Patent Baristas

The European Union decided against allowing a protein drug derived from the milk of genetically-engineered goats. In a press release, the European Medicines Agency (EMEA) in London said it had rejected the application to license a natural human protein extracted from the milk of goats. EMEA recommended against approval of ATryn (recombinant antithrombin alpha), which was set to become the world’s first medicine to be produced from a genetically modified animal. The 57 unique goats that produced the drug-laden milk live on a farm belonging to GTC Biotherapeutics.

The Committee for Medicinal Products for Human Use (CHMP) adopted a negative opinion, refusing to allow the marketing authorization for ATryn 1750 IU powder for solution for infusion, to be used in surgical patients with congenital antithrombin deficiency for the prophylaxis of deep vein thrombosis and thromboembolism in clinical risk situations, i.e., during the peri-surgical period. Genzyme Europe B.V. may request a re-examination of the opinion.

ATryn was to be used in patients who have an inherited reduction of the protein antithrombin, to prevent problems due to the formation of clots in the vessels of the legs (deep vein thrombosis, DVT) or in other vessels of the body (thromboembolism) during high risk situations (for example major surgery). ATryn is an anti-clotting agent. The active substance in ATryn, antithrombin alpha, is a copy of the natural blood protein that is produced by recombinant DNA technology. It is extracted from the milk of goats who have a gene (DNA) inserted, which make them able to produce the human protein in their milk.

In the body, antithrombin blocks thrombin, one of the substances involved in blood coagulation (clotting). Thrombin plays a central role in the process of blood clotting. Patients who have a congenital antithrombin deficiency have blood levels of antithrombin that are lower than normal, which may result in a reduced anti-clotting capacity of the blood. This increases the risk of the formation of clots during high-risk situations. ATryn would be expected to correct the antithrombin deficiency and to give temporary control of the clotting disorder.

The disease is rare (it is estimated that about one person in 3, 000 to 5,000 have a congenital antithrombin deficiency), and this explains why few patients have been treated during the studies. However, for the proposed indication, only 5 surgical cases were considered. The CHMP considered this number to be too small, and not in line with the EMEA’s recommendation of 12 patients.

The results in patients treated in the compassionate use program and at childbirth could not be used to support the proposed use in patients undergoing surgery. Also, the process for the production of the medicine used in the studies is not exactly the same as that which would have been marketed (addition of a filtration step). ATryn is a protein-based medicine, and, like all protein-based medicines, it is possible that patients develop antibodies (proteins produced in response to ATryn). The CHMP considered that they did not carry out enough studies looking for the development of antibodies.

At this point in time, the CHMP was of the opinion that it was not yet demonstrated that ATryn’s benefits are greater than its risks. Hence, the CHMP recommended that ATryn be refused authorization in the EU. Progress has been slow in bringing products to market that are derived from animals. It has been nearly 14 years since the birth of GTC’s first ATryn goat, and not a single product has made it to market yet.

See the EMEA Opinion here.

On January 17, 2006 Judge Rodney Sippel of the U.S. District Court for the eastern district of Missouri has ruled under summary judgment in favor of the generic challengers, clearing their way to launch generic versions of Toprol-XL in U.S. market. This is, however, a pyrrhic victory for generic manufactures after successive para IV defeats in Lipitor (Atorvastatin Calcium, Ranbaxy losing to Pfizer), Accupril (Quinapril Hydrochloride, Ranbaxy losing to Pfizer), Norvasc (Amlodipine Besylate, Dr. Reddy’s loses to Pfizer) and Zyprexa (Olanzapine, Dr. Reddy’s loses Eli Lilly). The court has favored suits filed by KV Pharmaceutical Co, Andrx Corp. and Eon Labs Inc. (a unit of Novartis AG), challenging the validity and enforceability of Orange Book listed patents. Astra, which earlier contended before the District Court that its patents on Toprol-XL will survive their patent term, has now announced their intention to appeal against the judgment in the U.S. Court of Appeals for the Federal Circuit maintaining that both US patents (5001161 and 5081154) are valid and enforceable.

Another Para IV Patent Litigation

To recap, in February 2004, AstraZeneca filed a patent infringement lawsuit against Andrx Corp. in the United States District Court for the District of Delaware as a result of a Paragraph IV certification letter submitted by Andrx concerning its intent to manufacture and sell generic form of Toprol-XL in the 50 mg dose form in US. Again, in July 2004 AstraZeneca filed a second patent infringement against Andrx Corp. in the same District Court following the Andrx’s notification that it had filed ANDA under paragraph IV with USFDA for seeking approval to market generic form of Toprol-XL 50 mg dose form. Astra advocated that Andrx infringes its patents covering Toprol-XL.

In the same year, AstraZeneca also filed a lawsuit in the District Court for the District of Delaware against generic manufacture, Eon Labs, for patent infringement following the Eon’s move for market approval of generic form of Toprol-XL for all dose forms under paragraph IV.

Moreover, later in the same year, AstraZeneca filed legal proceedings against KV Pharmaceutical Co. in the District Court for the Eastern District of Missouri this time following the KV’s notification regarding ANDA submission under paragraph IV for market approval of generic form of Toprol-XL 50 mg dose form. Earlier to this AstraZeneca filed a suit in May 2003 against KV Pharmaceutical Co. for patent infringement by the 200mg dose form of Toprol-XL and again in August 2003 for patent infringement by the 100 mg dose form.

Pre-trial Discovery

All of these pending patent litigations later consolidated for pre-trial discovery purposes and motion practice in the U.S. District Court for the Eastern District of Missouri, which do not include a jury. A pre-trial discovery means that a party to a lawsuit should not be surprised by its adversary on the day of trial, and therefore has the right to full discovery, prior to trial, of all relevant evidence, including documents (broadly defined to include virtually every tangible and intangible form of record keeping) and witness testimony related to the matter at issue in the litigation. In other words, each party to the suit attempts to “discover” relevant or pertinent facts. However, in this trial consideration was of the validity and enforceability of two AstraZeneca patents (US Patent No. 5,081,154 and 5,001,161) relating to active ingredient (metoprolol succinate per se) and composition of Toprol-XL (extended release tablet of metoprolol succinate) and to determine whether the defendants in the case infringe those patents. Both ‘154 and ‘161 patent were due to expire in September of 2007.

Astra’s Setback, Generics Roller Coaster!

The judgment day belongs to generics, a much needed victory for all Para IV seekers. Judge Rodney Sippel in his summary judgment found that AstraZeneca’s patents (US Patent No. 5,081,154 and 5,001,161) on Toprol-XL were “both invalid due to double patenting and are unenforceable due to inequitable conduct.” Astra’s both ‘161 patent and ‘154 patent are invalidated on the basis of double patenting over the US 4,780,318 patent and are considered unenforceable based on Astra’s inequitable conduct in the prosecution of these patents in the United States Patent & Trademark Office concerning inventorship dispute over metoprolol succinate with their competitor named Lejus Medical. However, it was also argued during proceedings that Astra intentionally did not name the correct inventors in Astra’s prosecution of patents in suit. Court found that Astra’s failure was done with an intent to deceive the patent examiner about the inventorship dispute and to avoid questions concerning Astra’s ability to claim priority to the ‘318 patent application and to avoid potential prior art concerning metoprolol succinate.

This means that now generic challengers can launch their generic copies of Toprol-XL in US. Andrx being the first to file ANDA under Para IV will be, however, entitled to 180-days exclusivity on the 50mg strength of generic Toprol-XL under Hatch-Waxman Act. But Andrx’s approval and launch of generic Toprol-XL will depend on FDA clearance and approval requirements and potential future legal proceedings by AstraZeneca, which is likely to happen. Even though, Astra is proposing to appeal the against the judgment in the U.S. Court of Appeals for the Federal Circuit, what cannot be denied is the major setback faced by Astra, particularly when its two other top selling drugs – antiulcerant Nexium (challenged by Ranbaxy) and schizophrenia drug Seroquel (challenged by Teva) are also subject of pending Para IV Patent Litigation.

Today’s post comes from Varun Chhonkar, Senior Officer – Patents with J.B. Chemicals & Pharmaceuticals Ltd., Mumbai, India (varun.chhonkar[at]jbcpl.com). © Varun Chhonkar.

The Supreme Court agreed to consider allowing a lawsuit by MedImmune Inc. that seeks to end royalties the company pays on its drug Synagis to go forward. The Court agreed to review a Federal Circuit decision that a licensee may not use a declaratory judgment action to challenge the validity of the licensed patent where the licensee is paying royalties and observing the terms of the patent license agreement.

The Federal Circuit ruling rejected the view that licensee rights established under Lear v. Atkins, 395 U.S. 653 (1969), permit the validity challenge, stating that this case is governed not by the bar against licensee estoppel, but by the Constitution’s requirement of a case or controversy.

MedImmune, Inc., a licensee of a patent owned by Genentech, Inc., sought a declaratory action to challenge the validity and enforceability of the licensed patent on various grounds flowing from the settlement of a patent interference between Genentech and Celltech R&D, Ltd. The U.S. District Court held that because MedImmune continues to comply fully with the license terms, leaving no possibility of infringement suit or license cancellation by Genentech, there is no “case of actual controversy” as required by the Declaratory Judgment Act, 28 U.S.C. §2201. The district court also dismissed MedImmune’s antitrust and unfair competition counts claiming that Genentech illegally obtained a patent on an antibody synthesis technology used in the production of Synagis, a MedImmune drug that prevents certain respiratory infections in babies.

The U.S. Court of Appeals for the Federal Circuit affirmed (See MedImmune Inc. v. Genentech, 04-1300, -1384) holding that:

The settlement of disputes such as priority in patent interferences is not a presumptive violation of antitrust law; such violation requires a showing of market power and other antitrust predicates. A patent does not of itself confer market power or a presumption thereof for purposes of the antitrust laws. See C.R. Bard, Inc. v. M3 Sys., Inc., 157 F.3d 1340, 1368 (Fed. Cir. 1998) (“It is not presumed that the patent-based right to exclude necessarily establishes market power in antitrust terms.”); Abbott Labs., 952 F.2d at 1354 (Fed. Cir. 1991) (“A patent does not of itself establish a presumption of market power in the antitrust sense.”); American Hoist & Derrick Co. v. Sowa & Sons, Inc., 725 F.2d 1350, 1367 (Fed. Cir. 1984) (“patent rights are not legal monopolies in the antitrust sense of the word”); Jefferson Parish Hosp. Dist. No. 2 v. Hyde, 466 U.S. 2, 18 (1984) (“any inquiry into the validity of a tying arrangement must focus on the market or markets in which the two products are sold, for that is where the anticompetitive forcing has its impact”); In re Independent Service Organizations Antitrust Litigation, 203 F.3d 1322, 1329 (Fed. Cir. 2000) (“patent alone does not demonstrate market power”); Independent Ink, Inc. v. Illinois Tool Works, Inc. 396 F.3d 1342, 1348 (Fed. Cir. 2003) (“the Supreme Court has held that there is a presumption of market power in patent tying cases”), cert. granted, 125 S. Ct. 2937 (June 20, 2005); Herbert Hovenkamp, Federal Antitrust Policy: The Law of Competition and its Practice §10.3 (3d ed. 2005) (“most patents confer absolutely no market power on their owners”).

MedImmune claims that Genentech violated antitrust law by colluding with Celltech in obtaining an extension on the antibody production patent, and MedImmune is seeking to have Genentech’s patent declared invalid.

The U.S. Patent and Trademark Office is also reviewing Genentech’s Cabilly patent under concurrent proceedings for an Inter Partes Reexamination (RE Appl. No. 90/007,542) and an Ex Parte Reexamination (RE Appl. No. 90/007,859). In an earlier ruling, the U.S. Patent and Trademark Office (USPTO) issued an obviousness-type double-patenting rejection and a “Schneller-type” double patenting rejection on the Genentech patent indicating that the patent, awarded in 2001, covered basically the same invention as an earlier Genentech patent that was set to expire next March.

For background, on March 25, 1983, Celltech filed in the United Kingdom a patent application directed to methods of making recombinant antibodies and antibody fragments, together with vectors and host cells useful in these processes. Celltech filed a related patent application in the United States, which issued as U.S. Patent No. 4,816,397 (“the Boss Patent”). On April 8, 1983, about two weeks after Celltech’s original U.K. filing, Genentech filed a United States patent application directed to similar technology, which issued as U.S. Patent No. 4,816,567 (“the Cabilly Patent”). The Boss Patent and the Cabilly Patent issued on the same day, and both were scheduled to expire on March 28, 2006.

The USPTO ultimately revoked the Boss Patent and issued a new United States patent, U.S. Patent No. 6,331,415 to Genentech (“the New Cabilly Patent”). All the claims originally issued in the revoked Boss Patent subsequently issued in the New Cabilly Patent. As a result, while the disputed invention was originally scheduled to pass into the public domain in 2006 upon expiration of the Boss Patent, it is now owned exclusively by Genentech until 2018, which is when the New Cabilly Patent is scheduled to expire.

MedImmune is now claiming that Genentech and Celltech conspired improperly to secure for themselves, through 2018, a dominant and exclusive position in the recombinant antibody field. As we’ve said before, it’s too early to try to predict the outcome so it is not clear yet if companies developing recombinant antibody-based products will become free and clear of the Boss Patent and the Cabilly Patent in 2006.

In Ferring B.V., and Aventis v. Barr Labs, (05-1284), the Court of Appeals for the Federal Circuit, deemed a patent unenforceable due to inequitable conduct where the inventors submitted declarations to the examiner in order to define the term “peroral” but did not disclose to the examiner that some of the declarants had been employed by the applicant’s company or performing paid research for the company.

Ferring B.V. and Aventis Pharmaceuticals sued Barr Laboratories for infringement of Ferring’s patent, U.S. Patent No. 5,047,398 (‘398 patent). The ‘398 patent claimed an “antidiuretic composition for humans comprising a gastrointestinally absorbable, antidiuretically effective, amount of [the peptide] 1-deamino-8-D-arginine vasopressin and a pharmaceutically acceptable carrier in solid oral dosage form for absorption in the gastrointestinal tract of said humans.”

Desmopressin acetate (DDAVP) is approved as anti-diuretic replacement therapy in the management of central diabetes insipidus and to manage the temporary polyuria and polydipsia following head trauma or surgery in the pituitary region. It is also approved for the management of primary nocturnal enuresis.

1-deamino-8-D-arginine vasopressin and other compounds were known in the art to prevent the diuretic symptoms associated with diabetes when they were absorbed through the walls of the patient’s mouth via a dissolving tablet, or through the patient’s nasal passage via a liquid spray or plastic tube. However, such modes of administering the medicine proved cumbersome and time-consuming. Therefore, the claimed solid oral dosage form of the compound and method of administering it were thought to be an improvement over the prior art, because the medicine was designed to be simply swallowed and absorbed through the gastrointestinal tract.

During prosecution, the examiners discussed certain prior art references, including U.S. Patent No. 3,497,491, which taught, for antidiuretic purposes, that “1-deamino-8-D-arginine vasopressin” “may be used . . . for the parenteral, peroral, intranasal, subcutaneous, intramuscular, or intravenous application.”

The examiners were concerned that the ‘491 patent’s disclosure of the “peroral” application of the peptide may have suggested the oral administration of the peptide for gastrointestinal absorption. Vilhardt argued that the term “peroral” as used in the ‘491 patent did not teach the oral administration of the peptide for gastrointestinal absorption, but rather for absorption through the walls of the mouth. As the examiners were not entirely convinced, they “suggested that applicants obtain evidence from a non-inventor” to support their interpretation of the term “peroral.”

The inventors submitted declarations explaining the scientific belief that the term “peroral” in the ‘491 patent meant that the compound could be administered “through the mouth,” but only for absorption through the cheek of the mouth or under the tongue. However, the declarations failed to disclose that a declarant had been receiving research funding from Ferring from to conduct a clinical investigation relating to a particular drug (DDAVP) preparation (although he testified that he was not receiving funding from Ferring in June 1986, when he submitted his first declaration). They also failed to inform the examiners that one of the new declarants had been Ferring’s pre-clinical research director and a paid consultant for Ferring.

In the end, four of the five declarations submitted to the PTO in 1990 were written by scientists who had been employed or had received research funds from Ferring, and Vilhardt participated in the drafting of two of the four declarations submitted by non-inventors. The examiners were not otherwise made aware of the Ferring connections and allowed the previously rejected claims.

The district court granted summary judgment to Barr on grounds of inequitable conduct, stating:

The undisputed evidence in this case supports the finding of inequitable conduct by the patentee and its agents and the grant of summary judgment. The reluctance of the PTO to issue the ‘398 patent was evident. Each affidavit submitted in support of its issuance was thus highly material to the prosecution history. That three of the challenged declarations were submitted after several iterations of rejected attempts to obtain the patent’s issuance speaks loudly as to motive and intent. While credibility determinations from a courtroom observation may at times be necessary on the issue of intent, here, the entire record presents clear and convincing evidence of an intent to mislead the examiners, even viewing the evidence, as it must be viewed, in the light most favorable to Plaintiff.

Inequitable conduct occurs when a patentee breaches his or her duty to the PTO of ‘candor, good faith, and honesty. While inequitable conduct includes affirmative misrepresentations of material facts, it also arises when the patentee fails to disclose material information to the PTO. The inequitable conduct analysis is performed in two steps comprising first, a determination of whether the withheld reference meets a threshold level of materiality and intent to mislead, and second, a weighing of the materiality and intent in light of all the circumstances to determine whether the applicant’s conduct is so culpable that the patent should be held unenforceable. The predicate facts must be proven by clear and convincing evidence.

On appeal, they argue that the Ferring affiliations were immaterial as a matter of law because (1) those affiliations supposedly did not bear directly on the critical assertion that each made in his declaration, meaning that the relationships were not the source of the information in the declarations, and (2) the declarants did not have a direct financial stake in the success of the patent.

The CAFC saw it differently:

Our jurisprudence does not suggest such a narrow view of materiality. A witness’s interest is always pertinent to his credibility and to the weight to be given to his testimony, and relevant interests are not limited to direct financial interests. Under Refac and Paragon, a declarant’s past relationships with the applicant are material if (1) the declarant’s views on the underlying issue are material and (2) the past relationship to the applicant was a significant one. Here we think that each of these requirements was satisfied on the summary judgment record.

The CAFC felt that the affirmative act of submitting an affidavit must be construed as being intended to be relied upon and that it is not comparable to omitting an unnecessary act. The court stated that these relationships were not isolated, nor were they confined to the distant past. The declarants clearly had ongoing and mutually beneficial relationships with Ferring during the prosecution of the ‘398 patent:

Even if an omission is found to be material, the omission must also be found to have been made with the intent to deceive. In the absence of a credible explanation, intent to deceive is generally inferred from the facts and circumstances surrounding a knowing failure to disclose material information. Thee question of intent is directed to the applicant’s intent, not to the intent of the declarants. Thus, that the declarants may have had no intent to deceive is entirely irrelevant. The question is whether the applicant (here Vilhardt) had such an intent.

We need not in this case attempt to lay down a general rule as to when intent may be or must be inferred from the withholding of material information by an applicant. Suffice it to say that we have recognized, in cases such as Paragon, that summary judgment is appropriate on the issue of intent if there has been a failure to supply highly material information and if the summary judgment record establishes that (1) the applicant knew of the information; (2) the applicant knew or should have known of the materiality of the information; and (3) the applicant has not provided a credible explanation for the withholding. See Bruno Indep. Living Aids, 394 F.3d at 1354; Critikon, Inc., 120 F.3d at 1257. Here, all three conditions are satisfied.

The CAFC did add comforting words for patent practitioners who will now be worried about submitting declarations with some undisclosed conflict of interest. The court stated flatly that:

In coming to this conclusion, we fully recognize that inventors often consult their colleagues or other persons skilled in the art whom they have met during the course of their professional life. Accordingly, when an inventor is asked to provide supportive declarations to the PTO, it may be completely natural for the inventor to recommend, and even contact, his own colleagues or people who are, or who have been, affiliated with his employer and to submit declarations from such people. Nothing in this opinion should be read as discouraging such practice. Rather, at least where the objectivity of the declarant is an issue in the prosecution, the inventor must disclose the known relationships and affiliations of the declarants so that those interests can be considered in weighing the declarations. This is not an onerous burden to place on any applicant.

Judge Newman dissented stating that:

“Inequitable conduct” in patent practice means misconduct by the patent applicant in dealings with the patent examiner, whereby the applicant or its attorney is found to have engaged in practices intended to deceive or mislead the examiner into granting the patent. It is a serious charge, and the effect is that an otherwise valid and invariably valuable patent is rendered unenforceable, for the charge arises only as a defense to patent infringement.

As this litigation-driven issue evolved, the law came to demand a perfection that few could attain in the complexities of patent practice. The result was not simply the elimination of fraudulently obtained patents, when such situations existed. The consequences were disproportionally pernicious, for they went far beyond punishing improper practice. The defense was grossly misused, and with inequitable conduct charged in almost every case in litigation, judges came to believe that every inventor and every patent attorney wallowed in sharp practice. This history was recently summarized as follows:

As is known, about 20 years ago inequitable conduct was frequently pleaded as a defense to patent infringement; a patent that is “unenforceable” due to a finding of inequitable conduct is dead. The defense was so misused by alleged infringers that the Federal Circuit once called this defense a “scourge” on US patent litigation . . . . The famous Kingsdown seemed to put a stop to the defense of inequitable conduct. . . .

See the entire opinion here.

The European Medicines Agency recommended approval of Omnitrope, which copies an existing growth hormone prescribed for undersized children. If given final OK by the European Commission, Omnitrope could be on the market later this year and would be the first-ever generic biotechnology drug. Omnitrope marks the first real threat to the near monopoly enjoyed by biotechnology drugmakers.

Generic biologics have been a tough fight in the U.S. as biotech drug makers say it would be dangerous to allow approval for biotech drugs since generics don’t have to perform expensive human tests but simply show their molecules are “equivalent” to existing drugs. The argument is that biotechnology drugs are made up of proteins, antibodies, and other substances derived from living cells, which can be extremely difficult, if not impossible, to reproduce exactly.

So far, the FDA has agreed. The Hatch-Waxman Act doesn’t include biologicals and the FDA has never issued any guidelines for getting biogenerics to market more quickly. While a single biotech drug can generate over $1 billon a year in revenues, biotechnology companies are coming under increasing pressure from possible generic competition due to high healthcare costs.

In the European case for Sandoz’ Omnitrope (somatropin), the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending to grant a marketing authorization for Omnitrope for treatment of growth disturbance and growth hormone deficiency. The active substance of Omnitrope is somatropin, a growth hormone produced by recombinant DNA technology. Somatropin is a hormone of importance for growth and for the metabolism of lipids, carbohydrates and proteins.

The Committee for Medicinal Products for Human Use (CHMP) issues specific guidelines concerning the scientific data to be provided to substantiate the claim of similarity used as the basis for a Marketing Authorization Application (MAA) for any biological medicinal product, e.g.: medicinal products containing biotechnology-derived proteins as active substance, immunologicals such as vaccines, blood-derived products, monoclonal antibodies, etc.

In principle, the concept of a “similar biological medicinal product” is applicable to any biological medicinal product. However, in practice, the success of such a development approach will depend on the ability to characterize the product and therefore to demonstrate the similar nature of the concerned products.

Biological medicinal products are usually more difficult to characterize than chemically derived medicinal products. In addition, there is a spectrum of molecular complexity among the various products (recombinant DNA, blood or plasma-derived, immunologicals, gene and cell-therapy, etc.). Moreover, parameters such as the three-dimensional structure, the amount of acido-basic variants or post-translational modifications such as the glycosylation profile can be significantly altered by changes, which may initially be considered to be ‘minor’ in the manufacturing process. Thus, the safety/efficacy profile of these products is highly dependent on the robustness and the monitoring of quality aspects.

Therefore, the standard generic approach (demonstration of bioequivalence with a reference medicinal product by appropriate bioavailability studies) is normally applied to chemically derived medicinal products. Due to the complexity of biological/biotechnology-derived products the generic approach is scientifically not appropriate for these products. The “similar biological medicinal products” approach, based on a comparability exercise, will then have to be followed.

Comparability exercises to demonstrate similarity are more likely to be applied to highly purified products, which can be thoroughly characterized (such as some biotechnology-derived medicinal products).

The ‘similar biological medicinal product’ approach is more difficult to apply to other types of biological medicinal products, which by their nature are more difficult to characterize, such as biological substances arising from extraction from biological sources and/or those for which little clinical and regulatory experience has been gained.

Whether a medicinal product would be acceptable using the ‘similar biological medicinal product’ approach depends on the state of the art of analytical procedures, the manufacturing processes employed, as well as clinical and regulatory experiences. The active substance of a similar biological medicinal product must be similar, in molecular and biological terms, to the active substance of the reference medicinal product.

The pharmaceutical form, strength and route of administration of the similar biological medicinal product should be the same as that of the reference medicinal product. When the pharmaceutical form, the strength or the route of administration is not the same; additional data in the context of the comparability exercise should be provided. Any differences between the similar biological medicinal product and the reference medicinal product will have to be justified by appropriate studies on a case-by-case basis.

CHMP guidelines are available here. (Guidance Documents / Biosimilar Products)

[This is the tenth and final post in a series of postings regarding the various proposals in the Patent Act of 2005.]

Post Grant Opposition Proceeding in the USPTO

On the third Tuesday of the month, if the moon is full, you may file an opposition to a patent grant. The actual provision is not quite so convoluted, thanks to a recent amendment, but there are definitely some timing issues that must be given their due! The Act proposes that a person may request that the grant or reissue of a patent be reconsidered by the USPTO by identifying the claims that are considered unpatentable and citing support thereof. The request must be made within 9 months of the grant of patent unless the patentee agrees otherwise (not too likely!). (See, Section 323 of the Act). The time limit parallels European patent practice and goes toward giving the patent holder some certainty, after the proscribed period, that their patent is no longer in danger of this type of challenge.

Aside from re-examination and interference proceedings, a third party’s ability, to challenge a patent grant, without resorting to litigation, is limited. The proposed procedure would allow the use of depositions and discovery to fully explore the validity of an issued patent; (See, Section 328 of the Act.) but, the failure of the non-patentee to prove their case carries estoppel issues similar to those under reexamination. (See, Section 336 of the Act.) Basically, the requestor is trading off his right to a jury trial on the factual issues of the case.

The Professional Inventors Alliance has expressed concern that this procedure might be misused to shift additional costs onto the patentee. They have also criticized the provision for its standard of proof, (See, Section 332 of the Act, which sets the standard at preponderance of the evidence rather than the clear and convincing standard offered in court which gives the patent holder an edge on the finding of validity.)ability to hide the real party in interest, (See, Section 322(a-b) of the Act: [T]he opposition shall proceed in the name of the real party in interest. [I]f requested by the opposer, the identity of a real party in interest shall be kept separate from the file of the opposition and made available only to Government agencies upon written request, or to any person upon a showing of good cause.) and the availability of the procedure to accused infringers after a patent lawsuit has been filed.

While their concerns are valid, it is clear that some alternative to the extreme costs of litigation is in order. The average cost of patent litigation ranges between $500,000 and $4,000,000 per party. (Statement of Michael K. Kirk, Executive Director American Intellectual Property Law Association, before the Subcommittee on Courts, the Internet, and Intellectual Property Committee of the Judiciary U.S. House of Representatives on the Patent Quality Improvement: Post-Grant Opposition (June 24, 2004)).

In addition, if it is only possible to test a patent’s validity through litigation if the patentee brings an infringement action against a competitor or provides the competitor with standing to bring a declaratory judgment action based on threats by the patentee …. a competitor cannot challenge a patent in litigation before the competitor incurs the costs and risks of developing and marketing a product. (Statement of Michael K. Kirk, Executive Director American Intellectual Property Law Association, before the Subcommittee on Courts, the Internet, and Intellectual Property Committee of the Judiciary U.S. House of Representatives on the Patent Quality Improvement: Post-Grant Opposition (June 24, 2004)). This means of limiting the inquiry to just the validity of the patent offers a compromise that will likely benefit everyone involved.

Submissions by Third Parties

35 U.S.C. §122(c) currently prohibits any protest or other form of pre-issuance opposition after publication without consent of the applicant although MPEP 1134.01 provides for a limited two-month window, following publication of a pending application, under which submissions may be made without comment. This proposal expands the window for submitting prior art against pending applications to six months after publication. It would also allow the third party to make arguments regarding such prior art in relation to the pending application. Yes, it does put a burden on non-patentees to keep an eye on their competitors’ patent doings but, if used, gives them a fairly cheap way to knock out rival patents and strengthen the patent system. It also benefits the patentee because they gain early knowledge of (and an opportunity to argue against) probative prior art. If the patent issues in spite of the submission, the patent holder has the security of knowing they have already survived a challenge to their patent from a competitor.

Venue

The original wording for this section raised a hue and cry because it clearly shifted the balance of power toward the defendant in litigation. It would only allow a lawsuit to commence in the district where the defendant resides or is located. Resource limited companies may be forced to file lawsuits far outside of their normal jurisdiction where they may find it difficult/expensive to assert their patent rights. (Robert B. Chess, on behalf of the Biotechnology Industry Organization, before the United States House of Representatives Committee on the Judiciary Subcommittee on Courts, the Internet, and Intellectual Property Hearing on: An Amendment in the Nature of a Substitute to H.R. 2795 the Patent Reform Act of 2005 (September 15, 2005)).

The amendment provides a facially more even-handed approach to venue. It directs the court to grant a motion for transfer to a more appropriate venue where a party to the action has substantial evidence or witnesses if the action was not brought in a district in which the patentee resides or maintains its principal place of business and, at the time the action was brought, neither the patentee nor the infringer had substantial evidence or witnesses in that judicial district.

Did you actually read all of that? The upshot is that most of the evidence regarding infringement will probably be in the judicial district associated with the defendant so the amendment is simply a more loquacious way of assigning venue to the defendant. Lucky for the patentee, there is always the Court of Appeals for the Federal Circuit.

Previous: Part 9. Prior User Rights.

Today’s post comes from Guest Barista Ria Schalnat, a registered patent attorney in Frost Brown Todd’s Cincinnati office.

A former University of Alabama professor is being sued by the University of Alabama System claiming that it owns his patents worth $197 million. The complaint was filed by The Board of Trustees of the University of Alabama against Nektar Therapeutics AL, Corporation, and Nektar Therapeutics in the United States District Court for the Northern District of Alabama alleges patent infringement, breach of contract license, violation of the Alabama Trade Secrets Act and unjust enrichment.

Dr. Milton Harris formed Nektar Therapeutics and developed a new inhalable insulin system. The U.S. Food and Drug Administration (FDA) has approved the inhalable formulation of recombinant human insulin [rDNA origin] powder for the treatment of adult patients with type 1 and type 2 diabetes mellitus, and conivaptan injection for the treatment of euvolemic hyponatremia in hospitalized patients. The insulin inhaler is not part of the suit.

The suit contends that because Harris was on the UA faculty from 1973 to 2000, and was covered by the university’s patent policy, his patents are owned by UA. The policy says it will be a university-owned patent if the discovery was made by UA employees and graduate students, through research paid for by the university, within an employee’s field or involving UA facilities.

Harris and another researcher developed a PEGylation technology, which was patented by UA. With PEGylation technology, polyethylene glycol (PEG) polymer chains are attached to a drug, which sustain bioavailability by protecting the drug molecules from immune responses and other clearance mechanisms. In an aqueous medium, the long, chain-like PEG molecule is heavily hydrated and in rapid motion. This motion causes the PEG to prevent the interference of other molecules. The university entered a royalty agreement with Harris for products developed out of the discovery, and Harris created Shearwater Polymers, a company bought by Nektar in 2001 for $197 million in cash and stock, to pursue manufacturing of PEG-related products.

The UA System claims that Harris, without UA’s knowledge, made a number of other discoveries related to the PEG technology in the following years and patented 28 of them. Harris was required to notify UA of any discovery related to the original PEG patent, and the lawsuit contends that the patents are “obvious derivatives” of and “equivalent” to the original PEG patent.

The lawsuit came about after Nektar informed UA last spring that it would no longer pay royalties from sales of the drug Neulasta, when Nektar informed the university that the PEG compound for Neulasta does not involve anything owned by UA

It may be necessary for the UA System to prove both ownership of the patents in question and that the products sold are covered by the patents in question.

[This is the ninth in a series of postings regarding the various proposals in the Patent Act of 2005.]

Prior User Rights

The proposed legislation expands the prior user rights defense. Currently, 35 U.S.C. 273(b) provides that it shall be a defense to infringement if the accused, acting in good faith, had actually reduced the subject matter of the patent being asserted to practice at least 1 year before the effective filing date of that patent AND commercially used the subject matter of the patent before the effective filing date of the patent – the sale or other disposition of a useful end product produced by a patented method qualifies as a commercial use. The proposed bill would expand this by striking the requirement that the infringement involve a “useful end product“.

This change would have the effect of extending the defense to methods of doing business. It also enhances the safe harbor for non-patentees in that they only have to beat the filing date of the patent application, through commercial use, rather than that date plus one year to qualify for the defense. The benefit of this provision is clearly directed toward the non-patentee but seems reasonable in our ultra-competitive country as it goes to the balance between trade secret protection versus patent protection.

Previous: Part 8. Inter Partes Reexamination.
Next Up: Part 10. Post Grant Oppositions, etc.

Today’s post comes from Guest Barista Ria Schalnat, a registered patent attorney in Frost Brown Todd’s Cincinnati office.