Patent Baristas

I’ve said it before and I’ll say it again, if you do research you must keep meticulous notes of the inventive process. Laboratory notebooks often play an important role during the patent prosecution process and even after a patent has issued. A properly kept notebook is invaluable in cases in which another party claims a patent to be invalid or in interference cases in which two or more patents have been issued on the same invention and the true inventor must be ascertained.

In Yeda Research And Development Co. v. ImClone Systems and Aventis Pharmaceuticals (03 Civ. 8484), a federal judge ruled that three scientists from Israel are the true inventors of a patent used for ImClone Systems‘ cancer drug Erbitux rather than the seven people listed on the patent after finding no documentary evidence suggesting that any of the other named inventors contemplated the claimed invention. ImClone, as you know, is the company whose founder, Sam Waksal, is serving a prison sentence for his role in the stock scandal that also involved Martha Stewart. In a lengthy, 140-page opinion the court found the Yeda scientists had proved they were entitled to sole inventorship of the patent.

Yeda sued ImClone and Aventis alleging improper inventorship of U.S. Pat. No. 6,217,866, entitled “Monoclonal Antibody Specific to Human Epidermal Growth Factor Receptor and Therapeutic Methods Employing Same.” Yeda is the assignee of the legal interests of three scientists (Sela, Pirak and Hurwitz – collectively, the “Weizmann scientists”), who maintain that they are the true inventors of the ‘866 patent. ImClone is the assignee of the interests from the named inventors.

Earlier, the named inventors created two monoclonal antibodies for use as research tools and gave samples of the antibodies to the Weizmann scientists. The Weizmann scientists performed experiments with the antibodies and discovered that when one of the two antibodies, known as mAb 108, was administered in vivo in a mixture with chemotherapy drugs, the effect on human tumor cells was synergistic.

One named inventor, Schlessinger, testified that he “knew” that this mixture experiment would be performed based on his knowledge of Hurwitz’s prior work. Hurwitz, however, testified that the Weizmann scientists only decided to conduct the mixture experiment more than a year after the research began.

Soon after the discovery, Schlessinger was told of the discovery and sent a draft manuscript. Meloy Labs (later became Rorer then part of Aventis) began pursuing patent protection for both the antibodies themselves and for the method of administering them with chemotherapy drugs that had been developed by the Weizmann scientists. Only the scientists employed by Meloy/Rorer were included as inventors on its patent applications. Not only that, Meloy/Rorer and later, ImClone, directly copied the text and figures from the manuscript into their patent applications.

During prosecution, the USPTO also raised questions about the fact that the patent application seemed to be drawn directly from work done by the Weizmann scientists. Defendants overcame this objection by suggesting that they had entirely conceived of the research conducted by the Weizmann scientists, who had simply followed their directions as to what experiments to perform.

The issued patent only included those claims drawn to the method of administering an antibody in a mixture with chemotherapy drugs; the PTO did not permit the antibodies themselves to be patented. The issued ‘866 patent claims:

1. A method for inhibiting the growth of human tumor cells that express human EGF receptors and are mitogenically-stimulated by EGF, the method comprising administering an effective amount of an anti-neoplastic agent to a human cancer patient having said tumor cells; (i) wherein said antibody binds to the extra-cellular domain of the human EGF receptor of said tumor cell; (ii)wherein the antibody is not conjugated to the anti-neoplastic agent; and (iii) wherein the antibody inhibit [sic] the binding of EGF to the EGF receptor.

ImClone obtained FDA approval for the treatment of certain types of human cancer, permitting it to distribute Erbitux under the protection of the ‘866 patent. As of the date of trial, ImClone had received about $900 million in revenues under a distribution agreement with Bristol Myers Squibb.

The court looked at (a) which scientists invented the subject matter of the ‘866 patent; and (b) whether the affirmative defense of laches is available to ImClone.

In looking at inventorship, the court said it must begin “with a construction of each asserted claim to determine the subject matter encompassed thereby.” Trovan Ltd. v. Sokymat SA, Irori, 299 F.3d 1292, 1302 (Fed. Cir. 2002) (citations omitted). After defining the invention, the Court “is then to compare the alleged contributions of each asserted co-inventor with the subject matter of the properly construed claim to then determine whether the correct inventors were named.” Id. (citing Ethicon, Inc. v. U.S. Surgical Corp., 135 F.3d 1456 (Fed. Cir. 1998)).”

Disturbingly, one of the determining factors cited by the court was the defendant having too good of a memory! The court stated that:

We find Schlessinger’s account of this conversation not credible for several reasons. First, nearly twenty years have passed since the conversation occurred, such that we doubt Schlessinger remembers its details, especially considering the contorted testimony Schlessinger offered on cross-examination, in which he seemingly attempted to “remember” those details that would bolster defendants’ case.

I’m not sure what that means for future cases – perhaps prepping witnesses to not remember so good? However, the court also noted that “despite providing the Court with hundreds of exhibits, defendants have failed to present a single piece of physical or documentary evidence suggesting that Schlessinger or any of the other named inventors contemplated that any particular type of testing would be conducted.”

ImClone also argued that the legal doctrine of laches bars Yeda’s claims in light of the fact that the lawsuit was initiated more than a decade after defendants first submitted an application for a patent. The affirmative defense of laches applies when: (1) a plaintiff unreasonably delays bringing suit; and (2) the delay results in material prejudice to a defendant.

Laches is an equitable defense, and is thus committed to the sound discretion of the trial judge. The period of delay is measured from when the claimant had actual notice of the claim or would have reasonably been expected to inquire about the subject matter, i.e., “knew-or-should-have-known.” But, ImClone was sunk given that the court found the defendants at fault, stating:

Because we find that defendants’ hands are unclean, i.e., they are responsible for plaintiff not finding out about their patent applications, the laches defense is unavailable to defendants.

In finding for Yeda, the court held that:

Having considered all of the evidence, we now find that the Weizmann scientists are entitled to sole inventorship of the ‘866 patent. In so holding, we make the following factual determinations, all of which are discussed at length infra: (1) Schlessinger did not give Hurwitz specific information regarding the properties of the antibodies or any intended uses; (2) Schlessinger did not specifically contemplate that the Weizmann scientists would perform the mixture experiment that forms the basis for the ‘866 patent; (3) the named inventors’ creation of the antibodies used by the Weizmann scientists does not entitle them to inventorship; (4) the Weizmann scientists solely conceived of the idea embodied in the ‘866 patent; and (5) in light of the defendants’ unclean hands, i.e., their copying from the Weizmann scientists’ draft paper and their efforts to prevent Yeda from discovering defendants’ patent applications, Yeda did not unreasonably delay asserting its rights relative to the ‘866 patent.

ImClone is now considering a three-way strategy for dealing with the decision including an appeal of the court decision, a motion to invalidate the patent turned over to three Israelis and exercising an option to license the patent from Yeda Research & Development Co.

See my suggestions on documenting inventions here.

AstraZeneca filed a request for an advisory opinion from the FDA pursuant to 21 C.F.R, § 10.85, asking whether patents directed to drug delivery systems, such as inhalation devices, that do not recite the approved active ingredient or formulation should be listed in the “Approved Drug Products With Therapeutic Equivalence Evaluations” (“Orange Book“).

21 C.F.R. § 314.53 requires that New Drug Application (“NDA”) applicants submit for listing in the Orange Book the patent numbers and expiration dates of any patent that claims the drug or a method of using the drug that is the subject of the NDA “with respect to which a claim of patent infringement could reasonably be asserted… .”. The regulation states that patents that claim the “drug product” that is the subject of the NDA must be listed, but also states that patents claiming “packaging” must not be listed.

Earlier, the FDA published its final rules, Applications for FDA Approval to Market a New Drug: Patent Submission and Listing Requirements and Application of 30-Month Stays on Approval of Abbreviated New Drug Applications Certifying That a Patent Claiming a Drug is Invalid or Will Not Be Infringed, 68 Fed. Reg. 36676 (June 18, 2003).

In the rules, the FDA stated that drug products include “metered aerosols,. . . metered sprays . . . and pre-filled drug delivery systems” and that patents claiming such drug products should be listed in the Orange Book and noted that “[t]he key factor is whether the patent being submitted claims the finished dosage form of the approved drug product.” The FDA didn’t directly address whether patents directed to drug delivery systems that do not recite the approved active ingredient or formulation should be listed in the Orange Book.

GlaxoSmithKline asked the same question in January 2005, asking:

“If the patent claims a drug delivery device or elements of a drug delivery device approved as part of a New Drug Approval (“NDA”), but the patent does not specifically claim the active ingredient or mention the active ingredient or ingredients contained in the approved drug product, or if a patent claims the protective overwrapping of a drug delivery device, should information concerning that patent be submitted to the FDA for listing in the Orange Book?”

The FDA has not responded to GSK’s request. In attempt to set out its intent, AstraZeneca summed up the request with the statement: “AstraZeneca will continue to list them unless it receives guidance from FDA that such listings are improper.”

Ariad Denied Declaratory Judgment

Ariad Pharmaceuticals announced that the United States District Court for the District of Delaware denied their motion to dismiss the lawsuit filed by Amgen relating to their products Enbrel(R) and Kineret(R). In the lawsuit, Amgen is seeking a declaratory judgment that these products do not infringe U.S. Patent No. 6,410,516, covering methods of treating human disease by regulating NF-κβ cell-signaling activity, and that the patent is invalid and that Amgen has not infringed any of the claims of the ‘516 Patent based on activities related to Amgen’s products, Enbrel® and Kineret®. As we’ve said earlier, this is far for over.

Stanford to Ban Drug Makers’ Gifts to Doctor

Stanford University Medical Center announced Tuesday it is joining a small group of academic medical centers in banning its physicians from accepting industry gifts of any size, including drug samples, free meals, free tickets to sporting events, free pens or any of the other freebies showered on doctors by drug companies. This is a start but only a drop in the bucket for an industry that spends $21 billion per year on marketing.

Anti-Patent Attorney Dan Ravicher Campaigns Against Over-Broad Software Patents

Dan Ravicher, of the Public Patent Foundation, is interviewed in MIT’s Technology Review.

TR: How are these patents on standards abused? Can a patent holder, regardless of the legal outcome, inflict damage on a developer?

DR: In a lot of software patent cases we’ve seen, the patent holder ends up losing — but only in court. But that doesn’t mean the developer didn’t lose a substantial amount of time and money and distraction. Simply because many software developers are resource-deprived, they’re denied a fair day in court to prove their innocence.

FTC Keeps Up Fight Against Generic Settlements

After losing lost a court challenge in 2005 and the Supreme Court declined to hear its appeal, the Federal Trade Commission is continuing its fight against settlements by drug companies to delay generic entry to the market. FTC Chairman Deborah Platt Majoras said “There is no question we’ve taken some hits on this,” But “we are not walking away.”

Pfizer Wins in Challenge to Norvasc Patent

Pfizer said a federal District Court upheld Pfizer’s patent covering amlodipine besylate, the active ingredient in Norvasc, a medicine for treating hypertension. The generic manufacturer, Synthon Pharmaceuticals, had challenged the patent. The court ruled that the patent (U.S. Patent No. 4,879,303) covering amlodipine besylate is valid and infringed by the generic manufacturer’s product and can keep Synthon from launching a generic version until September 2007.

Materials, Medicine, and Nanotechnology Summit

The Materials, Medicine, and Nanotechnology Summit will be hosted by Cleveland Clinic, ASM International, and the Nano-Network as the anchor event of Nano-Weekâ„¢ 2006, a five-day exploration of how nanotechnology is changing our world. The Summit is comprised of the biennial Cleveland Clinic NanoMedicine Summit and ASM’s Materials & Processes for Medical Devices (MPMD) Conference and Exposition.

In a follow-up to my discussion on the Alza case, it is important to note that the U.S. Supreme Court agreed to review an appeal of a key patent case that could set a standard for when an invention is obvious. The Court has taken up the appeal by KSR International Inc., a Canadian manufacturer of gasoline pedals for cars and light trucks, arguing that a patent held by a rival manufacturer is invalid because it was obvious at the time it was patented.

In Teleflex Inc. v. KSR Intern. Co. (Fed. Cir. 2005), the CAFC held that when combining two or more references in an obviousness finding, there must be a suggestion or motivation to combine the teachings. This “teaching-suggestion-motivation test’ has been applied by the Federal Circuit in hundreds of cases since set out in 1985. The Federal Circuit applies this test even where a patent claims nothing more than a combination of pre-existing, off-the-shelf components in which each component performs exactly the same function that it had been known and was designed to perform.

In KSR, the Federal Circuit held that the prior art did not render the claimed invention unpatentable because they had not proven, beyond genuine dispute and by clear and convincing evidence, that there was a suggestion or motivation to combine the teachings of the prior art in the particular manner claimed by the patent at issue (U.S. Patent No. 6,237,565).

Now, the Supreme Court has granted cert in KSR Intern. Co. v. Teleflex Inc., Supreme Court No. 04-1350. In its Petition For A Writ Of Certiorari, KSR presented the following question:

Whether the Federal Circuit has erred in holding that a claimed invention cannot be held obvious, and thus unpatentable under 35 U.S.C. § 103(a), in the absence of some proven “‘teaching, suggestion, or motivation’ that would have led a person of ordinary skill in the art to combine the relevant prior art teachings in the manner claimed.”

This case raises a question of broad and general importance: What is the proper interpretation of the patentability standard set forth in § 103 of the Patent Act? The answer to this question affects every pending U.S. patent application, every issued U.S. patent, and every U.S. federal court challenge to the validity of a patent.

Section 103 was first enacted in 1952; it provides that a patent cannot issue on subject matter that would have been “obvious” to a hypothetical “person having ordinary skill in the art” or PHOSITA. Four factual inquiries underlie an evaluation of obviousness: (1) the scope and content of the prior art; (2) the differences between the claimed invention and the prior art; (3) the level of ordinary skill in the art; and (4) any other objective indicia of non-obviousness, such as commercial success of the claimed invention, long felt but unmet need.

KSR argues that under the Supreme Court’s interpretation of § 103, a combination of pre-existing elements does not constitute an “invention”, and does not meet the “condition for patentability” specified in § 103(a), if each element in the claimed combination does nothing more than what it was previously known or designed to do. They argue that the Federal Circuit’s interpretation of § 103 is wrong in holding that a combination of pre-existing elements will always constitute an “invention”, and will always meet the “condition for patentability” specified in § 103, unless there is proven “some ‘suggestion, teaching, or motivation’ that would have led a person of ordinary skill in the art to combine the relevant prior art teachings in the manner claimed.” They argue that the “teaching-suggestion-motivation test” has no basis in the text of § 103 or in any decision of the Supreme Court.

It seems Alza was the Federal Circuit’s attempt to shore up it reasoning behind the test with their statement that obviousness is a question of law, reviewed de novo, based upon underlying factual questions while the presence or absence of a motivation to combine references in an obviousness determination is a question of fact.

This is of particular importance to pharmaceutical and biotechnology research-based companies who are against any change to the test (and might make it difficult to patent known drugs for new uses).

Dennis Crouch’s Patently-O has more details on the case, including links to filings and briefs.

I will be attending the BIO Mid-America VentureForum on September 26-27 in Cleveland, OH. The VentureForum, co-hosted by Omeris, is the Midwest’s largest annual event for bioscience and medical device product and platform companies from across the country. Approximately 75 companies seeking seed, early-and late-stage funding will make presentations.

If you will be attending the VentureForum and would like to meet, just drop me a line. I’d love to have the opportunity to chat over coffee with anyone.

E-Mail Me:

Speakers at the conference include:

Ohio Governor Bob Taft
Mark Collar, President Global Pharmaceuticals & Personal Health, The Procter & Gamble Company
John Huston, Founding Member, Ohio Tech Angel Fund
Peter Kleinhenz, Managing Director, CID Capital
Gil Van Bokkelen, Ph.D., Chairman & CEO, Athersys
John Rice Ph.D., Managing Partner, Triathlon Medical Ventures
Lynn Allen, President, Capital Innovations, Inc.
Alfred Brown Ph.D., President, BCM Technologies
Thomas Bradshaw, President and CEO, Ricerca Biosciences
Joseph Hahn, M.D., Chief of Staff, The Cleveland Clinic Foundation
Donald Harrison, M.D., Managing Director, Charter Life Sciences
Fred Rothstein, M. D., President and CEO, University Hospitals
Patrick McBrayer, President and CEO, AxioMed Spine Corporation
Walter Plosila, Ph.D., VP, Technology Partnership, Battelle Memorial Institute

Tech entrepreneurs in Cleveland should check out FastTrac Tech, a two-phase, multi-session, hands-on program where you will use your business as a case study, giving you the opportunity to put proven business practices to work.

Alza Corp. appealed a district court’s finding of noninfringement and invalidity of claims 1-3, 11, 13 and 14 of U.S. Patent No. 6,124,355 for a generic version of the once-a-day extended release formulation of the anti-incontinence drug oxybutynin, which Alza has been marketing as Ditropan XL®. Alza had sued after Mylan and Impax filed ANDAs for generic once-daily, controlled-release oxybutynin formulations.

The ‘355 patent claims:

A sustained-release oxybutynin formulation for oral administration to a patient in need of treatment for urge incontinence comprising a therapeutic dose of an oxybutynin selected from the group consisting of oxybutynin and its pharmaceutically acceptable salt that delivers from 0 to 1 mg in 0 to 4 hours, from 1 mg to 2.5 mg in 0 to 8 hours, from 2.75 to 4.25 mg in 0 to 14 hours, and 3.75 mg to 5 mg in 0 to 24 hours for treating urge incontinence in the patient.

The district court found that Alza had failed to meet its burden of proof on infringement. The district court also found the asserted claims of the ‘355 patent to be invalid as both anticipated and obvious in light of the prior art. The Federal Circuit agreed in Alza v. Mylan (Fed. Cir. 2006, 06–1019).

The standard for obviousness is that a claimed invention is unpatentable if the differences between it and the prior art are “such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art.” 35 U.S.C. § 103(a) (2000); In re Kahn, 441 F.3d 977, 985 (Fed. Cir. 2006) (citing Graham v. John Deere Co., 383 U.S. 1, 13-14, (1966)).

Obviousness is a question of law, reviewed de novo, based upon underlying factual questions while the presence or absence of a motivation to combine references in an obviousness determination is a question of fact.

The “motivation to combine” requirement prevents hindsight reasoning when determining the obviousness of an invention. The CAFC pointed out that according to the “motivation-suggesting-teaching” test, a court must ask “whether a person of ordinary skill in the art, possessed with the understandings and knowledge reflected in the prior art, and motivated by the general problem facing the inventor, would have been led to make the combination recited in the claims.” Kahn, 441 F.3d at 988 (citing Cross Med. Prods., Inc., v. Medtronic Sofamor Danek, Inc., 424 F.3d 1293, 1321-24 (Fed. Cir. 2005)).

The CAFC repeated the analysis in Kahn:

A suggestion, teaching, or motivation to combine the relevant prior art teachings does not have to be found explicitly in the prior art, as “the teaching, motivation, or suggestion may be implicit from the prior art as a whole, rather than expressly stated in the references. . . . The test for an implicit showing is what the combined teachings, knowledge of one of ordinary skill in the art, and the nature of the problem to be solved as a whole would have suggested to those of ordinary skill in the art.” However, rejections on obviousness grounds cannot be sustained by mere conclusory statements; instead, there must be some articulated reasoning with some rational underpinning to support the legal conclusion of obviousness. This requirement is as much rooted in the Administrative Procedure Act [for our review of Board determinations], which ensures due process and non-arbitrary decision-making, as it is in § 103.

In the present case, the patent at issue is directed to an extended release form of oxybutynin. After roughly 8-12 hours a typical drug dosage form will reach the colon. If, hypothetically, a particular drug is simply not absorbed from the colon into the bloodstream, then it may make little sense to develop an extended-release dosage form that is capable of “withholding” the release of some fraction of that drug until it reaches the colon. In other words, under these hypothetical conditions, there may be little motivation to design an oral dosage form capable of releasing drug more slowly than over an approximately 8-12 hour time course, because such drug would be released in the colon, where it is (hypothetically) not absorbed.

The ‘355 patent claims an extended release oxybutynin formulation, which Alza argued one of ordinary skill in the art would not have believed that oxybutynin could be absorbed in the colon. Absent such absorption, Alza contends that one of ordinary skill in the art lacked the motivation to make the claimed extended release formulation.

The CAFC was not persuaded. Although the district court based its invalidity holding both on anticipation and obviousness grounds, the CAFC affirmed based only on obviousness.

Because Alza’s argument was that no one of ordinary skill in the art would have been motivated to adapt the known technology to oxybutynin in the first place, because a person of ordinary skill in the art would have had no reason to expect that such an extended release oxybutynin formulation would have therapeutic value, the CAFC merely looked at whether one of ordinary skill in the art in 1995 would have had a reasonable expectation that oxybutynin would be colonically absorbed and therefore would have been motivated to produce the claimed extended release formulation.

Alza argued that the district court erred when it concluded that the evidence established that a person of ordinary skill in the art in 1995 would reasonably expect oxybutynin to absorb in the colon and have a reasonable expectation of success of producing a 24 hour oxybutynin formulation meeting the claims of the ‘355 patent. Alza argued that there was no contemporaneous documentation supporting the view that any one factor—lipophilicity or anything else—existed to identify successful candidates for once-a-day delivery.

The CAFC set out that:

As an initial matter, it is essential to recognize that, as we have explained above, under our non-rigid “motivation-suggesting-teaching” test, a suggestion to combine need not be found in the prior art. See Cross Med. Prods., 424 F.3d at 1322 (“[T]he motivation to combine need not be found in prior art references, but equally can be found in the knowledge generally available to one of ordinary skill in the art . . . .”). Accordingly, where the testimony of an expert witness is relevant to determining the knowledge that a person of ordinary skill in the art would have possessed at a given time, this is one kind of evidence that is pertinent to our evaluation of a prima facie case of obviousness. We now turn to consider whether the relevant evidence, including the expert testimony and the prior art, when viewed as a whole supports the findings of the district court. We conclude that the findings of the district court were not clearly erroneous.

Mylan’s expert, Dr. Amidon, testified that based on its lipophilicity, he would “expect oxybutynin to be a highly permeable” compound that is “rapidly absorbed” along the length of the GI tract, including the colon.

In looking at the references cited by Alza to refute the testimony, the Court concluded that:

Far from teaching away or detracting from the weight of Dr. Amidon’s testimony, these prior art references, taken as a whole, are entirely consistent with the finding that in 1995 a person of ordinary skill in the art would have expected a general, albeit imperfect, correlation between a drug’s lipophilicity and its colonic absorptivity. Accordingly, we cannot perceive clear error in the district court’s factual findings that while colonic absorption was not guaranteed, the evidence, viewed as a whole, is clear and convincing that a person of ordinary skill in the art would nonetheless have perceived a reasonable likelihood of success and that she would have been motivated to combine prior art references to make the claimed invention.

…

Likewise, we find no error in the district court’s consideration of secondary indicia of obviousness. We therefore affirm its legal conclusion of obviousness, finding the district court to have correctly held that Mylan met its burden of overcoming the presumption of validity that attaches to an issued patent.

See also Alza v. Impax (Fed. Cir. 2006, 06–1047)

A jury unanimously found that Abbott Laboratories willfully infringed Innogenetics’ U.S. Patent No. 5,846,704, which covers a method of genotyping the Hepatitis C Virus (“HCV”) using probes targeting sequences from the 5′ untranslated region of HCV.

Hepatitis C viruses (HCV) are a family of positive-stranded, enveloped RNA viruses causing the majority of non-A, non-B (NANB) hepatitis. The ‘704 patent claims:

1. A method of genotyping HCV present in a biological sample comprising hybridizing nucleic acids in a biological sample with at least one probe and detecting a complex as formed with said probe and said nucleic acids of HCV, using a probe that specifically hybridizes to the domain extending from the nucleotides at positions -291 to -66 of the 5′ untranslated region of HCV.

The U.S. District Court judge still has the discretion to up the award to triple the amount – so-called treble damages (35 U.S.C. § 284) – since the jury specifically determined Abbott’s patent infringement was willful. Innogenetics also has said it will seek an injunction against Abbott diagnostic products that infringe its ‘704 patent and any other available remedies.

On September 2, 2006, a jury returned a unanimous verdict for Innogenetics that the ‘704 patent was valid and has now determine damages and whether the infringement had been willful. Upon a finding of infringement, a court may increase damages, but a finding of increased damages is not mandatory. Under the statute, a court “may increase the damages up to three times the amount found or assessed.” Further, a court may award attorney’s fees as well. However, willful infringement is merely a predicate act to the enhancement of damages as a finding of willful infringement, though a sufficient basis for an award of increased damages does not mandate them.

Whether a finding of willful infringement is warranted depends on what the Federal Circuit has characterized as “the totality of the circumstances” presented, namely, whether a reasonable person would prudently conduct himself with any confidence that a court might hold the patent invalid, not infringed or unenforceable.

One factor is whether the infringer has obtained an opinion of counsel regarding infringement and/or validity. The Federal Circuit has held that once a party has actual notice of another’s patent right, that party has an affirmative duty to respect those rights, and that this affirmative duty normally entails obtaining advice of legal counsel.

The Boston Globe ran an article about Ohio Governor Bob Taft traveling to Boston looking to attract a few more companies — or at least their new or expanded facilities — for Ohio. On the heels of the recent acquisitions by Cincinnati’s Procter & Gamble Co. and Federated Department Stores of Boston’s Gillette Co. and Filene’s respectively, Taft is paying a visit to biotechnology firms Genzyme Corp. and Alkermes Inc., as well as CME Energy. Massachusetts is the fourth state to which Taft has made recruiting trips in the last year.

There is fierce competition for jobs and many states covet high-tech industries with their higher paying salaries (read: more tax dollars for the state). Ohio is still down 180,000 jobs from its prerecession peak, a 3 percent decline, so efforts are being put into grabbing action from outside the state. Ohio’s not alone, though. Ohio is now putting out a nationwide marketing effort to promote a recent tax overhaul that reduces corporate taxes and the state is spending nearly $500,000 to advertise its business-friendly policies in the Wall Street Journal.

Meanwhile, Taft and lieutenant governor Bruce Johnson have visited about a half dozen states to conduct what they call “domestic trade missions.” Like many states, Ohio wants to expand its biotechnology and medical sciences sector but they’re up against a lot of competition. According to a 2004 report from the Biotechnology Industry Organization (BIO), 40 states have specifically targeted the biosciences in their economic-development efforts, hoping to bring more high-paying jobs to their communities. All this adds up to a lot of states spending like a drunken sailor on incentives to attract jobs. The average size of incentive packages is estimated at $10,000 per employee although, in 1993, Alabama paid Mercedes Benz an eye-popping $150,000 per job created.

Even though some question if this $50 billion a year subsidy game is worthwhile, it hasn’t slowed the action. See some efforts:

Wisconsin

Georgia

Washington

Tennessee

Texas