Patent Docs

Yes, It IS Time (Finally) to Stop the Hypocrisy over Human Stem Cell Patents

March 12, 2008

By Kevin E. Noonan —

The two remaining ex parte re-examinations (35 U.S.C. § 302-307) of Wisconsin Alumni Research Foundation (WARF) stem cell patents — 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) — have been decided, and the U.S. Patent and Trademark Office has determined that the claims of these patents are patentable, after all. These decisions are a stunning victory for WARF, and a crushing defeat for the Public Patent Foundation (PUBPAT), headed by Dan Ravicher, and the Foundation for Taxpayer and Consumer Rights (FTCR), a California taxpayer group (which recently became ConsumerWatchdog.org).

Unlike the 85-page decision announcing the patentability of WARF’s U.S. Patent No. 7,029,913 in an inter partes re-examination (35 U.S.C. § 311-318) proceeding (see "(Finally) It May Be Time to Stop the Hypocrisy over Stem Cell Patents"), the Office dispensed with these two challenges much more parsimoniously. In re-examination of the ‘780 patent, the original grounds of rejection asserted by the Examiner were as follows:

• That claims 1-11 were unpatentable under 35 U.S.C. § 102(b) for being anticipated by U.S. Patent No. 5,166,065 to Williams.
• That claims 1-8 and 11 were unpatentable under 35 U.S.C. § 103(a) for being obvious in light of the ‘065 patent.
• That claims 1-8 were unpatentable under 35 U.S.C. § 102(b) for being anticipated by U.S. Patent No. 5,690,926 to Hogan.
• That claims 1-8 were unpatentable under 35 U.S.C. § 103(a) for being obvious in light of the ‘926 patent.
• That claim 11 was unpatentable under 35 U.S.C. § 102(b) for being anticipated by Bongso et al., 1994, Hum. Reprod. 9: 2110-17 (see "WARF Responds to the Patent Office on Its Re-examined Stem Cell Patents").
• That claim 11 was unpatentable under 35 U.S.C. § 103(a) for being obvious in light of the Bongso reference.
• That claims 1-11 were unpatentable under 35 U.S.C. § 103(a) for being obvious in light of Robertson ’83 (Cold Spring Harbor 10: 647-63), the Robertson ’87 reference (Teratocarcinomas and Embryonic Stem Cells: A Practical Approach, IRL Press), or Piedrahita et al., 1990, Theriogenology 34: 879-901, taken alone or in combination with the ‘065 and ‘926 patents.

In the communication mailed on Tuesday, all these grounds of rejection were withdrawn and the claims as amended by the patentee were deemed patentable. Amended claims 1, 3, 9 and 11 and added new claims 12-14 read as follows:

1. A purified preparation of pluripotent primate embryonic stem cells derived from preimplantation embryos wherein the stem cells (i) will proliferate in an in vitro culture for over one year in an undifferentiated state, (ii) maintain a karyotype in which all the chromosomes characteristic of the primate species are present and not noticeably altered through prolonged culture, (iii) maintain the potential to differentiate into derivatives of endoderm, mesoderm, and ectoderm tissues throughout the culture, and (iv) will not differentiate when cultured on a fibroblast feeder layer.

3. A purified preparation of primate embryonic stem cell line wherein the cells of the cell line are negative for the SSEA-1 marker, positive for the SSEA-3 marker, positive for the SSEA-4 marker, express alkaline phosphatase activity, are pluripotent, and have karyotypes which includes the presence of all of the chromosomes characteristic of the primate species and in which none of the chromosomes are noticeably altered.

9. A method of isolating a pluripotent primate embryonic stem cell line, the method comprising the steps of:
(a) isolating a primate blastocyst;
(b) isolating cells from the inner cell mass of the blastocyst of (a);
(c) plating the inner cell mass cells on embryonic fibroblasts, wherein inner cell mass-derived cells masses are formed;
(d) dissociating the mass into dissociated cells;
(e) replating the dissociated cells on embryonic feeder cells;
(f) selecting colonies with compact morphologies and cells with high nucleus to cytoplasm ratios and prominent nucleoli; and
(g) culturing the cells of the selected colonies to produce an isolated pluripotent primate embryonic stem cell line that is capable of proliferating as undifferentiated cells for over one year.

11. A cell line that is capable of proliferation for over one year developed by the method of claim 9.

12. A method of isolating a pluripotent primate embryonic stem cell line, the method comprising the steps of:
(a) isolating a primate blastocyst;
(b) isolating cells from the inner cell mass of the blastocyst of (a);
(c) plating the inner cell mass cells on embryonic fibroblasts, wherein inner cell mass-derived cells masses are formed;
(d) dissociating the mass into dissociated cells;
(e) replating the dissociated cells on embryonic feeder cells;
(f) selecting colonies with compact morphologies that are flatter than mouse embryonic stem cell colonies, wherein the cells with high nucleus to cytoplasm ratios and prominent nucleoli; and
(g) culturing the cells of the selected colonies to produce an isolated pluripotent primate embryonic stem cell line that is capable of proliferating as undifferentiated cells for over one year.

13. A method as claimed in claim 12, further comprising maintaining the isolated cells on a fibroblast feeder layer to prevent differentiation.

14. A cell line that is capable of proliferation for over one year as undifferentiated cells developed by the method of claim 12.

The Examiner made these determinations in the Statement of Reasons for Patentability:

U.S. Patent No. 5,166,056 to Williams does not anticipate the ‘780 patent claims because the Williams patent disclosed only mouse ES cells and did not inherently enable the hES cells claimed in the ‘780 patent. Moreover, any implied teaching with regard to hES cells was contradicted by a later paper (Cherny and Williams, 1994, Reprod. Fert. Develop. 6: 569-75), stating that the methods of isolating mouse embryonic stem cells "would not extend" to methods for isolating human pluripotent ES cells. The Williams ‘065 patent also did not disclose primate ES cells that differ from mouse ES cells in the expression of markers like SSEA-1, nor do the mouse ES cells differentiate into trophoblast when induced to differentiate. The Williams ‘065 patent was limited to mouse ES cells. Moreover, the Examiner believed that undue experimentation would be required to practice the methods of the Williams patent to produce hES cells, since there could be no reasonable expectation of success in view of all of the evidence of record.

Turning to the ‘926 patent, the Examiner determined that the EG cells disclosed by Hogan are distinct from the ES cells claimed in the ‘780 patent, because: (1) they were derived from post-implantation embryos; (2) the Hogan EG cells are SSEA-1 positive; and (3) the Hogan EG cells do not differentiate into trophoblast when differentiation is induced. The Examiner, therefore, found that the ‘926 patent neither anticipates nor renders obvious the claims of the 780 patent. In addition, the methods used by Hogan would not render obvious the ES cells obtained from pre-implantation embryos. Finally, the Examiner found that the degree of unpredictability in producing hES cells having the properties of the hES cells claimed in the ‘780 patent precluded the reasonable expectation of success required to support an obviousness determination.

The Examiner determined that the Bongso reference (Ariff Bongso at right) did not teach pluripotent embryonic stem cells that proliferate for over one year in an undifferentiated state (noting that the cells produced by Bongso either differentiated into fibroblasts or died after the second culture passage), nor did they exhibit the other characteristic features of the hES cells claimed in the ‘780 patent. Moreover, a Declaration from the ‘780 patent inventor, James Thomson, established that Thomson had invented his ES cells prior to the November 1994 publication date of the Bongso reference.

Finally, the Examiner considered whether the combination of the Robertson ’83 reference, the Robertson ’87 reference, or the Piedrahita reference, either alone or in combination with the ‘065 patent and the ‘926 patent, rendered the ‘780 patent obvious. He found that while the two Robertson references disclosing mouse ES cells taught methods for producing mouse ES cells, the Piedrahita reference failed to isolate ES cells from pigs or sheep and showed that the methods used to produce mouse ES cells were not applicable to other mammals and indeed, taught away from applying techniques used in mice in other mammals. The combination thus did not render obvious the claims of the ‘780 patent. The Examiner came to the same conclusion with regard to the combination of these references with the teachings of the ‘065 patent and the ‘926 patent.

In re-examination of the ‘806 patent, the Robertson ’83, Robertson ’87, Piedrahita, and Bongso references, and Williams ‘065 and Hogan ‘926 patents were applied to the claims, as well as U.S. Patent 5,453,357 to Hogan; Behrouz et al., 2005 (Current Opinion in Biotechnology 16: 530-535), and Cruz et al., 1991 (Current Communications 4: 147-204). The Notice expressly defined the terms "stem cells," "embryonic stem cells," "pluripotent," and "true ES cells."

With respect to the ‘806 patent, the Examiner withdrew the following grounds of rejection:

• That claims 1-8 and 11 were unpatentable under 35 U.S.C. § 102(e) for being anticipated by the ‘926 or ‘357 patents alone, or as further evidenced by the ‘806 patent disclosure demonstrating inherency.
• That claim 11 was unpatentable under 35 U.S.C. § 102(a) for being anticipated by the Bongso reference.
• That claim 11 was unpatentable under 35 U.S.C. § 103(a) for being obvious in light of the Bongso reference.
• That claims 1-11 were unpatentable under 35 U.S.C. § 102(b) for being anticipated by the ‘065 patent.
• That claims 1-11 were unpatentable under 35 U.S.C. § 103(a) for being obvious in light of the ‘065 patent.
• That claims 1-11 were unpatentable under 35 U.S.C. § 103(a) for being obvious in light of the Robertson ’83 reference, Robertson ’87 reference, or Piedrahita reference, taken alone or in combination with the ‘065 and ‘926 patents.

The amended claims of the ‘806 patent read as follows:

1. A purified preparation of pluripotent human embryonic stem cells derived from preimplantation embryos wherein the stem cells (i) will proliferate in an in vitro culture for over one year in an undifferentiated state, (ii) maintain a karyotype in which the chromosomes are euploid and not altered through prolonged culture, (iii) maintain the potential to differentiate into derivatives of endoderm, mesoderm, and ectoderm tissues throughout the culture, and (iv) are inhibited from differentiation when cultured on a fibroblast feeder layer.

3. A purified preparation of primate embryonic stem cell line wherein the cells of the cell line are negative for the SSEA-1 marker, positive for the SSEA-3 marker, positive for the SSEA-4 marker, express alkaline phosphatase activity, are pluripotent, and have euploid karyotypes and in which none of the chromosomes are altered.

9. A method of isolating a pluripotent primate embryonic stem cell line, comprising the steps of:
(a) isolating a human blastocyst;
(b) isolating cells from the inner cell mass of the blastocyst of (a);
(c) plating the inner cell mass cells on embryonic fibroblasts, wherein inner cell mass-derived cells masses are formed;
(d) dissociating the mass into dissociated cells;
(e) replating the dissociated cells on embryonic feeder cells;
(f) selecting colonies with compact morphologies and cells with high nucleus to cytoplasm ratios and prominent nucleoli; and
(g) culturing the cells of the selected colonies the thereby obtain an isolated pluripotent human embryonic stem cell line that is capable of proliferation as undifferentiated cells for over one year.

11. A cell line that is capable of proliferation for over one year developed by the method of claim 9.

12. A method of isolating a pluripotent human embryonic stem cell line, the method comprising the steps of:
(a) isolating a human blastocyst;
(b) isolating cells from the inner cell mass of the blastocyst of (a);
(c) plating the inner cell mass cells on embryonic fibroblasts, wherein inner cell mass-derived cells masses are formed;
(d) dissociating the mass into dissociated cells;
(e) replating the dissociated cells on embryonic feeder cells;
(f) selecting colonies with compact morphologies that are flatter than mouse embryonic stem cell colonies, wherein the cells with high nucleus to cytoplasm ratios and prominent nucleoli; and
(g) culturing the cells of the selected colonies to produce an isolated pluripotent human embryonic stem cell line that is capable of proliferating as undifferentiated cells for over one year.

13. A method as claimed in claim 12, further comprising maintaining the isolated cells on a fibroblast feeder layer to prevent differentiation.

14. A cell line that is capable of proliferation for over one year as undifferentiated cells developed by the method of claim 12.

The Examiner found that neither the Hogan ‘926 nor Hogan ‘357 patents taught hES cells that did not express SSEA-1 on the cell surface, were derived from preimplantation embryos or could be derived from human blastocysts. The inherent expression of SSEA-1 was considered a marker that the hES cells claimed in the ‘806 patent were patentably distinct from Hogan’s EG cells. The Examiner cited the Behrouz reference in support of this distinction. The Examiner also found that the Bongso reference did not anticipate Claim 11, since Bongso’s cells had none of the proliferation properties of the hES cells encompassed by the claims. In addition, a Declaration by the inventor established an earlier date of invention prior to the publication date of the Bongso reference.

Turning to the Williams ‘065 patent, the Examiner found that both the prosecution history of the patent (wherein the Examiner had required Williams to limit the claims from "animal" ES cells to mouse ES cells), and the Cherney-Williams reference showed that the Williams ‘065 patent was not enabling for the hES cells claimed in the ‘806 patent. Finally, the Examiner determined that the combination of the Robertson ’83 reference, Robertson ’87 reference, or Piedrahita reference, taken alone or in combination with the ‘065 and ‘926 patents did not "engender a reasonable expectation of success" in producing the hES cells claimed in the ‘806 patent.

The Examiner also expressly set forth the evidence for and against a prima facie obviousness case originally raised against the ‘806 patent claims. On the side of non-obviousness, the Examiner found that "the prior art of record neither discloses nor contained an enabling suggestion of how to make true hES cells or cell lines without the necessity for undue experimentation." Thus, despite a high level of ordinary skill in the art, "there was no reasonable expectation of successfully isolating true hES cells or cell lines" using methods successful in mice, "given the highly unpredictable nature of the prior art."

The Examiner noted that as of the priority date of the ‘806 application (January 20, 1995), no one had reported isolating a hES cell line, despite the fact that rodent (mouse, hamster, and rat) ES cell lines had been isolated and their properties characterized. The Examiner also noted the unique features of the hES cells claimed in the ‘806 patent: permanent, euploid, embryo-derived cell lines that could differentiate into all three embryonic germ cell layers. The Examiner also cited the combination of the success taught by the Robertson references with regard to mouse ES cells, and the failures described in the Piedrahita reference in attempting to apply these teachings to ES cells from other mammalian species. The Examiner cites the Cruz reference on the differences between ES cells from different mammalian species, which supports the non-obviousness determination. Finally, the Examiner uses the Hogan ‘926 patent as evidence that the art recognized the difficulty in producing hES cells, and thus turned to primordial germ cells (EG cells) as an alternative.

The Examiner also cited the evidence of failure of others and the "wide acclaim" Dr. Thomson received from his peers as objective indicia of non-obviousness.

The evidence supporting the obviousness determination, on the other hand, was principally the declaration submitted by Dr. Jeanne Loring (see "It’s Time to Stop the Hypocrisy over Stem Cell Patents – Part III"). In addition, Professor Loring (at right) testified to conversations with Dr. Hogan and Dr. Iannaccone "regarding putative or actual attempts at obtaining hES cells from blastocysts using the same techniques disclosed in the Robertson references" relating to mouse ES cells. The Examiner opined that "little weight" should be given Dr. Loring’s declaration evidence "since it states opinion on the ultimate legal issue [obviousness] without providing sufficient underlying factual support." The Examiner also gave little weight to the "uncorroborated conversations" Dr. Loring putatively had with other experts, "when considered in light of all the documentary evidence of record."

Balancing the factual evidence, the Examiner concluded that the ‘806 patent claims were not obvious.

These decisions cannot be appealed by the third party requestor, since their active involvement ended when the ex parte re-examination was declared (although they were served with all papers between the Patent and Trademark Office and WARF during the pendency of the re-examination). Since neither PUBPAT nor FTCR are practicing the claimed invention, they have no standing to ask a District Court for a declaratory judgment of invalidity, and such a judgment should only be harder to obtain in view of the results of these re-examinations.

This is good news for WARF and Professor Thomson, who can now get back to his research on making pluripotent stem cells from fibroblasts, a more robust and less ethically and politically controversial procedure. After trumpeting as victories the initial (and expected) Office Action rejections issued by the Patent Office in these re-examinations, perhaps PUBPAT and FTCR will be more prudent and circumspect about the "bad" patents it chooses to attack. After all, they have to be out there, don’t they?

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

• "(Finally) It May Be Time to Stop the Hypocrisy over Stem Cell Patents," February 28, 2008
• "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
You Can’t Fight the USPTO — or Can You?

March 11, 2008

By Donald Zuhn —

As we reported yesterday, the U.S. Patent and Trademark Office published a Notice in the Federal Register on Monday supplementing to its Alternative Claims Notice of Proposed Rule Making from last August. According to the Patent Office, the supplementary Notice was published in response to comments to the first Notice that questioned the impact of the proposed alternative claims rules on small businesses and independent inventors. While the supplementary Notice makes it abundantly clear that the Office believes that the new alternative claims rules "involve rules of agency practice and procedure for which prior notice and an opportunity for public comment are not required pursuant to 5 U.S.C. 553 (or any other law), and thus neither a regulatory flexibility analysis nor a certification under the Regulatory Flexibility Act (5 U.S.C. 601 et seq.) is required under 5 U.S.C. 603," the Patent Office has nevertheless decided to "subject the proposed rules to a regulatory flexibility analysis to provide a further opportunity for comment on the small business impact of the proposed rules."

The Patent Office’s decision to provide an economic impact analysis for the proposed alternative claims rules (notwithstanding the fact that this analysis is being provided at the last minute) may be indication that recent attacks on the economic impact of the Office’s other rules packages are finally having the desired effect. Examples of such challenges include Dr. Richard Belzer’s submission to the Office of Management and Budget (OMB) of additional information regarding the paperwork burdens of the final claims and continuations rules and the final IDS rules, which Dr. Belzer estimated to be between $13 billion and $34 billion per year, and separate OMB submissions made by Dr. Belzer and David Boundy, which provided estimates of between $1.9 billion (Mr. Boundy) and $7.9 billion (Dr. Belzer) for the economic impact of the new IDS rules.

After the Patent Office published its supplementary Notice, we had a chance to discuss strategies for challenging the alternative claims rules with the architects of the campaigns against the claims and continuations rules and IDS rules. For those interested in providing the PTO with comments about the alternative claims rules or their economic impact, or alternatively, writing to the OMB about the economic impact of the alternative claims rules, Dr. Belzer’s and Mr. Boundy’s insights should prove to be invaluable.

Dr. Belzer (at left), who served as a civil service staff economist in the Office of Information and Regulatory Affairs within the OMB, began his discussion by noting that the Patent Office made four key assertions in the Alternative Claims Notice of Proposed Rule Making:

1. The proposed alternative claims rules are "not significant" as defined by Executive Order 12,866, and therefore, the Office "deemed [the rules] to be a trivial administrative matter below the threshold for centralized review by OMB."

2. The proposed alternative claims rules are procedural, and therefore, exempt from the Administrative Procedure Act (APA). Dr. Belzer contends that the Office’s request for comments "was a defensive maneuver just in case the Office was challenged in court."

3. Because the alternative claims rules are exempt from the APA, they are also exempt from the Regulatory Flexibility Act.

4. The alternative claims rules have no associated paperwork burdens (the Paperwork Reduction Act requires agencies to provide public notice and seek comment on paperwork burdens associated with notices of proposed rule making). Dr. Belzer observed that the Patent Office has apparently not changed its position on this point, since the supplementary Notice was silent about paperwork burdens.

With respect to the first point, Dr. Belzer recalls two recent challenges to an agency’s certification that a rules package has "no significant impact on a substantial number of small entities." Patent attorneys are quite familiar with the first — the Tafas/GSK v. Dudas challenge, for which we eagerly await a decision. The other case is AFL-CIO v. Chertoff, which Dr. Belzer describes as involving a final rule establishing a safe harbor for employers trying to comply with the Immigration Control Act after receiving a letter from the Social Security Administration about inconsistencies between SSA records and an employee’s name and social security number. In AFL-CIO, the Department of Homeland Security made a "no significant impact" certification, which a district court found to be improbable prior to issuing an injunction barring implementation of the rule. Dr. Belzer believes that the major difference between Tafas/GSK and AFL-CIO is that in AFL-CIO, the Small Business Administration (SBA) Office of Advocacy weighed in on behalf of the plaintiffs, and in Tafas/GSK, it "rolled over." [UPDATE: For more information regarding the AFL-CIO case, please see "DHS’ ‘No-Match Rule’ Stopped by Preliminary Injunction: The Regulatory Flexibility Act and Illegal Aliens." A copy of the opinion can be found here.]

Dr. Belzer then addressed a few strategies for those who may want to be heard regarding their opposition to the Patent Office’s latest rule making effort:

1. Submit informed comments on the Patent Office’s Regulatory Flexibility Act analysis. According to Dr. Belzer, informed comments must go beyond mere "whining," and instead, take apart the Office’s analysis and put it together "as it should have been done in the first place." Dr. Belzer believes that this was done for the continuation and claims rules, but only after the Office published the final rules in August, rather than at the notice of proposed rule making stage. Unlike with the continuation and claims rules, where "no one in the patent world understood the game," Dr. Belzer thinks that opponents of the alternative claims rules are "much better situated to be effective."

2. Pressure the SBA Office of Advocacy to intervene aggressively against the alternative claims rules.

3. Get the alternative claims rules on the OMB’s radar. Dr. Belzer contends that the OMB is the critical entity for implementation and enforcement of Executive Order 12,866 and the Paperwork Reduction Act. He also notes that the OMB has a significant interest in Regulatory Flexibility Act analyses, even though the SBA Office of Advocacy has more influence with respect to such analyses.

4. Develop and provide the OMB with credible estimates of the paperwork burden of the alternative claims rules. Dr. Belzer points out that the alternative claims rules cannot be legally finalized without a showing of prior compliance with the Paperwork Reduction Act, stating that to the extent someone shows bona fide paperwork burdens, "then PTO is out of compliance with the law and OMB cannot allow it to proceed." Finally, Dr. Belzer notes that the OMB is accepting of anonymity, since the "PTO’s means, motive and opportunity to retaliate are easy to explain and readily convincing" (note: in his previous representations to the OMB, Dr. Belzer did not reveal the identity/identities of his client/clients because he discerned a credible basis for fearing retaliation).

Mr. Boundy (at left), the Vice President of Intellectual Property for Cantor Fitzgerald L.P., wanted to let Patent Docs readers know that Dr. Belzer "is an incredibly valuable (and cost-effective) resource on these intra-executive-branch rulemaking oversight issues," and recommended that anyone interested in writing to the OMB contact him at rbbelzer@post.harvard.edu.

With respect to submitting comments to the Patent Office, Mr. Boundy noted that while the Office’s supplementary Notice concerned the economic impact of the alternative claims rules on small entities, large entities could also submit comments provided that they focused on the economic impact of the rules on small entities. Mr. Boundy also recommended that comments address (a) the estimated burden of the proposed rules in dollars per year, and (b) flaws and omissions in the Patent Office’s assumptions and analyses. He notes that the types of burdens that are cognizable under the Regulatory Flexibility Act include additional paperwork costs, management of additional files and other information because of additional restriction requirements, loss of patent term, loss of asset value for species not pursued, business opportunities foregone, investments not made, companies not formed, companies that go out of business, and additional litigation arising out of double patenting issues.

Mr. Boundy agreed with Dr. Belzer that an effective strategy could be to focus on the fact that the Patent Office advised the OMB that the alternative claims rules were "not significant," which Mr. Boundy argues is a category reserved only for rules that "impose essentially zero burden, present no substantive issues, and are entirely non-controversial." In the supplementary Notice, however, the Patent Office has now taken a somewhat contrary position by arguing that the alternative claims rules will have a more "significant" impact.

For those writing to the OMB, Mr. Boundy advises that letters be addressed to:

The Honorable Susan E. Dudley
Administrator
Office of Information and Regulatory Affairs
Office of Management and Budget
Washington, DC 20503

[UPDATE: Dr. Belzer recommends that submissions be faxed or e-mailed to Ms. Dudley, rather than sent by regular mail, since the White House puts regular mail through intensive – and, therefore, time consuming – screens for anthrax.]

He also suggests that interested parties refer to exemplary letters that can be found here and here. More importantly, Mr. Boundy contends that writing the OMB is "an effective route to pursue," noting that he has received "some back channel feedback" that the IDS rule — originally scheduled to be published by the end of 2007 — is now "on indefinite hold" pending resolution of several similar challenges and the Tafas/GSK v. Dudas case. He also believes that the Patent Office’s refusal to reply to several pending challenges (some might say stalling tactics) is further evidence of the effectiveness of such a strategy.
Thailand Continues Its Compulsory Licensing Practices

March 11, 2008

By Kevin E. Noonan —

Any hopes that Thailand would amend or overrule its policy of ignoring drug patent rights were dashed when the Thai government announced that it intended to maintain its extension of its compulsory licensing policy to four anti-cancer drugs: Novartis' Imatinib® and Letrozole®, Sanofi-Aventis' Docetaxel®, and Roche's Erlotinib®. The motivation is clear — these compulsory licenses are estimated to save Thailand more than 3 billion baht ($100 million) over the next five years.

These actions are consistent with previous compulsory licenses granted on anti-AIDS drugs, including Abbott's Aluvia®, a heat-stable formulation of Kaletra® (see "Pharma Sanity Lacks Global Reach"), as well as Novartis' anti-leukemia drug Glivec®; ironically, the compulsory license on Glivec® was cancelled when Novartis agreed to supply the drug free to Thai patients. These activities have been met with strong condemnation from the U.S., which placed Thailand on its "priority watch list" in its Special Section 301 Report last May (see "Worldwide Drug Pricing Regime in Chaos"), and the European Union, where Trade Commissioner Peter Mandelson demanded Thailand stop its compulsory licensing program (see "EU Trade Commissioner Sends Warning Letter to Thailand").

All this is occurring against a backdrop of political turmoil in the Thailand government's regulatory ranks. Last week, Chatree Banchuen, only recently appointed the head of Thailand's Food and Drug Administration, resigned over the issue. His predecessor, Siriwat Thiptharadon, was the architect of the latest scheme to grant compulsory licenses on the four drugs, and has charged that his demotion to an inactive government post was caused by his anti-patent stance. The new Thai Public Health Minister, Chaiya Sasomsup, affirmed that compulsory licenses would be maintained unless Thailand was successful in negotiating an "affordable price" for the drugs. And these actions seems to validate comments from the Thai Public Health Minister, Mongkol Na Songkhla, that indicate that Thailand will further expand this category for all "essential" drugs needed to support the government's universal health care plan.

The opposition (such as it is) within the Thai government is based in part on apprehension that the U.S. or EU would impose trade sanctions on Thailand in response to compulsory licensing. However, the provisions of the Doha Declaration have made the success (and legality) of such sanctions less likely.

Of course, some in the Thai government say the drug companies only have themselves to blame. Suwit Wibulpolprasert (at left), a senior adviser on disease control at the Thai Ministry of Public Health, alleges that Western drug companies refused to negotiate with the Thai government until they were threatened with compulsory licenses.

The abiding irony is that the very international agreements intended to increase intellectual property rights in countries like Thailand have instead provided such countries with all the promised protections for their own industries while permitting these countries to violate patent protection for a wide range of pharmaceuticals. Prudence suggests that Western drug companies and their governments come up with a strategy that will accommodate the companies' legitimate interest in protecting their intellectual property and investment in these drugs while at the same time recognizing the political and economic pressures on countries like Thailand to take advantage of the provisions of GATT and the WTO that make these drugs affordable. That has not happened yet, and with the tide turning towards more countries using these treaty provisions (notably, the Doha Declaration) to grant compulsory licenses and parallel importing for more drugs for treating more diseases, it can't come soon enough.

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

• "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
Dealing with the EPO’s New Excess Claims Fees

March 11, 2008

By Brad Crawford —

As we previously reported, on December 14, 2007, the Administrative Council of the European Patent Organization increased the amounts of various fees that patent applicants are required to pay. The Council’s decisions can be found here and here. We summarize the changes to the claim fees below, and provide some comments regarding prosecution strategy.

Claim fees are being increased in a two step process. In the first step, which applies to all claim fees paid on or after April 1, 2008, the claim fee for the 16th and each subsequent claim is being increased to 200 EUR. Under current practice, each additional claim after the 10th is charged a fee of 45 EUR. Clearly, this is a significant increase.

All U.S. applicants filing in Europe must be aware of this, as under U.S. practice, the applicant is entitled to 20 claims. Merely filing a U.S. application containing 20 claims in Europe will cost the U.S. applicant an extra 1,000 EUR in excess claim fees. Thus, it may be prudent to reduce the number of claims by either canceling some claims or by making some of them multiply dependent.

In the second step, which applies to all European patent applications filed on or after April 1, 2009, as well as to International applications that enter the European regional phase on or after April 1, 2009, the claim fees will be changed as follows:

Claims 16 to 50 will still be charged 200 EUR each, but claim 51 (and all subsequent claims) will be charged a claim fee of 500 EUR per claim. This fee increase, while applying to relatively few applications, is quite draconian, and efforts should obviously be made to avoid it.

One way to avoid paying these higher claim fees is to pay the fees before the fee increases take effect. Quite simply, if you recently filed a European regional phase application, you may want to have your European associate pay the claim fees now, even though the European Patent Office has not issued an invitation to pay the additional claim fees and/or submit amended claims.

Another strategy is to utilize the provisions of Rule 110, which allows an applicant to file an amended claim set, after entry into the European regional phase. Rule 110 reads as follows:

Rule 110

Claims incurring fees
Consequence of non-payment

(1) If the application documents on which the European grant procedure is to be based comprise more than ten claims, a claims fee shall be payable for the eleventh and each subsequent claim within the period provided for in Rule 107, paragraph 1.

(2) Any claims fees not paid in due time may still be validly paid within a non-extendable period of grace of one month as from notification of a communication pointing out the failure to pay. If within this period amended claims are filed, the claims fees due shall be computed on the basis of such amended claims.

(3) Any claims fees paid within the period provided for in paragraph 1 and which are in excess of those due under paragraph 2, second sentence, shall be refunded.

(4) Where a claims fee is not paid in due time, the claim concerned shall be deemed to be abandoned.

In Europe, after an application is filed, the European Patent Office will issue a notice giving the applicant a non-extendable, one month grace period for filing an amended claim set and for paying any excess claim fees that were not previously paid (see (2) above). Thus, it is possible to reduce the number of claims to be examined, which decreases the claim fees that have to be paid.

Further, if excess claim fees were paid when the basic national fee was paid, it is still possible to submit an amended claim set containing fewer claims (again, within the non-extendable, one-month grace period) and to obtain a refund on the excess claim fees that were paid (see (3) above). A related strategy is to file multiple applications in Europe, each directed towards a different invention and each having no more claims than are necessary. This necessitates paying a new filing fee and will incur additional prosecution related expenses, but if the original application contains significantly more than 50 claims, this option should be considered.
Pfizer, Inc. v. Teva Pharmaceuticals USA, Inc. (Fed. Cir. 2008)

March 10, 2008

By Kevin E. Noonan —

On Friday, the Court of Appeals for the Federal Circuit handed Pfizer a mixed decision on defendant Teva’s appeal of a District Court judgment that Teva was liable for infringing a trio of Pfizer patents (U.S. Patent Nos. 5,466,823; 5,563,165; and 5,760,068) relating to the pain medication Celebrex® (celocoxib). While keeping Teva’s generic celocoxib off the market for now, the Federal Circuit’s ruling advances the date when the generic version of Celebrex® will become available by about 12 months.

Pfizer initiated its lawsuit upon notification by Teva of its Paragraph IV certification filed in Teva’s Abbreviated New Drug Application (ANDA) with the FDA. Although Pfizer asserted a number of claims against Teva, the claims relevant to the issues on appeal were claim 9 of the ‘823 patent:

Compound of claim 8 where the compound is [celocoxib], or a pharmaceutically-acceptable salt thereof.

Claim 17 (dependent on claim 15) of the ‘165 patent:

A pharmaceutical composition comprising a therapeutically-effective amount of a compound and a pharmaceutically-acceptable carrier or diluent, said compound selected from a family of compounds . . . where the compound is [celocoxib], or a pharmaceutically-acceptable salt thereof.

And claim 4 (dependent on claim 1) of the ‘068 patent:

A method of treating inflammation or an inflammation-associated disorder in a subject, said method comprising administering to the subject having or susceptible to such inflammation or inflammation-associated disorder, a therapeutically-effective amount of a compound . . . where the compound is [celocoxib], or a pharmaceutically-acceptable salt thereof.

(Where "celocoxib" is 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-
yl]benzenesulfonamide.)

The District Court found the asserted claims infringed, the claims of the ‘068 patent not invalid for obviousness-type double patenting, claim 9 of the ‘823 patent and claim 17 of the ‘165 patent not invalid for violation of the best mode, and the asserted claims not unenforceable due to alleged inequitable conduct.

The Federal Circuit, in a unanimous opinion by Judge Dyk (joined by Chief Judge Michel and District Judge Matthew Kennelly of the Northern District of Illinois, sitting by designation) reversed the District Court’s determination that the claims of the ‘068 patent were not invalid for obviousness-type double patenting but affirmed Teva’s failure to carry its burden of a best mode violation or inequitable conduct on the other asserted patents. The basis for the Federal Circuit’s decision that the ‘068 patent was invalid for obviousness-type double patenting was that the designation of this patent as a "continuation-in-part" was not merely semantic but had substantive repercussions regarding whether the ‘068 claims were entitled to the "safe harbor" provisions of 35 U.S.C. § 121. These provisions entitle a divisional application filed as the result of a restriction requirement (a Patent Office determination that an applicant has filed claims directed to more than one invention) to be exempt from obviousness-type double patenting. These provisions illustrate a Congressional intention, from the legislative history of the 1952 Patent Act, to prevent the unfairness of forcing an applicant to be required to file a divisional application based on claiming "independent inventions" through restriction while permitting the original application to be used as "prior art" in a obviousness-type double patenting rejection. The Federal Circuit noted, however, that Congress also evinced the intention to restrict the safe harbor to divisional applications (which have an identical specification to the originally-filed application) and keep any claims in such a divisional application strictly within the bounds of what had been determined to be a separate invention. This intention meant, for example, that an applicant would not be able to include claims in a divisional that were within the scope of any claims previously elected for examination. In this way applicants would be precluded from inequitably increasing patent term while not being penalized for electing one invention and pursuing additional inventions in divisional applications.

The Federal Circuit found that the ‘068 application did not fall within the safe harbor because it was a continuation-in-part application, not a divisional. Such a "CIP" application by definition contains some of the disclosure of an earlier-filed application in addition to new disclosure. Because of this distinction, the Federal Circuit found that CIP applications could not fall within the safe harbor because they could encompass additional information (and patentable inventions) that were not a part of the original, restricted claims.

In this case, however, the CAFC has applied the rubric to the application rather than to the claims. A review of the claims of the ‘165 patent, as originally filed, shows that the application contains a claim (claim 29) that recites the same method as the ‘068 patent and a list of species of the generic formula, expressly reciting celecoxib. This claim was subjected to a restriction requirement and the applicants elected to forego prosecution of these method claims until filing the CIP application that resulted in the ‘068 patent. However, the specification of the ‘068 patent is much more extensive than the earlier-filed ‘823 and ‘165 patents; in particular, the ‘068 patent specifically discloses celecoxib synthesis, and contains biological data relating to the specificity of celecoxib for COX2 over COX1 (the biological basis for its advantages as an anti-inflammatory agent). Without specifying any rationale other than the noted distinction between divisional and CIP applications, it appears that these differences in the specification may provide additional support for the Federal Circuit’s determination.

The CAFC upheld the District Court’s determination that claim 9 of the ‘823 patent and claim 17 of the ‘165 patent (directed specifically to celecoxib) were not invalid for failure to satisfy the best mode requirement of 35 U.S.C. § 112, first paragraph. Teva contended that Pfizer’s failure to disclose the COX2 specificity of the claimed compounds was a violation because it prevented the skilled worker from appreciating which of the disclosed compounds exhibited the specificity for COX2. In Teva’s view, this failure of disclosure was significant, because the capacity to block the action of COX2, related to pain, while not inhibiting COX1, related to normal processes such as gastrointestinal integrity, was an important feature of the claimed invention. The Federal Circuit adopted the view of the District Court that Pfizer was under no obligation to disclose this distinction. (Presumably, this would not have been the case if the claim was to a method or included the COX enzyme specific limitations.) Disclosing how to make and use the compounds of the invention was enough to satisfy the best mode requirement. Interestingly, the CAFC noted that while Teva had raised the defense of invalidity against Pfizer’s claims, it had not counterclaimed for a declaratory judgment of invalidity; thus, since claim 9 of the ‘823 patent and claim 17 of the ‘165 patent satisfied the best mode requirement and were infringed, it did not need to reach the "difficult issue" raised by the generic claims. This dicta from the Federal Circuit would seem to raise a caution for similar instances where generic claims are asserted.

Finally, the Federal Circuit found that while the references cited by Teva in its inequitable conduct allegation were material (despite the fact that they would not have constituted invalidating prior art), the CAFC found that Pfizer had rebutted any evidence of intent proffered by Teva. This rebuttal was evidence that the structure of the core heterocyclic ring in the two prior art references was different from the core heterocyclic ring of Pfizer’s patented compounds, and that Pfizer consistently used such distinctions in determining whether prior art was relevant "in hundreds of its other patent applications." The Federal Circuit also credited testimony on this point by a Pfizer witness, that Pfizer had considered these references and had come to a good-faith determination that they were not material to patentability. The CAFC cited its own three-prong test for inequitable conduct enunciated in Ferring B.V. v. Barr Labs., Inc. (Fed. Cir. 2006):

(1) the applicant knew of the information;
(2) the applicant knew or should have known of the materiality of the information; and
(3) the applicant has not provided a credible explanation for the withholding.

Here, Teva’s failure to establish or rebut the third prong was fatal to its inequitable conduct allegation.

As a consequence of the Federal Circuit’s holding the ‘068 patent invalid, the expiration date for the remaining Orange Book listed patents is now May 30, 2014 (when pediatric exclusivity for the ‘165 patent expires) rather than June 2, 2015. Undoubtedly this means millions of dollars in revenue lost, especially since the ‘823 patent was deemed ineligible for patent term extension under 35 U.S.C. § 156.

Pfizer, Inc. v. Teva Pharmaceuticals USA, Inc. (Fed. Cir. 2008)
Panel: Chief Judge Michel, Circuit Judge Dyk, and District Judge Kennelly
Opinion by Circuit Judge Dyk

Additional information regarding this case can be found at Patently-O and the Orange Book Blog.
USPTO News: Patent Office Publishes Notice Regarding Impact of Proposed Markush Claims Rules on Small Entities

March 10, 2008

By Christopher P. Singer —

As we reported on Friday, the U.S. Patent and Trademark Office published a "Proposed Rules" Notice entitled "Examination of Patent Applications That Include Claims Containing Alternative Language," (Markush claims) in the March 10, 2008 Federal Register. The Notice did not enact any Final Rule change, but rather provided an analysis of the impact of the proposed change to Markush practice on certain applicants. In particular, the Notice detailed an initial regulatory flexibility analysis (IRFA), performed by the USPTO, regarding the impact of the proposed rule changes specifically on small entity concerns. According to the Patent Office, it "continues to believe that a regulatory flexibility analysis is not required for the Alternative Claims Notice of Proposed Rule Making . . . however, [it] has decided to subject the proposed rules to a regulatory flexibility analysis to provide a further opportunity for comment on the small business impact of the proposed rules."

The Patent Office reiterated that the rationale behind the proposed rule change is to enhance the ability to grant quality patents in a timely manner. The IRFA detailed in the Notice sampled applications from fiscal year 2005 and found that in 95,018 applications filed by small entity applicants, 20,824 applications contained common alternative claim language. As expected, the percentage of applications employing alternative claim language was skewed heavily to the biotechnology and chemical arts.

For purposes of cost analysis, the Office describes four categories of applications which could fall under the proposed new rule: (1) applications with acceptable alternative claim language (no costs); (2) applications with multiple inventions in a single claim (divisional application costs); (3) applications with improper claim format (amendment costs); and (4) applications with multiple inventions in a single claim and improper claim format (divisional and amendment costs). Not surprisingly, the Patent Office concludes from its estimates that 82 percent of small entity applications in the biotech and chemical arts and 98 percent of small entity applications in the electrical and mechanical arts would not incur any notable incremental costs associated with the rule change.

Written comments on the IRFA or Alternative Claims Notice of Proposed Rule Making must be received on or before April 9, 2008. Comments relating to the IRFA presented in the recent notice are preferably sent by e-mail to markush-irfa.comments@uspto.gov, and comments on the proposed rule changes in the Alternative Claims Notice of Proposed Rule Making should be addressed to markush.comments@uspto.gov. Comments may also be submitted by mail to:

Mail Stop Comments–Patents
Commissioner for Patents
P.O. Box 1450
Alexandria, VA 22313-1450

As another alternative, comments will be accepted by facsimile: (571) 273-7754, to the attention of Kathleen Kahler Fonda, Legal Advisor, Office of Patent Legal Administration. Comments will be made available for public inspection, so information that commentors do not wish to be made public, such as personal information, should not be included in the comments.
Regents of the Univ. of California v. DakoCytomation California, Inc. (Fed. Cir. 2008)

March 9, 2008

By Donald Zuhn —

On February 28th, the Federal Circuit, in Regents of the Univ. of California v. DakoCytomation California, Inc.: (a) affirmed the denial by the District Court for the Northern District of California of a preliminary injunction sought by the Regents of the University of California, Abbott Molecular Inc., and Abbott Laboratories Inc. (Appellants), (b) affirmed in part the District Court’s grant of summary judgment of noninfringement as to U.S. Patent No. 6,596,479, (c) reversed in part the District Court’s grant of summary judgment of noninfringement as to U.S. Patent No. 5,447,841, (d) affirmed the District Court’s construction of "heterogeneous mixture of labeled unique sequence nucleic acid fragments," (e) reversed the District’s Court’s construction of "morphologically identifiable cell nucleus," and (f) reversed the District Court’s determination that Appellants were estopped from asserting that Dako’s products meet a limitation of the ‘841 patent under the doctrine of equivalents. The Federal Circuit remanded the case to the District Court.

The ‘841 and ‘479 patents, which are owned by the Regents of the University of California and are exclusively licensed by Abbott, are directed to improved methods for identifying and classifying chromosomes in order to detect chromosomal abnormalities. The improved methods of the ‘841 and ‘479 patents seek to overcome two problems that existed in the prior art: (1) the requirement of prior art methods that chromosomes be in the metaphase stage of the cell-division cycle (when the chromosomes are condensed and microscopically visible) as opposed to the interphase stage (when the chromosomes are not condensed and therefore not microscopically visible), and (2) the nonspecificity of prior art methods that use nucleic acid probes to detect particular chromosomal sequences, which leads to unacceptable false-positive results. This nonspecificity is caused by the hybridization of the nucleic acid probes to repetitive nucleotide sequences scattered throughout the chromosomes; in effect, the repetitive sequences "interfere" with the ability of the nucleic acid probes to hybridize only with particular chromosomal sequences.

The claimed methods of the ‘841 and ‘479 patents overcome the problems in the prior art by eliminating the "interference" caused by repetitive sequences. In the methods of the ‘841 patent, the interference is eliminated by blocking repetitive sequences, and in the methods of the ‘479 patent, the interference is eliminated by removing the repetitive sequences. In particular, in the methods of the ‘841 patent, "blocking nucleic acid . . . fragments which are substantially complementary to repetitive segments" are added to "labeled nucleic acid . . . fragments which are substantially complementary to nucleic acid segments within the chromosomal DNA for which detection is desired," and in the methods of the ‘479 patent, "a heterogeneous mixture of labeled unique sequence nucleic acid fragments which are substantially complementary to nucleic acid segments within the interphase chromosomal DNA for which detection is desired" is used.

In September of 2005, Appellants brought suit against Dako for patent infringement, and then in October of 2005 filed a motion for preliminary injunction seeking to enjoin Dako from manufacturing and selling its HER2 kit. Based on the District Court’s construction of the limitations "morphologically identifiable chromosome or cell nucleus" and "heterogeneous mixture of labeled unique sequence nucleic acid fragments" of the ‘479 patent, and its conclusion that Dako’s product did not meet the "blocking nucleic acid" limitation of the ‘841 patent under the doctrine of equivalents, the District Court determined that Appellants had failed to show a likelihood of success on the merits with respect to their infringement claims, and therefore denied Appellants’ motion.

The District Court subsequently issued a second order, amending the basis for its denial of Appellants’ preliminary injunction motion. In particular, the District Court maintained its rejection of Appellants’ proposed construction of "heterogeneous mixture of labeled unique sequence nucleic acid fragments," but on the grounds that adopting such a construction would render the ‘479 patent invalid under the doctrine of obviousness-type double patenting (the District Court had previously determined that adopting Appellants’ construction, which only appears in the ‘479 patent, would render the ‘479 patent invalid in view of the ‘841 patent, which the Court determined to be prior art to the ‘479 patent). Appellants appealed both orders to the Federal Circuit.

While these appeals were pending, Dako moved for summary judgment of noninfringement. Following a Markman hearing, the District Court granted summary judgment of noninfringement as to the ‘479 patent based on the Court’s construction of the "heterogeneous mixture of labeled unique sequence nucleic acid fragments" limitation, and granted summary judgment of noninfringement as to the ‘841 patent based on the Court’s conclusion that Appellants were barred from asserting that two of Dako’s products met the "blocking nucleic acid" limitation under the doctrine of equivalents (the Court denied summary judgment as to the ‘841 patent for twenty other Dako products). Following the District Court’s order, the parties filed a joint motion to certify for immediate appeal, which the District Court granted, and the Federal Circuit then granted permission to appeal the interlocutory order.

On appeal, Appellants argued that the District Court had erred in: (1) construing the limitation "heterogeneous mixture of labeled unique sequence nucleic acid fragments," (2) applying prosecution history estoppel to the "blocking nucleic acid" limitation, and (3) construing the limitation "morphologically identifiable cell nucleus." With respect to the first issue, Appellants argued that the District Court erred in construing the limitation to mean that the heterogeneous mixture excludes repetitive sequences (Dako’s kits contain repetitive sequences). Appellants based their argument on the doctrine of claim differentiation (some of the patent’s dependent claims require repetitive sequences) and the District Court’s improper reliance on the prosecution history (Appellants asserted that the term "unique sequence" was added during prosecution to clarify that the claimed method was related to the detection — and not necessarily use — of unique sequences).

Despite finding that the District Court erred in first concluding that the ‘841 patent was prior art to the ‘479 patent and then concluding that the ‘479 patent would be rendered invalid due to obviousness-type double patenting, the Federal Circuit affirmed the District Court’s construction of the heterogeneous mixture limitation as well as the District Court’s determination that some of Dako’s kits contain repetitive sequences, and therefore, do not infringe the ‘479 patent. The basis of the Federal Circuit’s affirmance was Appellants’ ability to overcome an enablement rejection (the examiner argued that a mixture containing repetitive sequences would not work due to nonspecific hybridization) by limiting the heterogeneous mixture’s composition to unique sequences. As for Appellants’ claim differentiation argument, the Federal Circuit noted that "the presumption created by the doctrine of claim differentiation is ‘not a hard and fast rule and will be overcome by a contrary construction dictated by the written description or prosecution history.’"

With respect to the "blocking nucleic acid" limitation, Appellants argued that the District Court erred in barring them from asserting that the peptide nucleic acids (PNAs) used in Dako’s kits were an equivalent of the blocking nucleic acids recited in the claims (the parties had stipulated that the "nucleic acid" portion of the term was limited to DNA and RNA). In particular, Appellants asserted that since the "blocking nucleic acid" limitation was never narrowed during prosecution, the District Court improperly applied the doctrine of prosecution history.

The Federal Circuit concluded first that "[b]ecause the prosecution history suggests that the patentees limited the claim to the blocking method at least in part to overcome the examiner’s rejections, the patentees presumptively surrendered all equivalents of the ‘blocking nucleic acid’ limitation." The CAFC then concluded that Appellants "met their burden of showing that the amendment did not surrender the equivalent in question because the narrowing amendment was only tangential to the accused PNA equivalent," and therefore, determined that the District Court erred in finding that Appellants were estopped from asserting that Dako’s products infringe under the doctrine of equivalents. The Federal Circuit based its conclusion on the fact that when the patentees amended the claims to add the "blocking nucleic acid" limitation, they "argued that that the invention was new and nonobvious because it used the blocking method in connection with in situ hybridization for the detection of unique sequences" (emphasis added). Thus, the CAFC concluded that Appellants’ narrowing amendment focused on the "blocking" aspect and not on the "nucleic acid" aspect of the limitation. The Federal Circuit, therefore, reversed the District Court’s determination that Appellants were barred from asserting that Dako’s PNA-containing kits infringed under the doctrine of equivalents.

Finally, with respect to the "morphologically identifiable cell nucleus" limitation, Appellants argued that the District Court erred in construing the term to mean "a single cell nucleus that contains the full complement of chromosomal DNA." Appellants asserted that the limitation "merely requires that the nucleus be ‘capable of being identified by its form or function’ and does not require the full set of DNA." The Federal Circuit agreed with Appellants, stating that "[s]ignificantly, nowhere in the prosecution history, or the specification for that matter, do we find any indication that the ‘morphologically identifiable’ language was added to impose a requirement that the cell nucleus must retain its full complement of chromosomal DNA." The CAFC, therefore, determined that the District Court erred in construing this limitation.

Judge Prost dissented with respect to the portion of the majority opinion that holds that the doctrine of equivalents is not precluded by prosecution history estoppel because the tangential exception applies, writing that the majority’s finding "is contrary to this court’s precedent and to the proper application of prosecution history estoppel as set forth by the Supreme Court." Citing Norian Corp. v. Styker Corp., Judge Prost noted that:

[I]t frequently happens that patentees surrender more through amendment than may have been absolutely necessary to avoid particular prior art. In such cases, we have held the patentees to the scope of what they ultimately claim, and we have not allowed them to assert that claims should be interpreted as if they had surrendered only what they had to.

Observing that the patentees narrowed the scope of the claims from any method of eliminating interference from repetitive sequences to just the use of "blocking nucleic acid," Judge Prost stated that:

It is irrelevant to the determination of the scope of the surrendered territory that to overcome the prior art references the patentee did not need to amend the claims to a method of disabling the hybridization capacity of repetitive sequences by blocking with a "blocking nucleic acid," but instead could have amended the claims to a method of disabling repetitive sequences by blocking.

Judge Prost concluded that:

To overcome the presumption of prosecution history estoppel "[t]he patentee must show that at the time of the amendment one skilled in the art could not reasonably be expected to have drafted a claim that would have literally encompassed the alleged equivalent." Here, the appellants could reasonably have been expected to have drafted a claim that encompassed blocking repetitive sequences using PNA. The appellants should, therefore, be estopped from asserting that PNA is an equivalent to "blocking nucleic acid" in the ‘841 patent.

Regents of the Univ. of California v. DakoCytomation California, Inc. (Fed. Cir. 2008)
Panel: Circuit Judges Mayer, Lourie, and Prost
Opinion by Circuit Judge Lourie; opinion dissenting-in-part by Circuit Judge Prost

Additional information regarding this case can be found at Patently-O.
Court Report

March 9, 2008

By Sherri Oslick —

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

Duramed Pharmaceuticals, Inc. v. Watson Laboratories, Inc. et al.
3:08-cv-00116; filed March 6, 2008 in the District Court of Nevada

Duramed Pharmaceuticals, Inc. v. Watson Laboratories, Inc. et al.
2:08-cv-01145; filed March 4, 2008 in the District Court of New Jersey

Infringement of U.S. Patent No. 7,320,969 ("Oral Contraceptives to Prevent Pregnancy and Diminish Premenstrual Symptomatology," issued January 22, 2008) following a paragraph IV certification as part of Watson’s filing of an ANDA to manufacture a generic version of Duramed’s Seasonique® (levonorgestrel/ethinyl estradiol, used as oral contraception). The complaints in these cases are substantially identical. View the New Jersey complaint here.

Watson Laboratories Inc v. Duramed Pharmaceuticals Inc et al.
8:08-cv-00243; filed March 4, 2008 in the Central District of California

Declaratory judgment of non-infringement and/or invalidity of U.S. Patent No. 7,320,969 ("Oral Contraceptives to Prevent Pregnancy and Diminish Premenstrual Symptomatology," issued January 22, 2008) in conjunction with Watson’s filing of an ANDA to manufacture a generic version of Duramed’s Seasonique® (levonorgestrel/ethinyl estradiol, used as oral contraception). View the complaint here.

Mylan Pharmaceuticals Inc. v. Eli Lilly and Company
3:08-cv-00144; filed March 4, 2008 in the Eastern District of Virginia

Declaratory judgment of non-infringement, unenforceabilty and/or invalidity of U.S. Patent No. 5,658,590 ("Treatment of Attention-Deficit/ Hyperactivity Disorder," issued August 19, 1997) in conjunction with Mylan’s filing of an ANDA to manufacture a generic version of Lilly’s Strattera® (atomoxetine hydrochloride, used to treat attention-deficit/hyperactivity disorder). View the complaint here. [NB: This case was voluntarily dismissed by Mylan two days after filing.]

Abbott Laboratories et al. v. Teva Pharmaceuticals USA, Inc.
1:08-cv-01243; filed February 29, 2008 in the Northern District of Illinois

Infringement of U.S. Patent Nos. 6,277,405 ("Fenofibrate Pharmaceutical Composition Having High Bioavailability and Method for Preparing It," issued August 21, 2001), 7,037,529 (same title, issued May 2, 2006), and 7,041,319 ("Fenofibrate Pharmaceutical Composition Having High Bioavailabilty," issued May 9, 2006) following a paragraph IV certification as part of Teva’s filing of an ANDA to manufacture a generic version of Abbott’s Tricor® (fenofibrate, used in the treatment of increased triglyceride levels). View the complaint here.

Elan Pharma International Ltd. et al. v. Teva Pharmaceuticals USA, Inc.
2:08-cv-01085; filed February 29, 2008 in the District Court of New Jersey

Infringement of U.S. Patent Nos. 5,145,684 ("Surface Modified Drug Nanoparticles," issued September 8, 1992), 7,276,249 ("Nanoparticulate Fibrate Formulations," issued October 2, 2007), and 7,320,802 ("Methods of Treatment Using Nanoparticulate Fenofibrate Compositions," issued January 22, 2008), all licensed to Abbott, following a paragraph IV certification as part of Teva’s filing of an ANDA to manufacture a generic version of Abbott’s Tricor® (fenofibrate, used in the treatment of increased triglyceride levels). View the complaint here.
Conference & CLE Calendar

March 9, 2008

March 12, 2008 – Biotechnology, Chemical & Pharmaceutical Art Group Customer Partnership Meeting (U.S. Patent and Trademark Office)

March 17, 2008 – Recent Decisions: How They Affect Your Corporate IP Practice (Intellectual Property Owners Association) – Arlington, VA

March 30-April 1, 2008 – Advanced Courses (Patent Resources Group) – Bonita Springs, FL

March 31-April 1, 2008 – Document Management, E-Discovery, and Litigation Readiness (American Conference Institute) – New York, NY

April 3-5, 2008 – Advanced Courses (Patent Resources Group) – Bonita Springs, FL

April 7, 2008 – Successful Mulitlateral Patents (Law Seminars International) – Arlington, VA

April 10-12, 2008 – 23rd Annual Intellectual Property Law Conference (American Bar Association) – Arlington, Virginia

April 25, 2008 – Patent Claim Construction (Law Seminars International) – Atlanta, GA

April 30-May 1, 2008 – Pharma/Biotech Collaborative Agreements (American Conference Institute) – San Francisco, CA

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

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

***Patent Docs is a media sponsor of this conference or CLE.
USPTO News: Federal Register Notice Regarding Markush Claims to Publish on Monday March 10, 2008

March 7, 2008

By Christopher P. Singer —

According to the Office of the Federal Register (OFR), a Notice will publish on Monday, March 10, 2008 relating to "Examination of Patent Applications That Include Claims Containing Alternative Language" (i.e., Markush claim language). While the Notice is currently styled as "Proposed Rules," we note that the U.S. Patent and Trademark Office previously published proposed rules regarding this topic, and requested public comment, in August 2007.

While the final form (and status) of these rules is not known, the originally-published version was designed to "require applicants to identify, with more specificity, the claimed invention to be examined, thus promoting examination quality." Patent Docs will provide an overview of this Notice on Monday.

For additional information on this topic, please see:

• "USPTO’s Bruce Kisliuk Addresses ACI Conference," March 3, 2008
• "IPO Releases Comments on New Markush Rules," October 30, 2007
• "Patent Office Proposes New Rules for Alternative Claiming," August 12, 2007

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