Patent Law Weblog

recent posts

about

  • Webcast on Patent Prosecution

    Strafford #1Strafford will be offering a webcast on "Patent Prosecution: FTO Opinions, Examiner Interactions, Patent Drafting and More" on September 26, 2017 from 8:30 to 5:20 pm (PDT).  This one-day seminar will provide the tools needed to prosecute patents efficiently and effectively — from clearing the patent, to interacting with examiners, to overcoming rejections, and successfully withstanding PTAB and court scrutiny.  The webcast will include sessions on the following topics:

    • Freedom-to-Operate Opinions
    • USPTO Examiner Count System and Examiner Interview Strategies
    • Reflections on PTAB and Where is Patent Law Heading
    • Overcoming 101 Rejections
    • Drafting Patent Applications to Withstand PTAB Scrutiny
    • Conflicts in Patent Prosecution [Ethics]

    The registration fee for the webcast is $1,497.  Those interested in registering for the webinar, can do so here.

  • IPO Webinar Provides ITC Update

    IPO #2The Intellectual Property Owners Association (IPO) will offer a one-hour webinar entitled "ITC Update: Brushing Off the PTAB and Other Recent Developments" on September 27, 2017 from 2:00 to 3:00 pm (ET). G. Brian Busey of Morrison & Foerster LLP, Blaney Harper of Jones Day, and Lauren Hoffer of Dell Technologies will examine the latest on a number of important issues relating to ITC practice, discussing such topics as:

    • Brushing off the PTAB
    • The latest on "domestic industry"
    • Expensive hassles for third parties
    • The 100-day Pilot Program

    The registration fee for the webinar is $135 (government and academic rates are available upon request).  Those interested in registering for the webinar can do so here.

  • Webinar on Patentability to Software Inventions

    LexisNexisLexisNexis will be offering a webinar/teleconference entitled "'Alice' Before 'Alice' " on September 21, 2017 at 2:00 pm (ET).  Chris Holt, Vice President of Patent Analytics, LexisNexis PatentAdvisor®, and Megan McLoughlin, Product Director for PatentAdvisor™ will will discuss the following:

    • Before Alice, a large number of examiners were consistently refusing to give patentable weight to "non-functional descriptive material";
    • Many of these examiners are now the same examiners that refuse to allow software applications in view of patentable subject matter standards that have arisen since the Alice decision;
    • Some examiners are even now continuing to utilize the "non-functional descriptive material" rejection basis; and
    • The long standing and obvious connection between assignment of an application to an art unit and aggressive utilization of the non-patentable subject matter rejection.

    Those interested in registering for the webinar, can do so here.

  • Webinar on Safeguarding University IP When Structuring Deals in China

    Technology Transfer Tactics will be offering a webinar entitled "Best Practices for Safeguarding University IP When Structuring Deals in China" on September 26, 2017 from 1:00 to 2:30 pm (Eastern).  Dan Harris of Harris Bricken will how to protect your technology and other IP interests from being counterfeited, pirated, or otherwise misappropriated by Chinese companies.  The webinar will cover the following topics:

    • How to choose a good Chinese partner
    • Identifying your IP assets that need protection
    • How to structure and draft your China deal:
        – Licensing IP
        – Selling IP
        – Producing goods
    • How to structure your China technology and IP licensing deals with concern for:
        – Export issues
        – Ownership rights
    • Drafting China employee and third party contracts to protect your IP
    • IP registrations: What you should know about trademarks, patents, copyrights, and licensing agreements
    • Understanding the wants and needs of Chinese entities and universities and how to meet them
    • Cultural nuances

    The registration fee for the webinar is $197.  Those interested in registering for the webinar, can do so here.

    Technology Transfer Tactics

  • FDA Approves First Cancer-Treatment Biosimilar — Amgen’s Mvasi

    By Andrew Williams —

    FDAEarlier today, the U.S. Food and Drug Administration approved Amgen's application to market Mvasi (bevacizumab-awwb), a biosimilar to Genentech's Avastin therapeutic antibody for the treatment of multiple types of cancer.  This marks the first time that a biosimilar for the treatment of cancer has been approved by the FDA.  According to the FDA's press release, Mvasi was approved for the following indications in adult patients:

    • Metastatic colorectal cancer, in combination with intravenous 5-fluorouracil-based chemotherapy for first- or second-line treatment.  Mvasi is not indicated for the adjuvant treatment of surgically resected colorectal cancer.
    • Metastatic colorectal cancer, in combination with fluoropyrimidine-irinotecan- or fluoropyrmidine-oxaliplatin-based chemotherapy for the second-line treatment of patients who have progressed on a first-line bevacizumab product-containing regimen.  Mvasi is not indicated for the adjuvant treatment of surgically resected colorectal cancer.
    • Non-squamous non-small cell lung cancer, in combination with carboplatin and paclitaxel for first line treatment of unresectable, locally advanced, recurrent or metastatic disease.
    • Glioblastoma with progressive disease following prior therapy, based on improvement in objective response rate.  No data is available demonstrating improvement in disease-related symptoms or survival with bevacizumab products.
    • Metastatic renal cell carcinoma, in combination with interferon alfa.
    • Cervical cancer that is persistent, recurrent, or metastatic, in combination with paclitaxel and cisplatin or paclitaxel and topotecan.

    FDA Commissioner Scott Gottlieb, M.D., indicated that the FDA would "continue to work hard to ensure that biosimilar medications are brought to the market quickly, through a process that makes certain that these new medicines meet the FDA's rigorous gold standard for safety and effectiveness."  As apparent evidence of this commitment, Amgen's biosimilar application was filed last November, and accepted by the FDA for review on January 4, 2017 (according to a complaint filed by Genentech in Delaware last February).  This means that the FDA approved this aBLA in less than nine months from the acceptance of the application.

    AmgenInterestingly, there is currently no litigation pending that could prevent Amgen from launching its new biosimilar drug product.  Even though Amgen had disclosed its aBLA pursuant to the BPCIA, Genentech did file the aforementioned complaint to force Amgen to provide Genentech with manufacturing information allegedly not found in the aBLA.  Genentech had provided Amgen with a written request for information related to, among other things, the host cells used to manufacture the drug, the composition of the cell culture media, the extent and nature of the glycosylation patterns of the drug, the transformation of the culture cells, the sparging of the culture fluid, the Protein A chromatography purification process, any cation or anion exchange chromatography used to purify the drug, any viral inactivation steps, all formulations considered or used, and the filling of vials and/or the use of tangential flow filtration.  Amgen apparently took the position that it had satisfied its obligation under 42 U.S.C. § 262(l)(2)(A) by providing the aBLA.  The Court agreed that Genentech could not obtain relief, granting a 12(b)(1) motion filed by Amgen to dismiss the case for lack of subject matter jurisdiction in light of the Federal Circuit's holding in Amgen v. Sandoz.  No subsequent litigation has yet been filed, so it is unclear whether the Patent Dance has occurred notwithstanding the alleged disclosure deficiency.

    Mvasi is the seventh biosimilar application to be approved by the FDA, and the second in less than a month.  In late August, the FDA approved Boehringer Ingelheim's aBLA for Cyltezo (adalimumab-adbm), a biosimilar to Abbvie's Humira® (see "Boehringer Ingelheim Pharmaceuticals, Inc. receives FDA approval for CyltezoTM (adalimumab-adbm), a biosimilar to Humira®, for the treatment of multiple chronic inflammatory diseases").  This was the second approved biosimilar to this reference product, and the first biosimilar approval obtained by Boehringer Ingelheim.  Nevertheless, just as with Amgen's approved Humira® biosimilar, concurrent litigation will likely keep Cyltezo off the market for the foreseeable future.

    We will continue to monitor these situations and report any updates as warranted.

  • Allergan Avails Itself of Sovereign Immunity

    By Kevin E. Noonan –

    The 11th amendment to the Constitution reads:

    The judicial power of the United States shall not be construed to extend to any suit in law or equity, commenced or prosecuted against one of the United States by citizens of another state, or by citizens or subjects of any foreign state.

    AllerganThe application of this principle in patent cases has been controversial, both in litigation (see "The Wall Street Journal's Problem with the U.S. Constitution") and as a shield against inter partes review, by states and in particular state universities claiming the immunity as "arms of the state" (see Covidien LP v. University of Florida Research Foundation Inc. and Neochord, Inc. v. University of Maryland).  Nonetheless, immunity is well established as to the several States.  Last week, Allergan creatively availed itself of this immunity by assigning patents challenged in IPR proceedings to the St. Regis Mohawk Nation (SRMN), which also has the capacity to invoke the protection of sovereign immunity against suit.

    The Orange Book-listed patents, Nos. 8,629,111; 8,633,162; 8,642,556; 8,648,048; 8,685,930, and 9,248,191, protect Allergan's RESTASIS® (Cyclosporine Ophthalmic Emulsion 0.05%), used for chronic dry eye.  Allergan paid SRMN $13.75 million upon transferring these patents, which SRMN licensed to Allergan for $15 million per year until the patents expire on August 27, 2024.  The benefits to both Allergan and SRMN can be appreciated by the estimates of revenues for RESTASIS®:

    Chart
    (Chart obtained here.)

    Allergan is not alone in entering into such arrangements; in August SRC (Cray) Labs LLC transferred patent rights to the tribe, and "dozens and dozens of tribes" are pursuing such arrangements, according to David Pridham, chief executive of Dominion Harbor Group as quoted by Reuters (see "Tech entity has tribal patent deal similar to Allergan's").

    The concept of sovereign immunity stems from British common law, banning lawsuits against the king.  Although not explicitly stated in the Amendment, the Supreme Court has interpreted 11th Amendment immunity to extend to actions of a citizen against the state in which she resides.  Hans v. Louisiana, 134 U.S. 1 (1890).  The rationale behind the immunity conferred by the Amendment is that the "States entered the federal system with their sovereignty intact," Blatchford v. Native Village of Noatak, 501 U.S. 775 (1991), and that "the sovereign immunity of the States neither derives from nor is limited by the terms of the Eleventh Amendment.  Rather, . . . the States' immunity from suit is a fundamental aspect of the sovereignty which the States enjoyed before the ratification of the Constitution, and which they retain today," Alden v. Maine, 527 U.S. 706 (1999).  However, the immunity is not absolute.  It can be waived, and many states (as well as the federal government) have waived sovereign immunity in suits for tort and contract.  Certain U.S. Constitutional provisions trump the immunity, such as the Bankruptcy Clause and the 14th Amendment.  However, patent law does not fall within any federal law exemption, and the Supreme Court has decided expressly that States enjoy sovereign immunity against suits for patent infringement.  Florida Prepaid Postsecondary Education Expense Board v. College Savings Bank, 527 U.S. 627 (1999).

    The various tribes of Native Americans have also been held to enjoy sovereign immunity, albeit with certain limitations that do not apply to the States.  The immunity stems from common law rather than by statute or Act of Congress, Turner v. United States, 28 U.S. 354 (1919), and has been applied both to state action and private suit.  United States v. United States Fidelity & Guaranty Co., 309 U.S. 506 (1940); Puyallup Tribe, Inc. v. Department of Game of State of Washington, 433 U.S. 165 (1977); and Kiowa Tribe of Oklahoma v. Mfg. Technologies, Inc., 523 U.S. 751, 755 (1998).

    Congress has the power to abrogate tribal sovereign immunity, under the Supreme Court's decision in United States v. Lara, 541 U.S. 193, 200 (2004), that "the Constitution grants Congress broad general powers to legislate in respect to Indian tribes, powers that we have consistently described as 'plenary and exclusive.'"  However, Congress can do so only if the intent is "clear and unambiguous" or "unequivocally expressed."  Santa Clara Pueblo v. Martinez, 436 U.S. 49 (1978); see also Michigan v. Bay Mills Indian Cmty., 134 S.Ct. 2024 (2014).

    For some this development, while on its face consistent with the law, rankles.  In earlier sovereign immunity cases the inventors (usually university personnel) were obligated (inter alia, under the Bayh-Dole Act) to assign their inventions to the university and state universities were readily recognized as arms of the state for whom the immunity applied.  Here, Allergan is unabashedly obtaining the benefit of tribal sovereign immunity in a commercial transaction.  While such a transfer is well within Allergan's rights to alienate these patents as a private property right, avoidance of IPR as not only a consequence but the express intent of the transfer distinguishes this use of sovereign immunity from other instances.  (And of course it remains to be seen whether patents are exclusively a private property right or more in the nature of a government grant, see Oil States Energy Services, LLC v. Greene's Energy Group, LLC).

    Recent history suggests that, at a minimum, Congress will want to hear from the parties on this arrangement.  But in light of earlier controversies like Mylan's Epi-Pen cost increase and the Martin Shkreli affair at a Turing Pharmaceuticals, as well as more general concerns about patent quality and validity and increasing drug costs, it is likely that there will be some effort in Congress to prevent maneuvers such as this one.  The courts have made it clear that any limitation on SRMN's sovereign immunity is solely within the "plenary power" of Congress.  But passage of such a measure must remain in doubt in the current political climate, given the inability of Congress to pass legislation its members seem to be much more committed to than such an esoteric question as sovereign immunity, no matter how relevant the issue may be to their constituents' access to affordable drugs.

    Allergan issued a press release on the transfer.

  • General Plastic Industrial Co. v. Canon Kabushiki Kaisha (PTAB 2017)

    By James Korenchan —

    USPTO SealIn a decision entered last week, the Patent Trial and Appeal Board (PTAB) of the U.S. Patent and Trademark Office made clear its intention going forward to weigh seven factors in determining whether to deny follow-on inter partes review (IPR) petitions.

    On September 6, 2017, the Board entered a decision denying Petitioner General Plastic Industrial Co., Ltd.'s requests for rehearing five related IPR proceedings.  General Plastic first filed a set of IPR petitions challenging two of Canon Kabushiki Kaisha's patents, after which the Board denied institution on the merits.  Nine months later, they filed five follow-on petitions challenging the same patents.  The Board did not institute any of the follow-on petitions.

    As a general matter, a petitioner's burden of proof for institution of an IPR is set forth in 35 U.S.C. § 314(a):

    The Director may not authorize an inter partes review to be instituted unless the Director determines that the information presented in the petition filed under section 311 and any response filed under section 313 shows that there is a reasonable likelihood that the petitioner would prevail with respect to at least 1 of the claims challenged in the petition.

    In its rehearing requests, General Plastic argued that the Board erroneously relied on § 314(a), asserting that the application of § 314(a) to follow-on petitions "conflicts with the express wording" of 35 U.S.C. § 325(d), under which the Board is granted the discretion to deny institution when "the same or substantially the same prior art or arguments previously were presented to the Office."  General Plastic further argued that the Board's rationale in denying its follow-on petitions created, in essence, a rule that petitioners could not use follow-on petitions to challenge the same patent more than once.

    In its decision denying the requests for rehearing, the Board noted that the express language of both § 314(a) and § 325(d) commits institution of review to the Director's — and thus, the Board's — discretion, and provides no requirement that, in certain scenarios, review must be instituted.  Along the same lines, the Board also noted that "[t]here is no per se rule precluding the filing of follow-on petitions after the Board's denial of one or more first-filed petitions on the same patent," and further acknowledged that "there may be circumstances where multiple petitions by the same petitioner against the same claims of a patent should be permitted, and that such a determination is dependent on the facts at issue in the case."  Specifically, the Board pointed to seven factors that it has consistently weighed in analyzing the facts of a case and determining whether to exercise its discretion in denying follow-on petitions:

    1. whether the same petitioner previously filed a petition directed to the same claims of the same patent;

    2. whether at the time of filing of the first petition the petitioner knew of the prior art asserted in the second petition or should have known of it;

    3. whether at the time of filing of the second petition the petitioner already received the patent owner's preliminary response to the first petition or received the Board's decision on whether to institute review in the first petition;

    4. the length of time that elapsed between the time the petitioner learned of the prior art asserted in the second petition and the filing of the second petition;

    5. whether the petitioner provides adequate explanation for the time elapsed between the filings of multiple petitions directed to the same claims of the same patent;

    6. the finite resources of the Board; and

    7. the requirement under 35 U.S.C. § 316(a)(11) to issue a final determination not later than 1 year after the date on which the Director notices institution of review.

    The Board highlighted the goals of some of these factors, noting that it formulated the factors "to take undue inequities and prejudices to [the] Patent Owner into account."  Factors 2, 4, and 5, for instance, allow the Board to "assess and weigh whether a petitioner should have or could have raised the new challenges earlier."  And factor 3 allows the Board to assess the potential benefit on the petitioner "from receiving and having the opportunity to study [the] Patent Owner's Preliminary Response, as well as [the Board's] institution decisions on the first-filed petitions, prior to [the petitioner's] filing of follow-on petitions."

    Applying all seven factors, the Board had determined that all but factor 7 weighed strongly against instituting General Plastic's follow-on petitions.  For instance, with respect to factor 1, both General Plastic's first petitions and its follow-on petitions challenged the same claims of the same patent.  With respect to factor 6, the Board found that its resources would be "more fairly expended on initial petitions, rather than follow-on petitions."  Further, with respect to factor 3, at the time General Plastic filed the follow-on petitions, they had already received Canon's preliminary response, the Board had already issued its decisions denying institution of the first petitions, and the Board had issued its decisions denying rehearing of those decisions.  And with respect to both factors 2 and 3, the Board considered the nine-month span between the first petitions and the follow-on petitions, noting that General Plastic "provided no meaningful explanation for the delay."

    With respect to factors 4 and 5, the Board drew particular attention to the timing of General Plastic's new prior art search, as well as to the "shifts in the prior art asserted and the related arguments in [its] follow-on petitions."  General Plastic had previously stated that they performed "two later searches" that turned up new prior art, which then led to the follow-on petitions.  However, these new prior art searches had not occurred until after the Board had denied institution of the first petitions.  According to the Board, General Plastic's actions in filing multiple petitions against the same claims, but with different arguments brought upon by new prior art, imposed the exact sort of inequities on Canon that the factors were formulated to address in the first place:

    Petitioner demonstrated that it found new prior art, but provided no explanation why it could not have found this new prior art earlier—prior to filing the first-filed petitions—through the exercise of reasonable diligence.  We additionally found that Petitioner had modified its challenges in the follow-on petitions in an attempt to cure the deficiencies that the Board identified in its first-filed petitions.  More specifically, the newly-asserted prior art . . . was a shift in Petitioner's positions and arguments from the first-filed petitions based on the analysis articulated in our Decisions Denying Institution of those petitions.  Moreover, the shift in Petitioner's challenges was not the consequence of a position that Patent Owner surprisingly advanced or the Board surprisingly adopted.

    Regarding the "should have known" standard for prior art in factor 2, the Board rejected General Plastic's argument that the Board's interpretation of this standard "would be self-defining to be adverse to Petitioners in every instance."  The Board then emphasized the importance of how any prior art references relied on in follow-on petitions must have been able to have been found with reasonable diligence.  While the Board seems willing to accept meaningful explanations as to why new prior art was not found at or before the time of filing a first petition, it noted that "[h]ere, the record is devoid of any explanation why Petitioner could not have found the newly asserted prior art in any earlier search(es) through the exercise of reasonable diligence."  Lastly, the Board rejected General Plastic's argument that the Board did not give enough weight to factor 7.

    In recent years, the Board has ranged from weighing only five of these seven factors to weighing all seven.  For example, the Board weighed only factors 1 through 5 when denying a follow-on petition in Xactware Solutions, Inc. v. Eagle View Tech., Inc., IPR2017-00034, Paper 9 (PTAB April 13, 2017).  Whereas, the Board weighed all seven in NVIDIA Corp. v. Samsung Elec. Co. IPR2016-00134, Paper 9 (PTAB May 4, 2016).  Furthermore, while the NVIDIA decision appeared to indicate that these were seven factors that the Board could optionally consider, this new ruling against General Plastic notably emphasized that the Board plans to consider all seven factors in the future:

    We recognize, also, that additional factors may arise in other cases for consideration, where appropriate.  However, the [seven] factors . . . , at the very least, serve to act as a baseline of factors to be considered in our future evaluation of follow-on petitions.

    With this plan being set, it will be interesting to see how the Board applies the factors in future cases, and to see whether new circumstances in such cases might bring about additional factors.

    Before Chief Administrative Patent Judge David P. Ruschke, Deputy Chief Administrative Patent Judge Scott R. Boalick, and Administrative Patent Judges Jameson Lee, Michael R. Zecher, Thomas L. Giannetti, Jennifer S. Bisk, And Sheila F. McShane
    Decision Denying Petitioner's Requests for Rehearing by Administrative Patent Judge Mcshane

  • The Domestication History of Apples Revealed by Genomic Analysis

    By Kevin E. Noonan –

    A major conceit of the "genomics" revolution, involving the various species-specific genome projects epitomized by the one for Homo sapiens was the idea that decoding a genome would tell us everything there was to know about the species.  In the first blush of acquiring this detailed sequence-based knowledge was forgotten what Stephen Jay Gould termed the "contingent" nature of natural history (although that view of life has recently been challenged due to more recent genomic research; see Losos, Improbable Destinies: Fate, Chance, and the Future of Evolution, Riverhead Books: August 8, 2017).  In Gould's view it was the "history" portion that was preeminent, because for any species its very existence was exquisitely determined by its genetic and evolutionary path.

    Last month, a cohort of China- and America-based researchers* published a paper illuminating the effect of human crop domestication on apples, entitled "Genome re-sequencing reveals the history of apple and supports a two-stage model for fruit enlargement," Nature Communications (at doi:10.1038/s41467-017-00336-7).  These scientists sequenced 117 cultivars of the domestic apple, Malus domestica Borkh.  Their data support the hypothesis that domesticated apples arose from Malus sieversii in the Tian Shan Mountains bordering China and Kazakhstan with "intensive introgressions" from M. sylvestris over the past 4,000-10,000 years.  (Interestingly, Malus sieversii from nearby Xinjiang China appears not to have contributed to apple domestication.)  From these origins, the apple dispersed to Western Europe along the Silk Road with additional introgressions with wild crab apples from Siberia (M. baccata (L.) Borkh.), the Caucasus (M. orientalis Uglitz.) and Europe (M. sylvestris Mill.).

    Silk Road
    Today, there are thousands of apple cultivars that are famously diverse in fruit size, sweetness, acidity, and skin color; the authors attribute large fruit size to inheritance from M. sieversii and firm texture and appetizing flavor coming from M. sylvestris.

    Apples differ from other domesticated fruits and grain, being reproductively self-incompatible and typically being propagated by grafting to heterologous rootstock.  Native apple trees grow disadvantageously tall (~40 meters) for example.  The researchers undertook their study to better elucidate the effects of human domestication on the apple at least in part due to these differences from other domesticated fruit species.

    These authors sequenced genomic DNA from 117 cultivars from 24 species ("35 M. domestica (24 scion and 11 rootstock cultivars), 10 M. sylvestris, 29 M. sieversii, 9 M. robusta, 6 M. baccata, 4 M. asiatica, 4 M. hupehensis, and 20 in the remaining 17 wild species with one or two accessions per species"); for context, there are more than 7,500 apple cultivars known.  Genomic sequence information (1060 Gb) was produced (average 9.06 Gb/cultivar accession, about a 12-fold sequence of the apple genome).  Prior work had identified ~57,000 genes in the apple genome; humans have about 30,000).  From these the researchers discerned 7,218,060 single nucleotide polymorphisms (SNPs), useful as genetic markers between the cultivar genomes; 431,597 indels (insertions or deletions) were also identified.  Comparison to the pear genome showed North American-derived apple species (M. ioensis, M. angustifolia, M. fusca, and M. coronaria) were most closely related to pear, while M. domestica and M. sylvestris formed a distinct subclade within the clade further comprising M. sieversii; the paper reports that the introgression of M. sylvestris into M. domestica was so intense that M. domestica DNA has closer similarity to M. sylvestris than to the progenitor M. sierversii species.

    Genetic evidence of domestication was exhibited by an analysis of genome-wide nucleotide diversity, which was lower in M. domestica than in M. sieversii, M. sylvestris or other wild species (but higher than peach).  The genomic evidence was also consistent with a weak domestication bottleneck.  An estimated 46% of the M. domestica genome was derived from M. sieversii, with another 21% inherited from M. sylvestris; the origin of the remaining third of the apple genome was reported to be "uncertain."  At the gene level, 840 genes were characterized as having been selected for during initial domestication and 1,089 additional genes selected during introgression; ~29% (246) and ~31% (336) of these two sets of genes showed differential expression during apple fruit development.  Regions of "selective sweeps" (where linkage disequilibrium is suppressed, indicating section for genes involved in related phenotypes) were detected for genes associated with "fruit sugar content, firmness, color, hormone, and secondary metabolism" for the first set of such genes, while genes associated with fruit acidity were associated with the second (introgression) set of genes.  Specific genes so identified included six sugar transporters, genes for several important enzymes in the glycolysis/ gluconeogenesis pathway, and several sucrose and cellulose synthases, in addition to two aluminum-activated malate transporters, a malate dehydrogenase, a citrate synthase (from introgression genes) and a pyruvate decarboxylase in both sets.  These findings are consistent, according to the authors, with " the constant selection of sweet and firm fruits in the history of apple domestication" and "different selective forces for improving different agronomic traits from the two wild contributors during domestication."  Also significant but not subject to extensive explication in this paper were patterns of highly divergent SNPs in M. domestica and other wild species (which the paper states "provided ample information for broadening our understanding of apple speciation, differentiation, and evolution.")

    The authors identify fruit size as an important aspect of domestication for food crops generally, and report that two quantitative trait loci (QTL) genes (fw1 on chromosome 15 comprising 11 genes in sweeps from M. sierversii and 8 genes in sweeps from M. sylvestris, and fw2 on chromosome 8, comprising 7 genes in sweeps from M. sierversii and 21 genes in sweeps from M. sylvestris) were found to co-localized in the selective sweep loci.  Specific examples of such genes were genes for two β-galactosidase genes and a cell division regulatory gene, these genes showing expression patterns consistent with "their potential contribution to the increase of fruit size during apple domestication."

    The authors synthesize these experimental results to provide a "two-step" model for evolution of the apple with regard to fruit size.  First, and in contrast to species such as corn and tomato, fruit size in ancestral M. sieversii was already relatively large and thus there was less need to apply selective pressure than in other crops.  Accordingly, for apples "a weak selection in a highly heterozygous perennial crop" was able to yield large fruit.  Over thousands of years of domestication, they write, the relatively small increase in fruit size, as well as association of genetic markers for fruit weight, implies that it may be possible to use this knowledge for more selective breeding of larger apples in future.

    Another aspect of apple phenotype is firm fruit flesh texture, which imparts a crispy taste, increases shelf life, reduces bruising post-harvest and improves resistance to diseases.  It has been determined that fruit firmness is "directly linked to enzyme-mediated cell wall modification," citing Brummell, "Cell wall disassembly in ripening fruit," Funct. Plant Biol. 33, 103–19 (2006).  Using the selective sweep method, the authors report finding a region of chromosome 16 which both was the subject of "intensive human selection" and encoded cell wall-modifying enzymes, including three polygalacturonases and one glucan endo-1,3-beta-glucosidase.  Additional regions were found on chromosome 17 (having one sweep region encoding three cellulose synthase gene and another encoding a pectate lyase, a glucan endo-1,3-beta-glucosidase and an aldose 1-epimerase.  A sweep region on chromosome 12 was found to encode one endo-beta-1,4-mannase and two pectinesterase genes.  In many cases the authors reported that these genes were found to be differentially expressed during apple fruit development.

    Finally, the article reports on genetic evidence for selection for flavor; for apples, this represents a balance between sweetness and tartness (i.e., acidity).  Both traits had undergone human selective pressure during domestication.  For example, a region on chromosome 12 was identified that co-localized with a quantitative trait locus for sorbitol; genes at this locus included four sorbitol transporters and two sugar transporters, with the sorbitol transporter genes showing differential expression during apple fruit development.  Similar evidence was found for genes encoding enzymes involved in sugar metabolism and located on chromosome 13.  With regard to acidity, the paper reports that there is a region ~1.5kb upstream from an aluminum-activated malate transporter at a quantitative trait locus for tart taste.  This region was found to have "substantially reduced nucleotide diversity in M. domestica compared to M. sylvestris," as well as another region of reduced nucleotide diversity located ~750bp downstream from the coding sequence of this gene in M. siervesii.  M. sylvestris introgression also apparently contributed to reduced acidity in M. domestica related to "two other aluminum-activated malate transporter genes and a gene encoding malate dehydrogenase were identified in selection sweeps."

    * From State Key Laboratory of Crop Biology, Shandong Agricultural University; Shandong Centre of Crop Germplasm Resources, Shandong Academy of Agricultural Sciences; State Key Laboratory of Crop Stress Biology in Arid Areas, College of Horticulture, Northwest A&F University; The Institute of Pomology, Chinese Academy of Agricultural Sciences; College of Forestry and Horticulture, Research Centre of Specialty Fruits, Xinjiang Agricultural University; Mudanjiang Branch of Heilongjiang Academy of Agricultural Science; Key Laboratory of Biogeography and Bioresource in Arid Land, Xinjiang Institute of Ecology and Geography, Chinese Academy of Sciences, Peoples' Republic of China; Boyce Thompson Institute and Section of Horticulture, School of Integrative Plant Science, Cornell University; USDA-Agricultural Research Service, Plant Genetic Resources Unit and USDA-Agricultural Research Service, Robert W. Holley Center for Plant and Health.

  • Conference & CLE Calendar

    CalendarSeptember 12, 2017 – "Addressing and Understanding the Significant Developments and Latest Decisions on Patent Eligibility" (The Knowledge Group) – 3:00 to 5:00 pm (EST)

    September 12, 2017 – "How Can the Patents Ombudsman and Pro Se Assistance Programs Work For You?" (U.S. Patent and Trademark Office) – 12:00 to 1:00 pm (ET)

    September 12-13, 2017 – "Advanced Patent Prosecution Workshop 2017: Claim Drafting & Amendment Writing" (Practising Law Institute) – Chicago, IL

    September 13, 2017 – "Patent Litigation 2017 — The Courts and Patent Trial and Appeal Board" (Federal Circuit Bar Association) – 10:45 am to 3:10 pm (EDT), Wilmington, DE

    September 13-15 – FDA Boot Camp (American Conference Institute) – Boston, MA

    September 14, 2017 – "Patent Cooperation Treaty: Evaluating the Benefits and Risks, Obtaining International Patent Protection — Navigating the PCT, Priority, Selection of International Authorities, PCT Search and Examination, and More" (Strafford) – 1:00 to 2:30 pm (EDT)

    September 14, 2017 – "Private Right or Public Right? Preview of Oil States at the U.S. Supreme Court" (Intellectual Property Owners Association) – 2:00 to 3:00 pm (ET)

    September 14-15, 2017 – "International Patent Prosecution and Practice Seminar" (John Marshall Law School Center for Intellectual Property, Information & Privacy Law, World Intellectual Property Organization, and Kuhnen & Wacker) – Chicago, IL

    September 15, 2017 – "Patent Infringement: Significant Developments in 2017 and Beyond" (The Knowledge Group) – 3:00 to 5:00 pm (EST)

    September 19, 2017 – "The Continuing Influence of PTAB Proceedings on Bio/Pharma Litigation" (McDonnell Boehnen Hulbert & Berghoff LLP) – 10:00 am to 11:15 am (CT)

    September 19, 2017 – "Best Practices for Safeguarding University IP When Structuring Deals in China" (Technology Transfer Tactics) – 1:00 to 2:30 pm (Eastern)

    September 21-22, 2017 – Seminar on European Patent Law (Grünecker) – Munich, Germany

    September 22, 2017 – "Is Administrative Review of Granted Patents Constitutional?" (Center for Innovation Policy at Duke Law) – 1:00 pm to 4:00 pm (ET), Washington, DC

    September 26, 2017 – "USPTO on Restriction Practice, Terminal Disclaimers, and Patent Term Adjustment" (Intellectual Property Owners Association) – 2:00 to 3:00 pm (ET)

    October 2-3, 2017 – Paragraph IV Disputes master symposium*** (American Conference Institute) – Chicago, IL

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

  • IPO Webinar on Restriction Practice, Terminal Disclaimers, and Patent Term Adjustment

    IPO #2The Intellectual Property Owners Association (IPO) will offer a one-hour webinar entitled "USPTO on Restriction Practice, Terminal Disclaimers, and Patent Term Adjustment" on September 26, 2017 from 2:00 to 3:00 pm (ET).  Kathleen Fonda of the U.S. Patent and Trademark Office, Jeffrey Hohenshell of Medtronic, Inc, and Patent Docs author Kevin Noonan of McDonnell Hulbert Berghoff & Boehnen LLP will analyze the opportunities and pitfalls for patent prosecutors raised by restriction requirements, discussing such topics as:

    • After a restriction requirement, how can a patent applicant make sure that the subsequent application falls into the section 121 "safe harbor," while also garnering the longest protection through patent term adjustment?
    • What does it mean for claims in a new application to be "consonant" with those withdrawn from the earlier case?
    • The new amendment to the Manual of Patent Examining Procedure that describes when a terminal disclaimer can be withdrawn; and
    • Lessons learned from cases such as Hagenbuch v. Sonrai(E.D. Ill. 2016) on the potential danger of filing an ill-worded terminal disclaimer, and Janssen v. Celltrion(D. Mass. 2016) on serious consequences from filing a continuation instead of a divisional.

    The registration fee for the webinar is $135 (government and academic rates are available upon request).  Those interested in registering for the webinar can do so here.