•     By Kevin E. Noonan

    Cover
    An important consequence of the biotechnology revolution has been an increased understanding of the molecular biology of cancer.  Tyrosine kinases, including the eponymous src oncogene, provide important targets, comprising a family of plasma membrane proteins that in certain incarnations act as growth factor receptors.  Until now, therapeutic agents were primarily inhibitors of the tyrosine kinase activity, acting either directly or by preventing dimerization frequently associated with activating the kinase function.  However, a report published in Cancer Cell on May 6th illustrated a heretofore unknown activity of these receptors that calls into question the ultimate efficacy of the known inhibitors (see "Survival of Cancer Cells Is Maintained by EGFR Independent of Its Kinase Activity").

    The study was performed on the epidermal growth factor receptor, one of a family of such receptors that includes the HER2/neu target of Genentech’s breast cancer therapeutic Herceptin®.  EGFR (at left) is the target of several anticancer drugs, including several monoclonal antibodies.  These include panitumumab, sold by Amgen as Vectibix® for EGFR-expressing metastatic colorectal cancer, and cetuximab, sold by Bristol-Myers Squibb as Erbitux® for EGFR-expressing metastatic colorectal cancer and head and neck cancers.  Another class of anti-EGFR drugs inhibit the tyrosine kinase activity; these include gefitinib, sold by AstraZeneca as Iressa® for treating locally advanced or metastatic non-small cell lung cancer (NSCLC), and erlotinib, sold by Genentech as Tarceva® for the treatment of NSCLC and pancreatic cancer.  However, the success of these drugs has been more limited than expected, even in light of the otherwise poor prognosis of the typical patients for these therapies.

    The authors of the Cancer Cell report propose a reason for the less than expected results:  in addition to the known function of EGFR for promoting cellular proliferation associated with the tyrosine kinase activity, EGFR has the newly-found property of promoting active glucose uptake in cancer cells, preventing cell death.  The experiments were performed on human cancer cells in vitro, showing that treatment with EGFR inhibitors did not kill the cells (although it did prevent receptor autophosphorylation via the tyrosine kinase activity and reduce cell proliferation).  In contrast, transfecting the cells with EGFR-specific siRNA (that reduced EGFR expression) promoted autophagic cell death, i.e. cannibalization of cellular structures and components for energy.  Analysis of the cells for intracellular glucose revealed no change in the presence of EGFR inhibitors, but marked reductions after transfection of EGFR siRNA resulting in lowered or abolished EGFR expression.  Autophagy could be prevented by increasing the extracellular glucose concentration.

    The cancer cells assayed in these experiments expressed two cell surface glucose transporters:  GLUT1, which responds to increased extracellular glucose levels and is a passive transporter, and SGLT1, a sodium-dependent ATPase capable of active transport against a glucose concentration gradient.  Reduction of EGFR expression had no effect on GLUT1, but reduced SGLT1 detected by Western blot analysis.  The autophagic effect was mimicked by treating the cells with SGLT1-specific siRNA.  The combination of these results indicated that reduced intracellular glucose concentrations in response to reduced EGFR expression was mediated by SGLT1, and could be compensated by increased GLUT1-mediated glucose transport in response to increased extracellular glucose concentrations.  RT-PCR experiments on SGLT1 mRNA showed that SGLT1 gene expression was unaffected by EGFR downregulation, and treatment of proteosome inhibitors prevented reduction of cellular glucose levels mediated by SGLT1, establishing that SGLT1 degradation was the mechanism responsible for the observed effects.  Physical interaction between EGFR and SGLT1 was shown by co-immunoprecipitation using anti-EGFR antibodies, and this interaction was shown in MCF-7 cells (which express only very low levels of EGFR) transfected with wildtype as well as tyrosine kinase mutant EGFR.  The specificity of these effects was demonstrated by inhibiting endogenous EGFR expression using a 5′ untranslated region (UTR)-specific siRNA, and rescuing the phenotype by transfecting the cells with wildtype or tyrosine kinase mutant EGFR species lacking the 5′ UTR.  Finally, the specificity of SGLT1 involvement in autophagy caused by reduced intracellular glucose concentrations was established using MCF-7 cells (which do not express SGLT1) showing marked sensitivity to reductions in extracellular glucose in the culture media.

    These results provide an explanation for the persistence of cancer cells in the face of EGFR-targeted therapies, but also suggest a molecular explanation for the relative failure of these agents to be more effective as anticancer agents.  Importantly, these results also suggest that combination therapies, perhaps with anti-metabolic or antiglycolytic agents, may provide improvements in treatment for EGFR-expressing tumors.

  • Calendar_18
    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

    September 11-12, 2008 – Current Issues in Complex IP Licensing (Law Seminars International) – Philadelphia, PA

    September 15-16, 2008 – Biotech Patents (American Conference Institute)***

    September 22-23, 2008 – FDA Boot Camp (American Conference Institute)***

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

  • Boston Skyline American Conference Institute (ACI) will be holding its 10th Annual Forum on Biotech Patents on September 15-16 in Boston, MA.  The conference will allow attendees to:

    • Establish essential strategies to prepare their companies or clients in light of frenzied upheaval in the patent world;
    • Analyze the profound and potentially earth shattering ramifications of recent court decisions impacting patents, particularly Tafas/GSK v. Dudas;
    • Implement an effective working relationship with the USPTO to successfully manage their patent applications;
    • Identify problem behaviors that could result in a claim of inequitable conduct;
    • Maximize their patent strategy when considering Board of Appeals and Interference action;
    • Optimize their knowledge of the impact and ramification of potential follow-on biologics and antibody technologies in the patent arena;
    • Uncover the key to an effective global patent strategy in light of world-wide patent practices; and
    • Expand their skills in drafting, executing, and prosecuting biotech applications.

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

    Biotech_patents
    • Key biotech cases to watch and how they may impact your practice;
    • The industry speaks:  Maximizing your relationship with the PTO;
    • Navigating the Board of Patent Appeals and Interferences in light of the KSR decision;
    • Life on the patent tightrope:  Updates on the proposed rules and patent reform;
    • They are coming:  Preparing your practice for the inevitable insurgence of follow-on biologics and predicting the future of the biotech industry;
    • The international perspective:  Changing patent practices in the EU and India;
    • Practicing biotechnology arts:  Claim drafting strategies;
    Ex Parte Kubin:  A case study — to be presented in part by Patent Docs author Kevin Noonan;
    • Strategies and applications to implement during all stages of the biotech patent prosecution process to prevent allegations of inequitable conduct; and
    • Different but the same:  The unique nature of prosecuting antibody therapeutics applications under the standard patent prosecution process.

    An additional master class entitled: "Drafting Successful Patent Applications for Biotechnology Related Inventions" will be offered on September 17, 2008.  The master class will walk conference attendees through the process of drafting the claims and specifications for biotechnology applications related to inventions such as research tools, pharmaceuticals, genomics, proteomics and diagnostics, and provide attendees with tools to draft strong applications that will be well positioned to withstand future challenges.  In addition, the master class will cover issues that should be considered when drafting claims in the context of litigating or licensing patent claims related to biotechnology inventions to help attendees prepare patents and structure deals that provide real value.

    The agenda for the Biotech Patents conference can be found here.  A complete brochure for this conference, including an agenda, list of speakers, and registration form can be downloaded here.

    American_conference_institute_aci
    The registration fee ranges from $2,195 (conference alone) to $2,795 (conference and master class).  Those registering on or before July 21, 2008 will receive a $300 discount off the registration fee and those registering on or before August 18, 2008 will receive a $200 discount off the registration fee.  Those interested in registering for the conference can do so here, by calling 1-888-224-2480, or by faxing a registration form to 1-877-927-1563.

    Patent Docs is a media sponsor of ACI's Biotech Patents conference.

  • Boston Skyline American Conference Institute (ACI) will be holding the next session of its FDA Boot Camp conference on September 22-23 in Boston, MA.  The conference will allow attendees to:

    • Master the basics of the application and approval processes for drugs, biologics, and devices;
    • Comprehend the structure of the FDA and the roles of the CDER, CBER, & CDRH;
    • Develop a practical working knowledge of clinical trials for drugs and biologics and the clearance process for devices;
    • Appreciate the regulatory balance between brand name and generic products;
    • Understand the complexities of the patent and IP landscape, including the Hatch-Waxman Act, Orange Book, 180-day exclusivity, 30-month stay, Paragraph IV, NDA, ANDA, and 505(b)(2);
    • Recognize the role of labeling in the drug/biological product approval process;
    • See the importance of cGMPs to the post-approval regulatory process;
    • Navigate the protocols of adverse events monitoring, pharmacovigilance, and Risk Evaluation and Minimization Strategies (REMS);
    • Learn how devices are classified, monitored, and regulated; and
    • Explore the FDA's expectations and guidance for recalls.

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

    Fda_boot_camp
    • The basics:  Understanding and working with the FDA — jurisdiction, functions, organization, and operations;
    • The nature of the approval process;
    • Understanding the clinical trial process for drugs and biologics;
    • Patent and IP overview:  Hatch-Waxman, trade dress, and more;
    • Drugs and biological products:  Labeling;
    • cGMPs:  Drugs and biologics (current good manufacturing practices);
    • Non-patent exclusivity (part of the conference's patent track) — to be presented by MBHB colleague and Orange Book Blog author Aaron Barkoff
    • Bioequivalence:  What patent lawyers need to know (patent track)
    • Follow-on (comparable or biosimilar) biologics (patent track)
    • Adverse events monitoring, pharmacovigilance, and risk management;
    • Medical devices:  Classification and the essentials of the device premarket review process;
    • Post-market requirements and concerns for medical devices;
    • Medical device labeling and advertising; and
    • Recall guidance for drugs, biologics, and medical devices:  What you need to know.

    The agenda for the FDA Boot Camp conference can be found here.  A complete brochure for this conference, including an agenda, list of speakers, and registration form can be downloaded here.

    American_conference_institute_aci_2
    The registration fee for the conference is $2,195.  Those registering on or before July 18, 2008 will receive a $300 discount, and those registering on or before August 29, 2008 will receive a $200 discount.  Those interested in registering for the conference can do so here, by calling 1-888-224-2480, or by faxing a registration form to 1-877-927-1563.

    Patent Docs is a media sponsor of ACI's FDA Boot Camp conference.

  •     By Kevin E. Noonan

    Doll_john
    On Tuesday, U.S. Patent Commissioner John Doll (at right) touted several initiatives being pursued in the U.S. Patent and Trademark Office to reduce the backlog of pending cases (see "Lunch with Commissioner Doll").  He also said he (and the rest of PTO management) welcomed whatever creative ideas that the patent community has to solve the Office’s backlog problem.  Since we at Patent Docs believe Commissioner Doll is sincere (although occasionally misguided) in his passion for improving the U.S. patent system, we thought about his invitation seriously and have the following recommendations, based in part on what the Commissioner said "was working" among the current Patent Office initiatives.

    This proposal is based on many of the current initiatives in the office, including accelerated examination and efforts to promote examiner interviews as well as disclosure of "the best" prior art known to the Office and applicants.  In this proposal, the Office would offer applicants an incentive that for every application that an applicant abandons, another, related application would receive accelerated examination.  The related application receiving this benefit would be of applicant’s choosing, but would be limited to applications in which the remaining issues were scope issues (i.e., generally related to issues arising under 35 U.S.C. § 112) rather than prior art issues (i.e., relating to rejections under § 102 or § 103).  Applicants could make an application eligible for acceptance into the accelerated program by filing an amendment that would overcome any pending § 102 or § 103-related grounds of rejection.  In addition, for any application undergoing accelerated examination, any claims subject to restriction and eligible for rejoinder would be rejoined for examination.  Upon notice of accelerated examination, applicants would have to certify that they had performed a search, under PTO guidelines, and had submitted all art uncovered in the search or cited in any corresponding foreign patent office.  However, there would be no obligation for the applicant to characterize the references, and a presumption would arise that a search conducted under PTO guidelines satisfied the provisions of Rule 56.  There would be no time limitation on this form of accelerated examination, unlike the program currently in place that has a 12-month "filing to decision" goal; the applications in this program would be treated like reexaminations or under the former "petition to make special" practice (they would be treated with special dispatch and advance to the head of the examiner’s "to do" list).  Extensions of time to respond would be limited to good cause shown or unavoidable delay.  Applicants opting for this program would be entitled to an examiner interview after submitting the art, either with the primary examiner or a SPE having signatory authority, and with the goal of arriving at patentable subject matter as a result of the interview.

    Uspto_seal_no_background_1
    The benefits of the program are that at least one application would be abandoned for each application in the program; even if an applicant were to obtain a patent and file a continuation, the Office would have the benefit of reducing the backlog by two cases for every additional new one (the abandoned application plus the granted patent counting as two dispositions).  Moreover, presuming a fair percentage of the cases in the program would have divisional applications (the PTO’s rationale for the now-enjoined claims and continuation rules showed that about 40% of the "rework" applications were divisionals), there may be more than two dispositions for each additional continuation.  Assuming even 10% of the applications in the backlog would participate in the program, the overall reduction in the number of backlog cases could be on the order of 25%.  This trend could be accelerated by targeting applicants with large pending portfolios.  For example, IBM has a total of 23,731 published applications in the PAIR system, and Microsoft has another 12,507 applications.  The Office is certainly aware of other entities "responsible" for a large proportion of the backlog, and such entities could be reminded of the offer in all Office Actions or other Office correspondence they receive.  (The Office would have to make a determination whether it was worthwhile to include the offer to all applicants in all papers sent by the Office.)

    The program could also work for small entities, although it might be prudent to waive the requirement for abandoning related applications for these applicants.  This is because these applicants typically have far fewer applications contributing to the backlog, and accelerated examination might provide them with sufficient protection that related applications would no longer be necessary.  It is expected that the program would have little effect on "new technology" application filings.

    Unlike the now-enjoined new rules, the benefits of this proposal is that they are voluntary and so do not constitute a taking or other encroachment on an applicant’s rights or expectations and as such should be less exposed to judicial challenge.  For applicants, the proposal offers the benefits of reduced prosecution costs, reduced pendency times, and more focused PTO examination.  The Office benefits by reducing the backlog as well as having a larger percentage of applicants being involved in examiner interviews; Commissioner Doll reported that both examiners and applicants thought the interview process was the greatest benefit of the current accelerated examination program.  And the public benefits because the examiner will have had the "best" art available for examination and the best understanding of the invention through the interview process, thereby ensuring maintenance of high patent quality.  Transparency concerns could be met as they are now, by the requirement that the applicant provide an interview summary as part of any response filed after the interview.

    Commissioner Doll expressed a fairly negative view about blogs and bloggers, with perhaps some justification in view of the penchant for some to use their blogs as tools to criticize or "vent" their frustrations with the Office.  (It is likely denizens of the Office have the same needs, which are occasionally revealed in the commentary sections of some patent law blogs.)  However, blogs and bloggers are also people invested in the patent process, and who take the time to make proposals like this one as part of the patent community’s effort to contribute to solving the problems that actually exist in the U.S. patent system.  We hope that Commissioner Doll (or a minion) takes the time to think about what we propose here, at least as a starting place for addressing the very real problems that Mr. Doll has taken so much time and effort to emphasize in his formal dealings with the public.  There are ideas out here, Commissioner Doll; is anyone in the Office listening?

    For additional information on this and other related topics, please see Patent Docs‘ "Post GSK: Where Do We Go from Here?" series:

    • "Readers Propose Changes," January 8, 2008
    • "Accelerated Examination," November 13, 2007
    • "Deferred Examination," November 12, 2007
    • "Co-owned, Co-pending Applications," November 11, 2007
    • "Increased Fees for Continuations," November 8, 2007
    • "Regional Patent Offices," November 7, 2007
    • "Tailoring Protection and Examination," November 6, 2007
    • "Annuities," November 1, 2007

  •     By Donald Zuhn

    Mmm
    Earlier this month, the monthly healthcare marketing publication Medical Marketing & Media (MM&M) announced the release of The Pharma Report 2008, MM&M’s list of the top twenty pharmaceutical companies (as determined by U.S drug sales in 2007).  According to MM&M’s report, the top twenty pharma companies for 2007 were:

    1.  Pfizer – $23.52 billion
    2.  GlaxoSmithKline – $20.14 billion
    3.  Merck & Co. – $17.64 billion
    4.  Johnson & Johnson – $16.28 billion
    5.  AstraZeneca – $15.47 billion
    6.  Amgen – $14.34 billion
    7.  Novartis – $13.92 billion
    8.  Sanofi-Aventis – $10.87 billion
    9.  Eli Lilly and Co. – $10.28 billion
    10.  Abbott Labortories – $9.06 billion
    11.  Genentech – $8.76 billion
    12.  Wyeth – $8.61 billion
    13.  Teva Pharmaceuticals USA – $7.93 billion
    14.  Bristol-Myers Squibb – $6.87 billion
    15.  Boehringer Ingelheim – $5.76 billion
    16.  Schering-Plough – $4.69 billion
    17.  TAP Pharmaceuticals – $4.54 billion
    18.  Forest Laboratories – $3.87 billion
    19.  Hoffman-LaRoche – $3.58 billion
    20.  Takeda Pharmaceutical – $3.51 billion

    MM&M also took the opportunity to discuss the state of the pharma industry, noting that the U.S. drug market grew by only 3.8% in 2007 as a result of the loss of product exclusivity, low levels of product growth, and safety concerns.  Diana Conmy, of IMS Health (a pharmaceutical and healthcare consulting company), noted that "if you look at the top five companies, they are the folks that (also) have big blockbusters going off patent," and that "some of the safety issues are also prevalent within the top 10."  MM&M predicted that as larger drug makers are impacted by a number of 2008 patent expirations (see Figure 10 from the report; shown below), "smaller or mid-size drug companies may be better positioned to take advantage of the current marketplace due to their involvement in specialist-driven areas."

    Fig10_4

    The Pharma Report 2008, Medical Marketing & Media.

    The report also included a list of the top twenty prescription drugs by U.S. sales (see Figure 2 from the report) and a list of the top twenty therapeutic categories by U.S. sales (see Figure 3 from the report; shown below).

    Fig3

    The Pharma Report 2008, Medical Marketing & Media.

  •     By Kevin E. Noonan

    One of the frustrations of those opposed to actions taken by the Administration over the past eight years has been the lack of Congressional oversight, in view of the congruency of the party in power of the legislative and executive branches.  Although in theory this left the judicial branch to supply a check (or a balance) on public policy, the courts are a blunt and slow tool (and are not above their own type of partisan bias; see Bush v. Gore ).  However, this trend began to turn with the election of the members of the 110th Congress, where the opposition party came to power and, although lacking a sufficient majority to impose its will, maintains the power to police.

    B000410
    One part of the Administration that has suffered mightily as a result of this lack of oversight is the Patent Office, where the current Director and his minions have presided over one of the great adventures in mismanagement in U.S. history.  But it appears that at least some of the Members of Congress are beginning to notice:  at the end of April, Howard Berman (D-CA), Chairman of the Subcommittee on Courts, the Internet, and Intellectual Property of the House Judiciary Committee sent Jon Dudas, Director of the U.S. Patent and Trademark Office, a letter requesting information to supplement Director Dudas’ February 27, 2008 testimony before the subcommittee at an oversight hearing (see "House Subcommittee Holds USPTO Oversight Hearing").  Although on its face the letter was a cordial request for additional information, even the most casual perusal of the contents of the letter indicates that Congressman Berman (at right) has something on his mind.

    Dudas_jon
    The letter contains eighteen numbered paragraphs covering a wide range of topics.  And the questions are specific, asking Director Dudas (at left) to reconcile or justify his testimony with either Patent Office behavior, statements, or actions.  These topics include:

    • Projections as to the number of applications expected to be filed over the next five years.  The Congressman wants to know what methods (including computer programs) the Office uses to make these projections and what considerations are included in its calculations.  The letter specifically references the enjoined continuation and claims rules, and asks to what extent the projections were based on anticipation that the new rules would be implemented.  It also points out that the FY2008 budget projected an 8% per year increase, while the FY2009 budget projects a 5% per year increase.

    • In view of the status of the enjoined new rules, the Congressman asks what actions the Office and/or Congress could take to address the pendency backlog, either at a 5% per year or 8% per year patent application increase level.  The letter also cites the GAO Report that claimed the Office could hire 2,000 new examiners per year for the next five years and still not decrease the backlog (the GAO report estimates the backlog would continue to grow, under this scenario, from 260,000 in FY2007 to 953,643 at the end of FY2011).  The letter notes that the source of the GAO’s estimates was the PTO, and thus requests Director Dudas to provide all information supporting these estimates.

    • Turning to the corps of patent examiners, the letter cites statements in the GAO report alluding to internal Office review of production goals for examiners.  The letter then cites Director Dudas’ testimony before the subcommittee that the Office was beginning to review production goals.  Congressman Berman asks Director Dudas to provide a description of the methods being used to perform this review, the personnel involved in the review, and a timetable for its completion.  In this regard, the letter also asks for an accounting of the discrepancy between the GAO report’s statements, that most examiners who leave the Office do so in response to management (including the production goals), and Patent Office statements that most examiners leave the Office for "personal reasons."  The letter specifically asks questions regarding putative exit interviews given to departing examiners that Director Dudas used to support his testimony, including the percentage of departing examiners who had participated in said interviews.

    • Patent allowance statistics, specifically the decline in allowance rate from 70% in 2000 to 44% in 2007. The letter asks whether the Office included Requests for Continued Examination in its statistics, and if so how.

    • The letter requests further information on the progress of plans for regional patent offices, and asks what resources have been used, particularly in view of the failure of the program to be included in the FY2009 budget.

    The letter turns more frank with regard to two issues:  the statutory requirements for making changes in the Office’s internal management structure, and the behavior of "senior PTO officials" in the RIM v. NTP reexamination.

    • The letter also asks for information regarding whether the Office violated Acts of Congress as well as Commerce Department rules when implementing the creation of the Office of Enforcement.  Specifically, the letter reminds Director Dudas that the 2006 Science, Justice, Commerce Appropriations Act requires that, before the Office can "reprogram" funds it must notify Congress fifteen days prior to reprogramming, and that Departmental Administrative Order (DAO) 203-13 defines reorganization ("establishment, consolidation, abolition or ‘other significant change’") as "generally considered a reprogramming that triggers the disclosure requirement."  Director Dudas had testified to the subcommittee that elimination of the Office of Enrollment was a "realignment," and the letter requests the Director to inform the subcommittee of the criteria used to distinguish between the two.  In this regard, Congressman Berman asks the Director for an accounting of all other actions taken by the Office that were deemed a "realignment" (and putatively outside the rule requiring Congressional notification) and a "detailed description" of the basis for so doing in each instance.

    • The letter cites an article in Time magazine from 2006 and an e-mail from James Toupin that "senior Administration officials" met with RIM’s CEO Jim Balsillie during the pendency of the NTP reexamination.  Calling it "ex parte activity," the letter asks Director Dudas to identify all senior Patent Office personnel involved in such meetings, and for the Office’s policy regarding these contacts.

    I000056_2
    The answers to these questions should be interesting indeed.  Also included in the letter are even more pointed questions posed by Congressman Darrell Issa (R-CA), a subcommitee member:

    • Congressman Issa (at right) wants to know the policy basis for the Office to eschew implementing a "request for examination" requirement, as a way to reduce the backlog based on the experience in other countries that "10% to 40%" of all applications are allowed to lapse for failure to request examination.

    The letter gives Director Dudas until May 19, 2008 to provide answers to these questions, pointedly including the subcommitee’s address (B-352 Rayburn House Office Building, Washington, D.C. 20515).

    While these actions are to be applauded, they carry with them the feeling of being too little, too late.  The same "senior Patent Office officials" responsible for the ineffectiveness of the Office to address its problems will be leaving in less than twelve months, and those who willingly and enthusiastically fell into step behind their misguided proposals may be expected to leave as well.  The legacy of these officials, like so much of the rest of the current administration, will be of opportunities lost, squandered by an appeal to authoritarian rulemaking rather than consensus building with Patent Office stakeholders.  In view of the current parlous state of the USPTO, Inauguration Day 2009 (fittingly, a PTO holiday) can’t get here soon enough.

    ADDENDUM:  For a chilling set of allegations of misconduct in the NTP patent reexaminations (the subject of one of Congressman Berman’s inquiries to Director Dudas), we direct our readers to the last twenty pages or so of NTP’s response, filed April 24, 2006 in Re-examination Control No. 90/007,731, 90/006,675, and 90/006,533 (consolidated) (see Patently-O link).  NTP alleges multiple acts of misconduct against senior administration officials (including Director Dudas and Commissioner Doll), based on e-mail correspondence and other documents obtained under a Freedom of Information Act request.  (Thanks for Peter Zura’s 271 Patent Blog for alerting us to these allegations.)

  •     By Donald Zuhn

    Stemcells
    Earlier this week, we reported on two recently filed patent cases:  the first by StemCells, Inc. against Neuralstem, Inc., asserting infringement of U.S. Patent Nos. 7,115,418 and 7,361,505, and the second being filed by Neuralstem, seeking a declaratory judgment of noninfringement, unenforceability, and invalidity of the ‘505 patent.  The ‘505 patent, which is directed to multipotent neural stem cell compositions, was issued on April 22, 2008.

    Neuralstem
    In a May 7th press release concerning its declaratory judgment filing, Neuralstem stated that StemCells "intentionally withheld crucial information highly material to the patentability of StemCells’ ‘new’ patent," and did so with an intent to deceive the USPTO.  In particular, Neuralstem asserts in its complaint that StemCells failed to disclose "pending litigation with Neuralstem, the reexaminations filed by Neuralstem, and the prior art cited in those reexaminations" (the litigation and reexaminations are discussed below).  With respect to the prior art cited in the reexaminations, Neuralstem contended that the art was cited, but only after the issue fee for the ‘505 patent had been paid.  Neuralstem President and CEO Richard Garr contended that while "it is clear that we are not infringing this patent, . . . the threatening statements in [StemCells’] press release of April 23rd leave the misleading impression that we would require a license from them as a result of the issuance of this patent," and "[n]othing could be further from the truth."

    The newly filed cases do not mark the first time that the two companies have squared off in court.  In 2006, StemCells filed suit against Neuralstem, asserting infringement of four other neural stem cell patents.  Neuralstem responded to that suit by filing requests for ex parte reexamination of all four of the asserted patents.  Last month, the U.S. Patent and Trademark Office issued a Notice of Intent to Issue an Ex Parte Reexamination Certificate for two of the four StemCells patents.  The two companies quickly issued competing press releases asserting that the USPTO had upheld the patents with only minor changes (according to StemCells) or with "numerous substantial changes" (according to Neuralstem).

    On May 6th, Neuralstem announced that it had filed a motion to reopen the 2006 lawsuit, which had been stayed pending the outcome of the reexamination proceedings.  Neuralstem CEO Richard Garr contended that "the recent actions of the U.S. Patent Office now entitle [Neuralstem] to summary judgment in the case," and that "[c]ompletely contrary to the public statements made by StemCells, Inc., the Patent Office actions have destroyed the basis for the infringement suit filed by StemCells, Inc."  In a May 12th press release, Neuralstem reiterated its position "that actions of the Patent Office have destroyed the basis for [StemCells’] infringement assertions against [Neuralstem]."

    In response to Neuralstem’s May 7th press release, StemCells issued its own statement, announcing that it had filed suit against Neuralstem in the Northern District of California with claims for patent infringement, libel, and unfair competition.  In its statement, StemCells contended that "Neuralstem’s repeated false statements and public accusations over the past year, culminating in its allegations on the procurement of the ‘505 patent this month, together with its continued and willful infringement of StemCells’ intellectual property, necessitated the Company’s California action."  In response to Neuralstem’s assertion that StemCells was unwilling to reopen the 2006 (implying that the reexamination result had been less than favorable for StemCells), StemCells President and CEO Martin McGlynn stated that "[o]nce the reexaminations of all [four] patents have been fully settled, we will move to reopen the Maryland litigation and have our day in court."  For now, it appears that the battle between the two companies is far from over.

    For additional information about this and other related topics, please see:
    • "Neuralstem Announces Grant of European Patent for Neural Stem Cells," April 30, 2008
    • "StemCells Announces Issuance of Human Neural Stem Cell Patent," April 24, 2008
    • "StemCells’ Patents Survive Reexam — StemCells and Neuralstem Differ on Extent of Changes," April 22, 2008

  •     By Kevin E. Noonan

    Doll_john
    John Doll, Commissioner for Patents of the U.S. Patent and Trademark Office, gave a luncheon seminar today concerning the state of the USPTO, hosted by the Boston office of Kirkpatrick & Lockhart Preston Gates Ellis LLP.  As we’ve said before, Commissioner Doll (at right) is the happy face of the U.S. Patent and Trademark Office:  smiling, self-deprecating, and charming while he espouses the Patent Office mantra that the Office is willing to do everything possible to improve the patenting process in the United States.  Today’s offering was no different.

    Uspto_seal
    The Commissioner touted a number of programs and policies in the Office intended to address the twin goals of reducing the backlog of unexamined applications and improving the quality of granted patents.  The first initiative Commissioner Doll mentioned was the accelerated examination (AE) program, which he considers an unqualified success.  The statistics he cited bear him out:  110 patents have been granted under the program, and the goal of filing to final disposition (abandonment, grant, or exit from the program for appeal or further prosecution) within a year has "never" been missed.  One unnamed patent was particularly speedy:  allowed within 17 days of filing and granted 58 days thereafter (75 days filing to grant).  Use of the program is accelerating, with 200 applications filed requesting AE in the past month.  Commissioner Doll confessed that his intuition about what would be the most important component of the program – the Examination Support Document, in which the results and detailed analysis of an applicant-performed search are submitted to the Office – was wrong; both applicants/practitioners and Examiners report that it is the interview that makes the greatest difference.

    This result has led to a second program initiative, the "interview before first action" program (see "PTO Announces New Program to Reduce Pendency and Improve Patent Quality").  After the Examiner has performed a search, participants can have an interview to discuss the art.  Thereafter, the expectation is that the Examiner will be able to mail an allowance or a first action on the merits, which will be (presumably) the parts of the interview where the examiner and applicant could not reach agreement.  Such interviews have been available for many years.  (For many law firms, one of the purported advantages of a Washington, D.C. office in the old, cooperative days of the Patent Office was the ability to walk down the street and meet with an examiner to discuss an application prior to first action.  This practice was discouraged over the past few years, since it resulted in many instances with a first action allowance and a patent having essentially no prosecution file history.)  The pilot program is limited for now to the computer database arts; the Commissioner referred the curious to the PTO website for more information (alternatively, the curious could refer to the Patent Docs post on this pilot program).

    The Commissioner announced a major initiative to bring the Office into compliance with its responsibilities under the Patent Cooperation Treaty, specifically with regard to its status as an International Searching Authority.  The Office currently complies with the time limits for providing a Chapter I search about 4% of the time.  There are currently 17,000 PCT applications unacted upon (i.e., no search has been performed).  The goal is to have these applications searched by the end of the calendar year, and to bring the Office into 80-90% compliance as soon as possible.  While admirable, the way this is being done may be problematic:  the Office has outsourced searching to two professional search firms for the 17,000 "backlogged" PCT applications, and intends to outsource 100% of PCT searching.  While not controversial in and of itself, it seems that these searchers will also be responsible for determining (and denoting on International Search Reports) whether a reference is novelty-destroying (an "X" reference) or precludes inventive step (a "Y" reference) according to the provisions of PCT Article 33.  This raises the question of whether these searchers are competent to make these determinations, and whether the Office has abandoned its responsibility to provide a proper PCT search.  Ironically, the Commissioner also stated that he thought such searches should be "fee neutral" to the Office – raising the possibility that applicants would be charged additional fees under the PCT for searches that may not be PCT-compliant.

    Commissioner Doll next addressed the issue of examiner hiring efforts.  The Office has hired 1,200 new examiners each year for the past few years and will be doing so for the next few years, and these efforts will have swollen the examiner ranks to about 6,000 at the end of FY2008; this number is expected to reach 8,000 by the end of FY2010.  Since attrition has been a problem (in the "two steps forward, one step back" sense) with the examiner corps, the Commissioner was happy to say that overall attrition rates are at 8.5%, a number he compared favorably both with Federal government employees overall (11.2%) and employees at high-tech industries.  It also seems that the likelihood of becoming a Patent Office "lifer" goes up dramatically after these first three years; while the attrition rate for "new" examiners (those with less than 3 years on the job) was 15.5%, the attrition rate for years 4 through 30 is only 4%.  To increase the likelihood that examiners stay long enough for these statistics to apply, the Office has instituted a number of financial and lifestyle incentives.  Retention bonuses are the most naked form of gentle coercion (he did not specify the amount of these bonuses); in addition, the Office has instituted overtime and quality bonuses (the latter subject to negotiation with POPA).  There are also programs for "flat goal" work, where the examiner can commit to a certain production level (with, presumably, adjustments in salary for performance below the standard requirements); the Office will pay bonuses of up to $20,000 plus 3% of their base pay for those examiners exceeding the goal.  On the lifestyle side, the Office has a "hoteling" program, where examiners can work remotely.  An impediment to greater use of this program is the requirement (under Federal law) that employees must "report to their station" once a month.  The Commissioner mentioned a bill pending in Congress (S. 1000) that would loosen that requirement.  Finally in this regard, giving laptops to examiners having GS9 seniority or greater has almost doubled the amount of overtime these examiners work.  All of these initiatives are directed, according to Commissioner Doll, to effecting a reduction in the backlog.  Interestingly, another aspect of the Office’s focus on the backlog is that the Office is targeting its examiner hiring to those art units most in need of backlog reduction.

    Dudas_jon
    A program that the Commissioner ascribes to Director Jon Dudas (who is "aggressively pursuing it") is a "worksharing" program, that is an offshoot of the Patent Prosecution Highway programs currently in place with the Japanese Patent Office and other offices, and soon to be established with the EPO.  The Commissioner drew a distinction between the programs, however, saying that the PPH program was "applicant-initiated" while the proposed worksharing program would be Office-initiated.  Under the PPH, an applicant having an examination in one office can have the results transmitted to a second PPH office, to expedite prosecution in the second office based on (successful) prosecution in the first office.  The worksharing program would also permit examination results to be transmitted between offices, although it can be expected that the offices will not have the applicant’s incentive to transmit only positive prosecution results.  Commissioner Doll was particularly hopeful about the economies of scale that could be achieved by having available to the U.S. Office results of a Japanese Patent Office search of Japanese patents and applications (which are rarely a major part of the prior art considered during U.S. prosecution), and envisioned a "common" prior art database that could be used by Peterlin_maragret_3
    all offices.  An amusing aspect of this program is the establishment of a PTO "Facebook" so examiners at the different offices can "get to know one another."  The worksharing idea will be further discussed in a meeting between the "Big 5" offices (the USPTO, EPO, JPO, Korean Patent Office and Chinese Patent Office) chaired by Deputy Director of the USPTO Margaret Peterlin, to be followed by a Director level meeting in several months.  Importantly, at least as currently proposed there are no "full faith and credit" provisions for one office to another.

    The last part of Commissioner Doll’s prepared remarks was a brief encomium to the EFS-Web electronic filing system, which has increased users from 2% to 70% over the past two years.  Calling those not using the program "technology dinosaurs," he offered to do whatever it takes to help those to get with the program.

    Commissioner Doll’s comments during the Q&A session were not particularly remarkable, except insofar as he stated that the now-enjoined new continuation and claims rules were never viewed as a "silver bullet" for solving the backlog problem.  He reported that the rate of increase in the backlog had slowed (to about 40,000 applications for FY2008), and suggested that the Office had not "given up" on the other pending rules packages (Markush, IDSs, biological deposits) that have been subject to public comment.  He strongly supported provisions of pending legislation that would give the Office fee-setting authority, and hinted that if they got it they would use it to establish disincentives to current continuation practice.  He repeated the Office policy that the "best" application was one where the applicant presented the "best" claims upon initial filing and came to an ultimate resolution in that case, and said the best way for that to happen would be if the Office could impose the Applicant Quality Statement obligation contained in S. 1145.  Using his "crystal ball," he predicted that the growth rate of new filings would be about 5% in FY2008 and at the same level over the next few years.  He characterized this as "healthy," saying that the variances in application filing rates of the last 20 years average about 6.5%, with some years being as high as 25% and others close to zero.  He opined that the Supreme Court’s KSR decision might influence filing rates, and defended how the examining corps was applying PTO guidelines on implementing the KSR decision.  He also asserted that the Office had trained "every" examiner on the new guidelines.

    Toupin
    With regard to patent reform legislation, Commissioner Doll said Deputy Director Peterlin and USPTO General Counsel John Toupin (at right) were on the Hill "almost daily" working for the legislation, and said the AQS provision was on his "wish list" as the single change that would improve patent quality.  He cautioned against "dumping" too much irrelevant material on the Office in the guise of an IDS, and used two examples.  One was the prosecution history of related applications, where merely filing the entire file history was disfavored.  Also a Patent Office no-no would be filing "boxes and boxes" of material from litigation (seemingly unaware that generating boxes and boxes of material is what happens in patent litigation).  He was similarly unconcerned about the risks of inequitable conduct allegations even for practitioners diligently attempting to comply with Rule 56, and backed Harry Moatz’s interpretation of 37 C.F.R. § 10.19 that a practitioner is required to review every page of every reference submitted to the Office.

    There was one note of disingenuousness in Commissioner Doll’s responses.  He was asked whether a Quality Review official could overrule an examiner.  He said the quality reviewer merely provided a recommendation, because the statute gives primary examiners the authority to decide whether to allow a case, and a Supervisory Examiner (SPE) or even the Commissioner did not have the power to overrule them.  This could be the basis for an important practice tip, except that in the next breath he said that where there was a genuine disagreement with a primary examiner, the examiner could either withdraw the notice of allowability or the SPE would transfer the case.  Even though he said this occurs very rarely (twice in his 33 years, and he was decent enough to admit that in one case the applicant appealed and the Board sided with the applicant), it is perhaps an illustration of his limitations as Commissioner that he obviously didn’t see how he had enunciated a distinction without a difference (i.e., that supervisory personnel exercise de facto veto power over the primary examiners).

    Not surprisingly (but a little disappointingly), Commissioner Doll is not a big fan of blogs.  While he later backed off his original characterization of bloggers as people without enough to do, in fairness the question was asked with regard to websites that "rate" examiners.  Although understandable in thinking that it was more likely to contain brickbats than kudos, he has obviously not read one lately; there are a surprising number of bouquets among the criticisms, perhaps reflecting real differences between different examiners (which is something you’d think he would want to know).

    Commissioner Doll said he valued the kind of face-to-face discussions like today’s meeting to discuss how to improve the patenting system.  While that is certainly true, his ardor cannot hide the fact that the actions of the Patent Office over the past few years suggests to many that no one is listening to the patenting community.

  •     By Christopher P. Singer

    Written_description_training_materi
    Last month, the U.S. Patent and Trademark Office announced
    that it had updated the training materials to be used by examiners in
    the examination of patent applications for compliance with the written
    description requirement of 35 U.S.C. § 112, first paragraph.  The revised training materials supersede and replace the previous set of training materials
    issued by the Patent Office in 1999.  The new training materials
    provide seventeen examples, of which fourteen are specifically related
    to biotech inventions.  In particular, the biotech-specific examples
    address expressed sequence tags (ESTs) (example 4), a partial protein
    structure (example 5), DNA hybridization (example 6), allelic variants
    (example 7), bioinformatics (example 8), protein variants (example 9),
    a product claimed by its function (example 10), a polynucleotide or
    polypeptide sequence sharing percent identity with another sequence
    (example 11), antisense oligonucleotides (example 12), antibodies to a
    single protein (example 13), antibodies to a genus of proteins (example
    14), a genus with widely varying species (example 15), a process claim
    where novelty resides in the process steps (example 16), and methods of
    using compounds claimed by functional limitations, methods of
    identifying compounds, and compounds identified by such methods
    (example 17). Continuing our review, Patent Docs provides an overview of the example covering aspects of antisense oligonucleotides.

    Example 12 – Antisense Oligonucleotides

    Example 12 relates to claims directed to an antisense oligonucleotide complementary to an mRNA that encodes a "newly discovered growth factor" (NDG).  This Example is essentially identical to the guidance in the former written description guidelines (presented therein as Example 15).  The exemplary claim in the new training materials recites:

    Claim 1:  An antisense oligonucleotide complementary to all or a portion of a messenger RNA having SEQ ID NO: 1 and encoding NDG, wherein said antisense oligonucleotide inhibits the production of NDG.

    The hypothetical specification provides the mRNA sequence encoding NDG as SEQ ID NO: 1 and states that the invention includes antisense oligonucleotides that inhibit NDG production.  While no sequences of such antisense oligonucleotide are provided in the specification, it does describe several art-recognized screening methods for identifying target mRNA sequences for candidate antisense molecules (e.g., gene walking, randomized oligo libraries, and DNA arrays).  The specification also describes the use of chemically modified nucleotides that reduce the amount or rate of degradation by nucleases.  While the specification fails to provide any explicit example of an antisense oligonucleotide to SEQ ID NO: 1, the training materials reason that one of skill would understand that complementary sequences that approach the full length of an mRNA (such as SEQ ID NO: 1) are more likely to have antisense activity as compared to smaller sequence fragments.  Therefore, one of skill would acknowledge that the specification does provide one species of the claimed genus, that being the full-length complement to SEQ ID NO: 1.  Moreover, the structure of all possible antisense oligonucleotides falling within the scope of the claim are bound and limited by the full-length complement to SEQ ID NO: 1.  Given the art-recognized correlations between antisense function and structure of the target mRNA (e.g., as provided by certain computer mRNA modeling software packages), certain fragments having antisense activity can be identified and screened to confirm or assess inhibitory activity.  Thus, when the high level of skill and knowledge in the art relating to antisense technology is combined with the disclosure of an mRNA sequence (SEQ ID NO: 1), there exists sufficient written description support for the full scope of claim 1.

    For additional information on this topic, please see:

    • "Antibodies to a Single Protein & Antibodies to a Genus of Proteins," May 12, 2008
    • "ESTs & Partial Protein Structures," May 8, 2008
    • "DNA Hybridization & Percent Identity," May 6, 2008