Patent Baristas

Recently, the courts looked at the question of whether separate enantiomers can have “first commercial marketing or use” status for purposes of patent term extension under 35 U.S.C. § 156. The U.S. Patent and Trademark Office, after consulting with the FDA, had granted an extension for US Pat. No. 5,053,407, which is exclusively licensed to Ortho-McNeil Pharmaceutical and is directed to an enantiomer of a racemic compound.

Under the Hatch-Waxman Act, a patent term extension is permitted for a patent that claims a drug that required regulatory approval prior to being put on the market (the Drug Price Competition and Patent Term Restoration Act, codified in part at 35 U.S.C. § 156 et seq.).

The district court agreed with the positions of the Patent and Trademark Office and the FDA, and held that the statutory requirements for term extension were met for the ’407 patent. The court then prevented Lupin Pharmaceuticals from making and selling the drug during the extended term of the patent. Needless to say, Lupin was crestfallen and appealed but the US Court of Appeals for the Federal Circuit affirmed the district court’s judgment in Ortho-McNeil Pharma v. Lupin Pharma (09-1362).

The ’407 patent is for an antimicrobial compound having the common name levofloxacin. Levofloxacin is the levorotatory enantiomer (also designated the S(-) enantiomer) of the racemate ofloxacin, which is a known antimicrobial product. A racemate consists of equal amounts of spatial isomers called enantiomers, molecules that are mirror images of each other.

Due to their spatial orientation, enantiomers are optically active and are characterized by whether they rotate plane-polarized light clockwise (dextrorotatory) or counter-clockwise (levorotatory). Although enantiomers and their racemates have the same chemical composition, they may differ in their physical, chemical, or biological properties. It is often the case that one of the enantiomers possesses a substantially greater portion, if not all, of the biological activity of the racemic mixture. This raises the question of the status of separated enantiomers as “new drug products” and whether they can be “first commercial marketing or use” if the racemate has previously been granted market approval, pursuant to 35 U.S.C. § 156(a)(5)(A).

The inventors determined that levofloxacin has properties that are significantly superior to those of ofloxacin. The ’407 patent describes this synthesis, and presents data showing that levofloxacin is more effective as an antimicrobial agent, more rapidly available for biological effectiveness, and has lower acute toxicity and thus may be administered in higher doses than ofloxacin.

The PTO concluded that extension of the patent term was warranted, and the PTO and FDA collaborated in calculation of the applicable extension of 810 days, in accordance with §156(d)(2)(A). Lupin the tried to block the extension under 21 U.S.C. §355(j)(2)(A)(vii)(IV) (Paragraph IV certification).

The law, in 35 U.S.C. §156(a), states that:

The term of a patent which claims a product, a method of using a product, or a method of manufacturing a product shall be extended in accordance with this section . . . , if– . . . (a)(4) the product has been subject to a regulatory review period before its commercial marketing or use; (a)(5)(A) except as provided in subparagraph (B) or (C) [not here relevant], the permission for the commercial marketing or use of the product after such regulatory review period is the first permitted commercial marketing or use of the product under the provision of law under which such regulatory review period occurred; . . .

The term “drug product” means the active ingredient of (A) a new drug, antibiotic drug, or human biological product (as those terms are used in the Federal Food, Drug, and Cosmetic Act and the Public Health Service Act), . . . including any salt or ester of the active ingredient, as a single entity or in combination with another active ingredient.

The issue was whether this was the first permitted commercial marketing or use of levofloxacin, as required by 35 U.S.C. §156(a)(5)(A), for the racemate had previously been marketed. The district court held that the extension was in conformity with the practices of the PTO and the FDA with respect to enantiomers, and that the PTO’s determination that levofloxacin is a different “product” than the racemate ofloxacin must be afforded “great deference.”

Lupin argued that the PTO and the FDA incorrectly interpreted the statute as far as enantiomers are concerned. Lupin insisted that an enantiomer is half of its racemate, and thus that the enantiomer levofloxacin was an “active ingredient” or component of the previously marketed racemate ofloxacin. That is, the racemate was merely a composition containing two drugs: the R and the S enantiomers. Thus, levofloxacin is the same “drug product” as ofloxacin meaning that levofloxacin was not “the first permitted commercial marketing or use of the product” as required by §156(a)(5)(A).

Ortho countered that an enantiomer has consistently been recognized, by the FDA and the PTO, as a different “drug product” from its racemate. The FDA practices were explained by Dr. David Lin, a former acting Division Director in the FDA’s Division of New Drug Chemistry, declaring that “in each and every instance in which it has considered the question, the FDA has described a racemate as a single active ingredient, distinct from its enantiomers, and each enantiomer as a single active ingredient distinct from the other and from the racemate.”

Lupin tried arguing that the status of enantiomers with was legislatively changed in 2007, in the statute that changed the FDA policy concerning data exclusivity for new enantiomer products. 21 U.S.C. §355(u)(1) (Supp. II 2008). The new provision authorizes an applicant “for a non-racemic drug containing as an active ingredient (including any ester or salt of the active ingredient) a single enantiomer that is contained in a racemic drug approved in another application” to, under certain conditions, “elect to have the single enantiomer not be considered the same active ingredient as that contained in the approved racemic drug.” Lupin felt that by specifically allowing an applicant to “elect” this separate treatment for enantiomers, Congress expressed its understanding that enantiomers were the same active ingredient as the racemate for all other purposes, including patent term extension.

The Federal Circuit said it couldn’t find any support for this theory in the legislative record, or elsewhere and affirmed the district court’s ruling that the ’407 patent on levofloxacin was properly granted the statutory term extension, for the enantiomer is a different drug product from the racemate ofloxacin, and was subject to regulatory approval before it could be commercially marketed and used.

This case clarifies that separate enantiomers can obtain independent patent protection and be entitled to patent term extension for “first commercial marketing or use” as new drug products. However, the Federal Circuit has said that patents for separated enantiomers can be invalidated on obviousness grounds.  So, pharmaceutical companies that can show (very?) good reasons that separation of enantiomers was not obvious can look forward to a much longer patent term – for now.

The Australian Patent Office (APO) is proposing official fee increases with effect from August 1, 2010.  Fees always go up (we don’t often get to report on fee decreases).  However, there is one new fee which will close off an existing loophole for avoiding excess claims fees.

Those who regularly prosecute applications in Australia should be aware that the APO applies an excess claims fee based on the claim count at the moment of allowance (the official fee is A$100 for each claim beyond the first 20 claims).

To date, it has been possible to delete claims prior to allowance in order to reduce the claim count, and then add back the deleted claims after allowance.  However, the APO is now proposing a new fee which will apply in circumstances where an applicant adds back claims after allowance (the proposed new fee is A$100 for each added claim beyond the first 20 claims).

If you wish to take advantage of this loophole, then you should expedite prosecution such that the amendment to “add back” excess claims occurs before August 1, 2010.

The official announcement can be seen here.

(via Bill Bennett, Partner at Pizzeys in Australia)

The Pharmacy Technician Certification blog posted its round-up of the 50 Best Twitter Feeds for Pharma News.  While there is no shortage of feeds you can find in pharma, this list provides a breakdown of the best feeds in various categories.

Best Pro Twitter Feeds for Pharma News include:

Best Individual Twitter Feeds for Pharma News include

Best Science Twitter Feeds for Pharma News include:

Best Company Twitter Feeds for Pharma News include:

Let us know if there are any feeds you prefer!

The Japanese Patent Office (“JPO”) introduced a revised version of the “Examination Guidelines for Medical Inventions,” in October of 2009.  The revised guidelines are applicable to all patent applications being examined after November 1, 2009, including pharmaceutical products and medical devices.

Methods for Collecting data from the human body

In Japan, the examination guidelines stipulate that patentable inventions must be “industrially applicable inventions.” Prior to the revision, a method to gather data from the human body for diagnostic purposes was not eligible for patent rights since it was not considered an industrially applicable subject matter.

Under the current examination guidelines, the above can be granted patent rights as long as it does not include a diagnostic step or process in the claims.

For example, the following claims are patentable according to the revised guidelines:

1. A method of collecting oral mucous membrane for diagnosing influenza.
2. A method for taking X-ray images of lung.
3. A method for measuring body tempera­ture by inserting an ear thermometer into the external ear.

Medicaments with a new dosage regimen

Under the revised guidelines, medicinal inventions with new dosages, dosage intervals, administration routes (e.g. intravenous vs. sublingual) or administration sites of known compounds are treated as medicinal uses which impart novelty to a claim over the prior art and are patentable so long as the claimed invention is not obvious over the prior art.

According to the revised guidelines, the following examples are considered inventive since changing the dosage and mode of administration of the medicine shows “a remarkable effect beyond that which is expected by a person skilled in the art.”: Under the revised guidelines, the inventions presented below are considered “inventive” since they would impact a consumer’s quality of life:

Example A:

Prior Art: It has been known that asthma is treated with 1 pg/kg body weight per day of compound A and is frequently accompanied by side effect B.
Present Invention: It was found that asthma symptoms improved over a long period of time by orally administering 30-40µg/kg of compound A once every 3 months while reducing the incidence of side effect B.

Example B:

Prior Art: It has been known that compound A shows growth-inhibitory effects against ovarian cancer when given intravenously, while giving rise to hepatotoxicity as a side effect.
Present Invention: It was found in this invention that the blood level of hormone Y secreted from the pituitary gland changed when administering comp und A to a particular site Z in the human brain, which had the effect of significantly diminishing ovarian cancer compared to the conventional treatment of intravenous administration.

This revision broadens the scope of patentable subject matter and stimulates research and development in the pharmaceutical industry. Furthermore, the revision encourages research and development of medical products with minimized side effects and enhanced patient compliance.

Today’s post is by Guest Baristas by Toyomi Ohara. a US patent agent and Technical Advisor, and Sara Rosengard, an International Liaison, both with Kéisén Associates, a Tokyo-based Japanese intellectual property law firm.

A recent decision by the Supreme Court of the United States may now allow copyright owners to bring a lawsuit without securing a federal copyright registration—though the issue is not wholly resolved. On March 2, 2010, the Supreme Court unanimously held that, although the registration requirement found in § 411(a) of the Copyright Act is a precondition to filing a copyright infringement claim, the requirement is not “jurisdictional” in nature. A copyright holder’s failure to comply with that requirement does not restrict a federal court’s subject matter jurisdiction over infringement claims involving unregistered works. The Supreme Court’s opinion, however, leaves unanswered questions regarding § 411(a)’s impact on litigants who have not registered their works with the Copyright Office. Reed Elsevier, Inc. v. Muchnick, 130 S.Ct. 1237 (2010).

Section 411(a) and the Courts before Muchnick

Section 411(a) states that “no action for infringement of the copyright in any United States work shall be instituted until preregistration or registration of the copyright claim has been made,” subject to only a very limited exception. Before the Supreme Court’s ruling in Muchnick, the lower courts interpreted § 411(a) as a “jurisdictional” bar to bringing suit; if the plaintiff did not have a copyright registration in place, the court did not have jurisdiction over the case. In such instances, the court—even without the request of the defending attorneys—was obligated to dismiss the case because the court lacked jurisdiction over the subject matter of the case.

The Muchnick Case

The Muchnick case began as a copyright infringement class action suit initiated by freelance authors against various publishers that the authors claimed reproduced the authors’ works into their online databases without obtaining permission. Some of the authors’ works were registered with the Copyright Office; others were not.

The parties to the case reached a settlement agreement, which allowed authors with registered works to receive higher compensation than those with unregistered works. Author Muchnick and nine others, who had unregistered works, objected to the terms of the settlement and appealed the case to the Second Circuit. The Second Circuit held that the settlement was invalid because, under § 411(a), the District Court lacked subject matter jurisdiction over the claims related to the unregistered works.

The Supreme Court agreed to hear the case and held that § 411(a)’s registration requirement is not “jurisdictional” and, therefore, did not prevent the District Court from ordering the settlement agreement related to registered and unregistered works. Following the bright-line rule announced in the 2006 Arbaugh v. Y & H Corp. decision, the Supreme Court found that Congress did not expressly state that § 411(a) is a jurisdictional requirement; without an express statement, the rule is not “jurisdictional.”

What is “Jurisdictional?”

A violation of a jurisdictional rule may be raised by any litigant at any time during litigation— including when the case is on appeal. The courts must also police compliance of jurisdictional rules sua sponte, upon the courts’ own prerogative. Further, jurisdictional rules are not subject to waiver or consent, equitable principles, or forfeiture.

Because § 411(a) is no longer “jurisdictional,” the court now allows federal trial courts to approve settlements involving both registered and unregistered works. Additionally, the Eleventh Circuit’s doctrine that prohibited plaintiffs from seeking declaratory judgments of non-infringement when the plaintiff did not have a copyright registration may no longer bar plaintiffs from seeking declaratory relief.

Unanswered Questions

What is left to be determined is, if not “jurisdictional,” what kind of requirement § 411(a) is and how it will affect future copyright infringement litigation. Section 411(a) will likely still provide a mechanism for defendants to quickly and easily dismiss an action involving unregistered works, albeit on non-jurisdictional grounds. The question, however, remains as to whether a defendant may waive the registration requirement so that it may go ahead and defend its case in the first action filed rather than wait for the plaintiff to obtain a registration and sue them again. It is also unclear whether courts will now allow cases to proceed when the plaintiff has filed an application but is still awaiting the registration certificate from the Copyright Office. Finally, it is unclear whether trial courts may be able to provide some equitable exceptions to the registration requirement and whether the trial courts may dismiss claims based on unregistered works without waiting for the defendants’ motions.

Today’s post is by Guest Baristas Melissa Kern and Austin Padgett, attorneys in Frost Brown Todd’s Trademark/Copyright Law Practice Group.

Health care reform has produced a new tax credit and grant program for inventive small to mid-sized companies with R&D in therapeutics. Federal tax credits and grants will be awarded up to a national total of $1 billion for tax years 2009 and 2010 for winning, qualifying biotech projects.

Companies with 250 or fewer employees are eligible, if they have a “qualifying therapeutic discovery project” designed to do any of the following:

• treat or prevent diseases or conditions through pre-clinical activities, or clinical trials or studies (or carrying out research protocols) aimed at securing approval of a drug or biologic;
• diagnose diseases or conditions or determine molecular factors concerning disease or conditions through molecular diagnostics or drugs to guide therapeutic decisions; or
• develop process, technologies or products to further therapeutic administration or delivery.

Regulations and application forms will be issued in mid-May. Companies should start preparing now, as early submittals are most likely to receive awards. The IRS will select winning applications and distribute funds in the form of tax credits or cash grants.

The tax credit or grant is available for “qualified investments” made in the 2009 and 2010 tax years. The qualified investment for a tax year is the aggregate amount of costs paid or incurred in that tax year for expenses necessary for and directly related to conducting the project. The amount of credit or grant a business can receive is equal to 50% of the qualified investment in the project.

Thus a biotech company that has a tax liability can see its tax bill slashed and a business that has no tax liability can receive a nontaxable grant for the same amount. With this new provision a biotech business can look to put big money in its pocket immediately. If your company makes a qualified investment of $1 million, it gets a $500,000 tax credit or a $500,000 check.  What’s not to like?

Favored projects will include those that show reasonable potential to help cure cancer, create new therapies in the area of unmet medical need, treat chronic or acute disease, or reduce long-term health care costs in the United States. Projects that have high U.S. job-creation potential and will advance U.S. competitiveness will also have an advantage.
Because this is a competition, careful preparation of the applications required is essential.

If you want to receive prompt details of the Treasury’s application process and standards for certification when announced (by May 22), please drop us an email.

The Vatican is throwing its support behind an international project for adult stem-cell research but is not directly involved and has made no financial contribution to the initiative.

The project, led by the University of Maryland School of Medicine in Baltimore, comprises a consortium of researchers from several Italian health institutes, including the Vatican-owned Bambino Gesu Hospital in Rome.

Embryonic stem cells are valuable for their pluripotence, which is believed to be the key to discovering treatments for degenerative diseases. However, the Church opposes embryonic stem-cell research because it involves the destruction of embryos.

The Church supports adult stem-cell research, which uses undifferentiated cells obtained from adult organs and tissues. Although the Church has been criticized for maintaining this position, the Vatican is resolute that there are alternative research avenues, such as working with adult stem cells, that should be pursued.

The current research project will investigate the use of intestinal adult stem cells for treating disease. Intestinal stem cells are highly active, adaptable cells, which are pre-programmed to generate all cells necessary for intestinal functioning, such mucus cells or epithelial cells. In addition, these cells are relatively easy to harvest from the donor through a routine procedure such as endoscopy.

Patients with celiac’s will be first to be studied.

Issue 1 is a statewide ballot measure on the May 4 primary ballot that will renew and continue Ohio’s successful economic development and jobs creation program, the Ohio Third Frontier initiative. A public-private partnership created in 2002 with bipartisan leadership and support, Third Frontier makes targeted state investments in promising technologies, research and entrepreneurs – and builds new companies, supports business expansions and creates new jobs.

The current funding mechanism for Third Frontier, approved by Ohio voters in 2005, expires in 2012. A “YES” vote on Issue 1 will authorize $700 million in bonds to extend funding for this successful program for another four years, through 2016. Issue 1 will not raise taxes.

With Election Day less than two weeks away, there is a quick and easy way for YOU to help build support for Issue 1 by letting your friends, family and co-workers know why you’re voting YES on May 4 – and urging them to do the same.

Join the e-Postcard Campaign!

Visit http://www.unitedforjobsohio.com/send-an-e-postcard to send a “Vote YES on Issue 1” e-postcard to help the Get Out The Vote efforts. The e-postcard comes with a short, pre-written message about the benefits of Issue 1 and the Ohio Third Frontier:

Dear Recipient’s Name,

I am sending you this e-postcard to encourage you to vote YES on Issue 1 on May 4th to renew the Ohio Third Frontier program, which has created more than 48,000 jobs and helped launch more than 500 new companies across Ohio. A YES vote on Issue 1 will renew the program and create tens of thousands more jobs in our state without raising taxes.

Issue 1 is our opportunity to secure a better future for our state, ourselves and our children. Please join me in voting YES on Issue 1 on May 4.

Sincerely,
Your Name

Simply visit the link above and enter the names and e-mail addresses of ten friends you would like to send your e-postcard to.  You also can let your friends know about Issue 1 by inviting them to become a fan on Facebook or follow the campaign on Twitter.

More info here:

• Official Ballot Language (PDF – 14.2 KB)
• Official Explanation (PDF – 9.3 KB)
• Official “For” argument (PDF – 66.6 KB)