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  • Another Look at IPO Top 300 and Life Sciences Top 53

    By Donald Zuhn —

    IPO #2Last week, we reported on the release of the Intellectual Property Owners Association's (IPO) list of the Top 300 organizations receiving U.S. patents in 2011 (see "IPO Releases List of Top 300 Patent Holders for 2011").  As in past years, Patent Docs used the IPO's list of top patent holders to compile a list of the top 53 life sciences companies and organizations receiving U.S. patents in 2011.  Our analysis was not quite an exact science, as we noted that a number of companies and organizations appearing on the Life Sciences Top 53 are likely to be involved in work outside the life sciences sector, and therefore, that a portion of the patents granted to these companies and organizations are likely to be directed to other than life sciences-related inventions.

    Wegner, HaroldIn a series of e-mail newsletters distributed last week, Hal Wegner (at left) reported on the IPO's Top 300 list, noting that the IPO's list was dominated by the electronics/software/manufacturing sectors, which grabbed the top ten spots on the list, and that the top ten bio/pharma companies averaged 288 patents, or "less than one-sixth that of the patent industry leaders."  In comparing his own analysis with our Life Sciences Top 53, Mr. Wegner noted that our list was compiled using a broader definition of life sciences and his list resulted from a narrower focus on pharmaceuticals.  In a follow-up e-mail, Mr. Wegner observed that "[t]he Top Ten pharma companies of the world average $35 billion in patent-secured sales, the most profitable use of the patent system amongst all industries."

    To get a more accurate picture of the top companies involved in bio/pharma patenting, we searched the U.S. Patent and Trademark Full-Text and Image Database for the number bio/pharma patents that were issued last year to each of the companies and organizations on our Life Sciences Top 53.  The number of bio/pharma patents was determined by searching for patents designated as belonging to at least on of the following classes:  424 (Drug, Bio-Affecting and Body Treating Compositions), 435 (Chemistry: Molecular Biology and Microbiology), 436 (Chemistry: Analytical and Immunological Testing), 504 (Plant Protecting and Regulating Compositions), 506 (Combinatorial Chemistry Technology: Method, Library, Apparatus), and/or 514 (Drug, Bio-Affecting and Body Treating Compositions) that issued in the specified year.  A search of the USPTO patent database for 2011 patents designated as belonging to one of the above classes indicates that of the 244,430 utility patents that were issued last year, 14,973 (6.1%) were directed to bio/pharma-related inventions.

    After performing the above search for each of the companies and organizations on our Life Sciences Top 53, we obtained the following results (with bio/pharma patents — i.e., those designating at least one of the above classes — listed in the "Bio/Pharma Patents" column; click on table to enlarge):

    Table 1
    As indicated above, the Life Sciences Top 53 secured a total of 11,681 patents, of which 3,059 (26.2%) were bio/pharma patents.  Re-sorting the Life Sciences Top 53 by bio/pharma patents produced the following list (click on table to enlarge):

    Table 2
    While each of the Top 10 bio/pharma companies and organizations from our LIfe Sciences Top 53 secured at least 100 bio/pharma patents in 2011, the 1,578 patents granted to the Bio/Pharma Top 10 constituted just over one-fourth of the number of patents issued to IBM in 2011 (IBM took the top spot on the IPO Top 300 list with 6,148 patents).

    While our search produced a list that may be more indicative of the top bio/pharma patentees (at least among the top 300 patentees), it was probably limited in some respects.  For example, to the extent that bio/pharma patents were designated in some other class, such patents would have been omitted from our count.  In addition, to the extent that a subsidiary of a given company contributed to that company's patent count and the subsidiary had a distinct name, such patents would have been omitted from our count (the IPO notes that for its Top 300 list, patents in the name of a majority-owned company were included with patents of the parent organization if the organization asked the IPO to include subsidiaries).  Moreover, if the assignee was not indicated on the face of the patent, that patent would have been omitted from our count.  That being said, the IPO notes that for its Top 300 list, patents that were granted to two or more organizations jointly were attributed to the organization listed first on the patent document.  In generating our list, such patents would have been included in both organizations' counts (this difference may explain why Monsanto was named as an assignee on 266 bio/pharma patents, but appears to have been granted only 234 patents on the IPO's list).

  • Plaintiffs Respond to Myriad’s “Suggestion” of Mootness or, Alternatively, Motion for Remand in AMP v. USPTO

    By Kevin E. Noonan —

    MyriadOn May 30th, Myriad Genetics filed a motion in the remand of Association for Molecular Pathology v. U.S. Patent and Trademark Office case ("Myriad") to the Federal Circuit, styled "Appellant's Suggestion of Mootness, or, in the alternative, Motion to Remand," to address the fundamental question of whether the Federal Circuit, or any U.S. court, has jurisdiction to hear the case.  This issue is based on the Federal Circuit's determination, in its now-vacated decision, that only one plaintiff, Dr. Harry Ostrer, had standing to bring the lawsuit, coupled with Myriad's contention that the basis for jurisdiction was abolished when Dr. Ostrer changed his academic affiliation.  This issue was brought to the Court's attention two days before it handed down its now-vacated decision, and was not sufficient to induce the Federal Circuit to rehear the case either before the original panel or en banc.  After remand from the Supreme Court's decision granting certiorari and vacating the Federal Circuit's opinion for reconsideration in view of the Court's Mayo v. Prometheus decision, the Federal Circuit did not include this issue in the questions to be addressed by the parties or interested amici.

    ACLUPlaintiffs have responded in a brief that contains three arguments.  The first is that Dr. Ostrer was sued personally, so that his change in employment status is not relevant to the standing issue.  This argument is factual in nature, alleging that Dr. Ostrer remains capable of performing BRCA genetic testing in his new position at Albert Einstein College of Medicine/Montefiore Hospital but has not done so due to Myriad's threat of patent infringement liability.  The brief challenges Myriad's contention that the threat of infringement liability was directed to Dr. Ostrer's prior employer, New York University (NYU), because Myriad's "threatening" letter was directed towards Dr. Ostrer personally and NYU was not named as a plaintiff in the lawsuit.  (While it is true that the letter was addressed to Dr. Ostrer, the brief notes that Myriad in fact sued the employer of two other putative plaintiffs, Drs. Ganguly and Kazazian, and it should be remembered that the ACLU and PubPat, the sponsors of the litigation were responsible for what parties were named, not Myriad.)  The brief contends that finding his change of employment to have stripped Dr. Ostrer of standing could be contrary to the Court's original finding that he had standing as an individual; this argument does not address Myriad's position that regardless of his subjective intent of being "ready" and "willing" to infringe he would only be "able" to do so if Montefiore Hospital permits him to be.  In this regard, the brief states that Myriad's citation to the Montefiore Hospital website as evidence that Dr. Ostrer's is not unable to provide BRCA genetic testing services is "outdated" and provides an updated citation (Laboratory Services, Montefiore Medical Center).  Finally, the brief resists the suggestion that the Court remand to the District Court for a factual determination of the standing issue, stating that such action would be appropriate only if Myriad were to make an adequate proffer regarding a change in Dr. Ostrer's ability to infringe, which (of course) the brief contends Myriad has not done.

    PUBPATPlaintiffs' second argument is that, even under the standard enunciated by the Federal Circuit in its now-vacated decision, other plaintiffs, including Ms. Reich and Ms. Matloff also have standing, being themselves "personally" threatened with suit.  Ms. Reich is an NYU employee, and Ms. Matloff works at Yale.  The brief argues that, insofar as the Court's earlier decision is read as holding that standing is predicated on the ability to perform BCRA testing, then Ms. Reich's continued employment at NYU confers standing upon her.  This argument does not address whether Ms. Reich has the professional capacity to perform BRCA testing in a milieu other than a lab (Dr Ostrer's) where the testing can be performed, a concern that echoes Myriad's argument (unrebutted in Plaintiffs' brief) that Dr Ostrer no longer has standing because Montefiore does not have regulatory approval (from New York State, for example) to perform the tests.  As for Ms. Matloff, Myriad's "threat" was conveyed not by a formal letter (as were the "threats" to Dr. Ostrer at NYU and Drs. Ganguly and Kazazian at Penn) but in a telephone call initiated by Ms. Matloff; it can reasonably be assumed that the call was for the express intent to garner the "threat" and create standing, a tactic that can only kindly be said should not be encouraged.

    The final (and most lengthy) argument advanced by Plaintiffs is that the Federal Circuit erred with regard to the other named plaintiffs, who according to the brief also have standing.  The brief specifically addresses this argument to one organizational plaintiff, the American College of Medical Genetics and Genomics (formerly, the American College of Medical Genetics), reiterating its position that standing should lie because "gene patenting is germane to ACMG's purpose."  These plaintiffs have organizational standing, according to the brief, under Warth v. Seldin, 422 U.S. 490, 511 (1975).  As for the other plaintiffs, the brief takes the opportunity to renew its attack on the standing standards imposed by the Federal Circuit, which Plaintiffs contend are "more stringent" than the "reasonable apprehension of suit" test abrogated (in a footnote) in the Supreme Court's MedImmune, Inc. v. Genentech, Inc. decision.  549 U.S. 118, 127 (2007).  The brief characterizes what it fashions the "personally threatened" test as being a "bright line rule" that the Supreme Court "instruct[ed] [in MedImmune] are inappropriate when analyzing a plaintiff's standing in a declaratory judgment action."  The brief supports this assertion by citing a portion of the earlier, now-vacated Federal Circuit decision, where the Court found that "every other similarly situated researcher and institution" ceased BRCA testing as the result of Myriad's patent enforcement actions, that there was no evidence that any other researcher or institution had successfully challenged Myriad's assertion of its patent rights, nor was there evidence that Myriad's intention to assert those rights had changed.  This pattern should be enough to make Myriad's actions sufficiently "proximate" to raise standing, according to Plaintiffs.  The brief also cites several cases where the Supreme Court and other appellate courts (including the Federal Circuit) have found standing without direct action against individual plaintiffs, including Doe v. Bolton, 410 U.S. 179, 188 (1973); Virginia v. Am. Booksellers Ass'n, Inc., 484 U.S. 383, 393 (1988); Vt. Right to Life Comm., Inc. v. Sorrell, 221 F.3d 376, 382 (2d Cir. 2000); and Biotech. Indus. Org. v. District of Columbia, 496 F.3d 1362, 1370 (Fed. Cir. 2007).  However, these were all cases involving government action in enforcing a statute.  The brief recognizes this, but calls it a "difference without a distinction" (seemingly contrary to similar distinctions made by Justice Scalia in the MedImmune opinion and garbling in the process Learned Hand's famous aphorism).  According to the brief, "[t]he elements required for Article III standing do not differ based on the public or private nature of the potential enforcer.  A party can show a substantial controversy based on impending injury resulting from an invalid law or patent.  A requirement that the law or patent be enforced against a party before they can seek judicial alleviation of that injury is contrary to the law."  The brief provides no legal basis for equating a statute with a patent or government with private action.

    Opening party briefs and briefs by any amici remain due on June 15th.

  • Court Report

    By Sherri Oslick —

    Gavel About Court Report:  Each week we will report briefly on recently filed biotech and pharma cases.

    Fidopharm Inc. v. Merial Ltd.
    1:12-cv-00714; filed June 5, 2012 in the District Court of Delaware

    Declaratory judgment of non-infringement and invalidity of U.S. Patent No. 6,096,329 ("Insecticidal Combination to Control Mammal Fleas, in Particular Fleas on Cats and Dogs," issued August 1, 2000), licensed to Merial in the animal health field, based on plaintiffs' manufacture and impending sale of its newly formulated PetArmor® Plus flea-and-tick products for cats and dogs.  View the complaint here.


    Merial Ltd. et al. v. VELCERA Inc. et al.
    3:12-cv-00075; filed June 5, 2012 in the Middle District of Georgia

    • Plaintiffs:  Merial Ltd.; Merial SAS
    • Defendants:  Velcera Inc.; Fidopharm Inc.

    Infringement of U.S. Patent No. 6,096,329 ("Insecticidal Combination to Control Mammal Fleas, in Particular Fleas on Cats and Dogs," issued August 1, 2000), licensed to Merial in the animal health field, based on defendants' manufacture and impending sale of its newly formulated PetArmor® Plus flea-and-tick products for cats and dogs.  View the complaint here.


    Medicis Pharmaceutical Corp. v. Zydus Pharmaceuticals USA, Inc. et al.
    3:12-cv-03368; filed June 5, 2012 in the District Court of New Jersey

    • Plaintiff:  Medicis Pharmaceutical Corp.
    • Defendants:  Zydus Pharmaceuticals USA Inc.; Cadila Healthcare Ltd.

    Medicis Pharmaceutical Corp. v. Zydus Pharmaceuticals USA Inc. et al.
    1:12-cv-00707; filed June 4, 2012 in the District Court of Delaware

    • Plaintiff:  Medicis Pharmaceutical Corp.
    • Defendants:  Zydus Pharmaceuticals USA Inc.; Cadila Healthcare Ltd.

    The complaints in these cases are substantially identical.  Infringement of U.S. Patent Nos. 5,908,838 ("Method for the Treatment of Acne," issued June 1, 1999) and 7,790,705 ("Minocycline Oral Dosage Forms for the Treatment of Acne," issued September 7, 2010) following a Paragraph IV certification as part of Zydus' filing of an ANDA to manufacture a generic version of Medics' Solodyn® (minocycline hydrochloride extended release tablets, used to treat acne).  View the Delaware complaint here.


    Abbott Laboratories et al. v. Kremers Urban Pharmaceuticals Inc.
    1:12-cv-00703; filed June 1, 2012 in the District Court of Delaware

    • Plaintiffs:  Abbott Laboratories; Abbott Respiratory LLC
    • Defendant:  Kremers Urban Pharmaceuticals Inc.

    Infringement of U.S. Patent Nos. 6,080,428 ("Nicotinic Acid Compositions for Treating Hyperlipidemia and Related Methods Therefor," issued June 27, 2000) and 6,469,035 ("Methods of Pretreating Hyperlipidemic Individuals with a Flush Inhibiting Agent Prior to the Start of Single Daily Dose Nicotinic Acid Therapy to Reduce Flushing Provoked by Nicotinic Acid," issued October 22, 2002) following a Paragraph IV certification as part of Kremers' filing of an ANDA to manufacture a generic version of Abbott's Niaspan® (niacin extended-release tablets, used to treat hypercholesterolemia).  View the complaint here.


    Merck Sharp & Dohme Corp. v. Accord Healthcare, Inc. USA et al.
    3:12-cv-03324; filed June 1, 2012 in the District Court of New Jersey

    • Plaintiff:  Merck Sharp & Dohme Corp.
    • Defendants:  Accord Healthcare, Inc. USA; Accord Healthcare, Inc.; Intas Pharmaceuticals Ltd.

    Merck Sharp & Dohme Corp. v. Sandoz Inc.
    3:12-cv-03289; filed May 31, 2012 in the District Court of New Jersey

    • Plaintiff:  Merck Sharp & Dohme Corp.
    • Defendant:  Sandoz Inc.

    The complaints in these cases are substantially identical.  Infringement of U.S. Patent Nos. 5,691,336 ("Morpholine Compounds Are Prodrugs Useful As Tachykinin Receptor Antagonists," issued November 25, 1997) and 5,716,942 ("Treatment of Migraine With Morpholine Tachykinin Receptor Antagonists," issued February 10, 1998) following a Paragraph IV certification as part of Sandoz's filing of an ANDA to manufacture a generic version of Merck's Emend® (fosaprepitant dimeglumine for injection, used in the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy including high-dose cisplatin, and to prevent nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy).  View the Sandoz complaint here.


    Human Genome Sciences, Inc. v. Kappos
    1:12-cv-00607; filed June 1, 2012 in the Eastern District of Virginia

    Review and correction of the patent term adjustment calculation made by the U.S. Patent and Trademark Office for U.S. Patent No. 8,071,092 ("Methods of Inhibiting B Lymphocytes Using Antibodies to Neutrokine-alpha," issued December 6, 2011).  View the complaint here.

  • Conference & CLE Calendar

    Calendar

    June 13-15, 2012 – Fundamentals of Patent Prosecution 2012: A Boot Camp for Claim Drafting & Amendment Writing (Practising Law Institute) – New York, NY

    June 14, 2012 – The Elimination and Creation of Defenses in the Wake of AIA (Technology Transfer Tactics) – 1:00 – 2:00 pm (Eastern)

    June 18-21, 2012 – BIO International Convention (Biotechnology Industry Organization) – Boston, MA

    June 20-21, 2012 – International Forum on Pharma Patent Lifecycles*** (C5) – London, England

    July 23-24, 2012 – Patent Cooperation Treaty Seminar (American Intellectual Property Law Association) – Alexandria, VA

    June 24-26, 2012 – IP Business Congress (Intellectual Asset Management (IAM) magazine) – Cascais, Portugal

    June 25-26, 2012 – Hatch-Waxman Boot Camp*** (American Conference Institute) – San Diego, CA

    July 11-13, 2012 – Fundamentals of Patent Prosecution 2012: A Boot Camp for Claim Drafting & Amendment Writing (Practising Law Institute) – San Francisco, CA

    July 12, 2012 – Inducement to Infringe in Hatch-Waxman Litigation:  Lessons from Bayer Schering v. Lupin and AstraZeneca v. Apotex for Pharma Patents (Strafford) – 1:00 – 2:30 pm (EDT)

    July 17-19, 2012 – Product and Pipeline Enhancement for Generics*** (marcus evans) – Washington, DC

    July 30-31, 2012 – Freedom to Operate*** (American Conference Institute) – Philadelphia, PA

    July 30 to August 1, 2012 – Intensive Patent Law Seminar (Chisum Patent Academy) – Seattle, WA

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

  • Webinar on Inducement to Infringe in Hatch-Waxman Litigation

    Strafford #1Strafford will be offering a webinar/teleconference entitled "Inducement to Infringe in Hatch-Waxman Litigation:  Lessons from Bayer Schering v. Lupin and AstraZeneca v. Apotex for Pharma Patents" on July 12, 2012 from 1:00 – 2:30 pm (EDT).  Thomas L. Irving and David P. Frazier, Ph.D. of Finnegan Henderson Farabow Garrett & Dunner will provide guidance on claim and label language; to proactively coordinate patent, regulatory and clinical personnel; and to maintain consistency between claims and likely or actual label language throughout patent prosecution and label negotiation with the FDA.  The webinar will review the following questions:

    • What can be learned from the AstraZeneca v. Apotex and the Bayer Schering v. Lupin decisions?
    • What are the best approaches to maintain consistency between claims and likely or actual label language?
    • What steps can be taken to maintain the coordination of patent, regulatory and clinical personnel throughout the patent prosecution and label negotiation with FDA?

    An interactive Q&A session will follow the presentation.

    The registration fee for the webinar is $297 ($362 for registration and CLE processing).  Those registering by June 22, 2012 will receive a $50 discount.  Those interested in registering for the webinar, can do so here.

  • IPO Releases List of Top 300 Patent Holders for 2011

    Life Sciences Top 50 (plus 3)

    By Donald Zuhn —

    IPO #2On Wednesday, the Intellectual Property Owners Association (IPO) released its 29th annual list of the top 300 organizations receiving U.S. patents.  Patent Docs Readers may recall that the U.S. Patent and Trademark Office stopped releasing its annual list of top patent recipients in 2006 in order to "discourag[e] any perception that we believe more is better."

    The IPO compiled its list by counting the number of utility patents granted during 2011 that listed an organization or a subsidiary as the owner on the printed patent.  The IPO noted that if an assignment to an organization or its subsidiary was recorded after the patent was printed, the patent was not counted, and further, that patents which were granted to two or more organizations jointly were attributed to the organization listed first on the patent.  The IPO also noted that 244,430 patents were issued in 2011, which was an increase from the 233,127 patents that issued in 2010.  The top fifteen companies on the IPO Top 300 are listed below (click on table to expand):

    IPO Top 15
    Falling out of the Top 15 in 2011 was Intel Corp., which dropped to 17th.

    As in past years, Patent Docs used the IPO's list of top patent holders to compile a list of the top life sciences companies and organizations receiving U.S. patents in 2011.  In the past six years, the number of life sciences companies and organizations making the list has gone from 51 in 2006 to 47 in 2007, 43 in 2008, 47 in 2009, 56 in 2010, and 53 last year.  Each organization's IPO top 300 ranking for 2011 is indicated in the "2011 IPO Rank" column; the IPO top 300 ranking for 2010 (if available) is indicated in the "2010 IPO Rank" column; and the change in number of patents from 2010 is indicated in "+/- from 2010."  The Life Sciences Top 50 (plus 3) is listed below (click on table to expand):

    Biotech Top 53
    Life sciences companies and organizations that failed to make the IPO top 300 in 2011 after making it in 2010 included Boehringer Ingelheim International GmbH (#260 on the IPO top 300 for 2010), Becton, Dickinson and Co. (263), Columbia University (272), Vertex Pharmaceuticals, Inc. (274), University of Pennsylvania (289), Unilever Patent Group (296), Ajinomoto Co., Inc. (297), Cornell Research Foundation Inc. (298), and University of Washington (301).  Cardiac Pacemakers, Inc. returned to the Top 300 after a one year hiatus.

    Please note that some of the companies and organizations listed above may be involved in work outside the life sciences sector, and therefore, a portion of the patents granted to these companies and organizations may be directed to other than life sciences-related inventions.  In addition, our list is a little inclusive in that we included medical device companies.

    For additional information regarding this topic, please see:

    • "IPO Releases List of Top 300 Patent Holders for 2010," June 30, 2011
    • "IPO Releases List of Top 300 Patent Holders for 2009," May 26, 2010
    • "IPO Releases List of Top 300 Patent Holders for 2008," May 14, 2009
    • "IPO Releases List of Top 300 Patent Holders," May 22, 2008
    • "IPO Posts List of Top 300 Patent Holders," April 20, 2007

  • Tomato Genome Determined

    By Kevin E. Noonan —

    CoverHans Sauer, Associate General Counsel for Intellectual Property for the Biotechnology Industry Organization (BIO), frequently asks (when discussing patent-eligibility of genes):  "What about cucumber genes?  Should they be patented?"  If Hans wishes to remain au courant, however, he will need to update this question by asking "What about tomato genes?" after the disclosure, in this week's Nature, that the entire genomic DNA sequence of the tomato (Solanum lycopersicum) has been deciphered (The Tomato Genome Consortium, "The tomato genome sequence provides insights into fleshy fruit evolution," Nature 485: 635–41 (31 May 2012)).

    As with other species genome project results, the reported sequence reveals interesting relationships between tomatoes and closely-related species (like the potato, Solanum tuberosum), including "wild" species (Solanum pimpinellifolium) related to the domestic tomato, as well as identifying sequence characteristics resulting from evolutionary events in the tomato pedigree.

    Heinz-ketchupThe researchers used an inbred cultivar, "Heinz 1706," having a "predictive" genome size of 900Mb on 12 tomato chromosomes.  The tomato genomic sequence was compared with the "wild" tomato sequence as well as other domesticated species of Solanum (particularly potato).  The sequence differences between the domesticated and wild tomato amounted to 0.6% nucleotide divergence in 5.4 million single nucleotide polymorphisms (SNPs) scattered throughout the genome.

    Between tomato and potato, on the other hand, 8.7% sequence divergence was found, including nine large and several smaller inversions (which can facilitate sequence and species divergence by interfering with meiotic pairing), with intergenic and heterochromatic (repeat-rich) sequences showing (not unexpectedly) > 30% sequence divergence.

    Evolutionarily, the tomato sequence showed evidence of two consecutive genome triplications (a phenomenon common among plants but unknown for animal species), one recent between tomato and potato (~7.3 Myr ago), and one ancient (at about the rosid (tomato) – asterid (grape) divergence, ~71 +/- 19.4 Myr ago).  These events are believed to have provided the genetic plasticity to develop genes controlling fruit characteristics, such as color and "fleshiness."  These include transcription factors and enzymes involved in ethylene biosynthesis (used for ripening), red light photoreceptors (PHYB1/PHYB2), and lycopene synthesis (PST1/PSY2).  Interestingly, the researchers reported that "[s]everal cytochrome P450 subfamilies associated with toxic alkaloid biosynthesis show contraction or complete loss in tomato and the extant genes show negligible expression in ripe fruits," a genetic adaptation to be expected for plants that have adopted a seed-dispersal mechanism requiring that the fruit be eaten by animals and the seeds passed in their spoor.  Differential expression of genes for cell wall architecture was also observed and believed to be involved in this aspect of the tomato life cycle.

    On the other hand, the observed patterns comparing tomato genes with grape orthologs (22.5% of grape genes have an orthologous region in tomato, 39.9% have two and 21.6% have three) suggested that triplication was followed by "widespread gene loss" (see Figure 2 of publication).  Synteny maps between tomato chromosomes and chromosomes from potato, eggplant (aubergine), pepper, and tobacco were prepared and showed high levels of synteny, not unexpected in view of these species' interrelatedness.

    Turning to the overall chromosome structure, the tomato showed pericentric heterochromatin and distal euchromatin, with miRNA and chloroplast insertions "more evenly distributed" throughout euchromatin.  There was evidence of fewer high-copy LTR-containing retrotransposons in the tomato genome than in Sorghum or Arabidopsis genomes, with "older" average insertion age (2.8M v. 0.8M years ago); the tomato genome is "unusual among angiosperms by being largely comprise of low copy number DNA."  In view of these differences with Arabidopsis, it was paradoxical that "[c]hromosomal organization of  genes, transcripts, repeats and small RNAs (sRNAs) is very similar" between the tomato and Aribodopsis genomes.

    TomatoesSequence comparisions and open reading frame analyses found from 34,727 to 35,004 protein-coding genes in the tomato genome.  Of these, 18,320 were orthologs to potato genes; comparisons of synonymous vs. non-synonymous nucleotide substitution patterns between potato and tomato with similar comparisons between sorghum and maize (11.9Myr divergence) suggested stronger "diversifying" selection in the tomato/potato pair.  Comparison of the tomato genome with the "wild" S. pimpinellifolium species genes showed 7,378 identical genes and 11,753 genes with only synonymous nucleotide sequence changes; of the rest (12,629 genes), there were not only non-synomynous changes but also gain/loss of stop codons, with implications for gross changes in functionality.  In some instances, "several" chromosomal segments (particularly from cherry tomatoes) were more similar to the S. pimpinellifolium species than to the Heinz 1076 cultivar sequence.

    The tomato genome shares with the soybean and potato genomes the location of small, regulatory RNAs to "gene-rich" chromosomal regions and particularly promoters.  96 conserved miRNA species were identified in tomato compared with 120 such species in potato, grouped into 34 families (10 "highly conserved" in plants and the others "less conserved" that are more abundant in potato than tomato; some of these potato-specific miRNAs specifically target Toll interleukin receptor, nucleotide-binding site and leucine-rich repeat genes.  Protein-coding genes from tomato, potato, Arabidopsis, rice, and grape were "clustered" into 23,208 gene groups (having at least 2 members), of which "8,615 are common to all five genomes, 1,727 are confined to eudicots (tomato, potato, grape and Arabidopsis), and 727 are confined to plants with fleshy fruits (tomato, potato and grape)."

    The report concludes with these lessons from the genome that reflect the natural history of the tomato:

    The genome sequences of tomato and S. pimpinellifolium also provide a basis for understanding the bottlenecks that have narrowed tomato genetic diversity: the domestication of S. pimpinellifolium in the Americas, the export of a small number of genotypes to Europe in the 16th century, and the intensive breeding that followed.  Charles Rick pioneered the use of trait introgression from wild tomato relatives to increase genetic diversity of cultivated tomatoes.  Introgression lines exist for seven wild tomato species, including S. pimpinellifolium, in the background of cultivated tomato.  The genome sequences presented here and the availability of millions of SNPs will allow breeders to revisit this rich trait reservoir and identify domestication genes, providing biological knowledge and empowering biodiversity-based breeding.

    The genomic data generated by the whole project is available on-line, in GenBank under accession number AEKE00000000.  The individual chromosome sequences as numbers CM001064–CM001075, and the data on expressed sequences are available in the "Sequence Read Archive" under accession number SRA049915, GSE33507, SRA050797 and SRA048144.

    The Tomato Genome Consortium was responsible for the report, and reflects a vast amount of work by hundreds of researchers around the world.  Named as corresponding authors are:

    Shusei Sato, Satoshi Tabata, Lukas A. Mueller, Sanwen Huang, Yongchen Du, Chuanyou Li, Zhukuan Cheng, Jianru Zuo, Bin Han, Ying Wang, Hongqing Ling, Yongbiao Xue, Doreen Ware, W. Richard McCombie, Zachary B. Lippman, Stephen M. Stack, Steven D. Tanksley, Yves Van de Peer, Klaus Mayer, Gerard J. Bishop, Sarah Butcher, Nagendra Kumar Singh, Thomas Schiex, Mondher Bouzayen, Antonio Granell, Fernando Carrari, Gianluca De Bellis, Giovanni Giuliano, Glenn Bryan, Michiel J. T. van Eijk, Hiroyuki Fukuoka, Debasis Chattopadhyay, Roeland C. H. J. van Ham, Doil Choi, Jane Rogers, Zhangjun Fei, James J. Giovannoni, Rod Wing, Heiko Schoof, Blake C. Meyers, Jitendra P. Khurana, Akhilesh K. Tyagi, Tamas Dalmay, Andrew H. Paterson, Xiyin Wang, Luigi Frusciante, Graham B. Seymour, Bruce A. Roe, Giorgio Valle, Hans H. de Jong and René M. Klein Lankhorst

    Note: the complete list can be found in the Supplementary Information (Supplementary Information).

    The Tomato Genome Consortium includes scientists from The Kazusa DNA Research Institute, Japan; 454 Life Sciences Co. (Roche), USA; Amplicon Express Inc., USA; Beijing Vegetable Research Center, China; National Center for Gene Research, Chinese Academy of Sciences, Shanghai, China; BGI-Shenzhen, China; BMR-Genomics SrL, Italy; Boyce Thompson Institute for Plant Research, Cornell University, USA; Centre for Biosystems Genomics, The Netherlands; Centro Nacional de Analisis Genomico, Barcelona, Spain; China Agricultural University, Beijing, China; Institute of Vegetables and Flowers Chinese Academy of Agricultural Sciences, Beijing, China; Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China; Wuhan Botanical Garden, Chinese Academy of Sciences, Beijing, China; Cold Spring Harbor Laboratory, USA; Colorado State University, USA; National Taiwan University, Taipei; Department of Plant Biology, Cornell University, USA;  Centre for Genomic Regulation, University Pompeu Fabra, Barcelona, Spain; Department of Plant Biotechnology and Bioinformatics, Ghent University, Belgium; Faculty of Agriculture, The Hebrew University of Jerusalem, Israel; Institute of Industrial Crops, Heilongjiang Academy of Agricultural Sciences, China; Institute for Bioinformatics and Systems Biology (MIPS), Helmholtz Center for Health and Environment, Germany; College of Horticulture, Henan Agricultural University, China; Department of Life Sciences, Imperial College London, UK; NRC on Plant Biotechnology, Indian Agricultural Research Institute, India; INRA, Génétique et amélioration des fruits et légumes, France; INRA, Biologie du Fruit et Pathologie, France; Unité de Biométrie et d'Intelligence Artificielle, INRA, France; INRA-CNRGV, France; Plateforme bioinformatique Genotoul, Biométrie et Intelligence Artificielle, INRA, France; Institut National Polytechnique de Toulouse – ENSAT, Université de Toulouse, France; Instituto de Biología Molecular y Celular de Plantas (CSIC-UPV), Spain; Instituto de Hortofruticultura Subtropical y Mediterránea "La Mayora", Universidad de Malaga – Consejo Superior de Investigaciones Cientificas (IHSM-UMA-CSIC), Spain; Instituto de Biotecnología, Argentina; Institute for Biomedical Technologies, National Research Council of Italy; Institute of Plant Genetics, Research Division Portici, National Research Council of Italy; ENEA, Casaccia Research Center, Italy; Scuola Superiore Sant'Anna, Italy; ENEA, Trisaia Research Center, Italy; James Hutton Institute, UK; Barcelona Supercomputing Center, Spain; Institute of Research in Biomedicine, Barcelona, Spain; ICREA, Barcelona, Spain; Keygene N.V., Wageningen, The Netherlands; Plant Systems Engineering Research Center, Korea Research Institute of Bioscience and Biotechnology, Republic of Korea; Life Technologies, USA; Life Technologies, France; Max Planck Institute for Plant Breeding Research, Germany; School of Agriculture, Meiji University, Japan; Department of Plant Science and Plant Pathology, Montana State University, USA; NARO Institute of Vegetable and Tea Science, Japan; National Institute of Plant Genome Research, India; Plant Research International, Business Unit Bioscience, Wageningen, The Netherlands; Institute of Plant Genetic Engineering, Qingdao Agricultural University, China; Roche Applied Science, Germany; Seoul National University, Department of Plant Science and Plant Genomics and Breeding Institute, Republic of Korea; Seoul National University, Department of Agricultural Biotechnology, Republic of Korea; Seoul National University, Crop Functional Genomics Center, Republic of Korea; High-Tech Research Center, Shandong Academy of Agricultural Sciences, China; Institute of Vegetables, Shandong Academy of Agricultural Sciences, China; School of Life Sciences, Sichuan University, China; Sistemas Genomicos, Spain; College of Horticulture, South China Agricultural University, China; Syngenta Biotechnology, Inc., USA; Norwich Research Park, UK; Department of Botany, The Natural History Museum, UK; United States Department of Agriculture – Agricultural Research Service, Robert W. Holley Center, USA; Instituto de Hortofruticultura Subtropical y Mediterranea, Departamento de Biologia Molecular y Bioquimica, Spain; Centre de Regulacio Genomica, Universitat Pompeu Fabra, Spain; Arizona Genomics Institute, USA.; Crop Bioinformatics, Institute of Crop Science and Resource Conservation, University of Bonn, Germany;  Department of Plant and Soil Sciences, and Delaware Biotechnology Institute, University of Delaware, USA; Interdisciplinary Centre for Plant Genomics and Department of Plant Molecular Biology, University of Delhi South Campus, India.; University of East Anglia, UK; Department of Biology and the UF Genetics Institute, USA; Plant Genome Mapping Laboratory, University of Georgia, USA; Center for Genomics and Computational Biology, School of Life Sciences, and School of Sciences, Hebei United University, China; J. Craig Venter Institute, USA; University of Naples "Federico II" Department of Soil, Plant, Environmental and Animal Production Sciences, Italy; Division of Plant and Crop Sciences, University of Nottingham, UK; Department of Chemistry and Biochemistry, University of Oklahoma, USA; CRIBI, University of Padua, Italy; Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, USA.; Department of Agriculture and Environmental Sciences, University of Udine, Italy; Wageningen University, Laboratory of Genetics, Wageningen, The Netherlands; Wageningen University, Laboratory of Plant Breeding, Wageningen, The Netherlands; Wellcome Trust Sanger Institute Hinxton, UK; Ylichron SrL, Casaccia Research Center, Italy; and Plant Engineering Research Institute, Sejong University, Republic of Korea.

  • BIO International Convention 2012 Preview

    BIO and the Prometheus Supreme Court Case

    By Andrew Williams —

    BIO International ConventionThe 2012 BIO International Convention in Boston is less than two weeks away.  If you are planning on attending, you probably already know that the amount of information and opportunities available at BIO can be daunting.  Therefore, over the next two weeks, Patent Docs will be highlighting a few sessions or other opportunities, in thematic fashion, to help you navigate your way through the convention.  For example, today we present opportunities for those attendees who have been thinking about how Prometheus is going to affect their research or practice (and we are not talking about Ridley Scott's highly anticipated new movie — opening this Friday at a theater near you).  Of course, Patent Docs authors and contributors will be present at BIO as part of the MBHB contingent, and Patent Docs readers are encouraged to stop by the MBHB booth to discuss Prometheus (or whatever other topic is of interest to you) (#1335 – Hall A).

    Last year, just prior to the 2011 BIO International Convention in Washington D.C., the Supreme Court granted certiorari in the Mayo Collaborative Services v. Prometheus Laboratories Inc. case.  As Patent Docs readers are well aware, the claims at issue in that case involved optimizing drug dosage in the treatment of autoimmune diseases by determining the level of a metabolite in a patient.  In the intervening year, the Supreme Court reversed the Federal Circuit's determination that the diagnostic claims were patent eligible, and instead held that they were unpatentable laws of nature, with any additional steps found in the claims to involve "well-understood, routine, conventional activit[ies] previously engaged in by researchers in the field."  And, even though the opinion warned that patent eligibility should not depend on the "draftsman's art," there has already been plenty of discussion of how far-reaching Prometheus will be, and what a patent practitioner can do to ensure that any new or current claims will not suffer the same fate.  BIO looks like it will be no exception to this trend.  And, even though we are confident that there will be plenty of discussion throughout the convention, we are highlighting three break-out sessions that promise to address this case, and the issues it presents.

    First, the Personalized Medicine and Diagnostics Track will present "IP Challenges for Personalized Medicine & Diagnostics," on Monday, June 18 at 2:00 to 3:30 pm.  The session promises to look at how the ability to obtain patents to personalized medicine will be affected by the recent court cases of Myriad, Classen, and Prometheus, as well as the emotionally charged public perception of such patents.  The panel will explore the tension between such public perceptions and the demonstrable benefits to patients of such "companion diagnostics" patents by highlighting the intersection of personalized medicine & intellectual property protection.  Of course, just how companies can deliver on the promise of personalized medicine in this environment remains a question.  This panel includes the Associate General Counsel of BIO, Hans Sauer; as well as Annabelle Bennett, Federal Court of Australia Judge; and Thomas Triolo, Senior Counsel at Merck & Co., Inc.  The session will be moderated by Jennifer Gordon of Baker Botts L.L.P.

    Not to be outdone, the Biotech Patenting and Tech Transfer Track will be presenting "IP issues Affecting Biomarker-Based Diagnostics and Personalized Medicine" on Wednesday, June 20, at 3:00-3:30 pm.  This session includes a panel of international attorneys that will discuss the impact of recent court cases, legislation, and scientific issues on patent procurement and protection in the field of biomarkers and personalized medicine.  The panel promises to focus on inventions relating to the use of genetic and non-genetic human variation to predict susceptibility to disease and/or identify patients that will benefit from personalized treatments.  In addition to the impact of the America Invents Act and court decisions such as Myriad and Prometheus, the panel will discuss scientific issues are impacting patent procurement (such as what types of data are or can be required), and cross-border and joint infringement considerations that impact the ability to enforce such patents.  The panel includes:  Thorlakur Jonsson, Director of Intellectual Property of deCODE genetics ehf; Simon O'Brien, Chartered Patent Attorney with D. Young & Co.; John Tessensohn, Board Member of Shusaku Yamamoto Patent Attorneys; and David Gass of Marshall, Gerstein & Borun, LLP.  This session will be moderated by Jan Skouv, Director IPR of Exiqon A/S.

    Last, but certainly not least, the Biotech Patenting and Tech Transfer Track is also presenting "Recent Developments in Patentability: Prometheus, Myriad, Classen, and the Patentability of Diagnostic Claims," on Tuesday, June 19, at 8:30-9:45 am.  This session promises to provide insights on these major court cases and the decision-making behind them.  The panel of patent-law experts and practitioners will provide insights into cutting edge legal issues regarding diagnostic methods, will consider an insider's view of decision-making at the Supreme Court and Federal Circuit, and will identify the consequences of these cases for biotech companies.  The panel includes: Kevin Marks, Vice President and General Counsel of Roche Molecular Diagnostics; John Whealan, Associate Dean for Intellectual Property at The George Washington University Law School; Neal Katyal of Hogan Lovells; and Seth Waxman of WilmerHale.  This session will be moderated by Mark Fleming of WilmerHale.

  • USPTO Issues Proposed Rules for Implementing Micro Entity Status

    By Donald Zuhn —

    USPTO SealLast week, the U.S. Patent and Trademark Office announced proposed amendments to the rules of practice to implement the micro entity provision of § 10 of the Leahy-Smith America Invents Act.  Pursuant to that section of the AIA, the fees for filing, searching, examining, issuing, appealing, and maintaining patent applications and patents shall be reduced by 75% for any micro entity as defined in new 35 U.S.C. § 123.  New § 123 defines micro entities as follows:

    § 123. Micro entity defined
        (a) IN GENERAL.-For purposes of this title, the term 'micro entity' means an applicant who makes a certification that the applicant-
            (1) qualifies as a small entity, as defined in regulations issued by the Director;
            (2) has not been named as an inventor on more than 4 previously filed patent applications, other than applications filed in another country, provisional applications under section 111(b), or international applications filed under the treaty defined in section 351(a) for which the basic national fee under section 41(a) was not paid;
            (3) did not, in the calendar year preceding the calendar year in which the applicable fee is being paid, have a gross income, as defined in section 61(a) of the Internal Revenue Code of 1986, exceeding 3 times the median household income for that preceding calendar year, as most recently reported by the Bureau of the Census; and
            (4) has not assigned, granted, or conveyed, and is not under an obligation by contract or law to assign, grant, or convey, a license or other ownership interest in the application concerned to an entity that, in the calendar year preceding the calendar year in which the applicable fee is being paid, had a gross income, as defined in section 61(a) of the Internal Revenue Code of 1986, exceeding 3 times the median household income for that preceding calendar year, as most recently reported by the Bureau of the Census.

    The Office has published the proposed changes to the rules implementing micro entity status in a Federal Register notice (77 Fed. Reg. 31806).  The proposed changes specify procedures for claiming micro entity status, paying fees as a micro entity, notifying the Office regarding the loss of micro entity status, and correcting payments erroneously made using the reduced micro entity rate.

    Among the rules changes being proposed is a new provision setting out the requirements to qualify as a micro entity (which tracks § 123 above) and procedures relating to micro entity status that track 37 C.F.R. § 1.27 (which provides a definition of small entities and procedures for establishing status as a small entity to permit payment of small entity fees; specifies when a determination of entitlement to small entity status and notification of loss of entitlement to small entity status are required; describes fraud on the Office as it pertains to claiming small entity status).  To claim micro entity status, applicants will have to make a certification of entitlement to that status (preferably using a form the Office is currently developing).  Applicants will only have to claim micro entity status once during the prosecution of an application, but will be permitted to pay the reduced micro entity fee amount only if the applicant is entitled to micro entity status on the date a fee is paid.  Because 35 U.S.C. § 123 requires a certification of micro entity status, the proposed rules regarding micro entity status will not permit applicants to establish micro entity status by merely paying the micro entity fee (as applicants may do to establish small entity status) or secure a refund by subsequently establishing micro entity status (as permitted for small entities).

    While noting that "[t]he micro entity provisions of 35 U.S.C. 123 are currently in effect," the Office acknowledges in the notice that "no patent fee is currently eligible for the seventy-five percent micro entity reduction as no patent fee has yet been set or adjusted under section 10 of the Leahy-Smith America Invents Act."  The Office indicated that fees for micro entities would be forthcoming in a separate rulemaking.  The notice contains a discussion of the specific rules changes and the full text of new § 1.29 (Micro entity status), which would be added to 37 C.F.R. Part I.

    Comments regarding the proposed changes can be sent by e-mail to micro_entity@uspto.gov; by regular mail to:  Mail Stop Comments — Patents, Commissioner for Patents, P.O. Box 1450, Alexandria, VA 22313–1450, marked to the attention of James Engel, Senior Legal Advisor, Office of Patent Legal Administration, Office of the Deputy Commissioner for Patent Examination Policy; or via the Federal eRulemaking Portal.  Comments must be submitted by July 30, 2012.

  • Court Report – Part II

    By Sherri Oslick —

    Gavel In an effort to catch up with recently filed biotech and pharma cases, Patent Docs presents this additional installment of Court Report. 

    Exelixis, Inc. v. Honorable David J. Kappos
    1:12-cv-00574; filed May 29, 2012 in the Eastern District of Virginia

    Review and correction of the patent term adjustment calculation made by the U.S. Patent and Trademark Office for U.S. Patent No. 8,067,436 ("c-Met Modulators and Methods of Use," issued November 29, 2011).  View the complaint here.


    Shire Development, LLC et al. v. Mylan Pharmaceuticals, Inc. et al.
    8:12-cv-01190; filed May 25, 2012 in the Middle District of Florida

    • Plaintiffs:  Shire Development, LLC; Shire Pharmaceutical Development, Inc.; Cosmo Technologies Ltd.; Giuliani International Ltd.
    • Defendants:  Mylan Pharmaceuticals, Inc.; Mylan, Inc.

    Infringement of U.S. Patent No. 6,773,720 ("Mesalazine Controlled Release Oral Pharmaceutical Compositions," issued August 10, 2004) following a Paragraph IV certification as part of Mylan's filing of an ANDA to manufacture a generic version of Shire's Lialda® (mesalamine, used to induce remission in patients with active, mild to moderate ulcerative colitis).  View the complaint here.


    Pfizer Inc. et al. v. Sandoz Inc.
    1:12-cv-00654; filed May 24, 2012 in the District Court of Delaware

    • Plaintiffs:  Pfizer Inc.; Wyeth LLC; Wyeth Pharmaceuticals Inc.
    • Defendant:  Sandoz Inc.

    Infringement of U.S. Patent No. 8,026,276 ("Parenteral CCI-779 Formulations Containing Cosolvents, an Antioxidant, and a Surfactant," issued September 27, 2011) following a Paragraph IV certification as part of Sandoz's filing of an ANDA to manufacture a generic version of Pfizer's Torisel® (temsirolimus injection, used to treat advanced renal cell carcinoma).  View the complaint here.