FTC probes Mylan about settlement with Cephalon over modafinil

Cephalon Inc. (CEPH) entered an agreement related to patent-infringement litigation with Mylan Laboratories, granting Mylan Laboratories non-exclusive, royalty-bearing rights to market and sell modafinil in the U.S.

Cephalon also entered separate agreements with Teva Pharmaceuticals USA Inc. (TEVA), Ranbaxy Pharmaceuticals Inc. and Barr Laboratories Inc. (BRL).

According to Mylan Laboratories' quarterly report filed Friday with the Securities and Exchange Commission, the FTC requested information from the company and certain subsidiaries related to the patent litigation and settlement with Cephalon in a letter dated July 11. Mylan Laboratories said that beginning in April, it and four other drug manufacturers were also named in a series of civil lawsuits tied to the modafinil patent-litigation settlement agreements.

St. Jude settles patent cases with Boston Scientific

St. Jude is no stranger to patent cases. On July 31, St. Jude settled 4 cases and limited two more.

Medical device makers St. Jude Medical Inc. and Boston Scientific Corp. said on July 31 the have settled four patent litigation matters.

Under the settlement, the two companies also agreed to limit how two other unresolved cases will be pursued.

The two companies have also agreed to a patent cross license involving their cardiac rhythm management patent portfolios and a separate cross license of some other patents. [Reuters]

EchoStar and DirecTV planning to merge?

from the Denver Post of July 31: When EchoStar Communications Corp. and DirecTV head to a Federal Communications Commission auction Aug. 9, they're not simply bidding on wireless airwaves but for survival in a broadband world. The satellite TV companies have teamed up under the name Wireless DBS LLC to bid on licenses for Advanced Wireless Services spectrum.

It could also be part of a courtship leading to a merger between EchoStar, based in Douglas County, and DirecTV, based in El Segundo, Calif. Rupert Murdoch's News Corp. controls DirecTV.

In April 2006, Thomas Hawk wrote of the TiVo patent victory against EchoStar:

In what I described as a win-win for DirecTV and TiVo, earlier this week TiVo and DirecTV renewed their service and support agreement which contained an important provision allowing DirecTV to avoid being sued by TiVo for the next three years.

From the Los Angeles Times: ""If you're going to defend your patents and try to license it, this kind of win certainly makes those negotiations easier," said Larry Gerbrandt, senior vice president and general manager of Nielsen Analytics, which specializes in emerging media technology.

The verdict sent TiVo's shares up 22% to $9.80 in after-hours trading, after falling 7 cents to $8.05 in regular trading. EchoStar's shares closed up 12 cents at $29.97 during regular trading. They were little changed in late trading."

EchoStar of course will appeal this verdict but it's impact is largely more that it gives TiVo an incredibly strong hand to negotiate with other providers looking to avoid a suit similar to EchoStars.


from an EchoStar case, 448 F.3d at 1302

EchoStar contends that waiver of opinions does not extend to advice and work product given after litigation began. While this may be true when the work product is never communicated to the client, it is not the case when the advice is relevant to ongoing willful infringement, so long as that ongoing infringement is at issue in the litigation. See Akeva LLC, 243 F.Supp.2d at 423 (”[O]nce a party asserts the defense of advice of counsel, this opens to inspection the advice received during the entire course of the alleged infringement.”); see also Crystal Semiconductor Corp. v. TriTech Microelectronics Int’l, Inc., 246 F.3d 1336, 1351-1353 (Fed. Cir. 2001) (noting that an infringer may continue its infringement after notification of the patent by filing suit and that the infringer has a duty of due care to avoid infringement after such notification).

[work product privilege]

Also, see later case Informatica v. BODI, 2006 WL 2038461, citing to EchoStar.

***
See also EchoStar v. Finisar.

More rhetoric in the WARF v. CIRM battle over stem cell patents

Terri Somers in the Union-Tribune: In Wisconsin lurks a force that scientists say is strangling embryonic stem cell research far more than any federal funding restrictions.

Scientists charge that WARF's greed in controlling the patents is thwarting potentially life-saving research. [IPBiz: note that TIME magazine did NOT include this issue in its July 30 coverage. The first two WARF patents are US 5,843,780 and 6,200,806.]

As a result, many U.S.-based scientists are looking for opportunities to take their work abroad. Two studies out of Princeton University show that U.S. stem cell scientists, compared to researchers in other fields, are disproportionately considering leaving the country. Patent concerns and access to the essential cells were among the reasons cited. [IPBiz note: the Princeton study showed stem cell scientists got more offers than other biologists, but did not comment on how they were considering the offers.]

Under the [WARF] patents, a researcher in the United States who uses embryonic stem cells in any way must pay a licensing fee to WARF, the university's licensing arm. [IPBiz: what happened to 35 USC 271(e)(1) and Merck v. Integra?]

“Outside of the (U.S.) government, the No. 1 hindrance to stem cell research is the WARF patents because of how they try to enforce their licenses,” said Mahendra Rao, the former head of the National Institutes of Health's stem cell efforts. [IPBiz: it looks like Rao places the Bush funding policy as the most significant problem, in contrast to Loring.]

Rao quit that coveted position last year and took a job with Carlsbad-based Invitrogen, an international biotechnology company. In his new job, Rao can work on embryonic stem cell projects at Invitrogen's offices around the globe. That includes an office in Asia, where the company recently moved a portion of its embryonic stem cell program, said company spokesman Greg Geissman. [IPBiz: moving the location of one's research does not avoid the problem of infringement when the product is brought into the U.S.]

Rao's concern about WARF has been echoed by the current stem cell chief at the NIH and by the chief scientific officer at the science-funding Juvenile Diabetes Research Foundation and intellectual property lawyers across the country.

The critics say they don't oppose patents, just the degree to which the foundation wants to profit from those it controls. [IPBiz: disputes about the AMOUNT of patent royalties are well-known. See the Wright Brothers.]

“If a company can't afford our $25,000 yearly fee, then it cannot afford the growth factors it needs to grow the cells,” Donley said.

That's a flawed argument, said Cathryn Campbell, an intellectual property lawyer with Needle and Rosenberg in San Diego.

“It's about how to maximize the value of this technology and how much this license should cost,” Campbell said. “Even $25,000 is a lot for the kind of biotech company that will likely be doing this research.”

Reach-through royalty issue -->

“We are not opposed to patents. We respect them and see their value,” Goswami said. The company typically pays for licenses on 40 patents a year, he said.

But WARF has what he called “a reach-through royalty clause, where they say anything you've invented remotely by using human embryonic stem cells will now have a royalty obligation back to WARF.”

For example, if Invitrogen uses embryonic stem cells early in the development of a tool for drug discovery but the production of the tool doesn't involve stem cells, WARF would still want royalties on the tool, he said.

WARF also wants companies with licenses to pay royalties on products they sell in foreign markets that don't honor the patents, Goswami said. That would give an advantage to companies overseas, which can develop the same tools without owing money to WARF.

Royalties under Proposition 71:

Recently, the California institute's [CIRM's] board decided that if a grant-receiving organization made a discovery with Proposition 71 dollars that could be patented and sold, a portion of the profits would be returned to the taxpayers.

The board debated this policy at length, because it was looking for a balance between getting a return on the investment of taxpayers and not hindering scientific development.

WARF has decided it is entitled to a cut of the state's royalties.

*****

An editorial from the Wisconsin State Journal on July 29, 2006 entitled Dear California: Nuts to you!:

To hear the folks in California tell it, the single biggest roadblock to the development of life-saving medical treatments based on stem-cell science is -- Wisconsin.

But the California group has not stopped there [re-exam request of PubPat and FTCR]. It has also launched an attack against WARF in the court of public opinion, charging that:

"The folks in Wisconsin need to get the dollar signs out of their eyes and stop impeding vital research."

Furthermore, the group has tried to discredit Thomson, claiming that his discoveries were so "obvious" that he did not deserve any patents.

Well. Those are some serious grievances.

The Patent Office will deal with the legal merits of the Californians' complaint. But how should Wisconsin respond to the more personal attacks on its university and its star scientist? [IPBiz: this is sounding like the initial defense of Hwang Woo-Suk in South Korea.]

Let's begin with: What a load of bunk!

Attempting to discredit Thomson is like saddling up a mouse for a cross-country ride: You're not going to get far.

Thomson earned his patents by directing the first group of scientists to isolate human embryonic stem cells and keep them alive in an unchanged state. His achievement was widely praised as the breakthrough that created the possibility of using embryonic stem cells to treat disease and save lives.

Time magazine put Thomson on its cover in 2001 with the caption "the man who brought you stem cells," and in the article inside the magazine asked "Who says there are no Einsteins anymore?"

The conflict with the California group occurred only because California wants to use WARF's patented discoveries not only for research but also for commercial development.

California has a state plan to invest $3 billion in embryonic stem-cell research. As part of that plan, the California Institute for Regenerative Medicine wants to use Wisconsin's patented stem cell lines and methodology -- for free -- to create commercial developments, which the institute expects to patent, earning money from royalties and fees.

Follow the California logic: Wisconsin should be prohibited from making money from its patents, but California should be allowed to use the Wisconsin stem cells and methods to get its own patents, from which it will make money.

It's sort of like playing basketball against a team that declares: Our baskets count; yours don't.

Patent disputes are common and often resolved through negotiation. It would be a good idea in this case for California to come to the bargaining table with a reasonable offer to pay up for Wisconsin's patented stem cells and methods.

It would also be a good idea for the Californians to drop the anti-Wisconsin rhetoric. The facts are on our side.

Lots of stem cell coverage on July 30

Probably in anticipation of the five year anniversary of the Bush funding restrictions, many news groups have articles on stem cells.

Time's (electronic) cover story for July 30 is "Stem Cells: the hope and the hype," with a teaser: "The debate is so politically loaded that it's tough to tell who's being straight about the real areas of progress and how breakthroughs can be achieved. TIME sorts it out."

Time's article is interesting for what it does, and does NOT, cover. TIME mentions the restrictions on federal funding for embryonic stem cell research of President Bush in August 2001 and TIME discusses present implications of this restriction. TIME does not mention at all the patent issues, as for example with the WARF / Thomson patents (e.g., 5,843,780 and 6,200,806), which some people think are more significant barriers to stem cell research. The TIME article does not mention Hwang Woo-Suk by name, but obliquely refers to the fraud in a discussion of therapeutic cloning. TIME does not mention the tremendous gap between what scientists were willing to believe about Hwang's work and the reality of "how far back" the state of the art is in SCNT. TIME does not succeed in presenting all the issues, much less in sorting them out.

The TIME article presents the hope vs. hype theme:

It is the nature of science to mix hope with hedging. It is the nature of politics to overpromise and mop up later. But the politics of stem-cell science is different. Opponents of ESC research—starting with Bush—argue that you can't destroy life in order to save it; supporters argue that an eight-cell embryo doesn't count as a human life in the first place—not when compared with the life it could help save. Opponents say the promise of embryo research has been oversold, and they point to the cures that have been derived from adult stem cells from bone marrow and umbilical cords; supporters retort that adult stem cells are still of limited use, and to fully realize their potential we would need to know more about how they operate—which we can learn only from studying leftover fertility-clinic embryos that would otherwise be thrown away.

The "exodus of US scientists" issue is present:

States from Connecticut to California have tried to step in with enough funding to keep the labs going and slow the exodus of U.S. talent to countries like Singapore, Britain and Taiwan. Meanwhile, private biotech firms and research universities with other sources of funding are free to create and destroy as many embryos as they like, because they operate outside the regulations that follow public funds.

Not mentioning the Hwang scandal, TIME neglects to point out that part of the fraud originated in the desire of a junior Korean researcher to work in the United States.

Of the approved embyronic stem cell lines:

For scientists who choose to work with the approved "presidential" lines, the funding comes wrapped in frustration. Today there are only 21 viable lines, which limits genetic diversity. They are old, so they don't grow very well, and were cultured using methods that are outdated. What's more, the chromosomes undergo subtle changes over time, compromising the cells' ability to remain "normal." The presidential lines, scientists say, are wasting money as well as time. Larry Goldstein's lab at the University of California at San Diego is a life-size game of connect the dots. Each machine, cell dish, chemical and pretty much every major tool bears a colored dot, signaling to lab workers whether they can use the item for experiments that the government won't pay for.

"Not all embryonic-stem-cell lines are created equal," says Dr. Arnold Kriegstein, who runs the Institute for Regeneration Medicine at the University of California, San Francisco. "Some are more readily driven down a certain lineage, such as heart cells, while others more easily become nerve. We don't understand how it happens, but it does mean we need diversity."

Therapeutic cloning and SCNT are discussed:

The only people who claim to have succeeded in creating human-stem-cell lines through nuclear transfer were the South Korean researchers who turned out to be frauds [i.e., Hwang Woo-Suk] It will take much trial and error to master the process, but where do you get the human eggs needed for each attempt, particularly since researchers find it ethically inappropriate to reimburse donors for anything but expenses? And even if the technique for cloning embryos could be perfected, would Congress allow it to go on?

The TIME article discusses alternatives:

To get around political roadblocks, scientists are searching for another source of cells that is less ethically troublesome, ideally one that involves no embryo destruction at all. One approach is "altered nuclear transfer," in which a gene, known as cdx2, would be removed before the cell is fused with the egg. That would ensure that the embryo lives only long enough to produce stem cells and then dies. That strategy, promoted by Dr. William Hurlbut, a member of the President's Council on Bioethics, has its critics. Dr. Robert Lanza of biotech firm Advanced Cell Technology considers it unethical to deliberately create a crippled human embryo "not for a scientific or medical reason, but purely to address a religious issue." The most exciting new possibility doesn't go near embryos at all. Dr. Shinya Yamanaka of Kyoto University reported tantalizing success in taking an adult skin cell, exposing it to four growth factors in a petri dish and transforming it into an embryo-like entity that could produce stem cells—potentially sidestepping the entire debate over means and ends.

Lanza's group is also close to filing for fda permission to begin clinical trials on three cell-based therapies: one for macular degeneration, one for repairing heart muscle and another for regenerating damaged skin. Not to to be outdone, the academic groups are just a few steps behind. Lorenz Studer at Memorial Sloan-Kettering Cancer Center in New York City has been able to differentiate ESCs into just about every cell type affected by Parkinson's disease and has transplanted them into rats and improved their mobility. Next, he plans to inject the cells into monkeys.

The TIME article discusses cord blood cells:

While not as flexible as embryonic cells, cord and placental cells have proved more valuable than scientists initially hoped. Although about 90% of cord-blood stem cells are precursors for blood and immune cells, the remaining 10% give rise to liver, heart-muscle and brain cells and more. Over the past five years, cord-blood transplants have become an increasingly popular alternative to bone-marrow transplants for blood disorders, particularly when a bone-marrow match can't be found.

Of a "Manhattan-like" project:

Owen Witte of UCLA: "I hate to say it, but biology is more complicated than splitting the atom. The physicists on the Manhattan Project knew what they needed to accomplish and how to measure it. In biology, we're codeveloping our measurement tools and our outcome tools at the same time."


View the TIME article here.

***
The Fond du Lac Reporter noted:

Scientists fret that the United States will now fall even farther behind the pace of the rest of the world when it comes to stem cell research. According to Medpage Today, in 2002, about a third of the 10 published articles involving human embryonic stem cells were from U.S. research groups. Two years later, U.S. groups accounted for only one-quarter of the 77 publications.

"Anytime we are limiting research, we are putting our country at risk when we know our competitors are doing the same kind of research," said Fond du Lac's John Whitsett, president of the National Science Teachers Association.

Of Wisconsin's involvement in stem cell research:

The discovery was pioneered and continues to be nurtured at the University of Wisconsin-Madison.

One assumes that Jeanne Loring, PubPat, and FTCR would dispute the comment about nurturing.

**
The LaCrosse Tribune had a comment: Stem cells: the temptation in the laboratory.

**
Bloomberg reports on Tony Blair visiting the US concerning stem cell research:

British Prime Minister Tony Blair will meet executives from Californian biotechnology companies including Genentech Inc., StemCells Inc. and Gilead Sciences Inc., seeking to bolster stem-cell research back home. The Prime Minister is on a four-day trip to California aimed at increasing cooperation ``between the increasingly high-tech'' economies of the U.S. state and Britain. The government has doubled the amount it is spending on stem-cell research to 100 million pounds ($186 million) over the next two years.


***
LA Times on July 30:

Q: What's the California situation on stem cells?



A: In November 2004, 59% of California voters approved Proposition 71, paving the way for the state to provide $3 billion over 10 years to stem cell research. Connecticut, Illinois, Maryland and New Jersey have also approved state funds to fill in the gap left by the lack of federal funding.

Several groups have challenged the constitutionality of Proposition 71 and are appealing an April state Superior Court decision that upheld the proposition.

The legal wrangling has prevented the use of any Proposition 71 money for research. To get the California Institute for Regenerative Medicine off the ground, the state is selling bonds to philanthropists, and the governor lent $150 million from the general fund.

Q: Why is the restriction on federal funding a big deal?

A: Universities depend on federal funding for about 60% of their research budgets. Without this money, scientists must rely on private and state funds to advance their stem cell research.

Many scientists think the number of embryonic stem cell lines eligible for federal funding is too small. When the president announced his stem cell policy in 2001, 78 lines were thought to be available. The number is about 20 now because the rest are unavailable or not research-quality.

Additionally, the remaining cell lines were grown in the presence of mouse cells to help nourish them and get them to stick to the petri dish. This makes them unsuitable for transplanting into humans. Scientists want to make new stem cell lines now that they know how to grow them without mouse cells.

See LATimes, Funding Restrictions at Heart of Legal Wrangling

http://www.latimes.com/news/nationworld/nation/la-sci-stemcellqampa3

NYTimes on Intel's Core 2 Duo

The write-up by the New York Times contained the sentence: The Core 2 Duo, Intel says, can deliver as much as 40 percent better performance while using as much as 40 percent less power and giving off less heat.

The Times also noted:

The chief executive of Intel, Paul S. Otellini, told an audience gathered at the company’s headquarters here that the chips represented the most significant advancement in computer chip design and performance since the Pentium processor in 1993.

and

The Core 2 Duo also arrives just as Intel is completing a review of its operations in hopes of becoming more efficient. Mr. Otellini declined to reveal whether the company, which earlier this month announced it would lay off 1,000 managers, would have additional job cuts.

***
Rupert Goodwins of ZDNet gives more details:

It is hard to overstate the importance of the Core micro-architecture to Intel, and thus to the rest of the industry. The product of a major debate within Intel (what Pat Gelsinger, General Manager of the Digital Enterprise Group, called the 'speed freaks versus brainiacs'), it marks the victory of those who felt that extra performance was best achieved not by constantly upping the processor's clock speed, but by going for ever more parallel systems with much finer control of performance versus power consumption.

(...)

All of the above is true separately for each core, each of which operates entirely independently of the other. They share their Level 2 cache, though, and this is where Intel has optimised operations for the simultaneous use of both cores. This means that when both cores are operating on the same area of memory, just one copy of the data is needed in the cache, increasing efficiency and leaving more cache for other processes. The cache also dynamically allocates how much is used by each core, so that if one is idle or operating in a slow, low-power mode, more cache is available to the other.


(...)

Underlying all this is Intel's dynamic power management. Areas of the chip that aren't needed at any particular point can be disconnected from main power, while others are switched into low-power modes when they don't need to deliver full performance. This extends to buses, which can be split so that parts not needed are powered down without affecting the rest, and the cache, which puts parts of itself into low-power modes that maintain their contents but react only sluggishly when this wouldn't affect performance.

More on the WARF / CIRM conflict in research in embryonic stem cells

In the current patent discussion/controversy between a holder of patents on embryonic stem cells (Wisconsin's WARF) and a potential user/"infringer" of said patents (California's CIRM), we are seeing that patent conflicts can reach entities that are nominally research institutions, but which nevertheless are planning commercializations.

Although the Supreme Court case of "Merck v. Integra" appeared to be one between two commercial entities, the underlying conflict came through one research entity (Scripps) wanting to use a patent created by another research entity (Burnham), after one research entity (Scripps) had made a deal with a commercial entity (Merck KGaA).

In the Merck v. Integra case, the Supreme Court stated that it had not understood the CAFC to have made a clinical/preclinical distinction as to the scope of the research exemption of 35 USC 271(e)(1) [meaning that "preclinical" activities could be insulated from infringement]. The common law research exemption was not reached and the "research tool" issue was not reached, one way or another.

Jeanne Loring and Cathryn Campbell wrote an article entitled "Intellectual Property and Human Embryonic Stem Cell Research," which appeared in 311 Science 1716 on March 24, 2006, which article did not mention either 35 USC 271(e)(1) or Merck v. Integra. The research exemption of 35 USC 271(e)(1) is of relevance to protecting researchers in the stem cell area from patent infringement actions. Cathyrn Campbell was familiar with the Merck v. Integra case in 2006, having been aligned with the position of patentee. Nevertheless, the March 2006 article suggests that patentee WARF presents a greater danger to stem cell research than does the research funding limitations of George Bush of August 2001.


from "Voices of San Diego":

Ms. Campbell and Ms. Eastham Go to Washington

By CATHRYN CAMPBELL and KARIN EASTHAM
Contributing Voices
Published April 22, 2005

A number of San Diegans, including the authors, converged on the U.S. Capitol to attend the Supreme Court hearings yesterday in a case that has deep San Diego roots-- and potentially broad implications for many local sectors of the life science industry. How did we find ourselves there, Karin in a reserved front-row seat, Cathryn at counsel table?

For both, it was an awe-inspiring, not-to-be forgotten opportunity to witness first hand that august body, which for everyone but the two of us will doubtless remain better known for Roe v. Wade than it will be for Merck KGaA v. Integra Lifesciences I, Ltd. Cathryn has a long history with this case and the patents at issue here, having prosecuted them on behalf of the Burnham Institute since the 1980s. Karin was an invited guest as a representative of the Burnham Institute and stood in for Erkki Ruoslahti, who was in Japan to formally accept the prestigious Japan prize for his seminal work in cell adhesion, the very technology that is the subject of this case.

Stemming from a patent infringement suit filed in San Diego in 1994, the dispute involves pioneering cell biology discoveries in the early 1980s at the Burnham Institute by Drs. Erkki Ruoslahti and Michael D. Pierschbacher. Merck KGaA (the German drug-maker, not to be confused with the U.S. company of the same name) sponsored research at the Scripps Research Insitute to support research on a potential anti-cancer compound which infringed The Burnham's patents.

When Merck declined to take a license from the Burnham Institute, a suit for infringement was filed naming Merck KGaA, Scripps and its researcher, Dr. David Cheresh, as defendants. Scripps and Dr. Cheresh were later dismissed as parties. After a 25-day trial in the local District Court, the jury found that Merck had willfully infringed. Yesterday-nine years after its filing-the case was before the U.S. Supreme Court, the only patent matter to be heard this year by our nation's highest court. And the issues at stake go far beyond the issue of patent infringement.

Mauricio Flores, a partner at McDermott Will & Emery LLP (and Cathryn's law partner), presented arguments to the court on behalf of Integra in a case that has broad implications to various constituencies in the life sciences sector: research institutions, biotechnology companies, research tool companies, and pharmaceutical companies. The fundamental question is whether Merck, through research performed at the Scripps Research Institute, infringed Burnham patents held by Integra. Merck claims that the work performed at Scripps qualified for a Food and Drug Administration exemption.

Lawyers for each side are allotted 30 minutes including questions from the justices. What surprised us was the large number of questions and interruptions. The justices seemed intent and anxious on getting answers to their specific issues. At times, the proceedings seemed more like a conversation than a Perry Mason trial. The time restriction is strictly adhered to, and when the red light comes on, the lawyer says, "Thank you" and immediately stops.

The Congressional exemption provides that a drug manufacturer can use an invention without obtaining a license when the manufacturer can prove that its otherwise infringing uses were "solely for uses reasonably related to the development and submission of information" for FDA submissions. Integra believes the Scripps work infringed of these patents because it was basic biomedical research to identify drug candidates; the work related to FDA requirements was performed at Merck in Germany, using the Good Laboratory Practices required by the FDA.

However, the industry wide implications are of broader importance than the outcome between the two parties in this case. The fundamental questions that could be addressed by the Supreme Court are the following:

Q1. Is any preclinical research potentially eligible for the FDA exemption or will a line be drawn between preclinical and clinical testing for purposes of the exemption?

Q2. Will the Supreme Court use this case to reconsider the common law research exemption to protect basic biomedical research?

Q3. Will the FDA Exemption be held to be broad in scope that "research tool" companies are at risk of losing patent protection when their technologies are used for generation of FDA data?

Q4. Is the FDA exemption only applicable to generics? What about medical device companies?

Based upon our observations of the probing and intense questions asked by the justices during the arguments by the lawyers on both sides, we have made some predictions regarding the decision, which is expected this summer:

Prediction 1. Clearly, work on human clinical subjects is exempt from patent infringement. However, scientists and drug innovators need some clearer guidelines as to whether basic biomedical research infringes patents, but no bright lines are expected to be drawn by the court between preclinical and clinical testing. Instead, it is expected that the Court will indicate that some preclinical work on animals or in test tubes is eligible for the FDA exemption, but decisions will be based upon the unique facts in each case.

Prediction 2. The common law research exemption was not at issue in this case and it is unlikely that the Court will address this.

Prediction 3. The Court is likely to consider that this case does not raise the issue of tool patents, and thus companies like San Diego's Invitrogen will still be able to go after infringers using their patented technology in basic research.

Prediction 4. The Court has previously held that the FDA exemption is not limited to protecting generics companies and applies to drug and device manufacturers.

While the Justices provided us with multiple clues about the potential industry-wide conclusions in this case, no case-specific leanings could be inferred from the intense line of questioning. We will have to wait patiently as this case approaches its 10th birthday. We will also wait patiently to learn whether our predictions accurately capture the outcomes that have landmark implications for our San Diego life sciences industry.

Cathryn Campbell, an attorney specializing in intellectual property, has focused her practice on the biotechnology industry since its infancy in the early '80s. She is a partner in the law firm of McDermott Will & Emery LLP.

Karin Eastham, executive vice president and chief operating officer of the Burnham Institute, has over 25 years experience in financial and operations management, primarily in life sciences companies. Karin also serves as a director on several biotechnology companies, public and private, and is on the board of UCSD Athena.

Batteries aren't getting better, so Intel touts lower power consumption

SF Chron: Intel Corp. introduced its newest, fastest and most energy-efficient microprocessors July 27 in a gala event that signaled its determination to stem the inroads of rival Advanced Micro Devices. Intel's new microprocessors, which it calls Core 2 Duos, are designed to offer higher performance and lower power consumption -- a feature that is increasingly important in extending the battery life of laptops.

(...)

To get better performance at lower power consumption, Intel based the Core 2 Duo on a pair of relatively simple principles that mask a lot of engineering.

The first is the adage that two heads are better than one. Intel put two processors, side-by-side, inside a single chip and divided the computational workload between them, David Tuhy of Intel said.

To reduce power consumption, Intel relied on the slow-and-steady principle -- making a fundamental tweak to the transistors inside the chip.

Transistors are the basic unit of any chip. Imagine them as gates that swing open and shut, allowing electricity to pass through. These opening and shutting gates create the zeroes and ones that comprise the language of computer programs.

In the past, engineers sped up the rate at which these gates opened and shut, Tuhy said. That improved performance but took more power. In the Core 2 Duo, Intel slowed down this rate, opening the gates less frequently, but put many transistors into the chip -- roughly 291 million -- to create faster computation with less power.

***

Now, does Intel have patent protection based on the implementation of these two principles? Is AMD left in the dust?

Owen Wilson responds on Dupree knock-off charges by Steely Dan

USAToday: In a statement released by his spokeswoman, Ina Treciokas, [Owen] Wilson said: "I have never heard the song 'Cousin Dupree' and I don't even know who this gentleman, Mr. Steely Dan, is. I hope this helps to clear things up and I can get back to concentrating on my new movie, HEY 19. "

This episode looks more like a publicity stunt than an intellectual property event. One does note that, in copyright but NOT patent, "independent creation" is a defense. But it's hard to believe that Owen Wilson never heard of Steely Dan, so this looks like mutual backscratching more than a lawsuit in the making.

Bob Park talks about "Bleep"

Following last week's discussion about Adam Dreamhealer, Bob Park talked a little about "Bleep."

In October 2005, there was a conference in Scottsdale to discuss the movie What The Bleep Do We Know? in terms of mystery, possibility, and change. An ad said: Learn what cutting-edge physicists know about the true nature of reality, and what it means for you.

One of the speakers was WILLIAM TILLER, PH.D., a fellow to the American Academy for the Advancement of Science [AAAS], Professor Emeritus of Stanford University's Department of Materials Science, and founding director of the Academy of Parapsychology and Medicine and The Institute of Noetic Sciences.

Park promises more.

A separate blog entry in July 2006 notes:

Next month, Adam [Dreamhealer] is to appear with some of the film's scientific personalities at Simon Fraser University for a What the Bleep Do We Know? (when it comes to money he needs less privacy).

Microsoft infringes through distribution of master outside of US

Microsoft Corp. infringed an AT&T Corp. patent for speech-coding technology in its distribution of a master version of the Windows operating system outside of the U.S. for replication abroad, the U.S. Court of Appeals for the Federal Circuit ruled Wednesday, July 26, concluding the final issue remaining from a 2001 lawsuit.

This is a significant decision in establishing the reach of US patent law.

Mosaid sues Micron in ED Texas

A complaint by Mosaid against Micron, the biggest U.S. maker of memory chips, was filed July 27 in federal court in Marshall, Texas. Also sued were Powerchip Semiconductor Corp., Taiwan's largest memory-chip maker, and ProMOS Technologies, the country's third-largest. The suit came a day after Micron sued to challenge 14 patents owned by Mosaid for dynamic random access memory chips, or DRAM.

Separately, MOSAID Technologies Incorporated announced on July 27 that it has filed a motion to dismiss Micron Technology, Inc.'s Complaint for Declaratory Judgment, which was filed in the U.S. District Court, Northern District of California, San Jose Division on July 24, 2006, or in the alternative, to transfer the case
to the District Court for the Eastern District of Texas, Marshall
Division, where MOSAID's recently filed case against Micron and other
defendants is pending.

Business is booming in ED Texas. A new website (www.MarshallOfficeSpace.com) is focusing on providing services and products to attorneys visiting Marshall, Texas while involved in IP litigation cases at the federal courthouse.

The Mosaid/Micron sequence illustrates the competitive filings of infringement and declaratory judgment (DJ) actions.

"Traditional foreign wisdom" to be invoked in mangosteen case

Thailand will submit information on mangosteen to the United States Patent and Trademark Office (USPTO) to try to stop an American food company from taking out patents based on the popular fruit. US-based Nature's Sunshine Products, a producer of herbal and food supplements, applied for patents for drinks made from mangosteen extracts on Oct 27, 2004. According to Kanissorn Navanugraha, the director-general of the Intellectual Property Department, extracting mangosteen for beverages was part of Thai traditional wisdom. "I will submit to the US authorities that Thais have been using traditional knowledge to derive extracts from mangosteen for a long time," he said.

This reminds one of the controversies surrounding the neem plant. One also thinks of the use of a book by "beat generation" poet Ginsburg as prior art in a certain plant patent case.

Toshiba to pay Masuoka over flash memory invention

In a deal reached at the Tokyo District Court, Toshiba agreed to pay $750,000 to Fujio Masuoka, a former Toshiba employee and now a professor at Tohoku University, concerning the invention of a flash memory chip.

The case highlights a shift in which more Japanese workers are demanding compensation for individual talent and personal contributions in a corporate culture that still largely expects employees to toil for the good of the company. One recalls the earlier blue light emitting diode case, involving Nakamura and Nichia.

Kazaa settles copyright case for $115 million

Further to the Supreme Court decision in Grokster, one notes that Kazaa has settled:

Sharman Networks Ltd.'s Kazaa, a file-sharing service that helped introduce millions to online music theft, has agreed to settle litigation with the entertainment industry for more than $115 million. The settlement represents the waning of the era of Internet businesses facilitating unauthorized music downloading. (from the Wall Street Journal through MoneyWeb.

The article also states:

Napster, created in 1999, was the first file-sharing service that became popular for illegally downloading music. After it was shut down, Kazaa, StreamCast Networks Inc.'s Morpheus, and Grokster took off. After lawsuits from the record industry [RIAA], Napster shut down and the name now belongs to a legitimate music download service. Grokster was purchased last year by Mashboxx, which expects to launch a legitimate file-sharing music service later this year.

Kazaa was created by Janus Friis and Niklas Zennstrom in 2000. The two avoided travel to the U.S. since 2001 because they feared being served legal papers, a worry that ends with the settlement. Under the terms of the settlement, Kazaa agreed to introduce filtering systems to ensure that people can no longer use Kazaa to pilfer copyrighted music and movie files. Sharman, based in the Pacific Island nation of Vanuatu, also said it would work with the entertainment companies to sell licensed content. After the Kazaa sale to Sharman, Mr. Friis and Mr. Zennstrom founded Internet phone service Skype, which is based on the same underlying technology as Kazaa. Last year, they sold Skype to eBay Inc. for about $2.6 billion in cash and stock.

Of the Grokster case defendants, Grokster agreed to settle that case for $50 million and promised to go legitimate, and now Kazaa has settled. StreamCast's Morpheus is the sole remaining defendant in the case pending in federal court in Los Angeles. Although the Supreme Court decision was criticized as not going far enough, it seems to have produced results.

DOJ looking into BMS deal with Apotex on PLAVIX

Further to an earlier report on IPBiz, the DOJ is looking into the BMS deal with Apotex on PLAVIX.

According to Bloomberg, BMS and Aventis learned July 26 of an investigation by the Justice Department's antitrust division, according to similar statements today. Bristol-Myers and Sanofi agreed to pay generic- drug maker Apotex Inc. an unspecified amount to stay off the market with a generic copy of Plavix until 2011.

Only Pfizer Inc.'s Lipitor cholesterol pill had higher sales than Plavix last year, with $12.2 billion.

Other companies also are vying to sell a generic version of the drug, a $4-a-day pill that prevents the formation of blood clots for patients having a heart attack or undergoing artery- clearing procedures. They include including Dr. Reddy's Laboratories Ltd. of Indian and Israel's Teva Pharmaceutical Industries Ltd., the world's biggest maker of generic drugs. Those cases are pending.

State funding of embryonic stem cell research

Richard Guerra, States Take the Initiative to Regulate And Resolve the Stem
Cell Debate, 7 Fl. Coastal L. Rev. 35 (2005)

the legislature's best approach is to permit the industry to grow
with a minimal amount of regulation and allow semi-theoretical
controversies, such as the stem cell debate, to fall into the hands of an able
judiciary. Otherwise, if the Florida legislature feels compelled to regulate
embryonic stem cell research, the likely result of such regulation will be to
discourage the propagation of one the most promising and lucrative industries known to date.

Wesley J. Smith, INVESTIGATING THE LEGAL AND ETHICAL DILEMMAS OF
MODERN BIOTECHNOLOGY: THERAPEUTIC CLONING: IT'S ABOUT MUCH MORE THAN
EMBRYONIC STEM CELL RESEARCH, 20 St. John's J.L. Comm. 29

Recall that this controversy started with the argument that, "All we want to use are
leftover embryos that are going to be tossed out anyway." Remember that? That
was in 2001 - a mere four years ago. It was President Bush's first big public
policy dilemma, which also had nothing to do with cloning. The controversy was
limited to whether the federal government would fund embryonic stem cell
research, which, actually, the government probably could not do legally because
of the Dickey Amendment n15 (which predates embryonic stem cell research) that
prevents the federal government from funding destructive embryo research.

(...)
Take, for example, California's Proposition 71, n20 which was sold to voters as permitting embryonic stem cell research from leftover embryos. However, California's Proposition 71 did much more: It also created a state constitutional right to engage in human somatic cell nuclear transfer. Thus, human cloning is constitutionally
protected by the state constitution of California.

(...)
Repeatedly, we see bills that purportedly outlaw human cloning, but
which actually authorize it. For another example of this approach, we need
only look at a law enacted in New Jersey in 2004 that authorizes human cloning, implantation, and gestation through the ninth month. n27 The wording of
the law is sneaky. First, it authorizes human somatic cell nuclear transfer.
Then, it doesn't outlaw implantation of cloned embryos into a uterus. That which
is not illegal, is by definition, legal. Finally, the statute makes it a
felony to "clone a human being" and establishes punishments for violations,
including "a civil penalty of not more than $ 50,000, or imprisonment for a term of
not more than five years, or both, for each such incident."

MICHAEL J. MALINOWSKI, Legal Limitations on Genetic Research and the Commercialization of its Results, 54 Am. J. Comp. L. 45 (2006)

Given its deep commitment, the impact of biotechnology
on the U.S., both economically and in terms of delivery of health care,
will become significantly greater over the next several years and well into
the foreseeable future.

Joanna K. Sax, The States "Race" with the Federal Government for Stem Cell
Research, 15 Ann. Health L. 1 (2006)

Conclusion: In recognition of the practical federal ban on stem
cell research, private investors and states took initiative to promote
the scientific, medical, and economic potential of stem cell research. This
dissent against federal policy may lead to state competition for researchers
and industry, but more likely, it will induce a federal reaction. It is
unclear at this time whether the federal government will enact policy to support
the ethical promotion of therapeutic research or ban stem cell research,
thus stifling progress in this country for years to come.

Website on famous plagiarists

John P. Lesko has a website on plagiarism at famousplagiarists.com.

Both Laurence Tribe of Harvard Law School and Martin Luther King have entries on the website. Michael Bolton, who lost $5.4 million for copyright infringement on an Isley Brothers song, also appears.

Lesko writes:

Why would a member of academia choose to lift the language of a source text and attempt to foist it off as his own? Why would someone choose to take such a risk with their academic career? Common sense just doesn't seem to offer an answer as to why a college professor would decide to plagiarize--particularly the work of the students he has been mentoring as happens on occasion.

Unless empirical observation teaches that there are not severe consequences to plagiarism, as illustrated by the Harvard Law cases.

**
Lesko discusses the numerous resources for students to copy texts for papers. Interestingly, there are similar resources for ministers to copy sermons.

from the St. Louis Post-Dispatch (October 17, 2005):

Given the harried schedules of most preachers (not to mention
university presidents) it is not surprising that some turn to homiletic aids. The Rev. Timothy Merrill is a senior editor at Homileticsonline.com, a
subscription-based Web site at which preachers pay $59.95 per year for tools to help them craft a better homily.

He likened homiletics to a grocery store, with all the ingredients
for a good homily lining the store's aisles. "We just do the shopping for
preachers who are too busy and we bring those ingredients home and put them all on the kitchen table," said Merrill. "But once the ingredients are on the table, it's
up to you to mix them together, put them in the oven and come up with your final
product."

The report also included the text:

The Rev. Donald Heet is a professor of homiletics (the study of
preparing and delivering sermons) at The Catholic University of America and president
of the Catholic Association of Teachers of Homiletics. He said if the original
homilist is not credited the audience does not know that the preacher they are
hearing is not the original source -- even if the two homilists have some kind of
sharing agreement. "There's no canon law about this, but at best it's
irresponsible and lousy preaching," he said.

Prior art issue to come in challenge to Thomson/WARF patents

Although not explicitly presented in the current re-exam request by PubPat/FTCR, there is likely to be a prior art issue somewhere down the line involving the work of Bongso.

The CAFC recently visited the scope of prior art in Bruckelmyer v. Ground Heaters, 2006 U.S. App. LEXIS 16174.

The CAFC dissent from denial of petition for rehearing begins:

The facts are not in dispute. The '085 and '301 patents were held
invalid because of the existence of two drawings that were stored in the
unpublished archive of an unrelated Canadian patent application by a different
inventor. The drawings were cancelled from the Canadian application before the patent
was granted, and are not referred to in the published Canadian patent. It
is undisputed that these cancelled drawings are not available in any
database or any library, and that no index, no catalog, no abstract suggests
their existence or their content. It is not contested that the only way to
obtain these drawings (although their existence was unknown) is to personally
go to the Canadian Patent Office in Hull, Quebec, and ask to examine the file
wrapper (the prosecution history) of this particular patent, which is entitled
"Portable Construction Heating System".

The CAFC noted: Foreign knowledge is not prior art unless it is patented or
published.

The CAFC cited In re Tenney, 45 C.C.P.A. 894, 254 F.2d 619, 626-27 for the statement:
The law sets up a conclusive presumption to the effect that the public has knowledge of the publication when a single printed copy is proved to have been so published.

The CAFC also noted: In In re Cronyn, 890 F.2d 1158, 1160 (Fed. Cir. 1989), this court explained that "The statutory phrase 'printed publication' has been interpreted to mean that before the critical date the reference must have been sufficiently
accessible to the public interested in the art; dissemination and public
accessibility are the keys to the legal determination whether a prior art reference was 'published.'"

The CAFC cited the more recent case: In re Klopfenstein, 380 F.3d 1345 (Fed. Cir.
2004).

July 21 issue of Science discusses re-exam of WARF stem cell patents

Further to the PubPat re-exam request of the Thomson / WARF patents, the July 21 issue of Science has some discussion of the matter.

Eli Kintisch, "Groups Challenge Key Stem Cell Patents," 313 Science 281 (21 Jul 06)

The WARF patents should not have been granted because the work was obvious and not new.

WARF's patents cover the use, sales, or research on stem cells obtained from primates--regradles of who makes them or how. Experts say the patents are broad because they cover both actual cell lines and general descriptions of making them.
[As noted in IPBiz, there is a research exemption at 35 USC 271(e)(1) which was broadly construed by the US Supreme Court in Merck v. Integra. Science saying that WARF's patents cover "research on stem cells" can be strongly questioned. The failure of Science to mention the research exemption can also be strongly questioned.]

Harvard's Melton calls Warf's licencing terms "onerous, restrictive, and uncooperative" barriers to cures.

FTCR says first two patents are invalid because they cover a technique that was published before 1995. They cite a patent granted in 1992 to Australian Robert Williams. [IPBiz has noted that the Williams' patent comprises data only on mice, unlike the patents of Thomson which comprise data on primates and on humans. Williams never successfully used a technique on primates or humans prior to Thomson's disclosure, a fact that neither FTCR nor Science tell you.]

techniques mentioned in a 1990 paper and scientific books render Thomson's work "obvious to someone skilled in the art"

Experts say the challenges touch on fundamental difficulties about obviousness and novelty claims. [IPBiz suggests that the anticipation/novelty argument of FTCR is not strong and does not present a fundamental difficulty.]

quote Allan Robins.

Bill Warren says the PTO could decide not to review the patents because two of four key references FTCR cites were previously reviewed by the PTO.

**

In an article by Eugenie Samuel Reich in the December 24, 2005 issue of New Scientist
concerning the unfolding scandal of the work of Hwang Woo-Suk, one has a quote from Harvard's Melton:


Observers are now unsure what to believe. "There are so many conflicting
reports," says Doug Melton, a stem-cell biologist at Harvard University.

Stratagene loses jury verdict to Invitrogen over infringement of US 4,981,797

Stratagene, no stranger to patent infringement contests, lost a jury verdict to Invitrogen on a patent concerning E. coli cell products.

The jury determined that Invitrogen's 4,981,797 patent is valid and that Strategene willfully infringed between 1997 and 2001.

In a separate matter, PubPat is seeking to contest through re-examination the validity of claims of WARF's US 5,843,780 and 6,200,806 concerning embryonic stem cells.

Steely Dan accuse Owen Wilson of knock-off in Dupree?

According to SFGate, in a letter posted on their Web site and addressed to Owen Wilson's brother Luke, Steely Dan band members Donald Fagen and Walter Becker label Owen Wilson's supposed rip-off of their 2001 Grammy-winning track as "uncool."

In the movie "You, Me, and Dupree," Owen Wilson plays slacker Dupree, who becomes an unwelcome guest of his pal Matt Dillon and his wife Kate Hudson -- and Fagen and Becker draw parallels with their Randolph Dupree character, a traveling musician who "comes back home to plan (his) next move from the comfort of (his) Aunt Faye's couch."

One comment to the story: This is hilarious...this is almost as good as the fundie anti-choice guy who mistook an article in the Onion (http://tinyurl.com/zm2on)
for an actual editorial.

The San Jose Mercury News noted:

Larry Solters, a spokesman for the band's management company, declined to comment on any details beyond the letter, including whether Wilson showed up to the show or if legal action would be taken.

Hmmm, a copyright action based on the name/plot in a song? Songs have been expanded into movies (e.g., "Ode to Billy Joe" starring Robby Benson).

Plagiarism at SIU?

In an academic spat, SIUE Chancellor Vandegrift was accused of plagiarism in a speech and defended himself by saying the speech was written by his staff, who told him they thought using the remarks was acceptable because they weren't used in an academic paper.

In the context of a Martin Luther King Jr. Day welcoming address, full attribution might not be necessary, BUT arguing that plagiarism in oral remarks is acceptable probably is overreaching.

Nevertheless, a full apology was made. "I will take steps to ensure that all comments are properly acknowledged in the future, regardless of the venue in which they are given," Vandegrift said.

It does seem that plagiarism issues have been more fully addressed at Ohio University and Southern Illinois University than they were at the Harvard Law School. Nobody at OU or SIU tried the "different culture"/"stealing is all right" gambit employed at Harvard.

***

There is some irony in the plagiarism charges surrounding a speech on Martin Luther King Jr. day. There were charges of plagiarism against Dr. King concerning his thesis at Boston University:

On the evidence, there can be little doubt that he plagiarized his Ph.D. dissertation at Boston University from an earlier one by a man, now deceased, named Jack Boozer. Pappas compares eight or more passages from Boozer's thesis with passages from King's in which the ideas and phrasing are virtually identical. He also cites several passages in which King and Boozer make almost identical mistakes in citation or punctuation.

Barry R. Gross concluded:

The academy is not a business; it cannot point to a bottom line of profit to justify its existence. Nor is the academy a political entity; it cannot point to accomplishment in statecraft or public welfare to justify its existence. All it can point to is its guarantee that, insofar as humanly possible, the intellectual efforts produced under its aegis are genuine, that its assertions are believed to be correct, are believed to be made without knowing bias, and are made originally by the authors who claim them. And if the academy cannot say that, it can say nothing at all.

The wikipedia noted:

Although several newspapers had the story for over a year, none published it, later prompting speculation that the story had been withheld due to political correctness.

The incident was first reported in December 3, 1989 edition of the Sunday Telegraph by Frank Johnson, titled "Martin Luther King--Was He a Plagiarist?". The fact that non US media broke the story first is described as an indication of how sensitive the matter is in U.S. The incident was then reported in U.S. in the November 9, 1990 edition of the Wall Street Journal under the title of "To Their Dismay, King Scholars Find a Troubling Pattern". Several other newspapers then followed with stories, including the Boston Globe and the New York Times.

***
Further discussion of the matter appears here:

During the eight years I wrote columns for USA Today, I asked the editor if I could do a column on King’s plagiarism, however, I never got permission. I had read the story of King’s thievery in the London papers during a stopover from one of my trips from the Middle East. The editor of USA Today either did not believe me or more probably did not want to take the heat for breaking the story. The Wall Street Journal broke the story a couple of months later although they did so gingerly.

***
A rather intense story of the King matter appears in a piece by Alan Stang. Therein there is quotation of significant text by one Professor Gerry Harbison, of the Chemistry Department at the University of Nebraska. Also, there is discussion of an article in Chronicles in Jan. 1991 by Boston University president Jon Westling, denying the existence of plagiarism in King's thesis. There is discussion of Peter Waldman of WSJ. Stang suggests a "white" man would have lost his degree, but the story of Glenn Poshard of SIU suggests otherwise.

Nanotechnology and fullerenes

According to a press release, Lux Research and Foley & Lardner LLP reviewed all issued U.S. patents relating to eight classes of nanomaterials: 1) carbon nanotubes, 2) metal nanoparticles, 3) aerogels, 4) ceramic nanoparticles, 5) dendrimers, 6) quantum dots, 7) fullerenes, and 8) nanowires. The analysis reviewed 2,738 patents in total, covering 52,148 relevant claims that cross seven application categories.

It's not clear why carbon nanotubes are separated from fullerenes, because all carbon nanotubes are fullerenes (not all fullerenes are nanotubes, eg buckyballs.)

The press release also notes:

Carbon nanotube and quantum dot applications in electronics, where many crowded and vulnerable patents indicate a high likelihood of legal wrangling, are battles worth fighting. The large addressable markets relevant to these nanomaterials justify the cost of navigating the unfavorable patent outlook.

In healthcare/cosmetics applications nanomaterials with crowded or vulnerable patent landscapes like dendrimers, ceramic nanoparticles, and metal nanoparticles represent battles worth fighting because of the broad applicability of these materials to a number of large addressable markets.

Hidden opportunities - characterized by a favorable patent outlook and large market potential - occur in energy applications of ceramic nanoparticles like high-performance cathodes in the $48 billion battery market, and in electronics applications of nanowires which could keep Moore's Law going in the next decade.

WARF patent dispute driving U.S. scientists overseas?

Lifenews reports: One researcher, Jeanne Loring, who directs human embryonic stem cell research at the Burnham Institute for Medical Research in California, told the Contra Costa Times newspaper that the patent dispute is driving some scientists overseas.

"The patents are impeding our research," Loring said. "They're more important than what's going on in the Senate right now.

"It is making scientists go overseas to do this sort of research," she added. "It isn't the funding that's sending us overseas. It's the patent issues."

IPBiz notes that under the U.S. Supreme Court decision in Merck v. Integra, researchers in the U.S. would have an exemption from patent infringement for purely research activities. Thus, an argument that patent issues are driving stem cell researchers overseas is purely bogus.

The issue is the ties of researchers TO COMMERCIAL ENTITIES. Further, if a product were developed overseas that fell within the scope of claims of a U.S. patent, making the product overseas would not immunize the product from patent infringement if the product were imported into the U.S.

The lifenews article referred to the re-exam request of PubPat and FTCR as a "lawsuit," which it is not: The Public Patent Foundation, a nonprofit group that represents the public in patent policy, joined in the lawsuit.

The re-exam request asserts that U.S. Patent No. 5,166,065 anticipates under 35 U.S.C. 102(b) the claims of U.S. Patent No. 5,843,780 and 6,200,806. The problem is that the '065 patent does NOT disclose the existence of primate or human embryonic stem cells. Further, the re-exam request failed to note that the '780 patent explicitly noted that the use of LIF (disclosed in the '065 patent) failed to create human stem cell lines. The chances of the anticipation argument raising a substantial new question of patentability at the USPTO are slight. Whether the obviousness argument might fly is a different issue, especially with the uncertainty introduced by the Supreme Court review in KSR v. Teleflex. As a headsup in the Supreme Court case, petitioner KSR’s main brief to the Supreme Court is due on or before August 22, 2006. An amicus brief in support of KSR, or in support of neither party, is also due on August 22.

Separately, the general argument in the re-exam request that all the work was done 25 years ago and that Thomson was following a pre-existing recipe is a two-edged sword. If it were true that all the work on human embryonic stem cells were done 25 years ago, then why would PubPat and FTCR be seeking to invalidate the patents in order for researchers to do work in 2006? By their reasoning, the work on mouse embryonic stem cells renders work on human embryonic stem cells "obvious".

Hwang Woo-Suk tried to clone mammoths

According to a Reuters report on July 25, Hwang Woo-Suk tried to clone mammoths: "We secured mammoth tissues from glaciers and tried cloning three times, but failed," Hwang said.

During the third hearing in his trial, Hwang said his team was given a 1 billion won (1.05 million dollars U.S.) grant from South Korea's powerful SK Group in 2005 and the money was supposed to be used for "peripheral activities related to the research". Hwang controlled the money and used part of it to clone tigers, pay for a junior scientist's housing, overseas trips for team members and for a scientist's wedding.

US Stem Cell Scientists Moving to Europe?

Britain's science minister, David Sainsbury, expects American scientists will move to Europe to conduct embryonic stem cell research.

There was no comment on the moves within the Newcastle group.

The EU vote on funding embryonic stem cell research

The EU voted to fund research on embryonic stem cells. Curiously, there was a provision against embryo destruction. The Times of Malta discussed this seeming inconsistency:

Competitiveness Minister Censu Galea argued that Malta had no problem with research making use of stem cells from naturally aborted embryos or cells deriving from blood chords, but it objected to research carried out on clone lines available on the market.

The German delegation accepted the final draft where a statement was included stating that the EU will not finance the destruction of human embryos.

But, at a press conference later, the Commissioner for Science and Research, Janez Potocknik, said that although the EU will not be funding such research itself, the destruction of the embryo was an inevitable phase in the process. It is simply that the EU will not be involved in that phase.

Asked specifically whether this was not a "fudged" solution, given that such research will ultimately involve the destruction of embryos, the commissioner said smilingly: "I don't know what you want me to say".

The position advocated by Malta was previously held by a larger voting block, including Germany and Italy.

The problem with promoting gamma hydroxybutyrate (GHB)

The case of Dr. Gleason concerning the off-label promotion of Jazz Pharmaceutical's Xyrem has attracted some attention.

Doctors are free to prescribe drugs for uses which have not been approved by the FDA (off label uses). Drug companies are NOT free to advertise off label uses. Thus, there is some incentive for drug companies to "encourage" doctors to do what the drug companies can't do. A variant of this problem came up in the Hatch-Waxman context with the drug Neurontin, discussed by me in Intellectual Property Today.

Dr. Gleason got over $100,000 last year from Jazz. That alone probably is not the problem in the aggressive stance taken against Dr. Gleason. The active ingredient in Xyrem is gamma hydroxybutyrate, or GHB, the "date rape" drug. That reality sets this case a bit apart.

Boston Communications settles patent case; stock goes up

Reuters: Boston Communications Group Inc.'s share price more than doubled July 21, 2006 after the company said it will pay $55.3 million to Freedom Wireless Inc. to settle a patent litigation.

The BCI case had been one in which the patentee, Freedom Wireless, had been depicted as a patent troll. Some will view this as a smaller version of the NTP v. RIM case.

Schwarzenegger tells Genest to loan CIRM up to $150 million

The National Review blog notes: On Thursday morning [July 20, 2006], the governor sent a letter to state Finance Director Mike Genest asking him to loan up to $150 million to the stem cell agency [CIRM] from the state's general fund. The money is to be repaid with interest when lawsuits challenging the constitutionality of the California program are resolved. If the stem cell agency is declared constitutional, it can issue bonds to finance its work.

The article points out the complexity in California's proposed stem cell research created by the presence of the WARF/Thomson patents on stem cells (including US 5,843,780 and 6,200,806). The article included an excerpt from an article in the Wall Street Journal:

The state of California was pulled into the patent battle after voters there approved a ballot measure in 2004 that will fund as much as $300 million of research each year for 10 years, at a total cost to state taxpayers of as much as $6 billion. Mr. Simpson's taxpayer group is one of several that pressured the new state agency, the California Institute for Regenerative Medicine, to seek a return to taxpayers on its investment.

The agency is proposing to take 25% of the revenue that universities generate from patenting discoveries made with the stem-cell funds. In March, Ms. Donley said that WARF would consider any such move a "commercial" use of its patents and demand a cut of the state's take. Edward Penhoet, vice chairman of the California stem-cell agency's oversight board, calls WARF's argument "unprecedented," and the parties haven't reached any agreement.

Mr. Simpson says it was those discussions that led him to decide the patent is "damaging the taxpayers of California" and to start organizing the re-examination request being undertaken today.

The National Review blog does not point to the irony in the California group challenging Wisconsin's WARF for enforcing patents, when California's CIRM is positioning itself to do the same thing (i.e., gain royalties by enforcing patents).

The National Review does state:

What's been lost in the discussion on stem cell research is the economic component of the debate. These are for profit entities that are lining up for state and Federal money. We need to remember that. I wonder if Democrats would feel differently if the money dedicated for embryonic stem cell research was framed as inevitably a tax break for big pharma?

As a general matter, it's a bit more complex. "Not for profit" entities are lining up for state and Federal money, and then aligning themselves with "for profit" entities through the Bayh-Dole Act (and whatever variant thereof California and other states may develop). The incentive for the alignment comes through the presence of patents.

***

The Jackson News-Tribune states:

"It's absolutely absurd that one person or organization could own the rights to life itself," said John Simpson, stem cell project director of the Foundation for Taxpayer and Consumer Rights [FTCR], based in California.

***

Neither the National Review nor many of the newspapers covering the story have noted that the irony that Wisconsin's WARF has licensed the patents to Geron, a Menlo Park, California company.


***

Of the FTCR/PubPat challenge to Thomson's 5,843,780 and 6,200,806 as being anticipated by earlier work (US 5,166,065 of Williams), one notes Williams in the '065 patent did NOT report the creation of hESC but rather stated that LIF could be used to keep (hypothetical) hESC from differentiating. If it were so obvious that LIF could do the trick, one is puzzled by the fact that neither Williams nor anyone else was able (prior to the time of Thomson's discovery) to use LIF to create a stable hESC line. As to the anticipation argument made by PubPat, it is likely that PubPat will be the one caught with its hand in the cookie jar, because this dog won't hunt.

Bob Park on story in Nature about Taleyarkhan's bubble fusion

On July 14, IPBiz noted that the Purdue University review of the work of Rusi Taleyarkhan was completed, but would not be made public.

On July 21, Bob Park noted:

Four years ago Rusi Taleyarkhan, then at Oak Ridge, claimed in Science magazine that he had achieved d-d fusion in collapsing bubbles. The bubble burst three months later, but he moved to Purdue and again claimed fusion. Others still found nothing. In March of 2006, Purdue, citing "extremely serious concerns," announced a full review of Taleyarkhan's work. A story in Nature this week raises serious questions about slow progress and secrecy of the review.

To date, Bob Park has not commented on the failure of Science to make public the results of the Brauman panel, investigating how Science published fraudulent work of Hwang Woo-Suk.

**
On June 21, the New York Times (section A, page 15) had noted:

Purdue University has completed a review of ''tabletop fusion''
experiments by one of its professors but is not saying what it found. In March, the
university announced the review after concerns had been raised over the
research of the professor, Rusi P. Taleyarkhan, who claimed to have induced
fusion by blasting a container of liquid solvent with ultrasonic vibrations. The
university said in March that it would announce its findings, but in a
statement yesterday, Charles O. Rutledge, vice president for research, said the
review's findings and any subsequent actions by the university would remain
confidential.

The New York Times has not commented on the absence of a report on the findings of the Brauman panel.

The arguments concerning the re-exam of WARF's patents

Sciencenow says of the FTCR/PubPat challenge to the WARF/Thomson patents on stem cells:

Experts say the case raises fundamental questions about the nature of patents. "You can say the technology was almost identical to what they did in mouse [cells], so you could argue it was obvious," says Allan Robins, molecular biologist with Irvine, California–based stem cell startup Novocell. But, "there had been failures in rats and pigs--therefore you could argue that it wasn't obvious." PTO can take up to two years to decide whether to do a full re-examination, and another year or more to rule.

Sciencenow quotes Dan Ravicher of PubPat:

"They tried to pull a fast one on the Patent Office--they've been caught with their hand in the cookie jar."

IPBiz says: The idea that US 5,166,065 anticipates the claims of US 5,843,780 and US 6,200,806 (Thomson) is not well-founded and will not fly at the USPTO. The fact that US '780 explicitly says that LIF didn't work for hESC may play a role, and, if it does, that will be an important patent prosecution practice concept to remember. Many patent practitioners are averse to recording things that don't work in an application for fear of introducing undue limitations to claim scope.

US '065 did NOT describe the making of hESC. It did suggest that, once one had hESC, that LIF could be used to keep them from differentiating. Since that time, it has been learned that LIF works differently between mouse stem cells (the subject of the '065 patent) and human stem cells, a fact not discussed in the challenge by PubPat to the WARF patents.

WISCTV strikes a more conciliatory note about the issue:

"I think it's really born in the fact that they'd like to use the patents to build their program for free. We're certainly willing to work with them to find an equitable solution, somewhere between collaboration and a license I'm sure there's a solution, and we continue to talk with them about that," said Elizabeth Doyle, director of Business Development for the Wisconsin Alumni Research Foundation.

Wistechnology notes:

In challenging the WARF patent, the Public Patent Foundation submitted what it said was unseen "art" or evidence that the previous work of other scientists made the derivation of human embryonic stem cells "obvious and therefore unpatentable."

Dr. Jeanne Loring, a stem cell scientist with the Burnham Institute for Medical Research, said the real invention was made 25 years ago, when embryonic stem cells first were discovered. Loring said Thomson "just followed a recipe written by other scientists, and there's nothing patentable about that."

Dispute over inventorship in Erbitux patent

from AP: In a 2003 patent suit, Yeda Research and Development Co. of Israel sued ImClone, which has an exclusive license for the formula used in Erbitux to inhibit tumor cells, and Aventis, claiming three of its researchers should be named as the inventors. The current patent names Dr. Joseph Schlessinger, Chairman of Pharmacology at the Yale School of Medicine, as the inventor along with six others, three of whom even the defense has agreed do not belong on the patent.

In recent weeks, U.S. District Judge Naomi Buchwald has heard testimony from Sela, Schlessinger and other top cancer researchers. She has not yet ruled, and it is not clear when she might do so. But she was critical of many of the arguments presented by lawyers for ImClone and Aventis during closing statements Wednesday.

**
Thus, Erbitux is brought to us through the Bayh-Dole Act.

**
Of academics and patents:


Sela said he had never paid much attention to patents.

"I don't mind if I don't take a patent, unless it's stolen from me. Then I have to react," he said. "At the beginning, when I first saw it, I was in a state of shock. I mean, money is not important, but my name and my science, my honor demanded" that he be put on the patent.

Dr. Esther Aboud-Pirak, another of the three Yeda researchers, said she was 27 years old and disinterested in patents when she did the bulk of the research work on the method.

Under cross examination, Aboud-Pirak grew testy as she acknowledged that each of the three researchers could share in any money Yeda receives as a result of the litigation.

(...)

George Badenoch [Kenyon & Kenyon], a lawyer for ImClone, told the judge that Yeda did nothing to pursue the claim from 1988, when the researchers wrote a paper on the subject, to several years ago, after they learned a patent was issued in 2001.

"It's not proper now that we have got a blockbuster product for them to come in and say, `Hey, now we want to participate, now we got to be paid.'"

**
Schlessinger has been involved with other drugs:

"This is all a continuum of discoveries that started in the early 1980s," says Joseph Schlessinger, chairman of the pharmacology department at Yale School of Medicine and a co-founder of Sugen, the company that created Sutent. "We are now in a golden age of drug discovery."

The WARF/Thomson patents on stem cells and the Wright Brothers

The invention of three-dimensional control by the Wright Brothers, most pointedly including lateral control, was so basic to any aircraft design that, without it, no aircraft could have flown successfully. The Wrights had a broad patent.

To get around the Wrights' patent, Glenn Curtiss resurrected Langley's Aerodrome, a piece of "prior art" to the Wrights' patent. That particular effort, which incorporated post-Wright insights into a nominal pre-Wright aircraft, failed. Curtiss was making other efforts to get around the Wright patent when World War I intervened, and a patent pool was created. By the time of the patent pool, Wilbur Wright was dead, and Orville had sold his interests, so the dispute no longer involved the Wrights. Although the pool did not create any American-made fighter aircraft used in World War I, it did create a surplus of airplanes after World War I, and the Wright patent was not further litigated prior to its expiry in 1923.

In the re-exam filed against patents of Thomson/WARF, US 5,166,065 is cited as an anticipating reference. There is no disclosure within the '065 of an actual human (or primate) stem cell line, just as there was no disclosure of an aircraft which actually flies in the Langley work. In US 5,843,780, Thomson mentions an unsuccessful attempt at human stem cell formation using LIF.

Without making any judgment on the merits of the re-exam, IPBiz reminds folks that the purpose of the patent system is to reward those who bring novel, useful, and enabled inventions to the public. "Killing off" patents that do work based upon prior art that did not work is probably not a good idea, as the courts indeed determined in the case of the assertions of Curtiss made against the Wright Brothers.

***

Of the history of stem cells, see

Lensch and Daley, Origins of mammalian hematopoiesis: in vivo paradigms and in vitro models.Curr Top Dev Biol. 2004;60:127-96.

A. G. Smith, Annu Rev Cell Dev Biol 17, 435 (2001).

One website describes US 5,166,065 as follows:

USP 5,166,065 (Amrad Corp.) for the use of leukemia inhibitory factor (LIF) in
maintaining ESCs in culture. Human ESCs are included. The European equivalent, EP
380,646, was the subject of controversy.

[IPBiz post 1800]

Paul Jacobs discusses Bush veto of stem cell bill

In discussing the Bush veto of the stem cell bill, Paul Jacobs stated of data sharing:

Another effect [of the veto] is more indirect. Science advances when researchers worldwide are able to pool their data and findings, but researchers in California using state funds who might have collaborated with scientists elsewhere doing federally funded research will not have that luxury.

First, under the Bayh-Dole Act, federally-funded scientists will create patent applications BEFORE they share their data publicly. Thus, they will be "roping off" their inventions BEFORE other researchers see the data. Second, although the intellectual property policy of CIRM is an incoherent and amorphous body, one expects that CIRM-funded scientists will also file patent applications BEFORE disclosing their data. Third, one notes the oddity of Jacobs' speaking of "researchers worldwide" but then limiting himself to "[U.S.]-federally funded researchers."

Jacobs also noted:

Dr. Irving Weissman, a stem-cell researcher and director of Stanford's Institute for Stem Cell Biology and Regenerative Medicine, agrees that the federal restrictions have impeded stem-cell work. He noted, for example, that analyzing the genes from new stem-cell lines cannot be done at federally funded facilities on the university campus.

Jacobs did not mention the problem of the NIH acquiring from MizMedi hospital, and then distributing, a post-2001 hESC stem cell line, and no one did a genetic analysis thereof. The problem was not "where" genes were analyzed, but whether they were analyzed at all.

Jacobs further stated:

Robert Klein, chairman of the committee that is overseeing spending of the state funding, describes Bush's decision as "tragic."

"We could get greater leverage out of our $3 billion if we were able to use federally funded facilities currently in place," said Klein, who led the effort to pass a stem-cell funding initiative in 2004.

Said Stanford Nobel laureate Paul Berg, a critic of the administration: "What many people don't understand is it is not just the money." Equipment and laboratory space supported with federal dollars cannot be used for research with the newer stem-cell lines, he said. That's why money directed toward research from California and other states "is not the whole answer."

Jacobs did not mention that Klein, in the last California primary election, lobbied against a certain candidate (Ortiz) and is lobbying for stem cell funding in other states.

Jacobs does not mention Hwang Woo-Suk in his article, and does not mention "where" the current state of the art in embryonic stem cell research is located.

[IPBiz post 1799]

Lessons to be learned from the use of false data?

In the famous Quillen and Webster [QW] paper of 2001 on patent grant rate, the authors assumed that a patent could NOT issue on BOTH a parent AND a continuing application in order to get their elevated bound (97%) for patent grant rate. That high number later worked its way into the eBay brief before the US Supreme Court.

The patent practitioner of ordinary skill would know that it is true that a patent can issue on BOTH a parent AND continuing applications, and thus that a contrary assumption is against known facts and leads to false numbers.

In "A Patent System for the 21st Century," editors Stephen A. Merrill, Richard C. Levin, and Mark B. Myers handled Quillen and Webster's "assumption" in the following way:

Quillen and Webster noted the possibility that more than one patent could issue from a single disclosure, but because they did not have the data to correct for such occurrences, they based their calculations on the assumption that “parent” patent applications are abandoned when a continuation application is filed.

That is, because QW did not have the correct data, they used wrong data. The wrong data led to a wrong grant rate, which was used in the eBay brief to the Supreme Court. The wrong grant rate was also used in a note in the Harvard Law Review. [The grant rate used by eBay and Harvard is wrong because once accounting is made of multiple patent families, there is no "estimate" for grant rate of 97%, and, if the correct data had been used to begin with, there never would have been a 97% number. Both the first and third papers by QW present "grant rates" in excess of 100%, clearly the result of an unreasonable approach. Parenthetically, one notes that the QW approaches will lead to an incorrect grant rate whenever more than one patent issues from a patent family, whether or not there is a patent on the parent.]

In a discussion by Lisa Jardine of the scandal surrounding Hwang Woo-Suk, one finds

[The Hwang scandal] has brought into the public domain the process of "peer review" - the method of assessment used within the academy to regulate and control research activity. In scientific research, that process is supposed to ensure that the methodology is sound, and that interpretation of data does not lead to misleading or unreasonable claims.

(...)

At the outer envelope of current laboratory research, perhaps the great leap forward might be in the direction indicated by the ambitious investigator, whose impatience to arrive first at the next great scientific milestone overcomes his or her proper experimental caution.

(...)

Had the truth come out at the time, Pasteur would probably have been disgraced. As it was, the vaccine's success was such that no doubts were ever raised. Pasteur was a scientific gambler, whose bet paid off. Gamblers try to force the pace of research, wagering that the experimental results they are currently fudging will come good.

By the time the breakthrough has been properly made - a rabies vaccine, a cure for Parkinson's disease - they hope to have successfully produced the genuine evidence, achieved properly verifiable outcomes.

On the other hand, the scientific community pursues a policy of systematic self-regulating - making sure that the procedures followed are sound, and the data have not been exaggerated or manipulated. False claims, strenuously checked and tested, will eventually fail and be rejected.

Sooner or later, Hwang's bogus stem-cell results would have come to light, when they could not be replicated. But financial incentives in the form of massive amounts of government funding are another matter. Political pressure from governments, pouring money directly into work in research areas they have set their hearts on leading, surely does have the capacity to distort even the best-established procedures.

The Hwang scandal, and the correlative uncertainty of "where" the state of the art in current embryonic stem cell research is located, have not been much discussed in events leading to the Bush veto on July 19, 2006.

The Mercury-News stated:

Bipartisan majorities in Congress oppose his [Bush's] stand. So do a majority of the American people, polls show. They agree with scientists who argue that the spare embryos in question come from fertility clinics, where they'd otherwise be destroyed. Scientists say research on stem cells could lead to cures for Parkinson's disease, Alzheimer's, spinal cord injuries and other illnesses that afflict millions of Americans.

The president's choice for such a signature event is thus fraught with potential political consequences. While it may curry favor with religious conservatives, who compose the cornerstone of his political base, his stand may alienate moderate Republicans, independent voters and others who see the research as key to helping save lives. Most Democrats champion the stem-cell bill, as do many Republicans, including Nancy Reagan, California Gov. Arnold Schwarzenegger and Sen. Orrin Hatch, R-Utah.

Congressional Democrats made clear Wednesday [July 19] that they intend to make Bush's veto a central campaign issue in November's elections, as they vowed at a Capitol Hill rally to fight on to pass the legislation. They lack the two-thirds majorities needed to override Bush's veto in Congress, however; the House of Representatives fell 50 votes short of the total needed when it voted 235-193 Wednesday night to override, cementing Bush's veto at least for this year.

**
The lesson from Hwang Woo-Suk has yet to be learned.


[IPBiz post 1798]

Future problems in the determination of "prior" art?

In the article "Public Access Failure at PubMed," [313 Science 43 (7 July 2006)]:

"The policy also allows posting of papers that differ significantly from the final published version, which has the potential to create intellectual property issues as each public disclosure of the research represents prior art in the eyes of the law."

IPBiz is separately concerned about "early drafts" which appear on the internet and then later submerge, as is the case with some law review articles. Further, in the case of the NAS report on patent reform, the early draft contained some arguments which did not appear in the final draft.

Limitations on continuing applications at USPTO a done deal?

I/P Updates stated:

According to Hal Wegner, Deputy Commissioner for Patent Examination Policy Jay P. Lucas announced in his luncheon speech at the George Mason University Law School on July 18, 2006 that the final rules package on continuation and claim number limitations would be published at some point between Thanksgiving and Christmas this year.

Apart from the negative feedback on the proposed limitations in the public comments, one notes the paper "Patent Continuation Applications" by Schreiner and Doody which appears at 88 JPTOS 556.

***

Lucas did not address the scope of any revisions to the proposal that may be made.

More on the re-exam request of WARF's stem cell patents

Further to the re-exam request on WARF patents of July 18, 2006, one notes that there is an assertion that claims of both US 5,843,780 and US 6,200,806 are anticipated by US 5,166,065.

The abstract of the '065 patent states:

The present invention relates generally to the use of leukaemia inhibitory factor (LIF) in the maintenance and derivation of embryonic stem (ES) cells in culture. The ES cells are maintained and/or derived from animal embryos by culturing said cells or embryos in a culture medium containing an effective amount of LIF for a time and under conditions sufficient to maintain and/or derive said ES cells. The ES cells may be passaged in LIF and used to make chimaeric animals.

Text within the '065 states:

However, it is known that ES cells and certain EC (embryonal carcinoma) cell lines will only retain the stem cell phenotype in vitro when cultured on a feeder layer of fibroblasts (such as murine STO cells, e.g. Martin, G. R. and Evans, M. J. (1975) Proc. Natl. Acad. Sci. USA 72:1441-1445) or when cultured in medium conditioned by certain cells (e.g. Koopman, P. and Cotton, R. G. H. (1984) Exp. Cell Res. 154:233-242; Smith, A. G. and Hooper, M. L. (1987) Devel.Biol. 121:1-91). In the absence of feeder cells or conditioned medium, the ES cells spontaneously differentiate into a wide variety of cell types, resembling those found during embryogenesis and in the adult animal. The factors responsible for maintaining the pluripotency of ES cells have, however, remained poorly characterised.

Also:

Accordingly, a first aspect of the present invention relates to a method for the isolation of embryonic stem (ES) cells from animal embryos in vitro which method comprises deriving ES cells from said embryos in culture medium, said culture medium containing an effective amount of leukaemia inhibitory factor (LIF), for a time and under conditions sufficient for the development of said ES cells. The embryos used may be isolated from animals including, but not limited to, humans and a number of other animal species such as birds (e.g. chickens), mice, sheep, pigs, cattle, goats and fish.

A second aspect of the present invention, contemplates a process for maintaining animal embryonic stem (ES) cells in vitro while retaining their pluripotential phenotype, which process comprises culturing said cells in a culture medium containing an effective amount of leukaemia inhibitory factor (LIF) under conditions sufficient to maintain said cells. The ES cells in accordance with this aspect of the invention include cells from humans, mice, birds (e.g. chickens), sheep, pigs, cattle, goats and fish.

An example is given of a stem cell line from a mouse.

The first claim of the '065 states:

A method for the isolation of embryonic stem (ES) cells from mammalian embryos in vitro which method comprises deriving and maintaining said embryos in culture medium containing an effective amount of recombinant leukaemia inhibitory factor (LIF) for a time and under conditions sufficient for the development of said ES cells.

A paper in the journal Stem Cells (Vol 22, p. 770) in the year 2004 had reported:

Anecdotal and contradictory accounts exist for the action of LIF in the culture of human embryonic stem cells, and the nature of LIF signaling and whether the LIF-STAT3 pathway is conserved in human embryonic stem cells (hESCs) has not been systematically explored.

Separately, mouse stem cells can be cultured indefinitely in the presence of leukemia inhibitory factor (LIF), a glycoprotein cytokine.

Human embryonic stem cells are in many respects similar to mouse embryonic stem cells, but they do not require LIF for their maintenance.

**
The re-exam request makes much of the fact that the '780 and '806 patents of Thomson (WARF) did NOT cite the '065 patent (Williams). HOWEVER, one notes that the '780 patent of Thomson DOES CITE the work of Williams:

Mouse ES cells maintain an undifferentiated state through serial passages when cultured in the presence of fibroblast feeder layers in the presence of Leukemia Inhibitory Factor (LIF) (Williams, et al., Nature 336: 684-687, 1988). If LIF is removed, mouse ES cells differentiate.

The '780 patent does mention LIF:

FIG. 2 is a set of phase-contrast photomicrographs demonstrating the morphology of undifferentiated rhesus ES (R278.5) cells and of cells differentiated from R278.5 in vitro (bar=100 .mu.). Photograph A demonstrates the distinct cell borders, high nucleus to cytoplasm ratio, and prominent nucleoli of undifferentiated rhesus ES cells. Photographs B-D shows differentiated cells eight days after plating R278.5 cells on gel treated tissue culture plastic (with 10.sup.3 units/ml added human LIF) . Cells of these three distinct morphologies are consistently present when R278.5 cells are allowed to differentiate at low density without fibroblasts either in the presence or absence of soluble human LIF.

More importantly, the '780 patent mentions (and the re-exam request does not mention) a previous failed attempt to isolate hESC using LIF:



No other primate (human or non-human) ES cell line is known to exist. The only published permanent, euploid, embryo-derived cell lines that have been convincingly demonstrated to differentiate into derivatives of all three germ layers have been derived from rodents (the mouse, rat, and hamster), and possibly from rabbit. The published reports of embryo-derived cell lines from domestic species have failed to convincingly demonstrate differentiation of derivatives of all three embryonic germ layers or have not been permanent cell lines. Research groups in Britain and Singapore are informally reported, later than the work described here, to have attempted to derive human ES cell lines from surplus in vitro fertilization-produced human embryos, although they have not yet reported success in demonstrating pluripotency of their cells and have failed to isolate permanent cell lines. In the only published report on attempts to isolate human ES cells, conditions were used (LIF in the absence of fibroblast feeder layers) that the results below will indicate will not result in primate ES cells which can remain in an undifferentiated state. It is not surprising, then that the cells grown out of human ICMs failed to continue to proliferate after 1 or 2 subcultures, Bongso et al. Hum. Reprod. 9: 2100-2117 (1994).