The United States Court of Appeals for the Federal Circuit found in favor of Eisai in Aciphex patent infringement suit against Teva Pharmaceuticals and Dr. Reddy’s Laboratories .  Eisai v. Dr. Reddy’s and Teva (07-1397/98)

After Eisai filed infringement actions contesting Teva Pharmaceuticals and Dr. Reddy’s Laboratories’ submission of abbreviated new drug applications (ANDAs) to the Food and Drug Administration for Aciphex (rabeprazole), the district court found that Dr. Reddy’s and Teva failed to prove the remaining allegations of inequitable conduct and that Eisai had established that Dr. Reddy’s and Teva infringed Eisai’s patent (US 5,045,552).

The ’552 patent claims rabeprazole and its salts.  Rabeprazole is part of a class of drugs known as proton pump inhibitors, which suppress gastric acid production by inhibiting action of the enzyme H+K+ATPase.  Rabeprazole’s sodium salt is the active ingredient in Aciphex, a pharmaceutical approved for the treatment of duodenal ulcers, heartburn, and associated disorders.  Aciphex has over $1 billion in worldwide yearly sales.

Dr. Reddy’s and Teva each filed Abbreviated New Drug Applications (ANDAs) under the Hatch-Waxman Act looking to manufacture a generic version of Aciphex before the expiration of the ’552 patent.

The factual determinations of obviousness include 1) the scope and content of the prior art, 2) the level of ordinary skill in the art, 3) the differences between the claimed invention and the prior art, and 4) evidence of secondary factors, also known as objective indicia of non-obviousness.  Where the patent at issue claims a chemical compound, the analysis of the third Graham factor (the differences between the claimed invention and the prior art) often turns on the structural similarities and differences between the claimed compound and the prior art compounds.

The court stated:

Obviousness based on structural similarity thus can be proved by identification of some motivation that would have led one of ordinary skill in the art to select and then modify a known compound (i.e. a lead compound) in a particular way to achieve the claimed compound.  See Takeda Chem. Indus. v. Alphapharm Pty., Ltd., 492 F.3d 1350, 1356 (Fed. Cir. 2007).   In keeping with the flexible nature of the obviousness inquiry, KSR Int’l Co. v. Teleflex Inc., 127 S. Ct. 1727, 1739 (2007), the requisite motivation can come from any number of sources and need not necessarily be explicit in the art.  See Aventis Pharma Deutschland GmbH v. Lupin, Ltd., 499 F.3d 1293, 1301 (Fed. Cir. 2007).  Rather “it is sufficient to show that the claimed and prior art compounds possess a ‘sufficiently close relationship . . . to create an expectation,’ in light of the totality of the prior art, that the new compound will have ‘similar properties’ to the old.”  Id. (quoting Dillon, 919 F.2d at 692).

Teva tried to argue that a combination of three prior art references made the ’552 patent obvious: 1) European Patent No. 174,726, claiming lansoprazole (EP ’726); 2) United States Patent No. 4,255,431, claiming omeprazole (’431 patent); and 3) an article by Brändström, et al., entitled “Structure Activity Relationships of Substituted Benzimidazoles” (Brändström).

The court noted that omeprazole is structurally farther afield from rabeprazole than is lansoprazole and that rabeprazole, lansoprazole, and omeprazole are all Brändström core structure compounds.

In the end, the court found that potential solutions are less likely to be genuinely predictable in the chemical arts:

Under these assumptions, one of skill in this art may have considered [rabeprazole] a candidate for a lead compound in the search for anti-ulcer compounds.  To the contrary, the district court emphasized the differences between anti-ulcer action and gastric acid inhibition.  The trial court specifically noted that Teva’s expert testified with respect to the EP ’726 data that “[t]he level of acid secretion . . . from these [anti-ulcer] data . . . cannot be determined.”  SJ Validity Order at 13.  In this context, this court consults the counsel of KSR that “any need or problem known in the field of endeavor at the time of invention and addressed by the patent can provide a reason for combining the elements in the manner claimed.”  127 S. Ct. at 1742.  Thus lansoprazole’s candidacy as a starting point to develop new anti-ulcer compounds versus new gastric acid inhibitors does not resolve the lead compound analysis, at least not in the absence of any contrary indications.  Cf. Takeda, 492 F.3d at 1359 (negative side effects could dissuade one of skill from using a particular compound as a starting point).

In KSR, the Supreme Court noted that an invention may have been obvious “[w]hen there [was] . . . a design need or market pressure to solve a problem and there [were] . . . a finite number of identified, predictable solutions.” 127 S. Ct. at 1742 (tense changes supplied to clarify, as the Court stated and as per 35 U.S.C. § 103, that the obviousness inquiry must rely on evidence available “at the time” of the invention, see Takeda, 492 F.3d at 1356 n.2).  The Supreme Court’s analysis in KSR thus relies on several assumptions about the prior art landscape.  First, KSR assumes a starting reference point or points in the art, prior to the time of invention, from which a skilled artisan might identify a problem and pursue potential solutions.  Second, KSR presupposes that the record up to the time of invention would give some reasons, available within the knowledge of one of skill in the art, to make particular modifications to achieve the claimed compound.  See Takeda, 492 F.3d at 1357  (“Thus, in cases involving new chemical compounds, it remains necessary to identify some reason that would have led a chemist to modify a known compound in a particular manner to establish prima facie obviousness of a new claimed compound.”).  Third, the Supreme Court’s analysis in KSR presumes that the record before the time of invention would supply some reasons for narrowing the prior art universe to a “finite number of identified, predictable solutions,” 127 S. Ct. at 1742.  In Ortho-McNeil Pharmaceutical, Inc. v. Mylan Laboratories, Inc., 520 F.3d 1358, 1364 (Fed. Cir. 2008), this court further explained that this “easily traversed, small and finite number of alternatives . . . might support an inference of obviousness.”  To the extent an art is unpredictable, as the chemical arts often are, KSR’s focus on these “identified, predictable solutions” may present a difficult hurdle because potential solutions are less likely to be genuinely predictable.

In other words, post-KSR, a prima facie case of obviousness for a chemical compound still, in general, begins with the reasoned identification of a lead compound.  Teva cannot create a genuine issue of material fact on obviousness through the unsupported assertion that compounds other than lansoprazole might have served as lead compounds.  Further, the record contains no reasons a skilled artisan would have considered modification of lansoprazole by removing the lipophilicity-conferring fluorinated substituent as an identifiable, predictable solution.  In sum, the district court properly concluded that the record did not support a case of obviousness of the ’552 patent as a matter of law.

Posted July 24th, 2008 by Stephen Albainy-Jenei in Pharmaceutical, IP Litigation
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After vigorous debate, H.R. 6344 passed in the U.S. House of Representatives to amend 35 U.S.C. 156, the statute governing patent term extensions based on regulatory review delay.

This has been bounced around for several years now, and is intended (very specifically) to help Massachusetts-based The Medicines Company, which submitted its PTE application for U.S. Pat. No. 5,196,404 for ANGIOMAX (bivalirudin) 61 days after FDA approved its New Drug Application (NDA) .  In case you haven’t already guessed, the patent term extension law requires the submission within 60-days of the date of NDA approval.

Known as the “Dog Ate My Homework Act”, Section 4 of the bill involves a grant of authority to the Director or the United States Patent and Trademark Office (USPTO) to excuse specific late filings—this time, in connection with unintentional human error.  Section 4 would provide the USPTO with the authority to accept an application for patent term restoration under the Hatch-Waxman Act if that application is filed within three business days after the expiration of the 60-day period provided in subsection (d)(1) if the applicant files a petition, not later than five business days after the expiration of that 60-day period, showing, to the satisfaction of the Director, that the delay in filing the application was unintentional.

What’s most amazing is that the Act requires a payoff in order to effect a patent term extension — the patent holder must pay a fee to the United States Treasury equal to:

(i) $65,000,000 with respect to any original application for a patent term extension, filed with the United States Patent and Trademark Office before the date of the enactment of this Act, for a drug intended for use in humans that is in the anticoagulant class of drugs; or

(ii) the amount estimated under subparagraph (B) with respect to any other original application for a patent term extension.

Subparagraph (B) says the Director will estimate the amount required as the amount equal to the sum of:

(i) any net increase in direct spending arising from the extension of the patent term (including direct spending of the United States Patent and Trademark Office and any other department or agency of the Federal Government); (ii) any net decrease in revenues arising from such patent term extension; and (iii) any indirect reduction in revenues associated with payment of the fee under this subsection.

I supposed that $65M is not a bad deal for getting a patent extension depending on the patent.  The Medicines Co. wants its patent to be extended 1,773 days, giving it exclusive rights to the drug until Dec. 15, 2014.  Medicines expects Angiomax to generate more than $500 million in sales in the United States by 2010.

What a Diff’rence a Day Makes!

Posted June 26th, 2008 by Stephen Albainy-Jenei in Pharmaceutical, FDA, USPTO
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Generic drug maker Mylan got some good news from the U.S. Court of Appeals for the Federal Circuit in a patent litigation related to its heartburn treatment Omeprazole, the generic version of British drug maker AstraZeneca’s Prilosec, when the court affirmed a District Court ruling that Mylan’s 10 mg and 20 mg Omeprazole delayed-release capsules do not infringe AstraZeneca’s patents.  In re Omeprazole Patent Litigation (07-1476, -1477, -1478).

To say the least, AstraZeneca expressed disappointment with the ruling of noninfringement regarding it’s U.S. Patents 4,786,505 and 4,853,230.

Omeprazole is the generic name for Prilosec®. Omeprazole inhibits the production of gastric acid when, after absorption, Omeprazole transforms into its active species in the parietal cells (acid-producing cells in the stomach lining) and inhibits acid production. However, omeprazole degrades in acidic and neutral environments. Therefore, it must be protected from contact with gastric juices while traveling to the parietal cells. Thus, an omeprazole formulation needs a protective enteric coating around the core containing the active alkaline reacting compound (ARC) and a separating layer between that core and the coating.

Astra developed an oral dosage form of omeprazole that overcomes those formulation problems.  They developed an oral formulation that includes a core containing omeprazole and an alkaline reacting compound (ARC), a water soluble subcoat, and an enteric coating.

Astra brought suit against Mylan and Esteve, along with several other generic defendants, alleging infringement under the Hatch-Waxman Act.  Mylan’s products consist of (1) an inert sugar/starch sphere; (2) an active coating of omeprazole, talc, and hydroxypropyl methylcellulose (HPMC) (Film Coating No. 1 or active drug layer); (3) a subcoating of HPMC, talc, and titanium dioxide (Film Coating No. 2); (4) a second subcoating of HPMC and ethylcellulose (Film Coating No. 3); and (5) an enteric coating of methacrylic acid copolymer, triethylcitrate, and talc (the enteric coating).

The district court determined that Mylan/Esteve did not infringe either of the asserted patents and that Astra failed to show that Mylan/Esteve’s omeprazole products met the limitations of paragraph (a) of claim 1 of the patents in suit.  In particular, the court found that Astra failed to prove by a preponderance of the evidence that Mylan/Esteve’s products contained an ARC.  The court rejected Astra’s assertion that carbonates in either the talc or the HPMC, or the triethylamine in the omeprazole, satisfied the ARC and effective amount requirements of the asserted claims.

The issue on appeal was whether the district court erred in concluding that Astra failed to prove the presence of an ARC in Mylan’s products. In order to infringe the patents in suit, the accused products must contain an ARC in the active core region.  Previously, in Omeprazole I, the Federal Circuit had already affirmed the district court’s construction of an ARC, which was construed as:

(1) a pharmaceutically acceptable alkaline, or basic, substance having a pH greater than 7 that (2) stabilizes the omeprazole or other acid labile compound by (3) reacting to create a micro-pH of not less than 7 around the particles of omeprazole or other acid labile compound.

At trial, Astra argued that the talc used in the active drug layer of Mylan’s products, Microace® talc, was alkaline and that the source of alkalinity was carbonates.  More specifically, Astra argued that carbonates that are introduced into the active drug layer through the talc, and not the talc itself, are ARCs as that term is used in the patents in suit.

The district court considered and rejected Astra’s assertion.  The court primarily rested its conclusion on its finding that Astra failed to prove the presence of carbonates in Mylan’s products.  In doing so, the court considered the evidence proffered by both parties relating to the presence or absence of carbonates in the talc.

The court found that those tests indicated that Mylan’s talc contained no detectable amount of carbonates.  After weighing the competing evidence, the court found that Astra failed to prove the presence of carbonates in the talc of the accused products.  Since the determination is based on the district court’s fact findings, it cannot be overturned unless the Federal Circuit finds them to be clearly erroneous, and didn’t.

Astra argued that the district court was wrong to require conclusive evidence that carbonates were present in the talc, rather than preponderant evidence.  The Federal Circuit, however, pooh-pooh that idea saying the district court knew what it was doing.

See also:  Recognizing a Novel Characteristic After the Fact Doesn’t Make a Known Composition New Again

Posted June 12th, 2008 by Stephen Albainy-Jenei in Pharmaceutical, IP Litigation
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The U.S. Court of Appeals for the Federal Circuit looked at the issue of whether Aventis committed that most horrible of patent sins — inequitable conduct before the United States Patent and Trademark Office (PTO).   Aventis Pharma v. Amphastar and Teva (07-1280) .

Earlier, the CAFC held that the dosage of the prior art composition used in half-life comparisons with the patented composition was material to patentability but the court sent the case back to the district court to determine whether there was an intent to deceive by Aventis in failing to disclose the dosage.

The district court found that there was intent to deceive and held the patents unenforceable for inequitable conduct.  Because Aventis didn’t like that answer, the case went back before the CAFC.

Aventis appealed a District Court summary judgment in favor of Amphastar Pharmaceuticals and Teva Pharmaceuticals that held U.S. Pat. No. 5,389,618 and Reissue Patent No. 38,743 unenforceable. The ’618 patent and the ’743 reissue patent disclose and claim mixtures of low molecular weight herapin (“LMWH”) used to prevent blood clots and sold as Lovenox® (enoxaparin sodium injection).

Initially, the patent examiner rejected the claims over several references, including European Patent 40,144, stating that each of the prior art references teaches sulfated heparinic admixtures within the molecular weight range of the claims and is considered to be inherently the same as the claimed admixtures.

In response, Aventis argued that EP ’144 does not expressly state that the mixture contains two types of polysaccharides, one with a MW less than 2,000 daltons and one with a MW greater than 8,000 daltons, nor does it state the number average/weight average MW ratio.  Aventis also argued that the evidence in the specification rebuts inherency.

Based on methods of Example 6 by Dr. Uzan, Aventis argued that the claimed LMWHs exhibit a significantly longer half-life than formulations prepared in accordance with EP ’144.  Aventis went on to explain that, because it is well established that compounds are inseparable from their properties, the evidence of a difference in a property, i.e., half-life, serves as evidence of a difference in structure.

The examiner also reiterated that the Patent and Trademark Office does not have facilities for testing and comparing various products, and where the prior art teaches a product which is identical or nearly identical to that claimed, it is incumbent upon the Applicant to convincingly demonstrate that the claimed product provides some unexpected or unobvious property not demonstrated by the prior art products.

In a first declaration, Dr. Uzan distinguished the claimed formulations from the formulations in EP ’144 and concluded that “the formulations of [EP ’144] are clearly outside the scope of the present invention.” In a second declaration, Dr. Uzan referenced five tables comprising the raw data from the half-life comparisons between the claimed compound and the EP ’144 compound, which tables were attached to the declaration.  The mean half-life for the EP ’144 compound was taken from Table III, which did not mention the dosage.

On appeal, Aventis argued that the district court erred in finding materiality because if the dose information were material to patentability, the examiner would have requested it because: she was presented with half-life data that enabled her to compare various doses, Dr. Uzan informed the examiner that the half-life comparison was done at different doses, those of skill in the art frequently compare half-lives at different doses, and half-life is independent of dose.

The district court determined that the representation by Aventis that the patented compound had an improved half-life as compared to the EP ’144 compound was material to patentability because Aventis referred to the improved half-life at least four times during prosecution and the examiner ultimately allowed the ’618 patent application after the final representation that the difference in mean half-life was statistically significant.  The court found a strong inference of intent to deceive because it could find no credible explanation for comparing half-lives at different doses and because comparisons at the same dose showed little difference in half-life.

On the second go-around up the appeal food chain, Aventis argued that the district court made two clearly erroneous findings of fact: (1) that the central question relating to patentability was compositional differences, and (2) that the purpose of Dr. Uzan’s half-life comparisons was to show compositional differences.

Aventis offered a new reasonsfor Dr. Uzan’s failure to disclose the dosage information in his half-life comparisons.  According to Aventis, Dr. Uzan’s half-life comparisons were intended to show a difference in properties in response to the obviousness rejection under 35 U.S.C. § 103, not to demonstrate a compositional difference to address the anticipation rejection under 35 U.S.C. § 102, as the district court concluded.

The CAFC was totally unmoved by this stating:

We find nothing in the district court’s opinion to suggest that it did not recognize the existence of the obviousness rejection, or that it believed the anticipation rejection to be the only rejection of record.  Indeed, several statements in the opinion clearly indicate that the court was aware of the obviousness rejection.

Aventis also tried arguing that the district court made a mistake in excluding evidence that comparison of half-lives at different doses (the “clinically relevant dose”) was the standard practice in the LMWH field.  This was also a no-go:

We find no abuse of discretion by the court’s exclusion of the evidence.  First, evidence of industry practice of clinically-relevant doses would only be pertinent if there was a finding that the half-life comparisons were used to address obviousness, and not anticipation, because Aventis has conceded that half-life comparisons must be at the same dose to show compositional differences.  Here, however, the district court found, and we have affirmed, that the half-life comparisons were at least in part intended to show compositional differences to address the anticipation rejection.

Furthermore, the district court, after examining all of the evidence, found it simply incredible that Dr. Uzan selected the clinically relevant doses for his half-life comparisons.

Aventis tried several additional arguments focused on whether Dr. Uzan really had deceptive intent but the court just yawned through those and affirmed the lower court.

Judge Rader, dissenting, felt that the law should limit a finding of inequitable conduct (as he calls the “atomic bomb” remedy of unenforceability) to only the most extreme cases of fraud and deception:

In Kingsdown, this court clearly conveyed that the inequitable conduct was not a remedy for every mistake, blunder, or fault in the patent procurement process.  Even mistakes that struck at the heart and integrity of the process—like repeatedly recopying and acquiring rights to a rejected claim—did not amount to inequitable conduct.  Instead this court required “culpable” conduct supported by clear and convincing evidence of intent to deceive the USPTO.  Halliburton Co. v. Schlumberger Tech. Corp., 925 F.2d 1435, 1443 (Fed. Cir. 1991) (citing Consol. Aluminum Corp. v. Foseco Int’l Ltd., 910 F.2d 804, 809 (Fed. Cir. 1990)).  At the same time, it is hard to imagine a more material mistake than reasserting claims to rejected subject matter.  Materiality of any undisclosed or misleading information, of course, is the other prong of an inequitable conduct analysis.  Cargill, Inc. v. Canbra Foods, Ltd., 476 F.3d 1359, 1363 (Fed. Cir. 2007).  In sum, Kingsdown properly made inequitable conduct a rare occurrence.

Posted June 9th, 2008 by Stephen Albainy-Jenei in Pharmaceutical, IP Litigation
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Biovail Corp., Canada’s largest publicly traded drugmaker, announced that it has settled with the United States Department of Justice (DOJ) regarding criminal allegations related to activities surrounding the 2003 commercial launch of Cardizem LA. The DOJ alleges that prior management’s actions in 2002 and 2003 in respect of the Cardizem LA clinical experience program, titled PLACE (Proving L.A. through Clinical Experience).

Cardizem LA (diltiazem) is a long-acting drug and part of a group of drugs called calcium channel blockers, which work by relaxing the muscles of your heart and blood vessels. Diltiazem is used to treat hypertension (high blood pressure), angina (chest pain), and certain heart rhythm disorders. In 2003, an administrative inquiry reported that Biovail planned to offer doctors $1,000 to write 15 prescriptions for Cardizem LA, then complete a report on each patient.

Under the terms of the agreement, Biovail Pharmaceuticals, Inc. (BPI), would plead guilty to charges relating to making payments to induce purchasing or ordering of Cardizem(R) LA in 2003 and would pay $24.6 million to fully settle this matter.  As part of the agreement, Biovail expects to get full releases for all matters related to the DOJ’s investigation.

The agreement eliminates any criminal liability for Biovail Corporation arising from this matter, and preserves the Company’s ability to conduct business in the United States. Without this agreement, the Company was at risk of being excluded from doing business with any health program sponsored by the U.S. federal government. The agreement is subject to approval at a court hearing.

Cardizem LA had $10.2 million in revenue in the first quarter, down 57 percent from $23.9 million a year earlier. In December, the company agreed to pay $138 million to settle a securities fraud class-action suit brought by investors who claimed the company’s officers and directors lied about the effectiveness of Cardizem LA when it was introduced in 2003.

This comes as many groups are starting to ban give aways to doctors. Earlier, Vanderbilt Medical Center and Stanford joined other institutions in banning gifts, meals and toys from drug reps as part of a new conflict of interest policy. The policy, to be phased in by July 1, will also preclude most employees from accepting free meals.

See more about Biovail’s previous administration under former Chairman and CEO Eugene Melnyk where the Securities and Exchange Commission charged the corporation and its former CEO, former CFO, and two current senior executives with engaging in a number of fraudulent accounting schemes and making a series of misstatements to analysts and investors.  (see complaint here)

See also: NIH Scientist Could Get Prison and $100K Fine

Posted May 19th, 2008 by Stephen Albainy-Jenei in Conflicts of Interest, DOJ, Pharmaceutical
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What happens when a brand name drug company asserts that a patent covers its drug and then pulls it out from the Orange Book? You fight to get it back in, that’s what.

In August, Teva Pharmaceuticals USA submitted a Citizen Petition pursuant to section 505 of the Food, Drug, and Cosmetic Act (FDCA) asking the FDA to do just that.

The FDA’s official Approved Drug Products with Therapeutic Equivalence Evaluations (the “Orange Book“) listed two patents as claiming Risperdal® tablets: U.S. Patent No. 4,804,663, which was set to expire on December 29, 2007, and U.S. Patent No. 5,158,952 (”the ‘952 patent”), which will expire on October 27, 2009.  Risperidone is an antipsychotic medication sold by Janssen Pharmaceutica (a subsidiary of Johnson & Johnson) under the trade-name Risperdal®.

Teva submitted an original Abbreviated New Drug Application (ANDA) seeking approval to market generic risperidone tablets. Because the Orange Book listed both the ‘663 and ‘952 patents for Risperdal® tablets, Teva was required to certify as to both patents.

Teva filed a certification under § 355(j)(2)(A)(vii)(III) (”Paragraph III certification”) as to the ‘663 patent, which is set to expire on December 29, 2007, and a certification under § 355(j)(2)(A)(vii)(IV) (”Paragraph IV certification”) as to the ‘952 patent, asserting that the patent was invalid or would not be infringed by Teva’s generic risperidone tablets.

Ordinarily, Teva would be entitled to 180 days of marketing exclusivity for its generic risperidone tablets as a result of its paragraph IV certification to the ‘952 patent. That’s because the ‘952 patent appeared in the official Orange Book when it originally filed – that meant that Teva was required to submit a certification to that patent at the time it submitted its ANDA for generic risperidone drug products. Teva then became the first company to submit a paragraph IV certification to any of the listed patents claiming Risperdal®.

On October 12, 2001, FDA notified Teva that it had “delisted” the ‘952 patent from the Orange Book (even though it continued to appear in the official Orange Book at that time) It also informed Teva that it would not accept Teva’s ANDA for filing unless Teva modified its patent certification to reflect that the ‘952 patent was no longer listed as claiming the reference drug product.

In November 2006, the D.C. Circuit ruled that the plain text of the FDCA prevented the FDA from effectuating the delisting of a patent following the submission of a paragraph IV certification as to that patent. Ranbaxy Laboratories Ltd. v. Leavitt, 469 F.3d 120, 125-26 (D.C. Cir. 2006). The court struck down the FDA’s practice because it “changed the incentive structure adopted by Congress,” by “depriving the generic applicant of a period of marketing exclusivity” after the generic manufacturer had expended significant resources in developing a non-infringing generic substitute and undertaken the risk of infringing the patent by filing a paragraph IV certification.

Teva then filed a Citizen’s Petition with the FDA arguing that the FDCA entitles Teva to a 180-day period of first-filer exclusivity for generic Risperdal® tablets since it was the first generic manufacturer to file an ANDA for generic risperidone tablets containing a paragraph IV certification as to the ‘952 patent.

Under 21 U.S.C. § 355(j)(5)(B)(iv) (2002), the earliest any subsequently-filed paragraph IV ANDA can be approved is “one hundred and eighty days after” Teva first commercially markets its generic risperidone tablets or the date of a court decision holding the ‘952 patent to be invalid or not infringed.

Teva argued that both FDA regulations and case law make clear that the agency does not adjudicate questions of patent law; instead, it plays only a ministerial role in maintaining the Orange Book. As a result, where a patent remains listed for a particular drug in the official Orange Book, a generic applicant has no choice but to believe that the NDA holder is continuing to assert that patent as claiming the listed drug.

Thus, at the time of its ANDA submission in August 2001, Teva was required to submit a certification to the ‘952 patent. Teva now wants its 180-exclusivity for these drug products.

The question here is whether or not a brand manufacturer can game the system by delisting a patent after the submission of a paragraph IV certification and without notice, forcing generic manufacturers to invest resources and assume the risk of patent litigation without any guarantee of the 180-day exclusivity reward.

The FDA wrote back a nice note to Teva:

We have carefully reviewed your Petition and have concluded that the ‘952 patent was delisted before Teva submitted ANDA 76-228 to FDA. For the reasons described in further detail in this Response, we deny your request that FDA relist the ‘952 patent. As Teva’s ANDA did not contain a paragraph IV certification for a listed patent, and Teva did not provide the required notice of such certification to the holder of the NDA for the reference listed drug and each owner of the listed patent, Teva would not be eligible for 180-day exclusivity pursuant to section 505(j)(5)(B)(iv) of the Act for its pending ANDA 76-228.

Like a game of Calvinball*, since the FDA had itself forced Teva to remove the paragraph IV certification or it wouldn’t accept the ANDA, the FDA now claims that Teva’s out of luck because it did, in fact, take out the certification.

Nice.

It probably wouldn’t take a law degree to guess that Teva has filed a lawsuit in federal court to try to get the Petition granted. Johnson & Johnson’s sales of antipsychotics in the U.S. were more than $2.7 billion last year with Risperdal accounting for a large part of that amount. A generic can make quite a bit in just 180 days.

Stay tuned.

Teva vs. FDA Complaint

[*Note: Under the Official Rules of Calvinball, Rule 1.2. states: “Any player may declare a new rule at any point in the game (Figure 1.2). The player may do this audibly or silently depending on what zone (Refer to Rule 1.5) the player is in.”]

Posted March 7th, 2008 by Stephen Albainy-Jenei in Pharmaceutical, Generic drugs, FDA, IP Litigation
| | 3 Comments »

At the beginning of the last century, the majority of drug products available were ineffective for their stated purpose at best and worsened the conditions they were purported to cure at worse.  For many of these so-called Patent Medicines, the main active ingredient was a form of alcohol (in the case of the Toneco Bitters bottle above, 30% according the lower label).

Note:  Few if any of the elixers were actually patented — these were medicines with trademarks, not patented medicines.  The phrase patent medicine comes from the late 17th century marketing of medical elixirs, when some were issued letters patent authorizing use of a royal endorsement in advertising.

A series of articles in Collier’s magazine, published in 1905-06, began with these words:

Gullible America will spend this year some seventy-five millions of dollars in the purchase of patent medicines.  In consideration of this sum it will swallow huge quantities of alcohol, an appalling amount of opiates and narcotics, a wide assortment of varied drugs ranging from powerful and dangerous heart depressants to insidious liver stimulants; and, far in excess of all other ingredients, undiluted fraud.

Samuel Hopkins Adams, The Great American Fraud 36 COLLIER’S 14 (Oct. 7, 1905).

This series of articles contributed to the pressures to enact laws regulating the food and drug industries, ultimately resulting in the Federal Food, Drug, and Cosmetics Act (FD&C Act).

Since 1962, before a new drug can be marketed in the US, the Food and Drug Administration (FDA) must approve it, after it is shown to be safe and effective. This has not been without side-effects since the FDA requirement that a new drug is safe and effective, which ordinarily means that a company must complete clinical trials, which increased the cost of developing new drugs and delays their introduction.

According to conventional wisdom, the cost and delay involved in this process lessens incentives to invest in the development of new drugs.  Accordingly, several reforms aimed at restoring such incentives have been implemented and many others have been advocated.

One way that drug companies are compensated for the regulatory burden is the extension of patent terms. In the US, the Drug Price Competition and Patent Term Restoration Act of 1984 (Hatch-Waxman Act) makes it possible for drug patentees to have the term of their patent extended for as much as five years if they meet certain criteria.  In the EU, there is the Supplementary Protection Certificate (SPC).

Ariel Katz, Assistant Professor at the University of Toronto, has now published a paper looking at some of the effects of regulation in the drug industry entitled “Pharmaceutical Lemons: Innovation And Regulation In The Drug Industry.”

This paper looks at the argument that drug regulation and drug innovation are at odds with each other and shows that the regulatory framework is not solely a burden imposed on the industry; it also provides a valuable service to the industry, that is, drug regulation provides certification of drug quality.  This certification contributes to the value of new drugs and may actually encourage innovation.

Prof. Katz now challenges the argument that new drug regulation negatively affects the incentives for new drug innovation. It’s good food for thought on the ripple effects of drug regulations.

This paper, published in 14 Michigan Telecommunications and Technology Law Review, can be downloaded without charge at the Social Science Research Network Electronic Paper Collection.

[Side note:  Some consumer products were once marketed as patent medicines but have been reformulated and are no longer sold for medicinal purposes. Their original ingredients may have been changed to remove drugs, such is the case with Coca-Cola®.  Others, like Vicks VapoRub® still exist.]

Posted March 4th, 2008 by Stephen Albainy-Jenei in Pharmaceutical, FDA
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Kurt Karst of the FDA Law Blog ran a nice update on patent term extension (PTE) legislation. The legislation, known as the “Dog Ate My Homework Act,” would permit the U.S. Patent and Trademark Office to exercise discretion to accept untimely filed Patent Term Extension (PTE) applications has been added to the Patent Reform Act of 2007 (S. 1145) by Senator Edward Kennedy (D-MA).

Representative William Delahunt (D-MA), who introduced a stand-alone bill earlier this year in the House, H.R. 1778, is trying to get the legislation added to the House version of the Patent Reform Act of 2007” (H.R. 1908).

This has been bounced around for several years now, and is intended (very specifically) to help Massachusetts-based The Medicines Company, which submitted its PTE application for U.S. Pat. No. 5,196,404 for ANGIOMAX (bivalirudin) 61 days after FDA approved its New Drug Application (NDA) .

In case you haven’t already guessed, the patent term extension law requires the submission within 60-days of the date of NDA approval. You can just hear the “Doh!”

A copy of Sen. Kennedy’s amendment agreed to at the Senate Judiciary Committee Executive Business Meeting is available here.

What a Diff’rence a Day Makes!

Posted August 8th, 2007 by Stephen Albainy-Jenei in Pharmaceutical, Patent Reform, FDA, USPTO
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