Patent Docs

Indian Generic Drug Maker Seeks to Invalidate Cancer Drug Patent

February 29, 2008

By Kevin E. Noonan —

The latest skirmish in the struggle between innovator pharmaceutical companies (mostly in the Western world) and developing world populations is being played out in India. The outcome will depend on how the Delhi High Court interprets provisions of Indian patent law enacted to implement India’s compliance with provisions of the international Trade-Related Aspects of Intellectual Property Rights (TRIPS) agreement on intellectual property.

Roche is the Western innovator pharmaceutical company, Cipla is the Indian generic drug company (the largest) and the drug is erlotinib (trade name, Tarceva), a drug used to treat lung cancer. Roche has an Indian patent on the drug, obtained under patent laws revised in 1995 upon India’s accession to the TRIPS agreement. Cipla has ignored the patent and is producing and selling erlotinib (under the name Erlocip) in India, the first time this kind of blatant infringement has happened. Roche has asked the High Court for an injunction to prevent Cipla from continuing to sell its infringing form of the drug.

Countervailing Indian patent law are the economic realities: Roche’s drug costs $125/tablet (about $45,000 US per year), while Cipla’s drug costs much less ($42/tablet). Cipla’s position is that Roche’s patent is invalid; the application was originally filed in 1995, and while patents filed in 1995 or later were deemed to be valid by operation of Indian law in 2005, Cipla contends that only Indian patents filed in 1996 or later are valid because there was a one-year grace period to implement TRIPS, according to Yusuf K. Hamied (at right), Cipla’s chairman.

Tarceva is also under attack by another Indian generic drug manufacturer, Natco Pharma, which is seeking a compulsory license under Indian patent law to produce its generic version of the drug. Natco’s application is for permission to export 30,000 tablets of the drug to Nepal; for the privilege Natco is willing to pay Roche a 5% royalty. However, such a compulsory license, while permissible under Indian law, cannot be granted until three years after the innovator is granted an Indian patent (and thus should not be available until July 2010).

This is not the first time Natco has challenged a Western drug company with an Indian patent on a pharmaceutical product: Natco was the company that challenged Novartis over its Gleevec patent, and won.

The issue, of course, is cost, and the political pressure on governments in developing countries like India make it unlikely that such governments will be able to resist pressure from their own citizens in favor of multinational drug companies like Roche. In view of modifications to the TRIPS agreement, most notably the Doha declaration, such governments can effectively eat their cake and have it too, since Doha and other TRIPS provisions have created "loopholes" in intellectual property protection for medical emergencies and life-saving drugs (see "The Law of Unintended Consequences Arises in Applying TRIPS to Patented Drug Protection in Developing Countries"). While initially confined to anti-AIDS drugs, the scope of how these provisions are being applied has been expanded to include other drugs by countries like Thailand, who last year included Plavix® as one of the drugs granted a compulsory license by its government to (foreign) generic manufacturers.

Drug prices being the key motivator for governments in the developing world to grant such compulsory licenses, it would seem prudent for companies to lower their own prices and thus blunt if not forestall the generic companies’ justifications for government action. While this has happened sporadically in the past, there has been no coordinated effort by Western drug companies to develop a strategy around drug pricing in the developing world to address the compulsory licensing issue. Actions such as the ones contemplated in India and elsewhere make it apparent that such a coordinated strategy is necessary if innovator drug companies are not to be left with none of the advantages that the TRIPS agreement was intended to have for their industry.

For information regarding this and other related topics, please see:

• "Novartis to Supply Cancer Drug to Thai Patients," February 5, 2008
• "Neocolonialism in the Current Global Drug Pricing Regime?" August 19, 2007
• "More on the Global Drug Patenting Crisis," August 14, 2007
• "EU Trade Commissioner Sends Warning Letter to Thailand," August 13, 2007
• "Trying to Find a Solution to the Global Drug Pricing Crisis," July 16, 2007
• "Pharma Sanity Lacks Global Reach," July 13, 2007
• "Brasil Prevails in Dispute with Abbott over AIDS Drug Pricing," July 9, 2007
• "Africa (Still) Depending on the Kindness of Strangers in Anti-AIDS Drug Pricing," May 29, 2007
• "U.S. Trade Policy Becoming Less Pharma-Friendly," May 18, 2007
• "The "Unfairness" of World Intellectual Property Protection According to The New Yorker," May 17, 2007
• "Worldwide Drug Pricing Regime in Chaos," May 9, 2007
• "Not Getting It about Patented Drug Prices at The Wall Street Journal," May 6, 2007
• "A Modest Proposal Regarding Drug Pricing in Developing Countries," May 2, 2007
• "The Law of Unintended Consequences Arises in Applying TRIPS to Patented Drug Protection in Developing Countries," May 1, 2007
• "Abbott Agrees to Offer AIDS Drug at Reduced Price," April 12, 2007
• "No New Abbott Medicines for Thailand," March 14, 2007
• "More Compulsory Licensing in Thailand," February 1, 2007
IPO Conference on Recent IP Decisions

February 29, 2008

The Intellectual Property Owners Association (IPO) will be holding a conference entitled "Recent Decisions: How They Affect Your Corporate IP Practice" on March 17, 2008 in Washington, DC. Topics to be addressed at the conference include:

• Changes in Patent Jurisprudence: The Aftermath of KSR — litigation and prosecution panels
• Willfulness and Opinions of Counsel as Affected by In re Seagate
• Licensing and Cease & Desist Letters in Light of Medimmune
• Global Litigation Strategies and Extraterritorial Patent Enforcement
• Fraud before the U.S. Patent & Trademark Office
• Trends in Federal Circuit Damages Decisions

The conference's luncheon speaker will be Judge Kimberly A. Moore of the U.S. Court of Appeals for the Federal Circuit.

A complete brochure for this conference, including the conference program, a list of speakers, and registration form can be downloaded here.

The registration fee ranges from $750 (for IPO members) to $1,100 (for non-members). Those interested in registering for the conference can do so here.
23rd Annual ABA Intellectual Property Law Conference

February 29, 2008

The American Bar Association (ABA) section of Intellectual Property Law will be holding the 23rd Annual Intellectual Property Law Conference on April 10-12, 2008 in Arlington, Virginia. Among the topics that will be covered at the conference are:

• Are the Supreme Court and Federal Circuit on the Same Page For Patent Law?
• What Patent Law Reform Really Means For You
• Latest Developments in the U.S. Patent Office
• Litigation Skills – Representing Unpopular Defendants in IP Litigation
• Patent Trolls: Are They Down for the Count?
• Death and Texas: How to Survive and Thrive in Patent Litigation in the Eastern District
• Ethics Issues Part I: latest Developments in IP Litigation Ethics
• Breaking News – Hot Topics in Copyright, Trademark and Patent Law

On the first day of the conference, the luncheon speaker will be Chief Judge Paul R. Michel of the U.S. Court of Appeals for the Federal Circuit, who will discuss patent law reform. In addition, an evening reception will be held at the U.S. Court of Appeals for the Federal Circuit.

The program schedule for the conference can be found here. A complete brochure for the conference, including the program schedule, a list of speakers, and registration form can be downloaded here.

The registration fee ranges from $245 for students to $795 for non-ABA members. Those registering before March 26 will receive a $50 discount. Detailed registration information can be found here.
PharmaBiotech IP Summit

February 29, 2008

The 2008 PharmaBiotech IP Summit, organized by Worldwide Business Research, will occur in Philadelphia at the Ritz-Carlton, May 28-30. The conference, "Protect Critical Patents and Drive Sustainable Growth Through IP-Driven Business Strategies," consists of two main conference days and a master class. The Patent Protection and Enforcement Masterclass occurs on May 28, and covers topics such as the upcoming regulations, lifecycle extension relative to assessing best time to file applications, the new IDS rules, changes to Markush practice, avoiding inequitable conduct in prosecution, and the Examiners' guidelines on obviousness.

According to the conference website, the Summit will enable its attendees to:

• Effectively navigate recent and potential regulatory changes to ensure long term protection and enforcement of your patents.
• Enhance strategic management of your portfolio to get the best out of it.
• Implement innovative ways to extend the useful life cycle of your most commercially valuable assets.
• Meld IP and business strategies to become a true partner of the business and drive future growth.

CLE credit is available. For more information, including the agenda and registration information, visit the PharmaBiotech Summit IP website.
More on House Subcommittee USPTO Oversight Hearing

February 28, 2008

By Donald Zuhn —

Yesterday, we reported on the oversight hearing on the U.S. Patent and Trademark Office held by the House Subcommittee on Courts, the Internet, and Intellectual Property. The Subcommittee heard statements from Jon Dudas, the Undersecretary of Commerce for Intellectual Property and Director of U.S. Patent and Trademark Office; Robin Nazzaro, the Director of National Resources and Environment for the U.S. General Accountability Office; Robert Budens, the President of the Patent Office Professional Association (POPA); and Alan Kasper, the First Vice President of the American Intellectual Property Law Association (AIPLA) and a partner with Sughrue, Mion, PLLC. On Wednesday, we discussed Director Dudas’ testimony. Today, we address Mr. Kasper’s statement.

Mr. Kasper’s testimony touched on a number of topics, including prosecution cost, pendency, and quality; patent examination issues; Industry Trilateral initiatives; the Office’s disciplinary rules and inequitable conduct; and the Office’s new rules packages. In an opening discussion on the determination of claim meaning, Mr. Kasper (at left) asserted that the adverse effects of inequitable conduct charges and restricted claim scope caused by the application of principles such as prosecution history estoppel resulted in "a reluctance on the part of Applicants and their representatives to identify the relationship between claims and the original disclosure, to characterize the invention and the prior art during prosecution, and to explain the basis for amendments to the claims during prosecution."

On the topic of prosecution cost, pendency, and quality, Mr. Kasper acknowledged the difficulties faced by the Patent Office in processing increasing numbers of patent applications, but criticized the Office for failing to carry out initiatives identified in its draft Strategic Plan for FY 2007-2012 (published on August 24, 2006 at 71 Fed. Reg. 50048). Mr. Kasper stated that "[w]hile many of the initiatives identified in the Strategic Plan . . . were focused on quality, the main focus of the programs subsequently announced by the USPTO is on the establishment of additional responsibilities and restrictions on Applicants." Mr. Kasper then proceeded to identify "a number of problems that those of us on the front lines of patent practice have experienced," as well as proposed solutions for addressing these problems.

With an eye towards reducing prosecution costs and pendency, Mr. Kasper suggested that the Office encourage its examiners "to propose claim amendments that would, at least in the Examiner’s view, distinguish the claimed invention over the prior art." According to Mr. Kasper, the Office’s current production goal system created "a reluctance on the part of the Examiner to suggest or even commit to further claim limitations or modifications that would result in allowable claims and thereby shorten the prosecution process," leaving applicants "to guess what an Examiner might accept, and then file a Response with the hope that the Examiner does not find some further, previously undisclosed interpretation of the claims or the prior art that results in yet another rejection."

Mr. Kasper added that the "often unnecessarily technical and rigid" review of papers submitted by applicants also led to prosecution waste and inefficiency. He cited Notices of Non-Compliant Amendments that were being issued for the improper use of claim identifiers such as "currently amended" or "previously presented," and suggested that a more practical solution would be to allow such errors to be corrected by examiner’s amendment. According to Mr. Kasper, the Office’s rigid approach of dealing with formalistic errors by applicants stood in "dramatic contrast to the manner in which it treats the formalities governing communications by the Examiner with Applicants."

On the topic of pre-appeal conferences, Mr. Kasper criticized the Office’s use of pre-appeal panels comprising the original examiner and supervisor and a third examiner, since the third examiner occupies "a minority position from the beginning." Instead, pre-appeal panels should comprise at least two senior examiners not involved in the prosecution of the application for which pre-appeal review has been requested.

Moving to the Office’s proposed disciplinary rules, Mr. Kasper argued that the Office of Enrollment and Discipline’s (OED) requirement that practitioners submitting papers "must read each paper in its entirety, regardless of the source" would be "burdensome at best, extremely expensive, and ultimately of little or no benefit to the Office or the Examiner." In addition, Mr. Kasper criticized the Patent Office for failing to allow for public comment on changes in its disciplinary practices. No doubt also speaking about the House’s inclusion in its patent reform bill of broad Patent Office regulatory authority, Mr. Kasper described the proposed disciplinary rules as an indication of "the dangers and damage that can be caused where highly sensitive and legally significant issues are addressed by the USPTO prior to any public vetting and opportunity for input."

Addressing the Office’s new rules packages on continuations and claims, Information Disclosure Statements, appeals, and multi-invention alternative claims, Mr. Kasper offered to work with the Patent Office to find solutions to the pendency and quality problems identified by the Office. However, Mr. Kasper stressed that "[a] key to any solution . . . is the avoidance of requirements that foster charges of inequitable conduct or force undue limitations on the scope of protection that can be provided for an invention."
(Finally) It May Be Time to Stop the Hypocrisy over Stem Cell Patents

February 28, 2008

By Kevin E. Noonan —

The U.S. Patent and Trademark Office rendered its final decision on Monday in one of the re-examinations of the Thomson stem cell patents provoked by two groups: the Public Patent Foundation (PUBPAT), headed by Dan Ravicher, and The Foundation for Taxpayer and Consumer Rights (FTCR), a California taxpayer group. The Patent Office decision comes in the inter partes (35 U.S.C. § 311-318) re-examination of U.S. Patent No. 7,029,913.

The inter partes requesters had asserted four grounds of unpatentability against the claims of the ‘913 patent:

• That the claims are unpatentable under 35 U.S.C. § 103(a) for being obvious in light of the Robertson ’83 reference (Cold Spring Harbor 10: 647-63) in view of the Loring Declaration (see "It’s Time to Stop the Hypocrisy over Stem Cell Patents – Part I").
• That the claims are unpatentable under 35 U.S.C. § 103(a) for being obvious in light of the Piedrahita 1990 reference (Theriogenology 34: 879-901) in view of the Loring Declaration.
• That the claims are unpatentable under 35 U.S.C. § 103(a) for being obvious in light of the Robertson ’83 reference, the Robertson ’87 reference (Teratocarcinomas and Embryonic Stem Cells: A Practical Approach, IRL Press) and the Piedrahita 1990 reference in view of the Loring Declaration.

As set forth in the decision, the Examiner refused to adopt any of these grounds of unpatentability, since they improperly relied on the Loring declaration (which does not properly form a basis for re-examination). The Examiner instead raised the following grounds of unpatentability:

• That the claims were unpatentable under 35 U.S.C. § 102(b) for being anticipated by U.S. Patent No. 5,166,065 to Williams, either alone or based on evidence of inherency.
• That the claims were unpatentable under 35 U.S.C. § 103(a) for being obvious in light of the ‘065 patent, either alone or based on evidence of inherency.
• That the claims were unpatentable under 35 U.S.C. § 102(b) for being anticipated by U.S. Patent No. 5,690,926 to Hogan, either alone or based on evidence of inherency.
• That the claims were unpatentable under 35 U.S.C. § 103(a) for being obvious in light of the ‘926 patent, either alone or based on evidence of inherency.
• That the claims were unpatentable under 35 U.S.C. § 103(a) for being obvious in light of Robertson ’83 reference, the Robertson ’87 reference, the ‘065 patent, and the ‘926 patent.

However, in Monday’s decision, the Examiner withdrew all these grounds of rejection, finding that the claims were patentable over the combinations of the cited references and under 35 U.S.C. §§ 102 and 103. The Examiner did not merely withdraw these rejections, however, but rather set forth the basis for these determinations for all of the art and all of the arguments raised by the requestor. Specifically, the Examiner made these determinations:

U.S. Patent No. 5,166,056 to Williams does not anticipate the ‘913 patent claims; the Williams patent disclosed only mouse ES cells and did not inherently enable the human ES cells claimed in the ‘913 patent. Moreover, any implied teaching with regard to human ES cells was contradicted by a later paper (Cherny, 1994, Reprod. Fert. Develop. 6: 569-75; Williams co-authored), stating that isolation of human pluripotent ES cells had "remained elusive." Moreover, the Examiner considered the "precise impetus" for Cherny, 1994 was to find alternative methods for producing ES cells from non-mouse species, because the methods used for mouse ES cells had not been "applicable to other domestic animals." Indeed, the Examiner agreed with WARF’s position that Cherny, 1994 contradicted any interpretation that the Williams patent enabled human ES cell preparation. Finally, the Examiner believed that undue experimentation would be required to practice the methods of the Williams patent to produce human ES cells, since there could be no reasonable expectation of success in view of all of the evidence of record.

This belief was supported by evidence from the art, specifically the Gardener and Brook reference (1997, Proc. Natl. Acad. Sci. U.S.A. 94: 5709-12) and the Brook et al. reference (2003, Diabetes 52: 205-08), of the failure of others to produce human ES cells using prior art methods such as those set forth in the Williams patent. The Examiner’s undue experimentation determination was also supported by the Iannacone et al. (1994, Develop. Biol. 163: 288-92) and Ouhibi et al. (1995, Molec. Reprod. Devel. 40: 311-24) references, showing the unpredictability of producing rat ES cells. On the other hand, Doetschman (1988, Develop. Biol. 127: 224-27) isolated hamster ES cells, but Piedrahita (1990, Theriogenology 34: 879-901) failed to isolate ES cells from pigs or sheep, and while unable to determine whether Talbot (1995, Molec. Reprod. & Develop. 42: 35-52) isolated bovine ES cells, the evidence supported the Examiner’s position that the art evidence showed that ES cells were sufficiently unpredictable to amount to undue experimentation absent evidence that ES cells from a particular species had in fact been made.

The most directly applicable reference to the human ES cells of the ‘913 patent was the Bongso reference (1994, Human Reprod. 9: 2010-17) (see "WARF Responds to the Patent Office on Its Re-examined Stem Cell Patents"). However, although the Examiner believed that Bongso may have in fact isolated human ES cells, he was unable to maintain them in culture as recited in the claims.

With regard to obviousness under 35 U.S.C. § 103(a), the Examiner determined that the Williams patent did not support a prima facie obviousness determination, expressly considering the matter under the Supreme Court’s recent KSR Int’l Co. v Teleflex Inc. decision. Specifically, the Examiner determined that the art failed to provide a reasonable expectation of success in achieving the claimed invention, in view of the previously-determined unpredictability in producing ES cells from a variety of mammalian species (including human). The Examiner also determined that evidence of "public acclaim" submitted by WARF would be properly considered as one of the "secondary indicia" of non-obviousness if WARF had established the source of the acclaim as being from those of at least ordinary skill in the art. Since the Examiner concluded that the evidence did not support a prima facie obviousness determination, he did not need to consider the secondary indicia in this case.

Importantly, the Examiner also determined that the declaration evidence submitted by the third party requestor to the effect that Dr. Thomson succeeded in isolating human ES cells where others failed merely due to access to resources (human embryos) and funding others did not have, was merely hindsight reasoning and thus impermissible for consideration in an obviousness determination. The Examiner also noted for the record that at least two of the declarants were not disinterested parties.

Turning to the Hogan patent, the Examiner determined that the EG cells disclosed by Hogan are distinct from the ES cells claimed in the ‘913 patent, and thus that the Hogan patent neither anticipates nor renders obvious the claims of the ‘913 patent. The Examiner’s conclusions were based on comparisons between characteristic properties of the two cell types, including the presence or absence of certain cell surface markers (such as SSEA-1).

Finally, the Examiner considered whether the combination of the ‘065 patent and the ‘926 patent, in view of the Robertson ’83 reference or the Robertson ’87 reference rendered obvious the invention claimed in the ‘913 patent. He found that while the two Robertson references disclosing mouse ES cells provided strong motivation in the art to produce human ES cells, the unpredictability in the art noted above made the claimed invention non-obvious. The Examiner came to the same conclusion with regard to the combination of the ‘065 patent and the ‘926 patent with the Piedrahita 1990 reference discussed above. The Examiner came to the same conclusions when considering the obviousness question in view of the teachings of all these references combined.

The Patent Office decision issued Monday was not a Notice of Allowance or other final determination. Rather, it was a (non-final) Action Closing Prosecution. According to the paper itself, no appeal could be taken from this Action; the patentee has one month to file a "submission," and if one is filed the Third Party Requester has the right to file responsive comments within 30 days. Thereafter, the Office will issue a Right of Appeal Notice pursuant to 37 C.F.R. § 1.953(a), giving the parties one month to file an appeal to the Board of Patent Appeals and Interferences.

One final note: the patentee submitted amendments to the claims that the Examiner states are not necessary for patentability but that "provide further clarity to the claims." Presumably, a re-examination certificate will include the amendments to the claims, which are as follows:

1. A replicating in vitro cell culture of pluripotent human embryonic stem cells derived from a pre-implantation embryo, the culture comprising cells which (i) [[are capable of proliferation]] will proliferate in an undifferentiated state in in vitro culture for over one year without the application of exogenous leukemia inhibitory factor, (ii) maintain a karyotype in which the chromosomes are euploid through prolonged culture, (iii) maintain the potential to differentiate to derivatives of endoderm, mesoderm, and ectoderm tissues throughout the culture, and (iv) are inhibited from differentiation when cultured on a fibroblast feeder layer.

2. The in vitro cell culture [[preparation]] of claim 1, wherein the stem cells will spontaneously differentiate to trophoblast and produce chorionic gonadotropin when cultured to high density.

3. The in vitro cell culture [[preparation]] of claim 1 wherein the cells are negative for the SSEA-1 marker, positive for the SSEA-4 marker, and express alkaline phosphatase.

Two ex parte re-examinations (35 U.S.C. § 302-307) remain: Control No. 90/008102 for U.S. Patent No. 5,843,780 (claiming primate embryonic stem (pES) cells) and Control No. 90/008139 for U.S. Patent No. 6,200,806 (claiming human embryonic stem cell (hES) cells). Since the progress of these re-examinations have paralleled the inter partes re-examination, and in view of the "special dispatch" provisions of the re-examination rules, we should expect a decision in these re-examinations shortly.

For information regarding this and other related topics, please see:

• "WARF Licenses Stem Cell Patent Portfolio to BioTime," January 23, 2008
• "It’s Time to Stop the Hypocrisy over Stem Cell Patents – Part III," July 4, 2007
• "WARF Responds to the Patent Office on Its Re-examined Stem Cell Patents," June 26, 2007
• "It’s Time to Stop the Hypocrisy over Stem Cell Patents – Part I I," April 26, 2007
• "It’s Time to Stop the Hypocrisy over Stem Cell Patents – Part I," April 17, 2007
• "WARF Stem Cell Patent Claims Rejected in Re-examination," April 3, 2007
House Subcommittee Holds USPTO Oversight Hearing

February 27, 2008

By Donald Zuhn —

On Wednesday, the House Subcommittee on Courts, the Internet, and Intellectual Property held an oversight hearing on the U.S. Patent and Trademark Office. The Subcommittee heard statements from Jon Dudas, the Undersecretary of Commerce for Intellectual Property and Director of U.S. Patent and Trademark Office; Robin Nazzaro, the Director of National Resources and Environment for the U.S. General Accountability Office; Robert Budens, the President of the Patent Office Professional Association (POPA); and Alan Kasper, the First Vice President of the American Intellectual Property Law Association (AIPLA) and a partner with Sughrue, Mion, PLLC. Copies of each witness’ statement can be found at the following links: Mr. Dudas’ statement, Ms. Nazzaro’s statement, Mr. Budens’ statement, and Mr. Kasper’s statement. Over the next week, Patent Docs will be reporting on the testimony that was provided to the Subcommittee by each of the above witnesses; today, we begin with Director Dudas’ statement.

With respect to patent initiatives, Director Dudas (at left) divided his discussion into three parts: human capital initiatives (i.e., those affecting the examining corps), administrative and regulatory initiatives, and legislative initiatives. The Director’s testimony also touched on trademark initiatives and the Patent Office’s attempts to strengthen IP rights protection and enforcement worldwide. Before addressing the patent initiatives, the Director noted that the Office had examined more than 362,000 patent applications in 2007, its largest number ever, and had maintained an examination compliance rate of 96.5% for the second year in a row (the examination compliance rate is the percentage of allowed applications that the Office determined had been allowed without examination error). The Director also noted that the patent allowance rate for 2007 was 44%, which constituted a drop of more than 26 points from the allowance rate eight years earlier.

On the topic of human capital initiatives, Director Dudas discussed the Office’s efforts to hire more examiners (the PTO hired 1,215 new examiners in FY 2007 and plans to hire 1,200 more in FY 2008); the Office’s telework programs (the PTO plans to add 500 more examiners to the hoteling program in FY 2008); examiner pay; examiner attrition (the PTO’s 8.5% attrition rate is lower than the 11.2% rate for all federal workers, and interestingly, the attrition rate for examiners with less than three years of experience is almost four times higher than that for examiners with over three years of experience, i.e., 15.5% versus 3.95%); examiner training, certification, and recertification; and the Office’s review of the examination process (applicant and practitioner input in FY 2007 indicated that final rejection practice, Request for Continued Examination (RCE) practice, search quality, and restriction practice are in need of review).

Addressing the subject of administrative and regulatory initiatives, Director Dudas stated that the Office "believes that improvements in patent quality are dependent, to a significant degree, on providing examiners access to more and better-focused information relevant to their decision making," and thus had "promulgated and proposed, and will develop and propose, regulations and administrative changes governing submission and examination of patent applications that will enable our examiners to make more efficient and informed patentability determinations." The Director then discussed a number of these regulations and administrative changes, including accelerated examination, the peer review pilot program, the new Markush rules package, the new Information Disclosure Statement (IDS) rules package, electronic filing and processing improvements (electronic filing of patent applications rose from 2% in FY 2006 to 49.3% in FY 2007), pre-appeal conferences, pre-first Office action and first action examiner interviews, and work-sharing programs with foreign patent offices.

Noting that "’multi-invention alternative’ claims are especially prevalent in the pharmaceutical, chemical, and biotechnology fields," Director Dudas contended that the new Markush rules package "would permit the examiner to focus examination to a single invention [and] encourage applicants to identify, with more specificity, the claimed invention to be examined, thus promoting examination quality." In defending the new IDS rules package, the Director was quick to indict the practices of applicants and practitioners, stating that:

The USPTO has observed that applicants sometimes provide information in a way that hinders, rather than helps, timely and accurate examination. For example, some applicants send a very large number of documents to the examiner, without identifying why they have been submitted, thus tending to obscure the most relevant information. Additionally, some applicants send very long documents without pointing out what part of the document makes it relevant to the claimed invention. Sometimes applicants delay sending key information to the examiner. These practices make it extremely difficult for the patent examiner to find and properly consider the most relevant information in the limited time available for examination of an application.

To those who might criticize the new IDS rules package, the Director explained that under the proposed rules, applicants could still submit as many documents as they choose or very long documents, provided that they satisfied "more stringent requirements" for doing so. The Director concluded his discussion of the Office’s administrative initiatives by noting that the PTO was "looking at a wide variety of alternative examination procedures including those that can be implemented under existing authorities as well as those requiring statutory changes."

With respect to legislative initiatives, Director Dudas discussed patent reform provisions concerning Applicant Quality Submissions (AQS), public quality submissions, and post-grant review. The Director reiterated that the Office "fully endorses the proposed AQS legislative language in the Senate bill, which is consistent with language originally recommended by the Office," explaining that patent applicants have "the most knowledge, the most opportunity, and the most to gain by providing the USPTO with the best possible information" about their inventions. Offsetting (somewhat) his earlier criticism of applicant and practitioner practices with respect to the submission of references, the Director conceded that "[p]olicymakers would also need to consider how the current doctrine of inequitable conduct may discourage applicants from fully and fairly sharing relevant information with the USPTO," and noted that the Office was working with Congress on language that "would encourage applicants to share more information with the Office." On the topic of post-grant review, the Director stated that the PTO supported a first window of 12 months within which any person could seek to cancel as unpatentable any claim of a patent, and a second window of 6 months after a petitioner receives notice from a patent holder alleging infringement and is able to show substantial economic impact.
Finally, Some Good News for Genentech on Avastin®

February 26, 2008

By Kevin E. Noonan —

It has been a difficult year for Genentech with regard to its blockbuster anticancer drug, Avastin® (bevacizumab). For much of the year, the company was embroiled in a dispute with the ophthalmological community over its decision (now altered) to limit sale of Avastin® for reformulation in treating age-related macular degeneration (AMD) in favor of Lucentis®, a related (and much more expensive) formulation of a Fab fragment of the same monoclonal antibody drug but having the advantage of FDA approval for AMD treatment (see links below). Then, just last December, the FDA’s Oncology Drug Advisory Committee voted 5-4 to recommend Avastin® not be approved for treating metastatic breast cancer. The basis for the decision was the absence of a clinical trial of 722 women with metastatic breast cancer, where patients receiving a combination of Avastin® and paclitaxel showed lack of tumor growth for 11.8 months, compared with 5.8 months in patients receiving paclitaxel alone. However, there was no improvement in overall survival (26.5 months versus 24.8 months), and patients receiving Avastin® suffered significant side effects, including high blood pressure, blood clots, heart problems, bowel perforation, and evidence of kidney damage. These results were in contrast with results obtained for Avastin® treatment for lung and colon cancer, where significant overall survival times were improved. They were, however, consistent with an earlier study showing no improved survival times for breast cancer patients treated with the combination of Avastin® and another anticancer drug, capecitabine.

On Friday, the FDA took the unusual step of rejecting the Advisory Panel’s recommendation and approving Avastin® for breast cancer treatment in combination with other anticancer drugs like paclitaxel. Moreover, it granted accelerated approval to this indication of the drug, which is intended "to make promising products for life-threatening diseases available on the market on the basis of preliminary evidence prior to formal demonstration of patient benefit," according to the FDA’s website. Approval is important, as it is estimated to increase Genentech’s already healthy Avastin® sales figures ($2.3 billion in 2007) by almost half a million dollars per year. FDA approval triggers both insurance reimbursement for the treatment and a commitment from Genentech that the cost of treatment will be capped at $55,000 per year (it can cost as much as $100,000 per year without the cap). It is also expected to increase the number of metastatic breast cancer patients getting Avastin® combination therapy from the approximately 9,500 patients currently getting "off-label" treatment.

The decision raises questions of how the FDA will address approval standards for late-stage cancer treatments. According to Dr. Kay Dickerson of the Center for Clinical Trials at Johns Hopkins University, "[i]f FDA sets a precedent of approving a drug based on progression free survival, people are afraid they may stop looking at survival as the most important endpoint." The decision also suggests an acceptance at the FDA of principles advocated by academic critics (and supporters) of the FDA, such as Professor Richard Epstein at the University of Chicago Law School (see "Overdose: How Excessive Government Regulation Stifles Pharmaceutical Innovation"), that the FDA should permit patients to make the judgment of whether to use drugs like Avastin® for terminal diseases. However, those espousing such "free market" solutions neglect to consider whether decisions like the FDA’s approval of Avastin® represents an abdication of the agency’s responsibility to make scientifically-reasoned, dispassionate assessments of drug efficacy for individuals in the throes of deadly diseases, whose capacity for dispassion may be compromised. While certainly the case that the drug can give patients hope (a sentiment expressed by Margaret C. Kirk, Executive Director of the Y-ME National Breast Cancer Organization), whether this is enough to determine approval as a consistent policy is an important question the FDA has yet to adequately address.

For additional information regarding this and other related topics, please see:

• "Compromise Resolves Avastin® Dispute," December 26, 2007
• "Genentech Beset with Avastin® Woes," December 6, 2007
• "Age-related Macular Degeneration Patients Get a (Limited) Reprieve," November 7, 2007
• "Genentech Acts to Halt Off-label Use of Avastin® for Age-related Macular Degeneration," October 21, 2007
• "Genentech CEO Defends Differential Cost for Avastin®/Lucentis® Treatment of Macular Degeneration," June 6, 2007
• "Retinal Specialist on the Avastin®/Lucentis® Controversy," February 23, 2007
• "Lower Doses of Genentech’s Avastin® Effective in Treating Lung Cancer," February 23, 2007
Sigma-Aldrich Licenses Apoptosis Marker

February 26, 2008

By Jason Derry —

Sigma-Aldrich Co. has announced a licensing deal with NeuroSurvival Technologies Ltd. by which Sigma-Aldrich will be allowed to market and manufacture a marker that can detect apoptosis in vitro and in vivo. The marker, commercially known as Apo-TRACE, is one of a number of small molecules, referred to collectively as ApoSense™, that NeuroSurvival has developed to detect apoptotic cells in vivo. An overview of NeuroSurvival’s ApoSense™ technology is available here. The markers can be used for molecular imaging in the areas of disease staging/diagnosis, treatment monitoring, and drug development.

ApoSense™ Positron Emission Tomography (PET) scans can be viewed here.

Jason Derry, Ph.D., who graduated with honors from DePaul University
College of Law, is a molecular biologist and founding author of Patent Docs.
As It Turns Out, It Doesn’t Have to Be a Rose to Smell as Sweet

February 25, 2008

By Kevin E. Noonan —

Insidious (adj.): operating or proceeding in an inconspicuous or seemingly harmless way but actually with grave effect.

On Saturday, The New York Times published an article analogizing two industries most readers would not have thought to be similar: the perfume industry and innovator pharmaceutical companies (see "Ahh, the Seductive Fragrance of Molecules under Patent"). But the similarities are manifold, and upon reflection are not that surprising.

Like the pharmaceutical industry, perfumeries are constantly in need of new molecules, not to treat diseases of course but to provide the source material for new fragrances. For example, the article cites Kate Greene, vice president for marketing at Swiss scent maker Givaudan, as saying the company makes more than 2,000 new scent molecules every year, but develops only 3 or 4 of them as commercial products. Development costs are high: although Givaudan has annual profits of 2.9 billion Swiss francs, it also invests almost 400 million francs in research each year and employs more than 50 scientists in these efforts. Similar efforts are reported in the article for Japanese scent company Takasago International Corporation; Symrise of Holzminden, Germany; and International Flavors and Fragrances of New York, who collectively spend "billions" in research.

The return on investment is high, with individual scents (used as components for popular perfumes and other fragrances) so dear, their producers decline to specify their cost (other than saying they were "not cheap). These new scent molecules provide the raw material for the up to 600 new fragrances introduced each year. They also have advantages over naturally-occurring scents, such as lacking allergenicity present in natural products such as rose ketones, the amount of which is restricted due to their propensity to provoke allergic reactions. Other advantages include the capacity to cling to fabrics, to be used in scented laundry products and soaps, while at the same time being more potent so that less scent must be used (and less water used to wash the scent away).

Importantly, there are also ecological advantages: for example, the article cites the price of natural sandalwood as reaching $1,700 per kilogram, due to severe over-foresting of Indian sandalwood that forced the Indian government to ban further harvesting. Additionally, using synthetic rather than naturally-occurring scents avoids the ancillary economic and ecological costs of fertilizers, soil erosion, and diverting cropland to non-agricultural uses.

Some of the most expensive of the scents, described as "captives" in the industry, are those that are under patent, the most potent analogy made by the article to the pharmaceutical industry. In addition to the analogies noted above to the high development costs and low probability of success, the article also notes the importance of toxicology and the effects of the scope of available patent protection in different countries (while getting the current extent of U.S. patent term wrong, citing a figure not used for the past thirteen years).

But the analogies to patenting and its importance to the industry are where an otherwise informative article goes a little wrong. Maybe it’s because the Times published it, or maybe it’s the title ("Ahh, the Seductive Fragrance of Molecules under Patent") (something that could be the product of a copy editor well aware of the Times patent animus). Whatever the reason, rather than being enlightening, the patent angle seems gratuitous. The antiparallels to pharmaceuticals are never mentioned: the much higher regulatory costs and barriers for drugs, the factors other than toxicity that can make even fewer potential drug leads suitable for commercialization, and of course the unstated difference between "luxury" items like perfumes and life-saving drugs. And the overall effect is insidious: another Times article where patents are not described as helping companies protect hard-earned investment but rather just make things cost too much. The unspoken assumptions have substantive consequences: in discussing Takasago’s patent strategy for it synthetic must product, l-muscone (the company patented the synthetic methods rather than the scent itself), the effect, that these methods will be dedicated to the public when Takasago’s patents expire goes unmentioned. It seems a shame that such important considerations are left to innuendo or discussed obliquely, even by the Times. You might even say it stinks.

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