized by its granting final approval to Mylan, no such period ever existed in this case. Thus, there is no period that can be "extended" through pediatric exclusivity. - Although Alza asked the district court in post-trial briefs to apply its pediatric exclusivity to Mylan, the district court's March 25, 2004 order merely delays the effective date of Mylan's final approval until the '580 patent expires on July 23, 2004. - The district court's order did not create a period during which Mylan's application may not be approved "under section 505(c)(3) or section 505(j)(5)(B)." Instead, it merely put into effect a delay of Mylan's final approval under 35 U.S.C. Section 271(e)(4)(A). On March 31, 2004, Alza's counsel submitted a letter asserting, in summary, that: (i) Mylan's final approval must be revoked and FDA must "deem" the final approval to be a "tentative approval"; (ii) Mylan must then be compelled to change its Paragraph IV certification to a Paragraph III or Paragraph II certification, because Mylan's Paragraph IV certification ostensibly is no longer accurate; and (iii) Alza should be rewarded with an additional six months of post-patent Hatch-Waxman pediatric exclusivity as to Mylan (even though Alza abandoned all 2 Mr. Gary Buehler ROTHWELL, FIGG, ERNST & MANBECK Daniel E. Troy, Esq. April 2, 2004 Page 3 Hatch-Waxman exclusivities by failing to sue within 45 days) because to enforce the statute as written would "frustrate Congressional policy." Alza is wrong. (1) THERE IS NO REASON FOR FDA TO REVOKE MYLAN'S FINAL APPROVAL. The FDA has granted final approval of Mylan's ANDA. The district court's order did not and could not revoke Mylan's final approval. It did nothing more than delay the effective date of that approval to the expiration date of Alza's patent, pursuant to 35 U.S.C. Section 271(e)(4)(A). Mylan, will, of course, comply with the court's order until its injunctive effect ends upon patent expiration, unless it is overturned earlier on appeal. Alza's statement at page 6 of its letter that "the district court's Order compels FDA to change the existing approval" has no basis. The district court, adopting the language of the statute, merely ordered that "the effective date of any approval of Mylan's ANDA product shall be no earlier than the date of the expiration of the '580 patent family [July 23, 2004]." The order does not direct FDA - not a party to the litigation - to do anything, and there is no need for FDA to do anything to give effect to the district court's order. The order is directed to Mylan and mandates when Mylan's approval shall become effective. Alza further argues that the effective date of Mylan's ANDA approval "must be reset." But it already has been reset by the district court to the date of patent expiration, July 23, 2004. The legislative history cited by Alza in page 4 of its letter (H.R. Rep. No. 98-857, pt. 1, at 46 (1984)) actually undercuts Alza's assertions. It does not reflect an intention by Congress that FDA needs to reset the effective date of an approval in a case such as this. Instead, it says that if commercial marketing has not begun the court's order would change the effective date of the approval. Alza's reliance on the Teva, Mylan and Barr situations to support its contention that Mylan's finally approved ANDA must be converted to a tentative approval also is without merit. First, the Teva, Mylan and Barr cases are all easily distinguishable. Unlike the present case, in each of those cases the ANDA applicants were sued within 45 days. Each of those applicants voluntarily submitted Paragraph III certifications after an adverse decision was entered by a district court. Moreover, Barr settled its lawsuit with a final and binding stipulation that the patent in suit was valid and infringed. None of those circumstances exist here. Second, contrary to Alza's assertion, none of the Teva, Mylan and Barr situations recognize or constitute any FDA authority to convert Mylan's final approval to a tentative approval. In the letter sent to Mylan, the FDA expressly stated that it was Mylan's voluntary submission of the Paragraph III certification that enabled FDA to convert Mylan's ANDA approval to a tentative approval. (See Ex. G to Alza's 3/31/04 letter). Likewise, in the letter sent to Teva, the FDA expressly stated that the conversion of final approval to a tentative approval was based on both the court order and the applicant's change in certification. (See Ex. F to Alza's 3/31/04 letter). Thus, it was the applicant's decisions voluntarily to change their 3 Mr. Gary Buehler Daniel E. Troy, Esq. ROTHWELL, FIGG, ERNST & MANBECK April 2, 2004 Page 4 certifications to Paragraph III certifications (and, in the case of Barr, to settle litigation with a final and binding stipulation of validity and infringement) that caused the change in the status of approval to a tentative approval, and not the fact that the ANDAs had delayed effective approval dates, as Alza contends. Here, Mylan was not sued within 45 days. Under the applicable regulation, 21 C.F.R. section 314.94(a)(12)(viii)(A), Mylan is not required to change its patent certification --a certification that is still factually accurate in view of Mylan's intention to seek appellate review of the district court decision. Adopting Alza's theory that ANDA applicants must change their certification to a Paragraph III certification when they receive an adverse decision in the district court would eviscerate the ANDA applicants' appeal rights. Under Alza's theory, Mylan's certification should now be deemed a Paragraph III certification and pediatric exclusivity applied through the end of six months after patent expiration under section 355a(c)(2)(A). Therefore, under Alza's theory, Mylan and similarly situated ANDA applicants who lose in the district court but then win on appeal would nonetheless still be subject to pediatric exclusivity as if they were originally Paragraph III filers. That would be an absurd result because if Mylan wins its appeal, Alza cannot be entitled to pediatric exclusivity based on an invalid or noninfringed patent. Alza does not provide a single example in its 11 page letter of any instance in which FDA has converted a finally approved ANDA to tentative approval over the objection of an applicant based on a district court opinion and before the appeal process has been exhausted. Moreover, even if a change of Mylan's approval to a tentative approval were appropriate, which it clearly is not, that change would not alter the fact that Alza's pediatric exclusivity does not apply to Mylan. Pediatric exclusivity is governed by section 355a(c)(2)(B), the applicability of which has nothing to do with the status of the approval. Alza also says at page 5 that there are "important policy reasons" to revoke Mylan's final approval because doing so would enable FDA to ensure that Mylan "continues to satisfy all applicable criteria when outstanding barriers to approval are finally removed." That argument is circular. There are no "outstanding barriers to approval" unless the approval is revoked. Further, FDA always has the authority to police Mylan's compliance with relevant statutory and regulatory criteria for maintaining its approval, and FDA does not need to revoke Mylan's approval in order to determine whether Mylan is compliant. In short, there is no need for FDA to do anything to give effect to the court's order, much less take the extraordinary step of revoking a final approval, and Alza has not supplied any precedent for FDA to take such action. (2) MYLAN CANNOT BE REQUIRED TO CONVERT ITS PARAGRAPH IV CERTIFICATION. Alza writes at page 7 of its letter that "Mylan's Paragraph IV certification should be converted to a Paragraph III certification." Later in the same paragraph, Alza asks FDA to 4 Mr. Gary Buehler Daniel E. Troy, Esq. April 2, 2004 Page 5 ROTHWELL, FIGG, ERNST & MANBECK "correct" Mylan's certification to a Paragraph III certification. That would be contrary to law. "[T]here is no statutory provision which grants to the FDA, either expressly or implicitly, the authority to change a 'IV certification' to a 'III certification.'" Mylan v. Thompson, 207 F.Supp.2d 476, 487 (N.D. W.Va.2001). Alza acknowledges that FDA's regulation concerning conversion from a Paragraph IV certification to a Paragraph III certification, 21 C.F.R. Section 314.94(a)(12)(viii)(A), is expressly limited to situations in which the NDA holder has filed suit within 45 days and so does not apply here. Nor is Mylan's Paragraph IV certification inaccurate. The statute requires Mylan to certify as to its opinion with respect to the listed patent. Mylan's good faith belief that the '580 patent is invalid, unenforceable and not infringed has not changed as a result of the district court's decision. Mylan will appeal that decision, on grounds that it was based on clear errors of law and fact. As stated above, Mylan's right to appeal is very important. If Mylan wins, Alza cannot be entitled to pediatric exclusivity based on an invalid or noninfringed patent. Contrary to Alza's argument, the FDA does not require a change in the patent certification when a district court has entered a finding of infringement and validity. For example, Barr was not required to convert its Paragraph IV certification to a Paragraph III certification upon receipt of an unfavorable district court decision in its litigation with Eli Lilly involving fluoxetine (Prozac(R)). See attached FDA letter. Barr maintained its Paragraph IV certification and ultimately prevailed on appeal. The agency has recognized that to require such a change would inappropriately cause the first Paragraph IV filer to lose its 180-day exclusivity with respect to other ANDA applicants. (3) ALZA ABANDONED ANY RIGHT TO PEDIATRIC EXCLUSIVITY AS TO MYLAN. As discussed in our March 26 letter, pediatric exclusivity is not a patent term extension, it is a type of Hatch-Waxman market exclusivity that is applicable only in narrow circumstances defined by statute. One fundamental trade-off under Hatch-Waxman is that an NDA holder must sue within the statutory 45-day period in order to avail itself of Hatch-Waxman exclusivities. Alza did not do so and thereby abandoned any claim to pediatric exclusivity as to Mylan's ANDA. Alza protests at page 6 of its letter that it is entitled to pediatric exclusivity because of the district court's ruling and because of the "intent" underlying Congress's "promise" of pediatric exclusivity. Of course, Congress expresses its "intent" and makes "promises" in only one way: by enacting a statute. Where is the language of a statute is clear, it is plain error for an agency to depart from that statutory language in order to give effect to what someone thinks Congress meant to say or should have or could have said. Chevron U.S.A., Inc. v. Natural Resources Defense Council, Inc., 467 U.S. 837, 81 L. Ed. 2d 694, 104 S. Ct. 2778 (1984). That is exactly what Alza is asking FDA to do. 5 ROTHWELL, FIGG, ERNST & MANBECK Mr. Gary Buehler Daniel E. Troy, Esq. April 2, 2004 Page 6 The text of section 355a(c)(2)(B) clearly provides that, when, as here, a Paragraph IV certification has been submitted and a court has found the patent to be valid and infringed, pediatric exclusivity is available only as a post-patent expiration extension of "the period during which an application may not be approved under section 505(c)(3) or section 505(j)(5)(B)." 21 U.S.C. Section 355a(c)(2)(B). Because Alza failed to initiate suit within the statutory 45-day period, there never was such "a period" during which the application could not be approved, so there is no period to extend. Alza contends that "[s]ix months exclusivity results directly from Mylan's existing Paragraph IV certification" because, according to Alza, section 355a(c)(2)(B) requires only a Paragraph IV certification and a finding of infringement. (Alza's letter at 6). Alza, however, ignored the statutory language defining pediatric exclusivity as an extension of the period during which the application could not be approved under section 355(j)(5)(B). Alza also conveniently leaves out of its analysis that there never was such a period because it did not sue within 45 days. Alza's discussion of the provisions of section 355(j)(5)(B) that relate to certifications under Paragraphs II and III is inapposite. There is no dispute that the certification that Mylan provided was properly under Paragraph IV. The period during which an application containing a Paragraph IV certification may not be approved under section 355(j)(5)(B) is the 30-month period - which never existed in this case. Alza finally addresses its failure to meet the 45-day deadline in footnote 4 on page 7 of its letter. It argues that section 355(c)(2)(B) "does not refer to the 30 month stay." This argument is wrong and ignores the language of the statute. The statute explicitly defines pediatric exclusivity as a post-patent extension of "the period during which an application may not be approved under... section 505(j)(5)(B)," which is the 30-month stay provision. Because that period did not exist here, Mylan's application was eligible for immediate final approval, which was granted on November 21, 2003. Alza also argues that it is entitled to pediatric exclusivity under sections dealing with Paragraph II and III certifications because Mylan's ANDA ostensibly should be corrected or deemed to include a Paragraph II or III certification. As discussed in part (2) above, there is no lawful basis to require Mylan to change its Paragraph IV certification. Moreover, a Paragraph IV certification "has been submitted," so section 355(c)(2)(B) expressly applies. (4) THIS CASE IS VERY DIFFERENT FROM RANBAXY. Alza improperly relies on the district court's decision in Ranbaxy Labs Ltd. v. FDA. Ranbaxy was a case about pediatric exclusivity, but any similarity ends there. In Ranbaxy, suit was filed by the NDA holder within 45 days. There was a 30-month stay in effect and, thus, there was a period during which Ranbaxy's application could not be approved under section 355(j)(5)(B). In Ranbaxy, the application had never been finally approved; only a tentative approval had been granted and Ranbaxy was taking the position that 6 Mr. Gary Buehler Daniel E. Troy, Esq. April 2, 2004 Page 7 Rothwell, Figg, Ernst & Manbeck FDA is required, as a matter of course, to issue a final approval immediately upon patent expiration without regard for FDA's continuing discretion to review the application. There are no such considerations here. Further, there never was a court decision finding the patent valid and infringed; the case had been dismissed as moot upon expiration of the patent in suit. For all of those reasons, section 355a(c)(2)(B) was not even at issue in Ranbaxy. (5) ADOPTING ALZA'S POSITION WOULD RENDER THE 45-DAY PERIOD MEANINGLESS. The public's interest in accelerating the availability of generic drugs to American consumers sits at Hatch-Waxman's core. The legislation balances that public interest against the intellectual property rights of NDA holders. The 45-day filing provision is central to this carefully-crafted Congressional compromise and balance, but Alza's position, if adopted, would render it essentially meaningless. Hatch-Waxman provides for periods of exclusivity to NDA holders that are separate and apart from whatever rights they may have under the patent laws. These non-patent exclusivities include the 30-month stay of approval under section 355(j)(5)(B) and six months of post-patent pediatric exclusivity under section 355a. As discussed above and in our March 26, 2004 letter, Hatch-Waxman's statutory quid pro quo for these exclusivities in a case where a Paragraph IV certification has been submitted is that the NDA holder/patentee must file suit within 45 days after receiving a notice letter. The statutory purpose behind that 45-day filing deadline is obvious. It encourages prompt suits so patent issues can be resolved quickly and so generic applicants will not face potentially catastrophic suits for damages which would otherwise be brought at a later time, such as after a final approval has been granted and the generic applicant is preparing for a market launch.(1) That strategy, if successful, could add years to the time it takes for the generic company to clear patent hurdles and bring a generic drug to market. If FDA adopts Alza's position that pediatric exclusivity may be applied to Mylan's ANDA notwithstanding Alza's failure to sue Mylan on time, the most powerful economic incentive for a branded pharmaceutical company to file suit within 45 days will be lost. The single 30-month stay of approval available under current law does not provide sufficient enticement for a prompt suit. Generics are already seeing branded companies choose not to file suit within 45 days for strategic reasons, then resisting declaratory judgment jurisdiction when generic applicants seek to join issue on the patents. Six months of extra, post-patent market exclusivity, on the other hand, provides a huge economic incentive to file suit promptly. That incentive will be gone if FDA agrees with Alza. In addition, adoption of Alza's position would result in every ANDA applicant with a Paragraph IV certification having to change its patent certification upon a district court decision finding the patent to be valid or infringed. This is completely contrary to statutory provisions - --------------------- (1) Alza's argument that this incentive is meaningless because of the availability of declaratory judgment relief is specious. Alza ignores the requirements for declaratory judgment subject matter jurisdiction that must be satisfied before such an action will be maintained. 7 Mr. Gary Buehler ROTHWELL, FIGG, ERNST & MANBECK Daniel E. Troy, Esq. April 2, 2004 Page 8 under Hatch-Waxman and FDA regulations, supported by past precedent. Such an absurd result would diminish the value of the 180-day generic drug exclusivity. Alza also protests that it is being somehow punished or penalized if pediatric exclusivity is not applied to Mylan's ANDA, and that Mylan is being "rewarded" for losing a patent suit. If Alza wanted the benefit of this statutory reward, all it had to do was abide by the statute and file its suit promptly. Instead, in an act of brinksmanship that was probably part of an effort to delay an adjudication of Mylan's patent contest until after the patent expired, Alza waited too long to file suit. This is not a question of punishment or penalty, it is a question of whether FDA should reward Alza with a Hatch-Waxman exclusivity when Alza did not to bring its lawsuit within the timeframe Hatch-Waxman prescribes as the quid pro quo for pediatric exclusivity. CONCLUSION Because Alza failed to sue within the statutory 45-day period, it is not entitled to the Hatch-Waxman exclusivities, including pediatric exclusivity, with respect to Mylan's ANDA. Mylan's ANDA received final approval, and the district court's order merely delayed the effective date of that approval to the expiration date of Alza's patent. Mylan is entitled to commence commercial marketing and sale of its generic product immediately upon expiration of Alza's patent. The district court's order does not direct FDA, who was not a party to the litigation, to do anything. No action by FDA is required to give effect to the district court's order. Respectfully submitted, /s/ E. Anthony Figg E. Anthony Figg cc: Peter O. Safir, Esq. ANDA 74-803 June 14, 2000 Barr Laboratories, Inc. Attention: Christine Mundkur 2 Quaker Road P.O. Box 2900 Pomona, NY 10970-0519 Dear Madam: This is in reference to your abbreviated new drug application dated December 9, 1995, submitted pursuant to Section 505(j) of the Federal Food, Drug, and Cosmetic Act (Act), for Fluoxetine Capsules USP, 10 mg and 20 mg. Reference is also made to your amendments dated June 6, 1997; April 29, June 15, and August 18, 1998; April 12, April 30, May 14, May 21, June 7, August 26, and December 17, 1999; and February 2, March 7, March 17, and April 18, 2000. Reference is also made to your correspondence dated March 13, March 14, and April 17, 1996. We have completed the review of this abbreviated application and have concluded that based upon the information you have presented to date, the drug is safe and effective for use as recommended in the submitted labeling. Therefore, the application is TENTATIVELY APPROVED. This determination is based upon information available to the Agency at this time (i.e., information in your application and the status of current good manufacturing practices (CGMPs) of the facilities used in the manufacture and testing of the drug product), and is subject to change on the basis of new information that may come to our attention. This letter does not address the notice issues related to the 180-day exclusivity provisions under section 505(j)(5)(B)(iv) of the Act. The listed drug product (RLD) referenced in your application, Prozac Capsules of Eli Lilly & Co., is subject to periods of patent protection which expire on February 2, 2001, (U.S. Patent No. 4,314,081 [the '081 patent]), and December 2, 2003, (U.S. Patent No. 4,626,549 [the '549 patent]). Your application contains a Paragraph IV Certification to the '081 and '549 patents under Section 505(j)(2)(A)(vii)(IV) of the Act stating that your manufacture, use, or sale of this drug product will not infringe on these patents or that the patents are invalid or unenforceable. You have notified the agency that Barr Laboratories, Inc. has complied with the notification requirements of Section 505(j)(2)(B) of the Act. Subsequently, the patent and NDA holder initiated a patent infringement suit against Barr et al. in the United States District Court for the Southern District of Indiana (Eli Lilly and Company v. Barr Laboratories, Inc., Apotex Inc., Interpharm Inc., Bernard C. Sherman, and Geneva Pharmaceuticals, Inc., Civil Action No. IP 96-0491C B/S). On January 25, 1999, the district court entered a Final Judgement and Injunction in this case which states that the '081 and '549 patents were not proven to be invalid or unenforceable and that Barr et al. infringed the patents by filing the ANDA. Furthermore, the district court prohibited the agency from approving any ANDA for this drug product subject to the injunction before the expiration of the '549 patent, subject to further rulings by the courts. You have informed the agency that the district court decision was appealed to the U.S. Court of Appeals, Federal Circuit in Washington, D.C., and that oral arguments were heard before this court on March 8, 2000. The Appeals Court's decision is currently pending. Because the Agency is granting a tentative approval for this application, please submit an amendment at least 60-days (but not more than 90-days) prior to the date you believe your application will be eligible for final approval. Your amendment should identify changes, if any, in the conditions under which the drug product was tentatively approved and should include documentation such as a copy of a final order or judgement from the Court of Appeals, or a settlement agreement between the parties, whichever is applicable, a licensing agreement between you and the patent holder, or any other relevant information. The amendment should also provide updated information such as final-printed labeling, chemistry, manufacturing and controls data as appropriate. As your amendment serves to reactivate this application in OGD, an amendment should be submitted even if no changes were made to the application since the date of this tentative approval letter. This amendment should be designated clearly in your cover letter as a MINOR AMENDMENT. In addition to this amendment, the agency may request at any time prior to the date of final approval that you submit an additional amendment containing the information described above. Failure to submit either or, if requested, both amendments, may result in rescission of the tentative approval status of your application, or may result in a delay in the issuance of the final approval letter. Any significant changes in the conditions outlined in this abbreviated application as well as changes in the status of the manufacturing and testing facilities' compliance with current good manufacturing practices (CGMPs) are subject to agency review before final approval of the application will be made. The drug product that is the subject of this abbreviated application may not be marketed without final Agency approval under section 505 of the Act. The introduction or delivery for introduction into interstate commerce of this drug before the effective final approval date is prohibited under section 501 of the Act. Also, until the Agency issues the final approval letter, this drug product will not be listed in the Agency's "Approved Drug Products with Therapeutic Equivalence Evaluations" list, (the "Orange Book"). Before you submit the amendment(s), please contact Timothy Ames, R.Ph., Project Manager, at (301) 827-5798, for further instructions. Sincerely yours, Gary Buehler Acting Director Office of Generic Drugs Center for Drug Evaluation and Research EX-99.2 4 j0675101exv99w2.txt LETTER TO THE FDA DATED MARCH 31, 2004 Exhibit 99.2 COVINGTON & BURLING 1201 PENNSYLVANIA AVENUE NW WASHINGTON PETER O. SAFIR WASHINGTON, DC 20004-2401 NEW YORK TEL 202.662.6000 SAN FRANCISCO TEL 202.662.5162 FAX 202.662.6291 LONDON FAX 202.778.5162 WWW.COV.COM BRUSSELS PSAFIR@COV.COM March 31, 2004 BY HAND DELIVERY Mr. Gary Buehler RECEIVED/DOCKETING Director, Office of Generic Drugs ROTHWELL FIGG ERNST & MANBECK United States Food and Drug Administration FILE NO.: 1592-410 286 Metro Park North II ------------------------- 7500 Standish Place DKT PROC. INIT. Ind Rockville, MD 20855 MAR 31 2004 Daniel E. Troy, Esq. DKT ENTRY INIT: Chief Counsel ------------------- United States Food and Drug Administration SEND TO: NVH 5600 Fishers Lane, GCF-1 -------------------------- Rockville, MD 20857 OK TO FILE: ----------------------- Re: Pediatric Extension for NDA #19-813 and Approval of ANDA #76-258 (fentanyl transdermal system) Dear Messers. Buehler and Troy: We write on behalf of ALZA Corporation to confirm that FDA will (1) pursuant to court Order, change the approval date of Mylan Technologies, Inc.'s ("Mylan") Abbreviated New Drug Application ("ANDA") #76-258, (fentanyl transdermal system) to no earlier than July 23, 2004, and (2) following the expiration of ALZA's U.S. Patent No. 4,588,580 (the "'580 patent"), apply the six-month pediatric extension granted to ALZA's Duragesic(R) fentanyl patch to Mylan's ANDA, thereby causing Mylan's ANDA to be approved no earlier than January 23, 2005. On March 25, 2004, the United States District Court for the District of Vermont held that the '580 patent was valid and infringed by Mylan's ANDA product. The court ordered that the effective date of Mylan's ANDA approval could not be earlier than the expiration of the '580 patent, or July 23, 2004. Under these circumstances, section 271(e)(4) in combination with longstanding FDA precedent requires that FDA convert Mylan's approval to tentative status. In addition, FDA's recent decision involving Ranbaxy and Pfizer, upheld in court, compels that Mylan's paragraph IV certification be converted to a paragraph II certification upon patent COVINGTON & BURLING expiration.(1) Thereupon, Mylan's ANDA cannot be approved prior to expiration of the six-month period of pediatric exclusivity that attaches to ALZA's NDA. BACKGROUND On July 15, 1999, FDA requested that ALZA, a subsidiary of Johnson & Johnson, evaluate the safety of using its Duragesic fentanyl transdermal patch in an opioid-tolerant pediatric patient population with chronic pain and to determine an appropriate dosing regimen in the same population. See Letter from John K. Jenkens, Director, Office of Drug Evaluation II, FDA, to Elizabeth M. Turek, Associate Director, Regulatory Affairs, Janssen Research Foundation (July 15, 1999) (attached as Exhibit C). ALZA undertook FDA's request, conducted extensive research, and, after substantial investment successfully completed clinical studies in pediatric populations. In May 2003, FDA approved ALZA's pediatric studies and granted ALZA six months of additional exclusivity after the expiration of ALZA's '580 patent. Thus, FDA extended ALZA's market exclusivity in Duragesic(R) from the patent expiration date of July 23, 2004, to the termination of pediatric exclusivity on January 23, 2005. Meanwhile, in November 2001, Mylan filed an ANDA for a fentanyl transdermal patch product. Mylan's ANDA included a paragraph IV certification claiming that ALZA's '580 patent covering Duragesic(R) was invalid and/or not infringed by Mylan's proposed ANDA product. On January 25, 2002, ALZA filed a patent infringement suit challenging Mylan's certification.(2) On March 25, 2004, the district court held that Mylan's ANDA product infringes ALZA's valid and enforceable '580 patent. See ALZA Corp. v. Mylan Labs., Inc., Consol. Case No. 2:02-cv-20, Judgment (D. Vt. Mar. 26, 2004) (attached as Exhibit D). The court recognized ALZA's entitlement to the pediatric extension, noting that "the FDA has extended Duragesic's period of market exclusivity for an additional six months from the expiration date of the '580 patent." See ALZA Corp. v. Mylan Labs., Inc., Consol. Case No. 2:02-cv-20, Findings of Fact at 18 (D. Vt. Mar. 25, 2004). Pursuant to ALZA's request and the statutory mandate, the court ordered that the effective date of Mylan's ANDA approval be not earlier than the expiration of the '580 patent. - --------------------- (1) Ranbaxy Labs. Ltd. v. FDA, Civ. Action No. 04-0133 (PLF), 2004 WL 440444, at *5 (D.D.C. Mar. 10, 2004) (attached as Exhibit A); see also Ranbaxy Labs. Ltd. v. FDA, No. 04-5079, Order (D.C. Cir. Mar. 24, 2004) (denying Ranbaxy's motion for a preliminary injunction pending appeal on the ground that, among other things, Ranbaxy "ha[d] not demonstrated...likelihood of success on the merits") (attached as Exhibit B). (2) A proposed generic may obtain FDA review during the term of a listed patent in two ways. First, the generic manufacturer may acknowledge, without challenge, the date of expiration of the listed patent (a "paragraph III" certification). 21 U.S.C. Section 355(j)(2)(A)(vii)(III). In that case, FDA may review the application and approve the generic on the date of patent expiration. Id. Section 355(j)(5)(B)(ii). Alternatively, the generic manufacturer may -- as Mylan did here -- challenge the validity or infringement of a listed patent (a "paragraph IV" certification). Id. Section 355(j)(2)(A)(vii)(IV). In that case, FDA may approve the application "immediately," unless the patent owner institutes litigation within a 45-day period, in which case final approval is blocked until the earlier of either the expiration of 30 months, or the court's resolution of the patent issue in favor of the ANDA applicant. Id. Section 355(j)(5)(B)(iii). 2 COVINGTON & BURLING Because Mylan certified to FDA that ALZA did not file its infringement suit within the 45-day period referred to in section 355(j)(5)(B) of the Federal Food, Drug, and Cosmetic Act ("FFDCA")(3), FDA was free to approve Mylan's ANDA at any time, and it did so on November 21, 2003. As is common in such cases, and notwithstanding its paragraph IV certification, Mylan elected not to launch its ANDA product at the time, thereby avoiding the risk of damages for wilful infringement. Indeed, to forestall any motion by ALZA for a preliminary injunction, Mylan agreed to give ALZA 45 days notice of any decision to launch. Now any launch is barred by the court's Order in ALZA's favor ruling that the effective date of Mylan's approval not be earlier than the date of expiration of the '580 patent. Pursuant to the court's Order, the issue of Mylan's approval is returned to the FDA. In these circumstances, FDA must (1) in compliance with the court's Order and FDA's own precedent, change its prior approval of Mylan's ANDA to tentative, and (2) change the effective date of its approval of Mylan's ANDA to January 23, 2005, reflecting ALZA's period of pediatric exclusivity. DISCUSSION I. FDA MUST CHANGE THE EFFECTIVE DATE OF MYLAN'S APPROVAL AND DEEM THAT APPROVAL TENTATIVE The law requires FDA to reset its final approval of Mylan's ANDA to a future date not earlier than the expiration of the '580 patent. 35 U.S.C. Section 271(e)(4). Under settled agency policy, that approval -- like any future approval -- is merely tentative and remains subject to final FDA action. The district court has ruled that ALZA's patent is valid and infringed by Mylan's ANDA product. The Hatch-Waxman Act provides that, regardless of whether a lawsuit is filed within the 45-day period, in the event of litigation in which the patent owner is successful, "the court shall order the effective date of any approval of the drug . . . involved in the infringement to be a date which is not earlier than the date of the expiration of the patent which has been infringed." 35 U.S.C. Section 271(e)(4)(A). In this way, Congress placed unsuccessful paragraph IV certifiers in the same position as paragraph III certifiers. Irrespective of whether or when an applicant has elected to challenge the patent, a generic drug that is conceded or found to infringe a valid patent cannot be approved by FDA, nor can an existing approval remain effective during the term of such patent. Although FDA has already approved Mylan's generic product, by virtue of the court's Order the effective date of FDA's approval of Mylan's ANDA must be reset for some future date, no earlier than expiration of the '580 patent. 35 U.S.C. Section 271(e)(4)(A). This resetting of FDA approval is precisely what Congress envisioned in these circumstances: - ------------------ (3)ALZA filed suit within 45 days of receipt of Mylan's notice by the responsible ALZA official. See U.C.C. Section 1-201(27)(2001) (under UCC notice valid when received by responsible official). Nonetheless, FDA determined (contrary to ALZA's analysis) that receipt by ALZA's mail service was sufficient to begin the running of the 45-day period. See Correspondence attached as Exhibit E. 3 COVINGTON & BURLING "If the infringing party has not begun commercial marketing of the drug, injunctive relief may be granted to prevent any commercial activity with the drug and the FDA would be mandated to make the effective date of any approved ANDA not earlier than the expiration date of the infringed patent... In the case where an ANDA had been approved, the order would mandate a change in the effective date." H.R. Rep. No. 98-857, pt. 1, at 46 (1984) (emphasis added). This result would also occur even if marketing of the generic had already begun. In that event: "If the infringing party has begun commercial marketing of a drug, damages and other monetary relief and an injunctive relief may be awarded... In addition, the FDA would be mandated to change the effective date of the approved ANDA to the expiration date of the infringed patent." H.R. Rep. No. 98-857, pt. 1, at 46 (1984) (emphasis added). It is common for an ANDA product to obtain a final approval from FDA, even while patent litigation is ongoing. Prior approval can occur where the innovator's lawsuit was filed after the 45-day period or where the 30-month stay has expired prior to the end of litigation. See Federal Trade Commission, "Generic Drug Entry Prior to Patent Expiration," at 15-16 (July 2002), available at www.ftc.gov/os/2002/07/genericdrugstudy.pdf (noting that in seven of seventy-five such suits, the 30-month stay expired before the district court rendered a decision). In either circumstance, FDA can, and has, given "final" approval to an ANDA product even while patent litigation continues. Thereafter, where a court eventually finds a patent to be valid and infringed and orders the effective date of an approved ANDA to be reset in the future, FDA routinely adjusts the effective date - turning the final approval into a tentative approval. Indeed, where FDA itself sets a delayed effective date for an ANDA approval, FDA regulations expressly provide that "an approval with a delayed effective date is tentative and does not become final until the effective date." 21 C.F.R. Section 314.105(d). The same result necessarily applies when the delay in approval is ordered by the court under the Hatch-Waxman Act. Indeed a generic applicant has no vested right in an ANDA approval whose effective date has been delayed. See Barr Labs., Inc. v. Thompson, 238 F. Supp. 2d 236,249 (D.D.C. 2002) (upholding FDA's position that "an ANDA approval cannot and should not be considered 'final' until the approval takes effect"). Moreover, the plain import of the court's Order (and the statutory command) that "the effective date of any approval of Mylan's ANDA product shall be no earlier than the date of the expiration" of the patent is to invoke the language of 21 C.F.R. Section 314.105(d) and to return the issue to FDA for consideration of what now must be viewed as a tentative approval, not a rote resetting of the date of a final approval. 4 COVINGTON & BURLING In a case involving Teva Pharmaceuticals USA, for example, the ANDA had received "final" approval four months prior to conclusion of the patent litigation. The eventual order in the patentee's favor "amended the judgment to indicate that the effective date of approval of [Teva's] ANDA is determined to be a date that is not earlier than the expiration date of the '516 patent." Implementing the court order, FDA determined that "the final approval...is hereby converted to a tentative approval." See, e.g., Letter from Gary J. Buehler, Director, Office of Generic Drugs, FDA, to Teva Pharmaceuticals USA, at 2 (Mar. 21, 2002), located at http://www.fda.gov/cder/foi/appletter/2002/74539ta3.pdf (attached as Exhibit F). To like effect, in a litigation involving Mylan Pharmaceuticals, the ANDA had received "final" approval at the end of the 30-month stay and prior to any decision in the patent infringement litigation. Thereafter, the patent litigation settled and Mylan changed its certification to paragraph III. FDA concluded that it had the power (and the duty) to change the approved ANDA to a tentative one. FDA reasoned: "Although Section 505(j) does not expressly provide for a change in approval status based upon the ANDA applicant's resolution of patent litigation, provisions of the 1984 Drug Price Competition and Price Term Restoration Act codified in the Patent Code give courts the authority to order the date of approval of an ANDA to be no earlier than the date of expiration of the infringed patent is described at 35 U.S.C. 271(e)(4). The legislative history of Hatch-Waxman makes it clear FDA may change the approval status of an approved ANDA based upon the outcome of patent infringement litigation." Letter from Gary J. Buehler to Mylan Pharmaceuticals, Inc., at 2 (Mar. 21, 2002), located at http://www.fda.gov/cder/foi/appletter/2002/74732ta3.pdf (attached as Exhibit G). And in the case of Barr Laboratories (against Ortho-McNeil Pharmaceutical, Inc.), whose ANDA received final approval after expiration of the 30-month stay but before a trial on the merits, FDA converted Barr's final approval of its ANDA to tentative, and applied the pediatric extension to that ANDA after the court entered a consent judgment containing a finding of infringement and validity of the innovator's patents. See, e.g., Letter to Gary J. Buehler, Director, Office of Generic Drugs, FDA from Ortho-McNeil Pharmaceutical, Inc. (Aug. 5, 2003), and print-outs from CDER Final and Tentative Approvals pages (reflecting final approval for Barr on December 18, 2002 but tentative approval on August 20, 2003)(attached as Exhibit H). There are important policy reasons to make an approval that is effective at a future date tentative only. Tentative status enables FDA to ensure that a generic applicant continues to satisfy all applicable criteria when outstanding barriers to approval are finally removed. See Letter from Gary J. Buehler, Director, Office of Generic Drugs, FDA, to Richard M. Cooper, Counsel to Ranbaxy Laboratories Ltd., at 5 (Jan. 28, 2004)(hereinafter "Ranbaxy Letter")(attached as Exhibit I)("There are many cases where a tentatively approved application will not be eligible for final approval at the moment the last patent barrier to approval expires."). "It is vital to FDA...that the interpretation of the [FFDCA] statute leave...space to reassess 5 COVINGTON & BURLING the application at the moment of approval to ensure that it is indeed consonant with the statutory criteria." Transcript of Motions Hearing, Ranbaxy Labs. Ltd. v. FDA, Civ. Action No. 04-0133, at 32 (D.D.C. Mar. 4, 2004) (attached as Exhibit J) (representation to the court of Daniel E. Troy, Esq., Chief Counsel to FDA). By requiring that FDA set Mylan's ANDA for final approval no sooner than patent expiration, the district court's Order compels FDA to change the existing approval that it granted to Mylan's ANDA in November 2003. And because the new approval date stands in the future, settled FDA policy mandates that the only approval for which Mylan can now be eligible is tentative. II. ALZA IS ENTITLED TO ITS PEDIATRIC EXTENSION AS TO MYLAN. Mylan infringed ALZA's valid and enforceable patent. Under 35 U.S.C. Section 271(e)(4)(A) and the court's Order, Mylan's ANDA approval -- the fruit of its infringement -- must now be withdrawn. Under these circumstances, both the statutory language and the Congressional policy underlying pediatric exclusivity mandate that Mylan be held to the same period of exclusivity that applies to all other ANDA applicants. With Mylan's approval converted into a tentative approval, FDA cannot give final approval until six months after the date of patent expiration. That is the intent of the pediatric extension, which Congress has accorded a higher priority than approval of generic products. As FDA recognized in its brief to the court in the Ranbaxy litigation: "In enacting the pediatric exclusivity provisions of FDAMA, Congress unequivocally trumped any claimed 'right' of generic applicants to be approved upon patent expiration where an NDA holder has conducted pediatric studies requested by the agency.... Rather, Congress expressed a clear intent to reward companies that had conducted the pediatric studies that FDA had requested." Fed. Defs.' Mem. in Opp. to Pls.' Motions for Prelim. Inj., Ranbaxy Labs. Ltd. v. FDA, Civ. Action No. 04-0133, at 36 (D.D.C. Feb. 20, 2004). The pediatric extension is implemented by statute in a variety of circumstances, depending upon the nature of the generic's certification. But whether the certification is under paragraph II, III or IV, Congress promised that the innovator who obtains pediatric approval will obtain an additional six months marketing exclusivity upon the expiration of its patent. National Pharmaceutical Alliance v Henney, 47 F. Supp. 2d 37, 38 (D.D.C. 1999). That is the result here regardless of the mode of analysis. PARAGRAPH IV. Six months exclusivity results directly from Mylan's existing paragraph IV certification. For a paragraph IV certification, the pediatric extension requires only that (1) "the drug [be] the subject of a listed patent for which a [paragraph IV] certification has been submitted" and (2) "in the infringement litigation resulting from the certification the court determines that the patent is valid and would be infringed." 21 U.S.C. Section 355a(c)(2)(B). Both of these predicates occurred here and that is all that is necessary. As FDA has recognized, referring 6 COVINGTON & BURLING to this provision, this "statutory language... explicitly provides what the outcome will be... where that ANDA applicant has been sued and the NDA holder or patent owner prevailed on the merits of the patent litigation. In that situation, pediatric exclusivity plainly attaches to the patent, and delays approval of the ANDA for six months." Fed. Defs.' Mem. in Opp. to Pls.' Motions for Prelim. Inj., Ranbaxy Labs. Ltd. v. FDA, Civ. Action No. 04-0133, at 35 (emphasis added).(4) PARAGRAPH III. In any event, Mylan's paragraph IV certification should be converted to a paragraph III certification. A paragraph IV certification may be sufficient to begin the ANDA review process, but it cannot trump the final judgment of the district court. Mylan may disagree with the court's ruling, but the final judgment both resolves in favor of ALZA the issues of validity and infringement and bars effective approval of Mylan's ANDA until after the expiration of the '580 patent. See 21 U.S.C. Sections 355(j)(2)(A)(vii)(IV), (j)(2)(B)(ii); 35 U.S.C. Section 271(e)(4)(A); cf. 21 C.F.R. Section 314.94(a)(12)(viii)(A) (2003). In these circumstances, Mylan's paragraph IV certification is invalid and should be corrected to paragraph III. FDA has, by regulation, expressly required an ANDA applicant to change its paragraph IV certification to paragraph III where the patent owner has sued within 45 days and prevails in the litigation. 21 C.F.R. Section 314.94(a)(12)(i))(A)(4). This regulation requires the change even where the applicant is appealing the adverse decision and even when the 30-month stay has expired. FDA's regulatory determination that in such circumstances a paragraph IV certification is misleading and should be corrected, should also apply to an ANDA applicant like Mylan whose certification to the FDA is found by a court to be inaccurate, pursuant to a final judgment of validity and infringement. Although this circumstance is not expressly addressed by the regulation, under section 314.94(a)(12)(i)(C), "an applicant shall amend a submitted certification if, at any time before the effective date of the approval of the application, the applicant learns that the submitted certification is no longer accurate." Mylan's certification is no longer accurate in light of the district court's findings, regardless of the date the lawsuit was - ------------------------- 4 Mylan argues that this congressionally intended result should not apply because the pediatric extension is somehow available only when the patent owner files suit within 45 days. In Mylan's analysis, the pediatric extension can only extend the 30 month stay, which Mylan equates with "the period during which [ANDA] may not be approved..." That reading is nonsensical. The language does not refer to the 30 month stay and nothing in the legislative history suggests that it does. Mylan does not explain how Congress' intent is achieved when the 30-month has expired or is never implemented. In fact, the reference to the "period during which an ANDA may not be approved" appears identically for paragraph II, III and IV certifications, even though a paragraph II certification (like a paragraph IV certification when no lawsuit is filed in 45 days) permits "immediate" approval of an ANDA. The language plainly means only that the date of approval "shall be extended by a period of six months after the date the patent expires..." and FDA has so interpreted the same language in the Ranbaxy case. By employing identical language in the paragraph II and paragraph IV contexts, Congress made clear that the extension applies upon patent expiration and extends the period - if any - during which an ANDA may not be approved. The statute contains several such intervals, including, for example, the 45-day period following notice of paragraph IV certification, id. Section 355(j)(5)(B)(iii), and the fundamental 180-day period allotted for FDA's review an NDA, id., Section 355(c). In this instance, the period is that between the court's decision in favor of ALZA and the expiration of the '580 patent. 7 COVINGTON & BURLING instituted. Mylan is obligated to convert its certification to paragraph III.(5) See Ranbaxy Labs. Ltd. v. FDA, Civ. Action No. 04-0133 (PLF), 2004 WL 440444, at *5(D.D.C. Mar. 10, 2004) (adopting FDA's interpretation that where a Paragraph IV certification became inaccurate, it created both an obligation on the applicant's part to amend its ANDA to reflect the change in circumstances (patent expiry) and an inability on the part of the FDA to approve the ANDAs in their inaccurate form). Thereupon, FDA cannot approve its ANDA product until six months after the expiration of the patent. PARAGRAPH II. Finally, and irrespective of whether Mylan's certification is currently accurate and supportable, Mylan's ANDA will not contain a paragraph IV (or paragraph III) certification when it ultimately becomes eligible for approval, after the expiration of the '580 patent. At that point in time, Mylan's ANDA will contain a paragraph II certification, which renders Mylan's ANDA indisputably subject to ALZA's six-month period of exclusivity. As set out above, Mylan's ANDA must now revert to tentative status. FDA's recent decision in the Ranbaxy case teaches that its status remains tentative until the expiration of ALZA's six-month grant of pediatric exclusivity. Because Mylan's paragraph IV (or paragraph III) certification lapses upon patent expiry, that certification does not alter this result. As FDA has recently explained, "[a]t the moment a patent listed as part of an NDA expires,... a paragraph IV certification previously submitted by an ANDA applicant to that patent is no longer valid (because there is no patent left to challenge)." Thus, the agency concluded, "[u]pon patent expiry, [a] paragraph IV certification becomes a paragraph II certification (indicating a patent has expired) by operation of law." Ranbaxy Letter, Exhibit I at 4. Under this analysis, when the '580 patent expires on July 23, 2004, Mylan's certification converts to a paragraph II certification. See id. ("FDA will consider the certification changed upon the expiration of the patent."); Ranbaxy Labs. Ltd. v. FDA, Civ. Action No. 04-0133 (PLF), 2004 WL 440444, at *5 (D.D.C. Mar. 10, 2004)(adopting FDA's interpretation and concluding that at patent expiry, "the Paragraph IV certifications became invalid, and either converted as a matter of law to Paragraph II certifications or became inaccurate, thereby creating both an obligation on [the applicant's] part to amend its ANDAs to reflect patent expiry and an inability on the part of the FDA to approve the ANDAs in their inaccurate form")(attached as Exhibit A); see also Dr. Reddy's Labs., Inc. v. Thompson, Civ. Action No. 02-452 (WGB) at 31-33 (D.N.J. Oct. 14, 2003)(upholding FDA requirement that paragraph IV certification be changed to paragraph II certification upon patent expiry). Whether after patent expiry Mylan on its own accord properly amends its certification to a certification under paragraph II, or whether instead that modification occurs as a matter of law, Mylan's ANDA will become eligible for approval only when it contains a paragraph II certification.(6) - -------------------- (5) Among other reasons for this change, Mylan should not be permitted to block approval of subsequent paragraph IV filers by maintaining paragraph IV status after a court determination of infringement. (6) Mylan suggests that its entitlement to approval "is not affected by post-litigation or post-expiration conversions of [a] certification[ ]." Mylan Letter at 6. Ranbaxy directly rejects this analysis. The relevant certification for purposes of approval and, in turn, for purposes of pediatric exclusivity is the one that is in place at the time of final approval. See, e.g., Ranbaxy Labs., 2004 WL 440444, at *5 (holding that, upon conversion of ANDA applicant's certification from paragraph IV to paragraph II, "the applicable provision of Section [355a] 8 COVINGTON & BURLING An ANDA that contains a paragraph II certification is unquestionably subject to the patent holder's period of pediatric exclusivity. Under the FFDCA, "[i]f the drug is the subject of . . . a listed patent for which a certification has been submitted under subsection . . . (j)(2)(A)(vii)(II) [Paragraph II] of section 355 of this title, THE PERIOD DURING WHICH AN APPLICATION MAY NOT BE APPROVED UNDER SECTION . . . 355(j)(4)(B) [sic](7) OF THIS TITLE SHALL BE EXTENDED BY A PERIOD OF SIX MONTHS AFTER THE DATE THE PATENT EXPIRES (including any patent extensions)." 21 U.S.C. Section 355a(c)(2)(A)(i) (emphasis added). Because Mylan's ANDA will contain a paragraph II certification when it becomes eligible for final, effective approval, that ANDA is subject to ALZA's pediatric exclusivity. III. MYLAN'S ARGUMENTS WOULD FRUSTRATE CONGRESSIONAL POLICY In its March 26, 2004, letter to FDA, Mylan insists that ALZA's entitlement to its pediatric extension depends entirely on whether ALZA filed suit in 45 days, thereby triggering a 30-month stay of approval. Letter from E. Anthony Figg to Gary Buehler, Director, Office of Generic Drugs, and Daniel E. Troy, Chief Counsel, FDA, at 3 (Mar. 26, 2004) (hereinafter "Mylan Letter"), available at http://www.sec.gov/Archives/edgar/data/69499/000095012804000330/ j0661901exv99w1.txt.(8) As set forth in detail above, Mylan's analysis is entirely incorrect as a matter of statutory and regulatory interpretation. Moreover, there is no conceivable basis in policy expressed by Congress to support such a result. Mylan's focus on the 30-month stay finds no support in the legislation history, which makes no reference whatsoever to a 30-month stay.(9) To the contrary, the conference report on the legislation states unequivocally, "when the [pediatric] studies are completed and - -------------------------------------------------------------------------------- became [355]a(c)(2)(A)(i)" -- the provision that applies when a drug is the subject of an ANDA containing a paragraph II certification). (7) The correct reference is to section 355(j)(5)(B). See Mova Pharm. Corp. v. Shalala, 140 F.3d 1060, 1062 n.l (D.C. Cir. 1998). (8) Mylan's focus on the date of ALZA's initiation of the patent litigation is a red herring: under Mylan's reasoning, ALZA could have faced precisely the situation that it confronts today even had it filed suit against Mylan within the 45-day window provided by section 505(j)(5)(B). The 30-month stay under section 505(j)(5)(B) would expire on June 6, 2004. Had a decision by the patent court remained pending, FDA would have been free as of that date to grant final, effective approval to Mylan's ANDA. It is that moment of freedom -- whether it comes to pass because the 30-month stay has expired, or instead because the stay simply never took effect -- that, according to Mylan, permanently exempts its infringing ANDA from the provisions governing pediatric exclusivity. To convert the expiration or absence of a 30-month stay into a windfall for an infringer would contravene the statutory mandate, FDA policy, and Congressional intent. (9) Pub. L. No. 105-115 (1997). The pediatric exclusivity provisions, which expired in 2002, were renewed and expanded under the "Best Pharmaceuticals for Children Act," Pub. L. No. 107-109, 115 Stat. 1408 (2002). 9 COVINGTON & BURLING accepted by the Secretary, then the sponsor or manufacturer will qualify for 6 months of extra market exclusivity" (emphasis added).(10) The period of pediatric exclusivity extends the patent's lawful monopoly period and has nothing to do with a stay for purposes of litigation. Mylan contends that permitting a patent owner to secure a period of pediatric exclusivity when that patent owner has not secured a 30-month stay would undermine Congress's "incentive to patent owners to bring patent infringement actions promptly." Mylan Letter at 5. This is baseless. Should a patent holder choose not to seek prompt resolution of its patent rights, the statute empowers the ANDA applicant to take the initiative by bringing an action for declaratory judgment. 21 U.S.C. Section 505(j)(5)(B)(iii).(11) Adoption of Mylan's arguments would turn the statute on its head: by losing the lawsuit, Mylan would obtain rights superior to those of paragraph III certifiers, to which the pediatric exclusivity would apply. Congress surely could not have intended that an adjudicated infringer of a valid patent would obtain a de facto six months of exclusivity over non-infringers solely by virtue of the date on which the infringer was sued. Nothing in the statute or its legislative history suggests this peculiar result. Moreover, this strange conclusion would frustrate Congressional intent. Congress's intent in enacting the pediatric exclusivity provisions -- to create meaningful incentives for manufacturers to conduct the studies necessary to obtain pediatric labeling -- would be thwarted if manufacturers who for any reason failed to file litigation within 45 days against a Paragraph IV ANDA applicant, were deprived of market exclusivity to which they were otherwise entitled. Any construction of the statute suggesting that pediatric exclusivity is contingent upon a patent owner's decision to take advantage of a stay provision could weaken the incentive to conduct costly and complicated pediatric research. Undercutting the incentives of pediatric exclusivity in this way would be inconsistent with Congressional intent and contrary to sound public policy. - ---------------- (10) H.R. Conf. Rep. 105-399, at 92 (1997). (11) Mylan's policy argument is particularly misplaced here, where ALZA filed suit promptly and missed the 45-day period (in FDA's view) only because of a good faith dispute about its calculation. 10 COVINGTON & BURLING CONCLUSION ALZA has proved that Mylan has infringed its valid patent. Moreover, ALZA has invested substantial resources to conduct the studies requested by FDA and, in so doing, earned pediatric exclusivity. FDA should reject Mylan's attempt to carve out for itself an exception to that period of exclusivity -- on the basis of its failed challenge to ALZA's '580 patent. FDA's prior decisions, most recently in the Ranbaxy case, instruct that FDA should convert to tentative the approval of Mylan's ANDA and allow it to become effective only after the expiration of six months of pediatric exclusivity. This is the only result that comports with prior agency decisions, the statute, and Congressional intent in enacting the pediatric exclusivity provisions. Sincerely, /s/ Peter O. Safir ------------------------------- Peter O. Safir Anthony Herman COVINGTON & BURLING 1201 Pennsylvania Avenue, N.W. Washington, D.C. 20004-2401 Telephone: (202) 662-6000 Facsimile: (202) 662-6291 cc: E. Anthony Figg, Esq. Elizabeth Dickinson, Esq. Kim Dettlebach, Esq. 11 -----END PRIVACY-ENHANCED MESSAGE-----

EX-99.1

                                                                    Exhibit 99.1

                                  LAW OFFICES
                        ROTHWELL, FIGG, ERNST & MANBECK
                           A PROFESSIONAL CORPORATION

G. FRANKLIN ROTHWELL          1425 K STREET, N.W.        MARTHA CASSIDY, Ph.D.
E. ANTHONY FIGG                    SUITE 800             ROBERT H. CAMERON
BARBARA G. ERNST             WASHINGTON, D.C. 20005      THOMAS E. McKIERNAN
HARRY F. MANBECK, JR.                                    MICHAEL J. MORAN, Ph.D.
GEORGE R. REPPER            TELEPHONE (202) 783-6040     ANNE M. STERBA
STEVEN LIEBERMAN            FACSIMILE (202) 783-6031     LISA N. PHILLIPS*
VINCENT M. DeLUCA             www.rothwellfigg.com       LEIGH Z. CALLANDER
JOSEPH A. HYNDS                                          C. NICHOLE GIFFORD
ELIZABETH A. LEFF                                        REGINA A. BAILEY
RICHARD WYDEVEN                  April 2, 2004           MONICA S. DAVIS*
MARTIN M. ZOLTICK                                        PATRICK T. SKACEL
MINAKSI BHATT           VIA FACSIMILE AND HAND DELIVERY  BRIAN S. ROSENBLOOM
MICHAEL G. SULLIVAN                                      TARA J. PATE
SHARON L. DAVIS                                          MONICA C. KITTS
ROBERT B. MURRAY                                         BRIAN A. TOLLEFSON*
CARLA C. CALCAGNO                                        JOYCE H. A. VON NATZMER
JEFFREY L. IHNEN                                         JOO MEE KIM*
GLENN E. KARTA                                           CHRISTOPHER M. DURKEE
                                                         STEVEN M. GIOVANNETTI*
OF COUNSEL
                                                         *NOT ADMITTED IN D.C.
STEPHEN B. PARKER
JOHN A. McCAHILL
BARBARA WEBB WALKER


Gary J. Buehler
Director, Office of Generic Drugs
Center for Drug Evaluation and Research
Food and Drug Administration
MPN II, HFD-600
7500 Standish Place
Rockville, MD 20855

Daniel E. Troy, Esq.
Chief Counsel
Food and Drug Administration
5600 Fishers Lane, GCF-1
Rockville, MD 20857

     RE: MYLAN TECHNOLOGIES INC. ANDA NO. 76-258

Dear Messrs. Buehler and Troy:

     On March 26, 2004, we wrote on behalf of Mylan Technologies Inc. ("Mylan")
to explain why pediatric exclusivity does not apply to Mylan's already-approved
ANDA. Alza Corporation ("Alza") is not entitled to the regulatory exclusivities
of the Hatch-Waxman amendments, because it did not sue Mylan within the 45-day
statutory period after receiving Mylan's notice of a Paragraph IV certification.
Contrary to Alza' argument, so-called pediatric exclusivity is not a patent term
extension. Instead, this exclusivity is in the form of a stay of regulatory
approval that Congress grafted into the regulatory stays already embodied in
Hatch-Waxman. Entitlement to pediatric exclusivity is statutorily predicated on
compliance with the 45-day deadline for initiating patent infringement
litigation. This result is clear under the statute because:

     -    Mylan submitted an ANDA containing a Paragraph IV certification to
          Alza's Orange-Book-listed patent number 4,588,580 (the "580 Patent")
          and properly served Alza with notice of that certification pursuant
          to 21 U.S.C. Section 355(j)(2)(A)(vii)(IV).



                                                                Mr. Gary Buehler
ROTHWELL, FIGG, ERNST & MANBECK                             Daniel E. Troy, Esq.
                                                                   April 2, 2004
                                                                          Page 2

          -  Because Alza did not sue Mylan within 45 days (a fact confirmed by
             the FDA in the letter attached to Mylan's March 26, 2004 letter),
             Alza lost the benefit of any otherwise applicable Hatch-Waxman
             exclusivities and Mylan's ANDA became approvable effective
             "immediately." 21 U.S.C. Section 355(j)(5)(B).

          -  FDA was cognizant of this fact and issued a final approval of
             Mylan's ANDA, not a tentative approval, on November 21, 2003.

          -  The Hatch-Waxman provision governing application of so-called
             "pediatric exclusivity" in cases in which a Paragraph IV
             certification has been submitted is 21 U.S.C. Section
             355a(c)(2)(B), and no other. This provision expressly defines
             pediatric exclusivity as an extension of "the period during which
             an application may not be approved under section 505(c)(3) or
             section 505(j)(5)(B)," the latter of which applies to ANDAs, like
             Mylan's, containing Paragraph IV certifications. This provision
             does not extend the patent expiration date.

          -  In the case of ANDAs containing Paragraph IV certifications,
             section 355(j)(5)(B) defines "the period during which an
             application may not be approved" as the 30-month period commencing
             with receipt of the applicant's notice or until a court decision
             finding the patent valid and infringed. (Referred to herein for
             convenience as the 30-month period.) As the FDA has already
             recognized by its granting final approval to Mylan, no such period
             ever existed in this case. Thus, there is no period that can be
             "extended" through pediatric exclusivity.

          -  Although Alza asked the district court in post-trial briefs to
             apply its pediatric exclusivity to Mylan, the district court's
             March 25, 2004 order merely delays the effective date of Mylan's
             final approval until the '580 patent expires on July 23, 2004.

          -  The district court's order did not create a period during which
             Mylan's application may not be approved "under section 505(c)(3) or
             section 505(j)(5)(B)." Instead, it merely put into effect a delay
             of Mylan's final approval under 35 U.S.C. Section 271(e)(4)(A).

     On March 31, 2004, Alza's counsel submitted a letter asserting, in
summary, that: (i) Mylan's final approval must be revoked and FDA must "deem"
the final approval to be a "tentative approval"; (ii) Mylan must then be
compelled to change its Paragraph IV certification to a Paragraph III or
Paragraph II certification, because Mylan's Paragraph IV certification
ostensibly is no longer accurate; and (iii) Alza should be rewarded with an
additional six months of post-patent Hatch-Waxman pediatric exclusivity as to
Mylan (even though Alza abandoned all


                                       2

                                                                Mr. Gary Buehler
ROTHWELL, FIGG, ERNST & MANBECK                             Daniel E. Troy, Esq.
                                                                   April 2, 2004
                                                                          Page 3

Hatch-Waxman exclusivities by failing to sue within 45 days) because to enforce
the statute as written would "frustrate Congressional policy." Alza is wrong.

(1)  THERE IS NO REASON FOR FDA TO REVOKE MYLAN'S FINAL APPROVAL.

     The FDA has granted final approval of Mylan's ANDA. The district court's
order did not and could not revoke Mylan's final approval. It did nothing more
than delay the effective date of that approval to the expiration date of Alza's
patent, pursuant to 35 U.S.C. Section 271(e)(4)(A). Mylan, will, of course,
comply with the court's order until its injunctive effect ends upon patent
expiration, unless it is overturned earlier on appeal.

     Alza's statement at page 6 of its letter that "the district court's Order
compels FDA to change the existing approval" has no basis. The district court,
adopting the language of the statute, merely ordered that "the effective date of
any approval of Mylan's ANDA product shall be no earlier than the date of the
expiration of the '580 patent family [July 23, 2004]." The order does not direct
FDA - not a party to the litigation - to do anything, and there is no need for
FDA to do anything to give effect to the district court's order. The order is
directed to Mylan and mandates when Mylan's approval shall become effective.
Alza further argues that the effective date of Mylan's ANDA approval "must be
reset." But it already has been reset by the district court to the date of
patent expiration, July 23, 2004.

     The legislative history cited by Alza in page 4 of its letter (H.R. Rep.
No. 98-857, pt. 1, at 46 (1984)) actually undercuts Alza's assertions. It does
not reflect an intention by Congress that FDA needs to reset the effective date
of an approval in a case such as this. Instead, it says that if commercial
marketing has not begun the court's order would change the effective date of
the approval.

     Alza's reliance on the Teva, Mylan and Barr situations to support its
contention that Mylan's finally approved ANDA must be converted to a tentative
approval also is without merit. First, the Teva, Mylan and Barr cases are all
easily distinguishable. Unlike the present case, in each of those cases the
ANDA applicants were sued within 45 days. Each of those applicants voluntarily
submitted Paragraph III certifications after an adverse decision was entered by
a district court. Moreover, Barr settled its lawsuit with a final and binding
stipulation that the patent in suit was valid and infringed. None of those
circumstances exist here.

     Second, contrary to Alza's assertion, none of the Teva, Mylan and Barr
situations recognize or constitute any FDA authority to convert Mylan's final
approval to a tentative approval. In the letter sent to Mylan, the FDA expressly
stated that it was Mylan's voluntary submission of the Paragraph III
certification that enabled FDA to convert Mylan's ANDA approval to a tentative
approval. (See Ex. G to Alza's 3/31/04 letter). Likewise, in the letter sent to
Teva, the FDA expressly stated that the conversion of final approval to a
tentative approval was based on both the court order and the applicant's change
in certification. (See Ex. F to Alza's 3/31/04 letter). Thus, it was the
applicant's decisions voluntarily to change their

                                       3

                                                                Mr. Gary Buehler
                                                            Daniel E. Troy, Esq.
ROTHWELL, FIGG, ERNST & MANBECK                                    April 2, 2004
                                                                          Page 4


certifications to Paragraph III certifications (and, in the case of Barr, to
settle litigation with a final and binding stipulation of validity and
infringement) that caused the change in the status of approval to a tentative
approval, and not the fact that the ANDAs had delayed effective approval dates,
as Alza contends.

     Here, Mylan was not sued within 45 days. Under the applicable regulation,
21 C.F.R. section 314.94(a)(12)(viii)(A), Mylan is not required to change its
patent certification --a certification that is still factually accurate in view
of Mylan's intention to seek appellate review of the district court decision.
Adopting Alza's theory that ANDA applicants must change their certification to a
Paragraph III certification when they receive an adverse decision in the
district court would eviscerate the ANDA applicants' appeal rights. Under Alza's
theory, Mylan's certification should now be deemed a Paragraph III certification
and pediatric exclusivity applied through the end of six months after patent
expiration under section 355a(c)(2)(A). Therefore, under Alza's theory, Mylan
and similarly situated ANDA applicants who lose in the district court but then
win on appeal would nonetheless still be subject to pediatric exclusivity as if
they were originally Paragraph III filers. That would be an absurd result
because if Mylan wins its appeal, Alza cannot be entitled to pediatric
exclusivity based on an invalid or noninfringed patent.

     Alza does not provide a single example in its 11 page letter of any
instance in which FDA has converted a finally approved ANDA to tentative
approval over the objection of an applicant based on a district court opinion
and before the appeal process has been exhausted.

     Moreover, even if a change of Mylan's approval to a tentative approval were
appropriate, which it clearly is not, that change would not alter the fact that
Alza's pediatric exclusivity does not apply to Mylan. Pediatric exclusivity is
governed by section 355a(c)(2)(B), the applicability of which has nothing to do
with the status of the approval.

     Alza also says at page 5 that there are "important policy reasons" to
revoke Mylan's final approval because doing so would enable FDA to ensure that
Mylan "continues to satisfy all applicable criteria when outstanding barriers to
approval are finally removed." That argument is circular. There are no
"outstanding barriers to approval" unless the approval is revoked. Further, FDA
always has the authority to police Mylan's compliance with relevant statutory
and regulatory criteria for maintaining its approval, and FDA does not need to
revoke Mylan's approval in order to determine whether Mylan is compliant.

     In short, there is no need for FDA to do anything to give effect to the
court's order, much less take the extraordinary step of revoking a final
approval, and Alza has not supplied any precedent for FDA to take such action.

          (2)  MYLAN CANNOT BE REQUIRED TO CONVERT ITS PARAGRAPH IV
CERTIFICATION.

     Alza writes at page 7 of its letter that "Mylan's Paragraph IV
certification should be converted to a Paragraph III certification." Later in
the same paragraph, Alza asks FDA to


                                       4


                                                                Mr. Gary Buehler
                                                            Daniel E. Troy, Esq.
                                                                   April 2, 2004
                                                                          Page 5
ROTHWELL, FIGG, ERNST & MANBECK


"correct" Mylan's certification to a Paragraph III certification. That would be
contrary to law. "[T]here is no statutory provision which grants to the FDA,
either expressly or implicitly, the authority to change a 'IV certification' to
a 'III certification.'" Mylan v. Thompson, 207 F.Supp.2d 476, 487 (N.D.
W.Va.2001). Alza acknowledges that FDA's regulation concerning conversion from a
Paragraph IV certification to a Paragraph III certification, 21 C.F.R. Section
314.94(a)(12)(viii)(A), is expressly limited to situations in which the NDA
holder has filed suit within 45 days and so does not apply here.

     Nor is Mylan's Paragraph IV certification inaccurate. The statute requires
Mylan to certify as to its opinion with respect to the listed patent. Mylan's
good faith belief that the '580 patent is invalid, unenforceable and not
infringed has not changed as a result of the district court's decision. Mylan
will appeal that decision, on grounds that it was based on clear errors of law
and fact. As stated above, Mylan's right to appeal is very important. If Mylan
wins, Alza cannot be entitled to pediatric exclusivity based on an invalid or
noninfringed patent.

     Contrary to Alza's argument, the FDA does not require a change in the
patent certification when a district court has entered a finding of infringement
and validity. For example, Barr was not required to convert its Paragraph IV
certification to a Paragraph III certification upon receipt of an unfavorable
district court decision in its litigation with Eli Lilly involving fluoxetine
(Prozac(R)). See attached FDA letter. Barr maintained its Paragraph IV
certification and ultimately prevailed on appeal. The agency has recognized that
to require such a change would inappropriately cause the first Paragraph IV
filer to lose its 180-day exclusivity with respect to other ANDA applicants.

     (3) ALZA ABANDONED ANY RIGHT TO PEDIATRIC EXCLUSIVITY AS TO MYLAN.

     As discussed in our March 26 letter, pediatric exclusivity is not a patent
term extension, it is a type of Hatch-Waxman market exclusivity that is
applicable only in narrow circumstances defined by statute. One fundamental
trade-off under Hatch-Waxman is that an NDA holder must sue within the statutory
45-day period in order to avail itself of Hatch-Waxman exclusivities. Alza did
not do so and thereby abandoned any claim to pediatric exclusivity as to Mylan's
ANDA.

     Alza protests at page 6 of its letter that it is entitled to pediatric
exclusivity because of the district court's ruling and because of the "intent"
underlying Congress's "promise" of pediatric exclusivity. Of course, Congress
expresses its "intent" and makes "promises" in only one way: by enacting a
statute. Where is the language of a statute is clear, it is plain error for an
agency to depart from that statutory language in order to give effect to what
someone thinks Congress meant to say or should have or could have said. Chevron
U.S.A., Inc. v. Natural Resources Defense Council, Inc., 467 U.S. 837, 81 L. Ed.
2d 694, 104 S. Ct. 2778 (1984). That is exactly what Alza is asking FDA to do.



                                       5

ROTHWELL, FIGG, ERNST & MANBECK                                 Mr. Gary Buehler
                                                            Daniel E. Troy, Esq.
                                                                   April 2, 2004
                                                                          Page 6


     The text of section 355a(c)(2)(B) clearly provides that, when, as here, a
Paragraph IV certification has been submitted and a court has found the patent
to be valid and infringed, pediatric exclusivity is available only as a
post-patent expiration extension of "the period during which an application may
not be approved under section 505(c)(3) or section 505(j)(5)(B)." 21 U.S.C.
Section 355a(c)(2)(B). Because Alza failed to initiate suit within the
statutory 45-day period, there never was such "a period" during which the
application could not be approved, so there is no period to extend.

     Alza contends that "[s]ix months exclusivity results directly from Mylan's
existing Paragraph IV certification" because, according to Alza, section
355a(c)(2)(B) requires only a Paragraph IV certification and a finding of
infringement. (Alza's letter at 6). Alza, however, ignored the statutory
language defining pediatric exclusivity as an extension of the period during
which the application could not be approved under section 355(j)(5)(B). Alza
also conveniently leaves out of its analysis that there never was such a period
because it did not sue within 45 days. Alza's discussion of the provisions of
section 355(j)(5)(B) that relate to certifications under Paragraphs II and III
is inapposite. There is no dispute that the certification that Mylan provided
was properly under Paragraph IV. The period during which an application
containing a Paragraph IV certification may not be approved under section
355(j)(5)(B) is the 30-month period - which never existed in this case.

     Alza finally addresses its failure to meet the 45-day deadline in footnote
4 on page 7 of its letter. It argues that section 355(c)(2)(B) "does not refer
to the 30 month stay." This argument is wrong and ignores the language of the
statute. The statute explicitly defines pediatric exclusivity as a post-patent
extension of "the period during which an application may not be approved
under... section 505(j)(5)(B)," which is the 30-month stay provision. Because
that period did not exist here, Mylan's application was eligible for immediate
final approval, which was granted on November 21, 2003.

     Alza also argues that it is entitled to pediatric exclusivity under
sections dealing with Paragraph II and III certifications because Mylan's ANDA
ostensibly should be corrected or deemed to include a Paragraph II or III
certification. As discussed in part (2) above, there is no lawful basis to
require Mylan to change its Paragraph IV certification. Moreover, a Paragraph IV
certification "has been submitted," so section 355(c)(2)(B) expressly applies.

     (4) THIS CASE IS VERY DIFFERENT FROM RANBAXY.

     Alza improperly relies on the district court's decision in Ranbaxy Labs
Ltd. v. FDA. Ranbaxy was a case about pediatric exclusivity, but any similarity
ends there.

     In Ranbaxy, suit was filed by the NDA holder within 45 days. There was a
30-month stay in effect and, thus, there was a period during which Ranbaxy's
application could not be approved under section 355(j)(5)(B). In Ranbaxy, the
application had never been finally approved; only a tentative approval had been
granted and Ranbaxy was taking the position that



                                       6


                                                                Mr. Gary Buehler
                                                            Daniel E. Troy, Esq.
                                                                   April 2, 2004
                                                                          Page 7

Rothwell, Figg, Ernst & Manbeck

FDA is required, as a matter of course, to issue a final approval immediately
upon patent expiration without regard for FDA's continuing discretion to review
the application. There are no such considerations here. Further, there never
was a court decision finding the patent valid and infringed; the case had been
dismissed as moot upon expiration of the patent in suit. For all of those
reasons, section 355a(c)(2)(B) was not even at issue in Ranbaxy.

     (5) ADOPTING ALZA'S POSITION WOULD RENDER THE 45-DAY PERIOD MEANINGLESS.

     The public's interest in accelerating the availability of generic drugs to
American consumers sits at Hatch-Waxman's core. The legislation balances that
public interest against the intellectual property rights of NDA holders. The
45-day filing provision is central to this carefully-crafted Congressional
compromise and balance, but Alza's position, if adopted, would render it
essentially meaningless.

     Hatch-Waxman provides for periods of exclusivity to NDA holders that are
separate and apart from whatever rights they may have under the patent laws.
These non-patent exclusivities include the 30-month stay of approval under
section 355(j)(5)(B) and six months of post-patent pediatric exclusivity under
section 355a. As discussed above and in our March 26, 2004 letter,
Hatch-Waxman's statutory quid pro quo for these exclusivities in a case where a
Paragraph IV certification has been submitted is that the NDA holder/patentee
must file suit within 45 days after receiving a notice letter. The statutory
purpose behind that 45-day filing deadline is obvious. It encourages prompt
suits so patent issues can be resolved quickly and so generic applicants will
not face potentially catastrophic suits for damages which would otherwise be
brought at a later time, such as after a final approval has been granted and
the generic applicant is preparing for a market launch.(1) That strategy, if
successful, could add years to the time it takes for the generic company to
clear patent hurdles and bring a generic drug to market.

     If FDA adopts Alza's position that pediatric exclusivity may be applied to
Mylan's ANDA notwithstanding Alza's failure to sue Mylan on time, the most
powerful economic incentive for a branded pharmaceutical company to file suit
within 45 days will be lost. The single 30-month stay of approval available
under current law does not provide sufficient enticement for a prompt suit.
Generics are already seeing branded companies choose not to file suit within 45
days for strategic reasons, then resisting declaratory judgment jurisdiction
when generic applicants seek to join issue on the patents. Six months of extra,
post-patent market exclusivity, on the other hand, provides a huge economic
incentive to file suit promptly. That incentive will be gone if FDA agrees with
Alza.

     In addition, adoption of Alza's position would result in every ANDA
applicant with a Paragraph IV certification having to change its patent
certification upon a district court decision finding the patent to be valid or
infringed. This is completely contrary to statutory provisions


- ---------------------
(1) Alza's argument that this incentive is meaningless because of the
availability of declaratory judgment relief is specious. Alza ignores the
requirements for declaratory judgment subject matter jurisdiction that must be
satisfied before such an action will be maintained.



                                       7

                                                                Mr. Gary Buehler
ROTHWELL, FIGG, ERNST & MANBECK                             Daniel E. Troy, Esq.
                                                                   April 2, 2004
                                                                          Page 8


under Hatch-Waxman and FDA regulations, supported by past precedent. Such an
absurd result would diminish the value of the 180-day generic drug exclusivity.

     Alza also protests that it is being somehow punished or penalized if
pediatric exclusivity is not applied to Mylan's ANDA, and that Mylan is being
"rewarded" for losing a patent suit. If Alza wanted the benefit of this
statutory reward, all it had to do was abide by the statute and file its suit
promptly. Instead, in an act of brinksmanship that was probably part of an
effort to delay an adjudication of Mylan's patent contest until after the
patent expired, Alza waited too long to file suit. This is not a question of
punishment or penalty, it is a question of whether FDA should reward Alza with
a Hatch-Waxman exclusivity when Alza did not to bring its lawsuit within the
timeframe Hatch-Waxman prescribes as the quid pro quo for pediatric exclusivity.

                                   CONCLUSION

     Because Alza failed to sue within the statutory 45-day period, it is not
entitled to the Hatch-Waxman exclusivities, including pediatric exclusivity,
with respect to Mylan's ANDA. Mylan's ANDA received final approval, and the
district court's order merely delayed the effective date of that approval to
the expiration date of Alza's patent. Mylan is entitled to commence commercial
marketing and sale of its generic product immediately upon expiration of Alza's
patent. The district court's order does not direct FDA, who was not a party to
the litigation, to do anything. No action by FDA is required to give effect to
the district court's order.

                                   Respectfully submitted,

                                   /s/ E. Anthony Figg

                                   E. Anthony Figg

cc:  Peter O. Safir, Esq.


ANDA 74-803                                                        June 14, 2000



Barr Laboratories, Inc.
Attention: Christine Mundkur
2 Quaker Road
P.O. Box 2900
Pomona, NY 10970-0519


Dear Madam:

This is in reference to your abbreviated new drug application dated December 9,
1995, submitted pursuant to Section 505(j) of the Federal Food, Drug, and
Cosmetic Act (Act), for Fluoxetine Capsules USP, 10 mg and 20 mg.

Reference is also made to your amendments dated June 6, 1997; April 29, June
15, and August 18, 1998; April 12, April 30, May 14, May 21, June 7, August 26,
and December 17, 1999; and February 2, March 7, March 17, and April 18, 2000.
Reference is also made to your correspondence dated March 13, March 14, and
April 17, 1996.

We have completed the review of this abbreviated application and have concluded
that based upon the information you have presented to date, the drug is safe
and effective for use as recommended in the submitted labeling. Therefore, the
application is TENTATIVELY APPROVED. This determination is based upon
information available to the Agency at this time (i.e., information in your
application and the status of current good manufacturing practices (CGMPs) of
the facilities used in the manufacture and testing of the drug product), and is
subject to change on the basis of new information that may come to our
attention. This letter does not address the notice issues related to the
180-day exclusivity provisions under section 505(j)(5)(B)(iv) of the Act.

The listed drug product (RLD) referenced in your application, Prozac Capsules of
Eli Lilly & Co., is subject to periods of patent protection which expire on
February 2, 2001, (U.S. Patent No. 4,314,081 [the '081 patent]), and December 2,
2003, (U.S. Patent No. 4,626,549 [the '549 patent]). Your application

contains a Paragraph IV Certification to the '081 and '549 patents under
Section 505(j)(2)(A)(vii)(IV) of the Act stating that your manufacture, use, or
sale of this drug product will not infringe on these patents or that the
patents are invalid or unenforceable. You have notified the agency that Barr
Laboratories, Inc. has complied with the notification requirements of Section
505(j)(2)(B) of the Act. Subsequently, the patent and NDA holder initiated a
patent infringement suit against Barr et al. in the United States District
Court for the Southern District of Indiana (Eli Lilly and Company v. Barr
Laboratories, Inc., Apotex Inc., Interpharm Inc., Bernard C. Sherman, and
Geneva Pharmaceuticals, Inc., Civil Action No. IP 96-0491C B/S). On January 25,
1999, the district court entered a Final Judgement and Injunction in this case
which states that the '081 and '549 patents were not proven to be invalid or
unenforceable and that Barr et al. infringed the patents by filing the ANDA.
Furthermore, the district court prohibited the agency from approving any ANDA
for this drug product subject to the injunction before the expiration of the
'549 patent, subject to further rulings by the courts. You have informed the
agency that the district court decision was appealed to the U.S. Court of
Appeals, Federal Circuit in Washington, D.C., and that oral arguments were
heard before this court on March 8, 2000. The Appeals Court's decision is
currently pending.

Because the Agency is granting a tentative approval for this application,
please submit an amendment at least 60-days (but not more than 90-days) prior
to the date you believe your application will be eligible for final approval.
Your amendment should identify changes, if any, in the conditions under which
the drug product was tentatively approved and should include documentation such
as a copy of a final order or judgement from the Court of Appeals, or a
settlement agreement between the parties, whichever is applicable, a licensing
agreement between you and the patent holder, or any other relevant information.
The amendment should also provide updated information such as final-printed
labeling, chemistry, manufacturing and controls data as appropriate. As your
amendment serves to reactivate this application in OGD, an amendment should be
submitted even if no changes were made to the application since the date of
this tentative approval letter. This amendment should be designated clearly in
your cover letter as a MINOR AMENDMENT. In addition to this amendment, the
agency may request at any time prior to the date of final approval that you
submit an additional amendment containing the information described above.
Failure to submit either or, if requested, both amendments, may result in
rescission of the tentative approval status of your



application, or may result in a delay in the issuance of the final approval
letter.

Any significant changes in the conditions outlined in this abbreviated
application as well as changes in the status of the manufacturing and testing
facilities' compliance with current good manufacturing practices (CGMPs) are
subject to agency review before final approval of the application will be made.

The drug product that is the subject of this abbreviated application may not be
marketed without final Agency approval under section 505 of the Act. The
introduction or delivery for introduction into interstate commerce of this drug
before the effective final approval date is prohibited under section 501 of the
Act. Also, until the Agency issues the final approval letter, this drug product
will not be listed in the Agency's "Approved Drug Products with Therapeutic
Equivalence Evaluations" list, (the "Orange Book").

Before you submit the amendment(s), please contact Timothy Ames, R.Ph., Project
Manager, at (301) 827-5798, for further instructions.

                              Sincerely yours,



                              Gary Buehler
                              Acting Director
                              Office of Generic Drugs
                              Center for Drug Evaluation and Research

EX-99.2

                                                                    Exhibit 99.2

COVINGTON & BURLING

1201 PENNSYLVANIA AVENUE NW    WASHINGTON           PETER O. SAFIR
WASHINGTON, DC 20004-2401      NEW YORK
TEL 202.662.6000               SAN FRANCISCO        TEL 202.662.5162
FAX 202.662.6291               LONDON               FAX 202.778.5162
WWW.COV.COM                    BRUSSELS             PSAFIR@COV.COM


                                                                  March 31, 2004


BY HAND DELIVERY

Mr. Gary Buehler                                    RECEIVED/DOCKETING
Director, Office of Generic Drugs              ROTHWELL FIGG ERNST & MANBECK
United States Food and Drug Administration   FILE NO.: 1592-410
286 Metro Park North II                               -------------------------
7500 Standish Place                          DKT PROC. INIT.  Ind
Rockville, MD 20855
                                                        MAR 31 2004
Daniel E. Troy, Esq.                         DKT ENTRY INIT:
Chief Counsel                                               -------------------
United States Food and Drug Administration   SEND TO:  NVH
5600 Fishers Lane, GCF-1                             --------------------------
Rockville, MD 20857                          OK TO FILE:
                                                        -----------------------
     Re:  Pediatric Extension for NDA #19-813 and Approval of ANDA #76-258
          (fentanyl transdermal system)

Dear Messers. Buehler and Troy:

          We write on behalf of ALZA Corporation to confirm that FDA will (1)
pursuant to court Order, change the approval date of Mylan Technologies, Inc.'s
("Mylan") Abbreviated New Drug Application ("ANDA") #76-258, (fentanyl
transdermal system) to no earlier than July 23, 2004, and (2) following the
expiration of ALZA's U.S. Patent No. 4,588,580 (the "'580 patent"), apply the
six-month pediatric extension granted to ALZA's Duragesic(R) fentanyl patch to
Mylan's ANDA, thereby causing Mylan's ANDA to be approved no earlier than
January 23, 2005.

          On March 25, 2004, the United States District Court for the District
of Vermont held that the '580 patent was valid and infringed by Mylan's ANDA
product. The court ordered that the effective date of Mylan's ANDA approval
could not be earlier than the expiration of the '580 patent, or July 23, 2004.
Under these circumstances, section 271(e)(4) in combination with longstanding
FDA precedent requires that FDA convert Mylan's approval to tentative status.
In addition, FDA's recent decision involving Ranbaxy and Pfizer, upheld in
court, compels that Mylan's paragraph IV certification be converted to a
paragraph II certification upon patent

COVINGTON & BURLING

expiration.(1) Thereupon, Mylan's ANDA cannot be approved prior to expiration
of the six-month period of pediatric exclusivity that attaches to ALZA's NDA.

                                   BACKGROUND

     On July 15, 1999, FDA requested that ALZA, a subsidiary of Johnson &
Johnson, evaluate the safety of using its Duragesic fentanyl transdermal patch
in an opioid-tolerant pediatric patient population with chronic pain and to
determine an appropriate dosing regimen in the same population. See Letter from
John K. Jenkens, Director, Office of Drug Evaluation II, FDA, to Elizabeth M.
Turek, Associate Director, Regulatory Affairs, Janssen Research Foundation (July
15, 1999) (attached as Exhibit C). ALZA undertook FDA's request, conducted
extensive research, and, after substantial investment successfully completed
clinical studies in pediatric populations. In May 2003, FDA approved ALZA's
pediatric studies and granted ALZA six months of additional exclusivity after
the expiration of ALZA's '580 patent. Thus, FDA extended ALZA's market
exclusivity in Duragesic(R) from the patent expiration date of July 23, 2004, to
the termination of pediatric exclusivity on January 23, 2005.

     Meanwhile, in November 2001, Mylan filed an ANDA for a fentanyl
transdermal patch product. Mylan's ANDA included a paragraph IV certification
claiming that ALZA's '580 patent covering Duragesic(R) was invalid and/or not
infringed by Mylan's proposed ANDA product. On January 25, 2002, ALZA filed a
patent infringement suit challenging Mylan's certification.(2)

     On March 25, 2004, the district court held that Mylan's ANDA product
infringes ALZA's valid and enforceable '580 patent. See ALZA Corp. v. Mylan
Labs., Inc., Consol. Case No. 2:02-cv-20, Judgment (D. Vt. Mar. 26, 2004)
(attached as Exhibit D). The court recognized ALZA's entitlement to the
pediatric extension, noting that "the FDA has extended Duragesic's period of
market exclusivity for an additional six months from the expiration date of the
'580 patent." See ALZA Corp. v. Mylan Labs., Inc., Consol. Case No. 2:02-cv-20,
Findings of Fact at 18 (D. Vt. Mar. 25, 2004). Pursuant to ALZA's request and
the statutory mandate, the court ordered that the effective date of Mylan's
ANDA approval be not earlier than the expiration of the '580 patent.


- ---------------------
(1)  Ranbaxy Labs. Ltd. v. FDA, Civ. Action No. 04-0133 (PLF), 2004 WL 440444,
at *5 (D.D.C. Mar. 10, 2004) (attached as Exhibit A); see also Ranbaxy Labs.
Ltd. v. FDA, No. 04-5079, Order (D.C. Cir. Mar. 24, 2004) (denying Ranbaxy's
motion for a preliminary injunction pending appeal on the ground that, among
other things, Ranbaxy "ha[d] not demonstrated...likelihood of success on the
merits") (attached as Exhibit B).

(2)  A proposed generic may obtain FDA review during the term of a listed
patent in two ways. First, the generic manufacturer may acknowledge, without
challenge, the date of expiration of the listed patent (a "paragraph III"
certification). 21 U.S.C. Section 355(j)(2)(A)(vii)(III). In that case, FDA may
review the application and approve the generic on the date of patent
expiration. Id. Section 355(j)(5)(B)(ii). Alternatively, the generic
manufacturer may -- as Mylan did here -- challenge the validity or infringement
of a listed patent (a "paragraph IV" certification). Id. Section
355(j)(2)(A)(vii)(IV). In that case, FDA may approve the application
"immediately," unless the patent owner institutes litigation within a 45-day
period, in which case final approval is blocked until the earlier of either the
expiration of 30 months, or the court's resolution of the patent issue in favor
of the ANDA applicant. Id. Section 355(j)(5)(B)(iii).


                                       2

COVINGTON & BURLING

          Because Mylan certified to FDA that ALZA did not file its
infringement suit within the 45-day period referred to in section 355(j)(5)(B)
of the Federal Food, Drug, and Cosmetic Act ("FFDCA")(3), FDA was free to
approve Mylan's ANDA at any time, and it did so on November 21, 2003. As is
common in such cases, and notwithstanding its paragraph IV certification, Mylan
elected not to launch its ANDA product at the time, thereby avoiding the risk
of damages for wilful infringement. Indeed, to forestall any motion by ALZA for
a preliminary injunction, Mylan agreed to give ALZA 45 days notice of any
decision to launch. Now any launch is barred by the court's Order in ALZA's
favor ruling that the effective date of Mylan's approval not be earlier than
the date of expiration of the '580 patent.

          Pursuant to the court's Order, the issue of Mylan's approval is
returned to the FDA. In these circumstances, FDA must (1) in compliance with
the court's Order and FDA's own precedent, change its prior approval of Mylan's
ANDA to tentative, and (2) change the effective date of its approval of Mylan's
ANDA to January 23, 2005, reflecting ALZA's period of pediatric exclusivity.

                                   DISCUSSION

I.   FDA MUST CHANGE THE EFFECTIVE DATE OF MYLAN'S APPROVAL AND DEEM THAT
     APPROVAL TENTATIVE

          The law requires FDA to reset its final approval of Mylan's ANDA to a
future date not earlier than the expiration of the '580 patent. 35 U.S.C.
Section 271(e)(4). Under settled agency policy, that approval -- like any
future approval -- is merely tentative and remains subject to final FDA action.

          The district court has ruled that ALZA's patent is valid and
infringed by Mylan's ANDA product. The Hatch-Waxman Act provides that,
regardless of whether a lawsuit is filed within the 45-day period, in the event
of litigation in which the patent owner is successful, "the court shall order
the effective date of any approval of the drug . . . involved in the
infringement to be a date which is not earlier than the date of the expiration
of the patent which has been infringed." 35 U.S.C. Section 271(e)(4)(A). In
this way, Congress placed unsuccessful paragraph IV certifiers in the same
position as paragraph III certifiers. Irrespective of whether or when an
applicant has elected to challenge the patent, a generic drug that is conceded
or found to infringe a valid patent cannot be approved by FDA, nor can an
existing approval remain effective during the term of such patent.

          Although FDA has already approved Mylan's generic product, by virtue
of the court's Order the effective date of FDA's approval of Mylan's ANDA must
be reset for some future date, no earlier than expiration of the '580 patent.
35 U.S.C. Section 271(e)(4)(A). This resetting of FDA approval is precisely
what Congress envisioned in these circumstances:


- ------------------
(3)ALZA filed suit within 45 days of receipt of Mylan's notice by the
responsible ALZA official. See U.C.C. Section 1-201(27)(2001) (under UCC notice
valid when received by responsible official). Nonetheless, FDA determined
(contrary to ALZA's analysis) that receipt by ALZA's mail service was
sufficient to begin the running of the 45-day period. See Correspondence
attached as Exhibit E.



                                       3

COVINGTON & BURLING

               "If the infringing party has not begun commercial
               marketing of the drug, injunctive relief may be
               granted to prevent any commercial activity with
               the drug and the FDA would be mandated to make the
               effective date of any approved ANDA not earlier
               than the expiration date of the infringed
               patent... In the case where an ANDA had been
               approved, the order would mandate a change in the
               effective date."

H.R. Rep. No. 98-857, pt. 1, at 46 (1984) (emphasis added).

               This result would also occur even if marketing of the generic
had already begun. In that event:

               "If the infringing party has begun commercial
               marketing of a drug, damages and other monetary
               relief and an injunctive relief may be awarded...
               In addition, the FDA would be mandated to change
               the effective date of the approved ANDA to the
               expiration date of the infringed patent."

H.R. Rep. No. 98-857, pt. 1, at 46 (1984) (emphasis added).

               It is common for an ANDA product to obtain a final approval from
FDA, even while patent litigation is ongoing. Prior approval can occur where
the innovator's lawsuit was filed after the 45-day period or where the 30-month
stay has expired prior to the end of litigation. See Federal Trade Commission,
"Generic Drug Entry Prior to Patent Expiration," at 15-16 (July 2002),
available at www.ftc.gov/os/2002/07/genericdrugstudy.pdf (noting that in seven
of seventy-five such suits, the 30-month stay expired before the district court
rendered a decision). In either circumstance, FDA can, and has, given "final"
approval to an ANDA product even while patent litigation continues.

               Thereafter, where a court eventually finds a patent to be valid
and infringed and orders the effective date of an approved ANDA to be reset in
the future, FDA routinely adjusts the effective date - turning the final
approval into a tentative approval. Indeed, where FDA itself sets a delayed
effective date for an ANDA approval, FDA regulations expressly provide that "an
approval with a delayed effective date is tentative and does not become final
until the effective date." 21 C.F.R. Section 314.105(d). The same result
necessarily applies when the delay in approval is ordered by the court under the
Hatch-Waxman Act. Indeed a generic applicant has no vested right in an ANDA
approval whose effective date has been delayed. See Barr Labs., Inc. v.
Thompson, 238 F. Supp. 2d 236,249 (D.D.C. 2002) (upholding FDA's position that
"an ANDA approval cannot and should not be considered 'final' until the approval
takes effect"). Moreover, the plain import of the court's Order (and the
statutory command) that "the effective date of any approval of Mylan's ANDA
product shall be no earlier than the date of the expiration" of the patent is to
invoke the language of 21 C.F.R. Section 314.105(d) and to return the issue to
FDA for consideration of what now must be viewed as a tentative approval, not a
rote resetting of the date of a final approval.


                                       4



COVINGTON & BURLING

     In a case involving Teva Pharmaceuticals USA, for example, the ANDA had
received "final" approval four months prior to conclusion of the patent
litigation. The eventual order in the patentee's favor "amended the judgment to
indicate that the effective date of approval of [Teva's] ANDA is determined to
be a date that is not earlier than the expiration date of the '516 patent."
Implementing the court order, FDA determined that "the final approval...is
hereby converted to a tentative approval." See, e.g., Letter from Gary J.
Buehler, Director, Office of Generic Drugs, FDA, to Teva Pharmaceuticals USA,
at 2 (Mar. 21, 2002), located at
http://www.fda.gov/cder/foi/appletter/2002/74539ta3.pdf (attached as Exhibit F).

     To like effect, in a litigation involving Mylan Pharmaceuticals, the ANDA
had received "final" approval at the end of the 30-month stay and prior to any
decision in the patent infringement litigation. Thereafter, the patent
litigation settled and Mylan changed its certification to paragraph III. FDA
concluded that it had the power (and the duty) to change the approved ANDA to a
tentative one. FDA reasoned:

                    "Although Section 505(j) does not expressly provide for a
                    change in approval status based upon the ANDA applicant's
                    resolution of patent litigation, provisions of the 1984 Drug
                    Price Competition and Price Term Restoration Act codified in
                    the Patent Code give courts the authority to order the date
                    of approval of an ANDA to be no earlier than the date of
                    expiration of the infringed patent is described at 35 U.S.C.
                    271(e)(4). The legislative history of Hatch-Waxman makes it
                    clear FDA may change the approval status of an approved ANDA
                    based upon the outcome of patent infringement litigation."

Letter from Gary J. Buehler to Mylan Pharmaceuticals, Inc., at 2 (Mar. 21,
2002), located at http://www.fda.gov/cder/foi/appletter/2002/74732ta3.pdf
(attached as Exhibit G).

     And in the case of Barr Laboratories (against Ortho-McNeil Pharmaceutical,
Inc.), whose ANDA received final approval after expiration of the 30-month stay
but before a trial on the merits, FDA converted Barr's final approval of its
ANDA to tentative, and applied the pediatric extension to that ANDA after the
court entered a consent judgment containing a finding of infringement and
validity of the innovator's patents. See, e.g., Letter to Gary J. Buehler,
Director, Office of Generic Drugs, FDA from Ortho-McNeil Pharmaceutical, Inc.
(Aug. 5, 2003), and print-outs from CDER Final and Tentative Approvals pages
(reflecting final approval for Barr on December 18, 2002 but tentative approval
on August 20, 2003)(attached as Exhibit H).

     There are important policy reasons to make an approval that is effective at
a future date tentative only. Tentative status enables FDA to ensure that a
generic applicant continues to satisfy all applicable criteria when outstanding
barriers to approval are finally removed. See Letter from Gary J. Buehler,
Director, Office of Generic Drugs, FDA, to Richard M. Cooper, Counsel to Ranbaxy
Laboratories Ltd., at 5 (Jan. 28, 2004)(hereinafter "Ranbaxy Letter")(attached
as Exhibit I)("There are many cases where a tentatively approved application
will not be eligible for final approval at the moment the last patent barrier to
approval expires."). "It is vital to FDA...that the interpretation of the
[FFDCA] statute leave...space to reassess


                                       5

COVINGTON & BURLING

the application at the moment of approval to ensure that it is indeed consonant
with the statutory criteria." Transcript of Motions Hearing, Ranbaxy Labs. Ltd.
v. FDA, Civ. Action No. 04-0133, at 32 (D.D.C. Mar. 4, 2004) (attached as
Exhibit J) (representation to the court of Daniel E. Troy, Esq., Chief Counsel
to FDA).

     By requiring that FDA set Mylan's ANDA for final approval no sooner than
patent expiration, the district court's Order compels FDA to change the
existing approval that it granted to Mylan's ANDA in November 2003. And because
the new approval date stands in the future, settled FDA policy mandates that
the only approval for which Mylan can now be eligible is tentative.

II. ALZA IS ENTITLED TO ITS PEDIATRIC EXTENSION AS TO MYLAN.

     Mylan infringed ALZA's valid and enforceable patent. Under 35 U.S.C.
Section 271(e)(4)(A) and the court's Order, Mylan's ANDA approval -- the fruit
of its infringement -- must now be withdrawn. Under these circumstances, both
the statutory language and the Congressional policy underlying pediatric
exclusivity mandate that Mylan be held to the same period of exclusivity that
applies to all other ANDA applicants.

     With Mylan's approval converted into a tentative approval, FDA cannot give
final approval until six months after the date of patent expiration. That is
the intent of the pediatric extension, which Congress has accorded a higher
priority than approval of generic products. As FDA recognized in its brief to
the court in the Ranbaxy litigation:

          "In enacting the pediatric exclusivity provisions of FDAMA, Congress
          unequivocally trumped any claimed 'right' of generic applicants to be
          approved upon patent expiration where an NDA holder has conducted
          pediatric studies requested by the agency.... Rather, Congress
          expressed a clear intent to reward companies that had conducted the
          pediatric studies that FDA had requested."

Fed. Defs.' Mem. in Opp. to Pls.' Motions for Prelim. Inj., Ranbaxy Labs. Ltd.
v. FDA, Civ. Action No. 04-0133, at 36 (D.D.C. Feb. 20, 2004).

     The pediatric extension is implemented by statute in a variety of
circumstances, depending upon the nature of the generic's certification. But
whether the certification is under paragraph II, III or IV, Congress promised
that the innovator who obtains pediatric approval will obtain an additional six
months marketing exclusivity upon the expiration of its patent. National
Pharmaceutical Alliance v Henney, 47 F. Supp. 2d 37, 38 (D.D.C. 1999).

     That is the result here regardless of the mode of analysis.

     PARAGRAPH IV. Six months exclusivity results directly from Mylan's
existing paragraph IV certification. For a paragraph IV certification, the
pediatric extension requires only that (1) "the drug [be] the subject of a
listed patent for which a [paragraph IV] certification has been submitted" and
(2) "in the infringement litigation resulting from the certification the court
determines that the patent is valid and would be infringed." 21 U.S.C. Section
355a(c)(2)(B). Both of these predicates occurred here and that is all that is
necessary. As FDA has recognized, referring

                                       6


COVINGTON & BURLING

to this provision, this "statutory language... explicitly provides what the
outcome will be... where that ANDA applicant has been sued and the NDA holder or
patent owner prevailed on the merits of the patent litigation. In that
situation, pediatric exclusivity plainly attaches to the patent, and delays
approval of the ANDA for six months." Fed. Defs.' Mem. in Opp. to Pls.' Motions
for Prelim. Inj., Ranbaxy Labs. Ltd. v. FDA, Civ. Action No. 04-0133, at 35
(emphasis added).(4)

     PARAGRAPH III. In any event, Mylan's paragraph IV certification should be
converted to a paragraph III certification. A paragraph IV certification may be
sufficient to begin the ANDA review process, but it cannot trump the final
judgment of the district court. Mylan may disagree with the court's ruling, but
the final judgment both resolves in favor of ALZA the issues of validity and
infringement and bars effective approval of Mylan's ANDA until after the
expiration of the '580 patent. See 21 U.S.C. Sections 355(j)(2)(A)(vii)(IV),
(j)(2)(B)(ii); 35 U.S.C. Section 271(e)(4)(A); cf. 21 C.F.R. Section
314.94(a)(12)(viii)(A) (2003). In these circumstances, Mylan's paragraph IV
certification is invalid and should be corrected to paragraph III.

     FDA has, by regulation, expressly required an ANDA applicant to change its
paragraph IV certification to paragraph III where the patent owner has sued
within 45 days and prevails in the litigation. 21 C.F.R. Section
314.94(a)(12)(i))(A)(4). This regulation requires the change even where the
applicant is appealing the adverse decision and even when the 30-month stay has
expired. FDA's regulatory determination that in such circumstances a paragraph
IV certification is misleading and should be corrected, should also apply to an
ANDA applicant like Mylan whose certification to the FDA is found by a court to
be inaccurate, pursuant to a final judgment of validity and infringement.
Although this circumstance is not expressly addressed by the regulation, under
section 314.94(a)(12)(i)(C), "an applicant shall amend a submitted certification
if, at any time before the effective date of the approval of the application,
the applicant learns that the submitted certification is no longer accurate."
Mylan's certification is no longer accurate in light of the district court's
findings, regardless of the date the lawsuit was


- -------------------------

4    Mylan argues that this congressionally intended result should not apply
because the pediatric extension is somehow available only when the patent owner
files suit within 45 days. In Mylan's analysis, the pediatric extension can only
extend the 30 month stay, which Mylan equates with "the period during which
[ANDA] may not be approved..." That reading is nonsensical. The language does
not refer to the 30 month stay and nothing in the legislative history suggests
that it does. Mylan does not explain how Congress' intent is achieved when the
30-month has expired or is never implemented.

     In fact, the reference to the "period during which an ANDA may not be
approved" appears identically for paragraph II, III and IV certifications, even
though a paragraph II certification (like a paragraph IV certification when no
lawsuit is filed in 45 days) permits "immediate" approval of an ANDA. The
language plainly means only that the date of approval "shall be extended by a
period of six months after the date the patent expires..." and FDA has so
interpreted the same language in the Ranbaxy case.

     By employing identical language in the paragraph II and paragraph IV
contexts, Congress made clear that the extension applies upon patent expiration
and extends the period - if any - during which an ANDA may not be approved. The
statute contains several such intervals, including, for example, the 45-day
period following notice of paragraph IV certification, id. Section
355(j)(5)(B)(iii), and the fundamental 180-day period allotted for FDA's review
an NDA, id., Section 355(c). In this instance, the period is that between the
court's decision in favor of ALZA and the expiration of the '580 patent.



                                       7


COVINGTON & BURLING

instituted. Mylan is obligated to convert its certification to paragraph III.(5)
See Ranbaxy Labs. Ltd. v. FDA, Civ. Action No. 04-0133 (PLF), 2004 WL 440444, at
*5(D.D.C. Mar. 10, 2004) (adopting FDA's interpretation that where a Paragraph
IV certification became inaccurate, it created both an obligation on the
applicant's part to amend its ANDA to reflect the change in circumstances
(patent expiry) and an inability on the part of the FDA to approve the ANDAs in
their inaccurate form). Thereupon, FDA cannot approve its ANDA product until six
months after the expiration of the patent.

     PARAGRAPH II. Finally, and irrespective of whether Mylan's certification is
currently accurate and supportable, Mylan's ANDA will not contain a paragraph IV
(or paragraph III) certification when it ultimately becomes eligible for
approval, after the expiration of the '580 patent. At that point in time,
Mylan's ANDA will contain a paragraph II certification, which renders Mylan's
ANDA indisputably subject to ALZA's six-month period of exclusivity. As set out
above, Mylan's ANDA must now revert to tentative status. FDA's recent decision
in the Ranbaxy case teaches that its status remains tentative until the
expiration of ALZA's six-month grant of pediatric exclusivity. Because Mylan's
paragraph IV (or paragraph III) certification lapses upon patent expiry, that
certification does not alter this result. As FDA has recently explained, "[a]t
the moment a patent listed as part of an NDA expires,... a paragraph IV
certification previously submitted by an ANDA applicant to that patent is no
longer valid  (because there is no patent left to challenge)." Thus, the agency
concluded, "[u]pon patent expiry, [a] paragraph IV certification becomes a
paragraph II certification (indicating a patent has expired) by operation of
law." Ranbaxy Letter, Exhibit I at 4.

     Under this analysis, when the '580 patent expires on July 23, 2004, Mylan's
certification converts to a paragraph II certification. See id. ("FDA will
consider the certification changed upon the expiration of the patent."); Ranbaxy
Labs. Ltd. v. FDA, Civ. Action No. 04-0133 (PLF), 2004 WL 440444, at *5 (D.D.C.
Mar. 10, 2004)(adopting FDA's interpretation and concluding that at patent
expiry, "the Paragraph IV certifications became invalid, and either converted as
a matter of law to Paragraph II certifications or became inaccurate, thereby
creating both an obligation on [the applicant's] part to amend its ANDAs to
reflect patent expiry and an inability on the part of the FDA to approve the
ANDAs in their inaccurate form")(attached as Exhibit A); see also Dr. Reddy's
Labs., Inc. v. Thompson, Civ. Action No. 02-452 (WGB) at 31-33 (D.N.J. Oct. 14,
2003)(upholding FDA requirement that paragraph IV certification be changed to
paragraph II certification upon patent expiry).

     Whether after patent expiry Mylan on its own accord properly amends its
certification to a certification under paragraph II, or whether instead that
modification occurs as a matter of law, Mylan's ANDA will become eligible for
approval only when it contains a paragraph II certification.(6)


- --------------------
(5)  Among other reasons for this change, Mylan should not be permitted to block
approval of subsequent paragraph IV filers by maintaining paragraph IV status
after a court determination of infringement.

(6)  Mylan suggests that its entitlement to approval "is not affected by
post-litigation or post-expiration conversions of [a] certification[      ]."
Mylan Letter at 6. Ranbaxy directly rejects this analysis. The relevant
certification for purposes of approval and, in turn, for purposes of pediatric
exclusivity is the one that is in place at the time of final approval. See,
e.g., Ranbaxy Labs., 2004 WL 440444, at *5 (holding that, upon conversion of
ANDA applicant's certification from paragraph IV to paragraph II, "the
applicable provision of Section [355a]


                                       8

COVINGTON & BURLING

          An ANDA that contains a paragraph II certification is unquestionably
subject to the patent holder's period of pediatric exclusivity. Under the FFDCA,

          "[i]f the drug is the subject of . . . a listed patent
          for which a certification has been submitted under
          subsection . . . (j)(2)(A)(vii)(II) [Paragraph II] of
          section 355 of this title, THE PERIOD DURING WHICH AN
          APPLICATION MAY NOT BE APPROVED UNDER SECTION . . .
          355(j)(4)(B) [sic](7) OF THIS TITLE SHALL BE EXTENDED
          BY A PERIOD OF SIX MONTHS AFTER THE DATE THE PATENT
          EXPIRES (including any patent extensions)."

21 U.S.C. Section 355a(c)(2)(A)(i) (emphasis added). Because Mylan's ANDA will
contain a paragraph II certification when it becomes eligible for final,
effective approval, that ANDA is subject to ALZA's pediatric exclusivity.

III.  MYLAN'S ARGUMENTS WOULD
      FRUSTRATE CONGRESSIONAL POLICY

          In its March 26, 2004, letter to FDA, Mylan insists that ALZA's
entitlement to its pediatric extension depends entirely on whether ALZA filed
suit in 45 days, thereby triggering a 30-month stay of approval. Letter from
E. Anthony Figg to Gary Buehler, Director, Office of Generic Drugs, and Daniel
E. Troy, Chief Counsel, FDA, at 3 (Mar. 26, 2004) (hereinafter "Mylan Letter"),
available at http://www.sec.gov/Archives/edgar/data/69499/000095012804000330/
j0661901exv99w1.txt.(8) As set forth in detail above, Mylan's analysis is
entirely incorrect as a matter of statutory and regulatory interpretation.
Moreover, there is no conceivable basis in policy expressed by Congress to
support such a result.

          Mylan's focus on the 30-month stay finds no support in the
legislation history, which makes no reference whatsoever to a 30-month stay.(9)
To the contrary, the conference report on the legislation states unequivocally,
"when the [pediatric] studies are completed and

- --------------------------------------------------------------------------------
became [355]a(c)(2)(A)(i)" -- the provision that applies when a drug is the
subject of an ANDA containing a paragraph II certification).

(7)  The correct reference is to section 355(j)(5)(B). See Mova Pharm. Corp. v.
Shalala, 140 F.3d 1060, 1062 n.l (D.C. Cir. 1998).

(8)  Mylan's focus on the date of ALZA's initiation of the patent litigation is
a red herring: under Mylan's reasoning, ALZA could have faced precisely the
situation that it confronts today even had it filed suit against Mylan within
the 45-day window provided by section 505(j)(5)(B). The 30-month stay under
section 505(j)(5)(B) would expire on June 6, 2004. Had a decision by the patent
court remained pending, FDA would have been free as of that date to grant
final, effective approval to Mylan's ANDA. It is that moment of freedom --
whether it comes to pass because the 30-month stay has expired, or instead
because the stay simply never took effect -- that, according to Mylan,
permanently exempts its infringing ANDA from the provisions governing pediatric
exclusivity. To convert the expiration or absence of a 30-month stay into a
windfall for an infringer would contravene the statutory mandate, FDA policy,
and Congressional intent.

(9)  Pub. L. No. 105-115 (1997). The pediatric exclusivity provisions, which
expired in 2002, were renewed and expanded under the "Best Pharmaceuticals for
Children Act," Pub. L. No. 107-109, 115 Stat. 1408 (2002).


                                       9

COVINGTON & BURLING

accepted by the Secretary, then the sponsor or manufacturer will qualify for 6
months of extra market exclusivity" (emphasis added).(10) The period of
pediatric exclusivity extends the patent's lawful monopoly period and has
nothing to do with a stay for purposes of litigation.

     Mylan contends that permitting a patent owner to secure a period of
pediatric exclusivity when that patent owner has not secured a 30-month stay
would  undermine Congress's "incentive to patent owners to bring patent
infringement actions promptly." Mylan Letter at 5. This is baseless. Should a
patent holder choose not to seek prompt resolution of its patent rights, the
statute empowers the ANDA applicant to take the initiative by bringing an action
for declaratory judgment. 21 U.S.C. Section 505(j)(5)(B)(iii).(11)

     Adoption of Mylan's arguments would turn the statute on its head: by losing
the lawsuit, Mylan would obtain rights superior to those of paragraph III
certifiers, to which the pediatric exclusivity would apply. Congress surely
could not have intended that an adjudicated infringer of a valid patent would
obtain a de facto six months of exclusivity over non-infringers solely by virtue
of the date on which the infringer was sued. Nothing in the statute or its
legislative history suggests this peculiar result.

     Moreover, this strange conclusion would frustrate Congressional intent.
Congress's intent in enacting the pediatric exclusivity provisions -- to create
meaningful incentives for manufacturers to conduct the studies necessary to
obtain pediatric labeling -- would be thwarted if manufacturers who for any
reason failed to file litigation within 45 days against a Paragraph IV ANDA
applicant, were deprived of market exclusivity to which they were otherwise
entitled. Any construction of the statute suggesting that pediatric exclusivity
is contingent upon a patent owner's decision to take advantage of a stay
provision could weaken the incentive to conduct costly and complicated pediatric
research. Undercutting the incentives of pediatric exclusivity in this way would
be inconsistent with Congressional intent and contrary to sound public policy.





- ----------------
(10)   H.R. Conf. Rep. 105-399, at 92 (1997).

(11)   Mylan's policy argument is particularly misplaced here, where ALZA filed
suit promptly and missed the 45-day period (in FDA's view) only because of a
good faith dispute about its calculation.


                                       10

COVINGTON & BURLING

                                   CONCLUSION

          ALZA has proved that Mylan has infringed its valid patent. Moreover,
ALZA has invested substantial resources to conduct the studies requested by FDA
and, in so doing, earned pediatric exclusivity. FDA should reject Mylan's
attempt to carve out for itself an exception to that period of exclusivity --
on the basis of its failed challenge to ALZA's '580 patent. FDA's prior
decisions, most recently in the Ranbaxy case, instruct that FDA should convert
to tentative the approval of Mylan's ANDA and allow it to become effective only
after the expiration of six months of pediatric exclusivity. This is the only
result that comports with prior agency decisions, the statute, and
Congressional intent in enacting the pediatric exclusivity provisions.

                                        Sincerely,



                                        /s/ Peter O. Safir
                                        -------------------------------
                                        Peter O. Safir
                                        Anthony Herman
                                        COVINGTON & BURLING
                                        1201 Pennsylvania Avenue, N.W.
                                        Washington, D.C. 20004-2401
                                        Telephone: (202) 662-6000
                                        Facsimile: (202) 662-6291


cc:  E. Anthony Figg, Esq.
     Elizabeth Dickinson, Esq.
     Kim Dettlebach, Esq.


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