•     By Kevin E. Noonan

    Wall_street_journal_2
    In retrospect, it was eerily prescient.  The Wall Street Journal published an article Saturday, hours before the tragedy at Churchill Downs where Eight Belles, a two-year old filly was euthanized because she broke both front ankles after finishing second in the Kentucky Derby.  That article was about the danger to thoroughbred horses stemming from severe inbreeding over the past 50 years.

    The problems stem from the racing success of the stallion Native Dancer, who was an ancestor of every one of the twenty horses running in this year’s Derby.  And although this is the first time every horse in the race was related to this great progenitor horse, each of the last thirteen Derbys were won by one of his descendants.  In all, the article estimates that 75% of all U.S. thoroughbreds are related to Native Dancer.

    The reason for the success of Native Dancer’s line comes from the propensity for these horses to be "precocious" and "speedy," particularly at the age when they are running prestigious races like the Kentucky Derby.  But these positive attributes come with a "tragic flaw":  these horses have difficulties with their feet, most recently and tragically (before last Saturday) illustrated by last year’s Kentucky Derby winner, Barbaro.  Barbaro won the Derby, but was injured during the running of the Preakness Stakes and ultimately euthanized after a valiant and public struggle to heal well enough to be put out to stud.  Barbaro was Native Dancer’s great-great-great grandson.  Short racing careers (although rarely as tragic as Barbaro’s) have been a characteristic of the Native Dancer line.

    One reason for the excessive inbreeding to the Native Dancer line is that the overall number of stallions producing foals has dropped from 6,263 in 1992 to 3,083 in 2007, and the number of dams mated to each stallion last year was (on average) 60, up from 42 in 1998, according to the Journal.  The reason is economic:  using "established" or "proven" stallions increases the likelihood that the mating will produce a winner, and winners are what today’s horse set wants.  Part of this is due to the transition of the horse-owning population from essentially rural owners with generations of tradition, to today’s amalgam of "billionaire sheiks," entertainment figures and others with less interest in tradition than in profits.  This trend has been exacerbated by the increase in the prices paid for one-year olds, which last year was an average of $101,347.

    The dangers of inbreeding have been known for many years with domestic animals, such as dogs and cats.  For example, Irish setters are prone to early blindness and Bernese Mountain dogs, a particularly popular breed, have a shortened life expectancy.  The problem threatens to become more pronounced as the products of genetic engineering are applied to animal breeding of farm animals.  The technology used to produce the cloned sheep Dolly is being used to clone a prize bull, a holy grail of animal breeders since Clement Markert produced a triple allophenic mouse at Yale thirty years ago.  (Markert’s student, Jon Gordon, produced the first transgenic mouse a few years later in Frank Ruddle’s lab.)

    Yet such animals threaten to have an even greater, and much more rapid, effect on genetic diversity than Native Dancer.  Although Native Dancer is an ancestor of a great many of today’s thoroughbreds, each generation involved crosses of animals merely related to Native Dancer and thus carrying at least a portion of their genetic complement from other lines.  A Native Dancer clone, on the other hand, would effect transfer of the same genes in every mating, and the risks of producing unexpected and deleterious mutations or variants, or combinations thereof, are incalculable.  It is significant in this regard to recall that the cheetah population, one of the most endangered of the large cats, is particularly at risk because their population went through a "bottleneck" about 10,000 years ago, making all living cheetahs distant cousins (see "Tears of the Cheetah" by Steve O’Brien).

    Ironically, Eight Belles was only distantly-related to Native Dancer:  her father, Mr. Prospector, was the sire of her dam’s dam with no other Native Dancer relatives in her immediate pedigree.  It is impossible to know whether Eight Belles’ fate was related to her genetic heritage.  But it is also impossible to establish that it was not, raising the specter of some type of genetic deficiency (e.g., susceptibility to diseases) that may threaten food production in ways that could dwarf the fears attendant to the current transgenic animal and crops debate.

  •     By Donald Zuhn

    Sipo_2
    On April 25th, the State Intellectual Property Office (SIPO) of China announced the launch of an online patent database that allows for English language searches of the bibliographic data and abstracts of published Chinese patent documents.  In particular, the database permits one to search the following fields of invention and/or utility model patent publications:  publication number, publication date, application number, application date, title, abstract, IPC, applicant, inventor, patent agent, patent agency code, priority, and province/country code, or alternatively, to do combination searches on multiple fields.  The new database can be accessed here.  In its announcement, SIPO indicated that the new database was being launched with the intent of collecting user feedback, which the Office noted would be crucial for further improvement of the database.

  •     By Sherri Oslick

    Gavel_21
    About
    Court Report:  Each week we will report briefly on recently filed
    biotech and pharma cases, and a few interesting cases will be selected
    for periodic monitoring.


     Pfizer Inc. et al. v. Teva Pharmaceuticals USA Inc.

    1:08-cv-00237; filed April 25, 2008 in the District Court of Delaware

    Infringement of U.S. Patent No. 5,273,995 ("[R-(R*R*)]-2-(4-fluorophenyl)-beta, delta-dihydroxy-5-(1-methylethyl-3-phenyl-4-[(phenylamino) carbonyl]- 1H-pyrrole-1-heptanoic acid, its lactone form and salts thereof," issued December 28, 1993) based on Teva’s filing of an ANDA to manufacture a generic version of Pfizer’s Lipitor® (atorvastatin calcium, used to treat high cholesterol and heart disease).  View the complaint here.  As reported here, plaintiffs have previously asserted this patent against Teva; the present complaint includes an additional generic Lipitor® dosage form.


    AstraZeneca AB et al. v. Teva Parenteral Medicines Inc. et al.

    1:08-cv-00238; filed April 25, 2008 in the District Court of Delaware

    AstraZeneca AB et al. v. Teva Parenteral Medicines Inc. et al.
    3:08-cv-02014; filed April 24, 2008 in the District Court of New Jersey

    The complaints in these cases are substantially identical.  Declaratory judgment that Teva’s Paragraph IV notice fails to meet the relevant statutory provisions.  Also, infringement of U.S. Patent No. 5,877,192 ("Method for the Treatment of Gastric Acid-Related Diseases and Production of Medication Using (-)Enantiomer of Omeprazole," issued March 2, 1999) following a paragraph IV certification as part of Teva’s filing of an NDA (under § 505(b)(2) of the Food, Drug and Cosmetic Act) to manufacture a generic version of AstraZeneca’s Nexium I.V.® (esomeprazole for injection, used for the short-term treatment in the healing and symptomatic resolution of diagnostically-confirmed erosive esophagitis).  View the Delaware complaint here.


    Sanofi-Aventis U.S. LLC et al. v. W.C. Heraeus GmbG

    3:08-cv-02048; filed April 25, 2008 in the District Court of New Jersey

    Infringement of U.S. Patent No. 5,338,874 ("Cis oxalato (trans 1-1,2-cyclohexanediamine) PT(II) Having Optically High Purity," issued August 16, 1994) based on Heraeus’ filing of a DMF (drug master file) with the FDA for the manufacture of Eloxatin® (oxaliplatin for injection, used to treat colorectal cancer).  View the complaint here.

  • Calendar_20
    May 15, 2008 – The Federal Circuit: A National Court of Appeals: Addressing New Challenges (U.S. Court of Appeals for the Federal Circuit) – Washington, DC

    May 28, 2008 – Advanced Patent Licensing 2008: What You Need to Know Before Licensing Your Patent (Practising Law Institute) – New York, NY

    May 28-30, 2008 – PharmaBiotech IP Summit (Worldwide Business Research) – Philadelphia, PA

    June 11, 2008 – Advanced Patent Licensing 2008: What You Need to Know Before Licensing Your Patent (Practising Law Institute) – San Francisco, CA

    June 16, 2008 – Prior Art & Obviousness 2008: The PTO and CAFC Perspective on Patent Law Sections 102 & 103 (Practising Law Institute) – San Francisco, CA

    June 17-20, 2008 – BIO International Convention (Biotechnology Industry Organization) – San Diego, CA

    June 18-20, 2008 – Fundamentals of Patent Prosecution 2008: A Boot Camp for Claim Drafting & Amendment Writing (Practising Law Institute) – New York, NY

    June 23, 2008 – Multilateral Patents (Law Seminars International) – San Francisco, CA

    July 1, 2008 – Prior Art & Obviousness 2008: The PTO and CAFC Perspective on Patent Law Sections 102 & 103 (Practising Law Institute) – New York, NY

    July 9-11, 2008 – Fundamentals of Patent Prosecution 2008: A Boot Camp for Claim Drafting & Amendment Writing (Practising Law Institute) – San Francisco, CA

    July 16, 2008 – Patent Claim Construction Workshop (Law Seminars International) – Seattle, WA

    July 24-25, 2008 – Advanced Patent Prosecution Workshop 2008: Claim Drafting & Amendment Writing (Practising Law Institute) – New York, NY

    August 11-12, 2008 – Advanced Patent Prosecution Workshop 2008: Claim Drafting & Amendment Writing (Practising Law Institute) – San Francisco, CA

    ***Patent Docs is a media sponsor of this conference or CLE

  •     By Donald Zuhn

    Abbott_laboratories
    In March, we reported on the lobbying expenditures for a number of biotech and pharmaceutical companies in 2007.  For example, we noted that Millennium Pharmaceuticals had spent $1.28 million, Genentech $1.8 million, and AstraZeneca $4.1 million in 2007.  Topping each of these companies, however, was Abbott Laboratories, based in Chicago’s northern suburbs, which spent $4.4 million on lobbying in 2007.  Most of these funds presumably went to lobby on the patent reform and follow-on biologics bills that were being considered by Congress last year.

    On Wednesday, Forbes.com reported that Abbott spent $880,000 on lobbying in the first quarter of 2008.  Abbott’s first quarter expenditures are probably not too surprising considering that patent reform legislation only recently stalled in the Senate.  With follow-on biologics legislation on the backburner and the economy struggling, it will be interesting to see if biotech and pharmaceutical companies begin to cut back on lobbying in the second quarter.

    For additional information regarding this topic, please see:

    • "Abbott Spent $4.4 Million on 2007 Lobbying Effort," March 17, 2008
    • "Biotech and Pharma Companies Spent Millions on Lobbying in 2007," March 5, 2008
    • "Millennium Pharmaceuticals Spent $1.28 Million on Lobbying in 2007," February 8, 2008

  • Seattle #1 Law Seminars International (LSI) will be holding a Patent Claim Construction workshop on July 16, 2008 in Seattle, Washington.  The workshop will provide information on:

    • Current case law and recent federal circuit developments.
    • The development of claim construction theory and practice.
    • Litigation strategies from plaintiff and defendant perspectives.
    • Managing the prosecution process for the most effective claim drafting on a portfolio-wide basis.
    • Drafting an application that complies with today's standards for a litigation or license ready patent.
    • Effective use of graphics.

    Brochure
    In particular, LSI's faculty will offer presentations on the following topics:

    I.  The development of claim construction theory and practice

    • Origins of patent claiming requirements;
    • Patent claims' role to establish boundaries of exclusive rights & provide public notice of those rights;
    • "Intrinsic" & "extrinsic" evidence of the meaning of patent claims;
    • Legal theories of claim interpretation.

    II.  Current case law and recent federal circuit developments in claim construction

    • Review of 2007-2008 case law of the Federal Circuit on selected claim construction topics, such as whether preambles limit claim scope;
    • Substantive and procedural issues.

    III.  Ways for prosecutors to create patents worthy of litigation and tips to make it easier for litigators to defend

    • In-house counsel perspective: Managing the prosecution process for the most effective claim drafting on a portfolio-wide basis;
    • Outside counsel perspective: Drafting an application to comply with today's standards for a litigation or license ready patent;
    • Responding to office actions that avoid file wrapper estoppel and increase the chance that allowed claims will be infringed.

    IV.  Litigation strategies from plaintiff and defendant perspectives

    • Advantages and disadvantages of evidentiary hearings;
    • Laying the groundwork for successful summary judgment motions;
    • What to do after the claim construction ruling.
    • Getting claim constructions that strengthen all of your best defenses.

    V.  Using graphics to help win claim construction disputes

    • The increasingly important role of graphics in claim construction disputes;
    • Elements of a successful graphic;
    • How graphics can enhance your argument and increase your chances of winning;
    • Examples from major disputes from around the country.

    The agenda for the Patent Claim Construction workshop can be found here.  A complete brochure for this workshop, including an agenda, list of speakers, and registration form can be downloaded here.

    LSI - Law Seminars International - blue The registration fee is $347.50 for students and new employees,$545 for government employees, or $695 for all other attendees. Those interested in registering for the workshop can do so here, by calling 1-800-854-8009, or by faxing a registration form to 1-206-567-5058.

  • Practising Law Institute (PLI) #1 Practising Law Institute (PLI) will be holding a conference entitled: "Advanced Patent Prosecution Workshop 2008: Claim Drafting & Amendment Writing" on July 24-25, 2008 in New York, NY and on August 11-12, 2008 in San Francisco, CA.  The conference will offer presentations on the following topics:

    • Ethics for Patent Prosecutors
    • On-Sale Bar
    • Advanced Claim Drafting Issues
    • Recent Patent Law Developments
    • Claim Drafting Workshops – including a Biology/Chemistry breakout group
    • Duty of Disclosure
    • Examiner Interviews
    • Post Final Practice
    • Affidavit Practice
    • Amendment Workshops – including a Biology/Chemistry breakout group

    A full program for the Advanced Patent Licensing conference can be found here (New York) and here (San Francisco).  The registration fee for the conference is $1,495. Those interested in registering for the conference can do so here (New York) or here (San Francisco).

  •     By Donald Zuhn

    Pfizer
    On Wednesday, Pfizer announced that it had received a Notice of Intent to Issue an Ex Parte Reexamination Certificate for U.S. Patent No. 4,681,893 from the U.S. Patent and Trademark Office.  The ‘893 patent, which expires in March 2010, is directed in part to atorvastatin, the active ingredient in Pfizer’s cholesterol-reducing drug Lipitor®.  Pfizer noted that "it is pleased with the decision, which affirms the company’s position that the patent was properly granted."

    Ranbaxy
    The reexamination request (Reexamination No. 90/008,727) was filed by Ranbaxy Laboratories Ltd. in July 2007.  Ranbaxy had sought reexamination of the ‘893 patent after waging an unsuccessful battle to invalidate the patent in federal court; in August 2006, the Federal Circuit affirmed a District Court finding that Ranbaxy had infringed the ‘893 patent (while also reversing the District Court and finding another Pfizer atorvastatin patent, U.S. Patent No 5,273,995, invalid).

    In the Notice of Intent’s Statement of Reasons for Patentability and/or Confirmation, the Examiner indicated that Pfizer had overcome obviousness rejections based on European Publication No. EP 0 179 559 and U.S. Patent No. 4,647,576.  With respect to the ‘559 publication, Pfizer submitted a Declaration establishing that the ‘559 publication has the same inventor as the ‘893 patent, is therefore not by "another," and as a result is no longer available as prior art under 35 U.S.C. § 102(a).  With respect to the ‘576 patent, the Examiner determined that neither the ‘576 patent, nor any of the other prior art cited by Ranbaxy, would have led a chemist to substitute the carboalkoxy of the closest prior art compound (described in the ‘576 patent) with the carboxamide of atorvastatin of the ‘893 patent.  Quoting Takeda Chem. Indus., Ltd. v. Alphapharm Pty., Ltd., the Examiner noted that "in cases involving new chemical compounds, it remains necessary to identify some reason that would have led a chemist to modify a known compound in a particular manner to establish prima facie obviousness of a new claimed compound."  With respect to the reexamination of the ‘893 patent, the Examiner determined that no such reason existed.

    A second request for ex parte reexamination (Reexamination No. 90/009,048) filed by Ranbaxy on February 22, 2008 was denied by the Patent Office on April 9, 2008.

  •     By Kevin E. Noonan

    New_york_times
    The penchant for The New York Times‘ anti-innovation editorial policies to seamlessly blend into its "news" coverage (particularly on the Business page) has been noted by Patent Docs before.  Whether the latest example is more egregious than in the past is a matter of debate, but with apologies to President Reagan, "There they go again" in a piece published today under Robert Pear’s byline on page 1 of the Business section (see "Patent Law Battle a Boon to Lobbyists").

    The article goes wrong from the first sentence.  In writing about the fate of S. 1145, a bill with seventeen sections that proposes to modify U.S. patent law extensively (as previously reported by Patent Docs), Mr. Pear chose to bias the piece against patent stakeholders objecting to the bill:

    A fight has erupted in Congress over whether drug makers and other companies should be allowed to keep patents they obtained by misrepresentation or cheating.

    As Patent Docs readers know, this is not the issue, and "drug makers and other companies" are not trying to keep patents "obtained by misrepresentation or cheating."  Even ignoring that the issues with S. 1145 are more complicated than Mr. Pear recognizes, a fair statement of the inequitable conduct provisions of the bill is that they address the way courts determine if a patent was "obtained by misrepresentation or cheating."

    Armitage_robert
    Later in the piece, Mr. Pear acknowledges that the problem the bill proposes to address, inequitable conduct, has become "a plague on the patent system," pled in almost every patent case and arguably subject to abuse through ex post facto argument and occasional fanciful reconstruction of events.  Mr. Pear cited Robert Armitage (at left) of Eli Lilly and Company, that a finding of inequitable conduct is "like imposing the death penalty for relatively minor acts of misconduct."  He then misstates the position of innovator companies by asserting that "[b]rand-name drug companies are urging Congress to eliminate the penalty," which is not the case at all.

    Teva_1
    Of course, generics companies are more than happy to put their own spin, unquestioned, into the article.  Debra S. Barrett, a vice president of Teva Pharmaceuticals USA, is quoted as saying the changes supported by U.S. innovator companies "would make it easier for them to cheat and get away with it, easier for them to defend their patents and more difficult for us to get generic products onto the market in a timely way."  And the economics of the current drug regime are invoked, Mr. Pear citing the desire of AARP and other "consumer groups" to obtain generic drugs at prices "30 percent to 80 percent less than the equivalent brand-name drugs."  (There is nothing in the piece, of course, regarding the relative development costs between innovator and generic drug companies.)

    Even then, Mr. Pear misses the point.  He states that "[i]n the last 15 years, the United States Court of Appeals for the Federal Circuit, which handles patent cases, has affirmed findings of inequitable conduct in at least 40 cases, including 14 that involved pharmaceutical or health care products."  But in view of the frequency with which inequitable conduct is alleged, the real story here is how infrequently inequitable conduct is found.  Showing an inability or unwillingness to do the necessary research (or, to be fair, the limitations of tight deadlines), Mr. Pear gins up his numbers by stating "[s]imilar findings have been issued by federal district judges in an unknown number of cases that were not appealed."

    Unknown to Mr. Pear, perhaps, but not unknowable.  (A review of the Times list of Mr. Pear’s recent articles reveals he is a reporter on general subjects, without any particular slant to business or technology stories.)  A Lexis search reveals that while inequitable conduct was alleged in over 2,100 patent cases between 1993 and 2008, accused infringers asserting inequitable conduct rarely prevailed.  And to complete the picture, while the Federal Circuit has affirmed inequitable conduct in 40 cases since 1993, it has not upheld inequitable conduct findings in 379 other cases.  These statistics bear our Judge Nichols’ admonition twenty years ago in Burlington Indus., Inc. v. Dayco Corp., 849 F.2d 1418, 1422 (Fed. Cir. 1988), and recounted in the article as Congressional testimony from the Biotechnology Industry Organization, that the charge of inequitable conduct is a "plague on the patent system" that needs rectifying.  And ironically, the position advocated in the article is contrary to the results of a study done by Robert Shapiro, who concluded that the inequitable conduct provisions of S. 1145 would increase the frequency of inequitable conduct challenges (see "BIO CEO Provides Update on Patent Reform and Follow-on Biologics Legislation – Part I").

    Greenwood_jim
    Balance, to the extent there is any, can be found in the middle of the article, where James C. Greenwood (at left) from the Biotechnology Industry Organization; Robert Armitage; and Harry F. Manbeck Jr., Commissioner of Patents and Trademarks under President George H.W. Bush explain the competing influences between disclosing relevant information and trying to avoid inequitable conduct allegations by submitting to the Patent Office all the information that might be considered relevant to patentability.  Quoting Mr. Greenwood, "[t]he poor patent examiner gets a dump truck full of information that he has to pore over without any assistance from the applicant" under the current scheme, which would be modified under S. 1145 to try to avoid this situation.

    Dudas_jon
    All evidence of balance rapidly disappears, however, when Mr. Pear reports the contribution of Jon Dudas (at right), Undersecretary of Commerce for Intellectual Property.  Ostensibly tying the propensity to overdisclose less-than-relevant information to the backlog of unexamined patents, Mr. Dudas ignores the inequitable conduct issue entirely, alleging instead that "[w]e [the Patent Office] are getting more and more unpatentable ideas, worse and worse quality applications."  His "evidence":  falling allowance rates, which the cognoscenti will recognize are the result of changing examination standards (i.e., recalcitrance to patent allowances under the Dudas administration compared with cooperation with patent applicants under the Lehman administration).  Even if Mr. Dudas were correct, his evidence is the solution:  don’t grant patents to applicants submitting unpatentable ideas or poor quality applications.

    Only towards the end of the article does Mr. Pear discuss the purported subject of the piece:  how interest groups have spent millions lobbying Congress for or against S. 1145 (and the companion House bill, H.R. 1908, which passed last September).  At least Mr. Pear properly identifies the players:  the so-called Coalition for Patent Fairness, comprised of "high technology" companies like Intel and Cisco (not mentioned are the activities of Cisco’s own Patent Troll tracker blogger, who tried to influence the debate more cost-effectively), and on the other side, the Coalition for 21st Century Patent Reform, whose members include several pharmaceutical and biotechnology companies.  Even in identifying these groups, Mr. Pear (and the Times) bias shines through:  while the motivations of "Patent Fairness" group are said to be to avoid "disputes [that] drain resources that could be better spent on research and innovation," the pharmaceutical companies "zealously guard their intellectual property and are more likely to file suit to protect their patents."  Mr. Pear either doesn’t understand, or won’t admit, that the reasons for the groups’ different positions on patents and their value are directly linked to differences in development costs and obsolescence horizons between "high" tech companies (who can be tripped up by a clever teenager with a computer, a modem, and a good idea for a new Internet applet for social networking) and biotech/pharma companies, who face development and regulatory costs in the several hundreds of millions of dollars to get a new drug to market.  These differences have real consequences to the companies on either side of the debate.

    What the Times doesn’t consider, or refuses to mention, is that there will be consequences for the rest of us as well.  Will the American public be happy with an outcome that increases the number and decreases the costs of the newest electronic gadget, while at the same time decreasing the number of new drugs, especially biologic drugs that promise to address, for the first time, heretofore untreatable diseases?  It would be refreshing if the Times honestly set out what’s really at stake in the debate over S. 1145.

  •     By Donald Zuhn

    Neuralstem
    On Monday, Neuralstem, Inc. announced that the European Patent Office had granted European Patent No. EP 0 915 968 to the Rockville, Maryland-based biotech company.  The ‘968 patent, entitled, "Isolation, Propagation and Directed Differentiation of Stem Cells from Embryonic and Adult Central Nervous System of Mammals," is directed to methods of expanding, culturing, and differentiating mammalian central nervous system stem cells in vitro; in vitro mammalian central nervous system (CNS) stem cell cultures produced from such methods; methods of generating mature neurons from mammalian multipotential CNS stem cells; and mature neurons generated from such methods.  According to Neuralstem’s press release, the European patent has been validated in France, Germany, Ireland, Spain, Sweden, Switzerland, and the United Kingdom.

    Neuralstem’s technology allows for the production of commercial quantities of neural stem cells from the human brain and spinal cord, and for the differentiation of such cells into mature, physiologically relevant human neurons and glia.  Neuralstem is utilizing this technology to treat diseases of the major central nervous system, including ischemic paraplegia, traumatic spinal cord injury, and ALS (Lou Gehrig’s disease).  According to Neuralstem’s website, the company’s technology has been used to extend the life of rats with ALS, as well as to reverse paralysis in rats with ischemic spastic paraplegia.

    Stemcells
    Neuralstem CEO Richard Garr called the ‘968 patent a "core technology patent," adding that "the European Patent Office has now joined with the U.S. Patent Office in rejecting any arguments that the body of Stem Cells Inc. patents and publications, noted in the [European] examinations, in any way prevents Neuralstem’s patents from issuing."  As we reported last week, StemCells, Inc. filed a patent infringement suit against Neuralstem, asserting that Neuralstem had infringed four of StemCells’ U.S. patents (see "StemCells’ Patents Survive Reexam — StemCells and Neuralstem Differ on Extent of Changes").  Neuralstem countered by seeking a reexamination of the asserted patents, and earlier this month, StemCells announced that the Patent Office had "upheld" two of the patents with "only minor amendments."  Neuralstem released its own statement, contending that StemCells had "completely mischaracterized the meaning of the US Patent and Trademark Office’s most recent action."  While Mr. Garr’s comments suggest that Neuralstem believes it has the better argument in its ongoing patent dispute with StemCells, StemCells has indicated that it plans to move forward with the case.

    Independent claims 1, 6, 14, 17, and 24 of the ‘968 patent recite:

    1.  A method for expansion and long-term culture in vitro of stem cells of the central nervous system of a mammal, wherein the stem cells maintain the multipotential capacity to differentiate into neurons, astrocytes, and oligodendrocytes, comprising the steps of:
        a) dissociating cells from central nervous system tissue by mechanical trituration;
        b) culturing the dissociated cells adhered onto a plate in a chemically defined serumfree culture medium;
        c) plating dissociated cells at a density not exceeding 20,000 cells/cm2 and, in subsequent passages, replating the cultured cells at a density not exceeding 10,000 cells/cm2;
        d) adding daily to the cultured cells a growth factor selected from the group consisting of
            i) bFGF at a concentration of at least 10 ng/ml,
            ii) EGF at a concentration of at least 10 ng/ml,
            iii) TGF-alpha at a concentration of at least 10 ng/ml, and
            iv) aFGF at a concentration of at least 10 ng/ml plus 1yg/ml heparin;
        e) replacing the culture medium with fresh medium within every two days;
        f) passaging the cultured cells within four days after plating so as not to exceed 50% confluence; and
        g) passaging the cultured cells by treating the cultured cells with saline solution and scraping cells from the plate.

    6.  An in vitro culture of stem cells of the central nervous system of a mammal, wherein the stem cells maintain the multipotential capacity to differentiate into neurons, astrocytes, and oligodendrocytes.

    14.  A method for differentiation of an in vitro culture of stem cells of the central nervous system of a mammal, wherein the stem cells maintain the multipotential capacity to differentiate into neurons, astrocytes, and oligodendrocytes, comprising the steps of:
        a) dissociating cells from central nervous system tissue by mechanical trituration;
        b) culturing the dissociated cells on a plate in complete absence of serum;
        c) adding daily to the cultured cells a first growth factor selected from the group consisting of
            i) bFGF at a concentration of at least 10 ng/ml,
            ii) EGF at a concentration of at least 10 ng/ml,
            iii) TGF-alpha at a concentration of at least 10 ng/ml, and
            iv) aFGF at a concentration of at least 10 ng/ml plus 1Hg/ml heparin;
        d) passaging the cultured cells by treating the cultured cells with saline solution and scraping the cells from the plate; and
        e) removing the first growth factor from the cultured cells.

    17.  A method for in vitro generation of region-specific, terminally differentiated, mature neurons from cultures of mammalian multipotential
    CNS stem cells, comprising the steps of:
        a) culturing multipotential CNS stem cells from a specific region in a chemically defined serum-free culture medium containing a growth factor;
        b) replacing the medium with growth factor-free medium;
        c) harvesting the stem cells by trypsinization;
        d) plating the stem cells at a density of between 100,000 to 250,000 cells per square centimeter; and
        e) culturing the cells in a glutamic acid-free chemically defined serum-free culture medium.

    24.  An in vitro culture of region-specific, terminally differentiated, mature neurons derived from cultures of mammalian multipotential CNS stem cells from a specific region.